Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxidative stress in Physella acuta: An integrative response of exposure to water from two rivers of Atlantic Mexican slope

Freshwater pollution is a complex mixture of xenobiotics due to the wastewater and the various chemicals routinely applied to agricultural lands that are discharged into water bodies. Xenobiotics can exert damage to the aquatic biota threatening the biodiversity of aquatic ecosystems. The oxidative damage and antioxidant responses have been widely investigated in freshwater organisms, mainly in fish and some invertebrates but in freshwater snails are scarce. This study aimed to assess the oxidative stress exerted by potential toxicity of water from two rivers of the Mexican Atlantic Slope (Tecolutla and Tuxpan rivers) in a freshwater mollusk Physella acuta. Lipid peroxidation level and a battery of antioxidant enzymes (Superoxide dismutase, Catalase and Glutathione peroxidase) were measured in P. acuta. The results are contextualized from an ecological point of view, associating the bioassay results with water quality characteristics. Water samples were obtained from three study sites for each river (in two seasons: Northern wind and dry). Twelve water quality variables were analyzed, and an additional water sample was used to perform a static bioassay for 96 h with snails grown in laboratory. After the exposure, we assessed lipid peroxidation level and the antioxidant responses of P. acuta exposed to water of rivers, and the Integrated Biomarker Response was computed. The highest lipid peroxidation level occurred in organisms exposed to water during the Northern wind season in both rivers. During this season, in the Tecolutla river, the superoxide dismutase activity was able to counteract the lipid peroxidation process, representing an adaptive response. In contrast, in the Tuxpan river, the superoxide dismutase was unable to counteract that process, stimulating CAT and GPx activities. The Integrated Biomarker Response showed that the Tecolutla river had higher values in the upper reaches than the Tuxpan river, showing a decreasing downstream gradient in both seasons. In the Tuxpan river, during the Dry season, the IBR score showed an increasing downstream gradient. During the Northern wind season, the IBR was higher in the upper reaches of both rivers, possibly due to the increased materials transported by runoff from the catchment, which includes a complex mixture of xenobiotics that affects the health of the sentinel species and aquatic biota in general. Based on our results, Physella acuta is proposed as sentinel species.
Causal associations between dietary antioxidant vitamin intake and lung cancer: A Mendelian randomization study

Background Oxidative stress is currently considered to be closely related to the occurrence of respiratory tumors, especially lung cancer. Many observational studies have shown that increased antioxidant intake can reduce the risk of lung cancer, but the results are still controversial. Therefore, we performed a two-sample Mendelian randomized (MR) analysis to clarify the causal relationship between antioxidant vitamins and lung cancer. Methods To assess the causal effect of dietary antioxidant vitamin intake on lung cancer, we conducted a two-sample MR analysis and we extracted single-nucleotide polymorphisms (SNPs) that are associated with antioxidants from genome-wide association studies (GWASs) of the UK biobank. We gathered summary data for lung cancer from the International Lung Cancer Consortium (ILCCO), including 11,348 cases and 15,861 controls, and applied the inverse-variance weighted (IVW) method as the primary MR analysis, and performed a sensitivity analysis to verify the results. Results The results showed that higher dietary retinol intake was causally associated with lung cancer overall [odds ratio (OR) = 1.844, 95% CI, 1.359–2.502, p = 0.00009], squamous cell lung cancer (OR = 2.162, 95% CI, 1.117–4.183, p = 0.022), and lung adenocarcinoma (OR = 1.706, 95% CI, 1.084–2.685, p = 0.021). Additionally, carotene was positively correlated with lung adenocarcinoma (OR = 1.510, 95% CI, 1.002–2.276, p = 0.049). However, there was a non-significant relationship between the intake of other dietary antioxidants (vitamin C and vitamin E) and lung cancer. Conclusion Our research showed that dietary retinol intake has an adverse impact on lung cancer, and carotene might increase the risk of adenocarcinoma. This highlights the importance of revealing the underlying mechanisms of dietary antioxidant vitamins in lung cancer and delivers an important health message that dietary antioxidant vitamin intake may not be necessary for the prevention of lung cancer. It also provides a basis for future research.
Intestinal anti-inflammatory and visceral analgesic effects of a Serpylli herba extract in an experimental model of irritable bowel syndrome in rats

