Previous studies on informational cascades have stressed the importance of informational social influences in decision-making. When people use the product evaluations of others to indicate product ...quality on the Internet, online herd behavior occurs. This work presents four studies examining herd behavior of online book purchasing. The first two studies addressed how two cues frequently found on the Internet, i.e., star ratings and sales volume, influence consumer online product choices. The last two studies investigated the relative effectiveness of different recommendation sources. The experimental results demonstrated that subjects use the product evaluations and choices of others as cues in making purchasing book decisions on the Internet bookstore. Additionally, recommendations of other consumers exerted a greater influence on subject choices than recommendations of an expert. Finally, recommendations from recommender system influenced online consumer choices more than those from website owners. The results and implications of this research are discussed.
With-no-lysine (WNK) kinases regulate renal sodium-chloride cotransporter (NCC) to maintain body sodium and potassium homeostasis. Gain-of-function mutations of WNK1 and WNK4 in humans lead to a ...Mendelian hypertensive and hyperkalemic disease pseudohypoaldosteronism type II (PHAII). X-ray crystal structure and in vitro studies reveal chloride ion (Cl⁻) binds to a hydrophobic pocket within the kinase domain of WNKs to inhibit its activity. The mechanism is thought to be important for physiological regulation of NCC by extracellular potassium. To test the hypothesis that WNK4 senses the intracellular concentration of Cl⁻ physiologically, we generated knockin mice carrying Cl⁻-insensitive mutant WNK4. These mice displayed hypertension, hyperkalemia, hyperactive NCC, and other features fully recapitulating human and mouse models of PHAII caused by gain-of-function WNK4. Lowering plasma potassium levels by dietary potassium restriction increased NCC activity in wild-type, but not in knockin, mice. NCC activity in knockin mice can be further enhanced by the administration of norepinephrine, a known activator of NCC. Raising plasma potassium by oral gavage of potassium inactivated NCC within 1 hour in wild-type mice, but had no effect in knockin mice. The results provide compelling support for the notion that WNK4 is a bona fide physiological intracellular Cl⁻ sensor and that Cl⁻ regulation of WNK4 underlies the mechanism of regulation of NCC by extracellular potassium.
Scope
The consumption of artificial sweeteners has been rapidly increasing, with potentially hazardous effects on human reproduction. This study aims to explore the effect of Acesulfame Potassium ...(Ace K) and its potential mechanism to induce uterine contraction through in vitro, ex vivo, in vivo, and clinical observation studies.
Methods and results
Used ex vivo and in vitro studies to analyze its effect on uterine contraction and involved signaling pathway. Used the long‐term, high‐dose exposure to examine Ace K's affection for contractive‐related protein expression. By involving a cohort of 613 participants, to assess the dose‐responsiveness of Ace K consumption and calculate the odd ratio of Ace K consumption and the relationship with preterm risk. Animal studies show increasing uterine contraction, cytokine secretion, and altered contraction‐related protein expression. Human data show that higher consumption of Ace K may be related to early delivery.
Conclusion
Long‐term high‐dose exposure to Ace K can induce uterine hypercontraction, increase cytokine secretion, and alters contraction‐related protein expression. These findings suggest that women who suffer from uterine hypercontraction causes painfulness should pay more attention to the zero‐ or low‐calorie soft drinks or food products containing Ace K.
The consumption of Ace K can increase the risk of hyper‐uterine contraction by increasing calcium influx through JNK‐related signaling transduction. Long‐term high‐dose exposure to Ace K can increases the oxidative stress, inflammatory cytokine secretion, and alter contraction‐related protein expression. These findings suggest that women who suffer from the uterine hypercontraction causes painfulness should pay more attention to the zero‐ or low‐calorie soft drinks or food products containing Ace K.
The emergence of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) variants has altered the trajectory of the COVID‐19 pandemic and raised some uncertainty on the long‐term efficiency of ...vaccine strategy. The development of new therapeutics against a wide range of SARS‐CoV‐2 variants is imperative. We, here, have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS‐CoV‐2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma, and Epsilon, at picomolar ranges of IC50 in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by cotreatment in K18‐hACE2‐transgenic mice, accompanied by a significant prevention of virus‐associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggest that C6G25S provides an alternative and effective approach to combating the COVID‐19 pandemic.
Synopsis
C6G25S is a fully modified siRNA specifically targeting the highly‐conserve region of SARS‐CoV‐2 genome. It has been developed as an inhalable and broad‐spectrum therapeutic that is highly stable and effective via direct respiratory administration.
A broadly active siRNA covers 99.8% of SARS‐CoV‐2 variants, including highly infective Delta and Omicron.
C6G25S completely inhibited the Delta variant in lungs of infected mice by prophylactic treatment and decreased 93% of virions by co‐treatment.
First study that use fully modified siRNA for inhalation and achieved promising therapeutic effect without a special delivery system.
