Invasive exotic （alien） species have not been taken into enough consideration concerning the European Water Framework Directive （WFD） and other European directives until recently. The Dutch ministry responsible fo...Invasive exotic （alien） species have not been taken into enough consideration concerning the European Water Framework Directive （WFD） and other European directives until recently. The Dutch ministry responsible for water management is looking for ways to establish the impacts that invasive alien species may have on specified water types. This paper concentrates on the vulnerability of such water types to the introduction of exotic species. This new approach focusses on the system where the alien species are introduced into rather than only on the alien species themselves. We propose an equation that combines threats to and in water types with effects of particular species （observed or prognosticated）. Numerical values used in the formula have been found by scoring a number of properties in different water types and species, which are specified in questionnaires. The results of the calculations are given as relative vulnerability scores （scale 1-10）. By testing as many as 8 water types and 13 species, we demonstrate that this method is flexible and easy to use for water managers. Our results can be translated into classes of vulner- ability, which are represented on geographical maps with colour codes to indicate different degrees of vulnerability in the different water bodies. This readily corresponds to the way countries are required to report to the European Union in the context of the WFD. The method can also be generalized using functional groups of （exotic） species instead of particular species展开更多
Introduction: Lyell’s syndrome (SL), called Toxic Epidermal Necrolysis is one of the most serious forms of medication accidents. It is an acute, rare pathology, its incidence is estimated at 1 to 2 cases out of one m...Introduction: Lyell’s syndrome (SL), called Toxic Epidermal Necrolysis is one of the most serious forms of medication accidents. It is an acute, rare pathology, its incidence is estimated at 1 to 2 cases out of one million inhabitants per year and its evolution can be fatal. Materials and Methods: We report the observation of a 60-year-old patient, with no significant pathological history, admitted to our intensive care unit at the Renaissance University Teaching Hospital in N’Djamena for the treatment of Toxic Epidermal Necrolysis. In whom the onset of symptoms dates back to few hours after vaccination against COVID-19 with Ag Johnson and Johnson. Results: An ophthalmology opinion was requested and the patient was put on Fucithalmic. In our case, in addition to the advanced age of the patient (60 years old), her SCORTEN was ≥5. Conclusion: The late management as well as the absence of a specific department for severe burns, which condition the presence of a technical plate was fatal to her despite multidisciplinary care: Resuscitators, Traumato-Orthopedist and ophthalmologist.展开更多
Although the relationship between anesthesia and consciousness has been investigated for decades, our understanding of the underlying neural mechanisms of anesthesia and consciousness remains rudimentary, which limits...Although the relationship between anesthesia and consciousness has been investigated for decades, our understanding of the underlying neural mechanisms of anesthesia and consciousness remains rudimentary, which limits the development of systems for anesthesia monitoring and consciousness evaluation. Moreover, the current practices for anesthesia monitoring are mainly based on methods that do not provide adequate information and may present obstacles to the precise application of anesthesia. Most recently, there has been a growing trend to utilize brain network analysis to reveal the mechanisms of anesthesia, with the aim of providing novel insights to promote practical application. This review summarizes recent research on brain network studies of anesthesia, and compares the underlying neural mechanisms of consciousness and anesthesia along with the neural signs and measures of the distinct aspects of neural activity. Using the theory of cortical fragmentation as a starting point, we introduce important methods and research involving connectivity and network analysis. We demonstrate that whole-brain multimodal network data can provide important supplementary clinical information. More importantly, this review posits that brain network methods, if simplified, will likely play an important role in improving the current clinical anesthesia monitoring systems.展开更多
Nine new fluorine-containing drugs have been approved by the US Food and Drug Administration(FDA)in 2021,which are presented in this review article.These small molecular drugs feature aromatic fluorine,trifluoromethyl...Nine new fluorine-containing drugs have been approved by the US Food and Drug Administration(FDA)in 2021,which are presented in this review article.These small molecular drugs feature aromatic fluorine,trifluoromethyl and chlorodifluoro groups.The therapeutic areas of these fluorine-containing drugs include multiple myeloma,lymphoma,HIV,chronic heart failure,chronic myeloid leukemia,(ANCA)-associated vasculitis,migraines,von Hippel-Lindau disease,and non-small cell lung cancer.The brief biological activities and the synthetic methods have been discussed in this review for each of these nine drugs.展开更多
Aim: This study aimed at describing the various aspects of complications of circumcision and their management in patients referred to N’Djamena Mother & Child Hospital (Chad). Material and Methods: All patients r...Aim: This study aimed at describing the various aspects of complications of circumcision and their management in patients referred to N’Djamena Mother & Child Hospital (Chad). Material and Methods: All patients referred for complications of circumcision reported on a 3-year period (July 2011-May 2014) were included. Demographic data, circumstances of the circumcision, clinical presentation and management were computed. Results: Thirty-one cases of complications from traditionally performed circumcisions (n = 19) or circumcisions were performed by paramedics (n = 12). The average age was 7.5 ± 2 years. More than 60% of the patients were between 6 and 10 years old. The complications reported included: urethral fistula in the balano preputial sulcus in 10 cases (32%), entire amputation of the glans in 2 cases (6.5%), amputation of the penis in one case (3.5%), stenosis of the urethral meatus in 8 cases (26%), bleeding in 5 cases (16%) and infections in 5 cases (16%). A surgical treatment was performed according to clinical cases. Conclusion: Circumcision is safe when performed in hospitals. Unfortunately, serious complications may occur if it is performed by non-experts. Hence there is a necessity to raise people’s awareness on the importance of the medicalization of circumcision.展开更多
