Search

Abstract In order to figure out actual shaft resistance, axial forces of pile shaft have to be calculated based on strain test, which is a challenge for heat and steam cured prestressed high-strength concrete pipe piles. Disadvantages of three common methods of strain test and the empirical linear equation between axial force and strain are analyzed. A new strain test method, namely the slot-forming wood method, is proposed and applied in laboratory and field test. Taking pipe pile PHC500AB-125 as an example, laboratory tests were performed to establish the nonlinear function between axial force and strain. Field tests were performed and strains were tested by the slot-forming wood method. Results calculated by the nonlinear function between axial force and strain were compared with that by traditional linear equation to reveal the difference. The tests indicated that the new method of strain test was applicable and useful since the survival rate of strain gauges was high and the accuracy has been improved. Overcoming the disadvantages of the traditional linear equation, the proposed function between axial force and strain is more accurate. The study provides theoretical basis for technology innovation in pile test and for revision of related technical standards.

Abstract Background This study aimed to compare the diagnostic efficacy of Two-dimensional shear wave elastography (2D-SWE) with that of transient elastography (TE) in predicting the risk of esophagogastric varices and histological staging in patients with primary biliary cholangitis (PBC). Methods This single-center prospective study enrolled the patients with PBC diagnosed by liver biopsy following 2D-SWE and TE. Receiver operating characteristic (ROC) curves were constructed for SWE-liver stiffness measurement (LSM) and TE-LSM to assess their diagnostic efficacy for histological staging ≥ stage 2, ≥ stage 3, and = stage 4. The diagnostic efficacy and accuracy of SWE-LSM were compared with those of the Baveno VI criteria for detecting esophagogastric varices. Additionally, the impact of different laboratory parameters on SWE-LSM was analyzed. Results We evaluated 77 patients (median age, 52 years (range: 16 − 75 years), 66 females). ROC curves constructed using TE-LSM and SWE-LSM demonstrated similar diagnostic efficacy for histological staging ≥ stage 2 (area under the curve [AUC]: 0.824 vs. 0.823 for TE-LSM and SWE-LSM, respectively, p = 0.9764), ≥ stage 3 (AUC: 0.918 vs. 0.907 for TE-LSM and SWE-LSM, respectively, p = 0.6443), and = stage 4 (AUC: 0.907 vs. 0.902 for TE-LSM and SWE-LSM, respectively, p = 0.8763). Additionally, while there was no significant difference in the diagnostic efficacy between the two methods for detecting esophagogastric varices (Z = 1.516, p = 0.1296), 2D-SWE had a slightly higher diagnostic accuracy than TE (61.8% vs. 76.4%). Transaminases and bilirubin levels had little influence on SWE-LSM. Conclusion 2D-SWE exhibited comparable performance to TE in predicting the risk of esophagogastric varices and histological staging.

Abstract Toxins of toxin-antitoxin systems use diverse mechanisms to inhibit bacterial growth. In this study, we characterize the translation inhibitor toxin MenT3 of Mycobacterium tuberculosis, the bacterium responsible for tuberculosis in humans. We show that MenT3 is a robust cytidine specific tRNA nucleotidyltransferase in vitro, capable of modifying the aminoacyl acceptor ends of most tRNA but with a marked preference for tRNASer, to which long stretches of cytidines are added. Furthermore, transcriptomic-wide analysis of MenT3 targets in M. tuberculosis identifies tRNASer as the sole target of MenT3 and reveals significant detoxification attempts by the essential CCA-adding enzyme PcnA in response to MenT3. Finally, under physiological conditions, only in the presence the native menAT3 operon, an active pool of endogenous MenT3 targeting tRNASer in M. tuberculosis is detected, likely reflecting the importance of MenT3 during infection.

Abstract Tamoxifen (TAM) resistance is a major challenge in treating oestrogen receptor-positive (ER+) breast cancers. It is possible that the H2S synthase cystathionine-γ-lyase (CSE), which has been previously shown to promote tumour growth and metastasis in other cancer cells, is involved in this resistance. Therefore, we investigated CSE's role and potential mechanisms in TAM-resistant breast cancer cells. First, we examined the effect of CSE expression on TAM sensitivity and resistance in MCF7 (breast cancer) cells. The findings revealed that CSE was directly associated with TAM sensitivity and involved in TAM resistance in ER+ breast cancer cells, indicating that it may be useful as a biomarker. Next, we wanted to determine the molecular mechanism of CSE's role in TAM resistance. Using cell migration, co-immunoprecipitation, western blotting, and cell viability assays, we determined that the CSE/H2S system can affect the expression of PPARγ by promoting the sulfhydrylation of PPARγ, which regulates the transcriptional activity of ACSL1. ACSL1, in turn, influences STAT3 activation by affecting the phosphorylation, palmitoylation and dimerization of STAT3, ultimately leading to the development of TAM resistance in breast cancer. Finally, we examined the effect of CSE inhibitors on reducing drug resistance to determine whether CSE may be used as a biomarker of TAM resistance. We observed that the novel CSE inhibitor I194496 can reverse TAM resistance in TAM-resistant breast cancer via targeting the PPARγ/ACSL1/STAT3 signalling pathway. Overall, our data indicate that CSE may serve as a biomarker of TAM resistance and that the CSE inhibitor I194496 is a promising candidate for combating TAM resistance.

Abstract Background This multi-center cohort study aimed to investigate whether sex and prediagnosis lifestyle affect the prognosis of gastric cancer. Methods Patients with gastric cancer were from four gastric cancer cohorts of the National Cancer Center of China, The First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Provincial Cancer Hospital. Prediagnosis lifestyle factors in our study included body mass index (BMI) at diagnosis, usual BMI, weight loss, the history of Helicobacter pylori (Hp) infection, and the status of smoking and drinking. Results Four gastric cancer cohorts with 29,779 gastric cancer patients were included. In total patients, female patients had a better prognosis than male patients (HR = 0.938, 95%CI: 0.881–0.999, P = 0.046). For prediagnosis lifestyle factors, BMI at diagnosis, usual BMI and the amount of smoking were statistically associated with the prognosis of gastric cancer patients. Female patients with smoking history had a poorer survival than non-smoking females (HR = 0.782, 95%CI: 0.616–0.993, P = 0.044). Tobacco consumption > 40 cigarettes per day (HR = 1.182, 95%CI: 1.035–1.350, P = 0.013) was independent adverse prognostic factors in male patients. Obesity paradox was observed only in male patients (BMI

Abstract Stepping movement is delta (1–4 Hz) rhythmic and depends on sensory inputs. Stepping-related delta-rhythmic neural activity is coupled to beta (10–30 Hz) frequency dynamics that are also prominent in sensorimotor circuits. We explored how beta-frequency sensory stimulation influences stepping and dorsal striatal regulation of stepping. We delivered audiovisual stimulation at 10 or 145 Hz to mice voluntarily locomoting, while recording locomotion, cellular calcium dynamics and local field potentials (LFPs). We found that 10 Hz, but not 145 Hz stimulation prominently entrained striatal LFPs. Even though stimulation at both frequencies promoted locomotion and desynchronized striatal network, only 10 Hz stimulation enhanced the delta rhythmicity of stepping and strengthened the coupling between stepping and striatal LFP delta and beta oscillations. These results demonstrate that higher frequency sensory stimulation can modulate lower frequency striatal neural dynamics and improve stepping rhythmicity, highlighting the translational potential of non-invasive beta-frequency sensory stimulation for improving gait.