C6G25S is a safe, effective, and feasible therapeutic approach that could reach the market in a short time.
C6G25S is a fully modified siRNA specifically targeting the highly‐conserve region of SARS‐CoV‐2 genome. It has been developed as an inhalable and broad‐spectrum therapeutic that is highly stable and effective via direct respiratory administration.
Racial disparities exist in outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
To evaluate the contribution of race/ethnicity in SARS-CoV-2 testing, infection, and ...outcomes.
Retrospective cohort study (1 February 2020 to 31 May 2020).
Integrated health care delivery system in Northern California.
Adult health plan members.
Age, sex, neighborhood deprivation index, comorbid conditions, acute physiology indices, and race/ethnicity; SARS-CoV-2 testing and incidence of positive test results; and hospitalization, illness severity, and mortality.
Among 3 481 716 eligible members, 42.0% were White, 6.4% African American, 19.9% Hispanic, and 18.6% Asian; 13.0% were of other or unknown race. Of eligible members, 91 212 (2.6%) were tested for SARS-CoV-2 infection and 3686 had positive results (overall incidence, 105.9 per 100 000 persons; by racial group, White, 55.1; African American, 123.1; Hispanic, 219.6; Asian, 111.7; other/unknown, 79.3). African American persons had the highest unadjusted testing and mortality rates, White persons had the lowest testing rates, and those with other or unknown race had the lowest mortality rates. Compared with White persons, adjusted testing rates among non-White persons were marginally higher, but infection rates were significantly higher; adjusted odds ratios aORs for African American persons, Hispanic persons, Asian persons, and persons of other/unknown race were 2.01 (95% CI, 1.75 to 2.31), 3.93 (CI, 3.59 to 4.30), 2.19 (CI, 1.98 to 2.42), and 1.57 (CI, 1.38 to 1.78), respectively. Geographic analyses showed that infections clustered in areas with higher proportions of non-White persons. Compared with White persons, adjusted hospitalization rates for African American persons, Hispanic persons, Asian persons, and persons of other/unknown race were 1.47 (CI, 1.03 to 2.09), 1.42 (CI, 1.11 to 1.82), 1.47 (CI, 1.13 to 1.92), and 1.03 (CI, 0.72 to 1.46), respectively. Adjusted analyses showed no racial differences in inpatient mortality or total mortality during the study period. For testing, comorbid conditions made the greatest relative contribution to model explanatory power (77.9%); race only accounted for 8.1%. Likelihood of infection was largely due to race (80.3%). For other outcomes, age was most important; race only contributed 4.5% for hospitalization, 12.8% for admission illness severity, 2.3% for in-hospital death, and 0.4% for any death.
The study involved an insured population in a highly integrated health system.
Race was the most important predictor of SARS-CoV-2 infection. After infection, race was associated with increased hospitalization risk but not mortality.
The Permanente Medical Group, Inc.
Background
Probiotics may alter the gut microbiota and may reduce antibiotic‐related dysbiosis after H. pylori eradication. However, whether probiotics are effective in reducing the bacterial load of ...H. pylori and modifying the gut microbiota remains unknown. We aimed to assess the efficacy of Lactobacillus acidophilus and Lactobacillus rhamnosus in reducing the bacterial load of H. pylori and modifying the gut microbiota.
Materials and methods
In this double‐blind, randomized, placebo‐controlled trial, we recruited 40 adult subjects with moderate to high bacterial loads of H. pylori, defined as a mean delta over baseline (DOB) value of the 13C‐urea breath test (13C‐UBT) of 10 or greater every 4 days 6 times. Eligible subjects were randomized in a 1:1 ratio to receive either probiotics containing Lactobacillus acidophilus and Lactobacillus rhamnosus or placebo twice daily for 4 weeks. 13C‐UBT was measured weekly from the beginning of treatment to 2 weeks after treatment. Amplification of the V3 and V4 hypervariable regions of the 16S rRNA was performed for fecal microbiota.
Results
A total of 40 subjects were randomized to receive probiotics or placebo. The DOB value was significantly lower in the probiotic group than in the placebo group after 4 weeks of treatment (26.0 vs. 18.5, p = .045). The DOB value was significantly reduced compared to that at baseline in the probiotic group (18.5 vs. 26.7, p = .001) but not in the placebo group (26.0 vs. 25.0, p = .648). However, the eradication rate for H. pylori was 0% in both groups. There was no significant difference in the DOB values between the two groups 1 and 2 weeks after discontinuation of the probiotics. There were also no significant changes observed in the α‐diversity and β‐diversity at week 4 compared to baseline in the probiotic group (p = .77 and 0.91) and the placebo group (p = .26 and 0.67).
