bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comprehensive Comparative Study on Pyrolysis Kinetics and Process of Organic‐Rich Mudstone and Kerogen via Thermogravimetry and Peak Deconvolution
Authors: Li Yaoyu , Zhou Shixin , Li Jing , Sun Zexiang , Pang Wenjun
Published: January 2024

Pyrolytic oil production from kerogens is of scientific and industrial importance for the efficient utilization of oil resources. Minerals exert a significant impact on this process. In this study, the pyrolysis kinetics and process of organic‐rich mudstones and kerogens in the Junggar basin are investigated by characterization and thermogravimetric experiments. The major minerals in the kerogen, except pyrite, are eliminated by HF/HCl treatment. To conduct a detailed comparison of the pyrolysis kinetics of rocks and kerogens, the pyrolysis process of kerogens is deconvoluted into two stages, including the pyrolysis oil production process and the conversion of sulfur compounds. The results show that the pyrolysis kinetics and reaction models of sulfur compounds differ significantly from those of the hydrocarbon production process. Furthermore, the effects of minerals on the pyrolysis products are analyzed using thermogravimetric‐Fourier‐transform infrared spectrometer. The main pyrolytic volatilization products include C2+ aliphatics, CH4, CO2, SO2, CO, and SO bonded substances. Minerals can increase the activation energy of organic matter pyrolysis, but the effect on the reaction model can be negligible. Moreover, minerals can promote the condensation dehydrogenation of aromatics and inhibit the cleavage of aliphatics. Notably, organic matter can act as active sites in the formation of sulfur compounds.
Quantitative evaluation of China's energy supply policies in the ‘13th Five‐Year Plan’ period (2016–2020): A PMC index modelling approach incorporating text mining
Authors: Cheng Quan , Chen Zhongzhen , Lin Minwang , Wang Haiyan
Published: January 2024

Energy supply policy quality is an important factor that would impact national energy security. While existing research conducted policy evaluation from the lens of performance assessment, less study has been devoted to evaluating energy supply policy from the perspective of policy making. This study takes the energy supply policy documents issued by China's central government during the ‘13th Five‐Year Plan’ period (2016–2020) as the research sample, and pioneers the use of the extended policy modelling consistency (PMC) index model combined with the text mining methodology to construct a policy evaluation index system with the characteristics of the energy supply policy which conducts a more in‐depth quantitative evaluation of the energy supply policy documents. The results show that the average PMC index value of China's energy supply policies is 7.26, and the overall quality is high. The concerns of existing policies are mainly focused on reform and development planning, safety production management and project engineering construction, but there is still room for improvement in policy predictability, coordination of policy areas, clarity of policy basis and goals and comprehensiveness of policy tool combinations. Based on this, China should improve the comprehensiveness of its energy supply policy tool combinations in terms of policy design norm; strengthen policy predictability and coordination of policy areas in terms of policy implementation guarantee; and clarify the basis and goals of policies in terms of policy orientation enhancement, to provide a reference basis for the formulation and improvement of future energy supply policies and to realise the sustainable development of energy supply.
Relationship between topological efficiency of white matter structural connectome and plasma biomarkers across the Alzheimer's disease continuum
Authors: Zhang Mingkai , Chen Haojie , Huang Weijie , Guo Tengfei , Ma Guolin , Han Ying , Shu Ni
Published: January 2024

Both plasma biomarkers and brain network topology have shown great potential in the early diagnosis of Alzheimer's disease (AD). However, the specific associations between plasma AD biomarkers, structural network topology, and cognition across the AD continuum have yet to be fully elucidated. This retrospective study evaluated participants from the Sino Longitudinal Study of Cognitive Decline cohort between September 2009 and October 2022 with available blood samples or 3.0‐T MRI brain scans. Plasma biomarker levels were measured using the Single Molecule Array platform, including β‐amyloid (Aβ), phosphorylated tau181 (p‐tau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). The topological structure of brain white matter was assessed using network efficiency. Trend analyses were carried out to evaluate the alterations of the plasma markers and network efficiency with AD progression. Correlation and mediation analyses were conducted to further explore the relationships among plasma markers, network efficiency, and cognitive performance across the AD continuum. Among the plasma markers, GFAP emerged as the most sensitive marker (linear trend: t = 11.164, p = 3.59 × 10−24; quadratic trend: t = 7.708, p = 2.25 × 10−13; adjusted R2 = 0.475), followed by NfL (linear trend: t = 6.542, p = 2.9 × 10−10; quadratic trend: t = 3.896, p = 1.22 × 10−4; adjusted R2 = 0.330), p‐tau181 (linear trend: t = 8.452, p = 1.61 × 10−15; quadratic trend: t = 6.316, p = 1.05 × 10−9; adjusted R2 = 0.346) and Aβ42/Aβ40 (linear trend: t = −3.257, p = 1.27 × 10−3; quadratic trend: t = −1.662, p = 9.76 × 10−2; adjusted R2 = 0.101). Local efficiency decreased in brain regions across the frontal and temporal cortex and striatum. The principal component of local efficiency within these regions was correlated with GFAP (Pearson's R = −0.61, p = 6.3 × 10−7), NfL (R = −0.57, p = 6.4 × 10−6), and p‐tau181 (R = −0.48, p = 2.0 × 10−4). Moreover, network efficiency mediated the relationship between general cognition and GFAP (ab = −0.224, 95% confidence interval [CI] = [−0.417 to −0.029], p = .0196 for MMSE; ab = −0.198, 95% CI = [−0.42 to −0.003], p = .0438 for MOCA) or NfL (ab = −0.224, 95% CI = [−0.417 to −0.029], p = .0196 for MMSE; ab = −0.198, 95% CI = [−0.42 to −0.003], p = .0438 for MOCA). Our findings suggest that network efficiency mediates the association between plasma biomarkers, specifically GFAP and NfL, and cognitive performance in the context of AD progression, thus highlighting the potential utility of network‐plasma approaches for early detection, monitoring, and intervention strategies in the management of AD.
Maternal postnatal depressive symptoms and early achievement of developmental milestones in infants and young children: A meta‐analysis
Authors: Racine Nicole , Wu Pauline , Pagaling Rachel , O'Reilly Hannah , Brunet Ganaëlle , Birken Catherine S. , Lorenzetti Diane L. , Madigan Sheri
Published: January 2024

