bluuebunny/crossref_metadata_2025 huggingface dataset:
Repair of noise-induced damage to stereocilia F-actin cores is facilitated by XIRP2 and its novel mechanosensor domain
Authors: Wagner Elizabeth L , Im Jun-Sub , Sala Stefano , Nakahata Maura I , Imbery Terence E , Li Sihan , Chen Daniel , Nimchuk Katherine , Noy Yael , Archer David W , Xu Wenhao , Hashisaki George , Avraham Karen B , Oakes Patrick W , Shin Jung-Bum
Published: June 2023

Prolonged exposure to loud noise has been shown to affect inner ear sensory hair cells in a variety of deleterious manners, including damaging the stereocilia core. The damaged sites can be visualized as ‘gaps’ in phalloidin staining of F-actin, and the enrichment of monomeric actin at these sites, along with an actin nucleator and crosslinker, suggests that localized remodeling occurs to repair the broken filaments. Herein, we show that gaps in mouse auditory hair cells are largely repaired within 1 week of traumatic noise exposure through the incorporation of newly synthesized actin. We provide evidence that Xin actin binding repeat containing 2 (XIRP2) is required for the repair process and facilitates the enrichment of monomeric γ-actin at gaps. Recruitment of XIRP2 to stereocilia gaps and stress fiber strain sites in fibroblasts is force-dependent, mediated by a novel mechanosensor domain located in the C-terminus of XIRP2. Our study describes a novel process by which hair cells can recover from sublethal hair bundle damage and which may contribute to recovery from temporary hearing threshold shifts and the prevention of age-related hearing loss.
A versatile high-throughput assay based on 3D ring-shaped cardiac tissues generated from human induced pluripotent stem cell-derived cardiomyocytes
Authors: Seguret Magali , Davidson Patricia , Robben Stijn , Jouve Charlène , Pereira Celine , Lelong Quitterie , Deshayes Lucille , Cerveau Cyril , Le Berre Maël , Rodrigues Ribeiro Rita S , Hulot Jean-Sébastien
Published: June 2023

We developed a 96-well plate assay which allows fast, reproducible, and high-throughput generation of 3D cardiac rings around a deformable optically transparent hydrogel (polyethylene glycol [PEG]) pillar of known stiffness. Human induced pluripotent stem cell-derived cardiomyocytes, mixed with normal human adult dermal fibroblasts in an optimized 3:1 ratio, self-organized to form ring-shaped cardiac constructs. Immunostaining showed that the fibroblasts form a basal layer in contact with the glass, stabilizing the muscular fiber above. Tissues started contracting around the pillar at D1 and their fractional shortening increased until D7, reaching a plateau at 25±1%, that was maintained up to 14 days. The average stress, calculated from the compaction of the central pillar during contractions, was 1.4±0.4 mN/mm2. The cardiac constructs recapitulated expected inotropic responses to calcium and various drugs (isoproterenol, verapamil) as well as the arrhythmogenic effects of dofetilide. This versatile high-throughput assay allows multiple in situ mechanical and structural readouts.
A miRNome analysis at the early postmortem interval
Authors: Guardado-Estrada Mariano , Cárdenas-Monroy Christian A. , Martínez-Rivera Vanessa , Cortez Fernanda , Pedraza-Lara Carlos , Millan-Catalan Oliver , Pérez-Plasencia Carlos
Published: June 2023

The postmortem interval (PMI) is the time elapsing since the death of an individual until the body is examined. Different molecules have been analyzed to better estimate the PMI with variable results. The miRNAs draw attention in the forensic field to estimate the PMI as they can better support degradation. In the present work, we analyzed the miRNome at early PMI in rats’ skeletal muscle using the Affymetrix GeneChip™ miRNA 4.0 microarrays. We found 156 dysregulated miRNAs in rats’ skeletal muscle at 24 h of PMI, out of which 84 were downregulated, and 72 upregulated. The miRNA most significantly downregulated was miR-139-5p (FC = −160, p = 9.97 × 10−11), while the most upregulated was rno-miR-92b-5p (FC = 241.18, p = 2.39 × 10−6). Regarding the targets of these dysregulated miRNAs, the rno-miR-125b-5p and rno-miR-138-5p were the miRNAs with more mRNA targets. The mRNA targets that we found in the present study participate in several biological processes such as interleukin secretion regulation, translation regulation, cell growth, or low oxygen response. In addition, we found a downregulation of SIRT1 mRNA and an upregulation of TGFBR2 mRNA at 24 h of PMI. These results suggest there is an active participation of miRNAs at early PMI which could be further explored to identify potential biomarkers for PMI estimation.
Raptor couples mTORC1 and ERK1/2 inhibition by cardamonin with oxidative stress induction in ovarian cancer cells
Authors: Zhu Yanting , Wang Shifeng , Niu Peiguang , Chen Huajiao , Zhou Jintuo , Jiang Li , Li Danyun , Shi Daohua
Published: June 2023

Background

A balance on nutrient supply and redox homeostasis is required for cell survival, and increased antioxidant capacity of cancer cells may lead to chemotherapy failure.

Objective

To investigate the mechanism of anti-proliferation of cardamonin by inducing oxidative stress in ovarian cancer cells.

Methods

After 24 h of drug treatment, CCK8 kit and wound healing test were used to detect cell viability and migration ability, respectively, and the ROS levels were detected by flow cytometry. The differential protein expression after cardamonin administration was analyzed by proteomics, and the protein level was detected by Western blotting.

Results

Cardamonin inhibited the cell growth, which was related to ROS accumulation. Proteomic analysis suggested that MAPK pathway might be involved in cardamonin-induced oxidative stress. Western blotting showed that cardamonin decreased Raptor expression and the activity of mTORC1 and ERK1/2. Same results were observed in Raptor KO cells. Notably, in Raptor KO cells, the effect of cardamonin was weakened.

