Abstract
MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18–25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the ...biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA–target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA–target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.
Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health
. Despite intense research efforts, how, when and where ...new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing
of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China
. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.
Background
Diagnostic criteria for sarcopenia have not been established in Chinese. This study established criteria based on the L3‐skeletal muscle index (L3‐SMI) and assessed its value for outcomes ...predicting in cirrhotic Chinese patients.
Methods
Totally 911 subjects who underwent a CT scan at two centres were enrolled in Cohort 1 (394 male and 417 female subjects, aged 20–80 years). The data of those subjects younger than 60 years (365 male and 296 female subjects) were used to determine the reference intervals of the L3‐SMI and its influencing factors. Cohort 2 consisted of 480 patients (286 male and 184 female patients) from three centres, and their data were used to investigate the prevalence of sarcopenia and evaluate the value of L3‐SMI for predicting the prognosis and complications of cirrhosis.
Results
Age and sex had the greatest effects on the L3‐SMI (P < 0.001). The L3‐SMI scores were clearly higher in male patients than in female patients (52.94 ± 8.41 vs. 38.91 ± 5.65 cm2/m2, P < 0.001) and sharply declined in subjects aged ≥ 60 years. Based on the mean −1.28 × SD among adults aged < 60 years, the L3‐SMI cut‐off value for sarcopenia was 44.77 cm2/m2 in male patients and 32.50 cm2/m2 in female patients. Using these values, 22.5% of the cirrhotic patients (28.7% of male patients and 11.9% of female patients) were diagnosed with sarcopenia. Compared with non‐sarcopenia individuals, sarcopenia patients had lower body mass index (21.28 ± 3.01 vs. 24.09 ± 3.39 kg/m2, P < 0.001) and serum albumin levels (31.54 ± 5.93 vs. 32.93 ± 5.95 g/L, P = 0.032), longer prothrombin times (16.39 ± 3.05 vs. 15.71 ± 3.20 s, P = 0.049), higher total bilirubin concentrations (41.33 ± 57.38 vs. 32.52 ± 31.48 μmol/L, P = 0.039), worse liver function (Child–Pugh score, 8.05 ± 2.11 vs. 7.32 ± 2.05, P = 0.001), higher prevalence of cirrhosis‐related complications (81.82% vs. 62.24%, P < 0.001) and mortality (30.68% vs. 11.22%, P < 0.001). Overall survival was significantly lower in the sarcopenia group risk ratio (RR) = 2.643, 95% confidence interval (CI) 1.646–4.244, P < 0.001, accompanied with an increased cumulative incidence of ascites (RR = 1.827, 95% CI 1.259–2.651, P = 0.002), spontaneous bacterial peritonitis (RR = 3.331, 95% CI 1.404–7.903, P = 0.006), hepatic encephalopathy (RR = 1.962, 95% CI 1.070–3.600, P = 0.029), and upper gastrointestinal varices (RR = 2.138, 95% CI 1.319–3.466, P = 0.002). Subgroup analysis showed sarcopenia shortened the survival of the patients with Model For End‐Stage Liver Disease score > 14 (RR = 4.310, 95% CI 2.091–8.882, P < 0.001) or Child–Pugh C (RR = 3.081, 95% CI 1.516–6.260, P = 0.002).
Conclusions
Sarcopenia is a common comorbidity of cirrhosis and can be used to predict cirrhosis‐related complications and the prognosis.
The extremely high brightness temperatures of pulsars and fast radio bursts (FRBs) require their radiation mechanisms to be coherent. Coherent curvature radiation from bunches has been long discussed ...as the mechanism for radio pulsars and recently for FRBs. Assuming that bunches are already generated in pulsar magnetospheres, we calculate the spectrum of coherent curvature radiation under a three-dimensional magnetic field geometry. Different from previous works assuming parallel trajectories and a monoenergetic energy distribution of electrons, we consider a bunch characterized by its length, curvature radius of the trajectory family, bunch opening angle, and electron energy distribution. We find that the curvature radiation spectra of the bunches are characterized by a multisegment broken power law, with the break frequencies depending on bunch properties and trajectory configuration. We also emphasize that in a pulsar magnetosphere, only the fluctuation of net charges with respect to the background (Goldreich-Julian) outflow can make a contribution to coherent radiation. We apply this model to constrain the observed spectra of pulsars and FRBs. For a typical pulsar ( , P = 0.1 s), a small fluctuation of the net charge δnGJ ∼ 0.1nGJ can provide the observable flux. For FRBs, the fluctuating net charge may be larger due to its abrupt nature. For δnGJ ∼ nGJ, a neutron star with a strong magnetic field and fast rotation is required to power an FRB in the spindown-powered model. The requirement is less stringent in the cosmic comb model thanks to the larger cross section and compressed charge density of the bunch made by the external astrophysical stream that combs the magnetosphere.
