Ni-P-PTFE cathode with low surface energy for enhancing electrochemical water softening performance.

Efficient cathode regeneration is a significant challenge in the electrochemical water softening process. This work explores the use of an electroless plating Ni-P-PTFE electrode with low surface energy for this purpose. The Ni-P-PTFE electrode demonstrates improved self-cleaning performance at high current densities. By combining the low surface energy of the electrode with fluid flushing shear force, the precipitation rate on the Ni-P-PTFE electrode remains stable at approximately 18 g/m2·h over extended periods of operation. Additionally, the cleaning efficiency of the Ni-P-PTFE electrode surpasses that of stainless steel by 66.34%. The Ni-P-PTFE electrode can maintain a larger active area and a longer operational lifespan is attributed to its self-cleaning performance derived from low surface energy. Furthermore, the loose scale layers on the electrode surface are easily removed during electrochemical water softening processes, presenting a novel approach to cathode surface design.

Rice N-biofertilization by inoculation with an engineered photosynthetic diazotroph.

Photosynthetic diazotrophs expressing iron-only (Fe-only) nitrogenase can be developed into a promising biofertilizer, as it is independent on the molybdenum availability in the soil. However, the expression of Fe-only nitrogenase in diazotrophs is repressed by the fixed nitrogen of the soil, limiting the efficiency of nitrogen fixation in farmland with low ammonium concentrations that are inadequate for sustainable crop growth. Here, we succeeded in constitutively expressing the Fe-only nitrogenase even in the presence of ammonium by controlling the transcription of Fe-only nitrogenase gene cluster (anfHDGK) with the transcriptional activator of Mo nitrogenase (NifA*) in several different ways, indicating that the engineered NifA* strains can be used as promising chassis cells for efficient expression of different types of nitrogenases. When applied as a biofertilizer, the engineered Rhodopseudomonas palustris effectively stimulated rice growth, contributing to the reduced use of chemical fertilizer and the development of sustainable agriculture.

Superiority of polatuzumab vedotin over other novel agents in previously untreated ABC-type diffuse large B-cell lymphoma: a network meta-analysis of 20 RCTs.

Because of lacking of head-to-head comparison among polatuzumab (Pola) vedotin and other novel agents for untreated diffuse large B-cell lymphoma (DLBCL), the optimal option remains undefined. We searched twelve relevant published reports, covering 8376 subjects. Interestingly, the PFS benefit with Pola-R-CHP over other regimens was found prominently in those B-cell-like type (ABC-type) patients. For those ABC-type patients, the PFS advantage with Pola-R-CHP was statistically significant, when compared to R-CHOP+Bort (HR: 0.52, P=0.02), R-CHOP+Ibru (HR: 0.43, P=0.001), R-CHOP+Lena (HR: 0.51, P=0.009), G-CHOP (HR: 0.46, P=0.008), and R-CHOP (HR: 0.40, P<0.001). Meanwhile, for those germinal center B-cell-like (GCB) type patients, no PFS advantage with Pola-R-CHP was found when compared to R-CHOP+Bort (HR: 1.18, P=0.46), R-CHOP+Lena (HR: 1.21, P=0.45), G-CHOP (HR: 1.39, P=0.14), R-CHOP-14 (HR: 0.94, P=0.82), and R-CHOP (HR: 1.00, P=1). The PFS advantage with Pola-R-CHP over other regimens might be confined to those patients of ABC-type DLBCL.

Superiority of ibrutinib plus bendamustine and rituximab in newly diagnosed patients with mantle-cell lymphoma ineligible for intensive therapy: A network meta-analysis.

Because of lacking of head-to-head comparison among recently effective novel agents' combination regimens for newly diagnosed patients with mantle-cell lymphoma (MCL) who are ineligible for intensive therapy like autologous stem-cell transplantation, the optimal option for these patients still remains undefined. We searched relevant published reports. Three randomized controlled trials with 1459 subjects were identified. In the network meta-analysis, ibrutinib plus bendamustine and rituximab (Ibru + BR) significantly improved progression-free survival (PFS) when compared to bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP; hazard ratio [HR]: 0.55, p = .03) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; HR: 0.35, p < .001) for newly diagnosed patients with MCL ineligible for intensive therapy. Among these first-line treatment regimens (Ibru + BR, VR-CAP, R-CHOP, and BR), Ibru + BR had the highest probability of 94.9% to be the best intervention in PFS analysis. No significant difference was found in adverse events analysis. Our data indicated that Ibru + BR seemed to prolong the PFS when compared to VR-CAP and R-CHOP for newly diagnosed patients with MCL ineligible for intensive therapy. Considering our limits, prospective clinical trials directly comparing these regimens are warranted.

