bluuebunny/crossref_metadata_2025 huggingface dataset:
An efficient polar cubic equation of state for predictive modeling of phase behavior and critical phenomena of mixtures
Authors: Abutaqiya Mohammed I. L. , Marshall Bennett D.
Published: April 2024

A polar cubic equation of state (EOS) is developed by incorporating the dipolar theory of Jog and Chapman into the Soave‐Redlich‐Kwong (SRK) EOS. We propose simplifying assumptions in the dipolar term of Jog and Chapman to reduce the double and triple sums in the theory to single sums. The simplified version of the dipolar theory can significantly improve computational speed and can be used with either Cubic EOS or SAFT‐based EOS. The proposed model, which we call Simplified Polar SRK (SP‐SRK), is parametrized in a similar fashion to classical cubic EOS to exactly reproduce , and will self‐consistently reduce to the base SRK EOS in the absence of polar interactions. Binary VLE data with a non‐polar reference hydrocarbon is used to extract the polarity of the respective functional group. The model shows superior performance in capturing the phase behavior of polar mixtures compared to the base SRK.
Genomics of severe and treatment‐resistant obsessive–compulsive disorder treated with deep brain stimulation: A preliminary investigation
Authors: Chen Long Long , Naesström Matilda , Halvorsen Matthew , Fytagoridis Anders , Crowley Stephanie B. , Mataix‐Cols David , Rück Christian , Crowley James J. , Pascal Diana
Published: April 2024

Individuals with severe and treatment‐resistant obsessive‐compulsive disorder (trOCD) represent a small but severely disabled group of patients. Since trOCD cases eligible for deep brain stimulation (DBS) probably comprise the most severe end of the OCD spectrum, we hypothesize that they may be more likely to have a strong genetic contribution to their disorder. Therefore, while the worldwide population of DBS‐treated cases may be small (~300), screening these individuals with modern genomic methods may accelerate gene discovery in OCD. As such, we have begun to collect DNA from trOCD cases who qualify for DBS, and here we report results from whole exome sequencing and microarray genotyping of our first five cases. All participants had previously received DBS in the bed nucleus of stria terminalis (BNST), with two patients responding to the surgery and one showing a partial response. Our analyses focused on gene‐disruptive rare variants (GDRVs; rare, predicted‐deleterious single‐nucleotide variants or copy number variants overlapping protein‐coding genes). Three of the five cases carried a GDRV, including a missense variant in the ion transporter domain of KCNB1, a deletion at 15q11.2, and a duplication at 15q26.1. The KCNB1 variant (hg19 chr20‐47991077‐C‐T, NM_004975.3:c.1020G>A, p.Met340Ile) causes substitution of methionine for isoleucine in the trans‐membrane region of neuronal potassium voltage‐gated ion channel KV2.1. This KCNB1 substitution (Met340Ile) is located in a highly constrained region of the protein where other rare missense variants have previously been associated with neurodevelopmental disorders. The patient carrying the Met340Ile variant responded to DBS, which suggests that genetic factors could potentially be predictors of treatment response in DBS for OCD. In sum, we have established a protocol for recruiting and genomically characterizing trOCD cases. Preliminary results suggest that this will be an informative strategy for finding risk genes in OCD.
Usefulness of the Yokohama Advanced Cardiopulmonary Help Team in patients with acute respiratory distress syndrome
Authors: Utada Shusuke , Taniguchi Hayato , Honzawa Hiroshi , Takeda Tomoaki , Abe Takeru , Takeuchi Ichiro
Published: April 2024

Aim

To evaluate whether establishing an extracorporeal membrane oxygenation (ECMO) specialist team, termed the Yokohama Advanced Cardiopulmonary Help Team (YACHT), affected the outcomes and centralization of patients requiring ECMO in Yokohama‐Yokosuka regions.

Methods

This retrospective observational study included patients aged ≥18 years and treated with venovenous‐ECMO for severe acute respiratory distress syndrome (ARDS) from 2014 to 2023. The primary outcome was intensive care unit (ICU) mortality. The secondary outcomes included ICU‐, mechanical ventilator‐, and ECMO‐free days and complications during the first 28 days.

Results

This study included 46 (12 without‐ and 34 with‐YACHT) patients. Among with‐YACHT patients, 24 were transferred to our hospital from other hospitals, 14 were assessed by dispatched ECMO physicians, and 9 were transferred after ECMO introduction. No without‐YACHT patients were transferred from other hospitals. With‐YACHT patients experienced coronavirus disease 2019‐associated respiratory failure more frequently (0 vs. 27, p < 0.001) and had higher Acute Physiology and Chronic Health Evaluation II scores (19 vs. 24, p = 0.037) and lower Respiratory Extracorporeal Membrane Oxygenation Survival Prediction scores (4 vs. 2, p = 0.021). ICU mortality was not significantly different between the groups (2 vs. 4, p = 0.67). ICU‐ (14 vs. 9, p = 0.10), ventilator‐ (11 vs. 5, p = 0.01), and ECMO‐free days (20 vs. 14, p = 0.038) were higher before YACHT establishment. The incidences of complications were not significantly different between the groups.

