Impact of prostate MRI image quality on diagnostic performance for clinically significant prostate cancer (csPCa).

OBJECTIVES: With the widespread clinical application of prostate magnetic resonance imaging (MRI), there has been an increasing demand for lesion detection and accurate diagnosis in prostate MR, which relies heavily on satisfactory image quality. Focusing on the primary sequences involved in Prostate Imaging Reporting and Data System (PI-RADS), this study have evaluated common quality issues in clinical practice (such as signal-to-noise ratio (SNR), artifacts, boundaries, and enhancement). The aim of the study was to determine the impact of image quality on clinically significant prostate cancer (csPCa) detection, positive predictive value (PPV) and radiologist's diagnosis in different sequences and prostate zones. METHODS: This retrospective study included 306 patients who underwent prostate MRI with definitive pathological reports from February 2021 to December 2022. All histopathological specimens were evaluated according to the recommendations of the International Society of Urological Pathology (ISUP). An ISUP Grade Group ≥ 2 was considered as csPCa. Three radiologists from different centers respectively performed a binary classification assessment of image quality in the following ten aspects: (1) T2WI in the axial plane: SNR, prostate boundary conditions, the presence of artifacts; (2) T2WI in the sagittal or coronal plane: prostate boundary conditions; (3) DWI: SNR, delineation between the peripheral and transition zone, the presence of artifacts, the matching of DWI and T2WI images; (4) DCE: the evaluation of obturator artery enhancement, the evaluation of dynamic contrast enhancement. Fleiss' Kappa was used to determine the inter-reader agreement. Wilson's 95% confidence interval (95% CI) was used to calculate PPV. Chi-square test was used to calculate statistical significance. A p-value < 0.05 was considered statistically significant. RESULTS: High-quality images had a higher csPCa detection rate (56.5% to 64.3%) in axial T2WI, DWI, and DCE, with significant statistical differences in SNR in axial T2WI (p 0.002), the presence of artifacts in axial T2WI (p 0.044), the presence of artifacts in DWI (p < 0.001), and the matching of DWI and T2WI images (p < 0.001). High-quality images had a higher PPV (72.5% to 78.8%) and showed significant statistical significance in axial T2WI, DWI, and DCE. Additionally, we found that PI-RADS 3 (24.0% to 52.9%) contained more low-quality images compared to PI-RADS 4-5 (20.6% to 39.3%), with significant statistical differences in the prostate boundary conditions in axial T2WI (p 0.048) and the presence of artifacts in DWI (p 0.001). Regarding the relationship between csPCa detection and image quality in different prostate zones, this study found that significant statistical differences were only observed between high- (63.5% to 75.7%) and low-quality (30.0% to 50.0%) images in the peripheral zone (PZ). CONCLUSION: Prostate MRI quality may have an impact on the diagnostic performance. The poorer image quality is associated with lower csPCa detection rates and PPV, which can lead to an increase in radiologist's ambiguous diagnosis (PI-RADS 3), especially for the lesions located at PZ.

Cytotoxic Pentaketide-Sesquiterpenes from the Marine-Derived Fungus Talaromyces variabilis M22734.

Talaromyces, a filamentous fungus widely distributed across terrestrial and marine environments, can produce a diverse array of natural products, including alkaloids, polyketones, and polyketide-terpenoids. Among these, chrodrimanins represented a typical class of natural products. In this study, we isolated three previously undescribed pentaketide-sesquiterpenes, 8,9-epi-chrodrimanins (1-3), along with eight known compounds (4-11). The structures of compounds 1-3 were elucidated using nuclear magnetic resonance (NMR) and mass spectrometry (MS), while their absolute configurations were determined through X-ray crystallography and electronic circular dichroism (ECD) computations. The biosynthetic pathways of compounds 1-3 initiate with 6-hydroxymellein and involve multiple stages of isoprenylation, cyclization, oxidation, and acetylation. We selected four strains of gastrointestinal cancer cells for activity evaluation. We found that compound 3 selectively inhibited MKN-45, whereas compounds 1 and 2 exhibited no significant inhibitory activity against the four cell lines. These findings suggested that 8,9-epi-chrodrimanins could serve as scaffold compounds for further structural modifications, potentially leading to the development of targeted therapies for gastric cancer.

