bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymmetric Fluorination Methods: Application in the Stereoselective Synthesis of Fluorinated Drugs
Authors: Bizet Vincent , Cahard Dominique
Published: August 2023

This chapter is dedicated to stereoselective aspects of synthesis of biologically active fluorinated compounds. The construction of nonracemic stereogenic carbon–fluorine centers could be achieved through electrophilic or nucleophilic fluorination eitherviadiastereo‐ or enantioselective approaches. Application of asymmetric fluorination for stereoselective synthesis of drugs and potential drugs is covered.
Chromosomal Aberrations in Cancer
Authors: Vander Weele David J. , McNerney Megan E. , Le Beau Michelle M.
Published: August 2023

Overview

The malignant cells of most patients who have leukemia, lymphoma, or a solid tumor have acquired clonal chromosomal abnormalities, the identification of which can aid in establishing the correct diagnosis and prognosis and in the selection of therapy. Today, our arsenal of approaches to characterize an individual's malignant disease combines pathologic evaluation, cytogenetic analysis, and molecular studies, typically focused on a few key genes. The advent of high‐throughput methods, such as next‐generation sequencing, capable of surveying the entire genome or large panels of cancer‐related genes, presents new options for a revolutionary change in the way we diagnose, characterize, and treat cancer. The vision for the future entails an integrated molecular profile, that is, chromosomal pattern, gene/miRNA expression, DNA methylation/epigenomic pattern, gene mutation status, and chemosensitivity of each patient's tumor, as well as predisposition to disease, facilitating the development of an individualized treatment plan with decreased toxicities and prolonged survival.
Herpesviruses
Authors: Cohen Jeffrey I.
Published: August 2023

Overview

Eight herpesviruses have been isolated from humans: two of these, Epstein–Barr virus (EBV) and Kaposi sarcoma‐associated herpesvirus (KSHV), are associated with human tumors. EBV has been detected in lesions from patients with post‐transplant lymphoproliferative disease, nasopharyngeal and some types of gastric carcinoma, Burkitt lymphoma, Hodgkin lymphoma, and certain other lymphoid tumors. KSHV is associated with Kaposi sarcoma, primary effusion lymphoma, and Castleman disease. Each of these viruses encodes proteins important for establishment of latency, transforming cells, and evading the immune system.
Principles of Radiation Oncology
Authors: Connell Philip P. , Weichselbaum Ralph R.
Published: August 2023

Overview

In recent decades, we have witnessed major technologic advances that have influenced how radiotherapy is delivered to cancer patients. Simultaneously, our understanding of the underlying basic biology that governs radiation effects in human cells and tissues has grown rapidly. Here, we summarize some of these key advances and place them into the context of the evolving paradigms that shape cancer therapeutics more generally. Key biologic topics covered in this chapter involve the molecular responses of cells to DNA damage by ionizing radiation, including the repair of DNA damage, cell cycle arrest and death, cellular signaling, and the influence of tumor‐initiating cells (tumor stem cells) on post‐treatment outcomes. As radiation generates an inflammatory microenvironment in tumors, drugs that modulate immune functions also represent a potential therapeutic opportunity. We also describe newer biology‐based technologies that can accurately predict the intrinsic sensitivity of cells to radiation, and pharmacologic agents that can modulate this radiation sensitivity. Finally, this chapter reviews the major physics‐based technologic innovations that have improved the accuracy and utility of clinical radiotherapy. Despite these advances, several unmet challenges continue to limit the impact of radiotherapy, and these remaining hurdles should be the factors that guide future innovations of our field.
Folate Antagonists
Authors: Cole Peter D. , Figueiredo Lisa , Bertino Joseph R.
Published: August 2023

Overview

Folic acid antagonists (antifols) are cytotoxic drugs used as antineoplastic, antimicrobial, anti‐inflammatory, and immune‐suppressive agents. While several folate antagonists have been developed, methotrexate (4‐amino‐4‐deoxy‐10‐N‐methyl‐pteroylglutamic acid; MTX) is the antifol with the most extensive history and widest spectrum of use.MTXremains an essential drug in curative chemotherapy regimens used to treat patients with acute lymphoblastic leukemia, osteosarcoma, and choriocarcinoma and is an important agent in the therapy of patients with lymphoma, breast cancer, bladder cancer, and head and neck cancer. In addition, it is used for patients with nonmalignant diseases such as rheumatoid arthritis, psoriasis, autoimmune diseases, and graft versus host disease. This chapter will review the clinical use of and the metabolism ofMTXand discuss structurally related folate antagonists that have been developed to overcome resistance or have alternate intracellular targets.
Malignant Melanoma
Authors: Ko Justin M. , Swetter Susan M. , Zager Jonathan S. , Sondak Vernon K. , Woodman Scott E. , Margolin Kim A.
Published: August 2023

Overview

Melanoma comprises a wide variety of malignant cell types arising from the skin, the mucous membranes, and the pigmented cells of the eye. While these tumors are all classified as melanoma and share a common molecular biology of pigmentation and biological resemblance to cells of neural crest origin, important distinctions in other molecular characteristics and patterns of exposure to ultraviolet light as a carcinogen determine their clinical natural history, including the response to therapeutic interventions. While the majority of melanomas are diagnosed at an early stage and curable with minimal surgery, melanoma has the potential for early and widespread dissemination via lymphatic and hematogenous routes. Surgery remains the mainstay of therapy for primary, regional, and many cases of single‐ or oligo‐metastatic disease, but systemic therapies have dramatically improved the prognosis for metastatic melanoma, particularly immunotherapies that enhance existing cellular immunity. The rapid discovery of new molecular targets, immunotherapy combinations (including the use of radiotherapy), and understanding of the mechanisms of therapeutic resistance are likely to lead to even greater improvements in the prognosis for patients with melanoma in the near future.
The Myelodysplastic Syndrome
Authors: Silverman Lewis R.
Published: August 2023

