bluuebunny/crossref_metadata_2025 huggingface dataset:
Neighboring Effect‐Initiated Supramolecular Nanocomplex with Sequential Infiltration as Irreversible Apoptosis Inducer for Synergetic Chemo‐Immunotherapy
Authors: Ye Mengjie , Hu Junfeng , Han Linlin , Zhang Hengbo , Xue Peng , Kang Yuejun , Bai Shuang , Xu Zhigang
Published: August 2024

Chemotherapy‐based combination regimens are recommended as first‐line treatment for colorectal cancer. However, multidrug resistance (MDR) and limited drug infiltration in tumor microenvironment remain critical challenges. Herein, a pH/redox dual activated supramolecular DAS@CD‐OxPt (IV) nanoparticles (NPs) via host‐guest molecular recognition to achieve relay drugs delivery of active oxaliplatin (OxPt (IV)) and Src inhibitor dasatinib (DAS) between tumor cells is developed. DAS@CD‐OxPt (IV) NPs exhibit prolonged circulation in the blood and intra‐tumoral retention. Triggered by the endo/lysosome (pH 5.0), flexible DAS@CD‐OxPt (IV) NPs exhibited proton‐driven in situ assembly to form nanofiber in tumor cells. Dual chemotherapeutic agents released from DAS@CD‐OxPt (IV) NPs synergistically cause irreversible DNA damage by blocking p53‐mediated DNA repair. Supramolecular nanofibers can further serve as the “ammunition depot” to continuously release drugs from dying cells and transport them into neighboring tumor cells, leading to domino‐like cell death and enhanced immunogenicity. Furthermore, DAS@CD‐OxPt (IV) NPs combined with immune checkpoint blockade (ICB) therapy strikingly suppress CT26 tumor growth and pulmonary metastasis.
Surface Acoustic Wave‐Enhanced Multi‐View Acoustofluidic Rotation Cytometry (MARC) for Pre‐Cytopathological Screening
Authors: Zhang Xiaoyan , Dumčius Povilas , Mikhaylov Roman , Qi Jiangfa , Stringer Mercedes , Sun Chao , Nguyen Van Dien , Zhou You , Sun Xianfang , Liang Dongfang , Liu Dongge , Yan Bing , Feng Xi , Mei Changjun , Xu Cong , Feng Mingqian , Fu Yongqing , Clayton Aled , Zhi Ruicong , Tian Liangfei , Dong Zhiqiang , Yang Xin
Published: August 2024

Cytopathology, crucial in disease diagnosis, commonly uses microscopic slides to scrutinize cellular abnormalities. However, processing high volumes of samples often results in numerous negative diagnoses, consuming significant time and resources in healthcare. To address this challenge, a surface acoustic wave‐enhanced multi‐view acoustofluidic rotation cytometry (MARC) technique is developed for pre‐cytopathological screening. MARC enhances cellular morphology analysis through comprehensive and multi‐angle observations and amplifies subtle cell differences, particularly in the nuclear‐to‐cytoplasmic ratio, across various cell types and between cancerous and normal tissue cells. By prioritizing MARC‐screened positive cases, this approach can potentially streamline traditional cytopathology, reducing the workload and resources spent on negative diagnoses. This significant advancement enhances overall diagnostic efficiency, offering a transformative vision for cytopathological screening.
The Multi‐Functional Third Acceptor Realizes the Synergistic Improvement in Photovoltaic Parameters and the High‐Ratio Tolerance of Ternary Organic Photovoltaics
Authors: Liu Yuhao , Zhan Lingling , Li Zhongjie , Jiang Hang , Qiu Huayu , Sun Xiaokang , Hu Hanlin , Sun Rui , Min Jie , Yu Jinyang , Fu Weifei , Yin Shouchun , Chen Hongzheng
Published: August 2024

The ternary strategy proves effective for breakthroughs in organic photovoltaics (OPVs). Elevating three photovoltaic parameters synergistically, especially the proportion‐insensitive third component, is crucial for efficient ternary devices. This work introduces a molecular design strategy by comprehensively analyzing asymmetric end groups, side‐chain engineering, and halogenation to explore the outstanding optoelectronic properties of the proportion‐insensitive third component in efficient ternary systems. Three asymmetric non‐fullerene acceptors (BTP‐SA1, BTP‐SA2, and BTP‐SA3) are synthesized based on the Y6 framework and incorporated as the third component into the D18:Y6 binary system. BTP‐SA3, featuring asymmetric terminal (difluoro‐indone and dichloride‐cyanoindone terminal), with branched alkyl side chains, exhibited high open‐circuit voltage (VOC), balanced crystallinity and compatibility, achieving synergistic enhancements in VOC (0.862 V), short circuit‐current density (JSC, 27.52 mA cm−2), fill fact (FF, 81.01%), and power convert efficiency (PCE, 19.19%). Device based on D18/Y6:BTP‐SA3 (layer‐by‐layer processed) reached a high efficiency of 19.36%, demonstrating a high tolerance for BTP‐SA3 (10–50%). This work provides novel insights into optimizing OPVs performances in multi‐component systems and designing components with enhanced tolerance.
Decolorization of Lignin for High‐Resolution 3D Printing of High Lignin‐Content Composites
Authors: Böcherer David , Montazeri Ramin , Li Yuanyuan , Tisato Silvio , Hambitzer Leonhard , Helmer Dorothea
Published: August 2024