Ethnopharmacological relevance: Serpylli herba extract (SHE), composed of the aerial parts of wild thyme (Thymus serpyllum L.) (Lamiaceae family), is traditionally used in Europe and North Africa to treat diarrhea, gastric ulcers, intestinal parasites and upper respiratory tract infections. Recently, SHE has generated a great interest for irritable bowel syndrome (IBS) management, probably due to its intestinal anti-inflammatory properties shown in experimental colitis and the fact that its active components could preserve the intestinal barrier integrity, which is altered in patients with IBS. Aim of study: We aimed to test the effects of a SHE in a rat experimental model resembling human IBS. Materials and methods: IBS was provoked by deoxycholic acid (DCA). Rats were then treated with SHE (100 mg/kg) or gabapentin (70 mg/kg) and different inflammatory and gut barrier integrity markers were evaluated. Moreover, several gut hypersensitivity and hyperalgesia determinations were performed. Results: SHE improved referred pain and visceral hypersensitivity. Additionally, SHE enhanced immune status by downregulating of the expression of the pro-inflammatory mediators Il-1β, Il-6, Ifn-γ, Tlr-4, and the inducible enzyme Cox-2, thus inducing visceral analgesia, and promoting the restore of the gut barrier function by upregulating the mucins Muc-2 and Muc-3. These anti-inflammatory effects could be related to its action on mast cells since it significantly inhibited the β-Hexosaminidase production in RBL-2H3 cells. Lastly, SHE also seems to modulate the serotonin pathway by restoring the altered expression of the 5-HT receptors Htr-3 and Htr-4. Conclusion: SHE could be considered a potential new treatment for IBS, since it ameliorates hypersensitivity, visceral hyperalgesia, and inflammation. These beneficial effects may be due to the inhibition of mast cells degranulation and serotonin pathway.
Does the Mediterranean diet reduce the odds of diabetic nephropathy in women? A case–control study

Background In recent decades, the prevalence of chronic diseases such as diabetes is increasing. One of the major complications of diabetes is diabetic nephropathy (DN), so it is important to find a way that can delay or control the onset of DN. Therefore, in this study, we investigated the relationship between the Mediterranean diet (MED) and the odds of DN. Methods This case–control study was performed among 210 women (30–65 years) who were referred to the Kowsar Diabetes Clinic in Semnan, Iran. Biochemical variables and anthropometric measurements were assessed. The food frequency questionnaire (FFQ) was used to calculate dietary intakes. Data from dietary intakes based on the FFQ were used to evaluate the MED score. Logistic regression was used to examine the associations. Results Our results showed that in the crude model with higher adherence to the MED (OR: 0.272; 95% CI: 0.154, 0.481; P = 0.001), the odds of DN has reduced by 73%, and in model 1, after controlling for potential confounders, with higher adherence to the MED (OR: 0.239; 95% CI: 0.128, 0.447; P = 0.001), the odds of DN has reduced by 76% compared to low adherence. Also, in model 1, significant associations were observed between high consumption of grains (OR: 0.360; 95% CI: 0.191, 0.676; P = 0.001), legumes (OR: 0.156; 95% CI: 0.083, 0.292; P = 0.001), vegetables (OR: 0.273; 95% CI: 0.149, 0.501; P = 0.001), fruits (OR: 0.179; 95% CI: 0.093, 0.347; P = 0.001), fish (OR: 0.459; 95% CI: 0.254, 0.827; P = 0.01), and reduced odds of DN (P < 0.05). Conclusion We observed that with higher adherence to the MED, the odds of DN had reduced through mechanisms. However, additional studies are needed to confirm these findings.
Lyman-alpha emission from the Lyman-alpha forest. [in high red shift quasar spectra due to molecular clouds]

It is suggested that high-dispersion long-slit spectra or very narrow-band etalon images of 'blank' sky could reveal patches of Ly-alpha line emission from the population of clouds whose absorption produces the 'Ly-alpha forest' in QSO spectra. A nonobservation can put limits on the ionizing background at high redshift which are better than those obtainable by direct measurements of background light.
Autism: A model of neurodevelopmental diversity informed by genomics

