bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrapotent Broadly Neutralizing Human‐llama Bispecific Antibodies against HIV‐1
Authors: Xu Jianliang , Zhou Tongqing , McKee Krisha , Zhang Baoshan , Liu Cuiping , Nazzari Alexandra F. , Pegu Amarendra , Shen Chen‐Hsiang , Becker Jordan E. , Bender Michael F. , Chan Payton , Changela Anita , Chaudhary Ridhi , Chen Xuejun , Einav Tal , Kwon Young Do , Lin Bob C. , Louder Mark K. , Merriam Jonah S. , Morano Nicholas C. , O'Dell Sijy , Olia Adam S. , Rawi Reda , Roark Ryan S. , Stephens Tyler , Teng I‐Ting , Tourtellott‐Fogt Emily , Wang Shuishu , Yang Eun Sung , Shapiro Lawrence , Tsybovsky Yaroslav , Doria‐Rose Nicole A. , Casellas Rafael , Kwong Peter D.
Published: May 2024

Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV‐1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion‐stabilized HIV‐1 envelope (Env) trimer, BG505 DS‐SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4‐binding site (CD4bs) of vulnerability. Two of the vaccine‐elicited CD4bs‐targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a‐hinge region and human IgG1‐constant region (G36×3‐IgG2a and R27×3‐IgG2a), neutralized 96% of a multiclade 208‐strain panel at geometric mean IC80s of 0.314 and 0.033 µg mL−1, respectively. Cryo‐EM structures of these nanobodies in complex with Env trimer revealed the two nanobodies to neutralize HIV‐1 by mimicking the recognition of the CD4 receptor. To enhance their neutralizing potency and breadth, nanobodies are linked to the light chain of the V2‐apex‐targeting broadly neutralizing antibody, CAP256V2LS. The resultant human‐llama bispecific antibody CAP256L‐R27×3LS exhibited ultrapotent neutralization and breadth exceeding other published HIV‐1 broadly neutralizing antibodies, with pharmacokinetics determined in FcRn‐Fc mice similar to the parent CAP256V2LS. Vaccine‐elicited llama nanobodies, when combined with V2‐apex broadly neutralizing antibodies, may therefore be able to fulfill anti‐HIV‐1 therapeutic and prophylactic clinical goals.
Sex‐Specific Association Between Childhood Adversity and Accelerated Biological Aging
Authors: Yu Jie , Pu Fan , Yang Gan , Hao Meng , Zhang Hui , Zhang Jingyun , Cao Xingqi , Zhu Lijun , Wan Yuhui , Wang Xiaofeng , Liu Zuyun
Published: May 2024

Is childhood adversity associated with biological aging, and if so, does sex modify the association, and do lifestyle and mental health mediate the association? A lifespan analysis is conducted using data on 142 872 participants from the UK Biobank to address these questions. Childhood adversity is assessed through the online mental health questionnaire (2016), including physical neglect, physical abuse, emotional neglect, emotional abuse, sexual abuse, and a cumulative score. Biological aging is indicated by telomere length (TL) measured from leukocyte DNA using qPCR, and the shorter TL indicates accelerated biological aging; a lifestyle score is constructed using body mass index, physical activity, drinking, smoking, and diet; mental disorder is assessed using depression, anxiety, and insomnia at the baseline survey. The results reveal a sex‐specific association such that childhood adversity is associated with shorter TL in women after adjusting for covariates including polygenic risk score for TL, but not in men. Unhealthy lifestyle and mental disorder partially mediate the association in women. The proportions of indirect effects are largest for sexual and physical abuse. These findings highlight the importance of behavioral and psychological interventions in promoting healthy aging among women who experienced childhood adversity, particularly sexual and physical abuse.
Scanning Electron Microscopy Imaging of Large DNA Molecules Using a Metal‐Free Electro‐Stain Composed of DNA‐Binding Proteins and Synthetic Polymers
Authors: Noh Chanyoung , Kang Yoonjung , Heo Sujung , Kim Taesoo , Kim Hayeon , Chang Junhyuck , Sundharbaabu Priyannth Ramasami , Shim Sanghee , Lim Kwang‐il , Lee Jung Heon , Jo Kyubong
Published: May 2024

This paper presents the first scanning electron microscopy (SEM)‐based DNA imaging in biological samples. This novel approach incorporates a metal‐free electro‐stain reagent, formulated by combining DNA‐binding proteins and synthetic polymers to enhance the visibility of 2‐nm‐thick DNA under SEM. Notably, DNA molecules stain with proteins and polymers appear as dark lines under SEM. The resulting DNA images exhibit a thickness of 15.0±4.0 nm. As SEM is the primary platform, it integrates seamlessly with various chemically functionalized large surfaces with the aid of microfluidic devices. The approach allows high‐resolution imaging of various DNA structures including linear, circular, single‐stranded DNA and RNA, originating from nuclear and mitochondrial genomes. Furthermore, quantum dots are successfully visualized as bright labels that are sequence‐specifically incorporated into DNA molecules, which highlights the potential for SEM‐based optical DNA mapping. In conclusion, DNA imaging using SEM with the novel electro‐stain offers electron microscopic resolution with the ease of optical microscopy.
Mitochondria‐Targeted Nanoadjuvants Induced Multi‐Functional Immune‐Microenvironment Remodeling to Sensitize Tumor Radio‐Immunotherapy
Authors: Zhou Zaigang , Li Cheng , Li Chao , Zhou Lei , Tan Shuo , Hou Weibin , Xie Congying , Wang Long , Shen Jianliang , Xiong Wei
Published: May 2024

