Amorphous Oxyhalide Matters for Achieving Lithium Superionic Conduction.

The recently surged halide-based solid electrolytes (SEs) are great candidates for high-performance all-solid-state batteries (ASSBs), due to their decent ionic conductivity, wide electrochemical stability window, and good compatibility with high-voltage oxide cathodes. In contrast to the crystalline phases in halide SEs, amorphous components are rarely understood but play an important role in Li-ion conduction. Here, we reveal that the presence of amorphous component is common in halide-based SEs that are prepared via mechanochemical method. The fast Li-ion migration is found to be associated with the local chemistry of the amorphous proportion. Taking Zr-based halide SEs as an example, the amorphization process can be regulated by incorporating O, resulting in the formation of corner-sharing Zr-O/Cl polyhedrons. This structural configuration has been confirmed through X-ray absorption spectroscopy, pair distribution function analyses, and Reverse Monte Carlo modeling. The unique structure significantly reduces the energy barriers for Li-ion transport. As a result, an enhanced ionic conductivity of (1.35 ± 0.07) × 10-3 S cm-1 at 25 °C can be achieved for amorphous Li3ZrCl4O1.5. In addition to the improved ionic conductivity, amorphization of Zr-based halide SEs via incorporation of O leads to good mechanical deformability and promising electrochemical performance. These findings provide deep insights into the rational design of desirable halide SEs for high-performance ASSBs.

Identification of Optimal Parameters for Assessing Lymph Node Status of Patients with Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemoradiotherapy.

BACKGROUND: This study aimed to compare the prognostic discrimination power of pretreatment pathologic N stage (prepN), lymph node tumor regression grade (LNTRG), and posttreatment pathologic N (ypN) category for esophageal squamous cell carcinoma (ESCC) patients who received neoadjuvant chemoradiotherapy (nCRT) plus surgery. METHODS: The study reviewed 187 ESCC patients from two medical centers who underwent nCRT plus surgery. Pathologic LNTRG was defined by the proportion of viable tumor area within the tumor bed in lymph nodes (LNs). An average LNTRG then was calculated by averaging the tumor regression grade (TRG) score of all resected LNs. Lymph nodes containing regression changes or vital tumor cells were used for interpretation of the prepN stage, which reflects the estimated number of originally involved LNs. RESULTS: The ypN, prepN, and LNTRG categories had significant prognostic stratification power (p < 0.001, log-rank test). Multivariable cox regression showed that all three categories were independent prognostic factors of disease-free survival (DFS) (p < 0.05). The LNTRG category showed a better prognostic value for DFS prediction than the ypN and prepN categories (Akaike information criterion [AIC]: LNTRG [933.69], ypN [937.56], prepN [937.45]). Additionally, the superior predictive capacity of the LNTRG category was demonstrated by decision curve analysis. Similar results were discovered for patients with remaining diseased LNs. CONCLUSIONS: The three staging categories had prognostic relevance for DFS, with the LNTRG category seeming to have better prognostic indication power. Comprehensive consideration of the ypN status, prepN status, and LN regression may allow for better prognostic stratification of patients.

Pulse buildup dynamics in a self-starting Mamyshev oscillator.

The Mamyshev oscillator (MO) can generate high-performance pulses. However, due to their non-resonant cavities, they usually are not self-starting, and there is almost no effort to reveal the pulse buildup dynamics of the MO. This paper investigates the dynamic of single pulse (SP) and multi-pulse formation in a self-starting MO. It indicated that both SP self-starting and multi-pulse self-starting can be obtained by adjusting the oscillator parameters. More importantly, increasing pump power could only result in bound state pulses (BSPs) if SP self-starting was formed. With the increase of the pump power, the pulse number in BSPs would increase. However, multiple pulses could not be formed only by increasing the pump power, and the BSPs obtained here underwent SP generated from noise, amplified, and then bounded, which is different from conventional passive mode-locked fiber lasers (CPMLFLs). On the other hand, if multiple pulses were self-initiated, BSPs, pulse bunch, and harmonic mode-locked pulses (HMLPs) could be obtained by adjusting the polarization state and pump power in the cavity. Furthermore, once any of the above states are formed, if the oscillator polarization state and filter interval are unchanged, only increasing the pump power from zero, the original state can still be obtained, which is consistent with the characteristics of the CPMLFLs. These findings will provide new insights into the pulse dynamics of self-starting MO, which will be significant for studying ultrafast laser technology and nonlinear optics.

