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Abstract Painful diabetic neuropathy (PDN) is one of the most common complications of diabetes. Recent studies suggested that gut microbiota dysbiosis contributes to the development of PDN, but underlying mechanisms remain elusive. In this study, we found decreased probiotics generating bacteria such as Lactobacillus and Bifidobacterium strains in the PDN rats. Supplementation with multiple probiotics for 12 weeks alleviated pain, reversed nerve fiber lesions, and restored neuronal hyperexcitability. Probiotics administration effectively attenuated intestinal barrier impairment, reduced serum lipopolysaccharide and proinflammatory cytokines, and mitigated disruptions in the blood-nerve barrier. Furthermore, probiotics treatment inhibited the activation of the TLR4/MyD88/NF-κB signaling pathway and reduced proinflammatory cytokines in the sciatic nerve of the PDN rats. Together, our findings suggest that gut microbiota dysbiosis participates in PDN pathogenesis, and probiotics offer therapeutic potential via modulating the microbiota-gut-nerve axis. Graphical abstract

Abstract Background This study aims to evaluate the predictive usefulness of a habitat radiomics model based on ultrasound images for anticipating lateral neck lymph node metastasis (LLNM) in differentiated thyroid cancer (DTC), and for pinpointing high-risk habitat regions and significant radiomics traits. Methods A group of 214 patients diagnosed with differentiated thyroid carcinoma (DTC) between August 2021 and August 2023 were included, consisting of 107 patients with confirmed postoperative lateral lymph node metastasis (LLNM) and 107 patients without metastasis or lateral cervical lymph node involvement. An additional cohort of 43 patients was recruited to serve as an independent external testing group for this study. Patients were randomly divided into training and internal testing group at an 8:2 ratio. Region of interest (ROI) was manually outlined, and habitat analysis subregions were defined using the K-means method. The ideal number of subregions (n = 5) was determined using the Calinski-Harabasz score, leading to the creation of a habitat radiomics model with 5 subregions and the identification of the high-risk habitat model. Area under the curve (AUC) values were calculated for all models to assess their validity, and predictive model nomograms were created by integrating clinical features. The internal and external testing dataset is employed to assess the predictive performance and stability of the model. Results In internal testing group, Habitat 3 was identified as the high-risk habitat model in the study, showing the best diagnostic efficacy among all models (AUC(CRM) vs. AUC(Habitat 3) vs. AUC(CRM + Habitat 3) = 0.84(95%CI:0.71–0.97) vs. 0.90(95%CI:0.80-1.00) vs. 0.79(95%CI:0.65–0.93)). Moreover, integrating the Habitat 3 model with clinical features and constructing nomograms enhanced the predictive capability of the combined model (AUC = 0.95(95%CI:0.88-1.00)). In this study, an independent external testing cohort was utilized to assess the model’s accuracy, yielding an AUC of 0.88 (95%CI: 0.78–0.98). Conclusion The integration of the High-Risk Habitats (Habitat 3) radiomics model with clinical characteristics demonstrated a high predictive accuracy in identifying LLNM. This model has the potential to offer valuable guidance to surgeons in deciding the necessity of LLNM dissection for DTC. Clinical trial number Not applicable.