Screening for social determinants of health, including maternal depression, is a recommended pediatric practice. However, the magnitude of association between maternal and child screening tools remains to be determined. The current study evaluated the association between maternal postnatal depressive symptoms and child developmental milestones, as well as moderators of these associations. A comprehensive search strategy was carried out in four databases (MEDLINE, EMBASE, APA PsycINFO, and Cochrane Central Register of Controlled Trials) from database inception to September 2022. Studies that examine postnatal depressive symptoms and associations with infant and early child (<6 years) achievement of developmental milestones were included. Data were extracted by two independent coders and a random‐effects meta‐analysis was used to estimate pooled effect sizes and test for moderators. A total of 38 non‐overlapping studies (95,897 participants), all focused on maternal postnatal depression, met inclusion criteria. The pooled effect size for the association between postnatal depressive symptoms and early achievement of infant and child developmental milestones (N = 38; r = −.12; 95% CI = −.18, −.06) was small in magnitude. Child age at maternal depression measurement was a moderator, whereby effect sizes became greater for older children. Despite small effects, maternal postnatal depressive symptoms should be included in screening during routine well‐child visits to enhance child development outcomes.
Dynamic fluorescence molecular tomography metabolic parameters solution based on problem decomposition and prior refactor
Authors: Wei Xiao , Guo Hongbo , Zhao Yizhe , Wang Beilei , Yu Jingjing , He Xiaowei
Published: January 2024

Dynamic fluorescence molecular tomography (DFMT), as a noninvasive optical imaging method, can quantify metabolic parameters of living animal organs and assist in the diagnosis of metabolic diseases. However, existing DFMT methods do not have a high capacity to reconstruct abnormal metabolic regions, and require additional prior information and complicated solution methods. This paper introduces a problem decomposition and prior refactor (PDPR) method. The PDPR decomposes the metabolic parameters into two kinds of problems depending on their temporal coupling, which are solved using regularization and parameter fitting. Moreover, PDPR introduces the idea of divide‐and‐conquer to refactor prior information to ensure discrimination between metabolic abnormal regions and normal tissues. Experimental results show that PDPR is capable of separating abnormal metabolic regions of the liver and has the potential to quantify metabolic parameters and diagnose liver metabolic diseases in small animals.
Exploring Canadian genetic counselors' perspectives and experiences with discussing medical assistance in dying (MAiD)
Authors: Candlish Rebecca C. , Creighton Susan , Pullman Daryl , Elliott Alison M.
Published: January 2024

Medical assistance in dying (MAiD) is the Canadian equivalent of Physician aid‐in‐dying (PAD) in the United States. Through changes to the eligibility criteria for MAiD in 2021, Canada now has one of the most permissive assisted dying regimens in the world. This study describes Canadian genetic counselors' experiences, knowledge, and preparedness to discuss MAiD with their patients. Survey responses were collected from Canadian genetic counselors (n = 44) and were followed by semi‐structured interviews with 14 survey participants. Survey data were analyzed using descriptive statistics, and interview transcripts were analyzed using phronetic iterative analysis and an interpretive description approach. Survey data revealed that genetic counselors have discussed MAiD with patients referred for cancer, neurologic, metabolic, connective tissue, and cardiac indications (n = 18, 40.9%). While most thought that it was important for genetic counselors to be knowledgeable of (n = 41, 93.2%) and prepared to discuss MAiD (n = 43, 97.7%), many were not familiar with the eligibility criteria (n = 27, 61.4%) and the process for accessing MAiD in Canada (n = 29, 65.9%). Interview participants described discussions about MAiD that were initiated by themselves or their patients. Most participants felt prepared to explore a patient's thoughts about MAiD when the patient initiated the discussion but did not feel well‐prepared to share detailed information about MAiD. Participants were interested in education and professional guidance to assist them in preparing to discuss MAiD. Learning objectives were developed based on participants' suggestions to assist genetic counselors in their clinical work and self‐directed research and to aid in the development of professional guidelines and educational materials for practicing genetic counselors and genetic counseling trainees. As genetic counselors continue engaging in discussions about MAiD, it is critical that these sensitive conversations are approached with increased knowledge and awareness of MAiD legislation, the ethical issues surrounding MAiD in Canada, and relevant patient resources.
Evaluation of the effects of three different processing methods of aconite on rat metabolites based on high‐coverage pseudotargeted metabolomics
Authors: Wu Huifei , Zhang Wenxia , Wang ZhiEn , Lin Hui , Guo Jiayin , Quan Shijian
Published: January 2024

