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Abstract Objectives Pulmonary neuroendocrine neoplasms (NENs) are the most frequent cause of ectopic adrenocorticotropic hormone syndrome (EAS); lung infection is common in EAS. An imaging finding of infection in EAS patients can mimic NENs. This retrospective study investigated EAS-associated pulmonary imaging indicators. Methods Forty-five pulmonary NENs and 27 tumor-like infections from 59 EAS patients (45 NEN and 14 infection patients) were included. Clinical manifestations, CT features, 18F-FDG, or 68Ga-DOTATATE-PET/CT images and pathological results were collected. Results High-sensitivity C-reactive protein (p

Abstract Objective This study aimed at evaluating the effects of online and offline hybrid weight management approach based on the Fogg behavior model on total gestational weight gain and perinatal outcomes. Methods Pregnant women in Hainan, the southernmost province of China, were recruited into a randomized controlled trial, which was designed to develop a WeChat platform for pregnancy weight management, and implement individualized and continuous pregnancy weight management services for pregnant women under the guidance of the Fogg behavior model. All pregnant women participating in the study were included in the full analysis set (FAS) for analysis. The pregnant women who completed the intervention and provided all outcome indicators were included in the per protocol set (PPS) for outcome evaluation. Results Fifty-eight pregnant women were included in FAS analysis, and 52 pregnant women were finally included in PPS analysis. There was no statistically significant difference (P > 0.05) between the two groups at baseline. The gestational weight gain of the intervention group was significantly lower than that of the control group (P

Abstract Background Environmental temperature is critical in regulating biological functions in fish. S. prenanti is a kind of cold-water fish, but of which we have little knowledge about the metabolic adaptation and physiological responses to long-term cold acclimation. Results In this study, we determined the physiological responses of S. prenanti serum after 30 days of exposure to 6℃. Compared with the control group, the levels of TC, TG, and LDL-C in the serum were significantly (P

IntroductionSoil contamination with copper (Cu) threatens ecological security and human health. Rapeseed demonstrates potential in remediating copper-contaminated soil, and biochar-assisted phytoremediation is increasingly being employed to improve remediation efficiency. However, the combined application of them has not been thoroughly studied in terms of the synergistic effects and the mechanisms of their interaction.MethodsIn this regard, this study conducted a pot experiment to evaluate biochar-assisted remediation under Cu-contaminated soil with varying biochar application rates; Furthermore, the plant physiological mechanism and soil physicochemical properties involved in the biocharrapeseed system was explored.ResultsOur results showed that the exchangeable pool of copper in soil decreased by 10.0% and 12.3% with adding 5% biochar (BC1) and 10% biochar (BC2) relative to control (BC0), respectively, prior to rapeseed cultivation. The rapeseed cultivation for one season further reclaimed 4.9%, 9.0%, and 13.6% of the available copper in this soil by root extraction under the BC0, BC1, and BC2 treatments, respectively. The overall copper concentration in plants decreased by 23.7% under BC2 and 13.3% under BC1 compared to BC0. However, the plant’s dry biomass at BC1 and BC2 treatments increased by 1.7-fold and 2.7-fold relative to BC0, which offset the negative impact of the decreased copper concentration on phytoremediation. Physiological analysis showed adding 10% biochar decreased the MDA content by 36% in the leaf and 49% in the root, compared to BC0. The transmission electron microscopy for cell wall ultrastructure in root tips showed that biochar addition in Cu-contaminated soil increased the mechanical strength of the celL wall, explicitly increasing the thickness of the secondary cell wall. Further cell wall components analysis revealed a remarkable increment of the pectin content in BC2 relative to BC0, increased by 56% in the leaf and 99% in the root, respectively. Additionally, 10% biochar application led to a roughly 2-fold increase in seed yield via ameliorating the soil physicochemical properties and increasing the rapeseed growth.DiscussionThese findings offer insights into synergistic rapeseed-biochar use for Cu-contaminated soil remediation.

BackgroundRNA editing, especially A-to-I editing sites, is a common RNA modification critical for stem cell differentiation, muscle development, and disease occurrence. Unveiling comprehensive RNA A-to-I editing events associated with myogenesis of the skeletal muscle satellite cells (MuSCs) is essential for extending our knowledge of the mechanism underpinning muscle development.ResultsA total of 9,632 RNA editing sites (RESs) were screened in the myoblasts (GM), myocytes (DM1), and myotubes (DM5) samples. Among these sites, 4,559 A-to-I edits were classified and further analyzed. There were 3,266 A-to-I sites in the protein-coding region, out of which 113 missense sites recoded protein. Notably, five A-to-I sites in the 3′ UTR of four genes (TRAF6, NALF1, SLC38A1, ENSCHIG00000019092) altered their targeted miRNAs. Furthermore, a total of 370 A-to-I sites with different editing levels were detected, including FBN1, MYH10, GSK3B, CSNK1D, and PRKACB genes. These genes were predominantly enriched in the cytoskeleton in muscle cells, the hippo signaling pathway, and the tight junction. Furthermore, we identified 14 hub genes (TUFM, GSK3B, JAK2, RPSA, YARS1, CDH2, PRKACB, RUNX1, NOTCH2, CDC23, VCP, FBN1, RARS1, MEF2C) that potentially related to muscle development. Additionally, 123 stage-specific A-to-I editing sites were identified, with 43 sites in GM, 25 in DM1, and 55 in DM5 samples. These stage-specific edited genes significantly enriched essential biological pathways, including the cell cycle, oocyte meiosis, motor proteins, and hedgehog signaling pathway.ConclusionWe systematically identified the RNA editing events in proliferating and differentiating goat MuSCs, which was crucial for expanding our understanding of the regulatory mechanisms of muscle development.

Understanding the colonization and change patterns of gut microbiota is pivotal for comprehending host health. As a newly cultured breed, the studies on the gut microbiota of Tianfu goats remain limited. This study aimed to address this gap by analyzing the microbial composition and colonization patterns of fecal samples collected from goat kids from birth to weaning. Fecal samples were collected on days 0, 7, 14, 21, 28, 35, 42, 49, 53, 55, 57, and 64, and the changes and colonization patterns of microorganisms were analyzed through high-throughput 16S rRNA sequencing. The results showed that the abundance of fecal microbiota in goat kids gradually increased over time, followed by a decrease after weaning and stabilization, with reduced individual differences. The colonization of fecal microorganisms mainly presented three different stages: days 0–14, days 21–49, and days 53–64. During the suckling period, the relative abundance of Proteobacteria (72.34%) was the highest, followed by Firmicutes (21.66%). From 21 days old, the microbiota in goat kids gradually to be diverse, with Lachnospiraceae and Ruminococcaceae being dominant. During post-weaning, Ruminococcaceae (30.98–33.34%) was becoming prominence which helpful for cellulose decomposition. LEfSe analyzed three important time points (d0 vs. d7, d7 vs. d14, d49 vs. d53, LDA score > 4 and p

ABSTRACT Background Cornelia de Lange syndrome (CdLS) is an uncommon congenital developmental disorder distinguished by intellectual disorder and distinctive facial characteristics, with a minority of cases attributed to RAD21 variants. Methods A patient was admitted to the endocrinology department at Peking Union Medical College Hospital, where 2 mL of peripheral venous blood was collected from the patient and his parents. DNA was extracted for whole‐exome sequencing (WES) analysis, and the genetic variation of the parents was confirmed through Sanger sequencing. Results A 13.3‐year‐old male patient with a height of 136.5 cm (−3.5 SDS) and a weight of 28.4 kg (−3.1 SDS) was found to have typical craniofacial features. WES revealed a pathogenic variant c.1143G>A (p.Trp381*) in the RAD21 gene. He was diagnosed with CdLS type 4 (OMIM #614701). We reviewed 36 patients with CdLS related to RAD21 gene variants reported worldwide from May 2012 to March 2024. Patient's variant status, clinical characteristics, and rhGH treatment response were summarized. Frameshift variants constituted the predominant variant type, representing 36% (13/36) of cases. Clinical features included verbal developmental delay and intellectual disorder observed in 94% of patients. Conclusion This study reported the third case of CdLS type 4 in China caused by a RAD21 gene variant, enriching the genetic mutational spectrum.

