Search

Recent studies have identified that metabolic reprogramming in lung adenocarcinoma cells, particularly lactate metabolism disorders, plays a crucial role in tumor development and immune therapy response. The accumulation of lactic acid not only provides energy support for the proliferation of tumor cells but also affects the function of immune cells by changing the tumor microenvironment, thereby promoting immune escape. Immunotherapy, especially the application of immune checkpoint inhibitors, has become an important strategy for treating lung adenocarcinoma. However, lactate metabolism disorders might affect the efficacy of immunotherapy, leading to resistance in some patients. Therefore, a thorough understanding of the mechanisms of lactic acid metabolism in lung adenocarcinoma and its impact on the response to immunotherapy is essential for developing new therapeutic strategies and improving the efficacy of immunotherapy. This review summarizes the role of lactate metabolism disorders in the development and immunotherapy of lung adenocarcinoma, discusses the potential role of lactic acid metabolism-related genes and pathways in lung adenocarcinoma, and explores the progress in therapeutic strategies targeting lactic acid metabolism regulation. This work aims to provide new insights for the treatment of lung adenocarcinoma.

Abstract Background To investigate the prognostic differences following the achievement of a pathological complete response (pCR) through neoadjuvant chemotherapy across different molecular subtypes of breast invasive ductal carcinoma. Methods Data from the Surveillance, Epidemiology, and End Results (SEER) were identified for patients undergoing neoadjuvant chemotherapy who achieved pathological complete response for invasive ductal carcinoma of the breast between 2010 and 2019.Comparing the clinicopathological characteristics of patients across different molecular subtypes. Univariate and Cox multivariate analyses were utilized to identify independent predictors of overall survival (OS) and cancer-specific survival (CSS). The Kaplan–Meier method is used to compare OS and CSS among different molecular subtypes. After propensity score matching, subgroup analysis results were presented through forest plots. Results This study included 9,380 patients diagnosed with invasive ductal carcinoma, who were categorized into four molecular subtypes: 2,721 (29.01%) HR + /HER-2 + , 1,661 (17.71%) HR + /HER2-, 2,082 (22.20%) HR-/HER2 + , and 2,916 (31.08%) HR-/HER-2-. HR + /HER-2- subgroup exhibited a significantly higher proportion of patients under 50 years old than the other subtype groups (54.67% vs 40.2%, 50.35% and 51.82%, p

Objective: Chronic inflammation is a common feature in diabetes, especially when blood sugar levels are poorlycontrolled. This chronic low-grade inflammation can affect various organs, including the kidneys. Podocytedamage play a key role in the development of diabetic nephropathy (DN). The aim of the study was to evaluatethe nephroprotective effect of Boeravinone B (BB) against streptozotocin (STZ) induced DN in rats and explore theunderlying mechanism.Materials and Methods: In this experimental study, the rats received intraperitoneal injections of STZ (60 mg/kg) toinduce DN. Various doses of BB (2.5, 5, and 7.5 mg/kg) were administered orally. Glucose levels, body weights, andorgan weights (hepatic and renal) were assessed. Renal, histomorphological, antioxidant, hepatic, and cytokine levelswere determined, as were the mRNA expression levels of JAK2 and STAT3. At end of the experimental study, the ratswere sacrificed and their renal tissues were removed for histopathological assessment.Results: BB treatment decreased glucose levels and increased body weights. This treatment suppressed hepaticweights, increased renal tissue weights, and also decreased renal parameters like uric acid, urea, bilirubin, creatinine(Cr) and, albumin. There was a decrease (P

Abstract Background Though tamoxifen achieves success in treating estrogen receptor α (ERα)-positive breast cancer, the followed development of tamoxifen resistance is a common challenge in clinic. Signals downstream of prolactin receptor (PRLR) could synergize with ERα in breast cancer progression. However, the potential effect of targeting PRL-PRLR axis combined with tamoxifen has not been thoroughly investigated. Methods High-throughput RNA-seq data obtained from TCGA, Metabric and GEO datasets were analyzed to explore PRLR expression in breast cancer cell and the association of PRLR expression with tamoxifen treatment. Exogenous or PRL overexpression cell models were employed to investigate the role of activated PRLR pathway in mediating tamoxifen insensitivity. Immunotoxin targeting PRLR (N8-PE24) was constructed with splicing-intein technique, and the efficacy of N8-PE24 against breast cancer was evaluated using in vitro and in vivo methods, including analysis of cells growth or apoptosis, 3D spheroids culture, and animal xenografts. Results PRLR pathway activated by PRL could significantly decrease sensitivity of ERα-positive breast cancer cells to tamoxifen. Tamoxifen treatment upregulated transcription of PRLR and could induce significant accumulation of PRLR protein in breast cancer cells by alkalizing lysosomes. Meanwhile, tamoxifen-resistant MCF7 achieved by long-term tamoxifen pressure exhibited both upregulated transcription and protein level of PRLR. Immunotoxin N8-PE24 enhanced sensitivity of breast cancer cells to tamoxifen both in vitro and in vivo. In xenograft models, N8-PE24 significantly enhanced the efficacy of tamoxifen and paclitaxel when treating PRLR-positive triple-negative breast cancer. Conclusions PRL-PRLR axis potentially associates with tamoxifen insensitivity in ERα-positive breast cancer cells. N8-PE24 could inhibit cell growth of the breast cancers and promote drug sensitivity of PRLR-positive breast cancer cells to tamoxifen and paclitaxel. Our study provides a new perspective for targeting PRLR to treat breast cancer.

Abstract A risk factor for thyroid cancer (TC) may be a history of former cancer and cancer therapy. The precise risk of a second primary thyroid carcinoma has not yet been revealed. In this study, we evaluated standardized incidence ratios (SIRs) of second primary thyroid cancer (SPTC) with consideration of different conditions and further analyzed the clinicopathological characteristics and survival of these patients. The cohort was selected from the US Surveillance, Epidemiology, and End Results (SEER) Program between 1975 and 2019. The standardized incidence ratios, morbidity risk, clinicopathological features, and survival of second primary thyroid carcinoma were analyzed. Propensity score matching (PSM) was used to balance covariates. Kaplan–Meier method was performed to assess the survival outcomes. Overall, 7066 patients with SPTC and 83,113 patients with primary TC were identified. The SIR of TC in tumor patients was 1.51/10,000, statistically higher than the natural population (0.94/10,000, P

Abstract Background Non‐small cell lung cancer (NSCLC) is a type of lung cancer that occurs in the cells of the respiratory tract, and its development is influenced by the regulation of circular RNAs (circRNAs). However, the role of circRNA carboxypeptidase A4 (circCPA4) in the progression of NSCLC and the underlying mechanism remain relatively clear. Methods The study utilized both real‐time quantitative polymerase chain reaction (RT‐qPCR) and western blot techniques to evaluate the levels of circCPA4, microRNA‐145‐5p (miR‐145‐5p), alanine, serine, or cysteine‐preferring transporter 2 (ASCT2). To assess cell proliferation, cell counting kit‐8 (CCK8) and 5‐ethynyl‐2′‐deoxyuridine (EdU) assays were performed. Apoptosis was determined using flow cytometry, while cell migration and invasive capacity were evaluated through transwell and wound‐healing assays. Intracellular levels of glutamine, glutamate, and α‐KG were measured using specific kits. The relationship between miR‐145‐5p and circCPA4 or ASCT2 was confirmed using dual‐luciferase reporter assay and RNA immunoprecipitation assay. Results CircCPA4 and ASCT2 RNA levels were elevated, while miR‐145‐5p was downregulated in both NSCLC tissues and cells. Depletion of circCPA4 significantly inhibited NSCLC cell proliferation, migration, invasion, and intracellular levels of glutamine, glutamate, and α‐KG, and promoted apoptosis. Moreover, circCPA4 knockdown delayed tumor growth in vivo. Furthermore, circCPA4 was found to bind to miR‐145‐5p, thereby regulating the progression of NSCLC in vitro. ASCT2 was also identified as a downstream target of miR‐145‐5p, and its upregulation rescued the effects of miR‐145‐5p overexpression on NSCLC cell processes. Conclusion CircCPA4 knockdown inhibited tumor property of NSCLC cells by modulating the miR‐145‐5p/ASCT2 axis.

