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Abstract To develop and validate a machine learning (ML) model which combined computed tomography (CT) semantic and radiomics features to preoperatively predict Ki-67 expression in gastrointestinal stromal tumors (GISTs) patients. We retrospectively collected the clinical, imaging and pathological data of 149 GISTs patients. We randomly assigned the patients in a ratio of 7:3 to a training set (104 cases) and a validation (45 cases) set. We divided the patients into low and high Ki-67 expression group according to postoperative pathology. CT semantic features were analyzed from preoperative enhancement CT images and radiomics features were extracted from venous phase-enhanced images. We used intraclass correlation coefficient, maximal relevance and minimal redundancy and least absolute shrinkage and selection operator method to screen radiomics features and build radiomics label. 6 ML models were used for model construction. Receiver operating characteristic curves were used to evaluate the predictive efficiency of ML models. SHAP analysis was used to explain the contribution of different variables and their risk threshold. AUC of radscores in predicting Ki-67 expression of GIST patients were 0.749 and 0.729 in training and validation set. Among the 6 ML models, SVM exhibited best prediction accuracy. AUC of SVM model in predicting Ki-67 expression of GIST patients were 0.840, 0.767 and 0.832 in training, validation and test set. SHAP analysis showed that radscores and tumor diameter had highly positive contribution to the model. Therefore, the interpretable SVM model can predict Ki-67 expression of GISTs patients individually before surgery, which can provide reliable imaging biomarkers for clinical treatment decisions.

Abstract Synthetic aperture radar (SAR) is crucial for military reconnaissance and remote sensing, but image quality can be affected by various factors, impacting target detection performance. Thus, pre-evaluation of SAR image quality is essential to filter out poor-quality images, optimize resource allocation, and enhance detection accuracy and efficiency. This paper proposes a comprehensive SAR image quality evaluation method combining objective and subjective approaches. Specifically, the processes encompassing the generation of a series of disturbed SAR images on the SAR ship detection dataset (SSDD), the calculation of various objective quality indicators for those images, and the assignment of a subjective quality label to each image through subjective evaluation. Based on the dataset constructed by the above evaluation methods, the IHHO-XGBoost model was developed. This model uses an improved harris hawk optimization (IHHO) algorithm to optimize extreme gradient boosting (XGBoost) hyperparameters. The IHHO algorithm effectively alleviates the problem of getting trapped in local optima by improving the escape energy calculation strategy and integrating the average difference evolution mechanism while maintaining the diversity of the population, showing significant advantages over the traditional HHO algorithm. Comparative experiments demonstrate the model’s superiority in SAR image quality evaluation. This study validates the scientificity and practicability of the proposed method, offering new tools for SAR image quality research.

Abstract To evaluate the levels of YKL40, IL-6(interleukin-6), IL-8(interleukin-8), IL-10(interleukin-10), TNF-α (tumor necrosis factor-α) in OSAS (obstructive sleep apnea syndrome)children and explore the mechanism of YKL40 promoting inflammatory factors overexpression in tonsils. qPCR and ELISA were used to identify the expression of YKL40, IL-6, IL-8, IL-10, and TNF-α in the tonsils of OSAS children. Primary tonsil lymphocytes (PTLCs) were cultured and recombinant human YKL40(rhYKL40)was used to stimulate PTLCs in different concentrations and at different time points. The activation of NF-κB in PTLCs was screened by western blotting. Relative mRNA of YKL40, IL-6, IL-8, TNF-α was over expressed in OSAS-derived tonsil tissue and the levels of YKL40, IL-6, IL-8, and TNF-α was increased in OSAS-derived protein supernatant of tonsil tissue.The relative mRNA expression of IL-6, IL-8 and TNF-α increased under the treatment of YKL40 (100 ng/mmol for 24 h). The phosphorylation of p65 in NF-κB pathway was stimulated in the process. The levels of YKL40, IL-6, IL-8, and TNF-α increases in OSAS children, and YKL40 promotes the overexpression of IL-6, IL-8 and TNF-α in PTLCs via NF-κB pathway. The result implements that inflammation may play an important role in the pathogenesis of OSAS in children.

Abstract Background Shen-Bai-Jie-Du decoction (SBJDD), a traditional Chinese herb formula developed based on evidence-based medicine, is efficacy to reduce the recurrence and carcinogenesis of colorectal adenoma. However, the mechanism of SBJDD to treat colorectal adenoma remains unclear. The present study aims to investigate the efficacy and mechanism of SBJDD on colorectal adenoma carcinogenesis from the aspects of regulating gut microbiota and short-chain fatty acids (SCFAs). Methods Twenty-one patients diagnosed with colorectal adenoma were recruited in the study and required to take SBJDD for four consecutive weeks. Analysis of gut microbiota was conducted using 16S rRNA gene amplicon sequencing, while levels of SCFAs in fecal and serum samples were determined through HPLC–MS/MS. Additionally, twenty-four Apcmin/+ mice were randomly assigned to normal diet (ND), high-fat diet (HFD), and SBJDD groups. The pharmacological effects and mechanism of SBJDD on colorectal adenoma carcinogenesis were assessed using RT-qPCR, HE staining, IHC staining, Western blot, IF staining, and Flow cytometry assays. Results Our clinical study has shown that SBJDD can regulate the gut microbiota composition and enhance SCFAs production in patients with colorectal adenoma. SBJDD alleviated colorectal adenoma formation and carcinogenesis, as well as protected the integrity of the intestinal barrier in the Apcmin/+ mice model compared to the HFD group. Additionally, SBJDD was found to regulate gut microbiota capable of producing SCFAs. G protein-coupled receptors GPR43, GPR41, and GPR109a were effectively activated in the SBJDD group, while HDAC1 and HDAC3 were inhibited. Furthermore, decreased expression levels of interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), along with elevated expression level of interleukin 10 (IL-10), were observed in the colorectal tissue of the SBJDD group. Finally, SBJDD exhibited the ability to reduce the proportion of M1-type macrophages while increasing the proportion of M2-type macrophages. Conclusions Our study objectively demonstrated the pharmacological effects of SBJDD in inhibiting the progression of colorectal adenoma and investigated its mechanisms in terms of regulating gut microbiota, increasing SCFAs, and reducing colorectal inflammation.

Automatic modulation recognition (AMR) stands as a pivotal operation within industrial cognitive radio systems. State-of-the-art real-valued convolutional neural networks (CNNs) have innovated modulation recognition but view complex signal components as separate real inputs, impairing signal phase integrity and model interpretability. This paper presents an innovative AMR method known as the CVCNN-LSTM. Our study aims to leverage CNNs in conjunction with a long short-term memory network (LSTM) to harness the strengths of both networks while mitigating their weaknesses. This approach enhances the learning of original I/Q signal features, thus improving recognition performance. The proposed network is composed of multiple LFLBs and an LSTM layer. Each LFLBs is primarily composed of a convolutional layer and an average pooling layer, which play a key role in enabling local correlation learning and hierarchical correlation extraction. Recognizing that I/Q data inherently possesses a complex-valued structure, we advocate using end-to-end complex-valued CNN and complex-valued LSTM instead of dual-channel real-valued networks for modulation recognition. We conduct experiments to evaluate complex-valued networks and demonstrate that our method surpasses current state-of-the-art approaches in the AMR field.

