bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphologic and functional characterization of granulocytes and macrophages in embryonic and adult zebrafish
Authors: Lieschke Graham J. , Oates Andrew C. , Crowhurst Meredith O. , Ward Alister C. , Layton Judith E.
Published: July 2002

The zebrafish is a useful model organism for developmental and genetic studies. The morphology and function of zebrafish myeloid cells were characterized. Adult zebrafish contain 2 distinct granulocytes, a heterophil and a rarer eosinophil, both of which circulate and are generated in the kidney, the adult hematopoietic organ. Heterophils show strong histochemical myeloperoxidasic activity, although weaker peroxidase activity was observed under some conditions in eosinophils and erythrocytes. Embryonic zebrafish have circulating immature heterophils by 48 hours after fertilization (hpf). A zebrafish myeloperoxidase homologue (myeloid-specificperoxidase; mpx) was isolated. Phylogenetic analysis suggested it represented a gene ancestral to the mammalian myeloperoxidase gene family. It was expressed in adult granulocytes and in embryos from 18 hpf, first diffusely in the axial intermediate cell mass and then discretely in a dispersed cell population. Comparison of hemoglobinized cell distribution,mpx gene expression, and myeloperoxidase histochemistry in wild-type and mutant embryos confirmed that the latter reliably identified a population of myeloid cells. Studies in embryos after tail transection demonstrated that mpx- and peroxidase-expressing cells were mobile and localized to a site of inflammation, indicating functional capability of these embryonic granulocytes. Embryonic macrophages removed carbon particles from the circulation by phagocytosis. Collectively, these observations have demonstrated the early onset of zebrafish granulopoiesis, have proved that granulocytes circulate by 48 hpf, and have demonstrated the functional activity of embryonic granulocytes and macrophages. These observations will facilitate the application of this genetically tractable organism to the study of myelopoiesis.
Association of the Q576R polymorphism in the interleukin-4 receptor α chain with indolent mastocytosis limited to the skin
Authors: Daley Trisha , Metcalfe Dean D. , Akin Cem
Published: July 2002

Gain-of-function mutations in c-kit, which appear to contribute to mast cell hyperplasia, have been detected in both limited and aggressive forms of mastocytosis, suggesting that other mutations or polymorphisms may contribute to the clinical phenotype. Because addition of interleukin-4 (IL-4) to mast cell cultures is reported to induce apoptosis, the hypothesis was considered that individuals carrying the gain-of-function polymorphism Q576R in the cytoplasmic domain of the α-subunit of the IL-4 receptor (IL-4R) might be relatively resistant to the gain-of-function mutation in c-kit. To assess this possibility, 36 patients with either cutaneous or systemic mastocytosis were studied for association with the Q576R polymorphism. The Q576R polymorphism was found more frequently in those with disease limited to skin and who exhibited lower levels of surrogate disease markers. These data suggest that the Q576R IL-4R α- chain polymorphism may mitigate disease expression and confer a better prognosis in patients with mastocytosis.
Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes
Authors: Raza Azra , Meyer Peter , Dutt Diya , Zorat Francesca , Lisak Laurie , Nascimben Fabiana , du Randt Morne , Kaspar Christopher , Goldberg Cathryn , Loew Jerome , Dar Saleem , Gezer Sefer , Venugopal Parameswaran , Zeldis Jerome
Published: July 2002

Thalidomide was administered to 83 patients with myelodysplastic syndrome (MDS), starting at 100 mg by mouth daily and increasing to 400 mg as tolerated. Thirty-two patients stopped therapy before 12 weeks (minimum period for response evaluation), and 51 completed 12 weeks of therapy. International Working Group response criteria for MDS were used to evaluate responses. Intent-to-treat (ITT) analysis classified all off-study patients as nonresponders. Off-study patients belonged to a higher risk category (P = .002) and had a higher percentage of blasts in their pretherapy bone marrow than patients who completed 12 weeks of therapy (P = .003). No cytogenetic or complete responses were seen, but 16 patients showed hematologic improvement, with 10 previously transfusion-dependent patients becoming transfusion independent. Responders had lower pretherapy blasts (P = .016), a lower duration of pretherapy platelet transfusions (P = .013), and higher pretherapy platelets (P = .003). Among responders, 9 had refractory anemia (RA); 5 had RA with ringed sideroblasts; and 2 had RA with excess blasts. By ITT analysis, 19% of patients (16 of 83) responded, and when only evaluable patients were analyzed, 31% (16 of 51) responded. It was concluded that thalidomide, as a single agent, is effective in improving cytopenias of some MDS patients, especially those who present without excess blasts.
The nonexpression of CD36 on reticulocytes and mature red blood cells does not modify the clinical course of patients with sickle cell anemia
Authors: Lee Ketty , Gane Pierre , Roudot-Thoraval Françoise , Godeau Bertand , Bachir Dora , Bernaudin Françoise , Cartron Jean-Pierre , Galactéros Frédéric , Bierling Philippe
Published: July 2002

