Hereditary kidney diseases are common causes of chronic kidney disease (CKD) in children and adolescents, and also has an important role in the onset and progression of CKD in adulthood. Constructing ...a data sharing registration system for hereditary kidney disease and forming representative data with Chinese population specificity, is of great significance for achieving phenotype and genotype characterization, improving precision management level and mechanism research. The high heterogeneity of the disease and the scattered distribution of patients have led to a lack of understanding and unified management standards for hereditary kidney disease. Led by pediatric nephrology specialists and geneticists, integrating data sources from various centers can leverage clinical resource advantages. Focusing on different subtype disease cohorts, integrating and analyzing data such as genotype, multi-omics, and clinical outcomes, can achieve breakthroughs in the key points of disease diagnosis and treatment.
Background
Sarcopenia is an age-related disease, which is characterized by a decline in muscle mass and function. It is one of the most important health issues in the elderly and often leads to a ...high rate and variety of adverse outcomes.
Objectives
To evaluate the screening accuracy of SARC-F for sarcopenia in the elderly.
Design
We conducted a meta-analysis using articles available in 6 databases including PubMed (Medline), Web of Science, Embase, Cochrane Controlled Register of Trials (CENTRAL), China Knowledge Resource Integrated Database (CNKI), and Wanfang databases from inception to May 2020. Participants: Adults aged 60 years and older.
Measurements
Sarcopenia was defined by EWGSOP2, EWGSOP, AWGS, FNIH and IWGS. Two authors independently extracted data based on predefined criteria. Where data were available we calculated pooled summary estimates of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and their 95% confidence interval (CI) based on different criteria using the hierarchical logistic regression modeling including bivariate modeling and hierarchical summary receiver operating characteristic (HSROC) modeling.
Results
We included 20 studies, with the prevalence of sarcopenia ranging from 6.42% to 21.56%. The number of the literatures using EWGSOP, EWGSOP2, AWGS, IWGS and FNIH as diagnostic criteria was 13, 4, 13, 8, 7, respectively. Bivariate analysis yielded a pooled sensitivity of 32% (95%CI: 19%–47%), 77% (95%CI: 49%–92%), 27% (95%CI: 16%–42%), 39% (95%CI: 27%–52%), 35% (95%CI: 23%–49%) and a pooled specificity of 86% (95%CI:77%–92%), 63% (95%CI: 43%–79%), 91% (95%CI: 85%–95%), 86% (95%CI: 76%–92%), 89% (95%CI: 81%–93%), respectively. The area under the HSROC curve were 0.68 (95%CI: 0.64–0.72), 0.75 (95%CI: 0.71–0.78), 0.73 (95%CI: 0.69–0.77), 0.67 (95%CI: 0.62–0.71), 0.70 (95%CI: 0.65–0.73), respectively.
Conclusions
The screening accuracy of SARC-F was various based on different diagnostic criteria. There were some limitations for SARC-F, however, considering the higher practicability and specificity for screening sarcopenia in practice, SARC-F was still an effective screening tool for sarcopenia in the elderly. And the screening accuracy of SARC-F needs further exploration when EWGSOP2 is applied as diagnostic criteria and geriatric inpatients are the target participants.
An intensive investigation of carbonaceous PM2.5 and TSP (total suspended particles) from Pudong (China) was conducted as part of the MIRAGE-Shanghai (Megacities Impact on Regional and Global ...Environment) experiment in 2009. Data for organic and elemental carbon (OC and EC), organic species, including C17 to C40 n-alkanes and 17 polycyclic aromatic hydrocarbons (PAHs), and stable carbon isotopes OC (δ13COC) and EC (δ13CEC) were used to evaluate the aerosols' temporal variations and identify presumptive sources. High OC/EC ratios indicated a large fraction of secondary organic aerosol (SOA); high char/soot ratios indicated stronger contributions to EC from motor vehicles and coal combustion than biomass burning. Diagnostic ratios of PAHs indicated that much of the SOA was produced via coal combustion. Isotope abundances (δ13COC = −24.5 ± 0.8‰ and δ13CEC = −25.1 ± 0.6‰) indicated that fossil fuels were the most important source for carbonaceous PM2.5 (particulate matter less than 2.5 micrometers in diameter), with lesser impacts from biomass burning and natural sources. An EC tracer system and isotope mass balance calculations showed that the relative contributions to total carbon from coal combustion, motor vehicle exhaust, and SOA were 41%, 21%, and 31%; other primary sources such as marine, soil and biogenic emissions contributed 7%. Combined analyses of OC and EC, n-alkanes and PAHs, and stable carbon isotopes provide a new way to apportion the sources of carbonaceous particles.
The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global crisis. Replication of SARS-CoV-2 requires the viral ...RNA-dependent RNA polymerase (RdRp) enzyme, a target of the antiviral drug remdesivir. Here we report the cryo-electron microscopy structure of the SARS-CoV-2 RdRp, both in the apo form at 2.8-angstrom resolution and in complex with a 50-base template-primer RNA and remdesivir at 2.5-angstrom resolution. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp, where remdesivir is covalently incorporated into the primer strand at the first replicated base pair, and terminates chain elongation. Our structures provide insights into the mechanism of viral RNA replication and a rational template for drug design to combat the viral infection.