Overview

The existence of a hematopoietic disorder characterized by anemia and dyspoiesis preceding the onset of acute myelocytic leukemia (AML) has been recognized since the early part of the twentieth century. Initially designated as preleukemia, the syndrome was ill defined and could only be established with certainty retrospectively. Moreover, the terminology itself conveyed an unwarranted confidence in predicting the outcome that often belied the facts. The more accurately descriptive and appropriate designation as a myelodysplastic syndrome (MDS) was adopted in 1976 by the French–American–British (FAB) study group. The FAB classification permitted the prospective identification of patients within this heterogeneous clonal disorder.

MDS, derived from a multipotent hematopoietic stem cell, is characterized clinically by a hyperproliferative bone marrow, reflective of ineffective hematopoiesis, and is accompanied by one or more peripheral blood cytopenias. Bone marrow failure results, leading to death from bleeding and infection in the majority, while transformation to acute leukemia occurs in up to 40% of patients. The evolution of the disease proceeds in accordance with the multistep pathogenesis theory of carcinogenesis and can thus serve as an important model in furthering our understanding of the processes involved in neoplastic transformation.

This constellation of findings raises the question of whether MDS represents a frank neoplastic state or is merely a preneoplastic condition in transition. The syndrome appears to represent a spectrum where the initial lesion in the genome, though clinically undetectable, subsequently evolves, with the acquisition of additional genetic and epigenetic lesions, to a state of frank neoplasia.

The designation of this disorder as an MDS, rather than preleukemia, permits its distinction from other abnormalities that are known to be associated with the development of acute leukemia. These latter include the classic myeloproliferative syndromes (polycythemia vera, chronic myelocytic leukemia, agnogenic myeloid metaplasia, essential thrombocythemia), aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH), as well as Fanconi, Bloom, and Down syndromes. These particular “preleukemic states” are beyond the scope of this chapter.

MDS can be further divided into primary and secondary syndromes. The former arise de novo and are of indeterminate etiology, while the latter are induced by identifiable environmental, occupational, or iatrogenic causes.

Estimates of the incidence of MDS range from a frequency equal to that of AML or approximately 14,000 new cases per year in the United States to almost twice that of AML. The SEER database now tracks the disease; thus more accurate data will be available in the future. An estimate based on medical insurance claims indicated a total of 107,000 cases in the observation period from 2009 through 2011. The consensus is that the incidence is increasing owing to a number of factors, including greater awareness, greater diagnostic precision, and the aging of the population.
Acute Myeloid Leukemia in Adults: Mast Cell Leukemia and Other Mast Cell Neoplasms
Authors: Stone Richard M. , Schiffer Charles A.
Published: August 2023

Overview

Acute myeloid leukemia (AML) is the most common variant of acute leukemia occurring in adults, comprising approximately 80% of acute leukemia cases diagnosed in individuals of age >20 years. Remarkable advances in transfusion medicine, treatment of infections, development of potent antiemetics, improved chemotherapeutic approaches, and increased use of safer allogeneic transplantation have led to an improved outcome at least in younger patients. Moreover, a more sophisticated understanding of pathophysiology, particularly in the area of genomics, may soon lead to less toxic, patient‐specific, and more effective therapies. At present, approximately 80% of younger (age <60 years) adults and 30%–50% of all older patients achieve complete remission (CR) defined as a morphologically normal bone marrow with reasonable neutrophil and platelet counts and no evidence of extramedullary disease. Varying with patient age and other biologic factors, 10–70% of these complete responders can be expected to achieve long‐term survival with the likelihood that most of these individuals are cured of their disease. However, AML is largely an intrinsically chemoresistant disease, the outcome in older adults has changed little, and the chemotherapeutic approach has remained stagnant.
Acute Lymphoblastic Leukemia
Authors: Jain Nitin , Faderl Stefan , Kantarjian Hagop M. , O'Brien Susan
Published: August 2023

Overview

In adults, acute lymphoblastic leukemia (ALL) is a disease with poor prognosis. In the last several years, there have been significant advances in understanding the disease biology, prognostication, and in the development of novel therapies. These include development of monoclonal antibodies, antibody–drug conjugates, tyrosine kinase inhibitors, and more recently, chimeric antigen receptor T‐cell therapy. These therapies are beginning to result in improvements in survival of patients with ALL.
Non‐Hodgkin's Lymphoma
Authors: Freedman Arnold S. , LaCasce Ann S.
Published: August 2023

Overview

The malignant lymphomas are neoplastic transformations of cells that reside predominantly within lymphoid tissues. Although Hodgkin lymphomas (HLs) and non‐Hodgkin lymphomas (NHLs) infiltrate lymphohematopoietic tissues, their biologic and clinical behaviors are distinct. They differ with neoplastic cells of origin, sites of disease, presence of specific symptoms, and response to treatment. Although both are among the most sensitive malignancies to radiation and cytotoxic therapy, their cure rates markedly differ. HLs are cured in nearly 80% of all patients employing both conventional and salvage treatment strategies whereas NHLs are cured in fewer than 50% of patients.
Endocrine Complications and Paraneoplastic Syndromes
Authors: Yeung Sai‐Ching Jim , Gagel Robert F.
Published: August 2023

