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Abstract Background Glioblastoma (GBM) is a malignant astrocytic tumor and its progression involves the regulation of vascular endothelial growth factor-A (VEGFA). However, the mechanism of VEGFA in regulating GBM progression remains unclear. Methods VEGFA mRNA expression was analyzed by quantitative real-time polymerase chain reaction. Protein expression of VEGFA, cluster of differentiation 9 (CD9), CD81, and transforming growth factor-β1 (TGF-β1) was detected by western blotting assay. Flow cytometry assay was conducted to assess cell proliferation, cell apoptosis and myeloid-derived suppressor cell (MDSC) differentiation. TUNEL cell apoptosis detection kit was utilized to analyze cell apoptosis of tumors. Angiogenic capacity was investigated by tube formation assay. Transwell assay was used to assess cell migration and invasion. The effect of VEGFA on tumor formation was determined by a xenograft mouse model assay. Immunohistochemistry assay was used to analyze positive expression rate of VEGFA in tumor tissues. TGF-β1 level was detected by enzyme-linked immunosorbent assay. Results VEGFA expression was upregulated in GBM tissues, GBM cells, and exosomes from GBM patients and GBM cells. VEGFA silencing led to decreased cell proliferation, tube formation, migration and invasion and increased cell apoptosis. Moreover, VEGFA knockdown also delayed tumor formation. VEGFA promoted MDSC differentiation and TGF-β1 secretion by MDSCs by being packaged into exosomes. In addition, TGF-β1 knockdown displayed similar effects with VEGFA silencing on GBM cell phenotypes, and MDSCs attenuated VEGFA knockdown-induced effects by secreting TGF-β1 in A172 and U251 cells. Conclusion VEGFA contributed to tumor property of GBM cells by promoting MDSC differentiation and TGF-β1 secretion by MDSCs, providing potential targets for GBM treatment.

Abstract Background The leading cause of end-stage renal disease (ESRD) is diabetic nephropathy (DN). Podocyte damage is an early event in the development of DN. Currently, there is no effective treatment strategy that can slow the progression of DN or reverse its onset. The role of mesenchymal stem cells (MSCs) transplantation in diabetes and its complications has been extensively studied, and diabetic nephropathy has been a major focus. Irbesartan exerts reno-protective effects independent of lowering blood pressure, can reduce the incidence of proteinuria in rats, and is widely used clinically. However, it remains undetermined whether the combined utilization of the angiotensin II receptor antagonist irbesartan and MSCs could enhance efficacy in addressing DN. Methods A commonly used method for modeling type 2 diabetic nephropathy (T2DN) was established using a high-fat diet and a single low-dose injection of STZ (35 mg/kg). The animals were divided into the following 5 groups: (1) the control group (CON), (2) the diabetic nephropathy group (DN), (3) the mesenchymal stem cells treatment group (MSCs), (4) the irbesartan treatment group (Irb), and (5) the combined administration group (MSC + Irb). MSCs (2 × 106 cells/rat) were injected every 10 days through the tail vein for a total of three injections; irbesartan (30 mg/kg/d) was administered by gavage. Additionally, the safety and homing of mesenchymal stem cells were verified using positron emission tomography (PET) imaging. Results The combination treatment significantly reduced the UACR, kidney index, IGPTT, HOMA-IR, BUN, serum creatine, and related inflammatory factor levels and significantly improved renal function parameters and the expression of proteins related to glomerular podocyte injury in rats. Moreover, MSCs can homing target to damaged kidneys. Conclusions Compared to the administration of MSCs or irbesartan alone, the combination of MSCs and irbesartan exerted better protective effects on glomerular podocyte injury, providing new ideas for the clinical application of mesenchymal stem cells.

Abstract Background Aberrant activation of macrophages is associated with pathogenesis of acute lung injury (ALI). However, the potential pathogenesis has not been explored. Objectives We aimed to identify whether histone deacetylase (HDAC) 10 is involved in lipopolysaccharide (LPS)-exposed ALI and reveal the underlying pathogenesis by which it promotes lung inflammation in LPS-exposed ALI via modifying P62 with deacetylation. Methods We constructed an ALI mice model stimulated with LPS to determine the positive effect of Hdac10 deficiency. Moreover, we cultured murine alveolar macrophage cell line (MH-S cells) and primary bone marrow-derived macrophages (BMDMs) to explore the pro-inflammatory activity and mechanism of HDAC10 after LPS challenge. Results HDAC10 expression was increased both in mice lung tissues and macrophage cell lines and promoted inflammatory cytokines production exposed to LPS. Hdac10 deficiency inhibited autophagy and inflammatory response after LPS stimulation. In vivo, Hdac10 fl/fl -LysMCre mice considerably attenuated lung inflammation and inflammatory cytokines release exposed to LPS. Mechanistically, HDAC10 interacts with P62 and mediates P62 deacetylation at lysine 165 (K165), by which it promotes P62 expression and increases inflammatory cytokines production. Importantly, we identified that Salvianolic acid B (SAB), an HDAC10 inhibitor, reduces lung inflammatory response in LPS-stimulated ALI. Conclusion These results uncover a previously unknown role for HDAC10 in regulating P62 deacetylation and aggravating lung inflammation in LPS-induced ALI, implicating that targeting HDAC10 is an effective therapy for LPS-exposed ALI.

Abstract Background Increasing attention is being paid to the environmental and health impacts of nanoplastics (NPs) pollution. Exposure to nanoplastics (NPs) with different charges and functional groups may have different adverse effects after ingestion by organisms, yet the potential ramifications on mammalian blood glucose levels, and the risk of diabetes remain unexplored. Results Mice were exposed to PS-NPs/COOH/NH2 at a dose of 5 mg/kg/day for nine weeks, either alone or in a T2DM model. The findings demonstrated that exposure to PS-NPs modified by different functional groups caused a notable rise in fasting blood glucose (FBG) levels, glucose intolerance, and insulin resistance in a mouse model of T2DM. Exposure to PS-NPs-NH2 alone can also lead the above effects to a certain degree. PS-NPs exposure could induce glycogen accumulation and hepatocellular edema, as well as injury to the pancreas. Comparing the effect of different functional groups or charges on T2DM, the PS-NPs-NH2 group exhibited the most significant FBG elevation, glycogen accumulation, and insulin resistance. The phosphorylation of AKT and FoxO1 was found to be inhibited by PS-NPs exposure. Treatment with SC79, the selective AKT activator was shown to effectively rescue this process and attenuate T2DM like lesions. Conclusions Exposure to PS-NPs with different functional groups (charges) induced T2DM-like lesions. Amino-modified PS-NPs cause more serious T2DM-like lesions than pristine PS-NPs or carboxyl functionalized PS-NPs. The underlying mechanisms involved the inhibition of P-AKT/P-FoxO1. This study highlights the potential risk of NPs pollution on T2DM, and provides a new perspective for evaluating the impact of plastics aging.

BackgroundPrenatal anxiety and depression exert a significant influence on the physiological and psychological health outcomes of both expectant mothers and their infants. The aim of this study was to explore the intrinsic relationships between maternal anxiety, depression in early pregnancy, and their influencing factors. The findings of this study provide scientific basis for developing targeted preventive interventions.MethodsThe study involved 887 expectant mothers in the early stages of pregnancy residing in Changsha City from March to August 2022. The sociodemographic characteristics, health and lifestyle factors, and pregnancy-related factors of participants were collected. The Edinburgh Postnatal Depression Scale and the Self-Rating Anxiety Scale were used to assess depression and anxiety, respectively. Chi-square tests and multivariate logistic regression models using SPSS 26.0 were used to assess factors impacting early pregnancy anxiety and depression. Amos 23.0 was used to construct a path model to determine the potential pathways of the influencing factors.ResultsIn early pregnancy, the prevalence of depression and anxiety were 17.4% and 15.8%, respectively. Path analysis showed that early pregnancy anxiety and illness during pregnancy had a direct effect on early pregnancy depression. Anxiety had the greatest overall impact on early pregnancy depression. Education, maternal comorbidities, symptoms of pregnancy, electronic device usage time, work stress, active smoking in the 6 months before pregnancy, and sleep quality were found to solely exert indirect effects on early pregnancy depression. Sleep quality had the greatest overall impact on early pregnancy anxiety. Active smoking in the 6 months before pregnancy, sleep quality, and work stress only had a direct impact on early pregnancy anxiety. Additionally, electronic device usage duration and monthly per capita household income exclusively indirectly impacted symptoms of early pregnancy anxiety.ConclusionThe study highlights the importance of targeted interventions in early screening. Avoiding excessive use of electronic devices and active smoking in the 6 months before pregnancy, alleviating work stress and symptoms of pregnancy, increasing education levels and monthly per capita household income, improving sleep quality, and actively preventing illnesses during pregnancy and maternal comorbidities might reduce anxiety and depression in early pregnancy.

