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Abstract Peritoneal metastasis (PM), the regional progression of intra-abdominal malignancies, is a common sequelae of colorectal cancer (CRC). Immunotherapy is slated to be effective in generating long-lasting anti-tumour response as it utilizes the specificity and memory of the immune system. In the tumour microenvironment, tumour associated macrophages (TAMs) are posited to create an anti-inflammatory pro-tumorigenic environment. In this paper, we aimed to identify immunomodulatory factors associated with colorectal PM (CPM). A publicly available colorectal single cell database (GSE183916) was analysed to identify possible immunological markers that are associated with the activation of macrophages in cancers. Immunohistochemical analysis for V-set and immunoglobin containing domain 4 (VSIG4) expression was performed on tumour microarrays (TMAs) of tumours of colorectal origin (n = 211). Expression of VSIG4 in cell-free ascites obtained from CPM patients (n = 39) was determined using enzyme-linked immunosorbent assay (ELISA). CD163-positive TAMs cluster expression was extracted from a publicly available single cell database and evaluated for the top 100 genes. From these macrophage-expressed genes, VSIG4, a membrane protein produced by the M2 macrophages, mediates the up-regulation of anti-inflammatory and down-regulation of pro-inflammatory macrophages, contributing to an overall anti-inflammatory state. CRC TMA IHC staining showed that low expression of VSIG4 in stromal tissues of primary CRC are associated with poor prognosis (p = 0.0226). CPM ascites also contained varying concentrations of VSIG4, which points to a possible role of VSIG4 in the ascites. The contribution of VSIG4 to CPM development can be further evaluated for its potential as an immunotherapeutic agent.

Background/Objectives: China English, distinct from Chinese English or Chinglish, is struggling to get legitimized as a variety of the English language, despite many its users globally. The current study investigated the moderating effect of learner autonomy on the relationship between learner's attitude and learner's perception and China English (CE) as a variety of the English language. Methods/Statistical analysis: A questionnaire-based research design and utilized Pearson correlation analysis to test the hypotheses and SPSS-20 to analyze the data. The sample size was 120 Chinese EFL students who had studied at least one English course. Findings: The findings revealed that learner autonomy is enhanced due to the use of CE in classroom. This positive phenomenon was also noticed in the correlation between learner's attitude and learner's perception resulting in a high acceptance of CE as a variety of the English language. Improvements/Applications: This finding will give a positive thrust to the legitimizing issue of China English as a member of World Englishers. It may also contribute to the critical debate that is ongoing to change CE's status from a foreign language to China's own language and its users as Native speakers. Future studies can explore teachers' attitude towards CE and its influence on L2 teaching in China.

Inflammasome is linked to many inflammatory diseases, including COVID-19 and autoimmune liver diseases. While severe COVID-19 was reported to exacerbate liver failure, we report a fatal acute-on-chronic liver failure (ACLF) in a stable primary biliary cholangitis-autoimmune hepatitis overlap syndrome patient triggered by a mild COVID-19 infection. Postmortem liver biopsy showed sparse SARS-CoV-2-infected macrophages with extensive ASC (apoptosis-associated speck-like protein containing a CARD) speck-positive hepatocytes, correlating with elevated circulating ASC specks and inflammatory cytokines, and depleted blood monocyte subsets, indicating widespread liver inflammasome activation. This first report of a fatal inflammatory cascade in an autoimmune liver disease triggered by a mild remote viral infection hopes to elucidate a less-described pathophysiology of ACLF that could prompt consideration of new diagnostic and therapeutic options.

