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Abstract Background Comparisons between endurance training (ET) and resistance training (RT) have produced equivocal findings in chronic obstructive pulmonary disease (COPD) patients. The purpose of our study is to investigate the effectiveness and long-term outcomes of adding ET and RT to conventional medical treatment in patients with COPD. A secondary objective is to investigate the clinical improvements resulting from exercise training in patients with different disease severities. Methods The study was a multicenter, prospective trial in people with stable COPD. The cohort was randomized to three groups: individualized medical treatment group (MT), MT + endurance training group (MT + ET) and MT + resistance training group (MT + RT). Exercise was performed 3 times weekly over a 12-week period. The endpoints of exercise capacity, health-related quality of life, COPD symptoms, lung function, and anxiety and depression questionnaires were re-evaluated at baseline, at the completion of the intervention and at 6 and 12-month follow-up. According to the COPD assessment tool offered by GOLD guidelines, patients were stratified into GOLD A and B groups and GOLD C and D groups for further subgroup analysis. Results The intention-to-treat (ITT) population included 366 patients, 328 of them completed the study protocol over 12 months (the PP-population). There were no significant differences in the primary outcome, quality of life, between patients who underwent medical treatment (MT) alone, MT + endurance training (MT + ET), or MT + resistance training (MT + RT) at the completion of the intervention, 6-, or 12-month follow-up. Additionally, no significant differences were observed between MT, MT + RT, or MT + ET groups concerning the primary outcome, exercise capacity (3MWD), after initial 3 months of intervention. However, a small statistically significant difference was noted in favor of MT + ET compared to MT + RT at 12 months (ITT: Δ3MWD in ET vs RT = 5.53 m, 95% confidence interval: 0.87 to 13.84 m, P = 0.03) (PP: Δ3MWD in ET vs RT = 7.67 m, 95% confidence interval: 0.93 to 16.27 m, P = 0.04). For patients in the GOLD C and D groups, improvement in quality of life following ET or RT was significantly superior to medical intervention alone. Furthermore, upon completion of the exercise regimen, RT exhibited a greater improvement in anxiety compared to ET in these patients (ITT: ΔHAD-A at 3-month: RT = -1.63 ± 0.31 vs ET = -0.61 ± 0.33, p

Purpose Performance status (PS), an essential indicator of patients’ functional abilities, is often documented in clinical notes of patients with cancer. The use of natural language processing (NLP) in extracting PS from electronic medical records (EMRs) has shown promise in enhancing clinical decision-making, patient monitoring, and research studies. We designed and validated a multi-institute NLP pipeline to automatically extract performance status from free-text patient notes. Patients and Methods We collected data from 19,481 patients in Harris Health System (HHS) and 333,862 patients from veteran affair’s corporate data warehouse (VA-CDW) and randomly selected 400 patients from each data source to train and validate (50%) and test (50%) the proposed pipeline. We designed an NLP pipeline using an expert-derived rule-based approach in conjunction with extensive post-processing to solidify its proficiency. To demonstrate the pipeline’s application, we tested the compliance of PS documentation suggested by the American Society of Clinical Oncology (ASCO) Quality Metric and investigated the potential disparity in PS reporting for stage IV non-small cell lung cancer (NSCLC). We used a logistic regression test, considering patients in terms of race/ethnicity, conversing language, marital status, and gender. Results The test results on the HHS cohort showed 92% accuracy, and on VA data demonstrated 98.5% accuracy. For stage IV NSCLC patients, the proposed pipeline achieved an accuracy of 98.5%. Furthermore, our analysis revealed a documentation rate of over 85% for PS among NSCLC patients, surpassing the ASCO Quality Metrics. No disparities were observed in the documentation of PS. Conclusion Our proposed NLP pipeline shows promising results in extracting PS from free-text notes from various health institutions. It may be used in longitudinal cancer data registries.

Abstract Osteoporosis, a metabolic bone disease characterized by low bone mineral density and deterioration of bone microarchitecture, has led to a high risk of fatal osteoporotic fractures worldwide. Accumulating evidence has revealed that sexual dimorphism is a notable feature of osteoporosis, with sex-specific differences in epidemiology and pathogenesis. Specifically, females are more susceptible than males to osteoporosis, while males are more prone to disability or death from the disease. To date, sex chromosome abnormalities and steroid hormones have been proven to contribute greatly to sexual dimorphism in osteoporosis by regulating the functions of bone cells. Understanding the sex-specific differences in osteoporosis and its related complications is essential for improving treatment strategies tailored to women and men. This literature review focuses on the mechanisms underlying sexual dimorphism in osteoporosis, mainly in a population of aging patients, chronic glucocorticoid administration, and diabetes. Moreover, we highlight the implications of sexual dimorphism for developing therapeutics and preventive strategies and screening approaches tailored to women and men. Additionally, the challenges in translating bench research to bedside treatments and future directions to overcome these obstacles will be discussed.

Abstract Huntington disease (HD) is a neurodegenerative disease caused by the abnormal expansion of a polyglutamine tract resulting from a mutation in the HTT gene. Oxidative stress has been identified as a significant contributing factor to the development of HD and other neurodegenerative diseases, and targeting anti-oxidative stress has emerged as a potential therapeutic approach. CHCHD2 is a mitochondria-related protein involved in regulating cell migration, anti-oxidative stress, and anti-apoptosis. Although CHCHD2 is highly expressed in HD cells, its specific role in the pathogenesis of HD remains uncertain. We postulate that the up-regulation of CHCHD2 in HD models represents a compensatory protective response against mitochondrial dysfunction and oxidative stress associated with HD. To investigate this hypothesis, we employed HD mouse striatal cells and human induced pluripotent stem cells (hiPSCs) as models to examine the effects of CHCHD2 overexpression (CHCHD2-OE) or knockdown (CHCHD2-KD) on the HD phenotype. Our findings demonstrate that CHCHD2 is crucial for maintaining cell survival in both HD mouse striatal cells and hiPSCs-derived neurons. Our study demonstrates that CHCHD2 up-regulation in HD serves as a compensatory protective response against oxidative stress, suggesting a potential anti-oxidative strategy for the treatment of HD.

