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Background. Platelets play parts in infection and immune processes. However, the association between platelet count and the risk of peritoneal dialysis-associated peritonitis is unclear. Methods. This was a retrospective, observational, single-center cohort study. A Cox regression analysis was used to evaluate the independent association of platelet count with the occurrence of first PD-associated peritonitis. Models were adjusted for gender, age, BMI, cardiovascular disease, diabetes mellitus, white blood cell count, neutrophil-lymphocyte ratio, hemoglobin level, albumin level, potassium level, and anti-platelet medication usage. Results. A total of 2374 patients were enrolled in this study (59% men; mean age 47.40 ± 12.12). The average platelet count was 229.30±82.12 x 109/L. 467 (20%) patients suffered from PD-associated peritonitis at least once. In the multivariable model, the adjusted hazard ratios (HRs) for quartiles 2, 3 and 4 versus quartile 1 were 1.428 (95% CI 1.060-1.924, P=0.019), 1.663 (95% CI 1.240-2.229, P

Urban form contributes to crime prevention. However, most studies not only simplify the relationship between urban form and crime, they also fail to reflect the geographic structure of urban areas. This study first measured a comprehensive multidimensional urban form indicator for 1486 counties in the United States, which was used to characterize the size and geospatial structure of urban areas. Specifically, it described urban form as consisting of three components: 1) size and population distribution; 2) built environment; and 3) landscape environment. Then, generalized additive mixed models were then used to explore linear or nonlinear associations between urban form indicators and different crime types (violent and property crime). This study's main findings were that 1) the relationship between urban form and crime is not only linear but may also be nonlinear; 2) urban size, fragmentation, connectivity, forest mixing, and shrub mixing are associated with all crime types; 3) population distribution and agricultural mixing are associated with violent crime; and 4) urban patch complexity and water mixing are associated with property crime. Overall, the results of this study can provide guidance for long-term planning of urban geographic structures, contributing to the safe and sustainable development of urban areas.

Hydraulic fracturing is a widely used technique for increasing the permeability of coal seams. Its impact on the production capacity of coalbed methane(CBM) wells is significant. This paper makes detailed observations on the exposed coal seams and fracture distribution of 5 CBM wells in Tunlan block of Xishan coalfield, and studies the distribution characteristics of coal structure, microfractures, quartz sand and coal fine by using stereoscopic microscope, scanning electron microscope, and micro CT. The fracturing effect and influencing factors of CBM wells are analysed by combining regional geostress and hydraulic fracturing construction parameters. The research results indicate that the macroscopic fractures morphology produced by hydraulic fracturing are complex and diverse, including horizontal, vertical, X and T-shaped fractures. The degree of coal body fragmentation increases with distance from the CBM well. The coal body closer to the CBM well is mainly composed of fragmented and granular coal, while the coal body further away is mainly composed of undeformed coal with primary fractures. The quartz sands are mainly deposited in horizontal fractures, with only a small amount in T-shaped fractures. Quartz sand rubs, collides, and embeds strongly with the coal fracture surface. The fracturing fluid is then superimposed to fracture the coal body, resulting in a large amount of coal fines. This causes the coal fines to wrap around the quartz sand and block the fractures. The coal fines within the macroscopic fracture are primarily a result of the fracturing of the coal body, the flushing of the coal body by fracturing fluid, and the friction between the quartz sand and the fracture surface during hydraulic fracturing. Coal fine generation in micro-fractures during coal body fracturing. Coal fines and quartz sand accumulate in the fractures, creating enormous resistance to the carrying fluid and preventing the quartz sand from migrating to the far end of the CBM well. The magnitude and direction of the geostress, as well as the strength of the coal seam roof and floor, are important factors that influence the opening and direction of the hydraulic fracturing fractures. The low viscosity of the carrying fluid cannot suspend quartz sand, and the accumulation of quartz sand and coal fine can block the fractures, easy to cause quartz sand and coal fine to aggregate and block fractures.

Abstract Cultural heritage is an important contributor to sustainable urban development, and its conservation is considered a global task. Previous research has primarily focused on the conservation of heritage buildings within architectural contexts and world heritage sites within geographical contexts. However, there is a notable gap in conservation of green cultural heritage (GCH) within a landscape-based framework. This study used the extended theory of planned behavior to explore the factors and pathways that influence the public's behavioral intentions toward GCH conservation. Based on 1075 questionnaires collected in Tokyo, Japan, the hypotheses of the newly constructed theoretical model were tested using partial least squares structural equation modeling. The results show that perceived behavioral control has the greatest positive influence on citizens' GCH conservation intentions and behaviors, while social norms do not influence people's behavioral intention to conserve. In the extended factors, the environmental awareness which including heritage awareness and cultural attachment, significantly influences public attitudes towards conservation. Additionally, environmental perception, including perceived usefulness and perceived quality, significantly affects the public's conservation intentions and behaviors, respectively. Our findings have implications for local governments and policymakers to enhance public participation in GCH, as well as some several new theoretical interests for further studies.

Abstract Background Appropriate physical activity (PA) and good sleep are beneficial to maternal and fetal health. This paper sought to explore the associations of PA and sleep quality among healthy women at the first and second trimesters of pregnancy on mental health and pregnancy outcomes. Methods Totally 268 healthy pregnant women were retrospectively analyzed as study subjects, 134 each in the first trimester (FT) and second trimester (ST). Their baseline clinical data were obtained respectively at two stages of pregnancy. The PA/sleep quality of subjects were assessed through the Pregnancy Physical Activity Questionnaire-Chinese version (PPAQ-C)/Pittsburgh Sleep Quality Index (PSQI) scale. The mental health was assessed via the Hospital Anxiety and Depression Scale (HADS). The correlations of PA and sleep quality with mental health were analyzed using Spearman correlation analysis. Pregnancy outcomes of all subjects, associations of moderate intensity (MI) PA and sleep quality with adverse pregnancy outcomes, and independent influencing factors for adverse outcomes were analyzed. Results Pregnant women in the ST group exhibited higher levels of MI, worse sleep quality, and lower levels of anxiety and depression than those in the FT group. Anxiety and depression were negatively correlated with MI but positively linked with PSQI scores at the first and second trimesters. MI ≥ 7.5 MET-h/week and good sleep quality were associated with a reduced incidence of adverse pregnancy outcomes. Conclusion MI ≥ 7.5 MET-h/week and good sleep quality at the first and second trimesters of pregnancy benefit mental health and markedly reduce the occurrence of adverse pregnancy outcomes.

Abstract Background This study explores prognostic factors influencing Vogt-Koyanagi-Harada (VKH) disease and observes the efficacy and safety of Adalimumab (ADA) in treating recurrence in Vogt-Koyanagi-Harada (VKH) patients. Methods A retrospective study was conducted on all patients diagnosed with VKH disease at Beijing Tongren Hospital between 2020 and 2023. Clinical data included initial and final visual acuity, age, gender, ocular complications, treatment modalities, disease duration, and recurrence frequency. Results A total of 62 VKH patients were included, comprising 34 in the acute-resolved group and 28 in the chronic-recurrent group. The mean age of patients in the acute-resolved group was 38.29 ± 15.46 years, while the mean age of chronic-recurrent group had a 49.00 ± 16.43 years. Initial best-corrected visual acuity (BCVA) examination at the first visit showed an average BCVA of 0.64 ± 0.29 logMAR in the acute-resolved group and 1.38 ± 0.54 logMAR in the chronic-recurrent group (p = 0.002). During follow-up, ocular complications were observed in 29.4% of the acute-resolved group patients and 41.7% of the chronic-recurrent group patients (P = 0.006). “Sunset glow fundus” was observed in 23.5% of the acute-resolved group and 64.3% of the chronic-recurrent group patients (P = 0.001). Poor initial BCVA (P = 0.046) and the occurrence of “sunset glow fundus” (P = 0.040) were significantly associated with progression to the chronic recurrent phase. Logistic regression analysis revealed that older age at onset (P = 0.042) and the occurrence of “sunset glow fundus” (P = 0.037) were significant predictors for progression to the chronic recurrent phase. ADA significantly reduced anterior chamber inflammatory cells (P = 0.000) and vitreous cavity inflammatory cells (P = 0.001) in the chronic-recurrent group, and markedly decreased the recurrence rate in VKH patients (P = 0.009). Conclusion In comparison to acute-resolved patients, chronic-recurrent patients exhibited poorer initial BCVA and a significantly increased incidence of “sunset glow fundus.” Older age at onset and the occurrence of “sunset glow fundus” at diagnosis are crucial predictive factors for VKH patients progressing to the chronic recurrent phase. ADA effectively alleviates refractory VKH disease and is generally well-tolerated.

