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Abstract Background Bipolar disorder (BPD) is a kind of manic and depressive phase alternate episodes of serious mental illness, and it is correlated with well-documented cortical brain abnormalities. Emerging evidence supports that autophagy dysfunction in neuronal system contributes to pathophysiological changes in neurological disease. However, the role of autophagy in bipolar disorder has rarely been elucidated. This study aimed to identify the autophagy-related gene as a potential biomarker Correlated to immune infiltration in BPD. Methods The microarray dataset GSE23848 and autophagy-related genes (ARGs) were downloaded. Differentially expressed genes (DEGs) between normal and BPD samples were screened using the R software. Machine learning algorithms were performed to screen the significant candidate biomarker from autophagy-related differentially expressed genes (ARDEGs). The correlation between the screened ARDEGs and infiltrating immune cells was explored through correlation analysis. Results In this study, the autophagy pathway was abundantly enriched and activated in BPD, as indicated by Pathway enrichment analysis. We identified 16 ARDEGs in BPD compared to the normal group. A signature of 4 ARDEGs (ERN1, ATG3, CTSB, and EIF2AK3) was screened. ROC analysis showed that the above genes have good diagnostic performance. In addition, immune correlation analysis considered that the above four genes significantly correlated with immune cells in BPD. Conclusions Autophagy - immune cell axis mediates pathophysiological changes in BPD. Four important ARDEGs are prospective to be potential biomarkers associated with immune infiltration in BPD and helpful for the prediction or diagnosis of BPD.

ABSTRACTBackground: Previous research has indicated that continuous exposure to disaster-related information through social media can lead to vicarious trauma. However, scholars have recognized the need for further in-depth research into the underlying mechanisms influencing this relationship.Objective: The purpose of this study is to investigate the impact mechanism of social media usage on vicarious traumatization in users and analyze the roles of recommendation systems and peer communication.Methods: This study was conducted with college students in China, focusing on the context of the MU5735 aircraft flight accident in China in which 123 passengers and 9 crew members died. Data were collected through an online questionnaire. The partial least square structural equation modelling (PLS-SEM) method was used to test the data and model.Results: This study obtained valid responses from 1317 participants. The study findings revealed a significant positive correlation between social media usage(β = 0.180，P

1’-Hydroxy-4’,8,8’-trimethoxy-[2,2’-binaphthalene]-1,4-dione (compound 5), a secondary metabolite recently discovered in marine fungi, demonstrates promising cytotoxic and anticancer potential. However, knowledge regarding the anticancer activities and biological mechanisms of its derivatives remains limited. Herein, a series of novel naphthoquinone-naphthol derivatives were designed, synthesised, and evaluated for their anticancer activity against cancer cells of different origins. Among these, Compound 13, featuring an oxopropyl group at the ortho-position of quinone group, exhibited the most potent inhibitory effects on HCT116, PC9, and A549 cells, with IC50 values decreasing from 5.27 to 1.18 μM (4.5-fold increase), 6.98 to 0.57 μM (12-fold increase), and 5.88 to 2.25 μM (2.6-fold increase), respectively, compared to compound 5. Further mechanistic studies revealed that compound 13 significantly induced cell apoptosis by increasing the expression levels of cleaved caspase-3 and reducing Bcl-2 proteins through downregulating the EGFR/PI3K/Akt signalling pathway, leading to the inhibition of proliferation in HCT116 and PC9 cells. The present findings suggest this novel naphthoquinone-naphthol derivative may hold potential as an anticancer therapeutic lead.

Perivascular adipose tissue (PVAT) is a unique fat depot surrounding blood vessels and plays a vital role in the progression of vascular remodeling and dysfunction. PVAT exhibits remarkable differences in structure, phenotype, origin, and secretome across anatomical locations. The proximity of PVAT to neighboring vascular beds favors a niche for bidirectional communication between adipocytes and vascular smooth muscle cells, endothelial cells, and immune cells. In this review, we update our understanding of PVAT’s regional differences and provide a comprehensive exploration of how these differences impact cross-talks between PVAT and the vascular wall. Different PVAT depots show different degrees of vasoprotective function and resilience to pathological changes such as obesity and vasculopathies, shaping multifaceted interactions between PVAT depots and adjacent vasculatures. The depot-specific resilience may lead to innovative strategies to manage cardiometabolic disorders.

Tigecycline is a last-resort drug used to treat serious infections caused by multidrug-resistant bacteria. tet(X4) is a recently discovered plasmid-mediated tigecycline resistance gene that confers high-level resistance to tigecycline and other tetracyclines. Since the first discovery of tet(X4) in 2019, it has spread rapidly worldwide, and as a consequence, tigecycline has become increasingly ineffective in the clinical treatment of multidrug-resistant infections. In this study, we identified and analyzed tet(X4)-positive Escherichia coli isolates from duck farms in Hunan Province, China. In total, 976 samples were collected from nine duck farms. Antimicrobial susceptibility testing and whole-genome sequencing (WGS) were performed to establish the phenotypes and genotypes of tet(X4)-positive isolates. In addition, the genomic characteristics and transferability of tet(X4) were determined based on bioinformatics analysis and conjugation. We accordingly detected an E. coli strain harboring tet(X4) and seven other resistance genes in duck feces. Multi-locus sequence typing analysis revealed that this isolate belonged to a new clone, and subsequent genetic analysis indicated that tet(X4) was carried in a 4608-bp circular intermediate, flanked by ISVsa3-ORF2-abh elements. Moreover, it exhibited transferability to E. coli C600 with a frequency of 10-5. The detection of tet(X4)-harboring E, coli strains on duck farms enhances our understanding of tigecycline resistance dynamics. The transferable nature of the circular intermediate of tet(X4) contributing to the spread of tigecycline resistance genes poses a substantial threat to healthcare. Consequently, vigilant monitoring and proactive measures are necessary to prevent their spread.

BackgroundObservational studies suggest an association between telomere length (TL) and blood lipid (BL) levels. Nevertheless, the causal connections between these two traits remain unclear. We aimed to elucidate whether genetically predicted TL is associated with BL levels via Mendelian randomization (MR) and vice versa.MethodsWe obtained genetic instruments associated with TL, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) from large-scale genome-wide association studies (GWASs). The causal relationships between TL and BL were investigated via bidirectional MR, multivariable MR and mediation analysis methods. The inverse variance weighted (IVW) method was employed as the principal methodology, complemented by several other estimators to enhance the robustness of the analysis.ResultsIn the forward MR analyses, we identified significant positive correlation between genetically predicted TL and the levels of TG (β=0.04, 95% confidence interval [CI]: 0.01 to 0.06, p = 0.003). In the reverse MR analysis, TG (β=0.02, 95% CI: 0.01 to 0.03, p = 0.004), LDL-C (β=0.03, 95% CI: 0.01 to 0.04, p = 0.001) and ApoB (β=0.03, 95% CI: 0.01 to 0.04, p = 9.71×10–5) were significantly positively associated with TL, although this relationship was not observed in the multivariate MR analysis. The mediation analysis via two-step MR showed no significant mediation effects acting through obesity-related phenotypes in analysis of TL with TG, while the effect of LDL-C on TL was partially mediated by body mass index (BMI) in the reverse direction, with mediated proportion of 12.83% (95% CI: 0.62% to 25.04%).ConclusionsOur study indicated that longer TL were associated with higher TG levels, while conversely, higher TG, LDL-C, and ApoB levels predicted longer TL, with BMI partially mediating these effects. Our findings present valuable insights into the development of preventive strategies and interventions that specifically target TL-related aging and age-related diseases.

Abstract Copper is an essential micronutrient that plays a pivotal role in numerous physiological processes in virtually all cell types. Nevertheless, the dysregulation of copper homeostasis, whether towards excess or deficiency, can lead to pathological alterations, such as atherosclerosis. With the advent of the concept of copper-induced cell death, termed cuproptosis, researchers have increasingly focused on the potential role of copper dyshomeostasis in atherosclerosis. In this review, we provide a broad overview of cellular and systemic copper metabolism. We then summarize the evidence linking copper dyshomeostasis to atherosclerosis and elucidate the potential mechanisms underlying atherosclerosis development in terms of both copper excess and copper deficiency. Furthermore, we discuss the evidence for and mechanisms of cuproptosis, discuss its interactions with other modes of cell death, and highlight the role of cuproptosis-related mitochondrial dysfunction in atherosclerosis. Finally, we explore the therapeutic strategy of targeting this novel form of cell death, aiming to provide some insights for the management of atherosclerosis.

