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Abstract Background The long-term impacts of COVID-19 on human health are a major concern, yet comprehensive evaluations of its effects on various health conditions are lacking. Methods This study aims to evaluate the role of various diseases in relation to COVID-19 by analyzing genetic data from a large-scale population over 2,000,000 individuals. A bidirectional two-sample Mendelian randomization approach was used, with exposures including COVID-19 susceptibility, hospitalization, and severity, and outcomes encompassing 86 different diseases or traits. A reverse Mendelian randomization analysis was performed to assess the impact of these diseases on COVID-19. Results Our analysis identified causal relationships between COVID-19 susceptibility and several conditions, including breast cancer (OR = 1.0073, 95% CI = 1.0032–1.0114, p = 5 × 10 − 4), ER + breast cancer (OR = 0.5252, 95% CI = 0.3589–0.7685, p = 9 × 10 − 4), and heart failure (OR = 1.0026, 95% CI = 1.001–1.0042, p = 0.002). COVID-19 hospitalization was causally linked to heart failure (OR = 1.0017, 95% CI = 1.0006–1.0028, p = 0.002) and Alzheimer’s disease (OR = 1.5092, 95% CI = 1.1942–1.9072, p = 0.0006). COVID-19 severity had causal effects on primary biliary cirrhosis (OR = 2.6333, 95% CI = 1.8274–3.7948, p = 2.059 × 10 − 7), celiac disease (OR = 0.0708, 95% CI = 0.0538–0.0932, p = 9.438 × 10–80), and Alzheimer’s disease (OR = 1.5092, 95% CI = 1.1942–1.9072, p = 0.0006). Reverse MR analysis indicated that rheumatoid arthritis, diabetic nephropathy, multiple sclerosis, and total testosterone (female) influence COVID-19 outcomes. We assessed heterogeneity and horizontal pleiotropy to ensure result reliability and employed the Steiger directionality test to confirm the direction of causality. Conclusions This study provides a comprehensive analysis of the causal relationships between COVID-19 and diverse health conditions. Our findings highlight the long-term impacts of COVID-19 on human health, emphasizing the need for continuous monitoring and targeted interventions for affected individuals. Future research should explore these relationships to develop comprehensive healthcare strategies.

In order to accurately measure the workplace \begin{document}$ {{\dot{H}}'\left(0.07\right) } $\end{document}in real time，the ZF-FD7 online \begin{document}$ {{\dot{H}}'\left(0.07\right) } $\end{document} monitoring system was developed. Its detector is based on plastic scintillator and SiPM，and the developed intermediate machine and upper computer have data transmission，dose rate display，over-threshold alarm and other functions. For the developed on-line \begin{document}$ {{\dot{H}}'\left(0.07\right) } $\end{document}monitoring system，the radiation characteristics measured by reference to GB/T4835.1-2012 are as follows: in the range of 76 μSv/h-1.4 Sv/h，its relative inherent error is within ±10%; The average energy of the β ray is 60-800 keV，and the response is within the range of 0.8-1.2; At −45°- 45º incidence，the response of the incidence angle is between 0.88-1.00; The repeatability of the measurement results in a 1 mSv/h radiation field is 2.0%. After temperature compensation，the response change is 0.91-1.08 within −10 ℃- 40 ℃，and 0.93-1.00 in the range of relative humidity of 45%-85%. The test results show that the characteristics of the ZF-FD7 on-line \begin{document}$ {{\dot{H}}'\left(0.07\right) } $\end{document} monitoring system meet the requirements of GB/T4835.1-2012，and can be used for real-time monitoring of directional dose equivalent rate in high weak penetrating radiation sites

Abstract Background To review the changes and survey on status quo of the surgical treatment for esophageal cancer in China. The differences in diagnosis and treatment for esophageal cancer among hospitals in different regions across China were also investigated. Methods We sent questionnaires to 46 hospitals across China, investigating the volume of esophageal cancer surgeries, surgical procedures, and perioperative management under the guidance of esophageal surgery chiefs. Results A total of 46 questionnaires were sent out and collected. The survey results showed that in the past 5 years, the volume of surgeries for esophageal cancer remained stable by 23.9% of those hospitals, increased by 30.4%, and decreased by 45.7%. Of those patients treated by surgery, 19.1% were in the early stages, and 80.9% were in locally advanced stages. In terms of surgical procedures, 73.4% of the patients were treated by minimally invasive surgery and 85.7% of esophageal substitutes were a gastric conduit, 93.1% of the substitutes were pulled to the neck through the esophageal bed. For the lymph node dissection, 78.5% of the patients had a complete two‐field lymph node dissection including the para‐recurrent laryngeal nerve lymph nodes. Of the patients with neoadjuvant therapy, 53.5% received chemotherapy or chemotherapy plus immunotherapy (47.0%), and 43.5% had chemoradiation. Conclusions Currently, in China, minimally invasive surgery‐oriented multimodality treatment, including complete two‐field lymph node dissection, has become the standard approach for esophageal cancer management. Over the past decade, this standardized approach has significantly improved prognosis compared to previous decades.

Abstract Background Lifestyle has become a crucial modulator in the management of diabetes and is intimately linked with the development and exacerbation of comorbid depression. The study aimed to analyze lifestyle patterns and their impact on depression in individuals with diabetes and to explore the role of the Dietary Inflammatory Index (DII) in the relationship between lifestyle patterns and depression. Methods Data was attained from the National Health and Nutrition Examination Survey (NHANES) between 2009 and 2020. A latent class analysis (LCA) was performed on 3,009 diabetic adults based on lifestyle behaviors. A generalised linear model (GLM) was employed to analyse the effects of different lifestyle patterns on depression. The mediation effect model was utilised to examine the relationship between lifestyle patterns, DII and Patient Health Questionnaire-9 (PHQ-9) scores. Results The cohort was divided through LCA into unhealthy lifestyle (44.53%), unhealthy but non-alcohol use (48.06%) and healthy but smoking (7.41%) groups of lifestyle behaviors, the unhealthy but non-alcohol use group was identified as a risk factor for depression (OR = 1.379, 95%CI = 1.095 ~ 1.735, P = 0.006). The DII partially mediated the relationship between the unhealthy but non-alcohol use group and PHQ-9, and fully mediated the relationship between the healthy but smoking group and PHQ-9, with effect coefficients of − 0.018 (95%CI: −0.044 ~ − 0.001) and − 0.035 (95%CI: −0.083 ~ − 0.001). Conclusions Lifestyle patterns significantly influence the occurrence of depression among diabetes patients. The dietary inflammation plays a varying mediating role between different lifestyle patterns and depression. Restricting pro-inflammatory diets or encouraging anti-inflammatory diets, combined with the promotion of healthy lifestyle practices, may be an effective method for preventing and alleviating symptoms of depression among patients with diabetes.

Introduction: Reverse genetic studies conducted in the plant with a complex or polyploidy genome enriched with large gene families (like wheat) often meet challenges in identifying the key candidate genes related to important traits and prioritizing the genes for functional experiments. Objective: To overcome the above-mentioned challenges of reverse genetics, this work aims to establish an efficient multi-species strategy for genome-wide gene identification and prioritization of the key candidate genes. Methods: We established the integrative gene duplication and genome-wide analysis (iGG analysis) as a strategy for pinpointing key candidate genes deserving functional research. The iGG captures the evolution, and the expansion/contraction of large gene families across phylogeny-related species and integrates spatial–temporal expression information for gene function inference. Transgenic approaches were also employed to functional validation. Results: As a proof-of-concept for the iGG analysis, we took the wheat calcineurin B-like protein-interacting protein kinases (CIPKs) family as an example. We identified CIPKs from seven monocot species, established the orthologous relationship of CIPKs between rice and wheat, and characterized Triticeae-specific CIPK duplicates (e.g., CIPK4 and CIPK17). Integrated with our analysis of CBLs and CBL-CIPK interaction, we revealed that divergent expressions of TaCBLs and TaCIPKs could play an important role in keeping the stoichiometric balance of CBL-CIPK. Furthermore, we validated the function of TaCIPK17-A2 in the regulation of drought tolerance by using transgenic approaches. Overexpression of TaCIPK17 enhanced antioxidant capacity and improved drought tolerance in wheat. Conclusion: The iGG analysis leverages evolutionary and comparative genomics of crops with large genomes to rapidly highlight the duplicated genes potentially associated with speciation, domestication and/or particular traits that deserve reverse-genetic functional studies. Through the identification of Triticeae-specific TaCIPK17 duplicates and functional validation, we demonstrated the effectiveness of the iGG analysis and provided a new target gene for improving drought tolerance in wheat.

