Chitin deacetylase (CDA) can accelerate the conversion of chitin to chitosan, influencing the mechanical properties and permeability of the cuticle structures and the peritrophic membrane (PM) in ...insects. Putative Group V CDAs SeCDA6/7/8/9 (SeCDAs) were identified and characterized from beet armyworm
larvae. The cDNAs of
contained open reading frames of 1164 bp, 1137 bp, 1158 bp and 1152 bp, respectively. The deduced protein sequences showed that SeCDAs are synthesized as preproteins of 387, 378, 385 and 383 amino acid residues, respectively. It was revealed via spatiotemporal expression analysis that
were more abundant in the anterior region of the midgut. The
were down-regulated after treatment with 20-hydroxyecdysone (20E). After treatment with a juvenile hormone analog (JHA), the expression of
and
was down-regulated; in contrast, the expression of
and
was up-regulated. After silencing
(the conserved sequences of Group V CDAs) via RNA interference (RNAi), the layer of intestinal wall cells in the midgut became more compact and more evenly distributed. The vesicles in the midgut were small and more fragmented or disappeared after
were silenced. Additionally, the PM structure was scarce, and the chitin microfilament structure was loose and chaotic. It was indicated in all of the above results that Group V CDAs are essential for the growth and structuring of the intestinal wall cell layer in the midgut of
. Additionally, the midgut tissue and the PM structure and composition were affected by Group V CDAs.
At present, there is no effective noninvasive method for the accurate diagnosis of early‐stage lung adenocarcinoma (LUAD). This study examined the profile of plasma extracellular vesicle ...(EV)‐delivered microRNAs (miRNAs) in patients with invasive stage I LUAD. In this study, a total of 460 participants were enrolled, including 254 patients with LUAD, 76 patients with benign pulmonary nodules (BPNs), and 130 healthy control patients (HCs). miRNA sequencing was used to analyze the EV miRNA profile of the patient plasma samples (n = 150). A diagnostic signature (d‐signature) was identified by applying a stepwise logistic regression algorithm, and a single‐center training cohort (n = 150) was tested, followed by a multicenter validation cohort (n = 100). A d‐signature comprising four EV‐derived miRNAs (hsa‐miR‐106b‐3p, hsa‐miR‐125a‐5p, hsa‐miR‐3615, and hsa‐miR‐450b‐5p) was developed for the early detection of LUAD. The d‐signature had high precision with area under the curve (AUC) values of 0.917 and 0.902 in the training and test cohorts, respectively. Moreover, the d‐signature could recognize patients with adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) with AUC values of 0.846 and 0.92, respectively. To sum up, our study detailed the plasma EV–derived miRNA profile in early LUAD patients and developed an EV‐derived miRNA d‐signature to detect early LUAD.
This study provides the largest genome‐wide analysis of extracellular vesicle (EV) microRNA (miRNA) in plasma from early lung adenocarcinoma (LUAD) patients, suggesting the feasibility of identifying cancer biomarkers based on EV miRNA profiling. We developed an EV miRNA–based diagnostic signature (d‐signature) that showed high accuracy for the diagnosis of early LUAD based on multicentric validation. The d‐signature was able to detect adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) as readily as invasive stage I invasive adenocarcinoma (IAC).
Rituximab/chemotherapy relapsed and refractory B cell lymphoma patients have a poor overall prognosis, and it is urgent to develop novel drugs for improving the therapy outcomes. Here, we examined ...the therapeutic effects of chidamide, a new histone deacetylase (HDAC) inhibitor, on the cell and mouse models of rituximab/chemotherapy resistant B-cell lymphoma. In Raji-4RH/RL-4RH cells, the rituximab/chemotherapy resistant B-cell lymphoma cell lines (RRCL), chidamide treatment induced growth inhibition and G0/G1 cell cycle arrest. The primary B-cell lymphoma cells from Rituximab/chemotherapy relapsed patients were sensitive to chidamide. Interestingly, chidamide triggered the cell death with the activation of autophagy in RRCLs, likely due to the lack of the pro-apoptotic proteins. Based on the RNA-seq and chromatin immunoprecipitation (ChIP) analysis, we identified BTG1 and FOXO1 as chidamide target genes, which control the autophagy and the cell cycle, respectively. Moreover, the combination of chidamide with the chemotherapy drug cisplatin increased growth inhibition on the RRCL in a synergistic manner, and significantly reduced the tumor burden of a mouse lymphoma model established with engraftment of RRCL. Taken together, these results provide a theoretic and mechanistic basis for further evaluation of the chidamide-based treatment in rituximab/chemotherapy relapsed and refractory B-cell lymphoma patients.
Background
The present study aimed at comparing the success rate and safety of proximal versus distal approach for ultrasound (US)-guided axillary vein catheterization (AVC) in cardiac surgery ...patients susceptible to bleeding.
Methods
In this single-center randomized controlled trial, cardiac surgery patients susceptible to bleeding and requiring AVC were randomized to either the proximal or distal approach group for US-guided AVC. Patients susceptible to bleeding were defined as those who received oral antiplatelet drugs or anticoagulants for at least 3 days. Success rate, catheterization time, number of attempts, and mechanical complications within 24 h were recorded for each procedure.
Results
A total of 198 patients underwent randomization: 99 patients each to the proximal and distal groups. The proximal group had the higher first puncture success rate (75.8% vs. 51.5%,
p
< 0.001) and site success rate (93.9% vs. 83.8%,
p
= 0.04) than the distal group. However, the overall success rates between the two groups were similar (99.0% vs. 99.0%;
p
= 1.00). Moreover, the proximal group had fewer average number of attempts (
p
< 0.01), less access time (
p
< 0.001), and less successful cannulation time (
p
< 0.001). There was no significant difference in complications between the two groups, such as major bleeding, minor bleeding, arterial puncture, pneumothorax, nerve injuries, and catheter misplacements.
