bluuebunny/crossref_metadata_2025 huggingface dataset:
CD19 Chimeric Antigen Receptor T Cell Treatment: Unraveling the Role of B Cells in Systemic Lupus Erythematosus
Authors: Taubmann Jule , Müller Fabian , Yalcin Mutlu Melek , Völkl Simon , Aigner Michael , Bozec Aline , Mackensen Andreas , Grieshaber‐Bouyer Ricardo , Schett Georg
Published: December 2023

B cell generation of autoantibodies is a crucial step in the pathogenesis of systemic lupus erythematosus (SLE). After their differentiation in the bone marrow, B cells populate the secondary lymphatic organs, where they undergo further maturation leading to the development of memory B cells as well as antibody‐producing plasmablasts and plasma cells. Targeting B cells is an important strategy to treat autoimmune diseases such as SLE, in which B cell tolerance is disturbed and autoimmune B cells and autoantibodies emerge. This review discusses the functional aspects of antibody‐ and cell‐based B cell–depleting therapy in SLE. It thereby particularly focuses on lessons learned from chimeric antigen receptor (CAR) T cell treatment on the role of B cells in SLE for understanding B cell pathology in SLE. CAR T cells model a deep B cell depletion and thereby allow understanding the role of aberrant B cell activation in the pathogenesis of SLE. Furthermore, the effects of B cell depletion on autoantibody production can be better described, ie, explaining the concept of different cellular sources of (auto‐) antibodies in the form of short‐lived plasmablasts and long‐lived plasma cells, which differ in their susceptibility to B cell depletion and require different targeted therapeutic approaches. Finally, the safety of deep B cell depletion in autoimmune disease is discussed.
Evaluation of mitochondrial stress following ultraviolet radiation and 5G radiofrequency field exposure in human skin cells
Authors: Patrignoni Lorenza , Hurtier Annabelle , Orlacchio Rosa , Joushomme Alexandre , Poulletier de Gannes Florence , Lévêque Philippe , Arnaud‐Cormos Delia , Revzani Hamid Reza , Mahfouf Walid , Garenne André , Percherancier Yann , Lagroye Isabelle
Published: December 2023

Whether human cells are impacted by environmental electromagnetic fields (EMF) is still a matter of debate. With the deployment of the fifth generation (5G) of mobile communication technologies, the carrier frequency is increasing and the human skin becomes the main biological target. Here, we evaluated the impact of 5G‐modulated 3.5 GHz radiofrequency (RF) EMF on mitochondrial stress in human fibroblasts and keratinocytes that were exposed for 24 h at specific absorption rate of 0.25, 1, and 4 W/kg. We assessed cell viability, mitochondrial reactive oxygen species (ROS) production, and membrane polarization. Knowing that human skin is the main target of environmental ultraviolet (UV), using the same read‐out, we investigated whether subsequent exposure to 5G signal could alter the capacity of UV‐B to damage skin cells. We found a statistically significant reduction in mitochondrial ROS concentration in fibroblasts exposed to 5G signal at 1 W/kg. On the contrary, the RF exposure slightly but statistically significantly enhanced the effects of UV‐B radiation specifically in keratinocytes at 0.25 and 1 W/kg. No effect was found on mitochondrial membrane potential or apoptosis in any cell types or exposure conditions suggesting that the type and amplitude of the observed effects are very punctual.
Combined in vitro/in silico approaches, molecular dynamics simulations and safety assessment of the multifunctional properties of thymol and carvacrol: A comparative insight
Authors: Akermi Sarra , Smaoui Slim , Chaari Moufida , Elhadef Khaoula , Gentile Rocco , Hait Milan , Roymahapatra Gourisankar , Mellouli Lotfi
Published: December 2023

Bioactive compounds derived from medicinal plants have acquired immense attentiveness in drug discovery and development. The present study investigated in vitro and predicted in silico the antibacterial, antifungal, and antiviral properties of thymol and carvacrol, and assessed their safety. The performed microbiological assays against Pseudomonas aeruginosa, Escherichia coli, Salmonella enterica Typhimurium revealed that the minimal inhibitory concentration values ranged from (0.078 to 0.312 mg/mL) and the minimal fungicidal concentration against Candida albicans was 0.625 mg/mL. Molecular docking simulations, stipulated that these compounds could inhibit bacterial replication and transcription functions by targeting DNA and RNA polymerases receptors with docking scores varying between (−5.1 to −6.9 kcal/mol). Studied hydroxylated monoterpenes could hinder C. albicans growth by impeding lanosterol 14α‐demethylase enzyme and showed a (ΔG=−6.2 and −6.3 kcal/mol). Computational studies revealed that thymol and carvacrol could target the SARS‐Cov‐2 spike protein of the Omicron variant RBD domain. Molecular dynamics simulations disclosed that these compounds have a stable dynamic behavior over 100 ns as compared to remdesivir. Chemo‐computational toxicity prediction using Protox II webserver indicated that thymol and carvacrol could be safely and effectively used as drug candidates to tackle bacterial, fungal, and viral infections as compared to chemical medication.
Programmed cell death 4: A novel player in the pathogenesis of polycystic ovary syndrome
Authors: Zarezadeh Reza , Abbasi Khadijeh , Aboutalebi Vand Beilankouhi Elmira , Navali Nazli , Hakimi Parvin , Fattahi Amir , Farzadi Laya
Published: December 2023

