"Ping-pong" in the heart: a case report and literature review.

BACKGROUND: Ball thrombus is rare and life-threatening. The correct diagnosis and timely management are key to improving patient prognosis. Here, we present a case report and literature review of ball thrombus. CASE PRESENTATION: A 75-year-old woman presented to our outpatient clinic because of palpitations and chest distress for 8 months. She was diagnosed mitral stenosis, and transthoracic echocardiography (TTE) showed a round mass attached to the left atrial (LA) wall. Before anesthesia induction, TTE found that the mass has dropped from the LA wall, and was spinning in the LA causing intermittent obstruction of the valve. Anesthesia induction was then carried out under TTE monitoring, and transesophageal echocardiograph found another mass in the LA appendage after intubation. She underwent LA mass removal and mitral valve replacement, and was discharged uneventfully. Histopathology confirmed the diagnosis of thrombus. Our literature review identified 19 cases of ball thrombus between 2015 and 2024. The average age was 54.8 (range 3-88) years. Heart failure was present as the initial symptom in 11 cases, and most patients had mitral valve disease or concomitant with atrial fibrillation. 12 cases received surgery, and 7 received medical treatment only. 2 deaths occurred, one due to the obstruction of left ventricular inflow tract and the other due to the worsening of heart failure. CONCLUSION: Ball thrombus is rare in clinical settings. Urgent thrombectomy should be performed as soon as possible, and echocardiography can be used for real-time monitoring during surgery.

Insights into the molecular network characteristics of major HIV-1 subtypes in developed Eastern China: a study based on comprehensive molecular surveillance data.

PURPOSE: This study aimed to conduct a comprehensive molecular epidemiology study of major HIV-1 subtypes in developed Eastern China (Zhejiang Province). METHODS: Plasma samples and epidemiological information were collected from 4180 newly diagnosed HIV-1 positive patients in Zhejiang Province in 2021. Pol sequences were obtained to determine the subtypes via multiple analytical tools. HIV-1 molecular networks were constructed on the basis of genetic distances to analyze transmission patterns among major subtypes. Furthermore, the birth-death skyline (BDSKY) model was utilized to estimate the transmission risks associated with large clusters (LCs). RESULTS: In 4180 patients, 3699 (88.49%) pol sequences were successfully obtained and classified into four subtype groups. In the networks under an optimal genetic distance of 0.01 substitutions/site, the majority of links (74.52%, 1383/1856) involved individuals within the same city, highlighting the predominant role of local transmission in driving the HIV-1 epidemic. In the CRF07_BC, CRF01_AE, and others/URFs networks, men who have sex with men (MSM) were the primary sexual transmission population, with the younger MSM group (< 30 years old) exhibiting higher linkage frequencies. Within the CRF08_BC network, 93.98% of individuals were infected primarily through heterosexual contact and had a significantly greater risk of localized clustering than other subtypes did. Moreover, fifteen identified LCs were predominantly transmitted through commercial heterosexual contact (CHC), exhibiting localized clustering and high potential for sustained diffusion. CONCLUSIONS: Overall, our findings reveal a diverse and heterogeneous distribution of HIV-1 subtypes in Zhejiang Province, with noticeable variations in hotspots across different geographic areas and populations.

[Prediction of color simulation prescription for traditional Chinese medicine placebo solution based on whale algorithm-optimized back propagation neural network].

