bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital twins elucidate critical role of Tscm in clinical persistence of TCR-engineered cell therapy
Authors: Joslyn Louis R. , Huang Weize , Miles Dale , Hosseini Iraj , Ramanujan Saroja
Published: January 2024

Despite recent progress in adoptive T cell therapy for cancer, understanding and predicting the kinetics of infused T cells remains a challenge. Multiple factors can impact the distribution, expansion, and decay or persistence of infused T cells in patients. We have developed a novel quantitative systems pharmacology (QSP) model of TCR-transgenic T cell therapy in patients with solid tumors to describe the kinetics of endogenous T cells and multiple memory subsets of engineered T cells after infusion. These T cells undergo lymphodepletion, proliferation, trafficking, differentiation, and apoptosis in blood, lymph nodes, tumor site, and other peripheral tissues. Using the model, we generated patient-matched digital twins that recapitulate the circulating T cell kinetics reported from a clinical trial of TCR-engineered T cells targeting E7 in patients with metastatic HPV-associated epithelial cancers. Analyses of key parameters influencing cell kinetics and differences among digital twins identify stem cell-like memory T cells (Tscm) cells as an important determinant of both expansion and persistence and suggest that Tscm-related differences contribute significantly to the observed variability in cellular kinetics among patients. We simulated in silico clinical trials using digital twins and predict that Tscm enrichment in the infused product improves persistence of the engineered T cells and could enable administration of a lower dose. Finally, we verified the broader relevance of the QSP model, the digital twins, and findings on the importance of Tscm enrichment by predicting kinetics for two patients with pancreatic cancer treated with KRAS G12D targeting T cell therapy. This work offers insight into the key role of Tscm biology on T cell kinetics and provides a quantitative framework to evaluate cellular kinetics for future efforts in the development and clinical application of TCR-engineered T cell therapies.
Large-scale computational modelling of the M1 and M2 synovial macrophages in rheumatoid arthritis
Authors: Zerrouk Naouel , Alcraft Rachel , Hall Benjamin A. , Augé Franck , Niarakis Anna
Published: January 2024

Macrophages play an essential role in rheumatoid arthritis. Depending on their phenotype (M1 or M2), they can play a role in the initiation or resolution of inflammation. The M1/M2 ratio in rheumatoid arthritis is higher than in healthy controls. Despite this, no treatment targeting specifically macrophages is currently used in clinics. Thus, devising strategies to selectively deplete proinflammatory macrophages and promote anti-inflammatory macrophages could be a promising therapeutic approach. State-of-the-art molecular interaction maps of M1 and M2 macrophages in rheumatoid arthritis are available and represent a dense source of knowledge; however, these maps remain limited by their static nature. Discrete dynamic modelling can be employed to study the emergent behaviours of these systems. Nevertheless, handling such large-scale models is challenging. Due to their massive size, it is computationally demanding to identify biologically relevant states in a cell- and disease-specific context. In this work, we developed an efficient computational framework that converts molecular interaction maps into Boolean models using the CaSQ tool. Next, we used a newly developed version of the BMA tool deployed to a high-performance computing cluster to identify the models’ steady states. The identified attractors are then validated using gene expression data sets and prior knowledge. We successfully applied our framework to generate and calibrate the M1 and M2 macrophage Boolean models for rheumatoid arthritis. Using KO simulations, we identified NFkB, JAK1/JAK2, and ERK1/Notch1 as potential targets that could selectively suppress proinflammatory macrophages and GSK3B as a promising target that could promote anti-inflammatory macrophages in rheumatoid arthritis.
Adjusting for genetic confounders in transcriptome-wide association studies improves discovery of risk genes of complex traits
Authors: Zhao Siming , Crouse Wesley , Qian Sheng , Luo Kaixuan , Stephens Matthew , He Xin
Published: January 2024

Many methods have been developed to leverage expression quantitative trait loci (eQTL) data to nominate candidate genes from genome-wide association studies. These methods, including colocalization, transcriptome-wide association studies (TWAS) and Mendelian randomization-based methods; however, all suffer from a key problem—when assessing the role of a gene in a trait using its eQTLs, nearby variants and genetic components of other genes’ expression may be correlated with these eQTLs and have direct effects on the trait, acting as potential confounders. Our extensive simulations showed that existing methods fail to account for these ‘genetic confounders’, resulting in severe inflation of false positives. Our new method, causal-TWAS (cTWAS), borrows ideas from statistical fine-mapping and allows us to adjust all genetic confounders. cTWAS showed calibrated false discovery rates in simulations, and its application on several common traits discovered new candidate genes. In conclusion, cTWAS provides a robust statistical framework for gene discovery.
Chromosome-level genome assemblies of Nicotiana tabacum, Nicotiana sylvestris, and Nicotiana tomentosiformis
Authors: Sierro Nicolas , Auberson Mehdi , Dulize Rémi , Ivanov Nikolai V.
Published: January 2024

The Solanaceae species Nicotiana tabacum, an economically important crop plant cultivated worldwide, is an allotetraploid species that appeared about 200,000 years ago as the result of the hybridization of diploid ancestors of Nicotiana sylvestris and Nicotiana tomentosiformis. The previously published genome assemblies for these three species relied primarily on short-reads, and the obtained pseudochromosomes only partially covered the genomes. In this study, we generated annotated de novo chromosome-level genomes of N. tabacum, N. sylvestris, and N. tomentosiformis, which contain 3.99 Gb, 2.32 Gb, and 1.74 Gb, respectively of sequence data, with 97.6%, 99.5%, and 95.9% aligned in chromosomes, and represent 99.2%, 98.3%, and 98.5% of the near-universal single-copy orthologs Solanaceae genes. The completion levels of these chromosome-level genomes for N. tabacum, N. sylvestris, and N. tomentosiformis are comparable to other reference Solanaceae genomes, enabling more efficient synteny-based cross-species research.
Extended-wavelength diffuse reflectance spectroscopy dataset of animal tissues for bone-related biomedical applications
Authors: Li Celina L. , Fisher Carl J. , Komolibus Katarzyna , Lu Huihui , Burke Ray , Visentin Andrea , Andersson-Engels Stefan
Published: January 2024

