SNX5-Rab11a protects against cardiac hypertrophy through regulating LRP6 membrane translocation.

BACKGROUNDS: Pathological cardiac hypertrophy is considered one of the independent risk factors for heart failure, with a rather complex pathogenic machinery. Sorting nexins (SNXs), denoting a diverse family of cytoplasmic- and membrane-associated phosphoinositide-binding proteins, act as a pharmacological target against specific cardiovascular diseases including heart failure. Family member SNX5 was reported to play a pivotal role in a variety of biological processes. However, contribution of SNX5 to the development of cardiac hypertrophy, remains unclear. METHODS: Mice underwent transverse aortic constriction (TAC) to induce cardiac hypertrophy and simulate pathological conditions. TAC model was validated using echocardiography and histological staining. Expression of SNX5 was assessed by western blotting. Then, SNX5 was delivered through intravenous administration of an adeno-associated virus serotype 9 carrying cTnT promoter (AAV9-cTnT-SNX5) to achieve SNX5 cardiac-specific overexpression. To assess the impact of SNX5, morphological analysis, echocardiography, histological staining, hypertrophic biomarkers, and cardiomyocyte contraction were evaluated. To unravel potential molecular events associated with SNX5, interactome analysis, fluorescence co-localization, and membrane protein profile were evaluated. RESULTS: Our results revealed significant downregulated protein level of SNX5 in TAC-induced hypertrophic hearts in mice. Interestingly, cardiac-specific overexpression of SNX5 improved cardiac function, with enhanced left ventricular ejection fraction, fraction shortening, as well as reduced cardiac fibrosis. Mechanistically, SNX5 directly bound to Rab11a, increasing membrane accumulation of Rab11a (a Rab GTPase). Afterwards, this intricate molecular interaction upregulated the membrane content of low-density lipoprotein receptor-related protein 6 (LRP6), a key regulator against cardiac hypertrophy. Our comprehensive assessment of siRab11a expression in HL-1 cells revealed its role in antagonism of LRP6 membrane accumulation under SNX5 overexpression. CONCLUSIONS: This study revealed that binding of SNX5 with LRP6 triggers their membrane translocation through Rab11a assisting, defending against cardiac remodeling and cardiac dysfunction under pressure overload. These findings provide new insights into the previously unrecognized role of SNX5 in the progression of cardiac hypertrophy.

Insight into the Imbibition Behavior of Low-Frequency Artificial Vibration Stimulation in Tight Sandstone.

Spontaneous imbibition is the primary mechanism responsible for the enhanced oil production in a tight reservoir after hydraulic fracturing. In this article, a low-frequency artificial vibration physics stimulation method was employed to evaluate the effect of low-frequency vibration on imbibition recovery in tight sandstones. Furthermore, a high-precision in situ computed tomography (CT) scan was employed to investigate the effect of low-frequency vibration on the distribution of remaining oil micro-occurrence dynamic alterations in pore space. The findings of the study show that (1) low-frequency artificial physical vibration stimulation has been found to be highly effective in enhancing imbibition recovery in tight sandstone. The sensitivity of the vibration parameters on imbibition recovery from highest to lowest is vibration frequency, vibration intensity, and vibration time. The optimum vibration parameters for this process are a vibration frequency of 30 Hz, a vibration intensity of 2.0 m/s2, and a vibration time of 30 h. (2) Under the optimum low-frequency vibration, the imbibition recovery of tight sandstone with various physical properties can reach between 13.6 and 28.3%. This is remarkably higher than the spontaneous imbibition recovery, which ranges from 9.4 to 17.1%. Additionally, core samples with higher permeability and better pore structure show a more significant increase in imbibition recovery under the vibration treatment. Furthermore, low-frequency vibration stimulation effectively shortens the imbibition completion time, reducing the completion time from 81 h to approximately 55 h. (3) After the spontaneous imbibition process, the initial continuous oil phase present in the pore space is dispersed by the water phase imbibition process. The remaining oil is dominant in the form of a network type, which is concentrated in the central pore space area of the core. Low-frequency vibration treatment can effectively promote a positive imbibition process. The network remaining oil saturation in the core can be further dispersed, especially closer to the surface of the core area after frequency vibration treatment. Then, the cluster remaining oil type with a more dispersed and simpler individual structure has become the new dominant remaining oil micro-occurrence form in the pore space. The findings of this research investigate a novel technological approach to enhance the imbibition efficiency of a tight sandstone reservoir.

