Collective effects of rising average temperatures and heat events on oviparous embryos.

Survival of the immobile embryo in response to rising temperature is important to determine a species' vulnerability to climate change. However, the collective effects of 2 key thermal characteristics associated with climate change (i.e., rising average temperature and acute heat events) on embryonic survival remain largely unexplored. We used empirical measurements and niche modeling to investigate how chronic and acute heat stress independently and collectively influence the embryonic survival of lizards across latitudes. We collected and bred lizards from 5 latitudes and incubated their eggs across a range of temperatures to quantify population-specific responses to chronic and acute heat stress. Using an embryonic development model parameterized with measured embryonic heat tolerances, we further identified a collective impact of embryonic chronic and acute heat tolerances on embryonic survival. We also incorporated embryonic chronic and acute heat tolerance in hybrid species distribution models to determine species' range shifts under climate change. Embryos' tolerance of chronic heat (T-chronic) remained consistent across latitudes, whereas their tolerance of acute heat (T-acute) was higher at high latitudes than at low latitudes. Tolerance of acute heat exerted a more pronounced influence than tolerance of chronic heat. In species distribution models, climate change led to the most significant habitat loss for each population and species in its low-latitude distribution. Consequently, habitat for populations across all latitudes will shift toward high latitudes. Our study also highlights the importance of considering embryonic survival under chronic and acute heat stresses to predict species' vulnerability to climate change.

Efectos colectivos del aumento de las temperaturas promedio y los eventos de calor en embriones ovíparos Resumen La supervivencia de los embriones inmóviles en respuesta al incremento de temperatura es importante para determinar la vulnerabilidad de las especies al cambio climático. Sin embargo, los efectos colectivos de dos características térmicas claves asociadas con el cambio climático (i. e., aumento de temperatura promedio y eventos de calor agudo) sobre la supervivencia embrionaria permanecen en gran parte inexplorados. Utilizamos mediciones empíricas y modelos de nicho para investigar cómo el estrés térmico crónico y agudo influye de forma independiente y colectiva en la supervivencia embrionaria de los lagartos en todas las latitudes. Recolectamos y criamos lagartos de cinco latitudes e incubamos sus huevos en un rango de temperaturas para cuantificar las respuestas específicas de la población al estrés por calor crónico y agudo. Posteriormente, mediante un modelo de desarrollo embrionario parametrizado con mediciones de tolerancia embrionaria al calor, identificamos un impacto colectivo de las tolerancias embrionarias al calor agudo y crónico en la supervivencia embrionaria. También incorporamos la tolerancia embrionaria crónica y aguda al calor en modelos de distribución de especies híbridas para determinar los cambios de distribución de las especies bajo el cambio climático. La tolerancia embrionaria al calor crónico (T­crónico) permaneció constante, mientras que la tolerancia al calor agudo (T­agudo) fue mayor en latitudes altas que en latitudes bajas. La tolerancia al calor agudo ejerció una influencia más pronunciada que la tolerancia al calor crónico. En los modelos de distribución de especies, el cambio climático provocó la pérdida de hábitat más significativa para cada población y especie en su distribución de latitudes bajas. En consecuencia, el hábitat para poblaciones en todas las latitudes se desplazará a latitudes altas. Nuestro estudio también resalta la importancia de considerar la supervivencia embrionaria bajo estrés térmico crónico y agudo para predecir la vulnerabilidad de las especies al cambio climático.

Detoxifying bacterial genes for deoxynivalenol epimerization confer durable resistance to Fusarium head blight in wheat.

