Search

Abstract Background Sublobar resection (wedge resection and segmentectomy) has been established as an oncologically equivalent option to lobectomy for early‐stage patients with non‐small cell lung cancer (NSCLC) ≤ 2 cm. However, the optimal approach of sublobar resection remains subject to debate. In the present study we aimed to compare the oncological outcomes of wedge resection and segmentectomy in these patients. Methods We identified patients with pT1a‐bN0M0 NSCLC who underwent wedge resection and segmentectomy from the Surveillance, Epidemiology, and End Results database between 2010 and 2020. A Cox regression model and propensity‐score matching (PSM) analysis were used. Overall survival (OS) and lung cancer‐specific survival (LCSS) were compared using the Kaplan–Meier method. Results A total of 4190 patients met our selection criteria, including wedge resection in 3137 and segmentectomy in 1053. Patients undergoing wedge resection were less likely to have total lymph nodes resected (4 vs. 7, p

In situ monitoring of bone regeneration enables timely diagnosis and intervention by acquiring vital biological parameters. However, an existing gap exists in the availability of effective methodologies for continuous and dynamic monitoring of the bone tissue regeneration process, encompassing the concurrent visualization of bone formation and implant degradation. Here, we present an integrated scaffold designed to facilitate real-time monitoring of both bone formation and implant degradation during the repair of bone defects. Laponite (Lap), CyP-loaded mesoporous silica (CyP@MSNs) and ultrasmall superparamagnetic iron oxide nanoparticles (USPIO@SiO2) were incorporated into a bioink containing bone marrow mesenchymal stem cells (BMSCs) to fabricate functional scaffolds denoted as C@M/GLU using 3D bioprinting technology. In both in vivo and in vitro experiments, the composite scaffold has demonstrated a significant enhancement of bone regeneration through the controlled release of silicon (Si) and magnesium (Mg) ions. Employing near-infrared fluorescence (NIR-FL) imaging, the composite scaffold facilitates the monitoring of alkaline phosphate (ALP) expression, providing an accurate reflection of the scaffold's initial osteogenic activity. Meanwhile, the degradation of scaffolds was monitored by tracking the changes in the magnetic resonance (MR) signals at various time points. These findings indicate that the designed scaffold holds potential as an in situ bone implant for combined visualization of osteogenesis and implant degradation throughout the bone repair process.

Abstract Despite potential in high-resolution and low-cost displays and lighting, multi-doping structures and low concentrations (

Peripheral nervous system (PNS) injuries often lead to significant sensory and motor impairments. Traditional artificial nerve conduits, lacking anisotropic structures, have been associated with prolonged repair time and failures in nerve regeneration. This study aimed to address these challenges by developing a novel approach for rapid repair of peripheral nerve injuries (PNI). A 3D oriented fibers scaffold featuring distinct radial (RFs) and longitudinal (LFs) fibers orientations was engineered using coaxial electrospinning and gas directional foaming techniques. This scaffold was then integrated with a shape memory conduit to form a directional multi-channel nerve conduit with micro/nanostructures. The results revealed that the grooved surface of the fibers significantly improved cellular directional guidance, effectively facilitating the migration of SCs from the periphery towards the center and from the base to the apex of the scaffold. In a rat model with a 10 mm nerve defect, the ND-PLATMC/LF ND-PCL scaffold significantly enhanced nerve regeneration and motor function recovery within 4 weeks. These results suggest the potential of this innovative scaffold for efficient repair of the nerve injuries.

Abstract Constructing nanolaminate membranes made of two-dimensional graphene oxide nanosheets has gained enormous interest in recent decades. However, a key challenge facing current graphene-based membranes is their poor rejection for monovalent salts due to the swelling-induced weak nanoconfinement and the transmembrane co-transport of anions and cations. Herein, we propose a strategy of electrostatic-induced ion-confined partitioning in a reduced graphene oxide membrane for breaking the correlation of anions and cations to suppress anion-cation co-transport, substantially improving the desalination performance. The membrane demonstrates a rejection of 95.5% for NaCl with a water permeance of 48.6 L m−2 h−1 bar−1 in pressure-driven process, and it also exhibits a salt rejection of 99.7% and a water flux of 47.0 L m−2 h−1 under osmosis-driven condition, outperforming the performance of reported graphene-based membranes. The simulation and calculation results unveil that the strong electrostatic attraction of membrane forces the hydrated Na+ to undergo dehydration and be exclusively confined in the nanochannels, strengthening the intra-nanochannel anion/cation partitioning, which refrains from the dynamical anion-cation correlations and thereby prevents anions and cations from co-transporting through the membrane. This study provides guidance for designing advanced desalination membranes and inspires the future development of membrane-based separation technologies.

Abstract Background The surgical outcomes for younger patients with non‐small cell lung cancer (NSCLC) remain uncertain. The aim of this study was to investigate the clinical features long‐term survival outcomes in younger individuals with NSCLC following surgery. Methods We queried the Surveillance, Epidemiology, and End Results database from 2010 to 2017, selecting all pathologically confirmed NSCLC cases that underwent cancer‐directed surgery. Younger patients were defined as those aged 18–50 years, while older patients were 51–80 years. Propensity score matching (PSM) was implemented to mitigate selection bias. Overall survival (OS) and lung cancer‐specific survival (LCSS) were compared using the Kaplan–Meier method. Results Among the 33 586 treated surgically patients, 2223 (6.6%) were young. Compared to the older group, younger patients had a higher frequency of female gender, non‐white ethnicity, carcinoid tumors, stage IV disease, pneumonectomy, and postoperative adjuvant therapies. The 5‐year OS rates were significantly higher for younger patients (79.3% vs. 62.0%; p

Objective: To explore a precise association between tumor location and lymph node (LN) biopsy algorithm in uterine confined endometrial cancer (EC). Materials and methods: Patients with EC treated in the Department of Obstetrics and Gynecology, South Branch of Fujian Provincial Hospital were included in this observational retrospective study. Based on the procedure of treatment, patients were separated to stage I (2015.07–2019.09) and stage II (2019.09–2021.9). In each stage, patients were separated to high and low-risk group by the predicted results. Patients in the high-risk group received systematic lymphadenectomy in stage I and sentinel lymph node (SLN) dissection in stage II. The efficiency of lymph node metastasis (LNM) detection rates was compared between stage I and stage II cases. Precise lymph node biopsy algorithm was also constructed based on the outcomes of stage II. Results: Overall, 43 patients, 28 in stage I and 15 in stage II, were included in the study. No recurrence or death cases had been found within follow-up terms. Based on the difference in the detection efficiency of LNM (p > 0.05), there was no difference between two stages. Thus, systematic lymphadenectomy and SLN biopsy provided similar success rates. The location of tumor site was also important for deciding whether pelvic or para-aortic SLN should be sampled for LNM. Conclusions: Precise SLN biopsy for EC confined to the uterus showed comparable LNM detection rate as systematic lymphadenectomy. EC location may be used to determine whether pelvic or para-aortic SLN sampling should be conducted for treatment.

Abstract Organic ultralong room-temperature phosphorescence (RTP) usually emerges instantly and immediately decays after excitation removal. Here we report a new delayed RTP that is postponed by dozens of milliseconds after excitation removal and decays in two steps including an initial increase in intensity followed by subsequent decrease in intensity. The delayed RTP is achieved through introduction of phosphines into carbazole emitters. In contrast to the rapid energy transfer from single-molecular triplet states (T1) to stabilized triplet states (Tn*) of instant RTP systems, phosphine groups insert their intermediate states (TM) between carbazole-originated T1 and Tn* of carbazole-phosphine hybrids. In addition to markedly increasing emission lifetimes by ten folds, since TM → Tn* transition require >30 milliseconds, RTP is thereby postponed by dozens of milliseconds. The emission character of carbazole-phosphine hybrids can be used to reveal information through combining instant and delayed RTP, realizing multi-level time resolution for advanced information, biological and optoelectronic applications.

