Central Nervous System Disturbances by Thiamethoxam in Japanese Quail (Coturnix japonica): In Vivo, ex Vivo, and in Silico Study.

The neurotoxic effects of neonicotinoids (NEOs) have been widely reported in relation to the poisoning of wild birds, yet the underlying molecular mechanism has remained elusive. This study employed Japanese quails (Coturnix japonica) and primary quail embryonic neurons as in vivo and ex vivo models, respectively, to investigate the neurotoxic effects and mechanism of thiamethoxam (TMX), a representative neonicotinoid insecticide, at environmentally relevant concentrations. Following a 28-day exposure to TMX, metabolomic analysis of quail brain revealed TMX-induced changes in glutamatergic, GABA-ergic, and dopaminergic function. Subsequent ex vivo and in silico experimentation revealed that the activation of nicotinic acetylcholine receptors and calcium signaling, induced by clothianidin (CLO), the primary metabolite of TMX, served as upstream events for the alterations in neurotransmitter synthesis, metabolism, release, and uptake. Our findings propose that the disruption of the central nervous system, caused by environmentally significant concentrations of NEOs, may account for the avian poisoning events induced by NEOs.

PdMoPtCoNi High Entropy Nanoalloy with d Electron Self-Complementation-Induced Multisite Synergistic Effect for Efficient Nanozyme Catalysis.

Engineering multimetallic nanocatalysts with the entropy-mediated strategy to reduce reaction activation energy is regarded as an innovative and effective approach to facilitate efficient heterogeneous catalysis. Accordingly, conformational entropy-driven high-entropy alloys (HEAs) are emerging as a promising candidate to settle the catalytic efficiency limitations of nanozymes, attributed to their versatile active site compositions and synergistic effects. As proof of the high-entropy nanozymes (HEzymes) concept, elaborate PdMoPtCoNi HEA nanowires (NWs) with abundant active sites and tuned electronic structures, exhibiting peroxidase-mimicking activity comparable to that of natural horseradish peroxidase are reported. Density functional theory calculations demonstrate that the enhanced electron abundance of HEA NWs near the Fermi level (EF) is facilitated via the self-complementation effect among the diverse transition metal sites, thereby boosting the electron transfer efficiency at the catalytic interface through the cocktail effect. Subsequently, the HEzymes are integrated with a portable electronic device that utilizes Internet of Things-driven signal conversion and wireless transmission functions for point-of-care diagnosis to validate their applicability in digital biosensing of urinary biomarkers. The proposed HEzymes underscore significant potential in enhancing nanozymes catalysis through tunable electronic structures and synergistic effects, paving the way for reformative advancements in nano-bio analysis.

HcGr76 responds to fructose and chlorogenic acid and is involved in regulation of peptide expression in the midgut of Hyphantria cunea larvae.

BACKGROUND: Sensing dietary components in the gut is important to ensure an appropriate hormonal response and metabolic regulation after food intake. The fall webworm, Hyphantria cunea, is a major invasive pest in China and has led to significant economic losses and ecosystem disruption. The larvae's broad host range and voracious appetite for leaves make H. cunea a primary cause of serious damage to both forests and crops. To date, however, the gustatory receptors (Grs) of H. cunea and their regulatory function remain largely unknown. RESULTS: We identified the fall webworm gustatory receptor HcGr76 as a fructose and chlorogenic acid receptor using Ca2+ imaging and determination of intracellular Ca2+ concentration by a microplate reader. Moreover, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis revealed that HcGr76 is highly expressed in the anterior and middle midgut. Knockdown of HcGr76 caused a significant reduction in the expression of neuropeptide F 1 (NPF1) and CCHamide-2, and led to a decrease in carbohydrate and lipid levels in the hemolymph. CONCLUSION: Our studies provide circumstantial evidence that HcGr76 expressed in the midgut is involved in sensing dietary components, and regulates the expression of relevant peptide hormones to alter metabolism in H. cunea larvae, thus providing a promising molecular target for the development of new insect-specific control products. © 2024 Society of Chemical Industry.

