Prussian Blue Nanohybridized Multicellular Spheroids as Composite Engraftment for Antioxidant Bone Regeneration and Photoacoustic Tomography.

Regulating the complex microenvironment after tooth extraction to promote alveolar bone regeneration is a pressing challenge for restorative dentistry. In this study, through modulating the mechanical properties of the cellular matrix, we guided various types of cells by self-organizing to form multicellular spheroids (MCSs) and hybridized MCSs with Prussian Blue nanoparticles (PBNPs) in the process. The constructed Prussian Blue nanohybridized multicellular spheroids (PBNPs@MCSs) with empowered antioxidant functions effectively reduced cell apoptosis under peroxidative conditions and exhibited enhanced ability to regulate the microenvironment and promote bone repair both in vitro and in vivo. In addition, the PBNPs@MCSs exhibited enhanced photoacoustic imaging ability to trace low doses of PBNPs. Therefore, the constructed PBNPs@MCSs based on the biomimetic hydrogel can be used as a form of an engraftment building block, with a greater potential for pro-bone repair application in the complex microenvironment of the oral cavity.

Exploring anisotropic mechanical properties of lobster claw exoskeleton through fractal models.

The outstanding mechanical properties of lobster claw exoskeletons are intricately tied to their internal microstructure. Investigating this relationship can offer vital insights for designing high-performance additive manufacturing structures. Fractal theory, with its fractional dimensional perspective, suits the complexity of real-world phenomena. Our study examines fully hydrated lobster claw exoskeletons using a multifaceted approach: four-point bending tests, scanning electron microscopy observations, and fractal models. Test results reveal superior mechanical properties in longitudinal specimens. Scanning electron microscopy shows non-uniform fiber helical structures and porous elements in the exoskeleton. Fracture mechanisms involve both breaking fiber fragments perpendicular to the cross-section and tearing between these fragments. The observed crack propagation paths exhibit statistical self-similarity. Consequently, we develop fractal models for the crack propagation paths in longitudinal and transverse specimens, calculating crack extension forces. Using the box-counting method and its improved variant, we determine the fractal dimensions of specimen sections. The fractal dimension of longitudinal models exceeds that of transverse models, and calculated crack extension forces are higher in longitudinal models. These findings align well with experimental data, demonstrating fractal theory's efficacy in analyzing the lobster claw exoskeleton's anisotropic mechanical properties.

The Potential Correlation between Bacterial Diversity and the Characteristic Volatile Flavor Compounds of Sichuan Sauce-Flavored Sausage.

The distinctive taste of Sichuan sauce-flavored sausage comes from an intricate microbial metabolism. The correlation between microbial composition and distinct flavor components has not been researched. The study used headspace solid-phase microextraction action with gas chromatography mass spectrometry to find flavor components and high-throughput sequencing of 16S rRNA to look at the diversity and succession of microbial communities. The correlation network model forecasted the connection between essential bacteria and the development of flavors. The study revealed that the primary flavor compounds in Sichuan sauce-flavored sausages were alcohols, aldehydes, and esters. The closely related microbes were Leuconostoc, Pseudomonas, Psychrobacter, Flavobacterium, and Algoriella. The microbes aided in the production of various flavor compounds, such as 1-octen-3-ol, benzeneacetaldehyde, hexanal, (R,R)-2,3-butanediol, and ethyl caprylate. This work has enhanced our comprehension of the diverse functions that bacteria serve in flavor development during the fermentation of Sichuan sauce-flavored sausage.

Research Progress on Bacteria-Reducing Pretreatment Technology of Meat.

