Enhanced hydrolysis and methane yield of temperature-phased dewatered sludge anaerobic digestion by microbial electrolysis cell.

Temperature-phased anaerobic digestion (TPAD) and microbial electrolysis cell (MEC) are both able to improve hydrolysis and methane yield during anaerobic digestion (AD) of dewatered sludge. However, the effect of TPAD and MEC integration at different temperatures and different phases is unclear. This study investigated the effect of the integration of intermittent energization MEC in different phases of TPAD on the digestion of dewatered sludge. Thermophilic and MEC hydrolysis could release higher total ammonia nitrogen of 186.0% and 10.3% than control, mesophilic methanogenesis phase integrated with MEC relieved the ammonia inhibition and accelerated the acid utilization leading to the relief of acid accumulation. The ultimate methane yield of the TPAD integrated with MEC was increased by 118.9%, in which the relative abundance of Methanothermobacteria and Methanosarcina was increased. Therefore, intermittent energization MEC integrated TPAD synchronously improved the hydrolysis and methane yield.

Identification of immune characteristic biomarkers and therapeutic targets in cuproptosis for sepsis by integrated bioinformatics analysis and single-cell RNA sequencing analysis.

Background: Cuproptosis is a copper-dependent cell death that is connected to the development and immune response of multiple diseases. However, the function of cuproptosis in the immune characteristics of sepsis remains unclear. Method: We obtained two sepsis datasets (GSE9960 and GSE134347) from the GEO database and classified the raw data with R packages. Cuproptosis-related genes were manually curated, and differentially expressed cuproptosis-related genes (DECuGs) were identified. Afterwards, we applied enrichment analysis and identified key DECuGs by performing machine learning techniques. Then, the immune cell infiltrations and correlation between DECuGs and immunocyte features were created by the CIBERSORT algorithm. Subsequently, unsupervised hierarchical clustering analysis was performed based on key DECuGs. We then constructed a ceRNA network based on key DECuGs by using multi-step computational strategies and predicted potential drugs in the DrugBank database. Finally, the role of these key genes in immune cells was validated at the single-cell RNA level between septic patients and healthy controls. Results: Overall, 16 DECuGs were obtained, and most of them had lower expression levels in sepsis samples. Afterwards, we obtained six key DECuGs by performing machine learning. Then, the LIPT1-T-cell CD4 memory resting was the most positively correlated DECuG-immunocyte pair. Subsequently, two different subclusters were identified by six DECuGs. Bioinformatics analysis revealed that there were different immune characteristics between the two subclusters. Moreover, we identified the key lncRNA OIP5-AS1 within the ceRNA network and obtained 4 drugs that may represent novel drugs for sepsis. Finally, these key DECuGs were statistically significantly dysregulated in another validation set and showed a major distribution in monocytes, T cells, B cells, NK cells and platelets at the single-cell RNA level. Conclusion: These findings suggest that cuproptosis might promote the progression of sepsis by affecting the immune system and metabolic dysfunction, which provides a new direction for understanding potential pathogenic processes and therapeutic targets in sepsis.

Nanobubble water promotes anaerobic digestion of high-solids cattle manure under mesophilic and thermophilic conditions.

The gradual increase in cattle farming has led to a huge production of cattle manure (CM), but the conventional treatment methods are less efficient. In this study, the treatment method of anaerobic digestion (AD) of high-solids CM by combining nanobubble water (NBW) with different gases was proposed to present a new idea for the reduction, harmlessness, and resourcefulness of CM. It was found that the performance of the digester with added NBW was better than the control. Among them, the cumulative methane yield T-Air: 227.09 mL g-1 VSadded and T-CO2: 226.12 mL g-1 VSadded increased by 17.72 % and 17.22 %, respectively, compared with the control T: 192.90 mL g-1 VSadded under thermophilic conditions. Under mesophilic conditions, M-Air: 162.39 mL g-1 VSadded increased by 9.68 % compared with control M: 148.05 mL g-1 VSadded. Microbial communities analyzed at the genus level revealed that the relative abundance of bacteria favorable to hydrolysis and acid-producing processes, such as Defluviitalea, Haloplasma, and Bacillus, increased to varying degrees. Moreover, the relative abundance of archaea favorable for methanogenesis, such as Methanoculleus, Methanobrevibacter, and Methanosarcina, also increased to varying degrees. Therefore, the addition of NBW promoted the hydrolysis of high-solids CM, enhanced the stability of the reaction, improved the methanogenic performance, and increased the RA of favorable genera, which ultimately led to a better performance of the AD of high-solids CM.

