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Molecular recognition was utilized to fabricate bioinspired calcium phosphate (Ca-P) coating on bioabsorbable magnesium alloys through small biomolecules such as Vitamin C (VC). Ca-P and VC hybrid coating (Ca-PVC) was successfully fabricated on AZ31 Mg alloy. The surface morphology and chemical composition of the coatings were investigated using SEM, XRD, and FTIR together with XPS. The results showed that the Ca-PVC coating was composed of bamboo leaf-like Ca-P particles with a thickness of about three times that of the Ca-P coating. The surface roughness of the Ca-PVC coating (1.12 ± 0.12 μm) was lower than that (3.14 ± 1.93 μm) of Ca-P coating, suggesting the formation of refined Ca-P particles resulting from the VC addition. The corrosion resistance of the coated samples was characterized via electrochemical polarization, impedance spectroscopy, and immersion hydrogen evolution tests. The cell toxicity of the coated samples was evaluated utilizing mouse MC3T3-E1 pre-osteoblasts. The charge transfer resistance (Rct) of the Ca-PVC coated alloy increased as compared to the bare and Ca-P coated alloy samples. The Ca-PVC coated alloy exhibited minimal corrosion current density (1.36 × 10−6 A cm−2), which is one order of magnitude lower in comparison to that of the Ca-P coated alloy. These results confirm that VC addition greatly enhanced the coating resistance on AZ31 Mg alloy. It was also noticed that the Ca-PVC coated samples rapidly induced the formation of apatite after immersion in Hank's solution. VC was mainly transformed to L-Threonic acid, which facilitated the nucleation process of the Ca-PVC coating and significantly increased the thickness, density, and bonding strength of the coating. With enhanced corrosion resistance property and excellent biocompatibility, Ca-PVC coating has great potential for application in biodegradable Mg-based alloys.

Trimethylamine N-oxide (TMAO) has attracted interest because of its association with cardiovascular disease and diabetes, and evidence for the beneficial effects of TMAO is accumulating. This study investigates the role of TMAO in improving exercise performance and elucidates the underlying molecular mechanisms. Using C2C12 cells, we established an oxidative stress model and administered TMAO treatment. Our results indicate that TMAO significantly protects myoblasts from oxidative stress-induced damage by increasing the expression of Nrf2, heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase (NQO1), and catalase (CAT). In particular, suppression of Nrf2 resulted in a loss of the protective effects of TMAO and a significant decrease in the expression levels of Nrf2, HO-1, and NQO1. In addition, we evaluated the effects of TMAO in an exhaustive swimming test in mice. TMAO treatment significantly prolonged swimming endurance, increased glutathione and taurine levels, enhanced glutathione peroxidase activity, and increased the expression of Nrf2 and its downstream antioxidant genes, including HO-1, NQO1, and CAT, in skeletal muscle. These findings underscore the potential of TMAO to counteract exercise-induced oxidative stress. This research provides new insights into the ability of TMAO to alleviate exercise-induced oxidative stress via the Nrf2 signaling pathway, providing a valuable framework for the development of sports nutrition supplements aimed at mitigating oxidative stress.

Abstract Background Within the class Enoplea, the earliest-branching lineages in the phylum Nematoda, the relatively highly conserved ancestral mitochondrial architecture of Trichinellida is in stark contrast to the rapidly evolving architecture of Dorylaimida and Mermithida. To better understand the evolution of mitogenomic architecture in this lineage, we sequenced the mitogenome of a fish parasite Pseudocapillaria tomentosa (Trichinellida: Capillariidae) and compared it to all available enoplean mitogenomes. Results P. tomentosa exhibited highly reduced noncoding regions (the largest was 98 bp), and a unique base composition among the Enoplea. We attributed the latter to the inverted GC skew (0.08) in comparison to the ancestral skew in Trichinellidae (-0.43 to -0.37). Capillariidae, Trichuridae and Longidoridae (Dorylaimida) generally exhibited low negative or low positive skews (-0.1 to 0.1), whereas Mermithidae exhibited fully inverted low skews (0 to 0.05). This is indicative of inversions in the strand replication order or otherwise disrupted replication mechanism in the lineages with reduced/inverted skews. Among the Trichinellida, Trichinellidae and Trichuridae have almost perfectly conserved architecture, whereas Capillariidae exhibit multiple rearrangements of tRNA genes. In contrast, Mermithidae (Mermithida) and Longidoridae (Dorylaimida) exhibit almost no similarity to the ancestral architecture. Conclusions Longidoridae exhibited more rearranged mitogenomic architecture than the hypervariable Mermithidae. Similar to the Chromadorea, the evolution of mitochondrial architecture in enoplean nematodes exhibits a strong discontinuity: lineages possessing a mostly conserved architecture over tens of millions of years are interspersed with lineages exhibiting architectural hypervariability. As Longidoridae also have some of the smallest metazoan mitochondrial genomes, they contradict the prediction that compact mitogenomes should be structurally stable. Lineages exhibiting inverted skews appear to represent the intermediate phase between the Trichinellidae (ancestral) and fully derived skews in Chromadorean mitogenomes (GC skews = 0.18 to 0.64). Multiple lines of evidence (CAT-GTR analysis in our study, a majority of previous mitogenomic results, and skew disruption scenarios) support the Dorylaimia split into two sister-clades: Dorylaimida + Mermithida and Trichinellida. However, skew inversions produce strong base composition biases, which can hamper phylogenetic and other evolutionary studies, so enoplean mitogenomes have to be used with utmost care in evolutionary studies.

Abstract The Medium‐Energy Electron Detector (MEED), a space weather monitoring instrument on the Fengyun‐3E (FY‐3E) satellite, is introduced in this paper. The MEED utilizes pin‐hole imaging technology on low‐orbit satellites for medium‐energy electron detection. Two orthogonal sensor heads enable the MEED to measure electrons from 18 directions simultaneously in the energy range of 30–600 keV (divided into eight exponentially distributed energy channels). The instrument has a ∼12° angular resolution and covers two 180° × 30° fields of view. With the magnetometer onboard the same satellite, the pitch angle distribution of medium‐energy electrons can be obtained with good angular resolution. This paper presents the design principle, ground calibration results, and preliminary on‐orbit test results of the FY‐3E MEED. The on‐orbit test results show that the medium‐energy electron fluxes, geographical distribution, energy spectrum, and pitch angle observed by the MEED are in agreement with the expected results. The MEED provides a new method to observe the low‐orbit energetic electron radiation environment from the FY‐3E satellite. Its successful in‐orbit operation will enable the theoretical study of radiation belts and improve space weather research.