It is thought that an increase in the adhesion of circulating reticulocytes to the vascular endothelium may initiate the vascular occlusion underlying the painful crises and organ failures typical of sickle cell disease (SCD). At least 2 receptors, usually present on reticulocytes, seem to be involved in this adhesion process: glycoprotein CD36 (glycoprotein IV) and integrin α4β1 (very late activation antigen–4). Recently, a high frequency of the platelet CD36–deficient phenotype was reported in black Africans. The frequency of this deficiency was similar in subjects with and without SCD. The role of CD36 in vaso-occlusion was then investigated by comparing the clinical course in 2 groups of black Africans homozygous for hemoglobin S, with and without CD36 deficiency, but similar in age, sex, geographical origin, number of α-globin genes, and β-globin gene haplotype. Flow cytometry showed that CD36 was absent from the circulating red blood cells and reticulocytes of platelet CD36–deficient individuals but present on those from patients with normal platelet CD36 expression, and that α4β1 integrin levels were similar on the reticulocytes of the 2 groups. Neither clinical severity, as evaluated by the frequency and characteristics of vaso-occlusive events, nor biological data differed significantly in the 2 groups of patients. Finally, although CD36 has been suggested to play a critical role in the pathogenesis of vaso-occlusion, this study, despite including only a small number of patients, supports the idea that the modulation of expression of a single type of adhesion molecule is insufficient to counteract the pathological process leading to vaso-occlusion in SCD patients.
Apo2L/TRAIL and Bcl-2–related proteins regulate type I interferon–induced apoptosis in multiple myeloma
Authors: Chen Quan , Gong Bendi , Mahmoud-Ahmed Ashraf S. , Zhou Aimin , Hsi Eric D. , Hussein Mohamad , Almasan Alexandru
Published: July 2002

It has been reported that interferons (IFNs) may have antitumor activity in multiple myeloma (MM). The mechanism for their effect on MM, however, remains elusive. This study shows that IFN-α and -β, but not -γ, induce apoptosis characterized by Annexin V positivity, nuclear fragmentation and condensation, and loss of clonogenicity in 3 MM cell lines (U266, RPMI-8266, and NCI-H929), and in plasma cells from 10 patients with MM. Apo2 ligand (Apo2L, also TRAIL) induction was one of the earliest events following IFN administration in U266 cells. Treatment of these cells with TRAIL, but not with Fas agonistic antibodies, induces apoptosis. Cell death induced by IFNs and Apo2L in U266 cells was partially blocked by a dominant-negative Apo2L receptor, DR5, demonstrating the functional significance of Apo2L induction. This study shows that IFNs activate caspases and the mitochondrial-dependent apoptotic pathway, possibly mediated by Apo2L production. Thus, IFN-α and -β induce cytochrome c release from mitochondria starting at 12 hours, with an amplified release seen at 48 hours. Moreover, Bid cleavage precedes the initial cytochrome c release, whereas the late, amplified cytochrome c release coincides with changes in levels of Bcl-2, Bcl-XL, and reduction of mitochondrial membrane potential. These results link the Apo2L induction and modulation of Bcl-2 family proteins to mitochondrial dysfunction. Furthermore, IFNs and Apo2L induce cell death of CD38+/CD45−/dimplasma cells, without significant effect on nonplasma blood cells, in a caspase and Bcl-2 cleavage-dependent manner. These results warrant further clinical studies with IFNs and Apo2L in MM.
COVID-19 May Protect Against the Common Cold—Here’s Why Knowing That Could Lead to Better Vaccines
Authors: Youmshajekian Lori
Published: July 2024

This Medical News article discusses new research on immune system cross-reactivity to different coronaviruses and implications for pan-coronavirus vaccines.
US State Restrictions and Excess COVID-19 Pandemic Deaths
Authors: Ruhm Christopher J.
Published: July 2024

Importance

Despite considerable prior research, it remains unclear whether and by how much state COVID-19−related restrictions affected the number of pandemic deaths in the US.

Objective

To determine how state restrictions were associated with excess COVID-19 deaths over a 2-year analysis period.

Design, Setting, and Participants

This was a cross-sectional study using state-level mortality and population data from the US Centers for Disease Control and Prevention for 2020 to 2022 compared with baseline data for 2017 to 2019. Data included the total US population, with separate estimates for younger than 45 years, 45 to 64 years, 65 to 84 years, and 85 years or older used to construct age-standardized measures. Age-standardized excess mortality rates and ratios for July 2020 to June 2022 were calculated and compared with prepandemic baseline rates. Excess death rates and ratios were then regressed on single or multiple restrictions, while controlling for excess death rates or ratios, from March 2020 to June 2020. Estimated values of the dependent variables were calculated for packages of weak vs strong state restrictions. Behavioral changes were investigated as a potential mechanism for the overall effects. Data analyses were performed from October 1, 2023, to June 13, 2024.

Exposures

Age and cause of death.

Main Outcomes

Excess deaths, age-standardized excess death rates per 100 000, and excess death ratios.

Results

Mask requirements and vaccine mandates were negatively associated with excess deaths, prohibitions on vaccine or mask mandates were positively associated with death rates, and activity limitations were mostly not associated with death rates. If all states had imposed restrictions similar to those used in the 10 most restrictive states, excess deaths would have been an estimated 10% to 21% lower than the 1.18 million that actually occurred during the 2-year analysis period; conversely, the estimates suggest counterfactual increases of 13% to 17% if all states had restrictions similar to those in the 10 least-restrictive states. The estimated strong vs weak state restriction difference was 271 000 to 447 000 deaths, with behavior changes associated with 49% to 79% of the overall disparity.

Conclusions and Relevance

This cross-sectional study indicates that stringent COVID-19 restrictions, as a group, were associated with substantial decreases in pandemic mortality, with behavior changes plausibly serving as an important explanatory mechanism. These findings do not support the views that COVID-19 restrictions were ineffective. However, not all restrictions were equally effective; some, such as school closings, likely provided minimal benefit while imposing substantial cost.
Bridging the conservation and development trade‐off? A working landscape critique of a conservancy in the Maasai Mara
Authors: Tyrrell Peter , Evans Lauren , Brehony Peadar , Wood Philippa , Karimi Rebekah , ole Kaelo Dickson , Hunter Freddie , Muiyuro Rose , Kang'ethe Esther , Perry Brian
Published: July 2024

The recent call to halt biodiversity loss by protecting half the planet has been hotly contested because of the extent to which people might be excluded from these landscapes. It is clear that incorporating landscapes that implicitly work for indigenous people is vital to achieving any sustainable targets.

