Adsorption of Cu (II) and Zn (II) in aqueous solution by modified bamboo charcoal.

Due to the development of industries such as mining, smelting, industrial electroplating, tanning, and mechanical manufacturing, heavy metals were discharged into water bodies seriously affecting water quality. Bamboo charcoal, as an environmentally friendly new adsorbent material, in this paper, the virgin bamboo charcoal (denoted as WBC) was modified with different concentrations of KMnO4 and NaOH to obtain KMnO4-modified bamboo charcoal (KBC) and NaOH-modified bamboo charcoal (NBC) which was used to disposed of water bodies containing Cu2+ and Zn2+. The main conclusions were as following: The adsorption of Cu2+ by WBC, KBC and NBC was significantly affected by pH value, and the optimum pH was 5.0. Differently, the acidity and alkalinity of the solution doesn't effect the adsorption of Zn2+ seriousely. Meanwhile, surface diffusion and pore diffusion jointly determine the adsorption rate of Cu2+ and Zn2+. The test result of EDS showed that Mn-O groups formed on the surface of K6 (WBC treated by 0.06 mol/L KMnO4) can promote the adsorption of Cu2+ and Zn2+ at a great degree. The O content on N6(WBC treated by 6 mol/L NaOH) surface increased by 30.95% compared with WBC. It is speculated that the increase of carbonyl group on the surface of NBC is one of the reasons for the improvement of Cu2+ and Zn2+ adsorption capacity. Finally, the residual concentrations of Cu2+ and Zn2+ in wastewater are much lower than 0.5 mg/L and 1.0 mg/L, respectively. Thus it can be seen, KBC and NBC could be a promising adsorbent for heavy metals.

The Combined Effect of Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors on Thyroid Function.

Background: Recent successes with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the treatment of solid malignancies have paved the way for a new era of combined therapy. A common side effect seen with each of these classes of treatment is thyroid dysfunction, with rates estimated at 30-40% for TKI and 10-20% for ICI. However, little is known about the effect of combined ICI+TKI therapy on thyroid function. Therefore, this study evaluated the incidence, clinical features, and risk factors for developing thyroid abnormalities during ICI+TKI therapy and the relationship to cancer outcomes. Methods: We conducted a retrospective cohort study of patients treated with combination ICI+TKI cancer therapy at City of Hope Comprehensive Cancer Center from 2017 to 2023 who had pretreatment normal thyrotropin (TSH) levels. Primary analyses assessed the frequency, timing, and severity of thyroid function test abnormalities during ICI+TKI cancer therapy, and the requirement for thyroid hormone replacement. Secondary analyses evaluated risk factors for the development of thyroid dysfunction, including sex and drug regimen, and the association with cancer progression-free survival or overall survival. Univariable and multivariable models were used. Results: There were 106 patients who received ICI+TKI therapy with a median age of 63.5 years and a median follow-up of 12.8 months (interquartile range [IQR] 5.9-20.9). Notably, 63.2% (67/106) developed thyroid function abnormalities during ICI+TKI therapy, including 11 (10.4%) with hyperthyroidism, 42 (39.6%) with subclinical hypothyroidism (SCHypo), and 14 (13.2%) with overt hypothyroidism. The onset of thyroid dysfunction occurred at a median of 7 weeks (IQR 3.1-9.0) after start of ICI+TKI treatment for hyperthyroidism, 8.0 weeks (IQR 3.0-19.0) for SCHypo, and 8.1 weeks (IQR 5.9-9.1) for overt or worsening hypothyroidism. Hyperthyroidism resolved to hypothyroidism or normal TSH without intervention in all subjects, suggesting thyroiditis, and hypothyroidism was readily treated with thyroid hormone replacement. Conclusions: Thyroid dysfunction is a frequent adverse event in individuals treated with combination ICI+TKI therapy, with our data suggesting a rapid onset and higher incidence than previously seen with ICI or TKI therapy alone. Therefore, close monitoring of thyroid function during initial therapy and multidisciplinary care with endocrinology are recommended to facilitate early detection and initiation of thyroid hormone replacement in these patients.

