Deep and ultra-deep reservoirs have dense matrix and high fracture pressure, which leads to high pressure and difficulty in fracturing construction. Conventional aggravated fracturing fluids have the problems of low a...Deep and ultra-deep reservoirs have dense matrix and high fracture pressure, which leads to high pressure and difficulty in fracturing construction. Conventional aggravated fracturing fluids have the problems of low aggravation efficiency, high friction resistance, etc., and the reduction of construction pressure cannot reach the theoretical effect. In view of the above problems, this paper adopts the weighting agent HD160 and the drag reducing agent JHFR-2 to form a new type of weighted slippery water fracturing fluid system. And the weighting performance, drag reduction performance, corrosion performance, anti-expansion performance and reservoir damage of this system were studied. The results show that the density of the system is adjustable within 1.1 - 1.6 g·cm−3, and the drag reduction rate can be up to 68% at 1.5 g·cm−3, with low corrosion rate, surface tension less than 28 mN·m−1, anti-expansion rate as high as 94.5%, and the damage rate of the reservoir permeability is less than 10%, which is of good application prospect.展开更多
Natural slopes usually display complicated exposed rock surfaces that are characterized by complex and substantial terrain undulation and ubiquitous undesirable phenomena such as vegetation cover and rockfalls.This st...Natural slopes usually display complicated exposed rock surfaces that are characterized by complex and substantial terrain undulation and ubiquitous undesirable phenomena such as vegetation cover and rockfalls.This study presents a systematic outcrop research of fracture pattern variations in a complicated rock slope,and the qualitative and quantitative study of the complex phenomena impact on threedimensional(3D)discrete fracture network(DFN)modeling.As the studies of the outcrop fracture pattern have been so far focused on local variations,thus,we put forward a statistical analysis of global variations.The entire outcrop is partitioned into several subzones,and the subzone-scale variability of fracture geometric properties is analyzed(including the orientation,the density,and the trace length).The results reveal significant variations in fracture characteristics(such as the concentrative degree,the average orientation,the density,and the trace length)among different subzones.Moreover,the density of fracture sets,which is approximately parallel to the slope surface,exhibits a notably higher value compared to other fracture sets across all subzones.To improve the accuracy of the DFN modeling,the effects of three common phenomena resulting from vegetation and rockfalls are qualitatively analyzed and the corresponding quantitative data processing solutions are proposed.Subsequently,the 3D fracture geometric parameters are determined for different areas of the high-steep rock slope in terms of the subzone dimensions.The results show significant variations in the same set of 3D fracture parameters across different regions with density differing by up to tenfold and mean trace length exhibiting differences of 3e4 times.The study results present precise geological structural information,improve modeling accuracy,and provide practical solutions for addressing complex outcrop issues.展开更多
PTEN-induced putative kinase 1(PINK1),a mitochondrial kinase that phosphorylates Parkin and other proteins,plays a crucial role in mitophagy and protection against neurodegeneration.Mutations in PINK1 and Parkin can l...PTEN-induced putative kinase 1(PINK1),a mitochondrial kinase that phosphorylates Parkin and other proteins,plays a crucial role in mitophagy and protection against neurodegeneration.Mutations in PINK1 and Parkin can lead to loss of function and early onset Parkinson's disease.However,there is a lack of strong in vivo evidence in rodent models to support the theory that loss of PINK1 affects mitophagy and induces neurodegeneration.Additionally,PINK1 knockout pigs(Sus scrofa)do not appear to exhibit neurodegeneration.In our recent work involving non-human primates,we found that PINK1 is selectively expressed in primate brains,while absent in rodent brains.To extend this to other species,we used multiple antibodies to examine the expression of PINK1 in pig tissues.In contrast to tissues from cynomolgus monkeys(Macaca fascicularis),our data did not convincingly demonstrate detectable PINK1expression in pig tissues.Knockdown of PINK1 in cultured pig cells did not result in altered Parkin and BAD phosphorylation,as observed in cultured monkey cells.A comparison of monkey and pig striatum revealed more PINK1-phosphorylated substrates in the monkey brain.Consistently,PINK1 knockout in pigs did not lead to obvious changes in the phosphorylation of Parkin and BAD.These findings provide new evidence that PINK1expression is specific to primates,underscoring the importance of non-human primates in investigating PINK1function and pathology related to PINK1 deficiency.展开更多
Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and e...Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.展开更多
AIM:To report a one-year clinical outcomes of low-dose laser cycloplasty(LCP)among malignant glaucoma patients.METHODS:In this prospective,multicenter,noncomparative clinical study,participants with malignant glaucoma...AIM:To report a one-year clinical outcomes of low-dose laser cycloplasty(LCP)among malignant glaucoma patients.METHODS:In this prospective,multicenter,noncomparative clinical study,participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China.Patients were followed up at 1wk,1,3,6,and 12mo.Intraocular pressure(IOP),number of glaucoma medications,anterior chamber depth(ACD),and complications were recorded.Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy.Recurrence was defined by the presence of a shallow orflat anterior chamber after initial recovery from treatment.RESULTS:A total of 34 eyes received LCP.Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg(P<0.001)with 2.9±1.6 medications(P=0.046)at 1d,and 17.4±6.7 mm Hg(P<0.001)with 1.3±1.7 medications(P<0.001)at 12mo.The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo,respectively.A total of 32(94.1%)eyes achieved initial anatomical success.During follow-up,2(5.9%)eyes failed and 8(23.5%)eyes relapsed,yielding a 12-month anatomical success rate of 64.3%.Complications including anterior synechia(8.82%),choroidal/ciliary detachment(5.88%)and hypopyon(2.94%)were observed within 1wk.CONCLUSION:LCP is simple,safe,and effective in reforming the anterior chamber in malignant glaucoma.展开更多