Abstract Background Synovial sarcoma (SS) is a type of soft tissue sarcoma (STS) of undetermined tissue origin, which is characterized by the recurrent pathognomonic chromosomal translocation t (X;18)(p11.2; q11.2). Studies have shown that SS is a malignant tumor originating from cancer stem cells or pluripotent mesenchymal stem cells and may be related to fusion genes. In addition, some studies have indicated that the induction of epithelial–mesenchymal transition (EMT) via the TGF-β1/Smad signaling pathway leads to SS metastasis. Methods We analyzed the effects of SYT-SSX1 on the stemness of SS cells via TGF-β1/Smad signaling in vitro. The SYT-SSX1 fusion gene high expression cell was constructed by lentiviral stable transfer technology. SYT-SSX1 and SW982 cells were cultured and tested for sphere-forming ability. The transwell migration assay and flow cytometry were used to assess the migration ability of the sphere cells as well as the expression of CSC-related markers. We treated SYT-SSX1 cells with rhTGF-β1 (a recombinant agent of the TGF-β1 signaling pathway) and SB431542 and observed morphological changes. A CCK-8 experiment and a western blot (WB) experiment were conducted to detect the expression of TGF-β1 signaling pathway- and EMT-related proteins after treatment. The SYT-SSX1 cells were then cultured and their ability to form spheres was tested. Flow cytometry, WB, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of CSC surface markers on SYT-SSX1 sphere cells. Results It was found that SYT-SSX1 has stronger sphere-forming ability, migration ability, and higher expression of CSC-related molecules than SW982 cells. Through treating SYT-SSX1 and SW982 cells with rhTGF-β1 and SB431542, we found that TGF-β1 enhanced the proliferation of cells, induced EMT, and that TGF-β1 enhanced the characteristics of tumor stem cells. Conclusions Our results suggest that SYT-SSX1 enhances invasiveness and maintains stemness in SS cells via TGF-β1/Smad signaling. These findings reveal an effective way to potentially improve the prognosis of patients with SS by eliminating the characteristics of cancer stem cells (CSCs) during treatment.

Abstract High-grade serous ovarian cancer (HGSOC) is a common and lethal cancer of the female reproductive system. Long non-coding RNAs (lncRNAs) are aberrantly expressed in various cancers and play crucial roles in tumour progression. However, their function and molecular mechanism in HGSOC remain largely unknown. Based on public databases and bioinformatics analyses, the overexpression of lncRNA CTBP1-DT in HGSOC tissues was detected and validated in a cohort of HGSOC tissues. High expression of lncRNA CTBP1-DT was associated with poor prognosis and was an independent risk factor for survival. Overexpression of lncRNA CTBP1-DT promoted malignant biological behaviour of HGSOC cells, whereas its depletion induced growth arrest of HGSOC cells by vitro and in vivo assays. Mechanistically, lncRNA CTBP1-DT could competitively bind to miR-188-5p to protect MAP3K3 from degradation. Moreover, our results revealed that ETV5 could specifically interact with the promoter of lncRNA CTBP1-DT and activate its transcription. Collectively, these results reveal a novel ETV5/lncRNA CTBP1-DT/miR-188-5p/MAP3K3 pathway for HGSOC progression and suggest that lncRNA CTBP1-DT might be a potential biomarker and therapeutic target for HGSOC.

Abstract Phylogenetic analysis has entered the genomics (multilocus) era. For less experienced researchers, conquering the large number of software programs required for a multilocus‐based phylogenetic reconstruction can be somewhat daunting and time‐consuming. PhyloSuite, a software with a user‐friendly GUI, was designed to make this process more accessible by integrating multiple software programs needed for multilocus and single‐gene phylogenies and further streamlining the whole process. In this protocol, we aim to explain how to conduct each step of the phylogenetic pipeline and tree‐based analyses in PhyloSuite. We also present a new version of PhyloSuite (v1.2.3), wherein we fixed some bugs, made some optimizations, and introduced some new functions, including a number of tree‐based analyses, such as signal‐to‐noise calculation, saturation analysis, spurious species identification, and etc. The step‐by‐step protocol includes background information (i.e., what the step does), reasons (i.e., why do the step), and operations (i.e., how to do it). This protocol will help researchers quick‐start their way through the multilocus phylogenetic analysis, especially those interested in conducting organelle‐based analyses.

Background and aims: Improved mortality prediction among intensive care unit (ICU) inpatients is a valuable and challenging task. Limited clinical data, especially with appropriate labels, are an important element restricting accurate predictions. Generative adversarial networks (GANs) are excellent generative models and have shown great potential for data simulation. However, there have been no relevant studies using GANs to predict mortality among ICU inpatients. In this study, we aim to evaluate the predictive performance of a variant of GAN called conditional medical GAN (c-med GAN) compared with some baseline models, including simplified acute physiology score II (SAPS II), support vector machine (SVM), and multilayer perceptron (MLP). Methods: Data from a publicly available intensive care database, the Medical Information Mart for Intensive Care III (MIMIC-III) database (v1.4), were included in this study. The area under the precision-recall curve (PR-AUC), area under the receiver operating characteristic curve (ROC-AUC), and F1 score were used to evaluate the predictive performance. In addition, the size of the dataset was artificially reduced, and the performance of the c-med GAN was compared in different size datasets. Results: The results showed that c-med GAN achieves the best PR-AUC, ROC-AUC, and F1 score compared with SAPS II, SVM, and MLP when training in the full MIMIC-III dataset. When the size of the dataset was reduced, the prediction performances of both MLP and c-med GAN were affected. However, the c-med GAN still outperformed MLP on smaller datasets and had less degradation. Conclusion: The prediction of in-hospital mortality based on the c-med GAN for ICU patients showed better performance than the baseline models. Despite some inadequacies, this model may have a promising future in clinical applications which will be explored by further research.

Background and aims: Accurately predicting length of stay (LOS) is considered a challenging task for health care systems globally. In previous studies on LOS range prediction, researchers commonly pre-classified the LOS ranges, which were the same for all patients in the same classification, and then utilized a classifier for prediction. In this study, we innovatively aimed to predict the specific LOS range for each patient (the LOS range was different for each patient). Methods: In the modified deep neural network (DNN), the overall sample error (root mean square error (RMSE) method), the estimated sample error (ERRpred method), the probability distribution with different loss functions (Dispred_Loss1, Dispred_Loss2, and Dispred_Loss3 method), and the generative adversarial networks (WGAN-GP for LOS method) are used for LOS range prediction. The Medical Information Mart for Intensive Care III (MIMIC-III) database is used to validate these methods. Results: The RMSE method is convenient for LOS range prediction, but the predicted ranges are all consistent in the same batch of samples. The ERRpred method can achieve better prediction results in samples with low errors. However, the prediction effect is worse in samples with larger errors. The Dispred_Loss1 method encounters a training instability problem. The Dispred_Loss2 and Dispred_Loss3 methods perform well in making predictions. Although WGAN-GP for LOS method does not show a substantial advantage over other methods, this method might have the potential to improve the predictive performance. Conclusion: The results show that it is possible to achieve an acceptable accurate LOS range prediction through a reasonable model design, which may help physicians in the clinic.

