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Abstract Plasma spray-physical vapor deposition (PS-PVD) is a promising third-generation thermal barrier coatings (TBCs) technique. Feather-like columnar TBCs with excellent strain tolerance and low thermal conductivity can be achieved using PS-PVD. However, molten CMAS (CaO–MgO–Al2O3–SiO2) can penetrate coatings and accelerate PS-PVD TBCs failure due to the feather-like columnar structure. Hence, a strategy is proposed to alleviate molten CMAS corrosion. The super-hydrophobicity structure is fabricated via laser texturing on the surface of PS-PVD TBCs to repel molten CMAS wetting and spreading. Then, a thin layer of the Al-film is deposited on the laser-textured surface. Next, the Al-modified layer is in situ synthesized after vacuum heat treatment, preventing the infiltration of molten CMAS into the TBCs and reducing the coating damage. The results show that the contact angle of laser textured and Al-modified PS-PVD TBCs (LT-Al) at room temperature increased from 12.3° to 168.8°. The wetting and spreading behavior of molten CMAS of as-sprayed (AS), laser textured (LT), and LT-Al coatings is observed in situ at 1230 °C for 1800 s. The LT-Al coatings exhibited excellent CMAS corrosion resistance, attributed to the laser-textured micro-nano structures and Al-modified layer protection. The findings may be an effective approach for solving the disadvantage of PS-PVD feather-like columnar structure TBCs.

Abstract Background B3GNT7, a glycosyltransferase of significant importance that is highly expressed in intestinal epithelial cells, plays a pivotal role in intestinal physiological processes. This study elucidates novel insights into the potential role and underlying mechanisms of B3GNT7 in ulcerative colitis (UC). Methods An experimental colitis model was induced using DSS in mice to investigate B3GNT7 expression in the colon via transcriptomics and immunohistochemistry. Bioinformatics analysis was employed to delineate the biological functions of B3GNT7. Additionally, the correlation between the transcription levels of B3GNT7 in colonic tissues from patients with UC, sourced from the IBDMDB database, and the severity of colonic inflammation was analyzed to elucidate potential mechanisms. Results The DSS-induced colitis model was successfully established, and transcriptomic analysis identified a marked downregulation of B3GNT7 expression in the colonic tissues compared to the controls. Functional enrichment analysis indicated B3GNT7’s predominant role in mucin O-glycosylation. Protein interaction analysis revealed that B3GNT7 predominantly interacts with members of the mucin MUC family, including MUC2, MUC3, and MUC6. In patients with UC, B3GNT7 transcription levels were significantly reduced, particularly in those with moderate to severe disease activity. The expression level of B3GNT7 exhibited a negative correlation with the endoscopic severity of UC. Gene set enrichment analysis (GSEA) further demonstrated significant enrichment of B3GNT7 in the mucin O-glycosylation synthesis pathway. Conclusion The downregulation of B3GNT7 expression in the colonic tissues of UC patients may contribute to the compromised mucin barrier function and the exacerbation of colitis.

Abstract Background Ultrasound has widely used in various medical fields related to critical care. While online and offline ultrasound trainings are faced by certain challenges, remote ultrasound based on the 5G cloud platform has been gradually adopted in many clinics. However, no study has used the 5G remote ultrasound cloud platform operating system for standardized critical care ultrasound training. This study aimed to evaluate the feasibility and effectiveness of 5G-based remote interactive ultrasound training for standardized diagnosis and treatment in critical care settings. Methods A 5G-based remote interactive ultrasound training system was constructed, and the course was piloted among critical care physicians. From July 2022 to July 2023, 90 critical care physicians from multiple off-site locations were enrolled and randomly divided into experimental and control groups. The 45 physicians in the experimental group were trained using the 5G-based remote interactive ultrasound training system, while the other 45 in the control group were taught using theoretical online videos. The theoretical and practical ultrasonic capabilities of both groups were evaluated before and after the training sessions, and their levels of satisfaction with the training were assessed as well. Results The total assessment scores for all of the physicians were markedly higher following the training (80.7 ± 11.9) compared to before (42.1 ± 13.4) by a statistically significant margin (P

In agriculture, specifically livestock monitoring, drones' ability to track multiple targets is essential for advancing the field. However, limited computing resources and unpredictable drone movements often cause issues like ambiguous video frames, object obstructions, and size deviations. These inconsistencies reduce tracking accuracy, making traditional algorithms inadequate for handling drone footage. This study introduces an enhanced deep learning-based multi-target drone tracker framework that enables real-time processing. The proposed method combines object detection and tracking by leveraging consecutive frame pairs to extract and share features, enhancing computational efficiency. It employs diverse loss functions to address class and sample distribution imbalances and includes a composite deblurring module to enhance detection accuracy. Object association utilizes a dual regress bounding box technique, aiding in object identification verification and predictive motion. Live tracking is achieved by predicting object locations in subsequent frames, enabling real-time tracking. Evaluation against leading benchmarks shows that the system improves precision and speed, achieving a 4.3 % increase in Multi-Object Tracking Accuracy (MOTA) and a 7.7 % boost in F1 score.

Abstract Background Mecapegfilgrastim, a long‐acting granulocyte‐colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. Objective We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S‐1/capecitabine‐based regimens or the fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. Method Five hundred and sixty‐one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. Results The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S‐1/capecitabine‐based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S‐1/capecitabine‐based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. Conclusion In a real‐world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high‐risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.

Background: Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information. Objectives: This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC. Design: We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors. Methods: Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis. Results: In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, p = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002–1.830, p = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, p = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056–2.112, p = 0.023). However, no statistically significant difference in overall survival was observed between the two groups. Conclusion: Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms.

Abstract Background Environmental factors play an important role in developing mental disorders. This study aimed to investigate the associations of metal and nonmetal elements in drinking water with the risk of depression and anxiety and to assess whether diets modulate these associations. Methods We conducted a prospective cohort study including 24,285 participants free from depression and anxiety from the Yinzhou Cohort study in the 2016–2021 period. The exposures were measured by multiplying metal and nonmetal element concentrations in local pipeline terminal tap water samples and total daily drinking water intakes. Cox regression models adjusted for multi-level covariates were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95%CIs). Results During an average follow-up period of 4.72 and 4.68 years, 773 and 1334 cases of depression and anxiety were identified, respectively. A 1 standard deviation (SD) increase in manganese exposure reduced the incidence of depression by 8% (HR 0.92, 95%CI 0.88 to 0.97). In contrast, with a 1 SD increase in copper and cadmium exposure, the incidence of depression increased by 6% (HR 1.06, 95%CI 1.01 to 1.11) and 8% (HR 1.08, 95%CI 1.00 to 1.17), respectively. The incidence of anxiety increased by 39% (HR 1.39, 95%CI 1.20 to 1.62), 33% (HR 1.33, 95%CI 1.03 to 1.71), and 14% (HR 1.14, 95%CI 1.03 to 1.25) respectively for a 1 SD increase in manganese, iron, and selenium exposure. Diets have a moderating effect on the associations of metal and nonmetal elements with the risk of anxiety. Stronger associations were observed in older, low-income groups and low-education groups. Conclusions We found significant associations between exposure to metal and nonmetal elements and depression and anxiety. Diets regulated the associations to some extent.

