Symmetric Na-ion cells using the NASICON-structured electrodes could simplify the manufacturing process,reduce the cost,facilitate the recycling post-process,and thus attractive in the field of large-scale stationary ...Symmetric Na-ion cells using the NASICON-structured electrodes could simplify the manufacturing process,reduce the cost,facilitate the recycling post-process,and thus attractive in the field of large-scale stationary energy storage.However,the long-term cycling performance of such batteries is usually poor.This investigation reveals the unavoidable side reactions between the NASICON-type Na_(3)V_(2)(PO_(4))_(3)(NVP)anode and the commercial liquid electrolyte,leading to serious capacity fading in the symmetric NVP//NVP cells.To resolve this issue,an all-solid-state composite electrolyte is used to replace the liquid electrolyte so that to overcome the side reaction and achieve high anode/electrolyte interfacial stability.The ferroelectric engineering could further improve the interfacial ion conduction,effectively reducing the electrode/electrolyte interfacial resistances.The NVP//NVP cell using the ferroelectric-engineered composite electrolyte can achieve a capacity retention of 86.4%after 650 cycles.Furthermore,the electrolyte can also be used to match the Prussianblue cathode NaxFeyFe(CN)_(6−z)·nH_(2)O(NFFCN).Outstanding long-term cycling stability has been obtained in the all-solid-state NVP//NFFCN cell over 9000 cycles at a current density of 500 mA g^(-1),with a fading rate as low as 0.005%per cycle.展开更多
Aerosol deposition(AD)method is a kind of additive manufacturing technology for fabricating dense films such as metals and ceramics at room temperature.It resolves the challenge of integrating ceramic films onto tempe...Aerosol deposition(AD)method is a kind of additive manufacturing technology for fabricating dense films such as metals and ceramics at room temperature.It resolves the challenge of integrating ceramic films onto temperaturesensitive substrates,including metals,glasses,and polymers.It should be emphasized that the AD is a spray coating technology that uses powder without thermal assistance to generate films with high density.Compared to the traditional sputter-based approach,the AD shows several advantages in efficiency,convenience,better interfacial bonding and so on.Therefore,it opens some possibilities to the field of batteries,especially all-solidstate batteries(ASSBs)and draws much attention not only for research but also for large scale applications.The purpose of this work is to provide a critical review on the science and technology of AD as well as its applications in the field of batteries.The process,mechanism and effective parameters of AD,and recent developments in AD applications in the field of batteries will be systematically reviewed so that a trend for AD will be finally provided.展开更多
We perform ^(23)Na nuclear magnetic resonance(NMR) and magnetization measurements on an S=1,quasi-2D honeycomb lattice antiferromagnet Na_(3)Ni_(2)BiO_(6).A large positive Curie-Weiss constant of 22.9 K is observed.Th...We perform ^(23)Na nuclear magnetic resonance(NMR) and magnetization measurements on an S=1,quasi-2D honeycomb lattice antiferromagnet Na_(3)Ni_(2)BiO_(6).A large positive Curie-Weiss constant of 22.9 K is observed.The NMR spectra at low fields are consistent with a zigzag magnetic order,indicating a large easy-axis anisotropy.With the field applied along the c*axis,the NMR spectra confirm the existence of a 1/3-magnetization plateau phase between 5.1 T and 7.1 T.The transition from the zigzag order to the 1/3-magnetization plateau phase is also found to be a first-order type.A monotonic decrease of the spin gap is revealed in the 1/3-magnetization plateau phase,which reaches zero at a quantum critical field H_(C)≈8.35 T before entering the fully polarized phase.These data suggest the existence of exchange frustration in the system along with strong ferromagnetic interactions,hosting the possibility for Kitaev physics.Besides,well below the ordered phase,the 1/T_(1) at high fields shows either a level off or an enhancement upon cooling below 3 K,which suggests the existence of low-energy fluctuations.展开更多
Bolts are important fasteners indispensable in the manufacturing field for their advantages, which include convenient assembly and disassembly, easy maintenance, refastenability to prevent looseness, and the avoidance...Bolts are important fasteners indispensable in the manufacturing field for their advantages, which include convenient assembly and disassembly, easy maintenance, refastenability to prevent looseness, and the avoidance of a phase change in the connected material composition. The precise control of the tightening force in bolts is closely related to the safety and reliability of the connected equipment or structure. Although there are many methods for estimating the tightening force applied to a bolt during assembly, poor accuracy in controlling the preload during the tightening process and a lack of monitoring to determine the residual axial force in service remain issues in evaluating the safety of bolted assemblies. As a nondestructive testing technology, ultrasonic measurement can be applied to successfully address these issues. In order to help researchers understand the theoretical basis and technological development in this field and to equip them to conduct further in-depth research, in this review, the basic knowledge describing the state of stress and deformation of bolts, as well as conventional testing methods are summarized and analyzed. Then, through a review of recent research of the ultrasonic measurement of the axial stress in bolts, the influence of the e ective stressed length and temperature are analyzed and proposed methods of calibration and compensation are reviewed. In order to avoid coupling errors caused by traditional piezoelectric transducers, two newly proposed ultrasonic coupling technologies, the electromagnetic acoustic transducer(EMAT) and the permanent mounted transducer system(PMTS), are reviewed. Finally, the new direction of research of the detection of residual axial stress in in-service bolts that have been assembled to yield is discussed.展开更多
Hypoxia is a typical feature of solid tumors,which highly limits the application of the oxygen-dependent therapy.Also,the dense and hyperbaric tumor tissues impede the penetration of nanoparticles into the deep tumor....Hypoxia is a typical feature of solid tumors,which highly limits the application of the oxygen-dependent therapy.Also,the dense and hyperbaric tumor tissues impede the penetration of nanoparticles into the deep tumor.Thereby,we designed a novel localized injectable hydrogel combining the photothermal therapy(PTT)and the thermodynamic therapy(TDT),which is based on the generation of free radicals even in the absence of oxygen for hypoxic tumor therapy.In our study,gold nanorods(Au NRs)and 2,2-Azobis[2-(2-imidazalin-2-yl)propane]dihydrochlaride(AIPH)were incorporated into the hydrogel networks,which were formed by the copolymerization of hydrophobic N-isopropyl acrylamide(NIPAM)and hydrophilic glycidyl methacrylate modified hyaluronic acid(HAGMA)to fabricate an injectable and near-infrared(NIR)responsive hydrogel.The crosslinked in situ forming hydrogel could not only realize PTT upon the NIR laser irradiation,but also generate free radicals even in hypoxic condition.Meanwhile the shrink of hydrogels upon thermal could accelerate the generation of free radicals to further damage the tumors,achieving the controlled drug release on demand.The designed hydrogel with a sufficient loading capacity,excellent biocompatibility and negligible systemic toxicity could serve as a long-acting implant for NIR-triggered thermo-responsive free radical generation.The in vitro cytotoxicity result and the in vivo antitumor activity illustrated the excellent therapeutic effect of hydrogels even in the absence of oxygen.Therefore,this innovative oxygen-independent platform combining the antitumor effects of PTT and TDT would bring a new insight into hypoxic tumor therapy by the application of alkyl free radical.展开更多
