Community Engagement in Vaccination Promotion: Systematic Review and Meta-Analysis.

BACKGROUND: Community engagement plays a vital role in global immunization strategies, offering the potential to overcome vaccination hesitancy and enhance vaccination confidence. Although there is significant backing for community engagement in health promotion, the evidence supporting its effectiveness in vaccination promotion is fragmented and of uncertain quality. OBJECTIVE: This review aims to systematically examine the effectiveness of different contents and extent of community engagement for promoting vaccination rates. METHODS: This study was performed in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive and exhaustive literature search was performed in 4 English databases (PubMed, Embase, Web of Science, and Cochrane Library) and 2 Chinese databases (CNKI and Wan Fang) to identify all possible articles. Original research articles applying an experimental study design that investigated the effectiveness of community engagement in vaccination promotion were eligible for inclusion. Two reviewers independently performed the literature search, study selection, quality assessment, and data extraction. Discrepancies were resolved through discussion, with the arbitration of a third reviewer where necessary. RESULTS: A total of 20 articles out of 11,404 records from 2006 to 2021 were retrieved. The studies used various designs: 12 applied single-group pre-post study designs, 5 were cluster randomized controlled trials (RCTs), and 3 were non-RCTs. These studies targeted multiple vaccines, with 8 focusing on children's immunization, 8 on human papillomavirus vaccine, 3 on hepatitis B virus vaccine, and 1 on COVID-19 vaccine. The meta-analysis revealed significant increases in vaccination rates both in pre-post comparison (rate difference [RD] 0.34, 95% CI 0.21-0.47, I2=99.9%, P<.001) and between-group comparison (RD 0.18, 95% CI 0.07-0.29, I2=98.4%, P<.001). The meta-analysis revealed that participant recruitment had the largest effect size (RD 0.51, 95% CI 0.36-0.67, I2=99.9%, P<.001), followed by intervention development (RD 0.36, 95% CI 0.23-0.50, I2=100.0%, P<.001), intervention implementation (RD 0.35, 95% CI 0.22-0.47, I2=99.8%, P<.001), and data collection (RD 0.34, 95% CI 0.19-0.50, I2=99.8%, P<.001). The meta-analysis indicated that high community engagement extent yielded the largest effect size (RD 0.49, 95% CI 0.17-0.82, I2=100.0%, P<.001), followed by moderate community engagement extent (RD 0.45, 95% CI 0.33-0.58, I2=99.6%, P<.001) and low community engagement extent (RD 0.15, 95% CI 0.05-0.25, I2=99.2%, P<.001). The meta-analysis revealed that "health service support" demonstrated the largest effect sizes (RD 0.45, 95% CI 0.25-0.65, I2=99.9%, P<.001), followed by "health education and discussion" (RD 0.39, 95% CI 0.20-0.58, I2=99.7%, P<.001), "follow-up and reminder" (RD 0.33, 95% CI 0.23-0.42, I2=99.3%, P<.001), and "social marketing campaigns and community mobilization" (RD 0.24, 95% CI 0.06-0.41, I2=99.9%, P<.001). CONCLUSIONS: The results of this meta-analysis supported the effectiveness of community engagement in vaccination promotion with variations in terms of engagement contents and extent. Community engagement required a "fit-for-purpose" approach rather than a "one-size-fits-all" approach to maximize the effectiveness of vaccine promotion. TRIAL REGISTRATION: PROSPERO CRD42022339081; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=339081.

A cross-sectional survey on the relationship between workplace psychological violence and empathy among Chinese nurses: the mediation role of resilience.

