Rationally designed upconversion nanoparticles for NIR light-controlled lysosomal escape and nucleus-based photodynamic therapy.

Cell nucleus-based photodynamic therapy is a highly effective method for cancer therapy, but it is still challenging to design nucleus-targeting photosensitizers. Here, we propose the "one treatment, multiple irradiations" strategy to achieve nucleus-based photodynamic therapy using the photosensitizer rose bengal (RB)-loaded and mesoporous silica-coated upconversion nanoparticles with the surface modification of amine group (UCNP/RB@mSiO2-NH2 NPs). After implementation into cancer cells, the rationally designed UCNP/RB@mSiO2-NH2 NPs could be specifically accumulated in the acidic lysosomes due to their amino group-decorated surface. Upon a short-term (3 min) irradiation of 980 nm near-infrared light, the reactive oxygen species produced by RB through the Förster resonance energy transfer between the upconversion nanoparticles and RB molecules could effectively destroy lysosomes, followed by the release of the UCNP/RB@mSiO2-NH2 NPs from the lysosomes. Subsequently, these released UCNP/RB@mSiO2-NH2 NPs could be transferred into the cell nucleus, where a second 980 nm light irradiation was conducted to achieve the nucleus-based photodynamic therapy. The rationally designed UCNP/RB@mSiO2-NH2 NPs showed excellent anticancer performance in both two-dimensional and three-dimensional cell models using the "one treatment, multiple irradiations" strategy.

Dual Gate-Controlled Therapeutics for Overcoming Bacterium-Induced Drug Resistance and Potentiating Cancer Immunotherapy.

The presence of bacteria in the tumor can cause cancer resistance to chemotherapeutics. To fight against bacterium-induced drug resistance, herein we design self-traceable nanoreservoirs that are simultaneously loaded with gemcitabine (an anticancer drug) and ciprofloxacin (an antibiotic) and are decorated with hyaluronic acid for active tumor targeting. The nanoreservoirs have a pH-sensitive gate and an enzyme-responsive gate that can be opened in the acidic and hyaluronidase-abundant tumor microenvironment to control drug release rates. Moreover, the nanoreservoirs can specifically target the tumor regions without eliciting evident toxicity to normal tissues, kill the intratumoral bacteria, and inhibit the tumor growth even in the presence of the bacteria. Unexpectedly, the nanoreservoirs can activate T cell-mediated immune responses through promoting antigen-presenting dendritic cell maturation and depleting immunosuppressive myeloid-derived suppressor cells in bacterium-infected tumors.

Missing-Linker-Assisted Artesunate Delivery by Metal-Organic Frameworks for Synergistic Cancer Treatment.

Clinical translation of artesunate (ATS) as a potent antitumor drug has been obstructed by its rapid degradation and low bioavailability. Herein, we report the development of an ATS nanomedicine through the self-assembly with Mn[Co(CN)6 ]2/3 □1/3 metal-organic frameworks (MOFs) that have hidden missing linkers. The defects in MOFs originating from the missing linkers play a key role in increasing the biological stability and tumor accumulation of ATS. Chlorin e6 (Ce6) and ATS can be co-loaded into MOFs for a synergistic antitumor efficacy. In the presence of intracellular HCO3- , Mn2+ acts as an efficient catalyst to promote the bicarbonate-activated H2 O2 system which oxidizes ATS to generate reactive oxygen species and induce oxidative death to cancer cells. The released [CoIII (CN)6 ] linker undergoes a redox reaction with intracellular glutathione to prevent the scavenging ability of reactive oxygen species, contributing to synergistic chemodynamic therapy of ATS and photodynamic therapy of Ce6. Thus, defect-engineered MOFs with hidden missing linkers hold great promise in advancing the practical use of ATS as an antitumor medicine.

One-Step Synthesis of Epoxy Group-Terminated Organosilica Nanodots: A Versatile Nanoplatform for Imaging and Eliminating Multidrug-Resistant Bacteria and Their Biofilms.