Red Blood Cell Distribution Width Predicts Mortality in Hospitalized Patients with Severe Fever with Thrombocytopenia Syndrome.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging epidemic infectious disease with high mortality rate. This study aimed to investigate the association of red blood cell distribution width (RDW) and mortality risk in hospitalized SFTS patients. Methods: Clinical data of SFTS patients was retrospectively collected from three hospitals between October 2010 and August 2022. Cox proportional hazards model was used to identity the risk factors for fatal outcome. The predictive value of RDW for fatal outcome was evaluated by the receiver operating characteristic (ROC) analysis and Kaplan-Meier methods. Results: Of 292 patients, the median age was 61.5 years. Non-survivors showed higher RDW value than survivors (13.6% vs.13.0%, P < 0.001). The mortality rate was 44.8% in patients with elevated RDW compared to 18.4% of patients with normal RDW, with a relative risk (RR) of 2.439. Elevated RDW was an independent risk factor of mortality (hazards ratio: 1.167, P = 0.019). Patients with elevated RDW had a higher cumulative mortality than patients with normal RDW. The area under the ROC curve (AUC) of RDW for the prediction of mortality was 0.690 (P < 0.001). Conclusion: Elevated RDW was associated with higher mortality risk for patients hospitalized for SFTS. RDW may be helpful for risk stratification in SFTS patients.

Integrated self-assembly and cross-linking technology engineered photodynamic antimicrobial film for efficient preservation of perishable foods.

A new antibacterial film was constructed to combat the severe spoilage of fruits and vegetables caused by microorganisms. Specifically, photoresponsive cinnamaldehyde-tannic­iron acetate nanospheres (CTF NPs) were prepared using ultrasonic-triggered irreversible equilibrium self-assembly and ionic cross-linking co-driven processes and were integrated into the matrix of κ-carrageenan (KC) (CTF-KC films) as functional fillers. The CTF0.4-KC film (KC film doped with 0.4 mg/mL CTF NPs) showed a 99.99% bactericidal rate against both E. coli and S. aureus, extended the storage period of cherry tomatoes from 20 to 32 days. The introduction of CTF enhanced the barrier, thermal stability, and mechanical strength properties, albeit with a slight compromise on transparency. Furthermore, the biosafety of the CTF0.4-KC film was confirmed through hemolysis and cytotoxicity tests. Together, the aforementioned results demonstrated the outstanding antibacterial and fresh-keeping properties of CTF0.4-KC. These desirable properties highlight the potential use of CTF0.4-KC films in food preservation applications.

Lower HBV DNA level is associated with more severe liver fibrosis in HBeAg-positive chronic hepatitis B with normal alanine transaminase.

BACKGROUND: The association of hepatitis B virus (HBV) DNA levels and liver fibrosis in chronic hepatitis B (CHB) patients with immune-tolerant phase remains unclear. We explored the association between liver fibrosis and HBV DNA levels in HBeAg-positive CHB patients with normal alanine transaminase (ALT) with relatively high HBV DNA. METHODS: Six hundred and twenty-two HBeAg-positive CHB patients with normal ALT were included. Patients were divided into three categories: low (6 log10 IU/mL ≤ HBV DNA < 7 log10 IU/mL), moderate (7 log10 IU/mL ≤ HBV DNA < 8 log10 IU/mL), and high (HBV DNA ≥ 8 log10 IU/mL). APRI, FIB-4, transient elastography, or liver biopsy were used to assess liver fibrosis. RESULTS: The median age of patients was 33.0 years and 57.9% patients were male. 18.8%, 52.1%, and 29.1% of patients had low, moderate, and high HBV DNA levels, respectively. The APRI (0.33 vs. 0.26 vs. 0.26, P < 0.001), FIB-4 (1.03 vs. 0.71 vs. 0.68, P < 0.001), and LSM values (7.6 kPa vs. 5.6 kPa vs. 5.5 kPa, P = 0.086) were higher in low HBV DNA group than other two groups. Low HBV DNA group had higher proportions of significant fibrosis (24.8% vs. 9.9% vs. 3.3%, P < 0.001) and cirrhosis (7.7% vs. 2.5% vs. 1.1%, P = 0.004) than moderate and high HBV DNA groups. Moderate (OR 3.095, P = 0.023) and low (OR 4.968, P = 0.003) HBV DNA were independent risk factors of significant fibrosis. CONCLUSION: Lower HBV DNA level was associated with more severe liver fibrosis in HBeAg-positive CHB patients with ALT.

