Search

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of type 2 diabetes mellitus (T2DM). The pathogenesis of NAFLD involves multiple biological changes, including insulin resistance, oxidative stress, inflammation, as well as genetic and environmental factors. Liraglutide has been used to control blood sugar. But the impact of liraglutide on T2DM-associated NAFLD remains unclear. In this study, we investigated the impact and potential molecular mechanisms of inhibiting ferroptosis for liraglutide improves T2DM-associated NAFLD. Methods Mice were fed on high-fat-diet and injected with streptozotocin to mimic T2DM-associated NAFLD and gene expression in liver was analysed by RNA-seq. The fast blood glucose was measured during the period of liraglutide and ferrostatin-1 administration. Hematoxylin and eosin staining was used to evaluate the pathological changes in the liver. The occurrence of hepatic ferroptosis was measured by lipid peroxidation in vivo. The mechanism of liraglutide inhibition ferroptosis was investigated by in vitro cell culture. Results Liraglutide not only improved glucose metabolism, but also ameliorated tissue damage in the livers. Transcriptomic analysis indicated that liraglutide regulates lipid metabolism related signaling including AMPK and ACC. Furthermore, ferroptosis inhibitor rather than other cell death inhibitors rescued liver cell viability in the presence of high glucose. Mechanistically, liraglutide-induced activation of AMPK phosphorylated ACC, while AMPK inhibitor compound C blocked the liraglutide-mediated suppression of ferroptosis. Moreover, ferroptosis inhibitor restored liver function in T2DM mice in vivo. Conclusions These findings indicate that liraglutide ameliorates the T2DM-associated NAFLD, which possibly through the activation of AMPK/ACC pathway and inhibition of ferroptosis.

Abstract Background Dandelion has a great potential to be used as feed additive. Using microbial fermentation technology to degrade cell walls is conducive to enable better release of bioactive compounds of dandelion. This study intended to explore the effect of fermented dandelion (FD) on production performance, meat quality, immune function, and intestinal microbiota of broiler chickens. One-hundred and twenty 1-day-old male Arbor Acres broiler chickens were randomly allotted into three treatments: CON (basal diet, control), LFD and HFD (basal diet with 500 and 1000 mg/kg FD, respectively), with five replicates of eight birds each. The experiment lasted for 42 days. Results The results showed that birds in HFD group had increased ADG during 1–21 days (P

Abstract Background Periodontitis is a common chronic oral disease which seriously affects people's quality of life. Although human herpes simplex virus (HSV) is also found in periodontal lesions, the association between HSV infection and periodontitis is unclear. Methods The National Health and Nutrition Examination Survey (NHANES) data for 2009–2010, 2011–2012 and 2013–2014 was combined, and the association between HSV infection and periodontitis in the general population and particular subgroups was investigated through weighted multi-logistic analyses. Results There were 4,733 participants aged 30–50 years old with clinically assessed periodontitis concurrent with HSV infection. In general analysis, after adjusted for covariates, both HSV-1 (OR = 1.09, P

Abstract This paper is concerned with the adaptive tracking control problem for nonlinear systems with virtual control coefficients including known and unknown items. The known items are employed for controller design directly, such that more information is utilized to achieve better performance. To deal with the unknown items, a novel real control law is firstly constructed by introducing an auxiliary system. The proposed controller is designed and applied to an uncertain TCP/AQM network system, which guarantees the practical boundedness of all the signals in the closed-loop system. Finally, the effectiveness and practicability of the developed control strategy are validated by simulation results.

Abstract. In the field of plastic and reconstructive surgery, the loss of organs or tissues caused by diseases or injuries has resulted in challenges, such as donor shortage and immunosuppression. In recent years, with the development of regenerative medicine, the decellularization-recellularization strategy seems to be a promising and attractive method to resolve these difficulties. The decellularized extracellular matrix contains no cells and genetic materials, while retaining the complex ultrastructure, and it can be used as a scaffold for cell seeding and subsequent transplantation, thereby promoting the regeneration of diseased or damaged tissues and organs. This review provided an overview of decellularization-recellularization technique, and mainly concentrated on the application of decellularization-recellularization technique in the field of plastic and reconstructive surgery, including the remodeling of skin, nose, ears, face, and limbs. Finally, we proposed the challenges in and the direction of future development of decellularization-recellularization technique in plastic surgery.

To investigate the impact of electrode structure on Electrical Stimulation Therapy (EST) for chronic wound healing, this study designed three variants of flexible microelectrodes (FMs) with Ag-Cu coverings (ACCs), each exhibiting distinct geometrical configurations: hexagonal, cross-shaped, and serpentine. These were integrated with PPY/PDA/PANI (3/6) (full name: polypyrrole/polydopamine/polyaniline 3/6). Hydrogel dressing comprehensive animal studies, coupled with detailed electrical and mechanical modeling and simulations, were conducted to assess their performance. Results indicated that the serpentine-shaped FM outperformed its counterparts in terms of flexibility and safety, exhibiting minimal thermal effects and a reduced risk of burns. Notably, FMs with metal coverings under 3% demonstrated promising potential for optoelectronic self-powering capabilities. Additionally, simulation data highlighted the significant influence of hydrogel non-uniformity on the distribution of electrical properties across the skin surface, providing critical insights for optimizing EST protocols when employing hydrogel dressings.

Biofertilizers are environmentally friendly compounds that can enhance plant growth and substitute for chemically synthesized products. In this research, a new strain of the bacterium Bacillus velezensis, designated JZ, was isolated from the roots of strawberry plants and exhibited potent antagonistic properties against Bacillus altitudinis m-1, a pathogen responsible for leaf spot disease in strawberry. The fermentation broth of JZ exerted an inhibition rate of 47.43% against this pathogen. Using an optimized acid precipitation method, crude extracts of lipopeptides from the JZ fermentation broth were obtained. The crude extract of B. velezensis JZ fermentation broth did not significantly disrupt the cell permeability of B. altitudinis m-1, whereas it notably reduced the Ca2+-ATPase activity on the cell membrane and markedly elevated the intracellular reactive oxygen species (ROS) concentration. To identify the active compounds within the crude extract, QTOF-MS/MS was employed, revealing four antimicrobial compounds: fengycin, iturin, surfactin, and a polyene antibiotic known as bacillaene. The strain JZ also produced various plant-growth-promoting substances, such as protease, IAA, and siderophore, which assists plants to survive under pathogen infection. These findings suggest that the JZ strain holds significant potential as a biological control agent against B. altitudinis, providing a promising avenue for the management of plant bacterial disease.