Conclusion

Raptor mediated the function of cardamonin on cellular redox homeostasis and cell proliferation through mTORC1 and ERK1/2 pathways.
Bicol College Ed. D. and Ph. D. Graduates from 2012-2021: A Tracer Study
Authors: Esparrago Milagros
Published: June 2023

A school tracer study is a research method used to track the progress and outcomes of a school's graduates over time. In addition, school tracer studies can help to identify trends and patterns in education and employment outcomes across different countries and regions, allowing for cross-country comparisons and the identification of best practices. A tracer study on the Master of Science Graduates in Disaster Risk Management of the Central Bicol State University of Agriculture determined the employability of the Master of Science in Disaster Risk Management (MSDRM) graduates to provide input to curriculum innovation. The majority of the tracer studies reviewed were from the undergraduate and master’s levels. This tracer study on graduates of the doctoral programs, EdD and PhD of Bicol College Inc. is a novel undertaking. The descriptive–quantitative research design was used employing the saturated sampling technique.  A database of these graduates was established, and it was found that lifelong learning and service to the community are very relevant among doctoral degree graduates. Open career for postdoctoral studies is a challenge to them. Results showed that the majority of the respondents are females, with ages ranging from 40-60 years old. It took them 3-5 years to complete the degree, enroll in the degree program for professional growth and mostly be promoted after completion. Ten respondents obtained recognition and awards at the local, regional, national, and international level. One graduate even passed the Career Executive Service Written Examination, a qualification for directorship.
Attitudes and Language Proficiency of College Students at Catanduanes State University Panganiban Campus
Authors: Salvador Juvelyn
Published: June 2023

The study determined the attitudes toward the English language, the general proficiency level of 60 selected first-year college students, language structure, reading comprehension, and vocabulary. This was conducted to solve current issues of reading comprehension difficulties and poor linguistic competence in English subjects. It utilized descriptive research. Findings revealed “zero highly unfavorable” attitudes towards English; 2 “highly favorable.” For language structure, half of them were “slightly proficient,” 26 (43.33%) “Proficient,” 2 (3.33%) “Moderately proficient,” and 2 (3.33%) “Very poor.” No one obtained a “highly proficient” rating. The mean score: was 14.02, 4.59 standard deviation. The overall proficiency was “slightly proficient.” For vocabulary (context clues, antonym, analogy, denotation, and connotation), 29 (48.33%) rated “Slightly proficient,” 23 (38.33%) demonstrated “poor” performance, 6 (10%) were “moderately proficient” only 2 (3.33%) obtained “very poor” rating. The mean score is 13.52/ 4.15 standard deviation, a “slightly proficient” overall rating. “Connotation”- highest with a 3.50 mean score; lowest on “analogy “1.42 mean. For reading comprehension, 29 (48.33%) had “Slightly adequate” proficiency, 25 (41.67%) had “Poor” performance, 4 (6.67%) had a “Very poor” rating, 2(3.33%) had “Moderately proficient”- mean score 12.12, 3.51 standard deviation. “Poor” overall proficiency. “Forming opinions”- easiest; “drawing conclusion “- most difficult. The general proficiency level was “slightly proficient,” with a 42.23 mean. Respondent’s language structure and vocabulary are “slightly proficient, while “Poor” in reading comprehension.
Quality Evaluation of Mobile Application for Daily Mood Regulation: A Review and Analysis using the Mobile Application Rating Scale
Authors: An Soontae , Lee Hannah
Published: June 2023

Purpose: The purpose of this study is to provide an overview of mobile application (app) for mood management and to assess the quality of these application using the Mobile Application Rating Scale (MARS).Methods: The Google Play store was thoroughly explored in order to find apps that could help regulate daily moods. A total of 28 apps were selected. These mobile apps were analyzed with MARS questionnaires, which includes a total of 23 evaluation criteria organized into 6 categories (Engagement, Functionality, Aesthetics, Information, Subjective Quality, and App specific). In addition, we examined the features contained in of 28 different apps, focusing on those that measured mood and provided coping strategies.Results: The mean MARS score for the overall quality of the 28 apps was 3.48±0.81, with a maximum of 5 and a minimum of 0. Most apps received acceptable grades for Engagement and Aesthetics.Conclusion: MARS is a useful strategy for determining which apps can be recommended to users and which features should be modify to improve the quality of apps. This review shows that some apps match predetermined criteria for quality, content, or functionality, underlining the need for additional refining to evidence-based principles.
Risk Factors for Depressive Symptoms among Older Adults with Mild Cognitive Impairment: An Analysis of Data from the Eighth Korean Longitudinal Study of Aging 2020
Authors: Cho Mijung
Published: June 2023

Purpose: Cognitive impairment and depressive symptoms often accompany one another, as depressive symptoms often worsen cognitive impairment. This study aimed to identify the risk factors for depressive symptoms in older adults with mild cognitive impairment in Korea.Methods: This study analyzed data from the eighth Korean Longitudinal Study of Aging 2020. A total of 1,023 participants aged 65 and older were selected as participants whose scores on the Korean Mini-Mental State Examination ranged from 18 to 23. For data analysis, descriptive statistics, the Rao-Scott x2 test, and logistic regression using complex samples were performed.Results: The prevalence of depressive symptoms among participants was 33.2%. According to the logistic regression analysis, the significant risk factors affecting depressive symptoms in older adults with mild cognitive impairment were having a high education level (odds ratio [OR]=1.98, 95% confidence interval [CI]=1.23~3.16), low hand grip strength (OR=1.85, 95% CI=1.12~3.08), visual impairment (OR=3.31, 95% CI=1.36~8.04), good oral health status (OR=0.97, 95% CI=0.95~0.99), and rarely having contact with one’s neighbors (OR=2.52 95% CI=1.23~5.18). Among the different characteristics(demographic, health status, social, and economic), health status characteristics were identified as having the greatest influence on depressive symptoms in older adults with mild cognitive impairment.Conclusion: The results of this study suggest that a multidimensional nursing strategy including the regular management of health conditions is necessary to prevent depressive symptoms in older adults with mild cognitive impairment.
Time-related Complications in Patients with Traumatic Spinal Cord Injury according to the AIS Impairment Scale Grade: A Retrospective Review
Authors: Kim Jeounghee , Shin Yong Soon
Published: June 2023

