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TRANSFER MATRIX METHOD FOR MULTIBODY SYSTEMS: THEORY AND APPLICATIONS Xiaoting Rui, Guoping Wang and Jianshu Zhang - Nanjing University of Science and Technology, China  Featuring a new method of multibody system dynamics, this book introduces the transfer matrix method systematically for the first time.

Whole genome metagenomic sequencing is a powerful platform enabling the simultaneous identification of all genes from entirely different kingdoms of organisms in a complex sample. This technology has revolutionised multiple areas from microbiome research to clinical diagnoses. However, one of the major challenges of a metagenomic study is the overwhelming non-microbial DNA present in most of the host-derived specimens, which can inundate the microbial signals and reduce the sensitivity of microorganism detection. Various host DNA depletion methods to facilitate metagenomic sequencing have been developed and have received considerable attention in this context. In this review, we present an overview of current host DNA depletion approaches along with explanations of their underlying principles, advantages and disadvantages. We also discuss their applications in laboratory microbiome research and clinical diagnoses and, finally, we envisage the direction of the further perfection of metagenomic sequencing in samples with overabundant host DNA.

ObjectiveCigarette smoking is a major risk factor for colorectal cancer (CRC). We aimed to investigate whether cigarette smoke promotes CRC by altering the gut microbiota and related metabolites.DesignAzoxymethane-treated C57BL/6 mice were exposed to cigarette smoke or clean air 2 hours per day for 28 weeks. Shotgun metagenomic sequencing and liquid chromatography mass spectrometry were parallelly performed on mice stools to investigate alterations in microbiota and metabolites. Germ-free mice were transplanted with stools from smoke-exposed and smoke-free control mice.ResultsMice exposed to cigarette smoke had significantly increased tumour incidence and cellular proliferation compared with smoke-free control mice. Gut microbial dysbiosis was observed in smoke-exposed mice with significant differential abundance of bacterial species including the enrichment of Eggerthella lenta and depletion of Parabacteroides distasonis and Lactobacillus spp. Metabolomic analysis showed increased bile acid metabolites, especially taurodeoxycholic acid (TDCA) in the colon of smoke-exposed mice. We found that E. lenta had the most positive correlation with TDCA in smoke-exposed mice. Moreover, smoke-exposed mice manifested enhanced oncogenic MAPK/ERK (mitogen-activated protein kinase/extracellular signal‑regulated protein kinase 1/2) signalling (a downstream target of TDCA) and impaired gut barrier function. Furthermore, germ-free mice transplanted with stools from smoke-exposed mice (GF-AOMS) had increased colonocyte proliferation. Similarly, GF-AOMS showed increased abundances of gut E. lenta and TDCA, activated MAPK/ERK pathway and impaired gut barrier in colonic epithelium.ConclusionThe gut microbiota dysbiosis induced by cigarette smoke plays a protumourigenic role in CRC. The smoke-induced gut microbiota dysbiosis altered gut metabolites and impaired gut barrier function, which could activate oncogenic MAPK/ERK signalling in colonic epithelium.

An isolated two-dimensional circular cylinder with two linear degrees of freedom, parallel and perpendicular to the free-stream direction, and owning a nonlinear energy sink (NES) is investigated by fluid–structure interaction (FSI) simulations to assess vortex-induced vibrations (VIV) at moderate Reynolds numbers. Subsequently, the wake-induced vibration (WIV) of a pair of identical cylinders under the action of two NES in a tandem arrangement and in a proximity–wake interference regime is explored using the same approach. The NES parameters (mass, nonlinear stiffness and damping) are investigated to determine their effects on the dynamic response of a single degree of freedom (in transverse flow direction) coupled system by a reduced-order model based on an experimentally validated van der Pol oscillator. The CFD model coupled with FSI method is also validated against VIV experimental data for an isolated cylinder in a uniform flow. The study is aimed to investigate the effect of the passive suppression NES device on VIV and WIV. The amplitude response, trajectories of cylinder motion and temporal evolutions of vortex shedding are obtained by conducting a series of numerical simulations. It is found that placing a tuned NES in the cylinders can provide good suppression effect; however, the effectiveness is function of the reduced velocity.

