bluuebunny/crossref_metadata_2025 huggingface dataset:
The Intracellular pH-regulatory HCO3−/Cl−Exchanger in the Mouse Oocyte Is Inactivated during First Meiotic Metaphase and Reactivated after Egg Activation via the MAP Kinase Pathway
Authors: Phillips Karen P. , Petrunewich Mary Ann F. , Collins Jennifer L. , Baltz Jay M.
Published: November 2002

The HCO3−/Cl−exchanger is quiescent in the unfertilized mouse egg but is highly active in regulating intracellular pH in the early embryo and required for normal development. We show here that the HCO3−/Cl−exchanger is active in first meiotic prophase (GV) oocyte but inactivated during meiotic metaphase before the MI to MII transition. Reactivation does not occur until the activated egg enters interphase. A quiescent HCO3−/Cl−exchanger is not simply a general feature of metaphase, because activity did not decrease during first mitotic metaphase. Inactivation of the HCO3−/Cl−exchanger during MI coincided with the activation of MAP kinase (MAPK), whereas its reactivation coincided with the loss of MAPK activity after egg activation. Maintaining high MAPK activity after egg activation prevented the normal reactivation of the HCO3−/Cl−exchanger. Inactivating MAPK in unfertilized MII eggs resulted in HCO3−/Cl−exchanger activation. Preventing MAPK activation during first meiotic metaphase prevented the inactivation of HCO3−/Cl−exchange. Conversely, activating MAPK in the GV oocyte resulted in inactivation of HCO3−/Cl−exchange. These results imply that the HCO3−/Cl−exchanger in mouse oocytes is negatively regulated by MAPK. Thus, suppression of pH-regulatory mechanisms during meiosis is a novel function of MAPK and cytostatic factor activity in the oocyte.
VIRIAL COEFFICIENTS FROM (2 + 1)-DIMENSIONAL QED EFFECTIVE ACTIONS AT FINITE TEMPERATURE AND DENSITY
Authors: BORGES P. F. , BOSCHI-FILHO H. , HOTT MARCELO
Published: November 2002

From spinor and scalar (2 + 1)-dimensional QED effective actions at finite temperature and density in a constant magnetic field background, we calculate the corresponding virial coefficients for particles in the lowest Landau level. These coefficients depend on a parameter θ related to the time-component of the gauge field, which plays an essential role for large gauge invariance. The variation of the parameter θ might lead to an interpolation between fermionic and bosonic virial coefficients, although these coefficients are singular for θ = π/2.
Directions in Evolutionary Biology
Authors: Lewontin R. C.
Published: November 2002

[Figure: see text]

▪ Abstract  In order to understand both the past and future directions of research in evolutionary biology we need to begin by understanding in what way these programs of research differ from the model of most scientific work. The study of evolutionary processes and, in particular, the genetics of the evolutionary process must confront special difficulties in both the conceptual and the methodological aspects of research. On the conceptual side, unlike for molecular, cellular, and developmental biology, there is no basic mechanism that evolutionists are attempting to elucidate. There is no single cause of the evolutionary change in the properties of members of a species. Natural selection may be involved but so are random events, patterns of migration and interbreeding, mutational events, and horizontal transfer of genes across species boundaries. The change in each character of each species is a consequence of a particular mixture of these causal pathways.
Analysis of Cardiovascular Phenotype and Genotype-Phenotype Correlation in Individuals With a
JAG1
Mutation and/or Alagille Syndrome
Authors: McElhinney Doff B. , Krantz Ian D. , Bason Lynn , Piccoli David A. , Emerick Karan M. , Spinner Nancy B. , Goldmuntz Elizabeth
Published: November 2002

Background—

Cardiovascular anomalies are among the most common features of Alagille syndrome (AGS). Mutations of
JAG1
are found in most individuals with AGS. This study was undertaken to determine the spectrum of cardiovascular phenotypes associated with a
JAG1
mutation and/or AGS, investigate potential genotype-phenotype correlations, and begin to correlate clinical outcome with genetic pathogenesis.

Methods and Results—

We reviewed the records of 200 individuals with a
JAG1
mutation or AGS. A total of 187 (94%) subjects had evidence of cardiovascular involvement. Cardiovascular anomalies were identified by imaging in 150 subjects (75%), and 37 (19%) had a peripheral pulmonary stenosis murmur with either a normal echocardiogram or no imaging study. Of the 150 subjects with anomalies confirmed by imaging, right-sided anomalies were present in 123 and left-sided anomalies in 22, with both in 12. Seventeen subjects had other anomalies. The most common abnormality was stenosis/hypoplasia of the branch pulmonary arteries (PAs), which was documented by imaging (n=111) or inferred from a peripheral pulmonary stenosis murmur (n=41) in 76% of subjects. Tetralogy of Fallot was present in 23 subjects and was accompanied by pulmonary atresia in 8. Branch PA phenotype differed between individuals with and without a
JAG1
mutation. Among subjects with a
JAG1
mutation, there was no correlation between the type or location of mutation and the frequency or type of cardiovascular anomaly.

Conclusions—

More than 90% of individuals with a
JAG1
mutation or AGS have cardiovascular anomalies, with branch PA stenosis the most common abnormality. Cardiovascular phenotype does not correlate with the type or location of
JAG1
mutation.
Low-Density Lipoprotein Level Reduction by the 3-Hydroxy-3-Methylglutaryl Coenzyme-A Inhibitor Simvastatin Is Accompanied by a Related Reduction of F
2
-Isoprostane Formation in Hypercholesterolemic Subjects
Authors: De Caterina Raffaele , Cipollone Francesco , Filardo Francesca Paola , Zimarino Marco , Bernini Walter , Lazzerini Guido , Bucciarelli Tonino , Falco Angela , Marchesani Paola , Muraro Raffaella , Mezzetti Andrea , Ciabattoni Giovanni
Published: November 2002

Background—

Both statins and vitamin E, by reducing the rate of lipid peroxidation, may interfere with oxidative stress, but the impact of their combination is unknown.

