bluuebunny/crossref_metadata_2025 huggingface dataset:
Vicious Cycle‐Breaking Lipid Nanoparticles Remodeling Multicellular Crosstalk to Reverse Liver Fibrosis
Authors: Zhang Ling‐Feng , Deng Wen‐Qi , Huang Qing‐Wen , Zhang Jiao‐Jiao , Wang Yi , Zhou Tian‐Jiao , Xing Lei , Jiang Hu‐Lin
Published: January 2024

During liver fibrogenesis, the reciprocal crosstalk among capillarized liver sinusoidal endothelial cells (LSECs), activated hepatic stellate cells (HSCs), and dysfunctional hepatocytes constructs a self‐amplifying vicious cycle, greatly exacerbating the disease condition and weakening therapeutic effect. Limited by the malignant cellular interactions, the previous single‐cell centric treatment approaches show unsatisfactory efficacy and fail to meet clinical demand. Herein, a vicious cycle‐breaking strategy is proposed to target and repair pathological cells separately to terminate the malignant progression of liver fibrosis. Chondroitin sulfate‐modified and vismodegib‐loaded nanoparticles (CS‐NPs/VDG) are designed to efficiently normalize the fenestrae phenotype of LSECs and restore HSCs to quiescent state by inhibiting Hedgehog signaling pathway. In addition, glycyrrhetinic acid‐modified and silybin‐loaded nanoparticles (GA‐NPs/SIB) are prepared to restore hepatocytes function by relieving oxidative stress. The results show successful interruption of vicious cycle as well as distinct fibrosis resolution in two animal models through multiregulation of the pathological cells. This work not only highlights the significance of modulating cellular crosstalk but also provides a promising avenue for developing antifibrotic regimens.
Modifying Surface Termination by Bidentate Chelating Strategy Enables 13.77% Efficient Kesterite Solar Cells
Authors: Cao Lei , Wang Lijing , Zhou Zhengji , Zhou Tianxiang , Li Rui , Zhang Hao , Wang Zhiteng , Wu Sixin , Najar Adel , Tian Qingwen , (Frank) Liu Shengzhong
Published: January 2024

Surfaces display discontinuities in the kesterite‐based polycrystalline films can produce large defect densities, including strained and dangling bonds. These physical defects tend to introduce electronic defects and surface states, which can greatly promote nonradiative recombination of electron–hole pairs and damage device performance. Here, an effective chelation strategy is reported to suppress these harmful physical defects related to unterminated Cu, Zn, and Sn sites by modifying the surface of Cu2ZnSn(S,Se)4 (CZTSSe) films with sodium diethyldithiocarbamate (NaDDTC). The conjoint theoretical calculations and experimental results reveal that the NaDDTC molecules can be coordinate to surface metal sites of CZTSSe films via robust bidentate chelating interactions, effectively reducing surface undercoordinated defects and passivating the electron trap states. Consequently, the solar cell efficiency of the NaDDTC‐treated device is increased to as high as 13.77% under 100 mW cm−2 illumination, with significant improvement in fill factor and open‐circuit voltage. This surface chelation strategy provides strong surface termination and defect passivation for further development and application of kesterite‐based photovoltaics.
Native Capillary Electrophoresis–Mass Spectrometry of Near 1 MDa Non‐Covalent GroEL/GroES/Substrate Protein Complexes
Authors: Marie Anne‐Lise , Georgescauld Florian , Johnson Kendall R. , Ray Somak , Engen John R. , Ivanov Alexander R.
Published: January 2024

Protein complexes are essential for proteins' folding and biological function. Currently, native analysis of large multimeric protein complexes remains challenging. Structural biology techniques are time‐consuming and often cannot monitor the proteins' dynamics in solution. Here, a capillary electrophoresis‐mass spectrometry (CE–MS) method is reported to characterize, under near‐physiological conditions, the conformational rearrangements of ∽1 MDa GroEL upon complexation with binding partners involved in a protein folding cycle. The developed CE–MS method is fast (30 min per run), highly sensitive (low‐amol level), and requires ∽10 000‐fold fewer samples compared to biochemical/biophysical techniques. The method successfully separates GroEL14 (∽800 kDa), GroEL7 (∽400 kDa), GroES7 (∽73 kDa), and NanA4 (∽130 kDa) oligomers. The non‐covalent binding of natural substrate proteins with GroEL14 can be detected and quantified. The technique allows monitoring of GroEL14 conformational changes upon complexation with (ATPγS)4–14 and GroES7 (∽876 kDa). Native CE‐pseudo‐MS3 analyses of wild‐type (WT) GroEL and two GroEL mutants result in up to 60% sequence coverage and highlight subtle structural differences between WT and mutated GroEL. The presented results demonstrate the superior CE–MS performance for multimeric complexes' characterization versus direct infusion ESI–MS. This study shows the CE–MS potential to provide information on binding stoichiometry and kinetics for various protein complexes.
Intersection of Immunity, Metabolism, and Muscle Regeneration in an Autoimmune‐Prone MRL Mouse Model
Authors: Ngo Tran B. , Josyula Aditya , DeStefano Sabrina , Fertil Daphna , Faust Mondreakest , Lokwani Ravi , Sadtler Kaitlyn
Published: January 2024

