bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening for thalassemia carriers among the Han population of childbearing age in Southwestern of China
Authors: Du Yepei , Zhou Cong , Wang Jing , Yang Yanting , Liu Hui
Published: April 2024

Purpose:

Thalassemia is a severe hereditary blood disorder that poses a significant threat to human health and leads to mortality and disability. It is one of the most prevalent monogenic diseases worldwide. The aim of this study was to analyze the molecular epidemiological data of individuals of childbearing age from the Han ethnic group with thalassemia in Southwest China and to explore the application of next-generation sequencing (NGS) technology in screening thalassemia carriers.

Methods:

The participants were Han males and females of childbearing age who sought medical advice at the West China Second University Hospital, Sichuan University from June 2022 to June 2023. We detected α- and β-thalassemia mutations using full-length capture of the thalassemia genes and NGS technology.

Results:

In a cohort of 1,093 participants, 130 thalassemia carriers were identified, with an overall detection rate of 11.89% (130/1,093). Among these, 0.91% (10/1,093) had mutations that could not be detected using traditional PCR techniques. The proportions of carriers with α-, β-, and α-complexed β-thalassemia gene mutations were 7.68% (84/1,093), 3.93% (43/1,093), and 0.27% (3/1,093), respectively. We identified a novel HBA2 c.166del variant that has not been previously reported.

Conclusion:

Using NGS technology, we found that the mutation-carrying rate of thalassemia genes was 11.89% in the Han population of childbearing age in Southwest China. Compared with the results of traditional PCR techniques, NGS detected an additional 0.91% (10/1,093) rare genetic variants. NGS technology should be utilized as the primary screening method for thalassemia carriers among Han nationality people of childbearing age in Southwest China.
Integrative analysis of the lncRNA-miRNA-mRNA interactions in smooth muscle cell phenotypic transitions
Authors: Mahajan Aatish , Hong Junyoung , Krukovets Irene , Shin Junchul , Tkachenko Svyatoslav , Espinosa-Diez Cristina , Owens Gary K. , Cherepanova Olga A.
Published: April 2024

Objectives: We previously found that the pluripotency factor OCT4 is reactivated in smooth muscle cells (SMC) in human and mouse atherosclerotic plaques and plays an atheroprotective role. Loss of OCT4 in SMC in vitro was associated with decreases in SMC migration. However, molecular mechanisms responsible for atheroprotective SMC-OCT4-dependent effects remain unknown.

Methods: Since studies in embryonic stem cells demonstrated that OCT4 regulates long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), making them candidates for OCT4 effect mediators, we applied an in vitro approach to investigate the interactions between OCT4-regulated lncRNAs, mRNAs, and miRNAs in SMC. We used OCT4 deficient mouse aortic SMC (MASMC) treated with the pro-atherogenic oxidized phospholipid POVPC, which, as we previously demonstrated, suppresses SMC contractile markers and induces SMC migration. Differential expression of lncRNAs, mRNAs, and miRNAs was obtained by lncRNA/mRNA expression array and small-RNA microarray. Long non-coding RNA to mRNA associations were predicted based on their genomic proximity and association with vascular diseases. Given a recently discovered crosstalk between miRNA and lncRNA, we also investigated the association of miRNAs with upregulated/downregulated lncRNA-mRNA pairs.

Results: POVPC treatment in SMC resulted in upregulating genes related to the axon guidance and focal adhesion pathways. Knockdown of Oct4 resulted in differential regulation of pathways associated with phagocytosis. Importantly, these results were consistent with our data showing that OCT4 deficiency attenuated POVPC-induced SMC migration and led to increased phagocytosis. Next, we identified several up- or downregulated lncRNA associated with upregulation of the specific mRNA unique for the OCT4 deficient SMC, including upregulation of ENSMUST00000140952-Hoxb5/6 and ENSMUST00000155531-Zfp652 along with downregulation of ENSMUST00000173605-Parp9 and, ENSMUST00000137236-Zmym1. Finally, we found that many of the downregulated miRNAs were associated with cell migration, including miR-196a-1 and miR-10a, targets of upregulated ENSMUST00000140952, and miR-155 and miR-122, targets of upregulated ENSMUST00000155531. Oppositely, the upregulated miRNAs were anti-migratory and pro-phagocytic, such as miR-10a/b and miR-15a/b, targets of downregulated ENSMUST00000173605, and miR-146a/b and miR-15b targets of ENSMUST00000137236.

Conclusion: Our integrative analyses of the lncRNA-miRNA-mRNA interactions in SMC indicated novel potential OCT4-dependent mechanisms that may play a role in SMC phenotypic transitions.
Evaluation of cytokine profiles related to Mycobacterium tuberculosis latent antigens using a whole-blood assay in the Philippines
Authors: Yasuda Ikkoh , Saludar Naomi Ruth D. , Sayo Ana Ria , Suzuki Shuichi , Yokoyama Akira , Ozeki Yuriko , Kobayashi Haruka , Nishiyama Akihito , Matsumoto Sohkichi , Cox Sharon E. , Tanaka Takeshi , Yamashita Yoshiro
Published: April 2024

Introduction

There is no useful method to discriminate between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB). This study aimed to investigate the potential of cytokine profiles to discriminate between LTBI and active PTB using whole-blood stimulation with Mycobacterium tuberculosis (MTB) antigens, including latency-associated antigens.

