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
Background:Diquat,a commonly employed bipyridyl herbicide,is recognized for its hepatotoxic effects attributed to the generation of reactive oxygen species.Baicalin(BAI),a flavonoid derivative,has garnered significant...Background:Diquat,a commonly employed bipyridyl herbicide,is recognized for its hepatotoxic effects attributed to the generation of reactive oxygen species.Baicalin(BAI),a flavonoid derivative,has garnered significant research interest for its hepatoprotective properties.Nevertheless,the clinical application of BAI is constrained by its limited water solubility and poor bioavailability.To address these challenges,BAI-nanoliposome(BAI-NL)has emerged as a novel drug delivery platform aimed at enhancing therapeutic outcomes.Methods:We used diquat-induced liver injury mouse model and AML12 hepatocytes to test the pro-tective effect of BAI and BAI-NL on liver inflammation,oxidative stress,and mitochondrial function.The parameters included histological,biochemical,and molecular biological analyses.Results:In the diquat-induced model,both BAI and BAI-NL exhibited effectiveness on attenuating liver inflammation.Ex vivo analyses further indicated that BAI-NL was superior to BAI in preserving mito-chondrial membrane potential,reducing oxidative stress,and modulating the phosphatase and tensin homolog-induced putative kinase 1(PINK1)/Parkin RBR E3 ubiquitin-protein ligase(Parkin)signaling pathway.These findings enhanced mitophagy and facilitated the removal of damaged mitochondria.Conclusions:BAI-NL exhibited superior hepatoprotective effects compared to free BAI,possibly by re-ducing inflammation,preserving mitochondrial homeostasis,and reinstating autophagic balance through modulation of the PINK1/Parkin signaling pathway.These outcomes indicate a groundbreaking method for addressing liver diseases and underscore the potential of nanoliposome technology in augmenting the efficacy of natural compounds.展开更多
Here we reported an effective method to solve the rate-limiting steps, such as the reduction of Fe^(3+) to Fe^(2+) and an invalid decomposition of H2O2 in a conventional Fenton-like reaction. A magnetic heterogeneous ...Here we reported an effective method to solve the rate-limiting steps, such as the reduction of Fe^(3+) to Fe^(2+) and an invalid decomposition of H2O2 in a conventional Fenton-like reaction. A magnetic heterogeneous photocatalyst, Fe3O4-schwertmannite(Fe3O4-sch) was successfully developed by adding Fe3O4 in the formation process of schwertmannite. Fe3O4-sch shows excellent electrons transfer ability and high utilization efficiency of H2O2(98.5%). The catalytic activity of Fe3O4-sch was studied through the degradation of phenol in the heterogeneous photo-Fenton process. Phenol degradation at a wide pH(3-9) was up to 98% within 6 min under visible light illumination with the Fe3O4-sch as heterogeneous Fenton catalyst, which was higher than that using pure schwertmannite or Fe3O4. The excellent photocatalytic performance of Fe3O4-sch is ascribed to the effective recycling between ≡Fe^(3+) and ≡Fe^(2+) by the photo-generated electron, and also profit from the formation of the "Z-Scheme" system. According to the relevant data, photocatalytic mechanism of Fe3O4-sch for degrading phenol was proposed. This study not only provides an efficient way of enhancing heterogeneous Fenton reaction, but also gives potential application for iron oxyhydroxysulfate mineral.展开更多
Decreased functional β-cell mass is the hallmark of diabetes, but the cause of this metabolic defect remains elusive. Here, we show that the levels of the growth factor receptor-bound protein 10(GRB10), a negative re...Decreased functional β-cell mass is the hallmark of diabetes, but the cause of this metabolic defect remains elusive. Here, we show that the levels of the growth factor receptor-bound protein 10(GRB10), a negative regulator of insulin and m TORC1 signaling, are markedly induced in islets of diabetic mice and high glucose-treated insulinoma cell line INS-1 cells. β-cell-specific knockout of Grb10 in mice increased β-cell mass and improved β-cell function. Grb10-deficient β-cells exhibit enhanced m TORC1 signaling and reduced β-cell dedifferentiation, which could be blocked by rapamycin. On the contrary, Grb10 overexpression induced β-cell dedifferentiation in MIN6 cells. Our study identifies GRB10 as a critical regulator of β-cell dedifferentiation and β-cell mass, which exerts its effect by inhibiting m TORC1 signaling.展开更多
Objective Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs;however,concerns regarding complexities and side effects persist,driving research for more ...Objective Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs;however,concerns regarding complexities and side effects persist,driving research for more effective,low-risk strategies.The promotion of white adipose tissue(WAT)browning has emerged as a promising approach.Moreover,alisol B 23-acetate(AB23A)has demonstrated efficacy in addressing metabolic disorders,suggesting its potential as a therapeutic agent in obesity management.Therefore,in this study,we aimed to investigate the therapeutic potential of AB23A for mitigating obesity by regulating metabolic phenotypes and lipid distribution in mice fed a high-fat diet(HFD).Methods An obesity mouse model was established by administration of an HFD.Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests.Adipocyte size was determined using hematoxylin and eosin staining.The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction.Metabolic cage monitoring involved the assessment of various parameters,including food and water intake,energy metabolism,respiratory exchange rates,and physical activity.Moreover,oil red O staining was used to evaluate intracellular lipid accumulation.A bioinformatic analysis tool for identifying the molecular mechanisms of traditional Chinese medicine was used to examine AB23A targets and associated signaling pathways.Results AB23A administration significantly reduced the weight of obese mice,decreased the mass of inguinal WAT,epididymal WAT,and perirenal adipose tissue,improved glucose and insulin metabolism,and reduced adipocyte size.Moreover,treatment with AB23A promoted the expression of browning markers in WAT,enhanced overall energy metabolism in mice,and had no discernible effect on food intake,water consumption,or physical activity.In 3T3-L1 cells,AB23A inhibited lipid accumulation,and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulatory element-binding protein-1(mTOR-SREBP1)signaling pathway.Furthermore,3-isobutyl-1-methylxanthine,dexamethasone and insulin,at concentrations of 0.25 mmol/L,0.25μmol/L and 1μg/mL,respectively,induced activation of the mTOR-SREBP1 signaling pathway,which was further strengthened by an mTOR activator MHY1485.Notably,MHY1485 reversed the beneficial effects of AB23A in 3T3-L1 cells.Conclusion AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway,offering a potential strategy to prevent obesity.展开更多