Abstract To investigate the molecular mechanism of Yiwei Decoction (YWD) in preventing Premature ovarian insufficiency (POI)-related osteoporosis from the hypothalamic perspective , and to screen for the key active and acting molecules in YWD. Cyclophosphamide was used to create the POI rat model. Groups A, B, and C were established. The Model + YWD group was group A, the model control group was group B, and the normal control group was group C. ELISA was used to determine serum GnRH and FSH levels after gavage. The transcription levels of mRNAs in each group's hypothalamus tissues were examined using RNA-seq sequencing technology. The GSEA method was used to enrich pathways based on the gene expression levels of each group. The TCM–active ingredient–target–disease network map was created using differentially expressed mRNAs (DEmRNAs) and network pharmacology. The molecular docking method was employed to investigate the affinity of the active ingredient with key targets. GnRH and FSH levels in POI rats' serum were reduced by YWD. Between groups A and B, there were 638 DEmRNAs (P

Abstract Background and purpose Tuberculosis (TB) is the most fatal infectious disease worldwide. Approximately 24.6% of tuberculosis cases are extrapulmonary and predominantly affect the spine. It is difficult to diagnose spinal TB (STB). We aimed to evaluate the diagnostic performance of the Mycobacteria Growth Indicator Tube (MGIT)-960 culture, T-SPOT.TB, Xpert Mycobacterium tuberculosis complex (MTB)/resistance to rifampin (RIF), and Metagenomic Next-Generation Sequencing (mNGS) to detect STB. Methods We assessed 126 patients presumed to have STB using these four methods. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using clinical diagnosis as a reference. Results Of the patients, 41 were diagnosed with STB and 85 with non-STB. In the STB group, the sensitivity, specificity, PPV, and NPV of the MGIT-960 culture were 29.3% (12/41), 100% (85/85), 100% (12/12), and 74.6% (85/114), respectively. The sensitivity, specificity, PPV, and NPV of T-SPOT.TB were 92.7% (38/41), 82.4% (70/85), 58.5% (31/53), and 95.9% (70/73), respectively. The sensitivity, specificity, PPV, and NPV of the Xpert MTB/RIF assay were 53.7% (22/41), 100% (85/85), 100% (22/22), and 81.7% (85/104), respectively. The sensitivity, specificity, PPV, and NPV of mNGS were 39.0% (16/41), 98.8% (84/85), 94.1% (16/17), and 77.1% (84/109), respectively. The sensitivity, specificity, PPV, and NPV of mNGS + Xpert MTB/RIF were 73.2% (30/41), 100% (85/85), 96.8% (30/31), and 72.0% (85/118), respectively. The sensitivity, specificity, PPV, and NPV of the mNGS + T-spot assay were 97.6% (40/41), 100% (85/85), 67.9% (38/56), and 75.9% (85/113), respectively. Moreover, the sensitivity, specificity, PPV, and NPV of T-spot + Xpert MTB/RIF were 95.1% (39/41), 100% (85/85), 72.2% (39/54), and 81.0% (85/105), respectively. Conclusions T-SPOT.TB is the most effective method for diagnosing STB; however, Xpert MTB/RIF is more reliable and can detect RIF resistance. Clinicians can use mNGS to identify pathogens in patients with spinal infections; these pathogens appeared to be more meaningful in guiding the clinical management of patients in the non-STB group. The combination of Xpert MTB/RIF and mNGS can improve the early diagnosis rate and drug resistance detection, reduce the diagnostic cycle, and provide early targeted anti-TB treatment for patients with STB.

Abstract Background The development of thoracic surgical techniques has provided a new avenue for treating thoracic tuberculosis. Moreover, microscopic treatment of spinal tuberculosis has attracted increasing attention, as it affords good visual access and reduces trauma. Traditional thoracoscopic treatment of spinal tuberculosis usually requires 2–3 passages, accompanied by a corresponding number of incisions. With a large number of conventional thoracoscopic surgeries performed, improved resolution of the microscopic field of view, effective hemostasis of the peripheral vessels using the ultrasonic knife, and many reports in the literature, thoracic tuberculosis can now be treated microscopically by creating a single channel. The aim of this study was to explore the feasibility and surgical technique for thoracic tuberculous spondylitis treatment via debridement and bone graft fusion surgery employing pure uniportal video-assisted thoracic surgery (VATS), combined with posterior internal fixation. Methods Seven patients with relatively complete documentation were included in this study. All patients underwent lesion removal and bone graft reconstruction via uniportal VATS with posterior internal fixation. The mean patient age was 39.6 years. Surgical duration, blood loss volume, postoperative recovery time, and thoracic kyphosis angle were recorded. Results The surgeries were successful with no severe postoperative complications. All patients were followed-up, and no recurrence of tuberculosis was observed. Imaging data, including computed tomography scans, confirmed the complete removal of the lesions. Additionally, bone fusion at the graft site was successful, no loss of the thoracic kyphosis angle was noted postoperatively, and the thoracic kyphosis angle improved. Conclusions Pure uniportal VATS yields satisfactory results and inflicts less trauma than previous surgical techniques. This technique also offers a reference value for treating thoracic tuberculous spondylitis.