Every-other-day fasting (EODF) is a form of caloric restriction that alternates between periods of normal eating and fasting, aimed at preventing and treating diseases. This approach has gained widespread usage in basic research on neurological conditions, including spinal cord injury, and has demonstrated significant neuroprotective effects. Additionally, EODF is noted for its safety and feasibility, suggesting broad potential for application. This study aims to evaluate the therapeutic effects of EODF on spinal cord injury and to investigate and enhance its underlying mechanisms. Initially, the SCI rat model was utilized to evaluate the effects of EODF on pathological injury and motor function. Subsequently, considering the enhancement of metabolism through EODF, bile acid metabolism in SCI rats was analyzed using liquid chromatography-mass spectrometry (LC–MS), and the expression of the bile acid receptor TGR5 was further assessed. Ultimately, it was confirmed that EODF influences the activation of microglia and NLRP3 inflammasomes associated with the TGR5 signaling, along with the expression of downstream pyroptosis pathway related proteins and inflammatory cytokines, as evidenced by the activation of the NLRP3/Caspase-1/GSDMD pyroptosis pathway in SCI rats. The results demonstrated that EODF significantly enhanced the recovery of motor function and reduced pathological damage in SCI rats while controlling weight gain. Notably, EODF promoted the secretion of bile acid metabolites, activated TGR5, and inhibited the NLRP3/Caspase-1/GSDMD pyroptosis pathway and inflammation in these rats. In summary, EODF could mitigate secondary injury after SCI and foster functional recovery by improving metabolism, activating the TGR5 signaling and inhibiting the NLRP3 pyroptosis pathway.

Abstract Hu sheep (HS), a breed of sheep carrying the FecB mutation gene, is known for its “year-round estrus and multiple births” and is an ideal model for studying the high fecundity mechanisms of livestock. Through analyzing and comparing the genomic selection features of Hu sheep and other sheep breeds, we identified a series of candidate genes that may play a role in Hu sheep’s high fecundity mechanisms. In this study, we conducted whole-genome resequencing on six breeds and screened key mutations significantly correlated with high reproductive traits in sheep. Notably, the CC2D1B gene was selected by the fixation index (F ST) and the cross-population composite likelihood ratio (XP-CLR) methods in HS and other five breeds. It was worth noting that the CC2D1B gene in HS was different from that in other sheep breeds, and seven missense mutations have been identified. Furthermore, the linkage disequilibrium (LD) analysis revealed a strong linkage disequilibrium in this specific gene region. Subsequently, by performing different grouping based on FecB genotypes in Hu sheep, genome-wide selective signal analysis screened several genes related to reproduction, such as BMPR1B and PPM1K. Besides, F ST analysis identified functional genes related to reproductive traits, including RHEB, HSPA2, PPP1CC, HVCN1, and CCDC63. Additionally, a missense mutation was found in the CCDC63 gene and the haplotype was different between the high reproduction (HR) group and low reproduction (LR) group in HS. In summary, we discovered genetic differentiation among six distinct breeding sheep breeds at the whole genome level. Additionally, we identified a set of genes which were associated with reproductive performance in Hu sheep and visualized how these genes differed in different breeds. These findings laid a theoretical foundation for understanding genetic mechanisms behind high prolific traits in sheep.

Objective: Patients with growth hormone deficiency (GHD) with inadequate growth hormone levels are often correlated with nonalcoholic fatty liver disease (NAFLD). However, the potential mechanism of how GHD influences liver function remains obscure. In the present study, we aim to perform hepatic metabolomics in Lewis dwarf rats, which were the standard congenital isolated GH-deficient rat, to evaluate the characterizations of hepatic metabolic profiles and explore their relations with liver functions. Methods: Lewis dwarf homozygous (dw/dw) rats at 37 weeks (five females and five males), and Lewis dwarf heterozygous (dw/+) rats at 37 weeks (five females and five males) were analyzed in our study. Body lengths and weights, liver weights, serum alanine transaminase (ALT), and serum aspartate transaminase (AST) were measured. ELISA and RT-qPCR were used to assess IGF-1 levels in serum and liver, respectively. The non-targeted metabolomics was performed in the livers of dw/+ and dw/dw rats. Differential metabolites were selected according to the coefficient of variation (CV), variable importance in the projection (VIP) > 1, and P < 0.05. Hierarchical clustering of differential metabolites was conducted, and the KEGG database was used for metabolic pathway analysis. Results: The body weights, body lengths, liver weights, and IGF-1 levels in the serum and liver of dw/dw rats were significantly decreased compared with dw/+ rats. Dw/dw rats exhibited more obvious hepatic steatosis accompanied by higher serum ALT and AST levels. Hepatic metabolomics showed that a total of 88 differential metabolites in positive ion mode, and 51 metabolites in negative ion mode were identified. Among them, lysophosphatidylcholine (LPC) 16:2, LPC 18:3, LPC 22:6, fatty acid esters of hydroxy fatty acids (FAHFA)18:1 were significantly decreased, while palmitoyl acid, dehydrocholic acid, and 7-ketolithocholic acid were significantly increased in dw/dw rats compared with dw/+ rats. These seven differential metabolites were significantly associated with phenotypes of rats. Finally, KEGG pathway analysis showed that the arginine and proline metabolism pathway and bile secretion pathway were mainly clustered. Conclusion: Lewis dw/dw rats with congenital isolated growth hormone deficiency (IGHD) showed liver steatosis and abnormal liver function, which could be potentially associated with the distinctive hepatic metabolic profiles.

The hypometabolism induced by fasting has great potential in maintaining health and improving survival in extreme environments, among which thyroid hormone (TH) plays an important role in the adaptation and the formation of new energy metabolism homeostasis during long-term fasting. In the present review, we emphasize the potential of long-term fasting to improve physical health and emergency rescue in extreme environments, introduce the concept and pattern of fasting and its impact on the body’s energy metabolism consumption. Prolonged fasting has more application potential in emergency rescue in special environments. The changes of THs caused by fasting, including serum biochemical characteristics, responsiveness of the peripheral and central hypothalamus-pituitary-thyroid (HPT) axis, and differential changes of TH metabolism, are emphasized in particular. It was proposed that the variability between brain and liver tissues in THs uptake, deiodination activation and inactivation is the key regulatory mechanism for the cause of peripheral THs decline and central homeostasis. While hypothalamic tanycytes play a pivotal role in the fine regulation of the HPT negative feedback regulation during long-term fasting. The study progress of tanycytes on thyrotropin-releasing hormone (TRH) release and deiodination is described in detail. In conclusion, the combination of the decrease of TH metabolism in peripheral tissues and stability in the central HPT axis maintains the basal physiological requirement and new energy metabolism homeostasis to adapt to long-term food scarcity. The molecular mechanisms of this localized and differential regulation will be a key research direction for developing measures for hypometabolic applications in extreme environment.

