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The change of symptom burden increased initially and then declined at T2-T5. The change of hope remained steady between T1 and T5. The change of symptom burden and hope significantly predicted the change of QOL over time.

Clinicians are suggested to assess symptom burden and hope regularly in HNC during their CCRT and, if needed, promptly provide interprofessional care in time. Reducing symptom burden and maintaining a mindful hope could improve QoL in HNC survivors during CCRT.

Clinicians are suggested to assess symptom burden and hope regularly in HNC during their CCRT and, if needed, promptly provide interprofessional care in time. Reducing symptom burden and maintaining a mindful hope could improve QoL in HNC survivors during CCRT.

Days spent at home (DASH) near the end of life is considered an important patient-centered goal and outcome because many patients want to stay at home toward the end of life. This study aimed to estimate the individual DASH near the end of life and identify its early predictors, including muscle mass and physical function, among elderly patients with advanced non-small-cell lung cancer (NSCLC).

We conducted a post hoc analysis of the prospective observational study (UMIN000009768) that recruited patients aged ≥ 70 years who were scheduled to undergo first-line chemotherapy because of advanced NSCLC. We measured the muscle mass by bioelectrical impedance analysis at baseline. DASH was calculated as 30 days minus the number of days spent in hospitals, palliative care facilities, or nursing homes during the last 30 days of life. We performed linear regression analyses to evaluate the predictors of DASH.

Altogether, 16 women and 28 men with a median overall survival of 15.5 months (range 2.9-58.9) were inclC. Our findings would encourage early discussions about end-of-life care for patients with advanced cancers with risk factors for short DASH at the time of diagnosis, and thus, improve the quality of end-of-life care.The unscented transform uses a weighted set of samples called sigma points to propagate the means and covariances of nonlinear transformations of random variables. However, unscented transforms developed using either the Gaussian assumption or a minimum set of sigma points typically fall short when the random variable is not Gaussian distributed and the nonlinearities are substantial. In this paper, we develop the generalized unscented transform (GenUT), which uses adaptable sigma points that can be positively constrained, and accurately approximates the mean, covariance, and skewness of an independent random vector of most probability distributions, while being able to partially approximate the kurtosis. For correlated random vectors, the GenUT can accurately approximate the mean and covariance. In addition to its superior accuracy in propagating means and covariances, the GenUT uses the same order of calculations as most unscented transforms that guarantee third-order accuracy, which makes it applicable to a wide variety of applications, including the assimilation of observations in the modeling of the coronavirus (SARS-CoV-2) causing COVID-19.Treatment of osteoarthritis (OA) is mainly symptomatic by alleviating pain to postpone total joint replacement. Bone morphogenetic protein 7 (BMP7) is a candidate morphogen for experimental OA treatment that favorably alters the chondrocyte and cartilage phenotype. Intra-articular delivery and sustained release of a recombinant growth factor for treating OA are challenging, whereas the use of peptide technology potentially circumvents many of these challenges. In this study, we screened a high-resolution BMP7 peptide library and discovered several overlapping peptide sequences from two regions in BMP7 with nanomolar bioactivity that attenuated the pathological OA chondrocyte phenotype. A single exposure of OA chondrocytes to peptides p[63-82] and p[113-132] ameliorated the OA chondrocyte phenotype for up to 8 days, and peptides were bioactive on chondrocytes in OA synovial fluid. Peptides p[63-82] and p[113-132] required NKX3-2 for their bioactivity on chondrocytes and provoke changes in SMAD signaling activity. The bioactivity of p[63-82] depended on specific evolutionary conserved sequence elements common to BMP family members. Intra-articular injection of a rat medial meniscal tear (MMT) model with peptide p[63-82] attenuated cartilage degeneration. Together, this study identified two regions in BMP7 from which bioactive peptides are able to attenuate the OA chondrocyte phenotype. These BMP7-derived peptides provide potential novel disease-modifying treatment options for OA.There is growing attention and effort focused on treating the root cause of sensorineural hearing loss rather than managing associated secondary characteristic features. With recent substantial advances in understanding sensorineural hearing-loss mechanisms, gene delivery has emerged as a promising strategy for the biological treatment of hearing loss associated with genetic dysfunction. There are several successful and promising proof-of-principle examples of transgene deliveries in animal models; however, there remains substantial further progress to be made in these avenues before realizing their clinical application in humans. Herein, we review different aspects of development, ongoing preclinical studies, and challenges to the clinical transition of transgene delivery of the inner ear toward the restoration of lost auditory and vestibular function.Extracellular vesicles derived from mammalian cells could be useful carriers for drug delivery systems (DDSs); however, with regard to clinical application, there are several issues to be overcome. Acerola (Malpighia emarginata DC.) is a popular health food. In this study, the feasibility of orally administered nucleic acid drug delivery by acerola exosome-like nanoparticles (AELNs) was examined. AELNs were recovered from acerola juice using an affinity column instead of ultracentrifugation. MicroRNA (miRNA) was sufficiently encapsulated in AELNs by 30-min incubation on ice and was protected against RNase, strong acid, and base treatments. The administration of an AELN/miRNA mixture in cells achieved downregulation of the miRNA's target gene, and this mixture showed cytoplasmic localization. AELNs orally delivered small RNA to the digestive system in vivo. The target gene-suppressing effect in the small intestine and liver peaked 1 day after administration, indicating potential for use as an oral DDS for nucleic acid in the digestive system.We tested the hypothesis that voluntary wheel running would complement microdystrophin gene therapy to improve muscle function in young mdx mice, a model of Duchenne muscular dystrophy. mdx mice injected with a single dose of AAV9-CK8-microdystrophin or vehicle at age 7 weeks were assigned to three groups mdxRGT (run, gene therapy), mdxGT (no run, gene therapy), or mdx (no run, no gene therapy). Wild-type (WT) mice were assigned to WTR (run) and WT (no run) groups. WTR and mdxRGT performed voluntary wheel running for 21 weeks; remaining groups were cage active. Robust expression of microdystrophin occurred in heart and limb muscles of treated mice. mdxRGT versus mdxGT mice showed increased microdystrophin in quadriceps but decreased levels in diaphragm. mdx final treadmill fatigue time was depressed compared to all groups, improved in mdxGT, and highest in mdxRGT. Both weekly running distance (km) and final treadmill fatigue time for mdxRGT and WTR were similar. Remarkably, mdxRGT diaphragm power was only rescise in treated patients.

