Gel-confined fabrication of fully bio-based filtration membrane for green capture and rapid detection of airborne microbes.

Air filtration has become a desirable route for collecting airborne microbes. However, the potential biotoxicity and sterilization of current air filtration membranes often lead to undesired inactivation of captured microbes, which greatly limits microbial non-traumatic transfer and recovery. Herein, we report a gel-confined phase separation strategy to rationally fabricate a fully bio-based filtration membrane (SGFM) using soluble soybean polysaccharide and gelatin. The versatile SGFM features fascinating honeycomb micro-nano architecture and hierarchical interconnected porous structures for microbial capture, and achieves a lower pressure drop, higher interception efficiency (99.3%), and superior microbial survivability than commercial gelatin filtration membranes. Particularly, the water-dissolvable SGFM can greatly simplify the elution and extraction process after bioaerosol sampling, thereby bringing about maximum sample transfer and vigorous recovery of collected microbes. Meanwhile, green capture coupled with ATP bioluminescence endows the SGFM with rapid and quantitative detection capability for airborne microbes. This work may pave the way for designing green protocols for the detection of bioaerosols.

Correction: Innovative wound management: creating dynamic Alg-Mg/SF hydrogels for controlled Mg2+ release in wound healing.

[This corrects the article DOI: 10.1039/D4RA00793J.].

Molecular characterization and induced changes of histone acetyltransferases in the tick Haemaphysalis longicornis in response to cold stress.

BACKGROUND: Epigenetic modifications of histones play important roles in the response of eukaryotic organisms to environmental stress. However, many histone acetyltransferases (HATs), which are responsible for histone acetylation, and their roles in mediating the tick response to cold stress have yet to be identified. In the present study, HATs were molecularly characterized and their associations with the cold response of the tick Haemaphysalis longicornis explored. METHODS: HATs were characterized by using polymerase chain reaction (PCR) based on published genome sequences, followed by multiple bioinformatic analyses. The differential expression of genes in H. longicornis under different cold treatment conditions was evaluated using reverse transcription quantitative PCR (RT-qPCR). RNA interference was used to explore the association of HATs with the cold response of H. longicornis. RESULTS: Two HAT genes were identified in H. longicornis (Hl), a GCN5-related N-acetyltransferase (henceforth HlGNAT) and a type B histone acetyltransferase (henceforth HlHAT-B), which are respectively 960 base pairs (bp) and 1239 bp in length. Bioinformatics analysis revealed that HlGNAT and HlHAT-B are unstable hydrophilic proteins characterized by the presence of the acetyltransferase 16 domain and Hat1_N domain, respectively. RT-qPCR revealed that the expression of HlGNAT and HlHAT-B decreased after 3 days of cold treatment, but gradually increased with a longer period of cold treatment. The mortality rate following knockdown of HlGNAT or HlHAT-B by RNA interference, which was confirmed by RT-qPCR, significantly increased (P < 0.05) when H. longicornis was treated at the lowest lethal temperature (- 14 °C) for 2 h. CONCLUSIONS: The findings demonstrate that HATs may play a crucial role in the cold response of H. longicornis. Thus further research is warranted to explore the mechanisms underlying the epigenetic regulation of the cold response in ticks.

A non-canonical role of the inner kinetochore in regulating sister-chromatid cohesion at centromeres.

The 16-subunit Constitutive Centromere-associated Network (CCAN)-based inner kinetochore is well-known for connecting centromeric chromatin to the spindle-binding outer kinetochore. Here, we report a non-canonical role for the inner kinetochore in directly regulating sister-chromatid cohesion at centromeres. We provide biochemical, X-ray crystal structure, and intracellular ectopic localization evidence that the inner kinetochore directly binds cohesin, a ring-shaped multi-subunit complex that holds sister chromatids together from S-phase until anaphase onset. This interaction is mediated by binding of the 5-subunit CENP-OPQUR sub-complex of CCAN to the Scc1-SA2 sub-complex of cohesin. Mutation in the CENP-U subunit of the CENP-OPQUR complex that abolishes its binding to the composite interface between Scc1 and SA2 weakens centromeric cohesion, leading to premature separation of sister chromatids during delayed metaphase. We further show that CENP-U competes with the cohesin release factor Wapl for binding the interface of Scc1-SA2, and that the cohesion-protecting role for CENP-U can be bypassed by depleting Wapl. Taken together, this study reveals an inner kinetochore-bound pool of cohesin, which strengthens centromeric sister-chromatid cohesion to resist metaphase spindle pulling forces.

