Dandouchi Polypeptide Alleviates Depressive-like Behavior and Promotes Hippocampal Neurogenesis by Activating the TRIM67/NF-κB Pathway in CUMS-Induced Mice.

Background: Dandouchi polypeptide (DDCP) is derived from Semen Sojae Praeparatum (Dandouchi in Chinese), a fermented product of Glycine max (L.) Merr. Semen Sojae Praeparatum is widely used in the food industry for its unique flavor and nutritional value, and DDCP, as its derivative, also shows potential health benefits in food applications. However, the specific active substances responsible for Semen Sojae Praeparatum and the underlying mechanisms involved have not been fully elucidated. Methods: DDCP was extracted from Semen Sojae Praeparatum using enzymes, and its antidepressant effects were tested in chronic unpredictable mild stress (CUMS)-induced mice. Immunohistochemistry, immunofluorescence, and western blotting were used to analyze neurogenesis and the nuclear factor κB (NF-κB) pathway. Moreover, an adeno-associated virus (AAV) shRNA was used to induce tripartite motif-containing 67 (TRIM67) deficiency to examine the function of TRIM67 in the neuroprotective effects of DDCP in depressive disorders. Results: DDCP reduced depressive behaviors in CUMS mice and the expression of proinflammatory markers in the hippocampus. DDCP promoted neurogenesis and modulated the TRIM67/NF-κB pathway, with TRIM67 deficiency impairing its antidepressant effect. Conclusions: This research revealed that DDCP has a protective effect on countering depression triggered by CUMS. Notably, TRIM67 plays a crucial role in mitigating depression through DDCP, positioning DDCP as a potential therapeutic option for treating depressive disorders.

Correlation between lipoprotein(a) and recurrent ischemic events post-cerebral vascular stent implantation.

BACKGROUND AND AIM: The association of Lipoprotein(a) (Lp[a]) with recurrent ischemic events in stented patients remains uncertain. So, this research aimed to investigate the impact of elevated Lp(a) levels on the occurrence of ischemic events in this specific patient population. METHODS: Totally 553 patients who underwent intracranial or extracranial artery stent implantation were included. Baseline data were collected and postoperative ischemic outcomes were followed up. Cox regression analysis was used to investigate the association between Lp(a) and outcomes, while accounting for confounding factors. Finally, we established prediction models based on nomogram. RESULTS: Of total 553 patients, a number of 107 (19.3%) experienced outcomes. These included 46 cases (34.7%) in group with elevated Lp(a) levels (>30 mg/dL) and 61 cases (18.4%) in non-elevated group (χ2=6.343, p=0.012). The group with elevated Lp(a) was 1.811 times more likely to experience ischemic events than the non-elevated group, each 1 mg/dL increase in Lp(a) resulted in a 1.008-fold increase in the recurrence rate of ischemic events. In addition, sex (male), previous history of coronary heart disease, decreased albumin, elevated very low density lipoprotein cholesterol and poorly controlled risk factors (including blood pressure and blood sugar) were also associated with a high risk of recurrent ischemic events after stent implantation. CONCLUSION: Lp(a) elevation was a significant risk factor for ischemic events in symptomatic patients who underwent intracranial or extracranial artery stenting.

Confirmation of a measurement model for hospital supply chain resilience.

Background: The hospital supply chain has revealed increasing vulnerabilities and disruptions in the wake of the COVID-19 pandemic, threatening the healthcare services and patient safety. The resilience of hospital supply chains has emerged as a paramount concern within the healthcare system. However, there is a lack of systematic research to develop an instrument tailored to the healthcare industry that is both valid and reliable for measuring hospital supply chain resilience. Therefore, this study aims to construct and validate a comprehensive scale for assessing hospital supply chain resilience, based on dynamic capability theory. Methods: This study followed rigorous scale development steps, starting with a literature review and 15 semi-structured interviews to generate initial items. These items were then refined through expert panel feedback and three rounds of Delphi studies. Using data from 387 hospitals in Province S, mainland China, the scale underwent rigorous testing and validation using structural equation modeling. To ensure the most effective model, five alternative models were examined to determine the most suitable parsimonious model. Results: The study produced a 26-item scale that captures five dimensions of resilience in line with dynamic capability theory: anticipation, adaptation, response, recovery, and learning, all showing satisfactory consistency, reliability and validity. Conclusion: The multi-dimensional scale offers hospital managers a valuable tool to identify areas needing attention and improvement, benchmark resilience against their counterparts, and ultimately strengthen their supply chains against unexpected risks.

