Asiaticoside enhances the effect of propofol on the invasion, ferroptosis and immune escape of bladder cancer.

Bladder cancer is a highly prevalent malignancy. Asiaticoside (AC), a triterpenoid derivative, exhibits antitumor effect on different tumors. This study aimed to explore the role and mechanism of AC on bladder cancer. J82 and T24 cells were treated with AC and/or propofol, and nude mice were subcutaneously administrated with T24 cells. The effect and mechanism of AC and/or propofol were explored by cell counting kit-8, transwell, flow cytometry, enzyme-linked immunosorbent assay, immunohistochemistry and western blot assays both in vitro and in vivo. Cell viability of J82 and T24 cells was inhibited by AC with a IC50 value of 2.43 µM and 2.16 µM, and by propofol with a IC50 value of 42.51 µM and 48.37 µM, respectively. AC or propofol alone decreased cell proliferation, invasion, and immune escape with the increased ferroptosis, as well as downregulating the level of the PI3K/AKT pathway in both animal and cell experiments. The effect of propofol on the above-mentioned indicators was further enhanced with the co-treatment of AC in vitro and in vivo. Taken together, AC promoted the ameliorative effect of propofol on bladder cancer involved in PI3K/AKT pathway.

IFN-α affects Th17/Treg cell balance through c-Maf and associated with the progression of EBV- SLE.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease, of which the pathogens is remains obscure. Viral infection, particularly Epstein Barr viru (EBV) infection, has been considered a common pathogenic factor. This study suggests that c-Maf may be an important target in T cell differentiation during SLE progression, providing a potentially new perspective on the role of viral infection in the pathogenesis of autoimmune diseases. METHODS: Cytokines of EBV-infected SLE patients were measured by ELISA and assessed in conjunction with their clinical data. IFN-α, c-Maf, and the differentiation of Th17/Treg cells in SLE patients and MRL/LPR mice were analyzed using FCM, WB, RT-PCR, etc. Following the infection of cells and mice with EBV or viral mimic poly (dA:dT), the changes of the aforementioned indicators were investigated. The relationship among IFN-α, STAT3, c-Maf and Th17 cells was determined by si-RNA technique. RESULTS: Many SLE patients are found to be complicated by viral infections; Further, studies have demonstrated that viral infection, especially EBV, is involved in SLE development. This study showed that viral infections might promote IFN-α secretion, inhibit c-Maf expression by activating STAT3, increase Th17 cell differentiation, and lead to the immune imbalance of Th17/Treg cells, thus playing a role in the onset and progression of SLE. CONCLUSION: This study demonstrates that EBV infections may contribute to SLE development by activating STAT3 through IFN-α, inhibiting c-Maf, and causing Th17/Treg immune imbalance. Our work provided a new insight into the pathogenesis and treatment of SLE.

Mitochondrial-dependent oxidative phosphorylation is key for postnatal metabolic adaptation of alveolar macrophages in the lung.

Alveolar macrophages (AMs) seed in lung during embryogenesis and become mature in perinatal period. Establishment of acclimatization to environmental challenges is important, whereas the detailed mechanisms that drive metabolic adaptation of AMs remains to be elucidated. Here, we showed that energy metabolism of AMs was transformed from glycolysis prenatally to oxidative phosphorylation (OXPHOS) postnatally accompanied by up-regulated expression of mitochondrial transcription factor A (TFAM). TFAM deficiency disturbed mitochondrial stability and decreased OXPHOS, which finally impaired AM maintenance and function, but not AM embryonic development. Mechanistically, Tfam-deletion resulted in impaired mitochondrial respiration and decreased ATP production, which triggered endoplasmic reticulum (ER) stress to cause B cell lymphoma 2 ovarian killer (BOK) accumulation and abnormal distribution of intracellular Ca2+, eventually led to induce AM apoptotic death. Thus, our data illustrated mitochondrial-dependent OXPHOS played a key role in orchestrating AM postnatal metabolic adaptation.

