Oridonin inhibits the occurrence and development of colorectal cancer by reversing the Warburg effect via reducing PKM2 dimer formation and preventing its entry into the nucleus.

BACKGROUND: The Warburg effect is prevalent in human cancer. Oridonin (ORI) has excellent anticancer effects, but its exact anticancer mechanism is still unclear. METHODS: CCK8, EdU, and flow cytometry assay were performed to detect the effect of ORI on cell viability, proliferation and apoptosis, respectively. RNA-seq was carried out to search the underlying mechanisms. Total PKM2, dimeric PKM2, nuclear PKM2 was detected by Western blot. The epidermal growth factor receptor/extracellular signal regulated kinase (EGFR/ERK) signaling was assayed. The binding ability of Importin-α5 to PKM2 was performed by Co-IP experiments. The effect of ORI combined with cysteine (Cys) or fructose-1, 6-diphosphate (FDP) on cancer cells was detected. Mouse xenograft model was established to confirm the molecular mechanisms in vivo. RESULTS: ORI inhibited viability, proliferation and promoted apoptosis of CRC cells. RNA-seq revealed ORI attenuated the Warburg effect in cancer cells. ORI reduced dimeric PKM2 and prevented it from entering the nucleus. ORI did not affect the EGFR/ERK signaling, but reduced Importin-α5 binding to the PKM2 dimer. Cys or FDP reversed or enhanced the effect of ORI. Animal model assay confirmed the molecular mechanisms in vivo. CONCLUSIONS: Our study first shows that ORI could have anticancer activity by inhibiting the Warburg effect as a novel activator of PKM2.

Convergent evolutionary shifts in rhodopsin retinal release explain shared opsin repertoires in monotremes and crocodilians.

The visual ecology of early mammals remains poorly resolved. Studies of ancestral photopigments suggest an ancient transition from nocturnal to more crepuscular conditions. By contrast, the phenotypic shifts following the split of monotremes and therians-which lost their SWS1 and SWS2 opsins, respectively-are less clear. To address this, we obtained new phenotypic data on the photopigments of extant and ancestral monotremes. We then generated functional data for another vertebrate group that shares the same photopigment repertoire as monotremes: the crocodilians. By characterizing resurrected ancient pigments, we show that the ancestral monotreme underwent a dramatic acceleration in its rhodopsin retinal release rate. Moreover, this change was likely mediated by three residue replacements, two of which also arose on the ancestral branch of crocodilians, which exhibit similarly accelerated retinal release. Despite this parallelism in retinal release, we detected minimal to moderate changes in the spectral tuning of cone visual pigments in these groups. Our results imply that ancestral forms of monotremes and crocodilians independently underwent niche expansion to encompass quickly changing light conditions. This scenario-which accords with reported crepuscular activity in extant monotremes-may help account for their loss of the ultraviolet-sensitive SWS1 pigment but retention of the blue-sensitive SWS2.

Transcriptomic profiling and differential analysis reveal the renal toxicity mechanisms of mice under cantharidin exposure.

Cantharidin (CTD), extracted from the traditional Chinese medicine mylabris, has shown significant curative effects against a variety of tumors, but its clinical application is limited by its high toxicity. Studies have revealed that CTD can cause toxicity in the kidneys; however, the underlying molecular mechanisms remain unclear. In this study, we investigated the toxic effects in mouse kidneys following CTD treatment by pathological and ultrastructure observations, biochemical index detection, and transcriptomics, and explored the underlying molecular mechanisms by RNA sequencing (RNA-seq). The results showed that after CTD exposure, the kidneys had different degrees of pathological damage, altered uric acid and creatinine levels in serum, and the antioxidant indexes in tissues were significantly increased. These changes were more pronounced at medium and high doses of CTD. RNA-seq analysis revealed 674 differentially expressed genes compared with the control group, of which 131 were upregulated and 543 were downregulated. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses showed that many differentially expressed genes were closely related to the stress response, the CIDE protein family, and the transporter superfamily, as well as the MAPK, AMPK, and HIF-1 pathways. The reliability of the RNA-seq results was verified by qRT-PCR of the six target genes. These findings offer insight into the molecular mechanisms of renal toxicity caused by CTD and provide an important theoretical basis for the clinical treatment of CTD-induced nephrotoxicity.

Higher chromosomal aberration frequency in products of conception from women older than 32 years old with diminished ovarian reserve undergoing IVF/ICSI.

Infertile women with diminished ovarian reserve (DOR) confront an increased miscarriage rate in assisted reproductive technology (ART). Genetic abnormality is the most important factor. However, the effects of DOR and female age on the molecular karyotype of products of conception (POCs) remain unknown. We analyzed POCs using a single nucleotide polymorphism (SNP) microarray from women with DOR who experienced first-trimester miscarriage in IVF/ICSI cycles. The SNP microarray revealed chromosomal abnormalities in 74.6% (47/63) of POCs, including trisomy in 83.0% (39/47). Chromosomal aberrations were more frequent in women older than 32 years old with DOR than in young women aged 20-32 years old (86.7% vs. 44.4%, P = 0.001). Univariate and multivariable analyses identified advanced age as a risk factor for chromosomal aberration-related miscarriage in women with DOR, with odds ratios of 8.125 (95% CI: 2.291-28.820, P = 0.001) and 5.867 (95% CI: 1.395-24.673, P = 0.016), respectively. The results showed that older women (older than 32 years old) with DOR had a high risk of miscarrying a chromosomally aberrant embryo/fetus, regardless of basal follicle-stimulating hormone (FSH), anti-Mullerian hormone (AMH), antral follicle count (AFC) and previous reproductive history. This finding indicates a novel cut-off value of age for women with DOR related to chromosomal aberration-related miscarriage.