Abstract Background The mandibular retromolar space (RMS) has not been extensively studied in relation to various sagittal skeletal classes and patterns of third-molar eruption. The objective of this study was to test the null hypothesis that there is no difference in the mandibular RMS among normodivergent subjects with different skeletal classes and patterns of mandibular third-molar eruption, using cone-beam computed tomography (CBCT). Method A total of 105 normodivergent patients (20–40 years) were included in this study. Participants were categorized into Class I, II and III groups based on ANB and further impacted and erupted groups based on the eruption patterns of the mandibular third molars. Measurements of the mandibular RMS were taken at four planes parallel to the occlusal plane, along the cusp line. Comparative analyses were conducted among the three sagittal groups and between the impacted and erupted groups. Results The Class II group exhibited a statistically smaller RMS (P

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) patients are at an elevated risk of developing severe coronavirus disease 2019 (COVID-19). The objective of this study was to assess antibody responses and safety profiles six months after the third dose of the inactivated acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in MASLD patients. Methods This study included MASLD patients and healthy volunteers without a history of SARS-CoV-2 infection. Blood samples were collected six months after receiving the third dose of the inactivated vaccine to measure the levels of neutralizing antibodies (NAbs) and anti-spike IgG antibodies against SARS-CoV-2. Results A total of 335 participants (214 MASLD patients and 121 healthy volunteers) were enrolled. The seroprevalence of NAb was 61.7% (132 of 214) in MASLD patients and 74.4% (90 of 121) in healthy volunteers, which was a significant difference (p = 0.018). Statistically significant differences in IgG seroprevalence were also observed between MASLD patients and healthy volunteers (p = 0.004). Multivariate analysis demonstrated that the severity of MASLD (OR, 2.97; 95% CI, 1.32–6.68; p = 0.009) and age (OR, 1.03; 95% CI, 1.01–1.06; p = 0.004) were independent risk factors for NAb negativity in MASLD patients. Moderate/severe MASLD patients had a lower NAb seroprevalence than mild MASLD patients (45.0% vs. 65.5%, p = 0.016). Conclusion Lower antibody responses were observed in MASLD patients six months after their third dose of the inactivated vaccine than in healthy volunteers, providing further assistance in monitoring patients who are more vulnerable to hypo-responsiveness to SARS-CoV-2 vaccines.

Abstract Extrusion-based three-dimensional (3D) printing of gelatin (Gel) is crucial for fabricating bone tissue engineering scaffolds via additive manufacturing. However, the thermal instability of Gel remains a persistent challenge, as it tends to collapse at mild temperatures. Current approaches often involve simply mixing Gel particles with various materials, resulting in biomaterial inks that lack uniformity and have inconsistent degradation characteristics. In this study, acetic acid was used to dissolve Gel and polycaprolactone (PCL) separately, producing homogeneous Gel/PCL dispersions with optimal pre-treatment performance. These dispersions were then combined and hybridized with nano-hydroxyapatite (n-HA) to create a composite printing ink. By evaluating the printability of the ink, the optimal conditions were identified: a n-HA concentration of 50% (w/w), a printing temperature of 10–15 ℃, a printing pressure of 2.5 bar, and a printing speed of 7 mm/s. The resulting biomaterial inks, with a composition of 25% Gel, 25% PCL, and 50% n-HA, demonstrated excellent printability and stability, along with significantly enhanced mechanical properties. As a result, 3D scaffolds with high printability and shape fidelity can be printed at room temperature, followed by deep freezing at -80 ℃ and cross-linking with vanillin. The Gel-based composite scaffolds demonstrated excellent biocompatibility, cell adhesion, cell viability and nano-hydroxyapatite absorption in vitro. Additionally, in vivo experiments revealed that the bioactive scaffold biodegraded during implantation and significantly promoted bone regeneration at the defect site. This provides a promising strategy for treating bone defects in clinical setting. In conclusion, the Gel/PCL/n-HA biomaterial inks presented here offer an innovative solution for extrusion bioprinting in the field of bone tissue engineering. Graphical Abstract

Introduction: Natural products (NPs) play a crucial role in the development of therapeutic drugs. However, it is still highly challenging to identify the targets of NPs. Besides, NPs usually exert their pharmacological activities via acting on multiple targets or pathways, which also poses great difficulties for the target identification of NPs. Objectives: Inspired by our continuous efforts in designing drug-like protein degraders, this study introduced a successful example for the target identification and drug discovery of natural products evodiamine by employing PROTAC technology. Methods: Taking advantages of proteolysis targeting chimera (PROTAC), herein an integrated strategy combining PROTAC derivatization, quantitative proteomic analysis and binding affinity validation was developed for target identification and drug discovery of antitumor NP evodiamine. Results: In this study, both highly potent PROTACs and negative controls were designed for quantitative proteomic analysis. Furthermore, REXO4 was confirmed as a direct target of 3-fluoro-10-hydroxylevodiamine, which induced cell death through ROS. In addition, the PROTAC 13c effectively degraded REXO4 both in vitro and in vivo, leading to potent antitumor activities and reduced toxic side effects. Conclusion: In summary, we developed an integrated strategy for the target identification and drug discovery of NPs, which was successfully applied to the PROTAC derivatization and target characterization of evodiamine. This proof-of-concept study highlighted the superiority of PROTAC technology in target identification of NPs and accelerated the process of NPs-based drug discovery, exhibiting broad application in NP-based drug development.

In this study, a dense WS2 coating was deposited via high-power impulse magnetron sputtering (HiPIMS) after solving the glow discharge problem, and it was compared with WS2 coating deposited via radio frequency (RF) sputtering. The latter showed a columnar growth, with a loose and porous microstructure. The columnar crystal growth of the former was inhibited, resulting in a more compact coating structure and a more uniform, flatter and smoother surface. Therefore, the structure and tribological properties of WS2 coating prepared via HiPIMS were investigated under different loads and frictional frequencies. Under low loads (up to 15 N), the coefficient of friction (COF) decreased with polishing wear mechanism. Under a high load of 20 N, the COF rapidly increased, the wear rate was the highest, and the wear mechanism changed from polishing to abrasive wear. At low frequencies (5 and 10 Hz), the coating had a low and stable COF, good wear resistance and the wear mechanism was abrasive wear. At high frequencies (≥15 Hz), the COF and wear rates rapidly increased and the wear mechanism changed from abrasive to adhesive wear and plastic fracture. However, the friction and wear rates were similar across different wear mechanisms.

Abstract Endothelial progenitor cells (EPCs) play a crucial role in maintaining vascular health and aiding in the repair of damaged blood vessels. However, the specific impact of EPCs-derived exosomes on vascular endothelial cell injury caused by lipopolysaccharide (LPS) remains inadequately understood. This study aims to explore the potential benefits of EPC-exosomes in mitigating LPS-induced vascular injury and to elucidate the underlying mechanism. Initially, EPCs were isolated from mouse peripheral blood, and their identity was confirmed through flow cytometry and immunocytochemistry. Subsequently, the exosomes derived from EPCs were identified using transmission electron microscopy (TEM) and western blot analysis. A sepsis model was induced by subjecting brain microvascular endothelial cells (BMECs) to LPS-induced injury. Both EPC and their exosomes demonstrated a significant increase in BMECs proliferation, reduced apoptosis, decreased levels of pro-inflammatory factors (TNF-α, IL-6, and caspase-3), and enhanced sprouting and angiogenesis of BMECs. Notable, the Exosomes demonstrated a more pronounced impact on these parameters. Furthermore, both EPCs and Exosomes exhibited significantly increased levels of miR-126a-5p, with the Exosomes showing a more substantial enhancement. These findings suggest that supplementing exosomal miR-126a-5p from EPCs can provide protective effects on BMECs, offering a potential therapeutic option for treating sepsis-induced microvascular endothelial cell injury.

Abstract The antitumor performance of PROteolysis-TArgeting Chimeras (PROTACs) is limited by its insufficient tumor specificity and poor pharmacokinetics. These disadvantages are further compounded by tumor heterogeneity, especially the presence of cancer stem-like cells, which drive tumor growth and relapse. Herein, we design a region-confined PROTAC nanoplatform that integrates both reactive oxygen species (ROS)-activatable and hypoxia-responsive PROTAC prodrugs for the precise manipulation of bromodomain and extraterminal protein 4 expression and tumor eradication. These PROTAC nanoparticles selectively accumulate within and penetrate deep into tumors via response to matrix metalloproteinase-2. Photoactivity is then reactivated in response to the acidic intracellular milieu and the PROTAC is discharged due to the ROS generated via photodynamic therapy specifically within the normoxic microenvironment. Moreover, the latent hypoxia-responsive PROTAC prodrug is restored in hypoxic cancer stem-like cells overexpressing nitroreductase. Here, we show the ability of region-confined PROTAC nanoplatform to effectively degrade BRD4 in both normoxic and hypoxic environments, markedly hindering tumor progression in breast and head-neck tumor models.