Aconite is the processed product of the seed root of Aconitum carmichaelii Debx. Aconite is a commonly used traditional Chinese medicine, which is generally used after processing. Black aconite, light aconite, and salted aconite are three different processed aconite products. They have the effects of restoring yang and saving energy enemy, dispersing cold, and relieving pain. However, clinical aconite poisoning cases have frequently been reported. In our study, we investigated the effects of three different processed aconite products on the changes of metabolites in vivo. A total of 42 rats were randomly divided into seven groups with six rats in each group. After three consecutive days of intragastric administration of 2.7 g/kg of the aconite‐processed product, rat serums were obtained. The rat metabolites were detected using liquid chromatography‐tandem mass spectrometry. The altered metabolites related to aconite‐processed products were discovered by statistical analysis using metaboanalyst software. Our study is the first time to comprehensively evaluate the effects of three different processed aconite products on rat metabolites based on pseudotargeted metabolomics.
Metabolomics‐based pharmaceutical evaluation of different parts of Swertia chirayita (Roxb.) Buch.‐Ham. ex C.B. Clarke from the western Himalayas
Authors: Tewari Devesh , Bawari Sweta , Mishra Saurabh T , Gupta Pawan , M Aryalaxmi , Cziáky Zoltán , Jeko József , Lazarova Irina , Zengin Gökhan
Published: January 2024

Swertia species are common ingredients in numerous herbal remedies. It is also used to treat a wide range of illnesses and possess diverse therapeutic activities. The aim of the study is to elucidate the comprehensive metabolomics profile of Swertia chirayita and the role of various extraction methods in the phytochemical compositions of the extracts of S. chirayita, and their antioxidant and enzyme inhibitory activities. Extraction of the stems, leaves, and flowering tops of S. chirayita was performed by maceration, infusion, and soxhlation using methanol and water as solvent. Extracts were subjected to phytochemical profiling by a liquid‐chromatographic system. Antioxidant and enzyme inhibitory activity was carried out. The metabolomics profiling showed that a diverse range of specialized metabolites were present in the stems and leaves & flowering tops of the plant. All the extracts showed substantial antioxidant and enzyme inhibitory activities further confirmed by molecular docking studies. This study appraised the use of S. chirayita aerial parts as a potential antioxidant and its therapeutic application in various chronic illnesses including Alzheimer's disease, diabetes, and other skin‐related disorders.
Ethylenediamine Salt Enhances the Solubility and Dissolution of Flurbiprofen
Authors: Gao Lei , Li Xiaojie , Yan Xiaolin , Zhang Xianrui
Published: January 2024

Drugs that are poorly soluble in water are difficult to absorb orally, resulting in low bioavailability. Flurbiprofen (FLU) is an arylpropionic acid nonsteroidal anti‐inflammatory drug belonging to BCS class II, with low water solubility. In this study, a novel flurbiprofen‐ethylenediamine salt (FLU‐EDA) was successfully prepared via solvent crystallization. Its crystal structure was determined via single‐crystal X‐ray diffraction (SXRD). Further, the physicochemical properties of FLU‐EDA salt were characterized by powder X‐ray diffraction (PXRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT‐IR). The solubility and intrinsic dissolution rate (IDR) of FLU‐EDA salt in water were investigated. The results showed that compared with FLU, the solubility and IDR of FLU‐EDA salt increased by 57‐fold and 32‐fold, respectively. This indicates that FLU‐EDA salt can significantly enhance the solubility and dissolution rate of flurbiprofen in water. This study provides basic data and theory for the development of new formulations of flurbiprofen.
Extracervical Approaches to Substernal Thyroid Goiter Resection: A Systematic Review and Meta‐Analysis
Authors: Khan Najm S. , Zhang Yingting , Bollig Kassie , Bollig Craig A.
Published: January 2024

Objective

To evaluate the prevalence of extracervical approaches (ECAs) for substernal goiter (SSG) excision.

Data Sources

Search strategies created in collaboration with a medical librarian were implemented using PubMed, Cochrane, Scopus, Web of Science, and Google Scholar from inception to July 2021.

Review Methods

Participants included adults ages >18 years undergoing SSG excision. The primary outcome was rate of ECA via sternotomy or thoracotomy. Studies were categorized into the 3 most common distinct definitions: goiter descending below the plane of the thoracic inlet (definition 1), ≥50% of thyroid mass extending below the sternal notch (definition 2), and goiter extending ≥3 cm below the suprasternal notch when the neck is hyperextended (definition 3). Two reviewers independently extracted data for analysis and performed a quality assessment using the Methodological Index for Non‐Randomized Studies criteria.

Results

Of the 551 studies identified, 69 studies were included for analysis. Definition 1 included 3441 patients from 31 studies; definition 2 included 2957 patients from 26 studies; and definition 3 included 2921 patients from 12 studies. A random‐effect model estimating the pooled prevalence of ECA using definition 1 resulted in prevalence of 6.12% (95% confidence interval: 3.48‐9.34, I2 = 90.72%).