Traditional Chinese medicine(TCM) placebos are simulated preparations for specific objects and the color simulation in the development of TCM placebos is both crucial and challenging. Traditionally, the prescription screening and pattern exploration process involves extensive experimentation, which is both time-consuming and labor-intensive. Therefore, accurate prediction of color simulation prescriptions holds the key to the development of TCM placebos. In this study, we efficiently and precisely predict the color simulation prescriptions of placebos using an image-based approach combined with Matlab software. Firstly, images of TCM placebo solutions are captured, and 13 chromaticity space values such as the L* a* b*, RGB, HSV, and CMYK values are extracted using Photoshop software. Correlation analysis and normalization are then performed on these extracted values to construct a 13×9×3 back propagation(BP) neural network model. Subsequently, the whale optimization algorithm(WOA) is employed to optimize the initial weights and thresholds of the BP neural network. Finally, the optimized WOA-BP neural network is validated using three representative instances. The training and prediction results indicate that, compared to the BP neural network, the WOA-BP neural network demonstrates superior performance in predicting the pigment ratios of placebos. The correlation coefficients for training, validation,testing, and the overall dataset are 0. 95, 0. 87, 0. 95, and 0. 95, respectively, approaching unity. Furthermore, all error values are reduced, with the maximum reduction reaching 99. 83%. The color difference(ΔE) values for the three validation instances are all less than 3, further confirming the accuracy and practicality of the WOA-BP neural network approach.

Transcriptome analysis reveals EBF1 ablation-induced injuries in cardiac system.

Rationale: Regulatory processes of transcription factors (TFs) shape heart development and influence the adult heart's response to stress, contributing to cardiac disorders. Despite their significance, the precise mechanisms underpinning TF-mediated regulation remain elusive. Here, we identify that EBF1, as a TF, is highly expressed in human heart tissues. EBF1 is reported to be associated with human cardiovascular disease, but its roles are unclear in heart. In this study, we investigated EBF1 function in cardiac system. Methods: RNA-seq was utilized to profile EBF1 expression patterns. CRISPR/Cas9 was utilized to knock out EBF1 to investigate its effects. Human pluripotent stem cells (hPSCs) differentiated into cardiac lineages were used to mimic cardiac development. Cardiac function was evaluated on mouse model with Ebf1 knockout by using techniques such as echocardiography. RNA-seq was conducted to analyze transcriptional perturbations. ChIP-seq was employed to elucidate EBF1-bound genes and the underlying regulatory mechanisms. Results: EBF1 was expressed in some human and mouse cardiomyocyte. Knockout of EBF1 inhibited cardiac development. ChIP-seq indicated EBF1's binding on promoters of cardiogenic TFs pivotal to cardiac development, facilitating their transcriptional expression and promoting cardiac development. In mouse, Ebf1 depletion triggered transcriptional perturbations of genes, resulting in cardiac remodeling. Mechanistically, we found that EBF1 directly bound to upstream chromatin regions of cardiac hypertrophy-inducing genes, contributing to cardiac hypertrophy. Conclusions: We uncover the mechanisms underlying EBF1-mediated regulatory processes, shedding light on cardiac development, and the pathogenesis of cardiac remodeling. These findings emphasize EBF1's critical role in orchestrating diverse aspects of cardiac processes and provide a promising therapeutic intervention for cardiomyopathy.

Unravelling oncosis: morphological and molecular insights into a unique cell death pathway.

Programmed cell death (PCD) is a fundamental biological process for maintaining cellular equilibrium and regulating development, health, and disease across all living organisms. Among the various types of PCD, apoptosis plays a pivotal role in numerous diseases, notably cancer. Cancer cells frequently develop mechanisms to evade apoptosis, increasing resistance to standard chemotherapy treatments. This resistance has prompted extensive research into alternative mechanisms of programmed cell death. One such pathway is oncosis, characterized by significant energy consumption, cell swelling, dilation of the endoplasmic reticulum, mitochondrial swelling, and nuclear chromatin aggregation. Recent research suggests that oncosis can impact conditions such as chemotherapeutic cardiotoxicity, myocardial ischemic injury, stroke, and cancer, mediated by specific oncosis-related proteins. In this review, we provide a detailed examination of the morphological and molecular features of oncosis and discuss various natural or small molecule compounds that can induce this type of cell death. Additionally, we summarize the current understanding of the molecular mechanisms underlying oncosis and its role in both normal physiology and pathological conditions. These insights aim to illuminate future research directions and propose innovative strategies for leveraging oncosis as a therapeutic tool against human diseases and cancer resistance.