As a result of continuing scientific and technological progress, electromagnetic waves have become increasingly pervasive across a variety of domains, particularly within the microwave frequency range. These waves have found extensive applications in wireless communications, high-frequency electronic circuits, and several related fields. As a result, absorptive materials have become indispensable for dual-use applications across both the military and civilian domains because of their exceptional electromagnetic wave absorption properties. This paper, beginning with the operating mechanisms of absorptive materials, aims to provide an overview of the strategies that have been used to enhance the absorption performance of iron-based magnetic absorbers (IBMAs) and discuss the current research status of absorptive material components. The fabrication of a ferromagnetic absorber in terms of morphology, heterointerface coupling, and macrostructural enhancements and the effect of powder characteristics on their electromagnetic properties are discussed. Additionally, the application of IBMAs in elastomers is summarized. Finally, this paper summarizes the limitations of existing ferromagnetic absorber materials and offers a perspective on their potential future developments. The objective of the ongoing research is to fabricate absorptive components that have thin profiles, lightweight construction, wide absorption frequency ranges, and strong absorption capabilities.

Research on Chinese parenting styles using representative samples is limited, particularly during COVID-19, with most studies focusing on individual factors while neglecting regional influences. This study examines the impact of provincial income inequality, measured by the Gini coefficient, on parenting styles and how these effects vary across subgroups. Using data from the China Family Panel Studies (CFPS) 2020, encompassing 3768 children aged 7–16 years from 25 regions, we employed a multinomial logistic regression model to analyze the predictability of provincial income inequality on parenting styles identified through latent class analysis. Three parenting styles emerged during the first year of COVID-19: authoritarian (48.2%), autonomy granting (27.7%), and average-level undifferentiated (24.1%). A higher Gini coefficient related to a greater likelihood of parents adopting authoritarian or autonomy-granting parenting styles over average-level undifferentiated parenting. Subgroup analyses revealed a higher likelihood of adopting autonomy-granting and authoritarian parenting for male children compared to female. Mothers with lower education levels and parents in rural areas tend to favor authoritarian parenting in response to higher income inequality. This trend was less evident among more educated mothers and parents living in urban areas. These findings suggest that parenting styles in China are influenced by complex and region-specific factors.

Coronary artery disease (CAD) is a common comorbidity of type 2 diabetes mellitus (T2DM). However, the pathophysiology connecting these two phenotypes remains to be further understood. Combined analysis in multi-ethnic populations can help contribute to deepening our understanding of biological mechanisms caused by shared genetic loci. We applied genetic correlation analysis and then performed conditional and joint association analyses in Chinese, Japanese, and European populations to identify the genetic variants jointly associated with CAD and T2DM. Next, the associations between genes and the two traits were also explored. Finally, fine-mapping and functional enrichment analysis were employed to identify the potential causal variants and pathways. Genetic correlation results indicated significant genetic overlap between CAD and T2DM in the three populations. Over 10,000 shared signals were identified, and 587 were shared by East Asian and European populations. Fifty-six novel shared genes were found to have significant effects on both CAD and T2DM. Most loci were fine-mapped to plausible causal variant sets. Several similarities and differences of the involved genes in GO terms and KEGG pathways were revealed across East Asian and European populations. These findings highlight the importance of immunoregulation, neuroregulation, heart development, and the regulation of glucose metabolism in shared etiological mechanisms between CAD and T2DM.

An analysis method of normalized pressure–impulse (P-I) diagrams related to the ductility ratio of structural components is proposed, to quickly estimate the dynamic response of high-strength reinforcement concrete (RC) beams subjected to long-duration blast loading. Firstly, the overall bending deformation mode of RC beams is uncovered via explosion tests in a closed chamber, where the durations of the near-planar blast loadings are varied within 80–105 ms. Then, a single-degree-of-freedom (SDOF) model is established based on the bending deformation mode. The resistance function for the uniform pressure loading is developed using a novel approach, consisting of (1) developing and benchmarking a three-dimensional (3D) improved steel–concrete separated finite-element (FE) model; (2) using the benchmarked FE model to conduct numerical simulations for uniform pressure loading; and (3) idealizing the resistance function for uniform pressure using a bilinear relationship. Finally, the SDOF model is used to conduct parametric analyses and develop a normalized P-I diagram that can be used to analyze or design RC beams for far-field blast effects. This P-I diagram is verified using results from blast load tests that are primarily in the dynamic region. A total of 188 additional 3D nonlinear FE analyses of RC beams are conducted to expand the database in the impulse and quasi-static regions. Considering the limitations of the proposed method in predicting the shear-dominated deformation and the fracture behavior of members, the P-I diagram is applicable to the dynamic response of the bending deformation of members under far-field explosion, which can provide an important reference for the blast-resistant design and analysis of high-strength RC beams.

Abstract Currently, in multitrain DC subway system, abnormal increase of rail potential (RP) and stray current (SC) has seriously threatened the safe operation of the system. Over voltage protection device (OVPD) is generally chosen to control the RP, but its action process may increase the amplitude of SC seriously. Here, the grounding resistance of OVPD is optimized by a proposed multi‐objective decomposition algorithm based on differential evolution (MOEA/D‐DE) to suppress the rise of RP and SC synergistically. Firstly, the simulation model of the DC subway system with multitrain is built, the power flow calculation is conducted, and the dynamic RP and leakage current (LC) at the location of traction substation are obtained. Secondly, the double objective optimization model of maximum RP and LC is established and solved by MOEA/D‐DE. Finally, the effectiveness of the proposed method is verified based on the data of Guangzhou Metro Line 2. Results show that the SC of the system can be controlled effectively with OVPD grounding mode after optimization, and integrated control of RP and SC can be accomplished.

Abstract Transcriptional programs are often dysregulated in cancers. A comprehensive investigation of potential regulons is critical to the understanding of tumorigeneses. We first constructed the regulatory networks from single-cell RNA sequencing data in human lung adenocarcinoma (LUAD). We next introduce LPRI (Lung Cancer Prognostic Regulon Index), a precision oncology framework to identify new biomarkers associated with prognosis by leveraging the single cell regulon atlas and bulk RNA sequencing or microarray datasets. We confirmed that LPRI could be a robust biomarker to guide prognosis stratification across lung adenocarcinoma cohorts. Finally, a multi-omics data analysis to characterize molecular alterations associated with LPRI was performed from The Cancer Genome Atlas (TCGA) dataset. Our study provides a comprehensive chart of regulons in LUAD. Additionally, LPRI will be used to help prognostic prediction and developing personalized treatment for future studies.

Invasive fungal infections (IFIs) have been associated with high mortality, highlighting the urgent need for developing novel antifungal strategies. Herein the first light-responsive antifungal agents were designed by optical control of fungal ergosterol biosynthesis pathway with photocaged triazole lanosterol 14α-demethylase (CYP51) inhibitors. The photocaged triazoles completely shielded the CYP51 inhibition. The content of ergosterol in fungi before photoactivation and after photoactivation was 4.4% and 83.7%, respectively. Importantly, the shielded antifungal activity (MIC80 ≥ 64 μg/mL) could be efficiently recovered (MIC80 = 0.5–8 μg/mL) by light irradiation. The new chemical tools enable optical control of fungal growth arrest, morphological conversion and biofilm formation. The ability for high-precision antifungal treatment was validated by in vivo models. The light-activated compound A1 was comparable to fluconazole in prolonging survival in Galleria mellonella larvae with a median survival of 14 days and reducing fungal burden in the mouse skin infection model. Overall, this study paves the way for precise regulation of antifungal therapy with improved efficacy and safety.