Delta-radiomics Analysis Based on Multi-phase Contrast-enhanced MRI to Predict Early Recurrence in Hepatocellular Carcinoma After Percutaneous Thermal Ablation.

RATIONALE AND OBJECTIVES: It is critical to predict early recurrence (ER) after percutaneous thermal ablation (PTA) for hepatocellular carcinoma (HCC). We aimed to develop and validate a delta-radiomics nomogram based on multi-phase contrast-enhanced magnetic resonance imaging (MRI) to preoperatively predict ER of HCC after PTA. MATERIALS AND METHODS: We retrospectively enrolled 164 patients with HCC and divided them into training, temporal validation, and other-scanner validation cohorts (n = 110, 29, and 25, respectively). The volumes of interest of the intratumoral and/or peritumoral regions were delineated on preoperative multi-phase MR images. Original radiomics features were extracted from each phase, and delta-radiomics features were calculated. Logistic regression was used to train the corresponding radiomics models. The clinical and radiological characteristics were evaluated and combined to establish a clinical-radiological model. A fusion model comprising the best radiomics scores and clinical-radiological risk factors was constructed and presented as a nomogram. The performance of each model was evaluated and recurrence-free survival (RFS) was assessed. RESULTS: Child-Pugh grade B, high-risk tumor location, and an incomplete/absent tumor capsule were independent predictors of ER. The optimal radiomics model comprised 12 delta-radiomics features with areas under the curve (AUCs) of 0.834, 0.795, and 0.769 in the training, temporal validation, and other-scanner validation cohorts, respectively. The nomogram showed the best predictive performance with AUCs as 0.893, 0.854, and 0.827 in the three datasets. There was a statistically significant difference in RFS between the risk groups calculated using the delta-radiomics model and nomogram. CONCLUSIONS: The nomogram combined with the delta-radiomic score and clinical-radiological risk factors could non-invasively predict ER of HCC after PTA.

Lead specifically declines tyrosine hydroxylase activity to induce the onset of Parkinson's disease through disrupting dopamine biosynthesis in fly models.

Parkinson's disease (PD) is one of the fastest-growing neurodegenerative diseases and has been linked to the exposure to numerous environmental neurotoxins. Although lead (Pb) exposure has been related to the development of PD, the molecular target of Pb to cause the onset of PD is insufficiently investigated. Herein, we explored the effects of Pb exposure on behavior, pathophysiology, and gene expression of wild-type (WT) fly (Drosophila melanogaster) by comparison with its PD model. After exposure to Pb, the WT flies showed PD-like locomotor impairments and selective loss of dopaminergic (DAergic) neurons, displaying similar phenotypes to fly PD model (PINK1). Transcriptomic analysis showed the similarity in gene expression profiles between Pb treatment WT flies and PINK1 mutant flies. Moreover, Pb exposure resulted in endogenous dopamine deficits in WT flies. Analyses of gene expression and enzyme activity confirmed that Pb exposure reduced tyrosine hydroxylase (TH) activity and led to failure of dopamine synthesis. Furthermore, molecular dynamics simulation confirmed that Pb was adsorbed by TH and subsequently inhibited the enzymatic activity. Exogenous injection of L-dopa and melatonin could partially rescue the pathological phenotypes of Pb-exposed flies and PD fly model. Antagonist injection of microRNA-133, which negatively regulated the expression of TH gene, ultimately rescued in the manifestation of PD phenotypes in flies. Involvement of TH overexpression mutants of fly strongly promoted the resistance to Pb exposure and rescued both behavior and the number of DAergic neurons. Therefore, our study elucidates the Pb molecular target in dopamine pathway and mechanism underlying the risks of Pb exposure on the occurrence of PD at environmentally-relevant concentrations.

A novel zwitterionic magnetic nanocomposite developed for non-invasive speciation analysis of inorganic chromium.

