Pathogenesis of sarcopenia and the relationship with fat mass: descriptive review.

Age-associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation leads to the redistribution of fat to the intra-abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing ß-oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro-inflammatory cytokines. In turn, these muscle-secreted cytokines may exacerbate adipose tissue atrophy, support chronic low-grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full-blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the 'obesity paradox', could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full-blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing.

Sterol metabolism and protein metabolism are differentially correlated with sarcopenia in Asian Chinese men and women.

OBJECTIVES: Our aim was to investigate the prevalence and predictive variables of sarcopenia. METHODS: We recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables. RESULTS: The prevalence of sarcopenia and sarcopenic obesity was 9.2%-16.2% and 0.26%-9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut-off value for age was 71 years, which departs from the commonly accepted cut-off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25-hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia. CONCLUSIONS: Our findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants.

Comparison of viral and epidemiological profiles of hospitalized children with severe acute respiratory infection in Beijing and Shanghai, China.

BACKGROUND: No comparison data have been reported on viral and epidemiological profiles of hospitalized children with severe acute respiratory infection (SARI) in Beijing or Shanghai, China. METHODS: We collected 700 nasopharyngeal aspirates (NPA) from hospitalized children with SARI in Beijing (northern China) and Shanghai (southern China). Multiple respiratory viruses (including 15 common viruses) were screened by validated polymerase chain reaction (PCR) or real-time reverse transcription-PCR assays and confirmed by sequencing. Demographic data and the distribution of viral infections were also examined. RESULTS: Of 700 samples, 547 (78.1%) tested positive for viral infections. The picornaviruses (PIC), which included rhinovirus (RV) and enterovirus (EV), were the most common (34.0%), followed by respiratory syncytial virus (RSV) (28.3%), human bocavirus (HBoV) (19.1%), adenovirus (ADV) (13.7%), human coronaviruses (HCoV) (10.7%), influenza A and B (8.9%), parainfluenza virus (PIV 1-3) (7.9%), and human metapneumovirus (HMPV) (5.0%). PIC (RV/EV) and RSV were the most prevalent etiological agents of SARI in both cities. The total and age-matched prevalence of RSV, HCoV, and hMPV among SARI children under 5 years old were significantly higher in Beijing than in Shanghai. Different age and seasonal distribution patterns of the viral infections were found between Beijing and Shanghai. CONCLUSIONS: Viral infection was tested and shown to be the most prevalent etiological agent among children with SARI in either the Beijing or the Shanghai area, while showing different patterns of viral and epidemiological profiles. Our findings provide a better understanding of the roles of geographic location and climate in respiratory viral infections in hospitalized children with SARI.

Detection of six common human paramyxoviruses in patients with acute febrile respiratory symptoms using a novel multiplex real-time RT-PCR assay.

Human metapneumovirus (hMPV), respiratory syncytial virus type A (RSV-A), RSV-B, and human parainfluenza viruses 1, 2, and 3 (HPIV-1, HPIV-2, and HPIV-3) are common respiratory paramyxoviruses. Here, we developed a two-tube triplex one-step real-time reverse-transcription polymerase chain reaction (real-time RT-PCR) and evaluated its performance using clinical samples. The data showed that this novel assay was 100% consistent with the monoplex real-time RT-PCR assay (in-house), which was superior to the commercial routine multiplex-ligation-NAT-based assay. Meanwhile, the clinical nasopharyngeal swabs of 471 patients with the acute febrile respiratory syndrome (AFRS) were analyzed using the established method. The results showed that 52 (11.7%) cases were positive for paramyxovirus. Among them, HPIVs and RSV-A had the highest detection rate. The age and seasonal distribution of human paramyxovirus infection were analyzed. In conclusion, we developed a novel multiplex real-time RT-PCR assay for the rapid detection of six common human paramyxoviruses, which were dominant in patients with AFRS in Qinghai.

Al2O3-Cu Substrate with Co-Continuous Phases Made by Powder Sintering Process.

Ceramic-Al substrates with co-continuous ceramic and metal phases, which exhibit high thermal conductivity and compatible coefficient of thermal expansion (CTE), have been widely investigated through the process of die-casting. In this research, a kind of powder sintering process was proposed for fabricating ceramic-Cu composite substrates with co-continuous phases. Copper fiber (Cuf) has excellent thermal conductivity and large aspect ratio, making it an ideal material to form bridging network structures in the ceramic-Cu composite. To maintain the large aspect ratio of Cuf, and densify the composite substrate, ZnO-SiO2-CaO glass was introduced as a sintering additive. Both Al2O3/glass/Cuf and Al2O3/30glass/Cup composite substrates were hot-pressed at 850 °C under 25 MPa. Experimental results showed that the thermal conductivity of Al2O3/30glass/30Cuf composite substrate was as high as 38.9 W/mK, which was about 6 times that of Al2O3/30glass; in contrast, the thermal conductivity of Al2O3/30glass/30Cup composite substrate was only 25.9 W/mK. Microstructure observation showed that, influenced by hot press and corrosion of molten ZnO-SiO2-CaO glass, the copper fibers were deformed under hot-pressing, and some local melting-like phenomena occurred on the surface of copper fiber at 850 °C under 25 MPa. The molten phase originating from surface of Cuf welded the overlapping node of copper fibers during cooling process. Finally, the interconnecting metal bridging in ceramic matrix was formed and behaved as a rapid heat-dissipating channel, which is similar to substrates prepared through die-casting process by porous ceramic and melted Al.

Genotypic Diversity and Epidemiology of Human Rhinovirus Among Children With Severe Acute Respiratory Tract Infection in Shanghai, 2013-2015.