Methods and Results—

We randomized 43 hypercholesterolemic patients (21 men, 22 women, age 63±11 years) to either simvastatin, to achieve >20% reduction of total cholesterol, or simvastatin plus 600 mg/d vitamin E for 2 months. Patients were then crossed over to the alternative treatment. Lipid parameters documented patients’ compliance to simvastatin, whereas plasma levels of vitamin E documented compliance and absorption of vitamin E. We assessed urinary excretion of the isoprostane 8-iso-prostaglandin F
2α
(8-iso-PGF
2α
) as an in vivo index of oxidative stress at baseline and after each month of therapy. 8-Iso-PGF
2α
was significantly reduced by simvastatin, from 361±148 pg/mg creatinine (mean±SD) at baseline to 239±124 pg/mg creatinine after 1 month. The addition of vitamin E did not reduce such levels any further (256±125 after 1 month). Linear regression analysis showed a weak inverse relationship of 8-iso-PGF
2α
with vitamin E levels but a much stronger relationship with LDL cholesterol (
R
2
=0.162;
P
<0.001).

Conclusions—

In hypercholesterolemic patients, LDL cholesterol is a major correlate of oxidative stress. Concomitant with LDL cholesterol reduction, simvastatin causes a drastic reduction of oxidative stress to a level that is not further reduced by the addition of vitamin E. Results of clinical trials with vitamin E may have been hampered by inadequate knowledge of the background level of lipid peroxidation, which is a major determinant of vitamin E bioactivity.
Sympathetic Neural Activation in Visceral Obesity
Authors: Alvarez Guy E. , Beske Stacy D. , Ballard Tasha P. , Davy Kevin P.
Published: November 2002

Background—

Muscle sympathetic nerve activity (MSNA) is elevated in obese humans. However, the potential role of abdominal visceral fat as an important adipose tissue depot linking obesity to elevated MSNA has not been explored. Accordingly, we tested the hypothesis that MSNA would be increased in men (age=18 to 40 years, body mass index ≤35 kg/m
2
) with higher abdominal visceral fat (HAVF; n=13, abdominal visceral fat=118.1±15.8 cm
2
) compared with their age- (28.7±2.4 versus 25.5±2.0 years,
P
>0.05), total fat mass-matched (20.6±2.1 versus 20.8±2.4 kg,
P
>0.05) and abdominal subcutaneous fat-matched (230.6±24.9 versus 261.4±34.8 cm
2
,
P
>0.05) peers with lower abdominal visceral fat levels (LAVF; n=13, visceral fat= 73.0±6.0 cm
2
).

Methods and Results—

MSNA (microneurography), body composition (dual energy x-ray absorptiometry), and abdominal visceral and subcutaneous fat (computed tomography) were measured in 37 sedentary men across a wide range of adiposity. MSNA was ≈55% higher in men with HAVF compared with men with LAVF (33±4 versus 21±2 bursts/min,
P
<0.05). Furthermore, MSNA was more closely associated with the level of abdominal visceral fat (
r
=0.65,
P
<0.05) than total fat mass (
r
=0.323,
P
<0.05) or abdominal subcutaneous fat (
r
=0.27,
P
=0.05). The relation between MSNA and abdominal visceral fat was independent of total body fat (
r
=0.61,
P
<0.05).

Conclusions—

The results of our study indicate that MSNA is elevated in men with visceral obesity. Our observations are consistent with the idea that abdominal visceral fat is an important adipose tissue depot linking obesity with sympathetic neural activation in humans. Furthermore, these findings may have important implications for understanding the increased risk of developing cardiovascular diseases in individuals with visceral obesity.
Somatic and Germline Variants and Coronary Heart Disease in a Chinese Population
Authors: Zhao Kun , Shen Xuxiang , Liu Hongwei , Lin Zhennan , Li Jianxin , Chen Shufeng , Liu Fangchao , Huang Keyong , Cao Jie , Liu Xiaoqing , Shen Chong , Yu Ling , Zhao Yingxin , Zhao Liancheng , Li Ying , Hu Dongsheng , Huang Jiangfeng , Lu Xiangfeng , Gu Dongfeng
Published: January 2024

Importance

The genetic basis of coronary heart disease (CHD) has expanded from a germline to somatic genome, including clonal hematopoiesis of indeterminate potential (CHIP). How CHIP confers CHD risk in East Asian individuals, especially those with small clones (variant allele fraction [VAF] 0.5%-2%) and different genetic backgrounds, was completely unknown.

Objective

To investigate the CHIP profile in a general Chinese cohort by deep sequencing and further explore the association between CHIP and incident CHD considering germline predisposition.

Design, Setting, and Participants

This cohort study used data from 3 prospective cohorts in the project Prediction for Atherosclerotic Cardiovascular Disease Risk in China. Participants without cardiovascular disease or cancer at baseline were enrolled in 2001 and 2008 and had a median follow-up of 12.17 years extending into 2021.

Exposures

CHIP mutations were detected by targeted sequencing (mean depth, 916×). A predefined CHD polygenic risk score (PRS) comprising 531 variants was used to evaluate germline predisposition.

Main Outcomes and Measures

The main outcome was first incident CHD.

