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Abstract Metabolic dysfunction associated fatty liver disease (MAFLD) is a common cause of liver disease in children and adolescents. The relationship between insulin resistance (IR) and MAFLD in children with short stature remains largely unknown. The present study was to investigate the relationship between the triglyceride–glucose (TyG) index and alanine aminotransferase (ALT) levels in children with short stature. A total of 1754 children with short stature were enrolled. Anthropometric, biochemical and hormonal indexes were collected through physical measurement examinations and laboratory tests. A nonlinear association was found between the TyG index and ALT. The inflection point of the curve was at a TyG index of 8.24. In multivariate piecewise linear regression, only when the TyG index was greater than 8.24 was there a significant positive association between the TyG index and ALT (β 5.75, 95% CI 3.30, 8.19; P < 0.001). However, when the TyG index was less than 8.24, there was no significant association between the TyG index and ALT (β −0.57, 95% CI −1.84, 0.71; P = 0.382). This study demonstrated a nonlinear relationship between TyG index and ALT in children with short stature. This finding suggests that a high TyG index is associated with elevated ALT in children with short stature.

Abstract Human‐wildlife interactions become increasingly common in urban areas across all continents and ecosystem types. Depending on the context, human‐wildlife interactions can be categorized as harmonious, neutrality, or in conflict and raises cultural, economic and ecological challenges in maintaining urban biodiversity. Understanding the mechanism behind the tolerance of residents to the presence of wildlife is vital to promoting a harmonious coexistence between humans and wildlife in urban environments. To advance our knowledge of this mechanism, we developed a questionnaire to survey residents in Shanghai, China about their knowledge of and attitude towards raccoon dogs (Nyctereutes procyonoides), a species whose population is increasing in urban areas. Using 281 questionnaires, we conducted structural equation modelling to examine how relational values, including familiarity with raccoon dogs, perceived benefits and risks, together with residents' trust in wildlife management authorities, interactively influence the tolerance for this species. We found that the residents' familiarity with raccoon dogs positively influenced their tolerance, both directly and indirectly through increased perceived benefits and reduced perceived risks. Furthermore, trust in wildlife management authorities contributed to higher tolerance through perceived benefits. Our results suggested that education about the relational values of raccoon dogs to the public can reduce the traditional negative connotation for this species and promote the coexistence of people and raccoon dogs in Shanghai urban environment. Based on our understanding about how raccoon dogs were culturally constructed and the willingness of residents to share landscapes with the species, we advocate that relational values play an important role in future urban biodiversity conservation planning. We also advocate for education programs that familiarize the public with raccoon dogs as well as other species, which can turn urban human‐wildlife conflicts into harmonious relationships in Shanghai and other urban areas. Read the free Plain Language Summary for this article on the Journal blog.

BackgroundSecondary osteoporosis is associated with type 2 diabetes mellitus (T2DM), and there is conflicting evidence regarding the relationship between insulin-like growth factor-1 (IGF-1) and bone mineral density (BMD) in different populations. The objective of this study was to investigate the relationship between serum IGF-1 levels and BMD in patients with T2DM.MethodA retrospective cross-sectional study was performed on a cohort of 363 patients with T2DM, comprising men aged over 50 and women who are postmenopausal. Those with no significant medical history or medication affecting BMD or IGF-1 were considered. Data analyzed included IGF-1 levels, markers of bone metabolism, and measurements of BMD. To account for age and gender variations, we calculated IGF-1 standard deviation scores (IGF-1 SDS) for further investigation.ResultsA significant increase in BMD at lumbar spine (LS), femoral neck (FN), and total hip (TH) was observed as IGF-1 SDS tertiles rose. We revealed a nonlinear correlation between IGF-1 SDS and BMD at these sites, with a common inflection point identified at an IGF-1 SDS level of -1.68. Additionally, our multivariate piecewise linear regression analysis highlighted a positive association between IGF-1 SDS and BMD at LS, FN, and TH when IGF-1 SDS exceeded the inflection point (β 0.02, 95% CI 0.01, 0.04 for LS; β 0.02, 95% CI 0.01, 0.03 for FN; β 0.02, 95% CI 0.01, 0.03 for TH). Conversely, below the inflection point, this association was not significant (β -0.04, 95% CI -0.10, 0.01 for LS; β -0.04, 95% CI -0.08, 0.01 for FN; β -0.03, 95% CI -0.08, 0.01 for TH).ConclusionThese findings reveal a nonlinear relationship between IGF-1 SDS and BMD in T2DM patients. Higher serum IGF-1 levels were connected to increased bone density only after surpassing a certain threshold.

In this study, chlorogenic acid-modified hyaluronic acid (HA-CGA) and phenylboric acid-modified ciprofloxacin (Cip-BPA) were synthesized and their structures were analyzed by 1HNMR and 13CNMR. Following, a dynamic borate and hydrogen bond crosslinked HCCB hydrogel was prepared by mixing HA-CGA and Cip-BPA solution. Its properties and gel formation mechanism were studied by means of ratio optimization, scanning electron microscopy, rheology, 11B-NMR and temperature-changing infrared spectroscopy. The basic properties and bioactivity of HCCB hydrogel were investigated by in vitro antibacterial experiment, in vitro anti-inflammatory oxidation experiment and biocompatibility test. We found that borate ester bond and hydrogen bond are important driving forces for the formation of HCCB hydrogels, and when the molar ratio of chlorogenic acid in HA-CGA and phenylboronic acid in Cip-BPA is 2:1, the properties of HCCB hydrogels formed are the best. It has excellent antibacterial properties, anti-inflammatory and antioxidant properties, good biocompatibility and pH/ROS response. The successful preparation of the gel and its excellent properties indicate that it has great potential in the treatment of some inflammation treatment.

To determine the cooperative variation laws of temperature fields in bridge concrete piles and the surrounding frozen soil during the freezing process in high-latitude, low-altitude insular permafrost regions, we utilized a practical bridge construction project within the frozen soil area of the Daxing'an Mountains, China. This served as the foundation for developing a method to remotely and dynamically monitor the temperatures of piles and soil in permafrost regions, enabling continuous, automatic monitoring of pile-soil temperature data. Employing this automatic temperature monitoring system, we collected temperature data from two 15-m-long concrete bored piles before and after freezing, and monitored the freezing process of the pile foundations in real-time. The cooperative variation laws of the pile-soil temperature field over time were summarized, and a calculation equation for the pile foundation's freezing time was established based on finite element analysis results. Monitoring and analysis reveal that under the influence of the frozen soil temperature field, the pile foundation initially freezes from the bottom up in a unidirectional manner. When the atmospheric temperature falls below 0 °C, the pile foundation freezes simultaneously from both the upper and lower directions. Post-freezing, the internal temperature of the pile body aligns with the surrounding soil temperature, with a temperature difference of less than 0.1 °C at the same depth. For similar in-place temperatures, the freezing time for a test pile with a 1.2m diameter is 1.14 times that of a 1.0m diameter test pile. The range of the hydration heat effect of cement concrete extends 1–2 times the pile diameter.

Tuberculosis is a chronic infectious disease, caused by Mycobacterium tuberculosis, that seriously endangers human health. Skeletal tuberculosis is the most common type of extrapulmonary tuberculosis and tuberculous arthritis is the second most common type of skeletal tuberculosis. We report a case series of patients with tuberculous arthritis, two of whom had no joint disease in the past and presented as monoarthritis. The final patient had a history of rheumatoid arthritis, with polyarthritis that was aggravated during treatment with glucocorticoids and immunosuppressive drugs. This series of cases can contribute to early diagnosis and treatment with appropriate infection control measures.

