GLUT1 regulates the release of VEGF-A in the alveolar epithelium of lipopolysaccharide-induced acute lung injury.

Acute lung injury (ALI) is a severe disease with high mortality and poor prognosis, characterized by excessive and uncontrolled inflammatory response. Vascular endothelial growth factor A (VEGF-A) contributes to the development and progression of ALI. The aim of this study was to evaluate the role of glucose transporter 1 (GLUT1) in alveolar epithelial VEGF-A production in lipopolysaccharide (LPS)-induced ALI. An ALI mouse model was induced by LPS oropharyngeal instillation. Mice were challenged with LPS and then treated with WZB117, a specific antagonist of GLUT1. For the vitro experiments, cultured A549 cells (airway epithelial cell line) were exposed to LPS, with or without the GLUT1 inhibitors WZB117 or BAY876. LPS significantly upregulated of GLUT1 and VEGF-A both in the lung from ALI mice and in cultured A549. In vivo, treatment with WZB117 not only markedly decreased LPS-induced pulmonary edema, injury, neutrophilia, as well as levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF), but also reduced VEGF-A production. Yet, the maximum tolerated concentration of WZB117 failed to suppress LPS-induced VEGF-A overexpression in vitro. While administration of BAY876 inhibited gene and protein expression as well as secretion of VEGF-A in response to LPS in A549. These results illustrated that GLUT1 upregulates VEGF-A production in alveolar epithelia from LPS-induced ALI, and inhibition of GLUT1 alleviates ALI.

The Trend of the Treatment of Advanced Hepatocellular Carcinoma: Combination of Immunotherapy and Targeted Therapy.

OPINION STATEMENT: Hepatocellular carcinoma (HCC) is a common type of tumor worldwide. The development of systemic treatment of advanced HCC has remained stagnant for a considerable period. During the last years, a series of new treatment regimens based on the combination of immunotherapeutic drugs and targeted drugs have been gradually developed, increased the objective response rate (ORR), overall survival (OS), and progression free survival (PFS) of HCC patients. Among the different combination therapy groups, atezolizumab plus bevacizumab and sintilimab plus IBI-305 seem to have unique advantages, while head-to-head comparisons are still needed. A comprehensive understanding of the developments, the ongoing clinical trials and the mechanisms of combination of immunotherapy and targeted therapy might lead to the development of new combination strategies and solving current challenges such as the molecular biomarkers, the clinical administration order of drugs and the second-line treatments after combination therapy.

An emerging master inducer and regulator for epithelial-mesenchymal transition and tumor metastasis: extracellular and intracellular ATP and its molecular functions and therapeutic potential.

Despite the rapid development of therapeutic strategies in cancer treatment, metastasis remains the major cause of cancer-related death and scientific challenge. Epithelial-Mesenchymal Transition (EMT) plays a crucial role in cancer invasion and progression, a process by which tumor cells lose cell-cell adhesion and acquire increased invasiveness and metastatic activity. Recent work has uncovered some crucial roles of extracellular adenosine 5'- triphosphate (eATP), a major component of the tumor microenvironment (TME), in promoting tumor growth and metastasis. Intratumoral extracellular ATP (eATP), at levels of 100-700 µM, is 103-104 times higher than in normal tissues. In the current literature, eATP's function in promoting metastasis has been relatively poorly understood as compared with intracellular ATP (iATP). Recent evidence has shown that cancer cells internalize eATP via macropinocytosis in vitro and in vivo, promoting cell growth and survival, drug resistance, and metastasis. Furthermore, ATP acts as a messenger molecule that activates P2 purinergic receptors expressed on both tumor and host cells, stimulating downstream signaling pathways to enhance the invasive and metastatic properties of tumor cells. Here, we review recent progress in understanding eATP's role in each step of the metastatic cascade, including initiating invasion, inducing EMT, overcoming anoikis, facilitating intravasation, circulation, and extravasation, and eventually establishing metastatic colonization. Collectively, these studies reveal eATP's important functions in many steps of metastasis and identify new opportunities for developing more effective therapeutic strategies to target ATP-associated processes in cancer.

Properties of Ni-Al2O3 composite coating by laser-assisted pulse electrodeposition.