Conclusion

Extension below the thoracic inlet is the most widely used definition of SSG. Approximately 6% of patients with a SSG undergo an ECA. Patients with SSG undergoing surgery should be counseled on the prevalence, risks, and morbidity of an ECA in the rare occurrence it is needed.
Does anti‐HPA‐1a affect birthweight in fetal and neonatal alloimmune thrombocytopenia?
Authors: McKelvy Margaret , Tyagi Srishti , Haar Emilie Vander , Lakkaraja Madhavi , Tomy Tim , Corke Stacy , Palmer Thea , Rottenstreich Amihai , Kapur Rick , Zhi Huiying , Newman Debra , Scatz‐Siemers Nina , Bussel James
Published: January 2024

Background

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) ensues from parental incompatibility for platelet alloantigens with maternal sensitization. HPA‐1a/1b incompatibility is the most common cause of FNAIT in Caucasians. Placental villitis and lower birthweight in FNAIT suggest anti‐HPA‐1a may have effects beyond inducing thrombocytopenia.

Objectives

Does FNAIT secondary to anti‐HPA‐1a result in smaller newborns and, the corollary, does antenatal management of FNAIT increase birthweight?

Study design

Birthweights of 270 FNAIT‐affected newborns from a randomized clinical trial and a NAITbabies.org survey (135 paired siblings) were compared with those of published controls and treated to untreated FNAIT‐affected siblings. Birthweights were converted to percentiles to account for gestational age, sex, and role of birth order in birth weight. Body weights of FNAIT‐affected and ‐unaffected pups in a mouse FNAIT model were analyzed.

Results

Untreated siblings in both the clinical trial and NAITbabies.org cohorts were not small, compared with normal controls. However, treated siblings in both cohorts had significantly higher birthweight percentiles compared with their previous untreated affected sibling. After accounting for gestational age, sex, and birth order, increased birthweight percentile in treated compared with the untreated siblings remained significant in both cohorts. FNAIT‐affected neonatal mice had lower bodyweights than FNAIT‐unaffected pups.

Conclusions

Untreated FNAIT‐affected newborns were not small; however, treatment of FNAIT‐affected pregnancies increased newborn birthweights despite corrections to account for other factors that might have influenced the results. High dose IVIG is believed to “block” FcRn and lower maternal anti‐HPA‐1a levels, and thus increase birthweights by reducing levels of maternal anti‐HPA‐1a and reducing placental villitis.
Exploring the effects of automation malfunction on team communication and coordination in ships' engine rooms
Authors: Tusher Hasan Mahbub , Nazir Salman , Mallam Steven , Yang Zaili , Asgher Umer , Rusli Risza
Published: January 2024

Automation malfunctions within complex socio‐technical systems reserve the potential to significantly affect human performance. In the context of maritime operations, varying consequences of automation malfunction on human performance can be observed. This study introduced a two‐step research framework to examine the repercussions of such malfunctions, particularly those related to communication and coordination among human teams in ship engine rooms. Initially, a qualitative semi‐structured interview was conducted with seven professional marine engineers to explore the potential impact of hypothetical automation malfunction on team communication. Subsequently, a quantitative survey involving 32 professional marine engineers employed coordination demand analysis (CDA) to scrutinize changes in team coordination resulting from malfunction. The findings indicate that an automation malfunction within an engine room can precipitate an abrupt overload of the socio‐technical system. This can significantly increase communication frequency among engineers, particularly in relation to the physical and organizational aspects of the environment. Furthermore, the study highlights the influence of disparate levels of expertise among team members on coordination demands. A positive correlation was discovered between differences in expertise and increased coordination demands within a team. These insights underscore the necessity for future research on human–automation interaction, specifically focusing on individual differences and nontechnical skills.
Exploring Brilliant Blue FCF Assembly with Beta Cyclodextrin, Characterizations and Applications in Biological Systems Using Physicochemical and Computational Methods
Authors: Saha Baishali , Barman Sanjoy , Mondal Modhusudan , Choudhury Subhankar , Saha Subhadeep , Bomzan Pranish , Ali Salim , Mallick Kangkan , Dutta Ankita , Kumar Anoop , Bhattacharjee Sanyukta , Nath Roy Mahendra
Published: January 2024

This research delvedinto the BrilliantBlue FCF (BB) dye encapsulation within the nano hydrophobic cavity of β‐cyclodextrin (β‐CD) utilizing various spectroscopic and physicochemical techniques. Job's plot using UV‐visible and Fluorescence spectroscopy, surface tension, and conductance study confirmed 1 : 1 stoichiometry of theinclusion complex (BBIC).1H NMR and FT‐IR studies demonstrated the possible binding mode of BB into the β‐CD cavity, which wasin good agreement withthe DFT study. The degree of affinity of β‐CD for BB in the ground state and excited state were estimatedfromUV‐visible andFluorescence spectroscopy(binding constant=8113.9451 M−1and10199.563 M−1), andthe negative free binding energyshowedthe encapsulation process to bethermodynamically feasible. PXRD analysis and SEM image studies revealed the formation of the BBIC. After complexation with β‐CD, the photostability of BB was found to be enhanced. The interaction study of BB and BBIC with CT‐DNA revealed the sustained release of BB from the complex. Furthermore, neither BBICnor free BB exhibited a significant cytotoxic effect on the normal cell line HEK‐293. However, BBIC complex (IC50=6.15 μM) showed significant in vitrocytotoxic activity compared to pure BB (IC50=8.90 μM) towards cancer cell line A549.
An Efficient Synthesis and Characterization of Amine and Amide Derivatives of Ethyl 6‐(trifluoromethyl)nicotinate
Authors: Keesara Srinivasa Reddy , Bolla Ratnasekhar , Bharathkumar Hanumantharayappa , Varkolu Mohan
Published: January 2024