Lanthanide-doped upconversion nanoparticles(UCNPs)can absorb near-infrared photons and convert them into visible and ultraviolet emissions.These nanomaterials possess extraordinary optical performance and hold potenti...Lanthanide-doped upconversion nanoparticles(UCNPs)can absorb near-infrared photons and convert them into visible and ultraviolet emissions.These nanomaterials possess extraordinary optical performance and hold potential as active platforms for a variety of technological applications.The ability to fabricate highly ordered nanoparticle-based photonic elements over a large area is of fundamental significance for luminescence tuning.Despite all the efforts made,however,large-area spatial patterning of UCNPs into ordered arrays with high controllability remains a challenge.In this study,we report a highthroughput strategy to pattern optical nanomaterials through the use of polymer microspheres and templated assembly of UCNPs.This technique utilizes capillary force to drive hybrid clusters into the physical template,resulting in large-area,spatially ordered arrays of particles.The findings reported in this work may promote the development of novel nonlinear optical devices,such as solid-state laser arrays,high-density optical storage,and anti-counterfeiting labels.展开更多
Suppose R is a commutative ring with 1, and 2 is a unit of R. Let Tn(R) be the n × n upper triangular matrix modular over R, and let (?)i(R) (i=2 or 3) be the set of all R-module automorphisms on Tn(R) that prese...Suppose R is a commutative ring with 1, and 2 is a unit of R. Let Tn(R) be the n × n upper triangular matrix modular over R, and let (?)i(R) (i=2 or 3) be the set of all R-module automorphisms on Tn(R) that preserve involutory or tripotent. The main result in this paper is that f ∈ (?)i(R) if and only if there exists an invertible matrix U ∈ Tn(R) and orthogonal idempotent elements e1,e2,e3 ande4 in R with such that where展开更多
CONSPECTUS:Functional and structural studies of ion channels have deepened our understanding of their mechanisms and important role in regulating neuronal activity and treating disease.Manipulation of ion channels can...CONSPECTUS:Functional and structural studies of ion channels have deepened our understanding of their mechanisms and important role in regulating neuronal activity and treating disease.Manipulation of ion channels can directly control electrochemical signals in the nervous and cardiovascular systems for advanced neuromodulation and theranostics.Manipulation tools based on ion channel control,such as optogenetics,electrical stimulation,chemogenetics,and gene editing,have advanced basic biomedical research and enabled unprecedented treatment strategies.Nevertheless,conventional approaches are associated with limitations such as invasiveness,irreversibility,or low spatiotemporal resolution,which limit their clinical application.Therefore,targeted noninvasive or minimally invasive modulation of various ion channel activities is highly desirable.展开更多
The World Health Organization(WHO)has declared the outbreak of 2019 novel coronavirus,known as 2019-nCoV,a pandemic,as the coronavirus has now infected over 2.6 million people globally and caused more than 185,000 fat...The World Health Organization(WHO)has declared the outbreak of 2019 novel coronavirus,known as 2019-nCoV,a pandemic,as the coronavirus has now infected over 2.6 million people globally and caused more than 185,000 fatalities as of April 23,2020.Coronavirus disease 2019(COVID-19)causes a respiratory illness with symptoms such as dry cough,fever,sudden loss of smell,and,in more severe cases,difficulty breathing.To date,there is no specific vaccine or treatment proven effective against this viral disease.Early and accurate diagnosis of COVID-19 is thus critical to curbing its spread and improving health outcomes.Reverse transcription-polymerase chain reaction(RT-PCR)is commonly used to detect the presence of COVID-19.Other techniques,such as recombinase polymerase amplification(RPA),loopmediated isothermal amplification(LAMP),clustered regularly interspaced short palindromic repeats(CRISPR),and microfluidics,have allowed better disease diagnosis.Here,as part of the effort to expand screening capacity,we review advances and challenges in the rapid detection of COVID-19 by targeting nucleic acids,antigens,or antibodies.We also summarize potential treatments and vaccines against COVID-19 and discuss ongoing clinical trials of interventions to reduce viral progression.展开更多
The healing of diabetic wounds is primarily hindered by persistent inflammation and excessive oxidative stress,increasing the risks of amputation and sepsis.Strategies based on bioactive substances,including recombina...The healing of diabetic wounds is primarily hindered by persistent inflammation and excessive oxidative stress,increasing the risks of amputation and sepsis.Strategies based on bioactive substances,including recombinant growth factors and histatin proteins(Hsts),have been shown to promote skin-related cell migration,anti-inflammation,angiogenesis,and collagen deposition;however,their long-term stability remains a challenge.Herein,a platelet membrane-coated nanoparticle(PNP)system is proposed to achieve enhanced retention of aggregation-induced emissive(AIE)molecular-modified Hst1(Hst1-AIE@PNPs)for more efficient repair of diabetic wounds.The Hst1-AIE@PNPs can not only protect Hst1 from degradation in the wound microenvironment but also permit visual monitoring of the controlled release of Hst1 through enhanced fluorescence in the enriched site.Combined with the antioxidant and anti-inflammatory properties of Hst1,Hst1-AIE@PNPs can effectively adsorb inflammation-related factors and further promote re-epithelialization and collagen deposition,thus achieving high-quality wound repair.The results highlight the potential of highly stable aggregation-induced-emissionfunctionalized Hst1 coated with platelet vesicles as a therapeutic platform to promote diabetic wound-related tissue restoration processes.展开更多
