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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 to −20 °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.

Abstract 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.

The cerebral lymphatic drainage plays an important role in the occurrence and development of central nervous system diseases. Recent studies have shown that cerebral lymphatic drainage is regulated by circadian rhythm and anesthesia state; however, the regulating mechanism is still unclear. In this study, we used the second near-infrared region in vivo imaging to explore the regulation of cerebral lymphatic drainage in mice at different states. At first, by injection of a tracer at different times, we confirmed that the drainage of the meningeal lymphatic system was the fastest at zeitgeber time 2, while the internal flow of the glymphatic system was the slowest. Under anesthesia with isoflurane, administration of dexmedetomidine, an anesthetic that inhibits norepinephrine (NE) release, enabled mice to enter the stage of non-rapid eye movement sleep, at which time the influx of the glymphatic system increased, the efflux of the meningeal lymphatic system decreased, and the clearance rate of the brain parenchyma decreased. However, following the exogenous NE supplement, mice quickly changed from a non-rapid eye movement stage into an awake state with the meningeal lymphatic drainage retrieval. The results showed whether the drainage of the glymphatic system and meningeal lymphatic vessels, or parenchymal clearance, has made rapid adjustments based on sleep status that is regulated by NE. This study reveals that the NE-regulated sleep–wake cycle is a powerful regulator of cerebral lymphatic drainage and provides a potential therapeutic target for related central nervous system diseases.

Abstract Meningeal lymphatic vessels (mLVs) have been shown to be involved in amyloid beta (Aβ) clearance, which is considered as a potential therapeutic target for Alzheimer’s disease (AD). In this study, based on the superficial spatial distribution of mLVs, a near-infrared light is employed to modulate lymphatic drainage, significantly improving cognition of both aged and AD (5xFAD and APP/PS1) mice, and alleviating AD-associated pathology by reducing Aβ deposition, neuroinflammation and neuronal damage. Furthermore, transmission electron microscopy imaging and RNA sequencing data indicate amelioration of mitochondrial metabolism and cellular junction of meningeal lymphatic endothelial cells (mLECs) by light modulation. These studies collectively suggest that near-infrared light treatment can improve cognitive function by strengthening scavenging ability of mLVs through restoring mLEC function. In conclusion, lymphatic drainage potentiation by light promotes pathological remission and cognitive enhancement in aging and AD mouse models, which offers a potential amelioration strategy for neurodegenerative diseases.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) can significantly extend tumor response in patients with metastatic luminal A breast cancer, yet intrinsic and acquired resistance remains a prevalent issue. Understanding the molecular features of CDK4/6 inhibitor sensitivity and the potential efficacy of their combination with novel targeted cell death inducers may lead to improved patient outcomes. Herein, we demonstrate that ferroptosis, a form of regulated cell death driven by iron-dependent phospholipid peroxidation, partly underpins the efficacy of CDK4/6 inhibitors. Mechanistically, CDK4/6 inhibitors downregulate the cystine transporter SLC7A11 by inhibiting SP1 binding to the SLC7A11 promoter region. Furthermore, SLC7A11 is identified as critical for the intrinsic sensitivity of luminal A breast cancer to CDK4/6 inhibitors. Both genetic and pharmacological inhibition of SP1 or SLC7A11 enhances cell sensitivity to CDK4/6 inhibitors and synergistically inhibits luminal A breast cancer growth when combined with CDK4/6 inhibitors in vitro and in vivo. Our data highlight the potential of targeting SLC7A11 in combination with CDK4/6 inhibitors, supporting further investigation of combination therapy in luminal A breast cancer.