Abstract Objective To assess the immunization efficacy and incidence of adverse reactions after hepatitis B vaccination in children with thalassemia based on data from real-world studies. Methods A total of 625 children were recruited into this cross-sectional study. Subgroup analyses of different thalassemia types were performed using binary logistic regression, the factors affecting HBsAb levels were identified using multiple linear regression, and the dose-response relationship between the duration of immunization and seroconversion was explored using the restricted cubic spline (RCS) model to further assess the protective duration of the hepatitis B vaccine. Results HBsAb positivity in enrolled children was 87.3% in the thalassemia group and 81.4% in the control group. Multifactorial analysis revealed that the duration of immunization, age at completion of vaccination, and whether the first dose was delayed were significant factors influencing HBsAb levels in children (P

Abstract Background Gastric cancer is a major health problem worldwide, with a high incidence among older adults. Given the aging overall population, it was crucial to understand the current burden and prospective trend of older gastric cancer. This study aimed to analyze the temporal trends of the incidence, mortality, and survival of older gastric cancer in the highest gastric cancer risk area in China from 2010 to 2019, and to predict the future burden of older gastric cancer up to 2024. Methods The study was conducted in Gansu province, an area characterized by the highest gastric cancer incidence and mortality in China. The registration data of gastric cancer incidence and mortality from 2010 to 2019 were pooled from registries in the Gansu Cancer Registration System, while survival data were collected from the First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Cancer Hospital. Chinese standard population in 2000 and the Segi’s world standard population were applied to calculate the age-standardized rate. Joinpoint regression was used to analyze the average annual percentage change (AAPC) in cancer incidence and mortality. Autoregressive Integrated Moving Average (ARIMA) models were employed to generate forecasts for incidence and mortality from 2020 to 2024. Results Based on registry data from 2010 to 2019, the incidence and mortality rates of gastric cancer among older adults remained stable. The incidence rates declined from 439.65 per 100,000 in 2010 to 330.40 per 100,000 in 2019, with an AAPC of -2.59% (95% confidence interval[CI], -5.14 to 0.04, P = 0.06). Similarly, the mortality rate changed from 366.98 per 100,000 in 2010 to 262.03 per 100,000 in 2019, with an AAPC of -2.55% (95% CI, -8.77–4.08%, P = 0.44). In the hospital-based cohort, the decline in survival rates was reported among older patients with gastric cancer in the highest gastric cancer risk area in China, with the 3-year overall survival (OS) decreasing from 58.5% (95% CI, 53.5–63.2%) in 2010 to 34.4% (95%CI, 32.1–36.7%) in 2019, and the 3-year progression-free survival (PFS) decreasing from 51.3% (95%CI, 47.5–55.1%) in 2010 to 34.2% (95%CI, 32.0–36.3%) in 2019, respectively. Moreover, forecasts generated by ARIMA models revealed a significant decline in the incidence and mortality of older gastric cancer in China from 2020 to 2024. Specifically, the incidence rate of older gastric cancer was expected to decrease from 317.94 per 100,000 population in 2020 to 205.59 per 100,000 population in 2024, while the anticipated mortality rate was estimated to decrease from 222.52 per 100,000 population in 2020 to 186.22 per 100,000 population in 2024. Conclusion From 2010 to 2019, the incidence and mortality of older gastric cancer remained stable in the highest gastric cancer risk area in China, while the survival rates showed a decline. Based on the ARIMA models, it was anticipated that there might be a continued decline in older gastric cancer incidence and mortality in the highest-risk area in China over the next five years.

The ever-growing energy demand and environmental issues have stimulated the development of sustainable energy technologies. Herein, an efficient and environmentally friendly electrochemical transformation technology was proposed to prepare highly graphitized carbon materials from an abundant natural resource - lignin (LG). The preparation process mainly includes pyrolytic carbonization of raw LG material and electrochemical conversion of amorphous carbon precursor. Interestingly, with the assistance of Co catalyst, the graphitization degree of the products was significantly improved, in which the mechanism was the removal of heteroatoms in LG and the rearrangement of carbon atoms into graphite lattice. Furthermore, tunable microstructures (nanoflakes) under catalytic effects could also be observed by controlling the electrolytic parameters. Compared with the products CN1 (without catalyst) and CN5 (with 10% catalyst), the specific surface area are 158.957 and 202.246 m2 g−1, respectively. When used as the electrode material for lithium-ion batteries, CN5 delivered a competitive specific capacity of ∼350 mAh g−1 (0.5 C) compared with commercial graphite. The strategy proposed in this work provides an effective way to extract value-added graphite materials from lignin and can be extended to the graphitization conversion of any other amorphous carbon precursor materials.

Abstract Background The oral administration of drugs for treating ulcerative colitis (UC) is hindered by several factors, including inadequate gastrointestinal stability, insufficient accumulation in colonic lesions, and uncontrolled drug release. Methods A multiple sensitive nano-delivery system comprising β-cyclodextrin (CD) and 4-(hydroxymethyl)phenylboronic acid (PAPE) with enzyme/reactive oxygen species (ROS) sensitivity was developed to load celastrol (Cel) as a comprehensive treatment for UC. Results Owing to the positive charge in the site of inflamed colonic mucosa, the negatively charged nanomedicine (Cel/NPs) could efficiently accumulate. Expectedly, Cel/NPs showed excellent localization ability to colon in vitro and in vivo tests. The elevated concentration of ROS and intestinal enzymes in the colon microenvironment quickly break the CD, resulting in Cel release partially to rebalance microbiota and recover the intestinal barrier. The accompanying cellular internalization of residual Cel/NPs, along with the high concentration of cellular ROS to trigger Cel burst release, could decrease the expression of inflammatory cytokines, inhibit colonic cell apoptosis, promote the macrophage polarization, scavenge ROS, and regulate the TLR4/NF-κB signaling pathway, which certified that Cel/NPs possessed a notably anti-UC therapy outcome. Conclusions We provide a promising strategy for addressing UC symptoms via an enzyme/ROS-sensitive oral platform capable of releasing drugs on demand. Graphical Abstract

Objective: Accurate prognosis prediction is critical for individualized-therapy making of gastric cancer patients. We aimed to develop and test 6-month, 1-, 2-, 3-, 5-, and 10-year overall survival (OS) and cancer-specific survival (CSS) prediction models for gastric cancer patients following gastrectomy. Methods: We derived and tested Survival Quilts, a machine learning-based model, to develop 6-month, 1-, 2-, 3-, 5-, and 10-year OS and CSS prediction models. Gastrectomy patients in the development set (n = 20,583) and the internal validation set (n = 5,106) were recruited from the Surveillance, Epidemiology, and End Results (SEER) database, while those in the external validation set (n = 6,352) were recruited from the China National Cancer Center Gastric Cancer (NCCGC) database. Furthermore, we selected gastrectomy patients without neoadjuvant therapy as a subgroup to train and test the prognostic models in order to keep the accuracy of tumor-node-metastasis (TNM) stage. Prognostic performances of these OS and CSS models were assessed using the Concordance Index (C-index) and area under the curve (AUC) values. Results: The machine learning model had a consistently high accuracy in predicting 6-month, 1-, 2-, 3-, 5-, and 10-year OS in the SEER development set (C-index = 0.861, 0.832, 0.789, 0.766, 0.740, and 0.709; AUC = 0.784, 0.828, 0.840, 0.849, 0.869, and 0.902, respectively), SEER validation set (C-index = 0.782, 0.739, 0.712, 0.698, 0.681, and 0.660; AUC = 0.751, 0.772, 0.767, 0.762, 0.766, and 0.787, respectively), and NCCGC set (C-index = 0.691, 0.756, 0.751, 0.737, 0.722, and 0.701; AUC = 0.769, 0.788, 0.790, 0.790, 0.787, and 0.788, respectively). The model was able to predict 6-month, 1-, 2-, 3-, 5-, and 10-year CSS in the SEER development set (C-index = 0.879, 0.858, 0.820, 0.802, 0.784, and 0.774; AUC = 0.756, 0.827, 0.852, 0.863, 0.874, and 0.884, respectively) and SEER validation set (C-index = 0.790, 0.763, 0.741, 0.729, 0.718, and 0.708; AUC = 0.706, 0.758, 0.767, 0.766, 0.766, and 0.764, respectively). In multivariate analysis, the high-risk group with risk score output by 5-year OS model was proved to be a strong survival predictor both in the SEER development set (hazard ratio [HR] = 14.59, 95% confidence interval [CI]: 1.872–2.774, P < 0.001), SEER validation set (HR = 2.28, 95% CI: 13.089–16.293, P < 0.001), and NCCGC set (HR = 1.98, 95% CI: 1.617–2.437, P < 0.001). We further explored the prognostic value of risk score resulted 5-year CSS model of gastrectomy patients, and found that high-risk group remained as an independent CSS factor in the SEER development set (HR = 12.81, 95% CI: 11.568–14.194, P < 0.001) and SEER validation set (HR = 1.61, 95% CI: 1.338–1.935, P < 0.001). Conclusion: Survival Quilts could allow accurate prediction of 6-month, 1-, 2-, 3-, 5-, and 10-year OS and CSS in gastric cancer patients following gastrectomy.