A new bioactive amine and amide derivatives of trifluoromethyl pyridine was produced with good yields from commercially accessible and inexpensive starting materials and characterized using 1HNMR, 13CNMR, and mass spectrum analysis. We prepared all the intermediates in gram scale, it will be viable for industrial production, because the compounds contain a bioactive core component, trifluoromethylpyridine, they will be useful in developing new insecticides with improved therapeutic action.
Enhancing the Performance of 2D Tin‐Based Pure Red Perovskite Light‐Emitting Diodes through the Synergistic Effect of Natural Antioxidants and Cyclic Molecular Additives
Authors: Chen Chiung‐Han , Yu Ming‐Hsuan , Wang Yen‐Yu , Tseng Yu‐Cheng , Chao I‐Hsiang , Ni I‐Chih , Lin Bi‐Hsuan , Lu Yu‐Jung , Chueh Chu‐Chen
Published: January 2024

Tin (Sn)‐based perovskites are being investigated in many optoelectronic applications given their similar valence electron configuration to that of lead‐based perovskites and the potential environmental hazards of lead‐based perovskites. However, the formation of high‐quality Sn‐based perovskite films faces several challenges, mainly due to the easy oxidation of Sn2+ to Sn4+ and the fast crystallization rate. Here, to develop an environmentally friendly process for Sn‐based perovskite fabrication, a series of natural antioxidants are studied as additives and ascorbic acid (VitC) is found to have a superior ability to inhibit the oxidation problem. A common cyclic molecule, 18‐Crown‐6, is further added as a second additive, which synergizes with VitC to significantly reduce the nonradiative recombination pathways in the PEA2SnI4 film. This synergistic effect greatly improves the performance of 2D red Sn‐based PeLED, with a maximum external quantum efficiency of 1.87% (≈9 times that of the pristine device), a purer color, and better bias stability. This work demonstrates the potential of the dual‐additive approach in enhancing the performance of 2D Sn‐based PeLEDs, while the use of these environmentally friendly additives contributes to their future sustainability.
Biomimetic Nanoplatform for Dual‐Targeted Clearance of Activated and Senescent Cancer‐Associated Fibroblasts to Improve Radiation Resistance in Breast Cancer
Authors: Jian Chen , Wu Tingting , Wang Lulu , Gao Chen , Fu Zhiwen , Zhang Qian , Shi Chen
Published: January 2024

Radiation resistance in breast cancer resulting in residual lesions or recurrence is a significant cause to radiotherapy failure. Cancer‐associated fibroblasts (CAFs) and radiotherapy‐induced senescent CAFs can further lead to radiation resistance and tumor immunosuppressive microenvironment. Here, an engineering cancer‐cell‐biomimetic nanoplatform is constructed for dual‐targeted clearance of CAFs as well as senescent CAFs. The nanoplatform is prepared by 4T1 cell membrane vesicles chimerized with FAP single‐chain fragment variable as the biomimetic shell for targeting of CAFs and senescent CAFs, and PLGA nanoparticles (NPs) co‐encapsulated with nintedanib and ABT‐263 as the core for clearance of CAFs and senescent CAFs, which are noted as FAP‐CAR‐CM@PLGA‐AB NPs. It is evidenced that FAP‐CAR‐CM@PLGA‐AB NPs directly suppressed the tumor‐promoting effect of senescent CAFs. It also exhibits prolonged blood circulation and enhanced tumor accumulation, dual‐cleared CAFs and senescent CAFs, improved radiation resistance in both acquired and patient‐derived radioresistant tumor cells, and effective antitumor effect with the tumor suppression rate of 86.7%. In addition, FAP‐CAR‐CM@PLGA‐AB NPs reverse the tumor immunosuppressive microenvironment and enhance systemic antitumor immunity. The biomimetic system for dual‐targeted clearance of CAFs and senescent CAFs provides a potential strategy for enhancing the radio‐sensitization of breast cancer.
A low‐voltage‐driven, neuromorphic sensorimotor loop for monolithic soft prosthetic e‐skin
Authors: Li Xiangxiang , Mehvish Darakhshan , Yang Hui
Published: January 2024

Artificial skin with tactile perceptions is anticipated to play a pivotal role in next‐generation robotic and medical devices. The primary challenge lies in creating a biomimetic system that seamlessly integrates with the human body and biological systems. The authors have developed an electronic skin (e‐skin) that imitates the biological sensorimotor loop through medium‐scale circuit integration, boasting low power consumption and solid‐state synaptic transistors.
Lead‐Free All‐Inorganic Cesium Bismuth Iodide‐Based Perovskite Solar Cells: Recent Advances, Current Limitations, and Future Prospects
Authors: Li Shuang , He Jingsheng , Ran Ran , Zhou Wei , Wang Wei , Shao Zongping
Published: January 2024