To study the influence of laser process parameters on the surface properties of the coating, N i-A l 2 O 3 composite coatings on 304 stainless-steel sheets with laser-assisted pulsed electrodeposition was proposed in this paper. Laser single pulse energy and scanning speed were selected as research factors. Single-factor experiments were performed to investigate the effect of various factors on the surface morphology, particle mass fraction, microhardness, surface roughness, and corrosion resistance of the composite coating. The experimental results show that the surface properties of the composite coating first increase and then decrease with increasing laser single pulse energy. When the laser single pulse energy is 11 µJ, the minimum surface roughness value is 0.380 µm with a smooth and uniform coating surface and the best surface morphology. Moreover, as the scanning speed increases, the corrosion resistance of the composite coating initially increases and then decreases. The corrosion resistance of the composite coatings is best with a scanning speed of 1000 mm/s. When the scanning speed was 1500 mm/s, the particle mass fraction in the coating reached a maximum of 1.984%; meanwhile, the highest hardness of the composite coating was obtained with the value of 476.38 HV.

Identification of Gentian-Related Species Based on Two-Dimensional Correlation Spectroscopy (2D-COS) Combined with Residual Neural Network (ResNet).

Gentian is a traditional Chinese herb with heat-clearing, damp-drying, inflammation-alleviating and digestion-promoting effects, which is widely used in clinical practice. However, there are many species of gentian. According to the pharmacopoeia, Gentiana manshurica Kitag, Gentiana scabra Bge, Gentiana triflora Pall and Gentianarigescens Franch are included. Therefore, accurately identifying the species of gentian is important in clinical use. In recent years, with the advantages of low cost, convenience, fast analysis and high sensitivity, infrared spectroscopy (IR) has been extensively used in herbal identification. Unlike one-dimensional spectroscopy, a two-dimensional correlation spectrum (2D-COS) can improve the resolution of the spectrum and better highlight the details that are difficult to detect. In addition, the residual neural network (ResNet) is an important breakthrough in convolutional neural networks (CNNs) for significant advantages related to image recognition. Herein, we propose a new method for identifying gentian-related species using 2D-COS combined with ResNet. A total of 173 gentian samples from seven different species are collected in this study. In order to eliminate a large amount of redundant information and improve the efficiency of machine learning, the extracted feature band method was used to optimize the model. Four feature bands were selected from the infrared spectrum, namely 3500-3000 cm-1, 3000-2750 cm-1, 1750-1100 cm-1 and 1100-400 cm-1, respectively. The one-dimensional spectral data were converted into synchronous 2D-COS images, asynchronous 2D-COS images, and integrative 2D-COS images using Matlab (R2022a). The identification strategy for these three 2D-COS images was based on ResNet, which analyzes 2D-COS images based on single feature bands and full bands as well as fused feature bands. According to the results, (1) compared with the other two 2D-COS images, synchronous 2D-COS images are more suitable for the ResNet model, and (2) after extracting a single feature band 1750-1100 cm-1 to optimize ResNet, the model has the best convergence performance, the accuracy of training, test and external validation is 1 and the loss value is only 0.155. In summary, 2D-COS combined with ResNet is an effective and accurate method to identify gentian-related species.

Wound dehiscence in enhanced recovery after open radical cystectomy: A meta-analysis.

A meta-analysis study to assess the outcome of enhanced recovery (ER) after radical cystectomy (RC) on wound dehiscence was performed. A comprehensive literature examination till January 2023 was implemented and 1457 linked studies were appraised. The picked studies contained 772 open RC subjects in the picked studies' baseline, 436 of them were enhanced recovery after RC, and 336 were open RC. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to calculate the consequence of enhanced recovery after RC on wound dehiscence after open RC by the dichotomous styles and a fixed or random model. The ER after RC caused significantly lower wound dehiscence (OR, 0.51; 95% CI, 0.30-0.89, P = .02) with low heterogeneity (I2  = 46%) compared with open RC. The ER after RC caused significantly lower wound dehiscence compared with open RC. Thorough precaution should be taken when commerce with the consequences because a limited number of studies were found and selected for this meta-analysis.

High PLA2 level is correlated with glioblastoma progression via regulating DNA replication.

