A single-dose, randomized, open-label, four-period, crossover equivalence trial comparing the clinical similarity of the proposed biosimilar rupatadine fumarate to reference Wystamm® in healthy Chinese subjects.

Purpose: The aim of this study was to evaluate the bioequivalence of two formulations of rupatadine (10-mg tablets) under fasting and fed conditions in healthy Chinese subjects. Methods: A total of 72 subjects were randomly assigned to the fasting cohort (n = 36) and fed cohort (n = 36). Each cohort includes four single-dose observation periods and 7-day washout intervals. Blood samples were collected at several timepoints for up to 72 h post-dose. The plasma concentration of rupatadine and the major active metabolites (desloratadine and 3-hydroxydesloratadine) were analyzed by a validated HPLC-MS/MS method. The non-compartmental analysis method was employed to determine the pharmacokinetic parameters. Based on the within-subject standard deviation of the reference formulation, a reference-scaled average bioequivalence or average bioequivalence method was used to evaluate the bioequivalence of the two formulations. Results: For the fasting status, the reference-scaled average bioequivalence method was used to evaluate the bioequivalence of the maximum observed rupatadine concentration (Cmax; subject standard deviation > 0.294), while the average bioequivalence method was used to evaluate the bioequivalence of the area under the rupatadine concentration-time curve from time 0 to the last detectable concentration (AUC0-t) and from time 0 to infinity (AUC0-∞). The geometric mean ratio (GMR) of the test/reference for Cmax was 95.91%, and the upper bound of the 95% confidence interval was 95.91%. For AUC0-t and AUC0-∞ comparisons, the GMR and 90% confidence interval (CI) were 98.76% (93.88%-103.90%) and 98.71% (93.93%-103.75%), respectively. For the fed status, the subject standard deviation values of Cmax, AUC0-t, and AUC0-∞ were all <0.294; therefore, the average bioequivalence method was used. The GMR and 90% CI for Cmax, AUC0-t, and AUC0-∞ were 101.19% (91.64%-111.74%), 98.80% (94.47%-103.33%), and 98.63% (94.42%-103.03%), respectively. The two-sided 90% CI of the GMR for primary pharmacokinetic endpoints of desloratadine and 3-hydroxydesloratadine was also within 80%-125% for each cohort. These results met the bioequivalence criteria for highly variable drugs. All adverse events (AEs) were mild and transient. Conclusion: The test drug rupatadine fumarate showed a similar safety profile to the reference drug Wystamm® (J. Uriach y Compañía, S.A., Spain), and its pharmacokinetic bioequivalence was confirmed in healthy Chinese subjects based on fasting and postprandial status. Clinical trial registration: http://www.chinadrugtrials.org.cn/index.html, identifier CTR20213217.

Development and validation of a prognostic model for assessing long COVID risk following Omicron wave-a large population-based cohort study.

BACKGROUND: Long coronavirus disease (COVID) after COVID-19 infection is continuously threatening the health of people all over the world. Early prediction of the risk of Long COVID in hospitalized patients will help clinical management of COVID-19, but there is still no reliable and effective prediction model. METHODS: A total of 1905 hospitalized patients with COVID-19 infection were included in this study, and their Long COVID status was followed up 4-8 weeks after discharge. Univariable and multivariable logistic regression analysis were used to determine the risk factors for Long COVID. Patients were randomly divided into a training cohort (70%) and a validation cohort (30%), and factors for constructing the model were screened using Lasso regression in the training cohort. Visualize the Long COVID risk prediction model using nomogram. Evaluate the performance of the model in the training and validation cohort using the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: A total of 657 patients (34.5%) reported that they had symptoms of long COVID. The most common symptoms were fatigue or muscle weakness (16.8%), followed by sleep difficulties (11.1%) and cough (9.5%). The risk prediction nomogram of age, diabetes, chronic kidney disease, vaccination status, procalcitonin, leukocytes, lymphocytes, interleukin-6 and D-dimer were included for early identification of high-risk patients with Long COVID. AUCs of the model in the training cohort and validation cohort are 0.762 and 0.713, respectively, demonstrating relatively high discrimination of the model. The calibration curve further substantiated the proximity of the nomogram's predicted outcomes to the ideal curve, the consistency between the predicted outcomes and the actual outcomes, and the potential benefits for all patients as indicated by DCA. This observation was further validated in the validation cohort. CONCLUSIONS: We established a nomogram model to predict the long COVID risk of hospitalized patients with COVID-19, and proved its relatively good predictive performance. This model is helpful for the clinical management of long COVID.

