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Anbang Zhao,1,2,* Bin Hao,1,2,* Simin Liu,3,* Xiaoyu Qiu,1,2,* Xiaoping Ming,1,2 Xiuping Yang,1,2 Jie Cai,1,2 Zhen Li,4,5 Xiong Chen1,2 1Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Sleep Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Neurosurgery, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 5Bariatric and Metabolic Disease Surgery Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiong Chen, Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China, Email zn_chenxiong@whu.edu.com Zhen Li, Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China, Email kamel_li@163.comPurpose: The diagnosis of severe OSA still relies on polysomnography, which causes a strong sense of restraint in patients with obesity. However, better prediction tools for severe OSA applicable to patients with obesity have not been developed.Patients and Methods: Relevant clinical data of 1008 patients with OSA who underwent bariatric surgery in our hospital were collected retrospectively. Patients were divided into training and test cohorts by machine learning. Univariate and multivariate logistic regression analysis was used to screen associations, including liver stiff measurement (LSM) and abdominal visceral tissue (aVAT), and to construct a severe OSA risk prediction nomogram. Then, we evaluated the effectiveness of our model and compared our model with the traditional Epworth Sleepiness Scale (ESS) model. Finally, our associations were used to explore the correlation with other indicators of OSA severity.Results: Our study revealed that age, biological sex, BMI, LSM, aVAT, and LDL were independent risk factors for severe OSA in patients with obesity. A severe OSA risk prediction nomogram constructed by six indicators possessed high AUC (0.845), accuracy (77.6%), and relatively balanced specificity and sensitivity (72.4%, 82.8%). The Hosmer-Lemeshow test (P=0.296, 0.785), calibration curves, and DCA of the training and test cohorts suggested better calibration and more net clinical benefit. Compared with the traditional ESS model, our model had higher AUC (0.829 vs 0.545), sensitivity (78.9% vs 12.2%), PPV (77.9% vs 53.3%), and accuracy (75.4% vs 55.2%). In addition, the associations in our model were independently correlated with other indicators reflecting OSA severity.Conclusion: We provided a simple, cheap, and non-invasive nomogram of severe OSA risk prediction for patients with obesity, which would be helpful for preventing further complications associated with severe OSA.Plain Language Summary: Question: Can we predict severe OSA in patients with obesity by their metabolic complications through some non-invasive examinations?Findings: Compared with traditional questionnaires, we developed and validated a new prediction model, including liver stiffness measurement and abdominal visceral adipose tissue, to screen severe OSA in bariatric surgery candidates through non-invasive examinations, which may contribute to perioperative safety and ultimate weight loss outcomes.Meaning: For patients with obesity who are in hospital because of metabolic disorders, it is necessary for them to be screened for possible severe OSA according to our new prediction nomogram, which is helpful for preventing further complications and perioperative risk associated with severe OSA.Keywords: obstructive sleep apnea, obesity, liver stiffness measurement, visceral adipose tissue, nomogram