Abstract Background and purpose Glucose-to-glycated hemoglobin ratio (GAR) is considered a more reliable marker of stress hyperglycemia by correcting for basal blood glucose levels. This study aimed to investigate the extent to which GAR is associated with 3 month and 1 year all-cause mortalities in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT). Methods We retrospectively followed 553 AIS patients who underwent MT. The degree of stress hyperglycemia was quantified as the GAR, defined as fasting plasma glucose (mmol/L)/hemoglobin A1c (HbA1c) (%) on the second day after admission. According to the GAR quartiles, the patients were further categorized into four groups (group 1-group 4). We assessed the association between GAR and all-cause mortalities, clinical outcomes during hospitalization and function outcomes at 3 months. The associations between stress hyperglycemia and all-cause mortalities were analyzed using a Cox proportional-hazards model, while other outcomes were analyzed using multiple logistic regression analysis. Results The follow-up lasted a median of 18 months (range 0–66 months). The 3 month mortality rate was 9.58% (n = 53) and the 1 year mortality rate was 18.62% (n = 103). The Kaplan–Meier analysis revealed a significant inverse relationship between GAR and mortality (P

Abstract Background and Aim To evaluate the efficacy and safety of minocycline, vonoprazan, amoxicillin, and bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment. Methods From August 2022 to May 2023, clinical data were collected from patients who received H. pylori eradication treatment at West China Fourth Hospital, Sichuan University. One group received the MVAB regimen (amoxicillin, minocycline, vonoprazan, and colloidal bismuth pectin), while another group received the FOAB regimen (amoxicillin, furazolidone, omeprazole, and colloidal bismuth pectin), both administered for 14 days. Follow‐up assessments of safety and compliance were conducted within 1 week after treatment completion. One and a half months after treatment, the success of eradication was evaluated using the urea breath test. Results For the MVAB regimen as a first‐line treatment, the eradication rate was 90.1% (127/141, 95% CI: 85.1–95.1%) in the ITT analysis and 93.4% (127/136, 95% CI: 89.2–97.6%) in the PP analysis as a first‐line treatment. As a second‐line treatment, the eradication rate was 91.3% (21/23, 95% CI: 78.8–103.8%) in both analyses. For the FOAB regimen as a first‐line treatment, the eradication rate was 98.0% (50/51, 95% CI: 94.1–101.2%) in the ITT analysis and 100% (50/50, 95% CI: 100%) in the PP analysis. As a second‐line treatment, the eradication rate was 100% (6/6, 95% CI: 100%) in both analyses. Moreover, there was no significant difference in the incidence of adverse events between the two groups (MVAB regimen: 5.5% and FOAB regimen: 8.8%; P > 0.05). Conclusions The MVAB regimen could indeed be a viable alternative treatment option to conventional therapies.

ObjectiveThis research aimed to elucidate the relationship between testosterone levels and serum soluble klotho (S-klotho) concentrations in females aged 40-79 years using the National Health and Nutrition Examination Survey (NHANES) dataset.DesignAssociations between testosterone and S-klotho were assessed through multivariable linear regression methodologies, spanning nonadjusted, minimally adjusted, and fully adjusted models.SettingsThe investigation was conducted as a cross-sectional analysis utilizing the NHANES database.ParticipantsFrom 20,146 NHANES participants between 2013 and 2016, 2,444 females met the stipulated inclusion and exclusion criteria.ResultsFree androgen index (FAI) showcased a negative correlation with S-klotho levels across all regression models (nonadjusted: β -7.08, 95% CI -13.39- -0.76; minimally adjusted: β -9.73, 95% CI -16.6- -2.84; fully adjusted: β -7.63, 95% CI -14.75-0.51). Conversely, total testosterone did not exhibit significant associations with S-klotho across the models. In the nonadjusted model, estradiol was positively associated with S-klotho concentrations (β 0.14, 95% CI 0.05-0.23), but this significance was not retained in subsequent regression models.ConclusionFindings suggest that in U.S. females aged 40-79 years, FAI negatively correlates with S-klotho concentrations, while there is the lack of significant associations for total testosterone and estradiol.

BackgroundAnxiety is common in patients with chronic obstructive pulmonary disease (COPD), especially in older patients with the definition of age over 60 years old. Few studies have focused on anxiety in older COPD patients. This study aimed to analyze the risk factors of anxiety in older COPD patients and the impacts of anxiety on future acute exacerbation.MethodsThe general information, questionnaire data, previous acute exacerbation and pulmonary function were collected. Hamilton Anxiety Rating Scale (HAMA) was used to evaluate the anxiety of older COPD patients. The patients were followed up for one year, the number and the degrees of acute exacerbations of COPD were recorded.ResultsA total of 424 older COPD patients were included in the analysis. 19.81% (N = 84) had anxiety symptoms, and 80.19% (N = 340) had no anxiety symptoms. There were increased pack-years, more comorbidities, and more previous acute exacerbations in older COPD patients with anxiety compared to those without anxiety (P < 0.05). Meanwhile, a higher modified Medical Research Council (mMRC), a higher COPD assessment test (CAT) score and a shorter six-minute walking distance (6MWD) were found in older COPD patients with anxiety (P < 0.05). The BODE index, mMRC, CAT score, comorbidities and acute exacerbations were associated with anxiety. Eventually, anxiety will increase the risk of future acute exacerbation in older COPD patients (OR = 4.250, 95% CI: 2.369–7.626).ConclusionOlder COPD patients with anxiety had worsening symptoms, more comorbidities and frequent acute exacerbation. Meanwhile, anxiety may increase the risk of acute exacerbation in the future. Therefore, interventions should be provided to reduce the risk of anxiety in older COPD patients at an early stage.

PurposeThis study aims to determine if the incubation after oocyte denudation before Intra-cytoplasmic sperm injection (ICSI) affects the clinical pregnancy rate.MethodsThis was a retrospective, consecutive data analysis of 1370 patients who underwent ICSI cycles at the Department of Reproductive Medicine of West China Second University of Sichuan University (Chengdu, Sichuan) between January 2020 and July 2022. The primary outcome was the clinical pregnancy rate. The second outcome included fertilization rate, biochemical pregnancy rate, and miscarriage rates.ResultsA total of 1370 continuous fresh transferred ICSI cycles were analyzed. Multivariate linear regression and logistic regression analysis of factors related to clinical pregnancy rates revealed that clinical pregnancy rates were significantly associated with denudation (DEN)-ICSI time interval. Long DEN-ICSI intervals are associated with a higher clinical pregnancy rate during fresh embryo transfer.ConclusionThe DEN-ICSI time interval is an independent factor for clinical outcomes in fresh ICSI transfer cycles.

Pancreatic adenocarcinoma (PDAC) is an aggressive tumor with poor survival and limited treatment options. PDAC resistance to immunotherapeutic strategies is multifactorial, but partially owed to an immunosuppressive tumor immune microenvironment (TiME). However, the PDAC TiME is heterogeneous and harbors favorable tumor-infiltrating lymphocyte (TIL) populations. Tertiary lymphoid structures (TLS) are organized aggregates of immune cells that develop within non-lymphoid tissue under chronic inflammation in multiple contexts, including cancers. Our current understanding of their role within the PDAC TiME remains limited; TLS are complex structures with multiple anatomic features such as location, density, and maturity that may impact clinical outcomes such as survival and therapy response in PDAC. Similarly, our understanding of methods to manipulate TLS is an actively developing field of research. TLS may function as anti-tumoral immune niches that can be leveraged as a therapeutic strategy to potentiate both existing chemotherapeutic regimens and potentiate future immune-based therapeutic strategies to improve patient outcomes. This review seeks to cover anatomy, relevant features, immune effects, translational significance, and future directions of understanding TLS within the context of PDAC.