Results

Among 6181 participants, the median (IQR) age was 53.83 years (45.35-62.39 years); 3082 participants (49.9%) were female, and 3099 (50.1%) were male. A total of 1100 individuals (17.80%) harbored 1372 CHIP mutations at baseline. CHIP was independently associated with incident CHD (hazard ratio [HR], 1.42; 95% CI, 1.18-1.72; P = 2.82 × 10−4) and presented a risk gradient with increasing VAF (P = 3.98 × 10−3 for trend). Notably, individuals with small clones, nearly half of CHIP carriers, also demonstrated a higher CHD risk compared with non-CHIP carriers (HR, 1.33; 95% CI, 1.02-1.74; P = .03) and were 4 years younger than those with VAF of 2% or greater (median age, 58.52 vs 62.70 years). Heightened CHD risk was not observed among CHIP carriers with low PRS (HR, 1.02; 95% CI, 0.64-1.64; P = .92), while high PRS and CHIP jointly contributed a 2.23-fold increase in risk (95% CI, 1.51-3.29; P = 6.29 × 10−5) compared with non-CHIP carriers with low PRS. Interestingly, the diversity in CHIP-related CHD risk within each PRS group was substantially diminished when removing variants in the inflammatory pathway from the PRS.

Conclusions

This study revealed that elevated CHD risk attributed to CHIP was nonnegligible even for small clones. Inflammation genes involved in CHD could aggravate or abrogate CHIP-related CHD risk.
Factors Affecting Treatment Selection Among Patients With Hidradenitis Suppurativa
Authors: Salame Nicole , Sow Yacine N. , Siira Meron R. , Garg Amit , Chen Suephy C. , Patzer Rachel E. , Kavalieratos Dio , Orenstein Lauren A. V.
Published: January 2024

Importance

Despite the US Food and Drug Administration’s approval of adalimumab for the treatment of hidradenitis suppurativa (HS), prescription rates remain low, indicating a critical gap between evidence-based guidelines and clinical practice. Understanding the medical decision-making process that these patients use when considering biologic agents and other HS therapies may uncover opportunities for improved patient-physician communication and HS disease control.

Objective

To elucidate factors that affect the medical decision-making process for patients with HS, with an emphasis on biologic therapies.

Design, Setting, and Participants

Open-ended semistructured interviews were conducted with English-speaking adults with HS (aged ≥18 years) recruited from 2 dermatology clinics that are part of Emory University School of Medicine in Atlanta, Georgia. All participants had an average 7-day pain score of 1 or higher on a 0- to 10-point numeric rating scale. Surveys were conducted between November 2019 and March 2020, and data were analyzed from December 2021 to August 2022. Data collection continued until thematic saturation was reached at 21 interviews.

Results

A total of 21 participants (median [IQR] age, 38.5 [27.9-43.4] years; 16 females [76%]) were included in the analysis. Almost all participants (96%) had Hurley stage II or III disease, and 15 (71%) had a history of adalimumab use. Suffering threshold, perceptions of treatment risk, treatment fatigue, disease understanding, and sources of information (included dermatologists, the internet, advertisements, and friends and loved ones) were identified as factors affecting participants’ decisions to initiate new treatments for HS.

Conclusions and Relevance

Results of this qualitative study suggest that mitigating misconceptions about treatment risk, identifying gaps in disease knowledge, and emphasizing early treatment to prevent scarring and disease progression may empower patients with HS to engage in treatment planning and to try new therapies.
Addressing asymmetric saturation in chaotic Chua's circuit switched system: A combined adaptive sliding mode strategy
Authors: Amiri Saeed , Seyed Moosavi Seyed Mohsen , Forouzanfar Mehdi , Aghajari Ebrahim
Published: January 2024

The purpose of this research is to develop a combined adaptive nonlinear feedback integral sliding mode (CANFISM) for the Chua's switched nonlinear circuit systems. The suggested adaptive composite nonlinear technique is improved to provide a robust controller with enhanced performance in the face of uncertainty and asymmetric saturation. The proposed technique has been theoretically validated, and its closed‐loop exponentially boundedly stable has been demonstrated. Meanwhile, CNF (composite nonlinear feedback) parameters are then determined by employing the linear matrix inequality technique, and the notion of robust tracking is performed and compared in Chua's switched nonlinear circuit systems. This method guarantees robustness against the effects of uncertainty and input asymmetric saturation and decreases chattering. The effectiveness and merits of the suggested technique are then achieved by utilizing two simulation examples of Chua's circuit system.
Reconfigurable and Parallel Computable Soft Mechanical Switch by Liquid Metal
Authors: Li Xin‐Yang , Hu Zu‐An , Liu Qian , Xie Tian , Wang Xian‐Wen , Huang Lu , Wu Ying‐Peng
Published: January 2024

Introducing soft materials with deformability and flexibility into mechanical switches may help to develop new types of soft mechanical switches with special properties such as reconfigurable characteristics and parallel computing. However, recently developed soft mechanical switches still have low on/off ratio, slow response time, and insufficient durability. Here, a soft mechanical switch based on liquid metal and a zigzag structure is constructed through strain engineering strategy with high on/off ratio (R/R0 > 107), short response time (~0.2 s), long‐term durability (> 2000 times), and self‐healing performance which is outstanding than the reported ones. With the switch, a mechanical unit is designed and all types of logic gates can be constructed by programming switches. Such multiple switches can also be used to perform parallel computing and achieve intelligent information processing.
Hybrid Cellulose‐Based Systems for Triboelectrification in Aerosol Filtration, Ammonia Abatement and Respiration Monitoring
Authors: Ding Zhaodong , Tian Zhongjian , Ji Xingxiang , Yang Guihua , Sameer Mhatre , Lu Yi , Rojas Orlando J.
Published: January 2024

