Analysis of different expression RNA binding protein genes in mouse microglia cell from the brains of mice 72 h after subarachnoid hemorrhage or sham operation.

BACKGROUND: The prognosis of brain injury caused by subarachnoid hemorrhage (SAH) is poor. Previous studies showed that abnormal function of RBPs might be involved in brain injury, neuroinflammation and further affect microglia homeostasis. However, no studies have systematically analyzed the genome-wide abnormal expression of RBPs genes in microglia during SAH. METHODS: RNA-seq data of microglia from the SAH mouse group (SAH) and control sham-operated mouse group (sham) were downloaded from the GEO database in GSE167957, including four samples from the sham group and four samples from the SAH group for subsequent analysis.Utilizing GO and KEGG functional enrichment analyses, we conducted a comprehensive study of differentially expressed genes (DEGs), alternative splicing patterns, and co-expression networks to gain deeper insights into the differential expression of RNA-binding proteins (RBPs) and differential alternative splicing events (ASEs) between the SAH (subarachnoid hemorrhage) and sham groups. This analysis aimed to elucidate the potential mechanisms underlying the aberrant expression of RBPs in microglia during brain injury caused by SAH. RESULTS: ASEs and co-expression analyses of differentially expressed RBPs and differential ASEs were carried out in microglia in terms of gene expression. GO and KEGG functional enrichment analysis showed that aberrantly expressed RBPs such as Mcm7, Mtdh, SRSF3, and Hnrnpa2b1 may affect and regulate downstream Csnk1d, Uckl1 and other protein phosphorylation-related genes by alterative splicing. CONCLUSION: RBPs were aberrantly expressed in microglia during the development of brain injury secondary to SAH, regulating alterative splicing of downstream genes and influencing the progression of SAH brain injury in this study. This implies that RBPs are important for the identification of new therapeutic targets for brain injury after SAH.

Structural basis for linker histone H5-nucleosome binding and chromatin fiber compaction.

The hierarchical packaging of chromatin fibers plays a critical role in gene regulation. The 30-nm chromatin fibers, a central-level structure bridging nucleosomal arrays to higher-order organizations, function as the first level of transcriptional dormant chromatin. The dynamics of 30-nm chromatin fiber play a crucial role in biological processes related to DNA. Here, we report a 3.6-angstrom resolution cryogenic electron microscopy structure of H5-bound dodecanucleosome, i.e., the chromatin fiber reconstituted in the presence of linker histone H5, which shows a two-start left-handed double helical structure twisted by tetranucleosomal units. An atomic structural model of the H5-bound chromatin fiber, including an intact chromatosome, is built, which provides structural details of the full-length linker histone H5, including its N-terminal domain and an HMG-motif-like C-terminal domain. The chromatosome structure shows that H5 binds the nucleosome off-dyad through a three-contact mode in the chromatin fiber. More importantly, the H5-chromatin structure provides a fine molecular basis for the intra-tetranucleosomal and inter-tetranucleosomal interactions. In addition, we systematically validated the physiological functions and structural characteristics of the tetranucleosomal unit through a series of genetic and genomic studies in Saccharomyces cerevisiae and in vitro biophysical experiments. Furthermore, our structure reveals that multiple structural asymmetries of histone tails confer a polarity to the chromatin fiber. These findings provide structural and mechanistic insights into how a nucleosomal array folds into a higher-order chromatin fiber with a polarity in vitro and in vivo.

GHSR deficiency exacerbates Parkinson's disease pathology by impairing autophagy.