Effects of chitosan and rice husk powder on thermal hydrolysis-anaerobic digested sludge conditioning: Dewaterability and biogas slurry fertility.

To enhance the dewaterability of anaerobic digested sludge and to make full use of the biogas slurry. This study set up five sludge conditioning methods: polymeric ferric sulfate, polymeric aluminum chloride, cationic polyacrylamide, chitosan, and chitosan combined with rice husk powder. Their effects on the dewaterability of thermal hydrolysis-anaerobic digested sludge, bacterial community, and biogas slurry fertility were studied to find a non-toxic and non-risk dewatering technology for the environment and biogas slurry. Compared with that of the control group, moisture content, normalization capillary suction time, and specific resistance to filtration were reduced by 12.8%, 97.7%, and 82.9%, respectively. Chitosan enlarges the sludge flocs and forms complexes with proteins, disrupting the structure of the extracellular polymeric substances, thereby exposing more hydrophobic groups and reducing the hydrophilicity of the sludge. The subsequent addition of rice husk powder enhances the adsorption of hydrophilic substances and provides a stronger drainage channel for the sludge. In addition, the biogas slurry obtained by this conditioning method used as a fertilizer increased the dry weight and fresh weight of corn seedlings by 59.3% and 91.0%, respectively. And the total chlorophyll content increased by 84.6%. Pearson's correlation analysis showed that chitosan and rice husk meal had no toxic effect on the biogas slurry compared to the other three flocculants. The results showed that the combined treatment of chitosan and rice husk powder resulted in the best dewaterability. Overall, chitosan combined with rice husk powder is a green dewatering technology with great potential for anaerobic digested sludge dewatering and biogas slurry recycling.

Prevention of urinary tract infection using a silver alloy hydrogel-coated catheter in critically ill patients: A single-center prospective randomized controlled study.

Background: A new type of silver alloy hydrogel-coated (SAH) catheter has been shown to prevent bacterial adhesion and colonization by generating a microcurrent, and to block the retrograde infection pathway. However, these have only been confirmed in ordinary patients. This study aims to evaluate the effectiveness of a SAH catheter for preventing urinary tract infections in critically ill patients. Methods: This was a prospective single-center, single-blind, randomized, controlled study. A total of 132 patients requiring indwelling catheterization in the intensive care unit (ICU) of the First Affiliated Hospital of the University of Science and Technology of China between October 2022 and February 2023 and who met the study inclusion/exclusion criteria were randomly divided into two groups. Patients in the SAH catheter group received a SAH catheter, while patients in the conventional catheter group received a conventional siliconized latex Foley catheter. The main outcome measure was the incidence of catheter-associated urinary tract infections (CAUTIs). Secondary outcome indicators included urine positivity for white blood cells and positive urine cultures on 3 days, 7 days, 10 days, and 14 days after catheterization, number of viable bacteria in the catheter biofilm on day 14, pathogenic characteristics of positive urine cultures, length of ICU stay, overall hospital stay, ICU mortality, and 28-day mortality. All the data were compared between the two groups. Results: A total of 68 patients in the conventional catheter group and 64 patients in the SAH catheter group were included in the study. On day 7 after catheter placement, the positivity rate for urinary white blood cells was significantly higher in the conventional catheter group than in the SAH catheter group (33.8% vs. 15.6%, P=0.016). On day 10, the rates of positive urine cultures (27.9% vs. 10.9%, P=0.014) and CAUTIs (22.1% vs. 7.8%, P=0.023) were significantly higher in the conventional catheter group than in the SAH catheter group. On day 14, the numbers of viable bacteria isolated from the catheter tip ([3.21±1.91]×106 colony-forming units [cfu]/mL vs. [7.44±2.22]×104 cfu/mL, P <0.001), balloon segment ([7.30±1.99]×107 cfu/mL vs. [3.48±2.38]×105 cfu/mL, P <0.001), and tail section ([6.41±2.07]×105 cfu/mL vs. [8.50±1.46]×103 cfu/mL, P <0.001) were significantly higher in the conventional catheter group than in the SAH catheter group. The most common bacteria in the urine of patients in both groups were Escherichia coli (n=13) and Pseudomonas aeruginosa (n=6), with only one case of Candida in each group. There were no significant differences between the two groups in terms of ICU hospitalization time, total hospitalization time, ICU mortality, and 28-day mortality. Conclusion: SAH catheters can effectively inhibit the formation of catheter-related bacterial biofilms in critically ill patients and reduce the incidence of CAUTIs, compared with conventional siliconized latex Foley catheters; however, regular replacement of the catheter is still necessary.