One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between...One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors.Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse models.Moreover,there is a direct relationship between pIgR expression and transaminase levels in patients with AIH.In this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH.Reg3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota disruption.Conversely,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis.RNA sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through pIgR.Furthermore,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in AIH.Through this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.展开更多
Objective:To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer patients with indications for breast cancer susceptibility genes 1/2(BRCA1/2)genetic testing in Chin...Objective:To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer patients with indications for breast cancer susceptibility genes 1/2(BRCA1/2)genetic testing in China.Methods:Based on the indication criteria for BRCA genetic testing specified in the National Comprehensive Cancer Network(NCCN)clinical practice guidelines in oncology,genetic/familial high-risk assessment:Breast and ovarian(Version 2.2019),a retrospective analysis was performed on patients with early-stage invasive breast cancer treated at Breast Disease Center,Peking University First Hospital between January 2008 and December 2016.Clinicopathological characteristics of all patients were analyzed,and prognoses were calculated using the KaplanMeier method and a Cox proportionate hazards model.Results:A total of 906 early-stage breast cancer patients who had indications for BRCA genetic testing and had complete clinicopathological data and follow-up information were included in the study group,accounting for34.7%of all breast cancer patients treated in Breast Disease Center,Peking University First Hospital during the study period.Compared with breast cancer patients without indications for BRCA genetic testing,the overall survival(OS)and disease-free survival(DFS)of patients with indications were not significantly different.In the study group,patients with premenopausal status,high T stage,lymph node positive,estrogen receptor(ER)negative,Ki-67>20%and presence of a vascular tumor thrombus had worse prognosis.There were more family histories of gastrointestinal cancer in patients with related indications than in patients without such indications.Conclusions:Single-center data showed that more than 30%of patients with early-stage breast cancer had indications for BRCA genetic testing.There was no prognostic difference in patients with or without indications for BRCA genetic testing.Premenopausal status,high T stage,lymph node positive,ER negative,Ki-67>20%,and presence of a vascular tumor thrombus were associated with poor prognosis.展开更多
The emergence of Event-based Social Network(EBSN) data that contain both social and event information has cleared the way to study the social interactive relationship between the virtual interactions and physical inte...The emergence of Event-based Social Network(EBSN) data that contain both social and event information has cleared the way to study the social interactive relationship between the virtual interactions and physical interactions. In existing studies, it is not really clear which factors affect event similarity between online friends and the influence degree of each factor. In this study, a multi-layer network based on the Plancast service data is constructed. The the user’s events belongingness is shuffled by constructing two null models to detect offline event similarity between online friends. The results indicate that there is a strong correlation between online social proximity and offline event similarity. The micro-scale structures at multi-levels of the Plancast online social network are also maintained by constructing 0 k–3 k null models to study how the micro-scale characteristics of online networks affect the similarity of offline events. It is found that the assortativity pattern is a significant micro-scale characteristic to maintain offline event similarity. Finally, we study how structural diversity of online friends affects the offline event similarity. We find that the subgraph structure of common friends has no positive impact on event similarity while the number of common friends plays a key role, which is different from other studies. In addition, we discuss the randomness of different null models, which can measure the degree of information availability in privacy protection. Our study not only uncovers the factors that affect offline event similarity between friends but also presents a framework for understanding the pattern of human mobility.展开更多
GPCRs are dominant targets for approved drugs and the discovery of lead compound targeting them is still challengeable.Affinity-based screening technique is a promising platform to uncover GPCR ligands.However,the int...GPCRs are dominant targets for approved drugs and the discovery of lead compound targeting them is still challengeable.Affinity-based screening technique is a promising platform to uncover GPCR ligands.However,the intrinsic activities of them are seldom simultaneously determined during the screening.Taking beta2-adrenoceptor(β2AR)as a probe,this work created a strategy for screening GPCR ligands with simultaneous characterization of their downstream G protein binding responses associated with GTP.The strategy included(i)the design and expression of a protein miniature formed byβ2AR and G proteinα-subunit(Gαs)using circularly permuted HaloTag(cpHalo)as a flexible linker;(ii)immobilization of the miniature onto silica gel by a click dehalogenation reaction;(iii)systematic characterization of the immobilized miniature by fluorescent and chromatographic studies,and(iv)simulating of ligand-inducedβ2AR-Gαs signaling cascade by chromatographic assays using GTP as an indicator.The immobilized miniature exhibited specificity toβ2AR and Gαs antibodies and ligands.The specificity is stable at least within fifteen days with the variation less than 1%.The intrinsic activities ofβ2AR ligands were distinguished by the changes of GTP chromatographic behaviors on Gαs-cpHalo-β2AR column.Agonists strengthened the binding affinity and kinetics of GTP with Gαs,while antagonist did not give any effect on them.With the intrinsic activity evaluation,we believe,it will improve the attributes of chromatographic methods for drug discovery efforts with minimizing false-positive results.展开更多
