Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA-138 improves LPS-induced trophoblast dysfunction through targeting RELA and NF-κB signaling

ABSTRACT Preeclampsia is a pregnancy complication classified by new onset of elevated blood pressure and proteinuria after 20 weeks of gestation. During preeclampsia, extra villous trophoblasts fail to adequately invade the myometrial spiral arteries, leading to incomplete and impaired vessel transformation and initiating or aggravating preeclampsia. Although NF-κB and proinflammatory cytokines have been reported to be related to trophoblast dysfunction, the underlying mechanism remains unclear. Herein, we demonstrated the miR-138/RELA axis modulating the migratory ability, and invasive ability of HTR-8/SVneo and JEG-3 cells, as well as the inflammatory factor levels in response to LPS stimulation. miR-138 expression was upregulated in preeclampsia placenta and LPS-stimulated HTR-8/SVneo and JEG-3 cell lines. miR-138 overexpression rescued the migratory and invasive ability of HTR-8/SVneo and JEG-3 cells inhibited by LPS stimulation, and decreased LPS-induced TNF-α and IL-6 levels. By binding the 3’-UTR of RELA, miR-138 negatively regulated p65 expression. The silencing of p65 also improved LPS-induced HTR-8/SVneo and JEG-3 cell dysfunction and TNF-α and IL-6 levels. More importantly, p65 overexpression partially reversed the functions of miR-138 overexpression upon both cells, indicating that miR-138 exerted its biological effects through targeting RELA. In conclusion, miR-138 improves LPS-induced inflammation and oxidative stress on trophoblasts through targeting RELA and affecting NF-κB signaling. The miR-138/RELA axis might be involved in preeclampsia pathogenesis, which requires further in vivo and clinical researches.
Maximal Oxygen Consumption Requirements in Professional North American Ice Hockey

Abstract Ferland, P-M, Marcotte-L'Heureux, V, Roy, P, Carey, V, Charron, J, Lagrange, S, Leone, M, and Comtois, AS. Maximal oxygen consumption requirements in professional North American ice hockey. J Strength Cond Res 35(4): 1586–1592, 2021—This study was designed to measure preseason on-ice relative V̇o2max of professional ice-hockey players (n = 101 National Hockey League [NHL], 42 American Hockey League [AHL], 4 East Coast Hockey League [ECHL], and 15 Canadian Hockey League [CHL]) throughout 17 years and compare it between generations, league level, and position, and to verify if it was related to season and NHL career statistics. Relative V̇o2max was measured on ice with a portable metabolic analyzer (K4b2, Cosmed, Rome) with full hockey equipment, except for the helmet with either the Skating Multistage Aerobic Test or the 30–15 intermittent ice test tests. Relative V̇o2max results from both tests were compared between players of the same generation with an independent-samples T-test and were not significantly different. A one-way analysis of variance and post hoc pairwise tests were performed to detect significant differences between groups. Pearson correlations (two-tailed) were also performed between selected variables. All statistical significance was set at p < 0.05. Results show that there are no significant differences for relative V̇o2max between generations (2001–2003 vs. 2006 vs. 2015–2017), league level (NHL vs. AHL vs. ECHL vs. CHL), and position (winger, center, and defense), other than the ECHL being lower. There are also no significant relationships between V̇o2max values and hockey season and NHL career statistics. Thus, the results show that there is a minimal relative V̇o2max requirement to play North American ice hockey at the elite level (55.9 ± 5.2 ml·kg−1·min−1; n = 162). Future research should be directed toward comparing V̇o2max of elite and amateur ice-hockey players to confirm the minimal relative V̇o2max requirement to play North American ice hockey at the elite level.
A new silyl Ether-type linker useful for the automated synthesis of oligonucleotides having base-labile protective groups

A new silyl-type linker for the automated solid-phase synthesis of oligodeoxynucleotides was developed. A hydrosilane-type reagent for introduction of the silyl linker was synthesized in an overall yield of 50% from 1,4-dibromobenzene. By using this linker, an oligonucleotide having base-labile protecting groups could be isolated from the controlled pore glass under neutral conditions.
Brown Adipose Tissue and Its Role in Insulin and Glucose Homeostasis