Abstract Natural killer T cell lymphoma (NKTCL) is highly aggressive, with advanced stage patients poorly responding to intensive chemotherapy. To explore effective and safe treatment for newly diagnosed advanced stage NKTCL, we conducted a phase II study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab (NCT04096690). Twenty-two patients with a median age of 51 years (range, 24–74) were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days, followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 days. The complete response and overall response rate after induction treatment were 59% (95%CI, 43–79%) and 68% (95%CI, 47–84%), respectively. With a median follow-up of 30 months, the 2 year progression-free and overall survival rates were 68% (95%CI, 45–83%) and 86% (95%CI, 63–95%), respectively. The most frequently grade 3/4 adverse events were neutropenia (32%, n = 7) and hypofibrinogenemia (18%, n = 4), which were manageable and led to no discontinuation of treatment. Tumor proportion score of PD-L1, peripheral blood high-density lipoprotein cholesterol, and apolipoprotein A-I correlated with good response, while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab treatment. In conclusion, the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed, advanced stage NKTCL. Dysregulated lipid profile and immunosuppressive signature contributed to treatment resistance, providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

Landslides are catastrophic geological events that can cause significant damage to properties and result in the loss of human lives. Deep-learning technology applied to optical remote sensing images can enable effective landslide-prone area detection. However, conventional landslide detection (LD) models often employ complex structural designs to ensure detection accuracy. The complexity often hampers the detection speed, rendering these models inadequate for the swift emergency monitoring of landslides. To address these problems, we propose a new lightweight deep-learning-based framework, BisDeNet, for efficient LD. To improve the efficiency of the proposed BisDeNet, we replaced the context path in the original BiSeNet with DenseNet due to its strong feature extraction ability, few required parameters, and low model complexity. Two sites with different and representative landslide developments were selected as the study areas to verify the performance of our proposed BisDeNet. Additionally, we introduced landslide causative factors to enhance the sampling dataset. To evaluate the effectiveness of our approach, we compared the performance of our BisDeNet with the performances of three other BiSeNet-based methods and an advanced transformer-based model data-efficient image transformer (DeiT). Our experimental results indicate that the F1-scores of BisDeNet in the two study areas are 0.9006 and 0.8850, which are 26.22% and 1.86% higher than the scores of BiSeNet, respectively, but slightly lower than that of the DeiT model. Furthermore, our proposed BisDeNet requires the fewest number of parameters and the least memory out of the five models.

Background This research investigates the metabolic profiles of follicular fluid (FF) samples from patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilisation and aims to identify diagnostic and therapeutic biomarkers for PCOS through lipidomic analysis.Methods We performed non-targeted lipid analysis of FF samples from women with PCOS (n = 6) and normal controls (n = 6) using ultra-high-performance liquid chromatography–tandem mass spectrometry. Differential lipids between the two groups were screened using multidimensional statistical analysis, followed by fold change analysis and t-tests to identify potential PCOS biomarkers.Results Multivariate statistical analysis revealed significant differences in FF lipid levels between the PCOS and control groups. Five different lipids were selected as standards, with p

Microplastics and phthalates are prevalent and emerging pollutants that pose a potential impact on human health. Previous studies suggest that both microplastics and phthalates can adversely affect the reproductive systems of humans and mammals. However, the combined impact of these pollutants on the female reproductive system remains unclear. Here we show the impacts of exposure to polystyrene microplastics (PS-MPs) and di-2-ethylhexyl phthalate (DEHP) on female Sprague-Dawley rats’ reproductive systems. We find that co-exposure to PS-MPs and DEHP results in a marked increase in cystic and atretic follicles, oxidative stress, fibrosis, and dysregulation of serum sex hormone homeostasis in the ovaries of the rats. Proteomic analysis identified differentially expressed proteins that were predominantly enriched in signaling pathways related to fatty acid metabolism and tight junctions, regulated by transforming growth factor β1 (TGF-β1). We further confirm that co-exposure to DEHP and PS-MPs activates the TGF-β1/Smad3 signaling pathway, and inhibiting this pathway alleviates oxidative stress, hormonal dysregulation, and ovarian fibrosis. These results indicate that exposure to the combination of microplastics and phthalates leads to a significant increase in atretic follicles and may increase the risk of polycystic ovary syndrome (PCOS). Our study provides new insights into the reproductive toxicity effects of microplastics and DEHP exposure on female mammals, highlighting the potential link between environmental pollutants and the occurrence of PCOS. These findings highlight the need for comprehensive assessments of the reproductive health risks posed by microplastic pollution to women and contribute to the scientific basis for evaluating such risks.

Background: Glioma (GBM) is the most prevalent malignancy worldwide with high morbidity and mortality. Exosome-mediated transfer of long noncoding RNA (lncRNA) has been reported to be associated with human cancers, containing GBM. Meanwhile, myeloid-derived suppressor cells (MDSCs) play a vital role in mediating the immunosuppressive environments in GBM. Objectives: This study is designed to explore the role and mechanism of exosomal (Exo) lncRNA AGAP2-AS1 on the MDSC pathway in GBM. Methods: AGAP2-AS1, microRNA-486-3p (miR-486-3p), and Transforming growth factor beta-1 (TGF-β1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, migration, and invasion were detected by 5-ethynyl-2′-deoxyuridine (EdU), flow cytometry, and Transwell assays. E-cadherin, Vimentin, CD9, CD81, and TGF-β1 protein levels were examined using Western blot. Exosomes were detected by a transmission electron microscope (TEM). Binding between miR-486-3p and AGAP2-AS1 or TGF-β1 was predicted by LncBase or TargetScan and then verified using a dual-luciferase reporter assay. Results: AGAP2-AS1 was highly expressed in GBM tissues and cells. Functionally, AGAP2-AS1 absence or TGF-β1 knockdown repressed tumor cell growth and metastasis. Furthermore, Exo-AGAP2-AS1 from GBM cells regulated TGF-β1 expression via sponging miR-486-3p in MDSCs. Exo-AGAP2-AS1 upregulation facilitated GBM cell growth and metastasis via the MDSC pathway. Conclusion: Exo-AGAP2-AS1 boosted GBM cell development partly by regulating the MDSC pathway, hinting at a promising therapeutic target for GBM treatment.

Obesity has a profound impact on metabolic health thereby adversely affecting brain structure and function. However, the majority of previous studies used a single structural index to investigate the link between brain structure and body mass index (BMI), which hinders our understanding of structural covariance between regions in obesity. This study aimed to examine the relationship between macroscale cortical organization and BMI using novel morphometric similarity networks (MSNs). The individual MSNs were first constructed from individual eight multimodal cortical morphometric features between brain regions. Then the relationship between BMI and MSNs within the discovery sample of 434 participants was assessed. The key findings were further validated in an independent sample of 192 participants. We observed that the lateral non-reward orbitofrontal cortex (lOFC) exhibited decoupling (i.e., reduction in integration) in obesity, which was mainly manifested by its decoupling with the cognitive systems (i.e., DMN and FPN) while the medial reward orbitofrontal cortex (mOFC) showed de-differentiation (i.e., decrease in distinctiveness) in obesity, which was mainly represented by its de-differentiation with the cognitive and attention systems (i.e., DMN and VAN). Additionally, the lOFC showed de-differentiation with the visual system in obesity, while the mOFC showed decoupling with the visual system and hyper-coupling with the sensory-motor system in obesity. As an important first step in revealing the role of underlying structural covariance in body mass variability, the present study presents a novel mechanism that underlies the reward-control interaction imbalance in obesity, thus can inform future weight-management approaches.

