The research,fabrication and development of piezoelectric nanofibrous materials offer effective solutions to the challenges related to energy consumption and non-renewable resources.However,enhancing their electrical ...The research,fabrication and development of piezoelectric nanofibrous materials offer effective solutions to the challenges related to energy consumption and non-renewable resources.However,enhancing their electrical output still remains a significant challenge.Here,a strategy of inducing constrained phase separation on single nanofibers via shear force was proposed.Employing electrospinning technology,a polyacrylonitrile/polyvinylidene difluoride(PAN/PVDF)nanofibrous membrane was fabricated in one step,which enabled simultaneous piezoelectric and triboelectric conversion within a single-layer membrane.Each nanofiber contained independent components of PAN and PVDF and exhibited a rough surface.The abundant frictional contact points formed between these heterogeneous components contributed to an enhanced endogenous triboelectric output,showcasing an excellent synergistic effect of piezoelectric and triboelectric response in the nanofibrous membrane.Additionally,the component mass ratio influenced the microstructure,piezoelectric conformation and piezoelectric performance of the PAN/PVDF nanofibrous membranes.Through comprehensive performance comparison,the optimal mass ratio of PAN to PVDF was determined to be 9∶1.The piezoelectric devices made of the optimal PAN/PVDF nanofibrous membranes with rough nanofiber surfaces generated an output voltage of 20 V,which was about 1.8 times that of the smooth one at the same component mass ratio.The strategy of constrained phase separation on the surface of individual nanofibers provides a new approach to enhance the output performance of single-layer piezoelectric nanofibrous materials.展开更多
Ship outfitting is a key process in shipbuilding.Efficient and high-quality ship outfitting is a top priority for modern shipyards.These activities are conducted at different stations of shipyards.The outfitting plan ...Ship outfitting is a key process in shipbuilding.Efficient and high-quality ship outfitting is a top priority for modern shipyards.These activities are conducted at different stations of shipyards.The outfitting plan is one of the crucial issues in shipbuilding.In this paper,production scheduling and material ordering with endogenous uncertainty of the outfitting process are investigated.The uncertain factors in outfitting equipment production are usually decision-related,which leads to difficulties in addressing uncertainties in the outfitting production workshops before production is conducted according to plan.This uncertainty is regarded as endogenous uncertainty and can be treated as non-anticipativity constraints in the model.To address this problem,a stochastic two-stage programming model with endogenous uncertainty is established to optimize the outfitting job scheduling and raw material ordering process.A practical case of the shipyard of China Merchants Heavy Industry Co.,Ltd.is used to evaluate the performance of the proposed method.Satisfactory results are achieved at the lowest expected total cost as the complete kit rate of outfitting equipment is improved and emergency replenishment is reduced.展开更多
The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate ne...The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.展开更多
Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
There are two formation routes of dietary N-nitrosamines:exogenous and endogenous formation.The formation of N-nitrosamines from either source requires precursors with a dialkylamine functional group and a nitrosating...There are two formation routes of dietary N-nitrosamines:exogenous and endogenous formation.The formation of N-nitrosamines from either source requires precursors with a dialkylamine functional group and a nitrosating agent.Precursors are supplied primarily by amine-rich foods and nitrosating agents are nitrite or its reaction products(N_(2)O_(3) and NO^(+)).Unprocessed fresh foods initially contain zero or only trace amounts of N-nitrosamines while significant amounts of N-nitrosamines can be generated during certain types of food processing.Cooking methods,pH,additives,and storage conditions can affect the formation of N-nitrosamines in foods.We analysed the formation mechanisms/pathways of the three most frequently detected N-nitrosamines in processed meats.Formation of endogenous N-nitrosamines is likely to be greater than that of exogenous N-nitrosamines.Nitrosating agents involved in the formation of endogenous N-nitrosamines are formed from nitrate in vegetables via the nitrate-nitrite-NO cycle.N-nitrosamines are produced in the human stomach and intestine but their formation mechanisms differ.We analysed the mechanism/pathway for the formation of N-nitrosotryptophan from tryptophan in the stomach.The formation of N-nitrosamines in the intestine includes both chemical and microbiological mechanisms.In addition to N-nitrosation,S-nitrosation also occurs in the human body.There is a competitive relationship between the two reactions,and S-nitrosation is more likely to occur in the healthy human body.This paper reviews the mechanisms and factors influencing the formation of exogenous and endogenous dietary N-nitrosamines,which illustrate the importance of microbial-mediated N-nitrosamine formation and the production of endogenous N-nitrosamines.展开更多
Drought is one of the important stress factors affecting the growth and development processes of wheat in China's arid zones, which severely limits the yield. This study examined the impact of deficit irrigation o...Drought is one of the important stress factors affecting the growth and development processes of wheat in China's arid zones, which severely limits the yield. This study examined the impact of deficit irrigation on the flag leaf protection system and yield of drip-irrigated spring wheat during the growth stages in arid zones. In addition, this study aimed to determine the optimal water supply mode for efficient production under drip irrigation conditions and to provide technical support for water-saving and high-yield cultivation of drip-irrigated wheat. The experiment was conducted with a split plot design using the water-sensitive variety Xinchun 22(XC22) and the drought-tolerant variety Xinchun 6(XC6) as the main plots, while a fully irrigated control(CK, 75–80% FC, where FC is field water holding capacity), mild deficit(T1, 60–65% FC) and moderate deficit(T2, 45–50% FC) at the tillering stage, and mild deficit(J1, 60–65% FC) and moderate deficit(J2, 45–50% FC) at the jointing stage were used as the subplots. Systematic studies were conducted on the regulatory effects of deficit irrigation during the tillering and jointing stages on protective substances, membrane lipid metabolism, endogenous hormones in the flag leaf, and yield of spring wheat. Compared with treatments T2 and J2, treatments T1 and J1 were beneficial for increasing the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT), the levels of proline(Pro), indole-3-acetic acid(IAA), and zeatin riboside(ZR), and the ratios IAA/abscisic acid(ABA), ZR/ABA, IAA/ZR, and(IAA+ZR)/ABA, while reducing the levels of hydrogen peroxide(H2O2), superoxide anion radicals(O2–·), malondialdehyde(MDA), phosphatidic acid(PA), free fatty acids(FFA), ABA, phospholipase D(PLD), and lipoxygenase(LOX), alleviating flag leaf senescence, and increasing yield. Under treatment T1, the SOD, POD, CAT, and Pro levels of flag leaves in XC6 were 11.14, 8.08, 12.98, and 3.66% higher than those of treatment CK, and under treatment J1, they were 6.43, 4.49, 7.36, and 2.50% higher than those of treatment CK. Under treatment T1 in XC6, the IAA, ZR level of the flag leaf, spike number, grains per spike, 1,000-grain weight and yield were 10.50, 5.79, 3.10, 8.84, 3.78, and 10.52% higher than those of treatment CK, and under treatment J1, they were 5.36, 3.94, 2.40, 3.72, 1.37, and 4.46% higher than those of treatment CK. Compared with XC22, XC6 was more conducive to the improvement of flag leaf protective substances, IAA, ZR, dry matter weight, yield components and yield. The correlation analysis showed significant positive correlations between IAA and ZR with SOD, POD, CAT, proline, and yield. IAA and ZR promoted the enhancement of protective enzyme activities, thereby clearing reactive oxygen species to cope with the oxidative stress caused by drought and achieve the effect of delaying senescence. Principal component analysis showed that yield components and dry matter weight, had direct effects on yield. Mild deficiency during the tillering stage without water stress in other stages could effectively optimize yield components, not only achieving high yield while increasing protective substances, but also reducing the reactive oxygen species content. This strategy can be recommended as a water-saving and high-yield production mode for drip irrigation of spring wheat in Xinjiang, China.展开更多
