Search

The ability to predict how amino acid changes affect proteins has a wide range of applications including in disease variant classification and protein engineering. Many existing methods focus on learning from patterns found in either protein sequences or protein structures. Here, we present a method for integrating information from sequence and structure in a single model that we term SSEmb (Sequence Structure Embedding). SSEmb combines a graph representation for the protein structure with a transformer model for processing multiple sequence alignments. We show that by integrating both types of information we obtain a variant effect prediction model that is robust when sequence information is scarce. We also show that SSEmb learns embeddings of the sequence and structure that are useful for other downstream tasks such as to predict protein-protein binding sites. We envisage that SSEmb may be useful both for variant effect predictions and as a representation for learning to predict protein properties that depend on sequence and structure. SSEmb is a multi-modal machine learning model that predicts how changes in a protein's amino acid sequence affect its function by combining information from a multiple sequence alignment and the three-dimensional structure. [ABSTRACT FROM AUTHOR]

Gender equality represents a priority goal of the 2030 Agenda for Sustainable Development. Women everywhere run significant businesses, generating positive impacts on society. However, they still face numerous obstacles to starting and sustaining entrepreneurial activities. Extant literature, while increasingly acknowledging the importance of women's entrepreneurship, often overlooks the nuanced differences between aspirant and experienced female entrepreneurs. This study aims to address this gap by adopting a micro perspective and examining the commonalities and differences in the drivers and barriers to entrepreneurship among aspirant and experienced women entrepreneurs in Italy. Through semi-structured interviews conducted between September and December 2022, this exploratory study sheds light on the factors influencing women's entrepreneurial endeavors in a developed economy. We identified seven main themes: knowledge as gap for both, the role of technology, external support, socio-cultural background, network ties, territory concern, and personal dimension. Findings underscore the importance of understanding diverse backgrounds, motivations, and challenges faced by women entrepreneurs, offering insights for academic research. While at a general level factors and barriers are similar, at a micro level there are differences that could jeopardize both the success of this path in the start-up phase and its survival in the long term. The study also offers valuable practical implications by highlighting that women entrepreneurs should focus on idea validation, financial resources, networking, knowledge, and cultural stereotypes. At a policy level, tailored support strategies are recommended, including streamlined funding application processes and targeted training initiatives as well as measures to reduce socio-cultural barriers. [ABSTRACT FROM AUTHOR]

Developing resistance to cancer treatments is a major challenge, often leading to disease recurrence and metastasis. Understanding the underlying mechanisms of therapeutic resistance is critical for developing effective strategies. O-GlcNAcylation, a post-translational modification that adds GlcNAc from the donor UDP-GlcNAc to serine and threonine residues of proteins, plays a crucial role in regulating protein function and cellular signaling, which are frequently dysregulated in cancer. Similarly, ubiquitination, which involves the attachment of ubiquitin to to proteins, is crucial for protein degradation, cell cycle control, and DNA repair. The interplay between O-GlcNAcylation and ubiquitination is associated with cancer progression and resistance to treatment. This review discusses recent discoveries regarding the roles of O-GlcNAcylation and ubiquitination in cancer resistance, their interactions, and potential mechanisms. It also explores how targeting these pathways may provide new opportunities to overcome cancer treatment resistance in cancer, offering fresh insights and directions for research and therapeutic development. [ABSTRACT FROM AUTHOR]

Introduction: Long working hours are likely associated with the decreased of kidney function, while physical activity (PA) was linked to improvements in kidney function. However, whether PA can offset the negative impact of long working hours on kidney function was unclear, which is the focus of this study. Methods: A cross-sectional study was conducted. Three approaches were adopted to distinguish the association between long working hours and regular working hours. Moderate to vigorous physical activity (PA) was assessed by a structured questionnaire. eGFR and chronic kidney disease (CKD) or not were utilized to evaluate the kidney function. Linear and logistic regression analyses were conducted to assess the association between weekly working hours, PA, and kidney function. Results: A total of 18,431 adults were enrolled in this study, including 9981 males (54.2%) and 8450 females (45.8%). The average eGFR was (99.54 ± 17.55 mL/min/1.73m2). The people worked more than 40 h/wk (98.89 ± 17.06 mL/min/1.73 m2) had lower eGFR compared to those worked less than 40 h/wk (99.93 ± 17.83 mL/min/1.73 m2) (p < 0.05). Individuals working longer hours exhibited lower eGFR (b = -0.772, 95% CI: -1.241, -0.303, for > 40 h/wk compared to working = 40 h/wk). Engagement in moderate to vigorous PA was associated with higher eGFR values (b = 1.159, 95% CI: 0.699, 1.619) compared to low PA (< 150 minutes/wk), but this association did not reach statistical significance for the prevalence of CKD. Furthermore, PA was insufficient to reverse the decline of eGFR related to prolonged working hours. Discussion: Prolonged working hours were associated with a decline in eGFR, while PA was found to have a protective effect on kidney function. However, PA alone may not fully mitigate the negative impact of prolonged working hours on renal health. More robust measures to protect renal function should be implemented to mitigate the damage caused by prolonged working hours. [ABSTRACT FROM AUTHOR]

