Fixed-Time Gradient Flows for Solving Constrained Optimization: A Unified Approach

The accelerated method in solving optimization problems has always been an absorbing topic.Based on the fixedtime(FxT)stability of nonlinear dynamical systems,we provide a unified approach for designing FxT gradient flows(FxTGFs).First,a general class of nonlinear functions in designing FxTGFs is provided.A unified method for designing first-order FxTGFs is shown under Polyak-Łjasiewicz inequality assumption,a weaker condition than strong convexity.When there exist both bounded and vanishing disturbances in the gradient flow,a specific class of nonsmooth robust FxTGFs with disturbance rejection is presented.Under the strict convexity assumption,Newton-based FxTGFs is given and further extended to solve time-varying optimization.Besides,the proposed FxTGFs are further used for solving equation-constrained optimization.Moreover,an FxT proximal gradient flow with a wide range of parameters is provided for solving nonsmooth composite optimization.To show the effectiveness of various FxTGFs,the static regret analyses for several typical FxTGFs are also provided in detail.Finally,the proposed FxTGFs are applied to solve two network problems,i.e.,the network consensus problem and solving a system linear equations,respectively,from the perspective of optimization.Particularly,by choosing component-wisely sign-preserving functions,these problems can be solved in a distributed way,which extends the existing results.The accelerated convergence and robustness of the proposed FxTGFs are validated in several numerical examples stemming from practical applications.

A Data-Driven Rutting Depth Short-Time Prediction Model With Metaheuristic Optimization for Asphalt Pavements Based on RIOHTrack

Rutting of asphalt pavements is a crucial design criterion in various pavement design guides. A good road transportation base can provide security for the transportation of oil and gas in road transportation. This study attempts to develop a robust artificial intelligence model to estimate different asphalt pavements’ rutting depth clips, temperature, and load axes as primary characteristics. The experiment data were obtained from19 asphalt pavements with different crude oil sources on a 2.038km long full-scale field accelerated pavement test track(Road Track Institute, RIOHTrack) in Tongzhou, Beijing. In addition,this paper also proposes to build complex networks with different pavement rutting depths through complex network methods and the Louvain algorithm for community detection. The most critical structural elements can be selected from different asphalt pavement rutting data, and similar structural elements can be found. An extreme learning machine algorithm with residual correction(RELM) is designed and optimized using an independent adaptive particle swarm algorithm. The experimental results of the proposed method are compared with several classical machine learning algorithms, with predictions of average root mean squared error(MSE), average mean absolute error(MAE), and a verage mean absolute percentage error(MAPE) for 19 asphalt pavements reaching 1.742, 1.363, and 1.94% respectively. The experiments demonstrate that the RELM algorithm has an advantage over classical machine learning methods in dealing with non-linear problems in road engineering. Notably, the method ensures the adaptation of the simulated environment to different levels of abstraction through the cognitive analysis of the production environment parameters. It is a promising alternative method that facilitates the rapid assessment of pavement conditions and could be applied in the future to production processes in the oil and gas industry.

Exponential Convergence of Primal-Dual Dynamical System for Linear Constrained Optimization

Dear editor,Primal-dual dynamics(PDD)and its variants are prominent first-order continuous-time algorithms to determine the primal and dual solutions of a constrained optimization problem(COP).Due to the simple structure,they have received widespread attention in various fields,such as distributed optimization[1],power systems[2],and wireless communication[3].In view of their wide applications,there are numerous theoretic studies on the convergence properties of PDD and its variants,including the exponential stability analysis[4]-[9].

Tissue Engineering and Regulatory Science

Tissue engineering has successfully evolved from its original concept[1]into medical products with a rapid pace of develop-ment and a multi-billion dollar market[2].Compared with tradi-tional medical products,tissue-engineered medical products(TEMPs)have distinct characteristics that provide unique benefits for the repair and regeneration of damaged or diseased tissues or organs[1,2].

