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Guojun Zhang,1 Chuan Yang,2 Caixia Zhao,1 Feng Xian,3 Dong Qing,1 Qiyu Guo,1 Junmei Song,1 Xilin Liu,1 Jun Bie1 1Department of Oncology, Nanchong Central Hospital and The Second Clinical Medical College of North Sichuan Medical College, Nanchong, People’s Republic of China; 2Department of Oncology, Guangyuan Central Hospital, Guangyuan, People’s Republic of China; 3School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of ChinaCorrespondence: Jun Bie, Department of Oncology, Nanchong Central Hospital and The Second Clinical Medical College of North Sichuan Medical College, Hongguang Road, Shunqing District, Nanchong, People’s Republic of China, Email 78593860@qq.comBackground: The neutrophil-to-lymphocyte ratio (NLR) has been shown to have prognostic value in several common cancers. This study aimed to investigate the prognostic value of NLR in patients with advanced oesophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy (dCRT).Methods: A retrospective analysis was performed on 158 patients with advanced ESCC who received dCRT from January 2012 to December 2018. The NLR for different treatment stages was calculated based on laboratory test results. The Kaplan–Meier (KM) method and Cox proportional regression model were used to analyse the relationship between NLR and overall survival (OS).Results: The mean NLR of 158 patients with ESCC was 3.403 ± 2.479. The pre-treatment NLR cut-off was 4.839, and patients were divided into the low NLR group (NLR < 4.839) and the high NLR group (NLR ≥ 4.839). NLR in patients with ESCC was related to N stage (P < 0.05). The KM analysis showed that the median OS of all enrolled patients was 29.3 months, the median OS periods of patients in the high and low NLR groups were 15.6 and 35.8 months, respectively, and the OS of the low NLR group was better than that of the high NLR group (P < 0.001). In the multivariate analysis, NLR was an independent prognostic factor that affects the prognosis of patients with ESCC receiving dCRT. Furthermore, patients who maintained a high NLR before and after treatment showed worse clinical outcomes than the other groups.Conclusion: Our findings suggest that NLR can effectively assess the prognosis of patients with advanced ESCC undergoing dCRT.Graphical Abstract: Keywords: oesophageal squamous cell carcinoma, radiochemotherapy, neutrophil-to-lymphocyte ratio

Defeng Qing,1,* Yuying Wu,2,* Xu Liu,1,* Hailan Jiang,1,* Chaohua Zhu,1,* Pei Liu,3 Junming Dang,4 Xianglong Li,1 Zhaohong Chen,1 Xianfeng Long,1 Qiang Pang,1 Luxing Peng,1 Shan Deng,1 Junzhao Gu,1 Renfeng Zhao,2 Changyi Chen,2 Heming Lu1 1Department of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, People’s Republic of China; 2Department of Gynecology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, People’s Republic of China; 3Department of Radiation Oncology, Youjiang Medical University for Nationalities, Baise 533000, People’s Republic of China; 4Department of Oncology, Guangxi University of Chinese Medicine, Nanning 530001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Heming LuDepartment of Radiation Oncology, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City 530021, People’s Republic of ChinaTel +86-771-218-6504Email luhming3632@163.comPurpose: We aimed to evaluate the long-term survival outcomes of concurrent chemoradiotherapy (CCRT) combined with nimotuzumab followed by surgery in patients with locally advanced cervical cancer (LACC).Patients and Methods: Patients received whole pelvic intensity-modulated radiation therapy (IMRT) and concomitantly with weekly cisplatin (40 mg/m2) or nedaplatin (30 mg/m2) and weekly nimotuzumab (200 mg). After assessment of the treatment response, patients then underwent radical surgery.Results: Between June 2013 and July 2016, 33 patients with FIGO IB2–IIIB cervical cancer were recruited. Clinical complete response and partial response were observed in 8 (24.3%) and 23 patients (69.7%), respectively. Twenty-seven patients (81.8%) were successfully treated with radical hysterectomy and pelvic lymphadenectomy: 9 (33.3%) showed pathological complete response; 10 (37.1%) showed partial response and 8 (29.6%) presented with persistent macroscopic/microscopic residual carcinoma. For the intention-to-treat population, the median follow-up time was 53.7 months. Locoregional recurrence and distant metastases were observed in three and seven patients, respectively. The 5-year overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival were 81.5%, 72.7%, 90.9%, and 78.3%, respectively. Both acute and late toxicities were manageable and mainly limited to grade 1 or 2.Conclusion: Concurrent chemoradiotherapy combined with nimotuzumab followed by surgery for patients with LACC is safe and results in excellent long-term treatment outcomes. Further randomized controlled studies are warranted to confirm the findings.Keywords: locally advanced cervical cancer, neoadjuvant chemotherapy, intensity-modulated radiotherapy, anti-EGFR monoclonal antibody, radical surgery

Abstract Laser-lubricant interaction has been a critical reliability issue in a thermo-tribological system named heat-assisted magnetic recording, one of the next generation hard disk drive solutions to increasing data storage. The lubricant response under laser irradiation and the subsequent lubricant recovery are crucial to the system’s reliability and longevity, however, they cannot be diagnosed locally and timely so far. Here, we propose a thermal scheme to in-situ characterize the mechanical laser-lubricant interaction. The nanometer-thick lubricant has a thermal barrier effect on the near-field thermal transport in the system, according to which the lubricant thickness can be determined. As demonstrations, this paper reports the first quantitative in-situ measurements of the laser-induced lubricant depletion and the subsequent reflow dynamics. The proposed scheme shows a sub-angstrom resolution (~0.2 Å) and a fast response time within seconds, rendering in-situ real-time lubricant diagnosis feasible in the practical hard disk drive products.

