Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vitro Effect of CCL11 on Myogenic Differentiation and Its Relevance With Sarcopenia Parameters in Older Adults

Abstract Background: The C-C motif chemokine ligand 11 (CCL11) has been receiving attention as a potential pro-aging factor and thus may be also involved in muscle metabolism and sarcopenia, a key component of aging phenotypes. To clarify this possibility, we investigated the effects of CCL11 on in vitro muscle biology and clinical relevance with sarcopenia parameters in older adults. Methods: Primary mouse myoblasts and C2C12 cells were used for experimental research. Blood samples were collected from 79 participants who underwent a functional assessment, and CCL11 level was measured using a quantikine ELISA kit. Sarcopenia was diagnosed using the Asian-specific cut-off points. Results: CCL11 treatment stimulated the differentiation of both primary myoblasts and C2C12 cells into mature myotubes, and consistently increased the expression of myogenic differentiation markers, such as myosin heavy chain and myogenin. Among C-C chemokine receptors (CCRs), CCR5, not CCR2 and CCR3, was predominantly expressed in muscle cells, and CCR5 inhibitor blocked CCL11-stimulated myogenesis. In a clinical study, after adjustment for sex, age, and body mass index, serum CCL11 level was not significantly different according to the status of sarcopenia, low muscle mass, low muscle strength, and low physical performance, and was not associated with any of skeletal muscle index, grip strength, gait speed, time to complete 5 chair stands, and short physical performance battery score. Conclusions: Contrary to expectations, CCL11 showed the beneficial effects on muscle metabolism at least in vitro system. However, the role of CCL11 on muscle health in humans was not evident, suggesting that circulating CCL11 level may not be a useful biomarker for sarcopenia risk assessment in older adults.
Characterization of the complete mitochondrial genome of Omosita colon (Coleoptera: Nitidulidae)

Abstract Omosita colon (Linnaeus, 1758) (Coleoptera: Nitidulidae) is an economically important storage pest worldwide and a forensically important beetle. The first complete mitochondrial genome (mitogenome) of O. colon was sequenced in this study using the next-generation sequencing. The mitogenome of O. colon is circular with a total length of 16,544 bp, which consists of 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and a non-coding control region. The order and orientation of genes were identical with that of the ancestral insects. This study provides genomic data for mitogenome library of the genus Omosita to investigate evolutionary and systematic studies. It also provides a molecular basis to infer the postmortem interval (PMImin) with O. colon.
INTERNATIONAL CENTRE FOR ECONOMIC RESEARCH

This paper studies the hedging problem of life insurance policies, when the mortality and interest rates are stochastic. We focus primarily on stochastic mortality. We represent death arrival as the first jump time of a doubly stochastic process, i.e. a jump process with stochastic intensity. We propose a Delta-Gamma Hedging technique for mortality risk in this context. The risk factor against which to hedge is the difference between the actual mortality intensity in the future and its ”forecast” today, the instantaneous forward intensity. We specialize the hedging technique first to the case in which survival intensities are affine, then to Ornstein-Uhlenbeck and Feller processes, providing actuarial justifications for this restriction. We show that, without imposing no arbitrage, we can get equivalent probability measures under which the HJM condition for no arbitrage is satisfied. Last, we extend our results to the presence of both interest rate and mortality risk, when the forward interest rate follows a constant-parameter Hull and White process. We provide a UK calibrated example of Delta and Gamma Hedging of both mortality and interest rate risk.
BRET analysis reveals interaction between the lysophosphatidic acid receptor LPA2 and the lysophosphatidylinositol receptor GPR55 in live cells

Lysophosphatidic acid (LPA) and lysophosphatidylinositol bind to the G protein‐coupled receptors (GPCRs) LPA and GPR55, respectively. LPA2, a type 2 LPA receptor, and GPR55 are highly expressed in colon cancer and involved in cancer progression. However, crosstalk between the two receptors and potential effects on cellular physiology are not fully understood. Here, using BRET analysis, we found that LPA2 and GPR55 interact in live cells. In the presence of both receptors, LPA2 and/or GPR55 activation facilitated co‐internalization, and activation of GPR55, uncoupled with Gαi, induced reduction of intracellular cAMP. Notably, co‐activation of receptors synergistically triggered further decline in the cAMP level, promoted cell proliferation, and increased the expression of cancer progression‐related genes, suggesting that physical and functional crosstalk between LPA2 and GRR55 is involved in cancer progression.
Optimization, and in vitro and in vivo evaluation of etomidate intravenous lipid emulsion

