bluuebunny/crossref_metadata_2025 huggingface dataset:
A mitochondrial DNA hypomorph of cytochrome oxidase specifically impairs male fertility in Drosophila melanogaster
Authors: Patel Maulik R , Miriyala Ganesh K , Littleton Aimee J , Yang Heiko , Trinh Kien , Young Janet M , Kennedy Scott R , Yamashita Yukiko M , Pallanck Leo J , Malik Harmit S
Published: August 2016

Due to their strict maternal inheritance in most animals and plants, mitochondrial genomes are predicted to accumulate mutations that are beneficial or neutral in females but harmful in males. Although a few male-harming mtDNA mutations have been identified, consistent with this ‘Mother’s Curse’, their effect on females has been largely unexplored. Here, we identify COIIG177S, a mtDNA hypomorph of cytochrome oxidase II, which specifically impairs male fertility due to defects in sperm development and function without impairing other male or female functions. COIIG177S represents one of the clearest examples of a ‘male-harming’ mtDNA mutation in animals and suggest that the hypomorphic mtDNA mutations like COIIG177S might specifically impair male gametogenesis. Intriguingly, some D. melanogaster nuclear genetic backgrounds can fully rescue COIIG177S -associated sterility, consistent with previously proposed models that nuclear genomes can regulate the phenotypic manifestation of mtDNA mutations.
First-principles study of the magnetism of Ni-doped MoS2 monolayer
Authors: Luo Min , Shen Yu Hao , Chu Jun Hao
Published: August 2016

The magnetic properties of Ni-doped monolayer MoS2 are investigated using the density function theory. The results show that two Ni-doped systems of the nearest-neighbor configuration are ferromagnetic. The p–d hybridization between the Ni dopant and its neighboring S atoms results in the splitting of energy levels near the Fermi energy. These results suggest the p–d hybridization mechanism for the magnetism of the Ni-doped MoS2 monolayer. The magnetic moment disappears with increasing Ni–Ni distance. Our studies predict the nearest two-Ni-doped MoS2 monolayers to be candidates for thin dilute magnetic semiconductors. Moreover, the formation energy calculations indicate that it would be easier to incorporate Ni atoms into a S-rich MoS2 monolayer in the experiment.
Chemistry Matters—From a Putative Peptide to Effective Treatments for Diabetes and Obesity
Authors: Mojsov Svetlana
Published: September 2024

In this Viewpoint, 2024 Lasker-DeBakey Clinical Medical Research Award winner Svetlana Mojsov describes her discovery of GLP-1 (7-37), the biologically active incretin that led to development of effective GLP-1 analogues for treating diabetes and obesity.
Discovery of cGAS as a DNA-Sensing Enzyme That Triggers Inflammation
Authors: Chen Zhijian J.
Published: September 2024

In this Viewpoint, 2024 Albert Lasker Basic Medical Research Award winner Zhijian J. Chen describes his discovery of cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS), a DNA-sensing enzyme that triggers inflammation.
Rogaratinib Plus Atezolizumab in Cisplatin-Ineligible Patients With FGFR RNA-Overexpressing Urothelial Cancer
Authors: Sweis Randy F. , Gajate Pablo , Morales-Barrera Rafael , Lee Jae-Lyun , Necchi Andrea , de Braud Filippo , Penel Nicolas , Grünwald Viktor , Maruzzo Marco , Meran Johannes , Ishida Tatiane Cristine , Bao Weichao , Zhou Yinghui , Ellinghaus Peter , Rosenberg Jonathan E.
Published: September 2024

Importance

The oral pan–fibroblast growth factor receptor inhibitor rogaratinib previously demonstrated encouraging safety and efficacy in a phase 1 study of patients with urothelial cancer (UC) overexpressing FGFR messenger RNA (mRNA).

Objective

To evaluate the safety, pharmacokinetics, and preliminary efficacy of rogaratinib in combination with the programmed cell death 1 ligand 1 (PD-L1) inhibitor atezolizumab in cisplatin-ineligible patients with FGFR mRNA-positive, locally advanced/metastatic UC.

Design, Setting, and Participants

The FORT-2 nonrandomized clinical trial was an open-label, single-arm, multicenter study conducted between May 15, 2018, and July 16, 2021, in 30 centers across Asia, Europe, and North America. Eligible patients had locally advanced/metastatic UC with FGFR1/3 mRNA overexpression and were ineligible for cisplatin-based chemotherapy. The data analysis was completed from July 2022 to September 2022.

Interventions

Patients received rogaratinib 600 mg or rogaratinib 800 mg twice daily in combination with intravenous atezolizumab 1200 mg every 21 days.

Main Outcomes and Measures

Primary end points included safety, tolerability, and the recommended phase 2 dose (RP2D) of rogaratinib in combination with atezolizumab.

Results

Among 153 patients screened, 73 (48%) had tumors with FGFR1/3 mRNA overexpression, and 37 patients were enrolled and treated (median [range] age, 75.0 [47.0-85.0] years; 32 [87%] male). The most common treatment-emergent adverse events (TEAEs) included diarrhea in 23 patients (62%), hyperphosphatemia in 19 (51%), and fatigue in 15 (41%). Grade 3 or higher TEAEs were reported in 27 patients (73%), and 4 grade 5 TEAEs were reported, though unrelated to treatment. The RP2D was rogaratinib 600 mg in combination with atezolizumab 1200 mg. At the RP2D, the overall response rate was 53.8% in the rogaratinib 600 mg group, including 4 patients (15%) with complete responses; 12 responders (86%) did not have an FGFR3 gene alteration, and 11 (79%) had low PD-L1 expression.