BACKGROUND Insulin therapy plays a crucial role in managing diabetes.Regulatory guidelines mandate assessing the pharmacokinetics(PK)and pharmacodynamics(PD)of new insulin formulations with euglycemic clamp techniques...BACKGROUND Insulin therapy plays a crucial role in managing diabetes.Regulatory guidelines mandate assessing the pharmacokinetics(PK)and pharmacodynamics(PD)of new insulin formulations with euglycemic clamp techniques before entry into the market.Typically,blood glucose(BG)levels are maintained at 5%below baseline to suppress endogenous insulin secretion in healthy volunteers.However,in scenarios where BG baseline is relatively low,maintaining it at 5%below baseline can increase hypoglycemic risk.Consequently,we adjusted to maintain it at 2.5%below a baseline of<4.00 mmol/L.It remains uncertain whether this adjustment impacts endogenous insulin inhibition or the PD of study insulin.AIM To evaluate and compare the PD and C-peptide status using two different target BG setting methods.METHODS Data came from euglycemic clamp trials assessing the PK/PD of insulin aspart(IAsp)in healthy participants.Target BG was set at 2.5%below baseline for those with a basal BG of<4.00 mmol/L(group A),and at 5%below baseline for others(group B).The area under the curve(AUC)of IAsp(AUC_(IAsp,0-8 h))and GIR from 0 to 8 hours(AUCGIR,0-8 h)was used to characterize the PK and PD of IAsp,respectively.The C-peptide reduction and PK/PD of IAsp were compared between the two groups.RESULTS Out of 135 subjects,15 were assigned to group A and 120 to group B;however,group B exhibited higher basal Cpeptide(1.59±0.36 vs 1.32±0.42 ng/mL,P=0.006).Following propensity score matching to adjust for basal Cpeptide differences,71 subjects(15 in group A and 56 in group B)were analyzed.No significant differences were observed in demographics,IAsp dosage,or clamp quality.Group B showed significantly higher baseline(4.35±0.21 vs 3.91±0.09 mmol/L,P<0.001),target(4.13±0.20 vs 3.81±0.08 mmol/L,P<0.001),and clamped(4.10±0.17 vs 3.80±0.06 mmol/L,P<0.001)BG levels.Both groups exhibited comparable C-peptide suppression(32.5%±10.0%vs 35.6%±12.1%,P=0.370)and similar IAsp activity(AUCGIR,0-8 h:1433±400 vs 1440±397 mg/kg,P=0.952)under nearly equivalent IAsp exposure(AUC_(IAsp,0-8 h):566±51 vs 571±85 ng/mL×h,P=0.840).CONCLUSION Maintaining BG at 2.5%below a baseline of<4.00 mmol/L did not compromise the endogenous insulin suppression nor alter the observed pharmacodynamic effects of the study insulin.展开更多
Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within t...Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.展开更多
[Objectives]This study was conducted to investigate the regulatory effects of selenium(Se)on the content and balance of endogenous hormones and the function of antioxidant system during seed development in Red sandalw...[Objectives]This study was conducted to investigate the regulatory effects of selenium(Se)on the content and balance of endogenous hormones and the function of antioxidant system during seed development in Red sandalwood(Pterocarpus santalinus).[Methods]Two basic treatments,seven single-fertilization treatments,and four combined fertilization treatments were designed.Sampling was conducted at 2,5,8,and 18 weeks after flower withering to measure the embryo abortion percentage(EAP),the contents of three endogenous hormones(IAA,GA_(3),ABA),and the activities of four antioxidant enzymes(CAT,APX,SOD,GR).[Results]Se application significantly inhibited embryo abortion in Red sandalwood,with Na_(2)SeO_(3)[Se(IV)]showing superior effects to Na_(2)SeO_(3)(Se(VI))and far exceeding the efficacy of individual applications of KCl,H_(3)BO_(3),CO(NH_(2))_(2),Ca(H_(2)PO_(4))_(2),NPK compound fertilizer,or EFOF.The combined treatment of Se with NPK compound fertilizer and EFOF[EFOF+NPK compound fertilizer+Se(IV)]was the most effective,reducing the abortion percentage by 77.8%compared with UMC at 18 weeks after flower withering.Se application significantly increased the levels of three endogenous hormones and the(IAA+GA_(3))/ABA ratio in Red sandalwood seeds(including the embryonic stage).In the optimal treatment,the(IAA+GA_(3))content was 240.7%,256.4%,353.7%,and 502.9%higher than that of UMC at 2,5,8,and 18 weeks after flower withering,respectively.Se application also concurrently enhanced antioxidant enzyme activities,with all four antioxidant enzymes in seeds of Se-treated plants showing significant increases.Notably,the selenoenzyme GR maintained considerably high activity even at 18 weeks after flower withering.The EAP was highly significantly negatively correlated with IAA content and GR activity,identifying IAA and(IAA+GA_(3))content as key hormonal indicators and GR as the core antioxidant enzyme,together constituting the central regulatory factors.The results indicate that Se suppresses embryo abortion in Red sandalwood through a dual regulatory pathway:by elevating IAA and GA_(3)levels along with the(IAA+GA_(3))/ABA ratio to optimize hormonal signaling networks,and by enhancing the activities of antioxidant enzymes such as GR to alleviate oxidative stress induced by cool-season low temperatures.[Conclusions]This study provides a theoretical basis and technical strategy for precision fertilization and stress resistance management in the cultivation of Red sandalwood.展开更多
AIM:To report the demographic and systemic characteristics of patients,clinical progression of endophthalmitis,and the efficacy of various treatment strategies,with a focus on identifying key factors for preserving vi...AIM:To report the demographic and systemic characteristics of patients,clinical progression of endophthalmitis,and the efficacy of various treatment strategies,with a focus on identifying key factors for preserving vision in eyes with endogenous endophthalmitis due to Klebsiella pneumoniae(K.pneumoniae)liver abscess.METHODS:In this single-center,retrospective case series of 18 patients with endogenous endophthalmitis due to K.pneumoniae liver abscess were analyzed.Ophthalmologic features of endophthalmitis at early,intermediate and advanced stages were obtained from eyes with endophthalmitis of different severities.Prompt vitrectomy was considered primarily for all eyes except for very early endophthalmitis.Intravitreal injections of antibiotics were performed in eyes with endophthalmitis in the very early stages and in eyes where vitrectomy was not available,and additional control of infection was needed after vitrectomy.Evisceration was performed in eyes with corneoscleral perforation,advanced endophthalmitis,perforation with preseptal or orbital cellulitis,uncontrolled infection,or severe pain with no vision.RESULTS:Mean(±standard deviation)age of the 18 patients with endophthalmitis was 64.5±12.2(range:32-84)y,and 14 patients(77.8%)were males.Endophthalmitis tended to involve the retinal parenchyma first and then progressed into the vitreous cavity and anterior segments.However,it presented a tendency to cause massive subretinal abscesses even after vitrectomy with silicone oil tamponade.Very high intraocular pressure with new vessels on the iris(41.7%)were also commonly observed.Although all but three patients had systemic disease such as diabetes or hypertension,visual prognosis after treatment did not appear to depend significantly on underlying comorbidities.A final best-corrected visual acuity better than 20/60 was achieved only when lesions were detected very early,with relatively good initial visual acuity,likely reflecting lower bacterial inoculation in the eye.CONCLUSION:Detection of early endophthalmitis lesions appears to be the only way to preserve good vision in patients with K.pneumoniae liver abscesses.Therefore,proper guidelines for ophthalmologic screening remain to be established for subjects at a high risk of endophthalmitis.展开更多
