Background
Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ...ageing‐related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons.
Methods
A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non‐sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty‐two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre‐intensive and post‐intensive lifestyle interventions, were measured.
Results
The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non‐sarcopenic subjects, serum interleukin (IL)‐6, IL‐18, tumour necrosis factor‐α (TNF‐α), TNF‐like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF‐α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6‐fold and 14.3‐fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4‐fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF‐α, IL‐18, insulin, and adiponectin (all P < 0.05).
Conclusions
High levels of the inflammatory cytokines TWEAK and TNF‐α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could significantly improve muscle mass, reduce inflammation, and restore metabolic hormone levels in sarcopenic patients. This trial was registered at clinicaltrials.gov as NCT02873676.
Severe cognitive decline is a hallmark of Alzheimer’s disease (AD). In addition to gray matter loss, significant white matter pathology has been identified in AD patients. Here, we characterized the ...dynamics of myelin generation and loss in the APP/PS1 mouse model of AD. Unexpectedly, we observed a dramatic increase in the rate of new myelin formation in APP/PS1 mice, reminiscent of the robust oligodendroglial response to demyelination. Despite this increase, overall levels of myelination are decreased in the cortex and hippocampus of APP/PS1 mice and postmortem AD tissue. Genetically or pharmacologically enhancing myelin renewal, by oligodendroglial deletion of the muscarinic M1 receptor or systemic administration of the pro-myelinating drug clemastine, improved the performance of APP/PS1 mice in memory-related tasks and increased hippocampal sharp wave ripples. Taken together, these results demonstrate the potential of enhancing myelination as a therapeutic strategy to alleviate AD-related cognitive impairment.
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•New myelin formation is increased in adult APP/PS1 mice•Extensive myelin loss occurs in APP/PS1 mice and individuals with AD•Pro-myelinating strategies enhance myelin renewal and alleviate myelin loss in APP/PS1 mice•Enhanced myelin renewal rescues deficits in cognition and hippocampal physiology in APP/PS1 mice
Chen et al. demonstrate that myelin formation is increased in APP/PS1 mice, reminiscent of a regenerative response to extensive demyelination, and that pro-myelinating strategies enhance myelin renewal, rescue cognitive deficits, and increase hippocampal sharp wave ripples in APP/PS1 mice.
Polychlorinated dibenzo-p-dioxins (PCDDs), as a class of persistent and highly toxic organic pollutants, have been posing a great threat to human health and the environment. The sensing of these ...compounds is important but challenging. Here, we report a highly stable zirconium-based metal-organic framework (MOF), Zr
O
(OH)
(HCOO)
(CPTTA)
(BUT-17) with one-dimensional hexagonal channels and phenyl-rich pore surfaces for the recognition and sensing of two representative PCDDs, 2,3-dichlorodibenzo-p-dioxin (BCDD) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), based on the fluorescence quenching. BUT-17 exhibits high sensing ability with the detection limits as low as 27 and 57 part per billion toward BCDD and TCDD, respectively, and is very selective as well without the interference of similar compounds. The recognition of BUT-17 toward BCDD is demonstrated by single-crystal structure of its guest-loaded phase, in which the fluorescence-quenched complexes form between the adsorbed BCDD molecules and the MOF host through π-π stacking and hydrogen bonding interactions.
Metal–organic frameworks (MOFs) have emerged as porous solids of a superior type for the fabrication of membranes. However, it is still challenging to prepare a uniformly dispersed robust MOF hybrid ...membrane. Herein, we propose a simple and powerful strategy, namely, coordination‐driven in situ self‐assembly, for the fabrication of MOF hybrid membranes. On the basis of the coordination interactions between metal ions and ligands and/or the functional groups of the organic polymer, this method was confirmed to be feasible for the production of a stable membrane with greatly improved MOF‐particle dispersion in and compatibility with the polymer, thus providing outstanding separation ability. As an experimental proof of concept, a high‐quality ZIF‐8/PSS membrane was fabricated that showed excellent performance in the nanofiltration and separation of dyes from water.
Mopping up the mess: A hybrid membrane composed of the metal–organic framework (MOF) ZIF‐8 and poly(sodium 4‐styrenesulfonate) was prepared by a coordination‐driven in situ self‐assembly method. The MOF particles were well‐dispersed in the polymer in the resulting stable membrane (see picture), which showed excellent performance in the nanofiltration and separation of dyes from water.
As a widely recognized standard regimen, R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is able to cure two-thirds patients with diffuse large B cell lymphoma ...(DLBCL), and the remaining patients suffer from refractory or relapsed disease due to resistance to R-CHOP and fare poorly. Unsatisfied outcomes for those relapsed/refractory patients prompted efforts to discover new treatment approaches for DLBCL, including chimeric antigen receptor T cells, bispecific T cell engagers, immunomodulatory drugs, immune checkpoint inhibitors, monoclonal antibodies, antibody-drug conjugates, molecular pathway inhibitors, and epigenetic-modifying drugs. Herein, up-to-date data about the most promising treatment approaches for DLBCL are recapitulated, and novel genetic classification systems are introduced to guide individualized treatment for DLBCL.