This study delves into a profound exploration, using simple yet effective Monte Carlo ray‐tracing simulations, of the influence of the refractive indices of multiple quantum wells (MQWs) and p‐type electron blocking layer (p‐EBL) on the photon propagation and subsequent light extraction behavior in AlGaN‐based ultraviolet‐C (UVC) light‐emitting diodes (LEDs), covering both transverse‐electric (TE) and transverse‐magnetic (TM) polarized light. Remarkably, the refractive index contrasts at the heterointerfaces of p‐EBL/MQWs/n‐AlGaN have a relatively minor impact on the extraction efficiency of TE‐polarized light but exert a significant influence on TM‐polarized light. This discrepancy arises from the substantial effect of total internal reflection at these heterointerfaces on the propagation of photons emitted at large angles. Thus, this observation elucidates the oversight of photon propagation in the conventional design of MQWs and p‐EBL in AlGaN‐based UVA and UVB LEDs, where TE‐polarized emission predominates. Building upon simulation results, a highly effective strategy for extracting TM‐polarized light in AlGaN‐based UVC LEDs is further demonstrated by combining refractive index engineering with inclined sidewalls. The findings suggest refractive index engineering can serve as a novel design parameter for AlGaN‐based UVC LEDs dominated by TM‐polarized emission, expanding the range of techniques available for enhancing device performance.

Abstract The endometrium is a unique human tissue with an extraordinary ability to undergo a hormone‐regulated cycle encompassing shedding, bleeding, scarless repair, and regeneration throughout the female reproductive cycle. The cyclical repair and regeneration of the endometrium manifest as changes in endometrial epithelialization, glandular regeneration, and vascularization. The mechanisms encompass inflammation, coagulation, and fibrinolytic system balance. However, specific conditions such as endometriosis or TCRA treatment can disrupt the process of cyclical endometrial repair and regeneration. There is uncertainty about traditional clinical treatments' efficacy and side effects, and finding new therapeutic interventions is essential. Researchers have made substantial progress in the perspective of regenerative medicine toward maintaining cyclical endometrial repair and regeneration in recent years. Such progress encompasses the integration of biomaterials, tissue‐engineered scaffolds, stem cell therapies, and 3D printing. This review analyzes the mechanisms, diseases, and interventions associated with cyclical endometrial repair and regeneration. The review discusses the advantages and disadvantages of the regenerative interventions currently employed in clinical practice. Additionally, it highlights the significant advantages of regenerative medicine in this domain. Finally, we review stem cells and biologics among the available interventions in regenerative medicine, providing insights into future therapeutic strategies.

AbstractObjective To evaluate the effect of HIFU (High-Intensity Focused Ultrasound) therapy on the survival and prognosis of patients with inoperable pancreatic cancer, and the clinical application of serological prognostic indicators.Methods We retrospectively analyzed the clinicopathological features, laboratory tests and follow-ups of 192 patients. Among the patients, 57 were treated with HIFU prior to chemotherapy (HIFU-priority), and 135 patients received chemotherapy followed by HIFU (HIFU-second). Univariate and multivariate Cox regression analysis was used to determine the prognostic value of tumor inflammation-related serological markers. A nomogram model was established based on the identified prognostic factors.Results Univariate analysis showed that receiving the treatment regimen in HIFU-priority was a significant protective factor for overall survival (OS, p

Abstract Background Literature review have shown that sarcopenia substantially alters the postoperative outcomes after liver resection for malignant tumors. However, these retrospective studies do not distinguish cirrhotic and non-cirrhotic liver cancer patients, nor combine the assessment of muscle strength in addition to muscle mass. The purpose of this study is to study the relationship between sarcopenia and short-term outcomes after hepatectomy in patients with non-cirrhotic liver cancer. Methods From December 2020 to October 2021, 431 consecutive inpatients were prospectively enrolled in this study. Muscle strength and mass were assessed by handgrip strength and the skeletal muscle index (SMI) on preoperative computed tomographic scans, respectively. Based on the SMI and the handgrip strength, patients were divided into four groups: group A (low muscle mass and strength), group B (low muscle mass and normal muscle strength), group C (low muscle strength and normal muscle mass), and group D (normal muscle mass and strength). The main outcome was major complications and the secondary outcome was 90-d Readmission rate. Results After strictly exclusion, 171 non-cirrhosis patients (median age, 59.00 [IQR, 50.00–67.00] years; 72 females [42.1%]) were selected in the final analysis. Patients in group A had a statistically significantly higher incidence of major postoperative complications (Clavien–Dindo classification ≥ III) (26.1%, p = 0.032), blood transfusion rate (65.2%, p

Cancer treatment is hampered by resistance to conventional therapeutic strategies, including chemotherapy, immunotherapy, and targeted therapy. Redox homeostasis manipulation is one of the most effective innovative treatment techniques for overcoming drug resistance. Reactive oxygen species (ROS), previously considered intracellular byproducts of aerobic metabolism, are now known to regulate multiple signaling pathways as second messengers. Cancer cells cope with elevated amounts of ROS during therapy by upregulating the antioxidant system, enabling tumor therapeutic resistance via a variety of mechanisms. In this review, we aim to shed light on redox modification and signaling pathways that may contribute to therapeutic resistance. We summarized the molecular mechanisms by which redox signaling-regulated drug resistance, including altered drug efflux, action targets and metabolism, enhanced DNA damage repair, maintained stemness, and reshaped tumor microenvironment. A comprehensive understanding of these interrelationships should improve treatment efficacy from a fundamental and clinical research point of view.

Background and purposeStress hyperglycemia is common in critical and severe diseases. However, few studies have examined the association between stress hyperglycemia and the functional outcomes of patients with anterior circulation stroke, after mechanical thrombectomy (MT), in different diabetes status. This study therefore aimed to determine the relationship between stress hyperglycemia and the risk of adverse neurological functional outcomes in anterior circulation stroke patients with and without diabetes after MT.MethodsData of 408 patients with acute anterior circulation stroke treated with MT through the green-channel treatment system for emergency stroke at the First Affiliated Hospital of Jinan University between January 2016 and December 2020 were reviewed retrospectively. The stress hyperglycemia ratio (SHR) was calculated as fasting plasma glucose (mmol/L) divided by glycosylated hemoglobin (%). The patients were stratified into four groups by quartiles of SHR (Q1-Q4). The primary outcome was an excellent (nondisabled) functional outcome at 3 months after admission (modified Rankin Scale score of 0–1). The relationship between stress hyperglycemia and neurological outcome after stroke was assessed using multivariate logistic regression.ResultsAfter adjusting for potential confounders, compared with patients in Q1, those in Q4 were less likely to have an excellent outcome at 3 months (odds ratio [OR], 0.32, 95% confidence interval [CI], 0.14–0.66, p = 0.003), a good outcome at 3 months (OR, 0.41, 95% CI, 0.20–0.84, p = 0.020), and major neurological improvement (OR, 0.38, 95% CI, 0.19–0.73, p = 0.004). Severe stress hyperglycemia increased risks of 3-months all-cause mortality (OR, 2.82, 95% CI, 1.09–8.29, p = 0.041) and ICH (OR, 2.54, 95% CI, 1.21–5.50, p = 0.015).ConclusionStress hyperglycemia was associated with a reduced rate of excellent neurological outcomes, and increased mortality and ICH risks in patients with anterior circulation stroke after MT regardless of diabetes status.