Abstract The FK506-binding protein 51 (FKBP51, encoded by FKBP5 gene) has emerged as a critical regulator of mammalian endocrine stress responses and as a potential pharmacological target for metabolic disorders, including type 2 diabetes (T2D). However, in β cells, which secrete the only glucose-lowering hormone—insulin, the expression and function of FKBP5 has not been documented. Here, using human pancreatic tissue and primary human islets, we demonstrated the abundant expression of FKBP5 in β cells, which displayed an responsive induction upon acute inflammatory stress mimicked by in vitro treatment with a cocktail of inflammatory cytokines (IL-1β, IFN-γ, and TNF-α). To explore its function, siRNAs targeting FKBP5 and pharmacological inhibitor SAFit2 were applied both in clonal NIT-1 cells and primary human/mice islets. We found that FKBP5 inhibition promoted β-cell survival, improved insulin secretion, and upregulated β-cell functional gene expressions (MAFA and NKX6.1) in acute-inflammation stressed β cells. In primary human and mice islets, which constitutively suffer from inflammation stress during isolation and culture, FKBP5 inhibition also presented decent performance in improving islet function, in accordance with its protective effect against inflammation. Molecular studies found that FKBP5 is an important regulator for FOXO1 phosphorylation at Serine 256, and silencing of FOXO1 abrogated the protective effect of FKBP5 inhibition, suggesting that it is the key downstream effector of FKBP5 in β cells. At last, in situ detection of FKBP5 protein expression on human and mice pancreases revealed a reduction of FKBP5 expression in β cells in human T2D patients, as well as T2D mice model (db/db), which may indicate a FKBP5-inhibition-mediated pro-survival mechanism against the complex stresses in T2D milieus.

Abstract Due to the limited capacity of the adult mammalian brain to self-repair and regenerate, neurological diseases, especially neurodegenerative disorders and stroke, characterized by irreversible cellular damage are often considered as refractory diseases. Neural stem cells (NSCs) play a unique role in the treatment of neurological diseases for their abilities to self-renew and form different neural lineage cells, such as neurons and glial cells. With the increasing understanding of neurodevelopment and advances in stem cell technology, NSCs can be obtained from different sources and directed to differentiate into a specific neural lineage cell phenotype purposefully, making it possible to replace specific cells lost in some neurological diseases, which provides new approaches to treat neurodegenerative diseases as well as stroke. In this review, we outline the advances in generating several neuronal lineage subtypes from different sources of NSCs. We further summarize the therapeutic effects and possible therapeutic mechanisms of these fated specific NSCs in neurological disease models, with special emphasis on Parkinson’s disease and ischemic stroke. Finally, from the perspective of clinical translation, we compare the strengths and weaknesses of different sources of NSCs and different methods of directed differentiation, and propose future research directions for directed differentiation of NSCs in regenerative medicine.

Wheat embryo globulin (WEG) has been proven to possess multiple biological activities, including antioxidative properties, immunomodulatory, and so on. Aged mouse model were established by subcutaneous injection of D-galactose (D-gal), and the effects of WEG on learning, memory, and antioxidant capacity in aging mice were explored through behavioural tests and antioxidant enzyme activities determination. Compared with the Model group, WEG improved the percentage of the platform quadrant, increased the number of crossing platforms, and enhanced the identification indexs. WEG also increased total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities in the liver and brains of aging mice, and reduced malondialdehyde (MDA) content. Pathological observations indicated that WEG protected against damage to brain in D-gal-induced aging mice. These results effectively revealed that WEG not only improved the abilities of learning and memory, and the cognitive impairment, but also delayed the aging process of the D-gal-induced mice.

The physicochemical properties and composition of coix seed oil produced by Monascus purpureus fermentation and supercritical CO2 extraction were determined. Anti-lipid-oxidation and edible safety were evaluated using a cholesterol-fish oil model, acute oral toxicity assay, and genetic toxicity assay in vitro and in vivo, respectively. The results show that the extraction oil from fermented coix seed (FCS-O) had good physicochemical quality and abundant active components with physiological function. In particular, γ-tocotrienol, γ-oryzanol, coixenolide and oleic acid concentrations reached 72.83 µg/g, 745.96 µg/g, 9.65mg/g and 316.58 mg/100 g DW, respectively. The FCS-O exhibited higher antioxidant capability in inhibiting lipid oxidation and peroxidation. Compared to the blank control, the concentrations of 7-ketocholestreol and peroxide only were 8.42 µg/mL and 16.16 mmol/kg at 168 h of oxidation (P < 0.01). In addition, the FCS-O has been confirmed to be a very safe edible oil, with no acute toxicity (LD50 > 10 g/kg bw, considered actually non-toxic) and no induced mutagenicity, cytotoxicity or genotoxicity. These results serve as a good safety reference for future application of the oil from fermented coix seed. The development and utilization of this kind of oil will be beneficial as a food, food ingredient, nutritional supplement, or natural food antioxidant to promote good health function.

Abstract Background Coagulation function monitoring is important for the occurrence and development of diabetes. A total of 16 related proteins are involved in coagulation, but how these proteins change in diabetic urine exosomes is unclear. To explore the expression changes of coagulation-related proteins in urine exosomes and their possible roles in the pathogenesis of diabetes, we performed proteomic analysis and finally applied them to the noninvasive monitoring of diabetes. Methods Subject urine samples were collected. LC-MS/MS was used to collect the information on coagulation-related proteins in urine exosomes. ELISA, mass spectrometry and western blotting were used to further verify the differential protein expression in urine exosomes. Correlations with clinical indicators were explored, and receiver operating characteristic (ROC) curves were drawn to evaluate the value of differential proteins in diabetes monitoring. Results Analyzing urine exosome proteomics data, eight coagulation-related proteins were found in this study. Among them, F2 was elevated in urine exosomes of diabetic patients compared with healthy controls. The results of ELISA, mass spectrometry and western blotting further verified the changes in F2. Correlation analysis showed that the expression of urine exosome F2 was correlated with clinical lipid metabolism indexes, and the concentration of F2 was strongly positively correlated with blood TG levels (P

Abstract The ubiquitin-proteasome system (UPS) controls protein turnover, and its dysfunction contributes to human diseases including cancer. Deubiquitinating enzymes (DUBs) remove ubiquitin from proteins to maintain their stability. Inhibition of DUBs could induce the degradation of selected oncoproteins and has therefore become a potential therapeutic strategy for cancer. The deubiquitylase OTUD3 was reported to promote lung tumorigenesis by stabilizing oncoprotein GRP78, implying that inhibition of OTUD3 may be a therapeutic strategy for lung cancer. Here, we report a small-molecule inhibitor of OTUD3 (named OTUDin3) by computer-aided virtual screening and biological experimental verification. OTUDin3 exhibited pronounced antiproliferative and proapoptotic effects by inhibiting deubiquitinating activity of OTUD3 in non-small-cell lung cancer (NSCLC) cell lines. Moreover, OTUDin3 efficaciously inhibited growth of lung cancer xenografts in mice. In summary, our results support OTUDin3 as a potent inhibitor of OTUD3, the inhibition of which may be a promising therapeutic strategy for NSCLC.