Purpose: The aim of this study was to analyze time-dependent complications in patients with traumatic spinal cord injury (SCI) as a function of their initial neurological status determined by the ASIA Impairment Scale (AIS) grade.Methods: Consecutive patients with SCI who visited the emergency department at Asan Medical Center from 2005 to 2019 were included, and their electronic medical records were analyzed according to four time periods from initial visit to hospital discharge. Time-dependent SCI-related complications, including medical, urinary, musculoskeletal, and neurological complications and pain, were analyzed as well as the association between SCI complications and AIS grade. In-hospital recovery from neurological damage and long-term outcomes were also evaluated.Results: Of the 632 SCI patients who visited the emergency department during the study period, 110 patients were included in the study. The complication rates in patients initially assessed as AIS grades A, B, C, D, and E were 53.6%, 16.4%, 14.6%, 13.6%, and 1.8%, respectively. The most common complications after SCI were UTIs (n=37; 33.6%), pressure ulcers (n=36; 32.7%), neuropathic pain (n=34; 30.9%), and pneumonia (n=33; 30.0%). Patients with a poor neurological status (AIS grade A) had more medical complications and lower neurological resilience than did those with better neurological status (AIS grades B-E).Conclusion: Post-SCI complications differed by time after SCI and neurological status. Nurses should be aware that complications can occur at any time in patients with traumatic SCI. Patients with poorer AIS grades should be particularly closely observed and receive preventive care for complications.
DIÓTIMA, MAESTRA DE SÓCRATES EN EL CONOCIMIENTO DEL AMOR. SU PRESENCIA EN EL DIÁLOGO SIMPOSIO
Authors: Ugalde Quintana Jeannet
Published: June 2023

El presente artículo tiene dos objetivos. Por una parte, defender la realidad histórica de Diótima a partir del análisis de fuentes antiguas y de investigaciones de pensadores contemporáneos. Por otra parte, demostrar que el discurso sobre el amor que emite Sócrates en el diálogo Simposio forma parte de una enseñanza transmitida al filósofo ateniense por esta mujer, de tal manera que habría que considerar a Diótima, más que como una máscara de Sócrates, como la representación de una de las primeras filósofas en la historia del pensamiento occidental.
Análise da aplicação da contabilidade de gestão ambiental em uma indústria salineira
Authors: Lima Eli de Sousa , De Oliveira Auris Martins , Silva Sérgio Luiz Pedrosa , De Oliveira Adriana Martins , Valdevino Rosângela Queiroz Souza , Paiva Antonio Claudio Noberto , Almeida Cássio Rodrigo da Costa , Lopes Jorge Eduardo de Medeiros
Published: June 2023

A contabilidade de gestão ambiental tem adquirido grande relevo na esfera administrativa das organizações. No entanto, ainda é marcante e visível que muitas empresas têm negligenciado sua aplicação, investindo mais no aspecto meramente financeiro, colocando em segundo plano as questões do meio ambiente. Boa parte dessas organizações, sobretudo as do setor industrial são consideradas as maiores responsáveis pelos impactos ambientais. A contabilidade ambiental é uma ramificação da tradicional, mas não é uma imposição pelo governo, e sim uma ferramenta valorizada e utilizada por gestores que possuem uma visão estratégica sobre o cuidado com a natureza, focada na sustentabilidade. Quanto ao objetivo deste artigo, consiste em saber se a indústria analisada  tem  consciência da  importância da  contabilidade de  gestão  ambiental,                                   bem como se a mesma a utiliza no processo administrativo. Como metodologia, foi realizado um estudo de caso numa empresa do ramo salineiro localizada na cidade Grossos/RN. No que diz respeito ao modelo do plano de contas adotado pela empresa, bem como ao seu orçamento, foi constatado que não é efetuado uma separação entre as contas tradicionais (ativo, passivo, despesa, receita e custo) e as contas ambientais (ativo ambiental, passivo ambiental, despesa ambiental, receita ambiental e custo ambiental). Ao término da pesquisa, pôde-se verificar que a indústria salineira estudada, apesar de atribuir um enorme grau de importância à aplicação da contabilidade de gestão ambiental nas organizações, não a utiliza no processo de gestão dos seus negócios.
Correlation and Regression of Weed, ‎Growth and Yield Attributes of Transplanted Pearl Millet (Pennisetum ‎glaucum (L.) R. Br. Emend. Stunz)‎ as Affected by Weed Management Practices
Authors: Lekha S. J. Blessy , Kumar K. Udhaya , Silambarasan M. , Chetty M. Rinky
Published: June 2023

