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Biosynthesis of trialkyl-substituted aromatic polyketide NFAT-133 involves unusual P450 monooxygenase-mediating aromatization and a putative metallo-beta-lactamase fold hydrolase

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Synthetic and Systems Biotechnology 2023年第3期8卷 349-356页

作者： Ming Yang Wanlu Li lin Zhou Xiao lin Wenyu Zhang Yaoyao Shen Hai Deng Hou-wen lin Yongjun zhou Research Center for Marine Drugs Department of PharmacyRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China Institute of Marine Drugs Guangxi Key Laboratory of Marine DrugsGuangxi University of Chinese MedicineNanning530200PR China Department of Chemistry University of AberdeenAberdeenAB243UEUK

The bacterial trialkyl-substituted aromatic polyketides are structurally featured with the unusual aromatic core in the middle of polyketide chain such as TM-123(1),veramycin A(2),NFAT-133(3)and benwamycin I(4),which were discovered from Streptomyces species and demonstrated with antidiabetic and immunosuppressant activities.Though the biosynthetic pathway of 1-3 was reported as a type I polyketide synthase(PKS),the PKS assembly line was interpreted inconsistently,and it remains a mystery how the compound 3 was generated.Herein,the PKS assembly logic of 1-4 was revised by site-mutagenetic analysis of the PKS dehydratase domains.Based on gene deletion and complementation,the putative P450 monooxygenase nftE1 and metallo-beta-lactamase(MBL)fold hydrolase nftF1 were verified as essential genes for the biosynthesis of 1-4.The absence of nftE1 led to abolishment of 1-4 and accumulation of new products(5-8).Structural elucidation reveals 5-8 as the non-aromatic analogs of 1,suggesting the NftE1-catalyzed aromatic core formation.Deletion of nftF1 resulted in disappearance of 3 and 4 with the compounds 1 and 2 unaffected.As a rare MBL-fold hydrolase from type I PKSs,NftF1 potentially generates the compound 3 through two strategies:catalyze premature chain-offloading as a trans-acting thioesterase or hydrolyze the lactone-bond of compound 1 as an esterase.

关键词： Thioesterase Metallo hydrolase Metallo-beta-lactamase Aromatic polyketide Polyketide synthase P450 monooxygenase

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Deep learning-based local climate zone classification using Sentinel-1 SAR and Sentinel-2 multispectral imagery

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Geo-Spatial Information Science 2022年第3期25卷 383-398页

作者： lin Zhou Zhenfeng Shao Shugen Wang Xiao Huang School of Remote Sensing and Information Engineering Wuhan UniversityWuhanChina State Key Laboratory of Information Engineering in Surveying Mapping and Remote SensingWuhan UniversityWuhanChina Department of Geosciences University of ArkansasFayettevilleNCUSA

As a newly developed classification system,the LCZ scheme provides a research framework for Urban Heat Island(UHI)studies and standardizes the worldwide urban temperature observa-tions.With the growing popularity of deep learning,deep learning-based approaches have shown great potential in LCZ mapping.Three major cities in China are selected as the study areas.In this study,we design a deep convolutional neural network architecture,named Residual combined Squeeze-and-Excitation and Non-local Network(RSNNet),that consists of the Squeeze-and-Excitation(SE)block and non-local block to classify LCZ using freely available Sentinel-1 SAR and Sentinel-2 multispectral imagery.Overall Accuracy(OA)of 0.9202,0.9524 and 0.9004 for three selected cities are obtained by applying RSNNet and training data of individual city,and OA of 0.9328 is obtained by training RSNNet with data from all three *** outperforms other popular Convolutional Neural Networks(CNNs)in terms of LCZ mapping accuracy.We further design a series of experiments to investigate the effect of different characteristics of Sentinel-1 SAR data on the performance of RSNNet in LCZ mapping.The results suggest that the combination of SAR and multispectral data can improve the accuracy of LCZ classification.The proposed RSNNet achieves an OA of 0.9425 when integrat-ing the three decomposed components with Sentinel-2 multispectral images,2.44%higher than using Sentinel-2 images alone.