Abstract Immune checkpoint inhibitor (ICI) rechallenge in non‐small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD‐1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option.

ABSTRACTCongenital heart disease (CHD) represents a significant population warranting particular attention concerning vaccination coverage. To comprehend the vaccination status of CHD within Yinzhou District, Ningbo City, China, and to facilitate the formulation of preventive, control, and immunization strategies against vaccine-preventable diseases in children with congenital heart conditions. Using the China Yinzhou Electronic Health Record Study (CHERRY) database, we analyzed the vaccination coverage of children with CHD born between January 1, 2016 and September 20, 2021, and analyzed the influencing factors associated with the level of vaccination coverage. This study involved 762 children diagnosed with CHD at the age of 12 months, revealing that 86.74% of these children had received at least one dose of the National Immunization Program (NIP) vaccines. The coverage for non-NIP vaccines, such as the rotavirus vaccine, influenza vaccine, Influenza Haemophilus influenzae Type b (Hib) Conjugate Vaccine, 13-valent pneumococcal conjugate vaccine (PCV13), and inactivated enterovirus type 71 vaccine (EV71), stood at 27.30%, 7.74%, 63.25%, 33.76%, and 34.51%, respectively. The completion coverage for the entire vaccination schedule were 27.30%, 5.51%, 55.77%, 34.25%, and 25.59%, respectively. There was a statistically significant correlation between vaccination coverage in classification of diagnostic medical institutions and the types of diagnosed diseases. Compared to their typically developing counterparts, 12-month-old children afflicted with CHD exhibit a slightly diminished vaccination coverage, alongside a discernible inclination toward delayed vaccination. Notably, the determination to undergo vaccinations seems predominantly influenced by the classification of diagnostic medical institutions. In practical terms, proactive measures involving early diagnosis, comprehensive health assessments, and timely interventions ought to be implemented to enhance vaccination rates while prioritizing safety.

AbstractThe conventional use of Heracleum moellendorffii Hance is for wind dispelling and toxin removal. This research aims to enhance the understanding of the flowering aerial parts of this plant by analyzing its volatile oil. Hydrodistillation was employed to extract the essential oil, which was subsequently analyzed using gas chromatography coupled with mass spectrometry. The analysis revealed the presence of 50 compounds, which accounted for 92.67% of the oil’s composition. The major constituents include germacrene D (21.78%), n-octyl acetate (19.57%), β-caryophyllene (7.35%), and octyl butyrate (4.36%). The antioxidant potential of the volatile oil was evaluated through six separate experiments, demonstrating significant scavenging abilities against 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (IC50, 62.7 μg/mL), hydroxyl radicals (IC50, 1611.1 μg/mL), and superoxide radicals (16.8%). However, it exhibited weak scavenging activity against 2,2-diphenyl-1-picryl hydrazyl (IC50, 5827.0 μg/mL), and had low FRAP values. No CUPRAC activity was observed. Additionally, the antibacterial properties of the volatile oil were assessed against four common pathogenic bacteria, namely Escherichia coli, Aerogenic bacterium, Listeria monocytogenes, and Bacillus subtilis). The findings exhibited potent antibacterial activity against Escherichia coli (MIC: 16 mg/mL) and Aerogenic bacterium (MIC: 1 mg/mL). However, the volatile oil exhibited weaker antibacterial activity against Listeria monocytogenes (MIC: 8 mg/mL) and Bacillus subtilis (MIC: 64 mg/mL).

The performance of most existing tomographic synthetic aperture radar (SAR) (TomoSAR) methods that reconstruct the scene pixel-by-pixel is degraded by speckle noise and low signal-to-noise ratio. To solve these problems, we propose a homogeneous region-based compressed sensing (HomoR-CS) method for SAR tomography. This method enhances the processing approach by transitioning from the traditional pixel-by-pixel processing to the joint processing based on multiple adjacent pixels in homogeneous regions. First, a similarity measure is designed to cluster pixels that have similar electromagnetic scattering intensities and three-dimensional (3-D) positions into homogeneous regions. Then, the homogeneous region-oriented TomoSAR signal model is proposed and the solution is given. Sparse approximation at the homogeneous region level is used to estimate the elevation for every pixel. The multiple adjacent pixels within the homogeneous region are jointly processed to determine the initial elevation centers, which are used as the prior information for the subsequent accurate elevation estimation of each pixel. Finally, the experimental analyses using both simulated and measured data validate the effectiveness of the HomoR-CS method. The results show that the HomoR-CS method reduces the outliers of 3-D reconstruction results and enhances the recovery of weak scattering targets.

Background: Our previous studies have shown that lipoxin A4 (LXA4) can serve as a potential biomarker for assessing the efficacy of exercise therapy in knee osteoarthritis (KOA), and fibroblast-like synoviocytes (FLSs) may play a crucial role in KOA pain as well as in the progression of the pathology. Objective: By analyzing the GSE29746 dataset and collecting synovial samples from patients with different Kellgren–Lawrence (KL) grades for validation, we focused on exploring the potential effect of LXA4 on ferroptosis in FLSs through the ESR2/LPAR3/Nrf2 axis to alleviate pain and pathological advancement in KOA. Methods: The association between FLSs ferroptosis and chondrocyte matrix degradation was explored by cell co-culture. We overexpressed and knocked down LPAR3 in vitro to explore its potential mechanism in FLSs. A rat model of monosodium iodoacetate (MIA)-induced KOA was constructed and intervened with moderate-intensity treadmill exercise and intraperitoneal injection of PHTPP to investigate the effects of the LXA4 intracellular receptor ESR2 on exercise therapy. Results: ESR2, LPAR3, and GPX4 levels in the synovium decreased with increasing KL grade. After LXA4 intervention in the co-culture system, GPX4, LPAR3, and ESR2 were upregulated in FLSs, collagen II was upregulated in chondrocytes, and MMP3 and ADAM9 were downregulated. LPAR3 overexpression upregulated the expression of GPX4, Nrf2, and SOD1 in FLSs, while downregulating the expression of MMP13 and MMP3; LPAR3 knockdown reversed these changes. Moderate-intensity platform training improved the behavioral manifestations of pain in KOA rats, whereas PHTPP treatment partially reversed the improvement in synovial and cartilage pathologies induced by platform training. Conclusion: LXA4 inhibited FLSs ferroptosis by activating the ESR2/LPAR3/Nrf2 axis, thereby alleviating the pain and pathological progression of KOA. This study brings a new target for the treatment of KOA and also leads to a deeper understanding of the potential mechanisms of exercise therapy for KOA.