Fusarium head blight (FHB) and the presence of mycotoxin deoxynivalenol (DON) pose serious threats to wheat production and food safety worldwide. DON, as a virulence factor, is crucial for the spread of FHB pathogens on plants. However, germplasm resources that are naturally resistant to DON and DON-producing FHB pathogens are inadequate in plants. Here, detoxifying bacteria genes responsible for DON epimerization were used to enhance the resistance of wheat to mycotoxin DON and FHB pathogens. We characterized the complete pathway and molecular basis leading to the thorough detoxification of DON via epimerization through two sequential reactions in the detoxifying bacterium Devosia sp. D6-9. Epimerization efficiently eliminates the phytotoxicity of DON and neutralizes the effects of DON as a virulence factor. Notably, co-expressing of the genes encoding quinoprotein dehydrogenase (QDDH) for DON oxidation in the first reaction step, and aldo-keto reductase AKR13B2 for 3-keto-DON reduction in the second reaction step significantly reduced the accumulation of DON as virulence factor in wheat after the infection of pathogenic Fusarium, and accordingly conferred increased disease resistance to FHB by restricting the spread of pathogenic Fusarium in the transgenic plants. Stable and improved resistance was observed in greenhouse and field conditions over multiple generations. This successful approach presents a promising avenue for enhancing FHB resistance in crops and reducing mycotoxin contents in grains through detoxification of the virulence factor DON by exogenous resistance genes from microbes.

The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci.

Backgrounds: Glioma is a highly malignant brain tumor with a grim prognosis. Genetic factors play a role in glioma development. While some susceptibility loci associated with glioma have been identified, the risk loci associated with prognosis have received less attention. This study aims to identify risk loci associated with glioma prognosis and establish a prognostic prediction model for glioma patients in the Chinese Han population. Methods: A genome-wide association study (GWAS) was conducted to identify risk loci in 484 adult patients with glioma. Cox regression analysis was performed to assess the association between GWAS-risk loci and overall survival as well as progression-free survival in glioma. The prognostic model was constructed using LASSO Cox regression analysis and multivariate Cox regression analysis. The nomogram model was constructed based on the single nucleotide polymorphism (SNP) classifier and clinical indicators, enabling the prediction of survival rates at 1-year, 2-year, and 3-year intervals. Additionally, the receiver operator characteristic (ROC) curve was employed to evaluate the prediction value of the nomogram. Finally, functional enrichment and tumor-infiltrating immune analyses were conducted to examine the biological functions of the associated genes. Results: Our study found suggestive evidence that a total of 57 SNPs were correlated with glioma prognosis (p < 5 × 10-5). Subsequently, we identified 25 SNPs with the most significant impact on glioma prognosis and developed a prognostic model based on these SNPs. The 25 SNP-based classifier and clinical factors (including age, gender, surgery, and chemotherapy) were identified as independent prognostic risk factors. Subsequently, we constructed a prognostic nomogram based on independent prognostic factors to predict individualized survival. ROC analyses further showed that the prediction accuracy of the nomogram (AUC = 0.956) comprising the 25 SNP-based classifier and clinical factors was significantly superior to that of each individual variable. Conclusion: We identified a SNP classifier and clinical indicators that can predict the prognosis of glioma patients and established a prognostic prediction model in the Chinese Han population. This study offers valuable insights for clinical practice, enabling improved evaluation of patients' prognosis and informing treatment options.

Long-term Bisphenol S exposure induced gut microbiota dysbiosis, obesity, hepatic lipid accumulation, intestinal lesions and dyslipidemia in mice.

Bisphenol S (BPS) is a commonly detected chemical raw material in water, which poses significant threats to both the ecological environment and human health. Despite being recognized as a typical endocrine disruptor and a substitute for Bisphenol A, the toxicological effects of BPS remain nonnegligible. In order to comprehensively understand the health impacts of BPS, a long-term (154 days) exposure experiment was conducted on mice, during which the physiological indicators of the liver, intestine, and blood were observed. The findings revealed that exposure to BPS resulted in dysbiosis of the gut microbiota, obesity, hepatic lipid accumulation, intestinal lesions, and dyslipidemia. Furthermore, there exists a significant correlation between gut microbiota and indicators of host health. Consequently, the identification of specific gut microbiota can be considered as potential biomarkers for the evaluation of risk associated with BPS. This study will effectively address the deficiency in toxicological data pertaining to BPS. The novel BPS data obtained from this research can serve as a valuable reference for professionals in the field.