Materials and methods

Patients with active PTB, household contacts of active PTB patients and community exposure subjects were recruited in Manila, the Philippines. Peripheral blood was collected from the participants and used for whole-blood stimulation (WBS) with either the early secretory antigenic target and the 10-kDa culture filtrate protein (ESAT-6/CFP-10), Rv3879c or latency-associated MTB antigens, including mycobacterial DNA-binding protein 1 (MDP-1), α-crystallin (Acr) and heparin-binding hemagglutinin (HBHA). Multiple cytokine concentrations were analyzed using the Bio-Plex™ multiplex cytokine assay.

Results

A total of 78 participants consisting of 15 active PTB patients, 48 household contacts and 15 community exposure subjects were eligible. The MDP-1-specific IFN-γ level in the active PTB group was significantly lower than that in the household contact group (p < 0.001) and the community exposure group (p < 0.001). The Acr-specific TNF-α and IL-10 levels in the active PTB group were significantly higher than those in the household contact (TNF-α; p = 0.001, IL-10; p = 0.001) and community exposure (TNF-α; p < 0.001, IL-10; p = 0.01) groups. However, there was no significant difference in the ESAT-6/CFP-10-specific IFN-γ levels among the groups.

Conclusion

The patterns of cytokine profiles induced by latency-associated MTB antigens using WBS have the potential to discriminate between LTBI and active PTB. In particular, combinations of IFN-γ and MDP-1, TNF-α and Acr, and IL-10 and Acr are promising. This study provides the first demonstration of the utility of MDP-1-specific cytokine responses in WBS.
A novel web-based dynamic prognostic nomogram for gastric signet ring cell carcinoma: a multicenter population-based study
Authors: Jiang Yujuan , Hu Haitao , Shao Xinxin , Li Weikun , Lu Yiming , Liang Jianwei , Tian Yantao
Published: April 2024

Background

Gastric signet ring cell carcinoma (GSRCC) is a rare and highly malignant disease with a poor prognosis. To assess the overall survival (OS) and cancer-specific survival (CSS) of patients with GSRCC, prognostic nomograms were developed and validated using common clinical factors.

Methods

This retrospective cohort study included patients diagnosed with GSRCC between 2011 and 2018 from the National Cancer Center (n = 1453) and SEER databases (n = 2745). Prognostic nomograms were established by identifying independent prognostic factors using univariate and multivariate Cox regression analyses. The calibration curve and C-index were used to assess the predictions. The clinical usefulness of the survival prediction model was further evaluated using the DCA and ROC curves. The models were internally validated in the training cohort and externally validated in the validation cohort. Two web servers were created to make the nomogram easier to use.

Results

Patients with GSRCC were divided into training (n = 2938) and validation (n = 1260) cohorts. The nomograms incorporated six predictors: age, race, tumor site, tumor size, N stage, T stage, and AJCC stage. Excellent agreement was observed between the internal and exterior calibration plots for the GSRCC survival estimates. The C-index and area under the ROC curve were roughly greater than 0.7. Both nomograms had adequate clinical efficacy, as demonstrated by the DCA plots. Furthermore, we developed a dynamic web application utilizing the constructed nomograms available at https://jiangyujuan.shinyapps.io/OS-nomogram/ and https://jiangyujuan.shinyapps.io/DynNomapp-DFS/.

Conclusion

We developed web-based dynamic nomograms utilizing six independent prognostic variables that assist physicians in estimating the OS and CSS of patients with GSRCC.
Potential application mechanism of traditional Chinese medicine in treating immune checkpoint inhibitor-induced colitis
Authors: Wang Jing , Guo Ziyue , Shen Mengyi , Xie Qi , Xiang Hongjie
Published: April 2024

Cancer ranks among the foremost causes of mortality worldwide, posing a significant threat to human lives. The advent of tumor immunotherapy has substantially transformed the therapeutic landscape for numerous advanced malignancies, notably non-small cell lung cancer and melanoma. However, as immune checkpoint inhibitors (ICIs) are increasingly applied in clinical settings, a spectrum of undesired reactions, termed immune-related adverse events (irAEs), has emerged. These adverse reactions are associated with immunotherapy and can result in varying degrees of harm to the human body. Among these reactions, Immune checkpoint inhibitor-induced colitis (ICIIC) stands out as one of the most prevalent clinical adverse events. In contemporary times, traditional Chinese medicine (TCM) has demonstrated remarkable efficacy in addressing various maladies. Consequently, investigating the potential application and mechanisms of Chinese medicine in countering immune checkpoint inhibitor-induced colitis assumes significant importance in the treatment of this condition.
Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCM
Authors: Rong Dongyun , Su Yushen , Jia Dechao , Zeng Zhirui , Yang Yan , Wei Dalong , Lu Honguan , Cao Yu
Published: April 2024

Background

Skin Cutaneous Melanoma (SKCM) incidence is continually increasing, with chemotherapy and immunotherapy being among the most common cancer treatment modalities. This study aims to identify novel biomarkers for chemotherapy and immunotherapy response in SKCM and explore their association with oxidative stress.

Methods

Utilizing TCGA-SKCM RNA-seq data, we employed Weighted Gene Co-expression Network Analysis (WGCNA) and Protein-Protein Interaction (PPI) networks to identify six core genes. Gene co-expression analysis and immune-related analysis were conducted, and specific markers associated with oxidative stress were identified using Gene Set Variation Analysis (GSVA). Single-cell analysis revealed the expression patterns of Oxidative Stress-Associated Genes (OSAG) in the tumor microenvironment. TIDE analysis was employed to explore the association between immune therapy response and OSAG, while CIBERSORT was used to analyze the tumor immune microenvironment. The BEST database demonstrated the impact of the Oxidative Stress signaling pathway on chemotherapy drug resistance. Immunohistochemical staining and ROC curve evaluation were performed to assess the protein expression levels of core genes in SKCM and normal samples, with survival analysis utilized to determine their diagnostic value.

