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Abstract We evaluate deconvolution methods, which infer levels of immune infiltration from bulk expression of tumor samples, through a community-wide DREAM Challenge. We assess six published and 22 community-contributed methods using in vitro and in silico transcriptional profiles of admixed cancer and healthy immune cells. Several published methods predict most cell types well, though they either were not trained to evaluate all functional CD8+ T cell states or do so with low accuracy. Several community-contributed methods address this gap, including a deep learning-based approach, whose strong performance establishes the applicability of this paradigm to deconvolution. Despite being developed largely using immune cells from healthy tissues, deconvolution methods predict levels of tumor-derived immune cells well. Our admixed and purified transcriptional profiles will be a valuable resource for developing deconvolution methods, including in response to common challenges we observe across methods, such as sensitive identification of functional CD4+ T cell states.

Abstract Ferroptosis, an iron-dependent regulated cell death mechanism, holds significant promise as a therapeutic strategy in oncology. In the current study, we explored the regulatory effects of epigallocatechin gallate (EGCG), a prominent polyphenol in green tea, on ferroptosis and its potential therapeutic implications for non-small cell lung cancer (NSCLC). Treatment of NSCLC cell lines with varying concentrations of EGCG resulted in a notable suppression of cell proliferation, as evidenced by a reduction in Ki67 immunofluorescence staining. Western blot analyses demonstrated that EGCG treatment led to a decrease in the expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) while increasing the levels of acyl-CoA synthetase long-chain family member 4 (ACSL4). These molecular changes were accompanied by an increase in intracellular iron, malondialdehyde (MDA), and reactive oxygen species (ROS), alongside ultrastructural alterations characteristic of ferroptosis. Through small RNA sequencing and RT-qPCR, transfer RNA-derived small RNA 13502 (tsRNA-13502) was identified as a significant target of EGCG action, with its expression being upregulated in NSCLC tissues compared to adjacent non-tumorous tissues. EGCG was found to modulate the ferroptosis pathway by downregulating tsRNA-13502 and altering the expression of key ferroptosis regulators (GPX4/SLC7A11 and ACSL4), thereby promoting the accumulation of iron, MDA, and ROS, and ultimately inducing ferroptosis in NSCLC cells. This study elucidates EGCG’s multifaceted mechanisms of action, underscoring the modulation of ferroptosis as a viable therapeutic approach for enhancing NSCLC treatment outcomes.

Abstract Background Endogenous endophthalmitis (EE) is a rare but highly destructive eye emergency secondary to systemic infection. Acute endophthalmitis can lead to irreversible vision impairment or even loss of the whole eye, unless being diagnosed and treated promptly. Case presentation This study reports three typical EE cases of endogenous endophthalmitis secondary to different severe systemic diseases. Patients were recruited from the Department of ophthalmology at Zhongnan hospital of Wuhan University and the Department of ophthalmology at the Second Affiliated Hospital of Fujian Medical University. Patients were followed up for up to 60 days. Among these cases, the eye symptoms is the initial manifestations while secondary to original different special systemic conditions. Patients have been treated under dynamically prompt response undergoing systemic treatment and eye treatment at the same time. Best corrected visual acuity were 20/40, 20/60 and light perception during follow-up evaluation. Conclusions Our observation suggest that prompt identification and treatment could save patients’ vision from EE.

In this study, a novel fluorine-containing carbon nanosphere was synthesized by high-temperature carbonization of waste fluororubber trimmings, and its mixing method with fluororubber was investigated. It was found that the solution mixing method resulted in the highest tensile strength (7.6 %) and modulus at 100 % strain (13.3 %) of fluororubber compared to the mechanical mixing method. Furthermore, the addition of fluorine-containing carbon nanosphere can significantly enhance fluororubber's heat resistance, inhibit its thermal degradation, and increase its ultimate service temperature (266.3 °C, 2 years). This work provides new insights into the preparation of high-performance fluororubber composites.

Background: While numerous studies have examined the influence of perineural dexamethasone on nerve block duration, its potential impact on postoperative nerve injury has not been adequately addressed. Objective: This study aims to elucidate the effect of perineural dexamethasone on nerve injury and nerve function recovery after surgery. Design: A prospective randomized double-blinded trial. Setting: The First Affiliated Hospital of Chengdu Medical College, Chengdu, China. The study was conducted between 14 June and 30 December 2022. Participants: Patients aged 18 – 80 years, ASA I - II, scheduled for elective orthopedic or burn and plastic surgery. Interventions: Patients were randomized to receive either perineural dexamethasone (D group) or no dexamethasone (ND group). Main outcome measures: Primary outcomes were the incidence and recovery of nerve injury. Secondary outcomes included postoperative pain scores, analgesic consumption, and adverse events. Results: Initial postoperative nerve injury rates were similar between groups (D: 30.4 %, ND: 33.3 %, P > 0.05). At 12 weeks post-discharge, significantly more patients in the ND group recovered from nerve deficits (78.8 % vs 60.3 %; OR = 2.45, 95 % CI = 1.05 – 5.72, P

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder that affects the central nervous system (CNS). Neuroinflammation is a crucial factor in the pathological advancement of PD. PD is characterized by the presence of activated microglia and increased levels of proinflammatory factors, which play a crucial role in its pathology. During the immune response of PD, microglia regulation is significantly influenced by microRNA (miRNA). The excessive activation of microglia, persistent neuroinflammation, and abnormal polarization of macrophages in the brain can be attributed to the dysregulation of certain miRNAs. Additionally, there are miRNAs that possess the ability to inhibit neuroinflammation. miRNAs, which are small non-coding epigenetic regulators, have the ability to modulate microglial activity in both normal and abnormal conditions. They also have a significant impact on promoting communication between neurons and microglia.

Fluororubber (FKM) is an irreplaceable sealing material that plays a critical role in new energy vehicles, petrochemical and aerospace industries. Their broad applications arise from the excellent thermal stability and solvent resistance of fluororubber. Despite there are increasing number of reports on preparation methods, properties and characterization of FKM in literature, there is still a lack of a thorough and comprehensive review that summarizes these results. This paper provides an overview of FKM types, preparation methods, property testing and microscopic characterization, and attempts to give a comprehensive introduction to the vulcanization mechanism of FKM using ternary fluororubber. The mechanical mixing method was identified as the most versatile preparation method in the review, but it is susceptible to causing agglomeration of nanomaterials. Furthermore, different vulcanization systems and reinforcing fillers can be chosen based on the application direction of FKM. Carbon nanomaterials with high inherent strength have the best reinforcing effect on FKM, although they also exhibit the most significant self-agglomeration effect. This can be mitigated through synergistic use of fillers of multiple dimensions and interfacial modification in future research. Additionally, current challenges and future prospects for FKM nanocomposites are also discussed.

Abstract The development of highly efficient electrocatalysts for direct seawater splitting with bifunctionality for inhibiting anodic oxidation reconstruction and selective oxygen evolution reactions is a major challenge. Herein, we report a direct seawater oxidation electrocatalyst that achieves long-term stability for more than 1000 h at 600 mA/cm2@η600 and high selectivity (Faraday efficiency of 100%). This catalyst revolves an amorphous molybdenum oxide layer constructed on the beaded-like cobalt oxide interface by atomic layer deposition technology. As demonstrated, a new restricted dynamic surface self-reconstruction mechanism is induced by the formation a stable reconstructed Co-Mo double hydroxide phase interface layer. The device assembled into a two-electrode flow cell for direct overall seawater electrolysis maintained at 1 A/cm2@1.93 V for 500 h with Faraday efficiency higher than 95%. Hydrogen generation rate reaches 419.4 mL/cm2/h, and the power consumption (4.62 KWh/m3 H2) is lower than that of pure water (5.0 KWh/m3 H2) at industrial current density.