ABSTRACTBackground Platinum is a commonly used drug for ovarian cancer (OvCa) treatment, but drug resistance limits its clinical application. This study intended to delineate the effects of adipocytes on platinum resistance in OvCa.Methods OvCa cells were maintained in the adipocyte-conditioned medium. Cell viability and apoptosis were detected by CCK-8 and flow cytometry, separately. Proliferation and apoptosis-related protein expression were assayed by western blot. The IC50 values of cisplatin and carboplatin were determined using CCK-8. IGF1 secretion and expression were assayed via ELISA and western blot, respectively. A xenograft model was established, and pathological changes were detected by H&E staining. Proliferation and apoptosis-associated protein expression was assessed via IHC.Results Adipocytes promoted the viability and repressed cell apoptosis in OvCa, as well as enhancing platinum resistance, while the addition of IGF-1 R inhibitor reversed the effects of adipocytes on proliferation, apoptosis, and drug resistance of OvCa cells. Treatment with different concentrations of Ojeok-san (OJS) inhibited the adipocyte-induced platinum resistance in OvCa cells by suppressing IGF1. The combined treatment of OJS and cisplatin significantly inhibited tumour growth in vivo with good mouse tolerance.Conclusion In summary, OJS inhibited OvCa proliferation and platinum resistance by suppressing adipocyte paracrine IGF1 secretion.

Neural cell adhesion molecule L1 (L1CAM) is a cell-surface glycoprotein involved in cancer occurrence and migration. Up to today, L1CAM-targeted therapy appeared limited efficacy in clinical trials although quite a few attempts by monoclonal antibody (mAb) or chimeric antigen receptor T-cell therapy (CAR-T) have been reported. Therefore, the development of new effective therapies targeting L1CAM is highly desirable. It has been demonstrated that T cell-engaging bispecific antibody (TCE) plays an effective role in cancer immunotherapy by redirecting the cytotoxic activity of CD3+ T cells to tumor cells, resulting in tumor cell death. In this study, we designed and characterized a novel bispecific antibody (CE7-TCE) based on the IgG-(L)-ScFv format, which targets L1CAM and CD3 simultaneously. In vitro, CE7-TCE induced specific killing of L1CAM-positive tumor cells through T cells. In vivo, CE7-TCE inhibited tumor growth in human peripheral blood mononuclear cell/tumor cell co-grafting models. To overcome the adaptive immune resistance (AIR) that impairs the efficacy of TCEs, we conducted a combination therapy of CE7-TCE with Pembrolizumab (anti-PD1 mAb), which enhanced the anti-tumor activity of CE7-TCE. Our results confirmed the feasibility of using L1CAM as a TCE target for the treatment of solid tumors and revealed the therapeutic potential of CE7-TCE combined with immune checkpoint inhibitors.

As the requirement for image uploads in various systems continues to grow, image segmentation has become a critical task for subsequent operations. Balancing the efficiency and accuracy of image segmentation is a persistent challenge. This paper focuses on threshold-based grayscale image segmentation methods and proposes a fully automated approach. The approach begins with the implementation of an improved OTSU algorithm to determine the optimal dynamic threshold, enabling the segmentation process to adjust adaptively to varying image backgrounds. A novel method for selecting image center points is introduced to address the issue of poor segmentation when the center point falls outside the segmentation foreground area. To further enhance the algorithm’s generalization capability and accuracy, a continuity detection-based method is developed to determine the start and end points of the segmentation foreground. Compared with traditional algorithms, tests on sample images of four different scales revealed that the proposed algorithm achieved average improvements in accuracy, precision, and recall rates of 14.97%, 1.28%, and 17.33%, respectively, with processing speed remaining largely unaffected. Ablation experiments further validated the effectiveness of using different strategy combinations, with the combination of all three strategies resulting in significant improvements in accuracy and recall rates by 15.51% and 16.72%, respectively.

Periostin, as a unique extracellular matrix, is mainly produced during ontogeny and in adult connective tissues that bear mechanical loads, such as heart valves, skin, periodontal ligaments, tendons, and bones. By binding to the integrin on the cell surface and activating Wnt/β-catenin, NF-κB, Fak and other signaling pathways, it regulates the tissues in vivo positively or negatively, and also has different effects on the occurrence and development of various diseases. Periostin is an important factor, which can promote cell proliferation, stimulate tissue repair and maintain the integrity of the structure and function of connective tissue. It also promotes the formation, regeneration and repairation of bone. Recent studies have shown that periostin is important in bone metabolic diseases. The increased expression of periostin can affect bone mineral density at different sites, and its relationship with traditional biochemical markers of bone turnover has not been conclusively established. This article reviews the research results and potential applications of periostin in osteoporosis.

Water sealing performance is important for underground water-sealed oil storage (UWSOS). The key issues concerning water sealing performance mainly include the permeability of fractured rock mass (FRM), water-sealed safety (WSS), water curtain performance, and prediction and control of water inflow. This paper reviews the progress of above four key issues on water sealing performances. First, the permeability of an FRM is the basis of water sealing performance, and several commonly used permeability test methods and spatial variation characteristics of permeability are outlined. Second, the current water sealing criteria are compared, and the evaluation methods of WSS are summarized. Third, the design parameters and efficiency evaluation of water curtain systems (WCSs) are introduced. The water inflow of oil storage caverns (OSCs) can reflect the water sealing effect, and the prediction methods and control measures of water inflow are also summarized. Finally, the advantages and disadvantages of the current research are discussed, and the potential research directions are pointed out, such as optimization of water sealing criteria and FRM model, quantitative evaluation of WCS efficiency, accurate prediction of water inflow, and improvement of grouting technology.

This paper aims to examine the association between green innovation and the cost of equity in China. This study relies on the investors’ base perspective and shareholders’ perceived risk perspective to investigate the relation between green innovation and the cost of equity in China. The paper uses firm-fixed effect regression for a sample of Chinese public companies for the period 2008–2018. The authors find a negative relationship between green innovation and the cost of equity capital. This negative association is found to be more pronounced for less financially constrained firms, during periods of high economic policy uncertainty, and for firms with a strong internal control environment. Finally, the paper shows that the negative association became more pronounced after the passage of the Environmental Protection Law of China in 2012. The results remain robust to possible endogeneity concerns. This study contributes to the green innovation literature by documenting that shareholders favorably view firms implementing green innovation policies. The study also has policy implications for Chinese regulators in improving the green credit policy.

