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.

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.

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.

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.

MicroRNAs and nervous system diseases: network insights and computational challenges.

The nervous system is one of the most complex biological systems, and nervous system disease (NSD) is a major cause of disability and mortality. Extensive evidence indicates that numerous dysregulated microRNAs (miRNAs) are involved in a broad spectrum of NSDs. A comprehensive review of miRNA-mediated regulatory will facilitate our understanding of miRNA dysregulation mechanisms in NSDs. In this work, we summarized currently available databases on miRNAs and NSDs, star NSD miRNAs, NSD spectrum width, miRNA spectrum width and the distribution of miRNAs in NSD sub-categories by reviewing approximately 1000 studies. In addition, we characterized miRNA-miRNA and NSD-NSD interactions from a network perspective based on miRNA-NSD benchmarking data sets. Furthermore, we summarized the regulatory principles of miRNAs in NSDs, including miRNA synergistic regulation in NSDs, miRNA modules and NSD modules. We also discussed computational challenges for identifying novel miRNAs in NSDs. Elucidating the roles of miRNAs in NSDs from a network perspective would not only improve our understanding of the precise mechanism underlying these complex diseases, but also provide novel insight into the development, diagnosis and treatment of NSDs.

Effect of Local Versus General Anesthesia in Breast-Conserving Surgery on Cancer Recurrence and Cost.

BACKGROUND: The association between the type of anesthesia used and the recurrence of cancer remains controversial. This study aimed to compare the effects of local vs general anesthesia on recurrence-free survival and cost after breast-conserving surgery. MATERIALS AND METHODS: We reviewed the data of 2778 patients who underwent breast-conserving surgery followed by radiation at our center between 1999 and 2014. We analyzed the data of 994 patients with hormone receptor-positive and Her2-negative tumors who underwent breast-conserving surgery without axillary lymph node dissection under local or general anesthesia. Patients were grouped according to whether local or general anesthesia was used for the surgery. RESULTS: Of the 994 patients enrolled in this study, 367 received local anesthesia and 627 patients received general anesthesia. The median follow-up duration for all patients was 93 months. The Kaplan-Meier survival curves did not reveal significant differences between the recurrence-free survival of the two groups, with 5-year recurrence-free survival rates of 96.3% (95% CI, 94.3-98.3%) in the local anesthesia group and 97.3% (95% CI, 95.9-98.7%) in the general anesthesia group. The total cost of hospitalization in the local anesthesia group was significantly lower than that in the general anesthesia group (P <.001). The difference in the cost between the two groups remained significant, irrespective of the type of hospitalization, after excluding 165 patients receiving chemotherapy during their hospitalization. CONCLUSIONS: Our analysis indicated no association between the type of anesthesia used during breast-conserving surgery and the long-term prognosis of breast cancer. However, breast-conserving surgery under local anesthesia may be a less expensive option than that under general anesthesia.

Impact of the addition of carboplatin to anthracycline-taxane-based neoadjuvant chemotherapy on survival in BRCA1/2-mutated triple-negative breast cancer.

Whether adding carboplatin to standard neoadjuvant chemotherapy improves survival in BRCA1/2-mutated triple-negative breast cancer (TNBC) is unknown. In this retrospective study, we aimed to explore the efficacy of anthracycline-taxane (A-T)-based or anthracycline-taxane/carboplatin (A-TP)-based neoadjuvant chemotherapy in BRCA1/2-mutated TNBC. A total of 1585 operable primary breast cancer patients were treated with either neoadjuvant A-T (n = 886) or A-TP regimen (n = 699). BRCA1 and BRCA2 germline mutations were determined in all subjects. Pathological complete response (pCR), recurrence-free survival (RFS), distant recurrence-free survival (DRFS) and overall survival (OS) were estimated. Of the entire cohort, 102 patients (6.4%) carried a pathogenic BRCA1/2 germline mutation. After a median follow-up of 81 months, no significant differences in survival between the A-T and A-TP arms were found in the entire cohort. However, among 288 TNBC patients, BRCA1/2 mutation carriers had significantly better survival when treated with the A-TP regimen than with the A-T regimen (5-year RFS: 82.6% vs 47.9%; P = .024; 5-year DRFS: 88.5% vs 46.9%; P = .010; 5-year OS: 88.2% vs 49.9%; P = .036). Multivariate analyses revealed that the A-TP regimen was a significantly favourable factor for RFS and DRFS and showed a trend towards better OS when compared with the A-T regimen in BRCA1/2-mutated TNBC (RFS: adjusted hazard ratio [HR], 0.24; 95% confidence interval [CI], 0.06-0.91, P = .035; DRFS: HR, 0.17; 95% CI, 0.03-0.80; P = .025; OS: HR, 0.29; 95% CI, 0.06-1.49; P = .14). Our study suggested that BRCA1/2-mutated TNBC patients gain a survival benefit when carboplatin is added to standard A-T-based neoadjuvant chemotherapy.

