bluuebunny/crossref_metadata_2025 huggingface dataset:
A Fully Biodegradable and Ultra‐Sensitive Crack‐Based Strain Sensor for Biomechanical Signal Monitoring
Authors: Lee Jae‐Hwan , Bae Jae‐Young , Kim Yoon‐Nam , Chae Minseong , Lee Woo‐Jin , Lee Junsang , Kim Im‐Deok , Hyun Jung Keun , Lee Kang‐Sik , Kang Daeshik , Kang Seung‐Kyun
Published: July 2024

A fully biodegradable, ultra‐sensitive, and soft strain sensor is pivotal for temporary, real‐time monitoring of microdeformations, crucial in disease diagnosis, surgical precision, and prognosis of muscular, and vascular conditions. Nevertheless, the strain sensitivity of previous biodegradable sensors, denoted by gauge factor (GF) up to ≈100, falls short of requirements for complex biomedical monitoring scenarios, specifically monitoring cardio‐cerebrovascular diseases with microscale variations in vascular surface strain. Here, a fully biodegradable, ultra‐sensitive crack‐based flexible strain sensor is introduced achieving GF of 1355 at 1.5% strain through integration of molybdenum (Mo) film, molybdenum trioxide (MoO3) adhesion layer, and polycaprolactone (PCL) substrate. Analysis of crack morphology of biodegradable thin‐film metals, including Mo, tungsten (W), and magnesium (Mg), reveals material‐dependent sensitivity and repeatability of crack‐based strain sensors. The effect of the adhesion layer and polymer substrate is also investigated. Overall morphological studies on the sensor present a comprehensive understanding of metal film cracking behavior and corresponding performance characterization, showing significant potential for highly sensitive sensors. A hybrid membrane composed of candelilla wax (Cw), beeswax (Bw), and polybutylene adipate‐co‐terephthalate (PBAT) is introduced to provide hydrophobic, yet flexible encapsulation. In vivo, short‐term (≈3 days) monitoring of vascular pulsatility underscores the potential of the sensing tool for rapid, accurate, and temporal disease diagnosis and treatment.
Redox‐Responsive Hydrogels Loaded with an Antibacterial Peptide as Controlled Drug Delivery for Healing Infectious Wounds
Authors: Cherri Mariam , Stergiou Paraskevi S. , Ahmadian Zainab , Povolotsky Tatyana L. , Thongrom Boonya , Fan Xin , Mohammadifar Ehsan , Haag Rainer
Published: July 2024

Infectious wounds occur when harmful microorganisms such as bacteria or viruses invade a wound site. Its problems associated include delayed healing, increased pain, swelling, and the potential for systemic infections. Therefore, developing new wound dressing materials with antibacterial effects is crucial for improving the healing process. Here a redox‐degradable hydrogel loaded with an antibacterial peptide (vancomycin) in a straightforward gram‐scale synthesis, is developed. The hydrogel structure consists of a disulfide bond‐containing hyperbranched polyglycerol (SS‐hPG) that is cross‐linked by 4‐arm polyethylene glycol‐thiol (4‐arm PEG‐SH). The polymerization mechanism and full characterization of SS‐hPG are described as this synthesis is reported for the first time. Rheology is used to ascertain the hydrogel's mechanical characteristics, such as stiffness, and self‐healing, determining these properties for different ratios and concentrations of both gel components. The incorporation of disulfide bonds in the hydrogel is proved by conducting degradation experiments in reductive environments. Fluorescein isothiocyanate‐albumin (FITC‐BSA) and vancomycin both are loaded into the gel, and the guest release kinetics is assessed for both slow and on‐demand releases. Finally, the in vitro and in vivo experiments prove that the vancomycin‐loaded hydrogel acts as an antibacterial barrier for wound dressing and accelerates the healing of infectious wounds in a mouse model.
Electronic Performance and Schottky Contact of 2D GeH/InSe and GeH/In2Se3 Heterostructures: Strain Engineering and Electric Field Tunability
Authors: Bafekry Asadollah , Karbasizadeh Siavash , Faraji Mehrdad , Jappor Hamad Rahman , Ziabari Ali Abdolahzadeh , Fadlallah Mohamed M. , Ghergherehchi Mitra , Chang Gap Soo
Published: July 2024

Recent exciting developments in synthesis and properties study of the germanane (GeH) mono‐layer have inspired us to investigate the structural and electronic properties of the van der Waals heterostructures (HTS) of GeH/InSe and GeH/In2Se3 through a first‐principles methodology. In this study, structural and electronic properties of the HTS are examined thoroughly. GeH/InSe and GeH/In2Se3 are determined as n‐type Schottky with a Schottky barrier height (SBH) of 0.40 eV and n‐type ohmic, respectively. GeH/InSe turns out as a semiconductor with a direct bandgap of 0.62 eV, while GeH/In2Se3 is seen to be a metal. The results show that changing of the bandgap and SBH in very small values. For GeH/In2Se3 the effects are even less substantial, as the metallic or n‐type nature of the material does not change. The biaxial strain and electric field have more tangible effects on the characteristics of the HTS. A mixture of compressive and tensile strain is seen to have the capability of changing GeH/InSe into a metal and at the same time transform it to an n‐type/p‐type ohmic or p‐type Schottky contact. The results given here can guide future research in the field of HTS and especially GeH‐based devices.
Microglia Gravitate toward Amyloid Plaques Surrounded by Externalized Phosphatidylserine via TREM2
Authors: Park Jong‐Chan , Han Jong Won , Lee Woochan , Kim Jieun , Lee Sang‐Eun , Lee Dongjoon , Choi Hayoung , Han Jihui , Kang You Jung , Diep Yen N. , Cho Hansang , Kang Rian , Yu Won Jong , Lee Jean , Choi Murim , Im Sun‐Wha , Kim Jong‐Il , Mook‐Jung Inhee
Published: July 2024