Abstract Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor cells. Cancer cells could exhibit a “neural addiction” property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through nerve growth factor-mediated axonogenesis. Targeting the dysregulated nervous systems might represent a novel strategy for cancer treatment. However, whether intrahepatic cholangiocarcinoma (ICC) could build its own nerve networks and the role of neurotransmitters in the progression ICC remains largely unknown. Immunofluorescence staining and Enzyme-linked immunosorbent assay suggested that ICC cells and the infiltrated nerves could generate a tumor microenvironment rich in acetylcholine that promotes ICC metastasis by inducing epithelial-mesenchymal transition (EMT). Acetylcholine promoted ICC metastasis through interacting with its receptor, alpha 5 nicotine acetylcholine receptor subunits (CHRNA5). Furthermore, acetylcholine/CHRNA5 axis activated GSK3β/β-catenin signaling pathway partially through the influx of Ca2+-mediated activation of Ca/calmodulin-dependent protein kinases (CAMKII). In addition, acetylcholine signaling activation also expanded nerve infiltration through increasing the expression of Brain-Derived Neurotrophic Factor (BDNF), which formed a feedforward acetylcholine-BDNF axis to promote ICC progression. KN93, a small-molecule inhibitor of CAMKII, significantly inhibited the migration and enhanced the sensitivity to gemcitabine of ICC cells. Above all, Acetylcholine/CHRNA5 axis increased the expression of β-catenin to promote the metastasis and resistance to gemcitabine of ICC via CAMKII/GSK3β signaling, and the CAMKII inhibitor KN93 may be an effective therapeutic strategy for combating ICC metastasis.

Abstract Cancer cell growth, metastasis, and drug resistance pose significant challenges in the management of lung adenocarcinoma (LUAD). However, there is a deficiency in optimal predictive models capable of accurately forecasting patient prognoses and guiding the selection of targeted treatments. Programmed cell death (PCD) pathways play a pivotal role in the development and progression of various cancers, offering potential as prognostic indicators and drug sensitivity markers for LUAD patients. The development and validation of predictive models were conducted by integrating 13 PCD patterns with comprehensive analysis of bulk RNA, single-cell RNA transcriptomics, and pertinent clinicopathological details derived from TCGA-LUAD and six GEO datasets. Utilizing the machine learning algorithms, we identified ten critical differentially expressed genes associated with PCD in LUAD, namely CHEK2, KRT18, RRM2, GAPDH, MMP1, CHRNA5, TMPRSS4, ITGB4, CD79A, and CTLA4. Subsequently, we conducted a programmed cell death index (PCDI) based on these genes across the aforementioned cohorts and integrated this index with relevant clinical features to develop several prognostic nomograms. Furthermore, we observed a significant correlation between the PCDI and immune features in LUAD, including immune cell infiltration and the expression of immune checkpoint molecules. Additionally, we found that patients with a high PCDI score may exhibit resistance to immunotherapy and standard adjuvant chemotherapy regimens; however, they may benefit from other FDA-supported drugs such as docetaxel and dasatinib. In conclusion, the PCDI holds potential as a prognostic signature and can facilitate personalized treatment for LUAD patients.

Abstract Background Hepatocellular carcinoma (HCC) is closely associatedwith chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified. Methods In silico, proteomic and pathological assessment of alteration of cirrhotic-ECM were applied in clinical cohort. Multiple pre-clinical models with ECM manipulation were used to evaluate cirrhotic-ECM’s effect on ICI treatment. In silico, flow cytometry and IHC were applied to explore how cirrhotic-ECM affect HCC microenvironment. In vitro and in vivo experiments were carried out to identify the mechanism of how cirrhotic-ECM undermined ICI treatment. Results We defined “a pro-tumor cirrhotic-ECM” which was featured as the up-regulation of collagen type 1 (Col1). Cirrhotic-ECM/Col1 was closely related to impaired T cell function and limited anti PD-1 (aPD-1) response of HCC patients from the TCGA pan cancer cohort and the authors’ institution, as well as in multiple pre-clinical models. Mechanically, cirrhotic-ECM/Col1 orchestrated an immunosuppressive microenvironment (TME) by triggering Col1-DDR1-NFκB-CXCL8 axis, which initiated neutrophil extracellular traps (NETs) formation to shield HCC cells from attacking T cells and impede approaching T cells. Nilotinib, an inhibitor of DDR1, reversed the neutrophils/NETs dominant TME and efficiently enhanced the response of HCC to aPD-1. Conclusions Cirrhotic-ECM modulated a NETs enriched TME in HCC, produced an immune suppressive TME and weakened ICI efficiency. Col1 receptor DDR1 could be a potential target synergically used with ICI to overcome ECM mediated ICI resistance. These provide a mechanical insight and novel strategy to overcome the ICI resistance of HCC.

Abstract This work prepared and investigated the impact of carboxymethyl chitosan nanoparticles (MC-NPs) on the proliferative capability of keloid fibroblasts (KFBs) while analyzing the mechanistic roles of miR-214 and adenosine A2A receptor (A2AR) in fibroblasts within hypertrophic scars. MC-NPs were synthesized through ion cross-linking, were characterized using transmission electron microscopy (TEM) and laser particle size scattering. The influence of MC-NPs on the proliferation capacity of KFBs was assessed using the MTT method. Changes in the expression levels of miR-214 and A2AR in KFBs, normal skin fibroblasts (NFBs), hypertrophic scar tissue, and normal skin tissue were analyzed. KFBs were categorized into anti-miR-214, anti-miR-NC, miR-214 mimics, miR-NC, si-A2AR, si-con, anti-miR-214+ si-con, and anti-miR-214+ si-A2AR groups. Bioinformatics target prediction was conducted to explore the interaction between miR-214 and A2AR. Real-time quantitative PCR and immunoblotting (WB) were employed to detect the expression levels of miR-214, A2AR, apoptotic protein Bax, and TGF-β in different cells. Cell counting kit-8 (CCK8) and flow cytometry were employed to assess cell proliferation activity and apoptosis. The results indicated that MC-NPs exhibited spherical particles with an average diameter of 236.47 ± 4.98 nm. The cell OD value in the MC-NPs group was lower than that in KFBs (P

Mycoplasma gallisepticum (MG) is a pathogen that induces chronic respiratory illnesses in chickens, leading to tracheal and lung injury, and eliciting immune reactions that support sustained colonization. Baicalin, a compound found in scutellaria baicalensis, exhibits anti-inflammatory, antioxidant, and antibacterial properties. This study aimed to investigate the potential of baicalin in alleviating lung and cell damage caused by MG by restoring imbalances in M1/M2 and Th1/Th2 differentiation and to explore its underlying mechanism. In this research, a model for M1/M2 polarization induced by MG was initially developed. Specifically, infection with MG at a multiplicity of infection (MOI) of 400 for 6 h represented the M1 model, while infection for 10 h represented the M2 model. The polarization markers were subsequently validated using qRT-PCR, ELISA, and Western blot analysis. Baicalin disrupts the activation of M1 cells induced by MG and has the potential to restore the balance between M1 and M2 cells, thereby mitigating the inflammatory damage resulting from MG. Subsequent studies on MG-infected chickens detected imbalances in M1/M2 and Th1/Th2 differentiation in alveolar lavage fluid, as well as imbalances in macrophages and Th cells in the lung. The M1/Th1 model was exposed to MG for 5 d, while the M2/Th2 model was infected with MG for 7 d. The utilization of both light and electron transmission microscopes revealed that the administration of baicalin resulted in a reduction in the number of M1 cells, a decrease in cytoplasmic vacuoles, restoration of mitochondrial swelling and chromatin agglutination, as well as alleviation of alveolar rupture and inflammatory cell infiltration. Furthermore, baicalin restored MG-induced M1/M2 and Th1/Th2 imbalances and inhibited the phosphorylation of p38 and p65 proteins, thereby hindering the activation of the TLR4-p38 MAPK/NF-κB pathway. This study provides insights into the potential long-term effects of baicalin in MG infection and offers a theoretical basis for practical applications.

