BACKGROUND:Bone defects can directly affect the success rate and long-term stability of dental implants.Studies have shown that salidroside has the ability to promote the proliferation and differentiation of osteoblasts,but less is reported on its pathways related to osteogenic differentiation. OBJECTIVE:To investigate the effects of salidroside on the proliferation and differentiation of MC3T3-E1 cells and the expression of related genes and proteins through in vitro cell experiments. METHODS:Cell counting kit-8 test and alkaline phosphatase test were used to determine the optimal concentration of salidroside(0.5,1,5,10,and 50 μmol/L)in promoting the proliferation and differentiation of MC3T3-E1 cells.There were four groups in the experiment:control group,salidroside group,salidroside+LY294002 group,and LY294002 group,which were cultured with osteogenic induction solution,osteogenic induction solution containing 10 μmol/L salidroside,osteogenic induction solution containing 10 μmol/L salidroside+10 μmol/L LY294002,and osteogenic induction solution containing 10 μmol/L LY294002,respectively.The effects of salidroside and LY294002,an inhibitor of the PI3K/Akt signaling pathway,on the expressions of genes and proteins related to osteogenesis were observed. RESULTS AND CONCLUSION:Cell counting kit-8 assay and alkaline phosphatase assay showed that salidroside promoted the proliferation of MC3T3-E1 cells most significantly at 10 μmol/L.Compared with the control group,salidroside could promote mineralization,promote cell adhesion,reduce cell death,increase mRNA expression of Runx-2,osteocalcin and osteopontin(P<0.01),and increase protein expression of Runx-2 and p-Akt(P<0.01).However,the addition of LY294002 reversed the above results.These findings indicate that salidroside can promote the mineralization of MC3T3-E1 cells and the expression of osteogenesis-related genes and proteins,which may be related to the activation of PI3K/Akt signaling pathway.

BACKGROUND:Several observational studies have found a close relationship between thyroid function levels and sarcopenia,but the causal relationship between thyroid function levels and the onset of sarcopenia is not yet clear. OBJECTIVE:To investigate the causal relationship between thyroid function levels and sarcopenia using a two sample Mendelian randomization method. METHODS:A two sample Mendelian randomization analysis was conducted using genome-wide association study data on thyrotropin,free triiodothyronine,free tetraiodothyronine,subclinical hyperthyroidism,subclinical hypothyroidism,and four related phenotypes of sarcopenia-lefthand grip strength,right hand grip strength,limb lean mass,and gait speed.The inverse-variance weighted method,weighted median method,simple mode method,weighted median estimator method,and MR Egger regression method were used as analysis methods,while heterogeneity test,pleiotropy test,MR-PRESSO,leave-one-out method,funnel plot and other methods were used for sensitivity analysis. RESULTS AND CONCLUSION:Elevated levels of thyroid-stimulating hormone increased left-(β=0.02,SE=0.01,P=0.01)and right-handed grip strength(β=0.02,SE=0.01,P=0.01),an increase in free triiodothyronine decreased left-(β=-0.06,SE=0.02,P=9.5×10-5)and right-handed grip strength(β=-0.07,SE=0.02,P=9.3×10-5),and subclinical hyperthyroidism decreased gait speed(β=-4.4×10-3,SE=1.7×10-3,P=0.01).The sensitivity analysis results were basically consistent with the main analysis results.To conclude,an increase in thyroid-stimulating hormone is a protective factor for sarcopenia,and elevation of free triiodothyronine and subclinical hyperthyroidism may increase the risk of sarcopenia.