[Analysis of constituents in different parts of Forsythia suspensa by UPLC-Q-TOF-MS and evaluation of their anti-inflammatory activity].

This study aims to characterize and identify the chemical constituents in 11 parts of Forsythia suspensa by using ultra-performance liquid chromatography-quadrupole time of flight-mass spectrometry(UPLC-Q-TOF-MS) combined with a self-established chemical constituent database, including leaves, flowers, fruits, green F. suspensa, old F. suspensa, and seeds. The quality attributes and differences of different parts of F. suspensa were evaluated by principal component analysis, partial least square discriminant analysis, and other stoichiometric methods. A total of 79 compounds were identified, including 13 phenylethanol glycosides, 10 lignans, 12 flavonoids, 10 organic acids, 14 terpenoids, and 20 other types of compounds. Among them, 34 compounds were the main variables of difference between the different parts of F. suspensa, and the content of each component was relatively higher in the leaves and green F. suspensa. The LPS-induced inflammation model of RAW264.7 cells was applied to study the anti-inflammatory activity of the extracts of the different parts of F. suspensa and the main constituents. The results show that the extracts of green F. suspensa, flower, twig, and stem exhibited anti-inflammatory activity, and the constituents such as forsythoside A, phyllyrin, phillygenin, and(+)-pinoresinol-ß-D-glucopyranoside could significantly inhibit anti-inflammatory activity released by NO. The chemical constituent in different parts of F. suspensa is analyzed comprehensively, and the anti-inflammatory activity is evaluated in this study, which provides a reference for the development and comprehensive utilization of F. suspensa resources.

[Status of outcome measures in randomized controlled trials of kidney-tonifying and blood-activating method in treatment of knee osteoarthritis].

This study assesses the status of outcome measures in the randomized controlled trial(RCT) involving the kidney-tonif-ying and blood-activating method for treating knee osteoarthritis(KOA), aiming to establish a theoretical foundation for the development of a core set of outcome measures in traditional Chinese medicine(TCM) treatment of KOA. The relevant articles were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, in addition to ClinicalTrials.gov and the China Clinical Trial Registration Center, with the time interval from inception to August 2023. The RCT of treating KOA with the kidney-tonifying and blood-activating method was included. Two assessors independently conducted literature screening, data collection, and qualitative analysis to compile the outcome measure results. A total of 350 RCTs were included, involving 165 outcome measures with the total frequency of 1 462. These outcome measures were categorized into six domains: symptom and sign measures(23) with the frequency of 718(49.1%), TCM symptom and syndrome measures(3) with the frequency of 53(3.6%), physical examination measures(130) with the frequency of 506(34.6%), quality of life measures(4) with the frequency of 20(1.3%), long-term efficacy measures(2) with the frequency of 6(0.4%), and safety measures(3) with the frequency of 159(10.9%). Additionally, 53 studies used TCM syndrome and symptom scores as indicators of efficacy, employing eight distinct measurement tools. The RCTs involving the kidney-tonifying and blood-activating method for treating KOA had a variety of problems, such as unclear prio-ritization of outcome measures, diversity in measurement tools, absence of standardized assessment criteria for specific measures, and non-standardized usage. These problems affected the research quality and reliability. Hence, it is advisable to draw upon international expertise, improve research design, and merge TCM efficacy characteristics with clinical research to establish a core set of KOA outcome measures aligned with TCM principles.

Tailoring Charge Flow in Carbon-Defective Cu-MOF with Pd Nanoparticles: A Boost for Visible Light Organic Photoelectrochemical Transistor in Bioanalysis.

