查看更多>>摘要：Mitochondrial dysfunction is a hallmark feature of cellular senescence and organ aging.Here,we asked whether the mitochondrial antiviral signaling protein(MAVS),which is essential for driving antiviral response,also regulates human stem cell senescence.To answer this question,we used CRISPR/Cas9-mediated gene editing and directed differentiation techniques to generate various MAVS-knockout human stem cell models.We found that human mesenchymal stem cells(hMSCs)were sensitive to MAVS deficiency,as manifested by accelerated senescence phenotypes.We uncovered that the role of MAVS in maintaining mitochondrial structural integrity and functional homeostasis depends on its interaction with the guanosine triphosphatase optic atrophy type 1(OPA1).Depletion of MAVS or OPA1 led to the dysfunction of mitochondria and cellular senescence,whereas replenishment of MAVS or OPA1 in MAVS-knockout hMSCs alleviated mitochondrial defects and premature senescence phenotypes.Taken together,our data underscore an uncanonical role of MAVS in safeguarding mitochondrial homeostasis and antagonizing human stem cell senescence.
查看更多>>摘要：Infectious diseases severely threaten public health and global biosafety.In addition to transmission through the air,pathogenic microorganisms have also been detected in environmental liquid samples,such as sewage water.Conventional biochemical detection methodologies are time-consuming and cost-ineffective,and their detection limits hinder early diagnosis.In the present study,ultrafine plasmonic fiber probes with a diameter of 125 μm are fabricated for clustered regularly interspaced short palindromic repeats/CRISPR-associated protein(CRISPR/Cas)-12a-mediated sensing of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Single-stranded DNA exposed on the fiber surface is trans-cleaved by the Cas12a enzyme to release gold nanoparticles that are immobilized onto the fiber surface,causing a sharp reduction in the surface plasmon resonance(SPR)wavelength.The proposed fiber probe is virus-specific with the limit of detection of～2,300 copies/ml,and genomic copy numbers can be reflected as shifts in wavelengths.A total of 21 sewage water samples have been examined,and the data obtained are consistent with those of quantitative polymerase chain reaction(qPCR).In addition,the Omicron variant and its mutation sites have been fast detected using S gene-specific Cas12a.This study provides an accurate and convenient approach for the real-time surveillance of microbial contamination in sewage water.
查看更多>>摘要：Flowing water can be used as an energy source for generators,providing a major part of the energy for daily life.However,water is rarely used for information or electronic devices.Herein,we present the feasibility of a polarized liquid-triggered photodetector in which polarized water is sandwiched between graphene and a semiconductor.Due to the polarization and depolarization processes of water molecules driven by photogenerated carriers,a photo-sensitive current can be repeatedly produced,resulting in a high-performance photodetector.The response wavelength of the photodetector can be fine-tuned as a result of the free choice of semiconductors as there is no requirement of lattice match between graphene and the semiconductors.Under zero voltage bias,the responsivity and specific detectivity of Gr/NaCl(0.5 M)W/N-GaN reach values of 130.7 mA/W and 2.3 x 109 Jones under 350 nm illumination,respectively.Meanwhile,using a polar liquid photodetector can successfully read the photoplethysmography signals to produce accurate oxygen blood saturation and heart rate.Compared with the commercial pulse oximetry sensor,the average errors of oxygen saturation and heart rate in the designed photoplethysmography sensor are～1.9％and～2.1％,respectively.This study reveals that water can be used as a high-performance photodetector in informative industries.
查看更多>>摘要：The cell-specific functions of nitric oxide(NO)in the intestinal microenvironment orchestrate its therapeutic effects in ulcerative colitis.While most biomaterials show promise by eliciting the characteristics of NO,the insufficient storage,burst release,and pro-inflammatory side effects of NO remain as challenges.Herein,we report the development of thiol-disulfide hybrid mesoporous organosilica nanoparticles(MONs)that improve the storage and sustained release of NO,broadening the therapeutic window of NO-based therapy against colitis.The tailored NO-storing nanomaterials coordinated the release of NO and the immunoregulator dexamethasone(Dex)in the intestinal microenvironment,specifically integrating the alleviation of oxidative stress in enterocytes and the reversal of NO-exacerbated macrophage activation.Mechanistically,such a synchronous operation was achieved by a self-motivated process wherein the thiyl radicals produced by NO release cleaved the disulfide bonds to degrade the matrix and release Dex via thiol-disulfide exchange.Specifically,the MON-mediated combination of NO and Dex greatly ameliorated intractable colitis compared with 5-aminosalicylic acid,even after delayed treatment.Together,our results reveal a key contribution of synergistic modulation of the intestinal microenvironment in NO-based colitis therapy and introduce thiol-disulfide hybrid nanotherapeutics for the management of inflammatory diseases and cancer.
查看更多>>摘要：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.