Microglia play a crucial role in synaptic elimination by engulfing dystrophic neurons via triggering receptors expressed on myeloid cells 2 (TREM2). They are also involved in the clearance of beta‐amyloid (Aβ) plaques in Alzheimer's disease (AD); nonetheless, the driving force behind TREM2‐mediated phagocytosis of beta‐amyloid (Aβ) plaques remains unknown. Here, using advanced 2D/3D/4D co‐culture systems with loss‐of‐function mutations in TREM2 (a frameshift mutation engineered in exon 2) brain organoids/microglia/assembloids, it is identified that the clearance of Aβ via TREM2 is accelerated by externalized phosphatidylserine (ePtdSer) generated from dystrophic neurons surrounding the Aβ plaques. Moreover, it is investigated whether microglia from both sporadic (CRISPR‐Cas9‐based APOE4 lines) and familial (APPNL‐G‐F/MAPT double knock‐in mice) AD models show reduced levels of TREM2 and lack of phagocytic activity toward ePtdSer‐positive Aβ plaques. Herein new insight is provided into TREM2‐dependent microglial phagocytosis of Aβ plaques in the context of the presence of ePtdSer during AD progression.
Blood Brain Barrier‐Crossing Delivery of Felodipine Nanodrug Ameliorates Anxiety‐Like Behavior and Cognitive Impairment in Alzheimer's Disease
Authors: He Xiaofei , Peng Yuan , Huang Sicong , Xiao Zecong , Li Ge , Zuo Zejie , Zhang Liying , Shuai Xintao , Zheng Haiqing , Hu Xiquan
Published: July 2024

Alzheimer's disease (AD) is the most common age‐related neurodegenerative disorder leading to cognitive decline. Excessive cytosolic calcium (Ca2+) accumulation plays a critical role in the pathogenesis of AD since it activates the NOD‐like receptor family, pyrin domain containing 3 (NLRP3), switches the endoplasmic reticulum (ER) unfolded protein response (UPR) toward proapoptotic signaling and promotes Aβ seeding. Herein, a liposomal nanodrug (felodipine@LND) is developed incorporating a calcium channel antagonist felodipine for Alzheimer's disease treatment through a low‐intensity pulse ultrasound (LIPUS) irradiation‐assisted blood brain barrier (BBB)‐crossing drug delivery. The multifunctional felodipine@LND is effectively delivered to diseased brain through applying a LIPUS irradiation to the skull, which resulted in a series of positive effects against AD. Markedly, the nanodrug treatment switched the ER UPR toward antioxidant signaling, prevented the surface translocation of ER calreticulin (CALR) in microglia, and inhibited the NLRP3 activation and Aβ seeding. In addition, it promoted the degradation of damaged mitochondria via mitophagy, thereby inhibiting the neuronal apoptosis. Therefore, the anxiety‐like behavior and cognitive impairment of 5xFAD mice with AD is significantly ameliorated, which manifested the potential of LIPUS – assisted BBB‐crossing delivery of felodipine@LND to serve as a paradigm for AD therapy based on the well‐recognized clinically available felodipine.
Stabilization of TGF‐β Receptor 1 by a Receptor‐Associated Adaptor Dictates Feedback Activation of the TGF‐β Signaling Pathway to Maintain Liver Cancer Stemness and Drug Resistance
Authors: Liu Kewei , Tian Fanxuan , Chen Xu , Liu Biyin , Tian Shuoran , Hou Yongying , Wang Lei , Han Mengyi , Peng Shiying , Tan Yuting , Pan Yuwei , Chu Zhaole , Li Jinyang , Che Linrong , Chen Dongfeng , Wen Liangzhi , Qin Zhongyi , Li Xianfeng , Xiang Junyu , Bian Xiu‐wu , Liu Qin , Ye Xiaoli , Wang Tao , Wang Bin
Published: July 2024

Dysregulation of the transforming growth factor‐β (TGF‐β) signaling pathway regulates cancer stem cells (CSCs) and drug sensitivity, whereas it remains largely unknown how feedback regulatory mechanisms are hijacked to fuel drug‐resistant CSCs. Through a genome‐wide CRISPR activation screen utilizing stem‐like drug‐resistant properties as a readout, the TGF‐β receptor‐associated binding protein 1 (TGFBRAP1) is identified as a TGF‐β‐inducible positive feedback regulator that governs sensitivity to tyrosine kinase inhibitors (TKIs) and promotes liver cancer stemness. By interacting with and stabilizing the TGF‐β receptor type 1 (TGFBR1), TGFBRAP1 plays an important role in potentiating TGF‐β signaling. Mechanistically, TGFBRAP1 competes with E3 ubiquitin ligases Smurf1/2 for binding to TGFΒR1, leading to impaired receptor poly‐ubiquitination and proteasomal degradation. Moreover, hyperactive TGF‐β signaling in turn up‐regulates TGFBRAP1 expression in drug‐resistant CSC‐like cells, thereby constituting a previously uncharacterized feedback mechanism to amplify TGF‐β signaling. As such, TGFBRAP1 expression is correlated with TGFΒR1 levels and TGF‐β signaling activity in hepatocellular carcinoma (HCC) tissues, as well as overall survival and disease recurrence in multiple HCC cohorts. Therapeutically, blocking TGFBRAP1‐mediated stabilization of TGFBR1 by selective inhibitors alleviates Regorafenib resistance via reducing CSCs. Collectively, targeting feedback machinery of TGF‐β signaling pathway may be an actionable approach to mitigate drug resistance and liver cancer stemness.
A Microenvironment‐Responsive, Controlled Release Hydrogel Delivering Embelin to Promote Bone Repair of Periodontitis via Anti‐Infection and Osteo‐Immune Modulation
Authors: Cai Guanming , Ren Lin , Yu Jiali , Jiang Siqi , Liu Gen , Wu Shujie , Cheng Bin , Li Weichang , Xia Juan
Published: July 2024

