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Abstract Cuproptosis is characterized by lipoylated protein aggregation and loss of iron–sulfur (Fe–S) proteins, which are crucial for a wide range of important cellular functions, including DNA replication and damage repair. Sirt2 and sirt4 are lipoamidases that remove the lipoyl moiety from lipoylated proteins using nicotinamide adenine dinucleotide (NAD+) as a cofactor. However, to date, it is not clear whether nicotinamide mononucleotide (NMN), a precursor of NAD+, affects cellular sensitivity to cuproptosis. Therefore, in the current study, cuproptosis was induced by the copper (Cu) ionophore elesclomol (Es) in HeLa cells. It was also found that Es/Cu treatment increased cellular DNA damage level. On the other hand, NMN treatment partially rescued cuproptosis in a dose-dependent manner, as well as reduced cellular DNA damage level. In addition, NMN upregulated the expression of Fe-S protein POLD1, without affecting the aggregation of lipoylated proteins. Mechanistic study revealed that NMN increased the expression of sirt2 and cellular reduced nicotinamide adenine dinucleotide phosphate (NADPH) level. Overexpression of sirt2 and sirt4 did not change the aggregation of lipoylated proteins, however, sirt2, but not sirt4, increased cellular NADPH levels and partially rescued cuproptosis. Inhibition of NAD+ kinase (NADK), which is responsible for generating NADPH, abolished the rescuing function of NMN and sirt2 for Es/Cu induced cell death. Taken together, our results suggested that DNA damage is a characteristic feature of cuproptosis. NMN can partially rescue cuproptosis by upregulating sirt2, increase intracellular NADPH content and maintain the level of Fe-S proteins, independent of the lipoamidase activity of sirt2.

Abstract Background Recognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses. Methods A prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome. Results This study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p

The thermal denaturation of rice structure and its starch crystalline/amorphous structure was studied by mid-infrared (MIR) spectroscopy and two-dimensional mid-infrared (2D-MIR) spectroscopy. The results indicated that the infrared absorption modes of rice starch included νOH-rice, νasCH2-rice, νsCH2-rice, νamide-Ⅰ-rice, νamide-Ⅱ-rice and νC-O-rice. As the measurement temperature increased (303-393 K), the sensitivity of rice starch crystals/amorphous structures to heat and the order of change were different from those in different origins. Further research on the relevant mechanism shows that there are some differences in heat resistance of different rice starch crystal/amorphous structure, which further affects its taste. The study expanded the scope of research on the thermal denaturation of rice structure and its starch crystals/amorphous structures using MIR spectroscopy and 2D-MIR spectroscopy.

Abstract Background Doxorubicin (Dox) is an effective chemotherapeutic drug for various cancers, but its clinical application is limited by severe cardiotoxicity. Dox treatment can transcriptionally activate multiple cardiotoxicity-associated genes in cardiomyocytes, the mechanisms underlying this global gene activation remain poorly understood. Methods and results Herein, we integrated data from animal models, CUT&Tag and RNA-seq after Dox treatment, and discovered that the level of H3K27ac (a histone modification associated with gene activation) significantly increased in cardiomyocytes following Dox treatment. C646, an inhibitor of histone acetyltransferase, reversed Dox-induced H3K27ac accumulation in cardiomyocytes, which subsequently prevented the increase of Dox-induced DNA damage and apoptosis. Furthermore, C646 alleviated cardiac dysfunction in Dox-treated mice by restoring ejection fraction and reversing fractional shortening percentages. Additionally, Dox treatment increased H3K27ac deposition at the promoters of multiple cardiotoxic genes including Bax, Fas and Bnip3, resulting in their up-regulation. Moreover, the deposition of H3K27ac at cardiotoxicity-related genes exhibited a broad feature across the genome. Based on the deposition of H3K27ac and mRNA expression levels, several potential genes that might contribute to Dox-induced cardiotoxicity were predicted. Finally, the up-regulation of H3K27ac-regulated cardiotoxic genes upon Dox treatment is conservative across species. Conclusions Taken together, Dox-induced epigenetic modification, specifically H3K27ac, acts as a molecular switch for the activation of robust cardiotoxicity-related genes, leading to cardiomyocyte death and cardiac dysfunction. These findings provide new insights into the relationship between Dox-induced cardiotoxicity and epigenetic regulation, and identify H3K27ac as a potential target for the prevention and treatment of Dox-induced cardiotoxicity.

Abstract Neuropilin-1 (NRP1), a co-receptor for various cytokines, including TGF-β, has been identified as a potential therapeutic target for fibrosis. However, its role and mechanism in renal fibrosis remains elusive. Here, we show that NRP1 is upregulated in distal tubular (DT) cells of patients with transplant renal insufficiency and mice with renal ischemia-reperfusion (I-R) injury. Knockout of Nrp1 reduces multiple endpoints of renal injury and fibrosis. We find that Nrp1 facilitates the binding of TNF-α to its receptor in DT cells after renal injury. This signaling results in a downregulation of lysine crotonylation of the metabolic enzyme Cox4i1, decreases cellular energetics and exacerbation of renal injury. Furthermore, by single-cell RNA-sequencing we find that Nrp1-positive DT cells secrete collagen and communicate with myofibroblasts, exacerbating acute kidney injury (AKI)-induced renal fibrosis by activating Smad3. Dual genetic deletion of Nrp1 and Tgfbr1 in DT cells better improves renal injury and fibrosis than either single knockout. Together, these results reveal that targeting of NRP1 represents a promising strategy for the treatment of AKI and subsequent chronic kidney disease.

Abstract Species conservation assessments using the criteria outlined by the International Union for the Conservation of Nature Red List can be compromised by limited data availability. Species-rich tropical plant taxa with numerous microendemics are particularly problematic. This study focusses on the Begonia flora of the Indonesian island of Sulawesi, comprised of 65 herbaceous species mainly found in rainforest habitats. Sixty-two species are Sulawesi endemics, including 20 species restricted to limestone karst landscapes. Forty-eight species are represented by fewer than 10 herbarium collections. Here, we outline and discuss an approach that, despite these data limitations, allows meaningful conservation assessments by integrating analyses of occurrences, data primarily based on remote sensing approaches, including forest landscape integrity, forest cover loss, and land cover, and extent of suitable habitat estimation. The results indicate that most Sulawesi Begonia species are narrow endemics whose rainforest habitats have substantially deteriorated in the last two decades: 27 species are assessed as Critically Endangered, 24 as Endangered, six as Vulnerable, five as Least Concern, and three species are Data Deficient. Conservation action, including extension of the protected area network in Sulawesi with emphasis on areas of old-growth forest and limestone karst landscapes, and strengthening of ex-situ living collections, is recommended.

Abstract Background The inhalational anesthetic isoflurane is commonly utilized in clinical practice, particularly in the field of pediatric anesthesia. Research has demonstrated its capacity to induce neuroinflammation and long-term behavioral disorders; however, the underlying mechanism remains unclear [1]. The cation-chloride cotransporters Na+–K+–2Cl−–1 (NKCC1) and K+–2Cl−–2 (KCC2) play a pivotal role in regulating neuronal responses to gamma-aminobutyric acid (GABA) [2]. Imbalances in NKCC1/KCC2 can disrupt GABA neurotransmission, potentially leading to neural circuit hyperexcitability and reduced inhibition following neonatal exposure to anesthesia [3]. Therefore, this study postulates that anesthetics have the potential to dysregulate NKCC1 and/or KCC2 during brain development. Methods We administered 1.5% isoflurane anesthesia to neonatal rats for a duration of 4 h at postnatal day 7 (PND7). Anxiety levels were assessed using the open field test at PND28, while cognitive function was evaluated using the Morris water maze test between PND31 and PND34. Protein levels of NKCC1, KCC2, BDNF, and phosphorylated ERK (P-ERK) in the hippocampus were measured through Western blotting analysis. Pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were quantified using ELISA. Results We observed a decrease in locomotion trajectories within the central region and a significantly shorter total distance in the ISO group compared to CON pups, indicating that isoflurane induces anxiety-like behavior. In the Morris water maze (MWM) test, rats exposed to isoflurane exhibited prolonged escape latency onto the platform. Additionally, isoflurane administration resulted in reduced time spent crossing in the MWM experiment at PND34, suggesting long-term impairment of memory function. Furthermore, we found that isoflurane triggered activation of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; downregulated KCC2/BDNF/P-ERK expression; and increased the NKCC1/KCC2 ratio in the hippocampus of PND7 rats. Bumetadine (NKCC1 specific inhibitors) reversed cognitive damage and effective disorder induced by isoflurane in neonatal rats by inhibiting TNF-α activation, normalizing IL-6 and IL-1β levels, restoring KCC2 expression levels as well as BDNF and ERK signaling pathways. Based on these findings, it can be speculated that BDNF, P-ERK, IL-1β, IL-6 and TNF - α may act downstream of the NKCC1/KCC2 pathway. Conclusions Our findings provide evidence that isoflurane administration in neonatal rats leads to persistent cognitive deficits through dysregulation of the Cation-Chloride Cotransporters NKCC1 and KCC2, BDNF, p-ERK proteins, as well as neuroinflammatory processes.