Great importance is attached to physical exercise and students' cognitive development, yet the precise mechanism linking the time duration of physical activities or sports with adolescents' cognitive development remains inconclusive. Based on the two-wave panel data of China Education Panel Survey (CEPS), this paper empirically examines the impact of daily physical exercise duration on junior middle school students' cognitive abilities, by using the two-way fixed-effect estimation. The findings reveal a nonlinear relationship, specifically an inverted "U"-shaped pattern, between daily time length of physical activities or sports and students' cognitive performance. The cognitive benefits of time investment in physical activities or sports reach the peak at approximately 0.829 h (equivalent to 50 min) per day among the teenagers in China. Furthermore, the daily time allocated to physical activities or sports affects students' cognitive performance differentially, students attending rural schools were rewarded more progressively, students of poorer physical fitness and those in good shape did not show discernible between-group differences. This study shades light on educational governance and time management, urging school administrators, parents and students to optimize the efficiency and utility of time resource invested in sports activities. [ABSTRACT FROM AUTHOR]

Patients with gastric cancer (GC) are more susceptible to coronavirus disease 2019 (COVID-19), which further worsens their already challenging prognosis. However, there are no effective treatment options for these patients. Lentinan is a potent bioactive component with antiviral and antitumor effects. We hypothesized that lentinan might exert powerful pharmacological effects in patients with GC and COVID-19. In this study, a prognostic model of patients with GC/COVID-19 was constructed and used to apply a network pharmacology approach to reveal biological functions, drug targets, and molecular mechanisms of the action of lentinan against GC/COVID-19. Clinical analysis revealed key prognostic genes in patients with GC/COVID-19. The results of network pharmacology analysis suggested that the therapeutic effect of lentinan on GC/COVID-19 mainly involves the modulation of several neutrophil-related biological processes, as well as the nucleotide-binding and oligomerization domain-like receptor and interleukin-17 signaling pathways. In addition, C-X-C motif chemokine ligand 8, vascular endothelial growth factor A, ribonuclease 3, and F2 were identified as key genes of lentinan against GC/COVID-19. Key prognostic genes were identified in patients with GC/COVID-19 through the construction of a prognostic model. Pharmacological functions and signaling pathways of lentinan against GC/COVID-19 were revealed. These included the regulation of neutrophils and NOD-like receptor signaling pathways. The findings provide the first published evidence of the potential value of lentinan as a complementary therapy for GC/COVID-19. [ABSTRACT FROM AUTHOR]

Liquid nitrogen (LN2) fracturing has various advantages, such as low reservoir damage, minimal environmental impact, and excellent permeability. In this study, the cracking pattern and damage evolution characteristics of bedded coal subjected to LN2 fracturing were investigated. The deterioration features of the mechanical parameters and failure mechanisms were examined in a comparable manner using Brazilian splitting tests. Additionally, the damage characteristics of bedded coal during LN2 fracturing were explored. The results indicated that LN2 cooling promoted the development of thermal cracks, consequently reducing the effective bearing capacity of the coal. Randomly distributed thermal cracks actively contributed to macroscopic crack propagation, increasing the proportion of shear cracks and the complexity of the fracture surface. Different bedding angles led to distinct failure modes, significantly impacting the proportion of shear cracks and the fracture surface complexity. Moreover, the bedding planes constantly influenced the propagation direction of the fracturing cracks, resulting in a macroscopic damage zone that expanded preferentially at the weak bedding planes with the borehole at the center. With increasing bedding angles, both the degree and rate of damage of coal decreased sequentially. Consequently, it was feasible to employ LN2 fracturing in low-permeability reservoirs along the bedding planes, facilitating swift and efficient reservoir fracturing. [ABSTRACT FROM AUTHOR]

Objectives: Neurons and glial cells are the main functional and structural elements of the brain, and the former depends on the latter for their nutritional, functional and structural organization, as well as for their energy maintenance. Methods: Glucose is the main metabolic source that fulfills energetic demands, either by direct anaplerosis or through its conversion to metabolic intermediates. Development of some neurodegenerative diseases have been related with modifications in the expression and/or function of glial glucose transporters, which might cause physiological and/or pathological disturbances of brain metabolism. In the present contribution, we summarized the experimental findings that describe the exquisite adjustment in expression and function of glial glucose transporters from physiologic to pathologic metabolism, and its relevance to neurodegenerative diseases. Results: A exhaustive literature review was done in order to gain insight into the role of brain energetics in neurodegenerative disease. This study made evident a critical involvement of glucose transporters and thus brain energetics in the development of neurodegenerative diseases. Discussion: An exquisite adjustment in the expression and function of glial glucose transporters from physiologic to pathologic metabolism is a biochemical signature of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Food Safety & Quality is the property of Journal of Food Safety & Quality Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cutaneous papillomatosis occurs as benign tumoral skin lesions in cattle. Although this condition is most commonly observed in young animals, it can occur in cattle of any age. Although tumor necrosis factor alpha, high mobility group box-1 protein, myxovirus resistance protein-1 have been investigated in various tumoral conditions in human medicine, the relationship between these markers and other hematological indices have not been investigated in bovine papillomatosis with benign tumoral lesions. The purpose of the study is to determine the levels of these markers and their relationship with each other and with hematological indices. The study comprised two groups: the bovine papillomatosis (BP) group, consisting of animals with papillomatosis, and the control group, consisting of healthy animals. Each group consisted of 10 animals of different breeds and genders with an age of 1-2 years. In the BP group, there were significant differences in total leukocyte count, neutrophil count, monocyte count, and neutrophil-lymphocyte ratio values, which were higher, and lymphocyte-monocyte ratio values, which were lower. The levels of high mobility group box-1 protein, myxovirus resistance protein-1, and tumor necrosis factor alpha were significantly higher in the BP group compared to the control group. In conclusion, this study showed that there were significant differences in hematological, inflammation and tumor markers in cutaneous papillomatosis. [ABSTRACT FROM AUTHOR]

