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Abstract Background With the coming of the aging society, the incidence of elderly nasopharyngeal carcinoma (NPC) has been increasing which may result in considerable disease burden; however, the optimal treatment strategy for elderly patients is still debatable. Methods and Results Clinical data on 294 elderly NPC patients aged ≥70 treated between 2009 and 2019 was analyzed. Kaplan–Meier method was used to estimate overall survival (OS) and cancer‐specific survival (CSS) rates. With a median follow‐up of 53.25 months, the 5‐year estimated OS and CSS for the entire group were 59.5% and 69.8%, respectively. 146 patients died within the follow‐up period, of which recurrence + metastasis (48%) and internal medical disease unrelated to NPC (32%) are the primary causes of death. On univariable analysis, (IMRT vs. 3D‐CRT) (p = 0.001; p = 0.000), T stage (p = 0.001; p = 0.000), N stage (p = 0.013; p = 0.000) and clinical stage (p = 0.000; p = 0.000) were associated with OS and CSS; Charlson Comorbidity Index (CCI) (p = 0.016) was associated with OS. The addition of chemotherapy (CT) correlated with better CSS (p = 0.039), but did not improve OS (p = 0.056) for stage III–IV subgroup. On multivariate analysis, advanced clinical stage independently predicted poorer OS (p = 0.002) and CSS (p = 0.000). In addition, the application of IMRT was an independent protective factor on both OS (p = 0.028) and CSS (p = 0.030). Conclusion IMRT is a reasonable treatment strategy to improve survival for elderly NPC patients aged over 70 years; consideration of adding chemotherapy for elderly population should be weighed carefully.

Abstract Water adsorption‐driven heat transfer (AHT) technology has emerged as a promising solution to address crisis of the global energy consumption and environmental pollution of current heating and cooling processes. Hydrophilicity of water adsorbents plays a decisive role in these applications. This work reports an easy, green, and inexpensive approach to tuning the hydrophilicity of metal–organic frameworks (MOFs) by incorporating mixed linkers, isophthalic acid (IPA), and 3,5‐pyridinedicarboxylic acid (PYDC), with various ratios in a series of Al−xIPA‐(100−x)PYDC (x: feeding ratio of IPA) MOFs. The designed mixed‐linkers MOFs show a variation of hydrophilicity along the fraction of the linkers. Representative compounds with a proportional mixed linker ratio denoted as KMF‐2, exhibit an S‐shaped isotherm, an excellent coefficient of performance of 0.75 (cooling) and 1.66 (heating) achieved with low driving temperature below 70 °C which offers capability to employ solar or industrial waste heat, remarkable volumetric specific energy capacity (235 kWh m−3) and heat‐storage capacity (330 kWh m−3). The superiority of KMF‐2 to IPA or PYDC‐containing single‐linker MOFs (CAU‐10‐H and CAU‐10pydc, respectively) and most of benchmark adsorbents illustrate the effectiveness of the mixed‐linker strategy to design AHT adsorbents with promising performance.

Abstract Background Mitochondrial oxidative phosphorylation (OxPhos) is a critical regulator of skeletal muscle mass and function. Although muscle atrophy due to mitochondrial dysfunction is closely associated with bone loss, the biological characteristics of the relationship between muscle and bone remain obscure. We showed that muscle atrophy caused by skeletal muscle‐specific CR6‐interacting factor 1 knockout (MKO) modulates the bone marrow (BM) inflammatory response, leading to low bone mass. Methods MKO mice with lower muscle OxPhos were fed a normal chow or high‐fat diet and then evaluated for muscle mass and function, and bone mineral density. Immunophenotyping of BM immune cells was also performed. BM transcriptomic analysis was used to identify key factors regulating bone mass in MKO mice. To determine the effects of BM‐derived CXCL12 (C–X–C motif chemokine ligand 12) on regulation of bone homeostasis, a variety of BM niche‐resident cells were treated with recombinant CXCL12. Vastus lateralis muscle and BM immune cell samples from 14 patients with hip fracture were investigated to examine the association between muscle function and BM inflammation. Results MKO mice exhibited significant reductions in both muscle mass and expression of OxPhos subunits but increased transcription of mitochondrial stress response‐related genes in the extensor digitorum longus (P

Abstract Background Thyroid hormone excess induces protein energy wasting, which in turn promotes muscle weakness and bone loss in patients with Graves' disease. Although most studies have confirmed a relationship between thyrotoxicosis and muscle dysfunction, few have measured changes in plasma metabolites and immune cells during the development and recovery from thyrotoxic myopathy. The aim of this study was to identify specific plasma metabolites and T‐cell subsets that predict thyrotoxic myopathy recovery in patients with Graves' disease. Methods One hundred patients (mean age, 40.0 ± 14.2 years; 67.0% female), with newly diagnosed or relapsed Graves' disease were enrolled at the start of methimazole treatment. Handgrip strength and Five Times Sit to Stand Test performance time were measured at Weeks 0, 12, and 24. In an additional 35 patients (mean age, 38.9 ± 13.5 years; 65.7% female), plasma metabolites and immunophenotypes of peripheral blood were evaluated at Weeks 0 and 12, and the results of a short physical performance battery assessment were recorded at the same time. Results In both patient groups, methimazole‐induced euthyroidism was associated with improved handgrip strength and lower limb muscle function at 12 weeks. Elevated plasma metabolites including acylcarnitines were restored to normal levels at Week 12 regardless of gender, body mass index, or age (P trend

