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Harnessing mitochondria is considered as a promising method for biosynthesis of terpenes due to the adequate supply of acetyl-CoA and redox equivalents in mitochondria. However, mitochondrial engineering often causes serious metabolic burden indicated by poor cell growth. Here, we systematically analyzed the metabolic burden caused by the compartmentalization of the MVA pathway in yeast mitochondria for squalene synthesis. The phosphorylated intermediates of the MVA pathway, especially mevalonate-5-P and mevalonate-5-PP, conferred serious toxicity within mitochondria, which significantly compromised its possible advantages for squalene synthesis and was difficult to be significantly improved by routine pathway optimization. These phosphorylated intermediates were converted into ATP analogues, which strongly inhibited ATP-related cell function, such as mitochondrial oxidative respiration. Fortunately, the introduction of a partial MVA pathway from acetyl-CoA to mevalonate in mitochondria as well as the augmentation of the synthesis of mevalonate in cytosol could significantly promote the growth of yeasts. Accordingly, a combinatorial strategy of cytoplasmic and mitochondrial engineering was proposed to alleviate the metabolic burden caused by the compartmentalized MVA pathway in mitochondria and improve cell growth. The strategy also displayed the superimposed effect of cytoplasmic engineering and mitochondrial engineering on squalene production. Through a two-stage fermentation process, the squalene titer reached 21.1 g/L with a specific squalene titer of 437.1 mg/g dcw, which was the highest at present. This provides new insight into the production of squalene and other terpenes in yeasts based on the advantages of mitochondrial engineering.

Patchoulol is a tricyclic sesquiterpene widely used in perfumes and cosmetics. Herein, comprehensive engineering strategies were employed to construct an efficient yeast strain for patchoulol production. First, a platform strain was constructed via pathway modification. Second, three off-pathway genes were deleted, which led to significant physiological changes in yeast. Further, strengthening of the ergosterol pathway, enhancement of the energy supply, and a decrease in intracellular reactive oxygen species were implemented to improve the physiological status of yeast, demonstrating a new promotive relationship between ergosterol biosynthesis and synthesis of patchoulol. Moreover, patchoulol synthase was improved through protein modification and Mg2+ addition, reaching a final titer of 141.5 mg/L in a shake flask. Finally, a two-stage fermentation with dodecane addition was employed to achieve the highest production (1632.0 mg/L, 87.0 mg/g dry cell weight, 233.1 mg/L/d) ever reported for patchoulol in a 5 L bioreactor. This work lays a foundation for green and efficient patchoulol production.

Exercise (Ex) has long been recognized to produce beneficial effects on hypertension (HTN). This coupled with evidence of gut dysbiosis and an impaired gut-brain axis led us to hypothesize that reshaping of gut microbiota and improvement in impaired gut-brain axis would, in part, be associated with beneficial influence of exercise. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise for 12 weeks, whereas, detrained groups underwent 8 weeks of moderate-intensity exercise followed by 4 weeks of detraining. Fecal microbiota, gut pathology, intestinal inflammation, and permeability, brain microglia and neuroinflammation were analyzed. We observed that exercise training resulted in a persistent decrease in systolic blood pressure in the SHR. This was associated with increase in microbial α diversity, altered β diversity, and enrichment of beneficial bacterial genera. Furthermore, decrease in the number of activated microglia, neuroinflammation in the hypothalamic paraventricular nucleus, improved gut pathology, inflammation, and permeability were also observed in the SHR following exercise. Interestingly, short-term detraining did not abolish these exercise-mediated improvements. Finally, fecal microbiota transplantation from exercised SHR into sedentary SHR resulted in attenuated SBP and an improved gut-brain axis. These observations support our concept that an impaired gut-brain axis is linked to HTN and exercise ameliorates this impairment to induce antihypertensive effects.

