Glycyrrhizic acid improves tacrolimus-induced renal injury by regulating autophagy.

Tacrolimus (TAC)-induced renal injury is detrimental to long-term kidney function, but a treatment medication is not available. Glycyrrhizic acid (GA) is an active ingredient in licorice widely used to treat kidney disease. Thus, this study explored the mechanisms of renoprotection by GA on TAC-induced renal injury. C57BL/6 mice were subjected daily to TAC or a combination of TAC and GA for 4 weeks, and then renal function, histopathology, and autophagy were assessed to examine the effect of GA on a renal injury. Next, Human kidney proximal tubular epithelial (HK-2) cells were pretreated with GA for 2 h and then treated with TAC for 24 h. The effect of GA on TAC-induced HK-2 cell injury was assessed by measuring cell viability, apoptosis, autophagy, and lysosomes. Mice exposed to TAC and treated with GA had significantly greater improvements in renal function and tubulointerstitial fibrosis in comparison to mice not treated with GA. In addition, fibrosis-related protein expression, including α-smooth muscle actin and fibronectin, decreased after GA treatment. GA treatment also relieved autophagic clearance in TAC-induced renal injury. Several in vitro studies found that TAC inhibited cell viability, autophagy, lysosomal acidification, and promoted apoptosis. However, these results were less pronounced with GA pretreatment. In addition, bafilomycin A1 (which inhibits lysosomal function) reduced the protective effect of GA, indicating that lysosomal function plays an important role in this effect. Our data suggest that GA improves lysosomal function and regulates autophagy to protect against TAC-induced renal injury.

Egg White Protein-Proanthocyanin Complexes Stabilized Emulsions: Investigation of Physical Stability, Digestion Kinetics, and Free Fatty Acid Release Dynamics.

Egg white proteins pose notable limitations in emulsion applications due to their inadequate wettability and interfacial instability. Polyphenol-driven alterations in proteins serve as an effective strategy for optimizing their properties. Herein, covalent and non-covalent complexes of egg white proteins-proanthocyanins were synthesized. The analysis of structural alterations, amino acid side chains and wettability was performed. The superior wettability (80.00° ± 2.23°) and rigid structure (2.95 GPa) of covalent complexes established favorable conditions for their utilization in emulsions. Furthermore, stability evaluation, digestion kinetics, free fatty acid (FFA) release kinetics, and correlation analysis were explored to unravel the impact of covalent and non-covalent modification on emulsion stability, dynamic digestion process, and interlinkages. Emulsion stabilized by covalent complex exhibited exceptional stabilization properties, and FFA release kinetics followed both first-order and Korsmeyer-Peppas models. This study offers valuable insights into the application of complexes of proteins-polyphenols in emulsion systems and introduces an innovative approach for analyzing the dynamics of the emulsion digestion process.

One-Stop Extraction and In Situ RT-qPCR for Ultrasensitive Detection of Highly Diluted SARS-CoV-2 in Large-Volume Samples from Aquatic Environments.

Surveillance of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in aquatic environments attracted attention due to its considerable impacts on human health and ecology, especially in countries with poor sanitation standards. Based on a strategy of one-stop extraction and in situ amplification, we developed an ultrasensitive method that uses a polyacrylamide derivative-modified filter disc (PAD-FD), in which highly diluted RNA can be efficiently concentrated onto the filter disc and directly used for amplification. A newly designed spin column with a cup-like filter base facilitated the non-contact transfer of the affinity filter disc from the column to a PCR tube. The limit of detection of the PAD-FD coupled with RT-qPCR is 10 copies/mL. Using 32 suspected SARS-CoV-2 samples, we demonstrated that the detection rate of our method (62.5%, 20/32) was triple the rate of the commercial kit (18.8%, 6/32). Using a PAD-FD, 56.3% (18/32) and 40.6% (13/32) of the 10-fold-dilution samples with river and tap water, respectively, were detected. Even when diluted 100-fold, 28.1% (9/32) and 37.5% (12/32) were still detected in river and tap water, respectively. We believe that the PAD-FD method offers an accurate testing tool for monitoring viral RNA in aquatic environments, contributing to the forewarning of the SARS-CoV-2 outbreak and the breaking of the transmission chain.

Tweezer PCR: A Highly Specific Method for Accurate Identification of Low-Abundance Mutations.