Objectives Decreased prognostic nutritional index (PNI) was associated with adverse outcomes in many clinical diseases. This study aimed to evaluate the relationship between baseline PNI value and adverse clinical outcomes in patients with coronary artery disease (CAD).Design The Personalized Antiplatelet Therapy According to CYP2C19 Genotype in Coronary Artery Disease (PRACTICE) study, a prospective cohort study of 15 250 patients with CAD, was performed from December 2016 to October 2021. The longest follow-up period was 5 years. This study was a secondary analysis of the PRACTICE study.Setting The study setting was Xinjiang Medical University Affiliated First Hospital in China.Participants Using the 50th and 90th percentiles of the PNI in the total cohort as two cut-off limits, we divided all participants into three groups: Q1 (PNI

Abstract The commercialization of Li−S batteries is seriously hindered by polysulfides with severe shuttle effect, and the inherent insulating properties and slow reaction kinetics of insoluble Li2S products. Transition metal sulfides (TMSs) have a high adsorption capacity for polysulfides and have been shown to have a strong catalytic effect on polysulfide conversion reactions. This paper reviews the research on the application of Unary TMSs, heterostructures, etc. in Li−S batteries, and gives some research methods for TMD catalysts in Li−S batteries. Finally, it points out the main focuses and direction of future Li−S battery research and development. It aims to provide some insights into the design and manufacture of advanced Li−S batteries for commercial use.

ObjectiveThe non-motor symptoms of Parkinson’s disease (PD) are an important part of PD. In recent years, more and more non-drug interventions have been applied to alleviate the non-motor symptoms of PD, but the relevant evidence is limited. This systematic review and meta-analysis was designed to evaluate the efficacy of non-drug interventions in patients with non-motor symptoms in patients with PD.MethodsSeven databases, including Pubmed, Embease, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database (WANFANG), VIP database (VIP), and China Biomedical Literature Service System (CBM) were searched from the establishment of the database to December 2023. Non-drug interventions such as acupuncture, cognitive behavioral therapy (CBT), exercise, repetitive transcranial magnetic stimulation (rTMS), and non-motor symptoms of Parkinson’s disease were selected as search words, and two independent evaluators evaluated the included literature’s bias risk and data extraction. The therapeutic efficacy was evaluated by the Parkinson’s Disease Sleep Scale (PDSS), Hamilton Depression Scale (HAMD), Beck Depression Inventory (BDI), Hamilton Anxiety Scale (HAMA), Montreal Cognitive Assessment (MoCA), Minimum Mental State Examination (MMSE), and Parkinson’s Disease Questionnaire-39 (PDQ-39). RevMan 5.4.1 (Reviewer Manager Software 5.4.1). Cochrane Collaboration, Oxford, United Kingdom analyzed the data and estimated the average effect and the 95% confidence interval (CI). A heterogeneity test is used to assess differences in the efficacy of different non-drug treatments.ResultsWe selected 36 from 4,027 articles to participate in this meta-analysis, involving 2,158 participants. Our combined results show that: PDSS: [mean difference (MD) = −19.35, 95% CI (−30.4 to −8.28), p

Abstract Recent progress in two-dimensional ferroelectrics greatly expands the versatility and tunability in van der Waals heterostructure based electronics. However, the switching endurance issue that widely plagues conventional ferroelectrics in practical applications is hitherto unexplored for van der Waals layered ferroelectrics. Herein, we report the observation of unusual polarization fatigue behaviors in van der Waals layered CuInP2S6, which also possesses finite ionic conductivity at room temperature. The strong intertwinement of the short-range polarization switching and long-range ionic movement in conjunction with the van der Waals layered structure gives rise to unique morphological and polarization evolutions under repetitive electric cycles. With the help of concerted chemical, structural, lattice vibrational and dielectric analyses, we unravel the critical role of the synergy of ionic migration and surface oxidation on the anomalous polarization enhancement and the eventual polarization degradation. This work provides a general insight into the polarization fatigue characteristics in ionically-active van der Waals ferroelectrics and delivers potential solutions for the realization of fatigue-free capacitors.

Abstract The thriving field of atomic defect engineering towards advanced electrocatalysis relies on the critical role of electric field polarization at the atomic scale. While this is proposed theoretically, the spatial configuration, orientation, and correlation with specific catalytic properties of materials are yet to be understood. Here, by targeting monolayer MoS2 rich in atomic defects, we pioneer the direct visualization of electric field polarization of such atomic defects by combining advanced electron microscopy with differential phase contrast technology. It is revealed that the asymmetric charge distribution caused by the polarization facilitates the adsorption of H*, which originally activates the atomic defect sites for catalytic hydrogen evolution reaction (HER). Then, it has been experimentally proven that atomic-level polarization in electric fields can enhance catalytic HER activity. This work bridges the long-existing gap between the atomic defects and advanced electrocatalysis by directly revealing the angstrom-scale electric field polarization and correlating it with the as-tuned catalytic properties of materials; the methodology proposed here could also inspire future studies focusing on catalytic mechanism understanding and structure-property-performance relationship.

Abstract Background Therapeutic approaches for extrahepatic cholangiocarcinoma (EHCC) are limited, due to insufficient understanding to biomarkers related to prognosis and drug response. Here, we comprehensively assess the molecular characterization of EHCC with clinical implications. Methods Whole‐exome sequencing (WES) on 37 tissue samples of EHCC were performed to evaluate genomic alterations, tumor mutational burden (TMB) and microsatellite instability (MSI). Results Mutation of KRAS (16%) was significantly correlated to poor OS. ERBB2 mutation was associated with improved OS. ERBB2, KRAS, and ARID1A were three potentially actionable targets. TMB ≥10 mutations per megabase was detected in 13 (35.1%) cases. Six patients (16.2%) with MSIsensor scores ≥10 were found. In multivariate Cox analysis, patients with MSIsensor sore exceed a certain threshold (MSIsensor score ≥0.36, value approximately above the 20th percentile as thresholds) showed a significant association with the improved OS (HR = 0.16; 95% CI: 0.056–0.46, p