Aiyun Yang,1 Tao Wen,2 Boya Hao,2 Yiling Meng,2 Xue Zhang,2 Tian Wang,2 Jie Meng,2 Jian Liu,2 Jianhua Wang,1 Haiyan Xu2 1Beijing Municipal Key Laboratory of Child Development and Nutriomics, Department of Translational Medicine, Capital Institute of Pediatrics, Beijing, People’s Republic of China; 2Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Haiyan Xu; Tao Wen, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, 5 Dong Dan San Tiao, Dongcheng District, Beijing, People’s Republic of China, Tel +86 106 915 6437, Email xuhy@pumc.edu.cn; went@ibms.pumc.edu.cnPurpose: Pt-based nanostructures are one of the promising nanomaterials for being used in catalysts, sensors, and therapeutics. However, their impacts on the health and biological systems are not adequately understood yet.Methods: In this work, nanorods composed of ultrasmall platinum (Pt) nanoparticles deposited on the surface and gold nanorod as the core (Au@Pt NRs) were synthesized, and the distribution and toxic effects of Au@Pt NRs were investigated in C57BL/6 mice with intravenous injection by using atomic absorption spectroscopy (AAS), transmission electron microscope (TEM), hematoxylin-eosin (HE) staining and blood cell analyzer.Results: At the time point of Day 1, Day 8 and Day 16 post injection of Au@Pt NRs (6 mg/kg of Pt atom), Au@Pt NRs were mainly accumulated in the liver and spleen. The energy dispersive spectrometer mapping images showed Au@Pt NRs experienced quick corrosion and Au released faster than Pt in the physiological environments. The catalase (CAT) activity in tissues increased slightly in the early stage of the Au@Pt NRs exposure and went down to the normal level. With HE staining, inflammatory cells infiltration could be seen in the tissues, while no significant influences were detected on the blood biochemistry and the function of liver and kidney.Conclusion: In conclusion, intravenously injected Au@Pt NRs mainly distributed in the liver and spleen with comparable levels, and did not exert any significant toxic effects on the organs’ function within two weeks; meanwhile, Au@Pt NRs were able to degrade, which indicated acceptable safety to the mice and potentials of biomedical application.Keywords: noble metal nanoparticles, distribution, toxicity, oxidative stress, intravenous injection

Song Gao,1,* Jianfeng Li,2 Chen Jiang,2 Bo Hong,3 Bing Hao4,* 1Department of Clinical Laboratory, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 2Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 3Department of Pathology, The Second Affiliated Hospital, 4Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: A gene drug delivery system for glioma therapy based on transferrin (Tf)-modified polyamidoamine dendrimer (PAMAM) was prepared. Gene drug, tumor necrosis factor-related apoptosis-inducing ligand (hTRAIL)-encoding plasmid open reading frame (pORF-hTRAIL, Trail), was condensed by Tf-modified PAMAM to form nanoparticles (NPs). PAMAM-PEG-Tf/DNA NPs showed higher cellular uptake, in vitro gene expression, and cytotoxicity than PAMAM-PEG/DNA NPs in C6 cells. The in vivo targeting efficacy of NPs was visualized by ex vivo fluorescence imaging. Tf-modified NPs showed obvious glioma-targeting trend. Plasmid encoding green fluorescence protein (GFP) was also condensed by modified or unmodified PAMAM to evaluate the in vivo gene expression level. The PAMAM-PEG-Tf/plasmid encoding enhanced green fluorescence protein (pEGFP) NPs exhibited higher GFP expression level than PAMAM-PEG/pEGFP NPs. TUNEL assay revealed that Tf-modified NPs could induce much more tumor apoptosis. The median survival time of PAMAM-PEG-Tf/Trail-treated rats (28.5 days) was longer than that of rats treated with PAMAM-PEG/Trail (25.5 days), temozolomide (24.5 days), PAMAM-PEG-Tf/pEGFP (19 days), or saline (17 days). The therapeutic effect was further confirmed by magnetic resonance imaging. This study demonstrated that targeting gene delivery system had potential application for the treatment of glioma. Keywords: gene therapy, BBB, hTRAIL, PAMAM, C6 glioma

Sustainable development in the building sector requires the integration of energy efficiency and renewable energy utilization in buildings. In recent years, the concept of net zero energy buildings (NZEBs) has become a potential plausible solution to improve efficiency and reduce energy consumption in buildings. To achieve an NZEB goal, building systems and design strategies must be integrated and optimized based on local climatic conditions. This paper provides a comprehensive review of NZEBs and their current development in hot and humid regions. Through investigating 34 NZEB cases around the world, this study summarized NZEB key design strategies, technology choices and energy performance. The study found that passive design and technologies such as daylighting and natural ventilation are often adopted for NZEBs in hot and humid climates, together with other energy efficient and renewable energy technologies. Most NZEB cases demonstrated site annual energy consumption intensity less than 100 kW-hours (kWh) per square meter of floor space, and some buildings even achieved “net-positive energy” (that is, they generate more energy locally than they consume). However, the analysis also shows that not all NZEBs are energy efficient buildings, and buildings with ample renewable energy adoption can still achieve NZEB status even with high energy use intensity. This paper provides in-depth case-study-driven analysis to evaluate NZEB energy performance and summarize best practices for high performance NZEBs. This review provides critical technical information as well as policy recommendations for net zero energy building development in hot and humid climates.

