Synthesis of organic-inorganic hybrid nanocomposites modified by catalase-like catalytic sites for the controlling of kiwifruit bacterial canker.

Kiwifruit bacterial canker, caused by Pseudomonas syringae pv. Actinidiae (Psa), is one of the most important diseases in kiwifruit, creating huge economic losses to kiwifruit-growing countries around the world. Metal-based nanomaterials offer a promising alternative strategy to combat plant diseases induced by bacterial infection. However, it is still challenging to design highly active nanomaterials for controlling kiwifruit bacterial canker. Here, a novel multifunctional nanocomposite (ZnO@PDA-Mn) is designed that integrates the antibacterial activity of zinc oxide nanoparticles (ZnO NPs) with the plant reactive oxygen species scavenging ability of catalase (CAT) enzyme-like active sites through introducing manganese modified polydopamine (PDA) coating. The results reveal that ZnO@PDA-Mn nanocomposites can efficiently catalyze the conversion of H2O2 to O2 and H2O to achieve excellent CAT-like activity. In vitro experiments demonstrate that ZnO@PDA-Mn nanocomposites maintain the antibacterial activity of ZnO NPs and induce significant damage to bacterial cell membranes. Importantly, ZnO@PDA-Mn nanocomposites display outstanding curative and protective efficiencies of 47.7% and 53.8% at a dose of 200 µg mL-1 against Psa in vivo, which are superior to those of zinc thiozole (20.6% and 8.8%) and ZnO (38.7% and 33.8%). The nanocomposites offer improved in vivo control efficacy through direct bactericidal effects and decreasing oxidative damage in plants induced by bacterial infection. Our research underscores the potential of nanocomposites containing CAT-like active sites in plant protection, offering a promising strategy for sustainable disease management in agriculture.

Multifunctional Fluoropolymer-Engineered Magnetic Nanoparticles to Facilitate Blood-Brain Barrier Penetration and Effective Gene Silencing in Medulloblastoma.

Patients with brain cancers including medulloblastoma lack treatments that are effective long-term and without side effects. In this study, a multifunctional fluoropolymer-engineered iron oxide nanoparticle gene-therapeutic platform is presented to overcome these challenges. The fluoropolymers are designed and synthesized to incorporate various properties including robust anchoring moieties for efficient surface coating, cationic components to facilitate short interference RNA (siRNA) binding, and a fluorinated tail to ensure stability in serum. The blood-brain barrier (BBB) tailored system demonstrates enhanced BBB penetration, facilitates delivery of functionally active siRNA to medulloblastoma cells, and delivers a significant, almost complete block in protein expression within an in vitro extracellular acidic environment (pH 6.7) - as favored by most cancer cells. In vivo, it effectively crosses an intact BBB, provides contrast for magnetic resonance imaging (MRI), and delivers siRNA capable of slowing tumor growth without causing signs of toxicity - meaning it possesses a safe theranostic function. The pioneering methodology applied shows significant promise in the advancement of brain and tumor microenvironment-focused MRI-siRNA theranostics for the better treatment and diagnosis of medulloblastoma.

Beyond the ß-amino alcohols framework: identification of novel ß-hydroxy pyridinium salt-decorated pterostilbene derivatives as bacterial virulence factor inhibitors.

BACKGROUND: Bacterial virulence factors are involved in various biological processes and mediate persistent bacterial infections. Focusing on virulence factors of phytopathogenic bacteria is an attractive strategy and crucial direction in pesticide discovery to prevent invasive and persistent bacterial infection. Hence, discovery and development of novel agrochemicals with high activity, low-risk, and potent anti-virulence is urgently needed to control plant bacterial diseases. RESULTS: A series of novel ß-hydroxy pyridinium cation decorated pterostilbene derivatives were prepared and their antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) were systematacially assessed. Among these pterostilbene derivatives, compound 4S exhibited the best antibacterial activity against Xoo in vitro, with an half maximal effective concentration (EC50) value of 0.28 µg mL-1. A series of biochemical assays including scanning electron microscopy, crystal violet staining, and analysis of biofilm formation, swimming motility, and related virulence factor gene expression levels demonstrated that compound 4S could function as a new anti-virulence factor inhibitor by interfering with the bacterial infection process. Furthermore, the pot experiments provided convinced evidence that compound 4S had the high control efficacy (curative activity: 71.4%, protective activity: 72.6%), and could be used to effectively manage rice bacterial leaf blight in vivo. CONCLUSION: Compounds 4S is an attractive virulence factor inhibitor with potential for application in treating plant bacterial diseases by suppressing production of several virulence factors. © 2024 Society of Chemical Industry.

