bluuebunny/crossref_metadata_2025_split huggingface dataset:
Jatrorrhizine Exhibits an Antitumor Effect Against Gefitinib‐resistant Non‐small Cell Lung Cancer via Inhibiting PI3K/mTOR Phosphorylation
Authors: Yao Kainan , Li Zeli , Muhetaer Gulizeba , Guan Huiting , Su Ming , Zhang Li , Liang Jian , Li Hang , Zhou Jihong 
Published: February 2025

ABSTRACTEpidermal growth factor receptor (EGFR) L858R/T790 M mutation‐mediated gefitinib resistance (GR) is a frequent dilemma in the treatment of non‐small cell lung cancer (NSCLC). This study aimed to explore the effect of jatrorrhizine on treating GR NSCLC and its possible mechanism of action. Cell viability, migration, invasion, and apoptosis detection were used to study the effect of jatrorrhizine on suppressing H1975 cells. Swiss Target Prediction and Traditional Chinese Medicine Database, GeneCards, and Online Mendelian Inheritance in Man databases and molecular docking were carried out to explore the targets of jatrorrhizine. Western blot was conducted to detect the effect of jatrorrhizine on inhibiting the PI3K/mTOR signaling pathway. Jatrorrhizine has a similar anti‐tumor effect on inhibiting the proliferation and migration of H1975 cells. Jatrorrhizine could dose‐dependently inhibit the proliferation, and invasion and promote the apoptosis of human NSCLC cells. The PI3K‐Akt signaling pathway was preliminarily predicted (Kyoto Encyclopedia of Genes and Genomes) and verified (Molecular docking) to be a critical pathway of jatrorrhizine against NSCLC. The cytotoxic assay of PI3K/mTOR inhibitor PKI‐402 on H1975 cells and ADP‐Glo Kinase assay of the inhibitory effect of jatrorrhizine on PI3K kinase activity. Western blot verified that jatrorrhizine down‐regulates the phosphorylation of PI3K/mTOR in H1975 cells. Our results revealed that jatrorrhizine is a potentially novel compound that inhibits GR NSCLC by inhibiting PI3K/mTOR phosphorylation.
Bacterial Profiling of Brined Grapevine Leaves Collected From Different Local Markets in Türkiye
Authors: Ucak Samet , Yegin Zeynep , Yurt Mediha Nur Zafer , Sudagidan Mert , Altunbas Osman , Ozalp Veli Cengiz 
Published: February 2025

ABSTRACTMicroorganisms linked to the grapevine, Vitis vinifera, can impact crop quality, plant growth, and human and plant health. This study examined the bacterial community structures of brined grapevine leaves (n = 56) taken from seven distinct regions in Türkiye using next‐generation sequencing technology. Investigations were also conducted into the samples' chemical properties. Firmicutes was the dominant phylum, followed by Proteobacteria, Actinobacteria, and Bacteroidetes. Bacillaceae was the predominant family in the analyzed samples, followed by Clostridiaceae, Peptostreptococcaceae, and Enterobacteriaceae. Bacillus was the dominant genus, followed by Lysinibacillus and Clostridium sensu stricto. The samples exhibited differences in terms of pH, total acidity, and salt content. The pH values of the brined grapevine leaves ranged from 2.31 to 6.91, the acidity levels ranged from 0.09% to 1.80%, and the salt percentages ranged from 3.39% to 49.14%. This research provides pioneering information for bacterial community analysis of brined grapevine leaves.
Green Microextraction, Paper‐Based Technique, and Smartphone Sensing for Sustainable Determination of Nicotinamide in Pharmaceuticals and Blood Samples
Authors: Ali Diyar Salahuddin , Othman Hazha Omar , Hassan Rebwar Omar 
Published: February 2025