Abstract Aims The Selvester scoring system has been derived from ECG parameters for estimating infarct size. However, there is still a lack of evidence for Selvester score as an alternative to cardiac magnetic resonance (CMR) myocardial injury makers for risk stratification and prediction of left ventricular function (LVF) recovery among patients with ST‐segment elevation myocardial infarction (STEMI). Methods and results This multicentre observational study enrolled 328 STEMI patients (88.4% men, 57.3 ± 10.6 years of age) undergoing CMR examination 1 week post‐reperfusion therapy. Patients with baseline left ventricular ejection fraction (LVEF) 0.05). A Selvester score >10 doubled the risk of MACEs in patients with systolic dysfunction (1.91 [1.02 to 3.58], P = 0.04). Additionally, Selvester score, baseline LVEF, transmural infarction, and peak CK‐MB were independent predictors of recovered LVF, with Selvester score providing incremental predictive value to peak CK‐MB in predicting recovered LVF (∆AUC = 0.07, P

Abstract Electromagnetic fields (EMFs) have emerged as an effective treatment for osteoporosis. However, the specific mechanism underlying their therapeutic efficacy remains controversial. Herein, we confirm the pro-osteogenic effects of 15 Hz and 0.4-1 mT low-frequency sinusoidal EMFs (SEMFs) on rat bone marrow mesenchymal stem cells (BMSCs). Subsequent miRNA sequencing reveal that miR-34b-5p is downregulated in both the 0.4 mT and 1 mT SEMFs-stimulated groups. To clarify the role of miR-34b-5p in osteogenesis, BMSCs are transfected separately with miR-34b-5p mimic and inhibitor. The results indicate that miR-34b-5p mimic transfection suppress osteogenic differentiation, whereas inhibition of miR-34b-5p promote osteogenic differentiation of BMSCs. In vivo assessments using microcomputed tomography, H&E staining, and Masson staining show that miR-34b-5p inhibitor injections alleviate bone mass loss and trabecular microstructure deterioration in ovariectomy (OVX) rats. Further validation demonstrates that miR-34b-5p exerts its effects by regulating STAC2 expression. Modulating the miR-34b-5p/STAC2 axis attenuate the pro-osteogenic effects of low-frequency SEMFs on BMSCs. These studies indicate that the pro-osteogenic effect of SEMFs is partly due to the regulation of the miR-34b-5p/STAC2 pathway, which provides a potential therapeutic candidate for osteoporosis.

Abstract Background The type II based CRISPR-Cas system remains restrictedly utilized in archaea, a featured domain of life that ranks parallelly with Bacteria and Eukaryotes. Methanococcus maripaludis, known for rapid growth and genetic tractability, serves as an exemplary model for studying archaeal biology and exploring CO2−based biotechnological applications. However, tools for controlled gene regulation remain deficient and CRISPR-Cas tools still need improved in this archaeon, limiting its application as an archaeal model cellular factory. Results This study not only improved the CRISPR-Cas9 system for optimizing multiplex genome editing and CRISPR plasmid construction efficiencies but also pioneered an effective CRISPR interference (CRISPRi) system for controlled gene regulation in M. maripaludis. We developed two novel strategies for balanced expression of multiple sgRNAs, facilitating efficient multiplex genome editing. We also engineered a strain expressing Cas9 genomically, which simplified the CRISPR plasmid construction and facilitated more efficient genome modifications, including markerless and scarless gene knock-in. Importantly, we established a CRISPRi system using catalytic inactive dCas9, achieving up to 100-fold repression on target gene. Here, sgRNAs targeting near and downstream regions of the transcription start site and the 5′end ORF achieved the highest repression efficacy. Furthermore, we developed an inducible CRISPRi-dCas9 system based on TetR/tetO platform. This facilitated the inducible gene repression, especially for essential genes. Conclusions Therefore, these advancements not only expand the toolkit for genetic manipulation but also bridge methodological gaps for controlled gene regulation, especially for essential genes, in M. maripaludis. The robust toolkit developed here paves the way for applying M. maripaludis as a vital model archaeal cell factory, facilitating fundamental biological studies and applied biotechnology development of archaea.

Abstract Recent studies have suggested that mRNA internal m7G and its writer protein METTL1 are closely related to cell metabolism and cancer regulation. Here, we identify that IGF2BP family proteins IGF2BP1-3 can preferentially bind internal mRNA m7G. Such interactions, especially IGF2BP3 with m7G, could promote the degradation of m7G target transcripts in cancer cells. IGF2BP3 is more responsive to changes of m7G modification, while IGF2BP1 prefers m6A to stabilize the bound transcripts. We also demonstrate that p53 transcript, TP53, is m7G-modified at its 3’UTR in cancer cells. In glioblastoma, the methylation level and the half lifetime of the modified transcript could be modulated by tuning IGF2BP3, or by site-specific targeting of m7G through a dCas13b-guided system, resulting in modulation of cancer progression and chemosensitivity.