Lignin, one of the most abundant biomaterials and a large‐scale industrial waste product, is a promising filler for polymers as it reduces the amount of fossil resources and is readily available. 3D printing is well‐known for producing detailed polymer structures in small sizes at low waste production. Especially light‐assisted 3D printing is a powerful technique for production of high‐resolution structures. However, lignin acts as a very efficient absorber for UV and visible light limiting the printability of lignin composites, reducing its potential as a high‐volume filler. In this work, the decolorization of lignin is presented for high‐resolution 3D printing of biocomposites with lignin content up to 40 wt.%. Organosolv lignin (OSL) is decolorized by an optimized low‐energy process of acetylation and subsequent UV irradiation reducing the UV absorbance by 71%. By integration of decolorized lignin into bio‐based tetrahydrofurfuryl acrylate (THFA), a lignin content of 40 wt.% and a resolution of 250 µm is achieved. Due to the reinforcing properties of lignin, the stiffness and strength of the material is increased by factors of 15 and 2.3, respectively. This work paves the way for the re‐use of a large amount of lignin waste for 3D printing of tough materials at high resolution.
Monoclinic Silver Vanadate (Ag0.33V2O5) as a High‐Capacity Stable Cathode Material for Aqueous Manganese Batteries
Authors: Lee Hyeonjun , Lee Hyungjin , Pyun Jangwook , Hong Seung‐Tae , Chae Munseok S.
Published: August 2024

Aqueous rechargeable metal batteries have recently garnered considerable attention owing to their low cost, sufficient capacity, and the use of non‐flammable water‐based electrolytes. Among them, manganese batteries are particularly favored because of their stability, abundance, affordability, and high energy density. Despite their advantages, Mn storage host structures remain underexplored. Therefore, developing innovative host materials is crucial for advancing this field. In this paper, the study reports for the first time, the use of Ag0.33V2O5 as a cathode material in aqueous manganese batteries. The study explains the displacement/intercalation behavior of manganese and silver using electrochemical, structural, and spectroscopic analyses. Additionally, it is shown that cation (Ag+, Mn2+, H+) diffusion pathways can be simulated using diffusion‐barrier calculations. Finally, the study demonstrates high‐performance manganese batteries that exhibit a remarkable reversible capacity of ≈261.9 mAh g−1 at a current of 0.1 A g−1 and an excellent cycle retention of 69.1% after 2000 cycles at a current density of 1.5 A/g. The findings of this study contribute to the advancement of aqueous manganese battery technology, offering a promising pathway for developing safer, more cost‐effective, and high‐performance energy storage systems.
Miniature Modular Reconfigurable Underwater Robot Based on Synthetic Jet
Authors: Wang Dehong , Zhang Fanheng , Zhang Shijing , Liu Daqing , Li Jing , Chen Weishan , Deng Jie , Liu Yingxiang
Published: August 2024

Modular reconfigurable robots exhibit prominent advantages in the reconnaissance and exploration tasks within unstructured environments for their characteristics of high adaptability and high robustness. However, due to the limitations in locomotion mechanism and integration requirements, the modular design of miniature robots in the aquatic environment encounters significant challenges. Here, a modular strategy based on the synthetic jet principle is proposed, and a modular reconfigurable robot system is developed. Specialized bottom and side jet actuators are designed with vibration motors as excitation sources, and a motion module is developed incorporating the jet actuators to realize three‐dimensional agile motion. Its linear, rotational, and ascending motion speeds reach 70.7 mm s−1, 3.3 rad s−1, and 28.7 mm s−1, respectively. The module integrates the power supply, communication, and control system with a small size of 48 mm × 38 mm × 38 mm, which ensures a wireless controllable motion. Then, various configurations of the multi‐module robot system are established with corresponding motion schemes, and the experiments with replaceable intermediate modules are further conducted to verify the transportation and image‐capturing functions. This work demonstrates the effectiveness of synthetic jet propulsion for aquatic modular reconfigurable robot systems, and it exhibits profound potential in future underwater applications.
Surface Formamidine Cation Immobilization for Efficient FA‐Based Perovskites Solar Cells
Authors: Liu Hanfeng , Liu Tiantian , Wang Xingtao , Hu Guangcai , Zheng Baochao , Yu Xuegong , Wang Yong , Yang Deren
Published: August 2024

State‐of‐the‐art perovskite solar cells (PSCs) continue to encounter stability challenges throughout their current commercialization process, primarily due to the instable organic components. Especially, surface (interface) imperfections, like the undercoordinated Pb2+ and halide sites, further compromise the confinement of organic cations at the surface (interface) and provide a rapid pathway for ion migration and volatilization, decreasing stability and efficiency. Herein, the study has developed a surface Formamidine (FA) cation immobilization strategy through hydrogen bond effect, achieved by a post‐treatment of piperazine dihydrochloride (PDCl2), to obtain stable FA‐based perovskites. The piperazine can immobilize surface FA+ cation through hydrogen bond. Moreover, the post‐treatment of PDCl2 can induce surface Cl– doping to establish strong coordinating bond with the uncoordinated Pb2+, reducing the imperfections of surface octahedral cage. Such a synergistic effect effectively constrains surface FA+ cations, simultaneously alleviates surface lattice stress. Because of improved surface properties, the resultant perovskite demonstrates not only outstanding light/thermal stability, but also more pronounced n‐type characteristics and uniform potential distribution for improving charge transfer dynamics. Finally, the champion PSCs exhibit a significantly enhanced efficiency from 23.15% to 25.52%. Moreover, these PSCs exhibit excellent stability: retain 91% of their initial efficiency after over 1000 h maximum power point test.
Fasting and calorie restriction modulate age‐associated immunosenescence and inflammaging
Authors: Tizazu Anteneh Mehari
Published: August 2024

