bluuebunny/crossref_metadata_2025 huggingface dataset:
Noble Gas Anions: An Overview of Strategies and Bonding Motifs
Authors: Borocci Stefano , Grandinetti Felice , Sanna Nico , Zazza Costantino
Published: May 2024

This review article aims to provide an overview of the strategies employed to prepare noble gas anions under different environments and experimental conditions, and of the bonding motifs typically occurring in these species. Observed systems include anions fixed into synthesized salts, detected in the gas phase or in high‐pressure devices. The major role of the theoretical calculations is also highlighted, not only in support of the experiments, but also as effective in predicting still unreported species. The chemistry of noble gas anions overall appears as a varied and rich paint, offering fascinating opportunities for both experimentalists and theoreticians.
Challenges and Perspectives for Direct Recycling of Electrode Scraps and End‐of‐Life Lithium‐ion Batteries
Authors: Hayagan Neil , Gaalich Insaf , Loubet Philippe , Croguennec Laurence , Aymonier Cyril , Philippot Gilles , Olchowka Jacob
Published: May 2024

The growing demand and production of lithium‐ion batteries (LIBs) have led to a critical concern regarding their resources and end‐of‐life management. Consequently, LIB recycling has emerged as a prominent topic in academia and in industries, driven by new worldwide governmental regulations and the increasing gap between the supply and demand of critical and strategic raw materials. Widely considered as a more sustainable and cheaper recycling method compared to pyrometallurgy and hydrometallurgy, direct recycling currently grabs the spotlight. This perspective provides insights and outlooks on the chemical and technological challenges of the innovative direct recycling approach for LIBs, addressing both the production scraps and batteries at their end‐of‐life (EOL). Technological advancements, changes in battery chemistry, along with the LIB market dynamics and collaborations between battery makers and recyclers, are key drivers of LIB waste recycling. While production scraps lend themselves well to direct recycling, EOL batteries encounter challenges in adopting this novel recycling technology. Besides, the need to assess novel direct recycling processes using Life Cycle Assessment (LCA) is also important for identifying eco‐design strategies and optimizing the processes, leading to a more sustainable energy storage system.
A review of the current treatment methods for retroperitoneal fibrosis with obstructive uropathy
Authors: Carey Charles , Gurumurthy Gerard , Napier‐Hemy Richard , Zelhof Bachar
Published: May 2024

Introduction and aims

Retroperitoneal fibrosis (RPF) is a fibroinflammatory disease in which patients may suffer obstructive uropathy (OU). The optimum treatment strategy for RPF with secondary OU is currently unclear, and the aim of this literature review is to assess the methods used to treat this patient cohort.

Methods

Medline, Embase, Cinahl, the Cochrane Library and PubMed were systematically searched to find studies assessing treatment outcomes in this patient cohort. After reviewing the studies' titles, abstracts and full texts, 12 were found that matched our search aims. Data from these publications were analysed and reported.

Results

The demographic and symptomatic features of patients across the 12 studies were representative of the general RPF population. No randomised control trials (RCTs) were found, and just one study formally compared outcomes between patients who underwent different treatment strategies. Many of the studies concluded that using medical and surgical methods in combination led to positive outcomes; whereas, others found positive outcomes following a variety of regimens. Many studies also highlighted, however, that significant minorities required further treatment after initial therapy. Conclusions regarding optimum treatment methods were limited as most publications did not formally compare outcomes following different strategies and had an observational study design.

Conclusion

Although positive outcomes were commonly seen following medical, surgical and a combination of treatments, the literature currently lacks research formally comparing outcomes after assigning specific treatment protocols to groups of RPF patients. More research is therefore required to determine how to best manage RPF leading to secondary OU.
The role of upfront lenalidomide maintenance for primary central nervous system lymphoma following first‐line methotrexate treatment: A retrospective study
Authors: Zhang Yan , Wang Wei , Zhao Danqing , Chong Wei , Chen Chao , Zhang Wei , Zhou Daobin
Published: May 2024

Background

Consolidation therapy improves the duration of response among patients with primary central nervous system lymphoma (PCNSL). Lenalidomide maintenance has shown encouraging results in older patients with PCNSL. Herein, we performed a retrospective, single‐center analysis to evaluate the effect of lenalidomide maintenance on the duration of response in patients with newly‐diagnosed PCNSL.

Methods

Sixty‐nine adult patients with PCNSL who achieved complete remission or partial remission (PR) after induction therapy were enrolled. The median age of patients was 58.0 years. The maintenance group (n = 35) received oral lenalidomide (25 mg/day) for 21 days, every 28 days for 24 months; the observation group did not undergo any further treatment.

Results

After a median follow‐up of 32.6 months, the maintenance group experienced fewer relapse events. However, the median progression‐free survival (PFS) was similar between groups (36.1 vs. 30.6 months; hazard ratio, 0.78; 95% confidence interval, 0.446). Lenalidomide maintenance significantly improved PFS and overall survival (OS) only among patients who experienced PR after induction. The median duration of lenalidomide maintenance was 18 months; lenalidomide was well tolerated and minimally impacted the quality of life.

