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Abstract Although Rana chensinensis Ovum (RCO) is enriched with high nutritional value, its quality varies due to the different drying methods used by farmers. This study aims to explore the impact of natural and mechanical drying methods on the nutritional compositions and physicochemical properties of RCO. Five different drying methods were studied, including blast drying (BD), mild breeze light drying (MBLD), natural air drying (NAD), vacuum heat drying (VHD), and vacuum freeze drying (VFD). The quality assessment was based on unsaturated fatty acid (UFA) content, iodine value, estradiol, vitamin E, saponification value, thiobarbituric acid value (TBA), acid value, and antioxidant properties. The results showed that VFD had higher UFA content and lower acid value (139.950 ± 0.397 mg · g−1) and TBA value (0.097 ± 0.003) than others. VFD and NAD had higher iodine values (147.166 ± 1.475 and 146.803 ± 1.209, respectively) than others. There were no significant differences in estradiol, vitamin E, peroxide value and the clearance rates of ABTS+ free radicals and DPPH• free radicals with different drying methods. The findings will provide valuable insights into the industrialization of RCO. Graphical Abstract

Abstract Background This study aimed to evaluate the T2W hypointense ring and T2-FLAIR mismatch signs in gliomas and use these signs to construct prediction models for glioma grading and isocitrate dehydrogenase (IDH) mutation status. Methods Two independent radiologists retrospectively evaluated 207 glioma patients to assess the presence of T2W hypointense ring and T2-FLAIR mismatch signs. The inter-rater reliability was calculated using the Cohen’s kappa statistic. Two logistic regression models were constructed to differentiate glioma grade and predict IDH genotype noninvasively, respectively. Receiver operating characteristic (ROC) analysis was used to evaluate the developed models. Results Of the 207 patients enrolled (119 males and 88 females, mean age 51.6 ± 14.8 years), 45 cases were low-grade gliomas (LGGs), 162 were high-grade gliomas (HGGs), 55 patients had IDH mutations, and 116 were IDH wild-type. The number of T2W hypointense ring signs was higher in HGGs compared to LGGs (p

Abstract Tibetan-speaking patients seeking care in predominantly Mandarin-speaking healthcare settings frequently face communication barriers, leading to potential disparities and difficulties in accessing care. To address this issue, we translated, culturally adapted, and validated the Numerical Pain Rating Scale (NPRS) and the Global Rating of Change (GRoC) into Tibetan (NPRS-Tib and GRoC-Tib), aiming to facilitate cross-linguistic and cross-cultural interactions while examining potential challenges in the adaptation process. Using standard translation-backward translation methods, expert review, pilot testing, and validation through a cross-sectional study with a short-term longitudinal component, we engaged 100 Tibetan patients with musculoskeletal trauma for psychometric validation, including 37 women (aged 22–60 years, mean age 39.1 years). The NPRS-Tib and GRoC-Tib exhibited outstanding psychometric properties, with an Intraclass Correlation Coefficient (ICC) of 0.983 for NPRS-Tib indicating superb test–retest reliability, and expert review confirming good content validity for both instruments. A Spearman's correlation coefficient (Rho) of -0.261 (P = 0.0087) revealed a significant, albeit weak, correlation between changes in NPRS-Tib scores and GRoC-Tib scores. The adaptation process also presented notable challenges, including translation discrepancies from translators' diverse backgrounds and levels of expertise, ambiguity in scale options, and the lack of established tools for criterion validity assessment in Tibetan.

Abstract Asymmetric transformations and synthesis have garnered considerable interest in recent decades due to the extensive need for chiral organic compounds in biomedical, agrochemical, chemical, and food industries. The field of chiral inorganic catalysts, garnering considerable interest for its contributions to asymmetric organic transformations, has witnessed remarkable advancements and emerged as a highly innovative research area. Here, we review the latest developments in this dynamic and emerging field to comprehensively understand the advances in chiral inorganic nanocatalysts and stimulate further progress in asymmetric catalysis.

Abstract Cancer models play critical roles in basic cancer research and precision medicine. However, current in vitro cancer models are limited by their inability to mimic the three-dimensional architecture and heterogeneous tumor microenvironments (TME) of in vivo tumors. Here, we develop an innovative patient-specific lung cancer assembloid (LCA) model by using droplet microfluidic technology based on a microinjection strategy. This method enables precise manipulation of clinical microsamples and rapid generation of LCAs with good intra-batch consistency in size and cell composition by evenly encapsulating patient tumor-derived TME cells and lung cancer organoids inside microgels. LCAs recapitulate the inter- and intratumoral heterogeneity, TME cellular diversity, and genomic and transcriptomic landscape of their parental tumors. LCA model could reconstruct the functional heterogeneity of cancer-associated fibroblasts and reflect the influence of TME on drug responses compared to cancer organoids. Notably, LCAs accurately replicate the clinical outcomes of patients, suggesting the potential of the LCA model to predict personalized treatments. Collectively, our studies provide a valuable method for precisely fabricating cancer assembloids and a promising LCA model for cancer research and personalized medicine.

The grass carp (Ctenopharyngodon idella) holds significant economic value worldwide. However, intensive farming practices often result in lipid metabolic disorder of fish. It is essential to explore the influence of pivotal genes in the process of fat accumulation, particularly from the perspective of fat transport. Fatty acid binding proteins (FABPs) are crucial for selectively binding and transporting free fatty acids (FAs) within cells. Nevertheless, the types of fabp genes in the grass carp genome and their responses to various FAs remain unclear. In the current study, exhaustive bioinformatic analysis identified nine fabp genes in the grass carp genome: fabp1a, fabp1b.1, fabp2, fabp3, fabp6, fabp7a, fabp10a, fabp11a, and fabp11b. Although these genes showed widespread expression across various tissues, each gene displayed distinct preferences for specific primary expression tissues. Notably, fabp1a exhibited prominent expression in muscle, fabp1b.1 in abdominal fat, fabp2 and fabp6 in the intestine, fabp7a in the brain, fabp10a in the hepatopancreas, and fabp11a showed maximal expression in the eye. Findings from primary grass carp hepatocytes revealed that the addition of palmitic acid (PA), high concentrations oleic acid (OA) and docosahexaenoic acid (DHA) (400 µM), significantly increased intracellular lipid accumulation. Intriguingly, the addition of PA resulted in increased expression of fabp2 and fabp11a, while DHA significantly enhanced the expression of fabp7a (P < 0.01). Given that the accumulated FAs are primarily saturated fatty acids, these results suggest that regulating fabps, especially fabp2 and fabp11a, could be a strategy to control fat deposition in grass carp.

SARS-CoV-2 evolves gradually to cause COVID-19 epidemic. One of driving forces of SARS-CoV-2 evolution might be activation of apolipoprotein B mRNA editing catalytic subunit-like protein 3 (APOBEC3) by inflammatory factors. Here, we aimed to elucidate the effect of the APOBEC3-related viral mutations on the infectivity and immune evasion of SARS-CoV-2. The APOBEC3-related C > U mutations ranked as the second most common mutation types in the SARS-CoV-2 genome. mRNA expression of APOBEC3A (A3A), APOBEC3B (A3B), and APOBEC3G (A3G) in peripheral blood cells increased with disease severity. A3B, a critical member of the APOBEC3 family, was significantly upregulated in both severe and moderate COVID-19 patients and positively associated with neutrophil proportion and COVID-19 severity. We identified USP18 protein, a key molecule centralizing the protein-protein interaction network of key APOBEC3 proteins. Furthermore, mRNA expression of USP18 was significantly correlated to ACE2 and TMPRSS2 expression in the tissue of upper airways. Knockdown of USP18 mRNA significantly decreased A3B expression. Ectopic expression of A3B gene increased SARS-CoV-2 infectivity. C > U mutations at S371F, S373L, and S375F significantly conferred with the immune escape of SARS-CoV-2. Thus, APOBEC3, whose expression are upregulated by inflammatory factors, might promote SARS-CoV-2 evolution and spread via upregulating USP18 level and facilitating the immune escape. A3B and USP18 might be therapeutic targets for interfering with SARS-CoV-2 evolution.

