Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis.

Histone acetylation plays critical roles in chromatin remodeling, DNA repair, and epigenetic regulation of gene expression, but the underlying mechanisms are unclear. Proteasomes usually catalyze ATP- and polyubiquitin-dependent proteolysis. Here, we show that the proteasomes containing the activator PA200 catalyze the polyubiquitin-independent degradation of histones. Most proteasomes in mammalian testes ("spermatoproteasomes") contain a spermatid/sperm-specific α subunit α4 s/PSMA8 and/or the catalytic ß subunits of immunoproteasomes in addition to PA200. Deletion of PA200 in mice abolishes acetylation-dependent degradation of somatic core histones during DNA double-strand breaks and delays core histone disappearance in elongated spermatids. Purified PA200 greatly promotes ATP-independent proteasomal degradation of the acetylated core histones, but not polyubiquitinated proteins. Furthermore, acetylation on histones is required for their binding to the bromodomain-like regions in PA200 and its yeast ortholog, Blm10. Thus, PA200/Blm10 specifically targets the core histones for acetylation-mediated degradation by proteasomes, providing mechanisms by which acetylation regulates histone degradation, DNA repair, and spermatogenesis.

Altered microbiome of serum exosomes in patients with acute and chronic cholecystitis.

BACKGROUND: This study aimed to investigate the differences in the microbiota composition of serum exosomes from patients with acute and chronic cholecystitis. METHOD: Exosomes were isolated from the serum of cholecystitis patients through centrifugation and identified and characterized using transmission electron microscopy and nano-flow cytometry. Microbiota analysis was performed using 16S rRNA sequencing. RESULTS: Compared to patients with chronic cholecystitis, those with acute cholecystitis exhibited lower richness and diversity. Beta diversity analysis revealed significant differences in the microbiota composition between patients with acute and chronic cholecystitis. The relative abundance of Proteobacteria was significantly higher in exosomes from patients with acute cholecystitis, whereas Actinobacteria, Bacteroidetes, and Firmicutes were significantly more abundant in exosomes from patients with chronic cholecystitis. Furthermore, functional predictions of microbial communities using Tax4Fun analysis revealed significant differences in metabolic pathways such as amino acid metabolism, carbohydrate metabolism, and membrane transport between the two patient groups. CONCLUSIONS: This study confirmed the differences in the microbiota composition within serum exosomes of patients with acute and chronic cholecystitis. Serum exosomes could serve as diagnostic indicators for distinguishing acute and chronic cholecystitis.

Impact of travel ban implementation on COVID-19 spread in Singapore, Taiwan, Hong Kong and South Korea during the early phase of the pandemic: a comparative study.

BACKGROUND: The COVID-19 pandemic has elicited imposition of some form of travel restrictions by almost all countries in the world. Most restrictions currently persist, although some have been gradually eased. It remains unclear if the trade-off from the unprecedented disruption to air travel was well worth for pandemic containment. METHOD: A comparative analysis was conducted on Singapore, Taiwan, Hong Kong and South Korea's COVID-19 response. Data on COVID-19 cases, travel-related and community interventions, socio-economic profile were consolidated. Trends on imported and local cases were analyzed using computations of moving averages, rate of change, particularly in response to distinct waves of travel-related interventions due to the outbreak in China, South Korea, Iran & Italy, and Europe. RESULTS: South Korea's travel restrictions were observed to be consistently more lagged in terms of timeliness and magnitude, with their first wave of travel restrictions on flights departing from China implemented 34 days after the outbreak in Wuhan, compared to 22-26 days taken by Singapore, Taiwan and Hong Kong. South Korea's restrictions against all countries came after 91 days, compared to 78-80 days for the other three countries. The rate of change of imported cases fell by 1.08-1.43 across all four countries following the first wave of travel restrictions on departures from China, and by 0.22-0.52 in all countries except South Korea in the fifth wave against all international travellers. Delayed rate of change of local cases resulting from travel restrictions imposed by the four countries with intrinsic importation risk, were not observed. CONCLUSIONS: Travel restriction was effective in preventing COVID-19 case importation in early outbreak phase, but may still be limited in preventing general local transmission. The impact of travel restrictions, regardless of promptness, in containing epidemics likely also depends on the effectiveness of local surveillance and non-pharmaceutical interventions concurrently implemented.

Association between micronutrient deficiency and acute respiratory infections in healthy adults: a systematic review of observational studies.