The phenomenon of fear memory generalization can be defined as the expansion of an individual's originally specific fear responses to a similar yet genuinely harmless stimulus or situation subsequent to the occurr...The phenomenon of fear memory generalization can be defined as the expansion of an individual's originally specific fear responses to a similar yet genuinely harmless stimulus or situation subsequent to the occurrence of a traumatic event[1].Fear generalization within the normal range represents an adaptive evolutionary mechanism to facilitate prompt reactions to potential threats and to enhance the likelihood of survival.展开更多
CRISPR-based tran-scription regulators(CRISPR-TRs)have revolutionized the field of synthetic biol-ogy by enabling tar-geted activation or repression of any de-sired gene.However,the majority of exist-ing inducible CRI...CRISPR-based tran-scription regulators(CRISPR-TRs)have revolutionized the field of synthetic biol-ogy by enabling tar-geted activation or repression of any de-sired gene.However,the majority of exist-ing inducible CRISPR-TRs are limited by their dependence on specific sequences,which restricts their flex-ibility and controllability in genetic engineering applications.In this study,we proposed a novel strategy to construct sequence-independent inducible CRISPR-TRs,which is achieved by the design of stem loop 2 in the single guide RNA(sgRNA).Under this strategy,by utiliz-ing toehold-mediated strand displacement(TMSD)reactions between small endogenous molecules(miR-20a and TK1 mRNA)and bridge RNA(bRNA)to link bRNA with sgRNA,we achieved synergistic transcriptional activation of VP64 and p65-HSF1 in response to en-dogenous molecules.To enable response to exogenous molecules,we added response se-quences and bRNA sequences to the 5'end of sgRNA to block sgRNA activity,and achieved activation of sgRNA by shearing the response sequence,called sequential unlimited interlock-ing(SUI).Compared with conventional sequence-restricted interlocking(spacer-blocking hairpin(SBH)),the transcriptional activation ratio between response and non-response to the Cas6A protein using our approach was increased by 2.28-fold.Our work presents a modular and versatile framework for endogenous and exogenous molecule-responsive CRISPR-TRs in mammalian cells,without limitations imposed by sequence dependence.展开更多
This paper provides a systematic review of Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging(MALDI-MSI),encompassing its technical principles,experimental workflows,matrix optimization strategies,a...This paper provides a systematic review of Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging(MALDI-MSI),encompassing its technical principles,experimental workflows,matrix optimization strategies,and recent advancements in plant science applications.It highlights the method's groundbreaking applications in spatial mapping of plant metabolites,dynamic hormone monitoring,and functional studies of tissue microdomains,while offering critical insights into current technical limitations and future research directions.展开更多
The human endogenous retrovirus type W envelope glycoprotein(ERVWE1),located at chromosome 7q21–22,has been implicated in the pathophysiology of schizophrenia.Our previous studies have shown elevated ERVWE1 expressio...The human endogenous retrovirus type W envelope glycoprotein(ERVWE1),located at chromosome 7q21–22,has been implicated in the pathophysiology of schizophrenia.Our previous studies have shown elevated ERVWE1 expression in schizophrenia patients.Growing evidence suggests that autophagy dysfunction contributes to schizophrenia,yet the relationship between ERVWE1 and autophagy remains unclear.In this study,bioinformatics analysis of the human prefrontal cortex RNA microarray dataset(GSE53987)revealed that differentially expressed genes were predominantly enriched in autophagy-related pathways.Clinical data further demonstrated that serum levels of microtubuleassociated protein 1 light chain 3β(LC3B),a key marker of macroautophagy,were significantly elevated in schizophrenia patients compared to controls,and positively correlated with ERVWE1 expression.Cellular and molecular experiments suggested that ERVWE1 promoted macroautophagy by increasing the LC3B II/I ratio,enhancing autophagosome formation,and reducing sequestosome 1(SQSTM1)expression via upregulation of NADPH oxidase activator 1(NOXA1).Concurrently,NOXA1 downregulated the expression of key micromitophagy-related genes,including PTEN-induced kinase 1(PINK1),Parkin RBR E3 ubiquitin-protein ligase(Parkin),and the pyruvate dehydrogenase E1 subunitα1(PDHA1).As a result,ERVWE1,via NOXA1,inhibited micromitophagy by suppressing the expression of PINK1,Parkin,and PDHA1,thereby leading to impaired production of mitochondrialderived vesicles(MDVs).Mechanistically,ERVWE1 enhanced NOXA1 transcription by upregulating upstream transcription factor 2(USF2).In conclusion,ERVWE1 promotes macroautophagy and inhibits micromitophagy through USF2-NOXA1 axis,providing novel mechanistic insight into the role autophagy dysregulation in schizophrenia.These findings suggest that targeting autophagy pathways may offer novel therapeutic strategies for schizophrenia treatment.展开更多
BACKGROUND As a non-coding RNA molecule,circular RNAs(circRNAs)have significant specificity,and existing data suggest a close relationship between them and the prognosis of patients with gastric cancer(GC).However,thi...BACKGROUND As a non-coding RNA molecule,circular RNAs(circRNAs)have significant specificity,and existing data suggest a close relationship between them and the prognosis of patients with gastric cancer(GC).However,this mechanism has no evidence yet.This article explores the functions of hsa_circRNA_102415 in the malignant behavior and potential downstream signaling of GC cells.The chosen approach is loss of signal and functional gain.AIM To investigate and analyze the relationship between hsa_circRNA_102415 and GC and explore its specific role.Results provide reference for other researchers to develop targeted treatment plans.METHODS The gene expression omnibus(GEO)database can be used to obtain the microarray dataset GSE83521.Data were analyzed using the GEO2R tool to identify differences in circRNAs between normal and GC samples.Quantitative real-time polymerase chain reaction was used to detect differentially expressed genes in GC tissue samples and adjacent cancer tissue samples.GC cells were transfected with small interfering-hsa_circRNA_104415 and plasmid DNA(pcDNA)-hsa_ircRNA_102415.Multiple detection methods,such as Transwell and cell counting kit 8,were used to evaluate cellular physiological activities,including cell invasion and proliferation.The relationship between Wnt family members 2B,microRNA(miR)-4529-5p,etc.,including argonaute 2-RNA immunoprecipitation and luciferase reporter genes was analyzed.Rescue experiments were conducted to analyze and explore the relationship between the malignant behavior of GC cells and hsa_circRNA_102415.RESULTS GEO2R analysis confirmed that hsa_circRNA_102415 had significantly higher expression levels in disease tissues.hsa_circRNA_102415 and miR-4529-5p showed a negative correlation in disease cells,suggesting that hsa_circRNA_102415 upregulated WNT2B expression in GC cells as a competing endogenous RNA for miR-4529-5p.miR-4529-5p mimic or small interfering-WNT2B reversed the effects of pcDNA-hsa_circRNA_102415 or miR-4529-5p inhibitor on cell malignant functions.CONCLUSION miR-4529-5p was used to successfully activate the potential of WNT2B,clarify the role of hsa_circRNA_102415 in GC cells,and provide reference for other researchers to develop targeted treatment plans.展开更多
