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Abstract The tumor microenvironment (TME) is pivotal in non-small cell lung cancer (NSCLC) progression, influencing drug resistance and immune cell behavior through complex ligand-receptor (LR) interactions. This study developed an epithelial LR-related prognostic risk score (LRrisk) to identify biomarkers and targets in NSCLC. We identified twenty epithelial LRs with significant prognostic implications and delineated three molecular NSCLC subtypes with distinct outcomes, pathological characteristics, biological pathways, and immune profiles. The LRrisk model was constructed using twelve differentially expressed ligand-receptor interaction-related genes (LRGs), with a focus on POPDC3 (popeye domain-containing protein 3), which was overexpressed in NSCLC cells. Functional assays revealed that POPDC3 knockdown reduced cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while its overexpression promoted cancerous activities. In vivo, POPDC3 silencing hindered, and its overexpression accelerated the growth of NSCLC xenografts in nude mice. Additionally, high expression levels of POPDC3 in NSCLC tissues were associated with enhanced CD4+ T cell infiltration and increased PD-1 expression within the TME. Moreover, ectopic POPDC3 overexpression in C57BL/6 J mouse Lewis lung carcinoma (LLC) xenografts enhanced CD4+ T cell infiltration and PD-1 expression in the TME. This research establishes a robust epithelial LR-related signature, highlighting POPDC3 as a critical facilitator of NSCLC progression and a potential therapeutic target.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19) pandemic and is continuously spreading globally. The continuous emergence of new SARS-CoV-2 variants keeps posing threats, highlighting the need for fast-acting, mutation-resistant broad-spectrum therapeutics. Protein translation is vital for SARS-CoV-2 replication, producing early non-structural proteins for RNA replication and transcription, and late structural proteins for virion assembly. Targeted blocking of viral protein translation is thus a potential approach to developing effective anti-SARS-CoV-2 drugs. SARS-CoV-2, as an obligate parasite, utilizes the host’s translation machinery. Translation-blocking strategies that target the SARS-CoV-2 mRNA, especially those that target its conserved elements are generally preferred. In this review, we discuss the current understanding of SARS-CoV-2 translation, highlighting the important conserved motifs and structures involved in its regulation. We also discuss the current strategies for blocking SARS-CoV-2 translation through viral RNA degradation or RNA element dysfunction.

Abstract The reconstruction of damaged neural circuits is critical for neurological repair after brain injury. Classical brain-computer interfaces (BCIs) allow direct communication between the brain and external controllers to compensate for lost functions. Importantly, there is increasing potential for generalized BCIs to input information into the brains to restore damage, but their effectiveness is limited when a large injured cavity is caused. Notably, it might be overcome by transplantation of brain organoids into the damaged region. Here, we construct innovative BCIs mediated by implantable organoids, coined as organoid-brain-computer interfaces (OBCIs). We assess the prolonged safety and feasibility of the OBCIs, and explore neuroregulatory strategies. OBCI stimulation promotes progressive differentiation of grafts and enhances structural-functional connections within organoids and the host brain, promising to repair the damaged brain via regenerating and regulating, potentially directing neurons to preselected targets and recovering functional neural networks in the future.

Abstract Integrated biochemical and biophysical signals regulate embryonic development. Correct neural tube formation is critical for the development of central nervous system. However, the role of microgravity in neurodevelopment and its underlying molecular mechanisms remain unclear. In this study, the effects of stimulated microgravity (SMG) on the development of human brain organoids are investigated. SMG impairs N‐cadherin‐based adherens junction formation, leading to neural tube defects associated with dysregulated self‐renewal capacity and neuroepithelial disorganization in human brain organoids. Bulk gene expression analyses reveal that SMG alters Hippo and BMP signaling in brain organoids. The neuropathological deficits in SMG‐treated organoids can be rescued by regulating YAP/BMP/ID1 axis. Furthermore, sing‐cell RNA sequencing data show that SMG results in perturbations in the number and function of neural stem and progenitor cell subpopulations. One of these subpopulations senses SMG cues and transmits BMP signals to the subpopulation responsible for tube morphogenesis, ultimately affecting the proliferating cell population. Finally, SMG intervention leads to persistent neurologic damage even after returning to normal gravity conditions. Collectively, this study reveals molecular and cellular abnormalities associated with SMG during human brain development, providing opportunities for countermeasures to maintain normal neurodevelopment in space.

The reconstruction of neural function and recovery of chronic damage following traumatic brain injury (TBI) remain significant clinical challenges. Exosomes derived from neural stem cells (NSCs) offer various benefits in TBI treatment. Numerous studies confirmed that appropriate preconditioning methods enhanced the targeted efficacy of exosome therapy. Interferon-gamma (IFN-γ) possesses immunomodulatory capabilities and is widely involved in neurological disorders. In this study, IFN-γ was employed for preconditioning NSCs to enhance the efficacy of exosome (IFN-Exo, IE) for TBI. miRNA sequencing revealed the potential of IFN-Exo in promoting neural differentiation and modulating inflammatory responses. Through low-temperature 3D printing, IFN-Exo was combined with collagen/chitosan (3D-CC-IE) to preserve the biological activity of the exosome. The delivery of exosomes via biomaterial scaffolds benefited the retention and therapeutic potential of exosomes, ensuring that they could exert long-term effects at the injury site. The 3D-CC-IE scaffold exhibited excellent biocompatibility and mechanical properties. Subsequently, 3D-CC-IE scaffold significantly improved impaired motor and cognitive functions after TBI in rat. Histological results showed that 3D-CC-IE scaffold markedly facilitated the reconstruction of damaged neural tissue and promoted endogenous neurogenesis. Further mechanistic validation suggested that IFN-Exo alleviated neuroinflammation by modulating the MAPK/mTOR signaling pathway. In summary, the results of this study indicated that 3D-CC-IE scaffold engaged in long-term pathophysiological processes, fostering neural function recovery after TBI, offering a promising regenerative therapy avenue.