Objective: Clinical studies, epidemiological investigations and animal experiments have demonstrated that iron overload lead to bone loss, especially postmenopausal osteoporosis. As a physiotherapy tool, electromagnetic fields already used in clinical treatment of osteoporosis and participates in bone remodeling by affecting the iron metabolism of organisms. As an electromagnetic field with constant magnetic flux density and direction, the mechanism of static magnetic field (SMF) regulating iron metabolism remains unclear. Therefore, the aim of this study was to investigate the effects of moderate static magnetic field (MMF) on iron metabolism and bone metabolism in postmenopausal osteoporosis and HAMP-deficient mouse models, and to elucidate the underlying mechanisms. Methods: Firstly, the effects of MMF on bone metabolism and iron metabolism in 22 postmenopausal osteoporosis participants were evaluated by comparing the changes of bone mineral density (BMD) and serum ferritin before and after treatment. Secondly, 10-week-old male C57BL/6 HAMP+/+ and HAMP−/− mice were randomly divided into four groups, namely GMF-HAMP+/+ group and MMF-HAMP+/+ group, GMF-HAMP−/− group and MMF-HAMP−/− group (n = 8/group). The MMF-treated mice were exposed daily to MMF, while the remaining group was exposed to geomagnetic field (GMF) for 8 weeks. BMD was scanned and bone tissues were collected for mechanical, structural and histological analysis. In addition, analysis of serum and tissue iron content evaluated the regulation of systemic iron metabolism by MMF. Finally, the effects of MMF on the differentiation of primary macrophages and primary osteoblasts were evaluated in vitro. Results: In clinical trial, MMF decreased serum ferritin levels in postmenopausal osteoporosis patients, which was negatively correlated with changes in lumbar BMD. In vivo, the results showed that HAMP-deficient mice were accompanied by iron overload, along with reduced lumbar vertebra bone mass and bone quality. MMF improved the bone mass, microstructure and biomechanical properties of lumbar vertebrae in HAMP−/− mice. In vitro, MMF reduced the number and differentiation of osteoclasts in HAMP−/− mice, and promoted primary osteoblast differentiation by activating Wnt/β-catenin signaling pathway. Further, MMF also reduced the iron ion conversion and enhanced the antioxidant system of HAMP−/− mice. These data suggested that MMF could regulate iron metabolism and salvage bone loss caused by iron accumulation. Conclusions: The clinical trial and laboratory results suggested that MMF intervention has a protective effect on bone loss caused by iron metabolism disorders. Translational potential of this article: Translational potential of this article: This study demonstrated the feasibility and potential effectiveness of MMF in the treatment of postmenopausal osteoporosis patients, demonstrating for the first time that MMF can reduce bone loss in mice with inherited iron metabolism abnormalities. It was suggested that MMF plays an important role in iron metabolism disorders or as an alternative therapy to ameliorate osteoporosis caused by iron accumulation.

Background: Shuangshen granules (SSGs) are extensively utilized for the treatment of lung cancer in China and have been reported to possess tumor-protective and anti-metastatic effects. Therefore, it is crucial to understand the precise mechanism. Building upon the findings of our previous study, the objective of the present study was to explore the impact of SSGs on the sphingosine-1-phosphate receptor-1 (S1PR1)/signal transducer and activator of transcription 3 (STAT3) axis, as well as the recruitment of myeloid-derived suppressor cells (MDSCs) during the formation of the premetastatic niches (PMNs). Methods: In a mouse xenograft model utilizing Lewis lung carcinoma (LLC) cells that express green fluorescent protein (GFP), the initiation of lung metastasis was monitored every three days until day 35 following transplantation. Lung metastasis, MDSC recruitment, the expression of PMN and S1PR1/STAT3 axis biomarkers, as well as the blood levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-β (TGF-β) were assessed in the SSG treatment and control groups. Results: The LLC cells did not reach the lung until 14–17 days following subcutaneous implantation, which was concurrent with the formation of lung PMNs. SSG significantly postponed the initiation of lung metastasis and reduced the recruitment of MDSCs to the lung PMNs. SSG also suppressed the S1PR1/STAT3 axis in tumor tissues, bone marrow, and lung PMNs. Additionally, SSG suppressed the blood levels of GM-CSF and TGF-β, as well as the PMN markers, matrix metalloproteinase-9 and versican. Conclusion: Our findings suggested that SSG suppressed the development of MDSC-mediated PMNs by inhibiting the S1PR1/STAT3 axis, consequently postponing the initiation of lung metastasis.

