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Abstract Background The goal of the research was to examine the value of peripheral blood indicators in forecasting survival and recurrence among people suffering central‐type non‐small cell lung cancer (NSCLC) undergoing sleeve lobectomy (SL). Methods Clinical information was gathered from 146 individuals suffering from NSCLC who had SL at our facility between January 2014 and May 2023. Peripheral blood neutrophil lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet lymphocyte ratio (PLR) levels were determined by receiver operating characteristic (ROC) curve to establish the threshold points. Kaplan–Meier survival analysis was employed to evaluate the prognostic value of different groupings, and both univariate and multivariate Cox proportional hazards model (referred to as COX) were performed. Results The disease‐free survival (DFS) and overall survival (OS) cutoff values were carried out via ROC analysis. Kaplan–Meier survival analysis revealed notable differences in OS for NLR (≥2.196 vs.

Abstract Background Lung cancer has always a cancer that threatens human health. Quality of life also has been an important research topic. psychological state in patients can influence their quality of life, and perceived social support and coping styles are relevant facilitators of Quality of life, but this specific relationship has not been adequately studied. The purpose of this study is focus on discussing the correlation of these four and understanding their potential mediating pathways. Materials and methods This is a cross-sectional study. A total of 300 Lung Cancer patients from a cancer hospital in Suzhou were surveyed. The Data was collected using the scales. The collected data was analyzed using SPSS and AMOS software. Results The study revealed a significant serial mediation model between perceived social support and coping style: Psychological state regulates patients’ coping styles by influencing their perceived social support which ultimately has comprehensive impacts on their quality of life. Conclusion Based on the empirical results discussed, this study proposes the following suggestion: Provide good online support to form a related social media intervention matrix. meanwhile, expand the patients’ social network offline, provide channels for patients to express their troubles outwardly, and regularly assess the patients’ psychological status to improve their level of psychosocial adaptation. This will in turn enhance their negative coping strategies towards the disease and strengthen their ability to buffer against it, ultimately promoting a better quality of life for the patients.

Abstract Mutations in fibrillin 1 (FBN1) is the main cause of Marfan syndrome (MFS) with thoracic aortic aneurysm (TAA) as the main complication. Activation of the complement system plays a key role in the formation of thoracic and abdominal aortic aneurysms. However, the role of the complement system in MFS-associated aortic aneurysms remains unclear. In this study, we observed increased levels of complement C3a and C5a in the plasma of MFS patients and mouse, and the increased deposition of the activated complement system product C3b/iC3b was also observed in the elastic fiber rupture zone of 3-month-old MFS mice. The expression of C3a receptor (C3aR) was increased in MFS aortas, and recombinant C3a promoted the expression of cytokines in macrophages. The administration of a C3aR antagonist (C3aRA) attenuated the development of thoracic aortic aneurysms in MFS mice. The increased inflammation response and matrix metalloproteinases activities were also attenuated by C3aRA treatment in MFS mice. Therefore, these findings indicate that the complement C3a/C3aR inhibition alleviates the formation of aortic aneurysm in Marfan syndrome mice.

Abstract PARP inhibitor (PARPi) therapy has transformed outcomes for patients with homologous recombination DNA repair (HRR) deficient ovarian cancers, for example those with BRCA1 or BRCA2 gene defects. Unfortunately, PARPi resistance is common. Multiple resistance mechanisms have been described, including secondary mutations that restore the HR gene reading frame. BRCA1 splice isoforms △11 and △11q can contribute to PARPi resistance by splicing out the mutation-containing exon, producing truncated, partially functional proteins. However, the clinical impacts and underlying drivers of BRCA1 exon skipping are not fully understood. We analyzed nine ovarian and breast cancer patient derived xenografts (PDX) with BRCA1 exon 11 frameshift mutations for exon skipping and therapy response, including a matched PDX pair derived from a patient pre- and post-chemotherapy/PARPi. BRCA1 exon 11 skipping was elevated in PARPi resistant PDX tumors. Two independent PDX models acquired secondary BRCA1 splice site mutations (SSMs) that drive exon skipping, confirmed using qRT-PCR, RNA sequencing, immunoblotting and minigene modelling. CRISPR/Cas9-mediated disruption of splicing functionally validated exon skipping as a mechanism of PARPi resistance. SSMs were also enriched in post-PARPi ovarian cancer patient cohorts from the ARIEL2 and ARIEL4 clinical trials. Few PARPi resistance mechanisms have been confirmed in the clinical setting. While secondary/reversion mutations typically restore a gene’s reading frame, we have identified secondary mutations in patient cohorts that hijack splice sites to enhance mutation-containing exon skipping, resulting in the overexpression of BRCA1 hypomorphs, which in turn promote PARPi resistance. Thus, BRCA1 SSMs can and should be clinically monitored, along with frame-restoring secondary mutations.

Abstract As a crucial nonlinear phenomenon, stimulated Raman scattering (SRS) plays multifaceted roles involved in forward and inverse problems. In fibre-optic systems, these roles range from detrimental interference that impairs optical performance to beneficial effects that enables various devices such as Raman amplifier. To obtain solutions of SRS, various numerical methods customized for different scenarios have been proposed. However, these methods are time-consuming, low-efficiency, and experience-orientated, particularly in combined scenarios consisting of both forward and inverse problems. Inspired by physics-informed neural networks, we propose SRS-Net, which combines the efficient automatic differentiation and powerful representation ability of neural networks with the regularization of SRS physical laws, to obtain universal solutions for SRS of forward, inverse, and combined problems. We showcase the intuitive solving procedure and high-speed performance of SRS-Net through extensive simulations covering different scenarios. Additionally, we validate its capabilities in experiments involving the high-fidelity modelling of a wavelength division multiplexing system spanning the C + L-band with approximately 10 THz. The versatility of the SRS-Net framework extends beyond SRS, indicating its potential as a promising universal solution in other engineering problems with nonlinear dynamics governed by partial differential equations.