Abstract Background ETS transcription factors are known to act as either positive or negative regulators of the expression of genes involved in various biological processes. It was reported that ETS variant transcription factor 5 (ETV5), a key member of the ETS family, mainly plays a role as an potential oncogene in various malignant tumors. However, the role and mechanism of ETV5 in high-grade serous ovarian cancer (HGSOC) have not been elucidated. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to detect ETV5 messenger ribonucleic acid (mRNA) expression in 87 HGSOC tissues and 35 normal fallopian tube tissues. Western blotting and qRT-PCR were used to detect the protein and mRNA expression of ETV5 in six ovarian cancer (OC) and human embryonic cell lines. Knockdown or overexpression of ETV5 in HGSOC cell lines, Cell Counting Kit-8, colony formation, and transwell assays were used to detect HGSOC cell proliferation, invasion, and migration capabilities. The chi-square test was used to analyze the clinicopathological characteristics of HGSOC patients. Survival analysis was performed using the Kaplan-Meier method, and the log-rank test was used to analyze the correlation between ETV5 expression and HGSOC patient prognosis. Univariate and multivariate analyses using the Cox regression model were conducted to determine the independent significance of relevant clinical covariates. Results Bioinformatic analysis demonstrated that ETV5 expression was significantly upregulated in OC (p

Abstract Background The differential diagnosis of endometrial stromal tumor (EST) and uterine cellular leiomyoma (CL) remains a challenge in clinical practice, especially low grade endometrial stromal sarcoma (ESS) and CL, suggesting the need for novel immunomarkers panels for differential diagnosis. Interferon-induced transmembrane protein 1 (IFITM1) is a novel immunomarker for endometrial stromal cells, h-caldesmon is an immunomarker for smooth muscle cells and has a higher specificity than smooth muscle actin (SMA). So this study aimed to evaluate whether IFITM1, cluster of differentiation 10(CD10), SMA, and h-caldesmon are useful biomarker combinations for the differential diagnosis of EST and CL. Methods Tissue microarrays were used to detect IFITM1, CD10, SMA, and h-caldesmon immunohistochemical staining in 30 EST and 33 CL cases. Results The expressions of IFITM1 and CD10 were high in EST (86.7 and 63.3%, respectively) but low in CL (18.2 and 21.2%), whereas those of h-caldesmon and SMA were high in CL (87.9 and 100%) and low in EST (6.9 and 40%). In diagnosing EST, IFITM1 shows better sensitivity and specificity (86.7 and 81.8%, respectively) than CD10 (63.3 and 78.8%). The specificity of h-caldesmon in diagnosing CL was significantly higher (93.1%) than that of SMA (60%). When all four antibodies were combined for the differential diagnosis, the area-under-the-curve (AUC) predictive value was 0.995. The best combination for diagnosing EST was IFITM1 (+) or CD10 (+) and h-caldesmon (−) (sensitivity 86.7%, specificity 93.9%). Conclusion The best combination for diagnosing CL were h-caldesmon (+) and SMA (+) (sensitivity 87.9%, specificity 100%). IFITM1, CD10, SMA, and h-caldesmon are a good combination for the differential diagnosis of EST and CL.

Selenium is recognized as an essential element for human health and enters human body mainly via diet. Selenium is a key constituent in selenoproteins, which exert essential biological functions, including antioxidant and anti-inflammatory effects. Several selenoproteins including glutathione peroxidases, selenoprotein P and selenoprotein S are known to play roles in the regulation of type 2 diabetes. Although there is a close association between certain selenoproteins with glucose metabolism or insulin resistance, the relationship between selenium and type 2 diabetes is complex and remains uncertain. Here we review recent advances in the field with an emphasis on roles of selenium on metabolism and type 2 diabetes. Understanding the association between selenium and type 2 diabetes is important for developing clinical practice guidelines, establishing and implementing effective public health policies, and ultimately combating relative health issues.

Summary: The metallic central magnetic axes in high-nucleation clusters with complex structural connections tend to be disorganized and cancel each other out. Therefore, high-nucleation clusters cannot easily exhibit single-molecule magnets (SMMs) behaviors. Herein, we select a triple-core building block (Dy3K2, 1) and use linked diamagnetic alkali metal to form an open, spherical, high-nucleation cluster Dy12Na6 (3) with SMM behavior. Furthermore, by changing the reaction conditions, Dy6K2 (2) formed by linking two Dy3 by K(I) is obtained. High-resolution electrospray mass spectrometry of clusters 1–3 effectively captures the building block Dy3, and clusters 1 and 3 and Dy3 have high stability even with the increase in ion source energy. To the best of our knowledge, this is the first time that an SMM based on a high-nucleation cluster has been obtained by connecting magnetic primitives via diamagnetic metal ions. Dy12K6 is currently the highest nuclear ns-4f heterometallic SMM.

Dactylogyrid is the common parasite on the gills of goldfish (Carassius auratus). Seasonal dynamics of the dactylogyrids on goldfish were investigated from March 2011 to February 2012 in the Liangzi Lake and a fish pond in Shishou, China. Six Dactylogyrus species were found, i.e. D. vastator, D. intermedius, D. arcuatus, D. baueri, D. formosus and D. inexpectatus. The highest mean abundance was recorded for D. arcuatus (4.39) on the wild goldfish, while the highest for D. vastator (0.27) on the farmed goldfish. In Liangzi Lake, except for D. inexpectatus with low infection, prevalence and mean abundance of the other five species of Dactylogyrus exhibited significant seasonal changes (P

K-Ras is a well-studied oncogene, and its mutation is frequently found in epithelial cancers like pancreas, lung, and colorectal cancers. Cancer cells harboring K-Ras mutations are difficult to treat due to the drug resistance and metastasis properties. Cancer stem cells (CSCs) are believed the major cause of chemotherapeutic resistance and responsible for tumor recurrence and metastasis. But how K-Ras mutation affects CSCs and inflammation is not clear. Here, we compared two colon cancer cell lines, HCT-116 and HT-29, with the former being K-RasG13D mutant and the latter being wildtype. We found that HCT-116 cells treated with a K-Ras mutation inhibitor S7333 formed significantly more tumor spheroids than the untreated control, while the wild type of HT-29 cells remained unchanged. However, the size of tumor spheroids was smaller than the untreated controls, indicating their proliferation was suppressed after S7333 treatment. Consistent with this, the expressions of stem genes Lgr5 and CD133 significantly increased and the expression of self-renewal gene TGF-β1 also increased. The flow cytometry analysis indicated that the expression of stem surface marker CD133 increased in the treated HCT-116 cells. To understand the pathway through which the G13D mutation induced the effects, we studied both RAS/ERK and PI3K/Akt pathways using specific inhibitors SCH772984 and BEZ235. The results indicated that RAS/ERK rather than PI3K/Akt pathway was involved. As CSCs play the initial role in cancer development and the inflammation is a vital step during tumor initiation, we analyzed the correlation between increased stemness and inflammation. We found a close correlation of increased Lgr5 and CD133 with proinflammatory factors like IL-17, IL-22, and IL-23. Together, our findings suggest that K-RasG13D mutation promotes cancer cell growth but decreases cancer stemness and inflammation thus tumorigenesis and metastasis potential in colon cancer. Inhibition of this mutation reverses the process. Therefore, care needs be taken when employing targeted therapies to K-RasG13D mutations in clinics.

