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Abstract Electronic band structures in hydrogenated graphene are theoretically investigated by means of first-principle calculations and an effective tight-binding model. It is shown that regularly designed hydrogenation to graphene gives rise to a large band gap about 1 eV. Remarkably, by changing the spatial pattern of the hydrogenation, topologically distinct states can be realized, where the topological nontriviality is detected by $$C_2$$ C 2 parity indices in bulk and confirmed by the existence of gapless edge/interface states as protected by the mirror and sublattice symmetries. The analysis of the wave functions reveals that the helical edge states in hydrogenated graphene with the appropriate design carry pseudospin currents that are reminiscent of the quantum spin Hall effect. Our work shows the potential of hydrogenated graphene in pseudospin-based device applications.

Acoustic fish driving technology, as an auxiliary fish passage measure and a non-physical barrier, is based on the use of sound signals to prevent or regulate fish behavior. The purpose of these techniques is to guide the fish away from dangerous areas, such as the water inlets of hydroelectric power stations, spillways, and ship locks, allowing them to easily locate the entrance to the fishway, which would help improve fish passage efficiency. Studying the negative phonotaxis behavior of fish is vital for establishing non-physical barriers using acoustic characteristics. However, there has been little research on verifying the effectiveness of acoustic fish deterrence technology in field environments. Therefore, this study used alternating sound playback to conduct negative phonotaxis experiments on grass carp (Ctenopharyngodon idellus) juveniles to explore their behavioral responses to different sounds. The experimental tank (3.6 m×1.1 m×1.0 m) was created in the waters of Xialao Creek in Yichang City, Hubei Province, with an average water depth of 0.5 m and an average flow rate of 0.06 m/s. The experiment used one single-frequency sound (1 000 Hz) and five complex sounds (fish swimming, engine, short-nosed crocodile call, pile driving, and yacht sounds), with a sound pressure level of (117.69±2.77) dB re 1 μPa. The effectiveness of acoustic fish-repellent technology has been proven, but there are only a few applications in practical engineering. On the one hand, the theoretical knowledge is not comprehensive, and on the other hand, there is a gap between theoretical research and practical engineering. Moreover, there are differences in proton movement (vibration) modes between indoor and natural environments. Compared with fish in an indoor environment, fish in natural waters tend to receive sound signals by proton movement rather than sound pressure. At the same time, the distribution of the sound field in natural and indoor environments also differs; thus, field experiments are necessary for the advancement of acoustic fish-repellent technology. Globally, studies on the negative phonotaxis of fish have mainly been conducted in vitro. Detailed studies using natural open water conditions are insufficient, and further field verification experiments are needed. Therefore, this study conducted experiments in natural open water, compared the sound field changes in the natural and indoor environments, and studied negative phonotaxis behavior by observing reaction time, initial reaction time, average reaction time, phonotaxis speed, movement time ratio, and other indicators. The results showed that when the complex sounds were played, the reaction times, tone trend speed and movement time ratio of grass carp were significantly higher than that of single tone and control group (P < 0.001), and the initial reaction time and average reaction time of grass carp were significantly lower than that of single tone and control group (P < 0.001). Among the complex sounds, the grass carp stimulated by the yacht sound had the largest response times and speed, while the grass carp stimulated by the fish swimming sound had the smallest response times and speed. In the complex sound, the first response time of grass carp stimulated by yacht sound was the shortest, which was (23.40±5.13) s. The first response time of grass carp stimulated by engine sound was (146.00±7.82) s, which was significantly lower than that of other complex sounds (P < 0.05). The average response time of grass carp stimulated by the sound of yacht and pile was (26.52±3.01) s and (28.76±4.07) s, respectively. The average response time of grass carp stimulated by fish swimming sound was (64.76±17.82) s. In the complex sound, the motion time ratio of grass carp stimulated by fish swimming sound was the highest, which was (98.47±0.48)%. The motion time ratio of grass carp stimulated by engine sound was (94.58±0.54)%. There were no significant differences in reaction times, initial reaction time, average reaction time and exercise time ratio between grass carp and control group when playing single frequency tone (P > 0.05). The experimental results indicated that the five complex sounds used in this study (fish swimming, engine, short-nosed crocodile call, pile driving, and yacht sounds) all had a deterrent effect on grass carp juveniles. This study not only enriches current knowledge of the negative phonotaxis behavior of fish but also provides a scientific basis for the design and optimization of sound-based fish deterrent facilities in practical engineering.

Abstract A recent Little-Parks experiment in Kagome-structured superconductor CsV3Sb5 demonstrated resistance oscillations with period $${\phi }_{0}/3={hc}/6e$$ ϕ 0 / 3 = h c / 6 e . Here, we perform analysis based on a theory involving three $$2{{{{{\rm{e}}}}}}$$ 2 e superconductivity (SC) order parameters associated with the three reciprocal lattice vectors which connect M points of the hexagonal Brillouin zone. In a ring geometry we find that, as a series of intermediate states, phase of one SC order parameter winds 2π more or less than the other two ones around the ring, which yields local free-energy minima at integer multiples of $${\phi }_{0}/3$$ ϕ 0 / 3 . It is unveiled that the ground-state degeneracy associated with a Z2 chirality is crucial, and the Higgs-Leggett mechanism stabilizes domain walls (DWs) between chiral domains. At low temperatures DWs are expelled from the system resulting in free-energy minima only at integer multiples of $${\phi }_{0}$$ ϕ 0 . Our theory explains successfully the fractional quantization of magnetic flux $${\phi }_{0}/3$$ ϕ 0 / 3 observed in experiments, which opens a door for approaching rich physics of Kagome superconductors.

Abstract Backgrounds A growing body of evidence has highlighted the interactions of lipids metabolism and immune regulation. Nevertheless, there is still a lack of evidence regarding the causality between lipids and autoimmune diseases (ADs), as well as their possibility as drug targets for ADs. Objectives This study was conducted to comprehensively understand the casual associations between lipid traits and ADs, and evaluate the therapeutic possibility of lipid-lowering drug targets on ADs. Methods Genetic variants for lipid traits and variants encoding targets of various lipid-lowering drugs were derived from Global Lipid Genetics Consortium (GLGC) and verified in Drug Bank. Summary data of ADs were obtained from MRC Integrative Epidemiology Unit (MER-IEU) database and FinnGen consortium, respectively. The causal inferences between lipid traits/genetic agents of lipid-lowering targets and ADs were evaluated by Mendelian randomization (MR), summary data-based MR (SMR), and multivariable MR (MVMR) analyses. Enrichment analysis and protein interaction network were employed to reveal the functional characteristics and biological relevance of potential therapeutic lipid-lowering targets. Results There was no evidence of causal effects regarding 5 lipid traits and 9 lipid-lowering drug targets on ADs. Genetically proxied 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) inhibition was associated with a reduced risk of rheumatoid arthritis (RA) in both discovery (OR [odds ratio] = 0.45, 95%CI: 0.32, 0.63, P = 6.79 × 10− 06) and replicate datasets (OR = 0.37, 95%CI: 0.23, 0.61, P = 7.81 × 10− 05). SMR analyses supported that genetically proxied HMGCR inhibition had causal effects on RA in whole blood (OR = 0.48, 95%CI: 0.29, 0.82, P = 6.86 × 10− 03) and skeletal muscle sites (OR = 0.75, 95%CI: 0.56, 0.99, P = 4.48 × 10− 02). After controlling for blood pressure, body mass index (BMI), smoking and drinking alchohol, HMGCR suppression showed a direct causal effect on a lower risk of RA (OR = 0.33, 95%CI: 0.40, 0.96, P = 0.042). Conclusions Our study reveals causal links of genetically proxied HMGCR inhibition (lipid-lowering drug targets) and HMGCR expression inhibition with a decreased risk of RA, suggesting that HMGCR may serve as candidate drug targets for the treatment and prevention of RA.

