Glutathione­iron hybrid nanozyme-based colorimetric sensor for specific and stable detection of thiram pesticide on fruit juices.

Given the potential dangers of thiram to food safety, constructing a facile sensor is significantly critical. Herein, we presented a colorimetric sensor based on glutathione­iron hybrid (GSH-Fe) nanozyme for specific and stable detection of thiram. The GSH-Fe nanozyme exhibits good peroxidase-mimicking activity with comparable Michaelis constant (Km = 0.551 mM) to the natural enzyme. Thiram pesticides can specifically limit the catalytic activity of GSH-Fe nanozyme via surface passivation, causing the change of colorimetric signal. It is worth mentioning that the platform was used to prepare a portable hydrogel kit for rapid qualitative monitoring of thiram. Coupling with an image-processing algorithm, the colorimetric image of the hydrogel reactor is converted into the data information for accurate quantification of thiram with a detection limit of 0.3 µg mL-1. The sensing system has good selectivity and high stability, with recovery rates in fruit juice samples ranging from 92.4% to 106.9%.

The dePARylase NUDT16 promotes radiation resistance of cancer cells by blocking SETD3 for degradation via reversing its ADP-ribosylation.

Poly(ADP-ribosyl)ation (PARylation) is a critical posttranslational modification that plays a vital role in maintaining genomic stability via a variety of molecular mechanisms, including activation of replication stress and the DNA damage response. The nudix hydrolase NUDT16 was recently identified as a phosphodiesterase that is responsible for removing ADP-ribose units and that plays an important role in DNA repair. However, the roles of NUDT16 in coordinating replication stress and cell cycle progression remain elusive. Here, we report that SETD3, which is a member of the SET-domain containing protein (SETD) family, is a novel substrate for NUDT16, that its protein levels fluctuate during cell cycle progression, and that its stability is strictly regulated by NUDT16-mediated dePARylation. Moreover, our data indicated that the E3 ligase CHFR is responsible for the recognition and degradation of endogenous SETD3 in a PARP1-mediated PARylation-dependent manner. Mechanistically, we revealed that SETD3 associates with BRCA2 and promotes its recruitment to stalled replication fork and DNA damage sites upon replication stress or DNA double-strand breaks, respectively. Importantly, depletion of SETD3 in NUDT16-deficient cells did not further exacerbate DNA breaks or enhance the sensitivity of cancer cells to IR exposure, suggesting that the NUDT16-SETD3 pathway may play critical roles in the induction of tolerance to radiotherapy. Collectively, these data showed that NUDT16 functions as a key upstream regulator of SETD3 protein stability by reversing the ADP-ribosylation of SETD3, and NUDT16 participates in the resolution of replication stress and facilitates HR repair.

Rapid Initiation of Antiretroviral Therapy with Coformulated Bictegravir, Emtricitabine, Tenofovir Alafenamide Versus Efavirenz, Lamivudine and Tenofovir Disoproxil Fumarate in HIV-positive Men Who Have Sex with Men in China: Week 48 Results of the Multicenter, Randomized Clinical Trial.

BACKGROUND: Most international treatment guidelines recommend rapid initiation of antiretroviral therapy (ART) for people newly diagnosed with HIV-1 infection, but experiences with rapid ART initiation remain limited in China. We aimed to evaluate the efficacy and safety of efavirenz (400-mg) plus lamivudine and tenofovir disoproxil fumarate (EFV + 3TC + TDF) versus coformulated bictegravir, emtricitabine, tenofovir alafenamide (BIC/FTC/TAF) in rapid ART initiation among HIV-positive men who have sex with men (MSM). METHODS: This multicenter, open-label, randomized clinical trial enrolled MSM aged ≥18 years to start ART within 14 days of confirmed HIV diagnosis. The participants were randomly assigned in a 1:1 ratio to receive EFV(400-mg) + 3TC + TDF or BIC/FTC/TAF. The primary end point was viral suppression (<50 copies/ml) at 48 weeks per FDA Snapshot analysis. RESULTS: Between March 2021 and July 2022, 300 participants were enrolled; 154 were assigned to receive EFV + 3TC + TDF (EFV group) and 146 BIC/FTC/TAF (BIC group). At week 48, 118 (79.2%) and 140 (95.9%) participants in the EFV and BIC group, respectively, were retained in care with viral suppression; and 24 (16.1%) and 1 (0.7%) participant in the EFV and BIC group (p < 0.001), respectively, discontinued treatment due to adverse effects, death, or loss to follow-up. The median increase of CD4 count was 181 and 223 cells/µL (p = 0.020), respectively, for the EFV and BIC group, at week 48. The overall incidence of adverse effects was significantly higher for the EFV group (65.8% vs 37.7%, P < 0.001). CONCLUSION: BIC/FTC/TAF was more efficacious and safer than EFV(400-mg) + 3TC + TDF for rapid ART initiation among HIV-positive MSM in China.