Aging is a multifaceted process impacting cells, tissues, organs, and organ systems of the body. Like other systems, aging affects both the adaptive and the innate components of the immune system, a phenomenon known as immunosenescence. The deregulation of the immune system puts elderly individuals at higher risk of infection, lower response to vaccines, and increased incidence of cancer. In the Western world, overnutrition has increased the incidence of obesity (linked with chronic inflammation) which increases the risk of metabolic syndrome, cardiovascular disease, and cancer. Aging is also associated with inflammaging a sterile chronic inflammation that predisposes individuals to age‐associated disease. Genetic manipulation of the nutrient‐sensing pathway, fasting, and calorie restriction (CR) has been shown to increase the lifespan of model organisms. As well in humans, fasting and CR have also been shown to improve different health parameters. Yet the direct effect of fasting and CR on the aging immune system needs to be further explored. Identifying the effect of fasting and CR on the immune system and how it modulates different parameters of immunosenescence could be important in designing pharmacological or nutritional interventions that slow or revert immunosenescence and strengthen the immune system of elderly individuals. Furthermore, clinical intervention can also be planned, by incorporating fasting or CR with medication, chemotherapy, and vaccination regimes. This review discusses age‐associated changes in the immune system and how these changes are modified by fasting and CR which add information on interventions that promote healthy aging and longevity in the growing aging population.
A Metal‐Free Amination of 1,2‐Diaza‐1,3‐dienes Using Hydrazine Hydrate Through N−N Bond Cleavage
Authors: Kumar Abhishek , Jaiswal Arvind Kumar , Kushawaha Ajay Kishor , Singh Anushka , Kant Ruchir , Shukla Sanjeev K. , Sashidhara Koneni V.
Published: August 2024

Herein, we have developed a metal‐free, atom‐economical, intrinsically sustainable approach for synthesizing unprotected 4,5‐diamino pyrazoles from readily available 1,2‐diaza‐1,3‐dienes. This approach utilizes inexpensive hydrazine hydrate as the aminating source. Further, we have explored the reactivity of 4,5‐diamino pyrazole to synthesize fused pyrazolo[3,4‐d]‐1,2,3‐triazole heterocyclic compounds. We have also successfully demonstrated the synthetic utility of this methodology in synthesizing two drug analogs: analgesic difenamizole and anti‐psychotic CDPPB. The role of the phenyl ring of 3‐substituted‐1,2‐diaza‐1,3‐diene was explained with the help of control experimental and density functional theory (DFT) computation studies.
Lacosamide and Levetiracetam Are Not Toxic to the Developing Mouse Brain
Authors: Noguchi Kevin K. , Palmer Cory W. , Fuhler Nicole A. , Neblock Eric , Fotedar Maya , Ikonomidou Chrysanthy
Published: August 2024

Many antiseizure medications cause apoptotic cell death in developing brains. The newer antiseizure medication lacosamide is increasingly used in neonates and infants. Neurotoxicity of lacosamide and its combination with levetiracetam was studied in neonatal mice. Animals received single or repeat injections of saline, phenobarbital (75mg/kg), lacosamide (20–40mg/kg), levetiracetam (100mg/kg), lacosamide (40mg/kg) + levetiracetam (100mg/kg) and euthanized at 6 to 30 hours. Cells undergoing apoptosis were increased in the brains of phenobarbital‐treated animals. Densities of apoptotic profiles following lacosamide and levetiracetam treatment did not differ from saline‐treated controls. Findings suggest that lacosamide, levetiracetam and their combination do not cause apoptosis in developing mouse brains. ANN NEUROL 2024;96:812–818
Reversible Local Protonation‐Deprotonation: Tuning Stimuli‐Responsive Circularly Polarized Luminescence in Chiral Hybrid Zinc Halides for Anti‐Counterfeiting and Encryption
Authors: Liu Dan‐Yang , Xiong Lin‐Yuan , Dong Xi‐Yan , Han Zhen , Liu Hua‐Li , Zang Shuang‐Quan
Published: August 2024

Precise control over the organic composition is crucial for tailoring the distinctive structures and properties of hybrid metal halides. However, this approach is seldom utilized to develop materials that exhibit stimuli‐responsive circularly polarized luminescence (CPL). Herein, we present the synthesis and characterization of enantiomeric hybrid zinc bromides: biprotonated ((R/S)‐C12H16N2)ZnBr4 ((R/S‐LH2)ZnBr4) and monoprotonated ((R/S)‐C12H15N2)2ZnBr4 ((R/S‐LH1)2ZnBr4), derived from the chiral organic amine (R/S)‐2,3,4,9‐Tetrahydro‐1H‐carbazol‐3‐amine ((R/S)‐C12H14N2). These compounds showcase luminescent properties; the zero‐dimensional biprotonated form emits green light at 505 nm, while the monoprotonated form, with a pseudo‐layered structure, displays red luminescence at 599 and 649 nm. Remarkably, the reversible local protonation‐deprotonation behavior of the organic cations allows for exposure to polar solvents and heating to induce reversible structural and luminescent transformations between the two forms. Theoretical calculations reveal that the lower energy barrier associated with the deprotonation process within the pyrrole ring is responsible for the local protonation‐deprotonation behavior observed. These enantiomorphic hybrid zinc bromides also exhibit switchable circular dichroism (CD) and CPL properties. Furthermore, their chloride counterparts were successfully obtained by adjusting the halogen ions. Importantly, the unique stimuli‐responsive CPL characteristics position these hybrid zinc halides as promising candidates for applications in information storage, anti‐counterfeiting, and information encryption.
Long‐Life All‐Solid‐State Batteries Enabled by Cold‐Pressed Garnet Composite Electrolytes with Enhanced Li+ Conduction
Authors: Xiong Bing‐Qing , Zhang Jianwei , Nian Qingshun , Liu Xiaoye , Jiang Jinyu , Wang Zihong , Yang Zhenzhong , Ren Xiaodi
Published: August 2024

