RNA polymerase I subunit D activated by Yin Yang 1 transcription promote cell proliferation and angiogenesis of colorectal cancer cells.

This study aims to explore possible effect of RNA polymerase I subunit D (POLR1D) on proliferation and angiogenesis ability of colorectal cancer (CRC) cells and mechanism herein. The correlation of POLR1D and Yin Yang 1 (YY1) expressions with prognosis of CRC patients in TCGA database was analyzed. Quantitative realtime polymerase chain reaction (qRT-PCR) and Western blot were applied to detect expression levels of POLR1D and YY1 in CRC cell lines and CRC tissues. SW480 and HT- 29 cells were transfected with si-POLR1D or pcDNA3.1-POLR1D to achieve POLR1D suppression or overexpression before cell migration, angiogenesis of human umbilical vein endothelial cells were assessed. Western blot was used to detect expressions of p38 MAPK signal pathway related proteins and interaction of YY1 with POLR1D was confirmed by dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP). TCGA data showed that both POLR1D and YY1 expressions were up-regulated in CRC patients. High expression of POLR1D was associated with poor prognosis of CRC patients. The results showed that POLR1D and YY1 were highly expressed in CRC cell lines. Inhibition or overexpression of POLR1D can respectively suppress or enhance proliferation and angiogenesis of CRC cells. YY1 inhibition can suppress CRC progression and deactivate p38 MAPK signal pathway, which can be counteracted by POLR1D overexpression. JASPAR predicted YY1 can bind with POLR1D promoter, which was confirmed by dual luciferase reporter gene assay and ChIP. YY1 transcription can up-regulate POLR1D expression to activate p38 MAPK signal pathway, thus promoting proliferation and angiogenesis ability of CRC cells.

Effects of Extracellular Polymeric Substances on the Formation and Methylation of Mercury Sulfide Nanoparticles.

Growing evidence has suggested that microbial biofilms are potential environmental "hotspots" for the production and accumulation of a bioaccumulative neurotoxin, methylmercury. Here, we demonstrate that extracellular polymeric substances (EPS), the main components of biofilm matrices, significantly interfere with mercury sulfide precipitation and lead to the formation of nanoparticulate metacinnabar available for microbial methylation, a natural process predominantly responsible for the environmental occurrence of methylmercury. EPS derived from mercury methylating bacteria, particularly Desulfovibrio desulfuricans ND132, substantially increase the methylation potential of nanoparticulate mercury. This is likely due to the abundant aromatic biomolecules in EPS that strongly interact with mercury sulfide via inner-sphere complexation and consequently enhance the short-range structural disorder while mitigating the aggregation of nanoparticulate mercury. The EPS-elevated bioavailability of nanoparticulate mercury to D. desulfuricans ND132 is not induced by dissolution of these nanoparticles in aqueous phase, and may be dictated by cell-nanoparticle interfacial reactions. Our discovery is the first step of mechanistically understanding methylmercury production in biofilms. These new mechanistic insights will help incorporate microbial EPS and particulate-phase mercury into mercury methylation models, and may facilitate the assessment of biogeochemical cycling of other nutrient or toxic elements driven by EPS-producing microorganisms that are prevalent in nature.

Short-course versus long-course antibiotics in prosthetic joint infections: a systematic review and meta-analysis of one randomized controlled trial plus nine observational studies.

BACKGROUND: Prosthetic joint infections (PJIs) often require long-course antibiotic therapy. However, recent studies argue against the current practice and raise concerns such as the development of antibiotic resistance, side effects of medications and medical costs. OBJECTIVES: To review and compare the outcomes of short-course and long-course antibiotics in PJIs. METHODS: We conducted a systemic review and meta-analysis using a predefined search term in PubMed and EMBASE databases. Studies that met the inclusion criteria from inception to June 2018 were included. The quality of the included studies was assessed. RESULTS: A total of 10 articles and 856 patients were analysed, comprising 9 observational studies and 1 randomized controlled trial. Our meta-analysis showed no significant difference between short-course and long-course antibiotics (relative risk = 0.87, 95% CI = 0.62-1.22). Additionally, the older the studied group was, the more short-course antibiotics were favoured. CONCLUSIONS: When treating PJI patients following debridement, antibiotics and implant retention, an 8 week course of antibiotic therapy for total hip arthroplasty and a 75 day course for total knee arthroplasty may be a safe approach. For two-stage exchange, a shorter duration of antibiotic treatment during implant-free periods is also generally safe with the usage of antibiotic-loaded cement spacers.

Label-free detection of the cytotoxicity effect of cisplatin in human leukemic cells using Raman spectroscopy in conjunction with multivariate analysis.