This study investigated the effect of a mixed obstacle layout on the deflagration mechanism of propane--air premixed gases. Most previous studies focused on a single type of obstacle, changing the shape and number of the obstacles to observe the effect on the flame deflagration characteristics. However, in real explosion accident sites, obstacles are often a mixture of different types. Little literature exists on the deflagration characteristics of hybrid barriers in semiconfined spaces. In this paper, the deflagration characteristics of propane-air premixed gas with a mixed structure of hurdles and square obstacles was studied. First, the effectiveness of numerical simulations was demonstrated by comparing experimental and large eddy simulation (LES) results for the flame dynamics with a single flat plate obstacle. Based on this, the flame behavior for different layouts of square obstacles in a mixed obstacle configuration was further simulated using the large eddy simulation method, focusing on the flame behavior, overpressure characteristics, and flow field structure in the vicinity of the obstacle. The results showed that a mixed obstacle promoted flame evolution more than a single obstacle when the square obstacle was within a critical distance from the ignition source location at the same moment in time. When the flame front crossed the first hurdle-type obstacle, the flame pattern spread in a "cat's paw" pattern to the unburned portion of the tube. In addition, the increased distance of the square obstacle from the ignition source did not allow the peak overpressure and the peak rate of overpressure rise to show a positive feedback mechanism. Finally, the strength of the vorticity in the flow field was positively correlated with the distance of the square obstacle from the ignition source. The results of study provide theoretical for the prevention of explosions. [ABSTRACT FROM AUTHOR]

Upper mantle deformation is mainly controlled by the mechanical behavior of olivine. Crystallographic preferred orientations (CPOs) develop in olivine due to crystal‐plastic deformation during mantle flow, where the a‐axes of olivine polycrystalline aggregates are aligned with the flow direction. Therefore, the observed CPO in olivine‐rich rocks is used as an indicator of the mantle flow direction. Experimental data show that olivine rheology is strongly controlled by the microstructure. While the influence of plastic deformation is in general well characterized, the role of dynamic recrystallization during deformation is not totally understood, limiting our ability to interpret the deformation history of naturally deformed rocks. This contribution presents microdynamic numerical simulations of olivine polycrystalline aggregates with different iron content (i.e., fayalite content) with the aim of exploring the CPO and grain size response to dynamic recrystallization. We use a full‐field approach with an explicit simulation of viscoplastic deformation and dynamic recrystallization processes under simple shear boundary conditions up to high strain. The simulations show that the CPOs are similar and practically reach the same maximum regardless of the iron content. CPOs are characterized by a single cluster of a‐axis and two‐clusters of b‐axis, reveling a joint activity of the easy glide [100](010) and the moderate strength [100](010) slip systems. High‐strain domains of our models are consistent with experimental results, showing an A‐type fabric with double maxima, and where the CPO is aligned with the shear direction. The model provides a deeper understanding of the dynamic recrystallization influence on olivine CPOs resulting from plastic deformation. Plain Language Summary: Rocks in the upper mantle of the Earth are mainly composed of olivine. This mineral has a significant impact on how the upper mantle behaves mechanically. When the mantle flows, olivine undergoes viscoplastic deformation, leading to the formation of crystallographic preferred orientations (CPO). By studying the observed crystallographic preferred orientations in olivine‐rich rocks, scientists can determine the direction of mantle flow. However, how dynamic recrystallization affects the CPO is not well understood. This study conducts microdynamic numerical simulations of olivine aggregates to investigate the impact on the microstructure and CPO under dynamic recrystallization during viscoplastic deformation. The modeling approach is the cutting‐edge viscoplastic fast Fourier transform in conjunction with the ELLE modeling platform. The high‐strain regions in our models align with the experimental findings, revealing a double‐maxima A‐type fabric and where the CPO is oriented with the shear direction. This model enhances our comprehension of how dynamic recrystallization influences the deformation of olivine rocks. Key Points: We present the first full‐field numerical model incorporating dynamic recrystallization applied to olivine microstructuresHigh‐strain domains of our models are consistent with experimental results, showing an A‐type fabric with double maxima, and where the CPO is aligned with the shear directionMicrostructures formed by pure fayalite show higher grain boundary mobility than those composed of forsterite and fayalite [ABSTRACT FROM AUTHOR]