Objective of this study is to evaluate the reliability and validity of the DSSCM based on a cross-sectional survey. Methods: The development of DSSCM was based on the traditional Chinese medicine (TCM) theory, expert consensus and clinical investigations. Participants were recruited from Guangdong Provincial Hospital of Chinese Medicine and Guangzhou Cadre Health Management Center in Guangdong Province, China. All participants completed the baseline questionnaire and DSSCM. The reliability of the DSSCM was evaluated by internal consistency reliability and test–retest reliability. The factor structure was tested with confirmatory factor analysis (CFA), while discriminant validity was evaluated by calculating the difference between the total score of the DSSCM and its four dimensions for participants with or without dampness syndrome. We used a clinician's diagnosis of dampness syndrome as a criterion to evaluate the criterion validity. Multivariate regression analysis was used to analyze the associations among gender, age, height, and weight and dampness syndrome. Results: A total of 880 participants were enrolled for psychometric validation and 869 participants were included in the final analyses after exclusion. The mean age of the participants was 42.62± 12.86 years. The Cronbach's alpha coefficients for the four dimensions of the DSSCM were 0.809, 0.891, 0.816 and 0.780. The ICCs for the four dimensions of the DSSCM were 0.806, 0.674, 0.780 and 0.760. For validity, the results showed that the DSSCM had good content validity, discriminant validity and criterion validity. For the CFA, the root mean square error of approximation (RMSEA) was 0.091; the standardized root mean square residual (SRMR) was 0.074; the comparative fit index (CFI) was 0.766; and the Tucker–Lewis index (TLI) was 0.745. Weight was found to be associated with the total scores of the DSSCM and its three dimensions. Conclusion: The DSSCM has good reliability and validity to support its use as a tool for assessing the severity of dampness syndrome. This study provides empirical evidence for future updates to the DSSCM. [ABSTRACT FROM AUTHOR]

As a small molecule, hydrogen is colorless, odorless and lightest. Many studies conducted that hydrogen can protect almost every organ, including the brain, heart muscle, liver, small intestine, and lungs. To verify whether high concentrations of hydrogen (HCH) has anti-inflammatory and antioxidant activities on respiratory system, we product a systematic review and meta-analysis. We investigated MEDLINE-PubMed, Cochrane Library, ScienceDirect, Wiley and SpringerLink database and selected in vivo studies related to the anti-inflammatory or antioxidant effects of HCH in the lung diseases which were published until September 2023. We firstly identified 437 studies and only 12 met the inclusion criteria. They all conducted in rodents. The results showed that HCH had a positive effect on the reduction of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-4, IL-8, malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS); but there is no effect on IL-6, we speculated that may contribute to the test results for different body fluids and at different points in time. This meta-analysis discovered the protective effects on inflammation and oxidative stress, but whether there exists more effects on reduction of inflammatory and oxidant mediators needs to be further elucidated. [ABSTRACT FROM AUTHOR]

Tandem repeats (TRs) are genomic regions that tandemly change in repeat number, which are often multiallelic. Their characteristics and contributions to gene expression and quantitative traits in rice are largely unknown. Here, we survey rice TR variations based on 231 genome assemblies and the rice pan-genome graph. We identify 227,391 multiallelic TR loci, including 54,416 TR variations that are absent from the Nipponbare reference genome. Only 1/3 TR variations show strong linkage with nearby bi-allelic variants (SNPs, Indels and PAVs). Using 193 panicle and 202 leaf transcriptomic data, we reveal 485 and 511 TRs act as QTLs independently of other bi-allelic variations to nearby gene expression, respectively. Using plant height and grain width as examples, we identify and validate TRs contributions to rice agronomic trait variations. These findings would enhance our understanding of the functions of multiallelic variants and facilitate rice molecular breeding. Tandem repeats (TRs) have unique ability to drive a range of phenotype variations. Here, the authors survey rice TR variations based on 231 genome assemblies and the rice pan-genome graph, identify TR variations associated with expressed genes, and reveal expression TRs contributed to rice agronomic trait variations. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neurodegenerative disease, with symptoms appearing in the cerebral cortex and hippocampus. amyloid β peptide (Aβ) has been shown to deposit in the brain, causing oxidative stress and inflammation, leading to impaired memory and learning. Lactocaseibacillus fermentation can produce deglycosylated isoflavones with high physiological activity, which can scavenge free radicals, enhance total antioxidant capacity and inhibit oxidative inflammatory responses. Therefore, in this study, Lactocaseibacillus paracasei subsp. paracasei NTU101 (NTU101) fermented soybean milk and its extracts were used as test substances, and AD model rats were established by infusion of Aβ40 in the brain for 28 days, and the preventive and ameliorating effects of NTU 101 fermented soymilk were discussed. Effects of soymilk and unfermented soymilk on AD, and explore its effects on AD. Main functional ingredients. The results showed that deglycosylated isoflavones in NTU101 fermented soybean milk improved AD symptoms. Mechanisms of actions include the inhibition of oxidative inflammation; reduction in the expression of risk factors for tau protein and apo E protein production, the deposition of Aβ40 around the hippocampus, and the expression of TLR-2 and RAGE proteins in astrocytes and microglia; and improvement in the memory and learning ability. Key points: Lactocaseibacillus-fermented soybean milk improved memory and learning abilityof AD rat Deglycosylated isoflavones (genistein and daidzein) were the functional compounds Deglycosylated isoflavones repress Aβ40 deposition by inhibiting TLR 2 and RAGE [ABSTRACT FROM AUTHOR]