Abstract Background Cervical cancer is strongly associated with human papillomavirus (HPV) infection. In this retrospective study, we analyzed the data of postmenopausal women who were tested for HPV in Nanjing First Hospital from 2019 to 2021. Methods We retrospectively analyzed the data of 14,608 postmenopausal women aged 45–90 years, who underwent HPV examination in Nanjing First Hospital between January 2019 and December 2021. All participants were tested for 23 HPV genotypes. We subsequently analyzed the infection rate and evaluated the distribution of HPV using the chi-square test. Results Our results showed that the HPV infection rate in postmenopausal women in Nanjing, China was 22.36%. In terms of age group, the infection rate was 19.54%, 24.30%, 26.58%, and 14.99% in those aged ≤ 50, 51–60, 61–70, and ≥ 71 years, respectively. The most common HPV subtypes were HPV52 (22.1 3%), HPV58 (15.86%), HPV53 (14.17%), HPV16 (12.61%), and HPV81 (11.66%), in that order. The single-HPV infection rate was 14.23%, and the multiple-genotype infection rate was 8.14% (1189/14,608). Conclusions This study showed that in Nanjing, China, the different age groups of post-menopausal women could have different rates of HPV infection, and the most common types were HPV52, HPV58, HPV53, HPV16 and HPV81. These findings highlighted the importance of understanding the epidemiology of HPV infection in specific populations, such as postmenopausal women in Nanjing, China. The results could provide valuable information for healthcare professionals and policymakers to develop targeted prevention and screening strategies for reducing the burden of HPV-related diseases in this population.

Chronic obstructive pulmonary disease (COPD) kills more than 3 million people worldwide every year. Despite progress in the treatment of symptoms and prevention of acute exacerbations, few advances have been made to ameliorate disease progression or affect mortality. Exercise plays a positive role in the prevention and treatment of diaphragm dysfunction in COPD, and the changes in diaphragm structure and function induced by exercise are closely related to the regulation of oxidative stress. But the mechanism remains unclear. So the aim of this study was to reveal the therapeutic mechanism of exercise to COPD using both in vivo and in vitro experiments. In this study, cigarette smoke (CS) induced COPD mice model, treadmill aerobic training for COPD mice were constructed and cigarette smoke extract (CSE) induced bronchial epithelial cells (BECs) model were used for COPD study. Bioinformatics analysis, luciferase reporting analysis, and RT-qPCR detection were used to clarify the interacted relationship among lncRNA, miRNA, and mRNA. ROS, inflammatory cytokines expression, and EMT relative protein α-SMA were detected using immunofluorescence and ELISA detection. The result shows that exercise ameliorates COPD induced lung injury by inhibit ROS, inflammation, and epithelial-mesenchymal transition (EMT) relative protein α-SMA expression. RT-qPCR detection shows that lnc-H19 expression was increased in lung tissues of COPD mice. Exercise decreased COPD induced lnc-H19 expression. Downregulation lnc-H19 inhibits COPD mediated lung injury. Bioinformatics analysis and luciferase reporting analysis confirmed that miR-181 and PDCD4 were downstream targets of lnc-H19. Upregulation of PDCD4 or downregulation of miR-181 reversed the protective effect of si-lnc-H19 to BECs after exposure to CSE. In conclusion, lncRNA H19 contributes to smoke-related chronic obstructive pulmonary disease by targeting miR-181/PDCD4 Axis.

Abstract Immunity-and-matrix-regulatory cells (IMRCs) derived from human embryonic stem cells have unique abilities in modulating immunity and regulating the extracellular matrix, which could be mass-produced with stable biological properties. Despite resemblance to mesenchymal stem cells (MSCs) in terms of self-renew and tri-lineage differentiation, the ability of IMRCs to repair the meniscus and the underlying mechanism remains undetermined. Here, we showed that IMRCs demonstrated stronger immunomodulatory and pro-regenerative potential than umbilical cord MSCs when stimulated by synovial fluid from patients with meniscus injury. Following injection into the knees of rabbits with meniscal injury, IMRCs enhanced endogenous fibrocartilage regeneration. In the dose-escalating phase I clinical trial (NCT03839238) with eighteen patients recruited, we found that intra-articular IMRCs injection in patients was safe over 12 months post-grafting. Furthermore, the effective results of magnetic resonance imaging (MRI) of meniscus repair and knee functional scores suggested that 5 × 107 cells are optimal for meniscus injury treatment. In summary, we present the first report of a phase I clinical trial using IMRCs to treat meniscus injury. Our results demonstrated that intra-articular injection of IMRCs is a safe and effective therapy by providing a permissive niche for cartilage regeneration.

Abstract Intestinal symbiotic microorganisms have a strong capacity to regulate the physiological functions of their host, and Drosophila serves as a useful model. Enterococcus faecium (E. faecium) is a member of the normal intestinal flora of animals. Lactic acid bacteria (LAB) such as E. faecium can promote the growth and development of Drosophila, but the mechanism of regulation of Drosophila is poorly understood. In this study, we found that E. faecium used a carbon source to produce probiotic acids. E. faecium is a symbiotic bacterium for Drosophila, and adult flies passed on parental flora to offspring. E. faecium promoted the growth and development of Drosophila, especially under poor nutritional conditions. E. faecium shortened the developmental process for Drosophila and accelerated the transformation from larva to pupa. Finally, E. faecium promoted the growth and development of Drosophila through TOR and insulin signalling pathways.

Abstract Purpose Journal clubs hold significant importance in medical education, with numerous studies highlighting their contributions worldwide. However, studies specifically examining their role in China, particularly among Chinese medical postgraduates categorized into academic and clinical types, remain scarce. This research aims to investigate the participation, performance, and benefits of journal clubs, and explore the influence of student type and study phase on these aspects. Method A survey encompassing demographic information, participation rates, performance evaluations, and perceived improvements was distributed to postgraduates at Tongji Medical College of Huazhong University of Science and Technology. A total of 232 completed questionnaires were included for further analysis. Statistical analysis employed the Mann–Whitney U test and Gamma tests, with statistical significance set at p-value

Background: Exercise has been reported to be associated with a reduced risk of nonalcoholic fatty liver disease (NAFLD), but there is no consensus on the role of weight changes in this association. This study aims to investigate whether the impact of exercise on NAFLD is mainly dependent on weight changes or is inherent to exercise itself.Methods: The study recruited 1671 Chinese NAFLD-free adults in 2019, and collected their exercise habits as well as 3 years of medical examination data including anthropometric measurements, blood biochemistry parameters, and liver ultrasound results. Univariate and multivariate logistic regression models were employed to examine the impact of exercise habits on NAFLD risk, with mediation analysis utilized to estimate the magnitude of the role of weight maintenance in the association between exercise and NAFLD.Results: After adjusting for confounders, moderate to high-intensity exercisers were 1.56 times (95% CIs = 1.09–2.22) more likely to successfully control their body weight, and therefore the weight-controlled group had a lower NAFLD risk of 34.9% (95% CIs = 21.8%–56.0%) compared to the weight-gain group. Mediation analysis reveals that exercise can significantly reduce the risk of NAFLD both through weight maintenance (37.1%) and independent of weight maintenance (62.9%).Conclusion: It might be more crucial to emphasize the adoption of regular moderate to high-intensity exercise for preventing NAFLD in the general population, rather than solely focusing on weight maintenance.

Abstract. Background:. Synovectomy has been introduced into total knee arthroplasty (TKA) with the aim of relieving pain and inflammation of the synovium. However, there are no long-term, comparative data to evaluate the effect of synovectomy in TKA. This study was aimed at assessing pain, function, and complications in patients undergoing synovectomy during TKA for osteoarthritis (OA) at long-term follow-up. Methods:. This was a prospective randomized controlled trial of 42 consecutive patients who underwent staged bilateral TKA. Patients undergoing the first-side TKA were allocated to receive TKA with or without synovectomy followed by a 3-month washout period and crossover to the other strategy for the opposite-side TKA. The overall efficacy of both strategies was evaluated by determination of blood loss, the Knee Society score (KSS), and knee inflammation conditions during a 3-month postoperative period. The postoperative pain, range of motion (ROM), and complications were sequentially evaluated to compare the two groups until 10 years after surgery. Results:. At the 10-year follow-up, both groups had a similarly significantly improved ROM (114.88 ± 9.84° vs. 114.02 ± 9.43°, t = 0.221, P = 0.815) and pain relief with no differences between the two groups (1.0 [1.0] vs. 1.0 [1.5], U = 789.500, P = 0.613). Similar changes in total blood loss, KSS, and knee inflammation were found in both groups during 3 months postoperatively (P > 0.05). Additionally, there was no significant difference regarding complications and satisfaction between the two groups (P > 0.05). Conclusions:. Synovectomy in conjunction with TKA for primary OA does not seem to provide any benefit regarding postoperative pain, ROM, and satisfaction during a 10-year follow-up. In addition, it may not result in more blood loss and increased incidence of long-term complications. Based on our long-term findings, it should not be performed routinely. Trial registration:. Chinese Clinical Trial Registry, ChiCTR-INR-16008245; https://www.chictr.org.cn/showproj.aspx?proj=13334.

