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Abstract This web-based cross-sectional study aimed to evaluate the knowledge, attitudes, and practices of physicians and hospital pharmacists towards polypharmacy in older adult patients with chronic diseases in China. This study enrolled 374 physicians and pharmacists (270 females, 92 physicians) in 20 Chinese provinces between December 2022 and March 2023. The knowledge, attitude, and practice scores were 12.65 ± 2.05 (possible range, 0–18), 29.07 ± 2.68 (possible range, 7–35), and 26.16 ± 5.56 (possible range, 7–35), respectively. Working as a hospital pharmacist (vs. physician) was independently associated with adequate knowledge (OR = 2.190; 95% CI = 1.291–2.713; P = 0.004). Working in a tertiary hospital (OR = 4.296; 95% CI = 1.390-13.272; P = 0.011) was independently associated with a positive attitude. Knowledge score (OR = 1.176; 95%CI = 1.038–1.333; P = 0.011), hospital pharmacist (OR = 0.276; 95% CI = 0.137–0.557; P

In recent years, the escalating impact of climate change has brought increasing attention to carbon-neutral strategies as a critical component of global environmental protection efforts. These strategies demand a comprehensive understanding of carbon emissions, which are influenced by a myriad of factors, including external conditions like seasonality and weather, as well as internal dynamics such as production and energy consumption. However, existing approaches often fail to account for these complex, dynamic interactions, resulting in suboptimal outcomes. To address these challenges, we propose an integrated model combining Autoformer, Deep Q-Network (DQN), and Deep Forest. This model is designed to dynamically respond to environmental changes using advanced time-series forecasting, adaptive decision-making, and robust feature extraction. Extensive experiments across multiple datasets reveal that our model significantly enhances carbon capture efficiency and accuracy, outperforming conventional methods. By providing a scalable and intelligent solution for carbon capture and utilization, this research not only supports the advancement of carbon-neutral strategies but also contributes to the broader goals of sustainable development and climate change mitigation.

Adenoid cystic carcinoma (ACC) is a rare malignancy predominantly found in the salivary, lacrimal, upper gastrointestinal, and respiratory mucosal glands; adenoid cystic carcinoma of the external auditory canal (EAC) is particularly rare. Characterized by a proclivity for recurrence and metastasis, advanced adenoid cystic carcinoma often proves refractory to conventional chemotherapy. Novel therapeutic approaches, notably targeted therapies, are imperative to enhance treatment response rates in advanced adenoid cystic carcinoma patients. Herein, we present a case of primary adenoid cystic carcinoma affecting the right external auditory canal in a 56-year-old male presenting with symptoms of pruritus, swelling, pain, and hearing loss in the affected ear. Despite multiple attempts with diverse chemotherapy regimens yielding no success, the patient developed advanced lung metastases, prompting the utilization of anlotinib-targeted therapy. Subsequent administration of anlotinib led to a partial remission (PR), resulting in approximately 8 months of progression-free survival (PFS) in this individual.

[Objective] Climate warming has a significant impact on crop cultivation pattern. The purpose of this paper is to explore the relationship between climate warming and crop cultivation pattern, and to clarify the degree of contribution of different influencing factors to crop growth, so as to provide reference for regional cultivation structure adjustment and layout optimization. [Methods] Based on the 2000, 2010, and 2020 crop classification data, this study analyzed the trend of changes in maize and soybean cultivation scale and pattern under climate warming using the GIS grids and geo-information maps. The maximum entropy model was employed to reveal the main factors driving the change in the spatiotemporal crop planting patterns. [Results] (1) In terms of scale, the change in the planting area indicated an increase in maize planting area; conversely, the soybean planting area decreased. Heilongjiang Province, the largest increase in maize planting area of 69.01%, Jilin Province, the largest decrease in soybean planting area of 68.21%. (2) The transitional zone for maize and soybean cultivation in the Northeast region shifted noticeably northward between 2000 and 2020. Among them, the transition zone for maize and soybean cultivation moved northward by about 129.10 km in Songnen Plain from 2000 to 2010, and moved northward by about 283.80 km in Sanjiang Plain from 2010 to 2020. (3) The dominant bioclimatic factors influencing changes in the suitability of maize planting and the movement of planting areas in the Northeast were the average temperature of the hottest season and the average temperature of the driest season, respectively. The northern boundary of the maize and soybean planting transitional zone is mainly located within the ≥10 ℃ active cumulative temperature range of 2900-3100 ℃, and as this cumulative temperature zone continues to move northward, the planting transitional zone moves along with it. [Conclusion] The planting structure and layout of maize and soybean in Northeast China from 2000 to 2020 were significantly changed by temperature. In the future, more attention needs to be paid to the impact of climate change on crop cultivation in order to promote the sustained and healthy development of agricultural production and ensure the long-term stability of food security.

Making time-series forecasting in a robust way is a difficult task only based on the observed data of a nonlinear system. In this work, a neural network computing framework, the spatiotemporal information conversion machine (STICM), was developed to efficiently and accurately render a forecasting of a time series by employing a spatial-temporal information (STI) transformation. STICM combines the advantages of both the STI equation and the temporal convolutional network, which maps the high-dimensional/spatial data to the future temporal values of a target variable, thus naturally providing the forecasting of the target variable. From the observed variables, the STICM also infers the causal factors of the target variable in the sense of Granger causality, which are in turn selected as effective spatial information to improve the robustness of time-series forecasting. The STICM was successfully applied to both benchmark systems and real-world datasets, all of which show superior and robust performance in time-series forecasting, even when the data were perturbed by noise. From both theoretical and computational viewpoints, the STICM has great potential in practical applications in artificial intelligence or as a model-free method based only on the observed data, and also opens a new way to explore the observed high-dimensional data in a dynamical manner for machine learning.

Abstract Purpose To evaluate the availability of human resources for ophthalmic services in mainland China. Methods In 2021, we conducted a nationwide survey of ophthalmic outpatient services across 2996 tertiary hospitals and 10,404 secondary hospitals in 31 provinces in mainland China. Results The response rate was 73.6% (9856/13400), with 78.7% (7759/9856) providing ophthalmic services. By 2021, the total number of ophthalmologists, ophthalmic nurses, and optometrists was 48,652, 64,495, and 14,320, respectively. The densities (per 50,000 population) were 1.7, 2.25, and 0.47, respectively. The density of ophthalmologists was

Abstract Background Effective screening for colorectal cancer (CRC) enables earlier diagnosis and intervention to improve patient survival. Methods In this study, we prospectively conducted a blood-based CRC screening program for community residents in Hanjiang District, Yangzhou City, and evaluated the screening efficacy of a blood-based multi-locus DNA methylation assay (ColonAiQ). The ColonAiQ-positive rate and colonoscopy participation rate of the population, detection rate of intestinal lesions, and positive predictive value (PPV) of CRC and advanced adenoma (AA) were calculated, and the associated factors were explored. Results A total of 105,285 participants were enrolled from January 2021 to December 2022, all of whom completed the ColonAiQ assay, yielding a positive rate of 6.42% (6759/105,285). The colonoscopy compliance rate was 48.56% (3282/6759). Intestinal lesions were detected in 1773 individuals (54.02%), including 63 cases of CRCs (predominately early-stage), 1195 adenomas (441 cases of AAs), 327 polyps, and 188 other benign lesions. CRC patients exhibited higher ColonAiQ scores and more positive loci compared to healthy individuals. The PPVs were 1.92% for CRC and 13.44% for AA. Among participants, 66,121 (62.8%) completed questionnaires graded by the Asia–Pacific Colorectal Screening score, with 12,139 (18.36%) classified in the high-risk tier. High-risk participants had a higher ColonAiQ-positive rate (11.07%) and PPVs for CRC (3.46%) and AA (22.18%). Factors associated with increased detection rates for CRC and AA included male gender, older age, a history of alcohol consumption, and prior polyps. Conclusions Our study demonstrated that ColonAiQ assay effectively identifies high-risk population. These findings strongly suggest that the ColonAiQ assay represents a promising strategy for the early detection of CRC and AA in individuals at average risk. Trial registration Registered at ClinicalTrials.gov (NCT05336539).

