Per1/Per2 double knockout transcriptome analysis reveals circadian regulation of hepatic lipid metabolism

Scope: Circadian disorder and high-fat diet(HFD)can disturb lipid metabolism homeostasis and may promote the development of various metabolic diseases. The relationship between them is of great concern. This study aimed to explore the effects of Per1/Per2 double knockout(DKO)on hepatic lipid metabolism in mice under HFD and HFD with docosahexaenoic acid(DHA)substitution. Methods and results: Both wild type(WT)and DKO male C57BL/6 mice were fed with normal chow diet(CON), HFD, or HFD with DHA substitution(AO)for 15 weeks. At the end of the experiment, mice were sacrificed at zeitgeber time(ZT)0(7:00 am)or ZT12(7:00 pm). Pathological indicators were determined using histological and biochemical methods. Hepatic transcriptome sequencing analysis showed that DKO mice exhibited multiple dysfunctions in diurnal rhythm, drug metabolism, cell cycle, cancer pathways, and lipid metabolism. HFD had greater effects on fatty acid oxidation and cholesterol synthesis and metabolism in Per1-/-Per2-/-mice, which was improved by DHA substitution. Conclusions: Per1/Per2 played an important role in the circadian regulation of hepatic lipid metabolism, and DKO mice were more sensitive to HFD. DHA can improve circadian-related lipid metabolism disruption induced by HFD in mice.

Application of Linearized Alternating Direction Multiplier Method in Dictionary Learning

The Alternating Direction Multiplier Method (ADMM) is widely used in various fields, and different variables are customized in the literature for different application scenarios [1] [2] [3] [4]. Among them, the linearized alternating direction multiplier method (LADMM) has received extensive attention because of its effectiveness and ease of implementation. This paper mainly discusses the application of ADMM in dictionary learning (non-convex problem). Many numerical experiments show that to achieve higher convergence accuracy, the convergence speed of ADMM is slower, especially near the optimal solution. Therefore, we introduce the linearized alternating direction multiplier method (LADMM) to accelerate the convergence speed of ADMM. Specifically, the problem is solved by linearizing the quadratic term of the subproblem, and the convergence of the algorithm is proved. Finally, there is a brief summary of the full text.

Environmental selection and evolutionary process jointly shape genomic and functional profiles of mangrove rhizosphere microbiomes

Mangrove reforestation with introduced species has been an important strategy to restore mangrove ecosystem functioning.However,how such activities affect microbially driven methane(CH4),nitrogen(N),and sulfur(S)cycling of rhizosphere microbiomes remains unclear.To understand the effect of environmental selection and the evolutionary process on microbially driven biogeochemical cycles in native and introduced mangrove rhizospheres,we analyzed key genomic and functional profiles of rhizosphere microbiomes from native and introduced mangrove species by metagenome sequencing technologies.Compared with the native mangrove(Kandelia obovata,KO),the introduced mangrove(Sonneratia apetala,SA)rhizosphere microbiome had significantly(p<0.05)higher average genome size(AGS)(5.8 vs.5.5 Mb),average 16S ribosomal RNA gene copy number(3.5 vs.3.1),relative abundances of mobile genetic elements,and functional diversity in terms of the Shannon index(7.88 vs.7.84)but lower functional potentials involved in CH4 cycling(e.g.,mcrABCDG and pmoABC),N2 fixation(nifHDK),and inorganic S cycling(dsrAB,dsrC,dsrMKJOP,soxB,sqr,and fccAB).Similar results were also observed from the recovered Proteobacterial metagenome-assembled genomes with a higher AGS and distinct functions in the introduced mangrove rhizosphere.Additionally,salinity and ammonium were identified as the main environmental drivers of functional profiles of mangrove rhizosphere microbiomes through deterministic processes.This study advances our understanding of microbially mediated biogeochemical cycling of CH_(4),N,and S in the mangrove rhizosphere and provides novel insights into the influence of environmental selection and evolutionary processes on ecosystem functions,which has important implications for future mangrove reforestation.