Background: Uncemented short stems have been shown to optimize load distribution on the proximal femur, reducing stress shielding and preserving bone mass. However, they may adversely affect the initial stability of the stems. To date, most research conducted on short stems has predominantly centered on uncemented stems, leaving a notable dearth of investigations encompassing cemented stems. Therefore, this study aimed to investigate the length of cemented stems on the transmission of femoral load patterns and assess the initial stability of cemented short stems.Method: A series of finite element models were created by gradient truncation on identical cemented stem. The impact of varying lengths of the cemented stem on both the peak stress of the femur and the stress distribution in the proximal femur (specifically Gruen zones 1 and 7) were assessed. In addition, an experimental biomechanical model for cemented short stem was established, and the initial stability was measured by evaluating the axial irreversible displacement of the stem relative to the cement.Result: The maximum von-Mises stress of the femur was 58.170 MPa. Spearman correlation analysis on the shortened length and von-Mises stress of all nodes in each region showed that the p-values for all regions were less than 0.0001, and the correlation coefficients (r) for each region were 0.092 (Gruen Zone 1) and 0.366 (Gruen Zone 7). The result of the biomechanical experiment showed that the irreversible axial displacement of the stem relative to cement was −870 μm (SD 430 μm).Conclusion: Reducing the length of a cemented stem can effectively enhance the proximal load of the femur without posing additional fracture risk. Moreover, the biomechanical experiment demonstrated favorable initial stabilities of cemented short stems.

ObjectivesObservational studies have demonstrated that household income is associated with morbidity of mental disorders. However, a causal relationship between the two factors remains unclear. Therefore, we investigated the causal relationship between household income status and genetic liability of mental disorders using a bidirectional Mendelian randomization (MR) study.MethodsThis MR study included a large cohort of the European population from publicly available genome-wide association study datasets. A random-effects inverse-variance weighting model was used as the main standard, with MR-Egger regression, weighted median, and maximum likelihood estimations performed concurrently as supplements. Sensitivity analysis, consisting of heterogeneity and horizontal pleiotropy tests, was performed using Cochran’s Q test, MR-Egger intercept, and MR-PRESSO tests to ensure the reliability of the conclusions.ResultsA higher household income tended to be associated with a lower risk of genetic liability for depression (odds ratio [OR]: 0.655, 95% confidence interval [CI] = 0.522–0.822, p

Leaf morphology plays a crucial role in plant classification and provides a significant model for studying plant diversity while directly impacting photosynthetic efficiency. In the case of melons, leaf shape not only influences production and classification but also represents a key genetic trait that requires further exploration. In this study, we utilized forward genetics to pinpoint a recessive locus, dubbed Cmrl (Round leaf), which is responsible for regulating melon leaf shape. Through bulked segregant analysis sequencing and extensive evaluation of a two-year F2 population, we successfully mapped the Cmrl locus to a 537.07 kb region on chromosome 8 of the melon genome. Subsequent genetic fine-mapping efforts, leveraging a larger F2 population encompassing 1322 plants and incorporating F2:3 phenotypic data, further refined the locus to an 80.27 kb interval housing five candidate genes. Promoter analysis and coding sequence cloning confirmed that one of these candidates, MELO3C019152.2 (Cmppr encoding a pentatricopeptide repeat-containing family protein, Cmppr), stands out as a strong candidate gene for the Cmrl locus. Notably, comparisons of Cmrl expressions across various stages of leaf development and different leaf regions suggest a pivotal role of Cmrl in the morphogenesis of melon leaves.

The infiltration of immune cells can significantly affect the prognosis and immune therapy of patients with cervical squamous cell carcinoma (CSCC). This study aimed to explore key immune cell-related genes in the tumorigenesis and prognosis of CSCC. The module significantly related to immunity was screened by weighted gene co-expression network analysis (WGCNA) and ESTIMATE analysis, followed by correlation analysis with clinical traits. Key candidate genes were intersected with the protein–protein interaction (PPI) network genes for immune-related genes. The relationship between immune cell infiltration and key genes was analyzed. Tumor immune dysfunction and exclusion (TIDE) and immunophenoscore (IPS) predicted the response to immunotherapy in CSCC patients. Clinically, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry were manipulated for analyzing the changes in mRNA and protein expression of key genes in cancer. Western blot was conducted to assess the correlation between key genes and immune infiltration. The brown module was notably associated with the immune microenvironment of CSCC, from which three immune-related key genes (TYROBP, CCL5, and HLA-DRA) were obtained. High expression of these genes was significantly positively associated with the infiltration abundance of T cells, B cells, and other immune cells. High expression levels of three key genes were confirmed in para-cancer tissue and correlated with the abundance of immune cells. The high-expression group of key genes was more sensitive to immunotherapy. We provide a theoretical basis for searching for potential targets for effective treatment and diagnosis of CSCC and provide new ideas for developing novel immunotherapy strategies.

Abstract Background Significant intertumoral heterogeneity exists as antitumor treatment is introduced. Heterogeneous therapeutic responses are conventionally evaluated by imaging examinations based on Response Evaluation Criteria in Solid Tumors (RECIST); nevertheless, there are increasing recognitions that they do not fully capture patient clinical benefits. Currently, there is a paucity of data regarding the clinical implication of biological responses assessed by liquid biopsy of on-treatment circulating tumor DNA (ctDNA). Here, we investigated whether biological response evaluated by ctDNA kinetics added critical information to the RECIST, and whether integrating on-treatment biological response information refined risk stratification of cancer patients. Methods In this population-based cohort study, we included 821 patients with Epstein-Barr virus (EBV)-associated nasopharynx of head and neck cancer (NPC) receiving sequential neoadjuvant chemotherapy (NAC) and chemoradiotherapy (CRT), who had pretreatment and on-treatment cfEBV DNA and magnetic resonance imaging (MRI) surveillance. Biological responses evaluated by cfEBV DNA were profiled and compared with conventional MRI-based RECIST evaluation. The inverse probability weighting (IPW)-adjusted survival analysis was performed for major survival endpoints. The Cox proportional hazard regression [CpH]-based model was developed to predict the on-treatment ctDNA-based individualized survival. Results Of 821 patients, 71.4% achieved complete biological response (cBR) upon NAC completion. RECIST-based response evaluations had 25.3% discordance with ctDNA-based evaluations. IPW-adjusted survival analysis revealed that cfEBV DNApost-NAC was a preferential prognosticator for all endpoints, especially for distant metastasis. In contrast, radiological response was more preferentially associated with locoregional recurrence. Intriguingly, cfEBV DNApost-NAC further stratified RECIST-responsive and non-responsive patients; RECIST-based non-responsive patients with cBR still derived substantial clinical benefits. Moreover, detectable cfEBV DNApost-NAC had 83.6% prediction sensitivity for detectable post-treatment ctDNA, which conferred early determination of treatment benefits. Finally, we established individualized risk prediction models and demonstrated that introducing on-treatment ctDNA significantly refined risk stratification. Conclusions Our study helps advance the implementation of ctDNA-based testing in therapeutic response evaluation for a refined risk stratification. The dynamic and refined risk profiling would tailor future liquid biopsy-based risk-adapted personalized therapy.

