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Abstract The anomalous photovoltaic effect (APE) in polar crystals is a promising avenue for overcoming the energy conversion efficiency limits of conventional photoelectric devices utilizing p-n junction architectures. To facilitate effective photocarrier separation and enhance the APE, polar materials need to be thinned down to maximize the depolarization field. Here, we demonstrate Janus MoSSe monolayers (~0.67 nm thick) with strong spontaneous photocurrent generation. A photoresponsivity up to 3 mA/W, with ~ 1% external quantum efficiency and ultrafast photoresponse (~50 ps) were observed in the MoSSe device. Moreover, unlike conventional 2D materials that require careful twist alignment, the photovoltage can be further scaled up by simply stacking the MoSSe layers without the need for specific control on interlayer twist angles. Our work paves the way for the development of high-performance, flexible, and compact photovoltaics and optoelectronics with atomically engineered Janus polar materials.

Abstract The current bolt detection for overhead work robots used for transmission lines faces the problems of lightweight algorithms and high accuracy of target detection. To address these challenges, this paper proposes a lightweight bolt detection algorithm based on improved YOLOv8 (you only look once v8) model. Firstly, the C2f module in the feature extraction network is integrated with the self‐calibrated convolution module, and the model is streamlined by reducing spatial and channel redundancies of the network through the SRU and CUR mechanisms in the module. Secondly, the P2 small object detection layer is introduced into the neck structure and the BiFPN network structure is incorporated to enhance the bidirectional connection paths, thereby promoting the upward and downward propagation of features. It improves the accuracy of the network for bolt‐small target detection. The experimental results show that, compared to the original YOLOv8 model, the proposed algorithm demonstrates superior performance on a self‐collected dataset. The mAP accuracy is improved in this paper by 9.9%, while the number of model parameters and the model size is reduced by 0.973 × 106 and 1.7 MB, respectively. The improved algorithm improves the accuracy of the bolt detection while reducing the computation complexity to achieve more lightweight model.

Abstract Genetic transformation is a pivotal approach in plant genetic engineering. Peanut (Arachis hypogaea L.) is an important oil and cash crop, but the stable genetic transformation of peanut is still difficult and inefficient. Recently, the pollen tube injection pathway has been shown to be effective for the genetic transformation of peanut. However, the poor reproducibility of this pathway is still controversial. In this study, the appropriate time and location of injection, along with transgenic screening, were systematically investigated in the pollen tube mediated peanut genetic transformation. Our findings revealed that Agrobacterium injections could be conducted within a time window of two to three hours preceding and succeeding the blooming process. Among the various selective markers evaluated, the Basta screening emerged as the most expedient, followed closely by the DsRed visual screening. According to resistance screening and molecular identification, the average transformation efficiency was 2.6% in the heritable transgenic progenies, which was more likely affected by individual operation by style cavity injection. Furthermore, the use of synergistic FT artificially regulated the blooming of peanuts under indoor conditions, facilitating operations involving keel petal injection and ultimately enhancing the genetic transformation efficiency. Thus, our study systematically validated the feasibility of peanut genetic transformation through an optimized pollen-tube injection technique without tissue culture, potentially guiding future advancements in peanut engineering and molecular breeding programs.

Abstract Background Recent studies have highlighted the distinct ratio of PD-1 + Treg/PD-1 + CD8 for prognosis prediction. However, it remains unclear about the association of this ratio and tertiary lymphoid structures (TLS) with prognosis and response to neoadjuvant or conversion therapy in advanced gastric cancer. Methods Firstly, fresh postoperative samples from 68 gastric cancer patients in Renji Hospital were collected. Meanwhile, immune cell infiltration as well as clinical prognosis analysis were conducted. Subsequently, we further systematically evaluated flow cytometry analysis of tumor samples and TLS expression in 38 gastric cancer patients with different response situations after neoadjuvant therapy. Also, a Renji conversion therapy cohort including 10 patients with complete matching samples before and after treatment was established to receive RNA sequencing analysis and multiplex immunohistochemistry (mIHC) tests. The corresponding TLS score and immune cell infiltration were further compared based on therapeutic response variations. Results In general, the ratio of PD-1 + Treg/PD-1 + CD8>1 could be regarded as an independent predictor of prognosis in advanced gastric cancer patients. Moreover, PD-1 + Treg/PD-1 + CD8

Abstract Abundant infiltration of tumor-associated macrophages (TAMs) within the tumor stroma plays a pivotal role in inducing immune escape in pancreatic cancer (PC). Lactate serves as a direct regulator of macrophage polarization and functions, although the precise regulation mechanism remains inadequately understood. Our study revealed that PC cells (PCs) promote macrophage polarization toward M2d through high lactate secretion. M2d is characterized by elevated secretion of IL-10 and VEGF-A, which diminish CD8+T cells cytotoxicity and promote tumor neoangiogenesis simultaneously. Additionally, we identify 2,5’-oligoadenylate synthase 3 (OAS3) as an essential regulator of M2d polarization, upregulated by PCs via lactate/METTL3/OAS3 axis. Increased OAS3 expression in TAMs correlates with m6A modification mediated by METTL3 on OAS3 mRNA and is associated with poorer prognosis in PC patients. OAS3 deficiency in macrophages substantially impairs IL-10highVEGF-AhighM2d polarization and their pro-tumor functions while enhancing the therapeutic efficacy of gemcitabine and anti-PD-L1 mAb in humanized mouse models. In conclusion, OAS3 presents as a promising immune therapeutic target for reversing IL-10highVEGF-AhighM2d infiltration and restoring CD8+T cell-mediated anti-tumor immunity in pancreatic cancer. Graphical abstract

This paper proposes a digital review method based on BIM (Building Information Modeling). The C# language is used to structure and compile architectural design standards into computer identifiable discriminant conditions, match and judge BIM model information, and return the review results. Encapsulate the digital review system’s core code into an executable program by Microsoft’s NET framework. The program includes Login, Model Review, Result Display, and Result Export functions. As a case study, the paper uses the fire control review of construction drawings for a newly constructed student dormitory to implement the process of a digital drawing examination system. The results show that compared with the traditional manual review, the digital review reduces the cost of high-quality human resources, simplifies the workflow of construction drawing review, and shortens the drawing review cycle. It plays an active role in promoting the whole process of digital achievement delivery and application of construction engineering.

This study aims to conduct a cost-effectiveness analysis of three different anesthesia strategies, namely chatting while under local anesthesia (Chat-LA), total intravenous anesthesia (TIVA), and general anesthesia with laryngeal mask airway (GA-LMA), employed in transperineal magnetic resonance imaging (MRI)/ultrasound (US) fusion prostate biopsy (TP-MUF-PB). A retrospective study was conducted involving 1202 patients who underwent TP-MUF-PB from June 2016 to April 2023 at The First Affiliated Hospital of Soochow University (Suzhou, China). Clinical data and outcomes, including total costs, complications, and quality-adjusted life years (QALYs), were compared. Probability sensitivity and subgroup analyses were also performed. Chat-LA was found to be the most cost-effective option, outperforming both TIVA and GA-LMA. However, subgroup analyses revealed that in younger patients (under 65 years old) and those with smaller prostate volumes (

Background and objective: Few studies on endoscopic management of primary obstructive megaureter (POM) in adult patients have been reported. Our objective was to describe our technique and long-term outcomes for endoscopic management of adult POM. Methods: We included 76 adult POM patients undergoing endoscopic management between September 2015 and January 2024. Under endoscopic control, the stricture was dilated to 24–30 Fr while maintaining a balloon pressure of 25–35 atm for 3 min. An additional incision of the stenotic ring using either an electrode or holmium laser was performed in 39 patients. Data for patient characteristics, intraoperative variables, surgical complications, and follow-up results were analyzed. A descriptive statistical analysis was performed. Surgical success was defined as no tubes or stents in the body, stable or improved symptoms and renal function, and the absence of reflux or obstruction during the follow-up period. Key findings and limitations: All procedures were completed without conversion to open or laparoscopic surgery. The median operative time was 45 min (range 16–165) with median estimated blood loss of 2 ml (range 0–150). The median postoperative hospital stay was 3 d (range 1–15). No intraoperative complication occurred. At median postoperative follow-up of 42 mo (range 3–100) the overall success rate was 92.1%. Restenosis of the vesicoureteral junction (Clavien-Dindo grade III) occurred in five patients (6.6%), and high-grade vesicoureteral reflux occurred in one patient (1.3%), all of whom required secondary reconstruction surgery. Conclusions and clinical implications: The results indicate that our endoscopic management for adult POM is safe and effective, with favorable long-term outcomes. This approach could potentially serve as a first-line treatment option for adult POM. Patient summary: Primary obstructive megaureter (POM) occurs when the flow of urine is blocked because of a narrow segment in the tube between the kidney and bladder (ureter), which causes widening of the ureter further up. For our minimally invasive technique, a telescope is inserted through the urethra and bladder to reach the ureter for surgical treatment. Our results show that this is a safe procedure for POM in adults.