Recent work demonstrated that activation of spinal D1 and D5 dopamine receptors (D1/D5Rs) facilitates non-Hebbian long-term potentiation (LTP) at primary afferent synapses onto spinal projection neurons. However, the cellular localization of the D1/D5Rs driving non-Hebbian LTP in spinal nociceptive circuits remains unknown, and it is also unclear whether D1/D5R signaling must occur concurrently with sensory input in order to promote non-Hebbian LTP at these synapses. Here we investigate these issues using cell-type–selective knockdown of D1Rs or D5Rs from lamina I spinoparabrachial neurons, dorsal root ganglion (DRG) neurons, or astrocytes in adult mice of either sex using Cre recombinase-based genetic strategies. The LTP evoked by low-frequency stimulation of primary afferents in the presence of the selective D1/D5R agonist SKF82958 persisted following the knockdown of D1R or D5R in spinoparabrachial neurons, suggesting that postsynaptic D1/D5R signaling was dispensable for non-Hebbian plasticity at sensory synapses onto these key output neurons of the superficial dorsal horn (SDH). Similarly, the knockdown of D1Rs or D5Rs in DRG neurons failed to influence SKF82958-enabled LTP in lamina I projection neurons. In contrast, SKF82958-induced LTP was suppressed by the knockdown of D1R or D5R in spinal astrocytes. Furthermore, the data indicate that the activation of D1R/D5Rs in spinal astrocytes can either retroactively or proactively drive non-Hebbian LTP in spinoparabrachial neurons. Collectively, these results suggest that dopaminergic signaling in astrocytes can strongly promote activity-dependent LTP in the SDH, which is predicted to significantly enhance the amplification of ascending nociceptive transmission from the spinal cord to the brain. [ABSTRACT FROM AUTHOR]

Introduction: In the occurrence and development of heat stroke (HS), factors such as hyperthermia, ischemia and hypoxia are essential to the central nervous system (CNS) inflammatory response, but the main mechanism underlying CNS inflammation remains unclear. The aim of the study was to observe the polarization of microglia in response to heat-induced early nerve injury and to explore its possible mechanism of action. Material and methods: To establish a heatstroke animal model in Beagle dogs, 18 Beagle dogs were divided into control (group A) and experimental groups (group B, group C and group D) according to a random numbers table. The animals in the experimental groups were placed on an electric blanket of an animal body temperature maintaining apparatus. The temperature was set at 40 ±0.5°C, and the rectal temperature was monitored every 5 min until the target body temperature was reached. Once the target temperature was reached, the dogs were transferred to an environment of 26 ±0.5°C and 60 ±0.5% humidity. Western blot analysis was used to detect the expression of microglia-specific markers CD45, iNOS, arginase, and CD206 in normal and heat-damaged brain tissues at different time points (1 h, 6 h, 24 h). The expression of CD45 and arginase was further determined by co-localization with immunofluorescence. Results: CD45 and iNOS protein expression was detected in group A. The two protein markers in group B were significantly higher than those in group A (p < 0.05), and the protein markers in group C were still higher than those in group A (p < 0.05). There was no statistically significant difference among the animals in group A (p > 0.05). Arginase and CD206 protein expression was also detected in group A. Levels of the two protein markers in group B were higher than those in group A (p < 0.05), and the protein marker levels in group C were even higher than those in group A (p < 0.05). Further analysis of the two groups of protein markers in group D showed significantly higher levels than those in group A (p < 0.001). Immunofluorescence co-localization of CD45 and arginase showed significantly increased fluorescence density at 6 h and 24 h after thermal injury (p < 0.001). Conclusions: After heat-induced disease, microglia were found to be active in the brain tissues of dogs. The microglia activated in the early 1-6 h of CNS injury were mainly the M1 type, which were then converted to the M2 type after 6 h. The 24 h M2 type was dominant. The relationship between M1/M2 polarization trends and early brain injury in heat-induced disease may be a key to understanding CNS injury in heat-induced disease. [ABSTRACT FROM AUTHOR]