Introducing Bacillus natto and Propionibacterium shermanii into soymilk fermentation: A promising strategy for quality improvement and bioactive peptide production during in vitro digestion.

Herein, the texture properties, polyphenol contents, and in vitro protein digestion characteristics of soymilk single- or co-fermented by non-typical milk fermenter Bacillus natto (B. natto), Propionibacterium freudenreichii subsp. shermanii (P. shermanii), and traditional milk fermenter were evaluated. Co-fermenting procedure containing B. natto or P. shermanii could raise the amounts of gallic acid, caffeic acid, and GABA when compared to the unfermented soymilk. Co-fermented soymilk has higher in vitro protein digestibility and nutritional protein quality. Through peptidomic analysis, the co-work of P. shermanii and Lactobacillus plantarum (L. plantarum) may release the highest relative percentage of bioactive peptides, while the intervention of B. natto and Streptococcus thermophilus (S. thermophilus) resulted in more differentiated peptides. The multi-functional bioactive peptides were mainly released from glycine-rich protein, ß-conglycinin alpha subunit 1, and ACB domain-containing protein. These findings indicated the potential usage of B. natto/S. thermophilus or P. shermanii/L. plantarum in bio-enhanced soymilk fermentation.

The role of TrkB signaling-mediated synaptic plasticity in the antidepressant properties of catalpol, the main active compound of Rehmannia glutinosa Libosch.

ETHNOPHARMACOLOGICAL RELEVANCE: Rehmannia glutinosa Libosch. (RGL) is a famous ethnic medicine contained in antidepressant Chinese medicine formulas and is traditionally clinically used for depression. We have recently confirmed that RGL enhanced synaptic plasticity in a mouse model of Chinese medical syndrome and that catalpol may be the representatively pharmacological component responsible for its improvement in synaptic plasticity and treatment of depression. Impaired synaptic plasticity is closely linked to major depression. Tyrosine kinase receptor B (TrkB) signaling has recently been discovered as a key pathway for synaptic plasticity improvement and antidepressant discovery. However, to date, it is unknown whether the target of catalpol to improve synaptic plasticity involves TrkB and whether its antidepressant mechanism involves synaptic plasticity mediated by TrkB signaling. AIM OF STUDY: This study aims to elucidate the potential antidepressant target and mechanisms of catalpol, the main active compound of RGL, through TrkB signaling-mediated synaptic plasticity. MATERIALS AND METHODS: We have recently predicted through molecular networking strategy (including network pharmacology, molecular docking, and molecular dynamics simulation) that catalpol may exert its antidepressant effects by regulating TrkB signaling and thus modulating essential synaptic plasticity proteins. Then, this study used classic behavioral tests, targeted diagnostic reagents, Nissl and Golgi staining, immunohistochemical analysis, immunofluorescence analysis, Western blot, enzyme-linked immunosorbent assay, and Real-time PCR to confirm the potential target and signaling of catalpol to improve synaptic plasticity for the treatment of depression. RESULTS: The data showed that catalpol could improve synaptic plasticity and depressive behaviors, and its action pathway was predicted to involve TrkB signaling. Subsequently, the blockade of TrkB abolished the improvement of synaptic plasticity by catalpol and its antidepressant properties, which validated that TrkB signaling was the key pathway for catalpol to improve synaptic plasticity and exert antidepressant properties. Inhibition of COX-2 was likely to be a necessary facilitator for the antidepressant efficacy of catalpol via the TrkB target and TrkB-mediated synaptic plasticity. CONCLUSION: TrkB signaling-mediated synaptic plasticity plays a key role in the antidepressant properties of catalpol. This study provides critical information for the development of new and targeted antidepressant therapies or treatment strategies by catalpol. However, considering the existence of sex differences in depression (female depression is 2-3 times than that of males) and not exploring the antidepressant sex specificity of catalpol is a limitation, we will investigate the sex specificity of the antidepressant effects and molecular mechanisms of catalpol on sex-specific animals in the future to provide a preclinical basis for more accurate and targeted medication of catalpol.