The 2019 novel coronavirus (2019-nCoV) causing an outbreak of pneumonia in Wuhan, Hubei province of China was isolated in January 2020. This study aims to investigate its epidemiologic history, and ...analyze the clinical characteristics, treatment regimens, and prognosis of patients infected with 2019-nCoV during this outbreak.
Clinical data from 137 2019-nCoV-infected patients admitted to the respiratory departments of nine tertiary hospitals in Hubei province from December 30, 2019 to January 24, 2020 were retrospectively collected, including general status, clinical manifestations, laboratory test results, imaging characteristics, and treatment regimens.
None of the 137 patients (61 males, 76 females, aged 20-83 years, median age 57 years) had a definite history of exposure to Huanan Seafood Wholesale Market. Major initial symptoms included fever (112/137, 81.8%), coughing (66/137, 48.2%), and muscle pain or fatigue (44/137, 32.1%), with other, less typical initial symptoms observed at low frequency, including heart palpitations, diarrhea, and headache. Nearly 80% of the patients had normal or decreased white blood cell counts, and 72.3% (99/137) had lymphocytopenia. Lung involvement was present in all cases, with most chest computed tomography scans showing lesions in multiple lung lobes, some of which were dense; ground-glass opacity co-existed with consolidation shadows or cord-like shadows. Given the lack of effective drugs, treatment focused on symptomatic and respiratory support. Immunoglobulin G was delivered to some critically ill patients according to their conditions. Systemic corticosteroid treatment did not show significant benefits. Notably, early respiratory support facilitated disease recovery and improved prognosis. The risk of death was primarily associated with age, underlying chronic diseases, and median interval from the appearance of initial symptoms to dyspnea.
The majority of patients with 2019-nCoV pneumonia present with fever as the first symptom, and most of them still showed typical manifestations of viral pneumonia on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis.
The 2019 novel coronavirus has caused the outbreak of the acute respiratory disease in Wuhan, Hubei Province of China since December 2019. This study was performed to analyze the clinical ...characteristics of patients who succumbed to and who recovered from 2019 novel coronavirus disease (COVID-19).
Clinical data were collected from two tertiary hospitals in Wuhan. A retrospective investigation was conducted to analyze the clinical characteristics of fatal cases of COVID-19 (death group) and we compare them with recovered patients (recovered group). Continuous variables were analyzed using the Mann-Whitney U test. Categorical variables were analyzed by χ test or Fisher exact test as appropriate.