As a therapeutic enzyme, urate oxidase is utilized in the reduction of uric acid in various conditions such as gout or tumor syndrome lysis. However, even bearing kinetical advantage over other counterparts, it suffers from structural instability most likely due to its subcellular and fungal origin.

In this research, by using rational design and introduction of

disulfide bridge in urate oxidase structure, we designed and created a thermostable urate oxidase for the first time.

Utilizing site-directed mutagenesis and only with one point mutation we constructed two separate mutants Ala6Cys and Ser282Cys which covalently linked subunits of enzyme each other. Single mutation to cysteine created three inter-chain disulfide bridges and one hydrogen bond in Ala6Cys and two disulfide bridges in Ser282Cys.

Both mutants showed 10 °C increase in optimum activity compared to wild-type enzyme while the

values for both increased by 50% and their specific activity compromised. The thermal stability of Ser282Cys increased remarkably by comparing Ala6Cys and wild-type enzymes. Estimation of half life for wild-type enzyme demonstrated 38.5 min, while for Ala6Cys and Ser282Cys were 138 and 115 min, respectively. Interestingly, the optimal pH of both mutants was broaden from 7 to 10, which could make them candidates for industrial applications.

It seemed that introducing disulfide bridges resulted in local and overall rigidity by bringing two adjacent sites of enzyme together and decreasing the conformational entropy of unfolding state is responsible for the enhancement of thermostability.

It seemed that introducing disulfide bridges resulted in local and overall rigidity by bringing two adjacent sites of enzyme together and decreasing the conformational entropy of unfolding state is responsible for the enhancement of thermostability.

Dynamic light scattering (DLS) and electron microscopy (EM) are the most practical techniques for nanoparticles (NPs) characterization. However, the impediments which involved the sample preparation method lead to failure in provided results of mentioned device analysis. These problems will be intensifying, if the examined samples are the soft nanocarriers such as organic ones or biological samples.

In order to achieve the appropriate results from DLS and EM analysis, an optimized protocol was introduced by this research which would prepare samples with high degree of quality and accuracy.

Morphological analysis of prepared polymeric nanocarriers (micelles, nanogels) by this protocol were done. Filtration, dilution and sonication as three crucial and effectiveness steps of sample preparation were assessed through DLS data and EM images.

This research has tried to introduce a facile method with novelty of simplicity and rapidity. These triple steps could improve the quality of morphological data. The obtained results indicated that sample preparation methods have the most effective factors on sample size distribution and homogeneity of desired samples.

The suggested optimized preparation method will be helpful for all soft nanomaterial's samples.

The suggested optimized preparation method will be helpful for all soft nanomaterial's samples.

Glyphosate is a non-selective systemic herbicide with a broad spectrum of weed control that inhibits a key enzyme, 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase, in the shikimate pathway.

Isolation and analysis of the

(

) gene responsible for glyphosate-tolerance in bacteria from Roundup- contaminated soils was the aim of this study.

Sampling was done from the soil of the gardens which were heavily contaminated by Roundup herbicide and then bacterial screening was performed in the presence of high concentrations of glyphosate. The genus of bacterium was identified via molecular methods such as 16S rRNA sequencing. NVP-AEW541 manufacturer The

gene of this bacterium (



) was isolated using the primers designed-upon specific regions of

genes available in NCBI GenBank database. The PCR product was cloned, sequenced and subcloned into pET28a as an expression vector and transferred into E. coli strain BL21(DE3). The cells were inoculated in liquid M9 minimal medium containing IPTG and different concentrations of glyphosate.