Transcriptomic and metabolomic analysis of the effects of Zhenwu decoction on kidney yang deficiency pattern in chronic kidney disease

Objective:To explore the kidney yang deficiency pattern(KYDP)in a chronic kidney disease(CKD)rat model and the mechanisms underlying the effects of Zhenwu decoction(ZWD)by conducting tran-scriptomic and metabolomic analyses.Methods:Adriamycin(ADR)combined with hydrocortisone(HC)was used to induce CKD with KYDP in rats.ADR was injected into the tail vein twice.HC was injected intramuscularly for 8 weeks.ZWD was administered by gavage for 8 weeks.The general condition was observed,24-h urine protein was detected,serum corticosterone,triiodothyronine,thyroxine,TSH,testosterone,cAMP,and cGMP levels were determined,and pathological analysis was conducted.Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes(DEGs),differentially expressed metabolites(DEMs),and differentially expressed pathways(DEPs).The core DEMs and DEGs were input to Metab-oanalyst 5.0 to identify the pathways affected by ZWD.Results:In the HC group,KYDP symptoms were observed.Compared with control group,the levels of 24-h urine protein,TSH,and cGMP significantly increased(all P<0.01),and corticosterone,triiodothyronine,thyroxine,and cAMP significantly decreased(all P<0.01)in the HC group.After ZWD intervention,the levels of above-mentioned indicators could be reversed to some extent.Pathological analysis in the HC group revealed kidney lesions.DEGs in the ZWD group were mainly associated with pathways such as nucleotide synthesis and endocrine pathways.In the ZWD group,differences in biosynthesis of unsat-urated fatty acids and butanoate metabolism were observed.The following pathways were significantly affected by ZWD:arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.Conclusion:ZWD can be used to treat KYDP in CKD through regulating arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.

Single-atom photo-catalysts:Synthesis,characterization,and applications

Single-atom catalysts(SACs)are gaining popularity in catalytic reactions due to their nearly 100%atomic utilization and defined active sites,which provide great convenience for studying the catalytic mechanism of catalysts.However,SACs still present challenges such as complex formation processes,low loading and easy agglomeration of catalysts.Herein,we systematically discuss the synthesis methods for SACs,including coprecipitation,impregnation,atomic layer deposition,pyrolysis and Anti-Ostwald ripening etc.Various techniques for characterizing single-atom catalysts(SACs)are described in detail.The utilization of individual atoms in various photocatalytic reactions and their mechanisms of action in different reactions are explained.The purpose of this review is to introduce single-atom synthesis methods,characterization techniques,specific catalytic action and their applications in the direction of photocatalysis,and to provide a reference for the industrialization of photocatalytic single-atoms,which is currently impossible,in the hope of promoting further development of photocatalytic single-atoms.

Differentially Private Real-Time Streaming Data Publication Based on Sliding Window Under Exponential Decay

Continuous response of range query on steaming data provides useful information for many practical applications as well as the risk of privacy disclosure.The existing research on differential privacy streaming data publication mostly pay close attention to boosting query accuracy,but pay less attention to query efficiency,and ignore the effect of timeliness on data weight.In this paper,we propose an effective algorithm of differential privacy streaming data publication under exponential decay mode.Firstly,by introducing the Fenwick tree to divide and reorganize data items in the stream,we achieve a constant time complexity for inserting a new item and getting the prefix sum.Meanwhile,we achieve time complicity linear to the number of data item for building a tree.After that,we use the advantage of matrix mechanism to deal with relevant queries and reduce the global sensitivity.In addition,we choose proper diagonal matrix further improve the range query accuracy.Finally,considering about exponential decay,every data item is weighted by the decay factor.By putting the Fenwick tree and matrix optimization together,we present complete algorithm for differentiate private real-time streaming data publication.The experiment is designed to compare the algorithm in this paper with similar algorithms for streaming data release in exponential decay.Experimental results show that the algorithm in this paper effectively improve the query efficiency while ensuring the quality of the query.

FGF-receptor substrate 2 functions as a molecular sensor ntegrating external regulatory signals into the FGF pathway

Fibroblast growth factor （FGF） receptor substrate 2a （FRS2α） is the main mediator of signaling in the FGF pathway. Recent studies have shown that mitogen-activated protein kinase （MAPK） phosphorylates serine and threonine residues in FRS2, negatively affecting FGF-induced tyrosine phosphorylation （PY） of FRS2. Several kinds of stimuli can induce serine/threonine phosphorylation （PS/T） of FRS2, indicating that FRS2 may be useful for studying crosstalk between growth factor signaling pathways. Here, we report that FGF-induced PY of FRS2 can be attenuated by EGF co-stimulation in PC12cells; this inhibitory effect could be completely reversed by U0126, an inhibitor of MEK. We further identified the ERK1/2-binding motif in FRS2 and generated FRS2-3KL, a mutant lacking MAPK binding and PT upon FGF and/or EGF stimulation. Unlike wild-type （WT） FRS2, FGF-induced PY of FRS2-3KL could not be inhibited by EGF co-stimulation, and FRS2-3KL-expressing PC12 cells exhibited more differentiating potential than FRS2-WT-expressing cells in response to FGF treatment. These results suggest that PS/T of FRS2 mediated by the FRS2-MAPK negative regulatory loop may function as a molecular switch integrating negative regulatory signals from other pathways into FGFR-generated signal transduction.