Diffuse reflectance spectroscopy (DRS) has been extensively studied in both preclinical and clinical settings for multiple applications, notably as a minimally invasive diagnostic tool for tissue identification and disease delineation. In this study, extended-wavelength DRS (EWDRS) measurements of ex vivo tissues ranging from ultraviolet through visible to the short-wave infrared region (355–1919 nm) are presented in two datasets. The first dataset contains labelled EWDRS measurements collected from bone cement samples and ovine specimens including 10 tissue types commonly encountered in orthopedic surgeries for data curation purposes. The other dataset includes labelled EWDRS measurements of primarily bone structures at different depths during stepwise drilling into intact porcine skulls until plunging into the cranial cavity. The raw data with code for pre-processing and calibration is publicly available for reuse on figshare. The datasets can be utilized not only for exploratory purposes in machine learning model construction, but also for knowledge discovery in the orthopedic domain to identify important features for surgical guidance, extract physiological parameters and provide diagnostic insights.
Improving the precision of shock resuscitation by predicting fluid responsiveness with machine learning and arterial blood pressure waveform data
Authors: Gupta Chitrabhanu B. , Basu Debraj , Williams Timothy K. , Neff Lucas P. , Johnson Michael A. , Patel Nathan T. , Ganapathy Aravindh S. , Lane Magan R. , Radaei Fatemeh , Chuah Chen-Nee , Adams Jason Y.
Published: January 2024

Fluid bolus therapy (FBT) is fundamental to the management of circulatory shock in critical care but balancing the benefits and toxicities of FBT has proven challenging in individual patients. Improved predictors of the hemodynamic response to a fluid bolus, commonly referred to as a fluid challenge, are needed to limit non-beneficial fluid administration and to enable automated clinical decision support and patient-specific precision critical care management. In this study we retrospectively analyzed data from 394 fluid boluses from 58 pigs subjected to either hemorrhagic or distributive shock. All animals had continuous blood pressure and cardiac output monitored throughout the study. Using this data, we developed a machine learning (ML) model to predict the hemodynamic response to a fluid challenge using only arterial blood pressure waveform data as the input. A Random Forest binary classifier referred to as the ML fluid responsiveness algorithm (MLFRA) was trained to detect fluid responsiveness (FR), defined as a ≥ 15% change in cardiac stroke volume after a fluid challenge. We then compared its performance to pulse pressure variation, a commonly used metric of FR. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC), confusion matrix metrics, and calibration curves plotting predicted probabilities against observed outcomes. Across multiple train/test splits and feature selection methods designed to assess performance in the setting of small sample size conditions typical of large animal experiments, the MLFRA achieved an average AUROC, recall (sensitivity), specificity, and precision of 0.82, 0.86, 0.62. and 0.76, respectively. In the same datasets, pulse pressure variation had an AUROC, recall, specificity, and precision of 0.73, 0.91, 0.49, and 0.71, respectively. The MLFRA was generally well-calibrated across its range of predicted probabilities and appeared to perform equally well across physiologic conditions. These results suggest that ML, using only inputs from arterial blood pressure monitoring, may substantially improve the accuracy of predicting FR compared to the use of pulse pressure variation. If generalizable, these methods may enable more effective, automated precision management of critically ill patients with circulatory shock.
Undrained shear behavior of silty sand with a constant state parameter considering initial stress anisotropy effect
Authors: Li Peipei , Zhu Chen , Pan Xiaodong , Lv Bin , Pan Kun
Published: January 2024

Field observations in sedimentation and erosion-prone areas indicate that most natural sand deposits may contain a certain amount of non-plastic fines and are often under anisotropic stress conditions. A series of triaxial compression tests were performed on clean and silty sand with fines content fc ranging from 0 to 20% at an initial mean effective stress of p0′ = 100 kPa and varying consolidation conditions to understand the impact of initial stress anisotropy on undrained shear behavior. The results indicate that the state parameter ψ is a superior predictor for characterizing the responses of sand-fines mixtures compared to the global void ratio and relative density. A comparison of the behavior of clean and silty sand with a constant ψ (= − 0.03) confirms that the sample with 10% fc exhibits the strongest dilation and greatest shear resistance, irrespective of the consolidation conditions. It is also demonstrated that the initial stress anisotropy with a comparably higher static stress ratio ηs typically diminishes the shear strength of mixtures. However, the influence of initial stress anisotropy on soil stiffness is not unilateral. The sample consolidated to a negative ηs is stiffer than that under isotropic consolidation, while the presence of a positive ηs leads to a decrease in the secant Young's modulus.
Genome-wide identification of the B3 transcription factor family in pepper (Capsicum annuum) and expression patterns during fruit ripening
Authors: Wang Tao , Long Cha , Chang Meixia , Wu Yuan , Su Shixian , Wei Jingjiang , Jiang Suyan , Wang Xiujun , He Jianwen , Xing Dan , He Yangbo , Ran Yaoqi , Li Wei
Published: January 2024

