Overexpressed Artificial Spidroin Based Microneedle Spinneret for 3D Air Spinning of Hybrid Spider Silk.

Efforts have been devoted to developing strategies for converting spider silk proteins (spidroins) into functional silk materials. However, studies mimicking the exact natural spinning process of spiders encounter arduous challenges. In this paper, consistent with the natural spinning process of spiders, we report a high-efficient spinning strategy that enables the mass preparation of multifunctional artificial spider silk at different scales. By simulating the structural stability mechanism of the cross-ß-spine of the amyloid polypeptide by computer dynamics, we designed and obtained an artificial amyloid spidroin with a significantly increased yield (13.5 g/L). Using the obtained artificial amyloid spidroin, we fabricated artificial spiders with artificial spinning glands (hollow MNs). Notably, by combining artificial spiders with 3D printing, we perform patterned air spinning at the macro- and microscales, and the resulting patterned artificial spider silk has excellent pump-free liquid flow and conductive and frictional electrical properties. Based on these findings, we used macroscale artificial spider silk to treat rheumatoid arthritis in mice and micro artificial spider silk to prepare wound dressings for diabetic mice. We believe that artificial spider silk based on an exact spinning strategy will provide a high-efficient way to construct and modulate the next generation of smart materials.

Application Value and Safety Analysis of Warfarin, Rivaroxaban, and Dabigatran Ester in Elderly Patients With Atrial Fibrillation.

BACKGROUND: This study aimed to evaluate the application value and safety of Warfarin, Rivaroxaban, and Dabigatran in elderly patients with atrial fibrillation. METHODS: A total of 180 elderly patients with atrial fibrillation admitted to our hospital were retrospectively analyzed. According to their anticoagulant treatment regimen, patients were divided into three groups: Warfarin (57 cases), Rivaroxaban (61 cases), and Dabigatran (62 cases). General demographic information was collected, and coagulation function indicators-including fibrinogen (FIB), thrombin time (PT), activated partial thrombin time (APTT), and D-dimer (D-D)-as well as liver function indexes-including total bilirubin (TbiL), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine transferase (ALT)-were compared before and after 4 weeks of treatment. RESULTS: There were no significant differences in demographic characteristics such as gender, age, body mass index, or disease course among the three groups. The total effective rate in the Warfarin group (84.21%) was significantly lower than in the Rivaroxaban (98.36%) and Dabigatran (96.77%) groups (p < 0.05). However, there was no significant difference in the total effective rate between the Rivaroxaban and Dabigatran groups (p > 0.05). Additionally, no significant differences were found in the effects of the three drugs on coagulation function, liver function, or the incidence of bleeding (p = 0.052). CONCLUSION: Warfarin, Rivaroxaban, and Dabigatran can effectively prevent thrombosis in elderly patients with atrial fibrillation, with Rivaroxaban and Dabigatran showing superior effectiveness. All three drugs demonstrated similar low rates of bleeding events and had no significant impact on coagulation and liver function.

Associations between different insulin resistance indices and the risk of all-cause mortality in peritoneal dialysis patients.

BACKGROUND: Insulin resistance (IR) is prevalent in individuals undergoing peritoneal dialysis (PD) and is related to increased susceptibility to coronary artery disease and initial peritonitis. In recent investigations, correlations have been found between indices of IR and the incidence of all-cause mortality in various populations. However, such correlations have not been detected among individuals undergoing PD. Hence, the present study's aim was to explore the connections between IR indices and the incidence of all-cause mortality in PD patients. METHODS: Peritoneal dialysis patients (n = 1736) were recruited from multiple PD centres between January 2010 and December 2021. Cox proportional hazards and restricted cubic spline regression models were used to evaluate the connections between the triglyceride-glucose (TyG) index, triglyceride-glucose/body mass index (TyG-BMI), and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and the occurrence of all-cause mortality. All three IR indices were integrated into the same model to assess the predictive stability. Furthermore, a forest plot was employed to display the findings of the subgroup analysis of PD patients. RESULTS: Overall, 378 mortality events were recorded during a median follow-up time of 2098 days. Among PD patients, a higher TyG index, TyG-BMI, and TG/HDL-C ratio were identified as independent risk factors for all-cause mortality according to Cox proportional hazards analyses (hazard ratio (HR) 1.588, 95% confidence interval (CI) 1.261-2.000; HR 1.428, 95% CI 1.067-1.910; HR 1.431, 95% CI 1.105-1.853, respectively). In a model integrating the three IR indices, the TyG index showed the highest predictive stability. According to the forest plot for the TyG index, no significant interactions were observed among the subgroups. CONCLUSION: Significant associations were found between the TyG index, TyG-BMI, and TG/HDL-C ratio and the incidence of all-cause mortality among PD patients. The TyG index may be the most stable of the three surrogate IR markers. Finally, a correlation was identified between IR and the risk of all-cause mortality in patients undergoing PD.