Abstract Introduction Recently, chloride channel CLIC‐like 1 (CLCC1) was reported to be a novel ALS‐related gene. We aimed to screen CLCC1 variants in our ALS cohort and further explore the genotype–phenotype correlation of CLCC1‐related ALS. Methods We screened rare damaging variants in CLCC1 from our cohorts of 1005 ALS patients and 1224 healthy controls with whole‐exome sequencing in Central South China. Fisher's exact test was conducted for association analysis at the entire gene level and single variant level. Results In total, four heterozygous missense variants in CLCC1 were identified from four unrelated sporadic ALS patients and predicted to be putative pathogenic by in silico tools and protein model prediction, accounting for 0.40% of all patients (4/1005). The four variants were c.A275C (p.Q92P), c.G1139A (p.R380K), c.C1244T (p.T415M), and c.G1328A (p.R443Q), respectively, which had not been reported in ALS patients previously. Three of four variants were located in exon 10. Patients harboring CLCC1 variants seemed to share a group of similar clinical features, including earlier age at onset, rapid progression, spinal onset, and vulnerable cognitive status. Statistically, we did not find CLCC1 to be associated with the risk of ALS at the entire gene level or single variant level. Conclusion Our findings further expanded the genetic and clinical spectrum of CLCC1‐related ALS and provided more genetic evidence for anion channel involvement in the pathogenesis of ALS, but further investigations are needed to verify our findings.

Highlights The well-conceived Pt–Ni3S2 heteronanocrystals with dual-monodispersed characteristics are synthesized through interfacial electronic modulation. The asymmetrical charge distribution at Pt–Ni3S2 hetero-interface results in the formation of high-valent Ni sites and negatively-charged Pt δ−. It eventually accelerates water dissociation and achieves the steady concurrent generation of value-added formate and hydrogen.

ObjectiveNutritional intervention prior to the occurrence of cachexia will significantly improve the survival rate of lung cancer patients. This study aimed to establish an ensemble learning model based on anthropometry and blood indicators without information on body weight loss to identify the risk factors of cachexia for early administration of nutritional support and for preventing the occurrence of cachexia in lung cancer patients.MethodsThis multicenter study included 4,712 lung cancer patients. The least absolute shrinkage and selection operator (LASSO) method was used to obtain the key indexes. The characteristics excluded weight loss information, and the study data were randomly divided into a training set (70%) and a test set (30%). The training set was used to select the optimal model among 18 models and verify the model performance. A total of 18 machine learning models were evaluated to predict the occurrence of cachexia, and their performance was determined using area under the curve (AUC), accuracy, precision, recall, F1 score, and Matthews correlation coefficient (MCC).ResultsAmong 4,712 patients, 1,392 (29.5%) patients were diagnosed with cachexia based on the framework of Fearon et al. A 17-variable gradient boosting classifier (GBC) model including body mass index (BMI), feeding situation, tumor stage, neutrophil-to-lymphocyte ratio (NLR), and some gastrointestinal symptoms was selected among the 18 machine learning models. The GBC model showed good performance in predicting cachexia in the training set (AUC = 0.854, accuracy = 0.819, precision = 0.771, recall = 0.574, F1 score = 0.658, MCC = 0.549, and kappa = 0.538). The abovementioned indicator values were also confirmed in the test set (AUC = 0.859, accuracy = 0.818, precision = 0.801, recall = 0.550, F1 score = 0.652, and MCC = 0.552, and kappa = 0.535). The learning curve, decision boundary, precision recall (PR) curve, the receiver operating curve (ROC), the classification report, and the confusion matrix in the test sets demonstrated good performance. The feature importance diagram showed the contribution of each feature to the model.ConclusionsThe GBC model established in this study could facilitate the identification of cancer cachexia in lung cancer patients without weight loss information, which would guide early implementation of nutritional interventions to decrease the occurrence of cachexia and improve the overall survival (OS).

Background Ovarian cancer is the most lethal gynecological malignancy, with limited treatment options after failure of standard therapies. Despite the potential of poly(ADP-ribose) polymerase inhibitors in treating DNA damage response (DDR)-deficient ovarian cancer, the development of resistance and immunosuppression limit their efficacy, necessitating alternative therapeutic strategies. Inhibitors of poly(ADP-ribose) glycohydrolase (PARG) represent a novel class of inhibitors that are currently being assessed in preclinical and clinical studies for cancer treatment.Methods By using a PARG small-molecule inhibitor, COH34, and a cell-penetrating antibody targeting the PARG’s catalytic domain, we investigated the effects of PARG inhibition on signal transducer and activator of transcription 3 (STAT3) in OVCAR8, PEO1, and Brca1-null ID8 ovarian cancer cell lines, as well as in immune cells. We examined PARG inhibition-induced effects on STAT3 phosphorylation, nuclear localization, target gene expression, and antitumor immune responses in vitro, in patient-derived tumor organoids, and in an immunocompetent Brca1-null ID8 ovarian mouse tumor model that mirrors DDR-deficient human high-grade serous ovarian cancer. We also tested the effects of overexpressing a constitutively activated STAT3 mutant on COH34-induced tumor cell growth inhibition.Results Our findings show that PARG inhibition downregulates STAT3 activity through dephosphorylation in ovarian cancer cells. Importantly, overexpression of a constitutively activated STAT3 mutant in tumor cells attenuates PARG inhibitor-induced growth inhibition. Additionally, PARG inhibition reduces STAT3 phosphorylation in immune cells, leading to the activation of antitumor immune responses, shown in immune cells cocultured with ovarian cancer patient tumor-derived organoids and in immune-competent mice-bearing mouse ovarian tumors.Conclusions We have identified a novel antitumor mechanism underlying PARG inhibition beyond its primary antitumor effects through blocking DDR in ovarian cancer. Furthermore, targeting PARG activates antitumor immune responses, thereby potentially increasing response rates to immunotherapy in patients with ovarian cancer.

Abstract Bacterial meningitis (BM) is potentially life threatening in neonates, but the duration of antibiotic therapy is not well established. We aimed to compare the efficacy and safety among neonates suffering from BM of a relatively shortened duration of antibiotic treatment to the currently recommended course. We did a retrospective cohort study in neonates (gestational age [GA] or corrected GA ≥35 weeks) diagnosed with BM. Neonates in the study group were assigned to withdraw the antibiotics on condition that they were clinically stable after taking sufficient antibiotics with normal serological inflammatory biomarkers, whereas the cerebrospinal fluid (CSF) indicators remain abnormal. Neonates in the control group were treated until both serological and CSF indicators returned to normal as recommended. The incidence of recurrent infection after the discontinuation of antibiotics and adverse drug reactions (ADRs) during hospitalization was measured. A total of 233 neonates were enrolled, of whom 160 were assigned to a shortened antibiotic duration and 73 were treated according to the current guidelines. Twelve patients (7.5%) relapsed in the study group, whereas 4 (5.5%) relapsed in the control group (χ2 = 0.320, p = 0.572). The incidences of ADRs were similar in both groups (p > 0.05). The study indicates that antibiotics might be safely discontinued in neonates (GA ≥35 weeks) diagnosed with BM who are clinically stable or improving after antibiotic treatment and feature normal serological inflammatory markers, no severe complications, and no evidence of systemic infection, even if CSF parameters are not completely normal.