Radiomics and deep learning models to differentiate lung adenosquamous carcinoma: A multicenter trial.

Adenosquamous carcinoma (ASC) is frequently misdiagnosed or overlooked in clinical practice due to its dual histological components and potential transformation from either adenocarcinoma (ADC) or squamous cell carcinoma (SCC). Our study aimed to differentiate ASC from ADC and SCC by incorporating features of enhanced CTs and clinical characteristics to build radiomics and deep learning models. The classification models were trained in Xiangya Hospital and validated in two other independent hospitals. The areas under the receiver operating characteristic curves (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were used to estimate the performance. The optimal three-class classification model achieved a maximum AUC of 0.89 and accuracy of 0.81 in external validation sets, AUC of 0.99 and accuracy of 0.99 in the internal test set. These findings highlight the efficacy of our models in differentiating ASC, providing a non-invasive, timely, and accurate diagnostic approach before and during the treatment.

Role of Proviral HIV-1 DNA Genotyping for People Living with HIV (PLWH) Who Had Low-Level Viremia While Receiving Antiretroviral Therapy.

Objective: To analyze the antiretroviral resistance in people living with HIV (PLWH) who developed low-level viremia (LLV) during antiretroviral therapy (ART) via sequencing of their HIV-1 proviral DNA and RNA and comparisons of their proviral DNA genotyping data with their past and synchronous RNA genotyping data. Patients and Methods: PLWH with LLV while receiving ART for 6 months or longer from January 2020 to September 2021 were included. HIV-1 proviral DNA and RNA were extracted from white-blood cells and concentrated plasma by ultracentrifugation, respectively, and HIV-1 pol gene fragments were amplified and sequenced. The concordance in the detection of resistance-associated mutations (RAMs) were examined between proviral DNA vs past RNA genotyping and proviral DNA vs synchronous RNA genotyping. Results: Of the 150 PLWH with LLV, 117 proviral DNA pol sequences detected in 105 PLWH were successfully amplified and RAMs were present in 27.6% and the rate of RAMs conferring low-level or greater resistance to antiretrovirals examined was 17.1%. Fifty-six and 57 PLWH had results of past and synchronous RNA genotyping, respectively, for comparisons with those of proviral DNA genotyping; and the concordance rates were 76.8% and 75.4%, respectively. However, proviral DNA genotyping lost than gained partial information on antiretroviral resistance compared with past or synchronous RNA genotyping. Conclusion: We found that the concordance between proviral DNA and past and synchronous RNA genotyping was moderate. Proviral DNA genotyping lost than gained more information on antiretroviral resistance compared with past or synchronous RNA genotyping. To optimize ART in PLWH with LLV, antiretroviral resistance profile should be interpreted in combination with proviral DNA and RNA genotyping and a comprehensive review of previous treatment history.

SARS-CoV-2 nsp13 Restricts Episomal DNA Transcription without Affecting Chromosomal DNA.