Environmental profiles, hazard identification, and toxicological hallmarks of emerging tire rubber-related contaminants 6PPD and 6PPD-quinone.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) is commonly used in rubber compounds as antioxidants to protect against degradation from heat, oxygen, and ozone exposure. This practice extends the lifespan of rubber products, including tires, by preventing cracking, aging, and deterioration. However, the environmental consequences of waste generated during rubber product use, particularly the formation of 6PPD-quinone (6PPD-Q) through the reaction of 6PPD with ozone, have raised significant concerns due to their detrimental effects on ecosystems. Extensive research has revealed the widespread occurrence of 6PPD and its derivate 6PPD-Q in various environmental compartments, including air, water, and soil. The emerging substance of 6PPD-Q has been shown to pose acute mortality and long-term hazards to aquatic and terrestrial organisms at concentrations below environmentally relevant levels. Studies have demonstrated toxic effects of 6PPD-Q on a range of organisms, including zebrafish, nematodes, and mammals. These effects include neurobehavioral changes, reproductive dysfunction, and digestive damage through various exposure pathways. Mechanistic insights suggest that mitochondrial stress, DNA adduct formation, and disruption of lipid metabolism contribute to the toxicity induced by 6PPD-Q. Recent findings of 6PPD-Q in human samples, such as blood, urine, and cerebrospinal fluid, underscore the importance of further research on the public health and toxicological implications of these compounds. The distribution, fate, biological effects, and underlying mechanisms of 6PPD-Q in the environment highlight the urgent need for additional research to understand and address the environmental and health impacts of these compounds.

Rice husk ash based growing media impact on cucumber and melon growth and quality.

Rice husk, an agricultural waste from the rice industry, can cause serious environmental pollution if not properly managed. However, rice husk ash (RHA) has been found to have many positive properties, making it a potential replacement for non-renewable peat in soilless planting. Thus, this study investigated the impact of a RHA composite substrate on the growth, photosynthetic parameters, and fruit quality of cucumber (Yuyi longxiang variety) and melon (Yutian yangjiaomi variety). The RHA, peat, vermiculite, and perlite were blended in varying proportions, with the conventional seedling substrate (peat:vermiculite:perlite = 1:1:1 volume ratio) serving as the control (CK). All plants were cultivated in barrels filled with 10L of the mixed substrates. The results from this study found that RHA 40 (RHA:peat:vermiculite:perlite = 4:4:1:1 volume ratio) significantly enhanced substrate ventilation and positively influenced the stem diameter, root activity, seedling index, chlorophyll content, net photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate (Tr) of cucumber and melon plants. Additionally, plant planted using RHA 40, the individual fruit weight of cucumber and melon found to increase by 34.62% and 21.67%, respectively, as compared to the control. Aside from that, both cucumber and melon fruits had significantly higher sucrose, total soluble sugar, vitamin C, and soluble protein levels. This subsequently improved the activity of sucrose synthase and sucrose phosphate synthase in both cucumber and melon. In conclusion, the RHA 40 found to best promote cucumber and melon plant growth, increase plant leaf photosynthesis, and improve cucumber and melon fruit quality, making it a suitable substrate formula for cucumber and melon cultivation in place of peat.

Tet1/DLL3/Notch1 signal pathway affects hippocampal neurogenesis and regulates depression-like behaviour in mice.

Ten-eleven translocation protein 1 (Tet1) is associated with the regulation of depression-like behaviour in mice. However, the mechanism by which Tet1 affects neurogenesis in mice to regulate depression-like behaviours remains unclear. In this study, the chronic social defeat stress (CSDS) paradigm was constructed by overexpressing Tet1 protein in the mouse hippocampus, and 5-ethynyl-2'-deoxyuridine (EdU, 50 mg/kg) was injected on the seventh day to explore the mechanism of the regulation of the Tet1/Delta-like protein 3 (DLL3)/Notch1 protein pathway in mice hippocampal neurogenesis and its influence on depression-like behaviour. Following CSDS, the expression level of Tet1 decreased significantly. Moreover, due to the downregulation of Tet1 protein, the maintenance of the DNA methylation and demethylation balance was affected, resulting in a significant increase in the methylation levels of Notch1 and DLL3 and a significant decrease in the protein expression levels of DLL3, Notch1, and brain-derived neurotrophic factor (BDNF). At the same time, the proliferation and differentiation of neurones were affected, which was related to a significant decrease in the number of EdU+, doublecortin (DCX)+, and Ki67+ cells in the hippocampus of the CSDS model mice. When the Tet1 protein was overexpressed in the mouse hippocampus, DLL3 and Notch1 protein expression levels were upregulated, promoting hippocampal neurogenesis and alleviating depression-like behaviour in mice. These findings suggest that regulation of the hippocampal Tet1/DLL3/Notch1 protein pathway to influence neurogenesis may be a therapeutic strategy for depression.

