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In order to study the influence of temperature on the gas seepage law in loose coal bodies in goaf, gas seepage characteristics experiments were conducted on three types of coal samples, namely anthracite, bituminous coal, and lignite, under different temperature conditions using a self-developed loose coal temperature seepage comprehensive experimental platform, and COMSOL Multiphysics was used to simulate the gas seepage process through bituminous coal under constant temperature and continuous heating conditions. By studying the gas seepage law when there is a local heat source in the loose coal body in the goaf, a temperature based on gas seepage model for the loose coal body was established. Under constant temperature conditions ranging from 30 ℃ to 80 ℃, when air passes through loose and broken anthracite, bituminous coal, and lignite at a speed of less than 1.0 cm/s, it follows the linear Darcy flow law, and the pressure gradient gradually increases with the increase of specific flow rate; the permeability of coal decreases with increasing temperature, and the permeability changes of different coal samples vary with increasing temperature, and brown coal>bituminous coal>anthracite; as the temperature increases, the temperature distribution and permeability distribution inside the coal pillar can be approximated as an “ellipsoidal shell” near the gas outlet.

In response to the problem of blocked escape routes and difficulty in determining the location of trapped personnel caused by mining disasters and accidents, based on the principles and characteristics of ultra wideband (UWB) radar life information detection and position detection, combined with existing UWB radar detection technology, a UWB radar architecture suitable for borehole detection is proposed, key technical parameters are clarified, and a UWB radar life information detector is developed; we conducted UWB radar detection experiments under different detection distances, positions, target numbers, and weak body movements, and obtained detection spectrum features under three conditions. The experimental results show that the UWB radar life information detector can penetrate a 0.5 m brick wall and accurately locate personnel spatial information in complex terrain after disaster deformation. It can observe small-scale movements of personnel within a range of 4.0 m from radar echoes; when multiple human targets are within the same range of the radar transmitting and receiving antennas, and there are differences in their radial relative positions from the radar, the number of human targets can be determined based on the echo spectrum.

Abstract Background In evolutionary biology, identifying and quantifying inter-lineage genome size variation and elucidating the underlying causes of that variation have long been goals. Repetitive elements (REs) have been proposed and confirmed as being among the most important contributors to genome size variation. However, the evolutionary implications of genome size variation and RE dynamics are not well understood. Results A total of 35 Ensifera insects were collected from different areas in China, including nine species of crickets and 26 species of katydids. The genome sizes of seven species were then determined using flow cytometry. The RepeatExplorer2 pipeline was employed to retrieve the repeated sequences for each species, based on low-coverage (0.1 X) high-throughput Illumina unassembled short reads. The genome sizes of the 35 Ensifera insects exhibited a considerable degree of variation, ranging from 1.00 to 18.34 pg. This variation was more than 18-fold. Similarly, the RE abundances exhibited considerable variation, ranging from 13.66 to 61.16%. In addition, the Tettigonioidea had larger genomes and contained significantly more REs than did the Grylloidea genomes. Analysis of the correlation between RE abundance and the genome size of 35 Ensifera insects revealed that the abundance of REs, transposable elements (TEs), long terminal repeats (LTRs), and long interspersed nuclear elements (LINEs) are significantly correlated with genome size. Notably, there is an inflection point in this correlation, where species with increasingly large genomes (e.g., > 5–10 pg) have repeats that contribute less to genome expansion than expected. Furthermore, this study revealed contrasting evolutionary directions between the Tettigonioidea and Grylloidea clades in terms of the expansion of REs. Tettigonioidea species exhibit a gradual increase in ancestral genome size and RE abundance as they diverge, while Grylloidea species experience sustained genome contraction. Conclusions This study reveals extensive variation in genome size and RE abundance in Ensifera insects, with distinct evolutionary patterns across two major groups, Tettigonioidea and Grylloidea. This provides valuable insights into the variation in genome size and RE abundance in Ensifera insects, offering a comprehensive understanding of their evolutionary history.

Abstract D-dimer is a biomarker of coagulation and fibrinolytic system activation in response to the hypercoagulable state of the body. The research aimed to analyze the value of D-dimer in the prognosis of patients with dilated cardiomyopathy (DCM). Patients admitted to our center for the first time with DCM were enrolled consecutively. The clinical characteristics variables were obtained from the electronic medical record system, and the prognostic information was obtained using telephone return visits and a review of repeated hospitalization records. Univariate and multivariate Cox regression was used to explore the association of D-dimer with all-cause mortality. Smooth curve fitting, threshold saturation effect analysis, and subgroup analysis were performed. Ultimately, 534 patients were included. After a follow-up of the enrolled patients, 485 patients obtained prognostic information, of which 159 died from all causes, and the main cause of death was heart failure (89/159), the sudden death accounted for about 17%. The independent positive association between D-dimer and all-cause mortality remained unchanged in both unadjusted and adjusted Cox regression models. In the fully adjusted model, each standard deviation increase in D-dimer was associated with a 14% increase in all-cause mortality (HR = 1.14; 95% CI: 1.02 ~ 1.27; P