Abstract Background B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T-cell (CAR T-cell) therapy has exhibited remarkable efficacy in refractory or relapsed multiple myeloma (R/R MM), but recurrence and rapid progression of disease are still observed within a short time after treatment. Long-term pomalidomide therapy, which potentiates T-cell functionality, might enhance the efficacy of BCMA CAR T-cell therapy. Methods We performed a single-center retrospective clinical study. Patients with relapsed or refractory multiple myeloma who received BCMA CAR T-cell infusion were enrolled in our study, and were followed by long-term pomalidomide treatment (4 mg/day) or not one month after infusion. The response and adverse events were assessed after infusion. The effect of pomalidomide on BCMA CAR T-cells was assessed in vitro. Results The objective response rate (ORR) of BCMA-CART was 100%. Three months following CAR T-cell infusion, of the 8 patients receiving pomalidomide, except for 2 patients who stopped maintenance therapy and were lost to follow-up, all patients (6/6) achieved VGPR (very good partial response) or CR (complete response), while only 5 patients (5/8) who did not receive pomalidomide treatment achieved VGPR or better. At a median follow-up of 27 months, for the 8 patients who did not receive pomalidomide administration, the median TTP (time to progression) was 5.85 (1–14) months, while the OS (overall survival) was 10.7 (1.2–16) months. Of the 8 patients who received pomalidomide therapy after CAR T-cell infusion, the median TTP was 13 (7–13) months, while the OS was not reached. Moreover, neither long-term hematological toxicity nor drug-induced liver damage was observed during the follow-up period. Mechanistically, pomalidomide promotes antimyeloma efficacy of BCMA CAR T-cells by inhibiting cell apoptosis and enhancing cytoxicity. Conclusions Our results confirmed that BCMA CAR T-cell therapy combined with long-term pomalidomide had a low recurrence rate and manageable therapy-related side effects, providing a promising option for treating R/R MM. Graphical Abstract

Liquid droplet impingement (LDI) treatment changes the roughness and introduces residual compressive stress on 321 stainless steel (SS). Compared to untreated 321 SS, 1 h of LDI treatment with 100, 150 and 175 m/s gradually increases the pitting potential of 321 SS, while 1 h of LDI treatment with 200 m/s decreased the pitting potential of 321 SS. The passive films grown on the 321 SS after LDI treatment with 100, 150 and 175 m/s show a decreased receptor density, an increased Cr content and an increased thickness, whereas a dense passive film with good corrosion resistance cannot be formed on the 321 SS after LDI treatment with 200 m/s. The effect of the change in surface state due to LDI treatment on the electrochemical passivation behavior is explained in detail.

Study Design Retrospective clinical study. Objective The purpose of this study was to establish a novel classification of migrated lumbar disk herniation (LDH) based on magnetic resonance imaging and provide appropriate treatment strategies for each type through algorithms. Summary of Background Data Full‐endoscopic lumbar discectomy is a surgical technique that has been developed rapidly in recent years. For migrated LDH, few surgeons currently classify it with multiplanar positioning, and there is no consensus on the choice of treatment strategy. Therefore, we established a new multiplanar classification criteria that can localize the lesions more accurately than previous studies. Methods A total of 263 eligible patients from March 2017 to March 2022 were included. Protrusions for each patient were located based on our classification and the surgical approach was selected according to our algorithms. The clinical symptoms of all patients before surgery, and at 1 day, 1 month, 3 months, 6 months, and 12 months after surgery were collected. Evaluations were performed using visual analogue scale (VAS), Oswestry Disability Index (ODI) and modified MacNab criteria. We used the chi‐squared test, one‐way analysis of variance (ANOVA), and t‐test to compare perioperative results and postoperative 3‐month, 6‐month, and 12‐month follow‐up results. Results VAS (low back pain) scores were reduced from 5.33 ± 2.67 to 0.73 ± 0.77 (p

Abstract Obstructed atomic insulator is recently proposed as an unconventional material, in which electric charge centers localized at sites away from the atoms. A half-filling surface state would emerge at specific interfaces cutting through these charge centers and avoid intersecting any atoms. In this article, we utilized photoemission spectroscopy and density functional theory calculations to study one of the obstructed atomic insulator candidates, NiP2. A floating surface state with large effective mass that is close to the Fermi level and isolated from all bulk states is resolved on the (100) cleavage plane, implying better catalytic activity in this plane than the previously studied surfaces. Density functional theory calculation results elucidate that this floating surface state is originated from the obstructed Wannier charge centers, albeit underwent surface reconstruction. Our findings not only shed lights on the study of obstructed atomic insulators, but also provide possible route for development of new catalysts.

Molecular dynamics simulations were carried out to investigate the tensile deformation behavior of Ni50Co50 solid solution nanocrystalline alloys with varying degrees of grain boundary segregation. A comprehensive analysis disclosed that the observed strengthening in the Ni-rich grain boundary model is primarily due to the formation of Lomer-Cottrell locks and dislocation networks which impede dislocation motion. Plastic deformation, on the other hand, is predominantly governed by enhanced grain boundary migration, grain rotation, and deformation twinning. In the Co-rich grain boundary model, the interactions among twins, dislocations, and grain boundaries, stemming from the formation of extensive stacking faults and twinning, dictate the plastic deformation and strengthening. Fluctuations in grain boundary composition promote stress concentration, thereby facilitating plastic deformation and dislocation accumulation within the grain, which in turn enhances strain hardening. The study reveals that the Ni50Co50 solid solution nanocrystalline alloys exhibit both high tensile strength and favorable plasticity for models with grain boundary segregation around ±10%. These insights provide valuable guidance for the development of Ni50Co50 nanocrystalline alloys with optimized strength and toughness.

Breast cancer represents one of the most prevalent malignant neoplasms affecting women, and its pathogenesis has garnered significant scholarly interest. Research indicates that the progression of breast cancer is intricately regulated by glucose metabolism. Under hypoxic conditions within the tumor microenvironment, breast cancer cells generate ATP and essential biosynthetic precursors for growth via the glycolytic pathway. Notably, phosphoglycerate kinase 1 (PGK1) is intimately associated with the regulation of hypoxia-inducible factors in breast cancer and plays a crucial role in modulating glycolytic processes. Further investigation into the role of PGK1 in breast cancer pathogenesis is anticipated to identify novel therapeutic targets and strategies. This review consolidates current research on the regulation of glucose metabolism and the function of PGK1 in breast cancer within hypoxic conditions. It aims to offer a significant theoretical foundation for elucidating the mechanisms underlying breast cancer progression and metastasis, thereby facilitating the development of innovative treatment approaches.

Polymer-derived ceramic (PDC)-SiOC is a highly promising microwave-absorbing material characterized by high temperature resistance, lightweight, high strength, and extremely low cost. The weak electromagnetic wave (EMW) attenuation capacity and poor flexibility of single precursor-derived SiOC ceramics significantly limit their further application. This study employs a simple electrospinning technique to uniformly distribute Co and TiO2 within amorphous SiOC nanofibers. The three-dimensional porous structure formed by continuous nanofibers endows Co/TiO2/SiOCs with high porosity, significantly reducing the thermal conductivity and enhancing the conductive loss of electromagnetic waves within the nanofiber mats. Additionally, the introduction of Co and Ti promotes nanostructuring of the fibers and introduces polarization interfaces and defects, thereby enhancing the polarization loss of the samples. With a filler content of only 5 wt%, the Co/TiO2/SiOC sample heat-treated at 800 °C (in silicone resin) exhibits an effective absorption bandwidth (EAB) of up to 8.64 GHz (9.36–18.00 GHz) at a thickness of 3.25 mm, achieving a minimum reflection loss (RLmin) value of −66.00 dB at 17.11 GHz with a matching thickness of 2.50 mm. Moreover, the nanofiber mats also demonstrate excellent thermal insulation performance (thermal conductivity ranging < 0.041 W·m−1·k−1), remarkable flexibility (the resistance change rate after 1500 cycles of 180° bending test is less than 4%), and impressive resilience performance (residual strain < 12% after 500 cycles under 60% strain conditions). The successful preparation of such multi-functional nanofiber mats is promising for the application of thermal and microwave protection.