Abstract The anomalous Hall effect (AHE) and its thermoelectric counterpart, the anomalous Nernst effect (ANE), are two transverse transport coefficients that are intensely studied in condensed matter physics. While conventional wisdom links AHE and ANE to ferromagnetism, recent achievements reveal that they can emerge in nonmagnetic and antiferromagnetic topological materials with a diversity of mechanisms—many of which await further elucidation. Here, both an unconventional AHE (UAHE) that does not scale with the magnetization and a sizable ANE ( ≈ 1.8 μV K−1) are shown to be possessed by the metallic tetragonal antiferromagnet SmMnBi2. Electronic band structure of SmMnBi2 is investigated by angle-resolved photoemission spectroscopy and first-principles calculations. It is demonstrated that the UAHE reflects the intrinsic Berry curvature contribution stemming from the spin-canted antiferromagnetism, whereas the ANE is possibly further amplified by extrinsic mechanisms. These results identify SmMnBi2 as a promising candidate for exploring unusual transverse transport effects and the extremely rich underlying physics.

Introduction: Breast cancer (BC) is a malignant disease that occurs worldwide and poses serious health burden. Objectives: To assess the prevalence of BC burden in the Western Pacific region (WPR) from 1990 to 2019, and to predict trends from 2020 to 2044. To analyze the driving factors and put forward the region-oriented improvement. Methods: Based on the Global Burden of Disease Study 2019, BC cases, deaths, disability-adjusted life years (DALYs) cases, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALYs rate in WPR from 1990 to 2019 was obtained and analysed. Age-period-cohort (APC) model was used to analyze age, period, and cohort effects in BC, and Bayesian APC (BAPC) was used to predict trends over the next 25 years. Results: In conclusion, BC incidence and deaths in the WPR have increased rapidly over the past 30 years and are expected to continue to increase between 2020 and 2044. Among behavioral and metabolic factors, high body-mass index was the main risk factor for BC mortality in middle-income countries, whereas alcohol use was the main risk factor in Japan. Age is a key factor in the development of BC, with 40 years being the critical point. Incidence trends coincide with the course of economic development. Conclusions: The BC burden remains an essential public health issue in the WPR and will increase substantially in the future. More efforts should be made in middle-income countries to prompt the health behavior and minimize the burden of BC because these nations accounts for the majority of BC burden in the WPR.

The combination of biochar and nitrogen (N) fertilization in agricultural salt-affected soils is an effective strategy for amending the soil and promoting production. To investigate the effect of nitrogen reduction combined with biochar application on a soda saline soil and soybean growth in black soil areas, a pot experiment was set up with two biochar application levels, 0 (B0) and 4.5 t/hm2 (B1); two biochar application depths, 0-20 cm (H1) and 0-40 cm (H2); and two nitrogen application levels, conventional nitrogen application (N0) and nitrogen reduction of 15% (N1). The results showed that the application of biochar improved the saline soil status and significantly increased soybean yield under lower nitrogen application. Moreover, increasing the depth of biochar application enhanced the effectiveness of biochar in reducing saline soil barriers to crop growth, which promoted soybean growth. Increasing the depth of biochar application increased the K+ and Ca2+ contents, soil nitrogen content, N fertilizer agronomic efficiency, leaf total nitrogen, N use efficiency, AN, Tr, gs, SPAD, leaf water potential, water content and soybean yield and its components. However, the Na+ content, SAR, ESP, Na+/K+, Ci and water use efficiency decreased with increasing biochar depth. Among the treatments with low nitrogen input and biochar, B1H1N1 resulted in the greatest soil improvement in the 0-20 cm soil layer compared with B0N0; for example, K+ content increased by 61.87%, Na+ content decreased by 44.80%, SAR decreased by 46.68%, and nitrate nitrogen increased by 26.61%. However, in the 20-40 cm soil layer, B1H2N1 had the greatest effect on improving the soil physicochemical properties, K+ content increased by 62.54%, Na+ content decreased by 29.76%, SAR decreased by 32.85%, and nitrate nitrogen content increased by 30.77%. In addition, compared with B0N0, total leaf nitrogen increased in B1H2N1 by 25.07%, N use efficiency increased by 6.7%, N fertilizer agronomic efficiency increased by 32.79%, partial factor productivity of nitrogen increased by 28.37%, gs increased by 22.10%, leaf water potential increased by 27.33% and water content increased by 6.44%. In conclusion, B1H2N1 had the greatest effect on improving the condition of saline soil; it not only effectively regulated the distribution of salt in soda saline soil and provided a low-salt environment for crop growth but also activated deep soil resources. Therefore, among all treatments investigated in this study, B1H2N1 was considered most suitable for improving the condition of soda saline soil in black soil areas and enhancing the growth of soybean plants.

Van Gogh-like 2 (Vangl2), a core planar cell polarity component, plays an important role in polarized cellular and tissue morphology induction, growth development, and cancer. However, its role in regulating inflammatory responses remains elusive. Here, we report that Vangl2 is upregulated in patients with sepsis and identify Vangl2 as a negative regulator of The nuclear factor-kappaB (NF-κB) signaling by regulating the protein stability and activation of the core transcription component p65. Mice with myeloid-specific deletion of Vangl2 (Vangl2ΔM) are hypersusceptible to lipopolysaccharide (LPS)-induced septic shock. Vangl2-deficient myeloid cells exhibit enhanced phosphorylation and expression of p65, therefore, promoting the secretion of proinflammatory cytokines after LPS stimulation. Mechanistically, NF-κB signaling-induced-Vangl2 recruits E3 ubiquitin ligase PDLIM2 to catalyze K63-linked ubiquitination on p65, which serves as a recognition signal for cargo receptor NDP52-mediated selective autophagic degradation. Taken together, these findings demonstrate Vangl2 as a suppressor of NF-κB-mediated inflammation and provide insights into the crosstalk between autophagy and inflammatory diseases.

Tribbles pseudokinase 3 (TRIB3) expression significantly increases during terminal erythropoiesis in vivo. However, we found that TRIB3 expression remained relatively low during human embryonic stem cell (hESC) erythropoiesis, particularly in the late stage, where it is typically active. TRIB3 was expressed in megakaryocyte-erythrocyte progenitor cells and its low expression was necessary for megakaryocyte differentiation. Thus, we proposed that the high expression during late stage of erythropoiesis could be the clue for promotion of maturation of hESC-derived erythroid cells. To our knowledge, the role of TRIB3 in the late stage of erythropoiesis remains ambiguous. To address this, we generated inducible TRIB3 overexpression hESCs, named TRIB3tet-on OE H9, based on a Tet-On system. Then, we analyzed hemoglobin expression, condensed chromosomes, organelle clearance, and enucleation with or without doxycycline treatment. TRIB3tet-on OE H9 cells generated erythrocytes with a high proportion of orthochromatic erythroblast in flow cytometry, enhanced hemoglobin and related protein expression in Western blot, decreased nuclear area size, promoted enucleation rate, decreased lysosome and mitochondria number, more colocalization of LC3 with LAMP1 (lysosome marker) and TOM20 (mitochondria marker) and up-regulated mitophagy-related protein expression after treatment with 2 μg/mL doxycycline. Our results showed that TRIB3 overexpression during terminal erythropoiesis may promote the maturation of erythroid cells. Therefore, our study delineates the role of TRIB3 in terminal erythropoiesis, and reveals TRIB3 as a key regulator of UPS and downstream mitophagy by ensuring appropriate mitochondrial clearance during the compaction of chromatin.