Plants use hydrogen peroxide(H_(2)O_(2))and variation potential(VP)waves as well as chemical transport by transpiration-driven xylem flow to facilitate cell signaling,cell-to-cell communication,and adaptation to envir...Plants use hydrogen peroxide(H_(2)O_(2))and variation potential(VP)waves as well as chemical transport by transpiration-driven xylem flow to facilitate cell signaling,cell-to-cell communication,and adaptation to environmental stresses.The underlying mechanisms and complex interplay among H_(2)O_(2),VP,and transpiration are not clearly understood because of the lack of bioengineering tools for continuous in planta monitoring of the dynamic biological processes.Here,we tackle the challenge by developing microfibershaped organic electrochemical transistors(fOECTs)that can be threaded into the plants.The sensorized microfiber revealed that both H_(2)O_(2)and VP waves propagate faster toward the leaves than toward the roots because of the directional long-distance transport of H_(2)O_(2)in the xylem.In addition,the revealed interplays among VP,H_(2)O_(2),and xylem flow strongly suggest a transpiration-and intensity-dependent H_(2)O_(2)-VP mutual-reinforcing propagation mechanism.The microfiber electronics offer a versatile platform for the in situ study of dynamic physiological processes in plants with high temporospatial resolution.展开更多
The non-destructive operation of intelligent underwater robotics with human-like sensory capabilities is essential for deep-sea resource exploration.However,extreme deep-sea hydrostatic pressure easily distorts sensor...The non-destructive operation of intelligent underwater robotics with human-like sensory capabilities is essential for deep-sea resource exploration.However,extreme deep-sea hydrostatic pressure easily distorts sensor signals or damages devices,and detecting hundred-pascal-level contact forces under tens-of-megapascal hydrostatic pressures presents a critical challenge that hinders the advancement of underwater tactile sensing technology.Inspired by deep-sea sponges’hydrostatic skeletal supporting mechanisms,we developed a fully open-pore hydrophobic ionogel as the sensing layer to construct a biomimetic deep-sea tactile sensor.The contact force is converted into electrical signals for object classification and non-destructive manipulation of marine organisms.This innovative sensing layer features aquatic stability and a pore structure balancing internal-external hydrostatic pressure,reducing environmental disturbances.The sensor maintains stable contact force detection under 50 MPa hydrostatic pressure,and accurately classify objects of varying hardness with an overall recognition accuracy of 95.5%,holding great potential for deep-sea exploration and sustainable resource exploitation.展开更多
Legume rhizobium symbiosis is initiated upon perception of bacterial secreted lipo-chitooligosaccharides （LCOs）. Perception of these signals by the plant initiates a signaling cascade that leads to nodule formation....Legume rhizobium symbiosis is initiated upon perception of bacterial secreted lipo-chitooligosaccharides （LCOs）. Perception of these signals by the plant initiates a signaling cascade that leads to nodule formation. Several studies have implicated a function for cytokinin in this process. However, whether cytokinin accu- mulation and subsequent signaling are an integral part of rhizobium LCO signaling remains elusive. Here, we show that cytokinin signaling is required for the majority of transcriptional changes induced by rhizo- bium LCOs. In addition, we demonstrate that several cytokinins accumulate in the root susceptible zone 3 h after rhizobium LCO application, including the biologically most active cytokinins, trans-zeatin and iso- pentenyl adenine. These responses are dependent on calcium- and calmodulin-dependent protein kinase （CCaMK）, a key protein in rhizobial LCO-induced signaling. Analysis of the ethylene-insensitive Mtein21 Mtsickle mutant showed that LCO-induced cytokinin accumulation is negatively regulated by ethylene. Together with transcriptional induction of ethylene biosynthesis genes, it suggests a feedback loop negatively regulating LCO signaling and subsequent cytokinin accumulation. We argue that cytokinin accumulation is a key step in the pathway leading to nodule organogenesis and that this is tightly controlled by feedback loops.展开更多
Growth charts describe growth curves at various percentiles that illustrate the distribution of body measurements in children.Over many decades, growth charts have been an invaluable reference for public health worker...Growth charts describe growth curves at various percentiles that illustrate the distribution of body measurements in children.Over many decades, growth charts have been an invaluable reference for public health workers and clinicians to track and evaluate the developmental status of children and to detect abnormal growth for early intervention. Since growth charts were published,they have been greatly detailed in different age, gender, and ethnicity groups.展开更多
While doxorubicin(DOX)is one of the most common chemotherapeutic drugs for treating cancer,use of DOX must be managed carefully due to dose-related toxicity.Nanodiamond(ND)drug delivery system conjugated with DOX(NDX)...While doxorubicin(DOX)is one of the most common chemotherapeutic drugs for treating cancer,use of DOX must be managed carefully due to dose-related toxicity.Nanodiamond(ND)drug delivery system conjugated with DOX(NDX)has been reported to enhance treatment efficacy and attenuate toxicity in murine cancer models.In addition,extensive biocompatibility studies indicate that NDs seem to be well tolerated in non-human primates.Before the clinical translation of NDX,it is necessary to verify the safety of ND in large mammals.Studies of nanomedicine drug safety for large animal are not commonly reported,and this work represents a key milestone in bridging earlier advances towards clinical assessment.Herein,NDs’safety as a drug-delivery platform was evaluated in Naïve Beagle dogs.The study is performed with DOX,ND,and NDX in a dual-gender animal model using intravenous(IV)injection and hepatic portal vein(HPV)injection methods.The dogs are monitored for their health phenotype changes in continuous 5 days.Blood and urine obtained are for clinical pathology research.The results indicate that ND drug delivery platform significantly relieves DOX toxicity for Naïve Beagle dog model.This study provides guidance for the pre-clinical safety assessment of NDX therapy at large animal level.展开更多
