Aerobic Denitrification Enhanced by Immobilized Slow-Released Iron/Activated Carbon Aquagel Treatment of Low C/N Micropolluted Water: Denitrification Performance, Denitrifying Bacterial Community Co-occurrence, and Implications.

The key limiting factors in the treatment of low C/N micropolluted water bodies are deficient essential electron donors for nitrogen removal processes. An iron/activated carbon aquagel (IACA) was synthesized as a slowly released inorganic electron donor to enhance aerobic denitrification performance in low C/N micropolluted water treatment. The denitrification efficiency in IACA reactors was enhanced by more than 56.72% and the highest of 94.12% was accomplished compared with those of the control reactors. Moreover, the CODMn removal efficiency improved by more than 34.32% in IACA reactors. The Illumina MiSeq sequencing consequence explained that the denitrifying bacteria with facultative denitrification, iron oxidation, and iron reduction function were located in the dominant species niches in the IACA reactors (e.g., Pseudomonas, Leptothrix, and Comamonas). The diversity and richness of the denitrifying bacterial communities were enhanced in the IACA reactors. Network analysis indicated that aerobic denitrifying bacterial consortia in IACA reactors presented a more complicated co-occurrence structure. The IACA reactors presented the potential for long-term denitrification operation. This study affords a pathway to utilize IACA, promoting aerobic denitrification during low C/N micropolluted water body treatment.

Temporal patterns of algae in different urban lakes and their correlations with environmental variables in Xi'an, China.

Urban lakes were critical in aquatic ecology environments, but how environmental factors affected the distribution and change characteristics of algal communities in urban lakes of Xi'an city was not clearly. Here, we investigated the algal community structure of six urban lakes in Xi'an and evaluated the effects of water quality parameters on algae. The results indicated that the significant differences on physicochemical parameters existed in different urban lakes. The maximum concentration of total phosphorus in urban lakes was (0.18 ± 0.01) mg/L and there was a phenomenon of phosphorus limitation. In addition, 51 genera of algae were identified and Chlorella sp. was the dominant algal species, which was affiliated with Chlorophyta. Network analysis elucidated that each lake had a unique algal community network and the positive correlation was dominant in the interaction between algae species, illustrating that mature microbial communities existed or occupied similar niches. Redundancy analysis illustrated that environmental factors explained 47.35% variance of algal species-water quality correlation collectively, indicating that water quality conditions had a significant influence on the temporal variations of algae. Structural equation model further verified that algal community structure was directly or indirectly regulated by different water quality conditions. Our study shows that temporal patterns of algal communities can reveal the dynamics and interactions of different urban ecosystem types, providing a theoretical basis for assessing eutrophication levels and for water quality management.

Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE): a multicentre, single-arm, two-cohort, phase 2 trial.

BACKGROUND: Patients with HER2-positive metastatic breast cancer have a high risk of developing brain metastases. Efficacious treatment options are scarce. We investigated the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases. METHODS: We did a multicentre, single-arm, two-cohort, phase 2 trial in eight tertiary hospitals in China. Patients aged 18 years or older who had radiotherapy-naive HER2-positive brain metastases (cohort A) or progressive disease after radiotherapy (cohort B), with an Eastern Cooperative Oncology Group performance status of 0-2, received pyrotinib 400 mg orally once daily, and capecitabine 1000 mg/m2 orally twice daily for 14 days, followed by 7 days off every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was confirmed intracranial objective response rate by investigator assessment according to the Response Evaluation Criteria In Solid Tumours (version 1.1). Activity and safety were analysed in patients with at least one dose of study drug. The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov, NCT03691051. FINDINGS: Between Jan 29, 2019, and July 10, 2020, we enrolled 78 women: 51 (86%) of 59 patients in cohort A and 18 (95%) of 19 patients in cohort B had previous exposure to trastuzumab. Median follow-up duration was 15·7 months (IQR 9·7-19·0). The intracranial objective response rate was 74·6% (95% CI 61·6-85·0; 44 of 59 patients) in cohort A and 42·1% (20·3-66·5; eight of 19 patients) in cohort B. The most common grade 3 or worse treatment-emergent adverse event was diarrhoea (14 [24%] in cohort A and four [21%] in cohort B). Two (3%) patients in cohort A and three (16%) in cohort B had treatment-related serious adverse events. No treatment-related deaths occurred. INTERPRETATION: To our knowledge, this is the first prospective study showing the activity and safety of pyrotinib plus capecitabine in patients with HER2-positive breast cancer and brain metastases, especially in radiotherapy-naive population. This combination deserves further validation in a randomised, controlled trial. FUNDING: National Cancer Centre Climbing Foundation Key Project of China, Jiangsu Hengrui Pharmaceuticals. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Serum exosomal miR-377-3p and miR-381-3p as diagnostic biomarkers in colorectal cancer.