Selective Formation of Homochiral Dimers by Intermolecular Charge Transfer on a hBN Nanomesh.

In this study, a comprehensive characterization was conducted on a chiral starburst molecule (C57H48N4, SBM) using scanning tunneling microscopy. When adsorbed onto the hBN/Rh(111) nanomesh, these molecules demonstrate homochiral recognition, leading to a selective formation of homochiral dimers. Further tip manipulation experiments reveal that the chiral dimers are stable and primarily controlled by strong intermolecular interactions. Density functional theory (DFT) calculations supported that the chiral recognition of SBM molecules is governed by the intermolecular charge transfer mechanism, different from the common steric hindrance effect. This study emphasizes the importance of intermolecular charge transfer interactions, offering valuable insights into the chiral recognition of a simple bimolecular system. These findings hold significance for the future advancement in chirality-based electronic sensors and pharmaceuticals, where the chirality of molecules can impact their properties.

Tbl1 promotes Wnt-ß-catenin signaling-induced degradation of the Tcf7l1 protein in mouse embryonic stem cells.

Activation of the Wnt-ß-catenin signaling pathway by CHIR99021, a specific inhibitor of GSK3ß, induces Tcf7l1 protein degradation, which facilitates the maintenance of an undifferentiated state in mouse embryonic stem cells (mESCs); however, the precise mechanism is still unclear. Here, we showed that the overexpression of transducin-ß-like protein 1 (Tbl1, also known as Tbl1x) or its family member Tblr1 (also known as Tbl1xr1) can decrease Tcf7l1 protein levels, whereas knockdown of each gene increases Tcf7l1 levels without affecting Tcf7l1 transcription. Interestingly, only Tbl1, and not Tblr1, interacts with Tcf7l1. Mechanistically, Tbl1 translocates from the cytoplasm into the nucleus in association with ß-catenin (CTNNB1) after the addition of CHIR99021 and functions as an adaptor to promote ubiquitylation of the Tcf7l1 protein. Functional assays further revealed that enforced expression of Tbl1 is capable of delaying mESC differentiation. In contrast, knockdown of Tbl1 attenuates the effect of CHIR99021 on Tcf7l1 protein stability and mESC self-renewal. Our results provide insight into the regulatory network of the Wnt-ß-catenin signaling pathway involved in promoting the maintenance of naïve pluripotency.

Evaluation of AlphaFold2 Structures for Hit Identification across Multiple Scenarios.

The introduction of AlphaFold2 (AF2) has sparked significant enthusiasm and generated extensive discussion within the scientific community, particularly among drug discovery researchers. Although previous studies have addressed the performance of AF2 structures in virtual screening (VS), a more comprehensive investigation is still necessary considering the paramount importance of structural accuracy in drug design. In this study, we evaluate the performance of AF2 structures in VS across three common drug discovery scenarios: targets with holo, apo, and AF2 structures; targets with only apo and AF2 structures; and targets exclusively with AF2 structures. We utilized both the traditional physics-based Glide and the deep-learning-based scoring function RTMscore to rank the compounds in the DUD-E, DEKOIS 2.0, and DECOY data sets. The results demonstrate that, overall, the performance of VS on AF2 structures is comparable to that on apo structures but notably inferior to that on holo structures across diverse scenarios. Moreover, when a target has solely AF2 structure, selecting the holo structure of the target from different subtypes within the same protein family produces comparable results with the AF2 structure for VS on the data set of the AF2 structures, and significantly better results than the AF2 structures on its own data set. This indicates that utilizing AF2 structures for docking-based VS may not yield most satisfactory outcomes, even when solely AF2 structures are available. Moreover, we rule out the possibility that the variations in VS performance between the binding pockets of AF2 and holo structures arise from the differences in their biological assembly composition.