Abstract Renal ischemia/reperfusion (I/R) injury, which leads to acute kidney injury (AKI), is a major cause of morbidity and mortality in a variety of clinical situations. This study aimed to investigate the protective role of Mfn2 during renal I/R injury. Overexpression of Mfn2 in NRK-52E rat renal tubular epithelial cells and rats, then we constructed hypoxia reoxygenation (H/R) cells and I/R rat model. Apoptosis, ROS, ATP, Ca2+ levels in cells and rats, as well as renal tissue and functional injury in rats were detected respectively. Endoplasmic reticulum (ER) stress was further examined in cells and rats. The morphological changes of mitochondria-associated ER membranes (MAMs) were also detected. Mfn2 expression is reduced in H/R-treated NRK-52E cells and renal tissue of I/R rats. At the cellular level, overexpression of Mfn2 promoted cell proliferation, inhibited cell apoptosis, attenuated mitochondrial damage and Ca2+ overload, and ER stress. In addition, Mfn2 also restored the MAMs structure. In vivo experiments found that overexpression of Mfn2 could improve renal function and alleviate tissue injury. Concomitant with elevated Mfn2 expression in the kidney, reduced renal cell apoptosis, restored mitochondrial function, and reduced calcium overload. Finally, ER stress in rat kidney tissue was alleviated after overexpression of Mfn2. These results reveal that Mfn2 contributes to ER stress, mitochondrial function, and cell death in I/R injury, which provides a novel therapeutic target for AKI.

Abstract Sustainability and adaptability in structural design of the organic cathodes present promises for applications in alkali metal ion batteries. Nevertheless, a formidable challenge lies in their high solubility in organic electrolytes, particularly for small molecular materials, impeding cycling stability and high capacity. This study focuses on the design and synthesis of organic small molecules, the isomers of (E)‐5,5′‐difluoro‐[3,3′‐biindolinylidene]‐2,2′‐dione (EFID) and 3,9‐difluoro‐6,12‐dihydrodibenzo [c, h][2,6]naphthyridine‐5,11‐dione (FBND). While EFID, characterized by a less π‐conjugated structure, exhibits subpar cycling stability in lithium‐ion batteries (LIBs), intriguingly, another isomer, FBND, demonstrates exceptional capacity and cycling stability in LIBs. FBND delivers a remarkable capacity of 175 mAh g−1 at a current density of 0.05 A g−1 and maintains excellent cycling stability over 2000 cycles, retaining 90% of its initial capacity. Furthermore, an in‐depth examination of redox reactions and storage mechanisms of FBND are conducted. The potential of FBND is also explored as an anode in lithium‐ion batteries (LIBs) and as a cathode in sodium‐ion batteries (SIBs). The FBND framework, featuring extended π‐conjugated molecules with an imide structure compared to EFID, proves to be an excellent material template to develop advanced organic small molecular cathode materials for sustainable batteries.

The objective of this study was to examine the characteristics of a nanostructured Yb2SiO5 coating and a conventional Yb2SiO5 coating, both prepared using atmospheric plasma spraying (APS). The investigation focused on the phase composition, microstructure, thermal properties, and fracture toughness of the two types of Yb2SiO5 coatings. The findings revealed that both nanostructured and conventional coatings consisted of Yb2SiO5, Yb2O3, and amorphous phases. The nanostructured Yb2SiO5 coating exhibited lower residual tensile stress compared to the conventional Yb2SiO5 coating, resulting in fewer crack defects in the former. The thermal conductivity of the nanostructured Yb2SiO5 coating ranged from 0.71 to 1.22 W/(m·K) between 200 and 1200 °C, while the conventional Yb2SiO5 coating exhibited a thermal conductivity range of 0.81–1.32 W/(m·K) within the same temperature range. Consequently, the thermal conductivity of the nanostructured Yb2SiO5 coating was lower than that of the conventional counterpart. Furthermore, the presence of nanograins significantly enhanced the fracture toughness of the nanostructured Yb2SiO5 coating, which was found to be 1.7 times greater than that of the conventional Yb2SiO5 coating.

Obtaining cemented carbides with smaller WC grain size and better properties is key to their wider application. Ultrafine cemented carbides were prepared by using spark plasma sintering (SPS) with nano VC-Cr3C2 as nanocomposite grain growth inhibitors (NGGIs) and multi-walled carbon nanotubes (MWCNTs) as reinforcing materials. The effects of NGGIs and MWCNTs on the microstructure and mechanical properties of alloys were evaluated. The results indicated that the specimens (0.5 wt % NGGIs and 0.4 wt % MWCNTs) prepared at 1350 °C for 8 min under a pressure of 50 MPa have enhanced mechanical properties (HV 2520.85 kgf/mm2, KIC 13.26 MPa m1/2) and a homogeneous microstructure. The grain size of WC is suppressed (the average grain size is 200–400 nm). NGGIs can prevent the dissolution of W and C in liquid Co, thereby inhibiting the growth of WC grains. The uniform dispersion of MWCNTs in WC matrix mobilizes their fiber-reinforcement effect. The combination of NGGIs, MWCNTs, and SPS can improve the mechanical properties and optimize the microstructure of the alloy.

Abstract Background Postoperative anemia is a risk factor for adverse surgical outcomes. Our study aimed to assess the role of intravenous iron and erythropoietin therapy for the rapid correction of anemia following orthopedic surgery. Methods Patients undergoing elective orthopedic surgery were prospectively enrolled and randomly divided into three groups: Control (placebo), Group 1 (IV iron monotherapy), and Group 2 [combined IV iron and recombinant human erythropoietin (rHuEPO) therapy]. Blood tests were performed preoperative (baseline) and on postoperative days (PODs) 1, 3, and 7. Results All groups demonstrated significantly lower hemoglobin (Hb) concentrations compared to baseline, with no significant inter-group differences in postoperative Hb concentrations (p > 0.05). Serum erythropoietin, ferritin, and vitamin B12 levels, and reticulocyte count increased beyond normal ranges in all groups. Significantly lower serum iron levels were observed postoperatively in all groups (p 0.05). Conclusion Postoperative treatment with combined intravenous iron and rHuEPO was ineffective in correcting postoperative anemia among orthopedic surgery patients, besides achieving higher reticulocyte counts in the first week of surgery. No improvement in mobilization of storage iron was achieved with rHuEPO. We further suggest against vitamin B12 administration during the early postoperative period.

Abstract Background The oocyte-to-embryo transition (OET) converts terminally differentiated gametes into a totipotent embryo and is critically controlled by maternal mRNAs and proteins, while the genome is silent until zygotic genome activation. How the transcriptome, translatome, and proteome are coordinated during this critical developmental window remains poorly understood. Results Utilizing a highly sensitive and quantitative mass spectrometry approach, we obtain high-quality proteome data spanning seven mouse stages, from full-grown oocyte (FGO) to blastocyst, using 100 oocytes/embryos at each stage. Integrative analyses reveal distinct proteome reprogramming compared to that of the transcriptome or translatome. FGO to 8-cell proteomes are dominated by FGO-stockpiled proteins, while the transcriptome and translatome are more dynamic. FGO-originated proteins frequently persist to blastocyst while corresponding transcripts are already downregulated or decayed. Improved concordance between protein and translation or transcription is observed for genes starting translation upon meiotic resumption, as well as those transcribed and translated only in embryos. Concordance between protein and transcription/translation is also observed for proteins with short half-lives. We built a kinetic model that predicts protein dynamics by incorporating both initial protein abundance in FGOs and translation kinetics across developmental stages. Conclusions Through integrative analyses of datasets generated by ultrasensitive methods, our study reveals that the proteome shows distinct dynamics compared to the translatome and transcriptome during mouse OET. We propose that the remarkably stable oocyte-originated proteome may help save resources to accommodate the demanding needs of growing embryos. This study will advance our understanding of mammalian OET and the fundamental principles governing gene expression.