Effects of Narrative Exposure Therapy for Treating Depressive and Anxious Disorders: A Systematic Review and Meta-Analysis.

OBJECTIVE: Narrative exposure therapy (NET) has been used in various contexts for the treatment of the effects of trauma, with promising results in clinical trials. However, its effects on anxiety and depression are still unclear. The present study is a systematic review and meta-analysis of the effects of NET on depression and anxiety. METHODS: The Embase, Cumulative Index of Nursing and Allied Health Literature, PubMed, Web of Science core collection, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, and Wangfang databases were searched from the earliest records to March 2023. Two researchers independently screened the literature, extracted data, evaluated the risk of bias, and cross-checked the data. Meta-analysis was performed using the program RevMan 5.3. RESULTS: Eleven randomized controlled trials with a total of 754 participants were included in the study. The results showed that NET reduced both the depression (standard mean difference [SMD]=-0.51, 95% confidence interval [CI] -0.73--0.29, p<0.00001) and anxiety (SMD=-0.65, 95% CI -1.13--0.18, p=0.007) scores of the patients. Furthermore, NET was found to alleviate negative emotions associated with guilt (mean difference [MD]=-3.60, 95% CI -5.52--1.68, p=0.0005) and negative change (MD=-5.80, 95% CI -9.76--1.83, p=0.004). CONCLUSION: This analysis showed that NET can alleviate depression and anxiety. It may thus be used in clinical settings to alleviate patients' negative feelings and aid their overall recovery.

Photoacoustic Imaging-Guided Self-Adaptive Hyperthermia Supramolecular Cascade Nano-Reactor for Diabetic Periodontal Bone Regeneration.

Commencing with the breakdown of the diabetic osteoimmune microenvironment, multiple pathogenic factors, including hyperglycemia, inflammation, hypoxia, and deleterious cytokines, are conjointly involved in the progression of diabetic periodontal bone regeneration. Based on the challenge of periodontal bone regeneration treatment and the absence of real-time feedback of blood oxygen fluctuation in diabetes mellitus, a novel self-adaptive hyperthermia supramolecular cascade nano-reactor ACFDG is constructed via one-step supramolecular self-assembly strategy to address multiple factors in diabetic periodontal bone regeneration. Hyperthermia supramolecular ACFDG possesses high photothermal conversion efficiency (32.1%), and it can effectively inhibit the vicious cycle of ROS-inflammatory cascade through catalytic cascade reactions, up-regulate the expression of heat shock proteins (HSPs) under near-infrared (NIR) irradiation, which promotes periodontal bone regeneration. Remarkably, ACFDG can provide real-time non-invasive diagnosis of blood oxygen changes during periodontal bone regeneration through photoacoustic (PA) imaging, thus can timely monitor periodontal hypoxia status. In conclusion, this multifunctional supramolecular nano-reactor combined with PA imaging for real-time efficacy monitoring provides important insights into the biological mechanisms of diabetic periodontal bone regeneration and potential clinical theranostics.

Dissecting causal relationships between primary biliary cholangitis and extrahepatic autoimmune diseases based on Mendelian randomization.

