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Abstract Imaging antiferromagnetic 180° domains with actively controlled visibility is vital for both fundamental science and sophisticated applications. While optical second-harmonic generation (SHG) is a well-known technique for distinguishing such domains in non-centrosymmetric antiferromagnets, a general material-based strategy to control domain contrast remains elusive. Using van der Waals antiferromagnet MnPS3 as a proof of concept, we demonstrate the tuning of nonreciprocity-induced domain contrast in SHG through applying an in-plane electric field that transforms the magnetic point group to its unitary subgroup. The interference among intrinsic electric-dipole, magnetic-dipole, and field-induced electric-dipole transitions, each carrying distinct characters under space-inversion ( $${{\mathcal{P}}}$$ P ) and time-reversal ( $${{\mathcal{T}}}$$ T ) operations, enables large tuning of domain contrast and nonreciprocity in a broad spectral range. This strategy, generically applicable to systems characterized by $${{\mathcal{P}}}{{\mathcal{T}}}$$ P T -symmetric magnetic groups with a polar unitary subgroup, offers a path to fast electrical modulation of nonlinear nonreciprocal photonic behaviors using antiferromagnets.

In recent years, bridge safety accidents caused by insufficient shear bearing capacity of bridges have attracted increasing attention. The main causes include internal factors such as insufficient bridge section and deterioration of steel bars, as well as external factors, for example, vehicle load surge and improper maintenance. To address this issue to some degree, this article adopts the method of strengthening RC beams with ultra-high performance concrete (UHPC) and conducts parameter analysis using finite element method, taking into consideration the influence of four parameters: reinforcement material, reinforcement thickness, reinforcement length, and reinforcement form on the shear strengthening characteristics of RC rectangular beams. After obtaining the optimal reinforcement plan through parameter analysis, the author applied the research results to an existing bridge with insufficient shear strength. It then turned out that the shear bearing capacity of the reinforced bridge’s inclined section increased by approximately 27.1%. Simple and fast in construction, this reinforcement method is one of the methods that is effective to increase cross-section reinforcement; besides, it features good economic characteristics and applicability.

Summary: Background: Microplastics are environmental pollutants detected in various human organs and tissues. These particles originate from multiple sources including the degradation of larger plastic items and the intentional inclusion in consumer goods. Potential risks for human health resulting from microplastics exposure have also been reported. However, the distribution in the male reproductive system and its effect remains largely unknown. This study aims to investigate the presence of multiple microplastics in human semen and urine and their association with sperm quality in a multi-site study across China. Methods: We conducted a cross-sectional study involving 113 male participants from three regions in China. Semen and urine samples were collected and analysed using Raman microscopy to detect eight types of microplastics: polystyrene (PS), polypropylene (PP), polycarbonate (PC), polyethylene (PE), polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE), polyethylene terephthalate (PET), and acrylonitrile butadiene styrene (ABS). Semen quality parameters, including total sperm count, concentration, motility, and morphology, were assessed. Statistical analyses, including single and multi-variable models, were used to evaluate the relationship between microplastic exposure and semen quality, with a focus on PTFE, after adjusting confounding factors of age, body mass index (BMI), smoking, alcohol drinking, and sites. Findings: Microplastics were detected in all semen and urine samples, with participants typically exposed to 3–5 different types. The detection rates of PS, PP and PE were the highest. Notably, PTFE exposure was significantly associated with decreased semen quality. Participants exposed to PTFE showed reductions in total sperm count [188.90 ± 163.71 vs. 207.67 ± 132.36 million, p = 0.091], sperm concentration [52.13 ± 47.47 vs. 58.32 ± 37.26 million/mL, p = 0.041], and progressive motility [40.29% ± 19.06 vs. 34.11% ± 17.02, p = 0.083]. The multi-linear regression analysis indicated that each additional type of microplastic exposure was associated with a significant decrease in total sperm number [β = −15.4 (95% CI: −25.6, −5.2)], sperm concentration [β = −7.2 (95% CI: −12.4, −2.0)], and progressive motility [β = −8.3 (95% CI: −13.5, −3.1)]. Latent category analysis further refined these groups by types of microplastic exposure, highlighting specific types more strongly associated with decreased semen quality (OR = 3.5, 95% CI: 1.8, 6.9, p

Objective Patients with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular and cerebrovascular events (CCEs). Furthermore, CCE was a significant factor contributing to mortality in patients with SLE. However, no clinical model exists that can predict which patients are at high risk. The purpose of this study was to develop a practical model for predicting the risk of CCE in people with SLE.Methods This study was based on the Chinese SLE Treatment and Research Group cohort. A total of 2399 patients, who had a follow-up period of over 3 years and were diagnosed with SLE for less than 1 year at the start of the study, were included. Cox proportional hazards regression and least absolute shrinkage and selection operator regression were used to establish the model. Internal validation was performed, and the predictive power of the model was evaluated.Results During the follow-up period, 93 patients had CCEs. The prediction model included nine variables: male gender, smoking, hypertension, age of SLE onset >40, cutaneous involvement, arthritis, anti-β2GP1 antibody positivity, high-dose glucocorticoids and hydroxychloroquine usage. The model’s C index was 0.801. Patients with a prognostic index over 0.544 were classified into the high-risk group.Conclusion We have developed a predictive model that uses clinical indicators to assess the probability of CCE in patients diagnosed with SLE. This model has the ability to precisely predict the risk of CCE in patients with SLE. We recommended using this model in the routine assessment of patients with SLE.

Abstract The South Asian summer monsoon (SASM) is a significant monsoon system that exerts a profound impact on climate and human livelihoods. According to 38 models from the Coupled Model Intercomparison Project Phase 6, the SASM circulation is projected to weaken significantly under global warming as seen in the weakened low-level westerly wind over the northern tropical Indian Ocean; however, the associated climate dynamics is still under debate. Here, we identify that the weakened low-level westerly wind is closely related to the enhanced latent heating over the Tibetan Plateau (TP), which corresponds with increased summer precipitation in the future. The intensified TP latent heating triggers an anomalous meridional circulation with ascending motions over the plateau and descending motions to the south, leading to an anomalous low-level anticyclone over the northern tropical Indian Ocean. This anticyclone greatly weakens the prevailing low-level westerlies of the SASM through easterly anomalies at the anticyclone’s southern flank. Moisture budget analysis further reveals that increased atmospheric water vapor, rather than the vertical dynamic component, makes the largest contribution to the increased precipitation over the TP. This result confirms that the enhanced TP latent heating is a driver of atmospheric circulation change and contributes to weakening the SASM circulation.

Abstract An obvious long‐term drying trend in recent early springs (February–March–April) is observed over southeastern China (SEC). Here, we attribute this drying to the weakened subtropical westerlies and deflected by the Tibetan Plateau (TP). Climatologically, the low‐level southwesterlies at the southeastern margin of the TP, a branch of the upstream subtropical westerly jet deflected by the TP terrain, bring water vapor to SEC and the southerlies move upward over SEC mainly through isentropic gliding mechanism, inducing persistent precipitation in early spring. However, the subtropical westerlies weakened significantly in recent decades due potentially to the decreased Eurasian snow cover. Consequently, an easterly trend appears along the southern margin of the TP with anomalous northeasterlies over SEC. These northeasterlies suppress both moisture supply and upward motions over SEC, and reduce regional early spring precipitation. Our results highlight the interaction between the TP terrain and the weakened subtropical westerlies that leads to the drying SEC.