Remarkable achievements have been made in the development of perovskite solar cells (PSCs) with a rapidly boosting rate of power conversion efficiencies (PCEs) from 3.8% to 26.1%. Nevertheless, the toxicity of lead (Pb) elements and the hygroscopicity of organic cations in high‐efficiency PSCs severely hamper the commercialization of this technology. Consequently, Pb‐free all‐inorganic PSCs have received increasing attention recently to resolve the above‐mentioned toxicity and instability problems. Among various Pb‐free all‐inorganic halide perovskites, cesium bismuth iodide (CBI)‐based perovskites have gained particular attention as light absorbers in PSCs due to the tunable/small bandgaps, long carrier diffusion length/lifetime, and superb sunlight absorption coefficients. Nevertheless, the PCEs of CBI‐based PSCs are still far away from Pb‐based organic–inorganic counterparts because of the low structural dimensions and inferior perovskite film quality. Herein, the recent advances of CBI‐based perovskites as light‐absorbing materials in Pb‐free all‐inorganic PSCs are reviewed by emphasizing the distinct structural/optical/electronic properties and currently existing limitations. Additionally, several distinct strategies to boost the PCEs and robusticity of CBI‐based PSCs are presented. Finally, the unsolved key problems and future directions of CBI‐based PSCs are proposed, aiming to provide important insights for the further development of CBI‐based PSCs to realize sustainable, nontoxic, high‐performance perovskite photovoltaics.
Porous Magnesium Hydride Nanoparticles Uniformly Coated by Mg‐Based Composites toward Advanced Lithium Storage Performance
Authors: Gao Panyu , Ju Shunlong , Huang Yuqin , Xia Guanglin , Sun Dalin , Yu Xuebin
Published: January 2024

Magnesium hydride (MgH2) has been recognized as a promising anode material of lithium‐ion batteries (LIBs) owing to its ultrahigh specific capacity. The low conductivity and the structural pulverization induced by large volume expansion, however, has long limited its practical lithium storage performance. Herein, a series of yolk‐shell‐like structures, composed of porous MgH2 nanoparticles (NPs) decorated with Mg‐based composites through in‐situ solid‐gas reaction using MgH2 as both the reactant and the structural template, have been fabricated and uniformly dispersed on electronically conductive graphene. It could not only physically accommodate the volume change of MgH2 owing to the physical protection of Mg‐based composites and the formation of void space inside MgH2 NPs, but also effectively facilitate the transportation of electrons throughout the whole electrode. Particularly, the uniform decoration of ultrathin Mg(BH4)2 as the shell with thermodynamically favorable intercalation of lithium ions and low kinetic barrier for the lithium‐ion diffusion promotes facile transportation of lithium ions into active MgH2, which, coupled with the porous structure constructed by flexible graphene, effectively improves the ion conductivity of the electrode. The synergistic improvement in electronic and ionic conductivity leads to a high reversible capacity of 1651 mAh g−1 at 200 mA g−1 after 380 cycles.
Shaping the future of men's sexual health: How artificial intelligence can assist in the management and treatment of erectile dysfunction
Authors: Sanchez Darren , Slovacek Hannah , Wang Run
Published: January 2024

Artificial intelligence (AI) is a complex combination of multidisciplinary machines and systems that can replicate human‐like cognitive tasks to execute capabilities such as pattern recognition, decision‐making, and problem‐solving. Dating back to the 2000s, AI has been utilized in the medical field, however the interest in this subject has sharply increased over the past several years. Erectile dysfunction (ED) is an increasingly pervasive issue as men age, affecting up to 150 million men worldwide. In the field of men's health, AI has been employed to assist physicians in the evaluation and management of ED. This article aims to summarize the ways in which AI has been utilized in the management of ED, as well as the considerations that must be made when implementing this technology. AI can be utilized for virtual health assistance to protect patient privacy and increase access to care. Augmented reality can aid surgeons in real‐time during operations, as well as be utilized to prepare physicians for situations that they may encounter in the operating room. Pharmaceutical companies can benefit from AI in the interpretation of data, analysis of chemical compounds and in drug development. Additionally, AI can be used to assist patients in post‐procedure recovery in the form of rehabilitation and post‐treatment monitoring. While the utilization of AI in men's health is an exciting venture, there are tremendous ethical and practical considerations that have limited its use in the management of ED.
Modular Hamiltonian in the semi infinite line. Part II. Dimensional reduction of Dirac fermions in spherically symmetric regions
Authors: Huerta Marina , van der Velde Guido
Published: January 2024

Abstract

In this article, we extend our study on a new class of modular Hamiltonians on an interval attached to the origin on the semi-infinite line, introduced in a recent work dedicated to scalar fields. Here, we shift our attention to fermions and similarly to the scalar case, we investigate the modular Hamiltonians of theories which are obtained through dimensional reduction, this time, of a free massless Dirac field in d dimensions. By following the same methodology, we perform dimensional reduction on both the physical and modular Hamiltonians. This process enables us to establish a correspondence: we identify the modular Hamiltonian in an interval connected to the origin to the one obtained from the reduction of the modular Hamiltonian pertaining to the conformal parent theory on a sphere. Intriguingly, although the resulting one-dimensional theories lack conformal symmetry due to the presence of a term proportional to 1/r, the corresponding modular Hamiltonians are local functions in the energy density. This phenomenon mirrors the well known behaviour observed in the conformal case and indicates the existence of a residual symmetry, characterized by a subset of the original conformal group.