As an autoimmune disease, up to 73% of patients with primary biliary cholangitis (PBC) have a combination of extrahepatic autoimmune diseases (EHAIDs); however, the causal relationship between PBC and EHAIDs is unclear. The genome-wide association analyses provided 14 GWAS data for PBC and EHAIDs, and bidirectional, two-sample MR analyses were performed to examine the relationship between PBC and EHAIDs. The analysis using MR provides a strong and meaningful estimation of the bidirectional correlation between PBC and 7 EHAIDs: rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, autoimmune hypothyroidism, inflammatory bowel disease and ulcerative colitis of its types. In addition, PBC increases the risk of autoimmune thyroid diseases such as autoimmune hyperthyroidism and Graves' disease, as well as multiple sclerosis and psoriasis. Additionally, PBC is identified as a risk factor for Crohn's disease and Celiac disease. Based on genetic evidence, there may be connections between PBC and specific EHAIDs: not all coexisting EHAIDs induce PBC, and vice versa. This underscores the significance of prioritizing PBC in clinical practice. Additionally, if any liver function abnormalities are observed during treatment or with EHAIDs, it is crucial to consider the possibility of comorbid PBC.

Diagnostic implications of ubiquitination-related gene signatures in Alzheimer's disease.

The purpose of this study was to explore the diagnostic implications of ubiquitination-related gene signatures in Alzheimer's disease. In this study, we first collected 161 samples from the GEO database (including 87 in the AD group and 74 in the normal group). Subsequently, through differential expression analysis and the iUUCD 2.0 database, we obtained 3450 Differentially Expressed Genes (DEGs) and 806 Ubiquitin-related genes (UbRGs). After taking the intersection, we obtained 128 UbR-DEGs. Secondly, by conducting GO and KEGG enrichment analysis on these 128 UbR-DEGs, we identified the main molecular functions and biological pathways related to AD. Furthermore, through the utilization of GSEA analysis, we have gained insight into the enrichment of functions and pathways within both the AD and normal groups. Further, using lasso regression analysis and cross-validation techniques, we identified 22 characteristic genes associated with AD. Subsequently, we constructed a logistic regression model and optimized it, resulting in the identification of 6 RUbR-DEGs: KLHL21, WDR82, DTX3L, UBTD2, CISH, and ATXN3L. In addition, the ROC result showed that the diagnostic model we built has excellent accuracy and reliability in identifying AD patients. Finally, we constructed a lncRNA-miRNA-mRNA (competing endogenous RNA, ceRNA) regulatory network for AD based on six RUbR-DEGs, further elucidating the interaction between UbRGs and lncRNA, miRNA. In conclusion, our findings will contribute to further understanding of the molecular pathogenesis of AD and provide a new perspective for AD risk prediction, early diagnosis and targeted therapy in the population.

Optimization of tracheoesophageal fistula model established with T-shaped magnet system based on magnetic compression technique.

BACKGROUND: The magnetic compression technique has been used to establish an animal model of tracheoesophageal fistula (TEF), but the commonly shaped magnets present limitations of poor homogeneity of TEF and poor model control. We designed a T-shaped magnet system to overcome these problems and verified its effectiveness via animal experiments. AIM: To investigate the effectiveness of a T-shaped magnet system for establishing a TEF model in beagle dogs. METHODS: Twelve beagles were randomly assigned to groups in which magnets of the T-shaped scheme (study group, n = 6) or normal magnets (control group, n = 6) were implanted into the trachea and esophagus separately under gastroscopy. Operation time, operation success rate, and accidental injury were recorded. After operation, the presence and timing of cough and the time of magnet shedding were observed. Dogs in the control group were euthanized after X-ray and gastroscopy to confirm establishment of TEFs after coughing, and gross specimens of TEFs were obtained. Dogs in the study group were euthanized after X-ray and gastroscopy 2 wk after surgery, and gross specimens were obtained. Fistula size was measured in all animals, and then harvested fistula specimens were examined by hematoxylin and eosin (HE) and Masson trichrome staining. RESULTS: The operation success rate was 100% for both groups. Operation time did not differ between the study group (5.25 min ± 1.29 min) and the control group (4.75 min ± 1.70 min; P = 0.331). No bleeding, perforation, or unplanned magnet attraction occurred in any animal during the operation. In the early postoperative period, all dogs ate freely and were generally in good condition. Dogs in the control group had severe cough after drinking water at 6-9 d after surgery. X-ray indicated that the magnets had entered the stomach, and gastroscopy showed TEF formation. Gross specimens of TEFs from the control group showed the formation of fistulas with a diameter of 4.94 mm ± 1.29 mm (range, 3.52-6.56 mm). HE and Masson trichrome staining showed scar tissue formation and hierarchical structural disorder at the fistulas. Dogs in the study group did not exhibit obvious coughing after surgery. X-ray examination 2 wk after surgery indicated fixed magnet positioning, and gastroscopy showed no change in magnet positioning. The magnets were removed using a snare under endoscopy, and TEF was observed. Gross specimens showed well-formed fistulas with a diameter of 6.11 mm ± 0.16 mm (range, 5.92-6.36 mm), which exceeded that in the control group (P < 0.001). Scar formation was observed on the internal surface of fistulas by HE and Masson trichrome staining, and the structure was more regular than that in the control group. CONCLUSION: Use of the modified T-shaped magnet scheme is safe and feasible for establishing TEF and can achieve a more stable and uniform fistula size compared with ordinary magnets. Most importantly, this model offers better controllability, which improves the flexibility of follow-up studies.