Fragile Glasses Associated with a Dramatic Drop of Entropy under Supercooling.

We perform kinetic Monte Carlo simulations of a distinguishable-particle lattice model of structural glasses with random particle interactions. By varying the interaction distribution and the average particle hopping energy barrier, we obtain an extraordinarily wide range of kinetic fragility. A stretching exponent, characterizing structural relaxation, is found to decrease with the kinetic fragility in agreement with experiments. The most fragile glasses are those exhibiting low hopping barriers and, more importantly, dramatic drops of entropies upon cooling toward the glass transition temperatures. The entropy drops reduce possible kinetic pathways and lead to dramatic slowdowns in the dynamics. In addition, the kinetic fragility is shown to correlate with a thermodynamic fragility.

Yao herbal medicinal market during the Dragon Boat Festival in Jianghua County, China.

BACKGROUND: The traditional medicinal markets held during the Dragon Boat Festival are common and important in China's countryside. In Jianghua, a Yao autonomous county in Hunan Province in China, the medicinal market also plays an important role for the application, conservation, and communication of traditional Yao medicinal knowledge. METHODS: During the Dragon Boat Festival in 2016 and 2017, ethnobotanical surveys and inventories were conducted in the medicinal market of Jianghua County, and voucher plant specimens were collected, identified, and deposited in a herbarium. Quantitative analysis included measurement of frequency of occurrence for species in the marketplace and the relative importance index for the number of uses for a given species. RESULTS: A total of 306 plant species (249 genera, 113 families) and their related information about the medicinal market were collected. Some major findings include the following: (1) Using the whole plant as medicine is more common than other medicinal plant parts; (2) treating rheumatism and clearing inner heat are the most frequent medicinal uses; and (3) taking a medicinal bath is the most frequent modality to administer the traditional medicine. The frequency of occurrence and the relative importance index of some medicinal plants were analyzed, as well as the demographics and the number of stalls and the status of traditional Yao medicinal knowledge in Jianghua. Based on the investigation, suggestions were proposed for better protecting the medicinal market and preserving traditional medicinal knowledge in Jianghua County. CONCLUSION: The medicinal market during the Dragon Boat Festival in Jianghua County possesses an important cultural value and helps to conserve the traditional Yao medicinal knowledge. The medicinal plants sold at the market showed great diversity and unique local characteristics. The medicinal market is facing some challenges in such a rapidly developing era. Cultivation of young healers and maintaining the local biodiversity might be the key solutions for the development of local medicinal market and local Yao medicinal knowledge.

Production and delivery of Helicobacter pylori NapA in Lactococcus lactis and its protective efficacy and immune modulatory activity.

Helicobacter pylori neutrophil-activating protein A subunit (NapA) has been identified as a virulence factor, a protective antigen and a potent immunomodulator. NapA shows unique application potentials for anti-H. pylori vaccines and treatment strategies of certain allergic diseases and carcinomas. However, appropriate production and utilization modes of NapA still remain uncertain to date. This work has established a novel efficient production and utilization mode of NapA by using L. lactis as an expression host and delivery vector, and demonstrated immune protective efficacy and immune modulatory activity of the engineered L. lactis by oral vaccination of mice. It was observed for the first time that H. pylori NapA promotes both polarized Th17 and Th1 responses, which may greatly affect the clinical application of NapA. This report offers a promising anti-H. pylori oral vaccine candidate and a potent mucosal immune modulatory agent. Meanwhile, it uncovers a way to produce and deliver the oral vaccine and immunomodulator by fermentation of food like milk, which might have striking effects on control of H. pylori infection, gastrointestinal cancers, and Th2 bias allergic diseases, including many food allergies.

[Effects of bore diameter of porous hydroxyapatite scaffolds on three-dimensional dynamic cultivation of osteoblasts].