Here,a new designed core/satellite gold nanoprobe was developed for detecting trace mount of benzoyl peroxide(BPO) based on its deboronation.This gold nanoassembly(the BE-Au NPs_(12/65)) wa s constructed via borate es...Here,a new designed core/satellite gold nanoprobe was developed for detecting trace mount of benzoyl peroxide(BPO) based on its deboronation.This gold nanoassembly(the BE-Au NPs_(12/65)) wa s constructed via borate ester formation between large 4-mercaptophenylboronic acid(MPBA) modified Au NPs(the MPBAAu NPs_(65),as cores) and small dopamine modified AuNPs(the D PA-AuNPs_(12),as satellites).Particularly,upon addition of BPO,it would trigger the deboronation for the BE-AuNPs_(12/65) probes accompanying with distinct color changes from blue,purple to wine red,which implied the disassembly of the core/satellite nanostructure after the breakage of carbon to boron chemical bond.By measuring the absorbance ratio at 665 nm and 545 nm,quantification of BPO was achieved in the range of 10.0-100.0 nmol/L,which could also be easily observed by naked eyes.The nanoprobe utilized a boronate deprotection mechanism and the LSPR properties of Au NPs to provide high selectivity for detecting BPO over similar ROS/RNS with the limit of detection as low as 7.2 nmol/L.The practical applicability of this assay was verified through successful determining BPO in flour samples,which demonstrated its great potentials in food safety field.展开更多
A sulfonium ylide participated alkylation and arylation under transition-metal free conditions is described.The disparate reaction pattern allowed the separate activation of non-ylidic S-alkyl and S-aryl bond.Under ac...A sulfonium ylide participated alkylation and arylation under transition-metal free conditions is described.The disparate reaction pattern allowed the separate activation of non-ylidic S-alkyl and S-aryl bond.Under acidic conditions,sulfonium ylides serve as alkyl cation precursors which facilitate the alkylations.While under alkaline conditions,cleavage of non-ylidic S-aryl bond produces O-arylated compounds efficiently.The robustness of the protocols were established by the excellent compatibility of wide variety of substrates including carbohydrates.展开更多
Rice is one of the three most important food crops in the world.Increasing rice yield is an effective way to ensure food security.Grain size is a key factor affecting rice yield;however,the genetic and molecular mecha...Rice is one of the three most important food crops in the world.Increasing rice yield is an effective way to ensure food security.Grain size is a key factor affecting rice yield;however,the genetic and molecular mechanisms regulating grain size have not been fully investigated.In this study,we identified a rice mutant,wide grain 4-D(wg4-D),that exhibited a significant increase in grain width and a decrease in grain length.Histological analysis demonstrated that WG4 affects cell expansion thereby regulating grain size.MutMap-based gene mapping and complementary transgenic experiments revealed that WG4 encodes an alpha-tubulin,OsTubA1.A SNP mutation in WG4 affected the arrangement of cortical microtubules and caused a wide-grain phenotype.WG4 is located in nuclei and cytoplasm and expressed in various tissues.Our results provide insights into the function of tubulin in rice and identifies novel targets the regulation of grain size in crop breeding.展开更多
Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report...Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.展开更多
BACKGROUND Early control of low-density lipoprotein cholesterol(LDL-C)is crucial for reducing the progress of cardiovascular disease.However,its additional role to the risk of primary osteoporosis in men with coronary...BACKGROUND Early control of low-density lipoprotein cholesterol(LDL-C)is crucial for reducing the progress of cardiovascular disease.However,its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive.Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China.METHODS The retrospective cohort study of 1546 men aged 69.74±11.30 years conducted in Beijing,China from 2015 to 2022.And the incidence of primary osteoporosis was annually recorded.LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C.The association of baseline LDL-C for osteoporosis was estimated using hazard ratio(HR)with 95%CI in Cox proportional hazard model,while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio(OR)with 95%CI in logistic regression model.RESULTS During the median 6.2-year follow-up period,70 men developed primary osteoporosis.The higher level of baseline LDLC(HR=1.539,95%CI:1.012–2.342)and mean LDL-C(OR=2.190,95%CI:1.443–3.324)were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates.Compared with those in the LDL-C trajectory of low-stable decrease,participants with medium-fluctuant trajectory,whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease,were negatively associated with osteoporosis risk(OR=2.451,95%CI:1.152–5.216).And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk(OR=0.718,95%CI:0.212–2.437).CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men.Early controlling a stable level of LDL-C is also essential for bone health.展开更多
BACKGROUND Endoscopic retrograde appendicitis therapy(ERAT)offers an appendix-pre-serving approach;however,visual and specificity challenges persist.Conversely,endoscopic direct appendicitis therapy(EDAT)provides dire...BACKGROUND Endoscopic retrograde appendicitis therapy(ERAT)offers an appendix-pre-serving approach;however,visual and specificity challenges persist.Conversely,endoscopic direct appendicitis therapy(EDAT)provides direct visual observation with diagnostic and therapeutic capabilities.AIM To assess the efficacy and feasibility of EDAT and compare them with those of ERAT in uncomplicated appendicitis.METHODS In this retrospective cohort study,patients diagnosed with uncomplicated appendicitis and treated with ERAT or EDAT between January 2021 and November 2024 were reviewed.The primary outcome was intervention success.Secondary outcomes were guidewire use,stent placement,hospitalization duration,recurrence,and endoscopic direct-view features.Outcomes were compared between groups via appropriate statistical tests.RESULTS Of 170 patients,136 underwent EDAT and 34 ERAT.EDAT showed higher intervention success than ERAT(99.3%vs 82.4%,P<0.001),with less guidewire assistance and fewer stent placements(both P<0.001).Hospital stay was shorter with EDAT(P=0.039).The overall cumulative recurrence rates at 1 year were 10%in EDAT and 24%in ERAT;in the appendicolith subgroup,the recurrence rates were 5%and 14%in EDAT and ERAT,respectively.Findings were consistent in the propensity score-matched(PSM)cohort.CONCLUSION EDAT was demonstrated to be a more effective and feasible approach than ERAT,with a lower overall cumulative recurrence risk and within the appendicolith subgroup.Consistent results after PSM further supported the robustness of these findings.展开更多