Background:Vascular inflow occlusion(VIO)during liver resections(Pringle manoeuvre)can be applied to reduce blood loss,however may at the same time,give rise to ischemia-reperfusion injury(IRI).The aim of this study w...Background:Vascular inflow occlusion(VIO)during liver resections(Pringle manoeuvre)can be applied to reduce blood loss,however may at the same time,give rise to ischemia-reperfusion injury(IRI).The aim of this study was to assess the characteristics of hepatic microvascular perfusion during VIO in patients undergoing major liver resection.Methods:Assessment of hepatic microcirculation was performed using a handheld vital microscope(HVM)at the beginning of surgery,end of VIO(20 minutes)and during reperfusion after the termination of VIO.The microcirculatory parameters assessed were:functional capillary density(FCD),microvascular flow index(MFI)and sinusoidal diameter(SinD).Results:A total of 15 patients underwent VIO;8 patients showed hepatic microvascular perfusion despite VIO(partial responders)and 7 patients showed complete cessation of hepatic microvascular perfusion(full responders).Functional microvascular parameters and blood flow levels were significantly higher in the partial responders when compared to the full responders during VIO(FCD:0.84±0.88 vs.0.00±0.00 mm/mm2,P<0.03,respectively,and MFI:0.69–0.22 vs.0.00±0.00,P<0.01,respectively).Conclusions:An interpatient heterogeneous response in hepatic microvascular blood flow was observed upon VIO.This may explain why clinical strategies to protect the liver against IRI lacked consistency.展开更多
Protein phosphatase 2A （PP2A） accounts for the majority of total Ser/Thr phosphatase activities in most cell types and regulates many biological processes. PP2A holoenzymes contain a scaffold A subunit, a cat- alyti...Protein phosphatase 2A （PP2A） accounts for the majority of total Ser/Thr phosphatase activities in most cell types and regulates many biological processes. PP2A holoenzymes contain a scaffold A subunit, a cat- alytic C subunit, and one of the regulatory/targeting B subunits. How the B subunit controls PP2A localization and substrate specificity, which is a crucial aspect of PP2A regulation, remains poorly understood. The kine- tochore is a critical site for PP2A functioning, where PP2A orchestrates chromosome segregation through its interactions with BubR1. The PP2A-BubR1 interac- tion plays important roles in both spindle checkpoint silencing and stable microtubule-kinetochore attach- ment. Here we present the crystal structure of a PP2A B56-BubRI complex, which demonstrates that a con- served BubRl LxxlxE motif binds to the concave side of the B56 pseudo-HEAT repeats. The BubR1 motif binds to a groove formed between B56 HEAT repeats 3 and 4, which is quite distant from the B56 binding surface for PP2A catalytic C subunit and thus is unlikely to affect PP2A activity. In addition, the BubR1 binding site on B56 is far from the B56 binding site of shugoshin, another kinetochore PP2A-binding protein, and thus BubR1 and shugoshin can potentially interact with PP2A-B56 simultaneously. Our structural and biochemical analysis indicates that other proteins with the LxxlxE motif may also bind to the same PP2A B56 surface. Thus, our structure of the PP2A B56-BubR1 complex provides important insights into how the B56 subunit directs the recruitment of PP2A to specific targets.展开更多
Wireless and battery-free radio-frequency(RF)sensors can be used to create physical spaces that ambiently sense and respond to human activities.Making such sensors ultra-flexible and transparent is important to preser...Wireless and battery-free radio-frequency(RF)sensors can be used to create physical spaces that ambiently sense and respond to human activities.Making such sensors ultra-flexible and transparent is important to preserve the aesthetics of living environments,accommodate daily activities,and functionally integrate with objects.However,existing RF sensors are unable to simultaneously achieve high transparency,flexibility,and the electrical conductivity required for remote room-scale operation.Here,we report 4.5μm RF tag sensors achieving transparency exceeding 90%that provide capabilities in room-scale ambient wireless sensing.We develop a laser-assisted water-based adhesion-reversion process to digitally realize computer-aided RF design at scale.By individually tagging multiple objects and regions of the human body,we demonstrate multiplexed wireless tracking of humanenvironment interactions and physiological signals at a range of up to 8m.These radio-frequency identification sensors open opportunities for non-intrusive wireless sensing of daily living spaces for applications in health monitoring and elderly care.展开更多
Using photodynamic therapy(PDT)to treat deep-seated cancers is limited due to inefficient delivery of photosensitizers and low tissue penetration of light.Polymeric nanocarriers are widely used for photosensitizer del...Using photodynamic therapy(PDT)to treat deep-seated cancers is limited due to inefficient delivery of photosensitizers and low tissue penetration of light.Polymeric nanocarriers are widely used for photosensitizer delivery,while the self-quenching of the encapsulated photosensitizers would impair the PDT efficacy.Furthermore,the generated short-lived reactive oxygen spieces(ROS)can hardly diffuse out of nanocarriers,resulting in low PDT efficacy.Therefore,a smart nanocarrier system which can be degraded by light,followed by photosensitizer activation can potentially overcome these limitations and enhance the PDT efficacy.A light-sensitive polymer nanocarrier encapsulating photosensitizer(RB-M)was synthesized.An implantable wireless dual wavelength microLED device which delivers the two light wavelengths sequentially was developed to programmatically control the release and activation of the loaded photosensitizer.Two transmitter coils with matching resonant frequencies allow activation of the connected LEDs to emit different wavelengths independently.Optimal irradiation time,dose,and RB-M concentration were determined using an agent-based digital simulation method.In vitro and in vivo validation experiments in an orthotopic rat liver hepatocellular carcinoma disease model confirmed that the nanocarrier rupture and sequential low dose light irradiation strategy resulted in successful PDT at reduced photosensitizer and irradiation dose,which is a clinically significant event that enhances treatment safety.展开更多