ObjectiveExcessive carbohydrate intake is a high risk factor for increased morbidity of type 2 diabetes (T2D). A novel regimen for the dietary care of diabetes that consists of a highly active α-amylase inhibitor derived from white common bean extract (WCBE) and sufficient carbohydrates intake was applied to attenuate T2D and its complications. Furthermore, the role of gut microbiota in this remission was also investigated.MethodsWe conducted a 4-month randomized double-blinded placebo-controlled trial. During the intense intervention period, ninety subjects were randomly assigned to the control group (Group C) and WCBE group (Group W). Subjects in Group C were supplemented with 1.5 g of maltodextrin as a placebo. Subjects in Group W took 1.5 g of WCBE half an hour before a meal. Fifty-five participants continued the maintenance intervention receiving the previous dietary intervention whereas less frequent follow-up. The variation in biochemical, vasculopathy and neuropathy indicators and the structure of the fecal microbiota during the intervention was analyzed.ResultGlucose metabolism and diabetic complications showed superior remission in Group W with a 0.721 ± 0.742% decline of glycosylated hemoglobin after 4 months. The proportion of patients with diabetic peripheral neuropathy (Toronto Clinical Scoring System, TCSS ≥ 6) was significantly lower in Group W than in Group C. Both the left and right sural sensory nerve conduction velocity (SNCV-left sural and SNCV-right sural) slightly decreased in Group C and slightly increased in Group W. Additionally, the abundances of Bifidobacterium, Faecalibacterium and Anaerostipes were higher in Group W, and the abundances of Weissella, Klebsiella, Cronobacter and Enterobacteriaceae_unclassified were lower than those in Group C at month 2. At the end of month 4, Bifidobacterium remained more abundant in Group W.ConclusionTo our knowledge, this is the first report of improvement to diabetes complications by using a dietary supplement in such a short-term period. The enrichment of SCFA-producing bacteria might be responsible for the attenuation of T2D and its complications.Clinical trial registration numberhttp://www.chictr.org.cn/edit.aspx?pid=23309&htm=4, identifier ChiCTR-IOR-17013656

Nutritional disorders have become a major public health issue, requiring increased targeted approaches. Personalized nutrition adapted to individual needs has garnered dramatic attention as an effective way to improve nutritional balance and maintain health. With the rapidly evolving fields of genomics and nutrigenetics, accumulation of genetic variants has been indicated to alter the effects of nutritional supplementation, suggesting its indispensable role in the genotype-based personalized nutrition. Additionally, the metabolism of nutrients, such as lipids, especially omega-3 polyunsaturated fatty acids, glucose, vitamin A, folic acid, vitamin D, iron, and calcium could be effectively improved with related genetic variants. This review focuses on existing literatures linking critical genetic variants to the nutrient and the ways in which these variants influence the outcomes of certain nutritional supplementations. Although further studies are required in this direction, such evidence provides valuable insights for the guidance of appropriate interventions using genetic information, thus paving the way for the smooth transition of conventional generic approach to genotype-based personalized nutrition.

Abstract Background Dermatofibrosarcoma protuberans (DFSP) is a rare, low- to intermediate-grade sarcoma, which represents a diagnostic imaging challenge. This study aimed to analyze the clinical and ultrasound features of primary and recurrent DFSP to improve the diagnosis. Methods Clinical, imaging, and pathological data from a total of 58 patients (23 patients with primary DFSP and 35 patients with recurrent DFSP) were retrospectively reviewed. Results There was no statistically significant difference in age, sex, tumor size, or echogenicity between the two groups. Most of the primary DFSP lesions involved the overlying dermis and hypodermis, while most of the recurrent DFSP lesions were fixated to more deeply seated structures at the original surgical incision. Red nodules on the skin were found more frequently in the primary group. There were statistically significant differences in the type of lesion and ultrasound tumor morphology (p

Energetic electron measurements and spacecraft charging are of great significance for theoretical research in space physics and space weather applications. In this paper, the energetic electron detection package (EEDP) deployed on three Chinese navigation satellites in medium Earth orbit (MEO) is reviewed. The instrument was developed by the space science payload team led by Peking University. The EEDP includes a pinhole medium-energy electron spectrometer (MES), a high-energy electron detector (HED) based on ΔE-E telescope technology, and a deep dielectric charging monitor (DDCM). The MES measures the energy spectra of 50−600 keV electrons from nine directions with a 180°×30° field of view (FOV). The HED measures the energy spectrum of 0.5−3.0 MeV electrons from one direction with a 30° cone-angle FOV. The ground test and calibration results indicate that these three sensors exhibit excellent performance. Preliminary observations show that the electron spectra measured by the MES and HED are in good agreement with the results from the magnetic electron-ion spectrometer (MagEIS) of the Van Allen Probes spacecraft, with an average relative deviation of 27.3% for the energy spectra. The charging currents and voltages measured by the DDCM during storms are consistent with the high-energy electron observations of the HED, demonstrating the effectiveness of the DDCM. The observations of the EEDP on board the three MEO satellites can provide important support for theoretical research on the radiation belts and the applications related to space weather.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a significant global human health threat. The most effective way to end the pandemic is through timely vaccination. In this study, the receptor-binding domains (RBDs) of Spike protein of the initial strain of SARS-CoV-2 and its variants, B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.1 (Kappa), were successfully displayed on the surface of a Saccharomyces cerevisiae strain for development as a vaccine candidate. To rapidly express the recombinant protein and avoid the need for expensive galactose as an inducer, the gal80 gene of S. cerevisiae was knocked out, and the conventional 72-h culture period was thus successfully shortened to 24 h. Mice vaccinated against variant B.1.617.1 showed robust humoral and cellular immune responses. Moreover, the antiserum in the B.1.671.1 group had neutralizing activity against wild-type RBD and high binding titers against RBD mutants of variants B.1.351 and B.1.1.7. Double deglycosylation at N331Q and N343Q resulted in marked reduction of the affinity of RBD binding to angiotensin converting enzyme 2 (ACE2) and escaped antibody neutralization. This study demonstrates that yeast surface display technology can provide an alternative approach to rapid large-scale preparation of promising SARS-CoV-2 vaccine candidates at low cost.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer mortality globally. Large bowel obstruction (occurring in 15-30% of patients with CRCs) accounts for approximately 80% of medical emergencies related to CRC. Currently, there is no standard treatment of this condition. The European Society of Gastrointestinal Endoscopy (ESGE) recommends self-expandable metal stent (SEMS) as a bridge (two weeks) to surgery for left-sided obstructing colon cancer. In the present report, we describe an 81-year-old male with colon cancer who underwent colon stent placement for 32 months, but later underwent radical resection. A follow-up of more than four-months revealed that his condition was normal. The history as well as application and advantages of SEMS are discussed in this report.