BACKGROUND: Workplace violence is one of the most serious public health issues worldwide in healthcare occupations, nurse is a profession which faces the greatest risk of exposure to workplace violence among healthcare occupations. OBJECTIVE: The present study aimed to explore the relationship between workplace psychological violence and empathy among Chinese nurses, and further examine the mediation role of resilience in this relationship. METHOD: A cross-sectional survey was conducted among a convenience sample of clinical registered nurses in Xinjiang China from 29 September 2023 to 19 October 2023.The online questionnaire, contained the general information form, the Workplace Psychologically Violent Behaviors Instrument, the Jefferson Scale of Empathy-Healthcare Professionals Version, and the Connor-Davidson Resilience Scale, was used to collect data. The IBM SPSS statistics software version 22.0 was used to perform data analyses in forms of descriptive statistics, correlation analysis, and mediation analysis. RESULT: This survey recruited a convenience sample of 1613 clinical registered nurses aged 22 to 55 years who come from diverse ethnicities and worked in different departments. A total of 534 nurse experienced psychological violent, which yielded a positive rate of 33.1% for psychological violent among nurses. Pearson analysis reported a negative correlation between psychological violences and empathy (r=-0.724, P < 0.01) as well as a negative correlation between psychological violences and resilience (r=-0.681, P < 0.01). Mediation analysis reported that resilience mediated the negative relationship between psychological violence and empathy, the mediation effect accounted for ab/(ab + c') = 23.40% of the total effect. CONCLUSION: This study supported an inverse ralationship between psychological violence and empathy among Chinese nurses where resilience acted as a protective factor to mediated the negative impacts of psychological violences on empathy These results directed health policies and clinical interventions to equip nurses with resilience to copy with and recover from workplace psychological violence.

Age-dependent seasonal growth cessation in Populus.

In temperate and boreal regions, perennial plants adapt their annual growth cycle to the change of seasons. In natural forests, juvenile seedlings usually display longer growth seasons compared to adult trees to ensure their establishment and survival under canopy shade. However, how trees adjust their annual growth according to their age is not known. In this study, we show that age-dependent seasonal growth cessation is genetically controlled and found that the miR156-SPL3/5 module, a key regulon of vegetative phase change (VPC), also triggers age-dependent growth cessation in Populus trees. We show that miR156 promotes shoot elongation during vegetative growth, and its targets SPL3/5s function in the same pathway but as repressors. We find that the miR156-SPL3/5s regulon controls growth cessation in both leaves and shoot apices and through multiple pathways, but with a different mechanism compared to how the miR156-SPL regulon controls VPC in annual plants. Taken together, our results reveal an age-dependent genetic network in mediating seasonal growth cessation, a key phenological process in the climate adaptation of perennial trees.

Selective Reduction of Cysteine Mutant Antibodies for Site-Specific Antibody-Drug Conjugates.

Developing site-specific conjugation technologies for antibody-drug conjugates (ADCs) aims to produce more homogeneous and controlled drug-loaded ADCs to reduce variability and thereby improve the therapeutic index. This article presents a technology that uses cysteine mutant antibodies and mild phosphine-based reductants to prepare site-specific ADCs. The two types of cysteine mutant antibodies, designated C6v1 and C6v2, have one of the interchain disulfide-forming cysteines in the Fab region in the light chain (LC214) or in the heavy chain (HC220) substituted by alanine (or other amino acids), respectively. Certain phosphine-based reductants were found to selectively reduce the "unpaired" cysteines, at the heavy chain (HC220) for C6v1 or at the light chain (LC214) for C6v2 while keeping the interchain disulfide bonds in the hinge region intact, resulting in 90% of DAR2 species and more than 95% of the desired specific conjugation at HC or LC following conjugation to maleimide moieties. The reduction method shows consistent selectivity toward various C6v1 or C6v2 antibody backbones. Sensitivity toward buffer pH for some reductants can be used to optimize reductant reactivity and selectivity. The technology can be further expanded to generate site-specific DAR4 or dual-payload ADCs based on C6v1 or C6v2 antibodies. This technology offers a method to control drug-loading and conjugation sites using a mild one-pot process, as compared to the reduction-oxidation methods used in technologies such as THIOMAB, and shows superior DAR profiles and process simplification as compared to other selective reduction methods.

Virus-Bionic Mesoporous Silica Nanoplatform for Malignant Tumor Inhibition via Effective Cellular Uptake and Precise Drug Delivery.