Abstract Although nanocatalytic medicine has demonstrated its advantages in tumor therapy, the outcomes heavily relie on substrate concentration and the metabolic pathways are still indistinct. We discover that violet phosphorus quantum dots (VPQDs) can catalyze the production of reactive oxygen species (ROS) without requiring external stimuli and the catalytic substrates are confirmed to be oxygen (O2) and hydrogen peroxide (H2O2) through the computational simulation and experiments. Considering the short of O2 and H2O2 at the tumor site, we utilize calcium peroxide (CaO2) to supply catalytic substrates for VPQDs and construct nanoparticles together with them, named VPCaNPs. VPCaNPs can induce oxidative stress in tumor cells, particularly characterized by a significant increase in hydroxyl radicals and superoxide radicals, which cause substantial damage to the structure and function of cells, ultimately leading to cell apoptosis. Intriguingly, O2 provided by CaO2 can degrade VPQDs slowly, and the degradation product, phosphate, as well as CaO2-generated calcium ions, can promote tumor calcification. Antitumor immune activation and less metastasis are also observed in VPCaNPs administrated animals. In conclusion, our study unveils the anti-tumor activity of VPQDs as catalysts for generating cytotoxic ROS and the degradation products can promote tumor calcification, providing a promising strategy for treating tumors.

Abstract Documenting tangible cultural heritage using 3D modeling techniques is gradually becoming an indispensable component of archaeological practice. The 3D modeling techniques based on photogrammetry and LiDAR scanning enable high-accuracy and high-realistic reconstruction of archaeological sites, and have been proven a powerful tool for documenting archaeological excavations. However, dynamically documenting an ongoing excavation using these techniques is still considered tedious, time-consuming, expensive, and dependent on expertise. Moreover, the application of 3D modeling techniques in archaeological excavations still faces some technical challenges, such as modeling with multi-source and multi-scale data, fusing local models at different times into a whole, achieving fast modeling while GPU workstations are not available in the field, and evaluating the quality of 3D models. As a result, there are still very few archaeological teams deeply engaged in dynamic documentation with 3D modeling techniques, and traditional drawing sketches and taking photographs still dominate. In these senses, documenting the archaeological excavation at the Yunxian Man site (located in Hubei, China) is an invaluable opportunity for exploration and practice. Archaeologists determined to conduct dynamically documenting at the beginning of the 6th excavation project for the site, and established a rotation system to reconcile physical excavation with digital preservation. Through repeated practice and communication, we proposed a workflow and pursued several new methods to enhance the feasibility of dynamically documenting, and obtained 4D models of the ongoing archaeological excavations. In 2022, the Yunxian Man site unearthed the most intact fossil of hominin cranium from about one million years ago in the Eurasian continent, preserving important and scarce anatomical features of early humans in Asia. As the original taphonomic context of the fossil corroded away during physical excavations, the digital documentation consisting of 4D models serves as permanent original data source in subsequent archaeological research. Moreover, we obtained cross-scale 3D models from geographical environment to archaeological site, excavation area, and cultural remains, and all of these 3D models are in an actual, unified coordinate framework. Thus, we can contribute to multidisciplinary cross-collaborative research through data sharing. Considering that digital documentations serve a great value in archaeological research, this paper focuses on sharing the workflow and methods to facilitate digital preservation for more archaeological projects.

Objective: To investigate the effectiveness of the original oblique conformal anastomosis presented in this research in reducing the incidence of cervical anastomotic leak after performing totally minimally invasive esophagectomy (TMIE). Methods: The esophagus and stomach of 27 fresh pigs, termed the esophagogastric model, were used to simulate human esophagogastric organs for this study's in vitro experimental objectives. Nine esophagogastric models of similar weight were divided into three groups. Esophagogastrostomy with circular-stapled end-to-side anastomosis was performed. A tension gauge was used to pull the anastomosis, and the tension at which anastomotic leakage occurred was recorded. Furthermore, a retrospective assessment of 539 patients who underwent TMIE was conducted to analyze the influencing factors of cervical anastomotic leakage. Results: Experiments on the esophagogastric models showed a higher fracture strength of oblique conformal anastomosis than that of conventional anastomosis (F2,18 = 40.86, P

Abstract Background Chronic pain was associated with a higher risk of mental disorders (e.g., depression and anxiety). However, the role of 24-h movement behaviors in the association remains unclear. Methods A total of 72,800 participants with accelerometer data and free of mental disorders from the UK Biobank were analyzed. The compositional mediation model and isotemporal substitution model were used to explore the associations between chronic pain, 24-h movement behaviors, and the incidence of overall mental disorders, depression, and anxiety. Results With a median follow-up of 13.36 years, participants with chronic pain had a higher rate of incident overall mental disorders (hazard ratio (HR): 1.281, 95% confidence interval (CI): 1.219 to 1.344), anxiety (HR: 1.391, 95% CI: 1.280 to 1.536), and depression (HR: 1.703, 95% CI: 1.551 to 1.871). Increased sedentary behavior (SB) and reduced moderate-to-vigorous physical activity (MVPA) caused by chronic pain both increased the risk of mental disorders. Twenty-four-hour movement behaviors explained the relationship between chronic pain and overall mental disorders, depression, and anxiety by 10.77%, 5.70%, and 6.86%, respectively. Interaction effects were found between MVPA and chronic pain when predicting the incidence of depression and between MVPA, sleep (SLP), and chronic pain when predicting the incidence of mental disorders. People with chronic pain would recommend at least 0.5 h per day of MVPA and 7 h per day of SLP and restricting SB below 11.5 h per day. Conclusions Twenty-four-hour movement behaviors played a significant mediating role in the association between chronic pain and mental disorders. Individuals with chronic pain should engage in more MVPA, less sedentary behavior, and have 7-h sleep per day.