Multi-drug resistance of bacteria producing extended-spectrum β-lactamase (ESBL) is a public health challenge. Thus, this study aimed to investigate the antimicrobial susceptibility of ESBL-producing Escherichia coli (ESBL-EC) in Hunan Province, China. A total of 1366 fecal samples were collected from pig, chicken, and cattle farms over a six-year period, which were assessed using strain isolation, 16S rRNA identification, polymerase chain reaction, drug sensitivity testing, whole-genome sequencing, and bioinformatics analysis. The results showed an overall prevalence of 6.66% for ESBL-EC strains, with ESBL positivity extents for pigs, chickens, and cattle isolates at 6.77%, 6.54%, and 12.5%, respectively. Most ESBL-EC isolates were resistant to cefotaxime, tetracycline, and trimethoprim-sulfamethoxazole; however, all the isolates were susceptible to meropenem, with relatively low resistance to amikacin and tigecycline. Various multi-locus sequence types with different origins and similar affinities were identified, with ST155 (n = 16) being the most common subtype. Several types of resistance genes were identified among the 91 positive strains, with beta-lactamase blaCTX-M-55 being the most common ESBL genotype. IncFIB was the predominant plasmid type. Widespread use of antibiotics in animal farming may increase antibiotic resistance, posing a serious threat to the health of farmed animals and, thus, to human food security and health.

Objective Acetate plays an important role in host lipid metabolism. However, the network of acetate-regulated lipid metabolism remains unclear. Previous studies show that mitogen-activated protein kinases (MAPKs) and mechanistic target of rapamycin (mTOR) play a crucial role in lipid metabolism. We hypothesize that acetate could affect MAPKs and/or mTOR signaling and then regulate lipid metabolism. The present study investigated whether any cross talk occurs among MAPKs, mTOR and acetate in regulating lipid metabolism. Methods The ceramide C6 (an extracellular signaling-regulated kinases 1 and 2 [ERK1/2] activator) and MHY1485 (a mTOR activator) were used to treat rabbit adipose-derived stem cells (ADSCs) with or without acetate, respectively. Results It indicated that acetate (9 mM) treatment for 48 h decreased the lipid deposition in rabbit ADSCs. Acetate treatment decreased significantly phosphorylated protein levels of ERK1/2 and mTOR but significantly increased mRNA level of hormone-sensitive lipase (HSL). Acetate treatment did not significantly alter the phosphorylated protein level of p38 MAPK and c-Jun aminoterminal kinase (JNK). Activation of ERK1/2 and mTOR by respective addition in media with ceramide C6 and MHY1485 significantly attenuated decreased lipid deposition and increased HSL expression caused by acetate. Conclusion Our results suggest that ERK1/2 and mTOR signaling pathways are associated with acetate regulated HSL gene expression and lipid deposition.

BackgroundBrain atrophy represents a final common pathway for pathological processes in patients with cerebral small vessel disease (CSVD) and is now recognized as a strong independent predictor of clinical status and progression. The mechanism underlying brain atrophy in patients with CSVD is not yet fully comprehended. This study aims to investigate the association of morphologic features of intracranial distal arteries (A2, M2, P2 and more distal) with different brain structures [gray matter volume (GMV), white matter volume (WMV), and cerebrospinal fluid volume (CSFV)]. Furthermore, we also examined whether a correlation existed between these cerebrovascular characteristics and GMV in different brain regions.MethodA total of 39 participants were eventually enrolled. The morphologic features of intracranial distal arteries based on TOF-MRA were extracted and quantified using the intracranial artery feature extraction technique (iCafe). The brain 3D-T1 images were segmented into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) using the “Segment” tool in CAT12 for the voxel-based morphometry (VBM) analysis. Univariable and multivariable linear regression models were used to investigate the relationship between these cerebrovascular features and different brain structures. Partial correlation analysis with a one-tailed method was used to evaluate the relationship between these cerebrovascular features and GMV in different brain regions.ResultsOur findings indicate that both distal artery length and density were positively correlated with GM fraction in CSVD patients, regardless of whether univariable or multivariable linear regression analyses were performed. In addition, distal artery length (β = −0.428, p = 0.007) and density (β = −0.337, p = 0.036) were also found to be negative associated with CSF fraction, although this relationship disappeared after adjusting for potential confounders. Additional adjustment for the effect of WMHs volume did not change these results. In subgroup anasysis, we found that participants in the highest distal artery length tertile had significantly higher GM fraction and lower CSF fraction level than participants in the lowest distal artery length tertile. In partial correlation analysis, we also found that these cerebrovascular characteristics associated with regional GMV, especially subcortical nuclear.ConclusionThe morphologic features of intracranial distal arteries, including artery length, density and average tortuosity, measured from 3D-TOF MRA, are associated with generalized or focal atrophy indexes of CSVD.

Sleep plays an essential role in all studied animals with a nervous system. However, sleep deprivation leads to various pathological changes and neurobehavioral problems. Astrocytes are the most abundant cells in the brain and are involved in various important functions, including neurotransmitter and ion homeostasis, synaptic and neuronal modulation, and blood–brain barrier maintenance; furthermore, they are associated with numerous neurodegenerative diseases, pain, and mood disorders. Moreover, astrocytes are increasingly being recognized as vital contributors to the regulation of sleep-wake cycles, both locally and in specific neural circuits. In this review, we begin by describing the role of astrocytes in regulating sleep and circadian rhythms, focusing on: (i) neuronal activity; (ii) metabolism; (iii) the glymphatic system; (iv) neuroinflammation; and (v) astrocyte–microglia cross-talk. Moreover, we review the role of astrocytes in sleep deprivation comorbidities and sleep deprivation-related brain disorders. Finally, we discuss potential interventions targeting astrocytes to prevent or treat sleep deprivation-related brain disorders. Pursuing these questions would pave the way for a deeper understanding of the cellular and neural mechanisms underlying sleep deprivation-comorbid brain disorders.

Background: Chaihu and Longgu Muli decoction (CLMD) has been used as a classical prescription of traditional Chinese medicine (TCM) prescription to treat Parkinson's disease with depression (PDD). Nevertheless, the potential mechanisms underlying their neuroprotective effects are not well-understood. Purpose: To evaluate the neuroprotective effects and possible involvement of a molecular signaling pathway of CLMD in a PDD rat model. Methods: Adult male SD rats were randomly divided into six groups: control, model, positive (madopar 0.032 g kg−1 day−1), low dosage (L, 5 g kg−1 day−1), medium dosage (M, 10 g kg−1 day−1) and high dosage (H, 20 g kg−1 day−1) of CLMD. The neuroprotective effects of CLMD were investigated using behavioral tests, immunohistochemistry, immunofluorescence, high-performance liquid chromatography (HPLC), and Nissl staining. Western blotting was used to further investigate the mechanism of action of CLMD. The protein expression of LC3, AMPK, p-AMPK, mTOR, and p-mTOR were examined. Results: CLMD exhibited a protective effect on dopaminergic neurons by increasing the expression of tyrosine hydroxylase, which was predicted to be decreased by rotenone. CLMD restored behavior impaired by rotenone and increased the degradation of α-Syn aggregation to reduce tyrosine hydroxylase loss. Additionally, it upregulated the expression of LC3, p-AMPK/AMPK, and downregulated the expression of p-mTOR/mTOR. Conclusion: : These findings provide evidence that CLMD restored behavior performance, protected dopaminergic neurons and activated autophagy by regulating the AMPK/mTOR signaling pathway in rat model of PDD. CLMD restored behavior and protected dopaminergic neurons by regulating the AMPK/mTOR signaling pathway to induce autophagy and inhibit apoptotic activity.