The safety and feasibility of laparoscopic anatomical left hemihepatectomy along the middle hepatic vein from the head side approach.

Background: Laparoscopic left hemihepatectomy (LLH) is commonly used for benign and malignant left liver lesions. We compared the benefits and drawbacks of LLH from the head side approach (LLHH) with those of conventional laparoscopic left hemihepatectomy (CLLH). This study was conducted to investigate the safety and feasibility of LLHH by comparing it with CLLH. Methods: In this study, 94 patients with tumor or hepatolithiasis who underwent LLHH (n = 39) and CLLH (n = 55) between January 2016 and January 2023 were included. The preoperative features, intraoperative details, and postoperative outcomes were compared between the two groups. Results: For hepatolithiasis, patients who underwent LLHH exhibited shorter operative time (p = 0.035) and less blood loss (p = 0.023) than those who underwent CLLH. However, for tumors, patients undergoing LLHH only showed shorter operative time (p = 0.046) than those undergoing CLLH. Moreover, no statistically significant differences in hospital stay, transfusion, hospital expenses, postoperative white blood cell (WBC) count, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were observed between the two groups (p > 0.05) for tumor or hepatolithiasis. For hepatocellular carcinoma (HCC), no differences in both overall survival (p = 0.532) and disease-free survival (p = 0.274) were observed between the two groups. Conclusion: LLHH is a safe and feasible surgical procedure for tumors or hepatolithiasis of the left liver.

Repeated trans-spinal magnetic stimulation promotes microglial phagocytosis of myelin debris after spinal cord injury through LRP-1.

Spinal cord injury (SCI) is a serious trauma of the central nervous system. The clearance of myelin debris is a critical step in the functional recovery following spinal cord injury (SCI). Recent studies have begun to reveal critical roles for professional phagocytes in the central nervous system, microglia, and their receptors in the control of myelin debris in neurodegenerative disease. Repeated trans-spinal magnetic stimulation (rTSMS) has been demonstrated as a noninvasive SCI treatment that enhances tissue repair and functional recovery. In this study, we investigated the role and molecular mechanism of rTSMS on microglial phagocytosis of myelin debris in a rat SCI model. In our studies, we found that rTSMS significantly promoted the motor function recovery of SCI rats associated with the inhibition the neuroinflammation and glia scar formation. Immunofluorescence results further showed that the rTSMS promotes the clearance of myelin debris by microglia in vivo and in vitro. Additionally, receptor-associated protein (RAP), a Low-density lipoprotein receptor-related protein-1 (LRP-1) inhibitor, could cancel the accelerated microglial phagocytosis of myelin debris after rTSMS in vitro experiments. Simultaneously, Elisa's results and western blotting respectively showed that rTSMS significantly decreased the levels of soluble LRP-1(sLRP-1) and the LRP-1 splicing enzyme of ADAM17. In conclusion, rTSMS could promote the clearance of myelin debris by microglia through LRP-1 to improve the functional recovery of SCI rats.

Large-scale photonic chiplet Taichi empowers 160-TOPS/W artificial general intelligence.