Sodium Selenite Ameliorates Silver Nanoparticles Induced Vascular Endothelial Cytotoxic Injury by Antioxidative Properties and Suppressing Inflammation Through Activating the Nrf2 Signaling Pathway.

Silver nanoparticles (AgNP) are the dominant nanomaterials in commercial products and the medical field, but the widespread occurrence of AgNP has become a global threat to human health. Growing studies indicate that AgNP exposure can induce vascular endothelial toxicity by excessive oxidative stress and inflammation, which is closely related to cardiovascular disease (CVD), but the potential intrinsic mechanism remains poorly elucidated. Thus, it has been crucial to control the toxicological effects of AgNP in order to improve their safety and increase the outcome of their applications.Multiple researches have demonstrated that sodium selenite (Se) possesses the capability to counteract the toxicity of AgNP, but the functional role of Se in AgNP-induced CVD is largely unexplored. The aim of this study was to explore the potential protective effect of Se on AgNP-induced vascular endothelial lesion and elucidate the underlying mechanisms. An in vivo model of toxicity in animals was established by the instillation of 200 µL of AgNP into the trachea of rats both with (0.2 mg/kg/day) and without Se treated. In vitro experiments, human umbilical vein endothelial cells (HUVECs) were incubated with AgNP (0.3 µg/mL ) and Se for a duration of 24 h. Utilizing transmission electron microscopy, we observed that the internalization of AgNP-induced endothelial cells was desquamated from the internal elastic lamina, the endoplasmic reticulum was dilated, and the medullary vesicle formed. Se treatment reduced the levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), inhibited the release of pro-inflammatory cytokines (specifically tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6), improved endothelial cell permeability, integrity, and dysfunction, and prevented damage to the aortic endothelium caused by AgNP. Importantly, we found that Se showed the capacity against AgNP with biological functions in guiding the intracellular reactive oxygen species (ROS) scavenging and meanwhile exhibiting anti-inflammation effects. Se supplementation decreased the intracellular ROS release and suppressed NOD-like receptor protein 3 (NLRP3) and nuclear factor kappa-B (NF-κB) mediated inflammation within AgNP-intoxicated rats and HUVECs. The anti-oxidant stress and anti-inflammatory effects of Se were at least partly dependent on nuclear factor erythroid 2-related factor 2 (Nrf2). Overall, our results indicated that the protectiveness of Se against AgNP-induced vascular endothelial toxicity injury was at least attributed to the inhibition of oxidative ROS and pro-inflammatory NF-κB/NLRP3 inflammasome by activating the Nrf2 and antioxidant enzyme (HO-1) signal pathway.

Contributions of global and local processing on medical image perception.

Purpose: The influential holistic processing hypothesis attributes expertise in medical image perception to cognitive processing of global gist information. However, it has remained unclear whether or how experts use rapid global impression of images for their subsequent diagnostic decisions based on the focal sign of cancer. We hypothesized that continuous-global and discrete-local processes jointly attribute to radiological experts' detection of mammogram, with different weights and temporal dynamics. Approach: We examined experienced versus inexperienced observers' performance at first (500 ms) versus second (2500 ms) mammogram image presentation in an abnormality detection task. We applied a dual-trace signal detection (DTSD) model of receiver operating characteristic (ROC) to assess the time-varying contributions of global and focal cancer signals on mammogram reading and medical expertise. Results: The hierarchical Bayesian DTSD modeling of empirical ROCs revealed that mammogram expertise (experienced versus inexperienced observers) manifests largely in a continuous-global component for the detection of the gist of abnormality at the early phase of mammogram reading. For the second presentation of the same mammogram images, the experienced participants showed increased task performance that was largely driven by better processing of discrete-local information, whereas the global processing of abnormality remained saturated from the first exposure. Modeling of the mouse trajectory of the confidence rating responses further revealed the temporal dynamics of global and focal processing. Conclusions: These results suggest a joint contribution of continuous-global and discrete-local processes on medical expertise, and these processes could be analytically dissociated.

Aspirin ameliorates atherosclerotic immuno-inflammation through regulating the Treg/Th17 axis and CD39-CD73 adenosine signaling via remodeling the gut microbiota in ApoE-/- mice.

