ObjectiveTo investigate differential metabolites associated with browning in the post-harvest processing of Pinelliae Rhizoma， providing data support for elucidating the key metabolites and metabolic pathways involved in browning， and developing safe and efficient sulfur-free processing techniques. MethodsUltra-performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry（UPLC-QTRAP-MS/MS） was used to detect the metabolites of Pinelliae Rhizoma at different browning stages（0， 8， 16 h） for widely targeted metabolomics. Subsequently， Multivariate statistical analysis of metabolites was conducted using principal component analysis（PCA）， hierarchical cluster analysis（HCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA）， and K-means cluster analysis. Differential metabolites at different browning stages were screened based on variable importance in the projection（VIP） value>1 and |log₂fold change（FC）|≥1， and metabolic pathway enrichment analysis was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultsA total of 1 416 metabolites were identified across the three browning stages of Pinelliae Rhizoma， predominantly comprising amino acids and their derivatives（239）， lipids（219）， alkaloids（156）， phenolic acids（121）， terpenoids（113）， and flavonoids（111）. A two-by-two comparison of the three browning phases， yielded 622 differential metabolites that were significantly enriched in the phenylpropanoid biosynthesis， flavone and flavonol biosynthesis， and purine metabolic pathway. Further analysis revealed that carbohydrates such as D-mannose and turanose， phenolic acids such as 1-O-caffeoyl-6-O-glucosyl-β-D-glucose， dicaffeoylshikimic acid， and flavonoids such as epigallocatechin gallate， vitexin-7-O-rutinoside， luteolin-7-O-（6″-malonyl）glucoside-5-O-arabinoside， catechin gallate， epicatechin gallate， isovitexin-7-O-glucoside-2″-O-rhamnoside， apigenin-7-O-rutinoside-4ʹ-O-sophoroside， 3，5，3ʹ，4ʹ，5ʹ-penta-hydroxyflavan-7-gallate may act as browning substrates and play important roles in the browning process. ConclusionCarbohydrates， phenolic acids， and flavonoids may serve as key substrates in the browning process of Pinelliae Rhizoma， involving pathways such as phenylpropanoid biosynthesis， flavone and flavonol biosynthesis， and purine metabolism， which can provide a theoretical basis for further exploration of the browning mechanism.

Objective To observe the effects of electroacupuncture(EA)on TGF-β1/Smads signaling pathway and epithelial-mesenchymal transition(EMT)related proteins in rats with neurogenic bladder(NB)after spinal cord injury;To explore the possible mechanism of EA in improving NB fibrosis.Methods Totally 36 female SD rats were randomly selected,with 10 rats in the sham-operation group and the remaining 26 rats undergoing complete transection of the spinal cord beneath the T8 vertebrae to establish a NB rat model.The modeling rats were randomly divided into model group and EA group,with 10 rats in each group.EA group was applied to"Ciliao","Zhongji"and"Sanyinjiao",20 min per time,once a day for 7 days.The general condition of the rats in each group was observed,the ultrasound index of the bladder was detected by ultrasound technique,the bladder function of the rats was detected by urodynamics,the body mass of the rats and the wet weight of the bladder were recorded,and the bladder index was calculated.HE staining was used to observe bladder tissue morphology,the degree of bladder tissue fibrosis and bladder wall thickness were detected by Masson staining.The positive expressions of E-cadherin,N-cadherin and Vimentin in bladder tissue were detected by immunohistochemistry.The protein expressions of TGF-β1,p-Smad2/3,E-cadherin,N-cadherin and Vimentin were detected by Western blot.Results Compared with the sham-operation group,the upper and lower diameter,anteroposterior diameter,transverse diameter,bladder volume of the model group significantly increased(P<0.001),the maximum bladder pressure,leak point pressure difference,perfusion time and maximum bladder capacity significantly increased(P<0.001),the bladder index increased significantly(P<0.001),the bladder epithelial cells were thickened and arranged irregularly,the bladder collagen volume fraction and bladder wall thickness significantly increased(P<0.001),the expressions of TGF-β1,p-Smad2/3,N-cadherin and Vimentin in bladder tissue increased(P<0.01),and the expression of E-cadherin decreased(P<0.001).Compared with the model group,the upper and lower diameter,anteroposterior diameter,transverse diameter,bladder volume of the EA group decreased significantly(P<0.05),the maximum bladder pressure,leak point pressure difference,perfusion time and maximum bladder capacity significantly decreased(P<0.05),the bladder index significantly decreased(P<0.05),the thickness of the bladder epithelial cell layer became thinner and arranged more neatly,and the bladder collagen volume fraction and bladder wall thickness of the bladder were significantly reduced(P<0.05),the expressions of TGF-β1,p-Smad2/3,N-cadherin and Vimentin in bladder tissue significantly decreased(P<0.05),and the expression of E-cadherin significantly increased(P<0.05).Conclusion EA may reduce the EMT of bladder epithelial cells and decrease the degree of bladder tissue fibrosis by inhibiting the activation of the TGF-β1/Smads signaling pathway,thereby improving bladder function in NB rats after spinal cord injury.

