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Abstract The metaphor is a pervasive linguistic device that has become an active research topic in the computer field because of its essential role in language's cognitive and communicative processes. Currently, the rapid expansion of social media encourages the development of multimodal. As the most popular communication method in social media, memes have attracted the attention of many linguists, who believe that metaphors contain rich metaphorical information. However, multimodal metaphor detection suffers from insufficient information due to the short text of memes and lacks effective multimodal fusion methods. To address these problems, we utilize a single-pass non-autoregressive text generation method to convert images into text to provide additional textual information for the model. In addition, the information of different modes is fused by a multi-layer fusion module consisting of a prefix guide module and a similarity-aware aggregator. The module can reduce the heterogeneity between modes, learn fine-grained information, and better integrate the characteristic information of different modes. We conducted many experiments on the Met-Meme dataset. Compared with the strong baseline model in the experiment, the weighted F1 of our model on three data types of the MET-Meme dataset improved by 1.95%, 1.55%, and 1.72%, respectively. To further demonstrate the effectiveness of the proposed method, we also conducted experiments on a multimodal sarcasm dataset and obtained competitive results.

Abstract Gliomas, particularly glioblastoma (GBM), are highly aggressive brain tumors with poor prognosis and high recurrence rates. This underscores the urgent need for novel therapeutic approaches. One promising target is Focal adhesion kinase (FAK), a key regulator of tumor progression currently in clinical trials for glioma treatment. Drug development, however, is both challenging and costly, necessitating efficient strategies. Computer-Aided Drug Design (CADD), especially when combined with machine learning (ML), streamlines the processes of virtual screening and optimization, significantly enhancing the efficiency and accuracy of drug discovery. Our study integrates ML, docking analysis, ADMET (absorption, distribution, metabolism, elimination, and toxicity) studies to identify novel FAK inhibitors specific to GBM. Predictive models showed strong performance, with an R2 of 0.892, MAE of 0.331, and RMSE of 0.467 using protein-level IC50 data in combined CDK, CDK extended fingerprints, and substructure fingerprint counts derived from 1280 FAK inhibitors. Another model, based on IC50 data from 2608 compounds tested on U87-MG cells, achieved an R2 of 0.789, MAE of 0.395, and RMSE of 0.536. Using these models, we efficiently identified 275 potentially active compounds out of 5107 candidates. Subsequent ADMET analysis narrowed this down to 16 potential FAK inhibitors that meet the established drug-likeness criteria. Moreover, molecular dynamics (MD) simulations validated the stable binding interactions between the selected compounds and the FAK protein. This study highlights the effectiveness of combining ML, docking analysis, and ADMET studies to rapidly identify potential FAK inhibitors from large databases, providing valuable insights for the systematic design of FAK inhibitors.

ObjectiveThis study aims to discuss the dose-response relationship between the Life's Essential 8 (LE8) score and chronic obstructive pulmonary disease (COPD).MethodsWe screened data from the National Health and Nutrition Examination Survey (NHANES) database for the years 2007–2018. Logistics regression analysis and subgroup analysis were used to explore the relationship between cardiovascular health (CVH) and COPD based on the LE8 score. Additionally, restricted cubic spline (RCS) plots were drawn to visually display the dose-response relationship.ResultsA total of 12,517 participants were included, of which 835 had COPD. After multivariable adjustment, the LE8 score was found to be linearly and inversely associated with the risk of developing COPD. A similar relationship was observed in the scores for health behavior factors, whereas the relationship was weaker for health factors. The RCS plots visually demonstrated the aforementioned dose-response relationship. Moreover, subgroup analyses showed that this relationship remained robust across different groups.ConclusionLE8 scores are inversely and linearly associated with the risk of developing COPD. Higher LE8 scores can reduce the risk of developing COPD in individuals over 40 years old, especially concerning health behavior factors.