Reducing the initial bacteria number from meat and extending its shelf life are crucial factors for ensuring product safety and enhancing economic benefits for enterprises. Currently, controlling enzyme activity and the microbial survival environment is a common approach to reducing the rate of deterioration in raw meat materials, thereby achieving the goal of bacteria reduction during storage and preservation. This review summarizes the commonly used technologies for reducing bacteria in meat, including slightly acidic electrolyzed water (SAEW), organic acids, ozone (O3), ultrasound, irradiation, ultraviolet (UV), cold plasma, high-pressure processing (HPP), and biological bacterial reduction agents. This review outlines the mechanisms and main features of these technologies for reducing bacteria in meat processing. Additionally, it discusses the status of these technologies in meat storage and preservation applications while analyzing associated problems and proposing solutions. The aim is to provide valuable references for research on meat preservation technology.

Influence of Penicillium lanosum and Staphylococcus equorum on Microbial Diversity and Flavor of Mianning Hams.

Mianning ham is a traditional meat product in China. In this experiment, solid-phase microextraction-gas chromatography (SPME-GC-MS) and high-throughput sequencing were used to study the effects of adding Penicillium lanosum and adding the mixture of Penicillium lanosum and Staphylococcus equorum on the flavor and microbiology of Mianning ham. The results showed that the addition of the ferments resulted in an increase in the abundance of both the dominant bacterial phylum (Thick-walled Bacteria) and the dominant fungal phylum (Ascomycota). The variety of volatile flavor substances and key flavor substances increased after adding fermentation agents. A free amino acid analysis showed that hams from the Penicillium lanosum and Staphylococcus equorum group had significantly higher umami flavor amino acids than the control group and Penicillium lanosum group. Therefore, inoculation with Penicillium lanosum and Staphylococcus equorum favored the dominant bacteria and flavor of Mianning ham.

Study on the Changes and Correlation of Microorganisms and Flavor in Different Processing Stages of Mianning Ham.

(1) Background: Mianning ham is a dry-cured ham from Southwest China, known for its distinct regional characteristics and delicious taste. It is particularly favored by consumers due to its safety, as no artificial nitrites are added during processing. The microbial changes during its different processing stages significantly influence the final product's flavor. This study aims to investigate the changes in microbial communities and flavor compounds across the nine stages of Mianning ham production, from raw material preparation to salting, drying, fermentation, and maturation, using 16S and ITS sequencing, as well as solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS). The goal is to explore the correlation between these changes and provide a basis for process improvement from the initial raw material preparation. (2) Results: The microbiota of Mianning ham across different processing stages mainly consisted of Proteobacteria, Firmicutes, and Ascomycota. A total of 324 volatile compounds were identified, of which 27 were key contributors to the ham's flavor. Aldehydes contributed the most to flavor, with octanal, trans-2-nonenal, and trans, trans-2,4-decadienal being the most significant contributors at various stages. Mature Mianning ham, fermented for 1-3 years, exhibited fresh grass and earthy aromas, buttery and fatty flavors, and a distinctive roasted potato note. Correlation analysis revealed that Cobetia was the primary bacterial contributor to the main flavor compounds, especially prominent in the second year of fermentation. Among fungi, Yamadazyma and Aspergillus positively influenced several key aldehyde flavor compounds throughout the processing stages, significantly contributing to the flavor profile of Mianning ham. (3) Conclusions: Correlation analysis showed that the Mianning ham that matured for two years had the richest and most characteristic flavor. The positive and consistent impact of fungi on the ham's flavor suggests that they may warrant further research and application in Mianning ham production. This provides a theoretical basis for improving the flavor quality and enhancing the market competitiveness of Mianning ham. One of the key features of Mianning ham is its substantial accumulation of hydrocarbons, which surpasses that of hams from other regions in China. A notable characteristic of Mianning ham processing is the absence of artificially added nitrites as antioxidants and color fixatives. Whether this absence is a contributing factor to the significant accumulation of hydrocarbons warrants further investigation.

Circular RNA-based therapy provides sustained and robust neuroprotection for retinal ganglion cells.