Sirolimus is effective for refractory/relapsed idiopathic multicentric Castleman disease: A single-center, retrospective study.

Refractory/relapsed idiopathic multicentric Castleman disease (R/R iMCD) has limited treatment options. With studies showing increased mTOR activation in iMCD patients, sirolimus becomes an attractive and promising therapy for R/R iMCD. Here we report the results of a retrospective study involving 26 R/R iMCD patients treated with sirolimus-containing regimen. The median age at sirolimus initiation was 40.5 years (23-60), with a median prior treatment line of 2 (1-5). 18 patients (69.2%) achieved symptomatic and biochemical response, with a median time to at least overall partial remission of 1.9 months (0.5-14.6). The median follow-up time from sirolimus initiation was 11.7 months (1.6-50.7) and the median time to next treatment (TTNT) was 46.2 months. No patients died at the end of follow-up. Most of the patients in the cohort are in ongoing responses and continue sirolimus therapy. Sirolimus is well tolerated with minor adverse effects. In conclusion, sirolimus is effective for R/R iMCD patients with good tolerance.

Identification of potential key lipid metabolism-related genes involved in tubular injury in diabetic kidney disease by bioinformatics analysis.

AIMS: Accumulating evidences indicate that abnormalities in tubular lipid metabolism play a crucial role in the development of diabetic kidney disease (DKD). We aim to identify novel lipid metabolism-related genes associated with tubular injury in DKD by utilizing bioinformatics approaches. METHODS: Differentially expressed genes (DEGs) between control and DKD tubular tissue samples were screened from the Gene Expression Omnibus (GEO) database, and then were intersected with lipid metabolism-related genes. Hub genes were further determined by combined weighted gene correlation network analysis (WGCNA) and protein-protein interaction (PPI) network. We performed enrichment analysis, immune analysis, clustering analysis, and constructed networks between hub genes and miRNAs, transcription factors and small molecule drugs. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic efficacy of hub genes. We validated the relationships between hub genes and DKD with external datasets and our own clinical samples. RESULTS: There were 5 of 37 lipid metabolism-related DEGs identified as hub genes. Enrichment analysis demonstrated that lipid metabolism-related DEGs were enriched in pathways such as peroxisome proliferator-activated receptors (PPAR) signaling and pyruvate metabolism. Hub genes had potential regulatory relationships with a variety of miRNAs, transcription factors and small molecule drugs, and had high diagnostic efficacy. Immune infiltration analysis revealed that 13 immune cells were altered in DKD, and hub genes exhibited significant correlations with a variety of immune cells. Through clustering analysis, DKD patients could be classified into 3 immune subtypes and 2 lipid metabolism subtypes, respectively. The tubular expression of hub genes in DKD was further verified by other external datasets, and immunohistochemistry (IHC) staining showed that except ACACB, the other 4 hub genes (LPL, AHR, ME1 and ALOX5) exhibited the same results as the bioinformatics analysis. CONCLUSION: Our study identified several key lipid metabolism-related genes (LPL, AHR, ME1 and ALOX5) that might be involved in tubular injury in DKD, which provide new insights and perspectives for exploring the pathogenesis and potential therapeutic targets of DKD.