Metal thickness measurements are essential in various industrial applications, yet current non-contact ultrasonic methods face limitations in range and accuracy, hindering the widespread adoption of electromagnetic ultrasonics. This study introduces a novel combined thickness measurement method employing fuzzy logic, with the aim of broadening the applicational scope of the EMAT. Leveraging minimal hardware, this method utilizes the short pulse time-of-flight (TOF) technique for initial thickness estimation, followed by secondary measurements guided by fuzzy logic principles. The integration of measurements from the resonance, short pulse echo, and linear frequency modulation echo extends the measurement range while enhancing accuracy. Rigorous experimental validation validates the method’s effectiveness, demonstrating a measurement range of 0.3–1000.0 mm with a median error within ±0.5 mm. Outperforming traditional methods like short pulse echoes, this approach holds significant industrial potential.

To satisfy the needs of precision machining, ultrafine tungsten carbide (WC)-based cemented carbide with fine grain size and excellent mechanical properties was prepared. Ultrafine cemented carbide was prepared by spark plasma sintering (SPS) using WC, Co as raw materials and metal elements V, and Cr as additives, and the effects of metal elements on the microstructure and mechanical properties of cemented carbide were investigated. The results show that the specimen (91.6WC-1.2V-1.2Cr-6Co) prepared at 1350 °C, 6 min, 25 MPa has the best mechanical properties (HV 2322.9, KIC 8.7 MPa·m1/2) and homogeneous microstructure. The metal elements could react with WC to form a (W, V, Cr) Cx segregation layer, which effectively inhibits the growth of WC grains (300 nm). The combination of SPS and metal element additives provides a new approach for the preparation of ultrafine cemented carbides with excellent properties.

Ductile cast iron pipes (DCIPs) are widely utilized in water and gas supply due to their exceptional mechanical and material properties. Quality control during production is paramount for optimal performance, with surface defect detection being of utmost importance. Currently, production sites primarily rely on manual visual inspection, which presents several challenges, including high labor intensity, low efficiency, and subjectivity in defect judgment. 2D detection algorithms based on single images struggle to effectively detect small defects such as pores, pinholes, and scratches, resulting in high missed detection rates and vulnerability to interference from oil and water stains. To address these issues, this paper proposes a symmetrical twin-light photometric stereo (TLPS) detection algorithm based on photometric stereo theory, and image correction algorithm for mitigating the effects of ambient light. A visual inspection prototype system was designed and successfully implemented at a production site. The system comprises eight visual inspection units, each equipped with a high-speed line scan camera and two bar light sources for image acquisition of moving DCIP. Under the Lambertian model and parallel light source assumption, the gradient expression in the texture direction of the DCIP surface is derived based on light source symmetry. Production experiment results demonstrate that the gradient map obtained through the proposed TLPS effectively enhances defect contrast and accurately detects and locates micro defects such as pores, pinholes, and scratches on cast pipe surfaces. This verifies the effectiveness of the TLPS algorithm, addresses the shortcomings of traditional 2D detection algorithms, and lays the foundation for subsequent online detection of DCIP surface defects.

It is particularly important to establish more effective and safer antiplatelet treatment strategies according to age. The present subanalysis of the PATH-PCI trial was to determine the safety and efficacy of any dual-antiplatelet therapy (DAPT) strategy in different age groups. We randomized 2285 chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI) into a standard group or a personalized group from December 2016 to February 2018. The personalized group received personalized antiplatelet therapy (PAT) based on a novel platelet function test (PFT). The standard group received standard antiplatelet therapy (SAT). Then, all patients were divided according to age (under the age of 65 years and aged 65 years or over) to investigate the association and interaction of age on clinical outcomes at 180 days. In the patients under the age of 65 years, the incidence of NACEs was decreased in the personalized group compared to the standard group (5.1% vs. 8.8%, HR: 0.603, 95% CI: 0.409–0.888, P = .010). The rates of MACCEs (3.3% vs. 7.7%, HR: 0.450, 95% CI: 0.285–0.712, P = .001), MACEs (2.2% vs. 5.4%, HR: 0.423, 95% CI: 0.243–0.738, P = .002) also decreased. We did not find a significant difference in bleeding between the groups. In the patients aged 65 years or over, no difference in the primary endpoint was found (4.9% vs. 4.2%, P = .702), and comparable rates of survival were observed with the two strategies (all Ps > 0.05). The present study shows that PAT according to PFT was comparable to SAT at the 180-day follow-up for both ischemic and bleeding endpoints in CCS patients aged 65 years or over who underwent PCI. In patients under the age of 65 years, PAT can reduce ischemic events but does not increase bleeding, and it is an effective and safe treatment strategy. It may be necessary for young CCS patients after PCI to undergo PAT early after PCI.

Abstract Background The aberrant expression of BRIP1 was associated with several cancers; however, the panoramic picture of BRIP1 in human tumors remains unclear. This study aims to explore the pan-cancerous picture of the expression of BRIP1 across 33 human cancers. Methods Based on the data from TCGA and GTEx, a series of bioinformatic analyses were applied to systematically explore the genetic landscape and biologic function of BRIP1 in 33 human tumors. Results We observed prognosis-related differential BRIP1 expressions between various carcinomas and the corresponding normal tissues. “Basal transcription factors,” “homologous recombination,” “nucleotide excision repair,” and DNA metabolism pathways may play a role in the functional mechanisms of BRIP1. Patients with uterine corpus endometrial carcinoma presented with the highest alteration frequency of BRIP1 (nearly 10%). Single-nucleotide and copy number variations of BRIP1 were noticed in multiple cancers, and the expression of BRIP1 is significantly regulated by copy number variation in breast invasive carcinoma and lung squamous cell carcinoma. BRIP1 expression is negatively correlated with the DNA methylation levels in many tumors and is associated with the activation of apoptosis, cell cycle, DNA damage response, and inhibition of hormone ER and RNS/MARK signaling pathways. Moreover, a positive correlation was observed between BRIP1 expression and the immune infiltration levels of cancer-associated fibroblasts and CD8+ T cells in lung adenocarcinoma. Conclusion Our pan-cancer analysis of BRIP1 provides a valuable resource for understanding the multimolecular characteristics and biological function of BRIP1 across human cancers.

[Objective] The influences of surface tension fractures caused by coal mining subsidence on the soil quality of cultivated land were analyzed, and the changes in soil nutrients before and after coal mining subsidence were quantified, in order to provide a theoretical basis for the pre-mining and in-mining management of land in the subsidence area. [Methods] The study was conducted in the surface tension fracture area of the Suntuan Mine in the Huaibei mining area. Samples were collected before subsidence (April 2019), and after sibsidence (December 2019, July 2020). Five sampling points were randomly located before subsidence. Two typical longitudinal tension fractures were selected after subsidence, and the subsidence area was divided into three zones from the top to the bottom of the subsidence slope. Thirteen sampling points were located on both sides of each fracture. At each sampling point, one soil sample was collected every 20 cm of soil depth. Sample collection was completed in December 2019 and July 2020. Six soil indicators were monitored: water content, organic matter, fast-acting potassium, fast-acting phosphorus, total nitrogen, and total phosphorus. [Results] There were significant differences in soil moisture content, organic matter, available potassium, and total phosphorus between the two samplings in the tension fracture area (p0.05). Principal component analysis showed that the first principal components were organic matter, total nitrogen, and total phosphorus (positive), and the second principal components were water content and fast-acting potassium (negative). Based on the comprehensive nutrient evaluation-principal component score analysis, the integrated nutrient score increased with time. However, the nutrients in the tension fracture zone gradually increased from the top to the bottom of the subsidence slope. [Conclusion] Surface tension fractures were widely distributed in the coal mining subsidence area, leading to a decline in soil quality.