Abstract Objectives To present a review on the pathogenesis, risk factor and treatment of chronic obstructive pulmonary disease complicated with osteoporosis and provide new ideas for the diagnosis and treatment. Data source A systematic search is carried out using keywords as chronic obstructive pulmonary disease, osteoporosis, risk factors, and pulmonary rehabilitation. Results Patients with chronic obstructive pulmonary disease have a high prevalence of osteoporosis and a high risk of fracture. The mechanisms of osteoporosis in COPD patients are associated with general risk factors, such as smoking, reduced physical activity, low weight, and disease‐specific risk factors, such as systemic inflammatory, Vitamin D deficiency, use of glucocorticoid, anemia, hypoxemia, and hypercapnia. The treatment of osteoporosis in COPD emphasizes comprehensive intervention, which mainly include basic treatment and anti‐osteoporosis drugs. Noticeably, pulmonary rehabilitation program is an important part of treatment. Conclusions This work summarizes the pathogenesis, risk factor, prevention, and treatment of chronic obstructive pulmonary disease complicated with osteoporosis, and the latest progress of studies on chronic obstructive pulmonary disease and osteoporosis is discussed.

Abstract Semen Ziziphi Spinosae (SZS) has been extensively used in the daily diet as a functional food for neuroprotective health-benefit in China for many years. However, the neuroprotective mechanism of SZS associated with blood–brain barrier (BBB) integrity remains unexplored. The present study suggests SZS could protect against lipopolysaccharide (LPS)-induced BBB dysfunction. Proteomics indicate that 135 proteins in rat brain are significantly altered by SZS. These differentially expressed proteins are mainly clustered into cell–cell adhesion and adherens junctions, which are closely related with BBB integrity. SZS reversed LPS-induces BBB breakdown by activating the FAK-DOCK180-Rac1-WAVE2-Arp3 pathway. Molecular docking between signaling pathway proteins and identified SZS components in rat plasma reveals that 6”‘-feruloylspinosin, spinosin, and swertisin strongly binds to signaling proteins at multiple amino acid sites. These novel findings suggest a health benefit of SZS in prevention of cerebral diseases and contributes to the further application of SZS as a functional food.

Head smut is a soil-borne fungal disease caused by Sporisorium reilianum that infects maize tassels and ears. This disease poses a tremendous threat to global maize production. A previous study found markedly different and stably heritable tassel symptoms in some maize inbred lines with Sipingtou blood after infection with S. reilianum. In the present study, 55 maize inbred lines with Sipingtou blood were inoculated with S. reilianum and classified into three tassel symptom types (A, B, and C). Three maize inbred lines representing these classes (Huangzao4, Jing7, and Chang7-2, respectively) were used as test materials to investigate the physiological mechanisms of tassel formation in infected plants. Changes in enzyme activity, hormone content, and protein expression were analyzed in all three lines after infection and in control plants. The activities of peroxidase (POD), superoxide dismutase (SOD), and phenylalanine-ammonia-lyase (PAL) were increased in the three typical inbred lines after inoculation. POD and SOD activities showed similar trends between lines, with the increase percentage peaking at the V12 stage (POD: 57.06%, 63.19%, and 70.28% increases in Huangzao4, Jing7, and Chang7-2, respectively; SOD: 27.01%, 29.62%, and 47.07% in Huangzao4, Jing7, and Chang7-2, respectively. These were all higher than in the disease-resistant inbred line Mo17 at the same growth stage); this stage was found to be key in tassel symptom formation. Levels of gibberellic acid (GA3), indole-3-acetic acid (IAA), and abscisic acid (ABA) were also altered in the three typical maize inbred lines after inoculation, with changes in GA3 and IAA contents tightly correlated with tassel symptoms after S. reilianum infection. The differentially expressed proteins A5H8G4, P09233, and Q8VXG7 were associated with changes in enzyme activity, whereas P49353, P13689, and P10979 were associated with changes in hormone contents. Fungal infection caused reactive oxygen species (ROS) and nitric oxide (NO) bursts in the three typical inbred lines. This ROS accumulation caused biofilm disruption and altered host signaling pathways, whereas NO signaling triggered strong secondary metabolic responses in the host and altered the activities of defense-related enzymes. These factors together resulted in the formation of varying tassel symptoms. Thus, interactions between S. reilianum and susceptible maize materials were influenced by a variety of signals, enzymes, hormones, and metabolic cycles, encompassing a very complex regulatory network. This study preliminarily identified the physiological mechanisms leading to differences in tassel symptoms, deepening our understanding of S. reilianum-maize interactions.

Background: Ovarian clear cell carcinoma (OCCC) is a special pathological type of epithelial ovarian cancer (EOC). Due to its low incidence rate, there is a lack of real-world studies at present. The purpose of the study is to construct a nomogram model for predicting postoperative cancer-specific survival (CSS) of patients with OCCC and analyze in detail the risk factors associated with OCCC. To construct a nomogram model for predicting postoperative CSS of patients with OCCC and analyze in detail the risk factors associated with OCCC. Methods: The clinical pathological data of 596 OCCC patients were collected from the surveillance, epidemiology, and end results (SEER) database from 2010 to 2015. Of these patients, 420 were allocated to the training group and 176 patients to the validation group using bootstrap resampling. The nomogram was developed based on the Cox regression model for predicting the cancer-specific survival probability of patients at 3 and 5 years after the operation. The model was evaluated in both the training and validation groups using consistency index, receiver operating characteristic (ROC), and calibration plots. Results: The independent risk factors for CSS in OCCC patients included International Federation of Gynecology and Obstetrics (FIGO) stage, race, age, tumor laterality, and the log odds of positive lymph nodes (LODDS). The nomograms were established for predicting the 3-year and 5-year CSS of patients after operation. The c-index of the nomogram for CSS was 0.786 in the training group and 0.742 in the verification group. Area under the curve (AUCs) of the 3-year and 5-year ROC curves were 0.818, 0.824 in the training group; and 0.816, 0.808 in the verification group, respectively. Conclusions: Based on the real population data, the construction of the CSS prediction model after OCCC surgery has high prediction efficiency, can identify postoperative high-risk OCCC patients, and can be a valuable aid for the tumor staging system.

Atherosclerosis (AS) is the main cause of cardiovascular disease (CVD) and is characterized by endothelial damage, lipid deposition, and chronic inflammation. Gut microbiota plays an important role in the occurrence and development of AS by regulating host metabolism and immunity. As human mitochondria evolved from primordial bacteria have homologous characteristics, they are attacked by microbial pathogens as target organelles, thus contributing to energy metabolism disorders, oxidative stress, and apoptosis. Therefore, mitochondria may be a key mediator of intestinal microbiota disorders and AS aggravation. Microbial metabolites, such as short-chain fatty acids, trimethylamine, hydrogen sulfide, and bile acids, also affect mitochondrial function, including mtDNA mutation, oxidative stress, and mitophagy, promoting low-grade inflammation. This further damages cellular homeostasis and the balance of innate immunity, aggravating AS. Herbal medicines and their monomers can effectively ameliorate the intestinal flora and their metabolites, improve mitochondrial function, and inhibit atherosclerotic plaques. This review focuses on the interaction between gut microbiota and mitochondria in AS and explores a therapeutic strategy for restoring mitochondrial function and intestinal microbiota disorders using herbal medicines, aiming to provide new insights for the prevention and treatment of AS.

Dragon’s blood (DB) has shown a protective effect on neurological diseases. Microgravity (MG) or simulated MG (SMG) can induce blood–brain barrier (BBB) dysfunction, which is a characteristic feature of neurological disorders. This study’s purpose was to evaluate the effect of DB on SMG-induced BBB dysfunction and explore its signaling pathway. Both DB and vitamin C (Vc) were administered orally for tail-suspended rats within 3 weeks. DB and Vc solutions were added to human brain microvascular endothelial cells (HCMEC/D3) cells, which were then exposed to SMG for 24 h. The protective effect of DB was assessed by hematoxylin and eosin and Nissl staining, ultrastructure observation, and permeability in rats. Cell apoptosis and the distribution of tight junction (TJ) and adherens junction (AJ) proteins and filamentous actin (F-actin) were examined in HCMEC/D3. The oxidative stress and inflammation, and TJ and AJ protein expressions were determined in rat brain and HCMEC/D3. The focal adhesion kinase (FAK) signaling pathway proteins were determined. DB protected SMG-induced rat BBB disruption by improving neuronal apoptosis, repairing widened intercellular space, and decreasing BBB permeability. DB effectively relieved SMG-induced HCMEC/D3 damage by inhibiting cell apoptosis and restoring F-actin spindle distribution. High doses of DB upregulated TJ and AJ protein expressions and decreased oxidative stress and proinflammatory cytokine levels in rat brain and HCMEC/D3. DB enhanced the expressions of FAK signal transduction proteins and F-actin/globular actin (G-actin) ratio in rat brain and HCMEC/D3, suggesting that DB promotes actin cytoskeleton polymerization, benefits the endothelial cell–cell and cell–extracellular matrix adhesion, and, in consequence, contributes to BBB integrity.