Accurately distinguishing between the endogenous formation and exogenous exposure of Fe-bearing particles(e.g.,magnetic Fe particles)within biological organisms is the prerequisite for scientifically evaluating their ...Accurately distinguishing between the endogenous formation and exogenous exposure of Fe-bearing particles(e.g.,magnetic Fe particles)within biological organisms is the prerequisite for scientifically evaluating their health risks.However,this remains a challenging task due to lacking the comprehensive understanding of the endogenous formation process of Fe-bearing particles.Here,we report the formation dynamics of Fe-bearing particles under conditions closely resembling actual physiological conditions,and compare the morphological and structural differences between endogenous and exogenous Fe-bearing particles.We find that Fe-bearing particles can indeed form under physiological conditions at 37℃.In this process,phosphate plays a crucial role in the oxidation and mineralization of iron ions.Moreover,endogenously formed Fe-bearing particles typically have a diameter of less than8 nm,and iron is the only metal element present.Therefore,we propose that Fe-bearing particles found in the body with a diameter larger than 8 nm are mainly derived from exogenous exposure.For Fe-bearing particles smaller than 8 nm,it is necessary to combine associated elements and crystal structure characteristics to distinguish between endogenous and exogenous sources.This study provides direct evidence from endogenous metabolism for tracing Fe-bearing particles,especially magnetic iron particles,within the human body.展开更多
Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The...Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.展开更多
Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactiv...Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.展开更多
Dry-cured meat products are considerably popular around the world due to unique flavor.Proteolysis is one of the enzymatic reactions from which flavor substances are derived,which is affected by endogenous proteases.T...Dry-cured meat products are considerably popular around the world due to unique flavor.Proteolysis is one of the enzymatic reactions from which flavor substances are derived,which is affected by endogenous proteases.The purpose aimed to reveal the potential relationship between endogenous proteases and key flavor substances in dry-cured pork coppa in this paper.The dynamic changes of endogenous proteases activity,free amino acids,and volatiles during dry-cured pork coppa processing were characterized.The results showed that 5 kinds of free amino acids,Glu,Lys,Val,Ala,and Leu,were identified as significant contributors to taste.Meanwhile,key volatiles,such as hexanal,nonanal,octanal,benzaldehyde,3-methyl butanoic acid,2-methyl propanoic acid,and ethyl octanoate,greatly contributed to the flavor characteristics of dry-cured pork coppa.Further partial correlation analysis was performed to better elucidate the relationship among parameters.The results revealed that close relationship between endogenous proteases and key substances.RAP not only significantly affected the accumulation of key active-amino acids,but also affected the accumulation of ethyl octanoate,2,3-pentanedione,and 2,3-octanedione by regulating the accumulation of octanoic acid and Leu.In addition,cathepsin B and D,DPP II,DPP IV and RAP notably affected accumulation of hexanal.展开更多
An enduring debate in research revolves around the association between elevated endogenous testosterone levels and prostate cancer. This systematic review is intended to assess the present understanding of the role of...An enduring debate in research revolves around the association between elevated endogenous testosterone levels and prostate cancer. This systematic review is intended to assess the present understanding of the role of endogenous testosterone in the diagnosis and treatment of low- and intermediate-risk prostate cancer. Our search strategy was the following: (endogenous testosterone) AND (((low risk) OR (intermediate risk)) AND ((diagnosis) OR (treatment))) AND (prostate cancer);that was applied to PubMed, Web of Science, and Scopus databases to identify pertinent articles. Two investigators performed an independent selection following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The preliminary investigation detected 105 records, and 81 records remained after eliminating duplicates. Following the review of titles and abstracts, 71 articles were excluded. A comprehensive examination of the full text was conducted for 10 articles, excluding 3 of them. After revising the references of eligible articles, other 3 articles were included. We finally identified 10 suitable studies, including three main topics: (1) association between endogenous testosterone and European Association of Urology (EAU) risk classes;(2) association between endogenous testosterone density and the tumor load;and (3) association of endogenous testosterone with tumor upgrading and tumor upstaging. Actual literature about the impact of endogenous testosterone on low- and intermediate-risk prostate cancer is not numerous, but appears to be still conflicting. More investigations are needed to increase the consistency of the literature’s results.展开更多
基金National Natural Science Foundation of China(No.52373281)National Energy-Saving and Low-Carbon Materials Production and Application Demonstration Platform Program,China(No.TC220H06N)。
文摘The research,fabrication and development of piezoelectric nanofibrous materials offer effective solutions to the challenges related to energy consumption and non-renewable resources.However,enhancing their electrical output still remains a significant challenge.Here,a strategy of inducing constrained phase separation on single nanofibers via shear force was proposed.Employing electrospinning technology,a polyacrylonitrile/polyvinylidene difluoride(PAN/PVDF)nanofibrous membrane was fabricated in one step,which enabled simultaneous piezoelectric and triboelectric conversion within a single-layer membrane.Each nanofiber contained independent components of PAN and PVDF and exhibited a rough surface.The abundant frictional contact points formed between these heterogeneous components contributed to an enhanced endogenous triboelectric output,showcasing an excellent synergistic effect of piezoelectric and triboelectric response in the nanofibrous membrane.Additionally,the component mass ratio influenced the microstructure,piezoelectric conformation and piezoelectric performance of the PAN/PVDF nanofibrous membranes.Through comprehensive performance comparison,the optimal mass ratio of PAN to PVDF was determined to be 9∶1.The piezoelectric devices made of the optimal PAN/PVDF nanofibrous membranes with rough nanofiber surfaces generated an output voltage of 20 V,which was about 1.8 times that of the smooth one at the same component mass ratio.The strategy of constrained phase separation on the surface of individual nanofibers provides a new approach to enhance the output performance of single-layer piezoelectric nanofibrous materials.
基金supported in part by the High-tech ship scientific research project of the Ministry of Industry and Information Technology of the People’s Republic of China,and the National Nature Science Foundation of China(Grant No.71671113)the Science and Technology Department of Shaanxi Province(No.2020GY-219)the Ministry of Education Collaborative Project of Production,Learning and Research(No.201901024016).
文摘Ship outfitting is a key process in shipbuilding.Efficient and high-quality ship outfitting is a top priority for modern shipyards.These activities are conducted at different stations of shipyards.The outfitting plan is one of the crucial issues in shipbuilding.In this paper,production scheduling and material ordering with endogenous uncertainty of the outfitting process are investigated.The uncertain factors in outfitting equipment production are usually decision-related,which leads to difficulties in addressing uncertainties in the outfitting production workshops before production is conducted according to plan.This uncertainty is regarded as endogenous uncertainty and can be treated as non-anticipativity constraints in the model.To address this problem,a stochastic two-stage programming model with endogenous uncertainty is established to optimize the outfitting job scheduling and raw material ordering process.A practical case of the shipyard of China Merchants Heavy Industry Co.,Ltd.is used to evaluate the performance of the proposed method.Satisfactory results are achieved at the lowest expected total cost as the complete kit rate of outfitting equipment is improved and emergency replenishment is reduced.