文摘Invasive exotic （alien） species have not been taken into enough consideration concerning the European Water Framework Directive （WFD） and other European directives until recently. The Dutch ministry responsible for water management is looking for ways to establish the impacts that invasive alien species may have on specified water types. This paper concentrates on the vulnerability of such water types to the introduction of exotic species. This new approach focusses on the system where the alien species are introduced into rather than only on the alien species themselves. We propose an equation that combines threats to and in water types with effects of particular species （observed or prognosticated）. Numerical values used in the formula have been found by scoring a number of properties in different water types and species, which are specified in questionnaires. The results of the calculations are given as relative vulnerability scores （scale 1-10）. By testing as many as 8 water types and 13 species, we demonstrate that this method is flexible and easy to use for water managers. Our results can be translated into classes of vulner- ability, which are represented on geographical maps with colour codes to indicate different degrees of vulnerability in the different water bodies. This readily corresponds to the way countries are required to report to the European Union in the context of the WFD. The method can also be generalized using functional groups of （exotic） species instead of particular species
文摘Introduction: Lyell’s syndrome (SL), called Toxic Epidermal Necrolysis is one of the most serious forms of medication accidents. It is an acute, rare pathology, its incidence is estimated at 1 to 2 cases out of one million inhabitants per year and its evolution can be fatal. Materials and Methods: We report the observation of a 60-year-old patient, with no significant pathological history, admitted to our intensive care unit at the Renaissance University Teaching Hospital in N’Djamena for the treatment of Toxic Epidermal Necrolysis. In whom the onset of symptoms dates back to few hours after vaccination against COVID-19 with Ag Johnson and Johnson. Results: An ophthalmology opinion was requested and the patient was put on Fucithalmic. In our case, in addition to the advanced age of the patient (60 years old), her SCORTEN was ≥5. Conclusion: The late management as well as the absence of a specific department for severe burns, which condition the presence of a technical plate was fatal to her despite multidisciplinary care: Resuscitators, Traumato-Orthopedist and ophthalmologist.
基金supported by the Zhejiang Provincial Natural Science Foundation of China(LGF19H090023)the National Natural Science Foundation of China(81801785 and 82172056)+5 种基金the National Key Research and Development Program of China(2019YFC1711800)the Key Research and Development Program of Shanxi(2020ZDLSF04-03)This work was partly supported by the grants from the Zhejiang Lab(2019KE0AD01 and 2021KE0AB04)the Zhejiang University Global Partnership Fund(100000-11320)the Shanghai Municipal Science and Technology Major Project(2021SHZDZX0100)the Fundamental Research Funds for the Central Universities.
文摘Although the relationship between anesthesia and consciousness has been investigated for decades, our understanding of the underlying neural mechanisms of anesthesia and consciousness remains rudimentary, which limits the development of systems for anesthesia monitoring and consciousness evaluation. Moreover, the current practices for anesthesia monitoring are mainly based on methods that do not provide adequate information and may present obstacles to the precise application of anesthesia. Most recently, there has been a growing trend to utilize brain network analysis to reveal the mechanisms of anesthesia, with the aim of providing novel insights to promote practical application. This review summarizes recent research on brain network studies of anesthesia, and compares the underlying neural mechanisms of consciousness and anesthesia along with the neural signs and measures of the distinct aspects of neural activity. Using the theory of cortical fragmentation as a starting point, we introduce important methods and research involving connectivity and network analysis. We demonstrate that whole-brain multimodal network data can provide important supplementary clinical information. More importantly, this review posits that brain network methods, if simplified, will likely play an important role in improving the current clinical anesthesia monitoring systems.
基金the financial support from the National Natural Science Foundation of China(No.21761132021)the Qing-Lan Project of Jiangsu Province(for Han)IKERBASQUE,Basque Foundation for Science(for Soloshonok)。
文摘Nine new fluorine-containing drugs have been approved by the US Food and Drug Administration(FDA)in 2021,which are presented in this review article.These small molecular drugs feature aromatic fluorine,trifluoromethyl and chlorodifluoro groups.The therapeutic areas of these fluorine-containing drugs include multiple myeloma,lymphoma,HIV,chronic heart failure,chronic myeloid leukemia,(ANCA)-associated vasculitis,migraines,von Hippel-Lindau disease,and non-small cell lung cancer.The brief biological activities and the synthetic methods have been discussed in this review for each of these nine drugs.
文摘Aim: This study aimed at describing the various aspects of complications of circumcision and their management in patients referred to N’Djamena Mother & Child Hospital (Chad). Material and Methods: All patients referred for complications of circumcision reported on a 3-year period (July 2011-May 2014) were included. Demographic data, circumstances of the circumcision, clinical presentation and management were computed. Results: Thirty-one cases of complications from traditionally performed circumcisions (n = 19) or circumcisions were performed by paramedics (n = 12). The average age was 7.5 ± 2 years. More than 60% of the patients were between 6 and 10 years old. The complications reported included: urethral fistula in the balano preputial sulcus in 10 cases (32%), entire amputation of the glans in 2 cases (6.5%), amputation of the penis in one case (3.5%), stenosis of the urethral meatus in 8 cases (26%), bleeding in 5 cases (16%) and infections in 5 cases (16%). A surgical treatment was performed according to clinical cases. Conclusion: Circumcision is safe when performed in hospitals. Unfortunately, serious complications may occur if it is performed by non-experts. Hence there is a necessity to raise people’s awareness on the importance of the medicalization of circumcision.
