Tissue cell differentiation and multicellular evolution via cytoskeletal stiffening in mechanically stressed microenvironments

Evolution of eukaryotes from simple cells to complex multicellular organisms remains a mystery. Our postulate is that cytoskeletal stiffening is a necessary condition for evolution of complex multicellular organisms from early simple eukaryotes. Recent findings show that embryonic stem cells are as soft as primitive eukaryotes-amoebae and that differentiated tissue cells can be two orders of magnitude stiffer than embryonic stem cells. Soft embryonic stem cells become stiff as they differentiate into tissue cells of the complex multicellular organisms to match their microenvironment stiffness. We perhaps see in differentiation of embryonic stem cells (derived from inner cell mass cells) the echo of those early evolutionary events. Early soft unicellular organisms might have evolved to stiffen their cytoskeleton to protect their structural integrity from external mechanical stresses while being able to maintain form, to change shape, and to move.

Recent developments of nanocarbon based supports for PEMFCs electrocatalysts

Nanocarbons,widely and commonly used as supports for supported Pt-based electrocatalysts in PEMFCs,play a significant role in Pt dispersion and accessibility,further determining their corresponding electrocatalytic performance.This paper provides an overview of the nanoarchitectures and surface physicochemical properties of nanocarbons affecting the electrocatalyst performance,with an emphasis on both physical characteristics,including pore structure,and chemical properties,including heteroatom doping and functional carbon-based supports.This review discusses the recent progress in nanocarbon supports,guides the future development direction of PEMFC supports,and provides our own viewpoints for the future research and design of PEMFCs catalysts,advancing the commercialization of PEMFCs.

Transarterial chemoembolization with pirarubicin-eluting microspheres in patients with unresectable hepatocellular carcinoma: Preliminary results

Purpose:To present the early results of pirarubicin-eluting microsphere transarterial chemoembolization(PETACE)for patients with unresectable hepatocellular carcinoma(HCC).Materials and methods:We retrospectively analyzed 55 consecutive patients with HCC who received PE-TACE between April 1,2015 and August 30,2016.The complication rate,tumor response rate,progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Adverse events were generally mild and included abdominal pain and fever,although a major complication was reported in 1 patient(1.8%).During a median follow-up of 10.0 months(range,3.0-24.0 months),14 patients(25.5%)achieved a complete tumor response,25(45.5%)had a partial response,9(16.4%)showed stable disease,and 7(12.7%)had disease progression.The 1-month overall response rate was 70.9%,and the local tumor response rate was 89.0%.The 1-month tumor response rate was 100%for Barcelona Clinic Liver Cancer(BCLC)stage A or B disease and 62.8%for BCLC stage C disease.The median PFS was 6.1 months(95%confidence interval[95%CI],3.4-8.8 months;range,1.0-24.0 months).The median OS was 11.0 months(95%CI,7.1-14.9 months;range,2.0-24.0 months).Kaplan-Meier analysis(log-rank test)found significant differences in OS between patients grouped by tumor number(P=0.006),tumor size(P=0.035),and Eastern Cooperative Oncology Group(ECOG)score(P=0.005).The tumor number(1 vs.>2)was the only factor independently associated with OS(hazard ratio[HR],2.867;95%CI,1.330-6.181;P=0.007).Conclusions:PE-TACE for unresectable HCC may be safe,with favorable tumor response rates and survival time,especially in patients with a single large tumor.Longer follow-up using a larger series is necessary to confirm these preliminary results.

An Fe-N/S-C hybrid electrocatalyst derived from bimetal-organic framework for efficiently electrocatalyzing oxygen reduction reaction in acidic media

