Miracle-dz/UniFAR-FTUs huggingface dataset:
LncRNA ST8SIA6-AS1 Promotes Cholangiocarcinoma Progression by Suppressing the miR-145-5p/MAL2 Axis

Background The tumor-promoting roles of ST8SIA6-AS1 and miR-145-5p have been found in several cancers, but their function in cholangiocarcinoma (CHOL) remains speculative. The purpose of this study was to examine the regulatory functions of the ST8SIA6-AS1/MAL2/miR-145-5p pathway in CHOL progression. Methods RT-qPCR assay was used to detect ST8SIA6-AS1 expression in CHOL tissues and cell lines. Cell migration, apoptosis, invasion, and proliferation abilities were assessed by RIP, RNA pull-down, and luciferase assays. CCK-8, BrdU, transwell, and FITC assays to investigate the regulatory functions of ST8SIA6-AS1, miR-145-5p, and MAL2 function in CHOL cells. Results Findings revealed the enrichment of ST8SIA6-AS1 in CHOL tissues and cell lines. It was also found that ST8SIA6-AS1 facilitated cell growth and migration, but it reduced the apoptosis level of the CHOL cells. The results of experiments showed that ST8SIA6-AS1 sponged miR-145-5p, thereby allowing MAL2 to exert its biological function on CHOL cells. Conclusion This research suggested that the ST8SIA6-AS1/miR-145-5p/MAL2 axis could enhance CHOL progression, which might be useful to improve the clinical outcomes of CHOL patients.
Nisin-Loaded Ulvan Particles: Preparation and Characterization

Nisin is an attractive alternative to chemical preservatives in the food industry. It is a cationic peptide of 34 amino acid residues that exhibits antimicrobial activity against Gram-positive bacteria. To ensure nisin stability in food matrices, new nisin-loaded ulvan particles were developed by the complexation method. The interaction of nisin with ulvan was demonstrated by FT-IR spectroscopy and differential scanning calorimetry. The encapsulation efficiency was calculated at different pH values within the range of 4.0–7.0 and was found to have the highest value at pH 7.0. The size and surface charge of particles fabricated at different concentrations of nisin and pH values were determined. Nisin-loaded ulvan particles exhibited antimicrobial activity against Gram-positive bacteria comparable to that of free nisin. Therefore, the developed complexes have the potential for application as biopreservatives in the food industry. For the first time, the potential of ulvan as a carrier of antimicrobial agent nisin was demonstrated.
Lack of Association between Interarm Systolic Blood Pressure Difference and Coronary Artery Disease in Patients Undergoing Elective Coronary Angiography

Aim Peripheral vascular disease (PVD) and coronary artery disease (CAD) are, in many cases, asymptomatic and not usually diagnosed. The timely diagnosis of peripheral vascular diseases can act as an indicator or practical evidence of CAD. Therefore, this study was conducted to determine the relationship between interarm systolic blood pressure difference (IASBPD) and severity and number of coronary artery stenosis. Methods The samples in this cross-sectional study consisted of 578 patients who were candidates for coronary angiography, with an average age of 57.5 ± 10.5 years. Patients were classified according to CAD and number and severity of coronary artery stenosis. The relationship between IASBPD and presence or lack of CAD as well as the number and severity of coronary artery stenosis was studied. The sensitivity, specificity, and positive predictive value of IASBPD index were calculated for the detection of CAD using the Kappa coefficient. Results There was no statistically significant relationship between IASBPD, CAD, and severity and number of coronary artery stenosis. This index had low sensitivity and predictive value in the diagnosis of CAD and stenosis in coronary arteries in comparison with angiography. Conclusion The results showed that the IASBPD index cannot be a valid criterion for the diagnosis of CAD as well as the number and severity of coronary artery stenosis. More studies with larger sample sizes and different designs are needed in this regard to achieve more conclusive results.
Characterization and Regulation of the Acetolactate Synthase Genes Involved in Acetoin Biosynthesis in Acetobacter pasteurianus