Results

We identified six central genes associated with SKCM metastasis, among which the expression of DSC2 and DSC3 involved in the oxidative stress pathway was closely related to immune cell infiltration. DSC2 influenced drug resistance in SKMC patients. Furthermore, downregulation of DSC2 and DSC3 expression enhanced the response of SKCM patients to immunotherapy.

Conclusion

This study identified two Oxidative Stress-Associated genes as novel biomarkers for SKCM. Additionally, targeting the oxidative stress pathway may serve as a new strategy in clinical practice to enhance SKCM chemotherapy and sensitivity.
FOXP3 full length splice variant is associated with kidney allograft tolerance
Authors: Saleh Qais W. , Mohammadnejad Afsaneh , Tepel Martin
Published: April 2024

Background

Progressive decline of allograft function leads to premature graft loss. Forkhead box P3 (FOXP3), a characteristic gene of T-regulatory cells, is known to be essential for auto-antigen tolerance. We assessed the hypothesis that low FOXP3 mRNA splice variant levels in peripheral blood cells early after transplantation are associated with progressive allograft injury.

Methods

Blood samples were prospectively collected from 333 incident kidney transplant recipients on the first and 29th postoperative day. We used quantitative polymerase chain reaction to determine transcripts of 3 isotypes of FOXP3 splice variants, including pre-mature FOXP3 and full length FOXP3 (FOXP3fl). We investigated the association between FOXP3 splice variant levels and the declines in estimated glomerular filtration rate (eGFR) of more than 5ml/min/1.73m2 within the first-year post-transplant using logistic regression.

Results

We observed lower FOXP3fl levels in recipients with declining eGFR (N = 132) than in recipients with stable eGFR (N = 201), (logarithmic value -4.13 [IQR -4.50 to -3.84] vs -4.00 [4.32 to -3.74], p=0.02). In ad hoc analysis pre-transplant FOXP3fl levels were similar in both groups. The association between FOXP3fl and declining eGFR was confirmed by multivariable analysis adjusted for potential confounding factors (Odds Ratio 0.51, 95% confidence interval 0.28 to 0.91: p=0.02). When stratifying FOXP3fl levels into quartiles, recipients with lower day1 FOXP3fl had the highest rate of declining eGFR (p=0.04).

Conclusion

Low FOXP3fl splice variant levels at the first postoperative day in kidney transplant recipients were associated with severe decline of eGFR, a well-known surrogate for hard endpoints.
Rare COVID-19 vaccine side effects got lost in the shuffle. Primary cutaneous lymphomas following COVID-19 vaccination: a systematic review
Authors: Olszewska Berenika , Zaryczańska Anna , Nowicki Roman J. , Sokołowska-Wojdyło Małgorzata
Published: April 2024

Introduction

COVID-19 vaccines are generally safe and effective; however, they are associated with various vaccine-induced cutaneous side effects. Several reported cases of primary cutaneous lymphomas (CLs) following the COVID-19 vaccination have raised concerns about a possible association. This systematic review aims to investigate and elucidate the potential link between CLs and SARS-CoV-2 vaccines.

Methods

We performed a systematic literature search on PubMed, EBSCO and Scopus from January 01, 2019, to March 01, 2023, and analyzed studies based on determined eligibility criteria. The systematic review was performed based on the PRISMA protocol.

Results

A total of 12 articles (encompassing 24 patients) were included in this analysis. The majority of CLs were indolent cutaneous T-cell lymphomas (CTCLs) (66,7%; 16/24), with Lymphomatoid papulosis (LyP) being the most common type (33,3%; 8/24). Most patients (79,2%; 19/24) developed lesions after receiving the COVID-19 mRNA-based vaccines, and predominantly after the first immunization dose (54,2%; 13/24). The presented CLs cases exhibited a tendency to exacerbate following subsequent COVID-19 vaccinations. Nevertheless, CLs were characterized by a favorable course, leading to remission in most cases.

Conclusion

The available literature suggests an association between the occurrence and exacerbation of CLs with immune stimulation following COVID-19 vaccination. We hypothesize that post-vaccine CLs result from an interplay between cytokines and disrupted signaling pathways triggered by vaccine components, concurrently playing a pivotal role in the pathomechanism of CLs. However, establishing a definitive causal relationship between these events is currently challenging, primarily due to the relatively low rate of reported post-vaccine CLs. Nonetheless, these cases should not be disregarded, and patients with a history of lymphoproliferative disorders require post-COVID-19 vaccination monitoring to control the disease’s course.

Systematic review registrationwww.researchregistry.com, identifier [1723].
Microbial signatures and enterotype clusters in fattening pigs: implications for nitrogen utilization efficiency
Authors: Sarpong Naomi , Seifert Jana , Bennewitz Jörn , Rodehutscord Markus , Camarinha-Silva Amélia
Published: April 2024