Compared with a single unmanned surface vessel (USV), multiple USVs have the advantages of strong maneuverability, high reliability, and low cost. Multiple USVs have potential oceanic transportation, resource exploration, and maritime rescue applications. However, cooperative formation control of multiple USVs is a significant yet challenging problem. The main difficulties arise from the limited communication and the existence of model uncertainties and external perturbations. Therefore, this paper proposes a fixed-time adaptive distributed control strategy consisting of a fixed-time distributed observer and local controller for cooperative formation control of multiple USVs under local communication in complex marine environment. First, a fixed-time distributed observer is constructed for each follower USV to estimate the virtual leader’s position and velocity in fixed time by considering that only a portion of follower USVs can directly access the state information from the virtual leader. Based on the estimated information, a fixed-time local controller is designed for each follower USV to track the desired trajectory generated by the virtual leader in a fixed time using the backstepping method. In particular, in the local controller design process, a parameter adaptive mechanism is introduced to estimate the square of the upper bound of the lumped disturbance term, including model uncertainty and external disturbance to compensate for them. Thus, the proposed controller is smooth to guarantee the control accuracy, and the chattering phenomenon can be avoided simultaneously. Stability analysis of the proposed fixed-time observer and local controller is also presented. Mathematical proofs show that the proposed observer and controller can ensure that each USV can complete the position estimation and virtual leader velocity in a fixed time, thereby making the tracking error converge to the zero neighborhood in a fixed time. Finally, USVs with the proposed control strategy can follow the virtual leader and maintain the formation as shown in the simulation. Additionally, a comparative simulation is designed, where the control performance of the proposed strategy is compared with that of the commonly used PD controller under the same condition. The simulation results show that the proposed controller has superior control accuracy and convergence rate in controlling the USVs to track the desired position and velocity of the demanded formation. Moreover, the chattering phenomenon of the control inputs is significantly suppressed.

Abstract Chronic heart failure (CHF) can induce chronic kidney disease (CKD), called type 2 cardio-renal syndrome (CRS2). The mechanism is not completely clear, and there is a lack of early warning biomarkers of CKD in the context of CHF. Two CKD, one CHF-PBMC and four CHF-cardiac tissue expression profile datasets were obtained from GEO database. Differential expression analysis and WGCNA were used to detect CKD key genes and CHF-related secreted proteins. Protein–protein interaction (PPI), functional enrichment, and cMAP analysis reveal potential mechanisms and drugs of CHF-related CKD. Five machine learning algorithms were used to screen candidate biomarkers, construct a diagnostic nomogram for CKD and validate it in two external cohorts. Clinical serum samples were collected in our hospital to evaluate the correlation and diagnostic value of biomarkers and CKD. 225 CKD key genes and 316 CHF-related secreted proteins were identified. Four key subgroups, including 204 genes, were identified as CRS2-related pathogenic genes by PPI analysis. Enrichment analysis revealed that the identified subgroups exhibited significant enrichment in cytokine action, immune responses, and inflammatory processes. The cMAP analysis highlighted metiradone as a drug with greater potential for therapeutic intervention for CRS2. Utilizing five machine learning algorithms, three hub genes (CD48, COL3A1, LOXL1) were pinpointed as potential biomarkers for CKD, and a nomogram model was constructed. Receiver operating characteristic analysis demonstrated that the nomogram’s area under the curve (AUC) exceeded 0.80 in both the CKD combined dataset and two external cohorts. In addition, the three biomarkers were significantly correlated with the glomerular filtration rate, and the AUC of the model predicting disease progression was 0.944. Furthermore, analysis of immune cell infiltration indicated a correlation between the three biomarkers and the infiltration fraction of macrophages, neutrophils, and other immune cells in CKD. Our clinical cohort validated the expression patterns of three biomarkers in serum, and the diagnostic model achieved an AUC of 0.876. CHF has the potential to facilitate the progression of CKD via the release of cardiac and PBMC secreted proteins. Furthermore, CD48, COL3A1, and LOXL1 have been identified as potential biomarkers for the detection of CKD.

Abstract Aims To investigate the fundus characteristics and macular optical coherence tomography angiography (OCTA) metrics in patients with myelinated retinal nerve fibers (MRNF) and to identify the associations among myopic parameters, fundus metrics, and OCTA metrics. Methods The single-center case-control study included 15 patients with monocular MRNF and 15 patients without MRNF, matched for age, affected eyes’ spherical equivalent error (SER), and axial length (AL) between May 2021 and December 2021. Fundus features, including the entire MRNF area (Area1), the denser MRNF area (Area2), and the shortest distance from the fovea to the MRNF border (Df−m), along with ocular parameters, including SER, AL, best corrected visual acuity (BCVA), and OCTA metrics at the fovea, including choroidal (ChT) and retinal (ReT) thicknesses at the fovea, the foveal avascular zone area (FAZ), foveal avascular zone perimeter (FAZP), FAZ-circularity index (FAZ-CI), and foveal vessel density in a 300-µm wide region (FD-300), were assessed. Results The SER, AL, and BCVA were significantly different, and the ChT was thinner in the affected eyes than in the contralateral eyes. Compared with matched eyes, affected eyes had reduced BCVA and thinner ReT. In the affected eyes, both Area1 and Area2 were negatively correlated with SER (r 1 = -0.84, r 2 = -0.65), △SER (r 1 = -0.86, r 2 = -0.61), ReT at the vertical superior 3 mm (VS) (r 1 = -0.78, r 2 = -0.67), and ChT_VS (r 1 = -0.64, r 2 = -0.62), and positively correlated with AL (r 1 = 0.82, r 2 = 0.52) and BCVA (r 1 = 0.54, r 2 = 0.59). Df−m was negatively correlated with BCVA (r = -0.57). Conclusion The presence of MRNF affects BCVA and ReT at the fovea. The area of the MRNF, as well as the distance from the MRNF to the fovea, are closely associated with the affected eyes’ BCVA, SER, AL, and the degree of anisometropia.