Overview

Transformation of normal cells results in activation and/or suppression of a number of hormonally active genes. This chapter outlines the several clinical endocrine paraneoplastic syndromes and their appropriate management. Treatment of cancer results in a number of endocrine or metabolic manifestations, most of which are related to hormone deficiency or drug‐related toxicity. The introduction of targeted therapy that disrupts signaling pathways and immunotherapy, contrary to expectations, has actually increased the number of endocrine manifestations. This chapter will chronicle the major new endocrine toxicities in addition to those observed with older cytotoxic chemotherapies and radiation.
Infections in Patients with Cancer
Authors: Nesher Lior , Rolston Kenneth V. I.
Published: August 2023

Overview

Patients with cancer have an increased risk of developing infections, owing both to their underlying disease and its treatment. This risk appears to be greatest in patients with hematologic malignancies and in hematopoietic cell transplant recipients. This is due primarily to the development of various immunologic defects such as neutropenia and impaired cellular and/or humoral immunity, each associated with a unique spectrum of infection. Newer therapeutic modalities for the treatment of some cancers are changing the spectrum of infections as are the increasing use of catheters and other medical devices. While bacterial infections are documented most often, opportunistic fungal and viral infections are being encountered with increasing frequency. The morbidity and mortality of infections in cancer patients is generally greater than in the general population. Thus, early diagnosis and the prompt administration of appropriate therapy are of paramount importance. Antimicrobial resistance among these pathogens has become a worldwide problem, which can only be partially tackled by the development of novel agents. Consequently, the importance of conducting frequent epidemiologic surveillance in order to detect local epidemiologic shifts and of infection prevention, infection control, and antimicrobial stewardship cannot be emphasized enough. The number of cancer survivors is steadily increasing. Many of these patients remain immunosuppressed for substantial periods of time. Keeping these survivors healthy and infection free will continue to be a challenge for years to come.
Development of programs to predict the occurrence of mucositis from digital imaging and communications in medicine data by machine learning in head and neck volumetric modulated radiotherapy
Authors: Rachi Toshiya , Ariji Takaki , Takahashi Shinichi
Published: August 2023

Volumetric modulated arc therapy (VMAT) with cisplatin for head and neck cancer is often accompanied by symptoms of pharyngeal and oral mucositis. However, no standard medical program exists for the prevention and treatment of mucositis, and the mechanisms of mucositis have not yet been fully proven. Therefore, adaptive radiotherapy (ART), which is a re‐planning process, is administered when severe mucositis develops during the treatment period. We extracted the treatment plans of patients who developed severe mucositis from DICOM data and used machine learning to determine its quantitative features. This study aimed to develop a machine learning program that can predict the development of mucositis requiring ART. This study included 61 patients who received concurrent chemotherapy and radiotherapy (RT). For each patient, the equivalent square field size of each segmental irradiation field used for VMAT, dose per segment (Gy), clinical target volume high, and mean dose of the oral cavity (Gy) were calculated. Furthermore, 671 five‐dimensional lists were generated from the acquired data. Support vector machine (SVM) and K‐nearest neighbor (KNN) were used for machine learning. For the accuracy score, the test size was varied from 10% to 90%, and the random number of data extracted in each test size was further varied from 1 to 100 to calculate a mean accuracy score. The mean accuracy scores of SVM and KNN were 0.981 ± 0.020 and 0.972 ± 0.033, respectively. The presence or absence of ART for mucositis was classified with high accuracy. The classification of the five‐dimensional list was implemented with high accuracy, and a program was constructed to predict the onset of mucositis requiring ART before treatment began. This study suggests that it may support preventive measures against mucositis and the completion of RT without having to re‐plan.
New SAMHSA strategic plan focuses on opioids and suicides
Authors: Knopf Alison
Published: August 2023

The 2023–2026 Strategic Plan for the Substance Abuse and Mental Health Services Administration (SAMHSA) focuses on two main missions: reducing opioid overdoses and reducing suicides. There is a stress on mental health, especially among the workforce, and a general reference to “behavioral” health care, which of course includes both mental health and addiction.
Two‐Dimensional Semiconductors: From Device Processing to Circuit Integration
Authors: Sheng Chuming , Dong Xiangqi , Zhu Yuxuan , Wang Xinyu , Chen Xinyu , Xia Yin , Xu Zihan , Zhou Peng , Wan Jing , Bao Wenzhong
Published: August 2023

The atomically thin nature and exceptional electrical properties of 2D materials (2DMs) have garnered significant interest in circuit applications. Researchers have developed circuits based on wafer‐level 2DM fabrication and monolithic integration in the laboratory. Numerous studies have been conducted on discrete device processes; however, circuit manufacturing is a multifaceted and methodical engineering process that demands seamless integration of multiple procedures. Notably, the optimization of crucial processes holds paramount significance in achieving expected results. This review presents the existing research on process integration of 2DM devices and circuit applications. The selection of suitable 2DMs for circuit applications is outlined, considering their excellent theoretical properties and feasible high‐quality growth processes. Drawing on highly mature semiconductor manufacturing process, while incorporating customized key processes, 2DM devices have the potential to strongly compete with, and even outperform, the conventional devices. Finally, the recent circuit applications of 2DMs are also discussed in detail. 2DM integrated circuits (2DM ICs) are now being practically applied in advanced manufacturing, transitioning from laboratory development to fabrication plant deployment. The implementation of underlying 2DM IC fabrication provides effective and unique solutions for More Moore, More than Moore, and Beyond CMOS technology routes.
Li2MnO3: A Catalyst for a Liquid Cl2 Electrode in Low‐Temperature Aqueous Batteries
Authors: Sui Yiming , Zhuo Zengqing , Lei Ming , Wang Lu , Yu Mingliang , Scida Alexis M. , Sandstrom Sean K. , Stickle William , O'Larey Timothy D. , Jiang De‐e , Yang Wanli , Ji Xiulei
Published: August 2023