Abstract Aim To examine the prognostic value of superoxide dismutase (SOD) activity for monitoring reduced left ventricular ejection fraction(LVEF)in the patients with type 2 diabetes and acute coronary syndrome (ACS). Methods The population of this cross-sectional study included 2377 inpatients with type 2 diabetes who had an ACS admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2016 to January 2021. Results Diabetic patients with ACS were divided into 2 subgroups based on LVEF. The mean SOD activity was significantly lower in patients with an LVEF ≤ 45% than in those with an LVEF > 45% (149.1 (146.4, 151.9) versus 161.9 (160.8, 163.0)). Using ROC statistic, a cut-off value of 148.8 U/ml indicated an LVEF ≤ 45% with a sensitivity of 51.6% and a specificity of 73.7%. SODs activity were found to be correlated with the levels of NT-proBNP, hs-cTnT, the inflammatory marker CRP and fibrinogen. Despite taking the lowest quartile as a reference (OR 0.368, 95% CI 0.493–0.825, P = 0.001) or examining 1 normalized unit increase (OR 0.651, 95% CI 0.482–0.880, P = 0.005), SOD activity was found to be a stronger predictor of reduced LVEF than CRP and fibrinogen, independent of confounding factors. Conclusions Our cross-sectional study suggests that SOD activity might be a valuable and easily accessible tool for assessing and monitoring reduced LVEF in the diabetic patients with ACS.

Group 1 innate lymphoid cells (ILCs) comprise conventional natural killer (cNK) cells and type 1 innate lymphoid cells (ILC1s). The main functions of liver cNK cells and ILC1s not only include directly killing target cells but also regulating local immune microenvironment of the liver through the secretion of cytokines. Uncovering the intricate mechanisms by which transcriptional factors regulate and influence the functions of liver cNK cells and ILC1s, particularly within the context of liver tumors, presents a significant opportunity to amplify the effectiveness of immunotherapies against liver malignancies. Using Ncr1-drived conditional knockout mouse model, our study reveals the regulatory role of Prdm1 in shaping the composition and maturation of cNK cells. Although Prdm1 did not affect the killing function of cNK cells in an in vivo cytotoxicity model, a significant increase in cancer metastasis was observed in Prdm1 knockout mice. Interferon-gamma (IFN-γ), granzyme B, and perforin secretion decreased significantly in Prdm1-deficient cNK cells and liver ILC1s. Single-cell RNA sequencing (scRNA-seq) data also provided evidences that Prdm1 maintains functional subsets of cNK cells and liver ILC1s and facilitates communications between cNK cells, liver ILC1s, and macrophages. The present study unveiled a novel regulatory mechanism of Prdm1 in cNK cells and liver ILC1s, showing promising potential for developing innovative immune therapy strategies against liver cancer.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease of unknown origin and the most common interstitial lung disease. However, therapeutic options for IPF are limited, and novel therapies are urgently needed. Histone deacetylases (HDACs) are enzymes that participate in balancing histone acetylation activity for chromatin remodeling and gene transcription regulation. Increasing evidence suggests that the HDAC family is linked to the development and progression of chronic fibrotic diseases, including IPF. This review aims to summarize available information on HDACs and related inhibitors and their potential applications in treating IPF. In the future, HDACs may serve as novel targets, which can aid in understanding the etiology of PF, and selective inhibition of single HDACs or disruption of HDAC genes may serve as a strategy for treating PF.

Pteroceltis tatarinowii Maxim is a famous paper-making tree endemic to China with a wide distribution. Leaves of this tree growing in different habitats show a certain plasticity, which is important for their ecological adaption. Here, the photosynthesis ability, hydraulic properties, and anatomy of P. tatarinowii leaves from a limestone forest (Langya Mountain) and a cultivated forest (Xiaoling Village) in Anhui province were compared. The results showed that leaves from Xiaoling Village had higher net photosynthesis rate and hydraulic conductivity, which were closely related to their higher vein density, stomatal density and palisade tissue thickness than leaves from Langya Mountain. However, lower leaf water potentials at turgor loss point and at 50% loss of conductivity, as well as a higher leaf hardness, for Langya Mountain leaves indicated their higher hydraulic safety and drought resistance than those of leaves from Xiaoling Village. This study reveals a hydraulic trade-off between efficiency and safety for P. tatarinowii leaves growing in distinct habitats. Further studies should include more habitats and different vegetation communities to clarify the ecological adaption so as to provide a scientific basis for the protection of this species.

Abstract Background Studies on sleep problems among caregivers of psychiatric patients, especially during the COVID-19 pandemic, are limited. This study examined the prevalence and correlates of insomnia symptoms (insomnia hereafter) among caregivers of psychiatric inpatients during the COVID-19 pandemic as well as the association with quality of life (QoL) from a network analysis perspective. Methods A multi-center cross-sectional study was conducted on caregivers of inpatients across seven tertiary psychiatric hospitals and psychiatric units of general hospitals. Network analysis explored the structure of insomnia using the R program. The centrality index of “Expected influence” was used to identify central symptoms in the network, and the “flow” function was adopted to identify specific symptoms that were directly associated with QoL. Results A total of 1,101 caregivers were included. The overall prevalence of insomnia was 18.9% (n = 208; 95% CI = 16.7–21.3%). Severe depressive (OR = 1.185; P