Abstract Understanding water saturation levels in tight gas carbonate reservoirs is vital for optimizing hydrocarbon production and mitigating challenges such as reduced permeability due to water saturation (Sw) and pore throat blockages, given its critical role in managing capillary pressure in water drive mechanisms reservoirs. Traditional sediment characterization methods such as core analysis, are often costly, invasive, and lack comprehensive spatial information. In recent years, several classical machine learning models have been developed to address these shortcomings. Traditional machine learning methods utilized in reservoir characterization encounter various challenges, including the ability to capture intricate relationships, potential overfitting, and handling extensive, multi-dimensional datasets. Moreover, these methods often face difficulties in dealing with temporal dependencies and subtle patterns within geological formations, particularly evident in heterogeneous carbonate reservoirs. Consequently, despite technological advancements, enhancing the reliability, interpretability, and applicability of predictive models remains imperative for effectively characterizing tight gas carbonate reservoirs. This study employs a novel data-driven strategy to prediction of water saturation in tight gas reservoir powered by three recurrent neural network type deep/shallow learning algorithms—Gated Recurrent Unit (GRU), Recurrent Neural Networks (RNN), Long Short-Term Memory (LSTM), Support Vector Machine (SVM), K-nearest neighbor (KNN) and Decision tree (DT)—customized to accurately forecast sequential sedimentary structure data. These models, optimized using Adam's optimizer algorithm, demonstrated impressive performance in predicting water saturation levels using conventional petrophysical data. Particularly, the GRU model stood out, achieving remarkable accuracy (an R-squared value of 0.9973) with minimal errors (RMSE of 0.0198) compared to LSTM, RNN, SVM, KNN and, DT algorithms, thus showcasing its proficiency in processing extensive datasets and effectively identifying patterns. By achieving unprecedented accuracy levels, this study not only enhances the understanding of sediment properties and fluid saturation dynamics but also offers practical implications for reservoir management and hydrocarbon exploration in complex geological settings. These insights pave the way for more reliable and efficient decision-making processes, thereby advancing the forefront of reservoir engineering and petroleum geoscience.

Abstract Background Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH. Methods The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration. Results P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH. Conclusion P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.

Abstract Widespread distribution of porcine epidemic diarrhea virus (PEDV) has led to catastrophic losses to the global pig farming industry. As a result, there is an urgent need for rapid, sensitive and accurate tests for PEDV to enable timely and effective interventions. In the present study, we develop and validate a floating gate carbon nanotubes field-effect transistor (FG CNT-FET)-based portable immunosensor for rapid identification of PEDV in a sensitive and accurate manner. To improve the affinity, a unique PEDV spike protein-specific monoclonal antibody is prepared by purification, and subsequently modified on FG CNT-FET sensor to recognize PEDV. The developed FET biosensor enables highly sensitive detection (LoD: 8.1 fg/mL and 100.14 TCID50/mL for recombinant spike proteins and PEDV, respectively), as well as satisfactory specificity. Notably, an integrated portable platform consisting of a pluggable FG CNT-FET chip and a portable device can discriminate PEDV positive from negative samples and even identify PEDV and porcine deltacoronavirus within 1 min with 100% accuracy. The portable sensing platform offers the capability to quickly, sensitively and accurately identify PEDV, which further points to a possibility of point of care (POC) applications of large-scale surveillance in pig breeding facilities.

Abstract Background Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. Methods A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4–6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. Discussion Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.

Abstract Introduction The 8th edition lung cancer staging system was the first to describe the detailed diagnosis and staging of multiple primary lung cancers (MPLC). However, the characteristics and prognosis of MPLC categorized according to the new system have not been evaluated. Method We retrospectively analyzed data from surgically treated MPLC patients in a single center from 2011 to 2013 and explored the characteristics and outcomes of different MPLC disease patterns. Results In total, 202 surgically treated MPLC patients were identified and classified into different groups according to disease categories and diagnostic time (multifocal ground glass/lepidic (GG/L) nodules: n = 139, second primary lung cancer (SPLC): n = 63, simultaneous MPLC (sMPLC): n = 171, and metachronous MPLC (mMPLC): n = 31). There were significant differences in clinical characteristics between SPLC and GG/L nodule patients and simultaneous and metachronous MPLC patients. The overall 1-, 3-, and 5-year lung cancer-specific survival rates of MPLC were 97.98%, 90.18%, and 82.81%, respectively. Five-year survival was better in patients with multiple GG/L nodules than in those with SPLC (87.94% vs. 71.29%, P

Resin-reinforced Ag sintering materials represent a promising solution for die-attach applications in high-power devices requiring enhanced reliability and heat dissipation. However, the presence of resin and intricate microstructure poses challenges to its thermal performance, and improvement strategies remain unclear. This work utilizes 3D FIB-SEM nanotomography to reconstruct the microstructure of this material under various process conditions. The analysis reveals that, even with an Ag volume fraction as low as 47.3%, Ag particles form a robust 3D network. Geometric tortuosity quantifies the effect of different sintering conditions on the Ag particle network in all spatial directions. Effective thermal conductivity is simulated based on realistic microstructure models. Results show a significant negative correlation between tortuosity and effective thermal conductivity. Increasing sintering temperature in Model B notably reduces tortuosity and enhances effective thermal conductivity. Sensitivity analysis underscores the dominant role of Ag volume fraction in regulating effective thermal conductivity. Finally, transient thermal impedance measurement of this material as a thin die-attach layer in actual high-power devices demonstrated its application potential. This article strives to explore the relationship between process, microstructure, and thermal properties of this material to provide a reference for further development.

BackgroundExploration of the benefits and timing of surgical decompression in spinal cord injury (SCI) has been a research hotspot. However, despite the higher volume and increasing emphasis on quality there remains no bibliometric view on SCI and surgical decompression. In this study, we aimed to perform bibliometric analysis to reveal the core countries, affiliations, journals, authors, and developmental trends in SCI and surgical decompression across the past 50 years.MethodsArticles and reviews were retrieved from web of science core collection between 1975 and 2024. The bibliometrix package in R was used for data analysis and visualizing.ResultsA total of 8,688 documents were investigated, indicating an ascending trend in annual publications. The USA and China played as the leaders in scientific productivity. The University of Toronto led in institutional productions. Core authors, such as Michael G. Fehlings, showed high productivity, and occasional authors showed widespread interests. Core journals like Spine and Spinal Cord served as beacons in this field. The interaction of core authors and international collaboration accentuated the cross-disciplinary feature of the field. Prominent documents emphasized the clinical significance of early decompression in 24 h post SCI.ConclusionBased on comprehensive bibliometric analysis and literature review, we identified the hotspots and future directions of this field: (1) further investigation into the molecular and cellular mechanisms to provide pre-clinical evidence for biological effects of early surgical decompression in SCI animal models; (2) further evaluation and validation of the optimal time window of surgical decompression based on large cohort, considering the inherent heterogeneity of subpopulations in complicated immune responses post SCI; (3) further exploration on the benefits of early decompression on the neurological, functional, and clinical outcomes in acute SCI; (4) evaluation of the optimal surgical methods and related outcomes; (5) applications of artificial intelligence-based technologies in spinal surgical decompression.