As global demand for pork continues to rise, strategies to enhance nitrogen utilization efficiency (NUE) in pig farming have become vital for environmental sustainability. This study explored the relationship between the fecal microbiota, their metabolites, and NUE in crossbreed fattening pigs with a defined family structure. Pigs were kept under standardized conditions and fed in a two-phase feeding regime. In each phase, one fecal sample was collected from each pig. DNA was extracted from a total of 892 fecal samples and subjected to target amplicon sequencing. The results indicated an influence of sire, sampling period (SP), and sex on the fecal microbiota. Streptococcus emerged as a potential biomarker in comparing high and low NUE pigs in SP 1, suggesting a genetic predisposition to NUE regarding the fecal microbiota. All fecal samples were grouped into two enterotype-like clusters named cluster LACTO and cluster CSST. Pigs’ affiliation with enterotype-like clusters altered over time and might be sex-dependent. The stable cluster CSST demonstrated the highest NUE despite containing pigs with lower performance characteristics such as average daily gain, dry matter intake, and daily nitrogen retention. This research contributes with valuable insights into the microbiome’s role in NUE, paving the way for future strategies to enhance sustainable pig production.
Ammonia-oxidizing archaea adapted better to the dark, alkaline oligotrophic karst cave than their bacterial counterparts
Authors: Li Qing , Cheng Xiaoyu , Liu Xiaoyan , Gao Pengfei , Wang Hongmei , Su Chuntian , Huang Qibo
Published: April 2024

Subsurface karst caves provide unique opportunities to study the deep biosphere, shedding light on microbial contribution to elemental cycling. Although ammonia oxidation driven by both ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) is well explored in soil and marine environments, our understanding in the subsurface biosphere still remained limited to date. To address this gap, weathered rock and sediment samples were collected from the Xincuntun Cave in Guilin City, an alkaline karst cave, and subjected to high-throughput sequencing and quantification of bacterial and archaeal amoA, along with determination of the potential nitrification rates (PNR). Results revealed that AOA dominated in ammonia oxidation, contributing 48–100% to the PNR, and AOA amoA gene copies outnumbered AOB by 2 to 6 orders. Nitrososphaera dominated in AOA communities, while Nitrosopira dominated AOB communities. AOA demonstrated significantly larger niche breadth than AOB. The development of AOA communities was influenced by deterministic processes (50.71%), while AOB communities were predominantly influenced by stochastic processes. TOC, NH4+, and Cl− played crucial roles in shaping the compositions of ammonia oxidizers at the OTU level. Cross-domain co-occurrence networks highlighted the dominance of AOA nodes in the networks and positive associations between AOA and AOB, especially in the inner zone, suggesting collaborative effort to thrive in extreme environments. Their high gene copies, dominance in the interaction with ammonia oxidizing bacteria, expansive niche breadth and substantial contribution to PNR collectively confirmed that AOA better adapted to alkaline, oligotrophic karst caves environments, and thus play a fundamental role in nitrogen cycling in subsurface biosphere.
Tapping the biosynthetic potential of marine Bacillus licheniformis LHG166, a prolific sulphated exopolysaccharide producer: structural insights, bio-prospecting its antioxidant, antifungal, antibacterial and anti-biofilm potency as a novel anti-infective lead
Authors: Alharbi Nada K. , Azeez Zahraa Falah , Alhussain Haitham Mohammed , Shahlol Aisha M. A. , Albureikan Mona Othman I. , Elsehrawy Mohamed Gamal , Aloraini Ghfren S. , El-Nablaway Mohammad , Khatrawi Elham Mohammed , Ghareeb Ahmed
Published: April 2024

The escalating global threat of antimicrobial resistance necessitates prospecting uncharted microbial biodiversity for novel therapeutic leads. This study mines the promising chemical richness of Bacillus licheniformis LHG166, a prolific exopolysaccharide (EPSR2-7.22 g/L). It comprised 5 different monosaccharides with 48.11% uronic acid, 17.40% sulfate groups, and 6.09% N-acetyl glucosamine residues. EPSR2 displayed potent antioxidant activity in DPPH and ABTS+, TAC and FRAP assays. Of all the fungi tested, the yeast Candida albicans displayed the highest susceptibility and antibiofilm inhibition. The fungi Aspergillus niger and Penicillium glabrum showed moderate EPSR2 susceptibility. In contrast, the fungi Mucor circinelloides and Trichoderma harzianum were resistant. Among G+ve tested bacteria, Enterococcus faecalis was the most susceptible, while Salmonella typhi was the most sensitive to G−ve pathogens. Encouragingly, EPSR2 predominantly demonstrated bactericidal effects against both bacterial classes based on MBC/MIC of either 1 or 2 superior Gentamicin. At 75% of MBC, EPSR2 displayed the highest anti-biofilm activity of 88.30% against B. subtilis, while for G−ve antibiofilm inhibition, At 75% of MBC, EPSR2 displayed the highest anti-biofilm activity of 96.63% against Escherichia coli, Even at the lowest dose of 25% MBC, EPSR2 reduced biofilm formation by 84.13% in E. coli, 61.46% in B. subtilis. The microbial metabolite EPSR2 from Bacillus licheniformis LHG166 shows promise as an eco-friendly natural antibiotic alternative for treating infections and oxidative stress.
Branched-chain amino acids and the risks of dementia, Alzheimer’s disease, and Parkinson’s disease
Authors: Fu Yidong , Wang Yue , Ren Huiming , Guo Xu , Han Liyuan
Published: April 2024

Background

We aimed to examine the association between blood levels of Branched-chain amino acids (BCAAs) - specifically isoleucine, leucine, and valine - and the susceptibility to three neurodegenerative disorders: dementia, Alzheimer’s disease (AD), and Parkinson’s disease (PD).

Methods

Based on data from the UK Biobank, a Cox proportional hazard regression model and a dose–response relationship were used to analyze the association between BCAAs and the risks of dementia, AD, and PD. We also generated a healthy lifestyle score and a polygenic risk score. Besides, we conducted a sensitivity analysis to ensure the robustness of our findings.