Abstract The purpose of this study was to investigate the relationship between circulating cytokines and liver function and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with radiotherapy combined with tislelizumab and anlotinib. The liver function indexes and pre-treatment levels of cytokines in 47 patients were measured by chemical method and flow cytometry. The median follow-up was 23.1 months. The objective response and the disease control rates were 46.8% and 68.1%, while overall survival (OS) and progression-free survival (PFS) were 12.6 and 11.4 months, respectively. Adverse events (2.1%) were grade 3–4. In addition to stage, intrahepatic metastasis and Child–Pugh score, pre-treatment interleukin-6 (IL-6) was the main cytokine affecting OS and PFS (p

Purpose: Autistic symptom improvement can be observed in children treated with acupuncture, but the mechanism is still being explored. In the present study, we used scalp acupuncture to treat autism rat model, and then their improvement in the abnormal behaviors and specific mechanisms behind were revealed by detecting animal behaviors, analyzing the RNA sequencing of the prefrontal cortex (PFC), and observing the ultrastructure of PFC neurons under the transmission electron microscope. Methods: On gestational day 12.5, Wistar rats were given valproic acid (VPA) by intraperitoneal injection, and their offspring were considered to be reliable rat models of autism. They were randomized to VPA or VPA-acupuncture group (n = 8). Offspring of Wistar pregnant rats that were simultaneously injected with saline were randomly selected as the wild-type group (WT). VPA_acupuncture group rats received acupuncture intervention at 23 days of age for 4 weeks, and the other two groups followed without intervention. After the intervention, all experimental rats underwent behavioral tests. Immediately afterward, they were euthanized by cervical dislocation, and their prefrontal cortex was isolated for RNA sequencing and transmission electron microscopy. Results: The main results are as follows: 1. Animal behavioural tests: VPA group rats showed more anxiety-like behaviour and repetitive, stereotyped behaviour than WT group rats. While VPA group rats showed less spatial exploration ability, activity level, social interaction, and social novelty preference than WT group rats. It was gratifying to observe that acupuncture indeed improved these abnormal behaviors of autism rat model. 2. RNA-sequencing: The three groups of rats differed in the expression and enrichment pathways of multiple genes related to synaptic function, neural signal transduction, immune-inflammatory responses and circadian rhythm regulation. Our experiments indicated that acupuncture can alleviate the major symptoms of ASD by improving these neurological abnormalities. 3. Under the transmission electron microscopy, several lysosomes and mitochondrial structural abnormalities were observed in the prefrontal neurons of VPA group rats, which were manifested as atrophy of the mitochondrial membrane, blurring or disappearance of the mitochondrial cristae, and even vacuolization. Moreover, the number of synapses and synaptic vesicles was relatively small. Conversely, the mitochondrial structure of rats in the WT group and VPA_acupuncture was normal, and the number of synapses and synaptic vesicles was relatively large. Conclusion: Acupuncture effectively improved the abnormal behaviors of autism rat model and the ultrastructure of the PFC neurons, which might worked by improving their abnormal synaptic function, synaptic plasticity promoting neuronal signal transduction and regulating immune-inflammatory responses.

IntroductionPhysical inactivity and mental health disorders are emerging threats to public health in China. Previous research on links between exercise and mental wellbeing have focused on clinical populations, with little evidence from the general population, particularly younger adults. We aimed to investigate associations between physical fitness and mental health in Chinese college students.MethodsIn this series, of cross-sectional observational studies, we enrolled 7,468 Chinese college students aged 16–24 years in 199 classes at Changzhou Vocational Institute of Engineering between Sept 1, 2017, and Jun 30, 2018. Exposures of interest were the students’ physical fitness level, measured by the Chinese University Students Physique Test. The primary outcomes were mental health situations, measured by the University Personality Inventory (UPI). The multivariable linear regression models were used to assess the relationship between the levels of physical fitness and mental disorders symptoms.ResultsCompleted mental health and physical fitness data were available for 6,724 participants aged 16–24 years. Compared with the failed group, the corresponding levels of difference in overall UPI scores were − 1.45 scores (95% CI: −2.45, −0.46; p

The shift of agricultural labor force to non-agricultural sectors has paralleled China's economic development, leading to a substantial rise in labor costs relative to capital. Consequently, the agricultural production has witnessed a shift towards capital-intensive practices. The capital deepening coincides with the significant increase in China's grain output while the main cause of capital deepening in China's grain production is poorly understood. This study examines the effect of increasing in various capital investments on the grain yield growth and growth convergence in China's main production areas, based on the data collected from the data set of the Compilation of Cost-Benefit Data of Agricultural Products (CCBDAP). Results show that the increases of chemical fertilizer, pesticide and machinery input have played key roles in the increase of grain yield. For early indica rice, japonica rice, wheat and maize, the average land output bears a β convergence. These findings suggest that more capital investments are supposed to accelerate the growth of grain yield per unit of land, take the opportunity of practicing the cross-provincial balance system of occupation and compensation of cultivated land. Moreover, strategic adjustments to the spatial distribution of grain cultivation are recommended to maximize the utilization of limited arable land resources while upholding national food security objectives.

The seamless asphalt plug expansion joint integrates a traditional asphalt plug joint (APJ) with an overlying continuous asphalt concrete layer, preventing block failure of the asphalt plug joint and enhancing driving comfort. However, typical damages such as fatigue cracking, rutting, and permanent deformation often occur in the upper asphalt layer. This is attributed to the inadequate stiffness of the lower joint plug mastic, particularly under high temperatures and heavy loads. To extend the service life of asphalt plug expansion joints under such conditions and enhance their durability, efforts were made to bolster the performance of the lower asphalt plug joint mixture and improve anti-rutting performance. This study involved: (1) Qualifying APJ mixture requirements under high temperature and heavy load by focusing on two critical material properties: good rutting resistance and permanent deformation resistance. High temperature rheological properties of these binders were examined through temperature scanning tests and multi-stress creep recovery tests (MSCR). (2) Exploring the impact of binder-aggregate ratios and specimen molding methods (standard compaction, paving vibration and pre-mixing) on the bonding strength and rutting resistance of the APJ mixture. This analysis was conducted using pull-off tests and dynamic stability tests. (3) Development of a novel APJ featuring dowel bars to enhance vertical deflection resistance and joint horizontal movement. Comprehensive laboratory tests showcased the modified joint structure's resilience after numerous test cycles, demonstrating exceptional resistance to bending and vertical deformation. The significant findings from this research provide valuable insights for optimal material selection, appropriate joint design, and installation guidelines for seamless asphalt plug expansion joints.