Ocular neurodegenerative diseases like glaucoma lead to progressive retinal ganglion cell (RGC) loss, causing irreversible vision impairment. Neuroprotection is needed to preserve RGCs across debilitating conditions. Nerve growth factor (NGF) protein therapy shows efficacy, but struggles with limited bioavailability and a short half-life. Here we explore a novel approach to address this deficiency by utilizing circular RNA (circRNA)-based therapy. We show that circRNAs exhibit an exceptional capacity for prolonged protein expression and circRNA-expressed NGF protects cells from glucose deprivation. In a mouse optic nerve crush model, lipid nanoparticle (LNP)-formulated circNGF administered intravitreally protects RGCs and axons from injury-induced degeneration. It also significantly outperforms NGF protein therapy without detectable retinal toxicity. Furthermore, single-cell transcriptomics revealed LNP-circNGF's multifaceted therapeutic effects, enhancing genes related to visual perception while reducing trauma-associated changes. This study signifies the promise of circRNA-based therapies for treating ocular neurodegenerative diseases and provides an innovative intervention platform for other ocular diseases.

Film-Forming Capability and Antibacterial Activity of Surface-Deacetylated Chitin Nanocrystals: Role of Degree of Deacetylation.

Developing sustainable food-active packaging materials is a major issue in food preservation applications. Chitin nanocrystals (ChNCs) are regarded as unique bioderived nanomaterials due to their inherent nitrogen moiety. By tuning the chemical functionality of this nanomaterial, it is possible to affect its properties, such as film-forming capability and antibacterial activity. In this work, surface-deacetylated chitin nanocrystals (D-ChNCs) with different degrees of deacetylation (DDs) were prepared by partial deacetylation of native chitin and subsequent acid hydrolysis, and their film-forming capability and antibacterial activity were studied systematically. The D-ChNCs showed favorable film-forming ability and antibacterial activity, which are closely related to their DD. With the increase in DD (from 5.7% to 45.4%), the formed transparent films based on ChNCs showed gradually increased elongation at break (from 0.5% to 2.5%) and water contact angle (from 25.5° to 87.0°), but decreased break strength (from 3.13 to 0.89 MPa), Young's modulus (from 0.84 to 0.24 MPa), and water vapor permeability (from 4.7 × 10-10 to 4.1 × 10-10g/m s Pa). Moreover, the antibacterial activity of the D-ChNCs against E. coli and S. aureus also increased with the increase of DD. This study also found that the depolarization and potential dissipation of the bacterial cell membrane induced by the contact between amino-rich D-ChNCs and bacteria through electrostatic attraction are the possible mechanisms causing bacterial cell death. This study provides a basis for understanding the effects of DD on the film-forming capability and antibacterial activity of ChNCs, which is conducive to the design of novel active packaging films based on ChNCs.

Multifunctional Glycopeptide-Based Hydrogel via Dual-Modulation for the Prevention and Repair of Radiation-Induced Skin Injury.

The radiation-induced skin injury (RISI) remains a great challenge for clinical wound management and care after radiotherapy, as patients will suffer from the acute radiation injury and long-term chronic inflammatory damage during the treatment. The excessive ROS in the early acute stage and prolonged inflammatory response in the late healing process always hinder therapeutic efficiency. Herein, we developed an extracellular matrix (ECM)-mimetic multifunctional glycopeptide hydrogel (oCP@As) to promote and accelerate RISI repair via a dual-modulation strategy in different healing stages. The oCP@As hydrogel not only can form an ECM-like nanofiber structure through the Schiff base reaction but also exhibits ROS scavenging and DNA double-strand break repair abilities, which can effectively reduce the acute radiation damage. Meanwhile, the introduction of oxidized chondroitin sulfate, which is the ECM polysaccharide-like component, enables regulation of the inflammatory response by adsorption of inflammatory factors, accelerating the repair of chronic inflammatory injury. The animal experiments demonstrated that oCP@As can significantly weaken RISI symptoms, promote epidermal tissue regeneration and angiogenesis, and reduce pro-inflammatory cytokine expression. Therefore, this multifunctional glycopeptide hydrogel dressing can effectively attenuate RISI symptoms and promote RISI healing, showing great potential for clinical applications in radiotherapy protection and repair.

A glycopolymersome strategy for 'drug-free' treatment of diabetic nephropathy.