Abstract Purpose Bulimia nervosa (BN) is characterized by recurrent binge-eating episodes and inappropriate compensatory behaviors. This study investigated alterations in resting-state surface-based neural activity in BN patients and explored correlations between brain activity and eating behavior. Methods A total of 26 BN patients and 28 healthy controls were enrolled. Indirect measurement of cerebral cortical activity and functional connectivity (FC) analyses were performed in Surfstat. A principal component analysis (PCA) model was used to capture the commonalities within the behavioral questionnaires from the BN group. Results Compared with the healthy control group, the BN group showed decreased surface-based two-dimensional regional homogeneity in the right superior parietal lobule (SPL). Additionally, the BN group showed decreased FC between the right SPL and the bilateral lingual gyrus and increased FC between the right SPL and the left caudate nucleus and right putamen. In the FC–behavior association analysis, the second principal component (PC2) was negatively correlated with FC between the right SPL and the left caudate nucleus. The third principal component (PC3) was negatively correlated with FC between the right SPL and the left lingual gyrus and positively correlated with FC between the right SPL and the right lingual gyrus. Conclusion We revealed that the right SPL undergoes reorganization with respect to specific brain regions at the whole-brain level in BN. In addition, our results suggest a correlation between brain reorganization and maladaptive eating behavior. These findings may provide useful information to better understand the neural mechanisms of BN. Level of evidence V, descriptive study.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible interstitial lung disease with a prognosis worse than lung cancer. It is a fatal lung disease with largely unknown etiology and pathogenesis, and no effective therapeutic drugs render its treatment largely unsuccessful. With continuous in-depth research efforts, the epigenetic mechanisms in IPF pathogenesis have been further discovered and concerned. As a widely studied mechanism of epigenetic modification, DNA methylation is primarily facilitated by DNA methyltransferases (DNMTs), resulting in the addition of a methyl group to the fifth carbon position of the cytosine base, leading to the formation of 5-methylcytosine (5-mC). Dysregulation of DNA methylation is intricately associated with the advancement of respiratory disorders. Recently, the role of DNA methylation in IPF pathogenesis has also received considerable attention. DNA methylation patterns include methylation modification and demethylation modification and regulate a range of essential biological functions through gene expression regulation. The Ten-Eleven-Translocation (TET) family of DNA dioxygenases is crucial in facilitating active DNA demethylation through the enzymatic conversion of the modified genomic base 5-mC to 5-hydroxymethylcytosine (5-hmC). TET2, a member of TET proteins, is involved in lung inflammation, and its protein expression is downregulated in the lungs and alveolar epithelial type II cells of IPF patients. This review summarizes the current knowledge of pathologic features and DNA methylation mechanisms of pulmonary fibrosis, focusing on the critical roles of abnormal DNA methylation patterns, DNMTs, and TET proteins in impacting IPF pathogenesis. Researching DNA methylation will enchance comprehension of the fundamental mechanisms involved in IPF pathology and provide novel diagnostic biomarkers and therapeutic targets for pulmonary fibrosis based on the studies involving epigenetic mechanisms.

Abstract Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti‐inflammatory macrophages, there are few researches on targeting pro‐inflammatory macrophages, which is partially attributed to their non‐s pecificity phagocytosis of extracellular substances. In this study, a novel recombinant protein is constructed that can be anchored on an exosome membrane with the purpose of targeting pro‐inflammatory macrophages via antigen recognition, which is named AnCar‐ExoLaIMTS. The data indicate that the phagocytosis efficiencies of pro‐inflammatory macrophages for different AnCar‐ExoLaIMTS show obvious differences. The AnCar‐ExoLaIMTS3 has the best targeting ability for pro‐inflammatory macrophages in vitro and in vivo. Mechanically, AnCar‐ExoLaIMTS3 can specifically recognize the leucine‐rich repeat domain of the TLR4 receptor, and then enter into pro‐inflammatory macrophages via the TLR4‐mediated receptor endocytosis pathway. Moreover, AnCar‐ExoLaIMTS3 can efficiently deliver therapeutic cargo to pro‐inflammatory macrophages and inhibit the synovial inflammatory response via downregulation of HIF‐1α level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro‐inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases.

ObjectiveThe coronavirus disease (COVID-19) and the public health responses were associated with a huge health burden, which could influence sleep quality. This meta-analysis and systematic review examined the prevalence of poor sleep quality in COVID-19 patients.MethodsPubMed, Web of Science, Embase, and PsycINFO were systematically searched from their respective inception to October 27, 2022. Prevalence rates of poor sleep were analyzed using a random effects model.ResultsTotally, 24 epidemiological and 12 comparative studies with 8,146 COVID-19 patients and 5,787 healthy controls were included. The pooled prevalence of poor sleep quality based on the included studies was 65.0% (95%CI: 59.56–70.44%, I2 = 97.6%). COVID-19 patients had a higher risk of poor sleep quality compared to healthy controls (OR = 1.73, 95% CI: 1.30–2.30, p

N-methyl-d-aspartate (NMDA) receptor (NMDAR) activation mediates glutamate (Glu) toxicity and involves bleomycin (BLM)-induced acute lung injury (ALI). We have reported that bone marrow-derived mesenchymal stem cells (BM-MSCs) are NMDAR-regulated target cells, and NMDAR activation inhibits the protective effect of BM-MSCs on BLM-induced pulmonary fibrosis, but its effect on ALI remains unknown. Here, we found that Glu release was significantly elevated in plasma of mice at d 7 after intratracheally injected with BLM. BM-MSCs were pretreated with NMDA (the selective agonist of NMDAR) and transplanted into the recipient mice after the BLM challenge. BM-MSCs administration significantly alleviated the pathological changes, inflammatory response, myeloperoxidase activity, and malondialdehyde content in the damaged lungs, but NMDA-pretreated BM-MSCs did not ameliorate BLM-induced lung injury in vivo. Moreover, NMDA down-regulated prostaglandin E2 (PGE2) secretion and cyclooxygenase (COX)-2 expression instead of COX-1 expression in BM-MSCs in vitro. We also found that NMDAR1 expression was increased and COX-2 expression was decreased, but COX-1 expression was not changed in primary BM-MSCs of BLM-induced ALI mice. Further, the cultured supernatants of lipopolysaccharide (LPS)-pretreated RAW264.7 macrophages were collected to detect inflammatory factors after co-culture with NMDA-pretreated BM-MSCs. The co-culture experiments showed that NMDA precondition inhibited the anti-inflammatory effect of BM-MSCs on LPS-induced macrophage inflammation, and PGE2 could partially alleviate this inhibition. Our findings suggest that NMDAR activation attenuated the protective effect of BM-MSCs on BLM-induced ALI in vivo. NMDAR activation inhibited COX-2 expression and PGE2 secretion in BM-MSCs and weakened the anti-inflammatory effect of BM-MSCs on LPS-induced macrophage inflammation in vitro. In conclusion, NMDAR activation attenuates the protective effect of BM-MSCs on BLM-induced ALI via the COX-2/PGE2 pathway. Keywords: Acute Lung Injury, BM-MSCs, NMDA receptor, COX-1/2, PGE2.