Abstract Early-life exposure to stress results in significantly increased risk of neurodevelopmental impairments with potential long-term effects into childhood and even adulthood. As a crucial step towards monitoring neonatal stress in neonatal intensive care units (NICUs), our study aims to quantify the duration, frequency, and physiological responses of care manipulation activities, based on bedside videos and physiological signals. Leveraging 289 h of video recordings and physiological data within 330 sessions collected from 27 neonates in 2 NICUs, we develop and evaluate a deep learning method to detect manipulation activities from the video, to estimate their duration and frequency, and to further integrate physiological signals for assessing their responses. With a 13.8% relative error tolerance for activity duration and frequency, our results were statistically equivalent to human annotations. Further, our method proved effective for estimating short-term physiological responses, for detecting activities with marked physiological deviations, and for quantifying the neonatal infant stressor scale scores.

Abstract A wideband end‐fire stepped slot antenna with gain enhancement and filtering capability is proposed. On one hand, a parasitic dipole serving as a director is introduced in the stepped slot to improve the radiation gain of the slot antenna without increasing its physical size. It is found that a gain enhancement of about 2 dB can be achieved after adopting such approach. On the other hand, an absorptive branch possessing a nearly complementary frequency response with regard to the one of the slot antenna is in‐parallel loaded at the microstrip feedline. It allows the partial dissipation of the out‐of‐band/non‐radiated RF‐signal power of the antenna to attain both an RF‐quasi‐absorptive behaviour and filtering capability. It is found that after loading the dissipative branch, the out‐of‐band radiation efficiency of the slot antenna is reduced to less than 20%. The measured results of a fabricated proof‐of‐concept antenna prototype show a reasonable agreement with the simulated ones and verify the RF performance merits of the proposed stepped slot antenna, such as wide RF operating band covering the 3.39−4.73‐GHz range, end‐fire radiation with a front‐to‐back ratio (FBR) above 10 dB, flat radiation gain, and co‐integrated filtering functionality with RF‐quasi‐absorptive capability.

Abstract Background The role of tumor-draining lymph nodes in the progression of malignant tumors, including stage III colorectal cancer (CRC), is critical. However, the prognostic and predictive value of the number of examined lymph nodes (ELNs) are not fully understood. Methods This population-based study retrospectively analyzed data from 106,843 patients with stage III CRC who underwent surgical treatment and registered in three databases from 2004 to 2021. The Surveillance, Epidemiology, and End Results (SEER) cohort was divided using into training and test cohorts at a ratio of 3:2. We employed restricted cubic spline (RCS) curves to explore nonlinear relationships between overall survival (OS) and ELNs counts and performed Cox regression to evaluate hazard ratios across different ELNs count subtypes. Additional validation cohorts were utilized from the First Affiliated Hospital, Sun Yat-sen University and The Cancer Genome Atlas (TCGA) under the same criteria. Outcomes measured included OS, cancer-specific survival (CSS), and progression-free survival (PFS). Molecular analyses involved differential gene expression using the “limma” package and immune profiling through CIBERSORT. Tissue microarray slides and multiplex immunofluorescence (MIF) were used to assess protein expression and immune cell infiltration. Results Patients with higher ELNs counts (≥ 17) demonstrated significantly better long-term survival outcomes across all cohorts. Enhanced OS, CSS, and PFS were notably evident in the LN-ELN group compared to those with fewer ELNs. Cox regression models underscored the prognostic value of higher ELNs counts across different patient subgroups by age, sex, tumor differentiation, and TNM stages. Subtype analysis based on ELNs count revealed a marked survival benefit in patients treated with adjuvant chemotherapy in the medium and large ELNs counts (≥ 12), whereas those with fewer ELNs showed negligible benefits. RNA sequencing and MIF indicated elevated immune activation in the LN-ELN group, characterized by increased CD3+, CD4+, and CD8 + T cells within the tumor microenvironment. Conclusions The number of ELNs independently predicts survival and the immunological landscape at the tumor site in stage III CRC, underscoring its dual prognostic and predictive value.

Abstract Background To investigate the changes in the unhealthy eye-related behaviors of junior middle school students during the COVID-19 pandemic and the double reduction policy and its relationship with myopia. Methods Data were obtained from the 2019–2022 Tianjin Children and Youth Myopia, Common Diseases and Health Influencing Factors Survey. Latent profile analysis (LPA) and a generalized linear model (GLM) were applied to analyze the effect of eye-related behavior classes on myopia. Results A total of 2508 junior middle school students were included. The types of eye-related behavior were categorized into the medium-healthy behavior group, heavy academic burden and near-eye behavior group, insufficient lighting group and high-healthy behavior group. Students with heavy academic burdens and near-eye behavior were more likely to develop myopia than were those in the high-healthy group (OR = 1.466, 95% CI = 1.203–1.787; P

The application of deep learning in neuroscience holds unprecedented potential for unraveling the complex dynamics of the brain. Our bibliometric analysis, spanning from 2012 to 2023, delves into the integration of deep learning in neuroscience, shedding light on the evolutionary trends and identifying pivotal research hotspots. Through the examination of 421 articles, this study unveils a significant growth in interdisciplinary research, marked by the burgeoning application of deep learning techniques in understanding neural mechanisms and addressing neurological disorders. Central to our findings is the critical role of classification algorithms, models, and neural networks in advancing neuroscience, highlighting their efficacy in interpreting complex neural data, simulating brain functions, and translating theoretical insights into practical diagnostics and therapeutic interventions. Additionally, our analysis delineates a thematic evolution, showcasing a shift from foundational methodologies toward more specialized and nuanced approaches, particularly in areas like EEG analysis and convolutional neural networks. This evolution reflects the field’s maturation and its adaptation to technological advancements. The study further emphasizes the importance of interdisciplinary collaborations and the adoption of cutting-edge technologies to foster innovation in decoding the cerebral code. The current study provides a strategic roadmap for future explorations, urging the scientific community toward areas ripe for breakthrough discoveries and practical applications. This analysis not only charts the past and present landscape of deep learning in neuroscience but also illuminates pathways for future research, underscoring the transformative impact of deep learning on our understanding of the brain.

BackgroundThe standardized extract of milk thistle seeds, known as silibinin, has been utilized in herbal medicine for over two centuries, with the aim of safeguarding the liver against the deleterious effects of various toxic substances. However, the role of silibinin in Particulate Matter (PM2.5)-induced intrahepatic triglyceride accumulation remains unclear. This study seeks to investigate the impact of silibinin on PM2.5-induced intrahepatic triglyceride accumulation and elucidate potential underlying mechanisms.MethodsA model of intrahepatic triglyceride accumulation was established in male C57BL/6J mice through intratracheal instillation of PM2.5, followed by assessment of liver weight, body weight, liver index, and measurements of intrahepatic triglycerides and cholesterol after treatment with silibinin capsules. Hep G2 cells were exposed to PM2.5 suspension to create an intracellular triglyceride accumulation model, and after treatment with silibinin, cell viability, intracellular triglycerides and cholesterol, fluorescence staining for Nile Red (lipid droplets), and DCFH-DA (Reactive Oxygen Species, ROS), as well as proteomics, real-time PCR, and mitochondrial function assays, were performed to investigate the mechanisms involved in reducing triglycerides.ResultsPM2.5 exposure leads to triglyceride accumulation, increased ROS production, elevated expression of inflammatory factors, decreased expression of antioxidant factors, and increased expression of downstream genes of aryl hydrocarbon receptor. Silibinin can partially or fully reverse these factors, thereby protecting cells and animal livers from PM2.5-induced damage. In vitro studies show that silibinin exerts its protective effects by preserving oxidative phosphorylation of mitochondrial complexes I and II, particularly significantly enhancing the function of mitochondrial complex II. Succinate dehydrogenase (mitochondrial complex II) is a direct target of silibinin, but silibinin A and B exhibit different affinities for different subunits of complex II.ConclusionSilibinin improved the accumulation of intrahepatic triglycerides induced by PM2.5, and this was, at least in part, explained by an enhancement of oxidative phosphorylation in mitochondrial Complexes I and II.