Abstract Background Breast cancer (BC) is the most common malignant tumor in women worldwide, and further elucidation of the molecular mechanisms involved in BC pathogenesis is essential to improve the prognosis of BC patients. RNA Binding Motif Protein 8 A (RBM8A), with high affinity to a myriad of RNA transcripts, has been shown to play a crucial role in genesis and progression of multiple cancers. We attempted to explore its functional significance and molecular mechanisms in BC. Methods Bioinformatics analysis was performed on publicly available BC datasets. qRT-PCR was used to determine the expression of RBM8A in BC tissues. MTT assay, clone formation assay and flow cytometry were employed to examine BC cell proliferation and apoptosis in vitro. RNA immunoprecipitation (RIP) and RIP-seq were used to investigate the binding of RBM8A/EIF4A3 to the mRNA of IGF1R/IRS-2. RBM8A and EIF4A3 interactions were determined by co-immunoprecipitation (Co-IP) and immunofluorescence. Chromatin immunoprecipitation (Ch-IP) and dual-luciferase reporter assay were carried out to investigate the transcriptional regulation of RBM8A by TEAD4. Xenograft model was used to explore the effects of RBM8A and TEAD4 on BC cell growth in vivo. Results In this study, we showed that RBM8A is abnormally highly expressed in BC and knockdown of RBM8A inhibits BC cell proliferation and induces apoptosis in vitro. EIF4A3, which phenocopy RBM8A in BC, forms a complex with RBM8A in BC. Moreover, EIF4A3 and RBM8A complex regulate the expression of IGF1R and IRS-2 to activate the PI3K/AKT signaling pathway, thereby promoting BC progression. In addition, we identified TEAD4 as a transcriptional activator of RBM8A by Ch-IP, dual luciferase reporter gene and a series of functional rescue assays. Furthermore, we demonstrated the in vivo pro-carcinogenic effects of TEAD4 and RBM8A by xenograft tumor experiments in nude mice. Conclusion Collectively, these findings suggest that TEAD4 novel transcriptional target RBM8A interacts with EIF4A3 to increase IGF1R and IRS-2 expression and activate PI3K/AKT signaling pathway, thereby further promoting the malignant phenotype of BC cells.

Abstract Observational and genetic studies have reported the relationship between dyslexia and Alzheimer’s disease (AD). Until now, the causal effect of dyslexia on AD risk has remained unclear. We conducted a two-sample univariable Mendelian randomization (MR) analysis to determine the causal association between dyslexia and the risk of AD, vascular dementia (VD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) and its four subtypes. First, we selected 42 dyslexia genetic variants from a large-scale genome-wide association studies (GWAS) dataset and extracted their corresponding GWAS summary statistics from AD, VD, LBD, and FTD. Second, we selected four MR methods, including inverse-variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO. Heterogeneity, horizontal pleiotropy, and leave-one-out sensitivity analysis were then used to evaluate the reliability of all causal estimates. We also conducted multivariable MR (MVMR) and mediation analysis to assess the potential mediating role of cognitive performance (CP) or educational achievement (EA) on the causal association between dyslexia and AD. Two MVMR methods, including MV IVW and MV-Egger, and two-step MR were used to perform the analysis. Using IVW, we found a significant causal association between increased dyslexia and increased risk of AD (OR = 1.15, 95% CI: 1.04–1.28, P = 0.006), but not VD, LBD, FTD, or its four subtypes. MR-PRESSO further supported the statistically significant association between dyslexia and AD (OR = 1.15, 95% CI: 1.05–1.27, P = 0.006). All sensitivity analyses confirmed the reliability of causal estimates. Using MV IVW and mediation analysis, we found no causal relationship between dyslexia and AD after adjusting for CP but not EA, CP mediated the total effect of dyslexia on AD with a proportion of 46.32%. We provide genetic evidence to support a causal effect of increased dyslexia on increased risk of AD, which was largely mediated by CP. Reading activity may be a potential intervention strategy for AD by improving cognitive function.

Background and aimsMultiplex immunohistochemistry/immunofluorescence (mIHC/IF), which uses the tyramide signal amplification (TSA) technique, enables sequential staining of multiple targets in formalin-fixed paraffin-embedded (FFPE) samples without worrying about cross-reactivity. This approach has received considerable attention from researchers over the past decades. This article aims to provide a bibliometric analysis of the research progress and perspectives on the application of TSA-based mIHC/IF.MethodsWe collected all the TSA-based mIHC/IF documents published between 2007 and 2023 from the Web of Science Core Collection (WoSCC) database. CiteSpace, VOSviewer and Bibliometrix R Package were used to perform the bibliometrics analysis, including details about annual publications, countries, institutions, authors, journals, and research topics and hotspots.ResultsA total of 873 relevant publications (811 articles and 62 reviews) with a time span of 17 years (2007-2023) were obtained. The number of annual publications started to increase rapidly since 2016. The United States (307, 35.17%) and the People’s Republic of China (297, 34.02%) are the top two listed countries for both the number of articles produced and the citations. The University of Texas System (53, 6.07%) was the most productive institution. Integrating these results of hotspot and frontier analysis, TSA-based mIHC/IF provides significant benefits, particularly in neurology, cancer and immunology.ConclusionThis study conducted a comprehensive bibliometric analysis for the use of TSA-based mIHC/IF. As TSA-based mIHC/IF and its associated imaging systems and analytic software progress, it will become the most promising tool for describing the variety of the whole tissue for a better understanding of pathological or physiological behavior.

Perinatal depression (PD) is a highly prevalent psychological disorder that has a detrimental effect on infant and maternal physical and mental health, but effective and objective assessment of PD is still insufficient. In recent years, the functional near-infrared spectroscopy (fNIRS) has been acknowledged as an effective non-invasive tool for clinical assessment of depression. This study proposed a free association semantic task (FAST) paradigm for fNIRS-based assessment of PD. To better address the emotion characteristics of PD, the participants are required to generate a dynamic concept chain based on positive, negative or neutral seed words, while 48-channel fNIRS recordings over frontal and bilateral temporal regions. Results from twenty-two late-pregnant women revealed that, the oxyhemoglobin (oxy-Hb) changes during the FAST with the positive and negative seed words over the frontal region were correlated with PD severity, which was different from the correlation patterns in the FAST with neutral seed word and the classical verbal fluency test (VFT). Furthermore, distinct correlation patterns were also observed in the FAST with the positive and negative seed words, manifested in fNIRS channels corresponding to the right dorsolateral prefrontal cortex (DLPFC) and right inferior frontal gyrus (IFG), respectively. Moreover, regression analyses showed that the FAST with positive and negative seed words can well explain the severity of PD. Our findings suggest the proposed FAST paradigm as a promising approach for PD assessment.

Objective Mobilization and collection of peripheral blood stem cells (PBSCs) are time-intensive and costly. Excessive apheresis sessions can cause physical discomfort for donors and increase the costs associated with collection. Therefore, it is essential to identify key predictive factors for successful harvests to minimize the need for multiple apheresis procedures. Methods We retrospectively analyzed 88 PBSC donations at our hospital. Mobilization involved disease-specific chemotherapy plus human recombinant granulocyte-colony-stimulating factor (G-CSF; lenograstim) or G-CSF alone for 5 days, followed by apheresis on day 5. The baseline characteristics of donors, pre-apheresis complete blood counts, and CD34+ cells were evaluated. Univariate logistic regression, the eXtreme Gradient Boosting algorithm, and multivariate logistic regression were applied to select significant predictive variables. The multivariate logistic regression results were integrated into various machine learning models to assess predictive accuracy. Results The percentage of pre-collection monocytes (Mono%), age, and CD34+ cell percentage (CD34+ cell%) were identified as significant independent factors that could accurately predict the success of an initial PBSC harvest. Conclusions We used machine learning methods to identify and validate Mono%, age, and CD34+ cell% as significant factors predictive of successful PBSC harvest on the first attempt, offering important insight to guide the clinical harvesting of PBSCs.

AimsFew personalized monitoring models for valproic acid (VPA) in pediatric epilepsy patients (PEPs) incorporate machine learning (ML) algorithms. This study aimed to develop an ensemble ML model for VPA monitoring to enhance clinical precision of VPA usage.MethodsA dataset comprising 366 VPA trough concentrations from 252 PEPs, along with 19 covariates and the target variable (VPA trough concentration), was refined by Spearman correlation and multicollinearity testing (366 × 11). The dataset was split into a training set (292) and testing set (74) at a ratio of 8:2. An ensemble model was formulated by Gradient Boosting Regression Trees (GBRT), Random Forest Regression (RFR), and Support Vector Regression (SVR), and assessed by SHapley Additive exPlanations (SHAP) analysis for covariate importance. The model was optimized for R2, relative accuracy, and absolute accuracy, and validated against two independent external datasets (32 in-hospital and 28 out-of-hospital dataset).ResultsUsing the R2 weight ratio of GBRT, RFR and SVR optimized at 5:2:3, the ensemble model demonstrated superior performance in terms of relative accuracy (87.8%), absolute accuracy (78.4%), and R2 (0.50), while also exhibiting a lower Mean Absolute Error (9.87) and Root Mean Squared Error (12.24), as validated by the external datasets. Platelet count (PLT) and VPA daily dose were identified as pivotal covariates.ConclusionThe proposed ensemble model effectively monitors VPA trough concentrations in PEPs. By integrating covariates across various ML algorithms, it delivers results closely aligned with clinical practice, offering substantial clinical value for the guided use of VPA.