Long-distance and high-precision ranging with dual-comb nonlinear asynchronous optical sampling.

Precise distance metrology and measurements play an important role in many fields of scientific research and industrial manufacture. Dual-comb laser ranging combines sub-wavelength ranging precision, large non-ambiguity range, and high update rate, making it the most promising candidate in precise distance metrology and measurements. However, previous demonstrations of dual-comb ranging suffer from short working distances, limited by the decoherence of lasers in interferometric schemes or by the low sensitivity of the photodetectors in response to the sparse echo photons. Here, we propose and demonstrate time-of-flight laser ranging with dual-comb nonlinear asynchronous optical sampling and photon counting by a fractal superconducting nanowire single-photon detector, achieving ranging precision of 6.2 micrometers with an acquisition time of 100 ms and 0.9 micrometers with an acquisition time of 1 s in measuring the distance of an outdoor target approximately 298 m away.

Multifunctional pH-responsive hydrogel dressings based on carboxymethyl chitosan: Synthesis, characterization fostering the wound healing.

Antibiotic abuse is increasing the present rate of drug-resistant bacterial wound infections, producing a significant healthcare burden globally. Herein, we prepared a pH-responsive CMCS/PVP/TA (CPT) multifunctional hydrogel dressing by embedding the natural plant extract TA as a nonantibiotic and cross-linking agent in carboxymethyl chitosan (CMCS) and polyvinylpyrrolidone (PVP) to prompt wound healing. The CPT hydrogel demonstrated excellent self-healing, self-adaptive, and adhesion properties to match different wound requirements. Importantly, this hydrogel showed pH sensitivity and exhibited good activity against resistant bacteria and antioxidant activity by releasing TA in case of bacterial infection (alkaline). Furthermore, the CPT hydrogel exhibited coagulant ability and could rapidly stop bleeding within 30 s. The biocompatible hydrogel effectively accelerated wound healing in a full-thickness skin defect model by thickening granulation tissue, increasing collagen deposition, vascular proliferation, and M2-type macrophage polarization. In conclusion, this study demonstrates that multifunctional CPT hydrogel offers a candidate material with potential applications for infected skin wound healing.

Dietary supplementation of Sida rhombifolia enhances the plasma antioxidation and modulates gut microbiota in Anyi tile-like grey chickens.

Sida rhombifolia (S. rhombifolia) is a widely used herbal plant for humans because of its antioxidant and antibacterial effects, but its potential use as a feed additive for livestock has not been investigated. Twenty 350 days-old Anyi tile-like grey chickens were randomly divided into a control group (fed basal diet) and a treatment group (fed basal diet + 3% of S. rhombifolia), and these chickens were feed for 31 days. Dietary S. rhombifolia remarkably enhanced plasma antioxidants, including the significantly increased total antioxidant capability (p < 0.01), catalase (p = 0.04), and superoxide dismutase (p < 0.01) in the treatment group. Furthermore, dietary S. rhombifolia also modulated chicken cecal microbiota, including an increased microbial diversity (Shannon, p = 0.03; Chao1, p = 0.03) in the treatment group. Regarding taxonomic analysis, 34 microbial taxa showed significant differences between the two groups. Meanwhile, the dominant phylum Actinobacteriota (p = 0.04), and dominant genera Desulfovibrio (p = 0.04) and Olsenella (p = 0.02) were significantly increased after treatment, whereas the pathogenic genus Escherichia-Shigella (p = 0.04) was significantly decreased after feeding S. rhombifolia. The results indicating that S. rhombifolia has potential for use as a natural plant feed additive for chickens.

Characterizing the relationship between MRI radiomics and AHR expression and deriving a predictive model for prognostic assessment in glioblastoma.

