bluuebunny/crossref_metadata_2025 huggingface dataset:
Akt activator SC79 stimulates antibacterial nitric oxide generation in human nasal epithelial cells in vitro
Authors: Lee Robert J. , Adappa Nithin D. , Palmer James N.
Published: January 2024

Background

The role of Akt in nasal immunity is unstudied. Akt phosphorylates and activates endothelial nitric oxide synthase (eNOS) expressed in epithelial ciliated cells. Nitric oxide (NO) production by ciliated cells can have antibacterial and antiviral effects. Increasing nasal NO may be a useful antipathogen strategy in chronic rhinosinusitis (CRS). We previously showed that small‐molecule Akt activator SC79 induces nasal cell NO production and suppresses IL‐8 via the transcription factor Nrf‐2. We hypothesized that SC79 NO production may additionally have antibacterial effects.

Methods

NO production was measured using fluorescent dye DAF‐FM. We tested effects of SC79 during co‐culture ofPseudomonas aeruginosawith primary nasal epithelial cells, using CFU counting and live–dead staining to quantify bacterial killing. Pharmacology determined the mechanism of SC79‐induced NO production and tested dependence on Akt.

Results

SC79 induced dose‐dependent, Akt‐dependent NO production in nasal epithelial cells. The NO production required eNOS and Akt. The NO released into the airway surface liquid killedP. aeruginosa. No toxicity (LDH release) or inflammatory effects (IL8 transcription) were observed over 24 h.

Conclusions

Together, these data suggest multiple immune pathways are stimulated by SC79, with antipathogen effects. This in vitro pilot study suggests that a small‐molecule Akt activator may have clinical utility in CRS or respiratory other infection settings, warranting future in vivo studies.
Bidirectional Regulation of Intracellular Enzyme Activity Using Light‐Driven Nano‐Inhibitors
Authors: Zhao Yu , Huang Qingqing , Li Qiushi , Chen Zihan , Liu Yang
Published: January 2024

Photochemical regulation provides precise control over enzyme activities with high spatiotemporal resolution. A promising approach involves anchoring “photoswitches” at enzyme active sites to modulate substrate recognition. However, current methods often require genetic mutations and irreversible enzyme modifications for the site‐specific anchoring of “photoswitches”, potentially compromising the enzyme activities. Herein, we present a pioneering reversible nano‐inhibitor based on molecular imprinting technique for bidirectional regulation of intracellular enzyme activity. The nano‐inhibitor employs a molecularly imprinted polymer nanoparticle as its body and azobenzene‐modified inhibitors (“photoswitches”) as the arms. By using a target enzyme as the molecular template, the nano‐inhibitor acquires oriented binding sites on its surface, resulting in a high affinity for the target enzyme and non‐covalently firm anchoring of the azobenzene‐modified inhibitor to the enzyme active site. Harnessing the reversible isomerization of azobenzene units upon exposure to ultraviolet and visible light, the nano‐inhibitor achieves bidirectional enzyme activity regulation by precisely docking and undocking inhibitor at the active site. Notably, this innovative approach enables the facile in situ regulation of intracellular endogenous enzymes, such as carbonic anhydrase. Our results represent a practical and versatile tool for precise enzyme activity regulation in complex intracellular environments.
A Giant Heterometallic Polyoxometalate Nanocluster for Enhanced Brain‐Targeted Glioma Therapy
Authors: Song Nizi , Lu Mengya , Liu Jiancai , Lin Ming , Shangguan Ping , Wang Jiefei , Shi Bingyang , Zhao Junwei
Published: January 2024

Giant heterometallic polyoxometalate (POM) clusters with precise atom structures, flexibly adjustable and abundant active sites are promising for constructing functional nanodrugs. However, current POM drugs are almost vacant in orthotopic brain tumor therapy due to the inability to effectively penetrate the blood–brain barrier (BBB) and low drug activity. Here, we designed the largest (3.0 nm × 6.0 nm) transition‐metal–lanthanide co‐encapsulated POM cluster {[Ce10Ag6(DMEA)(H2O)27W22O70][B‐α‐TeW9O33]9}288− featuring 238 metal centers via synergistic coordination between two geometry‐unrestricted Ce3+ and Ag+ linkers with tungsten‐oxo cluster fragments. This POM was combined with brain‐targeted peptide to prepare a brain‐targeted nanodrug that could efficiently traverse BBB and target glioma cells. The Ag+ active centers in the nanodrug specifically activate reactive oxygen species to regulate the apoptosis pathway of glioma cells with a low half‐maximal inhibitory concentration (5.66 μM). As the first brain‐targeted POM drug, it efficiently prolongs the survival of orthotopic glioma‐bearing mice.
Patient‐derived Immunocompetent Tumor Organoids: A Platform for Chemotherapy Evaluation in the Context of T‐cell Recognition**
Authors: Zhao Zihan , Zhang Shuren , Jiang Ning , Zhu Wenjie , Song Dongfan , Liu Siyang , Yu Wenhao , Bai Yuhao , Zhang Yulin , Wang Xiaoyu , Zhong Xuanmeng , Guo Hongqian , Guo Zijian , Yang Rong , Li Jie P.
Published: January 2024