Abstract Background Hepatocellular carcinoma (HCC) constitutes an important contributor to fatalities. Coronavirus disease 2019 (COVID-19) frequently presents with complications such as respiratory distress, systemic inflammatory responses, and damage to various organs. Several studies have investigated the relationship between COVID-19 and mortality in patients with liver cancer, but there are few research on the relationship between them. This study is to explore the correlation between the two diseases and drugs treating them. Methods The Gene Expression Omnibus (GEO) database provides gene datasets of COVID-19 patients and HCC patients. Through differential gene analysis and weighted gene co-expression network analysis, we determined 223 genes represented in HCC and COVID-19. We then used functional annotation, protein–protein interaction network construction, predictive model development and verification, prognostic value analysis, and miRNA–gene network construction. Besides, we created a drug–hub–gene network by predicting possible medications that interact with hub genes using the Drug–Gene Interaction Database (DGIdb). Ultimately, we applied immunohistochemistry to ascertain the hub genes expression. Results This study revealed that eight core genes (RRM2, TPX2, DTL, CDT1, TYMS, CDCA5, CDC25C, and HJURP) co-existed in both HCC and COVID-19 and were differentially expressed in both HCC and normal tissues.CDC25C, RRM2, CDCA5, and HJURP had diagnostic value (AUC > 0.8) and prognostic value (adjusted P-value

Abstract Polyamorphic transition (PT) is a compelling and pivotal physical phenomenon in the field of glass and materials science. Understanding this transition is of scientific and technological significance, as it offers an important pathway for effectively tuning the structure and property of glasses. In contrast to the PT observed in conventional metallic glasses (MGs), which typically exhibit a pronounced first-order nature, herein we report a continuous PT (CPT) without first-order characteristics in high-entropy MGs (HEMGs) upon heating. This CPT behavior is featured by the continuous structural evolution at the atomic level and an increasing chemical concentration gradient with temperature, but no abrupt reduction in volume and energy. The continuous transformation is associated with the absence of local favorable structures and chemical heterogeneity caused by the high configurational entropy, which limits the distance and frequency of atomic diffusion. As a result of the CPT, numerous glass states can be generated, which provides an opportunity to understand the nature, atomic packing, formability, and properties of MGs. Moreover, this discovery highlights the implication of configurational entropy in exploring polyamorphic glasses with an identical composition but highly tunable structures and properties.

Abstract Aims/Introduction Our aim was to investigate the optimal fasting glucose (FPG) range in Chinese older adults with type 2 diabetes, and to clarify whether the optimal range varies according to the control of risk factors. Materials and Methods The baseline survey for the cohort study began in 2018, with follow up ending in 2022. Our study enrolled 59,030 older diabetes patients with no history of cardiovascular disease (CVD). Participants were divided into nine groups based on their baseline glycemic status. The association between FPG and the risk of adverse outcomes was mainly estimated by multivariate Cox proportional risk models and restricted spline analysis. Results During the 4‐year follow‐up period, a total of 5,637 deaths and 4,904 CVD events occurred. The associations of FPG with mortality and CVD events showed J‐shaped curves. Among all‐cause deaths, the hazard ratios for FPG ≤4.50 and >11.50 mmol/L were 1.50 (95% confidence interval [CI] 1.31–1.71) and 1.84 (95% CI 1.67–2.02). Among CVD, the hazard ratios for FPG ≤4.50 and >11.50 mmol/L were 1.31 (95% CI 1.13–1.53) and 1.71 (95% CI 1.54–1.89), respectively. The optimal FPG ranges of all‐cause mortality and CVD were 5.50–7.50 and 4.50–7.50 mmol/L, respectively. For participants with at least two risk factors, the optimal FPG levels were higher than those with fewer risk factors. Conclusions In older Chinese diabetes patients, the FPG ranges related to the minimum death and CVD event rates were 5.50–7.50 and 4.50–7.50 mmol/L, respectively. Patients with more cardiovascular risk factors had higher optimal blood glucose ranges than those with fewer risk factors.

CO2 storage in basalt formation has received much attention as one of the new CO2 geological storage methods worldwide. It has been successfully implemented in Iceland and the United States. During the process of carbon storage in basalt, CO2 is transformed into solid minerals, which differs significantly from carbon storage in sandstone reservoirs in terms of CO2 injection method, burial depth, and physical property requirements of reservoir cap. Significant differences are also found in both monitoring schemes. By studying the Wallula basalt storage project in the United States and the Carbfix mineralization storage project in Iceland, this study compared and summarized the monitoring schemes of basalt storage for different CO2 injection phases (supercritical and gas dissolved state). The monitoring systems of basalt storage, saline aquifer storage, oil and gas reservoir storage were further compared. The storage monitoring system for sandstone reservoir focuses on the structural integrity of the CO2 reservoir and evaluating the change of CO2 concentration along the potential leakage path. The monitoring period is usually more than 50 years. In contrast, basalt mineralization and storage technology focus on the mineralization reaction of “water-CO2-basalt”. Its monitoring system is mainly to describe the property changing pattern of each substance from downhole fluid (chemical compositions, tracer concentrations, pH, etc.) during the storage cycle. Moreover, it evaluates the degree of mineralization reaction and the storage efficiency of basalt qualitatively and quantitatively. Finally, based on the systematic and comprehensive monitoring scheme of saline aquifer and oil and gas reservoir storage, the basalt-CO2 mineralization storage monitoring technology is analyzed systematically and a complete set of basalt-CO2 mineralization storage monitoring scheme and process is summarized. By comparing different CO2 storage monitoring systems, this study proposes a universal “subsurface-wellbore-surface-ground” monitoring scheme for basalt-CO2 mineralization: monitoring scope, purpose, program, and alert system. This provides basic information for the future basalt-CO2 mineralization storage demonstration project.

