HDAC6-dependent deacetylation of AKAP12 dictates its ubiquitination and promotes colon cancer metastasis.

Aberrant expression of histone deacetylase 6 (HDAC6) is greatly involved in neoplasm metastasis, which is a leading cause of colon cancer related death. Thus, deep understanding of the regulatory mechanisms of HDAC6 in the metastasis of colon cancer is warranted. In this study, we firstly found that HDAC6 expression was highly expressed in metastatic colon cancer tissues and inhibition or knockdown of HDAC6 suppressed colon cancer metastasis. Next, based on proteomic analysis we uncovered A-kinase anchoring protein 12 (AKAP12) was a novel substrate of HDAC6. HDAC6 interacted with AKAP12 and deacetylated the K526/K531 residues of AKAP12. Moreover, deacetylation of AKAP12 at K531 by HDAC6 increased its ubiquitination level, which facilitated AKAP12 proteasome-dependent degradation. Importantly, we observed an inverse correlation between AKAP12 and HDAC6 protein levels with human colon cancer specimens. Further deletion of AKAP12 in HDAC6 knockdown cells restored the cell motility defects and reactivated the protein kinase C isoforms, repression of which were responsible for the inhibition of cancer metastasis of AKAP12. Our study identified AKAP12 was a new interactor and substrate of HDAC6 and uncovered a novel mechanism through which HDAC6-dependent AKAP12 deacetylation led to its ubiquitination mediated degradation and promoted colon cancer metastasis.

Tai Chi for Overweight/Obese Adolescents and Young Women with Polycystic Ovary Syndrome: A Randomized Controlled Pilot Trial.

Background: Exercise is one of the recommended interventions for polycystic ovary syndrome (PCOS), and current evidence has shown that Tai chi may have favorable effects. The objective of this randomized controlled pilot trial was to study the feasibility and potential effects of Tai chi for overweight/obese adolescents and young women with PCOS, so a future definitive randomized controlled trial (RCT) can be well designed and implemented. Materials and Methods: This study recruited 50 patients who were randomly assigned to two groups (Tai chi and self-monitored exercise) at a ratio of 3 : 2. The intervention lasted for 3 months, and the feasibility and effectiveness outcomes were measured. Results: A total of 42 patients completed the study, including 24 in the Tai chi group and 18 in the control group. Compared with the self-monitored exercise group, there was a significantly decreased body mass index (BMI) in the Tai chi group adjusted for baseline BMI. The testosterone level and lipid profile were also decreased compared to controls; the same tendency was also observed for the homeostasis model assessment of insulin resistance (HOMA-IR), but the difference did not achieve statistical significance. Twenty-four (out of 30, 80%) patients in the Tai chi group and 18 (out of 20, 90%) patients in the self-monitored exercise group completed the data collection. A total of 36 exercise sessions were held in both groups. Patients in the Tai chi group took a mean of 34.0 ± 2.21 classes (93.06%), and those in the self-monitored exercise group engaged in 32 ± 3.06 exercise sessions (88.27%) out of the 36 required exercise sessions. Conclusions: The present pilot study was feasible to deliver; there was a decrease in BMI, testosterone level, and lipid profile for PCOS patients in the Tai chi group at 3 months. In a future definitive trial, lower recruitment rate and outcome measurements lead to poor patient acceptance such as the 5-time point oral glucose tolerance test need to be considered and one fixed type of aerobic exercise and supervision from the investigator for the control group are also needed. Trial registration: ClinicalTrials.gov, NCT02608554.

Evaluation of effectiveness, safety and cost-benefit of the 23- valent pneumococcal capsular polysaccharide vaccine for HIV-Infected patients.