Impact Assessment of the "4+1 Nursing Operation Mode" on Enhancing the Efficacy of Alveolar Surgery Diagnosis and Treatment.

OBJECTIVE: The aim of this study is to evaluate the impact of the "4+1 Nursing Operation Mode" on improving the efficacy of alveolar surgery and the effectiveness of nursing. METHODS: A total of 200 patients were recruited from the oral and maxillofacial surgery outpatient department at the School and Hospital of Stomatology, Wuhan University, between November and December 2023. These patients were allocated into 2 groups: a control group and an experimental group. The treatment for these groups involved different combinations of physicians and nurses, including doctors A and B, and nurses A, B, and C. In November 2023, doctor A treated 50 patients with the assistance of nurses A and C under the "4+1 Nursing Operation Mode," while another 50 patients were treated by doctor A with the assistance of nurse A following the "Four-Handed Operation Mode." In December 2023, doctor B treated 50 patients with the assistance of nurse B under the "Four-Handed Operation Mode," and another 50 patients were treated by doctor B with the assistance of nurses B and C using the "4+1 Nursing Operation Mode." Patient visit durations were documented, and patient satisfaction with diagnostic and treatment services was evaluated via a questionnaire survey. RESULTS: In comparison to the "Four-Handed Operation Mode," the "4+1 Nursing Operation Mode" resulted in a 27% reduction in patient visit times and an improvement in patient satisfaction with nursing services. CONCLUSIONS: The "4+1 Nursing Operation Mode" surpasses the "Four-Handed Operation Mode" in terms of efficiency. It not only reduces patient visit times and enhances doctor work efficiency but also improves patient satisfaction with nursing services.

Influence of dental implant clinical experience on the accuracy of robot-assisted immediate implant placement: an in vitro study.

OBJECTIVES: To assess the accuracy and effectiveness among operators with different levels of experience in a robot-assisted immediate implant surgery. MATERIALS AND METHODS: The study included four participants who had received dental training at the same institution but have varying levels of clinical experience in implant dentistry, denoted as undergraduate student (UG), dental resident (DR), specialist with no robot experience (IS) and specialist with robot experience (RS). Following comprehensive theoretical training in robot-assisted implant operation, each operator participated in five robotic-assisted implant procedures at 21 sites, resulting in the implant surgery of a total of 20 implants. Subsequently, the accuracy of the implants was assessed by analyzing the preoperative planning and the postoperative CBCT scans, and the time required for each procedure was also recorded. RESULTS: Angular deviation in UG, DR, IS and RS group was 0.82 ± 0.27°, 0.55 ± 0.27°, 0.83 ± 0.27°, and 0.56 ± 0.36°, respectively. The total deviation of the implant platform point was 0.28 ± 0.10 mm, 0.26 ± 0.16 mm, 0.34 ± 0.08 mm and 0.31 ± 0.06 mm, respectively. The total deviation of the apical point was 0.30 ± 0.08 mm, 0.25 ± 0.18 mm, 0.31 ± 0.09 mm, and 0.31 ± 0.05 mm, respectively. The time spent was 10.37 ± 0.57 min, 10.56 ± 1.77 min, 9.93 ± 0.78 min, and 11.76 ± 0.78 min for each operator. As the number of operations increased, the operation time decreased, but there was no significant difference in implant accuracy between the different groups. CONCLUSIONS: Within the scope of this study, robot-assisted implant surgery demonstrated high accuracy, with no significant differences in performance between operators with varying levels of clinical experience or implant robot-user experience. Furthermore, the learning curve for robotic implant surgery is steep and consistent. CLINICAL RELEVANCE: Robot-assisted implant surgery demonstrates consistent high accuracy across operators of varying clinical and robotic experience levels, highlighting its potential to standardize procedures and enhance predictability in clinical outcomes.

A Nomogram for Predicting Postoperative Pulmonary Complications in Critical Patients Transferred to ICU After Abdominal Surgery.

