Characterization of cerebrovascular changes in Alzheimer's disease mice by photoacoustic imaging

The cerebral vasculature plays a significant role in the development of Alzheimer's disease(AD),however,the specific association between them remains unclear.In this paper,based on the benefits of photoacoustic imaging(PAI),including label-free,high-resolution,in vivo imaging of vessels,we investigated the structural changes of cerebral vascular in wild-type(WT)mice and AD mice at different ages,analyzed the characteristics of the vascular in different brain regions,and correlated vascular characteristics with cognitive behaviors.The results showed that vascular density and vascular branching index in the cortical and frontal regions of both WT and AD mice decreased with age.Meanwhile,vascular lacunarity increased with age,and the changes in vascular structure were more pronounced in AD mice.The trend of vascular dysfunction aligns with the worsening cognitive dysfunction as the disease progresses.Here,we utilized in vivo PAI to analyze the changes in vascular structure during the progression of AD,elucidating the spatial and temporal correlation with cognitive impairment,which will provide more intuitive data for the study of the correlation between cerebrovascular and the development of AD.

Ensemble Forecasts of Tropical Cyclone Track with Orthogonal Conditional Nonlinear Optimal Perturbations

This paper preliminarily investigates the application of the orthogonal conditional nonlinear optimal perturbations(CNOPs)–based ensemble forecast technique in MM5(Fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model). The results show that the ensemble forecast members generated by the orthogonal CNOPs present large spreads but tend to be located on the two sides of real tropical cyclone(TC) tracks and have good agreements between ensemble spreads and ensemble-mean forecast errors for TC tracks. Subsequently, these members reflect more reasonable forecast uncertainties and enhance the orthogonal CNOPs–based ensemble-mean forecasts to obtain higher skill for TC tracks than the orthogonal SVs(singular vectors)–, BVs(bred vectors)– and RPs(random perturbations)–based ones. The results indicate that orthogonal CNOPs of smaller magnitudes should be adopted to construct the initial ensemble perturbations for short lead–time forecasts, but those of larger magnitudes should be used for longer lead–time forecasts due to the effects of nonlinearities. The performance of the orthogonal CNOPs–based ensemble-mean forecasts is case-dependent,which encourages evaluating statistically the forecast skill with more TC cases. Finally, the results show that the ensemble forecasts with only initial perturbations in this work do not increase the forecast skill of TC intensity, which may be related with both the coarse model horizontal resolution and the model error.

Possible Sources of Forecast Errors Generated by the Global/Regional Assimilation and Prediction System for Landfalling Tropical Cyclones.PartⅠ:Initial Uncertainties

This paper investigates the possible sources of errors associated with tropical cyclone （TC） tracks forecasted using the Global/Regional Assimilation and Prediction System （GRAPES）. The GRAPES forecasts were made for 16 landfaIling TCs in the western North Pacific basin during the 2008 and 2009 seasons, with a forecast length of 72 hours, and using the default initial conditions （＂initials＂, hereafter）, which are from the NCEP-FNL dataset, as well as ECMWF initials. The forecasts are compared with ECMWF forecasts. The results show that in most TCs, the GRAPES forecasts are improved when using the ECMWF initials compared with the default initials. Compared with the ECMWF initials, the default initials produce lower intensity TCs and a lower intensity subtropical high, but a higher intensity South Asia high and monsoon trough, as well as a higher temperature but lower specific humidity at the TC center. Replacement of the geopotential height and wind fields with the ECMWF initials in and around the TC center at the initial time was found to be the most efficient way to improve the forecasts. In addition, TCs that showed the greatest improvement in forecast accuracy usually had the largest initial uncertainties in TC intensity and were usually in the intensifying phase. The results demonstrate the importance of the initial intensity for TC track forecasts made using GRAPES, and indicate the model is better in describing the intensifying phase than the decaying phase of TCs. Finally, the limit of the improvement indicates that the model error associated with GRAPES forecasts may be the main cause of poor forecasts of landfalling TCs. Thus, further examinations of the model errors are required.