In plants, B3 transcription factors play important roles in a variety of aspects of their growth and development. While the B3 transcription factor has been extensively identified and studied in numerous species, there is limited knowledge regarding its B3 superfamily in pepper. Through the utilization of genome-wide sequence analysis, we identified a total of 106 B3 genes from pepper (Capsicum annuum), they are categorized into four subfamilies: RAV, ARF, LAV, and REM. Chromosome distribution, genetic structure, motif, and cis-acting element of the pepper B3 protein were analyzed. Conserved gene structure and motifs outside the B3 domain provided strong evidence for phylogenetic relationships, allowing potential functions to be deduced by comparison with homologous genes from Arabidopsis. According to the high-throughput transcriptome sequencing analysis, expression patterns differ during different phases of fruit development in the majority of the 106 B3 pepper genes. By using qRT-PCR analysis, similar expression patterns in fruits from various time periods were discovered. In addition, further analysis of the CaRAV4 gene showed that its expression level decreased with fruit ripening and located in the nucleus. B3 transcription factors have been genome-wide characterized in a variety of crops, but the present study is the first genome-wide analysis of the B3 superfamily in pepper. More importantly, although B3 transcription factors play key regulatory roles in fruit development, it is uncertain whether B3 transcription factors are involved in the regulation of the fruit development and ripening process in pepper and their specific regulatory mechanisms because the molecular mechanisms of the process have not been fully explained. The results of the study provide a foundation and new insights into the potential regulatory functions and molecular mechanisms of B3 genes in the development and ripening process of pepper fruits, and provide a solid theoretical foundation for the enhancement of the quality of peppers and their selection and breeding of high-yield varieties.
A genetic toolkit underlying the queen phenotype in termites with totipotent workers
Authors: Lin Silu , Elsner Daniel , Ams Leon , Korb Judith , Rosengaus Rebeca
Published: January 2024

Social insect castes (e.g., queens, workers) are prime examples of phenotypic plasticity (i.e., different phenotypes arising from the same genotype). Yet, the mechanisms that give rise to highly fertile, long-lived queens versus non-reproducing, short-lived workers are not well understood. Recently, a module of co-expressed genes has been identified that characterizes queens compared to workers of the termite Cryptotermes secundus (Kalotermitidae): the Queen Central Module (QCM). We tested whether the QCM is shared in termite species, in which queens gradually develop via early larval and late larval instars, the latter functioning as totipotent workers (linear development). Similar as in C. secundus, gene expression profiles revealed an enrichment of QCM genes in Zootermopsis angusticollis queens, a species from another termite family (Archotermopsidae). The expression of these QCM genes became gradually enriched during development from early larval instars via workers to queens. Thus, our results support the hypothesis of a conserved genetic toolkit that characterizes termite queens with gradual linear development. Our data also imply a strong caste-specific tissue specificity with the QCM signal being restricted to head-prothorax tissues in termite queens. This tissue-specific expression of key aging-related genes might have facilitated the evolution of a long lifespan in termite queens.
Towards effectiveness of cell free DNA based liquid biopsy in head and neck squamous cell carcinoma
Authors: Kowal-Wisniewska Ewelina , Jaskiewicz Katarzyna , Bartochowska Anna , Kiwerska Katarzyna , Ustaszewski Adam , Gorecki Tomasz , Giefing Maciej , Paluszczak Jaroslaw , Wierzbicka Malgorzata , Jarmuz-Szymczak Malgorzata
Published: January 2024

Liquid biopsy is a minimally invasive procedure, that uses body fluids sampling to detect and characterize cancer fingerprints. It is of great potential in oncology, however there are challenges associated with the proper handling of liquid biopsy samples that need to be addressed to implement such analysis in patients’ care. Therefore, in this study we performed optimization of pre-analytical conditions and detailed characterization of cfDNA fraction (concentration, length, integrity score) in surgically treated HNSCC patients (n = 152) and healthy volunteers (n = 56). We observed significantly higher cfDNA concentration in patients compared to healthy controls (p < 0.0001) and a time dependent decrease of cfDNA concentration after tumor resection. Our results also revealed a significant increase of cfDNA concentration with age in both, healthy volunteers (p = 0.04) and HNSCC patients (p = 0.000002). Moreover, considering the multitude of HNSCC locations, we showed the lack of difference in cfDNA concentration depending on the anatomical location. Furthermore, we demonstrated a trend toward higher cfDNA length (range 35–10380 and 500–10380 bp) in the group of patients with recurrence during follow-up. In conclusion, our study provide a broad characterization of cfDNA fractions in HNSCC patients and healthy controls. These findings point to several aspects necessary to consider when implementing liquid biopsy in clinical practice including: (I) time required for epithelial regeneration to avoid falsely elevated levels of cfDNA not resulting from active cancer, (II) age-related accumulation of nucleic acids accompanied by less efficient elimination of cfDNA and (III) higher cfDNA length in patients with recurrence during follow-up, reflecting predominance of tumor necrosis.
Association of TyG index and central obesity with hypertension in middle-aged and elderly Chinese adults: a prospective cohort study
Authors: Chen Yang , Hu Peng , He Yangyang , Qin Hao , Hu Longlong , Yang Renqiang
Published: January 2024