Abstract Background To discuss the current status of reproductive concerns and its correlation with fear of recurrence and level of family support in patients of childbearing age with gynecologic malignancies. Methods A convenient sampling method was used to enroll 188 patients with gynecologic malignancies in Nanjing Maternity and Child Health Care Hospital, Nanjing Drum Tower Hospital, General Hospital of Ningxia Medical University, and Haian Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from September 2022 to April 2023. Patients were assessed using general information questionnaire, Reproductive Concerns After Cancer Scale (RCAC), Fear of Cancer Recurrence Inventory (FCRI) questionnaire, and Perceived Social Support-Family (PSS-FA) Scale. Results Among patients of childbearing age with gynecologic malignancies, the total RCAC score was (54.35 ± 7.52), indicating a moderate level of reproductive concerns. Patients scored (20.98 ± 4.51) on FCRI, implying a moderate level of fear of recurrence. The PSS-FA score was (9.57 ± 2.76), denoting a moderate level of family support. The total score and each dimensional score of RCAC were positively correlated with FCRI total score (P

Abstract Here a reconfigurable memristor is demonstrated by connecting ZnO film to a fluidic channel. The memristive characteristics are successfully demonstrated with an electrolyte solution. The benefit of using a microfluidic channel is that the memristive characteristics can be adjusted by changing the electrolyte solution in real‐time. The neuromorphic functions such as long‐term plasticity, Spiking‐Rate‐Dependent Plasticity (SRDP), and behavior associated with “learning experiences”are demostrated in the devices. The capability of real‐time manipulating of memristive characteristics enables diverse manipulations on memristive characteristics of the devices, by doping of different concentrated and type of ions in the ZnO film. The electrolyte solution will open new possibilities for resistance switch manipulations, for the next generation neuromorphic computing.

PurposeHaemodynamic management is essential in sepsis management. Invasive blood pressure (IBP) monitoring is the gold standard for blood pressure (BP) assessment. Here, we identified the most advantageous time frame for IBP monitoring to mitigate adverse outcomes in patients with sepsis.MethodsWe included data on patients with sepsis from the Medical Information Mart for Intensive Care IV database. The primary endpoints comprised 28-and 90-day mortality rates, whereas secondary endpoints were acute kidney injury (AKI) rates and continuous renal replacement therapy (CRRT) requirement. To confirm our findings’ robustness, we performed multivariable Cox regression and logistic regression models, augmented by propensity score matching (PSM).ResultsOf 18,326 patients hospitalised for sepsis, 9,056 (49.42%) and 9,270 (50.58%) were included in the early and delayed IBP-monitoring groups, respectively. Our multivariable Cox regression models revealed 20 and 21% significant increases in 28-and 90-day mortality in the delayed IBP monitoring group, respectively [hazard ratios (95% confidence intervals) = 1.20 (1.11–1.31) and 1.21 (1.12–1.31), respectively; both p

Abstract Lymphangiogenesis plays a pivotal role in the pathogenesis of various vascular disorders, including ocular vascular diseases and cancers. Deregulation of N6‐methyladenosine (m6A) modification has been identified as a key contributor to human diseases. However, the specific involvement of m6A modification in lymphatic remodeling remains poorly understood. In this study, we demonstrate that inflammatory stimulation and corneal sutures induce elevated levels of methyltransferase‐like 3 (METTL3)‐mediated m6A modification. METTL3 knockdown inhibits lymphatic endothelial viability, proliferation, migration, and tube formation in vitro. METTL3 knockdown attenuates corneal sutures‐induced lymphangiogenesis and intratumoral lymphangiogenesis initiated by subcutaneous grafts, consequently restraining corneal neovascularization, tumor growth, and tumor neovascularization in vivo. Mechanistically, METTL3 knockdown upregulates prostaglandin–endoperoxide synthase 2 expression through an m6A–YTHDF2‐dependent pathway, enhancing the synthesis of cyclopentenone prostaglandins (CyPGs). Aberrant CyPG production in lymphatic endothelial cells impairs mitochondrial oxidative phosphorylation, contributing to pathological lymphangiogenesis. Moreover, selective inhibition of METTL3 with STM2457 reduces m6A levels in lymphatic endothelial cells, effectively suppressing pathological lymphangiogenesis. This study provides compelling evidence that lymphatic‐specific METTL3 plays a critical role in vascular patterning through prostaglandin metabolism reprogramming. Thus, METTL3 emerges as a promising target for treating lymphangiogenesis‐related diseases.

The rise of technology has heightened work demands, adversely impacting mental health and fitness. The COVID-19 pandemic exacerbates psychological stress, emphasizing the need for non-pharmacological interventions like yoga. Yoga positively influences the autonomic nervous system, benefiting cardio-respiratory health, metabolic efficiency, and conditions like Type-2 diabetes, Chronic Venous disease, and obesity. This study employs a dataset with 100 samples and 43 features related to Chronic Venous Insufficiency (CVI). Logistic and Random Forest classifiers are validated using K-fold cross-validation, with feature selection optimizing prediction accuracy. Hybrid models, enhanced with optimization algorithms, predict Venous Clinical Severity Score (VCSS) before, one, and three months after yoga practices. The Random Forest classifier, particularly RFGT, proves highly accurate in categorizing baseline severity and identifying Mild and Moderate CVI cases. RFGT demonstrated AUC score of 0.9072, 0.8714, 0.7709, and 0.7200 in Absent, Mild, Moderate, and Severe patient groups classification before yoga practices (VCSS-Pre). These values were 0.9158, 0.8644, 0.8142, and 0.6333 for VCSS-1 and reported as 0.9269, 0.8399, 0.7838, and 0.7500 for patients’ classification in VCSS-3. Predicting VCSS scores before yoga intervention assists in categorizing participants for personalized care and efficient resource allocation. The RFC-based models, notably RFGT, show high accuracy in identifying baseline severity, enabling early intervention for high-risk individuals. These models, especially RFGT, perform well in classifying Mild and Moderate CVI cases, informing lifestyle modifications. Predicting VCSS-1 scores evaluates the short-term impact of yoga practices, identifying individuals requiring additional support. RFGT aids in personalized recommendations based on specific factors, crucial for severe conditions. Predicting VCSS-3 scores assesses the sustained impact over three months, identifying intervention responders, particularly in Severe and Moderate groups. RFGT demonstrates optimal predictions, contributing to future interventions tailored to individual responses and improved outcomes.