Disrupted in schizophrenia 1 (DISC1) is a multi-functional scaffolding protein that has been associated with neuropsychiatric disease. The role of DISC1 is to assemble protein complexes that promote neural development and signaling, hence tight control of the concentration of cellular DISC1 in neurons is vital to brain function. Using structural and biochemical techniques, we show for we believe the first time that not only is DISC1 turnover elicited by the ubiquitin proteasome system (UPS) but that it is orchestrated by the F-Box protein, FBXW7. We present the structure of FBXW7 bound to the DISC1 phosphodegron motif and exploit this information to prove that disruption of the FBXW7-DISC1 complex results in a stabilization of DISC1. This action can counteract DISC1 deficiencies observed in neural progenitor cells derived from induced pluripotent stem cells from schizophrenia patients with a DISC1 frameshift mutation. Thus manipulation of DISC1 levels via the UPS may provide a novel method to explore DISC1 function.

The bullet shape is critical in efficient bullet design because it affects the lift and drag forces. This paper proposes a new bullet shape with a logarithmic curve and analyzes the lift and drag coefficients of bullets with different curves under different angles of attack. The results are compared with a bullet whose shape is described by the power law curve. Fluent simulations demonstrate that the optimal power exponent values are 0.65, 0.6, and 0.65 for the bullet with the power law curve and 1.3, 1, and 1 for the bullet with the logarithmic curve at 0°, 30°, and 40° angles of attack, respectively. At a 0° angle of attack, the lift coefficient of the logarithmic curve is the largest. The lift force of the bullet with the logarithmic curve is 129.4% higher than that with the von Karman curve. The drag coefficient is the largest for the bullet with the rectilinear curve; it is 1.30% larger than that of the bullet with the logarithmic curve. At 30° and 40° angles of attack, the lift coefficient of the bullet with the power law curve is larger. The difference in the lift coefficients between the two angles of attack is 18.47%. The bullet's drag coefficient is the largest for the logarithmic curve, and the difference in the drag coefficients between the two angles of attack is 18.59%. [ABSTRACT FROM AUTHOR]

Researchers recently synthesized a new orthorhombic allotrope of silicon, namely Cmcm Si24. This work studied the effect of one vacancy for Cmcm Si24 on structural, electronic, and mechanical anisotropy properties by the first principle calculation. The lattice parameters of Cmcm Si24:V are the same as Cmcm Si24, but the density of Cmcm Si24:V is larger than that of Cmcm Si24. Moreover, the values of elastic moduli for Cmcm Si24:V are smaller than for Cmcm Si24. The Cmcm Si24:V has mechanical stability and anisotropy and has lower formation energy than diamond-Si. The analysis of the band structures shows that Cmcm Si24 is an indirect band gap material, and the value of the band gap is 1.08 eV. In particular, electronic band structures of Cmcm Si24:V exhibit metallic characteristics. Furthermore, the electron localization function indicated strong covalent silicon--silicon bonds in Cmcm Si24 and Cmcm Si24:V. In addition, the effective mass of electrons and holes of Cmcm Si24 is smaller than that of diamond-Si along the a direction, and larger than that along the b and c directions. Finally, the X-ray diffraction patterns for Cmcm Si24 and Cmcm Si24:V are very close after 13:84°. [ABSTRACT FROM AUTHOR]