Most of the anticancer compounds synthesized by chemists are primarily evaluated for their direct cytotoxic effects at the cellular level, often overlooking the critical role of the immune system. In this study, we developed a patient‐derived, T‐cell‐retaining tumor organoid model that allows us to evaluate the anticancer efficacy of chemical drugs under the synergistic paradigm of antigen‐specific T‐cell‐dependent killing, which may reveal the missed drug hits in the simple cytotoxic assay. We evaluated clinically approved platinum (Pt) drugs and a custom library of twenty‐eight PtIV compounds. We observed low direct cytotoxicity of Pt drugs, but variable synergistic effects in combination with immune checkpoint inhibitors (ICIs). In contrast, the majority of PtIV compounds exhibited potent tumor‐killing capabilities. Interestingly, several PtIV compounds went beyond direct tumor killing and showed significant immunosynergistic effects with ICIs, outstanding at sub‐micromolar concentrations. Among these, Pt‐19, PtIV compounds with cinnamate axial ligands, emerged as the most therapeutically potent, demonstrating pronounced immunosynergistic effects by promoting the release of cytotoxic cytokines, activating immune‐related pathways and enhancing T cell receptor (TCR) clonal expansion. Overall, this initiative marks the first use of patient‐derived immunocompetent tumor organoids to explore and study chemotherapy, advancing their path toward more effective small molecule drug discovery.
N‐Heterocycle‐Editing to Access Fused‐BN‐Heterocycles via Ring‐Opening/C−H Borylation/Reductive C−B Bond Formation
Authors: Zhang Xu , Su Wanlan , Guo Huosheng , Fang Pengyuan , Yang Kai , Song Qiuling
Published: January 2024

Skeletal editing of N‐heterocycles has recently received considerable attention, and the introduction of boron atom into heterocycles often results in positive property changes. However, direct enlargement of N‐heterocycles through boron atom insertion is rarely reported in the literature. Here, we report a N‐heterocyclic editing reaction through the combination boron atom insertion and C−H borylation, accessing the fused‐BN‐heterocycles. The synthetic potential of this chemistry was demonstrated by substrate scope and late‐stage diversification of products.
Confining Bismuth‐Halide Perovskite in Mesochannels of Silica Nanomembranes for Exceptional Photocatalytic Abatement of Air Pollutants
Authors: Yang Jingling , Liu Bin , Zeng Lixi , Du Bibai , Zhou Yingtang , Tao Hengcong , Yun Yang , Zhu Mingshan
Published: January 2024

Spatially confined photocatalysis has emerged as a viable strategy for the intensification of various redox reactions, but the influence of confined structure on reaction behavior is always overlooked in gas‐solid reactions. Herein, we report a nanomembrane with confining Cs3Bi2Br9 nanocrystals inside vertical channels of porous insulated silica thin sheets (CBB@SBA(⊥)) for photocatalytic nitric oxide (NO) abatement. The ordered one‐dimensional (1D) pore channels with mere 70 nm channel length provide a highly accessible confined space for catalytic reactions. A record‐breaking NO conversion efficiency of 98.2 % under a weight hourly space velocity (WHSV) of 3.0×106 mL g−1 h−1, as well as exceptionally high stability over 14 h and durability over a wide humidity range (RH=15–90 %) was realized over SBA(⊥) confined Cs3Bi2Br9, well beyond its nonconfined analogue and the Cs3Bi2Br9 confine in Santa Barbara Amorphous (SBA‐15). Mechanism studies suggested that the insulated pore channels of SBA(⊥) in CBB@SBA(⊥) endow concentrated electron field and enhanced mass transfer that render high exposure of reactive species and lower reaction barrier needs for ⋅O2− formation and NO oxidation, as well as prevents structural degradation of Cs3Bi2Br9. This work expands an innovative strategy for designing efficient photocatalysts for air pollution remediation.
Learning functional human anatomy with a new interactive three‐dimensional digital tool
Authors: Gallot Mélanie , di Rienzo Franck , Binay Marion , Collet Christian , Hoyek Nady
Published: January 2024

Human anatomy requires understanding spatial relationships among anatomical structures and is often perceived as difficult to learn by students. To overcome this concern, several digital tools exist with some strengths and limitations among which the lack of interactivity especially for complex functional anatomy learning. In this way, a new interactive three‐dimensional tool called Antepulsio was designed. Antepulsio was assessed by comparing three groups of first year kinesiology students to test whether it is likely to favor functional anatomy learning during three training sessions spread over a week. The experiment was conducted during a real academic course. Laterality judgment, 3D spatial abilities and working memory abilities from all participants were previously collected to create three homogeneous groups: the active group (n = 17, 17.76 ± 0.56 years) interacted with Antepulsio, the passive group (n = 18, 17.89 ± 0.83 years) watched videos of Antepulsio while the control group (n = 15, 18.07 ± 0.80 years) performed a neutral activity unrelated to anatomy. Anatomy knowledge was also assessed during pretest, posttest, and retention test (8 weeks after the posttest). The most significant outcome of this study revealed that in case of better working visual memory, the active group outperformed the passive group between pretest and retention test (p < 0.01). In other words, Antepulsio tool is efficient only for students with high visuospatial working memory. These selective benefits of Antepulsio are discussed in terms of cognitive load, training duration and the necessary period of familiarization with the tool.
Bi‐ and tridentate coordination behaviour of a novel bis(phosphinimino)methanide ligand
Authors: Burgert Bastian B. , Sun Xiaofei , Hauser Adrian , Wingering Perrine M. R. , Breher Frank , Roesky Peter W.
Published: January 2024