Objectives: Diabetes was associated with increased serum urate levels and a higher risk of dementia. However, current evidence regarding the association between serum urate and dementia is controversial.The research gap on how to effectively control urate levels in the population with diabetes still remains. We aim to examine the association of diabetes status and serum urate with dementia incidence, and the differences in this association among participants with different diabetes statuses. Methods: A total of 321,896 participants was recruited from the UK Biobank and followed up until 2022. Diabetes status was classified into diabetes, prediabetes and normoglycaemia according to the American Diabetes Association 2023 guideline. Serum urate levels were stratified using gender-specific quartiles of concentrations. All-cause dementia, Alzheimer’s disease and vascular dementia were ascertained using the International Classification of Diseases-10th revision (ICD-10). Cox proportional hazards regression models were used to examine the association between serum urate, diabetes status, and dementia incidence. Results: Of the 321,896 participants (mean age, 57 years old; 43.5% males), 7,087 (2.20%) individuals were diagnosed with dementia during the follow-up period. Diabetes was associated with a 70% 58%, and 134% increased risk for all-cause dementia, Alzheimer’s disease, and vascular dementia respectively. Elevated serum urate levels were associated with a lower risk of all-cause and cause-specific dementia regardless of the status of diabetes. Each standard deviation increase in urate concentration was related to a 11% reduced risk for all-cause dementia (HR, 0.89; 95% CI, 0.86 to 0.91), 7% for Alzheimer’s disease (HR, 0.93; 95% CI, 0.88 to 0.98), and 12% for vascular dementia (HR, 0.88; 95% CI, 0.81 to 0.95). Conclusion: : Appropriately higher urate levels within the threshold of hyperuricemia can reduce the adverse health effects of excessively high urate levels and better protect the cognitive health of people with varying diabetes status.

In recent decades, there has been a growing concern about the excessive consumption on petroleum-based sources. Scientists are now focused on increasing the utilization of natural and renewable sources instead of nonrenewable ones to produce safety and environmentally friendly products. Their aim is to maintain and enhance product performance while also keeping production costs in check. Within this framework, natural-fiber insulation boards emerge as a trending topic and consequently, also the use of natural adhesives to supply them and reach an entirely friendly-environment product. Natural-fiber insulation material performance is typically evaluated by its mechanical and physical properties. Among them are bending, compression, tensile strength, density, water absorption, and thermal conductivity. Throughout the cited literature, a diversity of vegetal-origin fibers, especially wood-fibers and natural adhesive sources like lignin, tannins, and proteins for insulation materials has been found, which are constantly improved in order to reach a superior production scale. This work provides a summary of research that focuses on natural fiber insulation products as well as natural adhesives, pointing to Polylactic Acid (PLA).

The potential function and mechanism of circRNAs in regulating malignant performances of Osteosarcoma (OS) cells have not been well investigated. The expression level of CircLMO7, miR-21-5p and ARHGAP24 were detected by RT-qPCR. The relationship between miR-21-5p and circ-LMO7, as well as between miR-21-5p and ARHGAP24, was predicted and examined through bioinformatics analysis and luciferase reporter gene experiments. Moreover, OS cell growth, invasion, migration, and apoptosis were detected using the cell counting kit-8 (CCK-8), transwell and flow cytometry assays, respectively. ARHGAP24 protein level was measured using western blotting. In present study, we choose to investigate the role and mechanism of circ-LOM7 on OS cell proliferation, migration and invasion. circ-LOM7 was found to be down-regulated in OS tissues and cell lines. Enforced expression of circ-LOM7 suppressed the growth, invasion, and migration of OS cells. In contrast, decreasing circ-LMO7 expression had opposite effects. Furthermore, miR-21-5p was predicted to be sponged by circ-LMO7, and had an opposite role of circ-LMO7 in OS. Moreover, ARHGAP24 served as miR-21-5pʹs downstream target. Mechanistically, circ-LMO7 was packed in exosomes and acted as a cancer-suppresser on OS by sponging miR-21-5p and upregulating the expression of ARHGAP24. The exosomal circ-LMO7 expression was significantly decreased in OS cell exosomes, and co-culture experiments showed that exosomal circ-LMO7 suppressed the proliferation ability of OS cells. Circ-LMO7 exerts as a tumor suppressor in OS, and the circ-LMO7/miR-21-5P/ARHGAP24 axis is involved in OS progression.

Abstract Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs characterized by their lack of 5′ caps and 3′ poly(A) tails. These molecules have garnered substantial attention from the scientific community. A wide range of circRNA types has been found to be expressed in various tissues of the human body, exhibiting unique characteristics such as high abundance, remarkable stability, and tissue-specific expression patterns. These attributes, along with their detectability in liquid biopsy samples such as plasma, position circRNAs an ideal choice as cancer diagnostic and prognostic biomarkers. Additionally, several studies have reported that the functions of circRNAs are associated with tumor proliferation, metastasis, and drug resistance. They achieve this through various mechanisms, including modulation of parental gene expression, regulation of gene transcription, acting as microRNA (miRNA) sponges, and encoding functional proteins. In recent years, a large number of studies have focused on synthesizing circRNAs in vitro and delivering them to tumor tissue to exert its effects in inhibit tumor progression. Herein, we briefly discuss the biogenesis, characteristics, functions, and detection of circRNAs, emphasizing their clinical potential as biomarkers for cancer diagnosis and prognosis. We also provide an overview the recent techniques for synthesizing circRNAs and delivery strategies, and outline the application of engineered circRNAs in clinical cancer therapy.

Abstract Increased fatty acid synthesis benefits glioblastoma malignancy. However, the coordinated regulation of cytosolic acetyl-CoA production, the exclusive substrate for fatty acid synthesis, remains unclear. Here, we show that proto-oncogene tyrosine kinase c-SRC is activated in glioblastoma and remodels cytosolic acetyl-CoA production for fatty acid synthesis. Firstly, acetate is an important substrate for fatty acid synthesis in glioblastoma. c-SRC phosphorylates acetyl-CoA synthetase ACSS2 at Tyr530 and Tyr562 to stimulate the conversion of acetate to acetyl-CoA in cytosol. Secondly, c-SRC inhibits citrate-derived acetyl-CoA synthesis by phosphorylating ATP-citrate lyase ACLY at Tyr682. ACLY phosphorylation shunts citrate to IDH1-catalyzed NADPH production to provide reducing equivalent for fatty acid synthesis. The c-SRC-unresponsive double-mutation of ACSS2 and ACLY significantly reduces fatty acid synthesis and hampers glioblastoma progression. In conclusion, this remodeling fulfills the dual needs of glioblastoma cells for both acetyl-CoA and NADPH in fatty acid synthesis and provides evidence for glioma treatment by c-SRC inhibition.