Abstract The high-strain dynamic test method possesses the attributes of speed, efficiency, and environmentally-friendly, low-carbon characteristics. To study the reliability of the high-strain dynamic test method in detecting the bearing capacity of pile foundation in permafrost regions, 4 test piles, each with a length of 15 m and a diameter of 1.0 m, were poured based on the actual bridge construction project in the permafrost region of Daxing'an Mountains in China. Based on the temperature data between the piles and soil, the refreezing state of the pile foundation was comprehensively judged. Subsequently, the static method was employed to assess the friction resistance values and single pile bearing capacity of each soil layer on the pile side under different freezing states before and after the pile foundation refreezing. Building upon these findings, the restrictive parameters for soil elastic limit $$q_{(i)}$$ q ( i ) , soil resistance $$R_{U} (i)$$ R U ( i ) and other parameters in the pile-soil model of high-strain dynamic test method are clarified. The test and analysis results indicate that under the condition that the ground temperature of frozen soil is about − 1.9 °C, the pile-soil refreezing takes about 120 days, and the pile-soil refreezing is a slow process; In CAPWAPC calculation program, after the values of soil parameters were constrained by the results of static-load test, the calculated curve is in satisfactory agreement with the measured curve, and the parameters of the pile-soil model are reliable, which can be used for the rapid detection of the ultimate bearing capacity of piles in permafrost regions; In the process of pile-soil refreezing, the change of temperature field affects the freezing strength between pile and soil, the process of pile-soil refreezing is positively correlated with the increase of pile foundation bearing capacity.

In the present work, we pioneered a coordinated self-assembly approach aimed at fabricating carrier-free hybrid nanoparticles to address the inherent challenges of the anaerobic microenvironment and the oxidative resistance induced by reductive glutathione (GSH) in photodynamic therapy (PDT). In these nanoparticles, protoporphyrin IX (PP), HIF-1α inhibitor of N, Nʹ-(2,5-Dichlorosulfonyl) cystamine KC7F2 (KC), and the cofactor Fe3+ present hydrogen bond and coordination interaction. The nanoparticles exhibited efficient cellular uptake by CAL-27 cells, facilitating their accumulation in tumors by enhanced permeability and retention (EPR) effect. Under irradiation at 650 nm, the formation of cytotoxic singlet oxygen (1O2) would be enhanced by the synergy effect on the Fenton reaction of Fe3+ ion and the downregulation of the HIF-1α, leading to the improved PDT efficacy both in vitro and in vivo biological studies. Our work opens a new supramolecular approach to prepare hybrid nanoparticles for effective synergy therapy with PDT against cancer cells.

Abstract The aim of this study was to explore the relationship between serum uric acid (SUA) and the triglyceride-glucose (TyG) index, which is a more effective indicator of insulin resistance. The study participants included 1700 children and adolescents with short stature who were recruited at the Affiliated Hospital of Jining Medical University in China between March 2013 and April 2021. A positive association between SUA levels and the TyG index was detected by univariate analysis (p

Abstract Background Short stature is a common human trait. More severe and/or associated short stature is usually part of the presentation of a syndrome and may be a monogenic disease. The present study aimed to identify the genetic etiology of children with short stature of unknown origin. Methods A total of 232 children with short stature of unknown origin from March 2013 to May 2020 were enrolled in this study. Whole exome sequencing (WES) was performed for the enrolled patients to determine the underlying genetic etiology. Results We identified pathogenic or likely pathogenic genetic variants in 18 (7.8%) patients. All of these variants were located in genes known to be associated with growth disorders. Five of the genes are associated with paracrine signaling or cartilage extracellular matrix in the growth plate, including NPR2 (N = 1), ACAN (N = 1), CASR (N = 1), COMP (N = 1) and FBN1 (N = 1). Two of the genes are involved in the RAS/MAPK pathway, namely, PTPN11 (N = 6) and NF1 (N = 1). Two genes are associated with the abnormal growth hormone-insulin-like growth factor 1 (GH-IGF1) axis, including GH1 (N = 1) and IGF1R (N = 1). Two mutations are located in PROKR2, which is associated with gonadotropin-releasing hormone deficiency. Mutations were found in the remaining two patients in genes with miscellaneous mechanisms: ANKRD11 (N = 1) and ARID1A (N = 1). Conclusions The present study identified pathogenic or likely pathogenic genetic variants in eighteen of the 232 patients (7.8%) with short stature of unknown origin. Our findings suggest that in the absence of prominent malformation, genetic defects in hormones, paracrine factors, and matrix molecules may be the causal factors for this group of patients. Early genetic testing is necessary for accurate diagnosis and precision treatment.

Abstract Aim The purpose of this study was to assess the level of moral courage among nurses in China, and to explore related influential factors, to help nursing managers take measures to improve nurses' moral courage. Design A cross‐sectional study. Methods The data adopted a convenient sampling method. From September to December 2021, 583 nurses from five hospitals in Fujian Province completed the Chinese version of the Nurses' Moral Courage Scale (NMCS). Data were analysed using descriptive statistics, chi‐square test, T‐test, Pearson correlation analysis and multiple regression analysis. Results The Chinese nurses perceived themselves, on average, as morally courageous. The mean NMCS score was 3.64 ± 0.692. The six factors showed statistically significant correlations (p

ObjectivesChildren with medical complexity experienced health disparities during the coronavirus disease 2019 (COVID-19) pandemic. Language may compound these disparities since people speaking languages other than English (LOE) also experienced worse COVID-19 outcomes. Our objective was to investigate associations between household language for children with medical complexity and caregiver COVID-19 vaccine intentions, testing knowledge, and trusted sources of information.MethodsThis cross-sectional survey of caregivers of children with medical complexity ages 5 to 17 years was conducted from April-June 2022. Children with medical complexity had at least 1 Complex Chronic Condition. Households were considered LOE if they reported speaking any language other than English. Multivariable logistic regression examined associations between LOE and COVID-19 vaccine intentions, interpretation of COVID-19 test results, and trusted sources of information.ResultsWe included 1,338 caregivers of children with medical complexity (49% response rate), of which 133 (10%) had household LOE (31 total languages, 58% being Spanish). There was no association between household LOE and caregiver COVID-19 vaccine intentions. Caregivers in households with LOE had similar interpretations of positive COVID-19 test results, but significantly different interpretations of negative results. Odds of interpreting a negative test as expected (meaning the child does not have COVID-19 now or can still get the virus from others) were lower in LOE households (aOR [95% CI]: 0.56 [0.34-0.95]). Households with LOE were more likely to report trusting the US government to provide COVID-19 information (aOR [95% CI]: 1.86 [1.24-2.81]).ConclusionDifferences in COVID-19 test interpretations based on household language for children with medical complexity were observed and could contribute to disparities in outcomes. Opportunities for more inclusive public health messaging likely exist.