Abstract Background Postoperative pain (PP) is a dynamic process that reflects the complex interplay between symptoms, treatment, and patient experiences, and its intensity is reportedly primarily related to the severity of surgical trauma. However, no large-scale national database-based study has hitherto been conducted to assess the occurrence and features related to PP following breast cancer (BC) surgery. Methods In this retrospective analysis, we screened BC surgery cases between 2015 and 2019 within the National Inpatient Sample (NIS) Database, utilizing the International Classification of Diseases (ICD) 10th edition clinical modification codes. The researchers identified patients who developed PP and compared them to those who did not. Factors associated with PP were then screened: patient demographics (age and race), hospital characteristics (type of insurance, bed size, teaching status, type of admission, location, and hospital area), length of stay (LOS), total cost during hospitalization, inpatient mortality, comorbidities, and perioperative complications. Data were analyzed using descriptive statistics. Multivariate logistic regression analysis was used to determine the independent risk factors for postoperative pain in BC surgery. Results 39,870 BC surgery cases were identified over a five-year period from 2015 to 2019. The overall occurrence of PP following breast cancer surgery was 6.15% (2,387 cases), with a slight upward trend every year. Significant racial disparities were observed, Whites associated with a higher incidence of PP (P

Abstract Background Accurate differentiation between malignant and benign pulmonary nodules, especially those measuring 5–10 mm in diameter, continues to pose a significant diagnostic challenge. This study introduces a novel, precise approach by integrating circulating cell-free DNA (cfDNA) methylation patterns, protein profiling, and computed tomography (CT) imaging features to enhance the classification of pulmonary nodules. Methods Blood samples were collected from 419 participants diagnosed with pulmonary nodules ranging from 5 to 30 mm in size, before any disease-altering procedures such as treatment or surgical intervention. High-throughput bisulfite sequencing was used to conduct DNA methylation profiling, while protein profiling was performed utilizing the Olink proximity extension assay. The dataset was divided into a training set and an independent test set. The training set included 162 matched cases of benign and malignant nodules, balanced for sex and age. In contrast, the test set consisted of 46 benign and 49 malignant nodules. By effectively integrating both molecular (DNA methylation and protein profiling) and CT imaging parameters, a sophisticated deep learning-based classifier was developed to accurately distinguish between benign and malignant pulmonary nodules. Results Our results demonstrate that the integrated model is both accurate and robust in distinguishing between benign and malignant pulmonary nodules. It achieved an AUC score 0.925 (sensitivity = 83.7%, specificity = 82.6%) in classifying test set. The performance of the integrated model was significantly higher than that of individual methylation (AUC = 0.799, P = 0.004), protein (AUC = 0.846, P = 0.009), and imaging models (AUC = 0.866, P = 0.01). Importantly, the integrated model achieved a higher AUC of 0.951 (sensitivity = 83.9%, specificity = 89.7%) in 5–10 mm small nodules. These results collectively confirm the accuracy and robustness of our model in detecting malignant nodules from benign ones. Conclusions Our study presents a promising noninvasive approach to distinguish the malignancy of pulmonary nodules using multiple molecular and imaging features, which has the potential to assist in clinical decision-making. Trial registration: This study was registered on ClinicalTrials.gov on 01/01/2020 (NCT05432128). https://classic.clinicaltrials.gov/ct2/show/NCT05432128 .

Abstract The purpose of this study is to investigate the influencing factors of abnormal pulmonary ventilation function in occupational exposed populations and to establish a risk prediction model. The findings will provide a basis for formulating corresponding strategies for the prevention and treatment of occupational diseases. The study focused on workers who underwent occupational health examinations in the year 2020. Statistical analysis was conducted using methods such as t-tests, chi-square tests, and multiple logistic regression analysis. Additionally, machine learning methods were employed to establish multiple models to address classification problems. Among the 7472 workers who participated in the occupational health examination, 1681 cases of abnormal pulmonary ventilation function were detected, resulting in a detection rate of 22.6%. Based on the analysis of occupational hazard data, a risk prediction model was established. Age, work tenure, type of the employing enterprise, and type of dust exposure are all identified as driving factors for abnormal pulmonary function. These factors were used as predictive variables for establishing the risk prediction model. Among the various models evaluated, the logistic regression model was found to be the optimal model for predicting abnormal pulmonary ventilation function.

Tubular microfibers have recently attracted extensive interest for applications in tissue engineering. However, the fabrication of tubular fibers with intricate hierarchical structures remains a major challenge. Here, we present a novel one-step microfluidic spinning method to generate bio-inspired screwed conduits (BSCs). Based on the microfluidic rope-coiling effect, a viscous hydrogel precursor is first curved into a helix stream in the channel, and then consecutively packed as a hollow structured stream and gelated into a screwed conduit (SC) via ionic and covalent crosslinking. By taking advantage of the excellent fluid-controlling ability of microfluidics, various tubes with diverse structures are fabricated via simple control over fluid velocities and multiple microfluidic device designs. The perfusability and permeability results, as well as the encapsulation and culture of human umbilical vein endothelial cells (HUVECs), human pulmonary alveolar epithelial cells (HPAs), and myogenic cells (C2C12), demonstrate that these SCs have good perfusability and permeability and the ability to induce the formation of functional biostructures. These features support the uniqueness and potential applications of these BSCs as biomimetic blood vessels and bronchiole tissues in combination with tissue microstructures, with likely application possibilities in biomedical engineering.

Abstract Background Increased intracranial pressure (ICP) in patients with idiopathic intracranial hypertension (IIH) affects the retinal microvasculature, which can be imaged and quantified by optical coherence tomography angiography (OCTA). We aimed to identify the mediating factor between ICP and OCTA parameters association in IIH patients. Methods IIH patients with active intracranial hypertension were enrolled. OCTA imaging was performed after ICP measurement. We quantified the branching complexity of the retinal arterioles and venules from the superficial vascular complex of the OCTA image. Eyes of IIH patients were stratified into eyes with papilledema (IIH-P) and eyes without papilledema (IIH-WP). All participants underwent visual acuity (VA) examination. Results One hundred and thirty-eight eyes from 70 IIH patients and 146 eyes from 73 controls were included. Compared to the control group, IIH patients and IIH-P had reduced arteriole complexity and increased venule complexity (p

To screen and identify high chitosanase producing strains and to optimize the fermentation condition and analyze the enzymatic properties of the target strain. In this study, high chitosanase-producing strain was screened from the sediment of shrimp ponds in Beihai, Guangxi through primary and secondary screening. The strain underwent identification, the enzyme production process of the strain was optimized through single-factor, Plackett-Burman and orthogonal optimization methods. The enzymatic properties and products of chitosanase produced by the strain were studied. The results showed that the strain of Gxun-5.3.3 with high chitosanase production was obtained by screening and was identified as Bacillus cereus. The optimal components for the enzyme-producing medium of B. cereus Gxun-5.3.3 was maltose 5 g/L, yeast powder 3 g/L, chitosan 15 g/L, and the initial pH and fermentation time were 6.0 and 84 h, respectively. Under the optimized conditions, the chitosanase activity reached 62.03±1.18 U/mL, which was 55.58% higher before optimization (39.87±1.24 U/mL). The protease produced by strain Gxun-5.3.3 had maximum activity at 60 ℃ and optimum pH at 5.0, respectively. Metal ions Fe2+ and Mn2+ had a significant (P

Abstract Background Spinal cord injury (SCI) results in severe, permanent functional changes and has become a global health priority due to its high incidence, cost, and disability rate. Current national epidemiological data on SCI in China are limited and outdated. This study aimed to provide a comprehensive, national cross-sectional investigation of SCI epidemiology in China. Methods This cross-sectional study included 3055 SCI participants aged 8 to 78 years, conducted from May to September 2023. Data collected encompassed demographic characteristics, employment status, etiology, years lived with disability (YLD), family structure, caregiving status, income, health insurance, paralysis type, and health-related quality of life (HRQoL). Descriptive statistics analyses were used to assess demographic and injury characteristics. Group differences were assessed using t-tests, one-way ANOVA and Chi-square tests. Significant factors were examined using multivariate regression analysis. Results The majority (88.9%) of respondents were aged 15 to 59 years, with a male-to-female ratio of 2.36:1. Car accidents caused 45.4% of tetraplegia cases, falls caused 35.9% of paraplegia cases, and myelitis was the leading cause of non-traumatic SCI. Among paraplegia participants, 65.5% had complete SCI, while 53.1% of tetraplegia participants had incomplete SCI. Functional improvement was reported by 9.58% of participants. Half (50.3%) of the respondents were unemployed, and 75% had incomes below the national average. HRQoL was significantly lower in the SCI population compared to controls, mainly influenced by injury site, income, age and etiology (p