PURPOSE: Aryl hydrocarbon receptor (AHR), a crucial molecular marker associated with glioma, is a potential therapeutic target. We aimed to establish a non-invasive predictive model for AHR through radiomics. METHODS: Contrast-enhanced T1-weighted (T1W) MRI and the corresponding and clinical variables of glioblastoma patients from The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA) were obtained for analysis. KM curves and Cox regression analyses were used to assess the prognostic value of AHR expression. The radiomics features were screened by Max-Relevance and Min-Redundancy (mRMR) and recursive feature elimination (RFE), followed by the construction of two predictive models using logistic regression (LR) and a support vector machine (SVM). RESULTS: The expression levels of AHR in tumour patients were significantly higher than those in the control group, and higher AHR expression was associated with worse prognosis (P<0.05). AHR remained a risk factor for poor prognosis in glioblastoma after multivariate adjustment (HR: 1.61, 95% CI: 1.085-2.39, P<0.05). The radiomics models constructed using LR and SVM based on three selected features achieved area under the curve (AUC) values of 0.887 and 0.872, respectively. Radiomics score emerged as a key factor influencing overall survival (OS) after multivariate adjustment in the Cox model (HR: 3.931, 95% CI: 1.272-12.148, P < 0.05). CONCLUSION: The radiomics models could effectively distinguish the expression levels of AHR and predict prognosis in patients with glioblastoma, which may serve as a powerful tool to assist clinical assessment and precision treatment.

Comparing collagenase and silver sulfadiazine in deep second-degree burn treatment.

The indications for collagenase ointment (CO) and its efficacy are not clearly established in the treatment of second-degree burn wounds. To evaluate the efficacy of CO versus silver sulfadiazine ointment (SSD) in the treatment of second-degree burn wounds. A total of 170 eligible patients with deep second-degree burns, aged 18-65 years, with injuries occurring within 48-96 h, and having a total wound area of less than 30% of the total body surface area were included from 5 centers in China. The primary outcome was the wound healing time, and the secondary outcomes were the clearance time of wound necrotic tissues, wound healing rate, and wound inflammation. The study included 85 patients in SSD group and 84 in CO group in the modified intention-to-treat (mITT) population. The median time of wound healing was comparable in both groups (10 days vs. 10.5 days P = 0.16). The time for wound necrotic tissue removal was significantly shortened by CO compared with SSD (5 vs. 10 days P < 0.01). Wound inflammation, pain, wound healing rate, and scar were compared with SSD (all P-values > 0.05). No adverse events, such as infection or allergic reactions to the drugs and materials used, were reported. Both CO and SSD could heal the burn wounds at 10 days of treatment. However, CO significantly shortened the time of wound necrotic tissue removal by 5 days. Trial Registration: ChiCTR2100046971.

Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma.

BACKGROUND: The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma (HCC), and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than monotherapy. However, the mechanisms underlying this innovative treatment modality have not been elucidated. AIM: To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX in patients with unresectable HCC. METHODS: We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy, immunotherapy, and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen. RESULTS: The objective response rate was 60.4% (32/53), complete response was 24.5% (13/53), partial response was 35.9% (19/53), and stable disease was 39.6% (21/53). The median duration of response and median progression-free survival were 9.1 and 13.9 months, respectively. The surgical conversion rate was 34.0% (18/53), and 1-year overall survival was 83.0% without critical complicating diseases or adverse events (AEs). CONCLUSION: The regimen of HAIC of FOLFOX, targeted therapy, and immunotherapy was curative for patients with unresectable HCC, with no serious AEs and a high rate of surgical conversion.

Formulation and Characterization of Ethosomes for Transdermal Delivery of Prinsepia Utilis Rogle Seed Oil with Ameliorative Effects against UVB-Induced Skin Damage.

Prinsepia utilis seed oil (PUSO) is a natural medication obtained from Prinsepia utilis Rogle seed, which has been used for the treatment of skin diseases. The study aims to prepare ethosomes with high drug loading as a water-soluble transdermal vehicle to enhance the transdermal delivery of PUSO. PUSO-loaded ethosomes (PEs) were prepared using a cold method, and optimized by an orthogonal experimental design with entrapment efficiency (EE) as the dependent variable. The PEs prepared with the optimized formulation showed good stability, with a spherical shape under transmission electron microscopy (TEM), average particle size of 39.12 ± 0.85 nm, PDI of 0.270 ± 0.01, zeta potential of -11.3 ± 0.24 mV, and EE of 95.93 ± 0.43%. PEs significantly increased the skin deposition of PUSO compared to the PUSO suspension (P < 0.001). Moreover, the optimum formula showed significant ameliorative effects on ultraviolet B (UVB) irradiation-associated macroscopic and histopathological changes in mice skin. Therefore, PEs represent a promising therapeutic approach for the treatment of UVB-induced skin inflammation, with the potential for industrialization.