Lishiite,(Ca_(2)□)Sr_(3)(CO_(3))_(5),is a new mineral species from Shaxiongdong,Hubei Province,China.It mainly occours as conchoidal crystals and with combination of hexagonal prism and pyramid and is associated with...Lishiite,(Ca_(2)□)Sr_(3)(CO_(3))_(5),is a new mineral species from Shaxiongdong,Hubei Province,China.It mainly occours as conchoidal crystals and with combination of hexagonal prism and pyramid and is associated with calcite,K-feldspar,albite,aegirine,apatite,and ancylite-(Ce)(?)and strontianite etc.Lishiite is brittle with conchiform fracture and has a Mohs hardness of approximately 4 and none cleavages were observed.The Vickers microhardness(VHN10)is 197.42 kg/mm^(2)(range:166.88 kg/mm^(2) to 214.58 kg/mm^(2)),and the calculated density of lishiite is 3.696 g/cm3.Hand specimen of lishiite are yellow-brown.The empirical chemical formula of the lishiite is ^(A)(Ca_(1.18)Sr_(0.25)Na_(0.19□1.38))_(Σ3.00)^( B)[Sr_(2.17)(Ce_(0.42)La_(0.24)Nd_(0.09)Eu_(0.01))_(Σ0.76) Ba_(0.07)]_(Σ3.00)(C_(5.05)O_(15)).As a member of the burbankite group,the general formula of lishiite follows the general formula A_(3)B_(3)(CO_(3))_(5),where A=Na,Ca,or and B=Sr,Ba,REE,or Ca.Its crystal structure is hexagonal(space group P6_(3)mc)with unit cell parameters a=10.4898(5)Å,c=6.4167(5)Å,and V=611.47(6)Å^(3),characterized by layers of AO_(8) and BO_(10) polyhedra connected to[CO_(3)]^(3−)groups.The discovery of lishiite provides new insights into the evolutionary history of rare earth element(REE)carbonate deposit formation.展开更多
BACKGROUND Older patients often experience thirst after general anesthesia for gastrointestinal surgery,particularly during the post-anesthesia care unit(PACU)phase.Thirst not only compromises patient comfort but also...BACKGROUND Older patients often experience thirst after general anesthesia for gastrointestinal surgery,particularly during the post-anesthesia care unit(PACU)phase.Thirst not only compromises patient comfort but also induces anxiety,which may hinder recovery.Although previous studies have addressed postoperative thirst,research specifically examining thirst experiences and nursing needs in older patients remains limited.AIM To explore thirst experiences and nursing needs of older PACU patients following gastrointestinal surgery,aiming to inform targeted interventions.METHODS This study employed a phenomenological approach within a qualitative research framework.A purposeful sampling method was used to select 12 older patients who underwent gastrointestinal surgery under general anesthesia at a tertiary hospital in Shanghai between November and December 2024.Data were collected through semi-structured interviews and analyzed using Colaizzi’s seven-step method.Themes were extracted from the interview data.RESULTS Analysis of the interview data identified four main themes and eight subthemes:(1)Intense sensations of thirst post-surgery(subjective experience of thirst and duration of thirst);(2)Emotional experiences of thirst-related discomfort(anxiety,irritability,and helplessness);(3)Practical challenges in relieving thirst(limitations of current interventions and nursing response time);and(4)Patient expectations of nursing care(desire for more timely interventions and expectation for more proactive attention from nursing staff).CONCLUSION Older patients frequently experience substantial thirst discomfort after gastrointestinal surgery under general anesthesia.A multidisciplinary perioperative intervention plan is essential to alleviate these symptoms and enhance postoperative comfort.展开更多
BACKGROUND Histoplasmosis is a rare infectious condition with mainly pulmonary involvement which is generally self-limiting in immunocompetent individuals.Its manifestation varies and lacks specificity.This study repo...BACKGROUND Histoplasmosis is a rare infectious condition with mainly pulmonary involvement which is generally self-limiting in immunocompetent individuals.Its manifestation varies and lacks specificity.This study reports a case of primary disseminated liver histoplasmosis in a normal host presenting as liver failure cured by liver transplantation and voriconazole.CASE SUMMARY A 43-year-old Chinese man with intermittent fever,malaise,jaundice and extreme hepatomegaly for more than 40 days was admitted to the Second Xiang-ya Hospital.The patient was immunocompetent and lacked a definitive history of exposure.His condition deteriorated to liver failure,and he promptly underwent liver transplantation to ensure survival.One year later,the patient presented with severe gastrointestinal symptoms,including fever,abdominal pain,and diarrhea.Subsequently,tissue samples acquired via gastrointestinal endoscopy were subjected to pathological examination and next-generation sequencing analysis.Through a comprehensive amalgamation of clinical presentation,biopsy pathology,and next-generation sequencing analysis,the patient was ultimately diagnosed with disseminated hepatic histoplasmosis.The patient achieved complete recovery after 6 months of voriconazole treatment.CONCLUSION In patients with chronic-hepatitis-B having atypical symptoms,histoplasmosis can be a differential diagnosis.Voriconazole is effective in treating histoplasmosis.展开更多
In this editorial we comment on the article by Jiang et al.We focus on the Ence-phalApp Stroop test which is an innovative,smartphone-based tool specifically designed for screening minimal hepatic encephalopathy(MHE)i...In this editorial we comment on the article by Jiang et al.We focus on the Ence-phalApp Stroop test which is an innovative,smartphone-based tool specifically designed for screening minimal hepatic encephalopathy(MHE)in cirrhosis patients.Traditional MHE screening methods,while highly sensitive and specific,are often complex,time-consuming,and require controlled environmental con-ditions,limiting their widespread clinical use.The EncephalApp Stroop test si-mplifies the screening process,enhances diagnostic efficiency,and is applicable across diverse cultural contexts.However,the combination of additional bio-markers could further improve diagnostic accuracy.Despite its promising po-tential,more multicenter clinical studies are required to validate its effectiveness and applicability on a global scale.展开更多
Prostate cancer(PCa)is a leading cause of cancer-related mortality among men.Radiotherapy is the cornerstone of PCa treatment.However,a major limitation of radiotherapy is the development of resistance,which compromis...Prostate cancer(PCa)is a leading cause of cancer-related mortality among men.Radiotherapy is the cornerstone of PCa treatment.However,a major limitation of radiotherapy is the development of resistance,which compromises treatment efficacy.Reactive oxygen species(ROS),which are generated by radiation,have a dual role in PCa by inducing DNA damage and apoptosis,while also promoting tumor progression and radioresistance.Elevated ROS levels enhance metabolic reprogramming,activate oncogenic pathways,and influence the tumor microenvironment by modulating immune responses and promoting the epithelial-mesenchymal transition(EMT).Key molecular mechanisms,including the Nrf2/Keap1 signaling axis,Bcl-2 mutations,and Speckle-type POZ protein alterations,contribute to radioresistance by enhancing antioxidant defenses and DNA repair capacity.Additionally,the interplay between hypoxia,androgen receptor variants(AR-Vs),and ferroptosis regulators further influence radiotherapy outcomes.Understanding these resistance mechanisms is crucial for developing targeted strategies to enhance radiosensitivity and improve therapeutic outcomes in PCa patients.展开更多
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 grants from the National Key Re-search and Development Program of China(2023YFC3603100 and 2023YFC3603105)“Leading Goose”R&D Program of Zhejiang Province(2022C03076-4).
