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Abstract Objective We aimed to analyze the relationship between non-alcoholic fatty liver and progressive fibrosis and serum 25-hydroxy vitamin D (25(OH)D) in patients with type 2 diabetes mellitus. Methods A total of 184 patients with T2DM who were hospitalized in the Department of Endocrinology of the ShiDong Clinical Hospital between January 2023 and June 2023 were selected. We compared review of anthropometric, biochemical, and inflammatory parameters and non-invasive scores between groups defined by ultrasound NAFLD severity grades.We determine the correlation between 25(OH)D and FLI and FIB-4 scores, respectively. Results Statistically significant differences were seen between BMI, WC, C-peptide levels, FPG, ALT, serum 25(OH)D, TC, HDL, lumbar spine bone density, FLI, and FIB-4 in different degrees of NAFLD. Multivariate logistic regression analysis showed that 25(OH)D (OR = 1.26, p = 0.001), age (OR = 0.93, P

Abstract Salvia miltiorrhiza is commonly used as a Chinese herbal medicine to treat different cardiovascular and cerebrovascular illnesses due to its active ingredients. Environmental conditions, especially drought stress, can affect the yield and quality of S. miltiorrhiza. However, moderate drought stress could improve the quality of S. miltiorrhiza without significantly reducing the yield, and the mechanism of this initial drought resistance is still unclear. In our study, transcriptome and metabolome analyses of S. miltiorrhiza under different drought treatment groups (CK, A, B, and C groups) were conducted to reveal the basis for its drought tolerance. We discovered that the leaves of S. miltiorrhiza under different drought treatment groups had no obvious shrinkage, and the malondialdehyde (MDA) contents as well as superoxide dismutase (SOD) and peroxidase (POD) activities dramatically increased, indicating that our drought treatment methods were moderate, and the leaves of S. miltiorrhiza began to initiate drought resistance. The morphology of root tissue had no significant change under different drought treatment groups, and the contents of four tanshinones significantly enhanced. In all, 5213, 6611, and 5241 differentially expressed genes (DEGs) were shared in the A, B, and C groups compared with the CK group, respectively. The results of KEGG and co-expression analysis showed that the DEGs involved in plant-pathogen interactions, the MAPK signaling pathway, phenylpropanoid biosynthesis, flavonoid biosynthesis, and plant hormone signal transduction responded to drought stress and were strongly correlated with tanshinone biosynthesis. Furthermore, the results of metabolism analysis indicated that 67, 72, and 92 differentially accumulated metabolites (DAMs), including fumarate, ferulic acid, xanthohumol, and phytocassanes, which were primarily involved in phenylpropanoid biosynthesis, flavonoid biosynthesis, and diterpenoid biosynthesis pathways, were detected in these groups. These discoveries provide valuable information on the molecular mechanisms by which S. miltiorrhiza responds to drought stress and will facilitate the development of drought-resistant and high-quality S. miltiorrhiza production.

Abstract The mechanism and function of the expression of Schwann characteristics by nevus cells in the mature zone of the dermis are unknown. Early growth response 3 (EGR3) induces Schwann cell‐like differentiation of melanoma cells by simulating the process of nevus maturation, which leads to a strong phenotypic transformation of the cells, including the formation of long protrusions and a decrease in cell motility, proliferation, and melanin production. Meanwhile, EGR3 regulates the levels of myelin protein zero (MPZ) and collagen type I alpha 1 chain (COL1A1) through SRY‐box transcription factor 10 (SOX10)‐dependent and independent mechanisms, by binding to non‐strictly conserved motifs, respectively. Schwann cell‐like differentiation demonstrates significant benefits in both in vivo and clinical studies. Finally, a CD86‐P2A‐EGR3 recombinant mRNA vaccine is developed which leads to tumor control through forced cell differentiation and enhanced immune infiltration. Together, these data support further development of the recombinant mRNA as a treatment for cancer.

