Drug Analysis of Voriconazole Combined with Granulocyte Colony Stimulating Factor.

BACKGROUND: The aim of the study was to improve the clinical cognition of leukemia-like reaction caused by voriconazole and granulocyte colony-stimulating factor and to avoid misdiagnosis or delayed diagnosis. METHODS: A case of drug analysis of Voriconazole combined with granulocyte colony stimulating factor was retrospectively analyzed and related literature was reviewed. RESULTS: Blood routine of the patient on July 29: WBC 13.48 x 109/L, neutrophil 85.3%, lymphocyte 13.4%, hemoglobin 111 g/L, platelet 285 x 109/L. Vancomycin was given to prevent intracranial infection. Lumbar puncture was performed on July 30, cerebrospinal fluid was sent for routine and biochemical examination, leukocytes were 0.15 x 109/L, monocytes 45%, polynuclear cells 55%, protein 1.172 g/L, Acinetobacter baumannii and Candida clorbicus were detected in sputum culture, vancomycin and meropenem static sites were given to prevent intracranial secondary infection. Fungi were detected in urine culture, and voriconazole was given to prevent fungal infection. Blood routine: White blood cell 0.61 x 109/L, neutrophil 23%, lymphocyte 73.8%, red blood cell 2.65 x 1012/L, hemoglobin 77 g/L, platelet 17 x 109/L, bone marrow was extracted after medication. Bone marrow images show poor myelodysplasia, with granulocytes dominated by protoearly cells. Subsequent flow cytometry, chromosomal karyotype, and fusion gene analysis were performed to exclude the possibility of leukemia. Flow cytometry showed that the proportion of myeloid primordial cells was not high, the granulocytes were mainly at the early and young stage, no abnormal phenotype was observed in erythrocytes, monocytes and NK cells, no obvious mature B lymphocytes were observed, and the ratio of CD4+/CD8+ was decreased. Karyotype results showed that there was no mitotic phase. The results of fusion gene analysis showed that the fusion gene was negative or lower than the detection sensitivity. Voliconazole was stopped first, and granulocyte colony stimulating factor was stopped 3 days later. Two weeks later, blood and bone marrow images basically recovered, white blood cell 7.88 x 109/L, neutrophil 46.3%, lymphocyte 48.2%, hemoglobin 126 g/L, platelet 142 x 109/L, bone marrow hyperplasia active. The proportion of three series is roughly normal. CONCLUSIONS: The reason for the occurrence of leukemia-like reaction in this patient was considered to be related to voriconazole and granulocyte colony stimulating factor, cessation of voriconazole and granulocyte colony stimulating factor, and recovery of blood and bone marrow images. In the clinical use of voriconazole and granulocyte colony stimulating factor, close attention should be paid to the drug interaction and individualized medication should be carried out to ensure the safety of medication.

Titanium Dioxide Nanoparticles Induce Maternal Preeclampsia-like Syndrome and Adverse Birth Outcomes via Disrupting Placental Function in SD Rats.

The escalating utilization of titanium dioxide nanoparticles (TiO2 NPs) in everyday products has sparked concerns regarding their potential hazards to pregnant females and their offspring. To address these concerns and shed light on their undetermined adverse effects and mechanisms, we established a pregnant rat model to investigate the impacts of TiO2 NPs on both maternal and offspring health and to explore the underlying mechanisms of those impacts. Pregnant rats were orally administered TiO2 NPs at a dose of 5 mg/kg body weight per day from GD5 to GD18 during pregnancy. Maternal body weight, organ weight, and birth outcomes were monitored and recorded. Maternal pathological changes were examined by HE staining and TEM observation. Maternal blood pressure was assessed using a non-invasive blood analyzer, and the urinary protein level was determined using spot urine samples. Our findings revealed that TiO2 NPs triggered various pathological alterations in maternal liver, kidney, and spleen, and induced maternal preeclampsia-like syndrome, as well as leading to growth restriction in the offspring. Further examination unveiled that TiO2 NPs hindered trophoblastic cell invasion into the endometrium via the promotion of autophagy. Consistent hypertension and proteinuria resulted from the destroyed the kidney GBM. In total, an exposure to TiO2 NPs during pregnancy might increase the risk of human preeclampsia through increased maternal arterial pressure and urinary albumin levels, as well as causing fetal growth restriction in the offspring.