Recent progress and outlooks in rhodamine-based fluorescent probes for detection and imaging of reactive oxygen, nitrogen, and sulfur species.

Reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) serve as vital mediators essential for preserving intracellular redox homeostasis within the human body, thereby possessing significant implications across physiological and pathological domains. Nevertheless, deviations from normal levels of ROS, RNS, and RSS disturb redox homeostasis, leading to detrimental consequences that compromise bodily integrity. This disruption is closely linked to the onset of various human diseases, thereby posing a substantial threat to human health and survival. Small-molecule fluorescent probes exhibit considerable potential as analytical instruments for the monitoring of ROS, RNS, and RSS due to their exceptional sensitivity and selectivity, operational simplicity, non-invasiveness, localization capabilities, and ability to facilitate in situ optical signal generation for real-time dynamic analyte monitoring. Due to their distinctive transition from their spirocyclic form (non-fluorescent) to their ring-opened form (fluorescent), along with their exceptional light stability, broad wavelength range, high fluorescence quantum yield, and high extinction coefficient, rhodamine fluorophores have been extensively employed in the development of fluorescent probes. This review primarily concentrates on the investigation of fluorescent probes utilizing rhodamine dyes for ROS, RNS, and RSS detection from the perspective of different response groups since 2016. The scope of this review encompasses the design of probe structures, elucidation of response mechanisms, and exploration of biological applications.

Establishment of a multi-strategy platform for quality control and quality markers screen of Mailuoshutong pill.

Thromboangiitis obliterans (TAO) is a non-atherosclerotic segmental inflammatory occlusive disease with a high recurrence rate, high disability rate, difficulty to cure, and poor prognosis. It has been clinically proven that Mailuoshutong pill (MLSTP) is an effective traditional Chinese medicine for treating TAO. As MLSTP contains hundreds of chemical components, the quality control of which is a challenge in the development of reliable quality evaluation metrics. This study aimed to evaluate the quality uniformity of MLSTP by establishing a multi-strategy platform. In the present study, the key targets and signaling pathways of MLSTP treating TAO were predicted by network pharmacology. It was further shown by in vivo validation experiments that MLSTP exerted therapeutic effects on TAO by modulating the PI3K-AKT signaling pathway, VEGF signaling pathway, and HIF-1 signaling pathway. In addition, UPLC fingerprints of MLSTP were established and screened for potential Q-markers of MLSTP in combination with network pharmacology results. Six components, including chlorogenic acid, liquiritin, paeoniflorin, calycosin-7-glucoside, berberine, and formononetin, were selected as potential quality markers (Q-markers) in MLSTP. Finally, the quantitative analysis of multi-components by single marker (QAMS) method was established to quantitatively analyze the six potential Q-markers, and the results were consistent with those obtained by the external standard method (ESM). Taken together, the multi-strategy platform established in this study would be conducive to the Q-markers screening and quality control of MLSTP, improving the quality standard of MLSTP and providing favorable assurance for the clinical management of TAO.

An integrative platform for detection of RNA 2'-O-methylation reveals its broad distribution on mRNA.

Ribose 2'-O-methylation is involved in critical biological processes, but its biological functions and significance in mRNAs remain underexplored. We have developed NJU-seq, a sensitive method for unbiased 2'-O-methylation (Nm) profiling, and Nm-VAQ, a site-specific quantification tool. Using these tools in tandem, we identified thousands of Nm sites on mRNAs of human and mouse cell lines, of which 68 of 84 selected sites were further validated to be more than 1% 2'-O-methylated. Unlike rRNA, most mRNA Nm sites were from 1% to 30% methylated. In addition, mRNA Nm was dynamic, changing according to the circumstance. Furthermore, we show that fibrillarin is involved as a methyltransferase. By mimicking the detected Nm sites and the context sequence, the RNA fragments could be 2'-O-methylated and demonstrated higher stability but lower translation efficiency. Last, profiling of Nm sites in lung surgery samples revealed common signatures of lung cancer pathogenesis, providing potential new diagnostic markers.