Introducing terminal alkyne groups at the reducing end of cellulose nanocrystals by aldimine condensation for further click reaction.

In recent years, click reactions with cellulose nanocrystals (CNC) participation have gradually become a research hotspot. Carboxylamine condensation is the most used method to introduce terminal alkyne groups at the reducing end of CNC as reaction sites for click reactions. However, hydroxyl groups on CNC surface would be slightly oxidized during the carboxyamine condensation process, inducing the potential positions of introduced alkynes would be not only at the reducing end but also on CNC surface. Here, aldimine condensation was proposed to introduce terminal alkyne groups just at the reducing end of CNC, and a systematic comparison analysis was conducted with carboxylamine condensation. Firstly, the selectivity and extent of alkynylation were characterized by XPS and EA. Secondly, the end aldehyde content in these CNC samples was measured by the BCA method, which quantitatively explained the grafting efficiency of aldimine condensation and further verified its feasibility. Thirdly, the clickability of the modified CNC samples was confirmed through XPS analysis of the products after a pre-designed click reaction. In sum, aldimine condensation was proven to be a simple and effective strategy for introducing terminal alkyne groups at the reducing end of CNC, which could be used as reaction sites for further click reactions.

Sulfated Chitosan-Modified CuS Nanocluster: A Versatile Nanoformulation for Simultaneous Antibacterial and Bone Regenerative Therapy in Periodontitis.

Periodontitis, a prevalent chronic inflammatory disease worldwide, is triggered by periodontopathogenic bacteria, resulting in the progressive destruction of periodontal tissue, particularly the alveolar bone. To effectively address periodontitis, this study proposed a nanoformulation known as CuS@MSN-SCS. This formulation involves coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSNs), followed by surface modification using amino groups and sulfated chitosan (SCS) through electrostatic interactions. The objective of this formulation is to achieve efficient bacteria removal by inducing ROS signaling pathways mediated by Cu2+ ions. Additionally, it aims to promote alveolar bone regeneration through Cu2+-induced pro-angiogenesis and SCS-mediated bone regeneration. As anticipated, by regulating the surface charges, the negatively charged CuS nanoparticles capped with sodium citrate were successfully coated with MSNs, and the subsequent introduction of amine groups using (3-aminopropyl)triethoxysilane was followed by the incorporation of SCS through electrostatic interactions, resulting in the formation of CuS@MSN-SCS. The developed nanoformulation was verified to not only significantly exacerbate the oxidative stress of Fusobacterium nucleatum, thereby suppressing bacteria growth and biofilm formation in vitro, but also effectively alleviate the inflammatory response and promote alveolar bone regeneration without evident biotoxicity in an in vivo rat periodontitis model. These findings contribute to the therapeutic effect on periodontitis. Overall, this study successfully developed a nanoformulation for combating bacteria and facilitating alveolar bone regeneration, demonstrating the promising potential for clinical treatment of periodontitis.

Synergistic Catalytic Performance of Pt-Au Bimetallic Catalysts on High-Crystallinity ZSM-23 Zeolite for Hexadecane Hydroisomerization: Metal-Acid Balance and Enhanced Isomerization Selectivity.

Highly crystalline ZSM-23 zeolite, exhibiting a distinctive dumbbell morphology, was synthesized via a hydrothermal method. Bifunctional catalysts, comprising single metals (Pt or Au) and bimetals (Pt-Au), were successfully prepared by using a positional precipitation method. The hydroisomerization of hexadecane served as a model reaction to assess the catalytic performance arising from the synergistic effects of bimetallic active sites. In comparison to single-metal catalysts, 0.3Au0.7Pt/ZSM-23 demonstrated increased n-C16 conversion, while 0.5Au0.5Pt/ZSM-23 exhibited enhanced i-C16 selectivity, achieving the highest i-C16 yield. The bimetallic catalyst not only finely tuned the metal site activity through bimetallic synergy but also achieved a superior balance between metal and acid catalysis, resulting in improved catalytic performance in the n-C16 hydroisomerization. The Pt-Au bimetallic catalyst approached the ideal requirements for a hydroisomerization catalyst, achieving a harmonious balance of metal and acid catalysis.