3-(2-Aminoethylamino)propyltriethoxysilane and carboxyethylsilanetriol sodium salt were grafted on silica-coated Fe3O4 nanoparticles via sol-gel process to prepare novel amine- and carboxyl-bifunctionalized magnetic nanocomposites (SMNPs-(NH2 + COOH)). After well characterized, this doubly functionalized material was used as magnetic solid-phase extraction (MSPE) adsorbent to separate and enrich inorganic chromium species followed by inductively coupled plasma-mass spectrometry detection. The optimization of MSPE operation parameters including pH was conducted. It is reasonably elucidated that the adsorption mechanisms of zwitterionic SMNPs-(NH2 + COOH) towards chromium species are electrostatic and/or coordination interactions. Cr(VI) and Cr(III) can be adsorbed around pH 3.0 and around 10.0 respectively with strong anti-interference ability not only from other co-existing ions but also from the two labile species each other, and eluted by dilute nitric acid solution. With a 15-fold enrichment factor, the limits of detection of Cr(VI) and Cr(III) were 0.008 and 0.009 µg L-1, respectively, profiting from the maximum adsorption capacities of 7.52 and 6.11 mg g-1. The just one magnetic extraction matrix based speciation scheme possesses excellent convenience and friendliness to Cr(VI) and Cr(III) without any oxidation or reduction prior to capture of these two species. This protocol has been successfully applied to the speciation analysis of inorganic chromium in real-world environmental water samples.

Adenosine mediates the amelioration of social novelty deficits during rhythmic light treatment of 16p11.2 deletion female mice.

Non-invasive brain stimulation therapy for autism spectrum disorder (ASD) has shown beneficial effects. Recently, we and others demonstrated that visual sensory stimulation using rhythmic 40 Hz light flicker effectively improved cognitive deficits in mouse models of Alzheimer's disease and stroke. However, whether rhythmic visual 40 Hz light flicker stimulation can ameliorate behavioral deficits in ASD remains unknown. Here, we show that 16p11.2 deletion female mice exhibit a strong social novelty deficit, which was ameliorated by treatment with a long-term 40 Hz light stimulation. The elevated power of local-field potential (LFP) in the prefrontal cortex (PFC) of 16p11.2 deletion female mice was also effectively reduced by 40 Hz light treatment. Importantly, the 40 Hz light flicker reversed the excessive excitatory neurotransmission of PFC pyramidal neurons without altering the firing rate and the number of resident PFC neurons. Mechanistically, 40 Hz light flicker evoked adenosine release in the PFC to modulate excessive excitatory neurotransmission of 16p11.2 deletion female mice. Elevated adenosine functioned through its cognate A1 receptor (A1R) to suppress excessive excitatory neurotransmission and to alleviate social novelty deficits. Indeed, either blocking the A1R using a specific antagonist DPCPX or knocking down the A1R in the PFC using a shRNA completely ablated the beneficial effects of 40 Hz light flicker. Thus, this study identified adenosine as a novel neurochemical mediator for ameliorating social novelty deficit by reducing excitatory neurotransmission during 40 Hz light flicker treatment. The 40 Hz light stimulation warrants further development as a non-invasive ASD therapeutics.

A liquid metal-embedded 3D interconnected-porous TPU/MXene composite with improved capacitive sensitivity and pressure detection range.

Flexible capacitive sensors are widely deployed in wearable smart electronics. Substantial studies have been devoted to constructing characteristic material architectures to improve their electromechanical sensing performance by facilitating the change of the electrode layer spacing. However, the air gaps introduced by the designed material architectures are easily squeezed when subjected to high-pressure loads, resulting in a limited increase in sensitivity over a wide range. To overcome this limitation, in this work, we embed the liquid metal (LM) in the internally interconnected porous structure of a flexible composite foam to fabricate a flexible and high-performance capacitive sensor. Different from the conventional conductive elements filled composite, the incompressible feature of the embedded fluidic LM leads to significantly improved mechanical stability of the composite foam to withstand high pressure loadings, resulting in a wider pressure sensing range from 10 Pa to 260 kPa for our capacitive composite sensor. Simultaneously, the metal conductivity and liquid ductility of the embedded LM endow the as-fabricated capacitive sensor with outstanding mechanical flexibility and pressure sensitivity (up to 1.91 kPa-1). Meanwhile, the LM-embedded interconnected-porous thermoplastic polyurethane/MXene composite sensor also shows excellent reliability over 4000 long-period load cycles, and the response times are merely 60 ms and 110 ms for the loading and unloading processes, respectively. To highlight their advantages in various applications, the as-proposed capacitive sensors are demonstrated to detect human movements and monitor biophysical heart-rate signals. It is believed that our finding could extend the material framework of flexible capacitive sensors and offer new possibilities and solutions in the development of the next-generation wearable electronics.