Nonstructural protein 13 (nsp13), the helicase of SARS-CoV-2, has been shown to possess multiple functions that are essential for viral replication, and is considered an attractive target for the development of novel antivirals. We were initially interested in the interplay between nsp13 and interferon (IFN) signaling, and found that nsp13 inhibited reporter signal in an IFN-ß promoter assay. Surprisingly, the ectopic expression of different components of the RIG-I/MDA5 pathway, which were used to stimulate IFN-ß promoter, was also mitigated by nsp13. However, endogenous expression of these genes was not affected by nsp13. Interestingly, nsp13 restricted the expression of foreign genes originating from plasmid transfection, but failed to inhibit them after chromosome integration. These data, together with results from a runoff transcription assay and RNA sequencing, suggested a specific inhibition of episomal but not chromosomal gene transcription by nsp13. By using different truncated and mutant forms of nsp13, we demonstrated that its NTPase and helicase activities contributed to the inhibition of episomal DNA transcription, and that this restriction required direct interaction with episomal DNA. Based on these findings, we developed an economical and convenient high-throughput drug screening method targeting nsp13. We evaluated the inhibitory effects of various compounds on nsp13 by the expression of reporter gene plasmid after co-transfection with nsp13. In conclusion, we found that nsp13 can specifically inhibit episomal DNA transcription and developed a high-throughput drug screening method targeting nsp13 to facilitate the development of new antiviral drugs. IMPORTANCE To combat COVID-19, we need to understand SARS-CoV-2 and develop effective antiviral drugs. In our study, we serendipitously found that SARS-CoV-2 nsp13 could suppress episomal DNA transcription without affecting chromosomal DNA. Detailed characterization revealed that nsp13 suppresses episomal gene expression through its NTPase and helicase functions following DNA binding. Furthermore, we developed a high-throughput drug screening system targeting SARS-CoV-2 nsp13. Compared to traditional SARS-CoV-2 drug screening methods, our system is more economical and convenient, facilitating the development of more potent and selective nsp13 inhibitors and enabling the discovery of new antiviral therapies.

Hepatitis B virus hijacks TSG101 to facilitate egress via multiple vesicle bodies.

Hepatitis B virus (HBV) chronically infects 296 million individuals and there is no cure. As an important step of viral life cycle, the mechanisms of HBV egress remain poorly elucidated. With proteomic approach to identify capsid protein (HBc) associated host factors and siRNA screen, we uncovered tumor susceptibility gene 101 (TSG101). Knockdown of TSG101 in HBV-producing cells, HBV-infected cells and HBV transgenic mice suppressed HBV release. Co-immunoprecipitation and site mutagenesis revealed that VFND motif in TSG101 and Lys-96 ubiquitination in HBc were essential for TSG101-HBc interaction. In vitro ubiquitination experiment demonstrated that UbcH6 and NEDD4 were potential E2 ubiquitin-conjugating enzyme and E3 ligase that catalyzed HBc ubiquitination, respectively. PPAY motif in HBc and Cys-867 in NEDD4 were required for HBc ubiquitination, TSG101-HBc interaction and HBV egress. Transmission electron microscopy confirmed that TSG101 or NEDD4 knockdown reduces HBV particles count in multivesicular bodies (MVBs). Our work indicates that TSG101 recognition for NEDD4 ubiquitylated HBc is critical for MVBs mediated HBV egress.

Effects of green tea on lipid profile in overweight and obese women.

The effect of green tea administration on serum lipids' concentrations remains unclear as various investigations, which have explored this topic, have produced conflicting results. Gender might be one of the factors influencing the impact of green tea on the lipid profile. Hence, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of green tea intake on the lipid profile in overweight and obese women. We searched five databases (Web of Science, SCOPUS, Embase, PubMed/Medline, and Google Scholar) using a combination of MeSH and non-MeSH terms. Results were expressed as weighted mean differences (WMDs) and 95% confidence intervals (CIs) and synthesized with a random-effects model. In total, 15 eligible RCTs with 16 arms (1818 participants) were included in the meta-analysis. The combined effect size revealed a significant reduction in total cholesterol (TC) (WMD: -4.45 mg/dl, 95% CI: -6.63, -2.27, P<0.001) and low-density lipoprotein cholesterol (LDL-C) (WMD: -4.49 mg/dl, 95% CI: -7.50 to -1.47, P=0.003) concentrations following green tea supplementation in overweight and/or obese women. In addition, a more pronounced reduction of triglyceride (TG) levels occurred when the baseline TG value was ≥150 mg/dL (WMD: -24.45 mg/dL, 95% CI: -40.63 to -8.26, P=0.003). Moreover, a significant decrease in TG concentrations occurred in RCTs conducted on overweight subjects (BMI: 25-29.99 kg/m2) (WMD: -5.88 mg/dl, 95% CI: -10.76 to -0.99, P=0.01). In the subgroup analyses based on the study population, a notable increase in high-density lipoprotein cholesterol (HDL-C) values was observed in obese individuals (>30 kg/m2) (WMD: 2.63 mg/dl, 95% CI: 0.10 to 5.16, P=0.041). Consumption of green tea causes a reduction in LDL-C and TC concentrations in overweight and obese women. The decline in TG levels was notable particularly in overweight patients with hypertriglyceridemia at baseline. In addition, a significant increase in HDL-C was detected in obese subjects following intake of green tea.