The smoking rate is high in patients with schizophrenia. Brain stimulation targeting conventional brain circuits associated with nicotine addiction has also yielded mixed results. We aimed to identify alternative circuitries associated with nicotine addiction in both the general population and schizophrenia, and then test whether modulation of such circuitries may alter nicotine addiction behaviors in schizophrenia. In Study I of 40 schizophrenia smokers and 51 non-psychiatric smokers, cross-sectional neuroimaging analysis identified resting state functional connectivity (rsFC) between the dorsomedial prefrontal cortex (dmPFC) and multiple extended amygdala regions to be most robustly associated with nicotine addiction severity in healthy controls and schizophrenia patients (p = 0.006 to 0.07). In Study II with another 30 patient smokers, a proof-of-concept, patient- and rater-blind, randomized, sham-controlled rTMS design was used to test whether targeting the newly identified dmPFC location may causally enhance the rsFC and reduce nicotine addiction in schizophrenia. Although significant interactions were not observed, exploratory analyses showed that this dmPFC–extended amygdala rsFC was enhanced by 4-week active 10Hz rTMS (p = 0.05) compared to baseline; the severity of nicotine addiction showed trends of reduction after 3 and 4 weeks (p ≤ 0.05) of active rTMS compared to sham; Increased rsFC by active rTMS predicted reduction of cigarettes/day (R = −0.56, p = 0.025 uncorrected) and morning smoking severity (R = −0.59, p = 0.016 uncorrected). These results suggest that the dmPFC–extended amygdala circuit may be linked to nicotine addiction in schizophrenia and healthy individuals, and future efforts targeting its underlying pathophysiological mechanisms may yield more effective treatment for nicotine addiction.

BackgroundBreast cancer, one of the most prevalent malignancies among women worldwide, has rising incidence rates. Physical activity, particularly exercise, has emerged as a significant modifier of cancer prognosis, influencing both tumor biology and patient outcomes.MethodsIn this study, we utilized a murine breast cancer model, dividing mice into a control group and an exercise group; the latter underwent 21 days of voluntary running. We conducted RNA sequencing, bioinformatics analysis, pan-cancer analysis, and cellular experiments to investigate the underlying mechanisms influenced by exercise.ResultsExercise led to a significant reduction in tumor size and weight. Post-exercise mRNA sequencing indicated a notable upregulation of THSD7B in the exercised mice, with significant alterations observed in pathways such as MicroRNAs in cancers and the Calcium signaling pathway. In a broader cancer context, THSD7B showed considerable expression variability, being significantly downregulated in several cancers, correlating with positive prognostic outcomes in PRAD, LAML, KIRC, and GBM and highlighting its potential role as a prognostic marker and therapeutic target. THSD7B expression was also negatively associated with processes of breast cancer cell proliferation, migration, and invasion.ConclusionThis study underscores the dual role of exercise in modulating gene expression relevant to tumor growth and highlights the potential of THSD7B as a therapeutic target in cancer. Future research should further explore the specific mechanisms by which exercise and THSD7B influence cancer progression and develop immunotherapy-enhanced strategies to change patient outcomes in clinical settings.

Summary: Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, with the highest single-cause mortality. Monocarboxylate transporter 4 (Mct4) transports intracellular lactate outside, but its role in regulating host immune response against Mtb infection remains unknown. Mct4 expression was upregulated in Mtb-infected macrophages and in patients with TB. Mct4 silencing/deficiency significantly decreased Mtb survival in macrophages and in lungs and spleens of mice, while Mct4 overexpression facilitated Mtb survival in macrophages. Furthermore, Mct4 promoted intracellular lactate transport, nuclear factor κB (NF-κB) p65 activation, and interleukin-10 (IL-10) production upon Mtb infection. Mechanistically, IL-10 silencing and IL-10-neutralizing antibody blocked Mct4 overexpressing increased Mtb survival. Replenishing lactate and NF-κB p65 inhibitor JSH23 treatment could inhibit Mct4 overexpressing increased NF-κB p65 activation, IL-10 production, and Mtb survival in macrophages. This study demonstrates that Mct4 promotes Mtb survival through restricting intracellular lactate accumulation to promote NF-κB p65-mediated IL-10 production and suggests Mct4-NF-κB p65-IL-10 axis a potential target for TB treatment.

BackgroundBreast cancer ranks as one of the most prevalent malignancies among women globally, with increasing incidence rates. Physical activity, particularly exercise, has emerged as a potentially significant modifier of cancer prognosis, influencing tumor biology and patient outcomes.MethodsUsing a murine breast cancer model, we established a control and an exercise group, where the latter was subjected to 21 days of voluntary running. RNA Sequencing, bioinformatics analysis, pan-cancer analysis, and cell experiments were performed to validate the underlying mechanisms.ResultsWe observed that exercise significantly reduced tumor size and weight, without notable changes in body weight, suggesting that physical activity can modulate tumor dynamics. mRNA sequencing post-exercise revealed substantial downregulation of CD300E in the exercise group, accompanied by alterations in critical pathways such as MicroRNAs in cancers and the Calcium signaling pathway. Expanding our analysis to a broader cancer spectrum, CD300E demonstrated significant expression variability across multiple cancer types, with pronounced upregulation in myeloma, ovarian, lung, and colorectal cancers. This upregulation was correlated with poorer prognostic outcomes, emphasizing CD300E’s potential role as a prognostic marker and therapeutic target. Moreover, CD300E expression was associated with cancer cell proliferation and apoptosis.ConclusionThe study highlights the dual role of exercise in modulating gene expression relevant to tumor growth and the potential of CD300E as a target in cancer therapeutics. Further research is encouraged to explore the mechanisms by which exercise and CD300E influence cancer progression and to develop targeted strategies that could enhance patient outcomes in clinical settings.

This article aims to address the issues of low cultivation density and high labor intensity of manual water exchange in existing scallop seedling ponds, an upwelling recirculating water system for scallop larval cultivation is designed. EDEM-Fluent coupled model was used to simulate the movement of scallop larvae in the culture cone in order to guarantee the uniform distribution of larvae in the cultivation device. Design-Expert software was utilized to investigate the impact of the bottom cone angle(θ), the column height/cone height ratio(n) and the inflow velocity(v) on the variation coefficients of the axial and radial distributions of D-shaped larvae within the culture cone. The results indicated that θ = 108.97° and n = 1.8 represent the ideal structural parameters for the culture cone. The further investigation of the culture cones prototype was conducted to examine the impact of the inlet deflector angle (α), cultivation density (τ), and inflow velocity (v) on its performance. θ=108.97°, n=1.8, v=0.19m/s, α=60.94°, and τ=110pcs/ml were found to be the ideal combination of parameters, in this scenario, the D-shaped larvae’s radial distributions’ coefficients of variation is 22.13%, the error between the experimental and simulation results is 4.41%. Research has shown that EDEM-Fluent based simulation analysis methods can be used for the design and parameter optimization of upwelling recirculating water scallop larval cultivation system, this paper can provide a reference for the design of an upwelling recirculating water scallop larval cultivation system.

