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Highlights The lithium-ion conduction mechanism of organic-inorganic composite solid electrolytes (OICSEs) is thoroughly conducted and concluded from the microscopic perspective based on filler content, type, and system. The classic inorganic filler types, including inert and active fillers, are categorized with special emphasis on the relationship between inorganic filler structure design and the electrochemical performance of OICSEs. Advanced characterization techniques for OICSEs are discussed, and the challenges and prospects for developing superior all-solid-state lithium batteries are highlighted.

Abstract The various mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose a substantial challenge in mitigating the viral infectivity. The identification of novel host factors influencing SARS-CoV-2 replication holds potential for discovering new targets for broad-spectrum antiviral drugs that can combat future viral mutations. In this study, potential host factors regulated by SARS-CoV-2 infection were screened through different high-throughput sequencing techniques and further identified in cells. Subsequent analysis and experiments showed that the reduction of m6A modification level on ACTN4 (Alpha-actinin-4) mRNA leads to a decrease in mRNA stability and translation efficiency, ultimately inhibiting ACTN4 expression. In addition, ACTN4 was demonstrated to target nsp12 for binding and characterized as a competitor for SARS-CoV-2 RNA and the RNA-dependent RNA polymerase complex, thereby impeding viral replication. Furthermore, two ACTN4 agonists, YS-49 and demethyl-coclaurine, were found to dose-dependently inhibit SARS-CoV-2 infection in both Huh7 cells and K18-hACE2 transgenic mice. Collectively, this study unveils the pivotal role of ACTN4 in SARS-CoV-2 infection, offering novel insights into the intricate interplay between the virus and host cells, and reveals two potential candidates for future anti-SARS-CoV-2 drug development.

Abstract Background Magnetic resonance spectroscopy (MRS) studies have indicated that the imbalance between gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels was the potential cause of migraine development. However, the changes in the GABA and Glx levels in patients with New daily persistent headache (NDPH) remain unclear. This study aimed to investigate the changes in GABA and Glx levels in the periaqueductal gray (PAG) and dentate nucleus (DN) in patients with NDPH using the MEGA-PRESS sequence. Methods Twenty-one NDPH patients and 22 age- and sex-matched healthy controls (HCs) were included and underwent a 3.0T MRI examination, using the MEGA-PRESS sequence to analyze GABA and Glx levels of PAG and DN. The correlations between these neurotransmitter levels and clinical characteristics were also analyzed. Results There were no significant differences in the GABA+/Water, GABA+/Cr, Glx/Water, and Glx/Cr levels in both PAG and DN between the two groups (all p > 0.05). Moderate-severe NDPH patients had lower levels of Glx/Water (p = 0.034) and Glx/Cr (p = 0.012) in DN than minimal-mild NDPH patients. In patients with NDPH, higher Glx/Water levels in the PAG (r=-0.471, p = 0.031, n = 21) and DN (r=-0.501, p = 0.021, n = 21) and higher Glx/Cr levels in DN (r=-0.483, p = 0.026, n = 21) were found to be correlated with lower Visual Analogue Scale scores. Additionally, a positive correlation was observed between the GABA+/Cr levels in the DN and the Generalized Anxiety Disorder-7 scores (r = 0.519, p = 0.039, n = 16). Conclusions The results of this study indicated that the GABA and Glx levels in the PAG and DN may not be the primary contributor to the development of NDPH. The correlations between certain clinical scales and the neurotransmitter levels may be derived from the NDPH related symptoms.

Abstract Background Work-related musculoskeletal disorders (WMSDs) show a rapid growth trend. It has brought a huge economic burden to the society and become a serious occupational health problem that needs to be solved urgently. This study aimed to analyze the local muscle response under continuous ergonomic load, screen sensitive fatigue-related biomarkers and provide data support for the early prevention of local muscle damage and the exploration of early warning indicators. Methods Thirteen male college student volunteers were recruited to perform simulated repetitive manual lifting tasks in the laboratory. The lifting task was designed for 4 periods which lasted for 12 min in each, and then paused for 3 min for sampling. Local muscle fatigue is assesed by the Rating of perceived exertion (RPE) and the Joint analysis of sEMG spectrum and amplitude (JASA). Elbow venous blood was collected and 14 kinds of biomarkers were analyzed, which included Metabolic markers Ammonia (AMM), Lactic acid (LAC), Creatine kinase (CK), Lactate dehydrogenase (LDH), Cartilage oligomeric matrix protein (COMP), C-telopeptide of collagen I and II (CTX-I, CTX-II) and Calcium ion (Ca2+); Oxidative stress marker Glutathione (GSH); Inflammatory markers C-reaction protein (CRP), Prostaglandin E2 (PG-E2), Interleukin-6 (IL-6) and Tumor necrosis factor α (TNF-α); Pain marker Neuropeptide Y (NPY). Repeated measures analysis of variance (Repeated ANOVA), linear regression analysis, t-test and spearman correlation analysis were used to analyze the data. Results Both subjective and objective fatigue appeared at the same period. Serum AMM, LAC, CK, LDH, COMP, CTX-II, Ca2+ and NPY after fatigue were significantly higher than those before fatigue (p

Abstract Background Soybean mosaic disease caused by soybean mosaic virus (SMV) is one of the most devastating and widespread diseases in soybean producing areas worldwide. The WRKY transcription factors (TFs) are widely involved in plant development and stress responses. However, the roles of the GmWRKY TFs in resistance to SMV are largely unclear. Results Here, 185 GmWRKYs were characterized in soybean (Glycine max), among which 60 GmWRKY genes were differentially expressed during SMV infection according to the transcriptome data. The transcriptome data and RT-qPCR results showed that the expression of GmWRKY164 decreased after imidazole treatment and had higher expression levels in the incompatible combination between soybean cultivar variety Jidou 7 and SMV strain N3. Remarkably, the silencing of GmWRKY164 reduced callose deposition and enhanced virus spread during SMV infection. In addition, the transcript levels of the GmGSL7c were dramatically lower upon the silencing of GmWRKY164. Furthermore, EMSA and ChIP-qPCR revealed that GmWRKY164 can directly bind to the promoter of GmGSL7c, which contains the W-box element. Conclusion Our findings suggest that GmWRKY164 plays a positive role in resistance to SMV infection by regulating the expression of GmGSL7c, resulting in the deposition of callose and the inhibition of viral movement, which provides guidance for future studies in understanding virus-resistance mechanisms in soybean.

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

BackgroundChemotherapy combined with PD-1 inhibitor treatment has revolutionized the standard of care for patients with NSCLC. However, the benefit is not universal, highlighting the need for precise prediction factors. Given their relationship with the immune system and non-invasive nature, serum cytokines are potential candidates for predicting the clinical effects of chemoimmunotherapy. Our study aims to evaluate the association of serum cytokines with the prognosis of patients with NSCLC treated with chemoimmunotherapy.MethodsLevels of 10 serum cytokines were detected in 60 NSCLC patients receiving chemotherapy plus PD-1 inhibitor-based treatment. Of these, dynamic samples from 19 patients were collected at baseline and after two treatment cycles. Their association with patients’ clinicopathological characteristics, PFS and OS was described and investigated using survival analysis, cox regression and time-dependent ROC analysis. Preliminary evaluation of changes in cytokine levels associated with treatment response was conducted.ResultsPatients with lower baseline levels of serum IL-6, IL-5, IL-8, TNF-α and IL-10 had longer PFS, while patients with higher levels of IL-4 had longer PFS. Patients with lower levels of serum IL-6, IL-8, IL-22, TNF-α and IL-10 had longer OS, while patients with higher levels of IL-4 had longer OS. Multivariate analysis suggested that higher IL-6 and IL-5 levels were associated with poorer PFS, and higher IL-6 levels were associated with dismal OS. Additionally, changes in serum cytokine levels could be associated with treatment response.ConclusionOur study suggests that serum cytokines, specifically IL-6, IL-5, IL-8, TNF-α, IL-10, and IL-4, are potential prognostic factors for patients with NSCLC receiving chemotherapy plus PD-1 inhibitor treatment.