Objective To construct and internally validate a nomogram that predicts the likelihood of postoperative delirium in a cohort of elderly individuals undergoing hip arthroplasty.Methods Data for a total of 681 elderly patients underwent hip arthroplasty were retrospectively collected and divided into a model (n = 477) and a validation cohort (n = 204) according to the principle of 7:3 distribution temporally. The assessment of postoperative cognitive function was conducted through the utilization of The Confusion Assessment Method (CAM). The nomogram model for postoperative cognitive impairments was established by a combination of Lasso regression and logistic regression. The receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) were used to evaluate the performance.Results The nomogram utilized various predictors, including age, body mass index (BMI), education, preoperative Barthel Index, preoperative hemoglobin level, history of diabetes, and history of cerebrovascular disease, to forecast the likelihood of postoperative delirium in patients. The area under the ROC curves (AUC) for the nomogram, incorporating the aforementioned predictors, was 0.836 (95% CI: 0.797–0.875) for the training set and 0.817 (95% CI: 0.755–0.880) for the validation set. The calibration curves for both sets indicated a good agreement between the nomogram’s predictions and the actual probabilities.Conclusion The use of this novel nomogram can help clinicians predict the likelihood of delirium after hip arthroplasty in elderly patients and help prevent and manage it in advance.

Cancer poses a substantial risk to human life and wellbeing as a result of its elevated incidence and fatality rates. Endoplasmic reticulum stress (ERS) is an important pathway that regulates cellular homeostasis. When ERS is under- or overexpressed, it activates the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK)-, inositol-requiring enzyme 1 (IRE1)- and activating transcription Factor 6 (ATF6)-related apoptotic pathways to induce apoptosis. Tumor cells and microenvironment are susceptible to ERS, making the modulation of ERS a potential therapeutic approach for treating tumors. The use of natural products to treat tumors has substantially progressed, with various extracts demonstrating antitumor effects. Nevertheless, there are few reports on the effectiveness of natural products in inducing apoptosis by specifically targeting and regulating the ERS pathway. Further investigation and elaboration of its mechanism of action are still needed. This paper examines the antitumor mechanism of action by which natural products exert antitumor effects from the perspective of ERS regulation to provide a theoretical basis and new research directions for tumor therapy.

Abstract Background The effects of traumatic brain injury (TBI) can include physical disability and even death. The development of effective therapies to promote neurological recovery is still a challenging problem. 3D-printed biomaterials are considered to have a promising future in TBI repair. The injury-preconditioned secretome derived from human umbilical cord blood mesenchymal stem cells showed better stability in neurological recovery after TBI. Therefore, it is reasonable to assume that a biological scaffold loaded with an injury-preconditioned secretome could facilitate neural network reconstruction after TBI. Methods In this study, we fabricated injury-preconditioned secretome/collagen/heparan sulfate scaffolds by 3D printing. The scaffold structure and porosity were examined by scanning electron microscopy and HE staining. The cytocompatibility of the scaffolds was characterized by MTT analysis, HE staining and electron microscopy. The modified Neurological Severity Score (mNSS), Morris water maze (MWM), and motor evoked potential (MEP) were used to examine the recovery of cognitive and locomotor function after TBI in rats. HE staining, silver staining, Nissl staining, immunofluorescence, and transmission electron microscopy were used to detect the reconstruction of neural structures and pathophysiological processes. The biocompatibility of the scaffolds in vivo was characterized by tolerance exposure and liver/kidney function assays. Results The excellent mechanical and porosity characteristics of the composite scaffold allowed it to efficiently regulate the secretome release rate. MTT and cell adhesion assays demonstrated that the scaffold loaded with the injury-preconditioned secretome (3D-CH-IB-ST) had better cytocompatibility than that loaded with the normal secretome (3D-CH-ST). In the rat TBI model, cognitive and locomotor function including mNSS, MWM, and MEP clearly improved when the scaffold was transplanted into the damage site. There is a significant improvement in nerve tissue at the site of lesion. More abundant endogenous neurons with nerve fibers, synaptic structures, and myelin sheaths were observed in the 3D-CH-IB-ST group. Furthermore, the apoptotic response and neuroinflammation were significantly reduced and functional vessels were observed at the injury site. Good exposure tolerance in vivo demonstrated favorable biocompatibility of the scaffold. Conclusions Our results demonstrated that injury-preconditioned secretome/collagen/heparan sulfate scaffolds fabricated by 3D printing promoted neurological recovery after TBI by reconstructing neural networks, suggesting that the implantation of the scaffolds could be a novel way to alleviate brain damage following TBI. Graphical abstract

ObjectiveThe homeostasis of the immune system is influenced by the gut microbiota. Previous studies have reported dysbiosis in the gut microbiota of myasthenia gravis (MG) patients. To investigate potential alterations in gut microbiota and metabolites in newly diagnosed and untreated MG patients, we conducted a case-control study.MethodsFecal samples were collected from 11 newly diagnosed and untreated MG patients as well as 11 age-and sex-matched healthy controls. These samples underwent analysis for gut microbiota using 16S ribosomal RNA (rRNA) gene sequencing, while fecal metabolome was analyzed using liquid chromatography-electrospray tandem mass spectrometry system (LC-ESI-MS/MS).ResultsThe microbial community richness (observed species) and diversity (Shannon and Simpson indices) were significantly lower in the MG group compared to the control group. Microbiota composition analysis revealed significant differences between the MG and control groups at phylum, family, and genus levels. Linear discriminant analysis effect size (LEfSe) analysis showed a substantial decrease in abundance of the genus Faecalibacterium within the MG group. Fecal metabolome analysis identified three up-regulated metabolites involved in amino acid metabolism (taurine, creatinine, L-carnitine), one up-regulated metabolite involved in lipid metabolism (oleic acid), with correlation analysis indicating a positive association between Faecalibacterium abundance and creatinine levels.ConclusionOur findings suggest that dysbiosis already exists in newly diagnosed and untreated MG patients, implying that dysbiosis within the gut microbiota may be an initiating factor contributing to MG pathogenesis. Furthermore, F. prausnitzii may hold promise as a probiotic for treating MG.