Conclusions

Mortality was not significantly different pre‐ and post‐YACHT establishment; however, it helped promote regionalization and centralization in Yokohama‐Yokosuka areas. We will collect more cases to demonstrate YACHT's usefulness.
Adhesion Peptide‐Functionalized Biobased Microgels for Controlled Delivery of Pesticides
Authors: Yayci Abdulkadir , Sassmann Tim , Boes Alexander , Jakob Felix , Töpel Alexander , Loreth Anne , Rauch Carolin , Pich Andrij , Schwaneberg Ulrich
Published: April 2024

Widespread use of plant protection agents in agriculture is a major cause of pollution. Apart from active ingredients, the environmental impact of auxiliary synthetic polymers should be minimized if they are highly persistent. An alternative to synthetic polymers is the use of natural polysaccharides, which are abundant and biodegradable. In this study, we explore pectin microgels functionalized with anchor peptides (P‐MAPs) to be used as an alternative biobased pesticide delivery system. Using copper as the active ingredient, P‐MAPs effectively prevented infection of grapevine plants with downy mildew under semi‐field conditions on par with commercial copper pesticides. By using anchor peptides, the microgels tightly bind to the leaf surface, exhibiting excellent rain fastness and prolonged fungicidal activity. Finally, P‐MAPs are shown to be easily degradable by enzymes found in nature, demonstrating their negligible long‐term impact on the environment.
Cathodic Deposition‐Assisted Synthesis of Thin Glass MOF Films for High‐Performance Gas Separations
Authors: Xie Sijie , Tan Xiaoyu , Xue Zhenhong , Geysens Pieter , Pan Hui , Guo Wei , Zhou Zhenyu , Zhang Xuan , Vankelecom Ivo F. J. , Fransaer Jan
Published: April 2024

Glass metal–organic framework (MOF) films can be fabricated from their crystalline counterparts through a melt‐quenching process and are prospective candidates for gas separation because of the elimination of the grain boundaries in crystalline MOF films. However, current techniques are limited to producing glass MOF films with a thickness of tens of micrometers, which leads to ultralow gas permeances. Here, we report a novel cathodic deposition‐assisted synthesis of glass ZIF‐62 films with a thickness as low as ~1 μm. Electrochemical analyses and deposition experiments suggest that the cathodic deposition can lead to pure crystalline ZIF‐62 films with a controllable thickness of ~2 μm to ~15 μm. Accordingly, glass ZIF‐62 films with a thickness of ~1 μm to ~10 μm can be obtained after a thermal treatment. The fabricated defect‐free glass ZIF‐62 film measuring 2 μm in thickness shows a remarkable CO2/N2 and CO2/CH4 selectivity of 31.4 and 33.4, respectively, with a CO2 permeance which is over 30 times higher than the best‐performing glass ZIF‐62 films in literature.
Polyfluorinated Organic Diammonium Induced Lead Iodide Arrangement for Efficient Two‐Step‐Processed Perovskite Solar Cells
Authors: Liu Yang , Liu Qiuju , Lu Yusong , Fu Jianfei , Wu Jifeng , Tian Qingyong , Fan Bin , Zhang Yan , Bai Hua , Wang Hai‐Qiao
Published: April 2024

The inefficient conversion of lead iodide to perovskite has become one of the major challenges in further improving the performance of perovskite solar cells fabricated by the two‐step method. Herein, the discontinuous lead iodide layer realized by introduction of a polyfluorinated organic diammonium salt, octafluoro‐([1,1′‐biphenyl]‐4,4′‐diyl)‐dimethanaminium (OFPP) iodide which does not form low‐dimensional perovskites, can enable the satisfactory conversion of lead iodide into perovskite, leading to meliorated crystallinity and enlarged grains in the OFPP modulated perovskite (OFPP‐PVK) film. Combined with the effective defect passivation, the OFPP‐PVK films show enhanced charge mobility and suppressed charge recombination. Accordingly, the OFPP‐based perovskite solar cells exhibit a champion efficiency of 24.76 % with better device stability. Moreover, a superior efficiency of 21.04 % was achieved in a large‐area perovskite module (100 cm2). Our work provides a unique insight into the function of organic diammonium additive in boosting photovoltaic performance.
Formation of Supernarrow Borophene Nanoribbons
Authors: Wang Haochen , Ding Pengcheng , Xia Guang‐Jie , Zhao Xiangyun , E Wenlong , Yu Miao , Ma Zhibo , Wang Yang‐Gang , Wang Lai‐Sheng , Li Jun , Yang Xueming
Published: April 2024

Borophenes have sparked considerable interest owing to their fascinating physical characteristics and diverse polymorphism. However, borophene nanoribbons (BNRs) with widths less than 2 nm have not been achieved. Herein, we report the experimental realization of supernarrow BNRs. Combining scanning tunneling microscopy imaging with density functional theory modeling and ab initio molecular dynamics simulations, we demonstrate that, under the applied growth conditions, boron atoms can penetrate the outermost layer of Au(111) and form BNRs composed of a pair of zigzag (2,2) boron rows. The BNRs have a width self‐contained to ∼1 nm and dipoles at the edges to keep them separated. They are embedded in the outermost Au layer and shielded on top by the evacuated Au atoms, free of the need for post‐passivation. Scanning tunneling spectroscopy reveals distinct edge states, primarily attributed to the localized spin at the BNRs’ zigzag edges. This work adds a new member to the boron material family and introduces a new physical feature to borophenes.
Enrooted‐Type Metal‐Support Interaction Boosting Oxygen Evolution Reaction in Acidic Media
Authors: Wang Wenjuan , Li Cheng , Zhou Chuan , Xiao Xin , Li Fayan , Huang Ning‐Yu , Li Lei , Gu Meng , Xu Qiang
Published: April 2024