Herein, we report the synthesis of a novel ferrocenyl‐functionalized bis(phosphinimino)methane ligand (CH2(PPh2NFc)2). Deprotonation of CH2(PPh2NFc)2 with KN(SiMe3)2 gave the dimeric species [K{CH(PPh2NFc)2}]2, which was further reacted with ECl2 (E=Ge, Sn) to yield the tetrylene compounds [{CH(PPh2NFc)2}ECl]. The ligand and the resulting tetrylenes were examined for their electrochemical properties with the aid of cyclic voltammetry. Furthermore, the reaction of the tetrylenes [{CH(PPh2NFc)2}ECl] with [AuC6F5(tht)] resulted in the bimetallic complexes [{(AuC6F5)CH(PPh2NFc)2}ECl] with an unusual Au coordination on the ligand backbone.
Efficiency and safety of hepatic arterial infusion chemotherapy (HAIC) combined with anti‐PD1 therapy versus HAIC monotherapy for advanced hepatocellular carcinoma: A multicenter propensity score matching analysis
Authors: Li Yangyang , Liu Wendao , Chen Junwei , Chen Yongxin , Guo Jiandong , Pang Huajin , Zhang Wentao , An Chao , Li Chengzhi
Published: January 2024

Purpose

To investigate the clinical efficacy and safety of combination therapy of hepatic arterial infusion chemotherapy (HAIC) and anti‐programmed cell death protein‐1 (PD‐1) therapy in the treatment of advanced hepatocellular carcinoma (HCC).

Methods

In this retrospective clinical research, from March 2018 to December 2019, 1158 HCC patients categorized as BCLC stage C were reviewed for eligibility. We utilized propensity score matching (PSM) to mitigate initial disparities between the groups. The evaluation of the best tumor response was conducted in accordance with mRECIST 1.1 criteria. The difference in survival outcomes including overall survival (OS), progression‐free survival (PFS), and objective response rate (ORR) between groups were compared.

Results

Following the eligibility review, 453 patients underwent a combined treatment of HAIC with PD1 inhibitors (HAIC‐PD1 group), while 221 patients received HAIC monotherapy (HAIC group) met the inclusion criteria and were finally enrolled in this study. In the entire cohort, the HAIC‐PD1 group exhibited significantly prolonged overall survival (median overall survival: 40.4 months vs. 9.7 months, p < 0.001) and progression‐free survival (median progression‐free survival: 22.1 months vs. 5.8 months, p < 0.001). By propensity score, patients were matched according to baseline differences, resulting in all 442 patients in group HAIC‐PD1 (n = 221) and group HAIC (n = 221). After PSM adjustment, as well, the survival of the HAIC‐PD1 group was still distinctly longer than the HAIC group (median overall survival time, 40.4 months vs 9.7 months, p < 0.001; median progression‐free survival, 22.1 months vs 5.7 months, p < 0.001). Univariate and multivariable analysis demonstrated that AFP level, metastasis, and therapeutic schedule were independent predictive factors for overall survival.

Conclusion

The combination therapy of HAIC and PD1 inhibitors successfully extended OS to advanced HCC patients and could be a better choice than HAIC monotherapy.
Deaths related to antipsychotics associated with higher doses
Authors: Knopf Alison
Published: January 2024

Prescribers will need to focus on dose when considering mortality and antipsychotic prescribing, according to a new study.
Left ventricular hemodynamics with veno‐arterial extracorporeal membrane oxygenation
Authors: Kalra Rajat , Alexy Tamas , Bartos Jason A. , Prisco Anthony R. , Kosmopoulos Marinos , Maharaj Valmiki R. , Bernal Alejandra Gutierrez , Elliott Andrea M. , Garcia Santiago , Raveendran Ganesh , John Ranjit , Burkhoff Daniel , Yannopoulos Demetris
Published: January 2024

Background

There is considerable debate about the hemodynamic effects of veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO).

Aims

To evaluate the changes in left ventricular (LV) function, volumes, and work in patients treated with VA‐ECMO using invasive LV catheterization and three‐dimensional echocardiographic volumes.

Methods

Patients on VA‐ECMO underwent invasive hemodynamic evaluation due to concerns regarding candidacy for decannulation. Hemodynamic parameters were reported as means±standard deviations or medians (interquartile ranges) after evaluating for normality. Paired comparisons were done to evaluate hemodynamics at the baseline (highest) and lowest tolerated levels of VA‐ECMO support.

Results

Twenty patients aged 52.3 ± 15.8 years were included. All patients received VA‐ECMO for refractory cardiogenic shock (5/20 SCAI stage D, 15/20 SCAI stage E). At 3.0 (2.0, 4.0) days after VA‐ECMO cannulation, the baseline LV ejection fraction was 20% (15%, 27%). The baseline and lowest VA‐ECMO flows were 4.0 ± 0.6 and 1.5 ± 0.6 L/min, respectively. Compared to the lowest flow, full VA‐ECMO support reduced LV end‐diastolic volume [109 ± 81 versus 134 ± 93 mL, p = 0.001], LV end‐diastolic pressure (14 ± 9 vs. 19 ± 9 mmHg, p < 0.001), LV stroke work (1858 ± 1413 vs. 2550 ± 1486 mL*mmHg, p = 0.002), and LV pressure‐volume area (PVA) (4507 ± 1910 vs. 5193 ± 2388, p = 0.03) respectively. Mean arterial pressure was stable at the highest and lowest flows (80 ± 16 vs. 75 ± 14, respectively; p = 0.08) but arterial elastance was higher at the highest VA‐ECMO flow (4.9 ± 2.2 vs lowest flow 2.7 ± 1.6; p < 0.001).