Background: The aging-induced decrease in intestinal barrier function contributes to many age-related diseases. Studies on preventive measures for “leaky gut” may help improve the quality of life of geriatric patients. The potent anti-aging effect of Gastrodia elata and parishin, which is one of its active ingredients, has been reported previously. However, their effects on the gut remain elusive, and the effect of parishin on mammals has not been studied. Methods: We used quantitative RT-PCR, western blotting, immunohistochemical analysis, and 16S rRNA sequencing to investigate the effect of G. elata and parishin on the intestinal barrier function of D-Gal-induced aging mice. Results: G. elata and parishin prevented the decrease in tight junction protein (TJP) expression and morphological changes, modulated the composition of fecal microbiota to a healthier state, and reversed the translocation of microbial toxins and systemic inflammation. The correlation analyses showed that TJP expression and systemic inflammation were significantly positively or negatively correlated with the composition of fecal microbiota after G. elata and parishin administration. Additionally, TJP expression was also correlated with systemic inflammation. Moreover, G. elata and parishin administration reversed the decreased or increased expression of aging-related biomarkers, such as FOXO3a, SIRT1, CASPASE3 and P21, in the gut. Conclusions: These results suggested that G. elata and parishin could prevent gut aging and ameliorate the “leaky gut” of aged mice and that the underlying mechanism is related to the mutual correlations among barrier function, fecal microbiota composition, and inflammation.

DNA methylation plays an important role in plant development and response to multiple environmental stresses that cause a DNA methylation variation and likely persist in the process of gene expressions. In this study, we report an effect of salt stress (SS) at a 9:1 ratio of NaCl to Na2SO4 as well as alkali stress (AS) at a 9:1 ratio of NaHCO3 to Na2CO3 in sunflower on the DNA methylation. The results showed the DNA methylation at CG locations in sunflower leaves was much higher than that in roots, but more variations of the DNA methylation occurred in roots under two stresses, especially the alkali one. In addition, qRT-PCR validations further revealed significant changes in the gene expression pertaining to the DNA methylations, especially in roots. We hypothesized that roots were the first plant parts to be in contact with various abiotic stresses from the surrounding soil, sent out the stress signals throughout the whole plant, and then make adaptive responses quickly. Our findings from this study have provided some evidence that DNA methylation might be directly involved the signal generation and transmission in roots, which modifies DNAs and regulates the signally more extensively and sophisticatedly in roots than those in leaves. The intensified mechanism and regulation of DNA methylation in sunflower roots are very much involved in plant alkali tolerance and deserve a further investigation thoroughly.

Inflammasome is linked to many inflammatory diseases, including COVID-19 and autoimmune liver diseases. While severe COVID-19 was reported to exacerbate liver failure, we report a fatal acute-on-chronic liver failure (ACLF) in a stable primary biliary cholangitis-autoimmune hepatitis overlap syndrome patient triggered by a mild COVID-19 infection. Postmortem liver biopsy showed sparse SARS-CoV-2-infected macrophages with extensive ASC (apoptosis-associated speck-like protein containing a CARD) speck-positive hepatocytes, correlating with elevated circulating ASC specks and inflammatory cytokines, and depleted blood monocyte subsets, indicating widespread liver inflammasome activation. This first report of a fatal inflammatory cascade in an autoimmune liver disease triggered by a mild remote viral infection hopes to elucidate a less-described pathophysiology of ACLF that could prompt consideration of new diagnostic and therapeutic options. [ABSTRACT FROM AUTHOR]