Boron Bifunctional Catalysts for Rapid Degradation of Persistent Organic Pollutants in a Metal-Free Electro-Fenton Process: O2 and H2O2 Activation Process.

Metals usually served as the active sites of the heterogeneous bifunctional electro-Fenton reaction, which faced the challenge of poor stability under acidic or even neutral conditions. Exploring a metal-free heterogeneous bifunctional electro-Fenton catalyst can effectively solve the above problems. In this work, a stable metal-free heterogeneous bifunctional boron-modified porous carbon catalyst (BTA-1000) was synthesized. For the BTA-1000 catalyst, the yield of H2O2 (294 mg/L) significantly increased. The degradation rate of phenol by BTA-1000 (0.242 min-1) increased by an order of magnitude, compared with the porous carbon catalyst (0.0105 min-1). The BTA catalyst could rapidly degrade industrial dye wastewater, and its specific energy consumption was 5.52 kW h kg-1 COD-1, lower than that in previous reports (6.38-7.4 kW h kg-1 COD-1). DFT and XPS revealed that C═O and -BC2O groups jointly promoted the generation of H2O2, and the -BCO2 group played dominant roles in the generation of •OH because the oxygen atom near the electron-giving groups (-BCO2 group) facilitated the formation of hydrogen bond and H2O2 adsorption. This work gained deep insights into the reaction mechanism of the boron-modified porous carbon catalyst, which helped to guide the development of metal-free heterogeneous bifunctional electro-Fenton catalysts.

Set-regression with applications to subgroup analysis.

Regression is a commonly used statistical model. It is the conditional mean of the response given covariates µ(x)=E(Y|X=x) . However, in some practical problems, the interest is the conditional mean of the response given the covariates belonging to some set A. Notably, in precision medicine and subgroup analysis in clinical trials, the aim is to identify subjects who benefit the most from the treatment, or identify an optimal set in the covariate space which manifests treatment favoritism if a subject's covariates fall in this set and the subject is classified to the favorable treatment subgroup. Existing methods for subgroup analysis achieve this indirectly by using classical regression. This motivates us to develop a new type of regression: set-regression, defined as µ(A)=E(Y|X∈A) which directly addresses the subgroup analysis problem. This extends not only the classical regression model but also improves recursive partitioning and support vector machine approaches, and is particularly suitable for objectives involving optimization of the regression over sets, such as subgroup analysis. We show that the new versatile set-regression identifies the subgroup with increased accuracy. It is easy to use. Simulation studies also show superior performance of the proposed method in finite samples.

An Investigation of the Anti-Depressive Properties of Phenylpropanoids and Flavonoids in Hemerocallis citrina Baroni.

The World Health Organization predicts that over the next several years, depression will become the most important mental health issue globally. Growing evidence shows that the flower buds of Hemerocallis citrina Baroni (H. citrina) possess antidepressant properties. In the search for new anti-depression drugs, a total of 15 phenylpropanoids and 22 flavonoids were isolated and identified based on spectral data (1D and 2D NMR, HR-ESI-MS, UV) from H. citrina. Among them, compound 8 was a novel compound, while compounds 1-4, 6, 9, 10, 15, 17, 24-26, 28, and 37 were isolated for the first time from Hemerocallis genus. To study the antidepressant activity of phenylpropanoids and flavonoids fractions from H. citrina, macroporous resin was used to enrich them under the guidance of UV characteristics. UHPLC-MS/MS was applied to identify the constituents of the enriched fractions. According to behavioral tests and biochemical analyses, it showed that phenylpropanoid and flavonoid fractions from H. citrina can improve the depressive-like mental state of chronic unpredictable mild stress (CUMS) rats. This might be accomplished by controlling the amounts of the inflammatory proteins IL-6, IL-1ß, and TNF-α in the hippocampus as well as corticosterone in the serum. Thus, the monomer compounds were tested for their anti-neuroinflammatory activity and their structure-activity relationship was discussed in further detail.

An innovative compound bed of EDI device with enhancing ion-exchange resins regeneration efficiency.