Horticultural products such as fruits, vegetables, and tea offer a range of important nutrients such as protein, carbohydrates, vitamins and lipids. However, the present yield and quality do not meet the requirements of the rapid population growth associated with global climate change, the decline in horticultural practitioners, poor automation, and epidemic diseases such as COVID-19. In this context, smart horticulture is expected to greatly improve the land output rates, resource-use efficiency, and productivity, all of which should facilitate the sustainable development of the horticulture industry. Emerging technologies, such as artificial intelligence, big data, the Internet of Things, and cloud computing, play an important role. This paper reviews past developments and current challenges, offering future perspectives for horticultural chain management. We expect that the horticulture industry would benefit from integration with smart technologies. This requires the use of novel solutions to build a new advanced system encompassing smart breeding, smart cultivation, smart transportation, and smart sales. Finally, a new development approach combining precise perception, smart operation, and smart control should be instituted in the horticulture industry. Within 30 years, we expect that the industry will embrace mechanical, automatic, and informational production to transform into a smart industry.

Objective: Osteoclast (OC) over-activation is an important cause of bone loss that is strongly correlated with inflammation. Although the CD163/TWEAK/Fn14 axis has been implicated in several inflammatory pathologies, its contributions to inflammatory bone loss remain poorly understood. This study aimed to evaluate the interaction of the CD163/TWEAK/Fn14 axis with OC in inflammatory bone loss. Methods: To assess the role of CD163 in bone homeostasis, we characterized the bone phenotypes of CD163-deficient mice and their wild-type littermates. CD163 and TWEAK levels were evaluated in the bone marrow of mice with LPS-induced bone loss and individuals with rheumatoid arthritis (RA). Bone mass changes were assessed using uCT and histology following supplementation with recombinant mouse CD163 protein (rCD163) or blockade of TWEAK/Fn14 signaling in CD163-deficient mice and mice with LPS-induced bone loss. The impact of CD163/TWEAK on OC differentiation and bone resorption capacity was analyzed in vitro. Results: CD163 deficiency caused decreased bone mass and increased OC abundance. Lower CD163 expression and higher TWEAK expression were observed in the bone marrow of mice with LPS-induced bone loss and individuals with RA. TWEAK, mainly derived from CD68+ macrophages, was responsible for bone loss, and supplementing rCD163 or blocking TWEAK/Fn14 signaling contributed to rescue bone loss. TWEAK/Fn14 synergistically promoted RANKL-dependent OC differentiation and bone resorption capability through downstream mitogen-activated protein kinases (MAPK) signaling, while the pro-osteoclastic effect of TWEAK was suppressed by CD163. Conclusion: Our findings suggest that the CD163/TWEAK/Fn14 axis is a potential therapeutic target for inflammatory bone loss by regulating osteoclastogenesis.

Abstract Calcium (Ca) is an essential mineral nutrient and plays a crucial signaling role in all living organisms. Increasing Ca content in staple foods such as rice is vital for improving Ca nutrition of humans. Here we map a quantitative trait locus that controls Ca concentration in rice grains and identify the causal gene as GCSC1 (Grain Ca and Sr Concentrations 1), which encodes a chloroplast vesicle localized homo-oligomeric protein. GCSC1 exhibits Ca2+ transport activity in heterologous assays in yeast and Xenopus laevis oocytes and is involved in the efflux of Ca2+ from the chloroplast to the cytosol. Knockout of GCSC1 results in increased chloroplast Ca concentration, lower stomatal conductance in leaves and enhanced Ca allocation to grains. Natural variation in grain Ca concentration is attributed to the variable expression of GCSC1 resulting from its promoter sequence variation. Our study identifies a chloroplast localized heavy metal-associated domain containing protein that regulates chloroplast Ca2+ efflux and provides a way to biofortify Ca in rice to benefit human nutrition.

Abstract Background Nephroureterectomy with bladder cuff excision is the standard treatment for high-risk upper urinary tract urothelial carcinoma (UTUC). The role of minimally invasive surgery in treating locally advanced UTUC remains controversial. This study aimed to compare the outcomes of open, laparoscopic, and robotic surgeries for managing locally advanced UTUC. Methods We retrospectively reviewed 705 patients with locally advanced UTUC from multiple institutions throughout Taiwan. Perioperative outcomes and oncological outcomes, such as cancer-specific survival, overall survival, disease-free survival and bladder-free survival, were compared between the open, laparoscopic and robotic groups. Results The minimally invasive group had better overall and cancer-specific survival (CSS) rates. The 2-year CSS rates of the open, laparoscopic and robotic groups were 71%, 83%, and 77% respectively (p

Abstract Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.

Abstract The variability of renewable energy within microgrids (MGs) necessitates the smoothing of power fluctuations through the effective scheduling of internal power equipment. Otherwise, significant power variations on the tie‐line connecting the MG to the main power grid could occur. This study introduces an innovative scheduling strategy that utilizes a data‐driven approach, employing a deep reinforcement learning algorithm to achieve this smoothing effect. The strategy prioritizes the scheduling of MG's internal power devices, taking into account the stochastic charging patterns of electric vehicles. The scheduling optimization model is initially described as a Markov decision process with the goal of minimizing power fluctuations on the interconnection lines and operational costs of the MG. Subsequently, after preprocessing the historical operational data of the MG, an enhanced scheduling strategy is developed through a neural network learning process. Finally, the results from four scheduling scenarios demonstrate the significant impact of the proposed strategy. Comparisons of reward curves before and after data preprocessing underscore its importance. In contrast to optimization results from deep deterministic policy gradient, soft actor‐critic, and particle swarm optimization algorithms, the superiority of the deep deterministic policy gradient algorithm with the addition of a priority experience replay mechanism is highlighted.