Rapidly Inhibiting the Inflammatory Cytokine Storms and Restoring Cellular Homeostasis to Alleviate Sepsis by Blocking Pyroptosis and Mitochondrial Apoptosis Pathways.

Pyroptosis, systemic inflammation, and mitochondrial apoptosis are the three primary contributors to sepsis's multiple organ failure, the ultimate cause of high clinical mortality. Currently, the drugs under development only target a single pathogenesis, which is obviously insufficient. In this study, an acid-responsive hollow mesoporous polydopamine (HMPDA) nanocarrier that is highly capable of carrying both the hydrophilic drug NAD+ and the hydrophobic drug BAPTA-AM, with its outer layer being sealed by the inflammatory targeting peptide PEG-LSA, is developed. Once targeted to the region of inflammation, HMPDA begins depolymerization, releasing the drugs NAD+ and BAPTA-AM. Depletion of polydopamine on excessive reactive oxygen species production, promotion of ATP production and anti-inflammation by NAD+ replenishment, and chelation of BAPTA (generated by BA-AM hydrolysis) on overloaded Ca2+ can comprehensively block the three stages of sepsis, i.e., precisely inhibit the activation of pyroptosis pathway (NF-κB-NLRP3-ASC-Casp-1), inflammation pathway (IL-1ß, IL-6, and TNF-α), and mitochondrial apoptosis pathway (Bcl-2/Bax-Cyt-C-Casp-9-Casp-3), thereby restoring intracellular homeostasis, saving the cells in a state of "critical survival," further reducing LPS-induced systemic inflammation, finally restoring the organ functions. In conclusion, the synthesis of this agent provides a simple and effective synergistic drug delivery nanosystem, which demonstrates significant therapeutic potential in a model of LPS-induced sepsis.

Proteomics Analysis of Genetic Liability of Abdominal Aortic Aneurysm Identifies Plasma Neogenin and Kit Ligand: The ARIC Study.

BACKGROUND: Genome-wide association studies have reported 23 gene loci related to abdominal aortic aneurysm (AAA)-a potentially lethal condition characterized by a weakened dilated vessel wall. This study aimed to identify proteomic signatures and pathways related to these risk loci to better characterize AAA genetic susceptibility. METHODS: Plasma concentrations of 4870 proteins were determined using a DNA aptamer-based array. Linear regression analysis estimated the associations between the 23 risk alleles and plasma protein levels with adjustments for potential confounders in a race-stratified analysis of 1671 Black and 7241 White participants. Significant proteins were then evaluated for their prediction of clinical AAA (454 AAA events in 11 064 individuals), and those significantly associated with AAA were further interrogated using Mendelian randomization analysis. RESULTS: Risk variants proximal to PSRC1-CELSR2-SORT1, PCIF1-ZNF335-MMP9, RP11-136O12.2/TRIB1, ZNF259/APOA5, IL6R, PCSK9, LPA, and APOE were associated with 118 plasma proteins in Whites and 59 were replicated in Black participants. Novel associations with clinical AAA incidence were observed for kit ligand (HR, 0.59 [95% CI, 0.42-0.82] for top versus first quintiles) and neogenin (HR, 0.64 [95% CI, 0.46-0.88]) over a median 21.2-year follow-up; neogenin was also associated with ultrasound-detected asymptomatic AAA (N=4295; 57 asymptomatic AAA cases). Mendelian randomization inverse variance weighted estimates suggested that AAA risk is promoted by lower levels of kit ligand (OR per SD=0.67; P=1.4×10-5) and neogenin (OR per SD=0.50; P=0.03). CONCLUSIONS: Low levels of neogenin and kit ligand may be novel risk factors for AAA development in potentially causal pathways. These findings provide insights and potential targets to reduce AAA susceptibility.

Limited disassembly of cytoplasmic hepatitis B virus nucleocapsids restricts viral infection in murine hepatic cells.