ObjectivesThis systematic review and meta-analysis was conducted to identify the potential risk factors for postoperative delirium in geriatric patients with hip fracture.MethodsPubMed, EMBASE, and Cochrane Library were searched from inception until December 31st, 2021. A combined searching strategy of subject words and free words was adopted. Studies involving risk factors for postoperative delirium in elderly patients undergoing hip fracture surgeries were reviewed. Qualities of included studies were assessed using the Newcastle–Ottawa Scale. Data were pooled and a meta-analysis was performed using Review Manager 5.3.ResultsA total of 37 studies were included. The following risk factors were significant: advanced age (per year increase) (OR: 1.05, 95% CI 1.04–1.07), age>80 years (OR: 2.26, 95% CI 1.47–3.47), male (OR: 1.53, 95% CI 1.37–1.70), preoperative cognitive impairment (OR:3.20, 95% CI 2.12–4.83), preoperative dementia (OR: 2.74, 95% CI 2.18–3.45), preoperative delirium (OR: 9.23, 95% CI 8.26–10.32), diabetes (OR: 1.18, 95% CI 1.05–1.33), preoperative functional dependence (OR: 1.31, 95% CI 1.11–1.56), ASA level (per level increase) (OR: 1.63, 95% CI 1.04–2.57), ASA level≥3(OR: 1.76, 95% CI 1.39–2.24), low albumin (OR: 3.30, 95% CI 1.44–7.55), medical comorbidities (OR: 1.15, 95% CI 1.06–1.25), Parkinson's disease (OR: 4.17, 95% CI 1.68–10.31) and surgery delay>48 h (OR: 1.90, 95% CI 1.36–2.65).ConclusionsClinicians should be alert to patients with those risk factors. To identify the risk factors more precisely, more research studies with larger sample size and better design should be conducted.

Profiles of the Martian dayside ionosphere can be used to derive the neutral atmospheric densities at 130 km, which can also be obtained from the Mars Climate Database (MCD) and spacecraft aerobraking observations. In this research, we explain the method used to calculate neutral densities at 130 km via ionosphere observations and three long-period 130-km neutral density data sets at northern high latitudes (latitudes > 60°) acquired through ionospheric data measured by the Mars Global Surveyor (MGS) Radio Occultation Experiment. The calculated 130-km neutral density data, along with 130-km density data from the aerobraking observations of the MGS and Mars Odyssey (ODY) in the northern high latitudes, were compared with MCD outputs at the same latitude, longitude, altitude, solar latitude, and local time. The 130-km density data derived from both the ionospheric profiles and aerobraking observations were found to show seasonal variations similar to those in the MCD data. With a negative shift of about 2 × 1010 cm−3, the corrected 130-km neutral densities derived from MCD v4.3 were consistent with those obtained from the two different observations. This result means that (1) the method used to derive the 130-km neutral densities with ionospheric profiles was effective, (2) the MCD v4.3 data sets generally overestimated the 130-km neutral densities at high latitudes, and (3) the neutral density observations from the MGS Radio Science Experiment could be used to calibrate a new atmospheric model of Mars.

Abstract Luminescent metal–organic frameworks (MOFs) are appealing for the design of smart responsive materials, whereas aggregation‐induced emission (AIE) fluorophores with twisted molecular rotor structure provide exciting opportunities to construct MOFs with new topology and responsiveness. Herein, it is reported that elongating AIE rotor ligands can render the newly formed AIE MOF (ZnETTB) (ETTB = 4',4''',4''''',4'''''''‐(ethene‐1,1,2,2‐tetrayl)tetrakis(([1,1'‐biphenyl]‐3,5‐dicarboxylic acid))) with more elasticity, more control for intramolecular motion, and specific amide‐sensing capability. ZnETTB shows specific host–guest interaction with amide, where N,N‐diethylformamide (DEF), as an example, is anchored through CH···O and CH···π bonds with Zn cluster and ETTB8− ligand, respectively. DEF anchoring reduces both the distortion level and the intramolecular motions of ETTB8− ligand to lead a blueshifted and intensified emission for DEF ∈ ZnETTB. Moreover, amide anchoring also affords the DEF ∈ ZnETTB with the excellent thermofluorochromic behavior, and further increases the piezofluorochromic sensitivity at low‐pressure ranges on the basis of its elastic framework. This work is one of the rare examples of amide‐responsive smart materials, which shall shed new lights on design of smart MOFs with twisted AIE rotors for further sensing and detection applications.

In contrast to highly conserved mitogenomic architecture in most metazoan lineages, which indicates that rearrangement events are generally strongly selected against, a limited number of often unrelated lineages exhibit highly elevated architectural evolution rates. The underlying reasons for this discontinuity in the mitogenomic evolution remain unknown. Previously we sequenced the mitochondrial genome of the first Camallanoidea species, Camallanus cotti (Nematoda: Chromadorea: Spirurina: Camallanidae), and found that it exhibited a highly disrupted architecture. We hypothesised that disrupted architecture might be a synapomorphic feature of the sister-clades Camallanoidea and Dracunculoidea. In this study, we sequenced mitogenomes of three freshwater fish-parasitic nematodes: Camallanus lacustris (Camallanidae), and two Philometridae (Dracunculoidea) species, Clavinema parasiluri, and Philometra sp. In partial agreement with the working hypothesis, both Camallanoidea species had exceptionally large mitogenomes of 18–19 Kbp, albeit the underlying reasons differed: in C. lacustris it was the existence of a single enlarged noncoding region of ≈5.5 Kbp. A segment of this region exhibited an inverted base composition skew, which is indicative of a sequence inversion or recombination event. Camallanidae is the second identified chromadorean (first for Spirurina) family that exhibits within-family protein-coding gene rearrangements, and the absence of trnL1 and trnF may be a synapomorphy for Camallanoidea. The underlying reason for the disrupted architecture of Camallanidae does not appear to be a particular event shared by their common ancestor, but rather an underlying mechanism that makes disruptive events more likely in this lineage. In disagreement with the working hypothesis, Spiruromorpha and Oxyuridomorpha exhibited even more highly rearranged gene orders and greater overall branch lengths than Camallanomorpha. However, within-infraorder architecture was highly conserved and leaf nodes very short. This indicates that common ancestors of Spiruromorpha and Oxyuridomorpha clades underwent a period of rapid mitochondrial evolution (both sequence and architecture), followed by a stabilisation after the taxonomic radiation. In contrast to this, Camallanomorpha, and particularly Camallanidae, appear to have entered a period of elevated evolutionary rates after the initial radiations of these two taxa. As a result of this evolutionary discontinuity, there was a strong correlation between the gene order rearrangement rate (GORR) and the overall branch length (0.81), but there was no correlation between the strength of purifying selection (ω ​= ​dN/dS) and the overall branch lengths (−0.05) and GORR (−0.04). These findings have important repercussions for future phylogenetic and other evolutionary studies of Spirurina.