Heteroatoms doped Fe-N-C electrocatalysts have been widely acknowledged as one of the most promising candidates to replace Pt-based materials for electrocatalyzing oxygen reduction reaction(ORR).However,the complicated synthesis method and controversial catalytic mechanism represent a substantial impediment as of today.Herein,a very facile strategy to prepare Fe-N/S-C hybrid through pyrolyzing Zn and Fe bimetallic MOFs is rationally designed.The electrocatalytic ORR performance shows a volcanotype curve with the increment of added Fe content.The half-wave potential(E1/2) for ORR at optimized Fe-N/S-C-10%(10%=n(Fe)/(n(Fe)+n(Zn)),n(Fe) and n(Zn) represent the moles of Fe2+ and Zn2+ in the precursors,respectively) shifts significantly to the positive direction of 19.6 mV with respect to that of Pt/C in acidic media,as well as a high 4 e selectivity and methanol tolerance.After 10,000 potential cycles,E1/2 exhibits a small negative shift of-27.5 mV at Fe-N/S-C-10% compared favorably with Pt/C(~141.0 mV).This can be attributed to:(ⅰ) large specific surface area(849 m^(2)/g) and hierarchically porous structure are favorable for the rapid mass transfer and active sites exposure;(ⅱ) the embedded Fecontaining nanoparticles in porous carbon are difficult to be moved and further agglomerated during the electrochemical accelerated aging test,further improving its stability;(ⅲ) there exist small Fecontaining nanoparticles,uniformly doped N and S,abundant Fe-N as efficiently active sites.This work represents a breakthrough in the development of high-efficient non-precious-metal catalysts(NPMCs)to address the current Pt-based electrocatalysts challenges.

Self-renewal memory of tumor-repopulating cells

Tumor-initiating cells(TICs)are a highly tumorigenic subpopulation of solid tumor cells that play a critical role in the initiation of cancer~[1].These tumorigenic cells resist conventional chemotherapeutic drug treatment and are assumed to be playing major roles in cancer relapses after chemotherapy~[2].However,the notion of TICs has been rather controversial.A report shows that a high percentage(】25%)of human melanoma cells can generate a tumor in a NOD-SCID interleukin-2 receptor gamma chain null mouse~[3],suggesting that there is no clonal development of solid tumors,refuting the idea of TICs.We recently developed a method of isolating TICs from cancer cell lines by culturing single individual cells of B16-F1(a melanoma cell line)into 3D soft fibrin gels~[4].In addition to being able to generate local tumors in a

Mechanics and mechanotransduction of tumorigenic cells

Despite significant progress in cancer research during the past decades,yet there are no major breakthroughs that can be translated into major benefits for the general public in terms of treatment or therapy for the complex neoplastic diseases,especially for the malignant solid tumors.This depressing but indisputable fact leads to a call for new ideas to target tumor metastasis by editors of Nature Medicine[1].The real problems are that the fundamental issues of transformation and malignancy in vivo are poorly understood.In a recent review on cancer,

Cellular tension promotes germ layer organization

Understanding the mechanism of gastrulation-the early phase in embryonic development where the blastula loses its symmetry and forms organized germ layers（i.e.endoderm,mesoderm,and ectoderm）-has long been a major challenge to the field of developmental biology.A long standing objective in developmental biology is not only to direct the differentiation of ESCs into specific developmental lineages,but also to organize these differentiated lineages into spatially distinct arrangements resembling the physiological gastrulation.In vivo,research on embryo morphogenesis in lower animals has demonstrated the importance of mechanical forces[1-3].In vitro,experiments of self-sorting utilize pairwise sorting assays where two types of differentiated germ cells are homogeneously mixed[4].It has not been possible to study the or-

Mechanisms of a Synthetic Retinoid in Inhibiting Tumor-Repopulating Cells

Recently we have synthesized a novel small retinoid molecule WYC-209 that can effectively inhibit proliferation of malignant murine melanoma tumor-repopulating cells(TRCs).The molecule can induce 100%TRCs apoptosis at 10μM concentration.However,how WYC-209 induces TRCs apoptosis is still elusive.Here we demonstrate that WYC-209 at>6μM concentration started to induce TRCs apoptosis primarily via the caspase 3 pathway by releasing cytochrome c from mitochondria.Interestingly,we found that at concentrations<6μM WYC-209 induced TRCs to elevate dormancy marker COUP TF1 but induced no changes in apoptosis marker P53.Furthermore,proliferation markers Ki67 and PCNA decreased with the increase of WYC-209 concentrations,suggesting that low concentrations of WYC-209 inhibit TRCs growth by inducing cell dormancy instead of causing apoptosis.In addition,TRC traction forces were almost abolished when WYC-209 concentration was at 5μM,preceding the initiation of apoptosis.Our findings demonstrate that inhibition of TRCs by anti-cancer molecule WYC-209 is concentration-dependent and WYC-209 inhibits cellular force generation of the tumor-repopulating cells before inducing apoptosis.

