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Photoelectrochemical water splitting converts solar energy into clean hydrogen fuel. In this system, the preparation of high-quality photoanodes is essential for achieving efficient solar hydrolysis. Polymeric carbon nitride has emerged as a promising photocatalyst for solar water splitting due to its visible light absorption, suitable band edge positions and good chemical stability. However, considerable difficulties have been encountered in the preparation of robust and well-bonded carbon nitride films on conductive substrates. Herein, a combined strategy of electrophoresis and vapor deposition results in robust and high-performing carbon nitride film photoelectrodes with good bonding on substrates, suitable thickness for light absorption and enhanced charge separation and transfer abilities. The unique structure of the photoanode thus facilitates the oxidation of water and leads to an optimal photocurrent density of approximately 120 μA/cm2 at 1.23 VRHE. This work provides new insights for the preparation of polymeric carbon nitride film photoelectrodes, promoting the developments of photoelectric and photoelectrochemical applications based on carbon nitride.

Background: Early biologic response to endocrine therapy, such as changes in Ki67 labeling index (LI), has been suggested to predict long-term outcomes in hormone sensitive breast cancer. The addition of a CDK4/6 inhibitor to endocrine therapy has been shown to augment biological response in breast cancer. Pre-operative Endocrine Prognostic Index (PEPI) scores, generated based on post-treatment Ki67 LI, have been shown to predict patient outcomes. EndoPredict® is a multigene assay that predicts the risk of distant recurrence in patients with operable estrogen receptor (ER)-positive HER2-negative breast cancer. This study was conducted to evaluate the efficacy of the neoadjuvant endocrine therapy plus palbociclib versus neoadjuvant endocrine therapy plus placebo. Patients and Methods: This is a phase III randomized, double-blind study of neoadjuvant hormonal therapy plus palbociclib versus neoadjuvant hormonal therapy plus placebo in untreated pre/peri- and post-menopausal women with operable, hormone receptor-positive (ER and/or progesterone receptor), HER2-negative breast cancer. The other major inclusion criteria included tumor size ≥ 15mm, T1c-3N0-1, Ki67 LI ≥14% by central assessment, and no previous history of radiotherapy or systemic therapy for breast cancer. Patients were randomly assigned 1:1 to receive 16 weeks of hormonal therapy plus palbociclib or hormonal therapy plus placebo. Hormonal therapy consisted of letrozole for post-menopausal patients and tamoxifen plus LH-RH agonist for pre/peri-menopausal patients. The co-primary endpoints included PEPI score and EPclin Risk Score, a score combining EndoPredict® molecular score with clinical factors. These scores were sequentially analyzed on a modified intent-to-treat basis according to the gatekeeping procedure: if statistical significance was detected on the PEPI score, the statistical significance of EPclin Risk Score would be assessed. The sample size was 100 patients in each arm, which was calculated with < 5% type I error rate (two sided) and 80% power. Results: Between 16 July 2019 – 7 July 2021, 141 eligible patients were randomized from 25 participating institutes in Japan, Korea, Taiwan, Hong Kong and Australia. One hundred twenty-six patients completed the treatment duration and surgical samples were collected to evaluate endpoints. All randomized patients were evaluable for safety assessment. Randomization was well-balanced in terms of age, menopausal status and cancer stage. The proportion of patients who had a low, moderate, or high PEPI score was 15.2%, 50.0% and 34.8% in the hormonal therapy plus palbociclib arm and 13.3%, 55.0% and 31.7% in the hormonal therapy plus placebo arm, respectively. There was no statistically significant difference in PEPI score between two arms (one-sided p-value=0.563). The proportion of patients who had a high risk EPclin Risk Score seemed lower in the palbociclib arm than in the placebo arm (62.1% vs 68.3%) although hypothesis testing was not performed on EPclin Risk Score because statistical significance was not detected on the PEPI score. No new safety signals were found in the study. Permanent discontinuation from the study in association with adverse events was reported for 7 (9.7%) patients in the hormonal therapy plus palbociclib arm and for 0 patients in the hormonal therapy plus placebo arm. Conclusions: The addition of palbociclib to neoadjuvant hormonal therapy did not improve efficacy measured by PEPI score. In palbociclib arm, the rate of patients who had a high risk EPclin Risk Score after treatment was lower than in placebo arm. Translational researches are ongoing to analyze molecular changes by treatments. The role of chemotherapy after neoadjuvant therapy is under investigation. Clinical trial identification: NCT03969121 Funding: Pfizer Inc. Citation Format: Takayuki Ueno, Louis W.C. Chow, Wonshik Han, Chiun Sheng Huang, G Bruce Mann, Satoshi Morita, Hironori Haga, Elham Fakhrejahani, Takayuki Kobayashi, Kenichi Inoue, Mariko Tokiwa, Hirofumi Suwa, Tomoyuki Aruga, Sachiko Minamiguchi, Yosuke Yamada, Yuko Tanabe, Masahiro Takada, Toshinari Yamashita, Hiroji Iwata, Chi-Feng Chung, Sachiko Takahara, Eriko Tokunaga, Shigeru Imoto, Eun Sook Lee, Yasuaki Sagara, Jee Hyun Kim, Richard H DeBoer, Hyun-Ah Kim, Hung Wen Lai, Ming-Feng Hou, Michelle White, Yoshiko Umeyama. Neoadjuvant hormonal therapy plus palbociclib versus hormonal therapy plus placebo in women with operable, hormone sensitive and HER2-negative primary breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-09-01.