Supported metal catalysts with appropriate metal‐support interactions (MSIs) hold a great promise for heterogeneous catalysis. However, ensuring tight immobilization of metal clusters/nanoparticles on the support while maximizing the exposure of surface active sites remains a huge challenge. Herein, we report an Ir/WO3 catalyst with a new enrooted‐type MSI in which Ir clusters are, unprecedentedly, atomically enrooted into the WO3 lattice. The enrooted Ir atoms decrease the electron density of the constructed interface compared to the adhered (root‐free) type, thereby achieving appropriate adsorption toward oxygen intermediates, ultimately leading to high activity and stability for oxygen evolution in acidic media. Importantly, this work provides a new enrooted‐type supported metal catalyst, which endows suitable MSI and maximizes the exposure of surface active sites in contrast to the conventional adhered, embedded, and encapsulated types.
Biological autoluminescence enables effective monitoring of yeast cell electroporation
Authors: Bereta Martin , Teplan Michal , Zakar Tomáš , Vuviet Hoang , Cifra Michal , Chafai Djamel Eddine
Published: April 2024

The application of pulsed electric fields (PEFs) is becoming a promising tool for application in biotechnology, and the food industry. However, real‐time monitoring of the efficiency of PEF treatment conditions is challenging, especially at the industrial scale and in continuous production conditions.  To overcome this challenge, we have developed a straightforward setup capable of real‐time detection of yeast biological autoluminescence (BAL) during pulsing. Saccharomyces cerevisiae culture was exposed to 8 pulses of 100 µs width with electric field strength magnitude 2–7 kV cm−1. To assess the sensitivity of our method in detecting yeast electroporation, we conducted a comparison with established methods including impedance measurements, propidium iodide uptake, cell growth assay, and fluorescence microscopy. Our results demonstrate that yeast electroporation can be instantaneously monitored during pulsing, making it highly suitable for industrial applications. Furthermore, the simplicity of our setup facilitates its integration into continuous liquid flow systems. Additionally, we have established quantitative indicators based on a thorough statistical analysis of the data that can be implemented through a dedicated machine interface, providing efficiency indicators for analysis.
Phase separation methods for protein purification: A meta‐analysis of purification performance and cost‐effectiveness
Authors: Decker John S. , Yano Utsuki , Melgar Romel Menacho , Lynch Michael D.
Published: April 2024

Protein purifications based on phase separations (e.g., precipitation and liquid‐liquid extraction) have seen little adoption in commercial protein drug production. To identify barriers, we analyzed the purification performance and economics of 290 phase separation purifications from 168 publications. First, we found that studies using Design of Experiments for optimization achieved significantly greater mean yield and host cell protein log10 removal values than those optimizing one factor at a time (11.5% and 53% increases, respectively). Second, by modeling each reported purification at scales from 10 to 10,000 kg product/year and comparing its cost‐effectiveness versus chromatography, we found that cost‐effectiveness depends strongly on scale: the fraction of phase separations predicted to be cost‐effective at the 10, 100, and 1000 kg/year scales was 8%, 15%, and 43%, respectively. Total cost per unit product depends inversely on input purity, with phase separation being cheaper than chromatography at the 100 kg/year scale in 100% of cases where input purity was ≤ 1%, compared to about 25% of cases in the dataset as a whole. Finally, we identified a simple factor that strongly predicts phase separation process costs: the mass ratio of reagents versus purified product (the “direct materials usage rate”), which explains up to 58% of variation in cost per unit of purified product among all 290 reports, and up to 98% of variation within particular types of phase separation.
Survival and safety analysis of COVID‐19 vaccine in Chinese patients with non‐small cell lung cancer
Authors: Xu Wei , Zhao Jing , Luan Fang , Zhang Zhizhao , Liu Lei , Zhao Hui , Feng Bin , Fu Guobin
Published: April 2024

Background

Severe acute respiratory syndrome coronavirus 2 disease (COVID‐19) has caused a worldwide challenging and threatening pandemic. We aimed to assess the safety and efficacy of the COVID‐19 vaccines in Non‐Small Cell Lung Cancer (NSCLC) patients.

Methods

Patient self‐reported adverse events related to vaccines were recorded by follow‐up through a uniform questionnaire. Survival analysis was performed by Kaplan–Meier method. A multivariate analysis was performed by the Cox proportional hazard regression model to determine the effect of each variable on the survival of lung cancer patients.

Results

A total of 860 patients with NSCLC on treatment were enrolled. Mean age was 57 years in patients with early stage group and 62 years in advanced stage group. The vaccination rate was 71.11% for early‐stage patients and 19.48% for advanced‐stage patients; most of them (86.5%) received the COVID‐19 inactivated virus (Vero cell) vaccine (Coronavac; Sinovac). The most common systemic adverse reaction was weakness. The main reason for vaccine refusal in those unvaccinated patients was concern about the safety of vaccination in the presence of a tumor and undergoing treatment (56.9% and 53.4%). The 1‐year disease‐free survival (DFS) rate was 100% for vaccinated and 97.4% for unvaccinated early‐stage patients. Then we compared the progression‐free survival (PFS) of vaccinated (median PFS 9.0 months) and unvaccinated (median PFS 7.0 months) advanced stage patients (p = 0.815). Advanced NSCLC patients continued to be divided into groups receiving radio‐chemotherapy, immunotherapy, and targeted therapy, with no statistical difference in PFS between the groups (p > 0.05). The median overall survival (OS) of vaccinated patients was 20.5 months, and that of unvaccinated patients was 19.0 months (p = 0.478) in advanced NSCLC patients.