Garnet Li7La3Zr2O12 (LLZO)‐based solid‐state electrolytes (SSEs) hold promise for realizing next‐generation lithium metal batteries with high energy density. However, the high stiffness of high‐temperature sintered LLZO makes it brittle and susceptible to strain during the fabrication of solid‐state batteries. Cold‐pressed LLZO exhibits improved ductility but suffers from insufficient Li+ conductivity. Here, we report cold‐pressed Ta‐doped LLZO (Ta−LZ) particles integrated with ductile Li6PS5Cl (LPSC) via a Li+ conductive Li‐containing Ta−Cl structure. This configuration creates a continuous Li+ conduction network by enhancing the Li+ exchange at the Ta−LZ/LPSC interface. The resulting Ta−LZ/LPSC SSE exhibits Li+ conductivity of 4.42×10−4 S cm−1 and a low activation energy of 0.31 eV. Li symmetric cells with Ta−LZ/LPSC SSE demonstrate excellent Li dendrite suppression ability, with an improved critical current density of 5.0 mA cm−2 and a prolonged cycle life exceeding 600 h at 1 mA cm−2. Our finding provides valuable insights into developing cold‐pressed ceramic powder electrolytes for high‐performance all‐solid‐state batteries.
Nonplanar Nanographene: A Hydrocarbon Hole‐Transporting Material That Competes with Triarylamines
Authors: Morinaka Yuta , Ito Hideto , Fujimoto Kazuhiro J. , Yanai Takeshi , Ono Yohei , Tanaka Tsuyoshi , Itami Kenichiro
Published: August 2024

Hole‐transporting materials (HTMs) are essential for optoelectronic devices, such as organic light‐emitting diodes (OLEDs), dye‐sensitized solar cells, and perovskite solar cells. Triarylamines have been employed as HTMs since they were introduced in 1987. However, heteroatoms or side chains embedded in the core skeleton of triarylamines can cause thermal and chemical stability problems. Herein, we report that hexabenzo[a,c,fg,j,l,op]tetracene (HBT), a small nonplanar nanographene, functions as a hydrocarbon HTM with hole transport properties that match those of triarylamine‐based HTMs. X‐ray structural analysis and theoretical calculations revealed effective multidirectional orbital interactions and transfer integrals for HBT. In‐depth experimental and theoretical analyses revealed that the nonplanarity‐inducing annulative π‐extension can achieve not only a stable amorphous state in bulk films, but also a higher increase in the highest occupied molecular orbital level than conventional linear or cyclic π‐extension. Furthermore, an in‐house manufactured HBT‐based OLED exhibited excellent performance, featuring superior curves for current density–voltage, external quantum efficiency–luminance, and lifetime compared to those of representative triarylamine‐based OLEDs. A notable improvement in device lifetime was observed for the HBT‐based OLED, highlighting the advantages of the hydrocarbon HTM. This study demonstrates the immense potential of small nonplanar nanographenes for optoelectronic device applications.
Highly Potent and Intestine Specific P‐Glycoprotein Inhibitor to Enable Oral Delivery of Taxol
Authors: Zhou Xianjing , Zhang Ping , Yang Yuyan , Shi Wei , Liu Lei , Lai Zhencheng , Zhang Xing , Pan Peichen , Li Lan , Du Juan , Qian Hai , Cui Sunliang
Published: August 2024

Taxol is widely used in cancer chemotherapy; however, the oral absorption of Taxol remains a formidable challenge. Since the intestinal p‐glycoprotein (P‐gp) mediated drug efflux is one of the primary causes, the development of P‐gp inhibitor is emerging as a promising strategy to realize Taxol's oral delivery. Because P‐gp exists in many tissues, the non‐selective P‐gp inhibitors would lead to toxicity. Correspondingly, a potent and intestine specific P‐gp inhibitor would be an ideal solution to boost the oral absorption of Taxol and avoid exogenous toxicity. Herein, we would like to report a highly potent and intestine specific P‐gp inhibitor to enable oral delivery of Taxol in high efficiency. Through a multicomponent reaction and post‐modification, various benzofuran‐fused‐piperidine derivatives were achieved and the biological evaluation identified 16 c with potent P‐gp inhibitory activity. Notably, 16 c was intestine specific and showed almost none absorption (F=0.82 %), but possessing higher efficacy than Encequidar to improve the oral absorption of Taxol. In MDA‐MB‐231 xenograft model, the oral administration of Taxol and 16 c showed high therapeutic efficiency and low toxicity, thus providing a valuable chemotherapy strategy.
Dimethyl sulfoxide, an alternative for control of Nosema ceranae infection in honey bees (Apis mellifera)
Authors: Ho Shang‐Tse , Nai Yu‐Shin , Chang Zih‐Ting , Chang Ju‐Chun , Hsu Wei‐Chen , Ko Chung‐Yu , Chen Yue‐Wen , Yang Yu‐Liang
Published: August 2024

Nosema ceranae is a microsporidian parasite that threatens current apiculture. N. ceranae‐infected honey bees (Apis mellifera) exhibit morbid physiological impairments and reduced honey production, malnutrition, shorter life span, and higher mortality than healthy honey bees. In this study, we found that dimethyl sulfoxide (DMSO) could enhance the survival rate of N. ceranae‐infected honey bees. Therefore, we investigated the effect of DMSO on N. ceranae‐infected honey bees using comparative RNA sequencing analysis. Our results revealed that DMSO was able to affect several biochemical pathways, especially the metabolic‐related pathways in N. ceranae‐infected honey bees. Based on these findings, we conclude that DMSO may be a useful alternative for treating N. ceranae infection in apiculture.
MaxKinEff: A Collision Theory‐Based Approach for Analyzing Turnover Frequency and Turnover Number in Catalytic Processes
Authors: Bhattacharyya Himangshu Pratim , Sarma Manabendra
Published: August 2024

