Background Clinical research publications have become the dominant source and basis of clinical evidence-based decision-making. Exploring the type and quantity of clinical research publications in ...the PubMed database is useful for clarifying the changing trends of clinical research development in recent years. Therefore, a longitudinal analysis of the type and quantity of clinical research publications in the PubMed database over three decades was conducted. Methods The PubMed database was searched to retrieve clinical research according to the type and year of publication from January 1, 1991 to December 31, 2020. The research types were classified as primary and secondary literature. Results A total of 1,078,404 primary literatures were retrieved and the constituent proportions were ranked from high to low as case report/series (27.54%), randomized clinical trials (RCTs) (23.62%), cohort studies (21.05%), cross-sectional studies (17.49%), case control studies (9.15%), non-RCTs (1.01%), and pragmatic clinical trials (PCTs) (0.15%). Correspondingly, 1,302,173 secondary literatures were retrieved and ranked as narrative review (70.88%), systematic review (15.02%), systematic review and meta-analyses (13.89%), traditional meta-analyses (4.48%), expert consensus (2.31%), guidelines (1.49%), scoping reviews (0.68%), net meta-analyses (0.40%), and umbrella reviews (0.04%). The average annual growth rate for the primary literature was 10.28%, and ranked from high to low as PCTs (83.68%), cohort studies (17.74%), cross-sectional studies (17.61%), non-RCTs (12.11%), case control studies (8.86%), RCTs (7.68%), case report/series (7.51%); while that for the secondary literature was 10.57%, and ranked from high to low as net meta-analyses (48.97%), umbrella reviews (47.09%), scoping reviews (41.92%), systematic reviews and meta-analyses (33.44%), systematic reviews (33.05%), traditional meta-analyses (12.49%), expert consensuses (9.22%), narrative review (8.72%), and guidelines (2.82%). Conclusion Both the composition and number of clinical studies changed significantly from 1991 to 2020. Based on the trend, the case report/series, case control study, and narrative review are on the decline, while cohort study, cross-sectional study, systematic reviews, and systematic review and meta-analysis literature have increased. To improve the quality of clinical evidence, we recommend RCT and cohort study give priority to access to allocated research resources in future. Keywords: Data analysis, Clinical research, Literature summary, PubMed database, Longitudinal analysis
Mutations in a number of genes encoding mitochondrial aminoacyl-tRNA synthetases lead to non-syndromic and/or syndromic sensorineural hearing loss in humans, while their cellular and physiological ...pathology in cochlea has rarely been investigated
. In this study, we showed that histidyl-tRNA synthetase HARS2, whose deficiency is associated with Perrault syndrome 2 (PRLTS2), is robustly expressed in postnatal mouse cochlea including the outer and inner hair cells. Targeted knockout of
in mouse hair cells resulted in delayed onset (P30), rapidly progressive hearing loss similar to the PRLTS2 hearing phenotype. Significant hair cell loss was observed starting from P45 following elevated reactive oxygen species (ROS) level and activated mitochondrial apoptotic pathway. Despite of normal ribbon synapse formation, whole-cell patch clamp of the inner hair cells revealed reduced calcium influx and compromised sustained synaptic exocytosis prior to the hair cell loss at P30, consistent with the decreased supra-threshold wave I amplitudes of the auditory brainstem response. Starting from P14, increasing proportion of morphologically abnormal mitochondria was observed by transmission electron microscope, exhibiting swelling, deformation, loss of cristae and emergence of large intrinsic vacuoles that are associated with mitochondrial dysfunction. Though the mitochondrial abnormalities are more prominent in inner hair cells, it is the outer hair cells suffering more severe cell loss. Taken together, our results suggest that conditional knockout of
in mouse cochlear hair cells leads to accumulating mitochondrial dysfunction and ROS stress, triggers progressive hearing loss highlighted by hair cell synaptopathy and apoptosis, and is differentially perceived by inner and outer hair cells.