Objective:To observe the effect of moxibustion on angiogenesis-related indicators in knee joint synovial tissue of adjuvant arthritis model rats,and to explore the mechanism of moxibustion in inhibiting vascular endothelial growth factor(VEGF)expression in synovial tissue and further limiting the activation of Rho family proteins Rac1 and Cdc42,thereby inhibiting angiogenesis during rheumatoid arthritis(RA)treatment.Methods:Forty-eight male Sprague-Dawley rats were equally divided into a normal group,a model group,a moxibustion group,and a moxibustion+VEGF agonist group according to the random principle.The complete Freund's adjuvant method was used for modeling.On the 12th day after modeling,the moxibustion group and the moxibustion+VEGF agonist group were subjected to suspended moxibustion at bilateral Zusanli(ST36),Guanyuan(CV4),and Ashi points for 20 min each time,once a day,for a total of 15 times.The moxibustion+VEGF agonist group received VEGF agonist(tirofiban hydrochloride hydrate)injection in the knee joint cavity at the same time.Hematoxylin-eosin staining was used to evaluate the pathological changes of rat synovial tissue in each group.Immunohistochemistry was used to observe the CD31 expression level in rat synovial tissue.Western blotting was used to detect the levels of VEGF,Rac1,and Cdc42 protein in rat synovial tissue,and polymerase chain reaction(PCR)was used to detect the VEGF mRNA expression.Results:Compared to the normal group,the expression levels of CD31 protein and VEGF mRNA and protein in rat synovial tissue in the model group increased significantly(P<0.01),and the expression levels of phospho-Rac1 and phospho-Cdc42 proteins also increased significantly(P<0.01).After moxibustion intervention,the expression levels of CD31 protein and VEGF mRNA and protein in the moxibustion group were significantly lower than those in the model group(P<0.01),while the differences in each indicator between the moxibustion+VEGF agonist group and the model group were not statistically significant(P>0.05).Compared to the moxibustion group,the expression levels of CD31 protein,VEGF mRNA and protein,phospho-Cdc42,and phospho-Rac1 in the moxibustion+VEGF agonist group increased significantly(P<0.01).Conclusion:Moxibustion improved synovial inflammation in RA by inhibiting angiogenesis.The mechanism may be to regulate angiogenesis-related VEGF,restrict the activation of Rac1 and Cdc42,and inhibit pseudopodia formation in vascular endothelial cells,thereby reducing angiogenesis.

The blue fluorescent carbon dots(TMCDs)and cyan fluorescent carbon dots(TMCDs-H2O)were synthesized fromm-phenylenediamine and tricarballylic acid through air-assisted melting polymerization and one-step hydrothermal method,respectively.Air purging could effectively inhibit the side reactions and reduce the derivative structures in the carbon dots product.The structure and morphology of these two materials were systematically characterized using liquid nuclear magnetic resonance spectroscopy(NMR),mass spectrometry(MS),and transmission electron microscopy.Compared to TMCDs-H2O((3.12±0.63)nm),TMCDs showed a smaller average particle size(approximately(1.85±0.02)nm).The NMR and MS analysis revealed that although the main structure of both types of carbon dots was similar,TMCDs exhibited a simpler structure with higher degree of polymerization.These results suggested that supramolecular interactions might introduce numerous small molecule derivatives into TMCDs-H2O particles,resulting in lower polymerization degree,multiple substructures,and larger particle size characteristics for this material.When employed as chemical sensors for metal ion detection,in the linear range of 1×10-5-5×10-4 mol/L,the detection limits of Fe3+by TMCDs and TMCDs-H2O were 3.3×10-6 mol/L and 3.8×10-6 mol/L,respectively.The experimental results demonstrated that the recoveries of CDs and inductively coupled plasma optical emission spectrometer(ICP-OES)were similarity,whereas TMCDs displayed a considerable relative standard deviation.This study demonstrated that endogenously derived structures in CDs could enhance the performance of metal ion sensing.