Comparison of Thermophilic-Mesophilic and Mesophilic-Thermophilic Two-Phase High-Solid Sludge Anaerobic Digestion at Different Inoculation Proportions: Digestion Performance and Microbial Diversity.

This study investigated the performance of thermophilic-mesophilic (T-M) and mesophilic-thermophilic (M-T) two-phase sludge anaerobic digestion at different inoculation proportions after a change in digestion temperature. After temperature change, the pH, total ammonia nitrogen (TAN), free ammonia nitrogen (FAN), solubility chemical oxygen demand (SCOD), and total alkalinity (TA) levels of two-phase digesters were between thermophilic control digesters and mesophilic control digesters. However, the volatile fatty acid (VFA) levels of two-phase digesters were higher than those of thermophilic or mesophilic control digesters. The bacteria communities of M-T two-phase digesters were more diverse than those of T-M. After a change in digestion temperature, the bacterial community was dominated by Coprothermobacter. After a change of digestion temperature, the relative abundance (RA) of Methanobacterium, Methanosaeta, and Methanospirillum of M-T two-phase digesters was higher than that of T-M two-phase digesters. In comparison, the RA of Methanosarcina of T-M two-phase digesters was higher than that of M-T two-phase digesters. The ultimate methane yields of thermophilic control digesters were greater than those of mesophilic control digesters. Nevertheless, the ultimate methane yield levels of M-T two-phase digesters were greater than those of T-M two-phase digesters. The ultimate methane yields of all two-phase digesters presented an earlier increase and later decrease trend with the increasing inoculation proportion. Optimal methane production condition was achieved when 15% of sludge (T-M15) was inoculated under mesophilic-thermophilic conditions, which promoted 123.6% (based on mesophilic control) or 27.4% (based on thermophilic control). An optimal inoculation proportion (about 15%) balanced the number and activity of methanogens of high-solid sludge anaerobic digestion.

Identification of immune-related lncRNA in sepsis by construction of ceRNA network and integrating bioinformatic analysis.

BACKGROUND: Sepsis is a high mortality disease which seriously threatens human life and health, for which the pathogenetic mechanism still unclear. There is increasing evidence showed that immune and inflammation responses are key players in the development of sepsis pathology. LncRNAs, which act as ceRNAs, have critical roles in various diseases. However, the regulatory roles of ceRNA in the immunopathogenesis of sepsis have not yet been elucidated. RESULTS: In this study, we aimed to identify immune biomarkers associated with sepsis. We first generated a global immune-associated ceRNA (IMCE) network based on data describing interactions pairs of gene-miRNA and miRNA-lncRNA. Afterward, we excavated a dysregulated sepsis immune-associated ceRNA (SPIMC) network from the global IMCE network by means of a multi-step computational approach. Functional enrichment indicated that lncRNAs in SPIMC network have pivotal roles in the immune mechanism underlying sepsis. Subsequently, we identified module and hub genes (CD4 and STAT4) via construction of a sepsis immune-related PPI network. Then, we identified hub genes based on the modular structure of PPI network and generated a ceRNA subnetwork to analyze key lncRNAs associated with sepsis. Finally, 6 lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) that identified as immune biomarkers of sepsis. Moreover, the CIBERSORT algorithm and the infiltration of circulating immune cells types were performed to identify the inflammatory state of sepsis. Correlation analyses between immune cells and sepsis immune biomarkers showed that the LINC00265 was strongly positive correlated with the macrophages M2 (r = 0.77). CONCLUSION: Collectively, these results may suggest that these lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) played important roles in the immune pathogenesis of sepsis and provide potential therapeutic targets for further researches on immune therapy treatment in patients with sepsis.