Definitions of autism are constantly in flux and the validity and utility of diagnostic criteria remain hotly debated. The boundaries of autism are unclear and there is considerable heterogeneity within autistic individuals. Autistic individuals experience a range of co-occurring conditions notably including other childhood onset neurodevelopmental conditions such as intellectual disability, epilepsy and ADHD, but also other neuropsychiatric conditions. Recently, the neurodiversity movement has challenged the conception of autism as a medical syndrome defined by functional deficits. Whereas others have argued that autistic individuals with the highest support needs, including those with intellectual disability and limited functional communication, are better represented by a medical model. Genomic research indicates that, rather than being a circumscribed biological entity, autism can be understood in relation to two continua. On the one hand, it can be conceived as lying on a continuum of population variation in social and adaptive functioning traits, reflecting in large part the combination of multiple alleles of small effect. On the other, it can be viewed as lying on a broader neurodevelopmental continuum whereby rare genetic mutations and environmental risk factors impact the developing brain, resulting in a diverse spectrum of outcomes including childhood-onset neurodevelopmental conditions as well as adult-onset psychiatric conditions such as schizophrenia. This model helps us understand heterogeneity within autism and to reconcile the view that autism is a part of natural variability, as advocated by the neurodiversity movement, with the presence of co-occurring disabilities and impairments of function in some autistic individuals.
POLD2 is activated by E2F1 to promote triple-negative breast cancer proliferation

Triple-negative breast cancer (TNBC) is a highly malignant breast cancer subtype with a poor prognosis. Improved insight into the molecular biology basis of TNBC progression is urgently needed. Herein, we reported that POLD2 was highly expressed in TNBC and patients with high POLD2 expression in their tumors had poor clinical outcomes. In functional studies, knockdown of POLD2 inhibited the proliferation of TNBC. Mechanistically, we revealed that transcription factor E2F1 directly bound to the promoter of POLD2 and regulated its expression in TNBC cells, which in turn contributed to the proliferation of TNBC. Additionally, rescue experiments validated that E2F1-mediated cell proliferation in TNBC was dependent on POLD2. Taken together, our results elucidated a novel mechanism of the E2F1-POLD2 axis in TNBC proliferation, and POLD2 may be a potential therapeutic target for TNBC treatment.
Eight gene mutation-based polygenic hazard score as a potential predictor for immune checkpoint inhibitor therapy outcome in metastatic melanoma

Background: Immune checkpoint inhibitor (ICI) therapies have revolutionized the treatment of metastatic cutaneous melanoma, but have only benefitted a subset of them. Gene mutations were reported to impact the ICI therapy outcomes in metastatic melanoma but have not been fully investigated. Hence, we systematically analyzed the impact of cancer-related gene mutations on the clinical outcome in metastatic melanoma patients who underwent ICI therapies. Methods: Publicly available discovery and validation cohorts (312 patients and 110 patients respectively, all the patients received ICI therapies) were included in this study. Cox proportional hazards regression analysis was used to assess the association of 468 cancer-related gene mutations with overall survival (OS) in the discovery cohort, and the polygenic hazard score (PHS) was constructed subsequently, and validated in the validation cohort. The Tumor Immune Estimation Resource (TIMER) online tools, which are based on The Cancer Genome Atlas database, were used to analyze the impact of gene mutations on tumor-infiltrated immune cells in melanoma samples. Results: We found eight gene mutations that were significantly associated with the overall survival (BAP1, CARD11, IGF1R, KMT2D, PTPRD, PTPRT, ROS1, and TERT, p < 0.05, mutation frequency >0.05). The PHS, which was based on these genes, was found to effectively discriminate the subset which benefited most from ICI therapies (HR = 1·54, 95%CI, 1.25–1.95; p < 0.001). After adjusting with age, sex, ICI regimes, and tumor mutation burden (TMB), we found that PHS was an independent predictor for the outcome of ICI therapies (adjusted HR = 1.84, 95%CI, 1.22–2.79; p = 0.004). The PHS was validated in the validation cohort (log-Rank p = 0.038). Further research found that CARD11 and PTPRD mutations were significantly associated with more tumor-infiltrated immune cells in melanoma samples. Conclusion: For the first time, we have shown that PHS can independently and effectively predict the ICI therapy outcome in metastatic melanoma, which once validated by larger research, may help the decision-making process in melanoma.
In vitro activity of anti-rheumatic drugs on release of pro-inflammatory cytokines from oral cells in interaction with microorganisms