Phospholipases A2 (PLA2) are a superfamily of enzymes, playing a critical role in the development of various human cancers. However, the mechanism of PLA2 as an oncogene in glioblastoma remains largely unknown. In this study, we explored the effects of PLA2 on glioblastoma and investigated the underlying mechanism. The results showed that PLA2 was highly expressed in glioblastoma. Patients with a high PLA2 level have low overall survival than those with low PLA2 expression. PLA2 overexpression promoted glioblastoma cell proliferation and viability and inhibited cell apoptosis by inducing cell cycle transition from G1 to S stage. Knockdown of PLA2 inhibited tumor growth in the xenograft mice model. In addition, PLA2 knockdown decreased the protein level of MCM2 and MCM5. These findings identify PLA2 as an oncogene in glioblastoma progression and provide a promising strategy to treat glioblastoma in the future.

Selective acceleration of 2-hydroxyl pyridine mono-oxygenation using specially acclimated biomass.

Biodegradation of pyridine starts with two mono-oxygenation reactions, and 2-hydroxyl pyridine (2-HP) accumulates as pyridine is mono-oxygenated in the first reaction. The accumulation of 2-HP inhibits both initial reactions. Therefore, selective acceleration of the second mono-oxygenation reaction should significantly enhance pyridine transformation and mineralization. Activated-sludge biomass was separately acclimated with pyridine or 2-HP to produce pyridine- and 2-HP-acclimated biomasses. The pyridine-acclimated biomass was superior for pyridine biodegradation, but the 2-HP-acclimated biomass was superior for 2-HP biodegradation. As a consequence, the pyridine-acclimated biomass by itself achieved faster mono-oxygenation of pyridine to 2-HP, but 2-HP accumulated, which limited mineralization to 60%. In contrast, mineralization reached 90% when one-third of the pyridine-acclimated was replaced with 2-HP-acclimated biomass, because 2-HP did not accumulate during pyridine biodegradation. The lack of 2-HP accumulation relieved its inhibition: e.g., the pyridine removal rates, normalized to the mass of pyridine-acclimated biomass, increased from 0.52 to 0.57 mM0.5⋅h-1 when one-third of the pyridine-acclimated biomass was replaced by 2-HP-acclimated biomass. Phylogenetic analysis showed that microbiological communities of pyridine-acclimated biomass and 2-HP-acclimated biomass differed in important ways. On the one hand, the 2-HP-acclimated biomass was richer and dominated by a rare biosphere, or genera having <0.1% of total reads. On the other hand, the most-enriched genus in the pyridine-acclimated community (Methylibium) is associated with the first mono-oxygenation of pyridine, while enriched genera in the 2-HP-acclimated community (Sediminibacterium and Dokdonella) are associated with the second mono-oxygenation of pyridine.

Assessment of CD27 expression on T-cells as a diagnostic and therapeutic tool for patients with smear-negative pulmonary tuberculosis.

BACKGROUND: There is a global focus on illness diagnosis in smear-negative and latent tuberculosis infectious populations (SN-TB and LTBI). CD27 has been suggested to play a direct role in active TB. Little is known about smear-negative individuals. Here, we tried to investigate whether it has a role in smear-negative populations. The expression of CD27 and MTB-specific CD27 in CD4+ T cells ("CD27-CD4+" and "CD27-IFN-γ+CD4+") was evaluated in MTB-unexposed controls (HC), TB contacts (TB-C) and SN-TB individuals by flow cytometry. The sensitivity, specificity and AUC (area under curve) of "CD27-IFN-γ+CD4+" cells to distinguish SN-TBs from HCs and TB-Cs were determined by receiver operating characteristic (ROC) curve analysis. The clinical index was selected from the clinical laboratory and evaluated for correlation with "CD27-IFN-γ+CD4+" cells by Spearman statistical analysis. RESULTS: We observed that the percentages of "CD27-IFN-γ+CD4+" cells were significantly increased in the SN-TB group compared with the HC and TB-C groups (AUC was 0.88, sensitivity was 82.14%, specificity was 80.00%, and P < 0.0001). The percentage of "CD27-IFN-γ+CD4+" cells was negatively correlated with WBC (white blood cell count) (r = - 0.3019, P = 0.0182) and positively correlated with IgE (immunoglobulin E) (r = 0.2805, P = 0.0362). Furthermore, "CD27-IFN-γ+CD4+" cells were significantly decreased, especially in the > 50 years group, after clinical treatment. CONCLUSION: The present results demonstrated that the percentage of "CD27-IFN-γ+CD4+" cells might be a conceivable molecular indicator in the diagnosis of SN-TB and was influenced by its outcome of therapy.