We examine an attempt to balance the trade‐offs between conservation and development in Enonkishu Conservancy in the Maasai Mara, using a working landscape approach. Mobile livestock production strategies are theoretically consistent with wildlife‐based activities and can present a win‐win solution for both conservation and development. We explore the success and failings of Enonkishu's evolving attempts to achieve this: addressing the criticism of the conservation sector that it fails to learn from its mistakes.

We found that Enonkishu has had considerable positive conservation outcomes, preventing the continued encroachment of farmland and maintaining and improving rangeland health relative to the surrounding area, while maintaining diverse and large populations of wildlife and livestock.

The learning from certain ventures that failed, particularly on livestock, has created institutions and governance that, while still evolving, are more robust and relevant for conservancy members, by being fluid and inclusive.

Practical implication: Diverse revenue streams (beyond tourism, including a residential estate, livestock venture and philanthropy) enabled Enonkishu to withstand the pressures of COVID‐19. Livestock is crucial for defining the vision of the conservancy, and the institutions and governance that underpin it.
Molecular Dynamics Simulation of Uniaxial Tensile Mechanical Properties and Failure Mechanisms of MgAl2O4 Spinel
Authors: Pan Aiqiong , Wang Wenyan , Zhang Hui , Hao Shiming , Xie Jingpei , Wang Aiqin
Published: July 2024

This study employs the molecular dynamics method to examine the tensile mechanical properties and failure mechanism of MgAl2O4 spinel along [001] orientation. The results indicate that the mechanical properties of MgAl2O4 are sensitive to temperature. Young's modulus and ultimate tensile strength (UTS) of MgAl2O4 exhibit a linear decrease with increasing temperature from 100 to 2100 K. Specifically, Young's modulus decreases from 237.1 to 154.9 GPa, while the UTS decreases from 23.9 to 11.5 GPa. The failure mechanism of MgAl2O4 under uniaxial tensile loading is a brittle fracture induced by point defects. The propagation of microcracks in MgAl2O4 single crystal during tension is related to the slip band. The temperature does not have a significant effect on the direction of microcrack propagation, but it influences the crack expansion rate. In addition, the effect of strain rate on the mechanical properties of MgAl2O4 has been explored. In the range of 5 × 108 to 2 × 1010 s−1, the strain rate has almost no effect on the elastic modulus and the crack propagation direction and has little influence on the UTS. However, high strain rates delay the initiation of MgAl2O4 cracking.
Long‐Term High‐Temperature Oxidation of Al10CoCrFeNi30 High‐Entropy Alloy
Authors: Bastin Anne , Robertson Taylor , Huang Xiao , Kearsey Richard
Published: July 2024

The combined effects of high‐temperature and long‐term exposure to oxidation environment on an AlCoCrFeNi‐based high entropy alloy (HEA) are investigated. The alloy has a composition of Al10Co20Cr20Fe20Ni30 (at%) and is oxidized in lab air at 1000 °C for 1000 h to emulate working conditions and long operation cycles of gas turbines. The microstructure and oxide formation of the HEA are characterized using scanning electron microscopy, energy‐dispersive spectroscopy, and X‐ray diffraction. The performance of the HEA is compared to that of Inconel 625 and Hastelloy X and shows slower oxidation kinetics than Inconel 625 until 750 h. The HEA has the thinnest oxide layer of the three alloys and exhibits a triplex structure with a continuous Cr2O3 outer scale, a semi‐continuous Al2O3 subscale, and deep AlN precipitates. The matrix shows signs of Cr and Al depletion after 1000 h, leading to its inability to replace the degraded oxide scales that evaporated or spalled, and decreases its long‐term oxidation resistance. Overall, the HEA shows good oxidation resistance until 750 h, but may benefit from a higher Al content on the surface to form a longer‐lasting Al2O3 subscale that would remain protective beyond 750 h.
Intratumoral Microbiota as a Target for Advanced Cancer Therapeutics
Authors: Peng Fei , Hu Mengyuan , Su Zhiyue , Hu Lin , Guo Lingchuan , Yang Kai
Published: July 2024

In recent years, advancements in microbial sequencing technology have sparked an increasing interest in the bacteria residing within solid tumors and its distribution and functions in various tumors. Intratumoral bacteria critically modulate tumor oncogenesis and development through DNA damage induction, chronic inflammation, epigenetic alterations, and metabolic and immune regulation, while also influencing cancer treatment efficacy by affecting drug metabolism. In response to these discoveries, a variety of anti‐cancer therapies targeting these microorganisms have emerged. These approaches encompass oncolytic therapy utilizing tumor‐associated bacteria, the design of biomaterials based on intratumoral bacteria, the use of intratumoral bacterial components for drug delivery systems, and comprehensive strategies aimed at the eradication of tumor‐promoting bacteria. Herein, this review article summarizes the distribution patterns of bacteria in different solid tumors, examines their impact on tumors, and evaluates current therapeutic strategies centered on tumor‐associated bacteria. Furthermore, the challenges and prospects for developing drugs that target these bacterial communities are also explored, promising new directions for cancer treatment.
Mullite Mineral‐Derived Robust Solid Electrolyte Enables Polyiodide Shuttle‐Free Zinc‐Iodine Batteries
Authors: Li Fulong , Zhou Chuancong , Zhang Jie , Gao Yating , Nan Qing , Luo Junming , Xu Zhenming , Zhao Zejun , Rao Peng , Li Jing , Kang Zhenye , Shi Xiaodong , Tian Xinlong
Published: July 2024

