Objective To isolate pathogenic bacteria from the skin of a nude mouse exhibiting squamous skin scurfs, and perform bacterial identification, traceability analysis, and pathogenicity studies to provide a new approach for the diagnosis of pathogens in nude mice with squamous skin scurfs. MethodsSkin swab samples were collected from a nude mouse exhibiting squamous skin scurfs for nucleic acid testing, bacterial isolation and culture, biochemical identification, 16S rDNA gene amplification and sequencing, and whole genome sequencing to construct a phylogenetic tree. Fifteen BALB/c nude mice were randomized into a saline-treated control group, a high-concentration group treated with 1.8×10⁸ CFU/mL of the isolated bacterial suspension, and a low-concentration group treated with 1.8×10⁷ CFU/mL of the isolated bacterial suspension. Pathogenicity was assessed by animal infection experiments and observation of histopathological changes in skin tissue using HE staining. Results The nucleic acid test for Corynebacterium bovis was negative, excluding infection by this organism. The pathogen isolated on mannitol salt agar and blood agar, combined with Gram staining, suggested a Gram-positive Staphylococcus species. The isolated strain was identified by 16S rDNA sequencing and a fully automated microbial identification system as Staphylococcus xylosus. Phylogenetic tree analysis based on whole genome sequencing showed that the strain was most closely related to an isolate from leafy vegetables in South Korea (GenBank GCA_00207825.1). In the high-concentration group, squamous skin scurfs appeared on the head, neck, and back of nude mice on the 17th day post-infection, while in the low concentration group, similar symptoms appeared on the 20th day post-infection and gradually spread to other areas. The scaling symptoms were transient, lasting for 7 days in the high-concentration group and 3 days in the low-concentration group, after which the skin returned to normal. The infection rate was 33.33% in both the high- and low-concentration groups. No significant pathological changes were observed in the skin tissues of infected mice compared to the control group, indicating marked individual differences in the pathogenicity of the strain in nude mice. Conclusion A strain of Staphylococcus xylosus was isolated from the skin of a nude mouse exhibiting squamous skin scurfs. The strain is an opportunistic pathogen that causes transient squamous skin scurfs without significant histopathological changes, and there are individual differences in the sensitivity of nude mice to this strain. These findings can provide valuable data for pathogen identification in immunodeficient or gene knockout mice.

Objective To isolate pathogenic bacteria from the skin of a nude mouse exhibiting squamous skin scurfs, and perform bacterial identification, traceability analysis, and pathogenicity studies to provide a new approach for the diagnosis of pathogens in nude mice with squamous skin scurfs. MethodsSkin swab samples were collected from a nude mouse exhibiting squamous skin scurfs for nucleic acid testing, bacterial isolation and culture, biochemical identification, 16S rDNA gene amplification and sequencing, and whole genome sequencing to construct a phylogenetic tree. Fifteen BALB/c nude mice were randomized into a saline-treated control group, a high-concentration group treated with 1.8×10⁸ CFU/mL of the isolated bacterial suspension, and a low-concentration group treated with 1.8×10⁷ CFU/mL of the isolated bacterial suspension. Pathogenicity was assessed by animal infection experiments and observation of histopathological changes in skin tissue using HE staining. Results The nucleic acid test for Corynebacterium bovis was negative, excluding infection by this organism. The pathogen isolated on mannitol salt agar and blood agar, combined with Gram staining, suggested a Gram-positive Staphylococcus species. The isolated strain was identified by 16S rDNA sequencing and a fully automated microbial identification system as Staphylococcus xylosus. Phylogenetic tree analysis based on whole genome sequencing showed that the strain was most closely related to an isolate from leafy vegetables in South Korea (GenBank GCA_00207825.1). In the high-concentration group, squamous skin scurfs appeared on the head, neck, and back of nude mice on the 17th day post-infection, while in the low concentration group, similar symptoms appeared on the 20th day post-infection and gradually spread to other areas. The scaling symptoms were transient, lasting for 7 days in the high-concentration group and 3 days in the low-concentration group, after which the skin returned to normal. The infection rate was 33.33% in both the high- and low-concentration groups. No significant pathological changes were observed in the skin tissues of infected mice compared to the control group, indicating marked individual differences in the pathogenicity of the strain in nude mice. Conclusion A strain of Staphylococcus xylosus was isolated from the skin of a nude mouse exhibiting squamous skin scurfs. The strain is an opportunistic pathogen that causes transient squamous skin scurfs without significant histopathological changes, and there are individual differences in the sensitivity of nude mice to this strain. These findings can provide valuable data for pathogen identification in immunodeficient or gene knockout mice.

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.

