Effectiveness of Sensitization Campaigns in Reducing Leprosy-Related Stigma in Rural Togo: Protocol for a Mixed Methods Cluster Randomized Controlled Trial.

BACKGROUND: In the global strategy to eliminate leprosy, there remains a need for early case detection to successfully interrupt transmissions. Poor knowledge about leprosy and leprosy-related stigma are key drivers of delayed diagnosis and treatment. Sensitization campaigns to inform and increase awareness among the general population are an integral part of many national neglected tropical disease programs. Despite their importance, the effectiveness of such campaigns has not been rigorously studied in the West African context. A multilingual rural setting with low health literacy in this region presents challenges to the potential impact of sensitization campaigns. OBJECTIVE: The primary objective of this study is to assess the causal effect of common practice community sensitization campaigns on leprosy-related knowledge and stigma at the community level and among community health volunteers. Additionally, we will test the potential of novel educational audio tools in the 15 most prominent local languages to overcome literacy and language barriers and amplify sensitization campaigns. METHODS: We will conduct a cluster randomized controlled trial using a sequential mixed methods approach in 60 rural communities across all regions of Togo, West Africa. The study features 2 intervention arms and 1 control arm, with intervention and control assignments made at the community level through randomization. Communities in intervention arm 1 will receive a sensitization campaign in line with the current Togolese national neglected tropical disease program. Communities in intervention arm 2 will receive the same sensitization campaign along with educational audio tools distributed to community households. The control arm will receive no intervention before data collection. Quantitative outcome measures on knowledge and stigma will be collected from a random sample of 1200 individuals. Knowledge will be assessed using the 9-item standardized Knowledge, Attitudes, and Practices Questionnaire. Stigma will be measured using the 7-item Social Distance Scale and the 15-item Explanatory Model Interview Catalogue Community Stigma Scale. We will estimate intention-to-treat effects at the individual level, comparing the outcomes of the intervention and control arms. In an accompanying qualitative component, we will conduct in-depth interviews with community members, community health volunteers, and health care workers in both treatment arms and the control arm to explore intervention and stigma-related experiences. RESULTS: This paper describes and discusses the protocol for a mixed methods cluster randomized controlled trial. Data collection is planned to be completed in June 2024, with ongoing data analysis. The first results are expected to be submitted for publication by the end of 2024. CONCLUSIONS: This trial will be among the first to test the causal effectiveness of community-based sensitization campaigns and audio tools to increase knowledge and reduce leprosy-related stigma. As such, the results will inform health policy makers, decision-makers, and public health practitioners designing sensitization campaigns in rural multilingual settings. TRIAL REGISTRATION: German Clinical Trials Register DRKS00029355; https://drks.de/search/en/trial/DRKS00029355. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52106.

Integrating a Multiple Isotopologue Reaction-Monitoring Technique and LC-MS/MS for Quantitation of Small Molecules: Ten Mycotoxins in Cereals as an Example.

Accurate quantification of mycotoxin in cereals is crucial for ensuring food safety and human health. However, the preparation of traditional multisample external calibration curves (MSCCs) is labor-intensive and error-prone. Here, a multiple isotopologue reaction-monitoring (MIRM)-LC-MS/MS method for accurate quantitation of ten major mycotoxins in cereals was successfully developed and validated, where a novel one-sample multipoint calibration curve (OSCC) strategy is used instead of MSCCs. The OSCC can be established by examining the correlation between the calculated theoretical isotopic abundances and the measured abundance across various MIRM channels. In comparison to the MSCC, the OSCC strategy exhibits outstanding performance including superior selectivity, accuracy (78.4-108.6%), and precision (<12.5%). Furthermore, the proposed OSCC-MIRM-LC-MS/MS method was successfully applied to investigate mycotoxin contamination in cereal samples in China. Considering the advantages of simplified workflows and improved throughput, the OSCC-MIRM-LC-MS/MS methodology holds great promise for accurately quantifying chemical contaminants in foods.