Protective vaccines are crucial for preventing and controlling coronavirus disease 2019 (COVID-19). Updated vaccines are needed to confront the continuously evolving and circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. These vaccines should be safe, effective, amenable to easily scalable production, and affordable. Previously, we developed receptor binding domain (RBD) dimer-based protein subunit vaccines (ZF2001 and updated vaccines) in mammalian cells. In this study, we explored a strategy for producing RBD-dimer immunogens in Pichia pastoris. We found that wild-type P. pastoris produced hyperglycosylated RBD-dimer protein containing four N-glycosylation sites in P. pastoris. Therefore, we engineered the wild type P. pastoris (GS strain) into GSΔOCH1pAO by deleting the OCH1 gene (encoding α-1,6-mannosyltransferase enzyme) to decrease glycosylation, as well as by overexpressing the HIS4 gene (encoding histidine dehydrogenase) to increase histidine synthesis for better growth. In addition, RBD-dimer protein was truncated to remove the R328/F329 cleavage sites in P. pastoris. Several homogeneous RBD-dimer proteins were produced in the GSΔOCH1pAO strain, demonstrating the feasibility of using the P. pastoris expression system. We further resolved the cryo-EM structure of prototype-Beta RBD-dimer complexed with the neutralizing antibody CB6 to reveal the completely exposed immune epitopes of the RBDs. In a murine model, we demonstrated that the yeast-produced RBD-dimer induces robust and protective antibody responses, which is suitable for boosting immunization. This study developed the yeast system for producing SARS-CoV-2 RBD-dimer immunogens, providing a promising platform and pipeline for the future continuous updating and production of SARS-CoV-2 vaccines.

[Objective] To scientifically understand the spatio-temporal evolution process and formation mechanism of urban space, agricultural space and ecological space in Qinling-Daba Mountain area is the key to promote the overall coordination of the national spatial development pattern and the rise of the central and western regions, and it is also an urgent need for high-quality transformation and development of the region. [Methods] Based on the methods of spatial transfer matrix, topographic location analysis and random forest regression, the spatial and temporal evolution characteristics and driving mechanism of Qinba Mountain region during 2000—2020 were studied from two dimensions of “pattern scale-topographic location”. [Results] (1) In the past 20 years, the cities and towns in the Qinba Mountain area expanded dramatically, and the agricultural and ecological space continued to shrink. While the population of 58.33% of the counties decreased, the urban land was still expanding, and the “total population and urban size” showed a serious polarization. (2) The phenomenon was characterized by urban and agricultural space “climbing up the hills”, while ecological space “descended into the valleys”. The newly added urban and agricultural space was moved up 1 to 2 topographic positions on average. The dam elevation project of Danjiangkou Reservoir downstream had a significant impact on the overall spatial distribution gradient of the mountainous areas. (3) The dynamic adjustment and replacement of “agricultural space to ecological space” was the leading type of transformation in Qinba Mountain area, and the influence of fiscal expenditure was the most significant. Agricultural space was the main source of new towns, and the scale of urban degradation into agricultural and ecological space was significant in Qinba mountain area. (4) Land development policies, mountain terrain attributes, traffic location conditions and social and economic factors jointly restrict and affect the results of territorial spatial evolution in Qinba Mountain area, and there were obvious differences in the effect intensity and the number of significant factors of various types of factors in different conversion directions. [Conclusion] Promoting the concentration of new towns to the key development zones, scientifically guiding agricultural and ecological space to conform to the topographic gradient layout, carefully carrying out water conservancy project construction, and planning the overall regional layout of the “Three districs and Three lines” will have a positive impact on the optimization of territorial spatial pattern in Qinba Mountain area.

Abstract A kind of all‐dielectric circularly polarised (CP) loop antenna made of high‐permittivity material is proposed. The leaky‐wave radiation from a high‐permittivity dielectric waveguide is utilised here to support the operation of the proposed antenna. A non‐closed dielectric loop covering a three‐quarter circle is adopted to generate CP radiation and it is connected with the dielectric ground via one of bending ends to form an all‐in‐one structure of the antenna. The other end is also bent and vertical to the ground, but hanging in the air for probe feed. As two kinds of typical high‐permittivity dielectric materials, zirconia ceramic and pure water are used to implement the proposed design respectively. On one hand, an all‐ceramic CP loop antenna made of zirconia is proposed. And benefiting from the low loss and high melting point of zirconia, the proposed ceramic antenna has superiority in radiation efficiency and could adapt to a harsh environment. On the other hand, by using pure water and transparent container, a fully‐transparent CP water loop antenna can be obtained. Finally, a 3‐D printing technology is adopted in the manufacturing of ceramic structure and resin container. Measured results of both antennas demonstrate the validity of the proposed design.

Abstract Taiwanofungus camphoratus has attracted much attention because it can abundantly produce various active substances that exhibit blood-sugar lowering, immunity improving, and antioxidant properties. Currently, T. camphoratus is cultured using four main methods: cutting wood culture, solid-state fermentation, submerged fermentation, and dish culture. T. camphoratus produces different metabolites under different culture methods. In this study, nontargeted metabolomics was used to compare the metabolites of T. camphoratus produced under these four culture methods. Principal component analysis and supervised partial least squares-discriminant analysis were used to analyze the differences in the metabolites. Moreover, in vitro hypoglycemic activity of T. camphoratus extracts produced under four culture methods was compared by assessing their ability to inhibit the activity of α-glucosidase, α-amylase, and sucrase. A total of 186 metabolites were identified. In total, 127 metabolites were common under the four culture methods. Under solid-state fermentation, submerged fermentation, and cutting wood culture, 12, 1, and 4 metabolites were unique, respectively. The differential metabolites produced by T. camphoratus under four culture methods were mainly triterpenoids, phenolic compounds, and fatty acid compounds. α-glucosidase, α-amylase, and sucrase activity inhibition was the best using T. camphoratus extract obtained under cutting wood culture; the inhibition rates were 55.97%, 51.96%, and 78.02%, respectively, which were comparable to those exhibited by 0.001, 3, and 12 mg/mL acarbose (positive control). The metabolites produced by T. camphoratus and α-glucosidase, α-amylase, and sucrase inhibitory activities were different under the four culture methods. Cutting wood culture exhibited the best enzyme inhibitory activity. This study provided a theoretical basis for further use and development of various culture methods for the rational production of active metabolites of T. camphoratus.

Abstract Background The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. Methods A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. Results After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P

Abstract Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (60 mg/m2) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC.

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is a pivotal enzyme that mediates the fixation of CO2. As the most abundant protein on earth, Rubisco has a significant impact on global carbon, water, and nitrogen cycles. However, the significantly low carboxylation activity and competing oxygenase activity of Rubisco greatly impede high carbon fixation efficiency. This review first summarizes the current efforts in directly or indirectly modifying plant Rubisco, which has been challenging due to its high conservation and limitations in chloroplast transformation techniques. However, recent advancements in understanding Rubisco biogenesis with the assistance of chaperones have enabled successful heterologous expression of all Rubisco forms, including plant Rubisco, in microorganisms. This breakthrough facilitates the acquisition and evaluation of modified proteins, streamlining the measurement of their activity. Moreover, the establishment of a screening system in E. coli opens up possibilities for obtaining high-performance mutant enzymes through directed evolution. Finally, this review emphasizes the utilization of Rubisco in microorganisms, not only expanding their carbon-fixing capabilities but also holding significant potential for enhancing biotransformation processes.

Abstract The complexity of the tumor microenvironment (TME) is a crucial factor in lung adenocarcinoma (LUAD) progression. To gain deeper insights into molecular mechanisms of LUAD, we perform an integrative single-cell RNA sequencing (scRNA-seq) data analysis of 377,574 cells from 117 LUAD patient samples. By linking scRNA-seq data with bulk gene expression data, we identify a cluster of prognostic-related UPP1high tumor cells. These cells, primarily situated at the invasive front of tumors, display a stronger association with the immunosuppressive components in the TME. Our cytokine array analysis reveals that the upregulation of UPP1 in tumor cells leads to the increased release of various immunosuppressive cytokines, with TGF-β1 being particularly prominent. Furthermore, this UPP1 upregulation also elevates the expression of PD-L1 through the PI3K/AKT/mTOR pathway, which contributes to the suppression of CD8 + T cells. Cytometry by time-of-flight (CyTOF) analysis provides additional evidence of the role of UPP1 in shaping the immunosuppressive nature of the TME. Using patient-derived organoids (PDOs), we discover that UPP1high tumors exhibit relatively increased sensitivity to Bosutinib and Dasatinib. Collectively, our study highlights the immunosuppressive role of UPP1 in LUAD, and these findings may provide insights into the molecular features of LUAD and facilitate the development of personalized treatment strategies.