BACKGROUND AND AIMS: Murine hepatic cells cannot support hepatitis B virus (HBV) infection even with supplemental expression of viral receptor, human sodium taurocholate cotransporting polypeptide (hNTCP). However, the specific restricted step remains elusive. In this study, we aimed to dissect HBV infection process in murine hepatic cells. APPROACH AND RESULTS: Cells expressing hNTCP were inoculated with HBV or hepatitis delta virus (HDV). HBV pregenomic RNA (pgRNA), covalently closed circular DNA (cccDNA), and different relaxed circular DNA (rcDNA) intermediates were produced in vitro . The repair process from rcDNA to cccDNA was assayed by in vitro repair experiments and in mouse with hydrodynamic injection. Southern blotting and in situ hybridization were used to detect HBV DNA. HBV, but not its satellite virus HDV, was restricted from productive infection in murine hepatic cells expressing hNTCP. Transfection of HBV pgRNA could establish HBV replication in human, but not in murine, hepatic cells. HBV replication-competent plasmid, cccDNA, and recombinant cccDNA could support HBV transcription in murine hepatic cells. Different rcDNA intermediates could be repaired to form cccDNA both in vitro and in vivo . In addition, rcDNA could be detected in the nucleus of murine hepatic cells, but cccDNA could not be formed. Interestingly, nuclease sensitivity assay showed that the protein-linked rcDNA isolated from cytoplasm was completely nuclease resistant in murine, but not in human, hepatic cells. CONCLUSIONS: Our results imply that the disassembly of cytoplasmic HBV nucleocapsids is restricted in murine hepatic cells. Overcoming this limitation may help to establish an HBV infection mouse model.

TRPM4 gene variation associated with climatic conditions in Chinese cattle.

The transient receptor potential (TRP) superfamily has been reported to play an important role in heat tolerance pathways. Based on the Bovine Genome Variation Database and Selective Signatures, a missense mutation (NC_037345.1: c.2237A > G: p. His746Arg) (rs209689836) was identified in the transient receptor potential cation channel subfamily M member 4 (TRPM4) gene, a member of the TRP family, corresponding to heat tolerance. Here, we explored the prevalence of this variant in 19 native Chinese cattle (comprised of 404 individuals) to determine its possible association with heat tolerance in Chinese cattle by using PCR and DNA sequencing. The distribution of alleles of NC_037345.1: c.2237A > G: p. His746Arg displays significant geographical differences across native Chinese cattle breeds, consistent with the distribution of indicine and taurine cattle in China. Additionally, the association analysis indicated that the G allele was significantly associated with mean annual temperature (T), relative humidity (RH) and temperature humidity index (THI) (p < .05), suggesting that cattle carrying allele G were distributed in regions with higher T, RH, and THI. In conclusion, our results suggested that the mutation of the TRPM4 gene in Chinese cattle might be a candidate locus associated with heat tolerance.

Effects of Biofuel Crop Switchgrass (Panicum virgatum) Cultivation on Soil Carbon Sequestration and Greenhouse Gas Emissions: A Review.

Under the macroenvironmental background of global warming, all countries are working to limit climate change. Internationally, biofuel plants are considered to have great potential in carbon neutralization. Several countries have begun using biofuel crops as energy sources to neutralize carbon emissions. Switchgrass (Panicum virgatum) is considered a resource-efficient low-input crop that produces bioenergy. In this paper, we reviewed the effects of switchgrass cultivation on carbon sequestration and greenhouse gas (GHG) emissions. Moreover, the future application and research of switchgrass are discussed and prospected. Switchgrass has huge aboveground and underground biomass, manifesting its huge carbon sequestration potential. The net change of soil surface 30 cm soil organic carbon in 15 years is predicted to be 6.49 Mg ha-1, significantly higher than that of other crops. In addition, its net ecosystem CO2 exchange is about -485 to -118 g C m-2 yr-1, which greatly affects the annual CO2 flux of the cultivation environment. Nitrogen (N) fertilizer is the main source of N2O emission in the switchgrass field. Nitrogen addition increases the yield of switchgrass and also increases the N2O flux of switchgrass soil. It is necessary to formulate the most appropriate N fertilizer application strategy. CH4 emissions are also an important indicator of carbon debt. The effects of switchgrass cultivation on CH4 emissions may be significant but are often ignored. Future studies on GHG emissions by switchgrass should also focus on CH4. In conclusion, as a biofuel crop, switchgrass can well balance the effects of climate change. It is necessary to conduct studies of switchgrass globally with the long-term dimension of climate change effects.

Advances and challenges in cataloging the human gut virome.

The human gut virome, which is often referred to as the "dark matter" of the gut microbiome, remains understudied. A better understanding of the composition and variations of the gut virome across populations is critical for exploring its impact on diseases and health. A series of advances in the characterization of human gut virome have unveiled high genetic diversity and various functional potentials of gut viruses. Here, we summarize the recently available human gut virome databases and discuss their features, procedures, and challenges with the intention to provide a reference to researchers to use while choosing a profiling database. We also propose a "best practice" for cataloging the viral population.