Abstract Efficient thrombolysis in time is crucial for prognostic improvement of patients with acute arterial thromboembolic disease, while limitations and complications still exist in conventional thrombolytic treatment methods. Herein, our study sought to investigate a novel dual-mode strategy that integrated ultrasound (US) and near-infrared light (NIR) with establishment of hollow mesoporous silica nanoprobe (HMSN) which contains Arginine-glycine-aspartate (RGD) peptide (thrombus targeting), perfluoropentane (PFP) (thrombolysis with phase-change and stable cavitation) and indocyanine green (ICG) (thrombolysis with photothermal conversion). HMSN is used as the carrier, the surface is coupled with targeted RGD to achieve high targeting and permeability of thrombus, PFP and ICG are loaded to achieve the collaborative diagnosis and treatment of thrombus by US and NIR, so as to provide a new strategy for the integration of diagnosis and treatment of arterial thrombus. From the in vitro and in vivo evaluation, RGD/ICG/PFP@HMSN can aggregate and penetrate at the site of thrombus, and finally establish the dual-mode directional development and thrombolytic treatment under the synergistic effect of US and NIR, providing strong technical support for the accurate diagnosis and treatment of arterial thrombosis. Graphical Abstract

Abstract Background An accurate and non-invasive approach is urgently needed to distinguish tuberculosis granulomas from lung adenocarcinomas. This study aimed to develop and validate a nomogram based on contrast enhanced-compute tomography (CE-CT) to preoperatively differentiate tuberculosis granuloma from lung adenocarcinoma appearing as solitary pulmonary solid nodules (SPSN). Methods This retrospective study analyzed 143 patients with lung adenocarcinoma (mean age: 62.4 ± 6.5 years; 54.5% female) and 137 patients with tuberculosis granulomas (mean age: 54.7 ± 8.2 years; 29.2% female) from two centers between March 2015 and June 2020. The training and internal validation cohorts included 161 and 69 patients (7:3 ratio) from center No.1, respectively. The external testing cohort included 50 patients from center No.2. Clinical factors and conventional radiological characteristics were analyzed to build independent predictors. Radiomics features were extracted from each CT-volume of interest (VOI). Feature selection was performed using univariate and multivariate logistic regression analysis, as well as the least absolute shrinkage and selection operator (LASSO) method. A clinical model was constructed with clinical factors and radiological findings. Individualized radiomics nomograms incorporating clinical data and radiomics signature were established to validate the clinical usefulness. The diagnostic performance was assessed using the receiver operating characteristic (ROC) curve analysis with the area under the receiver operating characteristic curve (AUC). Results One clinical factor (CA125), one radiological characteristic (enhanced-CT value) and nine radiomics features were found to be independent predictors, which were used to establish the radiomics nomogram. The nomogram demonstrated better diagnostic efficacy than any single model, with respective AUC, accuracy, sensitivity, and specificity of 0.903, 0.857, 0.901, and 0.807 in the training cohort; 0.933, 0.884, 0.893, and 0.892 in the internal validation cohort; 0.914, 0.800, 0.937, and 0.735 in the external test cohort. The calibration curve showed a good agreement between prediction probability and actual clinical findings. Conclusion The nomogram incorporating clinical factors, radiological characteristics and radiomics signature provides additional value in distinguishing tuberculosis granuloma from lung adenocarcinoma in patients with a SPSN, potentially serving as a robust diagnostic strategy in clinical practice.

Abstract Understanding the ice nucleation mechanism in the catalyst layers (CLs) of proton exchange membrane (PEM) fuel cells and inhibiting icing by designing the CLs can optimize the cold start strategies, which can enhance the performance of PEM fuel cells. Herein, mitigating the structural matching and templating effects by adjusting the surface morphology and wettability can inhibit icing on the platinum (Pt) catalyst surface effectively. The Pt(211) surface can inhibit icing because the atomic spacing of (211) crystalline surface is much larger than the characteristic distance of ice crystal, thereby mitigating the structural matching effects. A water overlayer on the Pt surface induced by the strong attraction of Pt can act as a template for ice layers and plays an important role in the icing process. Buckling of water overlayer due to the larger atomic spacing of (211) crystalline surface mitigates the templating effect and inhibits icing. Moreover, the water overlayer on the hydrophobic Pt(211) surface with fewer water molecules also mitigates the templating effect, which makes ice nucleation more difficult than homogeneous nucleation. These findings reveal the ice nucleation mechanisms on the Pt catalyst surface from the molecular level and are valuable for catalyst designs to inhibit icing in CL.

The flow field serves as an important component of proton exchange membrane fuel cells (PEMFCs) for maintaining the hydration of the membrane and discharge of excessive water. In this study, a transparent polycarbonate plate was used as the cathode end plate of the PEMFC. The water management capacity of the PEMFCs with different cathode flow fields was evaluated. The movement and evolution patterns of water droplets, film, and columns in different flow fields were analyzed. The results show that liquid water is discharged faster as the cross-section of the flow channel becomes smaller. The performance of the PEMFC with a partially-narrowed flow field is higher due to better water management capacity and forced convection of gas reactant. Liquid water exists mostly in the form of liquid columns in the parallel flow channel, damaging the uniformity of gas distribution. The wavy flow field is likely to be flooded due to the difference of water movement velocity in different channel regions. In addition, a volume of fluid (VOF) model was developed to quantitatively evaluate the water management performance of each type of flow field. The water movement patterns in the different flow channels were concluded. This study provided real-time observations of water movement in the flow channel, revealing a correlation between water management capabilities and the performance of the PEMFC.

Abstract Silk nanofibrils (SNFs), the fundamental building blocks of silk fibers, endow them with exceptional properties. However, the intricate mechanism governing SNF assembly, a process involving both protein conformational transitions and protein molecule conjunctions, remains elusive. This lack of understanding has hindered the development of artificial silk spinning techniques. In this study, we address this challenge by employing a graphene plasmonic infrared sensor in conjunction with multi-scale molecular dynamics (MD). This unique approach allows us to probe the secondary structure of nanoscale assembly intermediates (0.8–6.2 nm) and their morphological evolution. It also provides insights into the dynamics of silk fibroin (SF) over extended molecular timeframes. Our novel findings reveal that amorphous SFs undergo a conformational transition towards β-sheet-rich oligomers on graphene. These oligomers then connect to evolve into SNFs. These insights provide a comprehensive picture of SNF assembly, paving the way for advancements in biomimetic silk spinning.

