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Abstract Background This study explored the correlation between peripheral blood lipid levels and clinicopathological parameters in patients with advanced gastric cancer (GC), focusing on changes in lipid levels during disease progression. Methods Pathological features and serum lipid profiles of 179 patients with stage III-IV gastric adenocarcinoma were analyzed. Lipid parameters examined included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), apolipoprotein AI (Apo AI), apolipoprotein B (Apo B), lipoprotein(a) (Lp(a)), among others. The total cholesterol-lymphocyte score (TL score) and BMI were also calculated. The association between lipid parameters and clinicopathological characteristics such as age, gender, family history, and metastasis sites was assessed. Results In GC patients, females had higher TG levels than males. Patients with peritoneal metastasis had significantly lower levels of TC, LDL-C, Apo B, and B/A ratio. Those with lung metastasis exhibited higher LDL-C levels and lower levels of VLDL-C. No significant associations were found between lipid levels and metastasis to distant lymph nodes, liver, or bone. Female patients with ovarian metastasis had significantly lower VLDL-C levels. Multivariate analysis revealed low TC as an independent risk factor for peritoneal metastasis, high LDL-C and low VLDL-C levels for lung metastasis, and younger age and low VLDL-C for ovarian metastasis. Conclusion Specific blood lipid levels are significantly associated with metastatic sites in advanced gastric cancer. Lipid profiles could serve as potential biomarkers for predicting metastatic sites in GC patients.

Abstract Perineural invasion (PNI) is a new approach of cervical cancer invasion and metastasis, involving the cross-talk between tumor and nerve. However, the initiating signals and cellular interaction mechanisms of PNI remain largely elusive. The nerve-sparing radical hysterectomy (NSRH) proposed to improve postoperative quality of life is only applicable to cervical cancer patients without PNI. Therefore, it is important to elucidate the underlying mechanisms initiating PNI, and suggest the effective biomarkers to predict PNI before NSRH surgery. Here, we found that PNI is the characteristic of advanced cervical cancer, and Schwann cells were the antecedent cells that initiating PNI. Further, neuropeptide neuromedin B (NMB) produced by cervical cancer cells was determined to induce PNI by reprogramming Schwann cells, including driving their morphological and transcriptional changes, promoting their proliferation and migration, and initiating PNI by secreting CCL2 and directing axon regeneration. Mechanistically, cervical cancer cells-produced NMB activated its receptor NMBR in Schwann cells, and opened the T-type calcium channels to stimulate Ca2+ influx through PKA signaling, which could be blocked by the inhibitor. Clinically, combined examination of serum NMB and CCL2 levels was suggested to effectively predict PNI in cervical cancer patients. Our data demonstrate that cervical cancer-produced NMB initiates the reprograming of Schwann cells, which then direct axon regeneration, thus causing PNI onset. The elevated serum NMB and CCL2 levels may be useful for the decision-making to nerve sparing during hysterectomy surgery of cervical cancer patients.

Abstract Background We aimed to evaluate changes in ovarian reserve and quality of life in women treated with ultrasound-guided high-intensity focused ultrasound (USgHIFU) for uterine fibroids. Methods In this single-center prospective study, a total of 69 patients with uterine fibroids treated with USgHIFU from October 2018 to November 2021 were enrolled. Fibroid volume, anti-Müllerian hormone (AMH) levels, uterine fibroid symptom scores, and uterine fibroid symptoms and quality of life (UFS-QOL) questionnaire scores before and 1, 3, and 6 months after USgHIFU treatment were analyzed. Correlations between AMH levels and age, fibroid type, and fibroid location were assessed. Results Data from 54 of the 69 patients included in the present study were analyzed. The UFS-QOL scores at baseline and at 1 month and 6 months after USgHIFU treatment were 70 (50.75–87.50), 57 (44.75–80.00), and 52 (40.75–69.00) points, respectively (p 0.99). The median AMH levels before and at 1, 3 and 6 months after treatment were 1.22 (0.16–3.28) ng/ml, 1.12 (0.18–2.52) ng/ml, 1.15 (0.19–2.08) ng/ml and 1.18 (0.36–2.43) ng/ml, respectively (p = 0.2). Multivariate linear regression analyses revealed that age was independently associated with AMH levels. Conclusions USgHIFU treatment for uterine fibroids can significantly improve quality of life with minimal adverse effects on ovarian function.

Abstract The impact of climate risk on economic and financial fields has attracted considerable interest from academics and practitioners. Recent literature documents that climate risk can affect oil volatility through the dual channel of economic activities and financial markets. Inspired by this, this paper uses climate policy uncertainty (CPU) to examine the predictability of crude oil price volatility. The empirical results indicate that changes in the CPU, rather than the original CPU, can forecast oil volatility. The revealed volatility predictability is both in-sample and out-of-sample. Asset allocation exercise shows that this finding is also economically significant. Furthermore, the predictive ability is mainly concentrated during economic expansions and the CPU contains climate risk that is not available for other predictors. Finally, CPU change indicators can explain the changes in crude oil consumption, which is the economic source of their predictive power.

This study aims at developing a dataset for determining the presence of carotid artery plaques in ultrasound images, composed of 1761 ultrasound images from 1165 participants. A deep learning architecture that combines bilinear convolutional neural networks with residual neural networks, known as the single-input BCNN-ResNet model, was utilized to aid clinical doctors in diagnosing plaques using carotid ultrasound images. Following training, internal validation, and external validation, the model yielded an ROC AUC of 0.99 (95% confidence interval: 0.91 to 0.84) in internal validation and 0.95 (95% confidence interval: 0.96 to 0.94) in external validation, surpassing the ResNet-34 network model, which achieved an AUC of 0.98 (95% confidence interval: 0.99 to 0.95) in internal validation and 0.94 (95% confidence interval: 0.95 to 0.92) in external validation. Consequently, the single-input BCNN-ResNet network model has shown remarkable diagnostic capabilities and offers an innovative solution for the automatic detection of carotid artery plaques.

Lancang County is located in the longitudinal tectonic zone of western Yunnan, where landslides are frequently developed by strong tectonic movement and increasing human activities, thus posing a significant threat to the safety and security of the local population. Therefore, it is of great significance to assess the landslide risk in this area. To construct a landslide risk evaluation index system, data on previous landslides in Lancang County was analyzed, and eight control factors were selected, including elevation, slope, slope direction, stratigraphic lithology, distance from fault, vegetation coverage, distance from road and rainfall. By using the entropy weight method and information coupling value model, the landslide risk in the study area was qualitatively and quantitatively evaluated, and ArcGIS geospatial analysis was used to partition the results. According to the assessment, high-risk areas accounted for 17.91% of the total area, relatively high-risk areas accounted for 37.91%, moderate-risk areas accounted for 25.94%, and low-risk areas accounted for 18.25%.The evaluation results were deemed reasonable, and the entropy weight method and information coupling value model were found to be appropriate for landslide hazard assessment in the region.