Results

After adjusting for multiple covariates, blood concentrations of isoleucine, leucine, and valine were significantly associated with a reduced risk of dementia and AD. This association remained robust even in sensitivity analyses. Similarly, higher levels of isoleucine and leucine in the blood were found to be associated with an increased risk of PD, but this positive correlation could potentially be explained by the presence of covariates. Further analysis using a dose–response approach revealed that a blood leucine concentration of 2.14 mmol/L was associated with the lowest risk of dementia.

Conclusion

BCAAs have the potential to serve as a biomarker for dementia and AD. However, the specific mechanism through which BCAAs are linked to the development of dementia, AD, and PD remains unclear and necessitates additional investigation.
A comprehensive review of advanced trends: from artificial synapses to neuromorphic systems with consideration of non-ideal effects
Authors: Kim Kyuree , Song Min Suk , Hwang Hwiho , Hwang Sungmin , Kim Hyungjin
Published: April 2024

A neuromorphic system is composed of hardware-based artificial neurons and synaptic devices, designed to improve the efficiency of neural computations inspired by energy-efficient and parallel operations of the biological nervous system. A synaptic device-based array can compute vector–matrix multiplication (VMM) with given input voltage signals, as a non-volatile memory device stores the weight information of the neural network in the form of conductance or capacitance. However, unlike software-based neural networks, the neuromorphic system unavoidably exhibits non-ideal characteristics that can have an adverse impact on overall system performance. In this study, the characteristics required for synaptic devices and their importance are discussed, depending on the targeted application. We categorize synaptic devices into two types: conductance-based and capacitance-based, and thoroughly explore the operations and characteristics of each device. The array structure according to the device structure and the VMM operation mechanism of each structure are analyzed, including recent advances in array-level implementation of synaptic devices. Furthermore, we reviewed studies to minimize the effect of hardware non-idealities, which degrades the performance of hardware neural networks. These studies introduce techniques in hardware and signal engineering, as well as software-hardware co-optimization, to address these non-idealities through compensation approaches.
Characterization of thyrotropin-releasing hormone producing neurons in sea urchin, from larva to juvenile
Authors: Cocurullo Maria , Paganos Periklis , Benvenuto Giovanna , Arnone Maria Ina
Published: April 2024

Most sea urchin species are indirect developers, going through a larval stage called pluteus. The pluteus possesses its own nervous system, consisting mainly of the apical organ neurons (controlling metamorphosis and settlement) and ciliary band neurons (controlling swimming behavior and food collection). Additional neurons are located in various areas of the gut. In recent years, the molecular complexity of this apparently “simple” nervous system has become apparent, with at least 12 neuronal populations identified through scRNA-sequencing in the species Strongylocentrotus purpuratus. Among these, there is a cluster of neurosecretory cells that produce a thyrotropin-releasing hormone-type neuropeptide (TRHergic) and that are also photosensory (expressing a Go-Opsin). However, much less is known about the organization of the nervous system in other sea urchin species. The aim of this work was to thoroughly characterize the localization of the TRHergic cells from early pluteus to juvenile stages in the Mediterranean sea urchin species Paracentrotus lividus combining immunostaining and whole mount in situ hybridization. We also compared the localization of TRHergic cells in early plutei of two other sea urchin species, Arbacia lixula and Heliocidaris tuberculata. This work provides new information on the anatomy and development of the nervous system in sea urchins. Moreover, by comparing the molecular signature of the TRHergic cells in P. lividus and S. purpuratus, we have obtained new insights how TRH-type neuropeptide signaling evolved in relatively closely related species.
A novel pathogenic SLC12A5 missense variant in epilepsy of infancy with migrating focal seizures causes impaired KCC2 chloride extrusion
Authors: Järvelä Viivi , Hamze Mira , Komulainen-Ebrahim Jonna , Rahikkala Elisa , Piispala Johanna , Kallio Mika , Kangas Salla M. , Nickl Tereza , Huttula Marko , Hinttala Reetta , Uusimaa Johanna , Medina Igor , Immonen Esa-Ville
Published: April 2024

The potassium-chloride co-transporter 2, KCC2, is a neuron-specific ion transporter that plays a multifunctional role in neuronal development. In mature neurons, KCC2 maintains a low enough intracellular chloride concentration essential for inhibitory neurotransmission. During recent years, pathogenic variants in the KCC2 encoding gene SLC12A5 affecting the functionality or expression of the transporter protein have been described in several patients with epilepsy of infancy with migrating focal seizures (EIMFS), a devastating early-onset developmental and epileptic encephalopathy. In this study, we identified a novel recessively inherited SLC12A5 c.692G>A, p. (R231H) variant in a patient diagnosed with severe and drug-resistant EIMFS and profound intellectual disability. The functionality of the variant was assessed in vitro by means of gramicidin-perforated patch-clamp experiments and ammonium flux assay, both of which indicated a significant reduction in chloride extrusion. Based on surface immunolabeling, the variant showed a reduction in membrane expression. These findings implicate pathogenicity of the SLC12A5 variant that leads to impaired inhibitory neurotransmission, increasing probability for hyperexcitability and epileptogenesis.
Patient-centered nutrition education improved the eating behavior of persons with uncontrolled type 2 diabetes mellitus in North Ethiopia: a quasi-experimental study
Authors: Gebreyesus Hagos Amare , Abreha Girmatsion Fisseha , Beshirie Sintayehu Degu , Abera Merhawit Atsbha , Weldegerima Abraha Hailu , Bezabih Afework Mulugeta , Lemma Tefera Belachew , Nigatu Tsinuel Girma
Published: April 2024

Background

Improving the clinical outcome of people with type 2 diabetes mellitus by modifying their eating behavior through nutrition education is an important element of diabetes self-management. Significant data from the literature supports this idea, however in the Ethiopian setting, there is a practice gap. Therefore, the purpose of this study was to assess how patient-centered nutrition education affected the eating behavior and clinical outcomes of people with uncontrolled type 2 diabetes mellitus.