Abstract Itch is a complex aversive sensory and emotional experience. As a most upsetting symptom in many dermatological and systemic diseases, it lacks efficient treatments. The lateral habenula nucleus (LHb) encodes negative emotions in the epithalamus and has been implicated in pain and analgesia. Nevertheless, the role of the lateral habenula nucleus in the pruritic sensation and emotion remains elusive. Here we defined the crucial role of glutamatergic neurons within the lateral habenula nucleus (GluLHb) in itch modulation in mice. We established histamine-dependent and histamine-independent models of acute pruritus, as well as the acetone-ether-water (AEW) model of chronic pruritus. We first assessed the effects of pruritogen injection on neural activation in both medial and lateral divisions of LHb in vitro. We then demonstrated that the population activity of GluLHb neurons was increased during the acute itch and chronic itch-induced scratching behaviors in vivo. In addition, electrophysiological data showed that the excitability of GluLHb neurons was enhanced by chronic itch. Chemogenetic suppression of GluLHb neurons disrupted both acute and chronic itch-evoked scratching behaviors. Furthermore, itch-induced conditioned place aversion (CPA) was abolished by GluLHb neuronal inhibition. Finally, we dissected the LHb upstream brain regions. Together, these findings reveal the involvement of LHb in processing both the sensational and emotional components of pruritus and may shed new insights into itch therapy.

Abstract To achieve optimal thermoelectric performance, it is crucial to manipulate the scattering processes within materials to decouple the transport of phonons and electrons. In half-Heusler (hH) compounds, selective defect reduction can significantly improve performance due to the weak electron-acoustic phonon interaction. This study utilized Sb-pressure controlled annealing process to modulate the microstructure and point defects of Nb0.55Ta0.40Ti0.05FeSb compound, resulting in a 100% increase in carrier mobility and a maximum power factor of 78 µW cm−1 K−2, approaching the theoretical prediction for NbFeSb single crystal. This approach yielded the highest average zT of ~0.86 among hH in the temperature range of 300-873 K. The use of this material led to a 210% enhancement in cooling power density compared to Bi2Te3-based devices and a conversion efficiency of 12%. These results demonstrate a promising strategy for optimizing hH materials for near-room-temperature thermoelectric applications.

Abstract Background Planktonic bacteria and archaea play a key role in river nutrient biogeochemical cycling; however, their respective community assembly and how to maintain their diversity are not well known in dammed rivers. Therefore, a seasonal survey of planktonic bacterial and archaeal community compositions and related environmental factors was conducted in 16 cascade reservoirs and corresponding river waters on the Wujiang River and the Pearl River in southwest China to understand the above mechanisms. Results Deterministic processes dominated bacterial and archaeal community assembly. The structural equation models showed that water temperature can directly or indirectly affect the microbial diversity. Interestingly, planktonic bacterial diversity increased with increasing water temperature, while archaea showed the opposite trend; the overall diversity of bacteria and archaea was no significant changes with changeable water temperature. Abundant microbes had a stronger distance–decay relationship than middle and rare ones, and the relationship was stronger in winter and spring than in summer and autumn. Conclusions Planktonic bacteria and archaea in dammed rivers had different biogeographic distributions, and water temperature was a key controlling factor. The different responses of planktonic bacterial and archaeal diversity to water temperature could be due to their different phylogenetic diversity. This ultimately maintained the stability of total microbial community diversity. This study reveals the different responses of planktonic bacteria and archaea to water temperature and perfects the theoretical framework for planktonic microbial biogeography in dammed rivers.

The COVID-19 pandemic continues to impact daily life worldwide. It would be helpful and valuable if we could obtain valid information from the COVID-19 pandemic sequential data itself for characterizing the pandemic. Here, we aim to demonstrate that it is feasible to analyze the patterns of the pandemic using a time-series clustering approach. In this work, we use dynamic time warping distance and hierarchical clustering to cluster time series of daily new cases and deaths from different countries into four patterns. It is found that geographic factors have a large but not decisive influence on the pattern of pandemic development. Moreover, the age structure of the population may also influence the formation of cluster patterns. Our proven valid method may provide a different but very useful perspective for other scholars and researchers.

Abstract Objective Our study was conducted aimed at investigating the potential correlation between cerebral microangiopathy and autonomic nervous dysfunction. Methods We initially included 164 hospitalized patients with cerebral microangiopathy at our hospital from November 2019 to January 2021. Based on the inclusion and exclusion criteria, a final total of 162 patients with cerebral microangiopathy were selected. According to the patient's Autonomic Symptom Profile (ASP) score, patients with a score greater than 22 were categorized into a group with concomitant autonomic dysfunction (71 cases, combined group), while those with a score below 22 were categorized into a group of isolated cerebral microangiopathy (83 cases, cerebral microangiopathy group). The general data and laboratory examination results of the two groups were analyzed, and Pearson correlation analysis was performed to evaluate the correlation between cerebral microangiopathy and autonomic dysfunction, as well as the influencing factors of cerebral microangiopathy patients combined with autonomic dysfunction. Results There were no significant differences between the two groups in terms of sex, BMI, smoking, drinking, family dementia history, diabetes, hypothyroidism, carotid atherosclerosis, obstructive sleep apnea hypopnea syndrome, hyperuricemia, hyperlipidemia, chronic obstructive pulmonary disease, Hamilton Anxiety Scale score, Hamilton Depression Scale score, 24‐h mean systolic blood pressure (SBP), 24‐h mean diastolic blood pressure DBP, daytime mean systolic blood pressure (dSBP), daytime mean diastolic blood pressure, nighttime mean systolic blood pressure (nSBP), nighttime mean diastolic blood pressure, 24‐h systolic blood pressure standard deviation (SBPSD), 24‐h diastolic blood pressure standard deviation, daytime diastolic blood pressure standard deviation, nighttime diastolic blood pressure standard deviation (nDBPSD), nDBPSD (p > .05). However, significant differences were observed between the two groups regarding age, history of coronary heart disease, hypertension, leukoaraiosis, cognitive function, ASP score, SSR, 24‐h SBPSD, daytime systolic blood pressure standard deviation (dSBPSD), nighttime systolic blood pressure standard deviation (nSBPSD), standard deviation of RR interval (SDNN), root mean square value of successive RR interval difference (RMSSD), high‐frequency component (HF), and low‐frequency component (LF) (p .05), but there were significant differences in blood uric acid and homocysteine (Hcy) levels (p