Abstract Background Elucidating the mechanism of fiber transformation underlying microbial metabolism is critical for improving fiber-rich silage digestibility and preserving silage energy for ruminant nutrient absorption. However, few studies have combined quantitative microbial function and transformation products in silage to explain this mechanism. Here, we constructed a workflow to detect the substrates and products of fiber transformation in mixed silage of Sesbania cannabina and sweet sorghum (SS) and combined the absolute quantification 16S rRNA sequencing to reveal this mechanism. Results The synergistic effect of Lactobacillus cocktail and cellulase (LC) simplified the microbial diversity and minimized the microbial quantity, making Lentilactobacillus buchneri the dominant species in SS silage. As a result, the LC-treated silage had greater lactic acid content, lower pH value, and less NH3-N content. The indigestible fibers were significantly decreased due to the synergistic effect of the Lactobacillus cocktail and cellulase. Changes in microbial structure during ensiling also resulted in metabolic alterations. The increased levels of microbial enzymes, including β-glucosidase and sucrose phosphorylase, involved in starch and sucrose metabolism led to the enrichment of monosaccharides (including glucose, xylose, mannose, galactose, ribose, rhamnose, and arabinose) in the LC-treated silage. We found that L. buchneri was positively associated with β-glucosidase and sucrose phosphorylase, reflecting the crucial contribution of L. buchneri to fiber decomposition in SS silage. Conclusion Using an absolute quantitative microbiome, we found that LC treatment decreased the microbial biomass in SS silage, which in turn promoted the energy preservation in the SS silage. The cooperative interaction of the Lactobacillus cocktail and cellulase improved the fiber decomposition and in vitro dry matter digestibility rate by changing the microbiome structure and function in the SS silage, providing guidance and support for future fiber-rich silage production in the saline-alkaline region. Graphical Abstract

Endometrial cancer (EC) is one of the most common gynecologic malignancies, which lacking effective drugs for intractable conditions or patients unsuitable for surgeries. Recently, the patient-derived organoids (PDOs) are found feasible for cancer research and drug discoveries. Here, we have successfully established a panel of PDOs from EC and conducted drug repurposing screening and mechanism analysis for cancer treatment. We confirmed that the regulatory β subunit of methionine adenosyltransferase (MAT2B) is highly correlated with malignant progression in endometrial cancer. Through drug screening on PDOs, we identify JX24120, chlorpromazine derivative, as a specific inhibitor for MAT2B, which directly binds to MAT2B (Kd = 4.724 μM) and inhibits the viability of EC PDOs and canonical cell lines. Correspondingly, gene editing assessment demonstrates that JX24120 suppresses tumor growth depending on the presence of MAT2B in vivo and in vitro. Mechanistically, JX24120 induces inhibition of S-adenosylmethionine (SAMe) synthesis, leading to suppressed mTORC1 signaling, abnormal energy metabolism and protein synthesis, and eventually apoptosis. Taken together, our study offers a novel approach for drug discovery and efficacy assessment by using the PDOs models. These findings suggest that JX24120 may be a potent MAT2B inhibitor and will hopefully serve as a prospective compound for endometrial cancer therapy.

ObjectiveThis study explores the benefits of targeted-immunotherapy combination in third-line or beyond treatment for microsatellite stable (MSS) metastatic colorectal cancer (mCRC) in a real-world setting.MethodsPatients with MSS mCRC who were treated with either a targeted-immunotherapy combination or targeted therapy alone in the third-line or beyond setting at our hospital from August 2018 to August 2022 were included in the study. Inclusion criteria comprised patients treated with targeted therapy alone or in combination with immunotherapy. Effectiveness was compared between treatments, and patients with the potential to benefit from targeted-immunotherapy combination were identified.ResultsAmong 71 patients, 31 received targeted therapies alone (TT group) and 40 received a combination of targeted therapy and immunotherapy (TI group). The TI group had higher objective response rates (20% vs 3.2%) and disease control rates (82.5% vs 58.1%). The median progression-free survival was significantly better in the TI group (4.6 vs 4.1 months, P = 0.027). Liver metastasis was associated with poor prognosis, while patients with only lung metastases had the longest median progression-free survival of 12.3 months with combination therapy.ConclusionThe study indicates that targeted-immunotherapy combination offers more benefits than targeted therapy alone for MSS mCRC in the third-line or beyond setting.

Soil microbial inoculants are widely recognized as an environmentally friendly strategy for promoting crop growth and increasing productivity. However, research on utilizing the microbial resources from desert biological soil crusts to enhance crop growth remains relatively unexplored. In the present work, a bacterial strain designated AC1-8 with high levels of amylase, protease, and cellulase activity was isolated from cyanobacterial crusts of the Tengger Desert and identified as Bacillus cereus (CGMCC 1.60196). The refinement of the fermentation parameters of B. cereus CGMCC 1.60196 determined that the most effective medium for biomass production was composed of 5 g/L glucose, 22 g/L yeast extract and 15 g/L MgSO4, and the optimal culture conditions were pH 6.0, temperature 37°C, inoculation quantity 3% and agitation speed 240 rpm. Furthermore, the utilization of B. cereus CGMCC 1.60196 has resulted in substantial improvements in various growth parameters of maize seedlings, including shoot length, shoot fresh and dry weights, root fresh and dry weights, and the contents of chlorophyll a, chlorophyll b, and total chlorophyll. The most pronounced growth promotion was observed at an application concentration of 1 × 109 CFU/m2. These results suggest that the novel B. cereus strain, isolated from cyanobacterial crusts, can be regarded as an exemplary biological agent for soil improvement, capable of enhancing soil conditions, promoting crop cultivation and supporting food production.

Background: Immune checkpoint inhibitors (ICIs), especially anti-PD-1/PD-L1 antibodies, have emerged as promising therapeutic options for cervical cancer. However, the efficacy of anti-PD-1 antibody monotherapy is limited. Cryoablation could elicit an anti-tumor immune response, thereby presenting itself as a potential approach to augment the response of ICIs. The aim of our study was to investigate the systemic immunological effects of cryoablation and the potential synergistic anti-tumor effects of cryoablation and anti-PD-1 antibody in cervical cancer. Methods: We established U14 murine bilateral subcutaneous cervical cancer model, wherein the primary tumors were treated with cryoablation. Flow cytometry, immunohistochemistry and RNA-seq were used to analyze the immune cell infiltration and immune-associated pathways in the secondary tumor. Results: Our study revealed that cryoablation reprogrammed the immune landscape, leading to an enhanced infiltration of CD8+ T cell in distant tumors. Cryoablation created a conducive environment for increasing the efficacy of anti-PD-1 immunotherapy. Cryoablation in combination with anti-PD-1 antibody inhibited distant tumors growth and improved mouse survival. Mechanistically, this combination therapy could augment the infiltration of CD8+ T cells, CD4+ T cells, dendritic cells and M1-like tumor-associated macrophages, enhance multiple aspects of antitumor immune response, and reduce immunosuppressive cells such as M2-like tumor-associated macrophages and myeloid-derived suppressor cells in distant tumors. Conclusions: Combination therapy with cryoablation and anti-PD-1 antibody induces an effective abscopal effect in murine model of cervical cancer and may be a novel therapeutic approach for patients with advanced/recurrent cervical cancer.