Conclusions

COVID‐19 vaccination is safe for Chinese NSCLC patients actively receiving different antitumor treatments without increasing the incidence of adverse reactions, and vaccination does not affect cancer patient survival.
Disparities in incidence and survival for patients with Ewing sarcoma in Florida
Authors: Dhir Aditi , Rahul Rachna , Liu Qinran , Pham Dan , Kronenfeld Rachel , Koru‐Sengul Tulay , Pinheiro Paulo S.
Published: April 2024

Background

Ewing sarcoma (ES) is a malignant bone tumor most commonly affecting non‐Hispanic White (NHW) adolescent males, though recognition among Hispanic individuals is rising. Prior population‐based studies in the United States (US), utilizing Surveillance, Epidemiology, and End Results (SEER) have shown higher all‐cause mortality among White Hispanics, Blacks, and those of low socioeconomic status (SES). Florida is not part of SEER but is home to unique Hispanic populations including Cubans, Puerto Ricans, South Americans that contrasts with the Mexican Hispanic majority in other US states. This study aimed to assess racial/ethnic disparities on incidence and survival outcomes among this diverse Florida patient population.

Methodology

Our study examined all patients diagnosed with osseous ES (2005–2018) in Florida (n = 411) based on the state's population‐based cancer registry dataset. Florida Age‐adjusted Incidence Rates (AAIRs) were computed by sex and race‐ethnicity and compared to the equivalent populations in SEER. Cause‐specific survival disparities among Florida patients were examined using Kaplan–Meier analysis. Univariable and multivariable analyses using Cox regression were performed for race/ethnicity, with adjustment for age, sex, year of diagnosis, site of disease, staging, SES, and insurance type.

Results

There was a significantly higher incidence of osseous ES in Florida Hispanic males (AAIR 2.6/1,000,000); (95% CI: 2.0–3.2 per 1,000,000; n = 84) compared to the SEER Hispanic males (AAIR 1.2/1,000,000;1.1–1.4 per 1,000,000; n = 382). Older age, distant metastasis, lack of chemotherapy or surgical resection were statistically significant determinants of poor survival while SES, insurance status and race‐ethnicity were not. However, among nonmetastatic ES, Florida Hispanics had an increased risk of death compared to Florida NHW (adjusted Hazard Ratio 2.32; 95%CI: 1.20–4.46; p = 0.012).

Conclusions

Florida Hispanic males have a higher‐than‐expected incidence of osseous ES compared to the US. Hispanics of both sexes show remarkably worse survival for nonmetastatic disease compared to NHW. This disparity is likely multifactorial and requires further in‐depth studies.
Seasonal and Circadian Variation of Non‐Volatile Metabolites in Lippia alba Leaves
Authors: Rocha Girlane Oliveira , Scabini Caroline , da Silva Oliveira Jayne Ferreira , Neres Oliveira Déborah , Carvalho Mota Luise , Novais Almeida Neves Brenda , Menezes dos Santos Amanda , Mendes de Souza Flávio , Santos de Araújo Urias , Moreira Bruno Oliveira , Prates de Almeida Maiara , Amaral Juliano Geraldo , David Jorge Maurício , Ferraz Gomes Angélica
Published: April 2024

The present study describes the seasonal and circadian variations of the major compounds from Lippia alba leaves. SPSS was used to identify, quantify, and associate the variations in the secondary metabolites of this species through HPLC/DAD analysis of the leaves hydroethanolic extracts of six selected L. alba specimens. For the circadian study, the samples were collected at four different daily hours in each year‘s season. For the seasonal study, the samples were collected monthly from the same individuals for two consecutive years (2018 and 2019). These samples were analyzed and quantified using a validated HPLC method for flavonoids, iridoids, and phenyl ethanoid glycoside. Mussaenoside, acteoside, and tricin‐7‐O‐diglucuronide showed a moderate positive correlation between their biosynthesis and the precipitation index, while epi‐loganin had a moderate negative correlation. Acteoside showed a moderate positive correlation between the minimum registered temperature and its production. Compared with previous studies, a drastic reduction (about 95 %) in the production of tricin‐7‐O‐diglucuronide compared with previous study and this difference could be attributed to the plant‘s aging. Thus, the data demonstrated that lower temperatures and high rainfall could favor the production of the major L. alba active compounds (acteoside and tricin‐7‐O‐diglucuronide) and that older plants harm their production.
Polymeric Binders Used in Lithium Ion Batteries: Actualities, Strategies and Trends
Authors: Chen Bin , Zhang Zhe , Xiao Min , Wang Shuanjin , Huang Sheng , Han Dongmei , Meng Yuezhong
Published: April 2024

Polymeric binders account for only a small part of the electrodes in lithium‐ion batteries, but contribute an important role of adhesion and cohesion in the electrodes during charge/discharge processes to maintain the integrity of the electrode structure. Therefore, polymeric binders have become one of the key materials to improve the charge/discharge properties of lithium‐ion batteries. Qualified polymer binders should not only require good bond strength, mechanical properties, conductivity, chemical functionality and processing performance, but also be environmentally friendly and low cost. The existing commercial polymeric binders cannot meet all the above requirements at the same time. This is a hot research area that researchers are keen to focus on, and it is hoped that through structural design, the matching of functional groups can meet the requirements of high‐capacity lithium‐ion batteries with long cycle life. Focusing on the structural design of polymer binders, the mechanism of interaction with electrode materials, and the functional properties of polymer binders, this review summarizes the polymer binders used in the cathode and anode in recent years. It could expect that this review can inspire a deep consideration on these critical issues, paving new pathways to improve comprehensive performance of polymer binders.
Role of catalyst topology in methanol synthesis
Authors: Hastadi Kemal F. , Shah Milinkumar T. , Bhatelia Tejas , Sun Biao , Pareek Vishnu K.
Published: April 2024