Exbucklandia longipetala and Exbucklandia populnea are two evergreen trees of the genus Exbucklandia in the family Hamamelidaceae. In this study, the complete chloroplast genomes of E. longipetala and E. populnea were sequenced, assembled, and annotated. The total lengths of the chloroplast genomes were 160,723 bp and 160,744 bp, respectively, and both had a GC content of 38.1%. The complete chloroplast genomes of these two species had typical quadripartite structures: LSC region (88,972 bp and 88,989 bp), SSC region (18,907 bp and 18,911 bp) and a pair of inverted repeats both of 26,422 bp. Both species contained 114 unique genes, including 80 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. Phylogenetic analysis indicated that E. longipetala and E. populnea are sister species to each other. Our results provide useful genetic resources for further studies on the origin and evolution of Hamamelidaceae.

The determination of rock’s Capillary water absorption (CWA) requires extensive and complex empirical investigations, while forecasting algorithms could reduce the cost and time required. To achieve this goal, various rock records were collected from different rock types. For the forecasting model, two techniques named ANFIS and SVR were developed, with the model parameters determined using the Imperialist Competitive Algorithm (ICA). The proposed hybrid ICA-SVR and ICA-ANFIS models demonstrate exceptional performance in predicting CWA, with R^2 values exceeding 0.9851 and 0.9586 for the testing and training stages, respectively, indicating a strong correlation between predicted and measured CWA values. Considering all computed metrics, the SVR model optimized with ICA yielded better results than the ICA-ANFIS model in both testing and training stages. For example, the R^2 values for the ICA-SVR model were 0.9758 and 0.9747 for the testing and training datasets, respectively, with VAF values of 0.9889 and 0.9859 . The ICA-ANFIS model also produced acceptable results, though its performance was slightly weaker than the SVR model. Compared to a previous study, the proposed models show a significant improvement in efficiency, with the R^2 value increasing from 0.708 to 0.9889 . In summary, the enhanced ICA-SVR model can be considered a reliable and powerful tool for accurately determining the optimal values of the system’s key variables.

Despite the promising prospects of nanoparticles in oral drug delivery, the process of oral administration involves a complex transportation pathway that includes cellular uptake, intracellular trafficking, and exocytosis by intestinal epithelial cells, which are necessary steps for nanoparticles to enter the bloodstream and exert therapeutic effects. Current researchers have identified several crucial factors that regulate the interaction between nanoparticles and intestinal epithelial cells, including surface properties such as ligand modification, surface charge, hydrophilicity/hydrophobicity, intestinal protein corona formation, as well as holistic properties like particle size, shape, and rigidity. Understanding these properties is essential for enhancing transepithelial transport efficiency and designing effective oral drug delivery systems. Therefore, this review provides a comprehensive overview of the surface and holistic properties that influence the transepithelial transport of nanoparticles, elucidating the underlying principles governing their impact on transepithelial transport. The review also outlines the chosen of parameters to be considered for the subsequent design of oral drug delivery systems.

Abstract Background Zhiguo ethnic groups, commonly known as “the directly-entering-socialism ethnic groups”, represent Chinese ethnic minorities who have undergone a unique social development trajectory by transforming directly from primitive societies to the socialist stage. In recent decades, significant lifestyle transformations have occurred among Zhiguo ethnic groups. Understanding their health lifestyles can play a strategic role in China’s pursuit of universal health coverage. This study aims to examine patterns of health-related lifestyle among Zhiguo ethnic groups and explore whether sociodemographic features and specific indicators related to health status are associated with particular classes. Methods A cross-sectional study was conducted in Yunnan Province, China, from July to December 2022. Stratified random sampling method was employed to recruit residents belonging to six Zhiguo ethnic groups aged between 15 and 64. Latent class analysis was performed to identify clusters of health-related behaviors within each ethnic group. Logistic regression was utilized to determine the predictors of health lifestyles. Results A total of 1,588 individuals from the Zhiguo ethnic groups participated in this study. Three latent classes representing prevalent health lifestyles among the Zhiguo ethnic groups were identified: “unhealthy lifestyle” (31.80%), “mixed lifestyle” (57.37%), and “healthy lifestyle” (10.83%). In the overall population, individuals belonging to the “healthy lifestyle” group exhibited a higher likelihood of being non-farmers (OR: 2.300, 95% CI: 1.347–3.927), women (OR: 21.459, 95% CI: 13.678–33.667), married individuals (OR: 1.897, 95% CI: 1.146–3.138), and those residing within a walking distance of less than 15 min from the nearest health facility (OR: 2.133, 95% CI: 1.415–3.215). Conversely, individuals in the age cohorts of 30–39 years (OR: 0.277, 95% CI: 0.137–0.558) and 40–49 years (OR: 0.471, 95% CI: 0.232–0.958) showed a decreased likelihood of adopting a healthy lifestyle. Conclusions A considerable proportion of the Zhiguo ethnic groups have not adopted healthy lifestyles. Targeted interventions aimed at improving health outcomes within these communities should prioritize addressing the clustering of unfavorable health behaviors, with particular emphasis on single male farmers aged 30–49, and expanding healthcare coverage for individuals residing more than 15 min away from accessible facilities.