The dissipation of charges by aging or under the effect of humid conditions considerably impedes a broader utilization of electrostatic fields in aerosol filtration. This study introduces a respiration‐driven air filter (RAF) that continuously generates triboelectric charges within a pair of tribolayers, which facilitates a sustained filtration performance. Such system is integrated in a multilayer unit that is inserted in personal protective equipment (RAFM) to efficiently capture, sense, and degrade airborne pollutants with no need for external power sources. The triboelectric nanogenerator‐based RAF continuously replenishes static charges and maintains an electrostatic field through breathing by the effect of contact‐electrification between two cellulose‐based tribolayers: a cellulose/metal organic framework cryogel (electron donor) and a cellulose–based electrospun membrane (electron acceptor). Notably, the triboelectric field of the RAF's tribolayer pair substantially enhances both the filtration efficiency (up to 93.8% for 0.3 µm particulate matter) and sensing/catalytic degradation (ammonia; degradation >20%). When integrated in a circuit module, the RAFM effectively monitors respiration dynamics, acting as a breathing indicator/regulator. Overall, this study adds to the promise of tribogeneration through cellulose‐based materials and its application in exposure‐risk operations.
Local and Sustained Baricitinib Delivery to the Skin through Injectable Hydrogels Containing Reversible Thioimidate Adducts
Authors: Wang Leo L. , Tuohy Spencer , Xu Karen L. , Nace Arben , Yang Ruifeng , Zheng Ying , Burdick Jason A. , Cotsarelis George
Published: January 2024

Janus kinase (JAK) inhibitors are approved for many dermatologic disorders, but their use is limited by systemic toxicities including serious cardiovascular events and malignancy. To overcome these limitations, injectable hydrogels are engineered for the local and sustained delivery of baricitinib, a representative JAK inhibitor. Hydrogels are formed via disulfide crosslinking of thiolated hyaluronic acid macromers. Dynamic thioimidate bonds are introduced between the thiolated hyaluronic acid and nitrile‐containing baricitinib for drug tethering, which is confirmed with1H and13C nuclear magnetic resonance (NMR). Release of baricitinib is tunable over six weeks in vitro and active in inhibiting JAK signaling in a cell line containing a luciferase reporter reflecting interferon signaling. For in vivo activity, baricitinib hydrogels or controls are injected intradermally into an imiquimod‐induced mouse model of psoriasis. Imiquimod increases epidermal thickness in mice, which is unaffected when treated with baricitinib or hydrogel alone. Treatment with baricitinib hydrogels suppresses the increased epidermal thickness in mice treated with imiquimod, suggesting that the sustained and local release of baricitinib is important for a therapeutic outcome. This study is the first to utilize a thioimidate chemistry to deliver JAK inhibitors to the skin through injectable hydrogels, which has translational potential for treating inflammatory disorders.
Injectable Hydrogels with Integrated Ph Probes and Ultrasound‐Responsive Microcapsules as Smart Wound Dressings for Visual Monitoring and On‐Demand Treatment of Chronic Wounds
Authors: Huang Da , Du Jiahao , Luo Fang , He Gang , Zou Minglang , Wang Yongming , Lin Zhenyu , Wu Decheng , Weng Zuquan
Published: January 2024

Hydrogel dressings capable of infection monitoring and precise treatment administration show promise for advanced wound care. Existing methods involve embedd ingorganic dyes or flexible electronics into preformed hydrogels, which raise safety issues and adaptability challenges. In this study, an injectable hydrogel based smart wound dressing is developed by integrating food‐derived anthocyanidin as a visual pH probe for infection monitoring and poly(L‐lactic acid) microcapsules as ultrasound‐responsive delivery systems for antibiotics into a poly(ethylene glycol) hydrogel. This straightforwardly prepared hydrogel dressing maintains its favorable properties for wound repair, including porous morphology and excellent biocompatibility. In vitro experiments demonstrated that the hydrogel enabled visual assessment of pH within the range of 5 ∼ 9.Meanwhile, the release of antibiotics could be triggered and controlled by ultrasound. In vivo evaluations using infected wounds and diabetic wounds revealed that the wound dressing effectively detected wound infection by monitoring pH levels and achieved antibacterial effects through ultrasound‐triggered drug release. This led to significantly enhanced wound healing, as validated by histological analysis and the measurement of inflammatory cytokine levels. This injectable hydrogel‐based smart wound dressing holds great potential for use in clinical settings to inform timely and precise clinical intervention and in community to improve wound care management.
Charge Carrier Induced Structural Ordering And Disordering in Organic Mixed Ionic Electronic Conductors
Authors: Quill Tyler J. , LeCroy Garrett , Marks Adam , Hesse Sarah A. , Thiburce Quentin , McCulloch Iain , Tassone Christopher J. , Takacs Christopher J. , Giovannitti Alexander , Salleo Alberto
Published: January 2024

Operational stability underpins the successful application of organic mixed ionic‐electronic conductors (OMIECs) in a wide range of fields, including biosensing, neuromorphic computing, and wearable electronics. In this work, both the operation and stability of a p‐type OMIEC material of various molecular weights are investigated. Electrochemical transistor measurements reveal that device operation is very stable for at least 300 charging/discharging cycles independent of molecular weight, provided the charge density is kept below the threshold where strong charge–charge interactions become likely. When electrochemically charged to higher charge densities, an increase in device hysteresis and a decrease in conductivity due to a drop in the hole mobility arising from long‐range microstructural disruptions are observed. By employing operando X‐ray scattering techniques, two regimes of polaron‐induced structural changes are found: 1) polaron‐induced structural ordering at low carrier densities, and 2) irreversible structural disordering that disrupts charge transport at high carrier densities, where charge–charge interactions are significant. These operando measurements also reveal that the transfer curve hysteresis at high carrier densities is accompanied by an analogous structural hysteresis, providing a microstructural basis for such instabilities. This work provides a mechanistic understanding of the structural dynamics and material instabilities of OMIEC materials during device operation.
Bending and Stretching‐Insensitive, Crosstalk‐Free, Flexible Pressure Sensor Arrays for Human‐Machine Interactions
Authors: Yuan Yangbo , Xu Hongcheng , Zheng Weihao , Liu Min , Li Sixin , Yan Junyu , Wang Daren , Liu Ke , Zhang Haiyan , Chen Gang , Wang Weidong , Wu Guirong , Xue Chenyang , Cheng Huanyu , Gao Libo
Published: January 2024