The pursuit of artificial general intelligence (AGI) continuously demands higher computing performance. Despite the superior processing speed and efficiency of integrated photonic circuits, their capacity and scalability are restricted by unavoidable errors, such that only simple tasks and shallow models are realized. To support modern AGIs, we designed Taichi-large-scale photonic chiplets based on an integrated diffractive-interference hybrid design and a general distributed computing architecture that has millions-of-neurons capability with 160-tera-operations per second per watt (TOPS/W) energy efficiency. Taichi experimentally achieved on-chip 1000-category-level classification (testing at 91.89% accuracy in the 1623-category Omniglot dataset) and high-fidelity artificial intelligence-generated content with up to two orders of magnitude of improvement in efficiency. Taichi paves the way for large-scale photonic computing and advanced tasks, further exploiting the flexibility and potential of photonics for modern AGI.

Periodic magnetic modulation enhanced electrochemical analysis for highly sensitive determination of genomic DNA methylation.

DNA methylation aberrations have a strong correlation with cancer in early detection, diagnosis, and prognosis, which make them possible candidate biomarkers. Electrochemical biosensors offer rapid protocols for detecting DNA methylation status with minimal pretreatment of samples. However, the inevitable presence of background current in the time domain, including electrochemical noise and variations, limits the detection performance of these biosensors, especially for low concentration analytes. Here, we propose an ultrasensitive frequency-domain electrochemical analysis strategy to effectively separate the weak signals from background current. To achieve this, we employed periodic magnetic field modulation of magnetic beads (MBs) on and off the electrode surface to generate a periodic electrochemical signal for subsequent frequency-domain analysis. By capturing labeled MBs with as low as 0.5 pg of DNA, we successfully demonstrated a highly sensitive electrochemical method for determination of genome-wide DNA methylation levels. We also validated the effectiveness of this methodology using DNA samples extracted from three types of hepatocellular carcinoma (HCC) cell lines. The results revealed varying genomic methylation levels among different HCC cell lines, indicating the potential application of this approach for early-stage cancer detection in terms of DNA methylation status.

Toxic effects of triclosan on hepatic and intestinal lipid accumulation in zebrafish via regulation of m6A-RNA methylation.

Triclosan (TCS), recognized as an endocrine disruptor, has raised significant concerns due to its widespread use and potential health risks. To explore the impact of TCS on lipid metabolism, both larval and adult zebrafish were subjected to acute and chronic exposure to TCS. Through analyzes of biochemical and physiological markers, as well as Oil Red O (ORO) and hematoxylin and eosin (H&E) staining, our investigation revealed that TCS exposure induced hepatic and intestinal lipid accumulation in larval and adult zebrafish, leading to structural damage and inflammatory responses in these tissues. The strong affinity of TCS with PPARγ and subsequent pathway activation indicate that PPARγ pathway plays a crucial role in TCS-induced lipid buildup. Furthermore, we observed a decrease in m6A-RNA methylation levels in the TCS-treated group, which attributed to the increased activity of the demethylase FTO and concurrent suppression of the methyltransferase METTL3 gene expression by TCS. The alteration in methylation dynamics is identified as a potential underlying mechanism behind TCS-induced lipid accumulation. To address this concern, we explored the impact of folic acid-a methyl donor for m6A-RNA methylation-on lipid accumulation in zebrafish. Remarkably, folic acid administration partially alleviated lipid accumulation by restoring m6A-RNA methylation. This restoration, in turn, contributed to a reduction in inflammatory damage observed in both the liver and intestines. Additionally, folic acid partially mitigates the up-regulation of PPARγ and related genes induced by TCS. These findings carry substantial implications for understanding the adverse effects of environmental pollutants such as TCS. They also emphasize the promising potential of folic acid as a therapeutic intervention to alleviate disturbances in lipid metabolism induced by environmental pollutants.

Photonic neuromorphic architecture for tens-of-task lifelong learning.