The ideal implant surface plays a substantial role in maintaining bone homeostasis by simultaneously promoting osteoblast differentiation and limiting overactive osteoclast activity to a certain extent, which leads to satisfactory dynamic osseointegration. However, the rational search for implant materials with an ideal surface structure is challenging and a hot research topic in the field of tissue engineering. In this study, we constructed titanium dioxide titanium nanotubes (TNTs) by anodic oxidation and found that this structure significantly promoted osteoblast differentiation and inhibited osteoclast formation and function while simultaneously inhibiting the total protein levels of proline-rich tyrosine kinase 2 (PYK2) and focal adhesion kinase (FAK). Knockdown of the PYK2 gene by siRNA significantly suppressed the number and osteoclastic differentiation activity of mouse bone marrow mononuclear cells (BMMs), while overexpression of PYK2 inhibited osteogenesis and increased osteoclastic activity. Surprisingly, we found for the first time that neither knockdown nor overexpression of the FAK gene alone caused changes in osteogenesis or osteoclastic function. More importantly, compared with deletion or overexpression of PYK2/FAK alone, coexpression or cosilencing of the two kinases accelerated the effects of TNTs on osteoclastic and osteogenic differentiation on the surface of cells. Furthermore, in vivo experiments revealed a significant increase in positiveexpression-PYK2 cells on the surface of TNTs, but no significant change in positiveexpression -FAK cells was observed. In summary, PYK2 is a key effector molecule by which osteoblasts sense nanotopological mechanical signals and maintain bone homeostasis around implants. These results provide a referable molecular mechanism for the future development and design of homeostasis-based regulatory implant biomaterials.

As a vital and integral component of transportation infrastructure, pavement has a direct and tangible impact on socio-economic sustainability. In recent years, an influx of groundbreaking and state-of-the-art materials, structures, equipment, and detection technologies related to road engineering have continually and progressively emerged, reshaping the landscape of pavement systems. There is a pressing and growing need for a timely summarization of the current research status and a clear identification of future research directions in these advanced and evolving technologies. Therefore, Journal of Road Engineering has undertaken the significant initiative of introducing a comprehensive review paper with the overarching theme of “advanced road materials, structures, equipment, and detection technologies”. This extensive and insightful review meticulously gathers and synthesizes research findings from 39 distinguished scholars, all of whom are affiliated with 19 renowned universities or research institutions specializing in the diverse and multidimensional field of highway engineering. It covers the current state and anticipates future development directions in the four major and interconnected domains of road engineering: advanced road materials, advanced road structures and performance evaluation, advanced road construction equipment and technology, and advanced road detection and assessment technologies.

This paper conduct an empirical research and investigate the effect of China’s travel purposes on Hungary’s inbound tourism during a period of uncertainty. The study takes into account the influence of the Covid-19 and Ukraine-Russia war on inbound tourism. The short-run monthly sample from January 2018 to July 2022 has been utilzed to capture the uncertain period. A Poisson Regression Model has been applied to calculate the efficacy of China’s travel purposes on Hungary’s inbound tourism. This study finds that China’s leisure and business trips have positive and significant effect on Hungary’s inbound tourism. China’s business trips has a large contribution to Hungary’s inbound tourism than leisure trips. During the uncertain period, the Covid-19 and Ukraine-Russia war had a negative and significant effect on arrivals of tourists to Hungary. Inbound tourism from China to Hungary had contributed positively to the economic performance of Hungary’s tourism sector.

Eco-friendly and efficient strategies for eliminating cadmium (Cd) phytoremediation plant residues are needed. The present study investigated the feasibility of feeding Cd accumulator maize to beef cattle. In total, 20 cattle at 6 months of age were selected and randomly allocated into two groups fed with 85.82% (fresh basis) Cd accumulator maize (CAM) or normal maize (control [Con]) silage diets for 107 d. Feeding CAM did not affect the body weight (P = 0.24), while it decreased feed intake and increased feed efficiency of beef cattle (P

Background: A fractional flow reserve (FFR)-fixed-SYNTAX score could decrease the number of high-risk patients. This study explored the prognostic value of non-invasive quantitative flow ratio (QFR)-fixed-SYNTAX I/II scores in multivessel disease patients. Methods: This was a single-center, small-sample, observational study. Multivessel coronary disease patients were enrolled and finished a 1-year follow-up. SYNTAX scores I/II and functional SYNTAX scores I/II based on QFR (cut-off value of 0.85) were calculated for all patients. The composite occurrence of cardiac deaths, any myocardial infarction, or ischemia-driven revascularization were analyzed using a different score system. Results: A total of 160 patients were stratified into risk groups based on a different scoring system. FSS (functional SYNTAX score) and FSSII (functional SYNTAX score II) reduce the radio of high-risk major adverse cardiovascular events (MACEs), transforming the patients from high-risk to medium- and low-risk. Furthermore, FSSII (hazard ratio (HR): 1.069, 95% CI: 1.025–1.115, p = 0.002) showed a better relationship with MACEs than the other score systems. After recalculating SSII, the survival-free ratio stratified by FSSII decreased from 38.46% to 27.27% in the high-risk group and increased from 84.09% to 86.05% in the low-risk group. Conclusions: FSS or FSSII could decrease the number of high-risk patients compared to SYNTAX score (SS) and FSS. SYNTAX II score (SSII) and FSSII showed a better predictive ability than other scoring systems for under-risk stratification.

Abstract Ionic liquid salts (ILs) are generally recognized as additives in perovskite precursor solutions to enhance the efficiency and stability of solar cells. However, the success of ILs incorporation as additives is highly dependent on the precursor formulation and perovskite crystallization process, posing challenges for industrial‐scale implementation. In this study, a room‐temperature spin‐coated IL, n‐butylamine acetate (BAAc), is identified as an ideal passivation agent for formamidinium lead iodide (FAPbI3) films. Compared with other passivation methods, the room‐temperature BAAc capping layer (BAAc RT) demonstrates more uniform and thorough passivation of surface defects in the FAPbI3 perovskite. Additionally, it provides better energy level alignment for hole extraction. As a result, the champion n–i–p perovskite solar cell with a BAAc capping layer exhibits a power conversion efficiency (PCE) of 24.76%, with an open‐circuit voltage (Voc) of 1.19 V, and a Voc loss of ≈330 mV. The PCE of the perovskite mini‐module with BAAc RT reaches 20.47%, showcasing the effectiveness and viability of this method for manufacturing large‐area perovskite solar cells. Moreover, the BAAc passivation layer also improves the long‐term stability of unencapsulated FAPbI3 perovskite solar cells, enabling a T80 lifetime of 3500 h when stored at 35% relative humidity at room temperature in an air atmosphere.

This study underscores the effectiveness of Qualitative Comparative Analysis (QCA) when compared to conventional regression analysis (CRA) in the investigation of complex human systems. Utilizing historical secondary cross-national data from Lipset & Man (1960) spanning 18 countries, where CRA may be impractical, the research emphasizes the superior performance of QCA, specifically utilizing both crisp set QCA and fuzzy set QCA. The dataset includes variables such as democracy survival and its precursors, such as gross national product per capita, urbanization, literacy rate, and industrial labor force. In contrast to conventional regression results indicating an insignificant relationship between democracy survival and its antecedents, crisp set QCA identifies two distinct combinations of antecedents associated with high levels of democracy survival, albeit with limited solution coverage. Meanwhile, fuzzy set qualitative comparative analysis (fsQCA) reveals five combinations of antecedents linked to robust democracy survival, providing adequate solution coverage and consistency. These findings suggest that fsQCA excels in capturing the intricacies of real-life scenarios in human complex systems, offering more robust empirical solutions compared to crisp set QCA and conventional regression. As a result, researchers may find value in integrating fsQCA into their new projects focused on human complex systems.