Polycystic ovary syndrome (PCOS) is a pathological condition recognized by menstrual cycle irregularities, androgen excess, and polycystic ovarian morphology, affecting a significant proportion of women of childbearing age and accounting for the most prevalent cause of anovulatory sterility. In addition, PCOS is frequently accompanied by metabolic and endocrine disturbances such as obesity, dyslipidemia, insulin resistance, and hyperinsulinemia, indicating the multiplicity of mechanisms implicated in the progression of PCOS. However, the exact pathogenesis of PCOS is yet to be elucidated. Programmed cell death 4 (PDCD4) is a ubiquitously expressed protein that contributes to the regulation of various cellular processes, including gene expression, cell cycle progression, proliferation, and apoptosis. Despite some disparities concerning its exact cellular effects, PDCD4 is generally characterized as a protein that inhibits cell cycle progression and proliferation and instead drives the cell into apoptosis. The apoptosis of granulosa cells (GCs) is speculated to take a major part in the occurrence and progression of PCOS by ceasing antral follicle development and compromising oocyte competence. Given the possible involvement of GC apoptosis in the progression of PCOS, as well as the contribution of PDCD4 to the regulation of cell apoptosis and the development of metabolic diseases, the current review aimed to discuss whether or how PDCD4 can play a role in the pathogenesis of PCOS by affecting GC apoptosis.
Formation of Bridged Disulfide in Epidithiodioxopiperazines
Authors: Fan Jie , Wei Peng‐Lin , Yin Wen‐Bing
Published: December 2023

Epidithiodioxopiperazine (ETP) alkaloids, featuring a 2,5‐diketopiperazine core and transannular disulfide bridge, exhibit a broad spectrum of biological activities. However, the structural complexity has prevented efficient chemical synthesis and further clinical research. In the past few decades, many achievements have been made in the biosynthesis of ETPs. Here, we discuss the biosynthetic progress and summarize them as two comprehensible metabolic principles for better understanding the complex pathways of α, α′‐ and α, β′‐disulfide bridged ETPs. Specifically, we systematically outline the catalytic machineries to install α, α′‐ and α, β′‐disulfide by flavin‐containing oxygenases. This concept would contribute to the medical and industrial applications of ETPs.
KLK10 promotes the progression of KRAS mutant colorectal cancer via PAR1‐PDK1‐AKT signaling pathway
Authors: Wu Kun , Wu Boyu , Yan Kangpeng , Ding Qunhua , Miao Zhiguo
Published: December 2023

Kirsten rat sarcoma virus (KRAS) gene mutation is common in colorectal cancer (CRC) and is often predictive of treatment failure and poor prognosis. To understand the mechanism, we compared the transcriptome of CRC patients with wild‐type and mutant KRAS and found that KRAS mutation is associated with the overexpression of a secreted serine protease, kallikrein‐related peptidase 10 (KLK10). Moreover, using in vitro and in vivo models, we found that KLK10 overexpression favors the rapid growth and liver metastasis of KRAS mutant CRC and can also impair the efficacy of KRAS inhibitors, leading to drug resistance and poor survival. Further functional assays revealed that the oncogenic role of KLK10 is mediated by protease‐activated receptor 1 (PAR1). KLK10 cleaves and activates PAR1, which further activates 3‐phosphoinositide‐dependent kinase 1 (PDK1)‐AKT oncogenic pathway. Notably, suppressing PAR1‐PDK1‐AKT cascade via KLK10 knockdown can effectively inhibit CRC progression and improve the sensitivity to KRAS inhibitor, providing a promising therapeutic strategy. Taken together, our study showed that KLK10 promotes the progression of KRAS mutant CRC via activating PAR1‐PDK1‐AKT signaling pathway. These findings expanded our knowledge of CRC development, especially in the setting of KRAS mutation, and also provided novel targets for clinical intervention.
Comment on “Asymmetric Bistricyclic Aromatic Enes”
Authors: Agranat Israel
Published: December 2023

This Correspondence argues against the use of the adjectives “symmetrical” and “asymmetric” in the recent publication entitled “Fluorenylidene‐Cyclopentadithiophene Based Asymmetric Bistricyclic Aromatic Ene Compounds: Synthesis and Substituents Effects”, by Beibei Xiao, Yongrui Yang, Shengnan Chen, Ye Zou, Xing Chen, Kanglei Liu, Nan Wang, Yali Qiao, and Xiaodong Yin (Chem. Eur. J., 2023, 29, e202301055).[1]
Fe and Cu Intercalations Enhance SERS of MoO3 through Different Mechanistic Pathways
Authors: Wang Hengan , An Guangyu , Xu Song , Xu Qun
Published: December 2023

Surface Enhanced Raman spectroscopy (SERS) is a molecular‐specific analytical technique with various applications. Although electromagnetic (EM) and chemical (CM) mechanisms have been proposed to be the main origins of SERS, exploring highly sensitive SERS substrates with well‐defined mechanistic pathways remains challenging. Since surface and electronic structures of substrates were crucial for SERS activity, zero‐valent transition metals (Fe and Cu) were intercalated into MoO3 to modulate its surface and electronic structures, leading to unexceptional high enhancement factors (1.0×108 and 1.1×1010 for Fe‐MoO3 and Cu‐MoO3, respectively) with decent reproducibility and stability. Interestingly, different mechanistic pathways (CM and EM) were proposed for Fe‐MoO3 and Cu‐MoO3 according to mechanistic investigations. The different mechanisms of Fe‐MoO3 and Cu‐MoO3 were rationalized by the electronic structures of the intercalated Fe(0) and Cu(0), which modulates the surface and electronic structures of Fe‐MoO3 and Cu‐MoO3 to differentiate their SERS mechanisms.
trans‐Cyclooctenes as Scavengers of Bromine Involved in Catalytic Bromination
Authors: Murata Ryuichi , Shitamichi Kenta , Hiramatsu Masatsugu , Matsubara Seijiro , Uraguchi Daisuke , Asano Keisuke
Published: December 2023