Conclusions

The present study was the first to evaluate lenalidomide maintenance as a frontline treatment among patients with PCNSL, PFS and OS did not improve, although the safety profile was satisfactory.
Kaempferol Derivatives from Hippophae rhamnoides Linn. Ameliorate H2O2‐Induced Oxidative Stress in SH‐SY5Y Cells by Upregulating Nrf2
Authors: Ding Jin , Tie Fangfang , Dong Qi , Hu Na , Wang Honglun
Published: May 2024

As a medicinal and edible resource, Hippophae rhamnoides Linn. subsp. sinensis Rousi is rich in bioactive secondary metabolites, including flavonoids and their derivatives, which offer protective effects against oxidative damage. This study reported the isolation of three new kaempferol derivatives from the seed residue of H. rhamnoides – Hippophandine A, B, and C (compounds 1–3). Their structures were elucidated by high‐resolution electrospray ionization mass spectrometry (HR‐ESI‐MS), nuclear magnetic resonance (NMR), and chemical analyses. The compounds were evaluated for their ability to mitigate hydrogen peroxide (H2O2)‐induced cell death in SH‐SY5Y cells. The results elucidated that Hippophandine A−C at concentrations of 1, 5, and 10 μM reduced the levels of malondialdehyde (MDA) and increased the activity of antioxidative enzymes, such as superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). Furthermore, they significantly altered the protein expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) and its downstream heme oxygenase‐1 (HO‐1), which is an indicator of redox detection in H2O2‐induced SH‐SY5Y.
A hybrid construct of decellularized matrix and fibrin for differentiating adipose stem cells into insulin‐producing cells, an optimized in vitro assessment
Authors: Bozorgi Azam , Khazaei Mohammad Rasool , Bozorgi Maryam , Khazaei Mozafar
Published: May 2024

The generation of insulin‐producing cells (IPCs) is an attractive approach for replacing damaged β cells in diabetic patients. In the present work, we introduced a hybrid platform of decellularized amniotic membrane (dAM) and fibrin encapsulation for differentiating adipose tissue‐derived stem cells (ASCs) into IPCs. ASCs were isolated from healthy donors and characterized. Human AM was decellularized, and its morphology, DNA, collagen, glycosaminoglycan (GAG) contents, and biocompatibility were evaluated. ASCs were subjected to four IPC differentiation methods, and the most efficient method was selected for the experiment. ASCs were seeded onto dAM, alone or encapsulated in fibrin gel with various thrombin concentrations, and differentiated into IPCs according to a method applying serum‐free media containing 2‐mercaptoethanol, nicotinamide, and exendin‐4. PDX‐1, GLUT‐2 and insulin expression were evaluated in differentiated cells using real‐time PCR. Structural integrity and collagen and GAG contents of AM were preserved after decellularization, while DNA content was minimized. Cultivating ASCs on dAM augmented their attachment, proliferation, and viability and enhanced the expression of PDX‐1, GLUT‐2, and insulin in differentiated cells. Encapsulating ASCs in fibrin gel containing 2 mg/ml fibrinogen and 10 units/ml thrombin increased their differentiation into IPCs. dAM and fibrin gel synergistically enhanced the differentiation of ASCs into IPCs, which could be considered an appropriate strategy for replacing damaged β cells.
The Role of AI in Drug Discovery
Authors: Abbas M. K. G. , Rassam Abrar , Karamshahi Fatima , Abunora Rehab , Abouseada Maha
Published: May 2024

The emergence of Artificial Intelligence (AI) in drug discovery marks a pivotal shift in pharmaceutical research, blending sophisticated computational techniques with conventional scientific exploration to break through enduring obstacles. This review paper elucidates the multifaceted applications of AI across various stages of drug development, highlighting significant advancements and methodologies. It delves into AI′s instrumental role in drug design, polypharmacology, chemical synthesis, drug repurposing, and the prediction of drug properties such as toxicity, bioactivity, and physicochemical characteristics. Despite AI′s promising advancements, the paper also addresses the challenges and limitations encountered in the field, including data quality, generalizability, computational demands, and ethical considerations. By offering a comprehensive overview of AI′s role in drug discovery, this paper underscores the technology‘s potential to significantly enhance drug development, while also acknowledging the hurdles that must be overcome to fully realize its benefits.
Single‐Operator Left atrial appendage Occlusion utilizing Conscious sedation TEE, Lack of Outpatient pre‐imaging, and Same‐day Expedited discharge (SOLO‐CLOSE): A comparison with conventional approach
Authors: Golzarian Hafez , Pasley Benjamin A. , Shah Sidra R. , Thiel Arielle M. , Knous Mallory , Kleman Anna C. , Saum Jamie L. , Hempfling Gerri L. , Otto Michael , Otto Todd , Racer Lisa , Martz Denise , Gemmel David J. , Laird Amanda D. , Cole William C. , Parsa Prabhakar , Imm Craig , Patel Sandeep M.
Published: May 2024

Background

Left atrial appendage occlusion (LAAO) with WATCHMAN currently requires preprocedural imaging, general anesthesia, and inpatient overnight admission. We sought to facilitate simplification of LAAO.

Aims

We describe and compare SOLO‐CLOSE (single‐operator LAA occlusion utilizing conscious sedation TEE, lack of outpatient pre‐imaging, and same‐day expedited discharge) with the conventional approach (CA).

Methods

A single‐center retrospective analysis of 163 patients undergoing LAAO between January 2017 and April 2022 was conducted. The SOLO‐CLOSE protocol was enacted on December 1, 2020. Before this date, we utilized the CA. The primary efficacy endpoint was defined as successful LAAO with ≤5 mm peri‐device leak at time of closure. The primary safety endpoint was the composite incidence of all‐cause deaths, any cerebrovascular accident (CVA), device embolization, pericardial effusion, or major postprocedure bleeding within 7 days of the index procedure. Procedure times, 7‐day readmission rates, and cost analytics were collected as well.

