Fast and efficient As(III) removal from water by bifunctional nZVI@NBC.

As a notable toxic substance, metalloid arsenic (As) widely exists in water body and drinking As-contaminated water for an extended period of time can result in serious health concerns. Here, the performance of nanoscale zero-valent iron (nZVI) modified N-doped biochar (NBC) composites (nZVI@NBC) activated peroxydisulfate (PDS) for As(III) removal was investigated. The removal efficiencies of As(III) with initial concentration ranging from 50 to 1000 µg/L were above 99% (the residual total arsenic below 10 µg/L, satisfying the contaminant limit for arsenic in drinking water) within 10 min by nZVI@NBC (0.2 g/L)/PDS (100 µM). As(III) removal efficiency influenced by reaction time, PDS dosage, initial concentration, pH, co-existing ions, and natural organic matter in nZVI@NBC/PDS system were investigated. The nZVI@NBC composite is magnetic and could be conveniently collected from aqueous solutions. In practical applications, nZVI@NBC/PDS has more than 99% As(III) removal efficiency in various water bodies (such as deionized water, piped water, river water, and lake water) under optimized operation parameters. Radical quenching and EPR analysis revealed that SO4·- and ·OH play important roles in nZVI@NBC/PDS system, and the possible reaction mechanism was further proposed. These results suggest that nZVI@NBC activated peroxydisulfate may be an efficient and fast approach for the removal of water contaminated with As(III).

Association analyses between the variants of SNAP25, SV2C and ST3GAL2 and the efficacy of botulinum toxin A in the treatment of the primary Meige syndrome.

Objective: Individual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25, SV2C and ST3GAL2, which are involving in the translocation of the BoNT-A in vivo. Methods: Patients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25, SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage. Results: Among the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms <30%). As to the duration of efficacy, 52 patients (50.0%) had a long duration of efficacy (≥4 months), and 52 (50.0%) had a short (<4 months). In terms of primary Meige syndrome, SNAP25 rs6104571 was found associating with the maximum improvement rate of motor symptoms (Genotype: P = 0.02, OR = 0.26; Allele: P = 0.013, OR = 0.29), and SV2C rs31244 was found associating with the duration of efficacy (Genotype: P = 0.024, OR = 0.13; Allele: P = 0.012, OR = 0.13). Besides, we also conducted the association analyses between the variants and BoNT-A-related adverse reactions. Although, there was no statistical difference between the allele of SV2C rs31244 and BoNT-A-related adverse reactions, there was a trend (P = 0.077, OR = 2.56). In the replication stage, we included 39 patients with primary cervical dystonia to further expanding the samples' size. Among the 39 primary cervical dystonia patients, 25 patients (64.1%) had a good efficacy (the maximum improvement rate of motor symptoms ≥50%) and 14 (35.9%) had a poor (the maximum improvement rate of motor symptoms <50%). As to the duration of efficacy, 32 patients (82.1%) had a long duration of efficacy (≥6 months), and 7 (17.9%) had a short (<6 months). Integrating primary Meige syndrome and primary cervical dystonia, SV2C rs31244 was still found associating with the duration of efficacy (Genotype: P = 0.002, OR = 0. 23; Allele: P = 0.001, OR = 0. 25). Conclusion: In our study, SNAP25 rs6104571 was associated with the maximum improvement rate of motor symptoms in patients with primary Meige syndrome treated with BoNT-A, and patients carrying this variant had a lower improvement rate of motor symptoms. SV2C rs31244 was associated with duration of treatment in patients with primary Meige syndrome treated with BoNT-A and patients carrying this variant had a shorter duration of treatment. Patients with primary Meige syndrome carrying SV2C rs31244 G allele have an increase likelihood of BoNT-A-related adverse reactions. Involving 39 patients with primary cervical dystonia, the results further verify that SV2C rs31244 was associated with duration of treatment and patients carrying this variant had a shorter duration of treatment.

Transport of nanoscale zero-valent iron in the presence of rhamnolipid.