Nuclear Mechanotransduction in Cellular Mechanobiology and Molecular Mechanomedicine

It is known that mechanical forces play critical roles in physiology and diseases but the underlying mechanisms remain largely unknown[1].Most studies on the role of forces focus on cell surface molecules and cytoplasmic proteins.However,increasing evidence suggests that nuclear mechanotransduction impacts nuclear activities and functions.Recently we have revealed that transgene dihydrofolate reductase(DHFR)gene expression is directly upregulated via cell surface forceinduced stretching of chromatin [2].Here we show that endogenous genes are also upregulated directly by force via integrins.We present evidence on an underlying mechanism of how gene transcription is regulated by force.We have developed a technique of elastic round microgels to quantify 3D tractions in vitro and in vivo[3].We report a synthetic small molecule(which has been stiffened structurally)that inhibits malignant tumor repopulating cell growth in a low-stiffness(force)microenvironment and cancer metastasis in mouse models without detectable toxicity[4].These findings suggest that direct nuclear mechanotransduction impacts mechanobiology and mechanomedicine at cellular and molecular levels.

Mechanoresponsive Gene Upregulation by Force Depends on H3K9Demethylation

All living cells in a human body are made of the same DNA molecule but cells in different tissues express different genes and proteins.How the transcription process is controlled and regulated is largely unknown.Specifically,mechanical forces are increasingly recognized to play critical roles in cell and tissue functions.However,what controls force-induced gene transcription is elusive.Recently we have reported that a local surface force transfers from integrins to the cytoskeleton and the link of nucleoskeleton and the cytoskeleton(LINC)into the nucleus and deforms chromatin directly to induce rapid activation of transgene DHFR.Here we show that endogenous mechanoresponsive genes egr-1 and Cav1 are rapidly upregulated and their upregulation depends on stress angles relative to the cell long axis,suggesting direct impact of these genes by force.Demethylation of histone 3 at lysine 9(H3K9)trimethylation(H3K9me3)at nuclear interiors(euchromatin)is necessary for force-induced transcription upregulation.Our findings suggest that force-rapid upregulation of mechanoresponsive genes by force depends on H3K9me3 demethylation.

N-doped carbon-coated Fe_(3)N composite as heterogeneous electro-Fenton catalyst for efficient degradation of organics

Herein,the application of a N-doped graphitic-carbon-coated iron nitride composite dispersed in a N-doped carbon framework(Fe_(3)N@NG/NC)is investigated as a heterogeneous electro-Fenton(HE-EF)catalyst for the efficient removal of organics.The simultaneous carbonization and ammonia etching of iron-based metal organic framework(Fe-MOF)materials yielded well-dispersed N-doped carbon-coated Fe_(3)N nanoparticles with a diameter of~70 nm.The Fe_(3)N and pyridinic N endowed the composite with high HE-EF activity for decomposing the electrogenerated H_(2)O_(2) to•OH.The Fe_(3)N@NG/NC exhibited outstanding HE-EF performance in removing various organic pollutants with low iron leaching.A removal rate of 97-100%could be obtained for rhodamine B(RhB),dimethyl phthalate,methylene blue,and orange Ⅱ in 120 min at a pH of 5.0.When the solution pH was set to 3.0,5.0,7.0,and 9.0,the removal rate of RhB reached 100%,96%,92%,and 81%,respectively,in 60 min at an optimum voltage of 0.0 V(vs.reversible hydrogen electrode(RHE)).Moreover,the concentration of leached iron was expected to be below 0.03 mg/L in a wide pH range of 3.0-9.0.In addition,the RhB removal efficiency remained as high as 90%after six cycles in the reusability experiments.This work highlights the MOF-derived Fe_(3)N composite as an efficient HE-EF catalyst and the corresponding catalytic mechanism,which facilitates its application in wastewater treatment.