Phase III study of HR-positive/HER2-negative/lymph node-positive breast cancer non-responsive to primary chemotherapy: a randomized trial.

There are few studies focus on post-neoadjuvant treatment in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-)/lymph node-positive (LN+) breast cancer, a multi-center, open-label, randomized, controlled phase III trial was conducted to evaluate pathological response-guided non-cross-resistant adjuvant chemotherapy in patients with HR+/HER2-/LN+ breast cancer who were non-responsive to primary chemotherapy. Patients received four cycles of non-cross-resistant adjuvant chemotherapy plus endocrine therapy (ET), or ET alone. Forty patients responsive to neoadjuvant chemotherapy and with Miller and Payne G4 or G5 and LN- status were assigned to the observation group. Distant disease-free survival was the primary endpoint. The final intention-to-treat analysis comprised 379 patients. After a median follow-up period of 72.4 months, the 5-year distant disease-free survival was 92% and 90% in the chemotherapy plus ET and ET-alone groups, respectively. Comparatively, the observation group showed a trend towards better distant disease-free survival. For patients non-responsive to neoadjuvant chemotherapy, adjuvant non-cross-resistant chemotherapy did not significantly improve distant disease-free survival compared to ET alone.

Observation Effectiveness of Dose-Dense Neoadjuvant Anthracycline Sequential Weekly Paclitaxel for Triple-Negative Breast Cancer Patients.

INTRODUCTION/BACKGROUND: To investigate the differences in pathological response and survival outcomes between dose-dense and conventional-interval neoadjuvant chemotherapy (NAC) in patients with triple-negative breast cancer (TNBC). PATIENTS AND METHODS: Patients with TNBC who received NAC including epirubicin plus cyclophosphamide followed by weekly paclitaxel were included. A total of 494 patients were divided into either the dose-dense anthracycline (ddEC-wP) group or conventional interval anthracycline (EC-wP) group. RESULTS: The breast pathological complete response (bpCR, ypT0/is) rate was 45.3% (n = 101) in the dose-dense group and 34.3% (n = 93) in the conventionally scheduled group, which was a significant difference (P = .013), and in the 251 pN+ cases, the lymph node pathological complete response (LNpCR, ypN0) rate was 57.9% (n = 62) in the dose-dense group and 43.7% (n = 63) in the conventionally scheduled group, which was a significant difference (P = .026) in the univariate analysis. In the multivariate logistic regression analysis, 3 variables were predictive of bpCR: pathological type, surgical methods and type of chemotherapy, with P values of .012, .001 and .021, respectively. Two variables were predictive of LNpCR: type of chemotherapy and Her-2 expression, with P values of .039 and .020, respectively. After a median follow-up of 54 months, there was no significant difference in survival for disease-free survival (DFS) (hazard ratio [HR], 0.788; 95% confidence interval [CI], 0.508 to 1.223; P = .288), distant disease-free survival (DDFS) (HR, 0. 709; 95% CI, 0.440 to 1.144; P = .159) or overall survival (OS) (HR, 0. 750; 95% CI, 0.420 to 1.338; P = .330) between the 2 groups. CONCLUSION: Our study demonstrated that TNBC achieved a higher bpCR rate and LNpCR rate after dose-dense neoadjuvant chemotherapy than the conventional scheme. The survival benefit of the 2 groups did not reach statistical difference.