Clinical Characteristics and Diagnosis of Ph-Positive Mixed Phenotype Acute Leukemia.

BACKGROUND: The goal was to improve the clinical cognition of Ph-positive mixed phenotype acute leukemia and avoid misdiagnosis or delayed diagnosis. METHODS: The clinical manifestations and laboratory results (bone marrow cell morphology, multiparameter flow cytometry, and cytogenetics) of a case of Ph-positive mixed phenotype acute leukemia were analyzed, and related literature was reviewed. RESULTS: Blood routine: WBC 386.35 x 109/L, HGB 117.00 g/L, PLT 31 x 109/L; 80% of the original cells can be seen by artificial classification. Morphological examination of bone marrow cells showed that the proliferation of nucleated cells was obviously active, and the original cells accounted for 76%. The size of the original cells was somewhat uniform, most of the cells had less mass, were stained light grayish blue, the cytoplasm particles were not obvious, the nuclei were mostly round or quasi-round, some of them showed distortion and nuclear notch, and the chromatin was coarse. Some of the cells were rich in mass, small azurin granules were seen, the nuclei were regular, most of them were round, the chromatin was fine, the myeloperoxidase and esterase staining were negative, the eosinophils accounted for 2.5%, and the basophils accounted for 0.5%. Flow cytometry immunotyping: Two groups of abnormal cells were seen in the bone marrow. 1. A group included 12.32% of nuclear cells and showed abnormal myeloid primitive cell phenotype. Main expression: CD117, CD34, CD38, HLA-DR, CD33, CD64, CD123, weak expression: CD13, CD19. 2. The other group included 45.61% of the nuclear cells and had a B-lymphoblastic phenotype. Main expression: CD34, CD38, HLA-DR, CD123, CD19, CD10, CD9, cCD79a, TDT, weak expression of CD13, CD22. Mixed phenotype acute leukemia (M/B) immunophenotype was considered. Chromosome: 46,XY,t(9; 22)(q34;q11.2) [20]. BCR-ABL (P210) fusion gene was positive. CONCLUSIONS: Mixed phenotype acute leukemia (MPAL) is a rare type of malignant hematologic disease. Its diagnosis is based on the comprehensive evaluation of bone marrow cell morphology, immunophenotype, molecular and cytogenetic features.

General practitioners' attitudes towards and frequency of collaboration with pharmacists in China: a cross-sectional study.

BACKGROUND: Building interprofessional working relationships between general practitioners (GPs) and pharmacists is essential to ensure high-quality patient care. However, there is limited Chinese literature on GP-pharmacist collaboration, and few studies have explored GPs' experiences with pharmacist integration into general practices. This study aimed to investigate GPs' attitudes towards and frequency of collaboration with pharmacists in China. METHODS: This cross-sectional study used an online self-administered questionnaire integrating two scales, ATCI-GP and FICI-GP, which had been translated and validated to investigate 3,248 GPs from February 15 to March 15, 2023 across Zhejiang Province, China. Descriptive analyses were used, and the factors associated with GPs' frequency of collaboration with pharmacists were explored using logistic regression analysis. RESULTS: A total of 2,487 GPs (76.6%) responded and consented to participate in the survey; 52.3% were male and the mean age was 35.4 years. Most GPs agreed that they shared common goals and objectives with pharmacists when caring for patients (90.0%), and pharmacists were open to working with them on patients' medication management (80.8%). However, half of the GPs did not change or seldom changed the patient's medication on the pharmacist's advice (51.4%). Logistic regression analysis showed that GPs who were older and had more years of practice were more likely to agree that pharmacists were willing to collaborate, had common goals for treatment and that they would change the patient's medication on the advice of the pharmacist. GPs who had regular communication protocols (adjusted odds ratio1 [aOR1] = 1.88, 95% CI 1.45-2.45; aOR2 = 3.33, 95% CI 2.76-4.02), participated in joint continuing education (aOR1 = 1.87, 95% CI 1.44-2.43; aOR2 = 2.27, 95% CI 1.91-2.70), provided recommendations for medication review (aOR1 = 3.01, 95% CI 2.07-4.38; aOR2 = 3.50, 95% CI 2.51-4.86), and communicated with pharmacists during resident training (aOR1 = 2.15, 95% CI 1.78-2.60; aOR2 = 1.38, 95% CI 1.18-1.62) were associated with a more positive attitude towards and higher frequency of cooperation. CONCLUSIONS: GPs in China displayed a positive attitude towards cooperating with pharmacists, but they did not demonstrate a similar level of practice. As environmental determinants impact interdisciplinary collaboration, healthcare managers and policy-makers need to implement measures that foster a supportive environment conducive to interdisciplinary collaboration.