Results

Baseline characteristics were similar in both cohorts. Congestive heart failure (37.5% vs. 11.1%) and malignancy (28.8% vs. 12.5%) were higher in SOLO‐CLOSE. Median CHA2D2SVASc score was 5 in both cohorts. The primary efficacy endpoint was met 100% in both cohorts. Primary safety endpoint was similar between cohorts (p = 0.078). Mean procedure time was 30 min shorter in SOLO‐CLOSE (p < 0.01). Seven‐day readmissions for SOLO‐CLOSE was zero. After SOLO‐CLOSE implementation, there was a 188% increase in positive contribution margin per case.

Conclusions

The SOLO‐CLOSE methodology offers similar efficacy and safety when compared to the CA, while improving clinical efficiency, reducing procedural times, and increasing economic benefit.
Decades of stability of conjunctival vascular malformations in two patients
Authors: Matsuo Toshihiko , Tanaka Takehiro , Kimata Yoshihiro
Published: May 2024

Key Clinical Message

Conjunctival hemangioma and lymphangioma are rare and their long‐term follow‐up description has been scarce. In our two patients, conjunctival vascular and lymphatic malformations remained stable in decades and could be observed without treatment.

A 65‐year‐old woman with diabetic retinopathy underwent glaucoma surgery to construct a filtering bleb adjacent to conjunctival hemangioma, and showed bleb function and stable hemangioma for a decade. A 1.5‐year‐old girl with right eye lid and cheek swelling by orbital to facial lymphangioma was followed for visual acuity development. Conjunctival lymphangioma was stable in 20 years.
A Review on Fe2O3‐Based Catalysts for Toluene Oxidation: Catalysts Design and Optimization with the Formation of Abundant Oxygen Vacancies
Authors: Zhang Ruoqun , He Hongzhe , Tang Yuneng , Zhang Zhicheng , Zhou Hailiang , Yu Jianglong , Zhang Lian , Dai Baiqian
Published: May 2024

Volatile organic compounds (VOCs) are typical pollutants with hazards for humans and the environment, which can be efficiently mitigated by catalytic combustion. Fe2O3‐based catalysts are a promising choice due to their low cost and strong redox ability. Several attempts have been made to promote the catalytic performance for Fe2O3‐based catalysts at low temperatures. This review summarizes the research progress on Fe2O3‐based catalysts for the oxidation of toluene, one of the most common and harmful VOC. Firstly, the structural properties and catalytic performances for Fe2O3‐based catalysts have been summarized, and the reaction mechanisms for toluene oxidation on the surface of Fe2O3‐based catalysts were detailed to comprehend the role of oxygen vacancies. Then, the modification for single Fe2O3 catalysts, including synthesis parameters, structure and morphology control, is introduced to reveal the correlation between physicochemical properties of catalysts and their activity for toluene oxidation. In addition, composite Fe2O3 catalysts, which can promote catalytic performance significantly by the synergetic effect between different components, were presented in detail. Moreover, waste‐derived Fe2O3 catalysts with sustainable merit as converting waste into worth have been discussed. Finally, the advanced machine learning tools, which are helpful in accelerating catalyst design, configuration optimization and reactivity prediction, have been introduced as an emerging research opportunity for the future.
Ionic Liquids Boost Anthraquinone Hydrogenation over Pd‐based Bimetallic Pincer Catalysts
Authors: Li Xiaolei , Zhang Tiantong , Wang Fuying , Peng Mao , Zhang Jinli , Gu Chengzhi , Li Xiaoyan , Li Wei
Published: May 2024

A series of bimetallic‐ionic liquid (IL) pincer catalysts Pd−M@IL were synthesized using low Pd‐loading amount (0.3 %) and adopting six kinds of ion liquids with the cation containing the imidazole ring, and then evaluated the catalytic activities toward 2‐ethylanthraquinone hydrogenation reaction with the purpose to produce H2O2. Under the reaction conditions of 60 °C, 0.30 MPa and 15 min reaction time, over the catalysts Pd−La@[BMIm]Ac/alu and Pd−La@[VBIM]Br/alu achieved high hydrogenation efficiency(9.4 g/L and 8.5 g/L) but also high selectivity toward the active anthraquinone (98.9 % and 99.6 %). Through characterizations of STEM, TPD, in‐situ XPS, etc., it illustrates that the pincer catalysts Pd−La@[BMIm]Ac/alu and Pd−La@[VBIM]Br/alu have much better dispersity than the bimetallic Pd−La/alu, these two ionic liquids of [BMIm]Ac and [VBIM]Br provide different local environment around Pd−La sites, which in turn modulate the catalytic activity of the pincer‐catalysts toward anthraquinone hydrogenation. DFT calculations disclose the unique electron transfer between ILs ([BMIm]Ac and [VBIM]Br) and Pd−La clusters and subsequent changes of energy barriers for anthraquinone hydrogenation. The work illuminates a facile strategy to design novel hydrogenation catalysts through combining the pincer microenvironment partially encapsulated by the cation and the anion of ionic liquids with the internal bimetallic sites.
Association between plasma growth differentiation factor 15 levels and pre‐eclampsia in China
Authors: Xu Shuhong , Lu Yicheng , Yao Mengxin , Yang Zhuoqiao , Chen Yan , Ding Yaling , Xiao Yue , Liang Fei , Qian Jiani , Ma Jinchun , Liu Songliang , Yan Shilan , Yin Jieyun , Ma Qiuping
Published: May 2024

Background

Growth differentiation factor‐15 (GDF‐15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association between GDF‐15 and pre‐eclampsia (PE).