Periodontitis patients suffering concomitantly from rheumatoid arthritis (RA) often present with less inflamed periodontal tissues due to the ongoing anti-rheumatic therapy. This in vitro study was aimed to analyze whether anti-inflammatory drugs used in the therapy of RA can modulate the release of IL-8 and IL-1β by professional and non-professional immune cells stimulated with microorganisms. Periodontal ligament (PDL) fibroblasts, monocytic MONO-MAC-6-cells, and gingival keratinocytes were exposed to ibuprofen, prednisolone, and methotrexate with and without lysates of Fusobacterium nucleatum or Candida albicans. Supernatants were obtained and the levels of interleukin(IL)-8 and IL-1β (only MONO-MAC-6) were quantified. The addition of F. nucleatum lysate resulted in the strongest release of proinflammatory cytokines by PDL fibroblast and MONO-MAC-6 cells, while the modification by the tested anti-rheumatic drugs was only minor. After stimulation of the MONO-MAC-cells with F. nucleatum, prednisolone increased the release of IL-8, whereas methotrexate decreased the level. Anti-inflammatory drugs increased the adherence of C. albicans to epithelial cells. In patients with RA, the reduction of the microbial load in subgingival biofilm (biofilm removal) is of major importance; however, the intake of inflammatory drugs may interfere with the inflammatory response.
Transcutaneous auricular vagus nerve immediate stimulation treatment for treatment-resistant depression: A functional magnetic resonance imaging study

Objective Transcutaneous auricular vagus nerve stimulation (taVNS) is effective for treatment-resistant depression (TRD). In the current study, we observed the immediate modulating brain effect of taVNS in patients with TRD using rest-state functional magnetic resonance imaging (rs-fMRI). Method Forty patients with TRD and forty healthy controls (HCs) were recruited. Rs-fMRI was performed before and after 30 min of taVNS at baseline. The brain regions that presented significantly different the Regional Homogeneity (ReHo) between the TRD patients and HCs were selected as the ROI to calculate the functional connectivity (FC) of full brain. The correlations were estimated between the clinical scales' score and the functional brain changes. Results Following taVNS stimulation treatment, TRD patients showed significantly reduced ReHo in the medial orbital frontal cortex (mOFC) (F = 18.06, P < 0.0001), ANCOVA of the mOFC-Based FC images revealed a significant interaction effect on the left inferior parietal gyrus (IPG) and left superior marginal gyrus (SMG) (F = 11.6615, P<0.001,F = 16.7520, P<0.0001). Among these regions, the HAMD and HAMA scores and ReHo/FC changes were not correlated. Conclusion This study applied rs-fMRI technology to examine the effect of taVNS stimulation treatment on the brain activity of TRD. These results suggest that the brain response of TRD patients to taVNS treatment may be associated with the functional modulation of cortical regions including the medial orbital frontal cortex, the left inferior parietal gyrus, and the left superior marginal regions. Changes in these neuroimaging indices may represent the neural mechanisms underlying taVNS Immediate Stimulation treatment in TRD.
Alternative splicing of Arabidopsis G6PD5 recruits NADPH-producing OPPP reactions to the endoplasmic reticulum

