bluuebunny/crossref_metadata_2025 huggingface dataset:
Striking Impact of Solvent Polarity on the Strength of Hydrogen‐Bonded Complexes: A Nexus between Theory and Experiment
Authors: Lo Rabindranath , Manna Debashree , Vacek Jaroslav , Bouř Petr , Wu Tao , Osifová Zuzana , Socha Ondřej , Dračínský Martin , Hobza Pavel
Published: December 2024

The binding free energy of hydrogen‐bonded complexes is generally inversely proportional to the solvent dielectric constant. This occurs because the solvent‐accessible surface area of the complex is always smaller than that of the individual subsystems, leading to a reduction in solvation energy. The present study explores the potential for stabilizing hydrogen‐bonded complexes in a solvent with higher polarity. Contrary to the established understanding, we have demonstrated that the hydrogen‐bonded complex (CH₃CH₂COOH∙∙∙2,4,6‐trimethylpyridine) can be better stabilized in a solvent with higher polarity. In this case, a significant charge transfer between the subsystems results in an increased dipole moment of the complex, leading to its stabilization in a more polar solvent. The expected inverse relationship between binding free energy and solvent dielectric constant is observed when the charge transfer between the subsystems is low. Thus, the magnitude of the charge transfer between subsystems is possibly the key factor in determining the stabilization or destabilization of H‐bonded complexes in different solvents. Here, we present a comprehensive study that combines experimental and theoretical approaches, including nuclear magnetic resonance (NMR), infrared (IR) spectroscopies and quantum chemical calculations to validate the findings.
DNA Mimic Foldamer Recognition of a Chromosomal Protein
Authors: Deepak Deepak , Wu Jiaojiao , Corvaglia Valentina , Allmendinger Lars , Scheckenbach Michael , Tinnefeld Philip , Huc Ivan
Published: December 2024

Helical aromatic oligoamide foldamers bearing anionic side chains that mimic the overall shape and charge surface distribution of DNA were synthesized. Their interactions with chromosomal protein Sac7d, a non‐sequence‐selective DNA‐binder that kinks DNA, were investigated by Surface Plasmon Resonance (SPR), Isothermal Titration Calorimetry (ITC), Circular Dichroism spectroscopy (CD), melting curve analysis, Atomic Force Microscopy (AFM), and Nuclear Magnetic Resonance (NMR), as well as by single crystal X‐ray crystallography. The foldamers were shown to bind to Sac7d better than a DNA duplex of comparable length. The interaction is diastereoselective and takes place at the DNA binding site. Crystallography revealed that the DNA mimic foldamers have a binding mode of their own and that they can bind to Sac7d without being kinked.
Low‐Dimensional Lead‐Free Metal Halides for Efficient Electrically Driven Light‐Emitting Diodes
Authors: Yao Jia‐Yu , Liu He , Chen Zhong‐Ning , Ma Biwu , Xu Liang‐Jin
Published: December 2024

Electrically driven light‐emitting diodes (ED LEDs) based on 3D metal halide perovskites have seen remarkable advancements during the past decade. However, the highest‐performing devices are largely based on lead‐containing 3D perovskites, presenting two key challenges – toxicity and stability – that must be addressed for commercialization. Reducing structural dimensionality and incorporating non‐lead metals present promising pathways to address these issues. Although research on ED LEDs based on low‐dimensional, lead‐free metal halides (LD LFMHs) is growing, their performance still significantly lags behind that of 3D lead halide perovskites. This review seeks to deliver a comprehensive overview of ED LEDs based on LD LFMHs, covering a brief history of their development, methods for material synthesis, luminescence mechanisms, and applications in electroluminescent devices. It also examines current challenges and proposes practical strategies to enhance device performance, with the goal of inspiring further progress in the field.
Molecular Customization of Anode‐Electrolyte Interfaces for Enhanced Stability and Reversibility in Aqueous Zinc‐Carbon Capacitors
Authors: Xu Yang , Chen Jingzhu , Li Tao , Ma Hexian , Lv Zhuoran , Zhang Shicong , Bi Hui , Huang Fuqiang , Lin Tianquan
Published: December 2024

Aqueous zinc‐carbon capacitors display application potential in green power and high‐end equipment owing to their high security, large power and sustainability. The water‐rich zinc anode‐electrolyte interface (AEI) and disordered zinc‐ion diffusion are the culprits triggering corrosion reactions and dendrite growth, threatening the sustainability of aqueous zinc‐carbon capacitors. Herein, a polyfunctional biomolecular, vitamin B6, is introduced into the traditional aqueous electrolyte for customizing the functional AEI and fine‐regulating the interfacial coordination environment of zinc ions. Specifically, the preferential anchoring of pyridine nitrogen enables trace vitamin (2.0 g L−1) to construct a robust AEI and suppress corrosion reactions. The hydroxyl function zone provides high‐octane guidance for zinc‐ion diffusion at the AEI, resulting in flat zinc (002) oriented growth. Consequently, the Zn//Zn symmetrical cell features an ultrahigh cumulative capacity of 4.0 Ah cm−2 under 34 % depth of discharge. The vitamin‐optimized zinc‐carbon capacitor features extended operational lifetimes exceeding 8 months (200 thousand cycles at 5.0 A g−1), and demonstrates a high areal capacity of averaging 0.68 mAh cm−2 and exceptional durability over 2000 hours at 1.0 A g−1 under a high discharge depth of zinc anode (averaging 11.6 %). This work offers valuable insights into sustainable and cost‐effective zinc‐carbon capacitors.
Poly(2‐Hydroxymethyl‐2‐Oxazoline) as Super‐Hydrophilic Antifouling Polymer
Authors: Jana Somdeb , Roels Milan , Leiske Meike N. , Bernhard Yann , De Geest. Bruno G. , Van Hecke Kristof , Hoogenboom Richard
Published: December 2024

