VCP/p97 Extracts Sterically Trapped Ku70/80 Rings from DNA in Double-Strand Break Repair.

During DNA double-strand break (DSB) repair, the ring-shaped Ku70/80 complex becomes trapped on DNA and needs to be actively extracted, but it has remained unclear what provides the required energy. By means of reconstitution of DSB repair on beads, we demonstrate here that DNA-locked Ku rings are released by the AAA-ATPase p97. To achieve this, p97 requires ATP hydrolysis, cooperates with the Ufd1-Npl4 ubiquitin-adaptor complex, and specifically targets Ku80 that is modified by K48-linked ubiquitin chains. In U2OS cells, chemical inhibition of p97 or siRNA-mediated depletion of p97 or its adapters impairs Ku80 removal after non-homologous end joining of DSBs. Moreover, this inhibition attenuates early steps in homologous recombination, consistent with p97-driven Ku release also affecting repair pathway choice. Thus, our data answer a central question regarding regulation of Ku in DSB repair and illustrate the ability of p97 to segregate even tightly bound protein complexes for release from DNA.

Membrane-coated nanoparticles for direct recognition by T cells.

The direct modulation of T cell responses is an emerging therapeutic strategy with the potential to modulate undesired immune responses including, autoimmune disease, and allogeneic cells transplantation. We have previously demonstrated that poly(lactide-co-glycolide) particles were able to modulate T cell responses indirectly through antigen-presenting cells (APCs). In this report, we investigated the design of nanoparticles that can directly interact and modulate T cells by coating the membranes from APCs onto nanoparticles to form membrane-coated nanoparticles (MCNPs). Proteins within the membranes of the APCs, such as Major Histocompatibility Complex class II and co-stimulatory factors, were effectively transferred to the MCNP. Using alloreactive T cell models, MCNP derived from allogeneic dendritic cells were able to stimulate proliferation, which was not observed with membranes from syngeneic dendritic cells and influenced cytokine secretion. Furthermore, we investigated the engineering of the membranes either on the dendritic cells or postfabrication of MCNP. Engineered membranes could be to promote antigen-specific responses, to differentially activate T cells, or to directly induce apoptosis. Collectively, MCNPs represent a tunable platform that can directly interact with and modulate T cell responses.

Enhancing Biochar-Based Nonradical Persulfate Activation Using Data-Driven Techniques.

Converting biomass into biochar (BC) as a functional biocatalyst to accelerate persulfate activation for water remediation has attracted much attention. However, due to the complex structure of BC and the difficulty in identifying the intrinsic active sites, it is essential to understand the link between various properties of BC and the corresponding mechanisms promoting nonradicals. Machine learning (ML) recently demonstrated significant potential for material design and property enhancement to help tackle this problem. Herein, ML techniques were applied to guide the rational design of BC for the targeted acceleration of nonradical pathways. The results showed a high specific surface area, and O% values can significantly enhance nonradical contribution. Furthermore, the two features can be regulated by simultaneously tuning the temperatures and biomass precursors for efficient directed nonradical degradation. Finally, two nonradical-enhanced BCs with different active sites were prepared based on the ML results. This work serves as a proof of concept for applying ML in the synthesis of tailored BC for persulfate activation, thereby revealing the remarkable capability of ML for accelerating bio-based catalyst development.

Chemical Inhibition of RPA by HAMNO Alters Cell Cycle Dynamics by Impeding DNA Replication and G2-to-M Transition but Has Little Effect on the Radiation-Induced DNA Damage Response.