Didactical approaches and insights into environmental processes and cardiovascular hazards of arsenic contaminants.

Arsenic, as a metalloid, has the ability to move and transform in different environmental media. Its widespread contamination has become a significant environmental problem and public concern. Arsenic can jeopardize multiple organs through various pathways, influenced by environmental bioprocesses. This article provides a comprehensive overview of current research on the cardiovascular hazards of arsenic. A bibliometric analysis revealed that there are 376 papers published in 145 journals, involving 40 countries, 631 institutions, and 2093 authors, all focused on arsenic-related concerns regarding cardiovascular health. China and the U.S. have emerged as the central hubs of collaborative relationships and have the highest number of publications. Hypertension and atherosclerosis are the most extensively studied topics, with redox imbalance, apoptosis, and methylation being the primary mechanistic clues. Cardiovascular damage caused by arsenic includes arrhythmia, cardiac remodeling, vascular leakage, and abnormal angiogenesis. However, the current understanding is still inadequate over cardiovascular impairments, underlying mechanisms, and precautionary methods of arsenic, thus calling an urgent need for further studies to bridge the gap between environmental processes and arsenic hazards.

Validation of China Health-Related Outcomes Measures-Cardiovascular Disease.

OBJECTIVES: China Health-Related Outcomes Measures (CHROME) was an initiative aimed at developing a system of preference-based health-related quality of life instruments for China. CHROME-cardiovascular disease (CVD) is a CVD-specific instrument with 14 items developed under this initiative. This study aimed to test the psychometric properties of CHROME-CVD. METHODS: This validation study was conducted using cross-sectional questionnaire survey in China. Eligible patients with CVD were recruited and asked to complete the CHROME-CVD, the EQ-5D-5L, and a CVD-specific nonpreference-based health-related quality of life instrument selected according to the confirmed diagnosis of the patients. Item evaluation, internal consistency, measurement invariance, test-retest reliability, structural validity, and construct validity were tested using classic test theory. Item response theory was used to evaluate item-level performance. RESULTS: A total of 444 patients with CVD (coronary artery disease, n = 276, heart failure, n = 104, angina, n = 33, and atrial fibrillation, n = 16) from 6 provinces in China were enrolled for the validation. Exploratory factor analysis identified 4 factors: chest pain, other symptoms, physical health, and mental and social health. Cronbach's alpha and intraclass correlation coefficient were >0.8. A total of 20 of 26 (76.9%), and 90 of 95 (94.7%) predefined hypotheses were met for convergent and discriminant validities, respectively. No important difference was identified between subgroups of gender and residency. Response options of 10 items were found overlapped based on categorical response curves, which led to modification to 4-level response options. Wording of 3 items were modified by referring wordings of reference instruments. CONCLUSION: The validation of the CHROME-CVD demonstrated generally good psychometric properties. Further validation on the modified CHROME-CVD is needed.

Saikosaponin-d alleviates depression by promoting NLRP3 ubiquitination and inhibiting inflammasome activation.

Saikosaponin-d (SSd) is a triterpene saponin from the roots of Bupleurum chinese. Recent studies have revealed its antidepressant activity, but its mechanism involved is unclear. This study's objective was to ascertain how SSd may reduce depression in depressed mice subjected to chronic unpredictable animal stress (CUMS) and to investigate the mechanisms underlying these effects. Models of CUMS depression were established and different groups were treated with SSd and escitalopram. After the last day of administration of the treatment, behavioral tests were performed. ELISA was used to measure the expression of IL-1ß, TNF-α, and IL-18, and western blot was used to measure the presence of proteins associated with NLRP3. Hippocampal neuronal damage was observed using Nissl staining, and NLRP3 ubiquitination assay was performed by immunoprecipitation and gene silencing. An inflammatory cell model was constructed by treating BV2 cells with lipopolysaccharides (LPS) and adenosine triphosphate (ATP) to verify the ubiquitination modification of NLRP3 by SSd. Behavioral tests demonstrated that SSd effectively alleviated depression-like symptoms. SSd should substantially limit the degrees of proteins associated with NLRP3, as properly as limit the harm to hippocampal neurons. Gene silencing results showed that SSd regulates NLRP3 through the E3 ubiquitin ligase MARCHF7. In vitro, SSd remarkably increased the protein expression of K48-linked ubiquitin in inflammatory BV2 cells, while decreasing the protein levels of NLRP3. Our findings suggest that SSd has antidepressant effects in CUMS mice by promoting ubiquitination of NLRP3 to inhibit inflammasome activation and improve the inflammatory state.