Abstract Under subarachnoid hemorrhage (SAH) conditions, astrocytes undergo a marked intensification of glycolytic activity, resulting in the generation of substantial amounts of lactate to maintain the energy demand for neurons and other brain cells. Lactate has garnered increasing attention in recent years because of its emerging role in critical biological processes such as inflammation regulation and neuroprotection, particularly through its histone lactylation. Bromodomain-containing protein 4 (BRD4) plays a crucial role in maintaining neural development and promoting memory formation in the central nervous system. Nonetheless, the function and regulatory mechanism of BRD4 and histone lactylation in astrocytes following SAH remain elusive. Our findings indicate that BRD4, a crucial epigenetic regulator, plays a definitive role in histone lactylation. Both in vitro and in vivo, these results demonstrated that targeted silencing of BRD4 in astrocytes can significantly reduce H4K8la lactylation, thereby aggravating the A1 polarization of astrocytes and ultimately affecting the recovery of neural function and prognosis in mice after SAH. In summary, BRD4 plays a pivotal role in modulating astrocyte polarization following SAH via histone lactylation. Targeting this mechanism might offer an efficient therapeutic strategy for SAH.

Abstract Artificial-intelligence-generated content has driven explosive data traffic growth in data-center interconnects. Traditional direct detection solutions struggle with limited spectral efficiency and distance, prompting the shift to coherent optics for cost-sensitive short-reach links. One specific challenge is integrating low-cost lasers while overcoming severe phase noise on high-order modulation formats. Here, we propose a residual carrier modulation scheme for precise and efficient carrier frequency and phase recovery. The residual optical carrier can continuously track phase fluctuations without redundancy compared with discrete time-domain pilots, and address the digital-to-analog convertor resolution reduction issue of frequency-domain digital pilots. In proof-of-concept experiments, we transmit a net 1-Tb/s probabilistic-shaped 256-ary quadrature amplitude modulated (PS-256-QAM) signal using a 3 MHz distributed feedback (DFB) laser. Our scheme improves bitrate by 41% compared to conventional time-domain pilots, achieving a record laser linewidth sum and symbol duration product of 6.89 × 10−5. This approach supports MHz linewidth DFB lasers in low-cost coherent optical communications.

Highlights The development history and working mechanism of dual-ion batteries are reviewed, with an emphasis on the latest advancement in anode materials. A comprehensive and detailed summary of the synthesis strategies, structural optimization, performance characterization, and reaction principles of four types of anode materials for dual-ion batteries is presented. The current challenges of anode materials are highlighted, and the optimization strategies of advanced anode materials and battery systems are discussed, providing future research directions for the design of commercial dual-ion batteries.

Abstract Background Depressive symptoms often occur in patients with Alzheimer's disease (AD) and exacerbate the pathogenesis of AD. However, the neural circuit mechanisms underlying the AD-associated depression remain unclear. The serotonergic system plays crucial roles in both AD and depression. Methods We used a combination of in vivo trans-synaptic circuit-dissecting anatomical approaches, chemogenetic manipulations, optogenetic manipulations, pharmacological methods, behavioral testing, and electrophysiological recording to investigate dorsal raphe nucleus serotonergic circuit in AD-associated depression in AD mouse model. Results We found that the activity of dorsal raphe nucleus serotonin neurons (DRN5-HT) and their projections to the dorsal hippocampal CA1 (dCA1) terminals (DRN5-HT-dCA1CaMKII) both decreased in brains of early 5×FAD mice. Chemogenetic or optogenetic activation of the DRN5-HT-dCA1CaMKII neural circuit attenuated the depressive symptoms and cognitive impairments in 5×FAD mice through serotonin receptor 1B (5-HT1BR) and 4 (5-HT4R). Pharmacological activation of 5-HT1BR or 5-HT4R attenuated the depressive symptoms and cognitive impairments in 5×FAD mice by regulating the DRN5-HT-dCA1CaMKII neural circuit to improve synaptic plasticity. Conclusions These findings provide a new mechanistic connection between depression and AD and provide potential pharmaceutical prevention targets for AD.

Objective To analyze the predictive value of cardiovascular magnetic resonance (CMR) myocardial perfusion imaging combined with CT fractional flow reserve(CT-FFR) parameters in predicting cardiovascular adverse events in obstructive coronary heart disease. Methods A prospective study was conducted in 180 patients with obstructive coronary heart disease (coronary artery stenosis ≥ 50%) who were treated in the Second Affiliated Hospital of Hebei North University from June 2018 to June 2022. All patients underwent CT angiography and CMR myocardial perfusion imaging, and the occurrence of cardiovascular adverse events within 1 year was collected by on-site follow-up or telephone follow-up. Univariate and multivariate logistic regression models were used to analyze the influencing factors of cardiovascular adverse events; ROC curves were used to assess the predictive efficacy of different prediction models for the occurrence of cardiovascular adverse events. Results A total of 45 patients developed cardiovascular adverse events (observation group), and the remaining 135 patients were controls. Compared with the control group, the age, male ratio, smoking patient ratio, total cholesterol level, diabetes mellitus ratio, hyperlipidemia ratio, first-pass perfusion time and myocardial delayed enhancement signal value of the observation group increased, while the CT-FFR and maximum slope(Slopemax) index decreased, and the differences were statistically significant (P