High-Speed and High-Responsivity Blue Light Photodetector with an InGaN NR/PEDOT:PSS Heterojunction Decorated with Ag NWs.

InGaN nanorods possessing larger and wavelength selective absorption by regulating In component based visible light photodetectors (PDs) as one of the key components in the field of visible light communication have received widespread attention. Currently, the weak photoelectric conversion efficiency and slow photoresponse speed of InGaN nanorod (NR) based PDs due to high surface states of InGaN NRs impede the actualization of high-responsivity and high-speed blue light PDs. Here, we have demonstrated high-performance InGaN NR/PEDOT:PSS@Ag nanowire (NW) heterojunction blue light photodetectors utilizing surface passivation and a localized surface plasmon resonance effect. The dark current is significantly reduced by passivating the InGaN NR surface states using PEDOT:PSS. The photoelectric conversion efficiency is significantly increased by increasing light absorption due to the electromagnetic field oscillation of Ag NWs. The responsivity, external quantum efficiency, detectivity, and fall/off time of the InGaN NR/PEDOT:PSS@Ag NW PDs are up to 2.9 A/W, 856%, 6.64 × 1010 Jones, and 439/725 µs, respectively, under 1 V bias and 420 nm illumination. The proposed device design presents a novel approach toward the development of low-cost, high-responsivity, high-speed blue light photodetectors for applications involving visible light communication.

Bitter taste TAS2R14 activation by intracellular tastants and cholesterol.

Bitter taste receptors, particularly TAS2R14, play central roles in discerning a wide array of bitter substances, ranging from dietary components to pharmaceutical agents1,2. TAS2R14 is also widely expressed in extragustatory tissues, suggesting its extra roles in diverse physiological processes and potential therapeutic applications3. Here we present cryogenic electron microscopy structures of TAS2R14 in complex with aristolochic acid, flufenamic acid and compound 28.1, coupling with different G-protein subtypes. Uniquely, a cholesterol molecule is observed occupying what is typically an orthosteric site in class A G-protein-coupled receptors. The three potent agonists bind, individually, to the intracellular pockets, suggesting a distinct activation mechanism for this receptor. Comprehensive structural analysis, combined with mutagenesis and molecular dynamic simulation studies, elucidate the broad-spectrum ligand recognition and activation of the receptor by means of intricate multiple ligand-binding sites. Our study also uncovers the specific coupling modes of TAS2R14 with gustducin and Gi1 proteins. These findings should be instrumental in advancing knowledge of bitter taste perception and its broader implications in sensory biology and drug discovery.

Illuminating the Characteristics and Assembly of Prokaryotic Communities across a pH Gradient in Pit Muds for the Production of Chinese Strong-Flavor Baijiu.

Pit mud (PM), as an important source of microorganisms, is necessary for Chinese strong-flavor baijiu (CSFB) production. Although it has been revealed that the PM prokaryotic community diversities are influenced by its quality, product area, ages, etc., the characteristics and assembly process of the prokaryotic community in PMs across a pH gradient are still unclear. In this study, the regular changes of α- and ß-diversities of the prokaryotic community across a pH gradient in PMs were revealed, which could be divided into "stable", "relatively stable", and "drastically changed" periods. A total of 27 phyla, 53 classes, and 381 genera were observed in all given samples, dominated by Firmicutes, Bacteroidetes, Proteobacteria, Lactobacillus, Caproiciproducens, Proteiniphilum, etc. Meanwhile, the complexity of the network structure of the prokaryotic microbial communities is significantly influenced by pH. The community assembly was jointly shaped by deterministic and stochastic processes, with stochastic process contributing more. This study was a specialized report on elucidating the characteristics and assembly of PM prokaryotic communities across a pH gradient, and revealed that the diversity and structure of PM prokaryotic communities could be predictable, to some degree, which could contribute to expanding our understanding of prokaryotic communities in PM.

Environmental concentrations of microplastic-induced gut microbiota and metabolite disruption in silkworm, Bombyx mori.