The 2022 MW6.7 Menyuan earthquake ruptured the western end of the Tianzhu seismic gap, providing an opportunity to study the regional seismogenic characteristics and seismic hazards. Here we use interferometric synthetic aperture radar (InSAR) and seismic data to study the mainshock rupture, early afterslip and the second largest aftershock of the 2022 Menyuan earthquake sequences. Our modeling results show that the mainshock ruptured the Lenglongling fault and the Tuolaishan fault with a maximum slip of ~3 m. Rapid postseismic transient deformation occurred at the center of the Lenglongling fault. Our afterslip modeling reveals that the majority of afterslip occurred in the deeper part of the Lenglongling fault. A high-angle conjugated faulting event is found at the middle section of the Lenglongling fault. We use the stress inversion to investigate the possible triggering mechanism of the conjugated rupture event. The results indicate the maximum principal stress direction is in ~222°, forming a ~22° angle between the conjugated fault of second largest aftershock and the mainshock. The calculated normal stress changes indicate the region is within a pull-apart stress field, which favors such a conjugated rupturing event. Our study will help understand the rupture behavior of such kind of conjugated fault in other regions. [ABSTRACT FROM AUTHOR]

Protein stability plays a crucial role in a variety of applications, such as food processing, therapeutics, and the identification of pathogenic mutations. Engineering campaigns commonly seek to improve protein stability, and there is a strong interest in streamlining these processes to enable rapid optimization of highly stabilized proteins with fewer iterations. In this work, we explore utilizing a mega-scale dataset to develop a protein language model optimized for stability prediction. ESMtherm is trained on the folding stability of 528k natural and de novo sequences derived from 461 protein domains and can accommodate deletions, insertions, and multiple-point mutations. We show that a protein language model can be fine-tuned to predict folding stability. ESMtherm performs reasonably on small protein domains and generalizes to sequences distal from the training set. Lastly, we discuss our model's limitations compared to other state-of-the-art methods in generalizing to larger protein scaffolds. Our results highlight the need for large-scale stability measurements on a diverse dataset that mirrors the distribution of sequence lengths commonly observed in nature. Author summary: Research in Professor Justin Siegel's lab focuses on discovering and engineering enzyme catalysis. His work follows a design-build-test cycle, integrating computational protein modeling with wet-lab experiments. Key areas of his research include de novo enzyme design, enzyme therapeutics for celiac disease, and applications in food and renewable energy. Additionally, his lab has developed the Design2Data program, a multi-year, multi-campus effort to curate a high-quality dataset of enzymatic activity and stability for beta-glucosidase. Under the supervision of Professor Justin Siegel, I am engaged in molecular modeling and machine learning in protein engineering. I have a background in molecular dynamics simulations for protein and cell membrane permeability estimation and in using the Rosetta molecular modeling suite for protein structure modeling and enzyme-substrate interaction. Current research topics include the prediction of mutational effects on protein functions and protein language models for functional prediction and protein design. [ABSTRACT FROM AUTHOR]

Pt2Ca nanoparticles with a mean size diameter of 6 nm can be prepared by heating K2PtCl6, CaH2, carbon black and KCl at 400–500 °C. A mechanism study suggests that the formation of the Pt2Ca phase at moderate temperature is enabled by the fast ion transport via the vacancies in the KCl–CaH2 solid solution. The Pt2Ca nanoparticles exhibit high performance for the oxygen reduction reaction in acid due to optimal adsorption energy of the oxygen intermediate. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammation markers have recently been identified as being associated with cardiac disorders. However, limited research has been conducted to estimate the pre-diagnostic associations between these markers and paroxysmal atrial fibrillation (PAF). Our aim is to identify potential biomarkers for early detection of PAF. Methods: 91 participants in the PAF group and 97 participants in the non-PAF group were included in this study. We investigated the correlations between three systemic inflammation markers, namely the systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), and PAF. Results: The proportion of patients with PAF gradually increased with increasing logSII, logSIRI, and logAISI tertiles. Compared to those in the lowest tertiles, the PAF risks in the highest logSII and logSIRI tertiles were 3.2-fold and 2.9-fold, respectively. Conversely, there was no significant correlation observed between logAISI and PAF risk within the highest tertile of logAISI. The restricted cubic splines (RCS) analysis revealed a non-linear relationship between the elevation of systemic inflammation markers and PAF risk. Specifically, the incidence of PAF is respectively increased by 56%, 95%, and 150% for each standard deviation increase in these variables. The ROC curve analysis of logSII, logSIRI and logAISI showed that they had AUC of 0.6, 0.7 and 0.6, respectively. It also demonstrated favorable sensitivity and specificity of these systemic inflammation markers in detecting the presence of PAF. Conclusions: In conclusion, our study reveals significant positive correlations between SII, SIRI, and AISI with the incidence of PAF. [ABSTRACT FROM AUTHOR]