ABSTRACTThis study presents the development of two simple, sensitive, and selective microextraction and preconcentration procedures for determining nicotinamide (NAM) in pharmaceutical formulations and blood samples. The methods utilize the König reaction, where cyanogen chloride, formed by reacting potassium thiocyanate with sodium hypochlorite in an acidic medium, interacts with NAM and couples with buffered barbituric acid at pH 3.5 to form a pink polymethine dye. This dye is extracted into an isobutanol layer using tetrabutylammonium bromide and exhibits maximum absorption at 560 nm for spectrophotometric quantification. In the smartphone paper‐based (SPB) method, the dye is applied to a paper strip, captured by a smartphone, and analyzed for red, green, and blue components. Both methods were thoroughly evaluated for key parameters, demonstrating adherence to Beer's law over a NAM concentration range of 1.0–7.8 µg/mL, with limits of detection of 0.76 µg/mL for the spectrophotometric method and 0.91 µg/mL for the SPB method. Our SPB combines paper‐based analysis, smartphone detection, and microextraction for the first time, offering a cost‐effective, portable, and sensitive solution for NAM assay in plasma. A comparison with the established high‐performance liquid chromatography method, using statistical tests, showed no significant differences, confirming the reliability of these novel methods.
Protective Effect of Carvedilol Against Oxidative Stress Induced by Palmitic Acid in Primary Rat Hepatocytes
Authors: Salas Sandra A. Serna , Damba Turtushikh , Buist‐Homan Manon , Moshage Han 
Published: February 2025

ABSTRACTHepatocyte lipotoxicity (HL) is an important factor in the pathogenesis of Metabolic Dysfunction‐Associated Steatotic Liver Disease (MASLD). It is defined as the detrimental effects of exposure to (excessive) amounts of toxic lipid species, leading to increased mitochondrial β‐oxidation, oxidative stress (OxS), and organellar dysfunction. Carvedilol (CV) is a β‐adrenergic blocker with antioxidant properties. To elucidate whether CV protects hepatocytes against lipotoxicity induced by palmitic acid (PA) by reducing OxS and endoplasmic reticulum (ER) stress. Primary rat hepatocytes (rHep) were used. Lipotoxicity was induced by PA (1 mmol/L). Cell damage was evaluated by Sytox Green staining. Mitochondrial generation of reactive oxygen species (mROS) was assessed by MitoSox. mRNA and protein expression were measured by qPCR and Western blot, respectively. Lipid accumulation was measured by Oil Red O staining and triglyceride (TG) content. PA induced cell death in > 80% of cells and increased mROS generation. PA increased mRNA expression of ER stress markers CHOP and sXBP1 and slightly increased lipid accumulation. Expression of the β‐oxidation‐related gene Cpt1a was increased. CV (10 µmol/L) significantly reduced PA‐induced cell death to control levels (< 8% of total cells), and mROS generation and expression of the mitochondrial antioxidant enzymes Sod2 and Cat were increased by 40% by CV in the presence of PA. CV did not change the expression of ER stress markers. CV, added before PA, protects rHep against PA‐induced cytotoxicity by reducing OxS and increasing the expression of antioxidant enzymes without any additional protective effect on ER stress or lipid accumulation.
Boronic Acid‐Linked Apo‐Zinc Finger Protein for Ubiquitin Delivery in Live Cells
Authors: Ghosh Pritam , Seitz Oliver 
Published: February 2025