The photoactive material was of significant importance in organic photoelectrochemical transistor (OPECT) bioanalysis as it influences the photoinduced voltage and the µC* product, resulting in a varying sensor sensitivity. The utilization of metal-organic frameworks (MOFs) as photoactive materials in OPECT analysis is promising, yet it remains a grand challenge due to the inherently narrow light absorption range and high electron-hole recombination rate. Herein, Pd NPs were encapsulated as electron acceptors into the Cu-MOF using a double-solvent method, followed by pyrolysis at the proper temperature. After pyrolysis, Cu-MOF transformed into a carbon defect-rich composite of CuO and Cu2O while retaining its high porosity and structural morphology. The resulting carbon defect-rich pyrolysis Cu-MOF (p-Cu-MOF) served as an active support, facilitating the separation of electrons and holes. The photoelectrons trigger the electron transfer of adjacent active metal components and the formation of a Schottky junction between Pd and the MOFs. This effect induces the electron donation from the MOFs. Moreover, Pd/pyrolysis Cu-MOF exhibits significantly higher visible light absorption, better water stability, and higher electrical conductivity compared to Cu-MOF and Pd/Cu-MOF. An OPECT sensor was fabricated by utilizing Pd/p-Cu-MOF as the photoactive material and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as the channel material on an integrated laser-etched FTO. The aptamer was used as the recognition element, enabling sensitive and efficient detection of residual isocarbophos.

Association between hyperuricemia and ultrasound-detected hand synovitis.

OBJECTIVE: Although hand synovitis is prevalent in the older population, the aetiology remains unclear. Hyperuricemia, a modifiable metabolic disorder, may serve as an underlying mechanism of hand synovitis, but little is known about their relationship. We assessed the association between hyperuricemia and hand synovitis in a large population-based sample. METHODS: We performed a cross-sectional study in Longshan County, Hunan Province, China. Hyperuricemia was defined as a serum urate >420 µmol/L in men and >360 µmol/L in women. Ultrasound examinations were performed on both hands of 4,080 participants, and both grey-scale synovitis and Power Doppler signal (PDS) were assessed using semiquantitative scores (grades 0-3). We evaluated the association of hyperuricemia with hand grey-scale synovitis (grade ≥2) and PDS (grade ≥1), respectively, adjusting for age, sex and body mass index. RESULTS: All required assessments for analysis were available on 3,286 participants. The prevalence of hand grey-scale synovitis was higher among participants with hyperuricemia (30.0%) than those with normouricemia (23.3%), with an adjusted odds ratio (aOR) of 1.28 (95% confidence interval [CI]:1.00-1.62). Participants with hyperuricemia also had higher prevalence of PDS (aOR=2.36, 95% CI:1.15-4.81). Furthermore, hyperuricemia positively associated, both at the hand and joint levels, with presence of grey-scale synovitis (aOR=1.27, 95% CI:1.00-1.60, and adjusted prevalence ratio [aPR]=1.26, 95% CI:1.10-1.44, respectively), and PDS (aOR=2.35, 95% CI:1.15-4.79, and aPR=2.34, 95% CI:1.28-4.30, respectively). CONCLUSION: This population-based study provides more evidences for a positive association between hyperuricemia and prevalent hand synovitis.

Antibiofilm activity of polyethylene glycol-quercetin nanoparticles-loaded gelatin-N,O-carboxymethyl chitosan composite nanogels against Staphylococcus epidermidis.

BACKGROUND: Biofilms, such as those from Staphylococcus epidermidis, are generally insensitive to traditional antimicrobial agents, making it difficult to inhibit their formation. Although quercetin has excellent antibiofilm effects, its clinical applications are limited by the lack of sustained and targeted release at the site of S. epidermidis infection. OBJECTIVES: Polyethylene glycol-quercetin nanoparticles (PQ-NPs)-loaded gelatin-N,O-carboxymethyl chitosan (N,O-CMCS) composite nanogels were prepared and assessed for the on-demand release potential for reducing S. epidermidis biofilm formation. METHODS: The formation mechanism, physicochemical characterization, and antibiofilm activity of PQ-nanogels against S. epidermidis were studied. RESULTS: Physicochemical characterization confirmed that PQ-nanogels had been prepared by the electrostatic interactions between gelatin and N,O-CMCS with sodium tripolyphosphate. The PQ-nanogels exhibited obvious pH and gelatinase-responsive to achieve on-demand release in the micro-environment (pH 5.5 and gelatinase) of S. epidermidis. In addition, PQ-nanogels had excellent antibiofilm activity, and the potential antibiofilm mechanism may enhance its antibiofilm activity by reducing its relative biofilm formation, surface hydrophobicity, exopolysaccharides production, and eDNA production. CONCLUSIONS: This study will guide the development of the dual responsiveness (pH and gelatinase) of nanogels to achieve on-demand release for reducing S. epidermidis biofilm formation.