In this paper,we consider mobile edge computing(MEC)networks against proactive eavesdropping.To maximize the transmission rate,IRS assisted UAV communications are applied.We take the joint design of the trajectory of ...In this paper,we consider mobile edge computing(MEC)networks against proactive eavesdropping.To maximize the transmission rate,IRS assisted UAV communications are applied.We take the joint design of the trajectory of UAV,the transmitting beamforming of users,and the phase shift matrix of IRS.The original problem is strong non-convex and difficult to solve.We first propose two basic modes of the proactive eavesdropper,and obtain the closed-form solution for the boundary conditions of the two modes.Then we transform the original problem into an equivalent one and propose an alternating optimization(AO)based method to obtain a local optimal solution.The convergence of the algorithm is illustrated by numerical results.Further,we propose a zero forcing(ZF)based method as sub-optimal solution,and the simulation section shows that the proposed two schemes could obtain better performance compared with traditional schemes.展开更多
BACKGROUND Melioidosis,an infectious disease caused by Burkholderia pseudomallei(B.pseudomallei),occurs endemically in Southeast Asia and Northern Australia and is a serious opportunistic infection associated with a h...BACKGROUND Melioidosis,an infectious disease caused by Burkholderia pseudomallei(B.pseudomallei),occurs endemically in Southeast Asia and Northern Australia and is a serious opportunistic infection associated with a high mortality rate.CASE SUMMARY A 58-year-old woman presented with scattered erythema on the skin of her limbs,followed by fever and seizures.B.pseudomallei was isolated successively from the patient’s urine,blood,and pus.Magnetic resonance imaging showed abscess formation involving the right forehead and the right frontal region.Subsequently,abscess resection and drainage were performed.The patient showed no signs of relapse after 4 months of follow-up visits post-treatment.CONCLUSION We present here a unique case of multi-systemic melioidosis that occurs in nonendemic regions in a patient who had no recent travel history.Hence,it is critical to enhance awareness of melioidosis in non-endemic regions.展开更多
Understanding the relationship between forest management and water use efficiency(WUE)is important for evaluating forest adaptability to climate change.However,the effects of thinning and understory removal on WUE and...Understanding the relationship between forest management and water use efficiency(WUE)is important for evaluating forest adaptability to climate change.However,the effects of thinning and understory removal on WUE and its key controlling processes are not well understood,which limits our comprehension of the physiological mechanisms of various management practices.In this study,four forest management measures(no thinning:NT;understory removal:UR;light thinning:LT;and heavy thinning:HT)were carried out in Pinus massoniana plantations in a subtropical region of China.Photosynthetic capacity and needle stable carbon isotope composition(δ^(13)C)were measured to assess instantaneous water use efficiency(WUE_(inst))and long-term water use efficiency(WUE_(i)).Multiple regression models and structural equation modelling(SEM)identified the effects of soil properties and physiological performances on WUE_(inst)and WUE_(i).The results show that WUE_(inst)values among the four treatments were insignificant.However,compared with the NT stand(35.8μmol·mol^(-1)),WUE_(i)values significantly increased to 41.7μmol·mol^(-1)in the UR,50.1μmol·mol^(-1)in the LT and 46.6μmol·mol^(-1)in HT treatments,largely explained by photosynthetic capacity and soil water content.Understory removal did not change physiological performance(needle water potential and photosynthetic capacity).Thinning increased the net photosynthetic rate(A_n)but not stomatal conductance(g_s)or predawn needle water potential(ψ_(pd)),implying that the improvement in water use efficiency for thinned stands was largely driven by radiation interception than by soil water availability.In general,thinning may be an appropriate management measure to promote P.massoniana WUE to cope with seasonal droughts under future extreme climates.展开更多
Gabapentinoid drugs(pregabalin and gabapentin) have been successfully used in the treatment of neuro pathic pain and in focal seizure prevention.Recent research has demonstrated their potent activities in modulating n...Gabapentinoid drugs(pregabalin and gabapentin) have been successfully used in the treatment of neuro pathic pain and in focal seizure prevention.Recent research has demonstrated their potent activities in modulating neurotransmitter release in neuronal tissue,oxidative stress,and inflammation,which matches the mechanism of action via voltage-gated calcium channels.In this review,we briefly elaborate on the medicinal history and ligand-binding sites of gabapentinoids.We systematically summarize the preclinical and clinical research on gabapentinoids in stroke,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,seizures after stro ke,cortical spreading depolarization after stroke,pain after stroke,and nerve regeneration after stro ke.This review also discusses the potential to rgets of gabapentinoids in stroke;however,the existing results are still unce rtain regarding the effect of gabapentinoids on stroke and related diseases.Further preclinical and clinical trials are needed to test the therapeutic potential of gabapentinoids in stroke.Therefore,gabapentinoids have both opportunities and challenges in the treatment of stroke.展开更多