AbstractDelivering cargo into live cells has extensive applications in chemistry, biology, and medicine. Cell‐penetrating peptides (CPPs) provide an ideal solution for cellular delivery. Enhancing CPPs with additional functional units can improve delivery efficiency. We investigate the conjugation of boronic acid modules to enhance internalization through interactions with cell surface glycans. The aim of this study is to determine whether adding boronic acid can transform a peptide that typically lacks CPP properties into one that functions as a CPP, enabling the delivery of crucial biological cargo like ubiquitin (Ub). The zinc finger protein in its apo state was selected as a “boronate‐enabled” CPP. Results indicate that skeletal point mutations and post‐synthetic modifications, combined with conjugated benzoboroxole derivatives, enable the apo‐ZFP the ability to transport Ub within A549 cells, confirmed through microscopy and flow cytometry. This effective internalization of cargo offers valuable insights for advancing the development of boronic acid‐mediated cell‐penetrating peptides.
Regulation of N‐Glycosylation of CDNF on Its Protein Stability and Function in Hypoxia/Reoxygenation Model of H9C2 Cells
Authors: Huang Qingwen , Dong Haibin , Jia Wenjuan , Ren Yanxin , Li Wei , Zhong Lin , Gong Lei , Yang Jun 
Published: February 2025

ABSTRACTMyocardial ischemia–reperfusion (I/R) injury is a cause of high post‐interventional mortality in patients with acute myocardial infarction (MI). Cerebral dopamine neurotrophic factor (CDNF) is an endoplasmic reticulum (ER) resident protein, and its expression and secretion are induced when tissues and cells are subjected to hypoxia, ischemia, or traumatic injury. As a novel cardiomyokine, CDNF plays a crucial role in the progression of myocardial I/R injury. In our previous study, we reported that the overexpression of CDNF inhibited tunicamycin‐induced H9C2 cell apoptosis. Moreover, there is a unique N‐glycosylation site at Asn57 in the CDNF protein, which likely affects its function in H9C2 cells. However, the detailed impact remains unexplored. In our current study, we observed elevated levels of CDNF in the serum of acute MI patients, myocardial tissue of I/R model mice, and H/R model H9C2 cells. To detect the effect of N‐glycosylation on the CDNF protein, we constructed an Asn57 mutant (N57A) plasmid and found that the N57A protein presented similar intracellular localization to those of the wild‐type CDNF protein. However, the N57A protein demonstrated reduced stability, and the mutant protein could not protect H/R‐induced H9C2 cells from apoptosis. Moreover, this process may occur through the downregulation of the PI3K/Akt pathway. Therefore, N‐glycosylation of CDNF may be essential for protein stability and its protective role in H/R injury in H9C2 cells.
A Small Cut, a Big Challenge: Pediatric Mucormycosis in an Unexpected Host
Authors: Tanvir Marriam , Tanvir Ali , Khan Saad , Henna Fathimathul , Fatima Syeda Mashal , Munir Aqsa , Iqbal Javed 
Published: February 2025

ABSTRACTMucormycosis is an infrequent fungal infection commonly seen in immunocompromised individuals. However, it can also occur in immunocompetent patients, especially following trauma. We present a case of a 15‐month‐old girl with increasing swelling and redness in her left eye after a minor traumatic injury. Imaging showed sinusitis with orbital involvement. Histopathology validated the diagnosis of mucormycosis caused by Rhizopus species. The patient had emergency surgery, followed by antifungal and antibiotic therapy. Despite febrile reactions to the treatment, the infection was managed, and the patient was discharged after 2 months. This case highlights the importance of considering mucormycosis in immunocompetent patients with unexplained ocular symptoms after trauma. Early diagnosis and aggressive treatment are essential for improving outcomes, especially in pediatric patients.
A Case Report of Neuromyelitis Optica Spectrum Disorder (NMOSD) Treatment in Resource‐Limited Setup: An Ethiopian Experience
Authors: Mulate Sebhatleab T. , Molla Bereket A. , Abera Berhanu M. , Hailemariam Tseganesh M. , Zewde Yared Z. 
Published: February 2025