In the field of hydrogen safety and combustion, the effect of obstacles on hydrogen deflagration is a topic of general interest to scholars. In previous studies, scholars usually used uniform obstacles under various operating conditions and obtained conclusions by changing their number and positions. However, in practice, the shapes of obstacles at an accident site are often not the same and regular. In this paper, a series of obstacles with variations in length were investigated, and the effects of the obstacles on hydrogen deflagration under different working conditions were analyzed. The configuration of the obstacles with gradually increasing lengths amplified the vortices in the flow field so that the propagation direction of the flame front surface was reversed after passing three obstacles. The variations in the lengths of the obstacles had a significant stretching effect on the propagation of the flame and a considerable acceleration effect on the propagation speed of the flame. The main reason for the acceleration was the rapid propagation of the flame achieved by the vortex when rupture occurred. The change in the pressure gradient that occurred at the center of rotation caused rapid movement of the combustion gases, which ultimately led to an increase in the flame propagation speed. A configuration with gradually increasing lengths of the obstacles promoted the overpressure. A configuration with gradually decreasing lengths of the obstacles suppressed the overpressure. The reason for the formation of the local high-pressure area was that unburned gas was accumulated there by pressure waves and the obstacle walls, and then the thermal expansion formed a high pressure. The Rayleigh-Taylor and Kelvin-Helmholtz instabilities caused the overpressure to rise further. The results can provide a theoretical basis for hydrogen transportation, storage, and safety. [ABSTRACT FROM AUTHOR]

The formation of supercavitation after a high-speed projectile enters water has a decisive impact on the underwater ballistic and penetration of the projectile. In this study, Ansysfluent19.0 simulation software is used to study water entry of a chosen projectile at velocities of 300, 400, 500, and 600 m/s. The underwater cavitation characteristics, trajectories, and flow-field characteristics are analyzed for a 5.8-mm caliber conical flat head projectile, as well as for t wo other projectiles of the same caliber and different head shapes -- conical cone head and elliptical flat head -- entering water vertically at the same velocities. The attenuation rate of water entry velocity increases with the increase of velocity. Within first 3ms, the velocity attenuation rate of the conical flat-head projectile with a water entry velocity of 600m / s is 55.6 %, while the velocity attenuation rate of the projectile with a water entry velocity of 300m / s is only 16.3 % within 3ms. Among the head shapes considered, the conical flat head projectile is the most stable for vertical water entry. The stability of an elliptical flat head projectile is worse, and the trajectory stability of a conical cone head projectile is still worse. [ABSTRACT FROM AUTHOR]

Abstract With the development of sustainable economy, new energy materials are widely used in various industries, and many cars also adopt new energy power batteries as power sources. However, it is currently not possible to accurately diagnose faults in power batteries, which results in the safety of power batteries not being guaranteed. To address this issue, this study utilizes the Whale Optimization Algorithm to improve the Long Short-Term Memory algorithm and constructs a fault diagnosis model based on the improved algorithm. The purpose of using this model for fault diagnosis of power batteries is to strengthen the safety management of batteries. This study first conducted experiments on the improved algorithm and obtained an accuracy of 95.3%. The simulation results of the fault diagnosis model showed that the diagnosis time was only 1.2s. The analysis of the power battery showed that after using this model, the safety performance has been improved by 90.1%, while the maintenance cost has been reduced to 20.3% of the original. The above results verify that the fault diagnosis model based on the improved algorithm can accurately diagnose faults in power batteries, thereby improving the safety of power batteries.

[Objective] This study aimed to improve the quality of Yanbian yellow beef during storage. [Methods] Yanbian yellow cattle eye meat and buttocks were used as experimental materials. Low frequency and high intensity (power 360 W, frequency 40 kHz) ultrasound technology was used to treat beef, and the effects of different ultrasound treatment time (0, 40, 60, 80 min) on the physical and chemical properties of beef during 10 days of storage were investigated. [Results] Extending ultrasonication treatment time significantly decreased the shear stress and redness value of beef (P＜0.05). Moreover, the analysis of myofibrils in beef after ultrasonic treatment showed that the microfibril fragmentation index increased significantly with the extension of ultrasonic time (P＜0.05). [Conclusion] Ultrasonic treatment for 80 min resulted in the lowest shear stress, the highest MFI and the best tenderness.