Advancing High-Throughput MS-Based Protein Quantification: A Case Study on Quantifying 10 Major Food Allergens by LC-MS/MS Using a One-Sample Multipoint External Calibration Curve.

The LC-MS-based method has emerged as the preferred approach for quantifying food allergens. However, the preparation of a traditional calibration curve (MSCC) is labor-intensive and error-prone. Here, a sensitive and robust LC-MS/MS method for quantifying 10 major food allergens was developed and validated, where the one-sample multipoint external calibration curve (OSCC) was employed instead of MSCC. By employing the multiple isotopologue reaction monitoring (MIRM) technique with only one spiked level in the blank, OSCC can be effectively established. Results demonstrate that the proposed method exhibits excellent performance in selectivity, sensitivity, accuracy, and precision, comparable to that of the traditional MSCC. Additionally, this strategy allows for isotope sample dilution by monitoring the less abundant MIRM channel. Moreover, the developed method was successfully applied to investigate the contamination of 10 food allergens in commercial food products. With its high throughput and robustness, the MIRM-OSCC-LC-MS/MS methodology has many potential applications, especially in the MS-based protein quantification analysis.

Community-based interventions targeting multiple forms of malnutrition among adolescents in low-income and middle-income countries: protocol for a scoping review.

BACKGROUND: Adolescent malnutrition is a significant public health challenge in low-income and middle-income countries (LMICs), with long-term consequences for health and development. Community-based interventions have the potential to address multiple forms of malnutrition and improve the health outcomes of adolescents. However, there is a limited understanding of the content, implementation and effectiveness of these interventions. This scoping review aims to synthesise evidence on community-based interventions targeting multiple forms of malnutrition among adolescents in LMICs and describe their effects on nutrition and health. METHODS AND ANALYSIS: A comprehensive search strategy will be implemented in multiple databases including MEDLINE (through PubMed), Embase, CENTRAL (through Cochrane Library) and grey literature, covering the period from 1 January 2000 to 14 July 2023. We will follow the Participants, Concept and Context model to design the search strategy. The inclusion criteria encompass randomised controlled trials and quasi-experimental studies focusing on adolescents aged 10-19 years. Various types of interventions, such as micronutrient supplementation, nutrition education, feeding interventions, physical activity and community environment interventions, will be considered. Two reviewers will perform data extraction independently, and, where relevant, risk of bias assessment will be conducted using standard Cochrane risk-of-bias tools. We will follow the PRISMA Extension for Scoping Reviews checklist while reporting results. ETHICS AND DISSEMINATION: The scope of this scoping review is restricted to publicly accessible databases that do not require prior ethical approval for access. The findings of this review will be shared through publications in peer-reviewed journals, and presentations at international and regional conferences and stakeholder meetings in LMICs. SCOPING REVIEW REGISTRATION: The final protocol was registered prospectively with the Open Science Framework on 19 July 2023 (https://osf.io/t2d78).

Myelodysplastic syndrome with IgG4­related disease: A case report.

At present, to the best of our knowledge, there are only a few case reports of IgG4-related disease (IgG4-RD) involving myelodysplastic syndrome (MDS), yet the incidence of MDS and IgG4-RD is increasing in middle-aged and elderly people. The present study presents a case of MDS combined with IgG4-RD admitted to Zhejiang Provincial Hospital of Chinese Medicine in September 2022. The (66-year-old; male) patient was admitted to the hospital due to hematopenia with an elevated IgG4 index. The diagnosis of MDS combined with IgG4-RD was confirmed after various exams, including pathological examination. The condition of the patient improved after 3 weeks of hormone therapy, with a significant increase in complete blood count compared with the pre-treatment period. MDS is a malignant hematological disorder with a high risk of conversion to leukemia, and IgG4-RD is a systemic immune-mediated disease with a poor prognosis often associated with malignancy. The present study presents and reviews the literature to better understand the coexistence of these two diseases.