Due to the limited capacity of mammals to regenerate complex tissues, researchers have worked to understand the mechanisms of tissue regeneration in organisms that maintain that capacity. One example is the MRL/MpJ mouse strain with unique regenerative capacity in ear pinnae that is absent from other strains, such as the common C57BL/6 strain. The MRL/MpJ mouse has also been associated with an autoimmune phenotype even in the absence of the mutant Fas gene described in its parent strain MRL/lpr. Due to these findings, the differences between the responses of MRL/MpJ versus C57BL/6 strain are evaluated in volumetric muscle injury and subsequent material implantation. One salient feature of the MRL/MpJ response to injury is robust adipogenesis within the muscle. This is associated with a decrease in M2‐like polarization in response to biologically derived extracellular matrix scaffolds. In pro‐fibrotic materials, such as polyethylene, there are fewer foreign body giant cells in the MRL/MpJ mice. As there are reports of both positive and negative influences of adipose tissue and adipogenesis on wound healing, this model can provide an important lens to investigate the interplay between stem cells, adipose tissue, and immune responses in trauma and material implantation.
Controllable Assembly of Highly Oxidized Cobalt on Graphdiyne Surface for Efficient Conversion of Nitrogen into Nitric Acid
Authors: Zheng Xuchen , Wu Han , Gao Yang , Chen Siao , Xue Yurui , Li Yuliang
Published: January 2024

The manufacture of nitric acid (HNO3) consumes large amounts of energy and causes serious environmental pollution. Electrochemical synthesis is regarded as a key way to eliminate carbon emissions from the chemicals industry. The selective electrosynthesis of HNO3 from nitrogen was achieved by controllable assembly of cobalt metal on graphdiyne surface using a powerful tool of electrochemistry at ambient conditions. As an advanced material, graphdiyne (GDY) has a large conjugated structure on its surface and is rich in sp‐C triple bond skeleton, which can achieve strong interaction with metal atoms, resulting in incomplete charge transfer between graphdiyne and cobalt atoms. The experimental and theoretical calculation results show that the highly oxidized cobalt on graphdiyne (HOCo/GDY) can selectively and efficiently activate and convert the nitrogen into the key intermediate *NO, which promotes the efficient overall conversion performance of nitrogen to nitric acid. Thus, the highest nitric acid yield (192.0 μg h−1 mg−1) and Faradaic efficiency (21.5 %) were achieved at low potentials.
Metallo‐Supramolecular Helical Fibres from Chiral Phenylacetylene Monomers: Cation Induced Self‐Assembly
Authors: Rey‐Tarrío Francisco , Simón‐Fuente Silvia , Cuerva Juan M. , Miguel Delia , Ribagorda Maria , Quiñoá Emilio , Freire Félix
Published: January 2024

Chiral metallo‐supramolecular fibres can be easily obtained by mixing a chloroform solution of a phenylacetylene monomer (PA) that bears a chiral sulfoxide group as pendant, with different equivalents of a methanolic solution of AgClO4. Thus, while the PA is found molecularly dissolved in chloroform, the addition of Ag+ ions induce its aggregation through the formation of an axially chiral metallo‐supramolecular aggregate with high thermal stable properties. In this case, the ability of the metal ion to coordinate the PA triple bond, combined with the argentophilicity of the metal ion and the planarity of the phenylacetylene drives to the formation of a helical coordination polymer, whose P or M axial chirality is determined by the chirality of the sulfoxide used as substituent of the PA. Depending on the PA/Ag+ (mol/mol) ratio, it is possible to tune the morphology of the metallo‐supramolecular aggregate from chiral fibers to chiral gel.
L‐Glycosidase‐Cleavable Natural Glycans Facilitate the Chemical Synthesis of Correctly Folded Disulfide‐Bonded D‐Proteins
Authors: Shi Weiwei , Wang Tongyue , Yang Ziyi , Ren Yuxiang , Han Dongyang , Zheng Yupeng , Deng Xiangyu , Tang Shan , Zheng Ji‐Shen
Published: January 2024

D‐peptide ligands can be screened for therapeutic potency and enzymatic stability using synthetic mirror‐image proteins (D‐proteins), but efficient acquisition of these D‐proteins can be hampered by the need to accomplish their in vitro folding, which often requires the formation of correctly linked disulfide bonds. Here, we report the finding that temporary installation of natural O‐linked‐β‐N‐acetyl‐D‐glucosamine (O‐GlcNAc) groups onto selected D‐serine or D‐threonine residues of the synthetic disulfide‐bonded D‐proteins can facilitate their folding in vitro, and that the natural glycosyl groups can be completely removed from the folded D‐proteins to afford the desired chirally inverted D‐protein targets using naturally occurring O‐GlcNAcase. This approach enabled the efficient chemical syntheses of several important but difficult‐to‐fold D‐proteins incorporating disulfide bonds including the mirror‐image tumor necrosis factor alpha (D‐TNFα) homotrimer and the mirror‐image receptor‐binding domain of the Omicron spike protein (D‐RBD). Our work establishes the use of O‐GlcNAc to facilitate D‐protein synthesis and folding and proves that D‐proteins bearing O‐GlcNAc can be good substrates for naturally occurring O‐GlcNAcase.
Photo‐Controlled Calcium Overload from Endogenous Sources for Tumor Therapy
Authors: Hu Jing‐Jing , Yuan Lizhen , Zhang Yunfan , Kuang Jing , Song Wen , Lou Xiaoding , Xia Fan , Yoon Juyoung
Published: January 2024