Abstract At present, enzyme debridement preparation has shown a good curative effect on eschar removal of burn wounds. Keratinase has shown great potential in enzymatic debridement because of its good fibrin-degrading ability. In this study, the debridement of keratinase was examined by using a third degree burn wound model in rats. We observed the wound, and keratinase shortened the time of eschar dissolution after debridement. Histopathology and immunofluorescence staining showed that the eschar in the keratinase group became thinner, inflammatory cell infiltration in the wound increased, the fluorescence intensity of the macrophage surface marker CD68 increased, and the CD163/CD86 ratio increased. In bone marrow-derived macrophages (BMDMs), there was no significant difference in the activity of CCK-8 in cells in the keratinase group compared with the control group. The fluorescence intensity of the keratinase group was higher than that of the control group. At 12 h, the cell scratches were obviously closed. The number of migrated Transwell cells increased. Flow cytometry and immunofluorescence analysis showed increased expression of CD206 and Arg-1 and decreased expression of CD86 and iNOS. The gene expression of the Arg-1, iNOS and IL-10 was increased, as shown by qPCR. The secretion of IL-10 was increased and TNF-α was decreased, as shown by ELISA. We concluded that keratinase dissolution of eschar not only has a hydrolytic effect on eschar but may also affect immune regulation to enhance the migration and phagocytosis of macrophages, promote the polarization of macrophages, and further enhance the effect of eschar dissolution. Therefore, keratinase may have good prospects for the debridement of burn wounds.

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 °C) and cold (−27 °C) 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.

The properties of mesoporous nanomaterials have been exploited for several applications, including drug delivery and NIR-II photoacoustic imaging. Here, the authors design monodispersed semimetallic mesoporous antimony nanospheres with photothermal conversion efficiency in the second near-infrared range and drug loading capacity, showing their potential for cancer photothermal/chemo therapy.

Treatment of triple-negative breast cancer (TNBC) faces great challenges due to high invasiveness and poor prognosis. Therefore, effective treatment methods are urgently needed to control primary tumors and suppress distant tumors. Herein, we employed glycated chitosan (GC), a polysaccharide macromolecular immunoadjuvant, to construct a self-assembly GC@ICG nanoparticle which is accessible to tumor cells for synergistic cancer treatment based on the combination of phototherapy and immunotherapy. In this strategy, the self-associated synthesis of spherical GC@ICG significantly improved the stability of ICG and endowed GC with Trojan Horses in tumor cells to enhance tumor immunogenicity. A bilateral 4T1 tumor-bearing mouse model was established to evaluate the therapeutic outcomes and specific host antitumor immune response. Finally, GC@ICG-based phototherapy can directly eliminate primary tumors and resist the progression of untreated distant tumors. In addition, compared to the treatment of L + GC + ICG, GC@ICG-based phototherapy was evidenced to suppress lung metastasis and enhance infiltration of CD8+ T cells in untreated distant tumors. Therefore, this design shows promise in addressing the challenges of the treatment of TNBC.

The possible sources of forecast errors associated with rainstorms in the South China monsoon region were investigated based on Weather Research and Forecasting (WRF) model forecasts for 19 rainstorm cases that occurred in the past 13 years. Two datasets were separately selected as the initial fields of WRF with the same physical parameterization schemes. By investigating the improvement rate of the forecast when using one set of data rather than the other, the important degree of the initial conditions with respect to the forecasts for each case has been obtained. For those initial errors are the important sources of forecast errors, we further explored the source of the initial errors by comparing the two initial conditions. It was found that, interestingly, the significant differences between two initial conditions are all located upstream the rainfall area, with a distance of 5° of longitude away and an area of about 4° × 4°. Based on this, we developed a new method (which we refer to as the “guide flow method”) to identify the sensitive area for rainstorm forecasts in the South China monsoon region and then examined the efficiency of the sensitive areas. It was found that reducing the initial errors in the sensitive areas leads to better forecast results than doing the same in other areas. Thus, the sensitive areas are the source areas of forecast errors for rainstorms in the South China monsoon region.

A multiphoton absorption is one of the main nonlinear optical characteristics of semiconductor quantum dots (QDs). In this paper, we report on four-photon absorption of ZnSe:Mn QDs. The four-photon excitation spectrum is characterized under 1350 nm excitation with 50 fs femtosecond laser pulses. The experimental results indicate that the highest absorption coefficient was 2.87 × 10-5 cm5 /GW3 for Mn doping of 170 μl, and corresponding cross-section is 2.03 × 10-79 cm8·s3. We also proved that it has low biotoxicity. The results of our studies suggest that these QDs can potentially be used to detect electric fields, limit laser power, and for biosensing applications.