Abstract Background The 9th edition of the TNM Classification for lung cancer delineates M1c into two subcategories: M1c1 (Multiple extrathoracic lesions within a single organ system) and M1c2 (Multiple extrathoracic lesions involving multiple organ systems). Existing research indicates that patients with lung cancer in stage M1c1 exhibit superior overall survival compared to those in stage M1c2. The primary frontline therapy for patients with advanced non‐small cell lung cancer (NSCLC), lacking driver gene mutations, involves the use of immune checkpoint inhibitors (ICIs) combined with chemotherapy. Nevertheless, a dearth of evidence exists regarding potential survival disparities between NSCLC patients with M1c1 and M1c2 undergoing first‐line immune‐chemotherapy, and reliable biomarkers for predicting treatment outcomes are elusive. Serum metabolic profiles may elucidate distinct prognostic mechanisms, necessitating the identification of divergent metabolites in M1c1 and M1c2 undergoing combination therapy. This study seeks to scrutinize survival discrepancies between various metastatic patterns (M1c1 and M1c2) and pinpoint metabolites associated with treatment outcomes in NSCLC patients undergoing first‐line ICIs combined with chemotherapy. Method In this study, 33 NSCLC patients lacking driver gene mutations diagnosed with M1c1, and 22 similarly diagnosed with M1c2 according to the 9th edition of TNM Classification, were enrolled. These patients received first‐line PD‐1 inhibitor plus chemotherapy. The relationship between metastatic patterns and progression‐free survival (PFS) in patients undergoing combination therapy was analyzed using univariate and multivariate Cox regression models. Serum samples were obtained from all patients before treatment initiation for untargeted metabolomics analysis, aiming to identify differential metabolites. Results In the univariate analysis of PFS, NSCLC patients in M1c1 receiving first‐line PD‐1 inhibitor plus chemotherapy exhibited an extended PFS (HR = 0.49, 95% CI, 0.27–0.88, p = 0.017). In multivariate PFS analyses, these M1c1 patients receiving first‐line PD‐1 inhibitor plus chemotherapy also demonstrated prolonged PFS (HR = 0.45, 95% CI, 0.22–0.92, p = 0.028). The serum metabolic profiles of M1c1 and M1c2 undergoing first‐line PD‐1 inhibitors plus chemotherapy displayed notable distinctions. In comparison to M1c1 patients, M1c2 patients exhibited alterations in various pathways pretreatment, including platelet activation, linoleic acid metabolism, and the VEGF signaling pathway. Diminished levels of lipid‐associated metabolites (diacylglycerol, sphingomyelin) were correlated with adverse outcomes. Conclusion NSCLC patients in M1c1, devoid of driver gene mutations, receiving first‐line PD‐1 inhibitors combined with chemotherapy, experienced superior outcomes compared to M1c2 patients. Moreover, metabolomic profiles strongly correlated with the prognosis of these patients, and M1c2 patients with unfavorable outcomes manifested distinct changes in metabolic pathways before treatment. These changes predominantly involved alterations in lipid metabolism, such as decreased diacylglycerol and sphingomyelin, which may impact tumor migration and invasion.

The L-type Ca2+ channel (LTCC, also known as Cav1,2) is involved in the regulation of key neuronal functions, such as dendritic information integration, cell survival, and neuronal gene expression. Clinical studies have shown an association between L-type calcium channels and the onset of depression, although the precise mechanisms remain unclear. The development of depression results from a combination of environmental and genetic factors. DNA methylation, a significant epigenetic modification, plays a regulatory role in the pathogenesis of psychiatric disorders such as posttraumatic stress disorder (PTSD), depression, and autism. In our study, we observed reduced Dnmt3a expression levels in the hippocampal DG region of mice with LPS-induced depression compared to control mice. The antidepressant Venlafaxine was able to increase Dnmt3a expression levels. Conversely, Bay K 8644, an agonist of the L-type Ca2+ channel, partially ameliorated depression-like behaviors but did not elevate Dnmt3a expression levels. Furthermore, when we manipulated DNA methylation levels during Bay K 8644 intervention in depression-like models, we found that enhancing the expression of Dnmt3a could improve LPS-induced depression/anxiety-like behaviors, while inhibiting DNA methylation exacerbated anxiety-like behaviors, the combined use of BAY K 8644 and L-methionine can better improve depressive-like behavior. These findings indicate that DNA methylation plays a role in the regulation of depression-like behaviors by the L-type Ca2+ channel, and further research is needed to elucidate the interactions between DNA methylation and L-type Ca2+ channels.

BackgroundObservational studies have suggested at a possible link between keratoconus (KC) and various mental disorders, but the exact direction of causation in these associations remains unclear. This study aims to investigate the potential causal link between KC and three prominent mental conditions: Anxiety, Depression, and Schizophrenia.MethodsUsing instrumental variables identified from Genome-wide association study (GWAS) data of European individuals, we conducted bidirectional two-sample Mendelian Randomization (MR) analyses to explore potential causal relationships between KC and the three major mental disorders. We primarily employed the Inverse-Variance Weighted (IVW) method to evaluate causality. In addition, we performed four supplementary MR methods (MR-Egger, Weighted Median, Simple Mode, and Weighted Mode). Furthermore, we conducted various sensitivity analyses to assess heterogeneity, horizontal pleiotropy, and result stability.ResultsOur findings did not reveal any concrete evidence of a causal link between KC and the three major mental disorders, namely anxiety, depression, and schizophrenia [anxiety: odds ratio (OR)=0.997, 95% confidence interval (CI)=0.988–1.008, p = 0.621; depression: OR=1.008, 95% CI=0.999–1.017, p = 0.084; schizophrenia: OR=1.002, 95% CI= 0.984–1.020, p = 0.840]. Similarly, the three major mental disorders were not caustically associated with KC [anxiety: OR=1.014, 95% CI=0.635–1.620, p = 0.953; depression: OR=1.109, 95% CI= 0.749–1.643, p = 0.604; schizophrenia: OR= 0.969, 95% CI= 0.884–1.062, p = 0.497]. The sensitivity analyses indicated that the results remained robust, with no signs of pleiotropy or heterogeneity.ConclusionsOur study does not support a genetically determined significant causal connection between KC and the three major mental disorders. The increased occurrence of mental disorders observed in KC patients in observational reports likely arises from factors that can be modified. Further research is warranted to unveil the underlying mechanisms behind the associations observed in observational studies.

Endometriosis is an estrogen-dependent inflammatory gynecological disease whose pathogenesis is unclear. C-C motif chemokine ligand 18 (CCL18), a chemokine, is involved in several inflammatory diseases. In this study, we aimed to investigate the role of CCL18 in endometriosis and its underlying mechanisms. Human endometrium and peritoneal fluid were obtained from women with and without endometriosis for molecular studies. The expression level of CCL18 in each tissue sample was examined by RNA sequencing analysis, quantitative PCR analysis and immunohistochemistry staining. The effects of CCL18 on cell migration, tube formation and neurite growth were investigated in vitro using primary endometrial cells, human umbilical vein endothelial cells (HUVECs) and dorsal root ganglion (DRG) neurons, respectively. Moreover, the development of endometriosis in mice was studied in vivo by blocking CCL18. CCL18 was shown to be overexpressed in endometrial foci and peritoneal fluid in women with endometriosis and was positively correlated with endometriosis pain. In vitro, CCL18 promoted the migration of ectopic endometrial cells, tube formation of HUVECs, and nerve outgrowth of DRG neurons. More importantly, inhibition of CCL18 significantly suppressed lesion development, angiogenesis, and nerve infiltration in a mouse model of endometriosis. In conclusion, CCL18 may play a role in the progression of endometriosis by increasing endometrial cell migration and promoting neuroangiogenesis.