Diamond-like carbon (DLC) films containing single copper (Cu), single nickel (Ni) and double nickel/copper interlayers were fabricated on LY-12 aluminum (Al) alloy by electrodeposition. The influence of different interlayers on the microstructure, microhardness, friction and wear properties and electrochemical behavior of the films was investigated. The morphological results show that the porosity of DLC films was reduced and the particles were refined after the introduction of a double interlayer. Raman and X-ray photoelectron spectroscopy results confirm that the amorphous characteristics of DLC films containing nickel and copper interlayers were enhanced, and the content of sp3 carbon in the films was increased. Besides, an optimal microhardness of 210.67 HV was achieved due to the high sp3 carbon content of the double nickel/copper–DLC film. Meanwhile, the nickel/copper–DLC film possessed excellent wear resistance, which benefits from the synergistic effect of the copper and nickel interlayer. Nickel as the supporting layer and copper as the lubricating layer alleviated the wear and friction of the film. Simultaneously, the deposition of a double interlayer increased the density of the film, which further prevented the invasion of corrosion ions, so the film had superior electrochemical properties.

Survivin is a member of apoptosis inhibitor proteins that evokes cellular proliferation and inhibits apoptosis. However, the role of survivin in community-acquired pneumonia (CAP) patients remains to be firmly established. The aim of this cohort study was to evaluate the correlations of serum survivin with the severity and prognosis of CAP patients.This research included 470 eligible CAP patients. Serum fasting samples were drawn from patients, and serum survivin was measured by enzyme-linked immunosorbent assay (ELISA). Meanwhile, demographic characteristics and clinical information were collected. The prognosis of CAP patients was tracked.Serum survivin gradually decreased with elevated CAP severity scores. Additionally, the correlative analysis suggested that serum survivin was associated with many clinical characteristics. Furthermore, mixed linear and logistic regression models indicated that serum survivin was negatively associated with severity. After adjusting for confounding factors, logistic regression analyses found that lower serum survivin on admission elevated the risks of mechanical ventilation, vasoactive agent usage, longer hospital stays, ICU admission, and even death during hospitalization. Serum survivin in combination with CAP severity scores elevated the predictive capacities for severity and death in CAP patients compared with a single indicator.On admission, there are inverse dose-response associations of serum survivin with severity and poor prognosis in CAP patients, demonstrating that serum survivin may be involved in the pathophysiology process of CAP. Serum survivin may serve as a potential biomarker for disease evaluation and prognosis in CAP patients.

Adjuvant therapy; Breast cancer; Olaparib Terapia adyuvante; Cáncer de mama; Olaparib Teràpia adjuvant; Càncer de mama; Olaparib Background The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI −0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals. Funding for this work, which was conducted as a collaborative partnership among the Breast International Group, NRG Oncology, Frontier Science, AstraZeneca, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. (MSD), was provided by the National Institutes of Health (grant numbers: U10CA 180868, UG1CA 189867, and U10CA 180822) and by AstraZeneca as part of an alliance between AstraZeneca and MSD. Provision of olaparib and placebo was from AstraZeneca.

The electrocatalytic two-electron oxygen reduction reaction is an effective, safe and green approach to producing hydrogen peroxide, and ‘catalyst design’ for highly efficient hydrogen peroxide production has already been reported in various works. Specially, the modification of existing catalysts for two-electron oxygen reduction reaction through surface/interface engineering has huge potential to enhance further the catalytic performance of the catalysts. Moreover, a detailed overview on the research progress of carbon-based electrocatalysts through surface/interface engineering and their intrinsic reaction mechanism is helpful in realizing a comprehensive and systematic understanding of the latest progress in this field and further achieving highly efficient hydrogen peroxide electrosynthesis. Herein, fundamental aspects of the 2e−/4e− pathways of the oxygen reduction reaction are first introduced. Subsequently, a comprehensive summary of the current strategies for carbon-based catalyst modification through surface/interface engineering for high selectivity and yield of hydrogen peroxide production is presented. Finally, the prospects and challenges of hydrogen peroxide production with high efficiency and yield rate are presented, which should shed light on the industrial production and application of hydrogen peroxide.