Conclusions

High flow VA‐ECMO support significantly reduced LV end‐diastolic pressure, end‐diastolic volume, stroke work, and PVA compared to minimal support. The Ea was higher and MAP was stable or minimally elevated on high flow.
Selective Glycerol‐to‐glycerate Electro‐oxidation on Cerium‐modified Pt/C Nanocatalyst in an Alkaline Direct Alcohol Fuel Cell: Cogeneration of Energy and Value‐added Products
Authors: Cursi Fabiano S. , Grimaud Laurie , Rousseau Julie , Servat Karine , Morais Cláudia , Napporn Teko W. , de Andrade Adalgisa R. , Kokoh K. Boniface
Published: January 2024

Glycerol electro‐oxidation reaction was performed in an alkaline environment with an anion exchange membrane fuel cell (AEMFC) operating in bath mode at low Pt‐loadings. BAE‐synthesized Pt/C and PtCe/C nanostructured catalysts were used as anode materials during 4‐hour operation to selectively obtain 65 % and 41 % of glycerate as main product, respectively. The modification of Pt with Ce improved the catalytic activity of the Pt/C catalyst generating 30 % more energy density after 4‐hour operation by achieving a higher degree of glycerol oxidation in cogeneration with added‐value products confirmed by spectroelectrochemical (in situ FTIR) and liquid chromatography coupled with mass spectrometry (LC–MS) analyses. The bifunctional mechanism generated by the presence of Ce is used to explain the improvement in the catalytic activity of Pt/C, due to the properties of this rare earth element to adsorb oxygenated species (OH−) and promote oxidation. The cathode material was a polyol‐synthesized PdFe/C electro‐catalyst for ORR that presented impressive stability and tolerance to glycerol.
Atomically dispersed Mn–Nx catalysts derived from Mn‐hexamine coordination frameworks for oxygen reduction reaction
Authors: Zhong Guoyu , Zou Liuyong , Chi Xiao , Meng Zhen , Chen Zehong , Li Tingzhen , Huang Yongfa , Fu Xiaobo , Liao Wenbo , Zheng Shaona , Xu Yongjun , Peng Feng , Peng Xinwen
Published: January 2024

Metal‐organic frameworks recently have been burgeoning and used as precursors to obtain various metal–nitrogen–carbon catalysts for oxygen reduction reaction (ORR). Although rarely studied, Mn–N–C is a promising catalyst for ORR due to its weak Fenton reaction activity and strong graphitization catalysis. Here, we developed a facile strategy for anchoring the atomically dispersed nitrogen‐coordinated single Mn sites on carbon nanosheets (MnNCS) from an Mn‐hexamine coordination framework. The atomically dispersed Mn–N4 sites were dispersed on ultrathin carbon nanosheets with a hierarchically porous structure. The optimized MnNCS displayed an excellent ORR performance in half‐cells (0.89 V vs. reversible hydrogen electrode (RHE) in base and 0.76 V vs. RHE in acid in half‐wave potential) and Zn–air batteries (233 mW cm−2 in peak power density), along with significantly enhanced stability. Density functional theory calculations further corroborated that the Mn–N4–C12 site has favorable adsorption of *OH as the rate‐determining step. These findings demonstrate that the metal‐hexamine coordination framework can be used as a model system for the rational design of highly active atomic metal catalysts for energy applications.
Photoinduced Puffing with Large Volume Expansion and Photomechanical Motions induced by Topochemical [4+4] Reactions in Molecular Crystal Solvates
Authors: Giri Prasenjit , Panda Atanu , Panda Manas K.
Published: January 2024

In this work, we report the first example of two crystal solvates of an anthracene‐benzhydrazide based molecule (Ant) that display very distinct photo‐responsive behaviour when 365 or 405 nm or visible light is illuminated. For the first time, the crystal hydrate that has water molecule in the lattice (hereafter named as Ant−H2O) display fascinating puffing behavior with large volume expansion upto 50 % accompanied with surface modulation when illuminated with 405 nm light, a phenomenon very much similar to the rice or popcorn puffing by thermal treatment. Utilizing the properties of photoconverted Ant−H2O crystals, we have demonstrated their application in photoinduced enhanced liquid absorption using various liquids/solutions. The other crystal solvate having DMF in the crystal lattice (hereafter named as Ant−DMF) responds to 405 nm light by bending, twisting, chopping, jumping or splitting etc. The chopping of Ant−DMF crystal was also observed under ambient/white light but at a slower rate compared to 405 nm light. Single crystal X‐ray diffraction study reveals that the photoinduced puffing and photomechanical effects of these materials are rooted to the topochemical [4+4] cycloaddition reaction between the anthracene moieties that facilitate molecular packing change assisted by the reconfiguration of intermolecular non‐covalent interactions involving lattice trapped solvent molecules.
Refined Synthesis and Single Crystal Growth of PbGa2Se4by Chemical Vapor Transport Method for Photodetection
Authors: Ji Leilei , Xiao Bao , Yin Ziang , Sun Qihao , Xu Yadong , Jie Wanqi
Published: January 2024

Ternary chalcogenide PbGa2Se4with high resistivity, photosensitivity, and excellent nonlinear properties, exhibits a potential application in optoelectronic and nonlinear optical devices. However, the preparation of large‐sized pure PbGa2Se4crystals is challenging due to the presence of peritectic reaction and a narrow homogeneity region. Here, a “quenching‐annealing” method (quenching at 850 °C in ice water, and then annealing at 650 °C for 250 h by reheating) is developed to eliminate the PbSe second phase during the synthesis. Subsequently, the PbGa2Se4single crystals are successfully grown using chemical vapor transport (CVT) with the I2as the transport agent. The resulting crystal exhibits the crystal structure belonging toFdddspace group with the lattice parameters ofa= 12.7192 Å,b= 21.2831 Å, andc= 21.5226 Å. Additionally, it possesses a wide bandgap (≈2.26 eV), high resistivity (6.59 × 1012Ω·cm), and defect density calculated via space charge limited current measurement (SCLC) as 2.46 × 1011cm−3. Photodetectors based on these as‐grown crystals demonstrate exceptional photosensitivity along with a high detectivity (3.2 × 108Jones).
Out‐group help in the time of Covid‐19 and intergroup reconciliation in the Western Balkans
Authors: Castano Emanuele , Čehajić‐Clancy Sabina , Leidner Bernhard , Baumert Anna , Li Mengyao
Published: January 2024