Association between blood heavy metals and lung cancer risk: A case-control study in China.

BACKGROUND: Exposure to various metals has been reported to lead to lung cancer. However, few studies focused on the combined effects of metal mixture. OBJECTIVE: To explore the relationship between metal mixture and lung cancer patients. METHODS: Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of 8 heavy metals (V, Cr, Mn, Se, Mo, Cd, Ba and Pb) in serum samples of 86 cases and 105 controls in the Tianjin Lung Cancer Cohort. Logistic regression models were used to estimate the effect of each metal on the risk of lung cancer. The restricted cubic spline function was applied to describe the dose-response relationship between various metal concentrations and lung cancer risk. Bayesian Kernel Machine Regression (BKMR), Weighted Quantile Sum (WQS) and Quantile G-Computation (QGC) were employed to explore the effects of metal mixtures as a whole on lung cancer. RESULTS: An increased risk of lung cancer was associated with higher blood Mo concentration (adjusted OR = 2.94, 95% CI = 1.03-8.74 for tertile 2 vs. tertile 1). Higher Se concentration in blood may have protective effects on the risk of lung cancer (adjusted OR = 0.18, 95% CI = 0.06-0.51 for tertile 3 vs. tertile 1, p-trend <0.001). In addition, Se and Cd may have an antagonism effect on the occurrence of lung cancer (RERI and 95% CI = -0.95 [-31.77, -0.07]; AP and 95% CI = -0.95 [-5.16 -0.74]). Although the metal mixture did not show a significant effect on lung cancer as a whole, this may be due to the offsetting effect between positive and negative effects. CONCLUSIONS: Our research indicates that Se has a promising anti-cancer application, but it is necessary to prevent the role of Cd that antagonize Se in lung cancer.

Cytochrome P450 Mediated Cyclization in Eunicellane Derived Diterpenoid Biosynthesis.

Terpene cyclization, one of the most complex chemical reactions in nature, is generally catalyzed by two classes of terpene cyclases (TCs). Cytochrome P450s that act as unexpected TC-like enzymes are known but are very rare. In this study, we genome-mined a cryptic bacterial terpenoid gene cluster, named ari, from the thermophilic actinomycete strain Amycolatopsis arida. By employing a heterologous production system, we isolated and characterized three highly oxidized eunicellane derived diterpenoids, aridacins A-C (1-3), that possess a 6/7/5-fused tricyclic scaffold. In vivo and in vitro experiments systematically established a noncanonical two-step biosynthetic pathway for diterpene skeleton formation. First, a class I TC (AriE) cyclizes geranylgeranyl diphosphate (GGPP) into a 6/10-fused bicyclic cis-eunicellane skeleton. Next, a cytochrome P450 (AriF) catalyzes cyclization of the eunicellane skeleton into the 6/7/5-fused tricyclic scaffold through C2-C6 bond formation. Based on the results of quantum chemical computations, hydrogen abstraction followed by electron transfer coupled to barrierless carbocation ring closure is shown to be a viable mechanism for AriF-mediated cyclization. The biosynthetic logic of skeleton construction in the aridacins is unprecedented, expanding the catalytic capacity and diversity of P450s and setting the stage to investigate the inherent principles of carbocation generation by P450s in the biosynthesis of terpenoids.