Background: The C-reactive protein–albumin–lymphocyte (CALLY) index is a novel inflammatory biomarker, and its association with the prognosis of coronary artery disease (CAD) after percutaneous coronary intervention (PCI) has not previously been studied. Therefore, this study aimed to investigate the effect of using the CALLY index on adverse outcomes in CAD patients undergoing PCI. Methods: From December 2016 to October 2021, we consecutively enrolled 15,250 CAD patients and performed follow-ups for primary endpoints consisting of all-cause mortality (ACM) and cardiac mortality (CM). The CALLY index was computed using the following formula: (albumin × lymphocyte)/(C-reactive protein (CRP) × 104). The average duration of the follow-up was 24 months. Results: A total of 3799 CAD patients who had undergone PCI were ultimately enrolled in the present study. The patients were divided into four groups according to the CALLY index quartiles: Q1 (≤0.69, n = 950), Q2 (0.69–2.44, n = 950), Q3 (2.44–9.52, n = 950), and Q4 (>9.52, n = 949). The low-Q1 group had a significantly higher prevalence of ACM (p < 0.001), CM (p < 0.001), major adverse cardiac events (MACEs) (p = 0.002), and major adverse cardiac and cerebrovascular events (MACCEs) (p = 0.002). Kaplan–Meier analysis revealed that a low CALLY index was significantly linked with adverse outcomes. After univariate and multivariate Cox regression analysis, the risk of ACM, CM, MACEs, and MACCEs decreased by 73.7% (adjust hazard risk [HR] = 0.263, 95% CI: 0.147–0.468, p < 0.001), 70.6% (adjust HR = 0.294, 95% CI: 0.150–0.579, p < 0. 001), 37.4% (adjust HR = 0.626, 95% CI: 0.422–0.929, p = 0.010), and 41.5% (adjust HR = 0.585, 95% CI: 0.401–0.856, p = 0.006), respectively, in the Q4 quartiles compared with the Q1 quartiles. Conclusions: This study revealed that a decreased CALLY index was associated with worse prognoses for CAD patients after PCI. The categorization of patients with a decreased CALLY index could provide valuable evidence for the risk stratification of adverse outcomes in CAD patients after PCI. Clinical Trial Registration: The details are available at http://www.chictr.org.cn (Identifier: NCT05174143).

We present a statistical study of the properties of diffuse H i in 10 nearby galaxies, comparing the H i detected by the single-dish telescope FAST (FEASTS program) and the interferometer Very Large Array (THINGS program), respectively. The THINGS observation missed H i with a median of 23% due to the short-spacing problem of interferometry and limited sensitivity. We extract the diffuse H i by subtracting the dense H i , which is obtained from the THINGS data with a uniform flux-density threshold, from the total H i detected by FAST. Among the sample, the median diffuse-H i fraction is 34%, and more diffuse H i is found in galaxies exhibiting more prominent tidal-interaction signatures. The diffuse H i we detected seems to be distributed in disk-like layers within a typical thickness of 1 kpc, different from the more halo-like diffuse H i detected around NGC 4631 in a previous study. Most of the diffuse H i is cospatial with the dense H i and has a typical column density of 10 ^17.7 –10 ^20.1 cm ^−2 . The diffuse and dense H i exhibit a similar rotational motion, but the former lags by a median of 25% in at least the inner disks, and its velocity dispersions are typically twice as high. Based on a simplified estimation of circumgalactic medium properties and assuming pressure equilibrium, the volume density of diffuse H i appears to be constant within each individual galaxy, implying its role as a cooling interface. Comparing with existing models, these results are consistent with a possible link between tidal interactions, the formation of diffuse H i , and gas accretion.

The application of titanium alloy in shipbuilding can reduce ship weight and carbon emissions. To solve the problem of titanium alloy forming, the deformation prediction of titanium alloy line heating based on a backpropagation (BP) neural network and sparrow search algorithm (SSA) was researched. Based on the thermal–elastic–plastic finite element method, the numerical calculation model of TA5 titanium alloy overlapping heating forming was established. The feasibility of the model was verified by comparing it with the numerical calculation and experiment of low-carbon steel. Considering the characteristics of the titanium alloy-forming process, 73 groups of titanium alloy-forming schemes were obtained by the Latin hypercube sampling method. The deformation data of the samples were obtained by using the numerical calculation model of titanium alloy forming. The prediction methods of titanium alloy-forming deformation based on BP, genetic algorithm–backpropagation (GA-BP), and SSA-BP were proposed. The accuracy of different neural network prediction models was analyzed. The mean absolute percentage errors (MAPEs) of BP, GA-BP, and SSA-BP in shrinkage prediction were 7.45%, 4.08%, and 2.96%, respectively. The MAPEs of BP, GA-BP, and SSA-BP in deflection prediction were 8.44%, 4.73%, and 2.64%, respectively. The goodness of fit (R2) of SSA-BP is closest to 1 among the three models. The calculation results show that SSA-BP is better than BP and GA-BP in predicting the forming deformation of titanium alloy. The maximum prediction error of SSA-BP is 4.95%, which is within the allowable range of engineering error. The SSA-BP prediction model is suitable for the rapid and accurate prediction of the deformation of titanium alloy line heating forming. The intelligent prediction model provides data support for intelligent decisions for titanium alloy forming.

In view of the importance of alkaline phosphatase (ALP) as a clinical diagnostic indicator of related diseases and physiological research, developing a reliable measurement assay with high efficiency and accuracy is of tremendous value. In this study, bifunctional carbon dots (CDs) with peroxidase-like and fluorescence properties were synthesized through a readily available solvothermal method. Peroxidase-like CDs could oxidaze colorless 1,4-phenylenediamine (PPD) to the colored oxidized product (oxPPD), which quenched the CDs' fluorescence. A multi-signal sensing system was strategically fabricated for detecting ALP for the first time, taking advantage of CDs' remarkable peroxidase-mimic activity and fluorescence properties. The limits of detection (LOD) and linear ranges for ALP was 0.034 and 0.027 U/L, 0.1 to 1.8 and 0.05 to 1.8 U/L by the colorimetric and fluorescent method, respectively. Besides, the results of hydrogel devices processed by smartphones also exhibited satisfactory results. The multi-signal strategy developed in this study provides a new impetus for designing different biosensors with bifunctional nanomaterials.

Abstract Control of the directional bounce of droplets impacting solid surfaces is crucial for many agricultural and industrial applications. However, for the universal impact process of raindrops on plant leaves, little is known about how the highly coupled and complicated fluid–structure interaction controls the postimpact motion of droplets and endows the leaves with tenacious vitality. Here, we report a leaf‐like superhydrophobic cantilever to flexibly bounce droplets with well‐defined directionality and controllability. Through theoretical modeling and three‐dimensional fluid–solid coupling simulations, we find that the flexible cantilever significantly relieves the impacting forces of raindrops to reduce droplet fragmentation and enhance water repellency. The results further uncover the scaling relations of the droplet bouncing direction with respect to Weber number and cantilever stiffness. By this technique, the seemed disorganized postimpact movements of droplets are programmable and predictable, achieving the goal of where to point and where to hit automatically. This work advances the understanding of natural droplet impact phenomena, opens a new avenue for delicately controlling liquid motion in space with soft materials, and inspires a plethora of applications like soft robots to transport materials and energies, monitor plant growth as well as predict pathogen transmission in plants.