Replication protein A (RPA) is the major single-stranded DNA (ssDNA) binding protein that is essential for DNA replication and processing of DNA double-strand breaks (DSBs) by homology-directed repair pathways. Recently, small molecule inhibitors have been developed targeting the RPA70 subunit and preventing RPA interactions with ssDNA and various DNA repair proteins. The rationale of this development is the potential utility of such compounds as cancer therapeutics, owing to their ability to inhibit DNA replication that sustains tumor growth. Among these compounds, (1Z)-1-[(2-hydroxyanilino) methylidene] naphthalen-2-one (HAMNO) has been more extensively studied and its efficacy against tumor growth was shown to arise from the associated DNA replication stress. Here, we study the effects of HAMNO on cells exposed to ionizing radiation (IR), focusing on the effects on the DNA damage response and the processing of DSBs and explore its potential as a radiosensitizer. We show that HAMNO by itself slows down the progression of cells through the cell cycle by dramatically decreasing DNA synthesis. Notably, HAMNO also attenuates the progression of G2-phase cells into mitosis by a mechanism that remains to be elucidated. Furthermore, HAMNO increases the fraction of chromatin-bound RPA in S-phase but not in G2-phase cells and suppresses DSB repair by homologous recombination. Despite these marked effects on the cell cycle and the DNA damage response, radiosensitization could neither be detected in exponentially growing cultures, nor in cultures enriched in G2-phase cells. Our results complement existing data on RPA inhibitors, specifically HAMNO, and suggest that their antitumor activity by replication stress induction may not extend to radiosensitization. However, it may render cells more vulnerable to other forms of DNA damaging agents through synthetically lethal interactions, which requires further investigation.

Oxidative torrefaction of microalga Nannochloropsis Oceanica activated by potassium carbonate for solid biofuel production.

Oxidative torrefaction is a promising way for biomass upgrading and solid biofuel production. Alkali metals are considered to be efficient activators for enhancing biofuel upgrading during the thermal reaction process. Herein, the microalga Nannochloropsis Oceanica is selected as the feedstock for assessing potassium carbonate activated effect on solid biofuel production through oxidative torrefaction. The potential of potassium carbonate on microalgal biofuel properties upgrading is deeply explored. SEM observation and BET analysis show that torrefied microalgae can be transformed from a spherical structure with wrinkles to smaller particles with larger surface areas and higher total pore volumes, implying that potassium carbonate is a promising porogen. Moreover, potassium carbonate can significantly change the DTG curve at the temperatures of 250 °C and 300 °C from one peak to two peaks, inferring that the activated effect of potassium carbonate occurs on the torrefied microalgae. 13C NMR analysis reveals that the microalgal components significantly change as the torrefaction severity increases, with the decomposition of carbohydrate and protein components. When the potassium carbonate ratio increases from 0:1 to 1:1, the graphitization degree increase from 3.065 to 1.262, along with the increase in the HHV of solid biofuel from 25.024 MJ kg-1 to 31.890 MJ kg-1. In total, this study has comprehensively revealed the activated effect of potassium carbonate on improving the properties of microalgal solid biofuel.

A critical review on the treatment of dye-containing wastewater: Ecotoxicological and health concerns of textile dyes and possible remediation approaches for environmental safety.

The synthetic dyes used in the textile industry pollute a large amount of water. Textile dyes do not bind tightly to the fabric and are discharged as effluent into the aquatic environment. As a result, the continuous discharge of wastewater from a large number of textile industries without prior treatment has significant negative consequences on the environment and human health. Textile dyes contaminate aquatic habitats and have the potential to be toxic to aquatic organisms, which may enter the food chain. This review will discuss the effects of textile dyes on water bodies, aquatic flora, and human health. Textile dyes degrade the esthetic quality of bodies of water by increasing biochemical and chemical oxygen demand, impairing photosynthesis, inhibiting plant growth, entering the food chain, providing recalcitrance and bioaccumulation, and potentially promoting toxicity, mutagenicity, and carcinogenicity. Therefore, dye-containing wastewater should be effectively treated using eco-friendly technologies to avoid negative effects on the environment, human health, and natural water resources. This review compares the most recent technologies which are commonly used to remove dye from textile wastewater, with a focus on the advantages and drawbacks of these various approaches. This review is expected to spark great interest among the research community who wish to combat the widespread risk of toxic organic pollutants generated by the textile industries.

PTEN Loss Enhances Error-Prone DSB Processing and Tumor Cell Radiosensitivity by Suppressing RAD51 Expression and Homologous Recombination.