Abstract Female and latent genital tuberculosis (FGTB and LGTB) in young women may lead to infertility by damaging ovarian reserve function, but the regulatory mechanisms remain unclear. In this study, we investigated the effects of FGTB and LGTB on ovarian reserve function and potential regulatory mechanisms by untargeted metabolomics of follicular fluid, aiming to provide insights for the clinical management and treatment approaches for afflicted women. We recruited 19 patients with FGTB, 16 patients with LGTB, and 16 healthy women as a control group. Clinical data analysis revealed that both the FGTB and LGTB groups had significantly lower ovarian reserve marker levels compared to the control group, including lower anti-Müllerian hormone levels (FGTB: 0.82 [0.6, 1.1] μg/L; LGTB: 1.57 [1.3, 1.8] μg/L vs. control: 3.29 [2.9, 3.5] μg/L), reduced antral follicular counts (FGTB: 6 [5.5, 9.5]; LGTB: 10.5 [7, 12.3] vs. control: 17 [14.5, 18]), and fewer retrieved oocytes (FGTB: 3 [2, 5]; LGTB: 8 [4, 8.3] vs. control: 14.5 [11.5, 15.3]). Conversely, these groups exhibited higher ovarian response marker levels, such as longer gonadotropin treatment days (FGTB: 12 [10.5, 12.5]; LGTB: 11 [10.8, 11.3] vs. control: 10 [8.8, 10]) and increased gonadotropin dosage requirements (FGTB: 3300 [3075, 3637.5] U; LGTB: 3037.5 [2700, 3225] U vs. control: 2531.25 [2337.5, 2943.8] U). All comparisons were statistically significant at P

Abstract Asthma is a common allergic disease characterized by airway hypersensitivity and airway remodeling. Ferroptosis is a regulated death marked by iron accumulation and lipid peroxidation. Several environmental pollutants and allergens have been shown to cause ferroptosis in epithelial cells, but the relationship between birch pollinosis and ferroptosis in asthma is poorly defined. Here, for the first time, we have identified ferroptosis of type II alveolar epithelial cells in mice with Bet v 1-induced asthma. Further analysis revealed that treatment with ferrostatin-1 reduced TH2/TH17-related inflammation and alleviated epithelial damage in mice with Bet v 1-induced asthma. In addition, ACSL4-knocked-down A549 cells are more resistant to Bet v 1-induced ferroptosis. Analysis of clinical samples verified higher serum MDA and 4-HNE concentrations compared to healthy individuals. We demonstrate that birch pollen allergen Bet v 1 induces ferroptosis underlaid TH2 and TH17 hybrid asthma. Lipid peroxidation levels can be considered as a biomarker of asthma severity, and treatment with a specific ferroptosis inhibitor could be a novel therapeutic strategy.

ABSTRACTConvex and concave hulls originating from computational geometry are widely applied in practice. For instance, to determine the boundaries of a geographical area within a group of cities, convex hulls can represent the approximate boundaries of the areas. Concave hulls can accurately describe the shape of the area. The traditional methods for solving two-dimensional convex hull problems include the Jarvis March algorithm and the Graham scanning algorithm. The K-nearest neighbours and alpha-shape methods are designed for solving the concave hull problem. Other than traditional algorithms, we consider using deep neural networks to handle the convex and concave hull problems. General neural networks cannot deal with the problem whose output is a variable-length sequence. Our study provides a machine-learning approach for solving the convex hull and concave hull problems. We combine the Pointer network (Ptr-Net) with the Transformer model and propose the DeepHullNet. The trained DeepHullNet can provide a feasible solution in the majority of cases. The experimental results show that DeepHullNet outperforms the original Ptr-Net regarding accuracy. Compared with traditional methods, DeepHullNet can generate a good solution quickly, and the running time is shortened by nearly 100 times based on GPU.

ABSTRACTUrban spatial decision analysis is a critical component of spatial optimization and has profound implications in various fields, such as urban planning, logistics distribution, and emergency management. Existing studies on urban facility location problems are based on heuristic methods. However, few studies have used deep learning to solve this problem. In this study, we introduce a unified framework, SpoNet. It combines the characteristics of location problems with a deep learning model SpoNet can solve spatial optimization problems: p-Median, p-Center, and maximum covering location problem (MCLP). It involves modeling each problem as a Markov Decision Process and using deep reinforcement learning to train the model. To improve the training efficiency and performance, we integrated knowledge SpoNet. The results demonstrated that the proposed method has several advantages. First, it can provide a feasible solution without the need for complex calculations. Second, integrating the knowledge model improved the overall performance of the model. Finally, SpoNet is more accurate than heuristic methods and significantly faster than modern solvers, with a solution time improvement of more than 20 times. Our method has a promising application in urban spatial decision analysis, and further has a positive impact on sustainable cities and communities.

Purslane is often labeled as a noxious weed in Florida; however, this seemingly pesky plant is perceived as a nutritional powerhouse in Asia and other continents. Levels of vitamin A and E in purslane far surpass those found in broccoli, tomato, and lettuce. A mere 3.5 ounces of purslane can fulfill 81% of an individual's daily vitamin requirements, and up to half a pound can meet the daily needs for both Vitamins A and E. Sustaining this nutritional wealth hinges on the timing of harvest when purslane plants attain a height of 5 to 6 inches. Beyond this stage, purslane becomes excessively fibrous and aged, making it unsuitable for consumption and necessitating removal through weeding. This publication article provides a comprehensive overview of purslane, delving into its botany, garden production, harvest practices, and both culinary and medicinal uses to assist growers and consumers in understanding when to savor its nutritional benefits and when to weed it from farmlands.

The complex network approach is an effective method to analyze the global properties of complex biological systems, which can be used to explore the interactions between multiple compounds and protein targets of drug. Radix Pueraria has a long history of efficacy in different diseases, containing a variety of compounds that can produce multiple therapeutic effects via multiple targets. To explore the interrelationship between compounds of Radix Pueraria, protein targets, and pathways, the present investigation used the complex network approach to construct the compound-protein target-pathway network of Radix Pueraria. The analysis of the statistical and topological characteristics shows that the network has small-world and scale-free characteristics. The diameter of the network is 7, indicating that the information exchange between two nodes could quickly spread to the whole network. With the rank of degree value and integrated centrality as identification indicators, by taking the threshold of integrated centrality as 0.70, a total of nine key hub nodes containing three active compounds, two protein targets, and four biological pathways were identified: genistein, daidzein, puerarin, MAPK3, MAPK1, hsa01100, hsa05200, hsa05417, and hsa05207. The network analysis suggests these key hub nodes should play an important role in the pharmacological action of Radix Pueraria. The results of this study provide useful information and knowledge for further exploring the pharmacological mechanism of Radix Pueraria in the course of disease treatment.

With global warming, the winter oilseed rape planting area in Northwest China is gradually increasing. It is vital to address the problems faced by winter oilseed rape cultivation in this region, such as low winter temperature, water shortage and low resources utilization efficiency. To explore the coupling effects of supplementary irrigation level and nitrogen (N) application rate on winter oilseed rape growth, water and N use efficiency, and determine the multi-objective optimal water-N management strategies, a two-year field experiment was conducted (2020–2021 and 2021–2022). The experiments included three supplementary irrigation levels (I0: rainfed; I1: supplementary irrigation at overwintering stage; I2: supplementary irrigation at overwintering and budding stages) and five N application rates (N0: 0 kg/hm2; N1: 120 kg/hm2; N2: 200 kg/hm2; N3: 280 kg/hm2; N4: 360 kg/hm2). The results showed that supplementary irrigation at overwintering and budding stages (I2) can improve the physiological growth indexes, N accumulation and utilization, main quality indexes, and yield of winter oilseed rape. Under I2, LAI, aboveground biomass, chlorophyll content, water use efficiency, N accumulation, N agronomy efficiency and yield of winter oilseed rape first increased and then decreased as N application rate increased, and all reached maximized at medium levels of N application rate (N2 or N3). Under the same irrigation level, the oil content of grain decreased as N application rate increased, while the protein and thioside acid content increased. Based on the TOPSIS with Nash equilibrium-combination weighting method, the multi-objective optimal strategies were determined to be the combination of supplementary irrigation at overwintering and budding stages (I2) and N application rate of 200 kg/hm2 (N2). This method overcomes the limitations of subjective and objective weighting methods, and made the evaluation results more reasonable. The finding can provide a reference for the application of water and N application in winter oilseed rape production in semi-arid areas of Northwest China and other regions with similar environments.

In both arid and semi-arid regions, adopting field mulching can effectively optimize soil moisture distribution, enhance crop yields, and improve water productivity. While acknowledging its advantages, field mulching seems insufficient for maintaining high crop productivity due to the increasing frequency of extreme weather. Furthermore, drought often coincides with critical crop growth stages, necessitating the implementation of agricultural irrigation to ensure normal crop growth. Accordingly, we conducted a three-year field experiment from 2021 to 2023 including three typical field mulching methods (no mulching, NM; straw mulching, SM; plastic film mulching, FM) and three supplementary irrigation strategies (irrigated at the branching stage (V4), W1; irrigated at the pod-filling stage (R2), W2; irrigated at both the V4 and R2 stage, W3). Throughout the entire growth period, we monitored soil moisture conditions for each treatment, measured leaf physiological parameters at crucial growth stages, and assessed soybean yields and water productivity (WP). Our findings indicated that, relative to SM and NM, FM maintains optimal soil moisture balance, augments chlorophyll content, and enhances photosynthesis, resulting in an average yield increase of 17.0% and 38.3% over three growing seasons. Additionally, supplementary irrigation also significantly affects the growth and seed yield of soybean. FMW2 achieved the higher seed yield (4307.5 kg ha−1, 3-year averaged), had insignificant difference with the highest seed yield of 4568.6 kg ha−1, both significantly higher than other treatments. Similarly, the leaf area index, chlorophyll content, net photosynthetic rate (Pn) and transpiration rate (Tr) also presented insignificant difference between FMW2 and FMW3, while WUEleaf (Pn/Tr) of FMW2 obviously higher than that of FMW3. As a result, FMW2 achieved the highest WP of 12.2 kg ha−1 mm−1 over the three growing seasons, compared to the three-year average of the other treatments, the increase ranges from 5.6% to 46.7%. In summary, the FMW2 treatment optimized water distribution to meet the water demands of soybeans during the reproductive growth stages, achieving a beneficial balance between soybean seed production and WP by regulating leaf functional parameters. Future research will explore more specific irrigation scheduling techniques (e.g., precision irrigation, deficit irrigation, and sensor-based irrigation management systems) while integrating innovative agricultural film materials (e.g., biodegradable films) to further enhance crop resilience and productivity under evolving climatic conditions.