Abstract Background Venom systems are ideal models to study genetic regulatory mechanisms that underpin evolutionary novelty. Snake venom glands are thought to share a common origin, but there are major distinctions between venom toxins from the medically significant snake families Elapidae and Viperidae, and toxin gene regulatory investigations in elapid snakes have been limited. Here, we used high-throughput RNA-sequencing to profile gene expression and microRNAs between active (milked) and resting (unmilked) venom glands in an elapid (Eastern Brown Snake, Pseudonaja textilis), in addition to comparative genomics, to identify cis- and trans-acting regulation of venom production in an elapid in comparison to viperids (Crotalus viridis and C. tigris). Results Although there is conservation in high-level mechanistic pathways regulating venom production (unfolded protein response, Notch signaling and cholesterol homeostasis), there are differences in the regulation of histone methylation enzymes, transcription factors, and microRNAs in venom glands from these two snake families. Histone methyltransferases and transcription factor (TF) specificity protein 1 (Sp1) were highly upregulated in the milked elapid venom gland in comparison to the viperids, whereas nuclear factor I (NFI) TFs were upregulated after viperid venom milking. Sp1 and NFI cis-regulatory elements were common to toxin gene promoter regions, but many unique elements were also present between elapid and viperid toxins. The presence of Sp1 binding sites across multiple elapid toxin gene promoter regions that have been experimentally determined to regulate expression, in addition to upregulation of Sp1 after venom milking, suggests this transcription factor is involved in elapid toxin expression. microRNA profiles were distinctive between milked and unmilked venom glands for both snake families, and microRNAs were predicted to target a diversity of toxin transcripts in the elapid P. textilis venom gland, but only snake venom metalloproteinase transcripts in the viperid C. viridis venom gland. These results suggest differences in toxin gene posttranscriptional regulation between the elapid P. textilis and viperid C. viridis. Conclusions Our comparative transcriptomic and genomic analyses between toxin genes and isoforms in elapid and viperid snakes suggests independent toxin regulation between these two snake families, demonstrating multiple different regulatory mechanisms underpin a venomous phenotype.

Abstract Background Toxoplasma gondii is an important protozoan pathogen with medical and veterinary importance worldwide. Drugs currently used for treatment of toxoplasmosis are less effective and sometimes cause serious side effects. There is an urgent need for the development of more effective drugs with relatively low toxicity. Methods The effect of tylosin on the viability of host cells was measured using CCK8 assays. To assess the inhibition of tylosin on T. gondii proliferation, a real-time PCR targeting the B1 gene was developed for T. gondii detection and quantification. Total RNA was extracted from parasites treated with tylosin and then subjected to transcriptome analysis by RNA sequencing (RNA-seq). Finally, murine infection models of toxoplasmosis were used to evaluate the protective efficacy of tylosin against T. gondii virulent RH strain or avirulent ME49 strain. Results We found that tylosin displayed low host toxicity, and its 50% inhibitory concentration was 175.3 μM. Tylsoin also inhibited intracellular T. gondii tachyzoite proliferation, with a 50% effective concentration of 9.759 μM. Transcriptome analysis showed that tylosin remarkably perturbed the gene expression of T. gondii, and genes involved in “ribosome biogenesis (GO:0042254)” and “ribosome (GO:0005840)” were significantly dys-regulated. In a murine model, tylosin treatment alone (100 mg/kg, i.p.) or in combination with sulfadiazine sodium (200 mg/kg, i.g.) significantly prolonged the survival time and raised the survival rate of animals infected with T. gondii virulent RH or avirulent ME49 strain. Meanwhile, treatment with tylosin significantly decreased the parasite burdens in multiple organs and decreased the spleen index of mice with acute toxoplasmosis. Conclusions Our findings suggest that tylosin exhibited potency against T. gondii both in vitro and in vivo, which offers promise for treatment of human toxoplasmosis. Graphical Abstract

Abstract Electroencephalography (EEG) is a non-invasive measurement method for brain activity. Due to its safety, high resolution, and hypersensitivity to dynamic changes in brain neural signals, EEG has aroused much interest in scientific research and medical fields. This article reviews the types of EEG signals, multiple EEG signal analysis methods, and the application of relevant methods in the neuroscience field and for diagnosing neurological diseases. First, three types of EEG signals, including time-invariant EEG, accurate event-related EEG, and random event-related EEG, are introduced. Second, five main directions for the methods of EEG analysis, including power spectrum analysis, time–frequency analysis, connectivity analysis, source localization methods, and machine learning methods, are described in the main section, along with different sub-methods and effect evaluations for solving the same problem. Finally, the application scenarios of different EEG analysis methods are emphasized, and the advantages and disadvantages of similar methods are distinguished. This article is expected to assist researchers in selecting suitable EEG analysis methods based on their research objectives, provide references for subsequent research, and summarize current issues and prospects for the future.