In Parkinson's disease (PD), exogenous ghrelin protects dopaminergic neurons through its receptor, growth hormone secretagogue receptor (GHSR). However, in contrast to the strikingly low levels of ghrelin, GHSR is highly expressed in the substantia nigra (SN). What role does GHSR play in dopaminergic neurons is unknown. In this study, using GHSR knockout mice (Ghsr-/- mice) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model, we found that GHSR deletion aggravated dopaminergic neurons degeneration, and the expression and activity of GHSR were significantly reduced in PD. Furthermore, we explored the potential mechanism that GHSR deficiency aggregated PD-related neurodegeneration. We showed that DEPTOR, a subunit of mTORC1, was overexpressed in Ghsr-/- mice, positively regulating autophagy and enhancing autophagy initiation. The expression of lysosomal markers was abnormal, implying lysosomal dysfunction. As a result, the damaged mitochondria could not be effectively eliminated, which ultimately exacerbated the injury of nigral dopaminergic neurons. In particular, we demonstrated that DEPTOR could be transcriptionally regulated by KLF4. Specific knockdown of KLF4 in dopaminergic neurons effectively alleviated neurodegeneration in Ghsr-/- mice. In summary, our results suggested that endogenous GHSR deletion-compromised autophagy by impairing lysosomal function, is a key contributor to PD, which provided ideas for therapeutic approaches involving the manipulation of GHSR.

MiR-125b-1-3p-mediated UQCRB inhibition facilitates mitochondrial metabolism disorders in a rat cellular senescencemodel.

BACKGROUD: Cellular senescence is closely related to human aging and multiple aging-related diseases, and impaired mitochondrial energy metabolism is an important mechanism of cellular senescence. Notably, microRNA-125b-1-3p (miR-125b-1-3p) is a microRNA (miR, miRNA) that may be associated with mitochondrial energy metabolism. Ubiquinol-cytochrome c reductase binding protein (UQCRB) gene, predicted by bioinformatics tools to be targeted by miR-125b-1-3p, could serve as a novel diagnostic indicator and therapeutic target for cellular senescence-associated diseases, as well as a new idea for delaying aging. METHODS: First, the dual-luciferase reporter gene assay was used to identify UQCRB as a target gene of miR-125b-1-3p. Next, miRNA interference technology was conducted to verify that miR-125b-1-3p could negatively regulate the expression of UQCRB. Subsequently, the influence of miR-125b-1-3p on mitochondrial energy metabolism function was explored by observing the internal substances and ultrastructure of mitochondria. Further, an in vitro model of cellular senescence was established in rat renal tubular epithelial cells, which was characterized by detecting senescence-related proteins p16 and p21 and beta-galactosidase (ß-gal) activity. Finally, the mitochondrial energy metabolism function of hydrogen peroxide (H2O2)-incubated cells was explored. RESULTS: The experimental results revealed that miR-125b-1-3p affected the mitochondrial energy metabolism function by inhibiting the target gene UQCRB. Meanwhile, the level of mitochondrial energy metabolism function in H2O2-incubated senescent cells was lower than that in normal cells. CONCLUSION: In this study, we identified the target gene, UQCRB, of miR-125b-1-3p, and demonstrated its role in the pathway of mitochondrial energy metabolism, as well as its possible effect on cellular senescence through this pathway. The ameliorative effects on cellular senescence can be further explored in subsequent studies to provide additional options for delaying aging or treating aging-related diseases.

Determination of doxorubicin in plasma and tissues of mice by UPLC-MS/MS and its application to pharmacokinetic study.

A rapid and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous determination of doxorubicin (DOX) in mouse plasma and tissues, including the heart, liver, spleen, lung, kidney and tumor, and to investigate the pharmacokinetics and distribution in mice. In this study, daunorubicin (DNR) was used as an internal standard, and the mobile phase consisted of ammonium formate 2 mM containing 0.1 % formic acid (A) and acetonitrile (B), the chromatographic column was ACQUITY UPLC BEHTM C18 with a gradient elution at a flow rate of 0.2 mL/min. Electrospray ionization (ESI) in positive ion pattern was utilized for the ion separation of DOX, with the ions used for quantitative analysis being DOX m/z 544.28 â†’ 397.10 and DNR m/z 528.35 â†’ 321.08, respectively. The results showed that a good linear relationship in the calibration curve range of 1-800 ng/mL in mouse plasma and 1-2500 ng/g in tissues (R2 > 0.99) with the limits of quantification of 1 ng/mL in plasma and tissues. The method exhibited good matrix effect and extraction recovery, with the intra-day and inter-day precision of plasma and tissue were less than 10.3 % and 15.4 %, and the relative error (RE) were both less than ±14.8 % and ±18.9 %, respectively. The stability results under different conditions were found to be accurate. It also revealed the distribution of DOX in various tissues of mice, with the concentration ranking as liver > heart > kidney > spleen > lung > tumor. This method was successfully used to the study for the pharmacokinetics in plasma and drug distribution in tissues of BALB/c mice.