Accurate data acquisition from flexible sensors placed on deformable 3D freeform surfaces is of critical importance for many applications, such as wearable electronics, human‐machine interfaces, and soft robotics. However, the mechanical coupling between the sensor and the deformable subject surface to bending and stretching deformations can significantly reduce the accuracy of the acquired data. This study combines a polyimide (PI) micropore isolation layer (PIL) and serpentine electrodes with a flexible piezoresistive sensor to mitigate the issue of mechanical coupling. As a mechanical buffer to distribute the external pressure and reduce the strain concentration, the PIL can avoid the bending interference for bending curvature up to 256 m−1, while maintaining a high sensitivity of S > 21.5 kPa−1. The serpentine electrode design further allows the sensor to reliably acquire data in the presence of stretching up to 45% without cross‐talk. The versatility of the developed sensor is demonstrated in several human‐machine interaction scenarios, including gesture recognition and motion detection. The design strategies on materials and structures from this study can also be applied for the development of other flexible sensors with high sensitivity and low deformation interference to avoid the mechanical coupling between the sensor and the deformable surface.
Visible‐Light‐Promoted Difluoromethylation/Cyclization of 1‐Acryloyl‐2‐cyanoindole for Construction of Difluoromethylated Pyrrolo[1,2‐a]indolediones
Authors: Qu Hongzhao , Yuan Jinwei , Feng Zhendong , Guo Na , Yin Yanli , Yang Liangru , Xiao Yongmei , Qu Lingbo
Published: January 2024

A visible‐light‐promoted cascade difluoromethylation/cyclization reaction to access various difluoromethylated pyrrolo[1,2‐a]indolediones was developed using difluoromethyltriphenylphosphonium bromide salt as the difluoromethylating reagent. A possible radical mechanism has been investigated and proven as a single electron transfer (SET) procedure.
Inhibition of NFAT5‐Dependent Astrocyte Swelling Alleviates Neuropathic Pain
Authors: He Liqiong , Ma Shengyun , Ding Zijin , Huang Zhifeng , Zhang Yu , Xi Caiyun , Zou Kailu , Deng Qingwei , Huang Wendy Jia Men , Guo Qulian , Huang Changsheng
Published: January 2024

Astrocyte swelling is implicated in various neurological disorders. However, whether astrocyte swelling contributes to neuropathic pain remains elusive. This study elucidates the pivotal role of the nuclear factor of activated T‐cells 5 (NFAT5) emerges as a master regulator of astrocyte swelling in the spinal dorsal horn (SDH) during neuropathic pain. Despite the ubiquitous expression of NFAT5 protein in SDH cell types, it selectively induces swelling specifically in astrocytes, not in microglia. Mechanistically, NFAT5 directly controls the expression of the water channel aquaporin‐4 (AQP4), a key regulator exclusive to astrocytes. Additionally, aurora kinase B (AURKB) orchestrates NFAT5 phosphorylation, enhancing its protein stability and nuclear translocation, thereby regulating AQP4 expression. The findings establish NFAT5 as a crucial regulator for neuropathic pain through the modulation of astrocyte swelling. The AURKB‐NFAT5‐AQP4 pathway in astrocytes emerges as a potential therapeutic target to combat neuropathic pain.
De Novo Generation and Identification of Novel Compounds with Drug Efficacy Based on Machine Learning
Authors: He Dakuo , Liu Qing , Mi Yan , Meng Qingqi , Xu Libin , Hou Chunyu , Wang Jinpeng , Li Ning , Liu Yang , Chai Huifang , Yang Yanqiu , Liu Jingyu , Wang Lihui , Hou Yue
Published: January 2024

One of the main challenges in small molecule drug discovery is finding novel chemical compounds with desirable activity. Traditional drug development typically begins with target selection, but the correlation between targets and disease remains to be further investigated, and drugs designed based on targets may not always have the desired drug efficacy. The emergence of machine learning provides a powerful tool to overcome the challenge. Herein, a machine learning‐based strategy is developed for de novo generation of novel compounds with drug efficacy termed DTLS (Deep Transfer Learning‐based Strategy) by using dataset of disease‐direct‐related activity as input. DTLS is applied in two kinds of disease: colorectal cancer (CRC) and Alzheimer's disease (AD). In each case, novel compound is discovered and identified in in vitro and in vivo disease models. Their mechanism of actionis further explored. The experimental results reveal that DTLS can not only realize the generation and identification of novel compounds with drug efficacy but also has the advantage of identifying compounds by focusing on protein targets to facilitate the mechanism study. This work highlights the significant impact of machine learning on the design of novel compounds with drug efficacy, which provides a powerful new approach to drug discovery.
Hepatic‐Accumulated Obeticholic Acid and Atorvastatin Self‐Assembled Nanocrystals Potentiate Ameliorative Effects in Treatment of Metabolic‐Associated Fatty Liver Disease
Authors: Lu Huanfen , Ban Zhenglan , Xiao Kai , Sun Madi , Liu Yongbo , Chen Fangman , Shi Tongfei , Chen Li , Shao Dan , Zhang Ming , Li Wei
Published: January 2024

