REMEDIAL APPLICATIONS OF SILENCING RIBONUCLEIC ACIDS AND MODALITIES FOR ITS DELIVERY TO THE KIDNEYS - A REVIEW

Background: The Kidney has been the target organ for the delivery of silencing ribonucleic acids (silencing RNA) administered systemically in comparison to other body tissues. Materials and method: In this review, we discussed different approaches made to delivering proteins to the kidneys in different conditions like normal and pathological defects. Data from clinical experiments have been used to discuss and support the administration of silencing RNA for the treatment of kidney diseases. Results: Results were achieved using the available genome wide RNA libraries. Conclusion: The research results are helpful in application to 3D and conventional models to find the involvement of signal pathways in kidney diseases

Sarcopenia Was a Poor Prognostic Predictor for Patients With Advanced Lung Cancer Treated With Immune Checkpoint Inhibitors

BackgroundIt remains not well known whether skeletal muscle mass (SMM) loss has any impact on the effectiveness of immune checkpoint inhibitors (ICIs) in patients with advanced lung cancer. We aimed to evaluate the association between SMM and clinical outcome of patients with advanced lung cancer receiving ICIs as first line or second line.Materials and MethodsFrom March 1st, 2019 to March 31st, 2021 at our hospital, 34 patients with advanced lung cancer treated with first-line or second-line ICIs were enrolled retrospectively. The estimation of skeletal muscle index (SMI) for sarcopenia was assessed at the level of the third lumbar vertebra (L3) on computed tomography (CT) images obtained within 4 weeks before initiation of ICIs treatment. The impact of sarcopenia (low SMI) on progression free survival (PFS) was analyzed using Kaplan-Meier method and log-rank tests. The effect of various variables on PFS was evaluated using Cox proportional hazards regression model with univariate and multivariate analysis. The impact on treatment response including objective response rate (ORR) and disease control rate (DCR) and immunotherapy related adverse events (irAEs) between patients with and without sarcopenia was compared by the chi-squared test. The comparison of SMI value between patients with objective response (OR), disease control (DC) and those without OR and DC was used student t-test or Mann-Whitney U test.ResultsBoth in univariate and multivariate analysis, sarcopenia and treatment lines were the predictive factors for PFS (p < 0.05). Patients with sarcopenia had significantly shorter PFS than that of non-sarcopenic ones [6.57 vs. 16.2 months, hazard ratios (HR) = 2.947 and 3.542, and 95% confidence interval (CI): 1.123–13.183 and 1.11–11.308, p = 0.022 and 0.033]. No significant difference in ORR and irAEs was found. Patients with sarcopenia had lower DCR than those without sarcopenia. The mean SMI value of DCR group and non-DCR group was 32.94 ± 5.49 and 44.77 ± 9.06 cm2/m2, respectively (p = 0.008).ConclusionSarcopenia before immunotherapy might be a significant predictor for poor prognosis including shorter PFS and lower DCR in patients with advanced lung cancer treated with ICIs as first line or second line

Pyrrolidine Dithiocarbamate (PDTC) Attenuates Cancer Cachexia by Affecting Muscle Atrophy and Fat Lipolysis

Cancer cachexia is a kind of whole body metabolic disorder syndrome accompanied with severe wasting of muscle and adipose tissue. NF-κB signaling plays an important role during skeletal muscle atrophy and fat lipolysis. As an inhibitor of NF-κB signaling, Pyrrolidine dithiocarbamate (PDTC) was reported to relieve cancer cachexia; however, its mechanism remains largely unknown. In our study, we showed that PDTC attenuated cancer cachexia symptom in C26 tumor bearing mice models in vivo without influencing tumor volume. What’s more, PDTC inhibited muscle atrophy and lipolysis in cells models in vitro induced by TNFα and C26 tumor medium. PDTC suppressed atrophy of myotubes differentiated from C2C12 by reducing MyoD and upregulating MuRF1, and preserving the expression of perilipin as well as blocking the activation of HSL in 3T3-L1 mature adipocytes. Meaningfully, we observed that PDTC also inhibited p38 MAPK signaling besides the NF-κB signaling in cancer cachexia in vitro models. In addition, PDTC also influenced the protein synthesis of skeletal muscle by activating AKT signaling and regulated fat energy metabolism by inhibiting AMPK signaling. Therefore, PDTC primarily influenced different pathways in different tissues. The study not only established a simple and reliable screening drugs model of cancer cachexia in vitro but also provided new theoretical basis for future treatment of cancer cachexia

A Facile Method to Prepare Superhydrophobic Coatings for Various Substrates

In this study, the superhydrophobic composite coatings for self-cleaning were fabricated by mixing fluorine resin and two kinds of nanoparticles of carbon nanotubes (CNTs) and SiO2. When the mass ratio of CNTs to SiO2 is 2:3 and the added amount of nanoparticles is 75 wt. %, the superhydrophobic composite coatings with a water contact angle of 156.8° show the best self-cleaning property and 3.6° of contact angle hysteresis. Furthermore, the superhydrophobic composite coatings demonstrate good properties such as chemical resistance, thermal stability, and mechanical stability. The superhydrophobic composite coatings could be used for oil/water separation and could be applied to various substrate surfaces such as glass plates, cloth, board, steel plate, PVC plate, and so on. The superhydrophobic composite coatings show practical value in many fields because of their low cost and large area preparation