Non‐ionic “super‐hydrophilic” polymers generally possess strong non‐fouling characteristics and, therefore, can suppress non‐specific and unwanted interactions with blood proteins when attached to in vivo nanomedicine ranging from drug or gene delivery to diagnostics. In this contribution, we revitalize a protected alcohol functionalized 2‐oxazoline monomer, 2‐acetoxymethyl‐2‐oxazoline, that was first reported almost fifty‐five years ago and explore the possibility of making “super‐hydrophilic” poly(2‐oxazoline)s for biomedical applications. The synthesis of the 2‐acetoxymethyl‐2‐oxazoline monomer and its cationic ring‐opening homopolymerization and copolymerization kinetics are reported. The monomer showed unanticipated and intriguing reactivity during homopolymerization as it very slowly polymerizes at low temperature while the polymerization rate constant at high temperature is amongst the highest known values. Additionally, first order kinetic plots for the copolymerisation of AcOMeOx with EtOx at high temperature revealed that AcOMeOx is incorporated at a slower rate than EtOx confirming its lower nucleophilicity, while EtOx was accelerated in the copolymerization indicating chain‐end activation by the ester side‐chains. Subsequently, controlled hydrolysis of the resulting poly(2‐acetoxymethyl‐2‐oxazoline) (PAcOMeOx) generates the alcohol (−OH) side chain functional poly(2‐hydroxymethyl‐2‐oxazoline) (PHOMeOx). The relative hydrophilicity of PHOMeOx was analyzed and compared with the previously reported most hydrophilic poly(2‐oxazoline)s, such as poly(2‐methoxymethyl‐2‐oxazoline) and poly(2‐methyl‐2‐oxazoline), revealing that PHOMeOx is the most hydrophilic poly(2‐oxazoline) reported to date. Finally, the cytocompatibility of these different hydrophilic polymers with MDA‐MB‐231 breast cancer cells was explored where all polymers revealed high cytocompatibility. Most importantly, strong anti‐fouling properties of the most hydrophilic PHOMeOx against serum protein were observed during the cell association studies. Hence, the “super‐hydrophilic” and anti‐fouling PHOMeOx might be an interesting candidate to be explored in the area of polymeric drug and gene delivery as well as anti‐fouling surfaces.
Optical Properties and Performance of Pristine and Ag‐Doped ZnO as Working Electrode in Dye‐Sensitized Solar Cells
Authors: Sharif Abdul M. , Ashrafuzzaman Md. , Kalam Abul , Al‐Sehemi Abdullah G. , Yadav Pankaj , Tripathi Brijesh , Dubey Mrigendra , Assiri Mohammad A. , Du Gaohui
Published: December 2024

Dye‐sensitized solar cell (DSSC) is a potential low‐cost solar energy conversion device that is simple to fabricate with low cost than traditional silicon‐based solar cells. The development of DSSC is hampered by the limitations of using ZnO‐based photoanodes for a number of reasons (e.g., charge recombination, efficiency and expensive method). Photoanode material is one of the crucial components in DSSC, which plays a vital role in overall device performance, and the improvement of photoanode materials is needed. This work is focused to improve the overall performance of DSSCs with reducing problem by incorporating a dopant into ZnO semiconductor material as photoanode. Pristine and silver‐doped zinc oxide (Ag‐ZnO) photoanodes with various weight percentages of Ag (2, 3 and 4 wt%) were prepared by a facile, cost‐effective and quick green‐modified–solvothermal method with diethylamine (precipitating agent) and fig leaf extract (capping agent). The structural, crystalline nature, morphological and optical properties of prepared nanomaterials were analysed using X‐ray diffraction (XRD), field emission scanning electron microscopy (FE‐SEM) and UV–Vis spectrophotometry. The results revealed that the crystallite size of pristine and Ag‐ZnO with 2, 3 and 4 wt% of Ag decreased from 85 to 21 nm by increasing the percentage of Ag. The surface roughness decreased with increasing the weight percentage of Ag, and there is no big change in their morphology. The energy band gaps (Eg) of pristine and Ag‐ZnO with 2%, 3% and 4% Ag determined by Tauc plot were 2.55, 3.05, 3.09 and 3.17 eV, respectively. Among the pristine and Ag‐doped ZnO fabricated devices, the photovoltaic measurements of 4% Ag‐ZnO exhibited superior performance reaching the highest efficiency of 2.25% with a short‐circuit current density (JSC) of ~5.8 mA/cm2, an open‐circuit voltage (VOC) of ~810 mV and a fill factor (FF) of ~0.54, which might be due to large optical band gap, better conductivity, reduced recombination rate and enhanced dye adsorption.
A First Report of Docosahexaenoic Acid‐Clocked Polymer Enveloped Gold Nanoparticles: A Way to Precision Breast Cancer and Triple Negative Breast Cancer Therapy and Its Apoptosis Induction
Authors: Khanna Lalit , Ballal Suhas , Awasthi Kumud Kant , Singh Dhiraj , Chinnathambi Arunachalam , Alahmadi Tahani Awad , Abudoleh Suha Mujahed , Thangavelu Indumathi
Published: December 2024

Functionalized gold nanoparticles (GNPs) are extensively utilized in various disciplines due to their excellent bioactivity, biocompatibility, and extended drug half‐life, influenced by the ligands and size that are changed on surfaces. In this study, we successfully fabricated GNPs coated with ligands containing docosahexaenoic acid (DHA) and polyethylene glycol (PEG) clocked by a carboxyl group. These nanoparticles are referred to as MPA@GNPs‐PEG‐DHA. The cytotoxicity results demonstrate that MPA@GNPs‐PEG‐DHA exhibits superior cell selectivity, explicitly inhibiting the proliferation of breast cancerous cells than noncancerous cell lines. Apoptosis is involved in the reduction of cell proliferation by MPA@GNPs‐PEG‐DHA, as demonstrated clearly through many assays measuring apoptotic index, including AO/EB staining, DAPI, annexin V‐FITC staining, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) measurement. The efficacy of MPA@GNPs‐PEG‐DHA in inducing apoptosis was demonstrated by its inhibition of mitochondrial dysfunction by ROS. MPA@GNPs‐PEG‐DHA has the potential to improve the induction of apoptosis in breast cancerous cells.
Expert Perspective: Management of Relapses in Giant Cell Arteritis
Authors: Alba Marco A. , Unizony Sebastian , Warrington Kenneth J. , Murgia Giuseppe , Prieto‐González Sergio , Salvarani Carlo , Matteson Eric L. , Kermani Tanaz A.
Published: December 2024