IntroductionEndophytes are colonizers of healthy plants and they normally exhibit biocontrol activities, such as reducing the occurrence of plant diseases and promoting plant growth. The endophytic bacterium Bacillus halotolerans Q2H2 (Q2H2) was isolated from the roots of potato plants and was found to have an antagonistic effect on pathogenic fungi.MethodsQ2H2 was identified by morphological observations, physiological and biochemical identification, and 16S rRNA gene sequence analysis. Genes related to the anti-fungal and growth-promoting effects were analyzed using whole-genome sequencing and comparative genomic analysis. Finally, we analyzed the growth-promoting and biocontrol activities of Q2H2 in potato plants using pot experiments.ResultsAntagonism and non-volatile substance plate tests showed that Q2H2 had strong antagonism against Fusarium oxysporum, Fusarium commune, Fusarium graminearum, Fusarium brachygibbosum, Rhizoctonia solani and Stemphylium solani. The plate test showed that Q2H2 had the ability to produce proteases, cellulases, β-1,3-glucanase, dissolved organic phosphate, siderophores, indole-3-acetic acid (IAA), ammonia and fix nitrogen. The suitable growth ranges of Q2H2 under different forms of abiotic stress were pH 5–9, a temperature of 15–30°C, and a salt concentration of 1–5%. Though whole-genome sequencing, we obtained sequencing data of approximately 4.16 MB encompassed 4,102 coding sequences. We predicted 10 secondary metabolite gene clusters related to antagonism and growth promotion, including five known products surfactin, bacillaene, fengycin, bacilysin, bacillibactin, and subtilosin A. Average nucleotide identity and comparative genomic analyses revealed that Q2H2 was Bacillus halotolerans. Through gene function annotation, we analyzed genes related to antagonism and plant growth promotion in the Q2H2 genome. These included genes involved in phosphate metabolism (pstB, pstA, pstC, and pstS), nitrogen fixation (nifS, nifU, salA, and sufU), ammonia production (gudB, rocG, nasD, and nasE), siderophore production (fhuC, fhuG, fhuB, and fhuD), IAA production (trpABFCDE), biofilm formation (tasA, bslA, and bslB), and volatile compound production (alsD, ilvABCDEHKY, metH, and ispE), and genes encoding hydrolases (eglS, amyE, gmuD, ganB, sleL, and ydhD). The potato pot test showed that Q2H2 had an obvious growth-promoting effect on potato roots and better control of Fusarium wilt than carbendazim.ConclusionThese findings suggest that the strain-specific genes identified in bacterial endophytes may reveal important antagonistic and plant growth-promoting mechanisms.

Abstract Background Empagliflozin, a sodium–glucose co-transporter 2 inhibitor (SGLT2i), has been reported to significantly reduce the risk of heart failure in multiple clinical studies. However, the underlying mechanisms remain elusive. This study aimed to investigate the effect of empagliflozin on branched-chain amino acid (BCAA) metabolism in diabetic cardiomyopathy. Methods Thirty male 8-week KK Cg-Ay/J mice were used to study diabetic cardiomyopathy; here, 15 were used as the model group, and the remaining 15 were administered empagliflozin (3.75 mg/kg/day) by gavage daily for 16 weeks. The control group consisted of fifteen male 8-week C57BL/6J mice, whose blood glucose and body weight were measured simultaneously with the diabetic mice until 16 weeks without additional intervention. Echocardiography and histopathology were performed to evaluate cardiac structure and function. Proteomic sequencing and biogenic analysis were performed on mouse hearts. Parallel Reaction Monitoring and western blotting were performed to validate the expression levels of differentially expressed proteins. Results The results showed that empagliflozin improved ventricular dilatation and ejection fraction reduction in diabetic hearts, as well as the elevation of myocardial injury biomarkers hs-cTnT and NT-proBNP. At the same time, empagliflozin alleviates myocardial inflammatory infiltration, calcification foci deposition, and fibrosis caused by diabetes. The results of the proteomics assay showed that empagliflozin could improve the metabolism of various substances, especially promoting the BCAA metabolism of diabetic hearts by up-regulating PP2Cm. Furthermore, empagliflozin could affect the mTOR/p-ULK1 signaling pathway by reducing the concentration of BCAA in diabetic hearts. When mTOR/p-ULK1 protein was inhibited, ULK1, the autophagy initiation molecule, increased. Moreover, autophagy substrate p62 and autophagy marker LC3B were significantly reduced, indicating that the autophagy activity of diabetes inhibition was reactivated. Conclusions Empagliflozin may attenuate diabetic cardiomyopathy-related myocardial injury by promoting the catabolism of BCAA and inhibiting mTOR/p-ULK1 to enhance autophagy. These findings suggest that empagliflozin could be a potential candidate drug against BCAA increase and could be used for other cardiovascular diseases with a metabolic disorder of BCAA.

Abstract Background Oxidized soybean oil (OSO) has been shown to impair growth and exacerbate inflammation, leading to intestinal barrier injury in animals. Recent evidence suggests important roles for resveratrol (RES) in the promoting growth performance, antioxidant capacity, anti-inflammatory, and regulate intestinal barriers in animals. Therefore, The objectives of this study are to investigate the effects of dietary RES (purity 98%) supplementation on the growth performance, antioxidant capacity, inflammatory state, and intestinal function of weaned piglets challenged with OSO. Methods A total of 28 castrated weaned male piglets with a similar body weight of 10.19 ± 0.10 kg were randomly assigned to 4 dietary treatments for 28-d feeding trial with 7 replications per treatment and 1 piglet per replicate. Treatments were arranged as a 2 × 2 factorial with oil type [3% fresh soybean oil (FSO) vs. 3% OSO] and dietary RES (0 vs. 300 mg/kg). Results The results showed that relative to the FSO group, OSO stress tended to decrease the average daily feed intake (ADFI), and decreased the activity levels of lipase, villus/crypt ratio (VCR), the mRNA expression of FABP1, SOD2, IL-10 and ZO-1 in the jejunum, and SOD2, GPX1, occludin and ZO-1 in the colon, the levels of acetic acid in the colonic digesta, whereas up-regulated the mRNA expression of IL-1β and TNF-α in the jejunum (P

Abstract Background The updated estimates of hepatitis C virus (HCV) seroprevalence are critical for developing strategies to manage or eliminate HCV infection. Methods A comprehensive study on HCV seroprevalence was conducted among 365,210 patients at Jinan Central Hospital, China, from 2008 to 2020. The patients were tested for anti-HCV, HCV core antigen, hepatitis B surface antigen, syphilis antibody, human immunodeficiency virus antigen + antibody, antihepatitis A virus IgM, and antihepatitis E virus IgM. Results HCV seroprevalence was 0.79% and was related to age. HCV seropositivity was lower in children (aged

BackgroundHeart failure with preserved ejection fraction (HFpEF) is associated with changes in cardiac metabolism that affect energy supply in the heart. However, there is limited research on energy metabolism-related genes (EMRGs) in HFpEF.MethodsThe HFpEF mouse dataset (GSE180065, containing heart tissues from 10 HFpEF and five control samples) was sourced from the Gene Expression Omnibus database. Gene expression profiles in HFpEF and control groups were compared to identify differentially expressed EMRGs (DE-EMRGs), and the diagnostic biomarkers with diagnostic value were screened using machine learning algorithms. Meanwhile, we constructed a biomarker-based nomogram model for its predictive power, and functionality of diagnostic biomarkers were conducted using single-gene gene set enrichment analysis, drug prediction, and regulatory network analysis. Additionally, consensus clustering analysis based on the expression of diagnostic biomarkers was utilized to identify differential HFpEF-related genes (HFpEF-RGs). Immune microenvironment analysis in HFpEF and subtypes were performed for analyzing correlations between immune cells and diagnostic biomarkers as well as HFpEF-RGs. Finally, qRT-PCR analysis on the HFpEF mouse model was used to validate the expression levels of diagnostic biomarkers.ResultsWe selected 5 biomarkers (Chrna2, Gnb3, Gng7, Ddit4l, and Prss55) that showed excellent diagnostic performance. The nomogram model we constructed demonstrated high predictive power. Single-gene gene set enrichment analysis revealed enrichment in aerobic respiration and energy derivation. Further, various miRNAs and TFs were predicted by Gng7, such as Gng7-mmu-miR-6921-5p, ETS1-Gng7. A lot of potential therapeutic targets were predicted as well. Consensus clustering identified two distinct subtypes of HFpEF. Functional enrichment analysis highlighted the involvement of DEGs-cluster in protein amino acid modification and so on. Additionally, we identified five HFpEF-RGs (Kcnt1, Acot1, Kcnc4, Scn3a, and Gpam). Immune analysis revealed correlations between Macrophage M2, T cell CD4+ Th1 and diagnostic biomarkers, as well as an association between Macrophage and HFpEF-RGs. We further validated the expression trends of the selected biomarkers through experimental validation.ConclusionOur study identified 5 diagnostic biomarkers and provided insights into the prediction and treatment of HFpEF through drug predictions and network analysis. These findings contribute to a better understanding of HFpEF and may guide future research and therapy development.