PTEN has been implicated in the repair of DNA double-strand breaks (DSBs), particularly through homologous recombination (HR). However, other data fail to demonstrate a direct role of PTEN in DSB repair. Therefore, here, we report experiments designed to further investigate the role of PTEN in DSB repair. We emphasize the consequences of PTEN loss in the engagement of the four DSB repair pathways-classical non-homologous end-joining (c-NHEJ), HR, alternative end-joining (alt-EJ) and single strand annealing (SSA)-and analyze the resulting dynamic changes in their utilization. We quantitate the effect of PTEN knockdown on cell radiosensitivity to killing, as well as checkpoint responses in normal and tumor cell lines. We find that disruption of PTEN sensitizes cells to ionizing radiation (IR). This radiosensitization is associated with a reduction in RAD51 expression that compromises HR and causes a marked increase in SSA engagement, an error-prone DSB repair pathway, while alt-EJ and c-NHEJ remain unchanged after PTEN knockdown. The G2-checkpoint is partially suppressed after PTEN knockdown, corroborating the associated HR suppression. Notably, PTEN deficiency radiosensitizes cells to PARP inhibitors, Olaparib and BMN673. The results show the crucial role of PTEN in DSB repair and show a molecular link between PTEN and HR through the regulation of RAD51 expression. The expected benefit from combination treatment with Olaparib or BMN673 and IR shows that PTEN status may also be useful for patient stratification in clinical treatment protocols combining IR with PARP inhibitors.

Exploring the potential of Cinnamomum zeylanicum oil against drug resistant Helicobacter pylori-producing cytotoxic genes.

Thirty-one of sixty dyspeptic patients tested positive for Helicobacter pylori colonization in this study, as determined by histopathology and 16S rRNA. The cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA) genes were found in 67.7 and 93.5% of H. pylori patients, respectively. The cagA gene was found to be associated with 100% of patients with duodenal erosion and ulceration identified via endoscopy examination. In addition, 86.7% of patients with cancerous and precancerous lesions, glandular atrophy, and intestinal metaplasia identified via histopathology examination. The vacA s1m1 mutation was associated with more severe forms of gastric erosion and ulceration, as well as the presence of precancerous and cancerous lesions. Eighteen (64.3%) of the twenty-eight isolates were classified as multi-drug resistant (MDR) or pan-drug resistant (PDR) H. pylori. Due to a resurgence of interest in alternative therapies derived from plants as a result of H. pylori resistance to the majority of commonly used antibiotics, the inhibitory activity of five essential oils extracted from some commonly used medicinal plants was evaluated in vitro against drug-resistant H. pylori clinical isolates. Cinnamomum zeylanicum essential oil demonstrated the highest anti-H. pylori activity when compared to the other essential oils tested. Cinnamaldehyde was the most abundant compound in C. zeylanicum (65.91%). The toxicological evaluation established the safety of C. zeylanicum oil for human use. As a result, C. zeylanicum essential oil may represent a novel antibacterial agent capable of combating drug-resistant H. pylori carrying cytotoxin genes.

Co-transesterification of waste cooking oil, algal oil and dimethyl carbonate over sustainable nanoparticle catalysts.

Key challenges for the application of biodiesel include their high acid value, high viscosity, and low ester content. It is essential to develop later-generation biodiesel from unexploited non-food resources for a more sustainable future. Reuse of biowaste is critically important to address these issues of food safety and sustainability. Thus, the co-transesterification of waste cooking oil (WCO), algal oil (AO) and dimethyl carbonate (DMC) for the synthesis of fatty acid methyl esters (FAMEs) was investigated over a series of nanoparticle catalysts containing calcium, magnesium, potassium or nickel under mild reaction conditions. Nanoparticle catalyst samples were prepared from biowaste sources of chicken manure (CM), water hyacinth (WH) and algal bloom (AB), and characterized using XRD, Raman and FESEM techniques for the heterogeneous production of biodiesel. The catalyst was initially prepared by calcination at 850 °C for 4 h in a major presence of CaxMgyCO3, KCl and K2CO3. The WCO and AO co-conversion of 98% and FAMEs co-selectivity of 95% were obtained over CM nanoparticle catalyst under the reaction conditions of 80 °C, 20 mins and DMC to oil molar ratio of 6:1 with 3% catalyst loading and 3% methanol addition. Under the optimum condition, the density, viscosity, and cetane number of the biodiesel were in the range of diesel standards. Nanoparticle catalysts have been proven as a promising sustainable material in the catalytic transesterification of WCO and AO with the major presence of calcium, magnesium and potassium. This study highlights a sustainable approach via biowaste utilization for the enhancement of biodiesel quality with high ester content, low acid value, high cetane number, and low viscosity.