基金Project supported by the Singapore Ministry of Education(MOE2017-T2-2-110)Agency for Science,Technology and Research(A*STAR)(A1883c0011)+2 种基金National Research Foundation,Prime Minister’s Office,Singapore under its Competitive Research Program(NRF-CRP15-2015-03)under the NRF Investigatorship Programme(NRF-NRFI05-2019-0003)National Natural Science Foundation of China(21771135)。
文摘Lanthanide-doped upconversion nanoparticles(UCNPs)can absorb near-infrared photons and convert them into visible and ultraviolet emissions.These nanomaterials possess extraordinary optical performance and hold potential as active platforms for a variety of technological applications.The ability to fabricate highly ordered nanoparticle-based photonic elements over a large area is of fundamental significance for luminescence tuning.Despite all the efforts made,however,large-area spatial patterning of UCNPs into ordered arrays with high controllability remains a challenge.In this study,we report a highthroughput strategy to pattern optical nanomaterials through the use of polymer microspheres and templated assembly of UCNPs.This technique utilizes capillary force to drive hybrid clusters into the physical template,resulting in large-area,spatially ordered arrays of particles.The findings reported in this work may promote the development of novel nonlinear optical devices,such as solid-state laser arrays,high-density optical storage,and anti-counterfeiting labels.
基金Foundation item:The NSF(10271021)of China and NSF(10531130)of Heilongjiang Education Committee
文摘Suppose R is a commutative ring with 1, and 2 is a unit of R. Let Tn(R) be the n × n upper triangular matrix modular over R, and let (?)i(R) (i=2 or 3) be the set of all R-module automorphisms on Tn(R) that preserve involutory or tripotent. The main result in this paper is that f ∈ (?)i(R) if and only if there exists an invertible matrix U ∈ Tn(R) and orthogonal idempotent elements e1,e2,e3 ande4 in R with such that where
基金This work was supported by the National Research Foundation,Prime Minister’s Office,Singapore,under the NRF Investigatorship Programme(Award No.NRF-NRFI05-2019-0003)NUS NANONASH Programme(NUHSRO/2020/002/NanoNash/LOA+2 种基金R143000B43114)Initiation Grant Faculty Niche Research Areas Fund(RC-FNRA-IG/20-21/SCI/02)the Science and Technology Innovation Commission of Shenzhen(RCBS20200714114910141,JCYJ20210324132816039),and the Start-up Grant at Harbin Institute of Technology(Shenzhen),China(HA45001108,HA11409049).
文摘CONSPECTUS:Functional and structural studies of ion channels have deepened our understanding of their mechanisms and important role in regulating neuronal activity and treating disease.Manipulation of ion channels can directly control electrochemical signals in the nervous and cardiovascular systems for advanced neuromodulation and theranostics.Manipulation tools based on ion channel control,such as optogenetics,electrical stimulation,chemogenetics,and gene editing,have advanced basic biomedical research and enabled unprecedented treatment strategies.Nevertheless,conventional approaches are associated with limitations such as invasiveness,irreversibility,or low spatiotemporal resolution,which limit their clinical application.Therefore,targeted noninvasive or minimally invasive modulation of various ion channel activities is highly desirable.
基金This work was supported by the Singapore Ministry of Education(MOE2017-T2-2-110)Agency for Science,Technology and Research(A∗STAR)(A1883c0011 and A1983c0038)+1 种基金National Research Foundation,Prime Minister’s Office,Singapore,under the NRF Investigatorship programme(Award No.NRF-NRFI05-2019-0003)National Natural Science Foundation of China(21771135).
文摘The World Health Organization(WHO)has declared the outbreak of 2019 novel coronavirus,known as 2019-nCoV,a pandemic,as the coronavirus has now infected over 2.6 million people globally and caused more than 185,000 fatalities as of April 23,2020.Coronavirus disease 2019(COVID-19)causes a respiratory illness with symptoms such as dry cough,fever,sudden loss of smell,and,in more severe cases,difficulty breathing.To date,there is no specific vaccine or treatment proven effective against this viral disease.Early and accurate diagnosis of COVID-19 is thus critical to curbing its spread and improving health outcomes.Reverse transcription-polymerase chain reaction(RT-PCR)is commonly used to detect the presence of COVID-19.Other techniques,such as recombinase polymerase amplification(RPA),loopmediated isothermal amplification(LAMP),clustered regularly interspaced short palindromic repeats(CRISPR),and microfluidics,have allowed better disease diagnosis.Here,as part of the effort to expand screening capacity,we review advances and challenges in the rapid detection of COVID-19 by targeting nucleic acids,antigens,or antibodies.We also summarize potential treatments and vaccines against COVID-19 and discuss ongoing clinical trials of interventions to reduce viral progression.
基金supported by the China Postdoctoral Science Foundation(grant number 2023M731548)the National Natural Science Foundation of China(grant numbers 82322042,82102444)+2 种基金the National Key Research and Development Program of China(grant number 2021YFC2302200)the Natural Science Fund of Guangdong Province for Distinguished Young Scholars(grant number 2022B1515020089)the Basic and Applied Basic Research Project of Guangzhou(grant number SL2023A04J01463).
文摘The healing of diabetic wounds is primarily hindered by persistent inflammation and excessive oxidative stress,increasing the risks of amputation and sepsis.Strategies based on bioactive substances,including recombinant growth factors and histatin proteins(Hsts),have been shown to promote skin-related cell migration,anti-inflammation,angiogenesis,and collagen deposition;however,their long-term stability remains a challenge.Herein,a platelet membrane-coated nanoparticle(PNP)system is proposed to achieve enhanced retention of aggregation-induced emissive(AIE)molecular-modified Hst1(Hst1-AIE@PNPs)for more efficient repair of diabetic wounds.The Hst1-AIE@PNPs can not only protect Hst1 from degradation in the wound microenvironment but also permit visual monitoring of the controlled release of Hst1 through enhanced fluorescence in the enriched site.Combined with the antioxidant and anti-inflammatory properties of Hst1,Hst1-AIE@PNPs can effectively adsorb inflammation-related factors and further promote re-epithelialization and collagen deposition,thus achieving high-quality wound repair.The results highlight the potential of highly stable aggregation-induced-emissionfunctionalized Hst1 coated with platelet vesicles as a therapeutic platform to promote diabetic wound-related tissue restoration processes.