Fluid-Induced Piezoelectric Field Enhancing Photo-Assisted Zn-Air Batteries Based on a Fe@P(V-T) Microhelical Cathode.

Photo-assisted Zn-air batteries can accelerate the kinetics of oxygen reduction and oxygen evolution reactions (ORR/OER); however, challenges such as rapid charge carrier recombination and continuous electrolyte evaporation remain. Herein, for the first time, piezoelectric catalysis is introduced in a photo-assisted Zn-air battery to improve carrier separation capability and accelerate the ORR/OER kinetics of the photoelectric cathode. The designed microhelical catalyst exploits simple harmonic vibrations to regenerate the built-in electric field continuously. Specifically, in the presence of the low-frequency kinetic energy that occurs during water flow, the piezoelectric-photocoupling catalyst of poly(vinylidene fluoride-co-trifluoroethylene)@ferric oxide(Fe@P(V-T)) is periodically deformed, generating a constant reconfiguration of the built-in electric field that separates photogenerated electrons and holes continuously. Further, on exposure to microvibrations, the gap between the charge and discharge potentials of the Fe@P(V-T)-based photo-assisted Zn-air battery is reduced by 1.7 times compared to that without piezoelectric assistance, indicating that piezoelectric catalysis is highly effective for enhancing photocatalytic efficiency. This study provides a thorough understanding of coupling piezoelectric polarization and photo-assisted strategy in the field of energy storage and opens a fresh perspective for the investigation of multi-field coupling-assisted Zn-air batteries.

FACT mediates the depletion of macroH2A1.2 to expedite gene transcription.

The histone variant macroH2A is generally linked to transcriptionally inactive chromatin, but how macroH2A regulates chromatin structure and functions in the transcriptional process remains elusive. This study reveals that while the integration of human macroH2A1.2 into nucleosomes does not affect their stability or folding dynamics, it notably hinders the maintenance of facilitates chromatin transcription's (FACT's) function. We show that FACT effectively diminishes the stability of macroH2A1.2-nucleosomes and expedites their depletion subsequent to the initial unfolding process. Furthermore, we identify the residue S139 in macroH2A1.2 as a critical switch to modulate FACT's function in nucleosome maintenance. Genome-wide analyses demonstrate that FACT-mediated depletion of macroH2A-nucleosomes allows the correct localization of macroH2A, while the S139 mutation reshapes macroH2A distribution and influences stimulation-induced transcription and cellular response in macrophages. Our findings provide mechanistic insights into the intricate interplay between macroH2A and FACT at the nucleosome level and elucidate their collective role in transcriptional regulation and immune response of macrophages.

Enhancing Photoreduction of Cr(VI) through a Multivalent Manganese(II)-Organic Framework Incorporating Anthracene Moieties.

Exploiting a photocatalyst with high stability and excellent activity for Cr(VI) reduction under mild conditions is crucial yet challenging. Herein, the rigid aromatic multicarboxylate ligand with chromophore anthracene was selected to coordinate with multivalent metal ion manganese and to obtain a stable two-dimensional (2D) Mn-based metal-organic framework (MOF), LCUH-120, which can efficiently and quickly convert Cr(VI) into Cr(III) under light without the need for any additional photosensitizer. The efficient photosensitive anthracene group serves as a photosensitizer center and multivalent Mn(II) ion as a photocatalyst center in LCUH-120, and the conversion of Cr(VI) to Cr(III) can be realized completely in just 40 min. Specifically, the rate constant (k) and reduction rate of the Cr(VI) photocatalytic reaction can be high up to 0.134 min-1 and 2.50 mgCr(VI) g-1cata min-1 in an acidic environment (pH = 2), respectively. Compared to our previously reported three-dimensional (3D) Sm-MOF, LCUH-120 exhibits a significantly higher catalytic reaction rate, which might be ascribed to the fact that the photocatalyst center Mn node can improve the rate of electron transfer and promote the separation of holes and photogenerated electrons. In an acidic environment, the reaction mechanism can be verified through various contrast experiments and theoretical simulations.