Abstract Background Innate lymphoid cells (ILCs), as an important group of innate immunity, could respond rapidly to Mycobacterium tuberculosis (Mtb) infection. In this research, we studied the phenotypic changes of circulatory ILCs in active tuberculosis (TB) disease. Methods We recruited 40 patients with active Mtb infection (TB group) and 41 healthy subjects (NC group), and collected their clinical information and peripheral blood. Circulating ILCs, ILC subsets, dendritic cells (DCs), macrophages, and the production of cytokines in ILCs were tested by flow cytometry (FCM). Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma IL-23. Results Compared with healthy control, total ILCs (0.73% vs. 0.42%, P = 0.0019), ILC1 (0.55% vs. 0.31%, P = 0.0024) and CD117+ ILC2 (0.02% vs. 0.01%, P = 0.0267) were upregulated in TB group. The total IL-17+ lymphocytes were elevated (3.83% vs. 1.76%, P = 0.0006) while the IL-22+ lymphocytes remained unchanged. Within ILC subsets, ILC3, CD117+ ILC2 and ILC1 in TB group all expressed increased IL-17 (15.15% vs. 4.55%, 19.01% vs. 4.57%, 8.79% vs. 3.87%, P

It is said that in a synergistic relationship between vegetation and soil moisture (SM), the latter may be consumed excessively, while at the same time improving the ecological environment, such as in the large-scale artificial vegetation planting areas on the Loess Plateau. At present, the possibility of vegetation restoration and its impact on the water ecology of the Loess Plateau have received extensive attention. In this study, piecewise linear regression (PLR) and nonparametric conditional quantile regression (NCQR) models have been innovatively applied to vegetation survey data and soil moisture data from 50 field samples to explore the trade-off relationship between soil moisture and various vegetation parameters (VPs) and the response of soil moisture to the vegetation. The results showed that precipitation and topography are significantly linearly related to soil moisture in the sampling plots. Affected by irrational planting, the soil moisture benefit at 20–40 cm is significant weaker than that at 0–20 cm (plot 4, 5, 26 and 44). Some sampling plots excessively consumed soil water to promote vegetation planting. Although there was stronger soil water infiltration by shrubs, it was noted that the vegetation planting plan in some grass plots and shrub-grass plots were unreasonable and needed to be adjusted due to the clear risk of a soil water deficit determined by the trade-off values (represented by the root mean square deviation), plant species, a multiparameter evaluation. With the increase in soil moisture in the sampling plots, the negative correlation between the trade-off (soil moisture and vegetation) and soil moisture was transformed into a positive correlation (the inflection point was 8.5–10%). In addition, the benefit of soil moisture gradually changed from “shortage” to “appropriateness” and even “excess” (the inflection point was 15–20%). The fitting results of the two models are optimal and show clear applicability for evaluating trade-off relationships. Among the VPs involved in the calculation, the Shannon–Wiener index (H), Margarlef index (D1) and Fractional Vegetation Cover index (FVC) demonstrated better regional representation and stability.

N6-Methyladenosine-related long noncoding RNAs play an essential role in many cancers’ development. However, the relationship between m6A-related lncRNAs and acute myelogenous leukemia (AML) prognosis remains unclear. We systematically analyzed the association of m6A-related lncRNAs with the prognosis and tumor immune microenvironment (TME) features using the therapeutically applicable research to generate effective treatment (TARGET) database. We screened 315 lncRNAs associated with AML prognosis and identified nine key lncRNAs associated with m6A by the LASSO Cox analysis. A model was established based on these nine lncRNAs and the predictive power was explored in The Cancer Genome Atlas (TCGA) database. The areas under the ROC curve of TARGET and TCGA databases for ROC at 1, 3, and 5 years are 0.701, 0.704, and 0.696, and 0.587, 0.639, and 0.685, respectively. The nomogram and decision curve analysis (DCA) showed that the risk score was more accurate than other clinical indicators in evaluating patients’ prognoses. The clusters with a better prognosis enrich the AML pathways and immune-related pathways. We also found a close correlation between prognostic m6A-related lncRNAs and tumor immune cell infiltration. LAG3 expression at the immune checkpoint was lower in the worse prognostic cluster. In conclusion, m6A-related lncRNAs partly affected AML prognosis by remodeling the TME and affecting the anticarcinogenic ability of immune checkpoints, especially LAG3 inhibitors. The prognostic model constructed with nine key m6A-related lncRNAs can provide a method to assess the prognosis of AML patients in both adults and children.

Abstract Background It is reported that growth hormone (GH) can alleviate oxidative stress (OS) induced apoptosis in some types of cells by activating the PI3K/Akt signaling pathway. This study investigated the role and underlying mechanism of GH in OS and apoptosis in granulosa cells (GCs) of patients with polycystic ovary syndrome (PCOS). Methods Primary GCs were collected from patients with and without PCOS (controls, n = 32) during oocyte retrieval. The patients with PCOS were randomly assigned to take GH treatment (PCOS-GH, n = 30) or without GH treatment (PCOS-C, n = 31). Reactive oxygen species (ROS) level was determined by spectrophotometry and fluorescence microscopy. GC apoptosis and mitochondrial membrane potential (MMP) were detected by Annexin V-FITC/PI double-staining and JC-1 staining, respectively (flow cytometry). The expression of apoptosis-related genes and proteins involved in PI3K/Akt signaling was determined by quantitative reverse-transcription polymerase chain reaction and western blotting, while active caspase-9 and caspase-3 levels of GCs were determined by enzyme-linked immunosorbent assay. Results Our study found that in GCs of the PCOS-GH group, the ROS levels and apoptotic rates were significantly decreased, whereas MMP was significantly increased when compared to those in the PCOS-C group (P

Metastatic dissemination contributes to the lethality in pancreatic ductal adenocarcinoma (PDAC). Here, the authors perform RNA-sequencing on patient derived circulating tumor cells (CTCs) and identify three major CTC subgroups, and show the therapeutic potential of targeting LIN28B/let-7 pathway to halt cancer metastasis.

The aim is to diagnose COVID-19 earlier and to improve its treatment by applying medical technology, the “COVID-19 Intelligent Diagnosis and Treatment Assistant Program (nCapp)” based on the Internet of Things. Terminal eight functions can be implemented in real-time online communication with the “cloud” through the page selection key. According to existing data, questionnaires, and check results, the diagnosis is automatically generated as confirmed, suspected, or suspicious of 2019 novel coronavirus (2019-nCoV) infection. It classifies patients into mild, moderate, severe or critical pneumonia. nCapp can also establish an online COVID-19 real-time update database, and it updates the model of diagnosis in real time based on the latest real-world case data to improve diagnostic accuracy. Additionally, nCapp can guide treatment. Front-line physicians, experts, and managers are linked to perform consultation and prevention. nCapp also contributes to the long-term follow-up of patients with COVID-19. The ultimate goal is to enable different levels of COVID-19 diagnosis and treatment among different doctors from different hospitals to upgrade to the national and international through the intelligent assistance of the nCapp system. In this way, we can block disease transmission, avoid physician infection, and epidemic prevention and control as soon as possible.