Giant cell arteritis (GCA) is a relapsing large vessel vasculitis with risk of serious ischemic manifestations, including vision loss and vascular damage in the form of large artery stenosis, aneurysms, and dissections. Approximately 50% of patients treated with glucocorticoid (GC) monotherapy and 30% of patients receiving adjunctive therapy with tocilizumab experience disease relapses, often during the first 2 years after diagnosis. Although most relapses in GCA do not involve life‐ or organ‐threatening presentations and can be controlled successfully, frequent relapses may lead to increased prescription of GC and consequent treatment‐related morbidity, in addition to risk of further vascular damage. Emerging data suggest that persistent disease activity may lead to increased vascular morbidity. Additionally, although tocilizumab decreases the frequency of relapses, more than 50% of patients relapse after discontinuation of therapy. Therefore, although interleukin‐6 blockade suppresses disease activity, it does not restore tolerance. In this article, we discuss the practical diagnosis and management of GCA relapses from an expert perspective. Current treatment options for GCA relapses, including those recommended by international guidelines, and novel potential therapies are reviewed.
Structural Variation In β‐Octamolybdate Polyoxoanion Based Crystals Across Lanthanide Series Isolated From A Water/DMSO Solution.
Authors: Tewari Shailabh , Ramanan Arunachalam
Published: December 2024

The crystallization of lanthanide‐containing β‐octamolybdate (β‐{Mo8O26}4‐) based solids from a binary 1:1 (water/DMSO) solution under ambient conditions is reported. A uniform synthetic protocol yielded three structurally related series of general composition {Ln(solvent)n}[NaMo8O26]·yH2O, with the whole lanthanide series (except for radioactive Pm). The three series are (i) {Ln(DMSO)8}[NaMo8O26]·0.5H2O, Ln= La, Ce, Pr, Nd and Sm (Series C1); (ii) {Ln(DMSO)6(H2O)2}[NaMo8O26] for Ln= Eu, Gd, Tb, Dy and Ho (Series C2) and (iii) [{Ln(DMSO)7}][NaMo8O26]·H2O for Ln= Dy, Ho, Er, Tm, Yb and Lu (Series C3). All solids reported here contain [−β‐Mo8O26−Na−β‐Mo8O26−] anionic chains, which is the dominant feature in the crystal packing of these solids. The chains interacted via hydrogen bonds with the solvated lanthanide counter cations. Lanthanide contraction brings about the difference in the primary coordination sphere of the Ln3+ cations in the three series reported here. This manifests in the crystal structure as a change in the relative orientation of chains (or clusters) and the position of Ln3+ centers, with water acting as the structure director. The study demonstrates Nature’s parsimonious ability to optimize intermolecular interactions via diminutive deviations from recognizable packing patterns when a crystal nucleates from solution.
Recent Advances on Integrating Porous Nanomaterials with Chemiluminescence Assays
Authors: Cao Yue , Wu Ming , Cao Yu , Zhu Wenlei , Zhou Yang
Published: December 2024

Advanced porous nanomaterials have recently been the subject of considerable interest due to their high surface areas, tunable pore structures, high porosity, and ease of modification. In the chemiluminescence (CL) domain, the incorporation of additional pores into nanostructures not only enhances the loading capacity for signal amplification but also allows the confinement effect in a nanoscale microreactor and the controlled release of reaction agents. In light of this, increasing efforts have been made to fabricate various porous nanomaterials and explore their potential applications in CL assays. This review therefore aims to highlight the recent advances in preparation strategies and basic attributes of the CL‐related porous nanomaterials. Moreover, it offers a comprehensive summary of the emerging CL sensing applications based on these materials. The key challenges and future perspectives of porous nanomaterials in CL assays are finally discussed.
On the Equivalence of Likelihood‐Based Confidence Bands for Fatigue‐Life and Fatigue‐Strength Distributions
Authors: Liu Peng , Hong Yili , Escobar Luis A. , Meeker William Q.
Published: December 2024

Fatigue data arise in many research and applied areas, and there have been statistical methods developed to model and analyze such data. The distributions of fatigue life and fatigue strength are often of interest to engineers designing products that might fail due to fatigue from cyclic‐stress loading. Based on a specified statistical model and the maximum likelihood method, the cumulative distribution function (cdf) and quantile function (qf) can be estimated for the fatigue‐life and fatigue‐strength distributions. Likelihood‐based confidence bands can then be obtained for the cdf and qf. This paper provides equivalence results for confidence bands for fatigue‐life and fatigue‐strength models. These results are useful for data analysis and computing implementation. We show (a) the equivalence of the confidence bands for the fatigue‐life cdf and the fatigue‐life qf, (b) the equivalence of confidence bands for the fatigue‐strength cdf and the fatigue‐strength qf, and (c) the equivalence of confidence bands for the fatigue‐life qf and the fatigue‐strength qf. Then we illustrate the usefulness of those equivalence results with two examples using experimental fatigue data.
Impact of flocculated and softened particles on UV254 inactivation of indigenous spores
Authors: Straathof Judith , Bohrerova Zuzana , Hull Natalie M.
Published: December 2024