The single-cell Raman spectra of human leukemic Jurkat cells can be obtained by confocal microscopy Raman spectroscopy, including cell groups treated with different doses of cisplatin (0, 3.5, 7, 10.5 and 14 µmol L-1) for 24 hours and those treated with 10.5 µmol L-1 cisplatin for different times (0, 6, 12, 24 and 36 hours). The structure and amount of protein, nucleic acid and other major molecules from different cell groups show special changes in the percentage of biochemical constituents. Compared with the control group, the two protein Raman bands (1449 and 1659 cm-1) and two DNA bands (1303 and 1338 cm-1) in the treatment groups decrease in intensity with the increase of the drug dose and treatment time of cisplatin. Partial least squares combined with support vector machines was used to develop diagnostic algorithms for distinguishing between control and treatment groups. The support vector machines for classification between the control group (0 µmol L-1) and cell groups treated with 10.5 and 14 µmol L-1 cisplatin for 24 hours have achieved good diagnostic results with a high sensitivity of 100%, specificity of 100% and accuracy of 100%, respectively, indicating that 10.5 µmol L-1 can be used as an appropriate therapeutic dose. Using the same method, the diagnostic sensitivity, specificity and accuracy between the control group (0 hours) and cell groups treated with 10.5 µmol L-1 cisplatin for 24 and 36 hours are all 100%, showing that 24 hours can be used as an appropriate therapeutic time. These results showed that Raman spectroscopy in conjunction with multivariate statistical analysis could be a useful tool for evaluating the cytotoxicity induced by cisplatin in human leukemic cells.

microRNA-143 interferes the EGFR-stimulated glucose metabolism to re-sensitize 5-FU resistant colon cancer cells via targeting hexokinase 2.

5-Fluorouracil (5-FU) is one of the frequently used chemotherapeutic agents against colorectal cancer (CRC). However, 5-FU treatment remains clinical challenges since a large fraction of patients with CRC developed resistance to 5-FU-based chemotherapies. Hexokinase 2 (HK II), coding for a rate-limiting enzyme of glutamine metabolism, is responsible for the dysregulated glycolysis of cancers. In this study, we report epidermal growth factor receptor (EGFR) and HK II were overexpressed in colon cancers and positively correlated with 5-FU resistance of CRC. In addition, expression of miR-143 was remarkedly suppressed in 5-FU resistant CRC patients and colon cancer cells. Moreover, miR-143 expression was effectively downregulated by EGFR and inversely associated with HK II expression in CRC cells. We identified HK II as a direct target of miR-143 in colon cancer cells. Overexpression of miR-143 inhibited glycolysis rate through direct targeting HK II, leading to re-sensitization of 5-FU resistant colon cancer cells to 5-FU treatment. Rescue experiments validated that recovering HK II in miR-143-overexpressing cells restored 5-FU resistance of CRC cells. In general, our study reveals critical roles of miR-143, which is a downstream effector of EGFR in 5-FU resistant CRC cells through direct targeting HK II, indicating miR-143 is an effectively therapeutic target for the treatment of patients with chemoresistant CRC.

Effects of early PCSK9 inhibitor application on inflammation levels and microcirculatory function after PCI in patients with NSTE-ACS.

OBJECTIVE: To investigate inflammation levels and microcirculatory function following the early application of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor after percutaneous coronary intervention (PCI) in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS). METHODS: This is a retrospective study. Between December 2019 and December 2021, 120 patients with NSTE-ACS admitted to the People's Hospital of Henan University of Traditional Chinese Medicine for PCI were randomized via a web-based randomization system into a control group (60 cases) treated with atorvastatin or a PCSK9 inhibitor group (60 cases) treated with atorvastatin + evolocumab. After 6 months of treatment, between-group differences were assessed for the following measures: triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), index of microcirculatory resistance (IMR), Thrombosis in Myocardial Infarction myocardial perfusion grading (TMPG), major adverse cardiovascular events (MACEs), and adverse reactions. RESULTS: After 6 months of treatment, TG (P=0.037), TC (P<0.001), LDL-C (P<0.001), Lp(a) (P<0.001), hs-CRP (P<0.001), TNF-α (P<0.001), and IL-6 (P<0.001) levels and IMR values (P<0.001) were significantly lower in the PCSK9 inhibitor group than in the control group. TMPG grade 3 (P=0.04) was noted to occur significantly more frequently in the PCSK9 inhibitor group than in the control group. No significant between-group differences in MACEs (P>0.05) or adverse reactions (P>0.05) were observed. CONCLUSIONS: Compared with statins alone, a PCSK9 inhibitor combined with statins improves inflammation levels and microcirculatory function after PCI in patients with NSTE-ACS, and this strategy deserves clinical attention.

Changing surface ocean circulation caused the local demise of echinoid Scaphechinus mirabilis in Taiwan during the Pleistocene-Holocene transition.