It is newly revealed that collagen works as a physical barrier to tumor immune infiltration, oxygen perfusion, and immune depressor in solid tumors. Meanwhile, after radiotherapy (RT), the programmed death ligand‐1 (PD‐L1) overexpression and transforming growth factor‐β (TGF‐β) excessive secretion would accelerate DNA damage repair and trigger T cell exclusion to limit RT efficacy. However, existing drugs or nanoparticles can hardly address these obstacles of highly effective RT simultaneously, effectively, and easily. In this study, it is revealed that inducing mitochondria dysfunction by using oxidative phosphorylation inhibitors like Lonidamine (LND) can serve as a highly effective multi‐immune pathway regulation strategy through PD‐L1, collagen, and TGF‐β co‐depression. Then, IR‐LND is prepared by combining the mitochondria‐targeted molecule IR‐68 with LND, which then is loaded with liposomes (Lip) to create IR‐LND@Lip nanoadjuvants. By doing this, IR‐LND@Lip more effectively sensitizes RT by generating more DNA damage and transforming cold tumors into hot ones through immune activation by PD‐L1, collagen, and TGF‐β co‐inhibition. In conclusion, the combined treatment of RT and IR‐LND@Lip ultimately almost completely suppressed the growth of bladder tumors and breast tumors.
HydrogelFinder: A Foundation Model for Efficient Self‐Assembling Peptide Discovery Guided by Non‐Peptidal Small Molecules
Authors: Ren Xuanbai , Wei Jiaying , Luo Xiaoli , Liu Yuansheng , Li Kenli , Zhang Qiang , Gao Xin , Yan Sizhe , Wu Xia , Jiang Xingyue , Liu Mingquan , Cao Dongsheng , Wei Leyi , Zeng Xiangxiang , Shi Junfeng
Published: May 2024

Self‐assembling peptides have numerous applications in medicine, food chemistry, and nanotechnology. However, their discovery has traditionally been serendipitous rather than driven by rational design. Here, HydrogelFinder, a foundation model is developed for the rational design of self‐assembling peptides from scratch. This model explores the self‐assembly properties by molecular structure, leveraging 1,377 self‐assembling non‐peptidal small molecules to navigate chemical space and improve structural diversity. Utilizing HydrogelFinder, 111 peptide candidates are generated and synthesized 17 peptides, subsequently experimentally validating the self‐assembly and biophysical characteristics of nine peptides ranging from 1–10 amino acids—all achieved within a 19‐day workflow. Notably, the two de novo‐designed self‐assembling peptides demonstrated low cytotoxicity and biocompatibility, as confirmed by live/dead assays. This work highlights the capacity of HydrogelFinder to diversify the design of self‐assembling peptides through non‐peptidal small molecules, offering a powerful toolkit and paradigm for future peptide discovery endeavors.
Electron Manipulation and Surface Reconstruction of Bimetallic Iron–Nickel Phosphide Nanotubes for Enhanced Alkaline Water Electrolysis
Authors: Wang Xinqiang , Zhou Jinhao , Cui Wengang , Gao Fan , Gao Yong , Qi Fulai , Liu Yanxia , Yang Xiaoying , Wang Ke , Li Zhenglong , Yang Yaxiong , Chen Jian , Sun Wenping , Sun Lixian , Pan Hongge
Published: May 2024

Developing high‐efficiency and stable bifunctional electrocatalysts for water splitting remains a great challenge. Herein, NiMoO4 nanowires as sacrificial templates to synthesize Mo‐doped NiFe Prussian blue analogs are employed, which can be easily phosphorized to Mo‐doped Fe2xNi2(1‐x)P nanotubes (Mo‐FeNiP NTs). This synthesis method enables the controlled etching of NiMoO4 nanowires that results in a unique hollow nanotube architecture. As a bifunctional catalyst, the Mo‐FeNiP NTs present lower overpotential and Tafel slope of 151.3 (232.6) mV at 100 mA cm−2 and 76.2 (64.7) mV dec−1 for HER (OER), respectively. Additionally, it only requires an ultralow cell voltage of 1.47 V to achieve 10 mA cm−2 for overall water splitting and can steadily operate for 200 h at 100 mA cm−2. First‐principles calculations demonstrate that Mo doping can effectively adjust the electron redistribution of the Ni hollow sites to optimize the hydrogen adsorption‐free energy for HER. Besides, in situ Raman characterization reveals the dissolving of doped Mo can promote a rapid surface reconstruction on Mo‐FeNiP NTs to dynamically stable (Fe)Ni‐oxyhydroxide layers, serving as the actual active species for OER. The work proposes a rational approach addressed by electron manipulation and surface reconstruction of bimetallic phosphides to regulate both the HER and OER activity.
High‐Performance Aluminum Fuels Induced by Monolayer Self‐Assembly of Nano‐Sized Energetic Fluoride Vesicles on the Surface
Authors: Wang Ruibin , Zhang Lichen , Li Xiaodong , Zhu Lixiang , Xiang Zilong , Xu Jin , Xue Dichang , Deng Zitong , Su Xing , Zou Meishuai
Published: May 2024

Surface modification is frequently used to solve the problems of low combustion properties and agglomeration for aluminum‐based fuels. However, due to the intrinsic incompatibility between the aluminum powder and the organic modifiers, the surface coating is usually uneven and disordered, which significantly deteriorates the uniformity and performances of the Al‐based fuels. Herein, a new approach of monolayer nano‐vesicular self‐assembly is proposed to prepare high‐performance Al fuels. Triblock copolymer G‐F‐G is produced by glycidyl azide polymer (GAP) and 2,2′‐(2,2,3,3,4,5,5‐Octafluorohexane‐1,6‐diyl) bis (oxirane) (fluoride) ring‐open addition reaction. By utilizing G‐F‐G vesicular self‐assembly in a special solvent, the nano‐sized vesicles are firmly adhered to the surface of Al powder through the long‐range attraction between the fluorine segments and Al. Meanwhile, the electrostatic repulsion between vesicles ensures an extremely thin coating thickness (≈15 nm), maintaining the monolayer coating structure. Nice ignition, combustion, anti‐agglomeration, and water‐proof properties of Al@G‐F‐G(DMF) are achieved, which are superior among the existing Al‐based fuels. The derived Al‐based fuel has excellent comprehensive properties, which can not only inspire the development of new‐generation energetic materials but also provide facile but exquisite strategies for exquisite surface nanostructure construction via ordered self‐assembly for many other applications.
Stepwise Toward Pure Blue Organic Light‐Emitting Diodes by Synergetically Locking and Shielding Carbonyl/Nitrogen‐Based MR‐TADF Emitters
Authors: Yu Jie‐Rong , Tan Hong‐Ji , Gao Xiu‐Qi , Wang Bing , Long Zhi‐Qiang , Liu Jia‐Li , Lin Zhi‐Zhong , Li Xing‐Yi , Zhu Ze‐Lin , Jian Jing‐Xin , Tong Qing‐Xiao , Lee Chun‐Sing
Published: May 2024