Abstract The traditional flood hazard assessment system for emergency departments is based on the average hazard index of administrative regions. However, this approach may overlook errors with significant hazards caused by the transition from watershed hazard maps to administrative hazard maps. In our study, we propose an innovative approach that utilizes fuzzy sets to represent flood risk grades, incorporating the upper and lower boundaries of membership variety to effectively indicate higher and lower risks errors, respectively. The introduction of fuzzy set risk grades not only incorporates conventional information but also addresses local risk errors caused by the conversion, enabling Emergency Departments to allocate disaster prevention funds accurately for all risk spots. The fund allocation coefficient, based on fuzzy risk grades, strongly correlates with the proportion of flood‐affected populations over time, highlighting the robustness of utilizing fuzzy set risk grades.

BackgroundAbout 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent low-grade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV.MethodsIn this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed.ResultsTotally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log10 IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, p < 0.001), HBV DNA ≥ 6.0 Log10 IU/mL (OR = 1.370, 95% CI: 1.054-1.780, p = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, p < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, P = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, p = 0.002), and PLT < 100×109/L (OR = 1.450, 95% CI: 1.094-1.922, p = 0.010) at baseline were related to the development of LLV.ConclusionsHigh HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment.

ObjectiveThis study aimed to investigate the causal relationship between gut microbiota characteristics (207 taxa and 205 pathways) and Alzheimer’s disease and determine and quantify the role of immune cells as potential mediators.MethodsGut microbiota characteristics (207 taxa and 205 pathways) were obtained from the NHGRI-EBI GWAS Catalog project, while Alzheimer’s disease data and 731 immune cell characteristics were obtained from the IEU Open GWAS project. Two-sample Mendelian randomization (MR) was conducted to determine whether gut microbiota characteristics (207 taxa and 205 pathways) were causally related to Alzheimer’s disease. Furthermore, two-step MR was employed to quantify the proportion of the effect of immune cell characteristics mediated by gut microbiota characteristics (207 taxa and 205 pathways) on Alzheimer’s disease.ResultsA total of 17 immune cell characteristics were identified as potential mediators for 13 gut microbiota influencing Alzheimer’s disease, with Effector Memory CD4+ T-cell Absolute Count accounted for 8.99% of the causal relationship between genus Oscillibacter and Alzheimer’s disease.ConclusionIn summary, our research confirms a causal relationship between gut microbiota and Alzheimer’s disease, with immune cells contributing to a significant portion of the effect. However, the full mediators of gut microbiota’s impact on Alzheimer’s disease remain unclear. Further investigation is warranted to explore additional potential risk factors acting as mediators.

ABSTRACT The cAMP receptor proteins (CRPs) play a critical role in bacterial environmental adaptation by regulating global gene expression levels via cAMP binding. Here, we report the structure of DdrI, a CRP family protein from Deinococcus radiodurans. Combined with biochemical, kinetic, and molecular dynamics simulations analyses, our results indicate that DdrI adopts a DNA-binding conformation in the absence of cAMP and can form stable complexes with the target DNA sequence of classical CRPs. Further analysis revealed that the high-affinity cAMP binding pocket of DdrI is partially filled with Tyr113-Arg55-Glu65 sidechains, mimicking the anti-cAMP-mediated allosteric transition. Moreover, the second syn-cAMP binding site of DdrI at the protein-DNA interface is more negatively charged compared to that of classical CRPs, and manganese ions can enhance its DNA binding affinity. DdrI can also bind to a target sequence that mimics another transcription factor, DdrO, suggesting potential cross-talk between these two transcription factors. These findings reveal a class of CRPs that are independent of cAMP activation and provide valuable insights into the environmental adaptation mechanisms of D. radiodurans.IMPORTANCEBacteria need to respond to environmental changes at the gene transcriptional level, which is critical for their evolution, virulence, and industrial applications. The cAMP receptor protein (CRP) of Escherichia coli (ecCRP) senses changes in intracellular cAMP levels and is a classic example of allosteric effects in textbooks. However, the structures and biochemical activities of CRPs are not generally conserved and there exist different mechanisms. In this study, we found that the proposed CRP from Deinococcus radiodurans, DdrI, exhibited DNA binding ability independent of cAMP binding and adopted an apo structure resembling the activated CRP. Manganese can enhance the DNA binding of DdrI while allowing some degree of freedom for its target sequence. These results suggest that CRPs can evolve to become a class of cAMP-independent global regulators, enabling bacteria to adapt to different environments according to their characteristics. The first-discovered CRP family member, ecCRP (or CAP) may well not be typical of the family and be very different to the ancestral CRP-family transcription factor.

NUAK2 is a member of the AMP-activated protein kinase (AMPK) family, which plays an essential role in cellular processes such as apoptosis, proliferation, and cell fate. Recent studies have already shown that silencing of NUAK2 blocks proliferation and promotes apoptosis of human melanoma cells and liver cancer cells. In addition, NUAK2 is involved in the development of glioblastoma via regulating the expression of cancer stem cell-related genes, and it promotes the cell cycle entry in the glioblastoma cells. However, the expression and the role of NUAK2 in the progress of peripheral nerve regeneration after injury are yet to be elucidated. We observed that NUAK2 was upregulated following distal sciatic nerve crush (SNC). Interestingly, we discovered that NUAK2 showed co-localization with S100 (Schwann cell marker). Furthermore, we found that the NUAK2 had a spatiotemporal protein expression, which was consistent with proliferating cell nuclear-antigen (PCNA). The protein level of NUAK2 and YAP was upregulated in the model of TNF-α-induced Schwann cell (SC) proliferation. Furthermore, flow cytometry analysis, CCK-8, transwell assays, and wound healing assays were all performed with the purpose of exploring the role of NUAK2 in the regulation of SC proliferation and migration. More importantly, we found that NUAK2-deficient SCs showed significantly reduced expression of Yes-associated protein (YAP). Bioinformatic analysis identified upstream regulators of NUAK2 and NUAK2-associated genes (e.g., YAP1). Finally, we investigated the recovery changes during regeneration progress through the walking track analysis. Thus, we speculated that NUAK2 was involved in biochemical and physiological responses of SCs after SNC via YAP-driven proliferation and migration, and this study determined the importance of NUAK2 as a potential target in peripheral nerve regeneration.