Abstract Rabies is a lethal disease caused by the rabies virus (RABV), which causes acute neurological infections in mammals, including human beings. We previously reported that an mRNA vaccine (LVRNA001) encoding the rabies virus’s glycoprotein induced strong protective immune responses to rabies in mice and dogs. Here, we further evaluate the safety of LVRNA001. First, we performed a confirmative efficacy study in dogs, which showed that LVRNA001 fully protected the animals from the virus, both pre- and post-infection. Moreover, using pre- and post-exposure prophylaxis murine models, we showed that LVRNA001, built from the CTN-1 strain, was able to protect against various representative RABV strains from the China I–VII clades. To evaluate the safety of the vaccine, chronic and reproductive toxicity studies were performed with cynomolgus macaques and rats, respectively. In a repeated-dose chronic toxicity study, vaccinated monkeys displayed no significant alterations in body weight, temperature, or hematological and biochemical markers. Lymphocyte subset measurement and histopathological examination showed that no toxicity was associated with the vaccine. The immunogenicity study in cynomolgus macaques demonstrated that LVRNA001 promoted the generation of neutralizing antibodies and Th1-biased immune response. Evaluation of reproductive toxicity in rats revealed that administration of LVRNA001 had no significant effects on fertility, maternal performance, reproductive processes, and postnatal outcomes. In conclusion, LVRNA001 can provide efficient protection against rabies virus infection in dogs and mice, and toxicity studies showed no significant vaccine-related adverse effects, suggesting that LVRNA001 is a promising and safe vaccine candidate for rabies prophylaxis and therapy.

Abstract The study of brain differences across Eastern and Western populations provides vital insights for understanding potential cultural and genetic influences on cognition and mental health. Diffusion MRI (dMRI) tractography is an important tool in assessing white matter (WM) connectivity and brain tissue microstructure across different populations. However, a comprehensive investigation into WM fiber tracts between Eastern and Western populations is challenged due to the lack of a cross-population WM atlas and the large site-specific variability of dMRI data. This study presents a dMRI tractography atlas, namely the East-West WM Atlas, for concurrent WM mapping between Eastern and Western populations and creates a large, harmonized dMRI dataset (n=306) based on the Human Connectome Project and the Chinese Human Connectome Project. The curated WM atlas, as well as subject-specific data including the harmonized dMRI data, the whole brain tractography data, and parcellated WM fiber tracts and their diffusion measures, are publicly released. This resource is a valuable addition to facilitating the exploration of brain commonalities and differences across diverse cultural backgrounds.

Abstract Objective By meticulously tracking the evolving growth, development, and nutritional status of primary and secondary school students in Qiongzhong County from 2014 to 2021 post-implementation of the “Nutrition Improvement Program for Rural Compulsory Education Students”(NIPRCES, This project provides a supplementary food allowance of at least ￥4 per person per day for primary and secondary school students. The project area undergoes annual routine monitoring.), this study aims to offer a scientific basis for enhancing and promoting the project. Through thorough monitoring of students’ nutritional status changes influenced by this program, we strive to establish a comprehensive and evidence-based framework for its future advancement. Methods From 2014 to 2021, this study employed a multi-stage sampling method utilizing cluster sampling to select six primary and six secondary schools in Qiongzhong County, Hainan Province. Data on the growth and development of respondents were collected. This cohort was a dynamic cohort with a total of 18,762 final data recovered. The prevalence of malnutrition was evaluated using the Cochran Armitage Trend Test (CATT) to assess year-to-year changes. Furthermore, height/weight and the prevalence of malnutrition between groups were compared using the t-test, χ2 test, and Bonferroni’s corrected analysis. Results The average height of both boys and girls has increased. In 2021, boys and girls of all ages showed an average height increase of 2.31 cm and 1.98 cm, respectively, compared to 2014. Nevertheless, the growth and development levels, and rate of improvement of these students remain comparatively lower than their rural counterparts across China, who are of the same age. From 2014 to 2021, the prevalence of undernutrition (mainly wasting) showed a significant downward trend (P

This paper aims to study the impact of CEOs' cultural background on corporate innovation. The paper constructs a measure of CEOs' cultural individualism based on their birthplaces and investigates its relationship with firms' patents and citations. The study aims to shed light on the interaction of culture and corporate decisions and focuses on the role of top managers. The paper also investigates the mechanism of how top management can affect corporate innovation output. The paper constructs the measure of individualism using the westward expansion in US history. To do so, the paper uses the US county-level duration of exposure of the frontier territory in the 19th century and links the counties to CEOs' birthplaces. The paper argues the cultural characteristics of birthplaces can affect a person's later management styles and decisions, hence affecting corporate innovation policies. Using regression and difference-in-differences estimations, the paper explores the relation and causality between cultural individualism and innovation output. The paper finds that CEO cultural individualism is positively related with the number of patents produced by the firm and the citations received by the firm. Difference-in-differences tests using CEO turnovers support that the relation is causal. The paper also investigates the economic mechanism of how individualistic CEOs achieve such results. It finds that individualistic CEOs tend to hire more talented employees and improve the workplace environment to attract top inventors. This paper provides firm-level evidence of culture and innovation. Prior studies in this area focus on cross-country evidence and suffer the limitation of confounding factors. Using a county-level measure of individualism and a sample of firms in USA, the paper alleviates the concern and provides evidence with better granularity. This paper also provides a novel mechanism for attracting top inventors, while existing literature tend to focus on risk-taking activities.