Template-Free Synthesis of Boron-Doped Graphitic Carbon Nitride Porous Nanotubes for Enhanced Photocatalytic Hydrogen Evolution.

The photocatalytic activity of g-C3N4 can be enhanced by improving photoinduced carrier separation and exposing sufficient reactive sites. In this study, we synthesized B-doped porous tubular g-C3N4 (BCNT) using a H3BO3-assisted supramolecular self-template method, wherein H3BO3 helped in B-doping, building a porous structure, and maintaining one-dimensional nanotubes. The tubular structure had an ultrathin tube wall and large aspect ratio, which are conducive to the directional transmission and separation of photogenerated carriers; moreover, the abundant pore structure of the tube wall could fully expose the reactive sites. The introduction of B and the cyano group modulated the bandgap of g-C3N4 and elevated the position of the conduction band, thus enhancing the photoreduction ability and effectively improving the hydrogen evolution performance. Consequently, the hydrogen evolution of BCNT-2 (220.8, 53.2 µmol·h-1) was 1.82 and 1.54 times that of ultrathin g-C3N4 nanosheets (CNN, 121.3, 34.6 µmol·h-1) under simulated sunlight and LED lamp irradiation, respectively. Thus, this work provides in-depth insights into the rational design of one-dimensional g-C3N4 nanotubes with high hydrogen evolution activity under visible irradiation.

Chemical composition analysis of Qingyan dropping pills using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

RATIONALE: This study developed a method for the rapid classification and identification of the chemical composition of Qingyan dropping pills (QDP) to provide the theoretical basis and data foundation for further in-depth research on the pharmacological substance basis of the formula and the selection of quality control indexes. METHODS: Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and data postprocessing technology were used to analyze the chemical composition of QDP. The fragmentation information on possible characteristic fragments and related neutral losses was summarized based on the literature and was compared with the MS data obtained from the assay, and thus a rapid classification and identification of chemical components in QDP could be achieved. RESULTS: A total of 73 compounds were identified, namely 24 flavonoids, 14 terpenoids, 30 organic acids and their esters, 3 alkaloids, and 2 phenylpropanoids. CONCLUSIONS: In this study, UHPLC-Q-TOF-MS and data postprocessing technology were used to realize the rapid classification and identification of the chemical constituents of QDP, which provided a comprehensive, efficient, and fast qualitative analysis method, a basis for further quality control and safe medication of QDP.

Epsin1-mediated exosomal sorting of Dll4 modulates the tubular-macrophage crosstalk in diabetic nephropathy.

Tubular epithelial cells (TECs) play critical roles in the development of diabetic nephropathy (DN), and can activate macrophages through the secretion of exosomes. However, the mechanism(s) of TEC-exosomes in macrophage activation under DN remains unknown. By mass spectrometry, 1,644 differentially expressed proteins, especially Dll4, were detected in the urine exosomes of DN patients compared with controls, which was confirmed by western blot assay. Elevated Epsin1 and Dll4/N1ICD expression was observed in kidney tissues in both DN patients and db/db mice and was positively associated with tubulointerstitial damage. Exosomes from high glucose (HG)-treated tubular cells (HK-2) with Epsin1 knockdown (KD) ameliorated macrophage activation, TNF-α, and IL-6 expression, and tubulointerstitial damage in C57BL/6 mice in vivo. In an in vitro study, enriched Dll4 was confirmed in HK-2 cells stimulated with HG, which was captured by THP-1 cells and promoted M1 macrophage activation. In addition, Epsin1 modulated the content of Dll4 in TEC-exosomes stimulated with HG. TEC-exosomes with Epsin1-KD significantly inhibited N1ICD activation and iNOS expression in THP-1 cells compared with incubation with HG alone. These findings suggested that Epsin1 could modulate tubular-macrophage crosstalk in DN by mediating exosomal sorting of Dll4 and Notch1 activation.

