Activating active motifs in Ni-Fe oxide by introducing dual-defect for oxygen evolution reaction in alkaline seawater.

Developing simple and energy-saving pathways to prepare high-efficient and robust non-noble metal based electrocatalysts remains a huge challenge to hydrogen production from seawater electrolysis. Here we demonstrate a facile hydrothermal-calcination-etching approach that simultaneously achieves the required surface N doping and Fe vacancies generation to activate the Ni-O-Fe active motifs in N-vFe-NiFe2O4/NF. The unique localized environments (Ni-N-Fe structures and unsaturated O- and N-coordination) due to dual-defect strategy can effectively regulate the electronic structure of the Ni-O-Fe motif to make the motif more reactive. As a result, the N-vFe-NiFe2O4/NF catalyst exhibits overpotentials of 210, 213 and 222 mV to deliver 100 mA cm-2 in 1.0 M KOH, simulated seawater and alkaline seawater environments, respectively. Theoretical calculations prove that the Ni-O-Fe structure is the active motif and that the presence of special localized environments can optimize the adsorption of key intermediates on the activated active motifs.

Survey of arsenic content in edible seaweeds and their health risk assessment.

Since humans are especially sensitive to arsenic exposure, predominantly through diet, a strict control of the most widely consumed seaweeds is mandatory. Total arsenic contents and arsenic species in twenty-five different seaweeds from five different origins were studied. Seaweeds selected, included Phaeophyta (brown seaweed), Chlorophyta (green seaweed) and Rhodophyta (red seaweed) genera. The highest arsenic content appears in the Phaeophyta seaweed in the range from 11 to 162 mg kg-1 dried weight. Arsenosugars were found to be the predominant species of arsenic in most seaweeds, being up to 99.7% of total arsenic in some samples. The arsenic dietary intakes for seaweeds studied were assessed and the Target Hazard Quotients (THQ) and the Target Cancer Risk (TCR) were calculated, taking into account inorganic arsenic contents (iAs). iAs species in seaweeds showed low risk of arsenic intake except for Hizikia fusiforme samples.

Strong Interface Coupling Enables Stability of Amorphous Meta-Stable State in CoS/Ni3 S2 for Efficient Oxygen Evolution.

Rational design of heterostructure catalysts through phase engineering strategy plays a critical role in heightening the electrocatalytic performance of catalysts. Herein, a novel amorphous/crystalline (a/c) heterostructure (a-CoS/Ni3 S2 ) is manufactured by a facile hydrothermal sulfurization method. Strikingly, the interface coupling between amorphous phase (a-CoS) and crystalline phase (Ni3 S2 ) in a-CoS/Ni3 S2 is much stronger than that between crystalline phase (c-CoS) and crystalline phase (Ni3 S2 ) in crystalline/crystalline (c/c) heterostructure (c-CoS/Ni3 S2 ) as control sample, which makes the meta-stable amorphous structure more stable. Meanwhile, a-CoS/Ni3 S2 has more S vacancies (Sv ) than c-CoS/Ni3 S2 because of the presence of an amorphous phase. Eventually, for the oxygen evolution reaction (OER), the a-CoS/Ni3 S2 exhibits a significantly lower overpotential of 192 mV at 10 mA cm-2 compared to the c-CoS/Ni3 S2 (242 mV). An exceptionally low cell voltage of 1.51 V is required to achieve a current density of 50 mA cm-2 for overall water splitting in the assembled cell (a-CoS/Ni3 S2 || Pt/C). Theoretical calculations reveal that more charges transfer from a-CoS to Ni3 S2 in a-CoS/Ni3 S2 than in c-CoS/Ni3 S2 , which promotes the enhancement of OER activity. This work will bring into play a fabrication strategy of a/c catalysts and the understanding of the catalytic mechanism of a/c heterostructures.

All layers patterned conical nanostructured thin-film silicon solar cells for light-trapping efficiency improvement.

