Amino Acid-Induced Chemotaxis Plays a Key Role in the Adaptation of Vibrio harveyi from Seawater to the Muscle of the Host Fish.

Vibrio harveyi is a normal flora in natural marine habitats and a significant opportunistic pathogen in marine animals. This bacterium can cause a series of lesions after infecting marine animals, in which muscle necrosis and ulcers are the most common symptoms. This study explored the adaptation mechanisms of V. harveyi from the seawater environment to host fish muscle environment. The comprehensive transcriptome analysis revealed dramatic changes in the transcriptome of V. harveyi during its adaptation to the host fish muscle environment. Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, flagellar assembly, oxidative phosphorylation, bacterial chemotaxis, and two-component systems play crucial roles in V. harveyi's adaptation to host fish muscle. A comparison of biological phenotypes revealed that V. harveyi displayed a significant increase in flagellar length, swimming, twitching, chemotaxis, adhesion, and biofilm formation after induction by host fish muscle, and its dominant amino acids, especially bacterial chemotaxis induced by host muscle, Ala and Arg. It could be speculated that the enhancement of bacterial chemotaxis induced by amino acids plays a key role in the adaptation of V. harveyi from seawater to the muscle of the host fish.

Investigating the antiviral activity of Erigeron annuus (L.) pers extract against RSV and examining its active components.

ETHNOPHARMACOLOGICAL RELEVANCE: The plants in the genus Erigeron are known to exhibit antiviral activities, including those against the respiratory syncytial virus (RSV). In traditional medicine Erigeron annuus (L.) Pers (EA) has been used in the treatment of pulmonary diseases and acute infectious hepatitis. AIM OF THIS STUDY: The aim of this study is to determine the optimum extraction method to produce the most potent anti-RSV extract, elucidate its mode and mechanisms of antiviral activity in both in vitro and in vivo models, and identify the chemical structures of the bioactive compounds. MATERIALS AND METHODS: The whole plant of EA was extracted with ethyl acetate, methanol, ethanol, water, aqueous methanol (60, 80% and 100%) and aqueous ethanol (50, 75% and 95%) using maceration, reflux, and ultrasound-assisted extraction methods. The antiviral activities of the extracts were determined in vitro. The in vitro antiviral activities of the extracts were determined using Hep-2 cells. Four in vitro experiments were performed to determine the mode of antiviral activity of the most active extract, ethyl acetate fraction (EAE) of Erigeron annuus whole plant extract prepared by refluxing with 50% ethanol, by examining its ability to inactivate the virus directly, inhibit viral adsorption and penetration, inhibit viral replication and preventive effect. The effect of temperature and duration of treatment on these modes of action was also determined. The antiviral activity of the EAE was also assessed in vivo in a mouse model. The lung index, viral load, and lung tissue histology were measured. qRT-PCR and ELISA studies were performed to determine the expression of key genes (TLR-3 and TLR-4) and proteins (IL-2, IFN-γ, and TNF-α) related to RSV infection. The most active antiviral compound was isolated using chromatography techniques, and its chemical structure was identified through electrospray triple quadrupole mass spectroscopy and nuclear magnetic resonance spectroscopy. RESULTS: The EAE was the most active on RSV. In vitro experiments showed that the antiviral activity of EAE is via direct inactivation, inhibition of entry, and inhibition of the proliferation of the virus. In vivo experiments showed that the EAE effectively inhibited the proliferation of RSV in the lungs and alleviated the lung tissue lesions in RSV-infected mice. The antiviral activity of the EAE is mediated by downregulating the expression of TLR3 and TLR4 in the lung, upregulating the expression of IL-2 and IFN-γ, and downregulating the expression of TNF-α. Apigenin 7-O-methylglucuronide was found to be a major bioactive compound in EAE. CONCLUSIONS: The results of this study confirmed the antiviral activity of EA by inactivating, inhibiting the entry, and inhibiting the proliferation of RSV. The activity is mediated by regulating the immunity and inflammatory mediators. Apigenin 7-O-methylglucuronide is the bioactive compound present in EA.