Li2MnO3 has been contemplated as a high‐capacity cathode candidate for Li‐ion batteries; however, it evolves oxygen during battery charging under ambient conditions, which hinders a reversible reaction. However, it is unclear if this irreversible process still holds under subambient conditions. Here, the low‐temperature electrochemical properties of Li2MnO3 in an aqueous LiCl electrolyte are evaluated and a reversible discharge capacity of 302 mAh g−1 at a potential of 1.0 V versus Ag/AgCl at −78 °C with good rate capability and stable cycling performance, in sharp contrast to the findings in a typical Li2MnO3 cell cycled at room temperature, is observed. However, the results reveal that the capacity does not originate from the reversible oxygen oxidation in Li2MnO3 but the reversible Cl2(l)/Cl−(aq.) redox from the electrolyte. The results demonstrate the good catalytic properties of Li2MnO3 to promote the Cl2/Cl− redox at low temperatures.
Apoptosis of Multi‐Drug ResistantCandidaSpecies on Microstructured Titanium Surfaces
Authors: Le Phuc H. , Linklater Denver P. , Aburto‐Medina Arturo , Nie Shuai , Williamson Nicholas A. , Crawford Russell J. , Maclaughlin Shane , Ivanova Elena P.
Published: August 2023

The proportion of hospital‐acquired medical device infections caused by pathogenic, multi‐drug resistantCandidaspecies occurs in up to 10% of implantations. In this study, a unique antifungal micro‐pillared titanium surface pattern is developed, which demonstrates both fungicidal and fungistatic activity, persistently deterring biofilm formation byCandida albicansand multi‐drug resistantCandida aurisfungi for up to 7 days. The Ti micropillars of 3.5 µm height are fabricated using maskless inductively coupled plasma reactive ion etching. The micro‐textured surface consistently kills ≈50% ofCandidaspp. irreversibly attached cells and prevent the proliferation of the remaining cells by inducing programmed cell death. Proteomic analysis reveals thatCandidacells undergo extensive metabolic stress, preventing the transformation from yeast to the filamentous/hyphal cell phenotype that is essential for establishing a typical in vitro biofilm. The mechanical stress imparted following interaction with the micropillars injures attaching cells and induces apoptosis whereby theCandidacells are unable to be revived in a non‐stress environment. These findings shed new insight toward the design of durable antifungal surfaces that prevent biofilm formation by pathogenic, multi‐drug resistant yeasts.
A Spot Ionogel for Visual Early‐Warning of Illegal Lead Concentrations Coupling Inorganic Perovskite Crystallization and Photoluminescence
Authors: Fu Jie , Zhang Lei , Liu Jia‐Ying , Zhang Guo‐Hao , Wang Shuang‐Long , Zhu Qiu‐Hong , Qin Song , He Ling , Tao Guo‐Hong
Published: August 2023

Lead halide perovskite solar cells still have potential lead leakage under the influence of natural forces, which has attracted widespread attention. In future large‐scale applications, it is necessary to monitor and control the concentration of lead in the environment according to local laws and regulations. In this work, the coupling strategy of inorganic perovskite crystallization and photoluminescence is proposed for the first time to achieve the detection of lead in the environment. An easy‐to‐use, low‐cost, and portable PVA/C6mimBr/CsBr ionogel (PCCI) device is prepared through solution process for on‐site detection of Pb(II). The limit detection of PCCI is 236 mg kg−1, which is close to and lower than the statutory standard of 250 mg kg−1 in China's agricultural regulations, and is expected to achieve on‐site early‐warning. This work may promote the development of environmental early‐warning devices in line with laws and regulations.
Multi‐Type Topological States in Higher‐Order Photonic Insulators Based on Kagome Metal Lattices
Authors: Tao Liyun , Liu Yahong , Zhou Xin , Du Lianlian , Li Meize , Ji Ruonan , Song Kun , Zhao Xiaopeng
Published: August 2023

Tunability of topological photonic structures opens a new avenue for photonics research. The rich physical characteristics of the topological photonics have great significance in practical implementations. In this paper, multi‐type topological states are demonstrated in higher‐order photonic topological insulators based on Kagome metal lattices. By stretching or rotating Kagome metal lattices, two types of topological insulators are obtained, and multi‐type topological states are observed. By stretching Kagome metal lattices, a 1D topological edge state and two types of higher‐order topological corner states (corresponding to a traditional higher‐order topological corner state based on nearest‐neighbor coupling and a new higher‐order corner state caused by long‐range interactions) are obtained in a classical quantization of dipole moments higher‐order topological insulators. By rotating Kagome metal lattices, dual‐band higher‐order valley‐Hall topological insulators are achieved with nodal ring degeneracy. Odd‐type and even‐type topological states are obtained. Achieving reconfigurable, multi‐type, and multi‐band topological insulators by using a single structural unit provides interesting insights into topological photonics and provides an unconventional approach to explore photonic systems and condensed matter physics.
3D Sponge Electrodes for Soft Wearable Bioelectronics
Authors: Lin Fenge , Cheng Wenlong
Published: August 2023