BackgroundCarotid plaques are major risk factors for stroke. Carotid ultrasound can help to assess the risk and incidence rate of stroke. However, large-scale carotid artery screening is time-consuming and laborious, the diagnostic results inevitably involve the subjectivity of the diagnostician to a certain extent. Deep learning demonstrates the ability to solve the aforementioned challenges. Thus, we attempted to develop an automated algorithm to provide a more consistent and objective diagnostic method and to identify the presence and stability of carotid plaques using deep learning.MethodsA total of 3,860 ultrasound images from 1,339 participants who underwent carotid plaque assessment between January 2021 and March 2023 at the Shanghai Eighth People’s Hospital were divided into a 4:1 ratio for training and internal testing. The external test included 1,564 ultrasound images from 674 participants who underwent carotid plaque assessment between January 2022 and May 2023 at Xinhua Hospital affiliated with Dalian University. Deep learning algorithms, based on the fusion of a bilinear convolutional neural network with a residual neural network (BCNN-ResNet), were used for modeling to detect carotid plaques and assess plaque stability. We chose AUC as the main evaluation index, along with accuracy, sensitivity, and specificity as auxiliary evaluation indices.ResultsModeling for detecting carotid plaques involved training and internal testing on 1,291 ultrasound images, with 617 images showing plaques and 674 without plaques. The external test comprised 470 ultrasound images, including 321 images with plaques and 149 without. Modeling for assessing plaque stability involved training and internal testing on 764 ultrasound images, consisting of 494 images with unstable plaques and 270 with stable plaques. The external test was composed of 279 ultrasound images, including 197 images with unstable plaques and 82 with stable plaques. For the task of identifying the presence of carotid plaques, our model achieved an AUC of 0.989 (95% CI: 0.840, 0.998) with a sensitivity of 93.2% and a specificity of 99.21% on the internal test. On the external test, the AUC was 0.951 (95% CI: 0.962, 0.939) with a sensitivity of 95.3% and a specificity of 82.24%. For the task of identifying the stability of carotid plaques, our model achieved an AUC of 0.896 (95% CI: 0.865, 0.922) on the internal test with a sensitivity of 81.63% and a specificity of 87.27%. On the external test, the AUC was 0.854 (95% CI: 0.889, 0.830) with a sensitivity of 68.52% and a specificity of 89.49%.ConclusionDeep learning using BCNN-ResNet algorithms based on routine ultrasound images could be useful for detecting carotid plaques and assessing plaque instability.

Abstract Background Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women. Methods A total of 3251 hrHPV-positive women aged 30–82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated. Results CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 −) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%). Conclusions PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals. Trial registration ChiCTR2100048972. Registered on 19 July 2021.

Different porous structures were studied through finite element analysis and then optimal porous structure was selected for the orthopedic applications. The optimal Voronoi structure was designed and fabricated using 3D printing. The mechanical properties and osseointegration ability were both investigated. The mechanical tests showed that the tensile strength, compressive strength and bending strength of Voronoi structures were obviously higher than that of the human bone, and the modulus of Voronoi structures were similar to human bone. In addition, the animal experimental results exhibited that obvious bone ingrowth was found from Month 1 to Month 6. This study provides some theoretical references for the orthopedic application of porous structures.

Abstract Background The primary purpose of this study was to investigate the predictive value of alterations in cervical artery hemodynamic parameters induced by a simulated end-inspiratory occlusion test (sEIOT) measured by ultrasound for predicting postinduction hypotension (PIH) during general anesthesia. Methods Patients undergoing gastrointestinal tumor resection under general anesthesia were selected for this study. Ultrasound has been utilized to assess hemodynamic parameters in carotid artery blood flow before induction, specifically focusing on variations in corrected flow time (ΔFTc) and peak blood flow velocity (ΔCDPV), both before and after sEIOT. Anesthesia was induced by midazolam, sufentanil, propofol, and rocuronium, and blood pressure (BP) and heart rate (HR) were recorded within the first 10 min following endotracheal intubation. PIH was defined as fall in systolic blood pressure (SBP) or mean arterial pressure (MAP) by > 30% of baseline or MAP to

Poultry semen cryopreservation technology is one of the most direct methods to protect poultry germplasm, and in this study, the back and abdomen massage method is used to collect the semen of 20 Huoyan male geese, which is on the basis of EK diluent adding different combinations of dimethyl sulfoxide (DMSO) and trehalose, in total 7 different combinations treatments were achieved: D1T0 (5%DMSO), D1T1 (5% DMSO + 50 mM trehalose), D1T2 (5%DMSO + 100 mM trehalose), D2T0 (10% DMSO), D2T1 (10% DMSO + 50 mM trehalose), D2T2 (10% DMSO + 100 mol trehalose) and no addition group D0T0 (0% DMSO + 0 mM trehalose). Diluted semen was frozen in granules in liquid nitrogen vapour. After thawing in 40°C water bath, determinate sperm livability, acrosome integrity, plasma membrane integrity, catalase (CAT) activity, superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, malondialdehyde (MDA) content and reactive oxygen species (ROS) level, and the results showed that 10% DMSO and 0.05 mol/L trehalose could significantly improve the sperm motility, acrosome integrity rate and plasma membrane integrity rate after thawing, and significantly increase the levels of antioxidant enzymes CAT, SOD and GSH-Px in seminal plasma (P

This paper investigates the motion state estimation problem of the unmanned surface vehicle (USV) steering system in wireless sensor networks based on the binary coding scheme (BCS). In response to the presence of bandwidth constraints and mixed cyber-attacks in USV communication networks, this paper proposes an improved set-membership state estimation algorithm based on BCS. This algorithm partially addresses the problem of degraded performance in USV steering motion state estimation caused by mixed cyber-attacks and bandwidth constraints. Furthermore, this paper proposes a robust resilient filtering framework considering the possible occurrence of unknown but bounded (UBB) noises, model parameter uncertainties, and estimator gain perturbations in practical scenarios. The proposed framework can accurately estimate the sway velocity, yaw velocity, and roll velocity of the USV under the concurrent presence situation of mixed cyber-attacks, communication capacity constraints, UBB noises, model parameter uncertainties, and estimator gain perturbations. This paper first utilizes mathematical induction to provide the sufficient conditions for the existence of the desired estimator, and obtains the estimator gain by solving a set of linear matrix inequalities. Then, a recursive optimization algorithm is utilized to achieve optimal estimation performance. Finally, the effectiveness of the proposed estimation algorithm is verified through a simulation experiment.