BackgroundSome female thyroid cancer survivors wish to become pregnant following their cancer treatment. Current studies have shown inconsistent results on pregnancy outcomes in these survivors; however, detailed information on the pathological type, treatment, and gestational thyroid function of these patients are not yet well documented, making the refined assessment of the influence of a history of thyroid cancer and related treatments on pregnancy outcomes challenging.ObjectiveTo investigate the risk of adverse pregnancy outcomes in thyroid cancer survivors.MethodsThis was a retrospective cohort study. We included all women aged between 19 and 45 years old who delivered between January 2019 and June 2020 in West China Second University Hospital of Sichuan University. Women with tumors other than thyroid cancer or other thyroid diseases were excluded. The included women were divided into survivors of thyroid cancer (survivors) and women without any history of thyroid disease (controls). Propensity score matching and logistic regression were used to control confounding variables.ResultsAll 18,332 women who met the inclusion criteria were included in the study (96 survivors of papillary thyroid cancer and 18,236 controls). After propensity score matching, 96 survivors and 192 controls were included. The survivors had higher levels of free thyroxine (15.47 [13.61–17.67] vs. 14.38 [13.20–15.81] pmol/mL; P

We first reported that the Hippo-YAP signaling pathway plays a critical role in the pathogenesis of endometriosis (EMS). Autophagy is also related to the invasion ability of endometrial cells and is involved in the pathogenesis of EMS through multi-levels. However, the precise regulatory mechanism of YAP on autophagy in the eutopic endometrial stromal cells (ESCs) is still unclear. Primary eutopic ESCs of EMS patients (n = 12) and control patients without EMS (n = 9) were isolated and cultured to investigate the expressions of YAP and mTOR, the role of YAP in autophagy, and the effect of the YAP-autophagy signal on the decidualization of the eutopic ESCs. Endometriosis-related sequencing data (GSE51981) in the GEO database were used to find the genes significantly correlated with YAP. We found 155 genes with significant differences in the interaction with YAP in EMS from the dataset, and the autophagy pathway was significantly enriched. Following on from our previous studies of YAP knockdown, overexpression of YAP resulted in an increased expression of mTOR and decreased ratio of LC3-II/LC3-I and autophagy markers, in the eutopic ESCs; transmission electron microscope observation also showed fewer autophagosomes compared with the control cells. Furthermore, ESCs of the Rapamycin-treated group showed significant decidual-like changes with significantly increased decidual prolactin level at 72 h after in vitro decidualization. These results demonstrate that the increased YAP inhibited the level of autophagy by upregulating the mTOR signal in the eutopic ESCs of endometriosis. The YAP-autophagy signal plays an important role in the pathogenesis of endometriosis-associated infertility.

PurposePatients with cancer often have compromised immune system which can lead to worse COVID-19 outcomes. The purpose of this study is to assess the association between COVID-19 outcomes and existing cancer-specific characteristics.Patients and methodsPatients aged 18 or older with laboratory-confirmed COVID-19 between June 1, 2020, and December 31, 2020, were identified (n = 314 004) from the Optum® de-identified COVID-19 Electronic Health Record (EHR) derived from more than 700 hospitals and 7000 clinics in the United States. To allow sufficient observational time, patients with less than one year of medical history in the EHR dataset before their COVID-19 tests were excluded (n = 42 365). Assessed COVID-19 outcomes including all-cause 30-day mortality, hospitalization, ICU admission, and ventilator use, which were compared using relative risks (RRs) according to cancer status and treatments.ResultsAmong 271 639 patients with COVID-19, 18 460 had at least one cancer diagnosis: 8034 with a history of cancer and 10 426 with newly diagnosed cancer within one year of COVID-19 infection. Patients with a cancer diagnosis were older and more likely to be male, white, Medicare beneficiaries, and have higher prevalences of chronic conditions. Cancer patients had higher risks for 30-day mortality (RR 1.07, 95% CI 1.01-1.14, P = 0.028) and hospitalization (RR 1.04, 95% CI 1.01-1.07, P = 0.006) but without significant differences in ICU admission and ventilator use compared to non-cancer patients. Recent cancer diagnoses were associated with higher risks for worse COVID-19 outcomes (RR for mortality 1.17, 95% CI 1.08-1.25, PConclusions and relevanceIndividuals with cancer had higher risks for 30-day mortality and hospitalization after SARS-CoV-2 infection compared to patients without cancer. More specifically, patients with a cancer diagnosis within 1 year and those receiving active treatment were more vulnerable to worse COVID-19 outcomes.

Abstract Background Neoadjuvant chemotherapy (NAC) is frequently used in gastrointestinal cancers (GIC), and pathological, radiological, and tumor marker responses are assessed during and after NAC. Aim To evaluate the relationship between pathologic, radiologic, tumor marker responses and recurrence‐free survival (RFS), overall survival (OS), adjuvant chemotherapy (AC) decisions, and the impact of changing to a different AC regimen after poor response to NAC. Methods and results Medical records of GIC patients treated with NAC at Mount Sinai between 1/2012 and 12/2018 were reviewed. One hundred fifty‐six patients (58.3% male, mean age 63 years) were identified. Primary tumor sites were: 43 (27.7%) pancreas, 62 (39.7%) gastroesophageal, and 51 (32.7%) colorectal. After NAC, 31 (19.9%) patients had favorable pathologic response (FPR; defined as College of American Pathologists [CAP] score 0–1). Of 107 patients with radiological data, 59 (55.1%) had an objective response, and of 113 patients with tumor marker data, 61 (54.0%) had a ≥50% reduction post NAC. FPR, but not radiographic or serological responses, was associated with improved RFS (HR 0.28; 95% CI 0.11–0.72) and OS (HR 0.13; 95% CI 0.2–0.94). Changing to a different AC regimen from initial NAC, among all patients and specifically among those with unfavorable pathological response (UPR; defined as CAP score 2–3) after NAC, was not associated with improved RFS or OS. Conclusions GIC patients with FPR after NAC experienced significant improvements in RFS and OS. Patients with UPR did not benefit from changing AC. Prospective studies to better understand the role of pathological response in AC decisions and outcomes in GIC patients are needed.