Abstract This study investigated how resting-state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC) predicts antidepressant response in patients with major depressive disorder (MDD). Eighty-seven medication-free MDD patients underwent baseline resting-state functional MRI scans. After 12 weeks of escitalopram treatment, patients were classified into remission depression (RD, n = 42) and nonremission depression (NRD, n = 45) groups. We conducted two analyses: a voxel-wise rsFC analysis using sgACC as a seed to identify group differences, and a prediction model based on the sgACC rsFC map to predict treatment efficacy. Haufe transformation was used to interpret the predictive rsFC features. The RD group showed significantly higher rsFC between the sgACC and regions in the fronto-parietal network (FPN), including the bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral inferior parietal lobule (IPL), compared to the NRD group. These sgACC rsFC measures correlated positively with symptom improvement. Baseline sgACC rsFC also significantly predicted treatment response after 12 weeks, with a mean accuracy of 72.64% (p

Digital light processing (DLP)-based bioprinting technology holds immense promise for the advancement of hydrogel constructs in biomedical applications. However, creating high-performance hydrogel constructs with this method is still a challenge, as it requires balancing the physicochemical properties of the matrix while also retaining the cellular activity of the encapsulated cells. Herein, we propose a facile and practical strategy for the 3D bioprinting of high-performance hydrogel constructs through the in-situ birth of stem cell spheroids. The strategy is achieved by loading the cell/dextran microdroplets within gelatin methacryloyl (GelMA) emulsion, where dextran functions as a decoy to capture and aggregate the cells for bioprinting while GelMA enables the mechanical support without losing the structural complexity and fidelity. Post-bioprinting, the leaching of dextran results in a smooth curved surface that promotes in-situ birth of spheroids within hydrogel constructs. This process significant enhances differentiation potential of encapsulated stem cells. As a proof-of-concept, we encapsulate dental pulp stem cells (DPSCs) within hydrogel constructs, showcasing their regenerative capabilities in dentin and neovascular-like structures in vivo. The strategy in our study enables high-performance hydrogel tissue construct fabrication with DLP-based bioprinting, which is anticipated to pave a promising way for diverse biomedical applications.

Abstract: To investigate the differential expression of the chemokine signaling pathway in lacrimal gland benign lymphoepithelial lesion (LGBLEL) and lacrimal lymphoma, providing insights into the mechanisms underlying malignant transformation and aiding clinical differentiation. Transcriptome analysis was conducted on patients with LGBLEL, lymphoma, and orbital cavernous hemangioma (CH). Three cases of LGBLEL and three cases of lymphoma were randomly selected as control and experimental groups, respectively. A real-time quantitative polymerase chain reaction (RT-qPCR) was used to validate genes associated with the chemokine signaling pathway. Immunohistochemical (IHC) staining and quantitative Western blotting (WB) were performed for precise protein quantification. Transcriptome analysis revealed differential expression of the chemokine signaling pathway between the LGBLEL and lymphoma groups, identifying ten differentially expressed genes: CCL17, VAV2, CXCR5, NRAS, HCK, RASGRP2, PREX1, GNB5, ADRBK2, and CCL22. RT-qPCR showed that, compared to the lymphoma group, the LGBLEL group had significantly higher expression of CCL28, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.001, CCR1 (p = 0.002). IHC staining and quantitative analysis confirmed significant differences in protein expression between the groups for CCL28, CCR1, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.003, 0.011, 0.001, 0.024, 0.005, 0.019, and 0.031, respectively). While IHC provided localization, WB offered greater precision. WB revealed that, compared to the lymphoma group, the LGBLEL group exhibited significantly higher expression of CCL28, CXCL17, HCK, GNB5, NRAS, and VAV2 (p = 0.012, 0.005, 0.009, 0.011, 0.008, and 0.003, respectively) and lower expression of CCR1 (p = 0.014). The chemokine signaling pathway plays a role in the malignant transformation of LGBLEL. The decreased expression of CCL28 and CXCL17, coupled with the increased expression of CCR1, may be linked to the progression of LGBLEL into lymphoma.

Abstract Backgrounds The use of large language models (LLMs) in medicine can help physicians improve the quality and effectiveness of health care by increasing the efficiency of medical information management, patient care, medical research, and clinical decision-making. Methods We collected 34 frequently asked questions about glucocorticoid-induced osteoporosis (GIOP), covering topics related to the disease’s clinical manifestations, pathogenesis, diagnosis, treatment, prevention, and risk factors. We also generated 25 questions based on the 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis (2022 ACR-GIOP Guideline). Each question was posed to the LLM (ChatGPT-3.5, ChatGPT-4, and Google Gemini), and three senior orthopedic surgeons independently rated the responses generated by the LLMs. Three senior orthopedic surgeons independently rated the answers based on responses ranging between 1 and 4 points. A total score (TS) > 9 indicated ‘good’ responses, 6 ≤ TS ≤ 9 indicated ‘moderate’ responses, and TS

Abstract Background The aim of the present study was to investigate the function of novel circular RNA hsa_circ_0036683 (circ‐36683) in non‐small cell lung cancer (NSCLC). Methods RNA sequencing was used to screen out differentially expressed miRNAs. Expression levels of miR‐4664‐3p and circ‐36683 were evaluated in lung carcinoma cells and tissues by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). The effects of miR‐4664‐3p and circ‐36683 on proliferation and migration were assessed using cell counting kit‐8 (CCK‐8), wound healing and transwell migration assays and xenograft experiments. The targeting relationship of circ‐36683/miR‐4664‐3p/CDK2AP2 was assessed by luciferase reporter assays, western blot, qRT‐PCR and argonaute2‐RNA immunoprecipitation (AGO2 RIP). Co‐immunoprecipitation (Co‐IP), 5‐ethynyl‐2′‐deoxyuridine (EdU) staining and CCK‐8 were used to validate the indispensable role of CDK2AP2 in suppressing cell proliferation as a result of CDK2AP1 overexpression. Results By RNA sequencing, miR‐4664‐3p was screened out as an abnormally elevated miRNA in NSCLC tissues. Transfection of miR‐4664‐3p could promote cell proliferation, migration and xenograft tumor growth. As a target of miR‐4664‐3p, CDK2AP2 expression was downregulated by miR‐4664‐3p transfection and CDK2AP2 overexpression could abolish the proliferation promotion resulting from miR‐4664‐3p elevation. Circ‐36683, derived from back splicing of ABHD2 pre‐mRNA, was attenuated in NSCLC tissue and identified as a sponge of miR‐4664‐3p. The functional study revealed that circ‐36683 overexpression suppressed cell proliferation, migration and resulted in G0/G1 phase arrest. More importantly, the antioncogenic function of circ‐36683 was largely dependent on the miR‐4664‐3p/CDK2AP2 axis, through which circ‐36683 could upregulate the expression of p53/p21/p27 and downregulate the expression of CDK2/cyclin E1. Conclusion The present study revealed the antioncogenic role of circ‐36683 in suppressing cell proliferation and migration and highlighted that targeting the circ‐36683/miR‐4664‐3p/CDK2AP2 axis is a promising strategy for the intervention of NSCLC.

Abstract Background The selection of suitable culture medium is critical for achieving good clinical outcomes in cell therapy. To support the commercial application of stem cell therapy, customized culture media not only need to promote stem cell proliferation, but also need to save costs and meet industrial requirements for inter-batch consistency, efficacy, and biosafety. In this study, we developed a series of serum-free media (SFM) and elucidated the effects between different SFM, as well as between SFM and serum-containing meida (SCM), on human umbilical cord mesenchymal stem cells (hUC-MSCs) phenotype and function. We analyze and emphasize from the perspectives of clinical and commercial application why research on customized culture media is critical for the success of enterprises developing novel cellular therapeutics. Methods We cultured hUC-MSCs with identical cell seeding densities in different formulations of SFM and SCM until passage 10 and examined the changes in cell phenotype and function. We analyzed the results with the commercial application requirments of the cellular therapy industry to assess the potential impact of customized culture media on inter-batch consistency, efficacy, stability, biosafety, and cost-effectiveness of industrial-scale cell production. Results hUC-MSCs cultured in SCM and SFM exhibit consistent cell morphology and surface molecule expression, but hUC-MSCs cultured in SFM demonstrate higher activity, superior proliferative capacity, and greater stability. Furthermore, hUC-MSCs cultured in different SFM exhibit differences in cell activity, proliferative capacity, senescent rate, and S/M ratio of cell cycle, while maintaining a normal karyotype after long-term in vitro cultivation. Moreover, we found that hUC-MSCs cultured in different media exhibit variations in paracrine capacity and in their support of hematopoietic stem cell (HSC) self-renewal. Conclusion Considering the substantial funding and time required for cell-based drug development, our results underscore the importances of comprehensively optimizing the composition of medium for the specific disease prior to conducting clinical trials of cell-based therapies. The criteria for selecting culture medium should be based on the requirements of the target disease for cellular function. In addition, we provide a way to formulate different customized SFM, which is beneficial for the development of cell therapy industry.