Abstract Corneal neovascularization (CNV) is a common clinical finding seen in a range of eye diseases. Current therapeutic approaches to treat corneal angiogenesis, in which vascular endothelial growth factor (VEGF) A plays a central role, can cause a variety of adverse side effects. The technology of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 can edit VEGFA gene to suppress its expression. CRISPR offers a novel opportunity to treat CNV. This study shows that depletion of VEGFA with a novel CRISPR/Cas9 system inhibits proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Importantly, subconjunctival injection of this dual AAV‐SpCas9/sgRNA‐VEGFA system is demonstrated which blocks suture‐induced expression of VEGFA, CD31, and α‐smooth muscle actin as well as corneal neovascularization in mice. This study has established a strong foundation for the treatment of corneal neovascularization via a gene editing approach for the first time.

Abstract Introduction Estrogen receptor (ER) positive patients compromise about 70% of breast cancers. Tamoxifen, an antagonist of ERα66 (the classic ER), is the most effective and the standard first-line drug. However, its efficacy is limited by the development of acquired resistance. Methods A specific inhibitor of Hsp70-Bim protein–protein interaction (PPI), S1g-2, together with an inhibitor of Hsp70-Bag3 PPI, MKT-077 and an ATP-competitive inhibitor VER155008, were used as chemical tools. Cell viability assays, co-immunoprecipitation and gene knockdown were used to investigate the role of Hsp70 in tamoxifen resistance. A xenograft model was established in which tamoxifen-resistant breast cancer (MCF-7/TAM-R) cells maintained in the presence of 5 μM tamoxifen were subcutaneously inoculated. The anti-tumor efficiency of S1g-2 was measured after a daily injection of 0.8 mg/kg for 14 days. Results It was revealed that Hsp70-Bim PPI protects ERα-positive breast cancer from tamoxifen-induced apoptosis through binding and stabilizing ERα36, rather than ERα66, resulting in sustained EGFR mRNA and protein expression. Disruption of Hsp70-Bim PPI and downregulation of ERα36 expression in tumor samples are consistent with the in vitro functions of S1g-2, resulting in about a three-fold reduction in tumor volume. Conclusions The in vivo activity and safety of S1g-2 illustrated that it is a potential strategy for Hsp70-Bim disruption to overcome tamoxifen-resistant ER-positive breast cancer.

Abstract This study investigates the impact of urbanization on extreme winter rainfall in the South China Greater Bay Area (GBA) through the analysis of hourly station observations and simulations using the Weather Research and Forecasting Model with the Single Layer Urban Canopy Model (WRF-SLUCM). Data from 2008 to 2017 reveal that urban areas in the GBA experience lower 99th percentile hourly winter rainfall intensity compared to surrounding rural regions. However, urban locations exhibit higher annual maximum hourly rainfall (Rmax) and very extreme rainfall events (99.99th percentile) in winter, suggesting a positive influence of urbanization on extreme winter precipitation. A case study further underscores the role of the Urban Heat Island (UHI) effect in enhancing extreme rainfall intensity and probability in the GBA urban areas. Additionally, two extreme cases were dynamically downscaled using WRF-SLUCM, involving four parallel experiments: replacing urban land use with cropland (Nourban), using historical urban land use data from 1999 (99LS), projecting near-future urban land use for 2030 (30LS), and considering 2030 urban land use without anthropogenic heat (AH) (30LS-AH0). Synoptic analysis demonstrates that cold air intrusion suppresses the GBA UHI in Case 2013 but not in Case 2015. Reduced evaporation and humidity induced by urban surfaces significantly decrease urban precipitation in Case 2013. In contrast, the persistent UHI in Case 2015 enhances local convection and land–ocean circulation, leading to increased moisture flux convergence and amplified urban precipitation intensity and probability in 30LS compared to Nourban. This amplification is primarily attributed to AH, while the change in 99LS remains insignificant. These findings suggest that urban influences on extreme precipitation in the GBA persist during winter, particularly when the UHI effect is maintained.

Abstract The anomalous Hall effect (AHE) that emerges in antiferromagnetic metals shows intriguing physics and offers numerous potential applications. Magnets with a rutile crystal structure have recently received attention as a possible platform for a collinear-antiferromagnetism-induced AHE. RuO2 is a prototypical candidate material, however the AHE is prohibited at zero field by symmetry because of the high-symmetry [001] direction of the Néel vector at the ground state. Here, we show AHE at zero field in Cr-doped rutile, Ru0.8Cr0.2O2. The magnetization, transport and density functional theory calculations indicate that appropriate doping of Cr at Ru sites reconstructs the collinear antiferromagnetism in RuO2, resulting in a rotation of the Néel vector from [001] to [110] while maintaining a collinear antiferromagnetic state. The AHE with vanishing net moment in the Ru0.8Cr0.2O2 exhibits an orientation dependence consistent with the [110]-oriented Hall vector. These results demonstrate that material engineering by doping is a useful approach to manipulate AHE in antiferromagnetic metals.

Electricity demand forecasting is of great significance to the electricity system and residents’ life, but it is difficult to forecast the electricity demand series because of the influence of cyclical factors. Electricity demand forecasting also faces the problem of small data amounts. Therefore, we need to design a model that is less affected by data volume and can cope with complex electricity demand series. Based on the Autoformer model, this paper establishes a novel forecasting framework with excellent performance. In the part of data preprocessing, multiple linear regression with 10 variables and Bootstrap processing are added. In the part of the model, the Auto-Correlation mechanism is modified to better extract the historical and nonlinear characteristics of electricity demand series from different time spans. Using this framework, we further analyze the impact of working days and seasonal changes on the electricity demand in Taixing City and New South Wales. In addition, we propose a new electricity demand forecasting method, which can adjust the original sequence according to the actual situation. The experimental results show that this method can achieve good precision in demand forecasting. Taking Taixing of China and New South Wales of Australia as examples, the forecasting performance with the proposed framework is better than that of Autoformer, Reformer, Informer, and other mainstream models. The forecasting indexes with our proposed framework of the test set are MAE: 35.05, RMSE: 47.28, MAPE: 1.63 in Taixing and MAE: 193.17, RMSE: 239.96, MAPE: 2.43 in NSW.

Heavy metal pollution is one of the most devastating abiotic factors, significantly damaging crops and human health. One of the serious problems it causes is a rise in cadmium (Cd) toxicity. Cd is a highly toxic metal with a negative biological role, and it enters plants via the soil–plant system. Cd stress induces a series of disorders in plants’ morphological, physiological, and biochemical processes and initiates the inhibition of seed germination, ultimately resulting in reduced growth. Fiber crops such as kenaf, jute, hemp, cotton, and flax have high industrial importance and often face the issue of Cd toxicity. Various techniques have been introduced to counter the rising threats of Cd toxicity, including reducing Cd content in the soil, mitigating the effects of Cd stress, and genetic improvements in plant tolerance against this stress. For decades, plant breeders have been trying to develop Cd-tolerant fiber crops through the identification and transformation of novel genes. Still, the complex mechanism of Cd tolerance has hindered the progress of genetic breeding. These crops are ideal candidates for the phytoremediation of heavy metals in contaminated soils. Hence, increased Cd uptake, accumulation, and translocation in below-ground parts (roots) and above-ground parts (shoots, leaves, and stems) can help clean agricultural lands for safe use for food crops. Earlier studies indicated that reducing Cd uptake, detoxification, reducing the effects of Cd stress, and developing plant tolerance to these stresses through the identification of novel genes are fruitful approaches. This review aims to highlight the role of some conventional and molecular techniques in reducing the threats of Cd stress in some key fiber crops. Molecular techniques mainly involve QTL mapping and GWAS. However, more focus has been given to the use of transcriptome and TFs analysis to explore the potential genomic regions involved in Cd tolerance in these crops. This review will serve as a source of valuable genetic information on key fiber crops, allowing for further in-depth analyses of Cd tolerance to identify the critical genes for molecular breeding, like genetic engineering and CRISPR/Cas9.