文摘Background:Diquat,a commonly employed bipyridyl herbicide,is recognized for its hepatotoxic effects attributed to the generation of reactive oxygen species.Baicalin(BAI),a flavonoid derivative,has garnered significant research interest for its hepatoprotective properties.Nevertheless,the clinical application of BAI is constrained by its limited water solubility and poor bioavailability.To address these challenges,BAI-nanoliposome(BAI-NL)has emerged as a novel drug delivery platform aimed at enhancing therapeutic outcomes.Methods:We used diquat-induced liver injury mouse model and AML12 hepatocytes to test the pro-tective effect of BAI and BAI-NL on liver inflammation,oxidative stress,and mitochondrial function.The parameters included histological,biochemical,and molecular biological analyses.Results:In the diquat-induced model,both BAI and BAI-NL exhibited effectiveness on attenuating liver inflammation.Ex vivo analyses further indicated that BAI-NL was superior to BAI in preserving mito-chondrial membrane potential,reducing oxidative stress,and modulating the phosphatase and tensin homolog-induced putative kinase 1(PINK1)/Parkin RBR E3 ubiquitin-protein ligase(Parkin)signaling pathway.These findings enhanced mitophagy and facilitated the removal of damaged mitochondria.Conclusions:BAI-NL exhibited superior hepatoprotective effects compared to free BAI,possibly by re-ducing inflammation,preserving mitochondrial homeostasis,and reinstating autophagic balance through modulation of the PINK1/Parkin signaling pathway.These outcomes indicate a groundbreaking method for addressing liver diseases and underscore the potential of nanoliposome technology in augmenting the efficacy of natural compounds.
基金supported by National Natural Science Foun-dation of China (Nos. 21637003 and 41977338)。
文摘Here we reported an effective method to solve the rate-limiting steps, such as the reduction of Fe^(3+) to Fe^(2+) and an invalid decomposition of H2O2 in a conventional Fenton-like reaction. A magnetic heterogeneous photocatalyst, Fe3O4-schwertmannite(Fe3O4-sch) was successfully developed by adding Fe3O4 in the formation process of schwertmannite. Fe3O4-sch shows excellent electrons transfer ability and high utilization efficiency of H2O2(98.5%). The catalytic activity of Fe3O4-sch was studied through the degradation of phenol in the heterogeneous photo-Fenton process. Phenol degradation at a wide pH(3-9) was up to 98% within 6 min under visible light illumination with the Fe3O4-sch as heterogeneous Fenton catalyst, which was higher than that using pure schwertmannite or Fe3O4. The excellent photocatalytic performance of Fe3O4-sch is ascribed to the effective recycling between ≡Fe^(3+) and ≡Fe^(2+) by the photo-generated electron, and also profit from the formation of the "Z-Scheme" system. According to the relevant data, photocatalytic mechanism of Fe3O4-sch for degrading phenol was proposed. This study not only provides an efficient way of enhancing heterogeneous Fenton reaction, but also gives potential application for iron oxyhydroxysulfate mineral.
基金supported by grants from the National Natural Science Foundation of China (91749118, 82070807, 81770775, 81730022)Natural Science Foundation of Hunan Province, China (2021JJ30976)National Key Research and Development Program (2019YFA0801903, 2018YFC2000100)。
文摘Decreased functional β-cell mass is the hallmark of diabetes, but the cause of this metabolic defect remains elusive. Here, we show that the levels of the growth factor receptor-bound protein 10(GRB10), a negative regulator of insulin and m TORC1 signaling, are markedly induced in islets of diabetic mice and high glucose-treated insulinoma cell line INS-1 cells. β-cell-specific knockout of Grb10 in mice increased β-cell mass and improved β-cell function. Grb10-deficient β-cells exhibit enhanced m TORC1 signaling and reduced β-cell dedifferentiation, which could be blocked by rapamycin. On the contrary, Grb10 overexpression induced β-cell dedifferentiation in MIN6 cells. Our study identifies GRB10 as a critical regulator of β-cell dedifferentiation and β-cell mass, which exerts its effect by inhibiting m TORC1 signaling.
基金supported by Shandong Provincial Natural Science Foundation General Program(No.ZR2022MH213)Shandong Provincial Traditional Chinese Medicine Science and Technology Project General Program(No.M2023241)+1 种基金Jinan Clinical Medical Science and Technology Innovation Program(No.202328013)Qinghai Province High-end Innovative Talents Thousand Talents Program.
文摘Objective Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs;however,concerns regarding complexities and side effects persist,driving research for more effective,low-risk strategies.The promotion of white adipose tissue(WAT)browning has emerged as a promising approach.Moreover,alisol B 23-acetate(AB23A)has demonstrated efficacy in addressing metabolic disorders,suggesting its potential as a therapeutic agent in obesity management.Therefore,in this study,we aimed to investigate the therapeutic potential of AB23A for mitigating obesity by regulating metabolic phenotypes and lipid distribution in mice fed a high-fat diet(HFD).Methods An obesity mouse model was established by administration of an HFD.Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests.Adipocyte size was determined using hematoxylin and eosin staining.The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction.Metabolic cage monitoring involved the assessment of various parameters,including food and water intake,energy metabolism,respiratory exchange rates,and physical activity.Moreover,oil red O staining was used to evaluate intracellular lipid accumulation.A bioinformatic analysis tool for identifying the molecular mechanisms of traditional Chinese medicine was used to examine AB23A targets and associated signaling pathways.Results AB23A administration significantly reduced the weight of obese mice,decreased the mass of inguinal WAT,epididymal WAT,and perirenal adipose tissue,improved glucose and insulin metabolism,and reduced adipocyte size.Moreover,treatment with AB23A promoted the expression of browning markers in WAT,enhanced overall energy metabolism in mice,and had no discernible effect on food intake,water consumption,or physical activity.In 3T3-L1 cells,AB23A inhibited lipid accumulation,and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulatory element-binding protein-1(mTOR-SREBP1)signaling pathway.Furthermore,3-isobutyl-1-methylxanthine,dexamethasone and insulin,at concentrations of 0.25 mmol/L,0.25μmol/L and 1μg/mL,respectively,induced activation of the mTOR-SREBP1 signaling pathway,which was further strengthened by an mTOR activator MHY1485.Notably,MHY1485 reversed the beneficial effects of AB23A in 3T3-L1 cells.Conclusion AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway,offering a potential strategy to prevent obesity.