Aim: This study aimed to identify specific and sensitive exosomal miRNAs in diagnosing patients with colorectal cancer (CRC). Methods: Serum exosomes were isolated from 175 CRC patients and 172 healthy donors by ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting. Exosomal miRNA expression was detected by quantitative PCR and the results analyzed by receiver operating characteristic analysis to illuminate the diagnostic accuracy. Results: Both exosomal miR-377-3p and miR-381-3p were downregulated in CRC patients as well as in early-stage patients compared with healthy donors; they could serve as circulating biomarkers of diagnosis, including early diagnosis, for CRC, possessing favorable diagnostic efficiency. Conclusion: Exosomal miR-377-3p and miR-381-3p levels were downregulated in CRC patients and may be useful as novel and specific biomarkers for the diagnosis of CRC, especially early-stage CRC.

Major depressive symptoms in breast cancer patients with ovarian function suppression: a cross-sectional study comparing ovarian ablation and gonadotropin-releasing hormone agonists.

BACKGROUND: Ovarian function suppression (OFS) is indicated in premenopausal women with early or metastasis breast cancer, which may be achieved with similar effect by gonadotropin-releasing hormone agonists (GnRHa) or ovarian ablation (OA). We examined whether there were differences in major depressive symptoms outcomes and its associated factors between gonadotropin-releasing hormone agonists (GnRHa) and ovarian ablation (OA) in premenopausal breast cancer patients. METHODS: Premenopausal breast cancer patients from seven hospitals who received OFS participated in the study between June 2019 and June 2020. The correlated variable was the type of ovarian suppression, categorized as either OA (n = 174) or GnRHa (n = 389). Major depressive symptoms was evaluated using the Patient Health Questionnaire (PHQ-9), and the Female Sexual Function Index questionnaire was used to assess sexual function. RESULTS: A total of 563 patients completed the surveys. The mean PHQ-9 sum score was slightly lower in the GnRHa cohort than in the OA cohort (11.4 ± 5.7 vs. 12.8 ± 5.8, P = 0.079). There were significantly fewer patients with major depressive symptoms (PHQ-9 ≥ 15) in the GnRHa cohort (31.1% vs. 40.2%, Exp (B)=1.805, P=0.004). Further, breast-conserving surgery and sexual dysfunction were negatively correlated with major depressive symptoms [mastectomy vs. breast-conserving: Exp (B) = 0.461, P <0.001;[sexual dysfunction vs. normal: Exp (B) = 0.512, P = 0.001]. CONCLUSIONS: This is the first study to demonstrate that GnRHa results in more favorable depressive symptoms outcomes than OA. Moreover, most patients preferred alternatives to their OFS treatment. These findings can contribute to improving and alleviating the adverse effects of OFS.

Tumor-associated exosomal miRNA biomarkers to differentiate metastatic vs. nonmetastatic non-small cell lung cancer.

Background: Exosomal microRNAs (miRNAs) are proposed to be excellent candidate biomarkers for clinical applications. However, little is known about their potential value as diagnostic biomarkers for metastatic non-small cell lung cancer (NSCLC). Methods: In this study, microarrays were used to determine distinct miRNA profiles of plasma exosomes in a discovery cohort of healthy donors, metastatic NSCLC and nonmetastatic NSCLC patients. Three potential candidate miRNAs were selected based on the differential expression profiles. The discovery set data were validated by quantitative real-time polymerase chain reaction using a validation cohort. Results: NSCLC patients (n = 80) and healthy controls (n = 30) had different exosome-related miRNA profiles in plasma. Results demonstrated that the level of let-7f-5p was decreased in plasma exosomes of NSCLC patients (p < 0.0001). Further analysis of three differentially expressed miRNAs revealed that miR-320a, miR-622 and let-7f-5p levels could significantly segregate patients with metastatic NSCLC from patients with nonmetastatic NSCLC (p < 0.0001, p < 0.0001 and p = 0.023, respectively). In addition, the combination of let-7f-5p, CEA and Cyfra21-1 generated an area under the curve (AUC) of 0.981 for the diagnosis of NSCLC patients, and the combination of miR-320a, miR-622, CEA and Cyfra21-1 had an AUC of 0.900 for the diagnosis of patients with metastatic NSCLC. Conclusions: This novel study demonstrated that plasma exosomal miRNAs are promising noninvasive diagnostic biomarkers for metastatic NSCLC.