Abstract Dysregulation of IL-17A is closely associated with airway inflammation and remodeling in severe asthma. However, the molecular mechanisms by which IL-17A is regulated remain unclear. Here we identify epithelial sirtuin 6 (SIRT6) as an epigenetic regulator that governs IL-17A pathogenicity in severe asthma. Mice with airway epithelial cell-specific deletion of Sirt6 are protected against allergen-induced airway inflammation and remodeling via inhibiting IL-17A-mediated inflammatory chemokines and mesenchymal reprogramming. Mechanistically, SIRT6 directly interacts with RORγt and mediates RORγt deacetylation at lysine 192 via its PPXY motifs. SIRT6 promotes RORγt recruitment to the IL-17A gene promoter and enhances its transcription. In severe asthma patients, high expression of SIRT6 positively correlates with airway remodeling and disease severity. SIRT6 inhibitor (OSS_128167) treatment significantly attenuates airway inflammation and remodeling in mice. Collectively, these results uncover a function for SIRT6 in regulating IL-17A pathogenicity in severe asthma, implicating SIRT6 as a potential therapeutic target for severe asthma.

Background: Renal fibrosis is the main cause of the development of diabetic kidney disease (DKD). ACSL1 plays an important role in colon cancer and liver fibrosis. Methods: We screened ACSL1 by proteomics analysis and then verified the expression of ACSL1 in the urine of diabetic nephropathy patients by WB and ELISA. Then, a total of 12 db/m and db/db mice were used to verify the association between renal fibrosis and ACSL1. Periodic acid-Schiff (PAS) staining, Masson staining, and immunostaining were performed for histological studies. The relationship between ACSL1 and renal fibrosis was studied by knocking down ACSL1 in cell experiments. Results: The expression of ACSL1 was significantly increased in the exfoliated urine cells and urine supernatant of diabetic nephropathy patients and was closely related to renal function. In addition, the expression of ACSL1 was significantly increased in the renal tissues of db/db mice with fibrosis. Knocking down ACSL1 in HK-2 cells was shown to reverse renal fibrosis induced by high glucose. Conclusions: We found a potential therapeutic target for preventing or ameliorating the progression of DKD fibrosis. Reducing ACSL1 expression may be a new strategy for the treatment of renal fibrosis caused by DKD, which provides an experimental theoretical basis for new drug research. Resumen: Antecedentes: La fibrosis renal es la causa principal de desarrollo de nefropatía diabética (ND). ACSL1 juega un papel importante en el cáncer de colon y la fibrosis hepática. Métodos: Cribamos ACSL1 mediante análisis proteómico, verificando seguidamente la expresión de ACSL1 en la orina de los pacientes con nefropatía diabética mediante WB y ELISA. A continuación, utilizamos un total de 12 ratones db/m y db/db para verificar la asociación entre fibrosis renal y ACSL1. Se realizaron tinciones PAS (Periodic acid-Schiff), de Masson e inmunotinción para los estudios histológicos. Estudiamos la relación entre ACSL1 y fibrosis renal aplicando la técnica de knockdown a ACSL1 en los experimentos celulares. Resultados: La expresión de ACSL1 se incrementó significativamente en las células de orina exfoliada y el sobrenadante de orina de los pacientes con nefropatía diabética y estuvo estrechamente relacionada con la función renal. Además, la expresión de ACSL1 se incrementó significativamente en los tejidos renales de los ratones db/db con fibrosis. La realización de knockdown a ACSL1 en las células HK-2 reflejó una reversión de la fibrosis renal inducida por la alta tasa de glucosa. Conclusiones: Encontramos un objetivo terapéutico potencial para prevenir o mejorar la progresión de la fibrosis en la ND. Reducir la expresión de ACSL1 puede suponer una nueva estrategia para el tratamiento de la fibrosis renal causada por la ND, lo cual aporta una base teórica experimental para la investigación de un nuevo fármaco.

The geostationary earth orbit (GEO) represents a distinctive geosynchronous orbit situated in the Earth’s equatorial plane, providing an excellent platform for long-term monitoring of ionospheric total electron content (TEC) at a quasi-invariant ionospheric pierce point (IPP). With GEO satellites having limited dual-frequency coverage, the inclined geosynchronous orbit (IGSO) emerges as a valuable resource for ionospheric modeling across a broad range of latitudes. This article evaluates satellite differential code biases (DCB) of BDS high-orbit satellites (GEO and IGSO) and assesses regional ionospheric modeling utilizing data from international GNSS services through a refined polynomial method. Results from a 48-day observation period show a stability of approximately 2.0 ns in BDS satellite DCBs across various frequency signals, correlating with the available GNSS stations and satellites. A comparative analysis between GEO and IGSO satellites in BDS2 and BDS3 reveals no significant systematic bias in satellite DCB estimations. Furthermore, high-orbit BDS satellites exhibit considerable potential for promptly detecting high-resolution fluctuations in vertical TECs compared to conventional geomagnetic activity indicators like Kp or Dst. This research also offers valuable insights into ionospheric responses over mid-latitude regions during the March 2024 geomagnetic storm, utilizing TEC estimates derived from BDS GEO and IGSO satellites.

The switch machine, an essential element of railway infrastructure, is crucial in maintaining the safety of railway operations. Traditional methods for fault diagnosis are constrained by their dependence on extensive labeled datasets. Semi-supervised learning (SSL), although a promising solution to the scarcity of samples, faces challenges such as the imbalance of pseudo-labels and inadequate data representation. In response, this paper presents the Semi-Supervised Adaptive Matrix Machine (SAMM) model, designed for the fault diagnosis of switch machine. SAMM amalgamates semi-supervised learning with adaptive technologies, leveraging adaptive low-rank regularizer to discern the fundamental links between the rows and columns of matrix data and applying adaptive penalty items to correct imbalances across sample categories. This model methodically enlarges its labeled dataset using probabilistic outputs and semi-supervised, automatically adjusting parameters to accommodate diverse data distributions and structural nuances. The SAMM model’s optimization process employs the alternating direction method of multipliers (ADMM) to identify solutions efficiently. Experimental evidence from a dataset containing current signals from switch machines indicates that SAMM outperforms existing baseline models, demonstrating its exceptional status diagnostic capabilities in situations where labeled samples are scarce. Consequently, SAMM offers an innovative and effective approach to semi-supervised classification tasks involving matrix data.

The ski-related novel gene (SnoN), encoded by the SKIL gene, has been shown to negatively regulated transforming growth factor-β1 (TGF-β1) signaling pathway. However, the roles of SnoN in hepatic stellate cell (HSC) activation and hepatic fibrosis (HF) are still unclear. To evaluate the role of SnoN in HF, we combined bulk RNA sequencing analysis and single-cell RNA sequencing analysis to analyse patients with HF. The role of SKIL/SnoN was verified using liver samples from rat model transfected HSC-T6 and LX-2 cell lines. Immunohistochemistry, immunofluorescence, PCR, and western blotting techniques were used to demonstrate the expression of SnoN and its regulatory effects on TGF-β1 signaling in fibrotic liver tissues and cells. Furthermore, we constructed competitive endogenous RNA regulatory network and potential drug network associated with the SnoN gene. We identified SKIL gene as a differentially expressed gene in hepatic fibrosis. SnoN protein was found to be widely expressed in the cytoplasm of normal hepatic tissues, whereas it was almost absent in HF tissues. In the rat group subjected to bile duct ligation (BDL), SnoN protein expression decreased, while TGF-β1, collagen III, tissue inhibitor of metalloproteinase 1 (TIMP-1), and fibronectin levels increased. We observed the interaction of SnoN with p-SMAD2 and p-SMAD3 in the cytoplasm. Following SnoN overexpression, apoptosis of HSCs was promoted, and the expression of HF-associated proteins, including collagen I, collagen III, and TIMP-1, was reduced. Conversely, downregulation of SnoN inhibited HSC apoptosis, increased collagen III and TIMP-1 levels, and decreased matrix metalloproteinase 13 (MMP-13) expression. In conclusion, SnoN expression is downregulated in fibrotic livers, and could attenuate TGF-β1/SMADs signaling-dependent de-repression of collagen synthesis.