基金supported by the National Natural Science Foundation of China,Nos.82272171(to ZY),82271403(to XL),81941011(to XL),31971279(to ZY),31730030(to XL)the Natural Science Foundation of Beijing,No.7222004(to HD).
文摘The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.
基金supported by the Christiane and Claudia Hempel Foundation for Regenerative Medicineby the James and Elisabeth Cloppenburg, Peek and Cloppenburg Düsseldorf Stiftung(to PK)。
文摘Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
基金supported by the National Natural Science Foundation of China(Nos.22376114 and 22076091)the State Key Joint Laboratory of Environment Simulation and Pollution Control,China(No.21L01ESPC)the Youth Science and Technology Innovation Program of Xiamen Ocean and Fisheries Development Special Funds(No.23YYST062QCB29)。
文摘There are two formation routes of dietary N-nitrosamines:exogenous and endogenous formation.The formation of N-nitrosamines from either source requires precursors with a dialkylamine functional group and a nitrosating agent.Precursors are supplied primarily by amine-rich foods and nitrosating agents are nitrite or its reaction products(N_(2)O_(3) and NO^(+)).Unprocessed fresh foods initially contain zero or only trace amounts of N-nitrosamines while significant amounts of N-nitrosamines can be generated during certain types of food processing.Cooking methods,pH,additives,and storage conditions can affect the formation of N-nitrosamines in foods.We analysed the formation mechanisms/pathways of the three most frequently detected N-nitrosamines in processed meats.Formation of endogenous N-nitrosamines is likely to be greater than that of exogenous N-nitrosamines.Nitrosating agents involved in the formation of endogenous N-nitrosamines are formed from nitrate in vegetables via the nitrate-nitrite-NO cycle.N-nitrosamines are produced in the human stomach and intestine but their formation mechanisms differ.We analysed the mechanism/pathway for the formation of N-nitrosotryptophan from tryptophan in the stomach.The formation of N-nitrosamines in the intestine includes both chemical and microbiological mechanisms.In addition to N-nitrosation,S-nitrosation also occurs in the human body.There is a competitive relationship between the two reactions,and S-nitrosation is more likely to occur in the healthy human body.This paper reviews the mechanisms and factors influencing the formation of exogenous and endogenous dietary N-nitrosamines,which illustrate the importance of microbial-mediated N-nitrosamine formation and the production of endogenous N-nitrosamines.
基金made possible by the National Natural Science Foundation of China (32060422)。
文摘Drought is one of the important stress factors affecting the growth and development processes of wheat in China's arid zones, which severely limits the yield. This study examined the impact of deficit irrigation on the flag leaf protection system and yield of drip-irrigated spring wheat during the growth stages in arid zones. In addition, this study aimed to determine the optimal water supply mode for efficient production under drip irrigation conditions and to provide technical support for water-saving and high-yield cultivation of drip-irrigated wheat. The experiment was conducted with a split plot design using the water-sensitive variety Xinchun 22(XC22) and the drought-tolerant variety Xinchun 6(XC6) as the main plots, while a fully irrigated control(CK, 75–80% FC, where FC is field water holding capacity), mild deficit(T1, 60–65% FC) and moderate deficit(T2, 45–50% FC) at the tillering stage, and mild deficit(J1, 60–65% FC) and moderate deficit(J2, 45–50% FC) at the jointing stage were used as the subplots. Systematic studies were conducted on the regulatory effects of deficit irrigation during the tillering and jointing stages on protective substances, membrane lipid metabolism, endogenous hormones in the flag leaf, and yield of spring wheat. Compared with treatments T2 and J2, treatments T1 and J1 were beneficial for increasing the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT), the levels of proline(Pro), indole-3-acetic acid(IAA), and zeatin riboside(ZR), and the ratios IAA/abscisic acid(ABA), ZR/ABA, IAA/ZR, and(IAA+ZR)/ABA, while reducing the levels of hydrogen peroxide(H2O2), superoxide anion radicals(O2–·), malondialdehyde(MDA), phosphatidic acid(PA), free fatty acids(FFA), ABA, phospholipase D(PLD), and lipoxygenase(LOX), alleviating flag leaf senescence, and increasing yield. Under treatment T1, the SOD, POD, CAT, and Pro levels of flag leaves in XC6 were 11.14, 8.08, 12.98, and 3.66% higher than those of treatment CK, and under treatment J1, they were 6.43, 4.49, 7.36, and 2.50% higher than those of treatment CK. Under treatment T1 in XC6, the IAA, ZR level of the flag leaf, spike number, grains per spike, 1,000-grain weight and yield were 10.50, 5.79, 3.10, 8.84, 3.78, and 10.52% higher than those of treatment CK, and under treatment J1, they were 5.36, 3.94, 2.40, 3.72, 1.37, and 4.46% higher than those of treatment CK. Compared with XC22, XC6 was more conducive to the improvement of flag leaf protective substances, IAA, ZR, dry matter weight, yield components and yield. The correlation analysis showed significant positive correlations between IAA and ZR with SOD, POD, CAT, proline, and yield. IAA and ZR promoted the enhancement of protective enzyme activities, thereby clearing reactive oxygen species to cope with the oxidative stress caused by drought and achieve the effect of delaying senescence. Principal component analysis showed that yield components and dry matter weight, had direct effects on yield. Mild deficiency during the tillering stage without water stress in other stages could effectively optimize yield components, not only achieving high yield while increasing protective substances, but also reducing the reactive oxygen species content. This strategy can be recommended as a water-saving and high-yield production mode for drip irrigation of spring wheat in Xinjiang, China.
基金This retrospective analysis incorporated data from two clinical trials(CTR20220854 and CTR20222843)sponsored by Chongqing Chenan Biopharmaceutical Co.,Ltd.and Jiangsu Hengrui Pharmaceuticals Co.,Ltd.However,these sponsors did not partake in the study design,data interpretation,or manuscript preparation.