Cannabis sativa is a well-known plant species that has great economic and ecological significance.An incomplete genome of cloned C.sativa was obtained by using SOAPdenovo software in 2011.To further explore the utiliz...Cannabis sativa is a well-known plant species that has great economic and ecological significance.An incomplete genome of cloned C.sativa was obtained by using SOAPdenovo software in 2011.To further explore the utilization of this plant resource,we generated an updated draft genome sequence for wild-type varieties of C.sativa in China using PacBio single-molecule sequencing and Hi-C technology.Our assembled genome is approximately 808 Mb,with scaffold and contig N50 sizes of 83.00 Mb and 513.57 kb,respectively.Repetitive elements account for 74.75%of the genome.A total of 38,828 protein-coding genes were annotated,98.20%of which were functionally annotated.We provide the first comprehensive de novo genome of wild-type varieties of C.sativa distributed in Tibet,China.Due to long-term growth in the wild environment,these varieties exhibit higher heterozygosity and contain more genetic information.This genetic resource is of great value for future investigations of cannabinoid metabolic pathways and will aid in promoting the commercial production of C.sativa and the effective utilization of cannabinoids.The assembled genome is also a valuable resource for intensively and effectively investigating the C.sativa genome further in the future.展开更多
Eavesdropping attacks have become one of the most common attacks on networks because of their easy implementation. Eavesdropping attacks not only lead to transmission data leakage but also develop into other more harm...Eavesdropping attacks have become one of the most common attacks on networks because of their easy implementation. Eavesdropping attacks not only lead to transmission data leakage but also develop into other more harmful attacks. Routing randomization is a relevant research direction for moving target defense, which has been proven to be an effective method to resist eavesdropping attacks. To counter eavesdropping attacks, in this study, we analyzed the existing routing randomization methods and found that their security and usability need to be further improved. According to the characteristics of eavesdropping attacks, which are “latent and transferable”, a routing randomization defense method based on deep reinforcement learning is proposed. The proposed method realizes routing randomization on packet-level granularity using programmable switches. To improve the security and quality of service of legitimate services in networks, we use the deep deterministic policy gradient to generate random routing schemes with support from powerful network state awareness. In-band network telemetry provides real-time, accurate, and comprehensive network state awareness for the proposed method. Various experiments show that compared with other typical routing randomization defense methods, the proposed method has obvious advantages in security and usability against eavesdropping attacks.展开更多
Photodynamic therapy(PDT)-mediated oxidation treatment is extremely attractive for skin melanoma ablation,but the strong hydrophobicity and poor tumor selectivity of photosensitizers,as well as the oxygen-consuming pr...Photodynamic therapy(PDT)-mediated oxidation treatment is extremely attractive for skin melanoma ablation,but the strong hydrophobicity and poor tumor selectivity of photosensitizers,as well as the oxygen-consuming properties of PDT,leading to unsatisfactory therapeutic outcomes.Herein,a tumor acidic microenvironment activatable dissolving microneedle(DHA@HPFe-MN)was developed to realize controlled drug release and excellent chemo-photodynamic therapy of melanoma via oxidative stress amplification.The versatile DHA@HPFe-MN was fabricated by crosslinking a self-synthesized protoporphyrin(PpIX)-ADH-hyaluronic acid(HA)conjugate HA-ADH-PpIX with“iron reservoir”PA-Fe 3+complex in the needle tip via acylhydrazone bond formation,and dihydroartemisinin(DHA)was concurrently loaded in the hydrogel network.HA-ADH-PpIX with improved water solubility averted undesired aggregation of PpIX to ensure enhanced PDT effect.DHA@HPFe-MN with sharp needle tip,efficient drug loading and excellent mechanical strength could efficiently inserted into skin and reach the melanoma sites,where the acidic pH triggered the degradation of microneedles,enabling Fe-activated and DHA-mediated oxidation treatment,as evidenced by abundant reactive oxygen species(ROS)generation.Moreover,under light irradiation,a combined chemo-photodynamic therapeutic effect was achieved with amplified ROS generation.Importantly,the Fe-catalyzed ROS production of DHA was oxygen-independent,which work in synergy with the oxygen-dependent PDT to effectively destroy tumor cells.This versatile microneedles with excellent biosafety and biodegradability can be customized as a promising localized drug delivery system for combined chemo-photodynamic therapy of melanoma.展开更多
Purpose:To report an unusual case of idiopathic orbital inflammation associated with panuveitis. Case report:We report a case of a 47-year-old female with a history of uveitis who presented with abrupt and painful pro...Purpose:To report an unusual case of idiopathic orbital inflammation associated with panuveitis. Case report:We report a case of a 47-year-old female with a history of uveitis who presented with abrupt and painful prop tosis with complete vision loss unresponsive to antibiotic therapy.B-scan ultrasonography and magnetic resonance imaging both showed retinal detachment and an orbital space-occupying mass. The patient underwent orbitotomy and the diagnosis of idiopathic orbital inflammation was confirmed by histopathology. Anterior uveitis is rarely seen in idiopathic orbital inflammation in adults. We report for the first time an unusual case of idiopathic orbital inflammation associated with panuveitis. Conclusion:Inflammation involving both the eye and the orbit is rarely seen in adults. Idiopathic orbital inflammation and panuveitis may share a similar mechanism in this case. (Eye Science 2013; 28:40-43)展开更多