Calcium (Ca2+) signaling plays a pivotal role in coordinating neural stem cell (NSC) proliferation across various cell cycle stages, regulating immediate early gene transcription, and governing processes like quiescence and cell division. Additionally, calcium signaling pathways are implicated in the initiation, progression, and therapeutic targeting of glioblastoma multiforme (GBM), particularly focusing on glioma stem cells (GSCs). Intracellular calcium levels are increased through the activation of channels, transporters, and calcium-binding proteins (CaBPs), which generate specific calcium signals characterized by spatial, temporal, and intensity profiles. Moreover, extracellular factors such as growth factors, neurotransmitters, and extracellular nucleotides modulate calcium levels to finely regulate NSC and GBM behavior. Calcium-associated proteins and ion channels like calcium release-activated (CRAC) channels and voltage-gated calcium channels play key roles in NSC proliferation and differentiation. Despite calcium's versatile and widespread role as a second messenger critical for regulating various cellular functions, the specific roles of calcium in stem cell niches, stem cell maintenance, and glioblastoma stem cells are still in early stages of exploration. This article aimed to provide a comprehensive and current understanding of the roles of calcium signaling in NSC behavior and interactions within their niche, which are critical for neurogenesis, brain repair mechanisms, and understanding age-related decline in stem cell function. Investigating the heterogeneity of GBM tumors resembling neurospheres and their similarity to neural stem cells (NSCs) highlights the critical involvement of calcium in governing cellular behaviors such as quiescence, proliferation, and migration. Furthermore, this manuscript illuminates various potential interventions targeting calcium channels and associated signaling pathways to mitigate GSC activities and hinder GBM recurrence, offering a promising avenue for developing novel therapeutic strategies against GBM. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Food Safety & Quality is the property of Journal of Food Safety & Quality Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Sichuan Mental Health is the property of Sichuan Mental Health Center and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Mycosystema is the property of Mycosystema Editorial Board and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In real applied fields such as clinical medicine, environmental sciences, psychology as well as economics, we often encounter the task of conducting statistical inference for longitudinal data with ordinal responses. The traditional methods of longitudinal data analysis are often inclined to model continuous responses, which are no longer suitable for such ordinal data. Logistic regression and probit regression are two considerable methods which are frequently used to model ordinal longitudinal responses. However, such modelling methods just depict the mean feature of latent outcome variable and may produce non-robust results when encountering nor-normal errors or outliers. As a proper alternative of mean regression models, composite quantile regression (CQR) method is usually employed to derive robust estimation. The target of this paper is to investigate the CQR estimation approach for ordinal latent longitudinal model. The joint Bayesian hierarchical model is established and a relative CQR estimation approach is suggested to conduct posterior inference for the considered model. Further, in longitudinal data modelling, excessive predictors may be brought into in the models which result in the decrease of the model prediction precision. Bayesian $ L_{1/2} $ L 1 / 2 regularized prior is incorporated into ordinal longitudinal CQR model to conduct variable selection simultaneously. Finally, simulation studies and two ordinal longitudinal data analysis are hired to illustrate the considered method. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Gerontologie und Geriatrie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Type 2 diabetes (T2D) is a polygenic metabolic disorder characterized by insulin resistance in peripheral tissues and impaired insulin secretion by the pancreas. While the decline in insulin production and secretion was previously attributed to apoptosis of insulin-producing b-cells, recent studies indicate that b-cell apoptosis rates are relatively low in diabetes. Instead, b-cells primarily undergo dedifferentiation, a process where they lose their specialized identity and transition into non-functional endocrine progenitor-like cells, ultimately leading to b-cell failure. The underlying mechanisms driving b-cell dedifferentiation remain elusive due to the intricate interplay of genetic factors and cellular stress. Understanding these mechanisms holds the potential to inform innovative therapeutic approaches aimed at reversing b-cell dedifferentiation in T2D. This review explores the proposed drivers of b-cell dedifferentiation leading to b-cell failure, and discusses current interventions capable of reversing this process, thus restoring b-cell identity and function. [ABSTRACT FROM AUTHOR]

Background: A rising population faces challenges with healing-impaired cutaneous wounds, often leading to physical disabilities. Adipose-derived stem cells (ASCs), specifically in the cell sheet format, have emerged as a promising remedy for impaired wound healing. Human platelet lysate (HPL) provides an attractive alternative to fetal bovine serum (FBS) for culturing clinical-grade ASCs. However, the potential of HPL sheets in promoting wound healing has not been fully investigated. This study aimed to explore the anti-fibrotic and pro-angiogenic capabilities of HPL-cultured ASC sheets and delve into the molecular mechanism. Methods: A rat burn model was utilized to evaluate the efficacy of HPL-cultured ASC sheets in promoting wound healing. ASC sheets were fabricated with HPL, and those with FBS were included for comparison. Various analyses were conducted to assess the impact of HPL sheets on wound healing. Histological examination of wound tissues provided insights into aspects such as wound closure, collagen deposition, and overall tissue regeneration. Immunofluorescence was employed to assess the presence and distribution of transplanted ASCs after treatment. Further in vitro studies were conducted to decipher the specific factors in HPL sheets contributing to angiogenesis. Results: HPL-cultured ASC sheets significantly accelerated wound closure, fostering ample and organized collagen deposition in the neo-dermis. Significantly more retained ASCs were observed in wound tissues treated with HPL sheets compared to the FBS counterparts. Moreover, HPL sheets mitigated macrophage recruitment and decreased subsequent wound tissue fibrosis in vivo. Immunohistochemistry also indicated enhanced angiogenesis in the HPL sheet group. The in vitro analyses showed upregulation of C–C motif chemokine ligand 5 (CCL5) and angiogenin in HPL sheets, including both gene expression and protein secretion. Culturing endothelial cells in the conditioned media compared to media supplemented with CCL5 or angiogenin suggested a correlation between CCL5 and the pro-angiogenic effect of HPL sheets. Additionally, through neutralizing antibody experiments, we further validated the crucial role of CCL5 in HPL sheet-mediated angiogenesis in vitro. Conclusions: The present study underscores CCL5 as an essential factor in the pro-angiogenic effect of HPL-cultured ASC sheets during the wound healing process. These findings highlight the potential of HPL-cultured ASC sheets as a promising therapeutic option for healing-impaired cutaneous wounds in clinical settings. Furthermore, the mechanism exploration yields valuable information for optimizing regenerative strategies with ASC products. Brief acknowledgment: This research was supported by the National Science and Technology Council, Taiwan (NSTC112-2321-B-002-018), National Taiwan University Hospital (111C-007), and E-Da Hospital-National Taiwan University Hospital Joint Research Program (111-EDN0001, 112-EDN0002). [ABSTRACT FROM AUTHOR]