Microbially Driven Sulfur Cycling in the River–Wetland–Ocean Continuum

Sulfur(S)is an essential biological element,and S cycling is mainly driven by metabolically versatile microorganisms.The river–wetland–ocean(RWO)continuum here is defined as the dynamically connected region with estuary,wetland,and near-marine ecosystems,and it is considered a hotspot of biogeochemical cycling,especially a major biotope for S cycling.Various forms and oxidation states of S compounds are considered ideal electron donors or acceptors and are widely utilized by microorganisms via inorganic or organic S-cycling processes.The S-cycling pathways are intimately linked to the carbon(C),nitrogen,phosphorus,and metal cycles,playing crucial roles in biogeochemical cycling,C sequestration,and greenhouse gas emissions through various mechanisms in the RWO continuum.This review provides a comprehensive understanding of microbially driven S cycling in the RWO continuum.We first illustrate the importance of S cycling in this continuum,including key microorganisms and functional processes(e.g.,dissimilatory sulfate reduction,S oxidation,dimethylsulfoniopropionate production,and catabolism)as well as their corresponding S flux characteristics.In particular,we emphasize recent advances in the coupling mechanisms of the S cycle with other major element cycles.We further propose important perspectives for developing microbiome engineering of S-cycling microbial communities via integration of current knowledge about the multidimensional diversity,cultivation,evolution,and interaction of S-cycling microorganisms and their coupling mechanisms in the RWO continuum,providing a new window on applying microbiome-based biotechnologies to overcome global climate challenges.

Risk factors for early-onset colorectal cancer:A large-scale Chinese cohort study

Background:The incidence of early-onset colorectal cancer(EOCRC)has increased globally since the early 1990s.Comprehensively examining the risk factors would be helpful for risk stratification and the development of per-sonalized colorectal cancer screening strategies.Methods:We performed a prospective study of the Chinese population aged 30-50 years to identify potential risk factors during a median follow-up of 9.1 years.We compared the distribution of demographic characteris-tics,lifestyle factors,dietary habits,and medical history among 222 EOCRC cases and 87,833 normal controls.Multivariate adjusted Cox hazard models were used for estimating EOCRC risks of each risk factor.Results:Our final analyses indicated that participants with a higher body mass index(HR,1.04;95%CI:1.00,1.08),regular alcohol consumption(HR,1.69;95%CI:1.12,2.91),higher intake of fish(HR,1.64;95%CI:1.01,2.67),hypertension(HR,1.99;95%CI:1.04,3.81),diabetes(HR,2.20;95%CI:1.08,4.49),and first-degree relatives with cancer(HR,1.70;95%CI:1.23,2.36)were at higher risk of EOCRC.Conclusion:We identified several modifiable as well as nonmodifiable risk factors,such as higher BMI,alcohol and fish consumption,hypertension,and diabetes,were associated with EOCRC.

Analysis of a 1 kW organic Rankine cycle using a scroll expander for engine coolant and exhaust heat recovery

The development of engine waste heat recov- ery technologies attracts ever increasing interests due to the rising strict policy requirements and environmental con- cerns. This paper presented the study of engine coolant and exhaust heat recovery using organic Rankine cycle （ORC）. Eight working fluids were selected to evaluate and compare the performance of the integrated waste heat recovery system. Rather than the conventional engine ORC system mainly focusing on the utilization of exhaust energy, this work proposed to fully use the engine coolant energy by changing the designed parameters of the ORC system. The case study selected a small engine as the heat source to drive the ORC system using a scroll expander for power production. The evaluation results suggest that under the engine rated condition, the solution to fully recover the engine coolant energy can achieve a higher power generation performance than that of the conven- tional engine ORC system. The results suggest that adding a recuperator to the ORC system can potentially improve the system performance when the working fluids are dry and the overall dumped heat demand of the system can be reduced by 12% under optimal conditions. When the ORC evaporating and condensing temperature are respectivelyset at 85℃ and 30℃, the integrated engine waste heat recovery system can improve the overall system efficiency by 9.3% with R600, R600a or n-Pentane as the working fluid.

CACA Guidelines for Holistic Integrative Management of Breast Cancer

Purpose:Breast cancer is now the most common malignant tumor worldwide.About one-fourth of female cancer patients all over the world sufer from breast cancer.And about one in six female cancer deaths worldwide is caused by breast cancer.In terms of absolute numbers of cases and deaths,China ranks frst in the world.The CACA Guidelines for Holistic Integrative Management of Breast Cancer were edited to help improve the diagnosis and comprehensive treatment in China.Methods:The Grading of Recommendations Assessment,Development and Evaluation(GRADE)was used to classify evidence and consensus.Results:The CACA Guidelines for Holistic Integrative Management of Breast Cancer include the epidemiology of breast cancer,breast cancer screening,breast cancer diagnosis,early breast cancer treatment,advanced breast cancer treatment,follow-up,rehabilitation,and traditional Chinese medicine treatment of breast cancer patients.Conclusion:We to standardize the diagnosis and treatment of breast cancer in China through the formulation of the CACA Guidelines.