Photothermal therapy (PTT) has become an important therapeutic strategy in the treatment of cancer. However, exploring novel photothermal nanomaterials with satisfactory biocompatibility, high photothermal conversion efficiency, and efficient theranostic outcomes, remains a major challenge for satisfying clinical application. In this study, poly-ethylene glycol modified rhenium disulfide (PEG-ReS2) nanosheets are constructed by a simple-liquid phase exfoliation method. The PEG-ReS2 nanosheets were demonstrated to have good solubility, good biocompatibility, low toxicity, and strong capability of accumulating near-infrared (NIR) photons. Under 808 nm laser irradiation, the PEG-ReS2 nanosheets were found to have an excellent photothermal conversion efficiency (PTCE) of 42%. Moreover, the PEG-ReS2 nanosheets were demonstrated to be ideal photothermal transduction agents (PTAs), which promoted rapid cancer cell death in vitro and efficiently ablated tumors in vivo. Interestingly, the potential utility of up-regulation or down-regulation of miRNAs was proposed to evaluate the therapeutic outcomes of PEG-ReS2 nanosheets. The expression levels of a set of miRNAs in tumor-bearing mice were restored to normal levels after PTT therapy with PEG-ReS2 nanosheets. Both down-regulation miRNAs (miR-125a-5p, miR-34a-5p, miR-132-3p, and miR-148b-3p) and up-regulation miRNAs (miR-133a-3p, miR-200c-5p, miR-9-3p, and miR-150-3p) were suggested to be important clinical biomarkers for evaluating therapeutic outcomes of breast cancer-related PTT. This work highlights the great significance of PEG-ReS2 nanosheets as therapeutic nanoagents for cancer therapy.

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).

Abstract A metal‐complex‐modified graphitic carbon nitride (g‐C3N4) bulk heterostructure is presented here as a promising alternative to high‐cost noble metals as artificial photocatalysts. Theoretical and experimental studies of the spectral and physicochemical properties of three structurally similar molecules Fo–D, Pt–D, and Pt–P confirm that the Pt(II) acetylide group effectively expands the electron delocalization and adjusts the molecular orbital levels to form a relatively narrow bandgap. Using these molecules, the donor–acceptor assemblies Fo–D@CN, Pt–D@CN, and Pt–P@CN are formed with g‐C3N4. Among these assemblies, the Pt(II) acetylide‐based composite materials Pt–D@CN and Pt–P@CN with bulk heterojunction morphologies and extremely low Pt weight ratios of 0.19% and 0.24%, respectively, exhibit the fastest charge transfer and best light‐harvesting efficiencies. Among the tested assemblies, 10 mg Pt–P@CN without any Pt metal additives exhibits a significantly improved photocatalytic H2 generation rate of 1.38 µmol h−1 under simulated sunlight irradiation (AM1.5G, filter), which is sixfold higher than that of the pristine g‐C3N4.

Objective: To confirm the feasibility and accuracy of the method for evaluating blood supply and embolization rate of liver cancer based on I-flow software through animal experiments and clinical study. Methods: Rabbits underwent selective angiography under different perfusion conditions in the same kidney. The blood supply level was evaluated by I-flow software method. The results were analyzed for coefficient of variation. Thirty patients with liver cancer who underwent selective hepatic artery embolization were enrolled. The mathematical methods and 3 diagnostic specialists were used to evaluate the preoperative blood supply level and embolization rate. The results were recorded and the results were tested for consistency. Results: Animal experiments confirmed that the blood supply level analysis method designed by the research team was consistent under different contrast conditions (including total contrast agent, contrast medium perfusion rate, and limiting pressure) (coefficient of variation: 8.55%). The mathematical calculation results of preoperative blood supply level and embolization ratio of liver cancer are consistent with the average value of visual judgment results of diagnostic experts. (Preoperative blood supply level: concordance coefficient = 0.284, P = 0.003; embolization ratio: concordance coefficient = 0.218, P = 0.011). Conclusion: Based on I-flow software, the mathematical calculation method designed by this research group can effectively estimate the preoperative blood supply level of liver cancer and the embolization rate of single vascular embolization treatment, which can provide reliable data support for embolization treatment of liver cancer.