The accumulation of toxic elements from sediments poses imminent threats to both the environment and humans. The variation of elements in different sedimentary systems within the same watershed is of significant importance for distinguishing the human activities and adopting relevant management strategies. Based on the surface sediment samples from the Lake Keluke and its wetland, the content and grain size of elements were analyzed. The human health risk indicated in the area the potentially toxic elements (PTEs: Cr, Cu, Zn, Cd and Pb) were at no non-carcinogenic risk to adults or children. Except for Cd, the pollution levels of other PTEs were clean, and potential ecological risk with a low level. However, the pollution of Cd implicated a moderate to heavy pollution intensity and a high ecological risk. According to principal component analysis (PCA), and self-organizing maps (SOM), the main sources of PTEs were of the weathering and leaching of bedrocks; transportation and human agriculture activities. The watershed should reduce pollution caused by human activities and implement efficient agricultural practices.

Abstract Toxoplasma gondii (T. gondii)‐associated polymorphic effector proteins are crucial in parasite development and regulating host anti‐T. gondii immune responses. However, the mechanism remains obscure. Here, it is shown that Toxoplasma effector dense granules 4 (GRA4) restricts host IFN‐I activation. Infection with Δgra4 mutant T. gondii strain induces stronger IFN‐I responses and poses a severe threat to host health. Mechanistically, GRA4 binds to phosphorylated TBK1 to promote TRIM27‐catalyzed K48‐ubiquitination at Lys251/Lys372 residues, which enhances its recognition by autophagy receptor p62, ultimately leading to TBK1 autophagic degradation. Furthermore, an avirulent Δgra4 strain (ME49Δompdc/gra4) is constructed for tumor immunotherapy due to its ability to enhance IFN‐I production. Earlier vaccination with ME49Δompdc/gra4 confers complete host resistance to the tumor compared with the classical ME49Δompdc treatment. Notably, ME49Δompdc/gra4 vaccination induces a specific CD64+MAR‐1+CD11b+ dendritic cell subset, thereby enhancing T cell anti‐tumor responses. Overall, these findings identify the negative role of T. gondii GRA4 in modulating host IFN‐I signaling and suggest that GRA4 can be a potential target for the development of T. gondii vaccines and tumor immunotherapy.

Abstract Decreased plasma spermine levels are associated with kidney dysfunction. However, the role of spermine in kidney disease remains largely unknown. Herein, it is demonstrated that spermine oxidase (SMOX), a key enzyme governing polyamine metabolism, is predominantly induced in tubular epithelium of human and mouse fibrotic kidneys, alongside a reduction in renal spermine content in mice. Moreover, renal SMOX expression is positively correlated with kidney fibrosis and function decline in patients with chronic kidney disease. Importantly, supplementation with exogenous spermine or genetically deficient SMOX markedly improves autophagy, reduces senescence, and attenuates fibrosis in mouse kidneys. Further, downregulation of ATG5, a critical component of autophagy, in tubular epithelial cells enhances SMOX expression and reduces spermine in TGF‐β1‐induced fibrogenesis in vitro and kidney fibrosis in vivo. Mechanically, ATG5 readily interacts with SMOX under physiological conditions and in TGF‐β1‐induced fibrogenic responses to preserve cellular spermine levels. Collectively, the findings suggest SMOX/spermine axis is a potential novel therapy to antagonize renal fibrosis, possibly by coordinating autophagy and suppressing senescence.

Plant height influences plant architecture, lodging resistance, and yield performance. It is modulated by gibberellic acid (GA) metabolism and signaling. DELLA proteins, acting as central repressors of GA signaling, integrate various environmental and hormonal signals to regulate plant growth and development in Arabidopsis. We examined the role of two DELLA proteins, GmRGAa and GmRGAb, in soybean plant height control. Knockout of these proteins led to longer internodes and increased plant height, primarily by increasing cell elongation. GmRGAs functioned under different light conditions, including red, blue, and far-red light, to repress plant height. Interaction studies revealed that GmRGAs interacted with the blue light receptor GmCRY1b. Consistent with this, GmCRY1b partially regulated plant height via GmRGAs. Additionally, DELLA proteins were found to stabilize the protein GmSTF1/2, a key positive regulator of photomorphogenesis. This stabilization led to increased transcription of GmGA2ox-7b and subsequent reduction in plant height. This study enhances our understanding of DELLA-mediated plant height control, offering Gmrgaab mutants for soybean structure and yield optimization.

In order to explore the fracturing characteristics of coalbed methane wells in the Tunlan block, the No.2 coal seam in the Tunlan block, Xishan, Taiyuan was taken as the research object. The fracturing characteristics of the coal seams from multiple scales was studied through geological cataloguing, macroscopic characterization of coal samples and CT (Computed Tomography) analysis for four coal bed methane wells of XST-167, XST-168, XST-176 and XST-177, which were exposed at the coal mining face. The results shown that, the coal seam near the wells in the study area were mainly distributed with “X” type fractured fractures consisting of diagonally intersecting fractures, and there were “T” type fractured fractures near the XST-177 coalbed methane well. Collision and friction of quartz sand with fractured fracture walls produced pulverized coal, which filled in the fracture and hindered the output of coalbed methane. By comparing the drill holes exposed by the two coalbed methane wells of XST-168 and XST-177, it was found that the fracturing effect of the XST-177 coalbed methane well was better and more conductive to the output of coalbed methane. Most of the coals near coalbed methane wells were fragmented and crushed coal, and hydraulic fracturing destroyed the original structure of coal, which reduced the hardness of coal and significantly increased the cracks. Embedded quartz sand can be observed on some of the coal samples, which was mainly concentrated on the bedding surface, indicating that the quartz sand, after being pressed into the coal seam, mainly extended into the seam along the horizontal fracture, which was consistent with the direction of the maximum principal stress. By CT scanning technology, the coal samples affected by fracturing (fractured coal) and not affected by fracturing (normal coal) were scanned. It was found that, the fractures with a width greater than 100 μm in the fractured coals of T1 and T2 accounted for 58.8% and 48.5% of the total fracture volume, and the numbers of the fractures was 23407 and 19679, respectively. In normal coal T3, the fractures with width greater than 100 μm only accounted for 1.7% of the total fracture volume, and the number of fractures was only 3504. The width of the fractures in T1 and T2 was wider and the number of fractures was more than that in T3, which indicated that the width and number of fractures in the coal sample were significantly increased by the fracturing action, and the pores and fractures in the fractured coal were more developed.

Abstract With the development of next-generation sequencing technology, de novo variants (DNVs) with deleterious effects can be identified and investigated for their effects on birth defects such as congenital heart disease (CHD). However, statistical power is still limited for such studies because of the small sample size due to the high cost of recruiting and sequencing samples and the low occurrence of DNVs. DNV analysis is further complicated by genetic heterogeneity across diseased individuals. Therefore, it is critical to jointly analyze DNVs with other types of genomic/biological information to improve statistical power to identify genes associated with birth defects. In this review, we discuss the general workflow, recent developments in statistical methods, and future directions for DNV analysis.

Abstract Kagome superconductors AV3Sb5 (A = K, Rb and Cs) have attracted much recent attention due to the coexistence of multiple exotic orders. Among them, the charge density wave (CDW) order has been shown to host various unconventional behaviors. Here, we investigate the CDW order by a combination of both bulk and surface doping methods. While element substitutions in bulk doping change both carriers and the crystal lattice, the surface doping primarily tunes the carrier concentration. As such, our results reveal a two-dimensional phase diagram of the CDW in doped CsV3Sb5. In the lightly bulk doped regime, the existence of CDW order is reversible by tuning the carrier concentration. But excessive bulk doping permanently destroys the CDW, regardless of the carrier doping level. These results provide insights to the origin of the CDW from both electronic and structural degrees of freedom. They also open an avenue for manipulating the exotic CDW order in Kagome superconductors.