Association of self-reported arthritis with depression, anxiety, and comorbid depression/anxiety among the older Chinese adults: A cross-sectional study.

BACKGROUND: Arthritis is relatively common among middle-aged and older people and is a significant public health problem. However, research on the relationship between arthritis and mental health in older populations is currently limited. METHODS: Data were obtained from the Chinese Longitudinal Healthy Longevity Survey. The 10-item Center for Epidemiologic Studies Depression Scale and 7-item Generalized Anxiety Disorder Scale were used to evaluate depressive and anxiety symptoms. Arthritis status was self-reported. Linear and logistic regression analyses were conducted to assess the impact of arthritis on depression, anxiety, and comorbid depression/anxiety symptoms. RESULTS: A total of 11,104 participants aged ≥65 years (mean age, 83.1 ± 11.1 years) were included in the analysis. We detected positive associations of arthritis with depression symptoms (adjusted odds ratio [OR]: 1.57, 95 % confidence interval [CI] 1.33 to 1.86), anxiety symptoms (adjusted OR: 1.48, 95 % CI: 1.15 to 1.90), and comorbid depression/anxiety symptoms (adjusted OR: 1.88, 95 % CI: 1.41 to 2.5) in the older adult population. Participants with arthritis had higher anxiety (adjusted linear regression coefficient: 0.43, 95 % CI: 0.24 to 0.63) and depression (adjusted linear regression coefficient: 0.87, 95 % CI: 0.57 to 1.14) scores compared with those without arthritis. In addition, there were no significant interaction effects between arthritis and participant characteristics on depression symptoms, anxiety symptoms, or comorbid depression/anxiety symptoms. CONCLUSIONS: Arthritis was positively associated with depression symptoms, anxiety symptoms, and comorbid depression/anxiety symptoms among older adults. Further cohort studies are needed to validate these associations.

Performance evaluation of rural water environment governance based on AHP: a case study of the Beitang River Basin.

Rural water environment governance in China still lacks a systematic and comprehensive assessment protocol to help analyze and improve such governance performance. The Analytic Hierarchy Process (AHP) method was employed in this study to build a governance assessment system that integrates ecological conditions, water pollution control, and public satisfaction. To cover these topics, the assessment system is composed of an indicator layer that is customized to rural water environment governance in China. The Beitang River, located in the rural region of Hangzhou, Zhejiang, China, was presented as a case study. Field investigation provided raw data for this assessment. A questionnaire survey was conducted to interview local residents on the governance performance. An additional survey with executives who played major roles in the governance was performed to reconstruct a water environment assessment on the Beitang River prior to the governance, in order to highlight the effects of the governance through contrast. The results showed consistency in the questionnaire survey and the assessment system. The AHP assessment system was able to reflect the improvement in the water quality, river ecology, and residential welfare after the governance, and suggested limits and future directions in the following upgrade programs for the river basin.

The evaluation of university management performance using the CS-RBM algorithm.

Amidst the ongoing higher education reforms in China, the escalated investments in colleges and universities underscore the need for an effective assessment of their performance to ensure sustainable development. However, traditional evaluation methods have proven time-consuming and labor-intensive. In response, a novel approach called CS-RBM (Crow Search Restricted Boltzmann Machine) prediction algorithm has been proposed for the educational management of these institutions. By integrating the CS algorithm and an enhanced RBM algorithm, this method facilitates the scoring of project performance indicators, bolstered by insights from user evaluation form reports. The comprehensive project performance is ultimately derived from this combination. Comparative analysis with the standard particle swarm optimization algorithm on public data sets demonstrates a remarkable 45.6% reduction in prediction errors and an impressive 34.7% increase in iteration speed using the CS-RBM algorithm. The accuracy of the tested data set surpasses 98%, validating the efficacy of the CS-RBM algorithm in achieving precise predictions and effective assessments. Consequently, this innovative approach exhibits promising potential for expediting and enhancing the performance evaluation of colleges and universities, contributing significantly to their sustainable development.

