Low-temperature photothermal-induced alkyl radical release facilitates dihydroartemisinin-triggered“valve-off”starvation therapy

The high nutrient and energy demand of tumor cells compared to normal cells to sustain rapid proliferation offer a potentially auspicious avenue for implementing starvation therapy.However,conventional starvation therapy,such as glucose exhaustion and vascular thrombosis,can lead to systemic toxicity and exacerbate tumor hypoxia.Herein,we developed a new“valve-off”starvation tactic,which was accomplished by closing the valve of glucose transporter protein 1(GLUT1).Specifically,dihydroartemisinin(DHA),2,20-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride(AI),and Ink were co-encapsulated in a sodium alginate(ALG)hydrogel.Upon irradiation with the 1064 nm laser,AI rapidly disintegrated into alkyl radicals(R·),which exacerbated the DHA-induced mitochondrial damage through the generation of reactive oxygen species and further reduced the synthesis of adenosine triphosphate(ATP).Simultaneously,the production of R·facilitated DHA-induced starvation therapy by suppressing GLUT1,which in turn reduced glucose uptake.Systematic in vivo and in vitro results suggested that this radical-enhanced“valveoff”strategy for inducing tumor cell starvation was effective in reducing glucose uptake and ATP levels.This integrated strategy induces tumor starvation with efficient tumor suppression,creating a new avenue for controlled,precise,and concerted tumor therapy.

circRNA及其调控动物骨骼肌发育研究进展

环状RNA(circular RNA,circRNA)是一类反向剪接形成的闭合环状RNA分子,广泛存在于生物体内,近年来成为非编码RNA中的研究热点。骨骼肌在生物体中起到协调运动的作用,是维持体内正常代谢和内分泌的器官之一。随着测序技术和生物信息学分析技术的发展,circRNA在动物骨骼肌发育中的功能和调控机制逐渐被揭示。本文就当前circRNA的分子调控机制类型、circRNA经典研究思路及功能研究方法以及circRNA参与骨骼肌正常发育与骨骼肌疾病发生调控的研究进展进行了综述,以期为进一步深入研究circRNA参与骨骼肌生长发育调控的遗传机制以及circRNA相关研究方法提供参考。

Protective effects of sodium butyrate on rotavirus inducing endoplasmic reticulum stress-mediated apoptosis via PERK-eIF2αsignaling pathway in IPEC-J2 cells

Background:Rotavirus(RV)is a major pathogen that causes severe gastroenteritis in infants and young animals.Endoplasmic reticulum(ER)stress and subsequent apoptosis play pivotal role in virus infection.However,the protective mechanisms of intestinal damage caused by RV are poorly defined,especially the molecular pathways related to enterocytes apoptosis.Thus,the aim of this study was to investigate the protective effect and mechanism of sodium butyrate(SB)on RV-induced apoptosis of IPEC-J2 cells.Results:The RV infection led to significant cell apoptosis,increased the expression levels of ER stress(ERS)markers,phosphorylated protein kinase-like ER kinase(PERK),eukaryotic initiation factor 2 alpha(eIF2α),caspase9,and caspase3.Blocking PERK pathway using specific inhibitor GSK subsequently reversed RV-induced cell apoptosis.The SB treatment significantly inhibited RV-induced ERS by decreasing the expression of glucose regulated protein 78(GRP78),PERK,and eIF2α.In addition,SB treatment restrained the ERS-mediated apoptotic pathway,as indicated by downregulation of C/EBP homologous protein(CHOP)mRNA level,as well as decreased cleaved caspase9 and caspase3 protein levels.Furthermore,siRNA-induced GPR109a knockdown significantly suppressed the protective effect of SB on RV-induced cell apoptosis.Conclusions:These results indicate that SB exerts protective effects against RV-induced cell apoptosis through inhibiting ERS mediated apoptosis by regulating PERK-eIF2αsignaling pathway via GPR109a,which provide new ideas for the prevention and control of RV.

