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Abstract This study aimed to investigate the characteristics and prognosis of distant metastasis (DM) after primary treatment for early‐stage extranodal nasal‐type natural killer (NK)/T‐cell lymphoma (ENKTCL). A total of 1619 patients from the China Lymphoma Collaborative Group database were retrospectively reviewed. The cumulative incidence of DM was assessed using Fine and Gray's competing risk analysis. The correlation between DM sites was evaluated using phi coefficients, while DM sites were classified using hierarchical clustering. Regression analysis was used to assess the linear correlation between DM‐free survival (DMFS) and overall survival (OS). The 5‐year cumulative DM rate was 26.2%, with the highest annual hazard rate being in the first year (14.9%). The most frequent DM sites were the skin and soft tissues (SSTs, 32.4%) and distant lymph nodes (LNs, 31.3%). DM sites were categorized into four subgroups of distinct prognosis — distant LN, SST, extracutaneous site, and lymphoma‐associated hemophagocytic lymphohistiocytosis. SST or distant LN, solitary metastasis, and late‐onset DM demonstrated a relatively favorable prognosis. Contemporary chemotherapy significantly decreased DM rates and improved DMFS. Decreased DM rates were further associated with increased OS probabilities. Our findings improve the understanding of the variable clinical behaviors of early‐stage ENKTCL based on four distinct DM sites and thus provide guidance for future therapeutic decisions, metastatic surveillance, and translational trial design.

Abstract Let ( M , g ) $(M,g)$ be an n-dimensional complete Riemannian manifold with nonnegative Ricci curvature. In this paper, we consider an overdetermined problem of the biharmonic operator on a bounded smooth domain Ω in M. We deduce that the overdetermined problem has a solution only if Ω is isometric to a ball in R n $\mathbb{R}^{n}$ . Our method is based on using a P-function and the maximum principle argument. This result is a generalization of the overdetermined problem for the biharmonic equation in Euclidean space.

Dietary compounds are crucial in maintaining human physiological functions and preventing diseases, but they can give full play to their functional activities only after being effectively absorbed and utilized by the human body. In vitro intestinal cell models have become an effective means to study the absorption and utilization mechanism of dietary compounds. Selecting the appropriate intestinal cell model and improving the existing intestinal cell models are of great significance to effectively simulate the absorption and utilization of dietary compounds in human body. In this paper, the structure and function of human intestinal epithelial cells are introduced, and recent progress in research on in vitro intestinal cell models is systematically reviewed. The intestinal absorption and transport mechanism of carotenoids is expounded, and the focus of this review is on the application of the Caco-2 single cell model and the Caco-2/HT29-MTX co-culture cell model in research on the absorption and utilization of carotenoids, so as to provide a reference for better simulation of absorption and utilization of dietary compounds in human body by using the in vitro intestinal cell absorption models.

Abstract Background Magnetic resonance imaging (MRI) performs well in the locoregional assessment of extranodal nasal-type NK/T-cell lymphoma (ENKTCL). It’s important to assess the value of multi-modal MRI-based radiomics for estimating overall survival (OS) in patients with ENKTCL. Methods Patients with ENKTCL in a prospectively cohort were systemically reviewed and all the pretreatment MRI were acquisitioned. An unsupervised spectral clustering method was used to identify risk groups of patients and radiomic features. A nomogram-revised risk index (NRI) plus MRI radiomics signature (NRI-M) was developed, and compared with the NRI. Results The 2 distinct type I and II groups of the MRI radiomics signatures were identified. The 5-year OS rates between the type I and type II groups were 87.2% versus 67.3% (P = 0.002) in all patients, and 88.8% versus 69.2% (P = 0.003) in early-stage patients. The discrimination and calibration of the NRI-M for OS prediction demonstrated a better performance than that of either MRI radiomics or NRI, with a mean area under curve (AUC) of 0.748 and 0.717 for predicting the 5-year OS in all-stages and early-stage patients. Conclusions The NRI-M model has good performance for predicting the prognosis of ENKTCL and may help design clinical trials and improve clinical decision making.