Addressing peripheral nerve defects remains a significant challenge in regenerative neurobiology. Autografts emerged as the gold-standard management, however, are hindered by limited availability and potential neuroma formation. Numerous recent studies report the potential of wireless electronic system for nerve defects repair. Unfortunately, few has met clinical needs for inadequate electrode precision, poor nerve entrapment and insufficient bioactivity of the matrix material. Herein, we present an advanced wireless electrical nerve stimulator, based on water-responsive self-curling silk membrane with excellent bioabsorbable and biocompatible properties. We constructed a unique bilayer structure with an oriented pre-stretched inner layer and a general silk membrane as outer layer. After wetting, the simultaneous contraction of inner layer and expansion of outer layer achieved controllable super-contraction from 2D flat surface to 3D structural reconfiguration. It enables shape-adaptive wrapping to cover around nerves, overcomes the technical obstacle of preparing electrodes on the inner wall of the conduit, and prevents electrode breakage caused by material expansion in water. The use of fork capacitor-like metal interface increases the contact points between the metal and the regenerating nerve, solving the challenge of inefficient and rough electrical stimulation methods in the past. Newly developed electronic stimulator is effective in restoring 10 mm rat sciatic nerve defects comparable to autologous grafts. The underlying mechanism involves that electric stimulation enhances anterograde mitochondrial transport to match energy demands. This newly introduced device thereby demonstrated the potential as a viable and efficacious alternative to autografts for enhancing peripheral nerve repair and functional recovery.

Abstract Renewable-driven electrocatalytic nitrate conversion offers a promising alternative to alleviate nitrate pollution and simultaneously harvest green ammonia. However, due to the complex proton-electron transfer processes, the reaction mechanism remains elusive, thereby limiting energy efficiency. Here, we adopt Ni(OH)₂ as a model catalyst to investigate the dynamic evolution of the reaction interface. A proposed OH cycle mechanism involves the formation of a locally OH-enriched microenvironment to promote the hydrogenation process, which is identified through in-situ spectroscopy and isotopic labelling. By further activating the dynamic state through the implementation of surface vacancies via plasma, we achieve a high Faradaic efficiency of almost 100%. The activated interface accelerates the OH cycle by enhancing dehydroxylation, water dissociation, and OH adsorption, thereby promoting nitrate electroreduction and inhibiting hydrogen evolution. We anticipate that rational activation of the dynamic interfacial state can facilitate electrocatalytic interface activity and improve reaction efficiency.

Abstract Magnons, bosonic quasiparticles carrying angular momentum, can flow through insulators for information transmission with minimal power dissipation. However, it remains challenging to develop a magnon-based logic due to the lack of efficient electrical manipulation of magnon transport. Here we show the electric excitation and control of multiferroic magnon modes in a spin-source/multiferroic/ferromagnet structure. We demonstrate that the ferroelectric polarization can electrically modulate the magnon-mediated spin-orbit torque by controlling the non-collinear antiferromagnetic structure in multiferroic bismuth ferrite thin films with coupled antiferromagnetic and ferroelectric orders. In this multiferroic magnon torque device, magnon information is encoded to ferromagnetic bits by the magnon-mediated spin torque. By manipulating the two coupled non-volatile state variables—ferroelectric polarization and magnetization—we further present reconfigurable logic operations in a single device. Our findings highlight the potential of multiferroics for controlling magnon information transport and offer a pathway towards room-temperature voltage-controlled, low-power, scalable magnonics for in-memory computing.

Abstract Magnetic skyrmions are topological spin textures that are regarded as promising information carriers for next-generation spintronic memory and computing devices. For practical applications, their deterministic generation, manipulation, and efficient detection are the most critical aspects. Although the generation and manipulation of skyrmions have been extensively studied, efficient electrical detection of mobile skyrmions by using techniques that are compatible with modern magnetic memory technology, remains to be adequately addressed. Here, through integrating magnetic multilayers that host nanoscale skyrmions, together with the magnetic tunnel junctions (MTJ), we demonstrate the electrical detection of skyrmions by using the tunneling magnetoresistance (TMR) effect with a TMR ratio that reaches over 100% at room temperature. By building prototype three-terminal racetrack-like devices, we further show the electrical detection of mobile skyrmions by recording the time-dependent TMR ratios. Along with many recent developments, our results could advance the development of skyrmionic memory and logic devices.