IntroductionNatural plants are valuable resources for exploring new bioactive compounds. Artemisia vulgaris L. is a traditional Chinese medicinal herb that has been historically used for treating multiple diseases. Active compounds isolated and extracted from A. vulgaris L. typically possess immunomodulatory and anti-inflammatory properties. Artemvulactone E (AE) is a new sesquiterpene lactone isolated and extracted from A. vulgaris L. with unclear biological activities.MethodsThe immunoregulatory effects of AE on macrophages were assessed by ELISA, RT-qPCR, immunofluorescence, and western blot assay. The effect of AE on lipopolysaccharide (LPS) -relates signaling pathways was examined by western blot assay. In zebrafish models, the larvae were yolk-microinjected with LPS to establish inflammation model and the effect of AE was evaluated by determining the survival rate, heart rate, yolk sac edema size, neutrophils and macrophages infiltration of zebrafish. The interaction between AE and Toll-like receptor 4 (TLR4) was examined by molecular docking and dynamic stimulation.ResultsAE reduced the expression and secretion of pro-inflammatory cytokines (TNF-α and IL-6), inflammatory mediators iNOS and COX-2, as well as decreases the production of intracellular NO and ROS in LPS-stimulated macrophages. In addition, AE exerted its anti-inflammatory effect synergistically by inhibiting MAPK/JAK/STAT3-NF-κB signaling pathways. Furthermore, AE enhanced the survival rate and attenuated inflammatory response in zebrafish embryos treated with LPS. Finally, the molecular dynamics results indicate that AE forms stable complexes with LPS receptor TLR4 through the Ser127 residue, thus completely impairing the subsequent activation of MAPK-NF-κB signaling.ConclusionAE exhibits notable anti-inflammatory activity and represents as a potential agent for treating inflammation-associated diseases.

PurposeThis meta-analysis aims to identify whether patients with sepsis who have persistent tachycardia despite initial resuscitation can benefit from ultrashort-acting β-blockers.Materials and methodsRelevant studies from MEDLINE, the Cochrane Library, and Embase were searched by two independent investigators. RevMan version 5.3 (Cochrane Collaboration) was used for statistical analysis.ResultsA total of 10 studies were identified and incorporated into the meta-analysis. The results showed that the administration of ultrashort-acting β-blockers (esmolol/landiolol) in patients with sepsis with persistent tachycardia despite initial resuscitation was significantly associated with a lower 28-day mortality rate (risk ratio [RR], 0.73; 95% confidence interval [CI], 0.57–0.93; and p˂0.01). Subgroup analysis showed that the administration of esmolol in patients with sepsis was significantly associated with a lower 28-day mortality rate (RR, 0.68; 95% CI, 0.55–0.84; and p˂0.001), while there was no significant difference between the landiolol and control groups (RR, 0.98; 95% CI, 0.41–2.34; and p = 0.96). No significant differences between the two groups were found in 90-day mortality, mean arterial pressure (MAP), lactate (Lac) level, cardiac index (CI), and troponin I (TnI) at 24 h after enrollment.ConclusionThe meta-analysis indicated that the use of esmolol in patients with persistent tachycardia, despite initial resuscitation, was linked to a notable reduction in 28-day mortality rates. Therefore, this study advocates for the consideration of esmolol in the treatment of sepsis in cases where tachycardia persists despite initial resuscitation.

BackgroundHigh BMI (Body Mass Index) is a significant factor impacting health, with a clear link to an increased risk of leukemia. Research on this topic is limited. Understanding the epidemiological trends of leukemia attributable to high BMI risk is crucial for disease prevention and patient support.MethodsWe obtained the data from the Global Burden of Disease Study, analyzing the ASR (age-standardized rates), including ASDR (age-standardized death rate) and age-standardized disability-adjusted life years (DALYs) rate, and estimated annual percentage change (EAPC) by gender, age, country, and region from 1990 to 2019.ResultsIn 2019, deaths and DALYs have significantly increased to 21.73 thousand and 584.09 thousand. The global age-standardized death and DALYs rates have slightly increased over the past 30 years (EAPCs: 0.34 and 0.29). Among four common leukemia subtypes, only CML (Chronic Myeloid Leukemia) exhibited a significant decrease in ASDR and age-standardized DALYs rate, with EAPC of -1.74 and -1.52. AML (Acute Myeloid Leukemia) showed the most pronounced upward trend in ASDR, with an EAPC of 1.34. These trends vary by gender, age, region, and national economic status. Older people have been at a significantly greater risk. Females globally have borne a higher burden. While males have shown an increasing trend. The regions experiencing the greatest growth in ASR were South Asia. The countries with the largest increases were Equatorial Guinea. However, It is worth noting that there may be variations among specific subtypes of leukemia. Regions with high Socio-demographic Index (SDI) have had the highest ASR, while low-middle SDI regions have shown the greatest increase in these rates. All ASRs values have been positively correlated with SDI, but there has been a turning point in medium to high SDI regions.ConclusionsLeukemia attributable to high BMI risk is gradually becoming a heavier burden globally. Different subtypes of leukemia have distinct temporal and regional patterns. This study’s findings will provide information for analyzing the worldwide disease burden patterns and serve as a basis for disease prevention, developing suitable strategies for the modifiable risk factor.

Abstract Objective To assess the prevalence and factors associated with early cognitive impairment in intracerebral hemorrhage (ICH) patients and to describe short‐term recovery trajectories among ICH patients with early cognitive impairment. Methods We prospectively enrolled ICH patients without baseline dementia in our institutions. Cognitive function was assessed using mini‐mental state examination (MMSE), and functional outcome was evaluated at discharge, 3, and 6 months after symptoms onset using the modified Rankin Scale (mRS). We used multinomial logistic regression models to investigate potential risk factors and generalized linear models to analyze the functional outcome data. Results Out of 181 patients with ICH, 167 were included in the final analysis. Early cognitive impairment occurred in 60.48% of patients with ICH. Age (odds ratio [OR] per 1‐year increase, 1.037; 95% confidence interval [CI], 1.003–1.071; p = 0.034), National Institutes of Health Stroke Scale (NIHSS) score (OR per 1‐point increase, 1.146; 95% CI, 1.065–1.233; p

Abstract Background The TRIANGLE operation benefits patients with pancreatic cancer; however, the Heidelberg triangle, where the operation occurs, contains vessels that can impact safety, especially in laparoscopic pancreaticoduodenectomy (LPD) with the TRIANGLE operation. This study aimed to identify Heidelberg triangle vessel types and their implications in pancreaticoduodenectomy (PD). Methods Retrospective collection of radiographic data was performed from January 2017 to April 2023. Three-dimensional (3D) CT reconstructions were performed on patients. Vascular types in the Heidelberg triangle were classified based on named vessels crossing its interior. The impact of these types on surgical outcomes and complications in PD with the TRIANGLE operation was assessed. Results Preoperative CT reconstruction was conducted on 184 pancreatic surgery patients. The findings revealed 99 patients (53.8%) with the type I Heidelberg triangle, lacking named vessels crossing the interior. Type II (n = 85, 46.2%), with named vessels crossing the interior, was identified. Among reconstructed patients who underwent PD with the TRIANGLE operation (n = 103), they were categorized as type I (n = 57) or type II (n = 46). The results showed that LPD patients with type II had significantly higher median intraoperative blood loss (300 mL vs. 200 mL, P = 0.030) and mean examined lymph nodes (17.2 ± 7.6 vs. 13.4 ± 5.2, P = 0.019) compared to those with type I. No significant differences were found in operative time or postoperative complications. Conclusion The presence of named vessels crossing the interior of the Heidelberg triangle was associated with increased intraoperative bleeding during LPD combined with the TRIANGLE operation. Therefore, targeted preoperative planning is required before the operation, thus improving the safety of the TRIANGLE operation in minimally invasive surgery.