Possible Sources of Forecast Errors Generated by the Global/Regional Assimilation and Prediction System for Landfalling Tropical Cyclones. Part Ⅱ: Model Uncertainty

This paper investigates the possible sources of errors associated with tropical cyclone(TC) tracks forecasted using the Global/Regional Assimilation and Prediction System(GRAPES). In Part I, it is shown that the model error of GRAPES may be the main cause of poor forecasts of landfalling TCs. Thus, a further examination of the model error is the focus of Part II.Considering model error as a type of forcing, the model error can be represented by the combination of good forecasts and bad forecasts. Results show that there are systematic model errors. The model error of the geopotential height component has periodic features, with a period of 24 h and a global pattern of wavenumber 2 from west to east located between 60?S and 60?N. This periodic model error presents similar features as the atmospheric semidiurnal tide, which reflect signals from tropical diabatic heating, indicating that the parameter errors related to the tropical diabatic heating may be the source of the periodic model error. The above model errors are subtracted from the forecast equation and a series of new forecasts are made. The average forecasting capability using the rectified model is improved compared to simply improving the initial conditions of the original GRAPES model. This confirms the strong impact of the periodic model error on landfalling TC track forecasts. Besides, if the model error used to rectify the model is obtained from an examination of additional TCs, the forecasting capabilities of the corresponding rectified model will be improved.

ANTI-TUMOR RESPONSES INDUCED BY LASER IRRADIATION AND IMMUNOLOGICAL STIMULATION USING A MOUSE MAMMARY TUMOR MODEL

Anti-tunor immunological response induced by local intervention is ideal for treatment of metastatic tumors.Laser immunot herapy was developed to synergize photot hermal interaction with immunological stimulation for cancer treatment.Using an infrared laser,indocyanine green(ICG,as a light abeorbing agent),and glycated chitosan(GC,as an immunostimulant),.laser imm unot herapy has resulted in tumor suppression and anti-tumor responses in pre-clinical as well as clinical studies.To further understand the mechanism of laser immunotherapy,the efects of laser and GC treatment without specifc enhancement of laser absorption were studied.Passive adoptive immunity transfer was perfomed using splenocytes as immune cells.Spleen cells harvested from tumor-bearing mice treated by laser+GC provided 60%immunity in naive recipients.Furthermore,cytotoxicity and TNF-ar secretion by splenocytes from treated mice also indicated that laser+GC induced immunity was tumor-specific.The high level of infiltrating T cells in tumors after laser+GC treatment furt her confirned a specific anti-tumor immune response.Therefore,laser+GC could prove to be a promisi ng selective local trea tment modality that induces a systemic anti-tumor response,with appropriate laser parameters and GC doses.

Observations of intracellular second-harmonic generation imaging in black phosphorus nanosheets

Functionalized black phosphorus(BP)nanosheets have been considered as promising nanoagents in cancer therapy due to their excellent photothermal conversion efficiency.However,it is still difficult to visually monitor the dynamic localization of BP nanoagents in cancer cells.In this paper,we systematically studied the second-harmonic generation(SHG)signals originating from exfoliated BP nanosheets.Interestingly,under the excitation of a high frequency pulsed laser at 950 nm,the SHG signals of BP nanosheets in vitro are almost undetectable because of their poor stability.However,the intracellular SHG signals from BP nanosheets could be measured by in vivo optical imaging due to the efficient enrichment of living HeLa cells.Moreover,the SHG signal intensity from BP nanosheets increases with the prolonged incubation time.It can be expected that the BP nanosheets could be a promising intracellular SHG nanoprobe employed for visually in vivo biomedical imaging in practical cancer photothermal therapy(PIT).