Lentiviral vectors(LVs)are key gene delivery tools for integrating target genes into the host genome,but they may also pose risks of insertional mutagenesis.The vector copy number(VCN)in cells is critical for determining the safety of gene modification.However,the reliability and accuracy of its quantification process are influenced by multiple factors.Developing cell reference materials with specific vector copy numbers represents a viable approach to enhance the reliability and consistency of measurement results,enabling quality control of the quantification process and traceability of outcomes.However,the preparation of such reference materials faces challenges in cell sample design,preparation protocols,and advanced quantification techniques.In this study,T lymphocyte cell line Jurkat-based reference materials with LV gene copy numbers of 1 and 2 copy/cell were developed.A high-precision duplex digital polymerase chain reaction(dPCR)method was established to quantify the LV gene and endogenous genes simultaneously.Additionally,the results of dPCR were cross-validated through next-generation sequencing and flow cytometric analysis.Ultimately,confocal microscopy characterization results showed that the developed cell reference materials had intact morphology.The quantification result of VCN-1 was(1.07±0.11)copy/cell,and that of VCN-2 was(2.09±0.21)copy/cell.These cell reference materials demonstrated compliance with stability and homogeneity requirements,and could be applied for quality control throughout the VCN measurement workflow and metrological traceability,improving the accuracy,comparability,and validity of copy number measurements.

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

The rise of nanomedicine has opened up new avenues for drug delivery and tumor treatment.Nanocarriers,in particular,have become core tools in the field of drug delivery.Anti-cancer peptides(ACPs)can achieve anti-tumor effects by inducing tumor cell apoptosis,inhibiting angiogenesis,and regulating the immune microenvironment.Their low toxic side effects and drug resistance make them im-portant in the field of cancer treatment.However,ACPs face limitations such as poor stability,short in vivo half-life,and low targeted delivery efficiency,which seriously limit their therapeutic effects and fur-ther development.Nanocarriers provide an efficient,flexible and precise solution for the delivery of ACPs due to their advantages of increasing drug solubility,changing drug distribution in the body and improving drug targeting.This review systematically summarizes the structural characteristics and biological proper-ties of four types of nanocarriers,including liposome nanocarriers,polymer nanocarriers,inorganic nano-carriers,and self-assembled peptides,and focuses on analyzing the application examples of nanocarriers in enhancing the stability of ACPs,improving targeted delivery efficiency,improving bioavailability,and overcoming drug-resistant tumor treatment.We also summarize in detail the structural pros and cons of these four carriers.Finally,we look forward to the development direction of research on the combination of nanocarriers and ACPs,in order to provide a theoretical basis for the clinical application of ACPs.