Conclusions and Relevance

In this phase 1b nonrandomized clinical trial, rogaratinib plus atezolizumab demonstrated a manageable safety profile, with no unexpected safety signals. Efficacy for this combination at the RP2D was observed in tumors with low PD-L1 and was not dependent on FGFR3 gene alterations, suggesting broad potential benefit for patients with locally advanced/metastatic UC and FGFR mRNA overexpression.

Trial Registration

ClinicalTrials.gov Identifier: NCT03473756
Potential Gaps in Eye Care Based on Evaluation of Federally Qualified Health Centers
Authors: Yadlapalli Nikhita , Hollinger Ruby , Berzack Shannan , Spies Daniela , Patel Annika , Sridhar Jayanth
Published: September 2024

Importance

Federally qualified health centers (FQHCs) are federally funded community health clinics that provide comprehensive care to underserved populations, making them potential opportunities to offer eye care and address unmet health care needs. Evaluating the presence of eye care services at FQHCs in Florida is important in understanding and addressing possible gaps in care for the state’s large uninsured and underserved populations.

Objective

To determine whether FQHCs in Florida are currently offering eye care services, where they are available, what services are being offered, and who provides them.

Design, Setting, and Participants

This study used a cross-sectional design conducted within 1 year (from November 2023 to February 2024). FQHCs listed in the US Health Resources and Services Administration database were contacted by telephone to inquire about the presence of eye care services. The FQHCs were located in both urban and rural areas in Florida to assess accessibility of eye care services in the state. School-based health centers and nonophthalmic specialty care health centers were excluded. A total of 437 FQHCs were included.

Main Outcomes and Measures

Primary outcomes included the presence of eye care services, types of services offered, clinician type (optometrists or ophthalmologists), frequency of services, and availability of pediatric services.

Results

Among 437 FQHCs contacted, only 39 (8.9%) reported offering eye care services. These services primarily included vision examinations, glasses prescriptions, and dilated eye examinations. Optometrists were the primary providers of services at all clinics, with no clinics reporting care by ophthalmologists. The frequency of services varied considerably, ranging from daily to bimonthly. Thirty-seven (94.9%) of the 39 clinics offered pediatric eye care services.

Conclusions and Relevance

The low prevalence of FQHCs with eye care services and the absence of ophthalmologist-provided care highlight a gap in access to eye care for underserved populations in Florida. These findings support investigations into implementing eye care services and interventions at FQHCs that might enhance access and equity in eye care.
Targeting ferroptosis for improved radiotherapy outcomes in HPV‐negative head and neck squamous cell carcinoma
Authors: Noh Joo Kyung , Lee Min Kyeong , Lee Yeonseo , Bae Minji , Min Soonki , Kong Moonkyoo , Lee Jung Woo , Kim Su Il , Lee Young Chan , Ko Seong‐Gyu , Woo Seon Rang , Eun Young‐Gyu
Published: September 2024

To enhance the efficacy of radiotherapy (RT) in human papillomavirus (HPV)‐negative head and neck squamous cell carcinoma (HNSCC), we explored targeting ferroptosis, a regulated cell death process. We developed a gene signature associated with ferroptosis using Cox proportional hazard modeling in HPV‐negative HNSCC patients who underwent RT. This ferroptosis‐related gene signature (FRGS) was a significant predictor of overall survival and recurrence‐free survival in HPV‐negative HNSCC patients who received RT. Subtype B of the FRGS, characterized by decreased expression of ferroptosis inducers [nuclear receptor coactivator 4 (NCOA4) and natural resistance‐associated macrophage protein 2 homolog/divalent metal transporter 1 (NRAMP2/DMT1)] and increased expression of suppressors [phospholipid hydroperoxide glutathione peroxidase (GPX4) and ferritin heavy chain (FTH1)], was associated with poorer prognosis, potentially indicating the inhibition of ferroptosis. Furthermore, our in vitro and in vivo studies demonstrated that treatment with statins, such as atorvastatin and simvastatin, induced ferroptosis and sensitized radioresistant HNSCC cells to irradiation, improving radiosensitivity and potentially enhancing the response to RT. Additionally, in xenograft models, the combination of statins and RT led to a significant reduction in tumor initiation. These findings provide valuable insights for enhancing treatment and improving prognosis in HPV‐negative HNSCC by targeting ferroptosis and utilizing statins to sensitize tumors to RT‐induced cell death.
Effect of Annealing Temperature on the Strength and Toughness of Ti‐55531 Titanium Alloy After Multiple Heat Treatment
Authors: Zhang Lei , Wang Jiangxiong , Wan Mingpan , Huang Chaowen , Lei Min , Ma Rui , Liu Dan , Ren Xianli , Li Tianxin
Published: September 2024

Herein, it is aimed to reveal the effect of annealing temperature on α microstructure parameters and mechanical properties of Ti‐55531 alloy under the multiple heat‐treatment process of “solution (855 °C) + annealing (700, 730, 760 °C) + aging (600 °C).” The microstructure is characterized by using optical microscopy, scanning electron microscopy, and transmission electron microscope. In the results, it is indicated that the annealing temperature does not change the volume fraction of the αs phase of Ti‐55531 alloy. The as‐annealed precipitation‐free zone αs phase renucleates after aging treatment, resulting in a bimodal distribution of αs phase in the matrix. The higher the annealing temperature, the larger the average size of αs phase and the greater the heterogeneity in the alloy. Additionally, the heterogeneity of αs phase affects further the plasticity and the crack propagation path of the alloy. With the increase of annealing temperature, the strength of Ti‐55531 alloy decreases slowly, but the elongation and the impact toughness of the alloy increases rapidly resulting from the heterogeneity of αs phase under multiple heat‐treatment conditions.
Pressure Visualization and Quantification Photonic Skin Based on Flexible Optical Fiber Combiner
Authors: Fang Jie , Zheng Hongyan , Yang Anping , Liu Haojun , He Yongcheng , Zhou Hongyou , Liu Luyan , Song Enhai , Guo Qianyi , Gan Jiulin , Yang Zhongmin
Published: September 2024