Furthermore, through an analysis of the spectrum of the modular Hamiltonians, we derive an analytic expression for the associated entanglement entropy. Our findings also enable us to successfully recover the conformal anomaly coefficient from the universal piece of the entropy in even dimensions, as well as the universal constant F term in d = 3, by extending the radial regularization scheme originally introduced by Srednicki to perform the sum over angular modes.
Knockdown of NEAT1 prevents post-stroke lipid droplet agglomeration in microglia by regulating autophagy
Authors: Pan Yongli , Xin Wenqiang , Wei Wei , Tatenhorst Lars , Graf Irina , Popa-Wagner Aurel , Gerner Stefan T. , Huber Sabine E. , Kilic Ertugrul , Hermann Dirk M. , Bähr Mathias , Huttner Hagen B. , Doeppner Thorsten R.
Published: January 2024

Background

Lipid droplets (LD), lipid-storing organelles containing neutral lipids like glycerolipids and cholesterol, are increasingly accepted as hallmarks of inflammation. The nuclear paraspeckle assembly transcript 1 (NEAT1), a long non-coding RNA with over 200 nucleotides, exerts an indispensable impact on regulating both LD agglomeration and autophagy in multiple neurological disorders. However, knowledge as to how NEAT1 modulates the formation of LD and associated signaling pathways is limited.

Methods

In this study, primary microglia were isolated from newborn mice and exposed to oxygen-glucose-deprivation/reoxygenation (OGD/R). To further explore NEAT1-dependent mechanisms, an antisense oligonucleotide (ASO) was adopted to silence NEAT1 under in vitro conditions. Studying NEAT1-dependent interactions with regard to autophagy and LD agglomeration under hypoxic conditions, the inhibitor and activator of autophagy 3-methyladenine (3-MA) and rapamycin (RAPA) were used, respectively. In a preclinical stroke model, mice received intraventricular injections of ASO NEAT1 or control vectors in order to yield NEAT1 knockdown. Analysis of readout parameters included qRT-PCR, immunofluorescence, western blot assays, and behavioral tests.

Results

Microglia exposed to OGD/R displayed a temporal pattern of NEAT1 expression, peaking at four hours of hypoxia followed by six hours of reoxygenation. After effectively silencing NEAT1, LD formation and autophagy-related proteins were significantly repressed in hypoxic microglia. Stimulating autophagy in ASO NEAT1 microglia under OGD/R conditions by means of RAPA reversed the downregulation of LD agglomeration and perilipin 2 (PLIN2) expression. On the contrary, application of 3-MA promoted repression of both LD agglomeration and expression of the LD-associated protein PLIN2. Under in vivo conditions, NEAT1 was significantly increased in mice at 24 h post-stroke. Knockdown of NEAT1 significantly alleviated LD agglomeration and inhibited autophagy, resulting in improved cerebral perfusion, reduced brain injury and increased neurological recovery.

Conclusion

NEAT1 is a key player of LD agglomeration and autophagy stimulation, and NEAT1 knockdown provides a promising therapeutic value against stroke.

Graphical abstract
Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction
Authors: LeFort Karli R. , Rungratanawanich Wiramon , Song Byoung-Joon
Published: January 2024

This review provides an update on recent findings from basic, translational, and clinical studies on the molecular mechanisms of mitochondrial dysfunction and apoptosis of hepatocytes in multiple liver diseases, including but not limited to alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), and drug-induced liver injury (DILI). While the ethanol-inducible cytochrome P450-2E1 (CYP2E1) is mainly responsible for oxidizing binge alcohol via the microsomal ethanol oxidizing system, it is also responsible for metabolizing many xenobiotics, including pollutants, chemicals, drugs, and specific diets abundant in n-6 fatty acids, into toxic metabolites in many organs, including the liver, causing pathological insults through organelles such as mitochondria and endoplasmic reticula. Oxidative imbalances (oxidative stress) in mitochondria promote the covalent modifications of lipids, proteins, and nucleic acids through enzymatic and non-enzymatic mechanisms. Excessive changes stimulate various post-translational modifications (PTMs) of mitochondrial proteins, transcription factors, and histones. Increased PTMs of mitochondrial proteins inactivate many enzymes involved in the reduction of oxidative species, fatty acid metabolism, and mitophagy pathways, leading to mitochondrial dysfunction, energy depletion, and apoptosis. Unique from other organelles, mitochondria control many signaling cascades involved in bioenergetics (fat metabolism), inflammation, and apoptosis/necrosis of hepatocytes. When mitochondrial homeostasis is shifted, these pathways become altered or shut down, likely contributing to the death of hepatocytes with activation of inflammation and hepatic stellate cells, causing liver fibrosis and cirrhosis. This review will encapsulate how mitochondrial dysfunction contributes to hepatocyte apoptosis in several types of liver diseases in order to provide recommendations for targeted therapeutics.
Disease-associated nonsense and frame-shift variants resulting in the truncation of the GluN2A or GluN2B C-terminal domain decrease NMDAR surface expression and reduce potentiating effects of neurosteroids
Authors: Kysilov Bohdan , Kuchtiak Viktor , Hrcka Krausova Barbora , Balik Ales , Korinek Miloslav , Fili Klevinda , Dobrovolski Mark , Abramova Vera , Chodounska Hana , Kudova Eva , Bozikova Paulina , Cerny Jiri , Smejkalova Tereza , Vyklicky Ladislav
Published: January 2024