Zinc dendrite, active iodine dissolution, and polyiodide shuttle caused by the strong interaction between liquid electrolyte and solid electrode are the chief culprits for the capacity attenuation of aqueous zinc‐iodine batteries (ZIBs). Herein, mullite is adopted as raw material to prepare Zn‐based solid‐state electrolyte (Zn‐ML) for ZIBs through zinc ion exchange strategy. Owing to the merits of low electronic conductivity, low zinc diffusion energy barrier, and strong polyiodide adsorption capability, Zn‐ML electrolyte can effectively isolate the redox reactions of zinc anode and AC@I2 cathode, guide the reversible zinc deposition behavior, and inhibit the active iodine dissolution as well as polyiodide shuttle during cycling process. As expected, wide operating voltage window of 2.7 V (vs Zn2+/Zn), high Zn2+ transference number of 0.51, and low activation energy barrier of 29.7 kJ mol−1 can be achieved for the solid‐state Zn//Zn cells. Meanwhile, high reversible capacity of 127.4 and 107.6 mAh g−1 can be maintained at 0.5 and 1 A g−1 after 3 000 and 2 100 cycles for the solid‐state Zn//AC@I2 batteries, corresponding to high‐capacity retention ratio of 85.2% and 80.7%, respectively. This study will inspire the development of mineral‐derived solid electrolyte, and facilitate its application in Zn‐based secondary batteries.
Polyamine Anabolism Promotes Chemotherapy‐Induced Breast Cancer Stem Cell Enrichment
Authors: Ji Guangyu , Liu Jia , Zhao Zhiqun , Lan Jie , Yang You , Wang Zheng , Feng Huijing , Ji Kai , Jiang Xiaofeng , Xia Huize , Wei Guangyao , Zhang Yajing , Zhang Yuhong , Du Xinlong , Wang Yawen , Yang Yuanyuan , Liu Zhaojian , Zhang Kai , Mei Qi , Sun Rong , Lu Haiquan
Published: July 2024

Breast cancer patients may initially benefit from cytotoxic chemotherapy but experience treatment resistance and relapse. Chemoresistant breast cancer stem cells (BCSCs) play a pivotal role in cancer recurrence and metastasis, however, identification and eradication of BCSC population in patients are challenging. Here, an mRNA‐based BCSC signature is developed using machine learning strategy to evaluate cancer stemness in primary breast cancer patient samples. Using the BCSC signature, a critical role of polyamine anabolism in the regulation of chemotherapy‐induced BCSC enrichment, is elucidated. Mechanistically, two key polyamine anabolic enzymes, ODC1 and SRM, are directly activated by transcription factor HIF‐1 in response to chemotherapy. Genetic inhibition of HIF‐1‐controlled polyamine anabolism blocks chemotherapy‐induced BCSC enrichment in vitro and in xenograft mice. A novel specific HIF‐1 inhibitor britannin is identified through a natural compound library screening, and demonstrate that coadministration of britannin efficiently inhibits chemotherapy‐induced HIF‐1 transcriptional activity, ODC1 and SRM expression, polyamine levels, and BCSC enrichment in vitro and in xenograft and autochthonous mouse models. The findings demonstrate the key role of polyamine anabolism in BCSC regulation and provide a new strategy for breast cancer treatment.
An Ion‐Management Membrane with Vertically Aligned Uniform Electronegative Nanochannels Toward Dendrite‐Free Lithium Metal Anodes
Authors: Zhang Qizhong , Hou Borui , Wu Xuanxuan , Li Xuanlin , Guo Zaichao , Liu Jiande , Cao Dianliang , Huang Xin , Duan Jinglai , Mo Dan , Liu Jie , Yao Huijun
Published: July 2024

Lithium (Li) metal anodes have received sustained attention due to their remarkable theoretical specific capacities and low electrochemical potentials. However, the nucleation and growth of Li dendrites during cycling have hindered their application in Li metal batteries (LMBs). As an indispensable battery component, separators offer an ideal platform for mitigating Li dendrites. Herein, an ion‐management membrane (IMM) concept utilizing polydopamine (PDA)‐modified polyetherimide track‐etched membranes (PEITEMs) is proposed. The PDA@PEITEM‐based IMM features vertically aligned uniform electronegative nanochannels, serving as ion distributors and “Li‐ion guides” to simultaneously smooth ion concentration fluctuations and accelerate Li+ selective conduction. The IMM's unique structural and chemical properties yield exceptional ionic conductivity (0.73 mS cm−1) and high Li+ transfer number (0.80) while minimizing Li+ concentration fluctuations. When employed in Li/Cu cells, the IMM facilitates a Coulombic efficiency exceeding 96% over 100 cycles at 0.5 mA cm−2. Moreover, it extends the cycle lifespan of Li/Li cells to 1 200 h at 1.0 mA cm−2. For Li/LiFePO4 cells, this approach enables a specific capacity of 146 mAh g−1, maintaining capacity retention of 79.84% after 1 000 cycles. This novel strategy for constructing free‐standing functional separators is convenient, efficient, and scalable, providing valuable insights into multifunctional separators for dendrite‐free LMBs.
Reversible Electron–Holes on O in P2‐type Na0.67Li0.1Ni0.3Mn0.6O2
Authors: Marie John‐Joseph , Jenkins Max , Chen Jun , Rees Gregory , Cellorio Veronica , Choi Jaewon , Agrestini Stefano , Garcia‐Fernandez Mirian , Zhou Ke‐Jin , House Robert A. , Bruce Peter G.
Published: July 2024