Glucose-6-phosphate dehydrogenase is the rate-limiting enzyme of the oxidative pentose-phosphate pathway (OPPP). The OPPP mainly provides NADPH and sugar-phosphate building blocks for anabolic pathways and is present in all eukaryotes. In plant cells, the irreversible part of the OPPP is found in several compartments. Among the isoforms catalyzing the first OPPP step in Arabidopsis, G6PD1 to G6PD4 target plastids (with G6PD1 being also directed to peroxisomes), whereas G6PD5 and G6PD6 operate in the cytosol. We noticed that alternative splice forms G6PD5.4 and G6PD5.5 encode N-terminally extended proteoforms. Compared to G6PD5.1, RT-PCR signals differed and fluorescent reporter fusions expressed in Arabidopsis protoplasts accumulated in distinct intracellular sites. Co-expression with organelle-specific markers revealed that the G6PD5.4 and G6PD5.5 proteoforms label different subdomains of the endoplasmic reticulum (ER), and analysis of C-terminal roGFP fusions showed that their catalytic domains face the cytosol. In g6pd5-1 g6pd6-2 mutant protoplasts lacking cytosolic G6PDH activity, the ER-bound proteoforms were both active and thus able to form homomers. Among the Arabidopsis 6-phosphogluconolactonases (catalyzing the second OPPP step), we noticed that isoform PGL2 carries a C-terminal CaaX motif that may be prenylated for membrane attachment. Reporter-PGL2 fusions co-localized with G6PD5.4 in ER subdomains, which was abolished by Cys-to-Ser exchange in the 256CSIL motif. Among the Arabidopsis 6-phosphogluconate dehydrogenases (catalyzing the third OPPP step), S-acylated peptides were detected for all three isoforms in a recent palmitoylome, with dual cytosolic/peroxisomal PGD2 displaying three sites. Co-expression of GFP-PGD2 diminished crowding of OFP-G6PD5.4 at the ER, independent of PGL2's presence. Upon pull-down of GFP-G6PD5.4, not only unlabeled PGD2 and PGL2 were enriched, but also enzymes that depend on NADPH provision at the ER, indicative of physical interaction with the OPPP enzymes. When membrane-bound G6PD5.5 and 5.4 variants were co-expressed with KCR1 (ketoacyl-CoA reductase, involved in fatty acid elongation), ATR1 (NADPH:cytochrome-P450 oxidoreductase), or pulled C4H/CYP73A5 (cinnamate 4-hydroxylase) as indirectly (via ATR) NADPH-dependent cytochrome P450 enzyme, co-localization in ER subdomains was observed. Thus, alternative splicing of G6PD5 can direct the NADPH-producing OPPP reactions to the cytosolic face of the ER, where they may operate as membrane-bound metabolon to support several important biosynthetic pathways of plant cells.
Orthogonal polynomials with hermitian matrix argument and associated semigroups

In this work we construct and study families of generalized orthogonal polynomials with hermitian matrix argument associated to a family of orthogonal polynomials on R. Different normalizations for these polynomials are considered and we obtain some classical formulas for orthogonal polynomials from the corresponding formulas for the one–dimensional polynomials. We also construct semigroups of operators associated to the generalized orthogonal polynomials and we give an expression of the infinitesimal generator of this semigroup and, in the classical cases, we prove that this semigroup is also Markov. For d–dimensional Jacobi expansions we study the notions of fractional integral (Riesz potentials), Bessel potentials and fractional derivatives. We present a novel decomposition of the L2 space associated with the d–dimensional Jacobi measure and obtain an analogous of Meyer's multiplier theorem in this setting. Sobolev Jacobi spaces are also studied.
Lactobacillus acidophilus novel strain, MJCD175, as a potential probiotic for oral health in dogs

The oral cavity is the second-largest habitat for microorganisms, and a well-balanced oral microbiome contributes to preventing dental disorders caused by pathogenic bacteria. Since humans and dogs have different lifestyles and oral microbiome structures, the present study aimed to develop novel probiotics for dogs. A total 53 Lactobacillus spp. were isolated from healthy dogs, and nine isolates were identified as Lactobacillus acidophilus according to 16S rRNA gene sequencing. According to the high antimicrobial activity against the dental caries-causing bacterium Streptococcus mutans, single or three mixed strains were orally administered to dogs for 4 weeks with concentration of 108-109 CFU/day. Intraoral swab samples were collected before and after the administration, and changes of oral pathogen were analyzed using quantitative PCR. Among them, Porphyromonas gingivalis, a critical factor of periodontitis, was significantly reduced in the single-strain administered group. Based on the acid and bile salts tolerance characteristics of isolates, systemic effects were also analyzed by comparing serum immunoglobulin and reproductive ability before and after the administration. However, no significant changes were observed in the serum IgG level and sperm quality. Overall, these in vitro and in vivo results suggest that L. acidophilus isolates from dogs, especially L. acidophilus MJCD175, could be promising probiotic candidates to support oral health without systemic adverse effects in dogs.
Invariant Subspace Method and Fractional Modified Kuramoto-Sivashinsky Equation

In this paper, the invariant subspace method is applied to the time fractional modified Kuramoto-Sivashinsky partial differential equation. The obtained reduced system of nonlinear ordinary fractional equations is solved by the Laplace transform method and with using of some useful properties of Mittag-Leffler function. Then, some exact solutions of the time fractional nonlinear studied equation are found.