Abstract Background Computed tomography (CT) is the usual modality for diagnosing stroke, but conventional CT angiography reconstructions have limitations. Methods A phantom with tubes of known diameters and wall thickness was scanned for wall detectability, wall thickness, and contrast-to-noise ratio (CNR) on conventional and spectral black-blood (SBB) images. The clinical study included 34 stroke patients. Diagnostic certainty and conspicuity of normal/abnormal intracranial vessels using SBB were compared to conventional. Sensitivity/specificity/accuracy of SBB and conventional were compared for plaque detectability. CNR of the wall/lumen and quantitative comparison of remodeling index, plaque burden, and eccentricity were obtained for SBB imaging and high-resolution magnetic resonance imaging (hrMRI). Results The phantom study showed improved detectability of tube walls using SBB (108/108, 100% versus conventional 81/108, 75%, p

Abstract Sirenians of the superorder Afrotheria were the first mammals to transition from land to water and are the only herbivorous marine mammals. Here, we generated a chromosome-level dugong (Dugong dugon) genome. A comparison of our assembly with other afrotherian genomes reveals possible molecular adaptations to aquatic life by sirenians, including a shift in daily activity patterns (circadian clock) and tolerance to a high-iodine plant diet mediated through changes in the iodide transporter NIS (SLC5A5) and its co-transporters. Functional in vitro assays confirm that sirenian amino acid substitutions alter the properties of the circadian clock protein PER2 and NIS. Sirenians show evidence of convergent regression of integumentary system (skin and its appendages) genes with cetaceans. Our analysis also uncovers gene losses that may be maladaptive in a modern environment, including a candidate gene (KCNK18) for sirenian cold stress syndrome likely lost during their evolutionary shift in daily activity patterns. Genomes from nine Australian locations and the functionally extinct Okinawan population confirm and date a genetic break ~10.7 thousand years ago on the Australian east coast and provide evidence of an associated ecotype, and highlight the need for whole-genome resequencing data from dugong populations worldwide for conservation and genetic management.

Abstract Microengineering the dielectric layers with three-dimensional microstructures has proven effective in enhancing the sensitivity of flexible pressure sensors. However, the widely employed geometrical designs of solid microstructures exhibit limited sensitivity over a wide range of pressures due to their inherent but undesired structural compressibility. Here, a Marangoni-driven deterministic formation approach is proposed for fabricating hollow microstructures, allowing for greater deformation while retarding structural stiffening during compression. Fluid convective deposition enables solute particles to reassemble in template microstructures, controlling the interior cavity with a void ratio exceeding 90%. The hollow micro-pyramid sensor exhibits a 10-fold sensitivity improvement across wider pressure ranges over the pressure sensor utilizing solid micro-pyramids, and an ultra-low detect limit of 0.21 Pa. With the advantages of facilitation, scalability, and large-area compatibility, such an approach for hollow microstructures can be expanded to other sensor types for superior performance and has considerable potential in robotic tactile and epidermal devices.

To evaluate the risk of acquiring syphilis from a donated kidney, we evaluated kidney transplantation pairs from West China Hospital, Sichuan, China, during 2007–2022. Donor-derived syphilis was rare. Risk may be higher if donors have active syphilis and may be reduced if recipients receive ceftriaxone.

Abstract Introduction Early prediction of abrocitinib efficacy in atopic dermatitis (AD) could help identify candidates for an early dose increase. A predictive model determined week 12 efficacy based on week 4 responses in patients receiving abrocitinib 100 mg/day and assessed the effect of an abrocitinib dose increase on platelet counts. Methods Analysis included the phase 3 trials JADE MONO-1 (NCT03349060), MONO-2 (NCT03575871), COMPARE (NCT03720470), and TEEN (NCT03796676). For platelet counts and simulations, a phase 2 psoriasis trial (NCT02201524) and phase 2b (NCT02780167) and phase 3 (MONO-1, MONO-2, and REGIMEN (NCT03627767)) abrocitinib trials were pooled. A training-and-validation framework assessed potential predictors of response at week 4: score and score change from baseline in the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), and Peak Pruritus Numerical Rating Scale (PP-NRS), and percentage change from baseline in EASI. The dependent variables at week 12 were ≥ 75% improvement in EASI (EASI-75) and IGA score of 0 (clear) or 1 (almost clear) and ≥ 2-point improvement from baseline. The probability of each variable to predict week 12 EASI-75 and IGA responses was calculated. Results In the training cohort (n = 453), 72% of the ≥ 50% improvement in EASI (EASI-50) at week 4 responders and 16% of the nonresponders with abrocitinib 100 mg achieved EASI-75 at week 12; 48% and 6% of the week 4 EASI-50 responders and nonresponders, respectively, achieved week 12 IGA response. Similar results occurred with week 4 IGA = 2, ≥ 4-point improvement from baseline in PP-NRS, or EASI = 8 responders/nonresponders. Platelet counts after an abrocitinib dose increase from 100 to 200 mg were similar to those seen with continuous dosing with abrocitinib 100 mg or 200 mg. Conclusion Achieving week 4 clinical responses with abrocitinib 100 mg may be useful in predicting week 12 responses. Week 4 nonresponders may benefit from a dose increase to abrocitinib 200 mg, and those that receive this dose increase are likely to achieve treatment success at week 12, with no significant impact on platelet count recovery. Video abstract available for this article. Clinical Trial Registration NCT03349060, NCT03575871, NCT03720470, NCT03796676, NCT02201524, NCT02780167 and NCT03627767.