Nanoscale zero-valent iron (nZVI) particles have gained widespread use for in-situ treatment of various chlorinated hydrocarbons. Their non-toxic nature, affordability, and minimal maintenance requirements have made them a favored material for nanoremediation. The treatment typically involves the injection of nZVI particles into contaminated sites using direct-push well injection systems. However, their small size leads to high surface energy, causing aggregation that alters their physiochemical properties, reactivity, and transport behavior. To counteract aggregation, nZVI suspension can be stabilized with different surfactants, reducing the surface energy during subsurface soil transport. This study investigates the impact of rhamnolipid, a biosurfactant produced by Pseudomonas aeruginosa during the late growth phase, on the aggregation and mobility of nZVI particles. The retardation factor of nZVI in the model media of zeolite, ZK406H, decreased from 1.66 in the absence of rhamnolipid to 1.03, 0.98, 0.93, and 0.87, corresponding to the presence of rhamnolipid at concentrations of 20, 50, 80, and 100 mg/L. The deposition coefficient also decreased from 2.39 in the absence of rhamnolipid to 0.459, 0.279, 0.217, and 0.0966, corresponding to the presence of rhamnolipid at concentrations of 20, 50, 80, and 100 mg/L. The transport parameters of nZVI in ZK406H were linked to the interactions of nZVI particles with ZK406H by the DLVO theory.

MOICS, a novel classier deciphering immune heterogeneity and aid precise management of clear cell renal cell carcinoma at multiomics level.

Recent studies have indicated that the tumor immune microenvironment plays a pivotal role in the initiation and progression of clear cell renal cell carcinoma (ccRCC). However, the characteristics and heterogeneity of tumor immunity in ccRCC, particularly at the multiomics level, remain poorly understood. We analyzed immune multiomics datasets to perform a consensus cluster analysis and validate the clustering results across multiple internal and external ccRCC datasets; and identified two distinctive immune phenotypes of ccRCC, which we named multiomics immune-based cancer subtype 1 (MOICS1) and subtype 2 (MOICS2). The former, MOICS1, is characterized by an immune-hot phenotype with poor clinical outcomes, marked by significant proliferation of CD4+ and CD8+ T cells, fibroblasts, and high levels of immune inhibitory signatures; the latter, MOICS2, exhibits an immune-cold phenotype with favorable clinical characteristics, characterized by robust immune activity and high infiltration of endothelial cells and immune stimulatory signatures. Besides, a significant negative correlation between immune infiltration and angiogenesis were identified. We further explored the mechanisms underlying these differences, revealing that negatively regulated endopeptidase activity, activated cornification, and neutrophil degranulation may promote an immune-deficient phenotype, whereas enhanced monocyte recruitment could ameliorate this deficiency. Additionally, significant differences were observed in the genomic landscapes between the subtypes: MOICS1 exhibited mutations in TTN, BAP1, SETD2, MTOR, MUC16, CSMD3, and AKAP9, while MOICS2 was characterized by notable alterations in the TGF-ß pathway. Overall, our work demonstrates that multi-immune omics remodeling analysis enhances the understanding of the immune heterogeneity in ccRCC and supports precise patient management.

A potential virulence factor: Brucella flagellin FliK does not affect the main biological properties but inhibits the inflammatory response in RAW264.7 cells.

The bacterial flagellum is an elongated filament that protrudes from the cell and is responsible for bacterial motility. It can also be a pathogen-associated molecular pattern (PAMP) that regulates the host immune response and is involved in bacterial pathogenicity. In contrast to motile bacteria, the Brucella flagellum does not serve a motile purpose. Instead, it plays a role in regulating Brucella virulence and the host's immune response, similar to other non-motile bacteria. The flagellin protein, FliK, plays a key role in assembly of the flagellum and also as a potential virulence factor involved in the regulation of bacterial virulence and pathogenicity. In this study, we generated a Brucella suis S2 flik gene deletion strain and its complemented strain and found that deletion of the flik gene has no significant effect on the main biological properties of Brucella, but significantly enhanced the inflammatory response induced by Brucella infection of RAW264.7 macrophages. Further experiments demonstrated that the FliK protein was able to inhibit LPS-induced cellular inflammatory responses by down-regulating the expression of MyD88 and NF-κB, and by decreasing p65 phosphorylation in the NF-κB pathway; it also inhibited the expression of NLRP3 and caspase-1 in the NLRP3 inflammasome pathway. In conclusion, our study suggests that Brucella FliK may act as a virulence factor involved in the regulation of Brucella pathogenicity and modulation of the host immune response.

Dehydrozaluzanin C- derivative protects septic mice by alleviating over-activated inflammatory response and promoting the phagocytosis of macrophages.