Silencing the fatty acid elongase gene elovl6 induces reprogramming of nutrient metabolism in male Oreochromis niloticus.

Elongation of very long-chain fatty acids protein 6 (ELOVL6) plays a pivotal role in the synthesis of endogenous fatty acids, influencing energy balance and metabolic diseases. The primary objective of this study was to discover the molecular attributes and regulatory roles of ELOVL6 in male Nile tilapia, Oreochromis niloticus. The full-length cDNA of elovl6 was cloned from male Nile tilapia, and was determined to be 2255-bp long, including a 5'-untranslated region of 193 bp, a 3'-untranslated region of 1252 bp, and an open reading frame of 810 bp encoding 269 amino acids. The putative protein had typical features of ELOVL proteins. The transcript levels of elovl6 differed among various tissues and among fish fed with different dietary lipid sources. Knockdown of elovl6 in Nile tilapia using antisense RNA technology resulted in significant alterations in hepatic morphology, long-chain fatty acid synthesis, and fatty acid oxidation, and led to increased fat deposition in the liver and disrupted glucose/lipid metabolism. A comparative transcriptomic analysis (elovl6 knockdown vs. the negative control) identified 5877 differentially expressed genes with significant involvement in key signaling pathways including the peroxisome proliferator-activated receptor signaling pathway, fatty acid degradation, glycolysis/gluconeogenesis, and the insulin signaling pathway, all of which are crucial for lipid and glucose metabolism. qRT-PCR analyses verified the transcript levels of 13 differentially expressed genes within these pathways. Our findings indicate that elovl6 knockdown in male tilapia impedes oleic acid synthesis, culminating in aberrant nutrient metabolism.

Constructing Lysozyme Protective Layer via Conformational Transition for Aqueous Zn Batteries.

The practical applications for aqueous Zn ion batteries (ZIBs) are promising yet still impeded by the severe side reactions on Zn metal. Here, a lysozyme protective layer (LPL) is prepared on Zn metal surface by a simple and facile self-adsorption strategy. The LPL exhibits extremely strong adhesion on Zn metal to provide stable interface during long-term cycling. In addition, the self-adsorption strategy triggered by the hydrophobicity-induced aggregation effect endows the protective layer with a gap-free and compacted morphology which can reject free water for effective side reaction inhibition performance. More importantly, the lysozyme conformation is transformed from α-helix to ß-sheet structure before layer formation, thus abundant functional groups are exposed to interact with Zn2+ for electrical double layer (EDL) modification, desolvation energy decrease, and ion diffusion kinetics acceleration. Consequently, the LPL renders the symmetrical Zn battery with ultra-long cycling performance for more than 1200 h under high Zn depth of discharge (DOD) for 77.7%, and the Zn/Zn0.25V2O5 pouch cell with low N/P ratio of 2.1 at high Zn utilization of 48% for over 300 cycles. This study proposes a facile and low-cost method for constructing a stable protective layer of Zn metal for high Zn utilization aqueous devices.

Anti-Oxidized Self-Assembly of Multilayered F-Mene/MXene/TPU Composite with Improved Environmental Stability and Pressure Sensing Performances.