Associations between hyperuricemia and ultrasound-detected knee synovial abnormalities in middle-aged and older population: a cross-sectional study.

OBJECTIVES: Knee synovial abnormalities, potentially treatment targets for knee pain and osteoarthritis, are common in middle-aged and older population, but its etiology remains unclear. We examined the associations between hyperuricemia and knee synovial abnormalities detected by ultrasound in a general population sample. METHODS: Participants aged ≥ 50 years were from a community-based observational study. Hyperuricemia was defined as serum urate (SU) level > 416 µmol/L in men and > 357 µmol/L in women. Ultrasound of both knees was performed to determine the presence of synovial abnormalities, i.e., synovial hypertrophy, effusion, or Power Doppler signal (PDS). We examined the relation of hyperuricemia to prevalence of knee synovial abnormalities and its laterality, and the dose-response relationships between SU levels and the prevalence of knee synovial abnormalities. RESULTS: In total, 3,405 participants were included in the analysis. Hyperuricemia was associated with higher prevalence of knee synovial abnormality (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI]: 1.02 to 1.43), synovial hypertrophy (aOR = 1.33, 95% CI: 1.05 to 1.68), and effusion (aOR = 1.21, 95% CI: 1.02 to 1.44), respectively. There were dose-response relationships between SU levels and synovial abnormalities. Additionally, the hyperuricemia was more associated with prevalence of bilateral than with that of unilateral knee synovial abnormality, synovial hypertrophy, or effusion; however, no significant association was observed between hyperuricemia and PDS. CONCLUSION: In this population-based study we found that hyperuricemia was associated with higher prevalence of knee synovial abnormality, synovial hypertrophy and effusion, suggesting that hyperuricemia may play a role in pathogenesis of knee synovial abnormalities.

Gustatory dysfunction and long COVID in Chinese patients with COVID-19: A 6-month follow-up study.

AIMS: To evaluate long COVID of gustatory dysfunction and the associated risk factors regarding onset and recovery in Chinese patients. METHODS: We conducted a cross-sectional study of patients with SARS-CoV-2 Omicron infection at Changxing Mobile Cabin Hospital in Shanghai, China, from March to May 2022. A prospective follow-up of patients with gustatory dysfunction was conducted at 6 months after discharge. RESULTS: In total, 18.48% (241/1304) reported gustatory dysfunction. The 6-month follow-up response rate was 89.63% (216/241) and 74.02% recovered their taste sense within 1-3 weeks. A total of 20.37% of patients (44/216) presented with long COVID. Symptoms persisted for 12 patients (5.56%) after 6 months. Having multiple taste impairments (OR, 2.364; 95% CI, 1.286-4.348; p = 0.006) was associated with a higher risk of gustatory dysfunction with long COVID. Having received a COVID-19 vaccine booster was positively associated with taste sensation recovery (HR, 1.344; 95% CI, 1.012-1.785; p = 0.041). CONCLUSIONS: About 20.37% of patients with COVID-19 might develop long COVID of gustatory dysfunction and 5.56% with persisting changes in their sense of taste. Most patients recovered taste sensations within 1-3 weeks after COVID-19 symptom onset and receiving a booster shot of the COVID-19 vaccine presented a protective effect on the taste sensation recovery.