Thin-film silicon solar cells (TSSC) has received great attention due to its advantages of low cost and eco-friendly. However, traditional single-layer patterned solar cells (SPSC) still fall short in light-trapping efficiency. This article presents an all layers patterned (ALP) conical nanostructured TSSC to enhance the low absorption caused by the thin absorption layers. The Finite-Difference Time-Domain result shows that a photocurrent density up to 41.27 mA/cm2 can be obtained for the structure, which is 31.39% higher than that of the SPSC. An electrical optimization simulation of doping concentration was carried out on the parameters of the optically optimal structure of the model. The power conversion efficiency is 17.15%, which is 1.72 times higher than that of the planar structure. These results demonstrate a success for the potential and prospect of the fully patterned nanostructures in thin-film photovoltaic devices.

A Case of Subglottic Marginal B-Cell Lymphoma With Laryngeal Amyloidosis.

Laryngeal mucosa-associated lymphoid tissue (MALT) is an extra-nodal margin zone B-cell lymphoma (MALT lymphoma) and a low-grade malignant lymphoma with a low incidence, the etiology of the condition remains obscure, and the process of differential diagnosis poses a significant challenge, so it is easy to miss diagnosis and misdiagnosis clinically. The present article presents a clinical case study of a patient who was diagnosed with subglottic MALT lymphoma, which was associated with laryngeal amyloidosis. The patient underwent a successful treatment regimen comprising carbon dioxide laser and radiotherapy. In addition, the article provides an overview of relevant literature that can aid in the diagnosis and management of this rare disease. The study is expected to contribute to the existing body of knowledge on the treatment of subglottic MALT lymphoma and laryngeal amyloidosis.

Anion-induced electronic localization and polarized cobalt clusters for highly efficient water splitting.

It is a promising pathway to use anions to regulate electronic structures, reasonably design and construct highly efficient catalysts for water splitting. Herein, a N-regulated Co cluster catalyst confined in carbon nanotubes, N-Co NCNTs, was constructed successfully. Nitrogen anions played a crucial role in optimizing the electronic structures of Co clusters and enhancing localization of electrons, resulting in polarized cobalt clusters. The N-induced electronic localization and the resulting polarized Co clusters are responsible for the improvement of catalytic activity. N-Co NCNTs exhibited ultra-low overpotentials of 178 mV and 92 mV for the OER and HER to achieve 10 mA cm-2 in an alkaline electrolyte, respectively. Its long-term catalytic durability is mainly attributed to the obstacle to the surface oxidation of Co clusters caused by N-regulation. N-Co NCNTs maintained a stable current density for 160 h at 10 mA cm-2. DFT computations confirmed the decisive role played by nitrogen anions in regulating the electronic structure. This work provides a pathway for understanding and designing highly efficient anion-regulated catalysts.

Capsaicin functions as a selective degrader of STAT3 to enhance host resistance to viral infection.

Although STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1. In VSV-infected mice, pretreatment with capsaicin improved the survival rate and suppressed inflammatory responses accompanied by attenuated VSV replication in the liver, lung, and spleen. The inhibition of viral replication by capsaicin was independent of TRPV1 and occurred mainly at postviral entry steps. We further revealed that capsaicin directly bound to STAT3 protein and selectively promoted its lysosomal degradation. As a result, the negative regulation of STAT3 on the type I IFN response was attenuated, and host resistance to viral infection was enhanced. Our results suggest that capsaicin is a promising small-molecule drug candidate, and offer a feasible pharmacological strategy for strengthening host resistance to viral infection.

Single-cell sequencing of immune cells after marathon and symptom-limited cardiopulmonary exercise.

Vigorous-intensity leisure-time physical activity, such as marathon, has become increasingly popular, but its effect on immune functions and health is poorly understood. Here, we performed scRNA-seq analysis of peripheral blood mononuclear cells (PBMCs) after a bout of symptom-limited cardiopulmonary exercise (CPX) test or marathon. Time-series single-cell analysis revealed the detailed series of landscapes of immune cells in response to short and long vigorous-intensity activities. Reduction of effective T cells was observed with the cell migration and motility pathways enriched in circulation following marathon. Baseline values of PBMCs abundance were reached around 1 h after CPX and 24 h following marathon, but longer time was required for expression recovery of cytotoxicity genes. The ratio of effector/naive T cells was found to change uniformly among the participants and could serve as a better indicator for exercise intensity than the CD4+/CD8+ T cell ratio. Moreover, we identified time-dependent monocyte state transitions after marathon.