INTRODUCTION: Due to the lack of understanding of the protective effects and safety of 23-valent pneumococcal polysaccharide vaccine (PPV23) in immune-deficient populations, the vaccination rate of PPV23 among HIV-infected patients is still very low in China. The main objectives of this study were to determine whether the efforts to assess measures for the prevention of pneumococcal pneumonia are still worthwhile, and provide designated vaccination program of HIV-infected persons for government policy based on. METHODS: 60 HIV-infected adults in Lanshan county who had never been vaccinated with any pneumococcal vaccine were enrolled in this study, voluntary vaccination of PPV23 and One-year follow-up after vaccination can be completed. RESULT: 76.67% patients (46/60) had serologic response at 12 months after vaccine, CD4 count(≤500 cells/ul or > 500 cells/ul) and Month from diagnosis to first antiviral therapy (≤1 month or > 1 month) were related to antibody responses (p < 0.05).In this study, PPV23 was well tolerated, no adversereaction was reported.11 Streptococcus pneumoniae pneumonia (9.17%,11/120) occurred in the Unvaccinated group and 1 case(1.67%,1/60)in the vaccination group within one year after vaccination(Fisher's exact probability, P = 0.225). The VE was 81.79%. The per capita benefit was 39.32 dollars, thebenefit-costratio = 1.19. There are significant statistical differences between the vaccinated group and the non-vaccinated group in outpatient costs (p < 0.05, 95 %CI: 9.29-32.11), Medicine costs (p = 0.017, 95 %CI: 2.47-24.44), and disease related indirect costs (p = 0.038, 95 %CI: 0.93-33.63) within one year of vaccination. CONCLUSION: Our study results showed that PPV23 can be safely and effectively administered to HIV-1 infected individuals and effectively preventing Streptococcal pneumonia. Considering the cost-benefit of vaccination among HIV-infected persons, as it has been reported in our study, it is necessary to promote the widespread use of the vaccine among HIV-infected persons in the future.

Effect of Acupuncture on Polycystic Ovary Syndrome in Animal Models: A Systematic Review.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. As a widely used complementary and alternative therapy, acupuncture is increasingly used to treat PCOS. However, the effect of acupuncture in treating PCOS is uncertain, and the mechanisms are unclear. This systematic review aims to determine the efficacy of acupuncture on PCOS in animal preclinical models. METHODS: Experimental animal studies of acupuncture in PCOS animal models were searched in PubMed, Web of Science, China National Knowledge Infrastructure, and the Chinese Science and Technology Periodical Database from inception to December 2020. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool. RESULTS: A total of 358 studies were screened based on the title and abstract, and 31 studies were included. A total of 722 animals were involved, and all studies used either Wistar rats or SD rats. Twenty-six studies used electroacupuncture, 9 studies used manual acupuncture, and 5 of them employed both electroacupuncture and manual acupuncture. A total of 22 acupoints were involved; 7 studies followed the modern acupuncture pattern, and the rest followed classic acupuncture theory. CONCLUSIONS: The present review summarizes the current evidence of the effects of acupuncture on PCOS in animal models. Unfortunately, we could not draw a definite conclusion due to the methodological weakness of the included studies and the high heterogeneity. Well-designed studies are needed in the future to fill this gap.

[Role of skeletal muscle fat ectopic deposition in insulin resistance induced by high-fat diet].

Consumption of high-fat diet leads to the increase of fat intake and consequent excess storage of fat in the body. When the regular adipose tissues reach their capacity to store fat, ectopic fat is stored around and within non-adipose tissues, such as the liver and skeletal muscle, which plays important roles in glucose metabolism. Hence ectopic fat accumulation in major insulin target tissues is a critical determinant of insulin resistance (IR) and various related metabolic syndromes. Recent studies have shown that skeletal muscle lipid accumulation is more closely related with IR than general obesity and accounts for approximately 80%-90% type 2 diabetes, since the skeletal muscle is the largest glucose disposal site. Therefore, the association between skeletal muscle lipid and IR has attracted more and more research interest. This review summarized the role of ectopic skeletal muscle lipid in IR induced by high-fat diet and its possible mechanisms.

Source, health risk and composition impact of outdoor very fine particles (VFPs) to school indoor environment in Xi'an, Northwestern China.

Very fine particles (VFPs, PM0.25) are able to travel deeply into the respiratory tract and can produce adverse health effects, especially to children. Information on the VFPs in schools is generally lacking. We investigated the chemical compositions, sources and health risks of VFPs in a junior secondary school of Xi'an, China, during May 16th to 30th, 2012. The results showed that organic matter (37% and 39%), SO42- (13% and 11%) and geological material (20% and 24%) were the major components of VFPs both outdoors and indoors. The VFP species indoors, such as SO42- and elemental carbon, are mainly from outdoor origins, e.g. coal burning and traffic emissions. But particle resuspension by student activities, chalk dust and import from outdoors of soil dust also contributed to deteriorate air quality in the classroom. By contrast to outdoors, several indoor factors, like higher room temperature, limited volume and longer suspension time of classroom particles, can even lead to significant secondary pollutant production. Heavy metals (mainly from outside) bound to indoor VFPs are supposedly associated to non-cancer health risks, especially Pb through ingestion pathway and Mn through dermal contact. Outdoor VFPs may be associated to PAHs cancer health risks via inhalation way. This study confirms that both indoor and outdoor sources had contributions to indoor VFPs, and that VFPs health risk should be of higher concern in urban areas of Northwestern China.