Identification of microsatellites in cattle unigenes

To identify EST-SSR molecular markers, 41,986 cattle UniGene sequences from NCBI were mined for analyzing SSRs. A total of 1,831 SSRs were identified from 1,666 ESTs, which represented an average density of 19.88 kb per SSR. The frequency of EST-SSRs was 4.0%. The dinucleotide repeat motif was the most abundant SSR, accounting for 54%, followed by 22%, 13%, 7% and 4%, respectively, for tri-, hexa-, penta- and tetra-nucleotide repeats. Depending upon the length of the repeat unit, the length of microsatellites varied from 14 to 86 bp. Among the di- and tri-nucleotide repeats, AC/TG （57%） and AGC （12%） were the most abundant type. Annotation of EST-SSRs was also carried out. Three hundred primer pairs were randomly designed using Prime Premier 5.0 program and Oligo 5.0 for further experimental validation.

A rare case of mitral valve dissection and aortic-left ventricular tunnel associated with possible autoimmune vasculitis

We report a very rare case of mitral valve dissection and aorticleft ventricular tunnel caused by possible autoimmune vasculitis.We suspected Behcet’s disease in this patient.There was no obvious clinical evidence of infective endocarditis.Echocardiography is the diagnostic tool of choice to recognize valvular dysfunction,related pathology and possible complications.The patient may require immunosuppressive therapy due to the high likelihood of recurrence perioperation period.

Hyperoside promotes pollen tube growth by regulating the depolymerization effect of actin depolymerizing factor 1 on microfilaments in okra

Mature pollen germinates rapidly on the stigma,extending its pollen tube to deliver sperm cells to the ovule for fertilization.The success of this process is an important factor that limits output.The flavonoid content increased signi ficantly during pollen germination and pollen tube growth,which suggests it may play an important role in these processes.However,the speci fi c mechanism of this involvement has been little researched.Our previous research found that hyperoside can prolong the flowering period of Abelmoschus esculentus(okra),but its speci fic mechanism is still unclear.Therefore,in this study,we focused on the effect of hyperoside in regulating the actin-depolymerizing factor(ADF),which further affects the germination and growth of pollen.We found that hyperoside can prolong the effective pollination period of okra by 2-3-fold and promote the growth of pollen tubes in the style.Then,we used Nicotiana benthamiana cells as a research system and found that hyperoside accelerates the depolymerization of intercellular micro fi laments.Hyperoside can promote pollen germination and pollen tube elongation in vitro.Moreover,AeADFl was identi fied out of all AeADF genes as being highly expressed in pollen tubes in response to hyperoside.In addition,hyperoside promoted AeADF1-mediated micro filament dissipation according to micro filament severing experiments in vitro.In the pollen tube,the gene expression of AeADFl was reduced to 1/5 by oligonucleotide transfection.The decrease in the expression level of AeADFl partially reduced the promoting effect of hyperoside on pollen germination and pollen tube growth.This research provides new research directions for flavonoids in reproductive development.

A Monophyletic Status of Axis Genus in Subfamily Cervinae Supported by the Complete Mitochondrial Genome of Chinese Hog Deer(Axis porcinus)

Hog deer(Axis porcinus)is a small mammal and listed in the International Union for Conservation of Nature.However,phylogenetic position of hog deer within Axis genus has remained controversial.In the present study,we first assembled complete mitochondrial genome of Chinese hog deer reared in Chengdu Zoo,Sichuan,by the second-generation sequencing technology.This newly assembled mitochondrial genome of hog deer is 16376 bp in length and consists of 13 protein-encoding genes,23 transfer RNA genes and 2 ribosomal RNA genes.Phylogenetic analyses based on complete mitochondrial genome and cytochrome b gene sequences revealed that hog deer is closely clustered together and placed with sister taxon of spotted deer(A.Axis),which therefore supported monophyletic statue of Axis genus.Furthermore,considerable genetic differentiation,up to 139 mutations of complete mitochondrial genome was revealed between geographical populations of hog deer in France and Southeast Asia.However,only six variable sites(nucleotide diversity of 0.00007)and four haplotypes(haplotype diversity of 0.533)were totally detected among ten newly sequenced Chinese hog deer.The results provide a better understanding on the phylogeny of hog deer.