Spontaneous aggregation-enhanced electrochemiluminescence via galvanic strategy.

Researchers unremittingly strive to develop innovative luminophores to enhance intrinsic electrochemiluminescence (ECL) performance. However, the potential to harness facile strategies, such as manipulating the physical properties of luminophores while retaining functional chemical properties to fabricate cost-effective ECL complexes, remains underexplored. Herein, we reported a novel and efficient one-step galvanic technique to actualize aggregation-enhanced ECL (AEECL) of ruthenium complexes. It marked the first instance of the galvanic process being employed to synthesize aggregate luminophores through electrostatic attraction. The ECL intensity and efficiency of the prepared ruthenium complexes with AEECL properties surpassed traditional ruthenium complexes by 8.9 and 13.6 times, respectively, outperforming most reported luminophores. Remarkably, the target luminophore exhibited high stability across varied scan rates and temperatures. Furthermore, a binder-free and carbon paper-based AEECL analytical device for lidocaine detection was fabricated, achieving a satisfactory detection limit (0.34 nM) and selectivity. The convenient modulation strategy of aggregate structure, along with the transformative leap from insufficient ECL to AEECL, bring forth a new revenue in aggregate science. This research also promises a universally applicable and versatile protocol for future biological analysis and bioimaging applications.

Tracheobronchial Foreign Body in Children with an Insidious Medical History.

This study explored the clinical features of tracheobronchial foreign bodies (TFB) in children lacking both a foreign body aspiration history and bronchial cut-off signs on imaging. This study was conducted between 2011 and 2021, including 45 children without a choking history or tracheal interruption on CT scans. Common symptoms were cough and wheezing (91.1%, 41 cases), followed by decreased breath sounds (55.6%, 25 cases), rales (48.9%, 22 cases), and wheezing (42.2%, 19 cases). Prior to TFB confirmation, bronchopneumonia was the prevalent diagnosis (88.9%, 40 cases). Vegetable matter was the most frequent foreign body type (75.6%, 34 cases), primarily located in the right main bronchus (31.1%) and left lower lobe bronchus (22.2%). TFB in children with obscure medical histories presents non-specifically, highlighting bronchoscopy's pivotal role in diagnosis and treatment. Key Words: Bronchoscope, Paediatrics, Tracheobronchial foreign body, Diagnosis.

An "off-on-enhanced on" electrochemiluminescence biosensor based on resonance energy transfer and surface plasmon coupled 3D DNA walker for ultra-sensitive detection of microRNA-21.

In this study, a novel electrochemiluminescence (ECL) biosensor was developed to detect microRNA-21 (miRNA-21) with high sensitivity by leveraging the combined mechanisms of resonance energy transfer (RET) and surface plasmon coupling (SPC). Initially, the glassy carbon electrode (GCE) were coated with Cu-Zn-In-S quantum dots (CZIS QDs), known for their defect-related emission suitable for ECL sensing. Subsequently, a hairpin DNA H3 with gold nanoparticles (Au NPs) attached at the end was modified over the surface of the quantum dots. The Au NPs could effectively quench the ECL signals of CZIS QDs via RET. Further, a significant amount of report DNA was generated through the action of a 3D DNA walker. When the report DNA opened H3-Au NPs, the hairpin structure experienced a conformational change to a linear shape, increasing the gap between the CZIS QDs and the Au NPs. Consequently, the localized surface plasmon resonance ECL (LSPR-ECL) effect replaced ECL resonance energy transfer (ECL-RET). Moreover, the report DNA was released following the addition of H4-Au NPs, resulting in the formation of Au dimers and a surface plasma-coupled ECL (SPC-ECL) effect that enhanced the ECL intensity to 6.97-fold. The integration of new ECL-RET and SPC-ECL biosensor accurately quantified miRNA-21 concentrations from 10-8 M to 10-16 M with a limit of detection (LOD) of 0.08 fM, as well as successfully applied to validate human serum samples.