As the important source of bone cells, osteoblasts are involved in bone formation and repair, and play a key role in maintaining bone balance. If the osteogenic differentiation process in vivo is disrupted, a variety of bone-related diseases may occur. Natural products, which have a wide range of sources, a wide variety of physiological activities, and few toxic side-effects, have been found in recent years to be able to regulate osteoblast differentiation. Based on the sources of natural products, this paper reviews the intervention of natural products from plant, animal and microbial sources on osteogenic differentiation, aiming to provide a theoretical basis for natural products in the treatment of bone diseases.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Carbamate pesticides, a new type of broad-spectrum pesticides for controlling pests, mites, and weeds, are developed to address the shortcomings of organochlorine and organophosphorus pesticides. Their widespread use and slow degradation have led to environmental pollution, causing damage to ecosystems and human health. Managing pesticide residues is a pressing issue in the current environmental protection. This study aims to investigate the expression of SyEst870, a member of the SGNH/GDSL hydrolase family in Sphingobium yanoikuyae, in a prokaryotic system and evaluate the ability of the recombinant protein to degrade carbamate pesticides. The prokaryotic expression vector pET-32a-SyEst870 was constructed and transformed into the Escherichia coli BL21 for heterologous expression. The purified protein was studied in terms of enzyme activity and effects of temperature, pH, and metal ions on the enzyme activity, with p-nitrophenol acetate as the substrate and based on the standard curve of p-nitrophenol. LC-MS (liquid chromatography-mass spectrometry) was employed to examine the degradation effects of SyEst870 on carbaryl, metolcarb, and isoprocarb. GC-MS (gas chromatography-mass spectrometry) was employed to detect the degradation products of SyEst870 for the three pesticides. The soluble protein SyEst870 was successfully obtained through the heterologous expression in Escherichia coli, which yielded an enzyme with the activity of 677.5 U after affinity chromatography. SyEst870 exhibited degradation rates of 82.34%, 84.43%, and 92.87% for carbaryl, metolcarb, and isoprocarb, respectively, at an initial concentration of 100 mg/L within 24 h at 30 ℃ and pH 7.0. The primary degradation products of carbaryl were identified as α-naphthol and methyl isocyanate. Metolcarb was mainly degraded into m-cresol and methyl isocyanate, and isoprocarb was mainly degraded into 2-isopropylphenol and methyl isocyanate. Compared with the half-life of carbamate pesticides in the natural environment, which ranges from a few days to several weeks, the recombinant protein SyEst870 can rapidly eliminate the residues of carbamate pesticides. This study lays a foundation for addressing pesticide residues in the environment and in fruits and vegetables.
Escherichia coli/metabolism* ; Sphingomonadaceae/genetics* ; Recombinant Proteins/metabolism* ; Biodegradation, Environmental ; Esterases/metabolism* ; Pesticides/isolation & purification* ; Carbamates/isolation & purification*

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
Humans ; Ischemic Stroke ; Brain/metabolism* ; Macrophages ; Brain Ischemia/metabolism* ; Microglia/metabolism* ; Gene Expression Profiling ; Anti-Inflammatory Agents ; Neuronal Plasticity/physiology* ; Infarction/metabolism*

Background The mental health status of prison officers is crucial to the efficiency, security, and stability of a prison, and it is essential to pay attention to the factors that influence their mental health. Objective To understand the mental health status of prison officers, and analyze how nature exposure affects their mental health problems and a potential mediating role of mental fatigue. Methods A cross-sectional survey was carried out from May to June 2022 among 1392 prison officers from eight prisons in a province, and a total of 1284 valid questionnaires were recovered. The Nature Exposure Scale, Mental Fatigue Scale, and Depression-Anxiety-Stress Scale were used to assess nature exposure, mental fatigue, and mental health indicators among prison officers, and to explore the effect of nature exposure on mental health problems and a potential mediating role of mental fatigue. Results The recruited prison officers showed high levels of depression, anxiety, and stress. The prevalence rates of depression, anxiety, and stress were 59.11% (759/1284), 60.67% (779/1284),and 43.93% (564/1284), respectively. The results of correlation analysis revealed that nature exposure was negatively related with mental fatigue and mental health indicators (depression, anxiety, and stress) (r_s=−0.242, −0.308, −0.235, −0.254, P<0.01), while mental fatigue was positively correlated with mental health indicators (depression, anxiety, and stress) (r_s=0.546, 0.533, 0.536, P<0.01). The PROCESS macro results showed that the level of nature exposure among prison officers negatively associated with depression, anxiety, and stress (β=−0.180, −0.104, −0.123), and mental fatigue played a mediating role, with indirect effects of −0.200, −0.192, and −0.199, respectively. Conclusion The levels of depression, anxiety, and stress of prison officers are higher than those of other occupations. Nature exposure negatively associates with depression, anxiety, and stress, that is, it may directly alleviate the mental health problems of prison officers; and it may also alleviate mental health problems by relieving mental fatigue.