Human rhinovirus (HRV), and particularly HRV-C, is increasingly recognized as a cause of severe acute respiratory infections (SARIs). However, little is known about the genotypic diversity and epidemiology of HRV among children with SARI. Thus, we investigated the genotypic diversity and epidemiology of HRV in children with SARI in China over a 2-year period. In total 1,003, nasopharyngeal aspirates were collected from children hospitalized with SARI in Shanghai from 2013 to 2015. HRV was screened for by a PCR method targeting the viral 5' UTR and was genotyped by sequencing of the VP4-VP2 region of the HRV genome. We also screened for 15 other common respiratory viruses to assess the prevalence of co-infection with HRV. The patient demographic and clinical data were reviewed. HRV was detected in 280 (27.9%) of the 1,003 specimens: HRV-A in 140 (14.0%), HRV-B in 21 (2.1%), HRV-C in 56 (5.6%), and HRV-untyped in 63 (6.3%). A phylogenetic analysis identified 77 genotypes (43 HRV-A, 10 HRV-B, and 24 HRV-C), among which A78, A12, A89, B70, C2, C6, and C24 predominated. HRV-A was detected mainly in winter 2013 and autumn 2014, while HRV-C detection peaked in autumn 2013 and 2014. The detection frequency of HRV-A was highest in patients <5 years old. Most HRV co-infections involved adenovirus, human bocavirus, and/or human respiratory syncytial virus. In conclusion, HRV-A and -C predominate in children with SARI in Shanghai. Among the 77 genotypes detected, A78, A12, A89, B70, C2, C6, and C24 were the most frequent. The HRV species responsible for SARIs differs according to season and age.

Safe and Sensitive Antiviral Screening Platform Based on Recombinant Human Coronavirus OC43 Expressing the Luciferase Reporter Gene.

Human coronaviruses (HCoVs) cause 15 to 30% of mild upper respiratory tract infections. However, no specific antiviral drugs are available to prevent or treat HCoV infections to date. Here, we developed four infectious recombinant HCoVs-OC43 (rHCoVs-OC43) which express the Renilla luciferase (Rluc) reporter gene. Among these four rHCoVs-OC43, rOC43-ns2DelRluc (generated by replacing ns2 with the Rluc gene) showed robust luciferase activity with only a slight impact on its growth characteristics. Additionally, this recombinant virus remained stable for at least 10 passages in BHK-21 cells. rOC43-ns2DelRluc was comparable to its parental wild-type virus (HCoV-OC43-WT) with respect to the quantity of the antiviral activity of chloroquine and ribavirin. We showed that chloroquine strongly inhibited HCoV-OC43 replication in vitro, with a 50% inhibitory concentration (IC50) of 0.33 µM. However, ribavirin showed inhibition of HCoV-OC43 replication only at high concentrations which may not be applicable to humans in clinical treatment, with an IC50 of 10 µM. Furthermore, using a luciferase-based small interfering RNA (siRNA) screening assay, we identified double-stranded-RNA-activated protein kinase (PKR) and DEAD box RNA helicases (DDX3X) that exhibited antiviral activities, which were further verified by the use of HCoV-OC43-WT. Therefore, rOC43-ns2DelRluc represents a promising safe and sensitive platform for high-throughput antiviral screening and quantitative analysis of viral replication.

[Molecular Detection and Genomic Characterization of Enterovirus D68 among Children with Severe Acute Respiratory Infection in Beijing and Shanghai].

To understand the prevalence and molecular typing of enterovirus D68 among children with severe acute respiratory infection(SARI)in Beijing and Shanghai,259 respiratory samples were collected from in Beijing during 2008-2010,and 441 respiratory samples were collected in Shanghai city between 2013and2014.All the samples were used for the screening of EV-D68 by nest RT-PCR and sequencing, and then EV-D68-positive samples were used for the complete genome sequencing through overlapping PCR. All available EV-D68full-length genomes collected from GenBank were used for phylogenetic analysis and comparison of EV-D68 types prevalent in China and America. One(0.4%)from 259 respiratory samples in Beijing was positive for EV-D68,and 4(0.9%)among the 441 samples from Shanghai were positive for EV-D68.Phylogenetic analysis of full length genome indicated that the EV-D68 prevalent in Beijing belong to Clade A2 and Clade B2,different from the American popular strains(Clade A1,Clade B1,Clade B4 and Clade B5).Partial sequence analysis declared phylogenetic conflict among different gene sequences. We concluded that the prevalence rate of EV-D68 among SARI Children in Beijing and Shanghai currently was lower(5/700;<1%),and the EV-D68 genotype prevalent in China and America belong to different clusters. Partial sequence analysis indicated that intratypic recombinant events may occur in EV-D68 prevalent in China.

[Development of Novel Multiplex Real-time RT-PCR Assays for Detection of MERS-CoV Infection].

We aimed to develop a novel laboratory assay for the detection of Middle East respiratory syndrome coronavirus (MERS-CoV) infection .Several novel multiplex real-time RT-PCR assays were developed using the upE,ORF1 band N2genes of MERS-CoV as targets; the novel assays were compared with previous monoplex real-time RT-PCR assays. For validation, we tested a MERS-CoV strain (hCoVEMC), clinical specimens from patients with fever in Shanghai, and specimens from the first imported MERS case in China. The detection limit of the novel multiplex real-time RT-PCR assays was 10 PFU of MERS-CoV per ml, the same as that in monoplex real-time RT-PCR assays based on upE or N2. The detection was specific for MERS-CoV. In validation using clinical samples, pharyngeal swabs from Shanghai patients were detected as negative, while swabs from the first imported MERS case in China were detected as positive. Using whole blood samples from a MERS case, better detection results were obtained with N2 as the target than upE. We conclude that all the novel assays established in this study could be used for the detection of MERS-CoV; they show potential for improvement compared with monoplex real-time RT-PCR assay based on upE.