ABSTRACT: We previously identified a dark blue appearance through the skin of abdomen, especially the colored chicken breeds, called hyperpigmentation of the visceral peritoneum (HVP) which characterized by intense pigmentation of connective tissue in the visceral peritoneum. The HVP has recently garnered increasing attention due to its negative impact on carcass appearance, and been an important concern in the poultry industry, especially for the Chinese yellow-feathered broilers. In this study, we measured the in vivo HVP at different time points, and analyzed the correlation between the HVP in vivo and postmortem. Then, established an accurate and reliable HVP phenotypic measuring method in vivo for early selection in chickens and analyzed the association of phenotypic variations with the in vivo HVP traits with growth traits. The results showed that the in vivo HVP at 21 d of age in chickens have a high heritability (h2 = 0.452) through estimating genetic parameters, and in vivo HVP levels at 21 and 42 d were both significantly associated with those postmortem in chickens, suggesting that directional selection on reducing HVP can be implemented as early as at 21 d in the breeding and production of chickens. Although, we found HVP had no effect on the body weight at 1 d, it could significantly reduce the body weight at 21, 42, 70 d and 91 d in chickens. This suggests HVP not only has a negative effect on carcass traits, but also significantly reduces the production in the poultry industry.

ObjectiveSubcutaneous Immunotherapy (SCIT) is the long-lasting causal treatment of allergic rhinitis (AR). How to enhance the adherence of patients to maximize the benefit of allergen immunotherapy (AIT) plays a crucial role in the management of AIT. This study aims to leverage novel machine learning models to precisely predict the risk of non-adherence of AR patients and related local symptom scores in 3 years SCIT.MethodsThe research develops and analyzes two models, sequential latent-variable model (SLVM) of Stochastic Latent Actor-Critic (SLAC) and Long Short-Term Memory (LSTM). SLVM is a probabilistic model that captures the dynamics of patient adherence, while LSTM is a type of recurrent neural network designed to handle time-series data by maintaining long-term dependencies. These models were evaluated based on scoring and adherence prediction capabilities.ResultsExcluding the biased samples at the first time step, the predictive adherence accuracy of the SLAC models is from 60% to 72%, and for LSTM models, it is 66%–84%, varying according to the time steps. The range of Root Mean Square Error (RMSE) for SLAC models is between 0.93 and 2.22, while for LSTM models it is between 1.09 and 1.77. Notably, these RMSEs are significantly lower than the random prediction error of 4.55.ConclusionWe creatively apply sequential models in the long-term management of SCIT with promising accuracy in the prediction of SCIT nonadherence in AR patients. While LSTM outperforms SLAC in adherence prediction, SLAC excels in score prediction for patients undergoing SCIT for AR. The state-action-based SLAC adds flexibility, presenting a novel and effective approach for managing long-term AIT.

Breast infection is the primary etiology of mastitis in dairy cows, leading to a reduction in the quality of dairy products and resulting in substantial economic losses for animal husbandry. Although antibiotic treatment can eliminate the pathogenic microorganisms that induce mastitis, it cannot repair the inflammatory damage of mammary epithelial cells and blood milk barrier. Mas1 is a G protein-coupled receptor, and its role in lipopolysaccharide (LPS) -induced inflammatory injury to mammary epithelial cells has not been studied. LPS treatment of EpH4 EV cells led to a significant downregulation of Mas1 transcript levels, which attracted our great interest, suggesting that Mas1 may be an important target for the treatment of mastitis. Therefore, this study intends to verify the role of Mas1 in the inflammatory injury of EpH4 EV cells by gene overexpression technology and gene silencing technology. The findings demonstrated that the overexpression of the Mas1 gene effectively reversed the activation of the nuclear factor-κB/mitogen-activated protein kinase (NF-κB/MAPK) signaling pathways induced by LPS, while also suppressing the upregulation of pro-inflammatory mediators. Furthermore, overexpression of the Mas1 gene reversed the downregulation of zonula occludens 1 (ZO-1), Occludin, and Claudin-3 caused by LPS, suggesting that Mas1 could promote to repair the blood-milk barrier. However, the silencing of the Mas1 gene using siRNA resulted in a contrasting effect. These results indicated that Mas1 alleviated the inflammatory injury of mammary epithelial cells induced by LPS.

Purpose: As the most common subset of breast cancer (BC), estrogen receptor positive (ER+) BC accounting for 80% of cases, has become a global public health concern. The female hormone estrogen (E2) unequivocally drives ER + breast malignancies. The reasons that estrogen affects BC development has long been considered, yet further study remains to be conducted of the molecular events in the E2-estrogen receptor α (ERα) signaling pathway in ER + BC progression, especially lipid metabolism, so providing more options for tailored and individualized therapy. Our aim is to find out new targets and clinical biomarkers for ER + breast cancer treatment from the perspective of lipid metabolism. Methods: Lipid metabolomics profiling was used to examine the membrane phospholipid stimulated by E2. Clinical BC samples were used to assess the association of CYP4F2, CYP4F11 expression with clinicopathological characteristics and patient outcomes. Some inhibitors of main enzymes in AA metabolism were used combined with E2 to assess roles of CYP4F2/CYP4F11 in the progression of ER + BC. CYP4F2, CYP4F11 overexpression and knockdown BC cell lines were employed to examine the effects of CYP4F2, CYP4F11 on cellular proliferation, apoptosis and tumor growth. Western blotting, qPCR, Immunohistochemical staining and flow cytometry were also conducted to determine the underlying mechanisms related to CYP4F2, CYP4F11 function. Results: The activation of the CYP450 signaling pathway in arachidonic acid metabolism contributed to ER + BC tumorigenesis. In ER + BC, CYP4F2 and CYP4F11 overexpression induced by E2 could promote cancer cell proliferation and resistance to apoptosis by producing the metabolite 20-HETE and activating the antiapoptotic protein Bcl-2. CYP4F2 and CYP4F11 elevation correlates with poorer overall survival and disease-free survival in ER + BC patients. Conclusion: CYP4F2, CYP4F11 and their metabolite 20-HETE could serve as effective prognostic markers and attractive therapeutic targets for novel anticancer drug development about ER + BC.

Aluminium-air batteries have been considered as one of the most promising next-generation energy storage devices. In this work, based on COMSOL Multiphysics, we firstly explored the effect of 3D pore size structure change on the permeation performance of the solution. The results showed that enhancing the permeation stroke of permeable solutions was beneficial to expanding the electrode reaction contact area, but it would reduce the permeation and corrosion resistance effects. For this reason, we further carried out a secondary study of TPMS structure on fluid permeation and its electrochemical performance based on the TPMS structure modelling mechanism. The results showed that the TPMS structure possessed both good solution permeation reaction rate and good corrosion resistance. Additionally, in order to further verify the validity of the simulation data, we carried out the validation of the self-corrosion rate, discharge properties, and electrochemical properties. From the final data, the discharge voltage of the TPMS structure was only 1.43 V, but its corrosion current and polarisation impedance were 2.207 × 10−2 A/cm2 and 2.2 Ω∙cm2, respectively. At the same time, the structure also had good solution permeability. Therefore the porous anode structure design for aluminium-air batteries in three-dimensional state is preferred.