A polypeptide derived from pilose antler ameliorates CUMS-induced depression-like behavior by SENP2-PLCß4 signaling axis.

Neurogenesis is known to be closely associated with depression. We aimed to investigate whether a polypeptide monomer derived from pilose antler (polypeptide sequence LSALEGVFYP, PAP) exerts an antidepressant effect by influencing neurogenesis, and to elucidate the mechanism of its antidepressant action. Behavioral tests were performed to observe the antidepressant effect of PAP. Neurogenesis in the dentate gyrus (DG) region of hippocampus was observed by immunofluorescence. The expression of key proteins of Sentrin/SUMO-specific proteases 2 (SENP2)- Phosphoinositide-specific phospholipase C beta 4 (PLCß4) pathway was accessed by co-immunoprecipitation (Co-IP), and the calcium homeostasis associated proteins were observed via Western blot (WB). Subsequently, temozolomide (TMZ) pharmacologically blocked neurogenesis to verify the antidepressant effect of PAP on neurogenesis. The mechanism of PAP antidepressant effect was verified by constructing a sh-SENP2 virus vector to silence SENP2 protein. Finally, corticosterone (CORT)-induced PC12 cell model was used to verify whether PAP was involved in the process of deconjugated PLCß4 SUMOylated. The results showed that PAP improved depression-like behavior and neurogenesis induced by chronic unpredictable mild stimulation (CUMS). In addition, PAP acted on SENP2-PLCß4 pathway to deconjugate the SUMOylation of PLCß4 and affect calcium homeostasis. Pharmacological blockade of neurogenesis by TMZ treatment impaired the antidepressant efficacy of PAP. Knockout of SENP2 in the CUMS model attenuated the antidepressant response of PAP, and the impaired neurogenesis was not ameliorated by PAP treatment. In summary, PAP acted on the SENP2-PLCß4 signaling pathway to inhibit the SUMOylation of PLCß4 and maintain calcium homeostasis, thereby protecting neurogenesis and playing an antidepressant role.

The association between Helicobacter pylori and gastrointestinal disorders during pregnancy: A Multicenter retrospective study.

BACKGROUND: Some gastrointestinal disorders may be associated with Helicobacter pylori infection, which not only affect maternal health, but may also lead to adverse pregnancy outcomes. We aim to explore the association between H. pylori and gastrointestinal disorders in pregnant women. MATERIALS AND METHODS: In total, 503 patients were retrospectively analyzed and divided into the H. pylori-uninfected group, the H. pylori-infected group, or the H. pylori-eradicated group. We analyzed the influence of H. pylori on gastrointestinal diseases during pregnancy among the groups, as well as the severity, symptoms, laboratory tests of the H. pylori-related diseases. RESULTS: Pregnant women with H. pylori infection had higher risk of nausea and vomiting of pregnancy (NVP) (p < 0.001), severe NVP(p = 0.012), hyperemesis gravidarum (p = 0.027), hematemesis (p = 0.018), hyponatremia (p = 0.033), as well as functional dyspepsia symptoms including epigastric pain (p = 0.004), bloating (p = 0.024), and feeling full quickly in a meal (p = 0.031) compared with those without H. pylori infection. While the prevalence of NVP (p = 0.024), severe NVP (p = 0.009), epigastric pain (p = 0.037), and bloating (p = 0.032) were lower in H. pylori-eradicated pregnant women than in H. pylori-infected women. In addition, pregnant women with H. pylori infection had higher risk of spontaneous preterm birth than whom without H. pylori infection (p = 0.033). CONCLUSIONS: Helicobacter pylori infection was associated with higher risks of NVP, severe NVP, hyperemesis gravidarum, functional dyspepsia, and spontaneous preterm birth in pregnant women.