Objective·To investigate the effects of trimethylamine oxide (TMAO) on cardiac function in mice with hypertrophic cardiomyopathy (HCM) and its potential molecular mechanism.Methods·Mice with myosin heavy chain 6 (Myh6) c.1211G>A (p.R404Q+/-) point mutation were used as the animal model. According to dietary supplementation of TMAO and TMAO inhibitor iodomethylcholine (IMC), the wild type (WT) mice and HCM mice were divided into WT group, HCM group (HCM-1 group, HCM-2 group), WT+TMAO group, HCM+TMAO group and HCM+IMC group, respectively. Left ventricular fraction shortening (FS) and left ventricular posterior wall thickness (LVPW) were assessed by echocardiography in all mice. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum TMAO concentration of mice in the HCM-1 group and WT group. The regularity of myocardial cell arrangement of mice was evaluated by hematoxylin and eosin staining (HE staining). The proportion of myocardial fibrosis was evaluated by Masson staining. The activity of protein kinase A (PKA) in mouse myocardial tissue was detected by PKA kit. The expression of ryanodine receptor 2 (RyR2) and p-RyR2(S2808) in mouse myocardial tissue was detected by Western blotting.Results·The results of echocardiography showed that at 12 months of age, the FS of mice in the WT+TMAO group and HCM+TMAO group were lower than those in the corresponding WT group and HCM-1 group, respectively (P

Retinitis pigmentosa (RP) is the most common type of inherited retinal dystrophy. The course of RP is irreversible and leads to progressive loss of vision. It is characterized by hypotrophic degeneration of photoreceptor cells and retinal pigment epithelium. Multiple factors are involved in the development of the disease, including apoptosis, oxidative stress, and inflammatory/immune responses. In the past decades, gene therapy, stem cell therapy and other therapeutic approaches have been extensively investigated. However, due to the heritability and high heterogeneity of the disease and the difficulty in diagnosis and treatment, there is still a lack of standardized and effective therapies. Therefore, there is a need to develop new diagnostic and therapeutic approaches suitable for diseases with pathogenic mutations. With the understanding of the interaction between gene expression regulation and retinal pathology, the value of clinical applications of non-coding RNAs (ncRNAs) in retinal degeneration has gained attention. There is growing evidence that ncRNAs are widely distributed and involved in the regulation of multiple biological processes in the retina as well as processes associated with the development of RP, making them promising biomarkers for the diagnosis, treatment, and prognosis of RP. This paper reviews the crosstalk between ncRNA and RP, systematically discusses the role of ncRNAs in normal retinal cell physiology and RP pathogenesis and explores the potential of ncRNAs as therapeutic agents for clinical applications in RP.

Abstract Lung adenocarcinoma (LUAD) remains one of the most aggressive tumors and the efficacy of conventional treatment has been bleak. Nowadays, gene-targeted therapy has become a new favorite in tumor therapy. Herein, we investigated the effect of platelet derived growth factor BB (PDGFBB) on LUAD. Firstly, PDGFBB was upregulated in LUAD patients and closely linked with poor survival. Furthermore, the expression of PDGFBB and PDGFRα/β in LUAD cells was higher than that in normal lung cells. By loss-of-function with herpes simplex virus (HSV)-PDGFi-shRNA, we found that PDGFBB knockdown caused a significant decrease in proliferation and migration, but evoked apoptosis of LUAD cells in vitro. Conversely, exogenous PDGFBB held adverse effect. Additionally, A549 cells with PDGFBB knockdown had a low probability of tumorigenesis in vivo. Moreover, PDGFBB knockdown restrained the growth of xenografts derived from normal A549 cells. Mechanistically, PDGFBB knockdown suppressed PI3K/AKT and Ras/MAPK signaling, while PDGFBB was the opposite. Therefore, we concluded that PDGFBB might facilitate the tumorigenesis and malignancy of LUAD through its functional downstream nodes—PI3K/AKT and Ras/MAPK signaling, which supported that PDGFBB could serve as a rational therapeutic target for LUAD.

Abstract Dynamic network link prediction is extensively applicable in various scenarios, and it has progressively emerged as a focal point in data mining research. The comprehensive and accurate extraction of node information, as well as a deeper understanding of the temporal evolution pattern, are particularly crucial in the investigation of link prediction in dynamic networks. To address this issue, this paper introduces a node representation learning framework based on Graph Convolutional Networks (GCN), referred to as GCN_MA. This framework effectively combines GCN, Recurrent Neural Networks (RNN), and multi-head attention to achieve comprehensive and accurate representations of node embedding vectors. It aggregates network structural features and node features through GCN and incorporates an RNN with multi-head attention mechanisms to capture the temporal evolution patterns of dynamic networks from both global and local perspectives. Additionally, a node representation algorithm based on the node aggregation effect (NRNAE) is proposed, which synthesizes information including node aggregation and temporal evolution to comprehensively represent the structural characteristics of the network. The effectiveness of the proposed method for link prediction is validated through experiments conducted on six distinct datasets. The experimental outcomes demonstrate that the proposed approach yields satisfactory results in comparison to state-of-the-art baseline methods.

Abstract Kikuchi‐Fujimoto Disease (KFD), also known as Kikuchi disease or Kikuchi histiocytic necrotizing lymphadenitis, is a rare and self‐limiting condition characterized by cervical lymphadenopathy and fever, primarily affecting young Asian adults. The aetiology of KFD remains unknown, although various infectious agents have been suggested as potential triggers. With the emergence of the COVID‐19 pandemic, cases of post‐COVID‐19 KFD and post‐COVID‐19 vaccine KFD have been reported. In this article, we present the first case of post‐COVID‐19 KFD in Hong Kong. A 24‐year‐old man developed fever and painful neck swelling 1 month after recovering from COVID‐19. Diagnostic evaluation, including ultrasound‐guided fine needle aspiration cytology (FNAC), confirmed the diagnosis of KFD. The patient's symptoms resolved spontaneously with supportive care. This case underscores the importance of considering KFD as a potential differential diagnosis in patients presenting with cervical lymphadenopathy and fever following COVID‐19 recovery or vaccination.

Diagnosis of intracranial tuberculoma remains a challenge due to its rarity, non-specific clinical presentation, and radiological findings. Herein, we describe a case of intracranial tuberculomas in a male diabetic patient who presented headache and vomiting on admission. Neuroimaging findings indicated multiple ring contrast-enhanced lesions with extensive perilesional edema. However, a cerebrospinal fluid (CSF) examination was normal. When a biopsy of brain lesions was performed, pathological characteristics of tuberculosis were absent and acid-fast staining was negative. A tuberculosis diagnosis was subsequently obtained from an Xpert MTB/RIF Ultra assay of formalin-fixed paraffin-embedded brain tissue. The patient was treated with an optimized anti-tuberculosis regimen which included high-dose intravenous administration of rifampicin and isoniazid, and oral administration of linezolid. The patient recovered well and exhibited marked clinical improvement. This case report demonstrates that when CSF analysis does not indicate the presence of intracranial tuberculomas, analysis of formalin-fixed paraffin-embedded brain tissue specimens with the Xpert MTB/RIF Ultra assay may be able to confirm a diagnosis. Furthermore, a high dose of rifampicin and isoniazid plus linezolid may improve patient outcome.

PurposeThe prevalence of comorbid pain and Bipolar Disorder in clinical practice continues to be high, with an increasing number of related publications. However, no study has used bibliometric methods to analyze the research progress and knowledge structure in this field. Our research is dedicated to systematically exploring the global trends and focal points in scientific research on pain comorbidity with bipolar disorder from 2003 to 2023, with the goal of contributing to the field.MethodsRelevant publications in this field were retrieved from the Web of Science core collection database (WOSSCC). And we used VOSviewer, CiteSpace, and the R package “Bibliometrix” for bibliometric analysis.ResultsA total of 485 publications (including 360 articles and 125 reviews) from 66 countries, 1019 institutions, were included in this study. Univ Toront and Kings Coll London are the leading research institutions in this field. J Affect Disorders contributed the largest number of articles, and is the most co-cited journal. Of the 2,537 scholars who participated in the study, Stubbs B, Vancampfort D, and Abdin E had the largest number of articles. Stubbs B is the most co-cited author. “chronic pain,” “neuropathic pain,” “psychological pain” are the keywords in the research.ConclusionThis is the first bibliometric analysis of pain-related bipolar disorder. There is growing interest in the area of pain and comorbid bipolar disorder. Focusing on different types of pain in bipolar disorder and emphasizing pain management in bipolar disorder are research hotspots and future trends. The study of pain related bipolar disorder still has significant potential for development, and we look forward to more high-quality research in the future.