Rapid classification and identification of chemical components in three different Zanthoxylum species by ultra-high-performance-liquid chromatography quadrupole-orbitrap-mass spectrometry.

Zanthoxylum, as a medicinal and edible herbal medicine, has a long history and complex chemical composition. There are many varieties of Zanthoxylum, and there are differences in composition between varieties. In this study, a rapid classification and identification method for the main components of Zanthoxylum was established using ultra-high-performance-liquid chromatography quadrupole-orbitrap-mass spectrometry. The components of Shandong Zanthoxylum bungeanum, Wudu Zanthoxylum bungeanum, and Zanthoxylum schinifolium were identified by studying the characteristic fragmentations and neutral losses of characteristic components. A total of 48 common components and 24 different components were identified and the fragmentation patterns of the main components, such as flavonoids, alkaloids, and organic acids were summarized. These findings provided a reference for the study of pharmacodynamic substance basis and quality control of different varieties of Zanthoxylum.

Establishment of the Diagnostic Signature of Ferroptosis Genes in Multiple Sclerosis.

Ferroptosis is a novel form of membrane-dependent cell death that differs from other cell death modalities such as necrosis, apoptosis, and autophagy. Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system primarily affecting brain and spinal cord neurons. Although the pathogenesis of these two conditions may seem unrelated, recent studies have indicated a connection between ferroptosis and multiple sclerosis. In fact, ferroptosis plays a significant role in the development of MS, as evidenced by the presence of elevated iron levels and iron metabolism abnormalities in the brains, spinal cords, and other neurons of MS patients. These abnormalities disrupt iron homeostasis within cells, leading to the occurrence of ferroptosis. However, there is currently a lack of research on the diagnostic value of ferroptosis-related genes in multiple sclerosis. In this study, we employed bioinformatics methods to identify ferroptosis-related genes (ATM, GSK3B, HMGCR, KLF2, MAPK1, NFE2L1, NRAS, PCBP1, PIK3CA, RPL8, VDAC3) associated with the diagnosis of multiple sclerosis and constructed a diagnostic model. The results demonstrated that the diagnostic model accurately identified the patients' condition. Subsequently, subgroup analysis was performed based on the expression levels of ferroptosis-related genes, dividing patients into high and low expression groups. The results showed differences in immune function and immune cell infiltration between the two groups. Our study not only confirms the correlation between ferroptosis and multiple sclerosis but also demonstrates the diagnostic value of ferroptosis-related genes in the disease. This provides guidance for clinical practice and direction for further mechanistic research.

Reassembly of Peptide Nanofibrils on Live Cell Surfaces Promotes Cell-Cell Interactions.

Nature regulates cellular interactions through the cell-surface molecules and plasma membranes. Despite advances in cell-surface engineering with diverse ligands and reactive groups, modulating cell-cell interactions through scaffolds of the cell-binding cues remains a challenging endeavor. Here, we assembled peptide nanofibrils on live cell surfaces to present the ligands that bind to the target cells. Surprisingly, with the same ligands, reducing the thermal stability of the nanofibrils promoted cellular interactions. Characterizations of the system revealed a thermally induced fibril disassembly and reassembly pathway that facilitated the complexation of the fibrils with the cells. Using the nanofibrils of varied stabilities, the cell-cell interaction was promoted to different extents with free-to-bound cell conversion ratios achieved at low (31%), medium (54%), and high (93%) levels. This study expands the toolbox to generate desired cell behaviors for applications in many areas and highlights the merits of thermally less stable nanoassemblies in designing functional materials.

Arginine Regulates Skeletal Muscle Fiber Type Formation via mTOR Signaling Pathway.