The multiple traveling salesman problems (MTSP), which arise from real world problems, are essential in urban logistics. Variations such as MinMax-MTSP and Bounded-MTSP aim to distribute workload evenly among salesmen and impose constraints on visited cities, respectively. Branch-and-bound (B&B) provides an exact algorithm solution for these problems. The Learn to Branch (L2B) approach guides branch node selection through deep learning. In this study, we utilize mathematical modeling of Bipartite Graph Neural Network (BiGNN) and an attention mechanism to support B&B in exploring solution spaces through imitation learning. The problems are framed to formulate mixed integer linear programming, which is different from conventional algorithms. It is proposed that a bipartite graph network approach makes a feature representation by setting a structure of constraints and variables. Experimental results showed that our model can generate more accurate solutions than three benchmark models. The BiGNN model can effectively learn the strong branch strategy, which reduces solution time by replacing complex calculations with fast approximations. Additionally, the small-scale instances model can be applied to larger-scale ones.

Against the backdrop of the partially idle resources of conventional railways and the continuous growth of suburban leisure tourism demand, it is required to develop railway tourism by utilizing the disused resources of conventional railways in China. Therefore, restoring, analyzing, and evaluating the visual landscapes seen when traveling on conventional trains are extremely important. The innovation of this study is proposing a dynamic visual landscape interface for disused railways, which establishes a connection between the “seeing” and “perceiving” for passengers and describes the visual landscape they observe. By analyzing the dynamic visual factors of passengers and combining DEM data, the temporal-spatial relationship of the visual landscapes along the railway is described as a dynamic visual landscape interface model. Based on this, the study proposes criteria and indicators for analyzing and evaluating the dynamic visual landscapes of railways, using typical landscapes along the Jingmen railway as an example for evaluation and validation. The research results provide analytical and decision-making tools for repurposing disused railways as tourist railways.

Abstract Eukaryotic five-methylcytosine (m5C) is an important regulator of viral RNA splicing, stability, and translation. However, its role in HBV replication remains largely unknown. In this study, functional m5C sites are identified in hepatitis B virus (HBV) mRNA. The m5C modification at nt 1291 is not only indispensable for Aly/REF export factor (ALYREF) recognition to promote viral mRNA export and HBx translation but also for the inhibition of RIG-I binding to suppress interferon-β (IFN-β) production. Moreover, NOP2/Sun RNA methyltransferase 2 (NSUN2) catalyzes the addition of m5C to HBV mRNA and is transcriptionally downregulated by the viral protein HBx, which suppresses the binding of EGR1 to the NSUN2 promoter. Additionally, NSUN2 expression correlates with m5C modification of type I IFN mRNA in host cells, thus, positively regulating IFN expression. Hence, the delicate regulation of NSUN2 expression induces m5C modification of HBV mRNA while decreasing the levels of m5C in host IFN mRNA, making it a vital component of the HBV life cycle. These findings provide new molecular insights into the mechanism of HBV-mediated IFN inhibition and may inform the development of new IFN-α based therapies.

Abstract Introduction Durvalumab is a check‐point inhibitor against programmed death ligand‐1 (PD‐L1), and anlotinib is a new orally administered multitarget tyrosine kinase inhibitor (TKI). Both agents have been approved in China. Preclinical and clinical trials have suggested that antiangiogenic therapy has the potential to alleviate immunosuppression and showed synergetic effect when combined with ICIs. However, it is unclear that whether this combination is effective when initiated as maintenance treatment in ES‐SCLC patients. Methods This is a multicenter, randomized, phase II study. A total of 64 eligible patients who do not experience disease progression after four cycles platinum‐based chemotherapy combined with durvalumab will be randomized to durvalumab with anlotinib or durvalumab alone until disease progression, withdrawal of consent, or unacceptable toxicity. The primary endpoint is PFS (from randomization); secondary endpoint was OS and PFS (from diagnosis), objective response rate (ORR); disease control rate (DCR) and duration of response (DOR), safety and tolerability assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Discussion We conduct a phase II study to investigate the safety and efficacy of durvalumab combined with anlotinib as maintenance treatment in ES‐SCLC patients.

Abstract Monitoring extent and severity is vital in the ulcerative colitis (UC) follow-up, however, current assessment is complex and low cost-effectiveness. We aimed to develop a routine blood-based clinical decision support tool, Jin’s model, to investigate the extent and severity of UC. The multicentre retrospective cohort study recruited 975 adult UC inpatients and sub-grouped into training, internal validation and external validation set. Model was developed by logistics regression for the extent via Montreal classification and for the severity via Mayo score, Truelove and Witts score (TWS), Mayo endoscopic score (MES) and Degree of Ulcerative colitis Burden of Luminal Inflammation (DUBLIN) score. In Montreal classification, left-sided and extensive versus proctitis model achieved area under the receiver operating characteristic curve (AUROC) of 0.78 and 0.81 retrospectively. For severity, Mayo score model, TWS model, MES model and DUBLIN score model achieved an AUROC of 0.81, 0.70, 0.74 and 0.70 retrospectively. The models also were evaluated with satisfactory calibration and clinical unity. Jin’s model was free with open access at http://jinmodel.com:3000/ . Jin’s model is a noninvasive, convenient, and efficient approach to assess the extent and severity of UC.

Abstract Background Preliminary evidence suggests that several headache disorders may be associated with glymphatic dysfunction. However, no studies have been conducted to examine the glymphatic activity in migraine chronification. Purposes To investigate the glymphatic activity of migraine chronification in patients with episodic migraine (EM) and chronic migraine (CM) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. Methods In this cross-sectional study, patients with EM, CM, and healthy controls (HCs) were included. All participants underwent a standard brain magnetic resonance imaging (MRI) examination. Bilateral DTI-ALPS indexes were calculated for all participants and compared among EM, CM, and HC groups. Correlations between the DTI-ALPS index and clinical characteristics were analyzed. Results A total of 32 patients with EM, 24 patients with CM, and 41 age- and sex-matched HCs were included in the analysis. Significant differences were found in the right DTI-ALPS index among the three groups (p = 0.011), with CM showing significantly higher values than EM (p = 0.033) and HCs (p = 0.015). The right DTI-ALPS index of CM group was significantly higher than the left DTI-ALPS index (p = 0.005). And the headache intensity was correlated to DTI-ALPS index both in the left hemisphere (r = 0.371, p = 0.011) and in the right hemisphere (r = 0.307, p = 0.038), but there were no correlations after Bonferroni correction. Conclusions Glymphatic system activity is shown to be increased instead of impaired during migraine chronification. The mechanism behind this observation suggests that increased glymphatic activity is more likely to be a concomitant phenomenon of altered vascular reactivity associated with migraine pathophysiology rather than a risk factor of migraine chronification.

The thermal performance of rural building envelopes is mostly non-standardized in Northern China, resulting in significant heat loss. In this study, we take, as an example, the central area of Liaoning province, with the objective of proposing some low-cost and energy-efficient solutions. Through our investigations, we found that heating energy consumption was reduced by 20% and construction costs increased by less than CNY 8000 (USD 1108), which can be accepted by rural residents. In order to achieve this target, the NSGA-II algorithm integrated with Rhino + Grasshopper and EnergyPlus simulation kernel was used to establish a thermal performance optimization model for the heat transfer of rural building envelopes in this severe cold region. Among the above-calculated Pareto optimal solutions, the recommended thickness of insulation layers for room floors, roofs, and external walls was about 70 mm, 50 mm, and 40 mm, respectively. Furthermore, we tried to reduce the window-to-wall ratio as much as possible. Finally, based on both the lower building renovation cost and energy-saving rate, three technical solutions from which rural residents could select, according to their specific needs, are put forward.