Multidrug-resistant bacteria (MRB) and their biofilms, both of which develop high levels of drug tolerance, cause severe threats to global health. This study demonstrates that biocompatible fluorescent silicon-containing nanodots can be a multifunctional platform for simultaneously imaging and eliminating MRB and their biofilms. Ultrasmall epoxy group (oxirane)-functionalized organosilica nanodots (OSiNDs) with a high photoluminescence quantum yield of ≈31% are synthesized via a simple one-step hydrothermal treatment of an epoxy group-containing silane molecule, 3-glycidoxypropyltrimethoxysilane, and an organic dye, rose bengal. The resultant OSiNDs can be employed as a universal imaging reagent for visualizing various bacteria/biofilms, including MRB and their biofilms. Moreover, the epoxy group-terminated OSiNDs can be conjugated with amine-containing reagents only via the simple stirring of the mixtures at an elevated temperature (e.g., 60 °C) for several hours (e.g., 3 h) without the addition of activating reagents. The amine-containing antibiotic vancomycin (Van) can thus be easily conjugated with the OSiNDs, and the obtained OSiNDs-Van can successfully inhibit the growth of MRB and even eliminate their biofilms. Collectively, the present work may give new impetus to the development of novel antibacterial and anti-biofilm agents for overcoming the drug resistance of bacteria.

One-Step Synthesis of Ultrasmall and Ultrabright Organosilica Nanodots with 100% Photoluminescence Quantum Yield: Long-Term Lysosome Imaging in Living, Fixed, and Permeabilized Cells.

Water-dispersible nanomaterials with superbright photoluminescence (PL) emissions and narrow PL bandwidths are urgently desired for various imaging applications. Herein, for the first time, we prepared ultrasmall organosilica nanodots (OSiNDs) with an average size of ∼2.0 nm and ∼100% green-emitting PL quantum efficiency via a one-step hydrothermal treatment of two commercial reagents (a silane molecule and rose bengal). In particular, the structural reorganization and halide loss of rose bengal during the hydrothermal treatment contribute to the ultrahigh quantum yield and low phototoxicity of OSiNDs. Owing to their low pH-induced precipitation/aggregation property, the as-prepared OSiNDs can be used as excellent lysosomal trackers with many advantages: (1) They have superior lysosomal targeting ability with a Pearson's coefficient of 0.98; (2) The lysosomal monitoring time of OSiNDs is up to 48 h, which is much longer than those of commercial lysosomal trackers (<2 h); (3) They do not disturb the pH environment of lysosomes and can be used to visualize lysosomes in living, fixed, and permeabilized cells; (4) They exhibit intrinsic lysosomal tracking ability without the introduction of lysosome-targeting ligands (such as morpholine) and superior photostability; (5) The easy, cost-effective, and scalable synthetic method further ensures that these OSiNDs can be readily used as exceptional lysosomal trackers. We expect that the ultrasmall OSiNDs with superior fluorescence properties and easily modifiable surfaces could be applied as fluorescent nanoprobes, light-emitting diode phosphor, and anticounterfeiting material, which should be able to promote the preparation and application of silicon-containing nanomaterials.

Randomized single-blind multicenter trial comparing the effects of standard and augmented acupuncture protocols on sleep quality and depressive symptoms in patients with depression.

The study was aimed to compare the effects of standard and augmented acupuncture on depressive symptoms and sleep disturbances in patients with depression. This is a randomized, single-blind, multicenter trial. 140 subjects with clinical insomnia (score of ≥ 7 on the Pittsburgh Sleep Quality Index (PSQI)) were randomized to the standard (LI4, LIV3, EX-HN3, and GV20) or augmented (LI4, LIV3, EX-HN3, GV20, LU7, and KID6, including intradermal needles for sustained treatment) acupuncture groups. Participants received two sessions weekly for six weeks. In trial, The primary outcomes were improvements in PSQI and the Hamilton Rating Scale (HAMD). Secondary outcomes were treatment credibility and adverse events. Outcomes were assessed at baseline, week 3, end of treatment, and 4-week follow-up. From the 105 randomized patients, 89 completed the trial and were included in the final analyses. Better efficacy was observed in the augmented group compared with the standard acupuncture to improve the PSQI and HAMD at week 3, end of treatment, and 4-week follow-up (all p < .05). The HAMD scores improved with time, except between end of treatment and 4-week follow-up, while in the standard group, HAMD scored improved from baseline to week 3, and stopped improving thereafter. The PSQI scores improved with time in the two groups, except between end of treatment and 4-week follow-up. Compared with the standard protocol, the augmented acupuncture protocol had a better efficacy to treat depression and to improve sleep quality of patients with depression.

Subcellular Fate of a Fluorescent Cholesterol-Poly(ethylene glycol) Conjugate: An Excellent Plasma Membrane Imaging Reagent.