Post-translational modification (PTM) refers to the covalent attachment of functional groups to protein substrates, resulting in structural and functional changes. PTMs not only regulate the development and progression of liver cancer, but also play a crucial role in the immune response against cancer. Cancer immunity encompasses the combined efforts of innate and adaptive immune surveillance against tumor antigens, tumor cells, and tumorigenic microenvironments. Increasing evidence suggests that immunotherapies, which harness the immune system’s potential to combat cancer, can effectively improve cancer patient prognosis and prolong the survival. This review presents a comprehensive summary of the current understanding of key PTMs such as phosphorylation, ubiquitination, SUMOylation, and glycosylation in the context of immune cancer surveillance against liver cancer. Additionally, it highlights potential targets associated with these modifications to enhance the response to immunotherapies in the treatment of liver cancer.

Abstract Background Stroke is the leading cause of disability worldwide, resulting in severe damage to the central nervous system and disrupting neurological functions. There is no effective therapy for promoting neurological recovery. Growing evidence suggests that the composition of exosomes from different microenvironments may benefit stroke. Therefore, it is reasonable to assume that exosomes secreted in response to infarction microenvironment could have further therapeutic effects. Methods In our study, cerebral infarct tissue extracts were used to pretreat umbilical cord mesenchymal stem cells (UCMSC). Infarct-preconditioned exosomes were injected into rats via tail vein after middle cerebral artery occlusion (MCAO). The effect of infarct-preconditioned exosomes on the neurological recovery of rats was examined using Tunel assay, 2,3,5-triphenyltetrazolium chloride (TTC) assay, magnetic resonance imaging (MRI) analyses, modified Neurological Severity Score (mNSS), Morris water maze (MWM), and vascular remodeling analysis. Mi-RNA sequencing and functional enrichment analysis were used to validate the signal pathway involved in the effect of infarct-preconditioned exosomes. Human umbilical vein endothelial cells (HUVECs) were co-cultured with the isolated exosomes. Cell Counting Kit-8 (CCK-8) assay, scratch healing, and Western blot analysis were used to detect the biological behavior of HUVECs. Results The results showed that compared with normal exosomes, infarct-preconditioned exosomes further promoted vascular remodeling and recovery of neurological function after stroke. The function of upregulated miRNAs and their target genes which is beneficial to vascular smooth muscle cells verified the importance of vascular remodeling in improving stroke. Better resistance to oxygen–glucose deprivation/reoxygenation (OGD/R), reduced apoptosis, and enhanced migration were observed in infarct-preconditioned exosomes-treated umbilical vein endothelial cells. Conclusions Our results demonstrated that infarct-preconditioned exosomes promoted neurological recovery after stroke by enhancing vascular endothelial remodeling, suggested that infarct-preconditioned exosomes could be a novel way to alleviate brain damage following a stroke.

BackgroundThere is a vast amount of evidence-based medicine research on the major depressive disorder (MDD) available in the literature, however, no studies on the overall performance, productivity and impact of such research have been published to date. This study explored and mapped the research outputs of MDD-related systematic reviews and meta-analyses (SR/MA) from a bibliometric perspective.MethodsRelevant data were retrieved with search terms on MDD, systematic review and meta-analysis.ResultsA total of 4,870 papers with 365,402 citations published from 1983 to 2022 were included in the analysis. The publication output has grown steadily over time with the most publications originating from the USA (1,020; 20.94%), the UK (516; 10.60%) and China (448; 9.20%). The research collaborations between countries were most frequent between the USA and UK (266; 5.46%). Journal of Affective Disorders (379; 7.78%) was the most productive journal, while Cuijpers P was the most productive author (121; 2.48%), and University of Toronto (569; 11.78%) was the most productive institution. The top 10 most cited articles on MDD-related SR/MA had citations ranging from 1,806 to 3,448. The high-frequency keywords were mainly clustered into four themes, including psychiatric comorbidities, clinical trials, treatment, and brain stimulation in MDD.ConclusionThe rapid increase in the number of SR/MA of MDD in recent years highlights the importance of this research field. Psychiatric comorbidities, clinical interventions, and treatment of MDD have been identified as hot topics, while biological mechanisms in MDD are likely to be an emerging research priority.

Rhabdomyosarcoma (RMS) is a prevalent form of soft tissue sarcoma that primarily affects children. Pediatric RMS is characterized by two distinct histological variants: embryonal (ERMS) and alveolar (ARMS). ERMS is a malignant tumor with primitive characteristics resembling the phenotypic and biological features of embryonic skeletal muscles. With the widespread and growing application of advanced molecular biological technologies, such as next-generation sequencing (NGS), it has been possible to determine the oncogenic activation alterations of many tumors. Specifically for soft tissue sarcomas, the determination of tyrosine kinase gene and protein related changes can be used as diagnostic aids and may be used as predictive markers for targeted tyrosine kinase inhibition therapy. Our study reports a rare and exceptional case of an 11-year-old patient diagnosed with ERMS, who tested positive for MEF2D-NTRK1 fusion. The case report presents a comprehensive overview of the clinical, radiographic, histopathological, immunohistochemical, and genetic characteristics of a palpebral ERMS. Furthermore, this study sheds light on an uncommon occurrence of NTRK1 fusion-positive ERMS, which may provide theoretical basis for therapy and prognosis.