Method

In this quasi-experimental trial, 178 people with uncontrolled type 2 diabetes were purposely assigned to the intervention (n = 89) or control (n = 89) arm. The intervention arm was given patient-centered nutrition education, whereas the control arm received the routine care. Eating behavior and clinical outcome indicators such as HbAc, lipid profile, anthropometric indices, and blood pressure were assessed in both groups at the start and completion of the intervention. All scale variables were tested for normality and log transformed when appropriate. The baseline characteristics of the intervention and control groups were compared using the t-test for continuous variables and the chi-square test for categorical variables. The effect of nutrition education was determined using a difference in differences (DID) approach. P < 0.05 was established as the criterion of significance.

Result

Food selection (DID = 15.84, P < 0.001), meal planning (DID = 31.11, P < 0.001), and calorie needs (DID = 37.65, P < 0.001) scores were statistically higher in the nutrition education arm. Furthermore, their overall eating behavior score (DID = 27.06, P < 0.001) was statistically greater than the controls. In terms of clinical outcomes, the overall picture reveals that the intervention did not outperform over the routine care. However, in comparison to the controls, the intervention arm showed clinically significant improvement in HbA1c (DID = −0.258, P = 0.485).

Conclusion

Patient-centered nutrition education has resulted in positive adjustments in the eating behavior of people with uncontrolled type 2 diabetes mellitus. Furthermore, it has shown a great potential for improving their glycemic control.
Lipid-based nanoparticles as drug delivery carriers for cancer therapy
Authors: Waheed Ibtesam , Ali Anwar , Tabassum Huma , Khatoon Narjis , Lai Wing-Fu , Zhou Xin
Published: April 2024

Cancer is a severe disease that results in death in all countries of the world. A nano-based drug delivery approach is the best alternative, directly targeting cancer tumor cells with improved drug cellular uptake. Different types of nanoparticle-based drug carriers are advanced for the treatment of cancer, and to increase the therapeutic effectiveness and safety of cancer therapy, many substances have been looked into as drug carriers. Lipid-based nanoparticles (LBNPs) have significantly attracted interest recently. These natural biomolecules that alternate to other polymers are frequently recycled in medicine due to their amphipathic properties. Lipid nanoparticles typically provide a variety of benefits, including biocompatibility and biodegradability. This review covers different classes of LBNPs, including their characterization and different synthesis technologies. This review discusses the most significant advancements in lipid nanoparticle technology and their use in medicine administration. Moreover, the review also emphasized the applications of lipid nanoparticles that are used in different cancer treatment types.
Correctly identifying the cells of origin is essential for tailoring treatment and understanding the emergence of cancer stem cells and late metastases
Authors: Waldum Helge , Slupphaug Geir
Published: April 2024

Malignancy manifests itself by deregulated growth and the ability to invade surrounding tissues or metastasize to other organs. These properties are due to genetic and/or epigenetic changes, most often mutations. Many aspects of carcinogenesis are known, but the cell of origin has been insufficiently focused on, which is unfortunate since the regulation of its growth is essential to understand the carcinogenic process and guide treatment. Similarly, the concept of cancer stem cells as cells having the ability to stop proliferation and rest in a state of dormancy and being resistant to cytotoxic drugs before “waking up” and become a highly malignant tumor recurrence, is not fully understood. Some tumors may recur after decades, a phenomenon probably also connected to cancer stem cells. The present review shows that many of these questions are related to the cell of origin as differentiated cells being long-term stimulated to proliferation.
Association of temperature management strategy with fever in critically ill children after out-of-hospital cardiac arrest
Authors: Kadden Micah , Zhang Anqing , Shoykhet Michael
Published: April 2024

Objective

To determine whether ICU temperature management strategy is associated with fever in children with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA).

Methods

We conducted a single-center retrospective cohort study at a quaternary Children's hospital between 1/1/2016–31/12/2020. Mechanically ventilated children (<18 y/o) admitted to Pediatric or Cardiac ICU (PICU/CICU) with ROSC after OHCA who survived at least 72 h were included. Primary exposure was initial PICU/CICU temperature management strategy of: (1) passive management; or (2) warming with an air-warming blanket; or (3) targeted temperature management with a heating/cooling (homeothermic) blanket. Primary outcome was fever (≥38°C) within 72 h of admission.

Results

Over the study period, 111 children with ROSC after OHCA were admitted to PICU/CICU, received mechanical ventilation and survived at least 72 h. Median age was 31 (IQR 6–135) months, 64% (71/111) were male, and 49% (54/111) were previously healthy. Fever within 72 h of admission occurred in 51% (57/111) of patients. The choice of initial temperature management strategy was associated with occurrence of fever (χ2 = 9.36, df = 2, p = 0.009). Fever occurred in 60% (43/72) of patients managed passively, 45% (13/29) of patients managed with the air-warming blanket and 10% (1/10) of patients managed with the homeothermic blanket. Compared to passive management, use of homeothermic, but not of air-warming, blanket reduced fever risk [homeothermic: Risk Ratio (RR) = 0.17, 95%CI 0.03–0.69; air-warming: RR = 0.75, 95%CI 0.46–1.12]. To prevent fever in one child using a homeothermic blanket, number needed to treat (NNT) = 2.

