Search

Abstract Background Horsfieldia hainanensis Merr., an indicator species of China’s humid tropical rainforests, is endangered due to difficulties with population regeneration. In this study, the biological characteristics and germination adaptability of the seeds were studied for the first time, in order to provide a basis for analyzing the causes of endangerment and strategies for the artificial cultivation of H. hainanensis. The effects of biological characteristics (population, arils, seed coat, seed weight, seed moisture content) and environmental factors (temperature, light, drought, substrate, burial depth) on seed germination and seedling growth of H. hainanensis were studied. Results and discussion The fruits were found to be capsules containing seeds wrapped in a pericarp and fleshy aril, which provide protection and assist in seed dispersal, but also pose risks to the seeds, as the peel and fleshy aril can become moldy under high temperature and humidity conditions. There were significant differences in fruit morphology and germination characteristics among different populations, and the seed quality of populations in Niandian village, Daxin County, Chongzuo City, Guangxi Zhuang Autonomous Region was better. The arils significantly inhibited seed germination, the germination of large seeds was better, and seedling growth from medium seeds was superior. H. hainanensis seeds were sensitive to dehydration, and intolerant to drought and low temperature, which is typical of recalcitrant seeds. The seeds are suitable for germination on a moist substrate surface with good water retention and breathability at 30–35℃.

An unprecedented electrochemical oxidative trifunctionalization of olefins with diaryl disulfides/aryl thiols and N-chlorosuccinimide in an aqueous system is developed. Two C–Cl bonds, one C–S bond, and one SO bond are produced simultaneously in one step from simple and commercially available starting materials with clean energy. This tandem methodology features as mild reaction conditions, transition metal and additional oxidant free, broad substrate scope, good functional group compatibility, and gram scale preparation.

Decisions regarding adjuvant therapy in patients with stage II colon cancer remains controversial and challenging. We aimed to determine novel biomarkers that help to predict relapse free survival (RFS) and identify a subset of patients with stage II colon cancer who could gain survival benefits from adjuvant chemotherapy. Public microarray datasets of stage II colon cancer samples were extracted from Gene Expression Omnibus database. Global gene expression changes were then analyzed between the paired early relapse and long-term survival group to identify the differentially expressed mRNAs and lncRNAs. Based on Lasso Cox regression modeling analysis, a total of 30 mRNAs and 2 lncRNAs were finally identified. With specific formula, stage II patients in training and validation sets were divided into low and risk groups with significantly different RFS. PAX8-AS1 is the novel lncRNA which showed the highest upregulation in early relapse group. Patients with high PAX8-AS1 expression level showed notably poorer RFS in both meta GEO cohort (P = 0.04, Figure 4B) and FUSCC cohort (P < 0.001, Figure 4C). Among the stage II patients with high PAX8-AS1 level, administration of fluorouracil-based adjuvant chemotherapy provided a substantial improvement in RFS (P = 0.002, Figure 3C). Further mechanistic study unveiled that PAX8-AS1 increases the response of CRC cells to chemotherapy in vitro and in vivo by maintaining the mRNA stability of PAX8. In conclusion, PAX8-AS1 as a novel and reliable biomarker for predicting prognosis and identification of patients with stage II disease who could gain survival benefit from fluorouracil-based adjuvant chemotherapy.

Abstract As one of the most prevalent digestive system tumours, colorectal cancer (CRC) poses a significant threat to global human health. With the emergence of immunotherapy and target therapy, the prognosis for the majority of CRC patients has notably improved. However, the subset of patients with BRAF exon 15 p.V600E mutation (BRAFV600E) has not experienced remarkable benefits from these therapeutic advancements. Hence, researchers have undertaken foundational investigations into the molecular pathology of this specific subtype and clinical effectiveness of diverse therapeutic drug combinations. This review comprehensively summarised the distinctive molecular features and recent clinical research advancements in BRAF‐mutant CRC. To explore potential therapeutic targets, this article conducted a systematic review of ongoing clinical trials involving patients with BRAFV600E‐mutant CRC.

Syringin, a phenylpropanoid glycoside, is widely distributed in various plants, such as Acanthopanax senticosus (Rupr. et Maxim.) Harms, Syringa reticulata (BL) Hara var. mandshurica (Maxim.) Hara, and Ilex rotunda Thumb. It serves as the main ingredient in numerous listed medicines, health products, and foods with immunomodulatory, anti-tumor, antihyperglycemic, and antihyperlipidemic effects. This review aims to systematically summarize syringin, including its physicochemical properties, plant sources, extraction and separation methods, total synthesis approaches, pharmacological activities, drug safety profiles, and preparations and applications. It will also cover the pharmacokinetics of syringin, followed by suggestions for future application prospects. The information on syringin was obtained from internationally recognized scientific databases through the Internet (PubMed, CNKI, Google Scholar, Baidu Scholar, Web of Science, Medline Plus, ACS Elsevier, and Flora of China) and libraries. Syringin, extraction and separation, pharmacological activities, preparations and applications, and pharmacokinetics were chosen as the keywords. According to statistics, syringin can be found in 23 families more than 60 genera, and over 100 species of plants. As a key component in many Chinese herbal medicines, syringin holds significant research value due to its unique sinapyl alcohol structure. Its diverse pharmacological effects include immunomodulatory activity, tumor suppression, hypoglycemic action, and hypolipidemic effects. Additionally, it has been shown to provide neuroprotection, liver protection, radiation protection, cardioprotection, and bone protection. Related preparations such as Aidi injection, compound cantharidin capsule, and Tanreqing injection have been widely used in clinical settings. Other studies on syringin such as extraction and isolation, total synthesis, safety profile assessment, and pharmacokinetics have also made progress. It is crucial for medical research to deeply explore its mechanism of action, especially regarding immunity and tumor therapy. Meanwhile, more robust support is needed to improve the utilization of plant resources and to develop extraction means adapted to the needs of industrial biochemistry to further promote economic development while protecting people’s health.

The objective of this study was to investigate the function of the aquaporin 4 gene (LvAQP4), which had previously been characterized in Pacific white shrimp, Litopenaeus vannamei. To achieve this, double-stranded RNA (dsRNA) targeting LvAQP4 was synthesized and injected into shrimp, resulting in a significant reduction in the expression of LvAQP4. Subsequent to the evaluation of the impact of LvAQP4 transcriptional silencing on shrimp under salinity challenges, we observed that the downregulation of LvAQP4 expression in the gills resulted in the downregulation of aquaglyceroporin (LvAQP3) and unorthodox aquaporin (LvAQP11) genes, as well as ion transporter genes, such as LvNKAα, LvNKAβ, LvCAc, and LvVHA-a. Notably, the inhibition of LvAQP4 had a significant impact on the expression patterns of these osmoregulatory genes, particularly during periods of high salinity stress. Furthermore, there was a notable increase in the mortality rate of shrimp under high-salinity stress. Moreover, the suppression of LvAQP4 through RNA interference led to a significant delay in the molting rate of shrimp. Furthermore, it resulted in an increase in the expression of LvMIH and a significant reduction in key genes involved in the ecdysone signaling pathway, including LvEcR, LvRXR, and LvE75. These findings suggest that LvAQP4 may play a regulatory role in the molting process of shrimp by modulating MIH and the ecdysone signaling pathway. Moreover, this study lays the groundwork for future investigations into the functions of aquaporins in shrimp osmoregulation and growth, contributing to an enhanced understanding of these essential regulatory mechanisms.