Abundant fossil specimens of Scaphechinus mirabilis, now occurring mostly in temperate waters, have been found in the Toukoshan Formation (Pleistocene) in Miaoli County, Taiwan. Environmental changes leading to its extirpation (local extinction) have thus far been elusive. Here, we reconstruct past environmental and oceanic conditions off northwest Taiwan by analyzing clumped isotopes, as well as stable oxygen isotopes, of well-preserved fossil echinoid tests collected from the Toukoshan Formation. Radiocarbon dates suggest that these samples are from Marine Isotope Stage 3 (MIS 3). Paleotemperature estimates based on clumped isotopes indicate that fossil echinoids were living in oceanic conditions that range from 9 to 14 °C on average, comparable with the estimate derived for a modern sample from Mutsu Bay, Japan. Notably, this temperature range is ~ 10 °C colder than today's conditions off northwest Taiwan. The substantially lower temperatures during ~ 30 ka (MIS 3) compared to the modern conditions might be due to the rerouting of surface currents off northwest Taiwan when the sea level was ~ 60 m lower than today, in addition to the cooling caused by a lower atmospheric CO2 level during the Last Glacial Period. Colder waters brought here by the China Coastal Current (CCC) and the existence of shallow subtidal zones termed "Miaoli Bay" (mainly located in the present-day Miaoli county) during MIS 3 plausibly sustained generations of S. mirabilis, yielding tens of thousands of fossil specimens in the well-preserved fossil beds. The likely extirpation driver is the drastic change from a temperate climate to much warmer conditions in the shallow sea during the Pleistocene-Holocene transition.

Inhibiting roles of FOXA2 in liver cancer cell migration and invasion by transcriptionally suppressing microRNA-103a-3p and activating the GREM2/LATS2/YAP axis.

Forkhead box A2 (FOXA2) has emerged as a tumor inhibitor in several human malignancies. This work focused on the effect of FOXA2 on liver cancer (LC) cell invasion and migration and the involving molecules. FOXA2 expression in LC tissues and cell lines was determined. The potential target microRNA (miRNA) of FOXA2 was predicted via bioinformatic analysis and validated through a ChIP assay. The mRNA target of miRNA-103a-3p was predicted via bioinformatic analysis and confirmed via a luciferase assay. Altered expression of FOXA2, miR-103a-3p and GREM2 was introduced in cells to identify their roles in LC cell migration and invasion. Consequently, FOXA2 and GREM2 were poorly expressed while miR-103a-3p was highly expressed in LC samples. Overexpression of FOXA2 or GREM2 suppressed migration and invasion of LC cells, while up-regulation of miR-103a-3p led to inverse trends. FOXA2 transcriptionally suppressed miR-103a-3p to increase GREM2 expression. Silencing of GREM2 blocked the effects of FOXA2. GREM2 increased LATS2 activity and YAP phosphorylation and degradation. To conclude, this study demonstrated that FOXA2 suppressed miR-103a-3p transcription to induce GREM2 upregulation, which increased LATS2 activity and YAP phosphorylation to inhibit migration and invasion of LC cells.

Enhanced oxygen reducing biocathode electroactivity by using sediment extract as inoculum.

Autotrophic bacteria are able to catalyze cathodic oxygen reduction as a renewable and sustainable inexpensive catalyst. However, the performance of biocathode varied over reactors, and we still not know how inoculums affect this system. Using three different inoculum of wastewater (WW), sediment extract (SE) and soil extract (SO) in parallel reactors, we found that SE achieved the shortest setup time (17-25% shorter) as well as the highest power density compared to those of SO and WW. Cyclic voltammetry (CV) further revealed that the current densities of SE biocathodes (100±1A/m3) was 150% and 67% higher than those of WW biocathodes (40±1A/m3) and SO biocathodes (65±1A/m3). Community analysis showed the selective pressure on biocathode facilitated the growth of Proteobacteria, Bacteroidetes, Firmicutes and Actinobacteria families. Different from WW and SO biocathodes, Nitrospirae was selectively enriched in SE biocathodes, corresponding to an obvious increase in Unidentified Nitrospiraceae population at genus level, which may play an important role on the cathodic electroactivity. These results confirmed that sediment extract is a better bacteria source than soil and wastewater for the acclimation of autotrophic electroactive bacteria, and the community comparison provided broader knowledge on biocathode microbiology.

[Multifactorial analysis of the risk factors of chronic prostatitis].

OBJECTIVE: To investigate the risk factors of chronic prostatitis. METHODS: An epidemiological survey of 1,168 patients with chronic prostatitis was conducted and both single factor and multifactorial logistic regression analyses were performed. RESULTS AND CONCLUSION: Many risk factors were identified, including urethritis, uncontrolled sexual activity, frequent masturbation, urinary system injury, fixed body posture (especially long-time riding), excessive drinking, long-time holding urine. The findings may provide reference for the prevention, treatment and measures for coping with recurrence of chronic prostatitis.