Lithium slag (LS) is a waste residue generated during lithium extraction, posing significant environmental challenge due to its extensive accumulation. This study proposes a method of utilizing thermally activated LS as the sole precursor for geopolymer synthesis. The thermal activation mechanism of LS was investigated using XRD, FTIR, ICP, and SEM techniques, while exploring the optimal composition for LS geopolymers(LSG). The research revealed that heating at 700 °C increased the amorphous content of LS from 15.9 % to 48.1 %, altering the chemical structure of its aluminosilicates and enhancing its leaching capacity in alkaline environments, thereby boosting its reactivity. The activator modulus and alkali equivalent were found to significantly influence the strength and microstructure of LSG. As the modulus increased from 1.0 to 1.4, geopolymer strength initially rose before declining, whereas strength progressively increased with alkali equivalent from 0.10 to 0.16. The geopolymer synthesized with a modulus of 1.2 and alkali equivalent of 0.16 exhibited the highest compressive strength of 53.1 MPa after 28 days. Test results indicated that the internal structure of LSG primarily comprised unreacted particles, N(C)-A-S-H gel, and microcracks. The increased alkali equivalent facilitated the dissolution of Si4+ and Al3+ within LS, intensifying geopolymerization to produce more N(C)-A-S-H gel, thereby densifying the structure and significantly enhancing compressive strength. This study elucidates the mechanism by which high-temperature calcination enhances LS reactivity, as well as the impact of activator on compressive strength and microstructural properties of LSG, offering new insights into the engineering applications of LS in high-performance cementitious materials.

Heterogeneous photocatalysis emerges as an exceptionally appealing technological avenue for the direct capture, conversion, and storage of renewable solar energy, facilitating the generation of sustainable and ecologically benign solar fuels and a spectrum of other pertinent applications. Heterogeneous nanocomposites, incorporating Covalent Triazine Frameworks (CTFs), exhibit a wide-ranging spectrum of light absorption, well-suited electronic band structures, rapid charge carrier mobility, ample resource availability, commendable chemical robustness, and straightforward synthetic routes. These attributes collectively position them as highly promising photocatalysts with applicability in diverse fields, including but not limited to the production of photocatalytic solar fuels and the decomposition of environmental contaminants. As the field of photocatalysis through the hybridization of CTFs undergoes rapid expansion, there is a pressing and substantive need for a systematic retrospective analysis and forward-looking evaluation to elucidate pathways for enhancing performance. This comprehensive review commences by directing attention to diverse synthetic methodologies for the creation of composite materials. And then it delves into a thorough exploration of strategies geared towards augmenting performance, encompassing the introduction of electron donor–acceptor (D-A) units, heteroatom doping, defect Engineering, architecture of Heterojunction and optimization of morphology. Following this, it systematically elucidates applications primarily centered around the efficient generation of photocatalytic hydrogen, reduction of carbon dioxide through photocatalysis, and the degradation of organic pollutants. Ultimately, the discourse turns towards unresolved challenges and the prospects for further advancement, offering valuable guidance for the potent harnessing of CTFs in high-efficiency photocatalytic processes.

Abstract Natural photosynthesis holds great potential to generate clean electricity from solar energy. In order to utilize this process for power generation, it is necessary to rewire photosynthetic electron transport chains (PETCs) of living photosynthetic organisms to redirect more electron flux toward an extracellular electrode. In this study, a semi‐artificial rewiring strategy, which use a water‐soluble fullerene derivative to capture electrons from PETCs and donate them for electrical current generation, is proposed. A positively charged fullerene derivative, functionalized with N,N‐dimethyl pyrrolidinium iodide, is found to be efficiently taken up by the cyanobacterium Synechocystis sp. PCC 6803. The distribution of this fullerene derivative near the thylakoid membrane, as well as site‐specific inhibitor assays and transient absorption spectroscopy, suggest that it can directly interact with the redox centers in the PETCs, particularly the acceptor side of photosystem I (PSI). The internalized fullerene derivatives facilitate the extraction of photosynthetic electrons and significantly enhance the photocurrent density of Synechocystis by approximately tenfold. This work opens up new possibility for the application of fullerenes as an excellent 3D electron carrier in living biophotovoltaics.

Abstract Background Observational studies have suggested the potential associations between atopic dermatitis (AD) and psychiatric disorders. However, the causal relationship between them remains uncertain. This study aimed to evaluate the potential bidirectional causal relationship between AD and psychiatric disorders, including autism spectrum disorder (ASD), major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), anorexia nervosa (AN), Tourette syndrome (TS), schizophrenia, and anxiety. Methods Bidirectional two-sample Mendelian randomization (MR) was employed to elucidate the causality between AD and psychiatric disorders, using summary statistics from the most comprehensive genome-wide association studies conducted on AD (Ncases = 60,653, Ncontrols = 804,329). Psychiatric disorders were derived from the Psychiatric Genomics Consortium and were independent of AD data sources. The MR analysis entailed the implementation of multiple methods, including the inverse variance weighted method, MR-Egger regression method, weighted median method, simple mode method, and weighted mode method. Results Bidirectional two-sample MR analysis uncovered significant causal associations between AD and severe psychiatric disorders. Specifically, liability to AD was associated with increased risk of ADHD (OR = 1.116; 95% CI: [1.009, 1.234]; P = 0.033) and ASD (OR = 1.131; 95% CI: [1.023, 1.251]; P = 0.016). Additionally, evidence suggested that liability to ADHD (OR = 1.112; 95% CI: [1.094, 1.130]; P = 9.20e-40), liability to AN (OR = 1.1; 95% CI: [1.068, 1.134]; P = 4.45e-10) and liability to BD (OR = 1.067; 95% CI: [1.009, 1.128]; P = 0.023) were associated with an increased risk of AD. Only the causal association between AD and ASD was independent of the reverse effect bias. These causal associations were robust and not affected by biases of heterogeneity and horizontal pleiotropy. Conclusions Our study emphasizes the significant causal association between AD and an increased risk of ASD, and also identifying BD and AN as risk factors for AD.

Under conditions of partial shadowing, traditional Maximum Power Point Tracking (MPPT) algorithms face difficulties in precisely locating the maximum power point (MPP) of the system. To address this problem, this paper proposes an optimization algorithm, Ant-Fuzzy Optimization (AFO) algorithm. AFO utilizes the global search capability of the ant colony optimization (ACO) algorithm and the high precision performance of the fuzzy logic (FL) algorithm, mitigating the tendency of the fuzzy algorithm to fall into local optima in shadow conditions. Internally, the AFO algorithm comprises two parallel logics, selecting different strategies for tracking based on varying environmental states, achieving a balance between tracking accuracy and computational efficiency. This intelligent logic selection mechanism allows the algorithm to flexibly adapt to diverse working environments of photovoltaic (PV) arrays, enhancing the robustness and adaptability of the system. The paper establishes corresponding simulation models in MATLAB/SIMULINK and validates AFO through hardware experiments on the dSPACE real-time simulation system. The results demonstrate the feasibility and effectiveness of AFO in practical environments. Both simulation and experimental prototypes indicate that AFO can rapidly and accurately extract the maximum power point with an accuracy of 98.7%. Furthermore, AFO exhibits rapid dynamic response characteristics, reaching steady state within 0.9 seconds, providing a reliable solution for optimizing the output power of photovoltaic arrays.

A class of dielectric filtering inverted-L antenna with reflective- and quasi-reflectionless-type radiation nulls is proposed to achieve wideband or dual-band operation. To this aim, a dual-function dissipative branch is exploited, which is in-parallel loaded at the feedline of the microstrip-fed dielectric inverted-L antenna. This absorptive branch, which is terminated in a grounded resistor, exhibits a quasi-complementary frequency response with regard to the one of the antenna. In this manner, it can mostly absorb the out-of-band RF-signal power not radiated by the antenna, hence creating quasi-reflectionless-type radiation nulls. Furthermore, the loaded branch can also generate a notch band giving rise to a reflective-type radiation null, which comes determined by the length of the branch and it is independent of the quasi-reflectionless radiation nulls. Thus, by controlling the spectral location of the notch band out of or within the operational frequency band of the dielectric inverted-L antenna, wideband or dual-band operational capabilities can be functionalized into it. For experimental-validation purposes, proof-of-concept prototypes for the two devised wideband and dual-band antenna approaches are designed, manufactured, and characterized. The measured results are in reasonably-close agreement with the simulated ones. The measured fractional impedance bandwidths of the two antenna prototypes are 28.3% (wideband one), 3.1% and 4.2% (dual-band one), respectively.