Ti-V-based alloys are proved of huge potential in storing hydrogen, but the incomplete reversible hydrogen storage capacity caused by overstability of V hydride has limited the large-scale application. In this study, Ti32V40+xFe23-xMn5 (x=0, 4, 8, 12, at.%) alloys were designed, and the effects of V/Fe ratio on phase constitution and hydrogen storage properties were investigated. The main phase of the alloys is body-centered cubic (BCC) phase, and the lattice constants of the BCC phase decrease with the decrease of V/Fe ratio. Moreover, C14 Laves phase exists in alloys with a Fe content of 19at.% to 23at.%. For hydrogenation, the C14 Laves phase can accelerate the hydrogen absorption rate, but the hydrogen absorption capacity is reduced. With the decrease of V/Fe ratio, the hydride gradually destabilizes. Owing to its large lattice constant and high hydrogen absorption phase content, the Ti32V52Fe11Mn5 alloy shows the most enhanced hydrogen storage properties with hydrogenation and dehydrogenation capacities of 3.588wt.% at 298 K and 1.688wt.% at 343 K, respectively. The hydrogen absorption capacity of this alloy can be reserved to 3.574wt.% after 20 cycles of hydrogen absorption and desorption. [ABSTRACT FROM AUTHOR]

At present, the drug treatment for invasive fungal infection is challenged by serious adverse effects and drug resistance. Therefore, the research and development of safe and effective new antifungal drugs is a great importance to support the clinical treatment of invasive fungal diseases. This article reviewed new targets of invasive fungi, and explores the underlying mechanisms of fungal biofilm formation, cell wall,key metabolic enzymes, mitochondria in the aspects of small molecule inhibitors and secondary metabolites, which may provide reference for the research and development of new drugs.

BackgroundAdding induction chemotherapy to concurrent platinum-based chemoradiotherapy has significantly prolonged the survival time of patients with locoregionally advanced nasopharyngeal carcinoma. In this study, we intend to evaluate the survival outcomes, responses, and incidences of toxicities of induction chemotherapy and the differences between different strategies.MethodsA comprehensive search was conducted in PubMed, Embase, Web of Science, and Cochrane CENTRAL on August 10, 2021. Single-arm or multi-arm prospective clinical trials on induction chemotherapy without targeted therapies or immune checkpoint inhibitors were included. Primary outcomes included survival outcomes, objective response rate, and disease control rate, and the secondary outcome was the rates of grade 3 or higher treatment-related adverse events.ResultsThe 39 studies included in the systematic review and meta-analysis comprised 36 clinical trials and 5389 patients. The estimates for 3-year overall and fail-free survival rates were 87% and 77%. The estimates for 5-year rates of overall and fail-free survival were 81% and 73%. Gemcitabine plus platinum and docetaxel combined with 5-fluorouracil plus platinum strategies were associated with the highest rates of 3-year and 5-year overall survival. The objective response and disease control rates were 85% and 98% after the completion of induction chemotherapy. Neutropenia (27%) and nausea/vomiting (7%) were the most common grade 3 or higher treatment-related hematological and non-hematological adverse events during the induction phase.ConclusionsDifferent induction chemotherapeutic strategies appear to have varying effects and risks; a comprehensive summary of the survival outcomes, responses, and toxicities in clinical trials may provide a crucial guide for clinicians.

