Safety and effectiveness of left atrial appendage closure in atrial fibrillation patients with different types of heart failure.

BACKGROUND: Both atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases. If the two exist together, the risk of stroke, hospitalization for HF and all-cause death is increased. Currently, research on left atrial appendage closure (LAAC) in patients with AF and HF is limited and controversial. This study was designed to investigate the safety and effectiveness of LAAC in AF patients with different types of HF. METHODS: Patients with non-valvular atrial fibrillation (NVAF) and HF who underwent LAAC in the First Affiliated Hospital of Army Medical University from August 2014 to July 2021 were enrolled. According to left ventricular ejection fraction (LVEF), the study divided into HF with reduced ejection fraction (LVEF < 50%, HFrEF) group and HF with preserved ejection fraction (LVEF ≥ 50%, HFpEF) group. The data we collected from patients included: gender, age, comorbid diseases, CHA2DS2-VASc score, HAS-BLED score, NT-proBNP level, residual shunt, cardiac catheterization results, occluder size, postoperative medication regimen, transthoracic echocardiography (TTE) results and transesophageal echocardiography (TEE) results, etc. Patients were followed up for stroke, bleeding, device related thrombus (DRT), pericardial tamponade, hospitalization for HF, and all-cause death within 2 years after surgery. Statistical methods were used to compare the differences in clinical outcome of LAAC in AF patients with different types of HF. RESULTS: Overall, 288 NVAF patients with HF were enrolled in this study, including 142 males and 146 females. There were 74 patients in the HFrEF group and 214 patients in the HFpEF group. All patients successfully underwent LAAC. The CHA2DS2-VASc score and HAS-BLED score of HFrEF group were lower than those of HFpEF group. A total of 288 LAAC devices were implanted. The average diameter of the occluders was 27.2 ± 3.5 mm in the HFrEF group and 26.8 ± 3.3 mm in the HFpEF group, and there was no statistical difference between the two groups (P = 0.470). Also, there was no statistically significant difference in the occurrence of residual shunts between the two groups as detected by TEE after surgery (P = 0.341). LVEF was significantly higher in HFrEF group at 3 days, 3 months and 1 year after operation than before (P < 0.001). At 45-60 days after surgery, we found DRT in 9 patients and there were 4 patients (5.4%) in HFrEF group and 5 patients (2.3%) in HFpEF group, with no significant difference between the two groups (P = 0.357). One patient with DRT had stroke. The incidence of stroke was 11.1% in patients with DRT and 0.7% in patients without DRT (P = 0.670). There was one case of postoperative pericardial tamponade, which was improved by pericardiocentesis at 24 h after surgery in the HFpEF group, and there was no significant difference between the two groups (P = 1.000). During a mean follow-up period of 49.7 ± 22.4 months, there were no significant differences in the incidence of stroke, bleeding, DRT and HF exacerbation between the two groups. We found a statistical difference in the improvement of HF between HFrEF group and HFpEF group (P < 0.05). CONCLUSIONS: LAAC is safe and effective in AF patients with different types of HF. The improvement of cardiac function after LAAC is more pronounced in HFrEF group than in HFpEF group.

Symptom experience and self-management strategies of adults undergoing hematopoietic stem cell transplantation after hospital discharge: A longitudinal qualitative study.

PURPOSE: To explore the symptom experience and self-management strategies of adults undergoing hematopoietic stem cell transplantation after hospital discharge. METHODS: A longitudinal qualitative study was employed. A heterogeneous sample of 22 patients who underwent hematopoietic stem cell transplantation from August 2022 to April 2023 were included. Semi-structured interviews were conducted at three time points post-discharge and provided a dataset of 56 interviews. The content analysis method was used for manual analysis. This study followed the COREQ checklist. RESULTS: The data from this study were categorized into four themes and 14 subthemes: (1) complexity and multidimensionality of symptom experience: diversity, dynamism, continuity, relatedness, and functional loading; (2) multiple variations in symptom self-management; (3) barriers to symptom self-management: limited access to information resources, insufficient awareness and skills in symptom self-management, lack of economic and social support, and difficulties in medical visits and reviews; and (4) facilitators of symptom self-management: perceived benefits, experience-driven, and peer experiences. CONCLUSION: Patients undergoing hematopoietic stem cell transplantation experience multiple and complex symptom experiences after hospital discharge, and their symptom self-management remains challenging. The findings underscore the necessity for healthcare professionals to regularly and consistently evaluate the symptoms and self-management practices of patients undergoing hematopoietic stem cell transplantation and execute focused interventions to alleviate their symptom load and enhance their long-term well-being.