MXenes, as emerging 2D sensing materials for next-generation electronics, have attracted tremendous attention owing to their extraordinary electrical conductivity, mechanical strength, and flexibility. However, challenges remain due to the weak stability in the oxygen environment and nonnegligible aggregation of layered MXenes, which severely affect the durability and sensing performances of the corresponding MXene-based pressure sensors, respectively. Here, in this work, we propose an easy-to-fabricate self-assembly strategy to prepare multilayered MXene composite films, where the first layer MXene is hydrogen-bond self-assembled on the electrospun thermoplastic urethane (TPU) fibers surface and the anti-oxidized functionalized-MXene (f-MXene) is subsequently adhered on the MXene layer by spontaneous electrostatic attraction. Remarkably, the f-MXene surface is functionalized with silanization reagents to form a hydrophobic protective layer, thus preventing the oxidation of the MXene-based pressure sensor during service. Simultaneously, the electrostatic self-assembled MXene and f-MXene successfully avoid the invalid stacking of MXene, leading to an improved pressure sensitivity. Moreover, the adopted electrospinning method can facilitate cyclic self-assembly and the formation of a hierarchical micro-nano porous structure of the multilayered f-MXene/MXene/TPU (M-fM2T) composite. The gradient pores can generate changes in the conductive pathways within a wide loading range, broadening the pressure detection range of the as-proposed multilayered f-MXene/MXene/TPU piezoresistive sensor (M-fM2TPS). Experimentally, these novel features endow our M-fM2TPS with an outstanding maximum sensitivity of 40.31 kPa-1 and an extensive sensing range of up to 120 kPa. Additionally, our M-fM2TPS exhibits excellent anti-oxidized properties for environmental stability and mechanical reliability for long-term use, which shows only ~0.8% fractional resistance changes after being placed in a natural environment for over 30 days and provides a reproducible loading-unloading pressure measurement for more than 1000 cycles. As a proof of concept, the M-fM2TPS is deployed to monitor human movements and radial artery pulse. Our anti-oxidized self-assembly strategy of multilayered MXene is expected to guide the future investigation of MXene-based advanced sensors with commercial values.

Solar-driven abnormal evaporation of nanoconfined water.

Intrinsic water evaporation demands a high energy input, which limits the efficacy of conventional interfacial solar evaporators. Here, we propose a nanoconfinement strategy altering inherent properties of water for solar-driven water evaporation using a highly uniform composite of vertically aligned Janus carbon nanotubes (CNTs). The water evaporation from the CNT shows the unexpected diameter-dependent evaporation rate, increasing abnormally with decreasing nanochannel diameter. The evaporation rate of CNT10@AAO evaporator thermodynamically exceeds the theoretical limit (1.47 kg m-2 hour-1 under one sun). A hybrid experimental, theoretical, and molecular simulation approach provided fundamental evidence of different nanoconfined water properties. The decreased number of H-bonds and lower interaction energy barrier of water molecules within CNT and formed water clusters may be one of the reasons for the less evaporative energy activating rapid nanoconfined water vaporization.

Association of liver function and prognosis in patients with severe fever with thrombocytopenia syndrome.

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) is an epidemic emerging infectious disease with high mortality rate. We investigated the association between liver injury and clinical outcomes in patients with SFTS. METHODS: A total of 291 hospitalized SFTS patients were retrospectively included. Cox proportional hazards model was adopted to identify risk factors of fatal outcome and Kaplan-Meier curves were used to estimate cumulative risks. RESULTS: 60.1% of patients had liver injury at admission, and the median alanine transaminase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) levels were 76.4 U/L, 152.3 U/L, 69.8 U/L and 9.9 µmol/L, respectively. Compared to survivors, non-survivors had higher levels of AST (253.0 U/L vs. 131.1 U/L, P < 0.001) and ALP (86.2 U/L vs. 67.9 U/L, P = 0.006), higher proportion of elevated ALP (20.0% vs. 4.4%, P < 0.001) and liver injury (78.5% vs. 54.9%, P = 0.001) at admission. The presence of liver injury (HR 2.049, P = 0.033) at admission was an independent risk factor of fatal outcome. CONCLUSIONS: Liver injury was a common complication and was strongly associated with poor prognosis in SFTS patients. Liver function indicators should be closely monitored for SFTS patients.

Clinical outcomes of treatment-naïve HBeAg-negative patients with chronic hepatitis B virus infection with low serum HBsAg and undetectable HBV DNA.