基金supported by the National Natural Science Foundation of China(82070593)the Zhejiang Provincial Natural Science Foundation(LD21H030002)+1 种基金the Department of Science and Technology of Zhejiang Province(ZY2019008)the Youth Program of the National Natural Science Foundation of China(82200632).
文摘One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of diagnosis.The relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors.Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse models.Moreover,there is a direct relationship between pIgR expression and transaminase levels in patients with AIH.In this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH.Reg3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota disruption.Conversely,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis.RNA sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through pIgR.Furthermore,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in AIH.Through this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.
文摘Objective:To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer patients with indications for breast cancer susceptibility genes 1/2(BRCA1/2)genetic testing in China.Methods:Based on the indication criteria for BRCA genetic testing specified in the National Comprehensive Cancer Network(NCCN)clinical practice guidelines in oncology,genetic/familial high-risk assessment:Breast and ovarian(Version 2.2019),a retrospective analysis was performed on patients with early-stage invasive breast cancer treated at Breast Disease Center,Peking University First Hospital between January 2008 and December 2016.Clinicopathological characteristics of all patients were analyzed,and prognoses were calculated using the KaplanMeier method and a Cox proportionate hazards model.Results:A total of 906 early-stage breast cancer patients who had indications for BRCA genetic testing and had complete clinicopathological data and follow-up information were included in the study group,accounting for34.7%of all breast cancer patients treated in Breast Disease Center,Peking University First Hospital during the study period.Compared with breast cancer patients without indications for BRCA genetic testing,the overall survival(OS)and disease-free survival(DFS)of patients with indications were not significantly different.In the study group,patients with premenopausal status,high T stage,lymph node positive,estrogen receptor(ER)negative,Ki-67>20%and presence of a vascular tumor thrombus had worse prognosis.There were more family histories of gastrointestinal cancer in patients with related indications than in patients without such indications.Conclusions:Single-center data showed that more than 30%of patients with early-stage breast cancer had indications for BRCA genetic testing.There was no prognostic difference in patients with or without indications for BRCA genetic testing.Premenopausal status,high T stage,lymph node positive,ER negative,Ki-67>20%,and presence of a vascular tumor thrombus were associated with poor prognosis.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.61773091,61603073,61601081,and 61501107)the Natural Science Foundation of Liaoning Province,China(Grant No.201602200)
文摘The emergence of Event-based Social Network(EBSN) data that contain both social and event information has cleared the way to study the social interactive relationship between the virtual interactions and physical interactions. In existing studies, it is not really clear which factors affect event similarity between online friends and the influence degree of each factor. In this study, a multi-layer network based on the Plancast service data is constructed. The the user’s events belongingness is shuffled by constructing two null models to detect offline event similarity between online friends. The results indicate that there is a strong correlation between online social proximity and offline event similarity. The micro-scale structures at multi-levels of the Plancast online social network are also maintained by constructing 0 k–3 k null models to study how the micro-scale characteristics of online networks affect the similarity of offline events. It is found that the assortativity pattern is a significant micro-scale characteristic to maintain offline event similarity. Finally, we study how structural diversity of online friends affects the offline event similarity. We find that the subgraph structure of common friends has no positive impact on event similarity while the number of common friends plays a key role, which is different from other studies. In addition, we discuss the randomness of different null models, which can measure the degree of information availability in privacy protection. Our study not only uncovers the factors that affect offline event similarity between friends but also presents a framework for understanding the pattern of human mobility.
基金National Natural Science Foundation of China(Nos.22374116,22074118,82174088)Natural Science Basic Research Program of Shaanxi(2024JC-TBZC-21)Shaanxi Administration of Traditional Chinese Medicine(No.2022-SLRH-YQ-007)。
文摘GPCRs are dominant targets for approved drugs and the discovery of lead compound targeting them is still challengeable.Affinity-based screening technique is a promising platform to uncover GPCR ligands.However,the intrinsic activities of them are seldom simultaneously determined during the screening.Taking beta2-adrenoceptor(β2AR)as a probe,this work created a strategy for screening GPCR ligands with simultaneous characterization of their downstream G protein binding responses associated with GTP.The strategy included(i)the design and expression of a protein miniature formed byβ2AR and G proteinα-subunit(Gαs)using circularly permuted HaloTag(cpHalo)as a flexible linker;(ii)immobilization of the miniature onto silica gel by a click dehalogenation reaction;(iii)systematic characterization of the immobilized miniature by fluorescent and chromatographic studies,and(iv)simulating of ligand-inducedβ2AR-Gαs signaling cascade by chromatographic assays using GTP as an indicator.The immobilized miniature exhibited specificity toβ2AR and Gαs antibodies and ligands.The specificity is stable at least within fifteen days with the variation less than 1%.The intrinsic activities ofβ2AR ligands were distinguished by the changes of GTP chromatographic behaviors on Gαs-cpHalo-β2AR column.Agonists strengthened the binding affinity and kinetics of GTP with Gαs,while antagonist did not give any effect on them.With the intrinsic activity evaluation,we believe,it will improve the attributes of chromatographic methods for drug discovery efforts with minimizing false-positive results.
基金financial support from the National Natural Science Foundation of China(Nos.U1736201,21677019 and 41403021)Capital Health Research and Development of Special(No.2018-4-1014)the Key Research and Development Program of Beijing(No.D171100008317001)。
文摘Here,a new designed core/satellite gold nanoprobe was developed for detecting trace mount of benzoyl peroxide(BPO) based on its deboronation.This gold nanoassembly(the BE-Au NPs_(12/65)) wa s constructed via borate ester formation between large 4-mercaptophenylboronic acid(MPBA) modified Au NPs(the MPBAAu NPs_(65),as cores) and small dopamine modified AuNPs(the D PA-AuNPs_(12),as satellites).Particularly,upon addition of BPO,it would trigger the deboronation for the BE-AuNPs_(12/65) probes accompanying with distinct color changes from blue,purple to wine red,which implied the disassembly of the core/satellite nanostructure after the breakage of carbon to boron chemical bond.By measuring the absorbance ratio at 665 nm and 545 nm,quantification of BPO was achieved in the range of 10.0-100.0 nmol/L,which could also be easily observed by naked eyes.The nanoprobe utilized a boronate deprotection mechanism and the LSPR properties of Au NPs to provide high selectivity for detecting BPO over similar ROS/RNS with the limit of detection as low as 7.2 nmol/L.The practical applicability of this assay was verified through successful determining BPO in flour samples,which demonstrated its great potentials in food safety field.