Isoliquiritigenin inhibits virus replication and virus-mediated inflammation via NRF2 signaling.

BACKGROUND: The transcription factor NRF2 is a master redox switch that regulates the cellular antioxidant response. However, recent advances have revealed new roles for NRF2, including the regulation of antiviral responses to various viruses, suggesting that pharmacological NRF2-activating agents may be a promising therapeutic drug for viral diseases. Isoliquiritigenin (ISL), a chalcone isolated from liquorice (Glycyrrhizae Radix) root, is reported to be a natural NRF2 agonist and has has antiviral activities against HCV (hepatitis C virus) and IAV (influenza A virus). However, the spectrum of antiviral activity and associated mechanism of ISL against other viruses are not well defined. PURPOSE: This study investigated the antiviral activity and underlying mechanism of ISL against vesicular stomatitis virus (VSV), influenza A virus (H1N1), encephalomyocarditis virus (EMCV), herpes simplex virus type 1 (HSV-1). METHODS: We evaluated the antiviral activity of ISL against VSV, H1N1, EMCV, and HSV-1 using flow cytometry and qRT-PCR analysis. RNA sequencing and bioinformatic analysis were performed to investigate the potential antiviral mechanism of ISL. NRF2 knockout cells were used to investigate whether NRF2 is required for the antiviral activity of ISL. The anti-apoptosis and anti-inflammatory activities of ISL were further measured by counting cell death ratio and assessing proinflammatory cytokines expression in virus-infected cells, respectively. In addition, we evaluated the antiviral effect of ISL in vivo by measuring the survival rate, body weights, histological analysis, viral load, and cytokine expression in VSV-infected mouse model. RESULTS: Our data demonstrated that ISL effectively suppressed VSV, H1N1, HSV-1, and EMCV replication in vitro. The antiviral activity of ISL could be partially impaired in NRF2-deficient cells. Virus-induced cell death and proinflammatory cytokines were repressed by ISL. Finally, we showed that ISL treatment protected mice against VSV infection by reducing viral titers and suppressing the expression of inflammatory cytokines in vivo. CONCLUSION: These findings suggest that ISL has antiviral and anti-inflammatory effects in virus infections, which are associated with its ability to activate NRF2 signaling, thus indicating that ISL has the potential to serve as an NRF2 agonist in the treatment of viral diseases.

Phytochemical-Rich Colored Noodles Fortified with an Aqueous Extract of Clitoria ternatea Flowers.

Clitoria ternatea (CT) flowers are rich in phytochemicals. An innovative approach was taken to utilize CT flower extract (CTFE) as a functional ingredient with natural pigment by incorporating it into noodles. The aim of this study was to examine the effect of the CTFE amount (0-30%) on the color, texture, phytochemicals, and sensory quality of both dried and cooked noodles. Dried noodles with 30% CTFE had the highest total anthocyanins (9.48 µg/g), polyphenols (612 µg/g), DPPH radical scavenging capacity (165 µg TE/g), and reducing power (2203 µg TE/g). Cooking resulted in a significant decrease in the anthocyanin levels and blue color, while also increasing the greenness of the noodle. Both dried and cooked noodles with 20-30% CTFE showed a significantly higher color preference compared to the control sample. Despite a significant reduction in the cutting force, tensile strength, and extensibility of cooked noodles with 20-30% CTFE, the sensory attributes such as flavor, texture, and overall preferences were similar to those of noodles with 0-30% CTFE. Blue noodles with high phytochemicals, antioxidant activities, and desirable sensory qualities can be produced by the incorporation of 20-30% CTFE.

Scale Difference from the Impact of Disease Control on Pig Production Efficiency.