Cholesterol-containing molecules or nanoparticles play a significant role in achieving favorable plasma membrane imaging and efficient cellular uptake of drugs by the excellent membrane anchoring capability of the cholesterol moiety. By linking cholesterol to a water-soluble component (such as poly(ethylene glycol), PEG), the resulting cholesterol-PEG conjugate can form micelles in aqueous solution through self-assembly, and such a micellar structure represents an important drug delivery vehicle in which hydrophobic drugs can be encapsulated. However, the understanding of the subcellular fate and cytotoxicity of cholesterol-PEG conjugates themselves remains elusive. Herein, by using cholesterol-PEG2000-fluorescein isothiocyanate (Chol-PEG-FITC) as a model system, we found that the Chol-PEG-FITC molecules could attach to the plasma membranes of mammalian cells within 10 min and such a firm membrane attachment could last at least 1 h, displaying excellent plasma membrane staining performance that surpassed that of commonly used commercial membrane dyes such as DiD and CellMask. Besides, we systematically studied the endocytosis pathway and intracellular distribution of Chol-PEG-FITC and found that the cell surface adsorption and endocytosis processes of Chol-PEG-FITC molecules were lipid-raft-dependent. After internalization, the Chol-PEG-FITC molecules gradually reached many organelles with membrane structures. At 5 h, they were mainly distributed in lysosomes and the Golgi apparatus, with some in the endoplasmic reticulum (ER) and very few in the mitochondrion. At 12 h, the Chol-PEG-FITC molecules mostly aggregated in the Golgi apparatus and ER close to the nucleus. Finally, we demonstrated that Chol-PEG-FITC was toxic to mammalian cells only at concentrations above 50 µM. In summary, Chol-PEG-FITC can be a promising plasma membrane imaging reagent to avoid the fast cellular internalization and quick membrane detachment problems faced by commercial membrane dyes. We believe that the investigation of the dynamic subcellular fate of Chol-PEG-FITC can provide important knowledge to facilitate the use of cholesterol-PEG conjugates in fields such as cell surface engineering and drug delivery.

Highly sensitive and selective detection of dopamine using one-pot synthesized highly photoluminescent silicon nanoparticles.

A simple and highly efficient method for dopamine (DA) detection using water-soluble silicon nanoparticles (SiNPs) was reported. The SiNPs with a high quantum yield of 23.6% were synthesized by using a one-pot microwave-assisted method. The fluorescence quenching capability of a variety of molecules on the synthesized SiNPs has been tested; only DA molecules were found to be able to quench the fluorescence of these SiNPs effectively. Therefore, such a quenching effect can be used to selectively detect DA. All other molecules tested have little interference with the dopamine detection, including ascorbic acid, which commonly exists in cells and can possibly affect the dopamine detection. The ratio of the fluorescence intensity difference between the quenched and unquenched cases versus the fluorescence intensity without quenching (ΔI/I) was observed to be linearly proportional to the DA analyte concentration in the range from 0.005 to 10.0 µM, with a detection limit of 0.3 nM (S/N = 3). To the best of our knowledge, this is the lowest limit for DA detection reported so far. The mechanism of fluorescence quenching is attributed to the energy transfer from the SiNPs to the oxidized dopamine molecules through Förster resonance energy transfer. The reported method of SiNP synthesis is very simple and cheap, making the above sensitive and selective DA detection approach using SiNPs practical for many applications.

[Chemical components from essential oil of Pandanus amaryllifolius leaves].

OBJECTIVE: To analyze the chemical compositions of Pandanus amaryllifolius leaves essential oil extracted by steam distillation. METHODS: The essential oil of Pandanus amaryllifolius leaves was analyzed by gas chromatography-mass spectrum, and the relative content of each component was determined by area normalization method. RESULTS: 128 peaks were separated and 95 compounds were identified, which weighed 97.75%. The main chemical components of the essential oil were phytol (42.15%), squalene (16.81%), what's more pentadecanal (6.17%), pentadecanoic acid (4.49%), 3, 7, 11, 15-tetramethyl-2-hexadecen-1-ol (3.83%), phytone (2.05%) and the other 74 chemical compositions were firstly identified from the essential oil of Pandanus amaryllifolius leaves. CONCLUSION: The chemical compositions of Pandanu samaryllifolius leaves essential oil was systematically, deeply isolated and identified for the first time. This experiment has provided scientific foundation for further utilization of Pandanus amaryllifolius leaves.