Abstract The aim of this investigation was to develop an etomidate intravenous lipid emulsion (ETM-ILE) and evaluate its properties in vitro and in vivo. Etomidate (ETM) is a hydrophobic drug, and organic solvents must be added to an etomidate injectable solution (ETM-SOL) to aid dissolution, that causes various adverse reactions on injection. Lipid emulsions are a novel drug formulation that can improve drug loading and reduce adverse reactions. ETM-ILE was prepared using high-pressure homogenization. Univariate experiments were performed to select key conditions and variables. The proportion of oil, egg lecithin, and poloxamer 188 (F68) served as variables for the optimization of the ETM-ILE formulation by central composite design response surface methodology. The optimized formulation had the following characteristics: particle size, 168.0 ± 0.3 nm; polydispersity index, 0.108 ± 0.028; zeta potential, −36.4 ± 0.2 mV; drug loading, 2.00 ± 0.01 mg/mL; encapsulation efficiency, 97.65% ± 0.16%; osmotic pressure, 292 ± 2 mOsmol/kg and pH value, 7.63 ± 0.07. Transmission electron microscopy images showed that the particles were spherical or spheroidal, with a diameter of approximately 200 nm. The stability study suggested that ETM-ILE could store at 4 ± 2 °C or 25 ± 2 °C for 12 months. Safety tests showed that ETM-ILE did not cause hemolysis or serious vascular irritation. The results of the pharmacokinetic study found that ETM-ILE was bioequivalent to ETM-SOL. However, a higher concentration of ETM was attained in the liver, spleen, and lungs after administration of ETM-ILE than after administration of ETM-SOL. This study found that ETM-ILE had great potential for clinical applications.
Loading mechanisms of the anterior cruciate ligament

ABSTRACT This review identifies the three-dimensional knee loads that have the highest risk of injuring the anterior cruciate ligament (ACL) in the athlete. It is the combination of the muscular resistance to a large knee flexion moment, an external reaction force generating knee compression, an internal tibial torque, and a knee abduction moment during a single-leg athletic manoeuvre such as landing from a jump, abruptly changing direction, or rapidly decelerating that results in the greatest ACL loads. While there is consensus that an anterior tibial shear force is the primary ACL loading mechanism, controversy exists regarding the secondary order of importance of transverse-plane and frontal-plane loading in ACL injury scenarios. Large knee compression forces combined with a posteriorly and inferiorly sloped tibial plateau, especially the lateral plateau—an important ACL injury risk factor—causes anterior tibial translation and internal tibial rotation, which increases ACL loading. Furthermore, while the ACL can fail under a single supramaximal loading cycle, recent evidence shows that it can also fail following repeated submaximal loading cycles due to microdamage accumulating in the ligament with each cycle. This challenges the existing dogma that non-contact ACL injuries are predominantly due to a single manoeuvre that catastrophically overloads the ACL.
POLYGALACTURONASE45 cleaves pectin and links cell proliferation and morphogenesis to leaf curvature in Arabidopsis thaliana.

Regulating plant architecture is a major goal in current breeding programs. Previous studies have increased our understanding of the genetic regulation of plant architecture, but it is also essential to understand how organ morphology is controlled at the cellular level. In the cell wall, pectin modification and degradation are required for organ morphogenesis, and these processes involve a series of pectin-modifying enzymes. Polygalacturonases are a major group of pectin-hydrolyzing enzymes that cleave pectin backbones and release oligogalacturonides. Polygalacturonase genes function in cell expansion and separation, and contribute to organ expansion, separation, and dehiscence in plants. However, whether and how they influence other cellular processes and organ morphogenesis are poorly understood. Here, we characterized the functions of Arabidopsis POLYGALACTURONASE45 (PG45) in organ morphogenesis using genetic, developmental, cell biological, and biochemical analyses. A heterologously expressed portion of PG45 cleaves pectic homogalacturonan in vitro, indicating that PG45 is a bona fide polygalacturonase. PG45 functions in leaf and flower structure, branch formation and organ growth. Undulation in pg45 knockout and PG45 overexpression leaves is accompanied by impaired adaxial-abaxial polarity, and loss of PG45 shortens the duration of cell proliferation in the adaxial epidermis of developing leaves. Abnormal leaf curvature is coupled with altered pectin metabolism and autogenous oligogalacturonide profiles in pg45 knockout and PG45 overexpression leaves. Together, these results highlight a previously underappreciated function for PGs in determining tissue polarity and regulating cell proliferation, and imply the existence of oligogalacturonide-based signaling pathways that modulate plant development.
Predicting survival in head and neck cancer: External validation and update of the prognostic model OncologIQ in 2189 patients