BackgroundCataract surgery and laser peripheral iridotomy (LPI) are effective approaches for preventing primary angle closure diseases (PACDs), as well as acute primary angle closure (APAC). Due to the development of population screening and increases in cataract surgery rates, this study aimed to examine trends in the admission rates of PACD among the urban population in China.MethodsThis cross-sectional study examined patients who were admitted to a hospital for PACD, and who underwent cataract surgery or LPI operations. The data were obtained from the Yinzhou Regional Health Information Platform (YRHIP) from 2011 to 2021. The annual rates of PACD and APAC admissions, cataract surgery and LPI were analyzed, with the number of cases used as numerators and the annual resident population in Yinzhou district used as denominators.ResultsA total of 2,979 patients with PACD admissions, 1,023 patients with APAC admissions, 53,635 patients who underwent cataract surgery and 16,450 patients who underwent LPI were included. The number of annual admissions for PACD gradually increased from 22 cases (1.6/100000) in 2011 to 387 cases (30.8/100000) in 2016, after which it decreased to 232 cases (16.2/100000) in 2019 and then increased to 505 cases (30.6/100000) in 2021. The number of cataract surgeries gradually increased from 1728 (127.7/100000) in 2011 to 7002 (424.9/100000) in 2021. Similarly, the number of LPI gradually increased from 109 (8.0/100000) in 2011 to 3704 (224.8/100000) in 2021.ConclusionThe admission rates of PACD for the urban population in China have declined in recent years after a long increasing trend in the rates of cataract surgery and LPI. However, it increased rapidly during the COVID-19 epidemic. The national health database should be further utilized to investigate temporal trends in the prevalence of PACD.

BackgroundA phenomenon known as legacy effect was observed that poor glycemic control at early stage of patients with newly-diagnosed type 2 diabetes (T2D) increases the risk of subsequent cardiovascular diseases (CVD). Early use of some novel anti-hyperglycemic agents, such as sodium-glucose transport protein 2 inhibitors (SGLT-2i), may attenuate this effect, but the evidence is limited.MethodsTwo retrospective cohorts of newly diagnosed T2D patients from 2010–2023 were assembled using the Yinzhou Regional Health Care Database (YRHCD) with different definitions of the early exposure period - the 1-year exposure cohort and 2-year exposure cohort, which were comprised of subjects who had HbA1c measurement data within 1 year and 2 years after their T2D diagnosis, respectively. Using Cox proportional hazards models, we examined the association between high HbA1c level (HbA1c>7%) during the early exposure period and the risk of subsequent CVD. This analysis was performed in the overall cohort and three subpopulations with different treatments during the early exposure period, including patients initiating SGLT-2i or glucagon-like peptide-1 receptor agonists (GLP-1RA), patients using dipeptidyl peptidase-4 inhibitors (DPP-4i), and patients without using SGLT-2i, GLP-1RA, and DPP-4i. Besides, subgroup analyses were performed by stratifying patients into age 7% had higher risks of incident CVD, with a HR of 1.165 (95%CI, 1.056–1.285) and 1.143 (95%CI, 1.044–1.252) in 1-year and 2-year exposure period cohort. Compared to non-users, in patients initiating SGLT-2i/GLP-1RA within 1 or 2 years after T2D diagnosis, higher HbA1c level at baseline was not associated with CVD in both two cohorts. In subgroup analyses, results were generally consistent with the main analysis.ConclusionsPoor glycemic control in the early stage of T2D increased later CVD risk in Chinese adults with newly diagnosed T2D. Compared to non-users, this association was smaller and non-significant in patients receiving SGLT-2i/GLP-1RA during the early stage of T2D, indicating early use of these drugs may have the potential to mitigate legacy effects of hyperglycemia.

Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

Abstract The importance of uncommon/rare oncogenic drivers in non‐small cell lung cancer (NSCLC) was underscored during the 20th China Lung Cancer Summit. These drivers, while present in a significant proportion of NSCLC patients, remain a challenge for diagnosis and therapeutic targeting. In the never‐smokers/low smokers category with mutations such as EGFR and HER2, the efficacy of immune checkpoint inhibitors (ICIs) remains suboptimal, attributed to lower PD‐L1 expression and tumor mutation burden (TMB). However, heavy smokers, often with mutations like KRAS, may derive benefits from ICIs, as supported by trials like CheckMate‐057. With the complex landscape of these drivers and their clinical implications, the summit culminated in six pivotal consensus points, aiming to guide future research and clinical decisions. Despite the advancements, the detection, interpretation, and therapeutic strategies involving these drivers necessitate further exploration and standardization.

Abstract Aims To investigate the predictive value of baseline C-reactive protein (CRP) levels on the efficacy of chemotherapy plus immune checkpoint inhibitors (ICI) in patients with advanced lung squamous cell carcinoma (LSCC). Materials and methods In this retrospective multicenter study spanning from January 2016 to December 2020, advanced LSCC patients initially treated with chemotherapy or a combination of chemotherapy and ICI were categorized into normal and elevated CRP subgroups. The relationship between CRP levels and treatment outcomes was analyzed using multivariate Cox proportional hazards models and multivariate logistic regression, focusing primarily on the progression-free survival (PFS) endpoint, and secondarily on overall survival (OS) and objective response rate (ORR) endpoints. Survival curves were generated using the Kaplan-Meier method, with the log-rank test used for comparison between groups. Results Of the 245 patients evaluated, the 105 who received a combination of chemotherapy and ICI with elevated baseline CRP levels exhibited a significant reduction in PFS (median 6.5 months vs. 11.8 months, HR, 1.78; 95% CI: 1.12–2.81; p = 0.013) compared to those with normal CRP levels. Elevated CRP was identified as an independent risk factor for poor PFS through multivariate-adjusted analysis. However, among the 140 patients receiving chemotherapy alone, baseline CRP levels did not significantly influence PFS. Furthermore, within the combination therapy group, there was a notable decrease in the ORR (51% vs. 71%, p = 0.035), coupled with a significantly shorter OS (median 20.9 months vs. 31.5 months, HR, 2.24; 95% CI: 1.13–4.44; p = 0.033). Conclusion In patients with advanced LSCC, elevated baseline CRP levels were identified as an independent predictive factor for the efficacy of combination therapy with chemotherapy and ICI, but not in chemotherapy alone. This suggests that CRP may be a valuable biomarker for guiding treatment strategies.

Abstract The role of pyrotinib in the treatment of HER2-positive metastatic breast cancer (MBC) has been well-established. This multicenter, single-arm phase II trial (NCT03876587) aimed to assess the benefit of pyrotinib plus docetaxel as a first-line treatment for HER2-positive MBC. Women with HER2-positive MBC who had not undergone HER2 blockade or chemotherapy for metastatic disease were enrolled in the study and received daily oral pyrotinib 400 mg plus intravenous docetaxel 75 mg/m2 every 3 weeks. The primary endpoint was the objective response rate (ORR), secondary endpoints included progression-free survival (PFS), duration of response (DoR), clinical benefit rate (CBR), overall survival (OS) and safety. From June 2019 to June 2021, 79 patients were enrolled. The confirmed ORR was 79.7% (95% confidence interval [CI], 70.8-88.6), and the CBR was 87.3% (95%CI, 80.0-94.6) in the intention-to-treat population. The pre-specified primary endpoint was met. The median DoR was 15.9 months (interquartile range, 8.3-19.5); the median PFS was 16.0 months (95% CI, 11.2-20.8), and the median OS was not reached. The most common grade ≥3 treatment-related adverse events observed were leukopenia (29.1%), neutropenia (27.8%), and diarrhea (21.5%). This study demonstrates that pyrotinib plus docetaxel show an acceptable safety profile and promising antitumor activity as a first-line treatment option for patients with HER2-positive MBC.