Polyphenols containing styrene pyranone skeleton are unique to porous fungi. Inonotus obliquus (IO) is a medicinal and edible porous fungus. Twelve phenolic compounds containing four styryl pyranone polyphenols from IO were isolated and identified in this work. The antioxidant ability of the isolates was characterized utilizing the ferric reducing antioxidant power (FRAP) assay and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) radical scavenging test. Styrylpyranone polyphenols, especially methylinoscavin B, could capture free radicals better than other phenolic compounds, and quantum chemical calculations also confirmed this evaluation. The density functional theory (DFT) calculation data showed that Styrylpyranone polyphenols, especially methylinoscavin B, have a lower energy gap, higher softness and higher electronic chemical potential than other phenolic compounds. The bond dissociation energy values of the bond in C7ʹ O–H of the methylinoscavin B molecule are less than those in C11 and C6ʹ O–H when reacting with ∙OOH (selected as a representative free radical). On the basis of calculations, hydrogen atom transfer (HAT) is supposed to be a preferred mechanism over single electron transfer (SET) when phenolic compounds react with free radicals. Moreover, after treatment with final concentrations of 0.5, 1, 2, 3, 4 and 5 μM phelligridin E (PHE), the activity of SOD1 increased by 70.15%, 11.36%, 145.45%, 172.73%, 205.05% and 275.23%, respectively. The molecular dynamics simulation (MD) study of PHE employed SOD1 (PDB ID: 6FN8). The MD results showed that the hydrogen bonds between ASP147 of SOD1 and PHE promote GLU223-ARG224 to form a stable C coil after combining with PHE. The formation of the C Coil enhanced the stability of the electrostatic loop (EL) of SOD1 and the rate of diffusion of the superoxide anion to the active site. Styrylpyrone polyphenols of Inonotus obliquus origin have the potential to be a source of vigorous free radical scavengers and antioxidant enzyme activators.

Underground water-sealed oil storage caverns constructed in island environments is a promising approach for expanding oil storage caverns. However, few researchers have studied the risks of seawater intrusion and the distribution characteristics of intrusion interfaces in large underground water-sealed oil storage caverns in island environments. In this paper, we established a visualized physical simulation platform to investigate the characteristics and control measures of seawater intrusion in single fracture of rock masses within island underground water-sealed oil storage caverns. In addition, the effects of the excavation of caverns, the distance between the cavern and coast, fracture width, seawater level, oil storage stage, water curtain, and water injection pressure were evaluated. The results show that excavation of oil storage caverns carries the risk of seawater intrusion. Specifically, reducing the distance between the oil storage caverns and the coast, increasing the fracture width, and raising the seawater level all contribute to accelerated seawater intrusion into the caverns. However, the vertical water curtain can effectively inhibit seawater intrusion, and increasing the injection pressure of vertical water curtain can avoid the risk of seawater intrusion into the caverns. The research results provide an experimental basis for the study of seawater intrusion in underground oil storage caverns in island environments.

Abstract Random lasers with low spatial coherence have important potential applications in speckle‐free imaging and displaying. Here, an angular spectra (AS) tunable random laser is proposed through directly coupling a microcavity with a commercial optical fiber. The local in‐plane AS distributions of the random lasing can be separately tuned by selectively using coupling filtering, free transmission, and intensity modulation. The obtained random lasing has the characteristics of non‐polarization and ring AS with distribution tunability. The unique properties endow the lasing as a promising illumination source for biological imaging. An excellent image with speckle‐free and high contrast is thus achieved with a maximal contrast improvement factor of 638% relative to that under the common white lighting. The results indicate that the designed AS‐tunable random laser has great application values in the fields of biological imaging, display, integration optics, and optical physics.

Abstract Mid-infrared (mid-IR) sensors consisting of silicon nitride (SiN) waveguides were designed and tested to detect volatile organic compounds (VOCs). SiN thin films, prepared by low-pressure chemical vapor deposition (LPCVD), have a broad mid-IR transparent region and a lower refractive index (nSiN = 2.0) than conventional materials such as Si (nSi = 3.4), which leads to a stronger evanescent wave and therefore higher sensitivity, as confirmed by a finite-difference eigenmode (FDE) calculation. Further, in-situ monitoring of three VOCs (acetone, ethanol, and isoprene) was experimentally demonstrated through characteristic absorption measurements at wavelengths λ = 3.0–3.6 μm. The SiN waveguide showed a five-fold sensitivity improvement over the Si waveguide due to its stronger evanescent field. To our knowledge, this is the first time SiN waveguides are used to perform on-chip mid-IR spectral measurements for VOC detection. Thus, the developed waveguide sensor has the potential to be used as a compact device module capable of monitoring multiple gaseous analytes for health, agricultural and environmental applications.

Konjac glucomannan (KGM) is a natural polysaccharide derived from konjac, which has been widely used in various fields due to its numerous beneficial properties. However, the high viscosity and water absorption of KGM limit its application. Compared with KGM, Konjac glucomannan oligosaccharides (KGMOS) have higher water solubility and stronger application value. In this paper, a novel mannanase KgManA was cloned from Klebsiella grimontii to develop a new KGMOS-producing enzyme. Bioinformatic analysis shows that the structural similarity between KgManA and other enzymes was less than 18.33%. Phylogenetic analysis shows that KgManA shares different branches with the traditional mannanases containing the CMB35 domain, indicating that it is a novel mannanase. Then, the enzymatic properties were determined and substrate specificity was characterized. Surprisingly, KgManA is stable in a very wide pH range of 3.0 to 10.0; it has a special substrate specificity and seems to be active only for mannans without galactose in the side chain. Additionally, the three-dimensional structure of the enzyme was simulated and molecular docking of the mannotetraose substrate was performed. As far as we know, this is the first report to characterize the enzymatic properties and to simulate the structure of mannanase from K. grimontii. This work will contribute to the development and characterization of novel K. grimontii-derived mannanases. The above results indicate that KgManA is a promising tool for the production of KGMOS.

To accurately simulate realistic pedestrian evacuation from a fire, a cellular automaton model of the dynamic changes in pedestrian movement parameters is developed in conjunction with fire dynamics software. The fire dynamics software is used to simulate the spread of smoke within the scene to obtain visibility and CO concentration data within the scene. We imported the smoke data into the cellular automata and adjusted the pedestrian movement speed over time, resulting in simulation data that closely align with reality. The results show that for the single-room scenario, as pedestrian density increased from 0.1 to 0.5 persons per square meter (p/m2), the influence of the percentage of pedestrians familiar with their location on evacuation efficiency decreased from 44.93% to 24.52%. Conversely, in the multi-room scenario, it increased from 23.68% to 38.79%. The proportion of pedestrians less affected by smoke decreases and stabilizes as the CO yield increases. In the single-room scenario, when the CO yield is below 10%, the crowd with a low percentage of pedestrians familiar with the site is more affected by smoke than those with a high percentage. In the multi-room scenario, the victimization rate of the crowd follows an increasing-then-decreasing curve, ultimately stabilizing with changes in CO yield.

Abstract Fibroblast growth factor-21 (FGF-21) performs a wide range of biological functions in organisms. Here, we report for the first time that FGF-21 suppresses thrombus formation with no notable risk of bleeding. Prophylactic and therapeutic administration of FGF-21 significantly improved the degree of vascular stenosis and reduced the thrombus area, volume and burden. We determined the antithrombotic mechanism of FGF-21, demonstrating that FGF-21 exhibits an anticoagulant effect by inhibiting the expression and activity of factor VII (FVII). FGF-21 exerts an antiplatelet effect by inhibiting platelet activation. FGF-21 enhances fibrinolysis by promoting tissue plasminogen activator (tPA) expression and activation, while inhibiting plasminogen activator inhibitor 1 (PAI-1) expression and activation. We further found that FGF-21 mediated the expression and activation of tPA and PAI-1 by regulating the ERK1/2 and TGF-β/Smad2 pathways, respectively. In addition, we found that FGF-21 inhibits the expression of inflammatory factors in thrombosis by regulating the NF-κB pathway.