The exotic topological surface states of Dirac or Weyl semimetals, namely Fermi arcs, are predicted to be spin polarized, while their spin polarization nature is still not revealed by transport ...measurements. Here, we report the spin-polarized transport in a Dirac semimetal Cd_{3}As_{2} nanowire employing the ferromagnetic electrodes for spin detection. The spin-up and spin-down states can be changed by reversing the current polarity, showing the spin-momentum locking property. Moreover, the nonlocal measurements show a high fidelity of the spin signals, indicating the topological protection nature of the spin transport. As tuning the Fermi level away from the Dirac point by gate voltages, the spin signals gradually decrease and finally are turned off, which is consistent with the fact that the Fermi arc surface state has the maximum ratio near the Dirac point and disappears above the Lifshitz transition point. Our results should be valuable for revealing the transport properties of the spin-polarized Fermi arc surface states in topological semimetals.
•Low or high doses of VLP HPV vaccine were well tolerated in 9–45 year-old females.•Three HPV vaccinations elicited protective immune responses in 100% of vaccinees.•HPV vaccination did not result in ...any severe or serious adverse event.•Reactogenicity and immunogenicity were not affected by increasing dosage of HPV vaccine.
We evaluated the safety and immunogenicity of high and low doses of a novel pichia pastoris-expressed bivalent (types 16 and 18) human papillomavirus (HPV) virus-like particle vaccine.
In this randomized, double-blind, placebo-controlled phase 1 trial, we enrolled 160 healthy females aged 9–45 years in Guangxi, China who were randomized (1:1:2) to receive either low (0.5 mL) or high (1.0 mL) dosages of bivalent HPV vaccine, or placebo (aluminum adjuvant) in a 0, 2, 6 months schedule. Adverse events and other significant conditions that occurred within 30 days after each vaccination were recorded throughout the trial. Sera were collected at days 0, 60, 180 and 210 to measure anti-HPV 16/18 neutralizing antibodies.
A total of 160 participants received at least one dose of the HPV vaccine and 152 completed the three dose vaccination series. Reporting rates of adverse events in placebo, low dose (0.5 mL) and high dose (1.0 mL) groups were 47.5 %, 55.0 % and 55.0 %, respectively. No serious adverse events occurred during this trial. 100 % of the participants who received three doses of the HPV vaccine produced neutralizing antibodies against HPV 16/18 vaccine. For HPV 16 and HPV 18, the geometric mean titers (GMTs) were similar between the low dose group (GMTHPV 16 = 10816 95 % CI: 7824–14953), GMTHPV 18 = 3966 95 % CI: 2693–5841) and high dose group (GMT HPV 16 = 14482 95 % CI: 10848–19333, GMT HPV 18 = 3428 95 % CI: 2533–4639).
The pichia pastoris-expressed bivalent HPV vaccine was safe and immunogenic in Chinese females aged 9–45 years. The low dosage (0.5 mL) was selected for further immunogenicity and efficacy study.
Antibiotics and organic explosives are among the main organic pollutants in wastewater; their detection and removal are quite important but challenging. As a new class of porous materials, ...metal–organic frameworks (MOFs) are considered as a promising platform for the sensing and adsorption applications. In this work, guided by a topological design approach, two stable isostructural Zr(IV)-based MOFs, Zr6O4(OH)8(H2O)4(CTTA)8/3 (BUT-12, H3CTTA = 5′-(4-carboxyphenyl)-2′,4′,6′-trimethyl-1,1′:3′,1″-terphenyl-4,4″-dicarboxylic acid) and Zr6O4(OH)8(H2O)4(TTNA)8/3 (BUT-13, H3TTNA = 6,6′,6″-(2,4,6-trimethylbenzene-1,3,5-triyl)tris(2-naphthoic acid)) with the the-a topological structure constructed by D 4h 8-connected Zr6 clusters and D 3h 3-connected linkers were designed and synthesized. The two MOFs are highly porous with the Brunauer–Emmett–Teller surface area of 3387 and 3948 m2 g–1, respectively. Particularly, BUT-13 features one of the most porous water-stable MOFs reported so far. Interestingly, these MOFs represent excellent fluorescent properties, which can be efficiently quenched by trace amounts of nitrofurazone (NZF) and nitrofurantoin (NFT) antibiotics as well as 2,4,6-trinitrophenol (TNP) and 4-nitrophenol (4-NP) organic explosives in water solution. They are responsive to NZF and TNP at parts per billion (ppb) levels, which are among the best performing luminescent MOF-based sensing materials. Simultaneously, both MOFs also display high adsorption abilities toward these organic molecules. It was demonstrated that the adsorption plays an important role in the preconcentration of analytes, which can further increase the fluorescent quenching efficiency. These results indicate that BUT-12 and -13 are favorable materials for the simultaneous selective detection and removal of specific antibiotics and organic explosives from water, being potentially useful in monitoring water quality and treating wastewater.
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