The knapsack problem is a typical bi-objective combinatorial optimization issue, wherein maximizing the value of the packed items is achieved concurrently with minimizing the weight of the load. Due to the conflicting objectives of the knapsack problem and the typical discrete property of the items involved, swarm intelligence algorithms are commonly employed. The diversity of optimal combinations in the knapsack problem has become a focal point, which involves finding multiple packing solutions at the same value and weight. For this purpose, this paper proposes a Multi-Objective Equilibrium Optimizer Algorithm based on Weighted Congestion Distance (MOEO_WCD). The algorithm employs a non-dominated sorting method to find a set of Pareto front solutions rather than a single optimal solution, offering multiple decision-making options based on the varying needs of the decision-makers. Additionally, MOEO_WCD improves the balance pool generation mechanism and incorporates a weighted congestion incentive, emphasizing the diversity of packing combination solutions under the objectives of value and weight to explore more Pareto front solutions. Considering the discrete characteristics of the knapsack combination optimization problem, our algorithm also incorporates appropriate discrete constraint handling. This paper designs multiple sets of multi-objective knapsack combinatorial optimization problems based on the number of knapsacks, the number of items, and the weights and values of the items. This article compares five algorithms suitable for solving multi-objective problems: MODE, MO-PSO-MM, MO-Ring-PSO-SCD, NSGA-II, and DN-NSGAII. In order to evaluate the performance of the algorithm, this paper proposes a new solution set coverage index for evaluation. We also used the hypervolume indicator to evaluate the diversity of algorithms. The results show that our MOEO-WCD algorithm achieves optimal coverage of the reference composite Pareto front in the decision space of four knapsack problems. The experimental results indicate that our MOEO_WCD algorithm achieves the optimal coverage of the reference composite Pareto front in the decision space for four sets of knapsack problems. Although our MOEO_WCD algorithm covers less of the composite front in the objective space compared with the MODE algorithm for knapsack problem 1, its coverage of the integrated reference solutions in the decision space is greater than that of the MODE algorithm. The experiments demonstrate the superior performance of the MOEO_WCD algorithm on bi-objective knapsack combinatorial optimization problem instances, which provides an important solution to the search for diversity in multi-objective combinatorial optimization solutions.

Abstract Background Colorectal cancer (CRC) is one of the most common tumors in the world. Cholesterol plays an important role in the pathogenesis of tumors. One of the cholesterol transporters, scavenger receptor class B type 1 (SR‐B1), a multi‐ligand membrane receptor protein, is expressed in the intestines which also highly expressed in various tumors. But the potential mechanism of SR‐B1 in CRC development has not been reported. Aims This study aimed to clarify the importance of SR‐B1 in the development and prognosis of CRC as much as possible to provide a possible strategy in CRC treatment. Materials & Methods In this study, we used SR‐B1 gene knockdown mice to study the effect of SR‐B1 on colitis‐induced or APCmin/+‐induced CRC. The expression of related molecules were detected through the immunohistochemistry and hematoxylin–eosin staining, western blot analysis, and Flow cytometry. The gene expression and microbiota in microenvironment of CRC mice were analyzed through eukaryotic mRNA sequencing and 16S rRNA high‐throughput sequencing. Results The results showed that SR‐B1 knockdown reduced the tumor load of colitis‐induced or APCmin/+‐induced CRC. SR‐B1 knockdown improved the immune microenvironment by affecting the level of tumor‐associated macrophage (TAM), mononuclear myeloid‐derived suppressor cells (M‐MDSCs), granulocytic myeloid‐derived suppressor cells (G‐MDSCs), programmed cell death‐ligand 1 (PD‐L1), and human leukocyte antigen class I‐B (HLA‐B), and also reduced the level of low‐density lipoprotein receptor (LDL‐R), and increased the level of ATP binding cassette transporter A1 (ABCA1) to regulate the cholesterol metabolism, and regulated the expression of related genes and intestinal microbiota. SR‐B1 knockdown can also trigger the anti‐CRC effect of anti‐PD 1 in colitis‐induced CRC. Discussion SR‐B1 deficiency significantly improved the immunity in tumor microenvironment of colitis‐induced or APCmin/+‐induced CRC. In addition, the microbiota changes caused by SR‐B1 deficiency favor improving the immune response to chemotherapeutic drugs and anti‐PD1 therapy. The mechanism of action of SR‐B1 deficiency on the development of CRC still needs further in‐depth research. Conclusion This study provides a new treatment strategy for treating CRC by affecting the expression of SR‐B1 in intestine.

Abstract Following the 1923 Kanto earthquake in Japan, Japanese researchers noticed the strong effects of surface geology on seismic motion (ESG) and began to investigate these effects to quantify the site amplification factors (SAFs) associated with soft surface sediments. On the other side of the Pacific Ocean, ESG received limited attention until the 1985 Michoacan, Mexico earthquake revealed significant long-period amplification inside Mexico City that manifested as the source of devastating damage to high-rise buildings. Since then, seismologists and earthquake engineers have performed a lot of studies on various ESG issues worldwide. We have not yet reached common conclusions on how to quantitatively predict SAFs over a broad frequency band of engineering interest, 0.1 to 20 Hz, for moderate to strong input from different types of earthquakes in different tectonic settings. However, we found here several basic guidelines useful for successfully modeling ground motions as a common approach to ESG studies. First, in this letter, we briefly review our history of understanding ESG, which is closely related to the key settings required for reliable quantifications of SAFs, and then introduce various emerging techniques for broadband quantitative evaluations of SAFs based on the vast amount of observed ground motions primarily from dense Japanese strong-motion networks. Based on the findings of our investigation and the physical relationships behind the parameters, the authors would like to recommend that researchers on ESG and related topics would refer to the five basic guidelines proposed in the conclusions for the successful implementation of techniques to delineate SAFs in a specific region of interest, such as the use of Fourier spectra instead of response spectra. We have started applying the proposed techniques to regions outside Japan. The implementation of the statistical validation exercises will follow. Graphical Abstract

Abstract Background For cancer therapy, the identification of both selective autophagy targets and small molecules that specifically regulate autophagy is greatly needed. Heat shock protein 70 (Hsp70) is a recently discovered BH3 receptor that forms a protein‒protein interaction (PPI) with Bcl-2-interacting mediator of cell death (Bim). Herein, a specific inhibitor of the Hsp70-Bim PPI, S1g-2, and its analog S1, which is a Bcl-2-Bim disruptor, were used as chemical tools to explore the role of Hsp70-Bim PPI in regulating mitophagy. Methods Co-immunoprecipitation and immunofluorescence assays were used to determine protein interactions and colocalization patterns. Organelle purification and immunodetection of LC3-II/LC3-I on mitochondria, endoplasmic reticulum (ER) and Golgi were applied to identify specific types of autophagy. Cell-based and in vitro ubiquitination studies were used to study the role of the Hsp70-Bim PPI in parkin-mediated ubiquitination of outer mitochondrial membrane 20 (TOMM20). Results We found that after the establishment of their PPI, Hsp70 and Bim form a complex with parkin and TOMM20, which in turn facilitates parkin translocation to mitochondria, TOMM20 ubiquitination and mitophagic flux independent of Bax/Bak. Moreover, S1g-2 selectively inhibits stress-induced mitophagy without interfering with basal autophagy. Conclusions The findings highlight the dual protective function of the Hsp70-Bim PPI in regulating both mitophagy and apoptosis. S1g-2 is thus a newly discovered antitumor drug candidate that drives both mitophagy and cell death via apoptosis. Graphical Abstract