Ubiquitin-specific protease 22 controls melanoma metastasis and vulnerability to ferroptosis through targeting SIRT1/PTEN/PI3K signaling.

Metastasis is a major contributing factor that affects the prognosis of melanoma patients. Nevertheless, the underlying molecular mechanisms involved in melanoma metastasis are not yet entirely understood. Here, we identified ubiquitin-specific protease 22 (USP22) as a pro-oncogenic protein in melanoma through screening the survival profiles of 52 ubiquitin-specific proteases (USPs). USP22 demonstrates a strong association with poor clinical outcomes and is significantly overexpressed in melanoma. Ablation of USP22 expression remarkably attenuates melanoma migration, invasion, and epithelial-mesenchymal transition in vitro and suppresses melanoma metastasis in vivo. Mechanistically, USP22 controls melanoma metastasis through the SIRT1/PTEN/PI3K pathway. In addition, we conducted an United States Food and Drug Administration-approved drug library screening and identified topotecan as a clinically applicable USP22-targeting molecule by promoting proteasomal degradation of USP22. Finally, we found that both pharmacological and genetic silence of USP22 sensitize RSL3-induced ferroptosis through suppressing the PI3K/Akt/mTOR pathway and its downstream SCD, and ferroptosis inhibitor could partly rescued the decreased lung metastasis by topotecan in vivo. Overall, our findings reveal a prometastatic role of USP22 and identify topotecan as a potent USP22-targeting drug to limit melanoma metastasis.

Multiphoton tandem photoredox catalysis of [Ir(dFCF3ppy)2(dtbbpy)]+ facilitating radical acylation reactions.

Photoredox catalytic radical acylation reactions, utilizing [Ir(dFCF3ppy)2(dtbbpy)]+ (IrIII) as the photocatalyst and α-keto acids as the starting substrates, have recently emerged as an attractive strategy for preparing ketone derivatives. While there is consensus on the importance of detailed mechanistic insights to maximize the formation of desired products, efforts focused on uncovering the underlying elementary mechanisms of IrIII photocatalytic radical acylation reactions are still lacking. Herein, using time-resolved spectroscopy, we observed the efficient quenching of the triplet state, 3IrIII*, via electron transfer from α-keto acids, resulting in the generatation of the reduced IrII. Subsequently, IrII rapidly transforms into a stable IrH+ species through protonation, with α-keto acid acting as a proton donor. Upon absorbing additional photon(s), IrH+ is expected to transform into IrH3, involving further hydrogenation/protonation. Emission and Fourier transform infrared (FTIR) spectroscopy, together with global analysis, identify the character of IrH3/3IrH3* and corroborate its contribution to representative radical acylation reactions (decarboxylative 1,4-addition of α-keto acids with Michael acceptors, decarboxylative coupling of α-keto acids with aryl halides, and decarboxylative cyclization of 2-alkenylarylisocyanides with α-keto acids), where IrH3/3IrH3* serves as the key species to trigger the second photoredox cycle. These results elucidate the existence and generality of the tandem photoredox catalysis mechanism for IrIII photocatalytic radical acylation reactions, providing advanced insights into the mechanism of IrIII-based photoredox processes and potentially expanding their application in the design and development of new synthetic methodologies.