To evaluate the “Correlation and regression of weed, ‎growth and yield attributes of transplanted Pearl millet (Pennisetum ‎glaucum (L.) R. Br. Emend. Stunz)‎ as affected by weed management practices‎”. And the design of the trial was Randomized Complete Block Design (RBD).The field trial was conducted during the Rabi season 2022 at Experimental farm, Karunya Institute of Technology and Sciences, Coimbatore, Tamil Nadu. The experiment consisted of eight different treatments for weed management practices was replicated thrice. The soil type used was silty clay loam. The Pearl millet TNAU cumbu hybrid (CO9) was sown in the nursery and transplanted at 18 DAS and transplanted with a spacing of 45 x 15 cm. The following treatments were applied: T1 - PE of Atrazine 0.5 kg ha-1, T2 - PE of Oxyflurofen 0.250 kg ha-1, T3 - PE of Pendimethalin 0.75 kg ha-1, T4 - T1+ Hand Weeding on 30 DAT, T5 - T2+ Hand Weeding on 30 DAT, T6 - T3+ Hand Weeding on 30 DAT, T7 - Hand Weeding on 20 and 40 DAT and T8 - Unweeded check. Correlation analysis in weed management research assists researchers in assessing the strength and direction of relationships between variables. By understanding these relationships, researchers can gain insights into the factors influencing weed growth and develop focused management strategies. Moreover, correlation and regression studies provide valuable information for decision-making in weed management. The analysis showed positive correlation between grain yield and growth parameters viz., plant height at harvest (r = 0.965), LAI at 45 DAT (r = 0.852), DMP at 45 DAT (r = 0.971) and DMP at harvest (r = 0.973). Grain yield showed positive correlation with yield attributes, WCE and nutrient content viz., Productive tillers (r = 0.987), test weight (r =0.994), stover yield (r = 0.981), Weed Control Efficiency (r = 0.931), nitrogen uptake (r = 0.980), phosphorous uptake (r = 0.979) and potassium uptake (r = 0.962).This information can guide farmers, agronomists, and policymakers in making informed choices regarding management practices, resource allocation, and minimizing the economic and environmental impacts of weeds.
Study on the Effects Addition of Kinnow Juice on Sensory Properties of Kalakand
Authors: Maske G. V. , Londhe G. K. , Zine P. L.
Published: June 2023

Kalakand was prepared from buffalo milk (standardized with 6 per cent fat and 9 per cent SNF) with constant level of sugar (6 per cent by volume of milk) and different levels of kinnow juice (10, 15, 20 and 25 part by vol. of milk). It was observed that the overall acceptability score for treatment T1, T2, T3, T4 and T5 were 8.31, 8.37, 8.54, 8.19 and 7.83 respectively. As the level of kinnow juice in kalakand increases the overall acceptability score also increases upto treatment T3, thereafter it was decreased. The treatment (T3) comprises kinnow juice @ 15 per cent secured maximum score with 8.54 and lowest score was found to be 7.83 in treatment T5.
Safety of Targeted Axillary Dissection After Neoadjuvant Therapy in Patients With Node-Positive Breast Cancer
Authors: Kuemmel Sherko , Heil Joerg , Bruzas Simona , Breit Elisabeth , Schindowski Dorothea , Harrach Hakima , Chiari Ouafaa , Hellerhoff Karin , Bensmann Elena , Hanf Volker , Graßhoff Sven-Thomas , Deuschle Petra , Belke Kerstin , Polata Silke , Paepke Stefan , Warm Mathias , Meiler Johannes , Schindlbeck Christian , Ruhwedel Wencke , Beckmann Ulrike , Groh Ulrich , Dall Peter , Blohmer Jens-Uwe , Traut Alexander , Reinisch Mattea
Published: June 2023

Importance

The increasing use of neoadjuvant systemic therapy (NST) has led to substantial pathological complete response rates in patients with initially node-positive, early breast cancer, thereby questioning the need for axillary lymph node dissection (ALND). Targeted axillary dissection (TAD) is feasible for axillary staging; however, data on oncological safety are scarce.

Objective

To assess 3-year clinical outcomes in patients with node-positive breast cancer who underwent TAD alone or TAD with ALND.

Design, Setting, and Participants

The SenTa study is a prospective registry study and was conducted between January 2017 and October 2018. The registry includes 50 study centers in Germany. Patients with clinically node-positive breast cancer underwent clipping of the most suspicious lymph node (LN) before NST. After NST, the marked LNs and sentinel LNs were excised (TAD) followed by ALND according to the clinician’s choice. Patients who did not undergo TAD were excluded. Data analysis was performed in April 2022 after 43 months of follow-up.

Exposure

TAD alone vs TAD with ALND.

Main Outcomes and Measures

Three-year clinical outcomes were evaluated.

Results

Of 199 female patients, the median (IQR) age was 52 (45-60) years. A total of 182 patients (91.5%) had 1 to 3 suspicious LNs; 119 received TAD alone and 80 received TAD with ALND. Unadjusted invasive disease-free survival was 82.4% (95% CI, 71.5-89.4) in the TAD with ALND group and 91.2% (95% CI, 84.2-95.1) in the TAD alone group (P = .04); axillary recurrence rates were 1.4% (95% CI, 0-54.8) and 1.8% (95% CI, 0-36.4), respectively (P = .56). Adjusted multivariate Cox regression indicated that TAD alone was not associated with an increased risk of recurrence (hazard ratio [HR], 0.83; 95% CI, 0.34-2.05; P = .69) or death (HR, 1.07; 95% CI, 0.31-3.70; P = .91). Similar results were obtained for 152 patients with clinically node-negative breast cancer after NST (invasive disease-free survival: HR, 1.26; 95% CI, 0.27-5.87; P = .77; overall survival: HR, 0.81; 95% CI, 0.15-3.83; P = .74).