Tumor-derived exosomal proteins as diagnostic biomarkers in non-small cell lung cancer.

Accumulating evidence supports a role for exosomal protein in diagnosis. The purpose of this study was to identify the tumor-derived exosomal biomarkers in the serum that improve the diagnostic value in Chinese non-small cell lung cancer (NSCLC) patients. Serum exosomes were isolated from healthy donors (n = 46) and NSCLC patients (n = 125) by ultracentrifugation and were characterized using transmission electron microscopy, qNano, and immunoblotting. Proteomic profiles (by mass spectrometry) revealed multiple differentially expressed proteins in the healthy and NSCLC groups. The exosomal expression levels of alpha-2-HS-glycoprotein (AHSG) and extracellular matrix protein 1 (ECM1) increased significantly in the NSCLC patients compared to the healthy group. Alpha-2-HS-glycoprotein showed diagnostic values with a maximum area under the receiver operating characteristic curve (AUC) as 0.736 for NSCLC vs healthy individuals (P < .0001) and 0.682 for early stage NSCLC vs healthy individuals (P < .01). Extracellular matrix protein 1 showed the diagnostic capacity with AUC values of 0.683 (P < .001) and 0.656 (P < .05) in cancer and early stage NSCLC compared to healthy individuals. When AHSG was combined with ECM1, the AUCs were 0.795 and 0.739 in NSCLC and early stage patients, respectively. Taken together, the combination of AHSG, ECM1, and carcinoembryonic antigen improved the diagnostic potential of NSCLC. The diagnosis values were AUC of 0.938 for NSCLC and 0.911 for early stage NSCLC vs healthy individuals. Our results suggest that novel proteomic signatures found in serum exosomes of NSCLC patients show potential usefulness as diagnostic tools.

Tumor-derived exosomal miRNA-320d as a biomarker for metastatic colorectal cancer.

BACKGROUND: To identify specific exosomal microRNAs (miRNAs) as serum biomarkers for prediction of metastasis in patients with colorectal cancer (CRC). MATERIALS AND METHODS: Serum exosomes were isolated from patients with metastatic CRC (n = 34) and non-metastatic CRC (n = 108) by ultracentrifugation and characterized using transmission electron microscopy, qNano, and Western blot. Differential exosomal miRNAs were screened by sequencing and validated by qPCR in metastatic and non-metastatic CRC patients. RESULTS: After sequence analysis, KEGG analysis showed that differential genes were associated with Rap1 signaling pathway and pathways in cancer, 6 upregulated exosomal miRNAs (miR-224-5p, miR-548d-5p, miR-200a-3p, miR-320d, miR-200b-3p, and miR-1246), and 3 downregulated exosomal miRNAs (novel_246, novel_301, and miR-27a-5p) were screened with fold change >1.5, among which miR-320d was selected as the best candidate involved in CRC metastasis. Validation analysis revealed exosomal miR-320d could significantly distinguish metastatic from non-metastatic CRC patients (P = .019), with AUC of 0.633 for the diagnosis of patients with metastatic CRC. Besides, the combination of miR-320d and CEA had an area under curve (AUC) of 0.804 for the diagnosis of patients with metastatic CRC. CONCLUSION: Serum exosomal miR-320d is a promising non-invasive diagnostic biomarker for distinguishing metastatic from non-metastatic CRC.

Circulating exosomes contain protein biomarkers of metastatic non-small-cell lung cancer.