Elucidating thoracic aortic dissection pathogenesis: The interplay of m1A-related gene expressions and miR-16-5p/YTHDC1 Axis in NLRP3-dependent pyroptosis.

The underlying molecular mechanisms of thoracic aortic dissection (TAD) remain incompletely understood. Recent insights into RNA methylation and microRNA-mediated gene regulation offer new avenues for exploring how these processes contribute to the pathophysiology of TAD, particularly through the modulation of pyroptosis and smooth muscle cell viability. This research aimed to elucidate the interplay of m1A-related gene expressions and miR-16-5p/YTHDC1 Axis in NLRP3-dependent pyroptosis, a mechanism implicated in the pathogenesis of TAD. We collected tissue samples from 28 human TAD patients and 8 healthy aortic group, as well as utilized a mouse model to replicate the disease. A combination of computational, in vitro, and in vivo methods was applied, including CIBERSORTx analysis, Pearson correlation, gene transfection using antagomiR-16-5p, siRNA, and several staining as well as cell culture techniques. Our analysis indicated two differentially expressed genes, ALKBH2 and YTHDC1. We found significant upregulation of has-miR-16-5p and downregulation of YTHDC1 at mRNA level in AD samples. Immune cell infiltration in TAD samples was examined using the CIBERSORTx database. We confirmed that YTHDC1 was a target of miR-16-5p, as evidenced by an inhibitory effect on luciferase activity. Inhibition of miR-16-5p enhanced SMC proliferation and promoted cell viability whilst downregulating NLRP3-pyroptosis. YTHDC1 expression was increased, and NLRP3-pyroptosis expressions were inhibited, suggesting miR-16-5p/YTHDC1 axis may involve the NLRP3-pyroptosis of the SMC. In vivo analyses confirmed the prevention of NLRP3-pyroptosis in middle layer of the thoracic aorta, implying that the miR-16-5p/YTHDC1 axis regulated SMC proliferation via NLRP3-pyroptosis signaling. Our findings underscored the anti-pyroptotic role of miR-16-5p/YTHDC1 axis in the pathogenesis of TAD, suggesting a potential therapeutic strategy via targeting YTHDC1 and suppressing miR-16-5p to inhibit NLRP3-dependent pyroptosis. Although further investigation is needed, these results relating to SMC proliferation are a significant step forward in understanding TAD.

Modular Synthesis of Polysubstituted α-Phosphorylated Arenes via the Catellani Strategy.

In this paper, we described a palladium/norbornene-catalyzed ortho-C-H phosphormethylation of aryl iodides using XCH2P(O)RR', offering a reliable method for the modular synthesis of polysubstituted α-phosphorylated arenes. Alkenylation, hydrogenation, cyanation, methylation, and arylation were all viable termination steps compatible with the reaction. This method demonstrates excellent functional group tolerance and can be extended to the late-stage modification of bioactive molecules. Furthermore, the synthetic transformations of the products demonstrate the practical utility of this reaction.

Oxygen Vacancy Mediation in SnO2 Electron Transport Layers Enables Efficient, Stable, and Scalable Perovskite Solar Cells.

Previous findings have suggested a close association between oxygen vacancies in SnO2 and charge carrier recombination as well as perovskite decomposition at the perovskite/SnO2 interface. Underlying the fundamental mechanism holds great significance in achieving a more favorable balance between the efficiency and stability. In this study, we prepared three SnO2 samples with different oxygen vacancy concentrations and observed that a low oxygen vacancy concentration is conducive to long-term device stability. Iodide ions were observed to easily diffuse into regions with high oxygen vacancies, thereby speeding up the deprotonation of FAI, as made evident by the detection of the decomposition product formamide. In contrast, a high oxygen vacancy concentration in SnO2 could prevent hole injection, leading to a decrease in interfacial recombination losses. To suppress this decomposition reaction and address the trade-off, we designed a bilayer SnO2 structure to ensure highly efficient carrier transport still while maintaining a chemically inert surface. As a result, an enhanced efficiency of 25.06% (certified at 24.55% with an active area of 0.09 cm2 under fast scan) was achieved, and the extended operational stability maintained 90% of their original efficiency (24.52%) after continuous operation for nearly 2000 h. Additionally, perovskite submodules with an active area of 14 cm2 were successfully assembled with a PCE of up to 22.96% (20.09% with an aperture area).

