Endothelium-Derived Engineered Extracellular Vesicles Protect the Pulmonary Endothelial Barrier in Acute Lung Injury.

Acute lung injury (ALI) is a severe respiratory disease with a high mortality rate. The integrity of the pulmonary endothelial barrier influences the development and prognosis of ALI. Therefore, it has become an important target for ALI treatment. Extracellular vesicles (EVs) are promising nanotherapeutic agents against ALI. Herein, endothelium-derived engineered extracellular vesicles (eEVs) that deliver microRNA-125b-5p (miRNA-125b) to lung tissues exerting a protective effect on endothelial barrier integrity are reported. eEVs that are modified with lung microvascular endothelial cell-targeting peptides (LET) exhibit a prolonged retention time in lung tissues and targeted lung microvascular endothelial cells in vivo and in vitro. To improve the efficacy of the EVs, miRNA-125b is loaded into EVs. Finally, LET-EVs-miRNA-125b is constructed. The results show that compared to the EVs, miRNA-125b, and EVs-miRNA-125b, LET-EVs-miRNA-125b exhibit the most significant treatment efficacy in ALI. Moreover, LET-EVs-miRNA-125b is found to have an important protective effect on endothelial barrier integrity by inhibiting cell apoptosis, promoting angiogenesis, and protecting intercellular junctions. Sequencing analysis reveals that LET-EVs-miRNA-125b downregulates early growth response-1 (EGR1) levels, which may be a potential mechanism of action. Taken together, these findings suggest that LET-EVs-miRNA-125b can treat ALI by protecting the endothelial barrier integrity.

In Vitro Affinity Maturation of Nanobodies against Mpox Virus A29 Protein Based on Computer-Aided Design.

Mpox virus (MPXV), the most pathogenic zoonotic orthopoxvirus, caused worldwide concern during the SARS-CoV-2 epidemic. Growing evidence suggests that the MPXV surface protein A29 could be a specific diagnostic marker for immunological detection. In this study, a fully synthetic phage display library was screened, revealing two nanobodies (A1 and H8) that specifically recognize A29. Subsequently, an in vitro affinity maturation strategy based on computer-aided design was proposed by building and docking the A29 and A1 three-dimensional structures. Ligand-receptor binding and molecular dynamics simulations were performed to predict binding modes and key residues. Three mutant antibodies were predicted using the platform, increasing the affinity by approximately 10-fold compared with the parental form. These results will facilitate the application of computers in antibody optimization and reduce the cost of antibody development; moreover, the predicted antibodies provide a reference for establishing an immunological response against MPXV.

Finding appropriate nickel-titanium instruments for lingual canals in mandibular first premolars with two canals: A micro-CT study.

This study aimed to find appropriate nickel-titanium instruments for lingual canals in mandibular first premolars with two canals. Forty-two extracted mandibular first premolars with lingual canals (Vertucci type V) verified by micro-CT scanning were selected. The teeth were randomly divided into three groups, and their lingual canals were instrumented by M3, HyFlex CM and XP-endo Shaper, respectively. After instrumentation, the canal morphology was scanned again by micro-CT. The canal morphologies of pre- and post-instrumentation were reconstructed and aligned. Morphological changes of the lingual canals were evaluated. No instrument breakages occurred during the procedure of root canal instrumentation. HyFlex CM and XP-endo Shaper performed better than M3 files in preparation of lingual canals (Vertucci type V) of mandibular first premolars in terms of apical transportation and unprepared surface area.

Two unusual novel iridoid glycosides from Cornus officinalis fruit and their biological activities.

Two unusual novel iridoid glycosides, cornsecoside A (1) and cornsecoside B (2), were isolated from a 40% ethanol elution fraction of a 50% ethanol extract of Cornus officinalis fruit. Their structures were determined by spectroscopic data analysis combined with hydrolysis and ECD spectroscopy. In addition, compounds 1 and 2 exhibited cytotoxic activity against Bel-7402 cells with IC50 values of 8.12 and 9.31 µM, and were neuroprotective against H2O2-induced SH-SY5Y cell injure at a concentration of 10 µM.

Factors affecting the outcome of full pulpotomy in permanent posterior teeth diagnosed with reversible or irreversible pulpitis.

This study aimed to investigate the factors affecting the success rate of full pulpotomy in permanent posterior teeth with pulpitis. The study included 105 permanent posterior teeth clinically diagnosed as reversible or irreversible pulpitis in 92 patients aged 18-82 years. All teeth underwent a full pulpotomy using mineral trioxide aggregate as a capping material and were recalled for clinical and radiographic evaluation at 3, 6, 12, and 24 months postoperatively. The overall success rate after the 12-month review was above 90%, and failed cases mainly occurred during the first 12 months after treatment. In this study, the treatment outcome of pulpotomy was not related to sex, or tooth position and the cause of pulpitis. To analyze the influence of age on the treatment outcome, all the teeth were allocated to three groups: group 1 (18-39 years); group 2 (40-59 years); and group 3 (≥ 60 years). A significant difference in success rate was found between groups 1 and 3 (P = 0.014). These results suggest that pulpotomy can be used as an alternative treatment for permanent mature teeth diagnosed with pulpitis and that aging is one factor affecting the treatment outcome.