Somatic mutation is a valuable biomarker for tracking tumor progression and migration due to its distinctive feature in various tumors and its wide distribution throughout body fluids. However, accurately detecting somatic mutations from the abundant DNA of noncancerous origins remains a practical challenge in the clinic. Herein, we developed an ultraspecific method, called tweezer PCR, for detecting low-abundance mutations inspired by the design of DNA origami. The high specificity of tweezer PCR relies on a tweezer-shaped primer containing six basic functional units: a primer, a hairpin, a linker, a blocker, a spacer, and a toehold. After optimizing the structure of the tweezer-shaped primer and enhancing its specificity by adding additional Mg2+ and Na+, tweezer PCR distinguished as low as 20 copies of mutations from 2 million copies of wild-type templates per test. By testing synthesized plasmids and plasma samples gathered from nonsmall-cell lung cancer patients, tweezer PCR showed higher specificity and robustness for detecting low-copy-number mutations in contrast with digital droplet PCR. Additionally, the need for conventional instruments makes tweezer PCR a practically accessible method for testing low-abundance mutations. Because of its numerous advantages, we believe that tweezer PCR offers a precise, robust, and pragmatic tool for cancer screening, prognosis, and genotyping in the clinic.

Palmitoylation landscapes across human cancers reveal a role of palmitoylation in tumorigenesis.

BACKGROUND: Protein palmitoylation, which is catalyzed by palmitoyl-transferase and de-palmitoyl-transferase, plays a crucial role in various biological processes. However, the landscape and dynamics of protein palmitoylation in human cancers are not well understood. METHODS: We utilized 23 palmitoyl-acyltransferases and seven de-palmitoyl-acyltransferases as palmitoylation-related genes for protein palmitoylation analysis. Multiple publicly available datasets were employed to conduct pan-cancer analysis, examining the transcriptome, genomic alterations, clinical outcomes, and correlation with c-Myc (Myc) for palmitoylation-related genes. Real-time quantitative PCR and immunoblotting were performed to assess the expression of palmitoylation-related genes and global protein palmitoylation levels in cancer cells treated with Myc depletion or small molecule inhibitors. Protein docking and drug sensitivity analyses were employed to predict small molecules that target palmitoylation-related genes. RESULTS: We identified associations between palmitoylation and cancer subtype, stage, and patient survival. We discovered that abnormal DNA methylation and oncogenic Myc-driven transcriptional regulation synergistically contribute to the dysregulation of palmitoylation-related genes. This dysregulation of palmitoylation was closely correlated with immune infiltration in the tumor microenvironment and the response to immunotherapy. Importantly, dysregulated palmitoylation was found to modulate canonical cancer-related pathways, thus influencing tumorigenesis. To support our findings, we performed a proof-of-concept experiment showing that depletion of Myc led to reduced expression of most palmitoylation-related genes, resulting in decreased global protein palmitoylation levels. Through mass spectrometry and enrichment analyses, we also identified palmitoyl-acyltransferases ZDHHC7 and ZDHHC23 as significant contributors to mTOR signaling, DNA repair, and immune pathways, highlighting their potential roles in tumorigenesis. Additionally, our study explored the potential of three small molecular (BI-2531, etoposide, and piperlongumine) to modulate palmitoylation by targeting the expression or activity of palmitoylation-related genes or enzymes. CONCLUSIONS: Overall, our findings underscore the critical role of dysregulated palmitoylation in tumorigenesis and the response to immunotherapy, mediated through classical cancer-related pathways and immune cell infiltration. Additionally, we propose that the aforementioned three small molecule hold promise as potential therapeutics for modulating palmitoylation, thereby offering novel avenues for cancer therapy.

Liraglutide abrogates nephrotoxic effects of chemotherapies.