Host-directed therapy (HDT) is a new adjuvant strategy that interfere with host cell factors that are required by a pathogen for replication or persistence. In this study, we assessed the effect of dehydrozaluzanin C-derivative (DHZD), a modified compound from dehydrozaluzanin C (DHZC), as a potential HDT agent for severe infection. LPS-induced septic mouse model and Carbapenem resistant Klebsiella pneumoniae (CRKP) infection mouse model was used for testing in vivo. RAW264.7 cells, mouse primary macrophages, and DCs were used for in vitro experiments. Dexamethasone (DXM) was used as a positive control agent. DHZD ameliorated tissue damage (lung, kidney, and liver) and excessive inflammatory response induced by LPS or CRKP infection in mice. Also, DHZD improved the hypothermic symptoms of acute peritonitis induced by CRKP, inhibited heat-killed CRKP (HK-CRKP)-induced inflammatory response in macrophages, and upregulated the proportions of phagocytic cell types in lungs. In vitro data suggested that DHZD decreases LPS-stimulated expression of IL-6, TNF-α and MCP-1 via PI3K/Akt/p70S6K signaling pathway in macrophages. Interestingly, the combined treatment group of DXM and DHZD had a higher survival rate and lower level of IL-6 than those of the DXM-treated group; the combination of DHZD and DXM played a synergistic role in decreasing IL-6 secretion in sera. Moreover, the phagocytic receptor CD36 was increased by DHZD in macrophages, which was accompanied by increased bacterial phagocytosis in a clathrin- and actin-dependent manner. This data suggests that DHZD may be a potential drug candidate for treating bacterial infections.

Associations of residential greenness exposure and ambient air pollutants with newly-diagnosed drug-resistant tuberculosis cases.

Growing evidence has found the health protective effects of greenness exposure on tuberculosis (TB) and the impact of ambient air pollutants on TB drug-resistance. However, it remains unclear whether residential greenness is also beneficial to reduce TB drug-resistance, and whether air pollution modify the greenness-TB resistance relationship. We enrolled 5006 newly-diagnosed TB patients from Shandong, China, during 2014 to 2021. Normalized Difference Vegetation Index (NDVI) in 250 m and 500 m buffer around individuals' residential zone was used to assess greenness exposure. All patients were divided by quartiles of NDVI250-m and NDVI500-m (from low to high: Q1, Q2, Q3, Q4) respectively. Six logistic regression models (NDVI, NDVI + PM2.5/PM10/SO2/NO2/O3) were used to estimate the association of NDVI and TB drug-resistance when adjusting different air pollutants or not. All models were adjusted for age, gender, body mass index, complications, smoking, drinking, population density, nighttime light index, road density. Compared with participants in NDVI250-m Q1 and NDVI500-m Q1, other groups had lower rates of MDR-TB, PDR-TB, RFP-resistance, SM-resistance, RFP + SM resistance, INH + RFP + EMB + SM resistance. NDVI500-m reduced the risk of multidrug resistant tuberculosis (MDR-TB) and the adjusted odds ratio (aOR, 95% confidence interval, CI) compared with NDVI500-m Q1 were 0.736 (0.547-0.991) in NDVI + PM10 model, 0.733 (0.544-0.986) in NDVI + PM2.5 model, 0.735(0.546-0.99) in NDVI + SO2 model, 0.736 (0.546-0.991) in NDVI + NO2 model, respectively, P < 0.05. NDVI500-m contributed to a decreased risk of streptomycin (SM)-resistance. The aOR of rifampicin (RFP) + SM resistance were 0.132 (NDVI250-m, Q4 vs Q1, 95% CI: 0.03-0.578), 0.199 (NDVI500-m, Q3 vs. Q1, 95% CI: 0.057-0.688) and 0.264 (NDVI500-m, Q4 vs. Q1, 95% CI: 0.087-0.799). The adjusted ORs (Q2 vs. Q1, 95% CI) of isoniazid (INH) + RFP + ethambutol (EMB) + SM resistance in 500 m buffer were 0.276 (0.119-0.639) in NDVI model, 0.279 (0.11-0.705) in NDVI + PM10 model, 0.281 (0.111-0.713) in NDVI + PM2.5 model, 0.279 (0.11-0.709) in NDVI + SO2 model, 0.296 (0.117-0.754) in NDVI + NO2 model, 0.294 (0.116-0.748) in NDVI + O3 model, respectively. The study showed, for the first time, that residential greenness exposure in 500 m buffer is beneficial for reducing newly-diagnosed DR-TB (including PDR-RB, MDR-TB, MR-TB), and ambient air pollutants may partially mediate this association.