Achieving reversible O‐redox through the formation of electron–holes on O could hold the key to a new generation of high energy density Na‐ion cathodes. However, to date, it has only been demonstrated in a small handful of cathode materials and none of these materials exploit the dual benefit of high voltage transition metal redox and O‐redox, instead relying on Mn3+/4+ capacity close to 2 V vs Na+/Na. Here, a new Na‐ion cathode exhibiting electron–holes on O is demonstrated, P2‐type Na0.67Li0.1Ni0.3Mn0.6O2, which also utilizes the high voltage Ni3+/4+ redox couple to deliver the highest reported energy density among this class of compound. By employing a low Li content and avoiding honeycomb ordering within the transition metal layer, it is possible to stabilize the hole states, and the high voltage plateau is preserved in Na0.67Li0.1Ni0.3Mn0.6O2 over cycling.
In situ impacts of late‐season low temperatures on cotton (Gossypium hirsutum) fiber quality and yield on the Texas High Plains
Authors: Shumate Brooke , Maeda Murilo , Bell Jourdan , Wanjura John , Ortiz‐Pustejovsky Rebekah , Kelly Brendan
Published: July 2024

Upland cotton (Gossypium hirsutum) production is important for the economy of the Texas High Plains (THP). This region of Texas is semi‐arid and regularly experiences harsh weather conditions that can be difficult to predict. Some years, a cold front will pass through the area before local cotton crops have reached maturity and there are concerns that fiber maturation stops after these cold weather events. In 2020, fiber samples were collected at two locations on the THP (representing northern and southern cotton producing regions) before, during, and after a cold front (<10°C) moved through the area in September, which is a critical period for fiber maturation. Single boll samples were taken at New Deal, TX (representing a southern location) in the first position from nodes 5, 8, and 11. At Etter, TX (representing a northern location), 30‐boll bulk samples were taken from first position bolls on nodes 5, 8, and 11. Advanced fiber information system testing determined the fiber quality of single boll samples. Lint weight in both locations continued to increase despite the cool temperatures. At New Deal, upper quartile length, length, short fiber content, seed coat neps, fineness, and maturity all saw significant improvements from before to after the cold front. This indicates that the bolls continued developing after exposure to cool temperatures on the THP.
Herbage mass responses to sod suppression with glyphosate in pastures interseeded with sorghum × sudangrass
Authors: Jenkins Matthew , Hillhouse Heidi , Guretzky John A.
Published: July 2024

Interseeding annual warm‐season forages into perennial cool‐season grasses may increase herbage mass and quality. Yet, methods to do so successfully remain elusive. From 2020 to 2022, we conducted an experiment that evaluated herbage mass responses to sod suppression after interseeding sorghum × sudangrass [Sorghum bicolor (L.) Moench × S. bicolor (L.) Moench ssp. drummondii (Nees ex Steud.) de Wet & Harlan] in three N‐fertilized and three mixed‐legume smooth bromegrass (Bromus inermis Leyss.) pastures. Sod suppression treatments included glyphosate [N‐(phosphonomethyl) glycine] applications of 0, 0.55, 1.10, 1.65, and 2.20 kg ha−1 on pastures that were heavily grazed in two rotational stocking periods in spring and an additional 0 kg ha−1 glyphosate control where herbage was stockpiled throughout spring, mowed, and removed before interseeding sorghum × sudangrass. In herbage samples collected 8 weeks after treatment, perennial grass mass showed exponential decay responses as glyphosate rate increased, while sorghum × sudangrass, weedy grass, and total herbage mass showed logistic growth responses. Sorghum × sudangrass reached a high of 2316 kg ha−1 as glyphosate rate increased to 1.65 kg ha−1 while weedy grass mass continued to increase as glyphosate rate increased to 2.20 kg ha−1. Reduced perennial grass mass in herbage samples collected the next spring indicated the presence of a tradeoff between increasing summer herbage now and reducing next spring herbage later with glyphosate application after interseeding sorghum × sudangrass. We concluded practitioners should not use glyphosate for sod suppression before interseeding warm‐season annual forages into perennial cool‐season grass pastures.
School‐based racial segregation, social support, and late‐life cognitive function in the Study of Healthy Aging in African Americans (STAR)
Authors: Gutierrez Sirena , Whitmer Rachel A. , Soh Yenee , Peterson Rachel , George Kristen M. , Lor Yi , Barnes Lisa L. , Mayeda Elizabeth Rose , Allen Isabel E. , Torres Jacqueline M. , Glymour M. Maria , Gilsanz Paola
Published: July 2024

INTRODUCTION

School‐based social support for Black students may mediate or modify the association between school segregation and late‐life cognition.

METHODS

Study of Healthy Aging in African Americans participants (n = 574) reported segregated school attendance and school‐based social support. Associations of segregated schooling with domain‐specific cognitive outcomes and effect modification or mediation by school‐based social support were evaluated with linear mixed models.

RESULTS

Segregated school attendance was associated with increased likelihood of school‐based social support. Segregated (vs. desegregated in 6th grade) school attendance was associated with lower executive function (β = −0.18 [−0.34, −0.02]) and semantic memory z‐scores (β = −0.31 [−0.48, −0.13]). Social support did not mediate these associations. Estimates for segregated school attendance were attenuated among those who felt supported, although there was limited evidence of statistically significant effect modification.

DISCUSSION

Early‐childhood school segregation was associated with poorer cognitive function. Sources of resilience within racialized educational experiences should be further evaluated to bridge inequities.

Highlights

School segregation is a form of structural racism that affected the educational experiences of Black youth with potentially lasting consequences for healthy brain aging.

Black students who attended a segregated school experienced greater school‐based social support, which may highlight a potential source of resilience and resistance against the effects of racism‐related stressors on cognitive function.