Background: High-dose dual therapy (HDDT) using proton-pump inhibitors (PPI) and amoxicillin attracted attention for its simplicity and lower adverse event profile. Besides, vonoprazan is not available worldwide. This real-world study aims to compare the efficacy of esomeprazole-based and rabeprazole-based HDDT regimens and to identify clinical factors influencing outcomes. Methods: A retrospective study enrolled 346 Helicobacter pylori-infected naïve patients from January 2016 to August 2023. Patients were assigned to either a 14-day esomeprazole-based HDDT (EA-14; esomeprazole 40 mg t.i.d. and amoxicillin 750 mg q.i.d. for 14 days, n = 173) or a 14-day rabeprazole-based HDDT (RA-14; rabeprazole 20 mg and amoxicillin 750 mg q.i.d. for 14 days, n = 173). Results: Five patients from the EA-14 group and 10 from the RA-14 group were lost to follow-up, resulting in 168 and 163 patients for the per-protocol (PP) analysis, respectively. Eradication rates for the EA-14 and RA-14 groups were 90.2% and 80.9% (P = 0.014) in intention-to-treat (ITT) analysis; and 92.9% and 85.9% (P = 0.039) in PP analysis. Adverse event rates were similar between the two groups (11.9% vs 11.7%, P = 0.944). In multiple logistic regression analysis, age≧60 was associated with eradication failure (P = 0.046) and a trend of significance for smoking (P = 0.060) in the EA-14 group but not in the RA-14 group. A trend of significance was also observed for eradication regimens (EA-14 vs RA-14) (P = 0.071).The antibiotic resistance rates were amoxicillin (2.3%), clarithromycin (14.7%), metronidazole (40.3%), and dual resistance to clarithromycin and metronidazole (7.0%). Conclusions: Esomeprazole-based HDDT achieved over 90% eradication rates but rabeprazole-based HDDT, which failed.

Abstract Patients with end stage renal disease (ESRD) are at high risk of developing upper tract urothelial carcinoma (UTUC). Due to high recurrence rate of UTUC in contralateral kidney and ureter, and high risk of complications related to surgery and anesthesia, whether it’s necessary to remove both kineys and ureters at one time remains in debate. We utilized Taiwanese UTUC Registry Database to valuate the difference of oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving surgical resection. Patients with ESRD and UTUC were divided into three groups, unilateral UTUC, previous history of unilateral UTUC with metachronous contralateral UTUC, and concurrent bilatetral UTUC. Oncological outcomes, perioperative complications, and length of hospital stays were investiaged. We found that there is no diffence of oncological outcomes including overall survival, cancer specific survival, disease free survival and bladder recurrence free survival between these three groups. Complication rate and length of hospital stay are similar. Adverse oncological features such as advanced tumor stage, lymph node involvement, lymphovascular invasion, and positive surgical margin would negatively affect oncological outcomes.

Abstract Background Studies have shown that Chinese Clinicians and nurses have positive attitudes toward ACP, but no local tools exist to assess their need for ACP knowledge and skills training. resulting in their inability to initiate ACP conversations as well as poor end-of-life care for patients. Therefore, this study aims to assess the needs of Chinese Clinicians and nurses for ACP knowledge and skills training and assess the validity and reliability of a questionnaire on the Training Needs for Advance Care Planning (TNACP) scale. Methods From October to November 2021, 170 clinicians and nurses were pre-surveyed using a preliminary draft of the questionnaire. The responses were screened using item analysis, Cronbach’s alpha coefficient, and the intraclass correlation coefficient (ICC) to describe the internal consistency and stability of the questionnaire. The Content validity index (CVI), Exploratory factor analysis (EFA) and Confirmatory factor analysis (CFA) were used to test the validity of the questionnaire. Results After independent samples t-test analysis, Except for the entry “A2”, the critical ratio between the two groups of the remaining 23 items was statistically significant (p 0.40). The results of confirmatory factor analysis showed that the Training Needs for Advance Care Planning (TNACP) scale model fit well(X2/df = 2.504, RMSEA = 0.092, GFI = 0.809, AGFI = 0.745, CFI = 0.931, IFI = 0.932, TLI = 0.916); the Cronbach’s α = 0.888 for the total questionnaire, and the three dimensions of Cronbach’s α were 0.729 to 0.959; and the ICC for the overall scores between the test-retest evaluations was 0.884 (p

Abstract Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-β1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-β1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.