Conclusions and Relevance

These results suggest that TAD alone in patients with mostly good clinical response to NST and at least 3 TAD LNs may confer survival outcomes and recurrence rates similar to TAD with ALND.
Thermo‐Oxidative Aging Behavior and Lifetime Prediction of Rubber Latex Foam with Various Natural‐to‐Synthetic Ratios
Authors: Jin Mengsha , Huang Dongmei , Chen Chen , Feng Zhenmin , Jin Kan , Wang Wukang
Published: June 2023

Rubber latex foam (RLF) is widely used in daily life and its characteristics are active areas of research. However, the thermo‐oxidative aging behaviors of RLF at high temperatures have not been elucidated in detail. Herein this study, the aging degree and characteristics of five types of RLF materials with various ratios of natural rubber latex and synthetic rubber latex are investigated by using the yellowness index (YI), whiteness index, cross‐linking density, indentation density, and infrared spectrum. It is indicated in the results that the structural failure degree, YI, and cross‐linking density of the sample increased linearly with increasing natural‐to‐synthetic ratio (N/R ratio). It is observed that all RLF samples with various N/R ratios undergo aging reactions during the aging process, but the aging degree and aging rate of the samples differ. Furthermore, a lifetime prediction model is calculated by the standard method and the variable activation energy method, and the YI of RLF is used as an index to evaluate the service life, which serves as a useful tool for the quality evaluation of RLF.
Improved Tribocorrosion Properties of Ti6Al4V Alloy by Anodic Plasma Electrolytic Oxidation
Authors: Zeng Qunfeng , Wang Zhao , He Wanjun , Pang Zeming , Ning Zekun , Chen Ruiquan , Zheng Chenjie , Yan Chao , Guo Leilei
Published: June 2023

Ti6Al4V alloy has good corrosion resistance due to the formation of the passive oxide films on the surface of Ti6Al4V alloy. However, Ti6Al4V alloy has poor tribocorrosion resistance in the seawater environment. Herein the present work, plasma electrolytic oxidation (PEO) with the electrolyte of glycerol and sodium borate is used to generate PEO coatings on the surface of Ti6Al4V alloy to improve its tribocorrosion properties. The microstructure and tribocorrosion properties of PEO coatings are investigated by using scanning electron microscopy, X‐ray diffraction, and tribometer, respectively. The growth kinetics and the tribocorrosion mechanisms of PEO coatings are discussed in detail. It is shown in the results that PEO coatings deposited on the surface of Ti6Al4V alloy are composed of rutile and anatase phases. The surface hardness and thickness of PEO coatings are enhanced with the increase of the voltage and time. The wear rate of Ti6Al4V alloy with PEO coatings is significantly reduced in artificial seawater.
A Mitochondria‐Targeted NIR‐II AIEgen Induced Pyroptosis for Enhanced Tumor Immunotherapy
Authors: Yu Kaiwu , Ye Binglin , Yang Huang , Xu Xinxin , Mao Zhengwei , Zhang Qinghua , Tian Mei , Zhang Haoke , Zhang Hong , He Qinggang
Published: June 2023

Cancer immunotherapy is a favorable strategy for facilitating anti‐tumor immunity, but it shows limited benefits in clinical practice owing to the immunosuppressive tumor microenvironment. Pyroptosis shows great immunostimulatory effect on tumor, whereas the lack of pyroptotic inducer with imaging property has restricted its progress in tumor theranostics. Herein, a mitochondria‐targeted aggregation‐induced emission (AIE) luminogen (TPA‐2TIN) with NIR‐II emission is designed for highly efficient induction of tumor cell pyroptosis. The fabricated TPA‐2TIN nanoparticles can be efficiently taken up by tumor cells and selectively accumulated in tumor for a long term observed by NIR‐II fluorescence imaging. More importantly, the TPA‐2TIN nanoparticles can effectively stimulate immune responses both in vitro and in vivo mediated by the mitochondrial dysfunctions and the subsequent activation of the pyroptotic pathway. Ultimately, the reversal of the immunosuppressive tumor microenvironment significantly enhances the immune checkpoint therapy. This study paves a new avenue for adjuvant immunotherapy of cancer.
Machine learning of organic solvents reveals an extraordinary axis in Hansen space as indicator of spherical precipitation of polymers
Authors: Ihara Yuta , Yamagishi Hiroshi , Naito Masanobu , Yamamoto Yohei
Published: June 2023

Machine learning is an emerging tool in the field of materials chemistry for uncovering a principle from large datasets. Here, we focus on the spherical precipitation behavior of polymers and computationally extract a hidden trend that is orthogonal to the availability bias in the chemical space. For constructing a dataset, four polymers were precipitated from 416 solvent/nonsolvent combinations, and the morphology of the resulting precipitates were collected. The dataset was subjected to computational investigations consisting of principal component analysis and machine learning based on random forest model and support vector machine. Thereby, we eliminated the effect of the availability bias and found a linear combination of Hansen parameters to be the most suitable variable for predicting precipitation behavior. The predicted appropriate solvents are those with low hydrogen bonding capability, low polarity, and small molecular volume. Furthermore, we found that the capability for spherical precipitation is orthogonal to the availability bias and forms an extraordinary axis in Hansen space, which is the origin of the conventional difficulty in identifying the trend. The extraordinary axis points toward a void region, indicating the potential value of synthesizing novel solvents located therein.
Dinitrogen Functionalization with Carbon Dioxide and Carbon Disulfide Giving Symmetric and Unsymmetric Hydrazido Complexes
Authors: Ishida Yutaka , Hasegawa Sui , Kawaguchi Hiroyuki
Published: June 2023