Designing reactive calcium‐based nanogenerators to produce excess calcium ions (Ca2+) in tumor cells is an attractive tumor treatment method. However, nanogenerators that introduce exogenous Ca2+ are either overactive incapable of on‐demand release, or excessively inert incapable of an overload of calcium rapidly. Herein, inspired by inherently diverse Ca2+‐regulating channels, a photo‐controlled Ca2+ nanomodulator that fully utilizes endogenous Ca2+ from dual sources was designed to achieve Ca2+ overload in tumor cells. Specifically, mesoporous silica nanoparticles were used to co‐load bifunctional indocyanine green as a photodynamic/photothermal agent and a thermal‐sensitive nitric oxide (NO) donor (BNN‐6). Thereafter, they were coated with hyaluronic acid, which served as a tumor cell‐targeting unit and a gatekeeper. Under near‐infrared light irradiation, the Ca2+ nanomodulator can generate reactive oxygen species that stimulate the transient receptor potential ankyrin subtype 1 channel to realize Ca2+ influx from extracellular environments. Simultaneously, the converted heat can induce BNN‐6 decomposition to generate NO, which would open the ryanodine receptor channel in the endoplasmic reticulum and allow stored Ca2+ to leak. Both in vitro and in vivo experiments demonstrated that the combination of photo‐controlled Ca2+ influx and release could enable Ca2+ overload in the cytoplasm and efficiently inhibit tumor growth.
Impact of single and mixed cultures of yeasts and lactic acid bacteria in coffee fermentation and cup quality
Authors: Estela‐Escalante Waldir D. , Rodriguez‐Portilla Liz M. I. , Pinillos‐Miñano Ricardo M. , Rojas‐Ocupa Elton J. , Lozada‐Castillo Karina L. , Hatta‐Sakoda Beatriz A. , Pérez Americo Guevara
Published: January 2024

Saccharomyces cerevisiae LBTF 21.3, Pichia manshurica LBTF 21.1, and Leuconostoc lactis LBTF 21.1 were used as single and mixed cultures in coffee fermentations. Fermentations carried out in glass jars with P. manshurica LBTF 21.1/Leuc. lactis LBTF 21.1 showed higher fermentation rates than S. cerevisiae LBTF 21.3/P. manshurica LBTF 21.1 or S. cerevisiae LBTF 21.3/Leuc. lactis LBTF 21.1. The highest cup quality was reached with P. manshurica LBTF 21.1/Leuc. lactis LBTF 21.1 (83.0 points). Full factorial design (22) carried out with P. manshurica LBTF 21.1 revealed that the higher proportion of water added before the fermentation resulted in higher production of acetic acid. A contrary effect of this variable was observed on the production of lactic acid with Leuc. lactis LBTF 21.1. Fermentations conducted in bioreactor evidenced the production of acetaldehyde by P. manshurica LBTF 21.1/Leuc. lactis LBTF 21.1, P. manshurica LBTF 21.1, and Leuc. lactis LBTF 21.1. Additionally, the highest cup quality was reached in fermentations with P. manshurica LBTF 21.1 (82.5 points) followed by Leuc. lactis LBTF 21.1 (81.5 points) and P. manshurica LBTF 21.1/Leuc. lactis LBTF 21.1 (81.0 points). Fermentations of coffee with single and mixed cultures are interesting strategies for the improvement of the sensory quality.
Good new(t)s: Rapid recolonization of a restored fish‐invaded habitat by two newt species in southern Italy
Authors: Chiacchio Michele , Paudice Giuseppe , Senese Andrea , Russo Valerio Giovanni
Published: January 2024

Habitat modification and invasive species are considered some of the most impelling causes of the ongoing sixth mass extinction, especially in freshwater ecosystems. Artificial water troughs are, in this regard, particularly vulnerable environments, while being pivotal breeding habitats for many amphibian species. However, despite their well‐known importance and their conservation concern, detailed information on the resilience of such ecosystems is lacking.

This note describes the events following the introduction of invasive fish species into a water trough in southern Italy and reconstructs the recolonization times of two newt species (Lissotriton italicus, Triturus carnifex) after disappearance of the fish a few months later.

As expected, both newt species were no longer observed in the water as soon as the fish were introduced in the trough. However, in contrast to previous reports, they recolonized it within 2 months of the last observation of fish and, in the case of L. italicus, bred shortly after.

Although the short permanence of fish in the trough may have facilitated the recolonization process, this event represents the fastest recolonization by newts of a restored habitat ever reported in the wild and sheds further insights on the resilience of amphibian species.
In vitro protein protection of protein meals using Bioprotect and tannin extract from red grape marc
Authors: Tunkala Bereket Zeleke , DiGiacomo Kristy , Alvarez Hess Pablo S. , Dunshea Frank R. , Leury Brian J.
Published: January 2024

Protecting crude protein in the rumen may reduce extensive protein degradation and ammonia emission and increase available bypass protein in ruminants. This experiment was conducted to determine the effect of two Bioprotect (15 and 30 mL/kg dry matter (DM)) and two tannin extract (TE) (20 and 40 g/kg DM) inclusion rates on protein protection and in vitro fermentation characteristics of canola and soybean meals incubated for 24 h using an ANKOM in vitro gas production system. The treated canola and soybean meals produced lower soluble protein (fraction ‘a’) and larger slowly degradable protein (fraction ‘b’) than its untreated counterparts, p < 0.01. However, the 20 g/kg DM TE inclusion showed lowest effect on the amount of protein fractions ‘a’ and ‘b’ in both meals compared to their other treated counterparts. The increasing concentration of additives reduced the total volatile fatty acids (VFA), p < 0.001. The effects of additives differed between the treatments as 15 mL/kg DM Bioprotect and 20 g/kg DM TE did not affect the acetic to propionic acid ratio (A:P) and the time before gas production began. The increase in fraction ‘b’ and reduction in protein fraction ‘a’ confirm successful protein protection in this experiment. However, the extensive reduction in ammonia‐N and in vitro degradable protein after using 30 mL/kg DM Bioprotect suggests possible toxicity to the microbes responsible for protein digestion in higher doses. Therefore, 15 mL/kg DM Bioprotect and 40 g/kg DM TE could be promising protein protection doses for in vitro experiments.
Light vector mesons photoproduction and nuclear shadowing
Authors: Trebien Haimon
Published: January 2024