Summary: Protein lysine crotonylation has been recently identified as a vital posttranslational modification in cellular processes, particularly through the modification of histones. We show that lysine crotonylation is an important modification of the cytoplastic and mitochondria proteins. Enzymes in glycolysis, the tricarboxylic acid (TCA) cycle, fatty acid metabolism, glutamine metabolism, glutathione metabolism, the urea cycle, one-carbon metabolism, and mitochondrial fusion/fission dynamics are found to be extensively crotonylated in pancreatic cancer cells. This modulation is mainly controlled by a pair of crotonylation writers and erasers including CBP/p300, HDAC1, and HDAC3. The dynamic crotonylation of metabolic enzymes is involved in metabolism regulation, which is linked with tumor progression. Interestingly, the activation of MTHFD1 by decrotonylation at Lys354 and Lys553 promotes the development of pancreatic cancer by increasing resistance to ferroptosis. Our study suggests that crotonylation represents a metabolic regulatory mechanism in pancreatic cancer progression.

Magnesium hydride (MgH2) is one of the most promising hydrogen storage materials for practical application due to its favorable reversibility, low cost and environmental benign; however, it suffers from high dehydrogenation temperature and slow sorption kinetics. Exploring proper catalysts with high and sustainable activity is extremely desired for substantially improving the hydrogen storage properties of MgH2. In this work, a composite catalyst with high-loading of ultrafine Ni nanoparticles (NPs) uniformly dispersed on porous hollow carbon nanospheres is developed, which shows superior catalytic activity towards the de-/hydrogenation of MgH2. With an addition of 5 wt% of the composite, which contains 90 wt% Ni NPs, the onset and peak dehydrogenation temperatures of MgH2 are lowered to 190 and 242 °C, respectively. 6.2 wt% H2 is rapidly released within 30 min at 250 °C. The amount of H2 that the dehydrogenation product can absorb at a low temperature of 150 °C in only 250 s is very close to the initial dehydrogenation value. A dehydrogenation capacity of 6.4 wt% remains after 50 cycles at a moderate cyclic regime, corresponding to a capacity retention of 94.1%. The Ni NPs are highly active, reacting with MgH2 and forming nanosized Mg2Ni/Mg2NiH4. They act as catalysts during hydrogen sorption cycling, and maintain a high dispersibility with the help of the dispersive role of the carbon substrate, leading to sustainably catalytic activity. The present work provides new insight into designing stable and highly active catalysts for promoting the (de)hydrogenation kinetics of MgH2.

Light penetration and overheating are major issues facing the application of photothermal therapy. Here, the authors develop a temperature responsive hydrogel optical waveguide for controlled delivery of light to deep tumours and demonstrate biocompatibility and temperature responsive phototherapy in vivo

Abstract Many slow‐moving landslides in the Three Gorges Reservoir (TGR) area exhibit episodic movement patterns in response to variations in the reservoir water level and seasonal rainfall. These landslides are typically characterized by pre‐existing shear zones composed of thick, clay‐rich layers that are sensitive to hydrological forcings. The residual shear strength of these shear zones is believed to control the dynamic movements of these landslides. In this article, we review the recent advances in the investigation of a large slow‐moving landslide, the Huangtupo landslide, in the TGR area. This landslide has been chosen as a benchmark for studying similar landslides in this area. This review focuses mainly on the research carried out by the authors and their collaborators over the last 5 years on topics including the landslide mechanisms and forcings, rheological behaviors and constitutive models of the landslide materials, the numerical simulation of clastic shear‐zone soils, and the effects landslide‐induced tsunamis would have on the ships in the reservoir. In addition, new perspectives and challenges for future research on slow‐moving landslides are provided.

Abstract Background Stool DNA (sDNA) tests and fecal immunochemical test (FIT) are used for the detection of colorectal cancer (CRC). Here we performed a novel evaluation using sDNA and FIT to assess their performance in CRC screening and monitoring in Hubei, China. Methods Stool samples were collected from a high-risk population in Hubei, China (n = 359). sDNA tests and FIT were performed to test for KRAS mutations, NDRG4 and BMP3 methylation, and check hemoglobin levels. The methylation in BMP3 and NDRG4 genes was detected by TaqMan PCR method from human fecal samples. KRAS gene mutation in human fecal DNA was tested using TaqMan probe and amplification-refractory mutation system method. The colloid gold method was used for detection of hemoglobin in fecal samples. Finally, a novel evaluation by software was used to calculate the comprehensive value of the combined results for CRC detection and monitoring. Results The sensitivity and specificity of the novel evaluation for early CRC (stage I and II), advanced adenoma (AA), and non-colon cancer neoplasm (NA) detection were 95.45% and 81.6%, 29.63% and 75.9%, and 23.08% and 75.17%, respectively. The receiver operating characteristic (ROC) curves of the combined value for the above diseases were 0.945 ± 0.015, 0.543 ± 0.055, and 0.547 ± 0.038, respectively. The levels of the novel evaluation were not significantly associated with the pathology and stage (P > 0.05). In 20 out of 22 CRC patients, the novel evaluation of sDNA and FIT had decreased below threshold (

Abstract Background Induced pluripotent stem cells (iPSCs) have the potential to promote wound healing; however, their adhesion to the extracellular matrix (ECM) might decrease iPSC migration, thereby limiting their therapeutic potential. Integrin β1 (Itgb1) is the major integrin subunit that mediates iPSC-ECM adhesion, suggesting that knocking out Itgb1 might be an effective method for enhancing the therapeutic efficacy of iPSCs. Methods We knocked out Itgb1 in mouse iPSCs and evaluated its effects on the therapeutic potential of topically applied iPSCs, as well as their underlying in vivo and in vitro mechanisms. Results The Itgb1-knockout (Itgb1-KO) did not change iPSC pluripotency, function, or survival in the absence of embedding in an ECM gel but did accelerate wound healing, angiogenesis, blood perfusion, and survival in skin-wound lesions. However, embedding in an ECM gel inhibited the in vivo effects of wild-type iPSCs but not those of Itgb1-knockout iPSCs. Additionally, in vitro results showed that Itgb1-knockout decreased iPSC-ECM adhesion while increasing ECM-crossing migration. Moreover, ECM coating on the culture surface did not change cell survival, regardless of Itgb1 status; however, the in vivo and in vitro functions of both Itgb1-knockout and wild-type iPSCs were not affected by the presence of agarose gel, which does not contain integrin-binding sites. Knockout of Integrin α4 (Itga4) did not change the above-mentioned cellular and therapeutic functions of iPSCs. Conclusions Itgb1-knockout increased iPSCs migration and the wound-healing-promoting effect of topically applied iPSCs. These findings suggest the inhibition of Itgb1 expression is a possible strategy for increasing the efficacy of iPSC therapies.