BackgroundEvidence regarding the relationship between sleep duration and blood pressure is controversial. Therefore, the aim of this study was to investigate the relationship between sleep duration and blood pressure in children with short stature.MethodsA total of 1,085 participants with short stature were enrolled from the Affiliated Hospital of Jining Medical University in China. The variables involved in this study included sleep duration, anthropometric indicators and biochemical parameters. Sleep duration was evaluated in a face-to-face interview.ResultsThe average age of the 1,085 selected participants was 10.2 ± 3.5 years old, and approximately 763 (70.32%) of them were male. The results of adjusted linear regression showed that sleep duration was negatively associated with systolic blood pressure z scores (SBP-Z) and diastolic blood pressure z scores (DBP-Z) after adjusting for confounders (β −0.07, 95% CI −0.13, −0.01 P = 0.038; β −0.05, 95% CI −0.10, −0.01 P = 0.035, respectively). A nonlinear relationship was detected between sleep duration and blood pressure, including SBP-Z, DBP-Z and mean arterial pressure z scores (MAP-Z). The inflection point of the nonlinear relationship between sleep duration and SBP-Z is 10 h, and the inflection point of DBP-Z and MAP-Z is 8 h.ConclusionThis study revealed a nonlinear relationship between sleep duration and blood pressure in children with short stature. The findings suggest that the optimal sleep duration in children with short stature was 8–10 h, and sleep durations either too short or too long were associated with increased blood pressure levels.

Mining community structure in attribute network is helpful to further analysis of network nodes, which has important practical significance. Graph convolution neural network can effectively embed the structural information of attribute network and obtain the feature representation of nodes. Based on this, the community structure with good performance can be obtained. However, most of the existing graph convolution methods use fixed low-order graph convolution, only consider the first-order or second-order neighbors of each node, don’t make full use of the node relationship and ignore the diversity of network structure. In addition, the sparsity of the original network structure can’t be overcome, which will reduce the performance of community detection. In order to solve the above problems, this paper proposes a K-order graph convolution community detection method (KGCN) which combines attribute information and structure information. This method can effectively overcome the sparsity of the original network and use the high-order structure of nodes for community detection. Firstly, the original network is reconstructed according to the attribute information of nodes to alleviate the sparsity of the original network. Secondly, considering the high-order structure correlation, the K-order graph convolution encoder is used to encode the nodes to obtain the feature representation of the nodes. Finally, community detection is carried out using spectral clustering algorithm. Experimental results show that the KGCN method achieves better community detection results than the existing algorithms on four real datasets.

Abstract Objective To provide a rare case of local recurrent Paget’s disease after nipple-sparing mastectomy (NSM) with immediate breast reconstruction with 10 years of disease-free survival and to analyze the clinical and pathological characteristics. Background Mammary Paget’s disease can be considered a rare type of local recurrence after breast cancer treatment, both in cases of conservative surgery and NSM with immediate breast reconstruction (Lohsiriwat et al, Ann Surg Oncol 19:1850-1855, 2012). Recurrent patients who present with nipple-areolar Paget’s disease usually have unfavorable primary pathological characteristics and different latency periods. However, the recurrent status in patients with favorable primary pathological characteristics and the latency periods after NSM with immediate breast reconstruction are unclear. Methods First, we present a case of local recurrent Paget’s disease in a young patient diagnosed with invasive breast carcinoma at age 30 who underwent NSM with primary silicone reconstruction. Then, the keywords “Paget’s disease” and “nipple-sparing mastectomy” were selected. Articles including the local recurrence of Paget’s disease after NSM were collected from the PubMed, Springer, and OVID databases, and the acquired relevant data were analyzed. We did not restrict our search by study design or publication date. Results Five studies describing 31 cases of local recurrent Paget’s disease after NSM with implant breast reconstruction were included. The mean patient age reported was 45 years, and the average latency period from NSM to the local recurrence of Paget’s disease was 40.2 months. Recurrent tumor histological features were Paget’s disease with ductal carcinoma in situ (DCIS) in 16 patients (50%), Paget’s disease without DCIS in 13 patients (40.6%), and Paget’s disease with ductal intraepithelial neoplasia (DIN) in 3 patients (9.4%). The primary tumor histological feature was estrogen receptor (ER)(−)/progesterone receptor (PR)(−)/human epidermal growth factor receptor (HER-2)(+) in 21 patients (77.8%). Neither locoregional relapse nor metastatic events were found in these recurrent patients who accepted NAC excision after 4–5 years of follow-up. Our reported case showed that the patient experienced pregnancy and lactation after primary adjuvant chemotherapy and endocrine therapy. However, she developed an eczematoid lesion in the NAC 120 months after breast surgery. The histopathological examination was consistent with Paget’s disease of the breast. Complete NAC and breast silicone prosthesis removal were performed. The patient accepted no systematic or local therapy and is currently alive. It is noteworthy that the biological features of the primary tumor were ER(+), PR(+), and HER-2(−); however, the recurrent tumor changed to ER(−), PR(−), and HER-2(+). Conclusions The local recurrence of Paget’s disease after NSM is uncommon; it may develop at a very early age and have a very long time to recurrence, as in our patient, who presented with recurrence 10 years after primary surgery. Surgeons should be wary of local recurrence of the nipple-areola complex after NSM in patients with ER-negative and HER-2-positive primary tumors. However, patients with ER/PR-positive and HER-2-negative tumors should not be neglected; we reported a case of an ER/PR-positive and HER-2-negative primary tumor, and ER-positive recurrent cases have the longest latency period. The local recurrence rate of Paget’s disease after NSM is low, and the prognosis is good in recurrent patients who accept further extensive NAC excision. Further systematic treatment was not considered for this patient.