Subacute ruminal acidosis (SARA) is a prevalent metabolic disorder in highly productive dairy cows that results in serious issues, including hoof lamellar injuries. This study aimed to investigate the efficacy of a carbonate buffer mixture (CBM) in preventing hoof lamella injury in dairy goats, a species also susceptible to SARA due to similar feeding practices over a 17-week period. Twenty-four healthy dairy goats were randomly assigned to three groups: control, SARA, and CBM groups. The control group received a standardized diet, whereas the SARA and CBM groups were subjected to a high-grain feeding regimen to induce SARA. The CBM group received a daily supplement of 10 g CBM mixed with their diet. Clinical assessments, including body temperature, rumen pH, inflammatory markers, matrix metalloproteinases (MMPs), and hoof lamellar injuries, were monitored throughout the study. The results showed that the CBM group maintained a more stable rumen pH and had lower levels of inflammatory markers than the SARA group did. The incidence of hoof lamellar injury was slightly lower in the CBM group. These findings suggest that long-term CBM supplementation may mitigate SARA-associated hoof lamella injury in dairy goats by regulating the rumen environment, fostering the growth of healthy bacterial communities, and by reducing the production of harmful metabolites. The use of CBM as a dietary supplement may have significant implications in improving the health, welfare, and productivity of dairy animals.

Sentinel-1A/B data are crucial for retrieving numerical information about surface phenomena and processes. Coregistration of terrain observation by progressive scans (TOPS) data is a critical step in its application. TOPS data must be fundamentally co-registered with an accuracy of 0.001 pixels. However, various decorrelation factors due to natural vegetation and seasonal effects affect the coregistration accuracy of TOPS data. This paper proposed an enhanced spectral diversity coregistration method for dual-polarimetric (PolESD) Sentinel-1A/B TOPS data. The PolESD method suppresses speckle noise based on a unified non-local framework in dual-pol Synthetic Aperture Radar (SAR), and extracts the phase of the optimal polarization channel from the denoised polarimetric interferometric coherency matrix. Compared with the traditional ESD method developed for single-polarization data, the PolESD method can obtain more accurate coherence and phase and get more pixels for azimuth-offset estimation. In bare areas covered with low vegetation, the number of pixels selected by PolESD is more than the Boxcar method. It can also correct misregistration more effectively and eliminate phase jumps in the burst edge. Therefore, PolESD will help improve the application of TOPS data in low-coherence scenarios.

Abstract Lots of real-world optimization problems are inherently constrained multi-objective optimization problems (CMOPs), but the existing constrained multi-objective optimization evolutionary algorithms (CMOEAs) often fail to balance convergence and diversity effectively. Therefore, a novel constrained multi-objective optimization evolutionary algorithm based on three-stage multi-population coevolution (CMOEA-TMC) for complex CMOPs is proposed. CMOEA-TMC contains two populations, called mainPop and helpPop, which evolve with and without consideration of constraints, respectively. The proposed algorithm divides the search process into three stages. In the first stage, fast convergence is achieved by transforming the original multi-objective problems into multiple single-objective problems. Coarse-grained parallel evolution of subpopulations in mainPop and guidance information provided by helpPop can facilitate mainPop to quickly approach the Pareto front. In the second stage, the objective function of mainPop changes to the original problem. Coevolution of mainPop and helpPop by sharing offsprings can produce solutions with better diversity. In the third stage, the mining of the global optimal solutions is performed, discarding helpPop to save computational resources. For CMOEA-TMC, the combination of parallel evolution, coevolution, and staging strategy makes it easier for mainPop to converge and maintain good diversity. Experimental results on 33 benchmark CMOPs and a real-world boiler combustion optimization case show that CMOEA-TMC is more competitive than the other five advanced CMOEAs.

Abstract Purpose The significance of detecting human herpesvirus 7 (HHV-7) in the lower respiratory tract of patients with severe pneumonia is unclear. This study aims to evaluate the clinical characteristics and prognosis of detecting HHV-7 in the lower respiratory tract of patients with severe pneumonia. Methods Patients with severe pneumonia requiring invasive mechanical ventilation and underwent commercial metagenomic next-generation sequencing (mNGS) testing of bronchoalveolar lavage fluid from January 2019 to March 2023 were enrolled in 12 medical centers. Clinical data of patients were collected retrospectively, and propensity score matching was used for subgroup analysis and mortality assessment. Results In a total number of 721 patients, 45 cases (6.24%) were identified with HHV-7 positive in lower respiratory tract. HHV-7 positive patients were younger (59.2 vs 64.4, p = 0.032) and had a higher rate of co-detection with Cytomegalovirus (42.2% vs 20.7%, p = 0.001) and Epstein–Barr virus (35.6% vs 18.2%, p = 0.008). After propensity score matching for gender, age, SOFA score at ICU admission, and days from ICU admission to mNGS assay, there was no statistically significant difference in the 28-day mortality rate between HHV-7 positive and negative patients (46.2% vs 36.0%, p = 0.395). Multivariate Cox regression analysis adjusting for gender, age, and SOFA score showed that HHV-7 positive was not an independent risk factor for 28-day mortality (HR 1.783, 95%CI 0.936–3.400, p = 0.079). Conclusion HHV-7 was detected in the lungs of 6.24% of patients with severe pneumonia. The presence of HHV-7 in patients with severe pneumonia requiring invasive mechanical ventilation is associated with a younger age and co-detected of Cytomegalovirus and Epstein–Barr virus. While HHV-7 positivity was not found to be an independent risk factor for mortality in this cohort, this result may have been influenced by the relatively small sample size of the study.

The improvement of corrosion resistance for sintered Nd-Fe-B magnets is usually focused on the modification of grain boundary phase. The main phase is similarly a key point to enhance corrosion resistance. In this work, a novel sintered Nd-Fe-B magnet is designed with the addition of Ni and Cr. This kind of sintered Nd-Ni-Fe-Cr-B magnet maintains a typical 2:14:1 tetragonal phase, and the metallurgical behavior of Ni and Cr is characterized by the distribution of Ni in the grain boundary and Cr in the main phase. Accelerated corrosion and electrochemical corrosion tests were conducted to compare the corrosion resistance of traditional sintered Nd-Fe-B magnet and Nd-Ni-Fe-Cr-B magnet. Results show that sintered Nd-Ni-Fe-Cr-B magnet exhibits superior corrosion resistance. It is found that the corrosion resistance of the grain boundary phase and the main phase is simultaneously increased. Moreover, the reduced potential difference between the grain boundary phase and the main phase further enhances the corrosion resistance of sintered Nd-Ni-Fe-Cr-B magnet. This work could provide an insight into the research aimed at improving the corrosion resistance of uncoated sintered Nd-Fe-B magnets.