The composition of skeletal muscle fiber types affects the quality of livestock meat and human athletic performance and health. L-arginine (Arg), a semi-essential amino acid, has been observed to promote the formation of slow-twitch muscle fibers in animal models. However, the precise molecular mechanisms are still unclear. This study investigates the role of Arg in skeletal muscle fiber composition and mitochondrial function through the mTOR signaling pathway. In vivo, 4-week C56BL/6J male mice were divided into three treatment groups and fed a basal diet supplemented with different concentrations of Arg in their drinking water. The trial lasted 7 weeks. The results show that Arg supplementation significantly improved endurance exercise performance, along with increased SDH enzyme activity and upregulated expression of the MyHC I, MyHC IIA, PGC-1α, and NRF1 genes in the gastrocnemius (GAS) and quadriceps (QUA) muscles compared to the control group. In addition, Arg activated the mTOR signaling pathway in the skeletal muscle of mice. In vitro experiments using cultured C2C12 myotubes demonstrated that Arg elevated the expression of slow-fiber genes (MyHC I and Tnnt1) as well as mitochondrial genes (PGC-1α, TFAM, MEF2C, and NRF1), whereas the effects of Arg were inhibited by the mTOR inhibitor rapamycin. In conclusion, these findings suggest that Arg modulates skeletal muscle fiber type towards slow-twitch fibers and enhances mitochondrial functions by upregulating gene expression through the mTOR signaling pathway.

Regulating pathway for bacterial diversities toward improved ecological benefits of thiencarbazone-methyl·isoxaflutole application: A field experiment.

Herbicide abuse has a significantly negative impact on soil microflora and further influences the ecological benefit. The regulating measures and corresponding mechanisms mitigating the decreased bacterial diversity due to herbicide use have rarely been studied. A field experiment containing the application gradient of an efficient maize herbicide thiencarbazone-methyl·isoxaflutole was performed. The relationship between soil bacterial community and thiencarbazone-methyl·isoxaflutole use was revealed. Modified attapulgite was added to explore its impacts on soil microflora under the thiencarbazone-methyl·isoxaflutole application. Based on the analytic network process-entropy weighting method-TOPSIS method model, the ecological benefit focusing on microbial responses was quantitatively estimated along with technical effectiveness and economic benefit. The results showed that the diversity indices of soil microflora, especially the Inv_Simpson index, were reduced at the recommended, 5 and 10 times the recommended dosages of thiencarbazone-methyl·isoxaflutole use. The Flavisolibacter bacteria was negatively correlated with the residues in soils based on the random forest model and correlation analysis, indicating a potential degrader of thiencarbazone-methyl·isoxaflutole residues. The structural equation model further confirmed that the high soil water content and soil pH promoted the function of Flavisolibacter bacteria, facilitated the dissipation of thiencarbazone-methyl·isoxaflutole residues and further improved the diversity of soil microflora. In addition, the presence of modified attapulgite was found to increase the soil pH, which may improve bacterial diversity through the regulating pathway. This explained the high ecological benefits of the treatment where the thiencarbazone-methyl·isoxaflutole was applied at the recommended dosage rates in conjunction with modified attapulgite addition. Therefore, the comprehensive benefits of thiencarbazone-methyl·isoxaflutole application with a focus on ecological benefits can be improved by regulating the soil pH with modified attapulgite.

A Dual Anion Chemistry-Based Superionic Glass Enabling Long-Cycling All-Solid-State Sodium-Ion Batteries.

Glassy Na-ion solid-state electrolytes (GNSSEs) are an important group of amorphous SSEs. However, the insufficient ionic conductivity of state-of-the-art GNSSEs at room temperature lessens their promise in the development of all-solid-state Na-ion batteries (ASSNIBs) with high energy density and improved safety. Here we report the discovery of a new sodium superionic glass, 0.5Na2 O2 -TaCl5 (NTOC), based on dual-anion sublattice of oxychlorides. The unique local structures with abundant bridging and non-bridging oxygen atoms contributes to a highly disordered Na-ion distribution as well as low Na+ migration barrier within NTOC, enabling an ultrahigh ionic conductivity of 4.62 mS cm-1 at 25 °C (more than 20 times higher than those of previously reported GNSSEs). Moreover, the excellent formability of glassy NTOC electrolyte and its high electrochemical oxidative stability ensure a favourable electrolyte-electrode interface, contributing to superior cycling stability of ASSNIBs for over 500 cycles at room temperature. The discovery of glassy NTOC electrolyte would reignite research enthusiasm in superionic glassy SSEs based on multi-anion chemistry.

Cubic Iodide Lix YI3+x Superionic Conductors through Defect Manipulation for All-Solid-State Li Batteries.

