RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

Rational screening of metal coating on Zn anode for ultrahigh-cumulative-capacity aqueous zinc metal batteries

Aqueous zinc metal batteries feature intrinsic safety,but suffer from severe dendrite growth and water-derived side reactions.Many metal coatings have been explored for stabilizing Zn metal anode via a trialand-error approach.Here,we propose an exercisable way to screen the potential metal coating on Zn anodes in view of de-polarization effect and dendrite-suppressing ability theoretically.As an output of this screening,cadmium(Cd) metal is checked experimentally.Therefore,symmetric ZnllZn cells using Cd coated Zn(Zn@Cd) exhibit an ultra-long cycle life of 3500 h(nearly 5 months) at a high current density of 10 mA cm^(-2),achieving a record-high cumulative capacity(35 A h cm^(-2)) compared to the previous reports.The full cells of Zn@Cd‖MnO_(2) display a markedly improved cycling performance under harsh conditions including a limited Zn supply(N/P ratio=1.7) and a high areal capacity(3.5 mA h cm^(-2)).The significance of this work lies in not only the first report of Cd coating for stabilizing Zn metal anode,but also a feasible way to screen the promising metal materials for other metal anodes.

New Interpretation of Neonatal Outcomes by Phenotypically Classified Preterm Syndrome:A Retrospective Cohort Study

Objective:The global aim to lower preterm birth rates has been hampered by the insufficient and incomplete understanding of its etiology,classification,and diagnosis.This study was designed to evaluate the association of phenotypically classified preterm syndromes with neonatal outcomes;to what extent would these outcomes be modified after the obstetric interventions,including use of glucocorticoid,magnesium sulfate,and progesterone.Methods:This was a retrospective cohort study conducted at Tongji Hospital(composed of Main Branch,Optical Valley Branch and Sino-French New City Branch)in Wuhan.A total of 900 pregnant women and 1064 neonates were retrospectively enrolled.The outcomes were the distribution of different phenotypes among parturition signs and pathway to delivery,the association of phenotypically classified clusters with short-term unfavorable neonatal outcomes,and to what extent these outcomes could be modified by obstetric interventions.Results:Eight clusters were identified using two-step cluster analysis,including premature rupture of fetal membranes(PPROM)phenotype,abnormal amniotic fluid(AF)phenotype,placenta previa phenotype,mixed condition phenotype,fetal distress phenotype,preeclampsia-eclampsia&hemolysis,elevated liver enzymes,and low platelets syndrome(PE-E&HELLP)phenotype,multiple fetus phenotype,and no main condition phenotype.Except for no main condition phenotype,the other phenotypes were associated with one or more complications,which conforms to the clinical practice.Compared with no main condition phenotype,some phenotypes were significantly associated with short-term adverse neonatal outcomes.Abnormal AF phenotype,mixed condition phenotype,PE-E&HELLP phenotype,and multiple fetus phenotype were risk factors for neonatal small-for gestation age(SGA);placenta previa phenotype was not associated with adverse outcomes except low APGAR score being 0-7 at one min;mixed condition phenotype was associated with low APGAR scores,SGA,mechanical ventilation,and gradeⅢ-Ⅳintraventricular hemorrhage(IVH);fetal distress phenotype was frequently associated with neonatal SGA and mechanical ventilation;PE-E&HELLP phenotype was correlated with low APGAR score being 0-7 at one min,SGA and neonatal intensive care unit(NICU)admission;multiple fetus phenotype was not a risk factor for the outcomes included except for SGA.Not all neonates benefited from obstetric interventions included in this study.Conclusion:Our research disclosed the independent risk of different preterm phenotypes for adverse pregnancy outcomes.This study is devoted to putting forward the paradigm of classifying preterm birth phenotypically,with the ultimate purpose of defining preterm phenotypes based on multi-center studies and diving into the underlying mechanisms.