Background: The C-type lectin family 18 (CLEC18) with lipid and glycan binding capabilities is important to metabolic regulation and innate immune responses against viral infection. However, human CLEC18 comprises three paralogous genes with highly similar sequences, making it challenging to distinguish genetic variations, expression patterns, and biological functions of individual CLEC18 paralogs. Additionally, the evolutionary relationship between human CLEC18 and its counterparts in other species remains unclear. Methods: To identify the sequence variation and evolutionary divergence of human CLEC18 paralogs, we conducted a comprehensive analysis using various resources, including human and non-human primate reference genome assemblies, human pangenome assemblies, and long-read-based whole-genome and -transcriptome sequencing datasets. Results: We uncovered paralogous sequence variants (PSVs) and polymorphic variants (PVs) of human CLEC18 proteins, and identified distinct signatures specific to each CLEC18 paralog. Furthermore, we unveiled a novel segmental duplication for human CLEC18A gene. By comparing CLEC18 across human and non-human primates, our research showed that the CLEC18 paralogy probably occurred in the common ancestor of human and closely related non-human primates, and the lipid-binding CAP/SCP/TAPS domain of CLEC18 is more diverse than its glycan-binding CTLD. Moreover, we found that certain amino acids alterations at variant positions are exclusive to human CLEC18 paralogs. Conclusions: Our findings offer a comprehensive profiling of the intricate variations and evolutionary characteristics of human CLEC18. [ABSTRACT FROM AUTHOR]

Epidemiological studies have unveiled a robust link between exposure to repetitive mild traumatic brain injury (r-mTBI) and elevated susceptibility to develop neurodegenerative disorders, notably chronic traumatic encephalopathy (CTE). The pathogenic lesion in CTE cases is characterized by the accumulation of hyperphosphorylated tau in neurons around small cerebral blood vessels which can be accompanied by astrocytes that contain phosphorylated tau, the latter termed tau astrogliopathy. However, the contribution of tau astrogliopathy to the pathobiology and functional consequences of r-mTBI/CTE or whether it is merely a consequence of aging remains unclear. We addressed these pivotal questions by utilizing a mouse model harboring tau-bearing astrocytes, GFAPP301L mice, subjected to our r-mTBI paradigm. Despite the fact that r-mTBI did not exacerbate tau astrogliopathy or general tauopathy, it increased phosphorylated tau in the area underneath the impact site. Additionally, gene ontology analysis of tau-bearing astrocytes following r-mTBI revealed profound alterations in key biological processes including immunological and mitochondrial bioenergetics. Moreover, gene array analysis of microdissected astrocytes accrued from stage IV CTE human brains revealed an immunosuppressed astroglial phenotype similar to tau-bearing astrocytes in the GFAPP301L model. Additionally, hippocampal reduction of proteins involved in water transport (AQP4) and glutamate homeostasis (GLT1) was found in the mouse model of tau astrogliopathy. Collectively, these findings reveal the importance of understanding tau astrogliopathy and its role in astroglial pathobiology under normal circumstances and following r-mTBI. The identified mechanisms using this GFAPP301L model may suggest targets for therapeutic interventions in r-mTBI pathogenesis in the context of CTE. [ABSTRACT FROM AUTHOR]