Objective: This work was conducted in order to study the effect of the lower genital tract (vaginal and cervical canal) microbiota on pregnancy outcomes of reproductive-aged women receiving embryo transfer.Study design: A total of 150 reproductive-aged patients who received the first fresh in vitro fertilization-embryo transfer (IVF-ET) were included in the study. Samples from the vagina and cervical site of each patient were collected separately using sterile swabs before ET. Genomic DNA was pyrosequenced for the V3–V4 regions of the 16S ribosomal RNA gene. Further bioinformatics analysis was performed using QIIME and R package. Pregnancy outcomes were followed and analyzed to compare differences in microbial composition.Results: The cervical microbiota had a higher Shannon index than the vaginal microbiota, and the microbial composition was different between the two sites. However, the Sorenson index between the two sites within the same individual was 0.370 (0.309–0.400). A total of 89 patients achieved clinical pregnancy after ET, while 61 failed. The Shannon indices and the microbial community of both vaginal and cervical microbiota between pregnant and non-pregnant groups were not significantly different. The relative abundance of Lactobacillus in the vagina and cervical canal did not differ between the two groups. Linear discriminant analysis, random forest analysis, and receiver-operating characteristic curve analysis showed that Bifidobacterium, Prevotella, and Lactobacillus iners in the vagina, as well as Solanum torvum, Fusobacterium, and Streptococcus in the cervix, may be negatively associated with clinical pregnancy after IVF.Conclusion: The cervical microbiota was more diverse than the vaginal microbiota, but because of anatomical continuity, there was a correlation between the two sites. The microbial composition of the vagina and cervical canal may influence the outcome of IVF-ET, but more samples are needed to verify this conclusion.

Used Random forest algorithm to construct a prediction model of aroma components based on the hybrid offspring of ‘Honeycrisp’ × ‘Maodi’, and different preprocessing methods were tried (Standardization (SS), First-order Derivative (D1) and Standard normal variate (SNV)). The aroma composition and content were determined by gas chromatography-mass spectrometry (GC-MS), and the main aroma components of apples were classified according to compound categories, including ester, aldehyde, ketone, alcohol. Taking the chemical groups as the research objects, the characteristic wavelengths were selected by grid search algorithm, and the characteristic wavelength-aroma chemical group model was established, and the same method was used to construct the model for single aroma components. The results show: SNV has the best noise removal effect among the five preprocessing methods. Under the SNV treatment, aroma chemical groups of apples showed a good correlation with the spectrum. The number of characteristic spectra of ester are 413, 493, 512, 551, 592, 600, 721, 727, 729, 733 nm, all in the visible light range. The determination coefficient (R2), the root mean square error (RMSE) and the ratio of the standard deviation values (RPD) of validation were 0.90, 4936.16 and 1.13. The characteristic spectrum of alcohols is 519, 562, 570, 571, 660, 676, 737, 738 nm, the range is close to that of ester. The R2 and RMSE of alcohol validation are 0.92 and 83.21, and RPD is 1.30. The number of characteristic spectra of aldehyde is 20, and the most important band is 1000 nm, which is outside the visible light range. The number of characteristic spectra of ketone is 15, and also has some distribution outside the visible light range. The R2 of aldehyde and ketone validation are 0.84 and 0.86. Except for cyclooctanol, the R2 of single aroma compound prediction model performed poorly. Based on the models, we tried to visualize alcohol, which can roughly represent their distribution on apple. Their distributions all show significant differences in the center and edge of apple, but the results are still rough due to the accuracy of models. In conclusion, the study can preliminarily prove that hyperspectral imaging technology (HSI) can perform non-destructive detection of aroma in apple hybrid offspring.

Apples are a rich source of polyphenols in the human diet. However, the distribution of polyphenols in different apple varieties and tissues is still largely unclear. In this study, a new liquid chromatography–tandem mass spectrometry (LC-MS/MS) strategy was developed to reveal the spatial distribution of polyphenols in different apple tissues and varieties. A method based on multiple reaction monitoring (MRM)-enhanced product ion (EPI) was established in the information-dependent acquisition (IDA) mode for pseudo-target screening of major apple polyphenols. A total of 39 apple polyphenolic metabolites were finally identified. Qualitative and quantitative results showed that the variety and content of polyphenols in apple peels were higher than those of other tissues. In apple roots, stems, and leaves, the highest polyphenol variety and content were found in wild species, followed by cultivars and elite varieties. Dihydrochalcone substances, one kind of major apple polyphenols, were more abundant in apple roots, stems, and leaves. This strategy can be applied as a model for other agricultural products, in addition to revealing the distribution of polyphenols in different tissues of apples, which provides a theoretical basis for the utilization of polyphenol resources and variety selection.

BackgroundStudies have shown that N6-methyl adenosine (m6A) plays an important role in cancer progression; however, the underlying mechanism of m6A modification in tumor microenvironment (TME) cell infiltration of bladder cancer remains unclear. This study aimed to investigate the role of m6A modification in TME cell infiltration of bladder cancer.MethodsThe RNA expression profile and clinical data of bladder cancer were obtained from The Cancer Genome Atlas and Gene Expression Omnibus. We assessed the m6A modification patterns of 664 bladder cancer samples based on 20 m6A regulators through unsupervised clustering analysis and systematically linked m6A modification patterns to TME cell infiltration characteristics. Gene ontology and gene set variation analyses were conducted to analyze the underlying mechanism based on the assessment of m6A methylation regulators. Principal component analysis was used to construct the m6A score to quantify m6A modification patterns of bladder cancer.ResultsThe genetic and expression alterations in m6A regulators were highly heterogeneous between normal and bladder tissues. Three m6A modification patterns were identified. The cell infiltration characteristics were highly consistent with the three immune phenotypes, including immune rejection, immune inflammation, and immune desert. The biological functions of three m6A modification patterns were different. Cox regression analyses revealed that the m6A score was an independent signature with patient prognosis (HR = 1.198, 95% CI: 1.031–1.390). Patients with a low-m6A score were characterized by increased tumor mutation burden, PD-L1 expression, and poorer survival. Patients in the low-m6A score group also showed significant immune responses and clinical benefits in the CTLA-4 immunotherapy cohort (p =0.0069).ConclusionsThe m6A methylation modification was related to the formation of TME heterogeneity and complexity. Assessing the m6A modification pattern of individual bladder cancer will improve the understanding of TME infiltration characteristics.

Streptococcus suis (S. suis) type 2 (SS2) is an important zoonotic pathogen that causes swine streptococcosis, a widespread infectious disease that occurs in pig production areas worldwide and causes serious economic losses in the pork industry. Hosts recognize pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRRs) to activate both innate and acquired immune responses. However, S. suis has evolved multiple mechanisms to escape host defenses. Pathogenic proteins, such as enolase, double-component regulatory systems, factor H-combining proteins and other pathogenic and virulence factors, contribute to immune escape by evading host phagocytosis, reactive oxygen species (ROS), complement-mediated immune destruction, etc. SS2 can prevent neutrophil extracellular trap (NET) formation to avoid being trapped by porcine neutrophils and disintegrate host immunoglobulins via IgA1 hydrolases and IgM proteases. Currently, the pathogenesis of arthritis and meningitis caused by SS2 infection remains unclear, and further studies are necessary to elucidate it. Understanding immune evasion mechanisms after SS2 infection is important for developing high-efficiency vaccines and targeted drugs. Keywords: Streptococcus suis serotype 2, Virulence factor, Immune escape, Pathogenesis

Abstract Background Cryptosporidium parvum is an important zoonotic parasitic disease worldwide, but the molecular mechanisms of the host–parasite interaction are not fully understood. Noncoding microRNAs (miRNAs) are considered key regulators of parasitic diseases. Therefore, we used microarray, qPCR, and bioinformatic analyses to investigate the intestinal epithelial miRNA expression profile after Cryptosporidium parvum infection. Results Twenty miRNAs were differentially expressed after infection (four upregulated and 16 downregulated). Further analysis of the differentially expressed miRNAs revealed that many important cellular responses were triggered by Cryptosporidium parvum infection, including cell apoptosis and the inflammatory and immune responses. Conclusions This study demonstrates for the first time that the miRNA expression profile of human intestinal epithelium cells is altered by C. parvum infection. This dysregulation of miRNA expression may contribute to the regulation of host biological processes in response to C. parvum infection, including cell apoptosis and the immune responses. These results provide new insight into the regulatory mechanisms of host miRNAs during cryptosporidiosis, which may offer potential targets for future C. parvum control strategies.