Identification of the regulatory role of lncRNA HCG18 in myasthenia gravis by integrated bioinformatics and experimental analyses.

BACKGROUND: Long non-coding RNAs (lncRNAs), functioning as competing endogenous RNAs (ceRNAs), have been reported to play important roles in the pathogenesis of autoimmune diseases. However, little is known about the regulatory roles of lncRNAs underlying the mechanism of myasthenia gravis (MG). The aim of the present study was to explore the roles of lncRNAs as ceRNAs associated with the progression of MG. METHODS: MG risk genes and miRNAs were obtained from public databases. Protein-protein interaction (PPI) network analysis and module analysis were performed. A lncRNA-mediated module-associated ceRNA (LMMAC) network, which integrated risk genes in modules, risk miRNAs and predicted lncRNAs, was constructed to systematically explore the regulatory roles of lncRNAs in MG. Through performing random walk with restart on the network, HCG18/miR-145-5p/CD28 ceRNA axis was found to play important roles in MG, potentially. The expression of HCG18 in MG patients was detected using RT-PCR. The effects of HCG18 knockdown on cell proliferation and apoptosis were determined by CCK-8 assay and flow cytometry. The interactions among HCG18, miR-145-5p and CD28 were explored by luciferase assay, RT-PCR and western blot assay. RESULTS: Based on PPI network, we identified 9 modules. Functional enrichment analyses revealed these modules were enriched in immune-related signaling pathways. We then constructed LMMAC network, containing 25 genes, 50 miRNAs, and 64 lncRNAs. Through bioinformatics algorithm, we found lncRNA HCG18 as a ceRNA, might play important roles in MG. Further experiments indicated that HCG18 was overexpressed in MG patients and was a target of miR-145-5p. Functional assays illustrated that HCG18 suppressed Jurkat cell apoptosis and promoted cell proliferation. Mechanistically, knockdown of HCG18 inhibited the CD28 mRNA and protein expression levels in Jurkat cells, while miR-145-5p inhibitor blocked the reduction of CD28 expression induced by HCG18 suppression. CONCLUSION: We have reported a novel HCG18/miR-145-5p/CD28 ceRNA axis in MG. Our findings will contribute to a deeper understanding of the molecular mechanism of and provide a novel potential therapeutic target for MG.

Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers in a large cohort of unselected Chinese breast cancer patients.

To estimate the cumulative risk of contralateral breast cancer (CBC) in BRCA1/2 carriers in a large cohort of unselected Chinese breast cancer patients. Our study comprised 9,401 unselected Chinese breast cancer patients and BRCA1/2 germline mutations were determined in all patients. After a median follow-up of 5.7 years, 181 patients developed CBC in this cohort. Compared to noncarriers, BRCA1 and BRCA2 carriers had a 4.52-fold (95% CI, 2.63-7.76) and 5.54-fold (95% CI, 3.51-8.74) increased risk of CBC, respectively. The 10-year cumulative risk of CBC was 15.5% (95% CI, 9.9-24.2) for BRCA1 carriers, 17.5% (95% CI, 10.9-28.0) for BRCA2 carriers and 3.2% (95% CI, 2.5-4.1) for noncarriers. Younger age at first breast cancer diagnosis was significantly associated with an increased 10-year risk of CBC for BRCA1 carriers (≤40 years vs. >40 years: 21.5% vs. 11.9%, unadjusted hazard ratio [HR] = 2.51, 95% CI, 1.03-6.15, p = 0.044), but not for BRCA2 carriers and noncarriers. The 10-year cumulative CBC risk was significantly higher in both BRCA1 and BRCA2 carriers who had a family history of breast cancer than in those who did not (BRCA1: 27.5% vs. 9.4%, adjusted HR = 2.64, 95% CI, 1.01-6.97, p = 0.049; BRCA2: 27.1% vs. 12.8%, adjusted HR = 2.29, 95% CI, 1.04-5.06, p = 0.040). In conclusion, the risk of CBC was a substantial high in BRCA1/2 carriers in unselected Chinese breast cancer patients, and CBC risk is much more remarkable in both BRCA1 and BRCA2 carriers who had a family history of breast cancer. Younger age at first breast cancer diagnosis also enhanced CBC risk in BRCA1 carriers.