Periodontitis, a prevalent chronic inflammatory disease, poses significant challenges for effective treatment due to its complex etiology involving specific bacteria and the inflammatory immune microenvironment. Here, this study presents a novel approach for the targeted treatment of periodontitis utilizing the immunomodulatory and antibacterial properties of Embelin, a plant‐derived compound, within an injectable hydrogel system. The developed Carboxymethyl Chitosan‐Oxidized Dextran (CMCS‐OD) hydrogel formed via dynamic chemical bonds exhibited self‐healing capabilities and pH‐responsive behavior, thereby facilitating the controlled release of Embelin and enhancing its efficacy in a dynamic oral periodontitis microenvironment. This study demonstrates that this hydrogel system effectively prevents bacterial invasion and mitigates excessive immune response activation. Moreover, it precisely modulates macrophage M1/M2 phenotypes and suppresses inflammatory cytokine expression, thereby fostering a conducive environment for bone regeneration and addressing periodontitis‐induced bone loss. These findings highlight the potential of the approach as a promising strategy for the clinical management of periodontitis‐induced bone destruction.
Stretching, Tapping, or Compressing–What Role Does Triboelectricity Play in the Signal Output from Piezoelectric Nanogenerators?
Authors: Akbarinejad Alireza , Fiedler Holger , Nguyen Jade , Li Zifan , Gito Donn Adam , Sherrell Peter C. , Ellis Amanda V. , Aw Kean , Malmstrom Jenny
Published: July 2024

Piezoelectric energy generation is relevant for developing advanced electronics. However, the poor understanding of the influence of triboelectricity as an alternate charge generation mechanism has, in many cases, resulted in the reporting of exaggerated piezoelectric outputs. Herein, the signal output is systematically investigated from a range of organic piezoelectric materials (poled polyvinylidene fluoride (PVDF)), moderately piezoelectric (heat‐treated PVDF), and non‐piezoelectric (non‐poled PVDF), polytetrafluoroelthylene (Teflon) and nylon) under tapping and compression (33 direction) and stretching (31 direction) in both encapsulated and non‐encapsulated forms. This findings reveal that regardless of their piezoelectric properties, all tested materials exhibit substantial voltage outputs (4.2–4.6 V) during tapping, primarily attributed to the triboelectric effect at the contact interface. The triboelectric contribution to the signal is reduced by 99% in compression mode for non‐piezoelectric materials and the piezoelectric signal is the primary contributor in the stretching mode with a high signal output of 7.71 V N−1 for poled PVDF and a negligible signal (0.01–0.12 V N−1) for non‐piezoelectric materials. Moreover, elastomeric encapsulation is demonstrated to markedly increase triboelectric signals in tapping mode. These results have important implications for the future design of piezoelectric‐triboelectric devices and the accurate interpretation of the data obtained from such devices.
Silicon‐Inspired Analysis of Interfacial Recombination in Perovskite Photovoltaics
Authors: Gillespie Sarah C. , Gautier Jérôme , van der Burgt Julia S. , Anker John , Geerligs Bart L.J. , Coletti Gianluca , Garnett Erik C.
Published: July 2024

Perovskite solar cells have reached an impressive certified efficiency of 26.1%, with a considerable fraction of the remaining losses attributed to carrier recombination at perovskite interfaces. This work demonstrates how time‐resolved photoluminescence spectroscopy (TRPL) can be utilized to locate and quantify remaining recombination losses in perovskite solar cells, analogous to methods established to improve silicon solar cell passivation and contact layers. It is shown how TRPL analysis can be extended to determine the bulk and surface lifetimes, surface recombination velocity, the recombination parameter, J0, and the implied open‐circuit voltage (iVoc) of any perovskite device configuration. This framework is used to compare 18 carrier‐selective and passivating contacts commonly used or emerging for perovskite photovoltaics. Furthermore, the iVoc values calculated from the TRPL‐based framework are directly compared to those calculated from photoluminescence quantum yields and the measured solar cell Voc. This simple technique serves as a practical guide for screening and selecting multifunctional, passivating perovskite contact layers. As with silicon solar cells, most of the material and interface analysis can be done without fabricating full devices or measuring efficiency. These purely optical measurements are even preferable when studying bulk and interfacial passivation approaches, since they remove complicating effects from poor carrier extraction.
DNA nanomachine‐driven chemodynamic therapy against glioblastoma
Authors: Li Xiaodie , Lan Yufei , Fu Xin , Luo Xin , Chen Jie , Zhang Wenxin , Zuo Boming , Yang Tao , Liu Boyang , Zhang Chao , Guo Hongbo
Published: July 2024