Microplastics (MPs) existing extensively in various ecosystems can be ingested by marine organisms and enter the food chain, resulting the health risks from the presence of MPs in aquatic and terrestrial ecosystems. In the present study, an ideal model for Lepidoptera, the silkworm, Bombyx mori, was exposed to environmental concentrations (0.125 µg, 0.25 µg or 0.5 µg/diet) of MPs for 5 days, and the global changes in gut microbes and metabolites were subsequently examined via 16S rDNA sequencing and GC‒MS-based metabolomics. The results showed that MPs exposure did not seriously threaten survival but may regulate signaling pathways involved in development and cocoon production. MPs exposure induced gut microbiota perturbation according to the indices of α-diversity and ß-diversity, and the functional prediction of the altered microbiome and associated metabolites demonstrated the potential roles of the altered microbiome following MPs exposure in the metabolic and physiological states of silkworm. The metabolites markedly altered following MPs exposure may play vital biological roles in energy metabolism, lipid metabolism, xenobiotic detoxification and the immune system by directly or indirectly affecting the physiological state of silkworms. These findings contribute to assessing the health risks of MPs exposure in model insects and provide novel insight into the toxicity mechanism of MPs.

Effects of Tibetan medicine Longdan zhike tablet on chronic obstructive pulmonary disease through MAPK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Longdan zhike tablet (LDZK) is a Tibetan medicine formula commonly used in the highland region of Tibet, China, to ameliorate respiratory diseases, such as acute bronchitis and asthma. In Chinese traditional medicine, some herbal formulas with anti-inflammatory properties targeting the respiratory system are clinically adopted as supplementary therapies for chronic obstructive pulmonary disease (COPD). However, the specific anti-COPD effects of LDZK remain to be evaluated. AIM OF THE STUDY: The aim of this study is to identify the principal bioactive compounds in LDZK, and elucidate the effects and mechanisms of the LDZK on COPD. METHODS: High-resolution mass spectrometry was utilized for a comprehensive characterization of the chemical composition of LDZK. The therapeutic effects of LDZK were assessed on the LPS-papain-induced COPD mouse model, and LPS-induced activation model of A549 cells. The safety of LDZK was evaluated by orally administering a single dose of 30 g/kg to rats and monitoring physiological and biochemical indicators after a 14-day period. Network pharmacology and Western blot analysis were employed for mechanism prediction of LDZK. RESULTS: A comprehensive analysis identified a total of 45 compounds as the major constituents of LDZK. Oral administration of LDZK resulted in notable ameliorative effects in respiratory function, accompanied by reduced inflammatory cell counts and cytokine levels in the lungs of COPD mice. Acute toxicity tests demonstrated a favorable safety profile at a dose equivalent to 292 times the clinically prescribed dose. In vitro studies revealed that LDZK exhibited protective effects on A549 cells by mitigating LPS-induced cellular damage, reducing the release of NO, and downregulating the expression of iNOS, COX2, IL-1ß, IL-6, and TNF-α. Network pharmacology and Western blot analysis indicated that LDZK primarily modulated the MAPK signaling pathway and inhibited the phosphorylation of p38/ERK/JNK. CONCLUSIONS: LDZK exerts significant therapeutic effects on COPD through the regulation of the MAPK pathway, suggesting its potential as a promising adjunctive therapy for the treatment of chronic inflammation in COPD.

Molecular Mechanisms of circRNA-miRNA-mRNA Interactions in the Regulation of Goose Liver Development.

The liver, a crucial metabolic organ in animals, is responsible for the synthesis, breakdown, and transport of lipids. However, the regulatory mechanisms involving both coding and noncoding RNAs that oversee the development of the goose liver remain elusive. This study aimed to fill this knowledge gap by conducting RNA-seq to profile the expression of circular RNAs (circRNAs) and microRNAs (miRNAs) during goose liver development. We analyzed circRNAs in liver samples from Sichuan white geese at three developmental stages: posthatching day 0, 10 weeks (fast growth stage), and 30 weeks (sexual maturation stage). Our findings revealed 11,079 circRNAs and 994 miRNAs, among which the differentially expressed circRNAs and miRNAs were significantly enriched in pathways such as fatty acid biosynthesis, degradation, and metabolism. Further analysis of the target genes of the differentially expressed miRNAs revealed enrichment in pathways related to fatty acid biosynthesis, metabolism, PPAR signaling, DNA replication, and the cell cycle. We also established circRNA-miRNA-mRNA regulatory networks, identifying key regulatory factors and miRNAs. In conclusion, our study offers valuable insights into the complex interplay of circRNA-miRNA-mRNA interactions during goose liver development, and illuminates the molecular pathways that regulate this vital life function.