Metabolomic analysis revealed the inflammatory and oxidative stress regulation in response to Vibrio infection in Plectropomus leopardus.

Frequent outbreaks of infectious diseases in aquaculture have led to significant economic losses. The leopard coral grouper (Plectropomus leopardus) often suffers from vibriosis. Improving host immunity presents a superior strategy for disease control, with minimal side effects compared to the use of antibiotics, highlighting the necessity of exploring the mechanisms underlying the fish's response to pathogen infections. Here, we conducted a comparative metabolomic analysis on the livers of the P. leopardus infected with Vibrio harveyi. A total of 1124 differential metabolites (DMs) were identified, with 190, 218, 359, and 353 DMs being identified at 6, 12, 24, and 48 h post-infection (hpi), respectively. Then, based on the time series analysis, we found that the lipid metabolism pathways were modulated in response to the Vibrio infection, with an increase in the quantity of eicosanoids and gycerophospholipids (GPLs), as well as a decrease in the quantity of bile acids (BAs), vitamin D, and sex hormones. Furthermore, 13 enriched pathways involving 31 DMs were identified through KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses. We identified histamine, 15(S)-HpETE, and anandamide in the transient receptor potential (TRP) channels pathway, as well as (7S,8S)-DiHODE, 5S,8R-DiHODE, and 13(S)-HpODE in the linoleic acid (LA) metabolism pathway. The DM levels increased, which may be attributed to inflammation. The DMs in the thyroid hormone synthesis pathway were identified, and the contents of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) decreased, which may be crucial in antioxidants. Our findings highlighted the dynamic adjustments in lipid metabolism and the response to inflammation and oxidative stress during the infection of V. harveyi in P. leopardus. This study not only deepens our understanding of the metabolic underpinnings of fish immune responses but also lays the groundwork for research into functional metabolomics and mechanisms of disease resistance.

Assessment of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and systemic immune-inflammatory index, as diagnostic markers for neonatal sepsis.

OBJECTIVE: To assess the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic immune-inflammatory index (SII), as diagnostic markers for neonatal sepsis. METHODS: This retrospective study involve neonates with sepsis and healthy neonates as controls. NLR, PLR, and SII were compared between groups. RESULT: In total, 60 neonates with sepsis and 60 healthy controls were involved in the study. Compared with controls, the sepsis group had higher values for NLR, PLR and SII. Logistic regression analysis suggested that the NLR, PLR and SII were independent risk factors for neonatal sepsis. In addition, receiver operating characteristic (ROC) curve analysis indicated that the NLR, PLR and SII were reliable predictors of neonatal sepsis and SII had the best predictive value. CONCLUSIONS: NLR, PLR and SII appear to be useful indicators for predicting neonatal sepsis.

Optimization of the extraction process of total steroids from Phillinus gilvus (Schwein.) Pat. by artificial neural network (ANN)-response surface methodology and identification of extract constituents.

Phillinus gilvus (Schwein.) Pat has pharmacological effects such as tonifying the spleen, dispelling dampness, and strengthening the stomach, in which sterol is one of the main compounds of P. gilvus, but there has not been thought you to its extraction and detailed identification of its composition, in the present study, we used artificial neural network (ANN) and response surface methodology (RSM) to optimize the conditions of ultrasonic-assisted extraction, and the parameters of the independent and interaction effects were evaluated. Ultra performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) was used to identify the major components in the purified extract. The results showed that the optimal extraction process conditions were: ultrasonic time 96 min, ultrasonic power 140 W, liquid to material ratio 1:25 g/ml, and ultrasonic temperature 30.7 °C. The compliance rates of the predicted and experimental values for the artificial neural network model and the response surface model were 98.3% and 96.12%, respectively, indicating that both models have the potential to be used for optimizing the extraction process of P. gilvus in industry. A total of 120 compounds and 30 major steroids were identified by comparison with the reference compounds. Among the major steroidal components are these findings will contribute to the isolation and utilization of active ingredients in P. gilvus.