SGLT2 inhibition, high-density lipoprotein, and kidney function: a mendelian randomization study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibition is recognized for its evident renoprotective benefits in diabetic renal disease. Recent data suggest that SGLT2 inhibition also slows down kidney disease progression and reduces the risk of acute kidney injury, regardless of whether the patient has diabetes or not, but the mechanism behind these observed effects remains elusive. The objective of this study is to utilize a mendelian randomization (MR) methodology to comprehensively examine the influence of metabolites in circulation regarding the impact of SGLT2 inhibition on kidney function. METHODS: We used a MR study to obtain associations between genetic proxies for SGLT2 inhibition and kidney function. We retrieved the most recent and comprehensive summary statistics from genome-wide association studies (GWAS) that have been previously published and involved kidney function parameters such as estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and albuminuria. Additionally, we included blood metabolite data from 249 biomarkers in the UK Biobank for a more comprehensive analysis. We performed MR analyses to explore the causal relationships between SGLT2 inhibition and kidney function and two-step MR to discover potential mediating metabolites. RESULTS: The study found that a decrease in HbA1c levels by one standard deviation, which is genetically expected to result in SGLT2 inhibition, was linked to a decreased likelihood of developing type 2 diabetes mellitus (T2DM) (odds ratio [OR] = 0.55 [95% CI 0.35, 0.85], P = 0.007). Meanwhile, SGLT2 inhibition also protects eGFR (ß = 0.05 [95% CI 0.03, 0.08], P = 2.45 × 10- 5) and decreased UACR (-0.18 [95% CI -0.33, -0.02], P = 0.025) and albuminuria (-1.07 [95% CI -1.58, -0.57], P = 3.60 × 10- 5). Furthermore, the study found that of the 249 metabolites present in the blood, only one metabolite, specifically the concentration of small high-density lipoprotein (HDL) particles, was significantly correlated with both SGLT2 inhibition and kidney function. This metabolite was found to play a crucial role in mediating the improvement of renal function through the use of SGLT2 inhibition (ß = 0.01 [95% CI 0.005, 0.018], P = 0.001), with a mediated proportion of 13.33% (95% CI [5.71%, 26.67%], P = 0.020). CONCLUSIONS: The findings of this investigation provide evidence in favor of a genetically anticipated biological linkage between the inhibition of SGLT2, the presence of circulating metabolites, and renal function. The findings demonstrate that the protective effect of SGLT2 inhibition on renal function is mostly mediated by HDL particle concentrations in circulating metabolites. These results offer significant theoretical support for both the preservation of renal function and a better comprehension of the mechanisms underlying SGLT2 inhibition.

Bactericidal efficacy of plasma-activated water against Vibrio parahaemolyticus on Litopenaeus vannamei.

In this study, the antimicrobial mechanism of plasma-activated water (PAW) against Vibrio parahaemolyticus and the effectiveness of PAW in artificially contaminated Litopenaeus vannamei were investigated. The results demonstrated a significant reduction (p < 0.05) in viable counts of V. parahaemolyticus with increasing plasma discharge time (5, 10, 20, and 30 min) and PAW immersion time (3, 5, 10, 20, and 30 s). Specifically, the count of V. parahaemolyticus decreased by 2.1, 2.7, 3.3, and 4.4 log CFU/mL after exposed to PAW 5, PAW 10, PAW 20, and PAW 30 for 30 s, respectively. Significant cell surface wrinkling, accompanied by notable nucleic acid and protein leakage were observed after treatment with PAW. The permeability of the inner and outer cell membranes was significantly increased (p < 0.05), along with an increase in electrical conductivity (p < 0.05). The reactive oxygen species (ROS) within V. parahaemolyticus cells were significantly increased (p < 0.05), while superoxide dismutase (SOD) activity, and the relative expression of the ompW, emrD, and luxS genes were significantly decreased (p < 0.05). A reduction number of 1.3, 1.8, 2.1, and 2.2 log CFU/g of V. parahaemolyticus in artificially contaminated L. vannamei was obtained with PAW for 5 min. The study elucidated that PAW could destroy cell membranes, leading to cell death. The findings would strengthen strategies for V. parahaemolyticus control and provide a potential application of PAW for preserving aquatic products.