The present study aimed to investigate the overall changes in exosomal proteomes in metastatic and non-metastatic non-small-cell lung cancers (NSCLC) and healthy human serum samples, and evaluate the potential of serum exosomal biomarkers to predict NSCLC metastasis. Tandem mass tags combined with multidimensional liquid chromatography and mass spectrometry analysis were used for screening the proteomic profiles of serum samples. Quantitative proteome, significant pathway, and functional categories of patients with metastatic and non-metastatic NSCLC and healthy donors were investigated. In total, 552 proteins of the 628 protein groups identified were quantified. Bioinformatics analysis indicated that quantifiable proteins were mainly involved in multiple biological functions, metastasis-related pathways. Moreover, lipopolysaccharide-binding proteins (LBP) in the exosomes were found to be well distinguished between patients with metastatic and patients with non-metastatic NSCLC. Area under the curve (AUC) was 0.803 with a sensitivity of 83.1% and a specificity of 67% (P < .0001). Circulating LBP were also well distinguishable between metastatic and non-metastatic NSCLC, the AUC was 0.683 with a sensitivity of 79.5% and a specificity of 47.2% (P = .005). This novel study provided a reference proteome map for metastatic NSCLC. Patients with metastatic and non-metastatic NSCLC differed in exosome-related proteins in the serum. LBP might be promising and effective candidates of metastatic NSCLC.

[Efficacies of aromatase inhibitors in the treatment of hormone dependent metastatic breast cancer in postmenopausal women: a report of 148 cases].

OBJECTIVE: To evaluate the clinical efficacies of aromatase inhibitors in the treatment of postmenopausal metastatic breast cancer. METHODS: A total of 148 postmenopausal women (including bilateral ovariectomy) with hormone dependent metastatic breast cancer receiving aromatase inhibitors (letrozole, anastrozole or exemestane) were analyzed retrospectively. Their clinical efficacies were evaluated. RESULTS: The median progression-free survival (PFS) was 6.5 months and the clinical benefit rate 63.5%. And the rates of PFS of patients on first-line and second-line or above treatments were 9.0 (95% CI: 6.95-11.05) and 3.0 months (95% CI: 1.8-10.1) respectively. The clinical benefit rates of two groups were 74.2% and 26.3% respectively. CONCLUSION: Aromatase inhibitors are both efficacious and well-tolerated for patients of postmenopausal metastatic breast cancer. It may be recommended as a first-line therapy for postmenopausal women with hormone dependent metastatic breast cancer.

Efficacy of capecitabine-based combination therapy and single-agent capecitabine maintenance therapy in patients with metastatic breast cancer.

OBJECTIVE: The purpose of this study was to observe the efficacy and toxicities of capecitabine-based chemotherapy and capecitabine monotherapy as maintenance therapy in the treatment of metastatic breast cancer (MBC). PATIENTS AND METHODS: A total of 98 MBC patients were treated with capecitabine combined with vinorelbine (NX). RESULTS: The median number of treatment was 6 cycles (1-7 cycles). There were two cases of complete remission (CR), 58 partial remission, 27 stable disease (SD), 11 progression disease. The overall response rate (ORR) (CR + PR) was 61.2%. The clinical benefit rate (CBR) was 75.5%. Fifty of effective patients received with capecitabine monotherapy as maintenance therapy. The ORR (CR + PR) was 4%. The CBR was 48%. The median progression-free survival (PFS) was 12 months. In maintenance therapy or not, the median post metastasis survival rate (MSR) was 63 and 28 months, respectively. In the combination therapy group, the major grade 3/4 toxicities included hand-foot syndrome (3.1%), skin pigmentation (2.0%), diarrhoea and abdominal distension (5.1%), stomatitis (1.0%), and leukopenia (20.4%). CONCLUSIONS: Capecitabine-based combination therapy and single-agent capecitabine maintenance therapy were well tolerated and effective to MBC.

Clinicopathological features and prognosis of breast cancer combined with symptomatic bone marrow metastases: A 10-year, single-center, real-world study of 67 cases.