Guidance commands of flight vehicles can be regarded as a series of data sets having fixed time intervals, thus guidance design constitutes a typical sequential decision problem and satisfies the basic conditions for using the deep reinforcement learning (DRL) technique. In this paper, we consider the scenario where the escape flight vehicle (EFV) generates guidance commands based on the DRL technique and the pursuit flight vehicle (PFV) generates guidance commands based on the proportional navigation method. Evasion distance is described as the minimum distance between the EFV and the PFV during the escape-and-pursuit process. For the EFV, the objective of the guidance design entails progressively maximizing the residual velocity, which is described as the EFV’s velocity when the evasion distance occurs, subject to the constraint imposed by the given evasion distance. Thus an irregular dynamic max-min problem of extremely large-scale is formulated. In this problem, the time instant when the optimal solution (i.e., the maximum residual velocity satisfying the evasion distance constraint) can be attained is uncertain and the optimum solution is dependent on all the intermediate guidance commands generated before. For solving this challenging problem, a two-step strategy is conceived. In the first step, we use the proximal policy optimization (PPO) algorithm to generate the guidance commands of the EFV. The results obtained by PPO in the global search space are coarse, despite the fact that the reward function, the neural network parameters and the learning rate are designed elaborately. Therefore, in the second step, we propose to invoke the evolution strategy (ES) based algorithm, which uses the result of PPO as the initial value, to further improve the quality of the solution by searching in the local space. Extensive simulation results demonstrate that the proposed guidance design method based on the PPO algorithm is capable of achieving a residual velocity of 67.24 m/s, higher than the residual velocities achieved by the benchmark soft actor-critic and deep deterministic policy gradient algorithms. Furthermore, the proposed ES-enhanced PPO algorithm outperforms the PPO algorithm by 2.7%, achieving a residual velocity of 69.04 m/s.

Abstract Idiopathic pulmonary fibrosis (IPF) is a globally prevalent, progressive disease with limited treatment options and poor prognosis. Because of its irreversible disease progression, IPF affects the quality and length of life of patients and imposes a significant burden on their families and social healthcare services. The use of the antifibrotic drugs pirfenidone and nintedanib can slow the progression of the disease to some extent, but it does not have a reverse effect on the prognosis. The option of lung transplantion is also limited owing to contraindications to transplantation, possible complications after transplantation, and the risk of death. Therefore, the discovery of new, effective treatment methods is an urgent need. Over recent years, various studies have been undertaken to investigate the relationship between interstitial pneumonia and lung cancer, suggesting that some immune checkpoints in IPF are similar to those in tumors. Immune checkpoints are a class of immunosuppressive molecules that are essential for maintaining autoimmune tolerance and regulating the duration and magnitude of immune responses in peripheral tissues. They can prevent normal tissues from being damaged and destroyed by the immune response. While current studies have focused on PD-1/PD-L1 and CTLA-4, PD-1/PD-L1 may be the only effective immune checkpoint IPF treatment. This review discusses the application of PD-1/PD-L1 checkpoint in IPF, with the aim of finding a new direction for IPF treatment.

Abstract Geological hazards, especially landslides and mudslides, are frequent in Caoke County, Sichuan Province, China. In September 2022, the mechanical parameters of the soil were obtained through a basic investigation of the landslide characteristics of Ni changgou. Upon that, the finite element-discrete element method was used to reconstruct the three-dimensional numerical model of the landslide on the right bank of Ni changgou, and the initiation mechanism of rainfall on landslide and the formation of debris flow impact dam process were simulated. Furthermore, the pore pressure, stability coefficient as well as displacement of the landslide body were analyzed. It turned out that with the increase of rainfall intensity, the pore water pressure value also increases, where pore water pressure rises rapidly. the slope is close to the unstable edge, Eventually, it tends to one under rainfall conditions, and due to gravity, the slide of the landslide is induced. The duration of landslide movement is about 200 s, the maximum average velocity of the landslide reaches 4.85 m/s, and the average movement distance is close to 500 m. In addition, this method is applied to the Chutougou debris flow, and the corresponding hazard analysis is added which could better show the treatment and application of debris flow in actual engineering.

Abstract Epithelial-mesenchymal transition (EMT) and proliferation play important roles in epithelial cancer formation and progression, but what molecules and how they trigger EMT is largely unknown. Here we performed spatial transcriptomic and functional analyses on samples of multistage esophageal squamous-cell carcinoma (ESCC) from mice and humans to decipher these critical issues. By investigating spatiotemporal gene expression patterns and cell–cell interactions, we demonstrated that the aberrant epithelial cell interaction via EFNB1-EPHB4 triggers EMT and cell cycle mediated by downstream SRC/ERK/AKT signaling. The aberrant epithelial cell interaction occurs within the basal layer at early precancerous lesions, which expands to the whole epithelial layer and strengthens along the cancer development and progression. Functional analysis revealed that the aberrant EFNB1-EPHB4 interaction is caused by overexpressed ΔNP63 due to TP53 mutation, the culprit in human ESCC tumorigenesis. Our results shed new light on the role of TP53-TP63/ΔNP63-EFNB1-EPHB4 axis in EMT and cell proliferation in epithelial cancer formation.

ABSTRACTThe effects of atmospheric pressure plasma jet (APPJ) treatment on the physicochemical and conformational properties of myofibrillar protein (MP) isolated from mandarin fish. The findings revealed that after exposing MP to APPJ for 0–12 s, there was a significant (P

Conventional model-driven methods are hard to handle large-scale power flow with multivariate uncertainty, variable topology, and massive real-time repetitive calculations. With the ability to deal with non-Euclidean graph-structured power system data, graph deep learning shows great potential in modern power flow calculation. However, general graph deep learning based power flow calculation has limited adaptability because of its sole mapping of node information and black-box attributes. In this paper, an edge graph attention network based power flow calculation (EGAT-PFC) model is proposed with improved adaptability for power flow analysis of complex system scenarios. First, the dual-model structure of the node model and edge model is constructed to realize a complete power flow mapping covering all information in power systems. Second, an improved learnable attention coefficient mechanism fusing node and edge features is proposed to ensure global information can be completely considered. Third, mechanisms of extended first-order neighborhood, dynamic normalization, and regularization-based loss function are designed to improve training performance. Finally, visualized interpretability is developed to show valuable information of vulnerable nodes and lines of power system operation. The numerical simulation verifies that EGAT-PFC has high accuracy, fast mapping, as well as excellent adaptability to variable topologies.

Ultrasound-assisted regulation of biomaterial properties has attracted increasing attention due to the unique reaction conditions induced by ultrasound cavitation. In this study, we explored the fabrication of wild tussah silk nanofiber membranes via ultrasound spray spinning from an ionic liquid system, characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), atomic force microscopy (AFM), water contact angle, cytocompatibility tests, and enzymatic degradation studies. We investigated the effects of ultrasound propagation in an ionic liquid on the morphology, structure, thermal and mechanical properties, surface hydrophilicity, biocompatibility, and biodegradability of the fabricated fibers. The results showed that as ultrasound treatment time increased from 0 to 60 min, the regenerated silk fiber diameter decreased by 0.97 μm and surface area increased by 30.44 μm2, enhancing the fiber surface smoothness and uniformity. Ultrasound also promoted the rearrangement of protein molecular chains and transformation of disordered protein structures into β-sheets, increasing the β-sheet content to 54.32 %, which significantly improved the materials’ thermal stability (with decomposition temperatures rising to 256.38 °C) and mechanical properties (elastic modulus reaching 0.75 GPa). In addition, hydrophilicity, cytocompatibility, and biodegradability of the fiber membranes all improved with longer ultrasound exposure, highlighting the potential of ultrasound technology in advancing the properties of natural biopolymers for applications in sustainable materials science and tissue regeneration.

Glioblastoma (GBM) is known for its aggressive nature and poor prognosis, with currently no effective treatment available. Research has shown that introducing fluorinated functional groups into different parts of natural product quinoline significantly affects its anti-tumor activity. Therefore, this study synthesized the trifluoromethyl quinoline derivative FKL296 to investigate its anti-tumor effect on GBM and reveal its mechanism of action. In vitro and in vivo studies have shown that FKL296 effectively inhibitd the growth of GBM and is relatively safe and low toxicity, whice also induced cell apoptosis and autophagy. Additionally, protein kinase profiling and molecular docking analyses have revealed a strong binding affinity between FKL296 and SGK1. Cellular thermal shift assay experiments have confirmed the targeting of SGK1 by FKL296 and its role in enhancing SGK1 stability. Bioinformatics analysis and pathway validation indicated that FKL296 targeted SGK1 and inhibited autophagy in tumor cells through the mTOR/FOXO3a signaling pathway. In summary, FKL296 may become a promising drug for the treatment of GBM.