Method

The study involved 299 pregnant women, out of which 236 had normal pregnancies, while 63 participants had PE. Maternal serum levels of GDF‐15 were measured by using enzyme‐linked immunosorbent assay kits and then translated into multiple of median (MOM) to avoid the influence of gestational week at blood sampling. Logistic models were performed to estimate the association between GDF‐15 MOM and PE, presenting as odd ratios (ORs) and 95% confidence intervals (CIs).

Results

MOM of GDF‐15 in PE participants was higher compared with controls (1.588 vs. 1.000, p < 0.001). In the logistic model, pregnant women with higher MOM of GDF‐15 (>1) had a 4.74‐fold (95% CI = 2.23–10.08, p < 0.001) increased risk of PE, adjusted by age, preconceptional body mass index, gravidity, and parity.

Conclusions

These results demonstrated that higher levels of serum GDF‐15 were associated with PE. GDF‐15 may serve as a biomarker for diagnosing PE.
sAPPα Peptide Promotes Damaged Microglia to Clear Alzheimer's Amyloid‐β via Restoring Mitochondrial Function
Authors: Tang Yingqi , Wang Yangang , Gao Ziran , Li Jiayi , Zhang Lijia , Shi Haoting , Dong Jingwen , Song Shipeng , Qian Chenggen
Published: May 2024

Alzheimer's disease (AD) is an age‐related neurodegenerative disease with amyloid‐β (Aβ) deposition as the main pathological feature. It's an important challenge to find new ways to clear Aβ from the brain. The soluble amyloid precursor protein α (sAPPα) is a neuroprotective protein and can attenuate neuronal damage, including toxic Aβ. However, the regulatory role of sAPPα in non‐neuronal cells, such as microglia, is less reported and controversial. Here, we showed that sAPPα promoted the phagocytosis and degradation of Aβ in both normal and damaged microglia. Moreover, the function of damaged microglia was improved by the sAPPα through normalizing mitochondrial function. Furthermore, the results of molecular docking simulation showed that sAPPα had a good affinity with Aβ. We preliminarily reveal that sAPPα is similar to antibodies and can participate in the regulation of microglia phagocytosis and degradation of Aβ after binding to Aβ. sAPPα is expected to be a mild and safe peptide drug or drug carrier for AD.
Two‐Phase Electrosynthesis of Dihydroxycoumestans: Discovery of a New Scaffold for Topoisomerase I Poison
Authors: Chen Yue‐Xi , Wu Shanchao , Shen Xiang , Xu Dong‐Fang , Wang Qian , Ji Su‐Hui , Zhu Huajian , Wu Ge , Sheng Chunquan , Cai Yun‐Rui
Published: May 2024

Coumestan represents a biologically relevant structural motif distributed in a number of natural products, and the rapid construction of related derivatives as well as the characterization of targets would accelerate lead compound discovery in medicinal chemistry. In this work, a general and scalable approach to 8,9‐dihydroxycoumestans via two‐electrode constant current electrolysis was developed. The application of a two‐phase (aqueous/organic) system plays a crucial role for success, protecting the sensitive o‐benzoquinone intermediates from over‐oxidation. Based on the structurally diverse products, a primary SAR study on coumestan scaffold was completed, and compound 3 r exhibited potent antiproliferative activities and a robust topoisomerase I (Top1) inhibitory activity. Further mechanism studies demonstrates that compound 3 r was a novel Top1 poison, which might open an avenue for the development of Top1‐targeted antitumor agent.
Photoredox/Bismuth Relay Catalysis Enabling Reductive Alkylation of Nitroarenes with Aldehydes
Authors: Li Jinlian , Chen Xing , Xie Shenxia , Wang Huabing , Mo Jiayu , Huang Huawen
Published: May 2024

The effective transition metal‐free photoredox/bismuth dual catalytic reductive dialkylation of nitroarenes with benzaldehydes has been reported. The nitroarene reduction through visible light‐driven photoredox catalysis was integrated with subsequent reductive dialkylation of anilines under bismuth catalysis to enable the cascade reductive alkylation of nitroarenes with carbonyls. Salient features of this relay catalysis system include mild reaction conditions, no requirement for transition metal catalysts, easy handling, step‐economy, and high selectivity.
A Broadened Class of Donor‐Acceptor Stacked Macrometallacyclic Adducts of Different Coinage Metals
Authors: Lu Zhou , Luciani Lorenzo , Li Shan , Nesterov Vladimir N. , Zuccaccia Cristiano , Macchioni Alceo , Fripp Jacob L. , Zhang Weijie , Omary Mohammad A. , Galassi Rossana
Published: May 2024