Acute kidney injury (AKI) is a common clinical complication. Cisplatin (Cis) is an effective chemotherapeutic drug; however, its acute nephrotoxicity often limits its application. The role of liraglutide (Lir), an agonist of the glucagon-like peptide-1 receptor (GLP-1R), has recently attracted increasing attention beyond glycemic regulation. This study showed that Lir significantly ameliorated Cis-induced kidney dysfunction and renal damage. However, this renoprotective effect was partially abolished in GLP-1R knockout (GLP-1R-/-) mice. Furthermore, we synthesized Lir metabolites, GLP-1 (9-37) and GLP-1 (28-37), and found that they also exerted reno-protective effects that were not impaired in GLP-1R-/- mice. We also demonstrated that Lir and its metabolites reduced cisplatin-induced apoptosis in human renal tubular epithelial cells (HK-2). After silencing GLP-1R expression in HK-2 cells with small interfering ribose nucleic acid (siRNA), the protective effect of Lir on HK-2 cells was inhibited, while the protective effects of GLP-1 (9-37) and GLP-1 (28-37) were not affected. Additionally, we demonstrated that Lir and its metabolites inhibited Cis-induced high-mobility group box 1 (HMGB1) nuclear-cytoplasmic translocation and release, and reduced inflammatory cytokines and HMGB1 receptor expression. The exogenous use of recombinant HMGB1 (rHMGB1) dramatically weakened the protective effects of Lir and its metabolites. In conclusion, our study shows that Lir significantly attenuated Cis-induced AKI through GLP-1R dependent and independent pathways, mediated by inhibiting nuclear-cytoplasmic translocation and release of HMGB1. Lir and its metabolites may be effective drugs for treating cisplatin-induced nephrotoxicity.

Pharmacological targeting macrophage phenotype via gut-kidney axis ameliorates renal fibrosis in mice.

Renal fibrosis is a non-negligible pathological change in chronic kidney disease (CKD). Increasing evidence indicates that macrophage and gut-kidney axis are correlated with CKD. In this study, we manifest that pharmacological modulating macrophage phenotype via gut-kidney axis is conducive to the alleviation of renal fibrosis. Employing wild-type male mice with unilateral ureteral obstruction (UUO), renal fibrosis was dramatically mitigated in mice treated with antibiotics. And antibiotics application restricted the synthesis of intestinal flora metabolite Trimethylamine N-Oxide (TMAO). However, a 1.3% choline diet enhanced fibrosis. Then we further examined macrophage phenotype through the gut-kidney axis. In in vivo and in vitro culture experiments, the mRNA expression of Nos2, Tnf-α, Il-6, and Il-1ß increased under TMAO stimulation. Curbing the NLRP3 inflammasome countered TMAO-induced M1 polarization in bone marrow-derived macrophages. This finding demonstrates that NLRP3 plays a critical part in macrophage polarization. Because of the declining M1 polarization trend in the early stage, M2 macrophages undoubtedly decreased in the tissues. Our results revealed that some metabolites could regulate macrophage phenotype, which matters the severity of renal fibrosis. Thus, pharmacological targeting macrophage phenotype via gut-kidney axis may be a different strategy to treat renal fibrosis.

Anionic Polysaccharide-Modified Filter Papers for Rapid Isolation of Extracellular Vesicles from Diverse Samples in a Simple Bind-Wash-Elute Manner.

Extracellular vesicles (EVs) play a significant role in the pathophysiological process of many diseases, highlighting their values in medical diagnosis and disease monitoring. However, the current EV isolation methods are time-consuming, inconvenient to operate, and incompatible with downstream analyses. Here, we present a novel isolation method employing anionic polysaccharide-modified filter papers for the isolation of EVs (AppiEV) via electrostatic adsorption. A disc of glass fiber-based filter modified with sodium alginate was assembled into a spin column to function as the solid capture phase. In the acidic condition, EVs were induced to carry more positively charged ions, which enable the capture of EVs by the negatively charged filter paper. After a wash, the EVs were released from the spin column using an alkaline elution buffer, which induces the EVs to carry more negative charges. The EVs isolated by AppiEV from cell culture supernatants, plasma, and urine are similar to or even better than those isolated by ultracentrifugation in terms of EV size distribution, protein distribution, and nucleic acid contents. Due to the interference removal of the EV-free RNA and DNA attributed to the negatively charged capture medium, the eluate of AppiEV could be directly used for genetic analysis, including the stem-loop RT-PCR analysis of miR-21 and the allele-specific PCR analysis of mutation genes of EGFR p.L858R and EGFR p.T790M. We believe that AppiEV offers a simple and efficient approach for the isolation of high-quality EVs from various liquid specimens.

Spectral-dependent electronic-photonic modeling of high-speed VCSEL-MMF links for optimized launch conditions.