Objective To observe the effect of Shenfu injection on lung injury caused by hemor-rhagic shock(HS)in rats and explore the related potential mechanism.Methods Thirty-six SPF healthy male SD rats,aged 16-17 weeks,weighing 400-600 g,were randomly divided into three groups:sham op-eration group(group SH),HS group(group HS),and Shenfu injection group(group SF),12 rats in each group.In group SH,only the right femoral vein and femoral artery were separated after anesthesia,and ve-nous catheterization was not performed.HS model was established in groups SF and HS.In group HS,liquid resuscitation was performed through an intravenous catheter,and the resuscitation fluid consisted of the auto-blood lost and the compound sodium chloride injection equivalent to 1.5 times the blood loss and 10 ml/kg normal saline.In group SF,the resuscitation fluid consisted of the lost autoblood and the compound sodium chloride injection equivalent to 1.5 times the blood loss and Shenfu injection 10 ml/kg.The whole perfusion time was about 60 minutes.Six rats in the three groups were randomly anesthetized 24 and 48 hours after op-eration.The wet/dry weight ratio(W/D)of lung tissues was detected.The concentrations of interleukin-6(IL-6),IL-17,IL-10,and transforming growth factor-β(TGF-β)were detected by ELISA,the mRNA ex-pression of retinoic acid-related orphan nuclear receptor γt(RORγt),transcription factor forkhead box pro-tein 3(Foxp3),and hypoxia-inducible factor-1α(HIF-1α)in lung tissues were detected by PCR.The pro-tein contents of RORγt,Foxp3,HIF-1α,aquaporin 1(AQP1),and AQP5 in lung tissue were detected by Western blot.Pathological changesunder HE staining light microscope and lung injury scores were observed.Results Compared with 24 hours after operation,W/D,the concentrations of IL-6 and IL-17,mRNA ex-pression and protein content of RORγt and HIF-1α,and lung injury score were significantly decreased(P＜0.05),the concentrations of IL-10,and TGF-β,Foxp3 mRNA expression and protein content,and AQP1 protein content were significantly increased in group SF 48 hours after operation(P＜0.05).Compared with group SH,W/D,the concentrations of IL-6,IL-17,IL-10,and TGF-β,mRNA expression and protein content of RORγt,Foxp 3,and HIF-1α,and lung injury score were significantly increased(P＜0.05),AQP1 and AQP5 protein contents were significantly decreased in groups HS and SF 24 and 48 hours after operation(P＜0.05),and alveolar structure was damaged under light microscope and alveolar interstitium was filled with a large amount of edematous fluid,during which a large number of inflammatory cells infiltra-ted.Compared with group HS,W/D,the concentrations of IL-6 and IL-17,mRNA expression and protein content of RORγt and HIF-1α,and lung injury score were significantly decreased(P＜0.05),the concen-trations of IL-10 and TGF-β,Foxp3 mRNA expression and protein content,AQP1 and AQP5 protein con-tents were significantly increased in group SF 24 and 48 hours after surgery(P＜0.05),and the alveolar structure was improved under light microscope,and edema was reduced,and the number of inflammatory cells was reduced.Conclusion Shenfu injection can regulate the balance between pro-inflammatory factors IL-6 and IL-17,and anti-inflammatory factors IL-10 and TGF-β,increase the protein content of AQP1 and AQP5 in lung tissue,and decrease the W/D and injury score in lung tissue,thus alleviating lung injury in HS rats.The mechanism may be related to the regulation of HIF-1α-RORγt/Foxp3 balance.