Kuding tea (KT) is the general name of a set of bitter-tasting herbal tea made from varied original plant species. However, limited information was reported about the difference of bioactive constituents, heavy metals, and bioactivities among those original species. In the present study, comparison analyses among heavy metals, polysaccharides, phenolics, flavonoids, and saponins constituents, as well as the antioxidant and antidiabetic activities were performed through colorimetry, UPLC-QTOF-MS, enzymatic assay and molecular docking techniques on the six KT original plants mainly from the genus Ilex. Results showed that Cd contents in the four KT original plants other than Ilex pubescens (IP) and Ilex cornuta (IC) and heavy metal contents including Pb, Cu, As and Hg in the all six plants were lower than standard limit values. Furthermore, contents of carbohydrate in polysaccharides (470.06 and 548.51 mg GLE/g), total phenolics (33.84 and 48.85 mg GAE/g), flavonoids (30.86 and 109.97 mg RE/g), phenolic acids (49.68 and 61.48 mg CAE/g), flavonols (18.47 and 19.19 mg RE/g), flavanols (0.18 and 0.14 mg CE/g), saponins (90.81 and 97.33 mg GSE /g) in IP and Ligustrum japonicum (LJ), as well as their antioxidant activity levels (IC50 607.41–780.44, and 547.06–754.00 mg/L) were all significantly higher than those in other four KT original plants. Moreover, a total of 6 and 9 compounds were tentatively characterized from IP and LJ, respectively, and molecular docking and molecular dynamics simulation were further used to analysis the interaction between α-glucosidase and bioactive compounds in IP. At last, principal component, hierarchical cluster, and correlation analysis indicated that carbohydrate content of polysaccharides, total phenols, flavonoids and phenolic acids were the main influencing factors to antioxidant abilities. Overall, according to our systematic analysis, IP possessed the highest antioxidant and antidiabetic potentials, thus might be a better KT original plants from the genus Ilex for further development and utilization.

ABSTRACT: This study aimed to investigate the effects of dietary Bacillus velezensis KNF-209 (BV-KNF-209) on the growth performance, immunity, and gut health of broilers. A total of 540 one-day-old male Cobb-500 broilers were randomly divided into 5 groups of 6 replicates with 18 broilers per replicate. Dietary treatments were corn-soybean meal basal diets supplemented with 0, 50, 100, 200, and 400 mg/kg BV-KNF-209 (CON, BV 50, BV 100, BV 200, and BV 400 groups, respectively) for 42 d. Compared with the CON group, the average daily gains (ADG) at 0 to 42 d in the BV 100 and BV 200 groups were significantly increased (P < 0.01), and the feed-to-gain (F:G) ratios were significantly decreased at 0 to 21 d (P < 0.01) and 0 to 42 d (P < 0.05). The BV 200 and BV 400 groups had higher serum immunoglobulin M (IgM) levels at d 21 and 42 (P < 0.05). The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were significantly decreased in the BV 50, BV 100, and BV 200 groups at d 21 (P < 0.05), and serum IL-1β and IL-6 levels were also reduced in the BV 100 and BV 200 groups at d 42 (P < 0.05). Meanwhile, increased interleukin-10 (IL-10) levels in the jejunal and ileal mucosa at d 42 were observed in the BV 100, BV 200, and BV 400 groups (P < 0.05), while the IL-1β and IL-6 levels (P < 0.01) were decreased. The BV 200 and BV 400 groups showed significantly higher activities of lipase and trypsin (P < 0.05) in jejunal digesta as well as higher activities of amylase and trypsin (P < 0.01) in ileal digesta at d 42. The cecal acetic acid and propionic acid levels in the BV groups and lactic acid levels in the BV 50, BV 100, and BV 200 groups (P < 0.05) were significantly higher compared to those in the CON group. Overall, dietary BV-KNF-209 supplementation significantly improved broiler growth performance, an effect that may have been achieved by heightening immunity, increasing digestive enzyme activity, and raising intestinal short-chain fatty acids and lactic acid levels.

Abstract Objectives The recommended treatment for limited‐stage small‐cell lung cancer (LS‐SCLC) is a combination of thoracic radiotherapy (TRT) and etoposide plus cisplatin (EP) chemotherapy, typically administered over 4–6 cycles. Nonetheless, the optimal duration of chemotherapy is still not determined. This study aimed to compare the outcomes of patients with LS‐SCLC who received either 6 cycles or 4–5 cycles of EP chemotherapy combined with TRT. Materials and Methods In this retrospective analysis, we utilized data from our prior prospective trial to analyze the outcomes of 265 LS‐SCLC patients who received 4–6 courses of EP combined with concurrent accelerated hyperfractionated TRT between 2002 and 2017. Patients were categorized into two groups depending on their number of chemotherapy cycles: 6 or 4–5 cycles. To assess overall survival (OS) and progression‐free survival (PFS), we employed the Kaplan–Meier method after conducting propensity score matching (PSM). Results Among the 265 LS‐SCLC patients, 60 (22.6%) received 6 cycles of EP chemotherapy, while 205 (77.4%) underwent 4–5 cycles. Following PSM (53 patients for each group), the patients in the 6 cycles group exhibited a significant improvement in OS and PFS in comparison to those in the 4–5 cycles group [median OS: 29.8 months (95% confidence interval [CI], 23.6–53.1 months) vs. 22.7 months (95% CI, 20.8–29.1 months), respectively, p = 0.019; median PFS: 17.9 months (95% CI, 13.7–30.5 months) vs. 12.0 months (95% CI, 9.8–14.2 months), respectively, p = 0.006]. The two‐year and five‐year OS rates were 60.38% and 29.87% in the 6 cycles group, whereas 47.17% and 15.72% in the 4–5 cycles group, respectively. Conclusion Patients diagnosed with LS‐SCLC who were treated with EP regimen chemotherapy combined with TRT exhibited notably enhanced survival when administered 6 cycles of chemotherapy, as compared to those who underwent only 4–5 cycles.

Introduction:Ganoderma lucidum: (G. lucidum, Lingzhi) is a medicinal and edible homologous traditional Chinese medicine that is used to treat various diseases, including Alzheimer’s disease and mood disorders. We previously reported that the sporoderm-removed G. lucidum spore extract (RGLS) prevented learning and memory impairments in a rat model of sporadic Alzheimer’s disease (sAD), but the effect of RGLS on depression-like behaviors in this model and its underlying molecular mechanisms of action remain unclear.Method: The present study investigated protective effects of RGLS against intracerebroventricular streptozotocin (ICV-STZ)-induced depression in a rat model of sAD and its underlying mechanism. Effects of RGLS on depression- and anxiety-like behaviors in ICV-STZ rats were assessed in the forced swim test, sucrose preference test, novelty-suppressed feeding test, and open field test.Results: Behavioral tests demonstrated that RGLS (360 and 720 mg/kg) significantly ameliorated ICV-STZ-induced depression- and anxiety-like behaviors. Immunofluorescence, Western blot and enzyme-linked immunosorbent assay results further demonstrated that ICV-STZ rats exhibited microglia activation and neuroinflammatory response in the medial prefrontal cortex (mPFC), and RGLS treatment reversed these changes, reflected by the normalization of morphological changes in microglia and the expression of NF-κB, NLRP3, ASC, caspase-1 and proinflammatory cytokines. Golgi staining revealed that treatment with RGLS increased the density of mushroom spines in neurons. This increase was associated with elevated expression of brain-derived neurotrophic protein in the mPFC.Discussion: In a rat model of ICV-STZ-induced sAD, RGLS exhibits antidepressant-like effects, the mechanism of which may be related to suppression of the inflammatory response modulated by the NF-κB/NLRP3 pathway and enhancement of synaptic plasticity in the mPFC.