Chen et al. report on a renal UTX-phosphoglycerate dehydrogenase axis that regulates serine secretion to affect lipid metabolism in the kidney and liver upon over-nutrition, suggesting potential treatment targets for obesity-related diseases.

Abstract A simple method was proposed to activate alkaline Cu(OH)2 with an acidic ionomer, Nafion, to regulate its surface microenvironment, including hydrophobicity and local basicity. In particular, the direct complete neutralization reaction between Cu(OH)2 and Nafion in aqueous solution induces the exposing of vast anions which can exclude the in‐situ‐formed hydroxides and raise the local basicity. Remarkably, the optimal Nafion‐activated Cu(OH)2‐derived Cu can efficiently suppress the hydrogen evolution reaction (HER) and improve the selectivity for multi‐carbon products in the CO2 electroreduction reaction (eCO2RR). The H2 Faradaic efficiency (FE) decreased to 11% at a current density of 300 mA/cm2 (−0.76 V vs. RHE) in a flow cell, while the bare one with H2 had an FE of 40%. The total eCO2RR FE reaches as high as 83%, along with an evidently increased C2H4 FE of 44% as compared with the bare one (24%), and good stability (8000 s), surpassing that of most of the reported Cu(OH)2‐derived Cu. The experimental and theoretical results both show that the strong hydrophobicity and high local basicity jointly boosted the eCO2RR as acquired by felicitously introducing ionomer on the Cu(OH)2‐derived Cu surface.

To accurately unwrap the high-order orbital angular momentum (OAM) for multiplexed vortex beams is a challenge. In this work, over ±160 order OAM topological charges have been unwrapped in multiplexed optical links. Optical imaging based discrepancy identification enables the multiplexed OAM modes separating in physics, and the intelligent pattern recognition further promotes its unwrapping in numerical domain. Particularly, the combination of annular phase grating and auxiliary beams features compound spiral stripes, which paves the way for optical intensity recognition with low-complexity and high-commonality. Moreover, the spiral direction characterizes the symbol of the OAM states, which dramatically broadens the amount of multiplexed links. Here, optical separating means assisted by intelligent pattern recognition opens up a new route to high-speed and large-capacity optical communication, which may shed new light on 6G application.

Background: Intratumoral hypoxia is widely associated with the development of malignancy, treatment resistance, and worse prognoses. The global influence of hypoxia-related genes (HRGs) on prognostic significance, tumor microenvironment characteristics, and therapeutic response is unclear in patients with non-small cell lung cancer (NSCLC).Method: RNA-seq and clinical data for NSCLC patients were derived from The Cancer Genome Atlas (TCGA) database, and a group of HRGs was obtained from the MSigDB. The differentially expressed HRGs were determined using the limma package; prognostic HRGs were identified via univariate Cox regression. Using the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression, an optimized prognostic model consisting of nine HRGs was constructed. The prognostic model’s capacity was evaluated by Kaplan‒Meier survival curve analysis and receiver operating characteristic (ROC) curve analysis in the TCGA (training set) and GEO (validation set) cohorts. Moreover, a potential biological pathway and immune infiltration differences were explained.Results: A prognostic model containing nine HRGs (STC2, ALDOA, MIF, LDHA, EXT1, PGM2, ENO3, INHA, and RORA) was developed. NSCLC patients were separated into two risk categories according to the risk score generated by the hypoxia model. The model-based risk score had better predictive power than the clinicopathological method. Patients in the high-risk category had poor recurrence-free survival in the TCGA (HR: 1.426; 95% CI: 0.997–2.042; p = 0.046) and GEO (HR: 2.4; 95% CI: 1.7–3.2; p < 0.0001) cohorts. The overall survival of the high-risk category was also inferior to that of the low-risk category in the TCGA (HR: 1.8; 95% CI: 1.5–2.2; p < 0.0001) and GEO (HR: 1.8; 95% CI: 1.4–2.3; p < 0.0001) cohorts. Additionally, we discovered a notable distinction in the enrichment of immune-related pathways, immune cell abundance, and immune checkpoint gene expression between the two subcategories.Conclusion: The proposed 9-HRG signature is a promising indicator for predicting NSCLC patient prognosis and may be potentially applicable in checkpoint therapy efficiency prediction.

Summary: Droplets directionally bouncing off moving superhydrophobic solid surfaces are universal in nature and are crucial in many biological, sustainable, environmental, and engineering applications. However, their underlying physics and regulation strategies remain relatively unknown. This paper demonstrates that the maximum directional acceleration of a post-impact droplet mainly occurs in the spreading stage and that the orientational velocity of the droplet mainly originates in the early impingement process. Furthermore, it clarifies the underlying physics based on momentum transfer process imposed by the boundary layer of impacts and proposes a strategy for regulating the directional droplet velocity using a comprehensive formula. Finally, it shows that directional bouncing reduces the flight momentum of a small flying device by 10%–22%, and the experimental values agree closely with the predicted values. This study reveals the droplet bounce orientation mechanism imposed by moving substrates, provides manipulation methods, and makes positive and meaningful discussions of practical applications.

Using numerical software to establish a three-dimensional geological model of shield tunneling through fault fracture zones, considering the synchronous grouting effect at the shield tail, the disturbance of various geotechnical structures in the fault fracture zone under deep burial and high water pressure conditions is studied. According to the comparison between the numerical model analysis results and the on-site inspection results of the entire process of Shiziyang B3 section, synchronous grouting at the shield tail is the main reason for the changes in soil and water pressure in the fault fracture zone area. The soil and water pressure changes strongly during shield tunneling, and the maximum excess pore pressure value occurs when the shield tail passes. When the shield tunneling machine is far away, the soil and water stress shows a downward trend. The impact of synchronous grouting decreases with the increase in tunneling distance. Due to the difference in permeability, the variation law of pore pressure in the fault fracture zone is significantly different from the original rock, leading to a faster increase in pore pressure in the fracture zone area and a wider range of influence.

Aerobic composting is an effective method of resource treatment for agricultural and forestry solid waste; however, while wheat straw is usually used as a conditioner and is not the main body as in aerobic composting, wheat straw is abundant in annual production, and fertilization is one of the main ways of resource utilization of wheat straw, how to use wheat straw as the main body of aerobic composting for efficient treatment is, therefore, a meaningful research direction. In this paper, to achieve the efficient and economic resource utilization of wheat straw and livestock manure, aerobic composting was carried out with wheat straw as the main body, and pig manure and cow manure were mixed with wheat straw crops at ratios of 20%, 30%, and 40%, respectively, for barrel suspension composting. The changes in pH, EC, NH4+-N, NO3−-N, TN, TP, organic matter and seed germination index, and shoot length inhibition rate before and after composting were compared between treatment groups using different material ratios in the aerobic composting process. The changes in the physicochemical properties and nutrient elements of compost products were studied. The results show that the co-composting of livestock manure and wheat straw can promote the decomposition of the pile, and the addition of 40% cow manure and 30% pig manure has the best effect in promoting decay. In contrast, the addition of excessive pig manure inhibits the decomposition of the pile. Organic matter degradation in the treatment groups using cow manure was more effective than in those using pig manure, and the best results were obtained with 40% cow manure. The pile was alkaline at the end of each treatment, and the wheat straw compost treated with 40% cow manure had the best nitrogen and phosphorus retention. The wheat straw compost treated with 40% cow manure had the highest integrated degree of decomposition, which promoted the deterioration of the pile and provided a research basis for the use of wheat straw as an efficient resource.