Evaluation of antitumor potential of an anti-glypican-1 monoclonal antibody in preclinical lung cancer models reveals a distinct mechanism of action.

Aim: The main objective of this study was to investigate the antitumor effect of a mouse anti-human glypican-1 (GPC1) monoclonal antibody (mAb) on non-small cell lung carcinoma (NSCLC) and associated molecular mechanisms. Methods: The anti-proliferative and anti-migratory activities of anti-GPC1 mAb were examined in A549 and H460 NSCLC cells and LL97A lung fibroblasts. The inhibitory effect of anti-GPC1 mAb on tumor growth was evaluated in an orthotopic lung tumor model. Results: The in vitro study showed that anti-GPC1 mAb profoundly inhibited the anchorage-independent growth of A549 and H460 NSCLC cells and exhibited relatively high cytotoxic activities towards LL97A lung fibroblasts, A549/LL97A and H460/LL97A coculture spheroids. Moreover, anti-GPC1 mAb significantly decreased the expression of phospho-Src (p-Src; Tyr416), p-Akt (Ser473) and ß-catenin in the co-cultured LL97A lung fibroblasts, and the expression of phospho-mitogen-activated protein kinase kinase (p-MEK; Ser217/221) and phospho-90 kDa ribosomal s6 kinase (p-p90RSK; Ser380) in co-cultured A549 cells. When anti-GPC1 mAb was administered to tumor-bearing mice, the inhibitory effect of anti-GPC1 mAb on the orthotopic lung tumor growth was not statistically significant. Nonetheless, results of Western blot analysis showed significant decrease in the phosphorylation of fibroblast growth factor receptor 1 (FGFR1) at Tyr766, Src at Tyr416, extracellular signal-regulated kinase (ERK) at Thr202/Tyr204, 90 kDa ribosomal S6 kinase (RSK) at Ser380, glycogen synthase kinases 3α (GSK3α) at Ser21 and GSK3ß at Ser9 in tumor tissues. These data implicate that anti-GPC1 mAb treatment impairs the interaction between tumor cells and tumor associated fibroblasts by attenuating the paracrine FGFR signal transduction. Conclusions: The relatively potent cytotoxicity of anti-GPC1 mAb in lung fibroblasts and its potential inhibitory effect on the paracrine FGFR signal transduction warrant further studies on the combined use of this mAb with targeted therapeutics to improve therapeutic outcomes in lung cancer.

Religion, Geography, and Risky Sexual Behaviors Among International Immigrants Living in China: Cross-Sectional Study.

Background: Behavioral differences exist between countries, regions, and religions. With rapid development in recent decades, an increasing number of international immigrants from different regions with different religions have settled in China. The degrees to which sexual behaviors-particularly risky sexual behaviors-differ by religion and geographical areas are not known. Objective: We aim to estimate the associations of religion and geographical areas with sexual behaviors of international immigrants and provide evidence for promoting the sexual health of international immigrants. Methods: A cross-sectional study was conducted via the internet with a snowball sampling method among international immigrants in China. In our study, risky sexual behaviors included having multiple sexual partners and engaging in unprotected sex. Descriptive analysis was used to analyze the basic characteristics of international immigrants as well as their sexual behaviors, religious affiliations, and geographical regions of origin. Multivariate binary logistic regression analyses with multiplicative and additive interactions were used to identify aspects of religion and geography that were associated with risky sexual behaviors among international immigrants. Results: A total of 1433 international immigrants were included in the study. South Americans and nonreligious immigrants were more likely to engage in risky sexual behaviors, and Asian and Buddhist immigrants were less likely to engage in risky sexual behaviors. The majority of the Muslims had sexually transmitted infection and HIV testing experiences; however, Muslims had a low willingness to do these tests in the future. The multivariate analysis showed that Muslim (adjusted odds ratio [AOR] 0.453, 95% CI 0.228-0.897), Hindu (AOR 0.280, 95% CI 0.082-0.961), and Buddhist (AOR 0.097, 95% CI 0.012-0.811) immigrants were less likely to report engaging in unprotected sexual behaviors. Buddhist immigrants (AOR 0.292, 95% CI 0.086-0.990) were also less likely to have multiple sexual partners. With regard to geography, compared to Asians, South Americans (AOR 2.642, 95% CI 1.034-6.755), Europeans (AOR 2.310, 95% CI 1.022-5.221), and North Africans (AOR 3.524, 95% CI 1.104-11.248) had a higher probability of having multiple sexual partners. Conclusions: The rates of risky sexual behaviors among international immigrants living in China differed depending on their religions and geographical areas of origin. South Americans and nonreligious immigrants were more likely to engage in risky sexual behaviors. It is necessary to promote measures, including HIV self-testing, pre-exposure prophylaxis implementation, and targeted sexual health education, among international immigrants in China.