BRCA1 c.5470_5477del, a founder mutation in Chinese Han breast cancer patients.

The spectrum and frequency of BRCA1/2 pathogenic variants may be ethnicity-specific. Whether high-frequency founder mutations are present in Chinese women remains largely unknown. In the current study, germline pathogenic variants in the BRCA1/2 genes were determined in 9,505 unselected Chinese Han breast cancer (BC) patients by next-generation and/ or Sanger sequencing. Four hundred and seventy-one (5.0%) BC patients carried BRCA1/2 pathogenic variants in this cohort. A total of 25 recurrent pathogenic variants (at least found in four unrelated patients) were identified in this cohort (8 BRCA1 and 17 BRCA2 recurrent pathogenic variants), 161 patients carried one of these recurrent pathogenic variants in this cohort of 9,505 patients. All of these 25 recurrent pathogenic variants were further explored whether they had founder effect through haplotype analysis. The most common pathogenic variant, BRCA1 c.5470_5477del, was found in 30 BC patients from 29 unrelated families. Twenty-seven of these 29 unrelated patients who carried this BRCA1 c.5470_5477del mutation shared an identical haplotype, indicating that BRCA1 c.5470_5477del was a founder mutation in the Chinese Han population. Furthermore, BRCA1 c.5470_5477del mutation carriers had a significantly worse survival than noncarriers (disease-free survival, p = 0.049; overall survival, p = 0.029). Taken together, our data suggested that BRCA1 c.5470_5477del is a founder mutation in the Chinese Han population and BRCA1 c.5470_5477del mutation carriers have a poor survival.

Prevalence and clinical impact of TP53 germline mutations in Chinese women with breast cancer.

The prevalence and clinical relevance of TP53 germline mutations in a large unselected breast cancer series are largely unknown. Here, we determined TP53 germline mutations in a large cohort of 10,053 unselected breast cancer patients through multigene panel-based next-generation and/or Sanger sequencing assays. We found that 0.5% of patients (50 cases) carried a pathogenic TP53 germline mutation in this large series of 10,053 unselected breast cancer patients, and the prevalence of TP53 germline mutation was 3.8% in very early onset breast cancer (age ≤30 years) in this large cohort. TP53 mutation carriers were significantly more likely to have early onset cancer (p < 0.001) and bilateral breast cancer (p = 0.03), they and were significantly more likely to respond to carboplatin-based neoadjuvant chemotherapy compared to anthracycline- or taxane-based regimen in terms of pathologic complete response (50% vs. 0%, p = 0.006). At the median follow-up of 54 months, TP53 mutation was an independent unfavorable factor for recurrence-free survival (RFS), distant recurrence-free survival (DRFS), and overall survival (OS) (RFS, adjusted hazard ratio [HR]: 2.24, 95% confidence interval [CI]: 1.15-4.33, p = 0.02; DRFS, adjusted HR: 2.73, 95% CI: 1.41-5.30, p = 0.003; OS, adjusted HR: 4.60, 95% CI: 2.26-9.41, p < 0.001) in multivariate analyses. Our study suggested that TP53 germline mutations occur more frequently in very early onset unselected breast cancer patients; and TP53 germline mutation carriers have a very poor survival and may benefit from carboplatin-based neoadjuvant chemotherapy in unselected breast cancer patients.

Comparisons of breast conserving therapy versus mastectomy in young and old women with early-stage breast cancer: long-term results using propensity score adjustment method.