Radiotherapy is the mainstay treatment for nasopharyngeal carcinoma (NPC). Here the authors show that the deubiquitinase, USP44, increases radiosensitivity of NPC cells by promoting the degradation of Ku80, and thus enhancing the levels of DNA damage.

IntroductionMany researchers used machine learning (ML) to predict the prognosis of breast cancer (BC) patients and noticed that the ML model had good individualized prediction performance.ObjectiveThe cohort study was intended to establish a reliable data analysis model by comparing the performance of 10 common ML algorithms and the the traditional American Joint Committee on Cancer (AJCC) stage, and used this model in Web application development to provide a good individualized prediction for others.MethodsThis study included 63145 BC patients from the Surveillance, Epidemiology, and End Results database.ResultsThrough the performance of the 10 ML algorithms and 7th AJCC stage in the optimal test set, we found that in terms of 5-year overall survival, multivariate adaptive regression splines (MARS) had the highest area under the curve (AUC) value (0.831) and F1-score (0.608), and both sensitivity (0.737) and specificity (0.772) were relatively high. Besides, MARS showed a highest AUC value (0.831, 95%confidence interval: 0.820-0.842) in comparison to the other ML algorithms and 7th AJCC stage (all P < 0.05). MARS, the best performing model, was selected for web application development (https://w12251393.shinyapps.io/app2/).ConclusionsThe comparative study of multiple forecasting models utilizing a large data noted that MARS based model achieved a much better performance compared to other ML algorithms and 7th AJCC stage in individualized estimation of survival of BC patients, which was very likely to be the next step towards precision medicine.

Wheat seedlings are becoming popular for its high nutritional value. Effects of White (W), White + Red (WR), and White + Blue (WB) light-emitting diodes (LEDs) treatments on growth, nutritional characteristics and antioxidant properties of wheat seedlings were studied in a plant factory. The results showed that height, leaf area, shoot fresh, and shoot dry weight per wheat seedling were the highest under WR at 13 and 22 days after planting. Soluble sugar content in leaves and stems were 22.3 and 65% respectively higher under WB than those under W. Soluble protein content in leaves and stems were 36.8 and 15.2% respectively lower under WR than those under W. Contents of total flavonoids, glutathione (GSH) and ascorbic acid (ASA) in leaves were the highest under WB, whereas malondialdehyde (MDA) content in leaves was the lowest under WB. The activities of antioxidant enzymes [superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX)] in leaves and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability were also the highest under WB. In conclusion, WR promoted the growth of wheat seedlings, and WB promoted antioxidant level and nutritional accumulation. This study provides guidance for wheat seedlings to carry out preferential production (biomass or quality).

Pea sprouts have rich nutrition and are considered good for heart health. In this study, the kaspa peas and black-eyed peas were chosen to clarify the effect of different LED spectral combinations on the growth, yield, and nutritional quality of pea sprouts under long photoperiod (22 h light/2 h dark). The results showed that the two pea varieties responded differently to light spectral combinations. Black-eyed pea sprouts had higher plant height, fresh weight per plant, dry weight per plant, soluble sugar content, and lower malondialdehyde (MDA) content than kaspa peas under the same light treatment. Compared with white light, red-to-blue ratio of 2:1 significantly increased peroxidase (POD) and superoxide dismutase (SOD) activity, soluble sugar and soluble protein content of kaspa pea sprouts, and decreased MDA content of black-eyed pea sprouts. Blue light was negatively correlated with the plant height of pea sprouts and positively correlated with SOD activity, vitamin C, soluble sugar, and soluble protein content. Antioxidant capacity, yield, and nutritional quality of black-eyed pea sprouts were higher than those of kaspa pea sprouts under the same light treatment. Blue light improved the nutritional quality of pea sprouts. Compared with other light treatments, the red-to-blue ratio of 2:1 was more conducive to improving the antioxidant capacity and nutritional quality of pea sprouts under long photoperiod.

Chemoresistance is the leading cause of poor prognosis in head and neck squamous cell carcinoma (HNSC); however, promising biomarkers to identify patients for stratified chemotherapy are lacking. Sideroflexin 3 (SFXN3) is an important mitochondrial serine transporter during one-carbon metabolism, which is involved in the proliferation of cancer cells. However, the specific role of SFXN3 in HNSC remains unknown. In this study, we performed expression and survival analysis for SFXN3 in pan-cancer using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) and found that SFXN3 served as a potential oncogene in HNSC. Notably, SFXN3 expression was found to be positively associated with enriched tumor-infiltrating macrophages, other immune suppressive cells, and immune checkpoint expression and resistance to paclitaxel. Gene, clinical, and immune variables included in the univariate and multivariate analyses showed that SFXN3 expression was an independent risk factor. Moreover, the LINC01270/hsa-miR-29c-3p/SFXN3 axis was identified as the most likely upstream non-coding RNA-related pathway of SFXN3 in HNSC using bioinformatic analysis, expression analysis, correlation analysis, and survival analysis. Taken together, our findings demonstrated that a non-coding RNA-mediated high expression of SFXN3 is a prognostic biomarker and is associated with the immunosuppressive microenvironment in HNSC.

Haemonchus contortus poses a severe hazard to the healthy development of the sheep industry and threatens the welfare of sheep. Ivermectin is the primary anthelmintic used for the prevention and treatment of H. contortus parasitism. However, the widespread and uncontrolled application of ivermectin has resulted in the development and spread of resistant strains of H. contortus. P-glycoprotein (P-gp) plays important roles in the pharmacology and toxicology of ivermectin, and changes in P-gp expression levels can be used to analyze the resistance of H. contortus to ivermectin. This study aimed to analyze the effects of ivermectin on P-gp expression in H. contortus L3 larvae isolated from China and to evaluate whether changes in P-gp expression levels can be used to analyze resistant H. contortus strains. In the absence of drug treatment, the ivermectin-resistant strains isolated in China showed increased expression of P-gp11 (p < 0.01) compared with sensitive strains from elsewhere, whereas the expressions of P-gp2 and P-gp9.1 were downregulated (p < 0.01). When the same strain was compared before and after drug treatment, obvious differences in expression were observed between the different strains. Ivermectin-induced P-gp expression was found to be very complex among the L3 larvae of different strains. In addition, it was confirmed that using P-gp to determine ivermectin resistance in H. contortus strains from different geographic environments can yield different results.

The main objective of this article is to investigate the dynamical transition for a 3-component Lotka-Volterra model with diffusion. Based on the spectral analysis, the principle of exchange of stability conditions for eigenvalues is obtained. In addition, when $\delta_0\delta_1$, the first eigenvalue is real. Generically, the first eigenvalue is simple and all three types of transition are possible. In particular, the transition is mixed if $\int_{\Omega}e_{k_0}^3dx\neq 0$, and is continuous or jump in the case where $\int_{\Omega}e_{k_0}^3dx= 0$. In this case we also show that the system bifurcates to two saddle points on $\delta 0$, and bifurcates to two stable singular points on $\delta>\delta_1$ as $\tilde{\theta}< 0$ where $\tilde{\theta}$ depends on the system parameters.