Abstract Background Current diagnostic criteria of adrenocortical neoplasms are mostly based on morphology. The utility of immunohistochemistry (IHC) and histochemistry is limited. Materials and methods To evaluate the diagnostic and prognostic utility of clinicopathological features, morphology, ancillary biomarkers, and reticular histochemistry in adrenocortical neoplasms. We examined 28 adrenocortical carcinomas (ACCs) and 50 adrenocortical adenomas (ACAs) obtained from pathology archives. Clinical data were retrieved from medical records. Two pathologists independently assessed hematoxylin and eosin-stained slides, employing modified Weiss criteria for all tumors and Lin-Weiss-Bisceglia criteria for oncocytic variants. Immunohistochemical markers (Calretinin, alpha-inhibin, MelanA, SF-1, Ki-67, PHH3, IGF-2, β-catenin, P53, CYP11B1, CYP11B2, MLH1, MSH2, MSH6, PMS2, EPCAM) and Gomori’s Silver histochemistry were applied. Statistical analysis utilized SPSS Statistics 26. Results ACCs exhibited larger tumor sizes (P

Abstract Molecular hydrogen is an emerging broad-spectrum antioxidant molecule that can be used to treat myocardial infarction (MI). However, with hydrogen inhalation, the concentration that can be reached within target organs is low and the duration of action is short, which makes it difficult to achieve high dose targeted delivery of hydrogen to the heart, seriously limiting the therapeutic potential of hydrogen for MI. As a result of reactions with the internal environment of the body, subcutaneous implantation of magnesium slices leads to continuous endogenous hydrogen production, leading to a higher hydrogen concentration and a longer duration of action in target organs. In this study, we propose magnesium implant-based hydrogen therapy for MI. After subcutaneous implantation of magnesium slices in the dorsum of rats, we measured hydrogen production and efficiency, and evaluated the safety of this approach. Compared with hydrogen inhalation, it significantly improved cardiac function in rats with MI. Magnesium implantation also cleared free radicals that were released as a result of mitochondrial dysfunction, as well as suppressing cardiomyocyte apoptosis.

Abstract This paper proposes and investigates a novel 4H‐SiC trench MOSFET (TMOS) with integrated high‐K deep trench and gate dielectric (INHK‐TMOS). The integrated high‐K (INHK) consists of a high‐K gate dielectric and an extended high‐K deep trench dielectric in the drift region. Firstly, the high‐K gate dielectric together with the metal‐forming high‐K metal gate structure, which increases the gate oxide capacitance (COX), reduces the threshold voltage (VTH) and the specific on‐resistance (Ron,sp). Secondly, the extended high‐K deep trench dielectric not only modulates the electric field in the drift region by introducing a new electric field peak at the bottom of the high‐K deep trench dielectric, thereby enhancing the breakdown voltage (BV), but also improves the doping concentration (ND) of the drift region by the assist depletion effect of the high‐K dielectric, further optimizing the forward conduction characteristics. Simulation results demonstrate that when compared to the conventional TMOS, the INHK‐TMOS using HfO2 exhibits a 52.6% reduction in VTH, a 52.1% reduction in Ron,sp, a 20.3% increasement in BV and a 202.3% improvement in figure of merit.

Titanium-magnesium (Ti–Mg) composites have attracted increasing interest recently due to their partial degradability and excellent mechanical properties, which offers a new promise for medical bone implant and repair materials. Here we present a Ti–Mg composite fabricated by pressureless infiltration of pure Mg melt into the 3D-printed pure Ti scaffold. The spatially controllable distribution of phase structure and topology of Mg was achieved by 3D printing technology. The electrochemical corrosion and in vitro degradation behavior of Ti–Mg composite were investigated. The results exhibited that the composite's in vitro degradation rate in 0.9 wt% NaCl solution was faster in the first 48 h due to the influence of galvanic corrosion. After 14 days of immersion, the Mg inside the composite was completely degraded, and the porous Ti maintained its structural integrity throughout the in vitro degradation phase. Additionally, the electrochemical results show that the Ti–Mg composite is more susceptible to corrosion than pure Mg. The overall OCP of the composite tended to increase with increasing immersion time. During the first 24 h of immersion, the impedance value gradually increased due to the thickening of the corrosion product layer. Subsequently, the impedance started to decrease gradually after 3 days of immersion due to the thinning of the Mg(OH)2 film with the continuous degradation of Mg. This study may offer a theoretical reference for the feasibility of partially degradable Ti–Mg composites for long-term bone implants.

Porous asphalt concrete (PAC) is typically used as a paving material for porous asphalt pavement in rainy areas due to its abundant interconnected pores structure. Not all interconnected pores in PAC are valid for permeability, mainly influenced by the composition of aggregate gradation. The main purpose of this paper is to investigate the effect of aggregate gradation on pores structure distribution in PAC by X-ray computed tomography (CT) system and digital image processing (DIP) techniques. The distributions of porosity, number and average equivalent diameter of air voids in middle part are much more evenly compared to the both ends in PAC specimens, accounting for about 70 % of the total of specimen height. The average equivalent diameter of interconnected air voids mainly ranges from 0.5 mm to 5 mm in PAC, accounting for about 80 % of the total numbers. For PAC with similar porosity, the larger the normal maximum aggregate size (NMAS), the less the number and the larger the average equivalent diameter of air voids (interconnected air voids), the smaller the difference between the interconnected porosity and porosity. For PAC with same NMAS, as the porosity increase, the number and average equivalent diameter of air voids (interconnected air voids) are respectively decreased and increased gradually, the difference between the interconnected porosity and porosity is also showed a decreasing trend. And then, the correlated equation is established among porosity, interconnected porosity and the composition of aggregate gradation. The distribution of air voids (interconnected air voids) size could be well described by the two-parameter Weibull model, and the relationships are explored and developed between Weibull model parameters and the composition of aggregate gradation.

Cervical cancer remains a significant health burden in China, characterized by high incidence and mortality rates, which are exacerbated by low Human Papillomavirus (HPV) vaccination coverage, leading to substantial loss of productivity, emotional suffering, and family strain. Understanding factors that influence HPV awareness and knowledge is crucial for developing effective educational strategies. This cross-sectional study, conducted from September to October 2022, involved 2,679 college students from various educational institutions in Jiangsu Province, China. Data were collected via an online questionnaire covering demographics, HPV knowledge, and vaccination behaviors. Statistical analyses, including Chi-square tests and multifactorial logistic regression, were used to identify factors influencing HPV knowledge. The study revealed that while over 90% of students correctly identified HPV’s transmission and risks, significant knowledge gaps and misconceptions persist, particularly regarding HPV’s association with HIV/AIDS and its treatment. Factors significantly associated with better HPV knowledge included age (22–24 years), female gender, being a medical major, being in a relationship, familiarity with HPV, and participation in sexual education programs. Despite a high willingness to receive the HPV vaccine (91.64%), actual vaccination rates remained low. These findings suggest that while Chinese college students were generally aware of HPV, targeted educational interventions are essential to address knowledge gaps and promote HPV vaccination effectively.