Abstract The unique 1D crystal structure of Antimony Triselenide (Sb2Se3) offers notable potential for use in flexible, lightweight devices due to its excellent bending characteristics. However, fabricating high‐efficiency flexible Sb2Se3 solar cells is challenging, primarily due to the suboptimal contact interface between the embedded Sb2Se3 layer and the molybdenum back‐contact, compounded by complex intrinsic defects. This study introduces a novel Molybdenum Trioxide (MoO3) interlayer to address the back contact interface issues in flexible Sb2Se3 devices. Further investigations indicate that incorporating a MoO3 interlayer not only enhances the crystalline quality but also promotes a favorable [hk1] growth orientation in the Sb2Se3 absorber layer. It also reduces the barrier height at the back contact interface and effectively passivates harmful defects. As a result, the flexible Sb2Se3 solar cell, featuring a Mo‐foil/Mo/MoO3/Sb2Se3/CdS/ITO/Ag substrate structure, demonstrates exceptional flexibility and durability, enduring large bending radii and multiple bending cycles while achieving an impressive efficiency of 8.23%. This research offers a straightforward approach to enhancing the performance of flexible Sb2Se3 devices, thereby expanding their application scope in the field of photovoltaics.

Abstract Climate warming affects global livestock productivity. The meat yield from cattle farming (cattle meat per animal) represents livestock productivity at the individual level. However, the impact of warming on cattle meat yield at a global scale is not well understood. In this study, we combine country-level data on the annual meat yield from cattle farming and socioeconomic data from 1961 to 2020 with climate projections from General Circulation Models. The findings show that cattle meat yield increases as temperatures rise from low to medium and then decreases when annual average temperatures exceed 7 °C; this repose is pronounced in the grassland-based livestock system. Further, we show that warming creates unequal impacts between high- and low-income countries due to the divergent baseline temperature conditions. Future warming aggravates these unequal burdens between countries, with the most pronounced effects observed under the upper-middle emissions scenario.

Abstract Background Anxiety and depression can influence adherence to Pre-exposure Prophylaxis (PrEP). However, there is limited research on the temporal dynamics of anxiety and depression among men who have sex with men (MSM) using PrEP. Methods From December 2018 to November 2020, we administered the Hospital Anxiety and Depression Scale (HADS) to participants in the China Real-World Oral Intake of PrEP (CROPrEP) to measure their anxiety and depression levels. The group-based trajectory model (GBTM) depicted the dynamic changes of anxiety and depression scores over time. Results A total of 1023 MSM were included, with 4523 follow-up assessments. The GBTM categorized the trajectories into three distinct patterns: consistently low (54.8% for anxiety, 60.7% for depression), consistently moderate (39.3% for anxiety, 31.4% for depression), and high but bell-shaped (5.9% for anxiety, 7.9% for depression). Higher anxiety levels were associated with being aged 18–30 years old, earning less than US$619 per month, female-identifying, adopting the bottom sexual role with men, and having two or more anal sex partners in the past three months; similarly, higher depression levels correlated with a monthly income under US$619, female-identifying, sexual behavior as bottom and a positive syphilis at baseline. PrEP adherence was notably lower in the high but bell-shaped anxiety and depression group compared to the other groups, particularly at the 12th-month follow-up. Conclusions Close monitoring of anxiety and depression levels in MSM on PrEP is crucial. Provision of targeted mental health support is essential to enhance PrEP effectiveness.

The DC microgrid with energy storage cells has strong stability, simple control, and a convenient power supply for DC loads, increasingly becoming the grid-connected structure of distributed generation systems. This paper presents an isolated high voltage gain soft-switching dc-dc converter suitable for DC microgrid applications. The converter comprises a dual-switch quasi-z-source network, multiplier voltage cell, and transformer. It has advantages such as high voltage gain, zero voltage switching (ZVS) of switches, zero voltage zero current switching (ZVZCS) turn-on and turn-off of diodes, and low input ripple current. The converter can achieve high voltage gain with an appropriate duty cycle and transformer turns ratio, reducing leakage inductance of transformer, which decreases the power loss and voltage spike of switch. Soft-switching of active devices increases the efficiency and decreases the output voltage ripples of the converter. The steady-state characteristics of the converter, voltage and current stress of components, the efficiency of the converter, and the selection of converter parameters are analyzed in detail. Finally, a 200 W experimental prototype is built in the laboratory for experimental verification, and the experimental results are consistent with the theoretical analysis.

Abstract Background Risk stratification and personalized care are crucial in managing osteosarcoma due to its complexity and heterogeneity. However, current prognostic prediction using clinical variables has limited accuracy. Thus, this study aimed to explore potential molecular biomarkers to improve prognostic assessment. Methods High-throughput inhibitor screening of 150 compounds with broad targeting properties was performed and indicated a direction towards super-enhancers (SEs). Bulk RNA-seq, scRNA-seq, and immunohistochemistry (IHC) were used to investigate SE-associated gene expression profiles in osteosarcoma cells and patient tissue specimens. Data of 212 osteosarcoma patients who received standard treatment were collected and randomized into training and validation groups for retrospective analysis. Prognostic signatures and nomograms for overall survival (OS) and lung metastasis-free survival (LMFS) were developed using Cox regression analyses. The discriminatory power, calibration, and clinical value of nomograms were evaluated. Results High-throughput inhibitor screening showed that SEs significantly contribute to the oncogenic transcriptional output in osteosarcoma. Based on this finding, focus was given to 10 SE-associated genes with distinct characteristics and potential oncogenic function. With multi-omics approaches, the hyperexpression of these genes was observed in tumor cell subclusters of patient specimens, which were consistently correlated with poor outcomes and rapid metastasis, and the majority of these identified SE-associated genes were confirmed as independent risk factors for poor outcomes. Two molecular signatures were then developed to predict survival and occurrence of lung metastasis: the SE-derived OS-signature (comprising LACTB, CEP55, SRSF3, TCF7L2, and FOXP1) and the SE-derived LMFS-signature (comprising SRSF3, TCF7L2, FOXP1, and APOLD1). Both signatures significantly improved prognostic accuracy beyond conventional clinical factors. Conclusions Oncogenic transcription driven by SEs exhibit strong associations with osteosarcoma outcomes. The SE-derived signatures developed in this study hold promise as prognostic biomarkers for predicting OS and LMFS in patients undergoing standard treatments. Integrative prognostic models that combine conventional clinical factors with these SE-derived signatures demonstrate substantially improved accuracy, and have the potential to facilitate patient counseling and individualized management.

Abstract Backgrounds The hypoxia-responsive state of cancer is a complex pathophysiological process involving numerous genes playing different roles. Due to the rapid proliferation of cancer cells and chaotic angiogenesis, the clinical features of hypoxia-responsive states are not yet clear in patients with ovarian cancer. Methods Based on the RNA expression levels of 14 hypoxic markers, our study screened out hypoxia-related genes and construct a hypoxic score pattern to quantify the hypoxia-responsive states of a single tumor. Combining clinical prognosis, tumor mutation burden, microsatellite instability, the expression level of the immune checkpoint, IC50, and other indicators to evaluate the impact of different hypoxia-responsive states on clinical prognosis and therapeutic sensitivity. Results Our study identified a subgroup with an active hypoxia-responsive state and they have a worse clinical prognosis but exhibit higher immunogenicity and higher sensitivity to immunotherapy. Conclusions This work revealed that hypoxia-responsive states played an important role in formation of tumor immunogenicity. Evaluating the hypoxia-responsive state will contribute to guiding more effective immunotherapy strategies.