WeChat official accounts' posts on medication use of 251 community healthcare centers in Shanghai, China: content analysis and quality assessment.

Background: The dissemination of online health information (OHI) on medication use via WeChat Official Accounts (WOAs) is an effective way to help primary care practitioners (PCPs) address drug-related problems (DRPs) in the community. Although an increasing number of primary care institutions in China have published WOA posts on medication use, their content and quality have not yet been assessed. Objective: This study aimed to explore the general features and content of WOA posts on medication use published by community healthcare centers (CHCs) in Shanghai, China and to assess their quality of content. It also aimed to explore the factors associated with the number of post views. Methods: From June 1 to October 31, 2022, two coauthors independently screened WOA posts on medication use published throughout 2021 by the CHCs in Shanghai. Content analysis was performed to analyze their general features (format, length, and source, etc.) and content (types of medicines and diseases). The QUEST tool was used to assess the quality of the posts. We compared the differences among posts published by CHCs in central urban areas and suburban areas, and used multiple linear regression to explore the factors associated with the number of post views. Results: A total of 236 WOAs of interest published 37,147 posts in 2021, and 275 (0.74%) of them were included in the study. The median number of post views was 152. Thirty percent of the posts were reviewed by the CHCs' staff before publication and only 6% provided information on PCPs' consultations. The most commonly mentioned medicines and diseases in the posts were Chinese patent medicines (37.1%) and respiratory diseases (29.5%). The posts frequently provided information on indications (77%) and usage (56%) but rarely on follow-up (13%) and storage (11%). Of the posts, 94.9% had a total QUEST score < 17 (full score = 28). The median number of post views and total post quality scores did not significantly differ among the CHCs in central urban and suburban areas. In the multiple linear regression model, the number of post views was associated with scores of complementarity (B = 56.47, 95% CI 3.05, 109.89) and conflict of interest (B = -46.40, 95% CI -56.21, -36.60). Conclusion: The quantity and quality of WOA posts on medication use published by CHCs in China need improvement. The quality of posts may partially impact the dissemination effect, but intrinsic causal associations merit further exploration.

Effects of ultrasonic vibration on microstructure and mechanical properties of 1Cr12Ni3MoVN alloy fabricated by directed energy deposition.

Due to the rapid melting and solidification during directed energy deposition (DED) process, the defects and columnar crystals are likely to generate in the deposition layers, which reduce the quality and performance of the whole parts. Therefore, in order to improve the microstructure and mechanical properties of 1Cr12Ni3MoVN alloy manufactured by DED method, ultrasonic vibration (UV) has been employed to assist directed energy deposition process in this work. The results indicate that the high-intensity ultrasonic vibration can weaken the epitaxy growth tendency of crystal grains, and significantly improve plasticity while keeping an approximate strength. In addition, a two-dimensional numerical model is established to simulate the effect of ultrasonic vibration in the molten pool. The simulation results show that ultrasonic vibration remarkably improves the flow velocity and pressure in the molten pool, inducing the cavitation effect that breaks dendritic crystal and affects crystal characteristics. Meanwhile, the acoustic streaming effect changes the thermodynamic conditions and promotes high-temperature diffusion, which uniforms temperature distribution and reduces the temperature gradient in the molten pool. Thus the reduced temperature gradient G and raised solidification growth rate R promote the formation of fine equiaxed crystal characteristics after UV treatment. The product G × R increases and the ratio G/R decreases after UV treatment, resulting in the formation of fine equiaxed crystals.

A Case of AML1/ETO Positive Child with Acute Myeloid Leukemia with Poor Prognosis.