Diabetic nephropathy is a severe complication of diabetes. Treatment of diabetic nephropathy is an important challenge due to persistent hyperglycemia and elevated levels of reactive oxygen species (ROS) in the kidney. Herein, we designed a glycopolymersome that can treat type 2 diabetic nephropathy by effectively inhibiting hyperglycemia and ROS-associated diabetic nephropathy pathogenesis. The glycopolymersome is self-assembled from phenylboronic acid derivative-containing copolymer, poly(ethylene oxide)45-block-poly[(aspartic acid)13-stat-glucosamine24-stat-(phenylboronic acid)18-stat-(phenylboronic acid pinacol ester)3] [PEO45-b-P(Asp13-stat-GA24-stat-PBA18-stat-PAPE3)]. PBA segment can reversibly bind blood glucose or GA segment for long-term regulation of blood glucose levels; PAPE segment can scavenge excessive ROS for renoprotection. In vitro studies confirmed that the glycopolymersomes exhibit efficient blood glucose responsiveness within 2 h and satisfactory ROS-scavenging ability with 500 µM H2O2. Moreover, the glycopolymersomes display long-acting regulation of blood glucose levels in type 2 diabetic nephropathy mice within 32 h. Dihydroethidium staining revealed that these glycopolymersomes reduced ROS to normal levels in the kidney, which led to 61.7% and 76.6% reduction in creatinine and urea levels, respectively, along with suppressing renal apoptosis, collagen accumulation, and glycogen deposition in type 2 diabetic nephropathy mice. Notably, the polypeptide-based glycopolymersome was synthesized by ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs), thereby exhibiting favorable biodegradability. Overall, we proposed a new glycopolymersome strategy for 'drug-free' treatment of diabetic nephropathy, which could be extended to encompass the design of various multifunctional nanoparticles targeting diabetes and its associated complications.

Biodegradable quaternized silk fibroin sponge with highly uniform pore structure for traumatic hemostasis and anti-infection.

Developing a biodegradable sponge with rapid shape recovery and potent antibacterial and coagulation properties for traumatic hemostasis and anti-infection remains challenging. Herein, we fabricated quaternized silk fibroin (SF) sponges by freeze-drying under a constant cooling rate and modification with quaternary ammonium groups. We found the constant cooling rate enabled the sponges with a highly uniform pore structure, which provided excellent self-elasticity and shape recovery. Decoration with quaternary ammonium groups enhanced blood cells adhesion, aggregation, and activation, as well as resistance to infections from Staphylococcus aureus and Escherichia coli. The SF sponge had superior hemostatic capacity to gauze and commercial gelatin sponge in different hemorrhage models. The SF sponge exhibited favorable biodegradability and biocompatibility. Moreover, The SF sponge also promoted host cell infiltration, capillary formation, and tissue ingrowth, suggesting its potential for guiding tissue regeneration. The developed SF sponge holds great application prospects for traumatic hemostasis, anti-infection, and guiding tissue regeneration.

Sulforaphane enhanced muscle growth by promoting lipid oxidation through modulating key signaling pathways.

Sulforaphane (SFN) has shown diverse effects on human health and diseases. SFN was administered daily to C57BL/6J mice at doses of 1 mg/kg (SFN1) and 3 mg/kg (SFN3) for 8 weeks. Both doses of SFN accelerated body weight increment. The cross-sectional area and diameter of Longissimus dorsi (LD) muscle fibers were enlarged in SFN3 group. Triglyceride (TG) and total cholesterol (TC) levels in LD muscle were decreased in SFN groups. RNA sequencing results revealed that 2455 and 2318 differentially expressed genes (DEGs) were found in SFN1 and SFN3 groups, respectively. Based on GO enrichment analysis, 754 and 911 enriched GO terms in the SFN1 and SFN3 groups, respectively. KEGG enrichment analysis shown that one KEGG pathway was enriched in the SFN1 group, while six KEGG pathways were enriched in the SFN3 group. The expressions of nine selected DEGs validated with qRT-PCR were in line with the RNA sequencing data. Furthermore, SFN treatment influenced lipid and protein metabolism related pathways including AMPK signaling, fatty acid metabolism signaling, cholesterol metabolism signalling, PPAR signaling, peroxisome signaling, TGFß signaling, and mTOR signaling. In summary, SFN elevated muscle fibers size and reduced TG and TC content of in LD muscle by modulating protein and lipid metabolism-related signaling pathways.