Identification of Novel Bisamide-Decorated Benzotriazole Derivatives as Anti-Phytopathogenic Virus Agents: Bioactivity Evaluation and Computational Simulation.

As a notorious phytopathogenic virus, the tobacco mosaic virus (TMV) severely reduced the quality of crops worldwide and caused critical constraints on agricultural production. The development of novel virucides is a persuasive strategy to address this predicament. Herein, a series of novel bisamide-decorated benzotriazole derivatives were elaborately prepared and screened. Biological tests implied that the optimized compound 7d possessed the most brilliant antiviral inactive profile (EC50 = 157.6 µg/mL) and apparently surpassed that of commercial ribavirin (EC50 = 442.1 µg/mL) 2.8-fold. The preliminary antiviral mechanism was elaborately investigated via transmission electron microscopy, microscale thermophoresis (MST) determination, RT-qPCR, and Western blot analysis. The results showed that compound 7d blocked the assembly of TMV by binding with coat protein (Kd = 0.7 µM) and suppressed TMV coat protein gene expression and biosynthesis process. Computational simulations indicated that 7d displayed strong H-bonds and pi interactions with TMV coat protein, affording a lower binding energy (ΔGbind = -17.8 kcal/mol) compared with Ribavirin (ΔGbind = -10.7 kcal/mol). Overall, current results present a valuable perception of bisamide decorated benzotriazole derivatives with appreciably virustatic competence and should be profoundly developed as virucidal candidates in agrochemical.

Rhodamine-based fluorescent probe for dynamic STED imaging of mitochondria.

Stimulated emission depletion (STED) microscopy holds tremendous potential and practical implications in the field of biomedicine. However, the weak anti-bleaching performance remains a major challenge limiting the application of STED fluorescent probes. Meanwhile, the main excitation wavelengths of most reported STED fluorescent probes were below 500 nm or above 600 nm, and few of them were between 500-600 nm. Herein, we developed a new tetraphenyl ethylene-functionalized rhodamine dye (TPERh) for mitochondrial dynamic cristae imaging that was rhodamine-based with an excitation wavelength of 560 nm. The TPERh probe exhibits excellent anti-bleaching properties and low saturating stimulated radiation power in mitochondrial STED super-resolution imaging. Given these outstanding properties, the TPERh probe was used to measure mitochondrial deformation, which has positive implications for the study of mitochondria-related diseases.

Dissolved oxygen and ammonia affect ammonia production via GDH/AMPK signaling pathway and alter flesh quality in Chinese perch (Siniperca chuatsi).

The dissolved oxygen (DO) and ammonia are crucial to the growth of Chinese perch (Siniperca chuatsi). Information on the effects of DO and total ammonia nitrogen (TAN) in regulating ammonia nitrogen excretion and flesh quality in Chinese perch is scanty. This study aimed to evaluate the effects of dissolved DO at oxygen levels of 3 mg/L and 9 mg/L, as well as the TAN concentrations of 0.3 mg/L and 0.9 mg/L on ammonia excretion and flesh quality. Results showed that the ammonia contents in plasma, muscle, and liver of the 9 mg/L DO group were significantly higher than those of the 3 mg/L DO group (P < 0.05). However, the expression of AMPK-related signaling pathway genes (gdh, lkb1, and ampd) and flesh quality indicators (gumminess, chewiness, hardness) in the 9 mg/L DO group were significantly lower than those in the 3 mg/L DO group. Under long-term exposure to 0.9 mg/L TAN, the ammonia contents in plasma and gill filaments, as well as muscle flesh quality (resilience, gumminess, chewiness, cohesiveness), were significantly lower than those in the 0.3 mg/L TAN group (P < 0.05). However, the activities of GDH and AMPD enzymes in the 0.9 mg/L TAN group were significantly higher than those in the 0.3 mg/L TAN group. In summary, when fish are exposed to 3 mg/L DO and 0.9 mg/L TAN in the environment for a long time, their amino acids are used for transamination and deamination, resulting in insufficient energy supply for Chinese perch, whereas 9 mg/L DO and 0.9 mg/L TAN caused deterioration of the flesh quality.