Abstract Background Head and neck squamous carcinoma (HNSCC) is known for its high aggressiveness and susceptibility to cervical lymph node metastasis, which greatly contributes to its poor prognosis. During tumorigenesis, many types of cancer cells acquire oncogenic super-enhancers (SEs) that drive the overexpression of oncogenes, thereby maintaining malignant progression. This study aimed to identify and validate the role of oncogenic SE-associated genes in the malignant progression of HNSCC. Methods We identified HNSCC cell-specific SE-associated genes through H3K27Ac ChIP-seq and overlapped them with HNSCC-associated genes obtained from The Cancer Genome Atlas (TCGA) dataset and Gene Expression Omnibus (GEO) datasets using weighted gene coexpression network analysis (WGCNA) to identify hub genes. The expression of IGF2BP2 and KLF7 in HNSCC was detected using clinical samples. To determine the biological role of IGF2BP2, we performed CCK-8, colony formation assay, Transwell migration assay, invasion assay, and orthotopic xenograft model experiments. Furthermore, we utilized a CRISPR/Cas9 gene-editing system, small-molecule inhibitors, ChIP-qPCR, and dual-luciferase reporter assays to investigate the molecular mechanisms of IGF2BP2 and its upstream transcription factors. Results Our study identified IGF2BP2 as a hub SE-associated gene that exhibited aberrant expression in HNSCC tissues. Increased expression of IGF2BP2 was observed to be linked with malignant progression and unfavorable prognosis in HNSCC patients. Both in vitro and in vivo experiments confirmed that IGF2BP2 promotes the tumorigenicity and metastasis of HNSCC by promoting cell proliferation, migration, and invasion. Mechanistically, the IGF2BP2-SE region displayed enrichment for H3K27Ac, BRD4, and MED1, which led to the inhibition of IGF2BP2 transcription and expression through deactivation of the SE-associated transcriptional program. Additionally, KLF7 was found to induce the transcription of IGF2BP2 and directly bind to its promoter and SE regions. Moreover, the abundance of KLF7 exhibited a positive correlation with the abundance of IGF2BP2 in HNSCC. Patients with high expression of both KLF7 and IGF2BP2 showed poorer prognosis. Lastly, we demonstrated that the small molecule inhibitor JQ1, targeting BRD4, attenuated the proliferation and metastatic abilities of HNSCC cells. Conclusions Our study reveals the critical role of IGF2BP2 overexpression mediated by SE and KLF7 in promoting HNSCC progression. Targeting SE-associated transcriptional programs may represent a potential therapeutic strategy in managing HNSCC.

Abstract Background and aims Severe acute pancreatitis (SAP) is potentially lethal. Considering the role of inflammation in the progression of acute pancreatitis (AP), this study aims to develop a model based on inflammatory indexes for identifying the presence of SAP. Methods Overall, 253 patients with AP who were consecutively admitted between July 2018 and November 2020 were screened, of whom 60 had SAP. Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-platelet ratio (NPR), systemic inflammation response index (SIRI), platelet-to-albumin ratio (PAR), C-reactive protein-to-albumin ratio (CAR), C-reactive protein-to-lymphocyte ratio (CLR), and triglyceride glucose (TyG) index were calculated. Multivariate logistic regression analyses were performed to identify independent risk factors of SAP. Then, inflammation-based models were established. Receiver operating characteristics (ROC) curve analyses were performed. Area under ROC curve (AUROC) was calculated. Results Diabetes mellitus, fatty liver, high white blood cell count (WBC), C-reactive protein (CRP), red blood cell distribution width (RDW), procalcitonin (PCT), SII, NLR, NPR, CAR, CLR, and TyG index, and a low LMR were significantly associated with SAP. Considering the collinearity among these variables, 10 multivariate logistic regression analyses were separately performed. Finally, four independent inflammation-based models were established. Of them, the best one, which was calculated as follows: 1.204*fatty liver (yes = 1; no = 0) + 0.419*PCT + 0.005*CLR - 2.629, had an AUROC of 0.795 with a specificity of 73.4% and a sensitivity of 71.7%. Conclusion The inflammation-based model consisting of fatty liver, PCT, and CLR has a good diagnostic performance for SAP.

The size and shape of rice grains influence their yield and commercial value. We investigated the role of OsDA1, a rice homolog of the Arabidopsis DA1 gene, in regulating grain size and shape. OsDA1 was highly expressed in young spikelets and glumes. Its overexpression led to enlarged seeds with increased width and decreased length/width ratio (LWR) and knocking out OsDA1 reduced grain width and increased grain length and LWR. A R310K point mutation in the DA1-like domain is a potential target for breeding for increased grain width and length. OsDA1 interacted with TCP gene-family proteins to regulate grain size and shape. Our findings deepen our understanding of the molecular mechanisms underlying grain size regulation and provide useful information for improving grain yield.

Objective: To evaluate the accuracy of contrast-enhanced ultrasound (CEUS) for the diagnosis of axillary lymph nodes in breast cancer. Methods: PubMed, EMBASE, The Cochrane Library, Chinese Biomedical Literature Database, the full database of China, Chinese National Knowledge Infrastructure, and Wanfang database databases were utilized. Perspective studies regarding CEUS diagnosis of axillary lymph nodes in breast cancer were included. QUADAS-2 was used to estimate the research quality by two reviewers independently. Metadisc1.4 software and Stata 14.0 were used to examine data from the included studies. The diagnostic value of CEUS was assessed by aspects such as summary sensitivity, specificity, receiver operating characteristic (SROC). Results: Fourteen studies were included and 1127 patients were included. A meta-analysis showed that the summary sensitivity of CEUS was 0.85 (95 % CI 0.82–0.87), the specificity was 0.86 (95 % CI 0.82–0.89), the diagnostic odds ratio was 31.15 (95 % CI 17.16–56.52) and the SROC was 0.9186. Conclusions: CEUS diagnosis of axillary lymph nodes in breast cancer has high sensitivity and specificity and it is the preferred method to diagnose axillary lymph nodes in breast cancer in clinical practice.

The study aimed to identify the independent prognostic factors of mixed endometrial carcinoma (MEC) patients treated with hysterectomy and to explore the optimal treatment modalities for overall survival (OS) and cancer-specific survival (CSS). Using the Surveillance, Epidemiology, and End Results (SEER) database, a total of 12,848 MEC patients treated with hysterectomy were screened out. Independent prognostic factors were identified by Cox regression analysis and used to construct the nomogram. The concordance index (C-index) of OS and CSS were 0.807 and 0.834 in the training set. Validation of the nomogram revealed that the receiver operating curve (ROC) maintained good discrimination, the decision curve analysis (DCA) had a high net benefit rate, and the calibration curves showed high consistency. Patients were grouped by the nomogram formula and the number of positive regional lymph nodes (NPR-Lymph node) to evaluate the therapeutic outcomes of chemotherapy, radiotherapy, neoadjuvant treatment and lymph node operation. Survival analysis revealed that chemotherapy could improve the prognosis for OS and CSS in the high-risk group and in the group with NPR-Lymph node counts above 1 (P < 0.05). Radiotherapy was associated with better OS and CSS in the intermediate-risk and high-risk groups, and in the group with NPR-Lymph node counts above 0 (P < 0.05). Lymphadenectomy was found to prolong OS and CSS in the high-risk group (P < 0.05), while neoadjuvant treatment did not prolong OS and CSS in any group. Thus, in this study, the nomogram for MEC patients treated with hysterectomy was successfully built and validated which could effectively predict the prognosis and identify at-risk population to guide clinical decision-making. The NPR-Lymph node was identified as a potentially strong prognostic indicator with good clinical value.