Objective:This experiment aimed to obtain the relatively rare cis-crocetin isomer from natural plants, which predominantly exist in the more stable all-trans configuration. This was achieved through iodine-induced isomerization, followed by purification and structural identification. The study also aimed to compare the pharmacokinetic differences between cis- and trans-crocetin in vivo.Methods:Trans-crocetin of high purity was extracted by hydrolysis from gardenia yellow pigment. Cis-crocetin was then synthesized through an optimized electrophilic addition reaction induced by elemental iodine, and subsequently separated and purified via silica gel column chromatography. Structural identification of cis-crocetin was determined using IR, UV, and NMR techniques. In vivo pharmacokinetic studies were conducted for both cis- and trans-crocetin. In addition to this, we have conducted a comparative study on the in vivo anti-hypoxic activity of trans- and cis-crocetin.Results:Under the selected reaction conditions using DMF as the solvent, with a concentration of 2.5 mg/mL for both trans-crocetin and the iodine solution, and adjusting the illumination time according to the amount of trans-crocetin, the rate of iodine-induced isomerization was the fastest. Cis-crocetin was successfully obtained and, after purification, its structure was identified and found to be consistent with reported data. Cis-crocetin exhibited a faster absorption rate and higher bioavailability, and despite its shorter half-life, it could partially convert to trans-crocetin in the body, thereby extending the duration of the drug’s action within the body to some extent.Conclusion:This study accomplished the successful preparation and structural identification of cis-crocetin. Additionally, through pharmacokinetic studies, it uncovered notable variations in bioavailability between cis- and trans-crocetin. These findings serve as a solid scientific foundation for future functional research and practical applications in this field.

Abstract The lack of human‐derived in vitro models that recapitulate cervical pre‐cancerous lesions has been the bottleneck in researching human papillomavirus (HPV) infection‐associated pre‐cancerous lesions and cancers for a long time. Here, a long‐term 3D organoid culture protocol for high‐grade squamous intraepithelial lesions and cervical squamous cell carcinoma that stably recapitulates the two tissues of origin is described. Originating from human‐derived samples, a small biobank of cervical pre‐tumoroids and tumoroids that faithfully retains genomic and transcriptomic characteristics as well as the causative HPV genome is established. Cervical pre‐tumoroids and tumoroids show differential responses to common chemotherapeutic agents and grow differently as xenografts in mice. By coculture organoid models with peripheral blood immune cells (PBMCs) stimulated by HPV antigenic peptides, it is illustrated that both organoid models respond differently to immunized PBMCs, supporting organoids as reliable and powerful tools for studying virus‐specific T‐cell responses and screening therapeutic HPV vaccines. In this study, a model of cervical pre‐cancerous lesions containing HPV is established for the first time, overcoming the bottleneck of the current model of human cervical pre‐cancerous lesions. This study establishes an experimental platform and biobanks for in vitro mechanistic research, therapeutic vaccine screening, and personalized treatment for HPV‐related cervical diseases.

Background Restrictive cardiomyopathy (RCM) is characterized by impaired diastolic function with preserved ventricular contraction. Several pathogenic variants in sarcomere genes, including TNNI3, are reported to cause Ca2+ hypersensitivity in cardiomyocytes in overexpression models; however, the pathophysiology of induced pluripotent stem cell (iPSC)‐derived cardiomyocytes specific to a patient with RCM remains unknown. Methods and Results We established an iPSC line from a pediatric patient with RCM and a heterozygous TNNI3 missense variant, c.508C>T (p.Arg170Trp; R170W). We conducted genome editing via CRISPR/Cas9 technology to establish an isogenic correction line harboring wild type TNNI3 as well as a homozygous TNNI3‐R170W. iPSCs were then differentiated to cardiomyocytes to compare their cellular physiological, structural, and transcriptomic features. Cardiomyocytes differentiated from heterozygous and homozygous TNNI3‐R170W iPSC lines demonstrated impaired diastolic function in cell motion analyses as compared with that in cardiomyocytes derived from isogenic‐corrected iPSCs and 3 independent healthy iPSC lines. The intracellular Ca2+ oscillation and immunocytochemistry of troponin I were not significantly affected in RCM‐cardiomyocytes with either heterozygous or homozygous TNNI3‐R170W. Electron microscopy showed that the myofibril and mitochondrial structures appeared to be unaffected. RNA sequencing revealed that pathways associated with cardiac muscle development and contraction, extracellular matrix‐receptor interaction, and transforming growth factor‐β were altered in RCM‐iPSC‐derived cardiomyocytes. Conclusions Patient‐specific iPSC‐derived cardiomyocytes could effectively represent the diastolic dysfunction of RCM. Myofibril structures including troponin I remained unaffected in the monolayer culture system, although gene expression profiles associated with cardiac muscle functions were altered.

Liquidambar formosana is an excellent landscape ecological tree species because its beautiful tree shape and red or orange leaves in autumn. In order to understand the genetic basis of discoloration and secondary metabolism of L. formosana leaves, the mixed samples of L. formosana leaves in five leaf discoloration stages were used for full-length transcriptome sequencing using single-molecule real-time sequencing technology (PacBio platform). The results were as follows: (1) High-quality 41.04 Gb data were obtained by full-length transcriptome sequencing, from which 563 180 full-length non-chimeric sequences were identified, and 27 269 high-quality full-length transcripts were obtained by clustering and de-redundancy. In 27 269 full-length transcripts, 2 035 long-chain non-coding RNA (lncRNA) were predicted, and 14 892 simple sequence repeat (SSR) sites and 1 856 transcription factors were detected. (2) The results of gene annotation showed that a total of 24 857 transcripts were annotated in eight databases such as NR, GO, COG and KEGG, etc., 124 metabolic pathways were obtained in KEGG database, including ribosome, carbon metabolism, amino acid biosynthesis and so on, and 49 and 71 transcripts were involved in flavonoid and chlorophyll metabolism respectively. The above results preliminarily reveal the transcriptome information and functional characteristics of L. formosana leaves during the leaf discoloration stage, and provide basic data for the follow-up study of the molecular mechanism of leaf discoloration, the pathway and regulation of pigment metabolism and synthesis, the cloning of related functional genes and the improvement of leaf color.

Polycyclic aromatic hydrocarbons (PAHs) are persistent environmental pollutants commonly found in water and sediments, posing significant health risks due to their toxicity, carcinogenicity, and mutagenicity. The stable and sustainable degradation of PAHs has garnered significant attention from researchers. Biological electrochemical systems (BESs) offer a promising approach with advantages in energy efficiency, safety, environmental protection, and long-term operation. This review examines the degradation performance and microbial community dynamics of BESs in the treatment of PAH-contaminated water and sediments. Additionally, the metabolites formed during the degradation process were also summarized. This review summarizes the degradation characteristics of PAH-contaminated water and sediments and aims to guide future research and optimize BESs for effective remediation of PAHs in various environmental settings.

Crocetin is an aglycone of crocin naturally occurring in saffron and has been proved to have antioxidant, anti-inflammatory, and antibacterial activities. In this experiment, the protective effect of crocetin on vital organs in high-altitude hypoxia rats was studied. Crocetin was prepared from gardenia by the alkaline hydrolysis method, and its reducing ability and free radical scavenging ability were tested. The in vitro anti-hypoxia vitality was studied on PC12 cells. The anti-hypoxic survival time of mice was determined in several models. The acute hypoxic injury rat model was established by simulating the hypoxic environment of 8000 m-high altitude for 24 h, and the anti-hypoxia effect of crocetin was evaluated by intraperitoneal injection with the doses of 10, 20, and 40 mg/kg. The water contents of the brain and lung were determined, and the pathological sections in the brain, lung, heart, liver, and kidney were observed by HE staining. The levels of oxidative stress (SOD, CAT, H2O2, GSH, GSH-Px, MDA) and inflammatory factors (IL-1β, IL-6, TNF-α, VEGF) in rat brain, lung, heart, liver, and kidney tissues were detected by ELISA. The results indicated that crocetin exhibited strong reducing ability and free radical scavenging ability and could improve the activity of PC12 cells under hypoxia. After intraperitoneal injection with crocetin, the survival time of mice was prolonged, and the pathological damage, oxidative stress, and inflammation in rats’ tissue were ameliorated. The protective activity of crocetin on vital organs in high-altitude hypoxia rats may be related to reducing oxidative stress and inhibiting inflammatory response.