The integration of pressure quantification and visualization enhances pressure perception, accuracy, and efficiency. Current solutions require improvements in quantization accuracy, structural simplicity, and integration. We proposed a novel photonic skin comprising a 3 × 1 flexible optical fiber combiner, integrating red, green, and blue light emitting diode (LED) chips through three flexible optical fibers. Under pressure, changes in the optical fibers' transmission loss alter the output light intensity ratio, thus inducing a color shift at the combiner's output. This visible change can be precisely quantified using a color sensor chip. Performance metrics include sensing range up to 33N, sensitivity between 0.04 and 0.24 dB N−1, detection limit below 0.08 N, response time of 500 ms, recovery time of 400 ms, and durability exceeding 2000 cycles. A compact flexible circuit board manages light source driving, data acquisition, and wireless communication, forming a wearable photonic skin system. This system enables visual recognition and quantitative measurement of pressure across diverse scenarios, including different tactile modes, multi‐position pressure, finger bending, and neck movement. For oral occlusion force detection, the spatial separation of the sensing and visualization areas enables the system to simultaneously provide accurate measurements and intuitive visual assessment.
Qualitative Identification of the Spin‐to‐Orbital Conversion Mechanism Modulated by Rare‐Earth Nd, Gd, and Ho Metals via Terahertz Emission Measurements
Authors: Liu Long , Jiang Tianran , Zhao Xiaotian , Chen Ke , Lai Tianshu , Liu Wei , Zhang Zhidong
Published: September 2024

It is crucial to study the materials that could effectively facilitate the inter‐conversion between charge, spin, and orbital degrees of freedom. In this work, the conversion among these three types of degrees of freedom in Pt/CoFeB/rare‐earth (RE, represents Nd, Gd, and Ho)/Ti multilayers is manipulated. Through terahertz (THz) emission measurements, it is found that the spin current induced by a femtosecond laser is converted into an orbital current via the spin‐orbit coupling of the RE layer. Notably, the light RE (Nd) and heavy RE (Gd and Ho) induce the orbital current with opposite polarization directions, ultimately leading to a weakening or enhancement of the THz emission intensity, respectively. Moreover, the fast Fourier transform reveals that Gd exerts the most significant influence on increasing the whole THz spectrum within the Pt/CoFeB/RE/Ti structure. The findings of RE‐modulated spin‐to‐orbital conversion provide valuable insights into the fundamental transport mechanism of the orbital current.
BOIMPY Scaffold: Accessing Ultrahigh Molar Extinction Coefficient AIEgen for SWIR Imaging‐Guided Photothermal Cancer Ablation
Authors: Yang Mingwang , Ou Xinwen , Zhang Jianyu , Sun Jianwei , Kwok Ryan T. K. , Lam Jacky W. Y. , Fan Jiangli , Tang Ben Zhong
Published: September 2024

Despite the extensive reporting of versatile aggregation‐induced emission luminogens (AIEgens), boosting their molar extinction coefficient (MEC, ε ≈ 103–104 M−1cm−1) remains a formidable challenge, which poses a significant obstacle to achieving the ceiling of their output performance. In this work, an “aggrandizing absorption reservoir” approach is proposed to designing AIEgens with remarkable photons‐harvesting ability, ultimately enlarging its output performance in terms of short‐wave infrared (SWIR, 900–1700 nm) emission and photothermal effect. For the first time, the (bis‐(borondifluoride)‐8‐imidazodipyrromethene) (BOIMPY) unit, which provides sufficient rigidity and strong electron‐withdrawing ability by employing benzimidazole as a bridging ligand binding two BF2 units, is utilized to fabricate novel AIEgen (TPEB) that exhibits an ultrahigh MEC up to 1.29 × 105 M−1 cm−1 at 828 nm. To the best of knowledge, this is the highest MEC reported among AIEgens with near‐infrared absorption. Thanks to its remarkable photon‐harvesting ability, TPEB exhibits strong fluorescence in the SWIR region and a good photothermal effect. The as‐prepared TPEB NPs are successfully applied for SWIR imaging‐guided photothermal antitumor therapy. The proposed “aggrandizing absorption reservoir” approach provides a novel guideline for designing versatile AIEgens for biomedical applications.
High Entropy Helps Na4Fe3(PO4)2P2O7 Improve Its Sodium Storage Performance
Authors: Hu Xinyu , Li Houmou , Wang Zhihao , Liu Mingzu , Lu Yongyi , Zhang Yan , Li Jiajun , Ding Kun , Liu Haimei , Ma Zi‐Feng , Wang Yonggang
Published: September 2024