The gut microbiome has been implicated in the development of cardiovascular disease (CVD) and atherosclerosis (AS), a chronic inflammatory condition. Aspirin may improve the immuno-inflammatory status in AS by regulating microbiota dysbiosis. However, the potential role of aspirin in modulating gut microbiota and microbial-derived metabolites remains less explored. In this study, we investigated the effect of aspirin treatment on AS progression by modulating gut microbiota and microbial-derived metabolites in apolipoprotein E-deficient (ApoE-/-) mice. We analyzed the fecal bacterial microbiome and targeted metabolites, including short-chain fatty acids (SCFAs) and bile acids (BAs). The immuno-inflammatory status of AS was evaluated by analyzing regulatory T cells (Tregs), Th17 cells, and the CD39-CD73 adenosine signaling pathway involved in purinergic signaling. Our results indicated that aspirin altered gut microbiota, leading to an increase in the phylum Bacteroidetes and a decrease in the Firmicutes to Bacteriodetes (F/B) ratio. Aspirin treatment also increased levels of targeted SCFA metabolites, such as propionic acid, valeric acid, isovaleric acid, and isobutyric acid. Furthermore, aspirin impacted BAs by reducing the level of harmful deoxycholic acid (DCA) and increasing the levels of beneficial isoalloLCA and isoLCA. These changes were accompanied by a rebalancing of the ratio of Tregs to Th17 cells and an increase in the expression of ectonucleotidases CD39 and CD73, thereby ameliorating inflammation. These findings suggest that aspirin has an athero-protective effect with an improved immuno-inflammatory profile, partially attributed to its manipulation of the gut microbiota.

Butyrate suppresses atherosclerotic inflammation by regulating macrophages and polarization via GPR43/HDAC-miRNAs axis in ApoE-/- mice.

Chronic low-grade inflammation is regarded to an important signature of atherosclerosis (AS). Macrophage (Mψ) and related polarization have been demonstrated to play a crucial role in the occurrence and development of AS inflammation. Butyrate, a bioactive molecule produced by the intestinal flora, has been increasingly demonstrated to exhibit a vital role for regulating the inflammation in chronic metabolic diseases. However, the effectiveness and multiple anti-inflammation mechanisms of butyrate on AS still need to be further understood. ApoE-/- mice fed with high-fat diet as AS model were administered with sodium butyrate (NaB) for 14 weeks of treatment. Our results showed that the atherosclerotic lesion in the AS group was dramatically reduced after NaB intervention. Moreover, deteriorated routine parameters of AS including body weights (BWs), low-density lipoprotein (LDL-C), triglyceride (TG), total cholesterol (TC) were significantly reversed by NaB administration. Abnormal elevated plasma and aorta pro-inflammatory indicators including interleukin (IL)-1ß, IL-6, IL-17A, tumor necrosis factor (TNF)-α and lipopolysaccharide (LPS), as well as reduced anti-inflammatory IL-10 in plasma were respectively rectified after NaB administration. Consistently, accumulated Mψ and associated imbalance of polarization in the arota were attenuated with NaB treatment. Importantly, we demonstrated that the suppression of Mψ and associated polarization of NaB was dependent on binding G-protein coupled receptor (GPR) and inhibiting histone deacetylase HDAC3. Moreover, we found that intestinal butyrate-producing bacteria, anti-inflammatory bacteria and intestinal tight junction protein zonula occludens-1 (ZO)-1 may contribute to this effectiveness. Intriguingly, according to transcriptome sequencing of atherosclerotic aorta, 29 elevated and 24 reduced miRNAs were found after NaB treatment, especially miR-7a-5p, suggesting that non-coding RNA may possess a potential role in the protection of NaB against AS. Correlation analysis showed that there were close complicated interactions among gut microbiota, inflammation and differential miRNAs. Collectively, this study revealed that dietary NaB may ameliorate atherosclerotic inflammation by regulating Mψ polarization via GPR43/HDAC-miRNAs axis in ApoE-/- mice.

A "Pre-Division Metal Clusters" Strategy to Mediate Efficient Dual-Active Sites ORR Catalyst for Ultralong Rechargeable Zn-Air Battery.