A yet‐outstanding supramolecular chemistry challenge is isolation of novel varieties of stacked complexes with finely‐tuned donor‐acceptor bonding and optoelectronic properties, as herein reported for binary adducts comprising two different cyclic trinuclear complexes (CTC@CTC’). Most previous attempts focused only on 1–2 factors among metal/ligand/substituent combinations, resulting in heterobimetallic complexes. Instead, here we show that, when all 3 factors are carefully considered, a broadened variety of CTC@CTC’ stacked pairs with intuitively‐enhanced intertrimer coordinate‐covalent bonding strength and ligand‐ligand/metal‐ligand dispersion are attained (dM–M’ 2.868(2) Å; ΔE>50 kcal/mol, an order of magnitude higher than aurophilic/metallophilic interactions). Significantly, CTC@CTC’ pairs remain intact/strongly‐bound even in solution (Keq 4.67×105 L/mol via NMR/UV‐vis titrations), and the gas phase (mass spectrometry revealing molecular peaks for the entire CTC@CTC’ units in sublimed samples), rather than simple co‐crystal formation. Photo‐/electro‐luminescence studies unravel metal‐centered phosphorescence useful for novel all metal‐organic light‐emitting diodes (MOLEDs) optoelectronic device concepts. This work manifests systematic design of supramolecular bonding and multi‐faceted spectral properties of pure metal‐organic macrometallacyclic donor/acceptor (inorganic/inorganic) stacks with remarkably‐rich optoelectronic properties akin to well‐established organic/organic and organic/inorganic analogues.
Streptavidin‐Biotin Complexes as Tools for Modulating an Important DNA Epigenetic Modification†
Authors: Liu Yongjie , Xu Xinyan , Liu Xingyu , Xiong Wei , Qi Qianqian , Zhang Yuanyuan , Hou Jinxuan , Tian Tian , Zhou Xiang
Published: May 2024

Comprehensive Summary

DNA 5‐formylcytosine (5fC) is a prominent epigenetic modification within biological systems. Recent investigations have shed light on its pivotal role in governing cell fate, gene expression, and disease pathways. However, our comprehension of the precise control of the 5fC site structure to influence its functionality remains limited. In this study, we have successfully achieved precise control over 5fC activity by harnessing the interaction between streptavidin and biotin. This research underscores the potential application of interactions between biomacromolecules and small molecules in advancing the field of DNA epigenetic functional regulation.
Breast cancer incidence and mortality by metabolic syndrome and obesity: The Women’s Health Initiative
Authors: Chlebowski Rowan T. , Aragaki Aaron K. , Pan Kathy , Simon Michael S. , Neuhouser Marian L. , Haque Reina , Rohan Thomas E. , Wactawski‐Wende Jean , Orchard Tonya S. , Mortimer Joanne E. , Lane Dorothy , Kaunitz Andrew M. , Desai Pinkal , Wild Robert A. , Barac Ana , Manson JoAnn E.
Published: May 2024

Background

In the Women’s Health Initiative (WHI) randomized trial, dietary intervention significantly reduced breast cancer mortality, especially in women with more metabolic syndrome (MetS) components. Therefore, this study investigated the associations of MetS and obesity with postmenopausal breast cancer after long‐term follow‐up in the WHI clinical trials.

Methods

A total of 68,132 postmenopausal women, without prior breast cancer and with normal mammogram, were entered into WHI randomized clinical trials; 63,330 women with an entry MetS score comprised the study population. At entry, body mass index (BMI) was determined; MetS score (0, 1–2, and 3–4) included the following: (1) high waist circumference (≥88 cm), (2) high blood pressure (systolic ≥130 mm Hg and/or diastolic ≥85 mm Hg, or hypertension history), (3) high‐cholesterol history, and (4) diabetes history. Study outcomes included breast cancer incidence, breast cancer mortality, deaths after breast cancer, and results by hormone receptor status.

Results

After a >20‐year mortality follow‐up, a higher MetS score (3–4), adjusted for BMI, was significantly associated with more poor prognosis, estrogen receptor (ER)–positive, progesterone receptor (PR)–negative cancers (p = .03), 53% more deaths after breast cancer (p < .001), and 44% higher breast cancer mortality (p = .03). Obesity status, adjusted for MetS score, was significantly associated with more good prognosis, ER‐positive, PR‐positive cancers (p < .001), more total breast cancers (p < .001), and more deaths after breast cancer (p < .001), with higher breast cancer mortality only in women with severe obesity (BMI, ≥35 kg/m2; p < .001).

Conclusions

MetS and obesity status have independent, but differential, adverse associations with breast cancer receptor subtypes and breast cancer mortality risk. Both represent separate targets for breast cancer prediction and prevention strategies.
Dealing With Variable Drug Exposure Due to Variable Hepatic Metabolism: A Proof‐of‐Concept Application of Liquid Biopsy in Renal Impairment
Authors: Rostami‐Hodjegan Amin , Al‐Majdoub Zubida M. , von Grabowiecki Yannick , Yee Ka Lai , Sahoo Sudhakar , Breitwieser Wolfgang , Galetin Aleksandra , Gibson Christopher , Achour Brahim
Published: May 2024

Precision dosing strategies require accounting for between‐patient variability in pharmacokinetics (PK), affecting drug exposure, and in pharmacodynamics (PD), affecting response achieved at the same drug concentration at the site of action. Although liquid biopsy for assessing different levels of molecular drug targets has yet to be established, individual characterization of drug elimination pathways using liquid biopsy has recently been demonstrated. The feasibility of applying this approach in conjunction with modeling tools to guide individual dosing remains unexplored. In this study, we aimed to individualize physiologically‐based pharmacokinetic (PBPK) models based on liquid biopsy measurements in plasma from 25 donors with different grades of renal function who were previously administered oral midazolam as part of a microdose cocktail. Virtual twin models were constructed based on demographics, renal function, and hepatic expression of relevant pharmacokinetic pathways projected from liquid biopsy output. Simulated exposure (AUC) to midazolam was in agreement with observed data (AFE = 1.38, AAFE = 1.78). Simulated AUC variability with three dosing approaches indicated higher variability with uniform dosing (14‐fold) and stratified dosing (13‐fold) compared with individualized dosing informed by liquid biopsy (fivefold). Further, exosome screening revealed mRNA expression of 532 targets relevant to drug metabolism and disposition (169 enzymes and 361 transporters). Data related to these targets can be used to further individualize PBPK models for pathways relevant to PK of other drugs. This study provides additional verification of liquid biopsy‐informed PBPK modeling approaches, necessary to advance strategies that seek to achieve precise dosing from the start of treatment.
Photochemical Synthesis and Ring‐Opening of Aziridines and Epoxides: State‐of‐the‐Art
Authors: Furniel Lucas G. , Corrêa Arlene G.
Published: May 2024