Electrodeionization (EDI) technology is limited by low regeneration efficiency of ion exchange resins, requirements of high-quality influent water, fouling of the ion exchange membrane and electrode, etc. In this work, a novel bed type called a compound bed in which cation and anion exchange resins were near the cation and anion exchange membrane and placed in layers, was proposed to implement high-efficiency regeneration of ion exchange resins. The influence of different operating conditions on the regeneration efficiency of ion exchange resins was elucidated as well. The regeneration efficiency of ion exchange resins could reach 73.1%, when the device was operated for 5 h under current density of 9 mA/cm2, with a cation and anion exchange resins ratio of 2: 3, influent water conductivity of 1,360 µS/cm and hardness of 400 mg/L. Therefore, the proposed compound bed structure not only widened the inlet water conditions, but also achieved the high-efficiency regeneration of ion exchange resins and anti-fouling of membranes and electrodes.

Carfilzomib-containing combinations as frontline therapy for multiple myeloma: A meta-analysis of 13 trials.

OBJECTIVE: To investigate the activity and safety of carfilzomib-containing combinations as frontline therapy for multiple myeloma. METHODS: We searched published carfilzomib reports for newly diagnosed multiple myeloma. RESULTS: Thirteen trials were identified, covering 704 subjects. Pooled analysis showed that carfilzomib combinations as frontline therapy for multiple myeloma attained an impressive at least complete response (≥CR) rate of 21%, at least very good partial response (≥VGPR) rate of 68%, overall response rate (ORR) of 94%. The ≥CR rates of 18% pre-SCT were increased to 43% of post-ASCT, and 64% of postconsolidation (P<.001). For those patients receiving carfilzomib therapy, response quality improved further over time (≥CR rates of 10% after 2nd cycle, 20% after 4th cycle, 43% after 8th cycle; ≥VGPR of 29% after 2nd cycle, 68% after 4th cycle, 88% after 8th cycle). ≥CR rates of 49% from CFZ-LEN-DEX triplet regimen were higher than 18% from CFZ-CYC-DEX triplet regimen and 21% from CFZ-THA-DEX triplet regimen (P=.03). CONCLUSIONS: Carfilzomib combinations could produce clinical benefits in newly diagnosed patients with multiple myeloma. High-quality response rate could be further improved through ASCT, consolidation therapy, and more cycles of chemotherapy even in the era of carfilzomib. CFZ-LEN-DEX could be a good combination regimen.

Self-phosphorylating deoxyribozyme initiated cascade enzymatic amplification for guanosine-5'-triphosphate detection.

The self-phosphorylating deoxyribozymes identified by in vitro selection can catalyze their own phosphorylation by utilizing phosphate donor guanosine-5'-triphosphate (GTP) which plays a critical role in a majority of cellular processes. On the basis of the unique properties of self-phosphorylating deoxyribozymes, we report a novel GTP sensor coupled with λ exonuclease cleavage reaction and nicking enzyme assisted fluorescence signal amplification process. The deoxyribozymes with special catalytic and structural characteristics display good stability compared to protein and RNA enzymes. We combined these properties with enzymatic recycling cleavage strategy to build a sensor which produced enhanced fluorescence signal. Sensitive and selective detection of GTP was successfully realized with the well-designed deoxyribozyme-based sensing platform by taking advantage of the self-phosphorylating ability of the kinase deoxyribozyme, efficient digestion capacity of λ exonuclease, and enzymatic recycling amplification of nicking enzyme. The method not only provides a platform for detecting GTP but also shows great potential in analyzing a variety of targets by combining deoxyribozymes with signal amplification strategy.

Multiresponsive rolling circle amplification for DNA logic gates mediated by endonuclease.

Rolling circle amplification (RCA), an efficient isothermal amplification method allowing the polymerase-mediated generation of long single-stranded DNA molecules made of tandem repeats, has been widely used in biomedical and nanotechnology fields due to structural and compositional versatility of its components. In this work, we confer multiresponsiveness to RCA reactions by designing dumbbell-shaped DNA templates and hairpin probes containing different endonuclease cleavage sites. Endonucleases trigger the release of RCA primers or the cleavage of DNA templates, which controls subsequent RCA reactions. A set of one-input and two-input DNA logic gates, which use endonucleases or hairpin probes as inputs, including YES, NOT, AND, OR, NOR, and INHIBIT, are constructed on the basis of our proposed multiresponsive RCA reactions. We demonstrate flexibility and scalability of these logic gates by integrating them to fabricate more complex three-input logic circuits (AND-OR and NOR-AND circuits). Moreover, our strategy is used to construct an assay system for endonuclease activity. Our proposed method might be applicable in the multichannel detection of endonucleases, nucleic acids, and other biomolecules.

Arrest of rolling circle amplification by protein-binding DNA aptamers.