Effects of carboxylated multi-walled carbon nanotubes on bioconcentration of pentachlorophenol and hepatic damages in goldfish.

Carboxylated multi-walled carbon nanotubes (MWCNT-COOH) exerts strong adsorption capacity for pentachlorophenol (PCP) and they inevitably co-occur in the environment, but few studies have characterized the effects of MWCNT-COOH on the bioavailability of PCP and its oxidative and tissue damages to fish. In this work, we assessed the PCP accumulation in different organs and the induced oxidative and tissue damages of goldfish following 50-d in vivo exposure to PCP alone or co-exposure with MWCNT-COOH. Our results indicated that PCP bioaccumulation in goldfish liver, gill, muscle, intestine and gut contents was inhibited after co-exposure with MWCNT-COOH in uptake phase. PCP exposure alone and co-exposure with MWCNT-COOH evoked severe oxidative and tissue damages in goldfish bodies, as indicated by significant inhibition of activities of antioxidant enzymes, remarkable decrease in glutathione level, simultaneous elevation of malondialdehyde content, and obvious histological damages to liver and gill. The decreased accumulation of PCP in the presence of MWCNT-COOH led to the reduction of PCP-induced toxicity to liver tissues, as confirmed by the alleviation of hepatic oxidative damages. However, co-exposure groups had higher concentrations of PCP in the tissues than PCP treatment alone (p < 0.05 each) in the depuration phase, revealing that MWCNT-COOH-bound pollutants might pose higher risk once desorbed from the nanoparticles. These results provided substantial information regarding the combined effects of PCP and MWCNT-COOH on aquatic species, which helps to deeply understand the potential ecological risks of the emerging pollutants.

Abscisic acid suppresses the activation of NLRP3 inflammasome and oxidative stress in murine allergic airway inflammation.

Abscisic acid (ABA), a well-known natural phytohormone reportedly exerts anti-inflammatory and anti-oxidative properties in diabetes and colitis. However, the efficacy of ABA against allergic airway inflammation and the underlying mechanism remain unknown. Herein, an OVA-induced murine allergic airway inflammation model was established and treated with ABA in the presence or absence of PPAR-γ antagonist GW9662. The results showed that ABA effectively stunted the development of airway inflammation, and concordantly downregulated OVA-induced activation of NLRP3 inflammasome, suppressed oxidative stress and decreased the expression of mitochondrial fusion/fission markers including Optic Atrophy 1 (OPA1), Mitofusion 2 (Mfn2), dynamin-related protein 1 (DRP1) and Fission 1 (Fis1). Moreover, ABA treatment further increased OVA-induced expression of PPAR-γ, while GW9662 abrogated the inhibitory effect of ABA on allergic airway inflammation as well as on the activation of NLRP3 inflammasome and oxidative stress. Consistently, ABA inhibited the activation of NLRP3 inflammasome, suppressed oxidative stress and mitochondrial fusion/fission in LPS-stimulated Raw264.7 cells via PPAR-γ. Collectively, ABA ameliorates OVA-induced allergic airway inflammation in a PPAR-γ dependent manner, and such effect of ABA may be associated with its inhibitory effect on NLRP3 inflammasome and oxidative stress. Our results suggest the potential of ABA or ABA-rich food in protecting against asthma.

Extracellular and macropinocytosis internalized ATP work together to induce epithelial-mesenchymal transition and other early metastatic activities in lung cancer.