Nitrogen and fluorine co-doped TiO_(2)/carbon microspheres for advanced anodes in sodium-ion batteries: High volumetric capacity, superior power density and large areal capacity

Fast charging and high volumetric capacity are two of the critical demands for sodium-ion batteries(SIBs).Although nanostructured materials achieve outstanding rate performance,they suffer from low tap density and small volumetric capacity.Therefore,how to realize large volumetric capacity and high tap density simultaneously is very challenging.Here,N/F co-doped TiO_(2)/carbon microspheres(NF- TiO_(2)/C)are synthesized to achieve both of them.Theoretical calculations reveal that N and F co-doping increases the contents of oxygen vacancies and narrows the bandgaps of TiO_(2) and C,improving the electronic conductivity of NF- TiO_(2)/C.Furthermore,NF- TiO_(2)/C exhibits the high binding energy and low diffusion energy barrier of Na+,significantly facilitating Na+storage and Na+diffusion.Therefore,NF- TiO_(2)/C offers a high tap density(1.51 g cm^(-3)),an outstanding rate performance(125.9 mAh g^(-1) at 100 C),a large volumetric capacity(190 mAh cm^(-3) at 100 C),a high areal capacity(4.8 mAh cm^(-2))and an ultra-long cycling performance(80.2%after 10,000 cycles at 10 C)simultaneously.In addition,NF- TiO_(2)/C||Na_(3)V_(2)(PO_(4))_(3) full cells achieve an ultrahigh power density of 25.2 kW kg^(-1).These results indicate the great promise of NF- TiO_(2)/C as a high-volumetric-capacity and high-power-density anode material of SIBs.

The Human-Machine Safety Design of Mechanical Toys for Children

In order to ensure the safety of children while using machineries and avoid harm caused by mechanical toys,this paper analyzes the types and detection standards of children’s toys,discusses the reasons for the harm caused by these toys,and proposes human-machine safety design strategies for children’s toys as reference.

Highly efficient catalyzed by imidazolium-based dual-sulfonic acid functionalized ionic liquids for liquid phase Beckmann rearrangement:experiments and COSMO-RS calculations

A production technique with the high yield and environmentally friendly process need be developed forε-Caprolactam(CPL)in the chemical industry.This technology is highly desired to design and synthesize high--performance catalysts for liquid phase Beckmann rearrangement of cyclohexanone oxime(CHO)to CPL.In this work,3-methyl-1-(propyl-4-sulfonyl)imidazolium methanesulfonate([PHSO_(3)MIM][MSA])with highly efficient and excellent yield is synthesized successfully.When the optimum molar ratio of ZnCl_(2)over[PHSO_(3)MIM][MSA]was 0.02,it exhibits the high selectivity(94%)of CPL at 90℃for 1 h.Interestingly,Fourier-transform infrared(FT-IR)investigations show that the functional Br∅nsted-Lewis acidic types of ionic liquids(ILs)are formed by the uniformly distributed ZnCl_(2)and[PHSO_(3)MIM][MSA].In addition,the hydrogen bond(H-bond)is formed between CHO and ILs.After ten reaction cycles,no significant structure changes are observed in the recovered[PHSO_(3)MIM][MSA]-ZnCl_(2).The solubilities of ILs are predicted by using COSMO-RS model,the results show that[PHSO_(3)MIM][MSA]is a promising candidate for the liquid phase Beckmann rearrangement of CHO into CPL.Finally,a theoretical model of the H-bond interactions between ILs and CHO is further confirmed to support the advance of reaction mechanism.A feasible way is provided for the CPL production technique in the liquid phase Beckmann rearrangement reaction.

Compensation temperature and hysteresis behaviors of a graphene-like bilayer:Monte Carlo Study

Using the Monte Carlo method,the compensation temperature and hysteresis loops of a ferrimagnetic mixed spin-3/2 and spin-5/2 Ising-type graphene-like bilayer are investigated induced by different physical parameters such as crystal field,exchange coupling,external magnetic field,and temperature.The variations of magnetization,magnetic susceptibility,specific heat,and internal energy with the change of temperature are discussed.In addition,we also plot the phase diagrams including transition temperature and compensation temperature.Finally,multiple hysteresis loops under certain parameters are given.

Influences of Ca and Y Addition on the Microstructure and Corrosion Resistance of Vacuum Die-Cast AZ91 Alloy

The influences of Ca and Y additions on the microstructure and corrosion resistance of vacuum die-cast AZ91 alloys were investigated by optical microscope,electron scanning microscope,weight-loss test,and electrochemical corrosion experiment.The results indicate that the Ca or Ca and Y additions refined the microstructure and decreased the amount of Mg17Al12 phase on grain boundaries in the alloys.Meanwhile,the addition of Ca and Y led to the formation of network Al2 Ca phase and rod-like Al2 Y phase,improved the corrosion resistance of AZ91 magnesium alloy.Compared with AZ91 alloy,the corrosion rate of AZ91–1.5Ca–1.0Y alloy was decreased to 16.2%,and its corrosion current density was dropped by one order of magnitude after immersion in 3.5 wt% NaCl solution for 24 h.