The role of type VI secretion system genes in antibiotic resistance and virulence in Acinetobacter baumannii clinical isolates.

Introduction: The type VI secretion system (T6SS) is a crucial virulence factor in the nosocomial pathogen Acinetobacter baumannii. However, its association with drug resistance is less well known. Notably, the roles that different T6SS components play in the process of antimicrobial resistance, as well as in virulence, have not been systematically revealed. Methods: The importance of three representative T6SS core genes involved in the drug resistance and virulence of A. baumannii, namely, tssB, tssD (hcp), and tssM was elucidated. Results: A higher ratio of the three core genes was detected in drug-resistant strains than in susceptible strains among our 114 A. baumannii clinical isolates. Upon deletion of tssB in AB795639, increased antimicrobial resistance to cefuroxime and ceftriaxone was observed, alongside reduced resistance to gentamicin. The ΔtssD mutant showed decreased resistance to ciprofloxacin, norfloxacin, ofloxacin, tetracycline, and doxycycline, but increased resistance to tobramycin and streptomycin. The tssM-lacking mutant showed an increased sensitivity to ofloxacin, polymyxin B, and furazolidone. In addition, a significant reduction in biofilm formation was observed only with the ΔtssM mutant. Moreover, the ΔtssM strain, followed by the ΔtssD mutant, showed decreased survival in human serum, with attenuated competition with Escherichia coli and impaired lethality in Galleria mellonella. Discussion: The above results suggest that T6SS plays an important role, participating in the antibiotic resistance of A. baumannii, especially in terms of intrinsic resistance. Meanwhile, tssM and tssD contribute to bacterial virulence to a greater degree, with tssM being associated with greater importance.

NLRP3 knockout in mice provided protection against Serratia marcescens-induced acute pneumonia by decreasing PD-L1 and PD-1 expression in macrophages.

Antibiotic-resistant Serratia marcescens (Sm) is known to cause bloodstream infections, pneumonia, etc. The nod-like receptor family, pyrin domain-containing 3 (NLRP3), has been implicated in various lung infections. Yet, its role in Sm-induced pneumonia was not well understood. In our study, we discovered that deletion of Nlrp3 in mice significantly improved Sm-induced survival rates, reduced bacterial loads in the lungs, bronchoalveolar lavage fluid (BALF), and bloodstream, and mitigated the severity of acute lung injury (ALI) compared to wild-type (WT) mice. Mechanistically, we observed that 24 h post-Sm infection, NLRP3 inflammasome activation occurred, leading to gasdermin D NH2-terminal (GSDMD-NT)-induced pyroptosis in macrophages and IL-1ß secretion. The NLRP3 or NLRP3 inflammasome influenced the expression PD-L1 and PD-1, as well as the count of PD-L1 or PD-1-expressing macrophages, alveolar macrophages, interstitial macrophages, PD-L1-expressing neutrophils, and the count of macrophage receptors with collagenous structure (MARCO)-expressing macrophages, particularly MARCO+ alveolar macrophages. The frequency of MARCO+ alveolar macrophages, PD-1 expression, particularly PD-1+ interstitial macrophages were negatively or positively correlated with the Sm load, respectively. Additionally, IL-1ß levels in BALF correlated with three features of acute lung injury: histologic score, protein concentration and neutrophil count in BALF. Consequently, our findings suggest that Nlrp3 deletion offers protection agaisnt acute Sm pneumonia in mice by inhibiting inflammasome activation and reducing Sm infection-induced PD-L1/PD-1 or MARCO expression, particularly in macrophages. This highlights potential therapeutic targets for Sm and other gram-negative bacteria-induced acute pneumonia.

Reducing the Depletion Region Width at the Anode Interface via a Highly Doped Conjugated Polyelectrolyte Composite for Efficient Organic Solar Cells.