A Facile Method to Prepare Superhydrophobic Coatings for Various Substrates

In this study, the superhydrophobic composite coatings for self-cleaning were fabricated by mixing fluorine resin and two kinds of nanoparticles of carbon nanotubes (CNTs) and SiO2. When the mass ratio of CNTs to SiO2 is 2:3 and the added amount of nanoparticles is 75 wt. %, the superhydrophobic composite coatings with a water contact angle of 156.8° show the best self-cleaning property and 3.6° of contact angle hysteresis. Furthermore, the superhydrophobic composite coatings demonstrate good properties such as chemical resistance, thermal stability, and mechanical stability. The superhydrophobic composite coatings could be used for oil/water separation and could be applied to various substrate surfaces such as glass plates, cloth, board, steel plate, PVC plate, and so on. The superhydrophobic composite coatings show practical value in many fields because of their low cost and large area preparation

Wind-Induced Vibration Analysis of a Pentagonal Three–Four Strut Hybrid Open-Type Cable Dome

Previous research has confirmed that the newly proposed pentagonal three–four strut hybrid cable dome exhibits superior static performance compared to traditional cable domes, though its dynamic characteristics still require further study. Cable domes are wind-sensitive structures, and the results of a wind-induced vibration analysis are beneficial for the selection and construction of cable domes. In this study, a finite element model of a new open-type cable dome with a span of 120 m is established. The MATLAB 2017a programming language is employed to simulate pulsating winds, followed by a nonlinear dynamic analysis to analyze the wind-induced vibrations of the structure. The reliability of the pulsating wind model is confirmed by comparing the simulated spectrum with the target spectrum. Moreover, a wind-induced vibration time history analysis is performed to obtain the node displacement and internal force of components wind vibration coefficients, aiding in the approximation of pulsating winds with average winds in a wind-resistant design. Furthermore, a parametric analysis is carried out, ranking nodes and components based on sensitivity. The result shows that the structure exhibits the strongest wind resistance when the rise–span ratio is f/l=0.07 and the thickness–span ratio is h/l=0.08. Notably, the outer upper chord node, 2a, and the inner lower chord hoop cable, H1, are identified as the most sensitive node and component within the structure, respectively. Overall, the structure demonstrates excellent wind resistance performance, and the maximum wind vibration coefficient value remains below 3

Comparative analysis of αB-crystallin expression in heat-stressed myocardial cells in vivo and in vitro.

Relationships between αB-crystallin expression patterns and pathological changes of myocardial cells after heat stress were examined in vitro and in vivo in this study using the H9C2 cell line and Sprague-Dawley rats, respectively. Histopathological lesions, characterized by acute degeneration, karyopyknosis and loss of a defined nucleus, became more severe in rat hearts over the course of heat stress treatment from 20 min to 100 min. The expression of αB-crystallin in rat hearts showed a significant decrease (P<0.05) throughout the heat stress treatment period, except at the 40 min time point. Likewise, decreased αB-crystallin expression was also observed in the H9C2 cell line exposed to a high temperature in vitro, although its expression recovered to normal levels at later time points (80 and 100 min) and the cellular damage was less severe. The results suggest that αB-crystallin is mobilized early after exposure to a high temperature to interact with damaged proteins but that the myocardial cells cannot produce sufficient αB-crystallin for protection against heat stress. Lower αB-crystallin expression levels were accompanied by obvious cell/tissue damage, suggesting that the abundance of this protein is associated with protective effects in myocardial cells in vitro and in vivo. Thus, αB-crystallin is a potential biomarker of heat stress

Identification of sex determination locus and development of marker combination in Vitis based on genotyping by target sequencing

The grapevine is an important and economically valuable fruit crop, with flower sex being a key genetic trait that directly affects grapevine yield and quality. Despite its significance, there is a lack of studies on sex-linked molecular markers that can assist in grapevine breeding. In this study, we developed a grapevine single nucleotide polymorphism (SNP) marker array using a combination of genotyping by target sequencing (GBTS) and capture-in-solution technology and applied it to marker-assisted selection (MAS) of grapevine gender. The SNP array could detect a total of 20,597 core SNPs and 97,453 multiple SNPs (mSNPs), covering over 99% of the grapevine genome on each chromosome. A total of 131 progenies from a cross between Vitis vinifera 'Cabernet Sauvignon' and Vitis pseudoreticulata 'Huadong1058' that exhibited segregated sex phenotypes were sequenced using this array. Through locus mapping and a genome-wide association study (GWAS), a locus on chromosome 2 (54.74−58.80 cM) that explained 98.6% of the phenotypic variation was identified. To further utilize this locus, a sex prediction marker combination consisting of two SNPs was developed, which accurately predicted the sex of 34 natural grapevine varieties/accessions. This study demonstrates the application of GBTS in grapevine breeding and provides a reliable MAS marker set for early-stage sex selection