Based on 40 years of routine water quality monitoring data from Shenzhen Bay and special intensive monitoring since 2021, we analysed the spatiotemporal variations in nitrogen and phosphorus pollution. The results indicate serious levels of nitrogen and phosphorus pollution in Shenzhen Bay. Although recent trends show a decline in concentrations of inorganic nitrogen and reactive phosphate—with the annual average concentration of inorganic nitrogen dropping below 1.0 mg/L since 2020 and reactive phosphate levels near the bay mouth decreasing to approximately 0.020 mg/L—the overall water quality still does not meet China’s Class IV seawater quality standards. Additionally, water quality is poorer during the rainy season, with the average summer concentration of inorganic nitrogen being over 25% higher than in spring and autumn. The water quality is primarily influenced by land-sourced pollutants and tidal effects, generally, with the concentration of DIN and DIP decreased from the estuary of the Shenzhen River, the main seagoing river, to the bay mouth. Near the river’s mouth, concentrations of inorganic nitrogen and reactive phosphate are approximately six and four times higher, respectively, than those near the bay mouth. Due to current emission standards and sewage disposal methods, the proportion of nitrate nitrogen in DIN has significantly increased, exceeding 80% since 2020. To improve the water quality of Shenzhen Bay and to reduce pollution inputs, coordinated land and marine development activities are recommended.

Purpose: This study aimed to compare the effects of the phytoestrogens resveratrol (RES) and genistein (GEN) on the contractility of isolated uterine smooth muscle from rats, focusing on both spontaneous and stimulated contractions, and to investigate the underlying mechanisms. Methods: Uterine strips were suspended vertically in perfusion chambers containing Kreb’s solution, various concentrations of RES and GEN were added to the ex vivo uterine strips, and contractions were measured before and after incubation with RES or GEN. Results: (1) Both RES and GEN inhibited K+-induced contractions in a dose-dependent manner; the β/β2-adrenoceptor antagonist propranolol (PRO), ICI118551, the ATP-dependent K+ channel blocker glibenclamide (HB-419) and the NO synthase inhibitor N-nitro-L-arginine (L-NNA) diminished the inhibitory effects of RES and GEN on K+-induced contractions. (2) RES and GEN also dose-dependently inhibited PGF2α-induced uterine contractions. (3) The inhibitory effects of RES and GEN were observed in spontaneous contractile activities as well; PRO, ICI118551, HB-419 and L-NNA attenuated the inhibitory effects of RES and GEN on the spontaneous contractions of isolated uterine muscle strips. (4) RES and GEN significantly decreased the cumulative concentration response of Ca2+ and shifted the Ca2+ cumulative concentration–response curves to the right in high-K+ Ca2+-free Kreb’s solution. (5) RES and GEN markedly reduced the first phasic contraction induced by oxytocin, acetylcholine, and prostaglandin F2α but did not alter the second phasic contraction caused by CaCl2 in Ca2+-free Kreb’s solution. Conclusions: RES and GEN can directly inhibit both spontaneous and activated contractions of isolated uterine smooth muscle. The mechanisms underlying the inhibitory effects of RES and GEN likely involve β adrenergic receptor activation, reduced Ca2+ influx and release, the activation of ATP-dependent K+ channels and increased NO production.

One of the primary factors in the hydrological cycle is reference evapotranspiration (ET0). The prediction of ET0 is crucial to manage irrigation water in agriculture under climate change; however, little research has been conducted on the trends of ET0 changes in Shandong Province. In this study, to estimate ET0 in the entire Shandong Province, 245 sites were chosen, and the monthly ET0 values during 1901–2020 were computed using the Hargreaves–Samani formula. A deep learning model, termed SAO-CNN-BiGRU-Attention, was utilized to forecast the monthly ET0 during 2021–2100, and the predictions were compared to two CMIP6 climate scenarios, SSP2-4.5 and SSP5-8.5. The hierarchical clustering results revealed that Shandong Province encompassed three homogeneous regions. The ET0 values of Clusters H1 and H2, which were situated in inland regions and major agricultural areas, were the highest. The SAO-CNN-BiGRU-Attention and SSP5-8.5 forecasting results generally displayed a monotonically growing trend during the forecast period in the three regions; however, the SAO-CNN-BiGRU-Attention model displayed a declining tendency at a few points. According to the SAO-CNN-BiGRU-Attention and SSP5-8.5 results, during 2091–2100, H1, H2, and H3 will reach their peaks; the SSP2-4.5 results show that H1, H2, and H3 will peak in 2031–2040. At the end of the forecast period, for Clusters H1, H2, and H3, the prediction rate of SAO-CNN-BiGRU-Attention increased by 1.31, 1.56%, and 1.80%, respectively, whereas SSP2-4.5’s prediction rate increased by 0.31%, 0.95%, and 1.57%, respectively, and SSP5-8.5’s prediction rate increased by 10.88%, 10.76%, and 10.69%, respectively. The prediction results of SAO-CNN-BiGRU-Attention were similar to those of SSP2-4.5 (R2 > 0.96). The SAO-CNN-BiGRU-Attention deep learning model can be used to forecast future ET0.

IntroductionThere is a lack of research on the current level of diabetes knowledge and health information-seeking behaviors among patients with diabetes in rural areas of China’s economically underdeveloped regions during COVID-19, as well as a lack of up-to-date evidence on glycemic control and the incidence of complications among rural patients with diabetes.ObjectivesTo investigate the prevalence of glycemic control and complications among patients with diabetes in rural areas, to explore the current status and correlation of diabetes knowledge level and health information-seeking behavior, and to analyze the factors affecting diabetes knowledge level.MethodsFrom January 2022 to July 2022, we conducted a screening on diabetic complications and a questionnaire survey among 2,178 patients with diabetes in 15 county hospitals in rural areas of Guangxi Zhuang Autonomous Region. The patients’ knowledge level and health information-seeking behavior were investigated. Spearman correlation analysis was used to assess the correlation between diabetes knowledge and health information-seeking behavior. Multiple linear regression analysis was used to test how demographic information and health information-seeking behavior influenced the level of diabetes knowledge.ResultsOf 2,178 patients with diabetes in rural areas, 1,684 (77.32%) had poor glycemic control, and the prevalence of diabetic complications was estimated to be 72.13%. Patients with diabetes had poor diabetes knowledge and health information-seeking behavior, and there is a strong positive correlation between them. Diabetes knowledge level was influenced by per capita household disposable income, occupational status, gender, age, ethnicity, family history of diabetes, insulin use, glycated hemoglobin, education level, number of complications and health information-seeking behavior.ConclusionPatients with diabetes in rural areas have poor glycemic control and a high incidence of diabetic complications. Patients with diabetes in rural areas have poor knowledge and inadequate health information-seeking behavior. Systematic and standardized education should be provided to improve patients’ diabetes knowledge and thus improve their self-management ability.

The vaccine-induced innate immune response is essential for the generation of an antibody response. To date, how Ad5-vectored vaccines are influenced by preexisting anti-Ad5 antibodies during activation of the early immune response remains unclear. Here, we investigated the specific alterations in GP1,2-specific IgG-related elements of the early immune response at the genetic, molecular, and cellular levels on days 0, 1, 3, and 7 after Ad5-EBOV vaccination. In a causal multiomics analysis, distinct early immune responses associated with GP1,2-specific IgG were observed in Ad5-EBOV recipients with a low level of preexisting anti-Ad5 antibodies. This study revealed the correlates of the Ad5-EBOV-induced IgG response and provided mechanistic evidence for overcoming preexisting Ad5 immunity during the administration of Ad5-vectored vaccines.