Abstract Exploring new near-room-temperature thermoelectric materials is significant for replacing current high-cost Bi2Te3. This study highlights the potential of Ag2Se for wearable thermoelectric electronics, addressing the trade-off between performance and flexibility. A record-high ZT of 1.27 at 363 K is achieved in Ag2Se-based thin films with 3.2 at.% Te doping on Se sites, realized by a new concept of doping-induced orientation engineering. We reveal that Te-doping enhances film uniformity and (00l)-orientation and in turn carrier mobility by reducing the (00l) formation energy, confirmed by solid computational and experimental evidence. The doping simultaneously widens the bandgap, resulting in improved Seebeck coefficients and high power factors, and introduces TeSe point defects to effectively reduce the lattice thermal conductivity. A protective organic-polymer-based composite layer enhances film flexibility, and a rationally designed flexible thermoelectric device achieves an output power density of 1.5 mW cm−2 for wearable power generation under a 20 K temperature difference.

Background & Aims: Apolipoprotein A-1 (ApoA-1), the main apolipoprotein of high-density lipoprotein, has been well studied in the area of lipid metabolism and cardiovascular diseases. In this project, we clarify the function and mechanism of ApoA-1 in liver regeneration. Methods: Seventy percent of partial hepatectomy was applied in male ApoA-1 knockout mice and wild-type mice to investigate the effects of ApoA-1 on liver regeneration. D-4F (ApoA-1 mimetic peptide), autophagy activator, and AMPK activator were used to explore the mechanism of ApoA-1 on liver regeneration. Results: We demonstrated that ApoA-1 levels were highly expressed during the early stage of liver regeneration. ApoA-1 deficiency greatly impaired liver regeneration after hepatectomy. Meanwhile, we found that ApoA-1 deficiency inhibited autophagy during liver regeneration. The activation of autophagy protected against ApoA-1 deficiency in inhibiting liver regeneration. Furthermore, ApoA-1 deficiency impaired autophagy through AMPK-ULK1 pathway, and AMPK activation significantly improved liver regeneration. The administration of D-4F could accelerated liver regeneration after hepatectomy. Conclusions: These findings suggested that ApoA-1 played an essential role in liver regeneration through promoting autophagy in hepatocytes via AMPK-ULK1 pathway. Our findings enrich the understanding of the underlying mechanism of liver regeneration and provide a potential therapeutic strategy for liver injury.

Abstract Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity, safeguarding receptor activation, and facilitating amplification of signal transduction across the cellular membrane. However, cell-surface antigen-induced multimerization (dubbed AIM herein) has not yet been consciously leveraged in chimeric antigen receptor (CAR) engineering for enriching T cell-based therapies. We co-developed ciltacabtagene autoleucel (cilta-cel), whose CAR incorporates two B-cell maturation antigen (BCMA)-targeted nanobodies in tandem, for treating multiple myeloma. Here we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated cytotoxicity. Crystallographic analysis of BCMA–nanobody complexes revealed atomic details of antigen–antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in solution. BCMA-induced nanobody CAR multimerization enhanced cytotoxicity, alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release, towards myeloma-derived cells. Our results provide a framework for contemplating the AIM approach in designing next-generation CARs.

Starting from the consideration of the structure of human milk fat globule (MFG), this study aimed to investigate the effects of ultrasonic treatment on milk fat globule membrane (MFGM) and soy lecithin (SL) complexes and their role in mimicking human MFG emulsions. Ultrasonic power significantly affected the structure of the MFGM-SL complex, further promoting the unfolding of the molecular structure of the protein, and then increased solubility and surface hydrophobicity. Furthermore, the microstructure of mimicking MFG emulsions without sonication was unevenly distributed, and the average droplet diameter was large. After ultrasonic treatment, the droplets of the emulsion were more uniformly dispersed, the particle size was smaller, and the emulsification properties and stability were improved to varying degrees. Especially when the ultrasonic power was 300 W, the mimicking MFG emulsion had the highest encapsulation rate and emulsion activity index and emulsion stability index were increased by 60.88 % and 117.74 %, respectively. From the microstructure, it was observed that the spherical droplets of the mimicking MFG emulsion after appropriate ultrasonic treatment remain well separated without obvious flocculation. This study can provide a reference for the screening of milk fat globules mimicking membrane materials and the further utilization and development of ultrasound in infant formula.

Background: Myocardial infarction (MI) remains one of the major causes of high morbidity and mortality worldwide. Danggui Buxue Decoction (DBD)—an ancient Chinese herbal decoction—has been used to prevent coronary heart disease, which was called “chest palsy” in ancient clinics. However, the mechanism of DBD in the treatment of MI remains unclear. The aim of this study was to explore the effect and mechanism of DBD on MI by combining network pharmacology with in vivo experiments. Materials and methods: First, public databases were used to identify the key active chemicals and possible targets of DBD. The MI targets were obtained from the Therapeutic Target Database, and the function of the target genes in relation to linked pathways was investigated. Subsequently, Cytoscape software was used to build a target-signaling pathway network. Finally, the efficacy of DBD therapy on MI was validated using in vivo investigations combined with molecular docking. Results: In traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), 27 bioactive compounds were screened from DBD. A total of 213 common targets were obtained, including 507 DBD targets and 2566 MI targets. Enrichment analysis suggests that PI3K/AKT is a potential signaling pathway for DBD-based protection. Immunofluorescence and protein blotting confirmed PI3K/AKT1, ERK2, and CASPASE-9 as the target proteins. Molecular docking analysis showed that quercetin, kaempferol, isoflavanones, isorhamnetin, hederagenin, and formononetin had high binding affinity to AKT1, ERK2, and CASPASE-9. Conclusions: This study demonstrated that the therapeutic benefit of DBD on MI may be mediated via target proteins in the PI3K/AKT pathway, such as AKT1, ERK2, and CASPASE-9. Our study data can help to provide ideas and identify new treatment targets for MI.

Soil pH is important for influencing soil properties. High input of nitrogen (N) fertilizers and irrigation water has accelerated the soil acidification in plastic-shed greenhouses. However, little is known about the dynamics of soil pH buffering system, especially the base cations, and its response mechanisms under different N management practices. In this study, we investigated the responses of soil Ca2+ and Mg2+ leaching loss to nitrate leaching under different N application rate, N forms, or straw addition. Our long-term experiment in typical greenhouses showed that N application significantly decreased soil pH and increased Ca2+ and Mg2+ leaching loss by 43.1–73.6%, which correlated significantly and positively with nitrate leaching loss. However, optimizing N application and straw incorporation alleviated the leaching loss of Ca2+ and Mg2+ not only by alleviating the accompanying nitrate leaching caused by reduced N input, but also by reducing the conversion of exchangeable Ca2+ and Mg2+ to water-soluble Ca2+ and Mg2+ caused by alleviating soil pH reduction. The laboratory microcosm experiment showed that nitrate application did not reduce soil pH, but significantly increased the leaching loss of Ca2+ and Mg2+. Ammonium sulfate application also significantly increased the leaching loss of Ca2+ and Mg2+, whereas the effects were significantly reversed by nitrification inhibitors. These results further supported the importance of nitrate leaching in promoting the Ca2+ and Mg2+ losses. Together, this study revealed new insights into the dynamics of cation losses mainly regulated by nitrate leaching loss, highlighting that optimizing N management is an effective strategy to alleviate base cation losses and subsequent soil acidification for sustainable agricultural management.