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly pathogenic to humans and has caused the ongoing coronavirus disease 2019 (COVID-19) pandemic. Vaccines are one of the efficient ways to prevent the viral infection. After COVID-19 vaccination, the monitoring of the dynamic change in neutralizing antibodies is necessary to determine booster requirements.MethodsWe estimated the effectiveness of the inactivated vaccines by monitoring dynamic SARS-CoV-2 neutralizing antibodies for over 2 years. Additionally, we also investigated the activation of T lymphocytes (CD3+ T cells) after three doses of the inactivated vaccine.ResultThe results showed that the rate of reduction of SARS-CoV-2 neutralizing antibody levels gradually showed after each booster dose. The IgG/IgM level at 9 months after the third vaccination were significantly higher than those at 6 months after the second dose (p

As urbanization exposes wildlife to new challenging conditions and environmental pressures, species that exhibit a high degree of behavioral plasticity are considered potentially capable of colonizing and adapting to urban environments. However, differences in the behavior of populations that inhabit urban and suburban landscapes pose unprecedented challenges to traditional methods in wildlife management which often fail to consider a species’ needs or mitigate human–wildlife conflict due to changes in species behavior in response to intensive human interference. Here, we investigate differences in the home range, diel activity, movement, and diet of raccoon dogs ( Nyctereutes procyonoides ) between residential districts and forest park habitats in Shanghai, China. Using GPS tracking data from 22 individuals, we find that the home ranges of raccoon dogs in residential districts (10.4 ± 8.8 ha) was 91.26% smaller than those in forest parks (119.6 ± 135.4 ha). We also find that raccoon dogs in residential districts exhibited significantly lower nocturnal movement speeds (134.55 ± 50.68 m h ^−1 ) compared to their forest park counterparts (263.22 ± 84.972 m h ^−1 ). An analysis of 528 fecal samples showed a significantly higher intake of ingredients from human food in residential districts ( χ ^2 = 4.691, P = 0.026), which indicates that urban raccoon dog foraging strategies differ from the forest park population due to the presence of discarded human food, cat food, and wet garbage in residential districts. Based on our findings, we propose a community-based wildlife management strategy and suggest modifying the current design of residential districts. Our results underscore the importance of mammal behavior studies in urban biodiversity management and provide a scientific basis for mitigating human–wildlife conflicts in urban environments in and beyond our study area.

Hypomanic symptoms in postpartum women are common but often ignored due to under diagnosis, which may lead to more serious psychological problems, such as postpartum depression and bipolar disorder. We reviewed recent advances in diagnostic criteria and assessment tools regarding postpartum hypomanic symptoms as well as their relationship with postpartum depression and bipolar disorder, aiming to provide physicians and nurses with a scientific basis for more effectively identifying postpartum hypomania.

Abstract Background Although obesity has been associated with risk of atrial fibrillation (AF), the associations of variability of obesity measures with AF risk are uncertain, and longitudinal studies among Chinese population are still lacking. We aimed to evaluate the impacts of obesity and variability of body mass index (BMI) and waist circumference (WC) on the risk of atrial fibrillation (AF) in a large Chinese cohort study. Methods A total of 44,135 participants of the Kailuan Study who were free of cancer and cardiovascular disease and underwent three consecutive surveys from 2006 to 2010 were followed for incident AF until 2020. Average BMI and WC over time and variability were calculated. Cox proportional hazards regression models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of obesity and variability in BMI and WC with AF risk. Results During a mean follow-up of 9.68 years, there were 410 cases of incident AF. In multivariable-adjusted models, compared with normal BMI/WC, individuals with general obesity and abdominal obesity had increased risk of AF, with corresponding HRs of 1.73 (95% CI: 1.31–2.30) and 1.38 (95% CI: 1.11–1.60), respectively. The short-term elevation in AF risk persisted for the obese even after adjustment for updated biologic intermediaries and weight. Variability in BMI and WC were not associated with the risk of AF. The restricted cubic spline models indicated significant linear relationships between levels of WC and BMI and risk of AF. Conclusions Elevated levels of BMI and WC were associated with an increased risk of AF, whereas variability in BMI and WC were not. Therefore, achieving optimal levels of BMI and WC could be valuable in AF prevention.

Summary: The genetic improvement of economic traits suggests that chicken is an excellent model for exploring the genetic changes and molecular mechanisms underlying phenotypic diversity and artificial selection. Here, the sequencing data including 477 samples from 25 breeds worldwide were used to reveal the genomic patterns of chicken domestication. We analyzed 7.4 Tb clean data with 14.8× per individual to identify 23,504,766 SNPs, 3,289,782 InDels, and 27,027 SVs. The diversity analysis indicates that high-intensity artificial selection would accelerate population differentiation. We also found that the human-driven traits are controlled by polygenes and major genes, such as the primary candidates SOX5 and IGF1 for body size, and NEDD4 for sperm storage capacity. Our findings provide an important reference for understanding how genomic patterns shape phenotypes in livestock.

In order to investigate the migration amounts of bisphenol substances (BPs) in domestic food metal cans, a method of simultaneous detection of 14 kinds of BPs in food metal cans with high sensitivity was established by high performance liquid chromatography (HPLC). The effect of sterilization process on the migration of BPs and the migration laws of BPs in food metal cans were studied. Results showed that, all the 14 kinds of BPs were well separated and exhibited excellent linear characteristics in four kinds of food simulants (4 vol% acetic acid, 10 vol% ethanol, 50 vol% ethanol and isooctane). The precision and accuracy of the method was excellent with the recovery of the 14 kinds of BPs from 83.67%～107.05% and the relative standard deviations (RSDs) from 2.32%～7.67%, indicating that HPLC method was effective for simultaneous determination of 14 kinds of BPs in food metal cans. The amounts of 14 kinds of BPs migrated from nine kinds of canned foods and beverages on the Chinese market were simultaneously determined, and found seven kinds of BPs were detected while no BPA and its analogues were detected in all samples. BADGE·H2O migrating from the luncheon meat can, BADGE·2H2O migrating from the oyster pueraria beverage can and BFDGE·2H2O migrating from the blackberry all had the risk according to EU regulation. In addition, the sterilization process affected the amounts and types of BPs migrating from the food metal cans. After migration tests, only BADGE·2H2O was detected in sterilized cans while both BADGE·2H2O and BADGE·H2O·HCl were detected in unsterilized cans. Moreover, the type of food simulants also affected the amount and types of BPs migrating from food metal cans. With the increasing of migration temperature or time, the migration amounts of BPs increased at first and finally kept steady when the migration reached equilibrium.

Abstract Background Chronic granulomatous disease (CGD) is an inborn error of immunity. It is characterized by recurrent bacterial or fungal infections, including infections by Burkholderia species. This is due to respiratory burst dysfunction of phagocytes. Currently, there is no report on Burkholderia contaminans (B. Contaminans) infection in children with CGD. Case presentation We present a previously healthy, 17-month-old Chinese boy infected with B. Contaminans in the intra-abdominal regions. Immunological screening, including assessment of cellular immunity and humoral immunity did not yield conclusive results. The level of nicotinamide adenine dinucleotide phosphatase (NADPH) activity was decreased and whole-exome sequencing identified a de novo mutation in the CYBB gene. Conclusions For specific pathogens such as B. Contaminans, immune assessment should be carried out even if there is no positive medical history or specificity in basic immunity screening.