Abstract Tumors often overexpress glucose‐regulated proteins, and agents that interfere with the production or activity of these proteins may represent novel cancer treatments. The chlorpromazine derivative JX57 exhibits promising effects against endometrial cancer with minimal extrapyramidal side effects; however, its mechanisms of action are currently unknown. Here, glucose‐regulated protein 75 kD (GRP75) is identified as a direct target of JX57 using activity‐based protein profiling and loss‐of‐function experiments. The findings show that GRP75 is necessary for the biological activity of JX57, as JX57 exhibits moderate anticancer properties in GRP75‐deficient cancer cells, both in vitro and in vivo. High GRP75 expression is correlated with poor differentiation and poor survival in patients with endometrial cancer, whereas the knockdown of GRP75 can significantly suppress tumor growth. Mechanistically, the direct binding of JX57 to GRP75 impairs the structure of the mitochondria‐associated endoplasmic reticulum membrane and disrupts the endoplasmic reticulum–mitochondrial calcium homeostasis, resulting in a mitochondrial energy crisis and AMP‐activated protein kinase activation. Taken together, these findings highlight GRP75 as a potential prognostic biomarker and direct therapeutic target in endometrial cancer and suggest that the chlorpromazine derivative JX57 can potentially be a new therapeutic option for endometrial cancer.

ABSTRACT: Feather is an important economic trait of poultry, and growth and development state of feathers plays an important role in the economic value of poultry. Dermal fibroblasts are required for structural integrity of the skin and for feather follicle development. How FOXO3 affects feather follicle development as skin tissues change during goose embryo (Anser cygnoides) development and growth is not well understood. Here, we demonstrate that in vitro culture of single feathers and skin tissue results in changes in feather morphological structure by adding drugs to the culture medium that affect FOXO3 expression. We used feather follicles to show that during growth, the root location of feathers, the dermis layer, affects cell proliferation and apoptosis and regulates the expression of major genes in the Wingless-types/beta-catenin (Wnt/β-catenin) signaling pathway through the activity of FOXO3 in dermal fibroblasts. Feathers and dorsal skin tissues develop the correct structure, but feather length and width and feather follicle diameter change significantly (p < 0.05) without significant changes in feather follicle density (p > 0.05). Transfected dermal fibroblasts also showed that FOXO3 affected the formation and development of feather follicles in the embryonic stage by regulating the Wnt/β-catenin signaling pathway. Therefore, this study reveals the critical role of dermal fibroblast-FOXO3-induced Wnt/β-catenin signaling in promoting the formation and development of embryonic feather follicles.

Microplastics (MPs) weather after entering the environment gradually, and the interaction with metal ions in the aqueous environment has received extensive attention. However, there are few studies on Hg(Ⅱ), especially the effect of MPs on the release of Hg0(DEM) in water after entering the aqueous environment. In this study, four types of MPs (PP, PE, PET, PVC) were selected to study the adsorption and desorption behavior of Hg(Ⅱ) after photoaging and to explore the influence of MPs on the release of DEM in seawater under different lighting conditions. The results showed that the specific surface area, negative charges, and oxygen-containing functional group of MPs increased after aging. The adsorption capacity of aged MPs for Hg(Ⅱ) was significantly improved, which was consistent with the pseudo-first-order and pseudo-second-order model, indicating that the adsorption process was a chemical and physical adsorption. The fitting results of the in-particle diffusion model indicated that the adsorption was controlled by multiple steps. Hg(Ⅱ) was easier to desorb in the simulated gastric fluid environment. Because the aged MPs had the stronger binding force to Hg(Ⅱ), their desorption rate is lower than new MPs. Under visible light and UVA irradiation, MPs inhibited the release of Hg0. Under UVA, the mass of DEM produced in seawater with aged PE and PVC was higher than that of new PE and PVC. The aged PE and PVC could produce more ·O2-, which was conducive to the reduction of mercury. However, in UVB irradiation, the addition of MPs promoted the release of DEM, and ·O2- also played an important contribution in affecting the photochemical reaction of mercury. Therefore, the presence of aged MPs will significantly affect the water-air exchange of Hg in water. Compared with new MPs, aged MPs improved the contribution of free radicals in Hg transformation by releasing reactive oxygen species. This study extends the understanding of the effects of MPs on the geochemical cycle of Hg(Ⅱ) in seawater, better assesses the potential combined ecological risks of MPs and Hg(Ⅱ), and provides certain guidance for the pollution prevention and control of MPs.

Abstract Rift Valley fever virus (RVFV) is listed as a priority pathogen by the World Health Organization (WHO) because it causes serious and fatal disease in humans, and there are currently no effective countermeasures. Therefore, it is urgent to develop a safe and efficacious vaccine. Here, we developed six nucleotide-modified mRNA vaccines encoding different regions of the Gn and Gc proteins of RVFV encapsulated in lipid nanoparticles, compared their ability to induce immune responses in mice and found that mRNA vaccine encoding the full-length Gn and Gc proteins had the strongest ability to induce cellular and humoral immune responses. IFNAR(−/−) mice vaccinated with mRNA-GnGc were protected from lethal RVFV challenge. In addition, mRNA-GnGc induced high levels of neutralizing antibodies and cellular responses in rhesus macaques, as well as antigen-specific memory B cells. These data demonstrated that mRNA-GnGc is a potent and promising vaccine candidate for RVFV.

Abstract Satellites can “sense” oil inventory, but cloud cover prevents observation, which reduces the flow of information into the oil market and creates uncertainty about information availability. The effects of the availability of such information on oil prices need to be thoroughly explored. Therefore, using time-series prediction, this paper examines the effects of the availability of satellite-based information on oil returns. The cloud cover above the floating roof tanks in major oil storage areas is measured to predict oil returns through regression approaches. The empirical results indicate that higher cloudiness in a week leads to lower oil returns in the following week. The predictive ability of cloudiness is significant from both in-sample and out-of-sample perspectives. The ability of cloudiness measures to predict oil returns can be explained by information uncertainty and information flow channels. The findings have important implications for asset pricing and risk management using big data.