The demand for precise positioning in noisy environments has propelled the development of research on array antenna radar systems. Although the orthogonal matching pursuit (OMP) algorithm demonstrates superior performance in signal reconstruction, its application efficacy in noisy settings faces challenges. Consequently, this paper introduces an innovative OMP algorithm, DTM_OMP_ICA (a dual-threshold mask OMP algorithm based on independent component analysis), which optimizes the OMP signal reconstruction framework by utilizing two different observation bases in conjunction with independent component analysis (ICA). By implementing a mean mask strategy, it effectively denoises signals received by array antennas in noisy environments. Simulation results reveal that compared to traditional OMP algorithms, the DTM_OMP_ICA algorithm shows significant advantages in noise suppression capability and algorithm stability. Under optimal conditions, this algorithm achieves a noise suppression rate of up to 96.8%, with its stability also reaching as high as 99%. Furthermore, DTM_OMP_ICA surpasses traditional denoising algorithms in practical denoising applications, proving its effectiveness in reconstructing array antenna signals in noisy settings. This presents an efficient method for accurately reconstructing array antenna signals against a noisy backdrop.

Exciton-magnon pairwise excitation is promising to realize the direct and efficient photogeneration of magnons, especially in low-dimensional materials with large quasiparticle scattering cross sections. Using resonant second-harmonic generation spectroscopy, we identified exciton-magnon resonance in MnPS_{3} with possible splitting, in line with the exciton-induced modification of the magnon density of states based on our Koster-Slater-type theory. The substantial exciton-magnon interaction, favored by symmetry, sheds light on coherent cross control among charge, spin, and orbital degrees of freedom via quasiparticle correlations. Additionally, a large linear magnetoelectric effect of excitons is observed.

Abstract. Background:. The onset and clinical presentation of systemic lupus erythematosus (SLE) are sex-related. Few studies have investigated the distinctions in clinical characteristics and treatment preferences in male and female SLE patients in the initial cohort. This study aimed to improve the understanding of Chinese SLE patients by characterizing the different sexes of SLE patients in the inception cohort. Methods:. Based on the initial patient cohort established by the Chinese SLE Treatment and Research Group, a total of 8713 patients (795 men and 7918 women) with newly diagnosed SLE were enrolled between April 2009 and March 2021. Of these, 2900 patients (347 men and 2553 women) were eligible for lupus nephritis (LN). A cross-sectional analysis of the baseline demographic characteristics, clinical manifestations, laboratory parameters, organ damage, initial treatment regimens, and renal pathology classification was performed according to sex. Results:. In the SLE group, as compared to female patients, male patients had a later age of onset (male vs. female: 37.0 ± 15.8 years vs. 35.1 ± 13.7 years, P = 0.006) and a higher SLE International Collaborative Clinic/American College of Rheumatology damage index score (male vs. female: 0.47 ± 1.13 vs. 0.34 ± 0.81, P = 0.015), LN (male vs. female: 43.6% vs. 32.2%, P

Introduction: Proteins located in subcellular compartments have played an indispensable role in the physiological function of eukaryotic organisms. The pattern of protein subcellular localization is conducive to understanding the mechanism and function of proteins, contributing to investigating pathological changes of cells, and providing technical support for targeted drug research on human diseases. Automated systems based on featurization or representation learning and classifier design have attracted interest in predicting the subcellular location of proteins due to a considerable rise in proteins. However, large-scale, fine-grained protein microscopic images are prone to trapping and losing feature information in the general deep learning models, and the shallow features derived from statistical methods have weak supervision abilities.Methods: In this work, a novel model called HAR_Locator was developed to predict the subcellular location of proteins by concatenating multi-view abstract features and shallow features, whose advanced advantages are summarized in the following three protocols. Firstly, to get discriminative abstract feature information on protein subcellular location, an abstract feature extractor called HARnet based on Hybrid Attention modules and Residual units was proposed to relieve gradient dispersion and focus on protein-target regions. Secondly, it not only improves the supervision ability of image information but also enhances the generalization ability of the HAR_Locator through concatenating abstract features and shallow features. Finally, a multi-category multi-classifier decision system based on an Artificial Neural Network (ANN) was introduced to obtain the final output results of samples by fitting the most representative result from five subset predictors.Results: To evaluate the model, a collection of 6,778 immunohistochemistry (IHC) images from the Human Protein Atlas (HPA) database was used to present experimental results, and the accuracy, precision, and recall evaluation indicators were significantly increased to 84.73%, 84.77%, and 84.70%, respectively, compared with baseline predictors.

This study introduces an ensemble prediction methodology employing multiple machine learning algorithms for forecasting the frequency of typhoons (TYFs) over the western North Pacific (WNP) during June‒November. Potential predictors were initially identified based on the relationships between the year-by-year variation (DY) of the TYFs and preseason (March–May) environmental factors. These predictors were subsequently further refined, resulting in the selection of eight key predictors. Prediction models were constructed using twenty machine learning algorithms, utilizing data from 1965 to 2010. These trained models were then applied to perform hindcasts of TYFs from 2011 to 2023. The forecasted DY was added to the observed TYF of the preceding year to obtain the current year’s TYF. The results indicate that the TYFs predicted by the multi-model ensemble (MME) closely align with the observation during the hindcast period. Compared to individual models, the MME improves the prediction skill for the DY by at least 5.56% and up to 56.92%. Furthermore, the mean bias of the MME for TYF is notably smaller than that of the ECMWF’s most recent seasonal forecasting system (SEAS5) in the years of 2017‒2023. The superior performance of the ensemble prediction approach was also validated through leave-one-out cross-validation. This research underscores the potential of ensemble prediction approach utilizing multiple machine learning algorithms to improve the forecasting skill of TYF over the WNP.

The Location-Routing Problem (LRP) becomes a more intricate subject when the limits of capacities of vehicles and warehouses are considered, which is an NP-hard problem. Moreover, as the number of vehicles increases, the solution to LRP is exacerbated because of the complexity of transportation and the combination of routes. To solve the problem, this paper proposed a Discrete Assembly Combination-Delivery (DACA) strategy based on, the Binary Equilibrium Optimizer (BiEO) algorithm, in addition, this paper also proposes a mixed-integer linear programming model for the problem of this paper. Our primary objective is to address both the route optimization problem and the assembly group sum problem concurrently. Our BiEO algorithm was designed as discrete in decision space to meet the requirements of the LRP represented by the DACA strategy catering to the multi-vehicle LRP scenario. The efficacy of the BiEO algorithm with the DACA strategy is demonstrated. through empirical analysis utilizing authentic data from Changchun City, China, Remarkably, the experiments reveal that the BiEO algorithm outperforms conventional methods, specifically GA, PSO, and DE algorithms, resulting in reduced costs. Notably, the results show the DACA strategy enables the simultaneous optimization of the LRP and the vehicle routing problem (VRP), ultimately leading to cost reduction. This innovative algorithm proficiently tackles both the assembly group sum and route optimization problems intrinsic to multi-level LRP instances.