Gut microbiota plays an important role in metabolic homeostasis. Previous studies demonstrated that ginsenoside Rb1 might improve obesity-induced metabolic disorders through regulating glucose and lipid metabolism in the liver and adipose tissues. Due to low bioavailability and enrichment in the intestinal tract of Rb1, we hypothesized that modulation of the gut microbiota might account for its pharmacological effects as well. Here, we show that oral administration of Rb1 significantly decreased serum LDL-c, TG, insulin, and insulin resistance index (HOMA-IR) in mice with a high-fat diet (HFD). Dynamic profiling of the gut microbiota showed that this metabolic improvement was accompanied by restoring of relative abundance of some key bacterial genera. In addition, the free fatty acids profiles in feces were significantly different between the HFD-fed mice with or without Rb1. The content of eight long-chain fatty acids (LCFAs) was significantly increased in mice with Rb1, which was positively correlated with the increase of Akkermansia and Parasuttereller, and negatively correlated with the decrease of Oscillibacter and Intestinimonas. Among these eight increased LCFAs, eicosapentaenoic acid (EPA), octadecenoic acids, and myristic acid were positively correlated with metabolic improvement. Furthermore, the colonic expression of the free fatty acid receptors 4 (Ffar4) gene was significantly upregulated after Rb1 treatment, in response to a notable increase of LCFA in feces. These findings suggested that Rb1 likely modulated the gut microbiota and intestinal free fatty acids profiles, which should be beneficial for the improvement of metabolic disorders in HFD-fed mice. This study provides a novel mechanism of Rb1 for the treatment of metabolic disorders induced by obesity, which may provide a therapeutic avenue for the development of new nutraceutical-based remedies for treating metabolic diseases, such as hyperlipidemia, insulin resistance, and type 2 diabetes.

Fractures have an extraordinarily negative impact on an individual’s quality of life and functional status, particularly delayed or non-union fractures. Osteogenesis and angiogenesis are closely related to bone growth and regeneration, and bone modeling and remodeling. Recently Chinese medicine has been extensively studied to promote osteogenic differentiation in MSCs. Studies have found that Ginseng can be used as an alternative for tissue regeneration and engineering. Ginseng is a commonly used herbal medicine in clinical practice, and one of its components, Ginsenoside Compound K (CK), has received much attention. Evidence indicates that CK has health-promoting effects in inflammation, atherosclerosis, diabetics, aging, etc. But relatively little is known about its effect on bone regeneration and the underlying cellular and molecular mechanisms. In this study, CK was found to promote osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) by RT-PCR and Alizarin Red S staining in vitro. Mechanistically, we found CK could promote osteogenesis through activating Wnt/β-catenin signaling pathway by immunofluorescence staining and luciferase reporter assay. And we also showed that the tube formation capacity of human umbilical vein endothelial cells (HUVECs) was increased by CK. Furthermore, using the rat open femoral fracture model, we found that CK could improve fracture repair as demonstrated by Micro-CT, biomechanical and histology staining analysis. The formation of H type vessel in the fracture callus was also increased by CK. These findings provide a scientific basis for treating fractures with CK, which may expand its application in clinical practice.

We describe the characterization of a novel fish leech species found on the gills of bighead carp (Hypophthalmichthys nobilis) from lakes and reservoirs in China. This leech is morphologically similar to Limnotrachelobdella sinensis recorded on goldfish and common carp. However, there are 0–2 pairs of symmetrical or asymmetrical eyes and 10 pairs of pulsatile vesicles in the newly discovered leech, in remarkable contrast to L. sinensis. Except for bighead carp, where it demonstrated a higher than 90% prevalence, and silver carp (H. molitrix), where there was low infection, this leech was not detected on any other fish from the Qiandao reservoir in China that were examined during this investigation. Molecular analyses indicated 87.8% ITS sequence identity with L. sinensis and 85.0 and 86.1% COX1 sequence identity with L. sinensis and L. okae, respectively. The uncorrected p-distance based on the COX1 sequence was found to be 15.1 and 14.0% for L. sinensis and L. okae, respectively, suggesting interspecific variation. Phylogenetic analyses based on the combination of 18S and COX1 sequences showed that the newly discovered leech groups with Limnotrachelobdella species. Histopathological observation indicated that attachment of the leech on the gill rakers and gill arches causes a loss of connective tissue, hemorrhage, and ulceration. Based on the morphology, molecular analyses, and host specificity, we conclude that this leech is a new species of Limnotrachelobdella and named it Limnotrachelobdella hypophthalmichthysa n. sp.

Alfven-branch waves provide an efficient means for transporting energy into the auroral oval. Here, we report observations of these waves obtained by the Fengyun-3E (FY-3E)/ACMag instruments, which are designed to detect three-dimensional AC magnetic fields in the 0.05–25 Hz band. The observations suggest that broadband waves are a permanent feature of the auroral oval, although their amplitude and locations vary with the global state of the magnetosphere. We primarily focus on the data obtained from 10 July 2021 to 26 August 2021, during which a series of recurrent storms driven by solar wind corotating interaction regions (CIRs) occurred. Analysis of the observations shows that the auroral-oval waves grow in amplitude (1–3 orders of magnitude) and shift to lower latitude (∼10°) immediately following the decrease in the SYM-H index in each storm. Further investigation reveals the response of the auroral-oval waves has a time scale equal to or less than FY-3E’s effective revisiting time, which is about 45 min. The observations presented in this paper confirm that the FY-3E/ACMag instruments provide a high-resolution monitor of the auroral-oval waves and could further our understanding of auroral physics.

Immunotherapy has developed rapidly and has gradually become one of the important methods for treatment of gastric cancer (GC). The research on tumor infiltrating immune cells (TIICs) and immune-related genes in the tumor microenvironment (TME) greatly encourages the development of immunotherapy. The devolution algorithm (CIBERSORT) was applied to infer the proportion of 22 TIICs based on gene expression profiles of GC tissues, which were downloaded from TCGA and GEO. TCGA was utilized to analyze the differential expression of immune-related genes, and explore the potential molecular functions of these genes. We have observed the enrichment of multiple TIICs in microenvironment of GC. Some of these cells were closely related to tumor mutational burden (TMB), microsatellite instability (MSI), Fuhrman grade, and TNM staging. Survival analysis showed that the infiltration level of CD8+ T cells, activated CD4+ memory T cells and M2 macrophages were significantly related to the prognosis of GC patients. The functional enrichment analysis of immune-related genes revealed that these genes were mainly associated with cytokine activation and response. Four significant modules were screened by PPI network and 20 key genes were screened from the modules. The expression levels of CALCR and PTH1R are strikingly related to the expression of immune checkpoint and the prognosis of GC patients. The type and number of TIICs in microenvironment of GC, as well as immune-related genes are closely related to tumor progression, and can be used as important indicators for patient prognosis assessment.