Federated Learning (FL) is a novel distributed machine learning methodology that addresses large-scale parallel computing challenges while safeguarding data security. However, the traditional FL model in communication scenarios, whether for uplink or downlink communications, may give rise to several network problems, such as bandwidth occupation, additional network latency, and bandwidth fragmentation. In this paper, we propose an adaptive chained training approach (FedACT) for FL in computing power networks. First, a Computation-driven Clustering Strategy (CCS) is designed. The server clusters clients by task processing delays to minimize waiting delays at the central server. Second, we propose a Genetic-Algorithm-based Sorting (GAS) method to optimize the order of clients participating in training. Finally, based on the table lookup and forwarding rules of the Segment Routing over IPv6 (SRv6) protocol, the sorting results of GAS are written into the SRv6 packet header, to control the order in which clients participate in model training. We conduct extensive experiments on two datasets of CIFAR-10 and MNIST, and the results demonstrate that the proposed algorithm offers improved accuracy, diminished communication costs, and reduced network delays.

Abstract This study investigated the prevalence and severity of lower urinary tract symptoms (LUTS) in children with spastic cerebral palsy (SCP) and evaluated the effect of selective dorsal rhizotomy (SDR) in alleviating these symptoms. The study also explored the correlation between postoperative LUTS improvement and intraoperative electrophysiological findings. Prospective data were collected from a consecutive cohort of 247 children with SCP who underwent SDR and were retrospectively analyzed. Pre- and post-operative assessments included muscle tone, motor function, LUTS and intraoperative electrophysiology data were analyzed. Preoperatively, 94 patients (38.1%) had LUTS, and the severity of LUTS negatively correlated with motor function (R=-0.32, P 20µV. SDR effectively reduces spasticity, improves motor function, and alleviates LUTS in most children with SCP. Intraoperative neurophysiology may predict improvements, warranting further research.

Background: Following recent research advancements, an increasing level of evidence had been published to indicate that celastrol exerted a therapeutic effect on a range of nervous system diseases. This study therefore aimed to investigate the potential involvement of celastrol on ferroptosis and the blood-brain barrier disruption in intracerebral haemorrhage. Methods: We established a rat intracerebral haemorrhage and adrenal pheochromocytoma cell (PC12) OxyHb models using an ACSL4 overexpression vector. Ferroptosis-related indices were assessed using corresponding assay kits, and immunofluorescence and flow cytometry were used to measure reactive oxygen species (ROS) levels. Additionally, quantitative PCR (qPCR) and western blot analyses were conducted to evaluate the expression of key proteins and elucidate the role of celastrol in intracerebral haemorrhage (ICH). Results: Celastrol significantly improved neurological function scores, blood-brain barrier integrity, and brain water content in rats with ICH. Moreover, subsequent analysis of ferroptosis-related markers, such as Fe2+, ROS, MDA, and SOD, suggested that celastrol exerted a protective effect against the oxidative damage induced by ferroptosis in ICH rats and cells. Furthermore, Western blotting indicated that celastrol attenuated ferroptosis by modulating the expression levels of key proteins, including acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and anti-transferrin receptor 1 (TFR1) both in vitro and in vivo. ACSL4 overexpression attenuated the neuroprotective effects of celastrol on ICH in vitro. Molecular docking analysis revealed that celastrol interacted with ACSL4 via the GLU107, GLN109, ASN111, and LYS357 binding sites. Conclusions: Celastrol exerted antioxidant properties and aids in neurological recovery after stroke by suppressing ACSL4 expression during ferroptosis. As such, this drug represented a promising pharmaceutical candidate for the treatment of ICH.

Abstract Background Cigar tobacco leaves contain abundant bacteria and fungi that are vital for their quality. In this study, the microbial communities were analyzed in the artificial mildewed cigar tobacco leaves of different mildew stages (healthy control, early stage, middle stage and late stage). Results For cigar wrapper tobacco leaves, there was an increased bacterial genera abundance of Terribacillus, Bacillus and Micrococcus, while there was an increased fungal genera abundance of Aspergillus, Penicillium and Mucor. For cigar filler tobacco leaves, there was an increased bacterial genera abundance of Staphylococcus, while there was an increased fungal genera abundance of Aspergillus and Trichomonascus. Microbial communities (bacterial and fungal) showed significantly different compositions in both cigar wrapper and filler tobacco leaves from different mildew stages. The top important microbial communities (bacterial and fungal) in cigar wrapper and filler tobacco were Sphingomonas, Aerococcus, Wallemia and Trichomonascus, respectively. Conclusion This study provided evidence for the great changes in microbial communities during the mildew process of cigar wrapper and filler tobacco. The effects of the dominant bacterial genera and fungal genera on tobacco mildew should be explored in depth, whose findings may be applied to develop strategies for controlling tobacco mildew.