Sustainable H2O2 production in a floating dual-cathode electro-Fenton system for efficient decontamination of organic pollutants.

Electrochemical advanced oxidation processes (EAOPs) based on natural air diffusion electrode (NADE) promise efficient and affordable advanced oxidation water purification, but the sustainable operation of such reaction systems remains challenging due to severe cathode electrowetting. Herein, a novel floating cathode (FC) composed of a stable hydrophobic three-phase interface was established by designing a flexible catalytic layer of FC. This innovative electrode configuration could effectively prolong the service life of the cathode by mitigating the interference of H2 bubbles from the hydrogen evolution reaction (HER), and the H2O2 production rate reached 37.59 mg h-1·cm-2 and realize a long-term stable operation for 10 h. Additionally, an FC/carbon felt (CF) dual-cathode electro-Fenton system was constructed for in situ sulfamethoxazole (SMX) degradation. Efficient H2O2 production on FC and Fe(III) reduction on CF were synchronously achieved, attaining excellent degradation efficiency for both SMX (ca. 100%) with 2.5 mg L-1 of Fe(Ⅱ) injection. For real wastewater, the COD removal of the FC/CF dual-cathode electro-Fenton system was stabilized at exceeding 75%. The practical application potential of the FC/CF dual-cathode electro-Fenton system was also demonstrated for the treatment of actual landfill leachate in continuous flow mode. This work provides a valuable path for constructing a sustainable dual-cathode electro-Fenton system for actual wastewater treatment.

Association Between Serum Zinc and Non-Alcoholic Fatty Liver Disease and Advanced Liver Fibrosis: NHANES 2011-2016.

Limited and inconclusive evidence exists regarding the correlation between serum zinc levels and non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis. The objective of this cross-sectional study was to investigate the association between serum zinc concentration and both NAFLD and advanced liver fibrosis among the United States (US) adults. 3398 subjects from National Health and Nutrition Examination Survey (NHANES) 2011-2016 were included. Serum zinc concentration was measured by inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS). NAFLD was diagnosed with Hepatic Steatosis Index (HSI), and advanced fibrosis risk was assessed by NAFLD Fibrosis Score (NFS). Weighted logistic regression and restricted cubic splines (RCS) were used to examine the association between serum zinc concentration and NAFLD and advanced fibrosis. Linear trend tests were conducted by incorporating the median of serum zinc quartiles as a continuous variable in the models. We employed sensitivity analysis and subgroup analysis to enhance the robustness of our results. The results from the RCS regression revealed no evident nonlinear relationship between serum zinc concentration and the presence of NAFLD and advanced fibrosis (p-nonlinear > 0.05). Compared with those in the lowest quartile (Q1) of serum zinc concentrations, the odds ratios (95% confidence intervals) of NAFLD were 1.49 (0.89,2.49) in Q2, 0.99 (0.68,1.45) in Q3, and 2.00 (1.40,2.86) in Q4 (p-trend = 0.002). Similarly, the odds ratios (95% confidence intervals) for advanced fibrosis in Q2-4 compared to Q1 were 0.86 (0.50,1.47), 0.60 (0.26,1.39), and 0.41 (0.21,0.77), respectively (p-trend = 0.006). Subgroup analyses and sensitivity analyses reinforce the same conclusion. The investigation revealed a positive linear relationship between serum zinc concentrations and the probability of developing NAFLD. Conversely, an inverse correlation was observed between serum zinc concentrations and the incidence of advanced liver fibrosis among individuals diagnosed with NAFLD.

Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.

Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.