Methanol synthesis is carried out in a catalytic, packed bed reactor, where the shape and size of catalyst play a critical role in dictating overall reactor performance. In the current study, the effect of five different catalyst shapes including cylindrical, ring, trilobe, wagon wheel, and spherical on the reactor performance was investigated by conducting particle‐scale computational fluid dynamics (CFD) simulations. The predictions of pressure drop, velocity, temperature, reactant distribution and product yield were analyzed. When the performance of the simulated shapes was compared at the same tube Reynolds number of 50,000, internally contoured shapes (wagon wheel and ring) resulted in 40% higher pressure drops due to the tortuous flow path. However, the shape with internal void provided access for the reactant to reach the internal part of catalyst, resulting in higher yield produced per volume of catalyst. The wagon wheel shape produced 15% and 5% more yield per volume against the cylindrical shape and trilobe, respectively. The performance of the wagon wheel can be attributed to the lower diffusion limitation due to higher surface area available for reactant to penetrate the internal part of the catalyst.
Decolorization of anthraquinone dye by Brevibacillus laterosporus R81 via polysaccharides excreted
Authors: Zhang Yanzhou , Tang Xingyao , Wu Limeng , Shen Min , Kang Yijun
Published: April 2024

The aim of this research was to assess the efficacy of different microbial strains in the decolorization of anthraquinone dyes. Strain R81 was obtained from a textile company's wastewater discharge for its remarkable ability to decolorize reactive blue 19 (RB19). By employing physiological and biochemical analyses, along with 16S rRNA gene sequencing, strain R81 was determined to be Brevibacillus laterosporus. After optimization, the decolorization rate achieved a peak of 86.24% over a 48‐h timeframe, utilizing an initial dye concentration of 100 mg L–1. The decolorization capacity of strain R81 was observed to be impeded by heightened levels of salt and temperature in culture solutions, yet remained unaltered when R81 cells were directly introduced into dye solutions. Furthermore, cells that were induced through prior cultivation in a medium containing RB19 demonstrated enhanced efficacy in decolorization compared to noninduced cells. Subsequent analysis indicated that the development of biofilms and the synthesis of polysaccharides by strain R81 were augmented in a concentration‐dependent fashion by RB19. Nevertheless, the decolorization efficacy of R81 was impeded by the existence of sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB), both of which possess the capacity to eliminate polysaccharides. The decolorization capabilities were reinstated by the SDS or CTAB eluent containing polysaccharides, suggesting a reliance on the presence of polysaccharides. The employment of stepwise diethylaminoethyl (DEAE)‐cellulose chromatography and decolorization experiments elucidated the importance of a specific polysaccharide in the decolorization process. This study proposes a bacteria‐derived polysaccharide as a promising remedy for treating dyeing wastewater contaminated with anthraquinones.
Developing a Novel Enzalutamide‐Resistant Prostate Cancer Model via AR F877L Mutation in LNCaP Cells
Authors: Wang Ruifeng , Ma Shuhua , Xu Nengwei , Gan Yumiao , Li Pengya , Zhang Jingying , Zhang Zhixiang , Gu Qingyang , Xiang Jian
Published: April 2024

Prostate cancer is a leading diagnosis and major cause of cancer‐related deaths in men worldwide. As a typical hormone‐responsive disease, prostate cancer is commonly managed with androgen deprivation therapy (ADT) to curb its progression and potential metastasis. Unfortunately, progression to castration‐resistant prostate cancer (CRPC), a notably more aggressive phase of the disease, occurs within a timeframe of 2‐3 years following ADT. Enzalutamide, a recognized androgen receptor (AR) antagonist, has been employed as a standard of care for men with metastatic castration‐resistant prostate cancer (mCRPC) since it was first approved in 2012, due to its ability to prolong survival. However, scientific evidence suggests that sustained treatment with AR antagonists may induce acquired AR mutations or splice variants, such as AR F877L, T878A, and H875Y, leading to drug resistance and thereby diminishing the therapeutic efficacy of these agents. Thus, the establishment of prostate cancer models incorporating these particular mutations is essential for developing new therapeutic strategies to overcome such resistance and evaluate the efficacy of next‐generation AR‐targeting drugs. We have developed a CRISPR (clustered regularly interspaced short palindromic repeats)‐based knock‐in technology to introduce an additional F877L mutation in AR into the human prostate cell line LNCaP. This article provides comprehensive descriptions of the methodologies for cellular gene editing and establishment of an in vivo model. Using these methods, we successfully identified an enzalutamide‐resistant phenotype in both in vitro and in vivo models. We also assessed the efficacy of target protein degraders (TPDs), such as ARV‐110 and ARV‐667, in both models, and the corresponding validation data are also included here. © 2024 Wiley Periodicals LLC.

Basic Protocol 1: Generation of AR F877L‐mutated LNCaP cell line using CRISPR technology

Basic Protocol 2: Validation of drug resistance in AR F877L‐mutated LNCaP cell line using the 2D CTG assay

Support Protocol: Testing of sgRNA efficiency in HEK 293 cells

Basic Protocol 3: Validation of drug resistance in AR F877L‐mutated LNCaP cell line in vivo
The impact of ISO 45001 on firms' performance: An empirical analysis
Authors: Podrecca Matteo , Molinaro Margherita , Sartor Marco , Orzes Guido
Published: April 2024

The aim of this study is to shed light on the relationship between ISO 45001 adoption and firm performance. To explore the issue, we conduct an event study and a weighted least squares regression on a dataset of 157 publicly listed companies – operating in various countries and sectors – that have given public announcement of the attainment of the ISO 45001 certification. The results show that, when compared to non‐adopters, ISO 45001‐certified companies display better performance in terms of productivity and profitability, while no significant differences emerge for sales. The effects of ISO 45001 adoption are significantly influenced by industry‐ and company‐related contextual factors. The study contributes to the academic literature by developing the first large‐scale empirical investigation on the performance implications of ISO 45001. Furthermore, it informs managers that by ensuring healthy and safe workplaces companies can also achieve higher financial performance.
Triazine‐Carbazole‐Based Covalent Organic Frameworks as Efficient Heterogeneous Photocatalysts for the Oxidation of N‐aryltetrahydroisoquinolines
Authors: Wang Wen , Meng Fanyu , Bai Yuhongxu , Lu Yongchao , Yang Qingru , Feng Jing , Su Qing , Ren Hao , Wu Qiaolin
Published: April 2024