In March 2021, Serbia made the unprecedented announcement to offer free Covid‐19 vaccination to citizens of Bosnia and Herzegovina, and notably to Bosniaks, against whom three decades earlier Serbia had waged a bloody war. How was this policy appraised and, most importantly, did the policy appraisal impact reconciliation? We report here the results of a longitudinal investigation amid a representative sample of Bosniak youth (N = 450). Results suggest that a positive appraisal of this actual, state‐level policy, predicted improvement on a series of intergroup reconciliation indicators (e.g., trust in the out‐group, forgiveness for past violence, hope for future relationship), particularly so amid those who are strongly attached to their Bosniak in‐group.
A complete pipeline enables haplotyping and phasing macrohaplotype in long sequencing reads for polyploidy samples and a multi‐source DNA mixture
Authors: Wang Xuewen , Muenzler Melissa , King Jonathan , Liu Muyi , Li Hongmin , Budowle Bruce , Ge Jianye
Published: January 2024

Macrohaplotype combines multiple types of phased DNA variants, increasing forensic discrimination power. High‐quality long‐sequencing reads, for example, PacBio HiFi reads, provide data to detect macrohaplotypes in multiploidy and DNA mixtures. However, the bioinformatics tools for detecting macrohaplotypes are lacking. In this study, we developed a bioinformatics software, MacroHapCaller, in which targeted loci (i.e., short TRs [STRs], single nucleotide polymorphisms, and insertion and deletions) are genotyped and combined with novel algorithms to call macrohaplotypes from long reads. MacroHapCaller uses physical phasing (i.e., read‐backed phasing) to identify macrohaplotypes, and thus it can detect multi‐allelic macrohaplotypes for a given sample. MacroHapCaller was validated with data generated from our designed targeted PacBio HiFi sequencing pipeline, which sequenced ∼8‐kb amplicon regions harboring 20 core forensic STR loci in human benchmark samples HG002 and HG003. MacroHapCaller also was validated in whole‐genome long‐read sequencing data. Robust and accurate genotyping and phased macrohaplotypes were obtained with MacroHapCaller compared with the known ground truth. MacroHapCaller achieved a higher or consistent genotyping accuracy and faster speed than existing tools HipSTR and DeepVar. MacroHapCaller enables efficient macrohaplotype analysis from high‐throughput sequencing data and supports applications using discriminating macrohaplotypes.
Evaluating conservation units using network analysis: a sea duck case study
Authors: Lamb Juliet S , Cooper‐Mullin Clara , Gilliland Scott G , Berlin Alicia M , Bowman Timothy D , Boyd W Sean , De La Cruz Susan EW , Esler Daniel , Evenson Joseph R , Flint Paul , Lepage Christine , Meattey Dustin E , Osenkowski Jason E , Paton Peter WC , Perry Matthew C , Rosenberg Dan , Savard Jean‐Pierre L , Savoy Lucas , Schamber Jason , Ward David H , Takekawa John Y , McWilliams Scott R
Published: January 2024

Conserving migratory wildlife requires understanding how groups of individuals interact across seasons and landscapes. Telemetry reveals individual movements at large spatiotemporal scales; however, using movement data to define conservation units requires scaling up from individual movements to species‐ and community‐level patterns. We developed a framework to define flyways and identify important sites from telemetry data and applied it to long‐term, range‐wide tracking data from three species (640 individuals) of sea ducks: namely, North American scoters (Melanitta spp). Our network of 88 nodes included both multispecies hotspots and areas uniquely important to individual species. We found limited spatial overlap between scoters wintering on the Atlantic and Pacific coasts of North America, with differing connectivity patterns between coasts. Finally, we identified four multispecies conservation units that did not correspond to traditional management flyways. From this approach, we show how individual movements can be used to quantify range‐wide connectivity of migratory species and reveal gaps in conservation strategies.
Air pollution: a threat to insect pollination
Authors: Duque Laura , Steffan‐Dewenter Ingolf
Published: January 2024

Entomophilous plants rely on insects for pollination and consequently for reproduction. However, insect pollinators are facing multiple human‐driven pressures, from climate change to habitat loss to increased pesticide application. Anthropogenic activities have also led to critical increases in air pollution. A recent body of research focusing on the effects of air pollution on plant–pollinator interactions shows that air pollution might join the list of factors threatening insect pollination. Here, we examine the ways in which air pollution is thought to influence insect pollination, from potential mismatches between flowering and pollinator activity, to changes in pollinator attraction to flowers, to extensions in foraging periods. We consider the implications of these changes for plant reproduction and pollinator fitness and discuss how air pollutants are imperiling plant and pollinator communities. Finally, we define the questions that need to be addressed to better understand the impact of air pollution as a major driver of global change.
The agency of urban carnivores in human politics: leopards in Mumbai, India
Authors: Edelblutte Émilie , Short Gianotti Anne G , Gunnell Yanni
Published: January 2024