To conquer the bottleneck of sluggish kinetics in cathodic oxygen reduction reaction (ORR) of metal-air batteries, catalysts with dual-active centers have stood out. Here, a "pre-division metal clusters" strategy is firstly conceived to fabricate a N,S-dual doped honeycomb-like carbon matrix inlaid with CoN4 sites and wrapped Co2 P nanoclusters as dual-active centers (Co2 P/CoN4 @NSC-500). A crystalline {CoII 2 } coordination cluster divided by periphery second organic layers is well-designed to realize delocalized dispersion before calcination. The optimal Co2 P/CoN4 @NSC-500 executes excellent 4e- ORR activity surpassing the benchmark Pt/C. Theoretical calculation results reveal that the CoN4 sites and Co2 P nanoclusters can synergistically quicken the formation of *OOH on Co sites. The rechargeable Zn-air battery (ZAB) assembled by Co2 P/CoN4 @NSC-500 delivers ultralong cycling stability over 1742 hours (3484 cycles) under 5 mA cm-2 and can light up a 2.4 V LED bulb for ≈264 hours, evidencing the promising practical application potentials in portable devices.

Sprayable NAHAO® hydrogel alleviates pain and accelerates rat oral mucositis wound healing.

OBJECTIVE: To investigate the promote healing and analgesic effects of NAHAO® Brand Nazhen oral antibacterial care solution (NAHAO® spray) on the 5-fluorouracil-induced oral mucositis in rats. MATERIAL AND METHOD: Sixty male SD rats were randomly divided into normal group, model group, recombinant human epidermal growth factor (rhEGF) group, NAHAO® spray group, and 1/3 concentration of NAHAO® spray group. 5-FU was injected intraperitoneally on the first and third days of the experimental model, and OM was induced using mechanical trauma on the third and fifth days. Wound healing quality was assessed by the appearance of mucosa and histological images on day6 and day10. Pain is measured by facial grooming behavior stimulated by capsaicin, the alternation of body weight and food intake was also recorded to reflect the OM pain. To examine the involvement of the cyclooxygenase pathway in the mechanism underlying oral mucositis, we detected the expression of cyclooxygenase2(COX-2) and matrix metalloproteinase 9(MMP9) via immunohistochemical staining and determined the PGE2 concentrations in rats' serum during healing of oral mucositis. RESULTS: NAHAO® spray attenuated pathological damage and reduced pain sensitivity effectively. COX-2 expression levels were inhibited in the NAHAO® spray-treated group. The concentration of PGE2 and the expression of MMP9 were inhibited in NAHAO®-treated rats. Compared with normal rats, the elevated rubbing time following capsaicin stimulation in the model was completely inhibited after being treated with NAHAO® spray. CONCLUSION: NAHAO® spray alleviated OM-induced pain and promoted wound healing partly by inhibiting the cyclooxygenase-related pathway.

Computed Tomography Angiography and Conventional Angiography for the Diagnosis and Treatment of Non-variceal Gastrointestinal Bleeding at a Tertiary Cancer Center.

INTRODUCTION: To evaluate the diagnostic value of computed tomography angiography (CTA) and conventional angiography (CA) and the therapeutic value of transarterial embolization for acute gastrointestinal bleeding in patients with malignancy. METHODS: A retrospective review of 100 patients who underwent CTA and/or CA for gastrointestinal bleeding at a comprehensive cancer center between the years 2011-2021 was performed. Clinical and patient outcome data were collected and analyzed using Kruskal-Wallis tests for continuous variables and chi-square tests or Fisher's exact tests (whichever is appropriate) for categorical variables in univariate analysis. All tests were two-sided at a significance level of 0.05. Analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC). RESULTS: Fifty-two percent of our patients underwent CTA alone, 29% underwent CA alone, and 19% underwent both procedures. Overall, CTA was positive in 11.3% (8/71) of patients and CA was positive in 22.9% (11/38) of patients. Of patients who underwent both studies, 52.6% (10/19) were positive for both. ICU admission was associated with CTA and/or CA positivity (p=0.015). Of 48 patients with data for embolization, 50% of patients underwent transarterial embolization for bleeding, 11 patients had identifiable bleeding on CA, and 13 patients underwent prophylactic embolization at the site of suspected bleeding. Rebleeding following embolization was found in 33.3% (8/24) of patients, including six patients who underwent prophylactic embolization and two patients who were treated for visualized bleeding. CONCLUSION: CTA and CA are two critical studies for patients with GI bleeding and a history of malignancy. Neither alone can effectively exclude an identifiable source of bleeding. In patients with a history of malignancy, transarterial embolization may be an effective treatment of both angiographically visible and occult sources of GI bleeding.