To obtain a more comprehensive understanding of the hotspots and research progress of tea beverage at home and abroad, this research paper analyzed the annual publication volume, author co-occurrences, co-citations, research institutions, the number of country publications, journals, and research hotspots of 1247 English literature collected by WOS from 2002 to 2022 using the Web of Science core collection database as the data source and the visual data analysis software CiteSpace v 6.1.6R. The results of the analysis showed that the heat for research on tea beverage at home and abroad continued to rise, and the annual number of publications showed a rising trend year by year. The number of core authors with more than four articles was 584, accounting for 82.4% of the total number of authors. The majority of institutional publications came from Chinese universities, of which the first institution with the highest number of publications was Anhui Agricultural University. The People's Republic of China was the most actively published country, followed by USA and JAPAN. The journals with high publication volume were mainly concentrated in the field of agricultural and food chemistry, and Journal of Agricultural and Food Chemistry was the journal with the highest co-citation frequency, with a total of 988 citations. The "caffeine" "acid" and "catechin" were high-frequency keywords in tea beverage research, with research hotspots focusing on the detection and extraction of active substances in tea beverage, fermented teas, antioxidant and antibacterial activities. In summary, research on tea beverage was still on the rise, but existing studies suffered from a lack of cooperation among authors, limited research areas and convergent research methods, etc. Scholars should strengthen multifaceted cooperation and communication to broaden the breadth and depth of the research, and to jointly promote the development of research in this field. This study provided a reference for a more in-depth understanding of the current status of global tea beverage research in the future.

Abstract Background Decreased strength and increased stiffness of the quadriceps have been associated with a higher risk of developing knee osteoarthritis (OA) in elders. Dynamic joint stiffness (DJS) represents collective resistance from active and passive knee structures for dynamic knee motions. Elevated sagittal knee DJS has been associated with worsening of cartilage loss in knee OA patients. Altered quadriceps properties may affect DJS, which could be a mediator for associations between quadriceps properties and knee OA. Hence, this study aimed to examine whether DJS and quadriceps properties would be associated with the development of clinical knee OA over 24 months, and to explore the mediation role of DJS in associations between quadriceps properties and knee OA. Methods This was a prospective cohort study with 162 healthy community-dwelling elders. Gait analysis was conducted to compute DJS during the loading response phase. Quadriceps strength and stiffness were evaluated using a Cybex dynamometer and shear-wave ultrasound elastography, respectively. Knee OA was defined based on clinical criteria 24 months later. Logistic regression with generalized estimating equations was used to examine the association between quadriceps properties and DJS and incident knee OA. Mediation analysis was performed to explore the mediation role of DJS in associations between quadriceps properties and the incidence of knee OA. Results A total of 125 participants (65.6 ± 4.0 years, 58.4% females) completed the 24-month follow-up, with 36 out of 250 knees identified as clinical knee OA. Higher DJS (OR = 1.86, 95%CI: 1.33–2.62), lower quadriceps strength (1.85, 1.05–3.23), and greater quadriceps stiffness (1.56, 1.10–2.21) were significantly associated with a higher risk of clinical knee OA. Mediation analysis showed that the DJS was not a significant mediator for the associations between quadriceps properties and knee OA. Conclusions Higher sagittal knee dynamic joint stiffness, lower quadriceps strength, and greater quadriceps stiffness are potential risk factors for developing clinical knee OA in asymptomatic elders. Associations between quadriceps properties and knee OA may not be mediated by dynamic joint stiffness. Interventions for reducing increased passive properties of the quadriceps and knee joint stiffness may be beneficial for maintaining healthy knees in the aging population.

Abstract Background We described a case of abdominal aortic aneurysm complicated by type B thoracic aortic dissection, in whom molecular analysis revealed a pathogenic TGFBR1 missense mutation. Case presentation A 36-year-old woman was admitted to our hospital with sudden onset of back pain. Computed tomography angiogram demonstrated descending aortic dissection extending into the abdominal aorta aneurysm. Whole-exome sequencing and subsequent Sanger sequencing confirmed a pathogenic mutation in the TGFBRI gene (NM_004612.4: c.605C > T; p.Ala202Val). She refused to receive surgery and died one month later. Conclusion To our knowledge, this is the first documented case of the TGFBR1 gene mutation who suffered from abdominal aortic aneurysm complicated by descending thoracic aortic dissection. Her rapid death underscores the importance of timely intervention in TGFBR1 mutation-positive patients.

Abstract Objectives The aim of this study was to evaluate the characteristics of immunocyte associated with bloodstream infection (BSI) caused by Klebsiella pneumoniae (Kpn). Methods Patients with BSI-Kpn were included from 2015 to 2022 in our hospital. Immunocyte subpopulations of enrolled BSI-Kpn patients were tested on the same day of blood culture using multicolor flow cytometry analysis. Antibiotic susceptibility test was determined by agar dilution or broth dilution method. All included isolates were subjected to whole genome sequencing and comparative genomics analysis. Clinical and genetic data were integrated to investigate the risk factors associated with clinical outcome. Results There were 173 patients with non-duplicate BSI-Kpn, including 81 carbapenem-resistant Kpn (CRKP), 30 extended-spectrum β-lactamases producing Kpn (ESBL-Kpn), 62 none CRKP or ESBL-Kpn (S-Kpn). Among 68 ST11-CRKP isolates, ST11-O2v1:KL64 was the most common serotypes cluster (77.9%, 53/68), followed by ST11-OL101: KL47 (13.2%, 9/68). Compared with CSKP group, subpopulations of immunocyte in patients with CRKP were significantly lower (P

Abstract As the second most common malignant tumor in the urinary system, renal cell carcinoma (RCC) is imperative to explore its early diagnostic markers and therapeutic targets. Numerous studies have shown that AURKB promotes tumor development by phosphorylating downstream substrates. However, the functional effects and regulatory mechanisms of AURKB on clear cell renal cell carcinoma (ccRCC) progression remain largely unknown. In the current study, we identified AURKB as a novel key gene in ccRCC progression based on bioinformatics analysis. Meanwhile, we observed that AURKB was highly expressed in ccRCC tissue and cell lines and knockdown AURKB in ccRCC cells inhibit cell proliferation and migration in vitro and in vivo. Identified CDC37 as a kinase molecular chaperone for AURKB, which phenocopy AURKB in ccRCC. AURKB/CDC37 complex mediate the stabilization of MYC protein by directly phosphorylating MYC at S67 and S373 to promote ccRCC development. At the same time, we demonstrated that the AURKB/CDC37 complex activates MYC to transcribe CCND1, enhances Rb phosphorylation, and promotes E2F1 release, which in turn activates AURKB transcription and forms a positive feedforward loop in ccRCC. Collectively, our study identified AURKB as a novel marker of ccRCC, revealed a new mechanism by which the AURKB/CDC37 complex promotes ccRCC by directly phosphorylating MYC to enhance its stability, and first proposed AURKB/E2F1-positive feedforward loop, highlighting AURKB may be a promising therapeutic target for ccRCC.

Abstract Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation. However, ASIC3 is dispensable for IL-23-induced psoriatic inflammation that bypasses the need for nociceptors. Mechanistically, ASIC3 activation induces the activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons to promote neurogenic inflammation. Botulinum neurotoxin A and CGRP antagonists prevent sensory neuron-mediated exacerbation of psoriatic inflammation to similar extents as Asic3 KO. In contrast, replenishing CGRP in the skin of Asic3 KO mice restores the inflammatory response. These findings establish sensory ASIC3 as a critical constituent in psoriatic inflammation, and a promising target for neurogenic inflammation management.