Abstract Objective In the treatment of resectable pancreatic cancer, adjuvant chemotherapy is viewed as essential. However, it is yet unclear how well adjuvant chemotherapy works at different illness stages. This study aims to investigate the efficacy of adjuvant chemotherapy in various pancreatic cancer stages. Materials and methods Patients with pancreatic cancer who underwent surgical intervention at Sun Yat-sen University Cancer Center between January 2018 and January 2021 were included in this retrospective analysis. Results 168 patients were divided into two groups: the group receiving adjuvant chemotherapy (AC) and the group receiving independent surgery (no-AC). Survival analysis reveals that among stage I patients, the AC group demonstrates significant superiority over the no-AC group in terms of recurrence-free survival (RFS) and overall survival (OS) (P = 0.0028; P = 0.022). While there was no discernible difference in RFS between the AC and no-AC groups for patients with stage II illness (P = 0.69), the AC group significantly outperformed the no-AC group in terms of OS (P = 0.047). There was no discernible difference in RFS or OS between the AC and no-AC groups for patients with stage III pancreatic cancer (P = 0.40 and P = 0.20, respectively). Conclusions The administration of adjuvant chemotherapy has been shown to improve the prognosis of patients diagnosed with stage I and II pancreatic cancer. However, its efficacy is limited in individuals with stage III pancreatic cancer. Therefore, there is an urgent need to investigate and develop more effective therapeutic options for patients in the advanced stage.

Abstract Aim To provide a systematic review of the qualitative literature on self‐reported barriers to self‐management in pregnant women with gestational diabetes mellitus (GDM). Design Systematic review. Methods This systematic review followed the Joanna Briggs Institute meta‐aggregation approach and was evaluated using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research. Qualitative studies on the barriers to self‐management among GDM pregnancy survivors conducted until 17 May 2022, were searched. Results A total of 30 studies were included, of which seven were in Chinese and 23 were in English, and 10 findings resulted in three themes: (a) Knowledge and belief, (b) Skills and abilities and (c) Environment and social support. By summarizing the self‐reported barriers to self‐management in patients with GDM and recommends precise interventions for these barriers, thereby saving health resources and helping to increase their willingness and ability to engage in self‐management.

Viral infections can alter host transcriptomes by manipulating host splicing machinery. Despite intensive transcriptomic studies on SARS-CoV-2, a systematic analysis of alternative splicing (AS) in severe COVID-19 patients remains largely elusive. Here we integrated proteomic and transcriptomic sequencing data to study AS changes in COVID-19 patients. We discovered that RNA splicing is among the major down-regulated proteomic signatures in COVID-19 patients. The transcriptome analysis showed that SARS-CoV-2 infection induces widespread dysregulation of transcript usage and expression, affecting blood coagulation, neutrophil activation, and cytokine production. Notably, CD74 and LRRFIP1 had increased skipping of an exon in COVID-19 patients that disrupts a functional domain, which correlated with reduced antiviral immunity. Furthermore, the dysregulation of transcripts was strongly correlated with clinical severity of COVID-19, and splice-variants may contribute to unexpected therapeutic activity. In summary, our data highlight that a better understanding of the AS landscape may aid in COVID-19 diagnosis and therapy.

Shrinkage cracks are some of the most common defects in timber structures obtained from woods with an uneven distribution of moisture content and are subject to external dynamic environmental changes. To accurately predict the changes in the moisture content of wood components at any time and position, this study first applied the principles of food drying and established a moisture field model for laminated wood based on the analogy between heat and humidity transfer. A model for predicting the moisture content of wood that considers time and spatial distribution was then proposed. Second, by collecting relevant experimental data and establishing a finite element analysis model, three moisture absorption conditions (0–9.95%, 0–13.65%, and 0–17.91%) and four desorption conditions (34–5.5%, 28–8.3%, 31–11.8%, and 25.5–15.9%) were analyzed. In the moisture absorption comparison, the time needed to reach 95% equilibrium moisture content was 2.43 days, 4.07 days, and 6.32 days. The rate at which the internal components reached equilibrium moisture content exceeded 10 days. The temporal and spatial distribution of wood moisture content revealed the correctness of the proposed wood moisture field model. Finally, the moisture content prediction model was applied in the order of characteristic equation solutions, moisture content gradient difference, and laminated wood size. The results revealed that the established humidity field model can predict the wood moisture content and how it changes over time and in space. Notably, 1–2 orders for the solution of the characteristic equation are recommended when applying the prediction model. The greater the difference in moisture content, the faster the equilibrium moisture content is reached. The moisture content varies greatly based on the component size and position. Notably, the influence of moisture gradient and wood size on the average wood moisture content cannot be ignored.