The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density.

BACKGROUND: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk. METHODS: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche. RESULTS: In pooled analyses, later age at menarche was associated with higher per cent density (ß√PD = 0.023 SE = 0.008, P = 0.003) and larger dense area (ß√DA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (ß√DA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (ß√PD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups. CONCLUSIONS: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density.

Interpenetrated N-rich MOF derived vesicular N-doped carbon for high performance lithium ion battery.

High-performance lithium ion batteries (LIBs) juggling high reversible capacity, excellent rate capability and ultralong cycle stability are urgently needed for all electronic devices. Here we report employing a vesicle-like porous N-doped carbon material (abbr. N/C-900) as a highly active anode for LIBs to balance high capacity, high rate and long life. The N/C-900 material was fabricated by pyrolysis of a designed crystal MOF LCU-104, which exhibits a graceful two-fold interpenetrating structural feature of N-rich nanocages {Zn6(dttz)4} linked through an N-donor ligand bpp (H3dttz = 4,5-di(1H-tetrazol-5-yl)-2H-1,2,3-triazole, bpp = 1,3-bis(4-pyridyl)propane). The features of LCU-104 combine high N content (35.1%), interpenetration, and explosive characteristics, which endow the derived N/C material with optimized N-doping for tuning its chemical and electronic structure, a suitably thicker wall to enhance its stability, and a vesicle-like structure to improve its porosity. As an anode material for LIBs, N/C-900 delivers a highly reversible capacity of ca. 734 mA h g-1 at a large current density of 1 A g-1 until the 2000th cycle, revealing its ultralong cycle stability and excellent rate capability. The unique structure and preferential interaction between abundant pyridinic N active sites and Li atoms are responsible for the improved excellent lithium storage capacity and durability performances of the anode according to analysis of the results of computational modeling.

Dietary α-Linolenic Acid-Rich Flaxseed Oil Ameliorates High-Fat Diet-Induced Atherosclerosis via Gut Microbiota-Inflammation-Artery Axis in ApoE -/- Mice.

Atherosclerosis (AS) is closely associated with abnormally chronic low-grade inflammation and gut dysbiosis. Flaxseed oil (FO) rich in omega-3 polyunsaturated fatty acids (PUFAs), which are mainly composed of alpha-linolenic acid (ALA, 18:3 omega-3), has been demonstrated to exhibit pleiotropic benefits in chronic metabolic diseases. However, the impact of dietary ALA-rich FO on AS and its associated underlying mechanisms remain poorly understood. Thus, the present study was designed as two phases to investigate the effects in atherosclerotic Apolipoprotein E (ApoE)-/- mice. In the initial portion, the ApoE -/- mice were randomly allocated to three groups: control group (CON), model group (MOD), and FO-fed model group (MOD/FO) and were treated for 12 weeks. The second phase used antibiotic (AB)-treated ApoE -/- mice were divided into two groups: AB-treated model group (AB/MOD) and FO-fed AB-treated model group (AB/FO). In the results, the dietary ALA-rich FO administration ameliorated atherosclerotic lesion, as well as the parameters of AS (body weights (BWs) and the total bile acids (TBA). Chronic systemic/vascular inflammatory cytokines and in situ macrophages (Mψs) were reduced with FO intervention. In addition, the FO improved the gut integrity and permeability by decreasing the plasma lipopolysaccharide (LPS). Moreover, gut dysbiosis and metabolites [short-chain fatty acids (SCFAs) and bile acids (BAs)] in AS were modulated after FO treatment. Intriguingly, during an AB-treated condition, a significantly weakened amelioration of FO-treated on AS proposed that the intestinal microbiota contributed to the FO effects. A correlation analysis showed close relationships among gut bacteria, metabolites, and inflammation. Collectively, these results suggested that the dietary ALA-rich FO ameliorated the AS in ApoE -/- mice via the gut microbiota-inflammation-artery axis.