In order to solve the prediction problem of the roof settlement in the unsupported period of roadway excavation in the deep roadway engineering of coal mines, the support vector machine (SVM) tool of artificial intelligence was introduced. Combined with the sparrow search optimization algorithm (SSA), a prediction model of the roof settlement during its unsupported period based on SSA-SVM was proposed. Taking the displacement data during the roof’s unsupported period in the deep underground roadway excavation process of the Great Wall No.5 Mine in Inner Mongolia as a sample, six influencing factors including uniaxial compressive strength (UCS), rock integrity (RQD), ground stress, roadway width-span ratio, non-support roof time and artificial mining were selected. The comprehensive influence weights of the data were summarized through applicability, correlation and classification consistency evaluation. The accuracy of ten-fold cross-validation was used as the fitness function to train and test the SSA-SVM prediction model with different population numbers. The optimal parameter model of population number was selected by error correlation coefficient (RMSE, MAPE, R2), ROC curve, AUC ± Std, running time and standard deviation rate η. The model was applied to the 1902S return airway to predict the settlement of the roadway during the roof’s unsupported period, and compared with the actual mine pressure monitoring data of the roadway. The results show that the prediction performance of SSA-SVM model is better when the population number is 90. The RMSE of training samples is 0.0165, MAPE is 22.54%, and R2 is 0.8295. The RMSE of the test sample is 0.0156, MAPE is 22.37%, and R2 is 0.8490. The realism AUC reaches the maximum of 0.8467, and the standard deviation Std is the minimum of 0.0115. The shortest running time is 8.7239 s and the standard deviation rate is maintained at 0.12%. In the field application of the 1902S return airway, there is no large deviation between the predicted value and the actual value, which is maintained in the range of linear fitting y = 0.90x and y = 1.10x. Both the error correlation coefficient and AUC ± Std satisfy the requirements of test accuracy. The prediction effect of this model can provide an important guidance for subsequent support design and reinforcement of support measures.

In an effort to address the detrimental effects of myocardial ischemia/reperfusion injury (MI/RI), this study introduces a novel therapeutic strategy that involves a microneedle (MN) patch loaded with exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) and carrying small interfering RNA (siRNA) targeting early growth response-1 (EGR1). By delivering hUCMSCs-derived exosomes containing EGR1 siRNA (hUCMSCs-Exosi-EGR1), the MN patch demonstrated promising cardioprotective effects in both in vitro and in vivo models of MI/RI. The results highlighted the efficacy of Exosi-EGR1 in enhancing cardiomyocyte viability, attenuating oxidative stress levels, and fostering mitophagy regulation. Moreover, the Exosi-EGR1 MN patch exhibited excellent mechanical properties and sustained drug release characteristics when embedded in a Gelatin methacryloyl (GelMA) matrix. Noteworthy outcomes from in vivo experiments included significant improvements in cardiac function, reduced cardiac fibrosis, and decreased apoptosis rates in MI/RI mice, emphasizing the potential therapeutic value of the Exosi-EGR1 MN patch in mitigating MI/RI through modulation of oxidative stress and mitophagy mechanisms.

Abstract Mortality rates due to lung cancer are high worldwide. Although PD‐1 and PD‐L1 immune checkpoint inhibitors boost the survival of patients with non‐small‐cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build‐up and potential lysine‐lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non‐histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi‐omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl‐APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti‐APOC2K70‐lac antibody that sensitized anti‐PD‐1 therapy in vivo is developed. This findings highlight the potential of anti lactyl‐APOC2‐K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.

Snowfall/cover and snowmelt are essential determinants of winter soil processes/events that may force the biogeochemical dynamics of soils in temperate regions. Increasing variability of the European hydroclimate is expected to lead to more frequent intermittent warm periods, which cause snowmelt during winter and rapidly mobilize large amounts of dissolved organic matter (DOM). This study, conducted at the Hainich Critical Zone Exploratory in Germany, seeks to address a significant gap in understanding the molecular impacts of snowmelt-induced DOM flows and their ability to alter soil ecosystems rapidly. During two snowmelt events between January and March 2021, we observed that DOM concentration and composition varied more in forest soil seepage than in grassland soil seepage. Forest seepage showed a pronounced DOM flux peak and synchronous increases in the relative abundances of aromatic DOM components, indicating surface-derived transport of plant litter carbon. In the grassland, however, peak DOM fluxes were characterized by a marked increase in nitrogen-containing (N-containing) DOM components, indicating a predominance of microbial carbon. Notably, the unique DOM components specific to each ecosystem increased during peak fluxes in the forest but decreased in the grassland. We suggest that an overall higher molecular richness and the broader functional metabolic potentials in grassland may account for its relatively greater DOM stability compared to the forest during peak snowmelt events.

Cordyceps militaris is a filamentous fungus used for both medicinal and culinary purposes. It exhibits a wide range of pharmacological activities due to its valuable contents of cordycepin, polysaccharides, carotenoids, terpenoids and other metabolites. However, C. militaris strains are highly susceptible to irreversible degradation in agricultural production, which is often manifested as a prolonged color change period and a significant decrease in the production of secondary metabolites. UDP-glycosyltransferases are an important enzyme family that participates in the synthesis of terpenoids by performing the glycosylation of key residues of enzymes or molecules. However, few studies have focused on its effect on the regulation of metabolite production in C. militaris. Therefore, in this study, we performed transcriptome analysis across four different developmental stages of C. militaris to target the putative glycosyltransferase gene CmUGT1, which plays important roles in metabolite production. We further constructed and screened a CmUGT1-overexpressing strain by Agrobacterium tumefaciens-mediated infestation of C. militaris spores. The major metabolite production of the wild-type and CmUGT1-overexpressing C. militaris strains was determined after short-term shake-flask cultivation of mycelia. The results showed that the yields of carotenoids and polysaccharides in the mycelia of the CmUGT1-overexpressing strains were 3.8 and 3.4 times greater than those in the mycelia of the wild type, respectively (p

Abstract Ferroelectric materials have important applications in transduction, data storage, and nonlinear optics. Inorganic ferroelectrics such as lead zirconate titanate possess large polarization, though they are rigid and brittle. Ferroelectric polymers are light weight and flexible, yet their polarization is low, bottlenecked at 10 μC cm−2. Here we show poly(vinylidene fluoride) nanocomposite with only 0.94% of self-nucleated CH3NH3PbBr3 nanocrystals exhibits anomalously large polarization (~19.6 μC cm−2) while retaining superior stretchability and photoluminance, resulting in unprecedented electromechanical figures of merit among ferroelectrics. Comprehensive analysis suggests the enhancement is accomplished via delicate defect engineering, with field-induced Frenkel pairs in halide perovskite stabilized by the poled ferroelectric polymer through interfacial coupling. The strategy is general, working in poly(vinylidene fluoride-co-hexafluoropropylene) as well, and the nanocomposite is stable. The study thus presents a solution for overcoming the electromechanical dilemma of ferroelectrics while enabling additional optic-activity, ideal for multifunctional flexible electronics applications.

Abstract Compared to transition metal dichalcogenide (TMD) monolayers, rhombohedral-stacked (R-stacked) TMD bilayers exhibit remarkable electrical performance, enhanced nonlinear optical response, giant piezo-photovoltaic effect and intrinsic interfacial ferroelectricity. However, from a thermodynamics perspective, the formation energies of R-stacked and hexagonal-stacked (H-stacked) TMD bilayers are nearly identical, leading to mixed stacking of both H- and R-stacked bilayers in epitaxial films. Here, we report the remote epitaxy of centimetre-scale single-crystal R-stacked WS2 bilayer films on sapphire substrates. The bilayer growth is realized by a high flux feeding of the tungsten source at high temperature on substrates. The R-stacked configuration is achieved by the symmetry breaking in a-plane sapphire, where the influence of atomic steps passes through the lower TMD layer and controls the R-stacking of the upper layer. The as-grown R-stacked bilayers show up-to-30-fold enhancements in carrier mobility (34 cm2V−1s−1), nearly doubled circular helicity (61%) and interfacial ferroelectricity, in contrast to monolayer films. Our work reveals a growth mechanism to obtain stacking-controlled bilayer TMD single crystals, and promotes large-scale applications of R-stacked TMD.

Abstract Background Osteonecrosis of the femoral head (ONFH) is a common clinical disease. Improper treatment can lead to femoral head collapse and hip joint dysfunction. Core decompression is particularly important for early ONFH. However, subtrochanteric fractures after core decompression cause some clinical problems. Case presentation This article describes a 34-year-old male patient with early ONFH. After core decompression, he suffered a subtrochanteric fracture of the femur while bearing weight on the affected limb when going up stairs. He was subsequently treated with open reduction and intramedullary nail fixation. Conclusion When core decompression is used to treat ONFH, the location or size of the drill hole, whether a tantalum rod or bone is inserted, and partial weight-bearing of the affected limb may directly affect whether a fracture occurs after surgery. It is hoped that this case report can provide a reference for clinical orthopedic surgeons in the treatment of early ONFH.