The increased worldwide prevalence of obesity, insulin resistance, and their related metabolic complications have prompted the scientific world to search for new possibilities to combat obesity. Brown adipose tissue (BAT), due to its unique protein uncoupling protein 1 (UPC1) in the inner membrane of the mitochondria, has been acknowledged as a promising approach to increase energy expenditure. Activated brown adipocytes dissipate energy, resulting in heat production. In other words, BAT burns fat and increases the metabolic rate, promoting a negative energy balance. Moreover, BAT alleviates metabolic complications like dyslipidemia, impaired insulin secretion, and insulin resistance in type 2 diabetes. The aim of this review is to explore the role of BAT in total energy expenditure, as well as lipid and glucose homeostasis, and to discuss new possible activators of brown adipose tissue in humans to treat obesity and metabolic disorders.
Antioxidants Promote Intestinal Tumor Progression in Mice

Dietary antioxidants and supplements are widely used to protect against cancer, even though it is now clear that antioxidants can promote tumor progression by helping cancer cells to overcome barriers of oxidative stress. Although recent studies have, in great detail, explored the role of antioxidants in lung and skin tumors driven by RAS and RAF mutations, little is known about the impact of antioxidant supplementation on other cancers, including Wnt-driven tumors originating from the gut. Here, we show that supplementation with the antioxidants N-acetylcysteine (NAC) and vitamin E promotes intestinal tumor progression in the ApcMin mouse model for familial adenomatous polyposis, a hereditary form of colorectal cancer, driven by Wnt signaling. Both antioxidants increased tumor size in early neoplasias and tumor grades in more advanced lesions without any impact on tumor initiation. Importantly, NAC treatment accelerated tumor progression at plasma concentrations comparable to those obtained in human subjects after prescription doses of the drug. These results demonstrate that antioxidants play an important role in the progression of intestinal tumors, which may have implications for patients with or predisposed to colorectal cancer.
The Krüppel-like factor Cabut has cell cycle regulatory properties similar to E2F1

Significance We discovered that the Drosophila transcription factor, Cabut, an ortholog of human KLF-10 and KLF-11, is capable of trans-activating a large set of cell cycle genes that are also E2F1 targets. Thereby, Cabut can drive ectopic cell cycles in many Drosophila cell types. That Cabut has E2F-like activity is especially interesting when one considers that the E2Fs, which are the best characterized transcriptional regulators of the eukaryotic cell cycle, are not actually essential for cell cycle gene transcription or cell cycle progression. Hence, it is clear that other transcription factors must also regulate the transcription of the 300 to 400 genes necessary for DNA replication and mitosis. Cabut appears to be one these missing transcription factors that can complement E2F. Using a gain-of-function screen in Drosophila, we identified the Krüppel-like factor Cabut (Cbt) as a positive regulator of cell cycle gene expression and cell proliferation. Enforced cbt expression is sufficient to induce an extra cell division in the differentiating fly wing or eye, and also promotes intestinal stem cell divisions in the adult gut. Although inappropriate cell proliferation also results from forced expression of the E2f1 transcription factor or its target, Cyclin E, Cbt does not increase E2F1 or Cyclin E activity. Instead, Cbt regulates a large set of E2F1 target genes independently of E2F1, and our data suggest that Cbt acts via distinct binding sites in target gene promoters. Although Cbt was not required for cell proliferation during wing or eye development, Cbt is required for normal intestinal stem cell divisions in the midgut, which expresses E2F1 at relatively low levels. The E2F1-like functions of Cbt identify a distinct mechanism for cell cycle regulation that may be important in certain normal cell cycles, or in cells that cycle inappropriately, such as cancer cells.
A Novel Adaptive Parameter Search Elastic Net Method for Fluorescent Molecular Tomography

Fluorescence molecular tomography (FMT) is a new type of medical imaging technology that can quantitatively reconstruct the three-dimensional distribution of fluorescent probes in vivo. Traditional Lp norm regularization techniques used in FMT reconstruction often face problems such as over-sparseness, over-smoothness, spatial discontinuity, and poor robustness. To address these problems, this paper proposes an adaptive parameter search elastic net (APSEN) method that is based on elastic net regularization, using weight parameters to combine the L1 and L2 norms. For the selection of elastic net weight parameters, this approach introduces the L0 norm of valid reconstruction results and the L2 norm of the residual vector, which are used to adjust the weight parameters adaptively. To verify the proposed method, a series of numerical simulation experiments were performed using digital mice with tumors as experimental subjects, and in vivo experiments of liver tumors were also conducted. The results showed that, compared with the state-of-the-art methods with different light source sizes or distances, Gaussian noise of 5%–25%, and the brute-force parameter search method, the APSEN method has better location accuracy, spatial resolution, fluorescence yield recovery ability, morphological characteristics, and robustness. Furthermore, the in vivo experiments demonstrated the applicability of APSEN for FMT.
A Crucial Role of ACBD3 Required for Coxsackievirus Infection in Animal Model Developed by AAV-Mediated CRISPR Genome Editing Technique