The efficiency of catalysts relies on comprehending the underlying kinetics that govern their performance. Under the steady‐state regime, the “rate” is referred to as the turnover frequency, where the reaction rate is first order with respect to catalysts. Here, we introduce the Maximum Kinetic Efficiency (MaxKinEff) model, grounded in collision theory, to predict efficiency based on maximum turnover frequency,
and maximum turnover number,
. The model was applied to molecular water oxidation using twenty‐six transition metal catalysts from the first (3d), second (4d), and third (5d) rows. A thorough investigation reveals that [Ru(pda)(Br‐py)2] (pda=1,10‐phenanthroline‐2,9‐dicarboxylate; Py=pyridinophane) exhibits a notable
of 1176.87×10−5 s−1 due to its larger collision diameter (σRC) and lower activation energy (Ea). Importantly, the trend in the computed
values aligns with experimental TON,
validating the model's accuracy. For instance, [Cp*Ir(κ2‐N,O)NO3] is identified by MaxKinEff as a standout performer, with the normalized maximum computed TON,
resembling the experimental TON,
=2000.
SuFEx‐Functionalized Quinones via Ruthenium‐Catalyzed C−H Alkenylation: A Potential Building Block for Bioactivity Valorization
Authors: de Oliveira Joyce C. , Abreu Breno U. , Paz Esther R. S. , Almeida Renata G. , Honorato João , Souza Cauê P. , Fantuzzi Felipe , Ramos Victor F. S. , Menna‐Barreto Rubem F. S. , Araujo Maria H. , Jardim Guilherme A. M. , da Silva Júnior Eufrânio N.
Published: August 2024

Herein, we describe the Ru‐catalyzed C−H alkenylation of 1,4‐naphthoquinones (1,4‐NQs), resulting in 1,4‐naphthoquinoidal/SuFEx hybrids with moderate to good yields. This method provides a novel route for direct access to ethenesulfonyl‐fluorinated quinone structures. We conducted mechanistic studies to gain an in‐depth understanding of the elementary steps of the reaction. Additionally, we evaluated the prototypes against trypomastigote forms of T. cruzi, leading to the identification of compounds with potent trypanocidal activity.
Pore‐Filling Induced Solid Electrolyte Failure of Ti‐Doped Na3Zr2Si2PO12 Characterized by Operando Synchrotron X‐Ray Tomography**
Authors: Li Mengya , Dixit Marm , Shevchenko Pavel , De Carlo Francesco , Balasubramanian Mahalingam , Belharouak Ilias
Published: August 2024

Solid‐state batteries (SSBs), particularly those utilizing sodium metal, are emerging as a promising technology due to their potential for enhanced safety, higher energy density, and longer cycle life. NASICON (Na superionic conductor) materials, known for their robust crystalline structure and high ionic conductivity, are pivotal in the development of efficient sodium all‐solid‐state batteries. These materials exhibit high room‐temperature ionic conductivity and electrochemical stability, making them ideal for various applications. Research has focused on improving NASICON's ionic conductivity and stability through doping, interface regulation, and composite anode design. Recent advancements include Ti‐doped Na3Zr2Si2PO12 (Ti‐NZSP), which demonstrates improved surface stability, higher ionic conductivity, and increased critical current density. However, challenges such as Na dendrite formation and mechanical integrity under operational conditions persist. Advanced imaging techniques like operando synchrotron X‐ray tomography have provided insights into failure mechanisms, revealing that pore‐filling and dendrite growth are significant issues. Understanding these processes is essential for enhancing the performance and safety of Na‐based SSBs. This study underscores the need for continued research to address these challenges and develop reliable, high‐performance solid‐state electrolytes for future energy storage solutions.
Lead brownfields and birth defects in North Carolina 2003–2015: A cross‐sectional case–control study
Authors: Slawsky Erik D. , Weaver Anne M. , Luben Thomas J. , Rappazzo Kristen M.
Published: August 2024

Background

Brownfields consist of abandoned and disused sites, spanning many former purposes. Brownfields represent a heterogenous yet ubiquitous exposure for many Americans, which may contain hazardous wastes and represent urban blight. Neonates and pregnant individuals are often sensitive to subtle environmental exposures. We evaluate if residential exposure to lead (Pb) brownfields is associated with birth defects.

Methods

Using North Carolina birth records from 2003 to 2015, we sampled 169,499 births within 10 km of a Pb brownfield with 3255 cardiovascular, central nervous, or external defects identified. Exposure was classified by binary specification of residing within 3 km of a Pb brownfield. We utilized multivariable logistic regression models adjusted for demographic covariates available from birth records and 2010 Census to estimate odds ratios (OR) and 95% confidence intervals (CI). Effect measure modification was assessed by inclusion of interaction terms and stratification for the potential modifiers of race/ethnicity and diabetes status.

Results

We observed positive associations between cardiovascular birth defects and residential proximity to Pb brownfields, OR (95%CI): 1.15 (1.04, 1.26), with suggestive positive associations for central nervous 1.16 (0.91, 1.47) and external defects 1.19 (0.88, 1.59). We did observe evidence of effect measure modification via likelihood ratio tests (LRT) for race/ethnicity for central nervous and external defect groups (LRT p values 0.08 and 0.02). We did observe modification by diabetes status for the cardiovascular group (LRT p value 0.08).

Conclusions

Our results from this analysis indicate that residential proximity to Pb brownfields is associated with cardiovascular birth defects with suggestive associations for central nervous and external defects. In‐depth analyses of individual defects and other contaminants or brownfield site functions may reveal additional novel associations.
The influence of apigenin on cellular responses to radiation: From protection to sensitization
Authors: Monadi Taha , Mohajer Zahra , Soltani Afsaneh , Khazeei Tabari Mohammad Amin , Manayi Azadeh , Azadbakht Mohammad
Published: August 2024