Covalent organic frameworks (COFs) have attracted growing interests as new material platform for a range of applications. In this study, a triazine‐carbazole‐based covalent organic framework (COF‐TCZ) was designed as highly porous material with conjugated donor‐acceptor networks, and feasibly synthesized by the Schiff condensation of 4,4′,4′′‐(1,3,5‐triazine‐2,4,6‐triyl)tr ianiline (TAPB) and 9‐(4‐formylphenyl)‐9H‐carbazole‐3,6‐dicarbaldehyde (CZTA) under the solvothermal condition. Considering the effect of linkage, the imine‐linked COF‐TCZ was further oxidized to obtain an amide‐linked covalent organic framework (COF‐TCZ‐O). The as‐synthesized COFs show high crystallinity, good thermal and chemical stability, and excellent photoactive properties. Two π‐conjugated triazine‐carbazole‐based COFs with tunable linkages are beneficial for light‐harvesting capacity and charge separation efficiency, which are empolyed as photocatalysts for the oxidation reaction of N‐aryltetrahydroisoquinoline. The COFs catalyst systems exhibit the outstanding photocatalytic performance with high conversion, photostability and recyclability. Photoelectrochemical tests were employed to examine the behavior of photogenerated charge carriers in photo‐illumination system. The control experiments provide further insights into the nature of photocatalysis. In addition, the current research also provided a valuable approach for developing photofunctional COFs to meet challenge in achieving the great potential of COFs materials in organic conversion.
Phosphotungstic Acid Clusters Decorated Znln2S4 Nanoflowers as Molecular‐Scale S‐Scheme Heterojunctions for Simultaneous H2 Evolution and Benzyl Alcohol Upgrading
Authors: Wang Weikang , Mei Shaobin , Khan Shahid , Hu Yujue , Sun Lijuan , Qaiser Muhammad Adnan , Zhu Chengzhang , Wang Lele , Liu Qinqin
Published: April 2024

Simultaneous utilization of photogenerated electrons and holes to achieve overall redox reactions is attractive but still far from practical application. The emerging step (S)‐scheme mechanism has proven to be an ideal approach to inhibit charge recombination and supply photoinduced charges with highest redox potentials. Herein, a hierarchical phosphotungstic acid (H3PW12O40, HPW)@Znln2S4 (ZISW) heterojunction was prepared through one‐pot hydrothermal method for simultaneous hydrogen (H2) evolution and benzyl alcohol upgrading. The fabricated HPW‐based heterojunctions indicated much enhanced visible‐light absorption, promoted photogenerated charge transfer and inhibited charge recombination, owing to hierarchical architecture based on visible‐light responsive Znln2S4 microspheres, and S‐scheme charge transfer pathway. The S‐scheme mechanism was further verified by free‐radical trapping electron spin resonance (ESR) spectra. Moreover, the wettability of composite heterojunction was improved by the modification of hydrophilic HPW, contributing to gaining active hydrogen (H+) from water sustainably. The optimal ZISW‐30 heterojunction photocatalyst indicated an enhanced hydrogen evolution rate of 27.59 mmol g−1 h−1 in benzyl alcohol (10 vol. %) solution under full‐spectrum irradiation, along with highest benzaldehyde production rate is 8.32 mmol g−1 h−1. This work provides a promising guideline for incorporating HPW into S‐scheme heterojunctions to achieve efficient overall redox reactions.
Insights from a 31‐year study demonstrate an inverse correlation between recreational activities and red deer fecundity, with bodyweight as a mediator
Authors: Weterings Martijn J. A. , Ebbinge Estella Y. C. , Strijker Beau N. , Spek Gerrit‐Jan , Kuipers Henry J.
Published: April 2024

Human activity is omnipresent in our landscapes. Animals can perceive risk from humans similar to predation risk, which could affect their fitness. We assessed the influence of the relative intensity of recreational activities on the bodyweight and pregnancy rates of red deer (Cervus elaphus) between 1985 and 2015. We hypothesized that stress, as a result of recreational activities, affects the pregnancy rates of red deer directly and indirectly via a reduction in bodyweight. Furthermore, we expected non‐motorized recreational activities to have a larger negative effect on both bodyweight and fecundity, compared to motorized recreational activities. The intensity of recreational activities was recorded through visual observations. We obtained pregnancy data from female red deer that were shot during the regular hunting season. Additionally, age and bodyweight were determined through a post‐mortem examination. We used two Generalized‐Linear‐Mixed Models (GLMM) to test the effect of different types of recreation on (1) pregnancy rates and (2) bodyweight of red deer. Recreation had a direct negative correlation with the fecundity of red deer, with bodyweight, as a mediator as expected. Besides, we found a negative effect of non‐motorized recreation on fecundity and bodyweight and no significant effect of motorized recreation. Our results support the concept of humans as an important stressor affecting wild animal populations at a population level and plead to regulate recreational activities in protected areas that are sensitive. The fear humans induce in large‐bodied herbivores and its consequences for fitness may have strong implications for animal populations.
Cloning, characterization, and evolutionary patterns of KCNQ4 genes in anurans
Authors: Guo Yang , Zhu Yanjun , Shen Shiyuan , Lu Ningning , Zhang Jie , Chen Xiaohong , Chen Zhuo
Published: April 2024