Flexible piezoresistive strain sensors have received significant attention due to their diverse applications in monitoring human activities and health, as well as in robotics, prosthetics, and human–computer interaction interfaces. Among the various flexible sensor types, those with microstructure designs are considered promising for strain sensing due to their simple structure, high sensitivity, extensive operational range, rapid response time, and robust stability. This review provides a concise overview of recent advancements in flexible piezoresistive sensors based on microstructure design for enhanced strain sensing performance, including the impact of microstructure on sensing mechanisms, classification of microstructure designs, fabrication methods, and practical applications. Initially, this review delves into the analysis of piezoresistive sensor sensing mechanisms and performance parameters, exploring the relationship between microstructure design and performance enhancement. Subsequently, an in-depth discussion is presented, focusing on the primary themes of microstructure design classification, process selection, performance characteristics, and specific applications. This review employs mathematical modeling and hierarchical analysis to emphasize the directionality of different microstructures on performance enhancement and to highlight the performance advantages and applicable features of various microstructure types. In conclusion, this review examines the multifunctionality of flexible piezoresistive sensors based on microstructure design and addresses the challenges that still need to be overcome and improved, such as achieving a wide range of stretchability, high sensitivity, and robust stability. This review summarizes the research directions for enhancing sensing performance through microstructure design, aiming to assist in the advancement of flexible piezoresistive sensors.

Abstract Background IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines. Case presentation : A 77-year-old woman was admitted with a jaw mass and nausea and vomiting. Laboratory tests showed elevated serum IgG4, pituitary MRI suggested thickening of the pituitary stalk, and head and neck CT suggested orbital and mandibular masses. Patients with mandibular mass were diagnosed with Mikulicz’s disease with IgG4-related hypophysitis. We found no other evidence of causing thickening of the pituitary stalk. She was given oral prednisolone 30 mg daily, and her nausea and vomiting improved significantly, and the mandibular and ocular masses decreased in size. Conclusion Mikulicz’s disease combined with IgG4-related hypophysitis is a rare case of IgG4-RD in elderly women. IgG4-RD is one of the causes of head and neck exocrine gland mass and pituitary stalk thickening in the elderly.

Abstract Background Carotid endarterectomy (CEA) is a surgical procedure that can reduce the risk of stroke in patients with carotid artery stenosis. However, controversy still exists regarding the optimal surgical technique for CEA. Objective To compare the safety and effectiveness of different techniques. Methods Data on baseline characteristics as well as perioperative and postoperative complications from patients who underwent CEA at the Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, were retrospectively collected and analyzed. Results A total of 262 CEA patients included in study, with a total of 265 CEA operations. The mean age of 69.95 ± 7.29 (range, 44–89) years. 65 (24.5%) patients underwent cCEA, 94 (35.5%) underwent pCEA, and 106 (40.0%) underwent eCEA. The use of shunt (1.9%) and the mean operation time were lower in eCEA group (P

Abstract Objective A novel Proximal Femoral Bionic Nail (PFBN) has been developed by a research team for the treatment of femoral neck fractures. This study aims to compare the biomechanical properties of the innovative PFBN with those of the conventional Inverted Triangular Cannulated Screw (ITCS) fixation method through biomechanical testing. Methods Sixteen male femoral specimens preserved in formalin were selected, with the donors’ age at death averaging 56.1 ± 6.3 years (range 47–64 years), and a mean age of 51.4 years. The femurs showed no visible damage and were examined by X-rays to exclude diseases affecting bone quality such as tumors, severe osteoporosis, and deformities. The 16 femoral specimens were randomly divided into an experimental group (n = 8) and a control group (n = 8). All femurs were prepared with Pauwels type III femoral neck fractures, fixed with PFBN in the experimental group and ITCS in the control group. Displacement and stress limits of each specimen were measured through cyclic compression tests and failure experiments, and vertical displacement and strain values under a 600 N vertical load were measured in all specimens through vertical compression tests. Results In the vertical compression test, the average displacement at the anterior head region of the femur was 0.362 mm for the PFBN group, significantly less than the 0.480 mm for the ITCS group (p

Abstract Background Plant height (PH) is an important agronomic trait influenced by a complex genetic network. However, the genetic basis for the variation in PH in Medicago sativa remains largely unknown. In this study, a comprehensive genome-wide association analysis was performed to identify genomic regions associated with PH using a diverse panel of 220 accessions of M. sativa worldwide. Results Our study identified eight novel single nucleotide polymorphisms (SNPs) significantly associated with PH evaluated in five environments, explaining 8.59–12.27% of the phenotypic variance. Among these SNPs, the favorable genotype of chr6__31716285 had a low frequency of 16.4%. Msa0882400, located proximal to this SNP, was annotated as phosphate transporter 3;1, and its role in regulating alfalfa PH was supported by transcriptome and candidate gene association analysis. In addition, 21 candidate genes were annotated within the associated regions that are involved in various biological processes related to plant growth and development. Conclusions Our findings provide new molecular markers for marker-assisted selection in M. sativa breeding programs. Furthermore, this study enhances our understanding of the underlying genetic and molecular mechanisms governing PH variations in M. sativa.