Regulation of reactive species during ionizing radiation by peroxydisulfate for enhanced degradation of typical pollutants in coking wastewater.

This study focused on exploring the effect of peroxydisulfate (PDS) on the regulation of reactive species during water radiolysis process and its potential application for degrading organic pollutants. The results indicated that PDS was successfully activated by ionizing radiation for efficient removal of three typical phenolic compounds over a wide pH range (3.0∼12.0) at absorbed dose of 5 kGy. Chemical probe methods provided the evidence that the addition of PDS could introduce the sulfate radicals (SO4•-) and enhance the production of hydroxyl radicals (•OH). According to the quenching tests, •OH and SO4•- were the dominant reactive species responsible for the degradation of 4-NP, while hydrated electron (eaq-) played a minor role. The regulatory effect of PDS on active species in the ionizing radiation process could divided by (i) PDS could be directly activated by ionizing radiation to produce •OH and SO4•- via energy transfer pathway; (ii) PDS could boost the conversion of eaq- to SO4•- via electron transfer pathway. Furthermore, we assessed the applicability of the IR and IR/PDS systems in treating mixed solutions containing various pollutants and actual coking wastewater.

UCHL3 promotes hepatocellular carcinoma progression by stabilizing EEF1A1 through deubiquitination.

BACKGROUND: Hepatocellular carcinoma (HCC) ranks as the second leading cause of global cancer-related deaths and is characterized by a poor prognosis. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) have been proved to play important roles in various human cancers, whereas the deubiquitination of EEF1A1 was poorly understood. METHODS: The binding and regulatory relationship between Ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) and EEF1A1 was validated using clinical tissue samples, reverse transcription quantitative real-time fluorescence quantitative PCR (RT-qPCR), Western blotting, co-immunoprecipitation, and immunofluorescence, as well as ubiquitin detection and cyclohexamide tracking experiments. Finally, the impact of the UCHL3/EEF1A1 axis on HCC malignant behavior was analyzed through functional experiments and nude mouse models. RESULTS: UCHL3 was found to have a high expression level in HCC tissues. Tissue samples from 60 HCC patients were used to evaluate the correlation between UCHL3 and EEF1A1. UCHL3 binds to EEF1A1 through the lysine site, which reduces the ubiquitination level of EEF1A1. Functional experiments and nude mouse models have demonstrated that the UCHL3/EEF1A1 axis promotes the migration, stemness, and drug resistance of HCC cells. Reducing the expression of EEF1A1 can reverse the effect of UCHL3 on the malignant behavior of HCC cells. CONCLUSION: Our findings revealed that UCHL3 binds and stabilizes EEF1A1 through deubiquitination. UCHL3 and EEF1A1 formed a functional axis in facilitating the malignant progression of HCC, proving new insights for the anti-tumor targeted therapy for HCC.

Profiling the volatile compounds of Peganum harmala L. Based on multiple sample preparation coupled with gas chromatography-mass spectrometry analysis and explored its antidepressants-like activity.