Abstract Background Resistance to immune checkpoint inhibitors (ICIs) represents a major unmet medical need in non-small cell lung cancer (NSCLC) patients. Vascular endothelial growth factor (VEGF) inhibition may reverse a suppressive microenvironment and recover sensitivity to subsequent ICIs. Methods This phase Ib/IIa, single-arm study, comprised dose-finding (Part A) and expansion (Part B) cohorts. Patients with ICIs-refractory NSCLC were enrolled to receive anlotinib (a multi-target tyrosine kinase inhibitor) orally (from days 1 to 14 in a 21-day cycle) and nivolumab (360 mg every 3 weeks, intravenously) on a 21-day treatment cycle. The first 21-day treatment cycle was a safety observation period (phase Ib) followed by a phase II expansion cohort. The primary objectives were recommended phase 2 dose (RP2D, part A), safety (part B), and objective response rate (ORR, part B), respectively. Results Between November 2020 and March 2022, 34 patients were screened, and 21 eligible patients were enrolled (6 patients in Part A). The RP2D of anlotinib is 12 mg/day orally (14 days on and 7 days off) and nivolumab (360 mg every 3 weeks). Adverse events (AEs) of any cause and treatment-related AEs (TRAEs) were reported in all treated patients. Two patients (9.5%) experienced grade 3 TRAE. No grade 4 or higher AEs were observed. Serious AEs were reported in 4 patients. Six patients experienced anlotinib interruption and 4 patients experienced nivolumab interruption due to TRAEs. ORR and disease control rate (DCR) was 19.0% and 76.2%, respectively. Median PFS and OS were 7.4 months (95% CI, 4.3-NE) and 15.2 months (95% CI, 12.1-NE), respectively. Conclusion Our study suggests that anlotinib combined with nivolumab shows manageable safety and promising efficacy signals. Further studies are warranted. Trial registration NCT04507906 August 11, 2020.

Abstract Background Early detection of colorectal neoplasms can reduce the colorectal cancer (CRC) burden by timely intervention for high-risk individuals. However, effective risk prediction models are lacking for personalized CRC early screening in East Asian (EAS) population. We aimed to develop, validate, and optimize a comprehensive risk prediction model across all stages of the dynamic adenoma-carcinoma sequence in EAS population. Methods To develop precision risk-stratification and intervention strategies, we developed three trans-ancestry PRSs targeting colorectal neoplasms: (1) using 148 previously identified CRC risk loci (PRS148); (2) SNPs selection from large-scale meta-analysis data by clumping and thresholding (PRS183); (3) PRS-CSx, a Bayesian approach for genome-wide risk prediction (PRSGenomewide). Then, the performance of each PRS was assessed and validated in two independent cross-sectional screening sets, including 4600 patients with advanced colorectal neoplasm, 4495 patients with non-advanced adenoma, and 21,199 normal individuals from the ZJCRC (Zhejiang colorectal cancer set; EAS) and PLCO (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; European, EUR) studies. The optimal PRS was further incorporated with lifestyle factors to stratify individual risk and ultimately tested in the PLCO and UK Biobank prospective cohorts, totaling 350,013 participants. Results Three trans-ancestry PRSs achieved moderately improved predictive performance in EAS compared to EUR populations. Remarkably, the PRSs effectively facilitated a thorough risk assessment across all stages of the dynamic adenoma-carcinoma sequence. Among these models, PRS183 demonstrated the optimal discriminatory ability in both EAS and EUR validation datasets, particularly for individuals at risk of colorectal neoplasms. Using two large-scale and independent prospective cohorts, we further confirmed a significant dose–response effect of PRS183 on incident colorectal neoplasms. Incorporating PRS183 with lifestyle factors into a comprehensive strategy improves risk stratification and discriminatory accuracy compared to using PRS or lifestyle factors separately. This comprehensive risk-stratified model shows potential in addressing missed diagnoses in screening tests (best NPV = 0.93), while moderately reducing unnecessary screening (best PPV = 0.32). Conclusions Our comprehensive risk-stratified model in population-based CRC screening trials represents a promising advancement in personalized risk assessment, facilitating tailored CRC screening in the EAS population. This approach enhances the transferability of PRSs across ancestries and thereby helps address health disparity. Graphical Abstract