An Ultra-Conductive and Patternable 40 nm-Thick Polymer Film for Reliable Emotion Recognition.

Understanding psychology is an important task in modern society which helps predict human behavior and provide feedback accordingly. Monitoring of weak psychological and emotional changes requires bioelectronic devices to be stretchable and compliant for unobtrusive and high-fidelity signal acquisition. Thin conductive polymer film is regarded as an ideal interface; however, it is very challenging to simultaneously balance mechanical robustness and opto-electrical property. Here, a 40 nm-thick film based on photolithographic double-network conductive polymer mediated by graphene layer is reported, which concurrently enables stretchability, conductivity, and conformability. Photolithographic polymer and graphene endow the film photopatternability, enhance stress dissipation capability, as well as improve opto-electrical conductivity (4458 S cm-1@>90% transparency) through molecular rearrangement by π-π interaction, electrostatic interaction, and hydrogen bonding. The film is further applied onto corrugated facial skin, the subtle electromyogram is monitored, and machine learning algorithm is performed to understand complex emotions, indicating the outstanding ability for stretchable and compliant bioelectronics.

Archaeal communities change responding to anthropogenic and natural treatments of freeze-thawed soils.

The coverage of accumulated snow plays a significant role in inducing changes in both microbial activity and environmental factors within freeze-thaw soil systems. This study aimed to analyze the impact of snow cover on the dynamics of archeal communities in freeze-thaw soil. Furthermore, it seeks to investigate the role of fertilization in freeze-thaw soil. Four treatments were established based on snow cover and fertilization:No snow and no fertilizer (CK-N), snow cover without fertilizer (X-N), fertilizer without snow cover (T-N), and both fertilizer and snow cover (T-X). The research findings indicated that after snow cover treatment, the carbon, nitrogen, and phosphorus content in freeze-thaw soil exhibit periodic fluctuations. Snow covered effectively altered the community composition of bacteria and archaea in the soil, with a greater impact on archaeal communities than on bacterial communities. Snow covered improves the stability of archaeal communities in freeze-thaw soil. Additionally, the arrival of snow also enhanced the correlation between archaea and environmental factors, with the key archaeal phyla involved being Nanoarchaeota and Crenarchaeota. Further research showed that the application of organic fertilizers also had some impact on freeze-thaw soil, but this impact was smaller compared to snow cover. In summary, the arrival of snow could alter the archaeal community and protect nutrient elements in freeze-thaw soil, reducing their loss, and its effect is more pronounced compared to the application of organic fertilizers.

Phage-Bacterial Interaction Alters Phenotypes Associated with Virulence in Acinetobacter baumannii.

Bacteriophages exert strong selection on their bacterial hosts to evolve resistance. At the same time, the fitness costs on bacteria following phage resistance may change their virulence, which may affect the therapeutic outcomes of phage therapy. In this study, we set out to assess the costs of phage resistance on the in vitro virulence of priority 1 nosocomial pathogenic bacterium, Acinetobacter baumannii. By subjecting phage-resistant variant Ev5-WHG of A. baumannii WHG40004 to several in vitro virulence profiles, we found that its resistance to phage is associated with reduced fitness in host microenvironments. Also, the mutant exhibited impaired adhesion and invasion to mammalian cells, as well as increased susceptibility to macrophage phagocytosis. Furthermore, the whole-genome sequencing of the mutant revealed that there exist multiple mutations which may play a role in phage resistance and altered virulence. Altogether, this study demonstrates that resistance to phage can significantly alter phenotypes associated with virulence in Acinetobacter baumannii.

Study on the Efficacy and Clinical Value of Aminophylline and Doxofylline in the Clinical Treatment of Chronic Obstructive Pulmonary Disease.