BACKGROUND: Extracellular ATP (eATP) was shown to induce epithelial-mesenchymal transition (EMT), a very important early process in metastasis, in cancer cells via purinergic receptor signaling. However, the exact induction mechanisms are far from fully known. We previously described that eATP is internalized by cancer cells in vitro and in vivo by macropinocytosis in human non-small cell lung cancer A549 and other cancer cells, drastically elevates intracellular ATP levels, enhances cell proliferation and resistance to anticancer drugs. In this study, we tested the hypothesis that eATP and macropinocytosis-internalized eATP also induces EMT and other early steps of metastasis. METHODS: Floating cells, fencing, and transwell assays were used to show that ATP induces cell detachment, new colony formation, migration and invasion in human A549 and other lung cancer cells. Western blots were used to detect ATP-induced changes in EMT-related proteins; Confocal microscopy was used to demonstrate ATP-induced metastasis-related cell morphological changes. Inhibitors and siRNA knockdowns were used to determine P2X7's involvement in the ATP-induced EMT. CRISPR-Cas9 knockout of the SNX5 gene was used to identify macropinocytosis' roles in EMT and cancer cell growth both in vitro and in vivo. Student t-test and one-way ANOVA were used to determine statistical significance, P < 0.05 was considered significant. RESULTS: eATP potently induces expression of matrix metallopeptidases (MMPs), and detachment, EMT, migration, and invasion of lung cancer cells. The induction was independent of TGF-ß and semi-independent of P2X7 activation. eATP performs these functions not only extracellularly, but also intracellularly after being macropinocytically internalized to further enhance P2X7-mediated EMT, filopodia formation and other early steps of metastasis. The knockout of macropinocytosis-associated SNX5 gene significantly reduces macropinocytosis, slows down tumor growth, and changes tumor morphology in nude mice. CONCLUSIONS: Collectively, these results show that eATP's functions in these processes not only from outside of cancer cells but also inside after being macropinocytotically internalized. These findings shed light on eATP's initiator and effector roles in almost every step in early metastasis, which calls for rethinking and rebalancing energy equations of intracellular biochemical reactions and the Warburg effect, and identifies eATP and macropinocytosis as novel targets for potentially slowing down EMT and preventing metastasis.

Au-Catalyzed tandem intermolecular hydroalkoxylation/Claisen rearrangement between allylic alcohols and chloroalkynes.

An efficient protocol for the synthesis of γ,δ-unsaturated α-chloroketones has been developed via Au-catalyzed tandem intermolecular hydroalkoxylation/Claisen rearrangement. In the presence of 1 mol% JohnPhosAuCl and 1 mol% NaBArF, a broad range of allylic alcohols smoothly underwent the tandem intermolecular hydroalkoxylation/Claisen rearrangement with aromatic, vinylic or aliphatic chloroalkynes to give structurally diverse γ,δ-unsaturated α-chloroketones in excellent yields. Importantly, high Z/E selectivity was achieved. Other advantages are widespread availability of the substrates, compatibility with a broad range of functional groups and mild reaction conditions.

Effects of Various Carbon Nanotubes on Soil Bacterial Community Composition and Structure.

Carbon nanotubes (CNTs) have huge industrial potential, and their environmental impacts need to be evaluated. Knowledge of CNT impacts on soil microbial communities is still limited. To address this knowledge gap, we systematically examined dynamic effects of one type of single-walled carbon nanotubes (SWs) and three multiwalled carbon nanotubes (MWs) with different outer diameters on the soil bacterial community in an agricultural soil over 56 days. The results showed that SWs differently affected soil bacterial abundance, diversity, and composition as compared to MWs. The differences could have resulted from the materials' distinct physical structure and surface composition, which in turn affected their bioavailability in soil. For certain treatments, soil bacterial diversity and the relative abundance of certain predominant phyla were correlated with their exposure duration. However, many phyla recovered to their initial relative abundance within 56 days, reflecting resilience of the soil bacterial community in response to CNT-induced disturbance. Further analysis at the genus level showed differential tolerance to MWs, as well as size- and dose-dependent tolerance among bacterial genera. Predictive functional profiling showed that while CNTs initially caused fluctuations in microbial community function, community function largely converged across all treatments by the end of the 56 day exposure.

Humic Acid Can Enhance the Mineralization of Phenanthrene Sorbed on Biochars.

Biodegradation of hydrophobic organic contaminants by bacteria has been widely studied, but how dissolved organic matter (DOM) may affect their removal if accumulated on biochars is poorly understood. To address this knowledge gap, microbial mineralization of phenanthrene (PHE) spiked on various biochars by Mycobacterium vanbaalenii PYR-1 in the presence of humic acid (HA, a model DOM) at two concentrations was investigated. Our findings showed that HA greatly increased the rate and extent of PHE mineralization. This could be attributed to enhanced PHE desorption by HA, which facilitated access to it by bacteria in the aqueous phase. Furthermore, the high HA affinity for PHE facilitated PHE flow toward the bacterial cells with HA acting as a carrier in the aqueous phase. The mineralization enhancement of PHE by HA within 480 h was negatively influenced by the aromatic carbon contents and micropore volumes in biochars. This shows the importance of the physicochemical properties of biochars in altering the HA effect. Results of this study provide novel information on how to achieve complete removal of PHE accumulated on biochars with a strong sorption affinity for it, using a microbial technique and natural DOM.