We develop an algorithm for predicting the arrival times of a transit vehicle at signalized intersections, with a focus on meeting the accuracy requirement associated with signal priority control ...applications. The algorithm uses both historical and real-time Global positioning system (GPS) vehicle location data. There are no data from other detectors, such as loops or cameras. The arrival time prediction is formulated as an optimal a posteriori parameter estimation problem, where the model is consisted of a historical model and an adaptive model that adaptively adjusts its filter gain based on real-time data. The estimates generated by these two models are fused in a weighted average derived from the solution of the parameter estimation problem. The prediction algorithm adaptively adjusts its weight distribution using error variances obtained from the two models. We include some simulations of field test results and their statistics to demonstrate the performance and convergence of the solution.
The surface energy budget over the Qinghai-Tibet Plateau (QTP) and the Arctic significantly influences the climate system with global consequences. The performances of 30 selected Coupled Model ...Intercomparison Project Phase 6 (CMIP6) models were evaluated based on six sites in the QTP and Arctic. The simulation results for latent heat flux (LE) were more accurate in the QTP, where the correlation coefficient and root mean square error (RMSE) were 0.9 and 30 W m
−2
, respectively. The results for sensible heat flux (H) were more accurate in the Arctic, the correlation coefficient and RMSE were 0.8 and 24 W m
−2
, respectively. Furthermore, the multiple models mean results revealed that the surface energy flux had seasonal variation and regional differences over the QTP and the Arctic. In the QTP, H was the lowest in winter, increased in spring, and reached the maximum in summer. However, the transitional changes in spring and autumn were not apparent in the Arctic, mainly due to seasonal net radiation difference between the two places. LE was affected by precipitation and surface soil moisture content. This work is important for understanding land-atmosphere interactions and useful for improving the accuracy of land surface models simulations.
Background
Adrenomyeloneuropathy (AMN) is a rare genetic disease. In this study, a case of AMN was uncovered in a Chinese family.
Methods
Clinical manifestations were collected and observed through ...medical records, physical examination, laboratory tests, and magnetic resonance imaging (MRI). Generation sequencing of the ABCD1 gene was performed, and the pedigree of the family was analyzed.
Results
The proband suffered from adrenocortical insufficiency at 8 years old and presented with a slowly progressive gait disorder at 21 years old. Physical examination, laboratory tests, and MRI showed that he had adult‐onset AMN manifestations, including spasticity and hyperactive tendon reflexes with Hoffman and Babinski signs in the limbs, difficulty in performing the heel‐to‐shin test, hyperpigmentation, increased levels of adrenocorticotropic hormone and very long‐chain fatty acids, decreased levels of corticosteroid and serum gesterol, and salient atrophy of the cervical and thoracic spinal cord. DNA analysis revealed a missense variant, c.290A>C (p.His97Pro) in exon 1 of the ABCD1 gene, in the proband. Sanger sequencing confirmed that the proband's mother was heterozygous for the same variant. The ABCD1 gene mutation transmitted in an X‐linked inheritance manner.
Conclusion
A novel missense mutation in the ABCD1 gene was identified in a Chinese family, which caused an unusual manifestation of adult‐onset AMN. This discovery is beneficial for the genetic counseling of patients with X‐linked adrenoleukodystrophy.
(a) We report a case of adrenomyeloneuropathy in a Chinese family. (b) DNA analysis revealed a missense variant c.290A>C (p.His97Pro) in exon 1 of the ABCD1 gene in the proband.
Key message
VcFLS
from
Vaccinium corymbosum
promoted myricetin biosynthesis in
Arabidopsis thaliana
and
VcFLS
expression was induced by salicylic acid.