Objective: To develop a novel diagnostic modality to identify and diagnose stroke in daily life scenarios for improving the therapeutic effects and prognoses of patients. Methods: In this study, 16 stroke patients and 24 age-matched healthy participants as controls were recruited for comparative analysis. Leveraging a portable eye-tracking device and integrating traditional Chinese medicine theory with modern color psychology principles, we recorded the eye movement signals and calculated eye movement features. Meanwhile, the stroke recognition models based on eye movement features were further trained by using random forest (RF), k-nearest neighbors (KNN), decision tree (DT), gradient boosting classifier (GBC), XGBoost, and CatBoost. Results: The stroke group and the healthy group showed significant differences in some eye movement features (P

Many different chicken breeds are found around the world, their features vary among them, and they are valuable resources. Currently, there is a huge lack of knowledge of the genetic determinants responsible for phenotypic and biochemical properties of these breeds of chickens. Understanding the underlying genetic mechanisms that explain across-breed variation can help breeders develop improved chicken breeds. The whole-genomes of 140 chickens from 7 Shandong native breeds and 20 introduced recessive white chickens from China were re-sequenced. Comparative population genomics based on autosomal single nucleotide polymorphisms (SNPs) revealed geographically based clusters among the chickens. Through genome-wide scans for selective sweeps, we identified thyroid stimulating hormone receptor (TSHR, reproductive traits, circadian rhythm), erythrocyte membrane protein band 4.1 like 1 (EPB41L1, body size), and alkylglycerol monooxygenase (AGMO, aggressive behavior), as major candidate breed-specific determining genes in chickens. In addition, we used a machine learning classification model to predict chicken breeds based on the SNPs significantly associated with recourse characteristics, and the prediction accuracy was 92%, which can effectively achieve the breed identification of Laiwu Black chickens. We provide the first comprehensive genomic data of the Shandong indigenous chickens. Our analyses revealed phylogeographic patterns among the Shandong indigenous chickens and candidate genes that potentially contribute to breed-specific traits of the chickens. In addition, we developed a machine learning-based prediction model using SNP data to identify chicken breeds. The genetic basis of indigenous chicken breeds revealed in this study is useful to better understand the mechanisms underlying the resource characteristics of chicken.

Clinical presentation of central nervous system (CNS) infections caused by varicella-zoster virus (VZV) is highly sophisticated, making identification challenging. We retrospectively reported 18 cases of VZV neurologic disease confirmed by metagenomic next-generation sequencing (mNGS). The detection rate of mNGS was higher than that of PCR assay (100 vs 66.7%, p < 0.05) and serum IgM antibody (100 vs 68.8%, p < 0.05) measurement. Of the 18 cases, five patients were diagnosed with acute meningitis, three with acute meningitis combined with facial neuritis, three with acute meningitis combined with polycranial neuritis, and the remaining seven with various clinical diagnoses. Typical clinical symptoms included headache (15), fever (9), and rash (11). Cranial or spinal MRI showed abnormalities in 12 patients, and 17 patients had obvious neurological symptoms. The predominant genotype of VZV in this study was genotype J (100%, 10/10). All patients were treated with acyclovir/penciclovir and dexamethasone, 16 recovered and 2 died. Our study highlights the good performance of mNGS in diagnosing CNS infection caused by VZV. It could provide additional diagnostic evidence in patients with diverse clinical spectrum and variable manifestations.

Background Skeletal muscle mass is an essential parameter for diagnosing sarcopenia. The gold standard for assessing skeletal muscle mass is using computed tomography (CT) to measure skeletal muscle area at the third lumbar vertebra (L3) level. This study aims to investigate whether skeletal muscle mass could be evaluated at the first lumbar vertebra (L1) level using images obtained from routine chest CT scans. Methods Skeletal muscle index (SMI, cm2/m2) and skeletal muscle density (SMD, HU) are commonly used to measure relative muscle mass and the degree of fat infiltration. This study used CT images at the L1 level to measure the skeletal muscle area (SMA, cm2) in 815 subjects from the health examination center. Linear regression analysis was used to explore the association between L1 and L3 measurements. The receiver operating characteristic (ROC) analysis was used to assess the predictive performance of L1 SMI for sarcopenia. The sex-specific cut-off values for low skeletal muscle mass in patients under the age of 60 were determined using the following formula: “mean − 1.28 × standard deviation.” A multivariate linear regression model was established. Results A significantly higher SMI at the L1 level was found in males than in females (43.88 ± 6.33 cm2/m2 vs 33.68 ± 5.03 cm2/m2; P < 0.001). There were strong correlations between measures at the L1 and L3 levels in both the total subject and sex-specific analyses. A negative association was found between age and L3 SMI in males (r = −0.231, P = 0.038). Both body mass index (BMI) and body surface area (BSA) were positively associated with L1 SMI in both males and females. A multivariate analysis was used to establish a prediction rule to predict SMI at the L3 level. The assessment of consistency and interchangeability between predicted and actual SMI at the L3 level yielded moderately good results. Considering the significant differences observed between male and female participants, the sex-specific cut-off values of the L1 SMI for defining low skeletal muscle mass were 36.52 cm2/m2 in males and 27.29 cm2/m2 in females. Conclusions Based on a population from central China, the correlated indicators obtained at the L1 level from routine chest CT scans may serve as effective surrogate markers for those at the L3 level in assessing overall skeletal muscle mass.