Epidemic disease prevention plays a critical role in ensuring the healthy development of livestock farming, and the subjective willingness of breeders can be affected by the cost of epidemic disease prevention. To correct the misconception that farmers regard the cost of disease control as an ineffective cost, and to promote the healthy development of the pig breeding industry, our study employed the data envelopment analysis super-efficiency model and panel threshold regression model to evaluate the combination of the cost of epidemic disease prevention and swine productivity using data collected from 1998-2018 across 30 provinces in China. The following results were obtained. (1) The cost of epidemic disease prevention generated a non-linear on swine productivity when the swine farming scale was limited; (2) When the number of animals at the beginning of the year was less than 6.0002, swine productivity was impacted negatively; (3) When the number of animals at the beginning of the year ranged between 6.0002 and 12.9994, the impact was insignificant; (4) A strong correlation was observed between the expenses of epidemic disease prevention and animal productivity when the number of animals at the beginning of the year exceeded 12.9994. These results indicate that publicity should be enhanced to elucidate the combination of epidemic disease prevention and swine productivity among breeders. In addition, the government should introduce relevant policies to encourage the development of large-scale pig farming, such as subsidies for the construction of large-scale farms and insurance.

The Protective Role of Bmal1-Regulated Autophagy Mediated by HDAC3/SIRT1 Pathway in Myocardial Ischemia/Reperfusion Injury of Diabetic Rats.

PURPOSE: Histone deacetylase 3 (HDAC3) and silent information regulator 1 (SIRT1) are histone deacetylases that regulate important metabolic pathways and play important roles in diabetes and myocardial ischemia/reperfusion (IR) injury. In this study, we explored the protective mechanism of Bmal1-regulated autophagy mediated by the HDAC3/SIRT1 pathway in myocardial IR injury of diabetic rats. METHODS AND RESULTS: Type 1 diabetes was established by administering an intraperitoneal injection of streptozotocin. After 8 weeks, the left anterior descending coronary artery was ligated for 30 min and reperfused for 120 min to establish a myocardial IR injury model in diabetic rats. H9c2 cardiomyocytes were exposed to high glucose concentration (30 mM) and hypoxia/reoxygenation (H/R) stimulation in vitro. The myocardial infarct size and levels of serum cTn-I, CK-MB, and LDH in diabetic rats subjected to myocardial IR injury were significantly higher. Upregulated HDAC3 and downregulated SIRT1 expression were observed in diabetic and IR hearts, along with a lower Bmal1 level. Autophagy was rapidly increased in the hearts of diabetic or non-diabetic rats in the IR group compared with the sham group, but significantly attenuated in the hearts of diabetic rats compared with the hearts of non-diabetic rats after IR insult. Consistent with decreased autophagy, we observed increased HDAC3 expression and decreased SIRT1 and Bmal1 levels in the myocardial tissue of diabetic rats after IR. Inhibition of HDAC3 by the inhibitor RGFP966 and activation of SIRT1 by the agonist SRT1720 could significantly attenuate myocardial IR injury in diabetic rats by restoring Bmal1-regulated autophagy. CONCLUSION: Based on these findings, the disordered HDAC3/SIRT1 circuit (upregulated HDAC3 and downregulated SIRT1 levels) plays an important role in aggravating myocardial IR injury in diabetic rats by downregulating Bmal1-mediated autophagy. Treatments targeting HDAC3/SIRT1 to activate the autophagy may represent a novel strategy to alleviate myocardial IR injury in diabetes.

The influence mechanism of the relationship between entrepreneurial learning and entrepreneurial intention.

Based on relevant literature, this study adopted entrepreneurial learning theory to construct a relationship model between entrepreneurial learning and entrepreneurial intention. In this framework, entrepreneurial learning was divided into three dimensions: entrepreneurial education learning, experiential learning, and social network learning. A questionnaire survey was conducted among 1,399 undergraduate students in Zhejiang Province to investigate how entrepreneurial learning influenced entrepreneurial intention, while considering the mediating effect of entrepreneurial self-efficacy. This empirical research found that: (1) experiential learning and social network learning had significant positive impacts on entrepreneurial intention, but there was no significant relationship between entrepreneurial education learning and entrepreneurial intention; (2) entrepreneurship education learning and social network learning had significant positive relationships with entrepreneurial self-efficacy, but experiential learning had a significant negative relationship with entrepreneurial self-efficacy; and (3) entrepreneurial self-efficacy partially mediated the relationship between experiential learning, social network learning, and entrepreneurial intention, and fully mediated the relationship between entrepreneurial education learning and entrepreneurial intention. These findings suggest that colleges and universities in China could broaden entrepreneurial learning and strengthen social network learning.