Exploration of medicines for efficient and safe management of metabolic‐associated fatty liver disease (MAFLD) remains a challenge. Obeticholic acid (OCA), a selective farnesoid X receptor agonist, has been reported to ameliorate injury and inflammation in various liver diseases. However, its clinical application is mainly limited by poor solubility, low bioavailability, and potential side effects. Herein a hepatic‐targeted nanodrugs composed of OCA and cholesterol‐lowering atorvastatin (AHT) with an ideal active pharmaceutical ingredient (API) content for orally combined treatment of MAFLD is created. Such carrier‐free nanocrystals (OCAHTs) are self‐assembled, not only improving the stability in gastroenteric environments but also achieving hepatic accumulation through the bile acid transporter‐mediated enterohepatic recycling process. Orally administrated OCAHT outperforms the simple combination of OCA and AHT in ameliorating of liver damage and inflammation in both acetaminophen‐challenged mice and high‐fat diet‐induced MAFLD mice with less systematic toxicity. Importantly, OCAHT exerts profoundly reverse effects on MAFLD‐associated molecular pathways, including impairing lipid metabolism, reducing inflammation, and enhancing the antioxidation response. This work not only provides a facile bile acid transporter‐based strategy for hepatic‐targeting drug delivery but also presents an efficient and safe full‐API nanocrystal with which to facilitate the practical translation of nanomedicines against MAFLD.
Black Phosphorene with Removable Aluminum Ion Protection for Enhanced Electrochemical Nitrogen Fixation
Authors: Lai Jinhua , Liu Honghong , Ding Liang‐Xin , Wang Junjie , Chen Gao‐Feng , Wang Haihui
Published: January 2024

The exceptional electronic properties and potential applications of black phosphorus (BP) have garnered significant interest in the fields of electrochemical catalysis and energy storage. However, its poor environmental stability severely hampers its practical use. In this study, an innovative strategy is proposed to protect fresh black phosphorene (BPene) against oxidation by adsorbing or weakly bonding aluminum ions (Al3+) onto its surface, while facilitating their self‐removal under operating conditions. By leveraging Al3+‐protected black phosphorene (Al‐BPene) as a catalyst for the electrocatalytic reduction of nitrogen to ammonia (NH3), the effectiveness of this removable Al3+‐protected strategy is demonstrated. Quantitative analysis reveals that Al‐BPene maintains structural and compositional stability for over 7 days under ambient conditions, while the Al3+ can be readily eliminated through self‐desorption or dissolution in the electrolyte. With highly active sites pre‐protected, Al‐BPene exhibits a striking NH3 yield rate of 55.1 µg h−1 mg cat−1 and a Faradaic efficiency (FE) of 66.5% in alkaline media, as exemplified by the representative application example. Moreover, it is found that the prepared Al‐BPene can tolerate a thermal environment, and a higher NH3 yield rate of 75 µg h−1 mg cat−1 at 60 °C is recorded. Undoubtedly, these findings pave the way for broader applications of BPene.
Synergistic Crystallization Kinetics Modulation and Deep/Shallow Level Defect Passivation via an Organometallic Cobaltocenium Salt Toward High‐Performance Inverted Perovskite Solar Cells
Authors: Pu Xingyu , Cao Qi , He Xilai , Su Jie , Wang Weiwei , Zhang Xue , Wang Dapeng , Zhang Yixin , Yang Jiabao , Wang Tong , Chen Hui , Jiang Long , Yan Yi , Chen Xingyuan , Li Xuanhua
Published: January 2024

Numerous deep/shallow level defects generated at the surface/grain boundaries of perovskite during uncontrollable crystallization pose a formidable challenge to the photovoltaic performance of perovskite solar cells (PSCs). Herein, an organometallic cobaltocenium salt additive, 1‐propanol‐2‐(1,2,3‐triazol‐4‐yl) cobaltocenium hexafluorophosphate (PTCoPF6), is incorporated into the perovskite precursor solution to regulate crystallization and minimize holistic defects for high‐performance inverted PSCs. The cobaltocenium cations and PF6− in PTCoPF6 stabilize the Pb‐I framework and repair the shallow‐level defects of positively and negatively charged vacancies in the perovskite. The N═N in the triazole ring of PTCoPF6 can passivate the deep‐level defects of uncoordinated lead. The interaction between PTCoPF6 and perovskite materials delays perovskite nucleation and crystal growth, ensuring high‐quality perovskite with large grains, and suppressing non‐radiative recombination and ion migration. Therefore, the PTCoPF6‐incorporated PSC achieves an impressive power conversion efficiency of 25.03% and outstanding long‐term stability. Unencapsulated and encapsulated PTCoPF6‐incorporated PSCs maintain 93% and 95% of their initial efficiencies under 85 °C storage in a nitrogen atmosphere for 1000 h and maximum power point tracking for nearly 1000 h, respectively. Synergistic crystallization kinetic modulation and deep/shallow level defect passivation with ionized metal‐organic complex additives will become prevalent methods to improve the efficiency and stability of PSCs.
25‐Year fatal workplace suicide trends in North Carolina: 1992–2017
Authors: Martin Chelsea L. , Richey Morgan , Richardson David B. , Nocera Maryalice , Cantrell John , McClure Elizabeth S. , Martin Amelia T. , Marshall Stephen W. , Ranapurwala Shabbar I.
Published: January 2024

Background

Suicide is a serious public health problem in the United States, but limited evidence is available investigating fatal suicides at work. There is a substantial need to characterize workplace suicides to inform suicide prevention interventions and target high‐risk settings. This study aims to examine workplace suicide rates in North Carolina (NC) by worker characteristics, means of suicide used, and industry between 1992 and 2017.