Deep‐blue multi‐resonance (MR) emitters with stable and narrow full‐width‐at‐half‐maximum (FWHM) are of great importance for widening the color gamut of organic light‐emitting diodes (OLEDs). However, most planar MR emitters are vulnerable to intermolecular interactions from both the host and guest, causing spectral broadening and exciton quenching in thin films. Their emission in the solid state is environmentally sensitive, and the color purity is often inferior to that in solutions. Herein, a molecular design strategy is presented that simultaneously narrows the FWHM and suppresses intermolecular interactions by combining intramolecular locking and peripheral shielding within a carbonyl/nitrogen‐based MR core. Intramolecularly locking carbonyl/nitrogen‐based bears narrower emission of 2,10‐dimethyl‐12,12‐diphenyl‐4H‐benzo[9,1]quinolizino[3,4,5,6,7‐defg]acridine‐4,8(12H)‐dione in solution and further with peripheral‐shielding groups, deep‐blue emitter (12,12‐diphenyl‐2,10‐bis(9‐phenyl‐9H‐fluoren‐9‐yl)−4H‐benzo[9,1]quinolizino[3,4,5,6,7‐defg]acridine‐4,8(12H)‐dione, DPQAO‐F) exhibits ultra‐pure emission with narrow FWHM (c.a., 24 nm) with minimal variations (∆FWHM ≤ 3 nm) from solution to thin films over a wide doping range. An OLED based on DPQAO‐F presents a maximum external quantum efficiency (EQEmax) of 19.9% and color index of (0.134, 0.118). Furthermore, the hyper‐device of DPQAO‐F exhibits a record‐high EQEmax of 32.7% in the deep‐blue region, representing the first example of carbonyl/nitrogen‐based OLED that can concurrently achieve narrow bandwidth in the deep‐blue region and a high electroluminescent efficiency surpassing 30%.
Self‐Powered Autonomous Electrostatic Dust Removal for Solar Panels by an Electret Generator
Authors: Ding Rong , Cao Zeyuan , Teng Junchi , Cao Yujia , Qian Xiaoyu , Yue Wei , Yuan Xiangzhu , Deng Kang , Wu Zibo , Li Shuiqing , Lin Liwei , Ye Xiongying
Published: May 2024

Solar panels often suffer from dust accumulation, significantly reducing their output, especially in desert regions where many of the world's largest solar plants are located. Here, an autonomous dust removal system for solar panels, powered by a wind‐driven rotary electret generator is proposed. The generator applies a high voltage between one solar panel's output electrode and an upper mesh electrode to generate a strong electrostatic field. It is discovered that dust particles on the insulative glass cover of the panel can be charged under the high electrical field, assisted by adsorbed water, even in low‐humidity environments. The charged particles are subsequently repelled from the solar panel with the significant Coulomb force. Two panels covered with sand dust are cleaned in only 6.6 min by a 15 cm diameter rotary electret generator at 1.6 m s−1wind speed. Experimental results manifest that the system can work effectively in a wide range of environmental conditions, and doesn't impact the panel performance for long‐term operation. This autonomous system, with its high dust removal efficiency, simplicity, and low cost, holds great potential in practical applications.
The Long Non‐Coding RNA Obesity‐Related (Obr) Contributes To Lipid Metabolism Through Epigenetic Regulation
Authors: Kaimala Suneesh , Lootah Shareena Saeed , Mehra Neha , Kumar Challagandla Anil , Marzooqi Saeeda Al , Sampath Prabha , Ansari Suraiya Anjum , Emerald Bright Starling
Published: May 2024

Obesity is a multifactorial disease that is part of today's epidemic and also increases the risk of other metabolic diseases. Long noncoding RNAs (lncRNAs) provide one tier of regulatory mechanisms to maintain metabolic homeostasis. Although lncRNAs are a significant constituent of the mammalian genome, studies aimed at their metabolic significance, including obesity, are only beginning to be addressed. Here, a developmentally regulated lncRNA, termed as obesity related (Obr), whose expression in metabolically relevant tissues such as skeletal muscle, liver, and pancreas is altered in diet‐induced obesity, is identified. The Clone 9 cell line and high‐fat diet‐induced obese Wistar rats are used as a model system to verify the function of Obr. By using stable expression and antisense oligonucleotide‐mediated downregulation of the expression of Obr followed by different molecular biology experiments, its role in lipid metabolism is verified. It is shown that Obr associates with the cAMP response element‐binding protein (Creb) and activates different transcription factors involved in lipid metabolism. Its association with the Creb histone acetyltransferase complex, which includes the cAMP response element‐binding protein (CBP) and p300, positively regulates the transcription of genes involved in lipid metabolism. In addition, Obr is regulated by Pparγ in response to lipid accumulation.
Multi‐Level Switching of Spin‐Torque Ferromagnetic Resonance in 2D Magnetite
Authors: Jia Zhiyan , Chen Qian , Wang Wenjie , Sun Rong , Li Zichao , Hübner René , Zhou Shengqiang , Cai Miming , Lv Weiming , Yu Zhipeng , Zhang Fang , Zhao Mengfan , Tian Sen , Liu Lixuan , Zeng Zhongming , Jiang Yong , Wang Zhongchang
Published: May 2024