Global, regional, and national burden of ovarian cancer and the attributable risk factors in all 194 countries and territories during 2007-2017: A systematic analysis of the Global Burden of Disease Study 2017.

BACKGROUND: We estimated the global burden of ovarian cancer (OC) in 194 countries and territories between 2007 and 2017. METHODS: Data were extracted from the Global Burden of Disease (GBD), Injuries, and Risk Factors 2017 study. RESULTS: Globally, 286 126.80 (95% UI = 278 075.38-295 311.41) incident cases, 4.67 million (4.53-4.83) disability-adjusted life-years (DALYs), and 175 981.99 (171 384.15-181 198.43) deaths were reported in 2017. The age-standardized incidence and DALY rates increased by 2.05% and 1.34% during 2007-2017, respectively, while the age-standardized mortality rate decreased by -0.14%. The age-standardized incidence, DALY, and mortality rates in 2017 were the highest in the high socio-demographic index (SDI) quintile, but the largest percentage increase during 2007-2017 was in the low-SDI quintile. Among regions, Central Europe showed the highest 2017 age-standardized incidence, DALY, and mortality rates, whereas South Asia and East Asia showed the largest percentage increases in both rates during 2007-2017. Among countries, India showed the largest percentage increase in age-standardized incidence and DALY rates, whereas Iran showed the largest percentage increase in age-standardized mortality rates. Globally, the largest percentage increase in risk-attributable DALYs was associated with metabolic risk factors (e.g., high fasting plasma glucose levels). CONCLUSION: The global age-standardized incidence, DALYs, and mortality rates of OC remain stable during 2007-2017. However, the low SDI quintile and the greatest burden in South and East Asia, India, and Iran suggested that more targeted strategies should be performed in those regions and countries.

Experimental noise and vibration characteristics of elevated urban rail transit considering the effect of track structures and noise barriers.

Vibration of the elevated urban rail transit (URT) severely affects the health of nearby residents, threatens the integrity of adjacent historic buildings, and aggravates the performance of vibration-sensitive instruments in buildings, and the accompanied annoying structure-borne noise always arouses public complaint. Vibration and noise mitigation measures through track structures and/or noise barriers are increasingly favored to deal with these challenging issues. This paper presents systematic field measurements on noise and vibrations of elevated URT. The vibration experiment covers vibration of track structures, bridge girders and piers, and ground soil under three different track structures, i.e., embedded sleeper track, ladder sleeper track, and floating slab track (FST) with rubber mats. Noise measurements were also conducted considered the effect of track structures and with or without fully enclosed noise barriers. It is shown that ladder sleeper track and FST were more effective in control bridge vibration than ground vibration. The overall vibration level of the bridge is 8~10 dB greater than the ground vibrations. The noise reduction effect through track structure was limited for far-field ground. Furthermore, it is found that the noise barrier was more effective to reduce near-field wheel/rail rolling noise rather than far-field noise. Good correlation between structure-borne noise and vibration was observed for both the embedded sleeper track and FST at the bottom slab of the box girder bridge.

Simplified plasmid cloning with a universal MCS design and bacterial in vivo assembly.