Abstract Background Breast cancer has become a major public health problem in the current society, and its incidence rate ranks the first among Chinese female malignant tumors. This paper once again confirmed the efficacy of lncRNA in tumor regulation by introducing the mechanism of the diagnosis of breast cancer by the MIR497HG/miR-16-5p axis. Methods The abnormal expression of MIR497HG in breast cancer was determined by RT-qPCR method, and the correlation between MIR497HG expression and clinicopathological characteristics of breast cancer patients was analyzed via Chi-square test. To understand the diagnostic potential of MIR497HG in breast cancer by drawing the receiver operating characteristic curve (ROC). The overexpressed MIR497HG (pcDNA3.1-MIR497HG) was designed and constructed to explore the regulation of elevated MIR497HG on biological function of BT549 and Hs 578T cells through Transwell assays. Additionally, the luciferase gene reporter assay and Pearson analysis evaluated the targeting relationship of MIR497HG to miR-16-5p. Results MIR497HG was decreased in breast cancer and had high diagnostic function, while elevated MIR497HG inhibited the migration and invasion of BT549 and Hs 578T cells. In terms of functional mechanism, miR-16-5p was the target of MIR497HG, and MIR497HG reversely regulated the miR-16-5p. miR-16-5p mimic reversed the effects of upregulated MIR497HG on cell biological function. Conclusions In general, MIR497HG was decreased in breast cancer, and the MIR497HG/miR-16-5p axis regulated breast cancer tumorigenesis, providing effective insights for the diagnosis of patients.

Purpose: Active surveillance (AS) is one of the management options for patients with low-risk and select intermediate-risk prostate cancer (PC). However, factors predicting disease reclassification and conversion to active treatment from a large population of pure Asian cohorts regarding AS are less evaluated. This study investigated the intermediate-term outcomes of patients with localized PC undergoing AS. Materials and Methods: This cohort study enrolled consecutive men with localized non-high-risk PC diagnosed in Taiwan between June 2012 and Jan 2023. The study endpoints were disease reclassification (either pathological or radiographic progression) and conversion to active treatment. The factors predicting endpoints were evaluated using the Cox proportional hazards model. Results: A total of 405 patients (median age: 67.2 years) were consecutively enrolled and followed up with a median of 64.6 months. Based on the National Comprehensive Cancer Network (NCCN) risk grouping, 70 (17.3%), 164 (40.5%), 140 (34.6%), and 31 (7.7%) patients were classified as very low-risk, low-risk, favorable-intermediate risk, and unfavorable intermediate-risk PC, respectively. The 5-year reclassification rates were 24.8%, 27.0%, 18.6%, and 25.3%, respectively. The 5-year conversion rates were 20.4%, 28.8%, 43.6%, and 37.8%, respectively. A prostate-specific antigen density (PSAD) of ≥0.15 ng/mL2 predicted reclassification (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.17–2.88) and conversion (HR 1.56, 95% CI 1.05–2.31). A maximal percentage of cancer in positive cores (MPCPC) of ≥15% predicted conversion (15% to

Abstract In order to improve the driving ability of the explosion wave simulation equipment, reduce the erosion effect of condensed explosives on the explosion wave simulation equipment, improve the safety of the test process, and make better use of the meteorological detonation driving method, it is necessary to optimize the source of the shock wave load in the driving section. Based on the finite volume method of FLACS, a methane detonation driving model corresponding to the test is established to explore the feasibility of using methane as an explosion source to test the structure against explosion shock wave. A methane detonation drive test was carried out to verify the accuracy of the numerical model. Finally, an engineering model for attenuation of shock wave overpressure peak value in pipeline is established by dimensional analysis, and the model coefficient is determined by numerical simulation and test data. The results show that the blast pressure is the highest when the methane volume ratio reaches 9.5 vol% in the methane-air mixture. Simply increasing oxygen content has little effect on the peak overpressure and positive pressure duration of shock wave. In the pure oxygen environment, the detonation effect can be achieved when the volume ratio of methane to oxygen is 1:2, and the incident pressure of the shock wave is proportional to the volume of the gas cloud. When the gas cloud volume is constant, a reasonable selection of methane-oxygen mixture ratio can achieve a better detonation effect, which can effectively increase the peak overpressure of the shock wave in the test section. The research results can provide technical reference for the development of new explosion wave simulation equipment.