Abstract Introduction The phase III randomized KEYNOTE-522 trial demonstrated that pembrolizumab in combination with chemotherapy as neoadjuvant treatment followed by adjuvant pembrolizumab (pembrolizumab + chemotherapy) provided significant improvements in event-free survival (EFS) and overall survival (OS) for patients with high-risk early-stage triple-negative breast cancer (eTNBC). The objective was to assess the cost-effectiveness of pembrolizumab + chemotherapy compared to neoadjuvant chemotherapy alone (chemotherapy) in patients with high-risk eTNBC from a Hong Kong third-party payer perspective. Methods A multistate transition model with four health states (event-free), locoregional recurrence, distant metastases, and death) was developed to assess the lifetime medical costs and health outcomes (3% annual discount), along with incremental cost-effectiveness ratios (ICERs) using efficacy and safety data from the KEYNOTE-522 trial. The health state utilities were derived from KEYNOTE-522 Euro-QoL-five-dimension five-level questionnaire (EQ-5D-5L) data. Costs were expressed in 2022 Hong Kong dollars (HKD). Scenario and sensitivity analyses were performed to assess the robustness of results. Results Over a 32-year time horizon, base case results showed that pembrolizumab + chemotherapy was associated with a 3.42 year longer EFS and expected gains of 3.05 life years (LYs) and 2.45 quality-adjusted life years (QALYs) compared to chemotherapy. The resultant ICERs were HKD 135,200 per QALY gained and HKD 108,463 per LY gained, which were lower than the World Health Organization (WHO) cost-effectiveness threshold of three times gross domestic product (GDP) per capita for Hong Kong of HKD 1,171,308 per QALY. The one-way sensitivity analyses (OWSA) and probabilistic sensitivity analysis (PSA) showed the results were robust across various inputs and alternative scenarios. Conclusion On the basis of the analysis conducted for a 56-year-old cohort with high-risk eTNBC and assumptions in the model, pembrolizumab + chemotherapy represents a cost-effective proposition (as the ICER is approximately 35% of the GDP per capita in Hong Kong) for patients with high-risk eTNBC in Hong Kong.

The activation of spinal astrocytes accounts for opioid-induced hyperalgesia (OIH), but the underlying mechanisms remain elusive. The presence of astrocyte-neuron lactate shuttle (ANLS) makes astrocytes necessary for some neural function and communication. The aim of this study was to explore the role of ANLS in the occurrence and maintenance of OIH. After 7 days consecutive morphine injection, a mice OIH model was established and astrocytic pyruvate dehydrogenase kinase 4 (PDK4), phosphorylated pyruvate dehydrogenase (p-PDH) and accumulation of L-lactate was elevated in the spinal dorsal horn. Intrathecally administration of inhibitors of PDK, lactate dehydrogenase 5 and monocarboxylate transporters to decrease the supply of L-lactate on neurons was observed to attenuate hypersensitivity behaviors induced by repeated morphine administration and downregulate the expression of markers of central sensitization in the spinal dorsal horns. The astrocyte line and the neuronal line were co-cultured to investigate the mechanisms in vitro. In this study, we demonstrated that morphine-induced hyperalgesia was sustained by lactate overload consequent upon aberrant function of spinal ANLS. In this process, PDK-p-PDH-lactate axis serves a pivotal role, which might therefore be a new target to improve long-term opioid treatment strategy in clinical practice.

Abstract Background β-catenin, acting as the core effector of canonical Wnt signaling pathway, plays a pivotal role in controlling lineage commitment and the formation of definitive endoderm (DE) during early embryonic development. Despite extensive studies using various animal and cell models, the β-catenin-centered regulatory mechanisms underlying DE formation remain incompletely understood, partly due to the rapid and complex cell fate transitions during early differentiation. Results In this study, we generated new CTNNB1-/- human ES cells (hESCs) using CRISPR-based insertional gene disruption approach and systematically rescued the DE defect in these cells by introducing various truncated or mutant forms of β-catenin. Our analysis showed that a truncated β-catenin lacking both N- and C-terminal domains (ΔN148C) could robustly rescue the DE formation, whereas hyperactive β-catenin mutants with S33Y mutation or N-terminal deletion (ΔN90) had limited ability to induce DE lineage. Notably, the ΔN148C mutant exhibited significant nuclear translocation that was positively correlated with successful DE rescue. Transcriptomic analysis further uncovered that two weak β-catenin mutants lacking the C-terminal transactivation domain (CTD) activated primitive streak (PS) genes, whereas the hyperactive β-catenin mutants activated mesoderm genes. Conclusion Our study uncovered an unconventional regulatory function of β-catenin through weak transactivation, indicating that the levels of β-catenin activity determine the lineage bifurcation from mesendoderm into endoderm and mesoderm.

Abstract Recently, N6-methyladenosine (m6A) has aroused widespread discussion in the scientific community as a mode of RNA modification. m6A comprises writers, erasers, and readers, which regulates RNA production, nuclear export, and translation and is very important for human health. A large number of studies have found that the regulation of m6A is closely related to the occurrence and invasion of tumors, while the homeostasis and function of the tumor microenvironment (TME) determine the occurrence and development of tumors to some extent. TME is composed of a variety of immune cells (T cells, B cells, etc.) and nonimmune cells (tumor-associated mesenchymal stem cells (TA-MSCs), cancer-associated fibroblasts (CAFs), etc.). Current studies suggest that m6A is involved in regulating the function of various cells in the TME, thereby affecting tumor progression. In this manuscript, we present the composition of m6A and TME, the relationship between m6A methylation and characteristic changes in TME, the role of m6A methylation in TME, and potential therapeutic strategies to provide new perspectives for better treatment of tumors in clinical work.

Abstract Artificially extracted agricultural phenotype information exhibits high subjectivity and low accuracy, while the utilization of image extraction information is susceptible to interference from haze. Furthermore, the effectiveness of the agricultural image dehazing method used for extracting such information is limited due to unclear texture details and color representation in the images. To address these limitations, we propose AgriGAN (unpaired image dehazing via a cycle-consistent generative adversarial network) for enhancing the dehazing performance in agricultural plant phenotyping. The algorithm incorporates an atmospheric scattering model to improve the discriminator model and employs a whole-detail consistent discrimination approach to enhance discriminator efficiency, thereby accelerating convergence towards Nash equilibrium state within the adversarial network. Finally, by training with network adversarial loss + cycle consistent loss, clear images are obtained after dehazing process. Experimental evaluations and comparative analysis were conducted to assess this algorithm's performance, demonstrating improved accuracy in dehazing agricultural images while preserving detailed texture information and mitigating color deviation issues.

Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, is widely prescribed for hyperlipidemia management. Recent studies also showed that it has therapeutic potential in various liver diseases. However, its effects on hepatomegaly and liver regeneration and the involved mechanisms remain unclear. Here, the study showed that fenofibrate significantly promoted liver enlargement and regeneration post-partial hepatectomy in mice, which was dependent on hepatocyte-expressed PPARα. Yes-associated protein (YAP) is pivotal in manipulating liver growth and regeneration. We further identified that fenofibrate activated YAP signaling by suppressing its K48-linked ubiquitination, promoting its K63-linked ubiquitination, and enhancing the interaction and transcriptional activity of the YAP–TEAD complex. Pharmacological inhibition of YAP–TEAD interaction using verteporfin or suppression of YAP using AAV Yap shRNA in mice significantly attenuated fenofibrate-induced hepatomegaly. Other factors, such as MYC, KRT23, RAS, and RHOA, might also participate in fenofibrate-promoted hepatomegaly and liver regeneration. These studies demonstrate that fenofibrate-promoted liver enlargement and regeneration are PPARα-dependent and partially through activating the YAP signaling, with clinical implications of fenofibrate as a novel therapeutic agent for promoting liver regeneration.

