bluuebunny/crossref_metadata_2025 huggingface dataset:
Microstructural Control of a Multi‐Phase PH Steel Printed with Laser Powder Bed Fusion
Authors: Fields Brandon , Amiri Mahsa , Lim Jungyun , Pürstl Julia T. , Begley Matthew R. , Apelian Diran , Valdevit Lorenzo
Published: January 2024

The established approach to materials design for additive manufacturing (AM) consists of attempting to reproduce the uniform structures and properties of conventionally processed materials. While this certainly helped facilitate material certification and the rapid introduction of AM technologies in several industries, the opportunity to exploit unique features of specific AM processes to generate spatially varying microstructures–and hence novel materials, remains largely untapped. This work presents a method for manufacturing materials through laser powder bed fusion (LPBF), in which control over the spatial variation in phase composition and mechanical properties is achieved. This technique is demonstrated using 17‐4 precipitation‐hardened stainless steel (17‐4PH), by controlling spatial modulation of energy densities during printing. This results in local control of ferrite/martensite volume fractions, allowing the fabrication of metal/metal architected composites with hard/brittle regions interspersed with soft/tough regions. Local variations of ~20% in tensile strength and ~150% in elongation are achieved, with a spatial resolution of ~100 microns. The approach is general and robust, fully compatible with commercially available LPBF equipment, and applicable to virtually any multi‐phase alloy system. This work shifts the paradigm from attempting to print components with uniform properties to manufacturing alloys with controlled spatial property gradients.
Enhanced Performance of Gallium‐Based Wide Bandgap Oxide Semiconductor Heterojunction Photodetector for Solar‐Blind Optical Communication via Oxygen Vacancy Electrical Activity Modulation
Authors: Wu Chao , Zhao Tianli , He Huaile , Hu Haizheng , Liu Zeng , Wang Shunli , Zhang Fabi , Wang Qinfeng , Liu Aiping , Wu Fengmin , Guo Daoyou
Published: January 2024

Gallium oxide (β‐Ga2O3) is a prominent representative of the new generation of wide‐bandgap semiconductors, boasting a bandgap of ≈4.9 eV. However, the growth process of β‐Ga2O3 materials introduces unavoidable oxygen vacancies (Vo), leading to persistent photoconductivity (PPC), a phenomenon that severely hinders device performance. In this study, an innovative approach is successfully developed by introducing high p‐orbital energy nitrogen (N). This leads to the formation of a hybridized state with O 2p orbitals in β‐Ga2O3, resulting in the creation of GaON and suppressing the electrical activity of Vo. Through meticulous experimentation and advanced computational methods, a comprehensive and insightful explanation of the regulation and mechanism underlying this passivation process is offered. Moreover, pn‐junction solar‐blind photodetectors are engineered using hybridized GaON thin films with p‐type CuPc. These photodetectors demonstrate exceptional characteristics, including ultra‐low dark current (10−14 A), high photo‐to‐dark current ratio (106), and rapid decay speed (0.008 s) even at zero bias. Based on these advancements, a solar‐blind ultraviolet communication system is designed, featuring straightforward and reliable encoding, easy implementation, and robust anti‐interference capabilities.
Gate‐Tunable Spectral Response in β‐Ga2O3/Te Hybrid Photogating Structure for Ultrasensitive Broadband Detection
Authors: Liu Weijie , Peng Meng , Yu Yiye , Zheng Zhihua , Jian Pengcheng , Zhao Yongming , Zeng Yuhui , Xu Dan , Chen Maohua , Luo Yuang , Chen Changqing , Dai Jiangnan , Wu Feng
Published: January 2024

The increasing demand for multispectral information acquisition and the complexity of application environments have sparked a growing interest in broadband detection. However, achieving a high level of responsivity across a wide response range remains a significant challenge. Herein, an ultrasensitive broadband phototransistor based on hybrid photogating (HPG) structure is demonstrated, which consisted of a quasi‐2D beta‐phase gallium oxide (β‐Ga2O3) nanoflake as the carrier transport channel and a tellurium (Te) nanoflake as the photogating layer. Attributed to the strong doping influence of the Te nanoflake, a low off‐state current of pA level and a high on/off current ratio of ≈108 are obtained. Upon 255 nm wavelength illumination, the device exhibited an ultrahigh responsivity up to 3.82 × 106 A W−1 and a detectivity as high as 1.59 × 1014 Jones across a large gate voltage range. Notably, an exciting infrared response is obtained with a responsivity of 138 A W−1 and a detectivity of 3.70 × 109 Jones under the 1550 nm wavelength illumination, exclusively achievable when the gate voltage exceeded 4 V. Leveraging the gate‐tunable spectral response, an innovative model for secure optical communication was proposed. This work presents an efficient and feasible strategy for fabricating multifunctional optoelectronic devices.
A Catalytic Three‐Component Aminofluorination of Unactivated Alkenes with Electron‐Rich Amino Sources
Authors: Dong Junchao , Liang Yujie , Li Yang , Guan Wei , Zhang Qian , Fu Junkai
Published: January 2024