Objective: To study and compare the efficacy and clinical value of aminophylline and doxofylline in the clinical treatment of chronic obstructive pulmonary disease (COPD). Method: The study analyzed the clinical data of 92 patients with chronic obstructive pulmonary disease who received either aminophylline or doxofylline treatment in the hospital from January 2020 to June 2022. The patients were divided into a control group composed of 46 COPD patients who received aminophylline treatment and a study group composed of 46 COPD patients who received doxofylline treatment. The two groups' total effective rate and incidence of adverse reactions were compared. The serum inflammatory factor indicators, symptom scores, pulmonary ventilation function, arterial blood gas, chest and lung responsiveness, sleep status indicators, and quality of life scores of the two groups before and after treatment were compared. Results: At the end of treatment, the total effective rate was higher in the study group compared to the control group (P < .05). Regarding adverse reactions, the study group's total incidence was lower than the control group's (P < .05). After treatment, the levels of serum inflammatory factor indicators of CRP, PCT, and TNF- α in both groups were decreased compared with those before treatment; while comparing the above indicators between the groups, it was found that the values in the study group were lower (all P < .05). After treatment, the scores of symptoms such as cough, expectoration, and shortness of breath in both groups of patients were significantly lower than before treatment, while compared to the control group, the scores of all symptoms were lower in the study group (P < .05). After treatment, compared with FEV1, FEV1/FVC, PaO2, and PaCO2 before treatment, the above indicators in both groups were significantly improved. However, compared with various indicators in the control group, the values of FEV1, FEV1/FVC, and PaO2 in the study group were higher, while the values of PaCO2 in the study group were lower (all P < .05). After treatment, the measured values of indicators such as thoracic compliance, lung compliance, and total compliance in the two groups were significantly higher compared with those before the treatment, while compared to the control group, the values of all indicators in the study group were higher (P < .05). After treatment, compared with the control group's monitoring of various indicators of nighttime sleep, the study group obtained better data on monitoring of sleep latency and actual sleep duration. The group obtained lower scores in sleep quality evaluation, while the two groups significantly improved their sleep-related data in night-time monitoring and evaluation compared to those before treatment, with all P < .05. After treatment, the scores in various aspects of the quality of life of patients in both groups were significantly increased compared to those before treatment, and after comparing the scores of various quality of life between the two groups, it was found that the study group was higher than the control group (all P < .05). Conclusion: After the onset of COPD, doxofylline treatment can achieve better effects than aminophylline treatment.

[Correlation between CRAB Symptoms and Antioxidant Enzyme Activity in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the relationship between clinical indicators of CRAB symptoms and antioxidant enzyme activity in patients with multiple myeloma (MM). METHODS: The activity of catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in the bone marrow supernatants of 44 patients with MM and 12 patients with non-malignant hematological diseases was detected by colorimetric assay, and then the differences in the activity of antioxidant enzymes between the two groups were compared. Furthermore, the relationship between the activity of antioxidant enzymes in the MM group and the levels of serum calcium, serum creatinine (Scr), hemoglobin (Hb), alkaline phosphatase (ALP) as well as bone lesions were analyzed. RESULTS: The antioxidant enzyme activity was lower in MM patients compared with the control group (P < 0.05). When the concentrations of serum calcium and ALP were higher than the normal levels, Hb was lower than 85 g/L, and there were multiple bone lesions, the activity of CAT, SOD and GPX was significantly declined (P < 0.05); When the concentration of Scr≥177 µmol/L, the activity of GPX was significantly declined (P < 0.05). Regression analyses showed that CAT, SOD and GPX were negatively correlated with serum calcium (r =-0.538, r =-0.456, r =-0.431), Scr (r =-0.342, r =-0.384, r =-0.463), and ALP (r =-0.551, r =-0.572, r =-0.482). CONCLUSION: The activity of antioxidant enzymes, including CAT, SOD and GPX, were decreased in patients with MM and they were negatively correlated with some clinical indicators of CRAB symptoms (such as serum calcium, Scr, and ALP), which suggests that promoting the activity of antioxidant enzymes may be beneficial to treat the CRAB symptoms of the patients with MM.