Modulating d-Orbital electronic configuration via metal-metal oxide interactions for boosting electrocatalytic methanol oxidation.

Coordinating the interfacial interaction between Pt-based nanoparticles (NPs) and supports is a significant strategy for the modulation of d-orbital electronic configuration and the adsorption behaviors of intermediates, which is of critical importance for boosting electrocatalytic performance. Herein, we demonstrated a specific synergy effect between the ordered PtFe intermetallic and neighboring oxygen vacancies (Ov), which provides an "ensemble reaction pool" to balance the barriers of both the activity, stability, and CO poisoning issues for the methanol oxidation reaction (MOR). In our proposed "ensemble reaction pool", the deprotonation of methanol occurs on the Pt site to form the intermediate *CO, where the strain derived from the PtFe intermetallic could alter the d-orbital electronic configuration of Pt, intrinsically weakening the *CO adsorption energy, and Ov in CeO2 promote hydroxyl species (*OH) adsorption, which will react with *CO, facilitating the dissociative adsorption of *CO, thus cooperatively enhancing the performance of MOR. The X-ray absorption fine structure (XAFS) analyses reveal the electron transfer in CeO2 and then convert Ce4+ to Ce3+. The density functional theory (DFT) calculations revealed that introducing Fe induces strain could modify the d-band center of Pt, and thus lower the energy barrier of the potential-determining step. Meanwhile, the introduction of CeO2 can favor the *OH adsorption, speeding up the oxidation and removal of *CO blocked at the Pt site. Furthermore, the determined atomic arrangement and surface composition of PtFe intermetallic further guarantee the stability of MOR by suppressing less-noble metal into the electrolyte.

Orbital electron delocalization of axial-coordinated modified FeN4 and structurally ordered PtFe intermetallic synergistically for efficient oxygen reduction reaction catalysis.

Regulating the chemical environment of materials to optimize their electronic structure, leading to the optimal adsorption energies of intermediates, is of paramount importance to improving the performance of electrocatalysts, yet remains an immense challenge. Herein, we design a harmonious axial-coordination Pt x Fe/FeN4CCl catalyst that integrates a structurally ordered PtFe intermetallic with an orbital electron-delocalization FeN4CCl support for synergistically efficient oxygen reduction catalysis. The obtained Pt2Fe/FeN4CCl with a favorable atomic arrangement and surface composition exhibits enhanced oxygen reduction reaction (ORR) intrinsic activity and durability, achieving a mass activity (MA) and specific activity (SA) of 1.637 A mgPt -1 and 2.270 mA cm-2, respectively. Detailed X-ray absorption fine spectroscopy (XAFS) further confirms the axial-coupling effect of the FeN4CCl substrate by configuring the Fe-N bond to ∼1.92 Å and the Fe-Cl bond to ∼2.06 Å. Additionally, Fourier transforms of the extended X-ray absorption fine structure (FT-EXAFS) demonstrate relatively prominent peaks at ∼1.5 Å, ascribed to the contribution of the Fe-N/Fe-Cl, further indicating the construction of the FeN4CCl moiety structure. More importantly, the electron localization function (ELF) and density functional theory (DFT) further determine an orbital electron delocalization effect due to the strong axial traction between the Cl atoms and FeN4, resulting in electron redistribution and modification of the coordination surroundings, thus optimizing the adsorption free energy of OHabs intermediates and effectively accelerating the ORR catalytic kinetic process.

KCNE4 is a crucial host factor for Orf virus infection by mediating viral entry.