In mammals, bile acid (BA) concentrations are regulated largely by the gut microbiota, and a study has shown that some metabolic responses to the gut microbiota are conserved between zebrafish and mice. However, it remains unknown whether the influence of specific intestinal microbes on BA metabolism is conserved between higher and lower vertebrates (i.e., mammals and fish). In the present study, Citrobacter freundii GC01 isolated from the grass carp (Ctenopharyngodon idella) intestine was supplemented to the fish and mice feed. We found the changes in the bile acid profile, especially significant changes in secondary BAs in both grass carp and mice fed on C. freundii. Also, lipid metabolism was significantly affected by C. freundii. Analysis of liver transcriptome sequencing data and validation by RT-qPCR revealed that the CYP7A1 gene was significantly up-regulated in both grass carp and mice. In addition, the overexpression of HNF4B from grass carp resulted in a significant increase in the expression level of CYP7A1. Generally, our results suggest that the metabolism of BAs by intestinal microbiota is conserved across vertebrates. Furthermore, specific intestinal bacteria may regulate the bile salt synthesis through CYP7A1 and that HNF4B might be an important regulator of BA metabolism in fish.

Our understanding of interactions among intestinal helminths, gut microbiota and host is still in its infancy in fish. In this study, the effects of Schyzocotyle acheilognathi infection on the intestinal microbiota, growth and immune reactions of grass carp were explored under laboratory conditions. 16S rDNA amplification sequencing results showed that S. acheilognathi infection altered the composition of intestinal microbiota only at the genus level, with a significant increase in the relative abundance of Turicibacter and Ruminococcus (P < 0.05) and a significant decrease in the relative abundance of Gordonia, Mycobacterium and Pseudocanthomonas (P < 0.05). Schyzocotyle acheilognathi infection had no significant effect (P > 0.05) on the alpha diversity indices (including Chao1, ACE, Shannon, Simpson index) of intestinal microbiota in grass carp, but PERMANOVA analysis showed that microbial structure significantly (P < 0.01) differed between hindgut and foregut. PICRUST prediction showed that some metabolism-related pathways were significantly changed after S. acheilognathi infection. The relative abundance of Turicibacter was positively correlated with the fresh weight of tapeworm (foregut: r = 0.48, P = 0.044; hindgut: r = 0.63, P = 0.005). There was no significant difference in the body condition of grass carp between the S. acheilognathi infected group and the uninfected group (P > 0.05). Intestinal tissue section with HE staining showed that S. acheilognathi infection severely damaged the intestinal villi, causing serious degeneration, necrosis and shedding of intestinal epithelial cells. The real-time fluorescent quantitative PCR results showed that S. acheilognathi infection upregulated the mRNA expression of the immune-related genes: Gal1−L2, TGF−β1 and IgM.

The rare minnow Gobiocypris rarus is an ideal model organism for toxicological research. Dactylogyrus species are usually found on the gills of this rare minnow in laboratory farming systems. Dactylogyrid infection may change the sensibility of fish to toxicants and affect toxicological evaluations. In the present study, dactylogyrid infection was investigated, and species of Dactylogyrus collected from rare minnows were determined. Based on the observed ‘D. wunderi’ type anchors, with a shorter outer root and elongated inner root, and accessory piece consisting of two parts, the dactylogyrids were identified as D. gobiocypris. A partial 18S-ITS1 rDNA sequence was firstly sequenced, and the highest sequence identity (86.7%) was to D. cryptomeres. Phylogenetic analysis revealed that D. gobiocypris formed a clade with D. squameus, D. finitimus, and D. cryptomeres, all of which have been recorded in the family Gobionidae. Histopathology analysis indicated that a heavy burden of D. gobiocypris caused necrosis of gill filaments. Inflammatory responses, such as tumefaction and hyperaemia, were also observed on gills with severe dactylogyrid infection. Supplementary morphological characteristics and 18S-ITS1 rDNA sequence provided basic data for identification of this parasite species.

Abstract Background Hepatocellular carcinoma (HCC) is the most common type of liver tumour, and is closely related to liver cirrhosis. Previous studies have focussed on the pathogenesis of liver cirrhosis developing into HCC, but the molecular mechanism remains unclear. The aims of the present study were to identify key genes related to the transformation of cirrhosis into HCC, and explore the associated molecular mechanisms. Methods GSE89377, GSE17548, GSE63898 and GSE54236 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analysed to obtain differentially expressed genes (DEGs) between HCC and liver cirrhosis tissues, and network analysis of protein–protein interactions (PPIs) was carried out. String and Cytoscape were used to analyse modules and identify hub genes, Kaplan–Meier Plotter and Oncomine databases were used to explore relationships between hub genes and disease occurrence, development and prognosis of HCC, and the molecular mechanism of the main hub gene was probed using Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Results In total, 58 DEGs were obtained, of which 12 and 46 were up- and down-regulated, respectively. Three hub genes (CDKN3, CYP2C9 and LCAT) were identified and associated prognostic information was obtained. CDKN3 may be correlated with the occurrence, invasion, and recurrence of HCC. Genes closely related to changes in the CDKN3 hub gene were screened, and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway analysis identified numerous cell cycle-related genes. Conclusion CDKN3 may affect the transformation of liver cirrhosis into HCC, and represents a new candidate molecular marker of the occurrence and progression of HCC.

Abstract Background Species belonging to the genus Lernaea are cosmopolitan parasites that can infect many different freshwater fish hosts. Due to a high degree of morphological intraspecific variability and high levels of interspecific similarities, their classification is extremely difficult and controversial. Although the suitability of the shape of cephalic horns has been questioned decades ago by some experimental infection studies, this character still plays the central role in the identification of Lernaea spp. Methods We used the nominal species Lernaea cyprinacea and Lernaea cruciata to test the hypothesis that the shape of the anchor can exhibit host-induced morphological variability, and that the two taxa may be synonymous. Results We examined 517 wild or farmed specimens of five host fish species (four cyprinids and a mosquitofish), and found that all 16 parasite specimens collected from mosquitofish could be morphologically identified as L. cruciata, whereas the remaining 25 parasite specimens were all identified as L. cyprinacea. We experimentally infected goldfish and mosquitofish specimens with offspring (copepodids) of a single L. cyprinacea specimen: the adult parasites from goldfish were morphologically identified as L. cyprinacea, and those from mosquitofish as L. cruciata. We then used molecular data to corroborate that all these specimens are conspecific. Conclusions Our results suggest that L. cyprinacea and L. cruciata may be synonyms, misidentified as different species as a result of host-induced morphological variation. Given the current shortage of molecular data for the genus Lernaea, in order to resolve the taxonomy of this genus (determine the exact number of species), future studies should aim to sequence as much molecular data as possible, and conduct further experimental infections.