Flavonoids are polyphenols with important ...functions in pigmentation, UV filtration, and symbiotic nitrogen fixation. Flavonols are a class of flavonoids that are produced by the desaturation of dihydroflavanols in a reaction that is catalyzed by flavonol synthase (FLS). In the study reported here, we cloned the full-length cDNA of
FLS
(designated as
VcFLS
) from
Vaccinium corymbosum
(blueberry) using rapid amplification of cDNA ends (RACE). The cDNA contained a 1005-bp open reading frame that encoded a 334-amino acid protein. Phylogenetic analysis showed that VcFLS was closely related to FaFLS, a flavonol synthase that catalyzed the formation of kaempferol and had little effect on the formation of quercetin. Quantitative RT-PCR analysis demonstrated that
VcFLS
was expressed in all of the tissues tested, with particularly high expression in the petals and young leaves (both green and red). The flavanols myricetin and quercetin also occurred in all of these tested tissues, with the highest levels detected in mature leaves. The expression of
VcFLS
was not consistent with the accumulation of quercetin and myricetin in different tissues, nor were the expressions of
VcFLS
,
VcPAL
,
VcCHS
,
VcF3H
, and
VcF3′5′H
consistent with the accumulation of the quercetin during fruit development. However, the change in the trend of
VcCHS
and
VcF3H
expression was similar with myricetin accumulation during fruit development. Expression profiling analysis revealed that
VcFLS
expression was induced by salicylic acid, a phytohormone involved in plant defense against pathogens, and was suppressed by gibberellic acid, a phytohormone involved in various aspects of plant development. Heterologous expression of
VcFLS
in
Arabidopsis thaliana
increased the content of myricetin, but did not affect quercetin content. Thus, we conclude that
VcFLS
is a key enzyme in the flavonol biosynthetic pathway and would appear to be involved in the plant defense response.
Background
Alterations of the trimethylation of histone 3 lysine 4 (H3K4me3) mark in monocytes are implicated in the development of autoimmune diseases. Therefore, the purpose of our study was to ...elucidate the role of H3K4me3‐mediated epigenetics in the pathogenesis of antiphospholipid syndrome (APS).
Methods
H3K4me3 Cleavage Under Targets and Tagmentation and Assay for Transposase‐Accessible Chromatin were performed to determine the epigenetic profiles. Luciferase reporter assay, RNA immunoprecipitation, RNA pull‐down, co‐immunoprecipitation and chromatin immunoprecipitation were performed for mechanistic studies. Transmission electron microscopy and propidium iodide staining confirmed cell pyroptosis. Primary monocytes from patients with primary APS (PAPS) and healthy donors were utilised to test the levels of key molecules. A mouse model mimicked APS was constructed with beta2‐glycoprotein I (β2GPI) injection. Blood velocity was detected using murine Doppler ultrasound.
Results
H3K4me3 signal and open chromatin at the ARID5B promoter were increased in an in vitro model of APS. The epigenetic factor ARID5B directly activated LINC01128 transcription at its promoter. LINC01128 promoted the formation of the BTF3/STAT3 complex to enhance STAT3 phosphorylation. Activated STAT3 interacted with the NLRP3 promoter and subsequently stimulated pyroptosis and apoptosis. ARID5B or BTF3 depletion compensated for LINC01128‐induced pyroptosis and apoptosis by inhibiting STAT3 phosphorylation. In mice with APS, β2GPI exposure elevated the levels of key proteins of pyroptosis and apoptosis pathways in bone marrow‐derived monocytes, reduced the blood velocity of the ascending aorta, increased the thrombus size of the carotid artery, and promoted the release of interleukin (IL)‐18, IL‐1β and tissue factor. Patients with PAPS had the high‐expressed ARID5B and LINC01128, especially those with triple positivity for antiphospholipid antibodies. Moreover, there was a positive correlation between ARID5B and LINC01128 expression.
Conclusion
This study indicated that ARID5B/LINC01128 was synergistically upregulated in APS, and they aggravated disease pathogenesis by enhancing the formation of the BTF3/STAT3 complex and boosting p‐STAT3‐mediated pyroptosis and apoptosis, thereby providing candidate therapeutic targets for APS.