Butyrate alleviates alcoholic liver disease-associated inflammation through macrophage regulation and polarization via the HDAC1/miR-155 axis.

BACKGROUND: We recently found that butyrate could ameliorate inflammation of alcoholic liver disease (ALD) in mice. However, the exact mechanism remains incompletely comprehended. Here, we examined the role of butyrate on ALD-associated inflammation through macrophage (Mψ) regulation and polarization using in vivo and in vitro experiments. METHODS: For in vivo experiments, C57BL/6J mice were fed modified Lieber-DeCarli liquid diets supplemented with or without ethanol and sodium butyrate (NaB). After 6 weeks of treatment, mice were euthanized and associated indicators were analyzed. For in vitro experiments, lipopolysaccharide (LPS)-induced inflammatory murine RAW264.7 cells were treated with NaB or miR-155 inhibitor/mimic to verify the anti-inflammatory effect and underlying mechanism. RESULTS: The administration of NaB alleviated pathological damage and associated inflammation, including LPS, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß levels in ALD mice. NaB intervention restored the imbalance of macrophage polarization by inhibiting inducible nitric oxide synthase (iNOS) and elevating arginase-1 (Arg-1). Moreover, NaB reduced histone deacetylase-1 (HDAC1), nuclear factor kappa-B (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and miR-155 expression in ALD mice, but also increased peroxisome proliferator-activated receptor-γ (PPAR-γ). Thus, MiR-155 was identified as a strong regulator of ALD. To further penetrate the role of miR-155, LPS-stimulated RAW264.7 cells co-cultured with NaB were treated with the specific inhibitor or mimic. Intriguingly, miR-155 was capable of negatively regulated inflammation with NaB intervention by targeting SOCS1, SHIP1, and IRAK-M genes. CONCLUSION: Butyrate suppresses the inflammation in mice with ALD by regulating macrophage polarization via the HDAC1/miR-155 axis, which may potentially contribute to the novel therapeutic treatment for the disease.

Rapid and Mechanically Robust Immobilization of Proteins on Silica Studied at the Single-Molecule Level by Force Spectroscopy and Verified at the Macroscopic Level.

Typical methods for stable immobilization of proteins often involve time-consuming surface modification of silicon-based materials to enable specific binding, while the nonspecific adsorption method is faster but usually unstable. Herein, we fused a silica-binding protein, Si-tag, to target proteins so that the target proteins could attach directly to silica substrates in a single step, markedly streamlining the immobilization process. The adhesion force between the Si-tag and glass substrates was determined to be approximately 400-600 pN at the single-molecule level by atomic force microscopy, which is greater than the unfolding force of most proteins. The adhesion force of the Si-tag exhibits a slight increase when pulled from the C-terminus compared to that from the N-terminus. Furthermore, the Si-tag's adhesion force on a glass surface is marginally higher than that on a silicon nitride probe. The binding properties of the Si-tag are not obviously affected by environmental factors, including pH, salt concentration, and temperature. In addition, the macroscopic adhesion force between the Si-tag-coated hydrogel and glass substrates was ∼40 times higher than that of unmodified hydrogels. Therefore, the Si-tag, with its strong silica substrate binding ability, provides a useful tool as an excellent fusion tag for the rapid and mechanically robust immobilization of proteins on silica and for the surface coating of silica-binding materials.

Clostridium butyricum inhibits the inflammation in children with primary nephrotic syndrome by regulating Th17/Tregs balance via gut-kidney axis.