Ultrasound deep brain stimulation decelerates telomere shortening in Alzheimer’s disease and aging mice

Telomere length is a reliable biomarker for health and longevity prediction in both humans and animals.The common neuromodulation techniques,including deep brain stimulation(DBS)and optogenetics,have excellent spatial resolution and depth penetration but require implementation of electrodes or optical fibers.Therefore,it is important to develop methods for noninvasive modulation of telomere length.Herein,we reported on a new method for decelerating telomere shortening using noninvasive ultrasound deep brain stimulation(UDBS).Firstly,we found that UDBS could activate the telomerase-associated proteins in normal mice.Then,in the Alzheimer’s disease mice,UDBS was observed to decelerate telomere shortening of the cortex and myocardial tissue and to effectively improve spatial learning and memory abilities.Similarly,UDBS was found to significantly slow down telomere shortening of the cortex and peripheral blood,and improve motor and cognitive functions in aging mice.Finally,transcriptome analysis revealed that UDBS upregulated the neuroactive ligand-receptor interaction pathway.Overall,the present findings established the critical role of UDBS in delaying telomere shortening and indicated that ultrasound modulation of telomere length may constitute an effective therapeutic strategy for aging and aging-related diseases.

Oleic Acid and Eicosapentaenoic Acid Reverse Palmitic Acid-induced Insulin Resistance in Human HepG2 Cells via the Reactive Oxygen Species/JUN Pathway

Oleic acid(OA),a monounsaturated fatty acid(MUFA),has previously been shown to reverse saturated fatty acid palmitic acid(PA)-induced hepatic insulin resistance(IR).However,its underlying molecular mechanism is unclear.In addition,previous studies have shown that eicosapentaenoic acid(EPA),aω-3 polyunsaturated fatty acid(PUFA),reverses PA-induced muscle IR,but whether EPA plays the same role in hepatic IR and its possible mechanism involved need to be further clarified.Here,we confirmed that EPA reversed PA-induced IR in HepG2 cells and compared the proteomic changes in HepG2 cells after treatment with different free fatty acids(FFAs).A total of 234 proteins were determined to be differentially expressed after PA+OA treatment.Their functions were mainly related to responses to stress and endogenous stimuli,lipid metabolic process,and protein binding.For PA+EPA treatment,the PA-induced expression changes of 1326 proteins could be reversed by EPA,415 of which were mitochondrial proteins,with most of the functional proteins involved in oxidative phosphorylation(OXPHOS)and tricarboxylic acid(TCA)cycle.Mechanistic studies revealed that the protein encoded by JUN and reactive oxygen species(ROS)play a role in OA-and EPA-reversed PA-induced IR,respectively.EPA and OA alleviated PA-induced abnormal adenosine triphosphate(ATP)production,ROS generation,and calcium(Ca^(2+))content.Importantly,H_(2)O_(2)-activated production of ROS increased the protein expression of JUN,further resulting in IR in HepG2 cells.Taken together,we demonstrate that ROS/JUN is a common response pathway employed by HepG2 cells toward FFA-regulated IR.

Noninvasive Ultrasound Deep Brain Stimulation for the Treatment of Parkinson’s Disease Model Mouse

Modulating basal ganglia circuitry is of great signifcance in the improvement of motor function in Parkinson’s disease(PD).Here,for the frst time,we demonstrate that noninvasive ultrasound deep brain stimulation(UDBS)of the subthalamic nucleus(STN)or the globus pallidus(GP)improves motor behavior in a subacute mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Immunohistochemical c-Fos protein expression confrms that there is a relatively high level of c-Fos expression in the STN-UDBS and GP-UDBS group compared with sham group(both p<0.05).Furthermore,STN-UDBS or GPUDBS signifcantly increases the latency to fall in the rotarod test on day 9(p<0.05)and decreases the time spent climbing down a vertical rod in the pole test on day 12(p<0.05).Moreover,our results reveal that STN-UDBS or GP-UDBS protects the dopamine(DA)neurons from MPTP neurotoxicity by downregulating Bax(p<0.001),upregulating Bcl-2(p<0.01),blocking cytochrome c(Cyt C)release from mitochondria(p<0.05),and reducing cleaved-caspase 3 activity(p<0.01)in the ipsilateral substantia nigra(SN).Additionally,the safety of ultrasound stimulation is characterized by hematoxylin and eosin(HE)and Nissl staining;no hemorrhage or tissue damage is detected.Tese data demonstrate that UDBS enables modulation of STN or GP neural activity and leads to neuroprotection in PD mice,potentially serving as a noninvasive strategy for the clinical treatment of PD.