Background This study aims to evaluate the long-term trend of prevalence and DALY (disability-adjusted life-year) rate on the age, period and cohort (APC) of the BRICS (Brazil, Russia, India, China and South Africa) country for autoimmune diseases (rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS) and psoriasis).Methods The data are sourced from the Global Burden of Disease Study 2019, and it uses the Joinpoint regression model to estimate the time trends of autoimmune diseases from 1990 to 2019. Additionally, it employs the Age-Period-Cohort (APC) model to estimate the age, period, and cohort effects from 1990 to 2019.Results For 1990 to 2019, the ASPR (age-standardised prevalence rate) of IBD increased significantly for China and South Africa, and decreased significantly for Brazil, India, Russian. The Russian ASPR of MS demonstrated a significantly decreasing trend (average annual percent change=−0.5%, 95% CI −0.6 to −0.5), with the most increased occurring in Brazil at 2009–2014. The cohort effect on DALY rates for Psoriasis displayed an ongoing decreasing trend from the 1929–1933 birth cohort to the 1999–2003 birth cohort. Specifically, the five countries relative risk values (RRs) of DALYs due to RA increased significantly by 7.98, 16.07, 5.98, 3.19, 9.13 times, from 20 to 24 age group to 65 to 69 age group.Conclusions The population of the BRICS countries accounts for more than 40% of the global population. And we found that the age effect of various autoimmune diseases is heavily influenced by population ageing.

Research has shown that long-chain noncoding RNAs (lncRNAs) are involved in the regulation of a variety of biological processes, including peripheral nerve regeneration, in part by acting as competing endogenous RNAs. c-Jun plays a key role in the repair of peripheral nerve injury. However, the precise underlying mechanism of c-Jun remains unclear. In this study, we performed microarray and bioinformatics analysis of mouse crush-injured sciatic nerves and found that the lncRNA Pvt1 was overexpressed in Schwann cells after peripheral nerve injury. Mechanistic studies revealed that Pvt1 increased c-Jun expression through sponging miRNA-214. We overexpressed Pvt1 in Schwann cells cultured in vitro and found that the proliferation and migration of Schwann cells were enhanced, and overexpression of miRNA-214 counteracted the effects of Pvt1 overexpression on Schwann cell proliferation and migration. We conducted in vivo analyses and injected Schwann cells overexpressing Pvt1 into injured sciatic nerves of mice. Schwann cells overexpressing Pvt1 enhanced the regeneration of injured sciatic nerves following peripheral nerve injury and the locomotor function of mice was improved. Our findings reveal the role of lncRNAs in the repair of peripheral nerve injury and highlight lncRNA Pvt1 as a novel potential treatment target for peripheral nerve injury.

Background: Gynecological malignancies, such as endometrial cancer (EC) and uterine cancer are prevalent. Increased Acyl-CoA synthetase long-chain family member 1 (ACSL1) activity may contribute to aberrant lipid metabolism, which is a potential factor that contributes to the pathogenesis of endometrial cancer. This study aimed to elucidate the potential molecular mechanisms by which ACSL1 is involved in lipid metabolism in endometrial cancer, providing valuable insights for targeted therapeutic strategies. Methods: Xenograft mouse models were used to assess the effect of ACSL1 on the regulation of endometrial cancer progression. ACSL1 protein levels were assessed via immunohistochemistry and immunoblotting analysis. To assess the migratory potential of Ishikawa cells, wound-healing and Transwell invasion assays were performed. Changes in lipids in serum samples from mice with endometrial cancer xenotransplants were examined in an untargeted lipidomic study that combined multivariate statistical methods with liquid chromatography‒mass spectrometry (LC/MS). Results: Patient sample and tissue microarray data suggested that higher ACSL1 expression is strongly associated with the malignant progression of EC. Overexpression of ACSL1 enhances fatty acid β-oxidation and 5′-adenylate triphosphate (ATP) generation in EC cells, promoting cell proliferation and migration. Lipidomic analysis revealed that significant changes were induced by ACSL1, including changes to 28 subclasses of lipids and a total of 24,332 distinct lipids that were detected in both positive and negative ion modes. Moreover, pathway analysis revealed the predominant association of these lipid modifications with the AMPK/CPT1C/ATP pathway and fatty acid β-oxidation. Conclusions: This study indicates that ACSL1 regulates the AMPK/CPT1C/ATP pathway, which induces fatty acid β-oxidation, promotes proliferation and migration, and then leads to the malignant progression of EC.

Depression is a highly prevalent disorder of the central nervous system. The neuropsychiatric symptoms of clinical depression are persistent and include fatigue, anorexia, weight loss, altered sleep patterns, hyperalgesia, melancholia, anxiety, and impaired social behaviours. Mounting evidences suggest that neuroinflammation triggers dysregulated cellular immunity and increases susceptibility to psychiatric diseases. Neuroimmune responses have transformed the clinical approach to depression because of their roles in its pathophysiology and their therapeutic potential. In particular, activated regulatory T (Treg) cells play an increasingly evident role in the inflammatory immune response. In this review, we summarized the available data and discussed in depth the fundamental roles of Tregs in the pathogenesis of depression, as well as the clinical therapeutic potential of Tregs. We aimed to provide recent information regarding the potential of Tregs as immune-modulating biologics for the treatment and prevention of long-term neuropsychiatric symptoms of depression.

Abstract Background To date, the influence of Roussouly type on development of adjacent segment degeneration (ASD) after lumber fusion is still not fully explored, and the current study is aimed to evaluate the effect of Roussouly type on development of radiological ASD after single-level lumber fusion, and to compare the Roussouly types and spinopelvic parameters among those with different degenerative patterns of ASDs on sagittal plane. Methods A retrospective review of 288 patients underwent L4/5 or L5/S1 single-level posterior interbody fusions between January 2016 and December 2018 with a minimum 2-year follow up was performed. Radiological ASDs were identified and divided into 3 groups according to different degenerative patterns of the cephalad adjacent level on sagittal plane, including the types of retrolisthesis (Group A), anterolisthesis (Group B), and axial disc space narrowing (Group C). Roussouly types and radiological measurements were compared among three groups and potential risk factors for ASD were evaluated. Results Radiological ASD was found in 59 (20.5%) cases, in which patients with Roussouly type-2 was the most common. While, on subgroup analysis among three ASD groups, Roussouly type-1 occupied the highest proportion in Group A, differ in Group B and Group C, both with Type-2 as the most common. Moreover, Group A had significantly lower pelvic tilt (PT), larger sacral slope (SS), and larger segmental angle (SA) than Group B and Group C, which showed a more anteverted pelvic in Group A. Multivariate regression analysis noted Roussouly type, preoperative PT, and ∆PI-LL as the independent risk factors for radiological ASD. Conclusion Roussouly type was significantly associated with the development of radiological ASD; however, the Roussouly types and spinal pelvic parameters were varied among different sagittal degenerative patterns of ASD, which was important in restoring optimal lumbar sagittal alignments in initial surgery.

ABSTRACT: This study was designed to depict prevalence and antimicrobial resistance characteristics of Proteus mirabilis (P. mirabilis) strains in 4 chicken farms and to probe the transfer mechanism of resistance genes. A total of 187 P. mirabilis isolates were isolated from 4 chicken farms. The susceptibility testing of these isolates to 14 antimicrobials showed that the multidrug resistance (MDR) rate was as high as 100%. The β-lactamase resistance genes blaOXA-1, blaCTX-M-1G, blaCTX-M-9G and colistin resistance gene mcr-1 were highly carried in the P. mirabilis isolates. An MDR strain W47 was selected for whole genome sequencing (WGS) and conjugation experiment. The results showed that W47 carried 23 resistance genes and 64 virulence genes, and an SXT/R391 integrated conjugative elements (ICEs) named ICEPmiChn5 carrying 17 genes was identified in chromosome. ICEPmiChn5 was able to be excised from the chromosome of W47 forming a circular intermediate, but repeated conjugation experiments were unsuccessful. Among 187 P. mirabilis isolates, 144 (77.01%, 144/187) isolates carried ICEPmiChn5-like ICEs, suggesting that ICEs may be the major vector for the transmission of resistance genes among MDR chicken P. mirabilis strains in this study. The findings were conducive to insight into the resistance mechanism of chicken P. mirabilis strains and provide a theoretical basis for the use of antibiotics for the treatment of MDR P. mirabilis infections in veterinary clinic.

Summary: Neurons require large amounts of energy, but whether they can perform glycolysis or require glycolysis to maintain energy remains unclear. Using metabolomics, we show that human neurons do metabolize glucose through glycolysis and can rely on glycolysis to supply tricarboxylic acid (TCA) cycle metabolites. To investigate the requirement for glycolysis, we generated mice with postnatal deletion of either the dominant neuronal glucose transporter (GLUT3cKO) or the neuronal-enriched pyruvate kinase isoform (PKM1cKO) in CA1 and other hippocampal neurons. GLUT3cKO and PKM1cKO mice show age-dependent learning and memory deficits. Hyperpolarized magnetic resonance spectroscopic (MRS) imaging shows that female PKM1cKO mice have increased pyruvate-to-lactate conversion, whereas female GLUT3cKO mice have decreased conversion, body weight, and brain volume. GLUT3KO neurons also have decreased cytosolic glucose and ATP at nerve terminals, with spatial genomics and metabolomics revealing compensatory changes in mitochondrial bioenergetics and galactose metabolism. Therefore, neurons metabolize glucose through glycolysis in vivo and require glycolysis for normal function.