Low concentrations of methyl jasmonate promote plant growth and mitigate Cd toxicity in Cosmos bipinnatus.

Cadmium (Cd) is a biologically non-essential heavy metal, a major soil pollutant, and extremely harmful to plants. The phytohormone methyl jasmonate (MeJA) plays an important role in plant heavy-metal resistance. However, the understanding of the effects of MeJA supply level on alleviating Cd toxicity in plants is limited. Here, we investigated how MeJA regulated the development of physiological processes and cell wall modification in Cosmos bipinnatus. We found that low concentrations of MeJA increased the dry weight of seedlings under 120 µM Cd stress by reducing the transport of Cd from roots to shoots. Moreover, a threshold concentration of exogenous MeJA increased the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in plant roots, the concentration of Cd in the root cell wall, and the contents of pectin and hemicellulose 1 polysaccharides, through converting Cd into pectin-bound forms. These results suggested that MeJA mitigated Cd toxicity by modulating root cell wall polysaccharide and functional group composition, especially through pectin polysaccharides binding to Cd, with effects on Cd transport capacity, specific chemical forms of Cd, and homeostatic antioxidant systems in C. bipinnatus.

Integrating serum pharmacochemistry, network pharmacology and untargeted metabolomics strategies to reveal the material basis and mechanism of action of Feining keli in the treatment of chronic bronchitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Feining keli (FNKL) is herbal preparation mainly made from Senecio cannabifolius Less., In recent years, more and more studies have found that FNKL has excellent therapeutic effects on chronic bronchitis (CB). Nevertheless, its pharmacodynamic material basis and mechanism of action are still unknown. AIM OF THE STUDY: This study aimed to explore the pharmacodynamic material basis and mechanism of action of FNKL in treating CB. MATERIALS AND METHODS: The CB rat model was induced using nasal drops of lipopolysaccharide (LPS) in combination with smoking. Various assessments including behavioral and body mass examination, lung index measurement, enzyme linked immunosorbent assay (ELISA), as well as histological analyses using hematoxylin and eosin (H&E) and Masson staining were conducted to validate the reliability of the CB model. The serum components of FNKL in CB rats were identified using ultra-high-performance liquid chromatography Orbitrap Exploris mass spectrometer (UHPLC-OE-MS). Network pharmacology was used to predict the network of action of the active ingredients in FNKL based on these serum components. Signaling pathways were enriched and analyzed, and molecular docking was conducted for key targets. Molecular dynamics simulations were performed using GROMACS software. The mechanism was confirmed through a series of experiments including Western blot (WB), immunofluorescence (IF), and reverse transcription (RT)-PCR. Additionally, untargeted metabolomics was employed to identify biomarkers and relevant metabolic pathways associated with the treatment of CB with FNKL. RESULTS: In CB rats, FNKL improved body mass, lung index, and pathological damage of lung tissues. It also decreased interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), malonaldehyde (MDA) levels, and percentage of lung collagen fiber area. Furthermore, FNKL increased IL-10 and superoxide dismutase (SOD) levels, which helped alleviate bronchial inflammation in the lungs. A total of 70 FNKL chemical components were identified in CB rat serum. Through network pharmacology analysis, 5 targets, such as PI3K, AKT, NF-κB, HIF-1α, and MYD88, were identified as key targets of FNKL in the treatment of CB. Additionally, the key signaling pathways identified were PI3K/AKT pathway、NF-κB/MyD88 pathway、HIF-1α pathway. WB, IF, and RT-PCR experiments were conducted to confirm the findings. Molecular docking studies demonstrated successful docking of 16 potential active components with 5 key targets. Additionally, molecular dynamics simulations indicated the stability of quercetin-3-galactoside and HIF-1α. Metabolomics analysis revealed that FNKL primarily regulated pathways related to alpha-linolenic acid metabolism, primary bile acid biosynthesis, bile secretion, arachidonic acid metabolism, neuroactive ligand-receptor interaction, and folate biosynthesis. Furthermore, the expression levels of traumatic acid, traumatin, alpha linolenic acid, cholic acid, 2-arachidonoylglycerol, deoxycholic acid, 7,8-dihydroneopterin, and other metabolites were found to be regulated. CONCLUSION: FNKL exhibits positive therapeutic effects on CB, with quercetin-3-galactoside identified as a key active component. The mechanism of FNKL's therapeutic action on CB involves reducing inflammatory response, oxidative stress, and regulating metabolism, and its molecular mechanism was better elucidated in a holistic manner. This study serves as a reference for understanding the pharmacodynamic material basis and mechanism of action of FNKL in treating CB, and provides avenues for exploring the effects of compounded herbal medicines on CB.