Abstract In this research, a 3D brain organoid model is developed to study POLG‐related encephalopathy, a mitochondrial disease stemming from POLG mutations. Induced pluripotent stem cells (iPSCs) derived from patients with these mutations is utilized to generate cortical organoids, which exhibited typical features of the diseases with POLG mutations, such as altered morphology, neuronal loss, and mitochondiral DNA (mtDNA) depletion. Significant dysregulation is also identified in pathways crucial for neuronal development and function, alongside upregulated NOTCH and JAK‐STAT signaling pathways. Metformin treatment ameliorated many of these abnormalities, except for the persistent affliction of inhibitory dopamine‐glutamate (DA GLU) neurons. This novel model effectively mirrors both the molecular and pathological attributes of diseases with POLG mutations, providing a valuable tool for mechanistic understanding and therapeutic screening for POLG‐related disorders and other conditions characterized by compromised neuronal mtDNA maintenance and complex I deficiency.

IntroductionInternet use is changing nutritional intake and health outcomes, but the results are mixed, and less attention is given to the rural developing regions. Based on the China Health and Nutrition Survey (CHNS) data from 2004 to 2015, this study seeks to better understand the effect of Internet use on nutritional intake and health outcomes.MethodsAn instrumental variable estimation is used to address endogeneity problem.ResultsThe results show that Internet use improves the dietary knowledge of rural residents, and thus has a positive impact on dietary quality, such as healthy eating index (HEI) and dietary diversity score (DDS). The higher the dietary quality, the better the nutritional health status. However, results also show that Internet use increases the risk of overweight, and obesity among rural Chinese residents. Because Internet use has significantly reduced the physical activity of rural residents in China. Interestingly, we also find that the Internet increases the risk of chronic diseases such as diabetes and high blood pressure, but there is a positive causal relationship between Internet use and the self-assessment score of health.DiscussionOur findings suggest that there may be a serious lack of awareness of the health risks of chronic diseases among Chinese rural residents. Therefore, policymakers are suggested to consider the possible negative effects when promoting digital development.

The Cloud-based Liquid Pipeline Simulator(CloudLPS) is a universal liquid pipeline simulation software with completely independent intellectual property rights in China. Herein, its applications are introduced. Its operation processes from pipeline network modeling and simulation calculation to result viewing are elaborated based on a specific case. Then, calculations are performed with CloudLPS for various operating conditions, including steady-state transportation, transient water hammer, and alternating transportation of cold and hot oil, after which the results are compared with those obtained from the foreign commercial software SPS and TLNET, making the discovery that the CloudLPS has comparable accuracy in terms of hydrodynamic and thermal simulations. Subsequently, CloudLPS is applied to solve practical pipeline problems such as normal-temperature transportation, heated transportation, and alternating transportation of cold and hot oil. By comparing the results of these practical applications with the field data, it is proven that the CloudLPS can meet the requirements of the actual engineering calculations. Finally, the two special features of CloudLPS, including visual control logic construction and energy consumption optimization, are presented. The results of this paper indicate that CloudLPS is of great competence in hydrodynamic and thermal simulations, logic control, and energy consumption optimization.

Objective To investigate the detection and clinical application studies based on malaria protein VAR2CSA(VAR2) synthetic peptide specifically binding to circulating tumor cells (CTCs). Methods The peptide sequence of the functional structural domain of malaria protein VAR2CSA was selected to synthesize VAR2 that enriched CTCs based on nano-microfluidic technology, and used VAR2 synthetic peptide to detect enriched cells to establish a novel detection protocol for CTCs. Cellular immuno-fluorescence staining, flow cytometry and tumor cell doping recovery assays were used to analyze the specific binding and recovery efficiency of VAR2 synthetic peptide with tumor cells of different tissue sources and compare with immuno-staining-fluorescence in situ hybridization (imFISH) assay. Twenty-two colorectal cancer patients and twenty-two healthy individuals were selected, and the VAR2 synthetic peptide was used to detect peripheral blood CTCs in both. The VAR2 synthetic peptide was used to compare the positive detection rate of CTCs in patients with different TNM stages. Results The VAR2 synthetic peptide bound specifically to tumor cells collected from different tissue sources of human colon cancer cell line SW620, human breast cancer cell line MCF7 and human esophageal squamous carcinoma cell line KYSE180.The VAR2 synthetic peptide detected 100 SW620, MCF7 and KYSE180 tumor cells mixed into 3 mL of peripheral blood with recovery rates of 82.8%±8.41%, 56.2%±3.57%, 86.6%±8.19%, which were not significantly different from the imFISH assay. The VAR2 synthetic peptide assay recoveries of 50, 100, and 200 SW620 tumor cells were 80.7%, 82.8%, and 84.7%, respectively, which did not correlate significantly with the number of adulterated tumor cells. The VAR2 synthetic peptide detected 63.6% positive CTCs in peripheral blood samples from patients with clinical colorectal cancer, which was higher than the 0.0% positive CTCs rate in the group of healthy subjects, and also correlated with depth of invasion, lymph node metastasis, distant metastasis, and clinical stage (P＜0.05). Conclusions The VAR2-based synthetic peptide may be applied in specific and non-antibody dependent CTCs detection in different tissue samples and so has good clinical application value for clinical staging and severity evaluation of tumor patients.

Abstract Advanced persistent threat (APT) attacks are malicious and targeted forms of cyberattacks that pose significant challenges to the information security of governments and enterprises. Traditional detection methods struggle to extract long-term relationships within these attacks effectively. This paper proposes an APT attack detection model based on graph convolutional neural networks (GCNs) to address this issue. The aim is to detect known attacks based on vulnerabilities and attack contexts. We extract organization-vulnerability relationships from publicly available APT threat intelligence, along with the names and relationships of software security entities from CVE, CWE, and CAPEC, to generate triple data and construct a knowledge graph of APT attack behaviors. This knowledge graph is transformed into a homogeneous graph, and GCNs are employed to process graph features, enabling effective APT attack detection. We evaluate the proposed method on the dataset constructed in this paper. The results show that the detection accuracy of the GCN method reaches 95.9%, improving by approximately 2.1% compared to the GraphSage method. This approach proves to be effective in real-world APT attack detection scenarios.

The location and size of tumors, treatment methods and prognosis of patients with head and neck cancer can seriously affect their oral function and neck activity, thereby affecting daily activities such as eating, speech and upper limb movement. Early rehabilitation after head and neck cancer surgery can accelerate functional recovery, alleviate discomfort symptoms, improve quality of life, and reduce unnecessary rehabilitation or treatment measures. Developing a clinical rehabilitation nursing pathway for head and neck cancer, forming personalized rehabilitation plans, and conducting early and effective nursing interventions are currently one of the key points of clinical work for patients with head and neck cancer. At present, domestic and foreign guidelines or consensus pays less attention to the impairments of speech function, chewing and swallowing function, neck and shoulder function etc., and lacks a systematic and comprehensive rehabilitation nursing guide or consensus to provide practical guidance for the care of patients with head and neck cancer. Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine organized relevant experts from Beijing, Shanghai, Sichuan, Shaanxi, Zhejiang and Anhui to draft Expert consensus on postoperative rehabilitation nursing of patients with head and neck cancer basing on previous literature and clinical nursing skills and experiences, of which the aim is to provide guidance for those patients in the aspects of oral care, nutritional support, flap donor area care, care after tracheotomy, chewing and swallowing rehabilitation, speech function rehabilitation, neck and shoulder function rehabilitation, restricted mouth opening rehabilitation, risk identification and prevention and follow-up.

When using open core tube sampling to measure the gas content in deep hole coal seams, the coal sample has a long exposure time. It is prone to pollution, and the gas loss is difficult to measure, resulting in large measurement errors. However, most of the existing sealed pressure maintaining sampling requires secondary expansion and complex structure. The sampling success rate is low, making it difficult to promote and apply on a large scale. In order to solve the above problems, a sealed pressure maintaining sampling device for deep holes in coal mines has been developed. The device adopts an overall structural design of 'two-stage piston+double-layer casing+coal sample cylinder'. By controlling the injection flow rate and injection time of the underground high-pressure water pump into the device, the ball valve switches from being sealed before sampling to being opened during sampling, and then to being sealed after sampling. The goal of sealing the coal sample in the coal sample cylinder is achieved, preventing contamination of the coal sample and gas escape during the sampling process. Four sets of coal samples from the same borehole and depth are collected using the conventional sampling method of an open core tube and a deep hole sealed pressure maintaining sampling device for comparative analysis of gas content. The on-site test results show that the sampling depth of the deep hole sealed pressure maintaining sampling device is close to 350 meters. Compared to conventional sampling methods, the gas content measured by deep hole sealed pressure maintaining sampling is 5.4% to 37%. The degree of deviation increases with the increase of sampling drilling depth. It indicates that the sealed pressure maintaining sampling device can improve the accuracy of deep hole coal seam gas content testing.