Abstract Polaritons are well-established carriers of light, electrical signals, and even heat at the nanoscale in the setting of on-chip devices. However, the goal of achieving practical polaritonic manipulation over small distances deeply below the light diffraction limit remains elusive. Here, we implement nanoscale polaritonic in-plane steering and cloaking in a low-loss atomically layered van der Waals (vdW) insulator, α-MoO3, comprising building blocks of customizable stacked and assembled structures. Each block contributes specific characteristics that allow us to steer polaritons along the desired trajectories. Our results introduce a natural materials-based approach for the comprehensive manipulation of nanoscale optical fields, advancing research in the vdW polaritonics domain and on-chip nanophotonic circuits.

Abstract Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children’s brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3–10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.

Abstract Background The eastern edge of the Qinghai‒Tibet Plateau (QTP) and subtropical China have various regions where plant species originate and thrive, but these regions have been the focus of very few integrative studies. Here, we elucidated the phylogeographic structure of a continuous and widespread Akebia trifoliata population across these two regions. Results Sixty-one populations consisting of 391 genotypes were examined to assess population diversity and structure via network distribution analysis, maximum likelihood phylogenetic tree reconstruction, divergence time estimation, demographic history inference, and ancestral area reconstruction of both conserved internal transcribed spacer (ITS) and chloroplast (rps16) DNA sequences. The results showed that the ITS region was more variable than the rps16 region and could be suitable for studying intraspecific phylogeography. The A. trifoliata population displayed high genetic diversity, genetic differentiation and obvious phylogeographical structure, possibly originating on the eastern QTP, expanding during the last glacial-interglacial cycle, diverging in the early Pleistocene and middle Pleistocene, and extensively migrating thereafter. The migration route from west to east along rivers could be largely responsible for the long-distance dispersal of this species, while three main refuges (Qinba Mountains, Nanling Mountains and Yunnan-Guizhou Plateau) with multiple ice shelters facilitated its wide distribution. Conclusions Our results suggested that the from west to east long migration accompanying with the minor short reciprocal migration in the south-north direction, and the three main refuges (the Qinba Mountains, Nanling Mountains and Yunnan-Guizhou Plateau) contributed to the extant geographical distribution of A. trifoliata. In addition, this finding also strongly reduced the discrepancy between glacial contraction and postglacial expansion and the in situ survival hypothesis by simultaneously considering the existence of many similar climate-related ecological niches and migration influences.

Abstract Intelligent detection of athlete behavior is beneficial for guiding sports instruction. Existing mature target detection algorithms provide significant support for this task. However, large-scale target detection algorithms often encounter more challenges in practical application scenarios. We propose SCB-YOLOv5, to detect standardized movements of gymnasts. First, the movements of aerobics athletes were captured, labeled using the labelImg software, and utilized to establish the athlete normative behavior dataset, which was then enhanced by the dataset augmentation using Mosaic9. Then, we improved the YOLOv5 by (1) incorporating the structures of ShuffleNet V2 and convolutional block attention module to reconstruct the Backbone, effectively reducing the parameter size while maintaining network feature extraction capability; (2) adding a weighted bidirectional feature pyramid network into the multiscale feature fusion, to acquire precise channel and positional information through the global receptive field of feature maps. Finally, SCB-YOLOv5 was lighter by 56.9% than YOLOv5. The detection precision is 93.7%, with a recall of 99% and mAP value of 94.23%. This represents a 3.53% improvement compared to the original algorithm. Extensive experiments have verified that our method. SCB-YOLOv5 can meet the requirements for on-site athlete action detection. Our code and models are available at https://github.com/qingDu1/SCB-YOLOv5 .

Abstract Background Hemorrhagic fever with renal syndrome (HFRS) signals a recurring risk in Eurasia in recent years owing to its continued rise in case notifications and the extension of geographical distribution. This study was undertaken to investigate the spatiotemporal drivers and incidence heterogeneity of HFRS transmission in Shandong Province. Methods The epidemiological data for HFRS, meteorological data and socioeconomic data were obtained from China Information System for Disease Control and Prevention, China Meteorological Data Sharing Service System, and Shandong Statistical Yearbook, respectively. The spatial-temporal multicomponent model was employed to analyze the values of spatial-temporal components and the heterogeneity of HFRS transmission across distinct regions. Results The total effect values of the autoregressive, epidemic, and endemic components were 0.451, 0.187, and 0.033, respectively, exhibiting significant heterogeneity across various cities. This suggested a pivotal role of the autoregressive component in propelling HFRS transmission in Shandong Province. The epidemic component of Qingdao, Weifang, Yantai, Weihai, and Jining declined sharply at the onset of 2020. The random effect identified distinct incidence levels associated with Qingdao and Weifang, signifying regional variations in HFRS occurrence. Conclusions The autoregressive component emerged as a significant driver in the transmission of HFRS in Shandong Province. Targeted preventive measures should be strategically implemented across various regions, taking into account the predominant component influencing the epidemic.

