Miracle-dz/UniFAR-FTUs huggingface dataset:
Mangiferin Alleviates Mitochondrial ROS in Nucleus Pulposus Cells and Protects against Intervertebral Disc Degeneration via Suppression of NF-κB Signaling Pathway

Intervertebral disc degeneration (IVDD), one of the most common clinical diseases worldwide, causes disc herniation and sciatica. Recent studies have identified the involvement of mitochondrial dysfunction, inflammatory responses, and extracellular matrix degradation in IVDD. Mangiferin is known to protect against various diseases by inhibiting oxidative stress, suppressing inflammation reaction, and relieving mitochondrial dysfunction. Whether mangiferin can alleviate IVDD remains to be elucidated. In the present study, human nucleus pulposus cells (HNPCs) and mouse intervertebral discs were cultured and stimulated with TNF-α, with or without treatment of mangiferin. Moreover, we established a rat needle puncture model and injected mangiferin into the intervertebral discs to verify its protective effect on IVDD. Furthermore, the activity of the NF-κB signaling pathway was tested in vitro. Our results indicated that mangiferin alleviated the inflammatory response and reversed the loss of major intervertebral disc components. Besides, mangiferin reduced reactive oxygen species production, ameliorated mitochondrial damage, and decreased the expression of apoptosis-related parameters in stimulation of TNF-α. In addition, mangiferin antagonized the activation of the NF-κB signaling pathway induced by TNF-α. Collectively, mangiferin antagonized mitochondrial ROS in NP cells and protected against IVDD by suppressing the activation of the NF-κB signaling pathway, which might provide a potential therapeutic instrument for IVDD.
Upregulating KTN1 promotes Hepatocellular Carcinoma progression

Background: Hepatocellular carcinoma (HCC) presents a common malignant tumor worldwide. Although kinectin 1 (KTN1) is the most frequently identified antigen in HCC tissues, the detailed roles of KTN1 in HCC remain unknown. This study seeks to clarify the expression status and clinical value of KTN1 in HCC and to explore the complicated biological functions of KTN1 and its underlying mechanisms. Methods: In-house reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of KTN1 in HCC tissues. External gene microarrays and RNA-sequencing datasets were downloaded to confirm the expression patterns of KTN1. The prognostic ability of KTN1 in HCC was assessed by a Kaplan-Meier curve and a hazard ratio forest plot. The CRISPR/Cas9 gene-editing system was used to knock out KTN1 in Huh7 cells, which was verified by PCR-Sanger sequencing and western blotting. Assays of cell migration, invasion, viability, cell cycle, and apoptosis were conducted to explore the biological functions. RNA sequencing was performed to quantitatively analyze the functional deregulation in KTN1-knockout cells compared to Huh7-wild-type cells. Upregulated genes that co-expressed with KTN1 were identified from HCC tissues and were functionally annotated. Results: KTN1 expression was increased in HCC tissues (standardized mean difference [SMD] = 0.20 [0.04, 0.37]). High KTN1 expression was significantly correlated with poorer prognosis of HCC patients, and KTN1 may be an independent risk factor for HCC (pooled HRs = 1.31 [1.05, 1.64]). After KTN1-knockout, the viability, migration, and invasion ability of HCC cells were inhibited. The proportion of HCC cells in the G0-G1 phases increased after KTN1 knockout, which also elevated the apoptosis rates in HCC cells. Several cascades, including innate immune response, chemical carcinogenesis, and positive regulation of transcription by RNA polymerase II, were dramatically changed after KTN1 knockout. KTN1 primarily participated in the cell cycle, DNA replication, and microRNAs in cancer pathways in HCC tissues. Conclusion: Upregulation of KTN1 served as a promising prognosticator in HCC patients. KTN1 promotes the occurrence and deterioration of HCC by mediating cell survival, migration, invasion, cell cycle activation, and apoptotic inhibition. KTN1 may be a therapeutic target in HCC patients.
Restricting Sales of Menthol Tobacco Products: Lessons Learned from Policy Passage and Implementation in Minneapolis, St. Paul, and Duluth, Minnesota