The estimated adverse association between attending a segregated school on cognition was larger for students without an adult at school who cared about them versus those with an adult at school who cared about them, but estimates were imprecise.
Low‐Dispersity Polymers via Free Radical Alternating Copolymerization: Effects of Charge‐Transfer‐Complexes
Authors: Gu Yu , Zhang Zexi , Gao Tianyi , Gómez‐Bombarelli Rafael , Chen Mao
Published: July 2024

Alternating copolymers are crucial for diverse applications. While dispersity (Ð, also known as molecular weight distribution, MWD) influences the properties of polymers, achieving low dispersities in alternating copolymers poses a notable challenge via free radical polymerizations (FRPs). In this work, we demonstrated an unexpected discovery that dispersities are affected by the participation of charge transfer complexes (CTCs) formed between monomer pairs during free radical alternating copolymerization, which have inspired the successful synthesis of various alternating copolymers with low dispersities (>30 examples, Ð=1.13–1.39) under visible‐light irradiation. The synthetic method is compatible with binary, ternary and quaternary alternating copolymerizations and is expandable for both fluorinated and non‐fluorinated monomer pairs. DFT calculations combined with model experiments indicated that CTC‐absent reaction exhibits higher propagation rates and affords fewer radical terminations, which could contribute to low dispersities. Based on the integration of Monte Carlo simulation and Bayesian optimization, we established the relationship map between FRP parameter space and dispersity, further suggested the correlation between low dispersities and higher propagation rates. Our research sheds light on dispersity control via FRPs and creates a novel platform to investigate polymer dispersity through machine learning.
Multifunctional Self‐Assembled Bio‐Interfacial Layers for High‐Performance Zinc Metal Anodes
Authors: Lu Jiahui , Wang Tianyi , Yang Jian , Shen Xin , Pang Huan , Sun Bing , Wang Guoxiu , Wang Chengyin
Published: July 2024

Rechargeable aqueous zinc‐ion (Zn‐ion) batteries are widely regarded as important candidates for next‐generation energy storage systems for low‐cost renewable energy storage. However, the development of Zn‐ion batteries is currently facing significant challenges due to uncontrollable Zn dendrite growth and severe parasitic reactions on Zn metal anodes. Herein, we report an effective strategy to improve the performance of aqueous Zn‐ion batteries by leveraging the self‐assembly of bovine serum albumin (BSA) into a bilayer configuration on Zn metal anodes. BSA′s hydrophilic and hydrophobic fragments form unique and intelligent ion channels, which regulate the migration of Zn ions and facilitate their desolvation process, significantly diminishing parasitic reactions on Zn anodes and leading to a uniform Zn deposition along the Zn (002) plane. Notably, the Zn||Zn symmetric cell with BSA as the electrolyte additive demonstrated a stable cycling performance for up to 2400 hours at a high current density of 10 mA cm−2. This work demonstrates the pivotal role of self‐assembled protein bilayer structures in improving the durability of Zn anodes in aqueous Zn‐ion batteries.
Cu‐Catalyzed Enantioselective Borylative Desymmetrization of 1‐Vinyl Cyclobutanols and Axial‐to‐Point Chirality Transfer in a Diastereoconvergent/Stereoretentive Allylation Scenery
Authors: Hurtado Josebe , Iragorri Nerea , Reyes Efraim , Vicario Jose L. , Fernández Elena
Published: July 2024

Cu‐catalyzed asymmetric allylic borylation of 3,3’‐disubstituted 1‐vinylcyclobutan‐1‐ols renders axially chiral allylborane systems, with high asymmetric induction for both enantiomers, by precise selection of the cis or trans substrate. The enantioenriched alkylidenecyclobutanes served as chiral platform to prove the conceptually challenging transference of the axial‐to‐point chirality through two new stereocenters and one pseudoasymmetric carbon generated via diastereoconvergent allylation of aldehydes, without enantioselective erosion.
Deciphering Pauling's Third Rule: Uncovering Strong Anharmonicity and Exceptionally Low Thermal Conductivity in TlAgSe for Thermoelectrics
Authors: Pathak Riddhimoy , Paul Sayan , Das Subarna , Das Anustoop , Pati Swapan K. , Biswas Kanishka
Published: July 2024

The elucidation of chemical bonding, coupled with an exploration of the correlated dynamics of constituent atoms, is essential for unravelling the underlying mechanism responsible for low lattice thermal conductivity (κL) exhibited by a crystalline solid, which is essential for thermoelectrics and thermal barrier coatings. In this regard, Pauling's third empirical rule, which deals with the cationic repulsion due to proximity in the face or edge shared polyhedra in a crystal structure, can bring about the lattice instability required to suppress the κL. Here, we demonstrate the presence of such instability in a ternary selenide, TlAgSe, leading to a ultra‐low κL of 0.17 W/m.K at 573 K. Our study reveals the instability arising from Ag−Ag repulsion within edge‐shared AgSe4 tetrahedra through investigation of the local structure using synchrotron X‐ray pair distribution function (PDF) analysis and supported by first‐principles density functional theory calculations. We observe correlation between weakening in the Ag and the Tl‐sublattice, providing direct experimental evidence of Pauling's third empirical rule. The correlated rattling of Ag and Tl induces a highly anharmonic lattice and low energy optical phonons, resulting in suppressed sound velocity and ultralow κL in TlAgSe. The electronic origin of soft and anharmonic lattice is the presence of filled antibonding states in the valence band near the Fermi level constructed by Ag(4d)−Se(4p) and Tl(6s)−Se(4p) interactions. This work demonstrates that the evidence of dynamic distortion in a crystal lattice is governed by the third empirical rule given by Pauling, which can act as a potential new strategy for diminishing κL in crystalline solids.
Electrolyte Composition‐Dependent Product Selectivity in CO2 Reduction with a Porphyrinic Metal–Organic Framework Catalyst
Authors: Pu Si‐Hua , Huang Tao , Si Duan‐Hui , Sun Meng‐Jiao , Wang Wen‐Wen , Zhang Teng , Cao Rong
Published: July 2024