The use of carbon dots (CDs) with dual emission based on ratiometric fluorescence has been attracting attention in recent times for more accurate ion detection since they help avoid interference from background noise, probe concentration, and complexity. Herein, novel dual-emission nitrogen-doped CDs (NCDs) were prepared by a simple method for Cu2+ and ClO- detection. The NCDs showed excellent anti-interference ability and selectivity for different emissions. In addition, a good linear relationship was observed between the fluorescence intensity (FI) of the NCD solutions in different emissions with Cu2+ (0–90 μM) and ClO− (0–75 μM). The limits of both Cu2+ detection and ClO− were very low, at 17.7 and 11.6 nM, respectively. The NCDs developed herein also showed a good recovery rate in water for Cu2+ and ClO− detection. Hence, they are expected to have a more extensive application prospect in real samples.

Abstract Combined phototherapy and immunotherapy demonstrates strong potential in the treatment of metastatic cancers. An upconversion nanoparticle (UCNP) based antigen‐capturing nanoplatform is designed to synergize phototherapies and immunotherapy. In particular, this nanoplatform is constructed via self‐assembly of DSPE‐PEG‐maleimide and indocyanine green (ICG) onto UCNPs, followed by loading of the photosensitizer rose bengal (RB). ICG significantly enhances the RB‐based photodynamic therapy efficiency of UCNP/ICG/RB‐mal upon activation by a near‐infrared (NIR) laser, simultaneously achieving selective photothermal therapy. Most importantly, tumor‐derived protein antigens, arising from phototherapy‐treated tumor cells, can be captured and retained in situ, due to the functionality of maleimide, which further enhance the tumor antigen uptake and presentation by antigen‐presenting cells. The synergized photothermal, photodynamic, and immunological effects using light‐activated UCNP/ICG/RB‐mal induces a tumor‐specific immune response. In the experiments, intratumoral administration of UCNP/ICG/RB‐mal, followed by noninvasive irradiation with an NIR laser, destroys primary tumors and inhibits untreated distant tumors, using a poorly immunogenic, highly metastatic 4T1 mammary tumor model. With the simultaneous use of anti‐CTLA‐4, about 84% of the treated tumor‐bearing mice achieve long‐term survival and 34% of mice develop tumor‐specific immunity. Overall, this antigen‐capturing nanoplatform provides a promising approach for the treatment of metastatic cancers.

Previously, the research about the influence of rainfall on the discharge characteristics of the gap mainly focused on the severe non-uniform electric field gap such as rod–plane, rod–rod, or tower head of which the electrode size was generally small. As the DC voltage level increases, the size of the fitting at the end of the device further increases. As a result, the impact of rain on the discharge characteristics would have significant changes. In this study, the influence of rainwater on the electric field distribution characteristics of the sphere–plane air gap was simulated and the electric field distortion characteristic formed by the rain collected at the bottom of the fitting was obtained. Then, the impulse discharge test of the fitting under different rainfalls was conducted from which the influence of different rainfall on the impulse discharge voltage of sphere–plane gap was analysed. The research results can be used to optimise the design of the end fittings of outdoor DC field equipment.

A typhoon is an extreme weather event with strong destructive force, which can bring huge losses of life and economic damage to people. Thus, it is meaningful to reduce the prediction errors of typhoon intensity forecasting. Artificial and deep neural networks have recently become widely used for typhoon forecasting in order to ensure typhoon intensity forecasting is accurate and timely. Typhoon intensity forecasting models based on long short-term memory (LSTM) are proposed herein, which forecast typhoon intensity as a time series problem based on historical typhoon data. First, the typhoon intensity forecasting models are trained and tested with processed typhoon data from 2000 to 2014 to find the optimal prediction factors. Then, the models are validated using the optimal prediction factors compared to a feed-forward neural network (FNN). As per the results of the model applied for typhoons Chan-hom and Soudelor in 2015, the model based on LSTM using the optimal prediction factors shows the best performance and lowest prediction errors. Thus, the model based on LSTM is practical and meaningful for predicting typhoon intensity within 120 h.