Metal-Organic Framework-Based Nanovaccine for Relieving Immunosuppressive Tumors via Hindering Efferocytosis of Macrophages and Promoting Pyroptosis and Cuproptosis of Cancer Cells.

Current cancer vaccines face challenges due to an immunosuppressive tumor microenvironment and their limited ability to produce an effective immune response. To address the above limitations, we develop a 3-(2-spiroadamantyl)-4-methoxy-4-(3-phosphoryloxy)-phenyl-1,2-dioxetane (alkaline phosphatase substrate) and XMD8-92 (extracellular signal-regulated kinase 5 inhibitor)-codelivered copper-tetrahydroxybenzoquinone (Cu-THBQ/AX) nanosized metal-organic framework to in situ-generate therapeutic vaccination. Once inside the early endosome, the alkaline phosphatase overexpressed in the tumor cells' membrane activates the in situ type I photodynamic effect of Cu-THBQ/AX for generating •O2-, and the Cu-THBQ/AX catalyzes O2 and H2O2 to •O2- and •OH via semiquinone radical catalysis and Fenton-like reactions. This surge of ROS in early endosomes triggers caspase-3-mediated proinflammatory pyroptosis via activating phospholipase C. Meanwhile, Cu-THBQ/AX can also induce the oligomerization of dihydrolipoamide S-acetyltransferase to trigger tumor cell cuproptosis. The production of •OH could also trigger the release of XMD8-92 for effectively inhibiting the efferocytosis of macrophages to convert immunosuppressive apoptosis of cancer cells into proinflammatory secondary necrosis. The simultaneous induction of pyroptosis, cuproptosis, and secondary necrosis effectively converts the tumor microenvironment from "cold" to "hot" conditions, making it an effective antigen pool. This transformation successfully activates the antitumor immune response, inhibiting tumor growth and metastasis.

A red blood cell-derived bionic microrobot capable of hierarchically adapting to five critical stages in systemic drug delivery.

The tumour-targeting efficiency of systemically delivered chemodrugs largely dictates the therapeutic outcome of anticancer treatment. Major challenges lie in the complexity of diverse biological barriers that drug delivery systems must hierarchically overcome to reach their cellular/subcellular targets. Herein, an "all-in-one" red blood cell (RBC)-derived microrobot that can hierarchically adapt to five critical stages during systemic drug delivery, that is, circulation, accumulation, release, extravasation, and penetration, is developed. The microrobots behave like natural RBCs in blood circulation, due to their almost identical surface properties, but can be magnetically manipulated to accumulate at regions of interest such as tumours. Next, the microrobots are "immolated" under laser irradiation to release their therapeutic cargoes and, by generating heat, to enhance drug extravasation through vascular barriers. As a coloaded agent, pirfenidone (PFD) can inhibit the formation of extracellular matrix and increase the penetration depth of chemodrugs in the solid tumour. It is demonstrated that this system effectively suppresses both primary and metastatic tumours in mouse models without evident side effects, and may represent a new class of intelligent biomimicking robots for biomedical applications.

Epidemiology and clinical presentation of the four human parainfluenza virus types.

BACKGROUND: Human parainfluenza viruses (HPIVs) are important causes of upper respiratory tract illness (URTI) and lower respiratory tract illness (LRTI). To analyse epidemiologic and clinical characteristics of the four types of human parainfluenza viruses (HPIVs), patients with acute respiratory tract illness (ARTI) were studied in Guangzhou, southern China. METHODS: Throat swabs (n=4755) were collected and tested from children and adults with ARTI over a 26-month period, and 4447 of 4755 (93.5%) patients' clinical presentations were recorded for further analysis. RESULTS: Of 4755 patients tested, 178 (3.7%) were positive for HPIV. Ninety-nine (2.1%) samples were positive for HPIV-3, 58 (1.2%) for HPIV-1, 19 (0.4%) for HPIV-2 and 8 (0.2%) for HPIV-4. 160/178 (88.9%) HPIV-positive samples were from paediatric patients younger than 5 years old, but no infant under one month of age was HPIV positive. Seasonal peaks of HPIV-3 and HPIV-1 occurred as autumn turned to winter and summer turned to autumn. HPIV-2 and HPIV-4 were detected less frequently, and their frequency of isolation increased when the frequency of HPIV-3 and HPIV-1 declined. HPIV infection led to a wide spectrum of symptoms, and more "hoarseness" (p=0.015), "abnormal pulmonary breathing sound" (p<0.001), "dyspnoea" (p<0.001), "pneumonia" (p=0.01), and "diarrhoea" (p<0.001) presented in HPIV-positive patients than HPIV-negative patients. 10/10 (100%) HPIV-positive adult patients (≥14 years old) presented with systemic influenza-like symptoms, while 90/164 (54.9%) HPIV-positive paediatric patients (<14 years old) presented with these symptoms (p=0.005). The only significant difference in clinical presentation between HPIV types was "Expectoration" (p<0.001). Co-infections were common, with 33.3%-63.2% of samples positive for the four HPIV types also testing positive for other respiratory pathogens. However, no significant differences were seen in clinical presentation between patients solely infected with HPIV and patients co-infected with HPIV and other respiratory pathogens. CONCLUSIONS: HPIV infection led to a wide spectrum of symptoms, and similar clinical manifestations were found in the patients with four different types of HPIVs. The study suggested pathogenic activity of HPIV in gastrointestinal illness. The clinical presentation of HPIV infection may differ by patient age.