This paper proposes luteolin(LUT)as a novel depressant for the flotation-based separation of scheelite and calcite in a sodium oleate(NaOL)system.The suitability of LUT as a calcite depressant is confirmed through mic...This paper proposes luteolin(LUT)as a novel depressant for the flotation-based separation of scheelite and calcite in a sodium oleate(NaOL)system.The suitability of LUT as a calcite depressant is confirmed through micro-flotation testing.At pH=9,with LUT concentration of 50 mg·L^(-1) and NaOL concentration of 50 mg·L^(-1),scheelite recovery reaches 80.3%.Calcite,on the other hand,exhibits a recovery rate of 17.6%,indicating a significant difference in floatability between the two minerals.Subsequently,the surface modifica-tions of scheelite and calcite following LUT treatment are characterized using adsorption capacity testing,Zeta potential analysis,Fourier transform infrared spectroscopy(FT-IR),X-ray photoelectron spectroscopy(XPS),and atomic force microscopy(AFM).The study in-vestigates the selective depressant mechanism of LUT on calcite.Adsorption capacity testing and Zeta potential analysis demonstrate sub-stantial absorption of LUT on the surface of calcite,impeding the further adsorption of sodium oleate,while its impact on scheelite is min-imal.FT-IR and XPS analyses reveal the selective adsorption of LUT onto the surface of calcite,forming strong chemisorption bonds between the hydroxyl group and calcium ions present.AFM directly illustrates the distinct adsorption densities of LUT on the two miner-al types.Consequently,LUT can effectively serve as a depressant for calcite,enabling the successful separation of scheelite and calcite.展开更多
Thermal stress causes the overproduction and toxic accumulation of reactive oxygen species(ROS),which seems to be correlated with coral bleaching and,ultimately,death.The reduction of ROS concentration within the cora...Thermal stress causes the overproduction and toxic accumulation of reactive oxygen species(ROS),which seems to be correlated with coral bleaching and,ultimately,death.The reduction of ROS concentration within the coral holobiont could minimize the effects of thermal stress and support efforts to reduce coral decline globally.In the current study,we explored the physiological responses of Pocillopora damicornis to ROS-scavenging bacteria inoculation as well as the microbiome restructuring that correlates with P.damicornis’s resilience to thermal stress after probiotic inoculation.Inoculation of corals with ROS-scavenging bacteria enhanced coral health and reduced ROS concentration.Furthermore,the enhanced coral thermal resistance promoted by ROS-scavenging bacteria was also correlated with an overall coral microbiome restructuring.In addition,the complex network relationships between bacteria and Symbiodiniaceae in corals after ROS-scavenging bacteria inoculation contributed to corals’resilience to high temperatures.Besides,coral heat tolerance bacterial biomarkers,such as Myxococcota,were enriched in corals with added ROS-scavenging bacteria.Collectively,our findings validate the selected ROS-scavenging bacteria as coral probiotics that could help corals resist thermal stress on a short timescale.Additionally,our data contribute to our understanding of the potential interactions between different members of the coral holobiont and the use of probiotics as tools to aid coral restoration efforts.展开更多
The matrix thermal properties have an important impact on laser-induced plasma,as the thermal effect dominates the interaction between ns-pulsed laser and matter,especially in metals.We used a series of pure metals an...The matrix thermal properties have an important impact on laser-induced plasma,as the thermal effect dominates the interaction between ns-pulsed laser and matter,especially in metals.We used a series of pure metals and aluminum alloys to measure plasma temperature and electron density through laser-induced breakdown spectroscopy,in order to investigate the effect of matrix thermal properties on laser-induced plasma.In pure metals,a significant negative linear correlation was observed between the matrix thermal storage coefficient and plasma temperature,while a weak correlation was observed with electron density.The results indicate that metals with low thermal conductivity or specific heat capacity require less laser energy for thermal diffusion or melting and evaporation,resulting in higher ablation rates and higher plasma temperatures.However,considering ionization energy,thermal effects may be a secondary factor affecting electron density.The experiment of aluminum alloy further confirms the influence of thermal conductivity on plasma temperature and its mechanism explanation.展开更多
Industrial CO_(2)electroreduction has received tremendous attentions for resolution of the current energy and environmental crisis,but its performance is greatly limited by mass transport at high current density.In th...Industrial CO_(2)electroreduction has received tremendous attentions for resolution of the current energy and environmental crisis,but its performance is greatly limited by mass transport at high current density.In this work,an ion‐polymer‐modified gas‐diffusion electrode is used to tackle this proton limit.It is found that gas diffusion electrode‐Nafion shows an impressive performance of 75.2%Faradaic efficiency in multicarbon products at an industrial current density of 1.16 A/cm^(2).Significantly,in‐depth electrochemical characterizations combined with in situ Raman have been used to determine the full workflow of protons,and it is found that HCO_(3)^(−)acts as a proton pool near the reaction environment,and HCO_(3)^(−)and H_(3)O^(+)are local proton donors that interact with the proton shuttle−SO_(3)^(−)from Nafion.With rich proton hopping sites that decrease the activation energy,a“Grotthuss”mechanism for proton transport in the above system has been identified rather than the“Vehicle”mechanism with a higher energy barrier.Therefore,this work could be very useful in terms of the achievement of industrial CO_(2)reduction fundamentally and practically.展开更多