Hydride-doped Ag17Cu10 nanoclusters as high-performance electrocatalysts for CO2 reduction.

The atomically precise metal electrocatalysts for driving CO2 reduction reactions are eagerly pursued as they are model systems to identify the active sites, understand the reaction mechanism, and further guide the exploration of efficient and practical metal nanocatalysts. Reported herein is a nanocluster-based electrocatalyst for CO2 reduction, which features a clear geometric and electronic structure, and more importantly excellent performance. The nanocatalysts with the molecular formula of [Ag17Cu10(dppm)4(PhC≡C)20H4]3+ have been obtained in a facile way. The unique metal framework of the cluster, with silver, copper, and hydride included, and dedicated surface structure, with strong (dppm) and labile (alkynyl) ligands coordinated, endow the cluster with excellent performance in electrochemical CO2 reduction reaction to CO. With the atomically precise electrocatalysts in hand, not only high reactivity and selectivity (Faradaic efficiency for CO up to 91.6%) but also long-term stability (24 h), are achieved.

Pathogens are an important driving force for the rapid spread of symbionts in an insect host.

One of the biggest challenges for pathogens invading hosts is microbial symbionts but the role of pathogens in symbionts in nature is unknown. By tracking the dynamics of the entomopathogenic fungal Cordyceps javanica and symbionts in natural populations of the whitefly Bemisia tabaci from 2016 to 2021 across China, we reveal that Rickettsia, a newly invaded symbiont, is positively correlated with the pathogen in both frequency and density. We confirm that applying pathogen pressure can selectively drive Rickettsia to sudden fixation in whiteflies both in the laboratory and in the field. Furthermore, the driving force is elucidated by the Rickettsia-conferred suppression of pathogen infection quantity, proliferation and sporulation, acting as a potential barrier of onward transmission of the pathogen. These results show that pathogens are an important driving force for rapid shifts in host symbionts in the natural niche.

Risk factors for secondary epilepsy in children with complex febrile seizures and their effect on growth and development-a retrospective cohort study.

Background: Complex febrile seizures are prolonged and can cause neurologic abnormalities, leading to secondary epilepsy and affecting growth and development. At present, the mechanism of secondary epilepsy in children with complex febrile seizures is not clear, and this study aimed to explore the risk factors for secondary epilepsy in children with complex febrile seizures and analyze its effects on the growth and development of children. Methods: The data of 168 children with complex febrile seizures admitted to the Ganzhou Women and Children's Health Care Hospital between January 2018 and December 2019 were collected retrospectively and divided into a secondary epilepsy group (n=58) and control group (n=110) according to whether the children had secondary epilepsy or not. The differences in clinical features between the 2 groups were compared, and logistic regression analysis was used to explore the risk factors for secondary epilepsy in children with complex febrile seizures. A nomogram prediction model for secondary epilepsy in children with complex febrile seizures was established and verified using the R 4.0.3 statistical software, and the effect of secondary epilepsy on the growth and development of children was analyzed. Results: Multivariate logistic regression analysis showed that family history of epilepsy, generalized seizures, number of seizures, and duration of seizures were independent influencing factors of secondary epilepsy in children with complex febrile seizures (P<0.05). The dataset was randomly divided into a training set and a validation set, with a sample size of 84 in the training set and 84 in the validation set. The area under the receiver operating characteristic (ROC) curve of the training set was 0.845 (95% confidence interval: 0.756-0.934), and the area under the ROC curve of the validation set was 0.813 (95% confidence interval: 0.711-0.914). Compared with the control group, the Gesell Development Scale score in the secondary epilepsy group was significantly reduced (77.84±8.86 vs. 85.64±8.65, P<0.001). Conclusions: The nomogram prediction model could better identify complex febrile seizures children at high risk of secondary epilepsy. Strengthening intervention in such children may be beneficial for improving their growth and development.

MiR-223-3p Aggravates Ocular Inflammation in Sjögren's Syndrome.