提高池塘养鳝经济效益的技术措施

要提高池塘人工养殖的经济效益,需要从池塘建设、池塘消毒、鳝苗放养、水质水温、饲料投喂、日常管理、疾病防治、成鳝捕捞等采取综合技术措施。

Discrete element modeling and verification of the simulation parameters for chopped hybrid Broussonetia papyrifera stems

In this study,the discrete element software EDEM was applied to establish a simulation model of non-uniform-sized particle units for Broussonetia papyrifera stalks,which aimed to address the low utilization rate of existing Broussonetia papyrifera harvesting machinery,the significant variation between the simulated model of Broussonetia papyrifera stalks and their actual appearance,as well as the absence of contact parameter calibration.Through a combination of the free-fall collision method,inclined plane sliding method,and inclined plane rolling method,numerical simulation was conducted to analyze the pattern of variations in contact parameters between Broussonetia papyrifera stalks and the steel material of the machinery.Accordingly,these parameters were calibrated.The results showed that the coefficient of restitution between Broussonetia papyrifera stalks and steel materials was 0.321,the static friction factor was 0.589,and the rolling friction factor was 0.078.With the parameters of contact between Broussonetia papyrifera stalks as variables and the experimentally measured pile angle as the objective of optimization,the steepest ascent experiment and the three-factor five-level rotation combination experiment were conducted.In this way,a second-order response model was constructed to analyze the relationship between the contact parameters and the pile angle.Through the optimization analysis of experimental data,it was determined that the coefficient of restitution between Broussonetia papyrifera stalks was 0.21,the static friction factor was 0.24,and the rolling friction factor was 0.03.Furthermore,the calibration results were validated through experimentation to show that the relative error between the obtained pile angle under the context of optimal parameter combination and the actual one was 4.11%.In addition,the relative error of mass flow rate in spiral transport was within a reasonable range,this study lays a foundation both theoretically and statistically for the simulation of contact parameters for Broussonetia papyrifera stalk harvesting processing,mechanical harvesting,and so on.

Integrated analysis of lncRNAs expression profiling in systemic lupus erythematosus

To the Editor,Systemic lupus erythematosus(SLE)is a chronic autoimmune disease with serious harm to human health and various clinical manifestations,which is characterized by over-activity of lymphocytes,production of autoantibodies,and effects on multiple organs.1 So far,the pathogenesis of SLE remains unclear;it is believed that genetic,environmental,infectious,and other factors participate in the pathogenesis of SLE.With the gradual in-depth study of transcriptomics,genetic factors may be the root cause of SLE,2 and epigenetics plays an important role in genetic factors of SLE.3 Epigenetics means heritable changes in gene expression without shifting the DNA sequence.The principal mechanisms of epigenetic regulation include histone modification,DNA methylation,and regulation of noncoding RNA.In the past,studies of transcriptomics mainly focused on protein-coding genes.However,protein-coding genes that encode exons account for 1.5%of the genome,and genes without protein-coding capability account for more than 80%of the human genome.4 Therefore,studies of transcriptomics began to pay attention to long noncoding RNAs(lncRNAs),which play key roles in transcription control,posttranscriptional processing,protein metabolism,immune cell differentiation,and immune responses.5 However,knowledge of related lncRNAs in SLE remains limited.

Expression of SALL4 in the synovial tissue of refractory rheumatoid arthritis patients

To the Editor,Rheumatoid arthritis(RA)synovitis is characterized by synovial inflammation,characterized by synovial proliferation,neovascularization,and leukocyte infiltration into the joint space,1 leading to irreversible cartilage and bone damage.2 This synovial inflammation stimulates the formation of pannus,which is an invasive tumor-like mass,ultimately contributing to the pathogenesis of RA.RA shares several similarities with cancer,including joint pain,swelling,and stiffness,which are accompanied by hypoxia in the synovial tissue and tumor environment.3 Spalt-like transcription factor 4(SALL4)plays an essential role in the occurrence and development of tumors.4 However,SALL4 expression in synovial tissue of RA is yet to be investigated.This study aimed to investigate SALL4 expression in synovial tissue derived from patients with RA,using immunohistochemical techniques.