Across the world, increasing urbanization is leading to more frequent encounters between humans and wildlife. The resulting cohabitation promotes new human–wildlife dynamics in cities and requires innovative approaches for coping with wildlife in habitats that are not conventionally considered as suitable. Here we examined how leopards (Panthera pardus) acclimate to the urban environment in Mumbai, India, and influence human politics through their presence, adaptability, and diverse relationships with humans and nonhumans. Building on perspectives from political ecology and more‐than‐human geography, we show how leopards may thwart the outcomes of wildlife conservation and management and also catalyze transitions toward approaches that foster coexistence. We reveal the political role that leopards play in Mumbai by examining the many ways in which they influence power dynamics among humans. Our analysis illustrates how including considerations about the political agency of wildlife in urban planning can improve nature conservation and social policies.
How has the concept of resilience been applied in research across forest regions?
Authors: Strickland Mary K , Jenkins Michael A , Ma Zhao , Murray Bryan D
Published: January 2024

There are three common conceptualizations of resilience: persistence, recovery, and adaptability. While researchers apply all three in studies of forest ecosystems, the conceptualization used can have important empirical implications. We conducted a systematic literature review of empirical studies of forest resilience in the US from 2010 to 2020 to determine how researchers conceptualized, measured, and reflected the concept of resilience in reporting and interpreting their results. We determined that most studies defined resilience as recovery to the original state post‐disturbance, focused on the state of individual species within the ecosystem rather than the state of the ecosystem itself, and measured the impacts of a single disturbance rather than impacts of multiple disturbances. As climate change and other stressors exacerbate impacts to ecosystems, it is important to move beyond the persistence of or recovery to the original state as the goal for resilient ecosystems and to focus instead on maintaining ecosystem functions and enhancing their adaptability.
Baicalein, a dietary flavonoid, enhances the insulin‐sensitizing effect of metformin to prevent type 2 diabetes via the regulation of lipid metabolism and gut microenvironment
Authors: Xing Yan , Liu Haodong , Zhang Danyang , Jiang Hui , Xiu Zhilong , Dong Yuesheng
Published: January 2024

Baicalein is a natural flavonoid abundant in various foods and dietary plants, including Tuber aestivum and Oroxylum indicum. In this study, we investigated the role of baicalein in enhancing the insulin‐sensitizing effect of metformin in mice with prediabetes. Baicalein, when combined with 25% of normal‐dose metformin, achieved a diabetes‐reversion rate of 80%, which was 1.86‐fold that of normal‐dose metformin. Mechanistically, baicalein enhanced the insulin‐sensitizing effect of metformin on lipid metabolism by inhibiting de novo lipogenesis through the AMP‐activated protein kinase/SREBP‐1c/FASN pathway and by inducing fatty‐acid β‐oxidation through the upregulation of ACSL1, CPT1A, EHHADH, and acyl‐CoA dehydrogenases (ACADL/ACADM/ACADS). Meanwhile, baicalein enhanced the insulin‐sensitizing effect of metformin via the modulation of the gut microenvironment by enriching probiotics, especially Akkermansia by 53.4‐fold, depleting opportunistic pathogens, and strengthening the intestinal barrier. The improved gut microenvironment led to the alleviation of chronic endotoxemia, as evidenced by decreased levels of lipopolysaccharide and proinflammatory cytokines. Furthermore, baicalein enhanced the effect of metformin on decreasing the circulating level of branched‐chain amino acids (BCAAs), which further improved insulin sensitivity by normalizing the mTORC1/p70S6K/IRS1 signaling pathway and de novo lipogenesis. Moreover, the role of baicalein in enhancing the insulin‐sensitizing effect of metformin was verified by an oleic acid‐induced steatosis model and a BCAA‐induced insulin resistance model in hepatocytes. Our study laid a theoretical foundation for developing baicalein into a dietary supplement for diabetes prevention. The diverse mechanisms of food‐derived flavonoids can be applied in the development of dietary supplements to enhance the efficacy of oral hyperglycemic agents currently used in clinics.
Nurturing longevity through natural compounds: Where do we stand, and where do we go?
Authors: Todorova Monika N. , Savova Martina S. , Mihaylova Liliya V. , Georgiev Milen I.
Published: January 2024

The revolution in aging research through the past decade has driven the progress in interventions that promote longevity. Dissection of the “old” hallmarks of aging has provided solid data for the definition of at least three “new” ones, opening avenues for the development of novel hallmark‐targeted pro‐longevity approaches. The quest for geroprotectors is of enormous interest with the ultimate goal of finding the alchemical stone that induces healthy aging and increases lifespan, pushing the limits of human longevity or even uncovering the absence of such limits. Several of the well‐appreciated geroprotectors that are recognized as longevity promoters are of natural origin such as metformin, resveratrol, aspirin, and spermidine. As the search for pharmacological modulators of healthspan and lifespan continues, numerous studies are focusing on the potential of plant secondary metabolites. The current review attempts to critically assess the available interventions and the breakthrough discoveries in the field of longevity research over the past decade. Correspondingly, novel approaches targeting the hallmarks of aging have been outlined, and the future goals in longevity research have been enlightened. Special emphasis has been placed on the potential of plant‐derived compounds as pro‐longevity agents.
Cellulose nanofibers, nanocrystals, and bacterial nanocellulose: Fabrication, characterization, and their most recent applications
Authors: Rostamabadi Hadis , Bist Yograj , Kumar Yogesh , Yildirim‐Yalcin Meral , Ceyhan Tugce , Falsafi Seid Reza
Published: January 2024