Abstract The interaction between glioblastoma cells and glioblastoma-associated macrophages (GAMs) influences the immunosuppressive tumor microenvironment, leading to ineffective immunotherapies. We hypothesized that disrupting the communication between tumors and macrophages would enhance the efficacy of immunotherapies. Transcriptomic analysis of recurrent glioblastoma specimens indicated an enhanced neuroinflammatory pathway, with CXCL12 emerging as the top-ranked gene in secretory molecules. Single-cell transcriptome profiling of naïve glioblastoma specimens revealed CXCL12 expression in tumor and myeloid clusters. An analysis of public glioblastoma datasets has confirmed the association of CXCL12 with disease and PD-L1 expression. In vitro studies have demonstrated that exogenous CXCL12 induces pro-tumorigenic characteristics in macrophage-like cells and upregulated PD-L1 expression through NF-κB signaling. We identified CXCR7, an atypical receptor for CXCL12 predominantly present in tumor cells, as a negative regulator of CXCL12 expression by interfering with extracellular signal-regulated kinase activation. CXCR7 knockdown in a glioblastoma mouse model resulted in worse survival outcomes, increased PD-L1 expression in GAMs, and reduced CD8+ T-cell infiltration compared with the control group. Ex vivo T-cell experiments demonstrated enhanced cytotoxicity against tumor cells with a selective CXCR7 agonist, VUF11207, reversing GAM-induced immunosuppression in a glioblastoma cell-macrophage-T-cell co-culture system. Notably, VUF11207 prolonged survival and potentiated the anti-tumor effect of the anti-PD-L1 antibody in glioblastoma-bearing mice. This effect was mitigated by an anti-CD8β antibody, indicating the synergistic effect of VUF11207. In conclusion, CXCL12 conferred immunosuppression mediated by pro-tumorigenic and PD-L1-expressing GAMs in glioblastoma. Targeted activation of glioblastoma-derived CXCR7 inhibits CXCL12, thereby eliciting anti-tumor immunity and enhancing the efficacy of anti-PD-L1 antibodies.

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

Background: This study aimed to investigate the influence of immunonutritional factors on treatment-related toxicities and survival outcomes in patients with cervical cancer undergoing definitive radiochemotherapy. Methods: Patients with cervical cancer who received curative radiochemotherapy between 2016 and 2021 were retrospectively investigated. Pretreatment prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were measured. Survival outcomes, acute and late toxicities were evaluated. Results: Among the 138 patients, those with larger tumor diameters had significantly lower pre-treatment PNI (p = 0.005). Pre-treatment immunonutritional factors were predictive of clinical survival, whereas post-treatment factors did not correlate with prognosis. Patients with low pre-treatment PNI (2.4) had shorter progression-free survival (PFS, HR: 1.86, p = 0.045 for PNI; HR: 3.15, p = 0.002 for NLR) and overall survival (OS, HR: 1.80, p = 0.048 for PNI; HR: 3.83, p = 0.015 for NLR). High pre-treatment NLR was associated with an increased risk of acute diarrhea (p = 0.049) and late severe toxicities (p = 0.046). Combined analysis revealed that pre-treatment good nutritional status and low systemic inflammation were linked to longer PFS (p = 0.007) and OS (p = 0.002), and poor nutritional status and substantial systemic inflammation were associated with higher rates of late severe toxicities (p = 0.036), with higher prognostic value in advanced stage patients. Conclusion: Pretreatment immunonutritional measures serve as quantitative biomarkers for predicting survivals and treatment toxicities in patients with cervical cancer treated with definitive radiochemotherapy.

Purpose:. According to the National Comprehensive Cancer Network guidelines, segmental ureterectomy (SU) of upper tract urothelial carcinoma (UTUC) is a considerable option for selected mid- and distal ureteral urothelial carcinoma (UC). As a UTUC endemic area, Taiwan lacks treatment outcome analysis of SU. Materials and methods:. This study retrospectively reviewed the treatment outcomes of SU for clinically localized UTUCs. Patients with biopsy or washing cytology-confirmed UTUCs who underwent open, laparoscopic, or robot-assisted management with curative intent were retrospectively reviewed for the eligibility of analysis. Cox regression was applied for univariable and multivariable analyses. Results:. A total of 161 patients who underwent SU were reviewed and analyzed. The median follow-up period was 44.5 (interquartile range, 21.6–84.9) months. After SU, 56/161 (34.8%) patients were free of UTUCs after the follow-up, 25/161 (15.5%) patients had local recurrence, and 35/161 (21.7%) had lymph node or distant metastasis. Surgical margin involvement was a risk factor associated with worse cancer-specific survival. Higher bladder recurrence and local recurrence rates were observed with concurrent bladder UC. Lymphovascular invasion and previous radical nephroureterectomy (RNU) for UC were related to higher local recurrence rates. Patients with pathological T3/T4 stage and end-stage renal disease tended to have higher metastasis rates. For the management of local recurrence, 19 patients received salvage RNU and 25 patients had adjuvant chemotherapy. However, 26/161 (16.1%) patients died of UTUCs and 2/161 (1.2%) patients died of surgery-related complications. Conclusion:. SU provides acceptable oncological outcomes if the surgeons select candidates carefully. SU is not recommended if the patient has T3 or higher stage or comorbidity of end-stage renal disease. Concurrent bladder UC is a risk factor for worse bladder recurrence-free survival and local recurrence-free survival. Lymphovascular invasion and previous RNU for UC were related to higher local recurrence rates. After SU, periodic follow-up is mandatory because the local recurrence rate is higher than radical surgery.