In this work, we study the photoproduction of mesons considering the proton and the nucleus as the target. Utilizing the dipole picture and the wave functions obtained via AdS/QCD, we were able to describe the HERA data and extend the formalism to the nuclear case considering the Glauber–Gribov model. The preliminary results obtained in the nuclear regime are compared to the recent LHC data and suggest the presence of a nuclear effect called shadowing.
Correlation between essential and toxic elements in maternal blood during early pregnancy and atrial septal defects/ventricular septal defects/patent ductus arteriosus in offspring
Authors: Gu Jianli , Jin Zhen , Wu Guiqing , Dang Shaonong , Yao Feng , Zheng Zihan , Ren Lingxuan , Yang Jianjun , Chen Danli , Zhang Li , Lin Rong
Published: January 2024

Background

Congenital heart defects (CHDs) are the most common congenital malformation in the world. Recent studies have found that essential and toxic trace element levels may play a crucial role in the risk of neonatal malformation. However, the relationships between element levels in early pregnancy and CHD risk among humans remain unclear. This study investigates the association between maternal essential element (copper [Cu], zinc [Zn], calcium [Ca], manganese [Mg] and iron [Fe]) and toxic element (lead [Pb] and cadmium [Cd]) levels during early pregnancy and CHDs.

Methods

A hospital‐based case–control study was conducted, including 181 cases and 218 controls. Eligible participants underwent antenatal examination during gestational weeks 11–14 and trace element levels were detected by the atomic absorption method. Multi‐variable logistic regression was used to examine the associations between the level of maternal trace elements and CHD risks.

Results

Higher levels of Ca in early pregnancy were associated with lower risk of ASD/VSD risks. Moreover, higher Fe, Pb, and Cd levels in the first trimester were associated with higher risks of all CHD and the subtypes risks, and the tests for trend were significant (all p < .05). The restricted cubic spline analysis showed that there was a nonlinear inverted u‐shaped dose–response relationship between levels of Zn, Pb, and Cd in the first trimester and risk of CHDs (non‐linearity test p < .05).

Conclusions

A moderate increase in Zn and Ca levels and a decrease in Pb and Cd levels during early pregnancy are needed to reduce the incidence of CHDs in the Chinese population.
Learning from failure: A context‐informed perspective on RCTs
Authors: Coldwell Mike , Moore Nick
Published: January 2024

Discussions of randomised controlled trials (RCTs) in education that do not show an impact regularly focus on the intervention and how it failed to impact on expected measures, with typologies identifying persistent critical points of failure. This paper uses one such RCT—the Integrating English programme—to exemplify the application of a new model to explain failure in RCTs. To do so, the paper develops a set of categories of context drawing on the wider social evaluation field: backdrop, design, operation and interpretation. Thus, the paper exposes critical weak points in the commission and interpretation, as well as the implementation, of an RCT. Our aim is to work towards more robust evaluations by demonstrating that it is not simply the programme design, implementation and evaluation that can contribute to a lack of impact; there can be more fundamental system issues at play.
Lemon extract reduces the hepatic oxidative stress and persulfidation levels by upregulating the Nrf2 and Trx1 expression in old rats
Authors: Miler Marko , Živanović Jasmina , Ajdžanović Vladimir , Milenkovic Dragan , Cesar Thais , Filipović Miloš R. , Milošević Verica
Published: January 2024

Citrus flavanones are recognized as promising bioactives within the concept of healthy aging. Thus, the present study investigated the effects of a nutritionally relevant dose of lemon extract (LE) on liver redox regulation and persulfidation levels in 24‐month‐old Wistar rats. LE (40 mg/kg b.m.) was administered orally once daily for 4 weeks. Control groups received either vehicle (sunflower oil) or remained intact. The applied methodology considered qPCR, Western blot, protein persulfidation levels evaluation, histochemistry in line with immunofluorescence, liver biochemical assays (glutathione, total ‐SH groups and malonaldehyde; MDA), liver enzymes in serum and in silico analysis to explore the potential interaction/binding between the proteins studied in the paper. Our results showed that LE increased glutathione peroxidase (GPx), reductase (GR), glutamate–cysteine ligase catalytic and modifier subunit, respectively, as well as Nrf2 gene expressions, but decreased the expression of superoxide dismutase 2 (SOD2). Upon LE application, protein expression showed upregulation of NRF2, SOD2, GPx, GR, and thioredoxin 1 (Trx1). LE significantly decreased the protein persulfidation levels and concentration of MDA, a marker of oxidative damage in the cell. Histological analysis showed a normal liver histoarchitecture without pathological changes, aligning with the normal serum level of hepatic enzymes. Obtained results showed that LE, by modulating hepatic redox regulators Nrf2 and Trx1, diminishes oxidative stress and alters the persulfidation levels, suggesting a considerable beneficial antioxidant potential of lemon flavanones in the old‐aged liver.
Novel Benzotriazole‐β‐lactam Derivatives as Antimalarial Agents: Design, Synthesis, Biological Evaluation and Molecular Docking Studies
Authors: Aye Malihe , Jarrahpour Aliasghar , Haghighijoo Zahra , Heiran Roghayeh , Pournejati Roya , Karbalaei‐Heidari Hamid Reza , Sinou Veronique , Brunel Jean Michel , Akkurt Mehmet , Özdemir Namık , Turos Edward
Published: January 2024

