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Meloxicam (MLX) is a commonly used drug in the clinical treatment of osteoarthritis, but it is associated with gastrointestinal adverse reactions. Therefore, in this study, we developed a sustained-release microsphere formulation of MLX for topical administration of knee joint. The MLX-loaded PLGA microspheres (MLX-MS) were prepared by emulsion solvent evaporation method with optimization of formulation using orthogonal experimental design. Physicochemical characterization results show MLX-MS were spherical with a smooth surface, the particle size was about 100 μm, drug loading was 30%, and encapsulation efficiency was 76.8%. In addition, the in vivo pharmacokinetics, tissue distribution, and pharmacodynamics were evaluated in rats by intra-articular administration of MLX. The microspheres showed a typical long-term sustained release pattern with a low initial burst release. In contrast to oral administration, local injection of MLX-MS produced a much higher value of elimination half-life time(T1/2) and peak time (Tmax) in plasma, while the intestinal drug distribution was significantly decreased. MLX-MS could also cause a greater reduction in the body level of IL-6 and TNF-α, which was positively correlated with R2=0.981. A good linear relationship (R2 = 0.9945) between the in vitro and in vivo drug release from MLX-MS could be observed, bivariate correlation analysis. All the findings demonstrated that local administration of MLX-MS can prolong the action time of MLX and reduce side effects, thus would be a promising preparation for the treatment of arthritis.

Silk fibroin has been widely used in biological fields due to its biocompatibility, mechanical properties, biodegradability, and safety. Recently, silk fibroin as a drug carrier was developed rapidly and achieved remarkable progress in cancer treatment. The silk fibroin-based delivery system could effectively kill tumor cells without significant side effects and drug resistance. However, few studies have been reported on silk fibroin delivery systems for antitumor therapy. The advancement of silk fibroin-based drug delivery systems research and its applications in cancer therapy are highlighted in this study. The properties, applications, private opinions, and future prospects of silk fibroin carriers are discussed to understand better the development of anti-cancer drug delivery systems, which may also contribute to advancing silk fibroin innovation.

Objectives: Network pharmacological methods were used to investigate the underlying molecular mechanisms of LianXia NingXin (LXNX) formula, a Chinese prescription, to treat coronary heart disease (CHD) and disease phenotypes (CHD related diseases and symptoms).Methods: The different seed gene lists associated with the herbs of LXNX formula, the CHD co-morbid diseases and symptoms which were relieved by the LXNX formula (co-morbid diseases and symptoms) were curated manually from biomedical databases and published biomedical literatures. Module enrichment analysis was used to identify CHD-related disease modules in the protein–protein interaction (PPI) network which were also associated to the targets of LXNX formula (LXNX formula’s CHD modules). The molecular characteristics of LXNX formula’s CHD modules were investigated via functional enrichment analysis in terms of gene ontology and pathways. We performed shortest path analysis to explore the interactions between the drug targets of LXNX formula and CHD related disease phenotypes (e.g., co-morbid diseases and symptoms).Results: We identified two significant CHD related disease modules (i.e., M146 and M203), which were targeted by the herbs of LXNX formula. Pathway and GO term functional analysis results indicated that G-protein coupled receptor signaling pathways (GPCR) of M146 and cellular protein metabolic process of M203 are important functional pathways for the respective module. This is further confirmed by the shortest path analysis between the drug targets of LXNX formula and the aforementioned disease modules. In addition, corticotropin releasing hormone (CRH) and natriuretic peptide precursor A (NPPA) are the only two LXNX formula target proteins with the low shortest path length (on average shorter than 3) to their respective CHD module and co-morbid disease and symptom gene groups.Conclusion: G-protein coupled receptor signaling pathway and cellular protein metabolic process are the key LXNX formula’s pathways to treat CHD disease phenotypes, in which CRH and NPPA are the two key drug targets of LXNX formula. Further evidences from Chinese herb pharmacological databases indicate that Pinellia ternata (Banxia) has relatively strong adjustive functions on the two key targets.

We demonstrated a 100 TW-class femtosecond Ti: sapphire laser running at repetition rate of 0.1 Hz by adding a stage amplifier in the 20 TW/10 Hz laser facility (XL-II). Pumping the new stage amplifier with the 25 J green Nd:glass laser, we successfully upgraded the laser energy to 3.4 J with duration of 29 fs, corresponding to a peak power of 117 TW.

Abstract Background Carcinoma of unknown primary site (CUP) has a poor prognosis and the prognostic factors in these patients are not well established. Furthermore, there are no selection criteria for patients who should benefit from chemotherapy. Methods The medical records of 179 CUP patients who were treated at Taipei Veterans General Hospital from 2000 to 2009 were reviewed. Factors associated with survival were determined by Kaplan-Meier analysis. Differences between the groups with and without palliative chemotherapy were analyzed. Results Univariate analysis revealed multiple prognostic factors, including performance status, lung metastasis, number of metastatic organs, serum albumin, corrected serum calcium, lactate dehydrogenase (LDH), sodium, and cholesterol levels, palliative chemotherapy, and white blood cell and lymphocyte counts. Multivariate analysis showed that performance status < 2, serum albumin level ≥ 3.5 g/dl, corrected serum calcium level < 10.7 mg/dl, single metastatic organ, and palliative chemotherapy were independent factors of better prognosis. Patients with better performance status, higher serum albumin, and lower serum LDH levels had significantly greater benefit from palliative chemotherapy. Conclusions Certain patients with unfavorable CUP will have better survival. Identification of patients with unfavorable CUP who could benefit from palliative chemotherapy warrants future prospective studies.