Background Primary pulmonary diffuse large B-cell lymphoma (PP-DLBCL) is a rare extranodal non-Hodgkin's lymphoma (EN-NHL). Its prognosis as an aggressive lymphoma is abysmal, and predictive models are still lacking.Methods We screened patients diagnosed with PP-DLBCL between 2010 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. Then, univariate and multivariate COX regression analyses were used to identify independent risk factors affecting patient prognosis. Finally, a novel nomogram was constructed and the model was evaluated by looking at three dimensions.Results A total of 831 patients were included in this study. Most of the patients were elderly (526 (63.8%)) and female (428 (51.9%)). The included patients were randomized in a 7:3 ratio into a training group (577 (70%)) and a validation group (248 (30%)). We concluded that the independent risk factors of prognosis were age, extrapulmonary metastasis, radiotherapy, chemotherapy, and surgical intervention. The results of receiver operating characteristic curves, calibration curves, and decision curve analysis in the training and validation groups confirmed that the risk prediction nomogram could accurately predict the survival of PP-DLBCL.Conclusion This study is the first large population-based clinical data study on PP-DLBCL. A novel predictive model about prognosis has been developed to help clinical decision-making.

Abstract Background Uveal melanoma (UM), the most common adult intraocular tumor, is characterized by high malignancy and poor prognosis in advanced stages. Angiogenesis is critical for UM development, however, not only the role of vascular endothelial dysfunction in UM remains unknown, but also their analysis at the single-cell level has been lacking. A comprehensive analysis is essential to clarify the role of the endothelium in the development of UM. Methods By using single-cell RNA transcriptomics data of 11 cases of primary and liver metastasis UM, we analyzed the endothelial cell status. In addition, we analyzed and validated ECs in the in vitro model and collected clinical specimens. Subsequently, we explored the impact of endothelial dysfunction on UM cell migration and explored the mechanisms responsible for the endothelial cell abnormalities and the reasons for their peripheral effects. Results UM metastasis has a significantly higher percentage of vascular endothelial cells compared to in situ tumors, and endothelial cells in metastasis show significant senescence. Senescent endothelial cells in metastatic tumors showed significant Krüppel-like factor 4 (KLF4) upregulation, overexpression of KLF4 in normal endothelial cells induced senescence, and knockdown of KLF4 in senescent endothelium inhibited senescence, suggesting that KLF4 is a driver gene for endothelial senescence. KLF4-induced endothelial senescence drove tumor cell migration through a senescence-associated secretory phenotype (SASP), of which the most important component of the effector was CXCL12 (C-X-C motif chemokine ligand 12), and participated in the composition of the immunosuppressive microenvironment. Conclusion This study provides an undesirable insight of senescent endothelial cells in promoting UM metastasis.

BackgroundCoal workers' pneumoconiosis (CWP) is a serious occupational lung disease and one of the prescript occupational diseases in China. Epithelial-mesenchymal transition (EMT) is involved in the diffuse fibrosis of lung tissue of pneumoconiosis patients, and its mechanism may be related to the polarization of macrophages regulated by let-7c.ObjectiveTo investigate the effect of let-7c on the regulation of macrophage polarization in EMT in rats induced by coal dust exposure with different content of free SiO2.MethodsSD rats were randomly divided into a control group, a 5% SiO2 group, a 30% SiO2 group, and a 99.9% SiO2 group, with 16 rats in each group. The rats in each group were tracheally titrated with 100 μL of 20 mg·mL−1 suspension (5% SiO2, 30% SiO2, and 99.9% SiO2) or normal saline, respectively. Alveolar lavage fluid was collected at the ends of the 1st month and the 3rd month. The relative expression levels of M1 or M2 markers, CD86 or CD206, in alveolar macrophages (AMs) were detected by immunofluorescence. The inflammation and fibrosis of lung tissue were observed by hematoxylin-eosin (HE) staining and Masson staining. The expression levels of transforming growth factor-β1 (TGF-β1), E-cadherin, and vimentin were detected by Western blotting. The expression levels of let-7c and c/EBP-δ genes were detected by real-time fluorescence quantitative PCR.ResultsThe HE and Masson staining results showed that compared with the control group, the degree of pulmonary fibrosis in the 5% SiO2 group, the 30% SiO2 group, and the 99.9% SiO2 group gradually increased with the increase of dust exposure time. Compared with the control group, the expressions of CD86 and CD206 in the 5% SiO2 group, the 30% SiO2 group, and the 99.9% SiO2 group gradually increased at the end of the 1st month (F=330.904, 146.801, P