Delineating the specific role of Polycomb Repressive Complex 2 (PRC2) in various cancer systems is desirable as inhibitors for EZH2 inhibitors are approved for some cancers. Here the authors show haplo- and full-insufficiency of EZH2 drive divergent phenotypes in lung cancer. 3D tumoroids recapitulate transcriptional profiles, including FOXP2 derepression, and drug responses of in vivo tumors.

Abstract Background Diarrheal irritable bowel syndrome (IBS-D) is a common chronic functional gastrointestinal disorder, and the underlying pathogenic mechanism is still unclear. Animal models that mimic the pathological state of IBS-D patients were constructed to provide a reference for later drug research and model development. Methods The IBS-D model was induced using restraint stress and chemical stimulation (rhubarb), and rats were divided into normal control group (NC), chemically stimulated group (CS), and restraint stress group (RS). Visceral motility responses to Colorectal Balloon Dilation (CRD) were measured by Abdominal Withdrawal Reflex (AWR); evaluation of faecal properties and water content; determination of colonic tissue tight junction (TJ) mRNA expression by RT-PCR; measurement of inflammatory cytokines by ELISA; and intestinal flora and short chain fatty acids. Results Compared to NC group, CS and RS group rats showed increased intestinal sensitivity and Bristol stool score, significant diarrheal symptoms and weight loss. Mucin 2, ZO-1, OCLN, CLDN4 mRNA expression was reduced and the intestinal mucosal barrier function was diminished. In addition, the levels of inflammatory factors IL-1β, IL-6, IL-8, IL-10 and TNF-α increased, the abundance and diversity of intestinal flora decreased, the content of beneficial bacteria such as Bifidobacteria decreased, and SCFAs such as acetic acid, propionic acid and butyric acid decreased to different degrees. Although, no significant difference was observed for any molecular and inflammatory marker, but compared to CS group, RS group had less water in the stool, higher visceral sensitivity, and higher relative abundance of beneficial intestinal bacteria such as Actinobacteria. Conclusion In conclusion, restraint stress combined with chemical stimulation can mimic the pathological state of diarrhoea symptoms, visceral hypersensitivity, reduced intestinal mucosal barrier permeability, immune regulatory dysfunction and dysbiosis in IBS-D patients. However, herbs with antibacterial effects such as rhubarb and senna, for example, are not suitable as the first choice for chemical stimulation, as they may lead to a decrease in harmful bacteria and an increase in beneficial bacteria in the intestinal fraction and do not perfectly mimic the imbalanced state of intestinal flora in IBS-D patients, while restraint stress may be a key factor in modelling.

Summary: Aberrant lung cell differentiation is a hallmark of many lung diseases including chronic obstructive pulmonary disease (COPD). The EZH2-containing Polycomb Repressive Complex 2 (PRC2) regulates embryonic lung stem cell fate, but its role in adult lung is obscure. Histological analysis of patient tissues revealed that loss of PRC2 activity was correlated with aberrant bronchiolar cell differentiation in COPD lung. Histological and single-cell RNA-sequencing analyses showed that loss of EZH2 in mouse lung organoids led to lowered self-renewal capability, increased squamous morphological development, and marked shifts in progenitor cell populations. Evaluation of in vivo models revealed that heterozygosity of Ezh2 in mice with ovalbumin-induced lung inflammation led to epithelial cell differentiation patterns similar to those in COPD lung. We also identified cystathionine-β-synthase as a possible upstream factor for PRC2 destabilization. Our findings suggest that PRC2 is integral to facilitating proper lung stem cell differentiation in humans and mice.