Hierarchical Fe-Mn binary metal oxide core-shell nano-polyhedron as a bifunctional electrocatalyst for efficient water splitting.

Electrochemical water splitting is convinced as one of the most promising solutions to combat the energy crisis. The exploitation of efficient hydrogen and oxygen evolution reaction (HER/OER) bifunctional electrocatalysts is undoubtedly a vital spark yet challenging for imperative green sustainable energy. Herein, through introducing a simple pH regulated redox reaction into a tractable hydrothermal procedure, a hierarchical Fe3O4@MnOx binary metal oxide core-shell nano-polyhedron was designed by evolving MnOx wrapped Fe3O4. The MnOx effectively prevents the agglomeration and surface oxidation of Fe3O4 nano-particles and increases the electrochemically active sites. Benefiting from the generous active sites and synergistic effects of Fe3O4 and MnOx, the Fe3O4@MnOx-NF nanocomposite implements efficient HER/OER bifunctional electrocatalytic performance and overall water splitting. As a result, hierarchical Fe3O4@MnOx only requires a low HER/OER overpotential of 242/188 mV to deliver 10 mA cm-2, a small Tafel slope of 116.4/77.6 mV dec-1, combining a long-term cyclability of 5 h. Impressively, by applying Fe3O4@MnOx as an independent cathode and anode, the overall water splitting cell supplies a competitive voltage of 1.64 V to achieve 10 mA cm-2 and super long cyclability of 80 h. These results reveal that this material is a promising candidate for practical water electrolysis application.

Unraveling the Mechanism of Aerobic Alcohol Oxidation by a Cu/pytl-ß-Cyclodextrin/TEMPO Catalytic System under Air in Neat Water.

The mechanism for the oxidation of p-tolylmethanol to p-tolualdehyde catalyzed by a Cu/pytl-ß-cyclodextrin/TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidinyl-1-oxy) catalytic system under air in neat water is fully investigated by density functional theory (DFT). Four possible pathways (paths A → D) are presented. The calculated TOF = 0.67 h-1 for path A is consistent with the experimental TOF = 1.9 h-1 but much lower than that for path D (TOF = 1.1 × 105 h-1). The results demonstrate that path A is the dominant pathway under the optimal experimental conditions, even though path D is more kinetically favorable. This is because the concentration of precatalyst 11 [(pytl-ß-CD)CuII(OH)] in path D is too low to start path D, so p-tolylmethanol oxidation can only proceed via path A. This finding implies that the relative concentration of precatalysts in a one-pot synthesis experiment plays a vital role in the aerobic alcohol oxidation reaction. Based on this finding, we speculate that the direct use of the presynthesized precatalyst 11 or addition of an appropriate amount of NaOH to the reaction solution, but with the total amount of the base added unchanged, is a good way to improve its catalytic activity. Meanwhile, the solvent water was not found to directly participate in the catalytic active sites for the oxidation of alcohols but rather inhibited it by forming the hydrogen-bonded network.

Risk of Late-Onset Breast Cancer in Genetically Predisposed Women.

PURPOSE: The prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes in women in the general population over age 65 years is not well-defined. However, testing guidelines suggest that women diagnosed with breast cancer over age 65 years might have < 2.5% likelihood of a PV in a high-penetrance gene. This study aimed to establish the frequency of PVs and remaining risks of breast cancer for each gene in women over age 65 years. METHODS: A total of 26,707 women over age 65 years from population-based studies (51.5% with breast cancer and 48.5% unaffected) were tested for PVs in germline predisposition gene. Frequencies of PVs and associations between PVs in each gene and breast cancer were assessed, and remaining lifetime breast cancer risks were estimated for non-Hispanic White women with PVs. RESULTS: The frequency of PVs in predisposition genes was 3.18% for women with breast cancer and 1.48% for unaffected women over age 65 years. PVs in BRCA1, BRCA2, and PALB2 were found in 3.42% of women diagnosed with estrogen receptor (ER)-negative, 1.0% with ER-positive, and 3.01% with triple-negative breast cancer. Frequencies of PVs were lower among women with no first-degree relatives with breast cancer. PVs in CHEK2, PALB2, BRCA2, and BRCA1 were associated with increased risks (odds ratio = 2.9-4.0) of breast cancer. Remaining lifetime risks of breast cancer were ≥ 15% for those with PVs in BRCA1, BRCA2, and PALB2. CONCLUSION: This study suggests that all women diagnosed with triple-negative breast cancer or ER-negative breast cancer should receive genetic testing and that women over age 65 years with BRCA1 and BRCA2 PVs and perhaps with PALB2 and CHEK2 PVs should be considered for magnetic resonance imaging screening.