文摘BACKGROUND Insulin therapy plays a crucial role in managing diabetes.Regulatory guidelines mandate assessing the pharmacokinetics(PK)and pharmacodynamics(PD)of new insulin formulations with euglycemic clamp techniques before entry into the market.Typically,blood glucose(BG)levels are maintained at 5%below baseline to suppress endogenous insulin secretion in healthy volunteers.However,in scenarios where BG baseline is relatively low,maintaining it at 5%below baseline can increase hypoglycemic risk.Consequently,we adjusted to maintain it at 2.5%below a baseline of<4.00 mmol/L.It remains uncertain whether this adjustment impacts endogenous insulin inhibition or the PD of study insulin.AIM To evaluate and compare the PD and C-peptide status using two different target BG setting methods.METHODS Data came from euglycemic clamp trials assessing the PK/PD of insulin aspart(IAsp)in healthy participants.Target BG was set at 2.5%below baseline for those with a basal BG of<4.00 mmol/L(group A),and at 5%below baseline for others(group B).The area under the curve(AUC)of IAsp(AUC_(IAsp,0-8 h))and GIR from 0 to 8 hours(AUCGIR,0-8 h)was used to characterize the PK and PD of IAsp,respectively.The C-peptide reduction and PK/PD of IAsp were compared between the two groups.RESULTS Out of 135 subjects,15 were assigned to group A and 120 to group B;however,group B exhibited higher basal Cpeptide(1.59±0.36 vs 1.32±0.42 ng/mL,P=0.006).Following propensity score matching to adjust for basal Cpeptide differences,71 subjects(15 in group A and 56 in group B)were analyzed.No significant differences were observed in demographics,IAsp dosage,or clamp quality.Group B showed significantly higher baseline(4.35±0.21 vs 3.91±0.09 mmol/L,P<0.001),target(4.13±0.20 vs 3.81±0.08 mmol/L,P<0.001),and clamped(4.10±0.17 vs 3.80±0.06 mmol/L,P<0.001)BG levels.Both groups exhibited comparable C-peptide suppression(32.5%±10.0%vs 35.6%±12.1%,P=0.370)and similar IAsp activity(AUCGIR,0-8 h:1433±400 vs 1440±397 mg/kg,P=0.952)under nearly equivalent IAsp exposure(AUC_(IAsp,0-8 h):566±51 vs 571±85 ng/mL×h,P=0.840).CONCLUSION Maintaining BG at 2.5%below a baseline of<4.00 mmol/L did not compromise the endogenous insulin suppression nor alter the observed pharmacodynamic effects of the study insulin.
基金supported by the National Key Research and Development Program of China,No.2018YFA0108602the CAMS Initiative for Innovative Medicine,No.2021-1-I2M-019National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-C-042(all to XB)。
文摘Ischemic stroke is a significant global health crisis,frequently resulting in disability or death,with limited therapeutic interventions available.Although various intrinsic reparative processes are initiated within the ischemic brain,these mechanisms are often insufficient to restore neuronal functionality.This has led to intensive investigation into the use of exogenous stem cells as a potential therapeutic option.This comprehensive review outlines the ontogeny and mechanisms of activation of endogenous neural stem cells within the adult brain following ischemic events,with focus on the impact of stem cell-based therapies on neural stem cells.Exogenous stem cells have been shown to enhance the proliferation of endogenous neural stem cells via direct cell-tocell contact and through the secretion of growth factors and exosomes.Additionally,implanted stem cells may recruit host stem cells from their niches to the infarct area by establishing so-called“biobridges.”Furthermore,xenogeneic and allogeneic stem cells can modify the microenvironment of the infarcted brain tissue through immunomodulatory and angiogenic effects,thereby supporting endogenous neuroregeneration.Given the convergence of regulatory pathways between exogenous and endogenous stem cells and the necessity for a supportive microenvironment,we discuss three strategies to simultaneously enhance the therapeutic efficacy of both cell types.These approaches include:(1)co-administration of various growth factors and pharmacological agents alongside stem cell transplantation to reduce stem cell apoptosis;(2)synergistic administration of stem cells and their exosomes to amplify paracrine effects;and(3)integration of stem cells within hydrogels,which provide a protective scaffold for the implanted cells while facilitating the regeneration of neural tissue and the reconstitution of neural circuits.This comprehensive review highlights the interactions and shared regulatory mechanisms between endogenous neural stem cells and exogenously implanted stem cells and may offer new insights for improving the efficacy of stem cell-based therapies in the treatment of ischemic stroke.
基金Supported by National Natural Science Foundation of China(31270674)Science and Technology Planning Project of Zhaoqing City,Guangdong Province(2019N012)National Undergraduate Innovation and Entrepreneurship Training Program(202210580007).
文摘[Objectives]This study was conducted to investigate the regulatory effects of selenium(Se)on the content and balance of endogenous hormones and the function of antioxidant system during seed development in Red sandalwood(Pterocarpus santalinus).[Methods]Two basic treatments,seven single-fertilization treatments,and four combined fertilization treatments were designed.Sampling was conducted at 2,5,8,and 18 weeks after flower withering to measure the embryo abortion percentage(EAP),the contents of three endogenous hormones(IAA,GA_(3),ABA),and the activities of four antioxidant enzymes(CAT,APX,SOD,GR).[Results]Se application significantly inhibited embryo abortion in Red sandalwood,with Na_(2)SeO_(3)[Se(IV)]showing superior effects to Na_(2)SeO_(3)(Se(VI))and far exceeding the efficacy of individual applications of KCl,H_(3)BO_(3),CO(NH_(2))_(2),Ca(H_(2)PO_(4))_(2),NPK compound fertilizer,or EFOF.The combined treatment of Se with NPK compound fertilizer and EFOF[EFOF+NPK compound fertilizer+Se(IV)]was the most effective,reducing the abortion percentage by 77.8%compared with UMC at 18 weeks after flower withering.Se application significantly increased the levels of three endogenous hormones and the(IAA+GA_(3))/ABA ratio in Red sandalwood seeds(including the embryonic stage).In the optimal treatment,the(IAA+GA_(3))content was 240.7%,256.4%,353.7%,and 502.9%higher than that of UMC at 2,5,8,and 18 weeks after flower withering,respectively.Se application also concurrently enhanced antioxidant enzyme activities,with all four antioxidant enzymes in seeds of Se-treated plants showing significant increases.Notably,the selenoenzyme GR maintained considerably high activity even at 18 weeks after flower withering.The EAP was highly significantly negatively correlated with IAA content and GR activity,identifying IAA and(IAA+GA_(3))content as key hormonal indicators and GR as the core antioxidant enzyme,together constituting the central regulatory factors.The results indicate that Se suppresses embryo abortion in Red sandalwood through a dual regulatory pathway:by elevating IAA and GA_(3)levels along with the(IAA+GA_(3))/ABA ratio to optimize hormonal signaling networks,and by enhancing the activities of antioxidant enzymes such as GR to alleviate oxidative stress induced by cool-season low temperatures.[Conclusions]This study provides a theoretical basis and technical strategy for precision fertilization and stress resistance management in the cultivation of Red sandalwood.
文摘AIM:To report the demographic and systemic characteristics of patients,clinical progression of endophthalmitis,and the efficacy of various treatment strategies,with a focus on identifying key factors for preserving vision in eyes with endogenous endophthalmitis due to Klebsiella pneumoniae(K.pneumoniae)liver abscess.METHODS:In this single-center,retrospective case series of 18 patients with endogenous endophthalmitis due to K.pneumoniae liver abscess were analyzed.Ophthalmologic features of endophthalmitis at early,intermediate and advanced stages were obtained from eyes with endophthalmitis of different severities.Prompt vitrectomy was considered primarily for all eyes except for very early endophthalmitis.Intravitreal injections of antibiotics were performed in eyes with endophthalmitis in the very early stages and in eyes where vitrectomy was not available,and additional control of infection was needed after vitrectomy.Evisceration was performed in eyes with corneoscleral perforation,advanced endophthalmitis,perforation with preseptal or orbital cellulitis,uncontrolled infection,or severe pain with no vision.RESULTS:Mean(±standard deviation)age of the 18 patients with endophthalmitis was 64.5±12.2(range:32-84)y,and 14 patients(77.8%)were males.Endophthalmitis tended to involve the retinal parenchyma first and then progressed into the vitreous cavity and anterior segments.However,it presented a tendency to cause massive subretinal abscesses even after vitrectomy with silicone oil tamponade.Very high intraocular pressure with new vessels on the iris(41.7%)were also commonly observed.Although all but three patients had systemic disease such as diabetes or hypertension,visual prognosis after treatment did not appear to depend significantly on underlying comorbidities.A final best-corrected visual acuity better than 20/60 was achieved only when lesions were detected very early,with relatively good initial visual acuity,likely reflecting lower bacterial inoculation in the eye.CONCLUSION:Detection of early endophthalmitis lesions appears to be the only way to preserve good vision in patients with K.pneumoniae liver abscesses.Therefore,proper guidelines for ophthalmologic screening remain to be established for subjects at a high risk of endophthalmitis.