Microorganisms play important roles in the remediation of contaminated soil. However, the relationship between the soil microbial communities and herbicide degradation remains unclear after applying green manure. The aim of this study was to investigate the effect of green manure on soil physicochemical properties, between acetochlor degradation and microbial communities. Adoption of pot experiments, the effects and mechanism of four fertilization treatments (CK: without green manure; GMV: Vicia villosa Roth; GML: Lolium perenne L.; GMR: Raphanus stativus L.) on the degradation of acetochlor were evaluated. Appling to Raphanus stativus L., acetochlor degraded in 5.82 days, which was 74.81 % higher than that of CK. Community differences in soil microbes were analysed using high-throughput sequencing. The predominant phyla of fungi were Ascomyocta, Mortierellomycota, Basidiomycota, unclassified_k_Fungi, and Chytridiomycota, which accounted for 85.01 %–116.46 % of the fungal OTUs. The green manure treatment showed higher abundance of Mortierella (9.54 %–13.05 %), diversity of saprotrophic fungi and symbiotic fungi and faster rate of degradation of acetochlor as compared to CK. In addition, soil properties such as soil total phosphorus (TP) and pH have significant effects on microorganisms. Fungal functional analysis revealed that the microorganisms associated with acetochlor biodegradation mainly belonged to Ascomycota and Glomeromycota. This study offers new insights into the relationship between soil properties and the environmental risks associated with the presence of pesticides in soil and the related mechanisms.

This study aimed to clarify the starch digestion characteristics and related physicochemical properties of the newly developed low-GI rice variety, Ditangliangyou 335 (D335), in comparison with two widely grown rice varieties, Xiangzaoxian 45 (X45) and Zhongzao 39 (Z39). The results showed that D335 had an active digestion duration (286 min) that was 101–190 % shorter, a glucose production rate (1.06 mg g−1 min−1) that was 57–73 % slower, and a total glucose production (303 mg g−1) that was 11–19 % less than X45 and Z39. These differences were attributable to the distinct starch physicochemical properties, including amylose content, amylose-to-amylopectin ratio, starch granule size, amylopectin chain length, and starch molar mass, as well as the different pasting properties of rice flour, such as pasting temperature and breakdown viscosity. These findings reveal the starch digestion characteristics and the key physicochemical properties that determine these characteristics in the low-GI rice variety D335.

This study estimated the incremental lifetime cancer risk (ILCR) of inorganic arsenic (iAs) from white rice ingestion in eight countries (China, Korea, Pakistan, Saudi Arabia, Thailand, Vietnam, Bangladesh, and Cambodia) in Asia by using data collected from published literature (n = 4857). ILCR of iAs exposure from white rice ingestion substantially varied with region, ranging from 0.37 to 13.46 per 10000 people, with an average of 6.12 per 10000 people. Bangladesh had the highest ILCR, followed by Cambodia, Vietnam, Thailand, China, Korea, Saudi Arabia, and Pakistan. Carcinogenic risks of iAs exposure from white rice ingestion in China, Korea, Thailand, Vietnam, Bangladesh, and Cambodia are at an unacceptable level (more than 1 per 10000 people). Linear regression analysis indicated that ingestion rate and inorganic arsenic content were the critical factors determining regional differences in carcinogenic risk of iAs exposure from white rice ingestion in Asia.

Objective The α-globin fusion gene between the HBA2 and HBAP1 genes, is clinically important in thalassemia screening because this fusion gene can cause severe hemoglobin (Hb) H disease when combined with α0 -thalassemia (α0 -thal). In this study, we evaluate the red blood cell parameters of α-thalassemia fusion gene in southern China.Method Study samples suspected of α-thalassemia fusion gene were collected and confirmed by PCR-sequencing from one medical lab center in southern China. Their genotypes and phenotypes were analyzed.Results A total of 266 cases of α-thalassemia fusion gene were confirmed in our lab from 2017 to 2023, most of them were from Hainan province (169 cases) and Huadu district of Guangzhou (21 cases), the nationality of 143 cases from Hainan was identified, with 71.3% (102/143) being from the Li minority. The Hb, MCV, MCH for αα/(αα)fusion in adult males were 143.5±11.83g/L, 81.51±4.39 fl, and 26.26±1.29 pg, respectively; and in females, they were 126.69±12.89 g/L, 80.10±4.05 fl, 25.8±2.04 pg, respectively. All 12 cases (αα) Fusion/ --SEA showed anemia with decreased Hb, MCV and MCH.Conclusion The carriers of α-globin fusion gene heterozygotes are clinically silent and exhibit an α+ phenotype. Individuals with (αα)Fusion/--SEA show apparent anemia. This α-globin fusion gene is relatively common in southern China, specifically among the Li minority of Hainan province. Therefore, it should be taken into account for genetic counseling purposes.

Rice breeders have developed numerous hybrid rice varieties with high yield and improved quality over the years. However, limited information is available on the stability of quality traits in high-quality rice. This study determined the stability of quality traits in two high-quality hybrid rice varieties, Zhuliangyou 570 (ZLY570) and Huazheyou 261 (HZY261), across different ecological regions and agronomic practices through on-farm research and field experiments. The on-farm research was conducted across nine provinces in southern China in 2021–2023, and field experiments with two sowing dates and six nitrogen treatments were performed in Hunan Province in 2022 and 2023. Results indicated that in both on-farm research and field experiments, both varieties exhibited a high coefficient of variation (CV) in chalky grain rate and chalkiness degree, followed by head rice rate, amylose and protein contents, traits including brown and milled rice rates, and length-to-width ratio revealed a low CV. The chalky grain rate and chalkiness degree of both varieties displayed poor stability, followed by head rice rate and amylose content. In contrast, brown and milled rice rates, length-to-width ratio, and protein content demonstrated high stability in the genotype plus genotype × environment interaction biplot analysis. However, the maximum value of chalky grain rate and chalkiness degree were only 8.43 % and 1.83 % for ZLY570, and 9.12 % and 2.05 % for HZY261, respectively. Both varieties revealed a high range (R) in head rice rate and amylose content, but a low R in protein content. Furthermore, the head rice rate and amylose content varied widely, while protein content showed narrower variability. These results suggest that high-quality hybrid rice exhibits poor stability in terms of head rice rate and amylose content. In contrast, it demonstrates relatively high stability in brown and milled rice rates, length-to-width ratio, chalky grain rate, chalkiness degree, and protein content.

The continuous expansion and development of anthropogenic activities pose considerable threats to the habitats of myriad species. Therefore, exploring how to protect and optimize species’ habitats to achieve harmony between humans and nature is particularly important. As a paradise for wildlife, Poyang Lake is the habitat and breeding ground for birds, fish, and other aquatic organisms. In this study, adopting a multi-level perspective of ‘point-line-area’, we had an appliance for habitat conservation by constructing an ecological security pattern (ESP) in the Poyang Lake Ecoregion (PYLE). We produced land use and land cover from 2000 to 2040 using the random forest and cellular automata-Markov model. Combining morphological spatial pattern analysis, landscape pattern index, and Linkage Mapper, we constructed a long-term ESP in the PYLE considering habitat protection. The spatiotemporal dynamics of ESP were compared and analyzed. The results show that PYLE's rapid economic development led to extensive urban growth, encroaching on surrounding bare land, which could undermine local species’ survival. Based on PYLE's predicted ESP in 2040, we propose an optimized ‘one area, two zones, and multiple points’ scheme to prioritize habitat protection. This comprehensive study provides innovative ideas and novel insights for future research and policy formulation in habitat protection.