An Optimal Algorithm for Prufer Codes

This paper studies the algorithms for coding and decoding Prufer codes of a labeled tree. The algorithms for coding and decoding Prufer codes of a labeled tree in the literatures require time usually. Although there exist linear time algorithms for Prufer-like codes [1,2,3], the algorithms utilize the integer sorting algorithms. The special range of the integers to be sorted is utilized to obtain a linear time integer sorting algorithm. The Prufer code problem is reduced to integer sorting. In this paper we consider the Prufer code problem in a different angle and a more direct manner. We start from a na&#239;ve algorithm, then improved it gradually and finally we obtain a very practical linear time algorithm. The techniques we used in this paper are of interest in their own right.

Bioinspired zinc-mediated umpolung thiolation of alkyl electrophiles: reaction development, scope and mechanism

Zinc-promoted umpolung thiolation of alkyl electrophiles with masked sulfur transfer reagents in the absence of nickel or copper catalysis is described. This protocol proceeds via a SET process of Zn to electrophilic sulfur reagent followed by insertion of Zn into disulfide and nucleophilic thiolation, providing straightforward access to a wide range of alkyl sulfides with broad substrate scope. A neutral TMEDA-ligated four-coordinated zinc thiolate with tetrahedra geometry was synthesized, isolated and fully characterized by NMR, IR and X-ray analysis. More importantly, the chemical reactivity of this active intermediate has been investigated, enabling the construction of C-Se, C-Te, Sb-S and Bi-S bonds to prepare valuable sulfur-containing molecules and beyond.

A soft-contact hybrid electromagnetic–triboelectric nanogenerator for self-powered water splitting towards hydrogen production

The effective acquisition of hydrogen energy from the ocean offers a promising sustainable solution for increasing global energy shortage.Herein,a self-powered high-efficient hydrogen generation system is proposed by integrating a triboelectric–electromagnetic hybrid nanogenerator(TEHG),power management circuit(PMC),and an electrolytic cell.Under the wind triggering,as-fabricated TEHG can effectively convert breeze energy into electric energy,which demonstrates a high output current of 20.3 mA at a speed rotation of 700 rpm and the maximal output power of 13.8 mW at a load of 10 MΩ.Remarkably,asdesigned self-powered system can perform a steady and continuous water splitting to produce hydrogen(1.5μL·min^(−1))by adding a matching capacitor between the PMC and electrolytic cell.In the circuit,the capacitor can not only function as a charge compensation source for water splitting,but also stabilize the working voltage.Unlike other self-powered water splitting systems,the proposed system does not need catalysts or the complex electrical energy storage/release process,thus improving the hydrogen production efficiency and reducing the cost.This work provides an effective strategy for clean hydrogen energy production and demonstrates the huge potential of the constructed self-powered system toward carbon neutralization.

胶体马达

胶体马达亦称微纳米马达、微纳米泳体或游动纳米机器人,是研究复杂系统的绝佳非平衡态物理模型,同时因其具有额外的自推进力、自主导航等独特优势,有望为靶向药物递送等生物医学应用带来颠覆性变革.作为一个新兴的多学科交叉领域,胶体马达拓展了胶体与界面化学的研究范畴,带来了新的现象、理论与应用,是以胶体科学为核心的国际前沿交叉学科研究的热点领域.本文系统地阐述了胶体马达以及基于胶体马达的超分子胶体马达和游动纳米机器人的新概念,同时以本课题组在胶体马达领域取得的研究成果为例,详细综述了胶体马达的结构设计与可控制备、驱动机理及运动行为的界面调控策略、集群行为规律与重构方法以及突破各种生物屏障实现药物主动靶向递送等方面的最新进展,在此基础上展望了胶体马达对于胶体科学发展所带来的新机遇与新挑战.

Inhibiting ceramide synthase 5 expression in microglia decreases neuroinflammation after spinal cord injury

Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord injury.However,the precise mechanism remains unclear.To investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial subpopulations.We found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high levels.Subsequently,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord injury.Finally,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron cells.Inhibiting ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced pyroptosis.Furthermore,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling pathway.Inhibiting ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological function.Pla2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling pathway.Collectively,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.