Background: Antibiotic exposure has been associated with worse outcomes with immune checkpoint inhibitors (ICIs) in cancer patients, likely due to disruption of the gut microbiome. Other commonly prescribed medications, such as proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs), are also known to disrupt the microbiome, but data on their association with ICI outcomes are conflicting. Methods: We conducted a retrospective, multicenter, international cohort study including 314 hepatocellular carcinoma (HCC) patients treated with ICIs from 2017 to 2019 to assess the association between PPI or H2RA exposure (up to 30 days before ICI) and overall survival. Secondary outcomes included overall response rate (ORR) and development of any treatment-related adverse events (AEs). Results: Baseline PPI/H2RA exposure was not associated with overall survival in univariable (HR 1.01, 95% CI 0.75–1.35) or multivariable analysis (HR 0.98, 95% CI 0.71–1.36). Baseline PPI/H2RA exposure was not associated with either ORR (OR 1.32, 95% CI 0.66–2.65) or AEs (OR 1.07, 95% CI 0.54–2.12) in multivariable analysis. Conclusions: Our results suggest that exposure to PPI/H2RA prior to ICIs does not adversely affect outcomes in HCC patients.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by airway limitation accompanied with infiltration of inflammatory cells. Mucosal associated invariant T (MAIT) cells can recognize bacteria and play an important role in controlling host immune responses by producing cytokines. In this study, we characterized the function and the ability of MAIT cells to secrete cytokines measured by flow cytometry. In COPD patients, MAIT cells have the ability to produce more IL-17 and less IFN-γ compared to healthy individuals. We found that HLA-DR expression levels reflected the degree of inflammation and the proportion of IL-17 was significantly correlated with lung function in peripheral blood. In addition, we found that MAIT cells were highly expressed in the lung, and the increased expression of CXCR2, CXCL1 indicated that MAIT cells had the potential to migrate to inflammatory tissues. This evidence implies that MAIT cells may play a potential role in COPD immunopathology.

Gallotannins (GTs) are a series of hydrolyzable tannins with multiple health-promoting effects. In this study, an integrated liquid chromatography tandem mass spectrometry (LC–MS/MS) strategy was developed for unveiling the spatial distribution pattern of GTs in the emerging oilseed crops Paeonia rockii and P. ostii. According to the fragmentation behavior of the representative GT (1,2,3,4,6-penta-O-galloyl-β-D-glucose, PGG), the diagnostic neutral loss (NL) of 170 Da was chosen for the non-targeted screening of GT precursors. Simultaneously, the tandem mass spectrometry spectrum (MS/MS) information was acquired through an enhanced product ion (EPI) scan. Nine major GTs were identified in tree peony. To quantify the targeted GTs in different tissues of tree peony, we established a multiple reaction monitoring (MRM)–enhanced product ion (EPI)-based pseudo-targeted approach under the information-dependent acquisition (IDA) mode. The quantitative results show that the GT compounds were ubiquitous in tree peony plants with diverse structures. The typical GT PGG was mainly distributed in roots, leaves, and petals. This strategy can also be utilized for metabolite characterization and quantification in other substrates.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and systemic inflammatory processes, and exacerbation of COPD represents a critical moment in the progression of COPD. Several biomarkers of inflammation have been proposed to have a predictive function in acute exacerbation. However, their use is still limited in routine clinical practice. The purpose of our study is to explore the prognostic efficacy of novel inflammatory hemogram indexes in the exacerbation among stable COPD patients.Method: A total of 275 stable COPD patients from the Shanghai COPD Investigation Comorbidity Program were analyzed in our study. Blood examinations, especially ratio indexes like platelet–lymphocyte ratio (PLR), platelet × neutrophil/lymphocyte ratio [systemic immune-inflammation index (SII)], and monocyte × neutrophil/lymphocyte ratio [systemic inflammation response index (SIRI)], lung function test, CT scans, and questionnaires were performed at baseline and routine follow-ups. Clinical characteristics and information of exacerbations were collected every 6 months. The relationship between hemogram indexes and diverse degrees of exacerbation was assessed by logistic regression. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the ability of hemogram indexes to predict exacerbation of COPD. Furthermore, the discrimination and accuracy of combined indexes were measured by ROC and calibration curve.Result: There was a significant positive correlation between PLR levels and total exacerbation of COPD patients in a stable stage in a year. Also, the predictive ability of PLR exceeded any other ratio indexes, with an AUC of 0.66. SII and SIRI ranked second only to PLR, with an AUC of 0.64. When combining PLR with other indexes (sex, COPD year, and St. George's Respiratory Questionnaire scores), they were considered as the most suitable panel of index to predict total exacerbation. Based on the result of the ROC curve and calibration curve, the combination shows optimal discrimination and accuracy to predict exacerbation events in COPD patients.Conclusion: The hemogram indexes PLR, SII, and SIRI were associated with COPD exacerbation. Moreover, the prediction capacity of exacerbation was significantly elevated after combining inflammatory hemogram index PLR with other indexes, which will make it a promisingly simple and effective marker to predict exacerbation in patients with stable COPD.

Abstract Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) are standard treatment for advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation. However, EGFR mutation testing is not attainable in approximately 20% of patients. The current study examined intercalating and maintaining gefitinib treatment in stage IIIB/IV non-squamous NSCLC, never or former light smoking patients with unknown EGFR mutation status. Briefly, 219 patients who achieved stable disease (SD) with gemcitabine (1250 mg/m2) plus carboplatin (5 AUC) were randomized at 1:1 ratio to continue chemotherapy (n = 110) or intercalating gefitinib (250 mg/day on days 15–25 of each cycle until disease progress (n = 109). Progression-free survival (PFS) was 9.7 vs. 4.2 month in the gefitinib vs. control arm (HR: 0.41, 95% CI: 0.31–0.56; P

Abstract Background Enterocytozoon bieneusi is the dominant specie of microsporidia which can infect both anthroponotic and zoonotic species. The golden snub-nosed monkey is an endangered primate which can also infect by E. bieneusi. To date, few genetic data on E. bieneusi from golden snub-nosed monkeys has been published. Therefore, to clarify the prevalence and genotypes of E. bieneusi in captive golden snub-nosed monkeys is necessary to assess the potential for zoonotic transmission. Result We examined 160 golden snub-nosed monkeys from six zoos in four cities in China, using PCR and comparative sequence analysis of the ribosomal internal transcribed spacer (ITS). The overall prevalence of E. bieneusi was 46.2% (74/160); while the prevalence was 26.7%, 69.1%, 69.4% and 33.3% in Shanghai Zoo, Shanghai Wild Animal Park, Tongling Zoo, and Taiyuan Zoo respectively (P = 0.006). A total of seven E. bieneusi genotypes were found that included four known (D, J, CHG1, and CHG14) and three new (CM19–CM 21) genotypes. The most common genotype was D (54/74, 73.0%), followed by J (14/74, 18.9%); other genotypes were restricted to one or two samples. Phylogenetic analysis revealed that genotype D belonged to the previously-characterized Group 1, with zoonotic potential; whereas genotypes J, CHG1, CHG14 and CM19–CM 21 clustered in the previously-characterized Group 2, the so-called cattle host specificity group. Conclusions The findings of high prevalence of zoonotic E. bieneusi genotypes D and J in golden snub-nosed monkeys suggest that golden snub-nosed monkeys may be the reservoir hosts for human microsporidiosis, and vice versa.