Peganum harmala L., a traditional medicinal plant in China, is renowned for its significant alkaloid content in seeds and roots exhibiting a wide range of pharmacological activities, including antidepressant, antiseptic, and antiviral. However, the volatile composition of the herb remained unclear. Apart from that, the extraction of volatile compounds through essential oil presents challenges due to the low yield and the degradation of volatile active compounds at high temperatures. This study used multiple sample preparation methods including headspace (HS), needle trap device (NTD), and liquid-liquid extraction (LLE) coupled with gas chromatography-mass spectrometry (GC-MS) to analyze the volatile compounds from the areal part of P. harmala L.. A total of 93 compounds were identified with NTD facilitating the first detection of harmine among the volatile organic compounds. Through network pharmacology and protein interaction analysis, the compounds' potential therapeutic targets of the compounds were explored, and 23 key targets were obtained (AKT1, ALB, PTGS2, MAOA, etc). KEGG pathway enrichment analysis indicated significant involvement in neuroactive ligand-receptor interactions and serotonergic synapses. The results enhanced the understanding of P. harmala's pharmacological mechanisms and supported its ethnopharmacological use.

The utility of microbiome (microbiota) and exosomes in dentistry.

The concept of the oral-systemic link is important in both basic and clinical dentistry. The microbiome (microbiota) and exosomes are two prevalent issues in the modern medical researches. The common advent of oral and general microbiological investigation originated from the initial observations of oral bacteria within the dental plaque known as oral microbiome. In addition to oral diseases related to oral microbiome, the disruption of the oral and intestinal microbiome could result in the onset of systemic diseases. In the past decade, the exosomes have emerged in the field of the medical researches as they play a role in regulating the transport of intracellular vesicles. However, with the rapid advancement of exosomes researches in recent years, oral tissues (such as dental pulp stem cells and salivary gland cells) are used as the research materials to further promote the development of regenerative medicine. This article emphasized the importance of the concept of the oral-systemic link through the examples of microbiome (microbiota) and exosomes. Through the researches related to microbiome (microbiota) and exosomes, many evidences showed that as the basic dentistry developed directly from the assistance of the basic medicine, indirectly the progress of the basic dentistry turns back to promote the development of the basic medicine, indicating the importance of the concept of the oral-systemic link. The understanding of the oral-systemic link is essential for both clinicians and medical researchers, regardless of their dental backgrounds.

Ethnicity, gender, and geographical distribution of dentists in Taiwan in 1939 (Showa 14).

Background/purpose: Taiwan's dentistry entered into a new era of modernization and flourished during the Japanese colonial period. However, we know very little about the composition of dentists at that time. This study attempted to analyze the ethnicity, gender, and geographical distribution of dentists in Taiwan in 1939 (Showa 14). Materials and methods: The methods of documentary analysis and secondary data analysis were adopted to find the composition of dentists during the late Japanese colonial period through a name list of contract dentists for the Postal Savings Insurance published in August 1939 (Showa 14) by the Taiwan Government Transportation Department Information Bureau. Results: The total number of contract dentists was 368, accounting for 86.79% of the 424 practicing dentists in Taiwan in 1939 (Showa 14). Of the 368 contract dentists (328 males and 40 females), 225 (61.14%) were Taiwanese and 143 (38.86%) were Japanese. Among the 8 prefectures in Taiwan, Tainan Prefecture had the largest number of dentists (97), followed by Taipei (84) and Taichung (78) prefectures. The number of contract dentists per 100,000 people was 6.24, equivalent to 16,021 people served by each contract dentist in 1939 (Showa 14). The chi-square test for the trend analysis of gender distribution indicated a significantly higher proportion of male than female contract dentists in either Taiwanese or Japanese ethnic group. Conclusion: In the late Japanese colonial period, the number of Taiwanese dentists exceeded that of Japanese dentists. Furthermore, there were more male than female dentists in either the Taiwanese or the Japanese population.