Risk of Breast Cancer Among Carriers of Pathogenic Variants in Breast Cancer Predisposition Genes Varies by Polygenic Risk Score.

PURPOSE: This study assessed the joint association of pathogenic variants (PVs) in breast cancer (BC) predisposition genes and polygenic risk scores (PRS) with BC in the general population. METHODS: A total of 26,798 non-Hispanic white BC cases and 26,127 controls from predominately population-based studies in the Cancer Risk Estimates Related to Susceptibility consortium were evaluated for PVs in BRCA1, BRCA2, ATM, CHEK2, PALB2, BARD1, BRIP1, CDH1, and NF1. PRS based on 105 common variants were created using effect estimates from BC genome-wide association studies; the performance of an overall BC PRS and estrogen receptor-specific PRS were evaluated. The odds of BC based on the PVs and PRS were estimated using penalized logistic regression. The results were combined with age-specific incidence rates to estimate 5-year and lifetime absolute risks of BC across percentiles of PRS by PV status and first-degree family history of BC. RESULTS: The estimated lifetime risks of BC among general-population noncarriers, based on 10th and 90th percentiles of PRS, were 9.1%-23.9% and 6.7%-18.2% for women with or without first-degree relatives with BC, respectively. Taking PRS into account, more than 95% of BRCA1, BRCA2, and PALB2 carriers had > 20% lifetime risks of BC, whereas, respectively, 52.5% and 69.7% of ATM and CHEK2 carriers without first-degree relatives with BC, and 78.8% and 89.9% of those with a first-degree relative with BC had > 20% risk. CONCLUSION: PRS facilitates personalization of BC risk among carriers of PVs in predisposition genes. Incorporating PRS into BC risk estimation may help identify > 30% of CHEK2 and nearly half of ATM carriers below the 20% lifetime risk threshold, suggesting the addition of PRS may prevent overscreening and enable more personalized risk management approaches.

Self-reported symptoms of arm lymphedema and health-related quality of life among female breast cancer survivors.

We examined cross-sectional associations between arm lymphedema symptoms and health-related quality of life (HRQoL) in the Health, Eating, Activity and Lifestyle (HEAL) Study. 499 women diagnosed with localized or regional breast cancer at ages 35-64 years completed a survey, on average 40 months after diagnosis, querying presence of lymphedema, nine lymphedema-related symptoms, e.g., tension, burning pain, mobility loss, and warmth/redness, and HRQoL. Analysis of covariance models were used to assess HRQoL scores in relation to presence of lymphedema and lymphedema-related symptoms. Lymphedema was self-reported by 137 women, of whom 98 were experiencing lymphedema at the time of the assessment. The most common symptoms were heaviness (52%), numbness (47%), and tightness (45%). Perceived physical health was worse for women reporting past or current lymphedema than those reporting no lymphedema (P-value < 0.0001). No difference was observed for perceived mental health (P-value = 0.31). Perceived physical health, stress, and lymphedema-specific HRQoL scores worsened as number of symptoms increased (P-values ≤ 0.01). Women reporting tension in the arm had lower physical health (P-value = 0.01), and those experiencing burning pain, tension, heaviness, or warmth/redness in the arm had lower lymphedema-specific HRQoL (P-values < 0.05). Treatment targeting specific lymphedema-related symptoms in addition to size/volume reduction may improve some aspects of HRQoL among affected women.

A Population-Based Study of Genes Previously Implicated in Breast Cancer.