In the realm of organic solar cells (OSCs), the width of the depletion region at the anode interface is a critical factor that adversely impacts the open-circuit voltage (Voc) and the power conversion efficiency (PCE). To address this challenge, a novel approach involving a conjugated polyelectrolyte (CPE)-based composite, PCP-2F-Li:POM, has been developed. This composite serves as a solution-processed hole transport layer (HTL), effectively minimizing the depletion region width in high-performance OSCs. The innovative aspect of PCP-2F-Li:POM lies in its "mutual doping" mechanism. Polyoxometalate (POM) is utilized as a dopant, facilitating the formation of p-doped CPE and n-doped POM within the composite. This results in a substantial increase in doping density, nearly 2 orders of magnitude higher than that observed in unmodified CPE. Consequently, the width of depletion region is markedly reduced, shrinking from 76.4 to 6.0 nm. This reduction plays a pivotal role in enhancing hole transport via the tunneling effect. The practical impact of this development is notable. It leads to an increase in Voc from 0.84 to 0.86 V, thereby contributing significantly to an impressive PCE of 18.04% in OSCs. Moreover, the compatibility of PCP-2F-Li:POM with large-area processing techniques underscores its potential as a viable HTL material for future practical applications. Additionally, its contribution to the enhanced long-term stability of OSCs further bolsters its suitability for practical applications.

Associations of Menstrual Cycle and Progesterone-to-Estradiol Ratio With Alcohol Consumption in Alcohol Use Disorder: A Sex-Separated Multicenter Longitudinal Study.

OBJECTIVE: Alcohol use disorder (AUD) constitutes a critical public health issue and has sex-specific characteristics. Initial evidence suggests that progesterone and estradiol might reduce or increase alcohol intake, respectively. However, there is a need for a better understanding of how the menstrual cycle in females and the ratio of progesterone to estradiol in females and males influence alcohol use patterns in individuals with AUD. METHODS: In this sex-separated multicenter longitudinal study, the authors analyzed 12-month data on real-life alcohol use (from 21,460 smartphone entries), menstrual cycle, and serum progesterone-to-estradiol ratios (from 667 blood samples at four individual study visits) in 74 naturally cycling females and 278 males with AUD between 2020 and 2022, using generalized and general linear mixed modeling. RESULTS: Menstrual cycle phases were significantly associated with binge drinking and progesterone-to-estradiol ratio. During the late luteal phase, females showed a lower predicted binge drinking probability of 13% and a higher predicted marginal mean of progesterone-to-estradiol ratio of 95 compared with during the menstrual, follicular, and ovulatory phases (binge drinking probability and odds ratios vs. late luteal phase, respectively: 17%, odds ratio=1.340, 95% CI=1.031, 1.742; 19%, odds ratio=1.523, 95% CI=1.190, 1.949; and 20%, odds ratio=1.683, 95% CI=1.285, 2.206; difference in progesterone-to-estradiol ratios, respectively: -61, 95% CI=-105.492, -16.095; -78, 95% CI=-119.322, -37.039; and -71, 95% CI=-114.568, -27.534). In males, a higher progesterone-to-estradiol ratio was related to lower probabilities of binge drinking and of any alcohol use, with a 10-unit increase in the hormone ratio resulting in odds ratios of 0.918 (95% CI=0.843, 0.999) and 0.914 (95% CI=0.845, 0.988), respectively. CONCLUSIONS: These ecologically valid findings suggest that high progesterone-to-estradiol ratios can have a protective effect against problematic alcohol use in females and males with AUD, highlighting the progesterone-to-estradiol ratio as a promising treatment target. Moreover, the results indicate that females with AUD may benefit from menstrual cycle phase-tailored treatments.

High-mind wandering correlates with high risk for problematic alcohol use in China and Germany.