Abstract Background Tracheobronchomegaly (TBM) is a rare disorder mainly characterized by dilatation and malacia of the trachea and major bronchi with diverticularization. This will be a great challenge for airway management, especially in thoracic surgery requiring one-lung ventilation. Using a laryngeal mask airway and a modified double-lumen Foley catheter (DFC) as a “blocker” may achieve one-lung ventilation. This is the first report introducing this method in a patient with TBM. Case presentation We present a 64-year-old man with TBM receiving left lower lobectomy. Preoperative chest computed tomography demonstrated a prominent tracheobronchial dilation and deformation with multiple diverticularization. The most commonly used double-lumen tube or bronchial blocker could not match the distorted airways. After general anesthesia induction, a 4# laryngeal mask was inserted, through which the modified DFC was positioned in the left main bronchus with the guidance of a fiberoptic bronchoscope. The DFC balloon was inflated with 10 ml air and lung isolation was achieved without any significant air leak during one-lung or two-lung ventilation. However, the collapse of the non-dependent lung was delayed and finally achieved by low-pressure artificial pneumothorax. The surgery was successful and the patient was extubated soon after the surgery. Conclusions Using a laryngeal mask airway with a modified double-lumen Foley catheter acted as a bronchial blocker could be an alternative method to achieve lung isolation.

Abstract Learning-based computer-generated hologram (CGH) demonstrates great potential for real-time high-quality holographic displays. However, real-time 4K CGH generation for 3D scenes remains a challenge due to the computational burden. Here, a variant conventional neural network (CNN) is presented for CGH encoding with learned layered initial phases for layered CGH generation. Specifically, the CNN predicts the CGH based on the input complex amplitude on the CGH plane, and the learned initial phases act as a universal phase for any target images at the target depth layer. These phases are generated during the training process of the coding CNN to further optimize the quality. The CNN is trained to learn encoding 3D CGH by randomly selecting the depth layer in the training process, and contains only 938 parameters. The generation time for a 2D 4K CGH is 18 ms, and is increased by 12 ms for each layer in a layered 3D scene. The average Peak Signal to Noise Ratio (PSNR) of each layer is above 30dB in the depth range from 160 to 210 mm. Experiments verify that our method can achieve real-time layered 4K CGH generation.

Abstract Kesterite Cu2ZnSn(S,Se)4 (CZTSSe) is a promising candidate for photodetector (PD) applications thanks to its excellent optoelectronic properties. In this work, a green solution‐ processed spin coating and selenization‐processed thermodynamic or kinetic growth of high‐quality narrow bandgap kesterite CZTSSe thin film is developed. A self‐powered CZTSSe/CdS thin‐film PD is then successfully fabricated. Under optimization of light absorber and heterojunction interface, especially tailoring the defect and carrier kinetics, it can achieve broadband response from 300 to 1300 nm, accompanied with a high responsivity of 1.37 A/W, specific detectivity (D*) up to 4.0 × 1014 Jones under 5 nW/cm2, a linear dynamic range (LDR) of 126 dB, and a maximum Ilight/Idark ratio of 1.3 × 108 within the LDR, and ultrafast response speed (rise/decay time of 16 ns/85 ns), representing the leading‐level performance to date, which is superior to those of commercial and well‐researched photodiodes. Additionally, an imaging system with a 905 nm laser is built for weak light response evaluation, and can respond to 718 pW weak light and infrared imaging at a wavelength as low as 5 nW/cm2. It has also been employed for photoplethysmography detection of pulsating signals at both the finger and wrist, presenting obvious arterial blood volume changes, demonstrating great application potential in broadband and weak light photodetection scenarios.

Abstract Background There is limited longitudinal evidence on the hypertensive effects of long-term exposure to ambient O3. We investigated the association between long-term O3 exposure at workplace and incident hypertension, diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP), and mean arterial pressure (MAP) in general working adults. Methods We conducted a cohort study by recruiting over 30,000 medical examination attendees through multistage stratified cluster sampling. Participants completed a standard questionnaire and comprehensive medical examination. Three-year ambient O3 concentrations at each employed participant’s workplace were estimated using a two-stage machine learning model. Mixed-effects Cox proportional hazards models and linear mixed-effects models were used to examine the effect of O3 concentrations on incident hypertension and blood pressure parameters, respectively. Generalized additive mixed models were used to explore non-linear concentration-response relationships. Results A total of 16,630 hypertension-free working participants at baseline finished the follow-up. The mean (SD) O3 exposure was 45.26 (2.70) ppb. The cumulative incidence of hypertension was 7.11 (95% CI: 6.76, 7.47) per 100 person-years. Long-term O3 exposure was independently, positively and non-linearly associated with incident hypertension (Hazard ratios (95% CI) for Q2, Q3, and Q4 were 1.77 (1.34, 2.36), 2.06 (1.42, 3.00) and 3.43 (2.46, 4.79), respectively, as compared with the first quartile (Q1)), DBP (β (95% CI) was 0.65 (0.01, 1.30) for Q2, as compared to Q1), SBP (β (95% CI) was 2.88 (2.00, 3.77), 2.49 (1.36, 3.61) and 2.61 (1.64, 3.58) for Q2, Q3, and Q4, respectively), PP (β (95% CI) was 2.12 (1.36, 2.87), 2.03 (1.18, 2.87) and 2.14 (1.38, 2.90) for Q2, Q3, and Q4, respectively), and MAP (β (95% CI) was 1.39 (0.76, 2.02), 1.04 (0.24, 1.84) and 1.12 (0.43, 1.82) for Q2, Q3, and Q4, respectively). The associations were robust across sex, age, BMI, and when considering PM2.5 and NO2. Conclusions To our knowledge, this is the first cohort study in the general population that demonstrates the non-linear hypertensive effects of long-term O3 exposure. The findings are particularly relevant for policymakers and researchers involved in ambient pollution and public health, supporting the integration of reduction of ambient O3 into public health interventions.

Bi2O2Se is considered one of the most promising thermoelectric (TE) materials for combining with p-type BiCuSeO in a TE module given its unique chemical and thermal stability. However, the enhancement of its dimensionless figure of merit, zT value, remains a challenge because of its low electrical conductivity. Herein, we introduce KCl into Bi2O2Se, synthesized by solid-state reaction and spark plasma sintering method, to improve its TE properties. The synthesized samples show an outstanding enhancement in electrical conductivity, carrier concentration, and power factor after KCl doping. The Bi2O2Se-based sample with a 0.05% KCl doping content possesses a high zT value of ~0.58 at 773 K, which is over 50% enhancement compared with the pristine Bi2O2Se sample. We also prove that the K element substitutes the Bi site, and Cl replaces the Se site by X-ray diffraction results and density functional theory calculation, supporting that K can improve the electrical conductivity by the position of Fermi level which is above the conduction band minimum. Experimental and theoretical results indicate the success of co-doping with a small amount of KCl and show a huge potential of this novel method for Bi2O2Se TE performance improvement.

Abstract Background Reconstruction of the temporomandibular joint (TMJ) is a significant challenge in maxillofacial surgery. A vascularized medial femoral condyle (MFC) osteocartilaginous flap is a good choice for TMJ reconstruction. In this study, we evaluated the radiographic and histological changes of MFC after TMJ reconstruction. Methods A ramus-condyle unit (RCU) defect was created unilaterally in five adult male Bama miniature pigs. The ipsilateral vascularized MFC osteocartilaginous flap was used to reconstruct the TMJ, and the non-operative sides served as controls. Multislice spiral computed tomography (CT) was performed preoperatively, immediately postoperatively, and at two weeks, three months, and six months postoperatively. Three animals were euthanized at 6 months postoperatively. Their reconstructed condyles, natural condyles and the MFCs on the opposite side were collected and subjected to µCT and histological evaluation. Results In the miniature pigs, the vascularized MFC osteocartilaginous flap was fused to the mandible, thus restoring the structure and function of the RCU. The postoperative radiographic changes and histological results showed that the reconstructed condyle was remodeled toward the natural condyle, forming a similar structure, which was significantly different from the MFC. Conclusions In miniature pigs, the RCU can be successfully reconstructed by vascularized osteocartilaginous MFC flap. The reconstructed condyle had almost the same appearance and histological characteristics as the natural condyle.