Abstract The elevation in the optic nerve sheath (ONS) pressure (ONSP) due to microgravity-induced headward fluid shift is the primary hypothesized contributor to SANS. This longitudinal study aims to quantify the axial plane of the optic nerve subarachnoid space area (ONSSA), which is filled with cerebrospinal fluid (CSF) and expands with elevated ONSP during and after head-down tilt (HDT) bed rest (BR). 36 healthy male volunteers (72 eyes) underwent a 90-day strict 6° HDT BR. Without obtaining the pre-HDT data, measurements were performed on days 30, 60, and 90 during HDT and at 6 recovery time points extended to 180-days (R + 180) in a supine position. Portable B-scan ultrasound was performed using the 12 MHz linear array probe binocularly. The measurements of the ONS and the calculation of the ONSSA were performed with ImageJ 1.51 analysis software by two experienced observers in a masked manner. Compared to R + 180, the ONSSA on HDT30, HDT60, and HDT90 exhibited a consistently significant distention of 0.44 mm2 (95% CI: 0.13 to 0.76 mm2, P = 0.001), 0.45 mm2 (95% CI: 0.15 to 0.75 mm2, P = 0.001), and 0.46 mm2 (95% CI: 0.15 to 0.76 mm2, P

This study aimed to identify risk factors associated with infections after Transrectal ultrasound-guided prostate biopsy (TRUSPB) and to analyze the efficacy of preoperative prophylactic antimicrobial administration. A retrospective analysis was conducted on 766 patients who underwent TRUSPB at our hospital from January 2020 to January 2023. Among them, 450 patients were given a three-day prophylactic course of antimicrobial fluoroquinolones before TRUSPB (Group A), while the remaining 316 patients were administered a single dose of 750 mg oral ciprofloxacin 1 h before TRUSPB (Group B). We calculated the incidence of post-TRUSPB infections in both groups and employed a binary logistic regression model to analyze factors influencing post-TRUSPB infections and evaluate the effectiveness of prophylactic antimicrobial use. Among the 766 patients who underwent prostate biopsy, 62 cases (8.1%) developed post-TRUSPB infections, and there was no statistically significant difference in the rate of post-TRUSPB infections and types of infections between Group A and Group B. Blood and urine cultures from all the 62 infected patients were positive, with Escherichia coli being the most commonly detected pathogen, demonstrating a positive detection rate of 100.0% and accounting for 76% of all infections. Logistic regression analysis identified age (Odds ratio (OR) = 1.15, 95% Confidence Interval (CI) 1.05–1.25), a history of diabetes mellitus (OR = 1.31, 95% CI 1.12–1.52), and history of indwelling urinary catheter within 7 days before biopsy (OR = 1.43, 95% CI 1.15–1.77) as risk factors for post-TRUSPB infections. In summary, a single application of ciprofloxacin demonstrated similar efficacy in reducing the risk of post-TRUSPB infection compared to a three-day course of oral fluoroquinolones before biopsy while also reducing the risk of quinolone resistance. Conversely, advanced age, comorbid diabetes mellitus, and a 7-day history of indwelling urinary catheter before TRUSPB increased the risk of post-TRUSPB infection.

As one of the most important economic traits for domestic animal husbandry, skeletal muscle is regulated by an intricate molecular network. Adenosine deaminase acting on RNA (ADAR1) involves various physiological processes and diseases, such as innate immunity and the development of lung adenocarcinoma, breast cancer, gastric cancer, etc. However, its role in skeletal muscle growth requires further clarification. Here, we explored the functions of ADAR1 in the myogenic process of goat skeletal muscle satellite cells (MuSCs). The ADAR1 transcripts were noticeably enriched in goat visceral tissues compared to skeletal muscle. Additionally, its levels in slow oxidative muscles like the psoas major and minor muscles were higher than in the fast oxidative glycolytic and fast glycolytic muscles. Among the two common isoforms from ADAR1, p110 is more abundant than p150. Moreover, overexpressing ADAR1 enhanced the proliferation and myogenic differentiation of MuSCs. The mRNA-seq performed on MuSCs’ knockdown of ADAR1 obtained 146 differentially expressed genes (DEGs), 87 upregulated and 59 downregulated. These DEGs were concentrated in muscle development and process pathways, such as the MAPK and cAMP signaling pathways. Furthermore, many DEGs as the key nodes defined by protein–protein interaction networks (PPI), including STAT3, MYH3/8, TGFβ2, and ACTN4, were closely related to the myogenic process. Finally, RNA immunoprecipitation combined with qPCR (RIP-qPCR) showed that ADAR1 binds to PAX7 and MyoD mRNA. This study indicates that ADAR1 promotes the myogenic development of goat MuSCs, which provides a useful scientific reference for further exploring the ADAR1-related regulatory networks underlying mammal skeletal muscle growth.

Skeletal muscle development is spotlighted in mammals since it closely relates to animal health and economic benefits to the breeding industry. Researchers have successfully unveiled many regulatory factors and mechanisms involving myogenesis. However, the effect of N6-methyladenosine (m6A) modification, especially demethylase and its regulated genes, on muscle development remains to be further explored. Here, we found that the typical demethylase FTO (fat mass- and obesity-associated protein) was highly enriched in goats’ longissimus dorsi (LD) muscles. In addition, the level of m6A modification on transcripts was negatively regulated by FTO during the proliferation of goat skeletal muscle satellite cells (MuSCs). Moreover, a deficiency of FTO in MuSCs significantly retarded their proliferation and promoted the expression of dystrophin-associated protein 1 (DAG1). m6A modifications of DAG1 mRNA were efficiently altered by FTO. Intriguingly, the results of DAG1 levels and its m6A enrichment from FB23-2 (FTO demethylase inhibitor)-treated cells were consistent with those of the FTO knockdown, indicating that the regulation of FTO on DAG1 depended on m6A modification. Further experiments showed that interfering FTO improved m6A modification at site DAG1-122, recognized by Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and consequently stabilized DAG1 transcripts. Our study suggests that FTO promotes the proliferation of MuSCs by regulating the expression of DAG1 through m6A modification. This will extend our knowledge of the m6A-related mechanism of skeletal muscle development in animals.

The process of skeletal muscle development is intricate and involves the regulation of a diverse array of genes. Accurate gene expression profiles are crucial for studying muscle development, making it essential to choose the right reference genes for real-time quantitative PCR (RT-qPCR). In the present study, eight candidate reference genes were identified from our previous transcriptome sequencing analysis of caprine skeletal muscle satellite cells (MuSCs), and two traditional reference genes (ACTB and GAPDH) were assessed. The quantitative levels of the candidate reference genes were determined through the RT-qPCR technique, while the stability of their expression was evaluated utilizing the GeNorm, NormFinder, BestKeeper, and RefFinder programs. Furthermore, the chosen reference genes were utilized for the normalization of the gene expression levels of PCNA and Myf5. It was determined that conventional reference genes, including ACTB and GAPDH, were not appropriate for normalizing target gene expression. Conversely, RPL14 and RPS15A, identified through RNA sequencing analysis, exhibited minimal variability and were identified as the optimal reference genes for normalizing gene expression during the proliferation and differentiation of goat MuSCs. Our research offers a validated panel of optimal reference genes for the detection of differentially expressed genes in goat muscle satellite cells using RT-qPCR.

Domestic animals have multiple phenotypes of skin and coat color, which arise from different genes and their products, such as proteins and metabolites responsible with melanin deposition. However, the complex regulatory network of melanin synthesis remains to be fully unraveled. Here, the skin and tongue tissues of Liangshan black sheep (black group) and Liangshan semi-fine-wool sheep (pink group) were collected, stained with hematoxylin–eosin (HE) and Masson–Fontana, and the transcriptomic and metabolomic data were further analyzed. We found a large deposit of melanin granules in the epidermis of the black skin and tongue. Transcriptome and metabolome analysis identified 744 differentially expressed genes (DEGs) and 443 differentially expressed metabolites (DEMs) between the pink and black groups. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses revealed the DEGs and DEMs were mainly enriched in the pathways of secondary metabolic processes, melanin biosynthesis processes, melanin metabolism processes, melanosome membranes, pigment granule membranes, melanosome, tyrosine metabolism, and melanogenesis. Notably, we revealed the gene ENSARG00020006042 may be a family member of YWHAs and involved in regulating melanin deposition. Furthermore, several essential genes (TYR, TYRP1, DCT, PMEL, MLANA, SLC45A2) were significantly associated with metabolite prostaglandins and compounds involved in sheep pigmentation. These findings provide new evidence of the strong correlation between prostaglandins and related compounds and key genes that regulate sheep melanin synthesis, furthering our understanding of the regulatory mechanisms and molecular breeding of pigmentation in sheep.