Halide solid electrolytes (SEs) have attracted significant attention due to their competitive ionic conductivity and good electrochemical stability. Among typical halide SEs (chlorides, bromides, and iodides), substantial efforts have been dedicated to chlorides or bromides, with iodide SEs receiving less attention. Nevertheless, compared with chlorides or bromides, iodides have both a softer Li sublattice and lower reduction limit, which enable iodides to possess potentially high ionic conductivity and intrinsic anti-reduction stability, respectively. Herein, we report a new series of iodide SEs: Lix YI3+x (x=2, 3, 4, or 9). Through synchrotron X-ray/neutron diffraction characterizations and theoretical calculations, we revealed that the Lix YI3+x SEs belong to the high-symmetry cubic structure, and can accommodate abundant vacancies. By manipulating the defects in the iodide structure, balanced Li-ion concentration and generated vacancies enables an optimized ionic conductivity of 1.04 × 10-3  S cm-1 at 25 °C for Li4 YI7 . Additionally, the promising Li-metal compatibility of Li4 YI7 is demonstrated via electrochemical characterizations (particularly all-solid-state Li-S batteries) combined with interface molecular dynamics simulations. Our study on iodide SEs provides deep insights into the relation between high-symmetry halide structures and ionic conduction, which can inspire future efforts to revitalize halide SEs.

The type III polyketide synthase supergene family in plants: complex evolutionary history and functional divergence.

Type III polyketide synthases (PKSs) are key enzymes involved in the biosynthesis of a variety of plant specialized metabolites, including flavonoids, stilbenes, and sporopollenin, to name a few. These enzymes likely played vital roles in plant adaptation during their transition from aquatic to terrestrial habitats and their colonization of specific ecological environments. Members of this supergene family have diverse functions, but how type III PKSs and their functions have evolved remains poorly understood. Here, we conducted comprehensive phylogenomics analysis of the type III PKS supergene family in 60 species representing the major plant lineages and elucidated the classification, origin, and evolutionary history of each class. Molecular evolutionary analysis of the typical chalcone synthase and stilbene synthase types revealed evidence for strong positive natural selection in both the Pinaceae and Fabaceae lineages. The positively selected sites of these proteins include residues at the catalytic tunnel entrance and homodimer interface, which might have driven the functional divergence between the two types. Our results also suggest that convergent evolution of enzymes involved in plant flavonoid biosynthesis is quite common. The results of this study provide new insights into the origin, evolution, and functional diversity of plant type III PKSs. In addition, they serve as a guide for the enzymatic engineering of plant polyketides.

Superionic Conducting Halide Frameworks Enabled by Interface-Bonded Halides.

The revival of ternary halides Li-M-X (M = Y, In, Zr, etc.; X = F, Cl, Br) as solid-state electrolytes (SSEs) shows promise in realizing practical solid-state batteries due to their direct compatibility toward high-voltage cathodes and favorable room-temperature ionic conductivities. Most of the reported superionic halide SSEs have a structural pattern of [MCl6]x- octahedra and generate a tetrahedron-assisted Li+ ion diffusion pathway. Here, we report a new class of zeolite-like halide frameworks, SmCl3, for example, in which 1-dimensional channels are enclosed by [SmCl9]6- tricapped trigonal prisms to provide a short jumping distance of 2.08 Å between two octahedra for Li+ ion hopping. The fast Li+ diffusion along the channels is verified through ab initio molecular dynamics simulations. Similar to zeolites, the SmCl3 framework can be grafted with halide species to obtain mobile ions without altering the base structure, achieving an ionic conductivity over 10-4 S cm-1 at 30 °C with LiCl as the adsorbent. Moreover, the universality of the interface-bonding behavior and ionic diffusion in a class of framework materials is demonstrated. It is suggested that the ionic conductivity of the MCl3/halide composite (M = La-Gd) is likely in correlation with the ionic conductivity of the grafted halide species, interfacial bonding, and framework composition/dimensions. This work reveals a potential class of halide structures for superionic conductors and opens up a new frontier for constructing zeolite-like frameworks in halide-based materials, which will promote the innovation of superionic conductor design and contribute to a broader selection of halide SSEs.