In nature, cellulose is present in fibrillar structures with alternative crystalline and amorphous fragments. The application of various chemical treatments (acid hydrolysis, enzymolysis, and oxidation) could lead to the extraction and purification of crystalline compartments in the form of cellulose nanocrystals. On the other hand, applying harsh mechanical treatments (milling, ultrasonication, high‐pressure processing, grinding, microfluidization, etc.) could result in the degradation of cellulose macrostructures into nano‐fibrillated segments without depletion of the amorphous fractions. These structures are called cellulose nanofibers. Bacterial nanocelluloses (BNCs) are another nanostructure of cellulose that is generated through the bottom–up technique. BNCs are the purest forms of cellulose nanostructures (CNSs). Hitherto, various spectroscopy and microscopy characterization techniques have been developed for in‐depth investigation of CNSs. The valuable information obtained via such instrumental techniques has opened windows on new horizons for the application of CNSs in novel realms. Nowadays, CNSs have found a seat in biomedical, packaging, emulsification, water filtration, and textile applications. In this review, after describing various forms of CNSs and their fabrication methods, the most recent techniques that have been utilized for the characterization of these structures plus their current application in different realms are comprehensively overviewed.
Breast cancer screening awareness, practice, and perceived barriers: A community‐based cross‐sectional study among women in south‐eastern Bangladesh
Authors: Hoq Mohammad Injamul , Jahan Shamima , Mahmud Md. Hasan , Hasan Md. Mayin Uddin , Jakaria Md.
Published: January 2024

Background and Aims

Breast cancer is a leading cause of mortality in Bangladesh. An early‐stage screening is the best way to reduce both the morbidity and mortality burden of breast cancer. The study evaluated awareness, practice, and perceived barriers toward breast cancer screening in Bangladesh.

Methods

A community‐based cross‐sectional study was conducted from October 2021 to December 2022 in Chattogram, Bangladesh, where 869 women (18 years or above) were randomly selected in this study.

Results

Among 869 participants, 47.3% of women were recruited from urban areas and 52.7% participated from rural areas. Only 32.68% of respondents (urban vs. rural: 44.28% vs. 22.27%) were aware of breast self‐examination (BSE) and 52.47% of respondents (urban vs. rural: 63.75% vs. 42.36%) had ever heard Clinical Breast Examination (CBE), respectively. Among the respondents, 27.73% (urban vs. rural: 40.15% vs. 16.59%) performed their BSE, and only 14.61% of respondents (urban vs. rural: 21.90% vs. 8.08%) had ever visited for CBE. Women residing in rural areas were approximately three times (AOR: 0.36 [95% CI: 0.25–0.52], AOR: 0.37 [95% CI: 0.23–0.58]) less likely to perform BSE and CBE, respectively, than urban dwellers. We found that higher‐educated women tend to do more BSE and CBE than women with low levels of education. Perceptions of having “no symptoms” and being “risk‐free” are leading barriers to breast screening among women.

Conclusion

Poor awareness and practice were observed in screening among the urban and rural women in Bangladesh. Urban area dwellers had comparatively better understanding and practice than rural dwellers. We think extending health education and health promotion activities toward breast cancer screening is essential in this region.
Strategies for improving the financing of family medicine program: Evidence from Iran
Authors: Kabir Mohammad Javad , Moeini Sajad , Heidari Alireza
Published: January 2024

Background and Aims

The impact of health financing on the performance of the entire health system, including access, quality, and efficiency of healthcare, has been emphasized in the Astana Declaration, and the need to strengthen primary healthcare (PHC) and policy integration has been emphasized. After about two decades, the family medicine (FM) program in Iran is still facing great challenges. The aim of this study is to explore strategies for strengthening financing of the FM program in Iran, a vital component of PHC.

Methods

A qualitative study was conducted in 2021. Purposeful sampling was used to select 34 policymakers, managers, and experts from various levels of the Ministry of Health, Iran universities of medical sciences, plan and budget organization of Iran, and health insurance organization in Iran. Thirty‐four semistructured interviews were conducted to collect data, which were analyzed by content analysis.

Results

Through the analysis of interviews, our study has identified five strategies (identification and management of sustainable resources, pooling of sustainable resources, modeling of service provision, payment system model and its implementation process, and FM management structure), and 13 actions for strengthening financing of the FM program in Iran.

Conclusion

Our study has identified five strategies and 13 actions for strengthening the financing of the FM program in Iran. These strategies and actions should be considered by policymakers during the review of the FM program in Iran. Without implementation of the suggested strategies and action, allocated resources may be wasted.
The combined effect of split fueling strategy and EGR on the combustion, performance, and emission characteristics of a CRDI biofuel engine
Authors: Fernandes Lawrence Joseph , Rajashekhar Chandrashekharapura Ramachandraiah , Dinesha Pijakala
Published: January 2024

The current research investigates the impact of a split fueling strategy combined with several flow rates of exhaust gas recirculation (EGR) on the combustion and emission characteristics of a diesel engine running on B20 waste cooking oil (WCO) biodiesel. A four‐stroke single‐cylinder common rail direct injection engine was employed for experiments. It operates with a B20 blend of WCO biodiesel at 600 bar pressure for varying pilot fueling conditions of 10%, 20%, and 30%. The B20 blend with 30% pilot fuel injection (B20P30) showed excellent performance and emission characteristics compared with B20 blend with 10% pilot fuel injection (B20P10) and B20 with 20% pilot fuel injection (B20P20). However, B20P30 had greater levels of nitrogen oxide (NOx) emissions than those by diesel. EGR discharge levels in 5% increments, ranging from 0% to 15% were introduced to address this issue. The experimental findings revealed that both cylinder peak pressure and heat release rate showed a reduction when the EGR flow rate was enhanced. The recirculation of exhaust gas into the combustion chamber led to a slight increase in the emission levels of hydrocarbon (HC), carbon monoxide (CO), and smoke, as well as a decrease in carbon dioxide (CO2). Nevertheless, the introduction of EGR significantly decreased NOx emissions by 22.94%, 35.05%, and 47.96% for EGR flow rates of 5%, 10%, and 15%, respectively, when compared with the engine operating without EGR. Overall, the two‐stage fueling strategy, B20P30 blended with 10% EGR corroborated to be beneficial in reducing NOx emissions with minimal performance penalties. Although there was a slight uptick in certain emissions, the overall trade‐off between emission reduction and performance was favorable. The culmination of this study is targeting the objectives of sustainable development goal 7 (clean energy) and goal 13 (climate action) to be achieved by 2030.
Large‐scale physical facility and experimental dataset for the validation of urban drainage models
Authors: Sañudo E. , Cea L. , Puertas J. , Naves J. , Anta J.
Published: January 2024