AIM To assess the effects of probiotic Medilac-S~ as adjunctive therapy for the induction of remission of ulcerative colitis(UC) in a Chinese population through a systematic review and meta-analysis. METHODS A syste...AIM To assess the effects of probiotic Medilac-S~ as adjunctive therapy for the induction of remission of ulcerative colitis(UC) in a Chinese population through a systematic review and meta-analysis. METHODS A systematic literature search was conducted to find randomized, controlled trials in a Chinese population with at least two study arms-a control arm which receives a conventional, oral aminosalicylate drug, and a treatment arm, which administers the same conventional drug in conjunction with the probiotic Medilac-S~ per os. Both English and Chinese databases were searched, including Pub Med, EMBASE, Google Scholar, Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Search, and study data was extracted onto standardized abstraction sheets. Meta-analyses were conducted for primary and secondary outcomes of interest using a fixed or random effects model. The primary outcome was the induction of clinical remission and the secondary outcomes included changes in Sutherland index, endoscopic and histological scores, proportion of reported clinical symptoms and adverse events(AEs). For outcomes with sufficient data, the type of conventional drug therapy was also assessed to determine if the effects of combination therapy with Medilac-S~ was influenced by drug type. All tests were conducted using a type Ⅰ error rate of 0.05 and all confidence intervals(CI) were based on a 95% confidence level. Review protocol was uploaded to PROSPERO(CRD42018085658 upon completion).RESULTS Fifty-three clinical trials with a total of 3984 participants were identified and included in the review. Medilac-S~ adjunctive therapy significantly improved induction of clinical remission(RR = 1.21; 95%CI: 1.18-1.24; P < 0.0001) with the estimated likelihood of effective treatment, on average, 21% higher for those consuming the probiotic. Sutherland index scores showed the control mean was on average 3.10(CI: 2.41-3.78; P = 0.0428) units greater than the treatment mean, thereby demonstrating significant improvement in participants taking the probiotic. Similarly, a significant difference was seen between the overall reduction of endoscopic and histological scores of control and treatment arm participants, with score decreases in the control groups 0.71(CI: 0.3537-1.0742) and 1.1(CI: 0.9189-1.2300) units smaller than treatment group score decreases. The proportion of participants reporting clinical symptoms,(abdominal pain, tenesmus, blood and mucous in stool, and diarrhea) was significantly reduced after combination therapy with Medilac-S~(P < 0.0001) and estimated to be on average 44%(RR = 0.44, CI: 0.32-0.59), 53%(RR = 0.53, CI: 0.38-74), 40%(RR = 0.40, CI: 0.28-0.58) and 47%(RR = 0.47 CI: 0.36-0.42) respectively, of the proportion of individuals reporting the aforementioned symptoms after conventional therapy alone. The risk of AEs was also significantly reduced with adjunctive Medilac-S~ therapy. The proportion of individuals in the treatment groups reporting AEs was an estimated 72% of the proportion of individuals in the control groups reporting AEs(RR = 0.72, CI: 0.55-0.94, P = 0.0175). Upon comparing effect means for different drug types in conjunction with Medilac-S~, evidence of significant variability(P < 0.0001) was observed, and sulfasalazine was found to be the most effective drug in both primary and secondary outcomes. CONCLUSION Evidence suggests Medilac-S~ adjunctive therapy should be considered standard care for UC in a Chinese population because it aids in the induction of clinical remission, improves symptoms of the gastrointestinal tract and reduces risk of AEs.展开更多
The solid-state electrolyte in a solid-state battery acts as an electrons'barrier and an ions'bridge between the two electrodes.As solid-state electrolyte does not store the mobile ions,it is necessary to achi...The solid-state electrolyte in a solid-state battery acts as an electrons'barrier and an ions'bridge between the two electrodes.As solid-state electrolyte does not store the mobile ions,it is necessary to achieve a thin solid-state electrolyte to reduce the internal resistance and enhance the energy density.In this work,a thin NASICON solid-state electrolyte,with a stoichiometry of Na_(3)Zr_(2)Si_(2)PO_(12),is fabricated by the tape-casting method and its thickness can be easily controlled by the gap between substrate and scraper.The areal-specific resistance and the flexural strength increase with the electrolyte thickness.A solid-state sodium metal battery with 86 pm thick Na_(3)Zr_(2)Si_(2)PO_(12)exhibits a reversible specific capacity of 73-78 mAh g^(-1)with a redox potential of 3.4 V at 0.2 C.This work presents the importance of electrolyte thickness to reduce internal resistance and achieve a high energy density for sodium batteries.展开更多
Posterior capsular opacification(PCO)is the leading cause of vision loss after cataract,mainly caused by the adhesion,proliferation and trans-differentiation of post-operative residual lens epithelial cells(LECs).Effe...Posterior capsular opacification(PCO)is the leading cause of vision loss after cataract,mainly caused by the adhesion,proliferation and trans-differentiation of post-operative residual lens epithelial cells(LECs).Effective PCO prevention remains a huge challenge to ophthalmologists and researches for decades.Herein,we developed a“NIR-triggered ROS storage”intraocular implant(CTR-Py-Pp IX)based on capsular tension ring(CTR),which is concurrently linked with photosensitizer protophorphyrin IX(Pp IX)and energy storage2-pyridone derivative(Py),to guarantee instantaneous and sustainable ROS generation for LECs killing,aiming to achieve more efficient and safer photodynamic therapy(PDT)to effectively prevent PCO.The silylated Pp IX-Si and Py-Si were covalently conjugated to the plasma activated CTR surface to obtain CTR-Py-Pp IX.Results demonstrated that CTR-Py-Pp IX had dual functions of PDT and battery,in which Pp IX could generate ROS extracellularly under irradiation,with one part directly inhibiting LECs by lipid peroxidation(LPO)induction of cell membranes.Meanwhile,the excess ROS stored in Py could be continuously released to amplify LPO levels after the irradiation was removed.Ultimately,the proliferation of LECs in capsular bag was completely inhibited under mild irradiation conditions,achieving a sustainable and controlled PDT effect for effective PCO prevention with good biocompatibility.This NIR-triggered ROS storage intraocular implant would provide a more efficient and safer approach for long-term PCO prevention.展开更多
The evolution of light-skin pigmentation among Eurasians is considered as an adaptation to the high-latitude environments.East Asians are ideal populations for studying skin color evolution because of the complex envi...The evolution of light-skin pigmentation among Eurasians is considered as an adaptation to the high-latitude environments.East Asians are ideal populations for studying skin color evolution because of the complex environment of East Asia.Here,we report a strong selection signal for the pigmentation gene phenylalanine hydroxylase(PAH)in light-skinned Han Chinese individuals.The intron mutation rs10778203 in PAH is enriched in East Asians and is significantly associated with skin color of the back of the hand in Han Chinese males(P<0.05).In vitro luciferase and transcription factor binding assays show that the ancestral allele of rs10778203 could bind to SMAD2 and has a significant enhancer activity for PAH.However,the derived T allele(the major allele in East Asians)of rs10778203 decreases the binding activity of transcription factors and enhancer activity.Meanwhile,the derived T allele of rs10778203 shows a weaker ultraviolet radiation response in A375 cells and zebrafish embryos.Furthermore,rs10778203 decreases melanin production in transgenic zebrafish embryos after ultraviolet B(UVB)treatment.Collectively,PAH is a potential pigmentation gene that regulates skin tanning ability.Natural selection has enriched the adaptive allele,resulting in weakened tanning ability in East Asians,suggesting a unique genetic mechanism for evolutionary skin lightening in East Asians.展开更多