Over the past few decades, sophisticated nanomaterials have been used as carries for the targeted delivery of therapeutics to solid tumors. However, the low efficiency of intracellular internalization of nanocarriers in current use restricts their biomedical application. In this work, we demonstrate that novel virus-bionic mesoporous-silica-based nanocarriers can be successfully prepared for programmed precise drug delivery. These unique viral mimic nanovesicles not only present virus bionic counterparts and nanostructures, but also have infectious virus-like properties toward tumor cells and tumor tissues. Encouragingly, their large surface area (322.1 m2 /g) endows them with high loading capacity for therapeutic agents, especially, they have more effective gene transfection properties than the commercially available LipoGeneTM transfection reagent. Thanks to their virus-inspired morphology, they exhibit outstanding cellular uptake efficiency with living tumor cells and the ability to invade cells in large quantities with incubation times as short as 5 min, which is much faster than traditional mesoporous silica nanoparticles (mSN) with smooth appearance. Importantly, after doxorubicin (DOX) loading and surface modification of tumor recognition motifs, RGD (Arg-Gly-Asp, vMN@DOX-RGD), the bionic drug-loaded viral mimics elicit potent tumor cell elimination both in vitro and in vivo, greatly exceeding the mSN-based group. Our work paves the way toward virus bionic nanocarrier design for malignant tumor suppression in the clinic.

Tai Chi for the prophylaxis of episodic migraine: protocol of a non-inferiority randomized controlled trial with mechanism exploration.

BACKGROUND: Migraine is a complex neurovascular disorder with considerable clinical, social and economic issues. Tai chi has the potential to be an alternative prophylactic treatment for migraine with high safety since the adverse effects and limited efficacy of available medications. AIMS: The proposed study aims to compare the prophylaxis efficacy of 24-week Tai Chi training on migraine attacks with the standard prophylactic medication; and to explore the mechanism of Tai Chi in preventing migraine attacks by analyzing the associations between changes of migraine attacks and changes of neurovascular functions and inflammatory makers. METHOD: This is a two-arm parallel non-inferiority randomized controlled trial. In total 220 Hong Kong Chinese women aged 18-65 years with diagnosis of episodic migraine will be recruited and randomized to either the Tai Chi training group or the standard prophylactic medication group with 1:1 ratio, and receive the 24 weeks of modified 33-short form Yang-style Tai Chi training and the standard prophylactic medications, respectively. A 24-week follow-up will be implemented for both groups. For efficacy examination, the primary outcome was the frequency of migraine attacks measured by the migraine diary; and for the mechanism exploration, the primary outcome was the volume and number of white matter hyperintensity (WMH) measured by magnetic resonance imaging (MRI). The measurements will be conducted at the baseline, 24th weeks, and 48th weeks. Linear mixed model will be adopted to comprehensively analyze the changes of variables within and between groups. DISCUSSION: Given the importance of reducing disease burden and financial cost of migraine attacks, the findings of this study will provide new insights regarding the role of Tai Chi in alleviating migraine burden and further shed light on the mechanism action of Tai Chi on preventing headache attacks. TRIAL REGISTRATION: ClinicalTrials.gov NCT05690737. Registered on January 28, 2023.

Discovery of ABBV-154, an anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody-Drug Conjugate (iADC).

Stable attachment of drug-linkers to the antibody is a critical requirement, and for maleimide conjugation to cysteine, it is achieved by ring hydrolysis of the succinimide ring. During ADC profiling in our in-house property screening funnel, we discovered that the succinimide ring open form is in equilibrium with the ring closed succinimide. Bromoacetamide (BrAc) was identified as the optimal replacement, as it affords stable attachment of the drug-linker to the antibody while completely removing the undesired ring open-closed equilibrium. Additionally, BrAc also offers multiple benefits over maleimide, especially with respect to homogeneity of the ADC structure. In combination with a short, hydrophilic linker and phosphate prodrug on the payload, this afforded a stable ADC (ABBV-154) with the desired properties to enable long-term stability to facilitate subcutaneous self-administration.

Homologous recombination repair gene mutations in colorectal cancer favors treatment of immune checkpoint inhibitors.