We present spectral-dependent electronic-photonic modeling of vertical-cavity surface-emitting laser (VCSEL)-multimode fiber (MMF) links for next-generation high-speed interconnects. The beam coupling processes, between the VCSEL and the MMF and between the MMF and the photodetector (PD), are discussed, with spectral-dependent three-dimensional launch conditions analyzed. The model accounts for fiber effects on the transmission performance, specifically modal attenuation, dispersion, mode mixing, and mode partition noise. An advanced split-step small-segment (4-S) method simulates the signal evolution over the MMF with high accuracy and high efficiency. Experimental validation at 25 Gbps confirms the high accuracy of the VCSEL-MMF link model. The model reveals that larger radial offsets can further excite lower-order mode groups reducing the power distributed to higher-order groups when a tilted beam couples to the input fiber facet. With an optimized misalignment launch, the modal bandwidth is greatly improved by 3.8-fold compared to the conventional center launch. The model helps determine the optimum launch condition to improve link performance metrics such as transmission reach.

"Sample-to-Answer" Detection of Rare ctDNA Mutation from 2 mL Plasma with a Fully Integrated DNA Extraction and Digital Droplet PCR Microdevice for Liquid Biopsy.

The "sample-to-answer" integration and automation of circulating tumor DNA (ctDNA)-based liquid biopsy using digital PCR (dPCR) has been hampered by the complicated operations of liquids with volumes ranging from milliliter samples to nanoliter droplets. On the basis of a "3D extensible" design paradigm proposed previously, an integrated droplet digital PCR (IddPCR) microdevice was successfully developed to automate the entire process of liquid biopsy, from the extraction of ctDNA in 2 mL of plasma using magnetic beads to the generation, amplification, and screening of over 30 000 droplets for detection. A series of reagent mixing structures, including macro-, meso-, and micromixers, was designed to enable efficient reagent handling and mixing at different volume scales. The volume thresholds of the microscale and macroscale in the IddPCR device were calculated to be 40 and 100 µL, respectively, based on the fluid dynamics and sizes of the device structures, so that different mixers can be selected according to the reagent volumes. The DNA extraction efficiency obtained on the device was determined to be ∼60%, and the on-chip ddPCR demonstrated a high correlation with an R2 of 0.9986 between the readouts and the estimations by a Poisson distribution. Finally, the IddPCR microdevice was able to detect rare tumor mutations (T790M) with an occurring frequency as low as ∼1% from 2 mL of human plasma in a "sample-to-answer" manner. This work offers a feasible solution for the automation of liquid biopsy and paves the way for its broad applications in clinics.

The glucagon-like peptide-1 (GLP-1) analog liraglutide attenuates renal fibrosis.

Renal fibrosis is recognized as the common route of all chronic kidney disease (CKD) progressing to end-stage renal disease (ESRD). Additionally, accumulating evidence suggests that epithelial-mesenchymal transition (EMT) plays a significant role in the process of renal fibrogenesis. Liraglutide is a long-acting glucagon-like peptide-1 (GLP-1) analog that has been widely used to treat type 2 diabetes. Recent studies have demonstrated that the GLP-1 analogs could also exert protective effects in cardiac fibrosis models. However, the effects of liraglutide on the progression of CKD remain largely unknown. In the present study, we investigated the effects of liraglutide on the progression to renal fibrosis induced by unilateral ureteral obstruction (UUO) and EMT of rat renal tubular epithelial cells (NRK-52E) induced with recombinant transforming growth factor-beta 1 (TGF-ß1). The results indicated that UUO increased collagen deposition and the mRNA expression of fibronectin (FN) and collagen type I alpha 1 (Col1α1) in the obstructed kidney tissues. The effects were blunted in liraglutide-treated UUO mice compared with control mice. The upregulation of Snail1 and alpha smooth muscle actin (α-SMA), and downregulation of E-cadherin revealed that EMT occurred in the UUO kidneys, and these effects were ameliorated following liraglutide treatment. Additionally, liraglutide treatment decreased the expression of TGF-ß1 and its receptor (TGF-ß1R) and inhibited the activation of its downstream signaling molecules (pSmad3 and pERK1/2). The in vitro results showed that the EMT and extracellular matrix (ECM) secretion of NRK-52E cells were induced by TGF-ß1. In addition, the Smad3 and ERK1/2 signaling pathways were highly activated in cells cultured with TGF-ß1. All these effects were attenuated by liraglutide treatment. However, the protective effects of liraglutide were abolished by co-incubation of the GLP-1 receptor (GLP-1R) antagonist exendin-3 (9-39). These results suggest that liraglutide attenuates the EMT and ECM secretion of NRK-52E cells induced by TGF-ß1 and EMT and renal fibrosis induced by UUO. The potential mechanism involves liraglutide binding to and activating GLP-1R, which prevents EMT by inhibiting the activation of TGF-ß1/Smad3 and ERK1/2 signaling pathways, thereby decreasing the ECM secretion and deposition. Therefore, liraglutide is a promising therapeutic agent that may halt the progression of renal fibrosis.