ABSTRACTMOSD is a rare and disabling immune‐mediated inflammatory Astrocytopathic disease characterized by demyelination and axonal destruction, typically involving the spinal cord and the optic nerve. Here we present a case report of a 53‐year‐old female patient who had a pertinent history of treatment for optic neuritis a few months back, currently diagnosed with Neuromyelitis Optica after she presented with a three‐week history of weakness of lower extremity, headache, and neuropathic pain. She was pulsed with methylprednisolone and started on azathioprine, which significantly improved her clinical condition. When patients with optic neuritis and transverse myelitis occur, a high index of suspicion for NMOSD is essential. Establishing a diagnosis based on clinical and MRI findings is crucial for initiating therapy quickly, halting more harm, and avoiding a delay in diagnosis. Our experience treating our patient shows that Azathioprine is still a practical choice in resource‐limited setups.
Brainwave Activity Localization, Mood Symptoms, and Balance Impairment in a Male South African Rugby Player With Persisting Symptoms After Concussion: A Case Report
Authors: Lumb M. J. , Snegireva N. , Coetzee A. M. , Welman K. E. 
Published: February 2025

ABSTRACTThe case sets the foundation for clinical protocols to incorporate mobile EEG and qEEG techniques, instrumental balance testing, and mood symptom screening in athletes who have suffered a sports‐related concussion. The protocol provides a framework for clinicians to monitor a patient's recovery progress in terms of brainwave activity, general cognition, moods, and motor control. Objective data obtained through the protocol may assist in developing personalized treatment plans, improving follow‐up care, and identifying residual brain function deficits that may be missed in standardized clinical exams. Finally, this case highlights a need for more thorough communication and testing procedures that screen for mood symptoms and provide an opportunity for athletes to discuss their mental health after suffering from an SRC.
Acid And Base Catalyzed Reaction Mechanisms in Bio Butadiene Production From 2,3‑Butanediol
Authors: Bekele Beruk A. , Poissonnier Jeroen , Thybaut Joris 
Published: February 2025

2,3‐butanediol (2,3‑BDO) dehydration to 1,3‑butadiene (BD) is assessed over a Sc2O3 catalyst calcined at 800°C (Sc2O3_800) and compared with performance of an in‑house prepared ZrO2 (ZrO2_HT_800) catalyst via active sites, activity, product distribution and apparent activation energies to elucidate the reaction mechanism. Sc2O3_800 achieved 40% (mol mol‐1) selectivity towards BD at complete 2,3‑BDO conversion. This is due to its medium strength basic sites and weak acid sites, favoring a base‑dominated mechanism and producing 3‑buten‑2‐ol (3B2OL) as the primary product, suggesting an E1cb‐like mechanism. Conversely, ZrO2_HT_800 favors methyl ethyl ketone (MEK) formation due to relatively similar amounts and strength of acid and base sites, suggesting competing E1 and E2 mechanisms. Apparent activation energies for 3B2OL formation amount to 63 kJ mol‐1 on the Sc2O3_800 catalyst and 38 kJ mol‐1 on the ZrO2_HT_800 catalyst, while MEK formation has an apparent activation energy of 64 kJ mol‐1 in Sc2O3_800 and 80 kJ mol‐1 in ZrO2_HT_800 catalysts. The optimal process conditions for bio‐butadiene production in a single step over Sc2O3_800 are a temperature of 385°C, inlet 2,3‑BDO partial pressure of 0.2 bar and a space time amounting to 1130 kg s mol‑1.
Aptamer‐Driven Biosensor Technology for the Quantitative Analysis of C‐Reactive Protein
Authors: Oranzie Marlon , January Jaymi L. , Sanga Nelia A. , Leve Zandile D. , Mini Sixolile , Cupido Candice , Douman Samantha F. , Iwuoha Emmanuel I. 
Published: February 2025