Recently, a high‐entropy strategy has attracted extensive attention and is applied to the preparation of electrode materials for energy storage batteries, aiming to improve electrochemical performance. It is found that adjusting the conformational entropy of the material can significantly enhance ion and electron transport efficiency, as well as improve the structural stability of the host material. However, there still remains a lack of deep understanding into the high‐entropy strategy, specifically regarding how this approach can alter the intrinsic properties of the material. In this work, the Na4Fe3(PO4)2P2O7 is designed and prepared as a model material with higher entropy, and ultimately, an optimized sample of Na3.9Fe2.6V0.1Mn0.1Cu0.1Mg0.1(PO4)2(P2O7) is achieved. The results indicate that increasing the entropy value of the material notably enhances its crystal structure, diffusion kinetics, and interfacial stability. Consequently, this optimized sample demonstrates deep insertion/extraction of 2.8 Na+, yielding an impressively high capacity of 122.3 mAh g−1 at 0.1C, alongside an ultra‐high rate capability of 100C. Remarkably, it also sustains performance over 14 000 cycles at 50C. This study underscores a method for fabricating high‐performance electrode materials through the implementation of the entropy strategy.
β‐Ga2O3 Nanoribbon with Ultra‐High Solar‐Blind Ultraviolet Polarization Ratio
Authors: Zhao Kai , Yang Juehan , Wang Pan , Zhou Ziqi , Long Haoran , Xin Kaiyao , Liu Can , Han Zheng , Liu Kaihui , Wei Zhongming
Published: September 2024

Solar‐blind ultraviolet (UV) detection plays a critical role in imaging and communication due to its low‐noise background, high signal‐to‐noise ratio, and strong anti‐interference capabilities. Detecting the polarization state of UV light can enhance image information and expand the communication dimension. Although polarization detection is explored in visible and infrared light, and applied in fields such as astrophysics and submarine seismic wave detection, solar‐blind UV polarization detection remains largely unreported. This is primarily due to the challenge of creating UV polarizers with high transmittance, high extinction ratio, and strong resistance to UV radiation. In this study, it is discovered that the space symmetry breaking of the β‐Ga2O3’s b–c plane results in a significant optical absorption dichroic ratio. Leveraging β‐Ga2O3’s high solar‐blind UV response, a lensless solar‐blind UV polarization‐sensitive photodetector, circumventing the challenges associated with solar‐blind UV polarizers is designed. This photodetector exhibits an exceptionally high intrinsic polarization ratio under 254 nm linearly polarized light, approximately two orders of magnitude higher than other reported nanomaterial‐based polarization‐sensitive photodetectors. Additionally, it demonstrates significant advantages in solar‐blind UV imaging and light communication. This work introduces a novel strategy for solar‐blind ultraviolet polarization detection and offers a promising approach for solar‐blind light communication.
Spectral Analysis on Color Detection Sharpness of Animal Vision toward Polychromatic Vision System
Authors: Lee Suyeon , Kim Hyochul , Kim Goohwan , Son Hyungbin , Kim Un Jeong
Published: September 2024

Spectral discrimination by animal visions such as human, bird, and butterfly is numerically compared by angular analysis of photo‐response (PR) which will be recorded at photo‐receptors. Hyperspectral imaging system is utilized to simulate various animal vision. Bird vision is acute to discriminate colors among different vegetables due to its evenly spaced and narrow spectral responsivity of photo‐receptors compared to that of human. Butterfly vision is excellent in discriminating red tomato ripening due to the exclusive photo‐receptors detecting only over 600 nm. Even real and fake fruits in the same perceived color for human is discriminated by bird vision. Artificial vision with finely resolved polychromatic artificial cone cells are demonstrated surpassing human vision using visible multispectral camera. This provides insights on designing novel bio‐inspired vision system.
Correlated evolution of dispersal traits and habitat preference in the melicgrasses
Authors: Brightly William H. , Bedoya Ana M. , Carlson McKenzie M. , Rottersman Maria G. , Strömberg Caroline A. E.
Published: September 2024

Premise

Seed dispersal is a critical process impacting individual plants and their communities. Plants have evolved numerous strategies and structures to disperse their seeds, but the evolutionary drivers of this diversity remain poorly understood in most lineages. We tested the hypothesis that the evolution of wind dispersal traits within the melicgrasses (Poaceae: Meliceae Link ex Endl.) was correlated with occupation of open and disturbed habitats.

Methods

To evaluate wind dispersal potential, we collected seed dispersal structures (diaspores) from 24 melicgrass species and measured falling velocity and estimated dispersal distances. Species’ affinity for open and disturbed habitats were recorded using georeferenced occurrence records and land cover maps. To test whether habitat preference and dispersal traits were correlated, we used phylogenetically informed multilevel models.

Results

Melicgrasses display several distinct morphologies associated with wind dispersal, suggesting likely convergence. Open habitat taxa had slower‐falling diaspores, consistent with increased wind dispersal potential. However, their shorter stature meant that dispersal distances, at a given wind speed, were not higher than those of their forest‐occupying relatives. Species with affinities for disturbed sites had slower‐falling diaspores and greater wind dispersal distances, largely explained by lighter diaspores.

Conclusions

Our results are consistent with the hypothesized evolutionary relationship between habitat preference and dispersal strategy. However, phylogenetic inertia and other plant functions (e.g., water conservation) likely shaped dispersal trait evolution in melicgrasses. It remains unclear if dispersal trait changes were precipitated by or predated changing habitat preferences. Nevertheless, our study provides promising results and a framework for disentangling dispersal strategy evolution.
Anchoring Catalytic Metal Nodes within a Single‐Crystalline Pyrazolate Metal‐Organic Framework for Efficient Heterogeneous Catalysis
Authors: Liang Rong‐Ran , Liu Zhaoyi , Han Zongsu , Yang Yihao , Rushlow Joshua , Zhou Hong‐Cai
Published: September 2024