Lipodermatosclerosis (LDS) is a serious skin change associated with the progression of chronic venous insufficiency (CVI) of the lower extremities, and can be clinically divided into acute phase, subacute phase and chronic phase. The disease is common in middle-aged women, prone to occur in the lower leg 1/3, clinical manifestations of the skin flake erythema, induration, pigmentation, skin rough and thickening. The patients often suffer from secondary infection after scratching due to pruritus. The severe ones can form refractory ulcer or even cause skin necrosis, and may be canceration. At present, domestic reports on LDS are less, the clinical manifestations, etiology, pathogenesis and treatment of the LDS are reviewed in present paper, in order to strengthen the understanding of LDS and provide the evidence for clinical diagnosis and treatment of LDS. DOI: 10.11855/j.issn.0577-7402.2020.07.16

The study aims to enhance β-amyrin production in

Patchoulol is a tricyclic sesquiterpene widely used in perfumes and cosmetics. Herein, comprehensive engineering strategies were employed to construct an efficient yeast strain for patchoulol production. First, a platform strain was constructed

Gut dysbiosis and dysregulation of gut–brain communication have been identified in hypertensive patients and animal models. Previous studies have shown that probiotic or prebiotic treatments exert positive effects on the pathophysiology of hypertension. This study aimed to examine the hypothesis that the microbiota-gut-brain axis is involved in the antihypertensive effects of curcumin, a potential prebiotic obtained from Curcuma longa. Male 8- to 10-week-old spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were divided into four groups: WKY rats and SHRs treated with vehicle and SHRs treated with curcumin in dosage of 100 or 300 mg/kg/day for 12 weeks. Our results show that the elevated blood pressure of SHRs was markedly decreased in both curcumin-treated groups. Curcumin treatment also altered the gut microbial composition and improved intestinal pathology and integrity. These factors were associated with reduced neuroinflammation and oxidative stress in the hypothalamus paraventricular nucleus (PVN). Moreover, curcumin treatment increased butyrate levels in the plasma, which may be the result of increased butyrate-producing gut microorganisms. In addition, curcumin treatment also activated G protein-coupled receptor 43 (GPR 43) in the PVN. These results indicate that curcumin reshapes the composition of the gut microbiota and ameliorates the dysregulation of the gut-brain communication to induce antihypertensive effects.

The hypothalamic paraventricular nucleus (PVN) plays crucial roles in central cardiovascular regulation. Increasing evidence in humans and rodents shows that vitamin D intake is important for achieving optimal cardiovascular function. The purpose of this study was to investigate whether calcitriol, an active form of vitamin D, improves autonomic and cardiovascular function in hypertensive rats and whether PVN oxidative stress and inflammation are involved in these beneficial effects. Male spontaneously hypertensive rats (SHR) and normotensive control Wistar Kyoto (WKY) rats were treated with either calcitriol (40 ng/day) or vehicle (0.11 μL/h) through chronic PVN infusion for 4 weeks. Blood pressure and heart rate were recorded continuously by radiotelemetry. PVN tissue, heart and plasma were collected for molecular and histological analysis. Compared to WKY rats, SHR exhibited increased systolic blood pressure, sympathetic drive, and cardiac hypertrophy and remodeling. These were associated with higher mRNA and protein expression levels of high mobility box 1 (HMGB1), receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), proinflammatory cytokines, NADPH oxidase subunit in the PVN. In addition, increased norepinephrine in plasma, elevated reactive oxygen species levels and activation of microglia in the PVN were also observed in SHR. Chronic calcitriol treatment ameliorated these changes but not in WKY rats. Our results demonstrate that chronic infusion of calcitriol in the PVN ameliorates hypertensive responses, sympathoexcitation and retains cardiovascular function in SHR. Reduced inflammation and oxidative stress within the PVN are involved in these calcitriol-induced effects.

In view of the high order, nonlinear characteristics of target trajectory, control strategy is proposed for a kind of RBF neural network and polynomial interpolation combining. According to the specific requirements of trajectory planning, the manipulator in joint space variables are expressed as one or two order derivative function by polynomial interpolation algorithm, then the RBF neural network is used for tracking the target trajectory. Finally, through MATLAB simulation, the accuracy of this method is verified.

Calcium sulfate is an important inorganic chemical products which is widely used in construction, pharmaceutical and food industries. Especially, calcium sulfate whisker with fibrous structure developed in recent years is further used in rubber, coating, plastic, adhesives, textile, papermaking, and many other industries due to its superior performance and characteristics of environmental protection and nontoxic.The paper reviewed the preparation technology of calcium sulfate according to the different raw materials, especially for industrial waste (by-product).