Triglyceride glucose index (TyG) and waist circumstance have been well documented to be highly correlated with hypertension. However, the joint effect of waist circumstance and TyG on the risk of hypertension is unknown in middle-aged and elderly Chinese adults. The purpose of this study was to investigate the association between TyG and the risk of new-onset hypertension in middle-aged and elderly Chinese individuals with different waist circumstances. The multicentred prospective cohort study was conducted in 28 provinces of China including a total of 5865 eligible participants aged ≥ 45 years old. Cox regression was performed to examine the relationship of TyG index and hypertension with adjustments for the pertinent variables. Besides, the relationship was explored in different groups on the basis of waist circumstance. There was no significant correlation between TyG index and new-onset hypertension after adjustment for pertinent variables (hazards ratio [HR]: 0.99; 95% confidence interval [CI]: 0.80–1.24). When the association was explored in different waist circumstance groups, multivariate cox regression analyses revealed that TyG was an independent factor positively associated with the risk of hypertension in central obesity prophase group (HR: 1.57; 95% CI 1.13–2.16). Among individuals with central obesity, relative to population with lower TyG (Q1: 4.96–8.18), people who had higher TyG (Q3: 8.52–8.95; Q4: 8.95–12.14) were associated with significantly lower HR for hypertension. There was no conspicuous correlation between TyG index with new-onset hypertension in normal waist circumstance (HR: 1.05; 95% CI 0.84–1.30). The research demonstrated the positive relationship of TyG with risk of hypertension among individuals with central obesity prophase, negative relationship of TyG with hypertension among population with central obesity and inconspicuous correlation of TyG with hypertension among individuals with normal waist. In conclusion, the study findings supported the combined effects of TyG index and waist circumference in predicting hypertension in middle-aged and elderly Chinese individuals.
Illumina reads correction: evaluation and improvements
Authors: Długosz Maciej , Deorowicz Sebastian
Published: January 2024

The paper focuses on the correction of Illumina WGS sequencing reads. We provide an extensive evaluation of the existing correctors. To this end, we measure an impact of the correction on variant calling (VC) as well as de novo assembly. It shows, that in selected cases read correction improves the VC results quality. We also examine the algorithms behaviour in a processing of Illumina NovaSeq reads, with different reads quality characteristics than in older sequencers. We show that most of the algorithms are ready to cope with such reads. Finally, we introduce a new version of RECKONER, our read corrector, by optimizing it and equipping with a new correction strategy. Currently, RECKONER allows to correct high-coverage human reads in less than 2.5 h, is able to cope with two types of reads errors: indels and substitutions, and utilizes a new, based on a two lengths of oligomers, correction verification technique.
Assessing the effects of foot strike patterns and shoe types on the control of leg length and orientation in running
Authors: Garofolini Alessandro , Mickle Karen J. , McLaughlin Patrick , Taylor Simon B.
Published: January 2024

This research investigates the stabilization of leg length and orientation during the landing phase of running, examining the effects of different footwear and foot strike patterns. Analyzing kinematic data from twenty male long-distance runners, both rearfoot and forefoot strikers, we utilized the Uncontrolled Manifold approach to assess stability. Findings reveal that both leg length and orientation are indeed stabilized during landing, challenging the hypothesis that rearfoot strikers exhibit less variance in deviations than forefoot strikers, and that increased footwear assistance would reduce these deviations. Surprisingly, footwear with a lower minimalist index enhanced post-landing stability, suggesting that cushioning contributes to both force dissipation and leg length stability. The study indicates that both foot strike patterns are capable of effectively reducing task-relevant variance, with no inherent restriction on flexibility for rearfoot strikers. However, there is an indication of potential reliance on footwear for stability. These insights advance our understanding of the biomechanics of running, highlighting the role of footwear in stabilizing leg length and orientation, which has significant implications for running efficiency and injury prevention.
Simulated microgravity improves maturation of cardiomyocytes derived from human induced pluripotent stem cells
Authors: Forghani Parvin , Rashid Aysha , Armand Lawrence C. , Wolfson David , Liu Rui , Cho Hee Cheol , Maxwell Joshua T. , Jo Hanjoong , Salaita Khalid , Xu Chunhui
Published: January 2024

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) possess tremendous potential for basic research and translational application. However, these cells structurally and functionally resemble fetal cardiomyocytes, which is a major limitation of these cells. Microgravity can significantly alter cell behavior and function. Here we investigated the effect of simulated microgravity on hiPSC-CM maturation. Following culture under simulated microgravity in a random positioning machine for 7 days, 3D hiPSC-CMs had increased mitochondrial content as detected by a mitochondrial protein and mitochondrial DNA to nuclear DNA ratio. The cells also had increased mitochondrial membrane potential. Consistently, simulated microgravity increased mitochondrial respiration in 3D hiPSC-CMs, as indicated by higher levels of maximal respiration and ATP content, suggesting improved metabolic maturation in simulated microgravity cultures compared with cultures under normal gravity. Cells from simulated microgravity cultures also had improved Ca2+ transient parameters, a functional characteristic of more mature cardiomyocytes. In addition, these cells had improved structural properties associated with more mature cardiomyocytes, including increased sarcomere length, z-disc length, nuclear diameter, and nuclear eccentricity. These findings indicate that microgravity enhances the maturation of hiPSC-CMs at the structural, metabolic, and functional levels.
Trends and factors associated with teenage pregnancy in Ethiopia: multivariate decomposition analysis
Authors: Zemene Melkamu Aderajew , Dagnaw Fentaw Teshome , Anley Denekew Tenaw , Dagnew Enyew , Zewdie Amare , Haimanot Aysheshim Belaineh , Dessie Anteneh Mengist
Published: January 2024