Clinical Characteristics and 2-Year Outcomes of Chronic Obstructive Pulmonary Disease Patients With High Blood Eosinophil Counts: A Population-based Prospective Cohort Study in China.

BACKGROUND: High blood eosinophil count (BEC) is a useful biomarker for guiding inhaled corticosteroid therapy in patients with chronic obstructive pulmonary disease (COPD), yet its implications in a community setting remain underexplored. This study aimed to elucidate the clinical characteristics and outcomes of COPD patients with high BEC within the Chinese community. METHODS: We obtained baseline and 2-year follow-up data from COPD patients (post-bronchodilator forced expiratory volume in 1 second/forced vital capacity <0.70) in the early COPD study. Patients with a BEC ≥300cells/µL were classified as the high BEC group. We assessed differences in the clinical characteristics and outcomes between high and low BEC patients. Subgroup analyses were conducted on COPD patients without a history of corticosteroid use or asthma. RESULTS: Of the 897 COPD patients, 205 (22.9%) had high BEC. At baseline, high BEC patients exhibited a higher proportion of chronic respiratory symptoms, lower lung function, and more severe small airway dysfunction than low BEC patients. Over the 2-year period, high BEC patients experienced a significantly higher risk of acute exacerbations (relative risk: 1.28, 95% confidence interval: 1.09-1.49; P=0.002), even after adjusting for confounders. No significant difference was observed in lung function decline rates. The subgroup analysis yielded consistent results. CONCLUSIONS: COPD patients with high BEC in a Chinese community exhibited poorer health status, more severe small airway dysfunction, and a higher risk of exacerbations. Future research should explore the pathological mechanisms underlying the poorer prognosis in patients with high BEC.

Clinical features and 1-year outcomes of variable obstruction in participants with preserved spirometry: results from the ECOPD study in China.

BACKGROUND: There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes. METHODS: Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC <0.70) were compared with those without variable obstruction (prebronchodilator FEV1/FVC ≥0.70). We performed subgroup analyses in never smokers, former and current smokers, and different variable obstruction types (postbronchodilator FVC

p-n heterogeneous Sb2S3/SnO2 quantum dot anchored reduced graphene oxide nanosheets for high-performance lithium-ion batteries.

Antimony sulfide (Sb2S3) has a high theoretical specific capacity due to its two reaction mechanisms of conversion and alloying during the Li+-(de)intercalation process, thus becoming a promising lithium-ion battery (LIB) anode material. However, its poor inherent conductivity and large volume expansion during repeated Li+-(de)intercalation processes greatly hinder the in-depth development of Sb2S3 based LIB anode materials. Herein, an Sb2S3/SnO2@rGO composite was prepared by using an interface engineering technique involving metal-containing ionic liquid precursors, in which Sb2S3/SnO2 quantum dots (QDs) as p-n heterojunctions are uniformly anchored on the surface of reduced graphene oxide (rGO). The p-n heterogeneous interface between Sb2S3 and SnO2 QDs induces an internal electric field, promoting the electronic/ion transport during electrochemical reactions, and the QD-sized Sb2S3/SnO2 heterostructure with a larger surface area provides more active sites for Li+-(de)intercalation reactions. In addition, the rGO matrix acts as a buffer to prevent the aggregation of active Sb2S3 and SnO2 QDs, alleviate the volume expansion, and enhance the conductivity of the composite during repeated cycles. These advantages endow the designed Sb2S3/SnO2@rGO electrode with excellent reaction kinetics and good long cycling stability. As an anode material of LIBs, it can still provide a reversible specific capacity of 474 mA h g-1 after 2000 cycles at a high current density of 3.0 A g-1, which is superior to those of most of the previously reported Sb2S3-based carbon materials. The p-n heterostructure construction strategy of nano-metal sulfide/metal oxides in this work can provide inspiration for the design and synthesis of other advanced energy storage materials.

Optimized design of quaternary amino-functionalized chitosan fibers for ultra-high diclofenac adsorption from wastewater.