PURPOSE: Bone marrow metastasis (BMM) is uncommon in breast cancer (BC), and early diagnosis is challenging. BMM lacks definitive treatment options and poses a great threat to the survival of patients. Herein, we investigated the clinical features, prognosis, and factors affecting the prognosis of BC patients with symptomatic BMM to help improve the understanding of this disease and provide effective diagnostic and treatment strategies. METHODS: Clinical data of 67 patients with BC and BMM were retrospectively analyzed for clinical characteristics, treatment, and prognosis of BMM. Univariate and multivariate analyses were performed to determine factors affecting overall survival following BMM (BMMOS). RESULTS: Among patients with BMM, 86.6% were diagnosed after bone metastasis (BM), while 13.4% were diagnosed simultaneously with BM. A total of 73.1%, 13.4%, and 13.4% of the patients had hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) tumors, HER2+ tumors, and triple-negative tumors, respectively. The most common symptoms of BMM were the coexistence of anemia and thrombocytopenia (26.9%), anemia (19.4%), and pancytopenia (17.9%). The median BMMOS was 7.6 months (95% CI, 3.9-11.3). Univariate and multivariate analyses showed that BMMOS was associated with platelet count <75 × 109 /L at the time of BMM diagnosis. The BMMOS of patients who underwent endocrine therapy, combined chemotherapy, and mono-chemotherapy after BMM was 15.7, 9.7, and 8.6 months, respectively, whereas that of untreated patients was 2.9 months, and the difference among the results was statistically significant (χ2  = 20.102, p < 0.0001). Changes in patient hemogram and/or body temperature during treatment were consistent with the overall effect of the disease (p < 0.0001). CONCLUSION: BMM should be considered in BC patients with BM, an unexplained reduction in hemogram parameters, especially anemia and thrombocytopenia, and/or fever without chills. Active, effective, individualized treatment strategies can prolong BMMOS.

Novel insights into aerobic denitrifying bacterial communities augmented denitrification capacity and mechanisms in lake waters.

Scanty attention has been paid to augmenting the denitrification performance of polluted lake water by adding mix-cultured aerobic denitrifying bacterial communities (Mix-CADBCs). In this study, to solve the serious problem of nitrogen pollution in lake water bodies, aerobic denitrifying bacteria were added to lake water to enhance the nitrogen and carbon removal ability. Three Mix-CADBCs were isolated from lake water and they could remove >94 % of total nitrogen and dissolved organic carbon, respectively. The balance of nitrogen analysis shown that >70 % of the initial nitrogen was converted to gaseous nitrogen, and <11 % of the initial nitrogen was converted into microbial biomass. The batch experiments indicated that three Mix-CADBCs could perform denitrification under various conditions. According to the results of nirS-type sequencing, the Hydrogenophaga sp., Prosthecomicrobium sp., and Pseudomonas sp. were dominated genera of three Mix-CADBCs. The analysis of network indicated Pseudomonas I.Bh25.14 and Vogsella LIG4 were correlated with the removal of total nitrogen (TN) and dissolved organic carbon in the Mix-CADBCs. Compared with lake raw water, the addition of three Mix-CADBCs could promote the denitrification capacity (the removal efficiencies of TN > 78.72 %), microbial growth (optical density increased by 0.015-0.138 and the total cell count increased by 2 times), and organic degradation ability (the removal efficiency chemical oxygen demand >38 %) of lake water. In general, the findings of this study demonstrated that Mix-CADBCs could provide a new perspective for biological treatment lake water body.

Nitrogen reduction by aerobic denitrifying fungi isolated from reservoirs using biodegradation materials for electron donor: Capability and adaptability in the lower C/N raw water treatment.

Biological denitrification was considered an efficient and environmentally friendly way to remove the nitrogen in the water body. However, biological denitrification showed poor nitrogen removal performance due to the lack of electron donors in the low C/N water. In this study, three novel aerobic denitrifying fungi (Trichoderma sp., Penicillium sp., and Fusarium sp.) were isolated and enhanced the performance of aerobic denitrification of fungi in low C/N water bodies combined with polylactic acid/polybutylene adipate-co-terephthalate (PLA/PBAT). In this work, the aerobic denitrifying fungi seed were added to denitrifying liquid medium and mixed with PLA/PBAT. The result showed that Trichoderma sp., Penicillium sp., and Fusarium sp. could reduce 89.93 %, 89.20 %, and 87.76 % nitrate. Meanwhile, the nitrate removal efficiency adding PLA/PBAT exceeded 1.40, 1.68, and 1.46 times that of none. The results of material characterization suggested that aerobic denitrifying fungi have different abilities to secrete proteases or lipases to catalyze ester bonds in PLA/PBAT and utilize it as nutrients in denitrification, especially in Penicillium brasiliensis D6. Besides, the electron transport system activity and the intracellular ATP concentration were increased significantly after adding PLA/PBAT, especially in Penicillium brasiliensis D6. Finally, the highest removal efficiency of total nitrogen in landscape water by fungi combined with PLA/PBAT was >80 %. The findings of this work provide new insight into the possibility of nitrogen removal by fungi in low C/N and the recycling of degradable resources.