BackgroundA growing number of studies has implicated oxidative stress in the pathophysiology of psychiatric disorders including schizophrenia. The aim of this study was to explore the field of schizophrenia and oxidative stress-related research from a bibliometric perspective.MethodsAll relevant publications on schizophrenia and oxidative stress were obtained from Web of Science Core Collection (WOSCC) database from its inception date to November 8, 2022. VOSviewer software was used to examine co-authorships and co-occurring keywords. R software was used to present the main characteristics of publications and cooperation frequency among countries. CiteSpace was used to investigate keywords with the strongest citation bursts.ResultsA total of 3,510 publications on schizophrenia and oxidative stress were included. The United States had the largest number of publications (26.1%), and international collaborations. University of Melbourne was the most productive institution, while Schizophrenia Research was the most productive journal in this field. Apart from “schizophrenia” and “oxidative stress”, the terms “prefrontal cortex”, “brain” and “nitric oxide” were among the most frequently used keywords.ConclusionsIn conclusion, research on the association between oxidative stress and schizophrenia has received growing attention in the academic literature that is expected to continue its upward trajectory during the next two decades. Existing research suggests there has been a transition from research focused on pathways to animal models, and subsequently to clinical applications. Intervention studies on oxidative stress and schizophrenia are likely to be an important focus of related work in the near future.

Freshwater fungi, growing on submerged wood, can promote the degradation of organisms and the reuse of rotten wood energy and play key roles in freshwater ecosystems. Here, a new hyphomycetous fungus, Sporidesmiella lignicola, was isolated and identified from submerged wood samples collected in a small stream in Jiangxi Province, south-eastern China.The new taxon was studied, based on morphological characters and phylogenetic analyses combined with LSU, ITS, TEF1α and RPB2 sequences data. Sporidesmiella lignicola was morphologically characterised by its pink colonies on PDA medium in prophase, macronematous, mononematous, solitary, brown, septate, unbranched, straight or slightly flexuous conidiophores with holoblastic, polyblastic, integrated, terminal, pale brown conidiogenous cells and cylindrical, narrowly clavate, broadly obovoid to cuneiform, 3–4-distoseptate, olivaceous brown or brown conidia with rounded apex. A phylogenetic tree was constructed, based on the combination of LSU, ITS, TEF1α and RPB2 sequences data.

Healthcare workers (HCWs) are considered both a high-risk population regarding infections and effective vaccine recommenders whose willingness to be vaccinated is the key to herd immunity. However, the vaccination status, acceptance, and knowledge of the 2019 coronavirus disease (COVID-19) vaccine among HCWs remain unknown. Therefore, we conducted an online survey regarding the above among HCWs in China after the vaccine was made available. Questionnaires returned by 1,779 HCWs were analyzed. Among these participants, 34.9% were vaccinated, 93.9% expressed their willingness to receive the COVID-19 vaccine, and vaccine knowledge level was high (89.2%). A bivariate analysis found that participants with a college degree, low level of knowledge, non-exposure to COVID-19 status, and those who are females or nurses have a lower vaccination rate, while participants who are married, with a monthly income of more than 5,000 yuan, and low knowledge levels are less willing to be vaccinated. A multivariate analysis found that participants with a high (OR = 7.042, 95% CI = 4.0918–12.120) or medium (OR = 3.709, 95% CI = 2.072–6.640) knowledge level about COVID-19 vaccines were more willing to be vaccinated. Participants were less likely to accept a COVID-19 vaccine if they were married (OR = 0.503, 95% CI = 0.310–0.815). In summary, Chinese HCWs have a strong willingness to be vaccinated and a high level of knowledge. Measures, such as targeted education for HCWs with low willingness and low level of knowledge, open vaccine review procedures, increased government trust, reduced vaccine costs, and provide vaccination guarantee policies, may improve the vaccination coverage of the at-risk group.

Abstract. Background:. Although congenital hypothyroidism (CH) has been widely studied in Western countries, CH incidence at different administrative levels in China during the past decade remains unknown. This study aimed to update the incidence and revealed the spatial pattern of CH incidence in the mainland of China, which could be helpful in the planning and implementation of preventative measures. Methods:. The data used in our study were derived from 245 newborns screening centers that cover 30 provinces of the Chinese Newborn Screening Information System. Spatial auto-correlation was analyzed by Global Moran I and Getis-Ord Gi statistics at the provincial level. Kriging interpolation methods were applied to estimate a further detailed spatial distribution of CH incidence at city level throughout the mainland of China, and Kulldorff space scanning statistical methods were used to identify the spatial clusters of CH cases at the city level. Results:. A total of 91,921,334 neonates were screened from 2013 to 2018 and 42,861 cases of primary CH were identified, yielding an incidence of 4.66 per 10,000 newborns screened (95% confidence interval [CI]: 4.62–4.71). Neonates in central (risk ratio [RR] = 0.84, 95% CI: 0.82–0.85) and western districts (RR = 0.71, 95% CI: 0.69–0.73) had lower probability of CH cases compared with the eastern region. The CH incidence indicated a moderate positive global spatial autocorrelation (Global Moran I value = 0.394, P

Abstract Triglyceride glucose (TyG) index and inflammatory markers are reported to have a positive association with metabolic syndrome (MetS). However, no previous study has assessed the value of TyG index and inflammatory markers as predictors of metabolic syndrome in the same study. This study looks at the comparison of the triglyceride index and blood leukocyte indices as predictors of metabolic syndrome in the Chinese population. The study cohort involved 1542 Chinese population without metabolic syndrome. The subjects underwent comprehensive routine health examination in 2011 and returned for a follow-up examination in 2016. Metabolic syndrome was defined according to Chinese Diabetes Society criteria, using body mass index for the replacement of waist circumference. TyG index, total leukocytes, neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio (NLR) were measured. Adjust d logistic models were used to assess the relationship between TyG index, blood leukocyte indices, and incident MetS. Receiver operating characteristic (ROC) curves were performed to determine the predictive value of TyG index and blood leukocyte indices for MetS. Results from multivariate logistic regression analysis showed that, in the adjusted model, the subjects with the highest quartile of TyG index and neutrophils had a 3.894- and 1.663-fold increased incidence of MetS (P