Influence of age and HBeAg status on the correlation between HBV DNA and hepatic inflammation and fibrosis in chronic hepatitis B patients.

AIMS: The purpose of this study was to examine the correlation between serum HBV DNA level and the severity of hepatic inflammation and fibrosis in patients with chronic hepatitis B. METHODS: Liver function, serological markers of HBV and serum HBV DNA quantification were assayed in 215 CHB patients who also underwent liver biopsy. Liver pathology was regarded as the evaluation criteria to evaluate the correlation between serum HBV DNA level and the severity of liver inflammation and fibrosis. RESULTS: Of the 215 patients, 136 were HBeAg-positive and 79 were HBeAg-negative; 134 patients had mild hepatic inflammation and fibrosis and 81 had significant hepatic inflammation and fibrosis in pathological diagnosis. We found that positive correlation between the severity of hepatic inflammation and fibrosis and serum HBV DNA level was only present in HBeAg-negative patients but not HBeAg-positive patients (P < 0.001). Patients' age was a key factor influencing the correlation between serum HBV DNA level and the severity of hepatic inflammation and fibrosis. the cutoff values to predict the severity of hepatic inflammation and fibrosis were 33.5 and 36 years, respectively. Using 35 years as the cutoff value, positive correlation between serum HBV DNA level and hepatic inflammation and fibrosis was observed in both HBeAg-positive and HBeAg-negative patients aged ≥ 35 years (P < 0.05), however no correlation was observed in HBeAg-positive patients aged <35 years. CONCLUSIONS: There was positive correlation between serum HBV DNA level and hepatic inflammation and fibrosis in both HBeAg-positive and HBeAg-negative patients' aged ≥ 35 years, but in patients aged <35 years, positive correlation was only observed in HBeAg-negative patients.

Nanocompartment-confined polymerization in living systems.

Polymerization in living systems has become an effective strategy to regulate cell functions and behavior. However, the requirement of high concentrations of monomers, the existence of complicated intracorporal interferences, and the demand for extra external stimulations hinder their further biological applications. Herein, a nanocompartment-confined strategy that provides a confined and secluded environment for monomer enrichment and isolation is developed to achieve high polymerization efficiency, reduce the interference from external environment, and realize broad-spectrum polymerizations in living systems. For exogenous photopolymerization, the light-mediated free-radical polymerization of sodium 4-styrenesulfonate induces a 2.7-fold increase in the reaction rate with the protection of a confined environment. For endogenous hydrogen peroxide-responsive polymerization, p­aminodiphenylamine hydrochloride embedded in a nanocompartment not only performs a 6.4-fold higher reaction rate than that of free monomers, but also activates an effective second near-infrared photoacoustic imaging-guided photothermal immunotherapy at tumor sites. This nanocompartment-confined strategy breaks the shackles of conventional polymerization, providing a universal platform for in vivo synthesis of polymers with diverse structures and functions.

Cooperative supramolecular polymerization of styrylpyrenes for color-dependent circularly polarized luminescence and photocycloaddition.