Polyimide(PI)has emerged as a promising organic photocatalyst owing to its distinct advantages of high visible-light response,facile synthesis,molecularly tunable donor-acceptor structure,and excellent physicochemical...Polyimide(PI)has emerged as a promising organic photocatalyst owing to its distinct advantages of high visible-light response,facile synthesis,molecularly tunable donor-acceptor structure,and excellent physicochemical stability.However,the synthesis of high-quality PI photoelectrode remains a challenge,and photoelectrochemical(PEC)water splitting for PI has been less studied.Herein,the synthesis of uniform PI photoelectrode films via a simple spin-coating method was reported,and their PEC properties were investigated using melamine as donor and various anhydrides as acceptors.The influence of the conjugate size of aromatic unit(phenyl,biphenyl,naphthalene,perylene)of electron acceptor on PEC performance were studied,where naphthalene-based PI photoelectrode exhibited the highest photocurrent response.This is resulted from the unification of widerange light absorption,efficient charge separation and transport,and strong photooxidation capacity.This paper expands the material library of polymer films for PEC applications and contributes to the rational design of efficient polymer photoelectrodes.展开更多
In more than 200 years since Edward Jenner successfully developed the first vaccine for combating smallpox,vaccines have played pivotal roles in preventing outbreaks of several infectious diseases,and it could even be...In more than 200 years since Edward Jenner successfully developed the first vaccine for combating smallpox,vaccines have played pivotal roles in preventing outbreaks of several infectious diseases,and it could even be asserted that each one of us has benefited from them.The recent severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)outbreak has also demonstrated the importance of vaccines in interrupting the transmission of infectious diseases(Deng and Peng,2020).展开更多
Interleukin-6(IL-6)is a common pluripotent cytokine that is highly expressed in the tumor microenvironment.The IL-6/JAK/STAT3 signaling directly promotes tumor progression,severely hampering antitumor immunity.Macroph...Interleukin-6(IL-6)is a common pluripotent cytokine that is highly expressed in the tumor microenvironment.The IL-6/JAK/STAT3 signaling directly promotes tumor progression,severely hampering antitumor immunity.Macrophages,the richest innate immune cells within the tumor microenvironment,manipulate tumor progression via phenotypic plasticity.展开更多
Dominant optic atrophy(DOA)is an inherited optic neuropathy and more than 75%of DOA patients harbor pathogenic mutations in OPA1.We reported a 39-year-old female harboring c.2119G>T mutation of OPA1 and manifested ...Dominant optic atrophy(DOA)is an inherited optic neuropathy and more than 75%of DOA patients harbor pathogenic mutations in OPA1.We reported a 39-year-old female harboring c.2119G>T mutation of OPA1 and manifested progressive visual impairment after hydroxychloroquine(HCQ)therapy.The patient’s visual impairment remained stable for 10 years until she began to take HCQ 13 months ago.She complained about progressively decreased vision in both eyes.Bilateral pale temporal optic disc was similar with that of 11 years ago.Optical coherence tomography showed bilateral moderate retinal nerve fiber layer thinning other than the nasal quadrant and general thinning of the inner retina in the macular.Microcystic macular edema was noted in nasal macular in both eyes.Visual field testing showed paracentral scotoma and microperimetry showed decrease sensitivity in the macular in both eyes.After the patient stopped taking HCQ,her functional tests including visual acuity,field testing and microperimetry testing was stable compared with those of 2 years ago.However,progressive inner macular and RNFL thinning was shown by OCT.OPA1 c.2119 G>T found in this patient was a mutation that had been rarely reported in previous studies.The patient has been followed up for over 10 years and her visual acuity stayed stable for decades long until she took HCQ for 13 months.Her vision decline terminated after she stopped taking HCQ.Although HCQ toxicity is highly related to the duration and daily dose,HCQ may aggravate visual impairment in certain individuals harboring OPA1 mutation.Patients with DOA should avoid using neurotoxic HCQ and other medications that may interfere mitochondrial metabolism.展开更多
Bladder cancer is one of the concerning malignancies worldwide,which is lacking effective targeted therapy.Gene therapy is a potential approach for bladder cancer treatment.While,a safe and effective targeted gene del...Bladder cancer is one of the concerning malignancies worldwide,which is lacking effective targeted therapy.Gene therapy is a potential approach for bladder cancer treatment.While,a safe and effective targeted gene delivery system is urgently needed for prompting the bladder cancer treatment in vivo.In this study,we confirmed that the bladder cancer had CD44 overexpression and small interfering RNAs(siRNA)with high interfere to Bcl2 oncogene were designed and screened.Then hyaluronic acid dialdehyde(HAD)was prepared in an ethanol-water mixture and covalently conjugated to the chitosan nanoparticles(CS-HAD NPs)to achieve CD44 targeted siRNA delivery.The in vitro and in vivo evaluations indicated that the siRNA-loaded CS-HAD NPs(siRNA@CS-HAD NPs)were approximately 100 nm in size,with improved stability,high siRNA encapsulation efficiency and low cytotoxicity.CS-HAD NPs could target to CD44 receptor and deliver the therapeutic siRNA into T24 bladder cancer cells through a ligand-receptor-mediated targeting mechanism and had a specific accumulation capacity in vivo to interfere the targeted oncogene Bcl2 in bladder cancer.Overall,a CD44 targeted gene delivery system based on natural macromolecules was developed for effective bladder cancer treatment,which could be more conducive to clinical application due to its simple preparation and high biological safety.展开更多
A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry(UPLC–MS/MS) method was developed and fully validated for determination of arformoterol in rat plasma, lung and trachea tissues....A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry(UPLC–MS/MS) method was developed and fully validated for determination of arformoterol in rat plasma, lung and trachea tissues. The chromatographic separation was performed on an Agilent XDB C8 column with gradient elution by using acetonitrile and 0.1% formic acid water. The method presented high sensitivity(LLOQ of 1.83 pg/mL for plasma and 3.90 pg/mL for lung and trachea tissue homogenates) and great linearity over the range of 1.83–458 pg/mL for plasma, 13.9–1560 pg/mL for lung and trachea tissue homogenates. No carry over effect and matrix effect were observed. The intra-and inter-day precision/accuracy were within ±15% at three quality control concentration levels. This robust method was successfully applied to the pharmacokinetic, lung and trachea tissue distribution study after inhalation administration of arformoterol tartrate inhalation solution(50 m g/kg). The in vivo information indicate that arformoterol can be rapidly absorbed into blood through respiratory systems, lung and trachea tissue maintain a certain amount of arformoterol in 1 h after dosing.展开更多
基金supported by the National University of Singapore(Chongqing)Research Institute,National University of Singapore,Chongqing Postdoctoral Research Special Funding(2021XM2002)Overseas Postdoctoral Research Start-up Funding,Natural Science Foundation of Chongqing(cstc2021jcyjmsxmX0086)+1 种基金Chongqing Innovative Project for oversea-experience researchers(cx2023037)the Open Project Program of Fujian Key Laboratory of Special Energy Manufacturing.