ATF5 regulates tubulointerstitial injury in diabetic kidney disease via mitochondrial unfolded protein response.

BACKGROUND: Mitochondrial quality control (MQC) plays a critical role in the progression of tubulointerstitial injury in diabetic kidney disease (DKD). The mitochondrial unfolded protein response (UPRmt), which is an important MQC process, is activated to maintain mitochondrial protein homeostasis in response to mitochondrial stress. Activating transcription factor 5 (ATF5) is critical in the mammalian UPRmt via mitochondria-nuclear translocation. However, the role of ATF5 and UPRmt in tubular injury under DKD conditions is unknown. METHODS: ATF5 and UPRmt-related proteins including heat shock protein 60 (HSP60) and Lon peptidase 1 (LONP1), in DKD patients and db/db mice were examined by immunohistochemistry (IHC) and western blot analysis. Eight-week-old db/db mice were injected with ATF5-shRNA lentiviruses via the tail vein, and a negative lentivirus was used as a control. The mice were euthanized at 12 weeks, and dihydroethidium (DHE) and TdT-mediated dUTP nick end labeling (TUNEL) assays were performed to evaluate reactive oxygen species (ROS) production and apoptosis in kidney sections, respectively. In vitro, ATF5-siRNA, ATF5 overexpression plasmids or HSP60-siRNA were transfected into HK-2 cells to evaluate the effect of ATF5 and HSP60 on tubular injury under ambient hyperglycemic conditions. Mitochondrial superoxide (MitoSOX) staining was used to gauge mitochondrial oxidative stress levels, and the early stage of cell apoptosis was examined by Annexin V-FITC kits. RESULTS: Increased ATF5, HSP60 and LONP1 expression was observed in the kidney tissue of DKD patients and db/db mice and was tightly correlated with tubular damage. The inhibition of HSP60 and LONP1, improvements in serum creatinine, tubulointerstitial fibrosis and apoptosis were observed in db/db mice treated with lentiviruses carrying ATF5 shRNA. In vitro, the expression of ATF5 was increased in HK-2 cells exposed to high glucose (HG) in a time-dependent manner, which was accompanied by the overexpression of HSP60, fibronectin (FN) and cleaved-caspase3 (C-CAS3). ATF5-siRNA transfection inhibited the expression of HSP60 and LONP1, which was accompanied by reduced oxidative stress and apoptosis in HK-2 cells exposed to sustained exogenous high glucose. ATF5 overexpression exacerbated these impairments. HSP60-siRNA transfection blocked the effect of ATF5 on HK-2 cells exposed to continuous HG treatment. Interestingly, ATF5 inhibition exacerbated mitochondrial ROS levels and apoptosis in HK-2 cells in the early period of HG intervention (6 h). CONCLUSIONS: ATF5 could exert a protective effect in a very early stage but promoted tubulointerstitial injury by regulating HSP60 and the UPRmt pathway under DKD conditions, providing a potential target for the prevention of DKD progression.

A Collection of RPA-Based Photoelectrochemical Assays for the Portable Detection of Multiple Pathogens.

Portable, ultrasensitive, and simultaneously quantitative detection of the nucleic acids of multiple foodborne pathogens is critical to public health. However, the current testing methods depend on costly equipment and tedious amplification steps. In this study, we propose a photoelectrochemical (PEC) biosensor combined with recombinase polymerase amplification (RPA) technology (RPA-PEC) for the rapid detection of multiple foodborne pathogens under irradiation of 980 nm light. In particular, two working surfaces were designed on homemade three-dimensional screen-printed paper-based electrodes. The genomic DNAs of Escherichia coli O157:H7 and Staphylococcus aureus was initiated by RPA on the corresponding electrode surfaces, thus forming a lab-on-paper platform. Using the formed DNA-PEC signaler, photocurrents were achieved at 37 °C after only 20 min of RPA. The detection performance was superior to that of conventional agarose gel electrophoresis, with detection limits of 3.0 and 7.0 copies/µL for E. coli O157:H7 and S. aureus, respectively. Our study pioneers a new RPA-PEC method for foodborne pathogens and provides directions for the construction of lab-on-paper platforms for the portable detection of multiple nucleic acids.

Identification of transcription factors related to diabetic tubulointerstitial injury.