Abstract Introduction Colon cancer remains one of the most prevalent cancers worldwide. Unfortunately, there are no recognized and effective therapeutic strategies to prevent tumor recurrence after radical resection and chemotherapy, and the disease-free survival (DFS) in patients with stage IIIB or IIIC disease remains unsatisfactory. Xian-Lian-Jie-Du optimization decoction (XLJDOD) is a Chinese herbal medicine (CHM) empirical prescription, which has been validated experimentally and clinically that could inhibit the progression of colorectal cancer and ameliorate the symptoms. The purpose of this study is to evaluate the efficacy and safety of XLJDOD in prevention of recurrence of colon cancer. Methods This study is a multi-center, double-blind, randomized, placebo-controlled trial conducted at 13 hospitals of China. Following the completion of surgery and adjuvant 5- fluorouracil-based chemotherapy, a total of 730 subjects with stage IIIB or IIIC colon cancer will be randomized in a 1:1 ratio to an intervention group (n = 365; XLJDOD compound granule) and a control group (n = 365; Placebo). Patients will receive 6-month treatments and be followed up with 3 monthly assessments for 2 years. The primary outcome is 2-year DFS rate and the secondary outcomes are 1, 2-year relapse rate (RR), overall survival (OS) and quality of life (QoL). Safety outcomes such as adverse events will be also assessed. A small number of subgroup analysis will be carried out to explore the heterogeneity of effects of XLJDOD. Discussion The outcomes from this randomized controlled trial will provide objective evidences to evaluate XLJDOD’s role as an adjuvant treatment in colon cancer. Trial registration www.ClinicalTrials.gov , identifier: NCT05709249. Registered on 31 Jan 2023.

Esophageal cancer is a major global health challenge with a poor prognosis. Recent studies underscore the extracellular matrix (ECM) role in cancer progression, but the full impact of ECM-related genes on patient outcomes remains unclear. Our study utilized next-generation sequencing and clinical data from esophageal cancer patients provided by The Cancer Genome Atlas, employing the R package in RStudio for computational analysis. This analysis identified significant associations between patient survival and various ECM-related genes, including IBSP, LINGO4, COL26A1, MMP12, KLK4, RTBDN, TENM1, GDF15, and RUNX1. Consequently, we developed a prognostic model to predict patient outcomes, which demonstrated clear survival differences between high-risk and low-risk patient groups. Our comprehensive review encompassed clinical correlations, biological pathways, and variations in immune response among these risk categories. We also constructed a nomogram integrating clinical information with risk assessment. Focusing on the TENM1 gene, we found it significantly impacts immune response, showing a positive correlation with T helper cells, NK cells, and CD8+ T cells, but a negative correlation with neutrophils and Th17 cells. Gene Set Enrichment Analysis revealed enhanced pathways related to pancreatic beta cells, spermatogenesis, apical junctions, and muscle formation in patients with high TENM1 expression. This research provides new insights into the role of ECM genes in esophageal cancer and informs future research directions.

Severe endometrial injury caused by invasive uterine operation and/or endometritis often results in intrauterine adhesions (IUAs), which are named Asherman’s syndrome (AS), further leading to menstrual disorders, infertility and severe complications during pregnancy and delivery. IUAs or AS has been a challenging medical problem. Stem cells are a promising therapeutic modality for endometrial regeneration in patients with refractory AS. Here, we developed a new system of adipose‐derived mesenchymal stem cells (ADMSCs) implantation on silk fibroin/polycaprolactone (SF/PCL) electrospun nanofibers (ADMSCs-SF/PCL) and used it in the damaged endometrium of a rat model. After SF/PCL enhanced the proliferation of transplanted ADMSCs, the results showed that the ADMSCs-SF/PCL system could recover morphology, promote regeneration of the glands and angiogenesis by increasing CD31 expression, and reverse endometrial fibrosis by decreasing TGF-β/Smad expression. In addition, the ADMSCs-SF/PCL system also increased the expression of differentiation and decidualization markers, including HOXA11, HAND2 and FOXO1. Most importantly, the ADMSCs-SF/PCL system could remodel the special immune microenvironment, resulting in dominant NK infiltration and a normal Th1/Th2 bias in the endometrium. Moreover, this treatment had a lower but more persistent effect than estrogen. Thus, the ADMSCs-SF/PCL system enhanced endometrial restoration, suggesting a promising strategy for damaged endometrial regeneration and immune microenvironment remodeling.

Abstract Ubiquitin-specific proteases (USPs) are closely related to protein fate and cellular processes through various molecular signalling pathways, including DNA damage repair, p53, and transforming growth factor-β (TGF-β) pathways. In recent years, increasing evidence has revealed the pivotal role of ubiquitination in tumorigenesis of KIRC. However, USPs' molecular mechanism and clinical relevance in kidney cancer still need further exploration. Our study first determined prognosis-related ubiquitin-specific proteases (PRUSPs) in KIRC. We found these genes co-expressed with each other and might regulate different substrates. Based on the USPs' expression, the PRUSPs risk signature was constructed to predict the survival probability of KIRC patients. The patients in high-PRUSPs-risk group showed a low survival rate. ROC and calibration curve indicated a discriminate capacity of the signature, and uni-/multi-variate Cox regression analysis revealed that the PRUSPs score is an independent prognostic factor. In different KIRC clinical subgroups and external validation cohorts (including E-MTAB-1980 and TCGA-KIRP cohorts), the PRUSPs risk signature showed strong robustness and practicability. Further analysis found that high-risk group showed activation of immune-related pathways and high PD-1/CTLA4 expression, revealing that high-risk patients might be sensitive to immunotherapy. In summary, we constructed the USPs risk signature to predict kidney cancer prognosis, which provided the theoretical foundation for further clinical or pre-clinical experiments.

The numerical solutions of stress and strain components on the critical plane of tungsten carbide coating were solved based on the critical plane method in three-dimensional coordinate system, and accordingly three strain energy density parameters (Smith-Watson-Topper, Nita-Ogatta-Kuwabara and Chen parameters) were determined to reveal the fretting fatigue characteristics of tungsten carbide coating. In order to predict the fretting fatigue life based on the strain energy density criterion, the expressions between the strain energy density parameter and the fretting fatigue life was obtained experimentally. After the comparison of the three strain energy parameters, it was found that all three parameters could accurately predict the crack initiation position, but only the Smith-Watson-Topper parameters could accurately predict the crack initiation angle. The effects of cyclic load, normal load and friction coefficient on fretting fatigue damage behaviors were discussed by using the Smith-Watson-Topper criterion. The results show that the fretting fatigue life decreases with the increase of cyclic load; an increase in the normal contact load will cause the Smith-Watson-Topper damage parameters more concentrated at the outer edge of the bridge foot; a decrease in the friction coefficient will increase the Smith-Watson-Topper damage parameters in the middle of the contact surface.