Autophagy is essential for cellular survival and energy homeostasis under nutrient deprivation. Despite the emerging importance of nuclear events in autophagy regulation, epigenetic control of ...autophagy gene transcription remains unclear. Here, we report fasting-induced Fibroblast Growth Factor-21 (FGF21) signaling activates hepatic autophagy and lipid degradation via Jumonji-D3 (JMJD3/KDM6B) histone demethylase. Upon FGF21 signaling, JMJD3 epigenetically upregulates global autophagy-network genes, including Tfeb, Atg7, Atgl, and Fgf21, through demethylation of histone H3K27-me3, resulting in autophagy-mediated lipid degradation. Mechanistically, phosphorylation of JMJD3 at Thr-1044 by FGF21 signal-activated PKA increases its nuclear localization and interaction with the nuclear receptor PPARα to transcriptionally activate autophagy. Administration of FGF21 in obese mice improves defective autophagy and hepatosteatosis in a JMJD3-dependent manner. Remarkably, in non-alcoholic fatty liver disease patients, hepatic expression of JMJD3, ATG7, LC3, and ULK1 is substantially decreased. These findings demonstrate that FGF21-JMJD3 signaling epigenetically links nutrient deprivation with hepatic autophagy and lipid degradation in mammals.
Photovoltaics based on nanowire arrays could reduce cost and materials consumption compared with planar devices but have exhibited low efficiency of light absorption and carrier collection. We ...fabricated a variety of millimeter-sized arrays of p-type/intrinsic/n-type (p-i-n) doped InP nanowires and found that the nanowire diameter and the length of the top n-segment were critical for cell performance. Efficiencies up to 13.8% (comparable to the record planar InP cell) were achieved by using resonant light trapping in 180-nanometer-diameter nanowires that only covered 12% of the surface. The share of sunlight converted into photocurrent (71%) was six times the limit in a simple ray optics description. Furthermore, the highest open-circuit voltage of 0.906 volt exceeds that of its planar counterpart, despite about 30 times higher surface-to-volume ratio of the nanowire cell.
Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin ...of cosmological FRBs is still not settled. Here we report the detection of1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref.9). These observations show irregular short-time variation ofthe Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (au; Earth-Sun distance) ofthe source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.
Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a heterotrimeric αβγ complex that functions as a central regulator of energy homeostasis. Energy stress manifests as a drop in the ...ratio of adenosine triphosphate (ATP) to AMP/ADP, which activates AMPK's kinase activity, allowing it to upregulate ATP-generating catabolic pathways and to reduce energy-consuming catabolic pathways and cellular programs. AMPK senses the cellular energy state by competitive binding of the three adenine nucleotides AMP, ADP, and ATP to three sites in its γ subunit, each, which in turn modulates the activity of AMPK's kinase domain in its α subunit. Our current understanding of adenine nucleotide binding and the mechanisms by which differential adenine nucleotide occupancies activate or inhibit AMPK activity has been largely informed by crystal structures of AMPK in different activity states. Here we provide an overview of AMPK structures, and how these structures, in combination with biochemical, biophysical, and mutational analyses provide insights into the mechanisms of adenine nucleotide binding and AMPK activity modulation.
Most cancer cells exhibit increased glycolysis and use this metabolic pathway for generation of ATP as a main source of their energy supply. This phenomenon is known as the Warburg effect and is ...considered as one of the most fundamental metabolic alterations during malignant transformation. In recent years, there are significant progresses in our understanding of the underlying mechanisms and the potential therapeutic implications. Biochemical and molecular studies suggest several possible mechanisms by which this metabolic alteration may evolve during cancer development. These mechanisms include mitochondrial defects and malfunction, adaptation to hypoxic tumor microenvironment, oncogenic signaling, and abnormal expression of metabolic enzymes. Importantly, the increased dependence of cancer cells on glycolytic pathway for ATP generation provides a biochemical basis for the design of therapeutic strategies to preferentially kill cancer cells by pharmacological inhibition of glycolysis. Several small molecules have emerged that exhibit promising anticancer activity in vitro and in vivo, as single agent or in combination with other therapeutic modalities. The glycolytic inhibitors are particularly effective against cancer cells with mitochondrial defects or under hypoxic conditions, which are frequently associated with cellular resistance to conventional anticancer drugs and radiation therapy. Because increased aerobic glycolysis is commonly seen in a wide spectrum of human cancers and hypoxia is present in most tumor microenvironment, development of novel glycolytic inhibitors as a new class of anticancer agents is likely to have broad therapeutic applications.
Semiconductor InSb nanowires are expected to provide an excellent material platform for the study of Majorana fermions in solid state systems. Here, we report on the realization of a Nb–InSb ...nanowire–Nb hybrid quantum device and the observation of a zero-bias conductance peak structure in the device. An InSb nanowire quantum dot is formed in the device between the two Nb contacts. Due to the proximity effect, the InSb nanowire segments covered by the superconductor Nb contacts turn to superconductors with a superconducting energy gap Δ InSb ∼ 0.25 meV. A tunable critical supercurrent is observed in the device in high back gate voltage regions in which the Fermi level in the InSb nanowire is located above the tunneling barriers of the quantum dot and the device is open to conduction. When a perpendicular magnetic field is applied to the devices, the critical supercurrent is seen to decrease as the magnetic field increases. However, at sufficiently low back gate voltages, the device shows the quasi-particle Coulomb blockade characteristics and the supercurrent is strongly suppressed even at zero magnetic field. This transport characteristic changes when a perpendicular magnetic field stronger than a critical value, at which the Zeeman energy in the InSb nanowire is E z ∼ Δ InSb , is applied to the device. In this case, the transport measurements show a conductance peak at the zero bias voltage and the entire InSb nanowire in the device behaves as in a topological superconductor phase. We also show that this zero-bias conductance peak structure can persist over a large range of applied magnetic fields and could be interpreted as a transport signature of Majorana fermions in the InSb nanowire.
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