By definition, a sponge refers to a soft and porous material, which is typically made from cellulose or synthetic polymers. Structurally, it is 3D offering a high surface‐to‐volume ratio; mechanically, it is elastic and durable; economically, it is inexpensive and can be produced at industrial scales. These attributes promote a strong research interest in exploring 3D sponges for applications in absorption, separation, catalysis, and electronics. This work is dedicated to the discussion of the recent progress in design of mechanically deformable sponge electrodes for their application in soft electronics. First, the characteristics and advantages of sponge electrodes are described, which is followed by the discussion of various active materials for fabricating 3D sponge electrodes, including carbon, metal, conductive polymers, MXenes, and their hybrids. Then, the viable fabrication methodologies are reviewed by comparing their advantages and disadvantages. Furthermore, the applications of 3D conductive sponges in stretchable conductors, sensors, energy storage devices, and integrated systems are discussed. Finally, the challenges and opportunities in future sponge‐based soft electronics are covered.
Multidentate Chelation Enables High‐Efficiency Mn2+ Storage in Polyimide Covalent Organic Framework for Aqueous All Mn‐Ion Battery
Authors: Cai Lejuan , Lu Lisha , Lan Yingying , Zhang Youming , Wang Jianlin , Lin Zijia , Li Renjie , Zhang Fan , Yu Jie , Lu Wengang , Bai Xuedong , Wang Wenlong
Published: August 2023

Aqueous divalent manganese ions (Mn2+) have recently emerged as a promising candidate for the development of multivalent ion rechargeable batteries. Here, a multidentate chelation strategy is demonstrated for high‐efficiency Mn2+ storage in a polyimide covalent organic framework (PI‐COF) anode based on the understanding of Mn2+ coordination chemistry. In contrast to other multivalent cations, Mn2+ can bond with two adjacent enolized carbonyl groups and the triazine ring to form a novel multidentate chelation configuration in charged PI‐COF lattice. As such, a large Mn2+ storage capacity of 120 mAh g−1 at 0.2 A g−1 along with great cycling stability can be achieved in PI‐COF. Ex situ characterization and first‐principles calculations further identify the occurrence of polydentate Mn2+ coordination and its critical role in stabilizing the enolized PI‐COF intermediates. Notably, an all Mn‐ion prototype cell assembly is demonstrated by coupling a PI‐COF/Mn2+ anode with a high‐voltage cathode based on MnO2/Mn2+ conversion reaction. The well‐designed cell exhibits a stable discharge plateau of 1.28 V and an impressive capacity of 115 mAh g−1 at the current density of 0.2 A g−1. This work highlights the utility of coordination chemistry for achieving highly efficient energy storage by optimizing the matching between energy‐carrying ions and organic host materials.
A High‐Capacity Gradient Zn Powder Anode for Flexible Zn‐Ion Batteries
Authors: Zhao Xin , Gao Yong , Cao Qinghe , Bu Fan , Pu Jie , Wang Yuxuan , Guan Cao
Published: August 2023

Zn powder‐based anodes are promising for flexible Zn‐ion batteries with large‐scale production, but the drawbacks such as dendrite growth and side reactions strictly hinder their wide application. Herein, a free‐standing Zn powder‐based anode with gradient particle size and porosity is facilely constructed for flexible Zn‐ion batteries. The gradient design not only optimizes the electric field distribution and the Zn‐ion flux but also induces ideal bottom‐up deposition and top‐down stripping behaviors of Zn, thus suppressing dendrite growth. As a result, the flexible gradient Zn powder anode can be stably cycled for 1250 h at 1 mA cm−2/1 mAh cm−2, and even at high current/capacity of 5 mA cm−2/5 mAh cm−2, it still achieves a long lifespan of 130 h, which outperforms its non‐gradient counterparts and most previous results from Zn powder‐based anodes. The gradient strategy is expected to inspire the extensive utilization of Zn powder‐based anodes for flexible energy storage devices.
Rational Design of Benzo‐Crown Ether Electrolyte Additives for High‐Performance Li‐O2 Batteries
Authors: Zhang Qi , Li Yuke , Poh Eng Tuan , Xing Zhenxiang , Zhang Mingsheng , Wang Meng , Sun Zejun , Pan Jisheng , Vummaleti Sai Vikrama Chaitanya , Zhang Jia , Chen Wei
Published: August 2023

Despite theoretical predictions of exceptional gravimetric energy densities in Li‐O2 batteries (LOBs), the current research forefront faces challenges, including high charge overpotential, cathode clogging, parasitic reactions, and Li anode corrosion. Herein, benzo‐crown ethers (BCEs) with varying cavity sizes are used as electrolyte additives to exploit their strong binding toward Li+ and promote the solution growth of Li2O2 with reduced particle size. Notably, the cell with benzo‐18‐crown‐6 ether (B18C6) enables the largest discharge capacity of 14948 mAh g−1. Upon charging, these additives accelerate Li2O2 oxidation through the strong binding with Li+ and the extended electrolyte/Li2O2 interface, resulting in improved reversibility, reduced charge overpotential, and prolonged cycle life. Besides, these additives also stabilize the Li anode by regulating Li+ migration and electron exchange, reducing dendritic growth and anode corrosion. This work presents insights into the rational design of BCEs as additives for high‐performance LOBs.
Effects of racism and discrimination on mental health among young people in Victoria, Australia, during COVID‐19 lockdown
Authors: Doery Kate , Guo Shuaijun , Jones Roxanne , O'Connor Meredith , Olsson Craig A. , Harriott Linette , Guerra Carmel , Priest Naomi
Published: August 2023