A novel immune-related prognostic signature based on Chemoradiotherapy sensitivity predicts long-term survival in patients with esophageal squamous cell carcinoma.

Background: There is a heterogenous clinical response following chemoradiotherapy (CRT) in esophageal squamous cell carcinoma (ESCC). Therefore, we aimed to study signaling pathway genes that affect CRT sensitivity and prognosis. Methods: Gene expression analyses were performed in the GEO and TCGA datasets. A immunohistochemistry (IHC) analysis was performed in pretreatment biopsies. Results: MMP13 was found to be highly expressed in the "Pathologic Complete Response (pCR)" and "Complete Remission (CR)" and "Alive" groups. Th17 cells and MMP9/13 showed a negative correlation in immune infiltration analysis. In GSEA analysis, IL-4 and IL-13 signaling pathways were highly enriched in patients exhibiting high MMP expression in pCR and CR groups. IHC results suggested higher MMP13 & IL-4 and lower IL-17A & RORC expression in the CR group compared to the 0.70, and the model could well distinguish high-risk and low-risk subgroups. Conclusion: The above results may provide guidance for developing novel treatment and prognostic strategies in ESCC patients.

Effect of social integration on family doctor contracting services among migrant populations in China: a national cross-sectional survey.

BACKGROUND: The family doctor (FD) contracting system is a key reform in the development of the Chinese health system, and is considered an effective way to ensure equitable access to healthcare services. This study investigates the effects of social integration on FD contracting services among migrant populations. METHODS: In total, 120,106 respondents from the 2018 China Migrants Dynamic Survey were included in this study. Two multivariate regression models were used to estimate the effect of social integration and other factors on FD contracting services among migrant populations. RESULTS: This study found that only 14.0% of the migrant populations had a FD. Multiple dimensions of social integration and some covariates were shown to be positively associated with FD contracting services, including average monthly household income, local medical insurance (odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.29-1.39), employment status (OR = 0.86, 95% CI = 0.82-0.91), settlement intention (OR = 1.15, 95% CI = 1.09-1.22), received health education (OR = 4.88, 95% CI = 4.51-5.27), sex (OR = 1.16, 95% CI = 1.12-1.20), age (OR = 1.66, 95% CI = 1.51-1.82), marital status (OR = 1.38, 95% CI = 1.31-1.46), sickness within a year (OR = 0.84, 95% CI = 0.79-0.89), and flow range (OR = 1.12, 95% CI = 1.07-1.16). CONCLUSIONS: All dimensions of social integration, including economic integration, social identity, and social involvement, are associated with FD contracting services among migrant populations. Policymakers should focus on improving the signing rates of migrant populations and implement more effective measures to enhance their social integration, such as settlement incentives and encouraging social participation.

DSC2 suppresses the growth of gastric cancer through the inhibition of nuclear translocation of γ-catenin and PTEN/PI3K/AKT signaling pathway.

BACKGROUND: Globally, gastric cancer (GC) is still a major leading cause of cancer-associated deaths. Downregulated desmocollin2 (DSC2) is considered to be closely related to tumor progression. However, the underlying mechanisms of DSC2 in GC progression require further exploration. METHOD: We initially constructed different GC cells based on DSC2 contents, established the mouse tumor xenografts, and subsequently performed clonal formation, MTT, Caspase-3 activity, and sperm DNA fragmentation assays to detect the functions of DSC2 in GC growth. Subsequently, we performed western blot, Co-IP, and immunofluorescence assays to investigate the underlying mechanisms through pretreatment with PI3K inhibitor, LY294002, and its activator, recombinant human insulin-like growth factor I (IGF1). RESULT: DSC2 could significantly inhibit the viability of GC cells at both in vitro and in vivo levels. The underlying mechanism may be that DSC2 binds the γ-catenin to decrease its nuclear level, thereby downregulating the anti-apoptotic factor BCL-2 expression and upregulating the pro-apoptotic factor P53 expression, which adjusts the PTEN/PI3K/AKT signaling pathway to promote the cancer cell apoptosis. CONCLUSIONS: Our finding suggests that DSC2 might be a potential therapeutic target for the treatment of cancers, most especially GC.

A Surrogate Endpoint for Overall Survival in Locally Advanced and Resectable Esophageal Squamous Cell Carcinoma: A Reanalysis of Data From the NEOCRTEC5010 Trial.