We propose a simple and effective even-power fast algorithm to obtain scalable fringe precision in self-mixing interference. In this letter, the principle of the even-power fast algorithm is introduced in detail. The validity of the proposed algorithm is demonstrated by means of simulated signals and confirmed by experimental measurements at different vibration amplitudes. Without adding any additional optical elements in the optical path, theoretical analysis shows that the resolution of the fringe could be enhanced to λ/2n+3 (n = 0, 1, 2, 3. . .). Experimental results show a fringe precision of λ/32 is achieved at a sampling rate of 50 KS/s. The influence factors are also discussed when the algorithm is applied in actual measurements.

Background and Purpose: It is urgently required to develop promising candidates to permeate across blood-brain barrier (BBB) efficiently with simultaneous disrupting vasculogenic mimicry capability of gliomas. Previously, a series of iron (II) complexes were synthesized through a modified method. Hence, the aim of this study was to evaluate anticancer activity of Fe(PIP)3SO4 against glioma cancer cells.Methods: Cytotoxic effects were determined via MTT assay, and IC50 values were utilized to evaluate the cytotoxicity. Cellular uptake of Fe(PIP)3SO4 between U87 and HEB cells was conducted by subtracting content of the complex remaining in the cell culture supernatants. Propidium Iodide (PI)-flow cytometric analysis was used to analyze cell cycle proportion of U87 cells treated with Fe(PIP)3SO4. The reactive oxygen species levels induced by Fe(PIP)3SO4 were measured by 2'-deoxycoformycin (DCF) probe; ABTS assay was utilized to examine the radical scavenge capacity of Fe(PIP)3SO4. To study the bind efficiency to thioredoxin reductase (TrxR), Fe(PIP)3SO4 was introduced into solution containing TrxR. To verify if Fe(PIP)3SO4 could penetrate BBB, HBMEC/U87 coculture as BBB model was established, and penetrating capability of Fe(PIP)3SO4 was tested. In vitro U87 tumor spheroids were formed to test the permeating ability of Fe(PIP)3SO4. Acute toxicity and biodistribution of Fe(PIP)3SO4 were tested on mice for 72 h. Protein profiles associated with U87 cells treated with Fe(PIP)3SO4 were determined by Western blotting analysis.Results: Results showed that Fe(PIP)3SO4 could suppress cell proliferation by inducing G2/M phase cycle retardation and apoptotic pathways, which was related with expression of p53 and initiation factor 4E binding protein 1. In addition, Fe complex could suppress cell proliferation by downregulating reactive oxygen species levels via scavenging free radicals and interaction with TrxR. Furthermore, Fe(PIP)3SO4 could permeate across BBB and simultaneously inhibited the vasculogenic mimicry-channel of U87 cells, suggesting favorable antiglioblastoma efficacy. Acute toxicity manifested lower degree of the complex compared with cisplatin and temozolomide.Conclusion: Fe(PIP)3SO4 exhibited favorable anticancer activity against glioma cells associated with p53 and 4E binding protein 1, accompanied with negligible toxic effects on normal tissues. Herein, Fe(PIP)3SO4 could be developed as a promising metal-based chemotherapeutic agent to overcome BBB and antagonize glioblastomas.

Litchi is an important fruit cultivated in tropical and subtropical areas with high nutritious and delicious flavor and the pulp is the main part of the fruit consumed. Previous studies found that litchi had high total phenol content and antioxidant activity, but most of them focused on the identification of single or a few phenolic components with a low throughput test, and the metabolic differences of cultivars are still unknown to a some extent. In this study we used widely targeted metabolome based on ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS) to analyze the polyphenol metabolites of five different genotypes of mature litchi fruit. A total of 126 polyphenol metabolites in eight categories were identified to reveal the composition and differences of polyphenol; 15 common differential metabolites and 20 specific differential metabolites to each cultivar were found for the first time. The results infer that flavonoids, flavonols, hydroxycinnamoyls and catechins are the main polyphenol metabolites of litchi pulp. Cluster analysis showed that there were three groups of polyphenols from high to low; early maturing Feizhixiao is a kind of high polyphenol content cultivars, especially in catechins, anthocyanins, flavonols, quinic acids and hydroxycinnamoyls. The polyphenols in the flesh of mature litchi are rich, and there are significant differences among cultivars; there was a level of correlation between the contents of phenolics and the maturity of litchi cultivars; the content of phenolics in early maturing litchi cultivars appeared higher than those of mid- to late-maturing cultivars. This experiment will provide significant reference information for cultivation, breeding, processing and consumption.

Circulating tumor cells (CTCs) are shed from primary tumors into the bloodstream, mediating the hematogenous spread of cancer to distant organs. To define their composition, we compared genome-wide expression profiles of CTCs with matched primary tumors in a mouse model of pancreatic cancer, isolating individual CTCs using epitope-independent microfluidic capture, followed by single-cell RNA sequencing. CTCs clustered separately from primary tumors and tumor-derived cell lines, showing low-proliferative signatures, enrichment for the stem-cell-associated gene Aldh1a2, biphenotypic expression of epithelial and mesenchymal markers, and expression of Igfbp5, a gene transcript enriched at the epithelial-stromal interface. Mouse as well as human pancreatic CTCs exhibit a very high expression of stromal-derived extracellular matrix (ECM) proteins, including SPARC, whose knockdown in cancer cells suppresses cell migration and invasiveness. The aberrant expression by CTCs of stromal ECM genes points to their contribution of microenvironmental signals for the spread of cancer to distant organs.

Two Cryptosporidium isolates from separate infants suffering from diarrhea were obtained from a hospital in Zhengzhou, China and were genotyped by PCR amplification and sequence analysis of the small-subunit ribosomal RNA (rRNA) (SSU rRNA), 70-kDa heat shock protein (HSP70), and actin genes. Further subtyping was performed by PCR amplification and sequence analysis of the 60-kDa glycoprotein (gp60) gene. Both the isolates were identified as Cryptosporidium hominis subtype IdA21, a rare subtype previously found only in a human immunodeficiency virus-infected child in South Africa and another child in Jordan.