Objective: Rece nt studies ha ve revealed that hemoglobin beta (HBB) plays an important role not only in blood disorders but also in malignancies. The aim of this study is to investigate the clinical significance, diagnostic value, and biological function of HBB in lung cancer. Methods: HBB expression was examined in lung cancer tissues and plasma samples using quantitative real-time polymerase chain reaction, and its relationship with clinical pathological characteristics was analyzed. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic value of HBB in lung cancer. The proliferation of A549 and SPCA1 cells was analyzed using a cell counting kit-8 assay and protein expressions were detected by western blot. Results: The expressions of HBB were found to be down-regulated in both lung cancer tissues and plasma samples. Notably, plasma HBB levels were significantly elevated in postoperative samples when compared to their preoperative counterparts. Across 66 cases of lung cancer tissues, a correlation was observed between HBB levels and both gender and tumor, node, metastasis staging. ROC curve analysis further confirmed the high diagnostic potential of HBB expression in lung cancer. Moreover, the combination of HBB and carcinoembryonic antigen (CEA) had greater significance than HBB or CEA alone in the diagnosis of lung cancer. Knocking out or overexpressing HBB could affect lung cancer cell proliferation through the ERK1/2 signaling pathway. Conclusion: HBB can serve as a novel biomarker for the diagnosis and monitoring of lung cancer, regulating cell proliferation via the ERK1/2 pathway and playing a pivotal role in the oncogenesis and progression of the disease.

Older adults with chronic illness, as well as their primary caregivers in multigenerational families, may experience a complex interplay of factors that affect their quality of life (QOL). However, this interplay is not yet well-characterized for Chinese multigenerational families in particular. In this study, we analyzed how family resilience and social support affect the QOL of both older adults and caregivers in multigenerational Chinese families specifically. We enrolled 258 pairs of older adults with chronic illness and their primary caregivers in a multicenter cross-sectional study conducted in southern China in December 2021. Using the Actor-Partner Interdependence Model (APIM), we then examined the correlation between family resilience, social support, and QOL in dyadic analysis and found that QOL, family resilience, and social support for primary caregivers were better than those of older adults with chronic illness (t = 3.66–16.3, p＜0.01). These factors were found to be positively correlated (r = 0.22–0.60, p＜0.05), except for the family resilience of primary caregivers and the QOL of older adults with chronic illness (r = −0.14, p = 0.04). Additionally, actor effect results showed that when a dyadic member has high family resilience and objective social support, they tend to have a better QOL (β = 0.5–1.48, P

Abstract The dimension of the void area in pavement is crucial to its structural safety. However, there is no effective method to measure its geometric parameters. To address this issue, a void size extraction algorithm based on the continuous wavelet transform (CWT) method was proposed using ground-penetrating radar (GPR) signal. Firstly, the finite-difference time-domain (FDTD) method was used to investigate the GPR response of void areas with different shapes, sizes, and depths. Next, the GPR signal was processed using the CWT method, and a 3D image based on the CWT result was used to visualize the void area. Based on the differences between the void and normal pavement in the time and frequency domains, the signal with maximum energy from the CWT time–frequency result was extracted and combined to reconstruct the new B-scan image, where void areas have energy concentration phenomenon. Based on this, width and depth of void detection algorithm was proposed to recognize the void area. Finally, the detection algorithm was verified both in numerical model and physical lab model. The results indicated that the CWT time–frequency energy spectrum can be used to enhance the void feature, and the 3D CWT image can clearly visualize the void area with a highlighted energy area. After fully testing and validating in numerical and lab models, our proposed method achieved high accuracy in void width and depth detection, providing a precise method for estimating void dimension in pavement. This method can guide DOT departments to carry out pre-maintenance, thereby ensuring pavement safety.

Abstract Ruminants play a vital economic role as livestock, providing high-quality protein for humans. At present, 3D-cultured ruminant abomasum and intestinal organoids have been successfully established to study host and pathogen interaction. The rumen is a unique digestive organ of ruminants that occupies 70% of the volume of the digestive tract and its microbiota can decompose lignocellulose to support animal growth. Here we report a method for culturing rumen epithelial organoids. We found that single rumen epithelial cells form self-organized 3D structures representative of typical stratified squamous epithelium, which is similar to rumen epithelium. EGF, Noggin, Wnt3a, IGF-1, and FGF-10 significantly enhanced the seeding efficiency of organoids. Moreover, the inclusion of CHIR-99021, A83-01, SB202190, and Y-27632 is crucial for organoid formation and maintenance. Importantly, we demonstrate that rumen epithelial cells retain their ability to form organoids after passage, cryopreservation, and resuscitation. The rumen epithelial organoids express rumen cell type-specific genes, uptake fatty acids, and generate 2D cultures. In summary, our data demonstrate that it is feasible to establish organoids from single rumen epithelial cells, which is a novel in vitro system that may reduce the use of experimental animals.

Abstract An important pathophysiological process of acute kidney injury (AKI) is mitochondrial fragmentation in renal tubular epithelial cells, which leads to cell death. Pyruvate kinase M2 (PKM2) is an active protein with various biological functions that participates in regulating glycolysis and plays a key role in regulating cell survival. However, the role and mechanism of PKM2 in regulating cell survival during AKI remain unclear. Here, we found that the phosphorylation of PKM2 contributed to the formation of the PKM2 dimer and translocation of PKM2 into the mitochondria after treatment with staurosporine or cisplatin. Mitochondrial PKM2 binds myosin heavy chain 9 (MYH9) to promote dynamin-related protein 1 (DRP1)-mediated mitochondrial fragmentation. Both in vivo and in vitro, PKM2-specific loss or regulation PKM2 activity partially limits mitochondrial fragmentation, alleviating renal tubular injury and cell death, including apoptosis, necroptosis, and ferroptosis. Moreover, staurosporine or cisplatin-induced mitochondrial fragmentation and cell death were reversed in cultured cells by inhibiting MYH9 activity. Taken together, our results indicate that the regulation of PKM2 abundance and activity to inhibit mitochondrial translocation may maintain mitochondrial integrity and provide a new therapeutic strategy for treating AKI.

With the frequency of extreme rainfall increasing, the risk of waterlogging is significantly exacerbated in subway systems. It is imperative to first identify the rainfall threshold for waterlogging risk for subway stations in order to develop effective waterlogging prevention and control plans. This study focuses on Line 11 of the Beijing Subway, using InfoWorks ICM to construct a model of the research area and simulate waterlogging at various subway stations under different rainfall scenarios. The results indicate that there is a risk of waterlogging at Jinanqiao station, Moshikou station, and Beixinan station on Line 11. The accumulated water may enter the subway station through exits A, B, C, and D of Jinanqiao Station. The inlet sequence of Jinanqiao Station always follows A(B), C, and D, and the difference in waterlogging time for each outlet does not exceed 10 min. We derived the rainfall threshold formula for waterlogging risk at Jinanqiao subway station. Among the three influencing factors of topographic features, step height, and drainage capacity of the pipeline network, step height has a significant effect on increasing the rainfall threshold for waterlogging risk. The conclusions obtained can provide reference for the refined management of waterlogging risks in subway stations.

Abstract The inflammatory immune environment surrounding titanium bone implants determines the formation of osseointegration, and nanopatterning on implant surfaces modulates the immune microenvironment in the implant region. Among many related mechanisms, the mechanism by which nanopatterning controls macrophage inflammatory response still needs to be elucidated. In this paper, we found that inhibition of the nuclear envelope protein lamin A/C by titania nanotubes (TNTs) reduced the macrophage inflammatory response. Knockdown of lamin A/C reduced macrophage inflammatory marker expression, while overexpression of lamin A/C significantly elevated inflammatory marker expression. We further found that suppression of lamin A/C by TNTs limited actin polymerization, thereby reducing the nuclear translocation of the actin-dependent transcriptional cofactor MRTF-A, which subsequently reduced the inflammatory response. In addition, emerin, which is a key link between lamin A/C and actin, was delocalized from the nucleus in response to mechanical stimulation by TNTs, resulting in reduced actin organization. Under inflammatory conditions, TNTs exerted favourable osteoimmunomodulatory effects on the osteogenic differentiation of mouse bone marrow-derived stem cells (mBMSCs) in vitro and osseointegration in vivo. This study shows and confirms for the first time that lamin A/C-mediated nuclear mechanotransduction controls macrophage inflammatory response, and this study provides a theoretical basis for the future design of immunomodulatory nanomorphologies on the surface of metallic bone implants.