Introduction:Ganoderma lucidum (G. lucidum, Lingzhi) has long been listed as a premium tonic that can be used to improve restlessness, insomnia, and forgetfulness. We previously reported that a rat model of sporadic Alzheimer’s disease (sAD) that was induced by an intracerebroventricular injection of streptozotocin (ICV-STZ) showed significant learning and cognitive deficits and sleep disturbances. Treatment with a G. lucidum spore extract with the sporoderm removed (RGLS) prevented learning and memory impairments in sAD model rats.Method: The present study was conducted to further elucidate the preventive action of RGLS on sleep disturbances in sAD rats by EEG analysis, immunofluorescence staining, HPLC-MS/MS and Western blot.Results: Treatment with 720 mg/kg RGLS for 14 days significantly improved the reduction of total sleep time, rapid eye movement (REM) sleep time, and non-REM sleep time in sAD rats. The novelty recognition experiment further confirmed that RGLS prevented cognitive impairments in sAD rats. We also found that RGLS inhibited the nuclear factor-κB (NF-κB)/Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammatory pathway in the medial prefrontal cortex (mPFC) in sAD rats and ameliorated the lower activity of γ-aminobutyric acid (GABA)-ergic neurons in the parabrachial nucleus (PBN).Discussion: These results suggest that inhibiting the neuroinflammatory response in the mPFC may be a mechanism by which RGLS improves cognitive impairment. Additionally, improvements in PBN-GABAergic activity and the suppression of neuroinflammation in the mPFC in sAD rats might be a critical pathway to explain the preventive effects of RGLS on sleep disturbances in sAD.

Radiotherapy stands as a cornerstone in the treatment of numerous malignant tumors, including non-small cell lung cancer. However, the critical challenge of amplifying the tumoricidal effectiveness of radiotherapy while minimizing collateral damage to healthy tissues remains an area of significant research interest. Radiosensitizers, by methods such as amplifying DNA damage and fostering the creation of free radicals, play a pivotal role in enhancing the destructive impact of radiotherapy on tumors. Over recent decades, nano-dimensional radiosensitizers have emerged as a notable advancement. Their mechanisms include cell cycle arrest in the G2/M phase, combating tumor hypoxia, and others, thereby enhancing the efficacy of radiotherapy. This review delves into the evolving landscape of nanomaterials used for radiosensitization in non-small cell lung cancer. It provides insights into the current research progress and critically examines the challenges and future prospects within this burgeoning field.

Background Personalized blood pressure (BP) management for patients with acute ischemic stroke after successful endovascular thrombectomy lacks evidence. We aimed to investigate whether the deviation of BP from cerebral autoregulation limits is associated with worse outcomes. Methods and Results We determined autoregulation by measuring mean velocity index and calculated the percentage of time and the burden (defined as the time‐BP area) with BP outside the autoregulatory limits of each subject within 48 hours after endovascular thrombectomy. In total, 91 patients with large vessel occlusion stroke who had achieved successful recanalization were prospectively enrolled between May 2020 and February 2022. The burden with BP outside the autoregulatory limits was associated with poor outcome (modified Rankin Scale score 3–6) at 90 days (adjusted odds ratio, 1.28 [95% CI, 1.03–1.59]). The percentage of time with BP out of the autoregulatory limits was correlated with early neurological deterioration (National Institute of Health Stroke Scale scores increased ≥2 at 7 days) (adjusted odds ratio, 1.38 [95% CI, 1.04–1.83]). The burden of BP that decreased below the autoregulatory lower limit was associated with significant infarct growth (volume of infarct growth >11.6 mL) at 7 days (adjusted odds ratio, 1.21 [95% CI, 1.01–1.44]). The percentage of time that BP exceeded the autoregulatory upper limit was associated with symptomatic intracranial hemorrhage within 48 hours (adjusted odds ratio, 1.55 [95% CI, 1.02–2.34]). Conclusions Both the percentage of time and the burden of BP that deviates from the autoregulation‐preserved range are associated with unfavorable clinical outcomes. This study highlights the potential benefits of autoregulation‐guided BP management strategy after successful recanalization.

Background: The coexistence of autoimmune encephalitis (AE) with multiple neural auto-antibodies is of great clinical significance because overlying antibodies may cause superposition or variation of clinical syndrome, which increases the difficulty of diagnosis and treatment of the disease. To the best of our knowledge, the coexistence of anti-N-methyl d-aspartate Receptor (NMDAR) and anti-IgLON5 antibodies in AE has not been published previously. Case presentation: A 38-year-old female patient presented to our hospital due to headache and abnormal psychiatric behavior. Based on her clinical manifestations (psychiatric and behavioral abnormalities, involuntary limb movements, and sleep disorders) and laboratory assessment results (positive human leukocyte antigen (HLA)-DQB1*05:01 haplotype, anti-NMDAR, and anti-IgLON5 antibodies), she was diagnosed as AE with coexisting anti-NMDAR and anti-IgLON5 antibodies. After treatment with intravenous methylprednisolone and immunoglobulin, as well as plasmapheresis, her symptoms gradually improved with exception for the sleep disorders. Although oral prednisone acetate and mycophenolate mofetil were continued after discharge, her symptoms of sleep disorders did not improve at 6-month follow-up. Conclusion: This is the first case of AE co-existing with anti-NMDAR and anti-IgLON5 antibodies. Co-existence of neural auto-antibodies should be considered when patients present with overlapping or atypical symptoms. Special attention should be paid to the treatment of these patients as some anti-IgLON5 encephalitis patients may not benefit from immunotherapy treatment.

The microbial potential of Penicillium has received critical attention. The present research aimed to elucidate the efficacy of crude enzyme secreted from Penicillium oxalicum WX-209 in degrading citrus segments and evaluate the safety of the process. Results showed that citrus segment membranes gradually dissolved after treatment with the crude enzyme solution, indicating good degradation capability. No significant differences in body weight, food ingestion rate, hematology, blood biochemistry, and weight changes of different organs were found between the enzyme intake and control groups. Serial experiments showed that the crude enzyme had high biological safety. Moreover, the whole genome of P. oxalicum WX-209 was sequenced by PacBio and Illumina platforms. Twenty-five scaffolds were assembled to generate 36 Mbp size of genome sequence comprising 11 369 predicted genes modeled with a GC content of 48.33 %. A total of 592 genes were annotated to encode enzymes related to carbohydrates, and some degradation enzyme genes were identified in strain P. oxalicum WX-209. Data availability: The whole genome sequencing data in this study can be found in GenBank database of NCBI website with the accession number PRJNA 715321. The link: http://www.ncbi.nlm.nih.gov/bioproject/715321.

With the construction of new-type power system under the ”double carbon” target and the increasing diversification of the energy demand of the user side, the short-term load forecasting of power system is facing new challenges. In order to fully exploit the massive information contained in big data, this paper proposed a new short-term load forecasting method for new-type power system considering multiple factors, which based on Graph Convolutional Network (GCN) and Long Short-Term Memory network (LSTM). Spearman rank correlation coefficient was used to analyze the correlation between load and meteorological factors, and a quantitative model including meteorological factors, date factors and regional factors was established. Thus, GCN and LSTM were jointly used to extract the spatial and temporal characteristics of massive data respectively, and finally the short-term power load forecasting was achieved. The public data sets were used for performance verification compared with three comparison models, LSTM, CNN-LSTM and TCN-LSTM. The results show that the proposed method can make full use of the influence of multi-dimensional data, meanwhile improve the load prediction accuracy and training efficiency effectively.

Abstract Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, and its incidence has been increasing in recent years. Due to the insidious onset and strong local invasiveness of MPM, most patients are diagnosed in the late stage and early screening and treatment for high‐risk populations are crucial. The treatment of MPM mainly includes surgery, chemotherapy, and radiotherapy. Immunotherapy and electric field therapy have also been applied, leading to further improvements in patient survival. The Mesothelioma Group of the Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) developed a national consensus on the clinical diagnosis and treatment of MPM based on existing clinical research evidence and the opinions of national experts. This consensus aims to promote the homogenization and standardization of MPM diagnosis and treatment in China, covering epidemiology, diagnosis, treatment, and follow‐up.