[Introduction] Under the "carbon peak and neutrality" goal, China's hydrogen energy has great potential. Based on the status quo of China's hydrogen energy industry development, this paper studies the paths and policies for the high-quality development of hydrogen energy in China around the existing problems. [Method] Relevant policies, literature, and cases at home and abroad were sorted out, analyzed, and summarized from the two perspectives of path and policy. [Result] In terms of paths, using hydrogen energy to promote the decarbonization of the energy system in transportation and industry, integrating hydrogen energy with the existing oil and gas energy storage and transportation pipeline system, using hydrogen energy to standardize renewable energy, developing hydrogen production by electrolysis (photovoltaic, wind and other renewable energy power generation), increasing the commercial promotion of hydrogen fuel cells, etc., are effective paths for the high-quality development of hydrogen energy in China. In terms of policy, improving the top-level policy design of national hydrogen energy, refining the policies support for special research on hydrogen energy "production, storage, transportation and utilization," accelerating the formulation of hydrogen energy-related standards and norms, strengthening the construction of strategic alliances of the hydrogen energy industry and improving the coordination of supply and demand in the hydrogen energy market, etc., are essential guarantees [Conclusion] The relevant path suggestions and policy discussions mentioned in the research can provide a reference for relevant departments and industry personnel.

To address the issues of excessive heat loss from the roofs of multi-span greenhouses and high energy consumption for heating during winter production, we propose an approach for the external insulation of the roof of multi-span glass greenhouses and have developed an external insulation system (EIS) to practice this approach. The system achieved full coverage of the greenhouse roof through mechanized unfurling and furling of external thermal blankets, thereby achieving energy-saving insulation. This paper describes the overall design and working method of the EIS, providing detailed design and structural parameters for critical components such as the traction rope transmission mechanism and the rail-type sealing structure. Through a system verification experiment, the specifications of the traction rope were determined and the rationality of the EIS’s thermal blanket unfurling and furling time was confirmed. An insulation performance experiment indicated that the average heat flux of the greenhouse roof covered with the external thermal blanket over 14 continuous nights was 54.2 W/m2, compared with 198.6 W/m2 for a single-layer glass roof. Covering the roof with the external thermal blanket reduced heat loss from the glass roof by 72.7%. The average heat flux of the roof of the Venlo-type multi-span greenhouse with double-layer internal insulation was 99.9 W/m2 during the same period, indicating that the heat loss from the roof using external insulation was only 50.3%. This study provides a novel thermal insulation approach and an energy-saving system for multi-span greenhouses.

Spinetoram is an important semi-synthetic insecticide extensively applied in agriculture. It is neurotoxic to insects, primarily by acting on acetylcholine receptors (nAChRs). However, few studies have examined the neurotoxicity of spinetoram in human beings. In this study, various concentrations (5, 10, 15, and 20 μM) of spinetoram were employed to expose SH-SY5Y cells in order to study the neurotoxic effects of spinetoram. The results showed that spinetoram exposure markedly inhibited cell viability and induced oxidative stress. It also induced mitochondrial membrane potential collapse (ΔΨm), and then caused a massive opening of the mitochondrial permeability transition pore (mPTP), a decrease in ATP synthesis, and Ca2+ overloading. Furthermore, spinetoram exposure induced cellular autophagy, as evidenced by the formation of autophagosomes, the conversion of LC3-I into LC3-II, down-regulation of p62, and up-regulation of beclin-1. In addition, we observed that p-mTOR expression decreased, while p-AMPK expression increased when exposed to spinetoram, indicating spinetoram triggered AMPK/mTOR-mediated autophagy. Complementarily, the effect of spinetoram on neurobehavior was studied using the zebrafish model. After being exposed to different concentrations (5, 10, and 20 μg/mL) of spinetoram, zebrafish showed neurobehavioral irregularities, such as reduced frequency of tail swings and spontaneous movements. Similarly, autophagy was also observed in zebrafish. In conclusion, spinetoram exposure produced potential neurotoxicity through autophagy mediated by mitochondrial damage. The experimental data and results of the neurotoxicity study of spinetoram provided above are intended to serve as reference for its safety assessment.

In the published publication [...]