Background: Some studies have researched the correlation between flipped learning and cognitive learning outcomes; however, there is a paucity of research elaborating on the effects of flipped language learning on cognitive load (CL). Objectives: This study investigates the effects of using flipped learning designs (student‐led, teacher‐led and collaboration‐led) on learning outcomes and CL management during out‐of‐class activities versus during‐class activities. Methods: A mixed methods research was used to concurrently triangulate different strands of data on the effects of flipped learning designs on English as foreign language (EFL) learners' learning outcomes and CL. A total of 122 EFL learners were randomly assigned to either the control or experimental group and participated in the study. The interpretations were made based on running one‐way analysis of variance between four groups. Results and Conclusion: This study evidenced the efficacy of the interactive use of collaboration‐led flipped learning design over student‐led and teacher‐led designs for improving learning outcomes and lowering CL during computer‐assisted language learning (CALL) course. Pedagogically, CALL practitioners need to develop and integrate a well‐organized combination of student‐led and teacher‐led flipped learning activities for during‐class and out‐of‐class phases with respect to the CL and learning material complexity, while also considering the specific contexts and goals of their instructional settings. Theoretically, the results indicate the necessity of merging active learning and sociocultural theories into an instructional design to take advantage of the identified affordances of flipped language learning approach in terms of psychological effects (CL management) and learning effects (CALL outcomes). Lay Description: What is already known about this topic: The flipped language learning approach involves receiving online instruction outside the classroom and is a learner‐centered pedagogy. What this paper adds: This study contributes by triangulating different strands of data on the effects of flipped learning designs on learning outcomes and cognitive load.The findings highlight the effectiveness of collaboration‐led design for flipped language learning, facilitating engagement in both out‐of‐class and during‐class activities. Implications for practice: The findings emphasize the importance of designing and implementing instructional designs that align with emerging educational technologies.Teachers should consider the flexibility, fluency and novelty of the learning material when designing flipped learning activities. [ABSTRACT FROM AUTHOR]

Objective To investigate the application value of acoustic radiation force impulse imaging in preoperative prediction for efficacy of High-Intensity Focused Ultrasound uterine fibroids ablation Methods A prospective study was conducted on 32 women (41 fibroids) undergoing HIFU uterine fibroids ablation between January 2019 and September 2019. The virtual touch tissue quantification (VTQ) technique was used for the preoperative determination of uterine fibroids shear wave velocity (SWV). The stiffness of the preoperative uterine fibroids was graded on a virtual touch tissue image (VTI). All uterine fibroids were ablated with a single point ablation acoustic power of 400 W. All patients underwent pelvic cavity MRI examination for the measurement of the size, volume and non-perfused volume (NPV) of fibroids within the first month after HIFU ablation. The ablation rate of uterine fibroids was calculated according to the formula: ablation rate = NPV × 100/target fibroid volume. The patients were divided into two groups based on the postoperative ablation rate: ≥70% ablation rate group, and＜70% ablation rate group. The preoperative SWV and VTI grade of uterine fibroids were compared between the two groups. The correlation of preoperative uterine fibroids’ SWV and VTI grade with HIFU ablation rate were analyzed using the Spearman’s correlation coefficient. The optimal cutoff points in preoperative uterine fibroids SWV of 70% ablation rate were determined by receiver operating curve (ROC) analysis. Results A total of 30 patients (73.17%, 30/41) showed ablation rate ≥70%, with preoperative uterine fibroids’ SWV values of (3.42 ± 0.71) m/s. Of these, 24 patients (80%, 24/30) had VTI grades II–III. On the other hand, 26.83% (11/41) showed ablation rate

Objective To explore correlations between the therapeutic effect of high intensity focused ultrasound (HIFU) and histopathological characteristics of uterine fibroids with different Shear Wave Velocity (SWV) values. Methods A retrospective study was conducted on 36 women (43 fibroids) who had undergone high intensity focused ultrasound (HIFU) uterine fibroids ablation between January 2019 and January 2020. Preoperative fibroids tissue sections were obtained for histopathological examination. The pathological sections were stained with Masson-trichrome, and were observed and imaged under a Low-power microscope (4 × 10), while the smooth muscle cell (SMC) and collagen fiber content were semi-quantitatively measured. Preoperative fibroid SWV was measured using the Virtual Touch tissue quantification (VTQ) technique. Within one month after HIFU ablation, all patients had undergone a pelvic cavity MRI examination, which measured the size, volume, and non-perfused volume (NPV) of the fibroids. The formula: the ablation rate = NPV/target fibroid volume × 100% was used to calculate the ablation rate of the uterine fibroids. Correlation analysis of SWV values, HIFU ablation rate, along with the smooth muscle cell (SMC) and collagen fiber content, were conducted using the Spearman’s correlation test. Results The collagen fiber and SMC content of the preoperative fibroids were 32.09 ± 15.90%/view and 37.61 ± 15.32%/view, respectively. Preoperative fibroid SWV value was 3.56 ± 0.71 m/s. Preoperative fibroid SWV was negatively correlated with SMC content (r = −0.445, p = 0.003), but positively correlated with collagen fiber content (r = 0.454, p = 0.002). The ablation rate was negatively correlated with collagen fiber content (r = −0.377, p = 0.013), but positively correlated with SMC content (r = 0.402, p = 0.007). Conclusion Differences in histopathological characteristics may be important factors that induce differences in the therapeutic effects of HIFU ablation on uterine fibroids with different SWV values.