Hydrogen-Bonded Organic Frameworks-based Electrolytes with Controllable Hydrogen Bonding Networks for Solid-State Lithium Batteries.

The lack of stable solid-state electrolytes (SSEs) with high-ionic conductivity and rational design of electrode/electrolyte interfaces remains challenging for solid-state lithium batteries. Here, for the first time, a high-performance solid-state lithium-oxygen battery is developed based on the Li-ion-conducted hydrogen-bonded organic framework (LHOF) electrolyte and the core-shell HOF-DAT@CNT cathode with a few layers of HOF-DAT on surface of carbon nanotubes. Benefiting from the abundant dynamic hydrogen bonding network in LHOF-DAT SSEs, fast Li+ ion transport (2.2 × 10-4 S cm-1), a high Li+ transfer number (0.88), and a wide electrochemical window of 5.05 V are achieved. Symmetric batteries constructed with LHOF-DAT SSEs exhibit a stably cycled duration of over 1400 h, which mainly stems from the jumping sites that promote a uniformly high rate of Li+ flux and the hydrogen-bonding network structure that can relieve the structural changes during Li+ transport. LHOF-DAT SSEs-based Li-O2 batteries exhibit high specific capacity (10335 mAh g-1), and stable cycling life up to 150 cycles. Moreover, the solid-state lithium metal battery with LHOF-DAT SSEs endow good rate capability (128.8 mAh g-1 at 1 C), long-term discharge/charge stability (210 cycles). The design of LHOF-DAT SSEs opens an avenue for the development of novel SSEs-based solid-state lithium batteries.

Assessing next-generation sequencing-based computational methods for predicting transcriptional regulators with query gene sets.

This article provides an in-depth review of computational methods for predicting transcriptional regulators (TRs) with query gene sets. Identification of TRs is of utmost importance in many biological applications, including but not limited to elucidating biological development mechanisms, identifying key disease genes, and predicting therapeutic targets. Various computational methods based on next-generation sequencing (NGS) data have been developed in the past decade, yet no systematic evaluation of NGS-based methods has been offered. We classified these methods into two categories based on shared characteristics, namely library-based and region-based methods. We further conducted benchmark studies to evaluate the accuracy, sensitivity, coverage, and usability of NGS-based methods with molecular experimental datasets. Results show that BART, ChIP-Atlas, and Lisa have relatively better performance. Besides, we point out the limitations of NGS-based methods and explore potential directions for further improvement.

Constituents from Dendrobium aphyllum: Bibenzyls, furfurals, phenanthrenes, and phenylpropanoids and their antioxidant and anti-inflammatory potentials.

