Our understanding of when and how humans adapted to living on the Tibetan Plateau at altitudes above 2000 to 3000 meters has been constrained by a paucity of archaeological data. Here we report data ...sets from the northeastern Tibetan Plateau indicating that the first villages were established only by 5200 calendar years before the present (cal yr B.P.). Using these data, we tested the hypothesis that a novel agropastoral economy facilitated year-round living at higher altitudes since 3600 cal yr B.P. This successful subsistence strategy facilitated the adaptation of farmers-herders to the challenges of global temperature decline during the late Holocene.
The prevalence of diabetes in China is among the highest in the world. For this reason, findings from the 2016 Global Burden of Disease (GBD) study were used to calculate the burden of hyperglycaemia ...and diabetes in China.
Following the general analytical strategy used in GBD 2016, diabetes prevalence and mortality were analyzed by age and gender. Trends in disability-adjusted life years (DALYs) due to diabetes were assessed in 33 province-level administrative units from 1990 to 2016, and similar data were provided for chronic kidney disease (CKD) related to diabetes and, as an overall summarizing measure, for hyperglycaemia expressed as high fasting plasma glucose (HFPG).
From 1990 to 2016, all-age prevalence of diabetes rose from 3.7% to 6.6%, and all-age diabetes and diabetes-related CKD mortality rates increased by 63.5% and 33.3%, respectively, with both rates increasing more rapidly in diabetes patients aged 15–49 years than in any other age groups. In 2016, HFPG became China's sixth leading cause of DALYs, and the attributable DALYs burden was 1802.3/100,000 population. Although the number of diabetes DALYs increased by 95% from 1990 to 2016, age-standardized diabetes DALYs rates increased by only 2.3%. Also, from 1990 to 2016, rates of age-standardized DALYs due to diabetes decreased in 14 provinces, but increased in 19 provinces. High BMI Scores and diets low in whole grains, nuts and seeds were the most important risk factors for diabetes in 2016.
Diabetes and hyperglycaemia constitute a huge health burden in China. The substantial increase in diabetes-related burden represents an ongoing challenge, given the rapidly ageing Chinese population. Thus, a targeted control and preventative strategy needs to be developed at risk factor level to reduce this burden.
Summary
Background
Various trials have been conducted on the management of male pattern hair loss (MPHL), but the outcomes often seem to be limited. Adjuvant therapies are urgently needed.
Aim
To ...evaluate the efficacy and safety of combined fractional radiofrequency microneedling (FRM) and 5% topical minoxidil in the treatment of male pattern hair loss.
Methods
In total, 19 Chinese men were enrolled in this randomized, controlled, split‐scalp trial. Participants received monotherapy with 5% topical minoxidil twice daily to one half of the scalp, while on the other half of the scalp the treatment with twice‐daily 5% topical minoxidil was combined with five sessions of FRM at 4‐week intervals. Mean hair count and hair thickness, global assessment by the investigators, subject self‐assessment and adverse effects were assessed.
Results
After 5 months of treatment, mean hair count increased from 44.12 ± 21.58 to 73.14 ± 25.45 on the combined‐therapy side and from 46.22 ± 18.77 to 63.21 ± 19.22 on the monotherapy side, while mean hair thickness increased from 53 ± 13 μm to 71 ± 15 μm and from 52 ± 16 μm to 66 ± 14 μm, respectively. Compared with the monotherapy side, the combined‐therapy side had a higher degree of improvement in both hair count (P = 0.01) and hair thickness (P = 0.02).
Conclusions
Combined treatment with fractional radiofrequency microneedle and 5% topical minoxidil could be an effective and safe treatment option for male pattern hair loss.
In order to address the present difficulty in experimentally generating the relativistic Laguerre-Gaussian laser, primarily due to damage caused to optical modulators, a high-reflectivity phase ...mirror is applied in the femtosecond petawatt laser system to generate a relativistic hollow laser at the highest intensity of 6.3 × 1019 W / cm2 for the first time. A simple optical model is used to verify that the vortex laser may be generated in this new scheme; using such a relativistic vortex laser, the hollow plasma drill and acceleration are achieved experimentally and proven by particle-in-cell simulations. With the development of the petawatt laser, this scheme opens up possibilities for the convenient production of the relativistic hollow laser at high repetition and possible hollow plasma acceleration, which is important for a wide range of applications such as the generation of radiation sources with orbital angular momentum, fast ignition for inertial confinement fusion, and jet research in the astrophysical environment.
