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
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.
We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury.While exosomes are recognized as playing a pivotal role in neural stem cells exocrine func...We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury.While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains unclear.To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury.Subsequently,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted exosomes.The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes.Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control group.Construction of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury.TSC2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury zone.Furthermore,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells.Further assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways.In addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways.Collectively,these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.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
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
Phosphorus(P)is the main limiting factor in eutrophication.Sediment P can be released decades after its accumulation.Lake restoration requires the reduction of internal sediment P loading.Although we tried to provide ...Phosphorus(P)is the main limiting factor in eutrophication.Sediment P can be released decades after its accumulation.Lake restoration requires the reduction of internal sediment P loading.Although we tried to provide a comprehensive summary of the state-of-the-art sediment P control technologies,our analyses in this review are focused on the mechanisms,control effects,and application conditions of different in-situ technologies including physical control,chemical control,ecological remediation,and combined control technology.The design principles,feasibility,operation parameters,and pros&cons of these technologies are analyzed and compared.More efforts are needed to improve in-situ sediment P control technologies so as to enhance the interaction between materials and plant communities and promote the adsorption and fixation of active P in sediments.The control materials for internal sediment P loading need to be further studied in terms of their functional properties,pre-evaluation of the P control effect,and engineering applications.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
Ferroptosis is a newly proposed type of programmed cell death,which has been associated with a variety of diseases including tumors.Researchers have thereby presented nanoplatforms to mediate ferroptosis for anti-canc...Ferroptosis is a newly proposed type of programmed cell death,which has been associated with a variety of diseases including tumors.Researchers have thereby presented nanoplatforms to mediate ferroptosis for anti-cancer therapy.However,the development of ferroptosis-based nanotherapeutics is generally hindered by the limited penetration depth in tumors,poor active pharmaceutical ingredient(API)loading content and the systemic toxicity.Herein,self-propelled ferroptosis nanoinducers composed of two endogenous proteins,glucose oxidase and ferritin,are presented to show enhanced tumor inhibition via ferroptosis while maintaining high API and biocompatibility.The accumulation of our proteomotors at tumor regions is facilitated by the active tumor-targeting effect of ferritin.The enhanced diffusion of proteomotors is then actuated by efficiently decomposing glucose into gluconic acid and H_(2)O_(2),leading to deeper penetration and enhanced uptake into tumors.Under the synergistic effect of glucose oxidase and ferritin,the equilibrium between reactive oxygen species and GSH is damaged,leading to lipid peroxidation.As a result,by inducing ferroptosis,our self-propelled ferroptosis nanoinducers exhibit enhanced tumor inhibitory effects.This work paves a way for the construction of a biocompatible anticancer platform with enhanced diffusion utilizing only two endogenous proteins,centered around the concept of ferroptosis.展开更多
The 5G-R network is on the verge of entering the construction stage.Given that the dedicated network for railways is closely linked to train operation safety,there are extremely high requirements for network security....The 5G-R network is on the verge of entering the construction stage.Given that the dedicated network for railways is closely linked to train operation safety,there are extremely high requirements for network security.As a result,there is an urgent need to conduct research on 5G-R network security.To comprehensively enhance the end-to-end security protection of the 5G-R network,this study summarized the security requirements of the GSM-R network,analyzed the security risks and requirements faced by the 5G-R network,and proposed an overall 5G-R network security architecture.The security technical schemes were detailed from various aspects:5G-R infrastructure security,terminal access security,networking security,operation and maintenance security,data security,and network boundary security.Additionally,the study proposed leveraging the 5G-R security situation awareness system to achieve a comprehensive upgrade from basic security technologies to endogenous security capabilities within the 5G-R system.展开更多
Software-Defined Perimeter(SDP)provides a logical perimeter to restrict access to services.However,due to the security vulnerability of a single controller and the programmability lack of a gateway,existing SDP is fac...Software-Defined Perimeter(SDP)provides a logical perimeter to restrict access to services.However,due to the security vulnerability of a single controller and the programmability lack of a gateway,existing SDP is facing challenges.To solve the above problems,we propose a flexible and secure SDP mechanism named Mimic SDP(MSDP).MSDP consists of endogenous secure controllers and a dynamic gateway.The controllers avoid single point failure by heterogeneity and redundancy.And the dynamic gateway realizes flexible forwarding in programmable data plane by changing the processing of packet construction and deconstruction,thereby confusing the potential adversary.Besides,we propose a Markov model to evaluate the security of our SDP framework.We implement a prototype of MSDP and evaluate it in terms of functionality,performance,and scalability in different groups of systems and languages.Evaluation results demonstrate that MSDP can provide a secure connection of 93.38%with a cost of 6.34%under reasonable configuration.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