Highly thermally conductive graphitic film(GF)materials have become a competitive solution for the thermal management of high-power electronic devices.However,their catastrophic structural failure under extreme altern...Highly thermally conductive graphitic film(GF)materials have become a competitive solution for the thermal management of high-power electronic devices.However,their catastrophic structural failure under extreme alternating thermal/cold shock poses a significant challenge to reliability and safety.Here,we present the first investigation into the structural failure mechanism of GF during cyclic liquid nitrogen shocks(LNS),which reveals a bubbling process characterized by“permeation-diffusion-deformation”phenomenon.To overcome this long-standing structural weakness,a novel metal-nanoarmor strategy is proposed to construct a Cu-modified graphitic film(GF@Cu)with seamless heterointerface.This well-designed interface ensures superior structural stability for GF@Cu after hundreds of LNS cycles from 77 to 300 K.Moreover,GF@Cu maintains high thermal conductivity up to 1088 W m^(−1)K^(−1)with degradation of less than 5%even after 150 LNS cycles,superior to that of pure GF(50%degradation).Our work not only offers an opportunity to improve the robustness of graphitic films by the rational structural design but also facilitates the applications of thermally conductive carbon-based materials for future extreme thermal management in complex aerospace electronics.展开更多
The Mean First-Passage Time (MFPT) and Stochastic Resonance (SR) of a stochastic tumor-immune model withnoise perturbation are discussed in this paper. Firstly, considering environmental perturbation, Gaussian whiteno...The Mean First-Passage Time (MFPT) and Stochastic Resonance (SR) of a stochastic tumor-immune model withnoise perturbation are discussed in this paper. Firstly, considering environmental perturbation, Gaussian whitenoise and Gaussian colored noise are introduced into a tumor growth model under immune surveillance. Asfollows, the long-time evolution of the tumor characterized by the Stationary Probability Density (SPD) and MFPTis obtained in theory on the basis of the Approximated Fokker-Planck Equation (AFPE). Herein the recurrenceof the tumor from the extinction state to the tumor-present state is more concerned in this paper. A moreefficient algorithmof Back-Propagation Neural Network (BPNN) is utilized in order to testify the correction of thetheoretical SPDandMFPT.With the existence of aweak signal, the functional relationship between Signal-to-NoiseRatio (SNR), noise intensities and correlation time is also studied. Numerical results show that both multiplicativeGaussian colored noise and additive Gaussian white noise can promote the extinction of the tumors, and themultiplicative Gaussian colored noise can lead to the resonance-like peak on MFPT curves, while the increasingintensity of the additiveGaussian white noise results in theminimum of MFPT. In addition, the correlation timesare negatively correlated with MFPT. As for the SNR, we find the intensities of both the Gaussian white noise andthe Gaussian colored noise, as well as their correlation intensity can induce SR. Especially, SNR is monotonouslyincreased in the case ofGaussian white noisewith the change of the correlation time.At last, the optimal parametersin BPNN structure are analyzed for MFPT from three aspects: the penalty factors, the number of neural networklayers and the number of nodes in each layer.展开更多
Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs.Curren...Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs.Current knockout strategies are mainly aimed at the genes causing hyperacute immune rejection(HAR)that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure,in which process the MHCⅡmolecule plays critical roles.Methods:Thus,we generate a 4-gene(GGTA1,CMAH,β4GalNT2,and CIITA)knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously.Results:We successfully obtained 4KO piglets with deficiency in all alleles of genes,and at cellular and tissue levels.Additionally,the safety of our animals after gene editing was verified by using whole-genome sequencing and karyotyping.Piglets have survived for more than one year in the barrier,and also survived for more than 3 months in the conventional environment,suggesting that the piglets without MHCⅡcan be raised in the barrier and then gradually mated in the conventional environment.Conclusions:4KO piglets have lower immunogenicity,are safe in genomic level,and are easier to breed than the model with both MHCⅠandⅡdeletion.展开更多
文摘Deep and ultra-deep reservoirs have dense matrix and high fracture pressure, which leads to high pressure and difficulty in fracturing construction. Conventional aggravated fracturing fluids have the problems of low aggravation efficiency, high friction resistance, etc., and the reduction of construction pressure cannot reach the theoretical effect. In view of the above problems, this paper adopts the weighting agent HD160 and the drag reducing agent JHFR-2 to form a new type of weighted slippery water fracturing fluid system. And the weighting performance, drag reduction performance, corrosion performance, anti-expansion performance and reservoir damage of this system were studied. The results show that the density of the system is adjustable within 1.1 - 1.6 g·cm−3, and the drag reduction rate can be up to 68% at 1.5 g·cm−3, with low corrosion rate, surface tension less than 28 mN·m−1, anti-expansion rate as high as 94.5%, and the damage rate of the reservoir permeability is less than 10%, which is of good application prospect.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFC3080200)the National Natural Science Foundation of China(Grant No.42022053)the China Postdoctoral Science Foundation(Grant No.2023M731264).