BACKGROUND: Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Clostridium butyricum (C. butyricum), a probiotic producing butyric acid, exerts effective in regulating inflammation. This study was designed to elucidate the effect of C. butyricum on PNS inflammation through the gut-kidney axis. METHOD: BALB/c mice were randomly divided into 4 groups: normal control group (CON), C. butyricum control group (CON+C. butyricum), PNS model group (PNS), and PNS with C. butyricum group (PNS+C. butyricum). The PNS model was established by a single injection of doxorubicin hydrochloride (DOX) through the tail vein. After 1 week of modeling, the mice were treated with C. butyricum for 6 weeks. At the end of the experiment, the mice were euthanized and associated indications were investigated. RESULTS: Since the successful modeling of the PNS, the 24 h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), urine urea nitrogen (UUN), urine creatinine (UCr), lipopolysaccharides (LPS), pro-inflammatory interleukin (IL)-6, IL-17A were increased, the kidney pathological damage was aggravated, while a reduction of body weights of the mice and the anti-inflammatory IL-10 significantly reduced. However, these abnormalities could be dramatically reversed by C. butyricum treatment. The crucial Th17/Tregs axis in PNS inflammation also was proved to be effectively regulated by C. butyricum treatment. This probiotic intervention notably affected the expression levels of signal transducer and activator of transcription 3 (STAT3), Heme oxygenase-1 (HO-1) protein, and retinoic acid-related orphan receptor gamma t (RORγt). 16S rRNA sequencing showed that C. butyricum could regulate the composition of the intestinal microbial community and found Proteobacteria was more abundant in urine microorganisms in mice with PNS. Short-chain fatty acids (SCFAs) were measured and showed that C. butyricum treatment increased the contents of acetic acid, propionic acid, butyric acid in feces, acetic acid, and valeric acid in urine. Correlation analysis showed that there was a closely complicated correlation among inflammatory indicators, metabolic indicators, microbiota, and associated metabolic SCFAs in the gut-kidney axis. CONCLUSION: C. butyricum regulates Th17/Tregs balance via the gut-kidney axis to suppress the immune inflammatory response in mice with PNS, which may potentially contribute to a safe and inexpensive therapeutic agent for PNS.

Knocking Down HN1 Blocks Helicobacter pylori-Induced Malignant Phenotypes in Gastric Mucosal Cells and Inhibits Gastric Cancer Cell Proliferation, Cytoskeleton Remodeling, and Migration.

Helicobacter pylori (H. pylori) is implicated in the aberrant proliferation and malignant transformation of gastric mucosal cells, heightening the risk of gastric cancer (GC). HN1 is involved in the development of various tumors. However, precise mechanistic underpinnings of HN1 promoting GC progression in H. pylori remain elusive. The study collected 79 tissue samples of GC patients, including 47 with H. pylori-positive GC and 32 H. pylori-negative controls. Using human gastric epithelial cells (GES-1) and human gastric adenocarcinoma cells (HGC-27), the effect of overexpression / knocking down of HN1 and H. pylori infection was evaluated on cell function (proliferation, migration, apoptosis), cytoskeleton, and expression of cell malignant phenotype factors that promote the malignant biological behavior of cancer cells. The expression of HN1 in GC tissues is higher than that in paracancerous tissue and is closely related to infiltration, lymphatic metastasis, distant metastasis, survival, and H. pylori infection. Downregulation of HN1 effectively hinders the ability of H. pylori strains 26695 and SS1 to promote migration of GES-1 and HGC-27 cells, while lowering the expression of key indicators associated with malignant phenotype. Downregulated GSK3B, ß-catenin, and Vimentin after knockdown Integrinß1, but HN1 expression remained largely unchanged, when HN1 and Integrinß1 were knocked down, GSK3B, ß-catenin, and Vimentin expression were considerably reduced. Our research demonstrated the crucial role of HN1 in H. pylori-induced acquisition of a malignant phenotype in GES-1 cells. Knockdown of HN1 blocked the pathogenic mechanism of H. pylori-induced GC and downregulated the expression of GSK3Β, ß-catenin and Vimentin via Integrin ß1.

Effects of Bifidobacterium animalis subsp. lactis IU100 on Immunomodulation and Gut Microbiota in Immunosuppressed Mice.