Alzheimer’s disease (AD) is a prevalent neurodegenerative disease that has become one of the main factors affecting human health. It has serious impacts on individuals, families, and society. With the development of population aging, the incidence of AD will further increase worldwide. Emerging evidence suggests that many physiological metabolic processes, such as lipid metabolism, are implicated in the pathogenesis of AD. Bile acids, as the main undertakers of lipid metabolism, play an important role in the occurrence and development of Alzheimer’s disease. Tauroursodeoxycholic acid, an endogenous bile acid, has been proven to possess therapeutic effects in different neurodegenerative diseases, including Alzheimer’s disease. This review tries to find the relationship between bile acid metabolism and AD, as well as explore the therapeutic potential of bile acid taurocursodeoxycholic acid for this disease. The potential mechanisms of taurocursodeoxycholic acid may include reducing the deposition of Amyloid-β protein, regulating apoptotic pathways, preventing tau hyperphosphorylation and aggregation, protecting neuronal synapses, exhibiting anti-inflammatory properties, and improving metabolic disorders. The objective of this study is to shed light on the use of tauroursodeoxycholic acid preparations in the prevention and treatment of AD, with the aim of identifying effective treatment targets and clarifying various treatment mechanisms involved in this disease.

ObjectiveTo analyze the relationship between serum complement component 1q (C1q) levels and functional prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH), and to reveal its clinical value.MethodsIn this prospective cohort study, we collected clinical data of aSAH patients admitted to the Department of Neurosurgery, Hangzhou First People’s Hospital from January 2020 to October 2022. Parameters such as serum C1q levels, Hunt-Hess grade, modified Fisher grade, and the modified Rankin scale (mRS) at 3 months were included for evaluation. Patients were grouped based on the occurrence of delayed cerebral ischemia (DCI). Spearman rank correlation test and Kruskal-Wallis rank sum test were used to analyze the correlation between serum C1q levels, disease severity, and prognosis. Potential risk factors affecting prognosis and the occurrence of DCI were screened through Independent sample t-test or Mann–Whitney U test. Variables with significant differences (p

Abstract Background Pregnancy in acromegaly is uncommon and still in debate for fear of tumor progression or potential threat to both mother and fetus’s health. Besides, the data for pregnancy complications in uncontrolled acromegaly is limited. Thus, the objective of this study was to summarize pregnancy safety and disease courses after pregnancy in acromegalic patients and review their clinical characteristics based on disease activity in the literature. Methods An evaluation of eight acromegalic women from Peking Union Medical College Hospital (PUMCH) with 11 pregnancies was conducted. We also summarized a literature review of 82 disease-active pregnancies and 63 disease-controlled pregnancies with acromegaly. A second analysis was conducted to compare pregnancy courses and outcomes in different disease activities. Results Before pregnancy, all patients had macroadenomas and underwent pituitary surgery. Pregnancy occurred at a median of 6 years (4–10) after the diagnosis of acromegaly. Assisted reproductive therapy was needed in 42.9% of participants. No cases had a premature birth or congenital malformations. Biochemical control was achieved in 50% of females before pregnancy and 75% at the last follow-up after delivery. Data analysis showed no differences in the prevalence of gestational diabetes mellitus (GDM) or pregnancy-induced hypertension (PIH) between acromegaly-active or acromegaly-controlled groups. The GDM prevalence in patients diagnosed during pregnancy (33.3%) was higher than that in patients diagnosed before pregnancy (4.8%) (p = 0.001). Conclusion Pregnancy without biochemical control in acromegaly and receiving medical treatment during pregnancy are not rare and generally safe for the fetus. There could be a higher prevalence of PIH in acromegalic pregnancies. The treatment of acromegaly and related complications can be managed with regular follow-up after pregnancy.

To further understand the characteristics of clay and sand production (hereafter collectively referred to as sand production) and to provide optimization designs of sand control schemes are critical for gas production from clayey silt natural gas hydrate reservoirs in the South China Sea. Thus, gas-water-sand production behavoirs and coupling reservoir subsidence characteristics before, during, and after hydrate dissociation of the clayey silt hydrate reservoirs with different clay contents (5%, 10%, 15%, 20%, 25%, and 30%) have been studied through a self-developed experimental system. The results show that with the increase of clay content, the total mass of sand production first increases and then decreases, and it reaches maximum when the clayey content is 20%. The sand production is the lowest before hydrate dissociation and increases significantly during hydrate dissociation, which mainly occurs in the high-speed gas and water production stage at the beginning of hydrate dissociation. After hydrate dissociation, the sand production decreases significantly. During the whole depressurization process, the clay and free sand particles generally move to the sand outlet due to the fluid driving force and overlying stress extrusion. However, for conditions of high clay contents, those particles fail to pass through the sand control screen and gradually accumulate and block the screen by forming a mud cake, which greatly reduce the permeability of the screen and limite sand production as well as gas and water production. Our research lays a foundation for sand production prediction and sand control scheme selection during gas recovery from clayey silty hydrate reservoirs that greatly need to consider a balance between sand control and gas productivity.

ObjectiveTo summarize the clinical characteristics of 4 male prolactinoma patients with severe obesity.MethodsThe clinical data of all the patients were retrospectively analyzed.ResultsAll the patients visited our hospital for severe obesity at the age of 16-30 years old with their body mass index (BMI) of 37.9-55.9 kg/m2. All the patients were obese since childhood, even at birth. Hyperprolactinemia (72.3-273.0 ng/ml) was found during the etiological screening of obesity and MRI revealed pituitary adenomas. Additionally, all of them had multiple obesity related complications, such as hyperinsulinemia and dyslipidemia. Treatment of dopamine agonists (DAs) effectively normalized their prolactin level and the pituitary MRI reexamination after 6 months of DAs treatment showed the shrinkage of the pituitary adenomas in 3 patients. Their weight also decreased in different degrees (2.70~19.03% lower than the baseline) with improved metabolic profiles.ConclusionSerum prolactin level should be screened in obese patients, especially those with severe obesity.

ObjectiveThe value of DWI and 18F-FDG PET/CT in evaluating the expression of Ki-67 and GPC-3 in HCC was compared.Materials and methodsNinety-four patients with primary HCC confirmed by pathology were retrospectively divided into high- and low-Ki-67-expression groups and positive- and negative- GPC-3 groups. The ADC and SUVmax values of the lesions in both groups were measured. ROC curves were used to evaluate the identification efficiency of parameters with significant differences for each group of lesions, and AUCwas calculated. The combined ADC and SUVmax values were analyzed by binary logistic regression. The Delong test was used to compare the AUC values of the combined and single parameters. Pearson (in line with normal distribution) or Spearman (in line with abnormal distribution) correlation analysis was used to analyze the correlation.ResultsThe ADC value of the high-Ki-67-expression group was lower than that of the low-Ki-67-expression group (P

Widespread applications of 5G technology have prompted the outsourcing of computation dominated by the Internet of Things (IoT) cloud to improve transmission efficiency, which has created a novel paradigm for improving the speed of common connected objects in IoT. However, although it makes it easier for ubiquitous resource-constrained equipment that outsources computing tasks to achieve high-speed transmission services, security concerns, such as a lack of reliability and collusion attacks, still exist in the outsourcing computation. In this paper, we propose a reliable, anti-collusion outsourcing computation and verification protocol, which uses distributed storage solutions in response to the issue of centralized storage, leverages homomorphic encryption to deal with outsourcing computation and ensures data privacy. Moreover, we embed outsourcing computation results and a novel polynomial factorization algorithm into the smart contract of Ethereum, which not only enables the verification of the outsourcing result without a trusted third party but also resists collusion attacks. The results of the theoretical analysis and experimental performance evaluation demonstrate that the proposed protocol is secure, reliable, and more effective compared with state-of-the-art approaches.

Outsourcing computation enables a computationally weak client to outsource the computation of a function f to a more powerful but untrusted server. The traditional outsourcing computation model forbids communication between players, but it has little effect. Based on the game theory, this paper establishes an outsourcing computation model which is more in line with the actual scene. Firstly, we construct a structural mapping relationship between security outsourcing computation and the optimization problem. Secondly, by designing the individual potential function and the global potential function, the individual goal is consistent with the global goal to ensure the correctness of the calculation results. Finally, in the information exchange environment between calculators, we construct a Zero-determinant strategy to ensure that the calculator chooses the strategy according to the predetermined target.