2D magnetic materials hold substantial promise in information storage and neuromorphic device applications. However, achieving a 2D material with high Curie temperature (TC), environmental stability, and multi‐level magnetic states remains a challenge. This is particularly relevant for spintronic devices, which require multi‐level resistance states to enhance memory density and fulfil low power consumption and multi‐functionality. Here, the synthesis of 2D non‐layered triangular and hexagonal magnetite (Fe3O4) nanosheets are proposed with high TC and environmental stability, and demonstrate that the ultrathin triangular nanosheets show broad antiphase boundaries (bAPBs) and sharp antiphase boundaries (sAPBs), which induce multiple spin precession modes and multi‐level resistance. Conversely, the hexagonal nanosheets display slip bands with sAPBs associated with pinning effects, resulting in magnetic‐field‐driven spin texture reversal reminiscent of “0” and “1” switching signals. In support of the micromagnetic simulation, direct explanation is offer to the variation in multi‐level resistance under a microwave field, which is ascribed to the multi‐spin texture magnetization structure and the randomly distributed APBs within the material. These novel 2D magnetite nanosheets with unique spin textures and spin dynamics provide an exciting platform for constructing real multi‐level storage devices catering to emerging information storage and neuromorphic computing requirements.
Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity
Authors: Zhou Ying , Xue Rui , Li Yifei , Ran Wang , Chen Yuping , Luo Zhongyu , Zhang Kemeng , Zhang Ruoxia , Wang Junjun , Fang Mengmeng , Chen Cong , Lou Min
Published: May 2024

White matter hyperintensity (WMH) represents a critical global medical concern linked to cognitive decline and dementia, yet its underlying mechanisms remain poorly understood. Here, humans are directly demonstrated that high WMH burden correlates with delayed drainage of meningeal lymphatic vessels (mLVs) and glymphatic pathway. Additionally, a longitudinal cohort study reveals that glymphatic dysfunction predicts WMH progression. Next, in a rat model of WMH, the presence of impaired lymphangiogenesis and glymphatic drainage is confirmed, followed by elevated microglial activation and white matter demyelination. Notably, enhancing meningeal lymphangiogenesis through adeno‐associated virus delivery of vascular endothelial growth factor‐C (VEGF‐C) mitigates microglial gliosis and white matter demyelination. Conversely, blocking the growth of mLVs with a VEGF‐C trap strategy exacerbates these changes. The findings highlight the role of mLVs and glymphatic pathway dysfunction in aggravating brain white matter injury, providing a potential novel strategy for WMH prevention and treatment.
Bioinspired Robust Gas‐Permeable On‐Skin Electronics: Armor‐Designed Nanoporous Flash Graphene Assembly Enhancing Mechanical Resilience
Authors: Chen Yang , Liu Zixuan , Wang Zhigang , Yi Ying , Yan Chunjie , Xu Wenxia , Zhou Feng , Gao Yuting , Zhou Qitao , Zhang Cheng , Deng Heng
Published: May 2024

Soft on‐skin electrodes play an important role in wearable technologies, requiring attributes such as wearing comfort, high conductivity, and gas permeability. However, conventional fabrication methods often compromise simplicity, cost‐effectiveness, or mechanical resilience. In this study, a mechanically robust and gas‐permeable on‐skin electrode is presented that incorporates Flash Graphene (FG) integrated with a bioinspired armor design. FG, synthesized through Flash Joule Heating process, offers a small‐sized and turbostratic arrangement that is ideal for the assembly of a conductive network with nanopore structures. Screen‐printing is used to embed the FG assembly into the framework of polypropylene melt‐blown nonwoven fabrics (PPMF), forming a soft on‐skin electrode with low sheet resistance (125.2 ± 4.7 Ω/□) and high gas permeability (≈10.08 mg cm⁻2 h⁻¹). The “armor” framework ensures enduring mechanical stability through adhesion, washability, and 10,000 cycles of mechanical contact friction tests. Demonstrating capabilities in electrocardiogram (ECG) and electromyogram (EMG) monitoring, along with serving as a self‐powered triboelectric sensor, the FG/PPMF electrode holds promise for scalable, high‐performance flexible sensing applications, thereby enriching the landscape of integrated wearable technologies.
A Novel Nanozyme to Enhance Radiotherapy Effects by Lactic Acid Scavenging, ROS Generation, and Hypoxia Mitigation
Authors: Yao Yiran , Xu Ru , Shao Weihuan , Tan Ji , Wang Shaoyun , Chen Shuhan , Zhuang Ai , Liu Xuanyong , Jia Renbing
Published: May 2024

Uveal melanoma (UM) is a leading intraocular malignancy with a high 5‐year mortality rate, and radiotherapy is the primary approach for UM treatment. However, the elevated lactic acid, deficiency in ROS, and hypoxic tumor microenvironment have severely reduced the radiotherapy outcomes. Hence, this study devised a novel CoMnFe‐layered double oxides (LDO) nanosheet with multienzyme activities for UM radiotherapy enhancement. On one hand, LDO nanozyme can catalyze hydrogen peroxide (H2O2) in the tumor microenvironment into oxygen and reactive oxygen species (ROS), significantly boosting ROS production during radiotherapy. Simultaneously, LDO efficiently scavenged lactic acid, thereby impeding the DNA and protein repair in tumor cells to synergistically enhance the effect of radiotherapy. Moreover, density functional theory (DFT) calculations decoded the transformation pathway from lactic to pyruvic acid, elucidating a previously unexplored facet of nanozyme activity. The introduction of this innovative nanomaterial paves the way for a novel, targeted, and highly effective therapeutic approach, offering new avenues for the management of UM and other cancer types.
Tumor Microenvironment‐Responsive Nanocapsule Delivery CRISPR/Cas9 to Reprogram the Immunosuppressive Microenvironment in Hepatoma Carcinoma
Authors: He Lei , Li Zhaozhao , Su Danjie , Du Haichen , Zhang Kuo , Zhang Wangqian , Wang Shuning , Xie Fei , Qiu Yueyuan , Ma Shuangxin , Shi Gege , Yu Duo , Lei Xiaoying , Li Weina , Li Meng , Wang Zhaowei , Gu Jintao , Zhang Yingqi
Published: May 2024