Apigenin, a dietary flavonoid, has gained increasing attention for its potential therapeutic applications in radiation protection and radiosensitization. Ionizing radiation (IR) can harm healthy cells, but as radiotherapy remains crucial in cancer treatment. Owing to the remarkable application of radiotherapy in the treatment of cancers, it is vital to protect healthy cells from radiation hazards while increasing the sensitivity of cancer cells to radiation. This article reviews the current understanding of apigenin's radioprotective and radiosensitive properties with a focuses on the involved signaling pathways and key molecular targets. When exposed to irradiation, apigenin reduces inflammation via cyclooxygenase‐2 inhibition and modulates proapoptotic and antiapoptotic biomarkers. Apigenin's radical scavenging abilities and antioxidant enhancement mitigate oxidative DNA damage. It inhibits radiation‐induced mammalian target of rapamycin activation, vascular endothelial growth factor (VEGF), matrix metalloproteinase‐2 (MMP), and STAT3 expression, while promoting AMPK, autophagy, and apoptosis, suggesting potential in cancer prevention. As a radiosensitizer, apigenin inhibits tumor growth by inducing apoptosis, suppressing VEGF‐C, tumor necrosis factor alpha, and STAT3, reducing MMP‐2/9 activity, and inhibiting cancer cell glucose uptake. Cellular and animal studies support apigenin's radioprotective and anticancer potential, making it a potential candidate for further research. Investigation into apigenin's therapeutic efficacy in diverse cancer types and radiation damage is essential.
“CARBGAME” (CARd & Board GAmes in Medical Education) as an innovative gamification tool for learning clinical enzymology in biochemistry for first year medical students
Authors: Surapaneni Krishna Mohan
Published: August 2024

Gamification is emerging as an active learning innovation in medical education to enhance student engagement and promote life‐long learning in a unique and collaborative environment. Clinical enzymology in biochemistry is one of the core topics in the medical curriculum. However, students face challenges in comprehension and retention of information. Hence, CARd & Board GAmes in Medical Education (CARBGAME) was introduced and evaluated for its effectiveness in enhancing learning, application, and retention of knowledge in clinical enzymology via gamification context. This mixed‐method study involved 150 first‐year undergraduate medical students. Before the game, students completed a pre‐test in clinical enzymology. Later they were divided into 25 small groups to compete in the board game designed for enzymology in biochemistry. The students took turns throwing the dice and answering the questions on the game board to continue moving forward. The first team to reach 100 and solve the case‐based question was deemed the winner. Following the board game, the students took up the post‐test to compare the educational impact of the innovation. Also, the subsequent internal assessment scores were compared with previous batch who were not implemented with this intervention. Then students evaluated the effectiveness of CARBGAME—Clinical Enzymology using a 32‐item questionnaire on 5‐point Likert scale. The feedback obtained on a 10‐point rating scale and for qualitative analysis, students' and faculty perceptions were recorded in small groups. CARBGAME received overwhelmingly positive feedback from both students and faculty. It was perceived well by students for being fun, relevant, consistent, motivating, collaborative, and promoting experiential learning. The game's low‐stakes approach, effective feedback, and sense of accomplishment were highly appreciated, making it a valuable tool for education. A significant improvement in knowledge was recorded, from a mean score of 8.37 ± 1.126 on a 20‐point scoring scale before the game to 16.53 ± 1.219 after with a p‐value of 0.0001. The comparison of the internal assessment scores between the intervention and non‐intervention group of students also showed a significant improvement among those implemented with CARBGAME (p < 0.0001). The CARBGAME innovation has achieved the intended outcome of promoting active learning and enhanced performance in clinical enzymology. Highly positive responses from faculty and students also indicate the exigent need to introduce innovative components like games into curricula to achieve student engagement and promote a meaningful learning experience.
MSMEs and economic growth: Fostering an entrepreneurial ecosystem in Bangladesh for sustainable development
Authors: Dhar Soma , Zaman Kazi Arif Uz , Dhar Bablu Kumar
Published: August 2024

Micro, small, and medium‐sized enterprises (MSMEs) are fundamental to the economy of Bangladesh, significantly contributing to job creation and poverty alleviation. Securing financing is essential for the growth and development of the MSME sector. This research investigates the entrepreneurial environment in Bangladesh, highlighting challenges and opportunities to enhance youth entrepreneurship. By analyzing secondary data from 2010 to 2022, the study employs a multiple regression model to examine the statistical relationship between MSME financing and economic growth. Gross domestic product Regression Equation Specification Error Test per capita is the dependent variable, loans to MSMEs are used as a proxy for MSME financing, and the unemployment rate is included as a control variable. The results indicate that MSME financing has a substantial positive impact on economic growth, while the unemployment rate has a significant negative effect. The study suggests implementing blended finance funds and a variety of supply, demand, and financial solutions to strengthen the MSME ecosystem in Bangladesh, thereby supporting national development goals and sustainable development.
Activated neutrophils: A next generation cellular immunotherapy
Authors: Kumbhojkar Ninad , Mitragotri Samir
Published: August 2024

Cell therapies are at the forefront of novel therapeutics. Neutrophils, despite being the most populous immune cells in human blood circulation, are not considered a viable option for cellular therapies because of their short lifespan and poor understanding of their role in the pathophysiology of various diseases. In inflammatory conditions, neutrophils exhibit an activated phenotype. Activation brings about significant changes to neutrophil biology such as increased lifespan, inflammatory cytokine secretion, and enhanced effector functions. Activated neutrophils also possess the potential to stimulate the downstream immune response and are described as essential effectors in the immune response to tumors. This makes activated neutrophils an interesting candidate for cell therapies. Here, we review the biology of activated neutrophils in detail. We discuss the different ways neutrophils can be activated and the effect they have on other immune cells for stimulation of downstream immune response. We review the conditions where activated neutrophil therapy can be therapeutically beneficial and discuss the challenges associated with their eventual translation. Overall, this review summarizes the current state of understanding of neutrophil‐based immunotherapies and their clinical potential.
Immunotherapy against glioblastoma using backpack‐activated neutrophils
Authors: Fukuta Tatsuya , Kumbhojkar Ninad , Prakash Supriya , Shaha Suyog , Silva‐Candal A. Da , Park Kyung Soo , Mitragotri Samir
Published: August 2024