Abstract Background Esophageal cancer is one of the most common malignant tumors in the world, which is characterized by poor prognosis, aggressiveness, and poor survival. Mucin 13 (MUC13) is a member of the membrane-bound mucin and located on chromosome 3q21.2 and consists of α and β subunits. It has been found that MUC13 is overexpressed in a variety of tumor cells and acts a vital role in the invasiveness and malignant progression of several types of tumors. However, the role and regulatory mechanism of MUC13 in the progression of esophageal cancer remain unclear. Methods The expression level of MUC13 was detected in 15 esophageal cancer tissues and 15 pairs of adjacent nontumor tissues by immunohistochemistry (IHC). In addition, the expression of MUC13 mRNA level in human esophageal cancer cell lines (EC9706 and ECA109 and TE-1) was measured by qRT-PCR. In vitro, after silencing MUC13 with lentiviral interference technology, CCK8 assay, clone formation assay, and flow cytometry were applied to investigate the proliferation activity, clone formation ability and anti-apoptosis ability of EC9706 and ECA109 cells. The tumor xenograft growth assay was used to confirm the influence of MUC13 knockdown on the growth of esophageal tumors in vivo. The qRT-PCR assay and western blot experiments were taken to study the mechanism of MUC13 regulating the proproliferation and antiapoptotic of esophageal cancer. Results The results showed that MUC13 was overexpressed in esophageal cancer tissues and cell lines (EC9706 and ECA109 and TE-1), especially in EC9706 and ECA109 cells, but low expressed in human esophageal epithelial cell line (HEEC). Next, silencing MUC13 inhibits proliferation, blocks cell cycle progression, and promotes cell apoptosis in vitro, and restrains the growth of esophageal cancer tissues in vivo. Finally, MUC13 affects the proproliferation and antiapoptotic by regulating the expression of GLANT14, MUC3A, MUC1, MUC12, and MUC4 that closely related to O-glycan process. Conclusions This study proved that MUC13 is an important molecule that regulates the O-glycan process and then affects the progress of esophageal cancer. MUC13 may be a novel therapeutic target for patients with esophageal cancer.

Background: Despite the widespread adoption of COVID-19 vaccination, a comprehensive understanding of potential vaccine-induced adverse effects, particularly in the context of pregnancy, remains a critical area of investigation. Elevated concerns surround the maternal and neonatal outcomes subsequent to prenatal maternal COVID-19 vaccination. While existing studies have provided insights into the safety profile of COVID-19 mRNA vaccines, the extrapolation of these conclusions to inactivated COVID-19 vaccines poses uncertainties. Notably, limited data are available regarding the maternal and neonatal effects associated with inactivated COVID-19 vaccines.Objective: To evaluate the prenatal maternal inactivated COVID-19 vaccination and the impact on maternal and neonatal outcomes.Methods: This was a retrospective cohort study of women who delivered between January and June 2022 at a single university-affiliated hospital. Those who have completed at least one dose of inactivated vaccine before or during pregnancy were included in “vaccinated group,” and those who were not vaccinated were included in “unvaccinated group,” the maternal, pregnancy and neonatal outcomes were evaluated. Propensity score matching (PSM) was performed to balance the baseline parameters of the two groups.Results: A total of 1926 women were enrolled in this study, 827 (42.94%) women were prenatally vaccinated, and 1099 (57.06%) unvaccinated. The gestational week of delivery were slightly lower in the vaccinated group, 38.61 ± 1.89 weeks in the vaccinated group and 38.93 ± 1.49 weeks in the unvaccinated group. There was a higher rate of overall preterm delivery in the vaccinated group (aOR 1.61, 95% CI 1.07–2.42; p = 0.02), however, the probability of delivery before 34 weeks and before 32 weeks (early preterm delivery) were similar (p > 0.05). A total of 2009 infants were born, 851 in the vaccinated group and 1158 in the unvaccinated group. There were similar neonatal outcomes in the two groups.Conclusion: Although we found a slightly lower gestational week of delivery and a possible increased rate of late preterm birth in the vaccination group, there was no difference in mean neonatal weight, incidence of low birth weight infants and other neonatal adverse complications. Meanwhile, there was no difference in pregnancy and maternal outcomes between the two groups.

In the present study, our aim was to assess the effect of dietary black soldier fly oil (BSFO) with different lipid contents on the growth performance, body composition, lipid metabolism, and related gene expression in juvenile mirror carp (Cyprinus carpio var. specularis). An 8-week feeding trial was conducted using four isonitrogenous diets (32.0% crude protein) containing two lipid levels: 6% (control (CT) group) and 9% (high lipid (HL) group), both using soybean oil as the oil source. The other two diets contained BSFO on the basis of 6% and 9% lipid, referred to as (CT + BSFO) and (HL + BSFO) groups. The results showed that final body weight, weight gain rate, specific growth rate, protein retention ratio, and feed utilization were significantly increased by using higher dietary lipid levels (P

Among the polyphenolic compounds commonly found in green tea, (-)-epigallocatechin-3-gallate (EGCG) is known to have various functions, including the promotion of antioxidant and myofiber growth in mammals. However, the effect of EGCG on common carp (Cyprinus carpio L.) remains poorly understood. To evaluate the role of EGCG on juvenile common carp, 255 fish (initial weight 17.33 ± 0.34 g) were fed with five experimental diets containing 0, 0.05, 0.25, 0.5, and 1 g/kg EGCG. The results showed that diet supplementation with 0.05–0.5 g/kg EGCG supplementation significantly enhanced the specific growth rate (SGR) and reduced the feed conversion ratio (FCR). Weight gain rate (WGR) was significantly enhanced in the 0.25 and 0.5 g/kg EGCG groups. As for antioxidants, 0.25–1 g/kg EGCG significantly reduced protein carbonyl (PC) content and upregulated superoxide dismutase (sod) gene expression in the muscle. As for muscle nutritional composition, 0.05–0.5 g/kg EGCG increased total amino acid (TAA) and flavor amino acid (FAA) contents, likely via the rapamycin (mTOR) signaling pathway. Muscle n-3 polyunsaturated fatty acids (n-3 PUFA) content was increased with 0.5 g/kg EGCG, presumably owing to the upregulation of fatty acyl elongase 5 (elovl5), long-chain fatty acyl-CoA synthetase 6 (acsl6), and peroxisome proliferator-actiated receptor α (pparα). Dietary EGCG (0.05–1 g/kg) significantly increased muscle hardness and chewiness, accompanied by an increase in myofiber density. EGCG supplementation (0.25–1 g/kg) increased the pH value and reduced lactate contents in the muscle. However, muscle crude lipid and hydroxyproline contents significantly decreased with 1 g/kg EGCG. Overall, quadratic regression analysis of WGR, SGR, TAA, and FAA showed that optimal EGCG (0.46–0.52 g/kg) dietary supplementation improved the growth and nutritional composition of juvenile common carp.

Sepsis, a life-threatening condition characterized by organ dysfunction, results from a complex series of pathophysiological mechanisms including immune dysfunction, an uncontrolled inflammatory response, and coagulation abnormalities. It is a major contributor to global mortality and severe disease development. Platelets, abundant in the circulatory system, are sensitive to changes in the body's internal environment and are among the first cells to respond to dysregulated pro-inflammatory and pro-coagulant reactions at the onset of sepsis. In the initial stages of sepsis, the coagulation cascade, inflammatory response, and endothelial tissue damage perpetually trigger platelet activation. These activated platelets then engage in complex inflammatory and immune reactions, potentially leading to organ dysfunction. Therefore, further research is essential to fully understand the role of platelets in sepsis pathology and to develop effective therapeutic strategies targeting the associated pathogenic pathways. This review delves into the involvement of platelets in sepsis and briefly outlines the clinical applications of associated biomarkers.