ABSTRACTBackground Inflammatory bowel disease (IBD) is characterized by immune-mediated, chronic inflammation of the intestinal tract. The occurrence of IBD is driven by the complex interactions of multiple factors. The objective of this study was to evaluate the therapeutic effects of IAA in colitis.Method C57/BL6 mice were administered 2.5% DSS in drinking water to induce colitis. IAA, Bifidobacterium pseudolongum, and R-equol were administered by oral gavage and fed a regular diet. The Disease Activity Index was used to evaluate disease activity. The degree of colitis was evaluated using histological morphology, RNA, and inflammation marker proteins. CD45+ CD4+ FOXP3+ Treg and CD45+ CD4+ IL17A+ Th17 cells were detected by flow cytometry. Analysis of the gut microbiome in fecal content was performed using 16S rRNA gene sequencing. Gut microbiome metabolites were analyzed using Untargeted Metabolomics.Result In our study, we found IAA alleviates DSS-induced colitis in mice by altering the gut microbiome. The abundance of Bifidobacterium pseudolongum significantly increased in the IAA treatment group. Bifidobacterium pseudolongum ATCC25526 alleviates DSS-induced colitis by increasing the ratio of Foxp3+T cells in colon tissue. R-equol alleviates DSS-induced colitis by increasing Foxp3+T cells, which may be the mechanism by which ATCC25526 alleviates DSS-induced colitis in mice.Conclusion Our study demonstrates that IAA, an indole derivative, alleviates DSS-induced colitis by promoting the production of Equol from Bifidobacterium pseudolongum, which provides new insights into gut homeostasis regulated by indole metabolites other than the classic AHR pathway.

AbstractMultiple endocrine neoplasia type 1 (MEN1), a rare tumor syndrome, is inherited in an autosomal dominant pattern, mainly manifested as primary hyperparathyroidism (PHPT). Surgery is preferred for patients with MEN1 and PHPT. Thermal ablation has been widely applied for PHPT but rarely for postoperative recurrent PHPT in MEN1 patients. Based on a series of cases, we aimed to investigate the clinical efficacy and safety of ultrasound-guided percutaneous microwave ablation in the treatment of MEN1 patients with postoperative recurrence of PHPT.

Linear morphea is the most disabling subtype of morphea, which may cause a series of excutaneous manifestations and sequelae. To futher explore the clinical characteristics of linear morphea, we conducted a retrospective study of 22 patients diagnosed with linear morphea in our department during the past 2 years. Their baseline clinical information, skin manifestations, complications and therapeutic effect were analyzed. Here, we report six cases of a special linear morphea, usually occurring on the unilateral upper limbs of young women, spreading along the distribution of the radial nerve and frequently progressing across the joint, which increases the incidence of neuromusculoskeletal disorders. Instead of traditional topical drugs, a combination of systemic prednisone and methotrexate improved their skin lesions and complications. Recognition of this special type of linear morphea enables earlier diagnosis and active treatment plan, which contributes to ameliorate the symptoms and avoid functional sequelae.

Background: This study aimed to explore the longitudinal associations of rumination with suicidal ideation and suicide attempts in individuals with major depressive disorder (MDD). Methods: Participants were derived from the Depression Cohort in China study (DCC). Those who completed at least one follow-up visit during the 12 months were included in the analysis. Dimensions of rumination including brooding and reflection were each measured using five items of the Ruminative Responses Scale. Suicidal ideation was assessed using the Beck Scale for Suicide Ideation. Suicide attempts were also assessed and all were analyzed with generalized estimating equations. Results: Our final sample included 532 participants aged 18 to 59 years (mean [SD], 26.91 [6.94] years) consisting of 148 (27.8%) males and 384 (72.2%) females. After adjusting for temporal trend and potential confounders, individuals with higher levels of reflection were more likely to report suicidal ideation (AOR =1.11, 95% CI:1.01–1.22). However, no statistically significant association was found between brooding and suicidal ideation (AOR =1.06, 95% CI:0.96–1.17). Conversely, individuals with higher levels of brooding were more likely to report suicide attempts (AOR =1.13, 95% CI:1.02–1.24), while no statistically significant association was observed between reflection and suicide attempts (AOR =0.91, 95% CI:0.82–1.01). Conclusion: Rumination reflects a disturbance in cognitive emotional processing and manifests in different dimensions. Our findings suggest that high levels of reflection and brooding may be associated with a higher likelihood of having suicidal ideation and suicide attempts, respectively. However, it should be interpreted with caution, given that effect sizes are small.

BackgroundBroadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. We conducted a multicenter, randomized, partially blinded Phase I clinical trial to evaluate the safety and serum concentrations of VRC07-523LS, administered in multiple doses and routes to healthy adults without HIV.Methods and findingsParticipants were recruited between 2 February 2018 and 9 October 2018. A total of 124 participants were randomized to receive 5 VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), subcutaneous (SC) (T4: 2.5 mg/kg, T5: 5 mg/kg), or intramuscular (IM) (T6: 2.5 mg/kg or P6: placebo) routes at 4-month intervals. Participants and site staff were blinded to VRC07-523LS versus placebo for the IM group, while all other doses and routes were open-label. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum PK. Neutralization activity was measured in a TZM-bl assay and antidrug antibodies (ADAs) were assayed using a tiered bridging assay testing strategy. Injections and infusions were well tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusion reactions were reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals [95% CIs]) following the first administration were 29.0 μg/mL (25.2, 33.4), 58.5 μg/mL (49.4, 69.3), and 257.2 μg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 μg/mL (8.8, 13.3) and 22.8 μg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 μg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM (95% CIs) concentrations immediately prior to the second administration were 3.4 μg/mL (2.5, 4.6), 6.5 μg/mL (5.6, 7.5), and 27.2 μg/mL (23.9, 31.0) with IV dosing; 0.97 μg/mL (0.65, 1.4) and 3.1 μg/mL (2.2, 4.3) with SC dosing, and 2.6 μg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titers, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A single participant was found to have low titer ADA at a lone time point. VRC07-523LS has an estimated mean half-life of 42 days across all doses and routes (95% CI: 40.5, 43.5), over twice as long as VRC01 (15 days).ConclusionsVRC07-523LS was safe and well tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens.Trial registrationClinicalTrials.gov/ NCT03387150 (posted on 21 December 2017).

We investigate the force sensing of a mechanical membrane in a dissipative cavity optomechanical system (OMS) driven by a squeezed vacuum field accompanying a strong pump laser. Specifically, the red-detuned laser exhibits a more significant improvement for force sensing compared to the blue-detuned laser. The optimal phase angle contributes to achieving much better force sensing. When injecting a squeezed vacuum field with appropriate squeezing parameter and squeezing phase, the standard quantum limit of force measurement can be easily beaten. Furthermore, the adverse effects of the increase in environment temperature and mechanical damping can be suppressed, simultaneously. This scheme provides a theoretical basics for force sensing of mechanical membranes in dissipative OMS and has potential applications in force feedback control, precision measurement, and force sensor design.

Bletilla striata polysaccharide (BSP) is an extract derived from the rare and valuable Chinese herb Bletilla striata [Thunb.] Reichb. f. Although BSP research has progressed considerably, producing portable BSP dressings with hemostatic efficacy remains challenging. This study describes a novel dressing with a reticulate structure. To create this structure, BSP sponges were cross-linked with chitosan and lyophilized. The resulting BSP sponges had excellent mechanical properties, a high density of pores, and an outstanding capacity for fluid absorption. Both in vitro and in vivo experiments demonstrated that the BSP sponges had excellent hemostatic, antibacterial, and anti-inflammatory properties; they also exhibited good stimulation of cell growth and wound healing properties. Furthermore, they were less likely to provoke complications than traditional materials. Cytocompatibility assays revealed that they also stimulated cell proliferation. Therefore, our study suggests that BSP sponges have promising clinical applications as wound dressings.

Carbon peaking and carbon neutralization trigger a technical revolution in energy & environment related fields. Development of new technologies for green energy production and storage, industrial energy saving and efficiency reinforcement, carbon capture, and pollutant gas treatment is in highly imperious demand. The emerging porous framework materials such as metal–organic frameworks (MOFs), covalent organic frameworks (COFs) and hydrogen-bonded organic frameworks (HOFs), owing to the permanent porosity, tremendous specific surface area, designable structure and customizable functionality, have shown great potential in major energy-consuming industrial processes, including sustainable energy gas catalytic conversion, energy-efficient industrial gas separation and storage. Herein, this manuscript presents a systematic review of porous framework materials for global and comprehensive energy & environment related applications, from a macroscopic and application perspective.