Abstract CRISPR diagnostics are effective but suffer from low signal transduction efficiency, limited sensitivity, and poor stability due to their reliance on the trans-cleavage of single-stranded nucleic acid fluorescent reporters. Here, we present CrisprAIE, which integrates CRISPR/Cas reactions with “one to more” aggregation-induced emission luminogen (AIEgen) lighting-up fluorescence generated by the trans-cleavage of Cas proteins to AIEgen-incorporated double-stranded DNA labeled with single-stranded nucleic acid linkers and Black Hole Quencher groups at both ends (Q-dsDNA/AIEgens-Q). CrisprAIE demonstrates superior performance in the clinical nucleic acid detection of norovirus and SARS-CoV-2 regardless of amplification. Moreover, the diagnostic potential of CrisprAIE is further enhanced by integrating it with spherical nucleic acid-modified AIEgens (SNA/AIEgens) and a portable cellphone-based readout device. The improved CrisprAIE system, utilizing Q-dsDNA/AIEgen-Q and SNA/AIEgen reporters, exhibits approximately 80- and 270-fold improvements in sensitivity, respectively, compared to conventional CRISPR-based diagnostics. We believe CrisprAIE can be readily extended as a universal signal generation strategy to significantly enhance the detection efficiency of almost all existing CRISPR-based diagnostics.

Abstract Ferroptosis is a cell death modality in which iron-dependent lipid peroxides accumulate on cell membranes. Cysteine, a limiting substrate for the glutathione system that neutralizes lipid peroxidation and prevents ferroptosis, can be converted by cystine reduction or synthesized from methionine. However, accumulating evidence shows methionine-based cysteine synthesis fails to effectively rescue intracellular cysteine levels upon cystine deprivation and is unable to inhibit ferroptosis. Here, we report that methionine-based cysteine synthesis is tissue-specific. Unexpectedly, we find that rather than inhibiting ferroptosis, methionine in fact plays an essential role during cystine deprivation-induced ferroptosis. Methionine-derived S-adenosylmethionine (SAM) contributes to methylation-dependent ubiquinone synthesis, which leads to lipid peroxides accumulation and subsequent ferroptosis. Moreover, SAM supplementation synergizes with Imidazole Ketone Erastin in a tumor growth suppression mouse model. Inhibiting the enzyme that converts methionine to SAM protects heart tissue from Doxorubicin-induced and ferroptosis-driven cardiomyopathy. This study broadens our understanding about the intersection of amino acid metabolism and ferroptosis regulation, providing insight into the underlying mechanisms and suggesting the methionine-SAM axis is a promising therapeutic strategy to treat ferroptosis-related diseases.

Abstract This study aimed to assess the effectiveness and safety of 5-Fluorouracil (5-Fu) combined with conventional transarterial chemoembolization (cTACE) compared to 5-Fu combined with drug-eluting bead transarterial chemoembolization (DEB-TACE) using CalliSpheres for the treatment of unresectable hepatocellular carcinoma (HCC) using propensity score weighting methods. This retrospective analysis included 131 patients with HCC treated with 5-Fu combined with cTACE (5-Fu-cTACE group, n = 65) or DEB-TACE (5-Fu-DEB-TACE group, n = 66) at the Affiliated Hospital of North Sichuan Medical College from January 2019 to December 2022. Based on the baseline data and laboratory indicators, propensity score weighting was used to reduce confounding bias. Modified response evaluation criteria in solid tumors (mRECIST) were used to evaluate clinical efficacy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the disease control rate (DCR), objective response rate (ORR) and adverse events (AEs). PFS was assessed using Kaplan‒Meier analysis and Cox proportional hazards models. The ORRs at 1 month (M1) after treatment in the 5-Fu-DEB-TACE group and 5-Fu-cTACE group were 90.9% and 76.9%, respectively (P = 0.029), while at this time, the DCRs were 93.9% in the 5-Fu-DEB-TACE group and 90.8% in the 5-Fu-cTACE group (P = 0.494). At 3 months (M3) after treatment, the 5-Fu-DEB-TACE group had a higher ORR (84.8% vs. 56.9%, P