Certain DNA polymerases, such as ϕ29 DNA polymerase, can isothermally copy the sequence of a circular template round by round in a process known as rolling circle amplification (RCA), which results in super-long single-stranded (ss) DNA molecules made of tandem repeats. The power of RCA reflects the high processivity and the strand-displacement ability of these polymerases. In this work, the ability of Ï•29DNAP to carry out RCA over circular templates containing a protein-binding DNA aptamer sequence was investigated. It was found that protein-aptamer interactions can prevent this DNA polymerase from reading through the aptameric domain. This finding indicates that protein-binding DNA aptamers can form highly stable complexes with their targets in solution. This novel observation was exploited by translating RCA arrest into a simple and convenient colorimetric assay for the detection of specific protein targets, which continues to showcase the versatility of aptamers as molecular recognition elements for biosensing applications.

Comparison of venetoclax and ivosidenib/enasidenib for unfit newly diagnosed patients with acute myeloid leukemia and IDH1/2 mutation: a network meta-analysis.

Because of lacking of head-to-head comparison between venetoclax and IDH1/IDH2 inhibitors (ivosidenib/enasidenib) for newly diagnosed unfit patients with acute myeloid leukemia (AML), the optimal option for these patients still remains undefined. We searched relevant published reports. Three RCTs with 180 IDH1 mutant and 165 IDH2 mutant patients were identified. Indirect comparison of OS using fixed effects network meta-analysis (NMA) models indicated venetoclax plus azacitidine (Ven-Aza) significantly improved survival than enasidenib plus azacitidine (Ena-Aza) (HR:0.30, p = 0.005) for those newly diagnosed patients with AML and IDH2 Mutation. And, for those IDH2 mutation patients, Ven-Aza also had the highest probability of 98.3% (OS analysis) and 84.0% (CR/CRi analysis) to be the best intervention among these first-line treatment regimens (Ven-Aza, Ena-Aza and Aza). And, there was a favorable trend towards Ven-Aza in survival analysis (HR:0.69, p = 0.42), when compared to ivosidenib plus azacitidine (Ivo-Aza) for those newly diagnosed patients with AML and IDH1 Mutation. For those IDH1 Mutation, venetoclax plus azacitidine (Ven-Aza) had the highest probability of 65.8% (OS analysis) and 73.0% (CR/CRi analysis) to be the best intervention among these first-line treatment regimens (Ven-Aza, ivosidenib plus azacitidine (Ivo-Aza) and azacitidine (Aza)). In conclusion, venetoclax plus azacitidine could be a good option for unfit newly diagnosed patients with acute myeloid leukemia and IDH1/2 mutation. Considering our limits (only trial data-based network meta-analysis et al.), future trials directly comparing these regimens are warranted.

Research on reliability index and failure probability of inherent defect insurance from the insurance perspective.

With the continuous improvement of people 's living standards, people have put forward higher requirements for the safety and comfort of housing. Therefore, Inherent Defect Insurance, a financial method to guarantee the quality of construction projects, has also emerged. At present, China 's Inherent Defect Insurance has been gradually promoted, but its claim mechanism has not been analyzed and studied. From the perspective of construction engineering, this paper first makes a bibliometric analysis of the influencing factors of insurance claims that may be caused by construction engineering quality through VOSViewers, and the evaluation index system of inherent defects is constructed. Then, according to the influencing factors, the PSO-LSSVR model is adopted to fit the performance function of the inherent defects. Finally, based on the reliability design principle of engineering structure, the reliability index and failure probability of Inherent Defect Insurance are derived from the performance function of inherent defects. This paper also analyzes its application in insurance practice and determines the relationship between the number of insurance underwriting policies and the initial reserve of insurance at a certain risk level. This paper studies the probability of Inherent Defect Insurance by constructing the reliability model of inherent defect risks in construction quality, and analyzes the anti-risk ability of insurance companies from the perspective of claim, which provides scientific analysis methods and theoretical basis for the scientific decision-making of insurance companies.

Bioinspired Sulfobetaine Borneol Fluorinated Amphiphilic Polymers for Marine Antifouling and Fouling Release Applications.

The development of nontoxic antifouling coatings in static marine environments is urgent. Herein, the successful synthesis of sulfobetaine borneol fluorinated polymers (PEASBF) by a free radical polymerization method is reported. The PEASBF coatings exhibit outstanding antifouling activity, which effectively resists the adhesion of Bovine serum albumin (FITC-BSA adhesion rate: 0.5%), Pseudomonas sp. (Biofilm: 1.3 absorbance) and Navicula sp. (Diatom attachment rate: 33%). More importantly, the PEASBF coatings display outstanding fouling release properties, achieving a release rate of 98% for Navicula sp., and the absorbance of the Pseudomonas sp. biofilm is only 0.2 under 10 Pa shear stress. XPS and MD studies showed that the fluorinated/isobornyl groups induce more sulfobetaine groups to migrate toward polymer surfaces for intensify antifouling. Additionally, the chiral stereochemical structure of borneol enhances antifouling and fouling release ability of amphiphilic polymers. Therefore, the PEASBF has the potential for static marine antifouling applications.