Clinical observation on treatment of Alzheimer's disease with Sun's scalp-abdominal acupuncture combined with donepezil hydrochloride. / å­™æ°å¤´é’ˆè ¹é’ˆè”åˆç›é ¸å¤šå¥ˆå“Œé½æ²»ç–—é˜¿å°”èŒ¨æµ·é»˜ç— çš„ä¸´åºŠè§‚å¯Ÿ.

OBJECTIVES: To observe the effect of scalp-abdominal acupuncture combined with donepezil hydrochloride on cognition and life ability of patients with Alzheimer's disease (AD), so as to evaluate its clinical efficacy. METHODS: Sixty AD patients were collected and randomly divided into control group (30 cases) and observation group (30 cases). Patients in the control group were treated with oral donepezil hydrochloride (5 mg, once daily). Patients in the observation group were treated with scalp-abdominal acupuncture at Baihui (GV20), Yintang (GV24+), Sishencong (EX-HN1), "emotional area", Shenting (GV24), "abdominal area 1""abdominal area 8", and bilateral Fengchi (GB20), Taixi (KI3), Xuanzhong (GB39), Zusanli (ST36) on the basis of control group, and electroacupuncture (10 Hz/50 Hz, 0.5 to 5.0 mA) was applied to EX-HN1, "emotional area""abdominal area 1" and "abdominal area 8", once daily, 30 min each time. Four weeks as a course of treatment, both the two groups were treated for two consecutive courses. Before and after treatment, the mini-mental state examination (MMSE), AD assessmennt scale-cognitive subscale (ADAS-Cog) and activity of daily living scale (ADL) were evaluated. The clinical efficacy index was calculated and safety was evaluated. RESULTS: After treatment, the MMSE and ADL scores were higher (P<0.05) and the ADAS-Cog score was lower (P<0.05) than those before treatment in both groups. Compared with the control group, the MMSE and ADL scores were increased (P<0.05) and ADAS-Cog score was decreased (P<0.05) in the observation group. The total effective rate of the observation group (26/30, 86.67%) was higher (P<0.05) than that of the control group (23/30, 76.67%). No adverse reactions occurred in both groups during the treatment. CONCLUSIONS: Scalp-abdominal acupuncture combined with donepezil hydrochloride can effectively improve the cognitive ability and daily living ability of AD patients, and the efficacy is better than that of oral donepezil hydrochloride alone.

Fungal biomineralization of toxic metals accelerates organic pollutant removal.

Fungal biomineralization plays an important role in the biogeochemical cycling of metals in the environment and has been extensively explored for bioremediation and element biorecovery. However, the cellular and metabolic responses of fungi in the presence of toxic metals during biomineralization and their impact on organic matter transformations are unclear. This is an important question because co-contamination by toxic metals and organic pollutants is a common phenomenon in the natural environment. In this research, the biomineralization process and oxidative stress response of the geoactive soil fungus Aspergillus niger were investigated in the presence of toxic metals (Co, Cu, Mn, and Fe) and the azo dye orange II (AO II). We have found that the co-existence of toxic metals and AO II not only enhanced the fungal biomineralization of toxic metals but also accelerated the removal of AO II. We hypothesize that the fungus and in situ mycogenic biominerals (toxic metal oxalates) constituted a quasi-bioreactor, where the biominerals removed organic pollutants by catalyzing reactive oxygen species (ROS) generation resulting from oxidative stress. We have therefore demonstrated that a fungal/biomineral system can successfully achieve the goal of toxic metal immobilization and organic pollutant decomposition. Such findings inform the potential development of fungal-biomineral hybrid systems for mixed pollutant bioremediation as well as provide further understanding of fungal organic-inorganic pollutant transformations in the environment and their importance in biogeochemical cycles.

Design, synthesis, and biological evaluation of novel benzimidazole derivatives as anti-cervical cancer agents through PI3K/Akt/mTOR pathway and tubulin inhibition.