Purpose: Commercial tobacco products have historically been target marketed to African American, Latinx, Asian American Pacific Islander, Indigenous, and Lesbian, Gay, Bisexual, Transgender, Queer (LGBTQ) communities, as well as to youth. Menthol cigarettes increase smoking initiation and decrease smoking cessation, particularly among African Americans who smoke menthol cigarettes at higher rates than their white peers. Due to disproportionate tobacco-related health consequences for members of these communities, effective tobacco control policies that restrict availability of menthol products by focusing on retail sales are an important element of addressing health disparities, and require policy efforts informed by leadership and the voice of communities most impacted. This study examines the organizing efforts of three successful policy initiatives in 2017–2018 in Minneapolis, St. Paul, and Duluth, Minnesota, and identifies facilitators and barriers of these campaigns. Methods: We conducted 50 key informant interviews with city council/staff, advocates, and community members and analyzed them for emerging themes. The analysis employed a process-oriented qualitative matrix process to identify emerging themes and divergent perspectives. Results: Following policy implementation, outlets selling commercial menthol tobacco products substantially decreased. Facilitators included strong city council support, leadership from impacted communities, community awareness-building campaigns, and understanding tobacco industry counter-tactics. Challenges included the need to counter tobacco industry misinformation and retailer attempts to circumvent the intent of restrictions. Conclusion: Well-planned advocacy campaigns led by community members most impacted by commercial tobacco can overcome opposition and challenges to restrict sales of menthol tobacco products and successfully reduce availability of these products in their communities.
Lifestyle and Work-Related Factors Associated with Work Ability and Work Participation for People with Obesity: A Prospective Observational Study After Vocational Rehabilitation

Purpose We aimed to investigate which changes in the explanatory factors that were associated with positive change in the work ability score (WAS) and degree of work participation (DWP) for participants in a new 1-year vocational rehabilitation (VR) program for people on or at risk of sick leave due to obesity or obesity-related problems. Patients and Methods This prospective observational study included 95 participants with a body mass index (BMI) above 30 kg/m2. The 1-year multidisciplinary VR program with an integrated work and lifestyle intervention included 4 weeks of inpatient stay followed-up by five meetings. Differences between baseline and 12-month follow-up data were analyzed for the change in explanatory variables WAS, DWP, health-related quality of life (HRQoL), BMI, and return-to-work self-efficacy (RTWSE). The primary outcome was measured by multiple linear regression for predicting WAS and DWP. Results We found significant changes in WAS (1.51, 95% CI: 0.83 to 2.20, p<0.001), DWP (18.69, 95% CI: 8.35 to 29.02, p<0.001), HRQoL (2.57, 95% CI: 1.35 to 3.79, p<0.001), BMI (−2.33, 95% CI: −3.10 to −1.56, p<0.001), and in RTWSE (15.89, 95% CI: 4.07 to 27.71, p = 0.009). Regression analysis yielded a strong association between WAS at 12-month follow-up with an increase in HRQoL (β=0.27, 95% CI: 0.16 to 0.38, p<0.001) and WAS baseline (β=0.49, 95% CI: 0.28 to 0.71, p<0.001). Further, regression analysis demonstrated a strong association between DWP at 12-month follow-up with return-to-work expectancy (RTWEXP) (β=−10.62, 95% CI: −15.25 to −6.03, p<0.001). Conclusion The results indicate positive changes in WAS, DWP, HRQoL, BMI, and RTWSE from baseline to 12-month follow-up. For people with BMI above 30 kg/m2, changes in HRQoL are important for an increase in WAS, and a high RTWEXP is essential to achieve work participation. Future studies examining VR programs with lifestyle interventions for people with obesity are recommended.
Dependence of phase transition uniformity on crystal sizes characterized using birefringence