Cancer immunotherapy has demonstrated significant efficacy in various tumors, but its effectiveness in treating Hepatocellular Carcinoma (HCC) remains limited. Therefore, there is an urgent need to identify a new immunotherapy target and develop corresponding intervention strategies. Bioinformatics analysis has revealed that growth differentiation factor 15 (GDF15) is highly expressed in HCC and is closely related to poor prognosis of HCC patients. The previous study revealed that GDF15 can promote immunosuppression in the tumor microenvironment. Therefore, knocking out GDF15 through gene editing could potentially reverse the suppressive tumor immune microenvironment permanently. To deliver the CRISPR/Cas9 system specifically to HCC, nanocapsules (SNC) coated with HCC targeting peptides (SP94) on their surface is utilized. These nanocapsules incorporate disulfide bonds (SNCSS) that release their contents in the tumor microenvironment characterized by high levels of glutathione (GSH). In vivo, the SNCSS target HCC cells, exert a marked inhibitory effect on HCC progression, and promote HCC immunotherapy. Mechanistically, CyTOF analysis showed favorable changes in the immune microenvironment of HCC, immunocytes with killer function increased and immunocytes with inhibitive function decreased. These findings highlight the potential of the CRISPR‐Cas9 gene editing system in modulating the immune microenvironment and improving the effectiveness of existing immunotherapy approaches for HCC.
De‐nitrosylation Coordinates Appressorium Function for Infection of the Rice Blast Fungus
Authors: Hu Hong , He Wenhui , Qu Zhiguang , Dong Xiang , Ren Zhiyong , Qin Mengyuan , Liu Hao , Zheng Lu , Huang Junbin , Chen Xiao‐Lin
Published: May 2024

As a signaling molecule, nitric oxide (NO) regulates the development and stress response in different organisms. The major biological activity of NO is protein S‐nitrosylation, whose function in fungi remains largely unclear. Here, it is found in the rice blast fungus Magnaporthe oryzae, de‐nitrosylation process is essential for functional appressorium formation during infection. Nitrosative stress caused by excessive accumulation of NO is harmful for fungal infection. While the S‐nitrosoglutathione reductase GSNOR‐mediated de‐nitrosylation removes excess NO toxicity during appressorium formation to promote infection. Through an indoTMT switch labeling proteomics technique, 741 S‐nitrosylation sites in 483 proteins are identified. Key appressorial proteins, such as Mgb1, MagB, Sps1, Cdc42, and septins, are activated by GSNOR through de‐nitrosylation. Removing S‐nitrosylation sites of above proteins is essential for proper protein structure and appressorial function. Therefore, GSNOR‐mediated de‐nitrosylation is an essential regulator for appressorium formation. It is also shown that breaking NO homeostasis by NO donors, NO scavengers, as well as chemical inhibitor of GSNOR, shall be effective methods for fungal disease control.
Why are triploid quaking aspen (Populus tremuloides) common?
Authors: Blonder Benjamin Wong
Published: May 2024

Premise

Quaking aspen is a clonal tree species that has mixed ploidy, often with high relative abundance of both diploids and triploids but no haploids or tetraploids. Triploids typically have low fertility, leaving their occurrence apparently unlikely from an evolutionary perspective, unless they provide a “triploid bridge” to generating higher‐fitness tetraploids—which are not observed in this species. This study focused on how triploidy can be maintained in quaking aspen.

Methods

A computational model was used to simulate gamete production, sexual reproduction, asexual reproduction, parent survival, and offspring survival in a population. All parameters were assumed to be cytotype‐dependent and environment‐independent. Sampling methods were used to identify parameter combinations consistent with observed cytotype frequencies.

Results

Many processes and parameter values were sufficient to yield a moderate frequency of triploids, and very few were necessary. The most plausible route involved higher triploid survival at the parent or offspring stage and limited unreduced gamete production by either diploid or triploid parents. Triploid fertility was helpful but not necessary.

Conclusions

The coexistence of diploids and triploids in quaking aspen is statistically likely and promoted by the existence of commonly observed, long‐lived triploid clones. However, other mechanisms not captured by the model related to environmental variation could also occur. Further empirical data or more complex but difficult‐to‐parameterize models are needed to gain further insight.
Low exposition to lithium prevents nephrogenic diabetes insipidus but not microcystic dilations of the collecting ducts in long‐term rat model
Authors: Tabibzadeh Nahid , Klein Mathieu , Try Mélanie , Poupon Joël , Houillier Pascal , Klein Christophe , Cheval Lydie , Crambert Gilles , Lasaad Samia , Chevillard Lucie , Megarbane Bruno
Published: May 2024