Abstract Sanghuangporus vaninii is a traditional edible and medicinal fungi with a long history in China. Recent studies have focused on its potential in treating diabetes, although the underlying mechanism remains unclear. This study aimed to investigate the antidiabetic and hypolipidemic effects of the formula of S. vaninii compounds (SVC) in diabetic mice and explore the potential improvement in the intestinal microbiota. Oral administration of SVC significantly reduced fasting blood glucose and improved insulin sensitivity and lipid indexes. In addition to its direct effects on glucose levels and insulin sensitivity, SVC was found to have an impact on the intestinal microbiota. The levels of short‐chain fatty acids receiving SVC intervention increased, and 16S rRNA sequencing revealed changes in the abundances of certain bacteria, such as Harryflintia, Helicobacter, Candidatus_Soleaferrea, Klebsiella, and Candidatus_Stoquefichus. These bacteria were found to be negatively associated with glucose and lipid indexes and positively related to body weight and insulin sensitivity. Overall, this study highlights the potential of SVC in treating diabetes and provides a novel perspective for understanding its antidiabetic mechanism through modulation of the intestinal microbiota.

Abstract Cellular senescence, one of the hallmarks of cancer, is characterized by cell cycle arrest and the loss of most normal cellular functions while acquiring a hypersecretory, proinflammatory phenotype. The function of senescent cells in cancer cells varies depending on the cellular conditions. Before the occurrence of cancer, senescent cells act as a barrier to prevent its development. But once cancer has occurred, senescent cells play a procancer role. However, few of the current studies have adequately explained the diversity of cellular senescence across cancers. Herein, we concluded the latest intrinsic mechanisms of cellular senescence in detail and emphasized the senescence‐associated secretory phenotype as a key contributor to heterogeneity of senescent cells in tumor. We also discussed five kinds of inducers of cellular senescence and the advancement of senolytics in cancer, which are drugs that tend to clear senescent cells. Finally, we summarized the various effects of senescent cells in different cancers and manifested that their functions may be diametrically opposed under different circumstances. In short, this paper contributes to the understanding of the diversity of cellular senescence in cancers and provides novel insight for tumor therapy.

Abstract Persister cells (PS) selected for anticancer therapy have been recognized as a significant contributor to the development of treatment‐resistant malignancies. It is found that imposing glutamine restriction induces the generation of PS, which paradoxically bestows heightened resistance to glutamine restriction treatment by activating the integrated stress response and initiating the general control nonderepressible 2‐activating transcription factor 4‐alanine, serine, cysteine‐preferring transporter 2 (GCN2‐ATF4‐ASCT2) axis. Central to this phenomenon is the stress‐induced ATF4 translational reprogramming. Unfortunately, directly targeting ATF4 protein has proven to be a formidable challenge because of its flat surface. Nonetheless, a G‐quadruplex structure located within the promoter region of ATF4 (ATF4‐G4) is uncovered and resolved, which functions as a transcriptional regulator and can be targeted by small molecules. The investigation identifies the natural compound coptisine (COP) as a potent binder that interacts with and stabilizes ATF4‐G4. For the first time, the high‐resolution structure of the COP‐ATF4‐G4 complex is determined. The formation of this stable complex disrupts the interaction between transcription factor AP‐2 alpha (TFAP2A) and ATF4‐G4, resulting in a substantial reduction in intracellular ATF4 levels and the eventual death of cancer cells. These seminal findings underscore the potential of targeting the ATF4‐G4 structure to yield significant therapeutic advantages within the realm of persister cancer cells induced by glutamine‐restricted therapy.

Abstract Objective This study aimed to explore the association between slow‐wave sleep and the progression of motor and nonmotor symptoms in patients with PD. Methods Data were collected from the Parkinson's Progression Markers Initiative study. Slow‐wave sleep, also known as deep non‐rapid eye movement (DNREM) sleep, was objectively assessed using the Verily Study Watch. Motor function was assessed using the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale Part III score, Hoehn and Yahr stage, freezing of gait, motor fluctuations, and dyskinesia severity. Comprehensive assessments were conducted on nonmotor symptoms, including depression, anxiety, global cognitive function, and autonomic dysfunction. Statistical analyses involved repeated‐measures analysis of variance and linear regression. Results A total of 102 patients with PD were included in the study, with a median follow‐up duration of 3.4 years. In the long DNREM sleep duration group (n = 55), better motor function (DNREM × time interaction: F(1,100) = 4.866, p = 0.030), less severe sexual dysfunction (p = 0.026), and improved activities of daily living (p = 0.033) were observed at the last follow‐up visit compared with the short DNREM sleep duration group (n = 47). Reduced DNREM sleep duration is a risk factor for motor progression (β = −0.251, p = 0.021; 95% confidence interval = −0.465 to −0.038). Interpretation The findings suggest an association between longer DNREM sleep duration and slower motor and nonmotor progression in patients with PD.