文摘Symmetric Na-ion cells using the NASICON-structured electrodes could simplify the manufacturing process,reduce the cost,facilitate the recycling post-process,and thus attractive in the field of large-scale stationary energy storage.However,the long-term cycling performance of such batteries is usually poor.This investigation reveals the unavoidable side reactions between the NASICON-type Na_(3)V_(2)(PO_(4))_(3)(NVP)anode and the commercial liquid electrolyte,leading to serious capacity fading in the symmetric NVP//NVP cells.To resolve this issue,an all-solid-state composite electrolyte is used to replace the liquid electrolyte so that to overcome the side reaction and achieve high anode/electrolyte interfacial stability.The ferroelectric engineering could further improve the interfacial ion conduction,effectively reducing the electrode/electrolyte interfacial resistances.The NVP//NVP cell using the ferroelectric-engineered composite electrolyte can achieve a capacity retention of 86.4%after 650 cycles.Furthermore,the electrolyte can also be used to match the Prussianblue cathode NaxFeyFe(CN)_(6−z)·nH_(2)O(NFFCN).Outstanding long-term cycling stability has been obtained in the all-solid-state NVP//NFFCN cell over 9000 cycles at a current density of 500 mA g^(-1),with a fading rate as low as 0.005%per cycle.
基金supported by National University of Singapore (Chongqing) Research InstituteNational University of Singapore+2 种基金Chongqing Postdoctoral Research Special FundingOverseas Postdoctoral Research Start-up FundingNatural Science Foundation of Chongqing, China (cstc2021jcyj-msxmX0086)
文摘Aerosol deposition(AD)method is a kind of additive manufacturing technology for fabricating dense films such as metals and ceramics at room temperature.It resolves the challenge of integrating ceramic films onto temperaturesensitive substrates,including metals,glasses,and polymers.It should be emphasized that the AD is a spray coating technology that uses powder without thermal assistance to generate films with high density.Compared to the traditional sputter-based approach,the AD shows several advantages in efficiency,convenience,better interfacial bonding and so on.Therefore,it opens some possibilities to the field of batteries,especially all-solidstate batteries(ASSBs)and draws much attention not only for research but also for large scale applications.The purpose of this work is to provide a critical review on the science and technology of AD as well as its applications in the field of batteries.The process,mechanism and effective parameters of AD,and recent developments in AD applications in the field of batteries will be systematically reviewed so that a trend for AD will be finally provided.
基金Project supported by the National Key R&D Program of China (Grant Nos. 2023YFA1406500, 2022YFA1402700, and 2021YFA1400400)the National Natural Science Foundation of China (Grant Nos. 12134020, 12374156, 12104503,12061131004, 12225407, and 12074174)。
文摘We perform ^(23)Na nuclear magnetic resonance(NMR) and magnetization measurements on an S=1,quasi-2D honeycomb lattice antiferromagnet Na_(3)Ni_(2)BiO_(6).A large positive Curie-Weiss constant of 22.9 K is observed.The NMR spectra at low fields are consistent with a zigzag magnetic order,indicating a large easy-axis anisotropy.With the field applied along the c*axis,the NMR spectra confirm the existence of a 1/3-magnetization plateau phase between 5.1 T and 7.1 T.The transition from the zigzag order to the 1/3-magnetization plateau phase is also found to be a first-order type.A monotonic decrease of the spin gap is revealed in the 1/3-magnetization plateau phase,which reaches zero at a quantum critical field H_(C)≈8.35 T before entering the fully polarized phase.These data suggest the existence of exchange frustration in the system along with strong ferromagnetic interactions,hosting the possibility for Kitaev physics.Besides,well below the ordered phase,the 1/T_(1) at high fields shows either a level off or an enhancement upon cooling below 3 K,which suggests the existence of low-energy fluctuations.
基金Supported by Project of Basic Technology Research which is funded by Technology and Quality Division of the Ministry of Industry and Information Technology(Grant No.JSZL2017602B002).
文摘Bolts are important fasteners indispensable in the manufacturing field for their advantages, which include convenient assembly and disassembly, easy maintenance, refastenability to prevent looseness, and the avoidance of a phase change in the connected material composition. The precise control of the tightening force in bolts is closely related to the safety and reliability of the connected equipment or structure. Although there are many methods for estimating the tightening force applied to a bolt during assembly, poor accuracy in controlling the preload during the tightening process and a lack of monitoring to determine the residual axial force in service remain issues in evaluating the safety of bolted assemblies. As a nondestructive testing technology, ultrasonic measurement can be applied to successfully address these issues. In order to help researchers understand the theoretical basis and technological development in this field and to equip them to conduct further in-depth research, in this review, the basic knowledge describing the state of stress and deformation of bolts, as well as conventional testing methods are summarized and analyzed. Then, through a review of recent research of the ultrasonic measurement of the axial stress in bolts, the influence of the e ective stressed length and temperature are analyzed and proposed methods of calibration and compensation are reviewed. In order to avoid coupling errors caused by traditional piezoelectric transducers, two newly proposed ultrasonic coupling technologies, the electromagnetic acoustic transducer(EMAT) and the permanent mounted transducer system(PMTS), are reviewed. Finally, the new direction of research of the detection of residual axial stress in in-service bolts that have been assembled to yield is discussed.
基金supported by the National Natural Science Foundation of China(Grant number:81673369/H3008)Science and Technology Program of Guangzhou,China(Grant number:201604020157)。
文摘Hypoxia is a typical feature of solid tumors,which highly limits the application of the oxygen-dependent therapy.Also,the dense and hyperbaric tumor tissues impede the penetration of nanoparticles into the deep tumor.Thereby,we designed a novel localized injectable hydrogel combining the photothermal therapy(PTT)and the thermodynamic therapy(TDT),which is based on the generation of free radicals even in the absence of oxygen for hypoxic tumor therapy.In our study,gold nanorods(Au NRs)and 2,2-Azobis[2-(2-imidazalin-2-yl)propane]dihydrochlaride(AIPH)were incorporated into the hydrogel networks,which were formed by the copolymerization of hydrophobic N-isopropyl acrylamide(NIPAM)and hydrophilic glycidyl methacrylate modified hyaluronic acid(HAGMA)to fabricate an injectable and near-infrared(NIR)responsive hydrogel.The crosslinked in situ forming hydrogel could not only realize PTT upon the NIR laser irradiation,but also generate free radicals even in hypoxic condition.Meanwhile the shrink of hydrogels upon thermal could accelerate the generation of free radicals to further damage the tumors,achieving the controlled drug release on demand.The designed hydrogel with a sufficient loading capacity,excellent biocompatibility and negligible systemic toxicity could serve as a long-acting implant for NIR-triggered thermo-responsive free radical generation.The in vitro cytotoxicity result and the in vivo antitumor activity illustrated the excellent therapeutic effect of hydrogels even in the absence of oxygen.Therefore,this innovative oxygen-independent platform combining the antitumor effects of PTT and TDT would bring a new insight into hypoxic tumor therapy by the application of alkyl free radical.