Abstract With the continuous construction of urban traffic roads, more and more new roads are cut off by existing roads to form “dead end roads”. There is an urgent need for a trenchless method suitable for urban ultra-shallow overburden to build the undercrossing tunnel. To solve this problem, this paper proposed the micro pipe jacking and joint assembly structure (MPJ & JAS) method, which has the characteristics of shallow burial depth, low cost, short construction time, flexible cross-section setting and high space utilization. The MPJ & JAS method construct a large cross-section tunnel through assembling small cross-section elements, quite different from traditional methods. Therefore, this paper designed a CT-shaped integrated joint, the mechanical performance of which was verified and clarified by tensile test. The bending test and finite element (FE) analysis proved the reliability of MPJ & JAS tunnel structure, and confirmed the structure performances such as the failure models, crack behaviors, load–deflection response and stress–strain distribution. Moreover, the influences of the steel plate thickness, concrete strength and shear connector spacing were determined by the FE analysis. On the basis of test results and reasonable assumptions, a theoretical design method considering the influence of the CT-shaped integrated joint was proposed, which can effectively predict the bending strength of the MPJ & JAS tunnel structure with an error of less than 10%. Finally, in view of the characteristics of the MPJ & JAS method, the suitable micro pipe jacking machine, soil reinforcement measure, hydraulic traction construction technology, high-precision guidance system and concrete construction quality detection method based on the phased array ultrasonic imaging technology were developed, supporting the accurate and efficient construction of the MPJ & JAS tunnel.

Abstract Public concern regarding safety policies serious consequences is anticipated to persist over an extended duration. A study examining a case of rapid public health policy adaptation in China during the COVID-19 epidemic was conducted by gathering public opinion data from major social media platforms. A systematic approach to comprehend public opinion was developed. Five fundamental elements and four dimensions were delineated. An indicator system was established utilizing the K-means text clustering model. Public prediction, expectation, and their evolution underlying public concern were elucidated employing TF–IDF text mining models. The HMM elucidated the way public opinion influences policy adjustments. The findings underscore that public concern regarding enduring events undergoes temporal shifts, mirroring the evolution of public opinion towards policy. Public opinion aroused by both the original event and derived events collaboratively influence policy adjustments. In China, public opinion serves as a mechanism for policy feedback and oversight; notably, negative public sentiment plays a pivotal role in expediting policy transitions. These findings aid in refining policies to mitigate emergencies through a feedback loop, thereby averting the emergence of safety risks such as social unrest prompted by public opinion.

Objectives: To investigate the factors influencing imipenem/cilastatin (IMI) and meropenem (MEM) concentrations in critically ill adult patients and the role of these concentrations in the clinical outcome. Methods: Plasma trough concentrations of IMI and MEM were detected by high-performance liquid chromatography. A target value of 100%-time above MIC was used for the drugs. Results: A total of 186 patients were included, with 87 receiving IMI and 99 receiving MEM. The percentages of patients reaching the target IMI and MEM concentrations were 44.8% and 38.4%, respectively. The proportions of patients infected with drug-resistant bacteria were 57.5% and 69.7% in the IMI group and MEM group, respectively. In the multivariate analysis, the risk factors for an IMI concentration that did not reach the target were infection with drug-resistant bacteria, and those for MEM were infection with drug-resistant bacteria, estimated glomerular filtration rate, and diabetes mellitus. A total of 47.1% of patients had good outcomes in the IMI cohort, and 38.1% of patients had good outcomes in the MEM cohort. The duration of mechanical ventilation and IMI concentration were associated with ICU stay in patients in the IMI cohort, while MEM concentration and severe pneumonia affected the clinical outcome of patients in the MEM cohort. Conclusion: Infection with drug-resistant bacteria is an important factor influencing whether IMI and MEM concentrations reach the target. Furthermore, IMI and MEM concentrations are associated with the clinical outcome, and elevated doses of IMI and MEM should be given to patients who are infected with drug-resistant bacteria.

Object detection on drone-view images is vital for applications like intelligent transportation, abnormal behavior detection, and urban surveillance. However, the diverse perspectives and altitudes from which Unmanned Aerial Vehicle (UAV) capture scenes pose challenges due to multi-scale differences and small object sizes. To address this, we propose CSSDet, emphasizing multi-scale object detection and small object enhancement. CSSDet integrates an additional detection head for small objects and employs a bidirectional weighted feature pyramid network for effective cross-scale feature fusion, enhancing global perceptual capability. Additionally, we introduce coordinate attention and Involution modules to mitigate information loss. Experiments are conducted on two publicly available datasets, VisDrone and UAVDT. Quantitative results from the experiments indicate that the proposed CSSDet achieves optimal performance across a wide range of evaluation metrics, with particular strengths demonstrated in multi-scale object detection and small-size object detection. Qualitative results showcase its remarkable effectiveness in various aspects of object detection, including small object detection, objects at different scales and categories, multi-perspective scenarios, and complex scenes. The substantial experimental findings confirm that CSSDet attains comprehensive object detection performance on drone-view images. The source code is available at https://github.com/Gui-Cheng/CSSDet.

Conventional uniform lattice structures are subject to non-uniform loads or concentrated loads alternating back and forth during service, which can no longer meet the refinement requirements. In this paper, SiCp/SiC gradient lattice structures are prepared by selective laser sintering (SLS) technology and polymer impregnation pyrolysis (PIP) process, and compression standard specimens with different tilt angles are prepared according to the structural model by changing the printing direction, to analyze the influence of the anisotropic properties of the materials due to the SLS molding technology on the load-bearing behaviour of the core rod, and to further study the mechanical properties of the gradient lattice structures and the Failure behaviour. The results show that: with the increase of the angle of printing direction, the compression performance of the densification specimen decreases gradually; the compression strength of the gradient lattice structure is 13.95 MPa. During compression, the core rods with tilt angles of 60° and 75° mainly exhibit shear failure and crushing failure, respectively. The theoretical and simulated compression strengths were 16.08 and 16.32 MPa, respectively. This paper provides a new insight into the research and application of gradient lattice structures.