AbstractC‐reactive protein (CRP) is a widely recognized biomarker for early myocardial infarction (MI) detection, released into the bloodstream during heart inflammation. Traditional assays for CRP detection, like ELISA and immunoradiometric assays, are costly, time‐consuming, and require large sample volumes. Aptasensors are becoming increasingly popular for MI diagnosis due to their affordability, simplicity, and potential for point‐of‐care use. In this study, an electrochemical aptasensor incorporating mercaptosuccinic acid‐capped nickel selenide quantum dots (MSA‐NiSe2 QD) were developed for CRP detection. The amine‐modified aptamer was immobilized on the MSA‐NiSe2 QD using EDC/NHS coupling chemistry. Chronocoulometric measurements showed high selectivity towards CRP in phosphate buffer, with a linear range of 10–110 pg/mL and a detection limit of 2.80 pg/mL. Cross‐reactivity experiments confirmed the aptasensor's high selectivity for CRP. Testing in human serum samples demonstrated recovery rates of 94–100.5 %, indicating its suitability for clinical diagnostics. Validation studies with a commercial CRP ELISA kit showed the aptasensor's superior sensitivity in both physiological buffer and human serum.
Abiotic Ribonucleoside Formation in Aqueous Microdroplets: Mechanistic Exploration, Acidity, and Electric Field Effects
Authors: Piejko Maciej , Alfonso‐Ramos Javier E. , Moran Joseph , Stuyver Thijs 
Published: February 2025

AbstractAqueous microdroplets have been reported to dramatically increase the rate of chemical reactions. Proposed mechanisms for this acceleration include confinement effects upon droplet evaporation, and Brønsted acid or electric field catalysis at the air‐water interface. However, computational investigations indicate that the operation of these mechanisms is reaction‐dependent, with conclusive evidence for a role for electric field catalysis still lacking. Here, we present a computational investigation of the reported abiotic phosphorylation of ribose and the subsequent formation of ribonucleosides, focusing on acidity and oriented external electric field (OEEF) effects. The most plausible reaction mechanism identified involves the protonation of ribose, followed by carbocation formation and an SN2 substitution step. Without an OEEF, all considered pathways are thermally inaccessible. However, in the presence of a significant OEEF, the SN2‐based pathway, leading to the β‐ribonucleoside isomer, becomes highly stabilized, reducing the energetic span to a thermally accessible 12–13 kcal/mol. Surprisingly, the OEEF‐mediated reaction closely mirrors the enzymatic mechanism of phosphorolysis via SN2 substitution, including a pronounced anomeric selectivity. Our results support the hypothesis that some reactions in aqueous microdroplets are accelerated by electric fields and provide further evidence for the importance of electrostatic catalysis in biological systems, particularly for phosphorylase enzymes.
Dual‐Functional Synthetic Linear and Cyclic Peptides with Anti‐Amyloid and Antimicrobial Activities for Alzheimer's Disease
Authors: Yang Lujuan , Wang Yao , Shang Peng , Ma Gang 
Published: February 2025

AbstractDual‐functional peptides exhibiting both anti‐amyloid and antimicrobial activities have attracted attention as promising candidates for Alzheimer's disease treatment. The advantage of these peptides lies in their ability to simultaneously target both the amyloid cascade hypothesis and the microbial infection hypothesis, in contrast to single‐function inhibitors. However, most of the reported dual‐functional peptides to date are natural peptides, and the development of synthetic peptides in this area remains limited. In this study, we propose two strategies to aid in the discovery of synthetic dual‐functional peptides. We then report four distinct synthetic dual‐functional peptides identified using these strategies, with the Aβ1–40/Aβ1–42 fibrillation system and common bacterial strains serving as a proof‐of‐concept platform. One strategy involves repurposing existing knowledge, while the other breaks from established conventions. Using the first strategy, we discovered a very short dual‐functional linear peptide. With the second strategy, we identified a simple dual‐functional cyclic peptide. Furthermore, by combining these two strategies, we developed a hybrid dual‐functional peptide incorporating both linear and cyclic structures. We hope that our findings will contribute to the future discovery of more synthetic dual‐functional peptides for treating Alzheimer's disease.
Biocatalytic Stereodivergent Synthesis of Substituted Tetrahydro‐Benzo‐(Oxa, Thia, and Di)‐Azepines
Authors: Manna Tanaya , Das Piyal , Rabbani Aniqah , Beyer Frederike , Merten Christian , Masood Husain Syed 
Published: February 2025