基金The National Key R&D Program of China(Grant 2018YFC0807401)provided financial support for this study.
文摘Cannabis sativa is a well-known plant species that has great economic and ecological significance.An incomplete genome of cloned C.sativa was obtained by using SOAPdenovo software in 2011.To further explore the utilization of this plant resource,we generated an updated draft genome sequence for wild-type varieties of C.sativa in China using PacBio single-molecule sequencing and Hi-C technology.Our assembled genome is approximately 808 Mb,with scaffold and contig N50 sizes of 83.00 Mb and 513.57 kb,respectively.Repetitive elements account for 74.75%of the genome.A total of 38,828 protein-coding genes were annotated,98.20%of which were functionally annotated.We provide the first comprehensive de novo genome of wild-type varieties of C.sativa distributed in Tibet,China.Due to long-term growth in the wild environment,these varieties exhibit higher heterozygosity and contain more genetic information.This genetic resource is of great value for future investigations of cannabinoid metabolic pathways and will aid in promoting the commercial production of C.sativa and the effective utilization of cannabinoids.The assembled genome is also a valuable resource for intensively and effectively investigating the C.sativa genome further in the future.
文摘Eavesdropping attacks have become one of the most common attacks on networks because of their easy implementation. Eavesdropping attacks not only lead to transmission data leakage but also develop into other more harmful attacks. Routing randomization is a relevant research direction for moving target defense, which has been proven to be an effective method to resist eavesdropping attacks. To counter eavesdropping attacks, in this study, we analyzed the existing routing randomization methods and found that their security and usability need to be further improved. According to the characteristics of eavesdropping attacks, which are “latent and transferable”, a routing randomization defense method based on deep reinforcement learning is proposed. The proposed method realizes routing randomization on packet-level granularity using programmable switches. To improve the security and quality of service of legitimate services in networks, we use the deep deterministic policy gradient to generate random routing schemes with support from powerful network state awareness. In-band network telemetry provides real-time, accurate, and comprehensive network state awareness for the proposed method. Various experiments show that compared with other typical routing randomization defense methods, the proposed method has obvious advantages in security and usability against eavesdropping attacks.
基金supported by the National Natural Science Foundation of China(Grant number:81973256/H3008)Guangdong Basic and Applied Basic Research Foundation(Grant number:2021A1515010475)the Fundamental Research Funds for the Central Universities(22qntd4505).
文摘Photodynamic therapy(PDT)-mediated oxidation treatment is extremely attractive for skin melanoma ablation,but the strong hydrophobicity and poor tumor selectivity of photosensitizers,as well as the oxygen-consuming properties of PDT,leading to unsatisfactory therapeutic outcomes.Herein,a tumor acidic microenvironment activatable dissolving microneedle(DHA@HPFe-MN)was developed to realize controlled drug release and excellent chemo-photodynamic therapy of melanoma via oxidative stress amplification.The versatile DHA@HPFe-MN was fabricated by crosslinking a self-synthesized protoporphyrin(PpIX)-ADH-hyaluronic acid(HA)conjugate HA-ADH-PpIX with“iron reservoir”PA-Fe 3+complex in the needle tip via acylhydrazone bond formation,and dihydroartemisinin(DHA)was concurrently loaded in the hydrogel network.HA-ADH-PpIX with improved water solubility averted undesired aggregation of PpIX to ensure enhanced PDT effect.DHA@HPFe-MN with sharp needle tip,efficient drug loading and excellent mechanical strength could efficiently inserted into skin and reach the melanoma sites,where the acidic pH triggered the degradation of microneedles,enabling Fe-activated and DHA-mediated oxidation treatment,as evidenced by abundant reactive oxygen species(ROS)generation.Moreover,under light irradiation,a combined chemo-photodynamic therapeutic effect was achieved with amplified ROS generation.Importantly,the Fe-catalyzed ROS production of DHA was oxygen-independent,which work in synergy with the oxygen-dependent PDT to effectively destroy tumor cells.This versatile microneedles with excellent biosafety and biodegradability can be customized as a promising localized drug delivery system for combined chemo-photodynamic therapy of melanoma.
文摘Purpose:To report an unusual case of idiopathic orbital inflammation associated with panuveitis. Case report:We report a case of a 47-year-old female with a history of uveitis who presented with abrupt and painful prop tosis with complete vision loss unresponsive to antibiotic therapy.B-scan ultrasonography and magnetic resonance imaging both showed retinal detachment and an orbital space-occupying mass. The patient underwent orbitotomy and the diagnosis of idiopathic orbital inflammation was confirmed by histopathology. Anterior uveitis is rarely seen in idiopathic orbital inflammation in adults. We report for the first time an unusual case of idiopathic orbital inflammation associated with panuveitis. Conclusion:Inflammation involving both the eye and the orbit is rarely seen in adults. Idiopathic orbital inflammation and panuveitis may share a similar mechanism in this case. (Eye Science 2013; 28:40-43)
文摘AIM To assess the effects of probiotic Medilac-S~ as adjunctive therapy for the induction of remission of ulcerative colitis(UC) in a Chinese population through a systematic review and meta-analysis. METHODS A systematic literature search was conducted to find randomized, controlled trials in a Chinese population with at least two study arms-a control arm which receives a conventional, oral aminosalicylate drug, and a treatment arm, which administers the same conventional drug in conjunction with the probiotic Medilac-S~ per os. Both English and Chinese databases were searched, including Pub Med, EMBASE, Google Scholar, Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Search, and study data was extracted onto standardized abstraction sheets. Meta-analyses were conducted for primary and secondary outcomes of interest using a fixed or random effects model. The primary outcome was the induction of clinical remission and the secondary outcomes included changes in Sutherland index, endoscopic and histological scores, proportion of reported clinical symptoms and adverse events(AEs). For outcomes with sufficient data, the type of conventional drug therapy was also assessed to determine if the effects of combination therapy with Medilac-S~ was influenced by drug type. All tests were conducted using a type Ⅰ error rate of 0.05 and all confidence intervals(CI) were based on a 95% confidence level. Review protocol was uploaded to PROSPERO(CRD42018085658 upon completion).RESULTS Fifty-three clinical trials with a total of 3984 participants were identified and included in the review. Medilac-S~ adjunctive therapy significantly improved induction of clinical remission(RR = 1.21; 95%CI: 1.18-1.24; P < 0.0001) with the estimated likelihood of effective treatment, on average, 21% higher for those consuming the probiotic. Sutherland index scores showed the control mean was on average 3.10(CI: 2.41-3.78; P = 0.0428) units greater than the treatment mean, thereby demonstrating significant improvement in participants taking the probiotic. Similarly, a significant difference was seen between the overall reduction of endoscopic and histological scores of control and treatment arm participants, with score decreases in the control groups 0.71(CI: 0.3537-1.0742) and 1.1(CI: 0.9189-1.2300) units smaller than treatment group score decreases. The proportion of participants reporting clinical symptoms,(abdominal pain, tenesmus, blood and mucous in stool, and diarrhea) was significantly reduced after combination therapy with Medilac-S~(P < 0.0001) and estimated to be on average 44%(RR = 0.44, CI: 0.32-0.59), 53%(RR = 0.53, CI: 0.38-74), 40%(RR = 0.40, CI: 0.28-0.58) and 47%(RR = 0.47 CI: 0.36-0.42) respectively, of the proportion of individuals reporting the aforementioned symptoms after conventional therapy alone. The risk of AEs was also significantly reduced with adjunctive Medilac-S~ therapy. The proportion of individuals in the treatment groups reporting AEs was an estimated 72% of the proportion of individuals in the control groups reporting AEs(RR = 0.72, CI: 0.55-0.94, P = 0.0175). Upon comparing effect means for different drug types in conjunction with Medilac-S~, evidence of significant variability(P < 0.0001) was observed, and sulfasalazine was found to be the most effective drug in both primary and secondary outcomes. CONCLUSION Evidence suggests Medilac-S~ adjunctive therapy should be considered standard care for UC in a Chinese population because it aids in the induction of clinical remission, improves symptoms of the gastrointestinal tract and reduces risk of AEs.