Scavengers that capture reactive chemical substances are used to prevent the decomposition of materials. However, in the field of catalysis, the development of scavengers that inhibit background pathways has attracted little attention, although the concept will open up an otherwise inaccessible reaction space. In catalytic bromination, fast non‐catalyzed background reactions disturb the catalytic control of the selectivity, even when using N‐bromoamide reagents, which have a milder reactivity than bromine (Br2). Here, we developed a trans‐cyclooctene (TCO) bearing a 2‐pyridylethyl group to efficiently retard background reactions by capturing Br2 in bromocyclization using N‐bromosuccinimide. The use of less than a stoichiometric amount of the TCO was sufficient to inhibit non‐catalyzed reactions, and mechanistic studies using the TCO revealed that in situ‐generated Br2 provides non‐catalyzed reaction pathways based on a chain mechanism. The TCO is useful as an additive for improving enantioselectivity and regioselectivity in catalytic reactions. Cooperative systems using the TCO with selective catalysts offer an alternative strategy for optimizing catalyst‐controlled selectivity during bromination. Moreover, it also served as an indicator of Br2 involved in catalytic reaction pathways; thus, the TCO was useful as a probe for mechanistic investigations into the involvement of Br2 in bromination reactions of interest.
Effect of pyrolysis temperature and hydrothermal activation on structure, physicochemical, thermal and dye adsorption characteristics of the biocarbons
Authors: Charmas Barbara , Wawrzaszek Barbara , Jedynak Katarzyna
Published: December 2023

In this study, the possibility of using sawdust from mixed woods to obtain biocarbons in the pyrolysis and steam activation using microwave radiation as an energy source was investigated. Biocarbons were characterized based on the results of N2 adsorption, thermogravimetric analysis (TGA), Fourier spectroscopy (ATR‐FTIR), and Raman spectroscopy. Surface characterization was performed by Boehm titration and pHpzc determination. The adsorption capacity of methylene blue (MB) and methyl orange (MO) was studied. It was proved that the pyrolysis temperature and hydrothermal activation increased the biocarbons structural, surface and adsorption parameters of the obtained biocarbons. The amorphous materials of small specific surface area with a significant share of micropores were obtained. The steam activation resulted in significant development of the porous structure (to SBET=729.2 m2/g and Vp=0.36 cm3/g). The presence of functional groups, mainly phenolic ones, and pHpzc values indicating a potential for adsorption applications regarding MO and MB were found. The highest sorption capacity concerning MB (qe=122.8 mg/g) and MO (qe=99.1 mg/g) was observed for the steam‐activated biocarbon BC‐800MW. Using microwave energy hydrothermal activation proved very efficient, resulting in significant surface area and porosity development with a small loss of carbon matter.
Development of a Thermodynamically Favorable Multi‐enzyme Cascade Reaction for Efficient Sustainable Production of ω‐Amino Fatty Acids and α,ω‐Diamines
Authors: Li Ju‐Mou , Shi Kun , Li Ai‐Tao , Zhang Zhi‐Jun , Yu Hui‐Lei , Xu Jian‐He
Published: December 2023

Aliphatic ω‐amino fatty acids (ω‐AFAs) and α,ω‐diamines (α,ω‐DMs) are essential monomers for the production of nylons. Development of a sustainable biosynthesis route for ω‐AFAs and α,ω‐DMs is crucial in addressing the challenges posed by climate change. Herein, we constructed an unprecedented thermodynamically favorable multi‐enzyme cascade (TherFavMEC) for the efficient sustainable biosynthesis of ω‐AFAs and α,ω‐DMs from cheap α,ω‐dicarboxylic acids (α,ω‐DAs). This TherFavMEC was developed by incorporating bioretrosynthesis analysis tools, reaction Gibbs free energy calculations, thermodynamic equilibrium shift strategies and cofactor (NADPH&ATP) regeneration systems. The molar yield of 6‐aminohexanoic acid (6‐ACA) from adipic acid (AA) was 92.3 %, while the molar yield from 6‐ACA to 1,6‐hexanediamine (1,6‐HMD) was 96.1 %, which were significantly higher than those of previously reported routes. Furthermore, the biosynthesis of ω‐AFAs and α,ω‐DMs from 20.0 mM α,ω‐DAs (C6‐C9) was also performed, giving 11.2 mM 1,6‐HMD (56.0 % yield), 14.8 mM 1,7‐heptanediamine (74.0 % yield), 17.4 mM 1,8‐octanediamine (87.0 % yield), and 19.7 mM 1,9‐nonanediamine (98.5 % yield), respectively. The titers of 1,9‐nonanediamine, 1,8‐octanediamine, 1,7‐heptanediamine and 1,6‐HMD were improved by 328‐fold, 1740‐fold, 87‐fold and 3.8‐fold compared to previous work. Therefore, this work holds great potential for the bioproduction of ω‐AFAs and α,ω‐DMs.
A quick demagnetization approach for low torque ripple in three‐phase switched reluctance motor drive system for electric vehicle applications
Authors: Damarla Indira , Mahendran Venmathi , Ganji Ramudu , A Sangari
Published: December 2023