Aerobic denitrifying using actinobacterial consortium: Novel denitrifying microbe and its application.

The aerobic denitrifying capacity of actinomycete strain has been investigated recently, while little is known about nitrogen and carbon substrate removal by mix-cultured aerobic denitrifying actinobacteria (Mix-CADA) community. Hence, three Mix-CADA consortiums, named Y23, X21, and Y27, were isolated from urban lakes to investigate their aerobic denitrification capacity, and their removal efficiency for nitrate and dissolved organic carbon were >97 % and 90 %, respectively. Illumina Miseq sequencing revealed that Streptomyces was the most dominant genus in the Mix-CADA consortium. Network analysis indicated that Streptomyces exfoliates, as the core species in the Mix-CADA consortium, majorly contributed to dissolved organic carbon and total nitrogen reduction. Moreover, the three Mix-CADA consortiums could remove 78 % of the total nitrogen and 61 % of the permanganate index from the micro-polluted l water. Meanwhile, humic-like was significantly utilized by three Mix-CADA consortiums, whereas Mix-CADA Y27 could also utilize aromatic protein and soluble microbial by-product-like in the micro-polluted raw water purification. In summary, this study will offer a novel perspective for the purification of micro-polluted raw water using the Mix-CADA consortium.

Characterization of non-taste & odor produced aerobic denitrification actinomycetes strains Streptomyces spp. isolated from reservoir ecosystem: Denitrification performance and carbon source metabolism.

The aerobic denitrification performance of actinomycetes was investigated. Two strains of actinomycetes were isolated and identified as Streptomyces sp. LJH-12-1 and Streptomyces diastatochromogenes LJH-12-2. Strain LJH-12-1 could remove 94% of organic carbon and 91% of total nitrogen. Meanwhile, strain LJH-12-2 could reduce 96% of organic carbon and 93% of total nitrogen. Two strains of actinomycetes revealed excellent carbon source metabolism activity. Moreover, the total nitrogen removal efficiencies were 69%, and 54%, respectively for strains LJH-12-1, and LJH-12-2 during the micro-polluted landscape raw water treatment. Futhermore, strains LJH-12-1 and LJH-12-2 could utilize aromatic proteins, soluble microbial products, and humic acid to drive aerobic denitrification processes in the landscape water bodies. These results will provide a new insight into applying aerobic denitrification actinomycetes to treat micro-polluted water bodies.

Effects of copper sulfate algaecide on the cell growth, physiological characteristics, the metabolic activity of Microcystis aeruginosa and raw water application.

Harmful cyanobacteria blooms (HCBs) occurred frequently and become a serious scientific challenge. Copper sulfate (CuSO4) is a broad-spectrum chemical algaecide to control algae blooms. Herein, the Microcystis aeruginosa was exposed to different CuSO4 (0.0, 0.2 and 0.5 mg/L) to assess the variations in algal physiological process and metabolic profiles. The results indicated that exposure to CuSO4 of 0.5 mg/L at 72 h could significantly inhibit the cell growth and photosynthetic capacity of M. aeruginosa, including chl-a content and chlorophyll fluorescence parameters. Plasma membrane damage causing cell lysis of M. aeruginosa increased the K+ release. The increase of SOD and CAT suggested that CuSO4 treatment caused oxidative stress in algal cells. Different doses of CuSO4 modified the carbon metabolic potential, algal cells had their unique metabolic mode thereby. Moreover, the research further verified that CuSO4 would also inhibit algal growth and change algal community structure in site-collected water application. Overall, laboratory results of M. aeruginosa to CuSO4 and site-collected water application of algal responses to CuSO4 might be conducive to uncovering the controlling mechanism of algae and the potential effect of carbon cycling in an ecological environment.

Dalpiciclib and pyrotinib in women with HER2-positive advanced breast cancer: a single-arm phase II trial.