Abstract Sea surface temperature anomalies (SSTAs) over the North Atlantic could stimulate the El Niño–Southern Oscillation (ENSO) events through regulating the tropical and mid‐latitude atmospheric circulations. Whether the Tibetan Plateau (TP) play an important bridging role in the mid‐latitude pathway has been rarely considered. Observational analysis and model simulations show that the spring TP surface wind speed dipole mode forced by the winter–spring North Atlantic tripole SSTAs can induce surface zonal wind anomalies over the equatorial western Pacific from April to June through the Indo‐Pacific gearing process, favoring the occurrence of subsequent autumn–winter ENSO events through the Bjerknes feedback. Moreover, a flattened TP will obviously weaken the atmospheric and oceanic responses associated with ENSO development to the North Atlantic tripole SSTAs forcing. Quantitatively, the TP's bridging effect accounts for about 38% proportion in the above process. Our finding provides a new insight in understanding the mid‐latitude pathway.

Tumors and their location distinctly alter both local and global brain connectivity within the ipsilesional hemisphere of glioma patients.

Protein is one of the primary biochemical macromolecular regulators in the compartmental cellular structure, and the subcellular locations of proteins can therefore provide information on the function of subcellular structures and physiological environments. Recently, data-driven systems have been developed to predict the subcellular location of proteins based on protein sequence, immunohistochemistry (IHC) images, or immunofluorescence (IF) images. However, the research on the fusion of multiple protein signals has received little attention. In this study, we developed a dual-signal computational protocol by incorporating IHC images into protein sequences to learn protein subcellular localization. Three major steps can be summarized as follows in this protocol: first, a benchmark database that includes 281 proteins sorted out from 4722 proteins of the Human Protein Atlas (HPA) and Swiss-Prot database, which is involved in the endoplasmic reticulum (ER), Golgi apparatus, cytosol, and nucleoplasm; second, discriminative feature operators were first employed to quantitate protein image-sequence samples that include IHC images and protein sequence; finally, the feature subspace of different protein signals is absorbed to construct multiple sub-classifiers via dimensionality reduction and binary relevance (BR), and multiple confidence derived from multiple sub-classifiers is adopted to decide subcellular location by the centralized voting mechanism at the decision layer. The experimental results indicated that the dual-signal model embedded IHC images and protein sequences outperformed the single-signal models with accuracy, precision, and recall of 75.41%, 80.38%, and 74.38%, respectively. It is enlightening for further research on protein subcellular location prediction under multi-signal fusion of protein.

Abstract Atmospheric heat source/sink (AHS) of the Tibetan Plateau (TP) is strongly linked to the local snow depth. Based on the numerical simulations with Weather Research and Forecasting (WRF) model, connections between snow depth and the AHS across the TP in melting season (May–August) are investigated. Compared with the derived AHS from reanalysis data, spatial patterns and monthly evolution of the AHS are reasonably reproduced by the WRF model. The AHS can be significantly reduced (~80 W m−2) by snow over both the western and southeastern TP in early May, which is mainly ascribed to the weakened surface sensible heat (SH) and atmospheric latent heat. Obvious cooling effect of snow on the AHS is still found over the western TP even in mid‐summer. However, the cooling strength in late summer has declined to one‐fifth that of May and it is totally dominated by the reduced surface SH. As to the southeastern TP, snow is thin and scattered since June, resulting that the AHS response to snow depth declines significantly and even vanishes in mid‐summer. It is further clarified that there is no elevation‐dependent relationship between the AHS and snow over the TP, while the cooling amplitudes of the AHS varied with altitude are mainly determined by the corresponding snow depth.

Ultrasound is widely used in medical and engineering inspections due to its non-destructive and easy-to-use characteristics. However, the complex internal structure of plant stems presents challenges for ultrasound testing. The density and thickness differences in various types of stems can cause different attenuation of ultrasonic signal propagation and the formation of different echo locations. To detect structural changes in plant stems, it is crucial to acquire complete ultrasonic echo RF signals. However, there is currently no dedicated ultrasonic RF detection equipment for plant stems, and some ultrasonic acquisition equipment has limited memory capacity that cannot store a complete echo signal. To address this problem, this paper proposes a double-layer multiple-timing trigger method, which can store multiple trigger sampling memories to meet the sampling needs of different plant stems with different ultrasonic echo locations. The method was tested in experiments and found to be effective in acquiring complete ultrasonic RF echo signals for plant stems. This approach has practical significance for the ultrasonic detection of plant stems.

BackgroundThe efficacy and safety of antithrombotic treatment with oral anticoagulants (OACs) in elderly patients with comorbidities of acute coronary syndrome (ACS) and atrial fibrillation (AF) are unclear.MethodsA cohort of hospitalized elderly patients (≥65 years of age) diagnosed with ACS and AF and treated with oral antithrombotic agents were consecutively recruited. Follow-up was performed for at least 1 year. Major adverse cardiac events (MACEs) were defined as a composite of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, and systemic embolism. The safety outcomes of bleeding were defined according to the Bleeding Academic Research Consortium (BARC) criteria.ResultsA cohort of 548 eligible patients (76 ± 6.6 years) was analyzed. Compared to the patients with OAC treatment (n = 184, 33.6%), patients treated without OAC (n = 364, 66.4%) were older, had a lower prevalence of persistent AF and unstable angina (UA), and more often presented with paroxysmal AF, acute myocardial infarction (AMI), stent implantation and dual antiplatelet therapy (DAPT). Compared to the patients without OAC treatment (n = 364, 66.4%), patients treated with OAC (n = 184, 33.6%) had a lower risk of MACEs at both the 1-year (4.3 vs. 15.1%, adjusted HR: 0.34, 95% CI: 0.15–0.80, p = 0.014) and 5-year (17.5 vs. 48.4%, adjusted HR: 0.36, 95% CI: 0.19–0.67, p = 0.001) follow-up. No significant difference was observed for bleeding events of BARC ≥2 between the groups (8.0 vs. 9.0%, adjusted HR: 1.17, 95% CI: 0.58–2.34, p = 0.667). Compared with warfarin-treated patients, the non-vitamin K antagonist oral anticoagulant-treated patients had lower risks of all-cause mortality (2.1 vs. 9.5%, HR: 0.18, 95% CI: 0.03–0.98, p = 0.047) and bleeding events of BARC ≥ 3 (2.1 vs. 4.8%, HR: 0.14, 95% CI: 0.02–1.10, p = 0.062).ConclusionsAntithrombotic therapy with OACs in elderly patients with ACS and AF was associated with a lower risk of ischemic events without an increase in bleeding events. In real-world practice, the clinical awareness of anticoagulation treatments in elderly patients with ACS and AF needs to be strengthened.

When the initial size of an atom cloud in a cold atom interferometer is negligible compared to its size after free expansion, the interferometer is approximated to a point-source interferometer and is sensitive to rotational movements by introducing an additional phase shear in the interference sequence. This sensitivity on rotation enables a vertical atom-fountain interferometer to measure angular velocity in addition to gravitational acceleration, which it is conventionally used to measure. The accuracy and precision of the angular velocity measurement depends on proper extraction of frequency and phase from spatial interference patterns detected via the imaging of the atom cloud, which is usually affected by various systematic biases and noise. To improve the measurement, a pre-fitting process based on principal component analysis is applied to the recorded raw images. The contrast of interference patterns are enhanced by 7–12 dB when the processing is present, which leads to an enhancement in the precision of angular velocity measurements from 6.3 μrad/s to 3.3 μrad/s. This technique is applicable in various instruments that involve precise extraction of frequency and phase from a spatial interference pattern.