Racism and discrimination are fundamental determinants of health inequities, with young people particularly vulnerable. Since the onset of the global COVID‐19 pandemic in 2020, reports of racism and discrimination rose sharply. This study examined direct discrimination, vicarious racial discrimination, heightened vigilance, worries about experiencing racial discrimination, COVID‐19‐related stressors and their associations with young people's mental health during COVID‐19 lockdown in 2020. A community‐based, cross‐sectional online survey collected data from 363 young people aged 16–24 years living in Victoria, Australia, of whom 45.3% self‐identified as being from a multicultural background and 3.7% as Aboriginal and/or Torres Strait Islander. 73.7% reported direct discrimination, 88.9% reported vicarious racial discrimination, 84.3% reported heightened vigilance, and 62.8% reported worries about experiencing racial discrimination. Half (51.3%) of the participants experienced one or two COVID‐19‐related stressors. 53.1% of participants reported moderate‐to‐high levels of distress or negative mood state. Experiences of direct discrimination, vicarious racial discrimination, heightened vigilance, worries about experiencing racial discrimination and multiple COVID‐19‐related stressors (3+) were associated with negative mood state, after adjusting for ethnicity, age, gender and socioeconomic position. Addressing racism and discrimination is critical to addressing health inequities for young people.
Plethysmograph training: A refinement for collection of respiration data in mice
Authors: Sørli Jorid B. , Hougaard Karin S. , Hadrup Niels
Published: August 2023

Inhaled chemicals can harm the airways. Different effects can result in distinct changes in respiratory patterns; the type of change indicates where and how the respiratory system is affected. Furthermore, changes in respiratory patterns may be detected at much lower substance concentrations than those that cause more serious effects, such as histopathological changes. Changes in respiratory patterns can be studied experimentally by monitoring the breathing of mice placed in plethysmographs and exposing head‐out to the test substance. The method is well established; however, it is not known if training mice in being restrained in the plethysmograph could increase the quality of data collection. Here we report the results of training mice to be restrained in plethysmographs for 5 consecutive days, with respect to body weight, respiratory parameters, and time spent in the plethysmograph, before they are removed because of unstable breathing patterns. The mice tolerated the procedure better (measured by time in the plethysmograph) on the second day of training than the first day. Training did not change the breathing parameters between days. Breathing parameters stabilized within 5 min after the mice were placed in the plethysmographs on all days. There was an average of 3% weight loss between the first and last days of the training, indicating that the training procedure placed some strain on the animals. Training reduces the number of mice attempting to escape from the plethysmograph.
Copper(I)‐Catalyzed Asymmetric Hydrophosphination of 3,3‐Disubstituted Cyclopropenes
Authors: Zhang Shuai , Jiang Nan , Xiao Jun‐Zhao , Lin Guo‐Qiang , Yin Liang
Published: August 2023

Herein, a copper(I)‐catalyzed asymmetric hydrophosphination of 3,3‐disubstituted cyclopropenes is reported. It provides a series of phosphine derivatives in high to excellent diastereo‐ and enantioselectivities. The methodology enjoys broad substrate scope on both 3,3‐disubstituted cyclopropenes and diarylphosphines. The high stereoselectivity is attributed to both the high stability of the Cu(I)‐(R,R)‐QUINOXP* complex in the presence of stoichiometric HPPh2 and the produced phosphines, and the high‐performance asymmetric induction of the Cu(I)‐(R,R)‐QUINOXP* complex. Finally, the method is used for the synthesis of new chiral phosphine‐olefin compounds built on a cyclopropane skeleton, one of which serves as a wonderful ligand in Rh‐catalyzed asymmetric conjugate addition of phenylboronic acid to various α,β‐unsaturated compounds.
Die Strukturaufklärung des ersten sex‐induzierenden Pheromons einer Kieselalge
Authors: A. Klapper Franziska , Kiel Christine , Bellstedt Peter , Vyverman Wim , Pohnert Georg
Published: August 2023

Kieselalgen sind weit verbreitete einzellige Mikroalgen, die für ≈20 % der globalen photosynthetischen CO2 Fixierung verantwortlich sind. Unser Wissen über die fundamentalen Aspekte ihrer Biologie, zu denen auch die sexuelle Fortpflanzung gehört, ist jedoch begrenzt. Für eine erfolgreiche Paarung der Einzeller ist die chemische, Pheromonvermittelte Kommunikation von höchster Wichtigkeit. Mit Hilfe von Pheromonen kann die sexuelle Aktivität synchronisiert und der Prozess der Partnerfindung mediiert werden. In der Diatomee Seminavis robusta wurde bereits der Lockstoff, der die Suchbewegung zum Partner vermittelt, identifiziert. Die Strukturen weiterer Metaboliten, welche die Zellen sexuell synchronisieren blieben allerdings unbekannt. Diese sex‐induzierenden Pheromone (SIP) lösen eine Zellzyklusarretierung aus und induzieren zusätzlich die Freisetzung des richtungsweisenden Lockstoffs. Im Folgenden beschreiben wir die anspruchsvolle Strukturaufklärung eines SIPs von S. robusta. Dafür wurde ein potentieller aktiver Metabolit in einer Metabolomstudie identifiziert und durch Isotopenmarkierungsexperimente, NMR, Elektrospray MSn Analysen und chemische Umsetzungen aufgeklärt. Die Verwendung der Massenspektrometrie im negativen Ionenmodus war von essentieller Bedeutung bei der Entschlüsselung des zyklischen Heptapeptids, welches Hydroxyprolin‐ und ein neuartiges β‐sulfatiertes Aspartat enthält. Das SIP ist bereits in femtomolaren Konzentrationen wirksam.
Electrochemical Nanoreactor Provides a Comprehensive View of Isocitrate Dehydrogenase Cancer‐drug Kinetics
Authors: Herold Ryan A. , Schofield Christopher J. , Armstrong Fraser A.
Published: August 2023