Online learning has evolved as an attractive and viable option for education, yet there is a need for further research to investigate the factors contributing to students' online learning anxiety regarding the college English course. Based on Keegan's distance education framework, this study examines the factors impacting online learning anxiety among English as foreign language (EFL) students in the Chinese context during the post-COVID-19 era. Data were collected from 899 EFL students across different regions of China through an online survey. Follow-up interviews with ten students provided additional insights into the association between online English learning and anxiety. The collected data underwent descriptive analysis, exploratory factor analysis, reliability analysis, and multiple linear regression analysis to examine the relationship between online learning anxiety and the identified factors. The results of our study indicate that many Chinese EFL students experienced different degrees of anxiety, ranging from mild to moderate or severe. Moreover, online learning anxiety among Chinese EFL students was positively predicted by a lack of learning motivation, separation from instructors, separation from peers, and technological challenges, while a lack of two-way communication negatively predicted it. The findings underscore the importance of taking effective measures and offering psychological guidance for Chinese EFL students to alleviate anxiety and facilitate their successful adaptation to the new normal of online learning.

ObjectivesTo evaluate the effects of platinum-based neoadjuvant chemotherapy (NACT) on the STING/IFN pathway and tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC), as well as clinicopathological factors affecting patient survival.Materials and methodsA total of 68 patients aged 34-77 years with NSCLC who received neoadjuvant chemotherapy and surgical treatment from March 2012 to February 2019 were reviewed, and the clinical pathological data and paired tissue specimens before and after NACT were collected. Immunohistochemistry and immunofluorescence were used to detect the protein levels of STING, PD-L1 and IFN-β, and the infiltration density of CD3+ TILs and CD8+TILs. The correlation between the expression of STING, PD-L1, IFN-β and the infiltration density of CD3+ TILs and CD8+ TILs as well as the clinicopathological characteristics before and after NACT was analyzed. The relationship between the related indexes, clinicopathological features and prognosis was also discussed.ResultsNACT increased the expression of STING, IFN-β and PD-L1 in tumor cells, and the infiltration of CD3+ and CD8+ TILs. In addition, ypTNM stage, ypN stage, changes in CD3+ TILs and in PD-L1 were associated with DFS (disease-free survival). CD3+ TILs changes and ypN stage were associated with OS (overall survival). Notably, ypN stage and CD3+ TILs changes were independent prognostic factors for DFS and OS.ConclusionNACT stimulates STING/IFN-β pathway, promotes infiltration of CD3+ and CD8+ TILs, triggers innate and adaptive immunity, and also upregulates PD-L1, which complemented the rationale for neoadjuvant chemotherapy in combination with immunotherapy. In addition, DFS was longer in patients with ypTNM I, ypN0-1, and elevated CD3+TILs after NACT. Patients with ypN0 and elevated CD3+ TILs after NACT had better OS benefits.

The demand for high‐performance materials in thermoelectric (TE) technology has driven continuous efforts to enhance the performance of commercialized Bi2Te3‐based thermoelectric materials. Here, we report success in achieving significant performance improvements in n‐type Bi2Te2.8Se0.2S0.01 through the implementation of a hot extrusion manufacturing process. This tailored manufacturing process has yielded a desired microstructure characterized by grain growth and preferred orientations. The resulting enlarged grain‐based microstructure exhibits reduced dislocations and defects that originated from plastic deformation during extrusion and post annealing. As such, the charge carrier mobility is significantly enhanced, leading to an ultrahigh power factor of approximately 51 μW cm−1 K−2 at ambient temperature. Consequently, a maximum figure of merit (zT) of 1.12 is achieved at 348 K in the combination of extrusion and annealing procedures. Using the synthesized n‐type Bi2Te2.8Se0.2S0.01 material, full‐scale cooling modules have been fabricated. These modules demonstrate record cooling performance, with a maximum temperature difference (ΔT) of 73.9 K at a hot‐side temperature of 300 K and a maximum cooling power density of 2.2 W cm−2. The cooling performance of these TE devices surpasses that of commercially available devices, establishing their potential for next‐generation TE cooling applications.

Anti-metabotropic glutamate receptor 1 encephalitis is an uncommon autoimmune condition characterized by a subacute onset of cerebellar syndrome. Frequently, it also manifests as sleep disorders and cognitive or behavioral changes. While immunotherapy is the primary treatment approach, the disease remains poorly understood. Herein, we present a case of anti-metabotropic glutamate receptor 1 encephalitis, highlighting its primary cerebellar syndrome manifestation. The first magnetic resonance imaging scan showed no obvious abnormality. Lumbar puncture showed increased cerebrospinal fluid pressure, increased white blood cell count and protein level. The next-generation sequencing of cerebrospinal fluid showed Epstein–Barr virus infection, and the patient was diagnosed with viral cerebellar encephalitis. However, antiviral therapy was ineffective. Finally, anti-metabotropic glutamate receptor 1 was measured at 1:1,000, and the patient was definitely diagnosed with anti-metabotropic glutamate receptor 1 encephalitis. Therefore, clinicians should pay attention to such diseases to avoid misdiagnosis.

Ferroptosis and cuproptosis, regulated forms of cell death resulting from metal ion accumulation, are closely related in terms of occurrence, cell metabolism, signaling pathways, and drug resistance. Notably, it is now understood that these processes play crucial roles in regulating physiological and pathological processes, especially in tumor development. Consequently, ferroptosis and cuproptosis have gained increasing significance as potential targets for anti-cancer drug development. This article systematically outlines the molecular mechanisms and cross-talk components of both ferroptosis and cuproptosis, elucidating their impacts on cancer. Furthermore, it investigates the clinical perspective of targeted ferroptosis and cuproptosis in cancer chemotherapy, immunotherapy, and radiotherapy. Our discussion extends to a comparative analysis of nanoparticles developed based on the mechanisms of ferroptosis and cuproptosis in cancer, contrasting them with current conventional therapies. Opportunities and challenges in cancer treatment are explored, emphasizing the potential therapeutic direction of co-targeting ferroptosis and cuproptosis. The article also attempts to analyze the clinical applications of this co-targeting approach for cancer treatment while summarizing the existing barriers that require overcoming.