Chemical investigation on the aqueous extract of Dendrobium aphyllum led to the isolation of thirty-one constituents with structures identified by analysis of the extensive spectroscopic data (1D/2D NMR, MS, UV, and ECD), including previously undescribed two bibenzyls, one furfural, and one phenolic acid, namely trigonopol D (1), trigonopol C (2), dendrofunan A (10), and 6-(4-hydroxy-3-methoxyphenyl)-3,6-dioxohexyl acetate (30), respectively, as well as twenty-seven known ones. Among them, there were one new natural product (11), seven compounds (6-7, 9, 12, 20, 28, 31) described from the genus Dendrobium for the first time, and fifteen compounds (8, 13-17, 19, 21-27, 29) isolated from D. aphyllum for the first time. Further, the antioxidant and anti-inflammatory potentials of fifteen compounds (4-5, 8, 11-12, 14-19, 22, 24, 26, and 29) with significant scavenging capacities against DPPH and hydroxyl radicals, and virtual docking activities inhibiting COX-2 and 5-LOX, respectively. Our study may draw the attention of medicinal plant taxonomists and supply potential quality markers for discrimination of D. aphyllum from other species in Dendrobium genus.

MFRP variations cause nanophthalmos in five Chinese families with distinct phenotypic diversity.

Purpose: Nanophthalmos is a congenital ocular structural anomaly that can cause significant visual loss in children. The early diagnosis and then taking appropriate clinical and surgical treatment remains a challenge for many ophthalmologists because of genetic and phenotypic heterogeneity. The objective of this study is to identify the genetic cause of nanophthalmos in the affected families and analyze the clinical phenotype of nanophthalmos with MFRP gene variation (Microphthalmia, isolated; OMIM#611040 and Nanophthalmos 2; OMIM#609549, respectively). Methods: Comprehensive ophthalmic examinations were performed on participants to confirm the phenotype. The genotype was identified using whole exome sequencing, and further verified the results among other family members by Sanger sequencing. The normal protein structure was constructed using Alphafold. Mutant proteins were visualized using pymol software. Pathogenicity of identified variant was determined by in silico analysis and the guidelines of American College of Medical Genetics and Genomics (ACMG). The relationship between genetic variants and clinical features was analyzed. Results: Five nanophthalmos families were autosomal recessive, of which four families carried homozygous variants and one family had compound heterozygous variants in the MFRP gene. Both family one and family three carried the homozygous missense variant c.1486G>A (p.Glu496Lys) in the MFRP gene (Clinvar:SCV005060845), which is a novel variant and evaluated as likely pathogenic according to the ACMG guidelines and in silico analysis. The proband of family one presented papilloedema in both eyes, irregular borders, thickened retinas at the posterior pole, tortuous and dilated retinal vessels, and indistinguishable arteries and veins, while the proband of family three presented uveal effusion syndrome-like changes in the right eye. In families one and 3, despite carrying the same gene variant, the probands had completely different clinical phenotypes. The homozygous nonsense variant c.271C>T (p.Gln91Ter) (Clinvar:SCV005060846) of the MFRP gene was detected in family 2, presenting shallow anterior chamber in both eyes, pigmentation of peripheral retina 360° from the equator to the serrated rim showing a clear demarcation from the normal retina in the form of strips. Family four proband carried the homozygous missense variant c.1411G>A (p.Val471Met) in the MFRP gene (Clinvar:SCV005060847), family five proband carried compound heterozygous missense variants c.1486G>A (p.Glu496Lys) and c.602G>T (p.Arg201Leu) in the MFRP gene (Clinvar:SCV005060848), which is a novel variant and evaluated as likely pathogenic according to the ACMG guidelines and in silico analysis, and they all presented clinically with binocular angle-closure glaucoma, family four also had retinal vein occlusion in the right eye during the follow-up. Conclusion: In this study, pathogenic variants of the MFRP gene were detected in five nanophthalmos families, including two novel variants. It also revealed a distinct phenotypic diversity among five probands harboring variants in the MFRP gene. Our findings extend the phenotype associated with MFRP variants and is helpful for ophthalmologists in early diagnosis and making effective treatment and rehabilitation strategies.

Microbial interactions in mixed-species biofilms on the surfaces of Baijiu brewing environments.