Lithium induces nephrogenic diabetes insipidus (NDI) and microcystic chronic kidney disease (CKD). As previous clinical studies suggest that NDI is dose‐dependent and CKD is time‐dependent, we investigated the effect of low exposition to lithium in a long‐term experimental rat model. Rats were fed with a normal diet (control group), with the addition of lithium (Li+ group), or with lithium and amiloride (Li+/Ami group) for 6 months, allowing obtaining low plasma lithium concentrations (0.25 ± 0.06 and 0.43 ± 0.16 mmol/L, respectively). Exposition to low concentrations of plasma lithium levels prevented NDI but not microcystic dilations of kidney tubules, which were identified as collecting ducts (CDs) on immunofluorescent staining. Both hypertrophy, characterized by an increase in the ratio of nuclei per tubular area, and microcystic dilations were observed. The ratio between principal cells and intercalated cells was higher in microcystic than in hypertrophied tubules. There was no correlation between AQP2 messenger RNA levels and cellular remodeling of the CD. Additional amiloride treatment in the Li+/Ami group did not allow consistent morphometric and cellular composition changes compared to the Li+ group. Low exposition to lithium prevented overt NDI but not microcystic dilations of the CD, with differential cellular composition in hypertrophied and microcystic CDs, suggesting different underlying cellular mechanisms.
The productivity paradox in carbon‐intensive companies: How eco‐innovation affects corporate environmental and financial performance
Authors: Czerny Albert , Letmathe Peter
Published: May 2024

Empirical studies analyzing the relationship between strategies to reduce greenhouse gas (GHG) emissions and firms' environmental and financial performance often fail to find significant effects when firms invest in innovative green technologies. Indeed, as efficiency and productivity gains of new technologies can often be reaped only after a certain time gap, cross‐sectional studies are bound to ignore the time component, thus becoming subject to the productivity paradox. Employing an integrative approach, drawing on eco‐efficiency theory, productivity paradox, and innovation diffusion principles, this longitudinal study observes companies with high GHG emissions during and after the first two European Union Emission Trading Scheme (EU ETS) trading periods (2005–2019). It analyzes (1) the dynamics of carbon reduction practices over time, (2) the impact of GHG reduction strategies on environmental performance, (3) the positive effect of GHG‐related efficiency improvements on firm performance, while considering (4) the moderating effect of GHG emissions type on the latter relationship.
Using Response Surface Methodology Approach to Modeling and Optimization of the Combustion Process in Cement Kiln
Authors: Mansouri Somayeh , Shahraki Farhad , Sadeghi Jafar , Sardashti Birjandi Mohammad Reza , Koohestanian Esmaeil
Published: May 2024

In this study, this process has been modeled and optimized using the design of experiment technique and response surface methodology (RSM). The RSM was employed to optimize the combustion process in the cement kiln. Kiln feed (X1 = 160–190 t h−1), fan speed (X2 = 840–870 rpm), kiln rotational speed (X3 = 2.8–3.4 rpm), kiln fuel rate (X4 = 3800–4150 L h−1), calciner fuel rate (X5 = 5700–6200 L h−1), pressure of kiln inlet (X6 = 98–102 Pa), and limestone saturation factor (LSF) (X7 = 94–95.8 %) as independent variables were investigated. The carbon monoxide and the kiln body temperature in RSM were considered as response variables. The absolute average error in the model predictions for the combustion process in the cement kiln, for the kiln body's temperature, is about 1.6 % and for carbon monoxide is about 15.5 %.
Design, synthesis, and bioactivity evaluation of clindamycin derivatives against multidrug‐resistant bacterial strains
Authors: Jia Yiduo , Zhang Yinmeng , Zhu Hong , Wang Ming
Published: May 2024

Our research aims to reduce the bacterial resistance of clindamycin against Gram‐positive bacteria and expand its range of bacterial susceptibility. First, we optimized the structure of clindamycin based on its structure–activity relationship. Second, we employed the fractional inhibitory concentration method to detect drugs suitable for combination with clindamycin derivatives. We then used a linker to connect the clindamycin derivatives with the identified combined therapy drugs. Finally, we tested antibacterial susceptibility testing and conducted in vitro bacterial inhibition activity assays to determine the compounds. with the highest efficacy. The results of our study show that we synthesized clindamycin propionate derivatives and clindamycin homo/heterodimer derivatives, which exhibited superior antibacterial activity compared to clindamycin and other antibiotics against both bacteria and fungi. In vitro bacteriostatic activity testing against four types of Gram‐negative bacteria and one type of fungi revealed that all synthesized compounds had bacteriostatic effects at least 1000 times better than clindamycin and sulfonamides. The minimum inhibitory concentration (MIC) values for these compounds ranged from 0.25 to 0.0325 mM. Significantly, compound 5a demonstrated the most potent inhibitory activity against three distinct bacterial strains, displaying MIC values spanning from 0.0625 to 0.0325 mM. Furthermore, our calculations indicate that compound 5a is safe for cellular use. In conclusion, the synthesized compounds hold great promise in addressing bacterial antibiotic resistance.
Noscapine modulates hypoxia‐induced angiogenesis and hemodynamics: Insights from a zebrafish model investigation
Authors: Nathan Jhansi , Shameera Rabiathul , Sivakumar Kaniha , Rajendran Soundarya , Perumal Elumalai
Published: May 2024

We investigated the angiogenesis‐modulating ability of noscapine in vitro using osteosarcoma cell line (MG‐63) and in vivo using a zebrafish model. MTT assay and the scratch wound healing assay were performed on the osteosarcoma cell line (MG‐63) to analyze the cytotoxic effect and antimigrative ability of noscapine, respectively. We also observed the antiangiogenic ability of noscapine on zebrafish embryos by analyzing the blood vessels namely the dorsal aorta, and intersegmental vessels development at 24, 48, and 72 h postfertilization. Real‐time polymerase chain reaction was used to analyze the hypoxia signaling molecules' gene expression in MG‐63 cells and zebrafish embryos. The findings from the scratch wound healing demonstrated that noscapine stopped MG‐63 cancer cells from migrating under both hypoxia and normoxia. Blood vessel development and the heart rate in zebrafish embryos were significantly reduced by noscapine under both hypoxia and normoxia which showed the hemodynamics impact of noscapine. Noscapine also downregulated the cobalt chloride (CoCl2) induced hypoxic signaling molecules' gene expression in MG‐63 cells and zebrafish embryos. Therefore, noscapine may prevent MG‐63 cancer cells from proliferating and migrating, as well as decrease the formation of new vessels and the production of growth factors linked to angiogenesis in vivo under both normoxic and hypoxic conditions.
Smell throughout the life course
Authors: Poirier Alice C. , Melin Amanda D.
Published: May 2024