The synthesis of single‐crystalline and robust pyrazolate metal–organic frameworks (Pz‐MOFs) capable of facilitating challenging organic transformations is fundamentally significant in catalysis. Here we demonstrate a metal‐node‐based catalytic site anchoring strategy by synthesizing a single‐crystalline and robust Pz‐MOF (PCN‐1004). PCN‐1004 features one‐dimensional (1D) copper‐Pz chains interconnected by well‐organized ligands, forming a porous three‐dimensional (3D) network with two types of 1D open channels. Notably, PCN‐1004 displays exceptional stability in aqueous solutions across a broad pH range (1 to 14), attributed to the robust copper‐Pz coordination bond. Significantly, PCN‐1004 functions as an outstanding catalyst in cross dehydrogenative coupling reactions for constructing C−O/C−S bonds, even in the absence of directing groups, achieving yields of up to ~99 %, with long cycle lives and high substrate compatibility. PCN‐1004 outperforms all previously reported porphyrin‐based homogeneous and heterogeneous catalysts. Control experiments and computations elucidate the pivotal catalytic role of the copper‐Pz chains and reveal a free radical pathway for the reaction. This work not only demonstrates the successful implementation of a metal‐node‐based catalytic site anchoring strategy for the efficient catalysis of challenging organic transformations but also highlights the synergistic effect of a robust framework, 1D open channels, and active sites in enhancing catalytic efficiency within MOFs.
Multi‐Stage Optimization of Pore Size and Shape in Pore‐Space‐Partitioned Metal–Organic Frameworks for Highly Selective and Sensitive Benzene Capture
Authors: Chen Yichong , Wang Wei , Alston Samuel , Xiao Yuchen , Ajayan Pooja , Bu Xianhui , Feng Pingyun
Published: September 2024

Compared to exploratory development of new structure types, pushing the limits of isoreticular synthesis on a high‐performance MOF platform may have higher probability of achieving targeted properties. Multi‐modular MOF platforms could offer even more opportunities by expanding the scope of isoreticular chemistry. However, navigating isoreticular chemistry towards best properties on a multi‐modular platform is challenging due to multiple interconnected pathways. Here on the multi‐modular pacs (partitioned acs) platform, we demonstrate accessibility to a new regime of pore geometry using two independently adjustable modules (framework‐forming module 1 and pore‐partitioning module 2). A series of new pacs materials have been made. Benzene/cyclohexane selectivity is tuned, progressively, from 4.5 to 15.6 to 195.4 and to 482.5 by pushing the boundary of the pacs platform towards the smallest modules known so far. The exceptional stability of these materials in retaining both porosity and single crystallinity enables single‐crystal diffraction studies of different crystal forms (as‐synthesized, activated, guest‐loaded) that help reveal the mechanistic aspects of adsorption in pacs materials.
1H NMR chemometrics and mechanistic insights on the thermal degradation of coconut oil
Authors: Flores Annabelle C. , Camacho Drexel H.
Published: September 2024

The re‐use and prolonged heating of cooking oils is a common practice in preparing deep‐fried foods. However, this could be unsafe and pose a health threat to consumers. This work investigates the thermal degradation of edible coconut oil under prolonged heating using chemometrics analysis of proton nuclear magnetic resonance (1H NMR) data. Coconut oil samples were heated continuously without food matrix at three different temperatures (150, 175, and 200°C) for 12 h and the 1H NMR spectra were collected every hour. NMR data revealed the formation of aldehyde oxidation products. Partial least squares discriminant analysis (PLS‐DA) discriminated the samples based on temperature and heating time. The Variable Importance Projection revealed the discriminating peaks highlighting the spectral feature due to hydroperoxides and aldehydes in the oil degradation. A probe into the 1H NMR of the degradation products of saturated coconut oil confirmed the formation of a ketone as evidenced by a CH2 triplet in the chemical shift region of protons alpha to a ketone. The results showed that the thermal degradation of coconut oil was influenced by temperature, time, moisture, and oxygen in the air which can contribute to the advancement in the control and assessment of coconut oil quality.
The influence of viscosity buildup on the foaming dynamics of rigid polyurethane foams
Authors: Cimavilla‐Román Paula , Álvarez‐Zapatero Pablo , Barroso‐Solares Suset , Vananroye Anja , Moldenaers Paula , Rodriguez‐Pérez Miguel Ángel
Published: September 2024

The viscoelastic properties development during the reactive foaming of four standard polyurethane formulations was monitored using a flooded parallel plate rheometer. The measurements in situ demonstrated how foams of low catalyst content took longer than 10 min to increase their viscosity from 1 to 103 Pa s, while foams with higher catalysts reached this modulus in less than 4 min. This polymerization speed deeply impacted the evolution of the cellular structure during foaming, which was demonstrated through in situ x‐ray imaging and computer simulation. Foams with high catalyst stabilized in their final cell size in 4–5 min, concurring with the stage of largest viscosity buildup. In contrast, the foams of low catalyst content underwent strong degeneration as a result of the slow gelification and stiffening of the matrix. Simulation results also revealed that stabilization of the cellular structure happens faster when the catalyst and blowing agent contents are increased.
Design, synthesis, evaluation, pharmacophore modeling, and 3D‐QSAR of lappaconitine analogs as potential analgesic agents
Authors: Wu Jingchuan , Lai Xiaohong , Zhang Yinyong , Li Yuzhu , Huang Shuai , Chen Lin , Zhou Xianli
Published: September 2024