ObjectivesTo explore the effects of weight change on the risk of metabolic abnormalities in the Chinese population.MethodsA total of 1895 metabolically healthy adults aged 21–78 years completed anthropometric and biological measurements at baseline (2012) and at an eight year follow-up (2020). Based on absolute weight change and relative weight change, the participants were split into five classes. A Cox proportional hazards regression model was used to estimate the relative risk (RR) and 95% confidence intervals (95% CI) for the risk of metabolic abnormalities using stable weight as the reference group. Stratified analysis was used to explore this relationship in participants with different baseline body mass index (BMI) levels.ResultsDuring the follow-up period, 35.41% of the participants retained a stable weight, and 10.71% had metabolic abnormalities. After covariate adjustment, for every kilogram gained over eight years, the risk of developing metabolic abnormalities increased by 22% (RR: 1.094; 95% CI: 1.063–1.127). Compared with stable weight participants, weight gain of 2–4 Kg and weight gain ≥ 4 Kg exhibited significantly higher risks of metabolic abnormalities, with RR of 1.700 (95% CI 1.150–2.513) and 1.981 (95% CI 1.372–2.859), respectively. A weight gain of ≥ 4 Kg had an opposite effect on the overweight/obesity and non-overweight/obesity groups, with an increased risk of metabolic abnormalities only in the non-overweight/obesity group (RR, 2.291; 95% CI, 1.331–3.942). Moreover, weight loss ≥ 4 Kg significantly reduced the risk of metabolic abnormalities only among overweight/obese adults (RR 0.373; 95% CI 0.154–0.906). Similar results were observed in relative body weight change analyses.ConclusionsLong-term excessive body weight gain is positively associated with an increased risk of metabolic abnormalities among adults with non-overweight/obesity, whereas long-term body weight loss is a protective factor for metabolic health among adults with overweight/obesity.

The risk of cardiovascular disease (CVD) is associated with unusual changes in the human gut microbiota, most commonly coronary atherosclerotic heart disease, hypertension, and heart failure. Immune mechanisms maintain a dynamic balance between the gut microbiota and the host immune system. When one side changes and the balance is disrupted, different degrees of damage are inflicted on the host and a diseased state gradually develops over time. This review summarizes the immune mechanism of the gut microbiota and its metabolites in the occurrence of common CVDs, discusses the relationship between gut-heart axis dysfunction and the progression of CVD, and lists the currently effective methods of regulating the gut microbiota for the treatment of CVDs.

Background: Exosomes, harboring donor-cell-derived biomarkers, are implicated in transferring oncologic protein and genetic materials. CD200, an immune checkpoint, has been engineered to affect immunosuppression in ovarian cancer. However, the potential of CD200 to serve as a predictor of ovarian cancers remains unexplored. Methods: We performed dynamic measurements of exosome-mediated or serum CD200 levels at primary diagnosis, post-operation, and three cycles after chemotherapy. The receiver operating characteristic curve and cumulative survival rate were paralleled to decode the predictive and prognostic profiles. Results: Independent enrichment and identification of exosomes revealed a significant concentration of CD200, predominantly located within these exosomes. The CD200 level was elevated in non-responders compared to responders at the serial points and significantly decreased after treatment. At the 335.50 pg/mL cut-off, CD200 at primary diagnosis enabled accurate discrimination between responders and non-responders with an area under the curve (AUC) of 0.94 (95% confidence interval (CI) = 0.902–0.979, p = 0.01). With the cut-off dropping from 311.00 pg/mL to 265.00 pg/mL, the AUC decreased from 0.918 (95% CI = 0.873–0.963, p = 0.02) to 0.908 (95% CI = 0.862–0.955, p = 0.02), respectively. Elevated levels of CD200 levels at both primary diagnosis and three cycles after chemotherapy were identified as independent predictors for poor progression-free survival (PFS) (hazard ratio (HR) = 2.8, 95% CI = 2.08–3.49, p = 0.01; HR = 6.7, 95% CI = 4.01–8.02, p = 0.01, respectively) and overall survival (OS) (HR = 3.5, 95% CI = 2.14–4.99, p = 0.04; HR = 5.6, 95% CI = 3.01–7.34, p = 0.01, respectively). Based on CD200 dynamics, patients were stratified into high- and low-AUC groups. High CD200-AUC was independently associated with unfavourable PFS and OS (HR = 4.6, 95% CI = 3.6–15.7, p = 0.01; HR = 3.2, 95% CI = 1.5–6.3, p = 0.01, respectively). Conclusions: This study proposes high exosome-mediated CD200 as a liquid-based biomarker indicative of chemotolerance and dismal survival in ovarian neoplasms.

Astrocytes, the most abundant cells in the brain, are integral to sleep regulation. In the context of a healthy neural environment, these glial cells exert a profound influence on the sleep-wake cycle, modulating both rapid eye movement (REM) and non-REM sleep phases. However, emerging literature underscores perturbations in astrocytic function as potential etiological factors in sleep disorders, either as protopathy or comorbidity. As known, sleep disorders significantly increase the risk of neurodegenerative, cardiovascular, metabolic, or psychiatric diseases. Meanwhile, sleep disorders are commonly screened as comorbidities in various neurodegenerative diseases, epilepsy, and others. Building on existing research that examines the role of astrocytes in sleep disorders, this review aims to elucidate the potential mechanisms by which astrocytes influence sleep regulation and contribute to sleep disorders in the varied settings of brain diseases. The review emphasizes the significance of astrocyte-mediated mechanisms in sleep disorders and their associated comorbidities, highlighting the need for further research.

ImportanceStable angina pectoris (SAP) often occurs in the elderly and is relatively stable for 1–3 months; however, if patients do not receive effective treatment, life-threatening acute myocardial infarction could occur. Patients with different clinical types of coronary heart disease have different intestinal flora. Baduanjin, a traditional Chinese Qigong, has been used as adjuvant therapy to improve the symptoms of patients with SAP.ObjectiveTo determine the effect of Baduanjin exercise on the symptoms of patients with SAP and the intestinal flora, explore the action links and targets of Baduanjin intervention in elderly patients with SAP, and explain its mechanism.DesignA single-center, single-blind, randomized controlled trial. Patients and outcome assessors were blinded to group allocation.SettingThe trial will be conducted at Guang'anmen Hospital of China Academy of Chinese Medical Sciences.ParticipantsOne hundred and eighty patients aged 60 to 80 years with stable angina pectoris (I–III) were intervened for 8 weeks and followed up for half a year.InterventionsAmong the screened patients, 180 patients will be randomly assigned to either the Baduanjin or the control group at a 1:1 ratio (exercise duration: for 3–5 times a week, for 8 weeks) of moderate-intensity Baduanjin or free activities.Main and secondary resultsThe main result is the total effective rate for angina pectoris symptoms; secondary results include the duration of angina pectoris, number of angina pectoris episodes per week, nitroglycerin consumption, nitroglycerin reduction rate, Seattle angina score (SAQ), quality of life (SF-36),Traditional Chinese Medicine (TCM) syndrome scores, electrocardiogram (ECG) changes, blood lipid serum hypersensitive C-reactive protein levels, intestinal flora changes, serum changes in the intestinal flora metabolite Trimetlylamine oxide (TMAO), and non-targeted liposome detection. Adverse events will be recorded throughout the experiment, and the data will be analyzed by researchers who did not know about the assignment.DiscussionThis study provides compelling evidence for at-home use of Baduanjin exercise to relieve SAP-associated symptoms.Trial registrationThis study was approved by the ethics committee of Guang'anmen Hospital of China Academy of Chinese Medical Sciences (2022-121-KY). The trial has been registered in Chinese Clinical Trial Registration Center (ChiCTR2200062450).