The sense of smell is an important mediator of health and sociality at all stages of life, yet it has received limited attention in our lineage. Olfaction starts in utero and participates in the establishment of social bonds in children, and of romantic and sexual relationships after puberty. Smell further plays a key role in food assessment and danger avoidance; in modern societies, it also guides our consumer behavior. Sensory abilities typically decrease with age and can be impacted by diseases, with repercussions on health and well‐being. Here, we critically review our current understanding of human olfactory communication to refute outdated notions that our sense of smell is of low importance. We provide a summary of the biology of olfaction, give a prospective overview of the importance of the sense of smell throughout the life course, and conclude with an outline of the limitations and future directions in this field.
In vitro toxicity evaluation in A549 cells of diesel particulate matter from two different particle sampling systems and several resuspension media
Authors: Uski Oskari J. , Rankin Gregory D. , Wingfors Håkan , Magnusson Roger , Boman Christoffer , Muala Ala , Blomberg Anders , Bosson Jenny , Sandström Thomas
Published: May 2024

In urban areas, inhalation of fine particles from combustion sources such as diesel engines causes adverse health effects. For toxicity testing, a substantial amount of particulate matter (PM) is needed. Conventional sampling involves collection of PM onto substrates by filtration or inertial impaction. A major drawback to those methodologies is that the extraction process can modify the collected particles and alter their chemical composition. Moreover, prior to toxicity testing, PM samples need to be resuspended, which can alter the PM sample even further. Lastly, the choice of the resuspension medium may also impact the detected toxicological responses. In this study, we compared the toxicity profile of PM obtained from two alternative sampling systems, using in vitro toxicity assays. One system makes use of condensational growth before collection in water in an impinger – BioSampler (CG‐BioSampler), and the other, a Dekati® Gravimetric Impactor (DGI), is based on inertial impaction. In addition, various methods for resuspension of DGI collected PM were compared. Tested endpoints included cytotoxicity, formation of cellular reactive oxygen species, and genotoxicity. The alternative collection and suspension methods affected different toxicological endpoints. The water/dimethyl sulfoxide mixture and cell culture medium resuspended particles, along with the CG‐BioSampler sample, produced the strongest responses. The water resuspended sample from the DGI appeared least toxic. CG‐BioSampler collected PM caused a clear increased response in apoptotic cell death. We conclude that the CG‐BioSampler PM sampler is a promising alternative to inertial impaction sampling.
Downregulation of lncRNA MIR17HG reduced tumorigenicity and Treg‐mediated immune escape of non‐small‐cell lung cancer cells through targeting the miR‐17‐5p/RUNX3 axis
Authors: Zheng Guanghua , Ye Hui , Bai Junjun , Zhang Xia
Published: May 2024

Long noncoding RNA MIR17HG was involved with the progression of non‐small‐cell lung cancer (NSCLC), but specific mechanisms of MIR17HG‐mediated immune escape of NSCLC cells were still unknown. The present study investigated the function of MIR17HG on regulatory T cell (Treg)‐mediated immune escape and the underlying mechanisms in NSCLC. Expression of MIR17HG and miR‐17‐5p in NSCLC tissue samples were detected using quantitative real‐time PCR (qRT‐PCR). A549 and H1299 cells were transfected with sh‐MIR17HG, miR‐17‐5p inhibitor, or sh‐MIR17HG + miR‐17‐5p inhibitor, followed by cocultured with Tregs. Cell proliferation was measured using 5‐ethynyl‐20‐deoxyuridine (Edu) staining assay and cell counting kit‐8 (CCK‐8) assay. Flow cytometry was used for determining positive numbers of FOXP3+CD4+/CD25+/CD8+ Tregs. Through subcutaneous injection with transfected A549 cells, a xenograft nude mouse model was established. Weights and volumes of xenograft tumors were evaluated. Additionally, the expressions of immune‐related factors including transforming growth factor beta (TGF‐β), vascular endothelial growth factor A (VEGF‐A), interleukin‐10 (IL‐10), IL‐4, and interferon‐gamma (IFN‐γ) in cultured cells, were evaluated by enzyme‐linked immunosorbent assay and western blot analysis. Then, miR‐17‐5p was decreased and MIR17HG was enhanced in both NSCLC tissues and cell lines. MIR17HG knockdown significantly suppressed cell proliferation, tumorigenicity, and immune capacity of Tregs in A549 and H1299 cells, whereas sh‐MIR17HG significantly reduced expression levels of VEGF‐A, TGF‐β, IL‐4, and IL‐10 but promoted the IFN‐γ level in vitro and in vivo. Moreover, downregulation of miR‐17‐5p significantly reversed the effects of sh‐MIR17HG. Additionally, we identified that runt‐ related transcription factor 3 (RUNX3) was a target of miR‐17‐5p, and sh‐MIR17HG and miR‐17‐5p mimics downregulated RUNX3 expression. In conclusion, downregulation of MIR17HG suppresses tumorigenicity and Treg‐mediated immune escape in NSCLC through downregulating the miR‐17‐5p/RUNX3 axis, indicating that this axis contains potential biomarkers for NSCLC.
Concurrent inhibition of IR, ITGB1, and CD36 perturbated the interconnected network of energy metabolism and epithelial‐to‐mesenchymal transition in breast cancer cells
Authors: Kandasamy Thirukumaran , Sarkar Shilpi , Sen Plaboni , Venkatesh Dheepika , Ghosh Siddhartha Sankar
Published: May 2024