Timely and accurately identification of the novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can greatly contribute to monitoring and controlling the global pandemic. This study gained theoretical insight into a novel phase-modulation plasmonic biosensor working in the near-infrared (NIR) regime, which can be employed for sensitive detection of SARS-CoV-2 and its spike (S) glycoprotein. The proposed plasmonic biosensor was created by integrating two-dimensional (2D) Van der Waals heterostructures, including tellurene and carboxyl-functionalized molybdenum disulfide (MoS _2 ) layers, with transparent indium tin oxide (ITO) film. Excellent biosensing performance can be achieved under the excitation of 1550 nm by optimizing the thickness of ITO film and tellurene-MoS _2 heterostructures. For a sensing interface refractive index change as low as 0.0012 RIU (RIU, refractive index unit), the optimized plasmonic configuration of 121 nm ITO film/three-layer tellurene/ten-layer MoS _2 -COOH can produce the highest detection sensitivity of 8.4069 × 10 ^4 degree/RIU. More importantly, MoS _2 –COOH layer can capture angiotensin-converting enzyme II, which is an ideal adsorption site for specifically binding SARS-CoV-2 S glycoprotein. Then, an excellent linear detection range for S glycoprotein and SARS-CoV-2 specimens is ∼0–301.67 nM and ∼0–67.8762 nM, respectively. This study thus offers an alternative strategy for rapidly performing novel coronavirus diagnosis in clinical applications.

Interstitial laser immunotherapy (ILIT) is designed to use photothermal and immunological interactions for treatment of metastatic cancers. The photothermal effect is crucial in inducing anti-tumor immune responses in the host. Tissue temperature and tissue optical properties are important factors in this process. In this study, a device combining interstitial photoacoustic (PA) technique and interstitial laser photothermal interaction is proposed. Together with computational simulation, this device was designed to determine temperature distributions and tissue optical properties during laser treatment. Experiments were performed using ex-vivo porcine liver tissue. Our results demonstrated that interstitial PA signal amplitude was linearly dependent on tissue temperature in the temperature ranges of 20–60∘C, as well as 65–80∘C, with a different slope, due to the change of tissue optical properties. Using the directly measured temperature in the tissue around the interstitial optical fiber diffusion tip for calibration, the theoretical temperature distribution predicted by the bioheat equation was used to extract optical properties of tissue. Finally, the three-dimensional temperature distribution was simulated to guide tumor destruction and immunological stimulation. Thus, this novel device and method could be used for monitoring and controlling ILIT for cancer treatment.

Photothermal therapy is an effective means to induce tumor cell death, since tumor tissue is more sensitive to temperature increases than normal tissue. Biological responses depend on tissue temperature; target tissue temperature needs to be precisely measured and controlled to achieve desired thermal effects. In this work, a unique photoacoustic (PA) sensor is proposed for temperature measurement during interstitial laser phototherapy. A continuous-wave laser light and a pulsed laser light, for photothermal irradiation and photoacoustic temperature measurement, respectively, were delivered to the target tissue through a fiber coupler. During laser irradiation, the PA amplitude was measured. The Grüneisen parameter and the bioheat equation were used to determine the temperature in strategic positions in the target tissue. Our results demonstrate that the interstitial PA amplitude is a linear function of temperature in the range of 22 to 55 °C, as confirmed by thermocouple measurement. Furthermore, by choosing appropriate laser parameters, the maximum temperature surrounding the active diffuse fiber tip in tissue can be controlled in the range of 41 to 55 °C. Thus, this sensor could potentially be used for fast, accurate, and convenient three-dimensional temperature measurement, and for real-time feedback and control of interstitial laser phototherapy in cancer treatment.

Fibrotic diseases, such as Dupuytren’s contracture (DC), involve excess scar tissue formation. The differentiation of fibroblasts into myofibroblasts is a significant mechanism in DC, as it generates tissue contraction in areas without wound openings, leading to the deposition of scar tissue, and eventually flexing one or more fingers in a restrictive fashion. Additionally, DC has a high recurrence rate. Previously, we showed that N-dihydrogalactochitosan (GC), an immunostimulant, inhibited myofibroblast differentiation in a DC fibroblast culture. Our goal of this study was to expand our previous study to include other DC and normal cell lines and other chitosan derivatives (GC and single-walled carbon nanotube-conjugated GC) to determine the specific mechanism of inhibition. Derivative-incorporated and vehicle control (water) anchored fibroblast-populated collagen matrices (aFPCM) were used to monitor compaction (anchored matrix height reduction) using microscopy and optical coherence tomography (OCT) for six days. Fibroblasts were unable to compact chitosan derivative aFPCM to the same extent as vehicle control aFPCM in repeated experiments. Similarly, chitosan derivative aFPCM contracted less than control aFPCM when released from anchorage. Proliferative myofibroblasts were identified by the presence of alpha smooth muscle actin via myofibroblast proliferative assay. In all tested conditions, a small percentage of myofibroblasts and proliferative cells were present. However, when aFPCM were treated with transforming growth factor-beta 1 (TGF-β1), all tested samples demonstrated increased myofibroblasts, proliferation, compaction, and contraction. Although compaction and contraction were reduced, there was sufficient tension present in the chitosan derivative aFPCM to allow exogenous stimulation of the myofibroblast phenotype.