PurposeTo compare the predicted ablation depth (AD) with the postoperatively measured corneal ablation depth (postop-AD) at central, paracentral, and midperipheral locations using two rotating Scheimpflug analyzers and a Fourier-domain optical coherence tomographer in eyes that underwent femtosecond laser-assisted LASIK (FS-LASIK).MethodsThe values of corneal thickness were measured preoperatively and postoperatively at one and three months. The difference between preoperative and postoperative was defined as postop-AD. Measurements were performed at the corneal vertex and mid-peripheral area. The mid-peripheral corneal thickness was measured at the superior, inferior, nasal, and temporal locations at a distance of 1.0 or 2.5 mm from the corneal vertex. The predicted AD was calculated by ORK-CAM software (Schwind eye tech-solutions GmbH, Kleinostheim, Germany), and the difference between the predicted AD and postop-AD was defined as Δ-AD. Paired t-test analysis was employed to evaluate the differences, agreement was assessed by the Bland-Altman method.ResultsForty-two eyes of 42 patients were investigated. At one month, the predicted AD in the central and paracentral areas was underestimated by the Pentacam HR (Oculus, Wetzlar, Germany), Sirius (Costruzione Strumenti Oftalmici, Florence, Italy) and RTVue OCT (Optovue Inc., Freemont, CA, United States), whereas Δ-AD was negative as established by all devices and predominantly statistically significant. The Δ-AD values approximated zero at three months. The mean difference of Δ-AD at three months at the corneal vertex was 0.67 ± 9.39 mm, −7.92 ± 9.05 mm and −1.36 ± 8.31 mm, respectively. The mid-peripheral measurements had positive values at one month and even more highly positive at three months (with statistically significant differences in most of the cases). The agreement between the predicted and postop-AD was moderate with all devices, but slightly better with RTVue.ConclusionThe predicted AD seems to be underestimated in the central and paracentral corneal area and overestimated in the mid-periphery.Translational RelevanceThe study could help to partly explain and prevent the refractive errors after FS-LASIK.

Purpose: We aimed to describe the clinical characteristics and outcomes of patients with transverse myelitis (TM) as a rare manifestation in systemic lupus erythematosus (SLE) and explore the risk factors and prognosis of SLE-related TM (SLE-TM). Methods: We conducted a retrospective case–control and cohort analysis. All patients with SLE-TM (58 patients) and 232 with SLE without TM, as a control group, were admitted to Peking Union Medical College Hospital between January 1993 and May 2021. Factors associated with the presence of SLE-TM and its prognosis were assessed using logistic regression and Cox proportional hazard models. Results: Multivariate analysis revealed that positive anti-Ro/Sjogren’s syndrome A (anti-Ro/ SSA) (

Material interfaces are highly crucial to improve device performances. Here, the authors report interfacial reconstruction at the Au {001} substrate surface and the top MoS2 and WS2 monolayers due to the formation of a metastable interfacial Au4S4 phase. The reconstructed interface results in a p-type Schottky contact with reduced barrier height.

Gravitational search algorithm (GSA) inspired from physics emulates gravitational forces to guide particles' search. It has been successfully applied to diverse optimization problems. However, its search performance is limited by its inherent mechanism where gravitational constant plays an important role in gravitational forces among particles. To improve it, this paper uses chaotic neural oscillators to adjust its gravitational constant, named GSA-CNO. Chaotic neural oscillators can generate various chaotic states according to their parameter settings. Thus, we select four kinds of chaotic neural oscillators to form distinctive chaotic characteristics. Experimental results show that chaotic neural oscillators effectively tune the gravitational constant such that GSA-CNO has good performance and stability against four GSA variants on functions. Three real-world optimization problems demonstrate the promising practicality of GSA-CNO.

2D transition metal dichalcogenides (TMDs) are characterized by the presence of multiple crystal structures or phases, even at the ultrathin limit. Controlling phase transformations, namely, phase engineering, of 2D TMDs is crucial for realizing high‐performance 2D devices by combining phases with distinct physical and chemical properties. As a powerful approach for large‐scale production of high‐quality 2D TMDs, chemical vapor deposition (CVD) offers unique advantages in phase engineering due to its highly controllable synthesis processes. Starting with an introduction of the crystal structures and phase transformations of 2D TMDs, this review summarizes the recent developments in CVD‐mediated phase engineering strategies of TMDs, including control of temperature, precursors, catalysis, atmosphere, composition, and strain during the deposition process. Moreover, the representative applications of CVD‐based phase‐engineered TMDs in the field of transistors, photodetectors, photovoltaic cells, and catalysis are overviewed. Finally, the challenges, expectations of CVD‐based phase engineering, and future development of this versatile technique are discussed.

Lipid nanoparticles (LNPs) are the commonly used delivery tools for messenger RNA (mRNA) therapy and play an indispensable role in the success of COVID-19 mRNA vaccines. Ionizable cationic lipids are the most important component in LNPs. Herein, we developed a series of new ionizable lipids featuring bioreducible disulfide bonds, and constructed a library of lipids derived from dimercaprol. LNPs prepared from these ionizable lipids could be stored at 4 °C for a long term and are non-toxic toward HepG2 and 293T cells. In vivo experiments demonstrated that the best C4S18A formulations, which embody linoleoyl tails, show strong firefly luciferase (Fluc) mRNA expression in the liver and spleen via intravenous (IV) injection, or at the local injection site via intramuscular injection (IM). The newly designed ionizable lipids can be potentially safe and high-efficiency nanomaterials for mRNA therapy.

In July and August of 2022, unprecedented and long-lasting heatwaves attacked central and eastern China (CEC); and the most affected area was in the Yangtze River (YR) basin. The extreme heatwaves and associated drought and wildfire had significant social impacts, but the underlying mechanisms remain unknown. Observational analysis indicates that the heatwaves were regulated by anomalous anticyclone in the mid-upper troposphere over northern CEC. Specifically, the easterly anomalies at the southern flank of the anticyclone caused air isentropic sliding and transported low moist enthalpy (cold and dry) air to the YR basin, contributing to anomalous sinking motions and extreme heatwaves. In comparison, heatwaves were more serious in August than in July due to stronger upper-level anomalous anticyclone and associated easterlies. Importantly, different mechanisms were responsible for the heatwaves in the two months. In July, the relatively weaker anticyclonic anomaly over northern CEC was dominated by the forcing of diabatic heating over northwestern South Asia (NWSA), corresponding with the record-breaking rainfall in and around Pakistan. In August, a powerful anticyclonic condition for the CEC heatwaves originated from an extreme silk road pattern (SRP), superposing the effect of NWSA diabatic heating due to persistent downpour. We notice that another upstream anticyclonic node in the SRP also created heatwaves in Europe. Therefore, the CEC extreme heat was actually associated with other concurrent extremes over the Eurasian continent through large-scale atmospheric teleconnections in 2022.

Scavenger receptor class B type 1 (SR−B1), a multiligand membrane receptor, is expressed in a gradient along the gastrocolic axis. SR−B1 deficiency enhances lymphocyte proliferation and elevates inflammatory cytokine production in macrophages. However, whether SR−B1 affects intestinal metabolites is unclear. In this study, we detected metabolite changes in the intestinal tissue of SR−B1−/− mice, including amino acids and neurotransmitters, by ultra−performance liquid chromatography quadrupole time−of−flight mass spectrometry (UHPLC−Q−TOF/MS) and HPLC. We found that SR−B1−/− mice exhibited changes in intestinal lipid metabolites and metabolic pathways, including the glycerophospholipid, sphingolipid, linoleic acid, taurine, and hypotaurine metabolic pathways. SR−B1 deficiency influenced the contents of amino acids and neurotransmitters in all parts of the intestine; the contents of leucine (LEU), phenylalanine (PHE), tryptophan (TRP), and tyrosine (TYR) were affected in all parts of the intestine; and the contents of 3,4−dihydroxyphenylacetic acid (DOPAC) and dopamine (DA) were significantly decreased in both the colon and rectum. In summary, SR−B1 deficiency regulated intestinal lipids, amino acids, and neurotransmitter metabolism in mice.