OBJECTIVE: The purpose of this study was to investigate the risk factors associated with postoperative pulmonary complications(PPCs) in critically ill patients transferred to intensive care unit(ICU) after abdominal surgery and develop a predictive model for this disease. METHODS: Data for 3716 patients who were admitted to ICU after abdominal surgery in Peking University People's Hospital between January 2015 and December 2020 were retrospectively collected and analyzed to identify the risk factors and develop a nomogram prediction model. Data for patients admitted to ICU following abdominal surgery at Peking University People's Hospital from March 2021 to December 2022 were prospectively collected as a validation set to validate and assess the model. RESULTS: 10 independent risk factors for PPCs in critically ill patients transferred to ICU after abdominal surgery were identified. A nomogram prediction model was constructed for PPCs in this group patients, the area under ROC curve was 0.771[95%CI: 0.756,0.786] and 0.759[95%CI: 0.726,0.792] in the training set and validation set, respectively. CONCLUSIONS: In this study, independent risk factors for PPCs in critically ill patients transferred to ICU after abdominal surgery were identified. A nomogram prediction model for PPCs in critically ill surgical population was constructed using these factors, demonstrating a good predictive value.

Multi-omics analysis revealed the mechanism underlying flavonol biosynthesis during petal color formation in Camellia Nitidissima.

BACKGROUND: Camellia nitidissima is a rare, prized camellia species with golden-yellow flowers. It has a high ornamental, medicinal, and economic value. Previous studies have shown substantial flavonol accumulation in C. nitidissima petals during flower formation. However, the mechanisms underlying the golden flower formation in C. nitidissima remain largely unknown. RESULTS: We performed an integrative analysis of the transcriptome, proteome, and metabolome of the petals at five flower developmental stages to construct the regulatory network underlying golden flower formation in C. nitidissima. Metabolome analysis revealed the presence of 323 flavonoids, and two flavonols, quercetin glycosides and kaempferol glycosides, were highly accumulated in the golden petals. Transcriptome and proteome sequencing suggested that the flavonol biosynthesis-related genes and proteins upregulated and the anthocyanin and proanthocyanidin biosynthesis-related genes and proteins downregulated in the golden petal stage. Further investigation revealed the involvement of MYBs and bHLHs in flavonoid biosynthesis. Expression analysis showed that flavonol synthase 2 (CnFLS2) was highly expressed in the petals, and its expression positively correlated with flavonol content at all flower developmental stages. Transient overexpression of CnFLS2 in the petals increased flavonol content. Furthermore, correlation analysis showed that the jasmonate (JA) pathways positively correlated with flavonol biosynthesis, and exogenous methyl jasmonate (MeJA) treatment promoted CnFLS2 expression and flavonol accumulation. CONCLUSIONS: Our findings showed that the JA-CnFLS2 module regulates flavonol biosynthesis during golden petal formation in C. nitidissima.

[Diazotrophic abundance and community structure in rhizosphere soils of typical subtropical Cunninghamia lanceolata plantations]. / äºšçƒ­å¸¦å ¸åž‹æ‰æœ¨äººå·¥æž—æ ¹é™ åœŸå£¤å›ºæ°®èŒä¸°åº¦å’Œç¾¤è½ç»“æž„.