We present herein a copper‐catalyzed three‐component aminofluorination of unactivated alkenes with N‐bromodialkylamines and readily available nucleophilic fluoride under the assistance of a bidentate auxiliary. This protocol exhibits excellent functional group tolerance toward a wide range of unactivated alkenes and N‐bromodialkylamines to furnish the corresponding β‐fluoroalkylamines in a highly regio‐ and diastereoselective manner. The appropriate choice of nucleophilic fluoro source is essential to make this reaction a reality. Further DFT calculations show that the exothermic ion exchange between external fluoride ion and Cu(II) intermediate provides additional driving force to the irreversible migratory insertion, which offsets the unfavorable reaction energetics associated with the subsequent C(sp3)–F reductive elimination. This finding offers a new avenue to catalytic intermolecular aminofluorination of unactivated alkenes with electron‐rich amino sources via a remarkable reductive elimination of Cu(III) species to forge the C(sp3)–F bonds.
Personalized Porous Gelatin Methacryloyl Sustained‐Release Nicotinamide Protects Against Noise‐Induced Hearing Loss
Authors: Feng Baoyi , Dong Tingting , Song Xinyu , Zheng Xiaofei , Jin Chenxi , Cheng Zhenzhe , Liu Yiqing , Zhang Wenjie , Wang Xueling , Tao Yong , Wu Hao
Published: January 2024

There are no Food and Drug Administration‐approved drugs for treating noise‐induced hearing loss (NIHL), reflecting the absence of clear specific therapeutic targets and effective delivery strategies. Noise trauma is demonstrated results in nicotinamide adenine dinucleotide (NAD+) downregulation and mitochondrial dysfunction in cochlear hair cells (HCs) and spiral ganglion neurons (SGNs) in mice, and NAD+ boosted by nicotinamide (NAM) supplementation maintains cochlear mitochondrial homeostasis and prevents neuroexcitatory toxic injury in vitro and ex vivo, also significantly ameliorated NIHL in vivo. To tackle the limited drug delivery efficiency due to sophisticated anatomical barriers and unique clearance pathway in ear, personalized NAM‐encapsulated porous gelatin methacryloyl (PGMA@NAM) are developed based on anatomy topography of murine temporal bone by micro‐computed tomography and reconstruction of round window (RW) niche, realizing hydrogel in situ implantation completely, NAM sustained‐release and long‐term auditory preservation in mice. This study strongly supports personalized PGMA@NAM as NIHL protection drug with effective inner ear delivery, providing new inspiration for drug‐based treatment of NIHL.
Decreased Expression of IL‐35 and Its Receptor Contributes to Impaired Megakaryopoiesis in the Pathogenesis of Immune Thrombocytopenia
Authors: Cai Xuan , Gui Ruo‐Yun , Wu Jin , Wang Chen‐Cong , Zhu Xiao‐Lu , Fu Hai‐Xia , Zhang Xiao‐Hui
Published: January 2024

Recent findings have shown that the level of interleukin‐35 (IL‐35) is abnormal in several autoimmune diseases. Nonetheless, whether IL‐35 participates in the pathogenesis of immune thrombocytopenia (ITP) remains unclear. The current study investigates whether IL‐35 modulates megakaryopoiesis. The results show that IL‐35 receptors are progressively expressed on bone marrow megakaryocytes during the in vitro differentiation of CD34+ progenitors. IL‐35 increases the number of megakaryocyte colony‐forming units through the Akt pathway. The level of bone marrow IL‐35 is reduced in ITP patients, and the decreased level of IL‐35 may inhibit megakaryopoiesis. Then, the potential causes of decreased IL‐35 in ITP patients are explored. The primary type of cell that secretes IL‐35, known as IL‐35‐producing regulatory T cells (iTr35), is reduced in ITP patients. Bone marrow mesenchymal stem cells (MSCs) from ITP patients exhibit an impaired capability of inducing iTr35 due to enhanced apoptosis, which may contribute to the reduced level of bone marrow IL‐35 in ITP patients. Iguratimod promotes megakaryocyte development and differentiation by elevating the expression of IL‐35 receptors on megakaryocytes. Iguratimod improves response rates and reduces bleeding symptoms in corticosteroid‐resistant ITP patients.
Cocktail Cell‐Reprogrammed Hydrogel Microspheres Achieving Scarless Hair Follicle Regeneration
Authors: Ji Shuaifei , Li Yingying , Xiang Lei , Liu Mingyue , Xiong Mingchen , Cui Wenguo , Fu Xiaobing , Sun Xiaoyan
Published: January 2024

The scar repair inevitably causes damage of skin function and loss of skin appendages such as hair follicles (HF). It is of great challenge in wound repair that how to intervene in scar formation while simultaneously remodeling HF niche and inducing in situ HF regeneration. Here, chemical reprogramming techniques are used to identify a clinically chemical cocktail (Tideglusib and Tamibarotene) that can drive fibroblasts toward dermal papilla cell (DPC) fate. Considering the advantage of biomaterials in tissue repair and their regulation in cell behavior that may contributes to cellular reprogramming, the artificial HF seeding (AHFS) hydrogel microspheres, inspired by the natural processes of “seeding and harvest”, are constructed via using a combination of liposome nanoparticle drug delivery system, photoresponsive hydrogel shell, positively charged polyamide modification, microfluidic and photocrosslinking techniques. The identified chemical cocktail is as the core nucleus of AHFS. In vitro and in vivo studies show that AHFS can regulate fibroblast fate, induce fibroblast‐to‐DPC reprogramming by activating the PI3K/AKT pathway, finally promoting wound healing and in situ HF regeneration while inhibiting scar formation in a two‐pronged translational approach. In conclusion, AHFS provides a new and effective strategy for functional repair of skin wounds.
Theoretical Design and Synthesis of Caged Compounds Using X‐Ray‐Triggered Azo Bond Cleavage
Authors: Ogawara Koki , Inanami Osamu , Takakura Hideo , Saita Kenichiro , Nakajima Kohei , Kumar Sonu , Ieda Naoya , Kobayashi Masato , Taketsugu Tetsuya , Ogawa Mikako
Published: January 2024