Obliteration of portal venules contributes to portal hypertension in biliary cirrhosis.

The effects of the obliteration of portal venules (OPV) in cirrhotic portal hypertension are poorly understood. To investigate its contribution to portal hypertension in biliary cirrhosis and its underlying mechanism, we evaluated OPV using two-dimensional (2D) histopathology in liver explants from patients with biliary atresia (BA, n = 63), primary biliary cholangitis (PBC, n = 18), and hepatitis B-related cirrhosis (Hep-B-cirrhosis, n = 35). Then, three-dimensional (3D) OPV was measured by X-ray phase-contrast CT in two parallel models in rats following bile duct ligation (BDL) or carbon tetrachloride (CCl4) administration, representing biliary cirrhosis and post-necrotic cirrhosis, respectively. The portal pressure was also measured in the two models. Finally, the effects of proliferative bile ducts on OPV were investigated. We found that OPV was significantly more frequent in patients with biliary cirrhosis, including BA (78.57 ± 16.45%) and PBC (60.00 ± 17.15%), than that in Hep-B-cirrhotic patients (29.43 ± 14.94%, p < 0.001). OPV occurred earlier, evidenced by the paired liver biopsy at a Kasai procedure (KP), and was irreversible even after a successful KP in the patients with BA. OPV was also significantly more frequent in the BDL models than in the CCl4 models, as shown by 2D and 3D quantitative analysis. Portal pressure was significantly higher in the BDL model than that in the CCl4 model. With the proliferation of bile ducts, portal venules were compressed and irreversibly occluded, contributing to the earlier and higher portal pressure in biliary cirrhosis. OPV, as a pre-sinusoidal component, plays a key role in the pathogenesis of portal hypertension in biliary cirrhosis. The proliferated bile ducts and ductules gradually take up the 'territory' originally attributed to portal venules and compress the portal venules, which may lead to OPV in biliary cirrhosis. © 2024 The Pathological Society of Great Britain and Ireland.

Phase separation of SHP2E76K promotes malignant transformation of mesenchymal stem cells by activating mitochondrial complexes.

Mesenchymal stem cells (MSCs), suffering from diverse gene hits, undergo malignant transformation and aberrant osteochondral differentiation. Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2), a nonreceptor protein tyrosine phosphatase, regulates multicellular differentiation, proliferation, and transformation. However, the role of SHP2 in MSC fate determination remains unclear. Here, we showed that MSCs bearing the activating SHP2E76K mutation underwent malignant transformation into sarcoma stem-like cells. We revealed that the SHP2E76K mutation in mouse MSCs led to hyperactive mitochondrial metabolism by activating mitochondrial complexes I and III. Inhibition of complexes I and III prevented hyperactive mitochondrial metabolism and malignant transformation of SHP2E76K MSCs. Mechanistically, we verified that SHP2 underwent liquid-liquid phase separation (LLPS) in SHP2E76K MSCs. SHP2 LLPS led to its dissociation from complexes I and III, causing their hyperactivation. Blockade of SHP2 LLPS by LLPS-defective mutations or allosteric inhibitors suppressed complex I and III hyperactivation as well as malignant transformation of SHP2E76K MSCs. These findings reveal that complex I and III hyperactivation driven by SHP2 LLPS promotes malignant transformation of SHP2E76K MSCs and suggest that inhibition of SHP2 LLPS could be a potential therapeutic target for the treatment of activated SHP2-associated cancers.

Computer-assisted image analysis of preexisting histological patterns of the cephalic vein to predict wrist arteriovenous fistula non-maturation.