Abstract Background Long interspersed nuclear element-1 (LINE-1 or L1) comprises 17% of the human genome. As the only autonomous and active retrotransposons, L1 may take part in cancer initiation and progression in some ways. The studies of L1 in cancer mainly focus on the impact of L1 insertion into the new genome locus. The L1 5´ untranslated region (UTR) also contains antisense promoter (ASP) activity, generating L1-gene chimeric transcripts to a neighbor exon. Some of these ASP-associated genes have been reported to be overexpressed in cancer and promote cancer cell growth. However, little is known about overall expression patterns and the roles of L1 ASP-associated genes in human cancers. Results L1 ASP-associated genes were frequently dysregulated in cancer and associated with the cell cycle, the PI3K/AKT pathway, and the GTPase signaling pathway. The expression of L1 ASP-associated genes was correlated with tumor patient prognosis. Hub L1 ASP-associated genes CENPU and MCM2 showed a correlation with immune infiltration, clinical T stage, and cancer stemness in pan-cancer. Knockdown of L1 ASP-associated gene LINC00491 resulted in a significant decrease in tumor growth and migration ability. Conclusions The expression of L1 ASP-associated genes is significantly dysregulated at the pan-cancer level, which is closely related to the tumor microenvironment, progression, and patient prognosis. Hub genes CENPU and MCM2 are expected to be new tumor diagnostic markers and therapeutic targets.

ABSTRACTThe objective of this study was to investigate the effects of ultrasonically emulsified palm oil (UE-PA), peanut oil (UE-PE), and sunflower oil (UE-SU) on the whiteness, textural, rheological, and microstructural properties of surimi gels from silver carp. Three ultrasonically emulsified oils had different specific fatty acids and oil droplet sizes of 300-400 nm. Compared with the control group, low addition of UE-SU (2.5 g/100 g) showed the highest water-holding capacity (WHC), storage modulus (G’), and hydrogen bond in surimi gels. The low addition of UE-PE (2.5 g/100 g) increased disulfide bond, β-sheet, and β-turn of surimi gel, so had higher hardness and chewiness values, comparing to those with other emulsified oils. As ultrasonically emulsified oil addition increased in surimi gels (2.5–7.5 g/100 g), hardness, chewiness, WHC, G’ were decreased, while whiteness was increased (p

ABSTRACTThe objective of this study was to investigate the effects of aqueous extract of lotus root knot (AELRK) on the gel characteristics of silver carp surimi. Gel strength, storage modulus, and disulfide bond of surimi gels were significantly increased with the addition of the AELRK (p < 0.05), especially at 10% AELRK (p < 0.05), where gel strength and disulfide bond were enhanced by 14.7% and 41.6%, respectively, but decreased in expressible moisture content, ionic bond, hydrogen bond and hydrophobic interaction. Adding 10% AELRK could enhance cross-linking degree surimi gels with the denser and smoother microstructure. There was the reduction in myosin heavy chain but not significant change in actin. More addition of the AELRK significantly decreased in L* and whiteness of surimi gels (p < 0.05) but increased in a * . Therefore, there would be a potential to utilize the phenolic compounds from lotus root to improve the quality of silver carp surimi.

ABSTRACTThe objective of this study was to investigate the effects of various pHs and NaCl concentrations on physicochemical properties of surimi from grass carp during washing. Surimi protein recovery was higher with 0.25% and 0.5% NaCl at the pH 5 or 7 than that with other pHs and NaCl concentrations, while the highest recovery was obtained with 0.25% NaCl at the pH 7. It decreased protein recovery and salt-soluble protein of surimi as NaCl increased by more than 1.0% during washing. The water-soluble protein content was significantly higher at the pH 3 than at other pHs, while the SDS-PAGE of surimi protein exhibited intense sarcoplasmic protein bands at the pH 3. There were significantly fewer hydrophobic groups of actomyosin treated with 0.25% NaCl at the pH 5 or 7 than that with other pHs and NaCl concentrations in washing solution. The α-helix of actomyosin was increased with the increase of NaCl during washing. In general, the washing with 0.25%−0.5% NaCl at the pH 5–7 could significantly increase the yield of surimi from grass carp.

ABSTRACTThe objective of this study was to investigate the effects of okara on the quality of silver carp surimi gels. The characteristics of surimi gels without and with okara (0%, 2%, 4%, 6%, 8%, and 10% w/w) were evaluated by measuring water-holding capacity (WHC), color, sensory, textural, and rheological properties. With further addition of okara, WHC, breaking force, textural properties, and whiteness were decreased (P

Recombinant adenovirus serotype 5 (Ad5) vector has been widely applied in vaccine development targeting infectious diseases, such as Ebola virus disease and coronavirus disease 2019 (COVID-19). However, the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines. Thus, there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors. Herein, we address this need by utilizing biocompatible nanoparticles to modulate Ad5–host interactions. We show that positively charged human serum albumin nanoparticles ((+)HSAnp), which are capable of forming a complex with Ad5, significantly increase the transgene expression of Ad5 in both coxsackievirus–adenovirus receptor-positive and -negative cells. Furthermore, in charge- and dose-dependent manners, Ad5/(+)HSAnp complexes achieve robust (up to 227-fold higher) and long-term (up to 60 days) transgene expression in the lungs of mice following intranasal instillation. Importantly, in the presence of preexisting anti-Ad5 immunity, complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity. These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.

Abstract Forecasting stock returns is challenging. Traditional economic data that are available to all investors are published with lags and suffer from the problem of frequent revisions. Consequently, they often fail to forecast stock returns. For this reason, investors are increasingly interested in seeking alternative data. This paper forecasts stock returns using satellite-based information on shipping containers, which can capture economic activity in real-time. The container coverage area in each port is identified from 83,672 satellite images via the U-Net method and used as a proxy for the number of containers. Forecast combination over univariate predictive regression is used to generate return forecasts. The results indicate that the number of containers in ports can significantly predict stock index returns in 27 out of 33 countries at a daily frequency for the 2019–2021 period. An investor making use of satellite data on marine ports can, on average, receive an annualized return of 16.38%. The predictability can be explained by the predictive relationship between port container numbers and economic activity. In future studies, satellite data can be applied to monitor and forecast other economic indicators.

Abstract Medroxyprogesterone (MPA) has therapeutic effect on endometrial carcinoma (EC), while it could promote the carcinogenesis of breast cancer (BC) by activating receptor activator of NF-kB ligand (RANKL). However, the selective mechanism of MPA in endometrium and breast tissue remains obscure. Multiomics analysis of chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) were performed in cell lines derived from endometrial cancer and mammary tumor to screen the differential co-regulatory factors of progesterone receptor (PR). Dual-luciferase assays and ChIP-PCR assays were used to validate the transcriptional regulation. Co-immunoprecipitation (Co-IP) and immunofluorescence assays were carried out to explore molecular interactions between PR, the cofactor transcriptional repressor GATA binding 1 (TRPS1), and histone deacetylase 2 (HDAC2). Subsequently, human endometrial cancer/breast cancer xenograft models were established to investigate the regulation effect of cofactor TRPS1 in vivo. In the current study, we found that MPA downregulated RANKL expression in a time- and dose-dependent manner in EC, while had the opposite effect on BC. Then PR could recruit cofactor TRPS1 to the promoter of RANKL, leading to histone deacetylation of RANKL to repress its transcription in EC, whereas MPA disassociated the PR/TRPS1/HDAC2 complex to enhance RANKL histone acetylation in BC. Therefore, TRPS1, the coregulator recruited by PR played a critical role in the selective mechanism of progesterone in EC and BC and could become a potential candidate for targeted therapy to improve the anticancer effect of MPA on EC and avoid its carcinogenic effect on BC.