Developing facile and efficient methods to obtain circularly polarized luminescence (CPL) materials with a large luminescence dissymmetry factor (glum) and fluorescence quantum yield (ΦY) is attractive but still challenging. Herein, supramolecular polymerization of styrylpyrenes (R/S-PEB) is utilized to attain this aim, which can self-assemble into helical nanoribbons. Benefiting from the dominant CH-π interactions between the chromophores, the supramolecular solution of S-PEB shows remarkable blue-color CPL property (glum: 0.011, ΦY: 69%). From supramolecular solution to gel, the emission color (blue to yellow-green) and handedness of CPL (glum: -0.011 to +0.005) are concurrently manipulated, while the corresponding supramolecular chirality maintains unchanged, representing the rare example of color-dependent CPL materials. Thanks to the supramolecular confine effect, the [2 + 2] cycloaddition reaction rate of the supramolecular solution is 10.5 times higher than that of the monomeric solution. In contrast, no cycloaddition reaction occurs for the gel and assembled solid samples. Our findings provide a vision for fabricating multi-modal and high-performance CPL-active materials, paving the way for the development of advanced photo-responsive chiral systems.

Cucurbit[8]uril-based water-dispersible assemblies with enhanced optoacoustic performance for multispectral optoacoustic imaging.

Organic small-molecule contrast agents have attracted considerable attention in the field of multispectral optoacoustic imaging, but their weak optoacoustic performance resulted from relatively low extinction coefficient and poor water solubility restrains their widespread applications. Herein, we address these limitations by constructing supramolecular assemblies based on cucurbit[8]uril (CB[8]). Two dixanthene-based chromophores (DXP and DXBTZ) are synthesized as the model guest compounds, and then included in CB[8] to prepare host-guest complexes. The obtained DXP-CB[8] and DXBTZ-CB[8] display red-shifted and increased absorption as well as decreased fluorescence, thereby leading to a substantial enhancement in optoacoustic performance. Biological application potential of DXBTZ-CB[8] is investigated after co-assembly with chondroitin sulfate A (CSA). Benefiting from the excellent optoacoustic property of DXBTZ-CB[8] and the CD44-targeting feature of CSA, the formulated DXBTZ-CB[8]/CSA can effectively detect and diagnose subcutaneous tumors, orthotopic bladder tumors, lymphatic metastasis of tumors and ischemia/reperfusion-induced acute kidney injury in mouse models with multispectral optoacoustic imaging.

Microbial synthesis of Prussian blue for potentiating checkpoint blockade immunotherapy.

Cancer immunotherapy is revolutionizing oncology. The marriage of nanotechnology and immunotherapy offers a great opportunity to amplify antitumor immune response in a safe and effective manner. Here, electrochemically active Shewanella oneidensis MR-1 can be applied to produce FDA-approved Prussian blue nanoparticles on a large-scale. We present a mitochondria-targeting nanoplatform, MiBaMc, which consists of Prussian blue decorated bacteria membrane fragments having further modifications with chlorin e6 and triphenylphosphine. We find that MiBaMc specifically targets mitochondria and induces amplified photo-damages and immunogenic cell death of tumor cells under light irradiation. The released tumor antigens subsequently promote the maturation of dendritic cells in tumor-draining lymph nodes, eliciting T cell-mediated immune response. In two tumor-bearing mouse models using female mice, MiBaMc triggered phototherapy synergizes with anti-PDL1 blocking antibody for enhanced tumor inhibition. Collectively, the present study demonstrates biological precipitation synthetic strategy of targeted nanoparticles holds great potential for the preparation of microbial membrane-based nanoplatforms to boost antitumor immunity.

The effect of sulindac, a non-steroidal anti-inflammatory drug, attenuates inflammation and fibrosis in a mouse model of chronic pancreatitis.

BACKGROUND: Chronic pancreatitis is characterized by progressive fibrosis, pain and loss of exocrine and endocrine functions. The long-standing chronic pancreatitis and its associated pancreatic fibrosis are the most common pathogenic events involved in human pancreatic carcinogenesis, but the therapeutic strategies to chronic pancreatitis and the chemoprevention of pancreatic carcinogenesis are very limited. METHODS: We investigated the effect of sulindac, a non-steroidal anti-inflammatory drug (NSAID), on inhibition of chronic pancreatitis in a caerulein induced chronic pancreatitis mouse model. RESULTS: Sulindac significantly reduced the severity of chronic pancreatitis including the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The protein expression of phosphorylation of MEK/ERK was inhibited in the chronic pancreatic tissues by sulindac treatment as measured by Western blot assay. The levels of inflammatory cytokines including TNF-α and MCP-1 were also significantly decreased with sulindac treatment, as well as the expression of TGF-ß, PDGF-ß, SHH and Gli in the chronic pancreatic tissue detected by qPCR assay and confirmed by western blot assay. The activation of pancreatic satellet cells was also inhibited by sulindac as measured by the activity of α-smooth muscle actin (α-SMA) in the pancreatic tissue of chronic pancreatitis. CONCLUSIONS: Sulindac is a promising reagent for the treatment of chronic pancreatitis via inhibition of inflammatory cell infiltration and stromal fibrosis, the inhibitory effect of sulindac on chronic pancreatitis may through targeting the activation ERK/MAPK signaling pathway.