Scalable, high-capacity, and low-power computing architecture is the primary assurance for increasingly manifold and large-scale machine learning tasks. Traditional electronic artificial agents by conventional power-hungry processors have faced the issues of energy and scaling walls, hindering them from the sustainable performance improvement and iterative multi-task learning. Referring to another modality of light, photonic computing has been progressively applied in high-efficient neuromorphic systems. Here, we innovate a reconfigurable lifelong-learning optical neural network (L2ONN), for highly-integrated tens-of-task machine intelligence with elaborated algorithm-hardware co-design. Benefiting from the inherent sparsity and parallelism in massive photonic connections, L2ONN learns each single task by adaptively activating sparse photonic neuron connections in the coherent light field, while incrementally acquiring expertise on various tasks by gradually enlarging the activation. The multi-task optical features are parallelly processed by multi-spectrum representations allocated with different wavelengths. Extensive evaluations on free-space and on-chip architectures confirm that for the first time, L2ONN avoided the catastrophic forgetting issue of photonic computing, owning versatile skills on challenging tens-of-tasks (vision classification, voice recognition, medical diagnosis, etc.) with a single model. Particularly, L2ONN achieves more than an order of magnitude higher efficiency than the representative electronic artificial neural networks, and 14× larger capacity than existing optical neural networks while maintaining competitive performance on each individual task. The proposed photonic neuromorphic architecture points out a new form of lifelong learning scheme, permitting terminal/edge AI systems with light-speed efficiency and unprecedented scalability.

TNF and IFNγ-induced cell death requires IRF1 and ELAVL1 to promote CASP8 expression.

TNFα and IFNγ (TNF/IFNγ) synergistically induce caspase-8 activation and cancer cell death. However, the mechanism of IFNγ in promoting TNF-initiated caspase-8 activation in cancer cells is poorly understood. Here, we found that in addition to CASP8, CYLD is transcriptionally upregulated by IFNγ-induced transcription factor IRF1. IRF1-mediated CASP8 and CYLD upregulation additively mediates TNF/IFNγ-induced cancer cell death. Clinically, the expression levels of TNF, IFNγ, CYLD, and CASP8 in melanoma tumors are increased in patients responsive to immune checkpoint blockade (ICB) therapy after anti-PD-1 treatment. Accordingly, our genetic screen revealed that ELAVL1 (HuR) is required for TNF/IFNγ-induced caspase-8 activation. Mechanistically, ELAVL1 binds CASP8 mRNA and extends its stability to sustain caspase-8 expression both in IFNγ-stimulated and in basal conditions. Consequently, ELAVL1 determines death receptors-initiated caspase-8-dependent cell death triggered from stimuli including TNF and TRAIL by regulating basal/stimulated caspase-8 levels. As caspase-8 is a master regulator in cell death and inflammation, these results provide valuable clues for tumor immunotherapy and inflammatory diseases.

Multi-Omics Analysis Reveals the Role of Changes in Platelet Activation Pathways in the Survival Outcome of Patients with Esophageal Squamous Cell Carcinoma.

Objective: The objective of this study was to integrate metabolomics and transcriptomics data to identify key diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC). Plasma samples were collected from 85 ESCC patients at different stages and 50 healthy volunteers for non-targeted metabolomic analysis. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for non-targeted metabolomic analysis. Subsequently, we integrated the metabolomic data with transcriptomic data from the Gene Expression Omnibus (GEO) and prognosis data from The Cancer Genome Atlas Program (TCGA) to perform pathway analysis. Our focus was on pathways that involve both metabolites and upstream genes, as they often exhibit higher accuracy. Results: Through the integration of metabolomics and transcriptomics, we identified significant alterations in the platelet activation pathway in ESCC. This pathway involves the participation of both metabolites and genes, making it a more accurate reflection of pathological changes associated with the disease. Notably, metabolite arachidonic acid (AA) and chemokine receptor type 2(CXCR2) were significantly downregulated in ESCC, while genes collagen type I alpha 1(COL1A1), collagen type I alpha 2(COL1A2), collagen type III alpha 1(COL3A1), type 3 inositol 1,4,5-trisphosphate receptor (ITPR3), and insulin-like growth factor II mRNA binding protein 3(IGF2BP3) were significantly upregulated, indicating the presence of tumor-induced platelet activation in ESCC. Further analysis of prognosis data revealed that high expression of COL1A1, IGF2BP3, and ITPR3 was associated with a favorable prognosis for ESCC, while high CXCR2 expression was linked to an adverse prognosis. In addition, we combined COL1A1, ITPR3, IGF2BP3, CXCR2, and AA to form a diagnostic biomarker panel. The receiver operating characteristic curve (ROC) demonstrated excellent diagnostic capability (AUC=0.987). Conclusion: Our study underscores the significant role of platelet activation pathways and related genes in the diagnosis and prognosis of ESCC patients. These findings offer promising insights for improving the clinical management of ESCC.