BackgroundBirthweight have profound impacts on health status throughout lifetime, however, the relationship between maternal ferritin level in pregnancy and birthweight of the newborn remains controversial.ObjectiveThis retrospective cohort research was to analyze the association between maternal ferritin levels during pregnancy with birthweight outcomes, primarily for low birthweight (LBW) and small for gestational age (SGA).MethodsNewborns weighing lower than 2,500 grams were defined as LBW. SGA is defined as birthweight lower than the 10th percentile of the distribution of newborns' birthweight of the same gestational age. Multivariable logistic regressions have been used to explore the association of maternal ferritin levels and birthweight related outcomes, in which the ferritin concentration was logarithm transformed in the model. We further used restricted cubic spline models to explore linear/non-linear dose–response manners of ferritin level and birthweight outcomes.ResultsA total of 3,566 pregnant women were included in the study. In the results of the present study, we observed that maternal ferritin levels were linearly associated with the risk of LBW (p-trend = 0.005) and SGA (p-trend = 0.04), with the adjusted odds ratios (ORs) of 1.78 (95% CI 1.37–2.32) for LBW and 1.87 (95% CI 1.38–2.54) for SGA with an increase in Ln-ferritin concentrations per unit. The adjusted ORs across quartiles of ferritin levels were 2.14 (95% CI 1.03–4.47) for Quartile 2, 3.13 (95% CI 1.47–6.69) for Quartile 3, and 3.63 (95% CI 1.52–8.68) for Quartile 4 for LBW. The adjusted ORs of LBW and SGA among women using supplemental iron were 0.56 (95% CI 0.38, 0.85) and 0.65 (95% CI 0.40, 1.05) compared with non-users, respectively.ConclusionsOur findings found a linear dose–response relationship between ferritin levels and an increased risk of poor birthweight outcomes, suggesting that maternal ferritin level during pregnancy may provide an additional predictor for differentiating poor birthweight related outcomes. Further exploration should be conducted to ensure maternal ferritin thresholds and iron supplement doses.

Vehicle exhaust (VE) is the primary cause of urban air pollution, which adversely affects the respiratory system, exacerbates lung diseases, and results in high mortality rates. However, the underlying mechanism of the pathogenesis is largely unclear. Here, we developed a Drosophila model to systematically investigate the effects of VE on their health and physiology. We found that VE significantly impaired life span and locomotion in Drosophila. Interestingly, there was an increase in bacterial load in the guts upon VE exposure, suggesting VE is able to induce dysbiosis in the guts. Microbiota depletion can ameliorate the impairment of life span and locomotion. VE causes permeability of intestinal epithelial cells and increases proliferation of intestinal cells, suggesting VE disrupts intestinal homeostasis. We elucidate the underlying mechanism by which VE triggers Imd and DUOX gene expression. Taken together, this Drosophila model provides insight into the pathogenesis of Drosophila exposure to VE, enabling us to better understand the specific role of microbiota.

IntroductionMeningitis caused by oral anaerobic bacteria is rare, especially when complicated with an infected intracranial aneurysm. This paper has described an extremely rare case of bacterial meningitis caused by a mixed infection of oral microflora dominated by anaerobes, which developed cerebral infarcts, brain abscess, intracranial aneurysm, and severe hydrocephalus during treatment.Case reportWe describe a 65-year-old male patient who was presented with fever and headache as the initial symptoms and then developed left ophthalmoplegia, right hemiplegia, and disturbance of consciousness. Brain imaging showed that intracranial lesions were increased progressively, and cerebral infarcts, brain abscesses, intracranial aneurysm, and severe hydrocephalus were appeared gradually. Eventually, we diagnosed it as anaerobic meningitis by making deoxyribonucleic acid sequencing from the brain abscess pus. After using an anti-microbial regimen that can sufficiently cover anaerobes, the patient's condition was effectively controlled.ConclusionAnaerobic meningitis can cause a series of intracranial complications. Among them, the intracranial aneurysm is extremely rare. When evidence shows that the infection originates from oral flora, physicians should consider the possibility of this type of encephalitis. An early diagnosis and timely treatment are crucial to improving the prognosis.

ObjectiveCoronavirus disease 2019 (COVID-19) and the accompanying isolation have changed resident life rhythms and behaviors. This study investigated the effects of the COVID-19 pandemic on metabolic syndrome (MetS) and its components in employees in southwestern China.MethodsThis retrospective cohort study included 3,777 employees of five institutions who underwent physical examinations at the Affiliated Hospital of Southwest Medical University for three consecutive years from 2018 to 2020. We collected data on participant age and sex and measured the component indices of metabolic syndrome, including waist circumference, blood pressure (systolic and diastolic), fasting blood glucose level, and blood lipid (triglyceride and high-density lipoprotein cholesterol) level. We applied t-, chi-square, Mann–Whitney U, and Friedman's M tests to compare metabolic variables at different times.ResultsThe incidence of MetS in 2020 was 18.6%, significantly higher than the prevalence of 15.7% before the epidemic. The number of abnormal MetS components following the COVID-19 lockdown was much greater than those in 2018 (P < 0.001) and 2019 (P < 0.001), with no significant variations between the two years (P = 0.142). All metabolic parameters, except for fasting blood glucose, were significantly worse than those pre-lockdown. The increase in the prevalence of MetS and all its abnormal components except for fasting glucose from 2019 to 2020 was significantly higher than that from 2018 to 2019. The change values between 2019–2020 and 2018–2019 for all indices except for diastolic blood pressure did not differ significantly between men and women. For all component indicators except for waist circumference, we observed no significant age differences in the growth differentials between the two periods (2019–2020 and 2018–2019).ConclusionsCOVD-19 lockdown have increased metabolic health risks among Chinese adults. Targeted measures, such as health education, are urgently needed to address poor metabolic health caused by the COVID-19 pandemic.

In the last two decades, there was a continuing declining participation rate in STEM education, especially in secondary schools in regional Australia. To reverse this trend and inspire rural school students with science and technology education, both federal and state governments identify the new strategies to promote STEM engagement of school students. In this study, with Queensland government's Engaging Science funding support, Central Queensland University researchers collaborated with rural school to deliver a demonstration with hand-on experiences of drone technologies to students. The activity led students to understand the application of drone technologies in daily life, especially agriculture sector. These activities impressed local communities including both teachers and students by demonstrating real-world problem-solving skills, with increasing over 25% participating students' interest in STEM education. This also leads more future collaboration opportunities to deliver other projects to supporting rural schools' STEM education. Future challenge for conducting these activities would be preparing the activity materials that fit the learning style and time schedule for different knowledge levels of students.

Atherosclerotic cardiovascular diseases (ASCVDs) are the most important diseases that endanger people’s health, leading to high morbidity and mortality worldwide. In addition, various thrombotic events secondary to cardiovascular and cerebrovascular diseases need must be considered seriously. Therefore, the development of novel anti-platelet drugs with high efficiency, and fewer adverse effects has become a research focus for preventing of cardiovascular diseases (CVDs). Blood-activation and stasis-removal from circulation have been widely considered as principles for treating syndromes related to CVDs. Blood-activating Chinese (BAC botanical drugs, as members of traditional Chinese medicine (TCM), have shown to improve hemodynamics and hemorheology, and inhibit thrombosis and atherosclerosis. Modern medical research has identified that a combination of BAC botanical drugs and anti-platelet drugs, such as aspirin or clopidogrel, not only enhances the anti-platelet effects, but also reduces the risk of bleeding and protects the vascular endothelium. The anti-platelet mechanism of Blood-activating Chinese (BAC) botanical drugs and their compounds is not clear; therefore, their potential targets need to be explored. With the continuous development of bioinformatics and “omics” technology, some unconventional applications of BAC botanical drugs have been discovered. In this review, we will focus on the related targets and signaling pathways of anti-atherosclerotic treatments involving a combination of BAC botanical drugs and anti-platelet drugs reported in recent years.