BACKGROUND: The aim was to improve the understanding of an AML1/ETO positive child with acute myeloid leukemia with poor prognosis. METHODS: A case of AML1/ETO positive child with acute myeloid leukemia with poor prognosis was reported. The bone marrow cell morphology, multi-parameter flow cytometry, cytogenetic or molecular genetic test results were analyzed by reviewing relevant literature. RESULTS: The patient was a young girl with clinical manifestations of respiratory tract infection. Bone marrow smears showed that myeloid primordial cells accounted for 13%, some granulocyte cell bodies are enlarged, visible pathological phenomena such as cytoplasmic vacuoles, binuclear grains, ring rods, and pseudo pelgerhuet malformations were seen (Figure 1). Flow cytometry: abnormal myeloid original cells (12.33%), expression of CD34 and HLA - DR, CD38, CD56, part of the expression of CD117, weak expression of CD13, CD33, MPO, CD19, cCD79a (Figure 2). Chromosome karyotype analysis showed that the chromosome karyotype of peripheral blood was 46, XX, t(8;21)(q22;q22). The quantitative detection result of AML1/ETO fusion gene was 42.15%, and mutations of NRAS, ASXL2, TP53 and TET2 genes were detected by second-generation sequencing. Combined with the above results, AML1/ETO positive with acute myeloid leukemia was diagnosed. CONCLUSIONS: Cytogenetics or molecular genetics is the gold standard for identification of positive AML1/ETO fusion gene. Morphological heterogeneity of AML1/ETO positive AML cells is large, which limits the morphological diagnosis of bone marrow cells to a certain extent, and the comprehensive diagnostic efficiency is significantly better than that of morphology. Leukemia fusion gene AML1/ETO refers to the fusion of AML1 gene located on human chromosome 21q22 and ETO gene 8q22, which is the most common fusion gene in acute myeloid leukemia (AML). This paper reports a case of an AML1/ETO positive child with acute myeloid leukemia with poor prognosis admitted to our hospital and reviews relevant literature.

A facile synthesis of highly efficient In2S3 photocatalysts for the removal of cationic dyes with size-dependent photocatalysis.

In this study, a 3D thornball-like hierarchical ß-In2S3, displaying extremely rapid photodegradation of cationic dyes, was synthesized by a facile method. The formation of a uniform thornball-like structure depended on the microwave reaction method and citric acid as the pH regulator. The size of In2S3 was easily adjusted by changing the microwave irradiation time from 5 min to 15 min. The morphology, structure, composition, energy level, charge separation, and surface properties of different-sized In2S3 were characterized. The results showed that In2S3 synthesized in 10 min (In2S3-10) displayed optimal interface property for the electron-hole separation, maximum hydrophilia with most surface negative charges for the surface adsorption, contributing to the complete photodegradation of rhodamine B (RhB) in just 25 minutes of visible light illumination. The photodegradation path of RhB was speculated with four possible paths, including the processes of de-ethylation, open-ring of xanthene, and rupture of carbon-carbon bonds up to the decomposition into small molecules. Finally, the reusability of In2S3-10 was tested, obtaining nearly 96% photodegradation efficiency after sequential 5 cycles.

Establishment and validation of a plasma oncofetal chondroitin sulfated proteoglycan for pan-cancer detection.

Various biomarkers targeting cell-free DNA (cfDNA) and circulating proteins have been tested for pan-cancer detection. Oncofetal chondroitin sulfate (ofCS), which distinctively modifies proteoglycans (PGs) of most cancer cells and binds specifically to the recombinant Plasmodium falciparum VAR2CSA proteins (rVAR2), is explored for its potential as a plasma biomarker in pan-cancer detection. To quantitate the plasma ofCS/ofCSPGs, we optimized an ELISA using different capture/detection pairs (rVAR2/anti-CD44, -SDC1, and -CSPG4) in a case-control study with six cancer types. We show that the plasma levels of ofCS/ofCSPGs are significantly higher in cancer patients (P values, 1.2 × 10-2 to 4.4 × 10-10). Validation studies are performed with two independent cohorts covering 11 malignant tumors. The individuals in the top decile of ofCS-CD44 have more than 27-fold cancer risk (OR = 27.8, 95%CI = 18.8-41.4, P = 2.72 × 10-62) compared with the lowest 20%. Moreover, the elevated plasma ofCS-CD44 could be detected at the early stage of pan-cancer with strong dose-dependent odds risk prediction.