Acetoin is an important aroma-active chemical in cereal vinegars. Acetobacter pasteurianus was reported to make a significant contribution to acetoin generation in cereal vinegars. However, the related acetoin biosynthesis mechanism was largely unknown. Two annotated acetolactate synthase (ALS) genes of A. pasteurianus were investigated in this study to analyze their functions and regulatory mechanisms. Heterologous expression in Escherichia coli revealed that only AlsS1 exhibited ALS activity and had the optimal activity at 55 °C and pH 6.5. Two alsS-defective mutants of A. pasteurianus CICC 22518 were constructed, and their acetoin yields were both reduced, suggesting that two alsS genes participated in acetoin biosynthesis. A total 79.1% decrease in acetoin yield in the alsS1-defective mutant revealed that alsS1 took a major role. The regulator gene alsR disruptant was constructed to analyze the regulation effect. The decline of the acetoin yield and down-regulation of the alsD and alsS1 gene transcriptions were detected, but the alsS2 gene transcription was not affected. Acetoin was an important metabolite of lactate catabolism in A. pasteurianus. The coexistence of two alsS genes can help strains rapidly and securely assimilate lactate to deal with the lactate pressure in a vinegar brewing environment, which represented a new genetic mode of acetoin production in bacteria.
Hsa-miR-125b Therapeutic Role in Colon Cancer Is Dependent on the Mutation Status of the TP53 Gene

Colon cancer is the third most common cancer type worldwide and is highly dependent on DNA mutations that progressively appear and accumulate in the normal colon epithelium. Mutations in the TP53 gene appear in approximately half of these patients and have significant implications in disease progression and response to therapy. miR-125b-5p is a controversial microRNA with a dual role in cancer that has been reported to target specifically TP53 in colon adenocarcinomas. Our study investigated the differential therapeutic effect of miR-125b-5p replacement in colon cancer based on the TP53 mutation status of colon cancer cell lines. In TP53 mutated models, miR-125b-5p overexpression slows cancer cells’ malignant behavior by inhibiting the invasion/migration and colony formation capacity via direct downregulation of mutated TP53. In TP53 wild type cells, the exogenous modulation of miR-125b-5p did not significantly affect the molecular and phenotypic profile. In conclusion, our data show that miR-125b-5p has an anti-cancer effect only in TP53 mutated colon cancer cells, explaining partially the dual behavior of this microRNA in malignant pathologies.
Association Between Gut Akkermansia and Metabolic Syndrome is Dose-Dependent and Affected by Microbial Interactions: A Cross-Sectional Study

Objective Akkermansia muciniphila is among the most abundant bacterial species in the human intestine; however, its relationship to metabolic syndrome (MetS)—which is linked to gut dysbiosis—is not known. In this study, we investigated the association between Akkermansia abundance and risk of MetS and its components, as well as dose–response effects and the influence of microbial interactions on the association. Methods This cross-sectional study included 6896 Chinese participants aged 18 to 97 years from the Guangdong Gut Microbiome Project. MetS was defined according to Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults criteria. The abundance of Akkermansia was assessed by 16S rRNA sequencing. Logistic regression analysis with adjustment for common confounders was performed to evaluate the association between Akkermansia and MetS and its components. Models with restricted cubic splines and interaction terms were used to examine the dose–response association and microbial interactions, respectively. Results The prevalence of MetS was 20.4%, and the median abundance of Akkermansia was 0.08% (interquartile range: 0.04–0.93%). Increased Akkermansia abundance was associated with decreased risk of MetS (Pnonlinear<0.05), but this effect was not observed until the Akkermansia level was 0.2% of the total gut microbiota abundance (odds ratio=0.96, 95% confidence interval: 0.94–0.98). Of the 5 MetS components, obesity and hypertriglyceridemia showed the strongest association with Akkermansia, followed by reduced high-density lipoprotein cholesterol, hypertension, and hyperglycemia. Microbial interaction analyses showed that Ruminococcaceae and Lachnospiraceae were the predominant bacterial families and were not only correlated with Akkermansia abundance but also influenced the Akkermansia–MetS association. Conclusion There is a dose–response association between reduced risk of MetS and increased abundance of Akkermansia. The association between Akkermansia and 5 MetS components is variable and affected by microbial interactions.
Respiratory Dysfunctions in Parkinson’s Disease Patients