IntroductionSmall cell lung cancer (SCLC) transformation serves as a significant mechanism of resistance to tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. To address this clinical challenge, we conducted a retrospective analysis at Zhejiang University School of Medicine, the First Affiliated Hospital, focusing on patients with EGFR sensitizing mutations.MethodsA total of 1012 cases were included in this retrospective analysis. The cohort primarily consisted of patients with EGFR sensitizing mutations. Biopsy-confirmed small cell transformation was observed in seven patients, accounting for 0.7% of the cases. All patients in this subset were initially diagnosed with stage IV adenocarcinoma (ADC), with four cases classified as poorly differentiated and three as moderately to poorly differentiated ADC. EGFR exon 19 deletions were identified in five of these cases. Next-generation sequencing (NGS) was performed on seven cases, revealing mutations in the tumor protein p53 (TP53) gene in four cases and loss of the retinoblastoma1 (RB1) gene in three cases.ResultsThe median duration from the initial diagnosis to small cell transformation was 35.9 months (interquartile range: 12.1–84 months). Following small cell transformation during EGFR inhibition, all patients received etoposide/platinum-based treatment, leading to a median progression-free survival (PFS) of 4.7 months (interquartile range: 2.7–10.1 months). Notably, most patients in this series had poorly differentiated adenocarcinomas at the outset. TP53 mutations and RB1 loss were common genetic alterations observed in patients with small cell transformation in this cohort.DiscussionThe findings underscore the clinical significance of SCLC transformation as a resistance mechanism to EGFR TKIs in NSCLC with EGFR mutations. The observed genetic alterations, including TP53 mutations and RB1 loss, suggest potential associations with the transformation process and warrant further investigation. Understanding the genetic landscape and clinical outcomes in patients experiencing small cell transformation can contribute to improved strategies for managing resistance in EGFR-mutant NSCLC.

Shanghai Pudong International Airport (PDIA), with its east side built along the coast with weak geological conditions, is prone to uneven foundation settlement due to the consolidation and compression of soil and erosion of coastal tides, affecting the safe operation of the airport. Therefore, it is crucial to conduct dynamic subsidence monitoring within the airport, especially in the runway area. 29 scenes of ascending track Sentinel-1A radar images from August 2016 to June 2018 are selected to perform surface deformation inversion based on PS-InSAR and improved SBAS-InSAR for PDIA and its around coastal area. Through cross-validation, the reliability of the time-series InSAR technique for dynamic monitoring of surface deformation of coastal zone infrastructures is confirmed. The results show severely uneven settlement. By combining the monitoring results with the local geological and hydrological dataset, the driving factors of differential deformation of the infrastructures are analyzed, including stratigraphic geological conditions, ground loadings, foundation treatment methods, water erosion, and groundwater level changes. Finally, the time-series deformation characteristics and the causes of PDIA's runway are emphasized based on the PS deformation results. This case provides a reference for the safety management of critical infrastructure in coastal areas using advanced InSAR technique.

Abstract Stage III non‐small cell lung cancer (NSCLC) encompasses a group of diseases with high heterogeneity. Such patients should actively receive comprehensive treatments. It is imperative for all stage III NSCLC patients to receive consultation with a multiple disciplinary team, which allows the development of a proposal for clinical diagnosis and treatment. In this consensus, stage III NSCLC is divided into two types (operable and inoperable) according to different clinical conditions. Resectable NSCLC is further subdivided into two conditions (with or without driver genes). For each clinical scenario, this consensus emphasizes that the foundation of any medical decisions regarding the optimal diagnostic or therapy procedure is scientific evidence from clinical research. Finally, based on the level of evidence and strength of recommendations, this consensus provides recommendations for the management of stage III NSCLC from six perspectives. The objective of this consensus is to help clinicians choose the best treatment and promote the standardization of stage III NSCLC diagnosis and treatment in China.

Abstract Background Type 2 diabetes mellitus (T2DM) and dementia cause heavy health burden in mainland China, where few studies have investigated the association between glucose‐lowering agents and dementia risk. We aimed to assess the association between use of thiazolidinediones (TZDs) and dementia incidence in a mainland Chinese population with T2DM. Methods A retrospective cohort of T2DM patients who were new users of TZDs or alpha glucosidase inhibitors (AGIs) was assembled using the Yinzhou Regional Health Care Database. A Cox model with inverse probability of treatment weighting (IPTW) for controlling potential founding was applied to estimate the hazard ratio (HR) of the association between use of TZDs and dementia risk. Results A total of 49 823 new users of AGIs and 12 752 new users of TZDs were included in the final cohort. In the primary analysis, the incidence of dementia was 195.7 and 78.2 per 100 000 person‐years in users of AGIs and TZDs respectively. TZD use was associated with a reduced risk of incident dementia after adjusting for potential confounding using IPTW, with a HR of 0.51 (95% CI, 0.38–0.67). The results in various subgroup analyses and sensitivity analyses were consistent with the findings of the primary analysis. Conclusions Use of TZDs is associated with a decreased risk of dementia incidence in a mainland Chinese population with T2DM.

Abstract Background This study investigated the efficacy of the integrated blood purification mode of early haemoperfusion (HP) combined with continuous venovenous haemodiafiltration (CVVHDF) in children with severe viral encephalitis, and evaluated the correlation of cerebrospinal fluid (CSF) neopterin (NPT) levels with prognosis. Methods The records of children with viral encephalitis who received blood purification treatment in the authors’ hospital from September 2019 to February 2022 were retrospectively analysed. According to the blood purification treatment mode, they were divided into the experimental group (HP + CVVHDF, 18 cases), control group A (CVVHDF only, 14 cases), and control group B (16 children with mild viral encephalitis who did not receive blood purification treatment). The correlation between the clinical features, severity of the disease and the extent of lesions on brain magnetic resonance imaging (MRI) and the CSF NPT levels was analysed. Results The experimental group and control group A were comparable with respect to age, gender and hospital course (P > 0.05). There was no significant difference in speech and swallowing functions between the two groups after treatment (P > 0.05) and no significant difference in 7 and 14-day mortality (P > 0.05). The CSF NPT levels in the experimental group before treatment were significantly higher compared with control group B (P

The ability to selectively emit in specific spectral bands, known as spectral selective emission, is highly valuable in thermal photovoltaic systems, infrared stealth, radiation heat dissipation, and other fields. This paper presents a planarized molybdenum/zinc sulfide (Mo/ZnS) multilayer film design to achieve infrared stealth under high temperatures. By utilizing the distinctive radiation characteristics of an ultra-thin Mo layer and impedance matching, selective emission in the infrared band can be achieved. The fabricated multilayer films have low emissivity in the atmospheric window (ε(3–5μm) = 0.19; ε(8–14μm) = 0.29), but high emissivity in the non-atmospheric window (ε(5–8μm) = 0.7). In addition to ensuring infrared stealth performance, the films can also withstand high temperatures up to 723K with good high-temperature resistance. Moreover, the proposed design has several advantages, including structural simplicity, ductility, and ease of mass production. This work could bring added convenience to many applications, including infrared stealth, in the future.