Genetic screens using CRISPR/Cas9 have been exploited to discover host–virus interactions. These screens have identified viral dependencies on host proteins during their life cycle and potential antiviral strategies. The acyl-CoA binding domain containing 3 (ACBD3) was identified as an essential host factor for the Coxsackievirus B3 (CVB3) infection. Other groups have also investigated the role of ACBD3 as a host factor for diverse enteroviruses in cultured cells. However, it has not been tested if ACBD3 is required in the animal model of CVB3 infection. Owing to embryonic lethality, conventional knockout mice were not available for in vivo study. As an alternative approach, we used adeno-associated virus (AAV)-mediated CRISPR genome editing to generate mice that lacked ACBD3 within the pancreas, the major target organ for CVB3. Delivery of sgRNAs using self-complementary (sc) AAV8 efficiently induced a loss-of-function mutation in the pancreas of the Cas9 knock-in mice. Loss of ACBD3 in the pancreas resulted in a 100-fold reduction in the CVB3 titer within the pancreas and a noticeable reduction in viral protein expression. These results indicate a crucial function of ACBD3 in CVB3 infection in vivo. AAV-mediated CRISPR genome editing may be applicable to many in vivo studies on the virus–host interaction and identify a novel target for antiviral therapeutics.
Influence of manufacturing parameters on gear distortion

Realising the system‐oriented approach of “Distortion Engineering”, the influence of multiple parameters on the distortion of cylindrical gears was investigated by design of experiments. Aim of this research work was to investigate the effect of production parameters before the final heat treatment. The established experimental design focuses on the analysis of two main parts of gear distortion. One part is the distortion of the teeth themselves; the other part is a displacement of the teeth due to the distortion of the disk‐shaped base body. The selection of the varied parameters is partly based on results of a system‐oriented experiment with disks. Therefore several influences on the base body distortion are known. In comparison to the analysis of disk distortion the interpretation of gear distortion measurements requires significantly extended effort. Besides a determination of the distortion of the complex involute tooth profile, it has to be distinguished between a change of the tooth profile and a change of the base body.
Irritant contact dermatitis following extracorporeal shockwave therapy: a case report.

Extracorporeal shockwave therapy (ESWT) has been widely used in the treatment of various musculoskeletal disorders with remarkable efficacy, with no relevant severe complications being reported. In this study, we report a rare case of acute irritant contact dermatitis following ESWT with serious skin damage, which has never been previously reported. A 42-year-old male patient with osteonecrosis of the femoral head (ONFH) was subjected to two sessions of ESWT. In the first session of low-energy ESWT (0.15 mJ/mm2 , 3 Hz, and a total of 2,000 impulses), no local or systematic adverse reactions occurred. Three months later, he was subjected to a second session of high-energy ESWT (0.28 mJ/mm2 , 4 Hz, and a total of 2,000 impulses). However, on the second day, the patient presented with itching and painful erythema and blisters on the local skin of the hip. Based on these manifestations and the results of patch testing, the patient was diagnosed with irritant contact dermatitis and treated by an oral antihistamine combined with external calamine lotions. The skin lesions began to develop exudate from erosion and scabs had gradually formed with treatment, and finally dry scabs fell off with no scar left. This is the first reported irritant contact dermatitis after ESWT. Although bone pathologies should be treated with high energy, patients should be informed of this potential rare complication.
Antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities of pentacyclic triterpenes isolated from Ziziphus oxyphylla Edgew