BackgroundThe protective efficacy of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination against the new-onset gastrointestinal (GI) symptoms following COVID-19 infection is critical among patients with inflammatory bowel disease (IBD); however, the optimal protective vaccine dose remains unknown. Therefore, this study aimed to clarify whether there is a correlation between SARS-CoV-2 vaccinations and GI symptoms following Omicron infection in patients with IBD.MethodsWe conducted a multicenter cross-sectional study of IBD patients among three tertiary hospitals in eastern China. Professional physicians collected all data using online questionnaires. The patients were stratified into four groups: patients who were unvaccinated and patients who received one, two, or three vaccination doses. The primary outcome was the presence of any new-onset GI symptoms after SARS-CoV-2 infection before a negative SARS-CoV-2 nucleic acid test or a negative self-testing for antigens.ResultsIn total, 536 patients with IBD (175 unvaccinated, 31 vaccinated, 166 vaccinated with two doses, and 164 vaccinated with three doses) reported having COVID-19 infection. Compared with the unvaccinated, the three vaccination doses group was associated with reduced GI symptoms after infection (adjusted odds ratio = 0.56, 95% confidence interval 0.34–0.90, P < 0.05). Reduced diarrhea (adjusted odds ratio = 0.54, 95% confidence interval 0.31–0.92, P < 0.05) and nausea or vomiting (adjusted odds ratio = 0.45, 95% confidence interval 0.21–0.92, P < 0.05) were observed in the three vaccination doses group compared with the unvaccinated group.ConclusionsIn conclusion, in the 536 patients with IBD who reported COVID-19 infection, we found that the three vaccination doses, but not the one or two doses group, were associated with reduced GI symptoms after infection compared with the unvaccinated group.

Background: Previous studies have shown that the nicotinamide adenine dinucleotide (NAD+) precursors, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), protect against endogenously or exogenously induced DNA damage. However, whether the two compounds have the same or different efficacy against DNA damage is not clear. In the current study, we systematically compared the effects of NMN and NR on cisplatin-induced DNA damage in HeLa cells. Methods: To evaluate the protective effects of NMN or NR, HeLa cells were pretreated with different doses of NMN or NR followed with 10 μM of cisplatin treatment. Cell viability was examined by Trypan blue staining assay. For observing the DNA damage repair process, HeLa cells were treated with 10 μM of cisplatin for 12 h, followed with 10 mM NMN or NR treatment for another 8, 16, 24, or 32 h, DNA damage levels were assessed for each time point by immunofluorescent staining against phosphor-H2AX (γH2AX) and alkaline comet assay. The effects of NMN and NR on intracellular NAD+ and reactive oxygen species (ROS) levels were also determined. Results: NMN and NR treatment alone did not have any significant effects on cell viability, however, both can protect HeLa cells from cisplatin-induced decrease of cell viability with similar efficacy in a dose-dependent manner. On the other hand, while both can reduce the DNA damage levels in cisplatin-treated cells, NR exhibited better protective effect. However, both appeared to boost the DNA damage repair process with similar efficacy. NMN or NR treatment alone could increase cellular NAD+ levels, and both can reverse cisplatin-induced decrease of NAD+ levels. Finally, while neither NMN nor NR affected cellular ROS levels, both inhibited cisplatin-induced increase of ROS with no significant difference between them. Conclusion: NR have a better protective effect against cisplatin-induced DNA damage than NMN.

Mangroves are an essential component of coastal ecosystems. Accurate and effective identification and extraction of mangrove areas from remote sensing imagery is crucial for monitoring changes in the nearshore ecological environment. High-resolution remote sensing imagery is often difficult or expensive to obtain and usually lacks sufficient temporal coverage, so most monitoring of mangrove forests still relies on medium- or low-resolution imagery, resulting in inaccurate distribution of extracted mangrove areas. The super-resolution (SR) images generated by increasingly widely used deep learning (DL) models may be an alternative. To validate this, we evaluated the extraction of mangroves from SR images generated by four DL models (i.e., enhanced super-resolution generative adversarial networks (ESRGAN), Real-ESRGAN, vast-receptive-field pixel attention network (VapSR), and image restoration methods using swin transformer (SwinIR)). The models were trained on paired (high-resolution) Chinese GF-1 satellite images and (low-resolution) Landsat 8 datasets. The performance of model fitting, vegetation indices, and extracted mangrove areas was evaluated using three commonly used classifiers (i.e., support vector machines (SVM), random forest (RF), and gradient-boosted decision tree (GBDT)) in combination with ground-truth sampling points and public mangrove datasets. Results showed that: (1) the SR images generated by DL-based models can facilitate the extraction of mangrove features. (2) The quality evaluation metrics peak signal-to-noise ratio (PSNR) and structural similarity index measurements (SSIM) cannot be regarded as absolute criteria for SR images, especially when the SR images were used for mangrove feature extractions. (3) The SR image generated by the VapSR model was best suited for extracting mangrove forests and performed even better than the original high-resolution images. (4) Taking a public dataset as a benchmark, the mangrove areas extracted from the SR image generated by the VapSR model were closer to the benchmark than the original Landsat-8 and GF-1. Overall, the DL-based SR models can enhance mangrove extractions and potentially have widespread applications.

The hypothesis of paternal origins of health and disease (POHaD) indicates that paternal exposure to adverse environment could alter the epigenetic modification in germ line, increasing the disease susceptibility in offspring or even in subsequent generations. p,p′-Dichlorodiphenyldichloroethylene (p,p′-DDE) is an anti-androgenic chemical and male reproductive toxicant. Gestational p,p′-DDE exposure could impair reproductive development and fertility in male offspring. However, the effect of paternal p,p′-DDE exposure on fertility in male offspring remains uncovered. From postnatal day (PND) 35 to 119, male rats (F0) were given 10 mg/body weight (b.w.) p,p′-DDE or corn oil by gavage. Male rats were then mated with the control females to generate male offspring. On PND35, the male offspring were divided into 4 groups according whether to be given the high-fat diet (HF): corn oil treatment with control diet (C-C), p,p′-DDE treatment with control diet (DDE-C), corn oil treatment with high-fat diet (C-HF) or p,p′-DDE treatment with high-fat diet (DDE-HF) for 35 days. Our results indicated that paternal p,p′-DDE exposure did not affect the male fertility of male offspring directly, but decreased sperm quality and induced testicular apoptosis after the high-fat diet treatment. Further analysis demonstrated that paternal exposure to p,p′-DDE and pre-pubertal high-fat diet decreased sperm Igf2 DMR2 methylation and gene expression in male offspring. Hence, paternal exposure to p,p′-DDE and pre-pubertal high-fat diet increases the susceptibility to male fertility impairment and sperm Igf2 DMR2 hypo-methylation in male offspring, posing a significant implication in the disease etiology.

Objective After transradial angiography, based on the non-invasive blood pressure of the patient's healthy upper limb after surgery, the adjustmenf of the pressure value of the radial artery hemostat airbag can achieve both hemostasis and reduce the occurrence of finger swelling on the puncture side, improve the patient's comfort. Methods A total of 274 postoperative patients received coronary angiography at Nanjing Jiangbei Hospital from February to November 2022 were selected and randomly divided into control group and observation group (n=137, each). The control group was adjusted by instructions of the radial artery hemostat, while the observation group adjusted the hemostatic pressure of the radial artery hemostat balloon based on the non-invasive arterial blood pressure value of the patient's healthy upper limb. The situation of hand swelling, bleeding, and patient pain scores in both groups of affected limbs were observed. Results The degree of swelling, bleeding, and pain in the affected limbs and hands of the observation group was better than those of the control group (P＜0.05). Conclusion After transradial angiography, adjusting the hemostatic pressure value of the radial artery hemostatic balloon according to the non-invasive arterial blood pressure value of the patient's healthy upper limb at different time periods can reduce the degree of hand swelling, bleeding and pain in the affected limb.