Noninvasive ultrasound deep brain stimulation of nucleus accumbens induces behavioral avoidance

Ultrasound stimulation is an emerging noninvasive option in treating neuropsychiatric disorders. The present study investigates the behavioral alterations resulting from ultrasound stimulation on the nucleus accumbens(NAc) in freely moving mice. Our results show that an acute ultrasound stimulation on the NAc, rather than the visual cortex or auditory cortex, led to a pronounced avoidance behavior, while repeated NAc ultrasound stimulation resulted in an obvious conditioned place aversion with changes in synaptic protein(Glu A1/2 subunit) expression. Notably, NAc ultrasound stimulation suppressed the morphine-induced conditioned place preference. The results provide evidence that NAc ultrasound stimulation can be applied as a potential noninvasive therapeutic option in treating psychiatric disorders.

Emission-tunable Ba_(2)Y_(1-x)Sc_(x)NbO_(6):Bi^(3+)(0≤x≤1.0)phosphors for white LEDs

Here,we report a series of Bi^(3+)-doped Ba_(2)Y_(1-x)Sc_(x)NbO_(6)(0≤x≤1.0 mol)phosphors by using the traditional high temperature solid-state reaction.To achieve the structural and photoluminescent(PL)information,several experimental characterizations and theoretical calculations were carried out,including X-ray diffraction(XRD),Rietveld refinement,UV-visible diffuse reflectance and PL spectra,temperature dependent PL spectra,and density functional theo retical(DFT)calculations.The XRD results show that the Bi^(3+)-doped Ba_(2)Y_(1-x)Sc_(x)NbO_(6)samples belong to the double-perovskite phase with a cubic space group of Fm3 m,and the diffraction positions shift toward high diffraction angle when the larger Y^(3+)ions are gradually replaced by the smaller Sc^(3+)ions.In addition,the refined XRD findings show that the Bi^(3+)ions tend to substitute the Y^(3+)and Sc^(3+)sites in the Bi^(3+)-doped Ba_(2)Y_(1-x)Sc_(x)NbO_(6)0<x<1.0 mol)solid solutions.The PL spectra show that the emission positions of the solid solution samples tune from446 to 497 nm with the increase of Sc^(3+) content,which can be attributed to the modification of crystal field strength around Bi^(3+)ions.Moreover,there is energy transfer from the Ba_(2)YNbO_(6)host to Bi^(3+)ions,which is dominated by a resonant type via a dipole-quadrupole(d-q)interaction.The Ba_(2)Y_(0.6)Sc_(0.4)NbO_(6):0.02 molBi^(3+)shows the strongest PL intensity under 365 nm excitation,with the best quantum efficiency(QE)of 68%,and it keeps 60%of the room temperature emission intensity when the temperature increases to 150℃,meaning that the Ba_(2)Y_(0.6)Sc_(0.4)NbO_(6):Bi^(3+)features excellent thermal quenching of luminescence.By combining this optimal sample with a commercial red-emitting Sr_(2)Si_(5)N_(8):Eu^(2+)phosphor,and a commercial 365 nm UV LED chip,a white LED device,with the color temperature(CT)of 3678 K,color rendering index(CRI)of 67.9,and CIE coordinates at(0.371,0.376),is achieved.