Objective To observe the effects of electroacupuncture(EA)on TGF-β1/Smads signaling pathway and epithelial-mesenchymal transition(EMT)related proteins in rats with neurogenic bladder(NB)after spinal cord injury;To explore the possible mechanism of EA in improving NB fibrosis.Methods Totally 36 female SD rats were randomly selected,with 10 rats in the sham-operation group and the remaining 26 rats undergoing complete transection of the spinal cord beneath the T8 vertebrae to establish a NB rat model.The modeling rats were randomly divided into model group and EA group,with 10 rats in each group.EA group was applied to"Ciliao","Zhongji"and"Sanyinjiao",20 min per time,once a day for 7 days.The general condition of the rats in each group was observed,the ultrasound index of the bladder was detected by ultrasound technique,the bladder function of the rats was detected by urodynamics,the body mass of the rats and the wet weight of the bladder were recorded,and the bladder index was calculated.HE staining was used to observe bladder tissue morphology,the degree of bladder tissue fibrosis and bladder wall thickness were detected by Masson staining.The positive expressions of E-cadherin,N-cadherin and Vimentin in bladder tissue were detected by immunohistochemistry.The protein expressions of TGF-β1,p-Smad2/3,E-cadherin,N-cadherin and Vimentin were detected by Western blot.Results Compared with the sham-operation group,the upper and lower diameter,anteroposterior diameter,transverse diameter,bladder volume of the model group significantly increased(P<0.001),the maximum bladder pressure,leak point pressure difference,perfusion time and maximum bladder capacity significantly increased(P<0.001),the bladder index increased significantly(P<0.001),the bladder epithelial cells were thickened and arranged irregularly,the bladder collagen volume fraction and bladder wall thickness significantly increased(P<0.001),the expressions of TGF-β1,p-Smad2/3,N-cadherin and Vimentin in bladder tissue increased(P<0.01),and the expression of E-cadherin decreased(P<0.001).Compared with the model group,the upper and lower diameter,anteroposterior diameter,transverse diameter,bladder volume of the EA group decreased significantly(P<0.05),the maximum bladder pressure,leak point pressure difference,perfusion time and maximum bladder capacity significantly decreased(P<0.05),the bladder index significantly decreased(P<0.05),the thickness of the bladder epithelial cell layer became thinner and arranged more neatly,and the bladder collagen volume fraction and bladder wall thickness of the bladder were significantly reduced(P<0.05),the expressions of TGF-β1,p-Smad2/3,N-cadherin and Vimentin in bladder tissue significantly decreased(P<0.05),and the expression of E-cadherin significantly increased(P<0.05).Conclusion EA may reduce the EMT of bladder epithelial cells and decrease the degree of bladder tissue fibrosis by inhibiting the activation of the TGF-β1/Smads signaling pathway,thereby improving bladder function in NB rats after spinal cord injury.

Objective:To observe the effects of electroacupuncture(EA)on learning and memory ability and nucle-ar factor E2 related factor 2(Nrf2),glutathione peroxidase 4(GPX4),NAD(P)H-quinone oxidoreductase 1(NQO1),reactive oxygen species(ROS)in hippocampus of neonatal rats with hypoxic-ischemic brain damage(HIBI)and its anti-oxidative stress mechanism.Methods:A total of 76 neonatal rats were randomly divided into Sham opera-tion group(Sham),HIBI model group(HIBI),electroacupuncture group(HIBI+EA),and Nrf2 inhibitor ML385 group(HIBI+EA+ML385).The neonatal rat model of HIBI was established by classical Rice method.The HIBI+EA group was treated with electroacupuncture for 30 min/d for 14 consecutive days.In the HIBI+EA+ML385 group,30 mg/kg ML385 was intraperitoneally injected at 1 h before each electroacupuncture intervention.Morris water maze test was performed on 21 days after modeling to test the learning and memory ability of neonatal rats in each group.Nissl staining and HE staining were used to observe the morphology of neurons in the hippocampal CA1 region,and DHE flu-orescent probe was used to detect the expression of ROS in the hippocampal CA1 region.The contents of Nrf2,GPX4 and NQO1 in hippocampus were detected by Western blot.Results:Compared with the Sham group,the HIBI group had severe pathological damage,a prolonged escape latency,a decreased number of platform crossings,a significantly increased expression of ROS,and a significantly decreased expression of Nrf2,GPX4,and NQO1(P<0.05).Com-pared with HIBI group,the pathological damage was significantly attenuated,the escape latency was shortened,the number of platform crossings was increased,the expression of ROS was decreased,and the expression of Nrf2,GPX4 and NQO1 was increased in HIBI+EA group(P<0.05).Compared with HIBI+EA group,the pathological damage was aggravated,the escape latency was prolonged,the number of crossing the platform was decreased,the expression of ROS was increased,and the expression of Nrf2,GPX4,and NQO1 was decreased in HIBI+EA+ML385 group(P<0.05).Conclusion:Electroacupuncture can effectively improve the learning and memory ability of hypoxic-ischemic neonatal rats,which is related to its effect in reducing oxidative stress in hippocampal neurons by regulating Nrf2 signa-ling pathway.