The Protective Role of Quercetin Against Copper-Induced Female Reproductive Toxicity: Insights from Transcriptome Analysis.

Quercetin has been shown to mitigate the cytotoxic effects of heavy metals. While copper is an essential trace element for bodily functions, excessive intake has been linked to impaired female reproductive function. Transcriptome analysis was employed to identify genes that are differentially expressed in response to high copper and were validated through qRT-PCR and WB. ATP content and Tunel were used to identify the damage of mitochondrial and cell apoptosis. PPI analysis revealed that MKI67, TOPII, ASPM, CASP3, PLK1, and TTK are central proteins within the network. Additionally, exposure to elevated levels of copper resulted in the dysregulation of 86 genes associated with mitochondria. Conversely, treatment with quercetin (QUE) in combination with high copper led to the normalization of 42 mitochondria-related genes previously affected by high copper levels. Furthermore, CuSO4 decreases ATP content and induces cell apoptosis, which can be reversed by QUE. Results suggest that elevated copper levels can lead to oxidative stress and apoptosis by inducing mitochondrial damage, while QUE has the potential to mitigate these effects, ultimately safeguarding granulosa cells and halting the progression of cell death. This study provides novel insights into the molecular pathways involved in female reproductive toxicity caused by excessive copper exposure.

Exploring the mechanism of Pueraria lobata (Willd.) Ohwi in the regulation of obesity.

ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria lobata (Willd.) Ohwi is a traditional medicinal and edible homologous plant rich in flavonoids, triterpenes, saponins, polysaccharides and other chemical components. At present, studies have shown that PR has the effect of lowering blood sugar, improving insulin sensitivity and inhibiting obesity. However, the specific mechanism of PR inhibits obesity is still unclear, and there are few researches on the anti-obesity effect of PR through the combination of network pharmacology and experiment. AIM OF THE STUDY: Pharmacology, molecular docking technology and experimental verification through the network, revealing the Pueraria lobata radix (PR) the material basis of obesity and the potential mechanism. METHODS AND RESULTS: The present study used network pharmacology techniques to investigate the therapeutic effect and mechanism of action of PR. Through relevant databases, a total of 6 main chemical components and 257 potential targets were screened. Protein interaction analysis shows that AKT1, AKR1B1, PPARG, MMP9, TNF, TP53, BAD, and BCL2 are core targets. Enrichment analysis shows that the pathway of PR in preventing obesity involves the cancer signaling pathway and the PI3K-Akt signaling pathway, which may be the main pathways of action. Further molecular docking verification indicates that its core target exhibits good binding activity with 4 compounds: formononectin, purerin, 7,8,4 '- trihydroxide and daidzein. Using the ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) technology to detected and confirmed these main compounds. Cell experiment results revealed that puerarin inhibits cell proliferation and differentiation in a concentration dependent manner, significantly promoting cell apoptosis and affecting cell migration. Animal experiments have shown that puerarin reduces food intake and weight gain in mice. It was found that puerarin can upregulate HDL and downregulate TC, TG, and LDL blood biochemical indicators. Western blot results showed that puerarin significantly inhibited the expression of AKT1, AKR1B1, MMP9, TNF, TP53, BCL2, PPARG, and significantly increased the expression of BAD protein at both cellular and animal levels. CONCLUSION: The present study established a method for measuring PR content and predicted its active ingredients and their mechanisms of action in the treatment of obesity, providing a theoretical basis for further research.

A novel homozygous nonsense variant of STX2 underlies non-obstructive azoospermia in a consanguineous Chinese family.