Our study enrolled 109 COVID-19 patients who died during hospitalization and 116 recovered patients. The median age of the death group was older than the recovered group (69 62, 74 vs. 40 33, 57 years, Z = 9.738, P < 0.001). More patients in the death group had underlying diseases (72.5% vs. 41.4%, χ = 22.105, P < 0.001). Patients in the death group had a significantly longer time of illness onset to hospitalization (10.0 6.5, 12.0 vs. 7.0 5.0, 10.0 days, Z = 3.216, P = 0.001). On admission, the proportions of patients with symptoms of dyspnea (70.6% vs. 19.0%, χ = 60.905, P < 0.001) and expectoration (32.1% vs. 12.1%, χ = 13.250, P < 0.001) were significantly higher in the death group. The blood oxygen saturation was significantly lower in the death group (85 77, 91% vs. 97 95, 98%, Z = 10.625, P < 0.001). The white blood cell (WBC) in death group was significantly higher on admission (7.23 4.87, 11.17 vs. 4.52 3.62, 5.88 ×10/L, Z = 7.618, P < 0.001). Patients in the death group exhibited significantly lower lymphocyte count (0.63 0.40, 0.79 vs. 1.00 0.72, 1.27 ×10/L, Z = 8.037, P < 0.001) and lymphocyte percentage (7.10 4.45, 12.73% vs. 23.50 15.27, 31.25%, Z = 10.315, P < 0.001) on admission, and the lymphocyte percentage continued to decrease during hospitalization (7.10 4.45, 12.73% vs. 2.91 1.79, 6.13%, Z = 5.242, P < 0.001). Alanine transaminase (22.00 15.00, 34.00 vs. 18.70 13.00, 30.38 U/L, Z = 2.592, P = 0.010), aspartate transaminase (34.00 27.00, 47.00 vs. 22.00 17.65, 31.75 U/L, Z = 7.308, P < 0.001), and creatinine levels (89.00 72.00, 133.50 vs. 65.00 54.60, 78.75 μmol/L, Z = 6.478, P < 0.001) were significantly higher in the death group than those in the recovered group. C-reactive protein (CRP) levels were also significantly higher in the death group on admission (109.25 35.00, 170.28 vs. 3.22 1.04, 21.80 mg/L, Z = 10.206, P < 0.001) and showed no significant improvement after treatment (109.25 35.00, 170.28 vs. 81.60 27.23, 179.08 mg/L, Z = 1.219, P = 0.233). The patients in the death group had more complications such as acute respiratory distress syndrome (ARDS) (89.9% vs. 8.6%, χ = 148.105, P < 0.001), acute cardiac injury (59.6% vs. 0.9%, χ = 93.222, P < 0.001), acute kidney injury (18.3% vs. 0%, χ = 23.257, P < 0.001), shock (11.9% vs. 0%, χ = 14.618, P < 0.001), and disseminated intravascular coagulation (DIC) (6.4% vs. 0%, χ = 7.655, P = 0.006).
Compared to the recovered group, more patients in the death group exhibited characteristics of advanced age, pre-existing comorbidities, dyspnea, oxygen saturation decrease, increased WBC count, decreased lymphocytes, and elevated CRP levels. More patients in the death group had complications such as ARDS, acute cardiac injury, acute kidney injury, shock, and DIC.
Cadmium (Cd) is a high‐risk pathogenic toxin for hepatic diseases. Excessive mitophagy is a hallmark in Cd‐induced hepatotoxicity. However, the underlying mechanism remains obscure. Mitochondrial ...calcium uniporter (MCU) is a key regulator for mitochondrial and cellular homeostasis. Here, Cd exposure upregulated MCU expression and increased mitochondrial Ca2+ uptake are found. MCU inhibition through siRNA or by Ru360 significantly attenuates Cd‐induced excessive mitophagy, thereby rescues mitochondrial dysfunction and increases hepatocyte viability. Heterozygous MCU knockout mice exhibit improved liver function, ameliorated pathological damage, less mitochondrial fragmentation, and mitophagy after Cd exposure. Mechanistically, Cd upregulates MCU expression through phosphorylation activation of cAMP‐response element binding protein at Ser133(CREBS133) and subsequent binding of MCU promoter at the TGAGGTCT, ACGTCA, and CTCCGTGATGTA regions, leading to increased MCU gene transcription. The upregulated MCU intensively interacts with voltage‐dependent anion‐selective channel protein 1 (VDAC1), enhances its dimerization and ubiquitination, resulting in excessive mitophagy. This study reveals a novel mechanism, through which Cd upregulates MCU to enhance mitophagy and hepatotoxicity.
After cadmium (Cd) exposure, the cytosolic Ca2+‐dependent increases and activation of cAMP‐response element binding protein (CREB) orchestrally upregulates mitochondrial calcium uniporter (MCU) gene transcription, and promotes its translocation into mitochondria. The upregulated MCU in mitochondria directly interacts with voltage‐dependent anion‐selective channel protein 1 (VDAC1) and further enhances the dimerization and ubiquitination of VDAC1, which then overactivates mitophagy and leads to hepatocyte death.