Chronic exposure to low levels of phenanthrene induces histological damage and carcinogenic risk in the uterus of female mice.

Phenanthrene (Phe), a polycyclic aromatic hydrocarbon with low molecular weight, is detected in the environment at high frequency. To study the toxic effects of Phe on the uterine structure and function, female Kunming mice were exposed to Phe (0.05, 0.5, 5 ng/mL) for 270 days by drinking water. Pathological alterations and their action pathways were analyzed using immunohistochemical and biomolecular technology. Phe significantly increased the percentage of blood vessel area, the number of endometrial neutrophils (indicating the occurrence of inflammation), collagen deposition (indicating fibrosis), and the percentage of Ki-67-positive cells (indicating carcinogenesis) in the uterus. Transcriptome sequencing identified differentially expressed genes that were mainly enriched in some signaling pathways, including inflammation and carcinogenesis, suggesting a carcinogenic risk in the Phe-exposed uterus. Elevated serum estrogen levels and decreased progesterone levels exhibited a disturbance of steroid hormone balance, which might be related to uterine damage. Upregulated protein levels of uterine androgen receptor and estrogen receptor α were linked to the pathological effects. Most of the effects exhibited a nonmonotonic dose response, which might be attributed to the corresponding change in the serum levels of Phe. The results suggest that exposure to low levels of Phe could exert adverse effects on the uterus.

Neurotoxic effects of 2-ethylhexyl diphenyl phosphate exposure on zebrafish larvae: Insight into inflammation-driven changes in early motor behavior.

The extensive utilization and potential adverse impacts of the replacement flame-retardant 2-Ethylhexyl Diphenyl Phosphate (EHDPP) have raised concerns. Currently, there is limited knowledge regarding the developmental, neurological, and immunotoxic consequences of EHDPP exposure, as well as its potential behavioral outcomes. In this study, we undertook a comprehensive examination and characterization of the toxic effects over the EHDPP concentration range of 14-1400 nM. Our findings unveiled that EHDPP, even at an environmentally relevant concentration of 14 nM, exhibited excitatory neurotoxicity, eliciting a 13.5 % increase in the swimming speed of zebrafish larvae. This effect might be attributed to the potential influence of EHDPP on the release of neurotransmitters like serotonin and dopamine, which, in turn, mediated anxiety-like behavior in the zebrafish larvae. Conversely, sublethal dose EHDPP (1400 nM) exposure significantly suppressed the swimming vigor of zebrafish larvae, accompanied by morphological changes, abnormal behaviors, and alterations in intracerebral molecules. Transcriptomics revealed the underlying mechanism. The utilization of pathway inhibitors reshaped the inflammatory homeostasis and alleviated the toxicity induced by EHDPP exposure, anchoring the pivotal role played by the TLR4/NF-κB signaling pathway in EHDPP-induced adverse changes in zebrafish behavior and neurophysiology. This study observed the detrimental effects of EHDPP on fish sustainability at environmentally relevant concentrations, highlighting the practical significance for EHDPP risk management. Elucidating the toxic mechanisms of EHDPP will contribute to a deeper comprehension of how environmental pollutants can intricately influence human health.