When high-speed trains enter tunnels, an initial compression wave is generated. As the compression wave propagates at the local speed of sound to the tunnel exit, it radiates into the surrounding environment, forming micro-pressure waves (MPWs). MPWs create sonic booms, resulting in significant environmental issues. The magnitude of the micro-pressure waves is directly proportional to the pressure gradient of the compression wave at the tunnel exit. The nonlinear effects of the initial compression wave during propagation lead to a significant increase in pressure gradient. Therefore, the propagation characteristics of the initial compression wave during the tunnel are the crucial factor affecting the amplitude of MPWs. Based on the one-dimensional compressible unsteady non-isentropic flow model and the improved generalized Riemann variable characteristic method, this paper researched the propagation and evolution characteristics of an initial compression wave generated when 400 km/h high-speed trains enter tunnels with three portal shapes: (no tunnel entrance hood (no hood), an oblique, enlarged tunnel entrance hood (type A), an enlarged equal-section non-uniform opening hole tunnel entrance hood (type B)). The results show that when the initial compression wave propagates inside very long tunnels, the pressure gradient of the compression wave exhibits a trend of initially increasing and then decreasing with the increase in propagation distance. When the pressure gradient of the compression wave reaches its maximum value, the corresponding propagation distance is the steepening critical distance. For no tunnel entrance hoods, type A tunnel entrance hoods, and type B tunnel entrance hoods, the steepening critical distances are 5 km, 6 km, and 16 km, respectively. The steepening critical distance shortens with increasing train speed. Steady friction and unsteady friction effects mainly affect the pressure amplitude and pressure gradient during compression wave propagation, respectively. At lower ambient temperatures, the nonlinear effects in compression wave propagation are significantly enhanced. The mitigation effects of type A tunnel entrance hoods and type B tunnel entrance hoods on pressure gradient reduction are mainly concentrated within 4 km and 12 km, respectively. It is necessary to determine the optimal matching relationship between the tunnel entrance hood and tunnel length based on the characteristics of compression wave propagation to ensure their mitigating performance is maximized.

The application of intracerebroventricular injection of streptozotocin (ICV-STZ) is considered a useful animal model to mimic the onset and progression of sporadic Alzheimer’s disease (sAD). In rodents, on day 7 of the experiment, the animals exhibit depression-like behaviors. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme catalyzing the conversion of tryptophan (Trp) to kynurenine (Kyn), is closely related to depression and AD. The present study aimed to investigate the pathophysiological mechanisms of preliminary depression-like behaviors in ICV-STZ rats in two distinct cerebral regions of the medial prefrontal cortex, the prelimbic cortex (PrL) and infralimbic cortex (IL), both presumably involved in AD progression in this model, with a focus on IDO-related Kyn pathways. The results showed an increased Kyn/Trp ratio in both the PrL and IL of ICV-STZ rats, but, intriguingly, abnormalities in downstream metabolic pathways were different, being associated with distinct biological effects. In the PrL, the neuroprotective branch of the Kyn pathway was attenuated, as evidenced by a decrease in the kynurenic acid (KA) level and Kyn aminotransferase II (KAT II) expression, accompanied by astrocyte alterations, such as the decrease in glial fibrillary acidic protein (GFAP)-positive cells and increase in morphological damage. In the IL, the neurotoxicogenic branch of the Kyn pathway was enhanced, as evidenced by an increase in the 3-hydroxy-kynurenine (3-HK) level and kynurenine 3-monooxygenase (KMO) expression paralleled by the overactivation of microglia, reflected by an increase in ionized calcium-binding adaptor molecule 1 (Iba1)-positive cells and cytokines with morphological alterations. Synaptic plasticity was attenuated in both subregions. Additionally, microinjection of the selective IDO inhibitor 1-Methyl-DL-tryptophan (1-MT) in the PrL or IL alleviated depression-like behaviors by reversing these different abnormalities in the PrL and IL. These results suggest that the antidepressant-like effects linked to Trp metabolism changes induced by 1-MT in the PrL and IL occur through different pathways, specifically by enhancing the neuroprotective branch in the PrL and attenuating the neurotoxicogenic branch in the IL, involving distinct glial cells.

Interest in macropinocytosis has risen in recent years owing to its function in tumorigenesis, immune reaction, and viral infection. Cancer cells utilize macropinocytosis to acquire nutrients to support their uncontrolled proliferation and energy consumption. Macropinocytosis, a highly dynamic endocytic and vesicular process, is regulated by a series of cellular signaling pathways. The activation of small GTPases in conjunction with phosphoinositide signaling pivotally regulates the process of macropinocytosis. In this review, we summarize important findings about the regulation of macropinocytosis and provide information to increase our understanding of the regulatory mechanism underlying it.

Background: The data on immune checkpoint inhibitors (ICI) use in lung cancer individuals generally underrepresented in clinical trials are limited. We aimed to examine the ICI access, safety, and outcome in these populations using real-world data. Methods: Patients with lung cancer newly started on ICIs from 2018 to 2021 were included. Patient factors (age, sex, race, insurance, Charlson comorbidity index (CCI), Eastern Cooperative Oncology Group (ECOG) performance status, histories of autoimmune disease (AD), infection within 3 months before treatment, and brain metastasis) were collected and grouped. Associations of each patient factor with the time-to-treatment initiation (TTI) of ICIs and immune-related adverse events (irAEs) were examined via cumulative incidence analyses and Chi-squared tests, respectively. Log-rank tests and Cox models were used to assess association of patient factors with overall survival (OS). Results: Of 125 patients (median age:70 years (50–88), 68 (54.4 %) males), 9 (7.2 %) had Medicaid/uninsured, 44 (35.2 %) had ECOG ≥ 2, 101 (80.8 %) had CCI ≥ 3, 16 (12.8 %) had ADs, 14 (11.2 %) had infections, and 26 (20.8 %) had brain metastases. In newly diagnosed stage IV patients (N = 62), no difference in TTI was found by patient factors. Fifty irAEs occurred within 12 months and no differences in irAEs occurrence by patient factors. In advanced-stage group (N = 123), OS did not differ by patient factors, except for race (p = 0.045). Whites showed an inferior OS than non-Whites in multivariable regression. (Hazards ratio = 2.82 [1.01–7.87], p = 0.047). Conclusions: Previously poorly represented subgroups were shown to have no significant delays in ICI use, general tolerance, and comparable outcomes. This adds practical evidence to ICI use in clinically and/or socio-demographically marginalized populations.

Text-independent speaker verification (TI-SV) is a crucial task in speaker recognition, as it involves verifying an individual’s claimed identity from speech of arbitrary content without any human intervention. The target for TI-SV is to design a discriminative network to learn deep speaker embedding for speaker idiosyncrasy. In this paper, we propose a deep speaker embedding learning approach of a hybrid deep neural network (DNN) for TI-SV in FM broadcasting. Not only acoustic features are utilized, but also phoneme features are introduced as prior knowledge to collectively learn deep speaker embedding. The hybrid DNN consists of a convolutional neural network architecture for generating acoustic features and a multilayer perceptron architecture for extracting phoneme features sequentially, which represent significant pronunciation attributes. The extracted acoustic and phoneme features are concatenated to form deep embedding descriptors for speaker identity. The hybrid DNN demonstrates not only the complementarity between acoustic and phoneme features but also the temporality of phoneme features in a sequence. Our experiments show that the hybrid DNN outperforms existing methods and delivers a remarkable performance in FM broadcasting TI-SV.