A novel hybrid modelling framework for GPP estimation: Integrating a multispectral surface reflectance based Vcmax25 simulator into the process-based model.

Terrestrial gross primary productivity (GPP) is the key element in the carbon cycle process. Accurate GPP estimation hinges on the maximum carboxylation rate (Vcmax,025). The high uncertainty in deriving ecosystem-level Vcmax,025 has long hampered efforts toward the performance of the GPP model. Recently studies suggest the strong relationship between spectral reflectance and Vcmax,025. We proposed the multispectral surface reflectance-driven Vcmax,025 simulator using the fully connected deep neural network and built the hybrid modelling framework for GPP estimation by integrating the data-driven Vcmax,025 simulator in the process-based model. The performance of hybrid GPP model was evaluated at 95 flux sites. The result shows that the multispectral surface reflectance-driven Vcmax,025 simulator acquires the satisfactory estimation, with correlation coefficient (R), root mean square error (RMSE) and median absolute percentage error (MdAPE) ranging from 0.34 to 0.80, 14 to 43 µmol m-2 s-1 and 21 % to 66 % across different land cover types, respectively. The hybrid framework generates good GPP estimates with R, RMSE and MdAPE varying from 0.76 to 0.89, 1.79 to 6.16 µmol m-2 s-1 and 27 % to 90 %, respectively. Compared with EVI-driven method, the multispectral surface reflectance significantly improves the Vcmax,025 and GPP estimates, with MdAPE declining by 0.6 %-18 % and 1 % to 21 %, respectively. The Shapley value analysis reveals that red (620-670 nm), near-infrared (841-876 nm) and shortwave infrared (1628-1652 nm and 2105-2155 nm) are the key bands for Vcmax,025 estimation. This study highlights the potential of multispectral surface reflectance for quantifying ecosystem-level Vcmax,025. The new hybrid framework fully extracts the information of all available spectral bands using deep learning to reduce parameter uncertainty while maintains the description of photosynthetic process to ensure its physical reasonability. It can serve as a powerful tool for accurate global GPP estimation.

Endoscopic endonasal transsphenoidal surgery for unusual sellar lesions: eight cases and review of the literature.

Background: Preoperative imaging for some unusual lesions in the sellar region can pose challenges in establishing a definitive diagnosis, impacting treatment strategies. Methods: This study is a retrospective analysis of eight cases involving unusual sellar region lesions, all treated with endoscopic endonasal transsphenoidal surgery (EETS). We present the clinical, endocrine, and radiological characteristics, along with the outcomes of these cases. Results: Among the eight cases, the lesions were identified as follows: Solitary fibrous tumor (SFT) in one case, Lymphocytic hypophysitis (LYH) in one case, Cavernous sinus hemangiomas (CSH) in one case, Ossifying fibroma (OF) in two cases; Sphenoid sinus mucocele (SSM) in one case, Pituitary abscess (PA) in two cases. All patients underwent successful EETS, and their diagnoses were confirmed through pathological examination. Postoperatively, all patients had uneventful recoveries without occurrences of diabetes insipidus or visual impairment. Conclusion: Our study retrospectively analyzed eight unusual lesions of the sellar region. Some lesions exhibit specific imaging characteristics and clinical details that can aid in preoperative diagnosis and inform treatment strategies for these unusual sellar diseases.

Effects of short-term florfenicol exposure on the gene expression pattern, midgut microbiota, and metabolome in the lepidopteran model silkworm (Bombyx mori).

Florfenicol (FF), an alternative veterinary antibiotic for chloramphenicol, has been widely utilized in livestock breeding to prevent and treat bacterial diseases. However, the toxicological effects of FF have yet to be fully disclosed. The domesticated silkworm (Bombyx mori), a lepidopteran model, was selected to assess the toxicological effects of FF dietary exposure with multi-omics. The findings showed that high-dose (250 µg/L) FF exposure increased the whole cocoon weight. High-dose FF exposure affected the species richness and community diversity of the microbiota in the silkworm midgut. Biochemical processes and innate immunity were impacted by FF exposure. The KEGG pathways impacted by the midgut microbiota and their metabolites were compared, and several pathways were found to be related to the two ecosystems. In addition, the innate immunity and lipid metabolism pathways were impacted, and some of the differentially expressed genes were enriched in these pathways. These related pathways may involve crosstalk between the midgut microbiota shift, midgut biological functions, and global gene expression. Therefore, our study also advances the application of the silkworm larval model in assessing antibiotic metabolic toxicity and provides novel insights into the potential risks of FF.