Conclusion

In critically ill children with ROSC after OHCA, ICU temperature management strategy is associated with fever. Use of a heating/cooling blanket with homeothermic feedback reduces fever incidence during post-arrest care.
Laser-induced damages to charge coupled devices with combined nanosecond/picosecond short-pulse lasers
Authors: Cao He , Xie Xiaofan , Chang Hao , Li Yunfei , Yue Jianfeng , Yu Yu , Wang Gong , Tang Ziqi , Li Lifang , Wang Yulei , Lu Zhiwei
Published: April 2024

The research on laser induced breakdown mechanism of charge coupled devices (CCDs) brings new insights into photoelectric countermeasures. So far combined laser irradiation has been proved to be a more effective measure to destroy CCD. Due to the limitation of short-pulse laser combination method, the mechanism of CCD damage caused by combined short-pulse laser remains unexplored. Here, the distribution of temperature and stress field during the interaction between a combined short-pulse laser and a CCD is analyzed. A nanosecond/picosecond combined short-pulse laser system based on Stimulated Brillouin Scattering (SBS) pulse compression technique is designed. The damage threshold (DT) and properties of CCD by combined laser irradiation are characterized. The results show that the complete DT of combined laser induced CCD breakdown is only 103 mJ/cm2, which is only 44% of that of picosecond laser. The main cause of combined short-pulse laser induced CCD breakdown is short circuit (SC) between silicon substrate and silicon electrode.
Erythroid anion transport, nitric oxide, and blood pressure
Authors: Hsu Kate
Published: April 2024

Glycophorin A and glycophorin B are structural membrane glycoproteins bound in the band 3 multiprotein complexes on human red blood cells (RBCs). Band 3 is an erythroid-specific anion exchanger (AE1). AE1-mediated HCO3− transport provides the substrate for the enzyme-catalyzed conversion HCO3−(aq) ⇌ CO2(g), which takes place inside the RBCs. Bicarbonate transport via AE1 supports intravascular acid–base homeostasis and respiratory excretion of CO2. In the past decade, we conducted several comparative physiology studies on Taiwanese people having the glycophorin variant GPMur RBC type (which accompanies greater AE1 expression). We found that increased anion transport across the erythrocyte membrane not only enhances gas exchange and lung functions but also elevates blood pressure (BP) and reduces nitric oxide (NO)-dependent vasodilation and exhaled NO fraction (FeNO) in healthy individuals with GP.Mur. Notably, in people carrying the GPMur blood type, the BP and NO-dependent, flow-mediated vasodilation (FMD) are both more strongly correlated with individual hemoglobin (Hb) levels. As blood NO and nitrite (NO2−) are predominantly scavenged by intraerythrocytic Hb, and NO2− primarily enters RBCs via AE1, could a more monoanion-permeable RBC membrane (i.e., GPMur/increased AE1) enhance NO2−/NO3− permeability and Hb scavenging of NO2− and NO to affect blood pressure? In this perspective, a working model is proposed for the potential role of AE1 in intravascular NO availability, blood pressure, and clinical relevance.
The two C. elegans class VI myosins, SPE-15/HUM-3 and HUM-8, share similar motor properties, but have distinct developmental and tissue expression patterns
Authors: Behbehani Ranya , Johnson Chloe , Holmes Alexander J. , Gratian Matthew J. , Mulvihill Daniel P. , Buss Folma
Published: April 2024

Myosins of class VI move toward the minus-end of actin filaments and play vital roles in cellular processes such as endocytosis, autophagy, protein secretion, and the regulation of actin filament dynamics. In contrast to the majority of metazoan organisms examined to date which contain a single MYO6 gene, C. elegans, possesses two MYO6 homologues, SPE-15/HUM-3 and HUM-8. Through a combination of in vitro biochemical/biophysical analysis and cellular assays, we confirmed that both SPE-15/HUM-3 and HUM-8 exhibit reverse directionality, velocities, and ATPase activity similar to human MYO6. Our characterization also revealed that unlike SPE-15/HUM-3, HUM-8 is expressed as two distinct splice isoforms, one with an additional unique 14 amino acid insert in the cargo-binding domain. While lipid and adaptor binding sites are conserved in SPE-15/HUM-3 and HUM-8, this conservation does not enable recruitment to endosomes in mammalian cells. Finally, we performed super-resolution confocal imaging on transgenic worms expressing either mNeonGreen SPE-15/HUM-3 or wrmScarlet HUM-8. Our results show a clear distinction in tissue distribution between SPE-15/HUM-3 and HUM-8. While SPE-15/HUM-3 exhibited specific expression in the gonads and neuronal tissue in the head, HUM-8 was exclusively localized in the intestinal epithelium. Overall, these findings align with the established tissue distributions and localizations of human MYO6.
An efficient in vitro organogenesis protocol for the endangered relic tree species Bretschneidera sinensis and genetic fidelity assessment using DNA markers
Authors: Yan Xuetong , Zheng Keyuan , Li Peng , Zhong Xin , Zhu Zongwei , Zhou Huijing , Zhu Mulan
Published: April 2024