Teenage is a time of transition from childhood to adulthood. This stage is a time of change and needs particular care and ongoing support. Adolescent pregnancy remains a common health care problem in low- and middle-income countries, and it is associated with higher maternal and neonatal complications. Thus, this study aimed to determine the trends and factors associated with them that either positively or negatively contributed to the change in teenage pregnancy in Ethiopia. Ethiopian Demographic and Health Survey data from 2005 to 2016 were used for this study. A total weighted sample of 10,655 (3265 in 2005, 4009 in 2011, and 3381 in 2016) teenagers was included. Trends and the proportion of teenage pregnancies for each factor over time were explored. Then, a logit-based multivariate decomposition analysis for a non-linear response model was fitted to identify the factors that contributed to the change in teenage pregnancy. Statistical significance was declared at p-value < 0.05 and the analysis was carried out on weighted data. Teenage pregnancy declined significantly from 16.6% (95% CI: 15.4, 17.9) to 12.5% (95% CI: 11.4, 13.6) in the study period, with an annual reduction rate of 2.5%. About 49.8% of the decrease in teenage pregnancy was attributed to the change in the effect of the characteristics. The compositional change in primary educational status (41.8%), secondary or above educational status (24.55%), being from households with a rich wealth index (1.41%) were factors positively contributed to the decline in teenage pregnancy, whereas being from a Muslim religion (−12.5%) was the factor that negatively contributed to the reduction in teenage pregnancy. This study has shown that teenage pregnancy declined significantly; however, it is still unacceptably high. The changes in compositional factors of teenagers were responsible for the observed reduction in the prevalence of teen pregnancy rates in Ethiopia. Educational status, religion, and wealth index were found to be significant factors that contributed to the reduction in teenage pregnancy. Therefore, intervention programs targeting adolescents should address the socio-economic inequalities of these influential factors to reduce teenage pregnancy and related complications.
Design of a novel analogue peptide with potent antibiofilm activities against Staphylococcus aureus based upon a sapecin B-derived peptide
Authors: Akhash Nasim , Farajzadeh Sheikh Ahmad , Farshadzadeh Zahra
Published: January 2024

Nowadays, antimicrobial peptides are promising to confront the existing global crisis of antibiotic resistance. Here, a novel analogue peptide (mKLK) was designed based upon a D-form amidated sapecin B-derived peptide (KLK) by replacing two lysine residues with two tryptophan and one leucine by lysine, and inserting one alanine. The mKLK displayed superior amphipathic helixes in which the most of hydrophobic residues are confined to one face of the helix and had a higher hydrophobic moment compared with KLK. The mKLK retained its antibacterial activity and structure in human serum, suggesting its stability to proteolytic degradation. The values of MIC and MBC for mKLK were equal to those of KLK against clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA). However, mKLK showed more capability of in vitro inhibiting, eradicating, and dispersing MRSA and MSSA biofilms compared with KLK. Furthermore, a remarkable inhibitory activity of mKLK against MRSA and MSSA biofilms was seen in the murine model of catheter-associated biofilm infection. Results of this study show that mKLK not only exhibits antibacterial activity and serum stability but also a potent biofilm inhibitory activity at sub-MIC concentrations, confirming its potential therapeutic advantage for preventing biofilm-associated MRSA and MSSA infections.
The significant influence of the Atlantic multidecadal variability to the abrupt warming in Northeast Asia in the 1990s
Authors: Zhang Kaiwen , Zuo Zhiyan , Suarez-Gutierrez Laura , Bu Lulei
Published: January 2024

Northeast Asia experienced unprecedented abrupt warming in the 1990s since the last century. Based on a robust time series and rank frequency evaluation, the Max Planck Institute for Meteorology Grand Ensembles of CMIP5 (MPI-GE5), CMIP6 (MPI-GE6), EC-Earth3 and IPSL-CM6A-LR were identified as the models that best simulate the external forcing and internal variability in observations and represent observations most adequately. The negative-to-positive phase transition of the Atlantic multidecadal variability (AMV), combined with the external forcing, can explain 88% [60%−111%] of the 1990s warming. With prescribed anthropogenic emissions in the near future, a phase shift in the AMV to +2 (-2) standard deviation will amplify (weaken) the warming over Northeast Asia by 37% [29%−49%] (19% [15%−25%]). This highlights the importance of natural climate variability in Northeast Asia’s government decision-making and risk management, and emphasizes that only climate models with an adequate representation of forced warming can quantify these contributions correctly.
Integrative modeling uncovers p21-driven drug resistance and prioritizes therapies for PIK3CA-mutant breast cancer
Authors: Yip Hon Yan Kelvin , Shin Sung-Young , Chee Annabel , Ang Ching-Seng , Rossello Fernando J. , Wong Lee Hwa , Nguyen Lan K. , Papa Antonella
Published: January 2024

Utility of PI3Kα inhibitors like BYL719 is limited by the acquisition of genetic and non-genetic mechanisms of resistance which cause disease recurrence. Several combination therapies based on PI3K inhibition have been proposed, but a way to systematically prioritize them for breast cancer treatment is still missing. By integrating published and in-house studies, we have developed in silico models that quantitatively capture dynamics of PI3K signaling at the network-level under a BYL719-sensitive versus BYL719 resistant-cell state. Computational predictions show that signal rewiring to alternative components of the PI3K pathway promote resistance to BYL719 and identify PDK1 as the most effective co-target with PI3Kα rescuing sensitivity of resistant cells to BYL719. To explore whether PI3K pathway-independent mechanisms further contribute to BYL719 resistance, we performed phosphoproteomics and found that selection of high levels of the cell cycle regulator p21 unexpectedly promoted drug resistance in T47D cells. Functionally, high p21 levels favored repair of BYL719-induced DNA damage and bypass of the associated cellular senescence. Importantly, targeted inhibition of the check-point inhibitor CHK1 with MK-8776 effectively caused death of p21-high T47D cells, thus establishing a new vulnerability of BYL719-resistant breast cancer cells. Together, our integrated studies uncover hidden molecular mediators causing resistance to PI3Kα inhibition and provide a framework to prioritize combination therapies for PI3K-mutant breast cancer.
Molecular characterization of Fusarium venenatum-based microbial protein in animal models of obesity using multi-omics analysis
Authors: Lee Daniel Junpyo , Kang An Na , Lee Junbeom , Kwak Min-Jin , Mun Daye , Lee Daseul , Oh Sangnam , Kim Younghoon
Published: January 2024