基于纳米材料的可控组装策略和刺激响应型传感机制用于恶性肿瘤的靶向精准治疗研究

近几十年来,纳米材料在各个领域得到了广泛的应用,基于纳米材料的诊疗探针为癌症精准治疗带来了巨大的前景和机遇.近年来,本课题组通过研究纳米材料的可控生长和组装策略,构建了多种灵活的药物载体,并发展新型的刺激响应型生物传感体系,用于肿瘤的化疗、光动力治疗、光热治疗和基因治疗.在化疗方面,通过在上转换纳米颗粒、碳纳米管和Janus纳米粒子表面修饰DNA或RNA纳米结构构建复合药物载体,或利用核酸自组装形成的三维(3D)纳米结构构建药物递送系统,实现肿瘤的靶向治疗和药物的可控释放.在光动力治疗方面,建立了基于上转换纳米颗粒的新型光动力纳米治疗剂,它具有更高的能量传递效率和更多的活性氧的产量.在光热治疗方面,构建了多种新型复合纳米材料来提高光热转换能力.最后,还考察了纳米材料在肿瘤基因治疗方面的应用潜力.综上,本课题组基于纳米材料的可控生长和组装策略构建了多种诊疗探针,构建了刺激响应型生物传感体系,并验证了诊疗探针在恶性肿瘤靶向精准治疗中的应用潜力.

Status and developmental trends in recombinant collagen preparation technology

Recombinant collagen is a pivotal topic in foundational biological research and epitomizes the application of critical bioengineer-ing technologies.These technological advancements have pro-found implications across diverse areas such as regenerative medicine,organ replacement,tissue engineering,cosmetics and more.Thus,recombinant collagen and its preparation methodologies rooted in genetically engineered celis mark pivotal milestones in medical product research.This article pro-vides a comprehensive overview of the current genetic engi-neering technologies and methods used in the production of recombinant collagen,as well as the conventional production process and gquality control detection methods for this material.Furthermore,the discussion extends to foresee the strides in physical transfection and magnetic control sorting studies,envisioning an enhanced preparation of recombinant collagen-seeded cells to further fuel recombinant collagen production.

Highly selective adsorption of light hydrocarbons in a HKUST-like MOF constructed from spirobifluorene-based octacarboxylate ligand by a substitution strategy

Metal-organic frameworks(MOFs)with HKUST-like tbo structures have been paid specific attention for gas sorption and separation because of their specific pore features.According to the geometric similarity of spirobifluorene and[Cu_(2)(O_(2)CR)_(4)]paddlewheel secondary building units(Cu_(2)SBUs)in HKUST-1,we attempted to rationally construct a HKUST-like MOF by a substitution strategy.Using a judiciously designed octatopic carboxylate ligand,a copper-organic framework,JUC-220,was synthesized.The crystals of JUC-220 exhibited characteristic features in cubic with disorder,possibly due to the disorder substitution and high symmetry of tbo topology.Two related HKUST-like structure models were considered.Thanks to the suitable pore size and specific pore shapes,the adsorption selectivities of JUC-220 for C_(3)H_(8)/CH_(4)(5/85)and C_(2)H_(6)/CH_(4)(10/85)gas mixtures were as high as 736 and 46 respectively at 298 K and 1 bar.Specially,JUC-220 exhibited excellent trace adsorption performance of C_(3)H_(8)and C_(2)H_(6)as well as reverse adsorption behavior of C_(2)H_(6)/C_(2)H_(4).Thus,JUC-220 serves as an example of HKUST-like MOF with disorder for light hydrocarbons separation and the implementation of substitution which can be used to explore more porous MOFs.

Progress and prospect of technical and regulatory challenges on tissue-engineered cartilage as therapeutic combination product

Hyaline cartilage plays a critical role in maintaining joint function and pain.However,the lack of blood supply,nerves,and lymphatic vessels greatly limited the self-repair and regeneration of damaged cartilage,giving rise to various tricky issues in medicine.In the past 30 years,numerous treatment techniques and commercial products have been developed and practiced in the clinic for promoting defected cartilage repair and regeneration.Here,the current therapies and their relevant advantages and disadvantages will be summarized,particularly the tissue engineering strategies.Furthermore,the fabrication of tissue-engineered cartilage under research or in the clinic was discussed based on the traid of tissue engineering,that is the materials,seed cells,and bioactive factors.Finally,the commercialized cartilage repair products were listed and the regulatory issues and challenges of tissue-engineered cartilage repair products and clinical application would be reviewed.