Photonics immunotherapy-A novel strategy for cancer treatment

Photonics immunotherapy is a novel cancer treatment strategy that combines local phototherapy and immunotherapy.Phototherapy is a noninvasive or minimally invasive therapeutic strategy for local treatment of cancer,which can destroy tumor cells and release tumor antigens,inducing an in situ antitumor immune response.Immunotherapy,including the use of antibodies,vaccines,immunoadjuvants and cytokines,when combined with phototherapy,could bring a synergistic effect to stimulate a host immune response that effectuates a long-term antitumor immunity.This review will focus on the development of photonics immunotherapy and its systemic antitumor immunological effects.

Anti-tumor response induced by immunologically modified carbon nanotubes and laser irradiation using rat mammary tumor model

The ideal treatment modality for metastatic cancer would be a local treatment that can destroy primary tumors while inducing an effective systemic anti-tumor response.To this end,we de-veloped laser immunotherapy,combining photothermal laser application with an immunoadju-vant for the treatment of metastatic cancer.Additionally,to enhance the selective photothermal effect,we integrated light-absorbing nanomaterials into this innovative treatment.Specifically,we developed an immunologically modified carbon nanotube combining single-walled carbon nanotubes(SWNTs)with the immunoadjuvant glycated chitosan(GC).To determine the ef-fectiveness of laser iradiation,a series of experiments were performed using two different irra-diation durations-5 and 10 min.Rats were inoculated with DMBA-4 cancer cells,a metastatic cancer cell line.The treatment group of rats receiving laser irradiation for 10 min had a 50%long-term survival rate without residual primary or metastatic tumnors.The treatment group of rats receiving laser irradiation for 5 min had no long-term survivors;all rats died with multiple metastases at several distant sites.Therefore,Laser+SWNT-GC treatment with 10 min of laser irradiation proved to be efective at reducing tumor size and inducing long-term anti-tumor immunity.

SINGLE CELL IMAGING OF BAX TRANSLOCATION DURING APOPTOSIS INDUCED BY PHOTOFRIN-PDT

Apoptosis is an important cellular event that plays a key role in the therapy of many diseases.The mechanism of the initiation and regulation of photodynamic therapy(PDT)–induced apoptosis is complex.Our previous study found that Photofrin was localized primarily in mitochondria,the primary targets of Photofrin-PDT.The key role of Bax in the mitochondria-mediated apoptosis has been demonstrated in many systems.In order to determine the role of Bax in the mitochondrion-mediated apoptosis induced by Photofrin-PDT,we used the GFP-Bax plasmid to monitor the dynamics of Bax activation after PDT treatment.With laser scanning confocal microscopy,we found that Bax did not translocate from the cytosol to mitochondria when the mitochondrial membrane potential(∆Ψm)disappeared,measured by TMRM.Thus,for Photofrin-PDT,the commitment to cell death is independent of Bax activation.

Effects of LPLI on microglial phagocytosis in LPS-induced neuroinflammation model

Microglial activation plays an important role in neurodegenerative diseases.Once activated,they have macrophage-like capabilities,which can be beneficial by phagocytosis and harmful by se-cretion of neurotoxins.However,the resident microglia always fail to trigger an effective pha-gocytic response to clear dead cells or Aβdeposits during the progression of neurodegeneration.Therefore,the regulation of microglial phagocytosis is considered a useful strategy in searchingfor neuroprotective treatments.In this study,our results showed that low-power laser iradiation(LPLI)(20 J/cm²)could enhance microglial phagocytic function in LPS-activated microglia.Wefound that LPLI-mediated microglial phagocytosis is a Rac-1-dependent actin-based process,that a constitutively activated form of Rac1(RaclQ61L)induced a higher level of actin pol-ymerization than cells transfected with wild-type Racl,whereas a dominant negative form ofRacl(RaclT17N)markedly suppressed actin polymerization.In addition,the involvement of Racl activation after LPLI treatment was also observed by using a Raichu fluorescence resonance energy transfer(FRET)-based biosensor.We also found that PI3K/Akt pathway was required inthe LPLI-induced Raci activation.Our research may provide a feasible therapeutic approach tocontrol the progression of neurodegenerative diseases.