Purpose: Coronary artery disease (CAD) and atrial fibrillation (AF) often coexist and lead to a much higher risk of mortality in the elderly population. The aim of this study was to investigate whether the CHA2DS2-VASc score could predict the risk of death in elderly patients with CAD and AF.Methods: Hospitalized patients aged ≥65 years with a diagnosis of CAD and AF were recruited consecutively. Patients were divided into 5 groups according to the CHA2DS2-VASc score (≤2, =3, =4, =5, and ≥6). At least a 1-year follow-up was carried out for the assessment of all-cause death.Results: A total of 1,579 eligible patients were recruited, with 582 all-cause deaths (6.86 per 100 patient-years) occurring during a follow-up of at least 1 year. With the increase in the CHA2DS2-VASc score, the 1-year and 5-year survival rate decreased (96.4% vs. 95.7% vs. 94.0% vs. 86.5% vs. 85.7%, respectively, P < 0.001; 78.4% vs. 68.9% vs. 64.6% vs. 55.5% vs. 50.0%, respectively, P < 0.001). Compared with the patients with CHA2DS2-VASc score

Plant growth is closely related to the structure of its stem. The ultrasonic echo signal of the plant stem carries much information on the stem structure, providing an effective means for analyzing stem structure characteristics. In this paper, we proposed to extract energy features of ultrasonic echo signals to study the structure of the plant stem. Firstly, it is found that there are obvious different ultrasonic energy changes in different kinds of plant stems whether in the time domain or the frequency domain. Then, we proposed a feature extraction method, density energy feature, to better depict the interspecific differences of the plant stems. In order to evaluate the extracted 24-dimensional features of the ultrasound, the information gain method and correlation evaluation method were adopted to compute their contributions. The results showed that the mean density, an improved feature, was the most significant contributing feature in the four living plant stems. Finally, the top three features in the feature contribution were selected, and each two of them composed as 2-D feature maps, which have significant differentiation of the stem species, especially for grass and wood stems. The above research shows that the ultrasonic energy features of plant stems can provide a new perspective for the study of distinguishing the structural differences among plant stem species.

The impacts of the western North Pacific (WNP) tropical cyclone (TC) on East and Southeast Asian inland regions are analyzed. Here, based on a stringent TC selecting criterion, robust increase of TC-related inland impacts between 1979 and 2016 over East and Southeast Asian regions have been detected. The storms sustained for 2–9 h longer and penetrated 30–190 km further inland, as revealed from different best track datasets. The most significant increase of the TC inland impacts occurred over Hanoi and South China. The physical mechanism that affects TC-related inland impacts is shortly discussed. First, the increasing TC inland impacts just occur in the WNP region, but it is not a global effect. Second, besides the significant WNP warming effects on the enhanced TC landfall intensity and TC inland impacts, it is suggested that the weakening of the upper-level Asian Pacific teleconnection pattern since 1970s may also play an important role, which may reduce the climatic 200 hPa anti-cyclonic wind flows over the Asian region, weakening the wind shear near the Philippine Sea, and may eventually intensify the TC intensity when the TCs across the basin. Moreover, the TC inland impacts in the warming future are projected based on a high-resolution (20 km) global model according to the Representative Concentration Pathway 8.5 scenario. By the end of the 21st century, TC mean landfall intensity will increase by 2 m/s (6%). The stronger storms will sustain 4.9 h (56%) longer and penetrate 92.4 km (50%) farther inland, thereby almost doubling the destructive power delivered to Asian inland regions. More inland locations will therefore be exposed to severe storm–related hazards in the future due to warmer climate. Long-term planning to enhance disaster preparedness and resilience in these regions is called for.

Abstract Impacts of urban land cover and anthropogenic heat (AH) on extreme local rainfall over the coastal Pearl River Delta (PRD) megacity region during boreal summer are investigated by conducting numerical experiments using the Weather Research and Forecastingmodel coupled with a single‐layer urban canopy model. To examine the relative importance of land cover change versus the presence of AH, three numerical experiments corresponding to different levels of urbanization in the PRD area were designed: one with cropland covering the whole region, one with urban land cover but zero AH, and one with urban land cover and a strong diurnal maximum of 300 Wm−2 of AH in the model simulations. Results show that the increase of rainfall in the urban area is much more sensitive to the intensity of AH than the mere change of surface properties. Urbanization with intense AH can enhance both the intensity and frequency of extreme rainfall, which can be attributed to higher surface temperature (of about 3.5–4°C), higher convective available potential energy, and lower convective inhibition, thus creating an environment more conducive to strong convection over the urban areas. Moreover, enhanced rainfall is supported by moisture supply from the South China Sea and increased water vapor flux convergence over the PRD city area. The amount of moisture flux converging over the coastal megacity area was found to depend on the direction of prevailing background wind.

Repetitive TMS (rTMS) allows for non-invasive and transient disruption of local neuronal functioning. We used machine learning approaches to assess whether brain tumor patients can be accurately classified into aphasic and non-aphasic groups using their rTMS language mapping results as input features. Given that each tumor affects the subject-specific language networks differently, resulting in heterogenous rTMS functional mappings, we propose the use of machine learning strategies to classify potential patterns of rTMS language mapping results. We retrospectively included 90 patients with left perisylvian world health organization (WHO) grade II-IV gliomas that underwent presurgical navigated rTMS language mapping. Within our cohort, 29 of 90 (32.2%) patients suffered from at least mild aphasia as shown in the Aachen Aphasia Test based Berlin Aphasia Score (BAS). After spatial normalization to MNI 152 of all rTMS spots, we calculated the error rate (ER) in each stimulated cortical area (28 regions of interest, ROI) by automated anatomical labeling parcellation (AAL3) and IIT. We used a support vector machine (SVM) to classify significant areas in relation to aphasia. After feeding the ROIs into the SVM model, it revealed that in addition to age (w = 2.98), the ERs of the left supramarginal gyrus (w = 3.64), left inferior parietal gyrus (w = 2.28) and right pars triangularis (w = 1.34) contributed more than other features to the model. The model’s sensitivity was 86.2%, the specificity was 82.0%, the overall accuracy was 85.5% and the AUC was 89.3%. Our results demonstrate an increased vulnerability of right inferior pars triangularis to rTMS in aphasic patients due to left perisylvian gliomas. This finding points towards a functional relevant involvement of the right pars triangularis in response to aphasia. The tumor location feature, specified by calculating overlaps with white and grey matter atlases, did not affect the SVM model. The left supramarginal gyrus as a feature improved our SVM model the most. Additionally, our results could point towards a decreasing potential for neuroplasticity with age.

Tumors infiltrating the motor system lead to significant disability, often caused by corticospinal tract injury. The delineation of the healthy-pathological white matter (WM) interface area, for which diffusion magnetic resonance imaging (dMRI) has shown promising potential, may improve treatment outcome. However, up to 90% of white matter (WM) voxels include multiple fiber populations, which cannot be correctly described with traditional metrics such as fractional anisotropy (FA) or apparent diffusion coefficient (ADC). Here, we used a novel fixel-based along-tract analysis consisting of constrained spherical deconvolution (CSD)-based probabilistic tractography and fixel-based apparent fiber density (FD), capable of identifying fiber orientation specific microstructural metrics. We addressed this novel methodology’s capability to detect corticospinal tract impairment. We measured and compared tractogram-related FD and traditional microstructural metrics bihemispherically in 65 patients with WHO grade III and IV gliomas infiltrating the motor system. The cortical tractogram seeds were based on motor maps derived by transcranial magnetic stimulation. We extracted 100 equally distributed cross-sections along each streamline of corticospinal tract (CST) for along-tract statistical analysis. Cross-sections were then analyzed to detect differences between healthy and pathological hemispheres. All metrics showed significant differences between healthy and pathologic hemispheres over the entire tract and between peritumoral segments. Peritumoral values were lower for FA and FD, but higher for ADC within the entire cohort. FD was more specific to tumor-induced changes in CST than ADC or FA, whereas ADC and FA showed higher sensitivity. The bihemispheric along-tract analysis provides an approach to detect subject-specific structural changes in healthy and pathological WM. In the current clinical dataset, the more complex FD metrics did not outperform FA and ADC in terms of describing corticospinal tract impairment.