Electric vehicles (EVs) have gained a forward approach for achieving the low carbon economy and green transportation. Switched reluctance (SR) motor‐based propulsion mechanisms have been popularly used for EVs due to the wide speed range capability. The conventional phase current regulation technique does not give the satisfactory reduction of torque ripple in SR motor drive, particularly for automotive applications. To overcome the issue, a frontend boost converter (FEBC) is proposed to realize the quick excitation and demagnetization. Initially, the problems associated with the conventional asymmetric half bridge converter are investigated at various levels of phase current. The various operating modes of proposed drive system with FEBC are explained in detail. The proposed FEBC has the significant benefit of being able to provide variable boosting voltages based on the dynamic behavior of the SR motor. The phase voltages are increased during the fast magnetization and demagnetization modes due to the inclusion of FEBC, and hence, quick magnetization and demagnetization have been achieved. The proposed FEBC drive system has been simulated through the Matlab Simulink toolbox. The experimental results are also carried out in order to validate the simulation results.
Single‐cell and spatial transcriptomics reveal POSTN+ cancer‐associated fibroblasts correlated with immune suppression and tumour progression in non‐small cell lung cancer
Authors: Chen Chao , Guo Qiang , Liu Yang , Hou Qinghua , Liao Mengying , Guo Yanying , Zang Yupeng , Wang Fei , Liu Huanyu , Luan Xinyu , Liang Yanling , Guan Zhuojue , Li Yanling , Liu Haozhen , Dong Xuan , Zhang Xiuqing , Liu Jixian , Xu Qumiao
Published: December 2023

Background

Cancer‐associated fibroblasts (CAFs) are potential targets for cancer therapy. Due to the heterogeneity of CAFs, the influence of CAF subpopulations on the progression of lung cancer is still unclear, which impedes the translational advances in targeting CAFs.

Methods

We performed single‐cell RNA sequencing (scRNA‐seq) on tumour, paired tumour‐adjacent, and normal samples from 16 non‐small cell lung cancer (NSCLC) patients. CAF subpopulations were analyzed after integration with published NSCLC scRNA‐seq data. SpaTial enhanced resolution omics‐sequencing (Stereo‐seq) was applied in tumour and tumour‐adjacent samples from seven NSCLC patients to map the architecture of major cell populations in tumour microenvironment (TME). Immunohistochemistry (IHC) and multiplexed IHC (mIHC) were used to validate marker gene expression and the association of CAFs with immune infiltration in TME.

Results

A subcluster of myofibroblastic CAFs, POSTN+ CAFs, were significantly enriched in advanced tumours and presented gene expression signatures related to extracellular matrix remodeling, tumour invasion pathways and immune suppression. Stereo‐seq and mIHC demonstrated that POSTN+ CAFs were in close localization with SPP1+ macrophages and were associated with the exhausted phenotype and lower infiltration of T cells. POSTN expression or the abundance of POSTN+ CAFs were associated with poor prognosis of NSCLC.

Conclusions

Our study identified a myofibroblastic CAF subpopulation, POSTN+ CAFs, which might associate with SPP1+ macrophages to promote the formation of desmoplastic architecture and participate in immune suppression. Furthermore, we showed that POSTN+ CAFs associated with cancer progression and poor clinical outcomes and may provide new insights on the treatment of NSCLC.
Flow field analysis and particle erosion of tunnel‐slope systems under coupling between runoff and fast (slow) seepage
Authors: Zhang Shuai , Song Danqing , Zhang Ruiliang , Zhang Kai , Zhao Qi , Sharma Suraksha
Published: December 2023

The presence of particles on the surface of a tunnel slope renders it susceptible to erosion by water flow, which is a major cause of soil and water loss. In this study, a nonlinear mathematical model and a mechanical equilibrium model are developed to investigate the distribution of flow fields and particle motion characteristics of tunnel slopes, respectively. The mathematical model of flow fields comprises three parts: a runoff region, a highly permeable soil layer, and a weakly permeable soil layer. The Navier‒Stokes equation controls fluid motion in the runoff region, while the Brinkman‐extended Darcy equation governs fast and slow seepage in the highly and weakly permeable soil layers, respectively. Analytical solutions are derived for the velocity profile and shear stress expression of the model flow field under the boundary condition of continuous transition of velocity and stress at the fluid‒solid interface. The shear stress distribution shows that the shear stress at the tunnel‐slope surface is the largest, followed by the shear stress of the soil interface, indicating that particles in these two locations are most vulnerable to erosion. A mechanical equilibrium model of sliding and rolling of single particles is established at the fluid‒solid interface, and the safety factor of particle motion (sliding and rolling) is derived. Sensitivity analysis shows that by increasing the runoff depth, slope angle, and soil permeability, the erosion of soil particles will be aggravated on the tunnel‐slope surface, but by increasing the particle diameter, particle‐specific gravity, and particle stacking angle, the erosion resistance ability of the tunnel‐slope surface particles will be enhanced. This study can serve as a reference for the analysis of surface soil and water loss in tunnel‐slope systems.
Female little brown bats require both building and natural roosts in a mountainous environment with short summers
Authors: Micalizzi E. W. , Forshner S. A. , Low E. B. , Johnston B. , Skarsgard S. A. , Barclay R. M. R.
Published: December 2023