A New Floating Piezoelectric Microphone for Fully Implantable Cochlear Implants in Middle Ear.

OBJECTIVE: Our team designed a long-lasting, well-sealed microphone, which uses laser welding and vacuum packaging technology. This study examined the sensitivity and effectiveness of this new floating piezoelectric microphone (NFPM) designed for totally implantable cochlear implants (TICIs) in animal experiments and intraoperative testing. METHODS: Different NFPM frequency responses from 0.25 to 10 kHz at 90 dB SPL were analyzed using in vivo testing of cats and human patients. The NFPM was tested in different positions that were clamped to the ossicular chains or placed in the tympanic cavity of cats and human patients. Two volunteers' long incus foot and four cats' malleus neck of the ossicular chain were clamped with the NSFM. The output electrical signals from different locations were recorded, analyzed, and compared. The NFPM was removed after the test without causing any damage to the middle-ear structure of the cats. Intraoperative tests of the NFPM were performed during the cochlear implant surgery and the cochlear implant surgery was completed after all tests. RESULTS: Compared with the results in the tympanic cavity, the NFPM could detect the vibration from the ossicular chain more sensitively in cat experiments and intraoperative testing. We also found that the signal output level of the NFPM decreased as the acoustic stimulation strength decreased in the intraoperative testing. CONCLUSION: The NFPM is effective in the intraoperative testing, making it feasible as an implantable middle-ear microphone for TICIs. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:937-944, 2024.

Heat-shock protein 90 alleviates oxidative stress and reduces apoptosis in liver of Seriola aureovittata (yellowtail kingfish) under high-temperature stress.

Hsp90s are molecular chaperones that enhance fish tolerance to high-temperature stress. However, the function of Hsp90s in Seriola aureovittata (yellowtail kingfish) under high-temperature stress remains largely unknown. Here, two Hsp90 isoforms were identified in S. aureovittata by bioinformatics analysis: SaHsp90α and SaHsp90ß. The coding sequence of SaHsp90α was 2193-bp long and encoded a polypeptide of 730 amino acids; SaHsp90ß was 2178-bp long and encoded a polypeptide of 725 amino acids. SaHsp90α and SaHsp90ß both contained a HATPase domain and a HSP90 domain. Their transcripts were detected in all examined S. aureovittata tissues, with relatively high levels in the gonads, head kidney, and intestine. During high-temperature stress at 28 °C, the expression levels of SaHsp90α and SaHsp90ß transcripts were significantly increased in liver. After simultaneously knocking down the expression of the SaHsp90s, there was a significant decrease in liver superoxide dismutase (SOD) activity and a remarkable increase of malondialdehyde content in liver after high-temperature stress. The expression levels of the key caspase family genes caspase-3 and caspase-7 were also significantly upregulated by high-temperature stress in SaHsp90-knockdown liver. TUNEL labeling demonstrated that the number of apoptotic cells significantly increased in the SaHsp90-knockdown group when high-temperature treatment lasted for 48 h. Protein-protein docking analysis predicted that SaHsp90α and SaHsp90ß can bind to S. aureovittata SOD and survivin, which are key proteins for maintenance of redox homeostasis and inhibition of apoptosis. These findings demonstrate that SaHsp90α and SaHsp90ß play a crucial role in resistance to high-temperature stress by regulating redox homeostasis and apoptosis in yellowtail kingfish.

Real-time fluorescence imaging with indocyanine green during laparoscopic duodenum-preserving pancreatic head resection.