The development of greener methods for the preparation of three‐membered rings has increased in the last decade, not only due to their biological activity but also to the ring strain of those heterocycles that make them useful precursors of more complex molecules. In this work, the visible‐light‐promoted synthesis and ring‐opening of aziridines and epoxides, reported in the last five years, were reviewed. Both homogeneous and heterogeneous catalysts were discussed and, in addition, the plausible mechanism pathways were highlighted.
Does internal control improve enterprise environmental, social, and governance information disclosure? Evidence from China
Authors: Yan Jialin , Hu Haibo , Hu Yiruo
Published: May 2024

Environmental, social, and governance (ESG) is a relatively new concept that emphasizes how to contribute to creating sustainable businesses. However, research on factors that influence ESG development is insufficient. This study explores how internal control influence enterprise ESG information disclosure, using 2009–2021 data from China's A‐share listed companies. The findings show a substantial positive correlation between internal control quality and corporate ESG information disclosure. Particularly, the internal control quality significantly affects corporate governance information disclosure. Moreover, the connection between internal control quality and enterprise ESG information disclosure is significantly and positively moderated by media attention. Specifically, negative media evaluations have significant impacts on enterprises. The main findings remain valid even after conducting multiple robustness tests, such as the lag test, propensity score matching, instrumental variable method, and alternative measurements for the key variables. This study widens the theoretical research frontier of internal and external supervision mechanisms.
Do socially responsible indices outperform conventional indices? Evidence from before and after the onset of Covid‐19
Authors: Jonwall Renu , Gupta Seema , Pahuja Shuchi
Published: May 2024

According to traditional portfolio theories constraints, restrictions, and screens applied in portfolio selection reduces the diversification opportunities which can impact financial performance. Is this true in the case of socially responsible investment (SRI)? To answer this, present study analyzes the performance of Socially Responsible (SR) indices in comparison to conventional indices in an emerging economy. The uniqueness of the study is that it analyses the performance of Shariah, ESG, and thematic indices in a single study. Further, the study measures the impact of Covid‐19 on them. Comparative performance evaluation was conducted by using absolute return analysis and risk‐adjusted measures namely, Sharpe ratio, Treynor ratio, tracking error, information ratio, capital asset pricing model (CAPM), Fama–French three‐factor, and Carhart's four‐factor models. The Structural break was identified, hence analysis was conducted for the total period (January 2017–March 2023) and two sub‐periods, that is, pre and post‐Covid‐19 period. No significant difference was found between the returns of SR indices and conventional indices as against the benchmark index on the basis of absolute return analysis. Sharpe ratio and Treynor ratio both were having negative values for all the SR and conventional indices. Tracking error for all the SR and Conventional indices were very low. The CAPM and both multi‐factor models univocally pointed toward the underperformance of all the SR (except S&P BSE 100 ESG index which had equal performance) and both conventional indices against the benchmark index. Noteworthy point is that only Shariah indices gave the highest returns during post‐Covid period. This research will help in deepening the SRI in the capital market. Companies should increase their ESG scores and make efforts to be listed on the SR indices. Policymakers should announce some kind of rebates, or recognition for star‐performing companies in the field of sustainability to encourage other companies to adopt SR practices in their business operations. The novelty of the current study is that it adds to the socially responsible literature by analyzing the performance of Shariah, ESG, and Thematic indices and conventional indices in a single study in the fastest‐growing economy of India and analyses the impact of Covid‐19 on this performance.
Visible‐Light Harvesting SrTiO3 Solid Solutions for Photocatalytic Hydrogen Evolution from Water
Authors: Xin Xueshang , Zou Hai , Du Shiwen , Bao Yunfeng , Zhang Fuxiang
Published: May 2024

The fabrication of solid solutions represents a compelling approach to modulating the physicochemical properties of materials. In this study, we achieved the successful synthesis of solid solutions comprising SrTiO3 and SrTaO2N (denoted as (SrTiO3)1‐x‐(SrTaO2N)x, 0≤x≤1) using the magnesium powder‐assisted nitridation method. The absorption edge of (SrTiO3)1‐x‐(SrTaO2N)x is tunable from 500 to 600 nm. The conduction band minimum (CBM) of (SrTiO3)1‐x‐(SrTaO2N)x comprises the Ti 3d orbitals and the Ta 5d orbitals, while the valence band maximum (VBM) consists of the O 2p and N 2p orbitals. The microstructure of the (SrTiO3)1‐x‐(SrTaO2N)x consists of small nanoparticles, exhibiting a larger specific surface area than the parent compounds of SrTiO3 and SrTaO2N. In the photocatalytic hydrogen evolution reaction (HER) with sacrificial reagents, the activity of solid solutions is notably superior to that of nitrogen‐doped SrTiO3 and SrTaO2N. This superiority is mainly attributed to its broad light absorption range and high charge separation efficiency, which indicates its potential as a promising photocatalytic material. Moreover, the magnesium powder‐assisted nitridation method exhibits obvious advantages for the synthesis of oxynitrides and bears instructional significance for the synthesis of other nitrogen‐containing compounds and even sulfur‐containing compounds.
Optimization of Electrochemical Reduction of Biomass Derived 5‐Hydroxymethylfurfural (HMF): A Volcano Plot and Bimetallic Catalysts
Authors: Luo Xingyu , Xie Cheng , Zhao Zhefei , Shi Meiqin , Zheng Huajun
Published: May 2024