Abstract Background Methanomassiliicoccales are a recently identified order of methanogens that are diverse across global environments particularly the gastrointestinal tracts of animals; however, their metabolic capacities are defined via a limited number of cultured strains. Results Here, we profile and analyze 243 Methanomassiliicoccales genomes assembled from cultured representatives and uncultured metagenomes recovered from various biomes, including the gastrointestinal tracts of different animal species. Our analyses reveal the presence of numerous undefined genera and genetic variability in metabolic capabilities within Methanomassiliicoccales lineages, which is essential for adaptation to their ecological niches. In particular, gastrointestinal tract Methanomassiliicoccales demonstrate the presence of co-diversified members with their hosts over evolutionary timescales and likely originated in the natural environment. We highlight the presence of diverse clades of vitamin transporter BtuC proteins that distinguish Methanomassiliicoccales from other archaeal orders and likely provide a competitive advantage in efficiently handling B12. Furthermore, genome-centric metatranscriptomic analysis of ruminants with varying methane yields reveal elevated expression of select Methanomassiliicoccales genera in low methane animals and suggest that B12 exchanges could enable them to occupy ecological niches that possibly alter the direction of H2 utilization. Conclusions We provide a comprehensive and updated account of divergent Methanomassiliicoccales lineages, drawing from numerous uncultured genomes obtained from various habitats. We also highlight their unique metabolic capabilities involving B12, which could serve as promising targets for mitigating ruminant methane emissions by altering H2 flow.

Background: The lifestyles of preschoolers have become physically inactive and sedentary, their eating habits unhealthy, and their sleep routines increasingly disturbed. Parental involvement appears crucial to combat the unhealthy lifestyle of preschoolers. Because of the recognized barriers to traditional face-to-face interventions, easy access and lower costs make electronic health (eHealth) interventions appealing. However, whether parent-based eHealth intervention may be harnessed to improve the aforementioned lifestyle behaviors of preschoolers is currently unclear, a gap that this systematic review intends to address. This study aims to systematically review the current literature concerning the effectiveness of parent-based eHealth intervention on the physical activity, dietary behaviors, and sleep of preschoolers. Method: This systematic review conforms to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Six databases (EMBASE, PubMed, MEDLINE, Web of Science, SPORTDiscus, and PsycINFO) were retrieved for the period from January 2000 to December 2022. Studies were eligible if 1 they were quantitative study design; 2 eHealth interventions in which parents were the change agents targeted children aged 3–6 years; 3 interventions examined the effectiveness of eHealth or incorporated eHealth as one of the intervention modalities; 4 at least one variable included in either primary or secondary outcome had to concentrate on the physical activity, diet, and sleep of preschoolers; 5 publication type was limited to the English language and peer-reviewed journal articles; 6 study settings were confined to family- or parent-based ones. The risk of bias was assessed, based upon Version 2 of the Cochrane risk-of-tool for randomized trials (RoB2). Results: Twelve studies were screened. No significant group-by-time improvement in physical activity was found in studies related to physical activity outcomes. Two studies reported a significant difference between groups concerning motor ability, with one study indicating improved object control with the other reporting improvement in both object control and locomotor skills. Of the studies related to dietary behavior outcomes, six studies reported a significant difference at the posttest compared to the control group, in terms of vegetable and fruit intake, sugar-sweetened drinks, reduced candy consumption, and improved non-core food. Three studies reported a significant difference between groups in sleep duration at the end of the posttest, with the result of one study limited to preference-only participants. None of the reviewed studies found a significant difference between groups for sleep problems. Conclusion: Parent-based eHealth interventions were not significantly effective in improving physical activity and reducing sleep problems in preschoolers, but the majority of studies have found that this type of intervention significantly improves the dietary behaviors and sleep duration of preschoolers. High-quality, robustly designed studies to balance the intervention dosage and sequence are needed to investigate the effectiveness of parent-based eHealth intervention on physical activity, dietary behaviors, and sleep in preschoolers, particularly those raised in other cultural background, which may significantly impact their lifestyle. Trial registration: International Prospective Register of Systematic Review (PROSPERO): CRD42023418861.

Abstract Background It is a very rare form of ocular motility characterized by alternating strabismus and orthotropia. We report a patient with a 48-h cycle of esohypotropia associated with axial high myopia that resolved by Yokoyama procedure. Case presentation A 43-year-old female patient who underwent left medial rectus muscle recession and lateral rectus muscle resection elsewhere due to highly myopic strabismus 2 years ago. The patient experienced a recurrence of left esohypotropia 12 months after undergoing surgery, exhibiting a 48-hour cycle. The cycle is one full day of esohypotropia and one day of orthotropia. The patient exhibited a case of high myopia in the left eye, characterized by a diopter measurement of -24.00DS and an eye axis measurement of 28.43 mm. Orbital CT showed supertemporal dislocation of the posterior portion of the elongated globe out from the muscle cone. Based on these observations, we performed Yokoyama procedure by uniting the muscle bellies of the superior rectus(SR) and lateral rectus (LR) muscles to restoring the dislocated globe back into the muscle cone. Conclusions When cyclic strabismus is combined with axial high myopia, the Yokoyama procedure was effective and cycles are successfully terminated without overcorrection on no squint days. The purpose of this procedure is to put the dislocated globe back into its muscle cone by uniting the muscle bellies of the superior rectus and lateral rectus.

Ethylene-insensitive 3/Ethylene-insensitive3-like proteins (EIN3/EIL) represent a group of transcription factors critical for the ethylene signaling transduction that manipulate downstream ethylene-responsive genes, thereby regulating plant growth, development, and stress responses. However, the identification, evolution, and divergence of the EIL family remain to be studied in Sorghum bicolor. Here, we identified eight SbEILs, which were expanded due to whole-genome-duplication (WGD) events. Characterization of the protein sequences and expression atlas demonstrates that the WGD-duplicated SbEILs could become divergent due to the differential expression patterns, rather than domain and motif architectures. Comparative expression analysis was performed between the RNA-seq data sets of internodes from several sorghum cultivars to understand the potential roles of SbEIL members in internode elongation and maturation. Our results identified SbEIL3 and 7 (the latter as a homolog of OsEIL7/OsEIL1) to be the highly expressed SbEIL genes in sorghum internodes and revealed a potential functional link between SbEIL7 and internode maturation. The co-expression analysis and comparative expression analysis with ethylene-regulated gene sets found that SbEIL7 was co-regulated with a set of ubiquitin-related protein degradation genes, suggesting possible involvement of SbEIL7 in protein degradation and processing during the post-anthesis stages. Altogether, our findings lay a foundation for future functional studies of ethylene signaling-mediated gene regulation and improvement of sorghum internode development.

Growth-regulating factor (GRF) is a plant-specific family of transcription factors crucial for meristem development and plant growth. Sorghum (Sorghum bicolor L. Moench) is a cereal species widely used for food, feed and fuel. While sorghum stems are important biomass components, the regulation of stem development and the carbohydrate composition of the stem tissues remain largely unknown. Here, we identified 11 SbGRF-encoding genes and found the SbGRF expansion driven by whole-genome duplication events. By comparative analyses of GRFs between rice and sorghum, we demonstrated the divergence of whole-genome duplication (WGD)-derived OsGRFs and SbGRFs. A comparison of SbGRFs’ expression profiles supports that the WGD-duplicated OsGRFs and SbGRFs experienced distinct evolutionary trajectories, possibly leading to diverged functions. RNA-seq analysis of the internode tissues identified several SbGRFs involved in internode elongation, maturation and cell wall metabolism. We constructed co-expression networks with the RNA-seq data of sorghum internodes. Network analysis discovered that SbGRF1, 5 and 7 could be involved in the down-regulation of the biosynthesis of cell wall components, while SbGRF4, 6, 8 and 9 could be associated with the regulation of cell wall loosening, reassembly and/or starch biosynthesis. In summary, our genome-wide analysis of SbGRFs reveals the distinct evolutionary trajectories of WGD-derived SbGRF pairs. Importantly, expression analyses highlight previously unknown functions of several SbGRFs in internode elongation, maturation and the potential involvement in the metabolism of the cell wall and starch during post-anthesis stages.