Imaging Findings of Mammary Myofibroblastoma: A Rare Fat-Containing Entity.

ABSTRACT: Mammary myofibroblastoma (MFB) is a rare benign stromal neoplasm; its imaging features are rarely reported and nonspecific. We retrospectively analyzed a case of pathologically proved breast MFB that revealed indistinct high-density mass in mammography and hypoechoic ill-defined breast tumor in ultrasonography. Meanwhile, hypointense appearance on T2-weighted imaging of magnetic resonance imaging and containing fat tissue might be very valuable characteristics in the differential diagnosis of breast MFB.

The Vigabatrin Induced Retinal Toxicity is Associated with Photopic Exposure and Taurine Deficiency: An In Vivo Study.

BACKGROUND/AIMS: Retinal toxicity is one of the most commonly discussed and concerning adverse effects of vigabatrin (VGB). The present study explored the relationship between the VGB elicited retinal toxicity, photopic exposure, and taurine deficiency, aiming at screening for risk factors to minimize the adverse effects of VGB. METHODS: The effects of VGB on function and morphology of mouse retinas were examined via a series of in vivo tests, including electroretinography (ERG), Spectral domain optical coherence tomography (SD-OCT), and optokinetic testing. Moreover, VGB-treated mice were in addition treated with taurine to verify possible protective effects against retinal toxicity. RESULTS: A close relationship between VGB induced retinal toxicity and light exposure was observed. The VGB-treated mice which were reared in darkness preserved better visual function and retinal architectures as verified by the optokinetic tests, OCT and ERG examinations. The retinal taurine level of the VBG-treated mice which were exposed to light were significantly lower than that of the VBG mice reared in darkness. Furthermore, several in vivo evidence provided by our research confirmed that the VGB induced morphological and functional impairments could be partially alleviated by taurine treatment. The present study showed the retinal toxicity of VGB by in vivo measurements. CONCLUSION: The VGB induced retinal toxicity is closely associated with photopic exposure and taurine deficiency. Patients who are taking VGB might benefit from minimization of light exposure and dietetic taurine supplements.

[HPLC Characteristic Fingerprint of "Boju" Chrysanthemum morifolium].

OBJECTIVE: To provide a scientific basis for quality control of "Boju" Chrysanthemum morifolium by establishing a HPLC characteristic fingerprint. METHODS: The HPLC analysis was performed on a Spursil C18 chromatographic column (250 mm x 4. 6 mm, 5 µm), and the mobile phase was acetonitrile-0. 1% phosphoric acid in a gradient mode with the flow rate of 1. 0 mL/min. The detection wavelength was 325 nm and the temperature of column was 30 °C. RESULTS: The common pattern of HPLC characteristic chromatographic profile was established. There were 16 common peaks, five of which were identified in the pattern. The similarities of 10 batches of "Boju" Chrysanthemum monrfolium were evaluated, and all of them were greater than 0. 900. CONCLUSION: This analysis method of HPLC characteristic chromatographic fingerprint is simple and reproducible, and it can provide a scientific basis for identification and quality evaluation of "Boju" Chrysanthemum monfolium.

[Determination of Trace Elements in Different Parts of Boju and Root Soil by ICP-MS].

OBJECTIVE: To explore the contents and enrichment status of the trace elements in Boju by using ICP-MS. METHODS: Trace elements of the different parts of Boju and the soil near the roots were determined by microwave digestion-ICP-MS and the correlation of the data obtained was tested by using the statistical software. RESULTS: There were differences among the contents of the eight elements in the different parts of Boju and the soil; there were obvious differences in the enrichment factor of eight elements in the different parts of Boju, which ranged from 0.0054 to 0.9205; there was a significant positive correlation between Fe and Mg in the inflorescence and the contents of Fe was positively correlated with the soil; for Al, Ba and Mg, there were significant positive correlations between its soil contents and leaves contents. CONCLUSION: Boju absorbs the inorganic elements selectively,the yield and quality of Chinese medicinal materials can be improved by improving the cultivation.

[Experiences of Professor Zhou Zhong-ying in diagnosing and treating rheumatoid arthritis by data mining].

OBJECTIVE: To summarize Professor ZHOU Zhong-ying's academic ideas and clinical experiences in diagnosing and treating rheumatoid arthritis (RA). METHODS: Totally 153 clinical case reports were recruited. Data mining techniques like frequencies, factor analysis, and association analysis were used in order to find out laws of syndrome, pathogenesis, treatment methods, formulae and medication. RESULTS: By statistical analyses, we found 14 main symptoms, 76 commonly used clinical drugs, 8 core prescriptions for RA, and the correlation between main pathogeneses and related drugs. CONCLUSION: Results analyzed and summarized from mining his experiences in RA treatment were in line with clinical practice.