The starch digestion properties of cooked rice are associated with the chemical compositions of the rice grain. However, limited information is available on the chemical composition governing starch digestion properties in high-amylose rice. To overcome this knowledge gap, correlation plot analysis and partial correlation analysis were utilized to assess the correlations between active digestion duration, total glucose production, and glucose production rate of cooked rice to amylose, amylopectin, and protein content of rice grains throughout 17 high-amylose varieties. The correlation plot analysis identified significant positive or negative linkages between total glucose production and the glucose production rate of cooked rice with grain amylose, amylopectin, and protein content. Nevertheless, partial correlation analysis only characterized a significant positive correlation between glucose production rate and grain amylopectin content. The findings of this study indicate that grain amylopectin content rather than grain amylose or protein content is critical for the determination of the rate of starch digestion in high-amylose rice.

ABSTRACTDouble minutes (DMs), extrachromosomal gene fragments found within certain tumors, have been noted to carry onco- and drug resistance genes contributing to tumor pathogenesis and progression. After screening for SUMO-related molecule expression within various tumor sample and cell line databases, we found that SUMO-conjugating enzyme UBC9 has been associated with genome instability and tumor cell DM counts, which was confirmed both in vitro and in vivo. Karyotyping determined DM counts post-UBC9 knockdown or SUMOylation inhibitor 2-D08, while RT-qPCR and Western blot were used to measure DM-carried gene expression in vitro. In vivo, fluorescence in situ hybridization (FISH) identified micronucleus (MN) expulsion. Western blot and immunofluorescence staining were then used to determine DNA damage extent, and a reporter plasmid system was constructed to detect changes in homologous recombination (HR) and non-homologous end joining (NHEJ) pathways. Our research has shown that UBC9 inhibition is able to attenuate DM formation and lower DM-carried gene expression, in turn reducing tumor growth and malignant phenotype, via MN efflux of DMs and lowering NHEJ activity to increase DNA damage. These findings thus reveal a relationship between heightened UBC9 activity, increased DM counts, and tumor progression, providing a potential approach for targeted therapies, via UBC9 inhibition.

BackgroundAcute myocardial infarction (AMI) represents the gravest manifestation of ischemic heart disease, with the primary cause of mortality and morbidity worldwide. Although timely and accurate diagnosis of AMI is crucial in clinical practice, they are impeded by the limitation of current biomarkers. We aimed to explore the potential predictive value of two novel long non-coding RNA (lncRNA) HCG15 and Morrbid in AMI diagnosis and prognosis.MethodWe measured the lncRNA levels in the blood samples of 412 AMI patients and 111 healthy volunteers with the RT-PCR method. Receiver operating characteristic (ROC) curves were plotted to access the diagnostic value of selected lncRNAs. Restricted cubic splines (RCS) and the Kaplan-Meier method were utilized to examine the predictive value of the selected lncRNAs in AMI diagnosis.ResultROC curves identified an acceptable diagnostic value of HCG15 and Morrbid (AUC for HCG15: 0.937; AUC for Morrbid: 0.940). RCS and Kaplan-Meier analysis revealed the cut-off value of 3.6 for HCG15 and 4.0 for Morrbid have a good predictive value in MACCE within 12 months once AMI was diagnosed (p-value for HCG15: p = 0.025; p-value for Morrbid: p < 0.0001).ConclusionHCG15 and Morrbid were confirmed as promising lncRNA biomarkers for both diagnosis and prognosis of AMI in this study. Additionally, their importance of application in real-world clinical practice and underlying mechanisms in AMI diagnosis and prognosis remain to be explored.

High-quality land-use/land-cover mapping with optical remote sensing images yet presents significant work. Even though fully convolutional semantic segmentation models have recently contributed to popular solutions, the lack of annotation data may lead to severe degradations in their inference performance. Besides, the category confusion in high-resolution representations will further exacerbate the adverse effects. In this paper, we propose a category-sensitive semi-supervised semantic segmentation framework to address these weaknesses by employing massive unlabeled data. With the perturbations from adopted hybrid data augmentation structures, we first focus on the output space and execute regularization constraints to learn category-specific discriminative features. It is formulated with a consistency self-training procedure where a dynamic class-balanced threshold selection scheme is proposed to provide high-confident pseudo supervisions for each category. In addition, we introduce pixel-wise contrastive learning on the common embedding space from both labeled and unlabeled data domains to further facilitate the semantic dependencies among category features, in which the reliable labels are leveraged as guidance for pixel sample selection. We verify the proposed framework on two benchmark land-use/land-cover datasets, and the experimental results demonstrate its competitive performance to other state-of-the-art semi-supervised methods.

OBJECTIVES:. Monocytes are plastic cells that assume different polarization states that can either promote inflammation or tissue repair and inflammation resolution. Polarized monocytes are partially defined by their transcriptional profiles that are influenced by environmental stimuli. The airway monocyte response in pediatric acute respiratory distress syndrome (PARDS) is undefined. To identify differentially expressed genes and networks using a novel transcriptomic reporter assay with donor monocytes exposed to the airway fluid of intubated children with and at-risk for PARDS. To determine differences in gene expression at two time points using the donor monocyte assay exposed to airway fluid from intubated children with PARDS obtained 48–96 hours following initial tracheal aspirate sampling. DESIGN:. In vitro pilot study carried out using airway fluid supernatant. SETTING:. Academic 40-bed PICU. PARTICIPANTS:. Fifty-seven children: 44 children with PARDS and 13 children at-risk for PARDS. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. We performed bulk RNA sequencing using a transcriptomic reporter assay of monocytes exposed to airway fluid from intubated children to discover gene networks differentiating PARDS from at-risk for PARDS and those differentiating mild/moderate from severe PARDS. We also report differences in gene expression in children with PARDS 48–96 hours following initial tracheal aspirate sampling. We found that interleukin (IL)-10, IL-4, and IL-13, cytokine/chemokine signaling, and the senescence-associated secretory phenotype are upregulated in monocytes exposed to airway fluid from intubated children with PARDS compared with those at-risk for PARDS. Signaling by NOTCH, histone deacetylation/acetylation, DNA methylation, chromatin modifications (B-WICH complex), and RNA polymerase I transcription and its associated regulatory apparatus were upregulated in children with PARDS 48–96 hours following initial tracheal aspirate sampling. CONCLUSIONS:. We identified gene networks important to the PARDS airway immune response using bulk RNA sequencing from a monocyte reporter assay that exposed monocytes to airway fluid from intubated children with and at-risk for PARDS. Mechanistic investigations are needed to validate our findings.

Ascorbic acid (AsA) is one of the most abundant natural antioxidants, and it is an important indicator of the nutritional value of cucumber fruit. The aim of this study was to elucidate the regulatory mechanism affecting AsA metabolism in cucumber fruit. In this study, the AsA content in the fruit of two cucumber cultivars (H28 and H105) was significantly higher in the exocarp and endocarp than in the mesocarp. To clarify the regulation of AsA in cucumber fruit, the transcriptomes of three fruit tissues (i.e., the exocarp, mesocarp, and endocarp) of two cucumber cultivars (H28 and H105) were sequenced. Transcriptomic profiling combined with transcription factors (TFs) and correlation analysis were performed to reveal that three genes, including CsaV3_5G014110 (phosphomannomutase, PMM), CsaV3_2G004170 (GDP-mannose-3′, 5′-epimerase, GME) and CsaV3_5G006680 (dehydroascorbate reductase, DHAR), were expressed at higher level in the exocarp and endocarp than in the mesocarp. In both two cultivars, CsaV3_4G028360 (ethylene-responsive transcription factor, ERF) was negatively correlated with PMM and GME, and positively correlated with DHAR. CsaV3_6G042110 (ethylene-responsive transcription factor, ERF) was positively correlated with PMM and GME, and negatively correlated with DHAR. CsaV3_6G032360 (mitogen-activated protein kinase, MAPK) as positively correlated with PMM, GME and DHAR. These six genes are considered the key candidate genes for further research. This study provides insight for further study on the regulation of AsA biosynthesis in cucumber fruit and provide potential candidate genes for future genetic improvement of cucumber germplasm with enhanced AsA accumulation.