Lung cancer (LC) is one of the most common cancer worldwide. Tumor-associated macrophages (TAMs) are important component of the tumor microenvironment (TME) and are closely related to the stages of tumor occurrence, development, and metastasis. Macrophages are plastic and can differentiate into different phenotypes and functions under the influence of different signaling pathways in TME. The classically activated (M1-like) and alternatively activated (M2-like) represent the two polarization states of macrophages. M1 macrophages exhibit anti-tumor functions, while M2 macrophages are considered to support tumor cell survival and metastasis. Macrophage polarization involves complex signaling pathways, and blocking or regulating these signaling pathways to enhance macrophages’ anti-tumor effects has become a research hotspot in recent years. At the same time, there have been new discoveries regarding the modulation of TAMs towards an anti-tumor phenotype by synthetic and natural drug components. Nanotechnology can better achieve combination therapy and targeted delivery of drugs, maximizing the efficacy of the drugs while minimizing side effects. Up to now, nanomedicines targeting the delivery of various active substances for reprogramming TAMs have made significant progress. In this review, we primarily provided a comprehensive overview of the signaling crosstalk between TAMs and various cells in the LC microenvironment. Additionally, the latest advancements in novel drugs and nano-based drug delivery systems (NDDSs) that target macrophages were also reviewed. Finally, we discussed the prospects of macrophages as therapeutic targets and the barriers to clinical translation.

Abstract Backgrounds Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia. Maintaining a balance between the proliferation and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs) is crucial for preventing the erosion of bone and cartilage and, ultimately, mitigating the progression of RA. We found that the lncRNA LEF1-AS1 was expressed at low levels in the RASFs and inhibited their abnormal proliferation by targeting PIK3R2 protein and regulating the PI3K/AKT signal pathway through its interaction with miR-30-5p. In this study, we fabricated a nano-drug delivery system for LEF1-AS1 using Zn-Adenine nanoparticles (NPs) as a novel therapeutic strategy against RA. Methods The expression levels of LEF1-AS1, miR-30-5p, PIK3R2, p-PI3K, and p-AKT were detected in the primary RASFs and a human fibroblast-like synovial cell line (HFLS). Zn-Adenine nanoparticles (NPs) were functionalized with anti-CD305 antibody to construct (Zn-Adenine)@Ab. These NPs were then loaded with LEF1-AS1 to form (Zn-Adenine)@Ab@lncRNA LEF1-AS1. Finally, the (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs were locally injected into a rat model with collagen-induced arthritis (CIA). The arthritic injuries in each group were evaluated by HE staining and other methods. Results LEF1-AS1 was expressed at low levels in the primary RASFs. High expression levels of LEF1-AS1 were detected in the HFLS cells, which corresponded to a significant downregulation of miR-30-5p. In addition, the expression level of PIK3R2 was significantly increased, and that of p-PI3K and p-AKT were significantly downregulated in these cells. The (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly inhibited the proliferation of RASFs and decreased the production of inflammatory cytokines (IL-1β, IL-6, TNF-α). Intra-articular injection (IAI) of (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly alleviated cartilage destruction and joint injury in the CIA-modeled rats. Conclusions LEF1-AS1 interacts with miR-30-5p to inhibit the abnormal proliferation of RASFs by regulating the PI3K/AKT signal pathway. The (Zn-Adenine)@Ab NPs achieved targeted delivery of the loaded LEF1-AS1 into the RASFs, which improved the cellular internalization rate and therapeutic effects. Thus, LEF1-AS1 is a potential target for the treatment of RA.