Background: Several studies performed thus far indicate that neuroinflammation may be one of the mechanisms underlying the pathogenesis of neuropathic pain (NP). Autophagy, as an adaptive response, has been regarded as an active process of removing the inflammatory stimulus and restoring homeostatic balance. Resolution of inflammation is a biochemical process mediated by the so-called aspirin-triggered specialized proresolving lipid mediators (AT-SPMs), which are thought to exert protective effects in NP. Recent studies have proposed mechanisms in models of inflammatory disorders and showed a relationship between resolution of inflammation and autophagy. This study aimed to validate the functional effects of Aspirin-triggered Resolvin D1 (AT-RvD1) on in vitro and in vivo models of inflammation and to determine their roles in the regulation of autophagy and activation of the Nod-like receptor protein 3 (NLRP3) inflammasome signaling pathway.Methods: An NP model was established using L5-6 spinal nerve ligation (SNL) and a model of tumor necrosis factor alpha (TNF-α)-stimulated primary microglia was established to evaluate the effect of SPMs. Western blotting was used to detect the level of NLRP3 inflammasomes complexes proteins (NLRP3, ASC, and Caspase-1) and autophagy-related proteins (LC3B, and Beclin1). Immunofluorescence staining was used to understand the autophagy and NLRP3 inflammasome activation process. The behavioral changes in rats were analyzed using paw withdrawal thresholds (PWT) and paw withdrawal latency (PWL) test.Results: Our results showed that AT-SPMs significantly upregulated the activation of autophagy, which was characterized by an increase in the ratio of LC3B-II/I and accumulation of ATG5 and Beclin1. AT-RvD1 showed a dose-dependent decrease in the upregulated PWT and PWL induced by SNL and suppressed the expression of the NLRP3 inflammasome protein and the production of its corresponding downstream proinflammatory factors. Additionally, AT-RvD1 induced the activation of autophagy of the microglia and decreased the expression of the NLRP3 inflammasome protein and the accumulation of proinflammatory factors in TNF-ɑ-challenged microglia.Conclusion: Thus, these results showed that AT-RvD1 may be a potential alternative therapeutic strategy for the prevention or treatment of NP by inhibition of the NLRP3 inflammasome signaling pathway by targeting the induction of autophagy.

Abstract Nanomaterials are promising carriers to improve the bioavailability and therapeutic efficiency of drugs by providing preferential drug accumulation at their sites of action, but their delivery efficacy is severely limited by a series of biological barriers, especially the mononuclear phagocytic system (MPS)—the first and major barrier encountered by systemically administered nanomaterials. Herein, the current strategies for evading the MPS clearance of nanomaterials are summarized. First, engineering nanomaterials methods including surface modification, cell hitchhiking, and physiological environment modulation to reduce the MPS clearance are explored. Second, MPS disabling methods including MPS blockade, suppression of macrophage phagocytosis, and macrophages depletion are examined. Last, challenges and opportunities in this field are further discussed.

Bacteria can facilitate the increase of Mg2+ content in biotic aragonite, but the molecular mechanisms of the incorporation of Mg2+ ion into aragonite facilitated by bacteria are still unclear and the dolomitization of aragonite grains is rarely reported. In our laboratory experiments, the content of Mg2+ ions in biotic aragonite is higher than that in inorganically-precipitated aragonite and we hypothesize that the higher Mg content may enhance the subsequent dolomitization of aragonite. In this study, biotic aragonite was induced by Bacillus licheniformis Y1 at different Mg/Ca molar ratios. XRD data show that only aragonite was precipitated in the media with Mg/Ca molar ratios at 6, 9, and 12 after culturing for 25 days. The EDS and atomic absorption results show that the content of Mg2+ ions in biotic aragonite increased with rising Mg/Ca molar ratios. In addition, our analyses show that the EPS from the bacteria and the organics extracted from the interior of the biotic aragonite contain the same biomolecules, including Ala, Gly, Glu and hexadecanoic acid. The content of Mg2+ ions in the aragonite precipitates mediated by biomolecules is significantly higher than that in inorganically-precipitated aragonite. Additionally, compared with Ala and Gly, the increase of the Mg2+ ions content in aragonite promoted by Glu and hexadecanoic acid is more significant. The DFT (density functional theory) calculations reveal that the energy needed for Mg2+ ion incorporation into aragonite mediated by Glu, hexadecanoic acid, Gly and Ala increased gradually, but was lower than that without acidic biomolecules. The experiments also show that the Mg2+ ion content in the aragonite significantly increased with the increasing concentration of biomolecules. In a medium with high Mg2+ concentration and with bacteria, after 2 months, micron-sized dolomite rhombs were precipitated on the surfaces of the aragonite particles. This study may provide new insights into the important role played by biomolecules in the incorporation of the Mg2+ ions into aragonite. Moreover, these experiments may contribute towards our understanding of the dolomitization of aragonite in the presence of bacteria.

Objective: To prepare adipose-derived stem cells (ADSCs)-embedded alginate-gelatinemicrospheres (Alg-Gel-ADSCs MSs) by electrospray and evaluate their feasibility for cartilage tissue engineering. To observe the efficacy of Alg-Gel-ADSCs MSs in repairing articular cartilage defects in SD rats. Methods: ADSCs were isolated and characterized by performing induced differentiation and flow cytometry assays. Alginate-gelatine microspheres with different gelatine concentrations were manufactured by electrospraying, and the appropriate alginate-gelatine concentration and ratio were determined by evaluating microsphere formation. Alg-Gel-ADSCs MSs were compared with Alg-ADSCs MSs through the induction of chondrogenic differentiation and culture. Their feasibility for cartilage tissue engineering was analysed by performing Live/Dead staining, cell proliferation analysis, toluidine blue staining and a glycosaminoglycan (GAG) content analysis. Alg-Gel-ADSCs MSs were implanted in the cartilage defects of SD rats, and the cartilage repair effect was evaluated at different time points. The evaluation included gross observations and histological evaluations, fluorescence imaging tracking, immunohistochemical staining, microcomputed tomography (micro-CT) and a CatWalk evaluation. Results: The isolated ADSCs showed multidirectional differentiation and were used for cartilage tissue engineering. Using 1.5 w:v% alginate and 0.5 w:v% gelatine (Type B), we successfully prepared nearly spherical microspheres. Compared with alginate microspheres, alginate gel increased the viability of ADSCs and promoted the proliferation and chondrogenesis of ADSCs. In our experiments on knee cartilage defects in SD rats in vivo, the Alg-Gel-ADSCs MSs showed superior cartilage repair in cell resides, histology evaluation, micro-CT imaging and gait analysis. Conclusions: Microspheres composed of 1.5 w:v% alginate-0.5 w:v% gelatine increase the viability of ADSCs and supported their proliferation and deposition of cartilage matrix components. ADSCs embedded in 1.5 w:v% alginate-0.5 w:v% gelatine microspheres show superior repair efficacy and prospective applications in cartilage tissue repair. The translational potential of this article: In this study, injectable adipose-derived stem cells-embedded alginate-gelatin microspheres (Alg-Gel-ADSCs MSs) were prepared by the electrospray . Compared with the traditional alginate microspheres, its support ability for ADSCs is better and shows a better repair effect. This study provides a promising strategy for cartilage tissue regeneration.

The extensive use of carrier-aided smoothing code (CSC) filters has led to a reduction in the noise level of raw code measurements in GNSS positioning and navigation applications. However, the existing CSC technique is sensitive to the changes in the integer ambiguity, and then the smoothing procedure needs to be restarted in the presence of cycle slips. As the Doppler shift is instantaneously observed and immune to cycle slips, the Doppler-aided smoothing code (DSC) algorithm would be more promising in a challenged environment. Based on the Hatch filter, an optimal DSC approach is proposed with the principle of minimum variance. Meanwhile, to inhibit the effect of the integral cumulative error of the Doppler, a balance factor is adopted to adjust the contributions of raw code and DSC. The noise level of code observable is not only affected by thermal noise, but also limited by systematic bias. Satellite code bias (SCB) was identified in the raw code observable on each frequency for each BDS-2 satellite. By minimizing the sum of the absolute value of residuals, the polynomial segment fitting algorithm as a function of elevation angles is applied to establish the SCB correction model based on epoch-differenced multipath (MP) deviations. Finally, different types of experiments demonstrate the validity and efficiency of the refined DSC filter with SCB corrections on each available frequency for BDS un-GEO satellites.