BACKGROUND: We used computer-assisted image analysis to determine whether preexisting histological features of the cephalic vein influence the risk of non-maturation of wrist fistulas. METHODS: This study focused on patients aged 20-80 years who underwent their first wrist fistula creation. A total of 206 patients participated, and vein samples for Masson's trichrome staining were collected from 134 patients. From these, 94 patients provided a complete girth of the venous specimen for automatic image analysis. Maturation was assessed using ultrasound within 90 days after surgery. RESULTS: The collagen to muscle ratio in the target vein, measured by computer-assisted imaging, was a strong predictor of non-maturation in wrist fistulas. Receiver operating characteristic analysis revealed an area under the curve of 0.864 (95% confidence interval of 0.782-0.946, p < 0.001). The optimal cut-off value for the ratio was 1.138, as determined by the Youden index maximum method, with a sensitivity of 89.0% and specificity of 71.4%. For easy application, we used a cutoff value of 1.0; the non-maturation rates for patients with ratios >1 and ≤ 1 were 51.7% (15 out of 29 patients) and 9.2% (6 out of 65 patients), respectively. Chi-square testing revealed significantly different non-maturation rates between the two groups (X2 (1, N = 94) = 20.9, p < 0.01). CONCLUSION: Computer-assisted image interpretation can help to quantify the preexisting histological patterns of the cephalic vein, while the collagen-to-muscle ratio can predict non-maturation of wrist fistula development at an early stage.

Highly birefringent side-hole fiber Bragg grating for high-temperature pressure sensing.

We demonstrate a novel, to the best of our knowledge, high-temperature pressure sensor based on a highly birefringent fiber Bragg grating (Hi-Bi FBG) fabricated in a dual side-hole fiber (DSHF). The Hi-Bi FBG is generated by a femtosecond laser directly written sawtooth structure in the DSHF cladding along the fiber core through the slow axis (i.e., the direction perpendicular to the dual-hole axis). The sawtooth structure serves as an in-fiber stressor and also generates Bragg resonance due to its periodicity. The DSHF was etched by hydrofluoric acid to increase its pressure sensitivity, and the diameter of two air holes was enlarged from 38.2 to 49.6 µm. A Hi-Bi FBG with a birefringence of up to 1.8 × 10-3 was successfully created in the etched DSHF. Two distinct reflection peaks could be observed by using a commercial FBG interrogator. Moreover, pressure measurement from 0 to 3 MPa at a high temperature of 700°C was conducted by monitoring the birefringence-induced peak splits and achieved a high-pressure sensitivity of -21.2 pm/MPa. The discrimination of the temperature and pressure could be realized by simultaneously measuring the Bragg wavelength shifts and peak splits. Furthermore, a wavelength-division-multiplexed (WDM) Hi-Bi FBG array was also constructed in the DSHF and was used for quasi-distributed high-pressure sensing up to 3 MPa. As such, the proposed femtosecond laser-inscribed Hi-Bi FBG is a promising tool for high-temperature pressure sensing in harsh environments, such as aerospace vehicles, nuclear reactors, and petrochemical industries.

Quantum spin liquid signatures in monolayer 1T-NbSe2.

Quantum spin liquids (QSLs) are in a quantum disordered state that is highly entangled and has fractional excitations. As a highly sought-after state of matter, QSLs were predicted to host spinon excitations and to arise in frustrated spin systems with large quantum fluctuations. Here we report on the experimental observation and theoretical modeling of QSL signatures in monolayer 1T-NbSe2, which is a newly emerging two-dimensional material that exhibits both charge-density-wave (CDW) and correlated insulating behaviors. By using scanning tunneling microscopy and spectroscopy (STM/STS), we confirm the presence of spin fluctuations in monolayer 1T-NbSe2 by observing the Kondo resonance as monolayer 1T-NbSe2 interacts with metallic monolayer 1H-NbSe2. Subsequent STM/STS imaging of monolayer 1T-NbSe2 at the Hubbard band energy further reveals a long-wavelength charge modulation, in agreement with the spinon modulation expected for QSLs. By depositing manganese-phthalocyanine (MnPc) molecules with spin S = 3/2 onto monolayer 1T-NbSe2, new STS resonance peaks emerge at the Hubbard band edges of monolayer 1T-NbSe2. This observation is consistent with the spinon Kondo effect induced by a S = 3/2 magnetic impurity embedded in a QSL. Taken together, these experimental observations indicate that monolayer 1T-NbSe2 is a new promising QSL material.