Baicalin has been shown to promote spatial learning and neural regeneration, which might increase the differentiation of neural stem cells in Alzheimer’s disease (AD) rat models. We aimed to study the role of baicalin on neuronal pentraxin-1 (NPTX-1), neuronal pentraxin-2 (NPTX-2), and C-reactive protein (CRP) in AD model rats.

Abstract Background Diabetic retinopathy is a leading cause of preventable blindness in Canada. Clinical guidelines recommend annual diabetic retinopathy screening for people living with diabetes to reduce the risk and progression of vision loss. However, many Canadians with diabetes do not attend screening. Screening rates are even lower in immigrants to Canada including people from China, Africa, and the Caribbean, and these groups are also at higher risk of developing diabetes complications. We aim to assess the feasibility, acceptability, and fidelity of a co-developed, linguistically and culturally tailored tele-retinopathy screening intervention for Mandarin-speaking immigrants from China and French-speaking immigrants from African-Caribbean countries living with diabetes in Ottawa, Canada, and identify how many from each population group attend screening during the pilot period. Methods We will work with our health system and patient partners to conduct a 6-month feasibility pilot of a tele-retinopathy screening intervention in a Community Health Centre in Ottawa. We anticipate recruiting 50–150 patients and 5–10 health care providers involved in delivering the intervention for the pilot. Acceptability will be assessed via a Theoretical Framework of Acceptability-informed survey with patients and health care providers. To assess feasibility, we will use a Theoretical Domains Framework-informed interview guide and to assess fidelity, and we will use a survey informed by the National Institutes of Health framework from the perspective of health care providers. We will also collect patient demographics (i.e., age, gender, ethnicity, health insurance status, and immigration information), screening outcomes (i.e., patients with retinopathy identified, patients requiring specialist care), patient costs, and other intervention-related variables such as preferred language. Survey data will be descriptively analyzed and qualitative data will undergo content analysis. Discussion This feasibility pilot study will capture how many people living with diabetes from each group attend the diabetic retinopathy screening, costs, and implementation processes for the tele-retinopathy screening intervention. The study will indicate the practicability and suitability of the intervention in increasing screening attendance in the target population groups. The study results will inform a patient-randomized trial, provide evidence to conduct an economic evaluation of the intervention, and optimize the community-based intervention.

Objective To investigate the endoscopic transoral ⁃ medial pterygomandibular fold approach anatomic procedures for jugular foramen, and to analyze the clinical feasibility of this approach. Methods and Results In the anatomical laboratory of the Surgical Treatment Technology Innovation Unit of Nasal Skull Base Tumor in Eye & ENT Hospital of Fudan University, a total of 5 specimens of necroheads (10 sides) were taken as research objects to simulate the anatomical steps of entering the jugular foramina and its adjacent structures through the oral pterygomandibular fold medial approach, and observe and describe important anatomical markers. 1) Anatomical procedures of the jugular foramen: firstly, the soft palate mucosa and suprapharyngeal retractive muscle were cut through the medial incision of pterygomandibular fold to enter anterior parapharyngeal space, the adipose tissue in the space was removed, and the stylopharyngeal fascia and stylopharyngeal muscle group were exposed. After the stylopharyngeal fascia was removed, the internal carotid artery (ICA) was further exposed and the jugular foramen was exposed. 2) The jugular foramen and its adjacent anatomical structures: the upper boundary of the jugular foramen was jugular bulbous fossa, the anterior was ICA, the anterolateral lateral was styloid process, the posterolateral boundary was the lateral rectus of head and transverse process of atlas, the medial boundary was the hypoglossal nerve and medial of occipital condyle, and the lateral boundary was the mastoid, digastric and facial nerves. Conclusions Endoscopic transoral⁃medial pterygomandibular fold approach for jugular foramen has better visual field, wider exposure range and shorter path.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by recurrent eczematous lesions with dry skin and refractory pruritus. The pathogenesis of AD is complex and one of the reasons may be related to the skin microbial environment. Multiple studies have found that bathing may be associated to skin barrier function and different bathing method may affect the severity of AD. This paper focuses on the bathing method of children with AD as well as the cleansers, and reviews relevant guidelines and evidence-based medicine.

Objective Collarless‐polished‐tapered (CPT) stems have been widely used in total hip replacement (THR). Given that various types of cups are combined with CPT in clinical practice, however, what cup type performs the best for use with CPT is still unclear. This study aimed to investigate the effects of three types of commonly used cups with CPT on revision and survival life using multi‐factor analysis. Methods This study is a cohort study using the data between October 1998 to September 2021. The data of THR patients with ZCA All‐poly Acetabular Cup, Continuum Acetabular System, and Trilogy Acetabular System with CPT were collected from several hospitals in the UK. The patients aged from 20 to 97 (n = 5981, 2345 male and 3636 female). Age, gender, body mass index, diagnosis, surgeon grade, cup material, cup size, surgical approach, survival life, complications, and Harris hip scores (HHS) were analyzed in relation to revision status. SPSS statistical software was used to analyze the relationship among various factors. The main statistical methods included chi‐square with cross tables, analysis of variance (ANOVA) and survival analysis. Results The results in relation to HHS shows that the continuum cup has the best outcome in the postoperative period of 1 and 5 years (1 year = 90.7, 5 years = 91.3; P

Stress relaxation cracking (SRC) is considered one of the major failure mechanisms for 347H stainless steel welds at elevated service temperatures or during post weld heat treatment (PWHT), especially within the heat-affected zone (HAZ). This work focuses on the characterization of SRC susceptibility within 347H physically simulated arc welded HAZ at elevated temperatures. A four-step SRC thermomechanical test in combination with finite element modeling (FEM) of the welding and testing processes is developed to establish a susceptibility map for HAZ. The test first runs a thermal cycle with three different peak temperatures (1335, 1275, and 1150 °C) to duplicate representative HAZ subzone microstructures, followed by time-to-failure examination under a variety of pre-stress (260–600 MPa) and pre-strain conditions (0.03–0.19) as a function of reheat temperatures between 750 and 1050 °C. With the aid of FEM, SRC susceptibility maps are generated to identify the threshold stress, plastic strain, and creep strain as a function of test temperature. It was found out that HAZ subzone with a lower peak temperature (1150 °C) appears to be slightly less susceptible to SRC than the other two subzones that experienced higher peak temperatures. Generally, time-to-fracture reduces with increasing initially applied stress and strain for all test temperatures. The pre-stress thresholds decrease from about 500 to 330 MPa as the testing temperature increases from 800 to 1050 °C, while the corresponding initial plastic strain thresholds reduces from 0.15 to 0.06. The SRC susceptibility was also evaluated through the Larson–Miller Parameter (LMP) analysis as a function of plastic strain, initial stress and starting stress upon reaching the testing temperature, respectively. The 1050 °C test with a high pre-applied strain (0.1) exhibits an extremely short time to failure (t = 3 s) that lies outside the general trend in LMP analysis. Additionally, it was identified that a plastic strain above 0.07 is identified to significantly reduce the bulk creep strain tolerance to fracture and therefore increases SRC susceptibility. Hardness measurement and fractography analysis indicated that the strain aging of niobium carbonitrides and other potential phases in conjunction with intergranular precipitates contributes to an increase in microhardness and increased intergranular cracking susceptibility.

Abstract Background Scientific research ability (SRA) is very important for clinical postgraduates. However, the factors affecting students' SRA are constantly changing with the development of medicine. The aim of this study was to investigate the current situation of SRA in clinical postgraduates and exploring the potential factors and the corresponding countermeasures under the background of new medical science. Methods A total of 133 postgraduates (first- or second-year) were investigated by questionnaire in the Second Affiliated Hospital of Fujian Medical University. All results were analyzed by R software. Results In terms of the SRA, academic-degree postgraduate students (ADPSs) were significantly better than professional-degree postgraduate students (PDPSs) (P = 0.001), the students with scientific research interest were remarkably better than those without scientific research interest (P = 0.004), the students who mastered statistical analysis methods were more prominent than those who did not (P = 0.007), the students with paper-writing skills were obviously superior to those without it (P = 0.003), and the second-year students were notably better than the first-year students (P = 0.003). Stratified analysis by the above factors except the degree type showed no significant difference in the first-year postgraduates. In the second-year postgraduates, the ADPSs were remarkably superior to the PDPSs (P = 0.002), the students with scientific research interest were obviously better than those without scientific research interest (P = 0.014), the students with more time investment in scientific research were more prominent than those with less time investment in scientific research (P = 0.025), the students with paper-writing skills were notably superior to those without it (P = 0.031), and the students with plotting ability were better than those without it (P = 0.013). Conclusion The important factors affecting the SRA of clinical postgraduates include the degree type, the grade of student, scientific research interest, time investment in scientific research, statistical analysis methods, paper-writing skills, plotting ability. In short, earlier systematic SRA training contributes to the improvement of SRA in clinical postgraduates, especially in PDPSs.