Abstract Therapeutic options are limited for severe lung injury and disease as the spontaneous regeneration of functional alveolar is terminated owing to the weakness of the inherent stem cells and the dyscrasia of the niche. Umbilical cord mesenchymal‐derived stem cells (UC‐MSCs) have been applied to clinical trials to promote lung repair through stem cell niche restruction. However, the application of UC‐MSCs is hampered by the effectiveness of cell transplantation with few cells homing to the injury sites and poor retention, survival, and proliferation in vivo. In this study, we constructed an artificial three‐dimensional (3D) biomimetic scaffold‐based MSCs implant to establish a beneficial regeneration niche for endogenous stem cells in situ lung regeneration. The therapeutic potential of 3D biomimetic scaffold‐based MSCs implants was evaluated by 3D culture in vitro. And RNA sequencing (RNA‐Seq) was mapped to explore the gene expression involved in the niche improvement. Next, a model of partial lung resection was established in rats, and the implants were implanted into the operative region. Effects of the implants on rat resected lung injury repair were detected. The results revealed that UC‐MSCs loaded on biomimetic scaffolds exerted strong paracrine effects and some UC‐MSCs migrated to the lung from scaffolds and had long‐term retention to suppress inflammation and fibrosis in residual lungs and promoted vascular endothelial cells and alveolar type II epithelial cells to enter the scaffolds. Then, under the guidance of the ECM‐mimicking structures of scaffolds and the stimulation of the remaining UC‐MSCs, vascular and alveolar‐like structures were formed in the scaffold region. Moreover, the general morphology of the operative lung was also restored. Taken together, the artificial 3D biomimetic scaffold‐based MSCs implants induce in situ lung regeneration and recovery after lung destruction, providing a promising direction for tissue engineering and stem cell strategies in lung regeneration.

Abstract Background Adaptive thermogenesis by brown adipose tissue (BAT) is important to the maintenance of temperature in newborn mammals. Cold exposure activates gene expression and lipid metabolism to provide energy for BAT thermogenesis. However, knowledge of BAT metabolism in large animals after cold exposure is still limited. Results In this study, we found that cold exposure induced expression of BAT thermogenesis genes and increased the protein levels of UCP1 and PGC1α. Pathway analysis showed that cold exposure activated BAT metabolism, which involved in cGMP-PKG, TCA cycle, fatty acid elongation, and degradation pathways. These were accompanied by decreased triglyceride (TG) content and increased phosphatidylcholine (PC) and phosphatidylethanolamine (PE) content in BAT. Conclusion These results demonstrate that cold exposure induces metabolites involved in glycerolipids and glycerophospholipids metabolism in BAT. The present study provides evidence for lipid composition associated with adaptive thermogenesis in goat BAT and metabolism pathways regulated by cold exposure.

Abstract Background The discovery of critical biomarkers is significant for clinical diagnosis, drug research and development. Researchers usually obtain biomarkers from microarray data, which comes from the dimensional curse. Feature selection in machine learning is usually used to solve this problem. However, most methods do not fully consider feature dependence, especially the real pathway relationship of genes. Results Experimental results show that the proposed method is superior to classical algorithms and advanced methods in feature number and accuracy, and the selected features have more significance. Method This paper proposes a feature selection method based on a graph neural network. The proposed method uses the actual dependencies between features and the Pearson correlation coefficient to construct graph-structured data. The information dissemination and aggregation operations based on graph neural network are applied to fuse node information on graph structured data. The redundant features are clustered by the spectral clustering method. Then, the feature ranking aggregation model using eight feature evaluation methods acts on each clustering sub-cluster for different feature selection. Conclusion The proposed method can effectively remove redundant features. The algorithm’s output has high stability and classification accuracy, which can potentially select potential biomarkers.

Abstract Sand production is a crucial geotechnical issue for safe and efficient gas recovery from natural gas hydrate (NGH) reservoirs. Although the same gas production method of depressurization was chosen for the production trials in the Nankai Trough and the Northern South China Sea, their sand production behaviors differed greatly due to the skeleton diversity of sand in the Nankai Trough and clayey‐silt in the Northern South China Sea, which resulted in different sand control and sand production characteristics. In this study, we conducted experiments to compare sediment responses and sand production behaviors from these two typical gas hydrate‐bearing sediments (GHBSs) before, during, and after hydrate dissociation under depressurization. The results reveal the fluid and sand production rates in both GHBSs are relatively low before and after hydrate dissociation. However, the sand production rate in sandy GHBS keeps stable at a relatively high value during the whole hydrate dissociation period, accompanied by a high fluid production rate and continuous sample subsidence. In contrast, the fluid and sand production rates are proved to be high only at the early stages of hydrate dissociation in clayey‐silty GHBS with sand production decreasing obviously afterward, and the sample subsidence rate exponentially decay until the ultimate subsidence is reached. After experiments, two kinds of particle plugging phenomena, sand bridge and mud cake, are found to form outside sand screens in sandy and clayey‐silty GHBSs, respectively. Differences in permeability, particle migration, and plugging characteristics are thought to be the main inducement of the variability in sand production behaviors in different GHBS types. These findings indicate that sand‐production control strategies should obey geological engineering integration and differ according to the GHBS type. Specifically, we should concern sand production risk in sandy GHBS during and after hydrate dissociation, whereas more attention should be paid to the early stages of hydrate dissociation in clayey‐silty GHBS.

Abstract Background The pigmentation phenotype diversity is rich in domestic goats, and identification of the genetic loci affecting coat color in goats has long been of interest. Via the detections of selection signatures, a duplication upstream ASIP was previously reported to be a variant affecting the Swiss markings depigmentation phenotype in goats. Results We conducted a genome-wide association study using whole-genome sequencing (WGS) data to identify the genetic loci and causal variants affecting the pigmentation phenotype in 65 Jintang black (JT) goats (i.e., 48 solid black vs. 17 non-classic Swiss markings). Although a single association peak harboring the ASIP gene at 52,619,845–72,176,538 bp on chromosome 13 was obtained using a linear mixed model approach, all the SNPs and indels in this region were excluded as causal variants for the pigmentation phenotype. We then found that all 17 individuals with non-classic Swiss markings carried a 13,420-bp duplication (CHI13:63,129,198–63,142,617 bp) nearly 101 kb upstream of ASIP, and this variant was strongly associated (P = 1.48 × 10− 12) with the coat color in the 65 JT goats. The copy numbers obtained from the WGS data also showed that the duplication was present in all 53 goats from three European breeds with Swiss markings and absent in 45 of 51 non-Swiss markings goats from four other breeds and 21 Bezoars, which was further validated in 314 samples from seven populations based on PCR amplification. The copy numbers of the duplication vary in different goat breeds with Swiss markings, indicating a threshold effect instead of a dose-response effect at the molecular level. Furthermore, breakpoint flanking repeat analysis revealed that the duplication was likely to be a result of the Bov-B-mediated nonallelic homologous recombination. Conclusion We confirmed that a genomic region harboring the ASIP gene is a major locus affecting the coat color phenotype of Swiss markings in goats. Although the molecular genetic mechanisms remain unsolved, the 13,420-bp duplication upstream of ASIP is a necessary but not sufficient condition for this phenotype in goats. Moreover, the variations in the copy number of the duplication across different goat breeds do not lead to phenotypic heterogeneity.

In this work, liquid-phase catalytic oxidation of toluene was carried out under solvent-free conditions, and highly selective synthesis of benzaldehyde (BAL) and benzyl alcohol (BOL) and benzoic acid (BAC) in the presence of Mn@ZIF-8 calcined material as catalyst with oxygen molecules. As a heterogeneous catalyst, the zeolitic imidazolate framework Mn@ZIF-8 derived material exhibited reasonable substrate-product selectivity (70.3% of selectivity to BAL and BOL, 95.1 % of selectivity to BAL, BOL and BAC) and conversion (6.5%) under optimum reaction conditions. The catalysts were characterized by BET-specific surface area determination, XRD, XPS, FT-IR, TG-DTG and SEM-EDS-Mapping. The results demonstrated that the catalytic capacity of the catalysts was enhanced by the good dispersion of amorphous Mn species in ZIF-8 derivatives and high specific surface area. The possible reaction pathway for the catalytic oxidation of toluene was also suggested. Maybe this method employing Mn@ZIF-8 as efficient catalyst affords a new and environmentally friendly route for the synthesis of BOL and BAL from the selective oxidation of toluene.