Chemodynamic therapy (CDT) has shown promising antitumor effects in various malignant tumors. However, its application for glioblastoma (GBM) is significantly hindered by the challenge of delivering CDT agents across the blood‐brain barrier (BBB) and achieving efficient tumor targeting. To overcome these obstacles, this study presents a novel DNA nanomachine (Cu@tFNAs‐G‐A NM) by loading copper ions (Cu2+) onto tetrahedral framework nucleic acids (tFNAs) functionalized with dual DNA aptamers. The dual DNA aptamers (GS24 for BBB penetration and AS1411 for tumor targeting) empowered Cu@tFNAs‐G‐A NM with the ability to effectively penetrate the BBB and selectively accumulate in tumor cells. Upon internalization, the loaded Cu2+ reacted with tumor‐overexpressed reductive glutathione (GSH) and hydrogen peroxide (H2O2), generating hydroxyl radicals (·OH) and inducing tumor cell death. Additionally, Cu@tFNAs‐G‐A NM was found to be rapidly cleared from the brain and normal tissues within 24 h, minimizing potential systemic toxic side effects. These findings demonstrate the promising potential of Cu@tFNAs‐G‐A NM for effective CDT against GBM and open up new avenues for the development of targeted therapies for GBM.
Safety and efficacy of baricitinib in steroid‐resistant or relapsed immune thrombocytopenia: An open‐label pilot study
Authors: Zhao Peng , An Zhuo‐Yu , Fu Hai‐Xia , Liu Hui‐Xin , Feng Cheng‐Jie , Huang Qiu‐Sha , Wu Jin , Wu Ye‐Jun , Yang Li‐Ping , Qu Qing‐Yuan , Chen Yu‐Xiu , Li Meng‐Lin , Wang Chen‐Cong , Chen Qi , Zhu Xiao‐Lu , He Yun , Zhang Yuan‐Yuan , Jiang Qian , Jiang Hao , Lu Jin , Chang Ying‐Jun , Zhao Xiao‐Su , Zhao Xiang‐Yu , Huang Xiao‐Jun , Zhang Xiao‐Hui
Published: July 2024

Patients with steroid‐resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus‐associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open‐label, single‐arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6‐month follow‐up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6–20) days, and the median peak platelet count was 94 (IQR 72–128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP‐modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.
Population expansion, larger, and more homogeneous native American ancestry among Mexican mestizo populations based on 10 X‐chromosome STR loci (X‐STR decaplex system)
Authors: Mariscal‐Ramos Christian , Cortes‐Trujllo Irán , Martínez‐Cortés Gabriela , Arana Ismael Nuño , Rangel‐Villalobos Héctor
Published: July 2024

Objective

To evaluate the genetic diversity, admixture, genetic relationships, and sex‐biased demographic processes in Mexican Mestizo (admixed) populations based on 10 X‐chromosome STRs (X‐STRs).

Methods

We analyzed the X‐STRs Decaplex system in 104 Mexican Native Americans to obtain the ancestral reference needed to complete the demographic analyses above mentioned. We included reported Iberian and Latin American (admixed) populations from Central and South America, as well as datasets from Mexican Mestizos based on Y‐linked STRs (Y‐STRs), autosomal STRs (A‐STRs), and mtDNA.

Results

Higher X‐linked Native American ancestry was observed among Latin American populations regarding that reported from A‐STRs and Y‐STRs. The interpopulation differentiation based on ancestry among Mexican Mestizos diminished according to the inheritance pattern: Y‐STRs (highest), A‐STRs, X‐STRs, and mtDNA (lowest). This finding is related to the peculiar admixture process that occurred during and after the Spanish Conquest of Mexico (and most of Latin America), involving a large number of Spanish men (Y‐chromosomes) with a lesser proportion of X‐chromosomes than autosomes; besides to the limited number of Spanish women (XX) arrived in the Americas in subsequent and shorter periods. Population expansion was detected in Mexican Mestizos from all the country, except those from the southeast region characterized by elevated indigenous ancestry, marginalization, and poorness.

Conclusions

Population growth was detected in most Mexican Mestizos, besides more homogeneous and larger Native American ancestry based on X‐linked inheritance than that based on autosomal STRs and Y‐STRs.
Bone density in postmenopausal women with scoliosis is associated with markers of degenerative joint disease
Authors: Ganji Elahe , Burshell Alan , Khicha Amisha , Lee Katharine M. N.
Published: July 2024

Purpose

Bone mineral density (BMD) measured with dual x‐ray absorptiometry (DXA) is the clinical standard for the diagnosis of osteoporosis and prediction of bone fracture risk. In the aging skeleton, osteoporosis is often concomitantly present with degenerative joint disease (DJD).

Methods

In this study, we evaluated tissue‐level changes in the differentially loaded concave (CC) and convex (CV) sides of the lumbar spine in a sample of postmenopausal women with scoliosis. We used a cumulative degeneration score to assess osteophyte formation, the severity of sclerotic morphology, and marrow changes as markers of DJD in the lumbar spine and examined the correlation between markers of DJD and BMD.

Results

More severe osteophyte growth and sclerosis were present on the CC side of the spine. The degenerative score (DS) was higher on the CC side of the lumbar spine compared with the CV side. While CC BMD was positively correlated with CC DS and marrow, CV DS was not correlated with CV BMD. Marrow changes were correlated with DS on the CC lumbar spine.

Conclusion

These results highlight the importance of mechanoadaptive as well as broader inflammatory processes in the manifestation of degenerative changes and local mineral deposition at the lumbar spine. DXA‐based BMD measurement of osteoporosis need to be contextualized within the biomechanical and degenerative conditions of a joint rather than using a strict threshold cutoff.
Comparison of internal and external reference populations for occupational cancer surveillance in a cohort drawn from a diverse workforce
Authors: Everest Louis , Tan Shirui , Navaneelan Tanya , Demers Paul A. , DeBono Nathan , Berriault Colin , Sritharan Jeavana
Published: July 2024

Objectives

Prior analyses of the Occupational Disease Surveillance System (ODSS) have compared cancer rates using internal referent groups. As an exploratory analysis, we sought to estimate cancer risk using general population reference rates to evaluate the impact that the comparison population has on findings from our surveillance program.

Methods

A cohort of approximately 2.3 million workers in Ontario, Canada with an accepted lost‐time workers' compensation claim were followed for all cancer diagnoses between 1983 and 2018. Standardized incidence ratios (SIRs) and 95% confidence intervals were calculated for workers in specific occupational groups using (1) all other workers in the ODSS cohort, and (2) the general population of Ontario.