Abstract Ziziphus oxyphylla Edgew is in folk use in Pakistan as an analgesic, anti-inflammatory, and liver ailments. Therefore, we have investigated antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities of the isolated compounds (ceanothic acid and zizybrenalic acid) from the chloroform fraction of Z. oxyphylla. Ceanothic acid and zizybrenalic acid showed significant DPPH and H2O2 scavenging activity as compared to control. In the acute toxicity study, ceanothic acid and zizybrenalic acid showed no toxic effects upto 200 mg/kg. The antinociceptive activity shown by ceanothic acid and zizybrenalic acid at 50 mg/kg was 64.28% and 65.35% compared to diclofenac sodium (72.3%) at 50 mg/kg. The percent inhibition of xylene-induced ear edema exhibited by ceanothic acid and zizybrenalic acid at 50 mg/kg was 51.33% and 58.66%, respectively, as compared to diclofenac sodium (72.66%). Both the isolated compounds exhibited inhibition of carrageenan-induced paw edema as compared to control. Hepatoprotection exhibited by zizybrenalic acid was more pronounced than ceanothic acid as observed from the decrease in carbon tetrachloride (CCl4)-induced elevation of serum biomarkers, antioxidant enzymes and lipid peroxidation. Furthermore, zizybrenalic acid produced a marked decline in CCl4-induced prolongation of phenobarbital-induced sleeping duration. Zizybrenalic acid exhibited 55.4 ± 1.37% inhibition of hypotonic solution-induced hemolysis compared to sodium salicylate (75.6 ± 2.15%). The histopathological damage caused by CCl4 was also countered by the administration of ceanothic acid and zizybrenalic acid. Ceanothic acid and zizybrenalic acid exhibited antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities. Zizybrenalic acid exhibited better antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activity than ceanothic acid.
Insomnia symptoms and biomarkers of monocyte activation, systemic inflammation, and coagulation in HIV: Veterans Aging Cohort Study

Background Insomnia may be a risk factor for cardiovascular disease in HIV (HIV-CVD); however, mechanisms have yet to be elucidated. Methods We examined cross-sectional associations of insomnia symptoms with biological mechanisms of HIV-CVD (immune activation, systemic inflammation, and coagulation) among 1,542 people with HIV from the Veterans Aging Cohort Study (VACS) Biomarker Cohort. Past-month insomnia symptoms were assessed by the item, “Difficulty falling or staying asleep? ,” with the following response options: “I do not have this symptom” or “I have this symptom and…” “it doesn’t bother me,” “it bothers me a little,” “it bothers me,” “it bothers me a lot. ” Circulating levels of the monocyte activation marker soluble CD14 (sCD14), inflammatory marker interleukin-6 (IL-6), and coagulation marker D-dimer were determined from blood specimens. Demographic- and fully-adjusted (CVD risk factors, potential confounders, HIV-related factors) regression models were constructed, with log-transformed biomarker variables as the outcomes. We present the exponentiated regression coefficient (exp[b]) and its 95% confidence interval (CI). Results We observed no significant associations between insomnia symptoms and sCD14 or IL-6. For D-dimer, veterans in the “Bothers a Lot” group had, on average, 17% higher D-dimer than veterans in the “No Difficulty Falling or Staying Asleep” group in the demographic-adjusted model (exp[b] = 1.17, 95%CI = 1.01–1.37, p = .04). This association was nonsignificant in the fully-adjusted model (exp[b] = 1.09, 95%CI = 0.94–1.26, p = .27). Conclusion We observed little evidence of relationships between insomnia symptoms and markers of biological mechanisms of HIV-CVD. Other mechanisms may be responsible for the insomnia-CVD relationship in HIV; however, future studies with comprehensive assessments of insomnia symptoms are warranted.
Quantum‐dot size‐distribution analysis and precipitation stages in semiconductor doped glasses

The sequence of stages during precipitation of semiconductor (e.g., CdS, CdSe) clusters from supersaturated glasses exhibiting quantum‐confinement effects was investigated. The rate of formation of nanometer‐size ‘‘quantum dots’’ distributed in a continuous glass matrix is critically determined by the time and temperature of the heat treatment given to the quenched glasses. The entire precipitation process was analyzed in terms of several decomposition stages: nucleation, normal growth, coalescence of quantum dots, and devitrification of the glass matrix itself. Experimental data obtained by differential thermal analysis were utilized to identify the heat‐treatment temperature range associated with the precipitation stages. The size distribution of CdSe quantum‐dot clusters was analyzed using our transmission electron microscopy data. The data of Ekimov et al. [Solid State Commun. 56, 921 (1975)] was reduced to time‐temperature master plots useful for precipitating quantum dots of a given size in glasses.
U.S. Montmorency Tart Cherry Juice Decreases Bone Resorption in Women Aged 65–80 Years