Abstract Background Neuropsychiatric systemic lupus erythaematosus (NP-SLE) is one of the major manifestations of lupus. However, the mechanisms involved in NP-SLE are still largely unknown. The abnormal activation of the type I IFN signalling pathway is involved in SLE pathogenesis and is linked to NP-SLE, but the effect of IFN-α on NP-SLE encephalopathy has not been systematically studied. Methods An intravenous injection of Adv-IFN-α (10 mice, 10 × 109 vp) was administered to the IFN-α-treated group, and Adv-ctrl (10 mice, 10 × 109 vp) (ViGene Biosciences, China) was administered to the control group. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in the serum, and urinary protein levels were measured with a BCA Protein Assay kit. Haematoxylin-eosin (H&E) and periodic acid-Schiff (PAS)-light green staining were used for kidney histology. The elevated plus-maze test, novelty-suppressed feeding assay, open-field test, tail suspension test, social dominance tube test, three-chamber social interaction test, step-down passive avoidance test and novelty Y-maze task were used to assess behaviour. Results In this study, we performed a series of behavioural tests to assess the neuropsychiatric phenotypes of IFN-α-treated NZB/NZW F1 mice and found that these mice developed a series of mental disorders such as anxiety-like phenotypes, depression-like phenotypes, deficits in sociability and cognitive impairments, which mimic the neuropsychiatric manifestations of NP-SLE, with a consistent onset and progression. Conclusions Our research verified that IFN-α plays a critical role in NP-SLE and provides a comprehensive NP-SLE mouse model for dissecting the mechanisms of NP-SLE and developing novel therapies for intervention.

Abstract Mitogen-activated protein kinase kinase kinase 3 (MAP3K3), a member of the serine/threonine protein kinase family, is ubiquitously expressed and acts as an oncogene. However, the expression and exact molecular mechanism of MAP3K3 in ovarian carcinoma (OC) remain unclear. Here, we found that MAP3K3 protein was highly expressed in 70.5% of high-grade serous ovarian carcinoma (HGSOC) samples. MAP3K3 overexpression was significantly associated with the FIGO stage and chemotherapy response. Additionally, MAP3K3 overexpression was associated with reduced disease-free survival and overall survival. In vitro experiments showed that MAP3K3 overexpression promoted cell proliferation, inhibited apoptosis, and enhanced the migration and invasion of OC cells. Moreover, in vivo tumourigenesis experiments confirmed that silencing MAP3K3 significantly reduced the growth rate and volume of transplanted tumours in nude mice. Drug sensitivity experiments demonstrated that differential expression of MAP3K3 in OC cell lines correlates with chemotherapy resistance. Functionally, the MAP3K3 gene regulated the malignant biological behaviour of OC cells by mediating NF-κB signalling pathways, affecting the downstream epithelial-mesenchymal transition and cytoskeletal protein expression. Our results unveiled the role of MAP3K3 in mediating NF-κB signalling to promote the proliferation, invasion, migration, and chemotherapeutic resistance of OC cells, highlighting a potential new therapeutic and prognostic target.

Abstract Background Parasitic protozoans, helminths, alter the gut microbiota in mammals, yet little is known about the influence of intestinal cestodes on gut microbiota in fish. In the present study, the composition and diversity of the hindgut microbiota were determined in the intestine of common carp (Cyprinus carpio) infected with two tapeworm species, Khawia japonensis and Atractolytocestus tenuicollis. Results The intestine contained a core microbiota composed of Proteobacteria, Fusobacteria and Tenericutes. Infection with the two cestode species had no significant effect on the microbial diversity and richness, but it altered the microbial composition at the genus level. PCoA analysis indicated that microbial communities in the infected and uninfected common carp could not be distinguished from each other. However, a Mantel test indicated that the abundance of K. japonensis was significantly correlated with the microbial composition (P = 0.015), while the abundance of A. tenuicollis was not (P = 0.954). According to Pearsonʼs correlation analysis, the abundance of K. japonensis exhibited an extremely significant (P

Abstract Although dynamics of the complex microbial ecosystem populating the gastrointestinal tract of animals has profound and multifaceted impacts on host’s metabolism and health, it remains unclear whether it is the intrinsic or extrinsic factors that play a more dominant role in mediating the composition of intestinal microbiota. To address this, we studied the impacts of two strikingly different diets on a herbivorous fish, grass carp (Ctenopharyngodon idellus): a high-protein, low-fiber formula feed, and low-protein, high-fiber Sudan grass. After a 16-week feeding trial, microbial profiles of midgut and hindgut segments in both groups were compared. Bacterial composition was significantly different between the midguts of both groups, but not between the hindguts of two groups. Both PerMANOVA and VPA analyses suggested that gut segments explain a higher proportion of variation in intestinal microbiota than diet. Overall, our results suggest that intestinal compartments are a stronger determinant than diet in shaping the intestinal microbiota. Specifically, whereas diet has a strong impact on the composition of microbiota in proximal gut compartments, this impact is much less pronounced distally, which is likely to be a reflection of a limited ability of some microbial taxa to thrive in the anoxic environment in distal segments.

AIM:To analyze the differences of retinal thickness, retinal volume and choroidal thickness in the macular area in healthy people and patients with liver cirrhosis, and to explore the morphologic changes of retina and choroid in liver cirrhosis.METHODS: A cross-sectional study. From January 2015 to March 2018, 168 eyes of 84 patients with liver cirrhosis and 100 eyes of 50 healthy people were included. Healthy people were the normal control group. The patients were divided into two groups, including compensated cirrhosis group(68 eyes of 34 patients)and decompensated cirrhosis group(100 eyes of 50 patients). All eyes underwent OCT examination to measure the retinal thickness and retinal volume in the macular area. EDI-OCT was used for choroidal thickness scanning, and the vertical distance between the strong reflection of Bruch film and the strong reflection of the choroidal sclera interface was defined as the choroidal thickness. The retinal thickness, retinal volume and choroidal thickness in the macular area in the three groups were compared and analyzed.RESULTS: The differences in retinal thickness and retinal volume between three groups were not significant(P>0.05). The subfoveal choridal thickness(SFCT)of three groups were 338.50±70.44, 357.00±89.16, 319.53±74.37μm(P>0.05). There was a statistically significant difference in nasal choroid thickness between the three groups(PPCONCLUSION: The choridal thickness in nasal area to fovea in the patients with decompensated cirrhosis is thicker than that in healthy people. There are no significant differences in retinal thickness or retinal volume in macular area between healthy people and patients with liver cirrhosis.