Respiratory dysfunctions have been associated with Parkinson’s disease since the first observations of the disease in 1817. Patients with Parkinson’s disease frequently present respiratory disorders with obstructive ventilatory patterns and restrictive modifications, as well as limitations in respiratory volumes. In addition, respiratory impairments are observed due to the rigidity and kyphosis that Parkinson’s disease patients experience. Subsidiary pulmonary complications can also appear as side effects of medication. Silent aspiration can be the cause of pneumonia in Parkinson’s disease. Pulmonary dysfunction is one of the main factors that leads to the morbidity and mortality of patients with Parkinson’s disease. Here, we performed a narrative review of the literature and reviewed studies on dyspnea, lung volumes, respiratory muscle function, sleep breathing disorders, and subsidiary speech and swallow impairments related to pulmonary dysfunction in patients with Parkinson’s disease.
WHF Position Statement on COVID Vaccination

The current COVID-19 pandemic has challenged health systems and communities globally. As such, several countries have embarked on national COVID-19 vaccination programmes in order to curb spread of the disease. However, at present, there isn’t yet enough dosages to enable vaccination of the general population. Different vaccine prioritization strategies are thus being implemented in different communities in order to permit for a systematic vaccination of individuals. Here, on behalf of the World Heart Federation, we emphasize the need for individuals with Cardiovascular disease to be prioritized in national vaccine prioritization programmes as these are high risk individuals.
The Zebrafish Cardiac Endothelial Cell—Roles in Development and Regeneration

In zebrafish, the spatiotemporal development of the vascular system is well described due to its stereotypical nature. However, the cellular and molecular mechanisms orchestrating post-embryonic vascular development, the maintenance of vascular homeostasis, or how coronary vessels integrate into the growing heart are less well studied. In the context of cardiac regeneration, the central cellular mechanism by which the heart regenerates a fully functional myocardium relies on the proliferation of pre-existing cardiomyocytes; the epicardium and the endocardium are also known to play key roles in the regenerative process. Remarkably, revascularisation of the injured tissue occurs within a few hours after cardiac damage, thus generating a vascular network acting as a scaffold for the regenerating myocardium. The activation of the endocardium leads to the secretion of cytokines, further supporting the proliferation of the cardiomyocytes. Although epicardium, endocardium, and myocardium interact with each other to orchestrate heart development and regeneration, in this review, we focus on recent advances in the understanding of the development of the endocardium and the coronary vasculature in zebrafish as well as their pivotal roles in the heart regeneration process.
Effects of Starch Level and a Mixture of Sunflower and Fish Oils on Nutrient Intake and Digestibility, Rumen Fermentation, and Ruminal Methane Emissions in Dairy Cows

Simple Summary Methane produced by ruminants contributes to increased greenhouse gas effect. There are various nutritional strategies to reduce methane emission, such as supplementing fat or changing starch levels in the diet. Understanding the interactions of these strategies on methane emission, as well as performance, digestibility, and rumen fermentation is important. The present study aimed to assess the effects of starch level with or without a mixture of sunflower and fish oils on nutrient intake and digestibility, milk yield and composition, rumen fermentation, ruminal CH4 emissions and microbial ecology in dairy cows. Oil mixture rich in polyunsaturated fatty acids supplemented to low- or high-starch diets reduced dry matter intake and increased energy digestibility of lactating cows. High starch level improved nutrient digestibility and tended to reduce ruminal acetate:propionate ratio but did not affect rumen pH, molar propionate ratio, or ruminal CH4 emissions. Oil decreased absolute ruminal CH4 emission or tended to decrease CH4 per energy corrected milk. Abstract Four multiparous dairy cows were used in a 4 × 4 Latin square to examine how starch level and oil mixture impact dry matter (DM) intake and digestibility, milk yield and composition, rumen fermentation, ruminal methane (CH4) emissions, and microbial diversity. Experimental treatments comprised high (HS) or low (LS) levels of starch containing 0 or 30 g of a mixture of sunflower and fish oils (2:1 w/w) per kg diet DM (LSO and HSO, respectively). Intake of DM did not differ between cows fed LS and HS diets while oil supplementation reduced DM intake. Dietary treatments did not affect milk and energy corrected milk yields. There was a tendency to have a lower milk fat concentration due to HSO compared with other treatments. Both high starch level and oil supplementation increased digestibility of gross energy. Cows receiving HS diets had higher levels of total rumen VFA while acetate was lower than LS without any differences in rumen pH, or ruminal CH4 emissions. Although dietary oil supplementation had no impact on rumen fermentation, decreased CH4 emissions (g/day and g/kg milk) were observed with a concomitant increase in Anoplodinium-Diplodinium sp. and Epidinium sp. but a decrease in Christensenellaceae, Ruminococcus sp. , Methanobrevibacter ruminantium and Mbb. gottschalkii clades.
Association between Sugar Intake and Intima Media Thickness as a Marker for Atherosclerosis: A Cross-Sectional Study in the Malmö Diet and Cancer Study (Sweden)