Methods

Fatal workplace suicides were identified from records of the NC Office of the Chief Medical Examiner system and the NC death certificate. Sex, age, race, ethnicity, class of worker, manner of death, and industry were abstracted. Crude and age‐standardized homicide rates were calculated as the number of suicides that occurred at work divided by an estimate of worker‐years (w‐y). Rate ratios and 95% confidence intervals (CIs) were calculated, and trends over calendar time for fatal workplace suicides were examined overall and by industry.

Results

81 suicides over 109,464,430 w‐y were observed. Increased rates were observed in workers who were male, self‐employed, and 65+ years old. Firearms were the most common means of death (63%) followed by hanging (16%). Gas service station workers experienced the highest fatal occupational suicide rate, 11.5 times (95% CI: 3.62–36.33) the overall fatal workplace suicide rate, followed by Justice, Public Order, and Safety workers at 3.23 times the overall rate (95% CI: 1.31–7.97).

Conclusion

Our findings identify industries and worker demographics that were vulnerable to workplace suicides. Targeted and tailored mitigation strategies for vulnerable industries and workers are recommended.
The National Institutes of Health INvestigation of Co‐occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project: Accelerating research discoveries for people with Down syndrome across the lifespan
Authors: Bardhan Sujata , Li Huiqing , Tarver Erika , Schramm Charlene , Brown Marishka , Garcia Linda , Schwartz Bryanna , Mazzucco Anna , Natarajan Nikila , Walsh Elizabeth , Ryan Laurie , Pearson Gail , Parisi Melissa A.
Published: January 2024

The National Institutes of Health (NIH) has a long‐standing history of support for research in Down syndrome (DS). In response to a 2018 congressional directive for a trans‐NIH initiative to address medical issues in DS, NIH launched the INCLUDE Project (INvestigation of Co‐occurring conditions across the Lifespan to Understand Down syndromE). Reflecting the three INCLUDE components of basic science research, cohort development, and clinical trials, the Project has published funding opportunities to address conditions such as immune disorders and Alzheimer's disease. Due to a steady expansion in dedicated funding over its first 5 years, INCLUDE has invested $258 M in over 250 new research projects. INCLUDE also supports training initiatives to expand the number and diversity of investigators studying DS. NIH has funded an INCLUDE Data Coordinating Center that is collecting de‐identified clinical information and multi‐omics data from research participants for broad data sharing and secondary analyses. Through the DS‐Connect® registry, INCLUDE investigators can access recruitment support. The INCLUDE Research Plan articulates research goals for the program, with an emphasis on diversity of research participants and investigators. Finally, a new Cohort Development Program is poised to increase the impact of the INCLUDE Project by recruiting a large DS cohort across the lifespan.
Mentorship and professional growth for conservationists in primate‐range countries
Authors: Atsalis Sylvia , Gravenberch Marlene , Norconk Marilyn A.
Published: January 2024

Highlights

By providing mentorship and by enhancing professional development skills, primatologists can help to build the professional capacity of emerging conservationists. Actions can be adjusted to specific cultural contexts and interwoven into teaching and research programs.

Sharing stories about pivotal career moments creates closer connections with mentees and helps to stimulate dialogue on issues of concern.

Experiential and networking opportunities assist to broaden the professional perspectives of students and young professionals poised for conservation leadership.
Male‐biased stone tool use by wild white‐faced capuchins (Cebus capucinus imitator)
Authors: Goldsborough Zoë , Crofoot Margaret C. , Barrett Brendan J.
Published: January 2024

Tool‐using primates often show sex differences in both the frequency and efficiency of tool use. In species with sex‐biased dispersal, such within‐group variation likely shapes patterns of cultural transmission of tool‐use traditions between groups. On the Panamanian islands of Jicarón and Coiba, a population of white‐faced capuchins (Cebus capucinus imitator)—some of which engage in habitual stone tool use—provide an opportunity to test hypotheses about why such sex‐biases arise. On Jicarón, we have only observed males engaging in stone tool use, whereas on Coiba, both sexes are known to use tools. Using 5 years of camera trap data, we provide evidence that this variation likely reflects a sex difference in tool use rather than a sampling artifact, and then test hypotheses about the factors driving this pattern. Differences in physical ability or risk‐aversion, and competition over access to anvils do not account for the sex‐differences in tool‐use we observe. Our data show that adult females are physically capable of stone tool use: adult females on Coiba and juveniles on Jicarón smaller than adult females regularly engage in tool use. Females also have ample opportunity to use tools: the sexes are equally terrestrial, and competition over anvils is low. Finally, females rarely scrounge on left‐over food items either during or after tool‐using events, suggesting they are not being provisioned by males. Although it remains unclear why adult white‐faced capuchin females on Jicarón do not use stone‐tools, our results illustrate that such sex biases in socially learned behaviors can arise even in the absence of obvious physical, environmental, and social constraints. This suggests that a much more nuanced understanding of the differences in social structure, diet, and dispersal patterns are needed to explain why sex‐biases in tool use arise in some populations but not in others.
Harmonizing Enzyme‐like Cofactors to Boost Nanozyme Catalysis
Authors: Wu Yu , Zhong Hong , Xu Weiqing , Su Rina , Qin Ying , Qiu Yiwei , Zheng Lirong , Gu Wenling , Hu Liuyong , Lv Fan , Zhang Shipeng , Beckman Scott P. , Lin Yuehe , Zhu Chengzhou , Guo Shaojun
Published: January 2024