Research on novel ultrafast photonic devices with wide adaptability has become important scientific technical means to realize both scheme innovation and performance breakthrough in fiber laser generation. As types of transition metal oxide, manganese dioxide (MnO2) materials exhibit remarkable properties including high photothermal stability, strong oxidation resistance, and excellent optical properties, making them promising candidate for utilization as modulation devices in nonlinear optics and ultrafast optics fields. We investigate the impact of MnO2-based saturable absorber (SA) on the pulse characteristics. The experiment reveals that MnO2-based SA supports effectively pulsed laser generation in wide pump power range and large dispersion parameter space with signal-to-noise ratio more than 85 dB. As far as we know, the pump power response range is outstanding among the most of the reported pulsed lasers, which is attributed to the large modulation depth of MnO2 SA. We also investigate the impact of dispersion on the characteristics of laser output, which is not involved in other similar works. This research indicates that MnO2 as a photonic device has vast potential in advanced ultrafast optics. [ABSTRACT FROM AUTHOR]

Hydrogels can form physically or chemically interactions with tissues and are widely used in the design of bioadhesive material. Polydopamine (PDA)/polyacrylamide (PAM)‐based adhesion hydrogels have emerged as one of the hydrogel adhesive materials with great potential for development. However, this type of hydrogel has low mechanical and adhesion properties, which has certain limitations in practical applications. Herein, inspired by the mussel adhesion mechanism, we introduced PDA into PAM/3‐aminophenylboronic acid grafted sodium alginate (SA‐PBA) double network system prepared a series of adhesive hydrogels, PDA was crosslinked by dynamic boronic ester bonds with SA‐PBA. The experimental results established that the hydrogels have favorable adhesive, anti‐fatigue, stretchable, and self‐healing properties. Cytocompatibility assay and in vitro hemolysis assay also indicated that the multifunctional hydrogel has excellent cytocompatibility and hemocompatibility. [ABSTRACT FROM AUTHOR]

Rational construction of oxygen vacancies in electrode materials can effectively enhance the comprehensive sodium storage performance of the material. However, how to precisely control and regulate the oxygen vacancies concentration remains to be investigated, and the impact on electrochemical performance is still unclear. Herein, TiO2 nanoparticles with tunable oxygen vacancies concentrations are used as research models, which were fabricated through a simple and effective plasma method. The experimental results reveal that a moderate concentration of oxygen vacancies can significantly improve the electrochemical kinetics and charge conductivity of the TiO2 electrodes. In addition, oxygen vacancies promote the release of fluorine from the fluoroethylene carbonate (FEC) in the electrolyte, inducing a NaF‐rich solid electrolyte interphase, thus ensuring interfacial stability and inhibiting excessive electrolyte decomposition. Consequently, the well‐designed anode exhibits outstanding rate capability (147 mAh g−1 at 5 A g−1) and extremely stable cycling performance (nearly 100 %, 3000 cycles). This work provides a feasible method for realizing defect concentration modulation in energy storage materials and offers new insights into interfacial chemistry for improving battery performance. [ABSTRACT FROM AUTHOR]

Patients with microsatellite instability‐high (MSI‐H) colorectal cancer (CRC) have high tumor mutation burden and tumor immunogenicity, exhibiting a higher response rate to immunotherapy and better survival. However, a portion of MSI‐H CRC patients still experience adverse disease outcomes. We aimed to identify the tumor‐autonomous regulators determining these heterogeneous clinical outcomes. The Cancer Genome Atlas (TCGA) dataset was used to identify regulators in MSI‐H CRC patients with unfavorable outcomes. Stable CRC tumor clones expressing targeted regulators were established to evaluate migratory and stemness properties, immune cell vulnerability, and cell‐in‐cell (CIC) structure formation. RNA‐sequencing (RNA‐seq) was used to identify enriched biological pathways in stable CRC tumor clones. Clinicopathological characterization of formalin‐fixed paraffin‐embedded (FFPE) MSI‐H CRC specimens was performed to explore the underlying mechanisms involved. We showed that cancer/testis antigen family 45 member A1 (CT45A1) expression was upregulated in MSI‐H CRC patients with poor survival outcomes. CT45A1‐expressing microsatellite stable (MSS) CRC cells showed enhanced migratory ability. However, CT45A1‐expressing MSI‐H CRC cells, but not MSS CRC cells, showed higher resistance to natural killer (NK) cell cytotoxicity and served as outer cells in homotypic CIC structures, preventing exogenous or therapeutic antibody access to inner CRC cells. Inactivating RHO‐ROCK/MLCK‐MLC2 signaling with small‐molecule inhibitors or short‐hairpin RNAs (shRNAs) targeting myosin light chain kinase (MYLK) abolished NK cell resistance and reduced the outer cell fate of CT45A1‐expressing MSI‐H CRC cells. In MSI‐H CRC patients, CT45A1‐positive tumors exhibited increased MLC2 phosphorylation, increased outer cell fate, and decreased survival. We demonstrated that CT45A1 potentiates the advanced progression of MSI‐H CRC, and targeting MLC2 phosphorylation may enhance immunotherapy efficacy in CT45A1‐positive MSI‐H CRC patients. [ABSTRACT FROM AUTHOR]