Background Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard treatment for patients with non-small cell lung cancer (NSCLC) lacking driver gene mutations. Reliable biomarkers are essential for predicting treatment outcomes. Emerging evidence from various cancers suggests that early assessment of serum metabolites could serve as valuable biomarkers for predicting outcomes. This study aims to identify metabolites linked to treatment outcomes in patients with advanced NSCLC undergoing first-line or second-line therapy with programmed cell death 1 (PD-1) inhibitors plus chemotherapy.Method 200 patients with advanced NSCLC receiving either first-line or second-line PD-1 inhibitor plus chemotherapy, and 50 patients undergoing first-line chemotherapy were enrolled in this study. The 200 patients receiving combination therapy were divided into a Discovery set (n=50) and a Validation set (n=150). These sets were further categorized into respond and non-respond groups based on progression-free survival PFS criteria (PFS≥12 and PFS1 and p

Abstract Peptides with suitable aggregation behavior and electrical properties are potential siRNA delivery vectors. However, identifying suitable peptides with ideal delivery and safety features is difficult owing to the variations in amino acid sequences. Here, a holistic program based on computer modeling and single‐cell RNA sequencing (scRNA‐seq) is used to identify ideal siRNA delivery peptides. Stage one of this program consists of a sequential screening process for candidates with ideal assembly and delivery ability; stage two is a cell subtype‐level analysis program that screens for high in vivo tissue safety. The leading candidate peptide selected from a library containing 12 amino acids showed strong lung‐targeted siRNA delivery capacity after hydrophobic modification. Systemic administration of these compounds caused the least damage to liver and lung tissues and has little impact on macrophage and neutrophil numbers. By loading STAT3 siRNA, strong anticancer effects are achieved in multiple models, including patient‐derived xenografts (PDX). This screening procedure may facilitate the development of peptide‐based RNA interference (RNAi) therapeutics.

The drag coefficient of the sea surface is crucial for the exchange of momentum between the ocean and atmosphere. The wave state significantly influences the variability of the drag coefficient. In the past, researchers commonly employed single-parameterization methods to describe this influence. However, the influence of wave conditions on drag coefficient is complex and variable, and it is difficult to accurately describe it with a single parameter alone. Wave age represents the ability of wind-induced waves to input energy, while wave steepness reflects the stability of the waves. By simultaneously considering wave age and wave steepness, a more accurate characterization of the dynamic nature of waves can be achieved. Additionally, the presence of sea spray profoundly impacts the distribution of the momentum flux between the ocean and atmosphere, thereby influencing the drag coefficient of the sea surface. In this study, we established a novel sea spray generation function that bases on both the wind speed and wave states (wave steepness and wave age). Considering this function, the momentum flux of sea spray droplets was analyzed under different wave states. Moreover, with increasing wave age or wave steepness, the effective sea surface drag coefficient is attenuated at low to moderate wind speeds. Considering the challenge of simultaneously obtaining wave age and wave steepness data, this paper proposes a relationship equation between the two wave state parameters. When the wave age is greater than 0.4, the correlation between the wave age and the wave steepness is strong. As the wind speed increases from low to high, there is a noticeable decrease in the effective sea surface drag coefficient with the corresponding increase in wave age. When the wave age is less than 0.4, the wave steepness reaches a maximum value, and the effective sea surface drag coefficient increases with the increase of the wave age at medium and low wind speed. With further increases in wind speed, the momentum flux derived from the air also increases. Simultaneously, the effective sea surface drag coefficient exhibits a decrease as wave age increases.

Maximizing billboard coverage with limited resources and different objective goals plays a vital role in social activities. The Maximal Coverage Billboard Location Problem (MCBLP) is complex, especially for multi-objective functions. A multi-objective spatial optimization model was developed using mixed-integer linear programming based on MCBLP to formulate the spatial optimization problem of determining billboard locations. Combining the distinctive features of location problems, we have developed a new approach called ReCovNet that utilizes Deep Reinforcement Learning (DRL) to solve the MCBLP. We applied the ReCovNet to address a real-world billboard location problem in New York City. To assess its performance, we implemented various algorithms such as Gurobi solver, Genetic Algorithm (GA) and a deep learning baseline called Attention Model (AM). The Gurobi reports the optimal solutions, while GA and AM serve as benchmark algorithms. Our proposed approach achieves a good balance between efficiency and accuracy and effectively solves MCBLP. The ReCovNet introduced in our study has potential to improve advertising effectiveness, and our proposed approach offers novel insights for addressing the MCBLP.

IntroductionPositional vertigo and nystagmus are the main symptoms and signs of dizziness, respectively. Despite the clinical utility of the supine roll test (SRT) and null point (NP) in diagnosing light cupula, a type of positional vertigo, there exists a notable gap in the literature concerning the comprehensive evaluation of lateralization values based on various nystagmus characteristics and the intensity of direction-changing positional nystagmus (DCPN) in the SRT, particularly in comparison to the NP. Additionally, limited data on abnormal canal paresis (CP) in light cupula patients underscores the need for further research with a larger patient population to elucidate this mechanism. This study aims to investigate the characteristics of positional nystagmus and lateralization of the horizontal semicircular canal (HSCC) light cupula, which is a type of positional vertigo and nystagmus that is poorly understood.MethodsEighty-five patients (17 males, 68 females; mean age, 60.9 years) with light cupula were reviewed. We summarized the characteristics of spontaneous nystagmus and positional nystagmus, including supine positioning nystagmus, bow nystagmus, and lean nystagmus. Then, the side of the NP was identified as the affected side, and the values of the fast phase direction of the spontaneous nystagmus, supine positioning nystagmus, bow nystagmus, and lean nystagmus, as well as the intensity of the DCPN in the SRT, were used to diagnose the affected sides. Caloric testing was also performed for some patients.ResultsLight cupula was observed in 5.7% of the patients with positional nystagmus. The frequencies of supine positioning nystagmus (88.2%), bow nystagmus (90.6%), and lean nystagmus (83.5%) were higher than spontaneous nystagmus (61.2%) (p 0.05). However, the accuracy rate of lateralization through the sides with more vigorous DCPN in the SRT was 63.5%, significantly lower than through NP (p < 0.001). Particularly in patients with supine positioning nystagmus (n = 75), the rate was only 58.7% (p < 0.001). However, the rate was 100% in patients without supine positioning nystagmus (n = 10). Among the 70 patients who underwent caloric testing, 37 had abnormal CP, and the sides of the reduced caloric reaction were ipsilateral to the affected sides of the light cupula in 83.8% of the patients.ConclusionBesides utilizing the NP to determine the affected side, the fast phase direction of the bow nystagmus or lean nystagmus can also aid in identification. However, a simple comparison of the intensity of DCPN in SRT cannot provide accurate lateralization, especially in patients with supine positioning nystagmus. There is a high incidence of CP on the affected side of the light cupula.

Abstract Background Amygdala, an essential element of the limbic system, has served as an important structure in pain modulation. There is still a lack of clarity about altered cerebral perfusion of amygdala in migraine. This study aimed to investigate the perfusion variances of bilateral amygdala in episodic migraine (EM) and chronic migraine (CM) using multi-delay pseudo-continuous arterial spin-labeled magnetic resonance imaging (pCASL-MRI). Methods Twenty-six patients with EM, 55 patients with CM (33 CM with medication overuse headache (MOH)), and 26 age- and sex-matched healthy controls (HCs) were included. All participants underwent 3D multi-delay pCASL MR imaging to obtain cerebral perfusion data, including arrival-time-corrected cerebral blood flow (CBF) and arterial cerebral blood volume (aCBV). The CBF and aCBV values in the bilateral amygdala were compared among the three groups. Correlation analyses between cerebral perfusion parameters and clinical variables were performed. Results Compared with HC participants, patients with CM were found to have increased CBF and aCBV values in the left amygdala, as well as increased CBF values in the right amygdala (all P 0.05). In patients with CM, the increased perfusion parameters of bilateral amygdala were positively correlated with MIDAS score after adjustments for age, sex, and body mass index (BMI). Conclusion Hyperperfusion of bilateral amygdala might provide potential hemodynamics evidence in the neurolimbic pain network of CM.