Immune checkpoint inhibitor (ICI) therapy is insensitive for Colorectal cancer (CRC) patients with microsatellite stable (MSS). Genomic data of three CRC cohort, n = 35), and the Cancer Genome Atlas (TCGA CRC cohort, n = 377), were analyzed. A cohort treated with ICIs from Memorial Sloan Kettering Cancer Center (MSKCC CRC cohort, n = 110) and two cases from the local hospital were characterized the impact of the HRR mutation on prognosis of CRC. Homologous recombination repair (HRR) gene mutations were more common in CN and HL cohorts (27.85%; 48.57%) than in TCGA CRC cohort (15.92%), especially in the MSS populations, the frequencies of HRR mutation were higher in CN and HL cohort (27.45%, 51.72%) than in TCGA cohort (6.85%). HRR mutations were associated with high tumor mutational burden (TMB-H). Although HRR mutation uncorrelated with an improved overall survival in the MSKCC CRC cohort (p = 0.97), HRR mutated patients had a significantly improved OS compared to the HRR wildtype population particularly in MSS subgroups (p = 0.0407) under ICI treatment. It probably contributed by a higher neoantigen and increased CD4+ T cell infiltration which found in the TCGA MSS HRR mutated CRC cohort. The similar phenomenon on cases was observed that MSS metastatic CRC patient with HRR mutation seemed more sensitive to ICI after multi-line chemotherapy in clinical practice than HRR wildtype. This finding suggests the feasibility of HRR mutation as an immunotherapy response predictor in MSS CRC, which highlights a potential therapeutic approach for these patients.

The glial perspective of autism spectrum disorder convergent evidence from postmortem brain and PET studies.

OBJECTIVE: The present study aimed to systematically and quantitatively review evidence derived from both postmortem brain and PET studies to explore the pathological role of glia induced neuroinflammation in the pathogenesis of ASD, and discuss the implications of these findings in relation to disease pathogenesis and therapeutic strategies. METHOD: An online databases search was performed to collate postmortem studies and PET studies regarding glia induced neuroinflammation in ASD as compared to controls. Two authors independently conducted the literature search, study selection and data extraction. The discrepancies generated in these processes was resolved through robust discussions among all authors. RESULT: The literature search yielded the identification of 619 records, from which 22 postmortem studies and 3 PET studies were identified as eligible for the qualitative synthesis. Meta-analysis of postmortem studies reported increased microglial number and microglia density as well as increased GFAP protein expression and GFAP mRNA expression in ASD subjects as compared to controls. Three PET studies produced different outcomes and emphasized different details, with one reported increased and two reported decreased TSPO expression in ASD subjects as compared to controls. CONCLUSION: Both postmortem evidences and PET studies converged to support the involvement of glia induced neuroinflammation in the pathogenesis of ASD. The limited number of included studies along with the considerable heterogeneity of these studies prevented the development of firm conclusions and challenged the explanation of variability. Future research should prioritize the replication of current studies and the validation of current observations.

Natural annual transcriptome dynamics of Eucalyptus reveal seasonal adaptation of tropical/sub-tropical trees.

Seasonal environment cues are primary factors that influence a plant's growth and adaptation. The molecular basis of seasonal phenology has been well studied in trees growing in boreal and temperate ecosystems. However, little is known about the molecular phenology of trees belonging to tropical/sub-tropical regions. Here, we characterize the annual transcriptome dynamics of Eucalyptus dunnii, one of the world's most widely planted tropical/sub-tropical hardwoods, in natural environments. Our transcriptome analysis combined with the geographical distribution, environmental cues, microscopic observations and heterologous transformation analyses provides a molecular timetable of seasonal regulatory events of E. dunnii and its planting prospects in China. We further investigated the molecular mechanisms of the flowering phenology of E. dunnii. Our results suggest that low temperature is one of environment triggers for its seasonal flowering. In addition, a comparative transcriptome and cell ultrastructure analysis between Eucalyptus and Populus reveals the molecular bases of different shoot apex growth habits of trees originating from tropical/sub-tropical and boreal/temperate regions. Our study will provide cues for further investigating the molecular mechanisms underlying the seasonal phenology of trees from tropical/sub-tropical regions.

Analysis of the miRNA expression profile of laboratory red crucian carp under low-dose caesium-137 irradiation.