Acoustic communication plays important roles in the survival and reproduction of anurans. The perception and discrimination of conspecific sound signals of anurans were always affected by masking background noise. Previous studies suggested that some frogs evolved the high‐frequency hearing to minimize the low‐frequency noise. However, the molecular mechanisms underlying the high‐frequency hearing in anurans have not been well explored. Here, we cloned and obtained the coding regions of a high‐frequency hearing‐related gene (KCNQ4) from 11 representative anuran species and compared them with orthologous sequences from other four anurans. The sequence characteristics and evolutionary analyses suggested the highly conservation of the KCNQ4 gene in anurans, which supported their functional importance. Branch‐specific analysis showed that KCNQ4 genes were under different evolutionary forces in anurans and most anuran lineages showed a generally strong purifying selection. Intriguingly, one significantly positively selected site was identified in the anuran KCNQ4 gene based on FEL model. Positive selection was also found along the common ancestor of Ranidae and Rhacophoridae as well as the ancestral O. tianmuii based on the branch‐site analysis, and the positively selected sites identified were involved in or near the N‐terminal ion transport and the potassium ion channel functional domain of the KCNQ4 genes. The present study revealed valuable information regarding the KCNQ4 genes in anurans and provided some new insights for the underpinnings of the high‐frequency hearing in frogs.
Insights into the evolution of herbivory from a leaf‐mining fly
Authors: Aguilar Jessica M. , Gloss Andrew D. , Suzuki Hiromu C. , Verster Kirsten I. , Singhal Malvika , Hoff Jordan , Grebenok Robert , Nabity Paul D. , Behmer Spencer T. , Whiteman Noah K.
Published: April 2024

Herbivorous insects and their host plants comprise most known species on Earth. Illuminating how herbivory repeatedly evolved in insects from nonherbivorous lineages is critical to understanding how this biodiversity is created and maintained. We characterized the trophic niche of Scaptomyza flava, a representative of a lineage nested within the Drosophila that transitioned to herbivory ~10–15 million years ago. We used natural history studies to determine whether S. flava is a true herbivore or a cryptic microbe‐feeder, given that the ancestral character state for the family Drosophilidae is likely microbe‐feeding. Specifically, we quantified oviposition substrate choice and larval viability across food types, trophic‐related morphological traits, and nitrogen isotope and sterol profiles across putatively herbivorous and nonherbivorous drosophilids. The results of these studies show that S. flava is an obligate herbivore of living plants. Paired with its genetic model host, Arabidopsis thaliana, S. flava is a novel and powerful system for exploring mechanisms underlying the evolution of herbivory, a complex trait that enabled the exceptional diversification of insects.
Higher trophic levels and species with poorer dispersal traits are more susceptible to habitat loss on island fragments
Authors: Wang Zhonghan , Chase Jonathan M. , Xu Wubing , Liu Jinliang , Wu Donghao , Zhang Aiying , Wang Jirui , Luo Yuanyuan , Yu Mingjian
Published: April 2024

Ongoing habitat loss and fragmentation caused by human activities represent one of the greatest causes of biodiversity loss. However, the effects of habitat loss and fragmentation are not felt equally among species. Here, we examined how habitat loss influenced the diversity and abundance of species from different trophic levels, with different traits, by taking advantage of an inadvertent experiment that created habitat islands from a once continuous forest via the creation of the Thousand Island Lake, a large reservoir in China. On 28 of these islands with more than a 9000‐fold difference in their area (0.12–1154 ha), we sampled plants, herbivorous insects, and predatory insects using effort‐controlled sampling and analyses. This allowed us to discern whether any observed differences in species diversity were due to passive sampling alone or to demographic effects that disproportionately influenced some species relative to others. We found that while most metrics of sampling effort‐controlled diversity increased with island area, the strength of the effect was exacerbated for species in higher trophic levels. When we more explicitly examined differences in species composition among islands, we found that the pairwise difference in species composition among islands was dominated by species turnover but that nestedness increased with differences in island area, indicating that some species are more likely to be absent from smaller islands. Furthermore, by examining trends of several dispersal‐related traits of species, we found that species with lower dispersal propensity tended to be those that were lost from smaller islands, which was observed for herbivorous and predatory insects. Our results emphasize the importance of incorporating within‐patch demographic effects, as well as the taxa and traits of species when understanding the influence of habitat loss on biodiversity.
Temporal associations of plasma levels of the secreted phospholipase A2 family and mortality in severe COVID‐19
Authors: Lu Eric , Hara Aki , Sun Shudong , Hallmark Brian , Snider Justin M. , Seeds Michael C. , Watkins Joseph C. , McCall Charles E. , Zhang Hao Helen , Yao Guang , Chilton Floyd H.
Published: April 2024

Previous research suggests that group IIA‐secreted phospholipase A2 (sPLA2‐IIA) plays a role in and predicts lethal COVID‐19 disease. The current study reanalyzed a longitudinal proteomic data set to determine the temporal relationship between levels of several members of a family of sPLA2 isoforms and the severity of COVID‐19 in 214 ICU patients. The levels of six secreted PLA2 isoforms, sPLA2‐IIA, sPLA2‐V, sPLA2‐X, sPLA2‐IB, sPLA2‐IIC, and sPLA2‐XVI, increased over the first 7 ICU days in those who succumbed to the disease but attenuated over the same time period in survivors. In contrast, a reversed pattern in sPLA2‐IID and sPLA2‐XIIB levels over 7 days suggests a protective role of these two isoforms. Furthermore, decision tree models demonstrated that sPLA2‐IIA outperformed top‐ranked cytokines and chemokines as a predictor of patient outcome. Taken together, proteomic analysis revealed temporal sPLA2 patterns that reflect the critical roles of sPLA2 isoforms in severe COVID‐19 disease.
The immunosuppressive drug cyclosporin A has an immunostimulatory function in CD8+ T cells
Authors: Wißfeld Jannis , Hering Marvin , ten Bosch Nora , Cui Guoliang
Published: April 2024