The Impact of Digital Economy on the Economic Growth and the Development Strategies in the post-COVID-19 Era: Evidence From Countries Along the "Belt and Road".

The digital economy is considered as an effective measure to mitigate the negative economic impact of the Corona Virus Disease 2019 (COVID-19) epidemic. However, few studies evaluated the role of digital economy on the economic growth of countries along the "Belt and Road" and the impact of COVID-19 on their digital industries. This study constructed a comprehensive evaluation index system and applied a panel data regression model to empirically analyze the impact of digital economy on the economic growth of countries along the "Belt and Road" before COVID-19. Then, a Global Trade Analysis Project (GTAP) model was used to examine the impact of COVID-19 on their digital industries and trade pattern. Our results show that although there is an obvious regional imbalance in the digital economy development in countries along the "Belt and Road", the digital economy has a significantly positive effect on their economic growth. The main impact mechanism is through promoting industrial structure upgrading, the total employment and restructuring of employment. Furthermore, COVID-19 has generally boosted the demand for the digital industries, and the impact from the demand side is much larger than that from the supply side. Specifically, the digital industries in Armenia, Israel, Latvia and Estonia have shown great growth potential during the epidemic. On the contrast, COVID-19 has brought adverse impacts to the digital industries in Ukraine, Egypt, Turkey, and the Philippines. The development strategies are proposed to bridge the "digital divide" of countries along the "Belt and Road," and to strengthen the driving effect of the digital economy on industrial upgrading, employment and trade in the post-COVID-19 era.

Embedding Proteins within Spatially Controlled Hierarchical Nanoarchitectures for Ultrasensitive Immunoassay.

Modulating the precise self-assembly of functional biomacromolecules is a critical challenge in biotechnology. Herein, functional biomacromolecule-assembled hierarchical hybrid nanoarchitectures in a spatially controlled fashion are synthesized, achieving the biorecognition behavior and signal amplification in the immunoassay simultaneously. Biomacromolecules with sequential assembly on the scaffold through the biomineralization process show significantly enhanced stability, bioactivity, and utilization efficiency, allowing tuning of their functions by modifying their size and composition. The hierarchically hybrid nanoarchitectures show great potential in construction of ultrasensitive immunoassay platforms, achieving a three order-of-magnitude increase in sensitivity. Notably, the well-designed HRP@Ab2 nanoarchitectures allow for optical immunoassays with a detection range from picogram mL-1 to microgram mL-1 on demand, providing great promise for quantitative analysis of both low-abundance and high-residue targets for biomedical applications.

Loss to follow-up among human immunodeficiency virus-positive postpartum women and its predictive factors: A retrospective study.

OBJECTIVES: Antiretroviral treatment (ART) is essential in preventing mother-to-child transmission of human immunodeficiency virus (HIV), and postpartum discontinuation of ART is associated with adverse outcomes. This study identified factors associated with postpartum follow-up of HIV-positive women. METHODS: This was a retrospective cohort study of 170 HIV-infected pregnant women who received regular obstetric examination and delivered successfully in Beijing between 2003 and 2020.The women's sociodemographic, clinical, treatment, obstetric, and gestational characteristics were analyzed. Cox proportional hazards models were used to estimate adjusted hazard ratios (AHRs) of loss to follow-up between levels of confounders. RESULTS: In the multivariable Cox proportional hazard models, women with a longer time from HIV diagnosis to delivery per year had a 1.4-timeshigher risk (AHR = 1.433, 95% CI: 0.897-2.229) and a higher rate of loss to follow-up than the other women. Perinatal health care (AHR = 0.003,95% CI: 0.000-0.105) and gestational age above 37 weeks at delivery (AHR = 0.294, 95% CI: 0.005-15.818) were associated with a longer follow-up of postpartum HIV-positive women, when compared to women who did not receive perinatal healthcare and who delivered before 37 weeks of gestation, respectively. CONCLUSIONS: The longer time from HIV diagnosis to delivery, access to perinatal care, and full-term gestation at delivery improved postpartum ART adherence and follow-up among HIV-positive women. Early initiation of ART, integration of adult ART into prevention of mother-to-child transmission, combination ART with maternal healthcare, and enhanced pregnancy care will improve ART adherence among HIV-positive women after delivery.