The orf virus (ORFV) poses a serious threat to the health of domestic small ruminants (i.e., sheep and goats) and humans on a global scale, causing around $150 million in annual losses to livestock industry. However, the host factors involved in ORFV infection and replication are still elusive. In this study, we compared the RNA-seq profiles of ORFV-infected or non-infected sheep testicular interstitial cells (STICs) and identified a novel host gene, potassium voltage-gated channel subfamily E member 4 (KCNE4), as a key host factor involved in the ORFV infection. Both RNA-seq data and RT-qPCR assay revealed a significant increase in the expression of KCNE4 in the infected STICs from 9 to 48 h post infection (hpi). On the other hand, the RT-qPCR assay detected a decrease in ORFV copy number in both the STICs transfected by KCNE4 siRNA and the KCNE4 knockout (KO) HeLa cells after the ORFV infection, together with a reduced fluorescence ratio of ORFV-GFP in the KO HeLa cells at 24 hpi, indicating KCNE4 to be critical for the ORFV infection. Furthermore, the attachment and internalization assays showed decreased ORFV attachment, internalization, replication, and release by the KO HeLa cells, demonstrating a potential inhibition of ORFV entry into the cells by KCNE4. Pretreatment with the KCNE4 inhibitors such as quinidine and fluoxetine significantly repressed the ORFV infection. All our findings reveal KCNE4 as a novel host regulator of the ORFV entry and replication, shedding new insight into the interactive mechanism of ORFV infection. The study also highlights the K+ channels as possible druggable targets to impede viral infection and disease.

Spatiotemporal expression analysis of jasmonic acid and saponin-related genes uncovers a potential biosynthetic regulation in Panax notoginseng.

BACKGROUND: Sanqi, the root of Panax notoginseng, has long been recognized for its therapeutic effects on cardiovascular diseases. Saponins, including ginsenosides and notoginsenosides, are the main bioactive components of P. notoginseng. The biosynthesis of saponins is closely related to the defense responses orchestrated by endogenous hormones. RESULTS: To provide new insights into the underlying role of phytohormone jasmonic acid (JA) in the synthesis and regulation of saponins, we performed an ultra-performance liquid chromatography analysis of different tissues of P. notoginseng aged 2-4 years. Moreover, by combined evaluation of saponin content and transcriptome profiling of each tissue, the spatial and temporal distribution of saponins was analyzed. N notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rd accumulated in the underground tissues, including the root, tuqi, fibril and rhizome. In agreement with this data, the corresponding genes of the endogenous hormone JAs, especially coronatine insensitive 1 (COI1) and myelocytomatosis proteins 2 (MYC2), were predominantly expressed in the underground tissues. The tissue- and age-specific distribution of saponins was consistent with the expression of genes involved in JA biosynthetic, metabolic and signaling pathways. CONCLUSION: The present study has revealed the temporal and spatial effects of endogenous phtohormones in the synthesis and regulation of notoginsenosides, which will provide a significant impact on improving the ecological planting technology, cultivating new high-quality varieties and protecting the rare resources of medicinal P. notoginseng. © 2024 Society of Chemical Industry.

NAD+ deficiency primes defense metabolism via 1O2-escalated jasmonate biosynthesis in plants.

Nicotinamide adenine dinucleotide (NAD+) is a redox cofactor and signal central to cell metabolisms. Disrupting NAD homeostasis in plant alters growth and stress resistance, yet the underlying mechanisms remain largely unknown. Here, by combining genetics with multi-omics, we discover that NAD+ deficiency in qs-2 caused by mutation in NAD+ biosynthesis gene-Quinolinate Synthase retards growth but induces biosynthesis of defense compounds, notably aliphatic glucosinolates that confer insect resistance. The elevated defense in qs-2 is resulted from activated jasmonate biosynthesis, critically hydroperoxidation of α-linolenic acid by the 13-lipoxygenase (namely LOX2), which is escalated via the burst of chloroplastic ROS-singlet oxygen (1O2). The NAD+ deficiency-mediated JA induction and defense priming sequence in plants is recapitulated upon insect infestation, suggesting such defense mechanism operates in plant stress response. Hence, NAD homeostasis is a pivotal metabolic checkpoint that may be manipulated to navigate plant growth and defense metabolism for stress acclimation.

The correlation between mitochondrial derived peptide (MDP) and metabolic states: a systematic review and meta-analysis.