Construction and validation of a machine learning model for the diagnosis of juvenile idiopathic arthritis based on fecal microbiota.

Purpose: Human gut microbiota has been shown to be significantly associated with various inflammatory diseases. Therefore, this study aimed to develop an excellent auxiliary tool for the diagnosis of juvenile idiopathic arthritis (JIA) based on fecal microbial biomarkers. Method: The fecal metagenomic sequencing data associated with JIA were extracted from NCBI, and the sequencing data were transformed into the relative abundance of microorganisms by professional data cleaning (KneadData, Trimmomatic and Bowtie2) and comparison software (Kraken2 and Bracken). After that, the fecal microbes with high abundance were extracted for subsequent analysis. The extracted fecal microbes were further screened by least absolute shrinkage and selection operator (LASSO) regression, and the selected fecal microbe biomarkers were used for model training. In this study, we constructed six different machine learning (ML) models, and then selected the best model for constructing a JIA diagnostic tool by comparing the performance of the models based on a combined consideration of area under receiver operating characteristic curve (AUC), accuracy, specificity, F1 score, calibration curves and clinical decision curves. In addition, to further explain the model, Permutation Importance analysis and Shapley Additive Explanations (SHAP) were performed to understand the contribution of each biomarker in the prediction process. Result: A total of 231 individuals were included in this study, including 203 JIA patients and Non-JIA individuals. In the analysis of diversity at the genus level, the alpha diversity represented by Shannon value was not significantly different between the two groups, while the belt diversity was slightly different. After selection by LASSO regression, 10 fecal microbe biomarkers were selected for model training. By comparing six different models, the XGB model showed the best performance, which average AUC, accuracy and F1 score were 0.976, 0.914 and 0.952, respectively, thus being used to construct the final JIA diagnosis model. Conclusion: A JIA diagnosis model based on XGB algorithm was constructed with excellent performance, which may assist physicians in early detection of JIA patients and improve the prognosis of JIA patients.

Isothermal Reciprocal Catalytic DNA Circuit for Sensitive Analysis of Kanamycin.

Inappropriate use of veterinary drugs can result in the presence of antibiotic residues in animal-derived foods, which is a threat to human health. A simple yet efficient antibiotic-sensing method is highly desirable. Programmable DNA amplification circuits have supplemented robust toolkits for food contaminants monitoring. However, they currently face limitations in terms of their intricate design and low signal gain. Herein, we have engineered a robust reciprocal catalytic DNA (RCD) circuit for highly efficient bioanalysis. The trigger initiates the cascade hybridization reaction (CHR) to yield plenty of repeated initiators for activating the rolling circle amplification (RCA) circuit. Then the RCA-generated numerous reconstituted triggers can reversely stimulate the CHR circuit. This results in a self-sufficient supply of numerous initiators and triggers for the successive cross-invasion of CHR and RCA amplifiers, thus leading to exponential signal amplification for the highly efficient detection of analytes. With its flexible programmability and modular features, the RCD amplifier can serve as a universal toolbox for the high-performance and accurate sensing of kanamycin in buffer and food samples including milk, honey, and fish, highlighting its enormous promise for low-abundance contaminant analysis in foodstuffs.

SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl- concentration.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disrupts the epithelial barrier and triggers airway inflammation. The envelope (E) protein, a core virulence structural component of coronaviruses, may play a role in this process. Pathogens could interfere with transepithelial Cl- transport via impairment of the cystic fibrosis transmembrane conductance regulator (CFTR), which modulates nuclear factor κB (NF-κB) signaling. However, the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function, Cl- transport and the robust inflammatory response remain to be elucidated. Here, we have demonstrated that E protein down-regulated the expression of tight junctional proteins, leading to the disruption of the airway epithelial barrier. In addition, E protein triggered the activation of Toll-like receptor (TLR) 2/4 and downstream c-Jun N-terminal kinase (JNK) signaling, resulting in an increased intracellular Cl- concentration ([Cl-]i) via up-regulating phosphodiesterase 4D (PDE4D) expression in airway epithelial cells. This elevated [Cl-]i contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1 (SGK1). Moreover, blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E protein. Overall, these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

Radiomics-based nomogram guides adaptive de-intensification in locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy.