Engineering isolated metal sites resembling the primary coordination sphere of metallocofactors enables atomically dispersed materials as promising nanozymes. However, most existing nanozymes primarily focus on replicating specific metallocofactors while neglecting other supporting cofactors within active pockets, leading to reduced electron transfer (ET) efficiency and thus inferior catalytic performances. Herein, we report a metal–organic framework UiO‐67 nanozyme with atomically dispersed iron sites, which involves multiple tailored enzyme‐like nanocofactors that synergistically drive the ET process for enhanced peroxidase‐like catalysis. Among them, the linker‐coupled atomic iron site plays a critical role in substrate activation, while bare linkers and zirconia nodes facilitate the ET efficiency of intermediates. The synergy of three nanocofactors results in a 4.29‐fold enhancement compared with the single effort of isolated metal site‐based nanocofactor, holding promise in immunoassay for sensitive detection of chlorpyrifos. This finding opens a new way for designing high‐performance nanozymes by harmonizing various nanocofactors at the atomic and molecular scale.
Photo‐Assisted Li‐N2 Batteries with Enhanced Nitrogen Fixation and Energy Conversion
Authors: Li Jian‐You , Du Xing‐Yuan , Wang Xiao‐Xue , Yuan Xin‐Yuan , Guan De‐Hui , Xu Ji‐Jing
Published: January 2024

Li‐N2 batteries have received widespread attention for their potential to integrate N2 fixation, energy storage, and conversion. However, because of the low activity and poor stability of cathode catalysts, the electrochemical performance of Li‐N2 batteries is suboptimal, and their electrochemical reversibility has rarely been proven. In this study, a novel bifunctional photo‐assisted Li‐N2 battery system was established by employing a plasmonic Au nanoparticles (NPs)‐modified defective carbon nitride (Au‐Nv‐C3N4) photocathode. The Au‐Nv‐C3N4 exhibits strong light‐harvesting, N2 adsorption, and N2 activation abilities, and the photogenerated electrons and hot electrons are remarkably beneficial for accelerating the discharge and charge reaction kinetics. These advantages enable the photo‐assisted Li‐N2 battery to achieve a low overpotential of 1.32 V, which is the lowest overpotential reported to date, as well as superior rate capability and prolonged cycle stability (≈500 h). Remarkably, a combination of theoretical and experimental results demonstrates the high reversibility of the photo‐assisted Li‐N2 battery. The proposed novel strategy for developing efficient cathode catalysts and fabricating photo‐assisted battery systems breaks through the overpotential bottleneck of Li‐N2 batteries, providing important insights into the mechanism underlying N2 fixation and storage.
Zinc selenide quantum dots as fluorescent labels for biomedical imaging
Authors: D. S. Ivan Jebakumar , D. S. Jenison
Published: January 2024

We, herein, report a facile green synthetic route for the gram‐scale synthesis of high‐quality thiol‐derivatized zinc selenide quantum dots (QDs) using selenourea as the source of selenium at a relatively low temperature. The one‐pot synthesis of colloidal dots has been achieved by selenizing zinc (II) acetate in a non‐coordinating solvent medium. The structural, microstructural, optical, thermal, textural and electronic properties of the as‐synthesized monodisperse ZnSe dots have been investigated in detail. We attribute the observed green emission from the dots to the donor‐acceptor pair (DAP) recombination of photoexcited charge carriers. All the findings of the investigation indicate that ZnSe QDs hold great promise as a nanoscale emissive probe to unveil cellular dynamics beyond the capabilities of conventional imaging techniques.
Evolution of surface microstructure of Re‐Al‐Ni‐Au based ohmic contacts on n‐type GaN
Authors: Shah Amit P. , Chalke Bhagyashree A. , Parmar Jayesh B. , Ghag Manish B. , Bhattacharya Arnab
Published: January 2024

Recently, rhenium (Re) based ohmic contacts to GaN have been studied for their low resistivity, smooth surface morphology, and sharp edge acuity at low annealing temperatures. In this work, we discuss the evolution of surface microstructures for Re‐Al‐Ni‐Au ohmic contacts on n‐GaN as a function of Re layer thickness and annealing temperature. For all Re thicknesses, the Al and Ni segregate into agglomerates that increase in size with increasing annealing temperature. These agglomerates are surrounded by Al‐Au films. Along with the underlying Re layer, they form different crystallographic phases of Re‐Al‐Ni, Al6Re, AlAu2, and Al2Au5. This, along with the formation of Re‐N phases at the metal‐semiconductor interface leads to low resistivity ohmic contacts on n‐GaN. Investigating the evolution of the contact microstructure is an important step in understanding the behavior of the Re‐based ohmic contact system.
A DNA‐based evaluation of North American river otter diet with respect to fishes: Implications for the conservation of aquatic predators and their prey
Authors: Heenkenda Erangi J. , Heniff Ashlyn C. , Fisher Brant E. , Albers Geriann , DeWoody J. Andrew
Published: January 2024

The North American river otter Lontra canadensis was once widespread in North America but became extinct in the State of Indiana owing to habitat losses and unregulated trapping. However, following reintroduction, the population has expanded markedly since 1995, representing a notable conservation success story.

The recent population growth has led to conflict with recreational angling groups who perceive otters as competitors. To investigate the extent of this competition, a DNA‐based study was conducted to determine whether material from the stomachs of trapper‐harvested otters could be used to identify fish prey species they had eaten.

Representative specimens from 33 wild fish species were used as positive controls for DNA assays of otter prey. Mitochondrial DNA barcoding sequences generated from each fish species were used to develop a piscine barcoding assay to identify otter prey species.

Fourteen otter carcasses were dissected, and multiple independent DNA extractions and mitochondrial sequencing reactions were performed on the prey bolus from each stomach. The sequences were analysed bioinformatically for taxonomic assignment to prey species.

DNA evidence of nearly two dozen fish species, including species of recreational (e.g. bass) or conservation interest (darters) was found in the stomach material.

This approach could help to determine the presence of prey species in otter diets, including those fish of conservation concern. That, in turn, would help to determine the best management options for conserving both otters and fish.