基金supported by the Singapore Indoor Farming System(SingFarm)CREATE Initiative(024574-00005)from the National Research Foundation of Singaporea National University of Singapore Presidential Young Professorship Award(22-4974-A0003).
文摘Plants use hydrogen peroxide(H_(2)O_(2))and variation potential(VP)waves as well as chemical transport by transpiration-driven xylem flow to facilitate cell signaling,cell-to-cell communication,and adaptation to environmental stresses.The underlying mechanisms and complex interplay among H_(2)O_(2),VP,and transpiration are not clearly understood because of the lack of bioengineering tools for continuous in planta monitoring of the dynamic biological processes.Here,we tackle the challenge by developing microfibershaped organic electrochemical transistors(fOECTs)that can be threaded into the plants.The sensorized microfiber revealed that both H_(2)O_(2)and VP waves propagate faster toward the leaves than toward the roots because of the directional long-distance transport of H_(2)O_(2)in the xylem.In addition,the revealed interplays among VP,H_(2)O_(2),and xylem flow strongly suggest a transpiration-and intensity-dependent H_(2)O_(2)-VP mutual-reinforcing propagation mechanism.The microfiber electronics offer a versatile platform for the in situ study of dynamic physiological processes in plants with high temporospatial resolution.
基金support from the National Key R&D Program of China(No.2024YFB4707300)the National Natural Science Foundation of China(No.52550004,52188102,52475018)+3 种基金the Fundamental Research Funds for the Central Universities(HUST:YCJJ20242101)the STAR Project by the School of Mechanical Science and Engineering of Huazhong University of Science and Technologysupport from Flexible Electronics Research Center and Analytical and Testing Center of HUST for providing experiment facilitysupport from the National University of Singapore Presidential Young Professorship.
文摘The non-destructive operation of intelligent underwater robotics with human-like sensory capabilities is essential for deep-sea resource exploration.However,extreme deep-sea hydrostatic pressure easily distorts sensor signals or damages devices,and detecting hundred-pascal-level contact forces under tens-of-megapascal hydrostatic pressures presents a critical challenge that hinders the advancement of underwater tactile sensing technology.Inspired by deep-sea sponges’hydrostatic skeletal supporting mechanisms,we developed a fully open-pore hydrophobic ionogel as the sensing layer to construct a biomimetic deep-sea tactile sensor.The contact force is converted into electrical signals for object classification and non-destructive manipulation of marine organisms.This innovative sensing layer features aquatic stability and a pore structure balancing internal-external hydrostatic pressure,reducing environmental disturbances.The sensor maintains stable contact force detection under 50 MPa hydrostatic pressure,and accurately classify objects of varying hardness with an overall recognition accuracy of 95.5%,holding great potential for deep-sea exploration and sustainable resource exploitation.
文摘Legume rhizobium symbiosis is initiated upon perception of bacterial secreted lipo-chitooligosaccharides （LCOs）. Perception of these signals by the plant initiates a signaling cascade that leads to nodule formation. Several studies have implicated a function for cytokinin in this process. However, whether cytokinin accu- mulation and subsequent signaling are an integral part of rhizobium LCO signaling remains elusive. Here, we show that cytokinin signaling is required for the majority of transcriptional changes induced by rhizo- bium LCOs. In addition, we demonstrate that several cytokinins accumulate in the root susceptible zone 3 h after rhizobium LCO application, including the biologically most active cytokinins, trans-zeatin and iso- pentenyl adenine. These responses are dependent on calcium- and calmodulin-dependent protein kinase （CCaMK）, a key protein in rhizobial LCO-induced signaling. Analysis of the ethylene-insensitive Mtein21 Mtsickle mutant showed that LCO-induced cytokinin accumulation is negatively regulated by ethylene. Together with transcriptional induction of ethylene biosynthesis genes, it suggests a feedback loop negatively regulating LCO signaling and subsequent cytokinin accumulation. We argue that cytokinin accumulation is a key step in the pathway leading to nodule organogenesis and that this is tightly controlled by feedback loops.
文摘Growth charts describe growth curves at various percentiles that illustrate the distribution of body measurements in children.Over many decades, growth charts have been an invaluable reference for public health workers and clinicians to track and evaluate the developmental status of children and to detect abnormal growth for early intervention. Since growth charts were published,they have been greatly detailed in different age, gender, and ethnicity groups.
基金The work is partially funded by the National Natural Science Foundation of China(No.81871448)the National Key Research and Development Program of China(Nos.2017YFC0107603 and 2017ZX10203205-006-002)the Medical-Engineering Cross Foundation of Shanghai Jiao Tong University(Nos.YG2017QN52,ZH2018QNA54,and ZH2018QNA49).
文摘While doxorubicin(DOX)is one of the most common chemotherapeutic drugs for treating cancer,use of DOX must be managed carefully due to dose-related toxicity.Nanodiamond(ND)drug delivery system conjugated with DOX(NDX)has been reported to enhance treatment efficacy and attenuate toxicity in murine cancer models.In addition,extensive biocompatibility studies indicate that NDs seem to be well tolerated in non-human primates.Before the clinical translation of NDX,it is necessary to verify the safety of ND in large mammals.Studies of nanomedicine drug safety for large animal are not commonly reported,and this work represents a key milestone in bridging earlier advances towards clinical assessment.Herein,NDs’safety as a drug-delivery platform was evaluated in Naïve Beagle dogs.The study is performed with DOX,ND,and NDX in a dual-gender animal model using intravenous(IV)injection and hepatic portal vein(HPV)injection methods.The dogs are monitored for their health phenotype changes in continuous 5 days.Blood and urine obtained are for clinical pathology research.The results indicate that ND drug delivery platform significantly relieves DOX toxicity for Naïve Beagle dog model.This study provides guidance for the pre-clinical safety assessment of NDX therapy at large animal level.