基金supported by the Shandong Provincial Natural Science Foundation(ZR2022QH144).
文摘The phenomenon of fear memory generalization can be defined as the expansion of an individual's originally specific fear responses to a similar yet genuinely harmless stimulus or situation subsequent to the occurrence of a traumatic event[1].Fear generalization within the normal range represents an adaptive evolutionary mechanism to facilitate prompt reactions to potential threats and to enhance the likelihood of survival.
基金supported by the National Natural Science Foundation of China(No.22073090,No.21991132,No.52021002)the National Key R&D Program of China(No.2020YFA0710700)the Funds of Youth Innovation Promotion Association,and the Fundamental Research Funds for the Central Universities(WK3450000009).
文摘CRISPR-based tran-scription regulators(CRISPR-TRs)have revolutionized the field of synthetic biol-ogy by enabling tar-geted activation or repression of any de-sired gene.However,the majority of exist-ing inducible CRISPR-TRs are limited by their dependence on specific sequences,which restricts their flex-ibility and controllability in genetic engineering applications.In this study,we proposed a novel strategy to construct sequence-independent inducible CRISPR-TRs,which is achieved by the design of stem loop 2 in the single guide RNA(sgRNA).Under this strategy,by utiliz-ing toehold-mediated strand displacement(TMSD)reactions between small endogenous molecules(miR-20a and TK1 mRNA)and bridge RNA(bRNA)to link bRNA with sgRNA,we achieved synergistic transcriptional activation of VP64 and p65-HSF1 in response to en-dogenous molecules.To enable response to exogenous molecules,we added response se-quences and bRNA sequences to the 5'end of sgRNA to block sgRNA activity,and achieved activation of sgRNA by shearing the response sequence,called sequential unlimited interlock-ing(SUI).Compared with conventional sequence-restricted interlocking(spacer-blocking hairpin(SBH)),the transcriptional activation ratio between response and non-response to the Cas6A protein using our approach was increased by 2.28-fold.Our work presents a modular and versatile framework for endogenous and exogenous molecule-responsive CRISPR-TRs in mammalian cells,without limitations imposed by sequence dependence.
文摘This paper provides a systematic review of Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging(MALDI-MSI),encompassing its technical principles,experimental workflows,matrix optimization strategies,and recent advancements in plant science applications.It highlights the method's groundbreaking applications in spatial mapping of plant metabolites,dynamic hormone monitoring,and functional studies of tissue microdomains,while offering critical insights into current technical limitations and future research directions.
基金supported by the National Natural Science Foundation of China(No.82272321)the Stanley Foundation from the Stanley Medical Research Institute(SMRI),United States(No.06R-1366)。
文摘The human endogenous retrovirus type W envelope glycoprotein(ERVWE1),located at chromosome 7q21–22,has been implicated in the pathophysiology of schizophrenia.Our previous studies have shown elevated ERVWE1 expression in schizophrenia patients.Growing evidence suggests that autophagy dysfunction contributes to schizophrenia,yet the relationship between ERVWE1 and autophagy remains unclear.In this study,bioinformatics analysis of the human prefrontal cortex RNA microarray dataset(GSE53987)revealed that differentially expressed genes were predominantly enriched in autophagy-related pathways.Clinical data further demonstrated that serum levels of microtubuleassociated protein 1 light chain 3β(LC3B),a key marker of macroautophagy,were significantly elevated in schizophrenia patients compared to controls,and positively correlated with ERVWE1 expression.Cellular and molecular experiments suggested that ERVWE1 promoted macroautophagy by increasing the LC3B II/I ratio,enhancing autophagosome formation,and reducing sequestosome 1(SQSTM1)expression via upregulation of NADPH oxidase activator 1(NOXA1).Concurrently,NOXA1 downregulated the expression of key micromitophagy-related genes,including PTEN-induced kinase 1(PINK1),Parkin RBR E3 ubiquitin-protein ligase(Parkin),and the pyruvate dehydrogenase E1 subunitα1(PDHA1).As a result,ERVWE1,via NOXA1,inhibited micromitophagy by suppressing the expression of PINK1,Parkin,and PDHA1,thereby leading to impaired production of mitochondrialderived vesicles(MDVs).Mechanistically,ERVWE1 enhanced NOXA1 transcription by upregulating upstream transcription factor 2(USF2).In conclusion,ERVWE1 promotes macroautophagy and inhibits micromitophagy through USF2-NOXA1 axis,providing novel mechanistic insight into the role autophagy dysregulation in schizophrenia.These findings suggest that targeting autophagy pathways may offer novel therapeutic strategies for schizophrenia treatment.
文摘BACKGROUND As a non-coding RNA molecule,circular RNAs(circRNAs)have significant specificity,and existing data suggest a close relationship between them and the prognosis of patients with gastric cancer(GC).However,this mechanism has no evidence yet.This article explores the functions of hsa_circRNA_102415 in the malignant behavior and potential downstream signaling of GC cells.The chosen approach is loss of signal and functional gain.AIM To investigate and analyze the relationship between hsa_circRNA_102415 and GC and explore its specific role.Results provide reference for other researchers to develop targeted treatment plans.METHODS The gene expression omnibus(GEO)database can be used to obtain the microarray dataset GSE83521.Data were analyzed using the GEO2R tool to identify differences in circRNAs between normal and GC samples.Quantitative real-time polymerase chain reaction was used to detect differentially expressed genes in GC tissue samples and adjacent cancer tissue samples.GC cells were transfected with small interfering-hsa_circRNA_104415 and plasmid DNA(pcDNA)-hsa_ircRNA_102415.Multiple detection methods,such as Transwell and cell counting kit 8,were used to evaluate cellular physiological activities,including cell invasion and proliferation.The relationship between Wnt family members 2B,microRNA(miR)-4529-5p,etc.,including argonaute 2-RNA immunoprecipitation and luciferase reporter genes was analyzed.Rescue experiments were conducted to analyze and explore the relationship between the malignant behavior of GC cells and hsa_circRNA_102415.RESULTS GEO2R analysis confirmed that hsa_circRNA_102415 had significantly higher expression levels in disease tissues.hsa_circRNA_102415 and miR-4529-5p showed a negative correlation in disease cells,suggesting that hsa_circRNA_102415 upregulated WNT2B expression in GC cells as a competing endogenous RNA for miR-4529-5p.miR-4529-5p mimic or small interfering-WNT2B reversed the effects of pcDNA-hsa_circRNA_102415 or miR-4529-5p inhibitor on cell malignant functions.CONCLUSION miR-4529-5p was used to successfully activate the potential of WNT2B,clarify the role of hsa_circRNA_102415 in GC cells,and provide reference for other researchers to develop targeted treatment plans.