基金Financial support from National Natural Science Foundation of China(Nos.21877043,21702068,21772050,22025102)the Fundamental Research Funds for the Central Universities,HUST(Nos.2019kfyXKJC080,2019JYCXJJ046)Huazhong University of Science and Technology are greatly appreciated。
文摘A sulfonium ylide participated alkylation and arylation under transition-metal free conditions is described.The disparate reaction pattern allowed the separate activation of non-ylidic S-alkyl and S-aryl bond.Under acidic conditions,sulfonium ylides serve as alkyl cation precursors which facilitate the alkylations.While under alkaline conditions,cleavage of non-ylidic S-aryl bond produces O-arylated compounds efficiently.The robustness of the protocols were established by the excellent compatibility of wide variety of substrates including carbohydrates.
基金the National Natural Science Foundation of China(32121003),the Sichuan Science and Technology Program(2022ZDZX0012,2022YFQ0026)the Natural Science Foundation of Sichuan province(2022NSFSC1667).
文摘Rice is one of the three most important food crops in the world.Increasing rice yield is an effective way to ensure food security.Grain size is a key factor affecting rice yield;however,the genetic and molecular mechanisms regulating grain size have not been fully investigated.In this study,we identified a rice mutant,wide grain 4-D(wg4-D),that exhibited a significant increase in grain width and a decrease in grain length.Histological analysis demonstrated that WG4 affects cell expansion thereby regulating grain size.MutMap-based gene mapping and complementary transgenic experiments revealed that WG4 encodes an alpha-tubulin,OsTubA1.A SNP mutation in WG4 affected the arrangement of cortical microtubules and caused a wide-grain phenotype.WG4 is located in nuclei and cytoplasm and expressed in various tissues.Our results provide insights into the function of tubulin in rice and identifies novel targets the regulation of grain size in crop breeding.
基金supported by the National Natural Science Foundation of China,Nos.82171429,81771384a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。
文摘Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.
基金supported by the Multi-center RCT Clinical Project of the National Clinical Research Center for Geriatric Diseases,Chinese PLA General Hospital(NCRCGPLAGH-2023001)the Beijing Nova Program(No.20220484020)+1 种基金the Beijing Natural Science Foundation(No.7252181)the Capital’s Funds for Health Improvement and Research(No.2024-2G-5033).
文摘BACKGROUND Early control of low-density lipoprotein cholesterol(LDL-C)is crucial for reducing the progress of cardiovascular disease.However,its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive.Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China.METHODS The retrospective cohort study of 1546 men aged 69.74±11.30 years conducted in Beijing,China from 2015 to 2022.And the incidence of primary osteoporosis was annually recorded.LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C.The association of baseline LDL-C for osteoporosis was estimated using hazard ratio(HR)with 95%CI in Cox proportional hazard model,while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio(OR)with 95%CI in logistic regression model.RESULTS During the median 6.2-year follow-up period,70 men developed primary osteoporosis.The higher level of baseline LDLC(HR=1.539,95%CI:1.012–2.342)and mean LDL-C(OR=2.190,95%CI:1.443–3.324)were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates.Compared with those in the LDL-C trajectory of low-stable decrease,participants with medium-fluctuant trajectory,whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease,were negatively associated with osteoporosis risk(OR=2.451,95%CI:1.152–5.216).And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk(OR=0.718,95%CI:0.212–2.437).CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men.Early controlling a stable level of LDL-C is also essential for bone health.
基金Supported by Guangdong Province Clinical Teaching Base Teaching Reform Research Project,No.2021JD086.
文摘BACKGROUND Endoscopic retrograde appendicitis therapy(ERAT)offers an appendix-pre-serving approach;however,visual and specificity challenges persist.Conversely,endoscopic direct appendicitis therapy(EDAT)provides direct visual observation with diagnostic and therapeutic capabilities.AIM To assess the efficacy and feasibility of EDAT and compare them with those of ERAT in uncomplicated appendicitis.METHODS In this retrospective cohort study,patients diagnosed with uncomplicated appendicitis and treated with ERAT or EDAT between January 2021 and November 2024 were reviewed.The primary outcome was intervention success.Secondary outcomes were guidewire use,stent placement,hospitalization duration,recurrence,and endoscopic direct-view features.Outcomes were compared between groups via appropriate statistical tests.RESULTS Of 170 patients,136 underwent EDAT and 34 ERAT.EDAT showed higher intervention success than ERAT(99.3%vs 82.4%,P<0.001),with less guidewire assistance and fewer stent placements(both P<0.001).Hospital stay was shorter with EDAT(P=0.039).The overall cumulative recurrence rates at 1 year were 10%in EDAT and 24%in ERAT;in the appendicolith subgroup,the recurrence rates were 5%and 14%in EDAT and ERAT,respectively.Findings were consistent in the propensity score-matched(PSM)cohort.CONCLUSION EDAT was demonstrated to be a more effective and feasible approach than ERAT,with a lower overall cumulative recurrence risk and within the appendicolith subgroup.Consistent results after PSM further supported the robustness of these findings.
基金supported by the project China Geological Survey(DD202501026090)the National Key Research and Development Program of China(2024YFC2910102).