Background: Pneumonia poses a major global health challenge, necessitating accurate severity assessment tools. However, conventional scoring systems such as CURB-65 have inherent limitations. Machine learning (ML) offers a promising approach for prediction. We previously introduced the Blood Culture Prediction Index (BCPI) model, leveraging solely on complete blood count (CBC) and differential leukocyte count (DC), demonstrating its effectiveness in predicting bacteremia. Nevertheless, its potential in assessing pneumonia remains unexplored. Therefore, this study aims to compare the effectiveness of BCPI and CURB-65 in assessing pneumonia severity in an emergency department (ED) setting and develop an integrated ML model to enhance efficiency. Methods: This retrospective study was conducted at a 3400-bed tertiary medical center in Taiwan. Data from 9,352 patients with pneumonia in the ED between 2019 and 2021 were analyzed in this study. We utilized the BCPI model, which was trained on CBC/DC data, and computed CURB-65 scores for each patient to compare their prognosis prediction capabilities. Subsequently, we developed a novel Cox regression model to predict in-hospital mortality, integrating the BCPI model and CURB-65 scores, aiming to assess whether this integration enhances predictive performance. Results: The predictive performance of the BCPI model and CURB-65 score for the 30-day mortality rate in ED patients and the in-hospital mortality rate among admitted patients was comparable across all risk categories. However, the Cox regression model demonstrated an improved area under the ROC curve (AUC) of 0.713 than that of CURB-65 (0.668) for in-hospital mortality (p<0.001). In the lowest risk group (CURB-65=0), the Cox regression model outperformed CURB-65, with a significantly lower mortality rate (2.9% vs. 7.7%, p<0.001). Conclusions: The BCPI model, constructed using CBC/DC data and ML techniques, performs comparably to the widely utilized CURB-65 in predicting outcomes for patients with pneumonia in the ED. Furthermore, by integrating the CURB-65 score and BCPI model into a Cox regression model, we demonstrated improved prediction capabilities, particularly for low-risk patients. Given its simple parameters and easy training process, the Cox regression model may be a more effective prediction tool for classifying patients with pneumonia in the emergency room. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study was to evaluate the prevalence and the morphology of c-shaped root canal(s) in mandibular premolars using cone beam computed tomography (CBCT) images. Materials and Methods CBCT images of 1095 mandibular premolars were examined at coronal, middle, and apical levels of the root canals. The type, the level, and the position (buccal or lingual) of the c-shaped anatomy were recorded. Absolute counts and percentages of different groups and subgroups of C-shape morphologies were calculated. The Chi-square test was used to compare the prevalence of C-shaped morphology between mandibular first and second premolars. The Z-test for proportions in independent groups was used to analyze the differences in mandibular C-shaped premolar proportions between location (left and right side) and tooth (first or second premolars) (p=0.05). Results C-shaped root canal morphology was present in 44 teeth. The percentage of c-shaped morphologies was 6.9% and 1.6% in mandibular first and second premolars, respectively. Comparison of the first and the second premolars showed that C1 type (p=0.008) and C4b type (p=0.013) configurations are more common in the first premolars at the coronal level. In contrast, the C2 type configuration showed significantly higher prevalence in the second premolars (p=0.009). Additionally, the C4c type configuration was significantly frequent on the right premolars at the coronal level (p=0.038). Conclusion C-shape canal morphology is a rare but complex anatomic feature in mandibular premolars. Therefore, clinicians should be aware of this complex root canal anatomy for the success of endodontic treatment in mandibular premolar teeth. [ABSTRACT FROM AUTHOR]

Greenhouse gases (GHGs) emission has been growing for decades, that has resulted in serious environmental problems. Many researches have focused on production planning in supply chains that are primarily attributed to objectives of cost minimization and profit maximization. There has been limited research concentrated on emission of GHGs (e.g. CO 2 , N 2 O, CH 4 ) from industrial activities. The social concern of air pollution is the motivation towards the proposed study. In this study, we propose an optimization model for designing a sustainable supply chain management (SSCM) network that attempts to reduce carbon emission, improve social benefits and eventually improve customer experience. The optimization model is a multi objective mixed integer linear programming (MILP) formulation. The proposed model is a multi raw-material, multi-product, multi-period, multi-sites model that focuses on improving three dimensions of sustainability: viz. economic, environmental and social. Model performance is demonstrated through numerical experiments. The authors are currently working on solution algorithm for solving larger instances of the proposed model. [ABSTRACT FROM AUTHOR]

Background: Articular cartilage is a vital component of the joint, as it is frequently exposed to trauma and is affected by several conditions and diseases such as osteoarthritis and hemophilic arthropathy. Therefore, its evaluation and assessment are crucial. Magnetic resonance imaging (MRI) plays a critical role in its evaluation. With the recent advances in MRI imaging, multiple techniques and modalities allow both morphological and physiological evaluation of articular cartilage. Morphological methods allow the evaluation of articular cartilage structural integrity, and physiological methods allow the evaluation of chemical changes in its components even prior to degeneration. This aids in the early detection and improved assessment of articular cartilage pathology. Therefore, it permits a more accurate evaluation of patients with articular cartilage issues and defects, allowing for prompt treatment and high better quality of life. This article reviews recent and innovative MRI techniques and sequences for morphological and functional evaluation of the cartilage. Methods: A broad-based internet search, utilizing multiple academic search engines, Google Scholar, and PubMed, using the keywords for title and abstract. We found 17500 results and excluded 1700 papers from the title and abstract. Furthermore, papers emphasizing the imaging of specific peripheral joints without discussing the main techniques were excluded. Finally, our search yielded 15 articles highlighting the most recent imaging and evaluation techniques for articular cartilage. Recent advancements and new MRI techniques aid in elucidating the anatomical and physiological details of articular cartilage, allowing for the early detection and treatment of the articular cartilage. Conclusions: Multiple recent advances and new MRI techniques help better delineate the anatomical and physiological details of the articular cartilage, so early interference and treatment of cartilage defects. [ABSTRACT FROM AUTHOR]