Many people around the world suffer from malaria, especially in tropical or subtropical regions. While malaria medications have shown success in treating malaria, there is still a problem with resistance to these drugs. Herein, we designed and synthesized some structurally novel benzotriazole‐β‐lactams using 2‐(1H‐benzo[d][1,2,3]triazol‐1‐yl)acetic acid as a key intermediate. To synthesize the target molecules, the ketene‐imine cycloaddition reaction was employed. First, The reaction of 1H‐benzo[d][1,2,3]triazole with 2‐bromoacetic acid in aqueous sodium hydroxide yielded 2‐(1H‐benzo[d][1,2,3]triazol‐1‐yl)acetic acid. Then, the treatment of 2‐(1H‐benzo[d][1,2,3]triazol‐1‐yl)acetic acid with tosyl chloride, triethyl amine, and Schiff base provided new β‐lactams in good to moderate yields.The formation of all cycloadducts was confirmed by elemental analysis, FT‐IR, NMR and mass spectral data. Moreover, X‐ray crystallography was used to determine the relative stereochemistry of 4a compound. The in vitro antimalarial activity test was conducted for each compound against P. falciparum K1. The IC50 values ranged from 5.56 to 25.65 μM. A cytotoxicity profile of the compounds at 200 μM final concentration revealed suitable selectivity of the compounds for malaria treatment. Furthermore, the docking study was carried out for each compound into the P. falciparum dihydrofolate reductase enzyme (PfDHFR) binding site to analyze their possible binding orientation in the active site.
Cyanide poisoning after bitter almond ingestion: “A rare case report”
Authors: Arabizadeh Neda , Mahmoudi Masoud , Gandomani Laaya Mokhtar , Eizadi‐Mood Nastaran
Published: January 2024

Key Clinical Message

We present a case of a 36‐year‐old woman with a history of three suicide attempts who had ingested approximately 40 bitter almonds in a suicidal act, leading to her admission to the emergency department of a regional hospital due to complaints of vomiting. Upon arrival, she exhibited confusion, and her vital signs were recorded as follows: pulse rate = 117 beats/min, blood pressure = 160/85 mmHg, oxygen saturation = 95%, respiratory rate = 16, temperature = 37°C. The patient venous blood gas analysis manifested severe metabolic acidosis (pH = 6.92, pO2 = 43 mmHg, HCO3 = 8.6 mmol/L, pCO2 = 42.7 mmHg, base excess = −25.9 mmol/L). Four hours later, she became unconscious and she was intubated. Gastric lavage and a single dose of 60 g of activated charcoal and sodium bicarbonate were administered. In the referral hospital, sodium nitrite was given due to the severity of the poisoning, and norepinephrine infusion was initiated to manage hypotension. Within a day, the patient regained consciousness, underwent extubation, and after 72 h was discharged and subsequently transferred to psychiatric care for further treatment. This case underscores the critical, life‐threatening implications of cyanide toxicity following the ingestion of bitter almonds, highlighting the efficacy of supportive measures such as gastric lavage, activated charcoal, and sodium bicarbonate. Furthermore, it emphasizes the successful application of sodium nitrite monotherapy in managing this condition.
Enhanced luminescence of a silica‐nitride phosphor; La3Si6N11:Ce3+by using Cr3+‐activated TiO2 nanoparticles
Authors: Aydin Ilkyaz , Ertekin Kadriye , Azem Funda Ak , Delice Tulay Koc , Birlik Isil
Published: January 2024

Ce3+‐activated silica nitride phosphors (lanthanum silicate‐nitride [LSN]) are promising thermostable conversion components for white‐light‐emitting diodes, screen technologies, and other optoelectronic applications. Cr3+‐activated TiO2, on the other hand, is a strongly absorbing material depending on its size and optical microenvironment. In this work, we gathered Cr3+‐doped TiO2 and La3Si6N11:Ce3+ in an optically transparent polymethylmethacrylate matrix. Photoluminescence of the binary blends of La3Si6N11:Ce3+/TiO2 and La3Si6N11:Ce3+/TiO2:Cr3+ has been investigated under two different excitation energies by steady‐state and lifetime‐based measurements, respectively. When the microscale La3Si6N11:Ce3+ phosphor and nanoscale TiO2:Cr3+ particles were gathered at a critical concentration, the resulting composite exhibited 3.14‐fold enhancement in the emission signal intensity with respect to the additive‐free phosphor. Upon excitation, the La3Si6N11:Ce3+–TiO2:Cr3+ blend exhibited different excited‐state lifetimes for the nano‐ and microsecond time‐scales compared to the LSN. The microsecond time‐scale measurements performed under 378 nm excitation supported the existence of a potential energy transfer from the TiO2:Cr3+ to the La3Si6N11:Ce3+.
Enhancing the Features of DNA Mimic Foldamers for Structural Investigations
Authors: Corvaglia Valentina , Wu Jiaojiao , Deepak Deepak , Loos Manuel , Huc Ivan
Published: January 2024

DNA mimic foldamers based on aromatic oligoamide helices bearing anionic phosphonate side chains have been shown to bind to DNA‐binding proteins sometimes orders of magnitude better than DNA itself. Here, we introduce new features in the DNA mimic foldamers to facilitate structural investigations of their interactions with proteins. Thirteen new foldamer sequences have been synthesized and characterized using NMR, circular dichroism, molecular modeling, and X‐ray crystallography. The results show that foldamer helix handedness can be quantitatively biased by means of a single stereogenic center, that the foldamer structure can be made C2‐symmetrical as in palindromic B‐DNA sequences, and that associations between foldamer helices can be promoted utilizing dedicated C‐terminal residues that act as sticky ends in B‐DNA structures.
Comparability of Elezanumab Safety, Tolerability, and Pharmacokinetics in Healthy Japanese, Chinese, and White Participants
Authors: Kalluri Hari V. , Rosebraugh Matthew R. , Boehm Nils , Locke Charles , Ziemann Adam , Xiong Hao
Published: January 2024