Inhibition of lysyl oxidase by pharmacological intervention and genetic manipulation alleviates epilepsy-associated cognitive disorder.

Epilepsy-associated cognitive disorder (ECD), a prevalent comorbidity in epilepsy patients, has so far uncharacterized etiological origins. Our prior work revealed that lysyl oxidase (Lox) acted as a novel contributor of ferroptosis, a recently discovered cell death mode in the regulation of brain function. However, the role of Lox-mediated ferroptosis in ECD remains unknown. ECD mouse model was established 2 months later following a single injection of kainic acid (KA) for. After chronic treatment with KA, mice were treated with different doses (30 mg/kg, 100 mg/kg and 300 mg/kg) of Lox inhibitor BAPN. Additionally, hippocampal-specific Lox knockout mice was also constructed and employed to validate the role of Lox in ECD. Cognitive functions were assessed using novel object recognition test (NOR) and Morris water maze test (MWM). Protein expression of phosphorylated cAMP-response element binding (CREB), a well-known molecular marker for evaluation of cognitive performance, was also detected by Western blot. The protein distribution of Lox was analyzed by immunofluorescence. In KA-induced ECD mouse model, ferroptosis process was activated according to upregulation of 4-HNE protein and a previously discovered ferroptosis in our group, namely, Lox was remarkably increased. Pharmacological inhibition of Lox by BAPN at the dose of 100 mg/kg significantly increased the discrimination index following NOR test and decreased escape latency as well as augmented passing times within 60 s following MWM test in ECD mouse model. Additionally, deficiency of Lox in hippocampus also led to pronounced improvement of deficits in ECD model. These findings indicate that the ferroptosis regulatory factor, Lox, is activated in ECD. Ablation of Lox by either pharmacological intervention or genetic manipulation ameliorates the impairment in ECD mouse model, which suggest that Lox serves as a promising therapeutic target for treating ECD in clinic.

A numerical study on the siphonic effect of enhanced external counterpulsation at lower extremities with a coupled 0D-1D closed-loop personalized hemodynamics model.

Enhanced external counterpulsation (EECP) is a treatment and rehabilitation approach for ischemic diseases, including coronary artery disease. Its therapeutic benefits are primarily attributed to the improved blood circulation achieved through sequential mechanical compression of the lower extremities. However, despite the crucial role that hemodynamic effects in the lower extremity arteries play in determining the effectiveness of EECP treatment, most studies have focused on the diastole phase and ignored the systolic phase. In the present study, a novel siphon model (SM) was developed to investigate the interdependence of several hemodynamic parameters, including pulse wave velocity, femoral flow rate, the operation pressure of cuffs, and the mean blood flow changes in the femoral artery throughout EECP therapy. To verify the accuracy of the SM, we coupled the predicted afterload in the lower extremity arteries during deflation using SM with the 0D-1D patient-specific model. Finally, the simulation results were compared with clinical measurements obtained during EECP therapy to verify the applicability and accuracy of the SM, as well as the coupling method. The precision and reliability of the previously developed personalized approach were further affirmed in this study. The average waveform similarity coefficient between the simulation results and the clinical measurements during the rest state exceeded 90%. This work has the potential to enhance our understanding of the hemodynamic mechanisms involved in EECP treatment and provide valuable insights for clinical decision-making.

Proteinaceous Microsphere-Based Water-in-Oil Pickering Emulsions for Preservation of Chlorella Cells.

Microalgae are highly regarded as ideal materials for the creation of liquid biofuels and have substantial potential for growth and utilization. However, traditional storage and culture methods for microalgae are plagued by challenges such as uncontrolled growth, bacterial contamination, and self-shading among algae. These issues severely impede the photosynthetic process and the efficient extraction of biomass energy. This study tackles these problems by utilizing magnetic hydrophobic protein particles to stabilize water-in-oil Pickering emulsions. This allows for the micro-compartment storage and magnetic transfer of algae. Additionally, the successful encapsulation of Chlorella cells in high-internal-phase water-in-oil Pickering emulsions effectively mitigates the settling problem of Chlorella cells in the liquid phase, thereby enabling the potential use of Pickering emulsions for the confined cultivation of microalgae.