Targeting immune cells or factors are effective for patients with solid tumors. Myeloid-derived suppressor cells (MDSCs) are known to have immunosuppressive functions, and the levels of MDSCs in patients with solid tumor are assumed to have prognostic values. This meta-analysis aimed at evaluating the relationship between MDSCs and the prognosis of patients with solid tumors. We searched articles in PUBMED and EMBASE comprehensively, updated to March 2016. Eight studies with 442 patients were included in the meta-analysis. We analyzed pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). The results showed that MDSCs were associated with poor OS (HR, 1.94; 95% confidence interval [CI], 1.42-2.66; P < 0.0001) in patients with solid tumors. PFS/RFS (HR, 1.85; 95% CI, 1.16-2.97; P = 0.01) also indicated the association between MDSCs and prognosis. The HRs and 95% CIs for OS in Asian and non-Asian patients were 2.53 (95% CI 1.61-3.42, p < 0.00001) and 1.67 (95% CI 1.14-2.46, p < 0.0001), respectively. We further analyzed the data according to tumor types. The combined HRs and 95% CIs for OS were 1.26 (95% CI 1.10-1.44, p = 0.0003) for gastrointestinal (GI) cancer, 2.59 (95% CI 1.69-3.98, p < 0.0001) for hepatocellular carcinoma (HCC) and 1.86 (95% CI 1.26-2.75, p = 0.002) for other tumor types. In conclusion, MDSCs had a fine prognostic value for OS and PFS/RFS in patients with solid tumors. MDSCs could be used as biomarkers to evaluate prognosis in clinical practice.

β-glucosidases (BGLs) play a crucial role in the degradation of lignocellulosic biomass as well as in industrial applications such as pharmaceuticals, foods, and flavors. However, the application of BGLs has been largely hindered by issues such as low enzyme activity, product inhibition, low stability, etc. Many approaches have been developed to engineer BGLs to improve these enzymatic characteristics to facilitate industrial production. In this article, we review the recent advances in BGL engineering in the field, including the efforts from our laboratory. We summarize and discuss the BGL engineering studies according to the targeted functions as well as the specific strategies used for BGL engineering.

Background Innate immunity can facilitate early brain injury (EBI) following subarachnoid hemorrhage (SAH). Numerous studies suggest that pyroptosis could exacerbate extracellular immune responses by promoting secretion of inflammatory cytokines. Transforming growth factor-β-activated kinase 1 (TAK1) is a quintessential kinase that positively regulates inflammation through NF-κB and MAPK signaling cascades. However, the effects of TAK1 on neuroinflammation in EBI following SAH are largely unknown. Methods Two hundred and forty-six male C57BL/6J mice were subjected to the endovascular perforation model of SAH. A selective TAK1 inhibitor, 5Z-7-oxozeaenol (OZ) was administered by intracerebroventricular (i.c.v) injection at 30 min after SAH induction. To genetic knockdown of TAK1, small interfering RNA (siRNA) was i.c.v injected at 48 h before SAH induction. SAH grade, brain water content, BBB permeability, neurological score, western blot, real-time PCR, ELISA, transmission electron microscope, and immunofluorescence staining were performed. Long-term behavioral sequelae were evaluated by the rotarod and Morris water maze tests. Furthermore, OZ was added to the culture medium with oxyhemoglobin (OxyHb) to mimic SAH in vitro. The reactive oxygen species level was detected by DCFH-DA staining. Lysosomal integrity was assessed by Lyso-Tracker Red staining and Acridine Orange staining. Results The neuronal phosphorylated TAK1 expression was upregulated following SAH. Pharmacologic inhibition of TAK1 with OZ could alleviate neurological deficits, brain edema, and brain-blood barrier (BBB) disruption at 24 h after SAH. In addition, OZ administration restored long-term neurobehavioral function. Furthermore, blockade of TAK1 dampened neuronal pyroptosis by downregulating the N-terminal fragment of GSDMD (GSDMD-N) expression and IL-1β/IL-18 production. Mechanistically, both in vivo and in vitro, we demonstrated that TAK1 can induce neuronal pyroptosis through promoting nuclear translocation of NF-κB p65 and activating nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome. TAK1 siRNA treatment mitigated SAH-induced neurobehavioral deficits and restrained phosphorylated NF-κB p65 expression and NLRP3 inflammasome activation. TAK1 blockade also ameliorated reactive oxygen species (ROS) production and prevented lysosomal cathepsin B releasing into the cytoplasm. Conclusions Our findings demonstrate that TAK1 modulates NLRP3-mediated neuronal pyroptosis in EBI following SAH. Inhibition of TAK1 may serve as a potential candidate to relieve neuroinflammatory responses triggered by SAH.