We propose a non-linear forcing singular vector (NFSV) approach to infer the effect of non-linearity on the predictability associated with model errors. The NFSV is a generalisation of the forcing singular vector (FSV) to non-linear fields and acts as a tendency perturbation that results in a significantly large perturbation growth. In predictability studies, the NFSV, as a tendency error, may provide useful information about model errors that cause severe prediction uncertainties. In this article, a two-dimensional quasi-geostrophic (QG) model is used to study NFSVs and make a comparison between NFSVs and FSVs. We choose two basic flows: the first is a zonal steady flow (Ref-1), and the second is a meridional steady flow (Ref-2). The results demonstrate that the corresponding NFSVs contain a phase where the stream function tends to be contracted around regions of strong velocity shear. Furthermore, the NFSVs for the Ref-1 tend to have a meridional asymmetric spatial structure. Due to the absence of non-linearity, FSVs tend to have a larger spatial extension than NFSVs; in particular, the FSVs for the Ref-1 are almost symmetric in the stream function component. The prediction errors caused by FSVs in the non-linear QG model are generally smaller than those caused by FSVs in the linearised QG model; therefore, the non-linearity in the QG model would significantly saturate the perturbation growth. Nevertheless, the prediction errors caused by NFSVs (especially for the Ref-1) in the non-linear QG model are larger than those caused by FSVs, which further implies that the tendency errors of NFSV structures tend to reduce the damping effect of the non-linearity on the perturbation growth and are more applicable than those of FSV structures to describing the optimal mode of the model errors. The differences between NFSVs and FSVs demonstrate the usefulness of NFSVs in revealing the effects of non-linearity on predictability. The NFSV may be a useful non-linear technique for exploring the predictability problems introduced by model errors.

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.

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 developed laser immunotherapy, combining photothermal laser application with an immunoadjuvant 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 effectiveness of laser irradiation, a series of experiments were performed using two different irradiation 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 tumors. 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 effective at reducing tumor size and inducing long-term anti-tumor immunity.

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 secretion of neurotoxins. However, the resident microglia always fail to trigger an effective phagocytic response to clear dead cells or Aβ deposits during the progression of neurodegeneration. Therefore, the regulation of microglial phagocytosis is considered a useful strategy in searching for neuroprotective treatments. In this study, our results showed that low-power laser irradiation (LPLI) (20 J/cm2) could enhance microglial phagocytic function in LPS-activated microglia. We found that LPLI-mediated microglial phagocytosis is a Rac-1-dependent actin-based process, that a constitutively activated form of Rac1 (Rac1Q61L) induced a higher level of actin polymerization than cells transfected with wild-type Rac1, whereas a dominant negative form of Rac1 (Rac1T17N) markedly suppressed actin polymerization. In addition, the involvement of Rac1 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 in the LPLI-induced Rac1 activation. Our research may provide a feasible therapeutic approach to control the progression of neurodegenerative diseases.

Anti-tumor immunological response induced by local intervention is ideal for treatment of metastatic tumors. Laser immunotherapy was developed to synergize photothermal interaction with immunological stimulation for cancer treatment. Using an infrared laser, indocyanine green (ICG, as a light absorbing agent), and glycated chitosan (GC, as an immunostimulant), laser immunotherapy 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 effects of laser and GC treatment without specific enhancement of laser absorption were studied. Passive adoptive immunity transfer was performed 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-α secretion by splenocytes from treated mice also indicated that laser + G induced immunity was tumor-specific. The high level of infiltrating T cells in tumors after laser + GC treatment further confirmed a specific anti-tumor immune response. Therefore, laser + GC could prove to be a promising selective local treatment modality that induces a systemic anti-tumor response, with appropriate laser parameters and GC doses.