BACKGROUND: Laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) is a surgical method used to treat benign and low-grade malignant pancreatic head tumors. This study aimed to determine the protective effect of common bile duct in LDPPHR using indocyanine green (ICG) fluorescence imaging. METHODS: A retrospective analysis of 30 patients treated with LDPPHR at the Second Affiliated Hospital of Nanchang University between January 2015 and November 2022 was performed. Patients were divided into two groups based on ICG use: ICG and non-ICG. RESULTS: Thirty patients received LDPPHR, 11 males and 19 females, and the age was 50.50 (M (IQR)) years (range: 19-76 years). LDPPHR was successfully performed in 27 (90 %) patients, LPD was performed in 1 (3 %) patient, and laparotomy conversion was performed in 2 (7 %) patients. One patient (3 %) died 21 days after surgery. The incidence of intraoperative bile duct injury in the ICG group was lower than that in the non-ICG group (10 % vs 60 %, P = 0.009), and the operation time in the ICG group was shorter than that in the non-ICG group (311.9 ± 14.97 vs 338.05 ± 18.75 min, P < 0.05). Postoperative pancreatic fistula occurred in 16 patients (53 %), including 10 with biochemical leakage (62.5 %), four with grade B (25 %), and two with grade C (12.5 %). Postoperative bile leakage occurred in four patients (13 %). CONCLUSIONS: The ICG fluorescence imaging technology in LDPPHR helps protect the integrity of the common bile duct and reduce the occurrence of intraoperative bile duct injury, postoperative bile leakage, and bile duct stenosis.

Deciphering the molecular mediators of triclosan-induced lipid accumulation: Intervention via short-chain fatty acids and miR-101a.

As a potential environmental obesogen, triclosan (TCS) carries inherent risks of inducing obesity and metabolic disorders. However, the underlying molecular mechanisms behind the lipid metabolism disorder induced by TCS have remained elusive. Through a fusion of transcriptomics and microRNA target prediction, we hypothesize that miR-101a as a responsive miRNA to TCS exposure in zebrafish, playing a central role in disturbing lipid homeostasis. As an evidence, TCS exposure triggers a reduction in miR-10a expression that accompanied by elevation of genes linked to regulation of lipid homeostasis. Through precision-controlled interventions involving miRNA expression modulation, we discovered that inhibition of miR-101a enhanced expression of its target genes implicated in lipid homeostasis, subsequently triggering excessive fat accumulation. Meanwhile, the overexpression of miR-101a acts as a protective mechanism, counteracting the lipid metabolism disorder induced by TCS in the larvae. Notably, the combination of short-chain fatty acids (SCFAs) emerged as a potential remedy to alleviate TCS-induced lipid accumulation partially by counteracting the decline in miR-101a expression induced by TCS. These revelations provide insight into a prospective molecular framework underlying TCS-triggered lipid metabolism disorders, thereby paving the way for pre-emptive strategies in combating the ramifications of TCS pollution.

Knowledge, attitude, and practice of patients living with inflammatory bowel disease: A cross-sectional study.

BACKGROUND: Patients with inflammatory bowel diseases (IBDs) generally have poor knowledge, attitude, and practice of their disease, while the data from China are lacking. AIM: To address this knowledge disparity among Chinese patients with IBD. METHODS: This web-based, cross-sectional study was conducted on a cohort of IBD patients who visited the Second Affiliated Hospital of Wenzhou Medical University between December 2022 and February 2023. Their socio-demographic information and the knowledge, attitude, and practice scores were collected and estimated using a self-designed questionnaire. Pearson's correlation analysis was used to determine the pairwise correlations among knowledge, attitude, and practice scores. A multivariate logistic regression analysis was further performed to determine the independent factors associated with their knowledge, attitude, and practice scores. RESULTS: A total of 353 patients (224 males) with IBD completed the questionnaires. The mean knowledge, attitude, and practice scores were 10.05 ± 3.46 (possible range: 0-14), 41.58 ± 5.23 (possible range: 0-56), 44.20 ± 7.39 (possible range: 0-56), respectively, indicating good knowledge, positive attitude, and proactive practice toward IBD. Pearson's correlation analysis showed that the knowledge score had significant positive correlations with the attitude score (r = 0.371, P < 0.001) and practice score (r = 0.100, P < 0.001). The attitude score had a significant positive correlation with the practice score (r = 0.452, P < 0.001). Moreover, multivariate logistic regression analysis showed that aged 30-40 years [odds ratio (OR) = 4.06, 95% confidence interval (CI): 1.04-15.82, P = 0.043], middle school education (OR = 3.98, 95%CI: 1.29-12.33, P = 0.017), high school/technical secondary school education (OR = 14.06, 95%CI: 3.92-50.38, P < 0.001), and junior college/bachelor's degree and above education (OR = 15.20, 95%CI: 4.15-55.650, P < 0.001) were independently associated with good knowledge. The higher knowledge score was independently associated with a positive attitude (OR = 1.23, 95%CI: 1.11-1.36, P < 0.001). The higher attitude score was independently associated with proactive practice (OR = 1.20, 95%CI: 1.11-1.30, P < 0.001). CONCLUSION: Chinese patients with IBD might have good knowledge, a positive attitude, and proactive practice toward their disease. However, a small number of specific items require education.