The extraction of non-steroidal anti-inflammatory drugs (NSAIDs) from water bodies is imperative due to the potential harm to humans and the ecosystem caused by NSAID-contaminated water. Quaternary amino-functionalized epichlorohydrin cross-linked chitosan fibers (QECFs), an economical and eco-friendly adsorbent, were successfully prepared using a simple and gentle method for efficient diclofenac (DCF) adsorption. Additionally, the optimized factors for the preparation of QECFs included epichlorohydrin concentration, pH, temperature, and (3-chloro-2-hydroxypropyl) trimethylammonium chloride (CHTAC) concentration. QECFs demonstrated excellent adsorption performance for DCF across a broad pH range of 7-12. The calculated maximum adsorption capacity and the amount of adsorbed DCF per adsorption site were determined to be 987.5 ± 20.1 mg/g and 1.2 ± 0.2, respectively, according to the D-R and Hill isotherm models, at pH 7 within 180 min. This performance surpassed that of previously reported adsorbents. The regeneration of QECFs could be achieved using a 0.5 mol/L NaOH solution within 90 min, with QECFs retaining their original fiber form and experiencing only a 9.18% reduction in adsorption capacity after 5 cycles. The Fourier transform infrared spectrometer and X-ray photoelectron spectroscopy were used to study the characterization of QECFs, the preparation mechanism of QECFs, and the adsorption mechanism of DCF by QECFs. Quaternary ammonium groups (R4N+) were well developed in QECFs through the reaction between amino/hydroxyl groups on chitosan and CHTAC, and approximately 0.98 CHTAC molecule with 0.98 R4N+ group were immobilized on each chitosan monomer. Additionally, these R4N+ on QECFs played a crucial role in the removal of DCF.

Gestational diabetes mellitus induces congenital anomalies of the kidney and urinary tract in mice by altering RET/MAPK/ERK pathway.

Gestational diabetes mellitus (GDM) presents a substantial population health concern. Previous studies have revealed that GDM can ultimately influence nephron endowment. In this study, we established a GDM mouse model to investigate the embryological alterations and molecular mechanisms underlying the development of congenital anomalies of the kidney and urinary tract (CAKUT) affected by GDM. Our study highlights that GDM could contribute to the manifestation of CAKUT, with prevalent phenotypes characterized by isolated hydronephrosis and duplex kidney complicated with hydronephrosis in mice. Ectopic ureteric buds (UBs) and extended length of common nephric ducts (CNDs) were noted in the metanephric development stage. The expression of Ret and downstream p-ERK activity were enhanced in UBs, which indicated the alteration of RET/MAPK/ERK pathway may be one of the mechanisms contributing to the increased occurrence of CAKUT associated with GDM.

GEN1 as a risk factor for human congenital anomalies of the kidney and urinary tract.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. METHODS: In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. RESULTS: Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. CONCLUSION: Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Harnessing Nanochaperone-Mediated Autophagy for Selective Clearance of Pathogenic Tau Protein in Alzheimer's Disease.

Accumulation of pathological tau is a hallmark of Alzheimer's disease (AD), which correlates more closely with cognitive impairment than does the amyloid-ß (Aß) burden. Autophagy is a powerful process for the clearance of toxic proteins including aberrant tau. However, compromised autophagy is demonstrated in neurodegeneration including AD, and current autophagy inducers remain enormously challenging due to inability of restoring autophagy pathway and lack of targeting specificity. Here, pathogenic tau-specific autophagy based on customized nanochaperone is developed for AD treatment. In this strategy, the nanochaperone can selectively bind to pathogenic tau and maintain tau homeostasis, thereby ensuring microtubule stability which is important for autophagy pathway. Meanwhile, the bound pathogenic tau can be sequestered in autophagosomes by in situ autophagy activation of nanochaperone. Consequently, autophagosomes wrapping with pathogenic tau are able to be trafficked along the stabilized microtubule to achieve successful fusion with lysosomes, resulting in the enhancement of autophagic flux and pathologic tau clearance. After treatment with this nanochaperone-mediated autophagy strategy, the tau burden, neuron damages, and cognitive deficits of AD mice are significantly alleviated in the brain. Therefore, this work represents a promising candidate for AD-targeted therapy and provides new insights into future design of anti-neurodegeneration drugs.