Serum hepatitis B surface antigen (HBsAg) level < 100 IU/ml and undetectable hepatitis B virus (HBV) DNA have been recently proposed as an alternate endpoint of "partial cure" in chronic hepatitis B (CHB). We investigated clinical outcomes of hepatitis B e antigen (HBeAg)-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA. Treatment-naïve HBeAg-negative CHB patients with undetectable HBV DNA and normal alanine aminotransferase were retrospectively included from three institutions. Patients were classified into the low HBsAg group (<100 IU/ml) and the high HBsAg group (≥100 IU/ml). Liver fibrosis was evaluated by noninvasive tests (NITs). A total of 1218 patients were included and the median age was 41.5 years. Patients with low HBsAg were older (45.0 vs. 40.0 years, P < 0.001) than those in the high HBsAg group, while the NIT parameters were comparable between groups. During a median follow-up of 25.7 months, patients with low HBsAg achieved a higher HBsAg clearance rate (13.0% vs. 0%, P < 0.001) and a lower rate of significant fibrosis development (2.2% vs. 7.0%, P = 0.049) compared to patients with high HBsAg. No patient developed HCC in either group. HBsAg level was negatively associated with HBsAg clearance (HR 0.213, P < 0.001) and patients with HBsAg < 100 IU/ml had a low risk of significant fibrosis development (HR 0.010, P = 0.002). The optimal cutoff value of HBsAg for predicting HBsAg clearance was 1.1 Log10 IU/ml. Treatment-naïve HBeAg-negative CHB patients with HBsAg <100 IU/ml and undetectable HBV DNA had favourable outcomes with a high rate of HBsAg clearance and a low risk of fibrosis progression.

Prevalence, toxin-genotype distribution, and transmission of Clostridium perfringens from the breeding and milking process of dairy farms.

This study aimed to elucidate the distribution, transmission, and cross-contamination of Clostridium perfringens during the breeding and milking process from dairy farms. The prevalence of 22.3% (301/1351) yielded 494 C. perfringens isolates; all isolates were type A, except for one type D, and 69.8% (345/494) of the isolates carried atyp. cpb2 and only 0.6% (3/494) of the isolates carried cons. cpb2. C. perfringens detected throughout the whole process but without type F. 150 isolates were classified into 94 pulsed-field gel electrophoresis (PFGE) genotypes; among them, six clusters contained 34 PFGE genotypes with 58.0% isolates which revealed epidemic correlation and genetic diversity; four PFGE genotypes (PT57, PT9, PT61, and PT8) were the predominant genotypes. The isolates from different farms demonstrated high homology. Our study confirmed that C. perfringens demonstrated broad cross-contamination from nipples and hides of dairy cattle, followed by personnel and tools and air-introduced raw milk during the milking process. In conclusion, raw milk could serve as a medium for the transmission of C. perfringens, which could result in human food poisoning. Monitoring and controlling several points of cross-contamination during the milking process are essential as is implementing stringent hygiene measures to prevent further spread and reduce the risk of C. perfringens infection.

A novel NIR fluorescent probe inhibits melanoma progression through apoptosis and ERK/DRP1-mediated mitochondrial fission.

Melanoma, a highly metastatic malignant tumour, necessitated early detection and intervention. This study focuses on a hemicyanine fluorescent probe activated by near-infrared (NIR) light for bioimaging and targeted mitochondrial action in melanoma cells. IR-418, our newly designed hemicyanine-based NIR fluorescent probe, demonstrated effective targeting of melanoma cell mitochondria for NIR imaging. In vitro and in vivo experiments revealed IR-418's inhibition of melanoma growth through the promotion of mitochondrial apoptosis (Bax/Bcl-2/Cleaved Caspase pathway). Moreover, IR-418 inhibited melanoma metastasis by inhibiting mitochondrial fission through the ERK/DRP1 pathway. Notably, IR-418 mitigated abnormal ATL and ASL elevations caused by tumours without inflicting significant organ damage, indicating its high biocompatibility. In conclusion, IR-418, a novel hemicyanine-based NIR fluorescent probe targeting the mitochondria, exhibits significant fluorescence imaging capability, anti-melanoma proliferation, anti-melanoma lung metastasis activities and high biosafety. Therefore, it has significant potential in the early diagnosis and treatment of melanoma.