Study on simulation effect of physical and chemical characteristics of sausage by sausage model system.

Introduction: The incorporation of Staphylococcus xylosus in sausage production is hypothesized to affect various physicochemical properties and flavor profiles of sausages. This study aimed to evaluate the simulation of these features in a sausage model and establish its applicability for in vitro studies. Methods: Both a control and an experimental model, inclusive of Staphylococcus xylosus, were assessed for changes in physicochemical indexes (pH and water activity, Aw) and the concentration of flavoring components (esters and aldehydes). Thiobarbituric acid reactive substances (TBARS) values were also measured to evaluate lipid oxidation. Results: The introduction of Staphylococcus xylosus resulted in no significant changes in pH and Aw between the sausage and the model. However, there was a considerable increase in the content of volatile flavor compounds, specifically esters and aldehydes, in the experimental groups compared to the control. Additionally, the TBARS values in experimental groups were significantly lower than those in the control group at the end of the testing period. Discussion: The findings indicate that Staphylococcus xylosus plays a critical role in enhancing the flavor profile of sausages through the increased synthesis of volatile compounds and inhibiting fat oxidation. The sausage model effectively simulated the physicochemical and flavor index responses, demonstrating its potential utility for further in vitro research on sausage fermentation and preservation techniques.

Abnormal trial-to-trial variability in P300 time-varying directed eeg network of schizophrenia.

Cognitive disturbance in identifying, processing, and responding to salient or novel stimuli are typical attributes of schizophrenia (SCH), and P300 has been proven to serve as a reliable psychosis endophenotype. The instability of neural processing across trials, i.e., trial-to-trial variability (TTV), is getting increasing attention in uncovering how the SCH "noisy" brain organizes during cognition processes. Nevertheless, the TTV in the brain network remains unrevealed, notably how it varies in different task stages. In this study, resorting to the time-varying directed electroencephalogram (EEG) network, we investigated the time-resolved TTV of the functional organizations subserving the evoking of P300. Results revealed anomalous TTV in time-varying networks across the delta, theta, alpha, beta1, and beta2 bands of SCH. The TTV of cross-band time-varying network properties can efficiently recognize SCH (accuracy: 83.39%, sensitivity: 89.22%, and specificity: 74.55%) and evaluate the psychiatric symptoms (i.e., Hamilton's depression scale-24, r = 0.430, p = 0.022, RMSE = 4.891; Hamilton's anxiety scale-14, r = 0.377, p = 0.048, RMSE = 4.575). Our study brings new insights into probing the time-resolved functional organization of the brain, and TTV in time-varying networks may provide a powerful tool for mining the substrates accounting for SCH and diagnostic evaluation of SCH.

Recent advances and challenges in the interaction between myofibrillar proteins and flavor substances.

Myofibrillar proteins are an important component of proteins. Flavor characteristics are the key attributes of food quality. The ability of proteins to bind flavor is one of their most fundamental functional properties. The dynamic balance of release and retention of volatile flavor compounds in protein-containing systems largely affects the sensory quality and consumer acceptability of foods. At present, research on flavor mainly focuses on the formation mechanism of flavor components, while there are few reports on the release and perception of flavor components. This review introduces the composition and structure of myofibrillar proteins, the classification of flavor substances, the physical binding and chemical adsorption of myofibrillar proteins and volatile flavor substances, as well as clarifies the regulation law of flavor substances from the viewpoint of endogenous flavor characteristics and exogenous environment factors, to provide a theoretical reference for the flavor regulation of meat products.