Benefits and Risks of Preprepared Parenteral Nutrition for Early Amino Acid Administration in Premature Infants with Very Low Birth Weight.

Purpose: Administering early parenteral amino acids to very low birth weight (VLBW) premature infants (birth body weight [BBW]<1,500 g) is challenging due to factors such as holidays, cost, and access to sterile compounding facilities. Using advance-prepared parenteral nutrition (PN) may address this issue and should be evaluated for its safety and potential benefits. Methods: We extracted data from medical records collected between July 2015 and August 2019. VLBW infants received PN for at least seven days and were split into two groups: the traditional group (n=30), which initially received a glucose solution and then PN on workdays, and the pre-preparation group (n=16), which received advance-prepared PN immediately upon admission to the neonatal intensive care unit. Results: The median BBWs of the traditional and pre-preparation groups were 1,180.0 vs. 1,210.0 g. In the initial two days, the pre-preparation group had a significantly higher amino acid intake (2.23 and 2.24 g/kg/d) than the traditional group (0 and 1.78 g/kg/d). The pre-preparation group exhibited greater head circumference growth ratio relative to birth (7th day: 1.21% vs. -3.57%, p=0.014; 21st day: 7.71% vs. 3.31%, p=0.017). No significant differences in metabolic tolerance were observed. Conclusion: Advanced preparation of PN can be safely implemented in VLBW preterm infants, offering advantages such as early, higher amino acid intake and improved head circumference growth within the first 21 days post-birth. This strategy may serve as a viable alternative in settings where immediate provision of sterile compounding facilities is challenging.

Depressive symptoms and its multifaceted associated factors among young men who have sex with men facing the dual threats of COVID-19 and mpox in China.

INTRODUCTION: The COVID-19 pandemic has significantly impacted the mental health of human beings since 2020, especially the young people and the pre-existing marginalized groups such as men who have sex with men (MSM). During the COVID-19 pandemic, the multi-country outbreak of mpox in 2022 additionally posed a significant stress on the most-affected communities (i.e., MSM). This study investigated the level of depressive symptoms and its multifaceted associated factors among Chinese young men who have sex with men (YMSM) in this unique period. METHODS: In September 2022, a large-scale cross-sectional survey was conducted among YMSM aged 18-29 years across six representative provinces in China. Hierarchical regression analysis was performed to test the various types of associated factors of depressive symptoms. RESULTS: Among the 2493 participants, 65.6 % (n = 1638) reported mild to severe depressive symptoms. The hierarchical regression analysis identified that depressive symptoms was significantly positively associated with unemployment, having substance use in the past 6 months, a higher level of MSM self-stigma, incompletion of COVID-19 vaccination, greater mpox risk perception, and presence of mpox related-like symptoms. LIMITATIONS: This study used the facility-based sampling method to recruit the participants, which may lead to selection bias. CONCLUSIONS: Chinese YMSM faced significant mental health challenges during the concurrent epidemics of COVID-19 and mpox, which was associated with their socio-economic status, risk behaviors, stigma, and multiple diseases-related variables. Proactive measures may hold promise as effective strategies for mitigating mental distress among marginalized groups during public health crises.

The impact of family doctor contract services on the utilization of and satisfaction with primary health care among Chinese residents: A cross-sectional study.