Abstract Background Disclosing prognostic information is necessary to enable patients to make well‐informed treatment decisions. OncologIQ is a prognostic model that predicts the overall survival (OS) probability in patients with head and neck squamous cell carcinoma (HNSCC). We aimed to externally validate and update the model with new prognostic factors and translate it to a clinically useful tool. Methods A consecutive retrospective sample of 2189 patients eligible for curative treatment of a primary HNSCC were selected. Discriminative performance was determined using the C‐statistic. Results External validation showed systematic underestimation of OS in the new population, and reasonable discrimination (C‐statistic 0.67). Adding smoking, pack years, BMI, weight loss, WHO performance, socioeconomic status, and p16 positivity to the recalibrated multivariable model, improved the internally validated C‐statistic to 0.71. The model showed minor optimism and was translated in an online tool (www.oncologiq.nl). Conclusions The updated model enables personalized patient counseling during treatment decision consultations.
Sinonasal carcinoma and Ohngren's line: Retrospective cohort study of 39 patients

Approximately two thirds of this study cohort displayed a sinonasal carcinoma extending across Ohngren's line at diagnosis. Tumor extension across Ohngren's line at diagnosis is a negative prognostic factor for clinical outcome in accordance with AJCC 8th edition. 90% of tumors presenting with retropharyngeal lymph node metastasis were extended across Ohngren's line at diagnosis. The presence of retropharyngeal lymph node metastasis is a strong negative prognosticator for survival in our study. Retropharyngeal lymph node metastasis at diagnosis may be considered for inclusion in tumor staging for sinonasal carcinoma.
Balancing HIV testing efficiency with HIV case-identification among children and adolescents (2–19 years) using an HIV risk screening approach in Tanzania

To optimize HIV testing resources, programs are moving away from universal testing strategies toward a risk-based screening approach to testing children/adolescents, but there is little consensus around what defines an optimal risk screening tool. This study aimed to validate a 12-item risk screening tool among children and adolescents and provide suggested fewer-item tool options for screening both facility out-patient and community populations by age strata (<10 and ≥10 years). Children/adolescents (2–19 years) with unknown HIV status were recruited from a community-based vulnerable children program and health facilities in 5 regions of Tanzania in 2019. Lay workers administered the screening questions to caregivers/adolescents; nurses enrolled those eligible for the study and tested all participants for HIV. For each screening item, we estimated sensitivity, specificity, positive predictive value and negative predictive value and associated 95% confidence intervals (CI). We generated a score based on the count of items with a positive risk response and fit a receiver operating characteristic curve to determine a cut-off score. Sensitivity, specificity, positive predictive value (PPV; yield) and number needed to test to detect an HIV-positive child (NNT) were estimated for various tool options by age group. We enrolled 21,008 children and adolescents. The proportion of undiagnosed HIV-positive children was low (n = 76; 0.36%; CI:0.29,0.45%). A screening algorithm based on reporting at least one or more items on the 10 to 12-item tool had sensitivity 89.2% (CI:79.1,95.6), specificity 37.5% (CI:36.8,38.2), positive predictive value 0.5% (CI:0.4,0.6) and NNT = 211. An algorithm based on at least two or more items resulted in lower sensitivity (64.6%), improved specificity (69.1%), PPV (0.7%) and NNT = 145. A shorter tool derived from the 10 to 12-item screening tool with a score of “1” or more on the following items: relative died, ever hospitalized, cough, family member with HIV, and sexually active if 10–19 years performed optimally with 85.3% (CI:74.6,92.7) sensitivity, 44.2% (CI:43.5,44.9) specificity, 0.5% (CI:0.4,0.7) PPV and NNT = 193. We propose that different short-tool options (3–5 items) can achieve an optimal balance between reduced HIV testing costs (lower NNT) with acceptable sensitivity. In low prevalence settings, changes in yield may be negligible and NNT may remain high even for an effective tool.
Disentangling the effects of CAD/CAM customized appliances and piezocision in orthodontic treatment: New evidence.