Altered energy metabolism is an emerging hallmark of cancer and plays a pivotal in cell survival, proliferation, and biosynthesis. In a rapidly proliferating cancer, energy metabolism acts in synergism with epithelial‐to‐mesenchymal transition (EMT), enabling cancer stemness, dissemination, and metastasis. In this study, an interconnected functional network governing energy metabolism and EMT signaling pathways was targeted through the concurrent inhibition of IR, ITGB1, and CD36 activity. A novel multicomponent MD simulation approach was employed to portray the simultaneous inhibition of IR, ITGB1, and CD36 by a 2:1 combination of Pimozide and Ponatinib. Further, in‐vitro studies revealed the synergistic anticancer efficacy of drugs against monolayer as well as tumor spheroids of breast cancer cell lines (MCF‐7 and MDA‐MB‐231). In addition, the combination therapy exerted approximately 40% of the apoptotic population and more than 1.5‐ to 3‐fold reduction in the expression of ITGB1, IR, p‐IR, IRS‐1, and p‐AKT in MCF‐7 and MDA‐MB‐231 cell lines. Moreover, the reduction in fatty acid uptake, lipid droplet accumulation, cancer stemness, and migration properties were also observed. Thus, targeting IR, ITGB1, and CD36 in the interconnected network with the combination of Pimozide and Ponatinib represents a promising therapeutic approach for breast cancer.
Primary cilia abnormalities participate in the occurrence of spontaneous abortion through TGF‐β/SMAD2/3 signaling pathway
Authors: Yu Xiaoqin , Li Linyuan , Ning Anfeng , Wang Hu , Guan Chunyi , Ma Xu , Xia Hongfei
Published: May 2024

Spontaneous abortion is the most common complication in early pregnancy, the exact etiology of most cases cannot be determined. Emerging studies suggest that mutations in ciliary genes may be associated with progression of pregnancy loss. However, the involvement of primary cilia on spontaneous abortion and the underlying molecular mechanisms remains poorly understood. We observed the number and length of primary cilia were significantly decreased in decidua of spontaneous abortion in human and lipopolysaccharide (LPS)‐induced abortion mice model, accompanied with increased expression of proinflammatory cytokines interleukin (IL)−1β, IL‐6, and tumor necrosis factor (TNF)‐α. The length of primary cilia in human endometrial stromal cell (hESC) was significantly shortened after TNF‐α treatment. Knocking down intraflagellar transport 88 (IFT88), involved in cilia formation and maintenance, promoted the expression of TNF‐α. There was a reverse regulatory relationship between cilia shortening and TNF‐α expression. Further research found that shortened cilia impair decidualization in hESC through transforming growth factor (TGF)‐β/SMAD2/3 signaling. Primary cilia were impaired in decidua tissue of spontaneous abortion, which might be mainly caused by inflammatory injury. Primary cilia abnormalities resulted in dysregulation of TGF‐β/SMAD2/3 signaling transduction and decidualization impairment, which led to spontaneous abortion.
Ontogenetic changes in jaw leverage and skull shape in tufted and untufted capuchins
Authors: Holmes Megan A. , Terhune Claire E. , Chalk‐Wilayto Janine , Yoakum Caitlin B. , Taylor Parker , Ramirez Rocio , Solís Megan P. , Polvadore Taylor A. , Ross Callum F. , Taylor Andrea B. , Fogaca Mariana Dutra , Laird Myra F.
Published: May 2024

The ontogeny of feeding is characterized by shifting functional demands concurrent with changes in craniofacial anatomy; relationships between these factors will look different in primates with disparate feeding behaviors during development. This study examines the ontogeny of skull morphology and jaw leverage in tufted (Sapajus) and untufted (Cebus) capuchin monkeys. Unlike Cebus, Sapajus have a mechanically challenging diet and behavioral observations of juvenile Sapajus suggest these foods are exploited early in development. Landmarks were placed on three‐dimensional surface models of an ontogenetic series of Sapajus and Cebus skulls (n = 53) and used to generate shape data and jaw‐leverage estimates across the tooth row for three jaw‐closing muscles (temporalis, masseter, medial pterygoid) as well as a weighted combined estimate. Using geometric morphometric methods, we found that skull shape diverges early and shape is significantly different between Sapajus and Cebus throughout ontogeny. Additionally, jaw leverage varies with age and position on the tooth row and is greater in Sapajus compared to Cebus when calculated at the permanent dentition. We used two‐block partial least squares analyses to identify covariance between skull shape and each of our jaw muscle leverage estimates. Sapajus, but not Cebus, has significant covariance between all leverage estimates at the anterior dentition. Our findings show that Sapajus and Cebus exhibit distinct craniofacial morphologies early in ontogeny and strong covariance between leverage estimates and craniofacial shape in Sapajus. These results are consistent with prior behavioral and comparative work suggesting these differences are a function of selection for exploiting mechanically challenging foods in Sapajus, and further emphasize that these differences appear quite early in ontogeny. This research builds on prior work that has highlighted the importance of understanding ontogeny for interpreting adult morphology.
An atlas of anatomical variants of the human calcaneus
Authors: Cockerill Samuel James , Arnay‐de‐la‐Rosa Matilde , González‐Reimers Emilio
Published: May 2024

The usefulness of anatomical variation is determined by the knowledge of why nonmetric traits appear. Clear descriptions of the traits are a necessary task, due to the risk of confusing anatomical variants and evidence of trauma. Numerous interpretations of the appearance of calcaneal anatomical variants add to the need of an anatomical atlas of calcaneal nonmetric traits. We have analyzed a total of 886 calcanei; 559 belong to different modern and pre‐Hispanic samples, and 327 bones were studied from a reference collection from Athens. In this study, we present the anatomical variations that exist on the calcaneus bone, some of which have rarely been mentioned in previous research. The standardization of methods proposed may be useful to experts working in human anatomy, physical anthropology as well as comparative morphology, due to usefulness of this information during surgery, and bioanthropology to observe and study the lifestyle of past populations.