CT Radiomics for Predicting Pathological Complete Response of Axillary Lymph Nodes in Breast Cancer After Neoadjuvant Chemotherapy: A Prospective Study.

BACKGROUND: The diagnostic effectiveness of traditional imaging techniques is insufficient to assess the response of lymph nodes (LNs) to neoadjuvant chemotherapy (NAC), especially for pathological complete response (pCR). A radiomics model based on computed tomography (CT) could be helpful. PATIENTS AND METHODS: Prospective consecutive breast cancer patients with positive axillary LNs initially were enrolled, who received NAC prior to surgery. Chest contrast-enhanced thin-slice CT scan was performed both before and after the NAC (recorded as the first and the second CT respectively), and on both of them, the target metastatic axillary LN was identified and demarcated layer by layer. Using pyradiomics-based software that was independently created, radiomics features were retrieved. A pairwise machine learning workflow based on Sklearn (https://scikit-learn.org/) and FeAture Explorer was created to increase diagnostic effectiveness. An effective pairwise auto encoder model was developed by the improvement of data normalization, dimensionality reduction, and features screening scheme as well as the comparison of the prediction effectiveness of the various classifiers. RESULTS: A total of 138 patients were enrolled, and 77 (58.7%) in the overall group achieved pCR of LN after NAC. Nine radiomics features were finally chosen for modeling. The AUCs of the training group, validation group, and test group were 0.944 (0.919-0.965), 0.962 (0.937-0.985), and 1.000 (1.000-1.000), respectively, and the corresponding accuracies were 0.891, 0.912, and 1.000. CONCLUSION: The pCR of axillary LNs in breast cancer following NAC can be precisely predicted using thin-sliced enhanced chest CT-based radiomics.

RNA2Immune: A Database of Experimentally Supported Data Linking Non-coding RNA Regulation to The Immune System.

Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as important regulators of the immune system and are involved in the control of immune cell biology, disease pathogenesis, as well as vaccine responses. A repository of ncRNA-immune associations will facilitate our understanding of ncRNA-dependent mechanisms in the immune system and advance the development of therapeutics and prevention for immune disorders. Here, we describe a comprehensive database, RNA2Immune, which aims to provide a high-quality resource of experimentally supported database linking ncRNA regulatory mechanisms to immune cell function, immune disease, cancer immunology, and vaccines. The current version of RNA2Immune documents 50,433 immune-ncRNA associations in 42 host species, including (1) 6690 ncRNA associations with immune functions involving 31 immune cell types; (2) 38,672 ncRNA associations with 348 immune diseases; (3) 4833 ncRNA associations with cancer immunology; and (4) 238 ncRNA associations with vaccine responses involving 26 vaccine types targeting 22 diseases. RNA2Immune provides a user-friendly interface for browsing, searching, and downloading ncRNA-immune system associations. Collectively, RNA2Immune provides important information about how ncRNAs influence immune cell function, how dysregulation of these ncRNAs leads to pathological consequences (immune diseases and cancers), and how ncRNAs affect immune responses to vaccines. RNA2Immune is available at http://bio-bigdata.hrbmu.edu.cn/rna2immune/home.jsp.

Impact of Sentinel Lymph Node Biopsy on Treatment Decision and Survival in Patients Aged ≥70 Years with Breast Cancer: A Retrospective Study.

Background: Whether sentinel lymph node biopsy should be performed in patients ≥70 years old with early-stage invasive breast cancer is controversial. We examined the effect of sentinel lymph node biopsy on the treatment and outcomes in this population. Materials and Methods: In this retrospective study, patients aged ≥70 years who were treated for invasive breast cancer with sentinel lymph node biopsy followed by mastectomy or lumpectomy between 2010 and 2019 were identified from our database. Patients were compared according to sentinel lymph node status. Outcomes were analyzed using the Kaplan-Meier method and Cox multivariate analysis. Results: Of the 376 patients enrolled in this study, 311 (82.7%) were sentinel lymph node-negative and 65 (17.3%) were sentinel lymph node-positive. The median follow-up duration for all patients was 70 months. Systemic treatment and radiation were similar between sentinel lymph node-negative and -positive groups. Disease-free survival, distant disease-free survival, breast cancer-specific survival, overall survival were not significantly different between groups (88.2% vs 87.6%, 96.7% vs 94.8%, 96.2% vs 93.6%, and 93.5% vs 90.0%, respectively). Sentinel lymph node status, tumor size, chemotherapy, endocrine therapy, and adjuvant radiation were included in Cox multivariate analysis. None of the variables were found to significantly affect disease-free survival, distant disease-free survival, breast cancer-specific survival, and overall survival. Conclusions: Our analysis indicated that sentinel lymph node status may not affect systemic treatment decisions or survival in patients aged ≥70 years with breast cancer.