Abstract Endogenous clocks generate rhythms in gene expression, which facilitates the organisms to cope through periodic environmental variations in accordance with 24-h light/dark time. A core question that needs to be elucidated is how such rhythms proliferate throughout the cells and regulate the dynamic physiology. In this study, we demonstrate the role of REGγ as a new regulator of circadian clock in mice, primary MEF, and SY5Y cells. Assessment of circadian conduct reveals a difference in circadian period, wheel mode, and the ability to acclimate the external light stimulus between WT and KO littermates. Compared to WT mice, REGγ KO mice attain the phase delay behavior upon light shock at early night. During the variation of 12/12 h light/dark (LD) exposure, levels of Per1, Per2, Cry1, Clock, Bmal1, and Rorα circadian genes in suprachiasmatic nucleus are significantly higher in REGγ KO than in WT mice, concomitant with remarkable changes in BMAL1 and PER2 proteins. In cultured cells depleted of REGγ, serum shock induces early response of the circadian genes Per1 and Per2 with the cyclic rhythm maintained. Mechanistic study indicates that REGγ directly degrades BMAL1 by the non-canonical proteasome pathway independent of ATP and ubiquitin. Silencing BMAL1 abrogates the changes in circadian genes in REGγ-deficient cells. However, inhibition of GSK-3β, a known promoter for degradation of BMAL1, exacerbates the action of REGγ depletion. In conclusion, our findings define REGγ as a new factor, which functions as a rheostat of circadian rhythms to mitigate the levels of Per1 and Per2 via proteasome-dependent degradation of BMAL1.

Robots are expected to execute various operation tasks like a human by learning human working skills, especially for complex contact tasks. Increasing demands for human–robot interaction during task execution makes robot motion planning and control a considerable challenge, not only to reproduce demonstration motion and force in the contact space but also to resume working after interacting with a human without re-planning motion. In this article, we propose a novel framework based on a time-invariant dynamical system (DS), taking into account both human skills transfer and human–robot interaction. In the proposed framework, the human demonstration trajectory was modeled by the pose diffeomorphic DS to achieve online motion planning. Furthermore, the motion of the DS was modified by admittance control to satisfy different demands. We evaluated the method with a UR5e robot in the contact task of the composite woven layup. The experimental results show that our approach can effectively reproduce the trajectory and force learned from human demonstration, allow human–robot interaction safely during the task, and control the robot to return to work automatically after human interaction.

Abstract Exosomes participate in intercellular communication and glioma microenvironment modulation, but the exact mechanisms by which glioma-derived exosomes (GDEs) promote the generation of the immunosuppressive microenvironment are still unclear. Here, we investigated the effects of GDEs on autophagy, the polarization of tumor-associated macrophages (TAMs), and glioma progression. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) markedly facilitated autophagy and M2-like macrophage polarization, which subsequently promoted glioma proliferation and migration in vitro and in vivo. Western blot and qRT-PCR analyses indicated that interleukin 6 (IL-6) and miR-155-3p were highly expressed in H-GDEs. Further experiments showed that IL-6 and miR-155-3p induced M2-like macrophage polarization via the IL-6-pSTAT3-miR-155-3p-autophagy-pSTAT3 positive feedback loop, which promotes glioma progression. Our study clarifies a mechanism by which hypoxia and glioma influence autophagy and M2-like macrophage polarization via exosomes, which could advance the formation of the immunosuppressive microenvironment. Our findings suggest that IL-6 and miR-155-3p may be novel biomarkers for diagnosing glioma and that treatments targeting autophagy and the STAT3 pathway may contribute to antitumor immunotherapy.

Background: Neuronal- and circuit-level abnormalities of excitation and inhibition are shown to be associated with tau and amyloid-beta (Aβ) in preclinical models of Alzheimer’s disease (AD). These relationships remain poorly understood in patients with AD. Methods: Using empirical spectra from magnetoencephalography and computational modeling (neural mass model), we examined excitatory and inhibitory parameters of neuronal subpopulations and investigated their specific associations to regional tau and Aβ, measured by positron emission tomography, in patients with AD. Results: Patients with AD showed abnormal excitatory and inhibitory time-constants and neural gains compared to age-matched controls. Increased excitatory time-constants distinctly correlated with higher tau depositions while increased inhibitory time-constants distinctly correlated with higher Aβ depositions. Conclusions: Our results provide critical insights about potential mechanistic links between abnormal neural oscillations and cellular correlates of impaired excitatory and inhibitory synaptic functions associated with tau and Aβ in patients with AD. Funding: This study was supported by the National Institutes of Health grants: K08AG058749 (KGR), F32AG050434-01A1 (KGR), K23 AG038357 (KAV), P50 AG023501, P01 AG19724 (BLM), P50-AG023501 (BLM and GDR), R01 AG045611 (GDR); AG034570, AG062542 (WJ); NS100440 (SSN), DC176960 (SSN), DC017091 (SSN), AG062196 (SSN); a grant from John Douglas French Alzheimer’s Foundation (KAV); grants from Larry L. Hillblom Foundation: 2015-A-034-FEL (KGR), 2019-A-013-SUP (KGR); grants from the Alzheimer’s Association: AARG-21-849773 (KGR); PCTRB-13-288476 (KAV), and made possible by Part the CloudTM (ETAC-09-133596); a grant from Tau Consortium (GDR and WJJ), and a gift from the S. D. Bechtel Jr. Foundation.

The recognition and mapping of landslide (RML) is an important task in hazard and risk research and can provide a scientific basis for the prevention and control of landslide disasters. However, traditional RML methods are inefficient, costly, and not intuitive. With the rapid development of computer vision, methods based on convolutional neural networks have attracted great attention due to their numerous advantages. However, problems such as insufficient feature extraction, excessive parameters, and slow model testing have restricted the development of this technology. This research proposes a new RML framework based on a new semantic segmentation network termed the fully convolutional DenseNet (FC-DenseNet). In this network, the features extracted from each layer are repeatedly used in a dense connection, and the parameters are controlled by a bottle-neck structure. Meanwhile, the structure of the encoder-decoder solves the problem of the slowness of model testing. Finally, the landslide influencing factors are added, which enriches the training data. To verify the effectiveness of the proposed method, we focused on several deep networks for comparison and analysis. The results show that FC-DenseNet can better recognize the boundary and interior of landslides, and there are fewer missing and excessive recognition results. The kappa value of the new method is 94.72% in Site 1, which is 6% and 4% higher than that of U-Net and ResU-Net, respectively, and 94.56% in Site 2, which is 6% and 3% higher than that of U-Net and ResU-Net, respectively, indicating that FC-DenseNet has great potential in RML applications.

ObjectiveStress is a major public health challenge and is associated with undesirable eating behavior. This cross-sectional study aimed to explore whether there is an association between perceived level of stress and food preference among Chinese adults.Study DesignPerceived level of stress was measured using the Chinese version of the 14-item Perceived Stress Scale, whereas self-reported food preferences were investigated by means of five food classification questions, including questions regarding the consumption of fast food, salty snacks, fruit, vegetables, and soft/sugary drinks.MethodsThe data were collected from the 2015 China Health and Nutrition Survey. Information of 8,216 adults (≥18 years) on perceived level of stress, self-reported food preferences, and other important covariates was available and analyzed.ResultsPerceived level of stress was negatively associated with a preference for fruit (β = −0.58, 95% CI: −0.81 to −0.34, p < 0.0001) and vegetables (β = −1.13, 95% CI: −1.41 to −0.85, p < 0.0001), while it was positively associated with a preference for fast food (β = 0.36, 95% CI: 0.08–0.64, p = 0.011) and soft/sugary drinks (β = 0.48, 95% CI: 0.30–0.66, p < 0.0001) after adjusting for potential confounders. No association between a preference for salty snacks and perceived level of stress was found in either men or women.ConclusionsThe present population-based study reported strong associations between perceived level of stress and self-reported food preferences among Chinese adults. Sex differences related to this association were also worthy of attention.