关键词： Local Climate Zone(LCZ) deep learning Sentinel-1 Sentinel-2

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Integration of stereotactic radiosurgery or whole brain radiation therapy with immunotherapy for treatment of brain metastases

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Chinese Journal of Cancer Research 2020年第4期32卷 448-466页

作者： zhou Su lin Zhou Jianxin Xue You Lu Department of Thoracic Oncology Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Department of Oncology Sichuan Mianyang 404 HospitalMianyang 621000China

The prognosis of brain metastases(BM)is traditionally poor.BM are mainly treated by local radiotherapy,including stereotactic radiosurgery(SRS)or whole brain radiation therapy(WBRT).Recently,immunotherapy(i.e.,immune checkpoint inhibitors,ICI)has demonstrated a survival advantage in multiple malignancies commonly associated with BM.Individually,radiotherapy and ICI both treat BM efficiently;hence,their combination seems logical.In this review,we summarize the existing preclinical and clinical evidence that supports the applicability of radiotherapy as a sensitizer of ICI for BM.Further,we discuss the optimal timing at which radiotherapy and ICI should be administered and review the safety of the combination therapy.Data from a few clinical studies suggest that combining SRS or WBRT with ICI simultaneously rather than consecutively potentially enhances brain abscopal-like responses and survival.However,there is a lack of conclusion about the definition of"simultaneous";the cumulative toxic effect of the combined therapies also requires further study.Thus,ongoing and planned prospective trials are needed to further explore and validate the effect,safety,and optimal timing of the combination of immunotherapy with radiotherapy for patients with BM.

关键词： Immunotherapy radiotherapy immune checkpoint inhibitors brain metastases review

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Transcriptome-based identification and expression analysis of the glutathione S-transferase(GST)family in tree peony reveals a likely role in anthocyanin transport

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Horticultural Plant Journal 2022年第6期8卷 787-802页

作者： Lulu Han Hongzhu Zou lin Zhou Yan Wang Research Institute of Forestry Key Laboratory of Tree Breeding and Cultivation of National Forestry and Grassland AdministrationChinese Academy of ForestryBeijing 100091China

For red-flowered cultivars of tree peony(Paeonia suffruticosa),anthocyanin content is a critical factor determining the different petal pigmentations.Glutathione S-transferases(GSTs)are ubiquitous and multifunctional conjugating proteins that may be responsible for the transport of anthocyanin pigments from the cytoplasm to vacuole.The underlying function of the GST family in tree peony,however,remains unclear.In this study,we systematically isolated and identified a total of 54 putative full-length Ps GST genes through a combination of bioinformatics approaches from transcriptome databases.Intraspecific phylogenetic analyses revealed extensive differentiation in their coding sequences and divided them into 10 of the 14 known classes of plant GSTs.The phylogenetic relationships,evolutionary characteristics,protein domain,and motif organization were clearly conserved among the different phylogenetic subclasses.The results of the RNA-seq and quantitative real-time polymerase chain reaction experiments exhibited extensive variation in gene expression profiles among different developmental stages and varieties.Furthermore,the phylogenetic relationships,expression profiles,protein interactions,weighted gene co-expression network analysis,and correlation analysis results suggested that PsGSTF3(Unigene 0064200)is a candidate participant in anthocyanin transport and the promotion of pigment accumulation,exhibiting a strong positive correlation with anthocyanin content among different tissues(r=0.908**)and an increasing rate of anthocyanin content during the flower developmental process(r=0.961*).These results furthered our understanding of the transport and accumulation functions of the GST family as well as the enhancement of tree peony breeding through molecular biology techniques.