2,5‐bis(hydroxymethyl)furan (BHMF) derived from 5‐Hydroxymethylfurfural (HMF) through a hydrogenation process has extensive applications in the production of resins, polymers, and artificial fibers. However, screening out the candidate and then modulating the active site to optimize the catalyst for high yield of BHMF are currently insufficient. In this study, Gibbs free energy diagrams of the reduction of HMF on 13 metals were presented, along with the identification of the rate‐determining step (RDS) with the highest reaction barrier for each metal. We attempted to construct a volcano plot for HMFRR reaction. Additionally, a strategy was proposed to adjust the reaction barriers of RDS by combining two appropriate metals. Further experiments confirmed that Pb with the lowest energy barrier exhibited the highest HMF conversion (BHMF selectivity) among single metals. The modified catalyst by doping Ag on Pb, further boosted the HMF conversion (BHMF selectivity) from 42.1 % (59.4 %) to 80.8 % (80.9 %), respectively. These results provide an approach to rationally design and construct the catalyst system for efficient conversion of HMF.
Cyclin‐dependent kinase 12 deficiency reprogrammes cellular metabolism to alleviate ferroptosis potential and promote the progression of castration‐resistant prostate cancer
Authors: Zhang Haozhe , Zhou Yi , Feng Yating , Hou Wenli , Chen Yafei , Xing Zengzhen , Zhang Yifan , Wei Qiang , Yin Yu , Guo Ju , Hu Hailiang
Published: May 2024

Background

Cyclin‐dependent kinase 12 (CDK12)‐deficient prostate cancer defines a subtype of castration‐resistant prostate cancer (CRPC) with a poor prognosis. Current therapy, including PARP inhibitors, shows minimal treatment efficacy for this subtype of CRPC, and the underlying mechanism remains elusive.

Methods

Based on bioinformatics analysis, we evaluated the relationship between CDK12 deficiency and prostate cancer patient's prognosis and treatment resistance. Furthermore, we used CRISPR‐Cas9 technology and mass spectrometry‐based metabolomic profiling to reveal the metabolic characteristics of CDK12‐deficient CRPC. To elucidate the specific mechanisms of CDK12 deficiency‐mediated CRPC metabolic reprogramming, we utilized cell RNA‐seq profiling and other molecular biology techniques, including cellular reactive oxygen species probes, mitochondrial function assays, ChIP‐qPCR and RNA stability analyses, to clarify the role of CDK12 in regulating mitochondrial function and its contribution to ferroptosis. Finally, through in vitro drug sensitivity testing and in vivo experiments in mice, we identified the therapeutic effects of the electron transport chain (ETC) inhibitor IACS‐010759 on CDK12‐deficient CRPC.

Results

CDK12‐deficient prostate cancers reprogramme cellular energy metabolism to support their aggressive progression. In particular, CDK12 deficiency enhanced the mitochondrial respiratory chain for electronic transfer and ATP synthesis to create a ferroptosis potential in CRPC cells. However, CDK12 deficiency downregulated ACSL4 expression, which counteracts the lipid oxidation stress, leading to the escape of CRPC cells from ferroptosis. Furthermore, targeting the ETC substantially inhibited the proliferation of CDK12‐deficient CRPC cells in vitro and in vivo, suggesting a potential new target for the therapy of CDK12‐deficient prostate cancer.

Conclusions

Our findings show that energy and lipid metabolism in CDK12‐deficient CRPC work together to drive CRPC progression and provide a metabolic insight into the worse prognosis of CDK12‐deficient prostate cancer patients.

Key points

CDK12 deficiency promotes castration‐resistant prostate cancer (CRPC) progression by reprogramming cellular metabolism.

CDK12 deficiency in CRPC leads to a more active mitochondrial electron transport chain (ETC), ensuring efficient cell energy supply.

CDK12 phosphorylates RNA Pol II to ensure the transcription of ACSL4 to regulate ferroptosis.

Mitochondrial ETC inhibitors exhibit better selectivity for CDK12‐deficient CRPC cells, offering a promising new therapeutic approach for this subtype of CRPC patients.
Efficacy and safety of pyrotinib combined with albumin‐bound paclitaxel as first‐line treatment for HER2‐positive metastatic breast cancer in patients previously treated with adjuvant and/or neoadjuvant trastuzumab therapy: The stage 1 results of a single‐arm, phase 2 prospective clinical trial
Authors: Man Xiaochu , Huang Jie , Sun Shujuan , Zhou Dongdong , Zhang Baoxuan , Fang Shu , Zheng Fangchao , Li Chao , Wang Xinzhao , Huang Wei , Wang Linlin , He Qingqing , Fu Hui , Zhang Yan , Liu Changrui , Dong Lin , Zhao Xianguang , Xu Liang , Sun Xiao , Fan Bingjie , Song Lihua , Zhou Zhengbo , Yu Jinming , Li Huihui
Published: May 2024

Objective

It has been observed that the prognosis of patients with HER2‐positive metastatic breast cancer has improved significantly with HER2‐targeted agents. However, there is still a lack of evidence regarding first‐line anti‐HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti‐HER2 treatment in these patients.