Rhizosphere is a vital area for substance exchange and energy transfer between roots and soil microorganisms. Therefore, diazotrophs in the rhizosphere play a pivotal role in facilitating plant nitrogen acquisition. We investigated the variability in the abundance and community structure of soil diazotrophs and the influencing factors across rhizosphere soils of Cunninghamia lanceolata in three locations: Baisha State-owned Forest Farm in Longyan City (BS), Sanming Forest Ecosystem and Global Change Research Station (SM), and Wuyishan National Forest Park in Nanping City (WYS), located in the western region of Fujian Province, quantified the diazotrophic abundance by using real-time quantitative PCR, and assessed the community structure by high-throughput sequencing. The results showed that soil pH, C:N ratio, and C:(N:P) stoichiometry in SM were notably lower compared to those in BS and WYS. In SM, the abundance of the nifH gene was 6.38×108 copies·g-1, significantly lower than 1.35×109 copies·g-1 in BS and 1.10×109 copies·g-1 in WYS. Additionally, α diversity index of diazotrophs was lower in SM compared to BS and WYS, while the community structure of diazotrophs in rhizosphere soils of BS and WYS was similar, which differed significantly from that in SM. The diazotrophic sequences in the three forest farms could be divided into 5 phylum, 8 classes, 15 orders, 23 families and 33 genera, with Proteobacteria, α-proteobacteria, and Bradyrhizobium as the dominant phylotypes. Soil pH, available phosphorus, NO3--N and C:(N:P) ratio were identified as significant factors influencing both the abundance and community structure of nifH genes, with soil pH performing the greatest. Taken together, there were spatial variations in the distribution of diazotrophic abundance and community structure in C. lanceolata rhizosphere soils, with soil pH as the primary driving factor.

Evaluating the impact of shift work on the risk of cardiometabolic disease: A Mendelian randomization study.

BACKGROUND AND AIMS: Evidence is increasingly suggesting that shift work is a risk factor for cardiometabolic disease. However, the causal relationship between shift work and cardiometabolic disease is not yet fully understood. In this study, we employed two-sample Mendelian randomization (MR) to investigate the causal relationship between shift work and the risk of cardiometabolic outcomes. METHODS AND RESULTS: Genome-wide association study (GWAS) statistics for shift work were obtained from the UK Biobank. Mendelian randomization analyses were conducted to explore the causal effects of shift work on cardiometabolic outcomes, using single-nucleotide polymorphisms (SNPs) as instrumental variables. The results suggested a causal effect between shift work and body mass index, body fat percentage, triglycerides, high-density lipoprotein, type 2 diabetes, hypertension, and cardiorespiratory fitness. After correcting for multiple tests, only body mass index and high-density lipoprotein showed significant associations. No causal effects were found between shift work and overweight, obesity, total cholesterol, low-density lipoprotein, fasting glucose, 2-h glucose, fasting insulin, coronary artery disease, myocardial infarction, heart failure, atrial fibrillation, or ischemic stroke. CONCLUSION: This MR study provides genetic evidence for a suggestive causal link between shift work and certain cardiometabolic outcomes. Our research may have the significance of providing insight into public hygiene to improve the understanding of shift work and cardiometabolic disease risk. Further experimental studies are needed to confirm our findings.

Identifying genetically-supported drug repurposing targets for non-small cell lung cancer through mendelian randomization of the druggable genome.

Background: Lung cancer is responsible for most cancer-related deaths, and non-small cell lung cancer (NSCLC) accounts for the majority of cases. Targeted therapy has made promising advancements in systemic treatment for NSCLC over the last two decades, but inadequate drug targets with clinically proven survival benefits limit its universal application in clinical practice compared to chemotherapy and immunotherapy. There is an urgent need to explore new drug targets to expand the beneficiary group. This study aims to identify druggable genes and to predict the efficacy and prognostic value of the corresponding targeted drugs in NSCLC. Methods: Two-sample mendelian randomization (MR) of druggable genes was performed to predict the efficacy of their corresponding targeted therapy for NSCLC. Subsequent sensitivity analyses were performed to assess potential confounders. Accessible RNA sequencing data were incorporated for subsequent verifications, and Kaplan-Meier survival curves of different gene expressions were used to explore the prognostic value of candidate druggable genes. Results: MR screening encompassing 4,863 expression quantitative trait loci (eQTL) and 1,072 protein quantitative trait loci (pQTL, with 453 proteins overlapping) were performed. Seven candidate druggable genes were identified, including CD33, ENG, ICOSLG and IL18R1 for lung adenocarcinoma, and VSIR, FSTL1 and TIMP2 for lung squamous cell carcinoma. The results were validated by further transcriptomic investigations. Conclusions: Drugs targeting genetically supported genomes are considerably more likely to yield promising efficacy and succeed in clinical trials. We provide compelling genetic evidence to prioritize drug development for NSCLC.