关键词： GST Paeonia suffruticosa Functional prediction Expression analysis Anthocyanin transportation

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Malondialdehyde levels in diabetic retinopathy patients:a systematic review and meta-analysis

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Chinese Medical Journal 2023年第11期136卷 1311-1321页

作者： Fanwen Jiang lin Zhou Chun Zhang Hui Jiang Zhuping Xu Department of Ophthalmology West China HospitalSichuan UniversityChengduSichuan 610041China

Background:It remains unclear whether circulating malondialdehyde(MDA)levels change in people with diabetic retinopathy(DR).This systematic review compared circulating MDA levels in diabetic people with and without DR.Methods:PubMed,Medline(Ovid),Embase(Ovid),and Web of Science were searched for case-control studies conducted before May 2022 in English that compared circulating MDA levels in people with and without DR.The following MeSH search terms were used:("malondialdehyde"or"thiobarbituric acid reactive substances[TBARS]"or"lipid peroxidation"or"oxidative stress")and"diabetic retinopathy."Newcastle-Ottawa Quality Assessment Scale was used to evaluate the quality of the included studies.Random-effects pairwise meta-analysis pooled the effect size with standardized mean difference(SMD)and 95%confidence intervals(CIs).Results:This meta-analysis included 29 case-control studies with 1680 people with DR and 1799 people with diabetes but not DR.Compared to people without DR,the circulating MDA levels were higher in those with DR(SMD,0.897;95%CI,0.631 to 1.162;P<0.001).The study did not identify credible subgroup effects or publication bias and the sensitivity analysis confirmed the robustness of the study.Conclusions:Circulating MDA levels are higher in people with DR compared to those without.Future comparative studies that use more specific methods are required to draw firm conclusions.Registration:PROSPERO;https://www.***.york.***.uk/PROSPERO/;No.CRD42022352640.

关键词： Malondialdehyde Diabetic retinopathy Lipid peroxidation Oxidative stress

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Risk-averse Contextual Multi-armed Bandit Problem with linear Payoffs

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Journal of Systems Science and Systems Engineering 2023年第3期32卷 267-288页

作者： Yifan lin Yuhao Wang Enlu zhou School of Industrial and Systems Engineering Georgia Institute of TechnologyAtlantaGAUSA

In this paper we consider the contextual multi-armed bandit problem for linear payoffs under a risk-averse criterion.At each round,contexts are revealed for each arm,and the decision maker chooses one arm to pull and receives the corresponding reward.In particular,we consider mean-variance as the risk criterion,and the best arm is the one with the largest mean-variance reward.We apply the Thompson sampling algorithm for the disjoint model,and provide a comprehensive regret analysis for a variant of the proposed algorithm.For T rounds,K actions,and d-dimensional feature vectors,we prove a regret bound of O((1+ρ+1/ρ)d In T ln K/δ√dKT^(1+2∈)ln K/δ1/e)that holds with probability 1-δunder the mean-variance criterion with risk tolerance p,for any 0<ε<1/2,0<δ<1.The empirical performance of our proposed algorithms is demonstrated via a portfolio selection problem.

关键词： Multi-armed bandit context risk-averse Thompson sampling

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Conductive polymer hydrogel-coated nanopipette sensor with tunable size

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Nanotechnology and Precision Engineering 2022年第4期5卷 18-25页

作者： lin Li Feng zhou Qiannan Xue State Key Laboratory of Precision Measuring Technology and Instruments Tianjin UniversityTianjin 300072China College of Precision Instruments and Optoelectronics Engineering Tianjin UniversityTianjin 300072China