BACKGROUND AND OBJECTIVES: Sjogren's syndrome (SS) is a chronic autoimmune disease, particularly involving the lacrimal and salivary glands, with dryness as the main symptom. To date, the pathogenesis of SS is not fully understood. Recently, numerous miRNAs were implicated in SS etiology and pathogenesis. METHODS: Ocular wash was collected from SS patients and healthy controls. INF-γ-treated salivary gland epithelial cells (SGECs) were utilized as SS in vitro models. Expressions of miR-223-3p and inositol 1,4,5-trisphosphate receptor type 3 (ITPR3) in ocular wash specimens and cells were measured by RT-qPCR assay and western blot analysis, respectively. ELISA assay was exploited to detect IL-6, IL-12, and TNF-γ levels. CCK-8, flow cytometry, and western blot assay were exploited to determine cell viability, apoptosis, and apoptosis-related protein levels. RESULTS: ITPR3 was a direct downstream gene of miR-223-3p and negatively modulated by miR-223- 3p. MiR-223-3p increased while ITPR3 decreased in samples from SS patients and INF-γ-induced SGECs. miR-223-3p knockdown facilitated INF-γ-induced SGECs cell viability and restrained apoptosis and inflammation response through the NF-κB pathway. CONCLUSION: MiRNA-223-3p is implicated in the process of SS initiation and development. It may become one of the targets for the treatment of SS in the future, as well as a possible indicator for clinical monitoring of disease activity.

Evaluating the effects of nanoparticles combined ultrasonic-microwave thawing on water holding capacity, oxidation, and protein conformation in jumbo squid (Dosidicus gigas) mantles.

Magnetic nanoparticles (MNPs) have a dual role in acting as magnetic and sonosensitizer agents, which can combine the synergistic effects of microwave and ultrasonic waves. To study the effects of MNPs combined ultrasonic-microwave thawing (NUMT) on the water holding capacity (WHC), oxidation of protein and lipid, and protein conformation, jumbo squid mantles were subjected to cold storage thawing (CST), MNPs combined ultrasonic thawing (NUT), MNPs combined microwave thawing (NMT) and NUMT. Results showed that NUMT treatment had a higher WHC, lower oxidation, effectively reduced myofibrillar protein aggregation and degradation, and stabilized the structure of the protein of the jumbo squid. The muscle fiber structure of NUMT treated jumbo squid mantles was dense, orderly with a smooth surface, and the fiber network gaps were small and uniformly distributed. This study shows that NUMT can ameliorate the thawing qualities of jumbo squid, and is an effectively thawing method.

Comparison of short interval and low dose (SILD) with high dose of cyclophosphamide in the susceptibility to infection in SLE: a multicentrereal-world study.

OBJECTIVE: Infection is a major cause of death in patients with SLE. This study aimed to explore the infection rate in patients with SLE receiving a low dose of intravenous cyclophosphamide (IV-CYC). METHODS: Clinical parameters of 1022 patients with SLE from 24 hospitals in China were collected. Patients were divided into the short-interval and lower-dose (SILD, 400 mg every 2 weeks) IV-CYC group and the high-dose (HD, 500 mg/m2 of body surface area every month) IV-CYC group. The clinical data and infection rate between the two groups were compared. RESULTS: Compared with HD IV-CYC, the infection rate of the SILD IV-CYC group was significantly lower (13.04% vs 22.27%, p=0.001). Respiratory tract infection (10.28% vs 15.23%, p=0.046) and skin/soft tissue infection (1.78% vs 4.3%, p=0.040) were significantly decreased in the SILD IV-CYC group. Moreover, infections occurred most likely in patients with SLE with leucopenia (OR 2.266, 95% CI 1.322 to 3.887, p=0.003), pulmonary arterial hypertension (OR 2.756, 95% CI 1.249 to 6.080, p=0.012) and >15 mg/day of glucocorticoid (OR 2.220, 95% CI 1.097 to 4.489, p=0.027). CONCLUSIONS: SILD IV-CYC showed a lower frequency of infection events than high-dose IV-CYC in patients with SLE.