US regulatory ultraviolet (UV) disinfection credit is typically granted when turbidity is ≤1 NTU. However, studies show turbidity does not always correlate well with UV dose responses. This study examined the impact of worst‐case high turbidity scenarios at drinking water treatment plants on UV254 inactivation of indigenous spores from unfiltered source water and unsettled flocculation and softening steps. Flocculated water (turbidity = 6.49–164 NTU) had the lowest dose response with a significantly lower Geeraerd‐tail maximum inactivation rate (kmax = 0.021 cm2/mJ) and higher residual population density (Nres = 7.081 SFU/mL). Raw source water (kmax = 0.027 cm2/mJ, Nres = 1.168 SFU/mL, turbidity = 0.978–215 NTU) and softened water (kmax = 0.030 cm2/mJ, Nres = 0.216 SFU/mL, turbidity = 318–495 NTU) had similar dose responses despite significantly different water quality. Particle size and the degree of particle‐associated spores best explained the differences in dose responses. Almost all spores were associated with flocculated particles instead of free‐floating, which increased tailing and negatively impacted UV inactivation. Based on regulatory reduction equivalent dose bias factors and UV sensitivities of spiked Bacillus subtilis spores, Cryptosporidium would be 4‐log inactivated in these raw, flocculated, or softened waters if UV transmission were ≥65%, 90%, or 80%, respectively, even though turbidity was grossly >1 NTU. Depending on particle characteristics, partial inactivation credit when turbidity is >1 NTU should be considered to avoid high‐tier violations while still protecting public health.
Electrodeposition‐Potential Tuning Rejuvenates the Concurrent Preparation from α‐Co(OH)2 with Larger Interlayer‐Spacings to β‐Co(OH)2
Authors: Wu Xiangyu , Liu Meiqi , Jiang Zhou , Li Jingjuan , Song Kexin , Wei Aofei , Meng Detian , Dong Taowen , Gao Zhenhai , Zhang Wei , Zheng Weitao
Published: December 2024

Electrodeposition is a popular method for preparing α‐Co(OH)2 as an electrode material for electrochemical energy storage. However, the preparation of technically important β‐Co(OH)2 through electrodeposition remains lacking thus far. Herein, we successfully prepared Co(OH)2 in two phases, α‐ and β‐Co(OH)2, by simply adjusting the electrodeposition potentials, as evidenced by a package of microcopy and spectroscopy analysis. Benefited from a delicate embedding and sectioning technique that may inhibit the loss of interlayer water in microscopy analysis, we find the presence of Co tetrahedron in the interlayer of α‐Co(OH)2 results in a large interlayer spacing of 7.2 Å for the crystal plane (003) compared to β‐Co(OH)2, as well as a higher chemical valence of cobalt in electrodeposited β‐Co(OH)2. The large interlayer spacing creates wider ion channels and more active storage sites for effective energy storage. Consequently, the α‐Co(OH)2 electrode exhibits more competitive electrochemical performance compared to its β counterpart.
Engineering Current Collector with 2D TiO2 Nanosheets for Stable Lithium Metal Batteries
Authors: Park Jun Seo , Nasir Mohammad , Kim Donghyoung , Jeong Hyung Mo , Park Hee Jung
Published: December 2024

The formation of lithium dendrites, driven by the non‐uniform deposition of lithium, remains a critical challenge for the performance and safety of lithium metal batteries. To address this issue, we engineer the surface of copper current collectors by depositing ultra‐thin 2D TiO2 nanosheets with varying thicknesses (0–1200 nm) as a protective layer. Half‐cells without the 2D TiO2 coating exhibit a significant decline in Coulombic efficiency after only 65 charge‐discharge cycles. In contrast, the modified current collector with the smoothest surface achieves remarkable cycling stability, maintaining ~97.6 % Coulombic efficiency after 200 cycles. Full cells incorporating these nanosheets demonstrate a good discharge capacity of ~134 mAh/g after 150 cycles at a 1 C rate. The improved electrochemical performance is attributed to the high lithium affinity and reduced surface roughness of the current collector facilitated by the 2D TiO2 buffer layer. These findings emphasize the crucial role of 2D TiO2 nanosheets in regulating Li‐ion deposition, thereby significantly improving the cycling stability and performance of lithium metal batteries.
Ru‐Based Catalysts Deposited by Atomic Layer Deposition for Non‐Alkaline Zn‐Air Batteries
Authors: Ohayon Amit , Girshevitz Olga , Ejgenberg Michal , Radovsky Gal , Noked Malachi , Kapaev Roman R.
Published: December 2024

Rechargeable zinc‐air batteries (ZAB) are a promising energy storage solution due to their low cost, low toxicity and high theoretical energy density. However, conventional alkaline ZABs face challenges such as CO₂ absorption, zinc corrosion, and poor cycle stability. To address these issues, non‐alkaline near‐neutral electrolytes offer potential benefits, but they also present slower kinetics, especially during the oxygen evolution reaction (OER) at the cell charge. This study investigates the use of atomic layer deposition (ALD) to introduce Ru‐based Nano‐sites onto carbon cathodes to enhance catalytic activity in non‐alkaline ZABs. The catalytic performance of these ALD‐treated materials was evaluated in ZABs with 1 M Zn(OAc)₂ and 1 M ZnSO₄ electrolytes. ALD‐treated Ru catalysts significantly lower the OER overpotentials, improving charging capacity and stability of the battery compared to pristine carbon and benchmark RuO2/C samples with a similar content of ruthenium. We also find that with the Ru‐based catalyst, OER proceeds exclusively through the four‐electron pathway, in contrast to a mixture of two‐ and four‐electron mechanisms observed for the pristine carbon. Our findings show, using a model catalytical system, that non‐alkaline based ZABs can be realized through cathode engineering, and that the reaction mechanism on the cathode is highly dependent on its catalytic properties.
Lactobacillus reuteri Assists Engineered Bacteria That Target Tumors to Release PD‐L1nb to Mitigate the Adverse Effects of Breast Cancer Immunotherapy
Authors: Yue Lijun , Geng Feng , Jin Jiayi , Li Wenzhen , Liu Ben , Du Maoru , Gao Xue , Lü Junhong , Pan Xiaohong
Published: December 2024