Elezanumab is a fully human monoclonal antibody, which is directed against repulsive guidance molecule A. The safety, tolerability, pharmacokinetics (PK), and immunogenicity of elezanumab were assessed in 2 Phase 1 clinical studies. The objective of this study was to assess the PK, safety, tolerability, and immunogenicity following intravenous infusion of elezanumab in healthy adult Japanese, Han Chinese, and Caucasian participants as well as Western participants from the single‐ascending‐dose study. Elezanumab exposures were approximately 20% higher in Japanese and Han Chinese participants compared to White participants without controlling for body weight. After statistically controlling for body weight by including it as a covariate, the PK of elezanumab in White participants were comparable to those in Japanese and Han Chinese participants. The clinical implications of these exposure differences are yet to be determined. All adverse events were assessed by the investigator as having no reasonable possibility of being related to the study drugs and were mild in severity. No positive immunogenicity effect was observed that impacted elezanumab exposure or safety.
Mutational profiling of mitochondrial DNA reveals an epithelial ovarian cancer‐specific evolutionary pattern contributing to high oxidative metabolism
Authors: Xie Fanfan , Guo Wenjie , Wang Xingguo , Zhou Kaixiang , Guo Shanshan , Liu Yang , Sun Tianlei , Li Shengjing , Xu Zhiyang , Yuan Qing , Zhang Huanqin , Gu Xiwen , Xing Jinliang , Liu Shujuan
Published: January 2024

Background

Epithelial ovarian cancer (EOC) heavily relies on oxidative phosphorylation (OXPHOS) and exhibits distinct mitochondrial metabolic reprogramming. Up to now, the evolutionary pattern of somatic mitochondrial DNA (mtDNA) mutations in EOC tissues and their potential roles in metabolic remodelling have not been systematically elucidated.

Methods

Based on a large somatic mtDNA mutation dataset from private and public EOC cohorts (239 and 118 patients, respectively), we most comprehensively characterised the EOC‐specific evolutionary pattern of mtDNA mutations and investigated its biological implication.

Results

Mutational profiling revealed that the mitochondrial genome of EOC tissues was highly unstable compared with non‐cancerous ovary tissues. Furthermore, our data indicated the delayed heteroplasmy accumulation of mtDNA control region (mtCTR) mutations and near‐complete absence of mtCTR non‐hypervariable segment (non‐HVS) mutations in EOC tissues, which is consistent with stringent negative selection against mtCTR mutation. Additionally, we observed a bidirectional and region‐specific evolutionary pattern of mtDNA coding region mutations, manifested as significant negative selection against mutations in complex V (ATP6/ATP8) and tRNA loop regions, and potential positive selection on mutations in complex III (MT‐CYB). Meanwhile, EOC tissues showed higher mitochondrial biogenesis compared with non‐cancerous ovary tissues. Further analysis revealed the significant association between mtDNA mutations and both mitochondrial biogenesis and overall survival of EOC patients.

Conclusions

Our study presents a comprehensive delineation of EOC‐specific evolutionary patterns of mtDNA mutations that aligned well with the specific mitochondrial metabolic remodelling, conferring novel insights into the functional roles of mtDNA mutations in EOC tumourigenesis and progression.
On the low‐frequency dispersion observed in dielectrophoresis spectra
Authors: Hughes Michael Pycraft , Clarke Krista S. P. , Hoque Rashedul , Griffiths Oreoluwa V. , Kruchek Emily J. , Bertagna Federico , Jeevaratnam Kamalan , Lewis Rebecca , Labeed Fatima H
Published: January 2024

The foundation of dielectrophoresis (DEP) as a tool for biological investigation is the use of the Clausius–Mossotti (C–M) factor to model the observed behaviour of cells experiencing DEP across a frequency range. Nevertheless, it is also the case that at lower frequencies, the DEP spectrum deviates from predictions; there exists a rise in DEP polarisability, which varies in frequency and magnitude with different cell types and medium conductivities. In order to evaluate the origin of this effect, we have studied DEP spectra from five cell types (erythrocytes, platelets, neurons, HeLa cancer cells and monocytes) in several conditions including medium conductivity and cell treatment. Our results suggest the effect manifests as a low‐pass dispersion whose cut‐off frequency varies with membrane conductance and capacitance as determined using the DEP spectrum; the effect also varies as a logarithm of medium conductivity and Debye length. These together suggest that the values of membrane capacitance and conductance depend not only on the impedance of the membrane itself, but also of the surrounding double layer. The amplitude of the effect in different cell types compared to the C–M factor was found to correlate with the depolarisation factors for the cells’ shapes, suggesting that this ratio may be useful as an indicator of cell shape for DEP modelling.
Investigation of interactions between biological thiols and gold nanoparticles by capillary electrophoresis with laser‐induced fluorescence
Authors: Dosedělová Věra , Kubáň Petr
Published: January 2024

Biological thiols spontaneously form a stable Au–S dative bond with gold nanoparticles (AuNP) that might be used for their selective extraction and enrichment in biological samples. In this work, interactions of selected biological thiols (glutathione, cysteine, homocysteine [Hcys], cysteamine [CA], and N‐acetylcysteine) with AuNP stabilized by different capping agents (citrate, Tween 20, Brij 35, CTAB, SDS) were investigated by UV–Vis spectroscopy and capillary electrophoresis with laser‐induced fluorescence. Spectrophotometric measurements showed aggregation of Hcys and CA with AuNP. In contrast, it was confirmed by CE‐LIF that biological thiols were adsorbed to all types of AuNP. Citrate‐capped AuNP were selected for AuNP‐based extraction of biological thiols from exhaled breath condensate (EBC). Dithiothreitol was utilized for desorption of biological thiols from the AuNP surface, which was followed by derivatization with eosin‐5‐maleimide and CE‐LIF analysis. AuNP‐based extraction increased the sensitivity of CE‐LIF analysis; however, further optimization of methodology is necessary for accurate quantification of biological thiols in EBC.
Experimental investigation of 4‐cylinder compression–ignition engine parameters fueled by newly formulated hydrous ethanol–diesel‐emulsified fuel infused with nano‐sized γ‐Al2O3 particles
Authors: Vasistha Vishal
Published: January 2024