Highlights
The H3K4me3 mark and chromatin accessibility at the ARID5B promoter are increased in vitro model mimicked APS.
ARID5B‐mediated LINC01128 induces pyroptosis and apoptosis via p‐STAT3 by binding to BTF3.
ARID5B is high‐ expressed in patients with primary APS and positively correlated with LINC01128 expression.
OICR‐9429 treatment mitigates pyroptosis and related inflammation in vivo and in vitro models mimicked APS.
This study demonstrates that the H3K4me3 mark and chromatin accessibility at the ARID5B promoter are increased in vitro model mimicked APS. ARID5B‐mediated LINC01128 induces pyroptosis and apoptosis via p‐STAT3 by binding to BTF3. ARID5B is high‐expressed in patients with primary APS and positively correlated with LINC01128 expression. OICR‐9429 treatment mitigates pyroptosis and related inflammation in vivo and in vitro models mimicked APS.
The realization of mid-infrared thermal radiation based on metamaterials insensitive to angle and polarization plays an important role in various thermal photonic applications. However, the ...challenges include the following: most previously designed thermal emitters usually contain metal components with unsatisfied physicochemical stability, accompanied with complex manufacturing technology. The present study proposes a mid-infrared thermal emitter at 3–6 μm wavelength range based on Fibonacci quasi-periodic structure, and a flat one-dimensional structure based on Fibonacci geometry resorting to ITO is designed. The proposed thermal emitter is, theoretically and experimentally, proven to possess good angular and polarization-independent selective thermal emission performance in a relatively wide infrared wavelength range. Furthermore, the good optical and high-temperature thermal stability of the designed thermal emitter is verified in the present experimental research. The thermal emitters proposed have advantages in polarization-independence without scale restraint and low cost but with wide vision. In summary, the present study provides a new tactics for obtaining non-metal spectral selective thermal emitters in a relatively wide wavelength range and thermal photonic applications under harsh conditions.
Lalin River is a first-level tributary of the right bank of Songhua River. High-quality corn production bases irrigated by the Lalin River are famous throughout the country. However, in the last few ...decades, the hydrological regimes changed severely due to expansion of the irrigation area, leading to more water used for irrigation. To investigate the variation of the hydrological situation, we analyzed the daily runoff data at the Caijiagou Hydrological Station from 1954 to 2015 by using the Indicators of Hydrologic Alteration (IHA) and the range of variability approach (RVA). The results showed a severe decreasing trend of the average monthly flow during the water level with regular and high periods, with a negative slope of −2.924 in August and −2.518 in September. The increasing trend of low pulse and fall rate of flow and the decreasing trend of the rising rate of flow demonstrate that water resources are drying up. Regarding the flow rate, the annual maximum value decreased significantly in slopes of −7.9, −7.6, −6.09, −5.28, and −2.98 on the 1-day, 3-day, 7-day, 30-day, and 90-day, respectively. The flow reversals’ average value is 65 to 50 times/year from 1954 to 2015. From RVA analysis, the hydrological alteration of the basin decreased 50% after 1978. To investigate the influencing factors for the hydrological alteration, we analyzed the variation in land cover and land use between 1978 and 2015. The results showed that the area of paddy fields in 2015 was 1.5 times that of 1978, and the water consumption in paddy fields accounts for 80.8% of the total water resources. Consequently, the wetland area of the basin in 2015 was only 53% of 1978, and the wetland area of the two wetland nature reserves at the mouth of the Lalin River in 2015 was about 53% of 1978. Furthermore, the meteorological condition in the LRB shows a warming and drying tendency. The air temperature has shown an intensively increased tendency, and precipitation decreased in the last 50 years. This indicates that the hydrological situation in the Lalin River Basin has changed considerably under the dual influence of human activities and global warming.
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