Abstract Background Protein arginine methyltransferase 5 (PRMT5) is upregulated in multiple tumors and plays a pivotal role in cancer cell proliferation. However, the role of PRMT5 in colorectal cancer remains poorly understood. Methods We detected the expression level of PRMT5 and glycolytic enzymes using online databases and colorectal cancer cell lines by immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. And MTT and colony formation assays were conducted to investigate cell proliferation. Then, we evaluated ECAR and OCR levels using a biological energy analyzer to investigate the energy status of colorectal cancer, and the transcriptional regulation was detected by dual luciferase reporter assay and ChIP assay. Finally, the efficacy of combined treatment of tadalafil and 5-FU was verified. Results PRMT5 was highly expressed in colorectal cancer tissues compared with their normal counterparts and correlated with poor prognosis in CRC patients. Then, we demonstrated that PRMT5 knockdown or loss of function attenuated the viability of CRC cells, while overexpression of PRMT5 promoted cell proliferation. Mechanistically, PRMT5 enhanced glycolysis through transcriptionally activating LDHA expression. In addition, the PRMT5 inhibitor, tadalafil, rendered CRC cells sensitive to antitumor agent 5-FU in vitro and in vivo. Conclusions Our data indicates that PRMT5 promoted colorectal cancer proliferation partially through activating glycolysis and may be a potential target for colorectal cancer therapy.

Abstract Background Cervical cancer is one of the most common cancers in women and could be prevented by human papilloma virus (HPV) vaccination. Cervarix, the first available HPV vaccine, has been widely administrated to Chinese women, while little was known about its effect on the prevention and control for HPV related diseases in China. The study aims to assess the impact of Cervarix on HPV infection and cervical related diseases in real world. Methods This is a prospective, multi-age birth cohort study to investigate the incidence and continuous status of HPV infection, and relevant cervical diseases by exposure status (with Cervarix vaccination history or without any HPV vaccination history). It is planned to recruit 12,118 eligible women at age of 9 to 45 years from vaccination clinics or hospital outpatient clinics, and then follow up them for three years. The standard questionnaire will be used to collect information such as demographic characteristics, menstruation and obstetrical histories, history of sexual behavior, personal behavior history, history of disease and pathogen infection, medication history, and family history at baseline. After three years, the changes of these behaviors will be investigated again, and other related health status information will be retrieved from the electronic health records during the follow-up period. If available physically and legally, the cervical cancer screening will be performed, including type-specific HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) testing and contingent thinprep cytologic test (TCT) and colposcopy. The free cervical cancer screening will be captured and uploaded timely to the Yinzhou Regional Health Information Platform (YRHIP); therefore, the long-term outcomes of participants will be monitored. Discussion This prospective cohort study will assess the impact of HPV vaccine on HPV infection and related cervical diseases in women aged 9–45 years, which makes up for the lack of evidence in Chinese women. The results of this study will provide support for understanding the impact of HPV vaccination in China, and make a contribution to increasing HPV vaccination and cervical cancer screening coverage in China. Trial registration This study has been retrospectively registered on clinicaltrials.gov (NCT05341284) on April 22, 2022.

Abstract The health burden of Parkinson’s disease (PD) and diabetes increases rapidly in China. However, no population-based study of the association between glucose lowering agents and PD incidence has been conducted in mainland Chinese population. Preclinical studies indicate that thiazolidinediones (TZDs) have neuroprotective effects against PD through stimulating peroxisome proliferator-activated receptor gamma. Nevertheless, debate remains in human studies. We assembled a retrospective cohort of type 2 diabetes mellitus (T2DM) patients who were new users of TZDs or alpha glucosidase inhibitors (AGIs) using the Yinzhou Regional Health Care Database. A Cox model with inverse probability of treatment weighting (IPTW) was applied to estimate the hazard ratio (HR) of PD incidence associated with the use of TZDs compared with AGIs. The final cohort included 12,704 new users of TZDs and 49,696 new users of AGIs. The incidence of PD was 135 per 100,000 person-years in TZD users and 203 per 100,000 person-years in the AGI group. An inverse association between use of TZDs and incidence of PD, with a HR of 0.74 (95% confidence interval, 0.59–0.92), was observed after adjusting for potential confounding using IPTW. The results of various subgroup analyses and sensitivity analyses were consistent with the findings of the primary analysis. Our results indicated that the use of TZD is associated with a decreased risk of PD incidence in a mainland Chinese population with T2DM. Given the heavy disease burden of PD and diabetes in China, these findings could provide some evidence for developing effective prevention and control measures to reduce the future incidence of PD in China.

IntroductionGut microbiota reportedly play a critical role in some autoimmune diseases by maintaining immune homeostasis. Only a few studies have examined the correlation between gut microbiota and the onset of primary immune thrombocytopenia (ITP), especially in children. The purpose of this study was to investigate changes in the composition and diversity of the fecal microbiota of children with ITP, as well as the correlation between such microbiota and the onset of ITP.MethodsTwenty-five children newly diagnosed with ITP and 16 healthy volunteers (controls) were selected for the study. Fresh stool samples were collected to identify changes in the composition and diversity of gut microbiota as well as for potential correlation analysis.ResultsIn ITP patients, the phyla that were most frequently encountered were Firmicutes (54.3%), followed by Actinobacteria (19.79%), Bacteriodetes (16.06%), and Proteobacteria (8.75%). The phyla that were predominantly found in the controls were, Firmicutes (45.84%), Actinobacteria (40.15%), Bacteriodetes (3.42%), and Proteobacteria (10.23%). Compared with those of the controls, the proportions of Firmicutes and Bacteriodetes in the gut microbiota of ITP patients were increased while the proportions of Actinobacteria and Proteobacteria were decreased. Furthermore, gut microbiota in ITP patients varied by age group, showed specific changes in diversity, and were correlated with antiplatelet antibodies. IgG levels were significantly positively correlated with Bacteroides (P

Abstract Purpose Cognitive impairment is a critical complication of acute respiratory distress syndrome (ARDS). However, effective interventions are lacking. Growing evidence demonstrates that c‐Jun N‐terminal kinase (JNK)‐mediated neuroinflammation is involved in the development of ARDS. Therefore, we hypothesized that the JNK pathway is involved in ARDS‐induced cognitive impairment. Methods An in vivo rat model of ARDS was established by treating it with lipopolysaccharide. The cognitive function was assessed by behavioral tests. The levels of pro‐inflammatory cytokines, JNK and NOD‐, LRR‐, and pyrin domain‐containing protein 3 (NLRP3) were analyzed by enzyme‐linked immunosorbent assay, western blot, or immunohistochemical analysis. Results We found that JNK inhibitor 8 (JNK‐IN‐8) alleviated cognitive impairment, neuroinflammation, and NLRP3 inflammasome activation in the ARDS rat model. Additionally, an in vivo study showed that the protective effect of JNK‐IN‐8 on cognitive impairment was blocked by nigericin, an NLRP3 activator. Conclusions Our data suggest that JNK‐IN‐8 treatment improves ARDS‐induced cognitive impairment by inhibiting the JNK/nuclear factor‐κB‐mediated NLRP3 inflammasome.