ObjectiveThe objective of this research was to introduce, translate, and verify the Patient Participation Scale (PPS) within a Chinese context.MethodsWe applied a combination of internal consistency testing, item analysis, exploratory factor analysis, and confirmatory factor analysis. The research involved 453 individuals, comprising both outpatients and inpatients, across three Jinzhou Medical University-affiliated hospitals in China. Additionally, a subgroup of 50 patients underwent a retest after a 2-week interval to assess reliability.ResultsThe adapted Chinese edition of the PPS included 21 items. Exploratory factor analysis identified four distinct factors, accounting for 66.199% of the total variance. Confirmatory factor analysis supported a suitable four-factor structure (χ/df: 2.045, RMSEA: 0.048, GFI: 0.935, AGFI: 0.914, TLI: 0.958, CFI: 0.965, and PGFI: 0.712). The factor loadings corresponded to each item exceeded 0.6, the average variance extracted (AVE) exceeded 0.5, and the composite reliability (CR) exceeded 0.7. The correlation coefficients stayed below the square root of the AVE, demonstrated relatively favourable convergent and discriminant validity.The Chinese PPS edition demonstrated high internal consistency (Cronbach’s alpha: 0.919), with dimensional Cronbach’s alpha ranged from 0.732 to 0.918. Split-half as well as retest reliabilities were recorded at 0.737 and 0.864, respectively. The content validity index for the Chinese PPS edition stood at 0.974.ConclusionThe Chinese edition of the PPS emerges as a valid and reliable tool for assessing patient engagement in their own treatment as well as care, applicable in both inpatient as well as outpatient settings.

In the emerging post-pandemic era (the ‘wavelet’ era), humans must coexist with viruses for the foreseeable future, and personal protective behaviors will largely replace national-level preventive measures. In this new normal, encouraging the public to implement proper personal protective behaviors against the coronavirus disease (COVID-19) is vital to the sustainable development of cities and communities. This knowledge–attitude–practice (KAP) survey conducted in Chengdu (N = 900) narrowed the knowledge gap regarding post-pandemic public practices of protective behavior. Findings show that:(1) approximately 1/3 of the respondents are currently not concerned about COVID-19 at all; (2) respondents with different demographics and individual COVID-19-related factors showed significant differences in practice behaviors indoors and outdoors; (3) vulnerable groups performed better in practice behavior indoors/outdoors; (4) because the public may relax their vigilance outdoors, public places may become a transmission threat in the next outbreak; (5) attitudes are important, but limited incentives for practice; and (6) when knowledge increases beyond a threshold (68.75–75% in this study), protective behaviors decrease. Our results suggest that authorities must continue to educate and motivate the public, extending measures to cover personal protective practices, and have targeted policies for specific demographics to ensure equity in healthcare in the event of another pandemic (COVID-19 and alike crisis). Besides, comparing the results of the current study with similar studies conducted in other parts of the world can provide insights into how different populations respond to and adopt COVID-19 protective behaviors. The epidemiologists can use the data collected by this and other KAP surveys to refine epidemiologic models, which can help predict the spread of the virus and the impact of interventions in different settings.

IntroductionChronic diseases are becoming a serious threat to the physical and mental health of older people in China as their aging process picks up speed. Home hospice care addresses diverse needs and enhances the quality of life for older adult individuals nearing the end of life. To ensure the well-being of chronically ill older adults at the end of life, it is vital to explore and assess the multidimensional hospice needs of terminally ill older individuals in their homes. The aim of this study was to investigate the current situation of home hospice care needs of Chinese older adults with chronic diseases at the end of life, and to analyze the influencing factors (sociodemographic and disease-related factors).MethodsIn this cross-sectional study, 247 older adult people with chronic diseases at the end of life were selected from the communities of 4 community health service centers in Jinzhou City, Liaoning Province from June to October 2023 by random sampling method. A general information questionnaire and the home hospice care needs questionnaire developed by our research group were used to investigate. Independent samples t-test or one-way ANOVA was used to compare the differences in the scores of different characteristics, and the factors with significant differences were selected for multivariate linear regression analysis to determine the final influencing factors.ResultsThe total score of home hospice needs of the dying older adult was 115.70 ± 12, with the mean scores for each dimension in descending order being Information Needs (3.96 ± 0.61), Social Support Needs (3.96 ± 0.44), Spiritual Needs (3.92 ± 0.43), Physical Needs (3.60 ± 0.59), Psychological Needs (3.37 ± 0.65). Status of residence, duration of illness (year), the type of disease, and self-care ability were influential factors in the total score of home hospice needs.DiscussionThe need for hospice care for the terminally ill older adult is high, and healthcare professionals should implement services according to the influencing factors of need to meet their multidimensional needs and improve their quality of life.

BackgroundImmunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is frequently accompanied with type 1 autoimmune pancreatitis (AIP). Isolated IgG4-SC which is not accompanied with AIP is uncommon in clinical practice, and its manifestations are similar to those of hilar cholangiocarcinoma.Case presentationA 55-year-old male presented with persistent aggravation of icteric sclera and skin. He was initially diagnosed with hilar cholangiocarcinoma and underwent surgery. However, positive IgG4 plasma cells were found in the surgical specimens. Thus, a pathological diagnosis of IgG4-SC was established. After that, steroid therapy was given and initially effective. But he was steroid dependent, and then received rituximab therapy twice. Unfortunately, the response to rituximab therapy was poor.ConclusionIt is crucial to differentiate isolated IgG4-SC from hilar cholangiocarcinoma to avoid unnecessary surgery. Future studies should further explore effective treatment strategy in patients who do not respond to steroids therapy. It is also required to develop novel and accurate diagnostic approaches to avoid unnecessary surgical procedures.

Parkinson’s disease resultant in the degeneration of Dopaminergic neurons and accumulation of α-synuclein in the substantia nigra pars compacta. The synthetic therapeutics for Parkinson’s disease have moderate symptomatic benefits but cannot prevent or delay disease progression. In this study, nicotine was employed by using transgenic Caenorhabditis elegans Parkinson’s disease models to minimize the Parkinson’s disease symptoms. The results showed that the nicotine at 100, 150, and 200 μM doses reduced degeneration of Dopaminergic neurons caused by 6-hydroxydopamine (14, 33, and 40%), lowered the aggregative toxicity of α-synuclein by 53, 56, and 78%, respectively. The reduction in food-sensing behavioral disabilities of BZ555 was observed to be 18, 49, and 86%, respectively, with nicotine concentrations of 100 μM, 150 μM, and 200 μM. Additionally, nicotine was found to enhance Daf-16 nuclear translocation by 14, 31, and 49%, and dose-dependently increased SOD-3 expression by 10, 19, and 23%. In summary, the nicotine might a promising therapy option for Parkinson’s disease.

Cardiovascular diseases (CVD) are the leading cause of death worldwide, despite advances in understanding cardiovascular health. Significant barriers still exist in effectively preventing and managing these diseases. Vascular smooth muscle cells (VSMCs) are crucial for maintaining vascular integrity and can switch between contractile and synthetic functions in response to stimuli such as hypoxia and inflammation. These transformations play a pivotal role in the progression of cardiovascular diseases, facilitating vascular modifications and disease advancement. This article synthesizes the current understanding of the mechanisms and signaling pathways regulating VSMC phenotypic transitions, highlighting their potential as therapeutic targets in cardiovascular disease interventions.

IntroductionWith increased life expectancy in the Chinese population coupled with chronic disease the care needs of people at the end of life are attracting much attention. Home hospice care can help the dying older adult achieve comfort and maintain their dignity at home. However, dying at home means great responsibility and challenge for family caregivers, and there are many unmet needs. The study aimed to investigate the home hospice care needs of family caregivers of older adult people with chronic diseases at the end of life in China, and to analyze the influencing factors of home hospice care needs of caregivers.MethodsIn this cross-sectional study, from May to September 2023, 4 community health service centers were selected by stratified sampling from seven administrative districts in Jinzhou City, Liaoning Province, where home hospice care was piloted. Then 224 family caregivers were selected from the communities of seven community service centers by simple random sampling method. A general information questionnaire and the home hospice care needs questionnaire developed by our research group were used to investigate. Univariate analysis was used to compare the differences in the scores of different characteristics, and the factors with significant differences were selected for multivariate linear regression analysis to determine the final influencing factors.ResultsThe total score of hospice care needs of family caregivers was 121.61 ± 15.24, among which the end-of-life knowledge need dimension score was 24.04 ± 2.71, the highest score index was 80.13%, while the symptom control need score was 15.58 ± 3.39, the lowest score index was 62.32%. In addition, Caregivers with caregiving experience, dying older adult with longer disease duration, and dying older adult with higher levels of education were the factors influencing the total need for home hospice care among family caregivers, with a variance explained of 22.7%.DiscussionThe needs of family caregivers of the terminally ill older adult are high, and healthcare professionals should implement services to meet their multidimensional needs and improve the quality of care according to the factors affecting their needs.