Regulation of adipose tissue inflammation and systemic metabolism in murine obesity by polymer implants loaded with lentiviral vectors encoding human interleukin-4.

Dysfunctional adipose tissue plays a central role in the pathogenesis of the obesity-related metabolic disease, including type 2 diabetes. Targeting adipose tissue using biopolymer implants is a novel therapeutic approach for metabolic disease. We transplanted porous poly(lactide-co-glycolide) (PLG) implants coated with human interleukin-4 (hIL-4)-expressing lentivirus into epididymal white adipose tissue (eWAT) of mice fed a high-fat diet. Tissue and systemic inflammation and metabolism were studied with flow cytometry, immunohistochemistry, quantitative real-time polymerase chain reaction, adipose tissue histology, and in vivo glucose tolerance testing at 2 and 10 weeks of a high-fat diet. PLG implants carrying hIL-4-expressing lentivirus implanted into epididymal white adipose tissue of mice-regulated adipose tissue inflammation, including increased CD3+ CD4+ T-cell frequency, increased eWAT adipocyte hypertrophy, and decreased FASN and ATGL expression, along with reduced fasting blood glucose levels. These effects were observed in early obesity but were not maintained in established obesity. Local delivery of bioimplants loaded with cytokine-expressing lentivirus vectors to adipose tissue influences tissue inflammation and systemic metabolism in early obesity. Further study will be required to show more durable metabolic effects. These data demonstrate that polymer biomaterials implanted into adipose tissue have the potential to modulate local tissue and systemic inflammation and metabolism.

Chronic effects of repeated low-dose cisplatin treatment in mouse kidneys and renal tubular cells.

Cisplatin is a commonly used chemotherapeutic drug for cancer treatment, but its nephrotoxicity may lead to the deterioration of renal function. Previous work has been focused on cisplatin-induced acute kidney disease, whereas the mechanism of chronic kidney disease after cisplatin chemotherapy is largely unknown. In the present study, we have characterized the mouse model of chronic kidney defects induced by repeated low-dose cisplatin treatment. We have also established a relevant cell culture model. In the animal model, C57 mice were given weekly injection of 8 mg/kg cisplatin for 4 wk. This led to a sustained decline of kidney function. These mice showed loss of kidney mass, interstitial fibrosis, continued activation of inflammatory cytokines, and appearance of atubular glomeruli. In the cell model, the BUMPT mouse proximal tubular cell line was treated four times with 1-2 µM cisplatin, resulting in low levels of apoptosis and the expression of fibrosis proteins and profibrotic factors. These data suggest that repeated treatment with low-dose cisplatin causes long-term renal pathologies with characteristics of chronic kidney disease.

FGF21 is induced in cisplatin nephrotoxicity to protect against kidney tubular cell injury.

Cisplatin, a widely used cancer therapy drug, induces nephrotoxicity or acute kidney injury (AKI), but the underlying mechanism remains unclear, and renal protective approaches are not available. Fibroblast growth factor (FGF)21 is an endocrine factor that regulates glucose uptake, metabolism, and energy expenditure. However, recent work has also implicated FGF21 in cellular stress response under pathogenic conditions. The role and regulation of FGF21 in AKI are unclear. Here, we show that FGF21 was dramatically induced during cisplatin treatment of renal tubular cells in vitro and mouse kidneys in vivo. The inductive response was suppressed by pifithrin (a pharmacological inhibitor of P53), suggesting a role of P53 in FGF21 induction. In cultured renal tubular cells, knockdown of FGF21 aggravated cisplatin-induced apoptosis, whereas supplementation of recombinant FGF21 was protective. Consistently, recombinant FGF21 alleviated cisplatin-induced kidney dysfunction, tissue damage, and tubular apoptosis in mice. Mechanistically, FGF21 suppressed P53 induction and activation during cisplatin treatment. Together, these results indicate that FGF21 is induced during cisplatin nephrotoxicity to protect renal tubules, and recombinant FGF21 may have therapeutic potential.-Li, F., Liu, Z., Tang, C., Cai, J., Dong, Z. FGF21 is induced in cisplatin nephrotoxicity to protect against kidney tubular cell injury.