Effects of repetitive transcranial magnetic stimulation over the contralesional dorsal premotor cortex on upper limb function in severe ischaemic stroke: study protocol for a randomised controlled trial.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment widely recommended to promote hand motor recovery after ischaemic stroke. However, the therapeutic efficacy of rTMS over the motor cortex in stroke patients is currently restricted and heterogeneous. This study aimed to determine whether excitatory rTMS over the contralesional dorsal premotor cortex (cPMd) facilitates the functional recovery of the upper limbs during the postacute stage of severe ischaemic stroke. METHODS AND ANALYSIS: This study will be conducted as a single-blind, controlled, randomised study, in which 44 patients with poststroke hemiplegia with a course of disease ranging from 1 week to 3 months and Fugl-Meyer upper limb score ≤22 will be enrolled. The study participants will be randomly assigned to groups A (n=22) and B (n=22). The two groups are based on routine rehabilitation training and drug treatment; group A will be treated with low-frequency (1 Hz) rTMS over the contralesional primary motor cortex (cM1), and group B will be treated with high-frequency (10 Hz) rTMS over cPMd. For 2 weeks, rTMS will be administered once a day, 5 days a week. The primary outcome is the Fugl-Meyer assessment of the upper limb. The secondary outcomes include the Arm Subscore of the Motricity Index, Hong Kong edition of Functional Test for the Hemiplegic Upper Extremity, Modified Barthel Index and Modified Ashworth Scale score of the paralysed pectoralis major and biceps brachii. Furthermore, data of diffusion tensor imaging and functional MRI will be collected. These outcomes will be assessed before and after the completion of the intervention. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (2020 SR-266). The findings of this study will be spread through networks of scientists, professionals and the general public as well as peer-reviewed scientific papers and presentations at pertinent conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000038049.

Training large-scale optoelectronic neural networks with dual-neuron optical-artificial learning.

Optoelectronic neural networks (ONN) are a promising avenue in AI computing due to their potential for parallelization, power efficiency, and speed. Diffractive neural networks, which process information by propagating encoded light through trained optical elements, have garnered interest. However, training large-scale diffractive networks faces challenges due to the computational and memory costs of optical diffraction modeling. Here, we present DANTE, a dual-neuron optical-artificial learning architecture. Optical neurons model the optical diffraction, while artificial neurons approximate the intensive optical-diffraction computations with lightweight functions. DANTE also improves convergence by employing iterative global artificial-learning steps and local optical-learning steps. In simulation experiments, DANTE successfully trains large-scale ONNs with 150 million neurons on ImageNet, previously unattainable, and accelerates training speeds significantly on the CIFAR-10 benchmark compared to single-neuron learning. In physical experiments, we develop a two-layer ONN system based on DANTE, which can effectively extract features to improve the classification of natural images.