Radiation can cause the differential expression of biological miRNA molecules. This research was based on the development of the laboratory red crucian carp (LRCC) to explore the feasibility of its application in the detection of low-dose ionizing radiation-induced biological damage in aquatic environments and the development of related molecular markers. Adult LRCC were irradiated with caesium-137 at 0.3 Gy, while RNA-seq and bioinformatics techniques were used to identify miRNAs that were differentially expressed relative to their levels in the nonirradiation group. Analysis of liver sections showed that liver cells in the radiation group showed nuclear pyknosis. In this study, 34 miRNAs differentially expressed in the liver of LRCC after irradiation were identified, among which seven were new crucian carp miRNAs; a total of 632 target genes were predicted in the prediction analysis. The results of comprehensive GO enrichment and KEGG pathway analyses showed that these target genes were mainly involved in energy transfer and material catabolism, especially malonyl-CoA biosynthesis, acetyl-CoA carboxylase activity, fatty acid biosynthesis and metabolism, and pyruvate metabolism; in addition, the AMPK signalling pathway was the most active pathway. This study shows that the LRCC is sensitive to radiation, or can be used as a candidate experimental animal to study the biological effects of radiation, and the screened miRNA can be used as a pre-selected biomarker for radiation damage detection and radiation biological environmental monitoring. CLINICAL TRIALS REGISTRATION: None.

Case Report: A Case of Locally Advanced Pancreatic Cancer Which Achieved Progression Free for Over 12 Months by Subsequent Therapy with Anlotinib Hydrochloride Plus Tegafur-Gimeracil-Oteracil Potassium (TS-1).

Titled the "most destructive of all cancers", pancreatic cancer is a malignant tumor with a very poor prognosis and has a poor response to systemic therapy. At present, several studies have shown that tegafur-gimeracil-oteracil potassium (hereinafter referred to as TS-1) is no less superior to gemcitabine in the treatment of advanced pancreatic cancer. In addition, a number of current clinical studies have shown that targeted therapy combined with chemotherapy reflects therapeutic advantages in pancreatic cancer. Moreover, in vitro and in vivo experiments have also demonstrated that anlotinib can curb the proliferation of pancreatic cancer cells and induce their apoptosis. Here, we report for the first time that a patient with locally advanced pancreatic cancer achieved good efficacy after switching to TS-1 chemotherapy combined with anlotinib targeted therapy. Previously, the disease of the patient still rapidly progressed without control following the first switch to abraxane combined with gemcitabine chemotherapy (AG regimen) due to the progression after chemo-radiotherapy. In this case, the patient achieved progression-free survival (PFS) of over 14 months via the treatment with anlotinib targeted therapy combined with TS-1 chemotherapy and secondary radiotherapy (prior to secondary radiotherapy, the patient achieved a PFS of nearly 12 months via the treatment with oral anlotinib combined with TS-1). Up to now, the progress of the disease is ceased. The oral administration of targeted therapy and chemotherapy are still in progress and the general condition of the patient is good. This suggests that patients with advanced pancreatic cancer may benefit from treatment with the anlotinib targeted therapy combined with TS-1 chemotherapy.

Holliday Cross-Recognition Protein HJURP: Association With the Tumor Microenvironment in Hepatocellular Carcinoma and With Patient Prognosis.

Background: Hepatocellular carcinoma is the most common type of primary liver cancer, and it is associated with poor prognosis. It often fails to respond to immunotherapy, highlighting the need to identify genes that are associated with the tumor microenvironment and may be good therapeutic targets. We and others have shown that the Holliday cross-recognition protein HJURP can promote the proliferation, migration, and invasion by hepatocellular carcinoma cells, and that HJURP overexpression is associated with poor survival. Here we explored the potential relationship between HJURP and the tumor microenvironment in hepatocellular carcinoma. Methods: We used the Immuno-Oncology-Biological-Research (IOBR) software package to analyze the potential roles of HJURP in the tumor microenvironment. Using single-cell RNA sequencing data, we identified the cell clusters expressing abundant HJURP, then linked some of these clusters to certain bioprocesses using Gene Set Enrichment Analysis (GSEA). We validated the differential expression of HJURP in tumor-infiltrating CD8+ T cells, sorted by flow cytometry into populations based on the expression level of PD-1. We used weighted gene co-expression network analysis (WGCNA) to identify immunity-related genes whose expression strongly correlated with that of HJURP. The function of these genes was validated based on enrichment in Gene Ontology (GO) terms, and they were used to establish a prognosis prediction model. Results: IOBR analysis suggested that HJURP is significantly related to the immunosuppressive tumor microenvironment and was significantly related to T cells, dendritic cells, and B cells. Based on single-cell RNA sequencing, HJURP was strongly expressed in T cells, erythrocytes, and B cells from normal liver tissues, as well as in CD8+ T cells, dendritic cells, and one cluster of hepatocytes in hepatocellular carcinoma tissues. Malignant hepatocytes strongly expressing HJURP were associated with the downregulation of immune bioprocesses. HJURP expression was significantly higher in CD8+ T cells strongly expressing PD-1 than in those expressing no or intermediate levels of PD1. WGCNA identified two module eigengenes (comprising 397 and 84 genes) related to the tumor microenvironment. We identified 24 hub genes and confirmed that they were related to immune regulation. A prognostic risk score model based on expression of HJURP, PPT1, PML, and CLEC7A showed moderate ability to predict survival. Conclusion: HJURP is associated with tumor-infiltrating immune cells, immune checkpoints, and immune suppression in hepatocellular carcinoma. HJURP-related genes involved in immune responses may be useful for predicting patient prognosis.