BACKGROUND: The ability to clone DNA sequences quickly and precisely into plasmids is essential for molecular biology studies. The recent development of seamless cloning technologies has made significant improvements in plasmid construction, but simple and reliable tools are always desirable for time- and labor-saving purposes. RESULTS: We developed and standardized a plasmid cloning protocol based on a universal MCS (Multiple Cloning Site) design and bacterial in vivo assembly. With this method, the vector is linearized first by PCR (Polymerase Chain Reaction) or restriction digestion. Then a small amount (10 ~ 20 ng) of this linear vector can be mixed with a PCR-amplified insert (5× molar ratio against vector) and transformed directly into competent E. coli cells to obtain the desired clones through in vivo assembly. Since we used a 36-bp universal MCS as the homologous linker, any PCR-amplified insert with ~ 15 bp compatible termini can be cloned into the vector with high fidelity and efficiency. Thus, the need for redesigning insert-amplifying primers according to various vector sequences and the following PCR procedures was eliminated. CONCLUSIONS: Our protocol significantly reduced hands-on time for preparing transformation reactions, had excellent reliability, and was confirmed to be a rapid and versatile plasmid cloning technique. The protocol contains mostly mixing steps, making it an extremely automation-friendly and promising tool in modern biology studies.

Dysregulation of miR-637 is involved in the development of retinopathy in hypertension patients and serves a regulatory role in retinol endothelial cell proliferation.

BACKGROUND: MicroRNAs (miRNAs) play an important role in the proliferation and migration of retinal endothelial cells in patients with hypertension and hypertensive retinopathy (HR). This study aimed to investigate the clinical value of miR-637 in HR and its role in retinal endothelial cell proliferation and migration. METHODS: A total of 126 subjects were recruited for the study, including 42 patients with hypertension (male/female 25/17), 42 healthy individuals (male/female 20/22), and 42 cases with HR (male/female 20/22). Except SBP and DBP, there was no significant difference in other indexes among the three groups. qRT-PCR was used to detect the expression of miR-637. The receiver operating curve (ROC) was used for diagnosis value analysis. Logistic regression analysis was used to evaluate the relationship between miR-637 and HR. CCK-8 and Transwell were used to detect the effect of miR-637 on the proliferation and migration of HUVECs. RESULTS: Compared with hypertensive patients, HR patients had the lowest expression of miR-637. The area under the curve (AUC) of miR-637 detected by the ROC curve method is 0.892, which has the ability to distinguish hypertension and HR patients. Logistic regression analysis showed that miR-637 was an independent influence factor in HR. Cell experiment results showed that overexpression of miR-637 significantly inhibited cell proliferation and migration, while downregulation of miR-637 had the opposite effect. Luciferase analysis showed that STAT3 was the target gene of miR-637. CONCLUSION: Our data indicate that miR-637 is a potential non-invasive marker for patients with HR. The action of miR-637 on STAT3 may inhibit the proliferation and migration of retinal endothelial cells, providing a possible target for the treatment of HR.

Roles of HDAC3-orchestrated circadian clock gene oscillations in diabetic rats following myocardial ischaemia/reperfusion injury.

The circadian clock is closely related to the development of diabetes mellitus and cardiovascular disease, and disruption of the circadian clock exacerbates myocardial ischaemia/reperfusion injury (MI/RI). HDAC3 is a key component of the circadian negative feedback loop that controls the expression pattern of the circadian nuclear receptor Rev-erbα to maintain the stability of circadian genes such as BMAL1. However, the mechanism by which the HDAC3-orchestrated Rev-erbα/BMAL1 pathway increases MI/RI in diabetes and its relationship with mitophagy have yet to be elucidated. Here, we observed that the clock genes Rev-erbα, BMAL1, and C/EBPß oscillations were altered in the hearts of rats with streptozotocin (STZ)-induced diabetes, with upregulated HDAC3 expression. Oscillations of Rev-erbα and BMAL1 were rapidly attenuated in diabetic MI/R hearts versus non-diabetic I/RI hearts, in accordance with impaired and rhythm-disordered circadian-dependent mitophagy that increased injury. Genetic knockdown of HDAC3 significantly attenuated diabetic MI/RI by mediating the Rev-erbα/BMAL1 circadian pathway to recover mitophagy. Primary cardiomyocytes with or without HDAC3 siRNA and Rev-erbα siRNA were exposed to hypoxia/reoxygenation (H/R) in vitro. The expression of HDAC3 and Rev-erbα in cardiomyocytes was increased under high-glucose conditions compared with low-glucose conditions, with decreased BMAL1 expression and mitophagy levels. After H/R stimulation, high glucose aggravated H/R injury, with upregulated HDAC3 and Rev-erbα expression and decreased BMAL1 and mitophagy levels. HDAC3 and Rev-erbα siRNA can alleviate high glucose-induced and H/R-induced injury by upregulating BMAL1 to increase mitophagy. Collectively, these findings suggest that disruption of HDAC3-mediated circadian gene expression oscillations induces mitophagy dysfunction, aggravating diabetic MI/RI. Cardiac-specific HDAC3 knockdown could alleviate diabetic MI/RI by regulating the Rev-erbα/BMAL1 pathway to restore the activation of mitophagy.