A facile method for manufacturing super hydrophobic surfaces is presented using the stainless steel wire mesh as templates. The rough surfaces of polymers including polycarbonate, polypropylene and PMMA are prepared with hot embossing on different specifications of stainless steel wire mesh. Scanning electron microscopy (SEM) results reveal that the surfaces roughness of the polymers can be controlled by selecting templates. Contact angle measurement shows that the water contact angles(WCA) rise with the increase of surface roughness, especially, the water contact angle on the PC surfaces prepared with specifications of 635mesh screen can reach to 152.3°, alias super hydrophobic surfaces.

Superhydrophobic materials can be used in building materials, such as glass, ceramics, and concrete, which keep buildings clean. Slip phenomenon plays an important role on the hydrophobic of solid surface. Based on the model of Volume of Fluid (VOF) for given inlet velocity and outlet pressure, the unilateral slip flow of three typical physical models (rectangular, triangular and round head shape physical model) in superhydrophobic microchannel are numerically simulated. Furthermore, the hydrophobic laws are analyzed in the condition of different shapes and dimensions, and the optimal dimension and shape of microstructure is obtained. Numerical simulation results show that the slip happens in the air-liquid interface of the microchannel, and when the micro rib’s height is 40μm, the slip velocity for rectangular physical model reaches to 125mm/s. When the micro rib’s height is at 50μm-100μm, the round head shape physical model has the largest slip velocity of 350mm/s. This study plays an important guiding role for the design and application of the superhydrophobic surface.

To explore the factors influencing cognitive functions in patients with childhood and adolescence-onset schizophrenia.The clinical data of 78 patients with childhood and adolescence-onset schizophrenia who met with the criteria of ICD-10 for schizophrenia were retrospectively reviewed. The cognitive functions were evaluated by the Chinese Wechsler Intelligence Scale for Children (C-WISC), the Wisconsin Card Sorting Test (WCST), digit span backward and P300. The clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS).The patients with a lower education level or earlier onset of age had a longer P3 latency at the P300Fz area. The patients with a higher parental education level had higher scores of full intelligence quotient (FIQ), verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), conceptual level and completed categories of WCST and backward numeric order reciting. The patients with higher PANSS negative subscale scores had lower scores of FIQ, VIQ, PIQ, completed categories and conceptual level of WCST and backward numeric order reciting. The patients with a longer stabilization time had higher backward numeric order reciting scores.The severity of negative symptoms of the patients and the educational level of their parents are major factors influencing cognitive functions in patients with childhood and adolescence-onset schizophrenia.

Telomere length has been reported as potentially biomarker and prognostic indicator in cancer. Our goal was to evaluate whether DNA storage/handling or sample source would result in fragmented telomere DNA using an established QPCR-based telomere assay that quantifies the length of telomeres (Cawthon 2002) Because the effect of storage conditions on telomere length has not been thoroughly evaluated, we were concerned that the QPCR could misclassify telomere length and lead to misleading epidemiological results. Genomic DNA samples for this preliminary study were gathered from either The Nurses Health Study, healthy volunteers, the MDA-MB-231 cell line (human breast cancer), and a commercial source (Promega). To create a model system of degraded DNA, the DNA were either subjected to multiple freeze thaws (FT, Due to the repetitive nature of the telomeric sequence, we expected to see discrete amplicon sizes starting at 76 Bp reaching over hundreds of Bps. Bioanalyzer electropherograms indicated that eight to twelve major products of ∼8 Bp iterations are commonly produced up to 150 Bp with some minor products In summary, under the current experimental conditions, the QPCR assay does not generate sufficient variable length amplicons as to present a measurable metric using the Bioanalyzer. Elevated Ct values do seem to correlate with the presence of degraded DNA, and therefore suggest under the conditions used multiple FTs and sonication do not damage the telomeric sequences. However this assay design cannot currently determine the relative contribution of full length vs. degraded telomeric sequence to the Ct value. Further investigation is warranted before this assay becomes clinically diagnostic or prognostic. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C27.