Everyone experiences the natural ebb and flow of task-unrelated thoughts. Given how common the fluctuations in these thoughts are, surprisingly, we know very little about how they shape individuals' responses to alcohol use. Here, we investigated if mind wandering is associated with a risk of developing problematic alcohol use. We undertook an online survey among the general population in China (N = 1123) and Germany (N = 1018) from December 2021 to February 2022 and examined the subjective experience of mind wandering and problematic alcohol use through the Mind Wandering Questionnaire (MWQ) and the Alcohol Use Disorders Identification Test (AUDIT). We compared mind wandering and problematic alcohol use between two countries and investigated the association between MWQ scores with AUDIT scores. We found higher scores on the MWQ and a high percentage of problematic alcohol use (i.e., AUDIT score ≥ 8) in Germany (22.5%) as compared to in China (14.5%). Higher self-reported mind wandering was associated with higher AUDIT scores. AUDIT scores were increased mostly in male, elder, and high-mind wandering people. Our findings highlight that mind wandering and problematic alcohol use enhanced in Germany as compared to in China. Our study sheds light on the relationship between mind wandering and problematic alcohol use that may help to further investigate causal effects of interventions.

An integrated calibration strategy for the development and validation of an LC-MS/MS method for accurate quantification of egg allergens (Gal d 1-6) in foods.

Accurate determination of egg allergens in food is vital for allergen management and labeling. However, quantifying egg allergens with mass spectrometry poses challenges and lacks validation methods. Here, we developed and validated an LC-MS/MS method for quantifying egg allergens (Gal d 1-6) in foods. Sample extraction, enzymatic digestion, purification, proteins/peptides selection, and calibration curves were optimized. VMVLC[+57]NR (Gal d 1) and GTDVQAWIR (Gal d 5) exhibited outstanding sensitivity and stability, serving as quantitation markers for egg white and yolk. Using a matrix-matched calibration curve with allergen ingredients as calibrants and labeled peptides as standards, we achieved highly accurate quantitation. Validation involved spiking egg protein into egg-free foods, showing excellent sensitivity (LOQ: 1-5 mg/kg), accuracy (62.4 %-88.5 %), and reproducibility (intra-/inter-day precision: 3.5 %-14.2 %/8.2 %-14.6 %). Additionally, we successfully applied this method to commercial food analysis. These findings demonstrate optimal allergen selection, peptides, and calibration strategy are crucial parameters for food allergen quantification via MS-based methods.

Involuntary social isolation and alcohol consumption: an ecological momentary assessment in Germany amid the COVID-19 pandemic.

AIMS: Alcohol consumption often occurs in a social setting, which was affected by social distancing measures amid the coronavirus disease-2019 (COVID-19) pandemic. In this study, we examine how involuntary social isolation (i.e. comparing a no-lockdown stage with a lockdown stage) affects the association between loneliness, social activities, and drinking behavior. METHOD: We performed an ecological momentary assessment eight times per day for 7 days amid the COVID-19 pandemic in Germany. We recruited 280 participants and assessed their trait loneliness, daily state loneliness, social activities, and drinking behaviors. RESULTS: We found that a lockdown condition moderates the association between trait and daily state loneliness and alcohol consumption. During a lockdown stage, trait loneliness was positively associated, whereas state loneliness was negatively associated with alcohol consumption. During a no-lockdown stage, trait and state loneliness were both negatively associated with alcohol consumption. For both no-lockdown and lockdown stages, duration of social interaction, male gender, and weekends was positively associated with alcohol consumption. CONCLUSION: Our study suggests that an involuntary social isolation condition (i.e. a lockdown stage) changes how trait loneliness is associated with alcohol consumption.

Circ_0068087 knockdown attenuates high-glucose-induced human tubular epithelial cell injury in a microribonucleic acid/progestin and adipoQ receptor 3-dependent manner in diabetic nephropathy.