AIM:This study explores whether curcumin(Cur)promotes mitophagy to attenuate nonalcoholic steatohepatitis(NASH)in mice,as well as the possible molecular mechanisms involved.METHODS:A high-fat and high-cholesterol diet was used to replicate the NASH mouse model.Thirty-two male C57BL/6J mice were randomly divided into normal control(NC)group,high-fat and high-cholesterol model(M)group,M+low-dose Cur(Cur-L)group,and M+high-dose Cur(Cur-H)group,with 8 mice in each group.The weight of 8 mice in each group was recorded weekly.After feeding for 18 weeks,the serum and liver of mice were collected.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL-C),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and tumor necrosis factors-α(TNF-α)were measured.Liver index was calculated,and steatosis,inflammation,and fibrosis of the liver were observed by HE and Masson staining.Western blot analysis was performed to detect the protein expression of mi-tophagy-related protein,TNF-α and α-SMA in the liver.(2)HepG2 cells were treated with oleic acid and cholesterol to replicate the hepatocyte injury model,which was divided into NC group,Cur group,M group,and M+Cur group.Small interfering RNA for PTEN-induced kinase 1(PINK1)knockdown was used to explore the relationship between PINK1-me-diated mitophagy and NASH.Compound C(CC)was used to inhibit AMP-activated protein kinase(AMPK)to explore the effect of the AMPK/silent information regulator 1(Sirt1)pathway on mitophagy.The lipid droplets of HepG2 cells were ob-served by oil red O staining,and the levels of TC,TG,LDL-C,ALT,and AST in cell suspension were detected.RE-SULTS:(1)Compared with M group,treatment with Cur significantly reduced the body weight,liver coefficient,and se-rum levels of TC,TG,LDL-C,ALT,AST,and TNF-α in NASH mice,while the steatosis and fibrosis in the liver were improved(P<0.05).(2)Different concentrations of Cur could increase or decrease the expression of mitophagy-related proteins in HepG2 cells in a concentration gradient.Compared with the M group,Cur reduced lipid droplets and de-creased TC,TG,LDL-C,ALT,and AST levels(P<0.05).(3)Compared with the NC group,the expression levels of mi-tophagy-related proteins in the liver of mice in the M group decreased,and the expression levels of TNF-α and α-SMA pro-teins increased.Different concentrations of Cur intervention promoted the increase of mitophagy-related proteins and the decrease of TNF-α and α-SMA proteins(P<0.05).(4)After Cur intervention,the expression levels of mitophagy-related proteins increased and the expression levels of in TNF-α and α-SMA levels decreased in HepG2 cells induced by oleic acid and cholesterol(P<0.05).(5)Compared with M group,oleic-acidand cholesterol-induced mitophagy function in HepG2 cells was decreased after PINK1 knockdown(P<0.05).After CC inhibited AMPK,Cur increased the expression of p-AMPK(P<0.01),Sirt1(P<0.01),peroxisome proliferator-activated receptor γ coactivator-1α(P>0.05),PINK1(P<0.01)and parkin(P<0.01)proteins to some extent.CONCLUSION:Treatment with Cur attenuates liver injury in NASH mice and reduces lipid accumulation in HepG2 cells induced by oleic acid and cholesterol,and the mechanism may be related to promotion of mitophagy,which may involve the AMPK/Sirt1 signaling pathway.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

The application of mechanics in clinical wound healing has a long history;however,the systematic underlying mechanisms remain unclear.With recent advancements in biomechanics and mechanobiology,the principles regarding how mechanical factors influence the formation,progression,and healing of wounds have gradually been elucidated.Herein,based on progress in theories,technologies,and clinical practices concerning the interplay between mechanics and wound healing,this study introduces the concept of wound-repairing mechanomedicine.Relevant research is systematically reviewed from the perspectives of biomechanics,mechanobiology,and mechanotherapy.Additionally,potential future development directions are prospectively analyzed to provide novel insights into wound care and strategies for preventing scar formation.