To improve the light environment of asymmetric large-span externally insulated plastic greenhouses, a solar radiation model that considers the projection path equations of the insulation quilts and validated the model was established. The model was employed to investigate the impact of different heights, spans, and north lighting projection lengths on the greenhouses' light environment. The results revealed that ground radiation interception, a key component of winter lighting, was most influenced by height, followed by span, and least influenced by the projection length of the north lighting roof. Additionally, ground radiation spatial uniformity was most affected by height, followed by the projection length of the north lighting roof, and least influenced by span. The optimization objectives for solar radiation were set to maximize solar radiation interception and minimize the coefficient of variation. The optimal structural parameters for the asymmetric large-span externally insulated plastic greenhouse were determined using the NSGA-II method and the entropy weight-TOPSIS method: the height of 6.97 m, and the projection length of north lighting roof is 7.44 m for a greenhouse with a span of 20.00 m. Compared to the initial greenhouse, the optimized design enhances both radiation interception performance and ensures uniform light distribution. These results offer valuable theoretical guidance for greenhouse construction.

ObjectivesThis study aimed to evaluate the effectiveness of combining hepatic arterial infusion chemotherapy (HAIC) with lenvatinib and programmed cell death protein 1 (PD-1) inhibitors in the treatment of advanced, unresectable hepatocellular carcinoma (HCC).MethodsA comprehensive search across multiple databases was conducted to identify relevant studies published up to May 2024. This search focused on clinical trials investigating the combination of HAIC with lenvatinib and PD-1 inhibitors for the treatment of advanced HCC. Data from these trials were analyzed using either fixed-effects or random-effects models, with results reported as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs). To evaluate the robustness of the findings, trial sequential analysis was employed.ResultsA total of 8 cohort studies encompassing 1073 patients with unresectable HCC were included. Compared with other treatment regimens, the combined use of HAIC, lenvatinib, and PD-1 inhibitors significantly improved overall survival (OS) (HR=0.53 [95% CI 0.45, 0.63], P

Abstract As a vegetable and spice crop, the quality of pepper (Capsicum annuum L.) is considerably affected by flavor. However, research on flavor of different C. annuum L. varieties, such as the fruits of “Gansu Xianjiao” (GX) and “Gansu Banjiao” (GB), is limited. In this study, comprehensive two‐dimensional gas chromatography with time‐of‐flight mass spectrometry and multivariate statistical analysis were used to elucidate the flavor differences between GX and GB. A total of 2458 volatile organic compounds (VOCs) were identified, with GX and GB possessing 1914 and 1802 VOCs, respectively. Multivariate statistical analysis revealed 215 differential VOCs in GX versus GB. The relative contents of pyrazine, 2‐ethenyl‐6‐methyl and 1‐cyclohexene‐1‐carboxylic acid, 2,6,6‐trimethyl‐, ethyl ester were most significantly increased, whereas those of 4‐methylpentyl 4‐methylpentanoate methional and 2‐furanmethanol,5‐methyl‐ were most significantly decreased. Further, these differential VOCs were correlated with sensory attributes, such as the sweetness, fruitiness, and green aroma. This study will provide deeper insights into improving the flavor quality of C. annuum L.