N-methyl-d-aspartate receptors (NMDARs) play a critical role in normal brain function, and variants in genes encoding NMDAR subunits have been described in individuals with various neuropsychiatric disorders. We have used whole-cell patch-clamp electrophysiology, fluorescence microscopy and in-silico modeling to explore the functional consequences of disease-associated nonsense and frame-shift variants resulting in the truncation of GluN2A or GluN2B C-terminal domain (CTD). This study characterizes variant NMDARs and shows their reduced surface expression and synaptic localization, altered agonist affinity, increased desensitization, and reduced probability of channel opening. We also show that naturally occurring and synthetic steroids pregnenolone sulfate and epipregnanolone butanoic acid, respectively, enhance NMDAR function in a way that is dependent on the length of the truncated CTD and, further, is steroid-specific, GluN2A/B subunit-specific, and GluN1 splice variant-specific. Adding to the previously described effects of disease-associated NMDAR variants on the receptor biogenesis and function, our results improve the understanding of the molecular consequences of NMDAR CTD truncations and provide an opportunity for the development of new therapeutic neurosteroid-based ligands.
Progression of type 1 diabetes is associated with high levels of soluble PD-1 in islet autoantibody-positive children
Authors: Bruzzaniti Sara , Piemonte Erica , Bruzzese Dario , Lepore Maria Teresa , Strollo Rocky , Izzo Lavinia , Di Candia Francesca , Franzese Adriana , Bifulco Maurizio , Mozzillo Enza , Ludvigsson Johnny , Matarese Giuseppe , Galgani Mario
Published: January 2024

Aims/hypothesis

Type 1 diabetes is an autoimmune disorder that is characterised by destruction of pancreatic beta cells by autoreactive T lymphocytes. Although islet autoantibodies (AAb) are an indicator of disease progression, specific immune biomarkers that can be used as target molecules to halt development of type 1 diabetes have not been discovered. Soluble immune checkpoint molecules (sICM) play a pivotal role in counteracting excessive lymphocyte responses, but their role in type 1 diabetes is unexplored. In this longitudinal study, we measured sICM levels in AAb-positive (AAb+) children to identify molecules related to type 1 diabetes progression.

Methods

We measured the levels of 14 sICM in the sera of AAb+ children (n=57) compared to those with recent-onset type 1 diabetes (n=79) and healthy children (n=44), obtained from two cohorts. AAb+ children were followed up and divided based on their progression to type 1 diabetes (AAbP) or not (AAbNP) (if they lost islet autoimmunity and did not develop disease in subsequent years). sICM were also measured in the sample taken at the visit closest to disease onset in AAbP children.

Results

We found that AAb+ children had a distinct sICM profile compared with healthy children and those with recent-onset type 1 diabetes. In addition, AAb+ children who progressed to type 1 diabetes (AAbP) had higher sICM concentrations than non-progressors (AAbNP). Further, sICM levels decreased in AAbP children close to disease onset. Application of Cox regression models highlighted that high concentrations of soluble programmed cell death protein 1 (sPD-1) are associated with type 1 diabetes progression (HR 1.71; 95% CI 1.16, 2.51; p=0.007).

Conclusions/interpretation

This study reveals an sICM profile that is dysregulated during the preclinical stage of type 1 diabetes, and identifies sPD-1 as a pathophysiologically-relevant molecule that is associated with disease progression, offering a potential target for early interventions in autoimmune diabetes.

Graphical Abstract
Nanosponge hydrogel of octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate of Alcaligenes faecalis
Authors: El-Sayed Sayed E. , Abdelaziz Neveen A. , El-Housseiny Ghadir S. , Aboshanab Khaled M.
Published: January 2024

Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate (ODHP) was extracted in a previous study from the culture broth of soil isolate Alcaligenes faecalis MT332429 and showed a promising antimycotic activity. This study was aimed to formulate ODHP loaded β-cyclodextrins (CD) nanosponge (NS) hydrogel (HG) to control skin fungal ailments since nanosponges augment the retention of tested agents in the skin. Box-Behnken design was used to produce the optimized NS formulation, where entrapment efficiency percent (EE%), polydispersity index (PDI), and particle size (PS) were assigned as dependent parameters, while the independent process parameters were polyvinyl alcohol % (w/v %), polymer-linker ratio, homogenization time, and speed. The carbopol 940 hydrogel was then created by incorporating the nanosponges. The hydrogel fit Higuchi’s kinetic release model the best, according to in vitro drug release. Stability and photodegradation studies revealed that the NS-HG remained stable under tested conditions. The formulation also showed higher in vitro antifungal activity against Candida albicans compared to the control fluconazole. In vivo study showed that ODHP-NS-HG increased survival rates, wound contraction, and healing of wound gap and inhibited the inflammation process compared to the other control groups. The histopathological examinations and Masson’s trichrome staining showed improved healing and higher records of collagen deposition. Moreover, the permeability of ODHP-NS-HG was higher through rats’ skin by 1.5-folds compared to the control isoconazole 1%. Therefore, based on these results, NS-HG formulation is a potential carrier for enhanced and improved topical delivery of ODHP. Our study is a pioneering research on the development of a formulation for ODHP produced naturally from soil bacteria.

Key points

• Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propanoate was successfully formulated as a nanosponge hydrogel and statistically optimized.

• The new formula exhibited in vitro good stability, drug release, and higher antifungal activity against C. albicans as compared to the fluconazole.

• Ex vivo showed enhanced skin permeability, and in vivo analysis showed high antifungal activity as evidenced by measurement of various biochemical parameters and histopathological examination.