A copper porphyrin‐derived metal–organic framework electrocatalyst, FICN‐8, was synthesized and its catalytic activity for CO2 reduction reaction (CO2RR) was investigated. FICN‐8 selectively catalyzed electrochemical reduction of CO2 to CO in anhydrous acetonitrile electrolyte. However, formic acid became the dominant CO2RR product with the addition of a proton source to the system. Mechanistic studies revealed the change of major reduction pathway upon proton source addition, while catalyst‐bound hydride (*H) species was proposed as the key intermediate for formic acid production. This work highlights the importance of electrolyte composition on CO2RR product selectivity.
Regulating chondrocyte senescence through substrate stiffness modulation
Authors: Wang Juan , Dai Juan , Shen Xingyu , Zhu Jianfei , Pang Xiangchao , Lin Zhaowei , Tang Bin
Published: July 2024

Chondrocytes, the resident cells of articular cartilage, play a vital role in tissue maintenance and regeneration. Recent studies have highlighted chondrocyte senescence as a key contributor to cartilage dysfunction. In this study, we investigated the influence of substrate stiffness on chondrocyte senescence using polydimethylsiloxane (PDMS) substrates with varying stiffness ratios (1:5, 1:20, and 1:60). After culturing chondrocytes on these substrates, we found that softer substrates (1:60) significantly reduced chondrocyte senescence, as evidenced by a decrease in senescence‐associated β‐galactosidase (SA‐β‐gal) activity by 33% compared with stiffer substrates (1:5). Furthermore, quantitative real‐time polymerase chain reaction (PCR) analysis revealed that chondrocytes cultured on softer substrates exhibited lower expression levels of senescence‐related genes (e.g., p16INK4a) and matrix‐degrading enzymes (e.g., MMP13). These findings suggest that substrate stiffness plays a critical role in regulating chondrocyte senescence and could potentially inform the design of scaffolds for cartilage tissue engineering.
CAPE derivatives: Multifaceted agents for chronic wound healing
Authors: Balaha Marwa , Cataldi Amelia , Ammazzalorso Alessandra , Cacciatore Ivana , De Filippis Barbara , Di Stefano Antonio , Maccallini Cristina , Rapino Monica , Korona‐Glowniak Izabela , Przekora Agata , di Giacomo Viviana
Published: July 2024

Chronic wounds significantly impact the patients' quality of life, creating an urgent interdisciplinary clinical challenge. The development of novel agents capable of accelerating the healing process is essential. Caffeic acid phenethyl ester (CAPE) has demonstrated positive effects on skin regeneration. However, its susceptibility to degradation limits its pharmaceutical application. Chemical modification of the structure improves the pharmacokinetics of this bioactive phenol. Hence, two novel series of CAPE hybrids were designed, synthesized, and investigated as potential skin regenerative agents. To enhance the stability and therapeutic efficacy, a caffeic acid frame was combined with quinolines or isoquinolines by an ester (1a–f) or an amide linkage (2a–f). The effects on cell viability of human gingival fibroblasts (HGFs) and HaCaT cells were evaluated at different concentrations; they are not cytotoxic, and some proved to stimulate cell proliferation. The most promising compounds underwent a wound‐healing assay in HGFs and HaCaT at the lowest concentrations. Antimicrobial antioxidant properties were also explored. The chemical and thermal stabilities of the best compounds were assessed. In silico predictions were employed to anticipate skin penetration capabilities. Our findings highlight the therapeutic potential of caffeic acid phenethyl ester (CAPE) derivatives 1a and 1d as skin regenerative agents, being able to stimulate cell proliferation, control bacterial growth, regulate ROS levels, and being thermally and chemically stable. An interesting structure–activity relationship was discussed to suggest a promising multitargeted approach for enhanced wound healing.
A metabolomics study on the mechanisms of Gardeniae fructus against α‐naphthylisothiocyanate‐induced cholestatic liver injury
Authors: Cao Yangang , Li Shujing , Zhang Zhenkai , Zeng Mengnan , Zheng Xiaoke , Feng Weisheng
Published: July 2024

Gardeniae fructus (GF) is known for its various beneficial effects on cholestatic liver injury (CLI). However, the biological mechanisms through which GF regulates CLI have not been fully elucidated. This study aimed to explore the potential mechanisms of GF against α‐naphthylisothiocyanate (ANIT)‐induced CLI. First, HPLC technology was used to analyze the chemical profile of the GF extract. Second, the effects of GF on serum biochemical indicators and liver histopathology were examined. Lastly, metabolomics was utilized to study the changes in liver metabolites and clarify the associated metabolic pathways. In chemical analysis, 10 components were identified in the GF extract. GF treatment regulated serum biochemical indicators in ANIT‐induced CLI model rats and alleviated liver histological damage. Metabolomics identified 26 endogenous metabolites as biomarkers of ANIT‐induced CLI, with 23 biomarkers returning to normal levels, particularly involving primary bile acid biosynthesis, glycerophospholipid metabolism, tryptophan metabolism, and arachidonic acid metabolism. GF shows promise in alleviating ANIT‐induced CLI by modulating multiple pathways.
Underrecognition of migraine‐related stigmatizing attitudes and social burden: Results of the OVERCOME Japan study
Authors: Igarashi Hisaka , Komori Mika , Ueda Kaname , Zagar Anthony J. , Jaffe Dena H. , Matsumori Yasuhiko , Takeshima Takao , Hirata Koichi
Published: July 2024

Introduction

Migraine‐related stigma (MiRS) and social burden is increasingly recognized. We assessed perspectives and attitudes toward migraine in people with and without migraine in Japan.