BackgroundAzvudine, a repurposed oral small molecule antiviral drug, has potential effects in combating the SARS-CoV-2 virus. However, studies on its clinical efficacy in patients with COVID-19 are still limited and controversial, and further research and validation are necessary.MethodsA retrospective cohort study was conducted on COVID-19 patients who were hospitalized in the General Hospital of Central Theater Command from 1 December 2022 to 31 January 2023. We included 132 patients treated with Azvudine and 132 controls after screening and propensity score matching. The primary outcomes including all-cause mortality and a composite outcome of disease progression such as non-invasive respiratory support, invasive respiratory support, admission to intensive care unit (ICU), and death were compared.ResultsAzvudine recipients had a much lower incidence rate of composite disease progression outcome than controls (13.9075/1000 person-days versus 25.7731/1000 person-days, P

BackgroundAlthough large language models (LLMs) have demonstrated powerful capabilities in general domains, they may output information in the medical field that could be incorrect, incomplete, or fabricated. They are also unable to answer personalized questions related to departments or individual patient health. Retrieval-augmented generation technology (RAG) can introduce external knowledge bases and utilize the retrieved information to generate answers or text, thereby enhancing prediction accuracy.MethodWe introduced internal departmental data and 17 commonly used gastroenterology guidelines as a knowledge base. Based on RAG, we developed the Endo-chat medical chat application, which can answer patient questions related to gastrointestinal endoscopy. We then included 200 patients undergoing gastrointestinal endoscopy, randomly divided into two groups of 100 each, for a questionnaire survey. A comparative evaluation was conducted between the traditional manual methods and Endo-chat.ResultsCompared to ChatGPT, Endo-chat can accurately and professionally answer relevant questions after matching the knowledge base. In terms of response efficiency, completeness, and patient satisfaction, Endo-chat outperformed manual methods significantly. There was no statistical difference in response accuracy between the two. Patients showed a preference for AI services and expressed support for the introduction of AI. All participating nurses in the survey believed that introducing AI could reduce nursing workload.ConclusionIn clinical practice, Endo-chat can be used as a highly effective auxiliary tool for digestive endoscopic care.

The high inductance current ripple and the PV voltage fluctuations limitation at the DC (direct current) -DC link have been the unsolved problems in the photovoltaic systems tied in grid. A control strategy with a current hysteresis loop is proposed to address the issues of high inductance current ripple in photovoltaic systems which can achieve real-time duty cycle regulation. Differing from the conventional mode that uses one switch in the buck–boost DC–DC link, two switches have been designed here to separate the buck and boost modes for the coordinated control, which can achieve a wide PV voltage fluctuations range. Based on the conventional fixed-duty cycle determination method, a real-time duty cycle determination method is proposed by introducing changes in inductance current. In order to improve power conversion efficiency, the incremental conductance method is improved by introducing the steepest gradient descent to quickly achieve the maximum power point tracking. This study experimentally verifies the proposed current hysteresis coordinated control method, effectively suppressing the ripple of the inductor current and expand the PV voltage fluctuation in the DC–DC link on the basis of maintaining power conversion efficiency as much as possible.

Abstract Background The ligamentum flavum (LF) degeneration is a critical factor in spinal stenosis, leading to nerve compression and pain. Even with new treatment options becoming available, it is vital to have a better understanding of LF degeneration to ensure the effectiveness of these treatments. Objective This study aimed to provide insight into LF degeneration by examining the connections between various aspects of LF degeneration, including histology, microstructure, chemical composition, and biomechanics. Method We analyzed 30 LF samples from 27 patients with lumbar vertebrae, employing magnetic resonance imaging (MRI) to link lumbar disc degeneration grades with fibrosis levels in the tissue. X‐ray diffraction (XRD) analysis assessed microstructural alterations in the LF matrix component due to degeneration progression. Instrumented nanoindentation combined with Raman spectroscopy explored the spatial microbiomechanical and biochemical characteristics of the LF's ventral and dorsal regions. Results Our outcomes revealed a clear association between the severity of LF fibrosis grades and increasing LF thickness. XRD analysis showed a rise in crystalline components and hydroxyapatite molecules with progressing degeneration. Raman spectroscopy detected changes in the ratio of phosphate, proteoglycan, and proline/hydroxyproline over the amide I band, indicating alterations in the extracellular matrix composition. Biomechanical testing demonstrated that LF tissue becomes stiffer and less extensible with increasing fibrosis. Discussion Notably, the micro‐spatial assessment revealed the dorsal side of the LF experiencing more significant mechanical stress, alongside more pronounced biochemical and biomechanical changes compared to the ventral side. Degeneration of the LF involves complex processes that affect tissue histology, chemical composition, and biomechanics. It is crucial to fully understand these changes to develop new and effective treatments for spinal stenosis. These findings can improve diagnostic accuracy, identify potential biomarkers and treatment targets, guide personalized treatment strategies, advance tissue engineering approaches, help make informed clinical decisions, and educate patients about LF degeneration.