In this paper, we focus on non-integrable distributions with a quarter-symmetric non-metric connection (QSNMC) in generalized Riemannian manifold. First, by studying a quarter-symmetric connection on the generalized Riemannian manifold, we obtain the condition that the connection is non-metric. Then, the Gauss, Codazzi and Ricci equations are proved for non-integrable distributions with respect to a quarter-symmetric non-metric connection in generalized Riemannian manifold. Furthermore, we deduce Chen’s inequalities for non-integrable distributions of real space forms with a quarter-symmetric non-metric connection in generalized Riemannian manifold as applications. After that, we give some examples of non-integrable distributions in Riemannian manifold with quarter-symmetric non-metric connection.

The detection of tomatoes is of vital importance for enhancing production efficiency, with image recognition-based tomato detection methods being the primary approach. However, these methods face challenges such as the difficulty in extracting small targets, low detection accuracy, and slow processing speeds. Therefore, this paper proposes an improved RT-DETR-Tomato model for efficient tomato detection under complex environmental conditions. The model mainly consists of a Swin Transformer block, a BiFormer module, path merging, multi-scale convolutional layers, and fully connected layers. In this proposed model, Swin Transformer is chosen as the new backbone network to replace ResNet50 because of its superior ability to capture broader global dependency relationships and contextual information. Meanwhile, a lightweight BiFormer block is adopted in Swin Transformer to reduce computational complexity through content-aware flexible computation allocation. Experimental results show that the average accuracy of the final RT-DETR-Tomato model is greatly improved compared to the original model, and the model training time is greatly reduced, demonstrating better environmental adaptability. In the future, the RT-DETR-Tomato model can be integrated with intelligent patrol and picking robots, enabling precise identification of crops and ensuring the safety of crops and the smooth progress of agricultural production.

Self-desiccation-induced shrinkage may result in cracking at an early age, which is averse to the durability of concrete. Internal curing (IC) agents, such as superabsorbent polymers (SAP), are normally used for moisture regulation and shrinkage reduction. In addition, the make-up of recycled shale lightweight aggregate (RSLA) results in a good absorbing capacity, which makes it a potential candidate for IC. In this paper, the synergistic effect of SAP and RSLA on the relative humidity (RH) variation in early-age concrete under sealed conditions is investigated experimentally in terms of the setting time, relative humidity, and autogenous shrinkage. The results indicate that adding SAP and presoaked RSLA can significantly postpone the initial and final setting times. The initial setting time of RSLA30 and SAP06 is delayed by 127 and 171 min, respectively, compared to the benchmark mixture. In addition, increasing the amounts of SAP and presoaked RSLA can effectively extend the duration of the vapour-saturated stage, reducing the decrease in RH and autogenous shrinkage at 28 days. When the RSLA dosage increases from 0 to 10%, 20%, and 30%, the duration of the vapour-saturated stage is extended by 2, 9.4, and 26 days, respectively. Moreover, due to different water desorption behaviours, more IC water released by RSLA during the initial stage can slow the water release of SAP and lead to a higher RH level at 28 days.

Urban green spaces are an indispensable part of the ecology of cities, serving as the city’s “purifier” and playing a crucial role in promoting sustainable urban development. Therefore, the refined classification of urban green spaces is an important task in urban planning and management. Traditional methods for the refined classification of urban green spaces heavily rely on expert knowledge, often requiring substantial time and cost. Hence, our study presents a multi-label image classification model based on MobileViT. This model integrates the Triplet Attention module, along with the LSTM module, to enhance its label prediction capabilities while maintaining its lightweight characteristic for standalone operation on mobile devices. Trial outcomes in our UGS dataset in this study demonstrate that the approach we used outperforms the baseline by 1.64%, 3.25%, 3.67%, and 2.71% in mAP,F1,precision, and recall, respectively. This indicates that the model can uncover the latent dependencies among labels to enhance the multi-label image classification device’s performance. This study provides a practical solution for the intelligent and detailed classification of urban green spaces, which holds significant importance for the management and planning of urban green spaces.

The global climate change events are expected to augment the vulnerability of persistent organic pollutants within the global brownfield areas to a certain extent, consequently heightening the risk crises faced by these brownfields amidst the backdrop of global environmental changes. However, studies addressing brownfield risks from the perspective of climate change have received limited attention. Nonetheless, the detrimental consequences of brownfield risks are intrinsically linked to strategies for mitigating and adapting to sustainable urban development, emphasizing the critical importance of their far-reaching implications. This relevance extends to concerns about environmental quality, safety, health risks, and the efficacy of chosen regeneration strategies, including potential secondary pollution risks. This comprehensive review systematically surveys pertinent articles published between 1998 and 2023. A selective analysis was conducted on 133 articles chosen for their thematic relevance. The findings reveal that: (1) Under the backdrop of the climate change process, brownfield restoration is necessitated to provide scientific and precise guidance. The integration of brownfield considerations with the dynamics of climate change has progressively evolved into a unified framework, gradually shaping a research paradigm characterized by “comprehensive + multi-scale + quantitative” methodologies; (2) Research themes coalesce into five prominent clusters: “Aggregation of Brownfield Problem Analysis”, “Precision Enhancement of Brownfield Identification through Information Technology”, “Diversification of Brownfield Reutilization Assessment”, “Process-Oriented Approaches to Brownfield Restoration Strategies”, and “Expansion of Ecological Service Functions in Brownfield Contexts”; (3) Application methodologies encompass five key facets: “Temporal and Spatial Distribution Patterns of Pollutants”, “Mechanisms and Correlations of Pollution Effects”, “Evaluation of Pollution Risks”, “Assessment of Brownfield Restoration Strategies”, and “Integration of Brownfield Regeneration with Spatial Planning”. Future brownfield research from the climate change perspective is poised to reflect characteristics such as “High-Precision Prediction, Comprehensive Dimensionality, Full-Cycle Evaluation, Low-Risk Exposure, and Commitment to Sustainable Development”.

BackgroundPoor glycemic control with elevated levels of hemoglobin A1c (HbA1c) is associated with increased risk of cognitive impairment, with potentially varying effects between sexes. However, the causal impact of poor glycemic control on white matter brain aging in men and women is uncertain.MethodsWe used two nonoverlapping data sets from UK Biobank cohort: gene-outcome group (with neuroimaging data, (N = 15,193; males/females: 7,101/8,092)) and gene-exposure group (without neuroimaging data, (N = 279,011; males/females: 122,638/156,373)). HbA1c was considered the exposure and adjusted “brain age gap” (BAG) was calculated on fractional anisotropy (FA) obtained from brain imaging as the outcome, thereby representing the difference between predicted and chronological age. The causal effects of HbA1c on adjusted BAG were studied using the generalized inverse variance weighted (gen-IVW) and other sensitivity analysis methods, including Mendelian randomization (MR)-weighted median, MR-pleiotropy residual sum and outlier, MR-using mixture models, and leave-one-out analysis.ResultsWe found that for every 6.75 mmol/mol increase in HbA1c, there was an increase of 0.49 (95% CI = 0.24, 0.74; p-value = 1.30 × 10−4) years in adjusted BAG. Subgroup analyses by sex and age revealed significant causal effects of HbA1c on adjusted BAG, specifically among men aged 60–73 (p-value = 2.37 × 10−8).ConclusionPoor glycemic control has a significant causal effect on brain aging, and is most pronounced among older men aged 60–73 years, which provides insights between glycemic control and the susceptibility to age-related neurodegenerative diseases.