AIMS/INTRODUCTION: Previous studies have shown that circular ribonucleic acid mediates the occurrence of diabetic nephropathy. This study aimed to analyze the effects of circ_0068087 on high-glucose (HG)-induced human kidney 2 (HK2) cell dysfunction. MATERIALS AND METHODS: Circ_0068087, miR-580-3p, and progestin and adipoQ receptor 3 (PAQR3) expression were detected by quantitative reverse transcription polymerase chain reaction. Cell viability and proliferation were investigated by Cell Counting Kit-8 and EdU assays, respectively. The cell apoptotic rate was assessed by flow cytometry. Inflammatory response was assessed by enzyme-linked immunoassays. Oxidative stress was evaluated by a superoxide dismutase activity assay kit and lipid peroxidation malondialdehyde assay kit. Molecular interaction was identified by dual-luciferase reporter assay. RESULTS: Circ_0068087 and PAQR3 expression were significantly upregulated in diabetic nephropathy patients. HG treatment inhibited HK2 cell proliferation, but induced cell apoptosis, inflammation, oxidative stress and epithelial-mesenchymal transition by regulating circ_0068087. Circ_0068087 acted as a microribonucleic acid-580-3p (miR-580-3p) sponge, and miR-580-3p targeted PAQR3. Furthermore, circ_0068087 depletion repressed PAQR3 expression through miR-580-3p. MiR-580-3p inhibitors or PAQR3 introduction attenuated circ_0068087 silencing mediated-effects in HG-treated HK2 cells. CONCLUSION: Circ_0068087 promoted HG-induced HK2 cell injuries by the regulation of the miR-580-3p/PAQR3 pathway.

Inhibiting the NLRP3 Inflammasome with MCC950 Alleviates Neurological Impairment in the Brain of EAE Mice.

Multiple sclerosis (MS) is a chronic disease that is characterized by demyelination and neuronal damage. Experimental autoimmune encephalomyelitis (EAE) mice are used to model the disease progression of MS and mirror MS-like pathology. Previous researches have confirmed that inhibition of NLRP3 inflammasome significantly alleviated the severity of EAE mice and the demyelination of spinal cord, but its effect on neuronal damage and oligodendrocyte loss in the brain remains unclear. In this study, female C57BL/6 mice were immunized with MOG35-55 and PTX to establish experimental autoimmune encephalomyelitis (EAE) model. MCC950, a selective NLRP3 inflammasome inhibitor, was used to investigate the effect of NLRP3 inflammasome on the pathological changes and glial cell activation in the brain of EAE mice by immunohistochemistry. Our results demonstrated that MCC950 ameliorated the neuronal damage, demyelination, and oligodendrocyte loss in the brain of EAE mice. This protective effect of MCC950 may be attributed to its ability to suppress the activation of glial cells and prevents microglia polarization to M1 phenotype. Our work indicates that inhibition of NLRP3 inflammasome has the therapeutic effects of neuroprotection through immunomodulation and is a promising therapeutic strategy for MS.

Silicon fractionations in coastal wetland sediments: Implications for biogeochemical silicon cycling.

Coastal wetland sediment is important reservoir for silicon (Si), and plays an essential role in controlling its biogeochemical cycling. However, little is known about Si fractionations and the associated factors driving their transformations in coastal wetland sediments. In this study, we applied an optimized sequential Si extraction method to separate six sub-fractions of non-crystalline Si (Sinoncry) in sediments from two coastal wetlands, including Si in dissolved silicate (Sidis), Si in the adsorbed silicate (Siad), Si bound to organic matter (Siorg), Si occluded in pedogenic oxides and hydroxides (Siocc), Si in biogenic amorphous silica (Siba), and Si in pedogenic amorphous silica (Sipa). The results showed that the highest proportion of Si in the Sinoncry fraction was Siba (up to 6.6 % of total Si (Sitot)), followed by the Sipa (up to 1.8 % of Sitot). The smallest proportion of Si was found in the Sidis and Siad fractions with the sum of both being <0.1 % of the Sitot. We found a lower Siocc content (188 ± 96.1 mg kg-1) when compared to terrestrial soils. The Sidis was at the center of the inter-transformation among Si fractions, regulating the biogeochemical Si cycling of coastal wetland sediments. Redundancy analysis (RDA) combined with Pearson's correlations further showed that the basic biogenic elements (total organic carbon and total nitrogen), pH, and sediment salinity collectively controlled the Si fractionations in coastal wetland sediments. Our research optimizes sediment Si fractionation procedure and provides insights into the role of sedimentary Si fractions in controlling Si dynamics and knowledge for unraveling the biogeochemical Si cycling in coastal ecosystems.