Alleviating pain is crucial for patients with various diseases. This study aimed to enhance the analgesic properties of lappaconitine, a natural drug, through structural modifications. Specifically, carbamate analgesic active fragments were innovatively introduced at multiple sites on the benzene ring of lappaconitine. A total of 53 lappaconitine analogs were synthesized and evaluated. Compounds 5a, 5c, 5e, 6, and 15j addressed the narrow therapeutic window of lappaconitine, enhancing drug safety. Notably, carbamate analogs exhibited significantly enhanced analgesic activity, with compounds 5a and 5c having ED50 values of 1.2 and 1.6 mg/kg, respectively, indicating higher potency than lappaconitine (3.5 mg/kg). A metabolic analysis of compound 5e was conducted in mice, revealing its primary metabolic processes and metabolites, and providing preliminary exploration for the druggability. Given the multiple analgesic targets of lappaconitine, its analgesic mechanism remains inconclusive. This study, for the first time, analyzed the pharmacological activity characteristics of the lappaconitine analogs using a pharmacophore model and established a three‐dimensional quantitative structure–activity relationship (3D‐QSAR) to elucidate the quantitative relationship between the structures of the synthesized compounds and their analgesic activities. These findings provide valuable guidance for future structural modification and optimization of analgesic drugs.
Synergistic effects of biological stimuli and flexion induce microcavities promote hypertrophy and inhibit chondrogenesis during in vitro culture of human mesenchymal stem cell aggregates
Authors: Zhang Bo , Berilla Jim , Cho Sungwoo , Somoza Rodrigo A. , Welter Jean F. , Alexander Peter E. , Baskaran Harihara
Published: September 2024

Interzone/cavitation are key steps in early stage joint formation that have not been successfully developed in vitro. Further, current models of endochondral ossification, an important step in early bone formation, lack key morphology morphological structures such as microcavities found during development in vivo. This is possibly due to the lack of appropriate strategies for incorporating chemical and mechanical stimuli that are thought to be involved in joint development. We designed a bioreactor system and investigated the synergic effect of chemical stimuli (chondrogenesis‐inducing [CIM] and hypertrophy‐inducing medium [HIM]) and mechanical stimuli (flexion) on the growth of human mesenchymal stem cells (hMSCs) based linear aggregates under different conditions over 4 weeks of perfusion culture. Computational studies were used to evaluate tissue stress qualitatively. After harvesting, both Safranin‐O and hematoxylin & eosin (H&E) staining histology demonstrated microcavity structures and void structures in the region of higher stresses for tissue aggregates cultured only in HIM under flexion. In comparison to either HIM treatment or flexion only, increased glycosaminoglycan (GAG) content in the extracellular matrix (ECM) at this region indicates the morphological change resembles the early stage of joint cavitation; while decreased type II collagen (Col II), and increased type X collagen (Col X) and vascular endothelial growth factor (VEGF) with a clear boundary in the staining section indicates it resembles the early stage of ossification. Further, cell alignment analysis indicated that cells were mostly oriented toward the direction of flexion in high‐stress region only in HIM under flexion, resembling cell morphology in both joint cavitation and hypertrophic cartilage in growth plate. Collectively, our results suggest that flexion and HIM inhibit chondrogenesis and promote hypertrophy and development of microcavities that resemble the early stage of joint cavitation and endochondral ossification. We believe the tissue model described in this work can be used to develop in vitro models of joint tissue for applications such as pathophysiology and drug discovery.
CRISPR/Cas9‐based genome engineering in the filamentous fungus Rhizopus oryzae and its application to L‐lactic acid production
Authors: Zhu Haodong , Wang Han , Wang Li , Zheng Zhiming
Published: September 2024

The filamentous fungus Rhizopus oryzae is one of the main industrial strains for the production of a series of important chemicals such as ethanol, lactic acid, and fumaric acid. However, the lack of efficient gene editing tools suitable for R. oryzae makes it difficult to apply technical methods such as metabolic engineering regulation and synthetic biology modification. A CRISPR‐Cas9 system suitable for efficient genome editing in R. oryzae was developed. Firstly, four endogenous U6 promoters of R. oryzae were identified and screened with the highest transcriptional activity for application to sgRNA transcription. It was then determined that the U6 promoter mediated CRISPR/Cas9 system has the ability to efficiently edit the genome of R. oryzae through NHEJ and HDR‐mediated events. Furthermore, the newly constructed CRISPR‐Cas9 dual sgRNAs system can simultaneously disrupt or insert different fragments of the R. oryzae genome. Finally, this CRISPR‐Cas9 system was applied to the genome editing of R. oryzae by knocking out pyruvate carboxylase gene (PYC) and pyruvate decarboxylase gene (pdcA) and knocking in phosphofructokinase (pfkB) from Escherichia coli and L‐lactate dehydrogenase (L‐LDH) from Heyndrickxia coagulans, which resulted in a substantial increase in L‐LA production. In summary, this study showed that the CRISPR/Cas9‐based genome editing tool is efficient for manipulating genes in R. oryzae.
Redesigning glycolaldehyde synthase for the synthesis of biorefinery feedstock D‐xylulose from C1 compounds
Authors: Yan Yue , Zhao Haodong , Liu Dingyu , Zhang Jie , Liu Yuwan , Jiang Huifeng
Published: September 2024

Global climate deterioration intensifies the demand for exploiting efficient CO2 utilization approaches. Converting CO2 to biorefinery feedstock affords an alternative strategy for third‐generation biorefineries. However, upcycling CO2 into complex chiral carbohydrates remains a major challenge. Previous attempts at sugar synthesis from CO2 either produce mixtures with poor stereoselectivity or require ATP as a cofactor. Here, by redesigning glycolaldehyde synthase, the authors constructed a synthetic pathway for biorefinery feedstock D‐xylulose from CO2 that does not require ATP as a cofactor. The artificial D‐xylulose pathway only requires a three‐step enzyme cascade reaction to achieve the stereoselective synthesis of D‐xylulose at a concentration of 1.2 g L−1. Our research opens up an alternative route toward future production of chemicals and fuels from CO2.
Physics‐informed neural networks for biopharmaceutical cultivation processes: Consideration of varying process parameter settings
Authors: Adebar Niklas , Arnold Sabine , Herrera Liliana M. , Emenike Victor N. , Wucherpfennig Thomas , Smiatek Jens
Published: September 2024