Introduction: Family doctor contract service (FDCS) is a vital part of China's primary health care system. This study aims to explore whether contracting with FDCS affects residents' utilization of and satisfaction with primary health care. Methods: A structured questionnaire was employed to collect data in January 2022. The questionnaire mainly included the following three parts: the social-demographic characteristics, health-related information, and utilization of and satisfaction with primary health care. Propensity score matching (PSM) was used to adjust for social-demographic differences between participants who contracted with a family doctor and those who did not. For the matched population, we used the Chi-square test to examine the differences in the utilization of and satisfaction with primary health care between contracted and non-contracted participants. Moreover, multiple logistic regression and linear regression were used to explore the influencing factors of the utilization of and satisfaction with primary health care. Results: A total of 10,850 people were investigated and 10,419 participants were incorporated into the data analysis. After matching, there were no significant differences in most of the matching variables between the contracted and non-contracted groups (P > 0.05). The utilization rate was significantly higher among the contracted population than of the non-contracted (96.3% vs 92.6%, P < 0.001). The quality of services (e.g., good service attitude, high medical level, and a trusted family doctor) was more likely to be cited as the main reasons for the contracted people to utilize primary health care than for the non-contracted. The contracted people were also significantly more satisfied than the non-contracted in all terms of satisfaction. Moreover, people who contracted with a family doctor were more likely to use primary health care with OR = 1.979 (95% CI, 1.511-2.593). Conclusion: The contracted people were more likely to utilize and be satisfied with primary health care than the non-contracted. In addition, the contracted people tended to use primary health care because of the quality of services rather than because of the close distance or short waiting time. Therefore, it is important to further promote the high quality of FDCS to ensure residents' sense of gain and improve their satisfaction.

Efficacy, immunogenicity, and safety of a monovalent mRNA vaccine, ABO1020, in adults: A randomized, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: ABO1020 is a monovalent COVID-19 mRNA vaccine. Results from a phase 1 trial showed ABO1020 was safe and well tolerated, and phase 3 trials to evaluate the efficacy, immunogenicity, and safety of ABO1020 in healthy adults are urgently needed. METHODS: We conducted a multinational, randomized, placebo-controlled, double-blind, phase 3 trial among healthy adults (ClinicalTrials.gov: NCT05636319). Participants were randomly assigned (1:1) to receive either 2 doses of ABO1020 (15 µg per dose) or placebo, administered 28 days apart. The primary endpoint was the vaccine efficacy in preventing symptomatic COVID-19 cases that occurred at least 14 days post-full vaccination. The second endpoint included the neutralizing antibody titers against Omicron BA.5 and XBB and safety assessments. FINDINGS: A total of 14,138 participants were randomly assigned to receive either vaccine or placebo (7,069 participants in each group). A total of 366 symptomatic COVID-19 cases were confirmed 14 days after the second dose among 93 participants in the ABO1020 group and 273 participants in the placebo group, yielding a vaccine efficacy of 66.18% (95% confidence interval: 57.21-73.27, p < 0.0001). A single dose or two doses of ABO1020 elicited potent neutralizing antibodies against both BA.5 and XBB.1.5. The safety profile of ABO1020 was characterized by transient, mild-to-moderate fever, pain at the injection site, and headache. CONCLUSION: ABO1020 was well tolerated and conferred 66.18% protection against symptomatic COVID-19 in adults. FUNDING: National Key Research and Development Project of China, Innovation Fund for Medical Sciences from the CAMS, National Natural Science Foundation of China.

Design of NAMPTs with Superior Activity by Dual-Channel Protein Engineering Strategy.

The nicotinamide phosphoribosyltransferase (NAMPT)-catalyzed substitution reaction plays a pivotal role in the biosynthesis of nucleotide compounds. However, industrial applications are hindered by the low activity of NAMPTs. In this study, a novel dual-channel protein engineering strategy was developed to increase NAMPT activity by enhancing substrate accessibility. The best mutant (CpNAMPTY13G+Y15S+F76P) with a remarkable 5-fold increase in enzyme activity was obtained. By utilizing CpNAMPTY13G+Y15S+F76P as a biocatalyst, the accumulation of ß-nicotinamide mononucleotide reached as high as 19.94 g L-1 within 3 h with an impressive substrate conversion rate of 99.8%. Further analysis revealed that the newly generated substrate channel, formed through crack propagation, facilitated substrate binding and enhanced byproduct tolerance. In addition, three NAMPTs from different sources were designed based on the dual-channel protein engineering strategy, and the corresponding dual-channel mutants with improved enzyme activity were obtained, which proved the effectiveness and practicability of the approach.