Plain metallic biomaterials:opportunities and challenges

The‘plainification of materials’has been conceptualized to promote the sustainable development of materials.This perspective,for the first time in the field of biomaterials,proposes and defines‘plain metallic biomaterials(PMBs)’with demonstrated research and application case studies of pure titanium with high strength and toughness,and biodegradable,fine-grained and high-purity magnesium.Then,after discussing the features,benefits and opportunities of PMBs,the challenges are analyzed from both technical and regulatory aspects.Regulatory perspectives on PMB-based medical devices are also provided for the benefit of future research,development and commercialization.

Dihydroartemisinin increased the abundance of Akkermansia muciniphila by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD-1 immunotherapy

The effect of anti-programmed cell death 1(anti-PD-1)immunotherapy is limited in patients with hepatocellular carcinoma(HCC).Yes-associated protein 1(YAP1)expression increased in liver tumor cells in early HCC,and Akkermansia muciniphila abundance decreased in the colon.The response to anti-PD-1 treatment is associated with A.muciniphila abundance in many tumors.However,the interaction between A.muciniphila abundance and YAP1 expression remains unclear in HCC.Here,anti-PD-1 treatment decreased A.muciniphila abundance in the colon,but increased YAP1 expression in the tumor cells by mice with liver tumors in situ.Mechanistically,hepatocyte-specific Yap1 knockout(Yap1^(LKO))maintained bile acid homeostasis in the liver,resulting in an increased abundance of A.muciniphila in the colon.Yap1 knockout enhanced anti-PD-1 efficacy.Therefore,YAP1 inhibition is a potential target for increasing A.muciniphila abundance to promote anti-PD-1 efficacy in liver tumors.Dihydroartemisinin(DHA),acting as YAP1 inhibitor,increased A.muciniphila abundance to sensitize anti-PD-1 therapy.A.muciniphila by gavage increased the number and activation of CD8^(+)T cells in liver tumor niches during DHA treatment or combination with anti-PD-1.Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.

Biodegradable metals for bone defect repair:A systematic review and meta-analysis based on animal studies

Biodegradable metals are promising candidates for bone defect repair.With an evidence-based approach,this study investigated and analyzed the performance and degradation properties of biodegradable metals in animal models for bone defect repair to explore their potential clinical translation.Animal studies on bone defect repair with biodegradable metals in comparison with other traditional biomaterials were reviewed.Data was carefully collected after identification of population,intervention,comparison,outcome,and study design(PICOS),and following the inclusion criteria of biodegradable metals in animal studies.30 publications on pure Mg,Mg alloys,pure Zn and Zn alloys were finally included after extraction from a collected database of 2543 publications.A qualitative systematic review and a quantitative meta-analysis were performed.Given the heterogeneity in animal model,anatomical site and critical size defect(CSD),biodegradable metals exhibited mixed effects on bone defect repair and degradation in animal studies in comparison with traditional non-degradable metals,biodegradable polymers,bioceramics,and autogenous bone grafts.The results indicated that there were limitations in the experimental design of the included studies,and quality of the evidence presented by the studies was very low.To enhance clinical translation of biodegradable metals,evidence-based research with data validity is needed.Future studies should adopt standardized experimental protocols in investigating the effects of biodegradable metals on bone defect repair with animal models.

A MyD88-JAK1-STAT1 complex directly induces SOCS-1 expression in macrophages infected with Group A Streptococcus