Results

SIRs using the general population reference group were generally equal to or modestly lower compared to SIRs using the internal reference group. Within occupation groups, SIRs had a discordant direction of association (increased rate in the internal comparison and decreased in the external comparison) for some cancer sites including urinary, prostate, and colorectal.

Conclusions

Findings emphasize the importance of the choice of reference group when evaluating cancer risks in large occupational surveillance cohorts. Importantly, the magnitude of confounding and the healthy worker hire bias may depend on the occupation group and cancer site of interest.
Ultra‐high‐performance liquid chromatography‐quadrupole time‐of‐flight‐mass spectrometry‐characterized extract of Aerides odorata Lour alleviates paracetamol‐induced hepatotoxicity in animal model evidenced by biochemical, molecular, and computational studies
Authors: Ahmed A. M. Abu , Rahman Md. Atiar , Sharmen Farjana , Reza A. S. M. Ali , Islam Md. Shahidul , Rashid Md. Mamunur , Rafi Md. Khalid Juhani , Siddiqui Tanvir Ahmed , Ezaj Md. Muzahid Ahmed , Saha Srabonti , Uddin Md. Nazim , Alelwani Walla
Published: July 2024

Background

Many kinds of orchids have significant health benefits although adequate research on their biological functions is yet to be carried out. This study investigated the paracetamol‐induced liver damage–protecting effect of epiphytic Aerides odorata methanol extract (AODE).

Methods

The protective effects of AODE were studied by analyzing its effect on liver function parameters, messenger RNA (mRNA) expression, and tissue histopathological architecture. The results were confirmed by ligand–receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses.

Results

AODE significantly (p < 0.05) minimized the dose‐dependent increase in acid phosphatase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ‐glutamyl transferase, lactate dehydrogenase, and total bilirubin compared to the reference drug silymarin. Malondialdehyde level decreased, and the antioxidant genes catalase (CAT), superoxide dismutase (SOD), β‐actin, paraoxonase‐1 (PON1), and phosphofructokinase‐1 (PFK‐1) were upregulated in AODE‐treated paracetamol‐intoxicated rats. A total of 376 compounds comprising phenols and flavonoids were identified using ultra‐high‐performance liquid chromatography‐quadrupole time‐of‐flight‐mass spectrometry (UPLC‐qTOF‐MS). The online toxicity assessment using SwissADME and admetSAR exhibited drug‐like, nontoxic, and potential pharmacological properties. Additionally, in silico analysis showed that isoacteoside, one of the identified compounds, exhibited the best docking score (−11.42) with the liver protein human pituitary adenylate cyclase‐1 (Protein Data Bank ID: 3N94). Furthermore, network pharmacology analysis identified the top 10 hub genes, namely AKT1 (protein kinase B), CTNNB1 (catenin beta‐1), SRC (proto‐oncogene c‐Src), TNF (tumor necrosis factor), EGFR (epidermal growth factor receptor), HSP90AA1 (heat shock protein 90α), MAPK3 (mitogen‐activated protein kinase 3), STAT3 (signal transducer and activator of transcription 3), CASP3 (caspase protein), and ESR1 (estrogen receptor 1), which are responsible for hepatoprotective activity.

Conclusion

The findings demonstrate that AODE could be a novel hepatoprotective target in drug‐induced liver damage with a further single compound–based animal study.
Effect of macrophage‐to‐myofibroblast transition on silicosis
Authors: Geng Fei , Xu Jingrou , Ren Xichen , Zhao Ying , Cai Yuhao , Li Yaqian , Jin Fuyu , Li Tian , Gao Xuemin , Cai Wenchen , Xu Hong , Wei Zhongqiu , Mao Na , Sun Ying , Yang Fang
Published: July 2024

Background

The aim was to explore the effect of macrophage polarization and macrophage‐to‐myofibroblast transition (MMT) in silicosis.

Methods

Male Wistar rats were divided into a control group and a silicosis group developed using a HOPE MED 8050 dynamic automatic dusting system. Murine macrophage MH‐S cells were randomly divided into a control group and an SiO2 group. The pathological changes in lung tissue were observed using hematoxylin and eosin (HE) and Van Gieson (VG) staining. The distribution and location of macrophage marker (F4/80), M1 macrophage marker (iNOS), M2 macrophage marker (CD206), and myofibroblast marker (α‐smooth muscle actin [α‐SMA]) were detected using immunohistochemical and immunofluorescent staining. The expression changes in iNOS, Arg, α‐SMA, vimentin, and type I collagen (Col I) were measured using Western blot.

Results

The results of HE and VG staining showed obvious silicon nodule formation and the distribution of thick collagen fibers in the lung tissue of the silicosis group. Macrophage marker F4/80 increased gradually from 8 to 32 weeks after exposure to silica. Immunohistochemical and immunofluorescent staining results revealed that there were more iNOS‐positive cells and some CD206‐positive cells in the lung tissue of the silicosis group at 8 weeks. More CD206‐positive cells were found in the silicon nodules of the lung tissues in the silicosis group at 32 weeks. Western blot analysis showed that the expressions of Inducible nitric oxide synthase and Arg protein in the lung tissues of the silicosis group were upregulated compared with those of the control group. The results of immunofluorescence staining showed the co‐expression of F4/80, α‐SMA, and Col I, and CD206 and α‐SMA were co‐expressed in the lung tissue of the silicosis group. The extracted rat alveolar lavage fluid revealed F4/80+α‐SMA+, CD206+α‐SMA+, and F4/80+α‐SMA+Col I+ cells using immunofluorescence staining. Similar results were also found in MH‐S cells induced by SiO2.