Study of CuSb bimetallic flow-through gas diffusion electrodes for efficient electrochemical CO2 reduction to CO.

Electrochemical CO2 reduction (eCO2R) to industrially important feedstock has received great attention, but it faces different challenges. Among them, the poor CO2 mass transport due to low intrinsic CO2 solubility significantly limits the rate of reduction reactions, leading to lower catalytic performance; thereby, commercially relevant current densities can't be achieved. Moreover, the poor activity and selectivity of high-cost monometallic catalysts, including Cu, Zn, Ag, and Au, undermine the efficiency of eCO2R. Flow-through gas diffusion electrodes (FTGDE), a newly developed class of GDEs, can potentially solve the issue of poor CO2 mass transport because they directly feed the CO2 to the catalyst layer. In addition, abundant surface area, porous structure, and improved triple-phase interface make them an excellent candidate for extremely high rate eCO2R. Antimony, a low-cost and abundant metalloid, can be effectively tuned with Cu to produce useful products such as CO, formate, and C2H4 through eCO2R. Herein, a series of porous binary CuSb FTGDEs with different Sb compositions are fabricated for the electrocatalytic reduction of CO2 to CO. The results show that the catalytic performance of CuSb FTGDEs improved with increasing Sb content up to a certain threshold, beyond which it started to decrease. The CuSb FTGDE with 5.4 g of antimony demonstrated higher current density (206.4 mA/cm2) and faradaic efficiency (72.82 %) at relatively lower overpotentials. Compared to gas diffusion configuration, the poor catalytic activity and selectivity achieved by CuSb FTGDE in non-gas diffusion configuration signifies the importance of improved local CO2 concentration and improved triple-phase interface formation in GDE configuration. The several hours stable operation of CuSb FTGDEs during eCO2R demonstrates its potential for efficient electrocatalytic conversion applications.

TRPC6 Knockout Alleviates Renal Fibrosis through PI3K/AKT/GSK3B Pathway.

OBJECTIVE: Renal fibrosis is the ultimate pathway of various forms of acute and chronic kidney damage. Notably, the knockout of transient receptor potential channel 6 (TRPC6) has shown promise in alleviating renal fibrosis. However, the regulatory impact of TRPC6 on renal fibrosis remains unclear. METHODS: In vivo, TRPC6 knockout (TRPC6-/-) mice and age-matched 129 SvEv (WT) mice underwent unilateral renal ischemia-reperfusion (uIR) injury surgery on the left renal pedicle or sham operation. Kidneys and serum were collected on days 7, 14, 21, and 28 after euthanasia. In vitro, primary tubular epithelial cells (PTECs) were isolated from TRPC6-/- and WT mice, followed by treatment with transforming growth factor ß1 (TGFß1) for 72 h. The anti-fibrotic effect of TRPC6-/- and the underlying mechanisms were assessed through hematoxylin-eosin staining, Masson staining, immunostaining, qRT-PCR, and Western blotting. RESULTS: Increased TRPC6 expression was observed in uIR mice and PTECs treated with TGFß1. TRPC6-/- alleviated renal fibrosis by reducing the expression of fibrotic markers (Col-1, α-SMA, and vimentin), as well as decreasing the apoptosis and inflammation of PTECs during fibrotic progression both in vivo and in vitro. Additionally, we found that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3ß) signaling pathway, a pivotal player in renal fibrosis, was down-regulated following TRPC6 deletion. CONCLUSION: These results suggest that the ablation of TRPC6 may mitigate renal fibrosis by inhibiting the apoptosis and inflammation of PTECs through down-regulation of the PI3K/AKT/GSK3ß pathway. Targeting TRPC6 could be a novel therapeutic strategy for preventing chronic kidney disease.

Chemokine CXCL14 is associated with prognosis in patients with colorectal carcinoma after curative resection.