Abstract Background Axillary lymph node dissection (ALND) is the standard axillary management for breast cancer patients with positive sentinel lymph node biopsy (SLNB) after neoadjuvant therapy. Nevertheless, when that happens, the frequency of additional positive nodes is not properly evaluated. We aim to develop a prediction model to assess the frequency of additional nodal disease after a positive sentinel lymph node following neoadjuvant therapy. Methods We retrospectively analyzed the ultrasound and clinicopathological characteristics of breast cancer patients with 1–3 positive sentinel lymph nodes (SLN) undergoing mastectomy after neoadjuvant therapy (NAT) at our institution, and performed univariate and multivariate logistic analyses to confirm the factors affecting non-SLN metastasis. These factors were included to establish a nomogram, and the area under receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were utilized to assess the validity of this model. Results A total of 126 breast cancer patients were ultimately included in our study, 38 (53.5%) patients were diagnosed with non-SLN metastases of all 71 patients in training set. The results of multifactorial logistic analysis suggested that lymph node metastasis ratio (LNR), short axis of lymph node and progesterone receptor (PR) were strongly associated with non-SLN metastasis. We established a nomogram using the above three variables as predictors, which yielded an area under the curve of 0.795, and validated with a favorable AUC of 0.876. Conclusion The nomogram we constructed can accurately predict the likelihood of non-SLN metastasis in our patients with 1–3 positive SLN after NAT, which may help guide decision making regarding axillary management.

Abstract To assess the effects of a time-restricted feeding (TRF) regimen on meat quality of pigs exposed to high ambient temperature, a two-month feeding and heat treatment (HT) trial was conducted using a 2 × 2 factorial design. A total of 24 growing pigs (11.0 ± 1.9 kg) were randomly divided into four groups: thermal neutral group (NT, 24 ± 3 °C), HT group (exposed to a high temperature at 35 ± 2 °C from 11:00 to 15:00), TRF group and HT + TRF group (HT and TRF co-treatment group, n = 6 for each group). Pigs in TRF groups got access to feed within 5 h from 9:00 to14:00, while the others were fed at 6:00, 11:30, and 16:00. All pigs received the same diet during the trail. The results showed that HT increased the drip loss, shear force, lightness, and malondialdehyde production in Longissimus thoracis et lumborum (LTL) muscle. TRF reversely reduced the shear force and drip loss, accompanied by decreased intramuscular fat and increased moisture content. Enhanced fiber transformation from type 1 to type 2b and down-regulated expression of muscle growth-related genes were observed by HT, while TRF suppressed the fiber transformation and expression of muscle atrophy-related genes. Furthermore, TRF restored the diminished protein expressions of Nrf2 and HO-1 in LTL muscle by chronic HT. Accumulation of HSP70 in muscle of HT group was reduced by treatment of TRF. HT declined the expression of vital genes involved in fatty acids poly-desaturation and the proportion of (polyunsaturated fatty acids) PUFAs, mainly omega-6 in LTL muscle, while TRF group promoted the expression of poly-desaturation pathway and displayed the highest proportion of PUFAs. These results demonstrated that TRF relieved the chronic high temperature affected meat quality by the restored expression of Nrf2/HO-1 anti-oxidative cascade, modified muscle fiber composition, and enriched PUFAs in LTL muscle.

Repairing defects in titanium alloy components is economically justified due to their high cost. In this work, Ti–6Al–4V samples with large area hole defects are repaired by transient liquid-phase sintering. The microstructure and tensile properties after repair have been investigated. The factors of different base powder morphology and the ratio of braze metal are also studied. The results show that by using spherical Ti64 alloy powder with 40 wt% TiZrCuNi braze alloy powder, an overall repair effect with high-density repair zone and good interface combination can be obtained at 960 °C for 3 h. The tensile strength of the as-repaired exceeds that of the matrix, but the elongation is lower than that of the matrix. Finally, the repair experiment conducted at various angles demonstrates this technique's strong practical feasibility.

Abstract Citrullination plays an essential role in various physiological or pathological processes, however, whether citrullination is involved in regulating tumour progression and the potential therapeutic significance have not been well explored. Here, we find that peptidyl arginine deiminase 4 (PADI4) directly interacts with and citrullinates hypoxia-inducible factor 1α (HIF-1α) at R698, promoting HIF-1α stabilization. Mechanistically, PADI4-mediated HIF-1αR698 citrullination blocks von Hippel-Lindau (VHL) binding, thereby antagonizing HIF-1α ubiquitination and subsequent proteasome degradation. We also show that citrullinated HIF-1αR698, HIF-1α and PADI4 are highly expressed in hepatocellular carcinoma (HCC) tumour tissues, suggesting a potential correlation between PADI4-mediated HIF-1αR698 citrullination and cancer development. Furthermore, we identify that dihydroergotamine mesylate (DHE) acts as an antagonist of PADI4, which ultimately suppresses tumour progression. Collectively, our results reveal citrullination as a posttranslational modification related to HIF-1α stability, and suggest that targeting PADI4-mediated HIF-1α citrullination is a promising therapeutic strategy for cancers with aberrant HIF-1α expression.

Objective This study investigated the effects of Apidaecin Api-PR19 as feed additive on growth performance, intestinal health, and small intestinal microbiota of broilers. Methods A total of 360 1-d-old Arbor Acres broilers were randomly assigned to 3 groups with 6 replicates including control group with basal diet (CON), antibiotic growth promotor group with basal plus 10 mg/kg colistin sulfate and 50 mg/kg roxarsone (AGP), and antibacterial peptide group with basal diet plus 330 mg/kg Apidaecin Api-PR19 (ABP). The trial lasted 35 d. Results Results showed that dietary Api-PR19 addition increased (p

AIM: To assess the clinical presentations and outcomes of idiopathic orbital inflammatory pseudotumor (IOIP) patients with orbital wall bone destruction (OWBD) and to propose an expanded classification system that includes bone destruction. METHODS: The study retrospectively reviewed clinical presentations, imaging findings, treatment modalities, and outcomes of six patients diagnosed histopathologically with IOIP and OWBD at the Beijing Tongren Hospital, Capital Medical University between October 2018 and June 2021. RESULTS: Over two years, 6 (10%) of 60 IOIP patients at our hospital exhibited OWBD, but this may overrepresent severe cases. The cohort consisted of three men and three women, aged 17 to 60y (mean 35.5±16.1y). Presenting symptoms included proptosis, eyelid swelling, decreased visual acuity with pain, and palpable mass. Imaging revealed multiple anatomical structures involved with the medial wall being the most common site of bone destruction. Histopathological examination showed classic type in five patients and sclerosing type in one patient. All patients underwent surgical resection followed by methylprednisolone treatment. Follow-up (mean 30.3±3.1mo) indicated three patients had no recurrence, while others had varying degrees of symptom persistence or recurrence. CONCLUSION: IOIP with bone destruction is a rare but significant subtype that mimics malignancy, leading to potential diagnostic and therapeutic challenges. Our findings suggest that complete surgical resection combined with adjunctive glucocorticoid therapy can yield favorable outcomes. However, larger-scale studies are needed to further optimize therapeutic approaches.

Abstract Objectives To retrospectively investigate clinical characterization and the long-term postoperative outcomes of retinoblastoma (RB) patients receiving enucleation with primary orbital implantation in early infancy (0–6 months old). Methods The clinical and follow-up data of 42 RB patients receiving enucleation with primary orbital implantation in early infancy at Beijing Tongren Hospital from December 2009 to January 2020 were analysed. The average follow-up time was 83 months. The patient group included 24 males and 18 females, 30 unilateral and 12 bilateral cases. A total of 44 eyes with 10 in stage D and 34 in stage E underwent 40 unilateral and 2 bilateral surgeries. 17 RB eyes received hydrogel and 27 RB eyes received hydroxyapatite implants. This study was performed by following the guideline of STROBE. Results Enucleation combined with primary orbital implantation promoted survival and was safe with few and minor complications such as increased secretion, upper eyelid ptosis, and sunken eye sockets which were not affected by stages, lateralities, or implant materials. 55-80% RB patients exhibited satisfactory appearance and obvious or moderate motility of orbital implants according to the evaluation by doctors and family members. Family members were likely more optimistic about the appearance and more pessimistic about motility of the orbital implantation than doctors did.The quality of life was high as indicated by PedsQL3.0 or PedsQL4.0 scores ( ≧ 90 for > 75% patients). It was not affected by the stages, laterality, and implant materials, nor affected by the appearance and motility of the implants. Conclusions The outcomes of the combination of enucleation and primary orbital implantation for pertinent RB patients in early infancy are generally satisfactory with few and minor complications, high safety, appearance, and overall quality of life. Enucleation combined with primary orbital implantation in early infancy benefits pertinent RB patients in appearance, survival, and quality of life.