Quasi-continuous wave radar is an attempt to give consideration to the performance of pulse and continuous wave radar signals. However, it also has the shortcomings of both. This paper aims to add a new quasi-continuous-wave coding method to the spaceborne synthetic aperture radar (SAR) system. The technology of improving spaceborne SAR imaging performance by coding quasi-continuous-wave pulses is studied, and some shortcomings of this algorithm are improved. Firstly, the application of quasi-continuous-wave radar in the SAR system is studied, and the coding and reconstruction scheme is provided so that this technology can be successfully applied in spaceborne SAR. Secondly, the effects of different quasi-continuous-wave coding methods on SAR imaging performance are evaluated, including signal-to-noise ratio, resolution, and integration time. Then, several coding schemes are given, and the characteristic changes of the signal after quasi-continuous-wave coding are analyzed. The transmit–receive conversion loss function and azimuth Doppler ambiguity function of the design scheme are analyzed, which proves the advantages of the scheme. Finally, we design the hardware implementation scheme and carry out the practical test.

Abstract Pancreatic cancer (PC) is a highly malignant solid tumor with insidious onset and easy early metastasis. Despite tremendous efforts devoted to research in this field, the mechanisms underlying PC tumorigenesis and progression remain unclear. Additionally, robust biomarkers and satisfactory therapeutic strategies for clinical use in PC patients are still lacking. Circular RNAs (circRNAs) are a new type of non-coding RNA originating from precursor messenger RNAs, with a covalent continuous closed-loop structure, strong stability and high specificity. Accumulating evidence suggests that circRNAs may participate in PC development and progression. Abnormal expression of circRNAs in PC is considered a vital factor that affects tumor cell proliferation, migration, invasion, apoptosis, angiogenesis and drug resistance. In this review of relevant articles published in recent years, we describe the basic knowledge concerning circRNAs, including their classification, biogenesis, functions and research approaches. Moreover, the biological roles and clinical significance of circRNAs related to PC are discussed. Finally, we note the questions remaining from recent studies and anticipate that further investigations will address these gaps in knowledge in this field. In conclusion, we expect to provide insights into circRNAs as potential targets for specific PC diagnosis and treatment in the future.

Abstract Background circular RNAs (circRNAs) have been reported to play crucial roles in the biology of different cancers. However, little is known about the function of circSTX6 (hsa_circ_0007905) in pancreatic ductal adenocarcinoma (PDAC). Methods circSTX6, a circRNA containing exons 4, 5, 6 and 7 of the STX6 gene, was identified by RNA sequencing and detected by quantitative reverse transcription PCR (qRT–PCR). The biological function of circSTX6 was assessed in vitro and in vivo. The relationship between circSTX6 and miR-449b-5p was confirmed by biotin-coupled circRNA capture, fluorescence in situ hybridization (FISH) and luciferase reporter assays. The interaction of circSTX6 with Cullin 2 (CUL2) was verified by RNA–protein RNA pull-down, RNA immunoprecipitation (RIP) and western blotting assays. Results circSTX6 was frequently upregulated in PDAC tissues, and circSTX6 overexpression promoted tumor proliferation and metastasis both in vitro and in vivo. Furthermore, circSTX6 expression was associated with tumor differentiation and N stage. Mechanistically, circSTX6 regulated the expression of non-muscle myosin heavy chain 9 (MYH9) by sponging miR-449b-5p. Moreover, circSTX6 was confirmed to participate in the ubiquitin-dependent degradation of hypoxia-inducible factor 1-alpha (HIF1A) by interacting with CUL2 and subsequently accelerating the transcription of MYH9. Conclusions Our findings indicate that circSTX6 facilitates proliferation and metastasis of PDAC cells by regulating the expression of MYH9 through the circSTX6/miR-449b-5p axis and circSTX6/CUL2/HIF1A signaling pathway. Therefore, circSTX6 could serve as a potential therapeutic target for the treatment of PDAC.

Asymmetric n/p conductivity is a fundamental difficulty in wide bandgap semiconductors. Here the authors demonstrate a concept of orbital level engineering through sacrificial impurity coupling to achieve n-type conductivity (ne ~1016 cm-3) in hexagonal BN.

Osteoarthritis (OA) is a degenerative disease that is difficult to cure owing to its complicated pathogenesis. Exercise therapy has been endorsed as a primary treatment option. However, it remains controversial how exercise intensity regulates OA progression. Here, a declining propensity for TGF-β1 was predicted via bioinformatics analysis of microarray GSE57218 and validated in cartilage samples obtained from arthroplasty. Based on this, cyclic tensile strain or TGF-β1 intervention was performed on human OA chondrocytes, and we found that moderate-intensity mechanical loads protected chondrocytes against pyroptosis. During this process, the elevation of TGF-β1 is mechanically stimuli-dependent and exerts an inhibitory effect on chondrocyte pyroptosis. Moreover, we elucidated that TGF-β1 activated Smad2/3 and inhibited the NF-κB signaling pathway to suppress chondrocyte pyroptosis. Furthermore, we established a rat knee OA model by intra-articular injection of monosodium iodoacetate and performed treadmill exercises of different intensities. Similar to the in vitro results, we demonstrated that moderate-intensity treadmill exercise had an outstanding chondroprotective effect. An inappropriate intensity of mechanical stimulation may aggravate OA both in vivo and in vitro. Overall, our findings demonstrated that activation of the TGF-β1/Smad2/Smad3 axis and inhibition of NF-κB coordinately inhibit chondrocyte pyroptosis under mechanical loads. This study sheds light on the future development of safe and effective exercise therapies for OA.

Abstract Background The Yinzhou Center for Disease Prevention and Control (CDC) in China implemented an integrated health big data platform (IHBDP) that pooled health data from healthcare providers to combat the spread of infectious diseases, such as dengue fever and pulmonary tuberculosis (TB), and to identify gaps in vaccination uptake among migrant children. Methods IHBDP is composed of medical data from clinics, electronic health records, residents’ annual medical checkup and immunization records, as well as administrative data, such as student registries. We programmed IHBDP to automatically scan for and detect dengue and TB carriers, as well as identify migrant children with incomplete immunization according to a comprehensive set of screening criteria developed by public health and medical experts. We compared the effectiveness of the big data screening with existing traditional screening methods. Results IHBDP successfully identified six cases of dengue out of a pool of 3972 suspected cases, whereas the traditional method only identified four cases (which were also detected by IHBDP). For TB, IHBDP identified 288 suspected cases from a total of 43,521 university students, in which three cases were eventually confirmed to be TB carriers through subsequent follow up CT or T-SPOT.TB tests. As for immunization screenings, IHBDP identified 240 migrant children with incomplete immunization, but the traditional door-to-door screening method only identified 20 ones. Conclusions Our study has demonstrated the effectiveness of using IHBDP to detect both acute and chronic infectious disease patients and identify children with incomplete immunization as compared to traditional screening methods.