BACKGROUND: MOTS-c is known as mitochondrial open reading frame (ORF) of the twelve S c, produced by a small ORF-encoded peptides (SEPs) in mitochondrial 12S rRNA region. There is growing evidence that MOTS-c has a strong relationship with the expression of inflammation- and metabolism-associated genes and metabolic homeostasis, and even offering some protection against insulin resistance (IR). However, studies have reported inconsistent correlations between different population characteristics and MOTS-c levels. This meta-analysis aims to elucidate MOTS-c levels in physiological and pathological states, and its correlation with metabolic features in various physiological states. METHODS: We conducted a systematic review and meta-analysis to synthesize the evidence of changes in blood MOTS-c concentration, and any association between MOTS-c and population characteristic. The Web of Science, PubMed, EMBASE, CNKI, WANGFANG and VIP databases were searched from inception to April 2023. The statistical analysis was summarized using the standardized mean difference (SMD) and 95% confidence interval (95% CIs). Pearson correlation coefficient was used to analyze the correlation and generate forest plots through a random-effects model. Additional analyses as sensitivity and subgroup analyses were performed to identify the origins of heterogeneity. Publication bias was retrieved by means of a funnel-plot analysis and Egger's test. All related statistical analyses were performed using Revman 5.3 and Stata 15 statistical software. RESULT: There are 6 case-control studies and 1 cross-sectional study (11 groups) including 602 participants in our current meta-analysis. Overall analysis results showed plasma MOTS-c concentration in diabetes and obesity patients was significantly reduced (SMD = - 0.37; 95% CI- 0.53 to - 0.20; P < 0.05). After subgroup analysis, the present analysis has yielded opposite results for MOTS-c changes in obesity (SMD = 0.51; 95% CI 0.21 to 0.81; P < 0.05) and type 2 diabetes mellitus (T2DM) (SMD = - 0.89; 95% CI - 1.12 to - 0.65; P < 0.05) individuals. Moreover, the correlation analysis was performed to identify that MOTS-c levels were significantly positively correlated with TC (r = 0.29, 95% CI 0.20 to 0.38) and LDL-c (r = 0.30, 95% CI 0.22 to 0.39). The subgroup analysis results showed that MOTS-c decreased significantly in patients with diabetes (SMD = - 0.89; 95% CI- 1.12 to - 0.65; P < 0.05). In contrast, the analysis result for obesity persons (BMI > 28 kg/ m2) was statistically significant after overweight people (BMI = 24-28 kg/ m2) were excluded (SMD = 0.51; 95% CI 0.21 to 0.81; P < 0.05), which is completely different from that of diabetes. Publication bias was insignificant (Egger's test: P = 0.722). CONCLUSION: Circulating MOTS-c level was significantly reduced in diabetic individuals but was increased significantly in obesity patients. The application of monitoring the circulating levels variability of MOTS-c in routine screening for obesity and diabetes is prospects and should be taken into consideration as an important index for the early prediction and prevention of metabolic syndrome in the future. PROSPERO registration number CRD42021248167.

Human/mouse CD137 agonist, JNU-0921, effectively shrinks tumors through enhancing the cytotoxicity of CD8+ T cells in cis and in trans.

Agonistic antibodies against CD137 have been demonstrated to completely regress established tumors through activating T cell immunity. Unfortunately, current CD137 antibodies failed to benefit patients with cancer. Moreover, their antitumor mechanisms in vivo remain to be determined. Here, we report the development of a small molecular CD137 agonist, JNU-0921. JNU-0921 effectively activates both human and mouse CD137 through direct binding their extracellular domains to induce oligomerization and signaling and effectively shrinks tumors in vivo. Mechanistically, JNU-0921 enhances effector and memory function of cytotoxic CD8+ T cells (CTLs) and alleviates their exhaustion. JNU-0921 also skews polarization of helper T cells toward T helper 1 type and enhances their activity to boost CTL function. Meanwhile, JNU-0921 attenuates the inhibitory function of regulatory T cells on CTLs. Our current work shows that JNU-0921 shrinks tumors by enhancing the cytotoxicity of CTLs in cis and in trans and sheds light on strategy for developing CD137 small molecular agonists.