Introduction: Insomnia is a chronic disease affecting a third of the global adult population. Hehuan Anshen Decoction (HHASD), an innovative formula derived from Traditional Chinese medicine, has demonstrated therapeutic efficacy in treating insomnia, however, the potential pharmacological mechanism underlying its anti-insomnia effects remains incompletely elucidated. This study aimed to explore the underlying mechanism of HHASD treatment in mice with insomnia induced by p-Chlorophenylalanine (PCPA). Methods: The active constituents of HHASD were analysed by means of UPLCHRMS. PCPA mice were administered HHASD orally for 7 days. The anti-insomnia phenotype of HHASD were assessed by behavioral tests, encompassing the open field test and pentobarbital sodium-induced sleep test, alongside the measurement of hypothalamic 5-HT levels. Then, we conducted an in-depth analysis of specific ferroptosis markers, considering biochemistry, genetics and morphology. Additionally, ferroptosis inhibitor RSL3 was used to observe the underlying mechanism of the effects of HHASD. Results: HHASD could effectively improve the insomnia behaviors induced by PCPA, resulting in increased movement trajectories, decreased sleep latency and prolonged sleep duration. Specifically, HHASD exerted a neuroprotective effect by enhancing the integrity of Nissl bodies in the hypothalamus of the PCPA mice. Mechanistic analysis revealed that HHASD could reverse the hypothalamic ferroptosis phenotype of insomnia mice by restoring the lowered levels of glutathione (GSH), inhibiting iron accumulation and elevated malondialdehyde (MDA), and mitigating mitochondrial cristae damage. Furthermore, HHASD enhanced the expression of SLC7A11 and GPX4 and reduced the ASCL4 in the hypothalamus, while the anti-insomnia effect of HHASD in the PCPA mice was eliminated by the GPX4 inhibitor RLS3. Conclusion: HHASD ameliorates insomnia-related behaviors and protects against neuronal damage by suppressing ferroptosis by regulation GPX4 signaling. This study is not only a valuable attempt to explore the potential mechanism of Traditional Chinese formula but also will provide a novel targeted therapy for the treatment strategy of insomnia.

The rapid advancement in Earth observation technologies has improved the acquisition of precise data on terrestrial changes. However, traditional binary change detection (BCD) fails to satisfy the complex demands of contemporary applications. In contrast, semantic change detection (SCD) can identify changed areas and further detect the types of changes in ground objects. Nonetheless, current SCD approaches pose significant challenges, including the inadequate extraction and utilization of multi-level features and limited synergistic integration of related tasks. This paper proposes a multi-level feature-aggregated network (MLFA-Net), which decomposes the SCD task into two related subtasks: ground object classification and BCD of bi-temporal images. To optimize the classification performance, MLFA-Net incorporates feature alignment and cross-level feature aggregation modules that operate between the encoders and decoders, achieving effective extraction, aggregation, and utilization of multi-level image features. MLFA-Net also integrates symmetric transform feature aggregation modules between classification and BCD branches, leveraging prior knowledge to facilitate cross-task transmission of multi-level information and further optimize SCD results. MLFA-Net achieved [Formula: see text] of 0.6214 and 0.3581 on Landsat-SCD and SECOND datasets, respectively, with improvements of at least 0.0402 and 0.0035 compared to other methods. Quantitative and qualitative experiments validate the efficacy and superiority of the proposed MLFA-Net in SCD tasks.

Introduction It remains difficult for patients with spinal cord injury (SCI) to fully recover their sensory and motor functions; thus, they must rely on the assistance of caregivers to complete activities of daily living. This leads to psychological distress and decreased quality of life in patients and caregivers. Interventions for dyadic coping are a promising option. However, no studies have examined the effects of dyadic coping interventions on patients with SCI and their spouses. Therefore, our team constructed a dyadic coping intervention programme for couples with SCI.Method and analysis This two-arm, parallel-design, pilot randomised controlled trial will recruit 72 couples with SCI from two tertiary hospitals in Hefei, China. Couples will be randomly allocated to two arms. Couples randomly assigned to the intervention group will receive the usual care and the dyadic coping intervention. Couples randomly assigned to the control group will receive usual care only. The primary outcomes will be the feasibility and acceptability of the dyadic coping intervention for couples with SCI. Secondary outcomes will be quality of life, psychological distress, caregiver burden, marital satisfaction and dyadic coping. Outcomes will be collected at three time points: baseline (T0), post-intervention (T1) and after a follow-up period of 8 weeks (T2).Ethics and dissemination This study has been approved by the Research Ethics Committee of Anhui Medical University (84240008). The results will be published in a peer-reviewed journal.Trial registration number ChiCTR2300074556.

Background: The purpose of this study was to examine the feasibility and practical application of ultrasound (US) super-resolution imaging (SRI) in evaluating microvasculature and measuring renal allograft function. Methods: Sixteen consecutive patients who received kidney transplants were prospectively enrolled. The patients were assigned as: normal allograft function (n = 6), and allograft malfunction (n = 10). Localizing each potential contrast signal resulted in super-resolution images (SRI). SRI was utilized to assess micro-vessel density (MVD) and microvascular flow rate, whereas contrast-enhanced (CE) US images were statistically processed to get the time to peak (TTP) and peak intensity. Logistic regression was utilized to evaluate their relationship. Results: US SRI may be utilized effectively on allografts to show microvasculature with significantly higher resolution than typical color Doppler flow and CEUS pictures. In the multivariate analysis, MVD and TTP were significant US markers of renal allograft failure (p = 0.031 and p = 0.045). The combination of MVD and TTP produced an AUC of 0.783 (p