Background: Whole-colon examination is crucial for patients with gynecologic oncology, which somehow presents challenges in some cases. This study is aiming to investigate the effectiveness of gastroscope applied in difficult colonoscopy among such patients. Methods: Patients with gynecologic oncology who underwent colon examination were assessed and categorized into two groups, gastroscope replacement group (GR-group) and normal colonoscopy group (NC-group). Gastroscope was applied in the challenging cases within GR-group following unsuccessful attempts for colonoscopy. The assessment encompassed various features, including body mass index (BMI), nutritional indicators, previous therapeutic history, and the number and size of gynecologic oncology. A multivariate analysis was performed to screen out high-risk features for difficult colonoscopy, and a model was developed to evaluate the appropriateness of gastroscope application in such instances. Decision curve analysis was conducted to evaluate the clinical usefulness of the model. Results: We retrospectively collected the clinical characteristics of 171 patients with gynecologic oncology who underwent colon examinations, with 19 cases and 20 cases of difficult colonoscopy in GR-group and NC-group, respectively. The success rate of passing through the narrow site was 63% for the GR-group and 60% for the NC-group (p = 1.000). High risk factors of difficult colonoscopy included a BMI ≤18 kg/m2 (p = 0.03) and post-treatment status (p < 0.01). The evaluation model, constructed from clinical features, demonstrated excellent discrimination with an area under curve (AUC) of 0.86, offering significant net benefits to the validation group. Conclusions: A low BMI and post-treatment status emerged as independent risk factors for difficult colonoscopy in patients with gynecologic oncology. In such cases, gastroscope proved to be an effective and reliable alternative for the colon examination. The current findings are promising to be put into clinical use after verification by large-scale prospective studies.

Recent Byzantine Fault-Tolerant (BFT) State Machine Replication (SMR) protocols increasingly focus on scalability and security to meet the growing demand for Distributed Ledger Technology (DLT) applications across various domains. Current BFT consensus algorithms typically require a single leader node to receive and validate votes from the majority process and broadcast the results, a design challenging to scale in large systems. We propose a fast-response consensus algorithm based on improvements to HotStuff, aimed at enhancing transaction ordering speed and overall performance of distributed systems, even in the presence of faulty copies. The algorithm introduces an optimistic response assumption, employs a message aggregation tree to collect and validate votes, and uses a dynamically adjusted threshold mechanism to reduce communication delay and improve message delivery reliability. Additionally, a dynamic channel mechanism and an asynchronous leader multi-round mechanism are introduced to address multiple points of failure in the message aggregation tree structure, minimizing dependence on a single leader. This adaptation can be flexibly applied to real-world system conditions to improve performance and responsiveness. We conduct experimental evaluations to verify the algorithm’s effectiveness and superiority. Compared to the traditional HotStuff algorithm, the improved algorithm demonstrates higher efficiency and faster response times in handling faulty copies and transaction ordering.

Background: Although n-3 Polyunsaturated fatty acids (PUFAs) may benefit cognitive performance, the association of n-3 PUFA intake with dementia risk under dysglycemia has not been examined. We aimed to evaluate the relationship between fish oil supplement use or fish consumption and dementia risk among older patients with diabetes. Method: A total of 16,061 diabetic patients aged over 60 years were followed up in the UK Biobank. Fish oil supplements use (yes or no) was collected by the touch screen questionnaire. The diagnosis of dementia was ascertained by the UK Biobank Outcome Adjudication Group. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. Results: A total of 337 cases of dementia were confirmed after a mean duration of 7.7 years (123,486 person-years) of follow-up. Habitual use of fish oil supplements showed a 24% lower dementia risk among older diabetic patients [HRs (95% CIs): 0.76 (0.60−0.98) (P = 0.031)] compared with non-users. Such inverse association was not modified by the APOE ε4 genotype. However, the consumption of both oily fish (≥2 times/week) and non-oily fish (≥2 times/week) had no significant association with dementia risk (p-trend = 0.271 and p-trend = 0.065) compared with non-consumers. Conclusion: In summary, fish oil supplementation may play a protective role in cognitive function across all APOE genotypes, while non-oily fish and oily fish consumption have no protective association among older diabetic patients.

Atypical Chronic Myeloid Leukemia (aCML), a myeloproliferative neoplasm with poor prognosis, was reclassified as aCML by the ICC classification, and as MDS/MPN with neutrophilia by the WHO 2022 classification. Due to the heterogeneity of its clinical features and the lack of unique biomarkers, as well as limited treatment options, aCML currently lacks a standardized treatment protocol. In this case report, we reviewed a young man diagnosed with aCML who achieved complete clinical and hematologic remission subsequent to receiving a therapeutic regimen combining Venetoclax and Azacitidine.

Abstract Objective To explore whether the upper and/or middle mediastinal nodes (UMMN) should be dissected in Siewert type II adenocarcinoma (AC) according to the incidence of lymph node metastasis. Additionally, to investigate the association between the length of esophageal involvement (LEI) and the UMMN metastases. Methods A cohort with Siewert type II AC who were operated on by a surgical team that routinely treated esophagogastric junction (EGJ) tumors with esophagectomy and extended lymphadenectomy were assessed retrospectively. The primary endpoint of the research was the metastasis rate of UMMN. Results A total of 94 patients with EGJ tumor from July 2018 to September 2022 were enrolled. Station 106recR (6.4%, 6/94) was the only station among upper mediastinal nodes (UMN) that presented positive nodes. Middle mediastinal nodes (MMN) metastases of station 107, 109 and station 108 were 2.1% (2/94) and 5.0% (4/80), respectively. Among the 11 patients with MMN or UMN metastases, 63.6% (7/11) had lesser than seven metastatic nodes, and 54.5% (6/11) had a pathological N stage ≤2. LEI >3 cm (p = 0.042) showed a higher risk for MMN metastases in univariable logistic analysis. However, no independent risk factor for mediastinal node metastases was detected. Conclusion This study demonstrated that the incidence of positive MMN and UMN is relatively low in resectable Siewert type II AC, which indicated that it is not necessary to perform a routine dissection upon these stations. LEI >3 cm might be associated with higher risk for mediastinal node metastasis. Certain patients could benefit from extended lymphadenectomy since most of the patients with positive MMN or UMN have a limited number of metastatic nodes.

Abstract Background The efficacy and safety of the novel immunotherapy method, intra‐cervical lymphatic immunotherapy (ICLIT), need to be investigated. Comparing it with subcutaneous immunotherapy (SCIT), we clarified the long‐term efficacy and safety of intra‐cervical lymphatic immunotherapy on allergic rhinitis (AR), and investigated the improvement of clinical efficacy of the booster injection at 1 year after ICLIT treatment. Methods Ninety adult patients with dust mite allergy were randomly divided into 3 groups: 30 in the SCIT group, 30 in the ILCLIT group, and 30 in ICLIT booster group. Changes in total symptom score (TSS), nasal symptom score (TNSS), ocular symptom score (TOSS) and total medication score (TMS) were evaluated in the three groups. Adverse reactions were recorded, and serum dust mite specific IgE (sIgE) and specific IgG4 were assessed in the ICLIT group and ICLIT booster group. Results TSS, TNSS, TOSS, and TMS scores were significantly lower in the three groups at 36 months after treatment (p

This paper examines the future of maker education through an analysis of feedback from judges in the China-U.S. Young Maker Competition. Drawing on inputs from 36 judges from diverse backgrounds in academia, industry, and sponsoring companies, the study uses thematic analysis of interviews, feedback, and focus group discussions to uncover key educational trends. It highlights critical themes such as transdisciplinary creativity, real-world application, sustainability, cross-cultural collaboration, and innovation mindset. The research reveals a trend towards integrating various academic fields to boost creative problem-solving and application in real-life scenarios. Sustainability is identified as a crucial component, pointing to the need for environmentally aware education. The study also emphasizes the importance of cross-cultural collaboration for global interconnectedness and adaptive problem-solving, alongside fostering a continuous innovation mindset in students. Concluding with future directions for maker education, the paper advocates for an experiential, inclusive, and forward-looking educational approach. It underscores the importance of a broad curriculum that integrates entrepreneurial skills, promotes lifelong learning, and enhances global connectivity. This study provides insights for educators, policymakers, and practitioners, offering a streamlined roadmap for advancing maker education in a rapidly evolving global context.