Anaerobic co-digestion of Chinese cabbage waste and cow manure at mesophilic and thermophilic temperatures: Digestion performance, microbial community, and biogas slurry fertility.

The objective of this study was to investigate the effects of mixing ratios of Chinese cabbage waste (CCW) and cow manure (CM) on methane yields, microbial community, and biogas slurry fertility during anaerobic co-digestion. Batch experiments were conducted at mesophilic and thermophilic temperatures with five different CCW/CM mixing ratios. Methane yields at mesophilic and thermophilic temperatures were 4.2-184.4 mL g-1 Volatile solidsadded (mL g-1 VSadded) and 11.8-321.7 mL g-1 VSadded, respectively. The richness and diversity of bacteria and archaea at mesophilic temperatures were higher than those at thermophilic temperatures. Compared with the unfertilized control, the dry weight of corn seedlings with the follow-up application of mesophilic or thermophilic biogas slurry increased by 12.3 %-73.4 % or 16.8 %-43.3 %, respectively. This study demonstrates that thermophilic temperatures are conducive to increasing methane yields, but mesophilic temperatures are conducive to improving the biogas slurry fertility.

Identification of circulating immune landscape in ischemic stroke based on bioinformatics methods.

Ischemic stroke (IS) is a high-incidence disease that seriously threatens human life and health. Neuroinflammation and immune responses are key players in the pathophysiological processes of IS. However, the underlying immune mechanisms are not fully understood. In this study, we attempted to identify several immune biomarkers associated with IS. We first retrospectively collected validated human IS immune-related genes (IS-IRGs) as seed genes. Afterward, potential IS-IRGs were discovered by applying random walk with restart on the PPI network and the permutation test as a screening strategy. Doing so, the validated and potential sets of IS-IRGs were merged together as an IS-IRG catalog. Two microarray profiles were subsequently used to explore the expression patterns of the IS-IRG catalog, and only IS-IRGs that were differentially expressed between IS patients and controls in both profiles were retained for biomarker selection by the Random Forest rankings. CLEC4D and CD163 were finally identified as immune biomarkers of IS, and a classification model was constructed and verified based on the weights of two biomarkers obtained from the Neural Network algorithm. Furthermore, the CIBERSORT algorithm helped us determine the proportions of circulating immune cells. Correlation analyses between IS immune biomarkers and immune cell proportions demonstrated that CLEC4D was strongly correlated with the proportion of neutrophils (r = 0.72). These results may provide potential targets for further studies on immuno-neuroprotection therapies against reperfusion injury.

Neoadjuvant endocrine therapy for strongly hormone receptor-positive and HER2-negative early breast cancer: results of a prospective multi-center study.