Comparative physiological and transcriptome analysis reveals the potential mechanism of selenium accumulation and tolerance to selenate toxicity of Broussonetia papyrifera.

Broussonetia papyrifera is an important fodder tree that is widely distributed in China. Enhancing the selenium (Se) content in B. papyrifera may help to improve the nutritional value of the feed. In this study, sodium selenite and selenate were foliar applied to investigate the mechanisms of Se tolerance and accumulation in B. papyrifera. The results showed that both Se forms significantly increased the total Se content, and the proportion of organic Se was significantly higher in the sodium selenite treatment than in the control. In addition, the soluble sugar, phenolic acid and flavonoid contents and antioxidant enzyme activities were increased by exogenous Se. The de novo RNA sequencing results showed that 644 and 1804 differentially expressed genes were identified in the selenite and selenate comparison groups, respectively. Pathway enrichment analysis demonstrated that 24 of the 108 pathways were significantly enriched, of which sulfur assimilation genes in the sodium selenite-treated groups were upregulated, whereas Se conjugation and transporter genes, such as SBP1, PCS, GSTs, ABCs and GPX, were significantly induced under selenate treatment. The hub genes identified by weighted-gene co-expression network analysis further confirmed that sulfur assimilation, conjugation and transporter genes might play a vital role in Se assimilation and tolerance. From this, a model of Se metabolism in B. papyrifera was proposed based on the above physiological and RNA sequencing data. This study is the first study to report that B. papyrifera has a strong ability to accumulate and tolerate exogenous Se, thereby providing a foundation for further characterization of the accumulation and tolerance mechanism of B. papyrifera. Our findings can provide technical support for producing Se-enriched fodder.

Homologous Recombination Pathway Alternation Predicts Prognosis of Colorectal Cancer With Chemotherapy.

Background: Chemotherapy is the basic treatment for colorectal cancer (CRC). However, colorectal cancer cells often develop resistance to chemotherapy drugs, leading to recurrence and poor prognosis. More and more studies have shown that the Homologous recombination (HR) pathway plays an important role in chemotherapy treatment for tumors. However, the relationship between HR pathway, chemotherapy sensitivity, and the prognosis of CRC patients is still unclear. Methods: We collected 35 samples of CRC patients after chemotherapy treatment from Guangxi Medical University Cancer Hospital, then collected mutation data and clinical prognosis data from the group. We also downloaded Mondaca-CRC, TCGA-CRC cohorts for chemotherapy treatment. Result: We found that HR mutant-type (HR-MUT) patients are less likely to experience tumor metastasis after receiving chemotherapy. Additionally, our univariate and multivariate cox regression models showed that HR-MUT can be used as an independent predictor of the prognosis of chemotherapy for CRC patients. The KM curve showed that patients with HR-MUT CRC had significantly prolonged overall survival (OS) time (log-rank p = 0.017; hazard ratio (HR) = 0.69). Compared to HR mutant-type (HR-WT), HR-MUT has a significantly lower IC50 value with several chemotherapeutic drugs. Pathway enrichment analysis further revealed that the HR-MUT displayed a significantly lower rate of DNA damage repair ability, tumor growth, metastasis activity, and tumor fatty acid metabolism activity than HR-WT, though its immune response activity was notably higher. Conclusion: These findings indicate that HR-MUT may be a relevant marker for CRC patients receiving chemotherapy, as it is closely related to improving OS time and reducing chemotherapy resistance.