BACKGROUND: Diabetic nephropathy (DN) is a main cause of chronic renal failure. Despite decades of extensive study, the molecular mechanisms underlying diabetic tubulointerstitial injury remain unclear. We aim to identify key transcription factor genes involved in diabetic tubulointerstitial injury. METHODS: A microarray dataset (GSE30122) from Gene Expression Omnibus (GEO) was downloaded. A total of 38 transcription factor genes based on 166 differentially expressed genes (DEGs) were identified by UCSC_TFBS. RESULTS: The regulatory network showed connections between the top 10 transcription factors and their target DEGs. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of targeted DEGs indicated that extracellular space, extracellular exosome, cell surface and complement and coagulation cascades were most significantly enriched. Utilizing Nephroseq v5 online platform, the mRNA expression pattern analysis of transcription factor genes demonstrated that mRNA expression of CDC5, CEBPA, FAC1, HFH1, IRF1, NFE2 and TGIF1 increased in renal tubulointerstitium of DN patients compared with normal controls while that of CEBPB and FOXO4 decreased in renal tubulointerstitium of DN patients compared with normal controls. Correlation analysis between mRNA expression of transcription factor genes in renal tubulointerstitium and clinical features showed that AP1, BACH1, CDC5, FAC1, FOXD1, FOXJ2, FOXO1, FOXO4, HFH1, IRF1, POU3F2, SOX5, SOX9, RSRFC4, S8 and TGIF1 may be related to diabetic tubulointerstitial injury. CONCLUSIONS: (1) CDC5, FAC1, FOXO4, HFH1, IRF1 and TGIF1 may be key transcription factor genes. (2)Transcription factors involved in diabetic tubulointerstitial injury may become prospective targets for diagnosis and treatment of DN.

Asp-containing actinomycin and tetracyclic chromophoric analogues from the Streptomyces sp. strain S22.

Three novel actinomycins, actimomycin S (1), neo-actinomycins C and D (2 and 3), and one new benzo[d]oxazole alkaloid (4) were isolated from the Streptomyces sp. strain S22, along with three known congeners F9 (5), X2 (6) and X0ß (7) and 2-acetylamino-3-hydroxyl-4-methyl-benzoic acid methyl ester (8). The structures of the new products were elucidated by spectroscopic methods, and the absolute configuration of amino acid residues was determined by Marfey's analysis. Actinomycin S contains an aspartic acid (Asp) residue in the ß-peptidolactone ring. This is the first report of an Asp residue within an actinomycin-type natural product. Notably, neo-actinomycins C and D feature a rare tetracyclic 5H-oxazolo[4,5-b]phenoxazine chromophore. Among these, neo-actinomycin D, with an unprecedented molecular formula, represents the highest molecular weight member in the actinomycin family. Actinomycins 1-3 exhibited antimicrobial activity against multiple resistant "ESKAPE" pathogens with MIC values ranging from 1.25 to 80.0 µg mL-1. In addition, 1-3 showed potent cytotoxic activities against the HepG2 liver carcinoma cell line with IC50 values of 0.10, 0.32, and 0.024 µM, respectively. Furthermore, 1 inhibited cell proliferation by inducing G0-G1 phase arrest in the cell cycle.

Rapid identification of chemical compositions of three species of Schisandra chinensis by ultra-high-performance liquid chromatography quadrupole-orbitrap-mass spectrometry.

Schisandra chinensis is a traditional Chinese medicine, which has played an important role in the field of medicine and food. In this study, ultra-high-performance liquid chromatography quadrupole-orbitrap-mass spectrometry was used to rapidly classify and identify the chemical compositions. Note that 32, 28, and 30 kinds of compounds were successfully identified from northern Schisandra chinensis, vinegar-processed Schisandra chinensis, and wine-processed Schisandra chinensis, respectively. The cleavage patterns of various components including lignans, organic acids, flavonoids, and terpenoids were summarized, and the effects of different processing methods on Schisandra chinensis were analyzed through chemical composition. This method realized the rapid classification and identification of raw Schisandra chinensis and two different processed products, and provided references for improving the traditional processing methods, strengthening quality control, and ensuring safe clinical application.