Glioma is the most common malignant intracranial tumor, accounting for 80 % of all malignant brain tumors. Growing evidence suggests that lncRNAs are involved in the growth, angiogenesis, metastasis, and therapeutic resistance in a variety of tumors, including glioma. In this study, lncBIRC3-OT (NONHSAT159592.1), which is highly expressed in glioma, was screened by RNA-seq method and verified by quantitative reverse transcription polymerase chain reaction. Subsequently, we knocked down the endogenous expression of lncBIRC3-OT in U87 and U251 cells and found that down-regulated lncBIRC3-OT inhibited cell proliferation, colony formation, migration, and invasion. Mechanically, lncBIRC3-OT could guide RELA protein to the stanniocalcin-1 (STC1) promoter, initiate STC1 transcription, and ultimately promote the progression of glioma. Together, these findings suggest that lncBIRC3-OT is an important regulator promoting glioma progression, and may be a promising therapeutic target for glioma.

Lithium-ion batteries have become the best choice for battery energy storage systems and electric vehicles due to their excellent electrical performances and important contributions to achieving the carbon-neutral goal. With the large-scale application, safety accidents are increasingly caused by lithium-ion batteries. As the core component for battery energy storage systems and electric vehicles, lithium-ion batteries account for about 60% of vehicular failures and have the characteristics of the rapid spread of failure, short escape time, and easy initiation of fires, so the safety improvement of lithium-ion batteries is urgent. This study analyses the causes and mechanisms of lithium-ion batteries failures from design, production, and application, investigates its failure features and warning algorithms for thermal runaway, and the concept of long-medium-short graded warning is proposed based on the battery failure mechanism and its evolution to provide a basis for failure warning. As lithium-ion batteries fires are difficult to completely avoid, the characteristics of lithium-ion batteries fires are explored to improve battery structure and develop fire extinguishing agents and methods for fire prevention and suppression. Improving the safety of batteries is a systematic project, and at a time when there has been no breakthrough in the chemical system, improvements, such as build a practical graded warning system, are needed in all aspects of design, production, use and disposal to improve battery safety and minimize the risk of failure.

High-resolution networks have demonstrated significant advantages in multi-scale feature extraction for human pose estimation task. However, this often leads to the problems of large network parameter quantity and high computational complexity. On the other hand, some existing lightweight high-resolution networks have lower model parameter quantity and computational complexity, but they lack accuracy in handling keypoint position information. To address these issues, this study proposes a lightweight High-resolution network called DB-HRNet (Dual Branch High-Resolution Network) for human pose estimation. Specifically. based on HRNet, a more efficient network framework is designed as the backbone framework of DB-HRNet. Additionally, we propose a position-sensitive basic module called DBBlock (Dual Branch Block) to enhance the model’s ability to capture positional information accurately, as the basic block of DB-HRNet. Finally, we propose a Pose Refine Module to establish the connections between keypoints and make the final adjustments to the model’s output. To validate the effectiveness of DB-HRNet, we conduct experimental studies on the COCO2017 and MPII human pose estimation datasets, comparing DB-HRNet with several advanced existing lightweight human pose estimation models. The results demonstrate that the proposed network model achieves a 1.8 points improvement in detection accuracy on the COCO2017 dataset compared to the advanced lightweight high-resolution network Dite-HRNet, while also achieving a 38% increase in model inference speed.

Micro-expressions are brief, involuntary facial movements that reveal genuine emotions. However, extracting and learning features from micro-expressions poses challenges due to their short duration and low intensity. To address this problem, we propose the ADMME (Action Decouple Multi-tasking for Micro-Expression Recognition) method. In our model, we adopt a pseudo-siamese network architecture and leverage contrastive learning to obtain a better representation of micro-expression motion features. During model training, we utilize focal loss to handle the class imbalance issue in micro-expression datasets. Additionally, we introduce an AU (Action Unit) detection task, which provides a new inductive bias for micro-expression detection, enhancing the model’s generalization and robustness. Through five-class classification experiments conducted on the CASMEII and SAMM datasets, we achieve accuracy rates of 86.34% and 81.28%, with F1 scores of 0.8635 and 0.8168, respectively. These results validate the effectiveness of our method in micro-expression recognition tasks. Furthermore, we validate the effectiveness of each component of our approach through a series of ablation experiments.

Central macrosegregation and coarse microstructure are the main defects in ingot castings of high alloy steels. Rapid cooling associated with continuous casting could be beneficial in improving the internal quality of ingot castings. This work evaluated the effects of superheat and cooling intensity on the solidification structure and macrosegregation in 6Cr13Mo stainless steel billet. Numerical modeling was performed to determine the cooling conditions of a continuous casting billet. The simulated cooling conditions were used to solidify 6Cr13Mo steel samples in a thermal simulator. Experimental results suggest that low superheat of the melt combined with an increased cooling intensity reduce central segregation and form refine microstructure. Relationships between the macrosegregation index, (Km_i), of solute elements in the final solidification zone and secondary dendritic arm spacing (λ2), which inversely proportional to cooling rates, conform to simple monotonic equations. Such monotonic relationships indicate that increasing cooling rates is an effective way of reducing central macrosegregation and refining microstructure of 6Cr13Mo steel billet.

Abstract Background Abnormal expression of protein tyrosine phosphatases (PTPs) has been reported to be a crucial cause of cancer. As a member of PTPs, protein tyrosine phosphatase receptor type O (PTPRO) has been revealed to play tumor suppressive roles in several cancers, while its roles in colorectal cancer (CRC) remains to be elucidated. Hence, we aimed to explore the roles and mechanisms of PTPRO in CRC initiation and progression. Methods The influences of PTPRO on the growth and liver metastasis of CRC cells and the expression patterns of different lipid metabolism enzymes were evaluated in vitro and in vivo. Molecular and biological experiments were conducted to uncover the underpinning mechanisms of dysregulated de novo lipogenesis and fatty acid β‐oxidation. Results PTPRO expression was notably downregulated in CRC liver metastasis compared to the primary cancer, and such a downregulation was associated with poor prognosis of patients with CRC. PTPRO silencing significantly promoted cell growth and liver metastasis. Compared with PTPRO wild‐type mice, PTPRO‐knockout mice developed more tumors and harbored larger tumor loads under treatment with azoxymethane and dextran sulfate sodium. Gene set enrichment analysis revealed that PTPRO downregulation was significantly associated with the fatty acid metabolism pathways. Blockage of fatty acid synthesis abrogated the effects of PTPRO silencing on cell growth and liver metastasis. Further experiments indicated that PTPRO silencing induced the activation of the AKT serine/threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling axis, thus promoting de novo lipogenesis by enhancing the expression of sterol regulatory element‐binding protein 1 (SREBP1) and its target lipogenic enzyme acetyl‐CoA carboxylase alpha (ACC1) by activating the AKT/mTOR signaling pathway. Furthermore, PTPRO attenuation decreased the fatty acid oxidation rate by repressing the expression of peroxisome proliferator‐activated receptor alpha (PPARα) and its downstream enzyme peroxisomal acyl‐coenzyme A oxidase 1 (ACOX1) via activating the p38/extracellular signal‐regulated kinase (ERK) mitogen‐activated protein kinase (MAPK) signaling pathway. Conclusions PTPRO could suppress CRC development and metastasis via modulating the AKT/mTOR/SREBP1/ACC1 and MAPK/PPARα/ACOX1 pathways and reprogramming lipid metabolism.