With an advancement in global climate change, the frequency of extreme climatic events, such as high temperature, drought, and flooding, has increased. Meanwhile, outbreaks of crop fungal diseases are becoming more frequent and serious, and crop growth and food production are seriously threatened. This article focuses on the climate change-related aggravation of crop fungal diseases; summarizes the progress in research on the impact of climate change on soil-borne fungal diseases, air-borne fungal diseases, and seed-borne fungal diseases; and discusses the conventional methods for diagnosing crop fungal diseases. On the basis of comparative analysis, the concept of ecological control is proposed; ecological control can maintain the dynamic balance of crop–biology–soil, provide a good environment for the healthy growth of crops, and provide a new fungal disease control method in the context of climate change.

The desert locust, Schistocerca gregaria (Forsk., 1775), stands as one of the most pervasive pests globally, inflicting extensive damage across Asia and Africa. Facilitated by intercontinental migration, the desert locust engages in population exchange between different source areas, perpetuating its widespread proliferation. Despite the wind being recognized as a key factor during migration events, elucidating its precise influence on intercontinental migration has remained elusive. In this study, we scrutinized monitoring data sourced from the FAO monitoring system, pinpointing 13 desert locust events featuring intercontinental migrations since 1967. From these events, four migration routes were summarized, traversing the Red Sea (RS-WE and RS-EW) and the northern Indian Ocean (IO-WE and IO-EW). Typically, RS-WE and IO-EW migrations occurred between December and March, whereas RS-EW and IO-WE migrations were observed from May to June and April to July, respectively. Our examination of wind field data spanning the past 15 years revealed that wind direction and speed facilitated intercontinental migrations. Furthermore, migration trajectory modeling indicated that desert locusts might exhibit migratory behavior both during the day and at night in the cases of RS-WE and RS-EW, with cross-oceanic migration potentially lasting for a week for IO-WE and IO-EW. In summary, our study identifies four migration routes for the intercontinental migration of the desert locust, providing crucial support for the scientific prediction of its occurrence and contributing to international food security efforts.

Abstract Objective To explore whether MRI‐visible enlarged perivascular spaces (EPVS) are associated with migraine and may serve as a predictor of migraine. Then further explore its correlation with migraine chronification. Methods A total of 231 participants (healthy control [HC] = 57, episodic migraine [EM] = 59, chronic migraine [CM] = 115) were included in this case–control study. A 3T MRI device and the validated visual rating scale were used to assess the grades of EPVS in centrum semiovale (CSO), midbrain (MB), and basal ganglia (BG). Comparisons between the two groups were made using the chi‐square or Fisher's exact tests to initially determine whether high‐grade EPVS were associated with migraine and migraine chronification. A multivariate logistic regression model was constructed to further investigate the role of high‐grade EPVS in migraine. Results The prevalence of high‐grade EPVS in CSO and MB were significantly higher in patients with migraine than in HCs (CSO: 64.94% vs. 42.11%, P = 0.002; MB: 55.75% vs. 29.82%, P = 0.001). Subgroup analysis showed no statistical difference between patients with EM and CM (CSO: 69.94% vs. 62.61%, P = 0.368; MB: 50.85% vs. 58.26%, P = 0.351). Individuals with high‐grade EPVS in CSO (odds ratio [OR]: 2.324; 95% confidence interval [CI]: 1.136–4.754; P = 0.021) and MB (OR: 3.261; 95% CI: 1.534–6.935; P = 0.002) were more likely to suffer from migraine. Interpretation This case–control study showed that high‐grade EPVS in CSO and MB in clinical practice with the underlying mechanism of dysfunction of the glymphatic system could be a predictor of migraine, but no significant correlation had been found with migraine chronification.

ObjectivesNormal commitment of the endoderm of the third pharyngeal pouch (3PP) is essential for the development and differentiation of the thymus. The aim of this study was to investigate the role of transcription factor HOXA3 in the development and differentiation of 3PP endoderm (3PPE) from human embryonic stem cells (hESCs).MethodsThe 3PPE was differentiated from hESC-derived definitive endoderm (DE) by mimicking developmental queues with Activin A, WNT3A, retinoic acid and BMP4. The function of 3PPE was assessed by further differentiating into functional thymic epithelial cells (TECs). The effect of HOXA3 inhibition on cells of 3PPE was subsequently investigated.ResultsA highly efficient approach for differentiating 3PPE cells was developed and these cells expressed 3PPE related genes HOXA3, SIX1, PAX9 as well as EpCAM. 3PPE cells had a strong potential to develop into TECs which expressed both cortical TEC markers K8 and CD205, and medullary TEC markers K5 and AIRE, and also promoted the development and maturation of T cells. More importantly, transcription factor HOXA3 not only regulated the differentiation of 3PPE, but also had a crucial role for the proliferation and migration of 3PPE cells. Our further investigation revealed that HOXA3 controlled the commitment and function of 3PPE through the regulation of Wnt signaling pathway by activating EPHB2.ConclusionOur results demonstrated that HOXA3 functioned as the on-off switch to regulate the development of hESC-derived 3PPE through EPHB2-mediated Wnt pathway, and our findings will provide new insights into studying the development of 3PP and thymic organ in vitro and in vivo.

ObjectiveTo investigate the effect and clinical significance of Delphian lymph nodes (DLN) on the factors influencing papillary thyroid cancer (PTC) to provide individualized guidance for the surgical treatment of thyroid cancer.MethodsRelevant studies from PubMed, Web of Science, the Cochrane Library, Embase, and China National Knowledge Infrastructure databases were searched until February 13, 2023. Stringent selection parameters were used to obtain included data and homogeneous articles. Analyses were performed using Revman 5.4 and SPSS software. A P-value of < 0.05 was considered statistically significant.ResultsFive studies were finally included in this study. The results revealed a higher risk of DLN metastasis (DLNM) in patients with tumor size >1cm, multifocality, and extrathyroidal extension (ETE) of the thyroid. The risk of central lymph node metastasis (CLNM) was 11.25 times higher in DLN-positive patients with PTC than in DLN-negative (OR = 11.25, 95% CI: 8.64–14.64, P < 0.05) patients. The risk of LLNM was 5.57 times higher in DLN-positive patients with PTC than in DLN-negative (OR = 5.57, 95% CI: 4.57–6.78, P < 0.001) patients. The risk of postoperative recurrence in DLN-positive patients with PTC was 3.49 times higher (OR = 3.49, 95% CI: 1.91–6.38, P < 0.001) than in DLN-negative patients with PTC.ConclusionPatients with tumor size >1 cm in diameter, multifocality, and ETE have an increased risk for DLN development. DLN-positive patients with central and lateral cervical lymph node metastasis and postoperative recurrence are at higher risk than DLN-negative patients.

Abstract Background and purpose The pathogenesis of new daily persistent headache (NDPH) is not fully understood. We aim to map aberrant functional connectivity (FC) in patients with NDPH using resting-state functional magnetic resonance imaging (MRI). Methods Brain structural and functional MRI data were acquired from 29 patients with NDPH and 37 well-matched healthy controls (HCs) in this cross-sectional study. Region of interest (ROI) based analysis was used to compare FC between patients and HCs, with 116 brain regions in the automated anatomical labeling (AAL) atlas were defined as seeds. The correlations between aberrant FC and patients’ clinical characteristics, and neuropsychological evaluation were also investigated. Results Compared with HCs, patients with NDPH showed increased FC in the left inferior occipital gyrus, right thalamus and decreased FC in right lingual gyrus, left superior occipital gyrus, right middle occipital gyrus, left inferior occipital gyrus, right inferior occipital gyrus, right fusiform gyrus, left postcentral gyrus, right postcentral gyrus, right thalamus and right superior temporal gyrus. There were no correlation between FC of these brain regions and clinical characteristics, neuropsychological evaluation after Bonferroni correction (p > 0.05/266). Conclusions Patients with NDPH showed aberrant FC in multiple brain regions involved in perception and regulation of emotion and pain. Trial registration ClinicalTrials.gov Identifier: NCT05334927.