基金Agency for Science,Technology and Research for its funding(U21-M1-019AR).
文摘The solid-state electrolyte in a solid-state battery acts as an electrons'barrier and an ions'bridge between the two electrodes.As solid-state electrolyte does not store the mobile ions,it is necessary to achieve a thin solid-state electrolyte to reduce the internal resistance and enhance the energy density.In this work,a thin NASICON solid-state electrolyte,with a stoichiometry of Na_(3)Zr_(2)Si_(2)PO_(12),is fabricated by the tape-casting method and its thickness can be easily controlled by the gap between substrate and scraper.The areal-specific resistance and the flexural strength increase with the electrolyte thickness.A solid-state sodium metal battery with 86 pm thick Na_(3)Zr_(2)Si_(2)PO_(12)exhibits a reversible specific capacity of 73-78 mAh g^(-1)with a redox potential of 3.4 V at 0.2 C.This work presents the importance of electrolyte thickness to reduce internal resistance and achieve a high energy density for sodium batteries.
基金financially supported by the National Natural Science Foundation of China(Grant number:81973256/H3008,82173748/H3408)。
文摘Posterior capsular opacification(PCO)is the leading cause of vision loss after cataract,mainly caused by the adhesion,proliferation and trans-differentiation of post-operative residual lens epithelial cells(LECs).Effective PCO prevention remains a huge challenge to ophthalmologists and researches for decades.Herein,we developed a“NIR-triggered ROS storage”intraocular implant(CTR-Py-Pp IX)based on capsular tension ring(CTR),which is concurrently linked with photosensitizer protophorphyrin IX(Pp IX)and energy storage2-pyridone derivative(Py),to guarantee instantaneous and sustainable ROS generation for LECs killing,aiming to achieve more efficient and safer photodynamic therapy(PDT)to effectively prevent PCO.The silylated Pp IX-Si and Py-Si were covalently conjugated to the plasma activated CTR surface to obtain CTR-Py-Pp IX.Results demonstrated that CTR-Py-Pp IX had dual functions of PDT and battery,in which Pp IX could generate ROS extracellularly under irradiation,with one part directly inhibiting LECs by lipid peroxidation(LPO)induction of cell membranes.Meanwhile,the excess ROS stored in Py could be continuously released to amplify LPO levels after the irradiation was removed.Ultimately,the proliferation of LECs in capsular bag was completely inhibited under mild irradiation conditions,achieving a sustainable and controlled PDT effect for effective PCO prevention with good biocompatibility.This NIR-triggered ROS storage intraocular implant would provide a more efficient and safer approach for long-term PCO prevention.
基金supported by the National Natural Science Foundation of China(32070579 and 32370664 to Z.Y.,31871449 and 32170813 to J.C.)the Natural Science Foundation of Henan(222300420067 to Z.Y.)+3 种基金State Key Laboratory of Genetic Resources and Evolution Grant(GREKF20-13 to Z.Y)Innovation and Entrepreneurship Training Program(2022cxcy568,2022cxcy717 and 2023cxcy475 to Z.Y.)the 1.3·5 project for disciplines of excellence of West China Hospital,Sichuan University(ZYGD23026 and 2024HXFH035)Science and Technologyy Department of Sichuan province(2024NSFSC0651).
文摘The evolution of light-skin pigmentation among Eurasians is considered as an adaptation to the high-latitude environments.East Asians are ideal populations for studying skin color evolution because of the complex environment of East Asia.Here,we report a strong selection signal for the pigmentation gene phenylalanine hydroxylase(PAH)in light-skinned Han Chinese individuals.The intron mutation rs10778203 in PAH is enriched in East Asians and is significantly associated with skin color of the back of the hand in Han Chinese males(P<0.05).In vitro luciferase and transcription factor binding assays show that the ancestral allele of rs10778203 could bind to SMAD2 and has a significant enhancer activity for PAH.However,the derived T allele(the major allele in East Asians)of rs10778203 decreases the binding activity of transcription factors and enhancer activity.Meanwhile,the derived T allele of rs10778203 shows a weaker ultraviolet radiation response in A375 cells and zebrafish embryos.Furthermore,rs10778203 decreases melanin production in transgenic zebrafish embryos after ultraviolet B(UVB)treatment.Collectively,PAH is a potential pigmentation gene that regulates skin tanning ability.Natural selection has enriched the adaptive allele,resulting in weakened tanning ability in East Asians,suggesting a unique genetic mechanism for evolutionary skin lightening in East Asians.
基金supported by the National Natural Science Foundation of China(Grant No.22005048)the Natural Science Foundation of Jiangsu Province(Grant No.BK20200399)+1 种基金the Fundamental Research Funds for the Central Universities(Grant No.2242023K40008)the State Key Laboratory of Clean Energy Utilization of Zhejiang University(Open Fund Project No.ZJUCEU2022003).