文摘Lishiite,(Ca_(2)□)Sr_(3)(CO_(3))_(5),is a new mineral species from Shaxiongdong,Hubei Province,China.It mainly occours as conchoidal crystals and with combination of hexagonal prism and pyramid and is associated with calcite,K-feldspar,albite,aegirine,apatite,and ancylite-(Ce)(?)and strontianite etc.Lishiite is brittle with conchiform fracture and has a Mohs hardness of approximately 4 and none cleavages were observed.The Vickers microhardness(VHN10)is 197.42 kg/mm^(2)(range:166.88 kg/mm^(2) to 214.58 kg/mm^(2)),and the calculated density of lishiite is 3.696 g/cm3.Hand specimen of lishiite are yellow-brown.The empirical chemical formula of the lishiite is ^(A)(Ca_(1.18)Sr_(0.25)Na_(0.19□1.38))_(Σ3.00)^( B)[Sr_(2.17)(Ce_(0.42)La_(0.24)Nd_(0.09)Eu_(0.01))_(Σ0.76) Ba_(0.07)]_(Σ3.00)(C_(5.05)O_(15)).As a member of the burbankite group,the general formula of lishiite follows the general formula A_(3)B_(3)(CO_(3))_(5),where A=Na,Ca,or and B=Sr,Ba,REE,or Ca.Its crystal structure is hexagonal(space group P6_(3)mc)with unit cell parameters a=10.4898(5)Å,c=6.4167(5)Å,and V=611.47(6)Å^(3),characterized by layers of AO_(8) and BO_(10) polyhedra connected to[CO_(3)]^(3−)groups.The discovery of lishiite provides new insights into the evolutionary history of rare earth element(REE)carbonate deposit formation.
文摘BACKGROUND Older patients often experience thirst after general anesthesia for gastrointestinal surgery,particularly during the post-anesthesia care unit(PACU)phase.Thirst not only compromises patient comfort but also induces anxiety,which may hinder recovery.Although previous studies have addressed postoperative thirst,research specifically examining thirst experiences and nursing needs in older patients remains limited.AIM To explore thirst experiences and nursing needs of older PACU patients following gastrointestinal surgery,aiming to inform targeted interventions.METHODS This study employed a phenomenological approach within a qualitative research framework.A purposeful sampling method was used to select 12 older patients who underwent gastrointestinal surgery under general anesthesia at a tertiary hospital in Shanghai between November and December 2024.Data were collected through semi-structured interviews and analyzed using Colaizzi’s seven-step method.Themes were extracted from the interview data.RESULTS Analysis of the interview data identified four main themes and eight subthemes:(1)Intense sensations of thirst post-surgery(subjective experience of thirst and duration of thirst);(2)Emotional experiences of thirst-related discomfort(anxiety,irritability,and helplessness);(3)Practical challenges in relieving thirst(limitations of current interventions and nursing response time);and(4)Patient expectations of nursing care(desire for more timely interventions and expectation for more proactive attention from nursing staff).CONCLUSION Older patients frequently experience substantial thirst discomfort after gastrointestinal surgery under general anesthesia.A multidisciplinary perioperative intervention plan is essential to alleviate these symptoms and enhance postoperative comfort.
文摘BACKGROUND Histoplasmosis is a rare infectious condition with mainly pulmonary involvement which is generally self-limiting in immunocompetent individuals.Its manifestation varies and lacks specificity.This study reports a case of primary disseminated liver histoplasmosis in a normal host presenting as liver failure cured by liver transplantation and voriconazole.CASE SUMMARY A 43-year-old Chinese man with intermittent fever,malaise,jaundice and extreme hepatomegaly for more than 40 days was admitted to the Second Xiang-ya Hospital.The patient was immunocompetent and lacked a definitive history of exposure.His condition deteriorated to liver failure,and he promptly underwent liver transplantation to ensure survival.One year later,the patient presented with severe gastrointestinal symptoms,including fever,abdominal pain,and diarrhea.Subsequently,tissue samples acquired via gastrointestinal endoscopy were subjected to pathological examination and next-generation sequencing analysis.Through a comprehensive amalgamation of clinical presentation,biopsy pathology,and next-generation sequencing analysis,the patient was ultimately diagnosed with disseminated hepatic histoplasmosis.The patient achieved complete recovery after 6 months of voriconazole treatment.CONCLUSION In patients with chronic-hepatitis-B having atypical symptoms,histoplasmosis can be a differential diagnosis.Voriconazole is effective in treating histoplasmosis.
基金Supported by The Basic and Clinical Integration Project of Xi'an Jiaotong University,No.YXJLRH2022067.
文摘In this editorial we comment on the article by Jiang et al.We focus on the Ence-phalApp Stroop test which is an innovative,smartphone-based tool specifically designed for screening minimal hepatic encephalopathy(MHE)in cirrhosis patients.Traditional MHE screening methods,while highly sensitive and specific,are often complex,time-consuming,and require controlled environmental con-ditions,limiting their widespread clinical use.The EncephalApp Stroop test si-mplifies the screening process,enhances diagnostic efficiency,and is applicable across diverse cultural contexts.However,the combination of additional bio-markers could further improve diagnostic accuracy.Despite its promising po-tential,more multicenter clinical studies are required to validate its effectiveness and applicability on a global scale.
基金supported by grants from Ningbo Yongjiang Talent programme-Project for Innovative Talents(Grant No.20240340)Jinhua Science and Technology Bureau(Grant No.2022-4-258)2022 Shandong Medical Association Clinical Research Special Fund for Dynamic Monitoring of Lymphocyte Subpopulations by Flow Cytometry(Grant No.YXH2022ZX03227)。
文摘Prostate cancer(PCa)is a leading cause of cancer-related mortality among men.Radiotherapy is the cornerstone of PCa treatment.However,a major limitation of radiotherapy is the development of resistance,which compromises treatment efficacy.Reactive oxygen species(ROS),which are generated by radiation,have a dual role in PCa by inducing DNA damage and apoptosis,while also promoting tumor progression and radioresistance.Elevated ROS levels enhance metabolic reprogramming,activate oncogenic pathways,and influence the tumor microenvironment by modulating immune responses and promoting the epithelial-mesenchymal transition(EMT).Key molecular mechanisms,including the Nrf2/Keap1 signaling axis,Bcl-2 mutations,and Speckle-type POZ protein alterations,contribute to radioresistance by enhancing antioxidant defenses and DNA repair capacity.Additionally,the interplay between hypoxia,androgen receptor variants(AR-Vs),and ferroptosis regulators further influence radiotherapy outcomes.Understanding these resistance mechanisms is crucial for developing targeted strategies to enhance radiosensitivity and improve therapeutic outcomes in PCa patients.