AimsChaperonin-containing TCP1 subunit (CCT) 6A is an oncogenic 6th subunit of the CCT family. Nevertheless, not much is documented regarding its function in colorectal cancer (COAD). This investigation seeks to explore the role of CCT6A in the prognosis of COAD.Main MethodsSequencing data from the Gene Expression Omnibus (GEO) and Cancer Genome Atlas database (TCGA) were employed to analyze the expression of CCT6A and its involvement in various regulatory networks behind COAD. Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) analyzed Levels of expression and survival rates, while GEPIA was used to uncover further the functional networks that involved CCT6A. Database for Annotation, Visualization, and Integrated Discovery (DAVID) tools were used to interpret Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Evaluation of the expression levels of CCT6A in COAD samples was also verified via immunohistochemistry.Key FindingsWe found that the expression of CCT6A is up-regulated in COAD. CCT6A correlated with poor prognosis and decreased immune infiltrates such as CD4+ T cells, B cells, and dendritic cells. CCT6A is increased in COAD patients. CCT6A is associated with several gene networks related to the DDX family and mismatch repair pathways.SignificanceOur data showed that data mining was able to uncover data regarding levels of CCT6A and its involvement in genetic regulating pathways in COAD.

Recurrent pregnancy loss (RPL) is a disturbing disease in women, and 50% of RPL is reported to be associated with immune dysfunction. Most previous studies of RPL focused mainly on the relationship between RPL and either T cells or natural killer (NK) cells in peripheral blood and the decidua; few studies presented the systemic profiles of the peripheral immune cell subsets in RPL women. Herein, we simultaneously detected 63 immune cell phenotypes in the peripheral blood from nonpregnant women (NPW), women with a history of normal pregnancy (NP) and women with a history of RPL (RPL) by multi-parameter flow cytometry. The results demonstrated that the percentages of naïve CD4+ T cells, central memory CD4+ T cells, naïve CD8+ T cells, mature NK cells, Vδ1+ T cells and the ratio of Vδ1+ T cells/Vδ2+ T cells were significantly higher in the RPL group than those in the NPW and NP groups, whereas the percentages of terminal differentiated CD4+ T cells, effective memory CD4+ T cells, immature NK cells and Vδ2+ T cells were significantly lower in the RPL group than those in the NPW and NP groups. Interestingly, we found that peripheral T helper (TPH) cells were more abundant in the NPW group than in the NP and RPL groups. In addition, we also determined the 5th percentile lower limit and 95th percentile upper limit of the significantly changed immunological parameters based on the files of the NPW group. Taken together, this is the first study to simultaneously characterize the multiple immune cell subsets in the peripheral blood at a relatively large scale in RPL, which might provide a global readout of the immune status for clinicians to identify clinically-relevant immune disorders and guide them to make clear and individualized advice and treatment plans.

This article discusses the role of reactive oxygen species (ROS) and phosphatidic acid (PA) as important second messengers in plant immunity. The authors focus on the interaction between DGK5, a lipid kinase that regulates PA production, and RBOHD, an NADPH oxidase responsible for ROS production. They found that DGK5-derived PA stabilizes RBOHD, leading to enhanced ROS production and promoting plant immune responses. The authors also identified specific kinases that phosphorylate DGK5, regulating its enzymatic activity and maintaining PA homeostasis. These findings contribute to our understanding of the complex signaling network involved in plant immune responses. [Extracted from the article]