The little brown bat (Myotis lucifugus) is an endangered species that occurs throughout most of North America. The recovery strategy for little brown bats in Canada identifies a need to understand habitat use and protect important bat habitat across the species' Canadian range; however, bat roosting habitat requirements have not been well studied in mountainous environments within the northern part of the species' range. Our objective was to understand the use of building and natural roosts by female little brown bats in the Canadian Rocky Mountains. Over two summers, we captured little brown bats in Banff, Yoho, and Kootenay National Parks, in Alberta and British Columbia, Canada, and tracked 49 females to their day roosts. Buildings were the only roost type used by radio‐tagged bats of all reproductive stages, the dominant roost type used throughout the reproductive period, and the only structures in which we located maternity colonies. Buildings also appeared to shape the distribution of foraging female and reproductive female bats such that few were captured at long distances from towns and building clusters. Compared with bats in more southern and in non‐mountainous areas, bats in our study area had delayed juvenile weaning and volancy, began hibernation early, and had low reproductive rates. We suggest that buildings are a key habitat for female little brown bats to persist at their current levels in our study area, by providing thermal conditions that promote overwinter survival; additional reproductive delays caused by torpor use in cool natural roosts would likely reduce juvenile and adult female overwinter survival below the levels required to sustain populations. Nevertheless, building colonies were unusually small, and bats had relatively low fidelity to particular building roosts, suggesting that building roosts may not consistently meet bats' needs. Some nonreproductive and pregnant females also frequently used natural roosts, particularly after colder nights; these roosts may be important in facilitating torpor and energy conservation for these bats. Because bats are long‐lived with low reproductive output and low juvenile survival, addressing the needs of both reproductive and nonreproductive individuals is important for population persistence.
N‐terminal pro‐B‐type natriuretic peptide concentrations, testing and associations with worsening heart failure events
Authors: Ferrannini Giulia , Benson Lina , Lautsch Dominik , Dahlström Ulf , Lund Lars H. , Savarese Gianluigi , Carrero Juan Jesus
Published: December 2023

Aims

In patients with heart failure (HF), we aimed to assess (i) the time trends in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) testing; (ii) patient characteristics associated with NT‐proBNP testing; (iii) distribution of NT‐proBNP levels, focusing on the subgroups with (WHFE) vs. without (NWHFE) a worsening HF event, defined as an HF hospitalization; and (iv) changes of NT‐proBNP levels over time.

Methods and results

NT‐proBNP testing and levels were investigated in HF patients enrolled in the Swedish Heart Failure Registry (SwedeHF) linked with the Stockholm CREAtinine Measurements project from January 2011 to December 2018. Index date was the first registration in SwedeHF. Patterns of change in NT‐proBNP levels before (in the previous 6 ± 3 months) and after (in the following 6 ± 3 months) the index date were categorized as follows: (i) <3000 ng/L at both measurements = stable low; (ii) <3000 ng/L at the first measurement and ≥3000 ng/L at the second measurement = increased; (iii) ≥3000 ng/L at the first measurement and <3000 ng/L at the second measurement = decreased; and (iv) ≥3000 ng/L at both measurements = stable high. Univariable and multivariable logistic regression models, expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs), were performed to assess the associations between (i) clinical characteristics and NT‐proBNP testing and (ii) changes in NT‐proBNP from 6 months prior to the index date and the index date and a WHFE. Consistency analyses were performed in HF with reduced ejection fraction (HFrEF) alone. A total of 4424 HF patients were included (median age 74 years, women 34%, HFrEF 53%), 33% with a WHFE. NT‐proBNP testing increased over time, up to 55% in 2018, and was almost two‐fold as frequent, and time to testing was less than half, in patients with WHFE vs. NWHFE. Independent predictors of testing were WHFE, higher heart rate, diuretic use, and preserved ejection fraction. Median NT‐proBNP was 3070 ng/L (Q1–Q3: 1220–7395), approximately three‐fold higher in WHFE vs. NWHFE. Compared with stable low NT‐proBNP levels, increased (OR 4.27, 95% CI 2.47–7.37) and stable high levels (OR 2.48, 95% CI 1.58–3.88) were independently associated with a higher risk of WHFE. Results were consistent in the HFrEF population.

Conclusions

NT‐proBNP testing increased over time but still was only performed in half of the patients. Testing was associated with a WHFE, with features of more severe HF and for differential diagnosis purposes. Increased and stable high levels were associated with a WHFE. Overall, our data highlight the potential benefits of carrying further implementation of NT‐proBNP testing in clinical practice.
Vinylene Carbonate as Latent Formylmethyl Surrogate: The Expediency of Ruthenium(II) Catalysis in Accessing Arylacetaldehydes, Arylacetates and Acetals
Authors: Thalakottukara Dolly David , Gandhi Thirumanavelan
Published: December 2023

Arylacetaldehydes and its corresponding esters are fundamental structural motifs widespread in natural products and pharmaceuticals. Herein, we developed a ruthenium(II)‐catalyzed direct formylmethylation and sequential dehydrogenative esterification of phthalazinones by adopting vinylene carbonate as a C2 synthon (formylmethyl equivalent). The reaction is compatible with a repertoire of substrates bearing both electron‐donating and electron‐withdrawing substituents. Strikingly, the products obtained are governed by the additive used. A number of control experiments are conducted to elucidate the reaction mechanism. Furthermore, an important highlight is confirmation of possible intermediates by mass spectrometry.
Convolutional Neural Network‐Long Short‐Term Memory‐Based State of Health Estimation for Li‐Ion Batteries under Multiple Working Conditions
Authors: Feng Shuzhen , Song Mingyu , Lin Yongjun , Yao Wanye , Xie Jiale
Published: December 2023