BackgroundFree throws serve as a crucial scoring mechanism in basketball games. As the level of basketball and the intensity of competition continue to improve, the frequency of free throw attempts gradually rises. However, with heightened game intensity, maintaining a consistent free throw success rate becomes increasingly challenging. The aim of this study was to investigate the eye movement characteristics exhibited by basketball players during free throws of varying intensities, as well as explore the relationship between these eye movement characteristics and free throw percentage.MethodsTwenty elite female basketball players were recruited to perform free throws at varying exercise intensities (low, moderate, and high) while wearing an eye tracker device. Eye tracking data was collected using the Tobii Glasses 3 eye tracker. Additionally, the Polar team pro, a heart rate monitoring system manufactured in Finland, was utilized to monitor participants' heart rates during different exercise intensities.ResultsThe average number of fixations on the hoop and net during free throws of varying intensities exhibited statistically significant differences (P < 0.05). The fixation durations of the hoop, backboard, and net exhibited statistically significant differences (P < 0.05). Notably, the hoop accounted for the highest proportion of the overall average fixation duration. high-intensity free throws necessitate lengthier processing durations compared to low-intensity and medium-intensity free throws. Furthermore, for free throws of moderate intensity, there was a significant negative correlation between the number of fixations on the hoop and free throw percentage (P < 0.05). Conversely, for high intensity free throws, there was a significant positive correlation between the fixation duration on the hoop and free throw percentage (P < 0.05).ConclusionsUnder the three kinds of sports intensity, the players mainly focus on the hoop position, the moderate intensity free throw has the best stability, and the information search strategy and information processing efficiency are the highest. In high intensity free throws, the longer the fixation duration at the hoop, the higher the free throw percentage; The higher the number of fixations at the hoop, the lower the percentage of free throws.

BackgroundFree throw is an important means of scoring in basketball games. With the improvement of basketball competition level and the enhancement of confrontation degree, the number of free throws in the game gradually increases, so the score of free throw will have an important impact on the result of the game. The purpose of this study is to explore the relationship between visual attention characteristics and hit rate of basketball players in free throw psychological procedure training, so as to provide scientific basis for basketball teaching and training.MethodsForty players with similar free throw abilities were randomly assigned to the experimental group (10 males, 10 females) and control group (10 males, 10 females). The experimental group was free throw psychological procedure training, while the control group was trained with routine training, Eye movement indices (number of fixations, fixation duration, and pupil dilation) and the free throw hit rate and analyzed before and after the experiment. Group differences were examined using t-tests, while paired sample t-tests were conducted to compare pre- and post-test results within each group. The training time and training times of the two groups were the same.ResultsThere were significant differences in fixation duration, number of fixations, pupil diameter and free throw hit rate between pre-test and post-test in the experimental group (P < 0.05). Post-test, there were significant differences in number of fixations, fixation duration, pupil diameter and free throw hit rate between the two groups (P < 0.05). There was a significant positive correlation between number of fixations and free throw hit rate in top (P < 0.01), and there was a significant positive correlation between fixation duration and hit rate in front (P < 0.01).ConclusionsThe psychological procedure training can improve the visual information search strategy and information processing ability of free throw, and significantly improve the free throw hit rate. There was a positive correlation between the front fixation time and the free throw hit rate, and there was a positive correlation between the top number of fixations and the free throw hit rate.

Microvasculature plays a crucial role in human physiology and is closely related to various human diseases. Building in vitro vascular networks is essential for studying vascular tissue behavior with repeatable morphology and signaling conditions. Engineered 3D microvascular network models, developed through advanced microfluidic-based techniques, provide accurate and reproducible platforms for studying the microvasculature in vitro, an essential component for designing organ-on-chips to achieve greater biological relevance. By optimizing the microstructure of microfluidic devices to closely mimic the in vivo microenvironment, organ-specific models with healthy and pathological microvascular tissues can be created. This review summarizes recent advancements in in vitro strategies for constructing microvascular tissue and microfluidic devices. It discusses the static vascularization chips’ classification, structural characteristics, and the various techniques used to build them: growing blood vessels on chips can be either static or dynamic, and in vitro blood vessels can be grown in microchannels, elastic membranes, and hydrogels. Finally, the paper discusses the application scenarios and key technical issues of existing vascularization chips. It also explores the potential for a novel organoid chip vascularization approach that combines organoids and organ chips to generate better vascularization chips.

Objective: To investigate the association between systemic immune inflammation index (SII) and all-cause or cardiovascular diseases (CVDs) mortality in US adults with different diabetic status based on the National Health and Nutrition Examination Survey (NHANES) database. Study design and setting: Adults with follow-up data in the NHANES 1999–2018 cycles were included in this study. The SII was calculated based on blood cells counts (including neutrophils, lymphocytes, and platelets) measured in the laboratory data. According to the quartiles of SII, population were divided into four groups (Q1-Q4). Mortality data was determined by linking NHANES survey participants to the National Death Index records, which collect mortality data and determine their vital status. Cox regression models were also performed to explore the hazard ratio (HR) and the corresponding 95 % confidence interval (95 % CI) of SII related with all-cause and CVDs mortality. In addition, restricted cubic spline was used to explore the nonlinear relationship between SII and mortality. Subgroup analysis and sensitivity analysis were performed to confirm the robustness of our results. Results: In this study, there were 45,454 participants were enrolled (50.43 % females), with a mean age of 47.35 ± 0.19 years. Among of which, 7971 were diabetes patients and 3281 were pre-diabetes. With the mean 9.89 ± 0.08 follow-up years, there were 6935 (15.26 %) deaths occurred. Of which, 1795 deaths were caused by CVDs. The age-adjusted death rates were higher in participants with high SII levels compared to those with low SII levels. Cox regression analysis, after adjusting for covariates, revealed that SII levels were associated with an increased risk of all-cause mortality (HR, 1.02; 95 % CI, 1.02–1.03, P

The excellent performance of deep neural networks on image classification tasks depends on a large-scale high-quality dataset. However, the datasets collected from the real world are typically biased in their distribution, which will lead to a sharp decline in model performance, mainly because an imbalanced distribution results in the prior shift and covariate shift. Recent studies have typically used a two-stage learning method consisting of two rebalancing strategies to solve these problems, but the combination of partial rebalancing strategies will damage the representational ability of the networks. In addition, the two-stage learning method is of little help in addressing the problem of covariate shift. To solve the above two issues, we first propose a sample logit-aware reweighting method called (SLA), which can not only repair the weights of majority class hard samples and minority class samples but will also integrate with logit adjustment to form a stable two-stage learning strategy. Second, to solve the covariate shift problem, inspired by ensemble learning, we propose a multi-domain expert specialization model, which can achieve a more comprehensive decision by averaging expert classification results from multiple different domains. Finally, we combine SLA and logit adjustment into a two-stage learning method and apply our model to the CIFAR-LT and ImageNet-LT datasets. Compared with the most advanced methods, our experimental results show excellent performance.

Ferroptosis is a regulatory cell death (RCD) caused by iron-dependent lipid peroxidation, which is the backbone of regulating various diseases such as tumor, nervous system diseases and so on. Despite ferroptosis without specific detection methods currently, there are numerous types of detection technology commonly used, including flow cytometry, cell activity assay, microscopic imaging, western blotting, quantitative polymerase chain reaction (qPCR). In addition, ferroptosis could be detected by quantifying oxygen-free radicals reactive oxygen species (ROS), the lipid metabolite (malondialdehyde ((MDA)), related pathways and observing mitochondrial damage. In the face of numerous detection methods, how to choose appropriate detection methods based on experimental purposes has become a problem that needs to be solved at present. In this review, we summarized the commonly used detection methods of the critical substances in the process of ferroptosis, in the hope of facilitating the comprehensive study of ferroptosis, with a view to providing a guidance for subsequent related research.