Abstract We systematically investigate the mass spectrum and two-body open-charm strong decays of charmonium states in a coupled-channel model where the $$^3P_0$$ 3 P 0 quark-antiquark pair creation mechanism is employed. The results of masses, mass shifts, proportions of the $$c\bar{c}$$ c c ¯ component, and open-charm decay widths are provided. The S-D wave mixing angles and di-electric decay widths for vector mesons are also presented. Based on our results, we find that the $$\psi (3770)$$ ψ ( 3770 ) , $$\psi (4040)$$ ψ ( 4040 ) , $$\psi (4160)$$ ψ ( 4160 ) , $$\psi (4360)$$ ψ ( 4360 ) , and $$\psi (4415)$$ ψ ( 4415 ) can be assigned as the $$1^3D_1$$ 1 3 D 1 -, $$3^3S_1$$ 3 3 S 1 -, $$2^3D_1$$ 2 3 D 1 -, $$4^3S_1$$ 4 3 S 1 -, and $$3^3D_1$$ 3 3 D 1 -dominated charmonium states, respectively. The $$\psi _3(3842)$$ ψ 3 ( 3842 ) is a good candidate of the $$\psi _3(1D)$$ ψ 3 ( 1 D ) charmonium state. The calculated mass and strong decay width of $$\chi _{c1}(2P)$$ χ c 1 ( 2 P ) with significant continuum contribution ( $$\sim $$ ∼ 57%) favor the charmonium interpretation for the mysterious $$\chi _{c1}(3872)$$ χ c 1 ( 3872 ) . When considering the large uncertainty in the observed decay width, the possibility to assign the $$\chi _{c0}(3860)$$ χ c 0 ( 3860 ) as the $$\chi _{c0}(2P)$$ χ c 0 ( 2 P ) charmonium state cannot be ruled out. One may describe well the properties of $$\chi _{c2}(3930)$$ χ c 2 ( 3930 ) with the $$\chi _{c2}(2P)$$ χ c 2 ( 2 P ) charmonium. The predictions on properties of other $$c\bar{c}$$ c c ¯ states can be tested by future experiments.

Abstract Background Aedes albopictus is an important vector for pathogens such as dengue, Zika, and chikungunya viruses. While insecticides is the mainstay for mosquito control, their widespread and excessive use has led to the increased resistance in Ae. albopictus globally. Gut symbiotic bacteria are believed to play a potential role in insect physiology, potentially linking to mosquitoes’ metabolic resistance against insecticides. Methods We investigated the role of symbiotic bacteria in the development of resistance in Ae. albopictus by comparing gut symbiotic bacteria between deltamethrin-sensitive and deltamethrin-resistant populations. Adults were reared from field-collected larvae. Sensitive and resistant mosquitoes were screened using 0.03% and 0.09% deltamethrin, respectively, on the basis of the World Health Organization (WHO) tube bioassay. Sensitive and resistant field-collected larvae were screened using 5 × LC50 (lethal concentration at 50% mortality) and 20 × LC50 concentration of deltamethrin, respectively. Laboratory strain deltamethrin-sensitive adults and larvae were used as controls. The DNA of gut samples from these mosquitoes were extracted using the magnetic bead method. Bacterial 16S rDNA was sequenced using BGISEQ method. We isolated and cultured gut microorganisms from adult and larvae mosquitoes using four different media: Luria Bertani (LB), brain heart infusion (BHI), nutrient agar (NA), and salmonella shigella (SS). Results Sequencing revealed significantly higher gut microbial diversity in field-resistant larvae compared with field-sensitive and laboratory-sensitive larvae (P

Abstract Purpose This current study attempted to investigate whether one-stitch method (OM) of temporary ileostomy influenced the stoma-related complications after laparoscopic low anterior resection (LLAR). Methods We searched for eligible studies in four databases including PubMed, Embase, Cochrane Library, and CNKI from inception to July 20, 2023. Both surgical outcomes and stoma-related complications were compared between the OM group and the traditional method (TM) group. The Newcastle–Ottawa Scale (NOS) was adopted for quality assessment. RevMan 5.4 was conducted for data analyzing. Results Totally 590 patients from six studies were enrolled in this study (272 patients in the OM group and 318 patients in the TM group). No significant difference was found in baseline information (P > 0.05). Patients in the OM group had shorter operative time in both the primary LLAR surgery (MD = − 17.73, 95%CI = − 25.65 to − 9.80, P

Abstract Semantic segmentation of point cloud data of architectural cultural heritage is of significant importance for HBIM modeling, disease extraction and analysis, and heritage restoration research fields. In the semantic segmentation task of architectural point cloud data, especially for the protection and analysis of architectural cultural heritage, the previous deep learning methods have poor segmentation effects due to the complexity and unevenness of the data, the high geometric feature similarity between different components, and the large scale changes. To this end, this paper proposes a novel encoder-decoder architecture called DSC-Net. It consists of an encoder-decoder structure based on point random sampling and several fully connected layers for semantic segmentation. To overcome the loss of key features caused by random downsampling, DSC-Net has developed two new feature aggregation schemes: the enhanced dual attention pooling module and the global context feature module, to learn discriminative features for the challenging scenes mentioned above. The former fully considers the topology and semantic similarity of neighboring points, generating attention features that can distinguish categories with similar structures. The latter uses spatial location and neighboring volume ratio to provide an overall view of different types of architectural scenes, helping the network understand the spatial relationships and hierarchical structures between different architectural elements. The proposed modules can be easily embedded into various network architectures for point cloud semantic segmentation. We conducted experiments on multiple datasets, including the ancient architecture dataset, the ArCH architectural cultural heritage dataset, and the publicly available architectural segmentation dataset S3DIS. The results show that the mIoU reached 63.56%, 55.84%, and 71.03% respectively. The experimental results prove that our method has the best segmentation effect in dealing with challenging architectural cultural heritage data and also demonstrates its practicality in a wider range of architectural point cloud segmentation applications.

Sweetness is an important driver for food intake and one of the most popular taste sensations. At present, there is a preliminary understanding of the signaling pathways of sweetness and the mechanisms that affect sweetness sensation. Human sweetness sensation is expressed through at least two types of signaling pathways, one of which is mediated by heterodimers formed by the taste receptor family 1 member 2 (T1R2) and the taste receptor family 1 member 3 (T1R3), whereas the other by sodium glucose co-transporters (SGLT) and glucose transporters (GLUT). This article reviews the structure of T1R2/T1R3 heterodimer and the mechanism of sweet signal transduction, and discusses the effects of internal and external factors such as bitterness, sourness, umami, anti-sweetness substances, aroma compounds, saliva, obesity and age on sweetness sensation. The shortcomings of the current research are presented, such as little effect of the current available noncaloric sweeteners (NCSs) in attenuating obesity and diabetes, few studies on the interactions of sweet taste with the other four taste sensations, unclear understanding of the molecular basis of the regulation mechanisms of anti-sweetness substances at the receptor level, and limitations of using rodents as an experimental substitute for humans in sweet taste research. This article aims to understand how sweet substances exert their functions in complex food matrices, hoping to provide theoretical support and ideas for future development and application of NCS-containing foods.

The Triassic Baikouquan Formation glutenite in the Junggar Basin of western China is rich in tight oil resources. Due to the presence of gravels with varying composition and strength in the glutenite, the mechanical characteristics of the glutenite are significantly affected by the shape, size, and physical properties of the gravels, which in turn affects the fracture complexity and fracturing reconstruction effectiveness of the glutenite reservoirs. In view of this, a method for generating random irregular polygonal gravels was established based on the reservoir characteristics of Baikouquan Formation, Junggar Basin. A mechanical numerical model of the glutenite was created based on particle discrete element method to study the influence mechanism of typical gravel content and distribu-tion on the meso-mechanical characteristics of glutenite. The results show that low-strength gravels have a weak shielding effect on fracture propagation, with most cracks exhibiting a "penetrating gravel" pattern. In contrast, high-strength gravels exhibit a stronger shielding effect, leading to more "bypass gravel" fracture patterns. With increased confining pressure, the compressive strength of the rock significantly increases, along with peak strain energy and slip energy, both showing a linear increase with strain energy being particularly pronounced. In glutenite reservoirs with different gravel combinations, there is a strong linear relationship between the number of shear microcracks and the confining pressure. The glutenite reservoirs with high confining pressure and high-strength gravels exhibit more obvious plastic and ductile characteristics, along with evident secondary failure phenomena. With the decrease of low-strength gravels or the increase of high-strength gravels, the elastic modulus of the glutenite increases, enhancing its resistance to deformation. However, the influence of confining pressure on the elastic modulus of glutenite is minimal across different gravel combinations. The formation and development of macroscopic failure zones in glutenite are largely controlled by the internal meso-structure and are greatly affected by confining pressure and gravel type (mechanical strength).