Millions of craniofacial surgeries are performed annually worldwide, and materials for craniofacial bone repair are widely needed. However, traditionally applied materials, such as titanium and polymethylmethacrylate, have some shortcomings (limited malleability, material-based toxicity, non-biodegradability, lack of bioactivity, etc.). Zinc based biodegradable metals possess superior mechanical properties, biodegradability, and bioactivity, which make them promising candidate materials. Here, we successfully fabricated Zn-0.6Cu thin sheets (thickness ≤0.5 mm, suitable for craniofacial surgery) through combined extrusion and rolling. The in vitro and in vivo performances were generally evaluated and compared to those of a commercially applied pure titanium mesh. The mechanical properties of Zn-0.6Cu sheets were superior to those of clinically used polymethyl methacrylate. They were easy to shape and would not fracture during deformation. The Zn-0.6Cu sheet exhibited a gentle degradation mode, and proper implant-derived Zn improved osteogenic differentiation of rat bone marrow mesenchymal stem cells by up-regulating expression of osteogenesis related genes (alkaline phosphatase, bone morphogenetic protein-2). Thus, it further promoted extracellular matrix mineralization by improving calcium deposition for bone formation. It also improved the expression of angiogenesis-related genes (vascular endothelial growth factor, hypoxia-inducible factor alpha). The Zn-0.6Cu sheet exhibited high osteogenic activity in a cranial defect animal model compared to a non-biodegradable pure titanium mesh. Significant surface degradation occurred after two months in vivo, and degradation products were compatible with surrounding tissues. In general, the Zn-0.6Cu thin sheet seems to be a bioactive material selection for craniofacial bone repair, which might possibly accelerate defect repair and prevent adverse complications.

AimsTo explore the clinical characteristics of patients with symptomatic duodenal diverticula and to generalize how to make appropriate treatment choices for this group of patients.Materials and methodsFrom January 2010 to September 2020, a total of 647 patients with duodenal diverticula (DD) were included in this study. 345 of them with relevant symptoms were divided into the symptomatic group and the other 302 patients were in the asymptomatic group.ResultsAmong all patients, most DD were located in the periampullary area,

The Coronavirus Disease 2019 (COVID-19) pandemic continues to infect people worldwide. While the vaccinated population has been increasing, the rising breakthrough infection persists in the vaccinated population. For living with the virus, the dietary guidelines to prevent virus infection are worthy of and timely to develop further. Tannic acid has been demonstrated to be an effective inhibitor of coronavirus and is under clinical trial. Here we found that two other members of the tannins family, oligomeric proanthocyanidins (OPCs) and punicalagin, are also potent inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with different mechanisms. OPCs and punicalagin showed inhibitory activity against omicron variants of SARS-CoV-2 infection. The water extractant of the grape seed was rich in OPCs and also exhibited the strongest inhibitory activities for viral entry of wild-type and other variants in vitro. Moreover, we evaluated the inhibitory activity of grape seed extractants (GSE) supplementation against SARS-CoV-2 viral entry in vivo and observed that serum samples from the healthy human subjects had suppressive activity against different variants of SARS-CoV-2 Vpp infection after taking GSE capsules. Our results suggest that natural tannins acted as potent inhibitors against SARS-CoV-2 infection, and GSE supplementation could serve as healthy food for infection prevention.