Programmed death protein‐ligand 1 (PD‐L1) inhibitors demonstrate significant antitumor efficacy by modulating T‐cell activity and inhibiting the PD‐1/PD‐L1 pathway, thus enhancing immune responses. Despite their robust effects, systemic administration of these inhibitors is linked to severe immune toxicity. To address this issue, we engineered a strain, REP, which releases PD‐L1 nanoantibodies (PD‐L1nb) to treat breast cancer and attenuate immunotherapy‐related side effects. REP selectively targets tumors and periodically releases PD‐L1nb within tumors via a quorum‐sensing lysis system. Administration of 108 colony‐forming units (CFU) of REP led to a substantial 52% reduction in tumor growth, achieved through the sustained release of PD‐L1nb. Importantly, there were no detectable lesions in other organs, with the exception of mild intestinal damage. Further, we explored the potential of a combined treatment using Lactobacillus reuteri (LR) and REP to alleviate intestinal inflammation. LR modulates the expression of inflammatory markers IL‐1β, IL‐6, and IL‐10 through the JNK pathway, reducing intestinal inflammation without compromising REP's antitumor efficacy. Consequently, we formulated a dual strategy employing an engineered strain and probiotics to reduce the adverse effects of immunotherapy in cancer treatment.
Causal Relationship Between the Abuse of Cholesterol‐Lowering Medication, Blood Pressure Medication, Insulin, and Exogenous Hormones and Cerebral Infarction
Authors: Liu Jing , Lv Dongsheng , Li Shiduo , An Zhansen , He Zefeng , Liu Yingzi
Published: December 2024

Background

Cholesterol‐lowering medications, blood pressure medication, insulin, and exogenous hormones (including hormone replacement therapy, oral contraceptives, and minipills) are commonly utilized in clinical practice. Recent studies indicate that the use of these medications may significantly influence the occurrence and progression of cerebral infarction. This study aims to investigate the relationship between these medications and cerebral infarction using Mendelian randomization (MR) analysis, with the goal of offering valuable insights for the clinical management of cerebral infarction.

Methods:

To explore the correlation between cholesterol‐lowering medication, blood pressure medication, insulin, exogenous hormones, and cerebral infarction, relevant single nucleotide polymorphisms (SNPs) were extracted from the genome‐wide association study (GWAS) database. Methods for univariate MR analysis include inverse variance weighting (IVW), the weighted median method, and the MR‐Egger method, with IVW being the predominant approach. Subsequently, multivariable Mendelian randomization (MVMR) was conducted on the positive results obtained from the IVW analysis to verify the independent effect of each positive exposure, with IVW still predominating. The causal relationship between this class of drugs and cerebral infarction was evaluated using odds ratio (OR) and 95% confidence interval (CI). MR‐PRESSO was used to test for pleiotropy. The robustness of the findings was assessed through leave‐one‐out analysis, Cochran's Q test, and funnel plot.

Results:

Univariate MR results indicated that the use of blood pressure medication, insulin, and cholesterol‐lowering medication was significantly associated with the occurrence of cerebral infarction (all p < 0.05). However, due to the stringent inclusion criteria for SNPs, the number of available SNPs is insufficient to elucidate the association between exogenous hormone drugs, contraceptives, and cerebral infarction. Furthermore, the MVMR analysis, which builds upon univariate MR, only identified significant causal associations between blood pressure medication, insulin, and cerebral infarction (p < 0.05). The association between cholesterol‐lowering medication and cerebral infarction was confounded by other positive exposures and did not demonstrate a significant causal relationship when only its independent effects were considered. After integrating the findings from both univariate and MVMR and controlling for confounding variables to the greatest extent possible, the available evidence supports only a potential causal relationship between blood pressure medication, insulin, and cerebral infarction.

Conclusion:

This study suggests that the misuse of blood pressure medications and insulin is a risk factor for the occurrence and progression of cerebral infarction.
Relationship of Neutrophil Percentage‐to‐Albumin Ratio With Stroke: Evidence From NHANES 1999–2020
Authors: Xu Shuying , Sun Yiyan , Zhang Siyao , Peng Yongjun , Dai Dechun , Zhao Leiyong
Published: December 2024

Objective

The objective of this research is to examine the association between neutrophil percentage‐to‐albumin ratio (NPAR) and stroke, providing a reference for the prevention and prognosis of clinical stroke.

Method

The study included 56,566 participants from the National Health and Nutrition Examination Survey (NHANES) to explore the association between NPAR and stroke using logistic regression and restricted cubic splines. Upon identifying the nonlinear relationship, inflection points were calculated using recursive algorithms and two‐stage linear regression models. Stratified analyses and interaction tests examined variations across population groups.

Results

After adjusting for confounders, NPAR was positively associated with stroke (OR: 1.09, 95% CI: 1.05–1.12). Restricted cubic spline analysis indicated a nonlinear trend. Beyond the inflection point, the increasing trend of stroke incidence with higher NPAR levels began to slow down. This relationship remained nonlinear in males but was linear in females.

Conclusion

This study revealed a nonlinear positive association between NPAR and stroke, with higher NPAR increasing the risk of stroke.
Comparative Efficacy of Neurofeedback Interventions for Attention‐Deficit/Hyperactivity Disorder in Children: A Network Meta‐Analysis
Authors: Wu Gang , He Qiang , Li Da , Zhang Zhang , Miao Jinli , Shu Yanping
Published: December 2024

Objective

This study aimed to synthesize and encapsulate findings from recent research (May 1, 2018 to August 1, 2023) on neurofeedback interventions for children diagnosed with attention deficit hyperactivity disorder (ADHD).

Methods

A comprehensive search was conducted across major databases and platforms, including randomized controlled trials s focusing on children aged 5–11 years with ADHD. The inclusion was broad, not restricted by ADHD subtype, gender, IQ, socioeconomic status, or coexisting conditions.