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
[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
The vaginal microbiome plays a pivotal role in maintaining vaginal health and protecting the host from various diseases.There is a broad agreement within the scientific community that the vaginal microbiome exhibits s...The vaginal microbiome plays a pivotal role in maintaining vaginal health and protecting the host from various diseases.There is a broad agreement within the scientific community that the vaginal microbiome exhibits stable bacterial diversity,influenced by age and gonadal hormone levels,and is classified into distinct Community-State Types.A healthy vaginal microbiome is typically characterized by a predominance of Lactobacillus spp.,which acidifies the vaginal environment and is essential in defending against invading microbial pathogens.This review examines the evolution of the vaginal microbiome’s composition throughout a woman’s life.It also explores how exogenous factors influence the homeostasis of this microbiome,leading to either a state of eubiosis or dysbiosis.The main factors supporting eubiosis of the vaginal microbiome include diet,probiotic intake,certain personal hygiene practices,and hormonal contraceptives,while the major contributors to dysbiosis are psychosocial stress,tobacco smoking,and sexual activity.This state of dysbiosis is strongly associated with a range of adverse vaginal health outcomes,including preterm birth,bacterial vaginosis,pelvic inflammatory disease,and a higher risk of sexually transmitted infections.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
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
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
BACKGROUND Endogenous regeneration of pancreatic isletβ-cells is a path to cure both type 1 and advanced type 2 diabetes.Pancreatic cancer cell line-1(PANC-1),a human pancreatic islet progenitor cell line,can be indu...BACKGROUND Endogenous regeneration of pancreatic isletβ-cells is a path to cure both type 1 and advanced type 2 diabetes.Pancreatic cancer cell line-1(PANC-1),a human pancreatic islet progenitor cell line,can be induced by trypsin to differentiate into insulin-secreting islet-like aggregates(ILAs).However,the underlying mechanism has not been explored.AIM To explore the mechanism and signaling pathway of trypsin-induced differentiation of islet progenitor cells into insulin-secreting cells.METHODS PANC-1 cells were induced by trypsin to form ILAs and differentiate into insulinsecreting cells.Clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9 knockout and small interfering RNA knockdown techniques were used to investigate membrane proteins and downstream signaling pathways involved in the process.RESULTS The extracellular domain of membrane receptor E-cadherin hydrolyzed by trypsin induced the aggregation of PANC-1 cells and stimulated E-cadherin-recruited casein kinase-1γ3,which specifically phosphorylated the Ser655/Thr658 site ofα-catenin in the cadherin-catenin complex,participating in the process of PANC-1 differentiation and affecting the maturation of differentiated ILAs.CONCLUSION The current study reveals the mechanism by which trypsin promotes PANC-1 cell differentiation into islet-like cells,providing a novel approach for endogenous isletβ-cell regeneration.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 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,No.81801907(to NC)Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research,No.ZDSYS20230626091402006(to NC)+2 种基金Sanming Project of Medicine in Shenzhen,No.SZSM201911002(to SL)Foundation of Shenzhen Committee for Science and Technology Innovation,Nos.JCYJ20230807110310021(to NC),JCYJ20230807110259002(to JL)Science and Technology Program of Guangzhou,No.2024A04J4716(to TL)。
文摘We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury.While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains unclear.To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury.Subsequently,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted exosomes.The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes.Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control group.Construction of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury.TSC2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury zone.Furthermore,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells.Further assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways.In addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways.Collectively,these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.
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 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financially supported by the National Natural Science Foundation of China(Nos.32201384,31830013,U20A2010)。
文摘Phosphorus(P)is the main limiting factor in eutrophication.Sediment P can be released decades after its accumulation.Lake restoration requires the reduction of internal sediment P loading.Although we tried to provide a comprehensive summary of the state-of-the-art sediment P control technologies,our analyses in this review are focused on the mechanisms,control effects,and application conditions of different in-situ technologies including physical control,chemical control,ecological remediation,and combined control technology.The design principles,feasibility,operation parameters,and pros&cons of these technologies are analyzed and compared.More efforts are needed to improve in-situ sediment P control technologies so as to enhance the interaction between materials and plant communities and promote the adsorption and fixation of active P in sediments.The control materials for internal sediment P loading need to be further studied in terms of their functional properties,pre-evaluation of the P control effect,and engineering applications.