A Directed Evolution Protocol for Engineering Minimal Transcription Factors, Based on CIS Display.

Directed evolution is an efficient strategy for obtaining desired biomolecules. Since the 1990s, the emergence of display techniques has enabled high-throughput screening of functional proteins. However, classical methods require library construction by plasmid cloning and are limited by transformation efficiencies, typically limiting library sizes to ~106-107 variants. More recently, in vitro techniques have emerged that avoid cloning, allowing library sizes of >1012 members. One of these, CIS display, is a DNA-based display technique which allows high-throughput selection of biomolecules in vitro. CIS display creates the genotype-phenotype link required for selection by a DNA replication initiator protein, RepA, that binds exclusively to the template from which it has been expressed. This method has been successfully used to evolve new protein-protein interactions but has not been used before to select DNA-binding proteins, which are major components in mammalian synthetic biology. In this chapter, we describe a directed evolution method using CIS display to efficiently select functional DNA-binding proteins from pools of nonbinding proteins. The method is illustrated by enriching the minimal transcription factor Cro from a low starting frequency (1 in 109). This protocol is also applicable to engineering other DNA-binding proteins or transcription factors from combinatorial libraries.

Gastrin-releasing peptide receptor (GRPR) as a novel biomarker and therapeutic target in prostate cancer.

Aim: This comprehensive review aims to explore the potential applications of Gastrin-releasing peptide receptor (GRPR) in the diagnosis and treatment of prostate cancer. Additionally, the study investigates the role of GRPR in prognostic assessment for individuals afflicted with prostate cancer.Methods: The review encompasses a thorough examination of existing literature and research studies related to the upregulation of GRPR in various tumor types, with a specific focus on prostate. The review also evaluates the utility of GRPR as a molecular target in prostate cancer research, comparing its significance to the well-established Prostate-specific membrane antigen (PSMA). The integration of radionuclide-targeted therapy with GRPR antagonists is explored as an innovative therapeutic approach for individuals with prostate cancer.Results: Research findings suggest that GRPR serves as a promising molecular target for visualizing low-grade prostate cancer. Furthermore, it is demonstrated to complement the detection of lesions that may be negative for PSMA. The integration of radionuclide-targeted therapy with GRPR antagonists presents a novel therapeutic paradigm, offering potential benefits for individuals undergoing treatment for prostate cancer.Conclusions: In conclusion, this review highlights the emerging role of GRPR in prostate cancer diagnosis and treatment. Moreover, the integration of radionuclide-targeted therapy with GRPR antagonists introduces an innovative therapeutic approach that holds promise for improving outcomes in individuals dealing with prostate cancer. The potential prognostic value of GRPR in assessing the disease's progression adds another dimension to its clinical significance in the realm of urology.

Construction of Ge-Stereogenic Center by Desymmetric Carbene Insertion of Dihydrogermanes.

We developed a method for the enantioselective synthesis of germanium-stereogenic compounds by the desymmetric carbene insertion of dihydrogermanes. A chiral rhodium phosphate catalyst decomposes diaryldiazo-methanes to generate rhodium carbenes that insert enantioselectively into one of the two Ge-H bonds of dihydrogermanes to form germanium-stereogenic compounds under mild reaction conditions. By this method, a variety of chiral germanes with germanium-stereogenic centers were synthesized in high yields and excellent enantioselectivities. Kinetic studies of the reaction showed that the diazo decomposition process was the rate-determining step. The remaining Ge-H bond of the chiral germane products provides a possibility for preparing chiral tetra-substituted germanium-stereogenic compounds.

Myosin in autoinhibited off state(s), stabilized by mavacamten, can be recruited in response to inotropic interventions.