A Case Report of Mixed Phenotype Acute Leukemia with Plasmacytoid Dendritic Cell Proliferation.

BACKGROUND: The goal was to improve the understanding of mixed phenotypic acute leukemia (MPAL) complicated with plasmacytoid dendritic cell (PDC) proliferation. METHODS: A case of mixed phenotype acute leukemia with plasmacytoid dendritic cell hyperplasia was reported. The clinical characteristics, treatment, and prognosis were analyzed by reviewing relevant literature. RESULTS: The patient was a young female with clinical manifestations of splenomegaly and lymph node enlargement. The bone marrow smear showed hyperactive proliferation, 95% of protoblastic cells. The protoblastic cell body is large, more cell mass, stained gray blue, a small amount of azurophilicgranule can be seen in some cytoplasm, pseudopodia, drag tail, and other phenomena. The nucleus was twisted and folded. Chromatin is fine with nucleoli and Auer rods seen in the cytoplasm. Immune typing: Abnormal primordial cells accounted for 44.75%, and the primordial cells expressed both myeloid markers (CD33, CD13, MPO) and T-series markers (CD7, CD5, Ccd3), which were considered MPAL (M/T) according to WHO diagnostic criteria. In addition, a group of plasmoid dendritic cells occupied an increased proportion of 10.31% of nuclear cells. No obvious phenotypic abnormalities were observed. BCR/ABL fusion genes P190/P210 were negative. NRAS, NOTCH1, and DNMT3A mutations were detected by polymerase chain reaction. Combined with the above results, acute mixed cell leukemia (M/T) with plasmacytoid dendritic cell proliferation was diagnosed. CONCLUSIONS: The diagnosis of mixed phenotype acute leukemia with plasmacytoid dendritic cell proliferation needs to be integrated with clinical manifestations, cytomorphology, immunology, cytogenetics, and molecular biology, etc. Disease should be diagnosed and treated as early as possible.

Structural Simplification of Cryptolepine to Obtain Novel Antifungal Quinoline Derivatives against Phytopathogenic Fungi.

A series of quinoline derivatives were designed and synthesized by the structural simplification of cryptolepine and evaluated for their fungicidal activity against six phytopathogenic fungi. Most of these compounds exhibited remarkable activities against Botrytis cinereain vitro. Among them, compounds A18 and L01 showed superior antifungal activity. Significantly, compared to cryptolepine, compound A18 exhibited broad-spectrum inhibitory activities against B. cinerea, Sclerotinia sclerotiorum, Rhizoctonia solani, Phytophthora capsica, Magnaporthe oryzae, and Fusarium graminearum with the respective EC50 values of 0.249, 1.569, 3.915, 0.505, 0.246, and 4.999 µg/mL. Compound L01 displayed the best antifungal activity against B. cinerea with an EC50 value of 0.156 µg/mL. Preliminary mechanistic studies showed that compound A18 could inhibit spore germination, affect the permeability of the cell membrane, increase the content of reactive oxygen species, and affect the morphology of hyphae and cells. Moreover, compound A18 showed excellent in vivo protective effect against B. cinerea, which was more potent than pyrimethanil and equitant to cryptolepine. These results evidenced that compound A18 displayed superior fungicidal activities and could be a potential fungicidal candidate against plant fungal diseases.

ABO blood groups and expression of blood group antigens of epithelial ovarian cancer in Chinese women.