Existing remaining useful life (RUL) prediction methods considering multi-source variability were not applicable to the situation that the uneven measurement interval distribution and inconsistent measurement frequency of degrading equipment. This type of method also has ignored the variability of adaptive drift in the future degradation process. In view of this, based on adaptive Wiener process, the paper proposes a new nonlinear degradation method of the RUL prediction. Firstly, adopting the adaptive Wiener process, we have constructed the nonlinear degradation model with multi-source variability, which randomness of the parameters in the nonlinear function. Secondly, the real-time estimation of multiple hidden states can be realized by the particle filter algorithm. It has derived the RUL distribution in the sense of first hitting time. Using monitoring data of degrading equipment, the adaptive update of model parameters was implemented by expectation maximization algorithm. Finally, the effectiveness and superiority of the proposed model are validated through numerical simulation and lithium-ion battery experiments. The results show that it can effectively improve the prediction accuracy, which has potential application value.

Heavy metal-induced neuroinflammation is a significant pathophysiologic mechanism in Alzheimer's disease (AD). Microglia-mediated neuroinflammation plays a crucial role in the pathogenesis of AD. Multiple miRNAs are differentially expressed in peripheral tissues after heavy metal exposure, and increasing evidence suggests that they are involved in AD progression by regulating microglial homeostasis. Exosomes, which are capable of loading miRNAs and crossing the bloodbrain barrier, serve as mediators of communication between peripheral tissues and the brain. In this review, we summarize the current evidence on the link between miRNAs in peripheral tissues and neuroinflammation in AD after heavy metal exposure and propose a role for miRNAs in the microglial neurodegenerative phenotype (MGnD) of AD. This study will help to elucidate the link between peripheral tissue damage and MGnD-mediated neuroinflammation in AD after heavy metal exposure. Additionally, we summarize the regulatory effects of natural compounds on peripheral tissue-derived miRNAs, which could be potential therapeutic targets for natural compounds to regulate peripheral tissue-derived exosomal miRNAs to ameliorate heavy metal-induced MGnD-mediated neuroinflammation in patients with AD after heavy metal exposure.

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease triggered by a novel bunyavirus (SFTSV). Characterized by fever, thrombocytopenia, leukocytopenia, and multiple organ dysfunction manifestations, its primary mode of transmission is through tick bites. Despite the critical role of lipid metabolism in viral infections, the role of lipids in SFTS remains unclear.MethodsThis retrospective study analyzed 602 patients with SFTS treated at the Shandong Public Health Clinical Center from January 2021 to December 2023. Based on the endpoint events, patients were classified into survival (S) and death (D) groups. The S group was further classified into non-critical (non-C) and critical (C) groups based on symptoms. All patients were followed up for at least 28 days after admission. Propensity score matching, multivariable logistic regression, survival analysis, time trend analysis, and mediation analysis were conducted to assess the association between LDL-C levels and prognosis in SFTS.ResultsThe serum LDL-C levels on admission were significantly lower in the D and C groups than in the S and non-C groups. The logistic regression models indicated a potential association between LDL-C levels and a poor prognosis in SFTS. The restricted cubic spline showed a unidirectional trend between LDL-C levels and mortality, with a cutoff value of 1.59 mmol/L. The survival analysis revealed higher and earlier mortality in the low-LDL-C group than in the high-LDL-C group. The trends over 28 days post-admission showed that the serum LDL-C levels gradually increased in SFTS, with a favorable prognosis. Finally, the mediation analysis indicated that low LDL-C levels are associated with mortality through poor hepatic, cardiac, and coagulation functions.ConclusionLow LDL-C levels are potentially associated with a poor prognosis in SFTS.

The quaternion cubature Kalman filter (QCKF) algorithm has emerged as a prominent nonlinear filter algorithm and has found extensive applications in the field of GNSS/SINS integrated attitude determination and positioning system (GNSS/SINS-IADPS) data processing for unmanned aerial vehicles (UAV). However, on one hand, the QCKF algorithm is predicated on the assumption that the random model of filter algorithm, which follows a white Gaussian noise distribution. The noise in actual GNSS/SINS-IADPS is not the white Gaussian noise but rather a ubiquitous non-Gaussian noise. On the other hand, the use of quaternions as state variables is bound by normalization constraints. When applied directly in nonlinear non-Gaussian system without considering normalization constraints, the QCKF algorithm may result in a mismatch phenomenon in the filtering random model, potentially resulting in a decline in estimation accuracy. To address this issue, we propose a novel Gaussian sum quaternion constrained cubature Kalman filter (GSQCCKF) algorithm. This algorithm refines the random model of the QCKF by approximating non-Gaussian noise with a Gaussian mixture model. Meanwhile, to account for quaternion normalization in attitude determination, a two-step projection method is employed to constrain the quaternion, which consequently enhances the filtering estimation accuracy. Simulation and experimental analyses demonstrate that the proposed GSQCCKF algorithm significantly improves accuracy and adaptability in GNSS/SINS-IADPS data processing under non-Gaussian noise conditions for Unmanned Aerial Vehicles (UAVs).

Summary: In this protocol, we present a facile nanoscale thermal mapping technique for electronic devices by use of atomic force microscopy and a phase change material Ge2Sb2Te5. We describe steps for Ge2Sb2Te5 thin film coating, Ge2Sb2Te5 temperature calibration, thermal mapping by varying heater power, and thermal mapping by varying heating time. The protocol can be applied for resolving surface temperatures of various operational microelectronic devices with a nanoscale precision.For complete details on the use and execution of this protocol, please refer to Cheng et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.