Immunotherapy showed remarkable efficacy in several cancer types. However, the majority of patients do not benefit from immunotherapy. Evaluating tumor heterogeneity and immune status before treatment is key to identifying patients that are more likely to respond to immunotherapy. Demographic characteristics (such as sex, age, and race), immune status, and specific biomarkers all contribute to response to immunotherapy. A comprehensive immunodiagnostic model integrating all these three dimensions by artificial intelligence would provide valuable information for predicting treatment response. Here, we coined the term “immunodiagnosis” to describe the blueprint of the immunodiagnostic model. We illustrated the features that should be included in immunodiagnostic model and the strategy of constructing the immunodiagnostic model. Lastly, we discussed the incorporation of this immunodiagnosis model in clinical practice in hopes of improving the prognosis of tumor immunotherapy.

Background Dilated cardiomyopathy (DCM) is a major cause of heart failure in children. Despite intensive genetic analyses, pathogenic gene variants have not been identified in most patients with DCM, which suggests that cardiomyocytes are not solely responsible for DCM. Cardiac fibroblasts (CFs) are the most abundant cell type in the heart. They have several roles in maintaining cardiac function; however, the pathological role of CFs in DCM remains unknown. Methods and Results Four primary cultured CF cell lines were established from pediatric patients with DCM and compared with 3 CF lines from healthy controls. There were no significant differences in cellular proliferation, adhesion, migration, apoptosis, or myofibroblast activation between DCM CFs compared with healthy CFs. Atomic force microscopy revealed that cellular stiffness, fluidity, and viscosity were not significantly changed in DCM CFs. However, when DCM CFs were cocultured with healthy cardiomyocytes, they deteriorated the contractile and diastolic functions of cardiomyocytes. RNA sequencing revealed markedly different comprehensive gene expression profiles in DCM CFs compared with healthy CFs. Several humoral factors and the extracellular matrix were significantly upregulated or downregulated in DCM CFs. The pathway analysis revealed that extracellular matrix receptor interactions, focal adhesion signaling, Hippo signaling, and transforming growth factor‐β signaling pathways were significantly affected in DCM CFs. In contrast, single‐cell RNA sequencing revealed that there was no specific subpopulation in the DCM CFs that contributed to the alterations in gene expression. Conclusions Although cellular physiological behavior was not altered in DCM CFs, they deteriorated the contractile and diastolic functions of healthy cardiomyocytes through humoral factors and direct cell–cell contact.

Salinity is one of the most common environmental stress factors, which has a substantial influence on the growth, metabolism, and distribution of crustaceans, while transport of ions and water are considered to play important roles in response to salinity stress. The Chinese shrimp (Fenneropenaeus chinensis) is an important shrimp species cultured in northern China and salinity conditions influence its commercial farming significantly. The study aims to elucidate the potential roles of ion-transport related genes Na+/K+-ATPase α subunit (NKAα), cytoplasmic carbonic anhydrase (CAc), and V-type H+-ATPase subunits (VHA-C, VHA-F, and VHA-G), and water channels of aquaporins (AQP3 and AQP4) in F. chinensis under high-salinity stress. The open reading frames (ORFs) of these genes were cloned, validated, and characterized based on blast against the transcriptomic data. Tissue distribution analysis revealed the predominant expression of these genes in the gills. Then, qPCR was used to examine the expression patterns of genes in the post-larvae shrimp and the gills of adult shrimp in response to hyper-osmotic challenges with two salinities (40 and 45). The results showed that the relative expression levels of these genes were all significantly decreased (p

Seed priming has become a practical pre-sowing strategy to deal with abiotic stresses. This study aims to explore the effects of polyethylene glycol (PEG) priming on seed germination and seedling growth of Scutellaria baicalensis Georgi under salt stress. Regardless of seed priming, salt stress significantly inhibited the seed germination and seedling growth of S. baicalensis. PEG priming significantly alleviates the inhibitory effects of salt stress on seed germination and seedling growth when compared to non-priming and water priming. Among all treatments, PEG priming exhibited the highest germination rate, germination potential, seed vigor index, fresh weight, dry weight, and plant length; the highest contents of proline, soluble sugar, and soluble protein; the highest K+/Na+ ratio and relative water content; the highest antioxidant activities and contents; but the lowest H2O2, malondialdehyde (MDA) content, and relative electrical conductivity in response to salt stress. In addition, PEG priming had the highest transcript levels of antioxidant-related genes among all treatments under NaCl stress. Taken together, the results demonstrated that seed priming with PEG could be recommended as an effective practice to enhance the germination and early seedling growth of S. baicalensis under saline conditions.

Joint relational triple extraction is a crucial step in constructing a knowledge graph from unstructured text. Recently, multiple methods have been proposed for extracting relationship triplets. Notably, end-to-end table-filling methods have garnered significant research interest due to their efficient extraction capabilities. However, existing approaches usually generate separate tables for each relationship, which neglects the global correlation between relationships and context, producing a large number of useless blank tables. This problem results in issues of redundant information and sample imbalance. To address these challenges, we propose a novel framework for joint entity and relation extraction based on a single-table filling method. This method incorporates all relationships as prompts within the text sequence and associates entity span information with relationship labels. This approach reduces the generation of redundant information and enhances the extraction capability for overlapping triplets. We utilize the internal and external multi-head tensor fusion approach to generate two sets of table feature vectors. These vectors are subsequently merged to capture a wider range of global information. Experimental results on the NYT and WebNLG datasets demonstrate the effectiveness of our proposed model, which maintains excellent performance, even in complex scenarios involving overlapping triplets.

This study was conducted to evaluate the effects of high salinity combined with stocking density on Litopenaeus vannamei. Three salinity gradients, namely, 28 g/L, 36 g/L, and 44 g/L, and two stocking densities, namely, 300 and 600 shrimp/m3, were used to analyze the synergistic effect of high salinity and stocking density on the growth performance, digestibility, and energy budgets of L. vannamei. The experimental testing period lasted 45 days. The research results showed that a salinity level of 36 g/L was the most suitable salinity level for shrimp growth under both high and low stocking densities. The body weight, specific growth rate, and relative weight gain of the shrimp in the 36 g/L salinity group were significantly higher than those in the other two salinity groups under both high and low stocking densities. The high-density farming group with 600 shrimp/m3 exhibited a significant inhibition of shrimp growth compared to the low-density group under the same salinity conditions. The activities of amylase, lipase, and protease in the high-density-group shrimp gradually decreased with an increase in salinity, and the three digestive enzymes had the same overall effect of changing trends. This indicates that under high-density farming conditions, the increase in salinity is not conducive to the digestive function of shrimps. At the same time, the proportion of respiratory energy to feeding energy gradually decreased in the high-density group and with the increase in salinity. However, under the same salinity conditions, the higher the stocking density, the higher the energy consumed by respiration compared to the low-density group. In addition, the expression of the growth-related gene’s small nuclear ribonucleoprotein polypeptide G (SNRPG) under high stocking density was significantly lower than that in the low-density group at a salinity of 28 g/L, and ribosomal protein L7 (RPL7) expression was also significantly lower under high stocking density than that in the low-density group at a salinity of 44 g/L. The expression levels of molting-related genes retinoid X receptor (RXR), ecdysone receptor (ECR), and ecdysone-induced protein 75 (E75) were significantly higher in the 36 g/L salinity group compared with the other two salinity groups under high-stocking-density treatment. The findings indicate that the synergistic effects of salinity and stocking density have a significant impact on the growth of L. vannamei, and excessive salinity would inhibit its growth in the process of high-density culturing.