Solid–solid phase transitions (SSPTs) have been widely observed in crystals of organic or inorganic small-molecules. Although SSPTs in macromolecular crystals have been reported, the majority involve local atomic changes, such as those induced by changes in hydration. SSPTs driven by large conformational changes, however, can be more difficult to characterize since they often significantly disrupt lattice packing interactions. Such drastic changes make the cooperativity of molecular motion at the atomic level less easily achieved and more dependent on intrinsic properties of the crystal that define lattice order. Here, we investigate the effect of crystal size on the uniformity of SSPT in thin plate-like crystals of the adenine riboswitch aptamer RNA (riboA) by monitoring changes in crystal birefringence upon the diffusion of adenine ligand. The birefringence intensity is directly related to molecular order and the concurrent changes to polarizability of molecules that results from structural changes throughout the phase transition. The riboA crystals were loosely grouped into three categories (small, medium, and large) based on the surface area of the crystal plates. The time width of transition increased as a function of crystal size, ranging from ∼13 s for small crystals to ∼40 s for the largest crystal. Whereas the transitions in small crystals (<10 μm2) were mostly uniform throughout, the medium and large crystals exhibited large variations in the time and width of the transition peak depending on the region of the crystal being analyzed. Our study provides insight into the spatiotemporal behavior of phase transitions in crystals of biological molecules and is of general interest to time-resolved crystallographic studies, where the kinetics of conformational changes may be governed by the kinetics of an associated SSPT.
Predicting age from hearing test results with machine learning reveals the genetic and environmental factors underlying accelerated auditory aging

With the aging of the world population, age-related hearing loss (presbycusis) and other hearing disorders such as tinnitus become more prevalent, leading to reduced quality of life and social isolation. Unveiling the genetic and environmental factors leading to age-related auditory disorders could suggest lifestyle and therapeutic interventions to slow auditory aging. In the following, we built the first machine learning-based hearing age predictor by training models to predict chronological age from hearing test results (root mean squared error=7.10+/-0.07 years; R-Squared=31.4+/-0.8%). We defined hearing age as the prediction outputted by the model on unseen samples, and accelerated auditory aging as the difference between a participant's hearing age and age. We then performed a genome wide association study [GWAS] and found that accelerated hearing aging is 14.1+/-0.4% GWAS-heritable. Specifically, accelerated auditory aging is associated with 662 single nucleotide polymorphisms in 243 genes (e.g OR2B4P, involved in smell perception). Similarly, it is associated with biomarkers (e.g cognitive tests), clinical phenotypes (e.g chest pain), diseases (e.g depression), environmental (e.g smoking, sleep) and socioeconomic (e.g income, education, social support) variables. The hearing age predictor could be used to evaluate the efficiency of emerging rejuvenation therapies on hearing.
Patrolling the boundaries of social domains: Neural activations to violations of expectations for romantic and work relationships

ABSTRACT According to the social domains hypothesis, we reduce the information-processing demands of complex social cues by classifying them into a limited number of domains, each with distinct sets of expectations. This requires rapid identification of violations of the boundaries between social domains. We hypothesized that these violations are likely to be associated with neural activation of the salience system. Using fMRI we compared responses of 20 adults to expected and unexpected everyday social scenarios in personal and work interactions. The vignettes exemplified different kinds of scenarios presented in the work setting, i.e., task-focused scenarios which are expected at work and scenarios with a personal focus, which are unexpected at work. The key contrast between task and personal focussed scenarios presented in the work setting was associated with fronto-insular activation. Perceived inappropriateness of the unexpected scenarios, and shorter response time to judgment of inappropriateness were also associated with fronto-insular activation, after controlling for unpleasantness. This study indicates specific neural responses to violations of expectations in different social situations. Our findings suggest that the fronto-insular region is implicated in rapid detection of behaviors that cross the boundaries of social domains, which are hypothesized to be necessary for efficient social information processing.
Bumblebee (Hymenoptera: Apidae) Visitation Frequency Drives Seed Yields and Interacts with Site-Level Species Richness to Drive Pollination Services in Sunflower