CDK4/6 inhibitors have shown a synergistic effect with anti-HER2 therapy in hormone receptor (HR)-positive and HER2-positive breast cancer (BC). In this phase 2 study (NCT04293276), we aim to evaluate a dual-oral regimen of CDK4/6 inhibitor dalpiciclib combined with HER2 tyrosine kinase inhibitor pyrotinib as front-line treatment in women with HER2-positive advanced BC (n = 41) including those with HR-negative disease. The primary endpoint is the objective response rate, and secondary endpoints include progression-free survival (PFS), overall survival (OS), and safety. With a median follow-up of 25.9 months, 70% (28/40) of assessable patients have a confirmed objective response, meeting the primary endpoint. The median PFS is 11.0 months (95% CI = 7.3-19.3), and OS data are not mature. The most common grade 3 or 4 treatment-related adverse events (AEs) are decreased white blood cell count (68.3%), decreased neutrophil count (65.9%), and diarrhea (22.0%). Most AEs are manageable, and no treatment-related deaths occur. These findings suggest that this combination may have promising activity and manageable toxicity. Further investigation is needed.

Promoted aerobic denitrification through denitrifying fungal communities: Co-occurrence patterns and treatment of low C/N micro-polluted water.

Despite the growing interest in using mixed-culture aerobic denitrifying fungal flora (mixed-CADFF) for water remediation, there is limited research on their nitrogen removal performance in low C/N polluted water bodies. To address this knowledge gap, we isolated three mixed-CADFFs from overlying water in urban lakes to evaluate their removal performance. The total nitrogen (TN) removal efficiencies were 93.60 %, 94.64 %, and 95.18 %, while the dissolved organic carbon removal efficiencies were 96.64 %, 95.12 %, and 96.70 % for mixed-CADFF LN3, LN7, and LN15, respectively in the denitrification medium under aerobic conditions at 48 h cultivation. The three mixed-CADFFs could utilize diverse types of low molecular weight carbon sources to drive the aerobic denitrification processes efficiently. The optimal C/N ratio for the mixed-CADFFs were C/N = 10, and then C/N = 15, 7, 5, and 2. The high-throughput sequencing analysis of three mixed-CADFFs indicated that Eurotiomycetes, Cystobasidiomycetes, and Sordariomycetes were the dominant class in the communities at class level. The network analysis showed that the rare fungal species, such as Scedosporium dehoogii Saitozyma, and Candida intermedia presented positively co-occurred with the TN removal and organic matter reduction capacity. Immobilization mixed-CADFFs treatment raw water experiments indicated that three mixed-CADFFs could reduce nearly 62.73 % of TN in the low C/N micro-polluted raw water treatment. Moreover, the cell density and cell metabolism indexes were also increased during the raw water treatment. This study will provides new insight into resource utilization of the mixed-culture aerobic denitrifying fungal community in field of environment restoration.

Distress Thermometer in breast cancer: systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aimed to reach a summarised estimate of distress prevalence screened by Distress Thermometer (DT) among patients with breast cancer and compare different pooled prevalence estimated between different subgroups. METHODS: Two independent interviewers conducted a systematic search from PubMed, EMBASE, Ovid and Cochrane Library and checked related reviews and meta-analyses for eligible studies. The studies that identified distress of patients with breast cancer with DT were included. After extracting demographic characteristics and distress prevalence, the pooled analysis and the forest plot were completed by using STATA V.12.0 software. We conducted a subgroup analysis based on demographic and methodological characteristics of the studies. The publication bias was estimated by funnel plot. RESULTS: Seventeen studies describing 3870 patients with breast cancer were included in this meta-analysis. The distress prevalence of patients with breast cancer varied from 25.3% to 71.7% among these studies. The pooled distress prevalence was 50% (95% CI 49% to 52%) for the overall sample. The pooled distress prevalence rates in DT ≥7, DT ≥5 and DT ≥4 subgroups were 37% (95% CI 35% to 40%), 45% (95% CI 40% to 49%) and 62% (95% CI 60% to 65%), respectively. The distress prevalence had statistically significant differences between subgroups, which were differentiated by the initial time of distress identified, papers' publication time, patients' average age and country. There was no publication bias among the included studies. CONCLUSION: The distress prevalence was high among patients with breast cancer. Routine and timely screening of distress for patients with breast cancer is of great significance in oncology management.