Abnormal Brain Structure and Function in First-Episode Childhood- and Adolescence-Onset Schizophrenia: Association with Clinical Symptoms

Dear Editor,Schizophrenia is one of the most complicated and serious psychiatric disorders, and patients often show markedly disrupted structural and functional abnormalities during resting-state imaging scans of the brain. Patients with firstepisode childhood- and adolescence-onset schizophrenia (CAOS) refers to individuals under the age of 18 years whose first episode of illness had occurred before they were 13 years old [1]. The symptoms are similar to adultonset schizophrenia-auditory hallucinations or language deficits and abnormal cognition. However, CAOS patients often present with more severe psychotic symptoms and have a worse prognosis and treatment effect [2].

Antibody-drug conjugates in HER2-positive breast cancer

Antibody-drug conjugates(ADCs)combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads.The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies,direct action and bystander effect of cytotoxic drugs,and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity.ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2(HER2)-positive breast cancer,greatly improving the prognosis of breast cancer patients.Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors.This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.

Highly efficient fiber-shaped organic solar cells toward wearable flexible electronics

Fiber-shaped solar cells(FSCs)show great potential to act as the power source in the wearable electronics field.Due to the unique advantages of the fiber-shaped organic solar cells(FOSCs),such as all-solid-state,ease of fabrication,and environmental friendliness,FOSCs are the strongest candidate among all types of FSCs for wearable electronics.However,the development of FOSCs is seriously lagging behind other types of FSCs.In this work,we demonstrate the efficient FOSCs with non-fullereneacceptors(NFAs)-based light-harvesting materials.The FOSCs present efficiencies exceeding 9%under AM 1.5 G irradiation conditions.The performance influence factors including hole/electron transport layers,active layer,counter electrodes,solvents,and especially,the environmental humidity is systematically studied.The FOSCs not only can easily drive the electrical devices but also can be woven into the textile to charge the smartwatch.The study exhibits the great potential to apply the FOSCs as the power supply source in the wearable electronic field.

SOX2 promotes tumorigenesis and increases the anti-apoptotic property of human prostate cancer cell

SRY-related HMG-box gene 2(SOX2)is one of the key regulatory genes that maintain the pluripotency and self-renewal properties in embryonic stem cells.Here we used immunohistochemistry to analyze the expression of SOX2 in human prostate tissues and found it contributed to tumorigenesis and correlated with histologic grade and Gleason score.We further investigated SOX2’s function in cell growth and apoptosis process by using a human prostate cancer cell line DU145 with SOX2 overexpression or down-regulation.Cell cycle assay revealed that SOX2 promoted cell growth and increased the percentage of cells in S phase.In vitro and in vivo xenograft experiments in NOD/SCID mice further demonstrated that SOX2 increased the apoptosis-resistant properties of DU145 cells with decreased function of store-operated Ca21 entry and reduced expression of Orai1 at both mRNA and protein levels,suggesting a potential mechanism that contributes to the anti-apoptotic property of SOX2.To our knowledge,this study is the first to investigate SOX2’s function in tumorigenesis and apoptosis of human prostate cancer and to elucidate its regulatory effect on the activity of store-operated Ca21 channels.Our results support the concept that SOX2 has the potential to be a significant marker to evaluate the progression of prostate cancer and serve as a potentially useful target for prostate cancer therapy.

Strontium ranelate incorporated 3D porous sulfonated PEEK simulating MC3T3-E1 cell differentiation

Polyetheretherketone(PEEK)has been used as an implant material because it has similar mechani-cal properties to natural bone.However,inferior osseointegration and bioinertness hamper the clinical application of PEEK.In this study,the surfaces of sulfonated three-dimensional(3D)PEEK porous structures were loaded with different concentrations of strontium ranelate,a compound commonly used in the treatment or prevention of osteoporosis by promoting bone formation and inhibiting bone resorption.Field-emission scanning electron microscopy was used to characterize the topography of the structures,elemental carbon,oxygen and strontium contents were mea-sured by X-ray photoelectron spectroscopy,and surface zeta potentials and water-contact angle were also measured.The results indicated that strontium ranelate was successfully loaded onto the 3D porous structures.In vitro cellular results showed that strontium ranelate-treated sulfonated PEEK(SP-SR)strengthened the adhesion of MC3T3-E1 cells.The activity of alkaline phosphatase,collagen secretion and extracellular matrix mineralization deposition of MC3T3-E1 cells were also improved on the surface of SP-SR.These results indicate that SP-SR could serve a new implant candidate for surgical treatment.