Combined metabolome and transcriptome analysis reveal the mechanism of selenate influence on the growth and quality of cabbage (Brassica oleracea var. capitata L.).

Selenium is an essential trace element for human and animal health, and an appropriate amount of Se can promote the growth and development of plants. Cabbage is a popular cruciferous vegetable with a good ability to accumulate Se, and Se-enriched cabbage can be used as an important Se source for humans. However, the effects of Se-enriched cultivation and the Se accumulation mechanism in cabbage are still unclear. In this study, the effects of different concentrations (0, 0.1, 0.2, 0.4, 0.8, and 1.6 mmol/L) of selenate on cabbage growth and quality were explored. A low concentration of selenate (0.1 mmol/L) promoted growth and nutritional quality. The contents of total Se, S, selenocystine, and selenomethionine significantly increased following selenate application. Important secondary metabolites, namely glucosinolates, phenolic acids, and flavonoids, participate in the response to selenate in cabbage. Comparative transcriptome and metabolomics analysis revealed that SULTR2.2, SULTR3.1, APS, APK2, HMT, MMT, and NTR2 played important roles in Se absorption and conversion. Additionally, the SUR1, UGT74B1, and ST5b genes and cytochrome P450 family genes CYP83A1, CYP79A2, and CYP79F1 may be the crucial genes in the glucosinolates biosynthesis and regulation pathway. The PAL, 4CL, CAD, CHS3, FLS, and CYP73A5 genes were involved in flavonoid and phenolic acid accumulation under selenate treatment. These results reveal the internal relationships in the regulatory network of Se metabolism and secondary metabolite biosynthesis in cabbage and help further the understanding of the physiological and molecular mechanism of how Se biofortification affects cabbage quality, thereby providing genetic resources and a technical basis for the breeding and cultivation of Se-enriched cabbage with excellent nutritional quality.

Analysis of ß-blockers and ß2-agonists in environmental and biological samples by magnetic solid-phase extraction combined with high-performance liquid chromatography-tandem mass spectrometry.

ß-Blockers and ß2-agonists are commonly prescribed for therapeutic treatments and are also administered to livestock, leading to their presence in both environmental and biological samples. Hence, the development of sensitive, rapid, and reliable analytical methods for the determination of ß-blockers and ß2-agonists in environmental and biological samples is important. In this study, MIL-101(Cr)-NH2 &GO-coated SiO2 /Fe3 O4 magnetic particles were prepared as sorbents for magnetic solid-phase extraction and then combined with high-performance liquid chromatography-tandem mass spectrometry for the analysis of 20 ß-blockers and eight ß2-agonists. The experimental parameters of magnetic solid-phase extraction were studied in detail, and the optimal conditions were established. Under optimal conditions, the limits of detection were in the range of 0.002-0.007 µg/L with enrichment factors of 20.2-24.9. The developed method was successfully applied for the determination of 20 ß-blockers and eight ß2-agonists in river water, human urine, and freeze-dried pork liver powder. Bisoprolol and salbutamol were detected at concentrations of 2.78 mg/L in human urine and 11.5 µg/kg in freeze-dried pork liver powder.

Industrial Transformation and Urban Economic Efficiency Evolution: An Empirical Study of the Yangtze River Economic Belt.

Industrial transformation and high-quality urban development have become the core issues of urban-rural coordination and the leap forward in development in the new era. The research perspective of 'pattern-process-mechanism' is needed to reveal the spatiotemporal correlation characteristics of industrial transformation and urban economic efficiency evolution, and to expand its systematic, comprehensive and regional characteristics. Based on the geographical cognitive of local effects and spatial non-stationarity, we used a quantile regression model and a geographically weighted regression model to analyze the dynamic mechanism of industrial transformation and urban economic efficiency to explain the path characteristics of urban development and industrial transformation of the Yangtze River economic belt. The conclusions are as follows: (1) From 2000 to 2015, the average economic efficiency in the Yangtze River economic belt increased from 0.05 to 0.332, and the pattern gradually changed from spatial homogeneity to spatial mosaic; (2) From 2000 to 2015, the range and intensity of industrial transformation in the Yangtze River economic belt showed an increasing trend, while the speed of industrial transformation showed a downward trend, and the high-value unit of the three showed the characteristics of gradual homogenization; (3) From the perspective of the impact of industrial transformation on urban economic efficiency, the impact of the range and speed of industrial transformation on urban economic efficiency was gradually weakened, while the impact of the intensity of industrial transformation on urban economic efficiency was gradually strengthened, and the patterns of the three show the characteristics of a spatially inverted U-shaped distribution with high values in the middle reaches and low values in the upstream and downstream areas.