Results

From the study screening process, 13 studies were included in the network meta‐analysis, involving 1370 children. Most neurofeedback therapies surpassed placebo in ADHD symptoms. In the acceptability outcome, five neurofeedback therapies (HEG, SCP training, TBR training, SMR training, and active control) outperformed the inactive control, physical activity, and EMG therapies.

Conclusions

The potential efficacy of nonpharmacological interventions in ADHD management among children is illuminated. The findings advocate for a holistic, child‐centered approach, emphasizing the need for further in‐depth research to understand and refine these interventions.
Tracing the Reverse Relationship Among Environmental Benefits, Business Model Innovation, and Eco‐Innovation: Does Cooperation Matter?
Authors: Prokop Viktor , Carraresi Laura , Karman Agnieszka , Rehman Fazal Ur , Ibl Martin
Published: December 2024

This study investigates the direct and reverse relationships among environmental benefits, eco‐innovation, and business model innovation (BMI), emphasizing the role of national and foreign cooperation among firms. We employed a structural equation model using data from the 2014 European Community Innovation Survey (CIS), the most recent survey to include questions on firms' environmental activities and eco‐innovations. We studied 6827 firms from the Czech Republic (2363), Germany (3264), and Greece (1200). Findings confirm reverse relationships between eco‐innovation and BMI and between eco‐innovation and environmental benefits. This study challenges the notion that (foreign) cooperation positively impacts eco‐innovation, highlighting a paradox that warrants further investigation. Additionally, we emphasize the reliance of companies on cooperative partners for BMI. Our results underscore the need for a holistic approach to eco‐innovation in light of increasing global environmental challenges. Practical implications include heightened environmental awareness, adjustments to corporate business models, and enhanced cooperation within the analyzed countries.
The Development of Legal Rights for Intersex Persons: Part I: The Diversity of Intersex Conditions
Authors: Felthous Alan R. , Kahlon Chanchal
Published: December 2024

As the nature of transgender condition becomes better understood and the legal rights of transgender individuals are defined through court decisions and legislation, intersexuality ought not be overlooked. Potential commonalities as well as differences between intersexual and transgender individuals, clinically and psychosexually, may be mutually informing and relevant to their legal rights in ways that could implicate mental health services. In this review, the concepts of intersexuality and Disorders of Sexual Development are defined followed by a brief synopsis of the evolution of ancient conception of hermaphroditism into the vastly heterogenous biological conditions of today referred to as DSDs. A growing corpus of scholarly literature today argues that intersex persons should be regarded as having diverse sexual characteristics and as not disordered. Nonetheless, various conditions require understanding if the intersex person is to make informed decisions and if health providers are to recognize those conditions that constitute medical emergencies. This review and analysis compares intersex with transgender persons and provides current clinical and scientific knowledge as essential background for Part II, our following article on the advancement of legal rights of intersex persons.
Mechanism of Ligusticum wallichii—Borneol in the Treatment of Cerebral Ischemic Stroke in Rats Based On Network Pharmacology, Molecular Docking, and Experimental Verification
Authors: He Pengfen , Wang Zhifeng , Yang Jiao , Pan Pan , Shi Ting , Xu Shuangfeng , Lan Junfeng , Hao Zhihui , Yang Aiming , Chen Liang , Xi Yujiang , Wang Jian
Published: December 2024

The pharmacodynamics, molecular biology, network pharmacology, and molecular docking mechanisms of the Ligusticum wallichii and borneol medication pair (CXBP) were investigated for ischemic stroke treatment. Effective chemical components and targets of CXBP were identified using TCMSP, ETCM, and SymMap databases, whereas ischemic stroke targets were sourced from OMIM, GeneCards, TTD, PubMed, Web of Science, CNKI, Wanfang Data, and VIP databases. Protein–protein interaction (PPI) networks were generated using the STRING database, and GO and KEGG enrichment analyses were conducted using Metascape. A “disease–pathway–target–component–drug” network was created in Cytoscape, and molecular docking was confirmed with PyMOL and AutoDock tools. Rat models of MCAO were established to evaluate neurological scores, triphenyltetrazolium chloride (TTC) staining, and Nissl staining. Key components were validated through enzyme‐linked immunosorbent assay (ELISA), real‐time polymerase chain reaction (PCR), and immunohistochemistry. Thirty‐three active ingredients and 419 potential targets for CXBP, with key compounds including Z‐6,8′,7,3′‐diligustilide, cedrene, (+)‐alpha‐funebrene, POL, dipterocarpol, oleanolic acid, 1‐acetyl‐beta‐carboline, and erythrodiol. Critical targets included ESR1, PRKCA, and PTPN6. KEGG pathway analysis revealed 179 signaling pathways, primarily neuroactive ligand–receptor interactions, whereas GO enrichment analysis identified 2911 biological processes, 398 molecular activities, and 203 cellular components. The neurological function scores and TTC staining of the infarcted brain regions were significantly improved following CXBP intervention compared to the MCAO group. These findings were supported by Nissl staining, which demonstrated better preserved cellular morphology and a significantly higher number of Nissl vesicles in the CXBP group. ELISA analysis revealed substantial modulation in gene expression: levels of PRKCA, PTPN6, ESR1, and TNF‐α changed significantly, whereas IL‐1β, IL‐6, and TNF‐α were notably downregulated compared to the MCAO group. PCR results corroborated these findings, showing a significant decrease in PRKCA expression and marked downregulation of IL‐1β, IL‐6, and TNF‐α, whereas ESR1 and PTPN6 levels increased significantly. Immunohistochemical analysis further confirmed these results, with the CXBP and nimodipine groups exhibiting higher ESR1 and PTPN6 expression and lower PRKCA expression compared to the MCAO group. To improve cerebral ischemia and reperfusion injury, CXBP improves ischemic stroke outcomes through key active ingredients (e.g., Z‐6,8′,7,3′‐diligustilide, cedrene, and oleanolic acid) and targets ESR1, PRKCA, and PTPN6, modulating multiple signaling pathways to alleviate cerebral ischemia–reperfusion injury.
Two New α‐Glucosidase Inhibitors from Haplophyllum tuberculatum: Inhibition Kinetics and Mechanistic Insights Through in Vitro and in Silico Approaches
Authors: Shah Muddaser , Ullah Saeed , Halim Sobia Ahsan , Khan Ajmal , Gibbons Simon , Csuk René , Murad Waheed , Rehman Najeeb Ur , Al‐Harrasi Ahmed
Published: December 2024