HS-GC-IMS Analysis of Volatile Organic Compounds in Six Spicy Spices and Their Effects on Ulcerative Colitis.

The volatile organic compounds of six spices, including black pepper, dried ginger, cinnamon, fennel, clove, and zanthoxylum, were analyzed by gas chromatography-ion mobility spectrometry (HS-GC-IMS) combined with principal component analysis (PCA) and Euclidean distance. In further analyses, the effects of volatile oils in six spices on ulcerative colitis were assayed in a zebrafish model induced by 3-nitrobenzenesulfonic acid. A total of 120 kinds of volatile organic compounds were detected and 80 among them were identified, which included 10 common components and 3 to 24 characteristic components belonging to different spices. The major VOCs in six spices were estimated to be terpenes with the contents of 45.02%, 56.87%, 36.68%, 58.19%, 68.68%, and 30.62%, respectively. Meanwhile, the volatile components of fennel, dried ginger, black pepper, and cinnamon are quite similar, but differ from clove and zanthoxylum. The volatile oils in six spices presented efficient activity to improve ulcerative colitis which can decrease the number of neutrophils, restore the structure of intestinal epithelial and the morphology of the epithelial cells. Our study achieved rapid analysis of the volatile organic compounds and flavors in six spices and further revealed the potential health benefits of their volatile oils on ulcerative colitis, especially for clove and zanthoxylum. This study is expected to provide certain data support for the quality evaluation and the potential use in functional foods of six spices.

Fluoroamphiphilic polymers exterminate multidrug-resistant Gram-negative ESKAPE pathogens while attenuating drug resistance.

ESKAPE pathogens are a panel of most recalcitrant bacteria that could "escape" the treatment of antibiotics and exhibit high incidence of drug resistance. The emergence of multidrug-resistant (MDR) ESKAPE pathogens (particularly Gram-negative bacteria) accounts for high risk of mortality and increased resource utilization in health care. Worse still, there has been no new class of antibiotics approved for exterminating the Gram-negative bacteria for more than 50 years. Therefore, it is urgent to develop novel antibacterial agents with low resistance and potent killing efficacy against Gram-negative ESKAPE pathogens. Herein, we present a class of fluoropolymers by mimicking the amphiphilicity of cationic antimicrobial peptides. Our optimal fluoroamphiphilic polymer (PD45HF5) displayed selective antimicrobial ability for all MDR Gram-negative ESAKPE pathogens, low resistance, high in vitro cell selectivity, and in vivo curative efficacy. These findings implied great potential of fluoroamphiphilic cationic polymers as promising antibacterial agents against MDR Gram-negative ESKAPE bacteria and alleviating antibiotic resistance.

Treatment of vedolizumab with exclusive enteral nutrition in adult patients with moderate to severe Crohn's Disease (CEEN Study).

BACKGROUND: Despite increasing studies confirming the efficacy of vedolizumab in Crohn's disease (CD), improving the responses to this biologic agent remains challenging in clinical practice. Here, we investigated the efficacy of combined treatment of vedolizumab and 16-week exclusive enteral nutrition (EEN) in moderately to severely active CD. METHODS: From October 2020 to October 2023, 81 patients with moderately to severely active CD treated with vedolizumab from three IBD centers were retrospectively selected. Forty-one patients received treatment of vedolizumab with concomitant 16-week EEN (vedolizumab, VDZ+EEN cohort) and 40 patients received vedolizumab treatment alone (VDZ cohort). Clinical and biological outcomes were evaluated. Endoscopic response and mucosal healing were assessed by colonoscopy at week 16 and 52. RESULTS: There was no statistically significant difference between two groups at baseline for demographic and clinical characteristics. Compared to patients treated with vedolizumab alone, patients in the VDZ+EEN cohort achieved higher rates of clinical response (84.2% vs. 40.0%), clinical remission (81.6% vs. 30.0%), endoscopic response (91.4 % vs. 34.6%) including mucosal healing (85.7% vs. 26.9%) at week 16. The superiority of VDZ+EEN treatment sustained in maintenance, with 76.7% (vs. 33.3%) clinical response, 70.0% (vs. 26.7%) clinical remission, 76.9% (vs. 33.3%) endoscopic response, and 61.5% (vs. 26.7%) mucosal healing at week 52. None of patients experienced severe adverse events. CONCLUSION: Vedolizumab with concomitant 16-week EEN might be an effective and optimized approach with solid efficacy in the induction and maintenance treatment of active CD.