OBJECTIVES To discern the effects of computer-aided design (CAD)/computer-aided manufactured (CAM) customized appliances and piezocision on orthodontic treatment (OT). MATERIALS AND METHODS The study combined findings from two previously published randomized controlled trials: (1) standard OT vs piezocision-assisted standard OT, and (2) CAD/CAM OT vs piezocision-assisted CAD/CAM OT. Piezocision is a minimally invasive corticotomy surgical procedure used to accelerate orthodontic treatment and CAD/CAM refers to CAD/CAM customized brackets and archwires. The outcomes were the overall treatment time, and the durations of the alignment phase and fine-tuning phase. Clinical and radiological features also were evaluated. RESULTS The combined study included 48 patients with similar baseline characteristics. Compared to the standard treatment, CAD/CAM technology alone significantly decreased the overall median OT time from 543 to 394 days (P < .001) and from 543 to 254 days (P < .0001) when combined with piezocision. Although piezocision significantly reduced the duration of the alignment phase in the mandible and maxilla, CAD/CAM technology considerably shortened the fine-tuning phase. All periodontal and radiographic parameters remained stable from the start to the end of treatment in all groups. CONCLUSIONS CAD/CAM technology combined with piezocision accelerates the entire OT process, during the alignment phase for piezocision and during the fine-tuning phase for CAD/CAM, with a global reduction of the overall treatment time of more than 50%.
Dendritic cells support a proliferative antigen-specific T-cell response in the presence of poly(lactic-co-glycolic acid).

Biomaterials are known to modulate immune cell functions, which subsequently determine the host inflammatory and immune responses. Poly(lactic-co-glycolic acid) or PLGA, a biodegradable and biocompatible biomaterial, induces a pro-inflammatory, mature phenotype in antigen presentation cells, namely dendritic cells (DCs) in vitro. In vivo, PLGA can boost the humoral immune response to a co-delivered model antigen, a phenomenon known as the PLGA-adjuvant effect. This study elucidates the link between PLGA's effect on the DC phenotype in vitro and its adjuvant effect in vivo using the CD11c-DTR mouse model. These mice undergo conditional ablation of DCs upon treatment with diphtheria toxin. To measure immune activation, the mice were first given ovalbumin (OVA)-reactive T cells from OT-II/OT-I mice. Later, the same mice received subcutaneous OVA-loaded PLGA scaffold implants. In response to the scaffold implants, OVA-reactive OT-II CD4+ T cells showed decreased proliferation in the absence of CD11c+ DCs, indicating an attenuation of the PLGA-adjuvant effect. Furthermore, PLGA may also influence the antigen cross-presentation function of DCs, as evident with the lowered OVA-reactive OT-I CD8+ T-cell response. Understanding the immunomodulatory ability of biomaterials in the context of DCs will aid in designing improved DC-based immunotherapies against infectious diseases and cancer.
Intrasubunit and Intersubunit Steroid Binding Sites Independently and Additively Mediate α1β2γ2L GABAA Receptor Potentiation by the Endogenous Neurosteroid Allopregnanolone