Background: The association of specific PM2.5 chemical constituents with childhood overweight or obesity (OWOB) remain unclear. Furthermore, the long-term impacts of PM2.5 exposure on the trajectory of children's body mass index (BMI) have not been explored. Methods: We conducted a longitudinal study among 1,450,830 Chinese children aged 6–19 years from Beijing and Zhongshan in China during 2005–2018 to examine the associations of PM2.5 and its chemical constituents with incident OWOB risk. We extracted PM2.5 mass and five main component exposure from Tracking Air Pollution in China (TAP) dataset. Cox proportional hazards models were applied to quantify exposure–response associations. We further performed principal component analysis (PCA) to handle the multi-collinearity and used quantile g-computation (QGC) approach to analyze the impacts of exposure mixtures. Additionally, we selected 125,863 children with at least 8 physical examination measurements and combined group-based trajectory models (GBTM) with multinomial logistic regression models to explore the impacts of exposure to PM2.5 mass and five constituents on BMI and BMI Z-score trajectories during 6–19 years. Results: We observed each interquartile range increment in PM2.5 exposure was significantly associated with a 5.1 % increase in the risk of incident OWOB (95 % confidence Interval [CI]: 1.036–1.066). We also found black carbon, sulfate, organic matter, often linked to fossil combustion, had comparable or larger estimates of the effect (HR = 1.139–1.153) than PM2.5. Furthermore, Exposure to PM2.5 mass, sulfate, nitrate, ammonium, organic matter and black carbon was significantly associated with an increased odds of being in a larger BMI trajectory and being assigned to persistent OWOB trajectory. Conclusions: Our findings provide evidence that the constituents mainly from fossil fuel combustion may have a perceptible influence on increased OWOB risk associated with PM2.5 exposure in China. Moreover, long-term exposure to PM2.5 contributes to an increased odds of being in a lager BMI and a persistent OWOB trajectories.

Objective The objective is to explore whether the flagellin-TLR5 complex signal can enhance the antigen presentation ability of myeloid DCs through the TRIF-ERK1/2 pathway, and the correlation between this pathway and intestinal mucosal inflammation response. Methods Mouse bone marrow-derived DC line DC2.4 was divided into four groups: control group (BC) was DC2.4 cells cultured normally; flagellin single signal stimulation group (DC2.4+CBLB502) was DC2.4 cells stimulated with flagellin derivative CBLB502 during culture; TLR5-flagellin complex signal stimulation group (ov-TLR5-DC2.4+CBLB502) was flagellin derivative CBLB502 stimulated ov-TLR5-DC2.4 cells with TLR5 gene overexpression; TRIF signal interference group (ov-TLR5-DC2.4+CBLB502+Pepinh-TRIFTFA) was ov-TLR5-DC2.4 cells with TLR5 gene overexpression stimulated with flagellin derivative CBLB502 and intervened with TRIF-specific inhibitor Pepinh-TRIFTFA. WB was used to detect the expression of TRIF and p-ERK1/2 proteins in each group of cells; CCK8 was used to detect cell proliferation in each group; flow cytometry was used to detect the expression of surface molecules MHCI, MHCII, CD80, 86 in each group of cells; ELISA was used to detect the levels of IL-12 and IL-4 cytokines in each group. Results Compared with the BC group, DC2.4+CBLB502 group, and ov-TLR5-DC2.4+CBLB502+Pepinh-TRIFTFA group, the expression of TRIF protein and p-ERK1/2 protein in ov-TLR5-DC2.4+CBLB502 group was significantly upregulated (TRIF: p = 0.02, = 0.007, = 0.048) (ERK1: p

Summary: Background: HIV self-testing (HIVST) offers potential solutions to challenges associated with site-based HIV testing (SBHT). However, the effectiveness of HIVST as an HIV prevention strategy for men who have sex with men (MSM) discontinuing pre-exposure prophylaxis (PrEP) after the completion of PrEP demonstration project has rarely been assessed. Methods: The China Real-world Study of Oral PrEP (CROPrEP) project was conducted in four cities in China. Participants were directed to community resources to continue their PrEP medication after the discontinuation of project-provided PrEP at the last CROPrEP visit. We conducted a multicentre open-label randomized controlled trial among MSM who had discontinued PrEP induced by the completion of CROPrEP. Eligible participants were randomly assigned to either the intervention group or the control group (1:1). Participants received regular health education and behavioural interventions throughout the trial. The intervention group was given a link to order free HIVST kits online, while the control group received information about free SBHT. Both groups completed internet-based follow-up surveys at three and six months. The primary outcome was the proportion of participants who underwent HIV testing during the six-month follow-up period. This trial was registered at chictr.org.cn (ChiCTR2000038416). Findings: Between November 2020 and January 2021, we recruited a total of 620 participants (300 in the intervention group and 320 in the control group). The follow-up completion rates were 99·0% and 95·0% in the intervention and control groups, respectively. At baseline, the median age of participants was 32 (interquartile range: 26–37), and 77·7% underwent HIV testing in the past three months. The proportion of participants who underwent HIV testing in the past three months was higher in the intervention group than in the control group at both the three-month (adjusted risk difference [RD]: 36·7, 95% confidence interval [CI]: 35·1–38·5, p

BackgroundFew studies have investigated the association between air pollution and arterial stiffness in Chinese population, and the findings are inconsistent. The problem of multicollinearity exists when modeling multiple air pollutants simultaneously. ObjectiveTo investigate potential association between air quality index (AQI) and population brachial-ankle pulse wave velocity (baPWV) in Beijing. MethodsThis study retrieved medical examination data of 2971 participants from the Beijing Health Management Cohort, who were under 60 years old and not yet retired, from January 1, 2015 to December 31, 2019. The most recent medical examination data available were utilized for this analysis. AQI data from 35 air pollution monitoring sites in Beijing and meteorological data (including atmospheric pressure, air temperature, wind speed, and relative humidity) from 16 meteorological monitoring stations from January 1, 2014 to December 31, 2019 were collected. An average AQI exposure level for 365 d before the date of physical examination for each participant was computed using inverse distance weighting. Multiple linear regression analysis was employed to investigate the relationship between AQI and baPWV in Beijing, after adjusting for confounding variables including age, gender, body mass index, mean arterial pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting blood glucose, atmospheric pressure, temperature, wind speed, relative humidity, medication history of diabetes, medication history of hypertension, cardiovascular disease, education, smoking status, drinking status, and physical activity intensity. Subgroup analysis was performed by age, sex, presence of diabetes, and presence of hypertension. ResultsAQI demonstrated an overall decreasing trend during the study period and was lower in the northern regions and higher in the southern regions of Beijing. After adjusting the confounding variables, each 10 unit increase in AQI was associated with 6.18 (95%CI: 1.25, 11.10) cm·s−1 increase in baPWV in all participants, 8.05 (95%CI: 2.32, 13.79) cm·s−1 increase in the participants 0.05). ConclusionAn increase in long-term AQI levels is associated with an elevation in the degree of arterial stiffness. Individuals under 50 years old, females, without hypertension or diabetes are susceptible populations to arterial stiffness when being exposed to air pollution. Improving air quality may contribute to prevent arterial stiffness.