Introduction: An expanding body of research has explored the crucial role of gut microbiota in cerebral small vessel disease (CSVD). The objective of this study is to investigate alterations in the gut microbiota structure among CSVD patients, to explore the correlation between differential taxonomic levels and the neurovascular coupling index as well as cognitive function and to elucidate the imaging and biomarkers of mild cognitive impairment (MCI) in CSVD. Methods: We enrolled 104 patients with CSVD and 40 healthy controls (HC). Based on cognitive test scores, CSVD patients were categorized into a cognitively normal group (CSVD-NCI, n=61) and a mild cognitive impairment group (CSVD-MCI, n=43). Performing magnetic resonance imaging (MRI) scans, gut microbiota analysis, as well as clinical and neuropsychological assessments for all participants. Based on arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) imaging data, cerebral blood flow (CBF) and neural activity indices are computed. The coupling indices of CBF/mReHo, CBF/mfALFF, CBF/mALFF, and CBF/mDC are calculated to assess the whole-brain neurovascular coupling changes in patients with CSVD. Results: Species annotation revealed differences in the composition at the phylum and genus levels among the HC, CSVD-NCI, and CSVD-MCI groups. Additionally, differential analysis using the Kruskal-Wallis test demonstrated specific dominant microbial communities in all three groups. The relative abundance of certain dominant microbial communities in CSVD patients exhibited correlations with neurovascular coupling and cognitive function. The combined assessment of Bacteroides genus and CBF/mDC proved effective in distinguishing between CSVD-NCI and CSVD-MCI, providing a novel non-invasive approach for the diagnosis of MCI in CSVD.

Business Development (BD) activities have become prevalent in practice, and prior research has demonstrated their potential to enhance and complement the core competencies of enterprises. However, the limited and fragmented existing literature on Business Development highlights the need for a comprehensive integration effort to reassess the theoretical foundation and overall concept. This article comprehensively reviews 125 papers on Business Development, investigates enterprises’ responses to business environment changes (which encompass environmental adaptation and resource leverage, environmental management and resource allocation, environmental creation and resource alignment, and environmental exploration and resource development), and clarifies the evolutionary trajectory of the Business Development literature research stream. Furthermore, we advance a comprehensive conceptual framework and theoretical model to identify a network of constructs and their connections with crucial dimensions of Business Development. The findings of this study significantly contribute to understanding Business Development and provide valuable insights for future research and practice.

Traumatic brain injury (TBI) can lead to neurodegenerative diseases such as Alzheimer's disease (AD) through mechanisms that remain incompletely characterized. Similar to AD, TBI models present with cellular metabolic alterations and modulated cleavage of amyloid precursor protein (APP). Specifically, AD and TBI tissues display increases in amyloid-β as well as its precursor, the APP C-terminal fragment of 99 a.a. (C99). Our recent data in cell models of AD indicate that C99, due to its affinity for cholesterol, induces the formation of transient lipid raft domains in the ER known as mitochondria-associated endoplasmic reticulum (ER) membranes ("MAM" domains). The formation of these domains recruits and activates specific lipid metabolic enzymes that regulate cellular cholesterol trafficking and sphingolipid turnover. Increased C99 levels in AD cell models promote MAM formation and significantly modulate cellular lipid homeostasis. Here, these phenotypes were recapitulated in the controlled cortical impact (CCI) model of TBI in adult mice. Specifically, the injured cortex and hippocampus displayed significant increases in C99 and MAM activity, as measured by phospholipid synthesis, sphingomyelinase activity and cholesterol turnover. In addition, our cell type-specific lipidomics analyses revealed significant changes in microglial lipid composition that are consistent with the observed alterations in MAM-resident enzymes. Altogether, we propose that alterations in the regulation of MAM and relevant lipid metabolic pathways could contribute to the epidemiological connection between TBI and AD.