Andrographolide sensitizes glioma to temozolomide by inhibiting DKK1 expression.

BACKGROUND: Temozolomide (TMZ) is the first-line chemotherapeutic drug for gliomas treatment. However, the clinical efficacy of TMZ in glioma patients was very limited. Therefore, it is urgently needed to discover a novel approach to increase the sensitivity of glioma cells to TMZ. METHODS: Western blot, immunohistochemical staining, and qRT-PCR assays were used to explore the mechanisms underlying TMZ promoting DKK1 expression and andrographolide (AND) inhibiting DKK1 expression. HPLC was used to detect the ability of andrographolide (AND) to penetrate the blood-brain barrier. MTT assay, bioluminescence images, magnetic resonance imaging (MRI) and H&E staining were employed to measure the proliferative activity of glioma cells and the growth of intracranial tumors. RESULTS: TMZ can promote DKK1 expression in glioma cells and brain tumors of an orthotopic model of glioma. DKK1 could promote glioma cell proliferation and tumor growth in an orthotopic model of glioma. Mechanistically, TMZ increased EGFR expression and subsequently induced the activation of its downstream MEK-ERK and PI3K-Akt pathways, thereby promoting DKK1 expression in glioma cells. Andrographolide inhibited TMZ-induced DKK1 expression through inactivating MEK-ERK and PI3K-Akt pathways. Andrographolide can cross the blood-brain barrier, the combination of TMZ and andrographolide not only improved the anti-tumor effects of TMZ but also showed a survival benefit in an orthotopic model of glioma. CONCLUSION: Andrographolide can enhance anti-tumor activity of TMZ against glioma by inhibiting DKK1 expression.

Alendronate sodium induces G1 phase arrest and apoptosis in human umbilical vein endothelial cells by inhibiting ROS-mediated ERK1/2 signaling.

Bisphosphonates are potent bone resorption inhibitors, among which alendronate sodium (ALN) is commonly prescribed for most osteoporosis patients, but long-term application of ALN can cause bisphosphonate-related osteonecrosis of jaw (BRONJ), the pathogenesis of which remains unclear. Previous studies have suggested that bisphosphonates cause jaw ischemia by affecting the biological behavior of vascular endothelial cells, leading to BRONJ. However, the impacts of ALN on vascular endothelial cells and its mechanism remain unclear. The purpose of this work is to assess the influence of ALN on human umbilical vein endothelial cells (HUVECs) and clarify the molecular pathways involved. We found that high concentration of ALN induced G1 phase arrest in HUVECs, demonstrated by downregulation of Cyclin D1 and Cyclin D3. Moreover, high concentration of ALN treatment showed pro-apoptotic effect on HUVECs, demonstrated by increased levels of the cleaved caspase-3, the cleaved PARP and Bax, along with decreased levels of anti-apoptotic protein Bcl-2. Further experiments showed that ERK1/2 phosphorylation was decreased. Additionally, ALN provoked the build-up of reactive oxygen species (ROS) in HUVECs, leading to ERK1/2 pathway suppression. N-acetyl-L-cysteine (NAC), a ROS scavenger, efficiently promoted the ERK1/2 phosphorylation and mitigated the G1 phase arrest and apoptosis triggered by ALN in HUVECs. PD0325901, an inhibitor of ERK1/2 that diminishes the ERK1/2 phosphorylation enhanced the ALN-induced G1 phase arrest and apoptosis in HUVECs. These findings show that ALN induces G1 phase arrest and apoptosis through ROS-mediated ERK1/2 pathway inhibition in HUVECs, providing novel insights into the pathogenic process, prevention and treatment of BRONJ in individuals receiving extended use of ALN.

Distinct characteristics of social anxiety among youths with childhood sexual abuse: A latent profile analysis.