The present study tested newly formulated hydrous ethanol–diesel‐emulsified fuel infused with nano‐sized γ‐Al2O3 particles on a turbocharged CRDI 4‐cylinder stationary diesel engine. W5H5, W5H10, and W10H5 test fuels were inducted into engine cylinders at a fixed engine speed of 2000 rpm. These test fuels significantly improved their physicochemical properties, with an 8.80% increase in gross calorific value and a 6.52% growth in cetane index. W5H10 exhibited a 16.01% increment in brake thermal efficiency and a 22.22% decrement in brake‐specific fuel consumption. Also, this fuel reported an 8.64% higher in‐cylinder pressure and a 40.71% higher heat release rate. W5H10 test fuel noted a 50% dip in carbon monoxide emissions and an 84.56% lower smoke opacity than diesel. W5H5 fuel reported 33.33% lower unburnt hydrocarbons than diesel at full load. W10H5 fuel observed an 88.46% drop in nitrogen oxide emissions compared with diesel at 10% engine load. The author found W5H10 the most suitable fuel for diesel engines with no modification costs.
Influence of state of charge inconsistency on electrical performance and thermal runaway characteristics in 2 serials 1 parallel lithium‐ion battery pack
Authors: Xie Zhongsheng , Wang Zhirong , Liu Jialong , Gao Tianfeng , Yan Wei
Published: January 2024

Lithium‐ion batteries (LIBs) are connected in series during use. State of charge (SOC) difference between two batteries will exist after charging/discharging owing to the capacity or resistance difference between them. This is also seen as SOC inconsistency. SOC inconsistency may cause battery electrical abuse. In this manuscript, a battery testing system, scanning electron microscope, heat furnace, and so on were employed to investigate the influence of SOC inconsistency on electrical performance and thermal runaway (TR) characteristics in 2 serials 1 parallel (2S1P) LIB pack after cycling. The results indicated that the cell with higher SOC in an inconsistent 2S1P pack was overcharged to 4.63 V during first charging, and the cell with lower SOC was over‐discharged to 1.90 V during first discharging. The cell with higher SOC became both overcharged and over‐discharged gradually with cycles. The cell with lower SOC became neither overcharged nor over‐discharged gradually. The electrical performance and TR characteristics of the cell with higher SOC became worse, while that of the cell with lower SOC did not change obviously. The state of health for cells with higher SOC decreased from 100% to 58% after 80 cycles. The time interval between current interrupt device activation and onset temperature of TR for cells with higher SOC was reduced by 183 s, and the maximum surface temperature increased by 34°C.
Phytochemical profile, nutritional composition of pomegranate peel and peel extract as a potential source of nutraceutical: A comprehensive review
Authors: Azmat Faiza , Safdar Mahpara , Ahmad Hajra , Khan Muhammad Rizwan Jamil , Abid Junaid , Naseer Muhammad Sadiq , Aggarwal Saurabh , Imran Ali , Khalid Urma , Zahra Syeda Mahvish , Islam Fakhar , Cheema Sadia Arif , Shehzadi Umber , Ali Rehman , Kinki Abdela Befa , Ali Yuosra Amer , Suleria Hafiz Ansar Rasul
Published: January 2024

The current study focuses on Punica granatum L. (pomegranate) peel and peel extract and their use as functional foods, food additives, or physiologically active constituents in nutraceutical formulations. The pomegranate peel extract is a good source of bioactive substances needed for the biological activity of the fruit, including phenolic acids, minerals, flavonoids (anthocyanins), and hydrolyzable tannins (gallic acid). The macromolecules found in pomegranate peel and peel extract have been recommended as substitutes for synthetic nutraceuticals, food additives, and chemo‐preventive agents because of their well‐known ethno‐medical significance and chemical properties. Moreover, considering the promises for both their health‐promoting activities and chemical properties, the dietary and nutraceutical significance of pomegranate peel and pomegranate peel extract appears to be underestimated. The present review article details their nutritional composition, phytochemical profile, food applications, nutraceutical action, and health benefits.
Schwann cell‐derived exosomes promote lung cancer progression via miRNA‐21‐5p
Authors: Zhou Yan , Zhang Yao , Xu Jianlin , Wang Yue , Yang Yu , Wang Weimin , Gu Aiqin , Han Baohui , Shurin Galina V. , Zhong Runbo , Shurin Michael R. , Zhong Hua
Published: January 2024

Schwann cells (SCs), the primary glial cells of the peripheral nervous system, which have been identified in many solid tumors, play an important role in cancer development and progression by shaping the tumor immunoenvironment and supporting the development of metastases. Using different cellular, molecular, and genetic approaches with integrated bioinformatics analysis and functional assays, we revealed the role of human SC‐derived exosomal miRNAs in lung cancer progression in vitro and in vivo. We found that exosomal miRNA‐21 from SCs up‐regulated the proliferation, motility, and invasiveness of human lung cancer cells in vitro, which requires functional Rab small GTPases Rab27A and Rab27B in SCs for exosome release. We also revealed that SC exosomal miRNA‐21‐5p regulated the functional activation of tumor cells by targeting metalloprotease inhibitor RECK in tumor cells. Integrated bioinformatic analyses showed that hsa‐miRNA‐21‐5p is associated with poor prognosis in patients with lung adenocarcinoma and can promote lung cancer progression through multiple signaling pathways including the MAPK, PI3K/Akt, and TNF signaling. Furthermore, in mouse xenograft models, SC exosomes and SC exosomal hsa‐miRNA‐21‐5p augmented human lung cancer cell growth and lymph node metastasis in vivo. Together our data revealed, for the first time, that SC‐secreted exosomes and exosomal miRNA‐21‐5p promoted the proliferation, motility, and spreading of human lung cancer cells in vitro and in vivo. Thus, exosomal miRNA‐21 may play an oncogenic role in SC‐accelerated progression of lung cancer and this pathway may serve as a new therapeutic target for further evaluation.
Side‐door temporoparietal fascia flap: First experience with a novel technique for anterior skull base reconstruction
Authors: Bresson Damien , Hudelist Benoit , Gaudioso Piergiorgio , Moya‐Plana Antoine , Herman Philippe , Idriceanu Tania , Nicolai Piero , Ferrari Marco
Published: January 2024

Background

Modern achievements in transnasal endoscopic skull base (SB) surgery have led to complex resections that render reconstruction a challenge. Temporoparietal fascia flap (TPFF) is a suitable option for SB reconstruction. The side‐door TPFF technique for anterior SB reconstruction is described here for the first time in a real‐life surgical setting.