Copper (Cu)-based materials have been extensively studied for nitrate (NO3 −) removal as an inexpensive and abundant electrocatalyst for water purification through the nitrate reduction reaction (NO3RR). However, it typically suffers from nitrite (NO2 −) accumulation due to high selectivity toward nitrite formation. To address this issue, the authors herein report a strategy of modifying copper nanowires with nickel (Ni) nanoparticles to improve the NO3RR performance. The nickel nanoparticles both facilitate electron transfer from nickel to copper and enhance the conversion of nitrite, thereby improving the overall removal of nitrate with a minimal yield of nitrite. Through a facile liquid-phase deposition process, the loading amount of nickel nanoparticles can be easily tailored by simply changing the concentration of precursors, and the best copper/nickel molar ratio for nitrate removal performance is 20. At this ratio, the material simultaneously delivers a high nitrate removal rate of 92.2% and low nitrite selectivity of only 2.2% at −0.9 V against the reversible hydrogen electrode, accompanied with superior stability for a continuous NO3RR. This study thus offers an efficient, stable and low-cost copper–nickel bimetallic catalyst for NO3RR.

As a type of titanate, the pseudobrookite (MTi2O5/M2TiO5) exhibits a low thermal expansion coefficient and thermal conductivity, as well as excellent dielectric and solar spectrum absorption properties. However, the pseudobrookite is unstable and prone to decomposing below 1200 °C, which limits the practical application of the pseudobrookite. In this paper, the high-entropy pseudobrookite ceramic is synthesized for the first time. The pure high-entropy (Mg,Co,Ni,Zn)Ti2O5 with the pseudobrookite structure and the biphasic high-entropy ceramic composed of the high-entropy pseudobrookite (Cr,Mn,Fe,Al,Ga)2TiO5 and the high-entropy spinel (Cr,Mn,Fe,Al,Ga,Ti)3O4 are successfully prepared by the in-situ solid-phase reaction method. The comparison between the theoretical crystal structure of the pseudobrookite and the aberration-corrected scanning transmission electron microscopy (AC-STEM) images of high-entropy (Mg,Co,Ni,Zn)Ti2O5 shows that the metal ions (M and Ti ions) are disorderly distributed at the A site and the B site in high-entropy (Mg,Co,Ni,Zn)Ti2O5, leading to an unprecedentedly high configurational entropy of high-entropy (Mg,Co,Ni,Zn)Ti2O5. The bulk high-entropy (Mg,Co,Ni,Zn)Ti2O5 ceramics exhibit a low thermal expansion coefficient of 6.35×10−6 K−1 in the temperature range of 25–1400 °C and thermal conductivity of 1.840 W·m−1·K−1 at room temperature, as well as the excellent thermal stability at 200, 600, and 1400 °C. Owing to these outstanding properties, high-entropy (Mg,Co,Ni,Zn)Ti2O5 is expected to be the promising candidate for high-temperature thermal insulation. This work has further extended the family of different crystal structures of high-entropy ceramics reported to date.

While radiotherapy remains the cornerstone of head and neck cancer treatment, oral mucositis is a very serious side effect, especially grade III/IV oral mucositis. Oral mucositis not only seriously reduces the quality of life of patients, but also affects the ongoing treatment of patients. Use of honey for the remediation of oral mucositis promising, but clinically controversial. Therefore, to further ascertain its role in oral mucositis, an extensive literature search was performed in the Pubmed, Embase and Cochrane databases. Thirteen randomized controlled trials with 899 patients were included in the analysis. Pooled Odds ratio with 95% confidence intervals was analyzed. The results show that a significantly fewer number of patients treated with honey experienced grade III/IV oral mucositis after radiotherapy (OR 0.24, 95% CI 0.13–0.44, p < 0.001). The administration of honey concurrently with radiotherapy decreased the rate of graded III/IV oral mucositis. Thus, the use of honey during radiotherapy may represent a feasible strategy for preserving tolerance.