We present a new modeling approach for the study and prediction of important process outcomes of biotechnological cultivation processes under the influence of process parameter variations. Our model is based on physics‐informed neural networks (PINNs) in combination with kinetic growth equations. Using Taylor series, multivariate external process parameter variations for important variables such as temperature, seeding cell density and feeding rates can be integrated into the corresponding kinetic rates and the governing growth equations. In addition to previous approaches, PINNs also allow continuous and differentiable functions as predictions for the process outcomes. Accordingly, our results show that PINNs in combination with Taylor‐series expansions for kinetic growth equations provide a very high prediction accuracy for important process variables such as cell densities and concentrations as well as a detailed study of individual and combined parameter influences. Furthermore, the proposed approach can also be used to evaluate the outcomes of new parameter variations and combinations, which enables a saving of experiments in combination with a model‐driven optimization study of the design space.
Masking level differences under two different measurement conditions: A normative study of young adults
Authors: Cekic Sule , Mujdeci Banu , Karakoc Kursad , Bas Banu
Published: September 2024

Objective

The objective of this study was to determine the gender‐specific normative values of masking level difference (MLD) in healthy young adults for two different measurement conditions.

Methods

One hundred young adults between the ages of 19 and 25 were included. Tympanometry, pure tone audiometry, and MLD were performed. In the first MLD measurement condition, the threshold level where the signal was out of phase and the noise was in phase (SπNo) was subtracted from the threshold level where the signal and noise were in phase (SoNo). In the second MLD measurement condition, the threshold level where the signal was in phase and the noise was out of phase (SoNπ) was subtracted from the threshold level where the signal and noise were in phase (SoNo). The mean test scores were obtained in decibels. Comparisons were made in terms of gender and conditions.

Results

The mean MLD for SoNo‐SπNo condition was 10.3 ± 1.99 dB. For SoNo‐SoNπ condition, the mean MLD was 6.72 ± 2.38 dB. A significant difference was determined between the MLD under two different measurement conditions (p <.05). There was no significant difference in terms of gender (p >.05).

Conclusion

Mean normative values of MLD test scores in gender‐specific healthy young adults for two different measurement conditions are presented.
Causal relationship between insomnia and thyroid disease: A bidirectional Mendelian randomization study
Authors: Li Zhonghui , Jia Zonghang , Zhou Peng , He Qingqing
Published: September 2024

Objective

Some correlations between thyroid disorders and insomnia have been found in previous studies; however, the causal relationship between them is unclear. The aim of this study was to investigate the causal relationship between insomnia and five thyroid disorders (hyperthyroidism, hypothyroidism, thyroiditis, thyroid nodules, and thyroid cancer).

Methods

We assessed the causal relationship between insomnia and thyroid disorders using inverse variance weighted, weighted median, and Mendelian randomization (MR)‐Egger analyses in MR analyses and then used inverse MR analyses to assess the causal relationship between thyroid disorders and insomnia.

Results

MR analysis showed that insomnia did not increase the risk of hyperthyroidism, hypothyroidism, thyroiditis, thyroid nodules, and thyroid cancer. However, reverse MR analysis showed that thyroid cancer increased the risk of insomnia (OR = 1.01, 95%CI: 1.00–1.02, p = .01), and the other four thyroid disorders had no direct causal relationship with insomnia. Sensitivity analyses indicated that the results were robust and no pleiotropy or heterogeneity was detected.

Conclusion

This study did not find evidence of a bidirectional causal relationship between genetically predicted insomnia and hyperthyroidism, hypothyroidism, thyroiditis, and thyroid nodules. However, we found that although insomnia does not increase the risk of thyroid cancer, thyroid cancer does increase the risk of insomnia.
The Pantropical Genus Rhynchosia Lour. (Fabaceae: Cajaninae): Diversity of Medicinal Uses, Phytochemistry, Pharmacology, and Toxicology
Authors: Ayokun‐nun Ajao Abdulwakeel , Calphonia Shilaluke Kolwane , Sonnyboy Mothogoane Mashiane , Ntsamaeeng Moteetee Annah
Published: September 2024

The pantropical genus Rhynchosia belongs to the family Fabaceae and consists of approximately 230 species distributed mainly in Africa, America, and Asia. Several species of the genus have been used ethnomedicinally since 300–400 AD. This review presents for the first time a global overview of the extent of ethnomedicinal uses of species in the genus in addition to their phytochemistry, pharmacological activities, and toxicology. Online databases such as NCBI, PubMed, Science Direct, Scopus, SpringerLink, Taylor and Francis Online, etc., were used to source for publications on Rhynchosia species. Based on this review, 30 species (19 %) are traditionally used for treating an array of ailments around the globe, most especially in Africa and Asia. Flavonoids are the most detected/isolated phytochemicals from the Rhynchosia species. Pharmacological activities such as anticancer, antidiabetic, anti‐hyperlipidemic, antifungal, antioxidant, anti‐inflammatory, antinociceptive, butyrylcholinesterase, as well as eye‐protective and melanogenic effects were elicited by the extracts and isolated compounds from Rhynchosia species. Toxicity tests have only been carried out on R. sublobata and R. elegans extracts. Future studies should focus on the toxicological evaluation and validation of ethnomedicinal claims on the traditional uses of Rhynchosia species that have not been pharmacologically tested.
Examining the reciprocal associations between symptoms of depression and anxiety and contact with the criminal justice system
Authors: Silver Ian A. , Schwartz Joseph A. , Allen Samantha L.
Published: September 2024

Background

Taken together, prior publications on the association between symptoms of depression and anxiety and contact with the criminal justice system (CJS) suggest a bi‐directional relationship, but all the studies only focus on one direction in this relationship.