It has been suggested that sugar intake may play a role in the development of atherosclerosis. However, studies on this matter are lacking. Intima media thickness (IMT) is a well-established measurement of subclinical atherosclerosis. This study aimed to investigate the cross-sectional association between sugar intake (i.e., added, free and total sugar and sugar-rich foods and beverages) and IMT. Our study comprised 5269 individuals (45–73 years, 40% men) of the Malmö Diet and Cancer Study, a population-based cohort conducted in Sweden with data collected from 1991 to 1994. Measurements of IMT were performed with B-mode ultrasound at the right common carotid artery (IMTcca) and the bifurcation of the carotids (IMTbif). Dietary intake was estimated using a combination of a 7-day food record, diet questionnaire and interview. After adjusting for methodological, lifestyle and dietary confounders, no statistically significant associations were observed for any of the sugar intake variables and IMT. For example, added sugar intake presented no significant linear association with IMTcca or IMTbif (Ptrends: IMTcca 0.81 for men and 0.98 for women and IMTbif 0.20 for men and 0.40 for women). In conclusion, we found no clear association between sugar intake and IMT measurements in this study.
The Evolution of Antisense Oligonucleotide Chemistry—A Personal Journey

Over the last four decades, tremendous progress has been made in use of synthetic oligonucleotides as therapeutics. This has been possible largely by introducing chemical modifications to provide drug like properties to oligonucleotides. In this article I have summarized twists and turns on use of chemical modifications and their road to success and highlight areas of future directions.
Effects of Respiratory Muscle Training on Baroreflex Sensitivity, Respiratory Function, and Serum Oxidative Stress in Acute Cervical Spinal Cord Injury

Background: respiratory complications are a leading cause of morbidity and mortality in individuals with spinal cord injury (SCI). We examined the effects of respiratory muscle training (RMT) in patients with acute cervical SCI. Methods: this prospective trial enrolled 44 adults with acute cervical SCI, of which twenty received RMT and twenty-four did not receive RMT. Respiratory function, cardiovascular autonomic function, and reactive oxidative species (ROS) were compared. The experimental group received 40-min high-intensity home-based RMT 7 days per week for 10 weeks. The control group received a sham intervention for a similar period. The primary outcomes were the effects of RMT on pulmonary and cardiovascular autonomic function, and ROS production in individuals with acute cervical SCI. Results: significant differences between the two groups in cardiovascular autonomic function and the heart rate response to deep breathing (p = 0.017) were found at the 6-month follow-up. After RMT, the maximal inspiratory pressure (p = 0.042) and thiobarbituric acid-reactive substances (TBARS) (p = 0.006) improved significantly, while there was no significant difference in the maximal expiratory pressure. Significant differences between the two groups in tidal volume (p = 0.005) and the rapid shallow breathing index (p = 0.031) were found at 6 months. Notably, the SF-36 (both the physical (PCS) and mental (MCS) component summaries) in the RMT group had decreased significantly at the 6-month follow-up, whereas the clinical scores did not differ significantly (p = 0.333) after RMT therapy. Conclusions: High-intensity home-based RMT can improve pulmonary function and endurance and reduce breathing difficulties in patients with respiratory muscle weakness after injury. It is recommended for rehabilitation after spinal cord injury.
Graphene Formation through Pulsed Wire Discharge of Graphite Strips in Water: Exfoliation Mechanism