Integrated Graphene Oxide Purification-Lateral Flow Test Strips (iGOP-LFTS) for Direct Detection of PCR Products with Enhanced Sensitivity and Specificity.

An integrated graphene oxide purification-lateral flow test strip (iGOP-LFTS) was developed for on-strip purifying and visually detecting polymerase chain reaction (PCR) products with an improved sensitivity as well as a more stringent specificity. PCR products amplified with a pair of biotin- and digoxin-labeled primers were directly pipetted onto GO pads, on which graphene oxide selectively adsorbed residual primers and primer-dimers with the aid of a running buffer containing MgCl2 and Tween 20. By stacking up three GO pads to increase the surface area for adsorption, 83.4% of double-stranded DNA with a length of 30 bp and 98.6% of 20-nt primers could be removed from a 10-µL DNA mixture. Since no primers interfered with detection, the increase of the sample loading volume from 5 to 20 µL could improve the signal-to-noise ratio of the test line 1.6 fold using the iGOP-LFTS while no changes were observed using the conventional LFTS. The limit of detection of the iGOP-LFTS was determined to be 30 copies of bacteriophage λ-DNA with naked eyes and this limit could be further decreased to 3 copies by loading 20 µL of the sample, which corresponded to a 1000-fold improvement compared to that of the LFTS detected by naked eyes. When the ImageJ analysis was employed, a 100-fold decrease of the detection limit can be obtained. In addition, due to the removal of the primer-dimers, the dim test line observed in the negative control of the LFTS was eliminated using the iGOP-LFTS. A mock clinical specimen spiked with defective HIV-1 (human immunodeficiency virus) viruses was successfully analyzed using a two-step reverse transcription-PCR with 30 amplification cycles followed by the iGOP-LFTS detection. These significant improvements were achieved without introducing any additional hands-on operations and instrumentations.

Enhancing Li-S Battery Performance with Limiting Li[N(SO2F)2] Content in a Sulfolane-Based Sparingly Solvating Electrolyte.

By enhancing the stability of the lithium metal anode and mitigating the formation of lithium dendrites through electrolyte design, it becomes feasible to extend the lifespan of lithium-sulfur (Li-S) batteries. One widely accepted approach involves the utilization of Li[N(SO2F)2] (Li[FSA]), which holds promise in stabilizing the lithium anode by facilitating the formation of an inorganic-dominant solid electrolyte interface (SEI) film. However, the use of Li[FSA] encounters limitations due to inevitable side reactions between lithium polysulfides (LiPSs) and [FSA] anions. In this study, our focus lies in precisely controlling the composition of the SEI film and the morphology of the deposited lithium, as these two critical factors profoundly influence lithium reversibility. Specifically, by subjecting an initial charging process to an elevated temperature, we have achieved a significant enhancement in lithium reversibility. This improvement is accomplished through the employment of a LiPS sparingly solvating electrolyte with a restricted Li[FSA] content. Notably, these optimized conditions have resulted in an enhanced cycling performance in practical Li-S pouch cells. Our findings underscore the potential for improving the cycling performance of Li-S batteries, even when confronted with challenging constraints in electrolyte design.

The influence of unique interfacial networks based on egg white proteins for the stabilization of high internal phase Pickering emulsions: Physical stability and free fatty acid release kinetics.