Diabetes is a multifactorial global health disorder marked by unusually high plasma glucose levels, which can lead to serious consequences including diabetic neuropathy, kidney damage, retinopathy, and cardiovascular disease. One effective therapy approach for reducing hyperglycemia associated with type 2 diabetes is to target α‐glucosidase, enzymes that catalyze starch breakdown in the intestine. In the current study, two new (1, 2) and nine known (3–11) compounds were isolated from the rutaceous plant Haplophyllum tuberculatum and characterized by extensive nuclear magnetic resonance spectroscopic techniques and high‐resolution electrospray ionization mass spectrometry. After structural elucidation, nine compounds were evaluated for their ability to inhibit α‐glucosidase, a target for the treatment of type‐2 diabetes. Among them, three compounds (7, 5, and 2) exhibited notable inhibition with half‐maximal inhibitory concentration (IC50) values of 3.42 ± 0.12, 5.79 ± 0.28, and 6.75 ± 1.18 µM, respectively, while the remaining six compounds (1, 3, 4, 6, 8, and 9) had a moderate activity with IC50 values ranging from 12.14 ± 0.35 to 24.60 ± 0.57 µM, compared to the standard drug acarbose (IC50 = 875.75 ± 1.24 µM). A kinetic study of compounds 5 and 7 exhibited the competitive type of inhibition with Ki values of 4.82 ± 0.0036 and 3.92 ± 0.0062 µM, respectively. Furthermore, a structure‐based prediction of the compounds’ binding mode suggested that these inhibitors fitted exceptionally well within the active site of the target enzyme, α‐glucosidase, forming multiple hydrogen and hydrophobic interactions with its active site residues. In conclusion, compounds with potent α‐glucosidase inhibitory activity are abundant in nature and can be explored and further developed for treating diabetes mellitus.
Phytochemical Characterization, Prooxidant, Antiproliferative and Anti‐Inflammatory Potential of Meyna spinosa Roxb. Ex Link Ripe Fruit
Authors: Boruah Jyoti Lakshmi Hati , Gogoi Moloya , Famhawite Vanlalhruaii , Barman Dipankar , Das Deep Jyoti , Puro K Nusalu , Biswas Anupam , Mridha Prosenjit , Gogoi Parishmita , Gajbhiye Rahul , Baishya Rinku
Published: December 2024

This study highlights the prooxidant, antiproliferative and anti‐inflammatory potential of ripe Meyna spinosa Roxb. Ex Link fruit extracts. Chemical analysis by high‐resolution mass spectrometry and AAS identified compounds like ursolic acid, oleanolic acid, lupeol, betulin, scopoletin, phloroglucinol and secoxyloganin and micro‐elements like iron, copper, zinc and manganese. Antioxidant assays (DPPH, FRAP, metal chelation, reaction oxygen species) revealed that the M. spinosa ethyl acetate extract (MSEA) had higher phenolic (37.83 mg GAE/g DW) and flavonoid (60.22 mg QE/g DW) content, showing strong antioxidant activity (IC50 of 7.5 µg/mL), while the M. spinosa methanolic extract (MSM) exhibited higher FRAP activity (39.666 µg AAE/g DW). Prooxidant activity was demonstrated through Trolox and NADH oxidation. Both extracts exhibited antiproliferative effects in A549 and MCF7 cancer cells with an increase in concentration and time. Anti‐inflammatory effects were observed by reductions in nitric oxide, COX‐2, IL‐6 and TNF‐α levels in lipopolysaccharides‐stimulated RAW 264.7 and THP‐1 cells. Nitrite levels reduced from 23.778 to 5.222 µM, COX‐2 levels from 51.136 to 9.581 µg/mL, IL‐6 levels from 62.728 ng/mL to 13.463 pg/mL and TNF‐α level from 474.890 to 143.115 pg/mL. In vivo, MSEA reduced carrageenan‐induced paw oedema by 23.45%.
Microorganism‐Derived Bisindole Alkaloids With Anticancer Potential and Their Mechanisms: A Comprehensive Review
Authors: Zhang Zi‐Long , Xu Hao‐Nan , Gong Chuan‐Ming , Li Yu‐Ze , Song Xiao‐Mei , Li Yi‐Ming , Zhang Dong‐Dong , Wang Rui
Published: December 2024

Bisindole alkaloids constitute a significant class of natural compounds distinguished by their characteristic bisindole structure and renowned for their anticancer properties. Over the last six decades, researchers have isolated 425 microorganism‐derived bisindole alkaloids (MDBAs). Among them, 187 MDBAs have demonstrated anticancer properties against various in vitro cancer cell lines, primarily by impeding the cell cycle, restraining cell proliferation, and inducing apoptosis and autophagy. These effects are mediated by regulating key targets and signaling pathways such as hypoxia‐inducible factor (HIF)‐1, MAPK, and phosphatidylinositol 3‐kinase (PI3K)/AKT/mTOR. This review provides a comprehensive examination of the sources, chemical diversity, and anticancer properties of these compounds. Furthermore, it summarizes the structure–activity relationship (SAR), druggability, and the mechanisms underlying MDBAs’ anticancer effects. Ultimately, this article aims to furnish a thorough overview of the advancements in the investigation of microorganism‐derived bisindole alkaloids for their continued development and utilization.
Inhibition of Oral Biofilms and Enhancement of Anticancer Activity on Oral Squamous Carcinoma Cells Using Caffeine‐Coated Titanium Oxide Nanoparticles
Authors: Hussain Shaik Althaf , Ramasamy Mohankumar , Shaik Mohammed Rafi , Shaik Baji , Deepak Paramasivam , Thiyagarajulu Nathiya , Matharasi Antonyraj Anahas Perianaika , Guru Ajay
Published: December 2024