Nanozymes: Versatile Platforms for Cancer Diagnosis and Therapy.

Natural enzymes usually suffer from high production cost, ease of denaturation and inactivation, and low yield, making them difficult to be broadly applicable. As an emerging type of artificial enzyme, nanozymes that combine the characteristics of nanomaterials and enzymes are promising alternatives. On the one hand, nanozymes have high enzyme-like catalytic activities to regulate biochemical reactions. On the other hand, nanozymes also inherit the properties of nanomaterials, which can ameliorate the shortcomings of natural enzymes and serve as versatile platforms for diverse applications. In this review, various nanozymes that mimic the catalytic activity of different enzymes are introduced. The achievements of nanozymes in different cancer diagnosis and treatment technologies are summarized by highlighting the advantages of nanozymes in these applications. Finally, future research directions in this rapidly developing field are outlooked.

The clinical effects of brain-computer interface with robot on upper-limb function for post-stroke rehabilitation: a meta-analysis and systematic review.

PURPOSE: Many recent clinical studies have suggested that the combination of brain-computer interfaces (BCIs) can induce neurological recovery and improvement in motor function. In this review, we performed a systematic review and meta-analysis to evaluate the clinical effects of BCI-robot systems. METHODS: The articles published from January 2010 to December 2020 have been searched by using the databases (EMBASE, PubMed, CINAHL, EBSCO, Web of Science and manual search). The single-group studies were qualitatively described, and only the controlled-trial studies were included for the meta-analysis. The mean difference (MD) of Fugl-Meyer Assessment (FMA) scores were pooled and the random-effects model method was used to perform the meta-analysis. The PRISMA criteria were followed in current review. RESULTS: A total of 897 records were identified, eight single-group studies and 11 controlled-trial studies were included in our review. The systematic analysis indicated that the BCI-robot systems had a significant improvement on motor function recovery. The meta-analysis showed there were no statistic differences between BCI-robot groups and robot groups, neither in the immediate effects nor long-term effects (p > 0.05). CONCLUSION: The use of BCI-robot systems has significant improvement on the motor function recovery of hemiparetic upper-limb, and there is a sustaining effect. The meta-analysis showed no statistical difference between the experimental group (BCI-robot) and the control group (robot). However, there are a few shortcomings in the experimental design of existing studies, more clinical trials need to be conducted, and the experimental design needs to be more rigorous.Implications for RehabilitationIn this review, we evaluated the clinical effects of brain-computer interface with robot on upper-limb function for post-stroke rehabilitation. After we screened the databases, 19 articles were included in this review. These articles all clinical trial research, they all used non-invasive brain-computer interfaces and upper-limb robot.We conducted the systematic review with nine articles, the result indicated that the BCI-robot system had a significant improvement on motor function recovery. Eleven articles were included for the meta-analysis, the result showed there were no statistic differences between BCI-robot groups and robot groups, neither in the immediate effects nor long-term effects.We thought the result of meta-analysis which showed no statistic difference was probably caused by the heterogenicity of clinical trial designs of these articles.We thought the BCI-robot systems are promising strategies for post-stroke rehabilitation. And we gave several suggestions for further research: (1) The experimental design should be more rigorous, and describe the experimental designs in detail, especially the control group intervention, to make the experiment replicability. (2) New evaluation criteria need to be established, more objective assessment such as biomechanical assessment, fMRI should be utilised as the primary outcome. (3) More clinical studies with larger sample size, novel external devices, and BCI systems need to be conducted to investigate the differences between BCI-robot system and other interventions. (4) Further research could shift the focus to the patients who are in subacute stage, to explore if the early BCI training can make a positive impact on cerebral cortical recovery.