Heme-Mimetic Photosensitizer with Iron-Targeting and Internalizing Properties for Enhancing PDT Activity and Promoting Infected Diabetic Wound Healing.

The management of multibacterial infections remains clinically challenging in the care and treatment of chronic diabetic wounds. Photodynamic therapy (PDT) offers a promising approach to addressing bacterial infections. However, the limited target specificity and internalization properties of traditional photosensitizers (PSs) toward Gram-negative bacteria pose significant challenges to their antibacterial efficacy. In this study, we designed an iron heme-mimetic PS (MnO2@Fe-TCPP(Zn)) based on the iron dependence of bacteria that can be assimilated by bacteria and retained in different bacteria strains (Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus) and which shows high PDT antibacterial efficacy. For accelerated wound healing after antibacterial treatment, MnO2@Fe-TCPP(Zn) was loaded into a zwitterionic hydrogel with biocompatibility and antifouling properties to form a nanocomposite antibacterial hydrogel (PSB-MnO2@Fe-TCPP(Zn)). In the multibacterial infectious diabetic mouse wound model, the PSB-MnO2@Fe-TCPP(Zn) hydrogel dressing rapidly promoted skin regeneration by effectively inhibiting bacterial infections, eliminating inflammation, and promoting angiogenesis. This study provides an avenue for developing broad-spectrum antibacterial nanomaterials for combating the antibiotic resistance crisis and promoting the healing of complex bacterially infected wounds.

Interlayer Polymerization to Construct a Fully Conjugated Covalent Organic Framework as a Metal-Free Oxygen Reduction Reaction Catalyst for Anion Exchange Membrane Fuel Cells.

Two-dimensional (2D) covalent organic frameworks (COFs) have a multilayer skeleton with a periodic π-conjugated molecular array, which can facilitate charge carrier transport within a COF layer. However, the lack of an effective charge carrier transmission pathway between 2D COF layers greatly limits their applications in electrocatalysis. Herein, by employing a side-chain polymerization strategy to form polythiophene along the nanochannels, a conjugated bridge is constructed between the COF layers. The as-synthesized fully conjugated COF (PTh-COF) exhibits high oxygen reduction reaction (ORR) activity with narrowed energy band gaps. Correspondingly, PTh-COF is tested as a metal-free cathode catalyst for anion exchange membrane fuel cells (AEMFCs) which showed a maximum power density of 176 mW cm-2 under a current density of 533 mA cm-2. The density functional theory (DFT) calculation reveals that interlayer conjugated polythiophene optimizes the electron cloud distribution, which therefore enhances the ORR performance. This work not only provides new insight into the construction of a fully conjugated covalent organic framework but also promotes the development of new metal-free ORR catalysts.

Osthole ameliorates early diabetic kidney damage by suppressing oxidative stress, inflammation and inhibiting TGF-ß1/Smads signaling pathway.

BACKGROUND: Osthole is a natural active ingredient extracted from the traditional Chinese medicine Cnidium monnieri. It has been demonstrated to have anti-inflammatory, anti-fibrotic, and anti-hyperglycemic properties. However, its effect on diabetic kidney disease (DKD) remains uncertain. This study aims to assess the preventive and therapeutic effects of osthole on DKD and investigate its underlying mechanisms. METHODS: A streptozotocin/high-fat and high-sucrose diet induced Type 2 diabetic rat model was established. Metformin served as the positive drug control. Diabetic rats were treated with metformin or three different doses of osthole for 8 weeks. Throughout the treatment period, the progression of DKD was assessed by monitoring increases in urinary protein, serum creatinine, urea nitrogen, and uric acid, along with scrutinizing kidney pathology. Enzyme-linked immunosorbent assay (ELISA) was employed to detect inflammatory factors and oxidative stress levels. At the same time, immunohistochemical staining was utilized to evaluate changes in alpha-smooth muscle actin, fibronectin, E-cadherin, and apoptosis. The alterations in TGF-ß1/Smads signaling pathway were ascertained through western blot and immunofluorescence. Furthermore, we constructed a high glucose-stimulated HBZY-1 cells model to uncover its molecular protective mechanism. RESULTS: Osthole significantly reduced fasting blood glucose, insulin resistance, serum creatinine, uric acid, blood urea nitrogen, urinary protein excretion, and glomerular mesangial matrix deposition in diabetic rats. Additionally, significant improvements were observed in inflammation, oxidative stress, apoptosis, and fibrosis levels. The increase of ROS, apoptosis and hypertrophy in HBZY-1 cells induced by high glucose was reduced by osthole. Immunofluorescence and western blot results demonstrated that osthole down-regulated the TGF-ß1/Smads signaling pathway and related protein expression. CONCLUSION: Our findings indicate that osthole exhibits potential preventive and therapeutic effects on DKD. It deserves further investigation as a promising drug for preventing and treating DKD.