CircTAOK1 regulates high glucose induced inflammation, oxidative stress, ECM accumulation, and apoptosis in diabetic nephropathy via targeting miR-142-3p/SOX6 axis.

BACKGROUND: Diabetic nephropathy (DN) is a complication caused by diabetes. Circular RNAs (circRNAs) are a kind of RNA with a closed circular structure, which has high stability and is involved in many disease-related processes. The mechanism of circRNA TAO kinase 1 (circTAOK1) in the pathogenesis and development of DN is unclear. METHODS: CircTAOK1, microRNA (miR)-142-3p, and sex-determining region Y-box transcription factor 6 (SOX6) mRNA levels were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR). Cell counting kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to analyze cell proliferation. Cell cycle distribution was detected by flow cytometry. Western blot assay was performed to test B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax), cleaved-caspase 3, and fibronectin (FN), collagen I (Col I), and collagen IV (Col IV) protein levels. ELISA assay was used to measure interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α) levels. The reactive oxygen species (ROS) and malondialdehyde (MDA) levels and the superoxide dismutase (SOD) activity were assessed by the corresponding kits. And the correlation between miR-142-3p and circTAOK1 or SOX6 was confirmed by dual luciferase reporter assay, RNA immunoprecipitation assay and RNA pull down assay. RESULTS: CircTAOK1 and SOX6 expression levels were up-regulated, while miR-142-3p expression was down-regulated in DN serum and HG-treated HK-2 cells. Knockdown of circTAOK1 could inhibit cell injury of HG-induced HK-2 cells. The inhibitory effect of circTAOK1 knockdown on HG-induced HK-2 cell injury was restored by miR-142-3p downregulation. CircTAOK1 acted as a sponge for miR-142-3p, and SOX6 was targeted by miR-142-3p. The overexpression of SOX6 could recover the effect of miR-142-3p overexpression on HG-induced HK-2 cell injury. CircTAOK1 regulated the expression of SOX6 by targeting miR-142-3p. CONCLUSION: CircTAOK1 knockdown inhibited HG-induced HK-2 cell damage in DN by the miR-142-3p/SOX6 axis.

Morphology and molecular phylogeny of Neolentinus in northern China.

Neolentinus is a significant genus, belonging to Gloeophyllaceae, with important economic and ecological values, which are parasites on decaying wood of broad-leaf or coniferous trees, and will cause brown rot. However, the taxonomic study is lagging behind to other groups of macrofungi, especially in China. In view of this, we conducted morphological and molecular phylogenetic studies on this genus. We have discovered new types of cheilocystidia and with extremely long lamellae in Neolentinus, and, thus proposed it as a new species-Neolentinus longifolius. At the same time, we clarified the distribution of Neolentinus cyathiformis in China and provided a detailed description. Moreover, we also described two common species, viz. Neolentinus lepideus and Neolentinus adhaerens. All the species are described based on the Chinese collections. The key to the reported species of Neolentinus from China is provided. And the phylogeny of Neolentinus from China is reconstructed based on DNA sequences of multiple loci including the internal transcribed spacer (ITS) regions, the large subunit nuclear ribosomal RNA gene (nLSU), and the translation elongation factor 1-α gene (tef-1α). In addition, full morphological descriptions, illustrations, color photographs, taxonomic notes, and all the available sequences of Neolentinus species are provided.

Urinary orosomucoid and retinol binding protein levels as early diagnostic markers for diabetic kidney Disease.