Pre-clinical studies have demonstrated that tart cherries, rich in hydroxycinnamic acids and anthocyanins, protect against age-related and inflammation-induced bone loss. This study examined how daily consumption of Montmorency tart cherry juice (TC) alters biomarkers of bone metabolism in older women. Healthy women, aged 65–80 years (n = 27), were randomly assigned to consume ~240 mL (8 fl. oz.) of juice once (TC1X) or twice (TC2X) per day for 90 d. Dual-energy x-ray absorptiometry (DXA) scans were performed to determine bone density at baseline, and pre- and post-treatment serum biomarkers of bone formation and resorption, vitamin D, inflammation, and oxidative stress were assessed. Irrespective of osteoporosis risk, the bone resorption marker, tartrate resistant acid phosphatase type 5b, was significantly reduced with the TC2X dose compared to baseline, but not with the TC1X dose. In terms of indicators of bone formation and turnover, neither serum bone-specific alkaline phosphatase nor osteocalcin were altered. No changes in thiobarbituric acid reactive substances or high sensitivity C-reactive protein were observed in response to either TC1X or TC2X. We conclude that short-term supplementation with the higher dose of tart cherry juice decreased bone resorption from baseline without altering bone formation and turnover biomarkers in this cohort.
Killing HIV-infected resting central memory CD4+ T cells by targeting inhibitor of apoptosis proteins-inhibited autophagy

Dysfunction of CD4+ T cells by HIV infection can cause serious immune defects. Recently, Campbell and colleagues described an intriguing and simple therapeutic method for HIV-infected resting central memory CD4+ T cells (HIV-TCM), dependently on inhibitor of apoptosis (IAP) family proteins-targeted and second mitochondria-derived activator of caspases (SMAC) mimetics-mediated apoptosis, which is only triggered in HIV-TCM and not uninfected ones. Autophagy induction and subsequent formation of a ripoptosome-like death signaling complex were observed after such treatment, which may partially explain the potential mechanism. However, the direct intracellular inhibitory effects of IAPs on autophagy, as well as the critical roles of autophagy in activating extracellular anti-infection immune responses, warrant further investigation. Thus, this pointer aims to provide potential alternative mechanisms and to suggest important avenues for follow-up study.
Case Report: Therapeutic Threshold for Rifampicin-Resistant Tuberculosis in a Patient from Maputo, Mozambique

ABSTRACT We present a case of a patient in Mozambique, who initiated treatment for rifampicin-resistant tuberculosis (RR-TB) without proof of resistance. For this patient, we estimated the probability of RR-TB using likelihood ratios of clinical arguments. The probability of RR-TB in Mozambique, positive HIV status, and treatment failure after a first treatment and after retreatment were included as confirming arguments, and a rapid molecular test showing rifampicin susceptibility as excluding argument. The therapeutic threshold to start treatment for RR-TB is unknown, but probably lower than 47% and should be calculated to guide clinical decisions.
A Novel Sparse Graph-Regularized Singular Value Decomposition Model and Its Application to Genomic Data Analysis

Learning the gene coexpression pattern is a central challenge for high-dimensional gene expression analysis. Recently, sparse singular value decomposition (SVD) has been used to achieve this goal. However, this model ignores the structural information between variables (e.g., a gene network). The typical graph-regularized penalty can be used to incorporate such prior graph information to achieve more accurate discovery and better interpretability. However, the existing approach fails to consider the opposite effect of variables with negative correlations. In this article, we propose a novel sparse graph-regularized SVD model with absolute operator (AGSVD) for high-dimensional gene expression pattern discovery. The key of AGSVD is to impose a novel graph-regularized penalty ( $| \boldsymbol {u}|^{T} \boldsymbol {L}| \boldsymbol {u}|$ ). However, such a penalty is a nonconvex and nonsmooth function, so it brings new challenges to model solving. We show that the nonconvex problem can be efficiently handled in a convex fashion by adopting an alternating optimization strategy. The simulation results on synthetic data show that our method is more effective than the existing SVD-based ones. In addition, the results on several real gene expression data sets show that the proposed methods can discover more biologically interpretable expression patterns by incorporating the prior gene network.