文摘Background:Vascular inflow occlusion(VIO)during liver resections(Pringle manoeuvre)can be applied to reduce blood loss,however may at the same time,give rise to ischemia-reperfusion injury(IRI).The aim of this study was to assess the characteristics of hepatic microvascular perfusion during VIO in patients undergoing major liver resection.Methods:Assessment of hepatic microcirculation was performed using a handheld vital microscope(HVM)at the beginning of surgery,end of VIO(20 minutes)and during reperfusion after the termination of VIO.The microcirculatory parameters assessed were:functional capillary density(FCD),microvascular flow index(MFI)and sinusoidal diameter(SinD).Results:A total of 15 patients underwent VIO;8 patients showed hepatic microvascular perfusion despite VIO(partial responders)and 7 patients showed complete cessation of hepatic microvascular perfusion(full responders).Functional microvascular parameters and blood flow levels were significantly higher in the partial responders when compared to the full responders during VIO(FCD:0.84±0.88 vs.0.00±0.00 mm/mm2,P<0.03,respectively,and MFI:0.69–0.22 vs.0.00±0.00,P<0.01,respectively).Conclusions:An interpatient heterogeneous response in hepatic microvascular blood flow was observed upon VIO.This may explain why clinical strategies to protect the liver against IRI lacked consistency.
文摘Protein phosphatase 2A （PP2A） accounts for the majority of total Ser/Thr phosphatase activities in most cell types and regulates many biological processes. PP2A holoenzymes contain a scaffold A subunit, a cat- alytic C subunit, and one of the regulatory/targeting B subunits. How the B subunit controls PP2A localization and substrate specificity, which is a crucial aspect of PP2A regulation, remains poorly understood. The kine- tochore is a critical site for PP2A functioning, where PP2A orchestrates chromosome segregation through its interactions with BubR1. The PP2A-BubR1 interac- tion plays important roles in both spindle checkpoint silencing and stable microtubule-kinetochore attach- ment. Here we present the crystal structure of a PP2A B56-BubRI complex, which demonstrates that a con- served BubRl LxxlxE motif binds to the concave side of the B56 pseudo-HEAT repeats. The BubR1 motif binds to a groove formed between B56 HEAT repeats 3 and 4, which is quite distant from the B56 binding surface for PP2A catalytic C subunit and thus is unlikely to affect PP2A activity. In addition, the BubR1 binding site on B56 is far from the B56 binding site of shugoshin, another kinetochore PP2A-binding protein, and thus BubR1 and shugoshin can potentially interact with PP2A-B56 simultaneously. Our structural and biochemical analysis indicates that other proteins with the LxxlxE motif may also bind to the same PP2A B56 surface. Thus, our structure of the PP2A B56-BubR1 complex provides important insights into how the B56 subunit directs the recruitment of PP2A to specific targets.
基金support from the National Institutes of Health(NIH)NIBIB Trailblazer Award(R21-EB029563)NIH R01 Award(R01-EB032959)+1 种基金Office of Naval Research Young Investigator Program Award(N00014-23-1-2391)CDMRP Discovery Award(HT9425-23-1-0041).
文摘Wireless and battery-free radio-frequency(RF)sensors can be used to create physical spaces that ambiently sense and respond to human activities.Making such sensors ultra-flexible and transparent is important to preserve the aesthetics of living environments,accommodate daily activities,and functionally integrate with objects.However,existing RF sensors are unable to simultaneously achieve high transparency,flexibility,and the electrical conductivity required for remote room-scale operation.Here,we report 4.5μm RF tag sensors achieving transparency exceeding 90%that provide capabilities in room-scale ambient wireless sensing.We develop a laser-assisted water-based adhesion-reversion process to digitally realize computer-aided RF design at scale.By individually tagging multiple objects and regions of the human body,we demonstrate multiplexed wireless tracking of humanenvironment interactions and physiological signals at a range of up to 8m.These radio-frequency identification sensors open opportunities for non-intrusive wireless sensing of daily living spaces for applications in health monitoring and elderly care.
基金National Medical Research Council,Singapore (NMRC,MOH-000640,MOH-001114-00)City University of Hong Kong (project number 9380160).
文摘Using photodynamic therapy(PDT)to treat deep-seated cancers is limited due to inefficient delivery of photosensitizers and low tissue penetration of light.Polymeric nanocarriers are widely used for photosensitizer delivery,while the self-quenching of the encapsulated photosensitizers would impair the PDT efficacy.Furthermore,the generated short-lived reactive oxygen spieces(ROS)can hardly diffuse out of nanocarriers,resulting in low PDT efficacy.Therefore,a smart nanocarrier system which can be degraded by light,followed by photosensitizer activation can potentially overcome these limitations and enhance the PDT efficacy.A light-sensitive polymer nanocarrier encapsulating photosensitizer(RB-M)was synthesized.An implantable wireless dual wavelength microLED device which delivers the two light wavelengths sequentially was developed to programmatically control the release and activation of the loaded photosensitizer.Two transmitter coils with matching resonant frequencies allow activation of the connected LEDs to emit different wavelengths independently.Optimal irradiation time,dose,and RB-M concentration were determined using an agent-based digital simulation method.In vitro and in vivo validation experiments in an orthotopic rat liver hepatocellular carcinoma disease model confirmed that the nanocarrier rupture and sequential low dose light irradiation strategy resulted in successful PDT at reduced photosensitizer and irradiation dose,which is a clinically significant event that enhances treatment safety.