BackgroundKawasaki disease (KD) is an acute systemic vasculitis that can lead to acquired heart disease in children mostly from in developed countries. The previous research showed that B cells in KD patients underwent a profound change in both the cell numbers and types after intravenous immunoglobulin (IVIG) therapy.MethodsWe performed the single-cell RNA-sequencing for the peripheral blood mononuclear cells (PBMCs) from three febrile patients and three KD patients to investigate the possible mechanism underlying B cell developmental dysfunction in KD. The pseudo-time analysis was employed to study the developmental trajectories of the PBMCs in febrile control and KD patients.ResultsOverall single-cell expression profiles show that the biological processes of immunity, B cell activation pathway and their related biological entities are repressed in KD patients before IVIG treatment compared to febrile patient and KD patients after IVIG treatment. The differentially expressed gene analyses further demonstrate that B cell signaling pathway is downregulated in B cells and plasma blast cells of KD patients before treatment while cell cycle genes and MYC gene are upregulated in dendritic cells (DCs) and hematopoietic stem and progenitor cells (HSPCs) of KD patients before treatment. The biological process of immune response is upregulated in the HSPCs of KD patients before treatment in our dataset while the biological process of inflammatory response is upregulated in the HSPCs of KD patients before treatment in GSE168732 dataset. Single-cell trajectory analyses demonstrate that KD patients before treatment have a shortened developmental path in which B cells and T cells are failed to differentiate into separate lineages. HSPD1 and HSPE1 genes show an elevated expression level in the early cell development stage of KD patients before treatment accompanied with the repression of MYC, SPI1, MT2A and UBE2C genes. Our analyses of all B cells from KD patients before treatment show most of B cells are arrested in a transitional state with an ill developmental path compared with febrile patients and KD patients after treatment.ConclusionOur results indicate that the immune premature HSPCs accompanied with the abnormal expression dynamics of cell cycle and SPI1 genes are the mechanism underlying B cell developmental dysfunction in KD patients.

Obesity-induced chronic inflammation exacerbates multiple types of tissue/organ deterioration and stem cell dysfunction; however, the effects on skeletal tissue and the underlying mechanisms are still unclear. Here, we show that obesity triggers changes in the microRNA profile of macrophage-secreted extracellular vesicles, leading to a switch in skeletal stem/progenitor cell (SSPC) differentiation between osteoblasts and adipocytes and bone deterioration. Bone marrow macrophage (BMM)-secreted extracellular vesicles (BMM-EVs) from obese mice induced bone deterioration (decreased bone volume, bone microstructural deterioration, and increased adipocyte numbers) when administered to lean mice. Conversely, BMM-EVs from lean mice rejuvenated bone deterioration in obese recipients. We further screened the differentially expressed microRNAs in obese BMM-EVs and found that among the candidates, miR-140 (with the function of promoting adipogenesis) and miR-378a (with the function of enhancing osteogenesis) coordinately determine SSPC fate of osteogenic and adipogenic differentiation by targeting the Pparα-Abca1 axis. BMM miR-140 conditional knockout mice showed resistance to obesity-induced bone deterioration, while miR-140 overexpression in SSPCs led to low bone mass and marrow adiposity in lean mice. BMM miR-378a conditional depletion in mice led to obesity-like bone deterioration. More importantly, we used an SSPC-specific targeting aptamer to precisely deliver miR-378a-3p-overloaded BMM-EVs to SSPCs via an aptamer-engineered extracellular vesicle delivery system, and this approach rescued bone deterioration in obese mice. Thus, our study reveals the critical role of BMMs in mediating obesity-induced bone deterioration by transporting selective extracellular-vesicle microRNAs into SSPCs and controlling SSPC fate.

Abstract In order to identify the key antioxidant defense systems used to cope with high-temperature stress in rice leaf chloroplasts following biochar supplementation, the present study compared the expression levels of chloroplast proteins related to antioxidant defense in high-temperature stressed rice leaves between without (C0) and with biochar supplementation (C40; 40 g biochar kg–1 soil). A total of sixteen differentially expressed antioxidant chloroplastic proteins were identified. Among them, three antioxidant enzyme proteins and eight thioredoxin proteins were 62–123% and 37–225% higher under the C40 treatment compared to C0, respectively. These results suggest that both antioxidant enzymes and the thioredoxin system are central to the biochar-mediated protection of rice leaves exposed to high-temperature stress.

For over two decades, the development of B-cell lymphoma-2 (Bcl-2) family therapeutics has primarily focused on anti-apoptotic proteins, resulting in the first-in-class drugs called BH3 mimetics, especially for Bcl-2 inhibitor Venetoclax. The pro-apoptotic protein Bcl-2-associated X protein (BAX) plays a crucial role as the executioner protein of the mitochondrial regulated cell death, contributing to organismal development, tissue homeostasis, and immunity. The dysregulation of BAX is closely associated with the onset and progression of diseases characterized by pathologic cell survival or death, such as cancer, neurodegeneration, and heart failure. In addition to conducting thorough investigations into the physiological modulation of BAX, research on the regulatory mechanisms of small molecules identified through biochemical screening approaches has prompted the identification of functional and potentially druggable binding sites on BAX, as well as diverse all-molecule BAX modulators. This review presents recent advancements in elucidating the physiological and pharmacological modulation of BAX and in identifying potentially druggable binding sites on BAX. Furthermore, it highlights the structural and mechanistic insights into small-molecule modulators targeting diverse binding surfaces or conformations of BAX, offering a promising avenue for developing next-generation apoptosis modulators to treat a wide range of diseases associated with dysregulated cell death by directly targeting BAX.

The rapid development of 5G/6G and AI enables an environment of Internet of Everything (IoE) which can support millions of connected mobile devices and applications to operate smoothly at high speed and low delay. However, these massive devices will lead to explosive traffic growth, which in turn cause great burden for the data transmission and content delivery. This challenge can be eased by sinking some critical content from cloud to edge. In this case, how to determine the critical content, where to sink and how to access the content correctly and efficiently become new challenges. This work focuses on establishing a highly efficient content delivery framework in the IoE environment. In particular, the IoE environment is re-constructed as an end-edge-cloud collaborative system, in which the concept of digital twin is applied to promote the collaboration. Based on the digital asset obtained by digital twin from end users, a content popularity prediction scheme is firstly proposed to decide the critical content by using the Temporal Pattern Attention (TPA) enabled Long Short-Term Memory (LSTM) model. Then, the prediction results are input for the proposed caching scheme to decide where to sink the critical content by using the Reinforce Learning (RL) technology. Finally, a collaborative routing scheme is proposed to determine the way to access the content with the objective of minimizing overhead. The experimental results indicate that the proposed schemes outperform the state-of-the-art benchmarks in terms of the caching hit rate, the average throughput, the successful content delivery rate and the average routing overhead.

Ovarian cancer is a prevalent malignancy among women, often associated with a poor prognosis. Post-translational modifications (PTMs), particularly O-GlcNAcylation, have been implicated in the progression of ovarian cancer. Emerging evidence indicates that dysregulation of O-GlcNAcylation contributes to the initiation and malignant progression of ovarian cancer. This review discusses the potential role of O-GlcNAcylation in ovarian tumorigenesis, with a focus on its regulation of various cellular signaling pathways, including p53, RhoA/ROCK/MLC, Ezrin/Radixin/Moesin (ERM), and β-catenin. This review also emphasizes the O-GlcNAcylation of critical proteins in ovarian cancer, such as SNAP-23, SNAP-29, E-cadherin, and calreticulin. Additionally, the potential of O-GlcNAcylation to enhance immunotherapy for ovarian cancer patients is explored. Several compounds targeting OGT and OGA in ovarian cancer are also highlighted. Targeting the dynamic and versatile nature of O-GlcNAcylation could undoubtedly contribute to more effective treatments and improved outcomes for ovarian cancer patients.