PURPOSE: This study aimed to compare the effect of BCT versus mastectomy on the recurrence and survival of different-aged patients, and to investigate whether effects of BCT versus mastectomy on survival of young patients were consistent with those of old patients. METHODS: Data on women with primary invasive breast cancer between 2007 and 2011 were extracted from the institutional database of Breast Center. Disparities in hormone receptor, tumor size, lymph node status, and Her-2 status between BCT and mastectomy groups were adjusted using the propensity score (PS) adjustment method. Patients were divided by age into two groups (≤ 40 years and > 40 years). We assessed proportions of local recurrence (LR), distant disease-free survival (DDFS), disease-free survival (DFS), and breast cancer-specific survival (BCSS) in different-aged groups; this assessment was further stratified by surgical treatment. RESULTS: A total of 2964 patients were included; 565 (19%) were aged ≤ 40 years. In the entire cohort, hazard ratios (HR) of BCT versus mastectomy for DDFS and DFS were 0.56 (P = 0.029) and 0.55 (P = 0.008), respectively. After PS adjustment, there was no significant difference between BCT and mastectomy in LR, DDFS, DFS and BCSS in the young age group. In the old age group, women who underwent BCT exhibited improved DDFS (HR 0.57, 95% CI 0.39-0.84, P = 0.004). CONCLUSIONS: BCT did not significantly affect survival outcomes of young patients with breast cancer. Superior survival of BCT compared to mastectomy was observed only in old patients.

Spectrum and clinical relevance of PALB2 germline mutations in 7657 Chinese BRCA1/2-negative breast cancer patients.

PURPOSE: To investigate the prevalence and clinical relevance of PALB2 germline mutations in BRCA1/2-negative breast cancer patients. METHODS: The exons and intron-exon boundaries of the PALB2 gene were sequenced by multigene panel testing in a cohort of 7657 Chinese BRCA1/2-negative breast cancer patients. RESULTS: Of the 7657 patients, 54 (0.71%) carried pathogenic PALB2 germline mutations, all of which were nonsense or frameshift mutations leading to a truncated protein. The 54 patients carried 42 distinct pathogenic mutations, of which 17 (40.5%) were novel and 8 were recurrent mutations. Compared with non-carriers, PALB2 pathogenic mutation carriers developed breast cancer at a younger age (47.52 years vs. 51.35 years, p = 0.016) and were more likely to have triple-negative (24.1% vs. 13.4%, p = 0.022) or HER2 negative (87.0% vs. 74.2%, p = 0.031) breast cancer and large breast tumors (> 2 cm) at diagnosis (72.2% vs. 57.0%, p = 0.024). PALB2 mutation carriers were also more likely to have family histories of breast and/or ovarian cancer (27.8% vs. 8.4%, p < 0.001) and any types of cancer (57.4% vs. 31.6%, p < 0.001) when compared with non-carriers. CONCLUSIONS: PALB2 germline mutations are present at 0.71% in Chinese BRCA1/2-negative breast cancer patients and are more frequent in patients with triple-negative breast cancer and family histories of breast and/or ovarian cancer.

Blue light therapy to treat candida vaginitis with comparisons of three wavelengths: an in vitro study.

Anti-fungal blue light (ABL) therapies have been widely studied to treat various microbial infections in the literature. The blue light with wavelengths ranging from 400 to 470 nm has been reported to be effective to inhibit various kinds of bacteria and fungi. The existing studies usually report the viability rates of the pathogens under the irradiation of the blue light with different dosage parameters. However, to the best of our knowledge, there is still no work especially focusing on studying the effect of ABL therapies on treating candida vaginitis, where it is important to study the viability of both the Candida albicans (C. albicans) and the human vaginal epithelial cells. It is the purpose of this work to conduct ABL experiments on both of these two cells, analyze the effects, and determine the best ABL wavelength out of three candidates, i.e., 405-nm, 415-nm, and 450-nm wavelength. The viability rates of the C. albicans and the human vaginal epithelial cells irradiated by the three blue LED light sources were measured, whose irradiance (power density) were all set to 50 mW/cm2. The dynamic viability models of the C. albicans and the epithelial cells were built based on the experimental data. Moreover, in this work, we also built a functional relationship between the viability of these two types of cells, by which we further compared the effects of the blue light irradiation on both the C. albicans and vaginal epithelial cells. The experimental data showed that when an approximately 80% inhibiting rate of the C. albicans was achieved, the survival rates of the epithelial cells were 0.6700, 0.7748, and 0.6027, respectively for the treatment by the 405-nm, 415-nm, and 450-nm wavelength light. On the other hand, by simulating the functional relationship between the viability of the two types of cells, the survival rates of the epithelial cells became 0.5783, 0.6898, and 0.1918 respectively using the 405-nm, 415-nm and 450-nm wavelength light, when the C. albicans was completely inhibited. Therefore, both the experimental data and the model simulation results have demonstrated that the 415-nm light has a more effective anti-fungal result with less damage to the epithelial cells than the 405-nm and 450-nm light.