This study aims to clarify the mechanism of exfoliation of graphene through electrical pulsed wire discharge (PWD) of a graphite strip, made by the compression of inexpensive expanded graphite in water. The explosion of the graphite strip was visualized using a high-speed video camera. During the energized heating of the sample, explosions, accompanied by shock waves due to expansion of gas inside the sample, occurred at various locations of the sample, and the sample started to expand rapidly. The exfoliated graphene was observed as a region with low light transmittance. The PWD phenomenon of graphite strips, a type of porous material, is reasonably explained by the change in electrical resistivity of the sample during discharge and the light emission due to energy transition of the excited gas.
Investigating the Circulation of Ebola Viruses in Bats during the Ebola Virus Disease Outbreaks in the Equateur and North Kivu Provinces of the Democratic Republic of Congo from 2018

With 12 of the 31 outbreaks, the Democratic Republic of Congo (DRC) is highly affected by Ebolavirus disease (EVD). To better understand the role of bats in the ecology of Ebola viruses, we conducted surveys in bats during two recent EVD outbreaks and in two areas with previous outbreaks. Dried blood spots were tested for antibodies to ebolaviruses and oral and rectal swabs were screened for the presence of filovirus using a broadly reactive semi-nested RT-PCR. Between 2018 and 2020, 892 (88.6%) frugivorous and 115 (11.4%) insectivorous bats were collected. Overall, 11/925 (1.2%) to 100/925 (10.8%) bats showed antibodies to at least one Ebolavirus antigen depending on the positivity criteria. Antibodies were detected in fruit bats from the four sites and from species previously documented to harbor Ebola antibodies or RNA. We tested for the first time a large number of bats during ongoing EVD outbreaks in DRC, but no viral RNA was detected in the 676 sampled bats. Our study illustrates the difficulty to document the role of bats as a source of Ebolaviruses as they might clear quickly the virus. Given the increasing frequency of EVD outbreaks, more studies on the animal reservoir are urgently needed.
A Skin Cancer Prophylaxis Study in Hairless Mice Using Methylene Blue, Riboflavin, and Methyl Aminolevulinate as Photosensitizing Agents in Photodynamic Therapy

The high incidence of sunlight-induced human skin cancers reveals a need for more effective photosensitizing agents. In this study, we compared the efficacy of prophylactic photodynamic therapy (PDT) when methylene blue (MB), riboflavin (RF), or methyl aminolevulinate (MAL) were used as photosensitizers. All mice in four groups of female C3.Cg/TifBomTac hairless immunocompetent mice (N = 100) were irradiated with three standard erythema doses of solar-simulated ultraviolet radiation (UVR) thrice weekly. Three groups received 2 × 2 prophylactic PDT treatments (days 45 + 52 and 90 + 97). The PDT treatments consisted of topical administration of 16% MAL, 20% MB, or 20% RF, and subsequent illumination that matched the photosensitizers’ absorption spectra. Control mice received no PDT. We recorded when the first, second, and third skin tumors developed. The pattern of tumor development after MB-PDT or RF-PDT was similar to that observed in irradiated control mice (p > 0.05). However, the median times until the first, second, and third skin tumors developed in mice given MAL-PDT were significantly delayed, compared with control mice (256, 265, and 272 vs. 215, 222, and 230 days, respectively; p < 0.001). Only MAL-PDT was an effective prophylactic treatment against UVR-induced skin tumors in hairless mice.
Breath-Triggered Drug Release System for Preterm Neonates

A major disadvantage of inhalation therapy with continuous drug delivery is the loss of medication during expiration. Developing a breath-triggered drug release system can highly decrease this loss. However, there is currently no breath-triggered drug release directly inside the patient interface (nasal prong) for preterm neonates available due to their high breathing frequency, short inspiration time and low tidal volume. Therefore, a nasal prong with an integrated valve releasing aerosol directly inside the patient interface increasing inhaled aerosol efficiency is desirable. We integrated a miniaturized aerosol valve into a nasal prong, controlled by a double-stroke cylinder. Breathing was simulated using a test lung for preterm neonates on CPAP respiratory support. The inhalation flow served as a trigger signal for the valve, releasing humidified surfactant. Particle detection was performed gravimetrically (filter) and optically (light extinction). The integrated miniaturized aerosol valve enabled breath-triggered drug release inside the patient interface with an aerosol valve response time of <25 ms. By breath-triggered release of the pharmaceutical aerosol as a bolus during inhalation, the inhaled aerosol efficiency was increased by a factor of >4 compared to non-triggered release. This novel nasal prong with integrated valve allows breath-triggered drug release directly inside the nasal prong with short response time.