Immune checkpoint inhibitors (ICIs) represent new therapeutic candidates against glioblastoma multiforme (GBM); however, their efficacy is clinically limited due to both local and systemic immunosuppressive environments. Hence, therapeutic approaches that stimulate local and systemic immune environments can improve the efficacy of ICIs. Here, we report an adoptive cell therapy employing neutrophils (NE) that are activated via surface attachment of drug‐free disk‐shaped backpacks, termed Cyto‐Adhesive Micro‐Patches (CAMPs) for treating GBM. CAMP‐adhered neutrophils (NE/CAMPs) significantly improved the efficacy of an anti‐PD1 antibody (aPD‐1) in a subcutaneous murine GBM model (GL261). A combination of NE/CAMPs and aPD‐1 completely regressed subcutaneous GL261 tumors in mice. The efficacy of NE/CAMPs against GBM was also tested in an orthotopic GL261 model. Neutrophil's ability to migrate into the brain was not affected by CAMP attachment, and intracerebral NE/CAMP accumulation was observed in mice‐bearing orthotopic GBM. The combination treatment of NE/CAMPs and aPD‐1 activated systemic immune responses mediated by T cells and showed improved therapeutic responses compared with aPD‐1 alone in the orthotopic GBM model. These results suggest that immunomodulation with NE/CAMPs offers a potential approach for the treatment of GBM by combination with ICIs.
Neoadjuvant chemoimmunotherapy was associated with better short‐term survival of patients with locally advanced esophageal squamous cell carcinoma compared to neoadjuvant chemoradiotherapy
Authors: Duan Xiaofeng , Zhao Fangdong , Shang Xiaobin , Yue Jie , Chen Chuangui , Ma Zhao , Chen Zuoyu , Zhang Chen , Pang Qingsong , Zhang Wencheng , Abbas Abbas E. , Jiang Hongjing
Published: August 2024

Introduction

The chemotherapy and immunotherapy combination is currently the primary strategy to treat metastatic esophageal squamous cell carcinoma (ESCC). Neoadjuvant chemoimmunotherapy (NCIT) is being intensively investigated for treating locally advanced ESCC.

Objective

We compared the efficacy and safety of NCIT and neoadjuvant chemoradiotherapy (NCRT) to treat locally advanced ESCC.

Methods

We included 214 locally advanced ESCC patients who were administered neoadjuvant therapy from May 2014 to April 2022. The patients were grouped according to two neoadjuvant protocols (NCIT and NCRT) routinely used at our institution. Perioperative findings, pathological results, and survival data were compared between the two groups by conducting unmatched and 1:1 propensity score matching (PSM) analyses.

Results

Following 1:1 PSM analysis of the confounders, 66 patients were allocated to each of the two groups. Time span between neoadjuvant therapy completion and esophagectomy was significantly longer after NCRT than that after NCIT (47.1 ± 13.2 days vs. 34.7 ± 8.8 days; p < 0.001). The NCIT group exhibited significantly greater number of harvested lymph nodes than the NCRT group (33.6 ± 12.7 vs. 21.7 ± 10.2; p < 0.001). The pathological complete response and major pathological response rates were similar between the two groups [NCIT group: 25.8% (17/66) and 62.1% (41/66), respectively; NCRT group: 27.3% (18/66) and 56.1% (37/66), respectively (p > 0.05)]. The overall incidence of pneumonia, anastomotic leakage, or postoperative complications did not differ significantly between the two groups. The 2‐year cumulative overall survival rates and the 2‐year disease‐free survival rates of the NCIT and NCRT groups were 80.2% and 62.2%, respectively (p = 0.029) and 70.0% and 50.8%, respectively (p = 0.023).

Conclusion

In locally advanced ESCC patients, short‐term survival after NCIT is superior to that after NCRT, with similar perioperative and pathological outcomes.
Initial ribociclib plus endocrine therapy for HR+/HER2− advanced breast cancer in pre‐ and postmenopausal Chinese women: Primary results from a phase 2 randomized study
Authors: Shao Zhimin , Tong Zhongsheng , Liu Qiang , Li Wei , Cai Li , Shen Kunwei , Li Huiping , Wang Chuan , Yang Jin , Song Zhenchuan , Wang Shui , Luo Ting , Zhao Wenhe , Wang Haibo , Pan Yueyin , Nie Jianyun , Zeng Xiaohua , Bai Yanqing , Chiang Wendy , Guarnaccia Valeria , Bi Yu , Xu Binghe
Published: August 2024

Background

The MONALEESA‐7 and ‐2 phase 3 randomized trials demonstrated a statistically significant progression‐free survival (PFS) and overall survival (OS) benefit with initial ribociclib + endocrine therapy (ET) versus placebo + ET in pre‐ and postmenopausal patients with hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC), respectively. Similar trends were observed in Asian subgroup analyses. This phase 2 bridging study of initial ET + ribociclib enrolled pre‐ and postmenopausal patients with HR+/HER2– ABC from China and was conducted to demonstrate consistency of PFS results in a Chinese population relative to the global MONALEESA‐7 and ‐2 studies.

Methods

Patients were randomized (1:1) to ET (nonsteroidal aromatase inhibitor + goserelin for premenopausal patients; letrozole for postmenopausal patients) + either ribociclib or placebo. The primary endpoint was investigator‐assessed PFS.

Results

As of April 25, 2022, the median follow‐up was 34.7 months in both cohorts. In the premenopausal cohort, median PFS was 27.6 months in the ribociclib arm (n = 79) versus 14.7 months in the placebo arm (n = 77) (hazard ratio 0.67 [95% CI: 0.45, 1.01]). In the postmenopausal cohort, median PFS was not reached in the ribociclib arm versus 18.5 months in the placebo arm (n = 77 in each arm) (hazard ratio 0.40 [95% CI: 0.26, 0.62]). Data also suggested improvements in secondary efficacy endpoints, although OS data were not mature. The safety profile in this population was consistent with that in global studies.