Objective:To investigate the effect of early high-sucrose diet (eHSD) on cognitive function and its regulatory mechanism in 3×Tg-AD mice.Methods:(1) Eighteen specific-pathogen-free (SPF)-grade 2-month-old wide-type (WT) mice were randomly divided into a WT+normal chow diet (NCD) group and a WT+eHSD group, with 9 mice in each group; and 18 SPF-grade 2-month-old 3×Tg-AD mice were randomly divided into a 3×Tg-AD+NCD group and a 3×Tg-AD+eHSD group, with 9 mice in each group. At 2-5 months old, mice in the 4 groups received standard laboratory food+purified water or 30% sucrose water, followed by standard feed for all groups. At 8 months old, cognitive function was assessed by Morris water maze test; fluorescent intensity of AT8 (phosphorylated [p]-tau) and T22 (tau oligomers) in the hippocampal tissues was detected by immunofluorescent staining; concentrations of β-amyloid protein (Aβ) 42 and Aβ 40 were detected by enzyme-linked immunosorbent assay (ELISA); protein expressions of stimulator of interferon genes (STING), TANK-binding kinase 1 (TBK1), p-TBK1, and CCAAT/enhancer-binding protein β (C/EBPβ) were detected by Western blotting; activity of C/EBPβ transcription factor was detected by activity assay; mitochondrial DNA (mtDNA) content in the cytoplasm of cell was detected by real-time quantitative PCR (qPCR). (2) Eighteen SPF-grade 2-month-old 3×Tg-AD mice were randomized into a 3×Tg-AD+eHSD+H-151 group and a 3×Tg-AD+eHSD+dimethyl sulfoxide (DMSO) group, with 9 mice in each group. Mice at 2-5 months old were given standard laboratory food+30% sucrose water; they were, respectively, injected intraperitoneally with STING pathway inhibitor H-151 or DMSO at 5 months old, and continually injected until 8 months old; and then, the behavioral testing, immunofluorescent staining, ELISA, Western blotting and C/EBPβ transcription factor activity experiments were repeated as before. (3) After crossing C/EBPβ heterozygous knockout (C/EBPβ +/-) mice with 3×Tg-AD mice, 3×Tg-AD/C/EBPβ +/- mice were obtained, and 3×Tg-AD mice were used as controls; they were named 3×Tg-AD/C/EBPβ +/-+eHSD group and 3×Tg-AD+eHSD group, with 9 mice in each group. Both groups of mice were given standard laboratory food+30% sucrose water at 2-5 months old, followed by standard feed until 8 months old; and then, the behavioral testing, immunofluorescent staining, ELISA, and Western blotting experiments were repeated as before. (4) C/EBPβ transgenic mice (C/EBPβTg) were crossed with 3×Tg-AD mice to obtain C/EBPβTg/3×Tg-AD mice, and Non-Tg/3×Tg-AD mice were used as controls; they were, respectively, named as C/EBPβTg/3×Tg-AD+eHSD+H-151 group, Non-Tg/3×Tg-AD+eHSD+H-151 group, and Non-Tg/3×Tg-AD+eHSD+DMSO group, with 9 mice in each group. All 3 groups of mice were given standard laboratory food+30% sucrose water at 2-5 months old; at 5-8 months old, mice in the C/EBPβTg/3×Tg-AD+eHSD+H-151 group and Non-Tg/3×Tg-AD+eHSD+H-151 group were intraperitoneally injected with H-151, while mice in the Non-Tg/3×Tg-AD+eHSD+DMSO group were injected with DMSO; and then, the behavioral testing, immunofluorescent staining, ELISA, and Western blotting experiments were repeated as before. Results:(1) Compared with those in the WT+NCD group and WT+eHSD group, area under the latency curve of 3×Tg-AD+eHSD mice was significantly increased, and proportion of time spending in the targeted quadrant of mice in the 3×Tg-AD+NCD group and 3×Tg-AD+eHSD group was significantly decreased ( P<0.05); compared with that in the 3×Tg-AD+NCD group, proportion of time spending in the targeted quadrant in mice of the 3×Tg-AD+eHSD group was significantly reduced ( P<0.05). Compared with the 3×Tg-AD+NCD group, the 3×Tg-AD+eHSD group had significantly increased p-tau and tau oligomers, Aβ 42 and Aβ 40 concentrations in the hippocampus (AT8 fluorescent intensity: 1.000±0.076 vs. 2.902±0.399; T22 fluorescent intensity: 1.000±0.145 vs. 2.495±0.273; Aβ 42: 1.000±0.167 vs.1.956±0.132; Aβ 40: 1.000±0.226 vs.1.900±0.116), significantly increased C/EBPβ protein expression and C/EBPβ transcription factor activity (1.000±0.164 vs. 1.804±0.112; 1.000±0.216 vs. 2.743±0.301), and statistically increased mtDNA level detected by D-loop1 and D-loop3 (1.000±0.234 vs. 2.800±0.210; 1.000±0.155 vs. 2.952±0.078; P<0.05). Compared with the 3×Tg-AD+NCD group, the 3×Tg-AD+eHSD group had significantly increased STING protein expression and p-TBK1/TBK1 ratio (STING: 1.000±0.192 vs. 2.093±0.081; p-TBK1/TBK1: 1.000±0.148 vs. 1.561±0.112, P<0.05). (2) Compared with the 3×Tg-AD+eHSD+DMSO group, the 3×Tg-AD+eHSD+H-151 group had significantly decreased area under the latency curve, significantly increased proportion of time spending in the targeted quadrant, significantly decreased p-tau and tau oligomers expressions, Aβ 42 and Aβ 40 concentrations in the hippocampus (AT8 fluorescent intensity: 