Mavacamten is a FDA-approved small-molecule therapeutic designed to regulate cardiac function at the sarcomere level by selectively but reversibly inhibiting the enzymatic activity of myosin. It shifts myosin toward ordered off states close to the thick filament backbone. It remains elusive whether these myosin heads in the off state(s) can be recruited in response to physiological stimuli when required to boost cardiac output. We show that cardiac myosins stabilized in these off state(s) by mavacamten are recruitable by 1) Ca2+, 2) increased chronotropy [heart rate (HR)], 3) stretch, and 4) ß-adrenergic (ß-AR) stimulation, all known physiological inotropic interventions. At the molecular level, we show that Ca2+ increases myosin ATPase activity by shifting mavacamten-stabilized myosin heads from the inactive super-relaxed state to the active disordered relaxed state. At the myofilament level, both Ca2+ and passive lengthening can shift mavacamten-ordered off myosin heads from positions close to the thick filament backbone to disordered on states closer to the thin filaments. In isolated rat cardiomyocytes, increased stimulation rates enhanced shortening fraction in mavacamten-treated cells. This observation was confirmed in vivo in telemetered rats, where left-ventricular dP/dtmax, an index of inotropy, increased with HR in mavacamten-treated animals. Finally, we show that ß-AR stimulation in vivo increases left-ventricular function and stroke volume in the setting of mavacamten. Our data demonstrate that the mavacamten-promoted off states of myosin in the thick filament are at least partially activable, thus preserving cardiac reserve mechanisms.

Structurally diverse cucurbitane-type triterpenoids from the tubers of Hemsleya chinensis with cytotoxic activity.

Ten previously undescribed cucurbitane-type triterpenoids, namely hemslyencins A-F (1-6) and hemslyencosides A-D (7-10), together with twenty previously reported compounds (11-30), were isolated from the tubers of Hemsleya chinensis. Their structures were elucidated by unambiguous spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR data). Hemslyencins A and B (1 and 2) possessing unique 9, 11-seco-ring system with a six-membered lactone moiety, were the first examples among of the cucurbitane-type triterpenoids, and hemslyencins C and D (3 and 4) and hemslyencoside D (10) are the infrequent pentacyclic cucurbitane triterpenes featuring a 6/6/6/5/6 fused system. The cytotoxic activities of all isolated compounds were evaluated against MCF-7, HCT-116, HeLa, and HepG2 cancer cells, and their structure-activity relationships (SARs) was discussed as well. Compounds 17, 25, and 26 showed significant cytotoxic effects with IC50 values ranging from 1.31 to 9.89 µM, among which compound 25 induced both apoptosis and cell cycle arrest at G2/M phase in a dose dependent manner against MCF-7 cells.

New solution for predicting the removal efficiency of organic contaminants by UV/ H2O2: From a case study of 1H-benzotriazole.

Rapid prediction of the removal efficiency and energy consumption of organic contaminants under various operating conditions is crucial for advanced oxidation processes (AOPs) in industrial application. In this study, 1H-Benzotriazole (BTZ, CAS: 95-14-7) is selected as a model micropollutant, a validated incorporated Computational Fluid Dynamics (CFD) model is employed to comprehensively investigate the impacts of initial concentrations of H2O2, BTZ and dissolved organic carbon (DOC) (i.e., [DOC]0, [BTZ]0 and [DOC]0), as well as the effective UV lamp power P and volumetric flow rate Qv. Generally, the operation performance depends on [DOC]0 and [BTZ]0 in similar trends, but with quantitatively different ways. The increase in [H2O2]0 and P/Qv can promote •OH generation, leading to the elimination of BTZ. It is worth noting that P/Qv is found to be linearly correlated with the removal order of BTZ (ROBTZ) under specific conditions. Based on this finding, the degradation of other potential organic contaminants with a wide range of rate constants by UV/H2O2 is further investigated. A model for predicting energy consumption for target removal rates of organic pollutants is established from massive simulation data for the first time. Additionally, a handy Matlab app is first developed for convenient application in water treatment. This work proposes a new operable solution for fast predicting operation performance and energy consumption for the removal of organic contaminants in industrial applications of advanced oxidation processes.

De novo transcriptome assembly and molecular response mechanism analysis of a diatom Cyclotella meneghiniana Kützing exposed to cadmium.