Colorectal cancer (CRC) is the most prevalent cancer of the digestive tract. Herba Patriniae (also known as Bai Jiang Cao, HP) have been widely used to manage diarrhea, ulcerative colitis, and several cancers, including CRC. Nonetheless, the molecular mechanisms underlying the pharmacological action of HP on CRC remain unclear. This study investigated the underlying mechanisms of HP against CRC using network pharmacology analysis and in vitro and in vivo experiments. The results revealed nine bioactive compounds of HP. Furthermore, 3460 CRC-related targets of the identified active compounds were predicted from the Gene Expression Omnibus (GEO) database. Furthermore, 65 common targets were identified through the intersection of two related targets. Moreover, ten hub genes, including CDK4, CDK2, CDK1, CCND1, CCNB1, CCNA2, MYC, E2F1, CHEK1, and CDKN1A were identified through the topological analysis. Meanwhile, the GO and KEGG pathway analysis revealed that the core target genes were majorly enriched in the p53 and HIF-1 signaling pathways. Moreover, HP promoted apoptosis and suppressed cell proliferation by activating the p53 signaling pathway in a dose-dependent manner, while a similar effect was observed for Isovitexin (the primary component of HP). Overall, this study provides valuable insights into the underlying mechanisms of HP and its component Isovitexin against CRC, providing a theoretical foundation for additional experimental verification of its clinical application.

ObjectiveKlebsiella pneumoniae (Kp) bloodstream infections (BSI) can be a life-threatening opportunistic infection. We aimed to evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) for Kp BSI.MethodsWe retrospectively analyzed 72 patients suspected with bloodstream infection and mNGS Kp positive in peripheral blood, who were hospitalized in our hospital from January 2022 to January 2023. Clinical data and laboratory parameters were collected. All patients had blood drawn and other samples for blood mNGS, blood cultures (BC) and other cultures (OC). The accuracy of mNGS results was analyzed according to infection site, clinical indicators, therapeutic effect and routine culture results. The detection of pathogenic microorganisms by blood mNGS and routine culture was compared.ResultsAmong 72 infection patients, 29 cases (40.28%) were BC positive, 43 cases (59.72%) were other culture (OC) positive, 16 cases (22.22%) were both BC and OC positive, 56 cases were positive for both mNGS and routine culture. Among the 56 double-positive cases, mNGS and conventional cultures were completely consistent in 27 cases, partially consistent in 15 cases, and completely inconsistent in 14 cases. Using the clinical diagnosis as the reference standard, There were 51 cases consistent with the results of mNGS with Kp BSI, the clinical consistency was 70.83% (51/72). The coincidence rate of mNGS and clinical diagnosis was higher than that of BC (54.17%, 39/72), indicating a statistically significant difference between the two methods (P

Abstract Chimeric antigen receptor (CAR) T cells have been successfully used in adoptive cell therapy for malignancies. However, some obstacles, including side effects such as graft‐versus‐host disease and cytokine release syndrome, therapy resistance, limited sources, as well as high cost, limited the application of CAR T cells. Recently, CAR natural killer (NK) cells have been pursued as the effector cells for adoptive immunotherapy for their attractive merits of strong intrinsic antitumor activity and relatively mild side effects. Additionally, CAR NK cells can be available from various sources and do not require strict human leukocyte antigen matching, which suggests them as promising “off‐the‐shelf” products for clinical application. Although the use of CAR NK cells is restrained by the limited proliferation and impaired efficiency within the immunosuppressive tumor microenvironment, further investigation in optimizing CAR structure and combination therapies will overcome these challenges. This review will summarize the advancement of CAR NK cells, CAR NK cell manufacture, the clinical outcomes of CAR NK therapy, the challenges in the field, and prospective solutions. Besides, we will discuss the emerging application of other immune cells for CAR engineering. Collectively, this comprehensive review will provide a valuable and informative summary of current progress and evaluate challenges and future opportunities of CAR NK cells in tumor treatment.

IntroductionThe chronological age (CA) cannot precisely reflect the health status. Our study aimed to establish a model of kidney biological age to evaluate kidney function more elaborately.MethodsThe modeling group was used to establish the model, consisting of 1,303 respondents of the China Health and Retirement Longitudinal Study (CHARLS). The biological age of the kidney (BA) was constructed by principal component analysis (PCA) and Klemera and Doubal’s method (KDM) with the 1,303 health respondents.ResultsPCA was chosen as the best method for our research step by step. The test group was used to apply the model. (a) BA of the kidney can distinguish respondents with from without kidney disease. (b) BA of the kidney was significantly different in various levels of kidney function. The BA of the eGFR

Summary: Accurate risk stratification for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is crucial for prognosis and treatment decisions. Here, we develop a tumor microenvironment-associated circular RNA (circRNA) signature that can stratify LA-NPC patients with different risks of relapse and vulnerability to induction chemotherapy (IC). Relapsed-related circRNAs are identified by comparing expression profiles between patients with and without relapse, followed by quantitative validation in the training cohort (n = 170). A nine-circRNA signature is constructed to classify patients into high-risk and low-risk groups. Low-risk patients have significantly favorable clinical survivals, which is validated in the internal (n = 170) and external (n = 150) cohorts. They are characterized by an immune-active microenvironment and can derive benefits from IC. Meanwhile, high-risk patients characterized with pro-relapse and DNA repair-associated features, are vulnerable to chemoresistance. Overall, the circRNA-based classifier serves as a reliable prognostic tool and might guide chemotherapy decisions for patients with LA-NPC.

Leptin is a peptide hormone that regulates energy balance, immune inflammatory response, and bone metabolism. Several studies have demonstrated a relationship between leptin and periodontitis, a local inflammatory disease that progressively weakens the supporting structures of the teeth, eventually leading to tooth loss. This article reviews the existing literature and discusses leptin’s basic characteristics, its relationship with periodontitis, and its effects on periodontal tissue metabolism.

Prevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires in vivo evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1, B8-dIgA2 and TH335-dIgA1 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparable neutralization potency against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viral loads in lungs significantly, prophylactic intranasal B8-dIgA unexpectedly led to high amount of infectious viruses and extended damage in NT compared to controls. Mechanistically, B8-dIgA failed to inhibit SARS-CoV-2 cell-to-cell transmission, but was hijacked by the virus through dendritic cell-mediated trans-infection of NT epithelia leading to robust nasal infection. Cryo-EM further revealed B8 as a class II antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Neutralizing dIgA, therefore, may engage an unexpected mode of SARS-CoV-2 nasal infection and injury.