Conclusions

The development of silicosis is accompanied by macrophage polarization and MMT.
Engineered Cellular Vesicles Displaying Glycosylated Nanobodies for Cancer Immunotherapy
Authors: Wu Jicheng , Lu Hailin , Xu Ximing , Rao Lang , Ge Yun
Published: July 2024

Immune checkpoint blockade targeting the CD47/SIRPα axis represents an alluring avenue for cancer immunotherapy. However, the compromised efficacy and safety concerns in vivo of conventional anti‐CD47 antibodies impede their wide clinical applications. Here we introduced a single type of high‐mannose glycans into the nanobody against CD47 (HM‐nCD47) and subsequently displayed HM‐nCD47 on cellular vesicles (CVs) for enhanced cancer immunotherapy. In this platform, the CVs significantly improved the circulation time of HM‐nCD47‐CVs, the nCD47 enabled the blockade of the CD47/SIRPα axis, and the HM enhanced recognition of mannose‐binding lectin, all synergistically activating the macrophage‐mediated antitumor immunity. In both subcutaneous and metastatic murine tumor models, the HM‐nCD47‐CVs possessed significantly extended half‐lives and increased accumulation at the tumor site, resulting in a remarkable macrophage‐dependent inhibition of tumor growth, a transcriptomic remodeling of the immune response, and an increase in survival time. By integrating the chemical biology toolbox with cell membrane nanotechnology, the HM‐nCD47‐CVs represent a new immunotherapeutic platform for cancer and other diseases.
Divergent Synthesis of 17‐nor‐Cephalotane Diterpenoids through Developed Ynol‐diene Cyclization
Authors: Sun Zezhong , Shu Xin , Ma Fuli , Li Ao , Li Yali , Jin Shuang , Wang Yunxia , Hu Xiangdong
Published: July 2024

On the basis of a novel ynol‐diene cyclization developed as a rapid access to tropone unit, the first divergent strategy to 17‐nor‐cephalotane diterpenoids has been successfully established. Combining with a bioinspired stereoselective dual hydrogenation, the divergent total synthesis of (+)‐3‐deoxyfortalpinoid F, (+)‐harringtonolide, (−)‐fortalpinoids M/N/P, and analog (−)‐20‐deoxocephinoid P have been achieved in 14–17 linear longest steps starting from commercially available materials.
Solvent‐Controlled Enantiodivergent Construction of P(V)‐Stereogenic Molecules via Palladium‐Catalyzed Annulation of Prochiral N‐Aryl Phosphonamides with Aromatic Iodides
Authors: Tian Qingyu , Ge Jin , Liu Yaopeng , Wu Xi , Li Zhenghao , Cheng Guolin
Published: July 2024

In this work, we describe an efficient and modular method for enantiodivergent accessing P(V)‐stereogenic molecules by utilizing the catalytic atroposelective Catellani‐type C−H arylation/desymmetric intramolecular N‐arylation cascade reaction. The enantioselectivity of this protocol was proved to be tuned by the polarity of the solvent, thus providing a wide range of both chiral P(V)‐stereogenic enantiomers in moderate to good yields with good to excellent enantiomeric excesses. Noteworthy is that the strategy developed herein represents an unprecedented example of solvent‐dictated inversion of the enantioselectivity of P(V)‐stereogenic compounds.
A novel Au nanoparticles/ionic liquids/N‐ and P‐co‐doped carbon nanotubes‐modified carbon cloth sensor for the sensitive detection of adrenaline
Authors: Cui Dan‐Dan , Liu Xue‐Ru , Meng Long‐Yue , Piao Ying‐ai , Jin Biao
Published: July 2024

Adrenaline (AD) is important in information transmission through the human central nervous system. Considering the significant biochemical functions of AD, the development of electrochemical sensors capable of detecting AD levels in living organisms has attracted considerable interest. In this study, AD was detected using electrochemical sensors developed based on Au nanoparticles/ionic liquids/N‐ and P‐co‐doped carbon nanotubes‐modified carbon cloth (AuNPs/ILs/N,P‐MWCNTs/CC) electrodes. AuNPs/ILs/N,P‐MWCNTs/CC composites were prepared on carbon cloth (CC) substrates using ionic liquids (ILs), N‐ and P‐co‐doped multi‐walled carbon nanotubes (N,P‐MWCNTs), and Au nanoparticles (AuNPs) as modified materials. The effects of pH and scanning speed were optimized and tested on the prepared composites. The results of cyclic voltammetry (CV) and differential pulse voltammetry (DPV) experiments showed that the modified ILs, N,P‐MWCNTs, and AuNPs effectively improved the oxidation performance of AD. In addition, the linear range obtained from the DPV scans of the AuNPs/ILs/N,P‐MWCNTs/CC composite material was 30–505 μmol/L, with a detection limit of 0.31 μmol/L. The fabricated sensors have good sensitivity (6.9 μA·mM−1·cm−2) for AD of 30–505 μM. Therefore, the electrochemical sensing method based on the AuNPs/ILs/N,P‐MWCNTs/CC composite material is a promising and reliable AD detection technology that also exhibits good selectivity in the presence of interfering substances such as folic acid and ibuprofen. In practical applications, this material can help realize real‐time AD detection to determine whether athletes use doping and other illegal drugs before competitions and to perform synchronous detection.
Heat exchange and damage of carbon black‐filled styrene‐butadiene rubber under uniaxial cyclic loading
Authors: Candau Nicolas , Fernandes João Paulo Cosas , Vives Eduard , Mudarra Lopez Miguel , Neira‐Viñas Marc , Maspoch Maria Lluisa
Published: July 2024