PURPOSE: This study aimed to investigate disease-free survival (DFS) as a surrogate endpoint for overall survival (OS) in patients with locally advanced and resectable esophageal squamous cell carcinoma. METHODS AND MATERIALS: We re-analyzed patient data from the NEOCRTEC5010 randomized controlled trial (N = 451 patients) to compare their OS with that of an age- and sex-matched cohort from the general population of China. We used expected survival and the standardized mortality ratio, respectively, in our analysis of data collected from a neoadjuvant chemoradiation therapy (NCRT) plus surgery group and a surgery-only group. Published data from 6 randomized controlled trials and 20 retrospective studies were used to examine the correlation between DFS and OS at the trial level. RESULTS: The annual hazard rate of disease progression decreased to 4.9% and 8.1% within 3 years in the NCRT and surgery groups, respectively. Patients who were disease-free at 36 months had a 5-year OS of 93.9% (95% CI, 89.7%-98.4%) in the NCRT group with a standardized mortality ratio of 1.1 (95% CI, 0.7-1.8; P = .5639). In contrast, the 5-year OS was only 12.9% (95% CI, 7.3%-22.6%) for patients in the NCRT group who exhibited disease progression within 36 months. At the trial level, DFS and OS were correlated with treatment effect (R2 = 0.605). CONCLUSIONS: Disease-free status at 36 months is a valid surrogate endpoint for 5-year OS in patients with locally advanced and resectable esophageal squamous cell carcinoma. Patients who were disease-free at 36 months showed a favorable OS, which was indistinguishable from that of the age- and sex-matched comparison group from the general population; otherwise, their 5-year OS was extremely poor.

Newly discovered developmental and ovarian toxicity of 3-monochloro-1,2-propanediol in Drosophila melanogaster and cyanidin-3-O-glucoside's protective effect.

3-Monochloro-1,2-propanediol (3-MCPD) is a pervasive environmental pollutant that is unintentionally produced during industrial production and food processing. Although some studies reported the carcinogenicity and male reproduction toxicity of 3-MCPD thus far, it remains unexplored whether 3-MCPD hazards to female fertility and long-term development. In this study, the model Drosophila melanogaster was employed to evaluate risk assessment of emerging environmental contaminants 3-MCPD at various levels. We found that flies on dietary exposure to 3-MCPD incurred lethality in a concentration- and time-dependent way and interfered with metamorphosis and ovarian development, resulting in developmental retardance, ovarian deformity and female fecundity disorders. Mechanistically, 3-MCPD caused redox imbalance observed as a drastically increased oxidative status in ovaries, confirmed by increased reactive oxygen species (ROS) and decreased antioxidant activities, which is probably responsible for female reproductive impairments and developmental retardance. Intriguingly, these defects can be substantially prevented by a natural antioxidant, cyanidin-3-O-glucoside (C3G), further confirming a critical role of ovarian oxidative damage in the developmental and reproductive toxicity of 3-MCPD. The present study expanded the findings that 3-MCPD acts as a developmental and female reproductive toxicant, and our work provides a theoretical basis for the exploitation of a natural antioxidant resource as a dietary antidote for the reproductive and developmental hazards of environmental toxicants that act via increasing ROS in the target organ.

Synthesis of gallic acid amide derivatives containing 1,3,4-thiadiazole and their inhibitory activity on Vibrio harveyi.

Using Gallic acid as raw material, 1-(substituted aromatic acyl)-4-(3,4,5-trihydroxybenzoyl) thiosemicarbazone was prepared by a two-step reaction and a series of brand-new gallic acid amide derivatives that contained 1,3,4-thiadiazole were synthesized by cyclic reaction. The newly prepared compounds' Vibrio harveyi inhibition activities were evaluated. The results indicated that all compounds showed different degree of inhibitory activity on Vibrio harveyi. Among them, the best inhibition effect was shown by compound 5b and its minimum inhibitory concentration (MIC) was 0.0313mg/mL.

Electrically Modulated Nanofiltration Membrane Based on an Arch-Bridged Graphene Structure for Multicomponent Molecular Separation.