OBJECTIVES: This study aimed to construct a radiomics-based model for prognosis and benefit prediction of concurrent chemoradiotherapy (CCRT) versus intensity-modulated radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (LANPC) following induction chemotherapy (IC). MATERIALS AND METHODS: A cohort of 718 LANPC patients treated with IC + IMRT or IC + CCRT were retrospectively enrolled and assigned to a training set (n = 503) and a validation set (n = 215). Radiomic features were extracted from pre-IC and post-IC MRI. After feature selection, a delta-radiomics signature was built with LASSO-Cox regression. A nomogram incorporating independent clinical indicators and the delta-radiomics signature was then developed and evaluated for calibration and discrimination. Risk stratification by the nomogram was evaluated with Kaplan-Meier methods. RESULTS: The delta-radiomics signature, which comprised 19 selected features, was independently associated with prognosis. The nomogram, composed of the delta-radiomics signature, age, T category, N category, treatment, and pre-treatment EBV DNA, showed great calibration and discrimination with an area under the receiver operator characteristic curve of 0.80 (95% CI 0.75-0.85) and 0.75 (95% CI 0.64-0.85) in the training and validation sets. Risk stratification by the nomogram, excluding the treatment factor, resulted in two groups with distinct overall survival. Significantly better outcomes were observed in the high-risk patients with IC + CCRT compared to those with IC + IMRT, while comparable outcomes between IC + IMRT and IC + CCRT were shown for low-risk patients. CONCLUSION: The radiomics-based nomogram can predict prognosis and survival benefits from concurrent chemotherapy for LANPC following IC. Low-risk patients determined by the nomogram may be potential candidates for omitting concurrent chemotherapy during IMRT. CLINICAL RELEVANCE STATEMENT: The radiomics-based nomogram was constructed for risk stratification and patient selection. It can help guide clinical decision-making for patients with locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy, and avoid unnecessary toxicity caused by overtreatment. KEY POINTS: • The benefits from concurrent chemotherapy remained controversial for locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy. • Radiomics-based nomogram achieved prognosis and benefits prediction of concurrent chemotherapy. • Low-risk patients defined by the nomogram were candidates for de-intensification.

Very important pharmacogenetic variants landscape and potential clinical relevance in the Zhuang population from Yunnan province.

The gradual evolution of pharmacogenomics has shed light on the genetic basis for inter-individual drug response variations across diverse populations. This study aimed to identify pharmacogenomic variants that differ in Zhuang population compared with other populations and investigate their potential clinical relevance in gene-drug and genotypic-phenotypic associations. A total of 48 variants from 24 genes were genotyped in 200 Zhuang subjects using the Agena MassARRAY platform. The allele frequencies and genotype distribution data of 26 populations were obtained from the 1000 Genomes Project, followed by a comparison and statistical analysis. After Bonferroni correction, significant differences in genotype frequencies were observed of CYP3A5 (rs776746), ACE (rs4291), KCNH2 (rs1805123), and CYP2D6 (rs1065852) between the Zhuang population and the other 26 populations. It was also found that the Chinese Dai in Xishuangbanna, China, Han Chinese in Beijing, China, and Southern Han Chinese, China showed least deviation from the Zhuang population. The Esan in Nigeria, Gambian in Western Division, The Gambia, and Yoruba in Ibadan, Nigeria exhibited the largest differences. This was also proved by structural analysis, Fst analysis and phylogenetic tree. Furthermore, these differential variants may be associated with the pharmacological efficacy and toxicity of Captopril, Amlodipine, Lisinopril, metoclopramide, and alpha-hydroxymetoprolol in the Zhuang population. Our study has filled the gap of pharmacogenomic information in the Zhuang population and has provided a theoretical framework for the secure administration of drugs in the Zhuang population.