Kaempferol-3-O-sophoroside (PCS-1) contributes to modulation of depressive-like behaviour in C57BL/6J mice by activating AMPK.

BACKGROUND AND PURPOSE: Kaempferol-3-O-sophoroside (PCS-1) is the main component in Crocus sativus (Saffron), a herb with mood-enhancing properties. AMP-activated protein kinase (AMPK) is a potential therapeutic target for depression. This study explores the antidepressive-like properties of PCS-1 and its AMPK activation to confirm AMPK as a target for antidepression. EXPERIMENTAL APPROACH: Corticosterone (CORT)-induced PC12 cell injury served as an in vitro model to evaluate the neuroprotective effect of PCS-1. Neuro-2a cells and primary neurons were utilized to evaluate the synaptogenesis role of PCS-1. CORT-induced mouse depression model and chronic unpredictable mild stress (CUMS) model were used to assess the antidepressive-like properties of PCS-1 through behavioural tests, magnetic resonance imaging, and biochemical index measurements. Western blot and immunofluorescence assays were used to study the mechanisms of PCS-1. Cellular thermal shift assay was used to confirm the binding target. KEY RESULTS: PCS-1 (12.5-50 µM) ameliorated CORT-induced PC12 cell damage, oxidative stress and inflammation. PCS-1 alone promoted an increase in synapses in Neuro-2a cells and primary neurons. Oral administration of PCS-1 (10 and 20 mg·kg-1 ) ameliorated weight loss, dyskinesia, and hippocampal volume reduction induced by CORT and CUMS. PCS-1 bound to AMPK to improve the expression of brain-derived neurotrophic factor (BDNF) and induce autophagy. CONCLUSION AND IMPLICATIONS: PCS-1 binds to AMPK to promote BDNF production and autophagy enhancement, ultimately achieving antidepressant effects. This study provides support for the clinical application of saffron petals and provides further evidence for AMPK as a potential target for antidepression.

Association of red blood cell distribution width and hemoglobin-to-RDW ratio with contrast-associated acute kidney injury in patients undergoing coronary angiography: A retrospective study.

BACKGROUND: Inflammation contributes to poor prognosis in cardiovascular diseases. A novel biomarker for systemic inflammation that has garnered attention is the red blood cell distribution width (RDW). This study is designed to explore potential associations between RDW and hemoglobin-to-RDW ratio (HRR) with contrast-associated acute kidney injury (CA-AKI). METHODS: This study retrospectively analyzed 4054 patients undergoing coronary angiography (CAG). Linear regression models were employed to assess the relationships between RDW or HRR and the elevation of serum creatinine (Scr). The associations between RDW or HRR and CA-AKI were explored using restricted cubic spline and log-binomial regression analyses taking into account specific cutoff values and quintiles. Exploratory analyses were also conducted to further investigate these associations. RESULTS: Among enrolled patients, the average age was 66.9 years and 34.3% were female. Notably, patients who developed CA-AKI tended to have higher RDW and lower HRR. Multivariable linear regression models demonstrated that RDW exhibited a positive association with Scr elevation (ß = 2.496, 95% confidence interval [CI] = 1.784-3.208), while HRR displayed a negative association (ß = -3.559, 95% CI = -4.243 to -2.875). Multivariable log-binomial regression models confirmed that both high RDW (RDW ≥ 13.8%) and low HRR (HRR < 8.9) were significantly associated with a higher risk of CA-AKI (RDW [≥13.8% vs. <13.8%]: relative risk [RR] = 1.540, 95% CI = 1.345-1.762; HRR [<8.9 vs. ≥8.9]: RR = 1.822, 95% CI = 1.584-2.096). Exploratory analysis determined that such associations still existed regardless of age, gender, estimated glomerular filtration rate, or anemia. CONCLUSIONS: Elevated preoperative RDW and decreased HRR were significantly associated with CA-AKI in patients undergoing CAG.