Prokaryotic 16S ribosomal RNA (rRNA) sequences are widely used in environmental microbiology and molecular evolution as reliable markers for the taxonomic classification and phylogenetic analysis of ...microbes. Restricted by current sequencing techniques, the massive sequencing of 16S rRNA gene amplicons encompassing the full length of genes is not yet feasible. Thus, the selection of the most efficient hypervariable regions for phylogenetic analysis and taxonomic classification is still debated. In the present study, several bioinformatics tools were integrated to build an in silico pipeline to evaluate the phylogenetic sensitivity of the hypervariable regions compared with the corresponding full-length sequences.
The correlation of seven sub-regions was inferred from the geodesic distance, a parameter that is applied to quantitatively compare the topology of different phylogenetic trees constructed using the sequences from different sub-regions. The relationship between different sub-regions based on the geodesic distance indicated that V4-V6 were the most reliable regions for representing the full-length 16S rRNA sequences in the phylogenetic analysis of most bacterial phyla, while V2 and V8 were the least reliable regions.
Our results suggest that V4-V6 might be optimal sub-regions for the design of universal primers with superior phylogenetic resolution for bacterial phyla. A potential relationship between function and the evolution of 16S rRNA is also discussed.
Integration of CO2 capture capability from simulated flue gas and electrochemical CO2 reduction reaction (eCO2RR) active sites into a catalyst is a promising cost‐effective strategy for carbon ...neutrality, but is of great difficulty. Herein, combining the mixed gas breakthrough experiments and eCO2RR tests, we showed that an Ag12 cluster‐based metal–organic framework (1‐NH2, aka Ag12bpy‐NH2), simultaneously possessing CO2 capture sites as “CO2 relays” and eCO2RR active sites, can not only utilize its micropores to efficiently capture CO2 from simulated flue gas (CO2 : N2=15 : 85, at 298 K), but also catalyze eCO2RR of the adsorbed CO2 into CO with an ultra‐high CO2 conversion of 60 %. More importantly, its eCO2RR performance (a Faradaic efficiency (CO) of 96 % with a commercial current density of 120 mA cm−2 at a very low cell voltage of −2.3 V for 300 hours and the full‐cell energy conversion efficiency of 56 %) under simulated flue gas atmosphere is close to that under 100 % CO2 atmosphere, and higher than those of all reported catalysts at higher potentials under 100 % CO2 atmosphere. This work bridges the gap between CO2 enrichment/capture and eCO2RR.
Electrochemical CO2 reduction reaction occurs in the pores of a porous catalyst possessing CO2 capture sites, which boosts the catalytic performance virtually independent on the CO2 concentration.
This study aimed to establish an effective prognostic nomogram with or without plasma Epstein-Barr virus DNA (EBV DNA) for nondisseminated nasopharyngeal carcinoma (NPC).
The nomogram was based on a ...retrospective study of 4630 patients who underwent radiotherapy with or without chemotherapy at Sun Yat-sen University Cancer Center from 2007 to 2009. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index) and calibration curve and were compared with EBV DNA and the current staging system. The results were validated using bootstrap resampling and a prospective cohort study on 1819 patients consecutively enrolled from 2011 to 2012 at the same institution. All statistical tests were two-sided.
Independent factors derived from multivariable analysis of the primary cohort to predict recurrence were age, sex, body mass index (BMI), T stage, N stage, plasma EBV DNA, pretreatment high sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), and hemoglobin level (HGB), which were all assembled into the nomogram with (nomogram B) or without EBV DNA (nomogram A). The calibration curve for the probability of recurrence showed that the nomogram-based predictions were in good agreement with actual observations. The C-index of nomogram B for predicting recurrence was 0.728 (P < .001), which was statistically higher than the C-index values for nomogram A (0.690), EBV DNA (0.680), and the current staging system (0.609). The C-index of nomogram B (0.730) and nomogram A (0.681) remained higher for predicting recurrence among patients treated with intensity-modulated radiotherapy (P < .001). The results were confirmed in the validation cohort.
The proposed nomogram with or without plasma EBV DNA resulted in more accurate prognostic prediction for NPC patients.
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