Fibrotic hypersensitivity pneumonitis (FHP) is a fatal interstitial pulmonary disease with limited treatment options. Lung macrophages are a heterogeneous cell population that exhibit distinct subsets with divergent functions, playing pivotal roles in the progression of pulmonary fibrosis. However, the specific macrophage subpopulations and underlying mechanisms involved in the disease remain largely unexplored. In this study, a decision tree model showed that matrix metalloproteinase-14 (MMP14) had higher scores for important features in the up-regulated genes in macrophages from mice exposed to the Saccharopolyspora rectivirgula antigen (SR-Ag). Using single-cell RNA sequencing (scRNA-seq) analysis of hypersensitivity pneumonitis (HP) mice profiles, we identified MMP14high macrophage subcluster with a predominant M2 phenotype that exhibited higher activity in promoting fibroblast-to myofibroblast transition (FMT). We demonstrated that suppressing toll-like receptor 2 (TLR2) and nuclear factor kappa-B (NF-κB) could attenuate MMP14 expression and exosome secretion in macrophages stimulation with SR-Ag. The exosomes derived from MMP14-overexpressing macrophages were found to be more effective in regulating the transition of fibroblasts through exosomal MMP14. Importantly, it was observed that the transfer of MMP14-overexpressing macrophages into mice promoted lung inflammation and fibrosis induced by SR-Ag. NSC-405020 binding to the hemopexin domain (PEX) of MMP-14 ameliorated lung inflammation and fibrosis induced by SR-Ag in mice. Thus, MMP14-overexpressing macrophages may be an important mechanism contributing to the exacerbation of allergic reactions. Our results indicated that MMP14 in macrophages has the potential to be a therapeutic target for HP.

Abstract Background The FLT3/ITD mutation exists in many acute myeloid leukemia (AML) patients and is related to the poor prognosis of patients. In this study, we attempted to evaluate the antitumor activity of simvastatin, a member of the statin class of drugs, in vitro and in vivo models of FLT3/ITD AML and to identify the potential mechanisms. Methods Cell Counting Kit-8 (CCK-8) and Annexin V/propidium iodide (PI) staining kits were used to detect cell viability and apoptosis, respectively. Subsequently, Western blot and rescue experiment were applied to explore the potential molecular mechanism. In vivo anti-leukemia activity of simvastatin was evaluated in xenograft mouse models. Results In vitro experiments revealed that simvastatin inhibited AML progression in a dose- and time-dependent manner, while in vivo experiments showed that simvastatin significantly reduced tumor burden in FLT3/ITD xenograft mouse models. After simvastatin treatment of FLT3/ITD AML cells, intracellular Rap1 was downregulated and the phosphorylation levels of its downstream targets MEK, ERK and p38 were significantly inhibited. The rescue experiment showed that mevalonate, an intermediate product of the metabolic pathway of mevalonate, and its downstream geranylgeranyl pyrophosphate (GGPP) played a key role in this process. Finally, we demonstrate that simvastatin can induce apoptosis of primary AML cells, while having no effect on peripheral blood mononuclear cells from normal donors. Conclusions Simvastatin can selectively and effectively eradicate FLT3/ITD AML cells in vitro and in vivo, and its mechanism may be related to the disruption of the HMG-CoA reductase pathway and the downregulation of the MEK/ERK and p38-MAPK signaling pathways.

Abstract The delivery of dermatology services has undergone dramatic changes in the past century. The goals and timelines of care have evolved as have the diagnostic and therapeutic tools, resulting in the need to capture and manage information differently, both qualitatively and quantitatively. The predominant and basic office-based ambulatory care model has remained relatively unchanged. Patients and providers interact with minimal pre-visit preparation using the “agenda-less” meeting model. This care model is ill-suited to manage the vastly expanded data capture and processing requirement of twenty-first century dermatology. We have developed novel tools to automate pre-visit data collection which allows for more robust information capture which moves data capture outside of the time-constrained clinic visit. These tools capture structured data, integrate into electronic health records, and create summary reports in real time to assist decision-making. These tools, if scaled, can facilitate the information management needs of dermatology care.

Abstract Background The anatomical infiltrated brain area and the boundaries of gliomas have a significant impact on clinical decision making and available treatment options. Identifying glioma-infiltrated brain areas and delineating the tumor manually is a laborious and time-intensive process. Previous deep learning-based studies have mainly been focused on automatic tumor segmentation or predicting genetic/histological features. However, few studies have specifically addressed the identification of infiltrated brain areas. To bridge this gap, we aim to develop a model that can simultaneously identify infiltrated brain areas and perform accurate segmentation of gliomas. Methods We have developed a transformer-based multi-task deep learning model that can perform two tasks simultaneously: identifying infiltrated brain areas segmentation of gliomas. The multi-task model leverages shaped location and boundary information to enhance the performance of both tasks. Our retrospective study involved 354 glioma patients (grades II-IV) with single or multiple brain area infiltrations, which were divided into training (N = 270), validation (N = 30), and independent test (N = 54) sets. We evaluated the predictive performance using the area under the receiver operating characteristic curve (AUC) and Dice scores. Results Our multi-task model achieved impressive results in the independent test set, with an AUC of 94.95% (95% CI, 91.78–97.58), a sensitivity of 87.67%, a specificity of 87.31%, and accuracy of 87.41%. Specifically, for grade II-IV glioma, the model achieved AUCs of 95.25% (95% CI, 91.09–98.23, 84.38% sensitivity, 89.04% specificity, 87.62% accuracy), 98.26% (95% CI, 95.22–100, 93.75% sensitivity, 98.15% specificity, 97.14% accuracy), and 93.83% (95%CI, 86.57–99.12, 92.00% sensitivity, 85.71% specificity, 87.37% accuracy) respectively for the identification of infiltrated brain areas. Moreover, our model achieved a mean Dice score of 87.60% for the whole tumor segmentation. Conclusions Experimental results show that our multi-task model achieved superior performance and outperformed the state-of-the-art methods. The impressive performance demonstrates the potential of our work as an innovative solution for identifying tumor-infiltrated brain areas and suggests that it can be a practical tool for supporting clinical decision making.

Esophageal cancer (EC) is particularly common in China. With the continuing progress of multi-disciplinary therapy including early screening, minimally invasive techniques, radiotherapy and chemotherapy, the 5-year survival of EC has been improved in China. However, there are considerable disparities in the diagnosis and treatment quality among different regions. The Esophageal Cancer Expert Committee of the National Cancer Quality Control Center (NCQCC) considers a set of authoritative quality control standards as an opportunity to eliminate the disparities and improve the overall survival and quality of life of EC. To further promote the quality control for standardized diagnosis and treatment of EC, the National Cancer Center commissioned the Esophageal Cancer Quality Control Expert Committee to draft and formulate the Chinese Quality Control Indices for Standardized Diagnosis and Treatment of Esophageal Cancer (2022 edition). The Indices includes 21 items that cover all key areas in the diagnosis and treatment of esophageal cancer, such as medical oncology, radiation oncology, endoscopy, and pathology.

Auxin Response Factors (ARFs) make up a plant-specific transcription factor family that mainly couples perception of the phytohormone, auxin, and gene expression programs and plays an important and multi-faceted role during plant growth and development. Lemongrass (Cymbopogon flexuosus) is a representative Cymbopogon species widely used in gardening, beverages, fragrances, traditional medicine, and heavy metal phytoremediation. Biomass yield is an important trait for several agro-economic purposes of lemongrass, such as landscaping, essential oil production, and phytoremediation. Therefore, we performed gene mining of CfARFs and identified 26 and 27 CfARF-encoding genes in each of the haplotype genomes of lemongrass, respectively. Phylogenetic and domain architecture analyses showed that CfARFs can be divided into four groups, among which groups 1, 2, and 3 correspond to activator, repressor, and ETTN-like ARFs, respectively. To identify the CfARFs that may play major roles during the growth of lemongrass plants, RNA-seq was performed on three tissues (leaf, stem, and root) and four developmental stages (3-leaf, 4-leaf, 5-leaf. and mature stages). The expression profiling of CfARFs identified several highly expressed activator and repressor CfARFs and three CfARFs (CfARF3, 18, and 35) with gradually increased levels during leaf growth. Haplotype-resolved transcriptome analysis revealed that biallelic expression dominance is frequent among CfARFs and contributes to their gene expression patterns. In addition, co-expression network analysis identified the modules enriched with CfARFs. By establishing orthologous relationships among CfARFs, sorghum ARFs, and maize ARFs, we showed that CfARFs were mainly expanded by whole-genome duplications, and that the duplicated CfARFs might have been divergent due to differential expression and variations in domains and motifs. Our work provides a detailed catalog of CfARFs in lemongrass, representing a first step toward characterizing CfARF functions, and may be useful in molecular breeding to enhance lemongrass plant growth.