Male infertility is a widespread population health concern, causing various degrees of adverse fertility outcomes. We determined the genetic cause of an infertile male from a consanguineous family, expanding the mutant spectrum of male infertility. A non-obstructive azoospermia (NOA) patient was recruited, and histological type of human testicular tissue of the patient categorized as maturation arrest. We identified a novel loss-of-function variant of syntaxin 2 (STX2) (c.142C>T:p.Gln48*) by performing Whole-exome sequencing (WES) on the NOA patient from a consanguineous Chinese family. Sanger sequencing confirmed the p.Gln48* variant was maternally and paternally inherited. The variant was predicted to be deleterious and resulted in aberrant changes to structure and function of STX2 by In silico analysis. In summary, we reported for the first time that a nonsense variant occurred in the exon region of STX2 in an infertile male presenting with NOA, which was beneficial for diagnosis and therapies of NOA.

Increased viral tolerance mediates by antiviral RNA interference in bat cells.

Bats harbor highly virulent viruses that can infect other mammals, including humans, posing questions about their immune tolerance mechanisms. Bat cells employ multiple strategies to limit virus replication and virus-induced immunopathology, but the coexistence of bats and fatal viruses remains poorly understood. Here, we investigate the antiviral RNA interference pathway in bat cells and discover that they have an enhanced antiviral RNAi response, producing canonical viral small interfering RNAs upon Sindbis virus infection that are missing in human cells. Disruption of Dicer function results in increased viral load for three different RNA viruses in bat cells, indicating an interferon-independent antiviral pathway. Furthermore, our findings reveal the simultaneous engagement of Dicer and pattern-recognition receptors, such as retinoic acid-inducible gene I, with double-stranded RNA, suggesting that Dicer attenuates the interferon response initiation in bat cells. These insights advance our comprehension of the distinctive strategies bats employ to coexist with viruses.

Transcriptome Analysis Reveals the Role of Sucrose in the Production of Latilactobacillus sakei L3 Exopolysaccharide.

Latilactobacillus (L.) sakei is a species of lactic acid bacteria (LAB) mostly studied according to its application in food fermentation. Previously, L. sakei L3 was isolated by our laboratory and possessed the capability of high exopolysaccharide (EPS) yield during sucrose-added fermentation. However, the understanding of sucrose promoting EPS production is still limited. Here, we analyzed the growth characteristics of L. sakei L3 and alterations of its transcriptional profiles during sucrose-added fermentation. The results showed that L. sakei L3 could survive between pH 4.0 and pH 9.0, tolerant to NaCl (<10%, w/v) and urea (<6%, w/v). Meanwhile, transcriptomic analysis showed that a total of 426 differentially expressed genes and eight non-coding RNAs were identified. Genes associated with sucrose metabolism were significantly induced, so L. sakei L3 increased the utilization of sucrose to produce EPS, while genes related to uridine monophosphate (UMP), fatty acids and folate synthetic pathways were significantly inhibited, indicating that L. sakei L3 decreased self-growth, substance and energy metabolism to satisfy EPS production. Overall, transcriptome analysis provided valuable insights into the mechanisms by which L. sakei L3 utilizes sucrose for EPS biosynthesis. The study provided a theoretical foundation for the further application of functional EPS in the food industry.

Synergism in Binary Nanocrystals Enables Top-Illuminated HgTe Colloidal Quantum Dot Short-Wave Infrared Imager.

Thanks to their tunable infrared absorption, solution processability, and low fabrication costs, HgTe colloidal quantum dots (CQDs) are promising for optoelectronic devices. Despite advancements in device design, their potential for imaging applications remains underexplored. For integration with Si-based readout integrated circuits (ROICs), top illumination is necessary for simultaneous light absorption and signal acquisition. However, most high-performing traditional HgTe CQD photodiodes are p-on-n stack and bottom-illuminated. Herein, we report top-illuminated inverted n-on-p HgTe CQD photodiodes using a robust p-type CQD layer and a thermally evaporated Bi2S3 electron transport layer. The p-type CQD solid is achieved by exploring the synergism in binary HgTe and Ag2Te CQDs. These photodetectors show a room-temperature detectivity of 3.4 × 1011 jones and an EQE of ∼44% at ∼1.7 µm wavelength, comparable to the p-on-n HgTe CQD photodiodes. A top-illuminated HgTe CQD short-wave infrared imager (640 × 512 pixels) was fabricated, demonstrating successful infrared imaging.

Association between Elastic Modulus of Foot Soft Tissues and Gait Characteristics in Young Individuals with Flatfoot.