Interstitial photoacoustic technique and computational simulation for temperature distribution and tissue optical properties in interstitial laser photothermal interaction

Interstitial laser immunotherapy(ILIT)is designed to use photothermal and immunological inter-actions for treatment of metastatic cancers.The photothermal ffect is crucial in inducing anti-tumorimmune responses in the host.Tissue temperature and tssue optical properties are important factorsin this process.In this study,a device combining interstitial photoacoustic(PA)technique andinterstitial laser photothermal interaction is proposed.Together with computational simulation,thisdevice was designed to determine temperature distributions and tissue optical properties during lasertreatment.Experiments were performed usinger-ivoFporcine liver tissue.Our results demonstratedthat interstitial PA signal amplitude was linearly dependent on tisue temperature in the tempera-ture ranges of 20-60℃,as wll as 65-80℃,with a dfferent slope,due to the change of tissue opticalproperties.Using the directly measured temperature in the tissue around the interstitial optical fiberdiffusion tip for calibration,the theoretical temperature distribution predicted by the bioheatequation was used to extract optical properties of tssue.Finally,the three-dimensional temperature distribution was simulated to guide tumor destruction and immunological stimulation,Thus,thisnovel device and method could be used for monitoring and controlling ILIT for cancer treatment.

Advancing insights into in vivo meningeal lymphatic vessels with stereoscopic wide-field photoacoustic microscopy

Meningeal lymphatic vessels(mLVs)play a pivotal role in regulating metabolic waste from cerebrospinal fluid(CSF).However,the current limitations in field of view and resolution of existing imaging techniques impede understanding the stereoscopic morphology and dynamic behavior of mLVs in vivo.Here,we utilized dual-contrast functional photoacoustic microscopy to achieve wide-field intravital imaging of the lymphatic system,including mLVs and glymphatic pathways.The stereoscopic photoacoustic microscopy based on opto-acoustic confocal features has a depth imaging capability of 3.75 mm,facilitating differentiation between mLVs on the meninges and glymphatic pathways within the brain parenchyma.Subsequently,using this imaging technique,we were able to visualize the dynamic drainage of mLVs and identify a peak drainage period occurring around 20–40 min after injection,along with determining the flow direction from CSF to lymph nodes.Inspiringly,in the Alzheimer’s disease(AD)mouse model,we observed that AD mice exhibit a~70%reduction in drainage volume of mLVs compared to wild-type mice.With the development of AD,there is be continued decline in mLVs drainage volume.This finding clearly demonstrates that the AD mouse model has impaired CSF drainage.Our study opens up a horizon for understanding the brain’s drainage mechanism and dissecting mLVs-associated neurological disorders.

Highly efficient semiconductor modules making controllable parallel microchannels for non-compressible hemorrhages

Nature makes the most beautiful solution to involuted problems.Among them,the parallel tubular structures are capable of transporting fluid quickly in plant trunks and leaf stems,which demonstrate an ingenious evolutionary design.This study develops a mini-thermoelectric semiconductor P-N module to create gradient and parallel channeled hydrogels.The modules decrease quickly the temperature of polymer solution from 20◦C to20◦C within 5 min.In addition to the exceptional liquid absorption rate,the foams exhibited shape memory mechanics.Our mini device universally makes the inspired structure in such as chitosan,gelatin,alginate and polyvinyl alcohol.Non-compressible hemorrhages are the primary cause of death in emergency.The rapid liquid absorption leads to fast activation of coagulation,which provides an efficient strategy for hemostasis management.We demonstrated this by using our semiconductor modules on collagen-kaolin parallel channel foams with their high porosity(96.43%)and rapid expansion rate(2934%).They absorb liquid with 37.25 times of the own weight,show 46.5-fold liquid absorption speed and 24-fold of blood compared with random porous foams.These superior properties lead to strong hemostatic performance in vitro and in vivo.