Here we show that a tridentate bis(aryloxide)anilide‐ligated titanium/potassium scaffold promotes functionalization of coordinated N2 with CO2 and CS2 through formation of N−C bonds. Treatment of a naphthalene complex with N2 gave an end‐on bridging dinitrogen complex featuring a [Ti2K2N2] core. The dinitrogen complex underwent insertion of CO2 into each Ti−NN bond to afford an N,N′‐dicarboxylated hydrazido complex. Stepwise nitrogen‐carbon bond formation at coordinated N2 proceeded to afford an unsymmetric hydrazido complex upon sequentially treating the dinitrogen complex with CS2 and CO2. Addition of Me3SiCl to the dicarboxylated hydrazido complex resulted in partial silylation of the carboxylate groups but did not lead to removal of the functionalized N2 unit from the metal centers. However, reduction of the dicarboxylated hydrazido complex with potassium naphthalenide afforded an oxo‐bridged dinuclear complex along with release of free potassium cyanate.
Diversification of Glycosyl Compounds via Glycosyl Radicals
Authors: Jiang Yi , Zhang Yijun , Lee Boon Chong , Koh Ming Joo
Published: June 2023

Glycosyl radical functionalization is one of the central topics in synthetic carbohydrate chemistry. Recent advances in metal‐catalyzed cross‐coupling chemistry and metallaphotoredox catalysis provided powerful platforms for glycosyl radical diversification. In particular, the discovery of new glycosyl radical precursors in conjunction with these advanced reaction technologies have significantly expanded the space for glycosyl compound synthesis. In this Review, we highlight the most recent progress in this area starting from 2021, and the reports included will be categorized based on different reaction types for better clarity.
Framework‐Hotspot Enhanced Trans Cleavage of CRISPR‐Cas12a for Clinical Samples Detection
Authors: Li Fengqin , Li Junru , Yang Weiqiang , Yang Shuai , Chen Congshuo , Du Ling , Mei Junyang , Tang Qianyun , Chen Xiaojing , Yao Chi , Yang Dayong , Zuo Xiaolei , Liu Peifeng
Published: June 2023

The trans‐cleavage property of CRISPR‐Cas12a system makes it an excellent tool for disease diagnosis. Nevertheless, most methods based on CRISPR‐Cas system still require pre‐amplification of the target to achieve the desired detection sensitivity. Here we generate Framework‐Hotspot reporters (FHRs) with different local densities to investigate their effect on trans‐cleavage activity of Cas12a. We find that the cleavage efficiency increases and the cleavage rate accelerates with increasing reporter density. We further construct a modular sensing platform with CRISPR‐Cas12a‐based target recognition and FHR‐based signal transduction. Encouragingly, this modular platform enables sensitive (100 fM) and rapid (<15 min) detection of pathogen nucleic acids without pre‐amplification, as well as detection of tumor protein markers in clinical samples. The design provides a facile strategy for enhanced trans cleavage of Cas12a, which accelerates and broadens its applications in biosensing.
Bimetal‐Organic Framework Nanoboxes Enable Accelerated Redox Kinetics and Polysulfide Trapping for Lithium‐Sulfur Batteries
Authors: Zhu Zhuo , Zeng Yinxiang , Pei Zhihao , Luan Deyan , Wang Xin , Lou Xiong Wen (David)
Published: June 2023

Lithium‐sulfur (Li−S) batteries are considered as promising candidates for next‐generation energy storage systems in view of the high theoretical energy density and low cost of sulfur resources. The suppression of polysulfide diffusion and promotion of redox kinetics are the main challenges for Li−S batteries. Herein, we design and prepare a novel type of ZnCo‐based bimetallic metal–organic framework nanoboxes (ZnCo‐MOF NBs) to serve as a functional sulfur host for Li−S batteries. The hollow architecture of ZnCo‐MOF NBs can ensure fast charge transfer, improved sulfur utilization, and effective confinement of lithium polysulfides (LiPSs). The atomically dispersed Co−O4 sites in ZnCo‐MOF NBs can firmly capture LiPSs and electrocatalytically accelerate their conversion kinetics. Benefiting from the multiple structural advantages, the ZnCo‐MOF/S cathode shows high reversible capacity, impressive rate capability, and prolonged cycling performance for 300 cycles.
Solvation Structure with Enhanced Anionic Coordination for Stable Anodes in Lithium‐Oxygen Batteries
Authors: Huang Yaohui , Geng Jiarun , Jiang Zhuoliang , Ren Meng , Wen Bo , Chen Jun , Li Fujun
Published: June 2023

Li‐O2 batteries have garnered much attention due to their high theoretical energy density. However, the irreversible lithium plating/stripping on the anode limits their performance, which has been paid little attention. Herein, a solvation‐regulated strategy for stable lithium anodes in tetraethylene glycol dimethyl ether (G4) based electrolyte is attempted in Li‐O2 batteries. Trifluoroacetate anions (TFA−) with strong Li+ affinity are incorporated into the lithium bis(fluorosulfonyl)imide (LiTFSI)/G4 electrolyte to attenuate the Li+‐G4 interaction and form anion‐dominant solvates. The bisalt electrolyte with 0.5 M LiTFA and 0.5 M LiTFSI mitigates G4 decomposition and induces an inorganic‐rich solid electrolyte interphase (SEI). This contributes to decreased desolvation energy barrier from 58.20 to 46.31 kJ mol−1, compared with 1.0 M LiTFSI/G4, for facile interfacial Li+ diffusion and high efficiency. It yields extended lifespan of 120 cycles in Li‐O2 battery with a limited Li anode (7 mAh cm−2). This work gains comprehensive insights into rational electrolyte design for Li‐O2 batteries.
A Cysteine‐Directed Proximity‐Driven Crosslinking Method for Native Peptide Bicyclization
Authors: Chen Fa‐Jie , Pinnette Nicole , Yang Fan , Gao Jianmin
Published: June 2023