The state of health (SOH) for lithium‐ion batteries is an important indicator to ensure the safety and reliability of battery energy storage systems. Aiming at the difficulty of accurately estimating the SOH of lithium‐ion batteries under different working conditions, this article proposes a method based on a hybrid convolutional neural network‐long short‐term memory (CNN‐LSTM) model. First, the battery health indicators and capacity data under different operating conditions are extracted from the public dataset to form a new dataset. Second, the CNN has multiple one‐dimensional convolutional layers to improve the efficiency of feature extraction from new datasets, and the resulting features are used as inputs to the LSTM to predict SOH. Finally, the CNN‐LSTM model integrates a fully connected layer that outputs the estimation of SOH for different operating conditions. The results show that the mean absolute error of the SOH estimation results is within 2.33% and 3.01% for the same and different working conditions, respectively.
Learn how to interpret and use intracranial EEG findings
Authors: Frauscher B. , Mansilla D. , Abdallah C. , Astner‐Rohracher A. , Beniczky S. , Brazdil M. , Gnatkovsky V. , Jacobs J. , Kalamangalam G. , Perucca P. , Ryvlin P. , Schuele S. , Tao J. , Wang Y. , Zijlmans M. , McGonigal A.
Published: December 2023

Epilepsy surgery is the therapy of choice for many patients with drug‐resistant focal epilepsy. Recognizing and describing ictal and interictal patterns with intracranial electroencephalography (EEG) recordings is important in order to most efficiently leverage advantages of this technique to accurately delineate the seizure‐onset zone before undergoing surgery. In this seminar in epileptology, we address learning objective “1.4.11 Recognize and describe ictal and interictal patterns with intracranial recordings” of the International League against Epilepsy curriculum for epileptologists. We will review principal considerations of the implantation planning, summarize the literature for the most relevant ictal and interictal EEG patterns within and beyond the Berger frequency spectrum, review invasive stimulation for seizure and functional mapping, discuss caveats in the interpretation of intracranial EEG findings, provide an overview on special considerations in children and in subdural grids/strips, and review available quantitative/signal analysis approaches. To be as practically oriented as possible, we will provide a mini atlas of the most frequent EEG patterns, highlight pearls for its not infrequently challenging interpretation, and conclude with two illustrative case examples. This article shall serve as a useful learning resource for trainees in clinical neurophysiology/epileptology by providing a basic understanding on the concepts of invasive intracranial EEG.
A decreased level of high‐density lipoprotein is a possible risk factor for type 2 diabetes mellitus: A review
Authors: Bodaghi Ali Bayat , Ebadi Erfan , Gholami Mohammad Javad , Azizi Reza , Shariati Aref
Published: December 2023

Introduction

Type 2 diabetes mellitus (T2DM) is characterized primarily by dyslipidemia and hyperglycemia due to insulin resistance. High‐density lipoprotein (HDL) play a significant role in preventing the incidence of dyslipidemia and its complications. HDL has different protective functions, such as reducing oxidation, vascular inflammation, and thrombosis; additionally, its anti‐diabetic role is one of the most significant recent discoveries about HDL and some of its constituent lipoproteins.

Methods

This research reviews ongoing studies and preliminary investigations into the assessment of relation between decreased level of HDL and T2DM.

Results

The levels of HDL and its functions contribute to glucose hemostasis and the development of T2DM through four possible mechanisms, including insulin secretion by beta cells, peripheral insulin sensitivity, non‐insulin‐dependent glucose uptake, and adipose tissue metabolic activity. Additionally, the anti‐oxidant properties of HDL protect beta cells from apoptosis caused by oxidative stress and inflammation induced by low‐density lipoprotein, which facilitate insulin secretion.

Conclusion

Therefore, HDL and its compositions, especially Apo A‐I, play an important role in regulating glucose metabolism, and decreased levels of HDL can be considered a risk factor for DM. Different factors, such as hypoalphalipoproteinemia that manifests as a consequence of genetic factors, such as Apo A‐I deficiency, as well as secondary causes arising from lifestyle choices and underlying medical conditions that decrease the level of HDL, could be associated with DM. Moreover, intricate connections between HDL and diabetic complications extend beyond glucose metabolism to encompass complications like cardiovascular disease and kidney disease. Therefore, the exact interactions between HDL level and DM should be evaluated in future studies.
Reducing heat gain from sheet metal‐clad walls by utilizing industrially wasted materials (experimental study)
Authors: Khaleel Mahmood H. , Hasan Atif Ali , Al‐Bayati Omer Adil Zainal
Published: December 2023

Buildings' walls are covered to reduce environmental impact and esthetics, and cladding materials vary based on public preference and financial capacity. Metal sheets with glossy surfaces are commonly used, but researchers propose using aluminum sheets and filling gaps with commercial waste materials, like, fabric roll sticks or circular plastic hollow parts. A test room with internal dimensions of 1 × 1 × 2 m used in Baghdad (latitude 33.2° N) was used to study thermal behavior, with a window‐type air conditioner providing standard thermal conditions. The air gap attached to the top of the test wall was either left open or closed during the day. Results showed that double‐layer bamboo packing preserved 52.1% with a closed‐air gap and 49.5% with an open‐air gap, but no discernible difference was observed between the two situations.
Schizosaccharomyces pombe as a fundamental model for research on mitochondrial gene expression: Progress, achievements and outlooks
Authors: Dinh Nhu , Bonnefoy Nathalie
Published: December 2023

Schizosaccharomyces pombe (fission yeast) is an attractive model for mitochondrial research. The organism resembles human cells in terms of mitochondrial inheritance, mitochondrial transport, sugar metabolism, mitogenome structure and dependence of viability on the mitogenome (the petite‐negative phenotype). Transcriptions of these genomes produce only a few polycistronic transcripts, which then undergo processing as per the tRNA punctuation model. In general, the machinery for mitochondrial gene expression is structurally and functionally conserved between fission yeast and humans. Furthermore, molecular research on S. pombe is supported by a considerable number of experimental techniques and database resources. Owing to these advantages, fission yeast has significantly contributed to biomedical and fundamental research. Here, we review the current state of knowledge regarding S. pombe mitochondrial gene expression, and emphasise the pertinence of fission yeast as both a model and tool, especially for studies on mitochondrial translation.
From macro to micro: A close‐up look atHydrangea luteovenosaandHydrangea serrata
Authors: Zaman Wajid , Park Seongjun , Lee Eun Mi , Choi Sumi , Hwang SaeYeon , Park SeonJoo
Published: December 2023