Noninvasive Ultrasound Stimulation of Ventral Tegmental Area Induces Reanimation from General Anaesthesia in Mice

Evidence in animals suggests that deep brain stimulation or optogenetics can be used for recovery from disorders of consciousness(DOC).However,these treatments require invasive procedures.This report presents a noninvasive strategy to stimulate central nervous system neurons selectively for recovery from DOC in mice.Through the delivery of ultrasound energy to the ventral tegmental area,mice were aroused from an unconscious,anaesthetized state in this study,and this process was controlled by adjusting the ultrasound parameters.The mice in the sham group under isoflurane-induced,continuous,steady-state general anaesthesia did not regain their righting reflex.On insonation,the emergence time from inhaled isoflurane anaesthesia decreased(sham.13.63±0.53 min,ultrasound.1.5±0.19 min,p<0.001).Further,the induction time(sham.12.0±0.6 min,ultrasound.17.88±0.64 min,p<0.001)and the concentration for 50%of the maximal effect(EC50)of isoflurane(sham.0.6%,ultrasound.0.7%)increased.In addition,ultrasound stimulation reduced the recovery time in mice with traumatic brain injury(sham.30.38±1.9 min,ultrasound.7.38±1.02 min,p<0.01).This noninvasive strategy could be used on demand to promote emergence from DOC and may be a potential treatment for such disorders.

Self-Navigated 3D Acoustic Tweezers in Complex Media Based on Time Reversal

Acoustic tweezers have great application prospects because they allow noncontact and noninvasive manipulation of microparticles in a wide range of media.However,the nontransparency and heterogeneity of media in practical applications complicate particle trapping and manipulation.In this study,we designed a 1.04 MHz 256-element 2D matrix array for 3D acoustic tweezers to guide and monitor the entire process using real-time 3D ultrasonic images,thereby enabling acoustic manipulation in nontransparent media.Furthermore,we successfully performed dynamic 3D manipulations on multiple microparticles using multifoci and vortex traps.We achieved 3D particle manipulation in heterogeneous media(through resin baffle and ex vivo macaque and human skulls)by introducing a method based on the time reversal principle to correct the phase and amplitude distortions of the acoustic waves.Our results suggest cutting-edge applications of acoustic tweezers such as acoustical drug delivery,controlled micromachine transfer,and precise treatment.

Sustained and efficient remediation of biochar immobilized with Sphingobium abikonense on phenanthrene-copper co-contaminated soil and microbial preferences of the bacteria colonized in biochar

Immobilized microbial technology has been widely used in wastewater treatment,but it has been used less frequently for soil remediation,particularly in sites that are co-contaminated with organic compounds and heavy metals.In addition,there is limited knowledge on the efficiency of remediation and microbial preferences to colonize the immobilized carriers.In this study,biochar immobilized with Sphingobium abikonense was introduced to remediate soils that were co-contaminated with phenanthrene(PHE)and copper(Cu),and the mechanisms of microbial assemblage were investigated.The immobilized microbial biochar maintained a degradation rate of more than 96%in both the first(0-6 d)and second(6-12 d)contamination periods.The addition of biochar increased the proportion of Cu bound to organic matter,and Fe-Mn oxide bound Cu in the soil.In addition,both Cu and PHE could be adsorbed into biochar pellets in the presence or absence of immobilized S.abikonense.The presence of biochar significantly increased the abundance of bacteria,such as Luteibacter,Bordetella and Dyella,that could degrade organic matter and tolerate heavy metals.Notably,the biochar could specifically select host microbes from the soil for colonization,while the presence of S.abikonense affected this preference.The autonomous selection facilitates the degradation of PHE and/or the immobilization of Cu in the soil.These results provide a green approach to efficiently and sustainably remediate soil co-contaminated with PHE and Cu and highlight the importance of microbial preference colonized in immobilized carriers.

The Emergence of Functional Ultrasound for Noninvasive Brain-Computer Interface

A noninvasive brain-computer interface is a central task in the comprehensive analysis and understanding of the brain and is an important challenge in international brain-science research.Current implanted brain-computer interfaces are cranial and invasive,which considerably limits their applications.The development of new noninvasive reading and writing technologies will advance substantial innovations and breakthroughs in the field of brain-computer interfaces.Here,we review the theory and development of the ultrasound brain functional imaging and its applications.Furthermore,we introduce latest advancements in ultrasound brain modulation and its applications in rodents,primates,and human;its mechanism and closed-loop ultrasound neuromodulation based on electroencephalograph are also presented.Finally,high-frequency acoustic noninvasive brain-computer interface is prospected based on ultrasound super-resolution imaging and acoustic tweezers.