Recent developments in multimodality fluorescence imaging probes

Multimodality optical imaging probes have emerged as powerful tools that improve detection sensitivity and accuracy, important in disease diagnosis and treatment. In this review, we focus on recent developments of optical fluorescence imaging(OFI) probe integration with other imaging modalities such as X-ray computed tomography(CT), magnetic resonance imaging(MRI), positron emission tomography(PET), single-photon emission computed tomography(SPECT), and photoacoustic imaging(PAI). The imaging technologies are briefly described in order to introduce the strengths and limitations of each techniques and the need for further multimodality optical imaging probe development. The emphasis of this account is placed on how design strategies are currently implemented to afford physicochemically and biologically compatible multimodality optical fluorescence imaging probes. We also present studies that overcame intrinsic disadvantages of each imaging technique by multimodality approach with improved detection sensitivity and accuracy.

The effect of five-knee-point acupuncture combined with herbal package warm compress for knee osteoarthritis

Objective:To observe the therapeutic effect differences among five-knee-point acupuncture combined with Chinese medication package warm compress therapy of Shēntòng Zhúyū Decoction(身痛逐瘀汤 generalized pain stasis-expelling decoction),simple five-knee-point acupuncture and simple Chinese medication package warm compress therapy of Shēntòng Zhúyū Decoction in treating knee osteoarthritis(KOA).Methods:A total of 126 KOA patients were randomized into a five-knee-point acupuncture combined with Chinese medication package warm compress therapy group(combined treatment group),where there were 42 cases,including 28 cases of unilateral KOA and 14 cases of bilateral KOA,totally 56 affected knees involved,a Chinese medication package warm compress therapy group(medication package group,42 cases,including 22 cases of unilateral KOA,20 cases of bilateral KOA,totally 62 affected knees involved)and a five-knee-point acupuncture group(five-knee-point group,42 cases,including 27 cases of unilateral KOA,15 cases of bilateral KOA,totally 57 affected knees involved).The basic health education was provided in all of the groups.Additionally,in the combined treatment group,acupuncture was applied to the five knee points on the affected side for 30 min.The warm compress with herbal package of Shēntòng Zhúyū Decoction was given for 10 to 15 min.In the medication package group,the warm compress with Shēntòng Zhúyū Decoction was exerted on the affected area for 10 to 15 min.In the fiveknee-point group,acupuncture was applied to SP 10,ST 34,EX-LE 2,EX-LE 4 and ST 35 and the needles were retained for 30 min.The treatment in each group was given once a day,consecutively for 2 weeks.Before and after treatment,the visual analogue scale(VAS)and Lysholm knee scale were adopted to evaluate the pain degree and knee joint motor function in KOA patients.The clinical therapeutic effects were evaluated too.Results:A total of 121 cases accomplished the final observation and 5 cases were dropped out in the three groups,in which,2 cases(2 affected knees)were dropped out in the combined treatment group,1 case(2 affected knees)in the medication package group and 2 cases(3 affected knees)in the fiveknee-point group.VAS scores after treatment were all lower than those before treatment in the three groups and the scores of Lysholm knee scale were all higher than those before treatment,indicating the significant differences(all P<0.05).The total effective rate was 98.1%(53/54)in the combined treatment group,which was higher than 86.7%(52/60)in the medication package group and 92.6%(50/54)in the five-knee-point group,indicating the significant differences(all P<0.05).After treatment,VAS score(2.24±1.24)in the combined medication group was lower than(2.48±1.08)in the medication package group and(2.63 ± 1.44)in the five-knee-point group,presenting the significant difference(all P<0.05).The score of Lysholm knee scale was(60.50±13.76)in the combined medication group,higher than(52.23±11.65)in the medication package group and(52.14±11.77)in the five-knee-point group,indicting the significant differences(all P<0.05).Conclusion:Compared with the simple application of Chinese medication package warm compress therapy of Shēntòng Zhúyū Decoction or the five-knee-point acupuncture therapy,five-knee-point acupuncture combined with Shēntòng Zhúyū Decoction relieves the clinical symptoms of KOA patients more effectively and achieves a better clinical therapeutic effect.