PURPOSE: For estrogen receptor (ER)-positive breast cancer, neoadjuvant endocrine therapy (NET) has been shown to be as effective as neoadjuvant chemotherapy (NACT). We evaluated the prognostic significance of Preoperative Endocrine Prognostic Index (PEPI). METHODS: We conducted a prospective, multi-center, non-randomized, controlled trial that enrolled postmenopausal early-stage strongly ER-positive (≥ 50%) and HER2-negative breast cancer patients. All patients were given 4-month NET before surgery. The primary objective was to investigate the 5-year recurrence-free survival (RFS) in patients who had PEPI 0-1 or pathological complete response (pCR) without chemotherapy. Patients who had PEPI 0-1 or pCR were recommended to receive adjuvant endocrine therapy only and patients had PEPI ≥ 2 may receive adjuvant chemotherapy at the discretion of the treating physician. RESULTS: A total of 410 patients were included and 352 patients constituted the per-protocol population. Overall, 9 patients (2.5%) had pCR (ypT0/is ypN0), 128 patients (36.4%) had PEPI = 0, and 56 patients (15.9%) had PEPI = 1. After a median follow-up of 60 months (4-104 months), patients who had PEPI 0-1 or pCR showed an improved 5-year RFS [99.5% (95% CI 98.5-99.9%) for PEPI 0-1 or pCR group vs. 93.7% (95% CI 89.6-97.8%) for PEPI ≥ 2 group, P = 0.028]. No survival difference was detected between patients received adjuvant chemotherapy vs. no chemotherapy among PEPI ≥ 2 cases. CONCLUSION: PEPI 0-1 or pCR may be used to define a group of ER-positive and HER2-negative postmenopausal early breast cancer patients with low relapse risk for whom adjuvant chemotherapy can be safely withheld. Studies on the identification and alternative treatment options for endocrine-resistant tumors are warranted. CLINICAL TRIAL REGISTRATION: NCT01613560.

LncRNA LINC00680 Acts as a Competing Endogenous RNA and Is Associated With the Severity of Myasthennia Gravis.

Background and Purpose: Myasthenia gravis (MG) is a T cell-dependent antibody-mediated autoimmune disorder that can seriously affect patients' quality of life. However, few studies have focused on the severity of MG. Moreover, existing therapeutic efforts, including those targeting biomarkers for MG, remain unsatisfactory. Therefore, it is vital that we investigate the pathogenesis of MG and identify new biomarkers that can not only evaluate the severity of the disease but also serve as potential therapeutic targets. Long noncoding RNA LINC00680 has been found to be associated with the progression of a variety of diseases as a competing endogenous RNA (ceRNA). However, the specific role of LINC00680 in MG has yet to be clarified. Here, we aimed to investigate the association between LINC00680 and the severity of MG. Methods: Bioinformatics tools, quantitative real-time PCR, Western blotting, and luciferase assays were selected to investigate key signaling pathways and RNA expression in patients with MG. The Quantitative MG Score scale and the MG Composite scale were used to evaluate the severity of MG in the included patients. Cell viability assays and flow cytometry analysis were selected to analyze cell proliferation and apoptosis. Results: Compared with control subjects, the expression levels of LINC00680 and mitogen-activated protein kinase 1 (MAPK1) in peripheral blood mononuclear cells of patients with MG were both upregulated; the levels of miR-320a were downregulated. A positive correlation was detected between LINC00680 expression and the severity of MG. Luciferase reporter assays identified that LINC00680 acts as a target for miR-320a. The in vitro analysis confirmed that LINC00680 regulates the expression of MAPK1 by sponging miR-320a. Finally, the functional analysis indicated that LINC00680 promoted Jurkat cell proliferation and inhibited cellular apoptosis by sponging miR-320a. Conclusion: LINC00680 may be associated with the severity of MG as a ceRNA by sponging miR-320a to upregulate MAPK1. These findings suggest that LINC00680 may represent a potential biomarker which evaluates the severity of MG and may serve as a therapeutic target.

Risk of ipsilateral breast tumor recurrence and contralateral breast cancer in patients with and without TP53 variant in a large series of breast cancer patients.