The fungus Candida albicans is a prominent cariogenic fungal agent that works in association with Streptococcus mutans to accelerate the formation of oral cancer and tooth decay. This study evaluates caffeine‐encapsulated titanium oxide nanoparticles (CF‐TiO2 NPs) for their potential to prevent biofilm formation on teeth and enhance oral anticancer treatment by influencing apoptotic gene regulation. The synthesized CF‐TiO2 NPs were characterized using ultraviolet, scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, and Fourier‐transform infrared spectroscopy analyses, and their antioxidant activity was confirmed through free radical quenching studies. Antimicrobial efficacy was assessed using a zone of inhibition test, revealing strong activity against dental pathogens with a minimal inhibitory concentration of 80 µg/mL. Molecular docking using AutoDock explored interactions between CF and biofilm target sites, supporting their inhibitory potential. In vitro cytotoxicity studies on KB cancer cells showed a dose‐dependent increase in cytotoxic effects, with CF‐TiO2 NPs promoting apoptotic gene upregulation at concentrations of 20–160 µg/mL. CF‐TiO2 NPs demonstrated excellent antioxidant, antibacterial, and anticancer properties, showcasing their promise for oral therapeutic applications. This research highlights a novel approach to managing oral infections and associated complications while improving systemic oral health. Notably, this study is the first to report the biofilm‐inhibitory and anticancer potential of CF‐TiO2 NPs.
Essential Oil From Tetrapanax papyrifer (Hook.) K. Koch: Chemical Composition, Antioxidant Activity, α‐Glucosidase Inhibitory Effect Integrating Molecular Docking Analysis
Authors: Xu Ziyue , Zhu Jiadong , Gao Peizhong , Zhu Xinyu , Zhang Yusen , Liu Xu
Published: December 2024

This study investigated the chemical composition of essential oil from Tetrapanax papyrifer and evaluated its antioxidant and anti‐α‐glucosidase activity. A total of 61 essential oil compounds from T. papyrifer were identified by gas chromatography‐mass spectrometry (GC‐MS) and gas chromatography‐flame ionization detector (GC‐FID). The essential oil is rich in sesquiterpenoids (96.05%), with major components identified as β‐cubebene (13.96%), caryophyllene (13.43%), α‐cubebene (12.12%), copaene (7.89%), δ‐cadinene (7.29%), eremophilene (6.15%), humulene (5.26%). The essential oil showed dose‐dependent antioxidant activity with IC50 values of 723.15 ± 24.10 and 200.74 ± 9.90 µg/mL for 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and 2,2'‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) assays, respectively. Ferric reducing antioxidant power (FRAP) antioxidant capacity was 222.73 ± 25.49 µmol/g. The essential oil exhibited a 17.86% ± 0.56% inhibitory effect against α‐glucosidase at 500 µg/mL. Moreover, in silico molecular docking analyses were utilized to validate the in vitro anti‐α‐glucosidase results further.
Novel Aminothiazole–Chalcone Analogs: Synthesis, Evaluation Acetylcholinesterase Activity, In Silico Analysis
Authors: Keçeci Sarıkaya Meryem , Yıldırım Şuheda , Kocyigit Umit M. , Ceylan Mustafa , Yırtıcı Ümit , Eyüpoğlu Volkan
Published: December 2024

In this study, novel thiazole–chalcone analogs were synthesized, and their inhibitory effects on acetylcholinesterase (AChE) were examined. In vitro enzyme activity studies were conducted to calculate IC50 values, which were found to range between 2.55 and 72.78 µM (tacrine IC50 = 53.31 µM). The Ki values of the compounds showing the best inhibition (6g and 6e) were calculated and compared to those of the standard substance tacrine. All compounds reduced the AChE activity. Additionally, predictions made with SwissADME indicated that all compounds complied with Lipinski's rules and possessed good oral bioavailability properties, and the inhibitory effects of compounds 6e and 6g on AChE were evaluated using molecular docking and molecular dynamics simulations (100 ns). The results showed that compounds 6e and 6g had strong and stable interactions with AChE.
Magnolol as an Antibacterial Agent Against Drug‐resistant Bacteria Targeting Filamentous Temperature‐sensitive Mutant Z
Authors: Sun Ning , Deng Xin , Kong Hanqin , Zhi Ziling , Jiang Guli , Xiong Jing , Chen Sisi , Li Song , Yuan Wenchang , Wong Wing‐Leung
Published: December 2024

The emergence of multiple drug‐resistant bacteria poses critical health threats worldwide. It is urgently needed to develop potent and safe antibacterial agents with novel bactericidal mechanisms to treat these infections. In this study, magnolol was identified as a potential bacterial cell division inhibitor by a cell‐based screening approach. This compound showed good antibacterial activity against a number of Gram‐positive pathogens (minimum inhibitory concentration 8–16 µg/mL) including methicillin‐resistant Staphylococcus aureus and vancomycin‐resistant Enterococcus. Further results obtained from biochemical experiments demonstrated that magnolol could markedly disrupt GTPase activity and filamentous temperature‐sensitive mutant Z (FtsZ) polymerization, consistent with the impediment to cell division in the bacteria tested. The in vivo antibacterial activity of magnolol was evaluated with a Galleria mellonella larvae model. The results showed that magnolol significantly increased the survival rate of larvae infected with methicillin‐resistant S. aureus. The interaction pattern of magnolol with FtsZ was investigated through molecular docking. The finding may offer meaningful insights into the mechanism of action of the compound. The results point to magnolol as a promising antimicrobial compound that inhibits cell division by affecting FtsZ polymerization and has the potential to be developed into an effective antimicrobial drug by further structure modification.