Abstract Purpose To evaluate the intracavity left ventricular (LV) blood flow kinetic energy (KE) parameters using four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) in patients with acute myocardial infarction (AMI). Methods Thirty AMI patients and twenty controls were examined via CMR, which included cine imaging, late gadolinium enhancement (LGE) and global heart 4D flow imaging. The KE parameters were indexed to LV end-diastolic volume (EDV) to obtain average, systolic and diastolic KE as well as the proportion of LV in-plane KE (%). These parameters were compared between the AMI patients and controls and between the two subgroups. Results Analysis of the LV blood flow KE parameters at different levels of the LV cavity and in different segments of the same level showed that the basal level had the highest blood flow KE while the apical level had the lowest in the control group. There were no significant differences in diastolic KE, systolic in-plane KE and diastolic in-plane KE between the anterior wall and posterior wall (p > 0.05), only the systolic KE had a significant difference between them (p

Geological disasters in the Emei to Mianning section of the Chengdu–Kunming Railway located in southwestern China occur frequently, and many debris flow gullies are distributed along the line. Debris flows often cause damage to the railway and highway that threatens the safe operation of the original line and the double-track line. Along the railway, the debris flow outbreak risks are analyzed for 53 debris flow gullies using field survey, remote sensing interpretation, and numerical simulation. Their developmental characteristics were judged according to the code. The results are used for numerical simulation of debris flow to further determine the movement characteristics and the accumulation range of debris flow. The results are combined with high-definition satellite images to analyze the form of the railway passing from the mouth of the ditch and the simulation results to determine the impact on the safe operation of the Chengdu–Kunming Railway when the debris flow erupts. Finally, disaster prevention and mitigation projects are proposed, and the prevention and control effects of the proposed works are validated.

ABSTRACT: The wide distribution and diverse varieties of chickens make them important models for studying genetic adaptation. The aim of this study was to identify genes that alter heat adaptation in commercial chicken breeds by comparing genetic differences between tropical and cold-resistant chickens. We analyzed whole-genome resequencing data of 186 chickens across various regions in Asia, including the following breeds: Bian chickens (B), Dagu chickens (DG), Beijing-You chickens (BY), and Gallus gallus jabouillei from China; Gallus gallus murghi from India; Vietnam native chickens (VN); Thailand native chickens (TN) and Gallus gallus spadiceus from Thailand; and Indonesia native chickens (IN), Gallus gallus gallus, and Gallus gallus bankiva from Indonesia. In total, 5,454,765 SNPs were identified for further analyses. Population genetic structure analysis revealed that each local chicken breed had undergone independent evolution. Additionally, when K = 5, B, BY, and DG chickens shared a common ancestor and exhibited high levels of inbreeding, suggesting that northern cold-resistant chickens are likely the result of artificial selection. In contrast, the runs of homozygosity (ROH) and the ROH-based genomic inbreeding coefficient (FROH) results for IN, TN, and VN chickens showed low levels of inbreeding. Low population differentiation index values indicated low differentiation levels, suggesting low genetic diversity in tropical chickens, implying increased vulnerability to environmental changes, decreased adaptability, and disease resistance. Whole-genome selection sweep analysis revealed 69 candidate genes, including LGR4, G6PC, and NBR1, between tropical and cold-resistant chickens. The genes were further subjected to GO and KEGG enrichment analyses, revealing that most of the genes were primarily enriched in biological synthesis processes, metabolic processes, central nervous system development, ion transmembrane transport, and the Wnt signaling pathway. Our study identified heat adaptation genes and their functions in chickens that primarily affect chickens in high-temperature environments through metabolic pathways. These heat-resistance genes provide a theoretical basis for improving the heat-adaptation capacity of commercial chicken breeds.