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease. Body mass index (BMI) is the most used obesity index but has important limitations. The weight-adjusted waist index (WWI) is a novel obesity metric and accurately reflects body composition. We explored the association of WWI with all-cause and cardiovascular disease (CVD) mortality in MASLD.MethodsAdult participants with MASLD were included from NHANES 1999-2018. WWI was calculated by dividing the waist circumference (WC) by the square root of body weight. MASLD was diagnosed by the presence of hepatic steatosis and at least one cardiometabolic risk factor in the absence of other causes of steatosis. A fatty liver index ≥60 suggested the presence of hepatic steatosis. Mortality data was obtained by prospectively linking to the National Death Index. Multivariate Cox proportional hazards regression analyses were used to explore these associations and multiple adjustment models were constructed including crude, partial, and fully adjusted models.ResultsAfter adjusting for all covariates including BMI, WWI remained positively and linearly associated with all-cause and CVD mortality in MASLD (hazard ratios [HR] 1.247 and 1.218, respectively). Higher WWI was associated with a significantly increased risk of mortality (both p for trend

BackgroundExposure to occupational metallic mixtures has a potential impact on olfactory function. However, research evidence is limited on the potential impact of exposure to metallic mixtures and olfactory dysfunction. Furthermore, the coal dust generated contains multiple various metals during coal mining, and no study yet has focus on the olfactory dysfunction of coal miners.ObjectivesIn this study, we evaluate the association between urinary metallic mixtures and olfactory function in coal miners, while also exploring the potential applicability of plasma olfactory marker protein (OMP) as a biomarker for assessing olfaction.MethodsFrom July to October 2023, coal workers from seven different coal mining enterprises were recruited for the survey when they come for the employee health checkup. Ultimately, 376 participants were met the inclusion criteria and, respectively, determined with the concentrations of urine (16 metals) and plasma (OMP). Meanwhile, applying UPSIT to access their olfactory function. Binary logistic regression and restricted cubic spline (RCS) model were used to estimate the association of individual metals with olfactory function. Bayesian kernel machine regression (BKMR) and Quantile g-computation (QG-C) regression were employed to assess the overall association between metal mixtures and olfactory function and identify the major contributing elements.ResultsIn a single-metal model, two metals in urine were found to be significantly associated with olfactory function. RCS analysis further revealed that the association between Iron (Fe) and olfactory function was linear, while Lead (Pb) exhibited a non-linear. The BKMR model demonstrated a significant positive association between metal mixture concentration and olfactory function. Combined QG-C regression analysis suggested that metals Cr, Fe, Se, Sb, and Pb could impact the performance of the olfactory test (UPSIT), with Pb being identified as the most influential contributor. The correlation between plasma OMP protein levels and urinary metal concentrations was weak.ConclusionMultiple metals are associated with olfactory function in the coal miners. A significant positive association was observed between metal mixture concentrations and olfactory function, with Pb being the most important contributor. In this study, plasma OMP has not been demonstrated to serve as a biomarker for olfactory function.

Arable land is the fundamental guarantee of agricultural production, and accessing accurate arable land information is particularly crucial. A novel deep learning model named CNX-eMLP with ConvNeXt as the backbone and an enhanced Multilayer Perceptron (eMLP) as the decoder was proposed for arable land extraction. The model was employed to extract arable land using high-resolution satellite imagery in a case study at Pengxi County of Southwest China and compared its performance with six deep learning models, a machine learning-based algorithm, and SinoLC-1. The study results show the CNX-eMLP significantly achieved the highest accuracy, with MIoU and OA of 75.21 and 87.9, highlighting a trade-off between computational complexity and accuracy. The CNX-eMLP model reveals arable land is predominantly found in low-altitude areas (below 400 m), with most plots being 0-5 hectares. The study presents an efficient and feasible method for accurate high-resolution remote sensing monitoring of arable land parcels in hilly regions.

Lewy body disease (LBD), one of the most common neurodegenerative diseases (NDDs), is characterized by excessive accumulation of α-synuclein (α-syn) in neurons. In recent years, environmental factors such as exposure to herbicides and pesticides have been attributed to the development of this condition. While majority of the studies on neurotoxic effects of paraquat (PQ) have focused on α-syn-mediated neuronal damage in the early stages of α-syn accumulation in neurons, efforts to explore the key target for α-syn degradation are limited. Recent research has suggested that histone deacetylase 6 (HDAC6) might possibly regulate amyloid clearance, and that the metabolism of compounds in neurons is also directly affected by axonal transport in neurons. Dynein predominantly mediates reverse transportation of metabolites and uptake of signal molecules and other compounds at the end of axons, which is conducive to the reuse of cell components. However, the role of interaction of dynein with HDAC6 in metabolites transport is still unclear. Therefore, this study aimed to investigate the role of HDAC6 in α-syn accumulation/clearance in neurons and the associated possible influencing factors. The results revealed that HDAC6 could transport ubiquitinated α-syn, bind to dynein, form an aggresome, and relocate to the center of the microtubule tissue, ultimately reducing abnormal accumulation of α-syn. However, PQ treatment resulted in HDAC6 upregulation, causing abnormal aggregation of α-syn. Taken together, these findings indicated that PQ exposure caused abnormal accumulation of α-syn and decreased effective degradation of α-syn by HDAC6-mediated aggresome-autophagy-lysosome pathway.

Background: Studies reported an association between rheumatoid arthritis and Diabetes mellitus. We sought to assess the causal association between rheumatoid arthritis and Diabetes mellitus risk using a two-way two-sample Mendelian randomization (MR) analysis. Methods: Data on Diabetes mellitus and rheumatoid arthritis were obtained from the GWAS genome-wide database, and the MR method was used to explore the bidirectional causal association, the inverse variance weighted (IVW) method was used as the primary analysis method, and sensitivity analysis was performed. Results: IVW results and MR-Egger method indicate that there is a significant correlation between Diabetes mellitus and rheumatoid arthritis (IVW: P = 0.002, OR = 1.057, 95%CI: 1.02–1.096, MR-Egger: P = 0.037, OR = 1.096, 95%CI: 1.006–1.194), MR-Egger intercept analysis shows that the P-value is 0.362 (>0.05), IVW results showed a significant association between rheumatoid arthritis and Diabetes mellitus (IVW: P = 2.65 × 10–9, OR = 1.797, 95%CI: 1.481–2.180), MR-Egger intercept analysis shows that the P-value is 0.221 (>0.05). Conclusion: The results confirm that Diabetes mellitus and rheumatoid arthritis have a two-way causal chain, and it is necessary to strengthen bidirectional surveillance.

ABSTRACT The Changle goose (CLG), a Chinese indigenous breed, is celebrated for its adaptability, rapid growth, and premium meat quality. Despite its agricultural value, the exploration of its genomic attributes has been scant. Our study entailed whole‐genome resequencing of 303 geese across CLG and five other Chinese breeds, revealing distinct genetic diversity metrics. We discovered significant migration events from Xingguo gray goose to CLG and minor gene flow between them. We identified genomic regions through selective sweep analysis, correlating with CLG's unique traits. An elevated inbreeding coefficient in CLG, alongside reduced heterozygosity and rare single nucleotide polymorphisms (RSNPs), suggests a narrowed genetic diversity. Genomic regions related to reproduction, meat quality, and growth were identified, with the GATA3 gene showing strong selection signals for meat quality. A non‐synonymous mutation in the Sloc2a1 gene, which is associated with reproductive traits in the CLG, exhibited significant differences in allelic frequency. The roles of CD82, CDH8, and PRKAB1 in growth and development, alongside FABP4, FAF1, ESR1, and AKAP12 in reproduction, were highlighted. Additionally, Cdkal1 and Mfsd14a may influence meat quality. This comprehensive genetic analysis underpins the unique genetic makeup of CLG, providing a basis for its conservation and informed breeding strategies.