Methods

Patients affected by a SB malignancy who underwent cranioendoscopic resection were included. For reconstruction, a multilayer reconstruction technique including side‐door TPFF transposition was employed.

Results

TPFF transposition was performed in five patients. The TPFF could be easily transposed via a side‐door approach. It adequately covered the edges of the defect and supported optimal healing of the surgical site. During follow‐up, vitality and integration of the TPFF were assessed endoscopically and radiologically.

Conclusions

The TPFF side‐door transposition technique is a valuable option in anterior SB reconstruction that can provide fast and effective healing, especially in patients needing adjuvant radiotherapy.
Operational status of mental health, substance use, and problem gambling services: A system‐level snapshot two years into the COVID‐19 pandemic
Authors: Hao Sherry , McLuhan Arthur , Moloney Gary , Kaur Nerinderjit , Moineddin Rahim , Turner Nigel E. , Matheson Flora I.
Published: January 2024

Background

The aim of this paper is to provide a system‐level snapshot of the operational status of mental health, substance use, and problem gambling services 2 years into the pandemic in Ontario, Canada, with a specific focus on services that target individuals experiencing vulnerable circumstances (e.g., homelessness and legal issues).

Methods

We examined data from 6038 publicly funded community services that provide mental health, substance use, and problem gambling services in Ontario. We used descriptive statistics to describe counts and percentages by service type and specialisation of service delivery. We generated cross‐tabulations to analyse the relationship between the service status and service type for each target population group.

Results

As of March 2022, 38.4% (n = 2321) of services were fully operational, including 36.0% (n = 1492) of mental health, 44.1% (n = 1037) of substance use, and 23.4% (n = 78) of problem gambling services. These service disruptions were also apparent among services tailored to sexual/gender identity (women/girls, men/boys, 2SLGBTQQIA + individuals), individuals with legal issues, with acquired brain injury, and those experiencing homelessness.

Conclusion

Accessible community‐based mental health, substance use and problem gambling services are critical supports, particularly for communities that have historically contended with higher needs and greater barriers to care relative to the general population. We discuss the public health implications of the findings for the ongoing pandemic response and future emergency preparedness planning for community‐based mental health, substance use and problem gambling services.
A systematic review of qualitative research on the self‐management experience of breast cancer patients
Authors: Sun Xi‐Bo , Su He‐Peng , Jiang He , Wang Bing , Lu Shuai , Qu Jin‐Xiu , Li Xiang‐Qi , Rao Ben‐Qiang
Published: January 2024

Objective

To integrate the qualitative research on the self‐management experience of breast cancer patients and conduct a systematic review of their self‐management experience.

Methods

Using a computer to search a series of databases such as CNKI, Wanfang, VIP, and China Biomedical Database, systematically collect and integrate qualitative research on the self‐management experience of breast cancer patients, and the search time is limited to January 2010 to December 2022. The qualitative research quality evaluation standard of the Joanna Briggs Institute Centre for Evidence‐Based Health Care in Australia was used as the evaluation standard of this project to complete the accurate evaluation of the literature; Meta‐analysis was used to complete the effective integration of the results.

Results

17 pieces of literature were included in this project, and 37 research results with strong integrity were extracted accordingly. On this basis, 7 different categories were summarised, and three integrated results were obtained: the experience of maintaining self‐management, symptom recognition, and self‐management.

Conclusion

In the different stages of self‐management of breast cancer patients, medical staff should give targeted guidance to help patients obtain a good prognosis.
Effect of fasedienol (PH94B) pherine nasal spray and steroidal hormones on electrogram responses and autonomic nervous system activity in healthy adult volunteers
Authors: Monti Louis , Hanover Rita , Salmán Ester , Baker Ross A. , Lappalainen Jaakko , Smith Mark
Published: January 2024

Objective

Fasedienol (PH94B) is a pherine compound formulated as a nasal spray that is hypothesized to regulate olfactory‐amygdala circuits of fear and anxiety. Fasedienol's effect on the local electrogram of nasal chemosensory neurons (EGNR) and autonomic nervous system (ANS) responses versus steroidal hormones and controls in healthy adults is reported.

Methods

Eight males and 8 females randomly received aerosolized control (propylene glycol) and study drugs (fasedienol, 17β‐estradiol, progesterone, cortisol, and testosterone, 0.4 μg each in propylene glycol) onto the nasal septum mucosal lining at 30‐min intervals over 2 sessions. EGNR was continuously monitored; autonomic parameters were recorded before and after administration.

Results

Fasedienol significantly increased EGNR amplitude (males: 5.0 vs. 0.6 mV, p < 0.001; females:5.7 vs. 0.6 mV, p < 0.001), and rapidly reduced respiratory rate (p < 0.05), heart rate (p < 0.01), and electrodermal activity (p < 0.05) versus control. EGNR and ANS responses after steroidal hormone administration were similar to control. 81% reported feeling less tense/more relaxed after receiving fasedienol, but not after receiving either control or steroidal hormones.

Conclusions

Intranasal fasedienol, but not control or steroidal hormones, activated EGNR and rapidly reduced ANS responses, consistent with sympatholytic effects. Combined with subjective reports, results suggest fasedienol may provide acute relief in anxiety conditions.