Microbial protein, produced by fermentation of Fusarium venenatum is a promising candidate alternative protein source. Previous study has demonstrated its ability to improve hyperlipidemia in rats, yet the related mechanism remains unclear. In this study, we aimed to evaluate the potential of F. venenatum as an alternative protein source and its impact on lipid metabolism using multi-omics analysis. Initial experiments with Caenorhabditis elegans revealed that F. venenatum enhanced longevity, improved immune responses, and reduced lipid metabolism by downregulating fat synthesis-related genes. Subsequently, we conducted experiments with mice on a high-fat diet to confirm the anti-obesity effects of F. venenatum. The groups fed F. venenatum showed improved lipid profiles and reduced hepatic fat accumulation. Furthermore, fecal metabolomic analysis showed higher excretion of primary bile acid and cholesterol in the groups fed F. venenatum which might lead to a decrease in lipid digestion and hepatic fat accumulation. Collectively, this series of experiments revealed the potential of F. venenatum as a sustainable alternative protein and its application as an anti-obesity supplement.
Peripheral nerve regeneration following scaffold-free conduit transplant of autologous dermal fibroblasts: a non-randomised safety and feasibility trial
Authors: Ikeguchi Ryosuke , Aoyama Tomoki , Noguchi Takashi , Ushimaru Mika , Amino Yoko , Nakakura Akiyoshi , Matsuyama Noriko , Yoshida Shiori , Nagai-Tanima Momoko , Matsui Keiko , Arai Yasuyuki , Torii Yoko , Miyazaki Yudai , Akieda Shizuka , Matsuda Shuichi
Published: January 2024

Background

The use of Bio 3D nerve conduits is a promising approach for peripheral nerve reconstruction. This study aimed to assess their safety in three patients with peripheral nerve defects in their hands.

Methods

We describe a single institution, non-blinded, non-randomised control trial conducted at Kyoto University Hospital. Eligibility criteria included severed peripheral nerve injuries or a defect in the region distal to the wrist joint not caused by a congenital anomaly; a defect with a length of ≤20 mm in a nerve with a diameter ≤2 mm; failed results of sensory functional tests; ability to register in the protocol within 6 months from the day of injury; refusal of artificial nerve or autologous nerve transplantation; age 20–60 years; and willingness to participate and provide informed written consent. Six weeks before transplantation, skin was harvested, dermal fibroblasts were isolated and expanded, and Bio 3D nerve conduits were created using a Bio 3D printer. Bio 3D nerve conduits were transplanted into the patients’ nerve defects. The safety of Bio 3D nerve conduits in patients with a peripheral nerve injury in the distal part of the wrist joint were assessed over a 48-week period after transplantation.

Results

No adverse events related to the use of Bio 3D nerve conduits were observed in any patient, and all three patients completed the trial.

Conclusions

Bio 3D nerve conduits were successfully used for clinical nerve reconstruction without adverse events and are a possible treatment option for peripheral nerve injuries.
Improving the geographical origin classification of Radix glycyrrhizae (licorice) through hyperspectral imaging assisted by U-Net fine structure recognition
Authors: Zhang Hui , Pan YiXia , Chen Yuan , Zhang HongXu , Xie JianHui , Gong XingChu , Zhu JieQiang , Yan JiZhong
Published: January 2024

Collecting hyperspectral data of licorice from different origins, processing the data in three methods, and using multiple classifiers for origin classification, the results showed that the U-Net method could effectively improve the accuracy of origin classification.
A porous and photoactive Ti-MOF based on a novel tetranuclear [Ti2Tb2] cluster
Authors: Yao Qingxia , Pan Xuze , Si Xuezhen , Wang Xin , Zhang Xiaoying , Hou Jinle , Su Jie , Qiu Yi , Li Jun
Published: January 2024

A robust and porous Ti-MOF (LCU-505) has been synthesized based on a tetranuclear [Ti2Tb2] cluster. LCU-505 demonstrates an n-type semiconductor behavior and good photocatalytic activity in the degradation of organic dyes.
A portable polymeric electrochromism-based visual biosensing device with distance readout
Authors: Feng Xujing , Ding Lijun , Zou Yi , Heng Huadong , Di Kezuo , Shao Zhiying , Hao Nan , Wang Kun
Published: January 2024

A schematic diagram of the working mechanism of a distance readout biosensing device.
A computational study of a light-driven artificial device: a third generation rotational photo-molecular motor in dilute solutions
Authors: Zazza Costantino , Borocci Stefano , Sanna Nico
Published: January 2024

A third-generation artificial photo-molecular motor, featuring two photo-switchable rotating moieties in connection with a pseudoasymmetric molecular centre, is investigated by combining QM algorithms with classical MD propagators.
An α-benzithiazolyl 3-pyrrolyl BODIPY probe for ratiometric selective sensing of cyanide ions and bioimaging studies
Authors: Behera Kanhu Charan , Mohanty Roshnara , Ravikanth Mangalampalli
Published: January 2024