Tunable regulation of molecular penetration through porous membranes is highly desirable for membrane applications in the pharmaceutical and medical fields. However, in most previous reports additional reagents or components are usually needed to provide the graphene-based membranes with responsiveness. Herein, we report tunable arch-bridged reduced graphene oxide (rGO) nanofiltration membranes modulated by the applied voltage. Under a finite voltage of 5 V, the rGO membrane could completely reject organic/anionic molecules. With assistance of the voltage, the positive-charge-modified rGO membrane realized the universal rejection of both cationic and anionic dyes, also showing the valid modulation in harsh organic solvents. The efficient electrical modulation depended on the synergetic effects of Donnan repulsion and size exclusion, benefiting from the electric field enhancement in arch-bridged rGO structures. Furthermore, multicomponent separation was achieved by our electrically modulated rGO-based membranes, demonstrating their potential in practical applications such as pharmaceutical industries.

Inhibition of IL-6 methylation by Saikosaponin C regulates neuroinflammation to alleviate depression.

PURPOSE: Saikosaponin C (SSc) increases the expression of synaptic proteins and has a unexplored role in the prevention of AD and other neurodegeneration in humans. Therefore, we hypothesized that SSc has the potential to relief of depressive symptoms. Here, our study assessed the role of SSc on depression-like behaviors caused by a chronic social defeat stress (CSDS) in mice and explored the underlying mechanisms. METHODS: Behavioral tests were conducted to verify the efficacy of SSC in treating depression-like behavior in mice. The levels of IL-6, TNF-α and IL-1ß in brain tissue and BV2 cells were determined by ELISA. The effect of SSc on dendritic spine density was determined by Golgi staining. The percentage of monocytes in peripheral blood was measured using flow cytometry. The levels of STAT3 and DNMT1 under the influence of SSc were assessed by immunofluorescence. Protein expression of DNMT1, DNMT3a, DNMT3b, p-STAT3 and STAT3 in brain and BV2 cells was studied by Western blot. OE-DNMT1 was induced in the experiment to verify the inhibitory effect of DNMT1 on IL-6 methylation in SSC. Luciferase was used to detect SSC specific fragments affecting IL-6 methylation. RESULT: SSC treatment significantly alleviated depressive-like behavior, inhibited the levels of inflammatory cytokines including IL-6, IL-1ß and TNF-α, increased dendritic spine density and promoted synaptic plasticity in mice. SSC downregulated IL-6, STAT3 and DNMT1 expression in vivo and in vitro. SSC also decreased the percentage of monocytes in peripheral blood and suppressed neuroinflammation in mice. Overexpression of DNMT1 by shRNA abolished the inhibitory effect of SSc on IL-6 methylation. CONCLUSION: This study showed that SSc reduced IL6 methylation by inhibiting DNMT1 protein, induced a decrease in IL6 expression, promoted synaptic plasticity, and attenuated CSDS-induced depression-like behavior.

Identification on surrogating overall survival with progression-free survival of first-line immunochemotherapy in advanced esophageal squamous cell carcinoma-an exploration of surrogate endpoint.

BACKGROUND: Overall survival (OS) is the gold standard to assess novel therapeutics to treat cancer. However, to identify early efficacy and speed up drug approval, trials have used progression-free survival (PFS) as a surrogate endpoint (SE). Herein, we aimed to examine if PFS could function as an OS surrogate in advanced Esophageal Squamous Cell Carcinoma (ESCC) treated with first-line immunochemotherapy. METHODS: Two hundred ninety-two advanced ESCC patients treated using inhibitors of PD-1/PD-L1 + chemotherapy or chemotherapy alone were collected. In addition, six phase III randomized clinical trials were eligible for inclusion. Bayesian normal-induced-copula-estimation model in retrospective patient data and regression analysis in the published trial data were used to determine the PFS-OS correlation. RESULTS: PFS correlated moderately with OS in the retrospective cohort (Kendall's Tau = 0.684, τ = 0.436). In trial-level, treatments effects for PFS correlated weakly with those for OS in intention-to-treat population (R2 = 0.436, adj.R2 = 0.249, P > 0.05) and in PD-L1-enriched population (R2 = 0.072). In arm-level, median PFS also correlated weakly with median OS. Moreover, analysis of the retrospective cohort demonstrated that the annual death risk after progression in the continued immunotherapy group was considerably lower than that in the discontinued group. CONCLUSION: In trials of anti-PD-1 agents to treat advanced ESCC, the current results provide only weak support for PFS as an OS surrogate; OS cannot be substituted completely by PFS in these cases. The results also suggest that qualified patients with advanced ESCC might benefit from continuous immunotherapy beyond progression to achieve a decreased risk of death.