This study was oriented towards the impacts of unique interfacial networks, formed by glycosylated and non-glycosylated egg white proteins, on the characteristics of high internal phase Pickering emulsions (HIPPEs). Glycosylated egg white protein particles (EWPG) manifested a more compact protein tertiary structure and amplified surface hydrophobicity, forming durable coral-like networks at the oil-water interface. The non-glycosylated egg white protein particles (EWP) could form spherical cluster interfacial networks. Raman spectroscopy analysis illuminated that EWPG could exhibit better interactions with aliphatic amino acids via hydrogen bonds and hydrophobic interactions. The release of free fatty acid (FFA) from both HIPPEs followed the first-order kinetic model with a combination of diffusion. EWPG-stabilized HIPPEs demonstrated superior physical stability and cellular antioxidant activity. This research shed light on the promising prospects of HIPPEs as promising amphiphilic delivery systems with capabilities to co-deliver hydrophilic and hydrophobic nutraceuticals and amplify their intracellular biological potency.

Casein-quaternary chitosan complexes induced the soft assembly of egg white peptide and curcumin for ulcerative colitis alleviation.

Soft assembly of peptide and curcumin (Cur) molecules enables functional integration by finding dynamic equilibrium states through non-covalent interactions. Herein, we developed two soft assembly systems, curcumin-egg white peptides (Cur-EWP) aggregations (AGs) and Cur-EWP-casein-quaternary chitosan (Cur-EWP-CA-QC) nanoparticles (NPs) to comparatively investigate their therapeutic effects on ulcerative colitis in mice and elucidate their underlying mechanism. Results revealed that Cur-EWP AGs, despite gastrointestinal tract instability, exhibited a propensity for swift accumulation within the colorectal region, enriching mucus-associated and short-chain fatty acid (SCAF)-producing bacteria, restoring the intestinal barrier damage. Whereas, Cur-EWP-CA-QC NPs, benefiting from their remarkable stability and exceptional mucosal adsorption properties, not only enhanced permeability of Cur and EWP in the small intestine to activate the immune response and boost tight junction protein expression but also, in their unabsorbed state, regulated the intestinal flora, exerting potent anti-inflammatory activity. Soft assembly of peptides and hydrophobic nutraceuticals could synergize biological activities to modulate chronic diseases.

Oral Synergism of Egg-White-Derived Peptides (EWDP) and Curcumin for Colitis Mitigation via Polysaccharide/Cyclodextrin Metal-Organic Framework-Based Assemblies.

Recently, oral deliverable strategies of multiple nutraceuticals for ulcerative colitis (UC) mitigation have attracted increasing attention. This study aimed to fabricate facile oral assemblies loaded with egg-white-derived peptides (EWDP) and curcumin based on carboxymethyl chitosan (CMCS) and an γ-cyclodextrin metal-organic framework (MOF). Herein, outer CMCS could coassemble with EWDP (both nutraceuticals and building blocks) into cobweb-like fibrils to promote bridging with inner MOF via coordinative noncovalent interactions (hydrogen bonding, hydrophobic interaction, and electrostatic interaction). Compared with conventional γ-cyclodextrin/MOF-based composites, the above coassembly could also endow the biocompatible assemblies with superior nanoscale colloidal properties, processing applicability (curcumin storage stability, bioaccessibility, and aqueous solubility), and bioactivity. Moreover, the oral synergism of EWDP and curcumin (initially nonsynergistic) for UC mitigation was achieved by alleviating inflammatory damage and gut microbiota imbalance. Overall, the novel assemblies could be a promising amplifier and platform to facilitate oral formulations of various nutraceuticals for food processing and UC relief.

Lithium Aluminate Nanoflakes as an Additive to Sulfur Cathodes for Enhanced Mass Transport in High-Energy-Density Lithium-Sulfur Pouch Cells Utilizing Sparingly Solvating Electrolytes.

The utilization of sparingly solvating electrolytes has been reckoned as a promising approach to realizing high-energy-density lithium-sulfur batteries under lean electrolyte conditions through decoupling the electrolyte amount from sulfur utilization. However, the inferior wettability of high-concentration sparingly solvating electrolytes compromises mass transport, thereby impeding the maximum utilization of active material in sulfur cathodes. To address this issue, in this study, we incorporate lithium aluminate (LiAlO2) nanoflakes as an additive to sulfur cathodes to enhance the mass transport by improving the percolation and accessibility of sparingly solvating electrolytes to the bulk of the electrodes. The electrochemical kinetics of LiAlO2-containing sulfur cathodes are investigated using the galvanostatic intermittent titration technique. The Li+ self-diffusion coefficients of electrode materials were estimated through pulsed-field gradient nuclear magnetic resonance (PFG-NMR) spectroscopy. Finally, a 193 Wh kg-1 Li-S pouch cell (excluding the mass of the laminated Al pouch) is demonstrated by utilizing the LiAlO2-incorporated sulfur cathode with a high S-loading of 4.3 mg cm-2 in a low electrolyte/sulfur (E/S) ratio of 3 µL mg-1. The Li-S pouch cell retains 80% of its initial specific cell capacity after 50 cycles. Our comprehensive understanding of the role of LiAlO2 additives in enhancing the mass transport and Li+ self-diffusion coefficient of sulfur cathodes will contribute immensely toward the development of high-energy-density Li-S batteries under lean electrolyte conditions.