Abstract The current study aimed to evaluate the effect of lymph node ratio (LNR) on the short-term and long-term outcomes of colorectal cancer (CRC) patients who underwent radical CRC surgery. We retrospectively collected CRC patients who underwent radical surgery from Jan 2011 to Jan 2020 in a single-center hospital. The patients were divided into the high LNR group and the low group according to the median. The baseline information and the short-term outcomes were compared between the high group and the low group. Univariate and multivariate logistic regression was performed to analyze the independent predictors for overall survival (OS) and disease-free survival (DFS). A 1:1 proportional propensity score matching (PSM) was used to reduce the selection bias between the two groups. Kaplan–Meier method was used to estimate the OS and DFS between the two groups in different T stages. A total of 1434 CRC patients undergoing radical surgery were enrolled in this study, and there were 730 (50.9%) patients in the low LNR group and 704 (49.1%) patients in the high LNR group. After the PSM, there were 618 patients in both groups, the baseline characteristics between the two groups had no significant difference (p > 0.05). After comparing the Surgery-related information and The Short-term outcomes, the high LNR group had a longer hospital stay (after PSM, p

Abstract Background The different symptoms of major depressive disorder (MDD) in adolescents compared to adults suggested there may be differences in the pathophysiology between adolescents and adults with MDD. However, despite the amygdala being considered critical in the pathophysiology, there was limited knowledge about the commonalities and differences in the resting-state functional connectivity (rsFC) of amygdala subregions in MDD patients of different age groups. Methods In the current study, 65 adolescents (46 with MDD and 19 controls) and 91 adults (35 with MDD and 56 controls) were included. A seed-based functional connectivity analysis was performed for each of the amygdala subregions. A 2 × 2 ANOVA was used to analyze the main effect of age, diagnosis, and their interaction on the rsFC of each subregion. Results A significant main effect of age was revealed in the rsFC of bilateral centromedial (CM) subregions and right laterobasal (LB) subregion with several brain regions in the limbic system and frontoparietal network. The significant main effect of diagnosis showed MDD patients of different ages showed higher connectivity than controls between the right LB and left middle frontal gyrus (MFG). Conclusions The rsFC of specific amygdala subregions with brain regions in the limbic system and frontoparietal network is affected by age, indicating a distinct amygdala connectivity profile in adolescents. The decreased rsFC between the right LB and the left MFG in adolescents and adults with MDD could serve as a diagnostic biomarker and a target of nonpharmacological treatment for MDD.

Abstract Background Maternal diabetes mellitus can influence the development of offspring. Gestational diabetes mellitus (GDM) creates a short-term intrauterine hyperglycaemic environment in offspring, leading to glucose intolerance in later life, but the long-term effects and specific mechanism involved in skeletal muscle dysfunction in offspring remain to be clarified. Methods Pregnant mice were divided into two groups: The GDM group was intraperitoneally injected with 100 mg/kg streptozotocin on gestational days (GDs) 6.5 and 12.5, while the control (CTR) group was treated with vehicle buffer. Only pregnant mice whose random blood glucose level was higher than 16.8 mmol/L beginning on GD13.5 were regarded as the GDM group. The growth of the offspring was monitored, and the glucose tolerance test was performed at different time points. Body composition analysis and immunohistochemical methods were used to evaluate the development of lean mass at 8 weeks. The exercise capacity and grip strength of the male mouse offspring were assessed at the same period. Transmission electron microscopy was used to observe the morphology inside skeletal muscle at 8 weeks and as a foetus. The genes and proteins associated with mitochondrial biogenesis and oxidative metabolism were investigated. We also coanalyzed RNA sequencing and proteomics data to explore the underlying mechanism. Chromatin immunoprecipitation and bisulfite-converted DNA methylation detection were performed to evaluate this phenomenon. Results Short-term intrauterine hyperglycaemia inhibited the growth and reduced the lean mass of male offspring, leading to decreased endurance exercise capacity. The myofiber composition of the tibialis anterior muscle of GDM male offspring became more glycolytic and less oxidative. The morphology and function of mitochondria in the skeletal muscle of GDM male offspring were destroyed, and coanalysis of RNA sequencing and proteomics of foetal skeletal muscle showed that mitochondrial elements and lipid oxidation were consistently impaired. In vivo and in vitro myoblast experiments also demonstrated that high glucose concentrations impeded mitochondrial organisation and function. Importantly, the transcription of genes associated with mitochondrial biogenesis and oxidative metabolism decreased at 8 weeks and during the foetal period. We predicted Ppargc1α as a key upstream regulator with the help of IPA software. The proteins and mRNA levels of Ppargc1α in the skeletal muscle of GDM male offspring were decreased as a foetus (CTR vs. GDM, 1.004 vs. 0.665, p = 0.002), at 6 weeks (1.018 vs. 0.511, p = 0.023) and 8 weeks (1.006 vs. 0.596, p = 0.018). In addition, CREB phosphorylation was inhibited in GDM group, with fewer activated pCREB proteins binding to the CRE element of Ppargc1α (1.042 vs. 0.681, p = 0.037), Pck1 (1.091 vs. 0.432, p = 0.014) and G6pc (1.118 vs. 0.472, p = 0.027), resulting in their decreased transcription. Interestingly, we found that sarcopenia and mitochondrial dysfunction could even be inherited by the next generation. Conclusions Short-term intrauterine hyperglycaemia significantly reduced lean mass in male offspring at 8 weeks, resulting in decreased exercise endurance and metabolic disorders. Disrupted organisation and function of the mitochondria in skeletal muscle were also observed among them. Foetal exposure to hyperglycaemia decreased the ratio of phosphorylated CREB and reduced the transcription of Ppargc1α, which inhibited the transcription of downstream genes involving in mitochondrial biogenesis and oxidative metabolism. Abnormal mitochondria, which might be transmitted through aberrant gametes, were also observed in the F2 generation.

Abstract Objective To examine the clinical characteristics, diagnosis and treatment, and prognosis of ocular amyloidosis in a Chinese population. Methods A retrospective case series study was conducted. The clinical data of 37 patients with ocular amyloidosis were collected and the clinical characteristics, diagnosis and treatment, and prognosis were summarized and analyzed. Results The 37 patients included 12 males and 25 females ranging in age from 22 to 75 years, with median age of 49 years. The clinical signs and symptoms included a conjunctival mass in 37 patients (100%), periorbital discomfort or pain in 29 patients (61.9%), ptosis in 18 patients (23.8%), exophthalmos or eyeball displacement in 3 patients (14.3%), restricted eye movement in 2 patients (9.52%), vision loss in 1 patient (4.76%), and diplopia in 1 patient (4.76%). A total of 29 patients had only conjunctival involvement and 8 patients had concomitant orbital and conjunctival involvement. The main treatment for patients with conjunctival involvement was surgical resection. Thirty-one patients had stable disease, 4 patients progressed or relapsed, and 2 patients were lost to follow-up. Conclusion Ocular amyloidosis most commonly presents as an eyelid or conjunctival mass or diffuse thickening and can also present as an orbital mass. Diagnosis is mainly dependent on histopathological examination. Surgery is the main treatment and is done to confirm the diagnosis to guide further treatment, preserve function, and prevent complications that threaten visual acuity. Close postoperative follow-up is necessary.