Flatfoot is a common foot deformity, causing foot pain, osteoarthritis of the midfoot, and even knee and hip dysfunction. The elastic modulus of foot soft tissues and its association with gait biomechanics still remain unclear. For this study, we recruited 20 young individuals with flatfoot and 22 age-matched individuals with normal foot arches. The elastic modulus of foot soft tissues (posterior tibial tendon, flexor digitorum brevis, plantar fascia, heel fat pad) was obtained via ultrasound elastography. Gait data were acquired using an optical motion capture system. The association between elastic modulus and gait data was analyzed via correlation analysis. The elastic modulus of the plantar fascia (PF) in individuals with flatfoot was higher than that in individuals with normal foot arches. There was no significant difference in the elastic modulus of the posterior tibial tendon (PTT), the flexor digitorum brevis (FDB), or the heel fat pad (HFD), or the thickness of the PF, PTT, FDB, and HFD. Individuals with flatfoot showed greater motion of the hip and pelvis in the coronal plane, longer double-support phase time, and greater maximum hip adduction moment during walking. The elastic modulus of the PF in individuals with flatfoot was positively correlated with the maximum hip extension angle (r = 0.352, p = 0.033) and the maximum hip adduction moment (r = 0.429, p = 0.039). The plantar fascia is an important plantar structure in flatfoot. The alteration of the plantar fascia's elastic modulus is likely a significant contributing factor to gait abnormalities in people with flatfoot. More attention should be given to the plantar fascia in the young population with flatfoot.

Integration of transcriptome and machine learning to identify the potential key genes and regulatory networks affecting drip loss in pork.

Low level of drip loss (DL) is an important quality characteristic of meat with high economic value. However, the key genes and regulatory networks contributing to DL in pork remain largely unknown. To accurately identify the key genes affecting DL in muscles postmortem, 12 Duroc × (Landrace × Yorkshire) pigs with extremely high (n = 6, H group) and low (n = 6, L group) DL at both 24 and 48 h postmortem were selected for transcriptome sequencing. The analysis of differentially expressed genes and weighted gene co-expression network analysis (WGCNA) were performed to find the overlapping genes using the transcriptome data, and functional enrichment and protein-protein interaction (PPI) network analysis were conducted using the overlapping genes. Moreover, we used machine learning to identify the key genes and regulatory networks related to DL based on the interactive genes of the PPI network. Finally, nine potential key genes (IRS1, ESR1, HSPA6, INSR, SPOP, MSTN, LGALS4, MYLK2, and FRMD4B) mainly associated with the MAPK signaling pathway, the insulin signaling pathway, and the calcium signaling pathway were identified, and a single-gene set enrichment analysis (GSEA) was performed to further annotate the functions of these potential key genes. The GSEA results showed that these genes are mainly related to ubiquitin-mediated proteolysis and oxidative reactions. Taken together, our results indicate that the potential key genes influencing DL are mainly related to insulin signaling mediated differences in glycolysis and ubiquitin-mediated changes in muscle structure and improve the understanding of gene expression and regulation related to DL and contribute to future molecular breeding for improving pork quality.

A low level of drip loss (DL) is critical for the economic value of pork. However, the genetic basis underlying DL remains unclear. In this study, pigs with extremely high and low DL at both 24 and 48 h postmortem were selected, and total RNA from longissimus dorsi (LD) muscles was extracted for transcriptome sequencing. Subsequently, a variety of analytical methods, were integrated to identify the potential key genes and pathways affecting DL. As a result, nine potential key genes (IRS1, ESR1, HSPA6, INSR, SPOP, MSTN, LGALS4, MYLK2, and FRMD4B) mainly associated with the MAPK signaling pathway, insulin signaling pathway, and calcium signaling pathway, were identified, and these genes are primarily related to ubiquitin-mediated proteolysis and oxidation reactions. This study contributes new evidence for elucidating the molecular mechanism of DL and provides potential target genes for precise genetic improvement of DL.

Decoupling the correlation between cytotoxic and exhausted T lymphocyte states enhances melanoma immunotherapy response prediction.