BACKGROUND: Diabetic kidney disease (DKD) is the most common microvascular complication of diabetes, which has been a major cause of end-stage renal failure. Diagnosing diabetic kidney disease is important to prevent long-term kidney damage and determine the prognosis of patients with diabetes. In this study, we investigated the clinical significance of combined detection of urine orosomucoid and retinol-binding protein for early diagnosis of diabetic kidney disease. METHODS: We recruited 72 newly diagnosed patients with type 2 diabetes and 34 healthy persons from August 2016 to July 2018 at the First Affiliated Hospital of Henan Polytechnic University (Jiaozuo Second People's Hospital). Using the Mogensen grading criteria, participants were classified as having diabetes or diabetic kidney disease, and healthy persons constituted the control group. Urine orosomucoid and retinol-binding protein levels were measured and correlated with other variables. RESULTS: With the aggravation of renal damage, the level of urinary mucoid protein gradually increased. Urinary retinol-binding protein and microalbumin levels were significantly higher in the diabetes group than in control and nephropathy groups. Orosomucoid and retinol-binding protein might be independent risk factors for diabetes and diabetic kidney disease. Urinary orosomucoid significantly correlated with retinol-binding protein and microalbumin levels in the diabetic kidney disease group. CONCLUSION: Elevated urine orosomucoid and retinol-binding protein levels can be detected in the early stages of type 2 diabetic kidney disease. Both of these markers are important for diabetic kidney disease detection and early treatment.

Eu-doped carbon quantum dot as a selective probe for visualizing and monitoring sulfite in biological systems.

The detection of SO3 2- in complex environments and its visualization at the cellular level are critical for understanding its role in biological processes. In this study, we developed an Eu-doped long-wavelength fluorescent carbon quantum dot (CD2) and investigated the detection mechanism, interference effects and cellular imaging applications of the fluorescent probe CD2. The results show that the addition of SO3 2- induces an electronic rearrangement that restores CD2 to its original structure, leading to a rapid increase in fluorescence intensity. Selectivity experiments showed that CD2 has excellent selectivity to SO3 2-, with minimal interference from common anions. In addition, CD2 shows good biocompatibility for cellular imaging applications, as evidenced by the high cell viability observed in HeLa cells. Using confocal microscopy, we detected a significant enhancement of red fluorescence in HeLa cells after addition of exogenous SO3 2-, demonstrating the potential of CD2 as a probe for monitoring cellular SO3 2- levels. These findings highlight the promise of CD2 as a selective SO3 2- detection probe in complex environments and its utility in cellular imaging studies. Further studies are necessary to fully exploit the potential of CD2 in various biological and biomedical applications.

HuR-induced circ_0082319 contributes to hepatocellular carcinoma by elevating PTK2 through miR-505-3p.

The aim of the present research is to explore the biological function and mechanism of circ_0082319 in HCC progression. Circ_0082319, microRNA-505-3p (miR-505-3p), protein tyrosine kinase 2 (PTK2), and human antigen R (HuR, also known as ELAVL1) level were detected by real-time quantitative polymerase chain reaction. Cell viability, proliferation, apoptosis, invasion, and angiogenesis were measured using (4-5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, and tube formation assays. Protein levels of c-Myc, MMP2, PTK2, and HuR were examined using western blot. The glycolysis levels were assessed using specific kits. Binding between miR-505-3p and circ_0082319 or PTK2 was predicted by Starbase and verified by a dual-luciferase reporter and RNA immunoprecipitation assays. The biological role of circ_0082319 on HCC tumor growth was examined using xenograft tumor model in vivo. Circ_0082319, PTK2, and HuR were highly expressed, and miR-505-3p was reduced in HCC samples and cell lines. Moreover, the knockdown of circ_0082319 might repress HCC cell proliferation, invasion, angiogenesis, and induce apoptosis in vitro. In mechanism, circ_0082319 served as a sponge of miR-505-3p to regulate PTK2 expression. HuR expedited circ_0082319 expression in HCC cells. HuR-mediated circ_0082319 might accelerate HCC cell proliferation, invasion, angiogenesis, and suppress apoptosis by the miR-505-3p/PTK2 axis, hinting at a promising therapeutic target for HCC treatment.