Nuclear receptor subfamily 0 group B member 1 gene (NR0B1) encodes an orphan nuclear receptor that plays a critical role in the development and regulation of the adrenal gland and hypothalamic–pituitary–gonadal axis. In this study, we report a novel mutation in NR0B1 that led to adult-onset adrenal hypoplasia congenita (AHC) and pubertal development failure in a male adult. Clinical examinations revealed hyponatremia, elevated adrenocorticotropic hormone levels, reduced testosterone and gonadotropin levels, and hyper-responses to gonadotropin-releasing hormone and human chorionic gonadotropin stimulation tests. Whole-exome sequencing and Sanger sequencing were performed to identify the potential causes of AHC. Candidate variants were shortlisted based on the X-linked recessive models. Sequence analyses identified a novel hemizygous variant of c.1034delC in exon 1 of NR0B1 at Xp21.2, resulting in a frameshift mutation and premature stop codon formation. The c.1034delC/p.Pro345Argfs*27 in the NR0B1 gene was detected in the hemizygous state in affected males and in the heterozygous state in healthy female family carriers. These results expand the clinical features of AHC as well as the mutation profile of the causative gene NR0B1. Further studies are needed to elucidate the biological effects of the mutation on the development and function of the adrenal gland and the hypothalamic–pituitary–gonadal axis.

BackgroundMedicinal dendrobiums are used popularly in traditional Chinese medicine for the treatment of diabetes, while their active compounds and mechanism remain unclear. This review aimed to evaluate the mechanism and active compounds of medicinal dendrobiums in diabetes management through a systematic approach.MethodsA systematic approach was conducted to search for the mechanism and active phytochemicals in Dendrobium responsible for anti-diabetic actions using databases PubMed, Embase, and SciFinder.ResultsCurrent literature indicates polysaccharides, bibenzyls, phenanthrene, and alkaloids are commonly isolated in Dendrobium genusin which polysaccharides and bibenzyls are most aboundant. Many animal studies have shown that polysaccharides from the species of Dendrobium provide with antidiabetic effects by lowering glucose level and reversing chronic inflammation of T2DM taken orally at 200 mg/kg. Dendrobium polysaccharides protect pancreatic β-cell dysfunction and insulin resistance in liver. Dendrobium polysaccharides up-regulate the abundance of short-chain fatty acid to stimulate GLP-1 secretion through gut microbiota. Bibenzyls also have great potency to inhibit the progression of the chronic inflammation in cellular studies.ConclusionPolysaccharides and bibenzyls are the major active compounds in medicinal dendrobiums for diabetic management through the mechanisms of lowering glucose level and reversing chronic inflammation of T2DM by modulating pancreatic β-cell dysfunction and insulin resistance in liver as a result from gut microbita regulation.

Background: The plasmid−mediated tigecycline resistance gene tet(X4) confers a high level of resistance to tigecycline. The experiment aims to investigate the prevalence and characterization of tet(X4) in Escherichia coli isolates from chicken and pig farms in Hunan province, China. Methods: A total of six tet(X4) positive strains were identified in 257 E. coli derived from chicken samples in Xiangtan city (n = 2), pig samples in Xiangxiang city (n = 1), Chenzhou city (n = 2), and Zhuzhou city (n = 1). The presence of tet(X4) was directly detected by PCR assay, and then the broth dilution method determined the antimicrobial susceptibility profile of the tet(X4)−positive isolates. Genomic locations were identified by whole−genome sequencing (WGS) and bioinformatics. Results: Almost all tet(X4)−positive strains showed high resistance to multidrug, including tigecycline. Resistome analysis revealed many antibiotic resistance genes, including those with resistance to tetracyclines, β−lactams, phenicols, quinolones, lincosamides chloramphenicol, aminoglycosides and sulfamids. These tet(X4)−bearing strains exhibited six distract STs, such as ST10, 202, ST218, ST362, ST2077, ST7068. The plasmid replicon types carrying tet(X4) were the hybrid plasmid IncFIA(HI1)/IncHIA/IncHIB(R27) (5/6) and IncX1 (1/6). Conclusions: The presence of similar genetic environments in E. coli from different cities suggests there may be horizontal transmission pathways promoting the broad spread of drug−resistant genes in Hunan Province, putting great pressure on multidrug resistance monitoring.

Objectives: To present the prenatal findings and the molecular cytogenetic analyses of a de novo interstitial deletion of 1q23.3 encompassing PBX1 gene. Case report: A 32-year-old woman (gravida 1, para 0) underwent amniocentesis at 26 weeks' gestation because of constant small fetal kidneys on prenatal ultrasound. Chromosome microarray analysis (CMA) detected a de novo deletion of 1.871 Mb at 1q23.3. The deletion encompassed 2 genes of PBX1 and LMX1A. PBX1 haploinsufficiency had been reported to lead syndromic congenital anomalies of kidney and urinary tract (CAKUT) in humans. Furthermore, at 31 weeks’ gestation, borderline oligohydramnios and restricted fetal dimensions were revealed. Ultimately, the pregnancy was terminated at 32 weeks with a 1500-g female fetus presenting polydactyl of left hand. Conclusions: The shared phenotypes between this case and the previously published prenatal cases demonstrate that loss of function mutation in PBX1 should be suspicious in fetus with bilateral renal hypoplasia, oligohydramnios and intrauterine growth retardation (IUGR). Keywords: PBX1, Renal hypoplasia, Prenatal diagnosis, Chromosome microarray analysis

Partial pressure of oxygen (pO2) in the kidney is maintained at a relatively stable level by a unique and complex functional interplay between renal blood flow, glomerular filtration rate (GFR), oxygen consumption, and arteriovenous oxygen shunting. The vulnerability of this interaction renders the kidney vulnerable to hypoxic injury, leading to different renal diseases. Hypoxia has long been recognized as an important factor in the pathogenesis of acute kidney injury (AKI), especially renal ischemia/reperfusion injury. Accumulating evidence suggests that hypoxia also plays an important role in the pathogenesis and progression of chronic kidney disease (CKD) and CKD-related complications, such as anemia, cardiovascular events, and sarcopenia. In addition, renal cancer is linked to the deregulation of hypoxia pathways. Renal cancer utilizes various molecular pathways to respond and adapt to changes in renal oxygenation. Particularly, hypoxia-inducible factor (HIF) (including HIF-1, 2, 3) has been shown to be activated in renal disease and plays a major role in the protective response to hypoxia. HIF-1 is a heterodimer that is composed of an oxygen-regulated HIF-1α subunit and a constitutively expressed HIF-1β subunit. In renal diseases, the critical characteristic of HIF-1α is protective, but it also has a negative effect, such as in sarcopenia. This review summarizes the mechanisms of HIF-1α regulation in renal disease.

Storage root formation of sweetpotato (Ipomoea batatas (L.) Lam) is a complex developmental process relating to the activity of cambium. Little information is available on the relationship between nitrogen (N) application levels and the initiation and development of sweetpotato storage roots (SRs). This study aims to examine how N application rates promoted/inhibited the formation and development of storage roots (SRs) for sweetpotato cultivar ‘Orleans’ during the first 8 weeks after planting. Cuttings were grown in coarse river sand culture supplied with modified Hoagland nutrient solution at four different rates (0 (N0), 50 (N50), 100 (N100) or 200 (N200) mg L−1) of N. The results showed that N100 treatment promoted the formation of primary and secondary cambium, resulting in a significant higher rate of SR formation between 21 and 56 days after transplanting (DAT). Due to the higher N demand after formation of SRs, N200 treatment displayed faster growth, higher N acquisition and the highest efficiency of N use after 35 DAT, but the SR formation rate and SR number per plant remained insignificantly lower than N100 when differentiation of adventitious root was mostly completed (49 DAT), suggesting irreversible an effect of N rate during SR initiation, which eventually affects SR number. The results suggested that the optimal substrate N level for sweetpotato SR initiation is lower than that for following SR growth, which should be considered in the fertilisation scheme.

Atherosclerosis (AS), especially atherosclerotic cardiovascular diseases (ASCVDs), and metabolic diseases (such as diabetes, obesity, dyslipidemia, and nonalcoholic fatty liver disease) are major public health issues worldwide that seriously threaten human health. Exploring effective natural product-based drugs is a promising strategy for the treatment of AS and metabolic diseases. Berberine (BBR), an important isoquinoline alkaloid found in various medicinal plants, has been shown to have multiple pharmacological effects and therapeutic applications. In view of its low bioavailability, increasing evidence indicates that the gut microbiota may serve as a target for the multifunctional effects of BBR. Under the pathological conditions of AS and metabolic diseases, BBR improves intestinal barrier function and reduces inflammation induced by gut microbiota-derived lipopolysaccharide (LPS). Moreover, BBR reverses or induces structural and compositional alterations in the gut microbiota and regulates gut microbe-dependent metabolites as well as related downstream pathways; this improves glucose and lipid metabolism and energy homeostasis. These findings at least partly explain the effect of BBR on AS and metabolic diseases. In this review, we elaborate on the research progress of BBR and its mechanisms of action in the treatment of AS and metabolic diseases from the perspective of gut microbiota, to reveal the potential contribution of gut microbiota to the multifunctional biological effects of BBR.