Abstract Recently, the traffic application based on vision in the single traffic‐monitoring scene has been widely studied and developed. However, cross‐regional research is still in its infancy. In order to help solve the application of cross‐regional traffic surveillance scenarios, this paper proposes a more reliable and accurate road scene mosaic method under multi‐camera surveillance. The mosaic road panorama contains physical information, which can be used to achieve a cross‐regional measurement. It also lays the foundation for vehicle spatial location, vehicle speed and traffic incident detection across regions. First, the mapping relationship between the three‐dimensional sub‐world coordinates and their corresponding two‐dimensional image coordinates is established by camera calibration. Second, the projection transformation relationship between two cameras is established by two sub‐world coordinate systems and their common information. Finally, we use the proposed inverse projection idea and translation vector relationship to complete the mosaic of two traffic‐monitoring road scenes. The experimental results show that the camera calibration accuracy can reach more than 97% in a single scene. The measurement accuracy of the mosaic block is over 95%. The experimental results show that the proposed method has a higher accuracy, which has great value in related theoretical research and practical applications.

A major problem faced by the agricultural industry is the resistance of Haemonchus contortus to anthelmintic drugs. For a better understanding of the response of H. contortus to IVM and for the screening of drug-resistance-related genes, we used RNA sequencing and isobaric tags for relative and absolute quantification (iTRAQ) technology to detect the transcriptomic and proteomic changes in H. contortus after ivermectin treatment. An integrated analysis of the two omics showed that the differentially expressed genes and proteins were significantly enriched in the pathways of amino acid degradation, the metabolism of xenobiotics by cytochrome P450, the biosynthesis of amino acids, and the tricarboxylic acid cycle. We found that the upregulated UDP-glycosyltransferases (UGT), glutathione S-transferase (GST), cytochrome P450 (CYP), and p-glycoprotein (Pgp) genes play important roles in drug resistance in H. contortus. Our work will help in the understanding of the transcriptome and proteome changes in H. contortus after IVM and will facilitate the discovery of genes related to drug resistance. This information can be further applied to increase the understanding of the response of IVM in relation to H. contortus.

Abstract Background The activation of NOD-like receptor protein 3 (NLRP3) inflammasome-dependent pyroptosis has been shown to play a vital role in the pathology of manganese (Mn)-induced neurotoxicity. Sodium para-aminosalicylic acid (PAS-Na) has a positive effect on the treatment of manganism. However, the mechanism is still unclear. We hypothesized that PAS-Na might act through NLRP3. Methods The microglial cell line BV2 and male Sprague-Dawley rats were used to investigate the impacts of PAS-Na on Mn-induced NLRP3 inflammasome-dependent pyroptosis. The related protein of the NF-κB pathway and NLRP3-inflammasome-dependent pyroptosis was detected by western blot. The reactive oxygen species and mitochondrial membrane potential were detected by immunofluorescence staining and flow cytometry. The activation of microglia and the gasdermin D (GSDMD) were detected by immunofluorescence staining. Results Our results showed that Mn treatment induced oxidative stress and activated the NF-κB pathway by increasing the phosphorylation of p65 and IkB-α in BV2 cells and in the basal ganglia of rats. PAS-Na could alleviate Mn-induced oxidative stress damage by inhibiting ROS generation, increasing mitochondrial membrane potential and ATP levels, thereby reducing the phosphorylation of p65 and IkB-α. Besides, Mn treatment could activate the NLRP3 pathway and promote the secretion of IL-18 and IL-1β, mediating pyroptosis in BV2 cells and in the basal ganglia and hippocampus of rats. But an inhibitor of NF-κb (JSH-23) treatment could significantly reduce LDH release, the expression of NLRP3 and Cleaved CASP1 protein and IL-1β and IL-18 mRNA level in BV2 cells. Interestingly, the effect of PAS-Na treatment in Mn-treated BV2 cells is similar to those of JSH-23. Besides, immunofluorescence results showed that PAS-Na reduced the increase number of activated microglia, which stained positively for GSDMD. Conclusion PAS-Na antagonized Mn-induced NLRP3 inflammasome dependent pyroptosis through inhibiting NF-κB pathway activation and oxidative stress.

In this study, an effective approach has developed to solidify phosphorus, fluorine and heavy metals in phosphogypsum by using carbide slag(CS) and polymer, and the effect of carbide slag and polymer addition on the pH and the speciations of phosphorus, fluorine in phosphogypsum has discussed in detail. The experimental results showed that in the carbide slag modified phosphogypsum system, soluble phosphorus and fluoride were significant fixed and converted into Ca3(PO4)2, CaF2 and other stable precipitates. The pH-related leaching test results indicated that there was little significant relationship between the total phosphorus leaching concentration and pH under neutral and alkaline conditions. Fluorapatite is the control phase of phosphorus in the phosphogypsum system, and the fluorite and fluorapatite are the main control phases of fluorine leaching. After long-term leaching, the proportion of the control phase of fluorite was reduced. In the polymer modified phosphogypsum system, large amount of soluble phosphorus and fluorine were solidified, which achieve high effective solidification of phosphorus and fluorine. The pH-related leaching test showed that the polymer has a significant effect on phosphorus and fluorine under different pH conditions. Besides, the curing effect has a significant relationship with pH. At the same time, carbide slag and polymer have a certain effect on the conversion between the speciations of heavy metals in the system. The experimental results showed that the pH, phosphorus, fluorine and heavy metals in the carbide slag-phosphogypsum (CS-PG) system meet the requirements of the ''Integrated Wastewater Discharge Standard (GB 8978–1996)'' of China.

Abstract Background Circular RNAs (circRNAs), a new type of noncoding RNA (ncRNA), have been identified as significant gene expression regulators and are involved in cancer progression. However, the roles of circRNAs in nasopharyngeal carcinoma (NPC) remain largely unknown. Methods Here, the expression profile of circRNAs in a pair of NPC cell lines with different metastatic abilities (S18 and S26 cells) was analyzed by RNA-sequencing. Quantitative reverse transcription PCR was used to detect the expression level of circCRIM1 in NPC cells and tissues. Then, function experiments in vitro and in vivo were performed to evaluate the effects of circCRIM1 on NPC metastasis and EMT. Mechanistically, RNA immunoprecipitation, luciferase reporter assay, pull-down assay with biotinylated miRNA, fluorescent in situ hybridization were performed to confirm the interaction between circCRIM1 and miR-422a in NPC. The clinical value of circCRIM1 was evaluated in NPC metastasis and chemosensitivity. Results We identified that circCRIM1 was upregulated in highly metastatic NPC cells. CircCRIM1 was also overexpressed in NPC tissues with distant metastasis, and its overexpression promoted NPC cell metastasis and EMT. Mechanistically, circCRIM1 competitively bound to miR-422a and prevented the suppressive effects of miR-422a on its target gene FOXQ1, which finally led to NPC metastasis, EMT and docetaxel chemoresistance. Furthermore, high circCRIM1 expression was associated with unfavorable survival in NPC patients. We established a prognostic model based on circCRIM1 expression and N stage that effectively predicted the risk of distant metastasis and treatment response to docetaxel-containing induction chemotherapy in NPC patients. Conclusions Our findings reveal the critical role of circCRIM1 specifically in promoting NPC metastasis and chemoresistance via a ceRNA mechanism and provide an exploitable biomarker and therapeutic target for prognosis and treatment resistance in NPC patients.