Tibetan goats, Taihang goats, Jining grey goats, and Meigu goats are the representative indigenous goats in China, found in Qinghai-Tibet Plateau, Western pastoral area, Northern and Southern agricultural regions. Very few studies have conducted a comprehensive analysis of the genomic diversity and selection of these breeds. We genotyped 96 unrelated individuals, using goat 53 K Illumina BeadChip array, of the following goat breeds: Tibetan (TG), Taihang (THG), Jining grey (JGG), and Meigu (MGG). A total of 45 951 single nucleotide polymorphisms were filtered to estimate the genetic diversity and selection signatures. All breeds had a high proportion (over 95%) of polymorphic loci. The observed and excepted heterozygosity ranged from 0.338 (MGG) to 0.402 (JGG) and 0.339 (MGG) to 0.395 (JGG), respectively. Clustering analysis displayed a genetically distinct lineage for each breed, and their Fst were greater than 0.25, indicating that they had a higher genetic differentiation between groups. Furthermore, effective population size reduced in all four populations, indicating a loss of genetic diversity. In addition, runs of homozygosity were mainly distributed in 5–10 Mb. Lastly, we identified signature genes, which were closely related to high-altitude adaptation (ADIRF) and prolificity (CNTROB, SMC3, and PTEN). This study provides a valuable resource for future studies on genome-wide perspectives on the diversity and selection signatures of Chinese indigenous goats.

Abstract Background Recently, side effects from Dopamine Receptor Agonist Drugs (DAs) in treating pituitary prolactinoma have raised widespread concern. This study explores the incidence and influencing factors of DAs-related side effects in Chinese prolactinoma patients. Methods A cross-sectional study was conducted. 51 prolactinoma patients treated with DAs, 12 prolactinoma or pituitary microadenoma patients without DAs treatment, and 33 healthy controls were included. The Barratt impulsivity scale-11, Patient Health Questionnaire 9, and the ICD screening questionnaire were all used to evaluate the psychological and physical side effects of DAs. Clinical data of all subjects were collected from their electronic medical records. Results The incidence of ICDs in the treated group, the untreated group, and control group was 9.8% (5/51), 16.7% (2/12), and 9.1% (3/33), respectively. In the treated group in particular, there were 1 patient (2%, 1/51), 2 patients (3.9%, 2/51), and 2 patients (3.9%, 2/51) with positive screening for punding, compulsive shopping, and hypersexuality, respectively. In terms of depression, the incidence of "minimal", "mild" and "moderate" depression in the treated group was 62.8% (32/51), 25.5% (13/51), and 5.9% (3/51), respectively. The incidence of physical symptoms was 51.0% (26/51) in the treated group and gastrointestinal symptoms were the most common symptoms (33.3%, 17/51). In addition, we found that the various parameters of DAs treatment had no association with the occurrence of physical symptoms or ICDs (all P > 0.05). Conclusions Chinese prolactinoma patients treated with DAs had a lower incidence of ICDs (9.8%), while gastrointestinal symptoms were common. In this way, more attention should be paid to side effects, especially physical symptoms, in Chinese prolactinoma patients with DAs therapy during follow-up regardless of dose.

Abstract Background MicroRNAs (miRNAs) are a family of short non-coding RNA molecules and play important roles in various biological processes. However, knowledge of the expression profiles and function of miRNAs on the regulation of brown adipose tissue (BAT) thermogenesis remains largely unknown. Results In this study, we found that brown adipose tissue (BAT) existed within the perirenal fat at 1 day after birth (D1) and transferred into white adipose tissue (WAT) at 30 days after birth (D30) by UCP1 protein expression and immunohistochemistry analysis. After that, we performed RNA sequencing on six libraries of goat BAT and WAT. A total of 238 known miRNAs and 1834 goat novel miRNAs were identified. Moreover, 395 differentially expressed miRNAs including 167 up-regulated and 228 down-regulated miRNAs were obtained in BAT. For the known BAT enriched miRNA, 30 miRNAs were enriched in goat BAT but not in mouse BAT. In addition, miR-433 was enriched in goat BAT but not in mouse BAT. Gain- and loss-of-function experiments reveal that miR-433 reduced the lipid accumulation of brown adipocytes and decreased the expression of BAT marker and mitochondrial related genes. However, miR-433 had no effect on lipid accumulation and thermogenesis in white adipocytes. In addition, miR-433 inhibited the expression of MAPK8 by targeting to the 3’UTR of MAPK8 gene. These data demonstrate that miR-433 acts as a negative regulator in controlling brown adipocytes differentiation and thermogenesis. Conclusion The present study provides a detailed miRNAs expression landscape in BAT and WAT. Furthermore, we found that miR-433, which was highly expressed on BAT had a negative regulatory function on the thermogenesis and adipogenesis in goat brown adipocytes. This study provides evidence for understanding the role of miRNAs in regulating BAT thermogenesis and energy expenditure in goats.

Vascular endothelial growth factor A (VEGFA) plays important roles in angiogenesis, inflammatory response as well as energy metabolism in mammals. However, its effect on glycolipid metabolism in fish has not been reported. In this study, we cloned and characterized the vegfa gene of Schizothorax prenanti (S. prenanti). vegfa expression was significantly higher in liver and muscle than that in other tissues. Then, the VEGFA recombinant protein was expressed in Escherichia coli and obtained after purification. VEGFA i.p. injection significantly increased the serum glucose and TG content compared with the control group. Moreover, VEGFA protein aggravated the glycogen and lipid deposition in the liver of S. prenanti. In addition, we found that VEGFA treatment increased hepatocyte glycogen and lipid droplet content and increased the levels of pAMPKα (T172). Furthermore, AMPKα inhibition attenuated the ability of VEGFA to induce TG and glycogen accumulation. These results demonstrate that VEGFA regulates hepatic lipid and glycogen metabolism through AMPKα in S. prenanti, which may contribute to a better understanding of VEGFA functions in the glycolipid metabolism of fish.

The development of mammalian skeletal muscle is a highly complex process involving multiple molecular interactions. As a prevalent RNA modification, N6-methyladenosine (m6A) regulates the expression of target genes to affect mammalian development. Nevertheless, it remains unclear how m6A participates in the development of goat muscle. In this study, methyltransferase 3 (METTL3) was significantly enriched in goat longissimus dorsi (LD) tissue. In addition, the global m6A modification level and differentiation of skeletal muscle satellite cells (MuSCs) were regulated by METTL3. By performing mRNA-seq analysis, 8050 candidate genes exhibited significant changes in expression level after the knockdown of METTL3 in MuSCs. Additionally, methylated RNA immunoprecipitation sequencing (MeRIP-seq) illustrated that myocyte enhancer factor 2c (MEF2C) mRNA contained m6A modification. Further experiments demonstrated that METTL3 enhanced the differentiation of MuSCs by upregulating m6A levels and expression of MEF2C. Moreover, the m6A reader YTH N6-methyladenosine RNA binding protein C1 (YTHDC1) was bound and stabilized to MEF2C mRNA. The present study reveals that METTL3 enhances myogenic differentiation in MuSCs by regulating MEF2C and provides evidence of a post-transcriptional mechanism in the development of goat skeletal muscle.

Cold exposure influences liver metabolism, thereby affecting energy homeostasis. However, the gene regulatory network of the liver after cold exposure remains poorly understood. In this study, we found that 24 h cold exposure (COLD, 6 °C) increased plasma glucose (GLU) levels, while reducing plasma non-esterified fatty acid (NEFA) and triglyceride (TG) levels compared to the room temperature (RT, 25 °C) group. Cold exposure increased hepatic glycogen content and decreased hepatic lipid content in the livers of newborn goats. We conducted RNA-seq analysis on the livers of newborn goats in both the RT and cold exposure groups. A total of 1600 genes were identified as differentially expressed genes (DEGs), of which 555 genes were up-regulated and 1045 genes were down-regulated in the cold exposure group compared with the RT group. Cold exposure increased the expression of genes involved in glycolysis, glycogen synthesis, and fatty acid degradation pathways. These results can provide a reference for hepatic lipid and glycogen metabolism in newborn goats after cold exposure.