NMR studies on effects of tetraalkylammonium bromides on micellization of sodium dodecylsulfate.

The effects of tetraalkylammonium bromides (TAABs) on the micellization of sodium dodecylsulfate (SDS) are studied using pyrene solubilization and several nuclear magnetic resonance (NMR) techniques. Two-dimensional nuclear Overhauser effect spectroscopy (2D NOESY) experiments confirm that tetraalkylammonium (TAA(+)) ions associate with SDS to form mixed micelles. TAA(+) ions attach to the surface of the mixed micelles and become inserted into the hydrophobic core of the mixed micelles. Because TAA(+) ions appear in the hydrophobic interior of the TAA-SDS mixed micelles, the micropolarity inside the mixed micelles sensed by pyrene might not reflect the true hydrophobicity of the micellar core. Using proton chemical shift analysis, the degree of hydration on the surface of the mixed micelles is determined from the chemical shift change of SDS α-CH2 protons. The self-diffusion coefficients of SDS and TAA(+) ions in the TAAB/SDS/D2O solutions are measured by using pulse-field gradient NMR, and the fraction of TAA(+) ions associated with the SDS to form the mixed micelles is calculated from the self-diffusion data. Moreover, secondary micelle formation for SDS and TAA(+) ions is observed on the basis of (1)H chemical shift analysis and the self-diffusion data. The 2D NOESY experiments also reveal unusual tumbling behavior of SDS alkyl protons. For Pr4NBr/SDS and Bu4NBr/SDS solutions, positive and negative nuclear Overhauser effects are simultaneously observed among the SDS alkyl protons.

Biological characterization of oxidized hyaluronic acid/resveratrol hydrogel for cartilage tissue engineering.

Osteoarthritis is a type of arthritis that is caused by breakdown of cartilage, with eventual loss of the cartilage of the joints. The ability of self-repair in damaged cartilage tissue is limited; the aim of this work is to fabricate and characterize an oxidized hyaluronic acid/resveratrol (Oxi-HA/Res) hydrogel for future applications in cartilage tissue engineering. Under physiological conditions, the Oxi-HA/Res hydrogel was prepared by chemical crosslinking of Oxi-HA with resveratrol solution and characterized by Fourier transform infrared spectrometry assay; the biocompatibility and gene expression of chondrocytes within the Oxi-HA-Res hydrogel then analyzed. The cell viability and cytotoxicity assays showed that the Oxi-HA/Res hydrogel has good biocompatibility. Oxi-HA/Res hydrogel can upregulate expression of type II collagen, aggrecan, and Sox-9 genes; while down-regulating IL-1ß, MMP-1, MMP-3, MMP13 gene expression. It can also reduce LPS-induced inflammation and chondrocyte damage. The results of this study showed that the Oxi-HA/Res hydrogel is biocompatible with chondrocytes, allows for extracellular matrix synthesis, and also reduce LPS-induced inflammation and damage. These results suggest that Oxi-HA/Res hydrogel may be a potential suitable cell carrier for chondrocyte cells in the treatment of cartilage defect. However, further in vivo study is mandatory for future possible clinical applications.

Supervised aerobic exercise is more effective than home aerobic exercise in female chinese patients with rheumatoid arthritis.

OBJECTIVE: To compare the effectiveness and safety of supervised aerobic exercise and home aerobic exercise in female Chinese patients with rheumatoid arthritis. DESIGN: Single-blind randomized controlled trial. SUBJECTS: Thirty female Chinese patients with rheumatoid arthritis were assigned to either supervised aerobic exercise or home aerobic exercise groups. METHODS: The supervised aerobic exercise programme was supervised by a physical therapist, while the home aerobic exercise programme was performed at home after one session of exercise instruction. Each programme consisted of 1 h of aerobic exercise conducted 3 times per week for 8 weeks. Aerobic capacity and disease-related variables, including pain intensity, functional ability, psychological status and joint function, were measured. RESULTS: Significant difference in changed score between pre- and post-exercise data was observed between the supervised aerobic exercise and home aerobic exercise groups regarding aerobic capacity (p < 0.0001). Pre- and post-exercise within-group comparisons showed significant improvement (20%) in aerobic capacity only in the supervised aerobic exercise group. Pre- and post-exercise within-group comparison showed significant improvement in 5 and 3 items of disease-related variables in supervised aerobic exercise and home aerobic exercise groups, respectively. CONCLUSION: An 8-week supervised aerobic exercise programme induced significant improvement in the aerobic capacity of female Chinese patients with rheumatoid arthritis, and was superior to a home aerobic exercise programme. Both programmes of aerobic exercise were safe for female Chinese patients with rheumatoid arthritis.