Aims

To examine, in longitudinally collected data, period‐specific within‐individual change in anxiety and depression measures preceding arrest measurement and, separately, following arrest measurement.

Methods

Data were obtained from the National Longitudinal Study of Youth 1997, a nationally representative sample of people born between 1980 and 1984 and first interviewed between ages 12–17 and a publicly accessible database. Our focus was on data for the 11 years 2000–2010. Using whole sample data, we tested for a reciprocal association between depression and anxiety during each 2‐year period and arrests during the following year, and vice versa, allowing for relatively fixed characteristics such as sex, age and socio‐economic indicators. We used period‐specific change modelling to test relationships.

Results

We found that within‐individual increases in depression and anxiety scores over short periods (2‐year periods) of time was associated with an increase in the number of arrests subsequent over the following year, consistently throughout the whole of the 10 years studies. The reciprocal association was also observed, albeit the magnitude of the effects was much smaller.

Conclusion

This study adds to the literature on the association between mental health and CJS contact by showing that they may be reciprocally associated. This suggests that facilitating co‐working or even formal partnerships between community mental health services and justice‐related services could be beneficial.
Methods for treating coronary eruptive calcified nodules
Authors: Ashikaga Takashi , Lee Tetsumin , Miyazaki Ryoichi , Nagase Masashi , Misawa Toru , Kaneko Masakazu , Nozato Toshihiro
Published: September 2024

Eruptive calcified nodules (CNs) are a manifestation of severely calcified plaques, which exist in acute coronary syndrome (ACS), non‐ACS lesions. Optical coherence tomography is crucial for diagnosing and treating eruptive CNs in clinical practice. Management of eruptive CNs is still a challenge for interventional cardiologists. There have been significant advances in the treatment of eruptive CNs such as intravascular lithotripsy, excimer laser coronary atherectomy, rotational atherectomy, and orbital atherectomy. We find a range of treatment modalities to be effective under different conditions. The selection of these devices should be considered based on guidewire position, lesion characteristics, clinical manifestations, and operator's experiences.
Copper Catalyzed Fluoroalkyl‐Selenization of Olefins
Authors: Yu Jian‐Liang , Zhang Qing‐Qing , Zhang Yi‐Fan , Zuo Ya‐Wen , Jin Ruo‐Xing , Wang Xi‐Sheng
Published: September 2024

An efficient copper catalyzed fluoroalkyl‐selenization reaction of olefins has been developed, providing 1,2‐difluoroarylselenides in moderate to excellent yields. The readily available ethyl bromodifluoroacetate and diphenyl diselenide (Ph2Se2) have been employed as efficient radical precursor and selenization reagents to react with olefins. The reaction features a broad substrate scope, including substituted alkenes with various functional groups.
Chlorodefluorination Induced by Gallium‐Based Lewis Acids
Authors: Tölke Katharina , Neumann Beate , Stammler Hans‐Georg , Hoge Berthold
Published: September 2024

The reaction of [Ga(C2F5)3(FSiMe3)] with chlorotrimethylsilane leads to the selective substitution of the α‐fluorine atoms by chlorine atoms and thus to the formation of [Ga(CCl2CF3)3(FSiMe3)]. The corresponding chlorogallate ion, [Ga(CCl2CF3)3Cl]−, could be isolated and structurally characterized as its tetraphenylphosphonium salt. The catalytic potential of [Ga(CCl2CF3)3(FSiMe3)] was demonstrated via the chlorodefluorination of Me3SiCF3, 2,2‐difluoropropane and [PPh4][Ga(C2F5)4].
Steric hindrance and orientation polarization by a zwitterionic additive to stabilize zinc metal anodes
Authors: Wang Lu , Yu Huaming , Chen Dongping , Jin Youliang , Jiang Liangliang , He Hanwei , Zhou Gang , Xie Zeqiang , Chen Yuejiao
Published: September 2024

Zinc metal stands out as a promising anode material due to its exceptional theoretical capacity, impressive energy density, and low redox potential. However, challenges such as zinc dendrite growth, anode corrosion, and side reactions in aqueous electrolytes significantly impede the practical application of zinc metal anodes. Herein, 3‐(1‐pyridinio)‐1‐propanesulfonate (PPS) is introduced as a zwitterionic additive to achieve long‐term and highly reversible Zn plating/stripping. Due to the orientation polarization with the force of electric field, PPS additive with π–π conjugated pyridinio cations and strong coordination ability of sulfonate anion tends to generate a dynamic adsorption layer and build a unique water–poor interface. PPS with steric hindrance effect and strong coordination ability can attract solvated Zn2+, thereby promoting the desolvation process. Moreover, by providing a large number of nucleation sites and inducing zinc ion flow, the preferred orientation of the (002) crystal plane can be achieved. Therefore, the interfacial electrochemical reduction kinetics is regulated and uniform zinc deposition is ensured. Owing to these advantages, the Zn//Zn symmetrical cell with PPS additive exhibits remarkable cycling stability exceeding 2340 h (1 mA cm−2 and 1 mA h cm−2). The Zn//V2O5 full cell also delivers stable cycling for up to 6000 cycles.