Controlling Interfacial Amidation Reaction Rate to Regulate Crystal Growth toward High-Performance FAPbBr3-Based Inverted Light-Emitting Diodes.

Controlling interfacial reactions is critical for zinc oxide (ZnO)-based inverted perovskite light-emitting diodes (PeLEDs), boosting the external quantum efficiency (EQE) of the near-infrared device to above 20%. However, violent interfacial reactions between the bromine-based perovskites and ZnO-based films severely limit the performance of inverted green PeLEDs, whose efficiency and stability lag far behind those of their near-infrared counterparts. Here, a controllable interfacial amidation between the bromine-based perovskites and magnesium-doped ZnO (ZnMgO) film utilizing caprylyl sulfobetaine (SFB) is realized. The SFB molecules strongly interact with formamidinium bromide, decelerating the amidation reaction between formamidinium and carboxylate groups on the ZnMgO film, thus regulating the crystallization of FAPbBr3. Combined with the passivation of benzylamine, a FAPbBr3 bulk film directly deposited on a ZnMgO substrate with single-crystal characteristics is obtained, exhibiting a high photoluminescence quantum yield of above 80%. The resultant PeLEDs demonstrate a peak EQE of exceeding 20% at a high luminance of 120,000 cd m-2 and a half lifetime of 26 min at 11,000 cd m-2, representing the state-of-the-art inverted green electroluminescence. This work resolves the crucial issues of violent interfacial reactions and provides a strategy toward inverted green PeLEDs with outstanding performance.

Clinical characterization and outcomes of impulse oscillometry-defined bronchodilator response: an ECOPD cohort-based study.

BACKGROUND: The clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR. METHODS: Participants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 0.70. IOS-BDR was defined as meeting any one of the following criteria: an absolute change in respiratory system resistance at 5 Hz ≤ - 0.137 kPa/L/s, an absolute change in respiratory system reactance at 5 Hz ≥ 0.055 kPa/L/s, or an absolute change in reactance area ≤ - 0.390 kPa/L. The association between IOS-BDR and a decline in lung function was explored with linear mixed-effects model. The association between IOS-BDR and the risk of acute respiratory exacerbations at the two-year follow-up was analyzed with the logistic regression model. RESULTS: This study involved 466 participants (92 participants with IOS-BDR and 374 participants without IOS-BDR). Participants with IOS-BDR had higher COPD assessment test and modified Medical Research Council dyspnea scale scores, more severe emphysema, air trapping, and rapid decline in FVC than those without IOS-BDR over 2-year follow-up. IOS-BDR was not associated with the risk of acute respiratory exacerbations at the 2-year follow-up. CONCLUSIONS: The participants with IOS-BDR had more respiratory symptoms, radiographic structural changes, and had an increase in decline in lung function than those without IOS-BDR. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.

The Rejuvenation and Functional Restoration of Aged Adipose Stem Cells by DUXAP10 Knockdown via the Regulation of the miR-214-3p/RASSF5 Axis.

Adipose stem cell (ASC)-based therapies provide an encouraging option for tissue repair and regeneration. However, the function of these cells declines with aging, which limits their clinical transformation. Recent studies have outlined the involvement of long non-coding RNAs in stem cell aging. Here, we reanalyzed our published RNA sequencing (RNA-seq) data profiling differences between ASCs from young and old donors and identified a lncRNA named double homeobox A pseudogene 10 (DUXAP10) as significantly accumulated in aged ASCs. Knocking down DUXAP10 promoted stem cell proliferation and migration and halted cell senescence and the secretion of proinflammatory cytokines. In addition, DUXAP10 was located in the cytoplasm and functioned as a decoy for miR-214-3p. miR-214-3p was downregulated in aged ASCs, and its overexpression rejuvenated aged ASCs and reversed the harm caused by DUXAP10. Furthermore, Ras Association Domain Family Member 5 (RASSF5) was the target of miR-214-3p and was upregulated in aged ASCs. Overexpressing DUXAP10 and inhibiting miR-214-3p both enhanced RASSF5 content in ASCs, while DUXAP10 knockdown promoted the therapeutic ability of aged ASCs for skin wound healing. Overall, this study offers new insights into the mechanism of age-related ASC dysfunction and names DUXAP10 and miR-214-3p as potential targets for energizing aged stem cells.