Understanding the anatomical traits of the foliar epidermis is essential for making precise species identification and categorization. In this study, scanning electron microscopy (SEM) was used to examine the taxonomically significant foliar epidermal traitsof Hydrangea luteovenosaandH. serrata. The qualitative and quantitative traits observed included the epidermal cell form, cuticle presence, trichome morphology, stomatal type, and guard cell features.H. serratahad a thin and smooth cuticle, and epidermal cells organized compactly into cubic or hexagonal shapes. The stomata were of the anomocytic type and dispersed, while the trichomes were straightforward, unbranched, and distributed sparsely. The guard cells had distinct cell walls and a kidney‐shaped morphology. These crucial traits for taxonomy were in line with an epidermis composed of three to five layers. Similar polygonal epidermal cells with a compact arrangement were observed inH. luteovenosa, together with a thin and smooth cuticle. The stomata were anomocytic and dispersed, while the trichomes were straightforward, unbranched, and sparsely distributed. The guard cells have distinct cell walls and a kidney‐shaped morphology. The traits were indicative of an epidermal structure with three to five layers. These traits helped correctly identify and categorize these two species ofHydrangea. In addition to assisting in the taxonomic classification of these species and advancing knowledge of their ecological and evolutionary links, the SEM study provided insightful information into the structural variety of these species.

Research Highlights

Microscopic characteristics ofH. luteovenosaandH. serrata

Understanding the anatomical traits of the foliar epidermis is essential for precise species identification and categorization
The effects of HPV oncoproteins on host communication networks: Therapeutic connotations
Authors: Skelin Josipa , Luk Ho Yin , Butorac Dražan , Boon Siaw Shi , Tomaić Vjekoslav
Published: December 2023

Human papillomavirus (HPV) infections are a leading cause of viral‐induced malignancies worldwide, with a prominent association with cervical and head and neck cancers. The pivotal role of HPV oncoproteins, E5, E6, and E7, in manipulating cellular events, which contribute to viral pathogenesis in various ways, has been extensively documented. This article reviews the influence of HPV oncoproteins on cellular signaling pathways within the host cell, shedding light on the underlying molecular mechanisms. A comprehensive understanding of these molecular alterations is essential for the development of targeted therapies and strategies to combat HPV‐induced premalignancies and prevent their progress to cancer. Furthermore, this review underscores the intricate interplay between HPV oncoproteins and some of the most important cellular signaling pathways: Notch, Wnt/β‐catenin, MAPK, JAK/STAT, and PI3K AKT/mTOR. The treatment efficacies of the currently available inhibitors on these pathways in an HPV‐positive context are also discussed. This review also highlights the importance of continued research to advance our knowledge and enhance therapeutic interventions for HPV‐associated diseases.
Generalized memory polynomial input neural networks for nonlinear modeling in digital predistortion applications
Authors: Mu Qin , Li Nanxi , Liu Ying , Du Linsong , Wei Xiaozheng , Long Zixuan
Published: December 2023

The power amplifiers (PAs) will embody the nonlinear distortion if they work at saturation so as to increase efficiency. The neural network (NN)‐based digital predistortion (DPD) is widely applied for the linearization of the PA in wireless communication. However, the current NN‐based DPD schemes only focus on designing the NN hidden layer and ignore improving the NN input layer, which loses the degree of freedom to fit the DPD. Therefore, this paper first proposes the generalized memory polynomial (GMP) input NN structure. The training data of GMP‐NN outputs are obtained by iterative learning control. The experimental results show that the GMP‐NN presents a great advantage in performance compared with the widely used GMP model and recurrent NN (RNN) model. From the testing data, it is observed that the minimum mean square error (MMSE) of the GMP‐NN is 4 dB lower than the conventional GMP model and is nearly 8 dB lower than the RNN model. The proposed GMP‐NN model is also verified in the DPD application, which shows 2.61 dB improvement in comparison with the GMP DPD model.
Unearthing diverse culturable fungal communities associated with Ophiocordyceps indica sp. nov. from Indian Western Himalaya
Authors: Sharma Aakriti , Ranout Aditya Singh , Kaur Rupinder , Kumari Pooja , Nadda Gireesh
Published: December 2023

Fungal communities colonizing Ophiocordyceps spp. plays a crucial ecological role in their natural habitat, contributing to infect the host larvae, and influencing their occurrence. Although associated fungi with the newly described Ophiocordyceps indica, from the Indian Western Himalaya remains unclear. Therefore, we untangled the culturable fungal communities associated with O. indica and soil adhered to it, collected from low‐height areas of Himachal Pradesh, India. The study resulted in the identification of 111 fungal isolates representing 17 families, with maximum fungal isolates (36.03%) within Cordycipitaceae. Interestingly, a total of 24 genera were found associated with O. indica and adhered soil, of which 12 were common, 8 were exclusive to O. indica and 4 were only limited to soil. Additionally, the influence of soil physicochemical parameters on fungal diversity indices revealed a positive correlation with humidity and available nitrogen and a negative correlation with pH and available phosphorus. These findings provide insights into the culturable fungal diversity of O. indica and the soil adhering to it, thus can contribute to the understanding of host‐microbial interactions. Furthermore, these associations can be explored as a source of bioactive metabolites to combat the unending industrial demands.
Late Wolstonian and Ipswichian (MIS 6/5e) sediment fill in a limestone sinkhole, Askham Fell, northern England
Authors: Carling Paul A. , Evans David J. A. , Abbas Mahmoud , Ou Xianjiao , Lai Zhongping
Published: December 2023