BACKGROUND: ABO blood groups has been associated with risk of several cancers; however, the results for an association with ovarian cancer are inconsistent and little is known about the expression of histo-blood group (ABH) antigens and ABO gene in ovarian tumor tissues. METHODS: To assess the impact of genotype-derived ABO blood types on the risk of EOC, we conducted a case-control study in 1,870 EOC and 4,829 controls. Expression of A and B antigen in 70 pairs of ovarian tumor tissues and adjacent normal tissues were detected by immunohistochemistry. Gene expression and DNA methylation profiling was conducted in ovarian tumor tissues. RESULTS: We identified that blood group A was associated with increased risk for EOC compared to blood group O (OR = 1.18, 95% CI = 1.03-1.36, p = 0.019). Increased frequency of aberrant expression of histo-blood group antigens was observed in patients with blood group A (76.5%) compared to patients with blood group O (21.1%) and B (5.0%) by immunohistochemistry (p < 0.001). ABO gene expression was down-regulated in ovarian tumor tissues compared with paired adjacent normal tissues (p = 0.027). In addition, ABO gene expression was positively correlated with NFYB (r = 0.38, p < 0.001) and inversely correlated with DNA methylation level of four CpG sites on ABO gene (cg11879188, r = - 0.3, p = 0.002; cg22535403, r = - 0.30, p = 0.002; cg13506600, r = - 0.22, p = 0.025; cg07241568, r = - 0.21, p = 0.049) in ovarian tumor tissues. CONCLUSION: We identified blood group A was associated with increased EOC risk in Chinese women and provided the clues of the possible molecular mechanisms of blood group A related to ovarian cancer risk.

Achieving mainstream anammox in biological aerated filter by regulating bacteria community structure.

Although mainstream partial nitrification-anammox (PN-A) is a highly efficient and sustainable wastewater treatment process, it is difficult to achieve and stabilize due to the competition among functional bacteria. In this study, achieving one-stage mainstream anammox via regulating bacteria community structure was studied in a lab-scale biological aerated filter (BAF). The results showed that high free ammonia with 89.57 mg/L, nitrite nitrogen (NO2--N) competition between anammox bacteria (AnAOB) and nitrite oxidizing bacteria (NOB), and backwash regulated the bacteria community structure. After backwash, Candidatus Kuenenia became the dominant bacteria and the relative abundance increased to 5.56 %. In BAF, one-stage mainstream anammox with total nitrogen (TN) being lower than 15 mg/L in the effluent was achieved using lag-time of bacteria activity recovery caused by alternating operation of high and low ammonia nitrogen (NH4+-N), which have great potential applied in municipal wastewater treatment plants (MWWTPs).

Perfluoroalkyl substances (PFASs) as risk factors for breast cancer: a case-control study in Chinese population.

BACKGROUND: Perfluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Recent studies have implicated exposure to PFASs as a risk factor for breast cancer in Europe and America. Little is known about the role of PFASs with respect to breast cancer in the Chinese population. METHODS: Participants who were initially diagnosed with breast cancer at Tianjin Medical University Cancer Institute and Hospital between 2012 and 2016 were recruited as cases. The controls were randomly selected from the participants with available blood samples in the Chinese National Breast Cancer Screening Program (CNBCSP) cohort. Ultimately, we enrolled 373 breast cancer patients and 657 controls. Plasma PFASs were measured by an ultra-performance liquid chromatography (UPLC) system coupled to a 5500 Q-Trap triple quadrupole mass spectrometer. A logistic regression model with least absolute shrinkage and selection operator (LASSO) regularization was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationships between PFASs and breast cancer. The three most predictive variables in the LASSO model were selected from 17 PFASs, which was based on the optimal penalty coefficient (λ = 0.0218) identified with the minimum criterion. Additionally, Bayesian kernel machine regression (BKMR) and quantile g-computation models were applied to evaluate the associations between separate and mixed exposure to PFASs and breast cancer. RESULTS: Perfluorooctanesulfonic acid (PFOS) exhibited the highest concentration in both the cases and controls. Perfluorooctanoic acid (PFOA) and perfluoro-n-decanoic acid (PFDA) were positively associated with breast cancer, and perfluoro-n-tridecanoic acid (PFTrDA) was negatively associated with breast cancer according to both the continuous-PFASs and the quartile-PFASs logistic regression models. Of note, PFOA was associated with the occurrence of estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (ORER+ = 1.47, 95% CI: 1.19, 1.80; ORPR+ = 1.36, 95% CI: 1.09, 1.69; ORHER2 = 1.62, 95% CI: 1.19, 2.21). CONCLUSIONS: Overall, we observed that PFASs were associated with breast cancer in Chinese women. Prospective cohort studies and mechanistic experiments are warranted to elucidate whether these associations are causal.

Widespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction.

Argonaute 2 (AGO2) is a ubiquitously expressed protein critical for regulation of mRNA translation and vital to animal development. AGO2 protein is found in both cytoplasmic and nuclear compartments, and although its cytoplasmic role is well studied, the biological relevance of nuclear AGO2 is unclear. Here, we address this problem in vivo using spermatogenic cells as a model. We find that AGO2 transiently binds both chromatin and nucleus-specific mRNA transcripts of hundreds of genes required for sperm production during male meiosis in mice, and that germline conditional knockout (cKO) of Ago2 causes depletion of the encoded proteins. Correspondingly, Ago2 cKO males show abnormal sperm head morphology and reduced sperm count, along with reduced postnatal viability of offspring. Together, our data reveal an unexpected nuclear role for AGO2 in enhancing expression of developmentally important genes during mammalian male reproduction.

Living biobank-based cancer organoids: prospects and challenges in cancer research.

Biobanks bridge the gap between basic and translational research. Traditional cancer biobanks typically contain normal and tumor tissues, and matched blood. However, biospecimens in traditional biobanks are usually nonrenewable. In recent years, increased interest has focused on establishing living biobanks, including organoid biobanks, for the collection and storage of viable and functional tissues for long periods of time. The organoid model is based on a 3D in vitro cell culture system, is highly similar to primary tissues and organs in vivo, and can recapitulate the phenotypic and genetic characteristics of target organs. Publications on cancer organoids have recently increased, and many types of cancer organoids have been used for modeling cancer processes, as well as for drug discovery and screening. On the basis of the current research status, more exploration of cancer organoids through technical advancements is required to improve reproducibility and scalability. Moreover, given the natural characteristics of organoids, greater attention must be paid to ethical considerations. Here, we summarize recent advances in cancer organoid biobanking research, encompassing rectal, gastric, pancreatic, breast, and glioblastoma cancers. Living cancer biobanks that contain cancerous tissues and matched organoids with different genetic backgrounds, subtypes, and individualized characteristics will eventually contribute to the understanding of cancer and ultimately facilitate the development of innovative treatments.

Recent Advance and Modification Strategies of Transition Metal Dichalcogenides (TMDs) in Aqueous Zinc Ion Batteries.

In recent years, aqueous zinc ion batteries (ZIBs) have attracted much attention due to their high safety, low cost, and environmental friendliness. Owing to the unique layered structure and more desirable layer spacing, transition metal dichalcogenide (TMD) materials are considered as the comparatively ideal cathode material of ZIBs which facilitate the intercalation/ deintercalation of hydrated Zn2+ between layers. However, some disadvantages limit their widespread application, such as low conductivity, low reversible capacity, and rapid capacity decline. In order to improve the electrochemical properties of TMDs, the corresponding modification methods for each TMDs material can be designed from the following modification strategies: defect engineering, intercalation engineering, hybrid engineering, phase engineering, and in-situ electrochemical oxidation. This paper summarizes the research progress of TMDs as cathode materials for ZIBs in recent years, discusses and compares the electrochemical properties of TMD materials, and classifies and introduces the modification methods of MoS2 and VS2. Meanwhile, the corresponding modification scheme is proposed to solve the problem of rapid capacity fading of WS2. Finally, the research prospect of other TMDs as cathodes for ZIBs is put forward.