Abstract Aiming at the problem of image classification with insignificant morphological structural features, strong target correlation, and low signal-to-noise ratio, combined with prior feature knowledge embedding, a deep learning method based on ResNet and Radial Basis Probabilistic Neural Network (RBPNN) is proposed model. Taking ResNet50 as a visual modeling network, it uses feature pyramid and self-attention mechanism to extract appearance and semantic features of images at multiple scales, and associate and enhance local and global features. Taking into account the diversity of category features, channel cosine similarity attention and dynamic C-means clustering algorithms are used to select representative sample features in different category of sample subsets to implicitly express prior category feature knowledge, and use them as the kernel centers of radial basis probability neurons (RBPN) to realize the embedding of diverse prior feature knowledge. In the RBPNN pattern aggregation layer, the outputs of RBPN are selectively summed according to the category of the kernel center, that is, the subcategory features are combined into category features, and finally the image classification is implemented based on Softmax. The functional module of the proposed method is designed specifically for image characteristics, which can highlight the significance of local and structural features of the image, form a non-convex decision-making area, and reduce the requirements for the completeness of the sample set. Applying the proposed method to medical image classification, experiments were conducted based on the brain tumor MRI image classification public dataset and the actual cardiac ultrasound image dataset, and the accuracy rate reached 85.82% and 83.92% respectively. Compared with the three mainstream image classification models, the performance indicators of this method have been significantly improved.

Abstract Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function. CD8 + T cells show higher oligoclonality than CD4 + T cells, with the largest synovial clones enriched in GZMK+ cells. CD8 + T cells with possibly virus-reactive TCRs are distributed across transcriptomic clusters. In the B cell compartment, NR4A1+ activated B cells, and plasma cells are enriched in the synovium and demonstrate substantial clonal expansion. We identify synovial plasma cells that share BCRs with synovial ABC, memory, and activated B cells. Receptor-ligand analysis predicted IFNG and TNFRSF members as mediators of synovial Tph-B cell interactions. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate the synovium of patients with RA.

Abstract Background N6-methyladenosine (m6A) methylation is a prevalent RNA modification implicated in various diseases. However, its role in intervertebral disc degeneration (IDD), a common cause of low back pain, remains unclear. Results In this investigation, we explored the involvement of m6A demethylation in the pathogenesis of IDD. Our findings revealed that ALKBH5 (alkylated DNA repair protein AlkB homolog 5), an m6A demethylase, exhibited upregulation in degenerative discs upon mild inflammatory stimulation. ALKBH5 facilitated m6A demethylation within the three prime untranslated region (3′-UTR) of Runx2 mRNA, consequently enhancing its mRNA stability in a YTHDF1 (YTH N6-methyladenosine RNA binding protein F1)-dependent manner. The subsequent elevation in Runx2 expression instigated the upregulation of ADAMTSs and MMPs, pivotal proteases implicated in extracellular matrix (ECM) degradation and IDD progression. In murine models, subcutaneous administration of recombinant Runx2 protein proximal to the lumbar disc in mice elicited complete degradation of intervertebral discs (IVDs). Injection of recombinant MMP1a and ADAMTS10 proteins individually induced mild to moderate degeneration of the IVDs, while co-administration of MMP1a and ADAMTS10 resulted in moderate to severe degeneration. Notably, concurrent injection of the Runx2 inhibitor CADD522 with recombinant Runx2 protein did not result in IVD degeneration in mice. Furthermore, genetic knockout of ALKBH5 and overexpression of YTHDF1 in mice, along with lipopolysaccharide (LPS) treatment to induce inflammation, did not alter the expression of Runx2, MMPs, and ADAMTSs, and no degeneration of the IVDs was observed. Conclusion Our study elucidates the role of ALKBH5-mediated m6A demethylation of Runx2 mRNA in activating MMPs and ADAMTSs, thereby facilitating ECM degradation and promoting the occurrence of IDD. Our findings suggest that targeting the ALKBH5/Runx2/MMPs/ADAMTSs axis may represent a promising therapeutic strategy for preventing IDD.

Abstract Cuproptosis is a newly defined form of programmed cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis and metastasis. However, whether cuproptosis-related lncRNAs are involved in the pathogenesis of diffuse large B cell lymphoma (DLBCL) remains unclear. This study aimed to identify the prognostic signatures of cuproptosis-related lncRNAs in DLBCL and investigate their potential molecular functions. RNA-Seq data and clinical information for DLBCL were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Cuproptosis-related lncRNAs were screened out through Pearson correlation analysis. Utilizing univariate Cox, least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analysis, we identified seven cuproptosis-related lncRNAs and developed a risk prediction model to evaluate its prognostic value across multiple groups. GO and KEGG functional analyses, single-sample GSEA (ssGSEA), and the ESTIMATE algorithm were used to analyze the mechanisms and immune status between the different risk groups. Additionally, drug sensitivity analysis identified drugs with potential efficacy in DLBCL. Finally, the protein–protein interaction (PPI) network were constructed based on the weighted gene co-expression network analysis (WGCNA). We identified a set of seven cuproptosis-related lncRNAs including LINC00294, RNF139-AS1, LINC00654, WWC2-AS2, LINC00661, LINC01165 and LINC01398, based on which we constructed a risk model for DLBCL. The high-risk group was associated with shorter survival time than the low-risk group, and the signature-based risk score demonstrated superior prognostic ability for DLBCL patients compared to traditional clinical features. By analyzing the immune landscapes between two groups, we found that immunosuppressive cell types were significantly increased in high-risk DLBCL group. Moreover, functional enrichment analysis highlighted the association of differentially expressed genes with metabolic, inflammatory and immune-related pathways in DLBCL patients. We also found that the high-risk group showed more sensitivity to vinorelbine and pyrimethamine. A cuproptosis-related lncRNA signature was established to predict the prognosis and provide insights into potential therapeutic strategies for DLBCL patients.