文摘Natural slopes usually display complicated exposed rock surfaces that are characterized by complex and substantial terrain undulation and ubiquitous undesirable phenomena such as vegetation cover and rockfalls.This study presents a systematic outcrop research of fracture pattern variations in a complicated rock slope,and the qualitative and quantitative study of the complex phenomena impact on threedimensional(3D)discrete fracture network(DFN)modeling.As the studies of the outcrop fracture pattern have been so far focused on local variations,thus,we put forward a statistical analysis of global variations.The entire outcrop is partitioned into several subzones,and the subzone-scale variability of fracture geometric properties is analyzed(including the orientation,the density,and the trace length).The results reveal significant variations in fracture characteristics(such as the concentrative degree,the average orientation,the density,and the trace length)among different subzones.Moreover,the density of fracture sets,which is approximately parallel to the slope surface,exhibits a notably higher value compared to other fracture sets across all subzones.To improve the accuracy of the DFN modeling,the effects of three common phenomena resulting from vegetation and rockfalls are qualitatively analyzed and the corresponding quantitative data processing solutions are proposed.Subsequently,the 3D fracture geometric parameters are determined for different areas of the high-steep rock slope in terms of the subzone dimensions.The results show significant variations in the same set of 3D fracture parameters across different regions with density differing by up to tenfold and mean trace length exhibiting differences of 3e4 times.The study results present precise geological structural information,improve modeling accuracy,and provide practical solutions for addressing complex outcrop issues.
基金supported by the National Natural Science Foundation of China (32070534,32370567,82371874,81830032,31872779,82071421,81873736)Key Field Research and Development Program of Guangdong Province (2018B030337001)+3 种基金Guangzhou Key Research Program on Brain Science (202007030008)Department of Science and Technology of Guangdong Province (2021ZT09Y007,2020B121201006)Guangdong Basic and Applied Basic Research Foundation (2023B1515020031,2022A1515012301)Fundamental Research Funds for the Central Universities (Jinan University,21620358)。
文摘PTEN-induced putative kinase 1(PINK1),a mitochondrial kinase that phosphorylates Parkin and other proteins,plays a crucial role in mitophagy and protection against neurodegeneration.Mutations in PINK1 and Parkin can lead to loss of function and early onset Parkinson's disease.However,there is a lack of strong in vivo evidence in rodent models to support the theory that loss of PINK1 affects mitophagy and induces neurodegeneration.Additionally,PINK1 knockout pigs(Sus scrofa)do not appear to exhibit neurodegeneration.In our recent work involving non-human primates,we found that PINK1 is selectively expressed in primate brains,while absent in rodent brains.To extend this to other species,we used multiple antibodies to examine the expression of PINK1 in pig tissues.In contrast to tissues from cynomolgus monkeys(Macaca fascicularis),our data did not convincingly demonstrate detectable PINK1expression in pig tissues.Knockdown of PINK1 in cultured pig cells did not result in altered Parkin and BAD phosphorylation,as observed in cultured monkey cells.A comparison of monkey and pig striatum revealed more PINK1-phosphorylated substrates in the monkey brain.Consistently,PINK1 knockout in pigs did not lead to obvious changes in the phosphorylation of Parkin and BAD.These findings provide new evidence that PINK1expression is specific to primates,underscoring the importance of non-human primates in investigating PINK1function and pathology related to PINK1 deficiency.
基金supported by the National Key Research and Development Program of China (2021YFA0805902,2022YFF0710703)National Natural Science Foundation of China (32201257)+1 种基金Science and Technology Innovation Project of Xiongan New Area (2022XAGG0121)Young Elite Scientists Sponsorship Program by the China Association for Science and Technology (2019QNRC001)。
文摘Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.
基金Supported by the Program for Zhejiang Leading Talent of S&T Innovation(No.2021R52012)Development Projects of Zhejiang Province(No.2022C03112)Innovation Team Program of Wenzhou.
文摘AIM:To report a one-year clinical outcomes of low-dose laser cycloplasty(LCP)among malignant glaucoma patients.METHODS:In this prospective,multicenter,noncomparative clinical study,participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China.Patients were followed up at 1wk,1,3,6,and 12mo.Intraocular pressure(IOP),number of glaucoma medications,anterior chamber depth(ACD),and complications were recorded.Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy.Recurrence was defined by the presence of a shallow orflat anterior chamber after initial recovery from treatment.RESULTS:A total of 34 eyes received LCP.Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg(P<0.001)with 2.9±1.6 medications(P=0.046)at 1d,and 17.4±6.7 mm Hg(P<0.001)with 1.3±1.7 medications(P<0.001)at 12mo.The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo,respectively.A total of 32(94.1%)eyes achieved initial anatomical success.During follow-up,2(5.9%)eyes failed and 8(23.5%)eyes relapsed,yielding a 12-month anatomical success rate of 64.3%.Complications including anterior synechia(8.82%),choroidal/ciliary detachment(5.88%)and hypopyon(2.94%)were observed within 1wk.CONCLUSION:LCP is simple,safe,and effective in reforming the anterior chamber in malignant glaucoma.