The multiple global environments have triggered changes in the international environment, leading to a sharp decline of foreign direct investment (FDI) compared to pre-pandemic level. To evaluate the investment risk of FDI and make optimal investment decision becomes the most important issue for investors. This paper focuses on the evaluation of investment risk for FDI. First, an index system for risk evaluation of FDI is constructed. Then, we introduce the probabilistic linguistic entropy and cross entropy measures, based on which, a programming model is developed to identify the objective attribute weights. A composite weight derivation method, which takes both the objective attribute weights and the subjective attribute weights into account, is further introduced. In view of attributes' uncertainty and fuzziness and the conflicting characteristics of some attributes, the VIKOR (the Serbian name: VlseKriterijumska Optimizacija I Kompromisno Resenje, means multi-criteria optimization and compromise solution) method is used to evaluate the risk of FDI under the probabilistic linguistic environment. Furthermore, a case study is presented to illustrate the proposed method. The comparative analysis and some further discussions verify the validity of the proposed method for the FDI risk evaluation.

BackgroundThe impact of decreased bone mineral density (BMD) on traumatic rib fractures remains unknown. We combined computed tomography (CT) and artificial intelligence (AI) to measure BMD and explore its impact on traumatic rib fractures and their patterns.MethodsThe retrospective cohort comprised patients who visited our hospital from 2017–2018; the prospective cohort (control group) was consecutively recruited from the same hospital from February–June 2023. All patients had blunt chest trauma and underwent CT. Volumetric BMD of L1 vertebra was measured by using an AI software. Analyses were done by using BMD categorized as osteoporosis (120 mg/cm3). Pearson’s χ2, Fisher’s exact, or Kruskal–Wallis tests and Bonferroni correction were used for comparisons. Negative binomial, and logistic regression analyses were used to assess the associations and impacts of BMD status. Sensitivity analyses were also performed.FindingsThe retrospective cohort included 2,076 eligible patients, of whom 954 (46%) had normal BMD, 806 (38.8%) had osteopenia, and 316 (15.2%) had osteoporosis. After sex- and age-adjustment, osteoporosis was significantly associated with higher rib fracture rates, and a higher likelihood of fractures in ribs 4–7. Furthermore, both the osteopenia and osteoporosis groups demonstrated a significantly higher number of fractured ribs and fracture sites on ribs, with a higher likelihood of fractures in ribs 1–3, as well as flail chest. The prospective cohort included 205 eligible patients, of whom 92 (44.9%) had normal BMD, 74 (36.1%) had osteopenia, and 39 (19.0%) had osteoporosis. The findings observed within this cohort were in concurrence with those in the retrospective cohort.InterpretationTraumatic rib fractures are associated with decreased BMD. CT-AI can help to identify individuals who have decreased BMD and a greater rib fracture rate, along with their fracture patterns.

Objective This study aimed to analyze the association between sleep quality and cardiovascular disease in patients on maintenance hemodialysis (MHD).Methods A total of 601 patients with MHD in the second affiliated hospital of Nanjing Medical University, were prospectively enrolled in this cohort study from January 2019 to December2019. The global Pittsburgh sleep quality index (PSQI) score > 7 indicates that a person with poor sleep quality. Patients were divided into two groups according to the PSQI score. Follow-up was conducted about 3 years with all-cause death and major adverse cardiovascular events (MACEs) as the endpoint events.Results Of the 601 patients, 595 patients completed the PSQI assessment, with 278 patients having poor sleep quality. Patients in the PSQI > 7 group were older and had a higher proportion of cardiovascular disease or diabetes. Years of education, diastolic blood pressure, and heart rate were lower in the PSQI > 7 group. At a mean follow-up period of 3 years, 116 patients died, 64 patients were lost to follow-up, and 115 patients experienced MACEs. After adjusting for confounding factors such as age, gender, dialysis age, and previous cardiovascular disease, the risk of MACE in patients with poor sleep quality was twice that of patients with good sleep quality (HR = 2.037 (1.339, 3.097), p = 0.001). There was no significant difference in the risk of all-cause death between the two groups.Conclusion The prevalence of poor sleep quality was 46.7% in patients with MHD. Poor sleep quality was an independent risk factor for MACEs in patients with MHD.

ABSTRACT: Stress-induced immunosuppression (SIIS) is one of the common problems in intensive poultry production, which often reduces the prevention and control effects of various vaccines, including infectious bursal disease virus (IBDV) vaccine, and brings enormous economic losses to the poultry industry. However, the molecular mechanisms of SIIS inhibiting immune response to IBDV vaccine remain unclear. In this study, suppressor of cytokine signaling 3 (SOCS3) gene was selected and stress-induced immunosuppressed chickens were simulated using dexamethasone (Dex). Quantitative real-time PCR (qRT-PCR) was conducted to analyze its expression characteristics and game relationships between SOCS3 gene and miR-27b-3p (it could target SOCS3 gene) in the process of SIIS inhibiting immune response to IBDV vaccine in chicken, and the potential application value of circulating miR-27b-3p as a biomarker was also identified. The results showed that SOCS3 gene and miR-27b-3p were significantly differentially expressed in the candidate tissues during SIIS inhibiting the immune response to IBDV (P < 0.05), respectively, which were key factors involved in the process. Moreover, miR-27b-3p and SOCS3 gene showed game regulation relationships in several tissues during the process, so the miR-27b-3p/SOCS3 regulatory network was one of the key mechanisms of SOCS3 gene participating in the process. Circulating miR-27b-3p was differentially expressed in serum at 10 time points (1, 2, 3, 4, 5, 7, 14, 21, 28, and 35 days postimmunization (dpi)) in the process (P < 0.05), showing that circulating miR-27b-3p was a valid candidate target as a molecular marker for detecting SIIS inhibiting the IBDV immune response. This study can provide references for further studying molecular mechanisms of stress affecting immune response.

Abstract Objective To assess the diagnostic efficacy of 18F-FDG PET/MRI for lymph node (LN) metastasis primary staging in patients with colorectal cancer (CRC). Methods This study was conducted and reported in accordance with the PRISMA-DTA statement. Electronic databases (PubMed, Embase, Cochrane Library) were searched for studies on 18F-FDG PET/MRI for diagnosing LN metastasis. The pooled sensitivity (SEN), specificity (SPE), and area under the curve (AUC) were applied to assess the diagnostic performance. Heterogeneity was identified and processed using meta-regression and sensitivity analysis. All data analyses were performed via STATA 15 and Meta-Disc 1.4 software. Results There were finally 7 studies included, involving a total of 184 patients. The Spearman rank correlation coefficient was 0.108 (P = 0.818), with no threshold-effect observed. The pooled SEN was 0.81 (95%CI 0.66–0.90) and the SPE was 0.89 (95% CI 0.73–0.96). In sub-groups, prospective groups demonstrated to have the highest SEN of 0.92 (95%CI 0.79–1.00). The studies conducted by Catalano et al. and Kang et al. were considered to be potential sources of heterogeneity. Conclusion 18F-FDG PET/MRI has shown remarkable diagnostic performance in identification of LN metastases in newly diagnosed CRC patients. It would be of great application value for the primary staging of CRC lymph node metastases.