The high incidence of patients with chronic itch highlights the importance of fundamental research. Recent advances in the interface of gut microbiota have shed new light into exploring this phenomenon. However, it is unknown whether gut microbiota plays a role in chronic itch in rodents with or without cognitive dysfunction. In this study, the role of gut microbiota in diphenylcyclopropenone (DCP)-evoked chronic itch was investigated in mice and hierarchical cluster analysis of novel object recognition test (ORT) results were used to classify DCP-evoked itch model in mice with or without cognitive dysfunction (CD)-like phenotype and 16S ribosomal RNA (rRNA) gene sequencing was used to compare gut bacterial composition between CD (Susceptible) and Non-CD phenotypes (Unsusceptible) in chronic itch mice. Results showed that the microbiota composition was significantly altered by DCP-evoked chronic itch and chronic itch induced novel object recognition-related CD. However, abnormal gut microbiota composition induced by chronic itch may not be correlated with novel object recognition-related CD.

P-glycoprotein (P-gp) could maintain stability of the nerve system by effluxing toxins out of the blood-brain barrier. Whether it plays a very important role in drug brain distribution during space travel is not yet known. The present study was aimed at investigating P-gp function, expression, and its interacting proteins in a rat brain under simulated microgravity (SMG) by comparative proteomics approach. Rats were tail-suspended to induce short- (7-day) and long-term (21-day) microgravity. P-gp function was assessed by measuring the P-gp ATPase activity and the brain-to-plasma concentration ratio of rhodamine 123. P-gp expression was evaluated by Western blot. 21d-SMG significantly enhanced P-gp efflux activity and expression in rats. Label-free proteomics strategy identified 26 common differentially expressed proteins (DEPs) interacting with P-gp in 7d- and 21d-SMG groups. Most of the DEPs mainly regulated ATP hydrolysis coupled transmembrane transport and so on. Interaction analysis showed that P-gp might potentially interact with heat shock proteins, sodium/potassium ATP enzyme, ATP synthase, microtubule-associated proteins, and vesicle fusion ATPase. The present study firstly reported P-gp function, expression, and its potentially interacting proteins exposed to simulated microgravity. These findings might be helpful not only for further study on nerve system stability but also for the safe and effective use of P-gp substrate drugs during space travel.

Triple negative breast cancer (TNBC) accounts for less than a quarter of breast cancer but has the poorest survival outcome and is prone to relapse as well as metastasis due to its aggressiveness and lack of therapeutic target. Herein, we analyzed the TCGA datasets of lncRNA expressional profiles of breast cancer vs. normal tissue and TNBC vs. Non-TNBC subtypes and screened a long non-coding RNA (lncRNA) MNX1-AS1 overexpressing in TNBC. We found that MNX1-AS1 were upregulated in TNBC tumor tissues and correlated with poor survival outcome in TNBC patients. Silencing MNX1-AS1 reduced the aggressiveness of TNBC in vitro and in vivo. By using RNA pulldown assay followed by western blotting and RNA immunoprecipitation (RIP), we identified Stat3 was the MNX1-AS1 binding protein and MNX1-AS1 upregulated the phosphorylation of Stat3 by enhancing the interaction between p-JAK and Stat3. The present study suggested that targeting MNX1-AS1 may represent a promising therapeutic strategy to TNBC.

The present study aimed to investigate the change of intestinal mucosa proteins, especially the alteration of intestinal drug metabolizing enzymes (IDMEs) following 14-day simulated microgravity. Morey–Holton tail-suspension analog was used to simulate microgravity. Intestinal mucosa proteins of rats were determined by label-free quantitative proteomic strategy. A total of 335 differentially expressed proteins (DEPs) were identified, 190 DEPs were upregulated, and 145 DEPs were downregulated. According to bioinformatic analysis, most of DEPs exhibited hydrolase, oxidoreductase, transferase, ligase, or lyase catalytic activity. DEPs were mainly enriched in metabolic pathways, including metabolism of amino acid, glucose, and carbon. Moreover, 11 of DEPs were involved in exogenous drug and xenobiotics metabolism. Owing to the importance of IDMEs for the efficacy and safety of oral drugs, the expression of cytochrome P450 1A2 (CYP1A2), CYP2D1, CYP3A2, CYP2E1, alcohol dehydrogenase 1 (ADH1), and glutathione S-transferase mu 5 (GSTM5) in rat intestine mucosa was determined by Western-blot. The activity of ADH, aldehyde dehydrogenase (ALDH) and GST was evaluated. Compared with control rats, the expression of CYP1A2, CYP2D1, CYP3A2, and ADH1 in the simulated microgravity (SMG) group of rats were dramatically decreased by 33.16%, 21.93%, 48.49%, and 22.83%, respectively. GSTM5 was significantly upregulated by 53.14% and CYP2E1 expression did not show a dramatical change in SMG group rats. Moreover, 14-day SMG reduced ADH activity, while ALDH and GST activities was not altered remarkably. It could be concluded that SMG dramatically affected the expression and activity of some IDMEs, which might alter the efficacy or safety of their substrate drugs under microgravity. The present study provided some preliminary information on IDMEs under microgravity. It revealed the potential effect of SMG on intestinal metabolism, which may be helpful to understand the intestinal health of astronauts and medication use.

Background. IgG4-related hypophysitis (IgG4-RH) is a rare disease, and its prevalence remains unclear. In recent years, an increasing number of cases have been reported because of the increasing recognition of this disease. We aimed to summarize case reports of IgG4-RH and outline the clinical features and outcomes. Methods. We performed PubMed search of articles using the search terms “hypophysitis [AND] IgG4.” Consequently, only 54 English articles (76 cases) met Leporati’s diagnostic criteria. Results. Of the 76 cases, the ratio of men to women was 1.5 : 1, and the age at diagnosis was 54.1 ± 17.8 years. The median IgG4 concentration was 405.0 mg/dl. Anterior hypopituitarism, isolated central diabetes insipidus, and panhypopituitarism were observed in 14 (18.4%), 12 (15.8%), and 44 (57.9%) cases, respectively. The sequence of anterior hormone deficiency was as follows: gonadotropin (68.4%), ACTH (63.2%), TSH (59.2%), GH (48.7%), and prolactin (42.1%). The median number of involved organs was 1.5, and the lung (18.4%), retroperitoneum (17.1%), kidney (15.8%), submandibular glands (14.5%), and pancreas (13.2%) were the common involved organs. Elevated IgG4 concentration and normal IgG4 level were in 42 (76.4%) and 13 (23.6%) cases, respectively. Patients with elevated serum IgG4 concentration were older (60.9 ± 14.3 vs 45.6 ± 17.4, p=0.001) and male-prone (78.6% vs 40.4%, p=0.003) and had a susceptibility of multiple organ involvement (78.6% vs 35.0%, p=0.001) compared to those with normal serum IgG4 levels. Males were older at disease onset (61.5 ± 12.6 vs 42.9 ± 18.8, p

Loureirin B (LB) is the marker compound of dragon blood (DB), which exhibits great potentials in protecting astronauts’ health against radiation and simulated microgravity (SM). Pharmacokinetics of LB is reported to be significantly altered by SM. Here, we investigated key metabolic features of LB in rat liver microsome (RLM) and the effects of SM on LB metabolism as well as on expression of major hepatic cytochrome P450 (CYP450) isoforms. Ten metabolites were tentatively identified based on fragmentation pathways using LC-MS/MS method and elimination kinetics of LB followed a typical Michaelis–Menten equation (Vmax was 1.32 μg/min/mg and Km was 13.33 μg/mL). CYP1A2, CYP2C11, CYP2D1, and CYP3A2 were involved in the metabolism of LB and the relative strength was: CYP3A2 > CYP2C11 > CYP2D1 > CYP1A2. Comparative studies suggested that elimination of LB in RLM was remarkably increased by 3-day and 14-day SM, and the generation of identified metabolites was affected as well. Additionally, 3-day and 14-day SM showed obvious regulatory effects on the expression of major CYP450 isoforms, which might contribute to the increased elimination of LB. The data provided supports for the application of DB as a protective agent and the reasonable use of current medications metabolized by hepatic CYP450 in space missions.