Novel Fenton-like catalyst HKUST-1(Cu)/MoS2-3-C with a non-equilibrium-state surface was constructed for selective degradation of phenolic contaminants. Electron-polarized distribution facilitated the formation of σ-Cu-ligand between electron-poor Cu centre and phenolic compounds, which not only enhanced radicals generation but also accelerated the Cu(I)/Cu(II) redox. Meanwhile, ≡Mo–OOSO3− complexes formed by the electron-rich Mo centre and peroxymonosulfate (PMS), could directly oxidize phenolic contaminants with the generation of SO4•−. The radical quenching experiments and EPR tests indicated that both SO4•− and •OH played a dominant role in the reaction. Additionally, O2 could be reduced to O2•− by OVs and subsequently converted into 1O2 over the Mo centre. DFT calculation, FT-IR, and in situ Raman spectra analysis results demonstrated that phenolic compounds and PMS were respectively adsorbed by electron-poor Cu centre and electron-rich Mo centre, favouring the electrons transfer from phenolic contaminants to Mo centre for PMS activation. With synergistic effects of σ-Cu-ligand and ≡Mo–OOSO3− complexes, HKUST-1(Cu)/MoS2-3-C achieved a high degradation rate of phenolic contaminants and utilization efficiency of PMS.

Today, fertility preservation is receiving more attention than ever. Cryopreservation, which preserves ovarian tissue to preserve fertility in young women and reduce the risk of infertility, is currently the most widely practiced. Transplantation, however, is less feasible for women with blood-borne leukemia or cancers with a high risk of ovarian metastasis because of the risk of cancer recurrence. In addition to cryopreservation and re-implantation of embryos, in vitro ovarian organ reconstruction techniques have been considered as an alternative strategy for fertility preservation. In vitro culture of oocytes in vitro Culture, female germ cells induction from pluripotent stem cells (PSC) in vitro, artificial ovary construction, and ovaria-related organoids construction have provided new solutions for fertility preservation, which will therefore maximize the potential for all patients undergoing fertility preservation. In this review, we discussed and thought about the latest ovarian organ function reconstruction techniques in vitro to provide new ideas for future ovarian disease research and fertility preservation of patients with cancer and premature ovarian failure.

Carallia diplopetala (Rhizophoraceae) is an important economic tree species narrowly distributed endemic to East Asia. In this study, We generate the complete chloroplast genome of C. diplopetala using next-generation sequencing technology, which is 162,052 bp in size and consists of a large single copy (LSC) of 89,556 bp and a small single copy (SSC) of 18,814 bp, separated a pair of inverted repeats (IRb and IRa) of 26,841 bp. The overall GC content is 36.4%. A total of 130 genes are annotated, including 83 protein-coding genes, 37 tRNAs, eight rRNAs and two pseudogenes (ψycf1 and ψrps19). The phylogenetic analysis indicated that C. diplopetala and C. brachiate formed a monophyletic clade with strong support and then sister to Pellacalyx yunnanensis. The plastome of C. diplopetala will provide informative genomic resources for further conservation applications.

Abstract Background Necroptosis is a new form of programmed cell death that is associated with cancer initiation, progression, immunity, and chemoresistance. However, the roles of necroptosis-related genes (NRGs) in colorectal cancer (CRC) have not been explored comprehensively. Methods In this study, we obtained NRGs and performed consensus molecular subtyping by “ConsensusClusterPlus” to determine necroptosis-related subtypes in CRC bulk transcriptomic data. The ssGSEA and CIBERSORT algorithms were used to evaluate the relative infiltration levels of different cell types in the tumor microenvironment (TME). Single-cell transcriptomic analysis was performed to confirm classification related to NRGs. NRG_score was developed to predict patients’ survival outcomes with low-throughput validation in a patients’ cohort from Fudan University Shanghai Cancer Center. Results We identified three distinct necroptosis-related classifications (NRCs) with discrepant clinical outcomes and biological functions. Characterization of TME revealed that there were two stable necroptosis-related phenotypes in CRC: a phenotype characterized by few TME cells infiltration but with EMT/TGF-pathways activation, and another phenotype recognized as immune-excluded. NRG_score for predicting survival outcomes was established and its predictive capability was verified. In addition, we found NRCs and NRG_score could be used for patient or drug selection when considering immunotherapy and chemotherapy. Conclusions Based on comprehensive analysis, we revealed the potential roles of NRGs in the TME, and their correlations with clinicopathological parameters and patients’ prognosis in CRC. These findings could enhance our understanding of the biological functions of necroptosis, which thus may aid in prognosis prediction, drug selection, and therapeutics development.

Abstract Limited previous studies focused on the death and progression risk stratification of colorectal cancer (CRC) lung metastasis patients. The aim of this study is to construct a nomogram model combing machine learning-pathomics, radiomics features, Immunoscore and clinical factors to predict the postoperative outcome of CRC patients with lung metastasis. In this study, a total of 103 CRC patients having metastases limited to lung and undergoing radical lung resection were identified. Patch-level convolutional neural network training in weakly supervised manner was used to perform whole slides histopathological images survival analysis. Synthetic minority oversampling technique and support vector machine classifier were used to identify radiomics features and build predictive signature. The Immunoscore for each patient was calculated from the density of CD3+ and CD8+ cells at the invasive margin and the center of metastatic tumor which were assessed on consecutive sections of automated digital pathology. Finally, pathomics and radiomics signatures were successfully developed to predict the overall survival (OS) and disease free survival (DFS) of patients. The predicted pathomics and radiomics scores are negatively correlated with Immunoscore and they are three independent prognostic factors for OS and DFS prediction. The combined nomogram showed outstanding performance in predicting OS (AUC = 0.860) and DFS (AUC = 0.875). The calibration curve and decision curve analysis demonstrated the considerable clinical usefulness of the combined nomogram. Taken together, the developed nomogram model consisting of machine learning-pathomics signature, radiomics signature, Immunoscore and clinical features could be reliable in predicting postoperative OS and DFS of colorectal lung metastasis patients.

Summary: Background: Early detection and prognosis prediction of colorectal cancer (CRC) can significantly reduce CRC-related mortality. Recently, circulating tumour DNA (ctDNA) methylation has shown good application foreground in the early detection and prognosis prediction of multiple tumours. Methods: This multicentre cohort study evaluated ctDNA methylation haplotype patterns based on archived plasma samples (collected between 2010 and 2018) from 1138 individuals at two medical centres: Fudan University Shanghai Cancer Center (Shanghai, China) and Southern Medical University Nanfang Hospital (Guangzhou, Guangdong, China), including 366 healthy individuals, 182 patients with advanced adenoma (AA), and 590 patients with CRC. Samples were processed using the ColonES assay, a targeted bisulfite sequencing method that detects ctDNA methylation haplotype patterns in 191 genomic regions. Among these 1138 samples, 748 were used to develop a classification model, and 390 served as a blinded cohort for independent validation. The study is registered at https://register.clinicaltrials.gov with the unique identifier NCT03737591. Results: The model obtained from unblinded samples discriminated patients with CRC or AA from normal controls with high accuracy. In the blinded validation set, the ColonES assay achieved sensitivity values of 79.0% (95% confidence interval (CI), 66%–88%) in AA patients and 86.6% (95% CI, 81%–91%) in CRC patients with a specificity of 88.1% (95% CI, 81%–93%) in healthy individuals. The model area under the curve (AUC) for the blinded validation set was 0.903 for AA samples and 0.937 for CRC samples. Additionally, the prognosis of patients with high preoperative ctDNA methylation levels was worse than that of patients with low ctDNA methylation levels (p = 0.001 for relapse-free survival and p = 0.004 for overall survival). Interpretation: We successfully developed and validated an accurate, noninvasive detection method based on ctDNA methylation haplotype patterns that may enable early detection and prognosis prediction for CRC. Funding: The Grant of National Natural Science Foundation of China (No.81871958), National Natural Science Foundation of China (No. 82203215), Shanghai Science and Technology Committee (No. 19140902100), Scientific Research Fund of Fudan University (No.IDF159052), Shanghai Municipal Health Commission (SHWJRS 2021-99), and Shanghai Sailing Program (22YF1408800).