Abstract Orthodontically induced tooth root resorption (OIRR) is a serious complication during orthodontic treatment. Stimulating cementum repair is the fundamental approach for the treatment of OIRR. Parathyroid hormone (PTH) might be a potential therapeutic agent for OIRR, but its effects still lack direct evidence, and the underlying mechanisms remain unclear. This study aims to explore the potential involvement of long noncoding RNAs (lncRNAs) in mediating the anabolic effects of intermittent PTH and contributing to cementum repair, as identifying lncRNA-disease associations can provide valuable insights for disease diagnosis and treatment. Here, we showed that intermittent PTH regulates cell proliferation and mineralization in immortalized murine cementoblast OCCM-30 via the regulation of the Wnt pathway. In vivo, daily administration of PTH is sufficient to accelerate root regeneration by locally inhibiting Wnt/β-catenin signaling. Through RNA microarray analysis, lncRNA LITTIP (LGR6 intergenic transcript under intermittent PTH) is identified as a key regulator of cementogenesis under intermittent PTH. Chromatin isolation by RNA purification (ChIRP) and RNA immunoprecipitation (RIP) assays revealed that LITTIP binds to mRNA of leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and heterogeneous nuclear ribonucleoprotein K (HnRNPK) protein. Further co-transfection experiments confirmed that LITTIP plays a structural role in the formation of the LITTIP/Lgr6/HnRNPK complex. Moreover, LITTIP is able to promote the expression of LGR6 via the RNA-binding protein HnRNPK. Collectively, our results indicate that the intermittent PTH administration accelerates root regeneration via inhibiting Wnt pathway. The lncRNA LITTIP is identified to negatively regulate cementogenesis, which activates Wnt/β-catenin signaling via high expression of LGR6 promoted by HnRNPK.

Abstract Studies of vacancy-mediated anomalous transport properties have flourished in diverse fields since these properties endow solid materials with fascinating photoelectric, ferroelectric, and spin-electric behaviors. Although phononic and electronic transport underpin the physical origin of thermoelectrics, vacancy has only played a stereotyped role as a scattering center. Here we reveal the multifunctionality of vacancy in tailoring the transport properties of an emerging thermoelectric material, defective n-type ZrNiBi. The phonon kinetic process is mediated in both propagating velocity and relaxation time: vacancy-induced local soft bonds lower the phonon velocity while acoustic-optical phonon coupling, anisotropic vibrations, and point-defect scattering induced by vacancy shorten the relaxation time. Consequently, defective ZrNiBi exhibits the lowest lattice thermal conductivity among the half-Heusler family. In addition, a vacancy-induced flat band features prominently in its electronic band structure, which is not only desirable for electron-sufficient thermoelectric materials but also interesting for driving other novel physical phenomena. Finally, better thermoelectric performance is established in a ZrNiBi-based compound. Our findings not only demonstrate a promising thermoelectric material but also promote the fascinating vacancy-mediated anomalous transport properties for multidisciplinary explorations.

[Introduction] Large-scale connection of wind power to the power grid poses great challenges to the stability (especially frequency stability) of grid operation.In order to solve the problem of inadequate frequency regulation capability caused by large-scale connection of wind power to the power grid and improve the frequency adaptability of wind power grid connection, wind turbines need to have frequency regulation function and response timeliness. [Method] This paper adopted a frequency regulation system scheme based on rotor kinetic energy and pitch angle reserve, which could provide active support for the power grid quickly and accurately during the power grid frequency change. Firstly, the main control algorithm was designed based on the theoretical analysis of inertia response and primary frequency regulation algorithm logic. Then, the functional verification was carried out on the co-simulation platform. Finally, the actual test was carried out in a project.[Result] The simulation and test results showed that the frequency regulation system scheme based on rotor kinetic energy and pitch angle reserve could cope with a variety of grid frequency changes and quickly provided active support. [Conclusion] The frequency regulation system scheme of wind turbines can perform a fast inertia response (with the response time less than 500 ms) and primary frequency regulation response (with the response time less than 5 s) under various frequency change conditions and provide active support for the power grid, which can help recover the grid frequency and effectively improve the frequency adaptability of wind turbines.

Highlights A hierarchical interconnected NiMoN (HW-NiMoN-2h) was successfully prepared based on a rational combination of hydrothermal and water bath processes. HW-NiMoN-2h exhibited high hydrogen evolution reaction (HER) activity due to its large specific surface area and good stability due to its enhanced mechanical strength. In 1 M KOH seawater, HW-NiMoN-2h delivered current density of 1 A cm−2 for HER at an overpotential of 130 mV and showed excellent stability over 70 h at 1 A cm−2.

Abstract Small nucleolar RNAs (snoRNAs) are a class of non-coding RNAs widely distributed in eukaryotic nucleoli. In recent years, studies have revealed that snoRNAs can also participate in the occurrence and development of malignant tumors through different pathways. Cervical cancer is one of the most common malignant tumors of the female reproductive system, and the high-risk HPV virus infection is its main pathogenic mechanism. However, the outcomes in different patients with malignant tumors vary, indicating that other factors might affect the pathogenic process of cervical cancer. In this study, we screened the poor prognosis indicator SNORD6 from the TCGA database to find the snoRNA that affects the disease outcome during the pathogenesis of cervical cancer. We discovered that SNORD6 expression in cervical cancer tissues was higher than that in normal cervical tissues. Cell phenotype experiments revealed that the knockdown of SNORD6 retarded cell proliferation and plate clone formation. Furthermore, G1-S phase cell cycle arrest was induced, DNA synthesis was decreased, cell migration and invasion were reduced, while the level of apoptosis increased, whereas the opposite results were obtained after SNORD6 overexpression. Moreover, after intratumoral injection of ASO-SNORD6, the tumor growth rate slowed down, and the tumor volume decreased compared with the control group. In the mechanism study, we found that SNORD6 concurrently acted as a binding “hub” to promote the formation of the tumor suppressor protein p53 degradation complex E6-E6AP-p53. This reaction enhanced the ubiquitination and degradation of p53, thus influenced the regulation of p53 activities in the cell cycle and apoptosis. This study preliminarily clarified the biological role and specific mechanism of SNORD6 in the occurrence of cervical cancer, broadening the basic theoretical research of ovarian cancer and may provide a new perspective on the diagnosis and treatment of cervical cancer.

Abstract Adenosine-to-inosine (A-to-I) editing, a key RNA modification widely found in eukaryotes, is catalyzed by adenosine deaminases acting on RNA (ADARs). Such RNA editing destabilizes endogenous dsRNAs, which are subsequently recognized by the sensors of innate immune and other proteins as autologous dsRNAs. This prevents the activation of innate immunity and type I interferon-mediated responses, thereby reducing the downstream cell death induced by the activation of the innate immune sensing system. ADARs-mediated editing can also occur in mRNAs and non-coding RNAs (ncRNAs) in different species. In mRNAs, A-to-I editing may lead to missense mutations and the selective splicing of coding regions. Meanwhile, in ncRNAs, A-to-I editing may affect targeting and disrupt ncRNAs maturation, leading to anomalous cell proliferation, invasion, and responses to immunotherapy. This review highlights the biological functions of A-to-I editing, its role in regulating innate immunity and cell death, and its potential molecular significance in tumorigenesis and cancer targeted therapy and immunotherapy.