Conclusions
Although the use of Lactobacillus acidophilus and Lactobacillus rhamnosus may reduce the bacterial load of H. pylori, there were no significant changes in the composition of gut microbiota. This trial is registered with ClinicalTrials.gov, NCT02725138.
Trehalose synthase converts maltose into trehalose in a single conversion step via intramolecular transformation and is thus useful for industrial production. In this study, we synthesized a ...thermophilic trehalose synthase from Thermus antranikianii (TaTS), which was recombinantly expressed in Escherichia coli BL21(DE3). The recombinant TaTS showed the highest activity at pH 7.0 and 60°C, with the maximum trehalose yield (76.8%) obtained at pH 7.0 and 30°C. TaTS activity was stable over a wide pH and temperature range of 6–10 and 4–70°C, respectively, over 6 h of incubation. The enzyme activity was strongly inhibited by Co2+, Cu2+, Zn2+, sodium dodecyl sulfate, and Tris. TaTS showed a 1.48-fold higher catalytic efficiency (kcat/Km) for maltose than for trehalose. Overall, these results demonstrate the good application potential of the recombinant enzyme TaTS in the efficient conversion of trehalose from maltose, with superior environmental tolerance to other trehalose synthases reported.
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•Thermophilic trehalose synthase from Thermus antranikianii (TaTS) was obtained.•Recombinant TaTS was expressed in Escherichia coli BL21(DE3).•TaTS showed high pH (pH 6–10) and temperature (4–70°C) resistance.•Maximum trehalose conversion yield (76.8%) of TaTS occurred at pH 7.0 and 30°C.•TaTS shows good potential for large-scale industrial production of trehalose.
Energy status and respiration metabolism of “Fuyan” longan fruit treated by hydrogen peroxide (H2O2) and their relationship to pericarp browning were studied. The results displayed that H2O2 ...significantly increased the respiration rate, increased activities of respiratory terminal oxidases like cytochrome C oxidase (CCO) and ascorbic acid oxidase (AAO), decreased NAD kinase activity, maintained lower contents of NADP and NADPH as well as higher amounts of NAD and NADH, and accelerated the decrease of energy charge. These results gave convincing evidence that the treatment of H2O2 for accelerating longan pericarp browning was due to an increase of energy deficiency, an increase of respiratory metabolic pathways of Embden–Meyerhof pathway (EMP) and tricarboxylic acid (TCA) cycle, a decrease of pentose phosphate pathway (PPP) of respiratory pathway, and an increase of activities of respiratory terminal oxidases like CCO and AAO.
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects women of reproductive age, characterized by androgen-induced oxidative stress leading to several metabolic disorders. In ...this study, we investigated the potential therapeutic effect of caffeic acid on PCOS and its underlying molecular mechanism. We used a human ovarian granulosa cell line (KGN cells) induced by hydrogen peroxide (H2O2) to examine how caffeic acid influences the protein expression of oxidative stress-induced apoptosis-related markers. Our results indicate that caffeic acid significantly inhibits intracellular reactive oxygen species (ROS) generation and safeguards KGN cells against oxidative stress. For the in vivo aspect of our study, female Sprague-Dawley (SD) rats were utilized to induce the PCOS model using dehydroepiandrosterone (DHEA). Caffeic acid was then administered to the rats for a duration of 6 weeks. The outcomes revealed that caffeic acid effectively improved irregular estrous cycles, fasting blood glucose levels, liver function, and lipid profiles in DHEA-induced PCOS rats. Additionally, it mitigated hyperandrogenism, enhanced steroidogenesis enzyme expression, and modulated apoptosis-related protein expression. Our findings strongly suggest that caffeic acid holds promising potential in reducing oxidative stress-induced damage and ameliorating PCOS-related complications by modulating ER stress.
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•Caffeic acid possesses antioxidant properties that can protect KGN cells from H2O2-mediated oxidative stress and cell apoptosis-related protein expression.•Caffeic acid can improve DHEA-induced estrous cycle disorders, fasting blood glucose levels, lipid profiles, liver function, and oxidative stress.•The reduction of excessive androgen levels and improve the expression of steroidogenesis enzymes, ER stress and apoptosis-related protein expression in PCOS rats.
Erythropoietin (EPO) is a circulating hormone conventionally considered to be responsible for erythropoiesis. In addition to facilitating red blood cell production, EPO has pluripotent potential, ...such as for cognition improvement, neurogenesis, and anti-fibrotic, anti-apoptotic, anti-oxidative, and anti-inflammatory effects. In human retinal tissues, EPO receptors (EPORs) are expressed in the photoreceptor cells, retinal pigment epithelium, and retinal ganglion cell layer. Studies have suggested its potential therapeutic effects in many neurodegenerative diseases, including glaucoma. In this review, we discuss the correlation between glaucoma and EPO, physiology and potential neuroprotective function of the EPO/EPOR system, and latest evidence for the treatment of glaucoma with EPO.
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