BACKGROUND: Acute respiratory infections (ARI), including the common cold causes significant morbidity and economical losses globally. Micronutrient deficiency may increase ARI incidence risk and its associated duration and severity among healthy adults, but evidence are inconclusive. This study aims to systematically review all observations on the association between single micronutrient deficiency and ARI incidence, duration and severity in healthy adults. METHODS: Systematic literature searches were conducted in PubMed, Cochrane Library, Embase and Scopus databases. Eligible studies were assessed for the reporting and methodological quality. Adjusted summary statistics with their relevant 95% confidence intervals or interquartile ranges were extracted for the outcomes of interest. RESULTS: The literature search identified 423 unique studies. Of which, only eight studies were eligible and included in the final review. Only vitamin D deficiency (VDD) was observed among these eight studies. There were no eligible studies that focused on the association between other single micronutrient deficiency and ARI. The review found mixed observations on ARI incidence, and a lack of evidence on its associated severity to conclude the association between VDD and these outcomes. However, existing evidence consistently suggested that VDD is likely to lead to longer ARI duration (median duration in days: deficient group, 4 to 13; non-deficient groups, 2 to 8). CONCLUSION: This review found that VDD may be associated to longer ARI duration, but its effect on ARI incidence and its associated severity among healthy adults remains inconclusive. This review also highlighted the lack of a consistent regional and/or global definition for micronutrient sufficiency, and that future studies should explore and conclude the association between other micronutrient deficiency and ARIs in healthy adults before considering supplementation for ARI prevention and management.

[Application prospect of new technology and new equipment in production of Chinese patent medicine].

At present,the production equipment and process of Chinese patent medicines still have many problems including high energy consumption,low efficiency,high pollution,and low intelligence,which seriously hinder the transformation,upgrading and modernized development of traditional Chinese medicine industry. With the emergence of various new pharmaceutical technologies and the application of technologies of other fields in traditional Chinese medicine industry,the development of Chinese patent medicine has ushered in new opportunities. The processes such as pulverization,mixing,extraction,separation,concentration,drying and sterilization are unique for the production of Chinese patent medicine. These main features can be distinguished from the manufacturing process of chemical drugs,determining the characteristics of the production process and equipment of Chinese patent medicine. In this paper,each operation unit was mentioned to summarize and analyze the new equipment and new technologies with advantages and characteristics in recent years from the perspectives of definition,principle,classification and application. Among them,the automatic spray device of the mixer,the extraction and separation equipment of volatile oil,and the crane basket-type circulation extraction technology,composite multi-layer spiral vibration countercurrent drying,and vibration sterilization equipment all have rapid development in recent years,with great prospects in the production of Chinese patent medicines. In this paper,we also analyzed some problems existing in the production equipment and technology of Chinese patent medicine and the key factors restricting the development of Chinese patent medicine,discussed the transformation of Chinese patent medicine production from traditional to modern and from semi-automatic to intelligent,and put forward three suggestions to help Chinese patent medicine achieve the goal of improving quality,efficiency and green manufacturing in production.

Electrical performance and scalability of Pt dispersed SiO2 nanometallic resistance switch.

Highly reproducible bipolar resistance switching was recently demonstrated in a composite material of Pt nanoparticles dispersed in silicon dioxide. Here, we examine the electrical performance and scalability of this system and demonstrate devices with ultrafast (<100 ps) switching, long state retention (no measurable relaxation after 6 months), and high endurance (>3 × 10(7) cycles). A possible switching mechanism based on ion motion in the film is discussed based on these observations.

Transfusion of Blood Products and Clinical Outcomes for Patients With Dengue Fever: A Systematic Review and Meta-analysis.

Background: This systematic review and meta-analysis aimed to analyze the effects of transfusing "nonpacked red blood cell" blood products in patients with dengue and evaluate the effectiveness in reducing mean hospital stay, bleeding, mortality rate, and intensive care unit requirements. Methods: Four databases were searched for relevant articles. Inclusion criteria were prospective or retrospective randomized or nonrandomized studies investigating the effects of transfusion of blood products in patients with dengue. Results: Nine studies were included in the final meta-analysis. Transfusion of blood products was associated with significantly higher mortality rate (9 studies; odds ratio [OR], 3.59 [95% confidence interval [CI], 1.07-15.98]; I 2 = 0%; P = .04) and significantly longer mean hospital stay (6 studies; 0.56 day [95% CI, .03-1.08 day]; I 2 = 95%; P = .04). There was no significant difference in the incidence of clinical bleeding (7 studies; OR, 1.13 [95% CI, .77-1.65]; I 2 = 39%; P = .54) or intensive care unit requirement (3 studies; OR, 1.59 [.40-6.39]; I 2 = 0%; P = .51). Conclusions: Transfusing blood products for patients with dengue showed no benefit and may even be harmful.