BACKGROUND: The association between breast cancer patients with a TP53 pathogenic variant and risk of local recurrence and contralateral breast cancer remains largely unknown. METHODS: The study population of 11093 patients was derived from two cohorts at the Breast Center of Peking University Cancer Hospital in China from November 2003, to March 2018. TP53 germline variants were determined for all patients. RESULTS: In the study, forty-one (0.37%) carried a TP53 germline pathogenic variant, and 11052 were non-carriers (99.63%). Nineteen TP53 carriers (46.3%) and 4173 non-carriers (37.8%) were treated with breast-conserving therapy (BCT), while the remaining were treated with mastectomy. After a median follow-up of 6.7 years, the rate of ipsilateral breast tumor recurrence (IBTR) in TP53 carriers was significantly higher than that in non-carriers when treated with BCT (21.1% vs 3.8%, P = 0.006). No difference in the rate of IBTR was found between TP53 carriers and non-carriers when treated with mastectomy (0.0% vs 2.6%, P = 1.0). Furthermore, the rate of IBTR in TP53 carriers treated with BCT was significantly higher than that in those treated with mastectomy (21.1% vs 0.0%, P = 0.038). The 10-year cumulative risk of contralateral breast cancer in TP53 carriers was significantly higher than that in non-carriers (17.9% vs 3.6%, hazard ratio (HR) = 7.0, 95% CI: 3.3-14.9, P < 0.001). CONCLUSIONS: Patients with TP53 variants have a high risk of IBTR when treated with BCT, and exhibit a very high risk of contralateral breast cancer. TP53 carriers may not be suitable for BCT and prophylactic contralateral mastectomy might be considered.

Dissecting and analyzing the Subclonal Mutations Associated with Poor Prognosis in Diffuse Glioma.

The prognostic and therapeutic implications in diffuse gliomas are still challenging. In this study, we first performed an integrative framework to infer the clonal status of mutations in glioblastomas (GBMs) and low-grade gliomas (LGGs) by using exome sequencing data from TCGA and observed both clonal and subclonal mutations for most mutant genes. Based on the clonal status of a given gene, we systematically investigated its prognostic value in GBM and LGG, respectively. Focusing on the subclonal mutations, our results showed that they were more likely to contribute to the poor prognosis, which could be hardly figured out without considering clonal status. These risk subclonal mutations were associated with some specific genomic features, such as genomic instability and intratumor heterogeneity, and their accumulation could enhance the prognostic value. By analyzing the regulatory mechanisms underlying the risk subclonal mutations, we found that the subclonal mutations of AHNAK and AHNAK2 in GBM and those of NF1 and PTEN in LGG could influence some important molecules and functions associated with glioma progression. Furthermore, we dissected the role of risk subclonal mutations in tumor evolution and found that advanced subclonal mutations showed poorer overall survival. Our study revealed the importance of clonal status in prognosis analysis, highlighting the role of the subclonal mutation in glioma prognosis.

LncRNA OIP5-AS1 modulates the proliferation and apoptosis of Jurkat cells by sponging miR-181c-5p to regulate IL-7 expression in myasthenia gravis.

Background: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease. In recent years, accumulating evidence has indicated that long non-coding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs), contributing to the progression of various autoimmune diseases. Nevertheless, the regulatory roles of ceRNAs in MG pathogenesis remain unclear. In this study, we aimed to elucidate the role of lncRNA OIP5-AS1 as a ceRNA associated with MG progression. Methods: Real-time PCR was used to detect OIP5-AS1 levels in peripheral blood mononuclear cells (PBMCs) from patients with MG. Luciferase reporter assays were performed to validate the relationship between OIP5-AS1 and miR-181c-5p. CCK-8 and flow cytometry were performed to test the proliferation and apoptotic abilities of OIP5-AS1 in Jurkat cells. Furthermore, real-time PCR and Western blot assays were performed to explore the interactions between OIP5-AS1, miR-181c-5p, and IL-7. Results: The expression of OIP5-AS1 was up-regulated in patients with MG. Luciferase reporter assay indicated that OIP5-AS1 targeted the miR-181c-5p. Functional assays showed that OIP5-AS1 suppressed Jurkat cell apoptosis and promoted cell proliferation by sponging miR-181c-5p. Mechanistically, knockdown of OIP5-AS1 inhibited IL-7 expression at both the mRNA and protein levels in Jurkat cells, whereas the miR-181c-5p inhibitor blocked the reduction of IL-7 expression induced by OIP5-AS1 suppression. Conclusions: We confirmed that OIP5-AS1 serves as an endogenous sponge for miR-181c-5p to regulate the expression of IL-7. Our findings provide novel insights into MG processes and suggests potential therapeutic targets for patients with MG.