Methods

Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer were enrolled. Pyrotinib plus albumin‐bound paclitaxel were used as first‐line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically.

Results

From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow‐up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand‐foot syndrome (3.7%). Toll‐like receptor 3 (TLR3) and Proto‐oncogene tyrosine‐protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients.

Conclusions

This study demonstrates that pyrotinib plus albumin‐bound paclitaxel as a first‐line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2‐positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.
Role of tactile stimulation during the preweaning period on the development of the peripheral sensory sural (SU) nerve in adult artificially reared female rat
Authors: Melo Angel I. , Zempoalteca Rene , Ramirez‐Funez Gabriela , Anaya‐Hernández Arely , Porras Mercedes G. , Aguirre‐Benítez Elsa L. , González del Pliego Margarita , Armando Pérez‐Torres , Jiménez‐Estrada Ismael
Published: May 2024

Maternal deprivation, as a result of the artificial rearing (AR) paradigm, disturbs electrophysiological and histological characteristics of the peripheral sensory sural (SU) nerve of infant and adult male rats. Such changes are prevented by providing tactile or social stimulation during isolation. AR also affects the female rat's brain and behavior; however, it is unknown whether this early adverse experience also alters their SU nerve development or if tactile stimulation might prevent these possible developmental effects. To assess these possibilities, the electrophysiological and histological characteristics of the SU nerve from adult diestrus AR female rats that: (i) received no tactile stimulation (AR group), (ii) received tactile stimulation in the anogenital and body area (AR‐Tactile group), or (iii) were mother reared (MR group) were determined. We found that the amplitude, but not the area, of the evoked compound action potential response in SU nerves of AR rats was lower than those of SU nerves of MR female rats. Tactile stimulation prevented these effects.

Additionally, we found a reduction in the outer diameter and myelin thickness of axons, as well as a large proportion of axons with low myelin thickness in nerves of AR rats compared to the nerves of the MR and AR‐Tactile groups of rats; however, tactile stimulation only partially prevented these effects. Our data indicate that maternal deprivation disturbs the development of sensory SU nerves in female rats, whereas tactile stimulation partially prevents the changes generated by AR. Considering that our previous studies have shown more severe effects of AR on male SU nerve development, we suggest that sex‐associated factors may be involved in these processes.
A randomized controlled trial of a reading‐based weight bias intervention
Authors: Rosenbaum Diane L.
Published: May 2024

Objective

Weight bias, or negative attitudes about larger bodies, is a prevalent issue associated with problems in psychological and physical health, as well as discriminatory behaviors and weight stigma. Literature is mixed regarding the efficacy of weight bias reduction efforts. This study sought to combine three elements that yielded promising results from previous studies (i.e., reductions in beliefs about controllability of weight, reductions in stereotypical beliefs, and promotion of empathy) in a reading‐based intervention to reduce weight bias.

Methods

Participants (N = 319) were randomized to read a third‐person fictional narrative passage about a peer with obesity (intervention) or information on overweight and obesity (control).

Results

Linear mixed models controlling for body mass index and gender indicated the intervention was effective in producing reductions in overall weight bias and beliefs about controllability of weight from baseline to 1‐month follow‐up, but significant differences were not found in the domains of bias related to character disparagement or physical unattractiveness.

Discussion

This combination‐approach reading intervention is a promising strategy to reduce weight bias; however, future work is needed to more effectively target negative weight‐related attitudes pertaining to character and attractiveness.

Public Significance Statement

A reading‐based intervention targeting controllability of weight, stereotypes, and empathy can produce reductions in overall weight bias compared with a control condition. Reductions in beliefs about controllability of weight were shown from the reading‐based intervention. These findings may inform the development of programs to reduce negative attitudes about weight, which could help enhance quality of life and reduce risk for several mental health issues.
Identifying the generalizable controls on insect associations of native and non‐native trees
Authors: Gougherty Andrew V. , Klapwijk Maartje , Liebhold Andrew M. , Mech Angela , Trombik Jiří , Fei Songlin
Published: May 2024

Trees growing outside their native geographic ranges often exhibit exceptional growth and survival due in part to the lack of co‐evolved natural enemies that may limit their spread and suppress population growth. While most non‐native trees tend to accumulate natural enemies over time, it remains uncertain which host and insect characteristics affect these novel associations and whether novel associations follow patterns of assembly similar to those of native hosts. Here, we used a dataset of insect–host tree associations in Europe to model which native insect species are paired with which native tree species, and then tested the model on its ability to predict which native insects are paired with which non‐native trees. We show that native and non‐native tree species closely related to known hosts are more likely to be hosts themselves, but that native host geographic range size, insect feeding guild, and sampling effort similarly affect insect associations. Our model had a strong ability to predict which insect species utilize non‐native trees as hosts, but evolutionarily isolated tree species posed the greatest challenge to the model. These results demonstrate that insect–host associations can be reliably predicted, regardless of whether insect and host trees have co‐evolved, and provide a framework for predicting future pest threats using a select number of easily attainable tree and insect characteristics.