Recent Advances in the Understanding of the Surface Reconstruction of Oxygen Evolution Electrocatalysts and Materials Development

The electrochemical oxygen evolution reaction(OER)plays an important role in many clean electrochemical energy storage and conversion systems,such as electrochemical water splitting,rechargeable metal–air batteries,and electrochemical CO_(2) reduction.However,the OER involves a complex four-electron process and suffers from intrinsically sluggish kinetics,which greatly impairs the efficiency of electrochemical systems.In addition,state-of-the-art RuO2-based OER electrocatalysts are too expensive and scarce for practical applications.The development of highly active,cost-effective,and durable electrocatalysts that can improve OER performance(activity and durability)is of significant importance in realizing the widespread application of these advanced technologies.To date,considerable progress has been made in the development of alternative,noble metal-free OER electrocatalysts.Among these alternative catalysts,transition metal compounds have received particular attention and have shown activities comparable to or even higher than those of their precious metal counterparts.In contrast to many other electrocatalysts,such as carbon-based materials,transition metal compounds often exhibit a surface reconstruction phenomenon that is accompanied by the transformation of valence states during electrochemical OER processes.This surface reconstruction results in changes to the true active sites and an improvement or reduction in OER catalytic performance.Therefore,understanding the self-reconstruction process and precisely identifying the true active sites on electrocatalyst surfaces will help us to finely tune the properties and activities of OER catalysts.This review provides a comprehensive summary of recent progress made in understanding the surface reconstruction phenomena of various transition metal-based OER electrocatalysts,focusing on uncovering the correlations among structure,surface reconstruction and intrinsic activity.Recent advances in OER electrocatalysts that exhibit a surface self-reconstruction capability are also discussed.We identify possible challenges and perspectives for the development of OER electrocatalysts based on surface reconstruction.We hope this review will provide readers with some guidance on the rational design of catalysts for various electrochemical reactions.

A compact fluorescence/circular dichroism dual-modality probe for detection, differentiation, and detoxification of multiple heavy metal ions via bond-cleavage cascade reactions

Selective detection of multiple analytes in a compact design with dual-modality and theranostic features presents great challenges. Herein, we wish to report a coumarin-thiazolidine masked D-penicillamine based dual-modality fluorescent probe COU-DPA-1 for selective detection, differentiation, and detoxification of multiple heavy metal ions(Ag^(+), Hg^(2+), Cu^(2+)). The probe shows divergent fluorescence(FL)/circular dichroism(CD) responses via divergent bond-cleavage cascade reactions(metal ion promoted C-S cleavage and hydrolysis at two distinctive cleavage sites): FL “turn-off” and CD “turn-on” for Ag+(no hydrolysis), FL “turn-on” and CD “turn-off” for Hg^(+)(imine hydrolysis), and FL “self-threshold ratiometric” and CD “turn-off” for excess Cu^(2+)(lactone and imine hydrolysis), providing the first example of a fluorescence/CD dual-modality probe for multiple species with complimentary responses. Moreover, the bond-cleavage cascade reactions also lead to the formation of D-penicillamine heavy metal ion complexes for potential detoxification treatments.

Strategies for high-performance perovskite solar cells from materials, film engineering to carrier dynamics and photon management

In recent years,halide perovskite solar cells(HPSCs)have attracted a great atten-tion due to their superior photoelectric performance and the low-cost of processing their quality films.In order to commercialize HPSCs,the researchers are focusing on developing high-performance HPSCs.Many strategies have been reported to increase the power conversion efficiency and the long-term stability of HPSCs over the past decade.Herein,we review the latest efforts and the chemical-physical principles for preparing high-efficiency and long-term stability HPSCs in particu-lar,concentrating on the perovskite materials,technologies for perovskite films,charge transport materials and ferroelectric effect to reduce the carrier loss,and photon management via plasmonic and upconversion effects.Finally,the key issues for future researches of HPSCs are also discussed with regard to the require-ments in practical application.