An effective SERS-based detection method assisted by machine learning algorithm has been developed to intelligently identify the pharmacodynamic substances in traditional Chinese medicine (TCM) which aided in the quality control and identification of TCM. In this work, the ultrasensitive grating-like core-shell Ag@SiO2@Cu@moth wing (Ag@SiO2@Cu@MW) SERS platform was explored which can precisely control the intergap distances by adjusting the thickness of the SiO2 layer. This SERS platform demonstrated reproducibility and reliability, with a low relative standard deviation (RSD) of 7.38% and an enhancement factor (EF) of 2.49 × 107. The optimized Ag30@SiO2(4)@Cu20@MW substrate were then applied in the accurately analyzing pharmacodynamic substances. Specifically, the label-free SERS analysis showed the distinct spectral features for Jujuboside A, Saikosaponin A and Timosaponin A-III. Machine learning algorithms, such as principal component analysis (PCA), decision tree (DT), support vector machine (SVM), k-nearest neighbors (kNN) were employed and further in differentiating with the three pharmacodynamic substances Raman spectrum groups. These results indicate that SERS technology in combination with machine learning algorithms can not only achieve rapid and accurate detection of different types of pharmacodynamic substances, but also promote the modernization and international application of TCM.

Introduction: For patients with large unresectable hepatocellular carcinoma (HCC), the effectiveness of conventional transarterial chemoembolization (cTACE) remains suboptimal. This study investigated the efficacy and safety of modified TACE using low-dose chemotherapy with blank microspheres (BMS-TACE) plus low-dose lenvatinib (LD-LEN) and microwave ablation (MWA) in patients with large unresectable HCC. Methods: In this prospective, single-arm, phase 2 study, patients with unresectable HCC exceeding the up-to-seven criteria, with maximum tumor diameter ≥7 cm, and without macrovascular invasion or extrahepatic metastases, received initial BMS-TACE (lipiodol, low-dose doxorubicin, and lobaplatin up to 30 mg each, and blank microspheres; subsequently modified and repeated in most patients) plus LD-LEN (4–8 mg/day) and MWA. The primary endpoint was downstaging rate (DSR); secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: From November 2019 to March 2022, 43 patients were enrolled. Median follow-up was 21.2 months. Median largest tumor diameter was 11.2 cm (interquartile range [IQR], 7–25). Following BMS-TACE and LD-LEN, downstaging occurred in 37 (86.0%) patients, 32 of whom received MWA, and 8 of whom had a complete response (CR) without MWA. ORR was 93.0% (CR in 32 [74.4%] and partial response in 8 [18.6%] patients). The 1-, 2-, and 3-year PFS rates were 57.5%, 25.9%, and 18.1%, respectively (median PFS, 14.7 months [95% CI: 8.1–19.5]). The 1-, 2-, and 3-year OS rates were 85.8%, 67.7%, and 61.6%, respectively (median OS, 36.4 months [95% CI: 26.8-not reached]). After BMS-TACE, a significant decline in CD11b+/CD33+/HLA-DR- myeloid-derived suppressor cells and early elevation in CXCR5+/CD8+ and CXCR5+/CD4+ T cells were observed (both p < 0.05). Conclusion: BMS-TACE plus LD-LEN and MWA resulted in promising efficacy and tolerable toxicity in patients with large unresectable HCC exceeding the up-to-seven criteria with a maximum tumor diameter ≥7 cm and without macrovascular invasion or extrahepatic metastases.

This article applied the properties of character sums, quadratic character, and classical Gauss sums to study the calculations of the hybrid power mean of the generalized Gauss sums and the generalized two-term exponential sums. It also provided exact formulas for calculating these hybrid power means.

Abstract Background The HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive. Methods Abatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used. Results In the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045). Conclusion In this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort..

Abstract Amorphous porous organic polymers (aPOPs) are a type of highly crosslinked polymers. These polymers are generally constructed from rigid organic building blocks, which have become an important subclass of POPs with diverse applications. In the early stage of development, a wide range of carbon-based building blocks and network forming chemistry afforded a large library of aPOPs with rich structures and properties. Recently, implanting main group elements with diverse geometric structures and electronic configurations into aPOPs has proven to be a useful tool to fine-tune the structures and properties of these polymers. Herein, we outline the recent advances in the field of main group (MG)-aPOPs where main-group elements either played unique roles in tuning the structures and properties of MG-aPOPs, or offered new strategies in the synthesis of MG-aPOPs. Furthermore, this Review discusses various challenges remaining in the field from the perspectives of synthetic strategies and characterization techniques, and presents some specific studies that may potentially address the challenges.

Abstract Smart city construction is crucial for regional economic development, and the micro-level impact of such construction on business operations cannot be ignored. Based on the panel data of Shanghai and Shenzhen A-share listed companies from 2008 to 2020, this paper investigates the relationship between smart city construction and firm performance and its mechanism of action. The study findings show that (1) smart city construction significantly improves enterprise performance; (2) the improvements are significant across all industries and regions; and (3) the impact of smart city construction on small and medium-sized enterprises (SMEs) and nonstate enterprises is more significant than that on large enterprises and state-owned enterprises. These findings provide a theoretical framework and fresh perspectives for encouraging coordinated regional development and new urbanization construction.

Abstract Background Steatosis and inflammation are the hallmarks of nonalcoholic steatohepatitis (NASH). Rotundic acid (RA) is among the key triterpenes of Ilicis Rotundae Cortex and has exhibited multipronged effects in terms of lowering the lipid content and alleviating inflammation. The study objective is to systematically evaluate the potential mechanisms through which RA affects the development and progression of NASH. Methods Transcriptomic and proteomic analyses of primary hepatocytes isolated from the control, high-fat diet-induced NASH, and RA treatment groups were performed through Gene Ontology analysis and pathway enrichment. Hub genes were identified through network analysis. Integrative analysis revealed key RA-regulated pathways, which were verified by gene and protein expression studies and cell assays. Results Hub genes were identified and enriched in the Toll-like receptor 4 (TLR4)/activator protein-1 (AP1) signaling pathway and glycolysis pathway. RA reversed glycolysis and attenuated the TLR4/AP1 pathway, thereby reducing lipid accumulation and inflammation. Additionally, lactate release in L-02 cells increased with NaAsO2-treated and significantly decreased with RA treatment, thus revealing that RA had a major impact on glycolysis. Conclusions RA is effective in lowering the lipid content and reducing inflammation in mice with NASH by ameliorating glycolysis and TLR4/AP1 pathways, which contributes to the existing knowledge and potentially sheds light on the development of therapeutic interventions for patients with NASH.

AbstractContext Loke zupa decoction (Lok) is a well-established classic Chinese folk remedy for asthma.Objective We sought to investigate the effect and mechanism of Lok on asthma airway remodelling and provide novel insights for the prevention and treatment of asthma.Materials and methods For in vitro experiments, BEAS-2B cells were assigned into six groups: Control, TGF-β1 (10 μM), TGF-β1 + Lok-20, TGF-β1 + Lok-40, TGF-β1 + Lok-80 μg/mL and TGF-β1 + SB431542 (5 μM). CCK8 and wound healing assays were performed. For in vivo experiments, 60 female BALB/c mice were randomly divided into 5 groups: Control, model, Lok-4.55, Lok-9.1, and DEX group. Lok was administrated by gavage during the challenge stage for 8 consecutive weeks (4.55 and 9.1 g/kg/day). We investigated airway inflammation and airway remodelling in the lungs and verified the activation status of EMT-related markers and the PI3K-Akt/HIF-1α signalling pathway.Results In vitro, Lok efficiently inhibited TGF-β1-induced BEAS-2B cell proliferation ability (cell viability 165% vs. 105%) and migration (migration areas 85% vs. 35%) without affecting their normal growth (IC50 274.2 µg/mL at 48 h). In vivo, Lok effectively protected mice from asthma, as evidenced by decreased histological damage and level of cytokines in BALF (IL-4, IL-13 and TGF-β1) by 17%–77%. Mechanistic research revealed that Lok reduced the levels of EMT-related molecules and significantly downregulated the PI3K-Akt/HIF-1α signalling pathway.Discussion and conclusions Our findings provide novel insights into the protective effect of Lok on asthma and the underlying mechanisms, providing a theoretical basis and potential treatment possibilities for this patient population.