Abstract Background New daily persistent headache (NPDH) is a rare primary headache that is highly disabling. The pathophysiology of NDPH is still unclear, and we aimed to reveal the underlying mechanism of NDPH through functional magnetic resonance imaging (fMRI) analysis. Methods In this cross-sectional study, thirty patients with NDPH and 30 healthy controls (HCs) were recruited. The blood oxygen level-dependent (BOLD) sequences of all participants were obtained using the GE 3.0 T system. We performed ReHo, ALFF (conventional band: 0.01–0.08 Hz, slow-5: 0.01–0.027 Hz, slow-4: 0.027–0.073 Hz) and seed-based to the whole brain functional connectivity (FC) analysis in the NDPH and HC groups. The sex difference analysis of ReHo, ALFF, and FC values was conducted in the NDPH group. We also conducted Pearson’s correlation analysis between ReHo, ALFF, FC values and clinical characteristics (pain intensity, disease duration, HIT-6, GAD-7, PHQ-9, and PSQI scores). Results Both increased ReHo (PFWE-corr = 0.012) and ALFF values (0.01–0.08 Hz, PFWE-corr = 0.009; 0.027–0.073 Hz, PFWE-corr =0.044) of the left middle occipital gyrus (MOG_L) were found in the NDPH group compared to the HC group. There was no significant difference in FC maps between the two groups. Compared to the HC group, no difference was found in ReHo (p = 0.284), ALFF (p = 0.246), and FC (p = 0.118) z scores of the MOG_L in the NDPH group. There was also no sex difference in ReHo (p = 0.288), ALFF (p = 0.859), or FC z score (p = 0.118) of the MOG_L in patients with NDPH. There was no correlation between ReHo, ALFF, FC z scores and clinical characteristics after Bonferroni correction (p

With the rapid advancements in computer vision, using deep learning for strawberry disease recognition has emerged as a new trend. However, traditional identification methods heavily rely on manual discernment, consuming valuable time and imposing significant financial losses on growers. To address these challenges, this paper presents BerryNet-Lite, a lightweight network designed for precise strawberry disease identification. First, a comprehensive dataset, encompassing various strawberry diseases at different maturity levels, is curated. Second, BerryNet-Lite is proposed, utilizing transfer learning to expedite convergence through pre-training on extensive datasets. Subsequently, we introduce expansion convolution into the receptive field expansion, promoting more robust feature extraction and ensuring accurate recognition. Furthermore, we adopt the efficient channel attention (ECA) as the attention mechanism module. Additionally, we incorporate a multilayer perceptron (MLP) module to enhance the generalization capability and better capture the abstract features. Finally, we present a novel classification head design approach which effectively combines the ECA and MLP modules. Experimental results demonstrate that BerryNet-Lite achieves an impressive accuracy of 99.45%. Compared to classic networks like ResNet34, VGG16, and AlexNet, BerryNet-Lite showcases superiority across metrics, including loss value, accuracy, precision, F1-score, and parameters. It holds significant promise for applications in strawberry disease identification.

Enterotoxigenic Escherichia coli (ETEC) infections undeniably continue to have substantial morbidity and mortality in younger children; however, limited data are available on the disease burden of older children and adults and on ETEC epidemiology by geographical location at the subnational level. Facility-based surveillance over the years was established to identify patients with ETEC diarrhea in two geographically distinct areas in rural Bangladesh, Chhatak in the north and Mathbaria in the southern coastal area. ETEC was highly prevalent in both areas, while the proportions, toxin types and colonization factors varied by location, season and age groups. Children < 5 years old and adults between 20 and 60 years old were at the highest risk of ETEC diarrhea which required urgent care. This study underscores the importance of capturing subnational and seasonal variations in ETEC epidemiology. ETEC vaccine developers and public health stakeholders may need to target adults between 20 and 60 years of age in addition to young children as new vaccines currently under development become licensed and introduction begins.

ObjectiveThe workers in emerging manufacturing are at decreased risk of traditional occupational diseases, while probably at increased risk of work-related musculoskeletal disorders (WMSDs). This study aimed to investigate the prevalence and risk factors of WMSDs among emerging manufacturing workers in Beijing.MethodsA total of 3,359 valid questionnaires were collected from 10 enterprises in the electronics, pharmaceutical, and motor manufacturing industries. The prevalence of WMSDs was assessed using the Nordic Musculoskeletal Questionnaire. The work posture load was evaluated through a questionnaire.ResultsThe results showed that the highest prevalence of WMSDs was observed in part of the neck (15.0%), followed by the lower back (12.5%), shoulders (11.2%), and upper back (7.1%). Female workers, workers aged older than 35 years, workers with a BMI of ≥28 kg/m2, longer working experience, never exercised had a higher prevalence of WMSDs. Logistic regression analysis showed that female workers, workers aged older than 35 years, with a middle school education and college degree, and workers who never exercised had a higher risk of WMSDs. In addition, workers who sat for long during work, worked hard with upper limbs or hands, worked in uncomfortable postures, and performed repetitive operations were positively related with the increased risk of WMSDs.ConclusionThese findings suggested that WMSDs were prevalent among emerging manufacturing workers in Beijing, China, while efforts should be made to reshape the risk factors associated with WMSDs, such as prolonged sitting, uncomfortable positions, and repetitive operations. Encouraging exercise and promoting ergonomic interventions probably be also benefit to induce the risk of WMSDs.

Objective: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated inflammatory disorder of the nasal mucosa, and the impact of ozone on AR is gaining increasing attention. Although NOD-like receptor thermal protein domain associated protein 3 (NLRP3) plays a crucial role in the pathogenesis of AR, its regulatory mechanisms in ozone-induced exacerbation remain unclear. Therefore, we explored the impact of ozone inhalation on inflammation in AR and investigated the regulatory mechanisms involving NLRP3. Methods: Fifty female Sprague–Dawley rats were selected and divided into five groups: normal control (NC), normal with ozone exposure (NE), AR model, AR with ozone exposure (ARE), and ARE treated with the NLRP3 inhibitor MCC950 (ARE+MCC950). Behavioral changes were observed in the rats, and the expression of NLRP3, active-caspase 1, and GSDMD-N was detected by western blotting. The expression levels of interleukin (IL)− 4, IL-5, IL-13, IL-1β, and ovalbumin-specific IgE (OVA-sIgE) in nasal lavage fluid as well as IL-6 in the serum were measured by ELISA. The expression and distribution of NLRP3 and IL-1β in nasal mucosal tissue were detected by immunohistochemistry, and pathological changes and eosinophilic infiltration in nasal mucosal tissue were observed by hematoxylin and eosin (HE) staining. The effects of ozone exposure on inflammation in the nasal mucosal tissue of rats with AR and the relationship between NLRP3 and inflammation were analyzed. Results: Upregulation of NLRP3 was observed in the AR rat model, and ozone further aggravated the expression of NLRP3 in the nasal mucosal tissue. Compared to the AR, NC, and NE groups, NLRP3 inflammasomes were activated in the ARE group, and the expression levels of related indexes active-caspase 1 and GSDMD-N were significantly increased; the expression levels of Th2 inflammatory factors IL-4, IL-5, IL-13, and OVA-sIgE were increased, and inflammatory factors such as IL-1β and IL-6 expression was also significantly increased. HE staining revealed that ozone aggravated damage to the nasal mucosal tissue in AR. Compared with the ARE group, the expression of NLRP3 inflammasomes was downregulated, sneezing and scratching symptoms were reduced, inflammatory indicators in nasal lavage fluid were decreased, and nasal mucosal tissue damage was alleviated in rats in the ARE+MCC950 group. Conclusion: Ozone exposure significantly increased the inflammatory response in an animal model of AR. MCC950 can selectively inhibit the expression of NLRP3, inhibit the activity of inflammasomes, and reduce nasal mucosal inflammation by regulating the NLRP3-caspase-1-IL-1β pathway.

IntroductionLymph node metastasis in patients with papillary thyroid carcinoma (PTC) is associated with postoperative recurrence. Recently, most studies have focused on the evaluation of recurrence in patients with late-stage PTC, with limited data on those with early-stage PTC. We aimed to assess the relationship between lymph node ratio (LNR) and recurrence in low-to-intermediate-risk patients and validate its diagnostic efficiency in both structural (STR) and biochemical recurrence (BIR).MethodsClinical data of patients with PTC diagnosed at the Affiliated Hospital of Jining Medical University were retrospectively collected. The optimal LNR cut-off values for disease-free survival (DFS) were determined using X-tile software. Predictors were validated using univariate and multivariate Cox regression analyses.ResultsLNR had a higher diagnostic effectiveness than metastatic lymph nodes in patients with low-to-intermediate recurrence risk N1a PTC. The optimal LNR cutoff values for STR and BIR were 0.75 and 0.80, respectively. Multivariate Cox regression analysis showed that LNR≥0.75 and LNR≥0.80 were independent factors for STR and BIR, respectively. The 5-year DFS was 90.5% in the high LNR (≥0.75) and 96.8% in low LNR (

BackgroundGastrointestinal bleeding (GIB) is a common condition in clinical practice, and predictive models for patients with GIB have been developed. However, assessments of in-hospital mortality due to GIB in the intensive care unit (ICU), especially in critically ill patients, are still lacking. This study was designed to screen out independent predictive factors affecting in-hospital mortality and thus establish a predictive model for clinical use.MethodsThis retrospective study included 1,442 patients with GIB who had been admitted to the ICU. They were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) 1.0 database and divided into a training group and a validation group in a ratio of 7:3. The main outcome measure was in-hospital mortality. Least absolute shrinkage and section operator (LASSO) regression was used to screen out independent predictors and create a nomogram.ResultsLASSO regression picked out nine independent predictors: heart rate (HR), activated partial thromboplastin time (aPTT), acute physiology score III (APSIII), sequential organ failure assessment (SOFA), cerebrovascular disease, acute kidney injury (AKI), norepinephrine, vasopressin, and dopamine. Our model proved to have excellent predictive value with regard to in-hospital mortality (the area under the receiver operating characteristic curve was 0.906 and 0.881 in the training and validation groups, respectively), as well as a good outcome on a decision curve analysis to assess net benefit.ConclusionOur model effectively predicts in-hospital mortality in patients with GIB, indicating that it may prove to be a valuable tool in future clinical practice.