The occurrence of hyperuricemia (HUA; elevated serum uric acid) in athletes is relatively high despite that exercise can potentially reduce the risk of developing this condition. Although recent studies have shown the beneficial properties of DAG in improving overall metabolic profiles, a comprehensive understanding of the effect of DAG in modulating HUA in athletes is still lacking. In this study, we leveraged combinatorial lipidomics and metabolomics to investigate the effect of replacing TAG with DAG in the diet of athletes with HUA. A total of 1,074 lipids and metabolites from 94 classes were quantitated in serum from 33 athletes, who were categorized into responders and non-responders based on whether serum uric acid levels returned to healthy levels after the DAG diet intervention. Lipidomics and metabolomics analyses revealed lower levels of xanthine and uric acid in responders, accompanied by elevated plasmalogen phosphatidylcholines and diminished acylcarnitine levels. Our results highlighted the mechanisms behind how the DAG diet circumvented the risk and effects associated with high uric acid via lowered triglycerides at baseline influencing the absorption of DAG resulting in a decline in ROS and uric acid production, increased phospholipid levels associated with reduced p-Cresol metabolism potentially impacting on intestinal excretion of uric acid as well as improved ammonia recycling contributing to decreased serum uric acid levels in responders. These observed alterations might be suggestive that successful implementation of the DAG diet can potentially minimize the likelihood of a potentially vicious cycle occurring in high uric acid, elevated ROS, and impaired mitochondrial metabolism environment.

Coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), is an emergent disease that threatens global health. Public health structures and economic activities have been disrupted globally by the COVID-19 pandemic. Over 556.3 million confirmed cases and 6.3 million deaths have been reported. However, the exact mechanism of its emergence in humans remains unclear. SARS-CoV-2 is believed to have a zoonotic origin, suggesting a spillover route from animals to humans, which is potentially facilitated by wildlife farming and trade. The COVID-19 pandemic highlighted the importance of the One Health approach in managing threats of zoonosis in the human-animal-environment interaction. Implementing vigilant surveillance programs by adopting the One Health concept at the interfaces between wildlife, livestock, and humans is the most pertinent, practical, and actionable strategy for preventing and preparing for future pandemics of zoonosis, such as COVID-19 infection. This review summarizes the updated evidence of CoV infections in humans and animals and provides an appropriate strategy for preventive measures focused on surveillance systems through an On Health approach.

Summary: Cardiovascular diseases (CVDs) and metabolic disorders (MDs) have surfaced as formidable challenges to global health, significantly imperiling human well-being. Recently, microneedles (MNs) have garnered substantial interest within the realms of CVD and MD research. Offering a departure from conventional diagnostic and therapeutic methodologies, MNs present a non-invasive, safe, and user-friendly modality for both monitoring and treatment, thereby marking substantial strides and attaining pivotal achievements in this avant-garde domain, while also unfurling promising avenues for future inquiry. This thorough review encapsulates the latest developments in employing MNs for both the surveillance and management of CVDs and MDs. Initially, it succinctly outlines the foundational principles and approaches of MNs in disease surveillance and therapy. Subsequently, it delves into the pioneering utilizations of MNs in the surveillance and management of CVDs and MDs. Ultimately, this discourse synthesizes and concludes the primary findings of this investigation, additionally prognosticating on the trajectory of MN technology.

ABSTRACT: Toxoplasma gondii (T. gondii) is an intracellular protozoan that can cause toxoplasmosis in all warm-blooded hosts. This study focused on the prevalence and genetic characterize of T. gondii in ducks from Fujian province, China. Genomic DNA was extracted from duck tissue samples (heart, liver, lung, and muscle). To assess the genetic diversity of the T. gondii isolates, it was determined by using multilocus polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. A total of 586 ducks from 5 cities in Fujian province were tested, and 35 (6.0%) of which were found to be positive for the T. gondii B1 gene. Further genotyping of these positive samples at 10 genetic markers (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico) using PCR-RFLP revealed that one tissue samples (heart samples from Fuzhou ducks) were identified as Type I (ToxoDB#10). This study is the first report on the prevalence and genetic characterization of T. gondii in ducks in Fujian province, and Type I (ToxoDB#10) is found in ducks in China for the first time. The findings document the genetic characterization of T. gondii in free-range ducks from Fujian Province, thereby enriching the understanding of T. gondii genetic diversity in China. Moreover, these results provide essential data support for further prospective studies and underscores the “One Health” concept, emphasizing the integral link among human, animal, and environmental health.

During the capillary underfill (CUF) process in flip-chip packaging, issues like incomplete filling, voids, wire sweeping, and overflow can impact product reliability and the relatively long filling time required. Therefore, finding ways to improve filling efficiency is a critical challenge. Conducting experiments to address these issues can be costly. As a result, the industry often relies on simulation software to simulate the actual manufacturing process, predict potential problems, compare results with experimental data, and analyze ways to improve the process. This approach helps enhance the package yield and further improves production efficiency.This study investigates the capillary underfill (CUF) process through simulation. Firstly, the viscosity and reaction kinetics of the underfill material are measured to establish the necessary data for the simulation. Then, Moldex3D, a mold flow simulation software, is used to create the model, generate the mesh, and perform the process simulation analysis. The effects of material properties and process parameters on the capillary underfill process are considered. The simulation results are compared with experimental data to validate the feasibility of the simulation. Subsequently, different flip-chip package structures and CUF process parameters are analyzed through simulation to explore the impact of these parameters on the flow pattern and filling efficiency of the adhesive material during the filling process.According to the simulation results, the filling speed is faster when the bump pitch and gap height are larger. However, the required filling time still has a considerable relationship with the volume of the filling region. Dispensing from the side with lower bump density can shorten the filling time when the bump distribution is uneven.