The ability to control enzyme cascades entrapped in a nanoporous electrode material (the “Electrochemical Leaf”, e‐Leaf) has been exploited to gain detailed kinetic insight into the mechanism of an anti‐cancer drug. Ivosidenib, used to treat acute myeloid leukemia, acts on a common cancer‐linked variant of isocitrate dehydrogenase 1 (IDH1 R132H) inhibiting its “gain‐of‐function” activity—the undesired reduction of 2‐oxoglutarate (2OG) to the oncometabolite 2‐hydroxyglutarate (2HG). The e‐Leaf quantifies the kinetics of IDH1 R132H inhibition across a wide and continuous range of conditions, efficiently revealing factors underlying the inhibitor residence time. Selective inhibition of IDH1 R132H by Ivosidenib and another inhibitor, Novartis 224, is readily resolved as a two‐stage process whereby initial rapid non‐inhibitory binding is followed by a slower step to give the inhibitory complex. These kinetic features are likely present in other allosteric inhibitors of IDH1/2. Such details, essential for understanding inhibition mechanisms, are not readily resolved in conventional steady‐state kinetics or by techniques that rely only on measuring binding. Extending the new method and analytical framework presented here to other enzyme systems will be straightforward and should rapidly reveal insight that is difficult or often impossible to obtain using other methods.
Central composite design‐based response surface methodology for optimization of tetrodotoxin extraction from the horseshoe crab Carcinoscorpius rotundicauda
Authors: Tran Dang Thuan , Dinh Cuc T. , Dang Mai T. , Do Cam Van T. , Le Ho Khanh Hy , Le Truong Giang , Dao Viet Ha
Published: August 2023

Tetrodotoxin analogues (TTXs) used in research and development were originated from biological sources for the last decades. Among TTXs‐bearing aquatic animals, horseshoe crab Carcinoscorpius rotundicauda from Vietnam's Coast was reported to contain a high level of TTXs, indicating a promising source for extraction and purification of TTXs. In this work, horseshoe crab C. rotundicauda collected from Can Gio Coast, Vietnam was used for TTX extraction using homogenization‐assisted method with acetic acid solvent. The extraction process was analysed and optimized by single‐factor investigation and response surface methodology (RSM). Single‐factor investigation pointed out that the optimal conditions for TTX recovery yield from C. rotundicauda's soft tissues were homogenization time of 20 min, acetic acid concentration of 1.0%, solvent/matrix ratio of 4 mL/g, extraction temperature of 70°C, extraction time of 30 min and number of extraction of two times. The most significant factors including acetic acid concentration, solvent/matrix ratio and extraction temperature were utilized for constructing the RSM model to predict TTX recovery yield. The maximal TTX recovery yield predicted from RSM model was 97.3% under solvent/matrix ratio of 4 mL/g, extraction temperature of 70°C and acetic acid concentration of 1% (v/v). The RSM model displayed a high stability and precision for prediction of TTX recovery yield from experiments of 1–10 kg C. rotundicauda's soft tissues/batch extractions producing low errors (−1.95% to 1.85%). TTXs in C. rotundicauda's soft tissues were elucidated by HPLC‐MS/MS, revealing the presence of three analogues TTX, 4epi‐TTX and Anh‐TTX with their contents of 43.02, 22.54 and 45.07 μg/g, respectively.
Antibacterial and mildew‐proof aramid fiber III: The chlorination mechanism through experimental and computational investigation
Authors: Wang Ziang , Zhou Bo , Fan Wuhou , Jiang Yuanzhang , Tan Lin
Published: August 2023

Heterocyclic aramid fiber (Aramid III) is an important member of the aromatic polyamide family, featured as high strength, modulus, and thermal stability. However, the erosion by microorganisms severely jeopardizes these intrinsic properties. In this study, antibacterial and mildew‐proof Aramid III was facilely prepared via chlorination, which exhibited excellent bactericidal ability (100% bactericidal rate at 104 CFU/mL) against various microorganisms while experiencing only a slight decrease (less than 1%) in mechanical and thermal properties. Furthermore, Density Functional theory (DFT) calculations of the chlorination process and NMR spectra of the model molecule BPB revealed that the preferential chlorination sites were the NH bonds on the benzimidazole ring rather than those on amide group, and a cation reaction mechanism was initially proposed based on the differences in activation energy for various reaction pathways. The antibacterial and mildew‐proof functionalization in the present study may effectively prolong the service time of Aramid III, and the revealed chlorination mechanism may provide a reference for other halamine polymers.
Nanocomposite proton conducting membranes based on sulfonated polystyrene/imidazole‐2‐acetic acid blend for direct methanol fuel cell application
Authors: Arab Kosar , Tohidian Mahdi , Shamsabadi Amirsaeed
Published: August 2023