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 National Key Research and Development Program of China(No.2022YFA1206900)National Natural Science Foundation of China(Nos.22175083,82204415,51973241,22375224)GuangDong Basic and Applied Basic Research Foundation(No.2021A1515220187)。
文摘Ferroptosis is a newly proposed type of programmed cell death,which has been associated with a variety of diseases including tumors.Researchers have thereby presented nanoplatforms to mediate ferroptosis for anti-cancer therapy.However,the development of ferroptosis-based nanotherapeutics is generally hindered by the limited penetration depth in tumors,poor active pharmaceutical ingredient(API)loading content and the systemic toxicity.Herein,self-propelled ferroptosis nanoinducers composed of two endogenous proteins,glucose oxidase and ferritin,are presented to show enhanced tumor inhibition via ferroptosis while maintaining high API and biocompatibility.The accumulation of our proteomotors at tumor regions is facilitated by the active tumor-targeting effect of ferritin.The enhanced diffusion of proteomotors is then actuated by efficiently decomposing glucose into gluconic acid and H_(2)O_(2),leading to deeper penetration and enhanced uptake into tumors.Under the synergistic effect of glucose oxidase and ferritin,the equilibrium between reactive oxygen species and GSH is damaged,leading to lipid peroxidation.As a result,by inducing ferroptosis,our self-propelled ferroptosis nanoinducers exhibit enhanced tumor inhibitory effects.This work paves a way for the construction of a biocompatible anticancer platform with enhanced diffusion utilizing only two endogenous proteins,centered around the concept of ferroptosis.
文摘The 5G-R network is on the verge of entering the construction stage.Given that the dedicated network for railways is closely linked to train operation safety,there are extremely high requirements for network security.As a result,there is an urgent need to conduct research on 5G-R network security.To comprehensively enhance the end-to-end security protection of the 5G-R network,this study summarized the security requirements of the GSM-R network,analyzed the security risks and requirements faced by the 5G-R network,and proposed an overall 5G-R network security architecture.The security technical schemes were detailed from various aspects:5G-R infrastructure security,terminal access security,networking security,operation and maintenance security,data security,and network boundary security.Additionally,the study proposed leveraging the 5G-R security situation awareness system to achieve a comprehensive upgrade from basic security technologies to endogenous security capabilities within the 5G-R system.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFB2901304)。
文摘Software-Defined Perimeter(SDP)provides a logical perimeter to restrict access to services.However,due to the security vulnerability of a single controller and the programmability lack of a gateway,existing SDP is facing challenges.To solve the above problems,we propose a flexible and secure SDP mechanism named Mimic SDP(MSDP).MSDP consists of endogenous secure controllers and a dynamic gateway.The controllers avoid single point failure by heterogeneity and redundancy.And the dynamic gateway realizes flexible forwarding in programmable data plane by changing the processing of packet construction and deconstruction,thereby confusing the potential adversary.Besides,we propose a Markov model to evaluate the security of our SDP framework.We implement a prototype of MSDP and evaluate it in terms of functionality,performance,and scalability in different groups of systems and languages.Evaluation results demonstrate that MSDP can provide a secure connection of 93.38%with a cost of 6.34%under reasonable configuration.
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 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.
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The vaginal microbiome plays a pivotal role in maintaining vaginal health and protecting the host from various diseases.There is a broad agreement within the scientific community that the vaginal microbiome exhibits stable bacterial diversity,influenced by age and gonadal hormone levels,and is classified into distinct Community-State Types.A healthy vaginal microbiome is typically characterized by a predominance of Lactobacillus spp.,which acidifies the vaginal environment and is essential in defending against invading microbial pathogens.This review examines the evolution of the vaginal microbiome’s composition throughout a woman’s life.It also explores how exogenous factors influence the homeostasis of this microbiome,leading to either a state of eubiosis or dysbiosis.The main factors supporting eubiosis of the vaginal microbiome include diet,probiotic intake,certain personal hygiene practices,and hormonal contraceptives,while the major contributors to dysbiosis are psychosocial stress,tobacco smoking,and sexual activity.This state of dysbiosis is strongly associated with a range of adverse vaginal health outcomes,including preterm birth,bacterial vaginosis,pelvic inflammatory disease,and a higher risk of sexually transmitted infections.
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 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.
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.82073908.
文摘BACKGROUND Endogenous regeneration of pancreatic isletβ-cells is a path to cure both type 1 and advanced type 2 diabetes.Pancreatic cancer cell line-1(PANC-1),a human pancreatic islet progenitor cell line,can be induced by trypsin to differentiate into insulin-secreting islet-like aggregates(ILAs).However,the underlying mechanism has not been explored.AIM To explore the mechanism and signaling pathway of trypsin-induced differentiation of islet progenitor cells into insulin-secreting cells.METHODS PANC-1 cells were induced by trypsin to form ILAs and differentiate into insulinsecreting cells.Clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9 knockout and small interfering RNA knockdown techniques were used to investigate membrane proteins and downstream signaling pathways involved in the process.RESULTS The extracellular domain of membrane receptor E-cadherin hydrolyzed by trypsin induced the aggregation of PANC-1 cells and stimulated E-cadherin-recruited casein kinase-1γ3,which specifically phosphorylated the Ser655/Thr658 site ofα-catenin in the cadherin-catenin complex,participating in the process of PANC-1 differentiation and affecting the maturation of differentiated ILAs.CONCLUSION The current study reveals the mechanism by which trypsin promotes PANC-1 cell differentiation into islet-like cells,providing a novel approach for endogenous isletβ-cell regeneration.