Objective. To identify the clinical characteristics, magnetic resonance imaging (MRI) results, and prognostic factors of neuropsychiatric (NP) systemic lupus erythematosus (SLE; NPSLE) in a relatively large patient series in China. Methods. Data of patients with NPSLE at Peking Union Medical College Hospital (PUMCH) were collected retrospectively from June 2012 to June 2016. NPSLE patients were compared with 220 non-NPSLE patients. Survival rates were evaluated using the Kaplan-Meier curves, log-rank test, and Cox proportional hazards modeling. Cranial MRI results were also studied. Results. Of the 194 included patients, sixteen subtypes of NPSLE were identified, and the most common manifestations were seizure (36.6%), acute confusional state (25.3%), and cerebral vascular disease (15.5%). Compared with the non-NPSLE group, NPSLE patients were significantly more likely to have typical lupus symptoms, higher Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores (P=0.002), and positive rate of anti-ribosomal P protein antibodies (P=0.008). Patients with seizure were more likely to have higher SLEDAI-2K scores and positive anti-β2GP1 than non-NPSLE patients. Sixteen patients died during follow-up. The most common cause of death was infection (37.5%). NPSLE significantly decreased survival rates of SLE patients. Patients with elevated serum creatinine (P=0.001), hypocomplementemia (P=0.031), and SLEDAI−2K scores≥15 (P=0.014) had shorter survival periods. Eighty-two patients underwent detailed cranial MRI analysis; of these, 50 (61.0%) had abnormal results. Small vessel disease was the most common abnormal finding, followed by inflammatory-like lesions and large vessel disease. Conclusions. High disease activity and positive rate of anti-ribosomal P protein antibodies may be risk factors for NPSLE. NPSLE decreases survival rates of SLE patients. Renal insufficiency and high disease activity are predictive of poor prognoses for NPSLE patients.

Background. This study aimed to analyse the role of the HAS-BLED score with the addition of genotype bins for bleeding risk prediction in warfarin-treated patients with atrial fibrillation (AF). Methods and Results. Consecutive patients with AF on initial warfarin treatment were recruited. For each patient, CYP2C9∗3 and VKORC1-1639 A/G genotyping was performed to create 3 genotype functional bins. The predictive values of the HAS-BLED score with or without the addition of genotype bins were compared. According to the carrier status of the genotype bins, the numbers of normal, sensitive, and highly sensitive responders among 526 patients were 64 (12.17%), 422 (80.23%), and 40 (7.60%), respectively. A highly sensitive response was independently associated with clinically relevant bleeding (HR: 3.85, 95% CI: 1.88–7.91, P=0.001) and major bleeding (HR:3.75, 95% CI: 1.17–11.97, P=0.03). With the addition of genotype bins, the performance of the HAS-BLED score for bleeding risk prediction was significantly improved (c-statistic from 0.60 to 0.64 for clinically relevant bleeding and from 0.64 to 0.70 for major bleeding, P

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is undoubtedly the most challenging pandemic in the current century and remains a global health emergency. As the number of COVID-19 cases in the world is on the rise and variants continue to emerge, there is an urgent need for vaccines. Among all immunization approaches, mRNA vaccines have demonstrated more promising results in response to this challenge. Herein, we designed an mRNA-based vaccine encoding the receptor-binding domain (RBD) of SARS-CoV-2 encapsulated in lipid nanoparticles (LNPs). Intramuscular (i.m.) administration of the mRNA-RBD vaccine elicited broad-spectrum neutralizing antibodies and cellular responses against not only the wild-type SARS-CoV-2 virus but also Delta and Omicron variants. These results indicated that two doses of mRNA-RBD immunization conferred a strong immune response in mice against the wild-type SARS-CoV-2, while the booster dose provided a sufficient immunity against SARS-CoV-2 and its variants. Taken together, the three-dose regimen strategy of the mRNA-RBD vaccine proposed in the present study appears to be a promising reference for the development of mRNA vaccines targeting SARS-CoV-2 variants.

Abstract A rapid urbanization process is undergoing in China, exerting significant impacts on local weather and climate. However, rare study pays attention to the underdeveloped regions. An underdeveloped city of Nanning, in southwestern China, is experiencing considerable urbanization. The present urban area of Nanning is 2.8 times larger than that in 1980. Using the Weather Research and Forecasting model coupled with an urban canopy model, two experiments with different urban land use are designed to investigate impacts of Nanning urbanization on a rainstorm occurred in July 2009. Results show simulated precipitation can be significantly improved by the experiment with urbanization effects included. Urbanization leads to a warmer and drier surface, which is favored for the formation of near‐surface low pressure and wind convergence over the city. But the warm‐dry air near urban surface cannot lead to deep convective activity, resulting in urban‐enhanced precipitation is dominated by the large‐scale precipitation. Such enhanced large‐scale precipitation has a positive contribution to atmospheric latent heat release, inducing a heating source in middle troposphere over the urban area. Then the cyclonic circulation around Nanning is intensified according to thermal adaption theory. The enhanced cyclonic circulation is beneficial for stronger moisture convergence and warm‐moist southwesterly flow transports into Guangxi from tropical oceans. Vertical motion is amplified by the coastal orographic uplift effect, and wind convergence over the Nanning downstream is also enhanced. Therefore, the convective precipitation dominantly enhances over the coastal and city's downstream regions, which is different from the urban‐increased large‐scale precipitation in the Nanning City area.

Abstract Pakistan experiences several torrential rainfall events for many years due to interactive role of midlatitude atmospheric and warm moist monsoon circulations. Deadly events such as flash flooding, runoff, and mudslides may trigger by torrential rainfall events which pose significant threat to human assets. This study was undertaken based on three severe weather events (1988, 2010, and 2013) by using percentage departure to identify wet and dry years during the period 1985–2016, which occurred over northern Pakistan. Rainfall data were obtained from 14 synoptic stations of Pakistan Meteorological Department, which were analyzed at daily, monthly, and annual bases. The data sets of Climate Research Unit, Global Precipitation Climatology Centre, and Pakistan Meteorological Department are used to justify the Weather Research and Forecasting model simulation and for analyzing the various atmospheric and diagnostic variables. Results showed teleconnection between large‐scale circulation pattern and South Asian summer monsoon during the selected events. Detailed analysis revealed that during all three events, a westerly trough was moving in the north of Pakistan and well‐marked monsoon circulations were present at the lower levels. It was observed that the interaction of two weather systems triggered heavy rainfall over area of interest. In addition, high vorticity at all levels and extension of westerly trough to the surface resulted in heavy rainfall and the penetration of upper‐level circulations anomalies consists of blocking signature over Eurasia along with Tibetan anticyclone. Hence, the monsoon low‐pressure system provides moisture convergence and upper‐level westerly trough results in upper‐level divergence to enhance the extreme rainfall events.