Gut bacterial and fungal dysbiosis in tuberculosis patients.

BACKGROUND: Recent studies have more focused on gut microbial alteration in tuberculosis (TB) patients. However, no detailed study on gut fungi modification has been reported till now. So, current research explores the characteristics of gut microbiota (bacteria)- and mycobiota (fungi)-dysbiosis in TB patients and also assesses the correlation between the gut microbiome and serum cytokines. It may help to screen the potential diagnostic biomarker for TB. RESULTS: The results show that the alpha diversity of the gut microbiome (including bacteria and fungi) decreased and altered the gut microbiome composition of TB patients. The bacterial genera Bacteroides and Prevotella were significantly increased, and Blautia and Bifidobacterium decreased in the TB patients group. The fungi genus Saccharomyces was increased while decreased levels of Aspergillus in TB patients. It indicates that gut microbial equilibrium between bacteria and fungi has been altered in TB patients. The fungal-to-bacterial species ratio was significantly decreased, and the bacterial-fungal trans-kingdom interactions have been reduced in TB patients. A set model including Bacteroides, Blautia, Eubacterium_hallii_group, Apiotrichum, Penicillium, and Saccharomyces may provide a better TB diagnostics option than using single bacterial or fungi sets. Also, gut microbial dysbiosis has a strong correlation with the alteration of IL-17 and IFN-γ. CONCLUSIONS: Our results demonstrate that TB patients exhibit the gut bacterial and fungal dysbiosis. In the clinics, some gut microbes may be considered as potential biomarkers for auxiliary TB diagnosis.

Identification of metabolism-related key genes as potential biomarkers for pathogenesis of immune thrombocytopenia.

Immune thrombocytopenia (ITP), an acquired autoimmune disease, is characterized by immune-mediated platelet destruction. A biomarker is a biological entity that contributes to disease pathogenesis and reflects disease activity. Metabolic alterations are reported to be associated with the occurrence of various diseases. As metabolic biomarkers for ITP have not been identified. This study aimed to identify metabolism-related differentially expressed genes as potential biomarkers for pathogenesis of ITP using bioinformatic analyses.The microarray expression data of the peripheral blood mononuclear cells were downloaded from the Gene Expression Omnibus database (GSE112278 download link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112278 ). Key module genes were intersected with metabolism-related genes to obtain the metabolism-related key candidate genes. The hub genes were screened based on the degree function in the coytoscape sofware. The key ITP-related genes were subjected to functional enrichment analysis. Immune infiltration analysis was performed using a single-sample gene set enrichment analysis algorithm to evaluate the differential infiltration levels of immune cell types between ITP patient and control. Molecular subtypes were identified based on the expression of hub genes. The expression of hub genes in the ITP patients was validated using quantitative real-time polymerase chain reaction analysis. This study identified five hub genes (ADH4, CYP7A1, CYP1A2, CYP8B1, and NR1H4), which were be associated with the pathogenesis of ITP, and two molecular subtypes of ITP. Among these hub genes, CYP7A1 and CYP8B1 involved in cholesterol metabolism,were further verified in clinical samples.