Cytotoxic T lymphocyte (CTL) and terminal exhausted T lymphocyte (ETL) activities crucially influence immune checkpoint inhibitor (ICI) response. Despite this, the efficacy of ETL and CTL transcriptomic signatures for response prediction remains limited. Investigating this across the TCGA and publicly available single-cell cohorts, we find a strong positive correlation between ETL and CTL expression signatures in most cancers. We hence posited that their limited predictability arises due to their mutually canceling effects on ICI response. Thus, we developed DETACH, a computational method to identify a gene set whose expression pinpoints to a subset of melanoma patients where the CTL and ETL correlation is low. DETACH enhances CTL's prediction accuracy, outperforming existing signatures. DETACH signature genes activity also demonstrates a positive correlation with lymphocyte infiltration and the prevalence of reactive T cells in the tumor microenvironment (TME), advancing our understanding of the CTL cell state within the TME.

Color-Tunable Room-Temperature Phosphorescence from Non-Aromatic-Polymer-Involved Charge Transfer.

Polymeric room-temperature phosphorescence (RTP) materials especially multicolor RTP systems hold great promise in concrete applications. A key feature in these applications is a triplet charge transfer transition. Aromatic electron donors and electron acceptors are often essential to ensure persistent RTP. There is much interest in fabricating non-aromatic charge-transfer-mediated RTP materials and it still remains a formidable challenge to achieve color-tunable RTP via charge transfer. Herein, a charge-transfer-mediated RTP material by embedding quinoline derivatives within a non-aromatic polymer matrix such as polyacrylamide (PAM) or polyvinyl alcohol (PVA) is developed. Through-space charge transfer (TSCT) is achieved upon alkali- or heat treatment to realize a long phosphorescence lifetime of up to 629.90 ms, high phosphorescence quantum yield of up to 20.51%, and a green-to-blue afterglow for more than 20 s at room temperature. This color-tunable RTP emerges from a nonaromatic polymer to single phosphor charge transfer that has rarely been reported before. This finding suggests that an effective and simple approach can deliver new color-tunable RTP materials for applications including multicolor display, information encryption, and gas detection.

Selective Oxidation of Alcohol to Valuable Aldehydes Using Water as a Promoter in a Photoelectrochemical Cell.

Artificial photoelectrochemistry (PEC) has emerged as a promising and efficient technology for the sustainable conversion of solar energy into chemicals. In this study, we present a refined PEC process that enables the highly selective and stable production of piperonal and other valuable aldehydes through the oxidation of the corresponding alcohols. By employing Fe2O3 or TiO2 as the photoanode material and 2,2,6,6-tetramethylpiperidinooxy (TEMPO) as a redox mediator in an H2O/acetonitrile solution, we achieve 100% selectivity and a >95% Faradaic efficiency for piperonal production from piperonyl alcohol (PA) oxidation. Remarkably, we reveal the enhancing effect on the PA oxidation reactivity of appropriate-amount water in the solvent as it plays a crucial role in inhibiting the photoelectron-hole recombination efficiency and facilitating charge transfer. Mechanistic analysis suggests that TEMPO-mediated PA oxidation involves the formation of •O2- radicals by the reduction of oxygen on the cathode, resulting in water as the sole byproduct. Furthermore, our PEC oxidation system exhibits applications on the 100%-selective production of various conjugated aldehydes, including 4-anisaldehyde, cuminaldehyde, and the vitamin B6 derivative. By implementing a TiO2//Fe2O3 dual-photoanode system, we achieve an enhanced piperonal production rate of 31.2 µmol h-1 cm-2 at 1.0 V vs Ag/Ag+ and demonstrate its stability over a 102 h cyclic test, ensuring near-quantitative yield. This research illuminates the potential of the PEC strategy as a generally applicable method for the efficient production of high-value aldehydes.

Understanding the dynamics of microplastics transport in urban stormwater runoff: Implications for pollution control and management.