We aimed to examine the association between serum cotinine and leukocyte telomere length (LTL) and the intermediate effects of body mass index (BMI) and C-reactive protein (CRP) on modulating the association. This study included 4,047 adults from the 1999 to 2002 National Health and Nutrition Examination Survey. In the combined sample, after adjusting for age, race, sex, physical activity, and alcohol use, the total effect of serum cotinine on LTL was significant (standardized regression coefficient, β = −0.049, p = 0.001) without BMI and CRP included in the model. With inclusion of BMI but without CRP in the model, the direct effect of cotinine on LTL in its absolute value increased to β = −0.053 (p < 0.001), and the suppression effect of BMI was estimated at 8.8%. With inclusion of CRP but without BMI in the model, the direct effect of cotinine on LTL in its absolute value decreased to β = −0.040 (p = 0.008), and the mediation effect of CRP was estimated at 16.9%. With inclusion of both BMI and CRP in the model, BMI and CRP still had significant suppression and mediation effects, respectively, on the cotinine-LTL association. These findings suggest that weight and inflammation have different roles in the inverse association between serum cotinine and LTL.

Objective The objective of this study was to investigate the net micromineral (Cu, Fe, Mn, Zn) requirements for maintenance and growth of Dorper×Jinzhong crossbred ewe lambs at their latter fattening period. Methods Thirty 1/2 Dorper × 1/2 Jinzhong crossed F1 ewe lambs (35±0.5 kg of body weight [BW]) were used and divided into five groups in a randomized design for a comparative slaughter trial. At the beginning of the experiment, six lambs were randomly selected and slaughtered at 35 kg BW to determine their initial body composition. When their BWs reached 43 kg, another six lambs fed ad libitum were slaughtered to serve as an intermediate slaughter group. The retained eighteen lambs were randomly distributed into three groups and offered one type of feed at 100%, 65%, and 40% of the ad libitum intake. When the lambs fed ad libitum reached a BW of 50 kg, the three groups were slaughtered. The body composition (muscle, fat, bone, blood with viscera, skin, and wool) were weighted, ground, mixed, and subsampled for mineral content analysis. Results The net maintenance requirements of Cu, Fe, Mn, and Zn were 0.017, 0.160, 0.004, and 0.067 mg/kg BW/d, respectively, and the net growth requirements per 100 grams of average daily gain ranged from 0.48 to 0.51 mg of Cu, 2.63 to 2.17 mg of Fe, 0.12 to 0.15 mg of Mn, and 2.07 to 2.00 mg of Zn, respectively, for Dorper × Jinzhong crossed ewes from 35 to 50 kg BW. Conclusion Our results suggest that the micromineral requirements for both maintenance and growth of Dorper × Jinzhong crossbred ewe lambs were quite different from the recommendations of NRC (2007), except for Zn.

How the REGγ-proteasome pathway is regulated during the cell cycle or genotoxic insults remains unclear. Here, the authors show that NIP30 acts as a molecular switch to regulate the REGγ-proteasome activity and may provide an approach to combat drug-resistant tumours lacking functional p53.

Abstract Background Based on previous theoretical oral-health-related quality of life (OHRQoL) models and most recently framework, as well as sociocultural model of body image dissatisfaction, the current study aimed to investigate the effect of individual (dental aesthetics and dental appearance social comparison) and sociocultural factors (social reinforcement from parents, peers and mass media on dental aesthetics) as well as their interaction on psychosocial dimension of OHRQoL among adolescent orthodontic patients. Methods In this cross-sectional study comprising 427 adolescent orthodontic patients (151 boys and 276 girls) aged between 11 and 16 years old, the psychosocial dimension of OHRQoL was measured by Psychosocial Impact of Dental Aesthetics Questionnaire. Individual predictor of dental aesthetics was defined by the Aesthetic Component of the Index of Orthodontic Treatment Need, and dental appearance social comparison was assessed by four items adapted from Physical Appearance Comparison Scale. Sociocultural predictor of social reinforcement was measured by six items adapted from Perceived Sociocultural Pressure Scale. Spearman correlations, path analyses, and structural equation modeling were used to build up several predictive models. Results As hypothesized, two direct pathways were observed that patients’ dental aesthetics and all three sources of social reinforcement directly predicted the psychosocial dimension of OHRQoL. Meanwhile, we observed one indirect pathway, that three sources of social reinforcement predicted the psychosocial dimension of OHRQoL, in part, through dental appearance social comparison. Conclusions This study provides preliminary evidence indicating that dental aesthetics, social reinforcement and dental appearance comparison are reliable predictors of psychosocial dimension of OHRQoL among adolescent orthodontic patients.

Gliomas are the most common primary malignant tumours of the central nervous system, and new molecular biomarkers are urgently needed for diagnosis and targeted therapy. Here, we report that increased beta‐site APP‐cleaving enzyme 2 (BACE2) expression is associated with increases in the grade of human glioma, the incidence of the mesenchymal molecular glioblastoma multiforme subtype and the likelihood of poor prognoses for patients. BACE2 knockdown suppressed cell invasion, cell migration and tumour growth both in vitro and in vivo, while BACE2 overexpression promoted the mesenchymal transition and cell proliferation. Furthermore, TGFβ1 stimulated BACE2 expression through Smad‐dependent signalling, which modulated TNF‐α‐induced NF‐κB activity through the PP1A/IKK pathway to promote tumorigenesis in both U87MG and U251 cells. Our study indicated that BACE2 plays a significant role in glioma development. Therefore, BACE2 is a potential therapeutic target for human gliomas due to its function and ability to be regulated.

Abstract Background The first few weeks after childbirth are critical, as women may encounter lactation problems and postpartum depression during this period. However, it is still unclear whether early breastfeeding behaviours are related to the symptoms of postnatal depression (PND) in Chinese populations. Therefore, the current study aimed to investigate the association between symptoms of PND and infant feeding practices based on a large-scale Chinese cohort. Methods A prospective study of the community-based cohort was conducted from January 2015 to December 2016. Infant feeding outcomes, including exclusive/partial breastfeeding and formula feeding, were assessed according to the WHO guidelines. Symptoms of PND were assessed by the Edinburgh Postnatal Depression Scale at 4 weeks postpartum. Multivariate generalized estimating equation models were applied to investigate the associations between depressive symptoms and infant feeding behaviours. Results A total of 956 mother-infant pairs were included. Fifty-six mothers presented screen-positive symptoms of PND with a cut-off ≥10. The percentage of early breastfeeding initiation was 75.8%, while the average duration of exclusive breastfeeding was 3.90 ± 2.33 months. Postnatal depressive symptoms were associated with a shorter breastfeeding duration (8.02 vs. 6.32 months, P

Alterations in the peripheral (e.g., serum, plasma, platelet) concentrations of arginine and its related catabolic products (i.e., ornithine, citrulline) in the urea and nitric oxide cycles have been reported to be associated with major depressive disorder (MDD). The meta-analysis herein aimed to explore the association between the concentration of peripheral arginine, its catabolic products and MDD, as well as to discuss the possible role of arginine catabolism in the onset and progression of MDD. PubMed, EMBASE, PsycINFO and Web of Science were searched from inception to June 2020. The protocol for the meta-analysis herein has been registered at the Open Science Framework [https://doi.org/10.17605/osf.io/7fn59]. In total, 745 (47.5%) subjects with MDD and 823 (52.5%) healthy controls (HCs) from 13 articles with 16 studies were included. Fifteen of the included studies assessed concentrations of peripheral arginine, eight assessed concentrations of ornithine, and six assessed concentrations of citrulline. Results indicated that: (1) the concentrations of arginine, ornithine, and citrulline were not significantly different between individuals with MDD and HCs when serum, plasma and platelet are analyzed together, (2) in the subgroups of serum samples, the concentrations of arginine were lower in individuals with MDD than HCs, and (3) concurrent administration of psychotropic medications may be a confounding variable affecting the concentrations of arginine, ornithine, and citrulline. Our findings herein do not support the hypothesis that arginine catabolism between individuals with MDD and HCs are significantly different. The medication status and sample types should be considered as a key future research avenue for assessing arginine catabolism in MDD.