Background Currently, limited research is available on the comparative analysis of chronic kidney disease (CKD) incidence and mortality rates between China and the United States. This study aimed to explore the trends in CKD incidence and mortality rates in both countries, as well as make some future predictions. Methods The data on CKD incidence and mortality in China and the US from 1990 to 2019 were derived from the 2019 Global Burden of Disease database. A Joinpoint regression model was used to analyze temporal trends in CKD incidence and mortality. An age-period-cohort model was used to assess the effects of age, period, and birth cohort on CKD risk and forecast the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of CKD in China and the US over the next 15 years. Results CKD incidence in China and the US showed an upward trend. Its mortality rate showed a downward trend in China but an upward one in the US. The relative risk (RR) of CKD incidence and mortality increases with age. The RR of CKD incidence in the 0–5 age group exceeds that in the 5–55 age group, and the RR for mortality surpasses that in the 5–35 age group. Over time, the RR of CKD incidence has gradually increased in China and the US. Individuals born in later birth cohorts had a lower RR of CKD incidence and mortality. The ASIR of CKD may increase in both China and the US, whereas its ASMR may decline over the next 15 years. Conclusion Screening measures should be strengthened among populations at high risk of CKD; prenatal examinations of pregnant women should be emphasized to reduce CKD incidence in newborns. It is imperative to increase health education and encourage individuals to adopt healthy lifestyles.

Anthocyanins are potential health-promoting compounds in the human diet. The atv (atroviolacium) locus, derived from the wild tomato species Solanum cheesmaniae, has been shown to enhance anthocyanin pigmentation in tomato fruit when it co-exists with either the Aft (Anthocyanin fruit) or the Abg (Aubergine) locus. In the present study, the atv locus was fine-mapped to an approximately 5.0-kb interval on chromosome 7. A putative R3 MYB repressor was identified in this interval and is hereby designated as SlMYBATV. The allele of SlMYBATV underlying the atv locus harbored a 4-bp insertion in its coding region, which is predicted to result in a frame-shift and premature protein truncation. The other candidate R3 MYB and R2R3 MYB repressors of anthocyanin biosynthesis were also identified in tomato via a genome-wide search. Transcriptional analysis showed that most of the structural genes and several regulatory genes of anthocyanin biosynthesis were up-regulated in the tomato SlMYBATV mutant lines. These findings may facilitate the elucidation of the molecular mechanisms underlying anthocyanin pigmentation in tomato fruit and help in the marker-assisted selection of anthocyanin-enriched tomato cultivars.

Large oilfields are often coincidentally located in major river deltas and wetlands, and potentially damage the structure, function and ecosystem service values of wetlands during oil exploration. In the present study, the effects of crude oil contamination during oil exploration on soil physical and chemical properties were investigated in marshes of the Momoge National Nature Reserve in Jilin Province, China. The concentrations of total petroleum hydrocarbons in the marsh soil near the oil wells are significantly higher than those in the adjacent control marsh. Soil water contents in oil-contaminated marshes are negatively correlated with soil temperature and are significantly lower than those in the control area, especially in fall. Crude oil contamination significantly increases the soil pH up to 8.0, and reduces available phosphorus concentrations in the soil. The concentrations of total organic carbon are significantly different among sampling sites. Therefore, crude oil contamination could potentially alkalinize marsh soils, adversely affect soil fertility and physical properties, and cause deterioration of the marshes in the Momoge National Nature Reserve. Phyto-remediation by planting Calamagrostis angustifolia has the potential to simultaneously restore and remediate the petroleum hydrocarbon-contaminated wetlands. Crude oil contamination affects the soil physical and chemical properties, so developing an effective restoration program in the Momoge wetland is neccesary.