Effects of Intestinal Microorganisms on Influenza-Infected Mice with Antibiotic-Induced Intestinal Dysbiosis, through the TLR7 Signaling Pathway.

BACKGROUND: Stability of intestinal flora is not only important for maintaining stable immune functions; it is also a key immune channel communicating the interaction between lung and intestine. In this study, probiotics and fecal microbiota transplantation (FMT) were used to regulate influenza-infected mice with antibiotic-induced intestinal dysbiosis and the effects of intestinal microorganisms on these mice were subsequently observed and evaluated. METHODS: Mice are housed in a normal environment with intranasal infection with influenza virus (FM1). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine messenger RNA expression and lung viral replication of toll-like receptor 7 (TLR7), myeloid differentiation primary reaction 88 (MyD88) and nuclear factor κB (ss) p65 in the TLR7 signaling pathway. Western blotting is used to measure the expression levels of TLR7, MyD88, and NF-κB p65 proteins. Flow cytometry was used to detect the proportion of Th17/T regulated cells. RESULTS: Results showed that compared with the simple virus group, both diversity and species of intestinal flora in influenza-infected mice with antibiotic-induced intestinal dysbiosis were lower, in vivo viral replication was significantly increased, lung and intestinal tissues were seriously damaged, degree of inflammation increased, expression of the TLR7 signaling pathway increased, and the Th1/Th2:Th17/Treg ratio decreased. Probiotics and FMT effectively regulated intestinal flora, improved pathological lung changes and inflammation caused by influenza infection, and adjusted the TLR7 signaling pathway and the Th1/Th2:Th17/Treg ratio. This effect was not obvious in TLR7-⁣/- mice.In summary, by affecting the TLR7 signaling pathway, intestinal microorganisms reduced the inflammatory response in the lungs of influenza-infected mice with imbalances in antibiotic flora. CONCLUSIONS: By affecting the TLR7 signaling pathway, intestinal microorganisms reduced the inflammatory response in the lungs of influenza-infected mice with imbalances in antibiotic flora. In summary, damage to lung tissue and intestinal mucosa in influenza-infected mice with antibiotic-induced intestinal dysbiosis is more serious compared to simple virus-infected mice. Improving intestinal flora using probiotics or FMT can alleviate intestinal inflammation and improve pulmonary inflammation through the TLR7 signaling pathway.

Identification and Verification of Potential Biomarkers in Renal Ischemia-Reperfusion Injury by Integrated Bioinformatic Analysis.

Background: Renal ischemia-reperfusion injury (RIRI) plays an important role in the poor prognosis of patients with renal transplants. However, the potential targets and mechanism of IRI are still unclear. Method: Differential gene expression (DEG) analysis and weighted correlation network analysis (WGCNA) were performed on the GSE27274 dataset. Pathway enrichment analysis on the DEGs was performed. To identify the hub DEGs, we constructed a protein-protein interaction (PPI) network. Finally, the hub genes were verified, and candidate drugs were screened from the DsigDB database. Results: A hundred DEGs and four hub genes (Atf3, Psmb6, Psmb8, and Psmb10) were screened out. Pathway enrichment analysis revealed that 100 DEGs were mainly enriched in apoptosis and the TNF signaling pathway. The four hub genes were verified in animal models and another dataset (GSE148420). Thereafter, a PPI network was used to identify the four hub genes (Atf3, Psmb6, Psmb8, and Psmb10). Finally, eight candidate drugs were identified as potential drugs. Conclusion: Three hub genes (Psmb6, Psmb8, and Psmb10) were associated with RIRI and could be potential novel biomarkers for RIRI.