BACKGROUND: The chemokine CXCL14 has been reported to play an important role in the progression of many malignancies such as breast cancer and papillary thyroid carcinoma, but the role of CXCL14 in colorectal carcinoma (CRC) remains to be established. The purpose of this study was to investigate the expression pattern and significance of CXCL14 in CRC progression. METHOD: 265 colorectal carcinoma specimens and 129 matched adjacent normal colorectal mucosa specimens were collected. Expression of CXCL14 in clinical samples was examined by immunostaining. The effect of CXCL14 on colorectal carcinoma cell proliferation was measured by MTT assay, BrdU incorporation assay and colony formation assay. The impact of CXCL14 on migration and invasion of colorectal carcinoma cells was determined by transwell assay and Matrigel invasion assay, respectively. RESULTS: CXCL14 expression was significantly up-regulated in tumor tissues compared with adjacent nontumorous mucosa tissues (P < 0.001). Tumoral CXCL14 expression levels were significantly correlated with TNM (Tumor-node-metastasis) stage, histodifferentiation, and tumor size. In multivariate Cox regression analysis, high CXCL14 expression in tumor specimens (n = 91) from stage I/II patients was associated with increased risk for disease recurrence (risk ratio, 2.92; 95% CI, 1.15-7.40; P = 0.024). Elevated CXCL14 expression in tumor specimens (n = 135) from stage III/IV patients correlated with worse overall survival (risk ratio, 3.087; 95% CI, 1.866-5.107; P < 0.001). Functional studies demonstrated that enforced expression of CXCL14 in SW620 colorectal carcinoma cells resulted in more aggressive phenotypes. In contrast, knockdown of CXCL14 expression could mitigate the proliferative, migratory and invasive potential of HCT116 colorectal carcinoma cells. CONCLUSION: Taken together, CXCL14 might be a potential novel prognostic factor to predict the disease recurrence and overall survival and could be a potential target of postoperative adjuvant therapy in CRC patients.

Three-dimensional hierarchical architectures constructed by graphene/MoS2 nanoflake arrays and their rapid charging/discharging properties as lithium-ion battery anodes.

Charged up: Three-dimensional architectures constructed from graphene/MoS2 nanoflake arrays have been successfully fabricated by a one-step hydrothermal method. MoS2 nanoflakes with thicknesses less than 13 nm grow vertically on both sides of graphene sheets (see figure), which allows the architectures to be more stable during charging and discharging. Even at a high current density of 8000 mA g(-1), their discharge capacity is still up to 516 mA h g(-1).

Ammonium nitrogen removal in batch cultures treating digested piggery wastewater with microalgae Oedogonium sp.

Due to the nutrient characteristics of the high concentration of available ammonium in digested piggery wastewater (DPW), microalgae can be used to treat DPW before its final discharge. Four green microalgae (Hydrodictyaceae reticulatum Lag, Scenedesmus obliquus, Oedogonium sp. and Chlorella pyrenoidosa) and three blue-green algae (Anabaena flos-aquae, Oscillatoria amoena Gom and Spirulina platensis) were used to remove the nutrients (N, P, C), especially ammonium nitrogen (NH4(+)-N), from diluted DPW with 300 mg/L algae density in batch tests. The microalgae with the best NH4(+)-N nutrient removal was then selected for further optimization of the variables to improve NH4(+)-N removal efficiency using a central composite design (CCD) experiment. Taking into account the nutrient removal efficiency, Oedogonium sp. showed the best performance (reduction of 95.9% NH4(+)-N, 92.9% total phosphorus (TP) and 62.5% chemical oxygen demand (COD)) based on the results of the batch tests. The CCD results suggested that the optimal values of variables were initial Oedogonium sp. density of 399.2 mg/L and DPW diluted by 16.3, while the predicted value of NH4(+)-N removal efficiency obtained was 97.0%.

Trends in using of antihypertensive medication among US CKD adults, NHANES 2001-2018.