ABSTRACT: Oxidative stress can trigger follicular atresia, and decrease follicles quantity in each development stage, thereby alleviating reproductive activity. The induction of oxidative stress in chickens through intraperitoneal injection of dexamethasone is a reliable and stable method. Melatonin has been shown to mitigate oxidative stress in this model, but the underlying mechanism remains unclear. Therefore, this study aimed to investigate whether melatonin can recover aberrant antioxidant status induced by dexamethasone and the specific mechanism behind melatonin-dependent protection. A total of 150 healthy 40-wk-old Dawu Jinfeng laying hens with similar body weights and laying rates were randomly divided into three groups, with five replicates per group and 10 hens per replicate. The hens in the control group (NS) received intraperitoneal injections of normal saline for 30 d, the dexamethasone group (Dex+NS) received 20 mg/kg dose of dexamethasone for the first 15 d, followed by the 15 d of normal saline treatment. While in the melatonin group (Dex+Mel), dexamethasone (20 mg/kg dose) was injected intraperitoneally in the first 15 d, and melatonin (20 mg/kg/d) was injected in the last 15 d. The results showed that dexamethasone treatment significantly enhanced oxidative stress (P < 0.05), while melatonin not only inhibited the oxidative stress but also notably enhanced the antioxidant enzymes superoxide dismutase (SOD), catalase activity (CAT), glutathione peroxidase (GSH-Px), and antioxidant genes CAT, superoxide dismutase 1 (SOD1), glutathione peroxidase 3 (GPX3), and recombinant peroxiredoxin 3 (PRDX3) expression (P < 0.05). Melatonin treatment also markedly reduced 8-hydroxy deoxyguanosine (8-OHdG), malondialdehyde (MDA), and reactive oxygen species (ROS) levels (P < 0.05) and apoptotic genes Caspase-3, Bim, and Bax in the follicle. In the Dex+Mel group, the Bcl-2 and SOD1 protein levels were also increased (P < 0.05). Melatonin inhibited the forkhead Box Protein O1 (FOXO1) gene and its protein expression (P < 0.05). In general, this investigation revealed that melatonin might decrease oxidative stress and ROS by enhancing antioxidant enzymes and genes, activating the antiapoptotic genes, and inhibiting the FOXO1 pathway in laying hens.

Abstract Mode interactions have recently become the focus of intense research in micro/nanoelectromechanical systems (M/NEMS) due to their ability to improve device performance and explore the frontiers of fundamental physics. Understanding and controlling coupling between vibrational modes are critical for the development of advanced M/NEMS devices. This review summarizes the recent advances in studies of coupling between multiple modes in M/NEMS resonators, focusing especially on experimental developments and practical applications. First, depending on spatial distribution of interacting modes, this review divides the coupled mechanism in three types: intermode, near‐neighbor, and long‐range coupling. Then, several fundamental physics approaches based on mechanical‐mode coupling, including linear and nonlinear coupling, modal localization, synchronization, and phonon manipulation are reviewed. This review also introduces sensing applications by using coupled mechanical modes. Finally, the state‐of‐the‐art open questions and challenges are reviewed.

The retrotransposon known as long interspersed nuclear element-1 (LINE-1), which is currently the sole autonomously mobile transposon in the human genome, can result in insertional mutations, chromosomal rearrangements, and genomic instability. In recent years, numerous studies have shown that LINE-1 is involved in the development of various diseases and also plays an important role in the immune regulation of the organism. The expression of LINE-1 in gynecologic tumors suggests that it is expected to be an independent indicator for early diagnosis and prognosis, and also, as a therapeutic target, LINE-1 is closely associated with gynecologic tumor prognosis. This article discusses the function of LINE-1 in the diagnosis, treatment, and prognosis of ovarian, cervical, and endometrial malignancies, as well as other gynecologic malignancies. It offers fresh perspectives on the early detection of tumors and the creation of novel anti-tumor medications.

Background Systemic Immune-inflammation Index (SII) and body composition parameters are easily assessed, and can predict overall survival (OS) in various cancers, allowing early intervention. This study aimed to assess the correlation between CT-derived body composition parameters and SII and OS in patients with advanced gastric cancer receiving dual programmed death-1 (PD-1) and human epidermal growth factor receptor 2 (HER2) blockade.Materials and methods This retrospective study enrolled patients with advanced gastric cancer treated with dual PD-1 and HER2 blockade from March 2019 to June 2022. We developed a deep learning model based on nnU-Net to automatically segment skeletal muscle, subcutaneous fat and visceral fat at the third lumbar level, and calculated the corresponding Skeletal Muscle Index, skeletal muscle density, subcutaneous fat area (SFA) and visceral fat area. SII was computed using the formula that total peripheral platelet count×neutrophil/lymphocyte ratio. Univariate and multivariate Cox regression analysis were used to determine the associations between SII, body composition parameters and OS.Results The automatic segmentation deep learning model was developed to efficiently segment body composition in 158 patients (0.23 s/image). Multivariate Cox analysis revealed that high SII (HR=2.49 (95% CI 1.54 to 4.01), p