This study was conducted to evaluate the effect of flavor on reproductive performance and fecal microbiota of sows during late gestation and lactation. A total of 20 healthy Yorkshire sows were fed a corn-soybean basal diet unsupplemented or supplemented with 0.1% flavor compound from d 90 of gestation to 25 d post-farrowing, and then the piglets were weaned. The reproductive performance and the fecal microbiota of sows were analyzed. Compared with the controls, flavor supplementation in maternal diets increased (P 0.05). The 16S rRNA analysis showed that flavor supplementation significantly increased the abundance of Phascolarctobacterium (P

BackgroundThe field of rehabilitation medicine plays an essential role in the comprehensive management of osteoporosis and its consequences. The benefits of therapeutic exercise are increasingly being recognized in this area, which receives an increasing number of publications. this study was designed to comprehensively identify collaborative networks, parse and track research trends, spotlight present hotspots, and accurately predict frontiers and focus on the health topics related to osteoporosis rehabilitation.MethodsThis research adopted computer retrieval of osteoporosis rehabilitation-related research published in the Web of Science Core Collection (WoSCC) from inception to June 14, 2022. The bibliometric visualization and comparative analysis involving countries, institutions, journals, authors, references, and keywords were performed using the CiteSpace and VOSviewer software.ResultsA total of 3,268 articles were included, and the number of articles published each year has demonstrated a steady increase. The United States and the University of Melbourne were the highest productive country and institution, with 1,325 and 87 articles, respectively. The journal of osteoporosis international has published the greatest number of articles, with 221 publications, and the journal of bone and mineral research ranked first in the co-citation counts (cited by 11,792 times). The most productive and highly-cited authors were Heinonen A and Cummings S, with 35 publications and 680 citations.ConclusionsAt present, “physical activity,” “weight bearing exercise,” “muscle strength,” “whole body vibration,” “postmenopausal women,” “older women,” children, men are the noteworthy research hot topics. Future research that focus on the major modes and parameters of physical activity/exercise for osteoporosis (including whole body vibration, weight bearing exercises, resistance training), targeted multicomponent training regimens, rehabilitation therapy for postmenopausal women, older women, children and men, osteoporosis related-sarcopenia and fractures, and mesenchymal stem cells are becoming frontiers and focus on the health topics related to osteoporosis rehabilitation in the upcoming years, which are worthy of further exploration.

It is well established that forest type can have a profound impact on soil physicochemical properties but the associated changes in soil microbial communities and the mechanisms by which soil quality is improved by various plantations are not fully understood. In this study, soil physicochemical properties and microbial and enzyme activities were investigated in four forest types–Castanopsis hystrix pure forests (CHPF), C. hystrix–Pinus elliottii mixed forests (CHPEF), C. hystrix–Michelia macclurei mixed forests (CHMMF), and C. hystrix–Mytilaria laosensis mixed forests (CHMLF) in the subtropical region of China. The purpose of this study was to assess the effects of afforestation types on characteristics of soil–its physical, chemical, and biological properties. The results showed that the contents of soil total organic carbon (TOC), soil total nitrogen (TN), microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN) were significantly improved in both CHMMF and CHMLF mixed forest stands when compared to the CHPF pure stand. Soil enzyme activities were enhanced in the mixed forests. In particular, high phosphatase activity was observed in CHMLF stands, leading to the transformation of soil phosphorus to available phosphorus in this forest type. Our study demonstrated that the broad–leaved mixed forests, but not coniferous mixed forests, could significantly improve soil quality in the study region. Our research provides a scientific insight into the promotion of vegetation restoration and plantation forest management in plantation regions of subtropical areas.

Abstract Background Different endometrial patterns have an important effect on the relationship between endometrial thickness (EMT) and clinical pregnancy rate. There is a significant difference in age, selection of cycle protocols, and clinical pregnancy rates among four groups with diverse endometrial patterns. Methods This retrospective study aimed to assess the association between EMT on human chorionic gonadotropin (HCG) administration day and the clinical outcome of fresh in vitro fertilization (IVF). The 5th, 50th, and 95th percentiles for EMT were determined as 8, 11, and 14 mm, respectively. Patients were sub-divided into four groups based on their EMT in different endometrial patterns (Group 1: 11 and ≤ 14 mm; Group 4: > 14 mm). We divided patients into three groups based on their endometrial pattern and evaluated the correlation between EMT and clinical pregnancy rate. Results We found a positive correlation between pregnancy rates and EMT in all endometrial patterns. Multiple logistic regression analysis proved age, duration of infertility, cycle protocols, number of embryos transferred, progesterone on HCG day, endometrial patterns, and EMT have significant effects on clinical pregnancy rates. Meanwhile, there was a significant difference in age, selection of cycle protocols, and clinical pregnancy rates among four groups with diverse endometrial patterns. Conclusions Different endometrial patterns have an important effect on the relationship between EMT and clinical pregnancy rate.

Water management of the gas diffusion layer (GDL) is crucial to the performance of proton exchange membrane fuel cells (PEMFCs). Appropriate water management ensures efficient transport of reactive gases and maintains wetting of the proton exchange membrane to enhance proton conduction. In this paper, a two-dimensional pseudo-potential multiphase lattice Boltzmann model is developed to study liquid water transport within the GDL. Liquid water transport from the GDL to the gas channel is the focus, and the effect of fiber anisotropy and compression on water management is evaluated. The results show that the fiber distribution approximately perpendicular to the rib reduces liquid water saturation within the GDL. Compression significantly changes the microstructure of the GDL under the ribs, which facilitates the formation of liquid water transport pathways under the gas channel, and the increase in the compression ratio leads to a decrease in liquid water saturation. The performed microstructure analysis and the pore-scale two-phase behavior simulation study comprise a promising technique for optimizing liquid water transport within the GDL.

Aquaporins (AQPs) are major intrinsic proteins that facilitate the transport of water, small solutes, and ions through membranes. In mammals, the classical aquaporin AQP4 plays a central role in the preservation of central nervous system (CNS) water homeostasis. Litopenaeus vannamei is a typical euryhaline crustacean, with a salinity tolerance range of 0.5–78. Compared to those reared at low-salinity, shrimps cultured at high-salinity have better taste and qualities, but slower growth, lower product yield, and higher mortality. Thus, there is an urgent need to research the osmoregulation of L. vannamei under high-salinity. Previous studies mainly focus on the osmoregulation of gill and hepatopancreas, whereas there is a lack of research on the osmoregulatory roles of CNS in L. vannamei. In the current study, we first presented another two classical AQPs from L. vannamei, of which the arthropod-specific big brain aquaporin (LvBib) was expressed as C-terminal splice variants (LvBib_L and LvBib_S), and the aquaporin-like protein (LvAqpl) was a new type of aquaporin in crustaceans. Tissue distribution revealed that LvAqp4, LvAqpl, and LvBib_L were mostly expressed in the CNS of brain and thoracic ganglion. Then, the expression pattern of aquaporins in brain and thoracic ganglion were examined under both acute and chronic high-salinity stresses. The LvAqpl was found to be down-regulated in both tissues in the two experiments; LvAqp4 was elevated in both tissues under acute stress, whereas it was decreased in the thoracic ganglion during early periods of adaption to high-salinity; LvBib_L was up-regulated in brain but down-regulated in thoracic ganglion under acute stress, whereas it showed the opposite expression pattern during chronic stress. The results suggest that these aquaporins have an important role in the CNS response to high-salinity challenge. Our study provides a base for future mechanistic studies on the role of classical aquaporins in osmoregulation.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Tumor metastasis accounts for the majority of cancer-related deaths; it is therefore important to develop preclinical models that faithfully recapitulate disease progression. Here, we generated paired organoids derived from primary tumors and matched liver metastases in the same colorectal cancer (CRC) patients. Despite the fact that paired organoids exhibit comparable gene expression and cell morphology, organoids from metastatic lesions demonstrate more aggressive phenotypes, tumorigenesis, and metastatic capacity than those from primary lesions. Transcriptional analyses of the paired organoids reveal signature genes and pathways altered during the progression of CRC, including SOX2. Further study shows that inducible knockdown of SOX2 attenuated invasion, proliferation, and liver metastasis outgrowth. Taken together, we use patient-derived paired primary and metastatic cancer organoids to model CRC metastasis and illustrate that SOX2 is associated with CRC progression and may serve as a potential prognostic biomarker and therapeutic target of CRC.