Abstract Understanding whether pollinator behaviors and species richness drive crop yields is a key area of investigation in pollination ecology. Using sunflower as a study species we describe variation in mean floral visitation times among bee taxa and test how interactions between bee richness and the proportion of bumblebees in localized communities impact seed yield. Seven bee genera commonly visited sunflower including Agapostemon, Bombus, Halictus, Lasioglossum, Megachile, Melissodes, and Svastra. Mean visitation times to sunflower varied across genera and Bombus and Halictus spp. spent the most time foraging on inflorescences, but the number of visits by Bombus spp. was the only parameter associated with increased yields. Experimental pollination deficit reduced seed development and yields, and these effects were stronger in stands of wild-type sunflower in the field compared to a confection variety grown in the greenhouse. Relationships between bee richness and pollination services differed for potted and wild sunflower: when bees had short-term access to potted sunflower, bee richness and relative Bombus abundances were not associated with pollination quotients. When bees had long-term access to wild sunflower, relative Bombus abundances predicted pollination services but were modified by site-level bee richness: as richness increased, the effects of Bombus abundance decreased. Our studies demonstrate that bee species richness is not always a clear predictor of pollination services; instead, our results underscore the importance of specific taxa when species richness is low (here, bumblebees), and show that the effects of bee functional groups important for pollination may be modified by changes in site-level species richness.
Optimized Extraction of Ginsenosides from Ginseng Root (Panax ginseng C.A. Meyer) by Pulsed Electric Field Combined with Commercial Enzyme

Ginsenosides are the major active components in ginseng, which has been widely used for treatment diseases. In this study, the effects of pulsed electric fields (PEF) combined with commercial enzyme (CPEF) on the extraction of total saponin from ginseng root were investigated. The commercial β-glucosidase was more efficient for extracting total saponin under PEF treatment. Response surface methodology was carried out to optimize the yield of total saponin under CPEF treatment. The experimental data were fitted to a second-order polynomial equation. Optimal treatment conditions were as follows: electric field intensity 15 kV/cm, pulse number 10 and enzyme concentration 2% (w/w). Under these conditions, the validated experimental yield of total saponin was 38.15 mg/g, matching well with the predicted value. The extraction speed of CPEF treatment is much faster, and the yield of total saponin is higher compared with traditional methods. Practical Applications Panax ginseng C.A. Meyer (ginseng) is a well-known traditional medicinal plant. Ginsenosides are the most important secondary metabolites in ginseng and have various pharmacological activities. In the present study, pulsed electric field combined with commercial enzyme was applied to the extraction of total saponin from ginseng root. The results indicated that CPEF treatment can be an effective method to extract total saponin with nonthermal performance, high efficiency and lower energy consumption.
Using social marketing to persuade Iranians to donate blood

Abstract This study examined effects of a social marketing intervention to encourage people to donate blood in a southwest city of Iran. To design the intervention, the constructs of theory of planned behavior in 170 consistent blood donors were measured. Persuasive messages were developed, and some printed materials were prepared to transfer the message to the target segment. The trend of the percentage of consistent blood donors was measured during the first four months after the intervention. The percentage of consistent blood donors was increased significantly. The findings showed the effectiveness of the social marketing interventions for blood donation.
Ddx20, DEAD box helicase 20, is essential for the differentiation of oligodendrocyte and maintenance of myelin gene expression

Oligodendrocytes form myelin sheaths that surround axons, contributing to saltatory conduction and proper central nervous system (CNS) function. Oligodendrocyte progenitor cells (OPCs) are generated during the embryonic stage and differentiate into myelinating oligodendrocytes postnatally. Ddx20 is a multifunctional, DEAD‐box helicase involved in multiple cellular processes, including transcription, splicing, microRNA biogenesis, and translation. Although defects in each of these processes result in abnormal oligodendrocyte differentiation and myelination, the involvement of Ddx20 in oligodendrocyte terminal differentiation remains unknown. To address this question, we used Mbp‐Cre mice to generate Ddx20 conditional knockout (cKO) mice to allow for the deletion of Ddx20 from mature oligodendrocytes. Mbp‐Cre;Ddx20 cKO mice demonstrated small body sizes, behavioral abnormalities, muscle weakness, and short lifespans, with mortality by the age of 2 months old. Histological analyses demonstrated significant reductions in the number of mature oligodendrocytes and drastic reductions in the expression levels of myelin‐associated mRNAs, such as Mbp and Plp at postnatal day 42. The number of OPCs did not change. A thin myelin layer was observed for large‐diameter axons in Ddx20 cKO mice, based on electron microscopic analysis. A bromodeoxyuridine (BrdU) labeling experiment demonstrated that terminal differentiation was perturbed from ages 2 weeks to 7 weeks in the CNS of Mbp‐Cre;Ddx20 cKO mice. The activation of mitogen‐activated protein (MAP) kinase, which promotes myelination, was downregulated in the Ddx20 cKO mice based on immunohistochemical detection. These results indicate that Ddx20 is an essential factor for terminal differentiation of oligodendrocytes and maintenance of myelin gene expression.
Drug‐like sphingolipid SH‐BC‐893 opposes ceramide‐induced mitochondrial fission and corrects diet‐induced obesity