文摘Polyimide(PI)has emerged as a promising organic photocatalyst owing to its distinct advantages of high visible-light response,facile synthesis,molecularly tunable donor-acceptor structure,and excellent physicochemical stability.However,the synthesis of high-quality PI photoelectrode remains a challenge,and photoelectrochemical(PEC)water splitting for PI has been less studied.Herein,the synthesis of uniform PI photoelectrode films via a simple spin-coating method was reported,and their PEC properties were investigated using melamine as donor and various anhydrides as acceptors.The influence of the conjugate size of aromatic unit(phenyl,biphenyl,naphthalene,perylene)of electron acceptor on PEC performance were studied,where naphthalene-based PI photoelectrode exhibited the highest photocurrent response.This is resulted from the unification of widerange light absorption,efficient charge separation and transport,and strong photooxidation capacity.This paper expands the material library of polymer films for PEC applications and contributes to the rational design of efficient polymer photoelectrodes.
基金supported by National Natural Science Foundation Grants(T2394480,T2394482,12034006,32200135,32200138,32371286)National Key Research and Development Program(2018YFA0900801,2023YFC2306603)+4 种基金Ministry of Science and Technology of China(CPL-1233 and SRPG22-003)Chinese Academy of Sciences(YSBR-010)supported by National Science Fund for Distinguished Young Scholar(No.32325004)the NSFC Innovative Research Group(No.81921005)supported by Jiangsu Province Science and Technology Achievement Transformation Special Project(BA2023012).
文摘In more than 200 years since Edward Jenner successfully developed the first vaccine for combating smallpox,vaccines have played pivotal roles in preventing outbreaks of several infectious diseases,and it could even be asserted that each one of us has benefited from them.The recent severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)outbreak has also demonstrated the importance of vaccines in interrupting the transmission of infectious diseases(Deng and Peng,2020).
基金supported by the Shandong Province Major Scientific and Technological Innovation Project(China)(No.2020CXGC010503)the Shandong Provincial Key Laboratory Platform Project(China)(No.2021ZDSYS11)the National Natural Science Foundation of China Major Project(No.81991525).
文摘Interleukin-6(IL-6)is a common pluripotent cytokine that is highly expressed in the tumor microenvironment.The IL-6/JAK/STAT3 signaling directly promotes tumor progression,severely hampering antitumor immunity.Macrophages,the richest innate immune cells within the tumor microenvironment,manipulate tumor progression via phenotypic plasticity.
基金supported by grants from the Guangdong Basic and Applied Basic Research Foundation(2023A1515011250).
文摘Dominant optic atrophy(DOA)is an inherited optic neuropathy and more than 75%of DOA patients harbor pathogenic mutations in OPA1.We reported a 39-year-old female harboring c.2119G>T mutation of OPA1 and manifested progressive visual impairment after hydroxychloroquine(HCQ)therapy.The patient’s visual impairment remained stable for 10 years until she began to take HCQ 13 months ago.She complained about progressively decreased vision in both eyes.Bilateral pale temporal optic disc was similar with that of 11 years ago.Optical coherence tomography showed bilateral moderate retinal nerve fiber layer thinning other than the nasal quadrant and general thinning of the inner retina in the macular.Microcystic macular edema was noted in nasal macular in both eyes.Visual field testing showed paracentral scotoma and microperimetry showed decrease sensitivity in the macular in both eyes.After the patient stopped taking HCQ,her functional tests including visual acuity,field testing and microperimetry testing was stable compared with those of 2 years ago.However,progressive inner macular and RNFL thinning was shown by OCT.OPA1 c.2119 G>T found in this patient was a mutation that had been rarely reported in previous studies.The patient has been followed up for over 10 years and her visual acuity stayed stable for decades long until she took HCQ for 13 months.Her vision decline terminated after she stopped taking HCQ.Although HCQ toxicity is highly related to the duration and daily dose,HCQ may aggravate visual impairment in certain individuals harboring OPA1 mutation.Patients with DOA should avoid using neurotoxic HCQ and other medications that may interfere mitochondrial metabolism.
基金This study was financially supported by the National Natural Science Foundation of China(81772713,81472411,81401899,81372752)Taishan Scholar Program of Shandong Province(tsqn20161077)+4 种基金Key Research and Development Program of Shandong Province(2018GSF118197)China Postdoctoral Science Foundation(2017M622144)Qingdao Postdoctoral Application Research Project.Prof.Zhang acknowledged the support from Academy of Finland(Grant no.328933)Sigrid Juselius Foundation(Grant no.28002247K1)We thank Dr.Chang Liu fromÅbo Akademi University for giving some advice to analyze the TGA data,and Ms.Qian Wen from Biomedical Center of Qingdao University for her guidance and support of in vivo fluorescence imaging.
文摘Bladder cancer is one of the concerning malignancies worldwide,which is lacking effective targeted therapy.Gene therapy is a potential approach for bladder cancer treatment.While,a safe and effective targeted gene delivery system is urgently needed for prompting the bladder cancer treatment in vivo.In this study,we confirmed that the bladder cancer had CD44 overexpression and small interfering RNAs(siRNA)with high interfere to Bcl2 oncogene were designed and screened.Then hyaluronic acid dialdehyde(HAD)was prepared in an ethanol-water mixture and covalently conjugated to the chitosan nanoparticles(CS-HAD NPs)to achieve CD44 targeted siRNA delivery.The in vitro and in vivo evaluations indicated that the siRNA-loaded CS-HAD NPs(siRNA@CS-HAD NPs)were approximately 100 nm in size,with improved stability,high siRNA encapsulation efficiency and low cytotoxicity.CS-HAD NPs could target to CD44 receptor and deliver the therapeutic siRNA into T24 bladder cancer cells through a ligand-receptor-mediated targeting mechanism and had a specific accumulation capacity in vivo to interfere the targeted oncogene Bcl2 in bladder cancer.Overall,a CD44 targeted gene delivery system based on natural macromolecules was developed for effective bladder cancer treatment,which could be more conducive to clinical application due to its simple preparation and high biological safety.
基金supported by CAMS Innovation Fund for Medical Sciences(No. 2016-12M-1-009)National Scientific and Technological Major Project for New Drugs(No.2017ZX09101003-002-004)
文摘A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry(UPLC–MS/MS) method was developed and fully validated for determination of arformoterol in rat plasma, lung and trachea tissues. The chromatographic separation was performed on an Agilent XDB C8 column with gradient elution by using acetonitrile and 0.1% formic acid water. The method presented high sensitivity(LLOQ of 1.83 pg/mL for plasma and 3.90 pg/mL for lung and trachea tissue homogenates) and great linearity over the range of 1.83–458 pg/mL for plasma, 13.9–1560 pg/mL for lung and trachea tissue homogenates. No carry over effect and matrix effect were observed. The intra-and inter-day precision/accuracy were within ±15% at three quality control concentration levels. This robust method was successfully applied to the pharmacokinetic, lung and trachea tissue distribution study after inhalation administration of arformoterol tartrate inhalation solution(50 m g/kg). The in vivo information indicate that arformoterol can be rapidly absorbed into blood through respiratory systems, lung and trachea tissue maintain a certain amount of arformoterol in 1 h after dosing.