Abstract Background Radiation therapy is a main treatment option for cancer. Due to normal tissue toxicity, radiosensitizers are commonly used to enhance RT. In particular, heavy metal or high-Z materials, such as gold nanoparticles, have been investigated as radiosensitizers. So far, however, the related studies have been focused on spherical gold nanoparticles. In this study, we assessed the potential of ultra-thin gold nanowires as a radiosensitizer, which is the first time. Methods Gold nanowires were synthesized by the reduction of HAuCl4 in hexane. The as-synthesized gold nanowires were then coated with a layer of PEGylated phospholipid to be rendered soluble in water. Spherical gold nanoparticles coated with the same phospholipid were also synthesized as a comparison. Gold nanowires and gold nanospheres were first tested in solutions for their ability to enhance radical production under irradiation. They were then incubated with 4T1 cells to assess whether they could elevate cell oxidative stress under irradiation. Lastly, gold nanowires and gold nanoparticles were intratumorally injected into a 4T1 xenograft model, followed by irradiation applied to tumors (3 Gy/per day for three days). Tumor growth was monitored and compared. Results Our studies showed that gold nanowires are superior to gold nanospheres in enhancing radical production under X-ray radiation. In vitro analysis found that the presence of gold nanowires caused elevated lipid peroxidation and intracellular oxidative stress under radiation. When tested in vivo, gold nanowires plus irradiation led to better tumor suppression than gold nanospheres plus radiation. Moreover, gold nanowires were found to be gradually reduced to shorter nanowires by glutathione, which may benefit fractionated radiation. Conclusion Our studies suggest that gold nanowires are a promising type of radiosensitizer that can be safely injected into tumors to enhance radiotherapy. While the current study was conducted in a breast cancer model, the approach can be extended to the treatment of other cancer types.

Vehicle emissions calculation methods mostly use ownership information or annual road monitoring data as the activity level to calculate air pollutant emissions, but it is hard to reflect either the emissions intensity under different conditions or the spatiotemporal characteristics in various sections based on such approaches. This paper presents a method based on the Macroscopic Fundamental Diagram and real-time traffic data to calculate vehicle emissions, which could reflect the operation conditions and emission characteristics of vehicles. Following the ‘Technical Guide for the Compiling of Road Vehicle Air Pollutant Emissions Inventories’, the emissions of three roads with different lane numbers and road grades in Beijing were estimated and verified using this method. Compared with monitoring data, the average deviations of the traffic flow on the Fifth Expressway, Jingfu National Highway, and Jingzhou Provincial Highway were −25.5%, −26.5%, and −13.4%, respectively, and the average deviations of nitrogen oxides emissions were −27.7%, −12.9%, and −12%, respectively. This method showed good application potentials to construct the emissions inventory applied to the block-scale model and analyze the spatiotemporal distribution characteristics of motor vehicle emissions in urban areas.

Abstract Accurate identification of patients with poor prognosis after radical surgery is essential for clinical management of colon cancer. Thus, we aimed to develop death and relapse specific radiomics signatures to individually estimate overall survival (OS) and relapse free survival (RFS) of colon cancer patients. In this study, 701 stage I‐III colon cancer patients were identified from Fudan University Shanghai Cancer Center. A total of 647 three‐dimensional features were extracted from computed tomography images. LASSO Cox was used to identify the significantly death‐ and relapse‐associated features and to build death and relapse specific radiomics signatures, respectively. A total of 13 death‐specific and 26 relapse‐specific features were identified from 647 screened radiomics features. The developed signatures can divide patients into two groups with significantly different death (Hazard Ratio (HR): 3.053; 95% CI, 1.78‐5.23; P

Abstract Background It is critical for determining the optimum therapeutic solutions for T1‐2 colorectal cancer (CRC) to accurately predict lymph node metastasis (LNM) status. The purpose of the present study is to establish and verify a nomogram to predict LNM status in T1‐2 CRCs. Methods A total of 16 600 T1‐2 CRC patients were enrolled and classified into the training, internal validation, and external validation cohorts. The independent predictive parameters were determined by univariate and multivariate analyses to develop a nomogram to predict the probability of LNM status. The calibration curve, the area under the receiver operating characteristic curve (AUROC), and decision curve analysis (DCA) were used to evaluate the performance of the nomogram, and an external verification cohort was to verify the applicability of the nomogram. Results Seven independent predictors of LNM in T1‐2 CRC were identified in the multivariable analysis, including age, tumor site, tumor grade, perineural invasion, preoperative carcinoembryonic antigen, clinical assessment of LNM, and T stage. A nomogram incorporating the seven predictors was constructed. The nomogram yielded good discrimination and calibration, with AUROCs of 0.72 (95% confidence interval [CI]: 0.70‐0.75), 0.70 (95% CI: 0.67‐0.74), and 0.74 (95% CI: 0.71‐0.79) in the training, internal validation, and external validation cohorts, respectively. DCA showed that the predictive scoring system had high clinical application value. Conclusions We proposed a novel predictive model for LNM in T1‐2 CRC patients to assist physicians in making treatment decisions. The nomogram is advantageous for tailoring therapy in T1‐2 CRC patients.

Abstract Background Low expression of FOXE1, a member of Forkhead box (FOX) transcription factor family that plays vital roles in cancers, contributes to poor prognosis of colorectal cancer (CRC) patients. However, the underlying mechanism remains unclear. Materials and methods The effects of FOXE1 on the growth of colon cancer cells and the expression of glycolytic enzymes were investigated in vitro and in vivo. Molecular biological experiments were used to reveal the underlying mechanisms of altered aerobic glycolysis. CRC tissue specimens were used to determine the clinical association of ectopic metabolism caused by dysregulated FOXE1. Results FOXE1 is highly expressed in normal colon tissues compared with cancer tissues and low expression of FOXE1 is significantly associated with poor prognosis of CRC patients. Silencing FOXE1 in CRC cell lines dramatically enhanced cell proliferation and colony formation and promoted glucose consumption and lactate production, while enforced expression of FOXE1 manifested the opposite effects. Mechanistically, FOXE1 bound directly to the promoter region of HK2 and negatively regulated its transcription. Furthermore, the expression of FOXE1 in CRC tissues was negatively correlated with that of HK2. Conclusion FOXE1 functions as a critical tumor suppressor in regulating tumor growth and glycolysis via suppressing HK2 in CRC.