Abstract Background The increasing numbers of women in the workforce is an inevitable trend in China. More and more employed women stop breastfeeding because of working stressors. Many mothers, however, overcome the challenges and insist on breastfeeding after returning to work. Their individual experience of breastfeeding may provide a new insight to promote and support breastfeeding on employed mothers. This study sought to understand mothers’ experience with insisting on breastfeeding after returning to work based on Kumpfer’s Resilience Framework in Chinese context. Methods This qualitative study was designed with semi-structured interviews. Purposive sampling and snowball sampling were employed to recruit 13 full-time working mothers with a stable job in the public sector who continued to breastfeed for 1 month or longer after returning to work in Haikou, Hainan Province, China. Interviews were conducted from January to March 2020 to capture participants’ experiences of breastfeed after returning to work. Grounded theory and Kumpfer’s Resilience Framework were used to analyze data via a systematic and iterative process. Results Employed mothers built resilience while continuing to breastfeed after returning to work. The core concept was "dynamic interaction". Other categories were the background and explanation of this phenomenon. For working mothers who continued to breastfeed, resilience involved "dynamic interaction", which started from "experiencing stressors" and "obtaining support", two environmental factors interacted with the individual to "build resilience qualities", which interact with environment led to “behavioral resilience”. And then the ongoing dynamic interaction between behavioral resilience and environment ultimately led to three different "weaning processes", including natural weaning, active weaning, and forced weaning. Conclusions This study identified the framework of resilience in mothers who were in the adversity of breastfeeding after returning to work based on Kumpfer’s Resilience Framework. It provided a new insight into the resilience of employed mothers around the world to continue breastfeeding and showed the different culture of breastfeeding on employed mothers.

Abstract Background The differential diagnosis of IgG4-related hypophysitis and other inflammatory diseases or tumors involving sellar region is challenging even after sellar biopsy. Sellar germinoma is usually infiltrated by lymphocytes or plasma cells, and may be confused with hypophysitis. Case presentation A 36-year-old man with diabetes insipidus, elevated serum IgG4 level (336 mg/dl), and sellar mass was suspected to have IgG4-related hypophysitis, and no other lesion of IgG4-related disease was detected. After treated by prednisone and mycophenolate mofetil, the serum IgG4 decreased to 214 mg/dl. However, after withdrawal of the drugs, the IgG4 level increased to 308 mg/dl. Endocrine assessments revealed panhypopituitarism, and the sellar mass enlarged. Transsphenoidal sellar exploration and biopsy was conducted. Pathological examination showed that the lesion was germinoma with lymphocytes and plasma cells infiltration, and IgG4-staining was positive (70/HPF, IgG4/IgG ratio = 10%). The patient was then treated by cisplatin and etoposide. After four cycles of chemotherapy, the serum IgG4 was 201 mg/dl, and the sellar mass was invisible. Conclusion Sellar germinoma can mimic the clinical characteristics of IgG4-related hypophysitis. Poor response to glucocorticoids can be used as an exclusion criterion in the clinical diagnosis of IgG4-related hypophysitis.

Abstract Background The comparatively low 25 hydroxyvitamin D [25(OH)D] levels have been reported in patients with metabolic syndrome (MetS). Herein we investigated the cross-sectional and longitudinal relationships between serum 25(OH)D levels and MetS risk profile in northern middle-aged Chinese subjects without vitamin D supplementation. Methods A cohort of 211 participants including 151 MetS patients and 60 controls at 20–69 years of age were enrolled from suburban Beijing, China. The recruited MetS patients were subjected to diet and exercise counselling for 1-year. All subjects at baseline and MetS patients after intervention underwent clinical evaluations. Results Serum 25(OH)D levels were significantly decreased in MetS patients. 25(OH)D levels were inversely related to MetS score, fasting blood glucose (FBG) and triglyceride-glucose index (TyG) after adjusting for cofounders (all P

Phosphorus (P) is one of the essential macronutrients for plant growth and development, and it is an integral part of the major organic components, including nucleic acids, proteins and phospholipids. Although total P is abundant in most soils, a large amount of P is not easily absorbed by plants. Inorganic phosphate (Pi) is the plant-available P, which is generally immobile and of low availability in soils. Hence, Pi starvation is a major constraint limiting plant growth and productivity. Enhancing plant P efficiency can be achieved by improving P acquisition efficiency (PAE) through modification of morpho-physiological and biochemical alteration in root traits that enable greater acquisition of external Pi from soils. Major advances have been made to dissect the mechanisms underlying plant adaptation to P deficiency, especially for legumes, which are considered important dietary sources for humans and livestock. This review aims to describe how legume root growth responds to Pi starvation, such as changes in the growth of primary root, lateral roots, root hairs and cluster roots. In particular, it summarizes the various strategies of legumes to confront P deficiency by regulating root traits that contribute towards improving PAE. Within these complex responses, a large number of Pi starvation-induced (PSI) genes and regulators involved in the developmental and biochemical alteration of root traits are highlighted. The involvement of key functional genes and regulators in remodeling root traits provides new opportunities for developing legume varieties with maximum PAE needed for regenerative agriculture.

Countermeasures in weightlessness are a predominant technique for long-term residency in space. Head-down bed rest (HDBR) has long been used to simulate the physiological effects of spaceflight and test the efficacy of countermeasures. In 2019, the Astronaut Center of China (ACC) has held a 90-d HDBR on the effects of exercises’ intervention. Thirty-six subjects were recruited and randomized into 5 intervention groups: (a) control, (b) aerobic exercises, (c) resistance exercises, (d) concurrent aerobic and lower load resistance exercises, and (e) concurrent aerobic and high-load resistance exercises. Moreover, exercise interventions were performed in supine or 6° head-down tilt. They were provided with plain medical, psychological, and nutritional supports during the experiment. In addition, cardiovascular and pulmonary functions, muscle strength, bone density, and neuro–immune–endocrine functions were assessed over time. Subjects were monitored by clinical evaluations, psychological assessments, and nutritional status evaluations. All subjects spent 138 d in the bed rest study laboratory and received 2 follow-up tests per 3 months in the home recovery period. It was found that exercises in the 4 groups were effective interventions for aerobic capacity compared with control. The resistance exercises or concurrent aerobic and high-load resistance exercises improved isometric maximal voluntary contraction. However, the protection against bone loss still needs further exploration. Appropriate psychosocial and nutrition support techniques are worth to be reinforced.

Metal-organic framework materials (MOFs) have been widely used in food contamination adsorption and detection due to their large specific surface area, specific pore structure and flexible post-modification. MOFs with specific pore size can be targeted for selective adsorption of some contaminants and can be used as pretreatment and pre-concentration steps to purify samples and enrich target analytes for food contamination detection to improve the detection efficiency. In addition, MOFs, as a new functional material, play an important role in developing new rapid detection methods that are simple, portable, inexpensive and with high sensitivity and accuracy. The aim of this paper is to summarize the latest and insightful research results on MOFs for the adsorption and detection of food contaminants. By summarizing Zn-based, Cu-based and Zr-based MOFs with low cost, easily available raw materials and convenient synthesis conditions, we describe their principles and discuss their applications in chemical and biological contaminant adsorption and sensing detection in terms of stability, adsorption capacity and sensitivity. Finally, we present the limitations and challenges of MOFs in food detection, hoping to provide some ideas for future development.