基金This work was supported by the Key Scientific and Technological Project of Henan Province(Grant Number 222102210212)Doctoral Research Start Project of Henan Institute of Technology(Grant Number KQ2005)Key Research Projects of Colleges and Universities in Henan Province(Grant Number 23B510006).
文摘In this paper,we consider mobile edge computing(MEC)networks against proactive eavesdropping.To maximize the transmission rate,IRS assisted UAV communications are applied.We take the joint design of the trajectory of UAV,the transmitting beamforming of users,and the phase shift matrix of IRS.The original problem is strong non-convex and difficult to solve.We first propose two basic modes of the proactive eavesdropper,and obtain the closed-form solution for the boundary conditions of the two modes.Then we transform the original problem into an equivalent one and propose an alternating optimization(AO)based method to obtain a local optimal solution.The convergence of the algorithm is illustrated by numerical results.Further,we propose a zero forcing(ZF)based method as sub-optimal solution,and the simulation section shows that the proposed two schemes could obtain better performance compared with traditional schemes.
文摘BACKGROUND Melioidosis,an infectious disease caused by Burkholderia pseudomallei(B.pseudomallei),occurs endemically in Southeast Asia and Northern Australia and is a serious opportunistic infection associated with a high mortality rate.CASE SUMMARY A 58-year-old woman presented with scattered erythema on the skin of her limbs,followed by fever and seizures.B.pseudomallei was isolated successively from the patient’s urine,blood,and pus.Magnetic resonance imaging showed abscess formation involving the right forehead and the right frontal region.Subsequently,abscess resection and drainage were performed.The patient showed no signs of relapse after 4 months of follow-up visits post-treatment.CONCLUSION We present here a unique case of multi-systemic melioidosis that occurs in nonendemic regions in a patient who had no recent travel history.Hence,it is critical to enhance awareness of melioidosis in non-endemic regions.
基金supported by the National Key Research and Development Program of China(2016YFD0600201)the National Nonprofit Institute Research Grant of CAF(CAFYBB2017ZB003)+1 种基金the National Natural Science Foundation of China(3187071631670720)。
文摘Understanding the relationship between forest management and water use efficiency(WUE)is important for evaluating forest adaptability to climate change.However,the effects of thinning and understory removal on WUE and its key controlling processes are not well understood,which limits our comprehension of the physiological mechanisms of various management practices.In this study,four forest management measures(no thinning:NT;understory removal:UR;light thinning:LT;and heavy thinning:HT)were carried out in Pinus massoniana plantations in a subtropical region of China.Photosynthetic capacity and needle stable carbon isotope composition(δ^(13)C)were measured to assess instantaneous water use efficiency(WUE_(inst))and long-term water use efficiency(WUE_(i)).Multiple regression models and structural equation modelling(SEM)identified the effects of soil properties and physiological performances on WUE_(inst)and WUE_(i).The results show that WUE_(inst)values among the four treatments were insignificant.However,compared with the NT stand(35.8μmol·mol^(-1)),WUE_(i)values significantly increased to 41.7μmol·mol^(-1)in the UR,50.1μmol·mol^(-1)in the LT and 46.6μmol·mol^(-1)in HT treatments,largely explained by photosynthetic capacity and soil water content.Understory removal did not change physiological performance(needle water potential and photosynthetic capacity).Thinning increased the net photosynthetic rate(A_n)but not stomatal conductance(g_s)or predawn needle water potential(ψ_(pd)),implying that the improvement in water use efficiency for thinned stands was largely driven by radiation interception than by soil water availability.In general,thinning may be an appropriate management measure to promote P.massoniana WUE to cope with seasonal droughts under future extreme climates.
基金supported by the National Key R&D Program of China,No.2020YFC2008302the National Natural Science Foundation of China,No.81673631the Science and Technology Program of Sichuan Province,No.2020YFH0059 (all to YL)。
文摘Gabapentinoid drugs(pregabalin and gabapentin) have been successfully used in the treatment of neuro pathic pain and in focal seizure prevention.Recent research has demonstrated their potent activities in modulating neurotransmitter release in neuronal tissue,oxidative stress,and inflammation,which matches the mechanism of action via voltage-gated calcium channels.In this review,we briefly elaborate on the medicinal history and ligand-binding sites of gabapentinoids.We systematically summarize the preclinical and clinical research on gabapentinoids in stroke,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,seizures after stro ke,cortical spreading depolarization after stroke,pain after stroke,and nerve regeneration after stro ke.This review also discusses the potential to rgets of gabapentinoids in stroke;however,the existing results are still unce rtain regarding the effect of gabapentinoids on stroke and related diseases.Further preclinical and clinical trials are needed to test the therapeutic potential of gabapentinoids in stroke.Therefore,gabapentinoids have both opportunities and challenges in the treatment of stroke.
基金supported by the National Natural Science Foundation of China (No.52164022).