Efficient and site‐specific modification of native peptides and proteins is desirable for synthesizing antibody‐drug conjugates as well as for constructing chemically modified peptide libraries using genetically encoded platforms such as phage display. In particular, there is much interest in efficient multicyclization of native peptides due to the appeals of multicyclic peptides as therapeutics. However, conventional approaches for multicyclic peptide synthesis require orthogonal protecting groups or non‐proteinogenic clickable handles. Herein, we report a cysteine‐directed proximity‐driven strategy for the constructing bicyclic peptides from simple natural peptide precursors. This linear to bicycle transformation initiates with rapid cysteine labeling, which then triggers proximity‐driven amine‐selective cyclization. This bicyclization proceeds rapidly under physiologic conditions, yielding bicyclic peptides with a Cys‐Lys‐Cys, Lys‐Cys‐Lys or N‐terminus‐Cys‐Cys stapling pattern. We demonstrate the utility and power of this strategy by constructing bicyclic peptides fused to proteins as well as to the M13 phage, paving the way to phage display of novel bicyclic peptide libraries.
Dimeric Manganese‐Catalyzed Hydroalkenylation of Alkynes with a Versatile Silicon‐Based Directing Group
Authors: Pang Yubo , Chen Shuai , Han Jie , Zhu Chengjian , Zhao Chuan‐Gang , Xie Jin
Published: June 2023

Herein, we present a manganese‐catalyzed, branched‐selective hydroalkenylation of terminal alkynes, under mild conditions through facile installation of a versatile silanol as a removable directing group. With an alkenyl boronic acid as the coupling partner, this reaction produces stereodefined (E,E)‐1,3‐dienes with high regio‐, chemo‐ and stereoselectivity. The protocol features mild reaction conditions such as room temperature and an air atmosphere, while maintaining excellent functional group compatibility. The resulting 1,3‐dienesilanol products serve as versatile building blocks, as the removal of the silanol group allows for the synthesis of both branched terminal 1,3‐dienes for downstream coupling reactions, as well as stereoselective construction of linear (E,E)‐1,3‐dienes and (E,E,E)‐ or (E,E,Z)‐1,3,5‐trienes. In addition, a Diels–Alder cycloaddition can smoothly and selectively deliver silicon‐containing pentasubstituted cyclohexene derivatives. Mechanistic investigations, in conjunction with DFT calculations, suggest a bimetallic synergistic activation model to account for the observed enhanced catalytic efficiency and good regioselectivity.
A Highly Accurate pH Detection Method for Sweat Analysis using a Printed 96‐Microwell Colorimetric Sensor Array
Authors: Sasaki Yui , Lyu Xiaojun , Minami Tsuyoshi
Published: June 2023

Invited for this month's cover are is the collaborating group of Prof. Minami at The University of Tokyo. The cover picture shows a printed 96‐microwell paper‐based colorimetric sensor array to detect pH changes below the decimal point in human sweat. More information can be found in the Research Article by Yui Sasaki, Xiaojun Lyu, and Tsuyoshi Minami.
Multiple linear regression and artificial neural networks for highly selective cationic β‐diimine‐methallyl nickel (II) catalyst for styrene dimerization reaction to 1,3‐diphenyl‐1‐butene
Authors: Landolsi Kamel , Echouchene Fraj , Bajahzar Abdullah , Belmabrouk Hafedh , Msaddek Moncef
Published: June 2023

The objective of the present study is to develop predictive models to input and output parameters for linear styrene dimerization reactions. These reactions involve the conversion of two styrene molecules into 1,3‐diphenyl‐1‐butene, which is a commonly used intermediate in the production of various industrial chemicals. Multiple linear regression (MLR) and artificial neural network based on multilayer perceptron (MLP) and radial basis function were used to model 1,3‐diphenyl‐1‐butne dimerization process in order to evaluate its performance. The neural network has been trained and tested by experimental data. The effect of various parameters (such as complex concentration) on styrene conversion (Conv%) and turnover of frequency (TOF) has been investigated in the proposed work. The results found by the proposed predictive models were analyzed and compared with the experimental results. Based on the comparison of the results, the radial basis function neural network (RBFNN) model outperformed the other models (MLR and MLP) with a correlation coefficient of (0.987 for Conv% and 0.947 for TOF) and lower root mean square errors for the output parameters. This result demonstrates that the RBFNN is an efficient technique to predict the styrene conversion and turnover frequency of the dimerization reaction. It was exposed that the control strategies learned are robust and can be transferred to similar dimerization reaction configurations.
Synthesis and evaluation of multitarget new 2‐aminothiazole derivatives as potential anti‐Alzheimer's agents
Authors: Bardakkaya Merve , Kilic Burcu , Sagkan Rahsan Ilıkcı , Aksakal Fatma , Shakila Shakila , Dogruer Deniz S.
Published: June 2023

In this study, two diverse series of 2‐aminothiazole‐based multitarget compounds, one propenamide and the other propanamide derivatives, were designed and synthesized. Subsequently, their anticholinesterease and antioxidant (ORAC) activities were tested. Among them, compound 3e was the most potent acetylcholinesterase (AChE) inhibitor (AChE IC50 = 0.5 μM, butyrylcholinesterase [BChE] IC50 = 14.7 μM) and compound 9e was the most potent BChE inhibitor (AChE IC50 = 3.13 μM, BChE IC50 = 0.9 μM). Kinetic experiments showed that both compounds were mixed‐type inhibitors. According to the anticholinesterease activity results, five compounds (3e, 4e, 5e, 9d, and 9e) were selected for further activity studies, all of which are dual cholinesterase inhibitors. Then, selected compounds were investigated in terms of their metal chelation activity. Moreover, their neuroprotective effects against H2O2‐induced damage in the PC12 cell line were evaluated at 10 μM and the results showed that the neuroprotective effect of 3e was 53% compared with the reference ferulic acid (77%). 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) results of selected compounds revealed that the compounds were noncytotoxic. Additionally, 3e was more effective in reducing lipopolysaccharides‐induced interleukin‐1β (IL‐1β), IL‐6, tumor necrosis factor‐α (TNF‐α), and nitric oxide (NO) production in the human monocyte derived from patient with acute monocytic leukemia cell line compared with other selected compounds. Finally, a molecular docking study was also performed.
Greenness‐by‐design approach for developing novel UV spectrophotometric methodologies resolving a quaternary overlapping mixture
Authors: Abdelshakour Mohamed A. , Eissa Maya S. , Attala Khaled , Elsonbaty Ahmed , Abdel Salam Randa A. , Hadad Ghada M. , Mostafa Aziza E.
Published: June 2023