Abstract Cardiac hypertrophy is a key factor driving heart failure (HF), yet its pathogenesis remains incompletely elucidated. Mettl1‐catalyzed RNA N7‐methylguanosine (m7G) modification has been implicated in ischemic cardiac injury and fibrosis. This study aims to elucidate the role of Mettl1 and the mechanism underlying non‐ischemic cardiac hypertrophy and HF. It is found that Mettl1 is upregulated in human failing hearts and hypertrophic murine hearts following transverse aortic constriction (TAC) and Angiotensin II (Ang II) infusion. YY1 acts as a transcriptional factor for Mettl1 during cardiac hypertrophy. Mettl1 knockout alleviates cardiac hypertrophy and dysfunction upon pressure overload from TAC or Ang II stimulation. Conversely, cardiac‐specific overexpression of Mettl1 results in cardiac remodeling. Mechanically, Mettl1 increases SRSF9 expression by inducing m7G modification of SRSF9 mRNA, facilitating alternative splicing and stabilization of NFATc4, thereby promoting cardiac hypertrophy. Moreover, the knockdown of SRSF9 protects against TAC‐ or Mettl1‐induced cardiac hypertrophic phenotypes in vivo and in vitro. The study identifies Mettl1 as a crucial regulator of cardiac hypertrophy, providing a novel therapeutic target for HF.

Like all coronaviruses, infectious bronchitis virus, the causative agent of infectious bronchitis in chickens, exhibits a high mutation rate. Adaptive mutations that arise during the production of live attenuated vaccines against IBV often decrease virulence. The specific impact of these mutations on viral pathogenicity, however, has not been fully elucidated. In this study, we identified a mutation at the 3' end of the S gene in an IBV strain that was serially passaged in chicken embryos, and showed that this mutation resulted in a 9-aa truncation of the cytoplasmic tail (CT) of the S protein. This phenomenon of CT truncation has previously been observed in the production of attenuated vaccines against other coronaviruses such as the porcine epidemic diarrhea virus. We next discovered that the 9-aa truncation in the S protein CT resulted in the loss of the endoplasmic-reticulum-retention signal (KKSV). Rescue experiments with recombinant viruses confirmed that the deletion of the KKSV motif impaired the localization of the S protein to the endoplasmic-reticulum-Golgi intermediate compartment (ERGIC) and increased its expression on the cell surface. This significantly reduced the incorporation of the S protein into viral particles, impaired early subgenomic RNA and protein synthesis, and ultimately reduced viral invasion efficiency in CEK cells. In vivo experiments in chickens confirmed the reduced pathogenicity of the mutant IBV strains. Additionally, we showed that the adaptive mutation altered the TRS-B of ORF3 and impacted the transcriptional regulation of this gene. Our findings underscore the significance of this adaptive mutation in the attenuation of IBV infection and provide a novel strategy for the development of live attenuated IBV vaccines.

Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS) is a widely utilized technique for in vivo pharmaceutical analysis. Ionization interference within electrospray ion source, occurring between drugs and metabolites, can lead to signal variations, potentially compromising quantitative accuracy. Currently, method validation often overlooks this type of signal interference, which may result in systematic errors in quantitative results without matrix-matched calibration. In this study, we conducted an investigation using ten different groups of drugs and their corresponding metabolites across three LC-ESI-MS systems to assess the prevalence of signal interference. Such interferences can potentially cause or enhance nonlinearity in the calibration curves of drugs and metabolites, thereby altering the relationship between analyte response and concentration for quantification. Finally, we established an evaluation scheme through a step-by-step dilution assay and employed three resolution methods: chromatographic separation, dilution, and stable labeled isotope internal standards correction. The above strategies were integrated into the method establishment process to improve quantitative accuracy.

Background: China produces and consumes a large amount of neonicotinoids. A non-negligible exposure to neonicotinoids might occur for Chinese pregnant women, but relevant data remain limited. Objective: To investigate the exposure to neonicotinoids by urinary biomonitoring in pregnant women from Wenzhou City, East China. Methods: We selected 432 pregnant women in Wenzhou City in 2022. A total of eight parent neonicotinoids and four metabolites were determined in single spot urine by liquid chromatography coupled to mass spectrometry. Basic characteristics, physical activity, pre-pregnant body mass index, and intake of drinking water and food were investigated by the questionnaire. Health risk was assessed by hazard quotient (HQ) and hazard index (HI) based on human safety thresholds derived from different health endpoints. Results: Neonicotinoids and their metabolites in urine had a detection frequency between 0 % and 80.1 %. At least one neonicotinoid or metabolite was detected in 93.5 % of urine samples. Except for clothianidin (51.2 %) and N-desmethyl-acetamiprid (80.1 %), the detection frequencies of other neonicotinoids and metabolites ranged from 0 % to 43.8 %. The summed concentrations of all neonicotinoids and their metabolites ranged from

Bile acid homeostasis is critical to human health. Low-level exposure to antibiotics has been suggested to potentially disrupt bile acid homeostasis by affecting gut microbiota, but relevant data are still lacking in humans, especially for the level below human safety threshold. We conducted a cross-sectional study in 4247 Chinese adults by measuring 34 parent antibiotics and their metabolites from six common categories (i.e., tetracyclines, qinolones, macrolides, sulfonamides, phenicols, and lincosamides) and ten representative bile acids in fasting morning urine using liquid chromatography coupled to mass spectrometry. Daily exposure dose of antibiotics was estimated from urinary concentrations of parent antibiotics and their metabolites. Urinary bile acids and their ratios were used to reflect bile acid homeostasis. The estimated daily exposure doses (EDED) of five antibiotic categories with a high detection frequency (i.e., tetracyclines, qinolones, macrolides, sulfonamides, and phenicols) were significantly associated with urinary concentrations of bile acids and decreased bile acid ratios in all adults and the subset of 3898 adults with a cumulative ratio of antibiotic EDED to human safety threshold of less than one. Compared to a negative detection of antibiotics, the lowest EDED quartiles of five antibiotic categories and four individual antibiotics with a high detection frequency (i.e., ciprofloxacin, ofloxacin, trimethoprim, and florfenicol) in the adults with a positive detection of antibiotics had a decrease of bile acid ratio between 6.6% and 76.6%. Except for macrolides (1.2×102 ng/kg/day), the medians of the lowest EDED quartile of antibiotic categories and individual antibiotics ranged from 0.32 ng/kg/day to 10 ng/kg/day, which were well below human safety thresholds. These results suggested that low-level antibiotic exposure could disrupt bile acid homeostasis in adults and existing human safety thresholds may be inadequate in safeguarding against the potential adverse health effects of low-level exposure to antibiotics.

Abstract Network function virtualization (NFV) technology deploys network functions as software functions on a generalised hardware platform and provides customised network services in the form of service function chain (SFC), which improves the flexibility and scalability of network services and reduces network service costs. However, irrational resource allocation during service function chain mapping will cause problems such as low resource utilisation, long service request processing time and low mapping rate. To address the unreasonable problem of service mapping resource allocation, an improved service function chain mapping resource allocation method (SA3C) based on the Asynchronous advantageous action evaluation algorithm (A3C) is proposed. This study proposes an SFC mapping model and a mathematical model for joint allocation, which modeled the minimization of processing time as a Markov process. The main network was trained and multiple sub‐networks were generated in parallel using the ternary and deep reinforcement learning algorithm A3C, with the goal of identifying the optimal resource allocation strategy. The experimental simulation results show that compared with the Actor‐Critic (AC) and Policy Gradient (PG) methods, SA3C algorithm can improve the resource utilisation by 9.85%, reduce the total processing time by 10.72%, and improve the mapping rate by 6.72%, by reasonably allocating node computational resources and link bandwidth communication resources.

Abstract A national distribution of secondary forest age (SFA) is essential for understanding the forest ecosystem and carbon stock in China. While past studies have mainly used various change detection algorithms to detect forest disturbance, which cannot adequately characterize the entire forest landscape. This study developed a data-driven approach for improving performances of the Vegetation Change Tracker (VCT) and Continuous Change Detection and Classification (CCDC) algorithms for detecting the establishment of forest stands. An ensemble method for mapping national-scale SFA by determining the establishment time of secondary forest stands using change detection algorithms and dense Landsat time series was proposed. A dataset of national secondary forest age for China (SFAC) for 1 to 34 and with a 30-m spatial resolution was produced from the optimal ensemble model. This dataset provides national, continuous spatial SFA information and can improve understanding of secondary forests and the estimation of forest carbon storage in China.