Prior work employing functional analysis, photolabeling, and X-ray crystallography have identified three distinct binding sites for potentiating steroids in the heteromeric GABAA receptor. The sites are located in the membrane-spanning domains of the receptor at the β-α subunit interface (site I) and within the α (site II) and β subunits (site III). Here, we have investigated the effects of mutations to these sites on potentiation of the rat α1β2γ2L GABAA receptor by the endogenous neurosteroid allopregnanolone (3α5αP). The mutations were introduced alone or in combination to probe the additivity of effects. We show that the effects of amino acid substitutions in sites I and II are energetically additive, indicating independence of the actions of the two steroid binding sites. In site III, none of the mutations tested reduced potentiation by 3α5αP, nor did a mutation in site III modify the effects of mutations in sites I or II. We infer that the binding sites for 3α5αP act independently. The independence of steroid action at each site is supported by photolabeling data showing that mutations in either site I or site II selectively change steroid orientation in the mutated site without affecting labeling at the unmutated site. The findings are discussed in the context of linking energetic additivity to empirical changes in receptor function and ligand binding. SIGNIFICANCE STATEMENT Prior work has identified three distinct binding sites for potentiating steroids in the heteromeric γ-aminobutyric acid type A receptor. This study shows that the sites act independently and additively in the presence of the steroid allopregnanolone and provide estimates of energetic contributions made by steroid binding to each site.
Establishment of an Agrobacterium‐mediated genetic transformation and CRISPR/Cas9‐mediated targeted mutagenesis in Hemp (Cannabis Sativa L.)

Summary Hemp (Cannabis sativa L.) is an annual and typically dioecious crop. Due to the therapeutic potential for human diseases, phytocannabinoids as a medical therapy is getting more attention recently. Several candidate genes involved in cannabinoid biosynthesis have been elucidated using omics analysis. However, the gene function was not fully validated due to few reports of stable transformation for Cannabis tissues. In this study, we firstly report the successful generation of gene‐edited plants using an Agrobacterium‐mediated transformation method in C. sativa. DMG278 achieved the highest shoot induction rate, which was selected as the model strain for transformation. By overexpressing the cannabis developmental regulator chimera in the embryo hypocotyls of immature grains, the shoot regeneration efficiency was substantially increased. We used CRISPR/Cas9 technology to edit the phytoene desaturase gene and finally generated four edited cannabis seedlings with albino phenotype. Moreover, we propagated the transgenic plants and validated the stable integration of T‐DNA in cannabis genome.
Roles of Stra8 and Tcerg1l in retinoic acid induced spermatogonial differentiation in mouse

Abstract Retinoic acid (RA) induces spermatogonial differentiation, but the mechanism by which it operates remains largely unknown. We developed a germ cell culture assay system to study genes involved in spermatogonial differentiation triggered by RA. Stimulated by RA 8 (Stra8), a RA-inducible gene, is indispensable for meiosis initiation, and its deletion results in a complete block of spermatogenesis at the pre-leptotene/zygotene stage. To interrogate the role of Stra8 in RA mediated differentiation of spermatogonia, we derived germ cell cultures from the neonatal testis of both wild type and Stra8 knock-out mice. We provide the first evidence that Stra8 plays a crucial role in modulating the responsiveness of undifferentiated spermatogonia to RA and facilitates transition to a differentiated state. Stra8-mediated differentiation is achieved through the downregulation of a large portfolio of genes and pathways, most notably including genes involved in the spermatogonial stem cell self-renewal process. We also report here for the first time the role of transcription elongation regulator-1 like (Tcerg1l) as a downstream effector of RA-induced spermatogonial differentiation. Summary sentence The genes stimulated by retinoic acid 8 (Stra8) and transcription elongation regulator-1 like (Tcerg1l) are necessary in early-stage male germ cell differentiation induced by retinoic acid (RA). Stra8 is critical in modulating the responsiveness of undifferentiated spermatogonia to RA.
Heterocyclic amines formation and mitigation in processed meat and meat products: a review.

This review assesses heterocyclic amines (HCAs) formation and mitigation in processed meat and meat products. HCAs are formed when amino acids react with creatine during thermal processing of meat and meat products. The formation of HCAs depends on various factors, including the temperature and cooking time, fat contents, and the presence of HCA precursors, such as water, and lipids, meat marinating. Additional factors that could promote HCA formation are pH, meat type and ingredients added during cooking such as antioxidants, amino acids, ions, fat, and sugars that help in the production of HCAs. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8 dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), IQ, and MeIQ are HCAs of importance because of their link to cancer in humans. Over 25 different HCAs have been identified in processed food up to date. Out of this nine of the HCAs belong to possible carcinogens (group 2B) while one is grouped as a probable carcinogen (group 2A) in humans. To mitigate HCA generation during heat processing, different techniques have been used which include multiple recipes, adjustments of thermal processing conditions, the use of flavourings in case of meat, pre-treatments like microwave application, as well as application of antioxidants whether natural occurring and artificial ones.