BACKGROUND: Childhood sexual abuse (CSA) is one type of childhood trauma that has long-term effects on physical and mental health, predisposing to social anxiety. OBJECTIVE: This study attempted to investigate the characteristics of different subgroups of social anxiety among youths with CSA experiences. PARTICIPANTS AND SETTING: 83,219 participants were recruited in a cross-sectional study from 63 colleges and universities in Jilin Province, China. METHODS: The main variables were measured by a series of self-report questionnaires. Latent profile analysis was used to classify different subgroups of social anxiety, and multiple logistic regression was employed to investigate factors influencing transitions between different subgroups. RESULTS: 3022 (3.63 %) youths who suffered from CSA (46.8 % were male, Mage = 19.57, SD = 1.76) could be divided into four subgroups of social anxiety: low-risk social anxiety (16.4 %), medium-risk social anxiety with high public speaking anxiety (30.3 %), medium-risk social anxiety with no prominent characteristics (22.9 %), and high-risk social anxiety (30.4 %). Shy bladder and bowel and virtual life orientation increased the level of social anxiety from low to medium and high risk. Smoking and drinking were more prevalent in the low- and medium-risk subgroups than in the high-risk subgroup. CONCLUSIONS: There was heterogeneity in different subgroups of social anxiety among youths with CSA experiences. Potential targeted prevention and intervention suggestions could be beneficial in mitigating the risk of social anxiety and further preventing the aggravation of risk between subgroups.

Intermittent fasting attenuates cognitive dysfunction and systemic disease activity in mice with neuropsychiatric systemic lupus erythematosus.

AIMS: Cognitive dysfunction and systemic disease activity are common manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE), a condition that affects a patient's health and quality of life. Clinical and preclinical studies have demonstrated that intermittent fasting (IF) improves health conditions and quality of life. Therefore, we aimed to test whether IF improves cognitive dysfunction and systemic disease activities in mice with NPSLE and to examine the underlying mechanisms. MAIN METHODS: NPSLE-prone MRL/lpr mice underwent 8 weeks of alternate-day fasting or ad libitum feeding, followed by behavioral tests to assess cognitive manifestations and biochemical tests to evaluate systemic disease activities. KEY FINDINGS: IF significantly improved cognitive functionality, decreased blood-brain barrier permeability, and reduced the activation of astrocytes and microglia in the hippocampi of MRL/lpr mice. IF also improved systemic disease activities, including reduced kidney glomerular injury and interstitial inflammation, peripheral blood autoantibody titer, and splenic T lymphocyte contents. Mechanistic studies demonstrated that IF attenuates cognitive dysfunction by facilitating the microglial transition to the M2-like phenotype via the AMPK/PPARγ/NF-κB pathway. SIGNIFICANCE: Together, observations from this study suggest a potential therapeutic benefit of IF in the treatment of cognitive dysfunction in patients with NPSLE.

Genetic evidence supporting potential causal roles of EIF4 family in breast cancer: a two-sample randomized Mendelian study.

Translational control plays a crucial role in the regulation of apoptosis, with the EIF4 family serving as one of the mRNA translation factors that modulate the process of mRNA translation based on mRNA characteristics. To address this potential causal role of EIF4 family proteins and breast cancer, Mendelian randomization was employed. The study incorporated four sets of genetics instrumental variables, namely EIF4E, EIF4B, EIF4A, and EIF4EBP2. The outcome variables selected for analysis were the BCAC consortium, which included estrogen receptor positive (ER+) and estrogen receptor negative (ER-) samples. To assess the potential violations of the MR assumption, the primary MR analysis employed inverse variance weighted (IVW), and several sensitivity analyses were conducted. The findings of the two-sample MR analysis indicate that EIF4E has an adverse effect on breast cancer risk (p = 0.028). However, the evidence for the relationship between EIF4E and ER status of breast cancer suggests a weak association with ER+ breast cancer (p = 0.054), but not with ER- breast cancer (p > 0.05). The study findings indicate that EIF4A is not causally linked to the risk of ER+ breast cancer, but is significantly associated with an elevated risk of ER- breast cancer (p = 0.028). However, the evidence is inadequate to support the effects of EIF4B and EIF4EBP2 on breast cancer (p > 0.05). Our results suggest that EIF4 may be a potential factor in the occurrence and development of breast cancer, which may lead to a better understanding of its causes and prevention.