ObjectivesThe growing rate of retraction of scientific publications has attracted much attention within the academic community, but there is little knowledge about the nature of such retractions in schizophrenia-related research. This study aimed to analyze the characteristics of retractions of schizophrenia-related publications.Materials and methodsThe Web of Science was searched for eligible studies. A bibliometric analysis was conducted to describe the characteristics of the retractions using R software and Excel 2019. Content analysis was conducted to examine the essential components of retraction notices.ResultsA total of 36 retracted publications with 415 citations were identified from 1997 to 2021, of which, 83.3% occurred in the last decade. The overall retraction rate was 0.19%, with most of them (29; 80.56%) from the United Kingdom. The retractions were published in 33 journals, and the 2020 IFs ranged between 0.17 and 49.96 (Median = 3.93). The retractions involved 21 research areas, particularly in Psychiatry (19; 52.78%), Neurosciences and Neurology (10; 27.78%), and Psychology (7; 19.44%). Data issues (17; 42.22%), administrative errors of the publishers (5; 13.89%), and study design (4; 11.11%) were the top three reasons for retractions.ConclusionThis study provides an insight into retractions of schizophrenia-related publications. Institutional governance should be further strengthened to improve the scrutiny of publications, prevent continuing citations, and erroneous propagation after retraction.

Brain structural and functional abnormalities have been shown to be involved in the neurobiological underpinnings of bulimia nervosa (BN), while the mechanisms underlying this dysregulation are unclear. The main goal of this investigation was to explore the presence of brain structural alterations and relevant functional changes in BN. We hypothesized that BN patients had regional gray matter volume abnormalities and corresponding resting-state functional connectivity (rsFC) changes compared with healthy controls. Thirty-one BN patients and twenty-eight matched healthy controls underwent both high-resolution T1-weighted magnetic resonance imaging (MRI) and resting-state functional MRI. Structural analysis was performed by voxel-based morphometry (VBM), with subsequent rsFC analysis applied by a seed-based, whole-brain voxelwise approach using the abnormal gray matter volume (GMV) region of interest as the seed. Compared with the controls, the BN patients showed increased GMV in the left medial orbitofrontal cortex (mOFC). The BN patients also exhibited significantly increased rsFC between the left mOFC and the right superior occipital gyrus (SOG) and decreased rsFC between the left mOFC and the left precentral gyrus, postcentral gyrus, and supplementary motor area (SMA). Furthermore, the z values of rsFC between the left mOFC and right SOG was positively correlated with the Dutch Eating Behavior Questionnaire-external eating scores. Findings from this investigation further suggest that the mOFC plays a crucial role in the neural pathophysiological underpinnings of BN, which may lead to sensorimotor and visual regions reorganization and be related to representations of body image and the drive behind eating behavior. These findings have important implications for understanding neural mechanisms in BN and developing strategies for prevention.

Revealing the mechanisms of neural development and the pathogenesis of neural diseases are one of the most challenging missions in life science. Pluripotent stem cells derived brain organoids mimic the development, maturation, signal generation, and function of human brains, providing unique advantage for neurology. Single-cell RNA sequencing (scRNA-Seq) and multielectrode array independently revealed the similarity between brain organoids and immature human brain at early developmental stages, in the context of gene transcription and dynamic network of neuronal signals. Brain organoids provided the unique opportunity to investigate the underlying mechanism of neural differentiation, senescence, and pathogenesis. In this review, we summarized the latest knowledge and technology in the brain organoid field, the current and potential applications in disease models and pre-clinic studies, with emphasizing the importance of transcriptional and epigenetic analysis.

Abstract. Atopic dermatitis (AD) is a common disease clinically characterized by chronic recurrent eczematous lesions, dry skin, and pruritus. AD can negatively impact patients’ quality of life. The prevalence of AD in China has been increasing during the past few decades. Based on the most recent advances in the treatment of AD, we updated the 2014 version of the Guidelines for Diagnosis and Treatment of Atopic Dermatitis in China regarding the definition, epidemiology, pathogenesis, clinical classification, diagnosis, prevention, and treatment of AD.

Abstract Background Yunnan Province was considered the most difficult place in China for malaria elimination because of its complex malaria epidemiology, heterogeneous ecological features, relatively modest economic development, and long, porous border with three malaria endemic countries: Lao People’s Democratic Republic, Myanmar, and Viet Nam. Methods Academic publications and grey literature relevant to malaria elimination in Yunnan covering the period from 1950 until 2020 inclusive were considered. The following academic indexes were searched: China Science Periodical Database, China National Knowledge Infrastructure Database, and MEDLINE. Grey literature sources were mainly available from the National Institute of Parasitic Diseases (NIPD), the Chinese Center for Diseases Control and Prevention, and the Yunnan Institute of Parasitic Diseases (YIPD). Results A malaria elimination campaign in the 1950–1960s, based mainly on mass administration of antimalarial drugs and large-scale vector control, reduced morbidity and mortality from malaria and interrupted transmission in some areas, although elimination was not achieved. Similar strategies were used to contain outbreaks and a resurgence of disease during the 1970s, when malaria services were discontinued. From the 1980s, malaria incidence declined, despite the challenges of large numbers of mobile and migrant populations and an unstable primary health care system in rural areas following economic transformation. Launch of the national malaria elimination programme in 2010 led to adoption of the ‘1–3-7′ surveillance and response strategy specifying timely detection of and response for every case, supported by the establishment of a real-time web-based disease surveillance system and a new primary health care system in rural areas. Border malaria was addressed in Yunnan by strengthening the surveillance system down to the lowest level, cross-border collaboration with neighbouring countries and non-governmental organizations, and the involvement of other sectors. Conclusions Seven decades of work to eliminate malaria in Yunnan have shown the importance of political commitment, technically sound strategies with high quality implementation, a robust surveillance and response system at all levels, community participation and effective management of border malaria. The experiences and lessons learned from elimination remain important for prevention re-establishment of malaria transmission in the Province.