In electrochemically active systems, such as fuel cells, electrolyzers, and batteries, researchers often modify the material chemistry or operating variables at one of the electrodes (e.g., the cathode) to investigate its properties. This approach assumes that changes in measured polarization and cell performance result solely from the modifications made to the selected electrode, while the conditions at the other electrode (e.g., the anode) remain constant. However, the potential interactions between the polarizations of these two electrodes have remained unclear. In our study, we utilize a voltage probe capable of precisely determining electrode polarization. Our findings reveal three key insights: 1. The quantification of electrode polarization becomes feasible through the implementation of a voltage probe. 2. The fuel electrode plays a pivotal role in the performance of state-of-the-art solid oxide cells, with its influence being comparable to that of the oxygen electrode. 3. A reciprocal interaction exists between the two electrodes within a solid oxide cell. Consequently, when there are changes in the chemistry or operational conditions at one electrode, the polarization of the other electrode changes simultaneously.

Abstract Background Benign metastasizing leiomyoma (BML) is a rare disease usually observed in women of reproductive or premenopausal age with a history of uterine myomectomy or hysterectomy. The most common sites of metastases are the pulmonary, and other sites include heart, bones, liver, lymph nodes, bladder, skeletal muscles, and central nervous system. Here, we report a case of a 50 year-old woman with a history of hysterectomy who was initially suspected of uterine sarcoma but was finally confirmed to have BML with lung and lymph node metastases, and discuss the treatment and prognosis of BML. Case presentation A 50 year-old woman with a history of total abdominal hysterectomy presented with mild but persistent abdominal pain for more than 3 months. She was suspected of having uterine sarcoma before surgery and laparoscopic extensive debulking surgery including bilateral oophorectomy, pelvic and para-aortic lymph node dissection to the level of the left renal vein, and transcutaneous dissection of the right inguinal lymph nodes. Pathology confirmed a benign leiomyoma, and the patient was diagnosed with BML. No medication was administered after the surgery, and the follow-up was of no significance. Conclusion Benign metastasizing leiomyoma (BML) is a rare disorder in which histologically benign smooth muscle tumors metastasize to extrauterine sites. Metastases are commonly observed in the lung, liver, lymph nodes, skin, bladder, esophagus, and skeletal muscles. BML is usually misdiagnosed as a malignant tumor before surgery until the pathology confirms its benign nature. However, this treatment remains controversial and undetermined. The prognosis is usually favorable owing to its benign nature.

Abstract Background and Purpose Gut microbes play an important role in the occurrence of lung cancer, immunotherapy, and chemotherapy. In this study, we analyzed the characteristics of gut microbes in patients with lung cancer and investigated the effect of gut microbes on anti‐PD‐1 therapy combined with chemotherapy. Methods Fecal samples from 21 non‐small cell lung cancer (NSCLC) patients and 22 healthy volunteers who were treated in the Fourth Hospital of Hebei Medical University from 2019 to 2021 were collected. DNA was extracted from all samples, and the V3‐V4 region of the bacterial 16S rRNA gene was PCR‐amplified using the Illumina sequencing platform, and R language was used for data analysis. Results There were significant differences in the Beta diversity and metabolic pathways of gut microbes between NSCLC patients and healthy individuals (p

Developing ultrahigh-strength structural materials that are ductile, fracture resistant, and cost effective has been a long-standing desire for scientists and engineers. Surface nano-crystallization technology has recently been developed as one of the most effective methods to optimize surface structure, which can improve local and global mechanical behavior without compromising ductility. This technique involves the use of hundreds of small hard balls vibrated by high-power ultrasound so that they impact onto the surface of a material at high speed, also known as surface mechanical abrasion treatment (SMAT). Despite its success in enhancing the mechanical properties of steels and other structural materials, there is still lack of clear understanding of the relationships between desired surface structures/properties and controlling parameters in such surface treatment processes. Therefore, we calculated residual stress through computational modeling such as finite element analysis (FEA), and simulated the effect of all parameters during processing on residual compressive stress. Different multiple impact models are investigated to develop a more realistic model for the strengthening process.

The drive for sustainable energy solutions has spurred interest in solid oxide fuel cells (SOFCs). This study investigates the impact of sintering temperature on SOFC anode microstructures using advanced 3D focused ion beam–scanning electron microscopy (FIB-SEM). The anode’s ceramic–metal composition significantly influences electrochemical performance, making optimization crucial. Comparing cells sintered at different temperatures reveals that a lower sintering temperature enhances yttria-stabilized zirconia (YSZ) and nickel distribution, volume, and particle size, along with the triple-phase boundary (TPB) interface. Three-dimensional reconstructions illustrate that the cell sintered at a lower temperature exhibits a well-defined pore network, leading to increased TPB density. Hydrogen flow simulations demonstrate comparable permeability for both cells. Electrochemical characterization confirms the superior performance of the cell sintered at the lower temperature, displaying higher power density and lower total cell resistance. This FIB-SEM methodology provides precise insights into the microstructure–performance relationship, eliminating the need for hypothetical structures and enhancing our understanding of SOFC behavior under different fabrication conditions.

Deep learning has emerged as a powerful tool for investigating intricate biological processes in plants by harnessing the potential of large-scale data. Gene regulation is a complex process that transcription factors (TFs), cooperating with their target genes, participate in through various aspects of biological processes. Despite its significance, the study of gene regulation has primarily focused on a limited number of notable instances, leaving numerous aspects and interactions yet to be explored comprehensively. Here, we developed DEGRN (Deep learning on Expression for Gene Regulatory Network), an innovative deep learning model designed to decipher gene interactions by leveraging high-dimensional expression data obtained from bulk RNA-Seq and scRNA-Seq data in the model plant Arabidopsis. DEGRN exhibited a compared level of predictive power when applied to various datasets. Through the utilization of DEGRN, we successfully identified an extensive set of 3,053,363 high-quality interactions, encompassing 1430 TFs and 13,739 non-TF genes. Notably, DEGRN’s predictive capabilities allowed us to uncover novel regulators involved in a range of complex biological processes, including development, metabolism, and stress responses. Using leaf senescence as an example, we revealed a complex network underpinning this process composed of diverse TF families, including bHLH, ERF, and MYB. We also identified a novel TF, named MAF5, whose expression showed a strong linear regression relation during the progression of senescence. The mutant maf5 showed early leaf decay compared to the wild type, indicating a potential role in the regulation of leaf senescence. This hypothesis was further supported by the expression patterns observed across four stages of leaf development, as well as transcriptomics analysis. Overall, the comprehensive coverage provided by DEGRN expands our understanding of gene regulatory networks and paves the way for further investigations into their functional implications.