In this work, the influences of La2O3 addition on the connectivity of the glass network, phase compositions and microstructural evolution of weld slag were investigated through Raman spectrum, X-ray powder diffraction (XRPD), SEM and EBSD technologies. All experimental results indicated that La2O3 addition could modify the whole glass network’s connectivity and short-ordered units. According to the Raman spectrum, only 1 wt.% La2O3 addition resulted in the occurrence of a unique linking mode of Si-O and Al-O tetrahedrons that was assigned to feldspar phases (albite or anorthite). Further XRPD examination showed that the primary phases were albite and anorthite, which agreed with the Raman results. Moreover, enhanced linkage between Si-O and Al-O tetrahedrons needs a large amount Na+ to achieve electric neutrality. This repaired the connectivity of the slag network due to the lack of Na+. Additionally, the solubility of La2O3 in the slag matrix was limited to about 3 wt.%. Adding further La2O3 to this weld slag, the existence form of La2O3 retained its original status. Thus, La2O3 addition that exceeded 3 wt.% had little effect on the slag connectivity besides providing a phase interface. In conclusion, La2O3 addition in weld slag could promote the hardness and the formation of feldspar phases. Feldspar is an extremely fragile silicon aluminate crystal. The factors mentioned above caused the detachability to be enhanced when adding La2O3.

Abstract Primary pulmonary sarcoma (PPS) is a rare and poor prognostic malignancy that results from current clinical studies are lacking. Our study aimed to investigate the prognostic factors of PPS and to construct a predictive nomogram that predict the overall survival (OS) rate. We extracted data on patients diagnosed with PPS from 2010 to 2019 in the SEER database. A total of 169 patients were included after screening by inclusion and exclusion criteria. Univariate and multivariate COX regression analyses showed that age, pathological grade, liver metastasis, surgical intervention, and chemotherapy influenced the prognosis. We constructed the prediction model nomogram based on these factors. Moreover, the results of the internal and external ROC curves, calibration curves, and DCA plots confirmed that the model has good discrimination, accuracy, and clinical practice efficacy. The present study is the first population-based study to explore the factors affecting the prognosis of PPS. We established a novel prognostic nomogram to predict the OS rate, which can help to make proper clinical decisions.

Abstract Background Lung Large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive, high‐grade neuroendocrine carcinoma with a poor prognosis, mainly seen in elderly men. To date, we have found no studies on predictive models for LCNEC. Methods We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database of confirmed LCNEC from 2010 to 2018. Univariate and multivariate Cox proportional risk regression analyses were used to identify independent risk factors, and then we constructed a novel nomogram and assessed the predictive effectiveness by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results A total of 2546 patients with LCNEC were included, excluding those diagnosed with autopsy or death certificate, tumor, lymph node, metastasis (TNM) stage, tumor grade deficiency, etc., and finally, a total of 743 cases were included in the study. After univariate and multivariate analyses, we concluded that the independent risk factors were N stage, intrapulmonary metastasis, bone metastasis, brain metastasis, and surgical intervention. The results of ROC curves, calibration curves, and DCA in the training and validation groups confirmed that the nomogram could accurately predict the prognosis. Conclusions The nomogram obtained from our study is expected to be a useful tool for personalized prognostic prediction of LCNEC patients, which may help in clinical decision‐making.

Abstract Although 2D material van der Waals heterostructures (vdWHs) exhibit many novel properties and applications, 2D homojunctions have unique advantages in interface lattice matching, band continuity, and charge transfer efficiency. However, the rectification performances of 2D homojunction diodes are severely limited by the small junction barrier, mainly due to inefficient charge doping. In this work, an ultrahigh‐rectification‐ratio WSe2 homojunction diode achieved by the semi‐floating gate doping of graphdiyne oxide (GDYO) is reported. Utilizing the WSe2/GDYO direct charge trapping mode can free the inhibition of charge capturing efficiency by removing conventional insulating barriers and thus improve the rectification ratio. The C─C(sp) and oxygen‐containing functional groups in the GDYO layer can provide outstanding charge‐trapping ability due to their unsaturation. Furthermore, the oxygen plasma treatment used for oxidizing graphdiyne (GDY) into GDYO can make GDYO a flatter surface, thus creating strong‐coupling WSe2/GDYO interfaces to improve the charge transfer efficiency and enhance the electrostatic doping effect. Besides, the WSe2/GDYO interfaces are confirmed to possess a higher junction barrier than that of the WSe2/GDY interfaces. This research proposes a brand‐new approach to building p–n junctions via charge trapping and the homojunction diode with a record‐highest rectification ratio of up to 106 is obtained.