A simple chromo-fluorogenic probe, α-benzithiazolyl 3-pyrrolyl BODIPY, was synthesized and its use as a selective chemodosimetric sensor for CN− ions is demonstrated.
Exploration of biochemical reactivity with a QM/MM growing string method
Authors: McFarlane Neil R. , Harvey Jeremy N.
Published: January 2024

This work highlights a novel method for obtaining QM/MM reaction pathways which are of high-quality, quickly obtainable, and require minimal user intervention. Testing for the Claisen rearrangement in chorismate mutase shows the value of the method.
Wolfium bonds in homodimers of MX4Y (M = Mo, W; X = F, Cl, Br; Y = O, S, Se)
Authors: Michalczyk Mariusz , Zierkiewicz Wiktor , Scheiner Steve
Published: January 2024

The wolfium bond is a recently described noncovalent interaction in which metals belonging to group 6 act as electron acceptors.
Tunability of electronic properties in the 2D MoS2/α-tellurene/WS2 heterotrilayer via biaxial strain and electric field
Authors: Zhang Wenli , Ma Zhuang , Wang Jing , Shao Bin , Zuo Xu
Published: January 2024

In the MoS2/WS2/α-Te heterotrilayer, a portion of the electrons in the α-Te layer can overcome the barrier and transfer to the MoS2 layer, thereby facilitating the separation of photogenerated electron–hole pairs and prolonging the carrier lifetime.
Enhancing the durability of Pt nanoparticles for water electrolysis using ultrathin SiO2 layers
Authors: Li Ming , Saedy Saeed , Fu Shilong , Stellema Teise , Kortlever Ruud , van Ommen J. Ruud
Published: January 2024

Using ALD to coat the Pt/CB electrocatalysts with an ultrathin layer of SiO2 can strongly reduce the Pt agglomeration and detachment during hydrogen evolution reaction in acidic conditions.
Iron complexes supported by silyl-NHC chelate ligands: synthesis and use for double hydroboration of nitriles
Authors: Komuro Takashi , Hayasaka Kohei , Takahashi Kasumi , Ishiwata Nozomu , Yamauchi Kota , Tobita Hiromi , Hashimoto Hisako
Published: January 2024

Iron complexes with newly designed silyl-NHC bidentate ligands showed high performance in the catalytic double hydroboration of nitriles to produce N,N-bis(boryl)amines.
Enhancing dye degradation using a novel cobalt metal–organic framework as a peroxymonosulfate activator
Authors: Li Tuotuo , Omoniyi Ahmed Olalekan , Wang Yuliang , Hu Xiaoli , Su Zhongmin
Published: January 2024

A novel cobalt metal–organic framework catalyst was synthesized and used to activate PMS for the degradation of two dyes in aqueous solution. The catalyst demonstrated excellent effectiveness in catalyzing the degradation process.
Correlating hydrogen evolution and zinc deposition/dissolution kinetics to the cyclability of metallic zinc electrodes
Authors: Yang Huijun , Yang Yang , Yang Wuhai , Wu Gang , Zhu Ruijie
Published: January 2024

We correlate the Zn plating/stripping cyclability with the kinetics of hydrogen evolution. The pronounced hydrogen evolution kinetics and asymmetric Zn plating/stripping kinetics explain the poor Zn reversibility at low current density.
Heterogeneous interactions and transformations of dibasic esters with indoor relevant surfaces
Authors: Deeleepojananan Cholaphan , Zhou Jinxu , Grassian Vicki H.
Published: January 2024

Dibasic esters, indoor air pollutants emitted from furniture coatings, readily adsorb to surfaces thus initially decreasing their gas phase concentrations but then slowly desorb leading to possible long term exposure.
Tunable product selectivity on demand: a mechanism-guided Lewis acid co-catalyst for CO2 electroreduction to ethylene glycol
Authors: Li Yifei , Calvinho Karin U. D. , Dhiman Mahak , Laursen Anders B. , Gu Hengfei , Santorelli Dominick , Clifford Zachary , Dismukes G. Charles
Published: January 2024

This work illustrates the feasibility of using Lewis acid/base co-catalysts to change the established chemical reaction mechanism of an electrocatalyst to form a new, chemically predictable, more valuable product in high yield.
Dissociative chemisorption of O2 on Al(111): dynamics on a potential energy surface computed with a non-self-consistent screened hybrid density functional approach
Authors: van Bree Robert A. B. , Gerrits Nick , Kroes Geert-Jan
Published: January 2024

Non-SCF hybrid DFT reaction probabilities reproduce SCF results with near-chemical accuracy; non-SCF reaction barriers are higher. Computation time is reduced by more than an order of magnitude going from an SCF to non-SCF hybrid.
EGCG oxidation-derived polymers induce apoptosis in digestive tract cancer cells via regulating the renin–angiotensin system
Authors: Yang Mingchuan , Wu Ximing , He Yufeng , Li Xiuli , Yang Lumin , Song Tingting , Wang Fuming , Yang Chung S. , Zhang Jinsong
Published: January 2024

The EGCG polymers bind onto the cell surface and regulate multiple RAS components by reacting with the sulfhydryl groups on the ectodomains of transmembrane proteins, resulting in the apoptosis of CaCo2 cells.
The antioxidant strain Lactiplantibacillus plantarum AS21 and Clostridium butyricum ameliorate DSS-induced colitis in mice by remodeling the assembly of intestinal microbiota and improving gut functions
Authors: Li Wenyuan , Zhang Ying , Chen Mengyan , Guo Xusheng , Ding Zitong
Published: January 2024