Methods

OVERCOME (Japan) was a cross‐sectional, population‐based web survey of people with and without migraine (July−September 2020). People with migraine were individuals who met the modified International Classification of Headache Disorders criteria or had self‐reported physician‐diagnosed migraine. People without migraine were selected per quota sampling to represent the Japanese adult population. People with migraine reported their experiences on stigma and social burden and answered how frequently they experienced stigma using the MiRS questionnaire. Associations between MiRS and disability and MiRS and interictal burden were examined using the migraine disability assessment and Migraine Interictal Burden Scale‐4. People without migraine reported their experiences and attitudes toward people with migraine by answering an 11‐item attitudinal migraine questionnaire.

Results

A total of 17,071 and 2008 people with and without migraine, respectively, completed the survey. Overall, 11,228 (65.8%) respondents with migraine reported that they have never experienced stigma or burden; however, of the 12,383 employed respondents, 5841 (47.2%) reported that their current employers are not “extremely” or “very” understanding about their conditions. Moreover, ∼30%−40% of respondents “sometimes,” “often,” or “very often” hid their migraine from others. The proportion of respondents who experienced stigma often or very often, as assessed by MiRS, was 16.5%; this increased with the increasing number of monthly migraine headache days. The proportion of respondents with moderate‐to‐severe disability and interictal burden increased with increasing stigma. Among respondents without migraine, the proportion holding a stigmatizing attitude toward those with migraine was low (<15%); ∼80% had never experienced work‐ or family‐related stigma or burden.

Conclusion

MiRS and burden exist but may be hidden and underrecognized in Japan. Disease awareness and education may be important to prevent and reduce stigma and burden.
Enhanced production of isobutyl and isoamyl acetate using Yarrowia lipolytica
Authors: Koshiba Ayumi , Nakano Mariko , Hirata Yuuki , Konishi Rie , Matsuoka Yuta , Miwa Yuta , Mori Ayana , Kondo Akihiko , Tanaka Tsutomu
Published: July 2024

Short‐chain esters, particularly isobutyl acetate and isoamyl acetate, hold significant industrial value due to their wide‐ranging applications in flavors, fragrances, solvents, and biofuels. In this study, we demonstrated the biosynthesis of acetate esters using Yarrowia lipolytica as a host by feeding alcohols to the yeast culture. Initially, we screened for optimal alcohol acyltransferases for ester biosynthesis in Y. lipolytica. Strains of Y. lipolytica expressing atf1 from Saccharomyces cerevisiae, produced 251 or 613 mg/L of isobutyl acetate or of isoamyl acetate, respectively. We found that introducing additional copies of ATF1 enhanced ester production. Furthermore, by increasing the supply of acetyl‐CoA and refining the culture conditions, we achieved high production of isoamyl acetate, reaching titers of 3404 mg/L. We expanded our study to include the synthesis of a range of acetate esters, facilitated by enriching the culture medium with various alcohols. This study underscores the versatility and potential of Y. lipolytica in the industrial production of acetate esters.
Pyrazole, Pyrazoline, and Fused Pyrazole Derivatives: New Horizons in EGFR‐Targeted Anticancer Agents
Authors: Hosamani Ketan R , K Hemalatha , Pal Rohit , Matada Gurubasavaraja Swamy Purawarga , B Kumaraswamy , I Aayishamma , Aishwarya Nimmagadda Venkata Satya Sai
Published: July 2024

Pyrazole and its derivatives remain popular heterocycles in drug research, design, and development. Several drugs include the pyrazole scaffold, such as ramifenazone, ibipinabant, antipyrine, and axitinib, etc. They have been extensively studied by the scientific community and are said to have a wide range of biological activity, especially anticancer agents targeting EGFR. Overexpression of EGFR signalling promotes tumor growth by inhibiting apoptosis. EGFR dysfunction has been described in multiple cancers, including colon, head and neck, NSCLC, colon, liver, breast, and ovarian cancer. As a result, EGFR represents a prospective target for cancer treatment. Several anti‐EGFR drugs are thriving, notably dacomitinib, afatinib, erlotinib, gefitinib, and osimertinib. However, almost all currently available anti‐EGFR drugs have limited therapeutic effectiveness due to a lack of selectivity as well as substantial side effects. Furthermore, aberrant EGFR signalling across numerous human malignancies/carcinomas is impeded by gene amplification, protein overexpression, mutations, or in‐frame deletions, making EGFR‐induced cancer treatment challenging. To overcome such, novel therapeutic anti‐EGFR drugs with high efficacy and minimal toxicity are required. To battle cancer and therapeutic resistance to EGFR inhibitors, pyrazole, pyrazoline, and their derivatives have been investigated as a viable pharmacophore for the development of new drugs with better potency, lesser toxicity, and favourable pharmacokinetic characteristics. The present investigation covers the examination of progress toward anti‐cancer therapies targeting EGFR via pyrazole, pyrazoline, and fused pyrazole‐based compounds. The current study also represents inclusive data on pyrazole‐based marketed drugs as well as therapeutic candidates undergoing preclinical and clinical development. Lastly, we have discussed recent advances in the medicinal chemistry of pyrazole‐based derivatives with their anti‐EGFR significance for the eradication of various cancers and provide the direction toward structure‐activity relationship (SAR), including mechanistic studies.