Some pathogens can use host suppressor of cytokine signaling I （SOCS-1）, an important negative-feedback molecule, as the main mode of immune evasion. Here we found that group A Streptococcus （GAS） is capable of inducing SOCS-1 expression in RAW264.7 and BMDM macrophages. IFN-p plays a role in GAS-induced SOCS-1 expression in macrophages following the induction of cytokine expression by GAS, representing the classical pathway of SOCS-1 expression. However, GAS also induced STAT1 activation and SOCS-1 expression when GAS-infected cells were incubated with anti-IFN-p monoclonal antibody in this study. Moreover, upon comparing TLR4-/- BMDM macrophages with wild-type （WT） cells, we found that TLR4 also plays an essential role in the induction of SOCS-1. MyD88, which is an adaptor protein for TLR4, contributes to STAT1 activation and phosphorylation by forming a complex with Janus kinase 1 （JAK1） and signal transducer and activator of transcription 1 （STAT1） in macrophages. GAS-stimulated expression of STAT1 was severely impaired in MyD88-/- macrophages, whereas expression of JAK1 was unaffected, suggesting that MyD88 was involved in STAT1 expression and phosphorylation. Together, these data demonstrated that in addition to IFN-p signaling and MyD88 complex formation, JAK1 and STAT1 act in a novel pathway to directly induce SOCS-1 expression in GAS-infected macrophages, which may be more conducive to rapid bacterial infection.

A regulatory perspective on recombinant collagen-based medical devices

As a class of novel biomaterials manufactured by synthetic biology technologies,recombinant collagens are candidates for a variety of medical applications.In this article,a regulatory scientific perspective on recombinant collagens and their medical devices is presented with a focus on the definition,translation,classification and technical review.Recombinant collagens are categorized as recombinant human collagen,recombinant humanized collagen and recombinant collagen-like protein,as differentiated by specific compositions and structures.Based on their intended uses and associated risks,recombinant collagen-based medical devices are generally classified as Class Ⅱ or Ⅲ in China.The regulatory review of recombinant collagen-based medical devices aims to assess their safety and efficacy demonstrated by scientific evidences generated from preclinical and clinical evaluations.Taken together,opportunities as well as challenges for their future clinical translation of recombinant collagen-based medical devices abound,which highlights the essential role of regulatory science to provide new tools,standards,guidelines and methods to evaluate the safety and efficacy of medical products.

Quality of reporting and adherence to the ARRIVE guidelines 2.0 for preclinical degradable metal research in animal models of bone defect and fracture:a systematic review

In vivo testing is crucial for the evaluation of orthopedic implant efficacy and safety.However,the translation and reproducibility of preclinical animal experiments are not always satisfactory,and reporting quality is among the essential factors that ensure appropriate delivery of information.In this study,we assessed the reporting quality of in vivo investigations that examined the use of degradable metal materials in fracture or bone defect repair.We employed scientific databases,such as PubMed,EMBASE,Web of Science,Cochrane Library,CNKI,WanFang,VIP and Sinomed to screen for in vivo investigations on fracture or bone defect repair using degradable metal materials,and extracted both epidemiological and main characteristics of eligible studies,and assessed their reporting quality using the ARRIVE guidelines 2.0.Overall,263 publications were selected,including 275 animal experiments.The overall coincidence rate of Essential 10(22 sub-items)and Recommended Set(16 sub-items)were 42.0%and 41.5%,respectively.Based on our analysis,the reporting quality of the published in vivo investigations examining fracture/bone defect repair with degradable metal materials was low,and there was a lack of transparent,accurate and comprehensive reporting on key elements of the experimental design and other elements that are meant to avoid bias.

Biomaterials and regulatory science

The fast development of both biomaterials and regulatory science calls for a convergence,which is addressed in this article via their link through medical products of biomaterials and related safety and efficacy evaluation.The updated definition of biomaterials,and concepts of biomaterials-related medical products and so-called medical-grade and implantable materials are firstly introduced.Then a brief overview of the concept and history of regulatory science and its assessment of safety and efficacy of medical products,as well as the currently ongoing biomaterials-related regulatory science programs are presented.Finally,the opportunities provided by regulatory science for biomaterials as well as challenges on how to develop a biomaterials-based regulatory science system are discussed.As the first article in the field to elucidate the relationship between biomaterials and regulatory science,key take-home messages include(1)biomaterials alone are not medical products;(2)regulatory authorities approve/clear final medical products,not biomaterials;(3)there is no definition/regulation on the so-called medical-grade or implantable materials;and(4)safety and efficacy refer to final medical products,not biomaterials alone.