Abstract Background Cervical cancer is an important public health problem. Conventional colposcopy is inefficient in the diagnosis of cervical lesions and massive biopsies result in trauma. There is an urgent need for a new clinical strategy to triage women with abnormal cervical screening results immediately and effectively. In this study, the high-resolution microendoscopy combined with methylene blue cell staining technology was used to perform real-time in vivo imaging of the cervix for the first time. Methods A total of 41 patients were enrolled in the study. All patients underwent routine colposcopy and cervical biopsy, and high-resolution images of methylene blue-stained cervical lesions were obtained in vivo using microendoscopy. The cell morphological features of benign and neoplastic cervical lesions stained with methylene blue under microendoscopy were analyzed and summarized. The microendoscopy and histopathology findings of the high-grade squamous intraepithelial lesion (HSIL) and more severe lesions were compared. Results The overall consistency of microendoscopy diagnosis with pathological diagnosis was 95.12% (39/41). Diagnostic cell morphological features of cervicitis, low-grade squamous intraepithelial lesion (LSIL), HSIL, adenocarcinoma in situ, and invasive cancer were clearly demonstrated in methylene blue stained microendoscopic images. In HSIL and more severe lesions, microendoscopic methylene blue cell staining technology can show the microscopic diagnostic features consistent with histopathology. Conclusions This study was an initial exercise in the application of the microendoscopy imaging system combined with methylene blue cell staining technology to cervical precancerous lesions and cervical cancer screening. The results provided the basis for a novel clinical strategy for triage of women with abnormal cervical screening results using in vivo non-invasive optical diagnosis technology.

Salt stress poses a serious threat to tomato production. Red to far-red light ratio (R/FR) is actively involved in the regulation of tomato growth and development; however, it is still uncertain whether and how R/FR improves fruit quality under salt stress. Thus, we conducted metabolomic analysis of tomato fruits under four treatments, including R/FR = 7 (CK), R/FR = 0.7 (L), R/FR = 7 and 100 mmol·L−1 NaCl (Na), and R/FR = 0.7 and 100 mmol·L−1 NaCl (Na+L). Metabolomic analysis indicated that both low R/FR and salt stress enhanced organic acids and phenols accumulation; however, additional low R/FR mainly improved carbohydrates, organic acids, phenols and amino acids accumulation in salt-stressed tomato fruit. Physiological studies were consistent with the above results and further revealed that additional low R/FR drastically promoted plant growth, soluble sugar, total phenol and flavonoid contents, improved osmotic pressure balance and antioxidant capacity, and notably relieved the salt stress-induced suppressions. This study proved the importance of applying light quality regulation in salt-resistant tomato production.

Nanoscale agrochemicals have been widely used in sustainable agriculture and may potentially affect the nitrogen fixation process in legume crops. The present study investigated the size-effects of copper oxide nanoparticles (CuO NPs) on nitrogen assimilation in soybean (G. max (L.) Merrill) plants, which were treated with different sizes (20 and 50 nm) of CuO NPs at low use doses (1 and 10 mg/kg) for 21 days under greenhouse conditions. The results showed that 50 nm CuO NPs significantly increased the fresh biomass more than 20 nm CuO NPs achieved at 10 mg/kg. The activities of N assimilation-associated enzymes and the contents of nitrogenous compounds, including nitrates, proteins, and amino acids, in soybean tissues were greatly increased across all the CuO NP treatments. The use doses of two sizes of CuO NPs had no impact on the Cu contents in shoots and roots but indeed increased the Cu contents in soils in a dose-dependent fashion. Overall, our findings demonstrated that both 20 and 50 nm CuO NPs could positively alter soybean growth and boost N assimilation, furthering our understanding that the application of nanoscale micro-nutrient-related agrochemicals at an optimal size and dose will greatly contribute to increasing the yield and quality of crops.

Soybean sprouts constitute a significant segment of the vegetable market due to their nutritional richness, particularly in various flavonoids, which contribute to numerous health benefits. The augmentation of the flavonoid content in soybean sprouts is pivotal for enhancing their economic value. While research has established the potential of blue light in promoting the synthesis of anthocyanins, a subclass of flavonoids known for their health advantages, the precise regulatory mechanisms remain elusive. In this study, we identified a notable upregulation of an R2R3 type MYB transcription factor, GmMYB114, in response to blue light exposure, exhibiting a significant positive correlation with anthocyanin accumulation in soybean sprouts. The functional role of GmMYB114 was validated in soybean hairy roots, wherein its overexpression substantially augmented anthocyanin synthesis. Further investigations employing yeast one-hybrid (Y1H), dual-luciferase reporter (LUC), and GUS assays revealed that GmMYB114 indirectly influences anthocyanin synthesis as it does not directly bind to the promoters of anthocyanin synthesis genes to activate their expression. These findings contribute to elucidating the mechanism underlying blue light-mediated enhancement of anthocyanin synthesis in soybean sprouts, offering valuable insights for harnessing molecular technologies to obtain anthocyanin-enriched soybean sprouts.

Pulse wave velocity (PWV) indicates the degree of vascular stiffness. This study aimed to explore the association between heart rate (HR) and brachial-ankle (ba)-PWV in patients with pacemaker implantation. This retrospective observational study included patients who underwent permanent pacemaker implantation at the Second Hospital of Hebei Medical University between December 2018 and December 2021. All patients were pacemaker-dependent, and the ba-PWV values were collected during HR setted from 60 to 100 bpm. A total of 68 patients (34 males, aged 65.97 ± 9.90 years) were included in this study. There were significant difference of ba-PWV and diastolic blood pressure (DBP) among different HR (both P

Clinical epidemiological studies have confirmed that tobacco smoking disrupts bone homeostasis and is an independent risk factor for the development of osteoporosis. The low viability and inferior osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) are important etiologies of osteoporosis. However, few basic studies have elucidated the specific mechanisms that tobacco toxins devastated BMSCs and consequently induced or exacerbated osteoporosis. Herein, our clinical data showed the bone mineral density (BMD) values of femoral neck in smokers were significantly lower than non-smokers, meanwhile cigarette smoke extract (CSE) exposure led to a significant decrease of BMD in rats and dysfunction of rat BMSCs (rBMSCs). Transcriptomic analysis and phenotype experiments suggested that the ferroptosis pathway was significantly activated in CSE-treated rBMSCs. Accumulated intracellular reactive oxygen species activated AMPK signaling, furtherly promoted NCOA4-mediated ferritin-selective autophagic processes, increased labial iron pool and lipid peroxidation deposition, and ultimately led to ferroptosis in rBMSCs. Importantly, in vivo utilization of ferroptosis and ferritinophagy inhibitors significantly alleviated BMD loss in CSE-exposed rats. Our study innovatively reveals the key mechanism of smoking-related osteoporosis, and provides a possible route targeting on the perspective of BMSC ferroptosis for future prevention and treatment of smoking-related bone homeostasis imbalance.

Abstract Backgrounds Botulinum toxin type A (BoNT/A) is extensively applied in spasticity and dystonia as it cleaves synaptosome-associated protein 25 (SNAP25) in the presynaptic terminals, thereby inhibiting neurotransmission. An increasing number of randomized clinical trials have suggested that glabellar BoNT/A injection improves depressive symptoms in patients with major depressive disorder (MDD). However, the underlying neuronal circuitry of BoNT/A-regulated depression remains largely uncharacterized. Results Here, we modeled MDD using mice subjected to chronic restraint stress (CRS). By pre-injecting BoNT/A into the unilateral whisker intrinsic musculature (WIM), and performing behavioral testing, we showed that pre-injection of BoNT/A attenuated despair- and anhedonia-like phenotypes in CRS mice. By applying immunostaining of BoNT/A-cleaved SNAP25 (cl.SNAP25197), subcellular spatial localization of SNAP25 with markers of cholinergic neurons (ChAT) and post-synaptic membrane (PSD95), and injection of monosynaptic retrograde tracer CTB-488-mixed BoNT/A to label the primary nucleus of the WIM, we demonstrated that BoNT/A axonal retrograde transported to the soma of whisker-innervating facial motoneurons (wFMNs) and subsequent transcytosis to synaptic terminals of second-order neurons induced central effects. Furthermore, using transsynaptic retrograde and monosynaptic antegrade viral neural circuit tracing with c-Fos brain mapping and co-staining of neural markers, we observed that the CRS-induced expression of c-Fos and CaMKII double-positive neurons in the ventrolateral periaqueductal grey (vlPAG), which sent afferents to wFMNs, was down-regulated 3 weeks after BoNT/A facial pre-administration. Strikingly, the repeated and targeted silencing of the wFMNs-projecting CaMKII-positive neurons in vlPAG with a chemogenetic approach via stereotactic injection of recombinant adeno-associated virus into specific brain regions of CRS mice mimicked the antidepressant-like action of BoNT/A pre-treatment. Conversely, repeated chemogenetic activation of this potential subpopulation counteracted the BoNT/A-improved significant antidepressant behavior. Conclusion We reported for the first time that BoNT/A inhibited the wFMNs-projecting vlPAG excitatory neurons through axonal retrograde transport and cell-to-cell transcytosis from the injected location of the WIM to regulate depressive-like phenotypes of CRS mice. For the limited and the reversibility of side effects, BoNT/A has substantial advantages and potential application in MDD.