Impact of earthworms on antibiotic resistance genes removal in ampicillin-contaminated soil through bacterial community alteration.

The emergence of antibiotic resistance genes (ARGs) as contaminants in soil poses a significant threat to public health. Earthworms (Eisenia foetida), which are common inhabitants of soil, have been extensively studied for their influence on ARGs. However, the specific impact of earthworms on penicillin-related ARGs remains unclear. In this study, we investigate the role of earthworms in mitigating ARGs, specifically penicillin-related ARGs, in ampicillin-contaminated soil. Utilizing high-throughput quantitative PCR (HT-qPCR), we quantified a significant reduction in the relative abundance of penicillin-related ARGs in soil treated with earthworms, showing a decrease with a p-value of <0.01. Furthermore, high-throughput 16S rRNA gene sequencing revealed that earthworm intervention markedly alters the microbial community structure, notably enhancing the prevalence of specific bacterial phyla such as Proteobacteria, Firmicutes, Chloroflexi, and Tenericutes. Our findings not only demonstrate the effectiveness of earthworms in reducing the environmental load of penicillin-related ARGs but also provide insight into the alteration of microbial communities as a potential mechanism. This research contributes to our understanding of the role of earthworms in mitigating the spread of antibiotic resistance and provides valuable insights for the development of strategies to combat this global health issue.

Interpretable GWAS by linking clinical phenotypes to quantifiable immune repertoire components.

Bridging the gap between genotype and phenotype in GWAS studies is challenging. A multitude of genetic variants have been associated with immune-related diseases, including cancer, yet the interpretability of most variants remains low. Here, we investigate the quantitative components in the T cell receptor (TCR) repertoire, the frequency of clusters of TCR sequences predicted to have common antigen specificity, to interpret the genetic associations of diverse human diseases. We first developed a statistical model to predict the TCR components using variants in the TRB and HLA loci. Applying this model to over 300,000 individuals in the UK Biobank data, we identified 2309 associations between TCR abundances and various immune diseases. TCR clusters predicted to be pathogenic for autoimmune diseases were significantly enriched for predicted autoantigen-specificity. Moreover, four TCR clusters were associated with better outcomes in distinct cancers, where conventional GWAS cannot identify any significant locus. Collectively, our results highlight the integral role of adaptive immune responses in explaining the associations between genotype and phenotype.

Integrating single cell expression quantitative trait loci summary statistics to understand complex trait risk genes.

Transcriptome-wide association study (TWAS) is a popular approach to dissect the functional consequence of disease associated non-coding variants. Most existing TWAS use bulk tissues and may not have the resolution to reveal cell-type specific target genes. Single-cell expression quantitative trait loci (sc-eQTL) datasets are emerging. The largest bulk- and sc-eQTL datasets are most conveniently available as summary statistics, but have not been broadly utilized in TWAS. Here, we present a new method EXPRESSO (EXpression PREdiction with Summary Statistics Only), to analyze sc-eQTL summary statistics, which also integrates 3D genomic data and epigenomic annotation to prioritize causal variants. EXPRESSO substantially improves existing methods. We apply EXPRESSO to analyze multi-ancestry GWAS datasets for 14 autoimmune diseases. EXPRESSO uniquely identifies 958 novel gene x trait associations, which is 26% more than the second-best method. Among them, 492 are unique to cell type level analysis and missed by TWAS using whole blood. We also develop a cell type aware drug repurposing pipeline, which leverages EXPRESSO results to identify drug compounds that can reverse disease gene expressions in relevant cell types. Our results point to multiple drugs with therapeutic potentials, including metformin for type 1 diabetes, and vitamin K for ulcerative colitis.

Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets.

Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively). We showed that genetically determined reduction in renal expression may mimic the effects of rare loss-of-function variants on kidney mRNA/protein and lead to an increase in BP (e.g., ENPEP). We demonstrated a strong correlation (r = 0.81) in expression of protein-coding genes between cells harvested from urine and the kidney highlighting a diagnostic potential of urinary cell transcriptomics. We uncovered adenylyl cyclase activators as a repurposing opportunity for hypertension and illustrated examples of BP-elevating effects of anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our studies provide new biological insights into genetic regulation of BP with potential to drive clinical translation in hypertension.