Caged compounds are frequently used in life science research. However, the light used to activate them is commonly absorbed and scattered by biological materials, limiting their use to basic research in cells or small animals. In contrast, hard X‐rays exhibit high bio‐permeability due to the difficulty of interacting with biological molecules. With the main goal of developing X‐ray activatable caged compounds, azo compounds are designed and synthesized with a positive charge and long π‐conjugated system to increase the reaction efficiency with hydrated electrons. The azo bonds in the designed compounds are selectively cleaved by X‐ray, and the fluorescent substance Diethyl Rhodamine is released. Based on the results of experiments and quantum chemical calculations, azo bond cleavage is assumed to occur via a two‐step process: a two‐electron reduction of the azo bond followed by N─N bond cleavage. Cellular experiments also demonstrate that the azo bonds can be cleaved intracellularly. Thus, caged compounds that can be activated by an azo bond cleavage reaction promoted by X‐ray are successfully generated.
Fully Reversible and Super‐Fast Photo‐Induced Morphological Transformation of Nanofilms for High‐Performance UV Detection and Light‐Driven Actuators
Authors: Liu Xiangquan , Hu Jiahui , Yang Jinglun , Peng Lingya , Tang Jiaqi , Wang Xiaohui , Huang Rongrong , Liu Jianfei , Liu Kaiqiang , Wang Tingyi , Liu Xiaoyan , Ding Liping , Fang Yu
Published: January 2024

Flexible and highly ultraviolet (UV) sensitive materials garner considerable attention in wearable devices, adaptive sensors, and light‐driven actuators. Herein, a type of nanofilms with unprecedented fully reversible UV responsiveness are successfully constructed. Building upon this discovery, a new system for ultra‐fast, sensitive, and reliable UV detection is developed. The system operates by monitoring the displacement of photoinduced macroscopic motions of the nanofilms based composite membranes. The system exhibits exceptional responsiveness to UV light at 375 nm, achieving remarkable response and recovery times of < 0.3 s. Furthermore, it boasts a wide detection range from 2.85 µW cm−2 to 8.30 mW cm−2, along with robust durability. Qualitative UV sensing is accomplished by observing the shape changes of the composite membranes. Moreover, the composite membrane can serve as sunlight‐responsive actuators for artificial flowers and smart switches in practical scenarios. The photo‐induced motion is ascribed to the cis–trans isomerization of the acylhydrazone bonds, and the rapid and fully reversible shape transformation is supposed to be a synergistic result of the instability of the cis‐isomers acylhydrazone bonds and the rebounding property of the networked nanofilms. These findings present a novel strategy for both quantitative and qualitative UV detection.
Photoactivatable Nanobody Conjugate Dimerizer Temporally Resolves Tiam1‐Rac1 Signaling Axis
Authors: Zhou Chengjian , He Huiping , Chen Xi
Published: January 2024

The precise spatiotemporal dynamics of protein activities play a crucial role in cell signaling pathways. To control cellular functions in a spatiotemporal manner, a powerful method called photoactivatable chemically induced dimerization (pCID) is used. In this study, photoactivatable nanobody conjugate inducers of dimerization (PANCIDs) is introduced, which combine pCID with nanobody technology. A PANCID consists of a nanobody module that directly binds to an antigenic target, a photocaged small molecule ligand, and a cyclic decaarginine (cR10*) cell‐penetrating peptide (CPP) for efficient nonendocytic intracellular delivery. Therefore, PANCID photodimerizers also benefit from nanobodies, such as their high affinities (in the nm or pm range), specificities, and ability to modulate endogenous proteins. Additionally it is demonstrated that the nanobody moiety can be easily replaced with alternative ones, expanding the potential applications. By using PANCIDs, the dynamics of the Tiam1‐Rac1 signaling cascade is investigated and made an interesting finding. It is found that Rac1 and Tiam1 exhibit distinct behaviors in this axis, acting as time‐resolved “molecular oscillators” that transit between different functions in the signaling cascade when activated either slowly or rapidly.
Gas‐Phase Electronic Structure of Phthalocyanine Ions: A Study of Symmetry and Solvation Effects
Authors: Bergmeister Stefan , Ganner Lisa , Ončák Milan , Gruber Elisabeth
Published: January 2024

Research into and applications of phthalocyanines (Pc) are mostly connected to their intriguing electronic properties. Here, messenger‐type UV–vis spectroscopy of two metal‐free ions from the phthalocyanine family, cationic H2Pc+ and H2PcD+, along with their hydrates is performed. They show that the electronic properties of both ions can be traced to those in the conjugate base, Pc2–, however, they are affected by state splitting due to the reduced symmetry; in the H2Pc+ radical cation, a new band appears due to excitations into the singly‐occupied molecular orbital. Quantum chemical spectra modeling reproduces all important features of the measured spectra and provides insight into the nature of electronic transitions. Hydration of the ions has only a mild effect on the electronic spectra, showing the stability of the electronic structure with respect to solvation effects.
A Safe Organic/Inorganic Composite Anode for Sodium‐Ion Batteries
Authors: Li Zhi , Zhang Yu , Zhou Kang , Kong Taoyi , Zhou Xing , Hao Yaming , Huang Xin , Xu Jie , Cheng Yuwen , Liu Haimei , Guo Ziyang , Wang Yonggang
Published: January 2024

Sodium‐ion batteries (SIBs), based on hard carbon anodes and Na+‐intercalation compound cathodes, have gained significant attention. Nonetheless, hard carbon anodes involve the storage of Na+ at a low potential, typically below 0.1 V (vs Na/Na+), which increases the risk of dendritic Na growth on the anode surface during overcharging. Herein, a safe organic/inorganic composite anode containing tetrasodium 3,4,9,10‐perylenetetracarboxylate (Na4PTC) and Metallic bismuth (Bi) with a weight ratio of 7:2, which exhibits an average potential of 0.7 V (vs Na+/Na) and a capacity of 150 mAh g−1 is proposed. The electrode reaction involves a reversible coordination reaction within the organic host and alloying reactions within the metallic Bi component. Importantly, the organic component efficiently buffers the volume changes in Bi during the alloying reaction, while the metallic Bi enhances the electronic conductivity of the organic material. As a result, this composite anode shows high cycle stability and rate performance, even under high mass loadings ranging from 10 to 50 mg cm−2. Furthermore, it is demonstrated that the Na‐ion full cell, consisting of the composite anode and the Na3V2O2(PO4)2F cathode, exhibits minimal capacity degradation over 100 cycles while maintaining a high areal capacity of 1.1 mA cm−2.
The current landscape of emergency medicine resident scheduling
Authors: Parsons Melissa , Mannix Alexandra , Gore Katarzyna , Rabalais Jeanne , Gottlieb Michael
Published: January 2024

Background

The Accreditation Council for Graduate Medical Education (ACGME) and Residency Review Committee oversee resident physician work hours with additional specifics for U.S. emergency medicine (EM) residency programs. While there are maximum work hours, the regulatory bodies do not describe minimum work hours to achieve competency, leading to variable scheduling practices. This study aimed to understand the current landscape of U.S. EM residency scheduling given the expansion of programs, evolution of policies, and increased emphasis on wellness.

Methods

We conducted a cross‐sectional study to assess current strategies of U.S. EM residency scheduling. The RedCap survey was sent to all ACGME‐accredited EM residency programs across the United States via individualized emails between January 10, 2023, and March 15, 2023. Data were combined using Microsoft Excel.

Results

A total of 138 of 278 (50%) programs responded to the survey. A total of 73.2% of programs were using thirteen 28‐day blocks with the remainder using twelve 1‐month blocks or reported “other” block scheduling. The number of blocks in the ED increases with each postgraduate year (PGY). For PGY‐1 through PGY‐3, the most commonly used shift duration was 9 h. The mean total shifts per ED block and hours worked per ED block are as follows: 19 shifts and 185.1 h (PGY‐1), 18.2 shifts and 173.9 h (PGY‐2), 17.3 shifts and 163.6 h (PGY‐3), and 14.8 shifts and 157.2 h (PGY‐4). Programs provide a median for 4 weeks of vacation per year of residency.

Conclusions

Given the expansion of U.S. EM residency programs, we reevaluated the landscape of resident scheduling. We described scheduling patterns related to night shifts, vacations, requested time off, conference coverage, charting time, and circadian rhythms. Programs should utilize these data as a starting point for setting a clinical experience for their residents.
Tactile‐Based Negotiation of Unknown Objects during Navigation in Unstructured Environments with Movable Obstacles
Authors: Armleder Simon , Dean‐Leon Emmanuel , Bergner Florian , Guadarrama Olvera Julio Rogelio , Cheng Gordon
Published: January 2024

Traditional robot navigation passively plans/replans to avoid any contact with obstacles in the scene. This limits the obtained solutions to the collision‐free space and leads to failures if the path to the goal is obstructed. In contrast, humans actively modify their environment by repositioning objects if it assists locomotion. This article aims to bring robots closer to such abilities by providing a framework to detect and clear movable obstacles to continue navigation. The approach leverages a multimodal robot skin that provides both local proximity and tactile feedback regarding physical interactions with the surroundings. This multimodal contact feedback is employed to adapt the robot's behavior when interacting with object surfaces and regulating applied forces. This enables the robot to remove bulky obstacles from its path and solves otherwise infeasible navigation problems. The system's ability is demonstrated in simulation and real‐world scenarios involving movable and nonmovable obstacles.
Nitrogenous Intermediates in NOx‐involved Electrocatalytic Reactions
Authors: Jia Shunhan , Wu Limin , Liu Hanle , Wang Ruhan , Sun Xiaofu , Han Buxing
Published: January 2024

Chemical manufacturing utilizing renewable sources and energy emerges as a promising path towards sustainability and carbon neutrality. The electrocatalytic reactions involving nitrogen oxides (NOx) offered a potential strategy for synthesizing various nitrogenous chemicals. However, it is currently hindered by low selectivity/efficiency and limited reaction pathways, mainly due to the difficulties in controllable generation and utilization of nitrogenous intermediates. In this minireview, focusing on nitrogenous intermediates in NOx‐involved electrocatalytic reactions, we discuss newly developed methodologies for studying and controlling the generation, conversion, and utilizing of nitrogenous intermediates, which enable recent developments in NOx‐involved electrocatalytic reactions that yield various products, including ammonia (NH3), organonitrogen molecules, and nitrogenous compounds exhibiting unconventional oxidation states. Furthermore, we also make an outlook to highlight future directions in the emerging field of NOx‐involved electrocatalytic reactions.
Gamma radiation‐induced synthesis of polyaniline/CuWO4nanocomposite for potential sorption of cobalt‐60 and cesium‐137 from aqueous solutions
Authors: Abdel Maksoud M. I. A. , Ghobashy Mohamed Mohamady , Aly Mohamed I. , Hassan Reham S. , Ashour A. H.
Published: January 2024

The release of cobalt‐60 and cesium‐137 in the environment is considered dangerous pollutants. In this concern, the present work deals with gamma radiation‐induced synthesis of novel polyaniline/CuWO4(PANi/CWO) nanocomposite adsorbent and estimating its potential adsorption capacity for cobalt‐60 and cesium‐137 from aqueous solution. The crystallite size of pure CWO NPs and PANi/CWO nanocomposite is found in the nanoscale range. Also, SEM images and XRD results confirmed the successful preparation of PANi/CWO nanocomposite. Further, the elemental mapping images proved that all the investigated elements were homogeneously distributed over the PANi/CWO nanocomposite. Besides, the adsorption experiments were conducted separately to investigate the adsorption behavior of cobalt‐60 and cesium‐137 by PANi/CWO nanocomposite. Adsorption processes have also been performed, and numerous factors, including medium pH, contact time, initial metal ion concentration, and temperature, have been tested. Batch experiments were done to get the optimum conditions for removing cobalt‐60 and cesium‐137. Four kinetic models were investigated, indicating that the adsorption process of cobalt‐60 and cesium‐137 onto PANi/CWO nanocomposite is controlled by chemisorption and intra‐particle diffusion. Four equilibrium isotherm models were investigated, revealing that the adsorption process is a monolayer and multilayer process on a heterogeneous surface. The (∆Ho) value suggested that this study's removal of cesium and cobalt has an endothermic behavior, whereas the positive (∆So) value proved that the examined system is random. The effect of temperature was investigated, and the calculated thermodynamic parameters indicated that the removal of cobalt‐60 and cesium‐137 by PANi/CWO nanocomposite has an endothermic behavior.
Innovations in dengue virus detection: An overview of conventional and electrochemical biosensor approaches
Authors: Raza Shadan , Poria Renu , Kala Deepak , Sharma Nishant , Sharma Anil K. , Florien Nkurunziza , Tuli Hardeep S. , Kaushal Ankur , Gupta Shagun
Published: January 2024

Globally, people are in great threat due to the highly spreading of viral infectious diseases. Every year like 100–300 million cases of infections are found, and among them, above 80% are not recognized and irrelevant. Dengue virus (DENV) is an arbovirus infection that currently infects people most frequently. DENV encompasses four viral serotypes, and they each express comparable sign. From a mild febrile sickness to a potentially fatal dengue hemorrhagic fever, dengue can induce a variety of symptoms. Presently, the globe is being challenged by the untimely identification of dengue infection. Therefore, this review summarizes advances in the detection of dengue from conventional methods (nucleic acid‐based, polymerase chain reaction‐based, and serological approaches) to novel biosensors. This work illustrates an extensive study of the current designs and fabrication approaches involved in the formation of electrochemical biosensors for untimely identifications of dengue. Additionally, in electrochemical sensing of DENV, we skimmed through significances of biorecognition molecules like lectins, nucleic acid, and antibodies. The introduction of emerging techniques such as the CRISPR/Cas’ system and their integration with biosensing platforms has also been summarized. Furthermore, the review revealed the importance of electrochemical approach compared with traditional diagnostic methods.
Construction and characterization of a promoter library with varying strengths to enhance acetoin production from xylose in Serratia marcescens
Authors: Liu Jie , Liu Di , Sun Tingting , Fan Tai‐Ping , Cai Yujie
Published: January 2024

Serratia marcescens is utilized as a significant enterobacteria in the production of various high‐value secondary metabolites. Acetoin serves as a crucial foundational compound of development and finds application in a broad range of fields. Furthermore, S. marcescens HBQA‐7 is capable of utilizing xylose as its exclusive carbon source for acetoin production. The objective of this study was to utilize a constitutive promoter screening strategy to enhance both xylose utilization and acetoin production in S. marcescens HBQA‐7. By utilizing RNA‐seq, we identified the endogenous constitutive promoter P6 that is the most robust, which facilitated the overexpression of the sugar transporter protein GlfL445I, α‐acetyl lactate synthase, and α‐acetyl lactate decarboxylase, respectively. The resultant recombinant strains exhibited enhanced xylose utilization rates and acetoin yields. Subsequently, a recombinant plasmid, denoted as pBBR1MCS‐P6‐glfL445IalsSalsD, was constructed, simultaneously expressing the aforementioned three genes. The resulting recombinant strain, designated as S3, demonstrated a 1.89‐fold boost in xylose consumption rate compared with the original strain during shake flask fermentation. resulting in the accumulation of 7.14 g/L acetoin in the final fermentation medium. Subsequently, in a 5 L fermenter setup, the acetoin yield reached 48.75 g/L, corresponding to a xylose‐to‐acetoin conversion yield of 0.375 g/g.
A Mutagen Acts as a Potent Reducing Agent of Glycated Hemoglobin: a Combined Ultrafast Electron Transfer and Computational Studies
Authors: Roy Lopamudra , Pan Nivedita , Ghosh Ria , Hasan Md. Nur , Mondal Susmita , Banerjee Amrita , Das Monojit , Sen Oyshi , Bhattacharya Kallol , Chattopadhyay Arpita , Pal Samir Kumar
Published: January 2024

Glycated hemoglobin (GHb) found in mammals undergoes irreversible damage when exposed to external redox agents, which is much more vulnerable than its normal counterpart hemoglobin (Hb). Besides the oxygen regulation throughout the body, Hb plays a vital role in balancing immunological health and the redox cycle. Photoinduced ultra‐fast electron transfer phenomena actively participate in regulation of various kind of homeostasis involved in such biomacromolecules. In the present study we have shown that a well‐known mutagen Ethidium Bromide (EtBr) reduces GHb in femtosecond time scale (efficiently) upon photoexcitation after efficient recognition in the biomolecule. We have performed similar experiment by colocalizing EtBr and Iron (Fe(III)) on the micellar surface as Hb mimic in order to study the excited state EtBr dynamics to rationalize the time scale obtained from EtBr in GHb and Hb. While other experimental techniques including Dynamic Light Scattering (DLS), Zeta potential, absorbance and emission spectroscopy have been employed for the confirmation of structural perturbation of GHb compared to Hb, a detailed computational studies involving molecular docking and density functional theory (DFT) have been employed for the explanation of the experimental observations.
Structural‐Functional Correlations between Unique N‐terminal Region and C‐terminal Conserved Motif in Short‐chain cis‐Prenyltransferase from Tomato
Authors: Imaizumi Riki , Matsuura Hiroaki , Yanai Taro , Takeshita Kohei , Misawa Shuto , Yamaguchi Haruhiko , Sakai Naoki , Miyagi‐Inoue Yukino , Suenaga‐Hiromori Miki , Waki Toshiyuki , Kataoka Kunishige , Nakayama Toru , Yamamoto Masaki , Takahashi Seiji , Yamashita Satoshi
Published: January 2024

Neryl diphosphate (C10) synthase (NDPS1), a homodimeric soluble cis‐prenyltransferase from tomato, contains four disulfide bonds, including two inter‐subunit S−S bonds in the N‐terminal region. Mutagenesis studies demonstrated that the S−S bond formation affects not only the stability of the dimer but also the catalytic efficiency of NDPS1. Structural polymorphs in the crystal structures of NDPS1 complexed with its substrate and substrate analog were identified by employing massive data collections and hierarchical clustering analysis. Heterogeneity of the C‐terminal region, including the conserved RXG motifs, was observed in addition to the polymorphs of the binding mode of the ligands. One of the RXG motifs covers the active site with an elongated random coil when the ligands are well‐ordered. Conversely, the other RXG motif was located away from the active site with a helical structure. The heterogeneous C‐terminal regions suggest alternating structural transitions of the RXG motifs that result in closed and open states of the active sites. Site‐directed mutagenesis studies demonstrated that the conserved glycine residue cannot be replaced. We propose that the putative structural transitions of the order/disorder of N‐terminal regions and the closed/open states of C‐terminal regions may cooperate and be important for the catalytic mechanism of NDPS1.
Time‐weighted blood pressure with cardiovascular risk among patients with or without diabetes
Authors: Jiang Zhixin , Shao Fang , Hu Jingwen , Zhuang Qinyuan , Cooray Pestheruwe Liyanaralalage Rosemarrie Krisunika , Chen Kangyu , Wu Zhenqiang , Chen Tao , Li Chao
Published: January 2024

Background

Usual measures of blood pressure (BP) do not account for both the magnitude and duration of exposure to elevated BP over time. We aimed to demonstrate the effect of a novel time‐weighted BP on cardiovascular outcomes using a post hoc analysis of two published randomized trials.

Hypothesis

Time‐weighted blood pressure is associated with cardiovascular risk among patients with or without diabetes.

Methods

The limited‐access ACCORD and SPRINT data sets were used for the current study. Time‐weighted BP is obtained by dividing cumulative BP by the total follow‐up time. Time‐weighted BP burden above a threshold is also determined after deriving the time‐weighted BP by re‐zeroing the interpolated pressure values at two different hypertension thresholds (>140/90 and >130/80 mmHg).

Results

Eighteen thousand five hundred forty‐one patients from the two clinical trials were enrolled in this study. A J‐curve relation was observed between time‐weighted BP and major cardiovascular events (MACE). The systolic blood pressure (SBP) burden independently predicted MACE across the two trials at different thresholds (ACCORD: SBP > 130 mmHg, HR = 1.05 [1.03−1.06]; SBP > 140 mmHg, HR = 1.06 [1.04−1.08]; SPRINT: SBP > 130 mmHg, HR = 1.04 [1.03−1.05]; SBP > 140 mmHg, HR = 1.05 [1.04−1.07]). Consistent results were found for diastolic blood pressure (DBP) burden (ACCORD: DBP > 80 mmHg, HR = 1.10 [1.06−1.15]; DBP > 90 mmHg, HR = 1.20 [1.11−1.30]. SPRINT: DBP > 80 mmHg, HR = 1.06 [1.02−1.09]; DBP > 90 mmHg, HR = 1.12 [1.06−1.18]). Significant associations were also observed for stroke, myocardial infarction, cardiovascular death, and all‐cause mortality.

Conclusion

Both time‐weighted SBP and DBP independently influenced the risk of adverse cardiovascular events among patients with and without diabetes, regardless of the definition of hypertension (130/80 or <140/90 mmHg).
In‐silico and in‐vitro evidence suggest LINC01405 as a sponge for miR‐29b and miR‐497‐5p, and a potential regulator of Wnt, PI3K, and TGFB signaling pathways in breast carcinoma
Authors: Norouzi Romina , Mohamadzade Zahra , Norouzi Rambod , Norouzi Radin , Esmaeili Rezvan , Soltani Bahram M.
Published: January 2024

Background

Carcinoma of the breast, a prevailing factor in female mortality worldwide, involves dysregulation of lncRNAs and microRNAs.

Aim

The main goal of this research was to predict and experimentally examine the LINC01405 expression status in breast cancer subtypes, along with investigation of its interaction with miR‐29b and miR‐497‐5p that results in regulating PI3‐Kinase, WNT, and TGF‐beta signaling pathways.

Methods and Results

We performed a meta‐analysis of five GEO datasets, encompassing microarray and RNA‐seq data, to identify differentially expressed genes. The Cancer Genome Atlas transcriptome dataset was also analyzed to determine essential gene modules, associated with different stages of breast cancer by weighted gene co‐expression networks. In addition, networks of drug‐gene interactions were constructed to explore potential treatment options. LINC01405 as a microRNA sponge was chosen and examined. furthermore, downstream target genes were discovered.

Experimental validation consisted of plasmid constructs used in cell culture experiments, RT‐qPCR for expression analysis, and cell cycle assays. Our bioinformatics findings showed higher LINC01405 expression in Basal‐like triple‐negative breast carcinoma. In contrast, lower expression in Luminal samples was observed compared with normal samples, which was consistently observed in both breast cancer tissues and cell lines. LINC01405 expression level was correlated with miR‐29b and miR‐497 levels. The MDA‐MB‐231 cell line demonstrated higher LINC01405 expression and lower miR‐29b and miR‐497 expression levels. However, SKBR3 and MCF7 cells had lower LINC01405 expression and higher miR‐29b and miR‐497 levels, suggesting a regulatory role for LINC01405 as a competing endogenous RNA. This was experimentally confirmed when LINC01405 was overexpressed in SKBR3 cells, and the common target genes of miR‐29b and miR‐497 were upregulated. Additionally, LINC01405 upregulation led to the increased cell populations, proliferation, and upregulation of critical cancer‐related genes, including AKT1, AKT3, mTOR, WNT3A, SMAD3, CYCLIN D1, CYCLIN D2, BCL2, and GSK3B.

Conclusion

We revealed the differential expression of LINC01405 in several types of breast cancer and its role in regulating signaling pathways, potentially via scavenging miRNAs. These findings clarified the role of LINC01405 in breast cancer development and identified potential therapeutic targets.
Rise in child suicide linked to reduced quality of life, parental addiction
Authors: Knopf Alison
Published: January 2024

After generally declining for decades, suicide rates among children aged 10–17 rose dramatically from 2011 to 2018, according to an article released in December 2023. The author, from RAND, writes that the illicit opioid crisis is responsible. This began with the August 2010 introduction of an abuse‐resistant form of the painkiller OxyContin. No longer available for abuse, the drug was replaced on the street first by heroin and then by other illicit opioids including fentanyl. The researcher found that the areas most exposed to the reformulated OxyContin had a greater rise in child suicides. The researcher suggests that the problem was not an increase in illicit opioid use by children, but rather higher propensities to suicide risk factors such as increasing rates of child neglect and altered household living arrangements — drug use by parents and caregivers. The researcher also documents the decline in living conditions for children during this period. The article documents suicide rates from the National Vital Statistics System Multiple Cause of Death database. Powell, D. (2023, Dec 1). Growth in suicide rates among children during the illicit opioid crisis. Demography, 60(6), 1843–1875. http://doi.org/10.1215/00703370‐11077660.
Three‐phase step‐down AC/DC converter with sinusoidal pulse‐width modulation
Authors: Huang You‐Chun , Hsieh Yao‐Ching , Syu Zih‐Jin
Published: January 2024

This paper proposes a step‐down alternating current (AC)/direct current (DC) converter with current‐doubler rectification stage, therefore suitable for low‐voltage and high‐power applications. High power factor and low harmonic distortion can be achieved by simply applying sinusoidal pulse‐width modulation (SPWM) control. A laboratory prototype circuit rated at 2 kW, 180‐V output voltage is designed and built to verify the circuit feasibility. Experimental results confirm that the power factor is ubiquitously higher than 0.99 from 500 W to the full load. The total harmonic distortion at the full load is less than 5%, which meet the harmonic specifications of IEC 61000‐3‐2 and IEC 61000‐3‐12.
Every mistake is a treasure: Lessons learned from the TRIANGLE trial for anorexia nervosa
Authors: Ambwani Suman , Coull Eliza , Cardi Valentina , Rowlands Katie , Treasure Janet
Published: January 2024

Background

Despite several decades of treatment research for anorexia nervosa (AN), many of the same questions remain: how to boost enrollment, engage participants, prevent attrition, and meet the needs of a diverse patient population within the rigorous framework of a randomized controlled trial (RCT).

Methods

In this research forum, we highlight some of the challenges and opportunities observed over the course of TRIANGLE, the largest RCT for severe AN treatment in the UK to date. We discuss strategies for addressing common challenges and avoiding common pitfalls and propose solutions to future researchers seeking to conduct treatment research in AN.

Results

Our experience underscores the value of involving people with lived experience at every stage of intervention research. We offer additional recommendations for treatment researchers, including, (1) early qualitative research to identify patient barriers and obstacles, (2) clear, systematic collaboration with clinical sites for patient recruitment and passive data collection, (3) careful consideration of assessment metrics, including repeated measurement of quality of life, (4) adopting a flexible, patient‐centered approach to clinical trial research, and (5) considering the unique needs and obstacles that might impact carer participation in research and their ability to provide support to their loved ones.

Discussion

We hope that these lessons learned will prove fruitful for the next generation of researchers embarking on treatment research for AN.

Public Significance

Using the TRIANGLE trial as an illustrative case study, we highlight the value of lived experience and codesign for developing and testing interventions for AN. We offer several lessons learned over the course of the trial, pertaining to trial enrollment, retention and engagement, measurement of outcomes, and research adaptations for real‐world settings, and hope that these recommendations facilitate future treatment research for AN.
Synthesis, Luminescence and Relaxometric Properties of Macrocyclic Lanthanide Complexes Appended with an Imidazothiadiazole, a Heterocyclic Bioactive Scaffold
Authors: Ndiaye Modou , Caillet Emma , Eliseeva Svetlana V. , Masson Thibaut , Marchetti Luke A. , Pallier Agnès , Morfin Jean‐François , Petoud Stéphane , Routier Sylvain , Buron Frédéric , Bonnet Célia S.
Published: January 2024

The syntheses of two macrocycles containing original imidazothiadiazole heterocycles are presented. The protonation constants of the ligands have been determined by potentiometry and photophysical measurements. The photophysical properties of the corresponding Tb3+ complexes have been analyzed and the sensitization of the Tb3+ by the heterocyclic moiety demonstrated with modest quantum yields. The corresponding Gd3+ complexes are monohydrated and display higher relaxivities than GdDOTA, which could be explained by the larger size of these complexes. The different substitutions on the heterocycle do not affect strongly the protonation constants of the ligand, the quantum yield, water exchange rate or relaxation properties of the system.
Research on fuel injection characteristics of common rail system based on high pressure pipeline integration and matching
Authors: Xu Rui‐fan , Ma Fu‐kang , Li Liang‐yu , Yang Wei , Zhang Yi
Published: January 2024

The modular prediction model of high pressure common rail system was established to study the influence of high‐pressure pipeline integration matching on the fuel injection characteristics of common rail system. The influence of common rail volume on pressure building and pressure fluctuation in common rail tubes was analyzed. The influence of common rail volume on the matching of fuel injection frequency (number of fuel injectors) and fuel supply frequency (number of plunger pumps) was studied by using the control variable method, and the basic optimal solution of the system was obtained. The influence of the common rail structure on the fuel flow characteristics of the system was also studied. The matching relationship between high pressure tubing and common rail system is studied by introducing dimensionless numbers such as length‐diameter ratio of pipeline. The results demonstrate that the increase of the storage space of the accumulator can effectively reduce the fluctuation in the system, so that the injection volume increases slowly and then decreases rapidly, with a slope of −5.70 × 10−3 mm3. The increase of the diameter of the common rail makes the fuel flow characteristics become good first and then bad, and the increase of the length of the common rail can soothe the pressure fluctuations. The increase of the diameter of the link tube (LT) makes the fuel injection volume of the injector increase first and then decrease. The optimal VR solution for the LT is 0.0249 and the optimal ratio of the length to diameter of a pipeline solution is 55.10. The structure of the distribution tube and its matching to the common rail have little effect on the fuel flow characteristics. When the diameter and length of the injection tube are too large, the influence on the injection pressure of the injector is negatively correlated.
Labile silver(I) complexes with benzisothiazolinone anion and phosphines: Synthesis, characterization and hydrogen storage application
Authors: Alheety Mustafa A. , Aljibori Subhi A. , Nuaman Huda A. , Majeed Abdulwahhab H. , Singh Pramod K. , Shalu  , Yahya M. Z. A.
Published: January 2024

A silver complex was prepared with benzisothiazolinone ligand, which was used to prepare new phosphorus‐rich complexes with dppe and dppp. All complexes were diagnosed by FTIR, 1H‐NMR, 31P‐NMR, CHN, and molar conductivity. The results proved that phosphines were labile, therefore 31P‐NMR was measured by cryoprotection at different temperatures. As a promoted effort to obtain direct experimental proof for the dimeric and the labile nature of [Ag(bit)(diphos)]2 complexes in solution, the 31P{1H}‐NMR spectrum of mixed (dppe/dppp) ligand complexes was measured. It was anticipated that an exchange of phosphines occurred between [Ag(bit)(dppe)]2 and [Ag(bit)(dppp)]2 complexes. However, a distribution of the dppp and dppe should result, and complex with compositions of [Ag2(bit)2(dppe)(dppp)] will be formed. The phosphine‐containing complexes were used in hydrogen storage study. The results proved that hydrogen storage values were initially similar for [Ag(bit)(dppp)]2 and [Ag(bit)(dppe)]2, but increased significantly for [Ag(bit)(dppe)]2 at higher pressures to reach 4.35 wt% at 90 bar.
Immunosuppressive therapy and COVID‐19 infection in patients with NMOSD
Authors: Choi Un Wai , Ai Xiwen , Li Hongyan , Hao Yong , Yao Xiaoying , Guan Yangtai
Published: January 2024

Introduction

To evaluate whether treated with immunosuppressants in neuromyelitis optica spectrum disorder (NMOSD) shows an effect on the severity and outcomes of COVID‐19 Omicron variant.

Methods

This is a substudy of a single‐center clinical trial involving human umbilical cord mesenchymal stem cells (hUC‐MSCs) in NMOSD patients. NMOSD patients with hUC‐MSCs treatment, NMOSD patients without hUC‐MSCs treatment, and matched healthy controls (HC) were included. Demographic information, NMOSD‐related clinical features, comorbidities, use of disease‐modifying therapy, COVID‐19 vaccination status, COVID‐19 clinical features, COVID‐19 clinical outcomes, and NMOSD‐related disease activity were obtained through online questionnaires or phone calls.

Results

The majority of NMOSD patients received long‐term treatment with mycophenolate mofetil (68.8%) or azathioprine (22.9%), and 50% received oral glucocorticoid. During the epidemic, 97.4% of NMOSD patients infected with COVID‐19 had asymptomatic or mild forms, with only two patients (2.6%) requiring hospitalization. None of these patients required tracheal intubation or admission to the intensive care unit. Clinical symptoms were found to be more prevalent in HC groups. Additionally, the HC groups had higher fever‐recorded temperatures. NMOSD patients who received hUC‐MSCs treatment had shorter disease duration than patients who did not receive hUC‐MSCs treatment.

Discussion

Immunosuppressant‐treated patients with NMOSD have a similar risk of COVID‐19 infection as the general population, but the disease duration is shorter and the clinical symptoms are less severe. Among our NMOSD patients who received hUC‐MSCs treatment, COVID‐19 outcomes were favorable, with no increased risk of severe COVID‐19. Prospective studies on immunotherapies are needed to help determine best treatment practices.