A Multitime-scale Deep Learning Model for Lithium-ion Battery Health Assessment Using Soft Parameter-sharing Mechanism

Efficient assessment of battery degradation is important to effectively utilize and maintain battery management systems.This study introduces an innovative residual convolutional network(RCN)-gated recurrent unit(GRU)model to accurately assess health of lithium-ion batteries on multiple time scales.The model employs a soft parameter-sharing mechanism to identify both short-d dT and long-term degradation patterns.The continuously looped(V),T(V),dQ/dV and dT/dV are extracted to form a four-channel image,dV dV from which the RCN can automatically extract the features and the GRU can capture the temporal features.By designing a soft parameter-sharing mechanism,the model can seamlessly predict the capacity and remaining useful life(RUL)on a dual time scale.The proposed method is validated on a large MIT-Stanford dataset comprising 124 cells,showing a high accuracy in terms of mean absolute errors of 0.00477 for capacity and 83 for RUL.Furthermore,studying the partial voltage fragment reveals the promising performance of the proposed method across various voltage ranges.Specifically,in the partial voltage segment of 2.8-3.2 V,root mean square errors of 0.0107 for capacity and 140 for RUL are achieved.

Hydrophobic aerogel-modified hemostatic gauze with thermal management performance

Current hemostatic agents or dressings are not efficient under extremely hot and cold environments due to deterioration of active ingredients,water evaporation and ice crystal growth.To address these challenges,we engineered a biocompatible hemostatic system with thermoregulatory properties for harsh conditions by combining the asymmetric wetting nano-silica aerogel coated-gauze(AWNSA@G)with a layer-by-layer(LBL)structure.Our AWNSA@G was a dressing with a tunable wettability prepared by spraying the hydrophobic nano-silica aerogel onto the gauze from different distances.The hemostatic time and blood loss of the AWNSA@G were 5.1 and 6.9 times lower than normal gauze in rat’s injured femoral artery model.Moreover,the modified gauze was torn off after hemostasis without rebleeding,approximately 23.8 times of peak peeling force lower than normal gauze.For the LBL structure,consisting of the nano-silica aerogel layer and a n-octadecane phase change material layer,in both hot(70℃)and cold(-27℃)environments,exhibited dual-functional thermal management and maintained a stable internal temperature.We further verified our composite presented superior blood coagulation effect in extreme environments due to the LBL structure,the pro-coagulant properties of nano-silica aerogel and unidirectional fluid pumping of AWNSA@G.Our work,therefore,shows great hemostasis potential under normal and extreme temperature environments.

Science and Prediction of Heavy Rainfall over China:Research Progress since the Reform and Opening-Up of New China

This paper reviews the major progress on development of the science and prediction of heavy rainfall over China since the beginning of the reform and opening-up of new China(roughly between 1980 and 2019).The progress of research on the physical mechanisms of heavy rainfall over China is summarized from three perspectives:1)the relevant synoptic weather systems,2)heavy rainfall in major sub-regions of China,and 3)heavy rainfall induced by typhoons.The development and application of forecasting techniques for heavy rainfall are summarized in terms of numerical weather prediction techniques and objective forecasting methods.Greatly aided by the rapid progress in meteorological observing technology and substantial improvement in electronic computing,studies of heavy rainfall in China have advanced to investigating the evolution of heavy-rain-producing storms and observational analysis of the cloud microphysical features.A deeper and more systematic understanding of the synoptic systems of importance to the production of heavy rainfall has also been developed.Operational forecast of heavy rainfall in China has changed from subjective weather event forecasts to a combination of both subjective and objective quantitative precipitation forecasts,and is now advancing toward probabilistic quantitative precipitation forecasts with the provision of forecast uncertainty information.