Nanopipette-based sensors are one of the most effective tools for detecting nanoparticles,bioparticles,and biomolecules.Quantitative analysis of nanoparticles with different shapes and electrical charges is achieved through measurement of the blockage currents that occur when particles pass through the nanopore.However,typical nanopipette sensors fabricated using a conventional needle-pulling method have a typical pore-diameter limitation of around 100 nm.Herein,we report a novel conductive hydrogel-composited nanopipette sensor with a tunable inner-pore diameter.This is made by electrodepositing poly(3,4-ethylenedioxythiophene)polystyrene sulfonate onto the surface of a nanopipette with a prefabricated sacrificial copper layer.Because of the presence of copper ions,the conductive polymer can stably adhere to the tip of the nanopipette to form a nanopore;when nanoparticles pass through the conductive nanopore,more distinct blocking events are observed.The size of the nanopore can be changed simply by adjusting the electrodeposition time.In this way,suitable nanopores can be obtained for highly sensitive screening of a series of particles with diameters of the order of tens of nanometers.

关键词： Nanopipette Conductive polymer Electrodeposition Nanoparticles

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Systematic diesel molecular performance evaluation based on quantitative structure-property relationship model

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Petroleum Science 2022年第2期19卷 809-818页

作者： Guang-Qing Cai lin-zhou Zhang State Key Laboratory of Heavy Oil Processing Petroleum Molecular Engineering Center(PMEC)China University of PetroleumBeijing 102249China

The production and separation of optimal molecules in diesel fuels require a systematic property evaluation for the containing molecules.This paper evaluates the diesel molecules based on four key quality indicators:low-temperature fluidity,cleanliness,ignition,and power performance.We established the corresponding quantitative structure-property relationship models for corresponding properties,which are freezing point,yield sooting index,cetane number,and combustion heat.The models were applied for the screening of the high-performance molecules that is suitable for diesel.The molecular performance distribution of the conventional diesel and biodiesel were also compared.Moreover,we analyzed the effect of different transformation paths on molecular properties,giving guidance on the conversion process design.

关键词： Diesel Optimal molecules QSPR Molecular screening

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Phase regimes of parity-time-symmetric coupled-ring systems at exceptional points

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Photonics Research 2022年第10期10卷 2374-2379页

作者： ZHUANG MA XIAOYAN zhou lin ZHANG Tianjin Key Laboratory of Integrated Opto-electronics Technologies and Devices School of Precision Instruments and Opto-electronics EngineeringTianjin UniversityTianjin 300072China Peng Cheng Laboratory Shenzhen 518038China

The optical coupled resonant system consisting of an integrated resonator with gain and a resonator with loss provides an excellent platform to create exceptional points(EPs)in non-Hermitian systems.Most previous studies have focused on the striking intensity feature of EPs,but its phase response is seldom investigated.In this work,we present a thorough study on the phase response of an EP system.Intriguingly,the phase response exhibits distinct behavior depending on the ordering of the ring resonators:when the input light in a bus waveguide is coupled directly or indirectly to the ring with a gain,the phase response is featured by nonmonotonic transition and 2π monotonic transition,respectively.We also prove that the newly identified phase features are theoretically guaranteed.These phase responses produce unique group delays that have never been found in other coupled resonant systems.The results deepen our understanding on EPs in non-Hermitian systems and are potentially useful for practical applications exploiting phase features.

关键词： resonator waveguide coupled

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Top 10 Causes of Death and the Most Growing Causes During the Chinese Spring Festival Holiday-China, 2017-2021

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China CDC weekly 2023年第3期5卷 68-69页

作者： lin, lin Liu, Jiangmei zhou, Maigeng

Figure 1 shows the top 10 causes of death during the Spring Festival holidays from 2017 to 2021 and the 5-year average.The mortality rate during the Spring Festival holidays increased for cerebrovascular disease,ischemic heart disease,and chronic obstructive pulmonary disease(COPD)for both males and females.For males,the rankings of COPD,hypertensive heart disease,and diabetes increased,while the rankings of lung cancer and stomach cancer decreased.For females,the ranking of hypertensive heart disease increased,while the rankings of lung cancer,liver cancer,and stomach cancer decreased.These results suggest that more attention should be paid to patients with chronic diseases during the Spring Festival holiday.

关键词： stomach hypertensive lung

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