Two colistin resistance-producing Aeromonas strains, isolated from coastal waters in Zhejiang, China: characteristics, multi-drug resistance and pathogenicity.

Introduction: Aeromonas spp. are ubiquitous inhabitants of ecosystems, and many species are opportunistically pathogenic to humans and animals. Multidrug-resistant (MDR) Aeromonas species have been widely detected in hospitals, urban rivers, livestock, and aquatic animals. Results: In this study, we identified two Aeromonas isolates, namely Aeromonas veronii 0728Q8Av and Aeromonas caviae 1029Y16Ac, from coastal waters in Zhejiang, China. Both isolates exhibited typical biochemical characteristics and conferred MDR to 11 kinds of antibiotics, remaining susceptible to ceftazidime. Whole-genome sequencing revealed that both isolates harbored multiple antibiotic resistance genes (ARGs) and several mobile genetic elements (MGEs) on the chromosomes, each containing a resistance genomic island (GI), a typical class 1 integron, a transposon, and various insertion sequences (ISs). Most ARGs were situated within the multiple resistance GI, which contained a class 1 integron and a transposon in both Aeromonas isolates. Furthermore, a chromosomal mcr-3.16 gene was identified in A. veronii 0728Q8Av, while a chromosomal mcr-3.3 was found in A. caviae 1029Y16Ac. Both mcr-3 variants were not located within but were distanced from the multidrug resistance GI on the chromosome, flanking by multiple ISs. In addition, a mcr-3-like was found adjacent to mcr-3.16 to form a tandem mcr-3.16-mcr-3-like-dgkA structure; yet, Escherichia coli carrying the recombinants of mcr-3-like did not exhibit resistance to colistin. And an incomplete mcr-3-like was found adjacent to mcr-3.3 in A. caviae 1029Y16Ac, suggesting the possibility that mcr-3 variants originated from Aeromonas species. In vivo bacterial pathogenicity test indicated that A. veronii 0728Q8Av exhibited moderate pathogenicity towards infected ayu, while A. caviae 1029Y16Ac was non-virulent. Discussion: Thus, both Aeromonas species deserve further attention regarding their antimicrobial resistance and pathogenicity.

Decoding the fish genome opens a new era in important trait research and molecular breeding in China.

Aquaculture represents the fastest-growing global food production sector, as it has become an essential component of the global food supply. China has the world's largest aquaculture industry in terms of production volume. However, the sustainable development of fish culture is hindered by several concerns, including germplasm degradation and disease outbreaks. The practice of genomic breeding, which relies heavily on genome information and genotypephenotype relationships, has significant potential for increasing the efficiency of aquaculture production. In 2014, the completion of the genome sequencing and annotation of the Chinese tongue sole signified the beginning of the fish genomics era in China. Since then, domestic researchers have made dramatic progress in functional genomic studies. To date, the genomes of more than 60 species of fish in China have been assembled and annotated. Based on these reference genomes, evolutionary, comparative, and functional genomic studies have revolutionized our understanding of a wide range of biologically and economically important traits of fishes, including growth and development, sex determination, disease resistance, metamorphosis, and pigmentation. Furthermore, genomic tools and breeding techniques such as SNP arrays, genomic selection, and genome editing have greatly accelerated genetic improvement through the incorporation of functional genomic information into breeding activities. This review aims to summarize the current status, advances, and perspectives of the genome resources, genomic study of important traits, and genomic breeding techniques of fish in China. The review will provide aquaculture researchers, fish breeders, and farmers with updated information concerning fish genomic research and breeding technology. The summary will help to promote the genetic improvement of production traits and thus will support the sustainable development of fish aquaculture.