Chinese tongue sole (Cynoglossus semilaevis) is a traditional, nutrient rich and economically valuable fish that is important for mariculture in China. It has small visceral masses, few spines, with tender and tasty flesh. Studies on the sexing mechanism of fish were carried out since the revelation of sexual reversal and hermaphroditism in the eel. Sex is the most common biological phenomenon and there are significant differences in morphology, reproductive strategies, and behavior between females and males of many organisms. Sole is a typical representative of the heterogeneous growth of males and females: adult females are approximately 2–4 times larger than males. This has constrained the sustainable development of the sole culture industry. Why do females grow faster than males? Do sex differentiation-related genes play a role in sex determination and size heteromorphism in sole? Answering these questions has important implications and applications in the genetic improvement and development of sole farming.Rimoc1 encodes a protein in the inner mitochondrial membrane that is involved in regulating the activity of complex Ⅰ of the mitochondrial respiratory chain that affects mitochondrial respiratory function. Rimoc1 interacts with the NDUFAF1 subunit of complex Ⅰ in the inner mitochondrial membrane and enhances its affinity for NADH. This increases the catalytic activity of complex Ⅰ and increases the rate of electron transfer in the mitochondrial respiratory chain. In addition, RIMOC1 interacts with proteins in other mitochondrial respiratory chain complexes (such as complex Ⅲ and complex Ⅳ) and may play a role in regulating the overall stability and function of the mitochondrial respiratory chain.This study aimed to investigate the expression differences of the rimoc1 gene in male and female Chinese tongue sole and determine its potential relationship with sex and growth. Rimoc1 expression was highest in the ovaries and muscles of females; it was not expressed in male tissues. Interestingly, its expression was relatively stable in the ovaries, but increased at 1.5- and 3-years post-hatching. Knocking out rimoc1 through siRNA interference in cell lines significantly reduced the expression levels of growth-related gene igf1, and sex differentiation-related genes sox9b and foxl2, while sox9a expression increased. Promoter activity analysis further demonstrated that the rimoc1 promoter strongly responded to transcription factors C/EBPdelta, Sox2, and c-Jun. This suggested their potential role in regulating rimoc1. Sex determination in semislipped sole occurs at approximately 50 days, while gonadal differentiation begins at 60 days. However, differentiation at the cellular level is relatively delayed, with ovarian cell differentiation usually occurring at 90–120 days with the emergence of an ovarian cavity followed by continued oocyte differentiation and sexual maturity at approximately 2 years of age. Thus, high rimoc1 expression at 90 days is consistent with the differentiation of naturally growing ovarian cells in semi-smooth tongue sole.Analysis of promoter activity showed that rimoc1 was transcriptionally active at 981 bp upstream and had strong initiation activity. The activity was enhanced following cotransfection with three transcription factors (C/EBPalpha, Sox2, and C-Jun), although only the C/EBPalpha group was significantly different. This suggested that these three transcription factors exert an enhancing effect on rimoc1 transcription. It is known that C/EBPalpha plays a major role in keratinocyte and adipocyte differentiation. However, its regulation of rimoc1 in hemipterous sole requires further investigation.There are few reports on the function of rimoc1 in sexual differentiation. Therefore, we performed the first functional investigation of rimoc1 by siRNA-mediated RNA interference in an ovarian cell line. Quantitative polymerase chain reaction showed that the expression levels of igf1, sox9a, sox9b, and foxl2 changed at different degrees after rimoc1 gene interference compared to the control group; sox9a expression was up-regulated, while the expression of igf1, sox9b, and foxl2 was down-regulated. Fish igf1 is closely related to reproductive function and gonadal development. Tilapia igf1 expression was detected from the early stages of oogenesis till oocyte maturation. At the same time, Igf1 is involved in regulating growth hormones and growth. Sexual growth dimorphism begins to appear in one-year old half-sauropod sole. The quantification of different developmental stages shows that rimoc1 expression starts to increase at 180 days until its peak expression at 1.5 years of age. It is worthwhile investigating whether rimoc1 has a potential regulatory function in growth.Sox9 is a key transcription factor that plays an important role in regulating the proliferation and differentiation of various cell types. It has a critical role in embryonic development, with expression occurring throughout this period. Its level is maintained in adult tissues and plays an important role in the repair of postnatal damage in endodermal and ectodermal organs. It has a role in sex differentiation, with sox9a and cyp19a together forming a regulatory pathway for sexual differentiation. We hypothesize that rimoc1 is involved in ovarian development and oogenesis by regulating the steroid hormone pathway. Sox9b is highly expressed in the gonads of early semi-smooth sole, and rimoc1 knockdown results in its reduced expression. This suggests that Rimoc1 and Sox9b act together to regulate Foxl2 and play a role in sex determination and differentiation, ovarian development and maintenance, embryonic development, and immune regulation in the animal. The foxl2 gene positively regulates ovarian differentiation in mice, and its sustained expression inhibits abnormal differentiation of ovarian cells to testicular cells during growth and development, thereby maintaining the female sex. Meanwhile foxl2 deletion can lead to poor ovarian development, and even female sterility. Rimoc1 knockdown results in its reduced expression, suggesting that rimoc1 may be closely associated with ovarian development in hemipelagic sole. Therefore, a deeper understanding of the function and regulatory mechanisms of rimoc1 may be the key to resolving sexual growth dimorphism.Our results suggest that rimoc1 plays a crucial role in sex differentiation and growth of Chinese tongue sole. These findings provide a foundation for further investigations into the sexual growth dimorphism of this species.