Abstract Effective delivery of anticancer drugs into the nucleus for pharmacological action is impeded by a series of intratumoral transport barriers. Despite the significant potential of magnetic nanovehicles in electromagnetic field (EF)‐activated drug delivery, modularizing a tandem magnetoresponsive activity in a one‐nanoparticle system to meet different requirements at both tissue and cellular levels remain highly challenging. Herein, a strategy is described by employing sequential EF frequencies in inducing a succession of magnetoresponses in the magnetic nanovehicles that aims to realize cascaded tissue penetration and nuclear accumulation. This nanovehicle features ferrimagnetic vortex‐domain iron oxide nanorings coated with a thermo‐responsive polyethylenimine copolymer (PI/FVIOs). It is shown that the programmed cascading of low frequency (Lf)‐EF‐induced magnetophoresis and medium frequency (Mf)‐EF‐stimulated magneto‐thermia can steer the Doxorubicin (DOX)‐PI/FVIOs to the deep tissue and subsequently trigger intracellular burst release of DOX for successful nuclear entry. By programming the order of different EF frequencies, it is demonstrated that first‐stage Lf‐EF and subsequent Mf‐EF operation enables DOX‐PI/FVIOs to effectively deliver 86.2% drug into the nucleus in vivo. This nanodelivery system empowers potent antitumoral activity in various models of intractable tumors, including DOX‐resistant MCF‐7 breast cancer cells, triple‐negative MDA‐MB‐231 breast cancer cells, and BxPC‐3 pancreatic cancer cells with poor permeability.

Psychological stress is a negative affective state. The association between physical activity and psychological stress was commonly reported in previous researches. Few published studies with large sample sizes have explored such an association in Chinese population. The current research aims to assess the association between perceived stress and physical activity preferences, as well as the association between risk of high perceived stress and physical activity behaviors (e.g., sports-, transport-, occupational-related physical activity, sedentary activities and time in bed). The data were collected from the China Health and Nutrition Survey (CHNS) in 2015. Generalized linear models and logistic regression models were used to explore the association between perceived stress and physical activity. In total, 11,066 participants were included in the current analysis. For physical activity preferences, we found that “like” preference of all six mentioned domains of activities contributed to lower perceived stress (i.e., lower perceived stress scale −14 score, all β < 0 and p < 0.05). For physical activity behaviors, the results indicated that none/low intensity physical activity behaviors (e.g., sports-, occupational- related, sedentary) were associated with risk of high perceived stress, except that low intensity of transport-related activities seemed to be protective from high stress. However, the association between intensity of physical activity behaviors and perceived stress was not simply the higher the better. High intensity of all these physical activity behaviors was also associated with high perceived stress. Our findings suggest that positive preferences and moderate physical activity behaviors were associated with low perceived stress. The findings herein highlight the effect of regulating physical activity on perceived stress, as well as inform potential strategies to reduce psychological stress.

Spectral analysis based on neural field theory is used to analyze dynamic connectivity via methods based on the physical eigenmodes that are the building blocks of brain dynamics. These approaches integrate over space instead of averaging over time and thereby greatly reduce or remove the temporal averaging effects, windowing artifacts, and noise at fine spatial scales that have bedeviled the analysis of dynamical functional connectivity (FC). The dependences of FC on dynamics at various timescales, and on windowing, are clarified and the results are demonstrated on simple test cases, demonstrating how modes provide directly interpretable insights that can be related to brain structure and function. It is shown that FC is dynamic even when the brain structure and effective connectivity are fixed, and that the observed patterns of FC are dominated by relatively few eigenmodes. Common artifacts introduced by statistical analyses that do not incorporate the physical nature of the brain are discussed and it is shown that these are avoided by spectral analysis using eigenmodes. Unlike most published artificially discretized “resting state networks” and other statistically-derived patterns, eigenmodes overlap, with every mode extending across the whole brain and every region participating in every mode—just like the vibrations that give rise to notes of a musical instrument. Despite this, modes are independent and do not interact in the linear limit. It is argued that for many purposes the intrinsic limitations of covariance-based FC instead favor the alternative of tracking eigenmode coefficients vs. time, which provide a compact representation that is directly related to biophysical brain dynamics.

The morphology, crystal structure, and elemental composition of biominerals are commonly different from chemically synthesized minerals, but the reasons for these are not fully understood. A facultative anaerobic bacterium, Enterobacter ludwigii SYB1, is used in experiments to document the hydrochemistry, mineral crystallization, and cell surface characteristics of biomineralization. It was found that carbonate anhydrase and ammonia production were major factors influencing the alkalinity and saturation of the closed biosystem. X-ray diffraction (XRD) spectra showed that calcite, monohydrocalcite (MHC), and dypingite formed in samples with bacterial cells. It was also found that the (222) plane of MHC was the preferred orientation compared to standard data. Scanning transmission electron microscopy (STEM) analysis of cell slices provides direct evidence of concentrated calcium and magnesium ions on the surface of extracellular polymeric substances (EPS). In addition, high-resolution transmission electron microscopy (HRTEM) showed that crystallized nanoparticles were formed within the EPS. Thus, the mechanism of the biomineralization induced by E. ludwigii SYB1 can be divided into three stages: (i) the production of carbonate anhydrase and ammonia increases the alkalinity and saturation state of the milieu, (ii) free calcium and magnesium ions are adsorbed and chelated onto EPS, and (iii) nanominerals crystallize and grow within the EPS. Seventeen kinds of amino acids were identified within both biotic MHC and the EPS of SYB1, while the percentages of glutamic and aspartic acid in MHC increased significantly (p < 0.05). Furthermore, the adsorption energy was calculated for various amino acids on seven diffracted crystal faces, with preferential adsorption demonstrated on (111) and (222) faces. At the same time, the lowest adsorption energy was always that of glutamic and aspartic acid for the same crystal plane. These results suggest that aspartic and glutamic acid always mix preferentially in the crystal lattice of MHC and that differential adsorption of amino acids on crystal planes can lead to their preferred orientation. Moreover, the mixing of amino acids in the mineral structure may also have a certain influence on the mineral lattice dislocations, thus enhancing the thermodynamic characteristics.

Modern people live in an environment with ubiquitous food cues, including food advertisements, videos, and smells. Do these food cues change people’s eating behavior? Since diet plays a crucial role in maintaining health, it has been researched for decades. As convenient alternatives for real food, food images are widely used in diet research. To date, researchers from Germany, Spain, and other countries have established food photo databases; however, these food pictures are not completely suitable for Chinese studies because of the ingredients and characteristics of Chinese food. The main goal of this research is to create a library of Chinese food images and to provide as complete a data reference as possible for future studies that use food images as experimental material. After standardized processing, we selected 508 common Chinese food pictures with high familiarity and recognizability and attached detailed classifications concerning taste, macronutrients, calories, and participants’ emotional responses to the pictures. Additionally, with food pictures as material, we conducted research on how people make dietary decisions in order to identify the variables that may affect a person’s food choices. The effects of individual perceived healthiness and palatability, gender, BMI, family income, and levels of emotional and restricted eating were examined using eating decisions based on healthiness and palatability as dependent variables. The results showed that people with low household incomes are more likely to be influenced by food taste in their dietary decision-making process, while individuals with high household incomes are more likely to consider the healthy aspects of food. Moreover, parental BMI affects what children consume, with children who have parents with higher BMIs being more prone to overlook the healthiness value of food.

Summary: Development of spermatogonia and spermatocytes are the critical steps of spermatogenesis, impacting on male fertility. Investigation of the related regulators benefits the understanding of male reproduction. The proteasome system has been reported to regulate spermatogenesis, but the mechanisms and key contributing factors in vivo are poorly explored. Here we found that ablation of REGγ, a proteasome activator, resulted in male subfertility. Analysis of the mouse testes after birth showed there was a decreased number of PLZF+ spermatogonia and spermatocytes. Molecular analysis found that REGγ loss significantly increased the abundance of p53 protein in the testis, and directly repressed PLZF transcription in cell lines. Of note, allelic p53 haplodeficiency partially rescued the defects in spermatogenesis observed in REGγ-deficient mice. In summary, our results identify REGγ-p53-PLZF to be a critical pathway that regulates spermatogenesis and establishes a new molecular link between the proteasome system and male reproduction. : In this article, Lei Li and colleagues show that ablation of REGγ, a proteasome activator, resulted in male subfertility, partially because of a decreased number of PLZF+ spermatogonia and spermatocytes. Mechanistically, REGγ loss significantly increased the abundance of p53 protein, and transcriptionally represses PLZF expression. Allelic p53 haplodeficiency partially rescued the defects in spermatogenesis observed in REGγ-deficient mice. Keywords: REGγ, PLZF, p53, spermatogonial stem cells, mouse reproduction