Cadmium is a persistent heavy metal commonly found in aquatic ecosystems and has a strong toxic effect on organisms. The sensitivity of phytoplankton to environmental changes and its role as an indicator of aquatic ecosystem health have been well-established. However, the mechanisms by which phytoplankton respond to cadmium remain incompletely understood. In this study, we chose the typical planktonic diatom Cyclotella meneghiniana Kützing, by integrating physiological-biochemical data and transcriptome analysis, to reveal the molecular mechanisms of C. meneghiniana responing to cadmium. Under cadmium stress, the cell density and chlorophyll-a content of C. meneghiniana significantly decreased, while MDA content and SOD activity gradually increased. At 72 h of cadmium stress, we found that at this time point, cell abundance and physiological variation were very significant, therefore we selected 72 h for subsequent analysis. To better understand the cadmium stress response mechanisms of C. meneghiniana, a de novo transcriptome method was used to analyse C. meneghiniana under cadmium stress for 72 h, and 1704 (M vs. CK) and 4788 (H vs. CK) differentially expressed genes were found. Our results showed that the changes in gene expression were closely correlated to the physiological-biochemical changes. Although cadmium stress could promote the nitrogen metabolism pathway, ROS scavenging system, and photosynthesis. While, C. meneghiniana under medium and high concentrations of cadmium can also limit various intracellular metabolic pathways, such as the MAPK pathway and phosphatidylinositol metabolic pathway, and the degree of inhibition increases with the increase of stress concentration. In present study, the complete molecular mechanism of the planktonic diatom response to cadmium has been established, which provided important information for further studies on heavy metal pollutants and the multiple functional genes responsible for cadmium sensitivity and tolerance in planktonic diatoms.

Dual-energy CT-based radiomics in predicting EGFR mutation status non-invasively in lung adenocarcinoma.

Objectives: Patients with epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma (LUAD) can benefit from individualized targeted therapy. This study aims to develop, compare, analyse prediction models based on dual-energy spectral computed tomography (DESCT) and CT-based radiomic features to non-invasively predict EGFR mutation status in LUAD. Materials and methods: Patients with LUAD (n = 175), including 111 patients with and 64 patients without EGFR mutations, were enrolled in the current study. All patients were randomly divided into a training dataset (122 cases) and validation dataset (53 cases) at a ratio of 7:3. After extracting CT-based radiomic, DESCT and clinical features, we built seven prediction models and a nomogram of the best prediction. Receiver operating characteristic (ROC) curves and the mean area under the curve (AUC) values were used for comparisons among the models to obtain the best prediction model for predicting EGFR mutations. Results: The best distinguishing ability is the combined model incorporating radiomic, DESCT and clinical features for predicting the EGFR mutation status with an AUC of 0.86 (95 % CI: 0.79-0.92) in the training group and an AUC value of 0.83 (95 % CI: 0.73, 0.96) in the validation group. Conclusions: Our study provides a predictive nomogram non-invasively with a combination of CT-based radiomic, DESCT and clinical features, which can provide image-based biological information for targeted therapy of LUAD with EGFR mutations.

Lower serum AMH concentration is correlated with serum IgG1 decreased in the infertile woman: A real-world retrospective study.

OBJECTIVES: In this real-world approach, we examined the serum Anti-Mullerian Hormone (AMH) level and the relationship with serum IgG subclass in the infertile women. METHODS: A total of 574 female participants were recruited for this study. The serum AMH, IgG subclass(IgG1, IgG2, IgG3, IgG4) and immunoglobulin (Ig) G、IgM、IgA、IgE as well as complement C3, C4 were analyzed. The difference in serum AMH level was assessed according categorized as above or below the median of the ratio of serum IgG subclass(IgG1, IgG2, IgG3, IgG4) to total IgG (RIgG subclass/IgG). RESULTS: The serum AMH level of the low RIgG1/IgG group is significantly decreased than that high RIgG1/IgG group (p < 0.05). The Spearman correlation analysis showed that the serum AMH level was significantly negatively correlated with age and significantly positively correlated with serum IgG1 levels respectively (p < 0.05). GLMMs multivariate model showed that after adjusting the covariate and possible mixed factors including age, serum immunoglobulin, complement C3 and C4, the serum AMH level was significantly positively correlated with IgG1 level (p < 0.01). CONCLUSIONS: Decreased serum IgG1 may significantly affect the ovarian reserve function of women. Confirmation of this association and elucidation of its underlying mechanisms are needed to place these results in a clinical perspective.

A self-assembling peptide inhibits the growth and function of fungi via a wrapping strategy.

Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and in situ form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC50 = 3.5 µM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 µM, better than fluconazole (17.2% at 1 µM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection.