bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting C21orf58 is a Novel Treatment Strategy of Hepatocellular Carcinoma by Disrupting the Formation of JAK2/C21orf58/STAT3 Complex
Authors: Jiang Hao , Wang Yang , Wen Doudou , Yu Rongji , Esa Sayed S , Lv Kefeng , Feng Qing , Liu Jing , Li Faxiang , He Lan , Di Xiaotang , Zhang Shubing
Published: February 2024

Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death worldwide. Functionally uncharacterized genes are an attractive repository to explore candidate oncogenes. It is demonstrated that C21orf58 displays an oncogenic role in promoting cell growth, tumorigenesis and sorafenib resistance of HCC cells by abnormal activation of STAT3 signaling. Mechanistically, a novel manner to regulate STAT3 signaling that adaptor C21orf58 forms a ternary complex is reveal with N‐terminal domain of STAT3 and SH2 domain of JAK2, by which C21orf58 overactivates wild‐type STAT3 by facilitating its phosphorylation mediated by JAK2, and hyper‐activates of constitutively mutated STAT3 due to preferred binding with C21orf58 and JAK2. Moreover, it is validated that inhibition of C21orf58 with drug alminoprofen, selected by virtual screening, could effectively repress the viability and tumorigenesis of HCC cells. Therefore, it is identified that C21orf58 functions as an oncogenic adaptor, reveal a novel regulatory mechanism of JAK2/STAT3 signaling, explain the cause of abnormal activity of activated mutants of STAT3, and explore the attractive therapeutic potential by targeting C21orf58 in HCC.
An Integrated Arterial Remodeling Hydrogel for Preventing Restenosis After Angioplasty
Authors: Fu Chenxing , Li Qiu , Li Minghui , Zhang Jiexin , Zhou Feiran , Li Zechuan , He Dongyue , Hu Xinyi , Ning Xiaodong , Guo Wenjie , Li Weirun , Ma Jing , Chen Guoqin , Xiao Yafang , Ou Caiwen , Guo Weisheng
Published: February 2024

The high incidence of restenosis after angioplasty has been the leading reason for the recurrence of coronary heart disease, substantially increasing the mortality risk for patients. However, current anti‐stenosis drug‐eluting stents face challenges due to their limited functions and long‐term safety concerns, significantly compromising their therapeutic effect. Herein, a stent‐free anti‐stenosis drug coating (denoted as Cur‐NO‐Gel) based on a peptide hydrogel is proposed. This hydrogel is formed by assembling a nitric oxide (NO) donor‐peptide conjugate as a hydrogelator and encapsulating curcumin (Cur) during the assembly process. Cur‐NO‐Gel has the capability to release NO upon β‐galactosidase stimulation and gradually release Cur through hydrogel hydrolysis. The in vitro experiments confirmed that Cur‐NO‐Gel protects vascular endothelial cells against oxidative stress injury, inhibits cellular activation of vascular smooth muscle cells, and suppresses adventitial fibroblasts. Moreover, periadventitial administration of Cur‐NO‐Gel in the angioplasty model demonstrate its ability to inhibit vascular stenosis by promoting reendothelialization, suppressing neointima hyperplasia, and preventing constrictive remodeling. Therefore, the study provides proof of concept for designing a new generation of clinical drugs in angioplasty.
Light Color‐Controlled pH‐Adjustment of Aqueous Solutions Using Engineered Proteoliposomes
Authors: Harder Daniel , Ritzmann Noah , Ucurum Zöhre , Müller Daniel J. , Fotiadis Dimitrios
Published: February 2024

Controlling the pH at the microliter scale can be useful for applications in research, medicine, and industry, and therefore represents a valuable application for synthetic biology and microfluidics. The presented vesicular system translates light of different colors into specific pH changes in the surrounding solution. It works with the two light‐driven proton pumps bacteriorhodopsin and blue light‐absorbing proteorhodopsin Med12, that are oriented in opposite directions in the lipid membrane. A computer‐controlled measuring device implements a feedback loop for automatic adjustment and maintenance of a selected pH value. A pH range spanning more than two units can be established, providing fine temporal and pH resolution. As an application example, a pH‐sensitive enzyme reaction is presented where the light color controls the reaction progress. In summary, light color‐controlled pH‐adjustment using engineered proteoliposomes opens new possibilities to control processes at the microliter scale in different contexts, such as in synthetic biology applications.
A Polymer Nanocomposite with Strong Full‐Spectrum Solar Absorption and Infrared Emission for All‐Day Thermal Energy Management and Conversion
Authors: Li Xiangxin , Zhang Zipeng , Zhang Xueting , Cao Yanxia , Yang Yanyu , Wang Wanjie , Wang Jianfeng
Published: February 2024

Realizing efficient energy utilization from the heat source of the sun and the cold source of outer space is of great significance for addressing the global energy and environmental crisis. Materials with ideal full‐spectrum solar absorption and infrared emission are highly desirable for adapting to the continuous weather dynamic throughout the day, nonetheless, their development remains challenging. Here, a polymer nanocomposite with full‐spectrum strong solar (280–2500 nm) absorption ranging from 88.8% to 94.8% with an average value of 93.2% and full‐spectrum high infrared (8–13 µm) emission ranging from 81.3% to 90.0% with an average value of 84.2%, is reported by melt‐processing polypropylene and uniformly dispersed low‐loading MXene nanosheets (1.9 vol%). The nanocomposite can achieve daytime photothermal enhancement of ≈50 °C and nighttime radiative cooling of 8 °C. The temperature difference throughout the day ensures all‐day uninterrupted thermoelectric generation, yielding a power density output of 1.5 W m−2 (daytime) and 7.9 mW m−2 (nighttime) in real outdoor environment without any additional energy consumption. This work provides an impressive polymer nanocomposite with ideal full‐spectrum solar absorption and infrared emission for all‐day uninterrupted thermal energy management and conversion.
Fabrication of Interface Engineered S‐Scheme Heterojunction Nanocatalyst for Ultrasound‐Triggered Sustainable Cancer Therapy
Authors: Yuan Meng , Yang Ling , Yang Zhuang , Ma Zhizi , Ma Jie , Liu Zhendong , Ma Ping'an , Cheng Ziyong , Maleki Aziz , Lin Jun
Published: February 2024

In order to establish a set of perfect heterojunction designs and characterization schemes, step‐scheme (S‐scheme) BiOBr@Bi2S3 nanoheterojunctions that enable the charge separation and expand the scope of catalytic reactions, aiming to promote the development and improvement of heterojunction engineering is developed. In this kind of heterojunction system, the Fermi levels mediate the formation of the internal electric field at the interface and guide the recombination of the weak redox carriers, while the strong redox carriers are retained. Thus, these high‐energy electrons and holes are able to catalyze a variety of substrates in the tumor microenvironment, such as the reduction of oxygen and carbon dioxide to superoxide radicals and carbon monoxide (CO), and the oxidation of H2O to hydroxyl radicals, thus achieving sonodynamic therapy and CO combined therapy. Mechanistically, the generated reactive oxygen species and CO damage DNA and inhibit cancer cell energy levels, respectively, to synergistically induce tumor cell apoptosis. This study provides new insights into the realization of high efficiency and low toxicity in catalytic therapy from a unique perspective of materials design. It is anticipated that this catalytic therapeutic method will garner significant interest in the sonocatalytic nanomedicine field.
Solar Thermal Energy Storage Systems Based on Discotic Nematic Liquid Crystals That Can Efficiently Charge and Discharge below 0 °C
Authors: Gupta Monika , Ashy
Published: February 2024

Solid‐state solar thermal fuels (SSTFs) serve as efficient means of storing solar energy as chemical potential energy in a closed loop system and releasing it as heat on‐demand. An ideal SSTF requires photoswitchability in visible‐region without any external heating as well as extended storage times. However, existing systems often rely on ultraviolet (UV) light or heating for photoswitching, or suffer from low storage times. Addressing this, a novel strategy is presented to obtain visible‐light responsive SSTFs designed to operate effectively at room‐temperature or sub‐zero temperatures by innovatively integrating a tetra‐ortho‐fluoro/chloro azobenzene arm in triphenylene based liquid crystal (LC) moiety. The resulting compounds exhibit discotic nematic (ND) mesophases till −6.5 °C. These compounds exhibit excellent photocyclability, photostability, and sufficient half‐lives of cis states. Achieving up to 77% charging under sunlight with a bandpass filter and 62.4% without it, these systems uniquely demonstrate efficient chargeability and dischargeability at sub‐zero temperatures. Upon discharging, temperature rise of up to 6.5 and 29.5 °C occur at room‐temperature (25 °C) and sub‐zero temperatures (around −6 to −7 °C), respectively. This efficacy is attributed to less‐ordered ND phases providing conformational freedom for photoisomerization at low temperatures.
How Solvation Energetics Dampen the Hydrogen Evolution Reaction to Maximize Zinc Anode Stability
Authors: Roy Kingshuk , Rana Ashutosh , Ghosh Tushar K , Heil Joseph N , Roy Sayan , Vannoy Kathryn J , Tackett Brian M. , Chen Ming , Dick Jeffrey E.
Published: February 2024

Aqueous zinc metal batteries (AZMB) are emerging as a promising alternative to the prevailing existing Lithium‐ion battery technology. However, the development of AZMBs is hindered due to challenges including dendrite formation, hydrogen evolution reaction (HER), and ZnO passivation on the anode. Here, a tetraalkylsulfonamide (TAS) additive for suppressing HER, dendrite formation, and enhancing cyclability is rationally designed. Only 1 mm TAS is found that can effectively displace water molecules from the Zn2+ solvation shell, thereby altering the solvation matrix of Zn2+ and disrupting the hydrogen bond network of free water, as demonstrated through 67 Zn and 1H nuclear magnetic resonance spectroscopy, high‐resolution mass spectrometry (HRMS), and density functional theory (DFT) studies. Voltammetry synchronized with in situ monitoring of the electrode surface reveals suppressed dendritic growth and HER in the presence of TAS. Electrochemical mass spectrometry (ECMS) captures real‐time HER suppression during Zn electrodeposition, revealing the ability of TAS to suppress the HER by an order of magnitude. A ≈25‐fold cycle life improvement from ≈100 h to over 2500 h in coin cells cycled in the presence of TAS. Furthermore, by suppressing passivation product formation, it is demonstrated that strategy robustly maximizes the stability of Zn metal anodes.
Direct Recycling of β‐Li3PS4‐Based All‐Solid‐State Li‐Ion Batteries: Interactions of Electrode Materials and Electrolyte in a Dissolution‐Based Separation Process
Authors: Wissel Kerstin , Haben Aaron , Küster Kathrin , Starke Ulrich , Kautenburger Ralf , Ensinger Wolfgang , Clemens Oliver
Published: February 2024

All‐solid‐state batteries (ASSB) are currently developed at high pace and show a strong potential for market introduction within the next years. Though their performance has improved considerably over the last years, investigation of their sustainability and the development of suitable recycling strategies have received less attention. However, their potential for efficient circular processes must be accessed comprehensively. In this article, the separation of the solid electrolyte β‐Li3PS4 from different lithium transition metal oxide electrode materials (LiCoO2, LiMn2O4, LiNi0.8Mn0.1Co0.1O2, LiFePO4, LiNi0.8Co0.15Al0.05O2, and Li4Ti5O12) are investigated via an approach based on the dissolution and subsequent precipitation of the thiophosphate using N‐methylformamide as solvent. A combination of X‐ray diffraction, scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, inductively coupled plasma mass spectrometry, iodometric titration, and X‐ray photoelectron spectroscopy as well as electrochemical impedance spectroscopy and electrochemical characterization is used to characterize the electrolyte and electrode materials before and after separation. Herein, it is found that the presence of electrode materials in the dissolution process can lead to significant chemical reactions. These interactions can (but most not) lead to strong alteration of the electrochemical characteristics of the individual compounds. Thus, it is shown that an efficient recovery of materials likely depends on the precise material combination within an ASSB.
Hydrodynamics, mass transfer, and hydrogenation performance of a HiGee‐aided fixed bed reactor
Authors: Liao Hai‐Long , Jiang Lan , Wang Li‐Hua , Luo Yong , Tan Qing‐Feng , Ma Shou‐Tao , Chen Jian‐Feng
Published: February 2024

Microbubble shows great potential for hydrogenation reaction in fixed bed reactors (FBRs). However, the lack of understanding of the hydrodynamic behaviors of microbubble swarm in FBR limits the reactor design. In this work, a pilot‐scale HiGee‐aided fixed bed reactor (HFBR), including a HiGee microbubble generator (HMG) and a catalyst bed, has been developed and then applied for poly alpha olefin 4 (PAO 4) hydrogenation. An empirical correlation of Sauter mean diameter (d32) of microbubbles at the inlet and outlet of catalyst bed was established. The gas holdup (φb) of catalyst bed with HMG was 5–10 times higher than that without HMG. Based on d32 and φb, the effective interfacial area in HFBR was calculated as 2000–6000 m2/m3. Compared with static mixer‐aided fixed bed reactor, the aromatic content of PAO 4 hydrogenated in the HFBR was 56%–69% lower, which shows bright future for industrial application.
Clinical outcomes of hypomethylating agents plus Venetoclax as frontline treatment in patients 75 years and older with acute myeloid leukemia: Real‐world data from eight US academic centers
Authors: Abaza Yasmin , Winer Eric S. , Murthy Guru Subramanian Guru , Shallis Rory M. , Matthews Andrew H. , Badar Talha , Geramita Emily M. , Kota Vamsi K. , Swaroop Alok , Doukas Peter , Bradshaw Danielle , Helenowski Irene B. , Liu Yingzhe , Zhang Hui , Im Annie , Litzow Mark R. , Perl Alexander E. , Atallah Ehab , Altman Jessica K.
Published: February 2024

Venetoclax (VEN) combined with hypomethylating agents (HMAs) is the standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) unfit for intensive chemotherapy. To date, real‐world data published on HMAs plus VEN have been either single‐center studies or using community‐based electronic databases with limited details on mutational landscape, tolerability, and treatment patterns in elderly patients. Therefore, we conducted a multicenter retrospective study to assess the real‐world experience of 204 elderly patients (≥75 years) with newly diagnosed AML treated with HMAs plus VEN from eight academic centers in the United States. Overall, 64 patients achieved complete remission (CR; 38%) and 43 CR with incomplete count recovery (CRi; 26%) for a CR/CRi rate of 64%, with a median duration of response of 14.2 months (95% CI: 9.43, 22.1). Among responders, 63 patients relapsed (59%) with median overall survival (OS) after relapse of 3.4 months (95% CI, 2.4, 6.7). Median OS for the entire population was 9.5 months (95% CI, 7.85–13.5), with OS significantly worse among patients with TP53‐mutated AML (2.5 months) and improved in patients harboring NPM1, IDH1, and IDH2 mutations (13.5, 18.3, and 21.1 months, respectively). The 30‐day and 60‐day mortality rates were 9% and 19%, respectively. In conclusion, HMAs plus VEN yielded high response rates in elderly patients with newly diagnosed AML. The median OS was inferior to that reported in the VIALE‐A trial. Outcomes are dismal after failure of HMAs plus VEN, representing an area of urgent unmet clinical need.
Excess prenatal loss and respiratory illnesses of infant macaques living outdoors and exposed to wildfire smoke
Authors: Berns Kathryn , Haertel Andrew J.
Published: February 2024

Global climate change has transformed predictions of fire seasons in the near future, and record‐breaking wildfire events have had catastrophic consequences in recent years. In September 2020, multiple wildfires subjected Oregon to hazardous air quality for several days. In this retrospective cohort study, we aimed to examine prenatal loss, morbidity, and mortality of rhesus (Macaca mulatta) and Japanese macaques (Macaca fuscata) exposed to poor air quality from the nearby wildfires. Detailed medical records from 2014 to 2020 of 580 macaques housed outdoors at a research facility in Beaverton, Oregon were used to evaluate the association between these health outcomes and wildfire smoke exposure. Logistic regression models estimated excess prenatal loss, hospitalization rates, respiratory problems, and mortality during and following the wildfire event, and Kruskal–Wallis statistics were used to determine if infant growth was affected by wildfire smoke exposure. Risk of pregnancy loss (relative risk = 4.1; p < 0.001) and odds of diagnosis with a respiratory problem (odds ratio = 4.47; p = 0.003) were higher in exposed infant macaques compared to nonexposed infants. Infant growth was not affected by poor air quality exposure. Our findings suggest wildfire smoke exposure poses a risk to the health of infants and pregnant individuals and should be monitored more closely in the future.
Decoding chronic rhinosinusitis: A metabolomics‐based approach
Authors: Gong Xinru , Fu Yijie , Zhou Lei , Wei Aiming , Pan Chongsheng , Zhu Tianmin , Li Hui
Published: February 2024

Background

Chronic rhinosinusitis (CRS) is a common and intractable disease in otorhinolaryngology, laying a heavy burden on healthcare systems. The worldwide researchers are making efforts to find solutions to this disease. Metabolomics has recently gained more and more traction, and might become a promising tool to unravel the complexity of CRS. This paper provides an overview of current studies on the metabolomics of various CRS subtypes.

Methods

We conducted a comprehensive literature search in PubMed, Web of Science, EMBASE, Google Scholar, and Cochrane Library, up to May 25, 2023. Search strategies incorporated key terms such as “chronic rhinosinusitis” and “metabolomics” with relevant synonyms and MeSH terms. Titles and abstracts of 86 screened articles were assessed for relevance to CRS and metabolomics. Methodological robustness, data reliability, and relevance were considered for shortlisted articles.

Results

After the refined process, a total of 26 articles were included in this study and sorted out by research themes, methodology and pivotal discoveries. These included studies identified the metabolic pathways and markers related to the pathophysiology in each subtype of CRS.

Conclusions

Metabolomics helps to shed light on the complexity of CRS. The mentioned findings highlight the importance of specific metabolic pathways and markers in understanding the pathophysiology of CRS. Despite that, challenges and future directions in metabolomics research for CRS would be worth being further explored.
Orthogonal sp3‐Ge/B Bimetallic Modules: Enantioselective Construction and Enantiospecific Cross‐Coupling
Authors: Xu Meng‐Yu , Jiang Wei‐Tao , Xia Ming‐Zhi , An Zi‐Long , Xie Xiu‐Ying , Xiao Bin
Published: February 2024

In this study, a series of enantioenriched sp3‐Ge/B bimetallic modules were successfully synthesized via an enantioselective copper‐catalyzed hydroboration of carbagermatrane (Ge)‐containing alkenes. Orthogonal cross‐coupling selectivity under different Pd‐catalyzed conditions was achieved in an enantiospecific manner. Notably, the chiral secondary Ge exhibited a remarkable transmetallation ability prior to primary or secondary Bpin. The effectiveness of this Ge/B bimetallic strategy was further demonstrated through the development of new functional small molecules with Aggregation‐Induced Emission (AIE) and Circularly Polarized Luminescence (CPL) performance. This represents the first successful example of synthesis of enantioenriched alkylgermanium reagents that permit enantiospecific cross‐coupling reactions.
Ultrafast Biomimetic Oxidative Folding of Cysteine‐rich Peptides and Microproteins in Organic Solvents
Authors: Kam Antony , Loo Shining , Qiu Yibo , Liu Chuan‐Fa , Tam James P.
Published: February 2024

Disulfides in peptides and proteins are essential for maintaining a properly folded structure. Their oxidative folding is invariably performed in an aqueous‐buffered solution. However, this process is often slow and can lead to misfolded products. Here, we report a novel concept and strategy that is bio‐inspired to mimic protein disulfide isomerase (PDI) by accelerating disulfide exchange rates many thousand‐fold. The proposed strategy termed organic oxidative folding is performed under organic solvents to yield correctly folded cysteine‐rich microproteins instantaneously without observable misfolded or dead‐end products. Compared to conventional aqueous oxidative folding strategies, enormously large rate accelerations up to 113,200‐fold were observed. The feasibility and generality of the organic oxidative folding strategy was successfully demonstrated on 15 cysteine‐rich microproteins of different hydrophobicity, lengths (14 to 58 residues), and numbers of disulfides (2 to 5 disulfides), producing the native products in a second and in high yield.
Where do the Fluorine Atoms Go in Inorganic‐Oxide Fluorinations? A Fluorooxoborate Illustration under Terahertz Light
Authors: Shen Chunjie , Zhang Feng , Sasaki Tetsuo , Eerdun Chaolu , Hayashi Michitoshi , Wang Houng‐wei , Tominaga Keisuke , Mutailipu Miriding , Pan Shilie
Published: February 2024

The substitution of fluorine atoms for oxygen atoms/hydroxyl groups has emerged as a promising strategy to enhance the physical and chemical properties of oxides/hydroxides in fluorine chemistry. However, distinguishing fluorine from oxygen/hydroxyl in the reaction products poses a significant challenge in existing characterization methods. In this study, we illustrate that terahertz (THz) spectroscopy provides a powerful tool for addressing this challenge. To this end, we investigated two fluorination reactions of boric acid, utilizing MHF2 (M=Na, C(NH2)3) as fluorine reagents. Through an interplay between THz spectroscopy and solid‐state density functional theory, we have conclusively demonstrated that fluorine atoms exclusively bind with the sp3‐boron but not with the sp2‐boron in the reaction products of Na[B(OH)3][B3O3F2(OH)2] (NaBOFH) and [C(NH2)3]2B3O3F4OH (GBF2). Based on this evidence, we have proposed a reaction pathway for the fluorinations under investigation, a process previously hindered due to structural ambiguity. This work represents a step forward in gaining a deeper understanding of the precise structures and reaction mechanisms involved in the fluorination of oxides/hydroxides, illuminated by the insights provided by THz spectroscopy.
Electrokinetic Analyses Uncover the Rate‐Determining Step of Biomass‐Derived Monosaccharide Electroreduction on Copper
Authors: Ma Guoquan , Al‐Mahayni Hasan , Jiang Na , Song Dandan , Qiao Bo , Xu Zheng , Seifitokaldani Ali , Zhao Suling , Liang Zhiqin
Published: February 2024

Electrochemical biomass conversion holds promise to upcycle carbon sources and produce valuable products while reducing greenhouse gas emissions. To this end, deep insight into the interfacial mechanism is essential for the rational design of an efficient electrocatalytic route, which is still an area of active research and development. Herein, we report the reduction of dihydroxyacetone (DHA)—the simplest monosaccharide derived from glycerol feedstock—to acetol, the vital chemical intermediate in industries, with faradaic efficiency of 85±5 % on a polycrystalline Cu electrode. DHA reduction follows preceding dehydration by coordination with the carbonyl and hydroxyl groups and the subsequent hydrogenation. The electrokinetic profile indicates that the rate‐determining step (RDS) includes a proton‐coupled electron transfer (PCET) to the dehydrated intermediate, revealed by coverage‐dependent Tafel slope and isotopic labeling experiments. An approximate zero‐order dependence of H+ suggests that water acts as the proton donor for the interfacial PCET process. Leveraging these insights, we formulate microkinetic models to illustrate its origin that Eley–Rideal (E−R) dominates over Langmuir–Hinshelwood (L−H) in governing Cu‐mediated DHA reduction, offering rational guidance that increasing the concentration of the adsorbed reactant alone would be sufficient to promote the activity in designing practical catalysts.
Evaluating high oleic soybean oil oleogels as shortening replacements: Impact on cookie dough, cookie attributes, and oxidative stability
Authors: Zhao Muxin , Rao Jiajia , Chen Bingcan
Published: February 2024

In this study, we explored the potential of oleogels to serve as a substitute for traditional shortening throughout the entire cookie production process. Specifically, oleogel was prepared using expeller‐pressed high oleic soybean oil (EPHOSO) with 10 wt% of either rice bran wax (RBX) or monoacylglycerol (MAG) to replace shortening in cookie making. Rapid Visco Analyzer and Farinograph were used to thoroughly assess the impact of replacing shortening with oleogels on the qualities of cookie dough. The results demonstrated the efficacy of MAG oleogel in replicating the attributes of traditional shortening in cookie doughs, in terms of water absorption, dough consistency, and dough stability. The overall quality of cookies prepared with oleogels was comparable to the ones prepared with shortening. Additionally, the oxidative stability indicated the remarkable advantage of EPHOSO‐based oleogels, which displayed an elevated resistance to oxidative processes compared to its liquid form. Furthermore, cookies prepared with MAG oleogel exhibited prolonged oxidative stability than those prepared with shortening. Overall, the results underscore the potential of EPHOSO oleogels, particularly those incorporated with MAG, could enhance the oxidative stability of cookies without diminishing the physicochemical qualities of the end product.
Global terminal sliding‐mode control for the synchronization problem of uncertain bilateral teleoperation system with time‐varying delays
Authors: Ounissi Asma , Boukattaya Mohamed , Mezghani Ben Romdhane Neila
Published: February 2024

In this paper, an adaptive global terminal sliding‐mode control is developed for a nonlinear bilateral teleoperation system with time‐varying delays, external disturbances, and uncertainties. By selecting a time‐varying sliding‐mode manifold, a finite‐time sliding‐mode control algorithm is proposed to guarantee the suppression of the reaching phase associated with the conventional sliding‐mode control. This implies that the robustness is guaranteed throughout to entire response of the system. Meanwhile, the chattering phenomenon and the energy consumption are significantly reduced. Furthermore, in order to enhance the tracking performance in practical situations, adaptive tuning laws are developed to estimate the unknown upper bounds of the lumped uncertainties. Hence, the proposed approach has several merits, namely, fast response, accurate synchronization, and strong robustness with respect to large uncertainties and disturbances. The stability of the system in closed‐loop and the boundedness on the internal dynamics are proved by Lyapunov stability theory. Illustrative simulations were conducted to show the effectiveness of the proposed controller.
Disturbance observer based control for passive multi‐actuator systems with aggregation and distribution
Authors: Nguyen Binh Minh
Published: February 2024

This paper presents a disturbance observer‐based controller for a class of multi‐actuator systems that possess passivity properties. By distributing the input and aggregating the output using the same vectors, the original plant is transformed into an aggregation‐and‐distribution plant (ADP), which is also passive. Based on the ADP, this paper derives the conditions for the controller to sufficiently ensure that the overall system has a finite L2‐gain. The conditions can be checked via the passivity notation of several transfer functions. It is not required to establish the overall system's dynamical equation, thereby alleviating the design burden. The additional objective can be attained by performing an optimization on the aggregation/distribution vectors. Several practical applications are introduced as motivating examples, and the effectiveness of the proposed method is demonstrated by the integration of motion control and energy management for electric vehicles.
Circular bioeconomy ecosystems: Hydroxyapatite from fish waste at Rio de Janeiro
Authors: Xavier Bárbara Gomes , da Silva Luísa Vieira , Alves Flávia Chaves , Teixeira Leonardo Vieira , Santos Victória Emília Neves
Published: February 2024

The transition to a low‐carbon economy endangered the revenues of many oil‐dependent regions. This is the case in Rio de Janeiro state, Brazil, which has become highly dependent on oil and gas royalties since the 1970s. At the same time, the circular blue bioeconomy has emerged as a pathway for environmentally sound socioeconomic development. In such a context, a biological resource in many oil‐dependent regions is fish processing residue, from which high added‐value compounds can be obtained, such as collagen, hydroxyapatite, gelatin, lipids, enzymes, hydrolysates, and bioactive peptides. The present study aims to understand the potential for a future fish waste hydroxyapatite (FHAp) market in the state of Rio de Janeiro (SRJ). The methodological approach integrates technology roadmapping with market and innovation ecosystem assessment. We found that the main techniques for obtaining FHAp were chemical hydrolysis and calcination, and the most innovative and value‐added applications were biomaterial for tissue regeneration (BTR) and physical sunblock (PS). The mapping of SRJ companies showed that the state has qualified players in cosmetic and biomedical industries that could develop innovations in BTR and PS made of FHAp. However, the mapping also showed a gap in the FHAp extraction stage, which is essential for the value chain. To find and encourage players to compound this innovation ecosystem, the public power can therefore act as an articulator, providing financial incentives and creating infrastructural conditions, such as a waste pretreatment plant next to the state fishing pole.
Ameliorating diabetes‐induced testicular dysfunction by modulating PKC/Nrf2/Bcl‐2 signaling: Protective role of sulbutiamine
Authors: Abdelmonem Maha , Ali Shimaa O. , Al‐Mokaddem Asmaa K. , Ghaiad Heba R.
Published: February 2024

The prevalence of testicular dysfunction is increasing as it is a common diabetes mellites (DM) complication. The objective of this study is to explore the potential protective effect of sulbutiamine against testicular hypofunction associated with streptozotocin (STZ)‐induced DM in rats. Sulbutiamine was administered orally (60 mg/kg) to male Wistar rats for 8 weeks starting 72 h after a single injection of STZ (45 mg/kg, i.p.). Blood glucose level (BGL), serum testosterone level, sperm number, and motility were determined. Testicular tissue was examined histopathologically, and the Johnson score was evaluated. Levels of malondialdehyde (MDA), protein kinase C (PKC), nuclear factor erythroid‐derived 2‐like 2 (Nrf2), and proliferating cell nuclear antigen (PCNA) were measured. Apoptosis was evaluated by immunohistochemical determination of B‐cell lymphoma protein 2 (Bcl‐2), Bcl‐2 associated X‐protein (Bax), and caspase‐3. Sulbutiamine administration managed to reduce BGL and boost testicular function as manifested by increased testicular weight, testosterone level, sperm number, and motility compared to the STZ group. Additionally, histopathological examination revealed an improved histological picture and Johnson score of testicular tissue after sulbutiamine treatment. Sulbutiamine administration reduced testicular PKC, MDA, and PCNA levels and increased Nrf2 compared to the untreated group. Moreover, sulbutiamine treatment suppressed apoptosis triggered by STZ as evidenced by elevated Bcl‐2, decreased Bax and reduced caspase‐3. The present work revealed for the first time a promising protective role of sulbutiamine against STZ‐induced testicular dysfunction which may add to the clinical utility of sulbutiamine. The underlying mechanisms involve reducing BGL and PKC, activating Nrf2 and inhibiting apoptosis.
Antibacterial Sesquiterpene Lactones from Kaunia lasiophthalma
Authors: Marín Edith M. , Reyes María G. , Audisio Marcela C. , Nicotra Viviana E. , Uriburu María L.
Published: February 2024

Phytochemical study of the species Kaunia lasiophthalma enabled the isolation of three undescribed and three known guaianolide‐type sesquiterpene lactones, and one new benzofuran. The bioguided fractionation methodology was successful in detecting antimicrobial metabolites against Staphylococcus aureus strains and permitted the description of undescribed guaianolide‐type sesquiterpene lactones with substitution patterns matching all those described in the Oxylobinae subtribe.
To flip or not: Case series of coronary angioplasty in patients with right‐sided heart
Authors: Kelley Brian P. , Glasco Shanice , Sang Charlie J. , Yoo Bianca , Yeung Michael , Zhang Jiandong
Published: February 2024

Coronary angioplasty in patients with a right‐sided heart may be difficult due to challenges in engaging the coronary arteries, interpreting angiogram, and further delivering intracoronary therapies. We present our experience of percutaneous coronary intervention in two cases and propose a practical algorithm to approach cardiac catheterization in these patients.
Pregnancy and lactation‐related osteoporosis in a 22‐year‐old‐woman
Authors: Ghassa Ali , Hodifa Yara , Falhout Qais
Published: February 2024

Key Clinical Message

Any pregnant or lactating woman with severe constant back pain, PLO must be kept in mind due to its effect on the quality of life of the mother and her child.

A 22‐year‐old woman, who delivered her first child 5 months ago and is now breastfeeding her baby, presented with mid‐back pain. After investigations, including laboratory tests, X‐rays, and bone density measurements, the diagnosis was PLO. The patient is being treated with calcium, vitamin D, and alendronate besides discontinuation of lactation.
Access to a peri‐Annulated Aluminium Compound via C−H Bond Activation by a Cyclic Bis‐Aluminylene
Authors: Merschel Arne , Vishnevskiy Yury V. , Neumann Beate , Stammler Hans‐Georg , Ghadwal Rajendra S.
Published: February 2024

Carbocyclic aluminium halides [(ADC)AlX2]2 (2‐X) (X=F, Cl, and I) based on an anionic dicarbene (ADC=PhC{N(Dipp)C}2, Dipp = 2,6‐iPr2C6H3) framework are prepared as crystalline solids by dehydrohalogenations of the alane [(ADC)AlH2]2 (1). KC8 reduction of 2‐I affords the peri‐annulated Al(III) compound [(ADCH)AlH]2 (4) (ADCH=PhC{N(Dipp)C2(DippH)N}, DippH=2‐iPr,6‐(Me2C)C6H3)) as a colorless crystalline solid in 76 % yield. The formation of 4 suggests intramolecular insertion of the putative bis‐aluminylene species [(ADC)Al]2 (3) into the methine C−H bond of HCMe2 group. Calculations predict singlet ground state for 3, while the conversion of 3 into 4 is thermodynamically favored by 61 kcal/mol. Compounds 2‐F, 2‐Cl, 2‐I, and 4 have been characterized by NMR spectroscopy and their solid‐state molecular structures have been established by single crystal X‐ray diffraction.
Synthesis of Diverse Oxetane Amino Acids via Visible‐Light‐Induced Photocatalytic Decarboxylative Giese‐Type Reaction
Authors: Shi Haoliang , Wan Yi , Zhang Yongqiang
Published: February 2024

Comprehensive Summary

The divergent synthesis of versatile 3,3′‐disubstituted oxetane amino acids by utilizing visible‐light‐induced photocatalytic decarboxylative Giese‐type reaction has been demonstrated. 3‐Methyleneoxetane‐derived substrates are readily available in a single‐step and highly reactive as radical acceptors, allowing the production of versatile oxetane γ‐ and α‐amino acids in high yields. A distinct ring strain release‐driven radical addition mechanism was preliminarily revealed. The preparative power was further highlighted by the application in the synthesis of oxetane‐containing dipeptides and azetidine amino acids, as well as the transformation of the product into novel oxetane‐containing spiro‐heterocycle pharmacophore.
Safety, Pharmacokinetics, and Pharmacodynamics of Etrasimod: Single and Multiple Ascending Dose Studies in Healthy Adults
Authors: Lee Caroline A. , Schreiber Stefan , Bressler Brian , Adams John W. , Oh Dooman Alexander , Tang Yong Q. , Zhang Jinkun , Komori Heather Kiyomi , Grundy John S.
Published: February 2024

Etrasimod is an investigational, once‐daily, oral, selective sphingosine 1‐phosphate receptor 1,4,5 modulator in development for immune‐mediated inflammatory diseases (IMIDs). Here, we report the human safety, pharmacokinetics, and pharmacodynamics of etrasimod obtained from both a single ascending dose (SAD; 0.1‐5 mg) study and a multiple ascending dose (MAD; 0.35‐3 mg once daily) study. Overall, 99 healthy volunteers (SAD n = 40, MAD n = 59) completed the 2 studies. Evaluated single and multiple doses were well tolerated up to 3 mg without severe adverse events (AEs). Gastrointestinal disorders were the most common etrasimod‐related AEs. Over the evaluated single‐ and multiple‐dose ranges, dose‐proportional and marginally greater‐than‐dose‐proportional etrasimod plasma exposure were observed, respectively. At steady state, etrasimod oral clearance and half‐life mean values ranged from 1.0 to 1.2 L/h and 29.7 to 36.4 hours, respectively. Dose‐dependent total peripheral lymphocyte reductions occurred following etrasimod single and multiple dosing. Etrasimod multiple dosing resulted in reductions from baseline in total lymphocyte counts ranging from 41.1% to 68.8% after 21 days. Lymphocyte counts returned to normal range within 7 days following treatment discontinuation. Heart rate lowering from pretreatment baseline on etrasimod dosing was typically mild, with mean reductions seen after the first dose of up to 19.5 bpm (5 mg dose). The favorable safety, pharmacokinetic, and pharmacodynamic properties of etrasimod in humans supported its further development and warranted its investigation for treatment of IMIDs.
A Natural Language Processing Approach Towards Harmonized Communication of Uncertainties Identified During the European Medicine Authorization Process
Authors: Verweij Stefan , Haverhoek Vincent , Bergman Erik , Westman Gabriel , Bloem Lourens T.
Published: February 2024

Within the European Union, the European Medicines Agency's (EMA's) European Public Assessment Report (EPAR) is an important source of information for healthcare professionals and patients that allows them to understand important risks and uncertainties associated with the use of a medicine. However, the EPAR sections describing such important uncertainties can differ substantially in wording, length, and detail, thereby potentially limiting understanding. In this study, we therefore present a natural language processing approach to cluster sentences extracted from the sections on uncertainties in EPARs of centrally authorized medicines, as a steppingstone to harmonization of text describing uncertainties. We used a BERT language model together with dimensionality reduction (Uniform Manifold Approximation and Projection (UMAP)) and clustering (Density‐Based Spatial Clustering of Applications with Noise (DBSCAN)) to identify semantic similarities between sentences. Clusters were labeled according to an overarching topic by reviewing the semantically similar sentences. Each cluster was also characterized according to medicine‐related characteristics, such as efficacy or side effects. In total, 1,648 medicines were included in this study. For 573 of these medicines (authorized July 27, 2010 to December 31, 2022), we identified an EPAR that described a complete regulatory dossier and contained sections on uncertainties. Of these, 553 EPARs could be attributed to unique active substance‐indication combinations. In these 553 EPARs, we identified 13,105 sentences in sections on uncertainties, leading to 26 clusters of which 2 were labeled as noise. The clusters and associated topics provided in this article can be used by regulators and medicine developers as a steppingstone toward a unified way of communicating uncertainties identified during the EMA process to the broader public.
Predictive Modeling of Drug‐Related Adverse Events with Real‐World Data: A Case Study of Linezolid Hematologic Outcomes
Authors: Patel Anu , Doernberg Sarah B. , Zack Travis , Butte Atul J. , Radtke Kendra K.
Published: February 2024

Electronic health records (EHRs) provide meaningful knowledge of drug‐related adverse events (AEs) that are not captured in standard drug development and postmarketing surveillance. Using variables obtained from EHR data in the University of California San Francisco de‐identified Clinical Data Warehouse, we aimed to evaluate the potential of machine learning to predict two hematological AEs, thrombocytopenia and anemia, in a cohort of patients treated with linezolid for 3 or more days. Features for model input were extracted at linezolid initiation (index), and outcomes were characterized from index to 14 days post‐treatment. Random forest classification (RFC) was used for AE prediction, and reduced feature models were evaluated using cumulative importance (cImp) for feature selection. Grade 3+ thrombocytopenia and anemia occurred in 31% of 2,171 and 56% of 2,170 evaluable patients, respectively. Of the total 53 features, as few as 7 contributed at least 50% cImp, resulting in prediction accuracies of 70% or higher and area under the receiver operating characteristic curves of 0.886 for grade 3+ thrombocytopenia and 0.759 for grade 3+ anemia. Sensitivity analyses in strictly defined patient subgroups revealed similarly high predictive performance in full and reduced feature models. A logistic regression model with the same 50% cImp features showed similar predictive performance as RFC and good concordance with RFC probability predictions after isotonic calibration, adding interpretability. Collectively, this work demonstrates potential for machine learning prediction of AE risk in real‐world patients using few variables regularly available in EHRs, which may aid in clinical decision making and/or monitoring.
A hybrid mixed‐cells DC‐DC modular multilevel converter with balanced arm energy and DC fault blocking capability for high voltage direct current systems
Authors: Farghly Abdelrahman , Elserougi Ahmed , Abdel‐khalik Ayman , Hamdy Ragi
Published: February 2024

DC‐DC converters play a vital role in the integration of renewable energy sources. Modular multilevel converter (MMC) has emerged as a highly promising option for high‐voltage high‐power applications, for DC‐AC and DC‐DC conversion, thanks to its distinctive characteristics. An inherent limitation of using traditional MMC in DC‐DC conversion is the occurrence of arm energy drift, leading to imbalanced voltages across capacitors of submodules (SMs). Many approaches have been presented in the literature to address the energy drift issue during DC‐DC conversion process. In this paper, a novel bidirectional hybrid modular multilevel DC‐DC converter with balanced arm energy has been proposed. The proposed converter consists of one high‐voltage valve and two legs. Each leg is equipped with half‐bridge submodules (HB‐SMs) in the upper arm and full‐bridge submodules (FB‐SMs) in the lower arm. The proposed architecture enables the parallel connection between series‐connected capacitors of the upper arm and series‐connected capacitors of the lower arm during the equalization period. The parallel connectivity enables the energy transfer between the upper and lower arms in the same leg, hence preventing energy drift issues. A detailed illustration of converter operational concept, mathematical analysis, design, and efficiency estimation are presented. The presented simulation and experimental results show the bidirectional power flow ability and the promising behavior of the proposed converter during normal operating conditions with balanced arm energy. Finally, a comparison between the proposed converter and other existing topologies has been made to show the superiority of the proposed converter over the other alternatives. The proposed converter has a lower count of insulated gate bipolar transistors (IGBTs) and eliminates the usage of isolating transformers when compared to the energy equalization modules approach. In addition, unlike the other alternatives, the proposed converter has a DC fault blocking capability.
Phase shift control of dual active bridge DC‐DC converter based on feedforward compensation and transient optimization strategy
Authors: Luo Lei , Liu Yitao , Yin Jian , YunWang  , Pan Xuewei
Published: February 2024

In the context of the dual active bridge (DAB) bidirectional DC‐DC converter using the traditional dual‐phase‐shift (DPS) control method, a transient DC bias occurs during power co‐direction and commutation conversion. This bias negatively impacts the converter's transient performance and can lead to harsh effects, such as hard switching problems, resulting in power loss and excessive current stress. In a closed‐loop control system, poor transient response may destroy the stability of the converter. In this paper, the transient‐optimized‐dual‐phase‐shift (TODPS) control strategy is proposed to eliminate the transient DC bias and to maintain soft switching during transient states. It reduces power loss, eliminates excessive current stress, and allows for smooth transitions between single‐phase‐shift (SPS) and DPS control strategies without introducing DC bias. A closed‐loop control system based on TODPS control is established with feed‐forward compensation to adjust the primary‐side current and modify transmission power. This adjustment enhances the transient performance of the DAB converter. The proposed strategy is versatile and applicable to various power conversion scenarios involving DAB converters. It enables quick switching of the magnitude and direction of the primary‐side current during transient states, resulting in a smooth transient effect without noticeable overshoot or oscillation. The experiment results verify the effectiveness of the proposed transient optimization strategy.
Variation in the contribution of macroinvertebrates to wood decomposition as it progresses
Authors: Taylor Melanie K. , Ulyshen Michael D. , Horn Scott , Poole Emilee M. , Callaham Mac A.
Published: February 2024

Although necromass decay rates are limited by the slowest portions to decompose, most decomposition studies examine only the earliest stage of decay. As such, these studies run the risk of yielding misleading results regarding the relative contributions of different decomposers. For example, the contributions of macroinvertebrates to wood decomposition remain mostly unknown beyond the first 50% of mass lost, despite drastic changes in substrate conditions over time. We sought to clarify how the macroinvertebrate contribution to decay changes over the course of wood decomposition in the Southeastern United States—a region with a long history of wood decomposition research. To this end, we (1) compiled data from published studies comparing wood decay with and without macroinvertebrates; and (2) conducted a field study assessing wood mass loss, with and without macroinvertebrate access, at three sites across the region over four years. With these combined data, we analyzed macroinvertebrate contribution as decay progressed, revealing a quadratic relationship, wherein macroinvertebrate contribution increased early in decomposition and then began to decline as decay progressed. Strong local site effects, particularly the abundance and activity of termites, determine the time required for wood to reach this point of mass loss.