The Microglial membrane receptor TREM2 mediates exosome secretion to promote phagocytosis of amyloid-ß by microglia.

Considerable evidence links the microglial transmembrane receptor TREM2 to the progression of Alzheimer's disease through its involvement in Aß phagocytosis by microglia. While previous studies have mainly focused on the phagocytic regulation of microglia itself, the antigen presentation of microglial exosomes in the process of immunity has been less investigated. Here, we identified TREM2 expressed on the membrane of microglial exosomes and found that it controlled exosome secretion without affecting exosome size. Microglial exosomes bind to Aß in a TREM2-dependent manner, which changes the inflammatory environment around Aß and promotes microglia to phagocytose Aß. These findings delineate a novel exosome-mediated mechanism of microglial cell-Aß crosstalk that facilitates Aß clearance under either physiological or pathological conditions in the central nervous system.

Prognostic value of long non-coding RNA MALAT1 in hepatocellular carcinoma: A study based on multi-omics analysis and RT-PCR validation.

Background: This study aimed to explore the relationship between MALAT1 and the prognosis of patients with hepatocellular carcinoma (HCC). Methods: We constructed a MALAT1 protein-protein interaction network using the STRING database and a network of competing endogenous RNAs (ceRNAs) using the StarBase database. Using data from the GEPIA2 database, we studied the association between genes in these networks and survival of patients with HCC. The potential mechanisms underlying the relationship between MALAT1 and HCC prognosis were studied using combined data from RNA sequencing, DNA methylation, and somatic mutation data from The Cancer Genome Atlas (TCGA) liver cancer cohort. Tumor tissues and 19 paired adjacent non-tumor tissues (PANTs) from HCC patients who underwent radical resection were analyzed for MALAT1 mRNA levels using real-time PCR, and associations of MALAT1 expression with clinicopathological features or prognosis of patients were analyzed using log-rank test and Gehan-Breslow-Wilcoxon test. Results: Five interacting proteins and five target genes of MALAT1 in the ceRNA network significantly correlated with poor survival of patients with HCC (p < 0.05). High MALAT1 expression was associated with mutations in two genes leading to poor prognosis and may upregulate some prognostic risk genes through methylation. MALAT1 was significantly co-expressed with various signatures of genes involved in HCC progression, including the cell cycle, DNA damage repair, mismatch repair, homologous recombination, molecular cancer m6A, exosome, ferroptosis, infiltration of lymphocyte (p < 0.05). The expression of MALAT1 was markedly upregulated in HCC tissues compared with PANTs. In Kaplan-Meier analysis, patients with high MALAT1 expression had significantly shorter progression-free survival (PFS) (p = 0.033) and overall survival (OS) (p = 0.023) than those with low MALAT1 expression. Median PFS was 19.2 months for patients with high MALAT1 expression and 52.8 months for patients with low expression, while the corresponding median OS was 40.5 and 78.3 months. In subgroup analysis of patients with vascular invasion, cirrhosis, and HBsAg positive or AFP positive, MALAT1 overexpression was significantly associated with shorter PFS and OS. Models for predicting PFS and OS constructed based on MALAT1 expression and clinicopathological features had moderate predictive power, with areas under the receiver operating characteristic curves of 0.661-0.731. Additionally, MALAT1 expression level was significantly associated with liver cirrhosis, vascular invasion, and tumor capsular infiltration (p < 0.05 for all). Conclusion: MALAT1 is overexpressed in HCC, and higher expression is associated with worse prognosis. MALAT1 mRNA level may serve as a prognostic marker for patients with HCC after hepatectomy.