文摘This paper proposes luteolin(LUT)as a novel depressant for the flotation-based separation of scheelite and calcite in a sodium oleate(NaOL)system.The suitability of LUT as a calcite depressant is confirmed through micro-flotation testing.At pH=9,with LUT concentration of 50 mg·L^(-1) and NaOL concentration of 50 mg·L^(-1),scheelite recovery reaches 80.3%.Calcite,on the other hand,exhibits a recovery rate of 17.6%,indicating a significant difference in floatability between the two minerals.Subsequently,the surface modifica-tions of scheelite and calcite following LUT treatment are characterized using adsorption capacity testing,Zeta potential analysis,Fourier transform infrared spectroscopy(FT-IR),X-ray photoelectron spectroscopy(XPS),and atomic force microscopy(AFM).The study in-vestigates the selective depressant mechanism of LUT on calcite.Adsorption capacity testing and Zeta potential analysis demonstrate sub-stantial absorption of LUT on the surface of calcite,impeding the further adsorption of sodium oleate,while its impact on scheelite is min-imal.FT-IR and XPS analyses reveal the selective adsorption of LUT onto the surface of calcite,forming strong chemisorption bonds between the hydroxyl group and calcium ions present.AFM directly illustrates the distinct adsorption densities of LUT on the two miner-al types.Consequently,LUT can effectively serve as a depressant for calcite,enabling the successful separation of scheelite and calcite.
基金Supported by the National Key Research and Development Program of China(No.2022YFC3103602)the National Natural Science Foundation of China(No.41976147)+4 种基金the NSFC-Shandong Joint Fund(No.U 2106208)the Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(No.GML2019ZD0402)the National Key Research and Development Program of China(No.2018FY100105)the Innovation Academy of South China Sea Ecology and Environmental Engineering,Chinese Academy of Sciences(No.ISEE2021ZD03)the Science and Technology Planning Project of Guangdong Province,China(No.2020B1212060058)。
文摘Thermal stress causes the overproduction and toxic accumulation of reactive oxygen species(ROS),which seems to be correlated with coral bleaching and,ultimately,death.The reduction of ROS concentration within the coral holobiont could minimize the effects of thermal stress and support efforts to reduce coral decline globally.In the current study,we explored the physiological responses of Pocillopora damicornis to ROS-scavenging bacteria inoculation as well as the microbiome restructuring that correlates with P.damicornis’s resilience to thermal stress after probiotic inoculation.Inoculation of corals with ROS-scavenging bacteria enhanced coral health and reduced ROS concentration.Furthermore,the enhanced coral thermal resistance promoted by ROS-scavenging bacteria was also correlated with an overall coral microbiome restructuring.In addition,the complex network relationships between bacteria and Symbiodiniaceae in corals after ROS-scavenging bacteria inoculation contributed to corals’resilience to high temperatures.Besides,coral heat tolerance bacterial biomarkers,such as Myxococcota,were enriched in corals with added ROS-scavenging bacteria.Collectively,our findings validate the selected ROS-scavenging bacteria as coral probiotics that could help corals resist thermal stress on a short timescale.Additionally,our data contribute to our understanding of the potential interactions between different members of the coral holobiont and the use of probiotics as tools to aid coral restoration efforts.
基金supported by the National Key Research and Development Project(Grant No.2018YFC2001100).
文摘The matrix thermal properties have an important impact on laser-induced plasma,as the thermal effect dominates the interaction between ns-pulsed laser and matter,especially in metals.We used a series of pure metals and aluminum alloys to measure plasma temperature and electron density through laser-induced breakdown spectroscopy,in order to investigate the effect of matrix thermal properties on laser-induced plasma.In pure metals,a significant negative linear correlation was observed between the matrix thermal storage coefficient and plasma temperature,while a weak correlation was observed with electron density.The results indicate that metals with low thermal conductivity or specific heat capacity require less laser energy for thermal diffusion or melting and evaporation,resulting in higher ablation rates and higher plasma temperatures.However,considering ionization energy,thermal effects may be a secondary factor affecting electron density.The experiment of aluminum alloy further confirms the influence of thermal conductivity on plasma temperature and its mechanism explanation.
基金National Key R&D Program of China,Grant/Award Number:2021YFF0500700Fundamental Research Funds for the Central Universities,Grant/Award Numbers:30921013103,30920041113+1 种基金Jiangsu Natural Science Foundation,Grant/Award Number:BK20190460National Natural Science Foundation of China,Grant/Award Numbers:51888103,52006105,92163124。
文摘Industrial CO_(2)electroreduction has received tremendous attentions for resolution of the current energy and environmental crisis,but its performance is greatly limited by mass transport at high current density.In this work,an ion‐polymer‐modified gas‐diffusion electrode is used to tackle this proton limit.It is found that gas diffusion electrode‐Nafion shows an impressive performance of 75.2%Faradaic efficiency in multicarbon products at an industrial current density of 1.16 A/cm^(2).Significantly,in‐depth electrochemical characterizations combined with in situ Raman have been used to determine the full workflow of protons,and it is found that HCO_(3)^(−)acts as a proton pool near the reaction environment,and HCO_(3)^(−)and H_(3)O^(+)are local proton donors that interact with the proton shuttle−SO_(3)^(−)from Nafion.With rich proton hopping sites that decrease the activation energy,a“Grotthuss”mechanism for proton transport in the above system has been identified rather than the“Vehicle”mechanism with a higher energy barrier.Therefore,this work could be very useful in terms of the achievement of industrial CO_(2)reduction fundamentally and practically.
