Epigallocatechin gallate (EGCG), the most abundant catechin in green tea, possesses various biomedical activities and has garnered significant attention because of its notable anticancer properties. This article reviews the research progress on the antitumor mechanisms of EGCG, focusing on its roles in inducing tumor cell apoptosis; inhibiting tumor cell proliferation, angiogenesis, invasion and metastasis; modulating the tumor microenvironment; and influencing epigenetic modifications. Given its natural origin, safety, and low cost, EGCG could be a preferred option for the development of new cancer therapeutic drugs or enhancing the efficacy of combination therapies. This work aims to provide a theoretical foundation for further research and development of EGCG and scientific evidence for its application in cancer prevention and treatment.

Objective To investigate the antibacterial properties of R.lnPGRP-SC1a in Rhipicephalus linnaei, and to provide a reference for the functional analysis of peptidoglycan recognition proteins (PGRPs) within the context of tick innate immunity. Methods Specific primers were meticulously designed based on the coding region sequence, followed by the extraction of tick RNA of adult ticks and its reverse transcription into cDNA. The R.lnPGRP-SC1a gene fragment was subsequently amplified via PCR and then ligated into the plasmid pET32a+, thereby constructing the recombinant expression vector pET32a+-R.lnPGRP-SC1a. This expression vector was then transferred into E.coli BL21 (DE3) competent cells and induced with an IPTG concentration of 0.2 mmol/L at low temperature to enhance protein expression in the supernatant, thereby obtaining a soluble protein with stronger activity. Subsequently, the inhibitory effect of the supernatant protein against two common pathogenic bacteria, E.coli and S.aureus, was assessed using the agar diffusion method. Results The amplified gene fragment was 627 bp in length, and the prokaryotic expression vector pET32a+-R.lnPGRP-SC1a was successfully constructed. Low-temperature induction showed that the recombinant protein was soluble protein, with an approximate molecular weight of 23.63 kD. Antibacterial activity results indicated that, at the same concentration, R.lnPGRP-SC1a exhibited no inhibitory effect on E.coli but demonstrated significant inhibition against S.aureus. Specifically, antibacterial activity became evident at a concentration threshold of 5 mg/mL and increased with the protein concentration. Compared with the inhibitory effects of kanamycin at various concentrations, the inhibitory effect of R.lnPGRP-SC1a at 7 mg/mL was comparable to that of kanamycin at 1 mg/mL. Furthermore, the onset of R.lnPGRP-SC1a inhibitory effect against S.aureus was 2 hours, and the effect lasted for 48 hours. Conclusions This study successfully constructed the R.lnPGRP-SC1a expression vector, its expressed product exhibited persistent activity against Gram-positive bacteria. Thereby, this provides a potential possibility for the development of bioactive bacteriostatic agents.

Objective To perform single-molecule, real-time sequencing of ceftazidime-avibactam (CAZ-AVI)-resistant Pseudomonas aeruginosa and to investigate the mechanism underlying ceftazidime-avibactam resistance in P. aeruginosa. Methods The susceptibility of 89 P. aeruginosa isolates randomly sampled from clinical specimens in Sanming First Hospital Affiliated to Fujian Medical University from November 2021 through July 2023 to common antimicrobial agents was tested, and the minimum inhibitory concentration (MIC) of CAZ-AVI was determined against P. aeruginosa with a broth microdilution assay, with CAZ-AVI MICs of 8 mg/L and lower defined as susceptible and 16 mg/L and higher as resistant. The expression of drug-resistant genes ampC, oxa-488, oprD, mexA, oxa-10, oxa-14, vim and tem was quantified in P. aeruginosa using a real-time quantitative reverse transcription PCR (qPCR) assay. CAZ-AVI-susceptible and -resistant P. aeruginosa isolates from the same case were selected for PacBio single-molecule, real-time sequencing, and sequencing results were subjected to genome structure and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations. Results The 89 P. aeruginosa isolates showed a relatively high level of resistance to meropenem (75.28%) and imipenem (74.16%) and the highest susceptibility to amikacin (91.01%). There were 49 CAZ-AVI-resistant P. aeruginosa isolates and 40 susceptible isolates. qPCR assay detected lower oprD gene expression in CAZ-AVI-resistant P. aeruginosa isolates [0.104 (2.385)] than in susceptible isolates [0.551 (17.885)] (Z = -2.958, P < 0.01), and there were no significant differences between CAZ-AVI-susceptible and -resistant P. aeruginosa isolates in terms of ampC, oxa-488, mexA or tem gene expression (all P values > 0.05), while oxa-10, oxa-14 and vim gene was expressed in few P. aeruginosa isolates. There were 1 729, 3 936, 3 737 and 3 955 genes in CAZ-AVI-resistant P. aeruginosa isolates PA-762 and PA-M174 and susceptible isolates PA-885 and PA-808 that were annotated to GO terms, with the highest numbers of genes enriched in the molecular function of catalytic activity, high numbers of genes enriched in biological processes of metabolic process, single-organism process and cellular process, and high numbers of genes enriched in cellular components of cell and cell membranes. There were 1 803, 4 084, 3 915 and 4 066 genes in the PA-762, PA-M174, PA-885 and PA-808 isolates enriched in the KEGG signaling pathway, and the majority of genes were enriched in four primary signaling pathways of metabolism, genetic information processing, environmental information processing and cellular process, with the highest number of genes associated with metabolic pathways. Both CAZ-AVI-resistant P. aeruginosa isolates PA-762 and PA-M174 carried multiple efflux pumps systems, including MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXY-OprM. Single nucleotide substitution was found at position 169 in the DNA sequence of the PA-762 isolate, leading to substitution of serine for glycine at position 57 in the protein sequence, and there are deletions of two bases at positions 307 and 308 in the DNA sequence of the PA-M174 isolate, leading to substitution of threonine for arginine at position 103 in the protein sequence. Conclusion Mutation or downregulation of oprD gene may lead to CAZ-AVI resistance in P. aeruginosa.