Near-infrared light-driven Janus capsule motors： Fabrication, propulsion, and simulation

We report a fuel-free, near-infrared （NIR）-driven Janus microcapsule motor. The Janus microcapsule motors were fabricated by template-assisted polyelectrolyte layer-by-layer assembly, followed by spraying of a gold layer on one side. The NIR-powered Janus motors achieved high propulsion with a maximum speed of 42μm.s-1 in water. The propulsion mechanism of the Janus motor was attributed to the self-thermophoresis effect： The asymmetric distribution of the gold layer generated a local thermal gradient, which in turn generated thermophoretic force to propel the Janus motor. Such NIR-propelled Janus capsule motors can move efficiently in cell culture medium and have no obvious effects on the cell at the power of the NIR laser, indicating considerable promise for future biomedical applications.

Chromosome doubling of Sedum alfredii Hance: A novel approach for improving phytoremediation efficiency

Sedum alfredii Hance is a cadmium(Cd)/zinc(Zn)hyperaccumulator native to China.However,its relatively low biomass restricted the large-scale application for heavy metal contamination remediation.The chromosome set doubling of S.alfredii in vitro was achieved by 0.1%–0.2%(W/V)colchicine treatment.The plant DNA ploidy was analyzed by flow cytometry and chromosome set doubling plants(CSD)were identified based on the obvious different sharp peak.A tissue culture experiment with different Cd treated levels and a field trial with natural polluted mined soil were conducted to study the effects of chromosome doubling on plant biomass and Cd accumulation in shoots.The results suggested that S.alfredii is a mixoploid.Compared with the wild type plants(WT),CSD exhibited typical"gigas"characteristics in morphology including stem thickness,root hair production,number of leaves and size of stoma guard cell.Fresh weight and dry weight of CSD were increased to 1.62–2.03-fold and 2.26–3.25-fold of WT.And Cd content of CSD showed a17.49%–42.82%increase and 59%increase under tissue culture and field condition,accordingly.In addition,the TF and in BCF of CSD were 2.37-and 1.59-fold of WT,respectively.These results proved that it is feasible to promote phytoextraction efficiency of S.alfredii in Cd contaminated soils through chromosomal engineering,which provides a novel approach for hyperaccumulator application in phytoremediation.

The S100 calcium binding protein A11 promotes liver fibrogenesis by targeting TGF-βsignaling

Liver fibrosis is a key transformation stage and also a reversible pathological process in various types of chronic liver diseases.However,the pathogenesis of liver fibrosis still remains elusive.Here,we report that the calcium binding protein A11(S100A11)is consistently upregulated in the integrated data from GSE liver fibrosis and tree shrew liver proteomics.S100A11 is also experimentally activated in liver fibrosis in mouse,rat,tree shrew,and human with liver fibrosis.While overexpression of S100A11 in vivo and in vitro exacerbates liver fibrosis,the inhibition of S100A11 improves liver fibrosis.Mechanistically,S100A11 activates hepatic stellate cells(HSCs)and the fibrogenesis process via the regulation of the deacetylation of Smad3 in the TGF-βsignaling pathway.S100A11 physically interacts with SIRT6,a deacetylase of Smad2/3,which may competitively inhibit the interaction between SIRT6 and Smad2/3.The subsequent release and activation of Smad2/3 promote the activation of HSCs and fibrogenesis.Additionally,a significant elevation of S100A11 in serum is observed in clinical patients.Our study uncovers S100A11 as a novel profibrogenic factor in liver fibrosis,which may represent both a potential biomarker and a promising therapy target for treating liver fibrosis and fibrosis-related liver diseases.

Functionalized gadofullerene ameliorates impaired glycolipid metabolism in type 2 diabetic mice

The soaring global prevalence of diabetes makes it urgent to explore new drugs with high efficacy and safety.Nanomaterial-derived bioactive agents are emerging as one of the most promising candidates for biomedical application.In the present study,we investigated the anti-diabetic effects of a functionalized gadofullerene(GF)using obese db/db and non-obese mouse model of type 2 diabete mellitus(MKR)mouse type 2 diabetes mellitus(T2DM)models.In both mouse models,the diabetic phenotypes,including hyperglycemia,impaired glucose tolerance,and insulin sensitivity,were ameliorated after two or four weeks of intraperitoneal administration of GF.GF lowered blood glucose levels in a dose-dependent manner.Importantly,the restored blood glucose levels could persist ten days after withdrawal of GF treatment.The hepatic AKT/GSK3β/FoxO1 pathway is shown to be the main target of GF for rebalancing gluconeogenesis and glycogen synthesis in vivo and in vitro.Furthermore,GF treatment significantly reduced weight gain of db/db mice with reduced hepatic fat storage by the inhibition of de novo lipogenesis through m TOR/S6K/SREBP1 pathway.Our data provide compelling evidence to support the promising application of GF for the treatment of T2DM.