We investigated the association of long-term exposure to atmospheric PM2.5 with non-accidental and cause-specific mortality in Yinzhou, China. From July 2015 to January 2018, a total of 29,564 individuals aged ≥ 40 years in Yinzhou were recruited for a prospective cohort study. We used the Cox proportional-hazards model to analyze the relationship of the 2-year average concentration of PM2.5 prior to the baseline with non-accidental and cause-specific mortality. The median PM2.5 concentration was 36.51 μg/m3 (range: 25.57–45.40 μg/m3). In model 4, the hazard ratios per 10 μg/m3 increment in PM2.5 were 1.25 (95%CI: 1.04–1.50) for non-accidental mortality and 1.38 (95%CI:1.02–1.86) for cardiovascular disease mortality. We observed no associations between PM2.5 and deaths from respiratory disease or cancer. In the subgroup analysis, interactions were observed between PM2.5 and age, as well as preventive measures on hazy days. The observed association between long-term exposure to atmospheric PM2.5 at a relatively moderate concentration and the risk of non-accidental and cardiovascular disease mortality among middle-aged and elderly Chinese adults could provide evidence for government decision-makers to revise environmental policies towards a more stringent standard.

In this paper, a novel inverse model is designed for multivariable disturbance observer-based (MDOB) control system. A new interaction measure, generalized relative input disturbance gain (GRIDG), is proposed to quantify the disturbance rejection capabilities of different inverse model structures. Consequently, an inverse model with partially coupled structure can be determined for better disturbance rejection performance. Besides, by defining a relative input disturbance gain array (RIDGA), the values of GRIDG under different input-output pairings and structures can be derived in an intuitive manner, which greatly facilitates the structure selection of the inverse model. And then, to overcome the difficulty of implementing the partially coupled inverse model, a V canonical structure is used without introducing model approximation. It also has the advantage of simple calculation and being easy to generalize to high-dimensional systems. Finally, simulation examples of several multivariable industrial processes are given to illustrate the design procedure and demonstrate the effectiveness of the proposed strategy.

In this paper, a new pathway was proposed to assess the germplasm genetic variation by multidimensional traits of wheat seeds generated from digital images. A machine vision platform was first established to reconstruct wheat germplasm 3D model from omnidirectional image sequences of wheat seeds. Then, multidimensional traits were conducted from the wheat germplasm 3D model, including seed length, width, thickness, surface area, volume, maximum projection area, roundness, and 2 new defined traits called cardioid-derived area and the index of adjustment (J index). To assess genetic variation of wheat germplasm, phenotypic coefficients of variation (PCVs), analysis of variance (ANOVA), clustering, and the defined genetic variation factor (GVF) were calculated using the extracted morphological traits of 15 wheat accessions comprising 13 offspring and 2 parents. The measurement accuracy of 3D reconstruction model is demonstrated by the correlation coefficient (R) and root mean square errors (RMSEs). Results of PCVs among all the traits show importance of multidimensional traits, as seed volume (22.4%), cardioid-derived area (16.97%), and maximum projection area (14.67%). ANOVA shows a highly significance difference among all accessions. The results of GVF innovatively reflect the connection between genotypic variance and phenotypic traits from parents to offspring. Our results confirmed that extracting multidimensional traits from digital images is a promising high-throughput and cost-efficient pathway that can be included as a valuable approach in genetic variation assessment, and it can provide useful information for genetic improvement, preservation, and evaluation of wheat germplasm.

Background: Epidemiological studies have reported an association between traffic-related pollution with risk of metabolic syndrome (MetS). However, evidence from prospective studies on the association of walkability and nitrogen dioxide (NO2) with MetS is still scarce. We, therefore, aimed to evaluate the association of long-term exposure to NO2 and walkability with hazards of incident MetS. Methods: A total of 17,965 participants without MetS diagnosed within one year at baseline were included in our study from a population-based prospective cohort in Yinzhou District, Ningbo, Zhejiang Province, China. Participants were followed up by the regional Health Information System (HIS) until December 15, 2021. MetS was defined based on the criteria of Chinese Diabetes Society (CDS2004). We used walkscore tools, calculating with amenity categories and decay functions, and spatial–temporal land-use regression (LUR) models to estimate walkability and NO2 concentrations. We used Cox proportional hazards regression models to examine the association of walkability and NO2 with hazards of MetS incidence reporting with hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Overall, we followed up 77,303 person-years and identified 4040 incident cases of MetS in the entire cohort. Higher walkability was inversely associated with incident MetS (HR = 0.94, 95 % CI: 0.91–0.99), whereas NO2 was positively associated with MetS incidence (HR = 1.07, 95 %CI: 1.00–1.15) per interquartile range increment in two-exposure models. Furthermore, we found a significant multiplicative interaction between walkability and NO2. Stronger associations were observed for NO2 and incident MetS among men, smokers, drinkers and participants who aged

Prolonged drought stress caused by global warming poses a tremendous challenge to silage production of maize. Drought during maize growth and development resulted in altered micro-environment for silage fermentation. How fermentation of silage maize responds to moisture scales remains uncharted territory. In this research, Maize water control trials were conducted and the silage quality and microbial community of drought-affected maize were determined. The results showed that drought stress significantly reduced the dry matter but increased root-to-shoot ratio, soluble sugar and malonaldehyde content in maize. Before fermentation, the crude protein, crude ash and acid detergent fiber contents were significantly increased but the ether extract content was decreased under drought. The crude protein and acid detergent fiber were significantly decreased in the drought affected group after fermentation. Furthermore, water stress at maize maturity stage greatly reduced the number of total bacteria in silage fermentation but increased the proportion of the lactobacillus and lactic acid content of silage. Drought stress alters the microbial ecosystem of the fermentation process and reconstitutes the diversity of the bacterial community and its metabolites. This study provides a theoretical basis for the study of changes in silage fermentation as affected by abiotic stresses.

Abstract Enkurin, TRPC Channel Interacting Protein (ENKUR) was shown as a suppressor in some tumors. However, the biological role of ENKUR on gastric cancer (GC) and its related molecular mechanisms is not clear. Here, we first observed that ENKUR significantly inhibited cell migration, invasion, and metastasis in GC. The molecular basis showed β‐catenin‐mediated epithelial‐mesenchymal transition (EMT) signaling was inactivated in ENKUR‐overexpressing GC cells. In addition, ENKUR knockdown markedly restored cell migration and invasion. Subsequently, ENKUR bound to MYH9 and decreased its protein expression by recruiting E3 ubiquitin ligase F‐Box And WD Repeat Domain Containing 7 (FBXW7) to form an ubiquitinated degradation complex. The downregulated Myosin Heavy Chain 9 (MYH9) protein weakened the recruitment of the deubiquitinase USP2 and thus promoted the degradation of β‐catenin protein, which finally suppressed EMT signaling. Finally, the oncogenic transcription factor c‐Jun bound to ENKUR promoter and reduced its expression in GC. In clinical samples, decreased ENKUR expression promoted the unfavorable prognosis of GC. Our data proved the vital role of ENKUR on suppressing cell migration, invasion, and metastasis and demonstrated its potential as a therapeutic target for GC.