AbstractBenzo‐fused seven‐membered N,O‐, N,S‐ and N,N‐containing heterocyclic moieties are found in several marketed drugs and biologically active molecules. However, the asymmetric synthesis of such heterocycles is limited to the use of transition metal catalysts or chiral phosphoric acids. In the current work, imine reductases (IREDs) are utilized to develop a general biocatalytic method for the stereodivergent synthesis of 5‐substituted tetrahydro‐1,4‐benzoxazepines, 4‐substituted tetrahydro‐1,5‐benzothiazepines, and 2,2,4‐trisubstituted tetrahydro‐1,5‐benzodiazepines in excellent yields (up to 96 %), enantiomeric excess (up to >99 %) and diastereoselectivity (up to >99 %). In addition, imine reductase assisted reductive amination gave facile access to 2,4‐disubstituted tetrahydro‐1,5‐benzodiazepines starting from 1,3‐diketone and 1,2‐diamino benzene with excellent stereoselectivity and high yields. The absolute configuration of the newly synthesized N‐heterocycles was determined using vibrational circular dichroism (VCD). The presented methodology has further broadened the scope of IREDs towards the preparation of chiral seven‐membered N‐heterocycles containing another heteroatom.
Peripheral Modification Strategy of Heavy Atom for High‐Performance Multi‐Resonance Thermally Activated Delayed Fluorescence Emitters
Authors: Wan Liang , Cheng Zhuang , Ma Xiaobo , Jiang Yixuan , Yan Zhenyu , Yan Yan , Su Zihan , Liu Futong , Lu Ping 
Published: February 2025

AbstractOrganic light‐emitting materials with multi‐resonance thermally activated delayed fluorescence (MR‐TADF) have shown great potential for realizing highly efficient narrowband organic light‐emitting diodes (OLEDs). However, the heavy efficiency roll‐off caused by the slow reverse intersystem crossing (RISC) process remains a challenging issue for the further practical application of MR‐TADF materials. Here, we develop two TADF emitters, BNDBT and BNDBF, in which the dibenzothiophene and dibenzofuran substituents are attached at the bottom of the B/N frameworks. They all exhibit the similar high photoluminescence quantum yields of 90 % and 87 %. The sulfur‐containing material BNDBT exhibits a RISC rate (kRISC) of 6.02×104 s−1, which is three‐folded higher than BNDBF (2.09×104 s−1) without heavy atom. The corresponding green OLED based on BNDBT exhibits an improved external quantum efficiency of 35.5 % and lower efficiency roll‐offs at high brightnesses of 100 cd m−2 and 1000 cd m−2, respectively. In addition, the BNDBT‐based OLED maintains high color purity without causing a sharp increase in FWHM as compared with that of BNDBF. This work indicates that introducing the heavy atom at the bottom of the B/N skeleton is an effective strategy to enhance kRISC while maintaining narrow FWHM, thereby achieving high‐performance MR‐TADF emitters.
What influences family satisfaction?
Authors: Neneh Brownhilder N. , Welsh Dianne H. B. 
Published: February 2025

AbstractWork–family enrichment has attracted interest from the perspective of the individual, entrepreneur, and family business. This study investigates how family–work enrichment (FWE) influences Family satisfaction (FS), the moderating role of family ownership, and the three‐way interaction between FWE, FS and gender, which provides a more synergistic understanding of family businesses. In a sample from four South African provinces, this study shows that FWE has a positive association with FS and that family ownership moderates the association between FWE and FS. The effect is more pronounced in families than in non‐family businesses. The three‐way interaction among FWE, family ownership, and gender is significantly associated with FS, but the effect is more substantial for women in non‐family businesses; only male entrepreneurs in family businesses benefit from family resources. The study concludes with implications for practice.