Abstract Trichoderma reesei (T. reesei) is well-known for its excellent ability to secret a large quantity of cellulase. However, unlike the endogenous proteins, little is known about the molecular mechanisms governing heterologous protein production. Herein, we focused on the integration loci and the secretory pathway, and investigated their combinatorial effects on heterologous gene expression in T. reesei using a glucose oxidase from Aspergillus niger as a model protein. Integration in the cel3c locus was more efficient than the cbh1 locus in expressing the AnGOx by increasing the transcription of AnGOx in the early stage. In addition, we discovered that interruption of the cel3c locus has an additional effect by increasing the expression of the secretory pathway component genes. Accordingly, overexpressing three secretory pathway component genes, that were snc1, sso2, and rho3, increased AnGOx expression in the cbh1 transformant but not in the cel3c transformant.

Abstract Background and purpose Ki-67 labeling index (LI) is an important indicator of tumor cell proliferation in glioma, which can only be obtained by postoperative biopsy at present. This study aimed to explore the correlation between Ki-67 LI and apparent diffusion coefficient (ADC) parameters and to predict the level of Ki-67 LI noninvasively before surgery by multiple MRI characteristics. Methods Preoperative MRI data of 166 patients with pathologically confirmed glioma in our hospital from 2016 to 2020 were retrospectively analyzed. The cut-off point of Ki-67 LI for glioma grading was defined. The differences in MRI characteristics were compared between the low and high Ki-67 LI groups. The receiver operating characteristic (ROC) curve was used to estimate the accuracy of each ADC parameter in predicting the Ki-67 level, and finally a multivariate logistic regression model was constructed based on the results of ROC analysis. Results ADCmin, ADCmean, rADCmin, rADCmean and Ki-67 LI showed a negative correlation (r = − 0.478, r = − 0.369, r = − 0.488, r = − 0.388, all P

Abstract Periodontitis is the most widespread oral disease and is closely related to the oral microbiota. The oral microbiota is adversely affected by some pharmacologic treatments. Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis, causing negative effects on the human body. Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed. In this research, mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss. The results demonstrated, for the first time, that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis. Moreover, the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue. Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier, decreased the pathogenicity of the oral microbiota, reversed the Th17/Treg imbalance in periodontal tissue, and alleviated alveolar bone loss. This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis. A Th17/Treg imbalance might be related to this relationship. Importantly, these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice.

Objective: To improve the prognosis of patients with gastric cancer (GC), more effective therapeutic targets are urgently needed. Increasing evidence indicates that miRNAs are involved in the progression of various tumors, and RAS-associated protein in the brain 31 (RAB31) is upregulated and promotes the progression of multiple malignant tumors. Here, we focused on identifying RAB31-targeted miRNAs and elucidating their potential mechanism in the progression of GC. Methods: RAB31 and miR-378a-3p expression levels were detected in paired fresh GC tissues and GC cell lines. Bioinformatics analysis was used to predict the miRNAs targeting RAB31 and the relationships between RAB31 and other genes. Dual-luciferase reporter assays were applied to verify the targeted interaction relationship. CCK-8, colony formation, flow cytometry, wound healing, and Transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of GC cells. Tumorsphere formation assays were performed to assess the stemness of gastric cancer stem cells. Related proteins were detected by Western blot. Xenograft assays in nude mice were performed to explore the effect of miR-378a-3p in vivo. Results: We report the first evidence that miR-378a-3p is downregulated in GC, whereas its overexpression inhibits proliferation, invasion, and migration as well as promotes apoptosis in GC cells. Mechanistically, miR-378a-3p inhibits the progression of GC by directly targeting RAB31. Restoring RAB31 expression partially offsets the inhibitory effect of miR-378a-3p. Further research revealed that miR-378a-3p inhibits GLI1/2 in the Hedgehog signaling pathway and attenuates the stemness of gastric cancer stem cells. Finally, xenograft assays showed that miR-378a-3p inhibits GC tumorigenesis in vivo. Conclusions: MiR-378a-3p inhibits GC progression by directly targeting RAB31 and inhibiting the Hedgehog signaling pathway proteins GLI1/2.

Abstract Background Gastric neuroendocrine neoplasm (g-NEN) is a rare but heterogeneous neoplasm, with an increasing incidence yearly. Conventional prognostic markers of g-NEN remain limited which could only be detected after surgery. There is an urgent need to explore new prognostic markers for g-NEN patients. This study aimed to investigate the prognostic value of platelet-to-lymphocyte, ratio (PLR) and the association between PLR and body mass index (BMI) in patients with gastric neuroendocrine neoplasms (g-NEN). Methods A retrospective cohort of patients with g-NEN from January 2001 through June 2016 was examined. The prognostic significance of PLR was determined by multiple regression analysis in different models. Stratified analysis was performed to examine the prognostic value of PLR at different BMI levels. Results In total, 238 patients were enrolled. Those with higher PLRs tended to undergo open surgery, had larger tumor sizes, were diagnosed more frequently with neuroendocrine carcinoma, and had higher tumor grades. PLR was significantly associated with the survival of patients with g-NEN. With PLR increased per standard deviation, the all-cause mortality risk of patients with g-NEN increased by 67%, 63%, and 54% in the crude (HR = 1.67, 95% CI 1.32–2.12, P < 0.001), minimally adjusted (HR = 1.63, 95% CI 1.28–2.08, P < 0.001), and fully adjusted (HR = 1.54, 95% CI 1.202–1.98, P = 0.001) models, respectively. Patients with higher PLR (quartile 4, ≥ 187) had a 1.8-fold increase in all-cause mortality risk compared with those with lower PLR (quartile 1–3, < 187). Furthermore, there was a significant interaction effect between BMI subgroups and PLR in predicting the survival of patients with g-NEN (PLR regarded as a continuous variable: all P for interaction < 0.05 in the crude, minimally adjusted, and fully adjusted models; PLR regarded as a categorical variable: P for interaction < 0.05 in the fully adjusted model). Patients with g-NEN with the characteristics of higher PLR (quartile 4, ≥ 187) and non-obesity (BMI < 25 kg/m2) had worse survival than others (P < 0.05). Conclusion The inflammation marker PLR has an independent prognostic value for patients with g-NENs, and high PLR combined with non-obesity increases the mortality risk of these patients.

To study the effect of drilling rig working parameters and rock type on the temperature of the polycrystalline diamond composite (PDC) bit, an analytical temperature calculation model was established, and the correctness of the analytical model was verified by numerical simulation analysis. Combined with an infrared thermal imager, the temperature of PDC cutting teeth under different parameter combinations was qualitatively analyzed, and the sensitivity of cutting teeth temperature to different parameters was discussed through an orthogonal test. The research results show that increasing the rotational speed and rate of penetration (ROP) value causes more severe shearing and friction of the bit, thereby increasing the temperature of the cutting teeth. The experimental results are consistent with the simulation results. Under the same working parameters, the maximum temperature of the bit when drilling granite is about 1.5 times that of curbs and 2 times that of artificial rocks. Finally, the orthogonal test analysis found that the cutting teeth temperature has a high sensitivity to rock type and ROP value, with a weight of 48% and 32.9%, respectively; also, the index has a general sensitivity to the rotation speed, with a weight of 19.1%. The research results provide a certain reference value for the reasonable selection of the working parameters of the drilling rig.