基金the National Natural Science Foundation of China(Nos.52272046,52090030,52090031,52122301,51973191)the Natural Science Foundation of Zhejiang Province(LR23E020003)+4 种基金Shanxi-Zheda Institute of New Materials and Chemical Engineering(2021SZ-FR004,2022SZ-TD011,2022SZ-TD012,2022SZ-TD014)Hundred Talents Program of Zhejiang University(188020*194231701/113,112300+1944223R3/003,112300+1944223R3/004)the Fundamental Research Funds for the Central Universities(Nos.226-2023-00023,226-2023-00082,2021FZZX001-17,K20200060)National Key R&D Program of China(NO.2022YFA1205300,NO.2022YFA1205301,NO.2020YFF0204400,NO.2022YFF0609801)“Pioneer”and“Leading Goose”R&D Program of Zhejiang 2023C01190.
文摘Highly thermally conductive graphitic film(GF)materials have become a competitive solution for the thermal management of high-power electronic devices.However,their catastrophic structural failure under extreme alternating thermal/cold shock poses a significant challenge to reliability and safety.Here,we present the first investigation into the structural failure mechanism of GF during cyclic liquid nitrogen shocks(LNS),which reveals a bubbling process characterized by“permeation-diffusion-deformation”phenomenon.To overcome this long-standing structural weakness,a novel metal-nanoarmor strategy is proposed to construct a Cu-modified graphitic film(GF@Cu)with seamless heterointerface.This well-designed interface ensures superior structural stability for GF@Cu after hundreds of LNS cycles from 77 to 300 K.Moreover,GF@Cu maintains high thermal conductivity up to 1088 W m^(−1)K^(−1)with degradation of less than 5%even after 150 LNS cycles,superior to that of pure GF(50%degradation).Our work not only offers an opportunity to improve the robustness of graphitic films by the rational structural design but also facilitates the applications of thermally conductive carbon-based materials for future extreme thermal management in complex aerospace electronics.
基金National Natural Science Foundation of China(Nos.12272283,12172266).
文摘The Mean First-Passage Time (MFPT) and Stochastic Resonance (SR) of a stochastic tumor-immune model withnoise perturbation are discussed in this paper. Firstly, considering environmental perturbation, Gaussian whitenoise and Gaussian colored noise are introduced into a tumor growth model under immune surveillance. Asfollows, the long-time evolution of the tumor characterized by the Stationary Probability Density (SPD) and MFPTis obtained in theory on the basis of the Approximated Fokker-Planck Equation (AFPE). Herein the recurrenceof the tumor from the extinction state to the tumor-present state is more concerned in this paper. A moreefficient algorithmof Back-Propagation Neural Network (BPNN) is utilized in order to testify the correction of thetheoretical SPDandMFPT.With the existence of aweak signal, the functional relationship between Signal-to-NoiseRatio (SNR), noise intensities and correlation time is also studied. Numerical results show that both multiplicativeGaussian colored noise and additive Gaussian white noise can promote the extinction of the tumors, and themultiplicative Gaussian colored noise can lead to the resonance-like peak on MFPT curves, while the increasingintensity of the additiveGaussian white noise results in theminimum of MFPT. In addition, the correlation timesare negatively correlated with MFPT. As for the SNR, we find the intensities of both the Gaussian white noise andthe Gaussian colored noise, as well as their correlation intensity can induce SR. Especially, SNR is monotonouslyincreased in the case ofGaussian white noisewith the change of the correlation time.At last, the optimal parametersin BPNN structure are analyzed for MFPT from three aspects: the penalty factors, the number of neural networklayers and the number of nodes in each layer.
基金National Key Research and Development Program,Grant/Award Number:2019YFA0903800,2021YFA0805701,2021YFA0805905 and 2022YFA1103603CAS Project for Young Scientists in Basic Research,Grant/Award Number:YSBR-012+2 种基金STI 2030-Major Project,Grant/Award Number:2023ZD0407503National Natural Science Foundation of China,Grant/Award Number:32071456 and 82241224Strategic Priority Research Program of the Chinese Academy of Sciences,Grant/Award Number:XDA16030000。
文摘Background:Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic,while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs.Current knockout strategies are mainly aimed at the genes causing hyperacute immune rejection(HAR)that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure,in which process the MHCⅡmolecule plays critical roles.Methods:Thus,we generate a 4-gene(GGTA1,CMAH,β4GalNT2,and CIITA)knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously.Results:We successfully obtained 4KO piglets with deficiency in all alleles of genes,and at cellular and tissue levels.Additionally,the safety of our animals after gene editing was verified by using whole-genome sequencing and karyotyping.Piglets have survived for more than one year in the barrier,and also survived for more than 3 months in the conventional environment,suggesting that the piglets without MHCⅡcan be raised in the barrier and then gradually mated in the conventional environment.Conclusions:4KO piglets have lower immunogenicity,are safe in genomic level,and are easier to breed than the model with both MHCⅠandⅡdeletion.