The influence of different sludge concentrations on its dewaterability during bioleaching.

Bioleaching, a technologically and economically feasible technology, is considered as the high efficiency method to improve dewaterability in sewage sludge. The objective of this study was to investigate the effect of different sludge concentrations on bioleaching dewaterability and understand the mechanism of the effect of bioleaching on sludge dewaterability. Variation in pH, oxidation-reduction potential (ORP), capillary suction time (CST), specific resistance to filtration (SRF) and different fractions of extracellular polymeric substances (EPS) including slime EPS (S-EPS), loosely bound EPS (LB-EPS), and tightly bound EPS (TB-EPS) were determined. Different sludge concentrations (5, 10, 15, 20 and 30 g·L-1) were selected to investigate during bioleaching. Results indicated that sludge buffering capacity significantly inhibited bioleaching efficiency as sludge concentrations increased. Optimum enhancements in sludge dewaterability were observed during the 10 g·L-1 sludge concentration treatment, and reached a maximum when the pH was 2.11. The variation of different fractions of EPS revealed that the ratio of S-EPS/TB-EPS significantly affected sludge dewaterability. Principal component analysis and Pearson's correlation analysis both provided evidence that the higher TB-EPS followed by a very large reduction was positively correlated with sludge dewaterability. However, the increase of protein and DNA in S-EPS content was negatively correlated with sludge dewaterability.

The long noncoding RNA MALAT-1 functions as a competing endogenous RNA to regulate MSL2 expression by sponging miR-338-3p in myasthenia gravis.

Myasthenia gravis (MG) is a cell-dependent autoimmune disease commonly associated with thymic pathology. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) has been associated with gene regulation and alternative splicing. It has shown relationship with proliferation, apoptosis, migration, and invasion. In this study, we found that MALAT-1 expression was downregulated in MG. The level of the miR-338-3p was increased in peripheral blood mononuclear cells from MG patients compared with those from control subjects. MALAT-1 competed for binding to miR-338-3p with male-specific lethal 2 (MSL2) in luciferase reporter assays. We confirmed the MALAT-1-miR-338-3p-MSL2 interaction network in MG in vitro. Thus, MALAT-1 directly induced MSL2 expression in MG by acting as a competing endogenous RNA for miR-338-3p, suggesting that it may serve as a therapeutic target for MG treatment.

Germline mutation in DNA-repair genes is associated with poor survival in BRCA1/2-negative breast cancer patients.

BRCA1/2 genes are the most frequently germline mutated DNA-repair genes, and the survival of BRCA1/2 carriers has been extensively explored in breast cancer. However, the prevalence of germline mutations in non-BRCA1/2 DNA-repair genes and the survival of carriers are largely unknown in a large cohort of unselected breast cancer patients. Germline mutations in 16 DNA-repair genes were determined using a multigene panel in 7657 BRCA1/2-negative breast cancer patients who were unselected for family history of cancer or age at diagnosis. Among the 7657 BRCA1/2-negative breast cancer patients, 257 (3.4%) carried at least 1 pathogenic germline mutation in the 16 DNA-repair genes. The prevalence of DNA-repair gene mutations was significantly higher in familial breast cancers (5.2%, P = 0.002) and early-onset breast cancers (diagnosed at and before the age of 40) (4.5%, P = 0.003) than that of sporadic breast cancers (2.9%) (diagnosed above age of 40), respectively. The DNA-repair gene mutation carriers were significantly more likely to have a larger tumor (P = 0.04) and axillary lymph node metastasis (P = 0.03). Moreover, DNA-repair gene mutation was an independent unfavorable factor for recurrence-free survival (adjusted hazard ratio [HR] = 1.38, 95% CI: 1.00-1.91, P = 0.05) and disease-specific survival (adjusted HR=1.63, 95% CI: 1.04-2.57, P = 0.03) in this cohort. Overall, 3.4% of BRCA1/2-negative breast cancer patients carried germline mutations in the 16 DNA-repair genes, and the DNA-repair gene mutation carriers exhibited an aggressive phenotype and had poor survival compared with noncarriers.