Despite theoretical accounts asserting the importance of children for the wellbeing of individuals as they age, research evidence suggests that children may be inconsequential when it comes to loneliness. Yet, there is reason to expect some subgroups may be more vulnerable to the impact of childlessness than others and this may also differ depending on the type of loneliness being assessed. This paper addresses the relationship between childlessness and social and emotional loneliness in middle and later life, including differential vulnerability associated with age, gender and marital/partner status. The study drew on data from three waves (2007, 2012 and 2018) of the Canadian General Social Survey for a nationally representative sample of adults aged 45 and older (N = 49,892). In general, childlessness assumed greater importance with regard to social than emotional loneliness. Women reported lower levels of social loneliness in conjunction with childlessness than men. Further, childlessness was associated with higher levels of overall and social loneliness among older than middle-aged adults. Fewer interactions were evident between marital/partner status and childlessness. Among women specifically, those who were co-habiting, separated/divorced or never married reported lower levels of social loneliness than their married counterparts. In contrast, childlessness was linked to greater emotional loneliness only among separated/divorced men and widowed women. Overall, our results suggest that having children available does matter for feelings of loneliness in middle and later life but that the relationship varies and is contingent on the social contexts (age, gender, marital/partner status) and the type of loneliness (social, emotional) involved.

Cloud Manufacturing (CMfg) merging concepts such as the Industry Internet of Things has been paving the road of Industry 4.0. However, as the cornerstone of CMfg, cross-domain data acquisition from heterogeneous data sources faces the issues of too many low-quality data, dumb machines and engineering knowledge loss. Hence, this paper proposed an ontology-based data acquisition for the CMfg which is built on a cloud-fog-edge architecture. Special edge node with a recognition model is designed to collect data from dump machines; fog nodes used multi-threaded fog computing are placed at the center to connect cloud servers, and machines / edge nodes; and an acquisition ontology in cloud servers is used to produce machine template and store cross-domain semantic knowledge. To validate the proposed data acquisition system, we compared vital metrics like upload times, floating point operations, and data storage requirements to a conventional data acquisition system, and have also conducted preliminary evaluations of the system in two real-word factory testbeds, which show that the FADA can save 2.9 TB of disk space per day, and reduce the server's processing time by 184.8ms per time over the conventional data acquisition system(CDAS) when 20,000 fog nodes simultaneously access the server.

The discovery of early diagnosis and prognostic markers for breast cancer can significantly improve survival and reduce mortality. LSM1 is known to be involved in the general process of mRNA degradation in complexes containing LSm subunits, but the molecular and biological functions in breast cancer remain unclear. Here, the expression of LSM1 mRNA in breast cancer was estimated using The Cancer Genome Atlas (TCGA), Oncomine, TIMER and bc-GenExMiner databases. We found that functional LSM1 inactivation caused by mutations and profound deletions predicted poor prognosis in breast cancer (BRCA) patients. LSM1 was highly expressed in both BRCA tissues and cells compared to normal breast tissues/cells. High LSM1 expression is associated with poorer overall survival and disease-free survival. The association between LSM1 and immune infiltration of breast cancer was assessed by TIMER and CIBERSORT algorithms. LSM1 showed a strong correlation with various immune marker sets. Most importantly, pharmacogenetic analysis of BRCA cell lines revealed that LSM1 inactivation was associated with increased sensitivity to refametinib and trametinib. However, both drugs could mimic the effects of LSM1 inhibition and their drug sensitivity was associated with MEK molecules. Therefore, we investigated the clinical application of LSM1 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of breast cancer.

CDK4 is highly expressed and correlated with poor prognosis and decreased survival in advanced NB. Seeking a regimen that selectively targets CDK4 degradation is a potentially promising therapeutic strategy relative to conventional CDK4 inhibitors.In this work, we determined that autophagy as a new pathway for the degradation of CDK4. Firstly, autophagic degradation of CDK4 is critical for NVP-BEZ235-induced G0/G1 arrest and growth inhibition via the blockade of autophagy-related gene Beclin1. Secondly, we observed the first evidence that the p62 binds to CDK4 and then enter autophagolysosome to degradate CDK4 in a CTSB-dependent manner in NVP-BEZ235 treated NB cells. Analogous results regarding the interaction p62 with CDK4 were observed in NVP-BEZ235 treated neuroblastoma xenograft mouse model. These results not only established the pivotal role of the autophagy pathway in CDK4 turnover but also suggest the potential application of NVP-BEZ235 or other drugs via the therapeutic modulation of autophagic degradation of CDK4 protein in NB.

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Supplementary Figure S1. LocusZoom regional association plots for the seven new cross-cancer loci that were > 1 Mb from known index SNPs. Supplementary Figure S2A-B. Box plots showing eQTL associations between (A) rs9375701 and L3MBTL3 in normal breast and prostate tissues and (B) rs8037137 and RCCD1 in normal breast and ovarian tissues. Supplementary Figure S3. Interactions between BCL2L11 and the 32 Biocarta "Death Pathway" genes. Interactions were identified using the GeneMania server. Circles contain gene names, lines represent interactions, and the color of the line indicates a specific type of interaction as listed in the legend.