Transcatheter Arterial Chemoembolization Combined with Hepatic Arterial Infusion Chemotherapy Versus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND/AIMS: In this study, we evaluated the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with hepatic arterial infusion chemotherapy (HAIC) compared to TACE monotherapy for the treatment of unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Relevant studies were systematically searched in PubMed, Embase, Web of Science, and Cochrane Library databases until September 1, 2023. Our analysis included 7 cohort studies encompassing a total of 630 patients. RESULTS: The results demonstrated that the TACE plus HAIC group exhibited significantly improved prognosis compared to the TACE alone group, as evidenced by superior rates of complete response, partial response, progressive disease, objective response rate, and disease control rate. Moreover, the TACE group displayed a lower risk of platelet reduction and vomiting when compared to the TACE plus HAIC group. None of the 7 studies reported any intervention-related mortality. CONCLUSION: In conclusion, the combination of TACE and HAIC may be recommended as a viable option for patients with unresectable HCC, given its evident enhancements in survival and tumor response rates without significant differences in adverse events when compared to TACE monotherapy. Nevertheless, additional randomized controlled trials and studies involving Western cohorts are warranted to further validate these findings.

Lithium Orbital Hybridization Chemistry to Stimulate Oxygen Redox with Reversible Phase Evolution in Sodium-Layered Oxide Cathodes.

Searching for high energy-density electrode materials for sodium ion batteries has revealed Na-deficient intercalation compounds with lattice oxygen redox as promising high-capacity cathodes. However, anionic redox reactions commonly encountered poor electrochemical reversibility and unfavorable structural transformations during dynamic (de)sodiation processes. To address this issue, we employed lithium orbital hybridization chemistry to create Na-O-Li configuration in a prototype P2-layered Na43/60Li1/20Mg7/60Cu1/6Mn2/3O2 (P2-NaLMCM') cathode material. That Li+ ions, having low electronegativity, reside in the transition metal slabs serves to stimulate unhybridized O 2p orbitals to facilitate the stable capacity contribution of oxygen redox at high state of charge. The prismatic-type structure evolving to an intergrowth structure of the Z phase at high charging state could be simultaneously alleviated by reducing the electrostatic repulsion of O-O layers. As a consequence, P2-NaLMCM' delivers a high specific capacity of 183.8 mAh g-1 at 0.05 C and good cycling stability with a capacity retention of 80.2% over 200 cycles within the voltage range of 2.0-4.5 V. Our findings provide new insights into both tailoring oxygen redox chemistry and stabilizing dynamic structural evolution for high-energy battery cathode materials.

The Hemagglutinin of Influenza A Virus Induces Ferroptosis to Facilitate Viral Replication.

Ferroptosis is a novel form of cell death caused by the accumulation of lipid peroxides in an iron-dependent manner. However, the precise mechanism underlying the exploitation of ferroptosis by influenza A viruses (IAV) remains unclear. The results demonstrate that IAV promotes its own replication through ferritinophagy by sensitizing cells to ferroptosis, with hemagglutinin identified as a key trigger in this process. Hemagglutinin interacts with autophagic receptors nuclear receptor coactivator 4 (NCOA4) and tax1-binding protein 1 (TAX1BP1), facilitating the formation of ferritin-NCOA4 condensates and inducing ferritinophagy. Further investigation shows that hemagglutinin-induced ferritinophagy causes cellular lipid peroxidation, inhibits aggregation of mitochondrial antiviral signaling protein (MAVS), and suppresses the type I interferon response, thereby contributing to viral replication. Collectively, a novel mechanism by which IAV hemagglutinin induces ferritinophagy resulting in cellular lipid peroxidation, consequently impairing MAVS-mediated antiviral immunity, is revealed.