A metasurface antenna with wide impedance bandwidth and wide 3 dB gain bandwidth is proposed to broadband wireless communications. The antenna consists of a metasurface with non-uniform cells and a single-aperture-coupling feeding structure. The evolution process is analyzed to elaborate the operating principle of the proposed antenna. By modifying the structure of a conventional metasurface antenna, multi-modes resonance can be achieved to wider the bandwidth. Furthermore, the gain is enhanced in whole impedance bandwidth via etching slots on the patches. Due to the three modes are excited simultaneously, a wide impedance bandwidth and 3 dB gain bandwidth is obtained. A prototype is simulated, analyzed and measured to validate the principle. The results demonstrate that a peak gain of 9.3 dBi is obtained. Moreover, a wide impedance bandwidth over 90% and a wide 3 dB gain bandwidth over 90% is achieved.

In this paper, we consider the existence of positive solutions for a system of fractional $ q $-difference equations with generalized $ p $-Laplacian operators. By using Guo-Krasnosel'skii fixed point theorem, we obtain some existence results of positive solutions for this system with two parameters under some different combinations of superlinearity and sublinearity of the nonlinear terms. In the end, we give two examples to illustrate our main results.

Abstract Leaf senescence is a crucial trait that has a significant impact on crop quality and yield. Previous studies have demonstrated that light is a key factor in modulating the senescence process. However, the precise mechanism by which plants sense light and control senescence remains largely unknown, particularly in crop species. In this study, we reveal that the reduction in blue light under shading conditions can efficiently induce leaf senescence in soybean. The blue light receptors GmCRY1s rather than GmCRY2s, primarily regulate leaf senescence in response to blue light signals. Our results show that GmCRY1s interact with DELLA proteins under light-activated conditions, stabilizing them and consequently suppressing the transcription of GmWRKY100 to delay senescence. Conversely, LBL reduces the interaction between GmCRY1s and the DELLA proteins, leading to their degradation and premature senescence of leaves. Our findings suggest a GmCRY1s-GmDELLAs-GmWRKY100 regulatory cascade that is involved in mediating LBL-induced leaf senescence in soybean, providing insight into the mechanism of how light signals regulate leaf senescence. Additionally, we generate GmWRKY100 knockout soybeans that show delayed leaf senescence and improved yield under natural field conditions, indicating potential applications in enhancing soybean production by manipulating the leaf senescence trait.

Abstract Objective The purpose of this study was to translate the Awareness of Rights Scale into Chinese and test its psychometric properties among nursing students in clinical practice. Methods The original English scale was translated, synthesized, and back-translated according to the Brislin translation model: the translated scale was cross-culturally adapted through expert correspondence and pretesting to form the Chinese version of the scale; a convenience sampling method was used to survey 486 nursing interns in Liaoning, Guangdong, and Anhui regions to assess the reliability and validity of the scale. Results The Chinese version of the scale consists of 14 items in three dimensions. The Cronbach’s alpha value of the scale was 0.916 and the range of Cronbach’s alpha coefficients of subscale was 0.768 to 0.894. The discounted half reliability was 0.867 and the retest reliability was 0.901. The scale content validity index (S-CVI) was 0.963. A total of three common factors were extracted for the exploratory factor analysis. The confirmatory factor analysis indices fit well (χ2/df = 1.092, RMSEA = 0.014, CFI = 0.998, IFI = 0.998. TLI = 0.997), and the model fit was good. Conclusion The Chinese version of the scale has good reliability and validity in the nursing intern population and can be used to assess nursing interns’ awareness of their rights in clinical practice in mainland China.

Calotes wangi sp. nov., a new species of the agamid genus Calotes Cuvier, 1817, from southern China and northern Vietnam, is described. This species can be distinguished from all known congeners by a combination of morphological characteristics and genetic divergence in the mitochondrial tRNA, ND2, and CO1 genes. Molecular phylogenetic analysis revealed that the new species was formed as a monophyletic group and that considerable genetic divergence existed between its congeners (minimum p-distance, 4.6%). Calotes wangi sp. nov. is distinguished by a combination of the following characteristics: average SVL < 90 mm for adult males; 10–14 dorsal eyelid scales; scales on side of neck and adjacent shoulder area pointing obliquely upward; keels on neck scales weakly to strongly developed; fold in front of the shoulder absent; pair of dark triangular patches extending from the front of the shoulder to the jaw angles; and orange coloration of the tongue. Calotes wangi sp. nov. is similar to C. irawadi but differs in having scales between the nasal shield and the orbit and a fourth toe with a claw that can reach between the eyes and tympanum (even to the snout when hind the limbs are adpressed forward). Phylogenetic analyses revealed two well-supported subspecies, Lineages A and B in C. wangi sp. nov., with mean uncorrected p-distances between them of 2%. We propose that Lineage A, which is mainly from the central and southern Wuzhi Mountains on Hainan Island, is a subspecies, C. w. hainanensis ssp. nov. Lineage B mainly comprises individuals from other sites on the island plus the adjacent mainland, and is described as subspecies, C. w. wangi ssp. nov. A diagnostic key to all Calotes species of China is also provided.

Abstract Schistosomiasis, the second largest parasitic disease in the world after malaria, poses a significant threat to human health and causes public health issues. The disease primarily affects populations in economically underdeveloped tropical regions, earning it the title of “neglected tropical disease”. Schistosomiasis is difficult to eradicate globally if medication alone is used. One of the essential elements of thorough schistosomiasis prevention and control is the management and disruption of the life cycle of intermediate host snails. The key approach to controlling the transmission of schistosomiasis is to control the intermediate hosts of the schistosome to disrupt its life cycle. We believe that approaching it from the perspective of the intermediate host’s immunity could be an environmentally friendly and potentially effective method. Currently, globally significant intermediate host snails for schistosomes include Oncomelania hupensis, Biomphalaria glabrata, and Bulinus truncatus. The immune interaction research between B. glabrata and Schistosoma mansoni has a history of several decades, and the complete genome sequencing of both B. glabrata and B. truncatus has been accomplished. We have summarized the immune-related factors and research progress primarily studied in B. glabrata and B. truncatus and compared them with several humoral immune factors that O. hupensis research focuses on: macrophage migration inhibitory factor (MIF), Toll-like receptors (TLRs), and thioredoxin (Trx). We believe that continued exploration of the immune interactions between O. hupensis and Schistosoma japonicum is valuable. This comparative analysis can provide some direction and clues for further in-depth research. Comparative immunological studies between them not only expand our understanding of the immune defense responses of snails that act as intermediaries for schistosomes but also facilitate the development of more comprehensive and integrated strategies for schistosomiasis prevention and control. Furthermore, it offers an excellent opportunity to study the immune system of gastropods and their co-evolution with pathogenic organisms. Graphical Abstract

Abstract State‐of‐health (SOH) estimation methods for Li‐ion batteries are important for the safe operation of the entire system. However, it is often challenging due to the uncertainty within the batteries and the criteria for model interpretability. Belief rule base (BRB) is a rule‐based expert system that has certain advantages for both aspects. However, several problems with BRB interpretability need to be solved urgently. First, expert knowledge credibility is often given subjectively, while objective information is neglected to be considered. Second, BRB interpretability is easily ignored or corrupted in the optimization process. Third, expert knowledge is assumed to be completely reliable information to be used as interpretability evaluation criterion. Therefore, a new SOH estimation method for Li‐ion batteries based on interpretable BRB with expert knowledge credibility (IBRB‐c) is proposed. In the IBRB‐c, the calculation method of expert knowledge credibility is given. Then, an optimization algorithm with interpretability strategies is used. Finally, the concept of the fuzzy interpretable interval is proposed to design the interpretable evaluation criterion. The effectiveness of the proposed method is verified by using the experiment of NASA Li‐ion battery as a case study.