The calcineruin inhibitor cyclosporine a synergistically enhances the susceptibility of Candida albicans biofilms to fluconazole by multiple mechanisms.

BACKGROUND: Biofilms produced by Candida albicans (C. albicans) are intrinsically resistant to fungicidal agents, which are a main cause of the pathogenesis of catheter infections. Several lines of evidence have demonstrated that calcineurin inhibitor FK506 or cyclosporine A (CsA) can remarkably enhance the antifungal activity of fluconazole (FLC) against biofilm-producing C. albicans strain infections. The aim of present study is thus to interrogate the mechanism underpinning the synergistic effect of FLC and calcineurin inhibitors. RESULTS: Twenty four clinical C. albicans strains isolated from bloodstream showed a distinct capacity of biofilm formation. A combination of calcineurin inhibitor CsA and FLC exhibited a dose-dependent synergistic antifungal effect on the growth and biofilm formation of C. albicans isolates as determined by a XTT assay and fluorescent microscopy assay. The synergistic effect was accompanied with a significantly down-regulated expression of adhesion-related genes ALS3, hypha-related genes HWP1, ABC transporter drug-resistant genes CDR1 and MDR1, and FLC targeting gene, encoding sterol 14alpha-demethylase (ERG11) in clinical C. albicans isolates. Furthermore, an addition of CsA significantly reduced the cellular surface hydrophobicity but increased intracellular calcium concentration as determined by a flow cytometry assay (p < 0.05). CONCLUSION: The results presented in this report demonstrated that the synergistic effect of CsA and FLC on inhibited C. albicans biofilm formation and enhanced susceptibility to FLC was in part through a mechanism involved in suppressing the expression of biofilm related and drug-resistant genes, and reducing cellular surface hydrophobicity, as well as evoking intracellular calcium concentration.

Unveiling potential drug targets for lung squamous cell carcinoma through the integration of druggable genome and genome-wide association data.

Background: Lung squamous cell carcinoma (LSCC) is a major subtype of lung cancer with poor prognosis and low survival rate. Compared with lung adenocarcinoma, yet no FDA-approved targeted-therapy has been found for lung squamous cell carcinoma. Methods: To identify potential drug targets for LSCC, Summary-data-based Mendelian randomization (SMR) analysis was used to examine the potential association between 4,543 druggable genes and LSCC, followed by colocalization analysis and HEIDI tests to confirm the robustness of the result. Phenome-wide association study (PheWAS) explored potential side effects of candidate drug targets. Enrichment analysis and protein-protein interaction networks revealed the function and significance of therapeutic targets. Single-cell expression analysis was used to examine cell types with enrichment expression of druggable genes in LSCC tissue. Drug prediction included screening potential drug candidates and evaluating their interactions with targets through molecular docking. Results: This research has identified ten significant drug targets for LSCC through a comprehensive SMR analysis. These targets included (COPA, PKD2L1, CCR1, C2, CYP21A2, and NCSTN as risk factors, and CCNA2, C4A, APOM, and LPAR2 as protective factors). PheWAS demonstrated that C2, CCNA2, LPAR2, and NCSTN exhibited associations with other phenotypes at the genetic level. Then, we found four potentially effective drugs with the Dsigdb database. Subsequently, molecular docking indicated that favorable binding interactions between drug candidates and potential target molecules. In the druggability evaluation, five out of ten drug target genes have been used in drug development (APOM, C4A, CCNA2, COPA, and PKD2L1). Six out of ten druggable genes showed significant expression in LSCC tissues (COPA, PKD2L1, CCR1, C2, NCSTN, LPAR2). Besides, Single-cell expression analysis revealed that C2 and CCNA2 were primarily enriched in macrophages, while COPA and NCSTN were enriched in both macrophages and epithelial cells. Conclusion: Our research revealed ten potential druggable genes for LSCC treatment, which might help to advance the precise and efficient therapeutic approaches of LSCC.