Extraction of Lactobacillus acidophilus CICC 6074 S-Layer Proteins and Their Ability to Inhibit Enteropathogenic Escherichia coli.

An adhesion-related protein of Lactobacillus acidophilus strain CICC 6074 involved in binding to Caco-2 cells and inhibiting Enteropathogenic Escherichia coli (EPEC) was isolated and characterized. The S-layer protein was extracted with 5M LiCl and the active fraction purified by gel filtration (G-75). The S-layer protein was visualized by SDS-PAGE and characterized by estimating the relative molecular weight using mass spectra. The inhibitory effect of L. acidophilus and its S-layer proteins on the ability of EPEC to adhere to cells was explored by using a Caco-2 cell model. The results suggest that the S-layer proteins of L. acidophilus are adhesive in nature and are involved in the competitive exclusion of EPEC from Caco-2 cells.

Chemical profiles of urban fugitive dust PM2.5 samples in Northern Chinese cities.

Urban fugitive dust PM2.5 samples were collected in 11 selected cities in North China, and 9 ions (SO4(2-), NO3(-), Cl(-), F(-), Na(+), NH4(+), K(+), Mg(2+), and Ca(2+)) and 22 elements (Si, Al, S, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Br, Rb, Sr, Sn, Sb, Ba, and Pb) were determined to investigate chemical profiles of PM2.5. The coefficient of divergence (CD) was used to compare the similarities of the chemical profiles for fugitive dust among three regions in North China, and the results showed that their composition are quite similar. Total water soluble ions occupied 9.3% and 10.0% on average of road dust and construction dust, respectively, indicating that most of the materials in urban fugitive dust samples were insoluble. Ca(2+) was the most abundant cation and SO4(2-) dominated in anions. Soil dust loading was calculated to occupy 70.8% and 83.6% in road dust and construction dust, respectively. Ca, Si, Fe, and Al were the most abundant elements in all the samples, and Ca was absolutely the most abundant specie among the 22 detected elements in construction dust samples. Chemical species ratios were used to highlight the characteristics of urban fugitive dust by comparing with other types of aerosols. High Ca/Al ratio was a good marker to distinguish urban fugitive dust from Asian dust and Chinese loess. In addition, low K(+)/K and NO3(-)/SO4(2-), and high Zn/Al and Pb/Al ratios were good indicators to separate urban fugitive dust from desert dust, Chinese loess, or urban PM2.5 samples.

Analysis of mode-hop free tuning of folded cavity grating feedback lasers.

We analytically study an external cavity laser structure including a folded cavity. A steering mirror is utilized in the folded cavity to deflect the intracavity laser beam. A mode-hop free tuning range of ∼400 GHz can be achieved by control of the steering mirror, and a fast tuning rate is expected because of the small mass of the steering mirror. This technique has potential for applications in spectroscopy for turbulent media, especially in the mid-infrared region.

Interspecific interactions between Phragmites australis and Spartina alterniflora along a tidal gradient in the Dongtan wetland, Eastern China.

The invasive species Spartina alterniora Loisel was introduced to the eastern coast of China in the 1970s and 1980s for the purposes of land reclamation and the prevention of soil erosion. The resulting interspecific competition had an important influence on the distribution of native vegetation, which makes studying the patterns and mechanisms of the interactions between Spartina alterniora Loisel and the native species Phragmites australis (Cav.) Trin ex Steud in this region very important. There have been some researches on the interspecific interactions between P. australis and S. alterniora in the Dongtan wetland of Chongming, east China, most of which has focused on the comparison of their physiological characteristics. In this paper, we conducted a neighbor removal experiment along a tidal gradient to evaluate the relative competitive abilities of the two species by calculating their relative neighbor effect (RNE) index. We also looked at the influence of environmental stress and disturbance on the competitive abilities of the two species by comparing interaction strength (I) among different tidal zones both for P. australis and S. alterniora. Finally, we measured physiological characteristics of the two species to assess the physiological mechanisms behind their different competitive abilities. Both negative and positive interactions were found between P. australis and S. alterniora along the environmental gradient. When the direction of the competitive intensity index for P. australis and S. alterniora was consistent, the competitive or facilitative effect of S. alterniora on P. australis was stronger than that of P. australis on S. alterniora. The interspecific interactions of P. australis and S. alterniora varied with environmental conditions, as well as with the method used, to measure interspecific interactions.