Risk of ipsilateral breast tumor recurrence in primary invasive breast cancer following breast-conserving surgery with BRCA1 and BRCA2 mutation in China.

PURPOSE: BRCA1/2 germline mutations are associated with a high risk of breast cancer, which may preclude mutation carriers from breast-conserving surgery (BCS). This study retrospectively examined whether mutation status influenced the rate of ipsilateral breast tumor recurrence (IBTR) after BCS  in Chinese women. METHODS: Patients who underwent BCS were enrolled in carriers group and non-carriers group according to their BRCA1/2 mutation status in the study. The correlations were analyzed between IBTR incidence and BRCA1/2 mutation. The IBTR cases were further separated into new primary tumor (NP) and true local recurrences (TR). The risk factors of NP were studied in multivariate analysis. RESULTS: 1947 consecutive Chinese women with primary invasive breast cancer were selected. 103 patients were identified as BRCA1/2 mutation carriers and 1844 were non-carriers. BRCA1/2 mutation carriers were younger (P < 0.001) with more often negative HER-2 expression (P = 0.01) and tumor size over 2 cm (P = 0.04) than non-carriers. The median follow-up for all patients was 80 months. The rate of IBTR was 3.9% in mutated carriers and 2.0% in non-carriers, respectively (P = 0.16). In IBTR cases, NP incidence was 3.9% in carrier group and 0.6% in non-carrier group, respectively (P < 0.01). After adjustment of all clinical-pathological factors, BRCA1/2 mutation was the only statistical risk factor of NP incidence (HR = 6.29, P = 0.002), while positive lymph node was nearly statistically significant (HR = 2.70, P = 0.06). CONCLUSIONS: BCS may be a rational option for Chinese BRCA1/2 mutation carriers. High NP incidence in mutation carriers should be paid close attention in the future.

Prevalence and characterization of ATM germline mutations in Chinese BRCA1/2-negative breast cancer patients.

PURPOSE: The ataxia telangiectasia-mutated (ATM) gene is a moderate susceptibility gene for breast cancer. However, little is known about the breast cancer phenotypes associated with ATM mutation. We therefore investigated the spectrum and clinical characteristics of ATM germline mutations in Chinese breast cancer patients. METHODS: A multi-gene panel was performed to screen for ATM germline mutations in 7657 BRCA1/2-negative breast cancer patients. All deleterious mutations were validated by independent polymerase chain reaction (PCR)-Sanger sequencing. RESULTS: A total of 31 pathogenic mutations in the ATM gene across 30 carriers were identified, and the ATM mutation rate was 0.4% (30/7,657) in this cohort. The majority of the mutations (90.3%, 28/31) were nonsense or frameshift mutations. Of the total ATM mutations, 61.3% (19/31) were novel mutations and 13 recurrent mutations were found. ATM mutations carriers were significantly more likely to have a family history of breast and/or ovarian cancer (26.7% in carriers vs. 8.6% in non-carriers, p < 0.001), as well as a family history of any cancer (60.0% in carriers vs. 31.5% in non-carriers, p = 0.001). In addition, ATM mutations carriers were significantly more likely to have oestrogen receptor (ER)-positive (p = 0.011), progesterone receptor (PR)-positive (p = 0.040), and lymph node-positive breast cancer (p = 0.034). CONCLUSIONS: The prevalence of the ATM mutation is approximately 0.4% in Chinese BRCA1/2-negative breast cancer. ATM mutation carriers are significantly more likely to have a family history of cancer and to develop ER- and/or PR-positive breast cancer or lymph node-positive breast cancer.

Associations of BAFF rs2893321 polymorphisms with myasthenia gravis susceptibility.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune diseases characterized by fatigue and weakness of skeletal muscles. B-lymphocyte-activating factor (BAFF), an essential factor for B cell differentiation and development, is important in the progression of MG. The current study aimed to investigate the association between single nucleotide polymorphism rs2893321 in BAFF with MG susceptibility in Chinese Han population. METHODS: One hundred forty-nine patients with MG and 148 healthy controls were recruited. Using improved multiple ligase detection reaction technology, the polymorphisms of rs2893321 between groups and among MG subgroups have been compared. RESULTS: A significant differences between the MG group and the healthy control group was observed. Additionally, rs2893321 was found to be associated with gender and age in patients with MG. CONCLUSION: Genetic variations of rs2893321 in BAFF might be associated with susceptibility to MG in the Chinese Han population.