Bretschneidera sinensis is a monotypic species of rare and tertiary relic trees mainly distributed in China. B. sinensis is a potentially valuable horticultural plant, which has significant ornamental and research value, and is a crucial tool for the study of phylogeography. The artificial cultivation of B. sinensis is of great scientific value and practical significance. In this study, we developed a direct organogenesis process of B. sinensis using mature zygotic embryos as initial materials. The highest sterile germination induction (54.5%) from the mature zygotic embryo was obtained in a Murashige and Skoog (MS) medium with 2.0 mg·L−1 6-benzylaminopurine (6-BA) and 0.2 mg·L−1 α-naphthaleneacetic acid (NAA). The highest percentage of shoot regeneration (90.37%) was attained using 1.0 mg·L−1 6-BA and 0.01 mg·L−1 NAA in the MS medium. The Woody Plant Medium (WPM) had the greatest adventitious shoot elongation rate of 93.33%. The most optimized rooting rate was 88.89% in a half-strength MS medium containing 2.0 mg·L−1 indole-3-butyric acid (IBA) and 1.0 mg·L−1 NAA. The genetic fidelity of in vitro regenerated plantlets was assessed using inter-simple sequence repeats and random amplified polymorphic DNA molecular markers, confirming the genetic uniformity and stability of regenerated B. sinensis plantlets. Our research presents an effective in vitro propagation system for B. sinensis, laying the groundwork for its germplasm conservation and large-scale production while maintaining high genetic integrity.
Genome-wide association study of plant color in Sorghum bicolor
Authors: Wang Lihua , Tu Wenmiao , Jin Peng , Liu Yanlong , Du Junli , Zheng Jiacheng , Wang Yi-Hong , Li Jieqin
Published: April 2024

Introduction

Sorghum plant color is the leaf sheath/leaf color and is associated with seed color, tannin and phenol content, head blight disease incidence, and phytoalexin production.

Results

In this study, we evaluated plant color of the sorghum mini core collection by scoring leaf sheath/leaf color at maturity as tan, red, or purple across three testing environments and performed genome-wide association mapping (GWAS) with 6,094,317 SNPs markers.

Results and Discussion

Eight loci, one each on chromosomes 1, 2, 4, and 6 and two on chromosomes 5 and 9, were mapped. All loci contained one to three candidate genes. In qPC5-1, Sobic.005G165632 and Sobic.005G165700 were located in the same linkage disequilibrium (LD) block. In qPC6, Sobic.006G149650 and Sobic.006G149700 were located in the different LD block. The single peak in qPC6 covered one gene, Sobic.006G149700, which was a senescence regulator. We found a loose correlation between the degree of linkage and tissue/organ expression of the underlying genes possibly related to the plant color phenotype. Allele analysis indicated that none of the linked SNPs can differentiate between red and purple accessions whereas all linked SNPs can differentiate tan from red/purple accessions. The candidate genes and SNP markers may facilitate the elucidation of plant color development as well as molecular plant breeding.
Genome-wide identification and expression analysis of the cryptochromes reveal the CsCRY1 role under low-light-stress in cucumber
Authors: Cao Haishun , Wang Rui , Zhao Junhong , Shi Liangliang , Huang Yuan , Wu Tingquan , Zhang Changyuan
Published: April 2024

Introduction

Low-light-stress is a common meteorological disaster that can result in slender seedlings. The photoreceptors play a crucial role in perceiving and regulating plants' tolerance to low-light-stress. However, the low-light-stress tolerance of cucumber has not been effectively evaluated, and the functions of these photoreceptor genes in cucumber, particularly under low-light-stress conditions, are not clear.

Methods

Herein, we evaluated the growth characteristics of cucumber seedlings under various LED light treatment. The low-light-stress tolerant cucumber CR and intolerant cucumber CR were used as plant materials for gene expression analysis, and then the function of CsCRY1 was analyzed.

Results

The results revealed that light treatment below 40 μmol m-2 s-1 can quickly and effectively induce low-light-stress response. Then, cucumber CR exhibited remarkable tolerance to low-light-stress was screened. Moreover, a total of 11 photoreceptor genes were identified and evaluated. Among them, the cryptochrome 1 (CRY1) had the highest expression level and was only induced in the low-light sensitive cucumber CS. The transcript CsaV3_3G047490.1 is predicted to encode a previously unknown CsCRY1 protein, which lacks 70 amino acids at its C-terminus due to alternative 5′ splice sites within the final intron of the CsCRY1 gene.

Discussion

CRY1 is a crucial photoreceptor that plays pivotal roles in regulating plants' tolerance to low-light stress. In this study, we discovered that alternative splicing of CsCRY1 generates multiple transcripts encoding distinct CsCRY1 protein variants, providing valuable insights for future exploration and utilization of CsCRY1 in cucumber.
How music-induced emotions affect sexual attraction: evolutionary implications
Authors: Marin Manuela M. , Gingras Bruno
Published: April 2024

More than a century ago, Darwin proposed a putative role for music in sexual attraction (i.e., sex appeal), a hypothesis that has recently gained traction in the field of music psychology. In his writings, Darwin particularly emphasized the charming aspects of music. Across a broad range of cultures, music has a profound impact on humans’ feelings, thoughts and behavior. Human mate choice is determined by the interplay of several factors. A number of studies have shown that music and musicality (i.e., the ability to produce and enjoy music) exert a positive influence on the evaluation of potential sexual partners. Here, we critically review the latest empirical literature on how and why music and musicality affect sexual attraction by considering the role of music-induced emotion and arousal in listeners as well as other socio-biological mechanisms. Following a short overview of current theories about the origins of musicality, we present studies that examine the impact of music and musicality on sexual attraction in different social settings. We differentiate between emotion-based influences related to the subjective experience of music as sound and effects associated with perceived musical ability or creativity in a potential partner. By integrating studies using various behavioral methods, we link current research strands that investigate how music influences sexual attraction and suggest promising avenues for future research.