IntroductionPediatric growth hormone deficiency (GHD) is a disease resulting from impaired growth hormone/insulin-like growth factor-1 (IGF-1) axis but the effects of GHD on children’s cognitive function, brain structure and brain function were not yet fully illustrated.MethodsFull Wechsler Intelligence Scales for Children, structural imaging, diffusion tensor imaging, and resting-state functional magnetic resonance imaging were assessed in 11 children with GHD and 10 matched healthy controls.Results(1) The GHD group showed moderate cognitive impairment, and a positive correlation existed between IGF-1 levels and cognitive indices. (2) Mean diffusivity was significantly increased in both corticospinal tracts in GHD group. (3) There were significant positive correlations between IGF-1 levels and volume metrics of left thalamus, left pallidum and right putamen but a negative correlation between IGF-1 levels and cortical thickness of the occipital lobe. And IGF-1 levels negatively correlated with fractional anisotropy in the superior longitudinal fasciculus and right corticospinal tract. (4) Regional homogeneity (ReHo) in the left hippocampus/parahippocampal gyrus was negatively correlated with IGF-1 levels; the amplitude of low-frequency fluctuation (ALFF) and ReHo in the paracentral lobe, postcentral gyrus and precentral gyrus were also negatively correlated with IGF-1 levels, in which region ALFF fully mediates the effect of IGF-1 on working memory index.ConclusionMultiple subcortical, cortical structures, and regional neural activities might be influenced by serum IGF-1 levels. Thereinto, ALFF in the paracentral lobe, postcentral gyrus and precentral gyrus fully mediates the effect of IGF-1 on the working memory index.

Abstract Background We aimed to investigate the clinical characteristics and islet β-cell function in patients with Klinefelter syndrome (KS) and hyperglycemia. Methods This is a retrospective study. In total, 22 patients diagnosed with KS were identified from the electronic medical record system, including 9 patients with hyperglycemia (total patients with hyperglycemia, THG-KS group) and 5 hyperglycemic KS patients with oral glucose tolerance test (OGTT) results (HG-KS group). An additional 5 subjects with hyperglycemia and 5 normal glucose tolerance (NGT) subjects matched based on body mass index were included as the HG group and NGT group, respectively. Data from clinical and laboratory examinations were collected. We further performed a literature review of KS and hyperglycemia. Results We found that KS patients developed abnormal glucose metabolism earlier in life than those without KS, and the median age was 17 years, ranging from 10 years to 19 years. Six of 17 (35.3%) patients were diagnosed with diabetes mellitus and 3 of 17 (17.6%) patients were diagnosed with prediabetes. Among 10 patients with both fasting blood glucose and insulin results recorded, there were 8 out of 17 (47.1%) KS patients had insulin resistance. The prevalence of hypertension and dyslipidemia was higher in patients with hyperglycemia and KS than in patients with NGT KS. Compared with the HG group, insulin sensitivity levels were lower in HG-KS group, whereas homeostasis model assessment of β-cell function levels (p = 0.047) were significantly, indicating higher insulin secretion levels in the HG-KS group. Conclusions KS patients develop hyperglycemia earlier in life than those without KS and show lower insulin sensitivity and higher insulin secretion. These patients also have a higher prevalence of other metabolic diseases and may have different frequencies of developing KS-related symptoms.

Abstract In bioinformatics, the rapid development of gene sequencing technology has produced an increasing amount of microarray data. This type of data shares the typical characteristics of small sample size and high feature dimensions. Searching for biomarkers from microarray data, which expression features of various diseases, is essential for the disease classification. feature selection has therefore became fundemental for the analysis of microarray data, which designs to remove irrelevant and redundant features. There are a large number of redundant features and irrelevant features in microarray data, which severely degrade the classification effectiveness. We propose an innovative feature selection method with the goal of obtaining feature dependencies from a priori knowledge and removing redundant features using spectral clustering. In this paper, the graph structure is firstly constructed by using the gene interaction network as a priori knowledge, and then a link prediction method based on graph neural network is proposed to enhance the graph structure data. Finally, a feature selection method based on spectral clustering is proposed to determine biomarkers. The classification accuracy on DLBCL and Prostate can be improved by 10.90% and 16.22% compared to traditional methods. Link prediction provides an average classification accuracy improvement of 1.96% and 1.31%, and is up to 16.98% higher than the published method. The results show that the proposed method can have full use of a priori knowledge to effectively select disease prediction biomarkers with high classification accuracy.

Abstract Background Finding significant genes or proteins from gene chip data for disease diagnosis and drug development is an important task. However, the challenge comes from the curse of the data dimension. It is of great significance to use machine learning methods to find important features from the data and build an accurate classification model. Results The proposed method has proved superior to the published advanced hybrid feature selection method and traditional feature selection method on different public microarray data sets. In addition, the biomarkers selected using our method show a match to those provided by the cooperative hospital in a set of clinical cleft lip and palate data. Method In this paper, a feature selection algorithm ILRC based on clustering and improved L1 regularization is proposed. The features are firstly clustered, and the redundant features in the sub-clusters are deleted. Then all the remaining features are iteratively evaluated using ILR. The final result is given according to the cumulative weight reordering. Conclusion The proposed method can effectively remove redundant features. The algorithm’s output has high stability and classification accuracy, which can potentially select potential biomarkers.

Abstract Background There is a long-term interest in investigating the genetic basis of the horned/polled phenotype in domestic goats. Here, we report a genome-wide association study (GWAS) to detect the genetic loci affecting the polled phenotype in goats. Results We obtained a total of 13,980,209 biallelic SNPs, using the genotyping-by-sequencing data from 45 Jintang Black (JT) goats, which included 32 female and nine male goats, and four individuals with the polled intersex syndrome (PIS). Using a mixed-model based GWAS, we identified two association signals, which were located at 150,334,857–150,817,260 bp (P = 5.15 × 10− 119) and 128,286,704–131,306,537 bp (P = 2.74 × 10− 15) on chromosome 1. The genotype distributions of the 14 most significantly associated SNPs were completely correlated with horn status in goats, based on the whole-genome sequencing (WGS) data from JT and two other Chinese horned breeds. However, variant annotation suggested that none of the detected SNPs within the associated regions were plausible causal mutations. Via additional read-depth analyses and visual inspections of WGS data, we found a 10.1-kb deletion (CHI1:g. 129424781_129434939del) and a 480-kb duplication (CHI1:150,334,286–150,818,098 bp) encompassing two genes KCNJ15 and ERG in the associated regions of polled and PIS-affected goats. Notably, the 10.1-kb deletion also served as the insertion site for the 480-kb duplication, as validated by PCR and Sanger sequencing. Our WGS genotyping showed that all horned goats were homozygous for the reference alleles without either the structural variants (SVs), whereas the PIS-affected goats were homozygous for both the SVs. We also demonstrated that horned, polled, and PIS-affected individuals among 333 goats from JT and three other Chinese horned breeds can be accurately classified via PCR amplification and agarose gel electrophoresis of two fragments in both SVs. Conclusion Our results revealed that two genomic regions on chromosome 1 are major loci affecting the polled phenotypes in goats. We provided a diagnostic PCR to accurately classify horned, polled, and PIS-affected goats, which will enable a reliable genetic test for the early-in-life prediction of horn status in goats.

The incidence of diarrhea in lambs is frequent in large-scale sheep farms, which greatly impacts the growth and health of lambs. The aim of this study was to assess the changes in serum biochemical and immunological parameters and gut microbiome composition in suckling lambs suffering from diarrhea or not, reared on an intensive commercial farm. We found a reduced diversity of intestinal bacteria in suckling lambs suffering from diarrhea. Firmicutes and Bacteroidetes were the dominant flora in both groups of lambs, while the Bacteroidetes decreased in diarrheic lambs, no changes were reported in Firmicutes. Compared with healthy lambs, the proportion of aerobic bacteria, facultative anaerobic bacteria, and stress tolerant bacteria increased in lambs suffering from diarrhea, while that of anaerobic bacteria and potentially pathogenic bacteria decreased slightly. In addition, the contents of total cholesterol, immunoglobulins (Ig) G, and IgM in the serum of lambs suffering from diarrhea were lower than those of healthy lambs. This study explored the association between diarrhea occurrence, intestinal microbial community structure, and metabolic and immunological status in Hu lambs.