BackgroundEarly-onset androgenetic alopecia (AGA) has been associated with various chronic conditions, including metabolic syndrome (MetS). Gaining a deep understanding of early-onset AGA may enable earlier intervention in individuals at high risks. This scoping review aims to explore the risk factors and etiology, associated conditions, and adverse effects on wellbeing in early-onset AGA.MethodsElectronic literature searches were conducted in MEDLINE, EMBASE and CENTRIAL. Eligible studies included case-control, cohort, cross-sectional, and meta-analysis studies. Selected studies needed to clearly define early-onset AGA cases or include only cases starting before the age of 40 and compare them with appropriate controls. The exclusion criteria comprised editorials, commentaries, case series, and non-systematic reviews, among others. Data extraction involved collecting study characteristics, methodologies, main outcomes, and findings. Descriptive tables were used to summarize key information and relevant variables when necessary.ResultsAmong the 65 eligible articles, 67.69% were case-control studies and 78.46% evaluated only male patients. "Early-onset" was defined as cases developing before the age of 30 years in 43.08% of the studies. The Hamilton-Norwood scale was the most frequently used method for evaluating the severity of alopecia in men (69.23%). Reported risk factors for early-onset AGA included a family history of AGA, cigarette smoking, unhealthy dietary habits, and a high body mass index. Early-onset AGA may also be associated with hormonal profiles, 5α-reductase enzyme activity, androgen receptor genes, and some susceptibility loci. Comorbidities investigated included MetS, cardiovascular disease, insulin resistance, dyslipidemia, and Parkinson's disease. Men with early-onset AGA may have reduced treatment efficacy with drug like rosuvastatin, metformin or lisinopril for dyslipidemia, prediabetes, or hypertension. Additionally, young men with AGA tended to suffer from psychological issues such as anxiety and low self-esteem compared to those without hair loss.ConclusionEarly-onset AGA is a complex condition with various risk factors and etiology, associated comorbidities, and potential implications for treatment response and psychological health.

Background. Based on PACIFIC trial, durvalumab as consolidation therapy following concurrent chemoradiotherapy (cCRT) has been a new standard treatment for unresectable stage III non-small cell lung cancer (NSCLC). In clinical applications, there are heterogeneous adjustments or novel strategies following specialized discussions in experienced multidisciplinary teams. This study retrospectively compared the efficacy and safety of different first-line treatments for unresectable stage III NSCLC. Methods. We retrospectively analyzed 397 patients who received first-line treatment for unresectable stage III NSCLC. Comparisons and statistical analyses of treatment were made in terms of efficacy and safety. Adverse events and responses were assessed using CTCAE v5.0 and RECIST v1.1. The progression-free survival (PFS) was estimated using the Kaplan–Meier method or the Cox survival regression model and compared using the log-rank test. Results. In wild-type driver genes group, the objective response rate (ORR), disease control rate (DCR), and median PFS (mPFS) were prolonged in the radiotherapy group compared to those in the nonradiotherapy group (ORR: 50.94% vs. 30.06%, p

The photoluminescence experiment was performed at 77 K on two types of heterostructures of In0.52Al0.48As/InP grown by molecular beam epitaxy. One type has the so-called direct interface formed with In0.52Al0.48As grown on the InP (100) substrate, and another is a double heterostructure type, i.e., InP/In0.52Al0.48As/InP, including the inverse interface formed with the InP cap. The thickness of both the as-grown InAlAs and InP layers is 2 µm. Under the excitation of 852 nm semiconductor laser, a single peak at 1.198 eV (P0) was observed for the direct interface whereas the inverse interface showed two peaks at 1.240 eV (P1) and 1.117 eV (P2). However, P2 manifests differently from P1 with two interesting features. First, it disappears when the excitation was replaced with the 532 nm laser. Second, when the cap layer of InP/In0.52Al0.48As/InP is thinned to 200 nm, P2 displays a large blueshift effect with the increase in laser intensity, but the extent of blueshift drops when the excitation is increased further into a higher power range. The phenomenon of P2 was attributed to the interface excitation-induced interplay between the luminescence with a carrier localization effect and that caused by the recombination of 2-dimensional electrons with the light-injected holes in the potential well at the interface.

The Beishan orogen, a significant component of the southern Altaids, presents an opportunity for investigating the intracontinental deformation and exhumation history of the Altaids during the Mesozoic era. Although previous studies indicated that the Beishan orogen has experienced multiple reactivation since the late Mesozoic, the precise extent of these events remains poorly constrained. Here, we provide a comprehensive synthesis of field observations and apatite fission track (AFT) thermochronological dating throughout the Beishan orogen. Detailed field observations confirmed four major E-W trending thrusts in our study area. Based on the youngest truncated strata associated with the thrusts and previous dating results from neighboring regions, we propose that these thrust sheets likely developed in the late Middle Jurassic. AFT dating results from seven pre-Mesozoic granitoid samples and associated with thermal history modeling demonstrate that the Beishan orogen experienced a rapid basement cooling during the mid-Cretaceous (~115–80 Ma). Moreover, a compilation of previously published and newly gained AFT data reveals a comparable mid-Cretaceous cooling event in other parts of Central Asia, such as Qilian Shan, Eastern Tianshan, and Altai-Sayan. This observation suggests that the mid-Cretaceous cooling event is more likely to be regional rather than localized. This mid-Cretaceous cooling pulse is interpreted as a tectonic exhumation controlled by boundary faults and related to the rotation of the Junggar and Tarim basins. These processes are linked to distant plate-margin events along the Eurasian continent.

BackgroundGitelman Syndrome (GS) patients frequently exhibit disrupted glucose metabolism, attributed to hypokalemia, hypomagnesemia and heightened aldosterone. This study delved into the genetic underpinnings linked to insulin resistance and diabetes in a GS patient, contextualized within his family history.MethodsThe hydrochlorothiazide and furosemide loading test were performed to ascertain the presence of GS. Oral glucose tolerance test (OGTT) evaluated glucose metabolism and insulin sensitivity. Whole-exome sequencing, validated by Sanger sequencing, was employed to confirm gene mutations, which were then tracked among the patient’s relatives.ResultsSymptoms and laboratory examination confirmed the clinical diagnosis of GS. Comprehensive whole-exome sequencing, augmented by Sanger sequencing validation, revealed a compound heterozygous mutation within the SLC12A3 gene (c.1108G>C in exon 9, c.676G>A in exon 5 and c.2398G>A in exon 20) in the patient. The OGTT affirmed diabetes and heightened insulin resistance, distinct from previous patients with GS we evaluated. Further genetic analysis identified a missense heterozygous mutation (c.97C>G in exon 1) within the PDX1 gene, inherited from the patient’s diabetic mother without GS. Furthermore, the patient’s brother, with impaired glucose tolerance but regular potassium levels, also bore this mutation, hinting at additional impacts of the PDX1 gene mutation on glucose metabolism regulation beyond the known impacts of GS.ConclusionThis study unveils unprecedented compound heterozygous mutations in the SLC12A3 and PDX1 genes in a GS patient. These findings illuminate the potential complex genetic factors influencing glucose metabolism disruptions in GS.Take-home messageThis research uncovers a novel combination of SLC12A3 and PDX1 gene mutations in a Gitelman Syndrome patient, revealing intricate genetic factors that potentially disrupt glucose metabolism and shedding light on familial diabetes links.

Objective As monotherapy such as topotecan has reached a plateau of effectiveness, new second-line treatments based on experience have been used in clinical application. This study compared the efficacy and safety of different second-line treatments for advanced small-cell lung cancer (SCLC). Methods A total of 380 patients with advanced SCLC were screened selectively in the retrospective study. Adverse events and patient responses were assessed using Common Terminology Criteria for Adverse Events v5.0 and Response Evaluation Criteria for Solid Tumors v1.1. The progression-free survival (PFS) was estimated using the Kaplan-Meier method or Cox survival regression model and compared using the log-rank test. Results In the platinum-resistant group, disease control rate (DCR) and median PFS (mPFS) were prolonged in the combination group versus single-agent group (DCR: 49.24% vs 24.39%, P = .004; mPFS: 3.73 vs 1.90 months, P