Using quinoa and oat bran as the primary raw materials, this study applied extrusion technology to create a quinoa compound powder, and the nutritional evaluation of the powder was carried out. A one-factor test was used to establish the process parameters. The optimal production process for quinoa blended powder was determined using an orthogonal test with the following parameters: 18% material moisture content, 130℃ extrusion temperature, 280 r/min screw speed, and 20 kg/h feeding speed. The compound powder produced under these conditions had a pleasant flavor and blended well, earning a sensory score of 92.5. The quality of quinoa flour was determined utilizing the nutritional quality index. The results indicated that the ratio of macronutrients to energy supply in quinoa flour was reasonable. Besides calcium, six mineral elements and four vitamins had INQ values greater than 1. With an AI value of 0.1489 and a TI value of 0.243, quinoa compound flour's fatty acids ratio was reasonable and rich in unsaturated fatty acids. Thus, quinoa compound powder is a high-protein, high-dietary-fiber, nutritionally-balanced food.

Abstract Phase separation, a biophysical segregation of subcellular milieus referred as condensates, is known to regulate transcription, but its impacts on physiological processes are less clear. Here, we demonstrate the formation of liquid-like nuclear condensates by SGF29, a component of the SAGA transcriptional coactivator complex, during cellular senescence in human mesenchymal progenitor cells (hMPCs) and fibroblasts. The Arg 207 within the intrinsically disordered region is identified as the key amino acid residue for SGF29 to form phase separation. Through epigenomic and transcriptomic analysis, our data indicated that both condensate formation and H3K4me3 binding of SGF29 are essential for establishing its precise chromatin location, recruiting transcriptional factors and co-activators to target specific genomic loci, and initiating the expression of genes associated with senescence, such as CDKN1A. The formation of SGF29 condensates alone, however, may not be sufficient to drive H3K4me3 binding or achieve transactivation functions. Our study establishes a link between phase separation and aging regulation, highlighting nuclear condensates as a functional unit that facilitate shaping transcriptional landscapes in aging.

A light source project named very compact inverse Compton scattering gamma-ray source (VIGAS) is under development at Tsinghua University. VIGAS aims to generate monochromatic high-energy gamma rays by colliding 350-MeV electron beams with 400-nm laser photons within a 12-m beamline. To produce a high-energy electron beam in such a compact space, the system consists of an S-band high-brightness injector and six X-band high-gradient accelerating structures. The goal of the X-band structure is to operate at a high gradient of 80 MV/m. Therefore, we adopts the constant gradient traveling wave approach, where the iris from the first cell to the end cell is tapered. The structure has 72 cells, including 70 cells and 2 couplers, so we named it XT72. The frequency of XT72 is selected to 11.424 GHz, and the 2π/3 mode is adopted. In this paper, we present a comprehensive study covering the detailed design, fabrication, rf tuning, and high-power test results of the first XT72. Additionally, we compare the performance of this structure to that of the previous constant impedance structure. Our results demonstrate that the XT72 is capable of operating at an 80-MV/m gradient with a lower breakdown rate. This advancement paves the way for the development of VIGAS project and contributes to the wider application of X-band room-temperature high-gradient structures in compact accelerator facilities.

With the increasing acquisition speed of image sensors, it has become necessary to provide image sources with higher frame rates and grayscale in order to meet testing requirements. In the field of semi-physical simulation projection, digital micromirror devices are often chosen for their high resolution, uniformity, response speed, and energy concentration. In this study, we utilized digital micromirror devices to construct a high-frame-rate and large-grayscale simulation projection system. To achieve our experiment goals, we employed two digital micromirror devices. One DMD was used to modulate the light intensity of the light source, while the other generated images with different bit planes. By projecting the target images onto the image sensor, we were able to achieve a frame rate of 1611 hz for the projected 12-bit image. This system meets the requirements for our experiment design and ensures the accurate testing of image sensors.

Puccinia graminis f. sp. tritici (Pgt), the causal agent of wheat stem rust, poses a significant threat to global wheat production. Genetic resistance offers a cost-effective and sustainable solution. The durum wheat landrace PI 94701 was previously hypothesized to carry two stem rust resistance (Sr) genes, but their chromosomal locations were unknown. In this study, we mapped and characterized an all-stage Sr gene in PI 94701, temporarily designated as SrPI94701. In seedling tests, SrPI94701 was effective against all six Pgt races tested. Using a large segregating population, we mapped SrPI94701 on chromosome arm 5BL within a 0.17-cM region flanked by markers pku69124 and pku69228, corresponding to 1.04 and 2.15 Mb genomic regions in the Svevo and Chinese Spring reference genomes. Within the candidate region, eight genes exhibited differential expression between the Pgt-inoculated resistant and susceptible plants. Among them, two nucleotide-binding leucine-rich repeat (NLR) genes, TraesCS5B03G1334700 and TraesCS5B03G1335100, showed high polymorphism between the parental lines and were upregulated in Pgt-inoculated resistant plants. However, the flanking and completely linked markers developed in this study could not accurately predict the presence of SrPI94701 in a survey of 104 wheat accessions. SrPI94701 is a promising resource for enhancing stem rust resistance in wheat breeding programs.

Abstract Optoelectronic logic gates have emerged as one of the key candidates for the creation of next generation logic devices. However, current optoelectronic logic gates can provide only one or two logic gates, severely limiting their applications. Here we report a self‐powered and mechanically flexible device based on a BaTiO3 ferroelectric film to produce multi‐modal logic gates. By exploiting the photo‐induced photovoltaic and pyroelectric effects of a Schottky junction which is created between BaTiO3 and LaNiO3, the device is able to provide five different optoelectronic logic gates, which can be operated using input lasers of different wavelength (405 or 785 nm). The mode of operation of the logic gate can be switched by controlling the wavelength and intensity of the input laser, where the switching process is both lossless and reversible. A logic gate array was designed to conduct the five logic operations, with 100% accuracy, thereby providing application potential for the Internet of Things, big data, and secure solutions for data processing and transmission.

IntroductionActivation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE), C57BL/6 mice develop mild kidney damage in association with glomerular IgA deposition. To further address complement activity in causing glomerular histological alterations as suggested in the pathogenesis of IgAN, here we used mice with factor H mutation (FHW/R) to render AP overactivation in conjunction with LCWE injection to stimulate intestinal production of IgA.MethodsDose response to LCWE were examined between two groups of FHW/R mice. Wild type (FHW/W) mice stimulated with LCWE were used as model control.ResultsThe FHW/R mice primed with high dose LCWE showed elevated IgA and IgA-IgG complex levels in serum. In addition to 100% positive rate of IgA and C3, they display elevated biomarkers of kidney dysfunction, coincided with severe pathological lesions, resembling those of IgAN. As compared to wild type controls stimulated by the same high dose LCWE, these FHW/R mice exhibited stronger complement activation in the kidney and in circulation.DiscussionThe new mouse model shares many disease features with IgAN. The severity of glomerular lesions and the decline of kidney functions are further aggravated through complement overactivation. The model may be a useful tool for preclinical evaluation of treatment response to complement-inhibitors.