Background Treatment options are limited for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after treatment failure with EGFR tyrosine kinase inhibitors (TKIs). This multicenter open-label, phase II study aims to evaluate the efficacy and safety of tislelizumab plus chemotherapy (cohort 1, TIS+chemo) or tislelizumab plus chemotherapy and bevacizumab (cohort 2, TIS+chemo+ beva) in EGFR-mutated non-squamous NSCLC patients who progressed on EGFR TKI therapies. Here, the primary analysis of the TIS+chemo cohort is reported.Methods In the TIS+chemo cohort, patients with EGFR-sensitizing mutations with prior EGFR TKI failure received tislelizumab plus carboplatin and nab-paclitaxel as induction treatment, followed by maintenance with tislelizumab plus pemetrexed. The primary endpoint was 1-year progression-free survival (PFS) rate. The planned sample size was 66 with a historical control of 7%, an expected value of 20%, a one-sided α of 0.05, and a power of 85%.Results Between July 11, 2020 and December 13, 2021, 69 patients were enrolled. As of June 30, 2022, the median follow-up was 8.2 months. Among the 62 patients in the efficacy analysis set, estimated 1-year PFS rate was 23.8% (90% CI 13.1% to 36.2%), and its lower bound of 90% CI was higher than the historical control of chemotherapy (7%), which met the primary endpoint. The median PFS was 7.6 (95% CI 6.4 to 9.8) months. Median overall survival (OS) was not reached (95% CI 14.0 to not estimable), with a 1-year OS rate of 74.5% (95% CI 56.5% to 86.0%). The objective response rate and disease control rate were 56.5% (95% CI 43.3% to 69.0%) and 87.1% (95% CI 76.1% to 94.3%), respectively. Patients who had progressed on first-generation/second-generation and third-generation EGFR-TKIs at baseline had shorter PFS than those who progressed on first-generation/second-generation EGFR-TKIs (median 7.5 vs 9.8 months, p=0.031). Patients with positive ctDNA had shorter PFS (median 7.4 vs 12.3 months, p=0.031) than those with negative ctDNA. No grade 5 treatment-emergent adverse events (TEAEs) were observed. Grades 3–4 TEAEs occurred in 40.6% (28/69) of patients. Grades 3–4 immune-related AEs occurred in 5 (7.2%) patients.Conclusion The study met the primary endpoint for the TIS+chemo cohort. Tislelizumab plus chemotherapy is effective with an acceptable safety profile for EGFR-mutated non-squamous NSCLC after EGFR TKI failure.

In the context of cattle farm environments, intricate environmental interferences have presented challenges that impede seamless data acquisition. This paper introduces a novel approach, the integration of a fusion gate transformation mechanism and a variational autoencoder GAN, which we term GCT-VAE-GAN, aimed at enhancing low-light images from cattle farm settings. Initially, our approach involves the design of an encoding network tasked with augmenting the original images. Subsequently, we advance our methodology by formulating a generative network to effectively address the challenges of image diversification and poor image quality. Notably, the inclusion of an attention mechanism block within the FFN layer facilitates the fusion of these extracted features, resulting in the generation of high-quality images. Furthermore, to achieve proficient image discrimination, we implement a dual-discriminator structured discriminative network for the conclusive image discrimination task. The culmination of our approach involves the formulation of a comprehensive joint loss function, thereby constituting the core of the model’s loss module. Moreover, through comparative experiments, we aptly demonstrate the remarkable superiority of the GCT-VAE-GAN approach. The conducted experiments reveal the model’s consistent performance and resilience under varying illumination scenarios. The outcomes of our study underscore its significant relevance in elevating the quality of low-light images within cattle farm contexts. Furthermore, our approach exhibits the potential to enhance the efficacy of computer vision tasks, signifying a notable stride toward improved agricultural imaging techniques.

Cattle’s individual identification plays a crucial role in effectively managing large farms. To enhance agricultural efficiency, promote the digital transformation of animal husbandry, and improve animal welfare, it is essential to employ advanced identification technologies capable of real-time monitoring of cattle individual. This paper introduces a novel network called Open Pose Mask R-CNN (OP-Mask R-CNN) for individual cattle identification, which combines Open Pose with the Mask R-CNN network. Three key strategies are presented to improve the identification of individual cattle. First, optimize the number of convolutional layers in the Mask R-CNN backbone network, i.e., ResNet101. Second, introduce an Open Pose-based bovine skeleton feature extraction method. Finally, construct a fusion mechanism that combines the attention module, the convolutional block attention module (CBAM), the open pose module, and the ResNet101. Experimental results demonstrate that our proposed method achieves a 5.6% increase in recognition accuracy and improves recognition speed compared to the original Mask R-CNN model. This work strikes a balance between accuracy and complexity, facilitating the development of a lightweight bovine individual recognition technique.

Abstract A numerical analysis method of trailing edge deboning is proposed in this paper. Using this method, multiple repair parameters can be quantified by analyzing aerodynamic responses and structural characteristics of the trailing edge. This method can be applied to three types of trailing edge, including blunt trailing edge, transitional trailing edge, and pointed trailing edge. In this study, the repair parameters are divided into two types, including the internal parameters that can affect the bonding strength and the external parameters that can affect the stiffness and aerodynamic shape. The main research steps are as follows: First, a repair structure shell‐body model was developed. Second, static tensile tests were carried out using 49 specimens, covering two lap joint types and seven bonding thicknesses. Finally, nine different repaired trailing edge models were developed using Ansys/Fluent for each two two‐dimensional airfoil. A 30–40 m section of a 71 m blade was used to develop a three‐dimensional (3D) rotating model with the repaired trailing edge. The simulation results show that the two internal parameters, overlap length and the slope of adhesive joints, are the key to improving the bonding performance of the pointed trailing edge. In addition, the bonding thickness range of 1–10 mm is proved by the experiment results and numerical analysis to be sufficient for good bonding performance. Besides this, the influence of the repair height on the aerodynamic pressure distribution and lift coefficient is much greater than the repair width, and the torque and power of the repaired 3D blade model are 1.91% higher than that of the original blade. This should further help provide an effective theoretical basis for determining the repair plan for a wind turbine blade.

Abstract Introduction We aim to introduce a method using confocal scanning laser ophthalmoscopy (cSLO) images for measuring retinal vascular geometry, including vessel branch angle (BA), vessel diameter, vessel tortuosity, and fractal dimension (D f), and to elucidate the relationship between hypertension and these metrics. Methods A total of 119 participants (119 eyes) were enrolled, among which 72 were normotensive and 47 were hypertensive. Infrared cSLO images were extracted from the circular scan around the optics disc using a commercial cSLO + optical coherence tomography instrument. Preprocessed cSLO images were further analyzed using the appropriate tool/macro/plugin of ImageJ. Results Intraclass correlation coefficients of selected methods used for conducting the cSLO-based geometric analyses were all higher than 0.80. Arterial/arteriolar BA, arteriolar vessel diameter, and total D f in normotensive subjects were 85.80 ± 7.79°, 116.80 ± 12.58 μm, and 1.430 ± 0.037, respectively, significantly higher than those of hypertensive subjects (82.13 ± 10.83°, 108.2 ± 11.12 μm, and 1.361 ± 0.044, all P 0.05). Conclusion Proposed cSLO-based methods for assessing various vascular geometric parameters were highly repeatable and reproducible. Arterial/arteriolar BA, arteriolar vessel diameter, and total D f were retinal vascular parameters significantly correlated with hypertension in a negative manner.