BACKGROUND: Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants. METHODS: In a population-based case-control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed. RESULTS: Pathogenic variants in 12 established breast cancer-predisposition genes were detected in 5.03% of case patients and in 1.63% of controls. Pathogenic variants in BRCA1 and BRCA2 were associated with a high risk of breast cancer, with odds ratios of 7.62 (95% confidence interval [CI], 5.33 to 11.27) and 5.23 (95% CI, 4.09 to 6.77), respectively. Pathogenic variants in PALB2 were associated with a moderate risk (odds ratio, 3.83; 95% CI, 2.68 to 5.63). Pathogenic variants in BARD1, RAD51C, and RAD51D were associated with increased risks of estrogen receptor-negative breast cancer and triple-negative breast cancer, whereas pathogenic variants in ATM, CDH1, and CHEK2 were associated with an increased risk of estrogen receptor-positive breast cancer. Pathogenic variants in 16 candidate breast cancer-predisposition genes, including the c.657_661del5 founder pathogenic variant in NBN, were not associated with an increased risk of breast cancer. CONCLUSIONS: This study provides estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known breast cancer-predisposition genes in the U.S. population. These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes. (Funded by the National Institutes of Health and the Breast Cancer Research Foundation.).

Nanocage-Based N-Rich Metal-Organic Framework for Luminescence Sensing toward Fe3+ and Cu2+ Ions.

Luminescent metal-organic frameworks (LMOFs) as sensors showing highly efficient detection toward toxic heavy-metal ions are in high demand for human health and environmental protection. A novel nanocage-based N-rich LMOF (LCU-103) has been constructed and characterized. It is a 2-fold interpenetrating structure built from N-rich {Zn6(dttz)4} nanocages extended by N-donor ligand Hdpa [H3dttz = 4,5-di(1H-tetrazol-5-yl)-2H-1,2,3-triazole; Hdpa = 4,4'-dipyridylamine]. Notably, LCU-103 contains abundant N functional sites anchoring on both the windows of nanocages and the inner channels of the framework that can interact with metal ions and then recognize them. As a result, it can serve as a luminescent sensing material for detecting trace amounts of Fe3+ and Cu2+ ions with low limits of detection (LODs) of 1.45 and 1.66 µM, respectively, through a luminescent quenching mechanism. Meanwhile, LCU-103 as a LMOF sensor exhibits several advantages such as high sensitivity, appropriate selectivity (for Fe3+ in H2O), recycling stability, and fast response times in N,N-dimethylformamide. Moreover, LCU-103 also displays good luminescent quenching activity toward Fe3+ in H2O and a simulated 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid biological system with low LODs of 1.51 and 1.52 µM, respectively. LCU-103 test papers were further prepared to offer easy and real-time detection of Fe3+ and Cu2+ ions. Importantly, when density functional theory calculations and multiple experimental evidence, including X-ray photoelectron spectroscopy, UV-vis absorption, luminescence decay lifetimes, and quantum efficiencies, are combined, a preferred N-donor site and possible weak interaction sensing mechanism is also proposed to elucidate the quenching effect.

A Co-MOF-derived Co9S8@NS-C electrocatalyst for efficient hydrogen evolution reaction.

The exploitation of efficient hydrogen evolution reaction (HER) electrocatalysts has become increasingly urgent and imperative; however, it is also challenging for high-performance sustainable clean energy applications. Herein, novel Co9S8 nanoparticles embedded in a porous N,S-dual doped carbon composite (abbr. Co9S8@NS-C-900) were fabricated by the pyrolysis of a single crystal Co-MOF assisted with thiourea. Due to the synergistic benefit of combining Co9S8 nanoparticles with N,S-dual doped carbon, the composite showed efficient HER electrocatalytic activities and long-term durability in an alkaline solution. It shows a small overpotential of -86.4 mV at a current density of 10.0 mA cm-2, a small Tafel slope of 81.1 mV dec-1, and a large exchange current density (J 0) of 0.40 mA cm-2, which are comparable to those of Pt/C. More importantly, due to the protection of Co9S8 nanoparticles by the N,S-dual doped carbon shell, the Co9S8@NS-C-900 catalyst displays excellent long-term durability. There is almost no decay in HER activities after 1000 potential cycles or it retains 99.5% of the initial current after 48 h.