ABSTRACT Objective: To evaluate objective treatment efficacy and safety, and subjective patient-reported outcomes in patients with complex ureteral strictures (US) undergoing minimally invasive lingual mucosal graft ureteroplasty (LMGU). Materials and Methods: We prospectively enrolled patients underwent robotic or laparoscopic LMGU between May 2020 and July 2022. Clinical success was defined as symptom-free and no radiographic evidence of re-obstruction. Patient-reported outcomes, including health-related quality of life (HRQoL), mental health status and oral health-related quality of life (OHRQoL), were longitudinally evaluated before surgery, 6 and 12 months postoperatively. Results: Overall, 41 consecutive patients were included. All procedures were performed successfully with 32 patients in robotic approach and 9 in laparoscopic. Forty (97.56%) patients achieved clinical success during the median follow-up of 29 (range 15-41) months. Although patients with complex US experienced poor baseline HRQoL, there was a remarkable improvement following LMGU. Specifically, the 6-month and 12-month postoperative scores were significantly improved compared to the baseline (p < 0.05) in most domains. Twenty-eight (68.3%) and 31 (75.6%) patients had anxiety and depression symptoms before surgery, respectively. However, no significant decrease in the incidence of these symptoms was observed postoperatively. Moreover, there was no significant deterioration of OHRQoL at 6 months and 12 months postoperatively when compared to the baseline. Conclusions: LMGU is a safe and efficient procedure for complex ureteral reconstruction that significantly improves patient-reported HRQoL without compromising OHRQoL. Assessing patients’ quality of life enables us to monitor postoperative recovery and progress, which should be considered as one of the criteria for surgical success.

Abstract Background Patients with inflammatory bowel disease (IBD), dysbiosis, and immunosuppression who receive fecal microbiota transplantation (FMT) from healthy donors are at an increased risk of developing bacteremia. This study investigates the efficacy of a mixture of seven short-chain fatty acid (SCFA)-producing bacterial strains (7-mix), the resulting culture supernatant mixture (mix-sup), and FMT for treating experimental ulcerative colitis (UC) and evaluates underlying mechanisms. Methods Utilizing culturomics, we isolated and cultured SCFA-producing bacteria from the stool of healthy donors. We used a mouse model of acute UC induced by dextran sulfate sodium (DSS) to assess the effects of 7-mix, mix-sup, and FMT on intestinal inflammation and barrier function, microbial abundance and diversity, and gut macrophage polarization by flow cytometry, immunohistochemistry, 16S rRNA gene sequencing, and transwell assays. Results The abundance of several SCFA-producing bacterial taxa decreased in patients with UC. Seven-mix and mix-sup suppressed the inflammatory response and enhanced intestinal mucosal barrier function in the mouse model of UC to an extent similar to or superior to that of FMT. Moreover, 7-mix and mix-sup increased the abundance of SCFA-producing bacteria and SCFA concentrations in colitic mice. The effects of these interventions on the inflammatory response and gut barrier function were mediated by JAK/STAT3/FOXO3 axis inactivation in macrophages by inducing M2 macrophage polarization in vivo and in vitro. Conclusions Our approach provides new opportunities to rationally harness live gut probiotic strains and metabolites to reduce intestinal inflammation, restore gut microbial composition, and expedite the development of safe and effective treatments for IBD.

Abstract Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

Abstract Angiogenesis plays an essential role in the microenvironment of hepatocellular carcinoma (HCC). HOXD3 is involved in the metastasis and invasion of HCC cells; Whereas the underlying molecular mechanisms in the microenvironment of HCC remain unknown. Wound healing, transwell invasion, tube formation and spheroid sprouting assays were carried out to identify the effects of HCC-HOXD3-exosomes and genes on the migration of HCC cells. ChIP–PCR was applied to test the binding region of HOXD3 on CCR6, Med15, and CREBBP promoter. Exosome isolation and mRNA-seq were applied to examine the morphological characteristics of exosomes and the contained mRNA in exosomes. Co-IP and Immunofluorescence assays were used to demonstrate the role of CREBBP in the chromatin conformation of CCL20. The nude mice were used to identify the function of genes in regulating migration of HCC in vivo. In this study, integrated cellular and bioinformatic analyses revealed that HOXD3 targeted the promoter region of CCR6 and induced its transcription. CCR6 was delivered by exosomes to endothelial cells and promoted tumour migration. Overexpression of CCR6 promoted metastasis, invasion in HCCs and angiogenesis in endothelial cells (ECs), whereas its downregulation suppressed these functions. The role of HOXD3 in the metastasis and invasion of HCC cells was reversed after the suppression of CCR6. Furthermore, CCL20 was demonstrated as the ligand of CCR6, and its high expression was found in HCC tissues and cells, which was clinically associated with the poor prognosis of HCC. Mechanistically, HOXD3 targets the promoter regions of CREBBP and Med15, which affect CCL20 chromatin conformation by regulating histone acetylation and expression of Pol II to enhance the migration of HCCs. This study demonstrated the function of the HOXD3–CREBBP/Med15–CCL20–CCR6 axis in regulating invasion and migration in HCC, thus providing new therapeutic targets for HCC.

Abstract Background Probiotics are a potentially effective therapy for inflammatory bowel disease (IBD); IBD is linked to impaired gut microbiota and intestinal immunity. However, the utilization of an antibiotic cocktail (Abx) prior to the probiotic intervention remains controversial. This study aims to identify the effect of Abx pretreatment from dextran sulfate sodium (DSS)-induced colitis and to evaluate whether Abx pretreatment has an enhanced effect on the protection of Clostridium butyricum Miyairi588 (CBM) from colitis. Results The inflammation, dysbiosis, and dysfunction of gut microbiota as well as T cell response were both enhanced by Abx pretreatment. Additionally, CBM significantly alleviated the DSS-induced colitis and impaired gut epithelial barrier, and Abx pretreatment could enhance these protective effects. Furthermore, CBM increased the benefit bacteria abundance and short-chain fatty acids (SCFAs) level with Abx pretreatment. CBM intervention after Abx pretreatment regulated the imbalance of cytokines and transcription factors, which corresponded to lower infiltration of Th1 and Th17 cells, and increased Th2 cells. Conclusions Abx pretreatment reinforced the function of CBM in ameliorating inflammation and barrier damage by increasing beneficial taxa, eliminating pathogens, and inducing a protective Th2 cell response. This study reveals a link between Abx pretreatment, microbiota, and immune response changes in colitis, which provides a reference for the further application of Abx pretreatment before microbiota-based intervention.

To address the shortcomings of light detection and ranging (LiDAR) sensors in extracting road surface elevation information in front of a vehicle, a scheme for digital terrain construction based on the fusion of an Inertial Measurement Unit (IMU) and LiDAR perception is proposed. First, two sets of sensor coordinate systems were configured, and the parameters of LiDAR and IMU were calibrated. Then, a terrain construction system based on the fusion perception of IMU and LiDAR was established, and improvements were made to the state estimation and mapping architecture. Terrain construction experiments were conducted in an academic setting. Finally, based on the output information from the terrain construction system, a moving average-like algorithm was designed to process point cloud data and extract the road surface elevation information at the vehicle’s trajectory position. By comparing the extraction effects of four different sliding window widths, the 4 cm width sliding window, which yielded the best results, was ultimately selected, making the extracted road surface elevation information more accurate and effective.