Abstract Background Programmed death‐ligand 1 (PD‐L1) has functional roles in cancer stem‐like cell (CSC) phenotypes and chemoresistance besides immune evasion. Chemotherapy is a common treatment choice for colorectal cancer (CRC) patients; however, chemoresistance limits its effectiveness of treatment. Methods We examined the role of S100A14 (SA14) in CRC by adopting PD‐L1high subpopulations within CRC cell lines and patient tumours, by establishing PD‐L1high chemoresistant CRC sublines through prolonged exposure to 5‐fluorouracil/oxaliplatin‐based chemotherapy in vitro and in vivo, and by analysing a public database. Results We identified a novel function of SA14 as a regulator of immune surveillance, major CSC phenotypes, and survival capacity under hostile microenvironments, including those harbouring chemotherapeutics, and as a prognostic biomarker in CRC. Mechanistically, SA14 inhibits PD‐L1 expression by directly interacting with signal transducer and activator of transcription 3 (STAT3) and inducing its proteasome‐mediated degradation. While gain‐of‐SA14 causes loss of PD‐L1 expression and tumourigenic potential and sensitisation to chemotherapy‐induced apoptosis in chemoresistant CRC cells, loss‐of‐SA14 causes increases in PD‐L1 expression, tumourigenic potential, and chemoresistance in vitro and in vivo. We further show that a combinatorial treatment with chemotherapy and recombinant SA14 protein effectively induces apoptosis in PD‐L1high chemoresistant CRC cells. Conclusions Our results suggest that SA14‐based therapy is an effective strategy to prevent tumour progression and that SA14 is a predictive biomarker for anti‐PD‐L1 immunotherapy and chemotherapy in combination.

Abstract Aims/Introduction Natural killer (NK) cells are cytotoxic lymphocytes critical to human immunity. Previous studies showed correlations between NK cell function and blood glucose concentrations. The purpose of the present study was to assess the NK cell activity and various metabolic parameters in people with type 2 diabetes, prediabetes and normal glucose tolerance. Materials and Methods A total of 49 participants were enrolled in the study. Anthropometric and biochemical parameters including age, sex, body mass index, smoking status, blood pressure, fasting plasma glucose, C‐peptide, insulin, glycated hemoglobin, total cholesterol, triglyceride, high‐density lipoprotein cholesterol and low‐density lipoprotein cholesterol were assessed. The 75 g oral glucose tolerance test was carried out for 2‐h postload glucose level. Homeostatic model assessment was calculated for insulin resistance and β‐cell function. NK cell activity was measured by detecting the circulating interferon‐gamma level secreted from NK cells. Results NK cell activity was lower in patients with type 2 diabetes (768.01 ± 650.35) compared with those with prediabetes (2,396.08 ± 653.76, P

Abstract Using direct conversion technology, normal adult somatic cells can be routinely switched from their original cell type into specific differentiated cell types by inducing the expression of differentiation‐related transcription factors. In this study, normal human dermal fibroblasts (NHDFs) are directly converted into cardiomyocyte‐like cells by drug and gene delivery using carboxymethylcellulose (CMC) nanoparticles (CiCMC‐NPs). CMC‐based multifunctional nanogels containing specific cardiomyocyte‐related genes are designed and fabricated, including GATA4, MEF2C, and TBX5 (GMT). However, GMT alone is insufficient, at least in vitro, in human fibroblasts. Hence, to inhibit proliferation and to induce differentiation, 5‐azacytidine (5‐AZA) is conjugated to the hydroxyl group of CMC in CiCMC‐NPs containing GMT; in addition, the CMC is coated with polyethylenimine. It is confirmed that the CiCMC‐NPs have nanogel properties, and that they exhibit the characteristic effects of 5‐AZA and GMT. When CiCMC‐NPs‐containing 5‐AZA and GMT are introduced into NHDFs, cardiomyocyte differentiation is initiated. In the reprogrammed cells, the mature cardiac‐specific markers cardiac troponin I and α‐actinin are expressed at twofold to threefold higher levels than in NHDFs. Engineered cells transplanted into live hearts exhibit active pumping ability within 1 day. Histology and immunohistology of heart tissue confirm the presence of transplanted engineered NHDF cells at injection sites.

Background. The prevalence of coronary artery stenosis (CAS) at the initiation of renal replacement therapy (RRT) in chronic kidney disease (CKD) patients has not been fully elucidated. Although coronary angiography is the gold standard in diagnosing CAS its invasiveness and economic burden lead to searching for a noninvasive alternative method. In this study, we evaluated the prevalence of CAS by multidetector row computed tomography (MDCT) and related risk factor to articulate the usefulness of MDCT. Method. Seventy-four asymptomatic CKD patients who began dialysis were evaluated with echocardiography and MDCT. The patients were stratified into two groups according to CAS and coronary artery calcification score (CACS) by MDCT to detect silent CAS and evaluate its predictability for cardiac events. Results. CAS was seen in 24 (32.4%) of 74 asymptomatic CKD patients on MDCT. Both groups showed increasing frequencies of CAS with age (P