AbstractBackground The treatment of refractory nephrotic syndrome (RNS) is full of challenges and the role of rituximab (RTX) is not well-established, thus this study aims to demonstrate the role of RTX in RNS.Methods This was a multicenter retrospective study of all adult patients receiving RTX for RNS. Patients enrolled were divided into two groups according to pathological pattern: 20 patients as a group of podocytopathy (including minimal change disease [MCD] and focal and segmental glomerulosclerosis [FSGS]), and 26 patients as membranous nephropathy (MN) group. The remission rate, relapse rate, adverse effects, and predictors of remission were analyzed.Results A total of 75 patients received RTX for RNS and 48 were available for analysis after exclusion criteria. No significant difference in the remission rate at 6 or 12 months was observed between the MCD/FSGS and MN cases (p > 0.05). The median duration of the first complete remission (CR) was 1 month in the podocytopathy group and 12.5 months in the MN group. Three relapses were associated with infection as the ultimate outcome, and 6 out of 48 remained refractory representing a response rate of 87.5% in RNS. Clinical predictors of cumulative CR were estimated glomerular filtration rate (eGFR)

ABSTRACTCandida auris has emerged as a serious threat of public health and caused global epidemic due to multi-drug resistance, remarkable transmissibility and high mortality. To tackle the challenging super fungus, novel benzoanilide antifungal agents were discovered by an integrated strategy of phenotypic screen, hit optimization, antifungal assays and mechanism exploration. The most promising compound A1 showed potent in vitro and in vivo efficacy against Candida auris infection. Mechanism investigation revealed that compound A1 blocked the biosynthesis of virulence factors and fungal cell walls through the inhibition of glycosylphosphatidylinositol (GPI) and GPI-anchored proteins. Thus, compound A1 represents a promising lead compound to combat drug-resistant candidiasis.

Bisphenol compounds (BPs) are one of the most significant raw materials, used in synthesizing high polymer materials. At present, common BPs mainly include bisphenol A, bisphenol B, bisphenol F, bisphenol AF and so on. Nowadays, BPs are principally applied in plastic products, the food packaging, drinking water additives, seafood and other fields. A large number of studies have found that BPs penetrate into human beings and animals by physical migration, chemical migration, biological migration and it even have been detected in deep-sea mammals, affecting the mechanisms of the reproductive system, central nervous system, digestive system, cardiovascular system, behavior, development, and metabolic diseases. Therefore, BPs have been attracting more attention. In the review, the classification, invasive pathway to foods of BPs, and its implication on human beings and animals are systematically reviewed, hoping to provide reference for the safety and toxicological evaluation of BPs.

Abstract γδ intestinal intraepithelial lymphocytes (IELs) constitute the majority of IELs with unique CD8αα+ homodimers that are distinct from γδT cells in other tissues. However, it remains largely unclear how those cells develop. Here we show that transforming growth factor beta (TGF-β) signaling controls the development of TCRγδ+CD8αα+ IELs. Deletion of TGF-β receptors or Smad3 and Smad2 in bone marrow stem cells caused a deficiency of TCRγδ+CD8αα+ IELs in mixed bone marrow chimeric mice. Mechanistically, TGF-β is required for the development of TCRγδ+CD8αα+ IELs thymic precursors (CD44–CD25– γδ thymocytes). In addition, TGF-β signaling induced CD8α in thymic γδT cells and maintained CD8α expression and survival in TCRγδ+CD8αα+ IELs. Moreover, TGF-β also indirectly controls TCRγδ+CD8αα+ IELs by modulating the function of intestinal epithelial cells (IECs). Importantly, TGF-β signaling in TCRγδ+CD8αα+ IELs safeguarded the integrity of the intestinal barrier in dextran sulfate sodium (DSS)-induced colitis.

Abstract Background Bronchopulmonary dysplasia (BPD) is the most common and serious chronic lung disease in preterm infants with pathological characteristics of arrested lung development. DNA double-strand breaks (DSBs) are a serious manifestation of oxidative stress damage, but little is known about the role of DSBs in BPD. The current study set out to detect DSB accumulation and cell cycle arrest in BPD and study the expression of genes related to DNA damage and repair in BPD through DNA damage signaling pathway-based PCR array to determine a suitable target to improve arrested lung development associated with BPD. Methods DSB accumulation and cell cycle arrest were detected in a BPD animal model and primary cells, then a DNA damage signaling pathway-based PCR array was used to identify the target of DSB repair in BPD. Results DSB accumulation and cell cycle arrest were shown in BPD animal model, primary type II alveolar epithelial cells (AECII) and cultured cells after exposure to hyperoxia. Of the 84 genes in the DNA damage-signaling pathway PCR array, eight genes were overexpressed and 11 genes were repressed. Rad1, an important protein for DSB repair, was repressed in the model group. Real-time PCR and western blots were used to verify the microarray results. Next, we confirmed that silencing Rad1 expression aggravated the accumulation of DSBs and cell cycle arrest in AECII cells, whereas its overexpression alleviated DSB accumulation and cell cycle arrest. Conclusions The accumulation of DSBs in AECII might be an important cause of alveolar growth arrest associated with BPD. Rad1 could be an effective target for intervention to improve this arrest in lung development associated with BPD.

Abstract Background Preemptive intercostal nerve block (pre-ICNB) achieves the same analgesic effects as postoperative ICNB (post-ICNB) remains unclear. This study aimed to evaluate the efficacy of preemptive ICNB on perioperative outcomes for patients undergoing video-assisted thoracic surgery (VATS). Methods This was a randomized, open-label study (ChiCTR2200055667) from August 1, 2021, to December 30, 2021. Eligible patients scheduled for lobectomy for lung cancer were allocated into the pre-ICNB group and the post-ICNB group. The postoperative pain evaluation, patient rehabilitation, and opioid consumption were observed. Results A total of 81 patients were included. When compared with the post-ICNB group, the pre-ICNB group had a lower proportion of hypertension comorbidity (P = 0.023), significantly lower total consumption of morphine milligram equivalents (MMEs) (P = 0.016), shorter extubation time (P = 0.019). The pre-ICNB group has similar Numeric Rating Scales (NRS) scores of dynamic pain in the post-anesthesia care unit (PACU), postoperative 6 h, 12 h, 24 h, and 48 h (P > 0.05), and had simialr scores of Bruggrmann Comfort Scale (BCS) in postoperative 6 h, 12 h, 24 and 48 h (P > 0.05). The scores of the Mini-mental state examination (MMSE) and Ramsay in the pre-ICNB group were comparable to those in the post-ICNB group, except the scores of MMSE and Ramsay in postoperative 6 h were lower (P = 0.048 and P = 0.019). The pain evaluation in the 1-month follow-up was comparable with that in the post-ICBN group (P > 0.05). Conclusions Pre- ICNB is equally efficacious in perioperative pain management as post-ICNB, and pre-ICNB significantly reduces intra-operative opioid consumption, providing faster recovery in PACU. Trial registration Registered in the Chinese Clinical Trial Register (ChiCTR2200055667).