Abstract One of the focal points in the field of intelligent transportation is the intelligent control of traffic signals (TS), aimed at enhancing the efficiency of urban road networks through specific algorithms. Deep Reinforcement Learning (DRL) algorithms have become mainstream, yet they suffer from inefficient training sample selection, leading to slow convergence. Additionally, enhancing model robustness is crucial for adapting to diverse traffic conditions. Hence, this paper proposes an enhanced method for traffic signal control (TSC) based on DRL. This approach utilizes dueling network and double q-learning to alleviate the overestimation issue of DRL. Additionally, it introduces a priority sampling mechanism to enhance the utilization efficiency of samples in memory. Moreover, noise parameters are integrated into the neural network model during training to bolster its robustness. By representing high-dimensional real-time traffic information as matrices, and employing a phase-cycled action space to guide the decision-making of intelligent agents. Additionally, utilizing a reward function that closely mirrors real-world scenarios to guide model training. Experimental results demonstrate faster convergence and optimal performance in metrics such as queue length and waiting time. Testing experiments further validate the method's robustness across different traffic flow scenarios.

Abstract The dry reforming of methane provides an attractive route to convert greenhouse gases (CH4 and CO2) into valuable syngas, so as to resolve the carbon cycle and environmental issues. However, the development of high-performance catalysts remains a huge challenge. Herein, we report a 0.6% Ir/CeO2−x catalyst with a metal-support interface structure which exhibits high CH4 (~72%) and CO2 (~82%) conversion and a CH4 reaction rate of ~973 μmolCH4 gcat −1 s−1 which is stable over 100 h at 700 °C. The performance of the catalyst is close to the state-of-the-art in this area of research. A combination of in situ spectroscopic characterization and theoretical calculations highlight the importance of the interfacial structure as an intrinsic active center to facilitate the CH4 dissociation (the rate-determining step) and the CH2* oxidation to CH2O* without coke formation, which accounts for the long-term stability. The catalyst in this work has a potential application prospect in the field of high-value utilization of carbon resources.

Abstract Purpose This study evaluates biochar from crop residues as a solution to soil degradation in continuous monoculture within greenhouse agriculture, focusing on its impact on soil microbial communities and cucumber plant growth. Methods We analyzed biochar derived from tomato straw (TSB), sweet pepper straw (SPSB), and eggplant straw (ESB), assessing their nutrient content, cation exchange capacity, and adsorption rates. This study examined the effects of three concentrations (2.5%, 5%, and 7.5% w/w) of the more promising SPSB on soil properties and cucumber growth. Results SPSB showed significantly higher levels of nitrogen, phosphorus, and potassium, along with superior adsorption capacity compared to TSB and ESB. The 5% w/w SPSB concentration notably improved cucumber growth, increasing plant height by 13.01%, stem thickness by 20.79%, leaf area by 50.26%, and dry weight by 58.56% relative to the control. High-throughput sequencing revealed this concentration significantly altered soil microbial community structure, enhancing bacterial and fungal diversity. It increased beneficial bacterial groups (Firmicutes, Actinobacteria, Bacillus) and modified fungal communities, with a decrease in Ascomycota and Aspergillus and shifts in Penicillium abundance. Functional genomic analysis indicated enrichment in bacterial metabolic pathways and fungal replication and expression genes. Conclusion SPSB, especially at a 5% w/w concentration, emerges as an effective soil amendment in greenhouses affected by continuous monoculture. This approach represents a sustainable method to enhance soil health and crop productivity.