OBJECTIVE: To explore the relationship between bore diameter of porous hydroxyapatite (HA) scaffolds and the adhesion, proliferation and metabolism of osteoblasts by 3D cultivation. METHODS: MC3T3-E1 cell suspension was separately dropped axially through different bore diameter scaffolds (Group A:150 µm, Group B:300 µm) to confirm initial seeding. Then scaffolds were transferred into a perfusion bioreactor of 5% CO2 at 37°C for 5 days with an average flow of 3.4 ml/min. After perfusion cultivation, cell proliferation between different groups of scaffolds was determined by methyl thiazolyl tetrazolium (MTT) assay and cell metabolic activities were determined by glucose consumption. Lastly cell adhesion and proliferation were observed directly by scanning electronic microscope (SEM). RESULTS: The results of MTT assay showed that the optical density/mass ratios were 1.31 ± 0.26 in group A and 1.51 ± 0.43 in group B. There was no significant difference (t test, P = 0.36). Glucose consumption in group A was significantly lower than that in group B [(162.38 ± 33.09) vs (217.97 ± 27.91) µmol/L, P = 0.01]. The adhesion, proliferation, pseudopodia and extracellular matrix of osteoblasts in internal part of scaffolds after perfusion cultivation were observed by SEM. CONCLUSION: With excellent biocompatibility, porous HA scaffolds are available for fabricating tissue engineering bones. There is no effect of bore diameter on the proliferation of osteoblasts. But it affects the metabolic activity of osteoblasts. So bore diameter may be increased within a feasible range on the premise of mechanical properties.

Bioaugmentation of biological contact oxidation reactor (BCOR) with phenol-degrading bacteria for coal gasification wastewater (CGW) treatment.

This study was conducted to evaluate the performance of the biological contact oxidation reactor (BCOR) treating coal gasification wastewater (CGW) after augmented with phenol degrading bacteria (PDB). The PDB were isolated with phenol, 4-methyl phenol, 3,5-dimethyl phenol and resorcinol as carbon resources. Much of the refractory phenolic compounds were converted into easily-biodegradable compounds in spite of low TOC removal. The bioaugmentation with PDB significantly enhanced the removal of COD, total phenols (TP) and NH3-N, with efficiencies from 58% to 78%, 66% to 80%, and 5% to 25%, respectively. In addition, the augmented BCOR exhibited strong recovery capability in TP and COD removal while recovery of NH3-N removal needed longer time. Microbial community analysis revealed that the PDB presented as dominant populations in the bacteria consortia, which in turn determined the overall performance of the system.

Effect of powdered activated carbon technology on short-cut nitrogen removal for coal gasification wastewater.

A combined process consisting of a powdered activated carbon technology (PACT) and short-cut biological nitrogen removal reactor (SBNR) was developed to enhance the removal efficiency of the total nitrogen (TN) from the effluent of an upflow anaerobic sludge bed (UASB) reactor, which was used to treat coal gasification wastewater (CGW). The SBNR performance was improved with the increasing of COD and TP removal efficiency via PACT. The average removal efficiencies of COD and TP in PACT were respectively 85.80% and 90.30%. Meanwhile, the NH3-N to NO2-N conversion rate was achieved 86.89% in SBNR and the total nitrogen (TN) removal efficiency was 75.54%. In contrast, the AOB in SBNR was significantly inhibited without PACT or with poor performance of PACT in advance, which rendered the removal of TN. Furthermore, PAC was demonstrated to remove some refractory compounds, which therefore improved the biodegradability of the coal gasification wastewater.

[Surgical treatment for hemophilia induced lesions of foot and ankle].

OBJECTIVE: To explore perioperative management and postoperative effectiveness of hemophilia induced lesions of the foot and ankle. METHODS: Between June 1998 and February 2012, 10 cases (12 feet) of hemophilia induced lesions of the foot and ankle were treated with surgery, including 9 cases (11 feet) of hemophilia A and 1 case (1 foot) of hemophilia B. Single foot was involved in 8 cases and both feet in 2 cases, including 3 left feet and 9 right feet. All were males, aged from 13-41 years (mean, 22.6 years). Disease duration was 5-84 months (mean, 32.2 months). Preoperative American Orthopaedic Foot and Ankle Society (AOFAS) score was 43.2 +/- 21.1. Short Form 36 Health Survey Scale (SF-36) score was 45.4 +/- 20.0. All patients were given clotting factors (2 000-3 500 U) for pre-experiment and clotting factors substitution therapy was performed perioperatively. Four cases (4 feet) underwent arthrodesis, and 7 cases (8 feet) underwent Achilles tendon lengthening/tendon transposition (1 patient underwent tendon lengthening on the left foot and arthrodesis on the right foot). RESULTS: The operation time was 65-265 minutes (mean, 141.1 minutes); 1 case had 400 mL blood loss and 200 mL autogenous blood transfusion, the other cases had less than 50 mL blood loss and no blood transfusion. Wounds healed by first intention in all patients, no postoperative infection, deep vein thrombosis, or other complications occurred. All cases were followed up 6 months to 14 years and 3 months (median, 22 months). The X-ray films at last follow-up showed the patients undergoing arthrodesis obtained complete joint fusion. AOFAS scores at postoperative 6 months and last follow-up were 78.8 +/- 14.7 and 75.8 +/- 14.5, respectively; SF-36 scores were 76.6 +/- 13.1 and 75.5 +/- 13.2, respectively; and significant differences were found when compared with preoperative scores (P < 0.05), but no significant difference between postoperative 6 months and last follow-up (P > 0.05). CONCLUSION: For patients with hemophilia induced lesions of the foot and ankle, surgical treatment could relieve foot and ankle pain and improve the function. Clotting factors pre-experiment at preoperation and substitution therapy at perioperation can reduce the risk of severe postoperative hemorrhage.