Greenness‐by‐design (GbD) is an approach that integrates green chemistry principles into the method development stage of analytical processes, aiming to reduce their environmental impact. In this work, we applied GbD to a novel univariate double divisor corrected amplitude (DDCA) method that can resolve a quaternary pharmaceutical mixture in a fixed‐dose polypill product. We also used a genetic algorithm as a chemometric modeling technique to select the informative variables for the analysis of the overlapping mixture. This resulted in more accurate and efficient predictive models. We used a computational approach to study the effect of solvents on the spectral resolution of the mixture and to minimize the spectral interferences caused by the solvent, thus achieving spectral resolution with minimal analytical effort and ecological footprint. The validated methods showed wide linear concentration ranges for the four components (1–30 µg/mL for losartan, 2.5–30 µg/mL for atorvastatin and aspirin, and 2.5–35 µg/mL for atenolol) and achieved high scores on the hexagon and spider charts, demonstrating their eco‐friendliness.
Crystal structure determination, molecular docking, and molecular dynamics of arylal dimedones as potential inhibitors for castrate‐resistant prostate cancer
Authors: R Chandan , Kiran K. S. , Chaithanya M. S. , M Aditya
Published: June 2023

Increased androgen receptor (AR) signaling brought on by higher intratumoral androgen production and AR amplification is associated with castrate‐resistant prostate cancer (CRPC). Cell proliferation in this case continues even during low expression of testosterone in the body. Aldo‐keto reductase family 1 member C3 (AKR1C3) is one of the most elevated genes in CRPC and catalyzes the formation of powerful AR ligands from inactive forms. The current work aimed to use the x‐ray method to investigate the ligand's crystal structure while also conducting molecular docking and molecular dynamics tests on the synthesized molecules against AKR1C3. As per the results obtained, the MM‐PBSA binding energies of inhibitors 2,2'‐((4‐methoxyphenyl)methylene)bis(3,4‐hydroxy‐5,5‐dimethylcyclohex‐2‐en‐1‐one is −132.456 kJ mol−1 and 2,2'‐(phenylmethylene)bis(3‐hydroxy‐5,5‐dimethylcyclohex‐2‐en‐1‐one is −81.017 kJ mol−1. These results create a promising approach to drug design based on its fit to the structures of the receptor site rather than basing it on analogies to other active structures.
Pulsed Electromagnetic Fields Improved Peripheral Nerve Regeneration After Delayed Repair of One Month
Authors: Keyan Zhu , Liqian Zhang , Xinzhong Xu , Juehua Jing , Chungui Xu
Published: June 2023

The goal of this study was to determine if postoperative pulsed electromagnetic fields (PEMFs) could improve the neuromuscular rehabilitation after delayed repair of peripheral nerve injuries. Thirty‐six Sprague–Dawley rats were randomly divided into sham group, control group, and PEMFs group. The sciatic nerves were transected except for the control group. One month later, the nerve ends of the former two groups were reconnected. PEMFs group of rats was subjected to PEMFs thereafter. Control group and sham group received no treatment. Four and 8 weeks later, morphological and functional changes were measured. Four and eight weeks postoperatively, compared to sham group, the sciatic functional indices (SFIs) of PEMFs group were higher. More axons regenerated distally in PEMFs group. The fiber diameters of PEMFs group were larger. However, the axon diameters and myelin thicknesses were not different between these two groups. The brain‐derived neurotrophic factor and vascular endothelial growth factor expressions were higher in PEMFs group after 8 weeks. Semi‐quantitative IOD analysis for the intensity of positive staining indicated that there were more BDNF, VEGF, and NF200 in PEMFs group. It's concluded that PEMFs have effect on the axonal regeneration after delayed nerve repair of one month. The upregulated expressions of BDNF and VEGF may play roles in this process. © 2023 Bioelectromagnetics Society.
Evaluating cancer screening programs using survival analysis
Authors: Vratanar Bor , Pohar Perme Maja
Published: June 2023

The main purpose of cancer screening programs is to provide early treatment to patients that are diagnosed with cancer on a screening test, thus increasing their chances of survival. To test this hypothesis directly, one should compare the survival of screen‐detected cases to the survival of their counterparts not included to the program. In this study, we develop a general notation and use it to formally define the comparison of interest. We explain why the naive comparison between screen‐detected and interval cases is biased and show that the total bias that arises in this case can be decomposed as a sum of lead time bias, length time bias, and bias due to overdetection. With respect to the estimation, we show what can be estimated using existing methods. To fill in the missing gap, we develop a new nonparametric estimator that allows us to estimate the survival of the control group, that is, the survival of cancer cases that would be screen‐detected among those not included to the program. By joining the proposed estimator with existing methods, we show that the contrast of interest can be estimated without neglecting any of the biases. Our approach is illustrated using simulations and empirical data.