Cyclosporin A is a well‐established immunosuppressive drug used to treat or prevent graft‐versus‐host disease, the rejection of organ transplants, autoimmune disorders, and leukemia. It exerts its immunosuppressive effects by inhibiting calcineurin‐mediated dephosphorylation of the nuclear factor of activated T cells (NFAT), thus preventing its nuclear entry and suppressing T cell activation. Here we report an unexpected immunostimulatory effect of cyclosporin A in activating the mammalian target of rapamycin complex 1 (mTORC1), a crucial metabolic hub required for T cell activation. Through screening a panel of tool compounds known to regulate mTORC1 activation, we found that cyclosporin A activated mTORC1 in CD8+ T cells in a 3‐phosphoinositide‐dependent protein kinase 1 (PDK1) and protein kinase B (PKB/AKT)‐dependent manner. Mechanistically, cyclosporin A inhibited the calcineurin‐mediated AKT dephosphorylation, thereby stabilizing mTORC1 signaling. Cyclosporin A synergized with mTORC1 pathway inhibitors, leading to potent suppression of proliferation and cytokine production in CD8+ T cells and an increase in the killing of acute T cell leukemia cells. Consequently, relying solely on CsA is insufficient to achieve optimal therapeutic outcomes. It is necessary to simultaneously target both the calcineurin‐NFAT pathway and the mTORC1 pathway to maximize therapeutic efficacy.
Contribution of olive endogenous enzymes activities on virgin olive oil phenolic profile
Authors: Hbaieb Rim Hachicha , Kotti Faten , Gargouri Mohamed
Published: April 2024

Virgin olive oil (VOO) quality has been essentially correlated to its minor component contents, mainly phenolic compounds. Nevertheless, the content and composition of these compounds could be affected by several factors, among them the composition and biochemical properties of olive fruits, principally olive endogenous enzyme activities. Otherwise, the activities of these enzymes could be influenced by numerous factors, such as olive cultivars, ripening degree, olive storage conditions, and VOO extraction process. Thus, the objective of this review article is the focus on the key variation of olive endogenous enzyme activities according to these factors and their eventual contribution to the VOO phenolic profile.
Low‐ and moderate‐intensity aerobic exercise improves the physiological acclimatization of lowlanders on the Tibetan plateau
Authors: Su Rui , Han Chenxiao , Chen Guiquan , Li Hao , Liu Wanying , Wang Chengzhi , Zhang Wenrui , Zhang Yuming , Zhang Delong , Ma Hailin
Published: April 2024

This study investigates whether exercise as a strategy for improving physical fitness at sea level also offers comparable benefits in the unique context of high altitudes (HA), considering the physiological challenges of hypoxic conditions. Overall, 121 lowlanders who had lived on the Tibetan Plateau for >2 years and were still living at HA during the measurements were randomly classified into four groups. Each individual of the low‐intensity (LI), moderate‐intensity (MI), and high‐intensity (HI) groups performed 20 sessions of aerobic exercise at HA (3680 m) over 4 weeks, while the control group (CG) did not undergo any intervention. Physiological responses before and after the intervention were observed. The LI and MI groups experienced significant improvement in cardiopulmonary fitness (0.27 and 0.35 L/min increases in peak oxygen uptake [O2peak], both p < 0.05) after exercise intervention, while the hematocrit (HCT) remained unchanged (p > 0.05). However, HI exercise was less efficient for cardiopulmonary fitness of lowlanders (0.02 L/min decrease in O2peak, p > 0.05), whereas both the HCT (1.74 %, p < 0.001) and glomerular filtration rate (18.41 mL/min, p < 0.001) increased with HI intervention. Therefore, LI and MI aerobic exercise, rather than HI, can help lowlanders in Tibet become more acclimated to the HA by increasing cardiopulmonary function and counteracting erythrocytosis.
Within‐laboratory reproducibility of Ames test results: Are repeat tests necessary?
Authors: Zeiger Errol , Mitchell Constance A. , Pfuhler Stefan , Liao Yang , Witt Kristine L.
Published: April 2024

The Ames test is required by regulatory agencies worldwide for assessing the mutagenic and carcinogenic potential of chemical compounds. This test uses several strains of bacteria to evaluate mutation induction: positive results in the assay are predictive of rodent carcinogenicity. As an initial step to understanding how well the assay may detect mutagens present as constituents of complex mixtures such as botanical extracts, a cross‐sector working group examined the within‐laboratory reproducibility of the Ames test using the extensive, publicly available National Toxicology Program (NTP) Ames test database comprising more than 3000 distinct test articles, most of which are individual chemicals. This study focused primarily on NTP tests conducted using the standard Organization for Economic Co‐operation and Development Test Guideline 471 preincubation test protocol with 10% rat liver S9 for metabolic activation, although 30% rat S9 and 10 and 30% hamster liver S9 were also evaluated. The reproducibility of initial negative responses in all strains with and without 10% S9, was quite high, ranging from 95% to 99% with few exceptions. The within‐laboratory reproducibility of initial positive responses for strains TA98 and TA100 with and without 10% rat liver S9 was ≥90%. Similar results were seen with hamster S9. As expected, the reproducibility of initial equivocal responses was lower, <50%. These results will provide context for determining the optimal design of recommended test protocols for use in screening both individual chemicals and complex mixtures, including botanicals.