Introduction: Luteolin is a plant-derived flavonoid that exhibits a broad range of pharmacological activities. Studies on luteolin have mainly focused on its use for hyperlipidaemia prevention, whereas the capacity of the flavonoid to hinder hyperglycaemia development remains underexplored. Objectives: To probe the anti-hyperglycemic mechanism of 6,8-guanidyl luteolin quinone-chromium coordination (GLQ.Cr), and to assess its regulatory effect on intestinal microbiota in type 2 diabetes mellitus (T2DM) mice. Methods: High-sucrose/high-fat diet-induced and intraperitoneal injection of streptozotocin was used to develop a T2DM model. Glycometabolism related indicators, histopathology, and gut microbiota composition in caecum samples were evaluated, and RNA sequencing (RNA-seq) of liver samples was conducted. Faecal microbiota transplantation (FMT) was further used to verify the anti-hyperglycemic activity of intestinal microbiota. Results: The administration of GLQ.Cr alleviated hyperglycaemia symptoms by improving liver and pancreatic functions and modulating gut microbe communities (Lactobacillus, Alistipes, Parabacteroides, Lachnoclostridium, and Desulfovibrio). RNA-seq analysis showed that GLQ.Cr mainly affected the peroxisome proliferative activated receptor (PPAR) signalling pathway in order to regulate abnormal glucose metabolism. FMT significantly modulated the abundance of Lactobacillus, Alloprevotella, Alistipes, Bacteroides, Ruminiclostridium, Brevundimonas and Pseudomonas in the caecum to balance blood glucose levels and counteract T2DM mice inflammation. Conclusion: GLQ.Cr improved the abnormal glucose metabolism in T2DM mice by regulating the PPAR signalling pathway and modulating intestinal microbial composition. FMT can improve the intestinal microecology of the recipient and in turn ameliorate the symptoms of T2DM-induced hyperglycaemia.

Objective Lumbar sympathetic trunk (LST) injury is one of the major complications after oblique lumbar interbody fusion (OLIF). LST injury often manifests as unequal skin temperature in lower limbs after operation, and there may be a large number of missed diagnoses due to the lack of attention and different diagnostic methods. The study aimed to investigate the incidence and clinical characteristics of LST injury after OLIF. Methods The data of patients with lumbar degenerative diseases who underwent OLIF in our hospital from April 2016 to October 2017 were retrospectively analyzed. Finally, a total of 54 patients were included. There were 10 males and 44 females, aged 58.4 ± 10.9 years. The skin temperature of lower limbs was measured before and a day after surgery. The patients were followed up at 1 week, 6 weeks, 6 months, and 2 years after the surgery. Likert five‐point scale was used to evaluate the discomfort caused by LST injury. Injury severity score was introduced to grade injury degree according to the recovery time of postoperative symptoms. The chi‐square test was used to analyze the association of incidence of lumbar sympathetic trunk (LST) injury with contributing factors, such as gender and number of surgical segments. Results The unequal temperature was not found before surgery in all the patients. Postoperatively, 16 cases (29.6%) had difference of skin temperature more than 0.5 °C and were diagnosed with LST injury. Eight patients (14.8%) had self‐perception of skin temperature differences, and 12 patients (22.2%) had other symptoms, such as muscle pain, numbness, and weakness, which were not statistically different between patients with and without lumbar sympathetic trunk injury (p > 0.05). In the 16 patients with LST injury, the difference of skin temperature between the two legs was 0.6 ± 0.1 °C on the first day, and the temperature difference lasted for 1.5–~12 months. According to Likert five‐point scale, two cases (12.5%) were poor, and 14 cases (87.5%) were moderate immediately after surgery. Fifteen cases improved to some extent 6 weeks to 12 months after surgery. Conclusion Postoperative LST injury is mainly manifested by different temperature of lower limbs. The incidence was higher in patients with multi‐segment OLIF than in those with single‐segment OLIF, and the subjective experience of most patients with LST injury was moderate discomfort.

Abstract Background The increasing incidence of osteoporosis in recent years has aroused widespread public concern; however, existing effective treatments are limited. Therefore, new osteoporosis treatment methods, including stem cell transplantation and exosome therapy, have been proposed and are gaining momentum. Exosomes are considered to have greater potential for clinical application owing to their immunocompatibility. This study summarises the latest evidence demonstrating the efficacy of exosomes in improving bone loss in the treatment of osteoporosis. Main text This systematic review and meta-analyses searched PubMed, Embase, and Cochrane Library databases from inception to 26 March 2022 for osteoporosis treatment studies using stem cell-derived exosomes. Six endpoints were selected to determine efficacy: bone mineral density, trabecular bone volume/tissue volume fraction, trabecular number, trabecular separation, trabecular thickness, and cortical thickness. The search generated 366 citations. Eventually, 11 articles that included 15 controlled preclinical trials and 242 experimental animals (rats and mice) were included in the meta-analysis. Conclusion The results were relatively robust and reliable despite some publication biases, suggesting that exosome treatment increased bone mass, improved bone microarchitecture, and enhanced bone strength compared with placebo treatments. Moreover, stem cell-derived exosomes may favour anabolism over catabolism, shifting the dynamic balance towards bone regeneration.