Overexpression of protein tyrosine phosphatase 1B (PTP1B) induces insulin resistance in various basic and clinical research. In our previous work, a synthetic oleanolic acid (OA) derivative C10a with PTP1B inhibitory activity has been reported. However, C10a has some pharmacological defects and cytotoxicity. Herein, a structure-based drug design approach was used based on the structure of C10a to elaborate the smaller tricyclic core. A series of tricyclic derivatives were synthesised and the compounds 15, 28 and 34 exhibited the most PTP1B enzymatic inhibitory potency. In the insulin-resistant human hepatoma HepG2 cells, compound 25 with the moderate PTP1B inhibition and preferable pharmaceutical properties can significantly increase insulin-stimulated glucose uptake and showed the insulin resistance ameliorating effect. Moreover, 25 showed the improved in vivo antihyperglycaemic potential in the nicotinamide–streptozotocin-induced T2D. Our study demonstrated that these tricyclic derivatives with improved molecular architectures and antihyperglycaemic activity could be developed in the treatment of T2D.

Background. The growing body of evidence indicates aberrant expression of long noncoding RNAs (lncRNAs) in breast cancer. Nevertheless, a few studies have focused on identifying key lncRNAs for patients with luminal A breast cancer. In our study, we tried to find key lncRNAs and mRNAs in luminal A breast cancer. Methods. RNA sequencing was performed to identify differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) in luminal A breast cancer. The protein-protein interaction (PPI), DElncRNA-DEmRNA coexpression, DElncRNA-nearby DEmRNA interaction networks, and functional annotation were performed to uncover the function of DEmRNAs. Online databases were used to validate the RNA sequencing result. The diagnostic value of candidate mRNAs was evaluated by receiver operating characteristic (ROC) curve analysis. Results. A total number of 1451 DEmRNAs and 272 DElncRNAs were identified. Several hub proteins were identified in the PPI network, including TUBB3, HIST2H3C, MCM2, MYOC, NEK2, LIPE, FN1, FOXJ1, S100A7, and DLK1. In the DElncRNA-DEmRNA coexpression, some hub lncRNAs were identified, including AP001528.2, LINC00968, LINC02202, TRHDE-AS1, LINC01140, AL354707.1, AC097534.1, MIR222HG, and AL662844.4. The mRNA expression result of TFF1, COL10A1, LEP, PLIN1, PGM5-AS1, and TRHDE-AD1 in the GSE98793 was consistent with the RNA sequencing result. The protein expression results of TUBB3, MCM2, MYOC, FN1, S100A7, and TFF1 were consistent with the mRNA expression result COL10A1, LEP, PLIN1, PGM5-AS1, and TRHDE-AD1 were capable of discriminating luminal A breast cancer and normal controls. Four lncRNA-nearby and coexpressed mRNA pairs of HOXC-AS3-HOXC10, AC020907.2-FXYD1, AC026461.1-MT1X, and AC132217.1-IGF2 were identified. AMPK (involved LIPE and LEP) and PPAR (involved PLIN1) were two significantly enriched pathways in luminal A breast cancer. Conclusion. This study could be helpful in unraveling the pathogenesis and providing novel therapeutic strategies for luminal A breast cancer.

In this study, Co, Cu, Pd, and Pd/Cu composite metal ions were used to synthesize metal nanoparticles with high efficiency in purifying hydrogen cyanide gas. The pure liquid phase catalytic purification of hydrogen cyanide gas was studied. According to the removal rate, the Pd/Cu composite metal ions had the best purification efficiency among the nanoparticles of different metal types. The removal rate order was Pd/Cu>Pd>Cu>Co. The gas after reaction were analyzed by gas chromatography, and it was found that HCN was converted into CO2, N2 and NH3 by nanoparticles. Then, Pd/Cu composite metal ions with the highest purification efficiency were used to study the electrochemical synergistic liquid-phase catalytic purification of HCN gas. The effects of electrochemical conditions and current on the electro-hydraulic synergistic purification were studied. The removal efficiency of HCN by electrochemical synergistic liquid phase catalysis was better than that by pure liquid phase catalysis. The different nanoparticles before and after HCN absorption were characterized and analyzed to explore the purification process of HCN. The purification mechanism of hydrogen cyanide by Pd-Cu catalyst under applied voltage was studied under certain conditions. During the catalytic reaction, the nano-catalyst was partially dissolved in liquid phase and partially HCN reacts with metal ions on the free or nanoparticles to form complex [Mc(CN)n]2−n. Homogeneous and quasi-homogeneous reactions in liquid phase interweave together to form a more complex reaction system.

Nematodirus causes major economic losses in the development of the livestock industry, as they are common gastrointestinal parasites of cattle, sheep, and other ruminants. The present study investigated Nematodirus infections in sheep in the Hulunbuir and Xilingol Grasslands, two well-known natural pastures in Inner Mongolia, China. The results indicated that the average infection rate was more than 50%. Furthermore, a naturally occurring strain of Nematodirus was obtained using numerous isolation methods in the survey region. Conventional morphology and molecular biology were used to identify the strain. The larval migration inhibition test was used to determine the ivermectin level in the isolated strain. The results indicated that the larvae belonged to the species Nematodirus oiratianus. The strain was found to be ivermectin-resistant. Thus, these results recorded the detailed development processes of Nematodirus eggs, providing novel insights regarding the prevention and control of nematodes by using conventional anthelmintic regimens and by offering valuable species resources for studying anthelmintic resistance in nematodes.

Introduction The COVID-19 pandemic has caused unprecedented disruptions around the world. Adding to the existing stress surrounding pregnancy and childbirth, the threat of infection and social isolation policies may negatively impact pregnant women and new mothers. Literature on the effect of COVID-19 on fear during pregnancy and childbirth experience is limited. As the COVID-19 pandemic continues to affect the global population, it is important to understand how it has impacted pregnant women and new mothers’ experiences worldwide to inform perinatal care and interventions.Methods and analysis This multicountry study involving China and Canada targets to recruit 1000 pregnant women and new mothers who gave birth since 2020 in each participating country. Participants will be recruited online in the local language through mothers’ groups, antenatal and postnatal clinics and hospital wards. All questionnaires will be completed online. Participants’ level of fear, depression and childbirth experience will be assessed along with other sociodemographic, medical and COVID-related measures. Regression models will be used to compare the outcomes among the participating countries.Ethics and dissemination The study has been reviewed and approved by the institutional review boards of the participating countries. Findings will be disseminated in peer-reviewed journals and academic conferences. Results from this study may guide the formulation of future health guidelines and policies in the face of a pandemic.