Abstract Background Globally, malaria is still a major public health challenge. Drug-based treatment is the primary intervention in malaria control and elimination. However, optimal use of mass or targeted treatments remains unclear. A variety of radical, preventive and presumptive treatment regimens have been administrated in China and a systematic review was conducted to evaluate effectiveness, and discuss experiences, limitations, and lessons learnt in relation to the use of these regimens. Methods The search for information includes both paper documents, such as books, malaria control annals and guidelines for malaria prevention and treatment, as well as three computer-based databases in Chinese (CNKI, WanFangdata and Xueshu.baidu) and two databases in English (PubMed and Google Scholar), to identify original articles and reports associated with drug administration for malaria in China. Results Starting from hyperendemicity to elimination of malaria in China, a large number of radical, preventive and presumptive treatment regimens had been tried. Those effective regimens were scaled up for malaria control and elimination programmes in China. Between 1949 and 1959, presumptive treatment with available anti-malarial drugs was given to people with enlarged spleens and those who had symptoms suggestive of malaria within the last 6 months. Between 1960 and 1999, mass drug administration (MDA) was given for preventive and radical treatment. Between 2000 and 2009, the approach was more targeted, and drugs were administed only to prevent malaria infection in those at high risk of exposure and those who needed radical treatment for suspected malaria. Presumptive therapy was only given to febrile patients. From 2010, the malaria programme changed into elimination phase, radical treatment changed to target individuals with confirmed either Plasmodium vivax or Plasmodium ovale within the last year. Preventive treatment was given to those who will travel to other endemic countries. Presumptive treatment was normally not given during this elimination phase. All cases of suspected were confirmed by either microscopy or rapid diagnosis tests for malaria antigens before drugs were administered. The engagement of the broader community ensured high coverage of these drug-based interventions, and the directly-observed therapy improved patient safety during drug administration. Conclusion A large number of radical, preventive and presumptive treatment regimens for malaria had been tried in China with reported success, but the impact of drug-based interventions has been difficult to quantify because they are just a part of an integrated malaria control strategy. The historical experiences of China suggest that intervention trials should be done by the local health facilities with community involvement, and a local decision is made according to their own trial results.

Abstract Background In order to reduce the burden on organ shortage around the world, using potential infectious donor might be an option. However, scarce evidences have been published on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg) + donors to HBsAg- recipients [D (HBsAg+)/R(HBsAg-)] without hepatitis B virus (HBV) immunity. Here, we reported the results of D(HBsAg+/HBV DNA- or +)/R(HBsAg-) living KTx recipients with or without HBV immunity. Methods We retrospectively identified 83 D(HBsAg+)/R(HBsAg-) living KTx recipients, and 83 hepatitis B core antibody (HBcAb) + living donors to HBcAb- recipients [D(HBcAb+)/R(HBcAb-)] were used as control group by reviewing medical archives and propensity score matching. Treatment failure (defined as any HBV serology conversion, liver injury, graft loss, or recipient death) is the primary endpoint. Results Twenty-four donors (28.9%) were HBV DNA+, and 20 recipients had no HBV immunity in the D(HBsAg+)/R(HBsAg-) group pre-transplantation. HBV prophylaxis was applied in all D(HBsAg+)/R(HBsAg-) recipients, while none was applied in the D(HBcAb+)/R(HBcAb-) group. We observed a significant higher treatment failure in D(HBsAg+)/R(HBsAg-) than D(HBcAb+)/R(HBcAb-) group (21.7% vs. 10.8%, P

BackgroundSchizophrenia (SCZ) is a severe psychiatric disorder that involves inflammatory processes. The aim of this study was to explore the field of inflammation-related research in SCZ from a bibliometric perspective.MethodsRegular and review articles on SCZ- and inflammation-related research were obtained from the Web of Science Core Collection (WOSCC) database from its inception to February 19, 2022. R package “bibliometrix” was used to summarize the main findings, count the occurrences of the top keywords, visualize the collaboration network between countries, and generate a three-field plot. VOSviewer software was applied to conduct both co-authorship and co-occurrence analyses. CiteSpace was used to identify the top references and keywords with the strongest citation burst.ResultsA total of 3,596 publications on SCZ and inflammation were included. Publications were mainly from the USA, China, and Germany. The highest number of publications was found in a list of relevant journals. Apart from “schizophrenia” and “inflammatory”, the terms “bipolar disorder,” “brain,” and “meta-analysis” were also the most frequently used keywords.ConclusionsThis bibliometric study mapped out a fundamental knowledge structure consisting of countries, institutions, authors, journals, and articles in the research field of SCZ and inflammation over the past 30 years. The results provide a comprehensive perspective about the wider landscape of this research area.

ObjectivesBoth bullying and psychosis-like experiences (PLEs) have gained much attention in recent years, but their interactions are not fully unraveled. The aim of the current study was to validate the Chinese version of Bullying Scale for Adults (C-BSA), and to investigate whether past bullying experiences independently predict the presence of PLEs in university students.MethodsThe validity and reliability of the C-BSA were determined in two independent samples. A battery of psychological inventories was also administered to assess the presence of PLEs, maltreatment history in the family, and current depression and anxiety, including the 15-item positive subscale of the community assessment of psychic experiences (CAPE-p15), the Chinese version of the Childhood Trauma Questionnaire (CTQ), Self-Rating Depression Scale (SDS), and Self-Rating Anxiety Scale (SAS).ResultsIn the construction sample (N = 629), a Cronbach's α of 0.921 indicated a good internal consistency of C-BSA. The exploratory factor analysis (EFA) yielded a four-factor model and a three-factor model, and both were verified by using the confirmatory factorial analysis (CFA) in the validation sample (N = 629). The total scores of C-BSA were significantly correlated with that of CTQ, CAPE-p15, SDS, and SAS. Multivariate logistic regression revealed that bullying was associated with 2.0 or 3.7 times of risk for the presence of PLEs (numbers of bullying types < = 3 or > 3, respectively) after controlling for CTQ, SDS, and SAS scores.ConclusionsC-BSA has shown good psychometric properties in college students. The contribution of past bullying experiences to the present PLEs seems to be independent of other childhood trauma, current depression, and anxiety.