Gastrointestinal Symptoms Associated With Unfavorable Prognosis of COVID-19 Patients: A Retrospective Study.

Background and Aim: The global pandemic of COVID-19 has posed an enormous threat to the economy and people's lives across various countries. Patients with COVID-19 most commonly present with respiratory symptoms. However, gastrointestinal (GI) symptoms can also occur. We aimed to study the relationship between GI symptoms and disease prognosis in patients with COVID-19. Methods: In a single-center and retrospective cohort study, the outcomes in COVID-19 patients with or without GI symptoms were compared. The propensity score is a conditional probability of having a particular exposure (COVID-19 patients with GI symptoms vs. without GI symptoms) given a set of baseline measured covariates. Survival was estimated using the Kaplan-Meier method, and any differences in survival were evaluated with a stratified log-rank-test. To explore the GI symptoms associated with ARDS, non-invasive ventilator treatment, tracheal intubation, tracheotomy, and CRRT, univariable and multivariable COX regression models were used. Results: Among 1,113 eligible patients, 359 patients with GI symptoms and 718 without GI symptoms had similar propensity scores and were included in the analyses. Patients with GI symptoms, as compared with those without GI symptoms, were associated with a similar risk of death, but with higher risks of ARDS, non-invasive mechanical ventilation in COVID-19 patients, respectively. Conclusions: The presence of GI symptoms was associated with a high risk of ARDS, non-invasive mechanical ventilation and tracheal intubation in patients with COVID-19 but not mortality.

Indoxyl sulfate induces intestinal barrier injury through IRF1-DRP1 axis-mediated mitophagy impairment.

Rationale: The dysfunctional gut-kidney axis forms a vicious circle, which eventually becomes a catalyst for the progression of chronic kidney disease (CKD) and occurrence of related complications. However, the pathogenic factors of CKD-associated intestinal dysfunction and its mechanism remain elusive. Methods: We first identified the protein-bound uremic toxin indoxyl sulfate (IS) as a possible contributor to intestinal barrier injury. Transepithelial electrical resistance, permeability assay and transmission electron microscopy were carried out to evaluate the damaging effect of IS on intestinal barrier in intestinal epithelial cells, IS-injected mice and CKD mice. In vitro and in vivo experiments were performed to investigate the role of IS in intestinal barrier injury and the underlying mechanism. Finally, CKD mice treated with AST-120 (an oral adsorbent for IS) and gene knockout mice were used to verify the mechanism and to explore possible interventions for IS-induced intestinal barrier injury. Results: Transepithelial electrical resistance and the expressions of tight junction-related genes were significantly suppressed by IS in intestinal epithelial cells. In vitro experiments demonstrated that IS inhibited the expression of dynamin-related protein 1 (DRP1) and mitophagic flux, whereas DRP1 overexpression attenuated IS-induced mitophagic inhibition and intestinal epithelial cell damage. Furthermore, IS suppressed DRP1 by upregulating the expression of interferon regulatory factor 1 (IRF1), and IRF1 could directly bind to the promoter region of DRP1. Additionally, the decreased expression of DRP1 and autophagosome-encapsulated mitochondria were observed in the intestinal tissues of CKD patients. Administration of AST-120 or genetic knockout of IRF1 attenuated IS-induced DRP1 reduction, mitophagic impairment and intestinal barrier injury in mice. Conclusions: These findings suggest that reducing IS accumulation or targeting the IRF1-DRP1 axis may be a promising therapeutic strategy for alleviating CKD-associated intestinal dysfunction.