Gaussian beam carries orbital angular momentum with infinite Hebert space distribution, which is expected to realize large-capacity and long-distance transmission of underwater wireless optical communication. To address the problem that Gaussian beam will be dispersed by diffusion and crosstalk after passing through an ocean turbulence channel, resulting in blurring of OAM mode features and difficulty in extracting OAM mode information, this paper proposes a DCNN-RF mode recognition model, which aims to extract the multidimensional feature information of the RGB and HSV of the OAM mode image through a dual-channel CNN, and then optimize the CNN model by combining with Adam optimizer parameters, and finally the extracted multidimensional features are fused by RF classifier and classify the OAM mode. The experimental results show that the DCNN-RF model achieves 100% recognition rate for weak and medium turbulence, and 97% to 99.5% recognition rate for strong turbulence environment. Analyzing the recognition rate analysis of CNN, CNN-SVM, ResNet50-SVM model and DCNN-RF model, DCNN-RF model has more excellent OAM mode detection ability, and the recognition rate of DCNN-RF model reaches 99.5% in the actual OAM experimental system. This will provide a new reference for mode recognition in OAM optical communication.

ObjectiveThe risk factors of PJK (proximal junctional kyphosis) related to AIS (adolescent idiopathic scoliosis) are inconsistent due to heterogeneity in study design, diagnostic criteria, and population. Therefore, the meta-analysis was conducted to investigate the factors affecting PJK after posterior spinal fusion for AIS patients.MethodsWe implemented a systematic search to obtain potential literature relevant to PJK in AIS surgery. Then, a meta-analysis was performed to assess the incidence of PJK and its risk factors.ResultsWe retrieved 542 articles, and 24 articles were included. The PJK incidence was 17.67%. The use of hooks at UIV (upper instrumented vertebrae) (p = 0.001) could prevent PJK. Before surgery, the larger TK (thoracic kyphosis) (p

Introduction: Due to its unique structural features and bioactivities, the lignin-carbohydrate complex (LCC) displays great potential in vast industrial applications. However, the elucidation of how various pretreatment methods affect the structure and bioactivities remains unaddressed.Method: The three pretreatment methods were systematically studied on the variations of structures and bioactivities, and the Gramineae plant, i.e., wheat straw, was adopted in this study. The structures and bioactivities variation caused by different pretreatments were studied in detail.Result and Discussion: The results showed that compared to physical or chemical pretreatments, biological pretreatment was the most effective approach in improving the bioactivities of LCC. The LCC from biological pretreatment (enzymatic hydrolysis, ELCC4) had more functional groups while the lower weight-average molecular weight (Mw) and polydispersity index (PDI) were well-endowed. The highest antioxidant abilities against ABTS and DPPH of ELCC4 were high up to 95% and 84%, respectively. Furthermore, ELCC4 also showed the best ultraviolet (UV)-blocking rate of 96%, which was increased by 6% and 2% compared to LCC8 (physical pretreatment) and LLCC4 (chemical pretreatment). This work prospectively boosts the understanding of pretreatment strategies on the structures and bioactivities variation of LCC and facilitates its utilization as sustainable and biologically active materials in various fields.

Abstract Chemoselective modification of specific residues within a given protein poses a significant challenge, as the microenvironment of amino acid residues in proteins is variable. Developing a universal molecular platform with tunable chemical warheads can provide powerful tools for precisely labeling specific amino acids in proteins. Cysteine and lysine are hot targets for chemoselective modification, but current cysteine/lysine‐selective warheads face challenges due to cross‐reactivity and unstable reaction products. In this study, a versatile fluorescent platform is developed for highly selective modification of cysteine/lysine under biocompatible conditions. Chloro‐ or phenoxy‐substituted NBSe derivatives effectively labeled cysteine residues in the cellular proteome with high specificity. This finding also led to the development of phenoxy‐NBSe phototheragnostic for the diagnosis and activatable photodynamic therapy of GSH‐overexpressed cancer cells. Conversely, alkoxy‐NBSe derivatives are engineered to selectively react with lysine residues in the cellular environment, exhibiting excellent anti‐interfering ability against thiols. Leveraging a proximity‐driven approach, alkoxy‐NBSe probes are successfully designed to demonstrate their utility in bioimaging of lysine deacetylase activity. This study also achieves integrating a small photosensitizer into lysine residues of proteins in a regioselective manner, achieving photoablation of cancer cells activated by overexpressed proteins.

Abstract Climate change is poised to exert a significant impact on species distribution in the future, and Taxus cuspidata as an endangered species is no exception. Predicting the potential distribution of T. cuspidata is essential for decision‐makers to develop conservation policies and explicitly implement conservation measures. In this study, a combined model was employed to predict potentially suitable habitats for T. cuspidata based on extant data of T. cuspidata distributions in northeastern China. Our findings suggest that mean diurnal range (bio2) and isothermality (bio3) were identified as dominant factors influencing T. cuspidata distribution. Under future climate scenarios, suitable habitat areas increased only in the SSP126 scenario in the 2070s, declining in all other scenarios. In all climate scenarios, the centroid of suitable habitats ultimately shows a trend in northward movement. Decreases in suitable habitat predominantly occurred in Yanbian Korean Autonomous Prefecture, Baishan city, and Tonghua city. Overall, this study highlights a projected habitat reduction due to climate change. Recommendations entail the strategic establishment of nature reserves and the implementation of initiatives aimed at population replenishment.

IntroductionNatural plants are valuable resources for exploring new bioactive compounds. Artemisia vulgaris L. is a traditional Chinese medicinal herb that has been historically used for treating multiple diseases. Active compounds isolated and extracted from A. vulgaris L. typically possess immunomodulatory and anti-inflammatory properties. Artemvulactone E (AE) is a new sesquiterpene lactone isolated and extracted from A. vulgaris L. with unclear biological activities.MethodsThe immunoregulatory effects of AE on macrophages were assessed by ELISA, RT-qPCR, immunofluorescence, and western blot assay. The effect of AE on lipopolysaccharide (LPS) -relates signaling pathways was examined by western blot assay. In zebrafish models, the larvae were yolk-microinjected with LPS to establish inflammation model and the effect of AE was evaluated by determining the survival rate, heart rate, yolk sac edema size, neutrophils and macrophages infiltration of zebrafish. The interaction between AE and Toll-like receptor 4 (TLR4) was examined by molecular docking and dynamic stimulation.ResultsAE reduced the expression and secretion of pro-inflammatory cytokines (TNF-α and IL-6), inflammatory mediators iNOS and COX-2, as well as decreases the production of intracellular NO and ROS in LPS-stimulated macrophages. In addition, AE exerted its anti-inflammatory effect synergistically by inhibiting MAPK/JAK/STAT3-NF-κB signaling pathways. Furthermore, AE enhanced the survival rate and attenuated inflammatory response in zebrafish embryos treated with LPS. Finally, the molecular dynamics results indicate that AE forms stable complexes with LPS receptor TLR4 through the Ser127 residue, thus completely impairing the subsequent activation of MAPK-NF-κB signaling.ConclusionAE exhibits notable anti-inflammatory activity and represents as a potential agent for treating inflammation-associated diseases.

Platelet-rich plasma (PRP), a blood product containing high concentrations of platelets, has been increasingly used for the treatment of a number of diseases because of its anti-inflammatory and regenerative properties. PRP is generally obtained from the patient’s own peripheral blood when used in clinical applications, but allogeneic PRP extracted from umbilical cord blood has also attracted attention due to its unique advantages. The main purpose of this narrative review was to summarize the research and clinical application of cord blood-derived PRP (CB-PRP) in the treatment of diseases up to April 2024. This review also discusses the differences between CB-PRP and autologous PRP (A-PRP). A thorough search of PubMed® and Clinicaltrials.gov identified 13 articles and four clinical trials. To date, CB-PRP has been primarily studied in the fields of orthopaedics, dermatology, neurology, obstetrics/gynaecology and ophthalmology. This is likely to be because this research is relatively novel. Considering the differences between the characteristics of A-PRP and CB-PRP, it is thought that CB-PRP might hold more promise for broader applications in the future.