In this paper, we present an original experimental approach combining infrared thermography, analysis of voiding, and swelling tests to investigate damage mechanisms in carbon black (CB)‐filled styrene‐butadiene rubber (SBR). Heat exchange and voiding under uniaxial cyclic loading have been observed. A mechanical and electrical percolating filler network was identified by atomic force microscopy and electrical conductivity for the SBR with highest content of fillers (60 phr). SBR materials with a non percolating filler network show a reversible thermal energy dissipation during a series of cyclic loading, concomitant with reversible voiding mechanisms, through the successive formation and closing of voids. The SBR with the percolating network undergoes, during the series of cyclic loading, a high dissipation of energy under the form of heat, concomitantly with irreversible voiding mechanisms. Such mechanisms are shown to be due primarily to (i) the alteration of the filler network and/or filler/rubber interface and to a lower extent to (ii) the rubber matrix alteration (chains scission and/or crosslink breakage) as demonstrated by ex‐situ swelling.
A new semi‐fossorial thescelosaurine dinosaur from the Cenomanian‐age Mussentuchit Member of the Cedar Mountain Formation, Utah
Authors: Avrahami Haviv M. , Makovicky Peter J. , Tucker Ryan T. , Zanno Lindsay E.
Published: July 2024

Thescelosaurines are a group of early diverging, ornithischian dinosaurs notable for their conservative bauplans and mosaic of primitive features. Although abundant within the latest Cretaceous ecosystems of North America, their record is poor to absent in earlier assemblages, leaving a large gap in our understanding of their evolution, origins, and ecological roles. Here we report a new small bodied thescelosaurine—Fona herzogae gen. et sp. nov.—from the Mussentuchit Member of the Cedar Mountain Formation, Utah, USA. Fona herzogae is represented by multiple individuals, representing one of the most comprehensive skeletal assemblages of a small bodied, early diverging ornithischian described from North America to date. Phylogenetic analysis recovers Fona as the earliest member of Thescelosaurinae, minimally containing Oryctodromeus, and all three species of Thescelosaurus, revealing the clade was well‐established in North America by as early as the Cenomanian, and distinct from, yet continental cohabitants with, their sister clade, Orodrominae. To date, orodromines and thescelosaurines have not been found together within a single North American ecosystem, suggesting different habitat preferences or competitive exclusion. Osteological observations reveal extensive intraspecific variation across cranial and postcranial elements, and a number of anatomical similarities with Oryctodromeus, suggesting a shared semi‐fossorial lifestyle.
Molecular Docking and Molecular Dynamics Simulations of Synthesized Thiazole‐Isatin‐1,2,3‐triazole Hybrids as Promising Inhibitors for DNA Gyrase and 14α‐Sterol Demethylase
Authors: Kumar Vijay , Kumari Priya , Yadav Sandeep , Kumari Kamlesh , Jaglan Sundeep , Lal Kashmiri
Published: July 2024

In the present work, a new class of thiazole‐isatin‐1,2,3‐triazole hybrids (5a‐5p) and precursor alkyne hybrids (6a‐6d) has been reported with their in‐silico studies. After structural identifications using different spectroscopic technique such as FTIR, 1H and 13C NMR and HRMS, the synthesized hybrids were explored for their biological potential using molecular docking and molecular dynamics calculations. Molecular docking results revealed that compound 5j showed maximum binding energy i.e. ‐10.3 and ‐12.6 kcal/mol against antibacterial and antifungal enzymes; 1KZN (E. coli) and 5TZ1 (C. albicans), respectively.Top of FormBottom of Form Molecular dynamics simulations for the best molecule (100 ns) followed by PBSA calculations  suggested a stable complex of 5j with 5TZ1 with binding energy of ‐118.760 kJ/mol as compared to 1KZN (‐94.593 kJ/mol). The mean RMSD values for the 1KZN with 5j complex remained approximately 0.175 nm throughout all the time span of 100 ns in the production stages and is in the acceptable range.  Whereas, 5TZ1 with 5j complex, RMSD values exhibited variability within the range of 0.15 to 0.25 nm.
A detached helix of pacemaker pacing lead
Authors: Zheng Jing , Jin Qizhi , Cheng Keyun
Published: July 2024

Key Clinical Message

Permanent pacemaker implantation is the main treatment of symptomatic bradyarrhythmia, which has been widely used. Lead implantation is a critical step. When the lead malfunctions and needs to be replaced, extraction or abandonment of the primary lead (in whole or in part) should be determined according to the situation.
Heterocyclic Hemipiperazines: Multistimuli‐Responsive Switches and Sensors for Zinc or Cadmium Ions
Authors: Schäfer Valentin , Pianowski Zbigniew L.
Published: July 2024

Advance in the design of molecular photoswitches ‐ adapters that convert light into changes at molecular level ‐ opens up exciting possibilities in preparing smart polymers, drugs photoactivated inside humans, or light‐fueled nanomachines that might in the future operate in our bloodstream. Hemipiperazines are recently reported biocompatible molecular photoswitches based on cyclic dipeptides. Here we report a multistimuli‐responsive hemipiperazine‐based switch that reacts on light, solvents, acidity, or metal ions. Its photoequilibration is controlled by the intramolecular hydrogen bonding pattern. The compound can be used as a mid‐nanomolar photoswitchable fluorescent sensor for zinc and cadmium ions, applicable to monitor environmental pollution in real time.
Radical‐Chain Hydrosilylation of Alkenes Enabled by Triplet Energy Transfer
Authors: Guo Shixun , Wang Wei , Zhang Yongqiang
Published: July 2024

Development of mild, robust and metal‐free catalytic approach for the hydrosilylation of alkenes is critical to the advancement of modern organosilicon chemistry given their powerful capacity in the construction of various C−Si bonds. Herein, we wish to disclose a visible light‐triggered organophotocatalytic strategy, which proceeds via a triplet energy transfer (EnT)‐enabled radical chain pathway. Notably, this redox‐neutral protocol is capable of accommodating a broad spectrum of electron‐deficient and ‐rich alkenes with excellent functional group compatibility. Electron‐deficient alkenes are more reactive and the reaction could be finished within a couple of minutes even in PBS solution with extremely low concentration, which suggests its click‐like potential in organic synthesis. The preparative power of the transformations has been further highlighted in a number of complex settings, including the late‐stage functionalization and scale‐up experiments. Furthermore, although only highly reactive (TMS)3SiH is suitable hydrosilane substrate, our studies revealed the great reactivity and versatility of (TMS)3Si− group in diverse C−Si and Si−Si bond cleavage‐based transformations, enabling the rapid introduction of diverse functional groups and the facile construction of valuable quaternary silicon architectures.
Multidimensional Scenario Calculations Using Cloud‐Based Co‐Simulation
Authors: Wack Thorsten , Schröder Andreas
Published: July 2024