Environmental microorganisms commonly inhabit dense multispecies biofilms, fostering mutualistic relationships and co-evolution. However, the mechanisms underlying biofilm formation and microbial interactions within the Baijiu fermentation microecosystem remain poorly understood. Hence, the objective of this study was to investigate the composition, structure, and interactions of microorganisms residing in biofilms on environmental surfaces in Baijiu production. The results revealed a shift in the bacteria-fungi interaction network following fermentation, transitioning from a cooperative/symbiotic relationship to a competitive/antagonistic dynamic. Core microbiota within the biofilms comprised lactic acid bacteria (LAB), yeast, and filamentous fungi. From the environmental surface samples, we isolated two strains of LAB (Lactiplantibacillus pentosus EB27 and Pediococcus pentosaceus EB35) and one strain of yeast (Pichia kudriavzevii EF8), all displaying remarkable biofilm formation and fermentation potential. Co-culturing LAB and yeast demonstrated a superior capacity for dual-species biofilm formation compared to mono-species biofilms. The dual-species biofilm displayed a two-layer structure, with LAB in the lower layer and serving as the foundation for the yeast community in the upper layer. The upper layer exhibited a dense distribution of yeast, enhancing aerobic respiration. Metabolic activities in the dual-species biofilm, such as ABC transporter, oxidative phosphorylation, citric acid cycle, sulfur metabolism, glycine, serine, threonine metabolism, lysine degradation, and cysteine and methionine metabolism, showed significant alterations compared to LAB mono-species biofilms. Moreover, bacterial chemotaxis, starch, and sucrose metabolism in the dual-species biofilm exhibited distinct patterns from those observed in the yeast mono-species biofilm. This study demonstrated that a core microbiota with fermentation potential may exist in the form of a biofilm on the surface of a Baijiu brewing environment. These findings provide a novel strategy for employing synthetic stable microbiotas in the intelligent brewing of Baijiu.

Silk-based intelligent fibers and textiles: structures, properties, and applications.

Multifunctional fibers represent a cornerstone of human civilization, playing a pivotal role in numerous aspects of societal development. Natural biomaterials, in contrast to synthetic alternatives, offer environmental sustainability, biocompatibility, and biodegradability. Among these biomaterials, natural silk is favored in biomedical applications and smart fiber technology due to its accessibility, superior mechanical properties, diverse functional groups, controllable structure, and exceptional biocompatibility. This review delves into the intricate structure and properties of natural silk fibers and their extensive applications in biomedicine and smart fiber technology. It highlights the critical significance of silk fibers in the development of multifunctional materials, emphasizing their mechanical strength, biocompatibility, and biodegradability. A detailed analysis of the hierarchical structure of silk fibers elucidates how these structural features contribute to their unique properties. The review also encompasses the biomedical applications of silk fibers, including surgical sutures, tissue engineering, and drug delivery systems, along with recent advancements in smart fiber applications such as sensing, optical technologies, and energy storage. The enhancement of functional properties of silk fibers through chemical or physical modifications is discussed, suggesting broader high-end applications. Additionally, the review addresses current challenges and future directions in the application of silk fibers in biomedicine and smart fiber technologies, underscoring silk's potential in driving contemporary technological innovations. The versatility and sustainability of silk fibers position them as pivotal elements in contemporary materials science and technology, fostering the development of next-generation smart materials.

Integrated cell wall and transcriptomic analysis revealed the mechanism underlying zinc-induced alleviation of cadmium toxicity in Cosmos bipinnatus.

Plant growth is severely harmed by cadmium (Cd) contamination, while the addition of zinc (Zn) can reduce the toxic effects of Cd. However, the interaction between Cd and Zn on the molecular mechanism and cell wall of Cosmosbipinnatus is unclear. In this study, a transcriptome was constructed using RNA-sequencing. In C. bipinnatus root transcriptome data, the expression of 996, 2765, and 3023 unigenes were significantly affected by Cd, Zn, and Cd + Zn treatments, respectively, indicating different expression patterns of some metal transporters among the Cd, Zn, and Cd + Zn treatments. With the addition of Zn, the damage to the cell wall was reduced, both the proportion and content of polysaccharides in the cell wall were changed, and Cd accumulation was decreased by 32.34%. In addition, we found that Cd and Zn mainly accumulated in pectins, the content of which increased by 30.79% and 61.4% compared to the CK treatment. Thus, Zn could alleviate the toxicity of Cd to C. bipinnatus. This study revealed the interaction between Cd and Zn at the physiological and molecular levels, broadening our understanding of the mechanisms of tolerance to Cd and Zn stress in cosmos.