In 2019 a sinkhole (doline) occurred in Late Devensian till above fissured limestone in northern England. Most sediment plugging the fissure was evacuated down into a karstic drainage system. The residual sedimentary fill comprises three main lithofacies, dated using optically stimulated luminescence to between 170.7 ± 40.0 and 56.1 ± 13.5 ka. The earliest date demonstrates fissures were present in the limestone pavement at the time of Marine Isotope Stage (MIS) 6, or shortly thereafter. The fissure filled with fine sand and silt due to surface runoff and aeolian processes probably at the MIS 6 to MIS 5e transition after Wolstonian glacial ice had retreated. The deposits then collapsed into the karst system. Further fine sand and silt deposition occurred during MIS 3; this deposit filled the central cavity surrounded by residual MIS 6/5e deposits. The sequence was capped by till as Late Devensian (MIS 2) ice transgressed the area. Solution fissures in the karst surfaces of northern England may pre‐date the Late Devensian glaciation. Moreover, fissures are repositories of pre‐Devensian sediment deposits which survived the Late Devensian glaciation and the Ipswichian interglacial. Such sites should provide information on the nature and timing of pre‐Devensian glacial–interglacial events and shed light on basal ice conditions and glaciokarst drainage behaviour.
Nonintensive topical gentamicin treatment of patients with severe epidermolysis bullosa caused by nonsense mutations
Authors: Sandanger Ø. , Torp M. K. , Glesaaen A. , Nilsen H. R. , Sitek J. C.
Published: December 2023

Background

Severe epidermolysis bullosa (EB) is caused by premature termination codons (PTCs) in a significant minority of the patients. Topical gentamicin has been shown to increase wound healing and can restore protein translation in patients with EB through PTC suppression. However, only intensive treatment of limited wound areas have been reported previously.

Objectives

The objectives of this study is to investigate whether nonintensive topical gentamicin therapy is an effective wound‐healing treatment in patients with severe EB caused by PTCs.

Methods

A randomized, open‐controlled, single‐centre, single‐arm clinical trial designed to determine effectiveness at an individual level was performed. Each patient served as their own control and received topical 0.1% gentamicin ointment once daily for 6 weeks on all wounds on one body half. Wound areas were measured at Weeks 0 and 6. Change in wound areas at Week 6 compared with baseline was calculated and the changes in treated areas were compared with control areas. Immunohistochemistry was performed at Weeks 0 and 6.

Results

Four patients were included. One patient withdrew before completion. No significant effect on wound healing was seen. Immunohistochemistry analysis supported successful PTC suppression in two patients.

Conclusions

Our data suggest that nonintensive topical treatment with 0.1% gentamicin ointment for 6 weeks does not improve wound healing.
Research Progress of Large Viewing‐Area 3D Holographic Near‐Eye Display
Authors: Liu Taijiang , Ning Honglong , Cao Hongkun , Luo Dongxiang , Xu Zhuohui , Luo Cheng , Su Guoping , Liu Yuxiang , Yao Rihui , Peng Junbiao
Published: December 2023

With the development of the information industry, the wearable three‐dimensional (3D) near‐eye display that can provide complete visual information has attracted increasing attention. Compared with other existing 3D display technologies, the holographic display is a promising true 3D display technology that can fully record and reproduce the original 3D scenes. The ability to present a continuous parallax and depth perception gives holography technology an unprecedented promise in the next‐generation 3D near‐eye display. However, currently available holographic near‐eye display systems can only provide a limited viewing area (including the field of view and eyebox), greatly restricting its practical application. Focusing on the development requirements of large viewing‐area 3D holographic near‐eye display, the reasons are introduced first why the viewing area of current holographic displays is limited and then the existing solutions from different aspects, including multiplexing‐based methods, steering viewing window methods, aperiodic wavefront modulation methods, and some emerging holographic display technologies are summarized. These various solutions are analyzed respectively, and their representative works are investigated. In addition, the different applications of holography in the near‐eye display system are also discussed. Finally, the advantages and disadvantages of these techniques are compared and perspectives are given.
Mechanisms and therapeutic strategies of extracellular vesicles in cardiovascular diseases
Authors: Li Qirong , Feng Qiang , Zhou Hengzong , Lin Chao , Sun Xiaoming , Ma Chaoyang , Sun Liqun , Guo Gongliang , Wang Dongxu
Published: December 2023

Cardiovascular disease (CVD) significantly impacts global society since it is the leading cause of death and disability worldwide, and extracellular vesicle (EV)‐based therapies have been extensively investigated. EV delivery is involved in mediating the progression of CVDs and has great potential to be biomarker and therapeutic molecular carrier. Besides, EVs from stem cells and cardiac cells can effectively protect the heart from various pathologic conditions, and then serve as an alternative treatment for CVDs. Moreover, the research of using EVs as delivery carriers of therapeutic molecules, membrane engineering modification of EVs, or combining EVs with biomaterials further improves the application potential of EVs in clinical treatment. However, currently there are only a few articles summarizing the application of EVs in CVDs. This review provides an overview of the role of EVs in the pathogenesis and diagnosis of CVDs. It also focuses on how EVs promote the repair of myocardial injury and therapeutic methods of CVDs. In conclusion, it is of great significance to review the research on the application of EVs in the treatment of CVDs, which lays a foundation for further exploration of the role of EVs, and clarifies the prospect of EVs in the treatment of myocardial injury.