Abstract Developing highly active materials that efficiently utilize solar spectra is crucial for photocatalysis, but still remains a challenge. Here, we report a new donor-acceptor (D-A) covalent organic framework (COF) with a wide absorption range from 200 nm to 900 nm (ultraviolet-visible-near infrared light). We find that the thiophene functional group is accurately introduced into the electron acceptor units of TpDPP-Py (TpDPP: 5,5’-(2,5-bis(2-ethylhexyl)−3,6-dioxo-2,3,5,6-tetrahydropyrrolo [3,4-c]pyrrole-1,4-diyl)bis(thiophene-2-carbaldehyde), Py: 1,3,6,8-tetrakis(4-aminophenyl)pyrene) COFs not only significantly extends its spectral absorption capacity but also endows them with two-photon and three-photon absorption effects, greatly enhancing the utilization rate of sunlight. The selective coupling of benzylamine as the target reactant is used to assess the photocatalytic activity of TpDPP-Py COFs, showing high photocatalytic conversion of 99% and selectivity of 98% in 20 min. Additionally, the TpDPP-Py COFs also exhibit the universality of photocatalytic selective coupling of other imine derivatives with ~100% conversion efficiency. Overall, this work brings a significant strategy for developing COFs with a wide absorption range to enhance photocatalytic activity.

Abstract Magnetoelectric materials, which encompass coupled magnetic and electric polarizabilities within a single phase, hold great promises for magnetic controlled electronic components or electric-field controlled spintronics. However, the realization of ideal magnetoelectric materials remains tough due to the inborn competion between ferroelectricity and magnetism in both levels of symmetry and electronic structure. Herein, we introduce a methodology for constructing single phase paramagnetic ferroelectric molecule [TMCM][FeCl4], which shows low-magnetic-field magnetoelectricity at room temperature. By applying a low magnetic field (≤1 kOe), the halogen Cl‧‧‧Cl distance and the volume of [FeCl4]− anions could be manipulated. This structural change causes a characteristic magnetostriction hysteresis, resulting in a substantial deformation of ~10−4 along the a-axis under an in-plane magnetic field of 2 kOe. The magnetostrictive effect is further qualitatively simulated by density functional theory calculations. Furthermore, this mechanical deformation significantly dampens the ferroelectric polarization by directly influencing the overall dipole configuration. As a result, it induces a remarkable α 31 component (~89 mV Oe−1 cm−1) of the magnetoelectric tensor. And the magnetoelectric coupling, characterized by the change of polarization, reaches ~12% under 40 kOe magnetic field. Our results exemplify a design methodology that enables the creation of room-temperature magnetoelectrics by leveraging the potent effects of magnetostriction.

Background NFE2L2 (nuclear factor erythroid-2-related factor-2) encodes a basic leucine zipper (bZIP) transcription factor and exhibits variations in various tumor types, including lung cancer. In this study, we comprehensively investigated the impact of simultaneous mutations on the survival of NFE2L2-mutant lung cancer patients within specific subgroups.

A significant proportion of the world's population is currently experiencing heat stress. This results from the effects of global warming, urban heat islands (UHIs), and the growth of urban populations. Researchers have investigated multiple strategies to address this problem. It has been found that the outdoor thermal environment (OTE) can be modified by means of vegetation, water surfaces, and urban geometry. Several studies have indicated that certain geometric factors have demonstrated a higher degree of effectiveness in cooling the surrounding environment. OTE studies often employ two commonly utilised factors, known as urban geometry indicating parameters (UGPs)—the sky view factor (SVF) and height-to-width ratio (H/W). This article compares OTE studies focusing on these two factors. The comparison encompasses characteristics such as study methods, places and times of conducting, and thermal indices. The findings indicate that geometric studies have primarily relied on simulation and field measurement methods. These studies were predominantly conducted in tropical or subtropical cities during warm seasons, with a preference for daytime investigations. Complex thermal indices, including the physiologically equivalent temperature and mean radiant temperature, were commonly employed. In addition to UGPs, other physical factors, such as orientation, were also taken into consideration. Studies on H/W and SVF differed slightly although they are both geometrically indicative. This review can provide guidance for future studies in the field of urban geometry, in that researchers may choose to prioritise the examination of practical indicators, such as the energy load, to conduct a more comprehensive analysis while also taking into account other physical aspects, such as the presence of trees.

TiO2–Y2O3–ZrO2 composite ceramics exhibit excellent abrasion resistance, corrosion resistance, and high-temperature resistance, making them vital structural-functional materials in ceramics and refractories. The key to preparing high-quality TiO2–Y2O3–ZrO2 ceramic powders lies in controlling the agglomeration rate, which can be optimized by choosing an appropriate drying method. This study utilized microwave drying techniques to dehydrate TiO2–Y2O3–ZrO2 ceramic powders. It was found that the average drying rate is proportional to initial masses, initial moisture contents and microwave heating powers. To describe the drying process, four models—the Quadratic, Wang and Singh, Modified Page, and Page—were employed. The best model for the drying process was the Modified Page model. The specimens were analyzed to assess the alterations in the samples pre and post-drying by scanning electron microscopy and Fourier transform infrared spectroscopy. The findings revealed that microwaves can hasten the drying process of TiO2–Y2O3–ZrO2 and enhance its spread. Utilizing Fick's second law, the effective diffusion coefficient was ascertained, showing an inverse proportionality to the sample mass, and a proportionality to the microwave heating power and initial moisture content. Using the Arrhenius exponential model, it was ascertained that the microwave drying process's activation energy stands at 13.81834 W/g. This paper demonstrates that microwave drying effectively achieves efficient drying and lays the theoretical and experimental groundwork for the microwave heating and drying of other powdered materials.