Cell-based therapy for diabetic cardiovascular complications: Prospects and challenges.

Diabetes mellitus is a long-term metabolic condition characterized by high blood glucose levels. This disorder is closely associated with a range of complications affecting small and large blood vessels, including conditions like retinopathy, nephropathy and neuropathy, as well as ischaemic heart disease, peripheral vascular disease and cerebrovascular disease. These complications cause organ and tissue damage in an estimated 33% to 50% of individuals with diabetes. The management of these complications in patients with diabetes is confronted with significant clinical challenges. Present treatment modalities for cardiovascular complications secondary to diabetes are limited and exhibit suboptimal efficacy. Cell-based therapies has shown great promise in regenerative medicine and improving cardiovascular function in individuals with diabetic complications, attributed to their potential for multilineage differentiation and regenerative capacity. In this review, we focus on diabetic cardiovascular complications and provide a brief introduction to the application of cell-based therapies, including the use of stem cells and progenitor cells, their mechanisms of action and the prospects and challenges.

Aliphatic Hydrosilanes via Nickel-Catalyzed Reductive Csp3-Si Coupling of Primary Alkyl Bromides and Chlorohydrosilanes.

The reductive C-Si coupling of chlorosilanes offers efficient access to organosilanes, but its potential for constructing aliphatic ones remains largely unexplored. This manuscript presents a nickel-catalyzed Csp3-Si coupling reaction of unactivated alkyl-Br and R2Si(H)Cl. This work establishes a new approach for synthesizing highly functionalized aliphatic hydrosilanes from readily available chemical feedstocks. The reaction is easily scalable and can accommodate various functional groups, including carboxylic acids, which are usually incompatible with basic conditions.

Cost-effectiveness analysis of camrelizumab plus paclitaxel and carboplatin versus sintilimab plus gemcitabine and cisplatin or carboplatin for the first-line treatment of local advanced or metastatic squamous NSCLC in Chinese mainland.

Objective: Both camrelizumab plus paclitaxel and carboplatin (CTC) and sintilimab plus gemcitabine and cisplatin or carboplatin (SGP) have been approved by the National Medical Products Administration of China (NMPA) for the first-line treatment of local advanced or metastatic sqNSCLC. However, the comparison of the two treatments as first-line treatments in efficacy or pharmacoeconomics has barely been studied. To deeply understand the costs and outcomes of the two treatments, this work directly compared the cost-effectiveness for the first-line treatment of local advanced or metastatic squamous NSCLC in the Chinese mainland. Methods: A network meta-analysis was first performed based on the three clinical trials, namely, CameL-Sq, ORIENT-12, and C-TONG1002, to compare the clinical benefits of the two treatments. The Weibull approximation was applied to further calculate the life expectancy of the two treatments. The partitioned survival model (PSM) was next established, and one-way sensitivity analysis and probabilistic sensitivity analysis were also performed to evaluate the stability of the underlying parameter values and assumptions within the model. Results: CTC treatment gained 0.68 QALYs and cost $14,764. SGP treatment gained 0.54 QALYs and cost $14,584. The CTC arm gained 0.14 additional QALYs and cost $179 more than the SGP arm, and the ICERs was $1,269/QALY, which was lower than one-fold GDP per capita in the Chinese mainland ($12,734 GDP per capita in 2022). In probabilistic sensitivity analysis, when the WTP ranged from $12,734-38,202 (1-3 folds, 2022 GDP per capita in China), the CTC group had higher probabilities than the SGP group for being cost effective, which ranged from 85.65% to 88.38%. Conclusion: From the perspective of the payers, camrelizumab plus chemotherapy was cost-effective compared with sintilimab plus chemotherapy for the first-line treatment of local advanced or metastatic squamous NSCLC in the Chinese mainland.