Aerosol inhalation of inflammatory cells-targeted dendrimer-dexamethasone conjugate for efficient allergic asthma therapy.

Allergic asthma (AA) is a common breathing disorder clinically characterized by the high occurrence of acute and continuous inflammation. However, the current treatment options for AA are lacking in effectiveness and diversity. In this study, we determined that the cell membrane receptor of gamma-glutamyl transferase (GGT) was highly overexpressed on the inflammatory cells that infiltrate the pulmonary tissues in AA cases. Therefore, we developed a GGT-specific dendrimer-dexamethasone conjugate (GSHDDC) that could be administered via aerosol inhalation to treat AA in a rapid and sustained manner. The GSHDDC was fabricated by the covalent attachment of 6-hydroxyhexyl acrylate-modified dexamethasone to polyamidoamine dendrimers via a carbonic ester linkage and the amino Michael addition, followed by the surface modification of the dendrimers with the GGT substrate of glutathione. After aerosol inhalation by the AA mice, the small particle-sized GSHDDC could easily diffuse into pulmonary alveoli and touch with the inflammatory cells via the glutathione ligand/GGT receptor-mediated recognition. The overexpressed GGT on the surface of inflammatory cells then triggers the gamma-glutamyl transfer reactions of glutathione to generate positively charged primary amines, thereby inducing rapid cationization-mediated cellular endocytosis into the inflammatory cells. The dexamethasone was gradually released by the intracellular enzyme hydrolysis, enabling sustained anti-inflammatory effects (e.g., reducing eosinophil infiltration, decreasing the levels of inflammatory factors) in the ovalbumin-induced AA mice. This study demonstrates the effectiveness of an inhalational and active inflammatory cells-targeted dendrimer-dexamethasone conjugate for efficient AA therapy.

Rapid and accurate identification of marine bacteria spores at a single-cell resolution by laser tweezers Raman spectroscopy and deep learning.

Marine bacteria have been considered as important participants in revealing various carbon/sulfur/nitrogen cycles of marine ecosystem. Thus, how to accurately identify rare marine bacteria without a culture process is significant and valuable. In this work, we constructed a single-cell Raman spectra dataset from five living bacteria spores and utilized convolutional neural network to rapidly, accurately, nondestructively identify bacteria spores. The optimal CNN architecture can provide a prediction accuracy of five bacteria spore as high as 94.93% ± 1.78%. To evaluate the classification weight of extracted spectra features, we proposed a novel algorithm by occluding fingerprint Raman bands. Based on the relative classification weight arranged from large to small, four Raman bands located at 1518, 1397, 1666, and 1017 cm-1 mostly contribute to producing such high prediction accuracy. It can be foreseen that, LTRS combined with CNN approach have great potential for identifying marine bacteria, which cannot be cultured under normal condition.

Ultrasonic microbubbles promote mesenchymal stem cell homing to the fibrotic liver via upregulation of CXCR4 expression.

OBJECTIVE: To investigate the mechanism of ultrasound microbubbles (UTMB) promoting stem cells homing to fibrotic liver. METHODS: Bone marrow derived mesenchymal stem cells (BMSCs) were divided into 5 groups with or without ultrasound microbubbles and continuously irradiated with ultrasound conditions of frequency 1 MHZ and output power 0.6 W/cm2 for different times, and then injected into a mouse model of liver fibrosis through the tail vein with or without ultrasound microbubbles, with sound intensity. The effect of ultrasound microbubbles on MSC expression of CXC chemokine receptor 4 (CXCR4) and homing fibrotic liver was evaluated by flow cytometry (FCM), western blot (WB) and immunohistochemistry (IHC) analysis. RESULTS: The level of CXCR4 expression was significantly higher in the ultrasound microbubble group than in the non-intervention group (P < 0.05), and the number of MSC and the rate of CXCR4 receptor positivity in the ultrasound microbubble-treated liver tissues were significantly higher than in the non-intervention group (P < 0.01). CONCLUSION: Ultrasonic microbubbles can promote the expression of CXCR4 on the surface of MSCs, thus improving the homing rate of MSCs in fibrotic liver.