Transcriptome sequencing and expression analysis in peanut reveal the potential mechanism response to Ralstonia solanacearum infection.

BACKGROUND: Bacterial wilt caused by Ralstonia solanacearum severely affects peanut (Arachis hypogaea L.) yields. The breeding of resistant cultivars is an efficient means of controlling plant diseases. Therefore, identification of resistance genes effective against bacterial wilt is a matter of urgency. The lack of a reference genome for a resistant genotype severely hinders the process of identification of resistance genes in peanut. In addition, limited information is available on disease resistance-related pathways in peanut. RESULTS: Full-length transcriptome data were used to generate wilt-resistant and -susceptible transcript pools. In total, 253,869 transcripts were retained to form a reference transcriptome for RNA-sequencing data analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of differentially expressed genes revealed the plant-pathogen interaction pathway to be the main resistance-related pathway for peanut to prevent bacterial invasion and calcium plays an important role in this pathway. Glutathione metabolism was enriched in wilt-susceptible genotypes, which would promote glutathione synthesis in the early stages of pathogen invasion. Based on our previous quantitative trait locus (QTL) mapping results, the genes arahy.V6I7WA and arahy.MXY2PU, which encode nucleotide-binding site-leucine-rich repeat receptor proteins, were indicated to be associated with resistance to bacterial wilt. CONCLUSIONS: This study identified several pathways associated with resistance to bacterial wilt and identified candidate genes for bacterial wilt resistance in a major QTL region. These findings lay a foundation for investigation of the mechanism of resistance to bacterial wilt in peanut.

Streamlined synthesis of superstructure Ni-benzimidazole MOFs: Glucose electrochemical analysis.

The design and synthesis of efficient electrochemical sensors are crucial transformation technologies in electrochemistry. We successfully synthesize a three-dimensional Ni-metal-organic framework (MOF) nanostructured material with a superior architecture using benzimidazole and nickel nitrate as precursors at room temperature which is being applied in glucose electrochemical sensors. The reaction mechanism of M-6 during glucose detection is thoroughly studied using various characterization techniques, such as in situ Raman spectroscopy, in situ ultraviolet-visible spectrophotometry, synchrotron radiography, X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy. The research findings demonstrate that the M-6 material exhibits high sensitivity for glucose detection, with a sensitivity of 2199.88 mA M-1 cm-2. This study provides an important reference for designing more efficient electrochemical reaction systems and optimizing material performance. Furthermore, the superstructural design offers new ideas and possibilities for the development and application of similar materials.

vizAPA: visualizing dynamics of alternative polyadenylation from bulk and single-cell data.

MOTIVATION: Alternative polyadenylation (APA) is a widespread post-transcriptional regulatory mechanism across all eukaryotes. With the accumulation of genome-wide APA sites, especially those with single-cell resolution, it is imperative to develop easy-to-use visualization tools to guide APA analysis. RESULTS: We developed an R package called vizAPA for visualizing APA dynamics from bulk and single-cell data. vizAPA implements unified data structures for APA data and genome annotations. vizAPA also enables identification of genes with differential APA usage across biological samples and/or cell types. vizAPA provides four unique modules for extensively visualizing APA dynamics across biological samples and at the single-cell level. vizAPA could serve as a plugin in many routine APA analysis pipelines to augment studies for APA dynamics. AVAILABILITY AND IMPLEMENTATION: https://github.com/BMILAB/vizAPA.