What we bet on is not only tangible money, but also good mood.

A surprisingly large number of lottery prizes go unclaimed every year. This leads us to suspect that what people bet on is not only money, but also good mood. We conducted three studies to explain, from an emotional perspective, why people play lottery games. We first conducted two survey studies to assess mood state reported by online (Study 1a) and offline lottery buyers (Study 1b) at different stages of lottery play. The results revealed that participants' highest mood appeared before knowing whether they had won. In Study 2, we manipulated the means of reward (lottery tickets vs. cash) and compared participants' mood changes at different stages of a rewards game in the laboratory. We found the following: first, lottery group participants were generally in a better mood; second, 42% of lottery group participants did not come to the laboratory to collect scratch cards; and third, lottery group participants took more time to return to the laboratory to check their tickets than participants in the cash group. In Study 3, we examined whether priming good or bad mood could influence participants' preferences for cash versus lottery tickets. The results revealed that participants who were primed for poor mood had a higher preference for lottery tickets compared with their good mood counterparts. These findings suggest that what our participants sought in lottery play was not only money, but improved mood.

Attitudes toward COVID-19 Vaccination: A Survey of Chinese Patients with Rheumatic Diseases.

The coronavirus disease 2019 (COVID-19) pandemic has imposed enormous morbidity and mortality burdens. Patients with rheumatic diseases (RDs) are vulnerable to the COVID-19 infection, given their immunocompromised status. Ensuring acceptance of the COVID-19 vaccine is important and has attracted attention by health professionals. In this study, we designed an online cross-sectional survey that used an online questionnaire from 8 May 2021 to 4 October 2021. Attitudes toward the COVID-19 vaccination, personal information, current disease activity status, adverse events (AEs), and knowledge sources of vaccines were collected. Descriptive statistics, nonparametric tests, and ordinal logistic regression were used to analyze the data. A total of 1022 questionnaires were received, among which 70.2% (720/1022) of patients with RDs agreed to vaccination, while only 31.6% of patients were actually vaccinated. Male, employed, high-income patients and those with inactive disease showed a more positive attitude. Concerns of AEs and disease flare were the main factors affecting vaccination willingness. Only 29.6% (304/1022) of patients thought they had received enough information about the COVID-19 vaccine from their doctors. In conclusion, most patients with RDs in China intended to get vaccinated, although the vaccination rate in this particular population was low. Rheumatologists should take more responsibility in COVID-19 vaccination education of patients with RDs.

Bt protein hasten entomopathogenic fungi-induced death of nontarget pest whitefly by suppressing protective symbionts.

The risk assessment of Bacillus thuringiensis (Bt) crops on nontarget pests has received much attention. Despite the knowledge of various beneficial bacterial symbionts in pests, whether Bt proteins affect these symbionts and subsequently alter the pest's ecology remains largely unknown. The whitefly Bemisia tabaci is one of the most serious nontarget pests in Bt cotton. Here, we explored the Bt Cry1Ac protein-induced changes in whitefly symbiont abundance and the subsequent effects on whitefly response against a naturally prevalent entomopathogenic fungus Cordyceps javanica. The obligate symbiont 'Candidatus Portiera aleyrodidarum' (hereafter P. aleyrodidarum) as well as facultative symbionts 'Candidatus Hamiltonella defensa' (hereafter H. defensa), 'Candidatus Cardinium hertigii' (hereafter C. hertigii) and 'Candidatus Rickettsia bellii' (hereafter R. bellii) dominate the microbial community of whiteflies. The Bt exposure had no effects on H. defensa infected (H) and H. defensa-C. hertigii doubly infected (HC) whiteflies, but decreased the total copy number of symbionts as well as the R. bellii proportion in H. defensa-C. hertigii- R. bellii triply infected whiteflies (HCR). C. javanica caused whitefly adults 100 % mortality within 8 days. Without Bt protein exposure, HCR whiteflies survived significantly longer than H and HC whiteflies sprayed by C. javanica, suggesting that R. bellii confers protection. However, in Bt-exposed groups, C. javanica generated synchronous death of H, HC and HCR whiteflies. Specifically, in H and HC whiteflies, Bt protein-exposure showed no significant difference in progress of death caused by C. javanica. But in HCR whiteflies, Bt exposure hastened death induced by C. javanica, suppressing the R. bellii-conferred protection. This is the first report revealing that Bt protein altered symbiont community conferred adverse effects on nontarget pests, providing a new perspective for Bt risk assessment and biocontrol strategies of nontarget pests.