OBJECTIVE To investigate thermoregulation, thermal antinociception, food/kaolin intake, fecal output, and behavior following long-acting buprenorphine preparations in rats. ANIMALS 8 adult male rats (Rattus norvegicus) were administered long-acting SC buprenorphine (SB; 0.65 mg/kg), transdermal buprenorphine (TB; 10 mg/kg), and controls in a randomized, cross-over design. METHODS Body temperature, self-injury, sedation, food/kaolin intake, fecal output, and thermal withdrawal latencies were measured 1, 4, 8, 12, 24, 48, and 72 hours posttreatment. Data analysis was performed with mixed linear models. RESULTS Self-injury was present between 1 and 12 hours and 4 and 12 hours following TB and SB, respectively; sedation was associated with TB at 12 to 24 hours. Withdrawal latencies were longer in both TB and SB groups than in the control group. Food intake decreased with time in all groups but was significantly lower 24 to 48 hours after TB and 24 to 72 hours after SB versus controls. Kaolin intake decreased from baseline 48 to 72 hours in the control group. Fecal output decreased from baseline 24 to 72 hours in all groups but was significantly lower than controls 24 hours following TB and 24 to 48 hours in SB. Body temperature increased from baseline at 1 hour, 1 to 12 hours, and 1 to 24 hours in the control, TB, and SB groups, respectively, and was significantly higher than the control group 1 to 72 hours following TB and 4 to 24 hours after SB. Transdermal buprenorphine and SB in normal rats produced antinociception, self-injurious behavior, hyperthermia, and decreased food/fecal output. CLINICAL RELEVANCE Although these buprenorphine preparations may produce antinociception, untoward effects such as hyperthermia, self-injurious behavior, and reduced food intake/fecal output may be seen. [ABSTRACT FROM AUTHOR]

Soybean seeds show great potential as a safe and cost-effective host for the large-scale production of biopharmaceuticals and industrially important macromolecules. However, the yields of desired recombinant proteins in soybean seeds are usually lower than the economic threshold for their potential commercialization. Our previous study demonstrated that polypeptide fusion such as maize γ-zein or elastin-like polypeptide (ELP) could significantly increase the accumulation of foreign proteins. In the present study, a recombination strategy of polypeptide fusions (γ-zein or ELP) and suppression of intrinsic storage proteins (glycinin or conglycinin) via RNA interference was further exploited to improve the yield of the target protein in soybean seeds. Transgenic soybean plants harboring both polypeptide-fused green fluorescent protein (GFP) and glycinin/conglycinin RNAi expression cassettes were generated and confirmed by molecular analysis. The results showed that on both the glycinin and conglycinin suppression backgrounds, the average accumulation levels of recombinant zein-GFP and GFP-ELP proteins were significantly increased as compared to that of their counterparts without such suppressions in our previous study. Moreover, zein-GFP and GFP-ELP accumulation was also remarkably higher than unfused GFP on the glycinin suppression background. However, no significant differences were detected in the glycinin or conglycinin suppression backgrounds for the same polypeptide fusion constructs, though suppression of one of the storage proteins in soybean seeds led to a significant increase in the other. Additionally, the increases in the recombinant protein yield did not affect the total protein content and the protein/oil ratio in soybean seeds. Taken together, the results indicate that both the fusion of the foreign protein with polypeptide tags together with the depletion of endogenous storage proteins contributed to a higher accumulation of the recombinant proteins without affecting the total protein content or the protein/oil ratio in soybean seeds.

Cephalopods are an essential component of marine ecosystems, which are of great significance for the development of marine resources, ecological balance, and human food supply. At the same time, the preservation of cephalopod resources and the promotion of sustainable utilization also require attention. Many studies on the classification of cephalopods focus on the analysis of their beaks. In this study, we propose a feature fusion-based method for the identification of beaks, which uses the convolutional neural network (CNN) model as its basic architecture and a multi-class support vector machine (SVM) for classification. First, two local shallow features are extracted, namely the histogram of the orientation gradient (HOG) and the local binary pattern (LBP), and classified using SVM. Second, multiple CNN models were used for end-to-end learning to identify the beaks, and model performance was compared. Finally, the global deep features of beaks were extracted from the Resnet50 model, fused with the two local shallow features, and classified using SVM. The experimental results demonstrate that the feature fusion model can effectively fuse multiple features to recognize beaks and improve classification accuracy. Among them, the HOG+Resnet50 method has the highest accuracy in recognizing the upper and lower beaks, with 91.88% and 93.63%, respectively. Therefore, this new approach facilitated identification studies of cephalopod beaks.

Lung cancer is one of the most common cancers around the world, with a high mortality rate. Despite substantial advancements in diagnoses and therapies, the outlook and survival of patients with lung cancer remains dismal due to drug tolerance and malignant reactions. New interventional treatments urgently need to be explored if natural compounds are to be used to reduce toxicity and adverse effects to meet the needs of lung cancer clinical treatment. An internalizing arginine-glycine-aspartic acid (iRGD) modified by a tumour-piercing peptide liposome (iRGD-LP-CUR-PIP) was developed via co-delivery of curcumin (CUR) and piperine (PIP). Its antitumour efficacy was evaluated and validated via in vivo and in vitro experiments. iRGD-LP-CUR-PIP enhanced tumour targeting and cellular internalisation effectively. In vitro, iRGD-LP-CUR-PIP exhibited enhanced cellular uptake, suppression of tumour cell multiplication and invasion and energy-independent cellular uptake. In vivo, iRGD-LP-CUR-PIP showed high antitumour efficacy, mainly in terms of significant tumour volume reduction and increased weight and spleen index. Data showed that iRGD peptide has active tumour targeting and it significantly improves the penetration and cellular internalisation of tumours in the liposomal system. The use of CUR in combination with PIP can exert synergistic antitumour activity. This study provides a targeted therapeutic system based on natural components to improve antitumour efficacy in lung cancer.

IntroductionTP73 was recently identified as a novel causative gene for amyotrophic lateral sclerosis (ALS). We aimed to determine the contribution of variations in TP73 in the Chinese ALS population and to further explore the genotype-phenotype correlations.MethodsWe screened rare, putative pathogenic TP73 mutations in a large Chinese ALS cohort and performed association analysis of both rare and common TP73 variations between cases and controls.ResultsOf the 985 ALS patients studied, six rare, heterozygous putative pathogenic variants in TP73 were identified among six unrelated sALS patients. Exon 14 of TP73 might be a mutant hotspot in our cohort. Patients with ALS with only rare, putative pathogenic TP73 mutations exhibited a characteristic clinical profile. Patients harboring multiple mutations in TP73 and other ALS-related genes displayed a significantly earlier onset of ALS. Association analysis revealed that rare TP73 variants in the untranslated regions (UTRs) were enriched among ALS patients; meanwhile, two common variants in the exon-intron boundary were discovered to be associated with ALS.DiscussionWe demonstrate that TP73 variations also have contributed to ALS in the Asian population and broaden the genotypic and phenotypic spectrum of TP73 variants in the ALS-frontotemporal dementia (FTD) spectrum. Furthermore, our findings first suggest that TP73 is not only a causative gene, but also exerts a disease-modifying effect. These results may contribute to a better understanding of the molecular mechanism of ALS.

ObjectiveUric acid to high-density lipoprotein cholesterol ratio (UHR), the ratio of uric acid to high-density lipoprotein cholesterol, is a newly proposed marker of metabolic abnormalities. There are few previous studies directly investigating the relationship between UHR and alanine aminotransferase (ALT), especially in short stature populations, however, short stature children and adolescents are more likely to have metabolic disorders. This research aimed to investigate the relationship between the UHR and ALT in children and adolescents with short stature.MethodsIn this cross-sectional analysis, the clinical data of 1,510 children with height below −2 SD who were evaluated at the Department of Endocrinology, Affiliated Hospital of Jining Medical University from 1 March 2013 to 31 December 2021, were selected. Anthropometric and biochemical indicators were measured. The relationship between UHR and ALT was analysed.ResultsThe univariate analysis results showed that UHR was positively associated with ALT (β = 0.43, P < 0.0001). Furthermore, after adjusting for possible confounding factors, a non-linear relationship was detected between UHR and ALT through smooth curve fitting, and the inflection point of UHR was 10.93% after multivariate piecewise linear regression analysis. ALT increased with UHR elevation when the UHR was greater than 10.93% (β = 0.69, 95% CI 0.39, 0.98; P < 0.0001). However, we did not observe a significant relationship when the UHR was less than 10.93% (P = 0.9229).ConclusionOur study demonstrated that in Chinese children and adolescents with short stature, UHR may be associated with the regulation of ALT levels, and this relationship merits further investigation.