Background: The potential effects of short-term exposure to major ambient gaseous pollutants (ozone: O3, carbon monoxide: CO, and sulfur dioxide: SO2) on platelet mitochondrial DNA (mtDNA) methylation have been uncertain and no studies have examined whether platelet mtDNA methylation levels could modify the associations between ambient gaseous pollutants and the risks of ST-segment depression (STDE) and T-wave inversion events (TIE), two indicators of myocardial ischemia. Methods: This study used data from a randomized, double-blind, placebo-controlled intervention study with a standardized 24-hour exposure protocol among 110 participants in Beijing. Absolute changes in platelet mtDNA methylation (ACmtDNAm) levels were determined by two repeated measurements on platelet mtDNA methylation levels in blood samples collected before and after the 24-hour exposure period. A multivariable linear regression model and a generalized linear model with a Poisson link function were used to investigate the associations of ambient gaseous pollutants with platelet mtDNA methylation levels, STDE, and TIE, respectively. Results: Short-term O3 exposure was significantly associated with decreased ACmtDNAm at ATP6_P1 but increased ACmtDNAm at mt12sRNA, MT-COX1, and MT-COX1_P2; short-term CO and SO2 exposures were significantly associated with decreased ACmtDNAm at D-loop, MT-COX3- and ATP-related genes. Moreover, short-term O3 exposure was significantly associated with increased risks of STDE and TIE, and ACmtDNAm at MT-COX1 and MT-COX1_P2 modified the association between short-term O3 exposure and STDE events. L-Arg supplementation attenuated the effects of ambient gaseous pollutants, particularly O3, on ACmtDNAm and STDE. Conclusions: Platelet mtDNA methylation levels are promising biomarkers of short-term exposure to ambient gaseous air pollution, and are likely implicated in the mechanism behind the association of ambient O3 pollution with adverse cardiovascular effects. L-Arg supplementation showed the potential to mitigate the adverse effects of ambient O3 pollution.

Abstract Background Numerous of models have been developed to predict the bone metastasis (BM) risk; however, due to the variety of cancer types, it is difficult for clinicians to use these models efficiently. We aimed to perform the pan‐cancer analysis to create the cancer classification system for BM, and construct the nomogram for predicting the BM risk. Methods Cancer patients diagnosed between 2010 and 2018 in the Surveillance, Epidemiology, and End Results (SEER) database were included. Unsupervised hierarchical clustering analysis was performed to create the BM prevalence‐based cancer classification system (BM‐CCS). Multivariable logistic regression was applied to investigate the possible associated factors for BM and construct a nomogram for BM risk prediction. The patients diagnosed between 2017 and 2018 were selected for validating the performance of the BM‐CCS and the nomogram, respectively. Results A total of 50 cancer types with 2,438,680 patients were included in the construction model. Unsupervised hierarchical clustering analysis classified the 50 cancer types into three main phenotypes, namely, categories A, B, and C. The pooled BM prevalence in category A (17.7%; 95% CI: 17.5%–17.8%) was significantly higher than that in category B (5.0%; 95% CI: 4.5%–5.6%), and category C (1.2%; 95% CI: 1.1%–1.4%) (p

Gastric cancer (GC) remains one of the most life-threatening disease worldwide with poor prognosis because of the absence of effective treatment and the delay in diagnosis. Due to the delay of diagnosis, a large proportion of GC patients are diagnosed as advanced GC, with extreme short lifespan. In the past few years, some pivotal progress and novel therapies was proposed, and conducted into clinical researches and practice. In this study, we summarized the development of several novel immunotherapy or targeted treatment modalities for advanced GC, including immune checkpoint inhibitors, anti-angiogenic therapy and cancer vaccines. Additionally, the advantage and potential weakness in each of these therapeutic methods are also listed. Finally, we discussed the promising research direction of advanced GC treatment, and the limitation in basic and clinical research of advanced GC, including the combination of immunotherapy and targeted therapy.

Abstract Shading in combination with extended photoperiods can cause exaggerated stem elongation (ESE) in soybean, leading to lodging and reduced yields when planted at high-density in high-latitude regions. However, the genetic basis of plant height in adaptation to these regions remains unclear. Here, through a genome-wide association study, we identify a plant height regulating gene on chromosome 13 (PH13) encoding a WD40 protein with three main haplotypes in natural populations. We find that an insertion of a Ty1/Copia-like retrotransposon in the haplotype 3 leads to a truncated PH13H3 with reduced interaction with GmCOP1s, resulting in accumulation of STF1/2, and reduced plant height. In addition, PH13 H3 allele has been strongly selected for genetic improvement at high latitudes. Deletion of both PH13 and its paralogue PHP can prevent shade-induced ESE and allow high-density planting. This study provides insights into the mechanism of shade-resistance and offers potential solutions for breeding high-yielding soybean cultivar for high-latitude regions.

Abstract Background In recent years, the development of BMSCs-derived exosomes (EXO) for the treatment of osteosarcoma (OS) is a safe and promising modality for OS treatment, which can effectively deliver drugs to tumor cells in vivo. However, the differences in the drugs carried, and the binding of EXOs to other organs limit their therapeutic efficacy. Therefore, improving the OS-targeting ability of BMSCs EXOs and developing new drugs is crucial for the clinical application of targeted therapy for OS. Results In this study, we constructed a potential therapeutic nano platform by modifying BMSCs EXOs using the bone-targeting peptide SDSSD and encapsulated capreomycin (CAP) within a shell. These constructed nanoparticles (NPs) showed the ability of homologous targeting and bone-targeting exosomes (BT-EXO) significantly promotes cellular endocytosis in vitro and tumor accumulation in vivo. Furthermore, our results revealed that the constructed NPs induced ferroptosis in OS cells by prompting excessive accumulation of reactive oxygen species (ROS), Fe2+ aggregation, and lipid peroxidation and further identified the potential anticancer molecular mechanism of ferroptosis as transduced by the Keap1/Nrf2/GPX4 signaling pathway. Also, these constructed NP-directed ferroptosis showed significant inhibition of tumor growth in vivo with no significant side effects. Conclusion These results suggest that these constructed NPs have superior anticancer activity in mouse models of OS in vitro and in vivo, providing a new and promising strategy for combining ferroptosis-based chemotherapy with targeted therapy for OS.

Abstract Background No consensus currently exists regarding the optimal protocol for repetitive transcranial magnetic stimulation (rTMS) treatment of upper-extremity motor dysfunction after stroke. Studies have shown that combined low- and high-frequency stimulation (LF-HF-rTMS) of the bilateral cerebral hemispheres is more effective than sham stimulation or stimulation of one cerebral hemisphere alone in treating motor dysfunction in the subacute stage of stroke. The efficacy of this protocol in the convalescence phase of stroke has rarely been reported, and its mechanism of action has not been clarified. In this study, we designed a prospective, single-blind, randomized controlled trial to investigate the efficacy and safety of different stimulation regimens for the treatment of upper extremity motor disorders in patients with convalescent stage stroke and aimed to explore the underlying mechanisms based on biomarkers such as brain-derived neurotrophic factor (BDNF). Methods Seventy-six subjects will be randomly divided into combined, low-frequency, high-frequency, and control groups based on the proportion of 1:1:1:1, with 19 cases in each group. All groups will have conventional rehabilitation, on top of which the combined group will receive 1 Hz rTMS in the unaffected hemisphere and 10 Hz rTMS in the affected hemisphere. The low-frequency group will be administered 1 Hz rTMS in the unaffected hemisphere and sham stimulation in the contralateral hemisphere. The high-frequency group will be administered 10 Hz rTMS in the affected hemisphere and contralateral sham stimulation. The control group will receive bilateral sham stimulation. Assessments will be performed at baseline, after 2 weeks of treatment, and at post-treatment follow-up at week 6. The primary outcomes are FMA-UE (Fugl-Meyer assessment-upper extremity), latency, and serum BDNF levels. The secondary outcomes are the National Institute of Health Stroke Scale (NIHSS), Brunnstrom staging (BS), modified Ashworth scale (MAS), Modified Barthel Index (MBI), central motor conduction time (CMCT), precursor proteins of mature BDNF (proBDNF), and matrix metalloproteinase-9 (MMP-9) levels. Adverse events, such as headaches and seizures, will be recorded throughout the study. Discussion The findings of this study will help develop optimal stimulation protocols for motor recovery in stroke patients and identify biomarkers that respond to post-stroke motor rehabilitation, for better guidance of clinical treatment. Trial registration The study protocol was passed by the Medical Research Ethics Committee of the General Hospital of Ningxia Medical University on January 1, 2022 (no. KYLL-2021–1082). It was registered into the Chinese Clinical Trials Registry on May 22, 2022 (no. ChiCTR2200060201). This study is currently in progress. Graphical Abstract