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

Objective:To investigate the impact of lifestyle, apolipoprotein E (ApoE) gene, and their interaction on the risk for cognitive frailty in the elderly population in China.Methods:The study participants were from the Chinese Longitudinal Healthy Longevity Survey. The information about their lifestyles were collected by questionnaire survey, and a weighted lifestyle score was constructed based on β coefficients associated with specific lifestyles to assess the combined lifestyle. ApoE genotypes were assessed by rs429358 and rs7412 single nucleotide polymorphisms. Cognitive frailty was assessed based on cognitive function and physical frailty. Cox proportional hazards regression model was used to analyze the association of lifestyle and ApoE gene with the risk for cognitive frailty and evaluate the multiplicative and additive interactions between lifestyle and ApoE gene. Results:A total of 5 676 elderly persons, with median age [ M ( Q1, Q3)] of 76 (68, 85) years, were included, in whom 615 had cognitive frailty. The analysis by Cox proportional hazards regression model indicated that moderate and high levels of dietary diversity could reduce the risk for cognitive frailty by 18% [hazard ratio ( HR)=0.82, 95% CI: 0.68-1.00] and 28% ( HR=0.72, 95% CI: 0.57-0.91), respectively; moderate and high levels of physical activity could reduce the risk by 31% ( HR=0.69, 95% CI: 0.56-0.85) and 23% ( HR=0.77, 95% CI: 0.64-0.93), respectively. Healthy lifestyle was associated with a 40% reduced risk for cognitive frailty ( HR=0.60, 95% CI: 0.46-0.78). ApoE ε4 allele was associated with a 26% increased risk for cognitive frailty ( HR=1.26, 95% CI: 1.02-1.56). No multiplicative or additive interactions were found between lifestyle and ApoE gene. Conclusions:Dietary diversity and regular physical activity have protective effects against cognitive frailty in elderly population. Healthy lifestyle can reduce the risk for cognitive frailty in elderly population regardless of ApoE ε4 allele carriage status.

Small molecule drug screening technology is continuously evolving and expanding along with drug discovery,and the innovation in drug screening technology can improve the research and development efficiency and success rate,shorten the cycle time,and reduce the cost.From traditional screening technologies based on known active compounds and high-throughput screening(HTS)to new technologies such as structure-based drug discovery(SBDD),fragment-based drug discovery(FBDD),DNA encoded compound library(DEL)and proteolysis targeting chimeras(PROTAC),small molecule drug screening technologies are continuously broadening the market potential for small molecule drugs.This article will provide an overview of the current status of small molecule drug screening technology,systematically review each technique along with their advantages and disadvantages,and offer essential insights for the development of new small molecule drug screening technologies.

Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P＜0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P＜0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P＜0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23％,92.28％,and 91.61％,respectively,and the 5-year DFS were 85.32％,87.90％,and 87.18％,respectively.The differences between the three groups were sta-tistically significant(P＜0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR＞1,P＜0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.

Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P＜0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P＜0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P＜0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23％,92.28％,and 91.61％,respectively,and the 5-year DFS were 85.32％,87.90％,and 87.18％,respectively.The differences between the three groups were sta-tistically significant(P＜0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR＞1,P＜0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.

Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P＜0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P＜0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P＜0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23％,92.28％,and 91.61％,respectively,and the 5-year DFS were 85.32％,87.90％,and 87.18％,respectively.The differences between the three groups were sta-tistically significant(P＜0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR＞1,P＜0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.