查看更多>>摘要：An optical spectrometer is a basic spectral instrument that probes microscopic physical and chemical properties of macroscopic objects but generally suffers from difficulty in broadband time-resolved measurement.In this work,we report the creation of ultrabroadband white-light laser with a 3-dB bandwidth covering 385 to 1,080 nm,pulse energy of 1.07 mJ,and pulse duration of several hundred femtoseconds by passing 3-mJ pulse energy,50-fs pulse duration Ti:Sapphire pulse laser through a cascaded fused silica plate and chirped periodically poled lithium niobate crystal.We utilize this unprecedented superflat,ultrabroadband,and intense femtosecond laser light source to build a single-shot(i.e.,single-pulse)subpicosecond pulse laser ultraviolet-visible-near-infrared spectrometer and successfully measure various atomic and molecular absorption spectra.The single-shot ultrafast spectrometer may open up a frontier to monitor simultaneously the ultrafast dynamics of multiple physical and chemical processes in various microscopic systems.
查看更多>>摘要：Soft carbons have attracted extensive interests as competitive anodes for fast-charging sodium-ion batteries(SIBs);however,the high-rate performance is still restricted by their large ion migration barriers and sluggish reaction kinetics.Herein,we show a molecular design approach toward the fabrication of nitrogen and phosphorus codoped mesoporous soft carbon(NPSC).The key to this strategy lies in the chemical cross-linking reaction between polyphosphoric acid and p-phenylenediamine,associated with pyrolysis induced in-situ self-activation that creates mesoporous structures and rich heteroatoms within the carbon matrix.Thanks to the enlarged interlayer spacing,reduced ion diffusion length,and plentiful active sites,the obtained NPSC delivers a superb rate capacity of 215 mAh g-1 at 10 A g-1 and an ultralong cycle life of 4,700 cycles at 5 A g-1.Remarkably,the full cell shows 99％capacity retention during 100 continuous cycles,and maximum energy and power densities of 191 Wh kg-1 and 9.2 kW kg-1,respectively.We believe that such a synthetic protocol could pave a novel venue to develop soft carbons with unique properties for advanced SIBs.
查看更多>>摘要：Black phosphorus gives several advantages and complementarities over other two-dimensional materials.It has drawn extensive interest owing to its relatively high carrier mobility,wide tunable bandgap,and in-plane anisotropy in recent years.This manuscript briefly reviews the structure and physical properties of black phosphorus and targets on black phosphorus for photonic integrated circuits.Some of the applications are discussed including photodetection,optical modulation,light emission,and polarization conversion.Corresponding recent progresses,associated challenges,and future potentials are covered.
查看更多>>摘要：Primary sclerosing cholangitis(PSC)is a biliary disease accompanied by chronic inflammation of the liver and biliary stricture.Mesenchymal stem cells(MSCs)are used to treat liver diseases because of their immune regulation and regeneration-promoting functions.This study was performed to explore the therapeutic potential of human placental MSCs(hP-MSCs)in PSC through the Takeda G protein-coupled receptor 5(TGR5)receptor pathway.Liver tissues were collected from patients with PSC and healthy donors(n=4)for RNA sequencing and intrahepatic cholangiocyte organoid construction.hP-MSCs were injected via the tail vein into Mdr2-/-,bile duct ligation(BDL),and 3,5-diethoxycarbony l-1,4-dihydrocollidine(DDC)mouse models or co-cultured with organoids to confirm their therapeutic effect on biliary cholangitis.Changes in bile acid metabolic profile were analyzed by liquid chromatography/tandem mass spectrometry(LC-MS/MS).Compared with healthy controls,liver tissues and intrahepatic cholangiocyte organoids from PSC patients were characterized by inflammation and cholestasis,and marked downregulation of bile acid receptor TGR5 expression.hP-MSC treatment apparently reduced the inflammation,cholestasis,and fibrosis in Mdr2-/-,BDL,and DDC model mice.By activating the phosphatidylinositol 3 kinase/extracellular signal-regulated protein kinase pathway,hP-MSC treatment promoted the proliferation of cholangiocytes,and affected the transcription of downstream nuclear factor κB through regulation of the binding of TGR5 and Pellino3,thereby affecting the cholangiocyte inflammatory phenotype.
查看更多>>摘要：Neddylation is necessary for activation of Cullin-RING ligases(CRLs),which degrade various immune regulatory proteins.Our recent study showed that while depletion of neddylation E2-E3 pair Ube2f-Sag in regulatory T(Treg)cells had no obvious phenotype,the same depletion of either Ube2m or Rbx1 caused inflammation disorders with different severity.Whether these E2s or E3s compensate each other in functional regulations of Treg cells is,however,previously unknown.In this report,we generated Foxp3Cre;Ube2mfl/fl;Ube2ffl/fl or Foxp3Cre;Rbx1fl/fl;Sagfl/fl double-null mice by simultaneous deletion of both neddylation E2s or E3s in Treg cells,respectively.Remarkably,Ube2m&Ube2f double-null mice developed much severe autoimmune phenotypes than did Ube2m-null mice,indicating that Ube2m markedly compensates Ube2f in Treg cells.The minor worsened autoimmune phenotypes seen at the very early stage in Rbx1&Sag double-null than Rbx1-nu ll mice is likely due to already severe phenotypes of the later,indicating a minor compensation of Rbx1 for Sag.The RNA profiling-based analyses revealed that up-and down-regulations of few signaling pathways in Treg cells are associated with the severity of autoimmune phenotypes.Finally,severer inflammation phenotypes seen in mice with double E3-null than with double E2-null Treg cells indicate a neddylation-independent mechanism of 2 E3s,also known to serve as the RING component of CRLs in regulation of Treg cell fitness.
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