Ceramide‐induced mitochondrial fission drives high‐fat diet (HFD)‐induced obesity. However, molecules targeting mitochondrial dynamics have shown limited benefits in murine obesity models. Here, we reveal that these compounds are either unable to block ceramide‐induced mitochondrial fission or require extended incubation periods to be effective. In contrast, targeting endolysosomal trafficking events important for mitochondrial fission rapidly and robustly prevented ceramide‐induced disruptions in mitochondrial form and function. By simultaneously inhibiting ARF6‐ and PIKfyve‐dependent trafficking events, the synthetic sphingolipid SH‐BC‐893 blocked palmitate‐ and ceramide‐induced mitochondrial fission, preserved mitochondrial function, and prevented ER stress in vitro. Similar benefits were observed in the tissues of HFD‐fed mice. Within 4 h of oral administration, SH‐BC‐893 normalized mitochondrial morphology in the livers and brains of HFD‐fed mice, improved mitochondrial function in white adipose tissue, and corrected aberrant plasma leptin and adiponectin levels. As an interventional agent, SH‐BC‐893 restored normal body weight, glucose disposal, and hepatic lipid levels in mice consuming a HFD. In sum, the sphingolipid analog SH‐BC‐893 robustly and acutely blocks ceramide‐induced mitochondrial dysfunction, correcting diet‐induced obesity and its metabolic sequelae.
Central Nervous System-Infecting Pathogens Escherichia coli and Cryptococcus neoformans Exploit the Host Pdlim2 for Intracellular Traversal and Exocytosis in the Blood-Brain Barrier

Microbial penetration of the blood-brain barrier, a prerequisite for the development of central nervous system (CNS) infection, involves microbial invasion, intracellular traversal, and exocytosis. Microbial invasion of the blood-brain barrier has been investigated, but the molecular basis for microbial traversal and exit from the blood-brain barrier remains unknown. ABSTRACT Microbial penetration of the blood-brain barrier, a prerequisite for the development of central nervous system (CNS) infection, involves microbial invasion, intracellular traversal, and exocytosis. Microbial invasion of the blood-brain barrier has been investigated, but the molecular basis for microbial traversal and exit from the blood-brain barrier remains unknown. We performed transcriptome analysis of human brain microvascular endothelial cells (HBMEC) infected with Escherichia coli and Cryptococcus neoformans, representative bacterial and fungal pathogens common in CNS infections. Among the targets upregulated in response to E. coli and C. neoformans infection, PDLIM2 was knocked down by small hairpin RNA (shRNA) in HBMEC for further investigation. We demonstrated that Pdlim2 specifically regulated microbial traversal and exit from HBMEC by assessing microbial invasion, transcytosis, intracellular multiplication, and egression. Additionally, the defective exocytosis of internalized E. coli cells from the PDLIM2 shRNA knockdown cells was restored by treatment with a calcium ionophore (ionomycin). Moreover, we performed proximity-dependent biotin labeling with the biotin ligase BioID2 and identified 210 potential Pdlim2 interactors. Among the nine Pdlim2 interactors enriched in response to both E. coli and C. neoformans infection, we selected MPRIP and showed that HBMEC with knockdown of MPRIP mimicked the phenotype of PDLIM2 knockdown cells. These results suggest that the CNS-infecting microbes hijack Pdlim2 and Mprip for intracellular traversal and exocytosis in the blood-brain barrier.