Accreditation is now widely used to attest for laboratory competence. Although accreditation was originally used to assess products in testing laboratories and still plays an increasingly important role in international trade, it has been expanded to include laboratories in many social fields, including forensic science, medicine, and animal quarantine reference. The accreditation process provides basic requirements for achieving global recognition for laboratory reports. This paper introduces the concept of accreditation and discusses the origins and development of the accreditation system in Chinese biosafety laboratories. This study also reveals the important role of this system in national biosafety management through an examination of the 14-year development of the Chinese biosafety laboratory accreditation system. Keywords: Accreditation, Management, Biosafety laboratories

Abstract Background Most mammary Paget disease (MPD) is associated with underlying in situ or invasive breast cancer. The objective of this study was to compare the clinicopathological characteristics and survival outcomes between breast cancer with Paget disease (PD) and breast cancer alone. Methods From the Surveillance, Epidemiology, and End Results (SEER) database, 2000‐2015, of the US National Cancer Institute, we identified 1569 women who had PD with invasive ductal carcinoma (PD‐IDC) and 1489 women who had PD with ductal carcinoma in situ (PD‐DCIS). Independent demographic and clinicopathological variables as well as survival outcomes of these patients were compared to patients with the corresponding breast cancer without concomitant PD. Results PD‐IDC and PD‐DCIS both had worse survival outcomes and poorer tumor characteristics than the corresponding disease without PD. Contrary to in the breast cancer alone groups, in the breast cancer with PD groups, the HR status (P = 0.182 in PD‐IDC and P = 0.371 in PD‐DCIS), HER2 status (P = 0.788 in PD‐IDC and P = 0.643 in PD‐DCIS), and combined molecular subtype (P = 0.196 in PD‐IDC and P = 0.853 in PD‐DCIS) were not found to affect disease prognosis. After matching tumor characteristics and treatment approaches, PD‐IDC as well as PD‐DCIS exhibited no significant difference in disease prognosis with corresponding IDC and DCIS. Finally, by comparative analysis, a kind of PD‐DCIS (ICD‐O‐3 code 8543/3) showed many invasive behaviors (31.8% of 8543/3 patients had stage I‐III cancer) and was associated with worse survival outcomes than the other type of PD‐DCIS. Conclusions Breast cancer with concomitant PD was associated with more aggressive tumor characteristics and worse survival outcomes. The HR status, HER2 status, and combined molecular subtype could not affect the prognosis of breast cancer with PD. Moreover, a portion of the PD‐DCIS cases were invasive breast cancer cases that required special treatment.

Uterine leiomyosarcoma has the characteristics of high malignancy, a poor prognosis, and a high recurrence rate. Surgery is the main treatment option, supplemented by chemotherapy and radiotherapy. We report on a patient with recurrent uterine leiomyosarcoma who was treated with high-intensity focused ultrasound combined with chemotherapy. Tumor growth was controlled and the patient’s survival time was prolonged. High-intensity focused ultrasound combined with chemotherapy may thus provide a new treatment strategy for patients with recurrent and surgically difficult uterine leiomyosarcoma.

Wear occurring at the bearing surface and the consequent generation of wear debris has been identified as the primary cause of aseptic loosening in metal-on-polyethylene (MoP) hip joint replacements. The accurate estimation of volume change in polyethylene cups due to creep and wear is, therefore, an important step for identifying the cause of failure and improving the longevity of MoP prosthesis. The purposes of this study were to present and apply a co-ordinate measuring machine (CMM)-based method for assessing the volume change of retrieved components due to wear and creep by using a combination of CMM data and a bespoke computer programme. The method was firstly validated against the standard gravimetric technique, and then applied to four retrieved polyethylene cups for wear assessment and analysis. The results show that the volume changes calculated using the present method match well with those assessed through the gravimetric technique. The CMM-based method presented in the study is capable of effectively and reliably determining the volume change and characterising the wear patch of retrieved components from MoP hip joint replacements.

Bone scaffolds are widely used as one of the main bone substitute materials. However, many bone scaffold microstructure topologies exist and it is still unclear which topology to use when designing scaffold for a specific application. The aim of the present study was to reveal the mechanism of the microstructure-driven performance of bone scaffold and thus to provide guideline on scaffold design. Finite element (FE) models of five TPMS (Diamond, Gyroid, Schwarz P, Fischer-Koch S and F-RD) and three traditional (Cube, FD-Cube and Octa) scaffolds were generated. The effective compressive and shear moduli of scaffolds were calculated from the mechanical analysis using the FE unit cell models with the periodic boundary condition. The scaffold permeability was calculated from the computational fluid dynamics (CFD) analysis using the 4×4×4 FE models. It is revealed that the surface-to-volume ratio of the Fischer-Koch S-based scaffold is the highest among the scaffolds investigated. The mechanical analysis revealed that the bending deformation dominated structures (e.g., the Diamond, the Gyroid, the Schwarz P) have higher effective shear moduli. The stretching deformation dominated structures (e.g., the Schwarz P, the Cube) have higher effective compressive moduli. For all the scaffolds, when the same amount of change in scaffold porosity is made, the corresponding change in the scaffold relative shear modulus is larger than that in the relative compressive modulus. The CFD analysis revealed that the structures with the simple and straight pores (e.g., Cube) have higher permeability than the structures with the complex pores (e.g., Fischer-Koch S). The main contribution of the present study is that the relationship between scaffold properties and the underlying microstructure is systematically investigated and thus some guidelines on the design of bone scaffolds are provided, for example, in the scenario where a high surface-to-volume ratio is required, it is suggested to use the Fischer-Koch S based scaffold.

Phosphogypsum (PG) treatment is one of the research hotspots in the field of environmental protection. Many researchers both at home and abroad have devoted themselves to studies on harmless resource treatment of PG, but the treatment technology is unable to meet the demand of PG consumption due to the huge production and storage demands. In order to solve the problem of PG pollution, this study explored the different solidified effects of various modification formulations on the hazardous components in PG, using industrial solid waste calcium carbide slag (CCS) as an alkaline regulator; Portland cement (PC), polyaluminum chloride (PAC) and CaCl2 as the main raw materials of the solidification and stabilization formula and the water content in PG as the reaction medium. The results showed that CCS (0.5%), PC (0.4%) and PAC (0.3%) had a more significant solidified effect on phosphorus (P) and fluoride (F). PAC was added in two steps and reacted under normal temperature and pressure, and its leaching toxicity meets the requirements of relevant standards, which laid an excellent foundation for PG-based ecological restoration materials and filling materials, with low economic cost, simple process and strong feasibility. This will provide great convenience for the later mining and metallurgy.

The components in traditional human–machine interaction (HMI) systems are relatively independent, distributed and low-integrated, and the wearing experience is poor when the system adopts wearable electronics for intelligent control. The continuous and stable operation of every part always poses challenges for energy supply. In this work, a triboelectric technology-based all-in-one self-powered HMI system for wireless remote telemetry and the control of intelligent cars is proposed. The dual-network crosslinking hydrogel was synthesized and wrapped with functional layers to fabricate a stretchable fibrous triboelectric nanogenerator (SF-TENG) and a supercapacitor (SF-SC), respectively. A self-charging power unit containing woven SF-TENGs, SF-SCs, and a power management circuit was exploited to harvest mechanical energy from the human body and provided power for the whole system. A smart glove designed with five SF-TENGs on the dorsum of five fingers acts as a gesture sensor to generate signal permutations. The signals were processed by the microcontroller and then wirelessly transmitted to the intelligent car for remote telemetry and control. This work is of paramount potential for the application of various terminal devices in self-powered HMI systems with high integration for wearable electronics.

Abstract The main objective of this paper is to investigate the dynamic bifurcation for the granulation convection in the solar photosphere. Based on the dynamic bifurcation theory, which is established by Ma and Wang (Phase transition dynamics, pp. 380-459, 2014), the critical parameters ( R , F ) $(R,F)$ condition for the granulation convection is derived. Furthermore, the corresponding R-F-phase diagram is generated. In addition, the bifurcation solution is also obtained with certain assumptions.