Carboxymethyl chitosan-based nanoparticles of acid response for the synergistic anti-tumor effect of PDT and chemotherapy.

The combination of multiple anti-tumor methods has shown significant application potential in overcoming the limitations of monotherapy. Photodynamic therapy (PDT) and chemotherapy combination is a promising strategy for reducing drug resistance and side effects. Here, inspired by the acidic environment of tumors, carboxymethyl chitosan-based pH-responsive nanovesicles were developed to co-deliver the chemotherapeutic drug doxorubicin (DOX) and photosensitizer 5-aminolevulinic acid (5-ALA). The in vitro drug release studies revealed that drugs could be responsively released when nanoparticles were triggered by the acidic environment. The controlled-release behavior improved drug retention and reduced the administration time. Our nanoparticles could significantly enhance the killing effect of drugs on tumor cells and increase intracellular levels of reactive oxygen species (ROS) compared to monotherapy, effectively achieving the effects of combined chemotherapy and PDT. The loaded DOX could kill tumor cells and the loaded 5-ALA could enhance the content of protoporphyrin IX (PpIX), resulting in excess ROS production to improve the effects of PDT. In summary, our nanoparticles could co-deliver the drugs and exert synergistical anti-tumor of PDT and chemotherapy by suppressing tumor cell proliferation and facilitating cell apoptosis.

Novel bio-inspired soft actuators for upper-limb exoskeletons: design, fabrication and feasibility study.

Soft robots have been increasingly utilized as sophisticated tools in physical rehabilitation, particularly for assisting patients with neuromotor impairments. However, many soft robotics for rehabilitation applications are characterized by limitations such as slow response times, restricted range of motion, and low output force. There are also limited studies on the precise position and force control of wearable soft actuators. Furthermore, not many studies articulate how bellow-structured actuator designs quantitatively contribute to the robots' capability. This study introduces a paradigm of upper limb soft actuator design. This paradigm comprises two actuators: the Lobster-Inspired Silicone Pneumatic Robot (LISPER) for the elbow and the Scallop-Shaped Pneumatic Robot (SCASPER) for the shoulder. LISPER is characterized by higher bandwidth, increased output force/torque, and high linearity. SCASPER is characterized by high output force/torque and simplified fabrication processes. Comprehensive analytical models that describe the relationship between pressure, bending angles, and output force for both actuators were presented so the geometric configuration of the actuators can be set to modify the range of motion and output forces. The preliminary test on a dummy arm is conducted to test the capability of the actuators.

Resveratrol-loaded sulfated Hericium erinaceus ß-glucan-chitosan nanoparticles: Preparation, characterization and synergistic anti-inflammatory effects.

Resveratrol (RES) is a natural polyphenol with excellent biological activity. But the poor stability and bioavailability of RES severely limit its application. Thus, the resveratrol-loaded sulfated Hericium erinaceus ß-glucan-chitosan nanoparticles (DS-CS-RES NPs) were prepared using electrostatic self-assembly to solve these problems in this study. The structure of DS-CS-RES NPs was spherical or sub spherical shape with small average particle size (191.07 nm), which was characterized by FT-IR, FS, XRD and TEM. DS-CS-RES NPs exhibited good stability and RES had a sustainable release from the nanoparticles in gastrointestinal digestion. Meanwhile, DS-CS-RES NPs could improve the inflammatory injury of LPS stimulated RAW264.7 macrophages by inhibiting the production of NO, IL-1ß, IL-6 and TNF-α. Furthermore, DS-CS-RES NPs had strong anti-inflammatory activity by regulating protein levels of NF-κB p65, STAT1 and TLR4 through NF-κB and JAK-STAT1 signaling pathway in vitro, and sulfated H. erinaceus ß-glucan-chitosan nanoparticle (DS-CS NPs) and RES had synergistic anti-inflammatory effect. Overall, DS-CS NPs can serve as a potential green and safe functional carrier for encapsulating resveratrol, which can improve its anti-inflammatory activity. This work may be conducive to the development of functional carrier for encapsulating RES and applications of hydrophobic active molecules in functional foods or medicines.