Abstract Background Accurate tumor staging is the cornerstone of tumor treatment. Current tumor staging system for gastric cancer (GC) is based on regional positive lymph nodes while ignoring the total number of examined lymph nodes. We aim to assess the prognostic value of lymph node density (LND), the ratio of positive nodes to the total number examined nodes, in GC without distal metastasis. Methods Clinical information of patients with histologically confirmed GC and without distal metastasis was identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The X-Tile software was used to identify the ideal prognosis-related cutoff point for LND. The prognostic value of LND on cancer-specific survival (CSS) and overall survival (OS) was assessed in Cox regression models. Subgroup analysis stratified by LND was performed on current lymph node staging system to further explore the interaction between LND and current lymph node staging system. Results A total of 4281 participants were identified from the SEER database for the final analysis. The optimal prognosis-related cutoff values of LND were calculated as 0.1 and 0.4, and LND was divided into three levels: LND1 (< 0.1), LND2 (> = 0.1, < 0.4), and LND3 (> = 0.4). LND3 was associated with worse CSS and OS in GC patients. Compared to patients with LND1, those with LND2 and LND3 had 2.43 (HR = 2.43, 95% CI 2.09–2.84, P < 0.001) and 4.69 (HR = 4.69, 95% CI 4.02–5.48, P < 0.001) folds increase in mortality in CSS, respectively. Similar results were found in the evaluation of OS in GC patients. Subgroup analysis stratified by LND also found that patients in the same current lymph node stage still had different prognosis due to the different LND levels after adjustment for other prognosis-related covariates (all P values < 0.001). Conclusion LND is an independent prognostic factor for GC without distal metastasis. In the current lymph node staging system, LND has potential value in further accurately classifying GC patients without distal metastasis.

This work is the first attempt to reveal the chemical compositions, as well as the relationships between the chemical compositions and anti-fatigue effect of Oviductus Ranae (OR) and Rana chensinensis ovum (RCO). In this work, an integrated strategy was applied containing comprehensive chemical profiling analysis, extraction methods, in vivo study, multivariate statistics, and network pharmacology. Here, 138 compounds were identified or briefly characterized using UPLC-Q/TOF-MS. About 24 and 35 variables were considered to be discriminating compounds from petroleum ether and ethanol extracts of OR and RCO, respectively. In addition, 41 identified compounds in OR and RCO were significantly correlated with anti-fatigue parameters. Finally, 22 candidate markers in OR and RCO were screened. Network pharmacology analysis was employed to verify those markers and screen the potential targets for anti-fatigue effect. Screened targets were further validated using RT-PCR. In muscle tissues, AKT mRNA, PI3K mRNA, and mTOR mRNA were upregulated following OR and RCO administration. This work not only paved the way for further study of OR and RCO in anti-fatigue function, but also provided essential information for their products quality control.

Abstract Gastric cancer (GC) is one of the most commonly diagnosed malignancies worldwide. Compelling evidence indicates that circular RNA (circRNA) played critical roles in multiple cancers. However, the role and mechanisms of circRNAs in GC remains unclear. Here we first identified a notably overexpressed circular RNA hsa_circ_0025506 in GC by human circRNA microarray, designated as circGPRC5A(e2). Next, we found circGPRC5A(e2) was overexpressed in GC cell lines and clinical samples as well. Then, we confirmed that circGPRC5A(e2) was primarily located in the cytoplasm of GC cells and colocation phenomenon was observed with miR‐665 via fluorescence in situ hybridization. Functionally, Cell Counting Kit‐8, 5‐Ethynyl‐2′‐deoxyuridine, clone formation assay, Transwell invasion assay, wound‐healing assay, and animal experiments showed that circGPRC5A(e2) promoted GC proliferation, migration, and invasion in vitro, and tumorigenesis and metastasis in vivo. Mechanistically, we showed that circGPRC5A(e2) could serve as miR‐665 sponges and facilitate GC growth and metastasis via modulating miR‐665/LIM and SH3 protein 1 (LASP1) axis and activating phosphatidylinositol 3‐kinase/AKT pathway. Taken together, this study revealed that circGPRC5A(e2) functioned as an oncogene in GC. The circGPRC5A(e2)/miR‐665/LASP1 axis revealed by current research might provide novel biomarkers and promising therapeutic targets for GC.

Matrix stiffness plays an important role in determining cell differentiation. The expression of cell differentiation-associated genes can be regulated by chromatin remodeling-mediated DNA accessibility. However, the effect of matrix stiffness on DNA accessibility and its significance for cell differentiation have not been investigated. In this study, gelatin methacryloyl (GelMA) hydrogels with different degrees of substitution were used to simulate soft, medium, and stiff matrices, and it was found that a stiff matrix promoted osteogenic differentiation of MC3T3-E1 cells by activating the Wnt pathway. In the soft matrix, the acetylation level of histones in cells was decreased, and chromatin condensed into a closed conformation, affecting the activation of β-catenin target genes (Axin2, c-Myc). Histone deacetylase inhibitor (TSA) was used to decondense chromatin. However, there was no significant increase in the expression of β-catenin target genes and the osteogenic protein Runx2. Further studies revealed that β-catenin was restricted to the cytoplasm due to the downregulation of lamin A/C in the soft matrix. Overexpression of lamin A/C and concomitant treatment of cells with TSA successfully activated β-catenin/Wnt signaling in cells in the soft matrix. The results of this innovative study revealed that matrix stiffness regulates cell osteogenic differentiation through multiple pathways, which involve complex interactions between transcription factors, epigenetic modifications of histones, and the nucleoskeleton. This trio is critical for the future design of bionic extracellular matrix biomaterials.

ABSTRACT: Adipose tissue (AT) is considered as a regional immune organ and plays an important role in the anti-infection immune response. However, the function and mechanism of chicken AT in response to secondary immune response remain poorly understood. Here, we used mRNA and microRNA (miRNA) sequencing technology to survey the transcriptomic landscape of chicken abdominal adipose tissue (AAT) during the first and second immunization with Newcastle disease virus (NDV) vaccine, and carried out bioinformatics analysis, such as Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis, protein–protein interaction (PPI) analysis, and miRNA–mRNA integrated analysis. The results indicated that chicken AAT actively responded to the secondary immune response. DNA replication and cytoskeleton regulation as the regulatory functions of immune activation changed significantly, and weakened lipid metabolism was an effective strategy for the secondary immunity. Mechanically, the regulatory network between the differentially expressed miRNAs (DEMs) and their targeted differentially expressed genes (DEGs), such as miR-206/miR-499-5p-nuclear receptor subfamily 4 group A member 3 (NR4A3)/methylsterol monooxygenase 1 (MSMO1) pathway, was one of the potential key mechanisms by which AAT responded to the secondary immune response. In conclusion, regional immunity of chicken AT responds to secondary immunity by promoting immune activation and weakening lipid metabolism, and this study can instruct future research on antiviral strategy.

Lipid metabolism plays an important role in maintaining lipid homeostasis and regulating immune functions. However, the regulations and mechanisms of lipid metabolism on the regional immune function of avian adipose tissue (AT) have not been reported. In this study, qRT-PCR was used to investigate the changes and relationships of different lipid metabolism pathways in chicken AT during stress-induced immunosuppression (SIIS) inhibiting immune response to Newcastle disease virus vaccine, then the miRNA regulation patterns of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) gene and its potential applications were further identified. The results showed that AT actively responded to SIIS, and ATGL, CPT1A and HMGCR were all the key genes involved in the processes of SIIS inhibiting the immune responses. SIIS significantly inhibited the natural and specific immune phases of the primary immune response and the initiation phase of the secondary immune response in AT by suppressing T cells by up-regulating steroid anabolism. Moreover, steroid metabolism could play dual roles in regulating the regional immune functions of AT. The miR-29a/c-3p-HMGCR network was a potential regulation mechanism of steroid metabolism in AT, and serum circulating miR-29a/c-3p had the potential as molecular markers. The study can provide valuable references for an in-depth investigation of the regional immune functions regulated by lipid metabolism in AT.