Numerical models are currently the main tool used to simulate the effects of urban flooding. The validation of these models requires thorough and accurate observed data in order to test their performance. The current study presents a series of laboratory experiments in a large‐scale urban drainage physical facility of approximately 100 m2 that includes roofs, streets, inlets, manholes and sewers. The facility is equipped with a rainfall simulator as well as a surface runoff and pipe inflows generators. The experiments were divided in two sets. In Set 1 the surface runoff was generated exclusively by the rainfall input, while in Set 2 the rainfall simulator was used in combination with the runoff generators. In all the tests the water discharge was measured at points on the inlets, roofs, and outfall. The water depth at different locations of the facility was also measured. The experimental tests were replicated numerically using the urban drainage model Iber‐SWMM. Experimental results show that, even in a relatively small catchment the peaks in the hydrographs generated at each element of the facility during intermittent rainfalls are significantly attenuated at the catchment outlet. The agreement between the experimental and numerical results show that there are some differences in the hydrographs generated at each element, but that these differences compensate each other and disappear at the outfall. The results generated provide the research community with a thorough and high‐resolution dataset obtained under controlled laboratory conditions in a large‐scale urban drainage facility, something which has not previously been available.
Efficacy of dupilumab plus topical corticosteroids in children with atopic dermatitis: A meta‐analysis of randomized controlled trials
Authors: Wang Li , Wang Si‐Ning , Zhang Ruil‐Li
Published: January 2024

Introduction

Children with atopic dermatitis (AD) bear a significant burden of illness that adversely affects their quality of life.

Objective

To determine the efficacy of dupilumab and topical corticosteroids for the treatment of pediatric AD.

Methods

A comprehensive literature search was conducted using three prominent databases: Web of Science, PubMed, and Embase. Using a fixed‐effects or random‐effects model, the standard mean difference or risk ratios with 95% confidence intervals were calculated, and the trial protocol was listed as CRD42023408546.

Results

A total of 3 studies were included, and 896 participants met the inclusion criteria. The combined estimate showed that dupilumab plus topical corticosteroids had numerically greater efficacy in terms of Eczema Area and Severity Index (EASI)‐50, EASI‐75, EASI‐90, and Investigator Global Assessment (IGA) score of 0 or 1. Children who received topical corticosteroids and dupilumab achieved significantly higher Children's Dermatological Life Quality Index scores compared to those who received placebo. The number of individuals who achieved IGA 0/1 increased with the use of dupilumab and topical corticosteroids.

Conclusions

Dupilumab and topical corticosteroids can be used to treat symptoms in children with AD. However, given the substantial variation in treatment outcomes among studies, the findings should be interpreted with caution.
Sirtuin 3 is required for the dexmedetomidine‐mediated alleviation of inflammation and oxidative stress in nephritis
Authors: Lu Kai , Li Xinlong , Wu Jie
Published: January 2024

Introduction

Although sirtuin 3 (SIRT3) is known to be involved in dexmedetomidine (DEX)‐mediated alleviation of renal ischemia and reperfusion injury, the influence of the association between DEX and SIRT3 on nephritis development remains unclear. In this study, the role of SIRT3 in DEX‐mediated amelioration of inflammation and oxidative stress in nephritis as well as the possible underlying mechanism were explored in vivo and in vitro.

Methods

An animal model of glomerulonephritis was generated by injecting mice with interferon‐alpha (IFNα)‐expressing adenoviruses, and periodic acid–Schiff staining was then used to reveal pathogenicity‐related changes in the renal tissue. Additionally, human embryonic kidney cells (HEK293) and renal mesangial cells (RMCs) were treated with IFNα to establish cell models of inflammation in vitro.

Results

DEX administration alleviated glomerulonephritis in the animal model and upregulated SIRT3 expression in the renal tissue. SIRT3 knockdown inhibited the renoprotective effects of DEX against nephritis. IFNα induced inflammation, oxidative stress, and apoptosis in the RMCs and HEK293 cells and reduced their growth, as evidenced by the evaluation of cytokine levels (enzyme‐linked immunosorbent assay), reactive oxygen species generation, catalase and superoxide dismutase activities, nuclear factor‐erythroid factor 2‐related factor 2/heme oxygenase‐1 signal transduction, apoptotic cell proportion, and cell viability. In addition to promoting SIRT3 expression, DEX inhibited IFNα‐induced inflammation, oxidative stress, and apoptosis in these cells and promoted their viability. SIRT3 knockdown partially reversed the beneficial effects of DEX on RMCs and HEK293 cells.

Conclusions

Our results suggest that DEX exhibits renoprotective activity during nephritis progression, protecting renal cells against inflammatory injury by promoting SIRT3 expression.