Caulerprenylols A and B, two rare antifungal prenylated para-xylenes from the green alga Caulerpa racemosa.

Two new prenylated para-xylenes, named caulerprenylols A (1) and B (2), were isolated from the green alga Caulerpa racemosa, collected from the Zhanjiang coastline, China. The structures of the two metabolites were elucidated on the basis of detailed spectroscopic analysis. This is the first report of prenylated para-xylenes from marine algae and from marine organisms as well. Moreover, caulerprenylol B (2) is also characterized by an uncommon indane ring system. In in vitro bioassays, the new compounds exhibited a broad spectrum of antifungal activity against Candida glabrata (537), Trichophyton rubrum (Cmccftla), and Cryptococcus neoformans (32609) with MIC80 values between 4 and 64 µg/mL when compared to amphotericin B (MIC80 values of 2.0, 1.0, and 4.0 µg/mL, respectively) as a positive control and showed no growth inhibition activity against the tumor cells HL60 and A549.

[Effect of litchi seed aqueous extracts on learning and memory obstacles induced by D-galactose in mice and its mechanism].

OBJECTIVE: To investigate the improving effect of Litchi Seed Aqueous Extracts on learning and memory obstacles model and its mechanism. METHODS: The learning and memory obstacles model was incluced by subcutoneous injection of D-galactose (500 mg/kg) for 8 weeks. The model group and treatment groups were given huperzine A (0.4 mg/kg) and Litchi Seed Aqueous Extracts (15,60 g/kg) respectively for 4 weeks by ig at the 5th week. After huperzine A and Litchi Seed Aqueous Extracts treatment for 4 weeks, water maze test was used to determine the ability of mice's spatial learning and memory. The contents of advanced glycation end products (AGEs) in serum, the content of nitric oxide (NO) and acetylcholine (Ach), the activity of nitric oxide synthase (NOS) and acetylcholinesterase (AchE) in the brain tissue were detected. RESULTS: Litchi Seed Aqueous Extracts significantly ameliorated the learning and memory ability in mice, decreased the level of AGEs in serum, and reduced the content of NO and activity of NOS in brain tissues. No significantly influence was observed for the Ach and Ach-E in brain tissues. CONCLUSION: Litchi Seed Aqueous Extracts possesses improving the learning and memory effects on the model mice induced by D-galactose, which may be related to inhibiting too much AGEs and NO formation and reducing damage in the brain cells.

The knowledge, attitudes and practices of hand, foot, and mouth disease prevention strategies amongst parents and educators of children under 5 years amidst COVID-19 pandemic: A cross-sectional study.

Background: Hand, foot, and mouth disease (HFMD) is endemic in Singapore. Prevention efforts have been ramped up since major outbreaks in the early 2000's. This study aims to assess the current knowledge, and attitudes towards and practise (KAP) levels of HFMD prevention strategies (HFMD-PS) amongst parents and teachers of children under 5 years amidst the COVID-19 pandemic. Methods and results: A convenience sample of 240 teachers and 404 parents responded to a self-administered standardised questionnaire between mid-October and December 2020. A scoring framework was used to assess responses in the 'knowledge', 'attitude', and 'practice' domains. A multivariable analysis was adjusted for ethnicity and attitudes towards getting children to follow proper handwashing steps and regularly disinfecting children's toys amongst parents, knowledge about HFMD's infectious period, and the responses to a child turning symptomatic in the childcare centre amongst teachers. Existing levels of knowledge and attitudes of parents and teachers were not high, and only a small proportion practised high levels of prevention measures (99 parents and 28 teachers). Key facilitators for a higher practise level in parents include the following: (1) awareness of regular liquid soap's efficacy as a disinfectant, (2) toy cleaning before and after playtime, and (3) the cleaning agent used for this practise. Teachers had no significant factors associated with higher practise levels. Conclusion: This study suggested potential gaps between positive knowledge and attitudes towards prevention strategies and their actual adoption levels in homes and childcare centres during COVID-19 pandemic. These evidences suggest the importance of continuous promotion of HFMD prevention practise in homes and childcare centres, even amidst pandemics.