With the rapid development, microelectronic technology has put forward strict requirements for electronic packaging materials (EPMs). SiCp/Al composites with high volume fraction of SiC has become an ideal candidate for EPMs due to their superior properties including high thermal conductivity, tailorable coefficient of thermal expansion as well as low density in many fields. This study reviewed the manufacturing process of SiCp/Al composites in recent years. In addition, the interface between particle and matrix, the application, and the development trend of SiCp/Al composites has also been summarized.

BackgroundA number of recent observational studies have indicated a correlation between the constitution of gut microbiota and the incidence of pancreatitis. Notwithstanding, observational studies are unreliable for inferring causality because of their susceptibility to confounding, bias, and reverse causality, the causal relationship between specific gut microbiota and pancreatitis is still unclear. Therefore, our study aimed to investigate the causal relationship between gut microbiota and four types of pancreatitis.MethodsAn investigative undertaking encompassing a genome-wide association study (GWAS) comprising 18,340 participants was undertaken with the aim of discerning genetic instrumental variables that exhibit associations with gut microbiota, The aggregated statistical data pertaining to acute pancreatitis (AP), alcohol-induced AP (AAP), chronic pancreatitis (CP), and alcohol-induced CP (ACP) were acquired from the FinnGen Consortium. The two-sample bidirectional Mendelian randomization (MR) approach was utilized. Utilizing the Inverse-Variance Weighted (IVW) technique as the cornerstone of our primary analysis. The Bonferroni analysis was used to correct for multiple testing, In addition, a number of sensitivity analysis methodologies, comprising the MR-Egger intercept test, the Cochran’s Q test, MR polymorphism residual and outlier (MR-PRESSO) test, and the leave-one-out test, were performed to evaluate the robustness of our findings.ResultsA total of 28 intestinal microflora were ascertained to exhibit significant associations with diverse outcomes of pancreatitis. Among them, Class Melainabacteria (OR = 1.801, 95% CI: 1.288–2.519, p = 0.008) has a strong causality with ACP after the Bonferroni-corrected test, in order to assess potential reverse causation effects, we used four types of pancreatitis as the exposure variable and scrutinized its impact on gut microbiota as the outcome variable, this analysis revealed associations between pancreatitis and 30 distinct types of gut microflora. The implementation of Cochran’s Q test revealed a lack of substantial heterogeneity among the various single nucleotide polymorphisms (SNP).ConclusionOur first systematic Mendelian randomization analysis provides evidence that multiple gut microbiota taxa may be causally associated with four types of pancreatitis disease. This discovery may contribute significant biomarkers conducive to the preliminary, non-invasive identification of Pancreatitis. Additionally, it could present viable targets for potential therapeutic interventions in the disease’s treatment.

Objective Esophageal varix (EV) bleeding is a particularly serious complications of cirrhosis. Prediction of EV bleeding requires extensive endoscopy experience; it remains unreliable and inefficient. This retrospective cohort study evaluated the feasibility of using deep learning (DL) to predict the 12-month risk of EV bleeding based on endoscopic images. Methods Six DL models were trained to perform binary classification of endoscopic images of EV bleeding. The models were subsequently validated using an external test dataset, then compared with classifications performed by two endoscopists. Results In the validation dataset, EfficientNet had the highest accuracy (0.910), followed by ConvMixer (0.898) and Xception (0.875). In the test dataset, EfficientNet maintained the highest accuracy (0.893), which was better than the endoscopists (0.800 and 0.763). Notably, one endoscopist displayed higher recall (0.905), compared with EfficientNet (0.870). When their predictions were assisted by artificial intelligence, the accuracies of the two endoscopists increased by 17.3% and 19.0%. Moreover, statistical agreement among the models was dependent on model architecture. Conclusions This study demonstrated the feasibility of using DL to predict the 12-month risk of EV bleeding based on endoscopic images. The findings suggest that artificial intelligence-aided diagnosis will be a useful addition to cirrhosis management.

Diabetic retinopathy (DR) is a severe microvascular complication of diabetes mellitus and a major cause of blindness in young adults. Multiple potential factors influence DR; however, the exact mechanisms are poorly understood. Advanced treatments for DR, including laser therapy, vitrectomy, and intraocular drug injections, slow the disease’s progression but fail to cure or reverse visual impairment. Therefore, additional effective methods to prevent and treat DR are required. The biological clock plays a crucial role in maintaining balance in the circadian rhythm of the body. Poor lifestyle habits, such as irregular routines and high-fat diets, may disrupt central and limbic circadian rhythms. Disrupted circadian rhythms can result in altered glucose metabolism and obesity. Misaligned central and peripheral clocks lead to a disorder of the rhythm of glucose metabolism, and chronically high sugar levels lead to the development of DR. We observed a disturbance in clock function in patients with diabetes, and a misaligned clock could accelerate the development of DR. In the current study, we examine the relationship between circadian rhythm disorders, diabetes, and DR. We conclude that: 1) abnormal function of the central clock and peripheral clock leads to abnormal glucose metabolism, further causing DR and 2) diabetes causes abnormal circadian rhythms, further exacerbating DR. Thus, our study presents new insights into the prevention and treatment of DR.

Abstract Background Diabetic retinopathy is a sight-threatening ocular complication of diabetes. Screening is an effective way to reduce severe complications, but screening attendance rates are often low, particularly for newcomers and immigrants to Canada and people from cultural and linguistic minority groups. Building on previous work, in partnership with patient and health system stakeholders, we co-developed a linguistically and culturally tailored tele-retinopathy screening intervention for people living with diabetes who recently immigrated to Canada from either China or African-Caribbean countries. Methods Following an environmental scan of diabetes eye care pathways in Ottawa, we conducted co-development workshops using a nominal group technique to create and prioritize personas of individuals requiring screening and identify barriers to screening that each persona may face. Next, we used the Theoretical Domains Framework to categorize the barriers/enablers and then mapped these categories to potential evidence-informed behaviour change techniques. Finally with these techniques in mind, participants prioritized strategies and channels of delivery, developed intervention content, and clarified actions required by different actors to overcome anticipated intervention delivery barriers. Results We carried out iterative co-development workshops with Mandarin and French-speaking individuals living with diabetes (i.e., patients in the community) who immigrated to Canada from China and African-Caribbean countries (n = 13), patient partners (n = 7), and health system partners (n = 6) recruited from community health centres in Ottawa. Patients in the community co-development workshops were conducted in Mandarin or French. Together, we prioritized five barriers to attending diabetic retinopathy screening: language (TDF Domains: skills, social influences), retinopathy familiarity (knowledge, beliefs about consequences), physician barriers regarding communication for screening (social influences), lack of publicity about screening (knowledge, environmental context and resources), and fitting screening around other activities (environmental context and resources). The resulting intervention included the following behaviour change techniques to address prioritized local barriers: information about health consequence, providing instructions on how to attend screening, prompts/cues, adding objects to the environment, social support, and restructuring the social environment. Operationalized delivery channels incorporated language support, pre-booking screening and sending reminders, social support via social media and community champions, and providing using flyers and videos as delivery channels. Conclusion Working with intervention users and stakeholders, we co-developed a culturally and linguistically relevant tele-retinopathy intervention to address barriers to attending diabetic retinopathy screening and increase uptake among two under-served groups.