Metagenomic insights into the effects of submerged plants on functional potential of microbial communities in wetland sediments

Submerged plants in wetlands play important roles as ecosystem engineers to improve self-purification and promote elemental cycling.However,their effects on the functional capacity of microbial communities in wetland sediments remain poorly understood.Here,we provide detailed metagenomic insights into the biogeochemical potential of microbial communities in wetland sediments with and without submerged plants(i.e.,Vallisneria natans).A large number of functional genes involved in carbon(C),nitrogen(N)and sulfur(S)cycling were detected in the wetland sediments.However,most functional genes showed higher abundance in sediments with submerged plants than in those without plants.Based on the comparison of annotated functional genes in the N and S cycling databases(i.e.,NCycDB and SCycDB),we found that genes involved in nitrogen fixation(e.g.,nifD/H/K/W),assimilatory nitrate reduction(e.g.,nasA and nirA),denitrification(e.g.,nirK/S and nosZ),assimilatory sulfate reduction(e.g.,cysD/H/J/N/Q and sir),and sulfur oxidation(e.g.,glpE,soeA,sqr and sseA)were significantly higher(correctedp<0.05)in vegetated vs.unvegetated sediments.This could be mainly driven by environmental factors including total phosphorus,total nitrogen,and C:N ratio.The binning of metagenomes further revealed that some archaeal taxa could have the potential of methane metabolism including hydrogenotrophic,acetoclastic,and methylotrophic methanogenesis,which are crucial to the wetland methane budget and carbon cycling.This study opens a new avenue for linking submerged plants with microbial functions,and has further implications for understanding global carbon,nitrogen and sulfur cycling in wetland ecosystems.

A three-parameter logistic regression model

Dose–response experiments and data analyses are often carried out according to an optimal design under a model assumption.A two-parameter logistic model is often used because of its nice mathematical properties and plausible stochastic response mechanisms.There is an extensive literature on its optimal designs and data analysis strategies.However,a model is at best a good approximation in a real-world application,and researchers must be aware of the risk of model mis-specification.In this paper,we investigate the effectiveness of the sequential EDdesign,the D-optimal design,and the up-and-down design under the three-parameter logistic regression model,and we develop a numerical method for the parameter estimation.Simulations show that the combination of the proposed model and the data analysis strategy performs well.When the logistic model is correct,this more complex model has hardly any efficiency loss.The three-parameter logistic model works better than the two-parameter logistic model in the presence of model mis-specification.

Involvement of GluA1-AMPAR-mediated LTP in time-dependent decline of cognitive function in rats with temporal lobe epilepsy

Background:Cognitive impairment is one of the common comorbidities in patients with temporal lobe epilepsy(TLE),but the underlying mechanisms remain largely unknown.Previous studies have found significant decay of hippocampal long-term potentiation(LTP)in TLE rats with cognitive impairment.As the activation ofα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors(AMPARs)is responsible for LTP formation and learning and memory,we investigated whether AMPARs are involved in the LTP inhibition and the TLE-associated cognitive impairments.Methods:TLE rat model was established by intraperitoneal injection of lithium chloride-pilocarpine on postnatal day 21(P21).Learning and memory performance,hippocampal expression of membrane GluA1-AMPARs,and hippocampal LTP were tested by behavioral tests,western blotting,and field potential recording,respectively,at 1,5 and 13 weeks after induction of status epilepticu(SE).Finally,the effects of(S)-AMPA,an agonist of AMPARs,on LTP and cognitive function were tested.Results:Results of behavioral tests revealed an time-dependent decline in the learning and memory of TLE rats when compared to the age-matched controls at week 5 and 13,rather than at week 1 after the induction of SE.Western blotting showed that the hippocampal expression of membrane GluA1 was significantly decreased in a time-dependent manner in the TLE rats when compared to the age-matched controls at weeks 5 and 13,rather than at week 1 after the induction of SE.Similarly,the hippocampal LTP was inhibited in a time-dependent manner in TLE rats at weeks 5 and 13,rather than at week 1 after the induction of SE.Moreover,intra-hippocampal injection of(S)-AMPA ameliorated the deficits in learning as well as spatial and emotional memory in a dosedependent manner,and partially reversed the inhibition of CA1 LTP in the TLE rats at week 13 after the induction of SE.Conclusions:The reduced expression of hippocampal membrane GluA1 may be involved in LTP decay in CA1 and cognition impairment in TLE rats.