The Roles of Ciliary Neurotrophic Factor - from Neuronutrition to Energy Metabolism.

Ciliary neurotrophic factor (CNTF) is a pluripotent neurotrophic factor originally isolated from chicken embryo ciliary neurons. It has a powerful role in developing and maintaining the optic nervous system and has been used for many vision-related diseases. It also plays an important role in the neurogenesis, regeneration and survival of other neurons, including neural stem cells, dorsal root ganglion, sensory neurons and motor neurons. CNTF is related to neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. In addition to its role in the nervous system, CNTF regulates the balance of energy metabolism and the administration of CNTF induces body weight loss. More CNTF functions have been found with the deepening of study, such as protecting and promoting cardiomyocyte proliferation. In addition, CNTF even participates in mental illness and inflammation suppressing. CNTF exerts multidirectional physiological activity by regulating the transcription of various genes through a variety of signalling pathways (including JAK/STAT, MAPK, and PI3K/AKT). This review summarizes the roles and mechanisms of CNTF in the optic nervous system, retinal-related diseases, neuronal protection, and especially nutrition, energy metabolism and other aspects.

Integrated gene co-expression network analysis reveals unique developmental processes of Aurelia aurita.

The typical life cycle of the moon jellyfish (Aurelia aurita) includes the planula, polyp, strobila, ephyra, and medusa developmental stages. These stages exhibit huge differences in both external morphology and internal physiological functions. However, the gene co-expression network involved in these post-embryonic developmental processes has not been studied yet. Here, based on 15 RNA sequencing samples covering all five stages of the A. aurita life cycle, we systematically analyzed the gene co-expression network and obtained 35 relevant modules. Furthermore, we identified the highly correlated modules and hub genes for each stage. These hub genes are implicated to play important roles in the developmental processes of A. aurita, which should help improve our understanding of the jellyfish life cycle.

CircRTN4 aggravates mesangial cell dysfunction by activating the miR-513a-5p/FN axis in lupus nephritis.

Circular RNAs (circRNAs) are regulators of gene expression that can regulate cell proliferation and programmed cell death and serve as biomarkers in renal diseases. However, the specific traits and underlying mechanisms of circRNAs in the progression of lupus nephritis (LN) have not been elucidated. In the present study, we clarified that hsa_circ_0054595 (circRTN4) was upregulated in human renal mesangial cells (HRMCs). In cultured HRMCs, circRTN4 could enhance FN expression by directly interacting with miR-513a-5p. High circRTN4 expression in monocytes disseminated into HRMCs in an exosomal manner, thereby accelerating cell proliferation and extracellular matrix deposition. In addition, knockdown of circRTN4 in the kidney or peripheral blood alleviated renal damage in MRL/lpr and BALB/c mice. Clinically, high levels of circRTN4 were found in peripheral blood mononuclear cells and kidney tissues of LN patients, hence serving as an effective biomarker for LN detection and a novel therapeutic target. Our findings indicated that circRTN4 exacerbates mesangial cell dysfunction by activating the miR-513a-5p/FN axis in lupus nephritis.

Erratum: circRNA Mediates Silica-Induced Macrophage Activation Via HECTD1/ZC3H12A-Dependent Ubiquitination: Erratum.

[This corrects the article DOI: 10.7150/thno.21648.].