Palm oil industry is an important economic resource for Malaysia. However, an oil palm tree disease called Basal Stem Rot has impeded the production of palm oil, which caused significant economic loss at the same time. The oil palm tree disease is caused by a fungus known as Ganoderma Boninense. Infected trees often have little to no symptoms during early stage of infection, which made early detection difficult. Early disease detection is necessary to allow early sanitization and disease control efforts. Using Terrestrial Laser Scanning technology, 88 grey-distribution canopy images of oil palm tree were obtained. The images were pre-processed and augmented before being used for training and testing of the deep learning models. The capabilities of the Convolution Neural Network deep learning models in the classification of dataset into healthy and non-healthy class were tested and the best performing model was identified based on the Macro-F1 score. Fine-tuned DenseNet121 model was the best performing model, recorded a Macro F1-score of 0.798. It was also noted that Baseline model showed a relatively remarkable macro-F1 score of 0.747, which was better than all the feature extractor models and some of the fine-tuned models. However, fine-tuned models suffered from model overfitting due to dataset limitations. For future work, it is recommended to increase the sample size and utilize other CNN architectures to improve the model performance and progress towards detecting Basal Stem Rot at the early stage of infection by classifying sample images into multiple classes.

Abstract Background Polycystic ovary syndrome (PCOS) is currently considered to have a peri-adolescence onset and continuously influence the reproductive and metabolic health of the patients, while the diagnostic criteria among adolescent population haven’t been universally unified till now. This survey seeks to preliminarily evaluate the prevalence of PCOS in the tenth grade schoolgirls in Guangzhou area under NIH criteria and analyze the clinical features of adolescents with PCOS. Methods The cross-sectional epidemiological survey was carried out among the tenth grade schoolgirls in Guangzhou area by the method of cluster sampling. The contents of this survey included the questionnaire, physical exams and serum measurements. Until now, totally 1294 girls underwent this survey and 1095 serum samples were restored. 235 non-hirsute (mFG 2 years after menarche. Among the 235 healthy girls, the 95th percentile values of Testosterone (T), Free androgen index (FAI) and Androstenedione (A2) were 2.28 nmol/mL, 4.37, and 5.20 nmol/mL respectively. Based on the NIH criteria, the prevalence of PCOS in this survey was 3.86%. The prevalence of adolescent PCOS tend to slightly increase with age and gynecological age, but the difference was not statistically significant. The prevalence of PCOS among obese girls was markedly higher than that in lean girls. Conclusion Based on the NIH criteria, the prevalence of PCOS among the tenth grade schoolgirls in Guangzhou area was 3.86%. The diagnosis of hyperandrogenism among adolescents should also be based on both clinical and biochemical parameters.

The overuse of fertilizers in open-field tomato leads to soil deterioration through nutrient leaching and increases the risk of agricultural non-point source contamination. Currently, the combined effects of different fertilization methods on soil nitrogen leaching and tomato production are still unclear. Therefore, the most effective fertilization method for open-field tomato should be discovered by examining how different fertilization methods affected tomato yield and quality, nitrogen use efficiency (NUE), and soil nitrogen leaching. Compared with CK (no fertilization), fertilization significantly increased the yield, total sugar (TS), total soluble solids (TSS), and vitamin C (vC) contents of fruits (p < 0.05), and OPT (optimal fertilization, controlled release nitrogen application, 240 kg ha−1) had the largest effect on increasing yield, quality, and net profit. However, when the fertilizer application rate reached 375 kg ha−1, these indices decreased. Nitrogen leaching concentrations, leaching amount, and titratable acids (TAs) increased with increased nitrogen application rates. Compared with other treatments, OPT reduced the total leaching amounts of total nitrogen (TN), nitrate nitrogen (NO3−-N), and ammonia nitrogen (NH4+-N) by 30.09–51.79%, 24.89–50.03%, and 30–65%, respectively. Principal component analysis (PCA) showed that OPT achieved the highest overall score in terms of yield, quality, and nitrogen leaching conditions. The partial least squares path modeling (PLS-PM) further reveals that applications of high amounts of nitorigen have a positive effect on soil nitrogen leaching. The amount of nitrogen leaching vegetatively affects tomato yield and quality, while plant uptake of nitrogen positively affects tomato production. These findings confirm the importance of using controlled-release fertilizers and reducing nitrogen inputs to control nitrogen leaching and enhance open-field tomato yields.

Evaluating the carbon storage of forests and identifying the factors that influence it are essential in working towards the “dual carbon” goal. This assessment will facilitate research on carbon neutrality and promote regional ecological protection and development. This study utilized the “One Map” data of forest resources (2020) and the first year (2017) of the establishment of the national park in Wuyi Mountain National Park (WMNP). The continuous biomass expansion factor method, in conjunction with the vegetation carbon content coefficient, was employed to estimate the forest carbon storage within the park’s forested areas. Subsequently, the distribution of forest carbon storage was analyzed using remote sensing estimation methods, and a comparison was made between the forest carbon storage of these two years. Finally, correlation analysis and path analysis were conducted to identify the primary factors influencing forest carbon storage. The study findings reveal that in 2020, the total carbon storage in forests reached 4.851 × 106 t C, with an average carbon density of 49.55 t C·hm−2. Furthermore, the study identified positive correlations between dominant tree species, age groups, and elevation with carbon storage, whereas slope length and aspect were found to have negative correlations. Dominant tree species were observed to have the greatest impact on forest carbon storage in both 2017 and 2020, followed by age groups. These findings offer valuable scientific insights for the implementation of forest carbon storage pilot projects in WMNP.

Negative air ions (NAIs) are crucial for assessing the impact of forests on wellbeing and enhancing the physical and mental health of individuals. They serve as pivotal indicators for assessing air quality. Comprehensive research into the distribution patterns of NAI concentrations, especially the correlation between NAI concentrations and meteorological elements in tourist environments, necessitates the accumulation of additional long-term monitoring data. In this paper, long-term on-site monitoring of NAI concentrations, air temperature, relative humidity, and other factors was conducted in real time over 24 h, from April 2020 to May 2022, to explore the temporal dynamic patterns of NAIs and their influencing factors. The results showed that (1) the daily dynamics of NAI concentrations followed a U-shaped curve. The peak concentrations usually occurred in the early morning (4:30–8:00) and evening (19:10–22:00), and the lowest concentrations usually occurred at noon (12:50–14:45). (2) At the monthly scale, NAI concentrations were relatively high in February, August, and September and low in January, June, and December. At the seasonal scale, NAI concentrations were significantly higher in winter than in other seasons, with higher concentrations occurring in the summer and autumn. (3) Relative humidity, air temperature, and air quality index (AQI) were the primary factors that influenced NAI concentrations. Relative humidity showed a significant positive correlation with NAI concentrations, while air temperature and AQI both exhibited a significant negative correlation with NAI concentrations. Higher air quality corresponds to higher NAI concentrations. Our research provides new insights into NAI temporal dynamics patterns and their driving factors, and it will aid in scheduling outdoor recreation and forest health activities.

Accelerating the in-depth integration of media to achieve high-quality development in the media industry has become important for China's cultural media. We built a high-quality development index system for China's media sector and used financial data from A-share media industry listed companies from 2017 to 2020 to measure the high-quality development index of China's media business using the Global Malmquist-Luenberger production function method with the framework of the SBM model degree. We used the generalised method of moments model and the single-threshold model to estimate the threshold value of the media convergence degree and its factor distortions. Deep media integration can promote high-quality development in the media sector. However, insufficient and unbalanced development of media integration is the main hindrance to China's high-quality development of its media.

Appropriate image preprocessing could improve machine learning performance, but the robustness of machine learning to preprocessing methods in micrograph datasets with significant sample differences remains unexplored. Here we collected hundreds of optical micrographs varied in color, contrast, size and brightness and tensile strength from published literature. After preprocessing including color transformation, size adjustment, normalization and image enhancement, classification model of whether it was texture or not and tensile strength prediction model were established using transfer learning and VGG16 model. Our results showed comparable accuracy between classification models using grayscale and color micrographs. Based on grayscale images, classification model utilizing center cropping achieved an average accuracy 1.09% higher than model employing scaling, while coefficient of determination (R2) of regression model showed an average increase of 0.0404. The combination of cropping and dividing by 255 was preferable for classification model, yielding an accuracy of 90.79%. Similarly, the combination of cropping and min–max normalization had a better effect on regression model, yielding R2 of 0.2167. Histogram equalization emerged as the optimal technique for improving classification model, yielding 2.63% increase in accuracy compared to models without image enhancement. For regression models, gamma correction exhibited the highest improvement effect, with an R2 of 0.2681.