BackgroundAs the COVID-19 epidemic was gradually brought under control, a new autumn semester began in 2020. How was the mental health of postgraduates as they experienced quarantine at home, only commuting between the school and hospital?MethodsThe research was conducted in a cross-sectional online survey in October 2020. The data were collected from 1,645 medical postgraduates (master’s and doctoral students) by using the demographic information questionnaire, the Self-rating Depression Scale (SDS), the Self-rating Anxiety Scale (SAS), the Questionnaire on Psychological Stressors of Postgraduates (QPSP), the Simplified Coping Style Questionnaire (SCSQ) and the Social Support Rate Scale (SSRS). One-way ANOVA and Pearson correlation were used to explore the relationships among anxiety, depression, psychological stressors, social support and coping style. Structural equation modeling (SEM) was conducted to assess the mediation model.ResultsAmong the total of 1,645 medical postgraduates, 21.6% (n = 356) had self-rated depression symptoms, and 9.4% (n = 155) had self-rated anxiety symptoms. The main disturbances they experienced were employment, academic and interpersonal pressure. The master of third grade students had the highest employment pressure, and the master of second grade students had the highest academic and interpersonal pressure. Negative coping played a negative mediating role and social support played a positive mediating role in the relationships between perceived stress and anxiety (β = 0.027, P < 0.01; β = 0.124, P < 0.01) and depression (β = 0.016, P < 0.01; β = 0.193, P < 0.01).ConclusionMedical postgraduates in China restricted to studies on campus and in the hospital experienced psychological distress. Our results suggest that providing employment and learning guidance, while strengthening social support and guiding positive coping may be effective at improving the mental health of the medical graduate students, mediating their perceived stress and negative emotions.

IntroductionWith the population aging, osteoporosis has become a major public health concern. Elevated oxidative stress is a vital detrimental factor for bone health. Compared to common oxidative stress-related biomarkers, Fluorescent Oxidation Products (FlOPs) reflect the global levels of oxidation from proteins, lipids, and DNA. Nevertheless, whether plasma FlOP levels are related to bone health measured by Quantitative ultrasound (QUS) is unclear. Thus, the present study examined the association between FlOPs and QUS parameters in middle-aged and elderly adults.MethodsThis community-based cross-sectional study was conducted in Changchun, northeast China. Plasma FlOPs were determined by a fluorescent microplate reader at a wavelength of 320/420 nm (excitation/emission). QUS parameters [speed of sound (SOS) and broadband ultrasound attenuation (BUA)] of the calcaneus were assessed by an ultrasound bone densitometer. We used multivariable linear regression to examine the association between FlOPs and QUS parameters.ResultsA total of 491 subjects were included in this study. Their average age was 65.2 years (standard deviation [SD]: 9.7 years). FlOPs were inversely associated with SOS (β for an increase of logarithmic interquartile range = −10.64; P = 0.018). Higher FlOP levels were marginally associated with lower SOS in females (β for an increase of logarithmic interquartile range = −9.68, P = 0.066), but not in males (β for an increase of logarithmic interquartile range = −11.84, P = 0.131). No significant relationship between FlOPs and BUA was observed.ConclusionsPlasma FlOP levels were inversely associated with SOS, but not with BUA in middle-aged and elderly adults.

IntroductionEndophytes are non-pathogenic inhabitants of healthy plant tissues and have been found to promote plant growth and health. The endophytic bacterial strain Q2H1 was isolated from the roots of the potato and was identified to exhibit growth-promoting effects in potato plants.MethodsWhole-genome sequencing was performed to reveal the mechanism underlying its growth-promoting effect. The obtained sequencing data of approximately 5.65 MB encompassed 5,533 coding sequences. Of note, nine secondary metabolite gene clusters, including siderophore gene clusters, closely associated with plant growth promotion (PGP) were predicted by antiSMASH software. Comparative genomic analysis revealed that Q2H1 belongs to the genus Peribacillus. By gene function annotation, those genes related to plant growth-promoting activities, including indole-3-acetic acid (IAA) synthesis in tryptophan metabolism, siderophore biosynthetic activity, phosphate solubilization, nitrogen fixation, and related genes, were summarized. IAA (14.4 μg/ml) was presumptively produced by Q2H1 using the Salkowski colorimetric method. A total of five genes, namely, phoU, pstB, pstA1, pstC, and pstS, were annotated for phosphate solubilization, which is associated with the ability of the Q2H1 strain to solubilize phosphate under in vitro conditions.ResultsIt is revealed that genes in the Q2H1 genome associated with nitrogen fixation belonged to three groups, namely, nitrogen fixation (nifU, sufU, salA, and nifS), nitrogen metabolism (nirA, nrtB, and nasA), and glutamate synthesis (glnA, gltB, gltD, and gudB), supported by evidence that Q2H1 grew on medium without nitrogen. We have also identified a siderophore gene cluster located on the chromosome of Q2H1, including seven genes (viz., rbsR, rhbf, rhbE, rhbD, rhbC, rhbA, ddc, and an unknown gene). In the in vitro assay, a prominent brown circle around the colony was produced on the chrome azurol S medium at 48 and 72 h post-inoculation, indicating that the siderophore gene cluster in Q2H1 harbored the ability to produce siderophores.ConclusionIn summary, these findings implied that identifying strain-specific genes for their metabolic pathways in bacterial endophytes may reveal a variety of significant functions of plant growth-promoting mechanisms.

Abstract Background Osteoporosis and cardiovascular diseases (CVDs) are 2 major public health problems. Osteoporosis and CVDs may be linked but the association between lipid profile and osteoporosis is still controversial. The purpose of this study was to examine the associations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) with osteoporosis. Methods Using inpatients’ and outpatients’ electronic medical records (EMR) and dual X-ray absorptiometry (DXA) database stored at The Second Hospital of Jilin University, we included 481 individuals with complete and valid lipid and bone mineral density (BMD) data in 2017. Serum samples were used to measure TC, LDL-C, HDL-C and TG. Femoral neck and total hip BMD were measured by DXA; osteoporosis was defined as femoral neck or total hip T-score ≤ -2.5. Multivariable logistic regression models were used to test the associations of TC, LDL-C, HDL-C and TG with osteoporosis. Results The mean age for included individuals was 62.7 years (SD = 8.6 years); 60.1 % of them were female. Each standard deviation (SD) increase in TC (Odds Ratio [OR]: 1.48; 95 % Confidence Interval [CI]: 1.06–2.07) and TG (OR: 1.67; 95 % CI: 1.16–2.39) were associated with increased risk of osteoporosis; LDL-C and HDL-C levels were not associated with osteoporosis. Age, sex and body mass index (BMI) did not interact with the relationships of TC and TG with osteoporosis (all P > 0.10). Conclusions Higher TC and TG levels were associated with greater risk of osteoporosis in this cross-sectional study.