Objective: Blood pressure (BP) control rates among adult patients taking antihypertensive medications in the United States have not improved over the last decade. Many CKD adults require more than one class of antihypertensive agent to reach the BP target recommended by the guidelines. However, no study has quantified the proportion of adult CKD patients taking antihypertensive medication who are on monotherapy or combination therapy. Methods: National Health and Nutrition Examination Survey data during 2001-2018 was used, including adults with CKD taking antihypertensive medication (age ≥ 20 years, n = 4,453). BP control rates were investigated under the BP targets recommended by the 2021 KDIGO, the 2012 KDIGO, and the 2017 ACC/AHA guidelines. Results: The percentages of uncontrolled BP among US adults with CKD taking antihypertensive medication were 81.4% in 2001-2006 and 78.2% in 2013-2018. The proportion of monotherapy of antihypertensive regimen were 38.6, 33.3, and 34.6% from 2001 to 2006, 2007-2012, and 2013-2018, with no obvious difference. Similarly, there was no significant change in percentages of dual-therapy, triple-therapy, and quadruple-therapy. Although proportion of CKD adults not treated with ACEi/ARB decreased from 43.5% in 2001-2006 to 32.7% in 2013-2018, treatment of ACEi/ARB among patients with ACR > 300 mg/g had no significant change. Conclusion: The BP control rates among US adult CKD patients taking antihypertensive medications have not improved from 2001 to 2018. Mono-therapy accounted for about one third of adult CKD patients taking antihypertensive medication and not changed. Increasing antihypertensive medication combination therapy may help improve BP control in CKD adults in the United States.

Direct Z-scheme heterojunction Bi/Bi2S3/α-MoO3 photoelectrocatalytic degradation of tetracycline under visible light.

A hot research topic in visible-light-driven photoelectrocatalytic (PEC) oxidation technology is the development of superior photoanode materials. The design of the photoanode system with a direct Z-scheme charge transfer mechanism is crucial to achieving effective charge separation for sustainable photoelectrocatalysis. Here, a novel Bi/Bi2S3/α-MoO3 heterostructure was successfully assembled by a simple and feasible strategy. The direct Z-scheme heterogeneous formed between Bi2S3 and α-MoO3 has the advantages of low resistance, high optical response current and the surface plasmon resonance (SPR) effect of Bi nanoparticles (Bi NPs). Thus, the efficiency of photogenerated carrier separation and transfer is further enhanced, and the catalytic activity is significantly improved. It is impressive that the unique photoanode has achieved a maximum removal efficiency of 85.8% of tetracycline (TC) pollutants under visible light irradiation within 60 min and has excellent stability, which is expected to degrade antibiotics efficiently and environmentally in harsh environments. These characteristics give Bi/Bi2S3/α-MoO3 promising candidates for practical applications in antibiotic degradation.

Low CDK Activity and Enhanced Degradation by APC/CCDH1 Abolishes CtIP Activity and Alt-EJ in Quiescent Cells.

Alt-EJ is an error-prone DNA double-strand break (DSBs) repair pathway coming to the fore when first-line repair pathways, c-NHEJ and HR, are defective or fail. It is thought to benefit from DNA end-resection-a process whereby 3' single-stranded DNA-tails are generated-initiated by the CtIP/MRE11-RAD50-NBS1 (MRN) complex and extended by EXO1 or the BLM/DNA2 complex. The connection between alt-EJ and resection remains incompletely characterized. Alt-EJ depends on the cell cycle phase, is at maximum in G2-phase, substantially reduced in G1-phase and almost undetectable in quiescent, G0-phase cells. The mechanism underpinning this regulation remains uncharacterized. Here, we compare alt-EJ in G1- and G0-phase cells exposed to ionizing radiation (IR) and identify CtIP-dependent resection as the key regulator. Low levels of CtIP in G1-phase cells allow modest resection and alt-EJ, as compared to G2-phase cells. Strikingly, CtIP is undetectable in G0-phase cells owing to APC/C-mediated degradation. The suppression of CtIP degradation with bortezomib or CDH1-depletion rescues CtIP and alt-EJ in G0-phase cells. CtIP activation in G0-phase cells also requires CDK-dependent phosphorylation by any available CDK but is restricted to CDK4/6 at the early stages of the normal cell cycle. We suggest that suppression of mutagenic alt-EJ in G0-phase is a mechanism by which cells of higher eukaryotes maintain genomic stability in a large fraction of non-cycling cells in their organisms.