Nanocomposite polyelectrolyte membranes based on sulfonated polystyrene (SPS) /imidazole‐2‐acetic acid (Im) blend (SPSIm), incorporated with halloysite nanotubes (HNTs) were studied for direct methanol fuel cell (DMFC) applications. Firstly, PS was sulfonated at various degrees of sulfonation (DS), and the optimum DS was selected based on hydrolytic stability. Then, SPS was blended with Im as new proton conducting sites. In addition to increasing proton conductivity, methanol permeability decreased due to the attractive interaction between Im and SO3H groups in SPS. In the next step, to introduce tortuous diffusion pathways and hence decrease the methanol crossover, halloysite nanotubes were incorporated into the SPSIm matrix. The results show that the methanol permeability of the membrane incorporated with 1 wt% HNT (SPSIm/HNT) was around 0.527 × 10−7 cm2 s−1, which showed a significant decrease compared to SPS, causing an improvement in the membrane selectivity parameter in comparison to pristine SPS membrane. Furthermore, the thermal properties, ion exchange capacity (IEC), water uptake behavior, and performance of the membranes were evaluated. Based on the results, owing to the reduced methanol permeability, acceptable power density, ease of preparation, as well as low cost, SPSIm/HNT could be considered for DMFC applications.
Development of poly(ℇ‐caprolactone)‐based composite packaging films incorporated nanofillers for enhanced strawberry quality
Authors: Eskitoros‐Togay Ş. Melda , Bulbul Y. Emre , Çanga Oymak Nurcihan , Dilsiz Nursel
Published: August 2023

The aim of the present study was to develop a packaging material for strawberry fruit by incorporating nanofiller such as graphene oxide (GO), graphene oxide modified with silane coupling agent (fGO), and titanium dioxide (TiO2) into a polycaprolactone (PCL) matrix using the solution casting method. In the first stage, graphene oxide was synthesized from graphite by the modified Hummers' method. Subsequently, the synthesized GO was modified with the silane coupling agent. PCL film, PCL/GO, PCL/fGO, PCL/GO/TiO2, and PCL/fGO/TiO2 nanocomposite films were eventually developed. The prepared films were characterized by structural, chemical, and thermal analysis by AFM, FTIR, XRD, DSC, TGA, water contact angle analysis and food packaging test. Structural and chemical analyses revealed that the synthesis and modification processes of GO were successfully achieved. The roughness values of the PCL/fGO and PCL/fGO/TiO2 films were found as 34.1 ± 1.2 nm and 43.3 ± 2.7 nm, respectively, which displayed a relatively smooth surface morphology compared to other films. The contact angle value for the PCL/fGO and PCL/fGO/TiO2 films sightly increased from 79.83° to 80.34°, respectively, with the addition of TiO2 to the matrix. The addition of GO into the polymer matrix increased the water absorption value of the PCL film to the maximum value of 19.64%; however, the addition of TiO2 nanoparticles decreased the water absorption value of the films by 14.62%. The results of the packaging test of strawberry fruit for 21 days demonstrated that the PCL/fGO/TiO2 nanocomposite film had the potential to be used as a food packaging film due to its ability to protect the freshness of strawberries.
Mainstream and special schools’ use of well‐being programmes: A regional survey
Authors: Nisar Atiyya , Hastings Richard P. , Watkins Richard C. , Williams Sharon
Published: August 2023

The incorporation of mental well‐being provision into school curricula is increasingly the focus of government policy in the UK and internationally. However, it is not clear what well‐being programmes schools provide to pupils, and how these programmes are delivered. The current study was an online survey to assess the use of whole‐school well‐being programmes in primary schools in North Wales. Normalisation Process Theory was utilised as a framework to assess normalisation of the well‐being programmes. One‐hundred and fifty‐one schools in North Wales responded to the survey. The mean number of whole‐school well‐being programmes utilised by schools was 4.59, and nine of the 10 most frequently used programmes had little or no associated evidence base. The well‐being programmes were generally perceived as normalised (i.e. everyday practice) by respondents. Implications for future practice are discussed, including the need to support schools to identify and implement evidence‐based mental well‐being provision.
Dapagliflozin improves diabetic cognitive impairment via indirectly modulating the mitochondria homeostasis of hippocampus in diabetic mice
Authors: Gui Zichen , Wang Jiawen , Zhang Yue , Wan Binbin , Ke Zhiqiang , Ren Zhanhong , Yang Xiaosong , Lei Min , Guo Xiying , Liu Xiufen , Ouyang Changhan , Wu Ninghua , Chen Qingjie
Published: August 2023

Cognitive impairment is increasingly recognized as an important comorbidity of diabetes progression; however, the underlying molecular mechanism is unclear. Dapagliflozin, an inhibitor of sodium‐glucose co‐transporter 2 (SGLT2), has shown promising effects against diabetes in rodent experiments and human clinical assays. This study aimed to determine the underlying mechanism and examine the effect of dapagliflozin on diabetic cognitive impairment. To create an in vivo model of diabetic cognitive impairment, streptozotocin (STZ)‐induced diabetic mice were used. Dapagliflozin was administered to mice for 8 weeks. The context fear condition and Morris water maze test was used to evaluate mice's behavioral change. Western blotting was used to evaluate protein expression. Hematoxylin and eosin (HE) and Nissl staining were applied to monitor morphological and structural changes. Congo red staining was performed to identify the formation of senile plaques. Mitochondria morphology was examined using a transmission electron microscope, and blood flow in the mouse cerebral cortex was measured using a laser Doppler imaging assay. Comparison to the diabetes mellitus (DM) group, the dapagliflozin group had lower glucose levels. Behavioral studies have shown that dapagliflozin can restore memory deficits in diabetic mice. The murky cell membrane edges and Nissl bodies more difficult to identify in the DM group were revealed by HE and Nissl staining, which were both improved by dapagliflozin treatment. Dapagliflozin inhibited the progression of Aβ generation and the reduced cerebral blood flow in the DM group was rescued. After dapagliflozin treatment, damaged mitochondria and lack of SGLT2 in the hippocampus and cortex of diabetic mice were repaired. Diabetes‐induced cognitive dysfunction was attenuated by dapagliflozin and the effect was indirect rather than direct.