The role of osteoblast(OB)autophagy in regulating bone metabolism is a research hotspot in the field of biomedicine.OB autophagy can regulate osteoporosis(OP)induced by aging,oxidative stress,estrogen deficiency,and glucocorticoids(GCs)by mediating factors such as run and cysteine rich domain containing Beclin-1 interacting protein(RUBCN),silent information regulator of transcription 1(SIRT1),and osteoprotegerin(OPG).OB autophagy can also regulate OP by activating notch receptor(Notch)and forkhead box protein O subfamily(FoxO),up-regulating the expression of osteogenic transcription factors(such as Runx2 and Osterix),and mediating the amp-activated protein kinase(AMPK),mammalian target of rapamycin complex(mTOR),Wnt,and c-Jun n terminal kinase(JNK)pathways to act on OB and osteoclast(OC)differentiation.Exercise is an important means of improving OP,and its molecular mechanism is closely related to the up-regulation of phosphatidylinositol 3 kinase(PI3K),adenosine monophosphate(AMP),tumor necrosis factor-alpha(TNF-α),and SIRT1 expression.These in turn activate key factors or pathways(including AMPK,mTOR,Wnt,PI3K/protein kinase B(Akt)/mTOR,and nuclear transcription factor-KB(NF-κB)),regulate the expression of downstream target genes(β-catenin,mTOR,FoxO3a and B cell lymphoma-2(Bcl-2))to up-regulate the expression of autophagy factors(Beclin-1,autophagy related genes(ATG),and microtubule-associated protein 1 light chain 3(LC3)),and promote OB autophagy to restore the dynamic balance in the body,thereby regulating bone formation and bone resorption and improving OP.The relationships among exercise,OB autophagy and OP,however,remain unclear and there is currently a lack of systematic reviews.Here we review and analyze the mechanism of OB autophagy in relation to exercise-induced improvements in OP,and provide a new theoretical basis and research ideas for the prevention and treatment of OP.

The role of osteoblast(OB)autophagy in regulating bone metabolism is a research hotspot in the field of biomedicine.OB autophagy can regulate osteoporosis(OP)induced by aging,oxidative stress,estrogen deficiency,and glucocorticoids(GCs)by mediating factors such as run and cysteine rich domain containing Beclin-1 interacting protein(RUBCN),silent information regulator of transcription 1(SIRT1),and osteoprotegerin(OPG).OB autophagy can also regulate OP by activating notch receptor(Notch)and forkhead box protein O subfamily(FoxO),up-regulating the expression of osteogenic transcription factors(such as Runx2 and Osterix),and mediating the amp-activated protein kinase(AMPK),mammalian target of rapamycin complex(mTOR),Wnt,and c-Jun n terminal kinase(JNK)pathways to act on OB and osteoclast(OC)differentiation.Exercise is an important means of improving OP,and its molecular mechanism is closely related to the up-regulation of phosphatidylinositol 3 kinase(PI3K),adenosine monophosphate(AMP),tumor necrosis factor-alpha(TNF-α),and SIRT1 expression.These in turn activate key factors or pathways(including AMPK,mTOR,Wnt,PI3K/protein kinase B(Akt)/mTOR,and nuclear transcription factor-KB(NF-κB)),regulate the expression of downstream target genes(β-catenin,mTOR,FoxO3a and B cell lymphoma-2(Bcl-2))to up-regulate the expression of autophagy factors(Beclin-1,autophagy related genes(ATG),and microtubule-associated protein 1 light chain 3(LC3)),and promote OB autophagy to restore the dynamic balance in the body,thereby regulating bone formation and bone resorption and improving OP.The relationships among exercise,OB autophagy and OP,however,remain unclear and there is currently a lack of systematic reviews.Here we review and analyze the mechanism of OB autophagy in relation to exercise-induced improvements in OP,and provide a new theoretical basis and research ideas for the prevention and treatment of OP.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

Objective To establish a method for the simultaneous determination of 16 cephalosporin antibiotics of the fourth generation in whole blood by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),including representative drugs such as cefalexin,cefuroxime axetil,cefetamet pivoxil,ceftizoxime,cefodizime,cefteram pivoxil,cefpodoxime proxetil,cefditoren pivoxil,cefminox sodium,cefoperazone,cefpirome,cefoxitin,cefamandole nafate,cefquinome sulfate,cefpiramide,and ceftiofur.Methods Whole blood was pretreated with acetonitrile for protein precipitation and then determined by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry.The liquid phase used a Hypersil GOLD? C18 column(2.1 mm ×100 mm,1.9 μm).The organic phase was 0.1％formic acid methanol solution,and the aqueous phase was 0.1％formic acid aqueous solution(containing 10 mmol/mL ammonium formate)for gradient elution.Detection was performed in electrospray positive ionization mode with selected reaction monitoring(SRM).Results The 16 drugs showed good linearity within their respective concentration ranges,with R2 values all greater than 0.99.Limits of detection for cefminox sodium and cefpiramide were 50 and 20 ng/mL,respectively,and for the remaining 14 drugs were all lower than 5 ng/mL.The relative standard deviations(RSDs)of intra-day and inter-day precisions at four spiked concentrations for the 16 drugs were all no higher than 10％(n=5).Accuracy ranged within±15％for mosg drugs,except for cefamandole nafate,ceftiofur,and cefetamet pivoxil at the lower limit of quantification,which showed accuracy within±20％.Extraction recoveries exceeded 80％for all compounds.Conclusion This method has high detection sensitivity,rapid speed,and good repeatability for the simultaneously determination of 16 cephalosporin antibiotics in whole blood.

Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

Objective To establish a method for the simultaneous determination of 16 cephalosporin antibiotics of the fourth generation in whole blood by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),including representative drugs such as cefalexin,cefuroxime axetil,cefetamet pivoxil,ceftizoxime,cefodizime,cefteram pivoxil,cefpodoxime proxetil,cefditoren pivoxil,cefminox sodium,cefoperazone,cefpirome,cefoxitin,cefamandole nafate,cefquinome sulfate,cefpiramide,and ceftiofur.Methods Whole blood was pretreated with acetonitrile for protein precipitation and then determined by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry.The liquid phase used a Hypersil GOLD? C18 column(2.1 mm ×100 mm,1.9 μm).The organic phase was 0.1％formic acid methanol solution,and the aqueous phase was 0.1％formic acid aqueous solution(containing 10 mmol/mL ammonium formate)for gradient elution.Detection was performed in electrospray positive ionization mode with selected reaction monitoring(SRM).Results The 16 drugs showed good linearity within their respective concentration ranges,with R2 values all greater than 0.99.Limits of detection for cefminox sodium and cefpiramide were 50 and 20 ng/mL,respectively,and for the remaining 14 drugs were all lower than 5 ng/mL.The relative standard deviations(RSDs)of intra-day and inter-day precisions at four spiked concentrations for the 16 drugs were all no higher than 10％(n=5).Accuracy ranged within±15％for mosg drugs,except for cefamandole nafate,ceftiofur,and cefetamet pivoxil at the lower limit of quantification,which showed accuracy within±20％.Extraction recoveries exceeded 80％for all compounds.Conclusion This method has high detection sensitivity,rapid speed,and good repeatability for the simultaneously determination of 16 cephalosporin antibiotics in whole blood.

Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans ; Cleft Lip/diagnosis* ; Cleft Palate/diagnosis* ; Consensus ; Prenatal Diagnosis ; Female

OBJECTIVES: This study aims to investigate factors influencing dental arch development in patients aged 0-6 years with cleft palate after Sommerlad-Furlow (SF) palatoplasty. METHODS: A total of 183 patients who underwent primary SF repair for cleft lip and palate before 18 months of age were included. Follow-ups were conducted at different ages, and digital dental casts of the maxillary dental arch were obtained using 3-matic Research 12.0 software. The length and width of the dental arch and palate were measured to explore developmental changes in the maxillary dental arch of the patients after the procedure. The study also investigated the influence of gender, age, cleft palate type, and relaxation incision on maxillary dental arch development. RESULTS: After SF, maxillary dental arch measurements showed statistically significant differences between children aged 0-2 years and those aged 3-6 years (P<0.05). However, no statistically significant differences were observed among different age groups within the 3-6 years range. Statistically significant differences were detected between males and females, with males having greater width of the posterior dental arch and palate (P=0.001) and shorter length of the anterior dental arch and entire dental arch (P<0.05). The unilateral cleft lip and palate group had shorter dental arch length (P<0.01) and wider posterior palate (P<0.01) than the cleft palate only group. Maxillary dental arch measurements had no statistically significant differences between groups with or without a relaxing incision. CONCLUSIONS Gender and age influence the width of the maxillary dental arch in children aged 0-6 years after SF, while age and cleft palate type affect dental arch length.
Humans ; Child, Preschool ; Male ; Cleft Palate/surgery* ; Female ; Child ; Infant ; Dental Arch/growth & development* ; Maxilla/growth & development* ; Cleft Lip/surgery* ; Age Factors ; Sex Factors ; Palate/surgery* ; Infant, Newborn

Objective To investigate the effect of early use of ivabradine on cardiac function in patients with acute myocardial infarction(AMI)after percutaneous coronary intervention(PCI).Methods Eighty patients with AMI who were hospitalized in our hospital from Feb.2020 to May 2021 were enrolled,and were randomly assigned to ivabradine group or control group(1∶1).All patients were successfully treated with emergency PCI,and the ivabradine group was treated with ivabradine combined with metoprolol after PCI,while the control group was treated with metoprolol only.Both groups were followed up for 1 year.Echocardiography-derived parameters,heart rate and myocardial markers were analyzed.Results The left ventricular ejection fraction was significantly higher in the ivabradine group than in the control group at 1 week,3 months,and 1 year after PCI(all P＜0.05).The heart rate of the ivabradine group was significantly lower than that of the control group at 1 week after PCI(P＜0.05),while there was no significant difference in heart rates between the 2 groups at 3 months or 1 year after PCI(both P＞0.05).The brain natriuretic peptide of the ivabradine group was significantly lower than that of the control group on day 2 and day 3 after PCI(both P＜0.05).The troponin Ⅰ level of the ivabradine group was significantly lower than that of the control group on day 5 after PCI(P＜0.05).Conclusion Early use of ivabradine in patients with AMI after PCI can achieve effective heart rate control,reduce myocardial injury and improve cardiac function.

In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not adequately capture the complex biochemical properties of interest. Many proteins and their functions cannot be assessed through high-throughput methods due to technical limitations or the nature of the desired properties, and this is particularly true for the real industrial application scenario. Therefore, the desired testing datasets, will be small-size (∼10-100) experimental data for each protein, and involve as many proteins as possible and as many properties as possible, which is, however, lacking. Here, we present VenusMutHub, a comprehensive benchmark study using 905 small-scale experimental datasets curated from published literature and public databases, spanning 527 proteins across diverse functional properties including stability, activity, binding affinity, and selectivity. These datasets feature direct biochemical measurements rather than surrogate readouts, providing a more rigorous assessment of model performance in predicting mutations that affect specific molecular functions. We evaluate 23 computational models across various methodological paradigms, such as sequence-based, structure-informed and evolutionary approaches. This benchmark provides practical guidance for selecting appropriate prediction methods in protein engineering applications where accurate prediction of specific functional properties is crucial.