Conclusions

These data demonstrate a favorable benefit–risk profile for ribociclib + ET in Chinese patients.
Bioassay‐Guided Fractionation of Anti‐Leishmania Amazonensis Extracts from Ampelozizyphus Amazonicus by High‐Speed Countercurrent Chromatography
Authors: Mendonça Simony Carvalho , Rangel de Paula Leonardo , Soares Deivid Costa , do Nascimento Alan Menezes , Freire Campos Mariana , Gomes Brendo Araujo , da Fonseca Thamirys Silva , Simas Rosineide Costa , Saraiva Elvira Maria , Leitão Suzana Guimarães , Leitão Gilda Guimarães
Published: August 2024

Ampelozizyphus amazonicus Ducke, known as “saracura‐mirá” in the Amazon rainforest, is valued for its traditional use in malaria prevention and treatment. The plant's roots and bark are employed for these purposes, while the wood is often overlooked. Given the global importance of leishmaniasis, this research focused on A. amazonicus anti‐Leishmania amazonensis potential. The ethyl acetate extract from the bark (EAEB) exhibited the most effective inhibition of intracellular amastigote growth with IC50 7.0 μg mL−1 but showed high toxicity (CC50 9.0 μg mL−1). The wood ethanol (EW) and ethyl acetate (EAEW) extracts demonstrated promising results against L. amazonensis with IC50 15.8 μg mL−1 and 10.0 μg mL−1, CC50 50.5 μg mL−1 and 22.7 μg mL−1, respectively, with EW showing the greatest promise. High‐speed countercurrent chromatography (HSCCC) combined with mass spectrometry (MS) off‐line detection was employed for the bioassay‐guided fractionation of EAEB and EAEW using HEMWat as a solvent system. These extracts showed to be rich in saponins and triterpenes, besides the presence of glycosylated flavonoids recently reported as minor compounds. The fractions obtained from HSCCC showed high toxicity. However, this technique proved effective in obtaining fractions with a high purity level, leading to the identification of a di‐glycosylated triterpene saponin from EAEB, and melaleucic acid from EAEW. These findings highlight A. amazonicus as a potential source for developing new therapeutic alternatives for leishmaniasis and HSCCC as a technique enabling better separation efficiency of complex saponin matrices.
Novel Coumarin‐Steroid/Terpenoid Hybrids: In Vitro and In Silico Anticancer Studies
Authors: Martínez‐Lara Rosa I. , Cobos‐Ontiveros Luis A. , Meza‐Ireta Silvia A. , Martínez‐Montiel Mónica , Colín‐Lozano Blanca , Puerta Adrián , Padrón José M. , López Óscar , Vega‐Báez José Luis , Merino‐Montiel Penélope , Montiel‐Smith Sara
Published: August 2024

We have synthesized a series of novel coumarin‐steroid and triterpenoid hybrids and evaluated their potential anticancer activity through molecular docking calculations and in vitro antiproliferative assays. These hybrids, derived from estrone and oleanolic acid, were linked via hydrocarbon spacers of varying lengths. Molecular docking studies against human aromatase revealed strong interactions, particularly for compound 11d, which exhibited significant binding affinity (−12.6308 kcal/mol). In vitro assays demonstrated that compounds 6b and 11d had notable antiproliferative effects, with GI50 values of 5.4 and 7.0 μM against WiDr (colon) and HeLa (cervix) cancer cells, respectively. These findings highlight the potential of these hybrids as novel anticancer agents targeting aromatase, warranting further investigation and optimization.
Oral Administration of Kaempferol Isolated from Baccharis Mattogrosensis Enables In Vivo Activity Against Schistosoma Mansoni
Authors: Albuquerque Mara Marcia S. , Luz Rebecca Lustosa S. A. , Rodrigues Vinícius C. , Roquini Daniel B. , Umehara Eric , de Moraes Josué , Branco Alexsandro , Lago João Henrique G.
Published: August 2024

Baccharis mattogrosensis is a species from Asteraceae which has been used in Brazilian folk medicine to treatment of several illnesses, including those caused by parasites. In the present work, the MeOH extract of aerial parts of B. mattogrosensis was subjected to chromatographic fractionation to afford three flavonoids: apigenin (1), quercetin (2), and kaempferol (3) as well as a mixture three chlorogenic acids: 3,4‐O‐dicaffeoylquinic (4), 3,5‐O‐dicaffeoylquinic (5), and 4,5‐O‐dicaffeoylquinic (6) acids. When tested in vitro, kaempferol (3) exhibited activity against Schistosoma mansoni with EC50=81.86 μM, whereas compounds 1, 2, 4–6 showed to be inactives. Considering this result, the effects of kaempferol (3) against S. mansoni infection using an experimental approach (in vivo assay) was tested at first time. Using a single oral dose (400 mg/kg) of kaempferol (3) to S. mansoni‐infected mice reduced the worm burden by 25.5 %. Similarly, the number of eggs, which are responsible for a variety of pathologies and transmission of schistosomiasis, was decreased by 28.8 % in treated mice. Collectively, although kaempferol (3) is partially active when administered orally in a mouse model of schistosomiasis, our results suggest that this compound could be, in future studies, administered in different forms, such as nanoformulation.
Mycobolome of Phialomyces Macrosporus Across OSMAC‐Based Assorted Culture Media
Authors: de Jesus Vitória Evelyn Teles , Alvarenga Yasmin , Boffo Elisangela F. , Geris Regina
Published: August 2024

The fungus Phialomyces macrosporus was cultured using the One Strain Many Compounds (OSMAC) strategies to evaluate its metabolome. Variations in the nutrient culture media, culture regime, and cultivation parameters can significantly influence fungal extract quantity and chemical diversity. This study aimed to explore the mycobolome of P. macrosporus in five different culture media and two different cultivation conditions using NMR‐based metabolomics. Principal component analysis (PCA) of 1H‐NMR spectra revealed clear differentiation between these samples, highlighting the rice dextrose agar medium (RDA) and potato dextrose broth (PDB) as standard complex media for conducting a fungal metabolite screening program.