As part of the joint research project Carbon2Chem®, mathematical models are used to simulate operating scenarios of cross‐industry networks, in particular chemical plants in industrial environments with high CO2 emissions. In this context, a cloud‐based distributed co‐simulation is used to enable the parallelized simulation of a large number of different variants. This enables optimal design of the plant networks and the efficient determination of optimal operating conditions. The architecture of this approach is described, and its performance is examined and evaluated.
Computational comparison study of virtual compression and shear test for estimation of apparent elastic moduli under various boundary conditions
Authors: Kim Jisun , Kim Jung Jin
Published: July 2024

Virtual compression tests based on finite element analysis are representative noninvasive methods to evaluate bone strength. However, owing to the characteristic porous structure of bones, the material obtained from micro‐computed tomography images in the finite‐element model is not uniformly distributed. These characteristics cause differences in the apparent elastic moduli depending on the boundary conditions and affect the accuracy of bone‐strength evaluation. Therefore, this study aimed to evaluate and compare the apparent elastic moduli under various, virtual‐compression and shear‐test boundary conditions. Four, nonuniform models were constructed with increasing model complexity. For representative boundary conditions, two, different, testing directions, and constrained surfaces were applied. As a result, the apparent elastic moduli of the nonuniform model varied up to 55.2% based on where the constrained surface was located in the single‐end‐cemented condition. Additionally, when connectivity in the test direction was lost, the accuracy of the apparent elastic moduli was low. A graphical comparison showed that the equivalent‐stress distribution was more advantageous for analyzing load transferability and physical behavior than the strain‐energy distribution. These results clearly show that the prediction accuracy of the apparent elastic moduli can be guaranteed if the boundary condition on the constraint and loading surfaces of the nonuniform model are applied symmetrically and the connectivity of the elements in the testing direction is well maintained. This study will aid in precision improvement of bone‐strength‐indicator determination for osteoporosis prevention.
Efficient Hydrodeoxygenation of Lignin‐Derived Phenolic Compounds over Bifunctional Catalyst Comprising H4PMo11VO40 Coupled with Ni/C
Authors: Yin Tao , Luo Yang , Singh Chauhan Arvind , Shu Riyang , Tian Zhipeng , Wang Chao , Chen Ying , Kumar Gupta Navneet
Published: July 2024

In the catalytic transformation of bio‐oil into liquid fuels having alkanes via hydrodeoxygenation (HDO), the acid and metal sites in the catalyst are pivotal for promoting the HDO of lignin‐derived phenolic compounds. This study introduces a novel bifunctional catalyst comprising phosphomolybdenum‐vanadium heteropolyacids (H4PMo11VO40) coupled with Ni/C. The HDO reaction of the model compound guaiacol was carried out under reaction conditions of 230 °C, revealing the superior performance of H4PMo11VO40 with Ni/C catalysts compared to the conventional acids, even at low dosage. The Keggin structure of H4PMo11VO40 provided a solid catalyst with strong acidic and redox properties, alongside advantages such as ease of synthesis, cost‐effectiveness, and tunable acid and redox properties at the molecular level. Characterization of Ni/C and the prepared acid demonstrated favorable pore structure with a mesopore volume of 0.281 cm3/g and an average pore size of 3.404 nm, facilitating uniform distribution and catalytic activity of Ni‐metal. Incorporating acid enhances the acidic sites, fostering synergistic interactions between metal and acidic sites within the catalyst, thereby significantly enhancing HDO performance. Guaiacol conversion at 230 °C reached 100 %, with a cyclohexane selectivity of 89.3 %. This study offers a promising avenue for the conversion and upgrading of lignin‐derived phenolic compounds.
Towards a motivating language acquisition curriculum
Authors: Printer Liam
Published: July 2024

Motivation is repeatedly found to be a determining factor for achievement in language acquisition at school. Decades of Self‐determination theory (SDT) research has shown that students exhibit higher levels of engagement and positive learning behaviours when their basic psychological needs of competence, autonomy and relatedness are satisfied, resulting in intrinsic motivation. This paper explores and juxtaposes the motivational potential of the International Baccalaureate curriculum against the revised GCSE modern foreign language (MFL) curriculum through an SDT lens. A curriculum that is autonomy‐supportive rather than autonomy‐suppressive allows more opportunities for both students and teachers psychological needs for motivation to be met.
Identification of hyaluronic acid in seized samples by Hypercarb chromatography–high resolution mass spectrometry
Authors: Steel Rohan
Published: July 2024

Hyaluronic acid (HA) has been commonly used to treat osteoarthritis and joint injuries in horses and dogs since the 1970s. HA is a polysaccharide made up of alternating N‐acetyl‐d‐glucosamine and d‐glucuronic acid residues, with polymeric molecules achieving molecular weights as high as 20 MDa. High molecular weight HA forms a viscous hydrogel when dissolved in water, making HA solutions distinct from most other pharmaceutical preparations. Clear viscous solutions are often encountered during stable and kennel inspections, but in the absence of an analytical method, it is not possible to identify if these substances contain HA or other unknown compounds. This paper presents a simple method for the identification of HA in seized materials based on chemical hydrolysis followed by Hypercarb chromatography and MS/MS analysis.