Probiotics are known for their beneficial effects on improving intestinal function by alleviating the gut microbial diversity.
Selective neodymium recovery from model permanent magnets using cost-effective organic acid systems
Authors: Pozo-Gonzalo Cristina , Golmohammadzadeh Rabeeh , Myekhlai Munkhshur , Bastos Henrique , Deacon Glen B. , Somers Anthony E.
Published: January 2024

Simple and cost-effective mixture containing acetic acid to selective dissolve Nd over Fe from their corresponding oxides.
Natural polyphenolic nanodot-knotted conductive hydrogels for flexible wearable sensors
Authors: Yang Peng , Zhang Jianhua , Zhang Rong , Duan Gaigai , Li Yiwen , Li Zhan
Published: January 2024

Environmentally friendly and adaptable natural polyphenol/Fe3+ nanodots as nanoreactors to efficiently fabricate conductive hydrogels for sensors.
Theoretical investigation of carbon dioxide adsorption on MgH2 with a cobalt catalyst
Authors: Rozas Sara , Gennari Fabiana C. , Atilhan Mert , Bol Alfredo , Aparicio Santiago
Published: January 2024

CO2 adsorption mechanisms were investigated on an MgH2 substrate using CO2 activation. Cobalt catalyst enhanced CO2 chemical adsorption on top of Co SAC, while non-catalysed MgH2 induced CO2 physisorption on top of MgH2 interatomic cavities.
Vibrational manipulation of dry granular materials in lab-on-a-chip devices
Authors: Hui Timothy C. , Zhang Xiaolin , Adiga Dhruva , Miller Gregory H. , Ristenpart William D.
Published: January 2024

We present vibrational techniques to pump, mix, and separate dry granular materials using multifrequency vibrations applied to a solid substrate with a standard audio system.
Influence of cellulose nanocrystal surface chemistry and dispersion quality on latex nanocomposite stability, film formation and adhesive properties
Authors: Antoniw Julia M. , Gabriel Vida A. , Kiriakou Michael V. , Dubé Marc A. , Cunningham Michael F. , Cranston Emily D.
Published: January 2024

The different surface functional groups on carboxylated and sulfated cellulose nanocrystals (CNCs) affect the latex CNC–polymer interactions.
Chemical recycling of bromine-terminated polymers synthesized by ATRP
Authors: Mountaki Stella Afroditi , Whitfield Richard , Parkatzidis Kostas , Antonopoulou Maria-Nefeli , Truong Nghia P. , Anastasaki Athina
Published: January 2024

Efficient, fast and versatile depolymerization of bromine-terminated polymers.
N-Arylsulfonamide-based adenosine analogues to target RNA cap N7-methyltransferase nsp14 of SARS-CoV-2
Authors: Ahmed-Belkacem Rostom , Troussier Joris , Delpal Adrien , Canard Bruno , Vasseur Jean-Jacques , Decroly Etienne , Debart Françoise
Published: January 2024

SAH-derived bisubstrates of SARS-CoV-2 cap RNA N7-methyltransferase were synthesized, and two adenosines with an N-arylsulfonamide core attached by an N-ethylthioether linker proved to be effective inhibitors in the submicromolar range.
Metabolomics approach to understand molecular mechanisms involved in fungal pathogen–citrus pathosystems
Authors: Silva Evandro , Dantas Rodolfo , Barbosa Júlio César , Berlinck Roberto G. S. , Fill Taicia
Published: January 2024

This review article communicates the integration of metabolomics and genomics approaches to unravel the citrus host–pathogen interaction.
Open-tubular trap columns: towards simple and robust liquid chromatography separations for single-cell proteomics
Authors: Webber Kei G. I. , Huang Siqi , Truong Thy , Heninger Jacob L. , Gregus Michal , Ivanov Alexander R. , Kelly Ryan T.
Published: January 2024

PLOTrap combines the sample loop with the trap column for efficient nanoflow liquid chromatography sample cleanup and injection.
New conjugated carbazole derivatives: synthesis and photophysical properties catalysed by Pd–Cu@rGO
Authors: Bhagyalakshmi Vadla , Indira Meeniga , Banu Shaik Farheen , Venkateswarlu Derangula , Prasad Vasikarla Kamala , Sarma Loka Subramanyam , Reddy Cirandur Suresh , Reddy Peddiahgari Vasu Govardhana
Published: January 2024

Different wt% of Pd@rGO, Pd–Cu@rGO and Pd–Ni@rGO catalysts were prepared from a one-pot wet chemical method for the synthesis of various conjugated carbazole derivatives via Suzuki–Miyaura cross-coupling reaction and their photophysical properties were screened.
Detection of fluoride ions using carbon quantum dots derived from coal washery rejects via an on–off–on fluorescence mechanism: a smartphone-based image-processing and machine learning approach
Authors: Boruah Anusuya , Rajbonshi Akhil , Roy Kallol , Saikia Binoy K
Published: January 2024

An on–off–on fluorescence process-based fluoride ion sensor is developed by using highly fluorescent carbon quantum dots (CQDs) derived from coal washery rejects/waste coal (CWRs) and demonstrated through smartphone.
A disposable electrochemical caffeine sensor based on a screen-printed electrode modified with a copper-metal organic framework and functionalized multi-walled carbon nanotube nanocomposite
Authors: Saraban Muktinan , Numnuam Apon , Nontipichet Natha , Kangkamano Tawatchai , Thavarungkul Panote , Kanatharana Proespichaya , Khumngern Suntisak
Published: January 2024

A novel portable caffeine sensor was developed based on a copper-based metal–organic framework and multi-walled carbon nanotube nanocomposite which significantly increased the active surface area and conductivity of the electrode.