基金supported by the National Natural Science Foundation of China(Nos.22222610,22376202,and 22193051)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB0750100)+1 种基金Chinese Academy of Sciences Project for Young in Basic Research(No.YSBR-086)the National Key R&D Program of China(Nos.2023YFF0614200 and 2023YFC3708301)。
文摘Accurately distinguishing between the endogenous formation and exogenous exposure of Fe-bearing particles(e.g.,magnetic Fe particles)within biological organisms is the prerequisite for scientifically evaluating their health risks.However,this remains a challenging task due to lacking the comprehensive understanding of the endogenous formation process of Fe-bearing particles.Here,we report the formation dynamics of Fe-bearing particles under conditions closely resembling actual physiological conditions,and compare the morphological and structural differences between endogenous and exogenous Fe-bearing particles.We find that Fe-bearing particles can indeed form under physiological conditions at 37℃.In this process,phosphate plays a crucial role in the oxidation and mineralization of iron ions.Moreover,endogenously formed Fe-bearing particles typically have a diameter of less than8 nm,and iron is the only metal element present.Therefore,we propose that Fe-bearing particles found in the body with a diameter larger than 8 nm are mainly derived from exogenous exposure.For Fe-bearing particles smaller than 8 nm,it is necessary to combine associated elements and crystal structure characteristics to distinguish between endogenous and exogenous sources.This study provides direct evidence from endogenous metabolism for tracing Fe-bearing particles,especially magnetic iron particles,within the human body.
基金supported by the National Natural Science Foundation of China,Nos. 82173806 and U1803281Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science,Nos. 2021-I2M-1-030 and 2022-I2M-2-002Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences,No. 2022-JKCS-08 (all to RL)。
文摘Long noncoding RNA and microRNA are regulatory noncoding RNAs that are implicated in Alzheimer's disease, but the role of long noncoding RNA-associated competitive endogenous RNA has not been fully elucidated. The long noncoding RNA growth arrest-specific 5(GAS5) is a member of the 5′-terminal oligopyrimidine gene family that may be involved in neurological disorders, but its role in Alzheimer's disease remains unclear. This study aimed to investigate the function of GAS5 and construct a GAS5-associated competitive endogenous RNA network comprising potential targets. RNA sequencing results showed that GAS5 was upregulated in five familial Alzheimer's disease(5×FAD) mice, APPswe/PSEN1dE9(APP/PS1) mice, Alzheimer's disease-related APPswe cells, and serum from patients with Alzheimer's disease. Functional experiments with targeted overexpression and silencing demonstrated that GAS5 played a role in cognitive dysfunction and multiple Alzheimer's disease-associated pathologies, including tau hyperphosphorylation, amyloid-beta accumulation, and neuronal apoptosis. Mechanistic studies indicated that GAS5 acted as an endogenous sponge by competing for microRNA-23b-3p(miR-23b-3p) binding to regulate its targets glycogen synthase kinase 3beta(GSK-3β) and phosphatase and tensin homologue deleted on chromosome 10(PTEN) expression in an Argonaute 2-induced RNA silencing complex(RISC)-dependent manner. GAS5 inhibited miR-23b-3p-mediated GSK-3β and PTEN cascades with a feedforward PTEN/protein kinase B(Akt)/GSK-3β linkage. Furthermore, recovery of GAS5/miR-23b-3p/GSK-3β/PTEN pathways relieved Alzheimer's disease-like symptoms in vivo, indicated by the amelioration of spatial cognition, neuronal degeneration, amyloid-beta load, and tau phosphorylation. Together, these findings suggest that GAS5 promotes Alzheimer's disease pathogenesis. This study establishes the functional convergence of the GAS5/miR-23b-3p/GSK-3β/PTEN pathway on multiple pathologies, suggesting a candidate therapeutic target in Alzheimer's disease.
基金supported by the National Natural Science Foundation of China,Nos.81941011(to XL),31771053(to HD),31730030(to XL),31971279(to ZY),31900749(to PH),31650001(to XL),31320103903(to XL),31670988(to ZY)the Natural Science Foundation of Beijing,Nos.7222004(to HD)+1 种基金a grant from Ministry of Science and Technology of China,Nos.2017YFC1104002(to ZY),2017YFC1104001(to XL)a grant from Beihang University,No.JKF-YG-22-B001(to FH)。
文摘Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.
基金financially supported by the National Natural Science Foundation of China(32001728,32172248)the Taishan Industrial Experts Program+1 种基金the Guizhou High-level Innovative Talent Training Project(Qianke Cooperation Platform Talent number[2016]5662)Guizhou Science and Technology Innovation Talent Team of Ecological Characteristic Meat Products.(QKHPTRC[2020]5004)。
文摘Dry-cured meat products are considerably popular around the world due to unique flavor.Proteolysis is one of the enzymatic reactions from which flavor substances are derived,which is affected by endogenous proteases.The purpose aimed to reveal the potential relationship between endogenous proteases and key flavor substances in dry-cured pork coppa in this paper.The dynamic changes of endogenous proteases activity,free amino acids,and volatiles during dry-cured pork coppa processing were characterized.The results showed that 5 kinds of free amino acids,Glu,Lys,Val,Ala,and Leu,were identified as significant contributors to taste.Meanwhile,key volatiles,such as hexanal,nonanal,octanal,benzaldehyde,3-methyl butanoic acid,2-methyl propanoic acid,and ethyl octanoate,greatly contributed to the flavor characteristics of dry-cured pork coppa.Further partial correlation analysis was performed to better elucidate the relationship among parameters.The results revealed that close relationship between endogenous proteases and key substances.RAP not only significantly affected the accumulation of key active-amino acids,but also affected the accumulation of ethyl octanoate,2,3-pentanedione,and 2,3-octanedione by regulating the accumulation of octanoic acid and Leu.In addition,cathepsin B and D,DPP II,DPP IV and RAP notably affected accumulation of hexanal.
文摘An enduring debate in research revolves around the association between elevated endogenous testosterone levels and prostate cancer. This systematic review is intended to assess the present understanding of the role of endogenous testosterone in the diagnosis and treatment of low- and intermediate-risk prostate cancer. Our search strategy was the following: (endogenous testosterone) AND (((low risk) OR (intermediate risk)) AND ((diagnosis) OR (treatment))) AND (prostate cancer);that was applied to PubMed, Web of Science, and Scopus databases to identify pertinent articles. Two investigators performed an independent selection following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The preliminary investigation detected 105 records, and 81 records remained after eliminating duplicates. Following the review of titles and abstracts, 71 articles were excluded. A comprehensive examination of the full text was conducted for 10 articles, excluding 3 of them. After revising the references of eligible articles, other 3 articles were included. We finally identified 10 suitable studies, including three main topics: (1) association between endogenous testosterone and European Association of Urology (EAU) risk classes;(2) association between endogenous testosterone density and the tumor load;and (3) association of endogenous testosterone with tumor upgrading and tumor upstaging. Actual literature about the impact of endogenous testosterone on low- and intermediate-risk prostate cancer is not numerous, but appears to be still conflicting. More investigations are needed to increase the consistency of the literature’s results.