Alternative splicing crucially affects various biological processes, however, its function in heart development is largely unknown. Here, the authors show an essential role of alternative splicing factor PTBP1 in ventricular chamber development.

Abstract Purpose Retinol-binding protein 4 (RBP4) has been considered to be related to metabolic related diseases, such as hyperuricemia, obesity, and diabetes mellitus. However, whether nonalcoholic fatty liver disease (NAFLD) is related to RBP4 is unclear. Previous studies on the relationship between NAFLD and RBP4 levels have yielded inconsistent results. Hence, this meta-analysis was aimed to clarify whether circulating RBP4 levels are in relation to the risk of NAFLD. Methods A meta-analysis was performed by applying observational studies to evaluate circulating RBP4 levels and NAFLD. Eligible studies published up to September 23, 2022, were searched in Embase, PubMed, and Cochrane databases. Results In this study, 17 cross-sectional studies involving 8423 participants were included. Results from a random effects model showed that circulating RBP4 levels were higher in NAFLD patients than non-NAFLD (standardized mean difference (SMD) 0.28; 95% confidence intervals (CI): 0.11–0.46, I2: 89.8%). This association was confirmed in the Yellow race. However, no significant association was noted in the Caucasian race. After excluding the morbidly obese Population from the weight loss study (n = 2), the results of the comparison remained largely unchanged (SMD 0.28; 95% CI: 0.10–0.47, I2: 90.8%). Remarkable publication bias was not found. Although considerable heterogeneity was observed among the studies, no potential sources of heterogeneity were found in the subgroup analysis. Diagnostic methods for NAFLD were determined to be a potential source of statistical heterogeneity in meta-regression. Conclusion The findings provide evidence that NAFLD patients exhibit higher levels of circulating RBP4 compared with controls, but high heterogeneity was observed. Thus, a high RBP4 level is probably a potential risk factor for NAFLD. To confirm the causal link between NAFLD and RBP4 level of causality, further prospective cohort studies are needed.

Summary: Major histocompatibility complex (MHC) class II-reactive CD8+ T cells are found in humans and animals, but little is known about their identity, development, and function. In this study, we discover a group of CD8+ T cells reactive to both MHC class I and II molecules in MHC class II-deficient mice. We clone their T cell receptors (TCRs) and analyze their development and function. In wild-type animals, thymocytes bearing those TCRs are purged by negative selection. In the absence of MHC class II, they develop into mature CD8+ T cells. When encountering MHC class II in the periphery, they undergo robust activation and proliferation, attack self-tissues, and cause lethal autoimmune diseases. In adoptive T cell therapy, those CD8+ T cells are able to efficiently control MHC class II-expressing tumors. This study opens the door to investigation of dual-reactive CD8+ T cells, their development and selection in the thymus, and the perils and promises when their normal development and selection are compromised.

Lung cancer (LC) is one of the leading causes of high cancer-associated mortality worldwide. Non-small cell lung cancer (NSCLC) is the most common type of LC. The mechanisms of NSCLC evolution involve the alterations of multiple complex signaling pathways. Even with advances in biological understanding, early diagnosis, therapy, and mechanisms of drug resistance, many dilemmas still need to face in NSCLC treatments. However, many efforts have been made to explore the pathological changes of tumor cells based on specific molecular signals for drug therapy and targeted delivery. Nano-delivery has great potential in the diagnosis and treatment of tumors. In recent years, many studies have focused on different combinations of drugs and nanoparticles (NPs) to constitute nano-based drug delivery systems (NDDS), which deliver drugs regulating specific molecular signaling pathways in tumor cells, and most of them have positive implications. This review summarized the recent advances of therapeutic targets discovered in signaling pathways in NSCLC as well as the related NDDS, and presented the future prospects and challenges.