1.000±0.142 vs. 0.538±0.057; T22 fluorescent intensity: 1.000±0.104 vs. 0.665±0.088; Aβ 42: 1.000±0.084 vs. 0.600±0.007; Aβ 40: 1.000±0.138 vs. 0.476±0.083), significantly decreased STING protein expression and p-TBK1/TBK1 ratio (STING: 1.000±0.054 vs. 0.468±0.111; p-TBK1/TBK1: 1.000±0.057 vs. 0.598±0.090), and significantly decreased C/EBPβ transcription factor activity (1.000±0.097 vs. 0.445±0.106; P<0.05). (3) Compared with the 3×Tg-AD+eHSD group, the 3×Tg-AD/C/EBPβ +/-+eHSD group had significantly decreased area under the latency curve, significantly increased proportion of time spending in the targeted quadrant, significantly decreased p-tau and tau oligomers, Aβ 42 and Aβ 40 concentrations in the hippocampus (AT8 fluorescent intensity: 1.000±0.160 vs. 0.506±0.065; T22 fluorescent intensity: 1.000±0.127 vs. 0.346±0.048; Aβ 42: 1.000±0.017 vs. 0.510±0.101; Aβ 40: 1.000±0.098 vs. 0.586±0.153), and significantly decreased C/EBPβ protein expression (1.000±0.101 vs. 0.568±0.094; P<0.05). (4) Compared with the Non-Tg/3×Tg-AD+eHSD+DMSO group, the Non-Tg/3×Tg-AD+eHSD+H-151 group had significantly decreased area under the latency curve, significantly increased proportion of time spending in the targeted quadrant, and significantly decreased p-tau and tau oligomers expressions, Aβ 40 concentration in the hippocampus, and the Non-Tg/3×Tg-AD+eHSD+H-151 group, the C/EBPβTg/3×Tg-AD+eHSD+H-151 group had significantly decreased STING protein expression and p-TBK1/TBK1 ratio in the hippocampus ( P<0.05). Compared with the Non-Tg/3×Tg-AD+eHSD+H-151 group, the C/EBPβTg/3×Tg-AD+eHSD+H-151 group had significantly increased area under the latency curve, significantly decreased proportion of time spending in the targeted quadrant, and significantly increased p-tau and tau oligomers expressions, Aβ 40 and Aβ 42 concentration in the hippocampus ( P<0.05). Conclusion:The eHSD aggravates cognitive impairment in 3×Tg-AD mice through activating cGAS-STING-C/EBPβ pathway.

BACKGROUND:Anybody musculoskeletal modeling system uses mathematical modeling techniques to simulate the relationship between human bones,muscles,and the environment,allowing for the study of inverse dynamics of the human body and obtaining indicators such as lower limb joint forces.OBJECTIVE:To analyze the stress distribution patterns of lower limb joints during the practice of Tai Chi movements,thereby exploring the scientific training and exercise value of Tai Chi.METHODS:Eight Tai Chi master-level athletes were selected from the Wushu College of Beijing Sport University for data collection,including seven sets of stepping movements and CT scans of the right femur.The BTS infrared capture system and Kistler three-dimensional force platform were used to collect kinematic and mechanical data of the seven sets of stepping movements in Tai Chi(Eight Methods and Five Steps).The Anybody 7.2 musculoskeletal model's multi-body dynamics simulation technology was utilized to calculate lower limb joint dynamic parameters,and Workbench 19.2 was used to perform stress analysis on the femur.RESULTS AND CONCLUSION:(1)Using Workbench software,the stress results of the femur for seven sets of movements were obtained.The peak stress values of the seven sets of movements in descending order were:Retreat and Rollback(22.00 MPa),Retreat and Pluck(19.379 MPa),Left and Right Shift Step Squeeze and Press(9.35 MPa),Left and Right Shift Step Elbow Lean(6.30 MPa),Forward Step and Expand(4.68 MPa),Forward Step and Pull(2.57 MPa),and Middle Fixed Standalone Position(0.31 MPa).(2)In the seven sets of stepping movements,the two backward stepping movements resulted in the greatest stress on the femur(P＜0.05),and the maximum stress positions on the femur were different during the movement of the seven sets of actions.(3)It is concluded that during the seven sets of stepping movements in Tai Chi(Eight Methods and Five Steps),stress threshold and maximum stress position of the femur will vary with different movements in five directions(seven sets of movements).Continuous training can comprehensively stimulate the femoral body.Forward stepping movements have a greater impact on the front and upper lateral side of the femoral body,while backward stepping movements have a greater impact on the back and inner side of the femoral body.Left and right lateral stepping movements mainly involve symmetrical stress on both sides of the femoral body.(4)Beginners should train targeted according to the stress characteristics of different stepping movements.During forward and backward stepping movements,attention should be paid to the rotational force of Tai Chi,and during left and right lateral stepping movements,attention should be paid to the medial counterforce.Beginners should focus on the Tai Chi training steps that correspond to their own weaknesses to achieve better exercise outcomes.