The transport of microplastics (MPs) from urban environments to water resources via stormwater runoff poses significant concerns due to its adverse impacts on water safety and aquatic ecosystems. This study presents a modeling approach aimed at understanding the transport mechanisms of MPs in an urban residential setting, considering settling and buoyant MPs. To consider the effect of MP shapes, the settling velocity of various settling MPs in shapes of fibers, films, and fragments was calculated. Using an analogy of sediment transport, a Rouse number criterion was used to analyze the transport of MPs. For buoyant MPs, it was assumed that they transport as wash-load as soon as they float in the water and the travel time for them to reach the storm drain was determined. The calculation of settling velocity revealed the influence of shape on the settling velocity of MPs was particularly pronounced as the equivalent diameter of the MPs increased. The transport mechanism for the smallest settling MPs, irrespective of their shapes, density, and depth of flow, was wash-load. However, for larger MPs, the shape and size distribution of settling MPs, along with the depth of flow and slope significantly influenced their transport mechanisms compared to sediment particles. The influence of weathering on the MPs' transport mechanisms depended on their sizes and shapes. The site-specific characteristics, including slope and surface friction, significantly influenced the velocity of stormwater runoff and, consequently, the extent of MP transport during rain events. Moreover, an evaluation of the transport mechanism of settling MPs was conducted using the reported field data on MP abundance in road dust collected from residential and traffic sites. This study underscores the complexity of MP transport dynamics and provides a foundation for developing targeted strategies to mitigate MP pollution in urban environments.

Identification of a Homozygous Mutation of CCDC40 in a Chinese Infertile Man with MMAF and PCD-like Phenotypes.

Aims: Asthenozoospermia is the most common factor of male infertility, mainly caused by multiple morphological abnormalities of the sperm flagella (MMAF) and primary ciliary dyskinesia (PCD). Previous studies have shown that genetic factors may contribute to MMAF and PCD. The study aimed to identify novel potentially pathogenic gene mutations in a Chinese infertile man with MMAF and PCD-like phenotypes. Methods: A Chinese infertile man with MMAF and PCD was enrolled in this study. Whole exome sequencing and Sanger sequencing were performed to identify potential causative genes and mutations. Results: A novel homozygous missense mutation (c.1450G>A; p.E484K) of CCDC40 was finally identified and Sanger sequencing confirmed that the patient carried the homozygous mutation, which was inherited from his parents. We reported the first homozygous missense CCDC40 mutation in infertile men with MMAF but had other milder PCD symptoms. Conclusion: Our findings not only broaden the disease-causing mutation spectrum of CCDC40 but also provide new insight into the correlation between CCDC40 mutations and MMAF.

Rapid Glutathione Analysis with SERS Microneedles for Deep Glioblastoma Tissue Differentiation.

Rapid tissue differentiation at the molecular level is a prerequisite for precise surgical resection, which is of special value for the treatment of malignant tumors, such as glioblastoma (GBM). Herein, a SERS-active microneedle is prepared by modifying glutathione (GSH)-responsive molecules, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), on the surface of Au@Ag substrates for the distinction of different GBM tissues. Since the Raman signals on the surface of the DTNB@Au@Ag microneedle can be collected by both portable and benchtop Raman spectrometers, the distribution of GSH in different tissues at centimeter scale can be displayed through Raman spectroscopy and Raman imaging, and the entire analysis process can be accomplished within 12 min. Accordingly, in vivo brain tissues of orthotopic GBM xenograft mice and ex vivo tissues of GBM patients are accurately differentiated with the microneedle, and the results are well consistent with tissue staining and postoperative pathological reports. In addition, the outline of tumor, peritumoral, and normal tissues can be indicated by the DTNB@Au@Ag microneedle for at least 56 days. Considering that the tumor tissues are quickly discriminated at the molecular level without the restriction of depth, the DTNB@Au@Ag microneedle is promising to be a powerful intraoperative diagnostic tool for surgery navigation.

GPR55 activation improves anxiety- and depression-like behaviors of mice during methamphetamine withdrawal.

Methamphetamine is a potent and highly addictive neurotoxic psychostimulant that triggers a spectrum of adverse emotional responses during withdrawal. G-protein coupled receptor 55 (GPR55), a novel endocannabinoid receptor, is closely associated with mood regulation. Herein, we developed a murine model of methamphetamine-induced anxiety- and depressive-like behavior during abstinence which showed a decreased GPR55 expression in the hippocampus. Activation of GPR55 mitigated these behavioral symptoms, concomitantly ameliorating impairments in hippocampal neurogenesis and reducing neuroinflammation. These findings underscore the pivotal role of GPR55 in mediating the neuropsychological consequences of methamphetamine withdrawal, potentially via mechanisms involving the modulation of hippocampal neurogenesis and inflammation.

How COVID-19 Information Fear of Missing out Increases the Risk of Depression and Anxiety: Roles of Resilience and Personality Types.