The development, differentiation, and function of immune cells are precisely regulated by transcription factors. The E26 transformation-specific (ETS) transcription factor family is involved in various physiological and pathological processes by regulating cell proliferation, differentiation, and apoptosis. Emerging evidence has suggested that ETS family proteins are intimately involved in the development and function of immune cells. This review summarizes the role of the ETS family in immune cells and immune-related disorders. Seven transcription factors within the ETS family, including PU.1, ETV5, ETV6, ETS1/2, ELK3, and ELF1, play essential roles in the development and function of T cells, B cells, macrophages, neutrophils, and dendritic cells. Furthermore, they are involved in the occurrence and development of immune-related diseases, including tumors, allergies, autoimmune diseases, and arteriosclerosis. This review is conducive to a comprehensive overview of the role of the ETS family in immune cells, and thus is informative for the development of novel therapeutic strategies targeting the ETS family for immune-related diseases.

Rapid, universal and accurate identification of chemical composition changes in multi-component traditional Chinese medicine (TCM) decoction is a necessary condition for elucidating the effectiveness and mechanism of pharmacodynamic substances in TCM. In this paper, SERS technology, combined with grating-like SERS substrate and machine learning method, was used to establish an efficient and sensitive method for the detection of TCM decoction. Firstly, the grating-like substrate prepared by magnetron sputtering technology was served as a reliable SERS sensor for the identification of TCM decoction. The enhancement factor (EF) of 4-ATP probe molecules was as high as 1.90 × 107 and the limit of detection (LOD) was as low as 1 × 10−10 M. Then, SERS technology combined with support vector machine (SVM), decision tree (DT), Naive Bayes (NB) and other machine learning algorithms were used to classify and identify the three TCM decoctions, and the classification accuracy rate was as high as 97.78 %. In summary, it is expected that the proposed method combining SERS and machine learning method will have a high development in the practical application of multi-component analytes in TCM.

Mechanism underlying the metabolic benefit of intermittent fasting remains largely unknown. Here, we reported that intermittent fasting promoted interleukin-22 (IL-22) production by type 3 innate lymphoid cells (ILC3s) and subsequent beigeing of subcutaneous white adipose tissue. Adoptive transfer of intestinal ILC3s increased beigeing of white adipose tissue in diet-induced-obese mice. Exogenous IL-22 significantly increased the beigeing of subcutaneous white adipose tissue. Deficiency of IL-22 receptor (IL-22R) attenuated the beigeing induced by intermittent fasting. Single-cell sequencing of sorted intestinal immune cells revealed that intermittent fasting increased aryl hydrocarbon receptor signaling in ILC3s. Analysis of cell-cell ligand receptor interactions indicated that intermittent fasting may stimulate the interaction of ILC3s with dendritic cells and macrophages. These results establish the role of intestinal ILC3s in beigeing of white adipose tissue, suggesting that ILC3/IL-22/IL-22R axis contributes to the metabolic benefit of intermittent fasting.

IntroductionOat (Avena nuda L.) and common vetch (Vicia sativa L.) intercropping in the northern regions of China has resulted in substantial production capabilities. However, there is currently a dearth of comprehensive research on whether this intercropping system can enhance productivity through increased sowing densities and underlying interspecies interaction mechanisms.MethodsA two-year field experiment was conducted in 2022 and 2023 to investigate the yield, biological efficiency, economic efficiency, and competition indicators of oats and common vetch in a high-density intercropping system. Two cropping patterns (monocropping and intercropping) and five sowing densities (D1: 4.5×106 plants ha-1; D2:5.4×106 plants ha-1; D3:6.3×106 plants ha-1; D4: 7.2×106 plants ha-1; and D5: 8.1×106 plants ha-1) were arranged in a randomized block design.ResultsAt the same sowing density, the intercropped oats exhibited greater grain yield than the monocultures. Increasing the oat sowing density significantly enhanced oat yield, with the D3 level in intercropping showing the highest yield increase, ranging from 30.98% to 31.85%, compared with the monoculture. The common vetch intercropping grain yield was maximized in the D2 treatment. The land equivalent ratio was maximized at the D2 level in both years and was significantly higher than D1, with the land equivalent coefficient, system productivity index, and percentage yield difference suggesting that increasing oat sowing densities improved the productivity of the intercropping system, with the best performance observed at the D2 level. For both years, the proportionate actual yield loss of oat was the highest at the D3 level; significantly surpassing D1, proportionate actual yield loss of common vetch and actual yield loss were the highest at level D2, both significantly surpassing D1. These indicates that appropriate densification contributes to the realization of the advantages of intercropping. With an increased oat sowing density, the economic benefits of the intercropping system were maximized at the D2 and D3 levels. Regarding intercropping competition, oat was the dominant crop under different sowing densities (Aggressivity for oat (AO)>0, relative crowding coefficient for oat (KO)>1, competition ratio for oat (CRO)>1), whereas common vetch was the inferior crop. Compared with the D1 level, the D2 level harmonized the aggressivity, competitive ratio, and relative crowding coefficients of oat and common vetch, significantly increasing crowding coefficient for common vetch (KV) and competition ratio for common vetch by 19.76% to 21.94% and 4.80% to 7.51%, respectively, while reducing KO and CRO.DiscussionThis result suggests that in the intercropping of common vetch and oat in alpine regions, rational densification can harmonize interspecific competition and thus improve the biological efficiency and economic benefits of intercropping systems.

Abstract Background Long non-coding RNAs (lncRNAs) are critical regulators in the initiation and progression of breast cancer. Our study aims to characterize the functions of LINC02086 which few published in breast cancer and decipher the downstream molecular mechanisms. Methods LINC02086 expression is tested in RNA-seq data from GEPIA database, tumor tissue samples from hospital patients and breast cancer cell lines. LINC02086 was silenced or overexpressed by lenti-virus-mediated shRNAs, or pLVX-Puro plasmids. Luciferase reporter assay and RNA pull-down assay were applied to study interactions between LINC02086, miR-6757-5p and ephrin type-A receptor 2 (EPHA2). LINC02086-silencing MCF-7 cells were injected into mice to establish xenograft animal models. Results Using RNA-seq data, tumor tissue samples and breast cancer cells, LINC02086 was consistently found to be up-regulated in breast cancer, and correlated with poorer prognosis. LINC02086 knockdown decreased cell viability, promoted cell apoptosis and suppressed tumor growth. LINC02086 interacted with miR-6757-5p that interacted with EPHA2.LINC02086 expression was negatively correlated with miR-6757-5p expression (r = -0.5698, P

Background Research has shown that a fundamental frequency of 40 Hz in continuous neural oscillation is indicative of normal brain activity; in Alzheimer disease (AD) patients, these oscillations either disappear or are significantly interrupted. Research has also indicated that the degenerative impacts of AD in mice were mitigated by the synchronization of 40-Hz acousto-optic stimulation (AOS).