Abstract Background The prognostic value of triglyceride-glucose (TyG) related indices in non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is still unclear. This study aimed to determine the associations between TyG-related indices and long-term mortality in this population. Methods The data came from the National Health and Nutrition Examination Survey (NHANES III) and National Death Index (NDI). Baseline TyG, TyG combining with body mass index (TyG-BMI), and TyG combining with waist circumference (TyG-WC) indices were calculated, and mortality status was determined through 31 December 2019. Multivariate Cox and restricted cubic spline (RCS) regression models were performed to evaluate the relationship between TyG-related indices and long-term mortality among participants with NAFLD/MASLD. In addition, we examined the association between TyG-related indices and all-cause mortality within subgroups defined by age, sex, race/ethnicity, and fibrosis-4 index (FIB-4). Results There were 10,390 participants with completed ultrasonography and laboratory data included in this study. NAFLD was diagnosed in 3672/10,390 (35.3%) participants, while MASLD in 3556/10,390 (34.2%) amongst the overall population. The multivariate Cox regression analyses showed high levels of TyG-related indices, particularly in TyG-BMI and TyG-WC indices were significantly associated with the all-cause mortality, cardiovascular mortality, and diabetes mortality in either NAFLD or MASLD. The RCS curves showed a nonlinear trend between three TyG-related indices with all-cause mortality in either NAFLD or MASLD. Subgroup analyses showed that TyG-BMI and TyG-WC indices were more suitable for predicting all-cause mortality in patients without advanced fibrosis. Conclusion Our study highlights the clinical value of TyG-related indices in predicting the survival of the NAFLD/MASLD population. TyG-BMI and TyG-WC indices would be the surrogate biomarkers for the follow-up of the population without advanced fibrosis.

Abstract Prolonged ventricular repolarization has been associated with cardiovascular disease. We sought to investigate the association of prolonged ventricular repolarization with mild cognitive impairment (MCI) and the potential underlying neuropathological mechanisms in older adults. This cross-sectional study included 4328 dementia-free participants (age ≥ 65 years; 56.8% female) in the baseline examination of the Multidomain INterventions to delay dementia and Disability in rural China; of these, 989 undertook structural brain magnetic resonance imaging (MRI) scans. QT, QTc, JT, JTc, and QRS intervals were derived from 12-lead electrocardiograph. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were defined following the Petersen’s criteria. Volumes of gray matter (GM), white matter, cerebrospinal fluid, total white matter hyperintensities (WMH), periventricular WMH (PWMH), and deep WMH (DWMH) were automatically estimated. Data were analyzed using logistic and general linear regression models. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with an increased likelihood of MCI and aMCI, but not naMCI (p

Currently, practical applications of shape memory alloy (SMA) solid elastocaloric refrigeration materials are limited by low elastocaloric effect (eCE), high applied stress, and large stress hysteresis (Δσhys). Here, we introduce a composition design strategy using Ti-doped Co–V-Ga SMAs to address these challenges. We combine first-principles calculations and experiments to verify this strategy. Our results show that the lattice distortion caused by the significant difference in atomic radius after Ti doping produces a solid solution strengthening effect inside the alloy, which significantly improves the superelasticity of the alloy, delays the plastic deformation of the austenite phase, and the volume fraction of martensitic transformation increases significantly. The newly developed Co51.7V31.3Ga16Ti1 bulk polycrystalline alloy exhibits a remarkable adiabatic temperature change (ΔTad) of −10 K at room temperature under a low stress of 400 MPa, a minimum Δσhys of 18 MPa, and a high coefficient of performance COPmat of 31.9. Importantly, the 100-cycle loading-unloading test at 350 MPa is done, and it reveals that the ΔTad for the Ti0 alloy was only 3.9 K, while it reached 6.2 K for the Ti1 alloy, marking a noteworthy 59 % performance enhancement. From the simplicity of the fabrication process to the comprehensive performance of the material, it exhibits a promising advantage for practical cooling applications This study presents a feasible design strategy for large-scale production of high-performance bulk polycrystalline alloys with high eCE, low stress, and Δσhys.

ABSTRACT: The health benefits conferred by probiotics is specific to individual probiotic strains, highlighting the importance of identifying specific strains for research and production purposes. Streptococcus thermophilus CICC 6038 and Lactobacillus delbrueckii ssp. bulgaricus CICC 6047 are exceedingly valuable for commercial use with an excellent mixed-culture fermentation. To differentiate these 2 strains from other S. thermophilus and L. delbrueckii ssp. bulgaricus, a specific, sensitive, accurate, rapid, convenient, and cost-effective method is required. In this study, we conducted a pan-genome analysis of S. thermophilus and L. delbrueckii ssp. bulgaricus to identify species-specific core genes, along with strain-specific SNPs. These genes were used to develop suitable PCR primers, and the conformity of sequence length and unique SNPs was confirmed by sequencing for qualitative identification at the strain level. The results demonstrated that SNPs analysis of PCR products derived from these primers could distinguish CICC 6038 and CICC 6047 accurately and reproducibly from the other strains of S. thermophilus and L. delbrueckii ssp. bulgaricus, respectively. The strain-specific PCR method based on SNPs herein is universally applicable for probiotics identification. It offers valuable insights into identifying probiotics at the strain level that is fit-for-purpose in quality control and compliance assessment of commercial dairy products.

Background: The effect of transcranial alternating current stimulation (tACS) on major depressive disorder (MDD) was not confirmed. Objective: To evaluate the feasibility, safety, and efficacy of tACS as an add-on treatment for the symptoms of depression and to understand how tACS affects brain activity. Methods: The 4-week, double-blind, randomized, sham-controlled trial was performed from January 29, 2023 to December 22, 2023. Sixty-six participants were recruited and randomly assigned to receive 20 40-min sessions of either active (77.5Hz, 15 mA) or sham stimulation, with one electrode on the forehead and two on the mastoid, each day (n = 33 for each group) for four weeks (till Week 4). The participants were followed for 4 more weeks (till Week 8) without stimulation for efficacy/safety assessment. During the 4-week trial, all participants were required to take 10–20 mg of escitalopram daily. The primary efficacy endpoint was the change in HAMD-17 scores from baseline to Week 4 (with 20 treatment sessions completed). Resting-state electroencephalography (EEG) was collected with a 64-channel EEG system (Brain Products, Germany) at baseline and the Week 4 follow-up. The chi-square test, Fisher's exact test, independent-sample t-test, or Wilcoxon rank-sum test were used, as appropriate, to compare the differences in variables between groups. The effect of the intervention on the HAMD-17 score was also evaluated with linear mixed modeling (LMM) as sensitivity analysis. The correlation between the mean reduction in EEG and the mean reduction in the HAMD-17 total score was evaluated using Spearman correlation analysis. Results: A total of 66 patients (mean [SD] age, 28.4 [8.18] years; 52 [78.8 %] female) were randomized, and 57 patients completed the study. Significant differences were found in the reductions in the HAMD-17 scores at Week 4 (t = 3.44, P = 0.001). Response rates at Week 4 were significantly higher in the active tACS group than in the sham tACS group (22 out of 33 patients [66.7 %] versus 11 out of 33 [33.3 %], P = 0.007). In the active tACS group, a correlation between the mean change in alpha power and HAMD-17 scores at Week 4 was found (r = 2.38, P = 0.024), and the mean change in alpha power was significantly bigger for responders (Z = 2.46, P = 0.014). No serious adverse events were observed in this trial. Conclusion: The additional antidepressant effect of tACS is significant, and the combination of tACS with antidepressants is a feasible and effective approach for the treatment of MDD. The antidepressant mechanism of tACS may be the reduction in alpha power in the left frontal lobe. Future research directions may include exploring more appropriate treatment parameters of tACS.

Engineered bacteria have shown great potential in cancer immunotherapy by dynamically releasing therapeutic payloads and inducing sustained antitumor immune response with the crosstalk of immune cells. In previous studies, FOLactis was designed, which could secret an encoded fusion protein of Fms-related tyrosine kinase 3 ligand and co-stimulator OX40 ligand, leading to remarkable tumor suppression and exerting an abscopal effect by intratumoral injection. However, it is difficult for intratumoral administration of FOLactis in solid tumors with firm texture or high internal pressure. For patients without lesions such as abdominal metastatic tumors and orthotopic gastric tumors, intratumoral injection is not feasible and peritumoral maybe a better choice. Herein, an engineered bacteria delivery system is constructed based on in situ temperature-sensitive poloxamer 407 hydrogels. Peritumoral injection of FOLactis/P407 results in a 5-fold increase in the proportion of activated DC cells and a more than 2-fold increase in the proportion of effective memory T cells (TEM), playing the role of artificial lymph island. Besides, administration of FOLactis/P407 significantly inhibits the growth of abdominal metastatic tumors and orthotopic gastric tumors, resulting in an extended survival time. Therefore, these findings demonstrate the delivery approach of engineered bacteria based on in situ hydrogel will promote the efficacy and universality of therapeutics.