Phosphatidylinositol 3-kinase (PI3K) is one of the most attractive therapeutic targets for cervical cancer treatment. In this study, we designed and synthesized a series of benzimidazole derivatives and evaluated their anti-cervical cancer activity. Compound 4r exhibited strong antiproliferative activity in different cervical cancer cell lines HeLa, SiHa and Ca Ski, and relative lower cytotoxicity to normal hepatic and renal cell lines LO2 and HEK-293t (IC50 values were at 21.08 µM and 23.96 µM respectively). Its IC50 value was at 3.38 µM to the SiHa cells. Further mechanistic studies revealed that 4r induced apoptosis, arrested cell cycle in G2/M phase, suppressed PI3K/Akt/mTOR pathway and inhibit the polymerization of tubulin. Molecular docking study suggested that 4r formed key H-bonds action with PI3Kα (PDB ID:8EXU) and tubulin (PDB ID:1SA0). Zebrafish acute toxicity experiments showed that high concentrations of 4r did not cause death or malformation of zebrafish embryos. All these results demonstrated that 4r would be a promising lead candidate for further development of novel PI3K and tubulin dual inhibitors in cervical cancer treatment.

Genome-wide identification and characterization of the sweet orange (Citrus sinensis) basic helix-loop-helix (bHLH) family reveals a role for CsbHLH085 as a regulator of citrus bacterial canker resistance.

Citrus bacterial canker (CBC) is a harmful bacterial disease caused by Xanthomonas citri subsp. citri (Xcc), negatively impacting citrus production worldwide. The basic helix-loop-helix (bHLH) transcription factor family plays crucial roles in plant development and stress responses. This study aimed to identify and annotate bHLH proteins encoded in the Citrus sinensis genome and explore their involvement and functional importance in regulating CBC resistance. A total of 135 putative CsbHLHs TFs were identified and categorized into 16 subfamilies. Their chromosomal locations, collinearity, and phylogenetic relationships were comprehensively analyzed. Upon Xcc strain YN1 infection, certain CsbHLHs were differentially regulated in CBC-resistant and CBC-sensitive citrus varieties. Among these, CsbHLH085 was selected for further functional characterization. CsbHLH085 was upregulated in the CBC-resistant citrus variety, was localized in the nucleus, and had a transcriptional activation activity. CsbHLH085 overexpression in Citrus significantly enhanced CBC resistance, accompanied by increased levels of salicylic acid (SA), jasmonic acid (JA), reactive oxygen species (ROS), and decreased levels of abscisic acid (ABA) and antioxidant enzymes. Conversely, CsbHLH085 virus-induced gene silencing resulted in opposite phenotypic and biochemical responses. CsbHLH085 silencing also affected the expression of phytohormone biosynthesis and signaling genes involved in SA, JA, and ABA signaling. These findings highlight the crucial role of CsbHLH085 in regulating CBC resistance, suggesting its potential as a target for biotechnological-assisted breeding citrus varieties with improved resistance against phytopathogens.

Dietary Hemin Remodels Gut Microbiota and Mediates Tissue Inflammation and Injury in the Small Intestine.

SCOPE: Epidemiological studies have linked excessive red and processed meat intake to gut disorders. Under laboratory conditions, high heme content is considered the primary health risk factor for red meat. However, heme in meat is present in myoglobin, which is an indigestible protein, suggesting the different functions between myoglobin and heme. This study aims to explore how dietary myoglobin and heme affect gut health and microbiota differently. METHODS AND RESULTS: Histological and biochemical assessments as well as 16S rRNA sequencing are performed. Moderate myoglobin intake (equivalent to the recommended intake of 150 g meat per day for human) has beneficial effects on the duodenal barrier. However, a too high myoglobin diet (equivalent to intake of 3000 g meat per day for human) triggers duodenum injury and alters the microbial community. The hemin diet destroys intestinal tissue and ileal microbiota more significantly. The in vitro experiments further confirm that free heme exhibits high toxicity to beneficial gut bacteria while myoglobin promotes the growth and metabolism of Limosilactobacillus reuteri. CONCLUSION: Moderate intake of myoglobin or hemin is beneficial to intestinal health and microbiota, but too high amounts lead to tissue inflammation and injury in the small intestine by reshaping ileal microbiota.