Abstract Objective This study aimed to explore the efficacy and safety of combining epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with ZiLongJin Tablet (ZLJT) in delaying acquired resistance in advanced EGFR-mutant lung adenocarcinoma (LUAD) patients. Furthermore, we employed network pharmacology and molecular docking techniques to investigate the underlying mechanisms. Methods A retrospective comparative study was conducted on stage IIIc/IV LUAD patients treated with EGFR-TKIs alone or in combination with ZLJT at the Second Affiliated Hospital of the Air Force Medical University between January 1, 2017, and May 1, 2023. The study evaluated the onset of TKI resistance, adverse reaction rates, safety indicators (such as aspartate aminotransferase, alanine aminotransferase, and creatinine), and inflammatory markers (neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio) to investigate the impact of EGFR-TKI combined with ZLJT on acquired resistance and prognostic indicators. Additionally, we utilized the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine, PubChem, UniProt, and Swiss Target Prediction databases to identify the active ingredients and targets of ZLJT. We obtained differentially expressed genes related to EGFR-TKI sensitivity and resistance from the Gene Expression Omnibus database using the GSE34228 dataset, which included sensitive (n = 26) and resistant (n = 26) PC9 cell lines. The "limma" package in R software was employed to detect DEGs. Based on this, we constructed a protein‒protein interaction network, performed gene ontology and KEGG enrichment analyses, and conducted pathway network analysis to elucidate the correlation between the active ingredients in ZLJT and signaling pathways. Finally, molecular docking was performed using AutoDockVina, PYMOL 2.2.0, and Discovery Studio Client v19.1.0 software to simulate spatial and energy matching during the recognition process between predicted targets and their corresponding compounds. Results (1) A total of 89 patients were included, with 40 patients in the EGFR-TKI combined with ZLJT group (combination group) and 49 patients in the EGFR-TKI alone group (monotherapy group). The baseline characteristics of the two groups were comparable. There was a significant difference in the onset of resistance between the combination group and the monotherapy group (P 0.05). There were no statistically significant differences in serum AST, ALT, CREA, TBIL, ALB and BUN levels between the two groups after medication (P > 0.05). (3) Regarding inflammatory markers, there were no statistically significant differences in the changes in neutrophil-to-lymphocyte Ratio(NLR) and Platelet-to-lymphocyte Ratio(PLR) values before and after treatment between the two groups (P > 0.05). (4) Network pharmacology analysis identified 112 active ingredients and 290 target genes for ZLJT. From the GEO database, 2035 differentially expressed genes related to resistant LUAD were selected, and 39 target genes were obtained by taking the intersection. A "ZLJT-compound-target-disease" network was successfully constructed using Cytoscape 3.7.0. GO enrichment analysis revealed that ZLJT mainly affected biological processes such as adenylate cyclase-modulating G protein-coupled receptor. In terms of cellular components, ZLJT was associated with the cell projection membrane. The molecular function primarily focused on protein heterodimerization activity. KEGG enrichment analysis indicated that ZLJT exerted its antitumor and anti-drug resistance effects through pathways such as the PI3K-Akt pathway. Molecular docking showed that luteolin had good binding activity with FOS (-9.8 kJ/mol), as did tanshinone IIA with FOS (-9.8 kJ/mol) and quercetin with FOS (-8.7 kJ/mol). Conclusion ZLJT has potential antitumor progression effects. For patients with EGFR gene-mutated non-small cell LUAD, combining ZLJT with EGFR-TKI treatment can delay the occurrence of acquired resistance. The underlying mechanisms may involve altering signal transduction pathways, blocking the tumor cell cycle, inhibiting tumor activity, enhancing cellular vitality, and improving the bioavailability of combination therapy. The combination of EGFR-TKI and ZLJT represents an effective approach for the treatment of tumors using both Chinese and Western medicine.

Abstract Background Response of locally advanced gastric cancer (LAGC) to neoadjuvant therapy (NAT) may be associated with prognosis, but which of the clinical or pathological evaluation can accurately predict a favorable prognosis is still controversial. This study aims to compare the effect of clinical and pathological response on the prognosis of patients with gastric cancer. Methods This study retrospectively analyzed LAGC patients who underwent NAT followed by surgery in the China National Cancer Center from January 2004 to January 2021. Clinical and pathological responses after NAT were evaluated using RECIST 1.1 and Mandard tumor regression grade system (TRG) respectively. Complete response (CR) and partial response (PR) assessed by computed tomography were regarded as clinical response. For histopathology regression assessment, response was defined as Mandard 1, 2, 3 and non-response as Mandard 4, 5. Furthermore, we combined clinical and pathological evaluation results into a variable termed “comprehensive assessment” and divided it into four groups based on the presence or absence of response (concurrent response, only clinical response, only pathological response, both non-response). The association between the prognosis and clinicopathological factors was assessed in univariate and multivariate Cox regression analysis. Results In total, 238 of 1073 patients were included in the study after screening. The postoperative pathological response rate and clinical response rate were 50.84% (121/238) and 39.92% (95/238), respectively. 154 patients got consistent results in clinical and pathological evaluation (66 were concurrent response and 88 were both non-response), while the other 84 patients did not. The kappa value was 0.297(p

Abstract Vessel Traffic Service (VTS) significantly improves the navigation efficiency of ports. This paper proposes a model called Joint Extraction of Triples from the VHF Speech (JER‐VHF) to ensure the efficiency of the VTS. Numerous texts are extracted from the Very High Frequency (VHF) speech communication contents and these texts are organized into a dataset named VHFDT. The proposed model's transforming task transforms the voice communication contents of this dataset into a triple representation. VHFDT has a large number of overlapping triples. Therefore, this paper proposes a combined model with three categories to model the entity relations in VHF sentences, including pre‐training Chinese language model for initializing embedding from VHFDT, BiLSTM for rich features, and Multi‐head Attention for focusing on triples. In experimental part, this study uses Precision(P), Recall(R), and F1 to evaluate the accuracy and effectiveness of the proposed method and baseline models. According to experimental results, the proposed model efficiently extracts the key information from complex language environment and achieves better work on relational triple extraction than other baseline models. The model achieved an F1‐score of 83.2% on the overlapping testing data, which is an improvement of 1.8% compared to the second‐best baseline model.

Abstract Background Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease which results in inherited bone marrow failure (IBMF) and is characterized by exocrine pancreatic dysfunction and diverse clinical phenotypes. In the present study, we reviewed the internationally published reports on SDS patients, in order to summarize the clinical features, epidemiology, and treatment of SDS. Methods We searched the WangFang and China National Knowledge Infrastructure databases with the keywords “Shwachman-Diamond syndrome,” “SDS,” “SBDS gene” and “inherited bone marrow failure” for relevant articles published from January 2002 to October 2022. In addition, studies published from January 2002 to October 2022 were searched from the Web of Science, PubMed, and MEDLINE databases, using “Shwachman-diamond syndrome” as the keyword. Finally, one child with SDS treated in Tongji Hospital was also included. Results The clinical features of 156 patients with SDS were summarized. The three major clinical features of SDS were found to be peripheral blood cytopenia (96.8%), exocrine pancreatic dysfunction (83.3%), and failure to thrive (83.3%). The detection rate of SDS mutations was 94.6% (125/132). Mutations in SBDS, DNAJC21, SRP54, ELF6, and ELF1 have been reported. The male-to-female ratio was approximately 1.3/1. The median age of onset was 0.16 years, but the diagnostic age lagged by a median age of 1.3 years. Conclusions Pancreatic exocrine insufficiency and growth failure were common initial symptoms. SDS onset occurred early in childhood, and individual differences were obvious. Comprehensive collection and analysis of case-related data can help clinicians understand the clinical characteristics of SDS, which may improve early diagnosis and promote effective clinical intervention.