ObjectiveTo investigate the factors related to the abandonment of upper limb prostheses. MethodsA total of 138 amputees fitting with upper limb prostheses at Guangdong Work Injury Rehabilitation Hospital from January 1st, 2016 to December 31st, 2022 were reviewed through case data, and those whose Functional Independence Measure scores improved after fitting were selected. A total of 126 amputees were investigated through telephone or WeChat with a questionnaire. The questionnaire was designed based on Trinity Amputation and Prosthesis Experience Scale-Revised, short form of Health Survey (SF-36) and World Health Organization Quality of Life Scale-Brief, and the items that may lead to the abandonment of upper limb prostheses were summarized in four factors: amputee, prosthetic fitting, prosthetic training, and environment and social policy. ResultsThe overall abandonment rate was 23.0% (29/126). There was significant difference between the the amputee abandonment or using prostheses in educational levels, amputation levels and residual limb condition (χ² > 6.808, P < 0.05); types of prostheses, whether functional prostheses, expectation for prosthesis, comfort of the prostheses, convenience of putting on and taking off, sensitivity of manipulation, weight of the prostheses, satisfaction with the appearance, skill levels of the prosthetist, the satisfaction after prosthesis installation and satisfaction with the prostheses in use (χ² > 13.083, P < 0.05); training levels before prosthesis assembly, the mastery of functional prostheses three months after prosthesis installation, training for activities of daily living, simulated training for vocation (χ² > 6.520, P < 0.05); willingness to participate in social activities with prostheses, attitude of other persons towards their prostheses, support of family members, work status, familiarity with the policies of welfare, and the current physical condition (χ² > 13.152, P < 0.01). ConclusionFactors of amputee, prosthetic fitting, prosthetic training, and environment and social policy may relate to the abandonment of upper limb prostheses, which are needed to improve in an accurate way.

OBJECTIVE To explore the mechanism of Compound lizard powder reducing cisplatin resistance in gastric cancer by regulating glycolytic activity based on phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt） signaling pathway. METHODS Human gastric cancer MKN45 and MKN45/DDP （cisplatin-resistant） cells were cultured in vitro and intervened with different mass concentrations of cisplatin （0.1， 0.2， 0.4， 0.8， 1.6， 3.2 μg/mL） to detect the survival rate， half inhibitory concentration （IC50） and drug resistance index. MKN45/DDP cells were inoculated subcutaneously in the right anterior axilla of nude mice to prepare a transplanted tumor model of gastric cancer. After successful modeling， they were randomly divided into model group， cisplatin group （0.002 g/kg）， Compound lizard powder group （2.8 g/kg） and combination group （the same dose as each single drug group）， with 8 nude mice in each group. Each administration group was given relevant solution， twice a week （cisplatin， i.p.） or twice a day （Compound lizard powder， i. g.）， for 4 consecutive weeks. During the experiment， the body weight of nude mice was monitored， and tumor volume and inhibitory rate of tumor were calculated. The levels of inflammatory factors （tumor necrosis factor- α， interleukin-6） in tumor tissue， the mRNA and protein expressions of multidrug resistance-associated protein 1 （MRP1）， P-glycoprotein （P-gp）， glucose transporter-1 （GLUT1） and lactate dehydrogenase A （LDHA）， as well as the protein expressions of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， hexokinase-2 （HK2） and pyruvate kinase M2 （PKM2） were all detected. RESULTS With the intervention of different concentrations of cisplatin， the survival rate of MKN45/DDP-resistant cells was significantly higher than that of MKN45 parent cells （P＜0.05）. IC50 value of MKN45/DDP and MKN45 cells were（1.052 0±0.221 9） and （0.372 1±0.238 0）μg/mL， and the drug resistant index was 2.827. Compared with the model group， cisplatin group， Compound lizard powder group and combination group all had certain inhibitory effects on the tumor growth in nude mice； the inhibitory rates of tumor increased significantly （P＜0.05）； the levels of inflammatory factors， the mRNA and protein expressions of MRP1， P-gp， GLUT1 and LDHA （except for cisplatin group）， the phosphorylation levels of PI3K and Akt protein （except for cisplatin group） as well as the protein expressions of HK2 and PKM2 were decreased significantly， while the combination group was significantly better than the cisplatin group （P＜0.05）. CONCLUSIONS Compound lizard powder may inhibit tumor growth in transplanted tumor model nude mice with gastric cancer-resistant cells by reducing the secretion of tumor-related inflammatory factors， inhibiting the expression of glycolysis， drug resistance-related proteins and genes， inhibiting the activation of the PI3K/Akt signaling pathway， thus having a certain effect of enhancing cisplatin efficacy and reversing drug resistance.