N6-methyladenosine modification participates in neoplastic immunoregulation and tumorigenesis.

This review aims to provide insight into the role of N6-methyladenosine (m6A) modification in neoplastic immunity and subsequent tumorigenesis. m6A modification, which is catalyzed by methyltransferases, demethylases and reader proteins, has emerged as a widespread regulatory mechanism that controls immune-related gene expression and immune reactions during tumorigenesis. Aberrant m6A modification changes the neoplastic immune response in multiple cancers by regulating immune cell infiltration, tumor-promoting inflammation, immunosuppression, immune surveillance, and antitumor immune responses. m6A modification affects immune cell recruitment and cancer-promoting inflammation in hepatocellular carcinoma (HCC) to alter the progression of HCC. m6A modification has been implicated in the infiltration of immune cells and the activation of immune pathways, changing the proliferation and metastasis of gastric cancer. Immune surveillance and the antitumor immune response in breast cancer were enhanced via m6A modification, which inhibited tumor proliferation. m6A modification participates in neoplastic immunoregulation to influence tumor progression.

Bioinspired laccase-mimicking catalyst for on-site monitoring of thiram in paper-based colorimetric platform.

A long-standing goal has been to create artificial enzymes with natural enzyme-like catalytic activity. Herein, a laccase-mimicking catalyst (GSH-Cu) is designed by simulating the copper active sites and spatial amino acid microenvironment of natural enzymes. In particular, the engineered GSH-Cu shows a catalytic function that conforms to Michaelis-Menten kinetics of natural laccase. The high catalytic activity of GSH-Cu can be easily inhibited by thiram through surface passivation to produce copper nanoparticles. We demonstrate that the developed GSH-Cu with high stability and recyclability can be used to fabricate effective colorimetric sensor for sensitive detection of thiram. The resulting absorption intensity can be employed to quantify thiram in the range of 2.5-250 ng mL-1, which meets the detection requirement in fruit. Bestowed with the feasibility analysis of colorimetric output, a portable platform is designed by integrating GSH-Cu based test paper with a conventional smartphone for conveniently on-site quantified thiram. The proposed strategy about engineering enzyme-mimicking catalysts with excellent catalytic performance will open avenues for boosting the sensing application.

Expression of Programmed Death Ligand-2 is associated with Prognosis in Nasopharyngeal Carcinoma Microenviroment.

Background: Although immune checkpoint inhibitors have opened a new mode of treatment for solid tumors, their efficacy in nasopharyngeal carcinoma (NPC) needs to be further investigated. Inhibitors of the PD-1/PD-L1 immune checkpoint are one of the hot topics in tumor immunotherapy. Programmed death ligand-2 (PD-L2) is a less studied ligand of PD-1 and has not yet been fully explored, especially in NPC. Understanding the clinical significance of PD-L2 expression, together with immune cell infiltration, might provide clues for biomarker screening in NPC immunotherapy. This study aimed to evaluate the role of PD-L2 as a prognostic factor for NPC patients as well as its role in immune regulation. Methods: Immunohistochemistry (IHC) was performed on a tissue microarray including 557 NPC specimens using PD-L2 antibody. The immune cell markers CD4, FOXP3 and CD68 were also stained and quantified. The expression of PD-L2 exhibited different spatial patterns among NPC tumor and stromal tissues. Results: A total of 90.8% of the cases showed membranous PD-L2 expression in tumors, and 80.8% showed membranous PD-L2 expression in stromal tissue. High stromal expression of PD-L2 predicted favorable overall and disease-free survival of NPC patients and was negatively correlated with tumor size, recurrence or metastasis and clinical stage. In contrast, high tumor abundance of PD-L2 correlated with poor disease-free survival, but had no obvious correlation with clinicopathological parameters. Multivariate analysis indicated that stromal PD-L2 was an independent and favorable prognostic factor. Furthermore, we found a positive correlation between stromal PD-L2 expression and the infiltration of CD68+ macrophages and CD4+Foxp3+ Treg cells in NPC stromal tissues (Pearson correlation=0.181 and 0.098, respectively). Conclusions: Our results suggest that different PD-L2 expression patterns have distinct predictive values. PD-L2 expressed on stromal cells might play a role in the regulation of NPC progression, and involve in immune activation in the tissue microenvironment and have an independent good prognosis for NPC patients.