Conclusions
For cardiac surgery patients susceptible to bleeding, both proximal and distal approaches for US-guided AVC can be considered as feasible and safe methods of central venous cannulation. In terms of the first puncture success rate and cannulation time, the proximal approach is superior to the distal approach.
Trial registration
Clinicaltrials.gov, NCT03395691. Registered January 10, 2018,
https://clinicaltrials.gov/ct2/show/NCT03395691?cond=NCT03395691&draw=1&rank=1
.
Biomorphic ceramic materials have potential high-temperature applications, owing to their low density, good corrosion resistance and excellent shape capability, but achieving both high specific ...strength and excellent thermal oxidation resistance is challenging. In this report, shaddock peel-derived C–SiC–SiO2 composites were successfully prepared by the polymer precursor infiltration (PPI) technique with an optimized heating program. The composites prepared at 1600 °C exhibit the highest compressive strength (∼14.0 MPa) and specific strength (∼1.5 × 107 N m/kg), while those sintered at 1200 °C exhibit the highest bending strength (∼27.4 MPa). The composites exhibit good thermal oxidation resistance (up to 1400 °C) with a low weight loss ratio (<0.11 g/cm3), moreover, the compressive strength of the composites sintered at 1200 °C after thermal oxidation at 1400 °C surprisingly increased from 11.6 ± 2.7 MPa to 21.5 ± 3.5 MPa. The PPI technique provides a viable route to introduce Si source into natural materials and the shaddock peel-derived C–SiC–SiO2 composites are light materials with high strength and excellent high-temperature thermal oxidation resistance.
The development of novel nanoparticles as a new generation therapeutic drug platform is an active field of chemistry and cancer research. In recent years, fullerene nanoparticles have received ...extensive attention due to their unique physical and chemical properties. Properly modified fullerene nanoparticles have excellent biocompatibility and significant anti-tumor activity, which makes them have broad application prospects in the field of cancer therapy. Therefore, understanding the anti-tumor mechanism of fullerene nanoparticles is of great significance for the design and development of anti-tumor drugs with low toxicity and high targeting. This review has focused on various anti-tumor mechanisms of fullerene derivatives and discusses their toxicity and their distribution in organisms. Finally, the review points out some urgent problems that need solution before fullerene derivatives as a new generation of anti-tumor nano-drug platform enter clinical research.
Pancreatic cancer (PC) is a fatal disease that has a poor 5-year survival rate. The poor prognosis can be attributed to both troublesome detections at the initial stage, which makes the majority of ...the treatment options largely unsuccessful and leads to extensive metastasis, as well as to its distinct pathophysiological characteristics, such as rich desmoplastic tumours bounded by dysplastic and hypo perfused vessels restricting the mobility of therapeutic agents. Continued attempts have been made to utilise innovative measures for battling PC to increase the therapeutic effectiveness of therapies and overcome their cytotoxicity. Combined cancer targeting and gene silencing approach has shown improved outcomes in patients' survival rates and quality of life, offering a potential solution to therapeutic complications. It particularly targets various barriers to alleviate delivery problems and diminish tumour recurrence and metastasis. While aptamers, a type of single-stranded nucleic acids with strong binding affinity and specificity to target molecules, have recently surfaced as a viable PC strategy, siRNA can interfere with the expression of certain genes. By concurrently suppressing genes and boosting targeted approach, the cocktail of siRNA/Aptamer and other therapeutic drugs can circumvent the multi-drug resistance phenomena. Additionally, combination therapy with additive or synergistic effects can considerably increase the therapeutic efficacy of anti-cancer medications. This study outlines the primary difficulties in treating PC, along with recent developments in siRNA/Aptamer mediated drug delivery to solve the major hiccup of oncology field.
Ewing sarcoma (ES) is sensitive to systemic therapy, including chemotherapy and anti-angiogenesis Tyrosine Kinase Inhibitors(aaTKIs). However, the prognosis of patients with metastatic disease ...remains poor. Recurrence or distant metastasis after a complete response (CR) or near-CR due to systemic therapy is not rare.
We reviewed data from 187 ES patients between 2014-2019 treated at a single institute in China. Patients with extensive lung/pleural metastases (L/Pmeta) who had a CR or near-CR after first- or second-line chemotherapy with or without aaTKIs were retrospectively enrolled. Event-free survival (EFS) and overall survival (OS) were determined using the Kaplan-Meier method. For patients who had L/P recurrence, images were reviewed to define the exact location of each recurrent lesion, compared with the primary L/P lesion before chemotherapy and summarized as the relapse pattern.
Seventeen patients and 21 cases of CR/nCR (5 by VDC/IE, 3 by VIT, and 13 by AVI) were finally analyzed. Median follow-up for surviving patients was 39.6 (range, 14.5-60.9) months. Median EFS and OS were 9.3 (95% confidence interval CI, 2.0-16.6) months and 37.5 (95% CI, 21.8-53.1) months, respectively. The 2-year EFS was 19% and the 2-year OS was 70.6%, respectively. Most patients (82.4%) received whole lung irradiation (WLI). Lung/pleural relapse occurred in 71.4% (15/21) of CR/nCR cases. Most notably, all recurrent lesions exactly coincided with the original metastatic lesions before chemotherapy (exactly in situ) in 9 of the 15 recurrent cases, which was thus the major relapse pattern, whereas 42.9% had distant metastases other than L/Pmeta.
Survival of ES patients with extensive L/Pmeta remains poor, even if they have a CR after systemic therapy. Recurrence exactly in situ is the major relapse pattern. WLI is not sufficient to prevent local recurrence in lung or pleura. More aggressive local treatment for metastatic lesions is warranted.
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