Probiotics are live microorganisms with immunomodulatory effects in a strain-specific and dose-dependent manner. Bifidobacterium animalis subsp. lactis IU100 is a new probiotic strain isolated from healthy adults. This study aimed to evaluate the effects of IU100 on cyclophosphamide (CTX)-induced immunosuppression in mice. The results showed that IU100 significantly ameliorated CTX-induced decreases in body weight and immune organ indices. The promoted delayed-type hypersensitivity, serum hemolysins and immunoglobulin (IgA, IgG and IgM) levels after IU100 treatment indicated its enhancing role in cellular and humoral immunity. In addition, oral administration of IU100 increased serum cytokine (IL-1ß, IL-2, IL-4, IL-6, IFN-γ, TNF-α) levels dose-dependently, which are associated with CTX-induced shifts in the Th1/Th2 balance. The probiotic IU100 also modulated the composition of gut microbiota by reducing the Firmicutes/Bacteroidetes ratio; increasing beneficial Muribaculaceae and the Lachnospiraceae NK4A136 group; and inhibiting harmful Clostridium sensu stricto 1, Faecalibaculum and Staphylococcus at the genus level. The above genera were found to be correlated with serum cytokines and antibody levels. These findings suggest that IU100 effectively enhances the immune function of immunosuppressed mice, induced by CTX, by regulating gut microbiota.

Internal m 6 A and m 7 G RNA modifications in hematopoietic system and acute myeloid leukemia.

ABSTRACT: Epitranscriptomics focuses on the RNA-modification-mediated post-transcriptional regulation of gene expression. The past decade has witnessed tremendous progress in our understanding of the landscapes and biological functions of RNA modifications, as prompted by the emergence of potent analytical approaches. The hematopoietic system provides a lifelong supply of blood cells, and gene expression is tightly controlled during the differentiation of hematopoietic stem cells (HSCs). The dysregulation of gene expression during hematopoiesis may lead to severe disorders, including acute myeloid leukemia (AML). Emerging evidence supports the involvement of the mRNA modification system in normal hematopoiesis and AML pathogenesis, which has led to the development of small-molecule inhibitors that target N6-methyladenosine (m 6 A) modification machinery as treatments. Here, we summarize the latest findings and our most up-to-date information on the roles of m 6 A and N7-methylguanine in both physiological and pathological conditions in the hematopoietic system. Furthermore, we will discuss the therapeutic potential and limitations of cancer treatments targeting m 6 A.

PHDtools: A platform for pathogen detection and multi-dimensional genetic signatures decoding to realize pathogen genomics data analyses online.

OBJECTIVES: Facing the emerging diseases, rapid identification of the pathogen and multi-dimensional characterization of the genomic features at both isolate-level and population-level through high-throughput sequencing data can provide invaluable information to guide the development of antiviral agents and strategies. However, a user-friendly program is in urgent need for clinical laboratories without bioinformatics background to decode the complex big genomics data. METHODS: In this study, we developed an interactive online platform named PHDtools with a total of 15 functions to analyze metagenomics data to identify the potential pathogen and decode multi-dimensional genetic signatures including intra-/inter-host variations and lineage-level variations. The platform was applied to analyze the meta-genomic data of the samples collected from the 172 imported COVID-19 cases. RESULTS: According to the analytical results of mNGS, 27 patients were found to have the co-infections of SARS-CoV-2 with either influenza virus (n = 9) or human picobirnavirus (n = 19). Enough coverages of all the assembled SARS-CoV-2 genomes provided the sub-lineages of Omicron variant, and the number of mutations in the non-structural genes and M gene was increased, as well as the intra-host variations occurred in E and M gene were under positive selection (Ka/Ks > 1). These findings of increased or changed mutations in the SARS-CoV-2 genome characterized the current adaptive evolution patterns of Omicron sub-lineages, and revealed the evolution speed of these sub-lineages might increase. CONCLUSIONS: Consequently, the application of PHDtools has proved that this platform is accurate, user-friendly and convenient for clinical users who are deficient in bioinformatics, and the clinical monitor of SARS-CoV-2 genomes by PHDtools also highlighted the potential evolution features of current SARS-CoV-2 and indicated that the development of anti-SARS-CoV-2 agents and new-designed vaccines should incorporate the gene variations other than S gene.