During major health emergencies (e.g., the COVID-19 pandemic) people often fear missing relevant information. COVID-19 information fear of missing out (FOMO) is a phenomenon where people feel anxiety about losing control of COVID-19-related information. The present study aimed to examine how COVID-19 information FOMO relates to mental health (e.g., depression and anxiety), the mediating role of resilience, and the moderating role of personality types during the COVID-19 pandemic. We surveyed 1442 Chinese undergraduates (Mage = 21.68 ± 2.35 years) on the relevant variables. The results showed that COVID-19 information FOMO was positively associated with depression and anxiety, and resilience mediated these associations. Latent profile analysis (LPA) identified three personality types (undercontrolled, adaptive, and overcontrolled). Personality types moderated the mediation models, in which the indirect effects were only significant in the participants classified in the undercontrolled group rather than the participants classified in the other two groups. This study told us that undergraduates' mental health, particularly that of the undercontrollers, should be paid attention to when responding to a major public health emergency (e.g., the COVID-19 pandemic).

New genetic insights into immunotherapy outcomes in gastric cancer via single-cell RNA sequencing and random forest model.

OBJECTIVE: The high mortality rate of gastric cancer, traditionally managed through surgery, underscores the urgent need for advanced therapeutic strategies. Despite advancements in treatment modalities, outcomes remain suboptimal, necessitating the identification of novel biomarkers to predict sensitivity to immunotherapy. This study focuses on utilizing single-cell sequencing for gene identification and developing a random forest model to predict immunotherapy sensitivity in gastric cancer patients. METHODS: Differentially expressed genes were identified using single-cell RNA sequencing (scRNA-seq) and gene set enrichment analysis (GESA). A random forest model was constructed based on these genes, and its effectiveness was validated through prognostic analysis. Further, analyses of immune cell infiltration, immune checkpoints, and the random forest model provided deeper insights. RESULTS: High METTL1 expression was found to correlate with improved survival rates in gastric cancer patients (P = 0.042), and the random forest model, based on METTL1 and associated prognostic genes, achieved a significant predictive performance (AUC = 0.863). It showed associations with various immune cell types and negative correlations with CTLA4 and PDCD1 immune checkpoints. Experiments in vitro and in vivo demonstrated that METTL1 enhances gastric cancer cell activity by suppressing T cell proliferation and upregulating CTLA4 and PDCD1. CONCLUSION: The random forest model, based on scRNA-seq, shows high predictive value for survival and immunotherapy sensitivity in gastric cancer patients. This study underscores the potential of METTL1 as a biomarker in enhancing the efficacy of gastric cancer immunotherapy.

Effects of low protein feed on hepato-intestinal health and muscle quality of grass carp (Ctenopharyngodon idellus).

In this study, grass carp (33.28 ± 0.05 g) were fed three diets for 8 weeks: control (crude protein [CP] 30%, crude lipid [CL] 6%), low protein (LP; CP16%, CL6%), and low protein with high-fat (LPHF; CP16%, CL10%). The final body weight decreased in the LP and LPHF groups compared to the Control (P < 0.05). Liver triglycerides, total cholesterol, and nonesterified fatty acids were higher in the LP group than the Control, whereas these indexes in the LPHF group were higher than those in the LP group (P < 0.05). The LP group had intestinal barrier damage, while the LPHF group had a slight recovery. TNF-α, IL-8, and IL-1ß content were lower in the LP group than in the Control (P < 0.05), and even higher in the LPHF group (P < 0.05). The expressions of endoplasmic reticulum stress-related genes Activating transcription factor 6 (ATF-6) and Glucose-regulated protein (GRP78) were higher in the LPHF group against the LP group (P < 0.05). The IL-1ß and TNF-α content negatively correlated with intestinal Actinomycetes and Mycobacterium abundance (P < 0.05). The muscle fiber diameter was smaller in both the LP and LPHF groups than the control (P < 0.05), with the LP group showing metabolites related to protein digestion and absorption, and LPHF group exhibiting metabolites related to taste transmission. The results demonstrate reducing dietary protein affects growth, causing liver lipid accumulation, reduced enteritis response, and increased muscle tightness, while increasing fat content accelerates fat accumulation and inflammation.