This is the second installment for the Large Sky Area Multi-Object Fibre Spectroscopic Telescope (LAMOST) Quasar Survey, which includes quasars observed from 2013 September to 2015 June. There are ...9024 confirmed quasars in DR2 and 10911 in DR3. After cross-match with the Sloan Digital Sky Survey (SDSS) quasar catalogs and NED, 12126 quasars are discovered independently. Among them, 2225 quasars were released by SDSS DR12 QSO catalog in 2014 after we finalized the survey candidates. 1801 sources were identified by SDSS DR14 as QSOs. The remaining 8100 quasars are considered as newly founded, and among them, 6887 quasars can be given reliable emission line measurements and the estimated black hole masses. Quasars found in LAMOST are mostly located at low-to-moderate redshifts, with a mean value of 1.5. The highest redshift observed in DR2 and DR3 is 5. We applied emission line measurements to H , Hβ, Mg ii, and C iv. We deduced the monochromatic continuum luminosities using photometry data, and estimated the virial black hole masses for the newly discovered quasars. Results are compiled into a quasar catalog, which will be available online.
Exosomes are nanosized membrane vesicles released from cells after fusion of multivesicular bodies (MVBs) with the plasma membrane (PM) and play important roles in intercellular communication and ...numerous biological processes. However, the molecular mechanisms regulating exosome secretion remain poorly understood. Here we identify KIBRA as an adaptor-like protein that stabilizes Rab27a, which in turn controls exosome secretion both in vitro and in vivo. Knockdown or overexpression of KIBRA in neuronal and podocyte cell lines leads to a decrease or increase of exosome secretion, respectively, and KIBRA depletion increases MVB size and number. Comparing protein profiles between KIBRA knockout and wild-type mouse brain showed significantly decreased Rab27a, a small GTPase that regulates MVB-PM docking. Rab27a is stabilized by interacting with KIBRA, which prevents ubiquitination and degradation via the ubiquitin-proteasome pathway. In conclusion, we show that KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a.
Abstract
As one of the major abiotic stresses restricting the development of global agriculture, saline–alkali stress causes osmotic stress, ion poisoning, ROS damage and high pH damage, which ...seriously restrict sustainable development of fruit industry. Therefore, it is essential to develop and cultivate saline–alkali‐resistant apple rootstocks to improve the yield and quality of apples in China.
Based on transcriptome data,
MhANR
(LOC114827797), which is significantly induced by saline–alkali stress, was cloned from
Malus halliana
. The physicochemical properties, evolutionary relationships and
cis
‐acting elements were analysed. Subsequently, the tolerance of
MhANR
overexpression in
Arabidopsis thaliana
, tobacco, and apple calli to saline–alkali stress was verified through genetic transformation.
Transgenic plants contained less Chl
a
, Chl
b
and proline, SOD, POD and CAT activity, and higher relative electrical conductivity (REC) compared to WT plants under saline–alkali stress. In addition, expression of saline–alkali stress‐related genes in overexpressed apple calli were also lower than in WT calli, including the antioxidant genes (
MhSOD
and
MhCAT
^), the Na
+
transporter genes (
MhCAX5
,
MhCAX5
,
MhSOS1
,
MhALT1
), and the H
+
‐ATPase genes (
MhAHA2
and
MhAHA8
), while expression of the K
+
transporter genes (
MhSKOR
and
MhNHX4
) were higher.
Expression of
MhANR
reduced tolerance of
A. thaliana
, tobacco, and apple calli to saline–alkali stress by regulating osmoregulatory substances, chlorophyll content, antioxidant enzyme activity, and expression of saline–alkali stress‐related genes. This research provides a theoretical basis for cultivating apple rootstocks with effective saline–alkali stress tolerance.
Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in malignant tumors and has important roles in multiple aspects of cancer aggressiveness. Thus targeting STAT3 ...promises to be an attractive strategy for treatment of advanced metastatic tumors. Although many STAT3 inhibitors targeting the SH2 domain have been reported, few have moved into clinical trials. Targeting the DNA-binding domain (DBD) of STAT3, however, has been avoided due to its 'undruggable' nature and potentially limited selectivity. In a previous study, we reported an improved in silico approach targeting the DBD of STAT3 that resulted in a small-molecule STAT3 inhibitor (inS3-54). Further studies, however, showed that inS3-54 has off-target effect although it is selective to STAT3 over STAT1. In this study, we describe an extensive structure and activity-guided hit optimization and mechanistic characterization effort, which led to identification of an improved lead compound (inS3-54A18) with increased specificity and pharmacological properties. InS3-54A18 not only binds directly to the DBD and inhibits the DNA-binding activity of STAT3 both in vitro and in situ but also effectively inhibits the constitutive and interleukin-6-stimulated expression of STAT3 downstream target genes. InS3-54A18 is completely soluble in an oral formulation and effectively inhibits lung xenograft tumor growth and metastasis with little adverse effect on animals. Thus inS3-54A18 may serve as a potential candidate for further development as anticancer therapeutics targeting the DBD of human STAT3 and DBD of transcription factors may not be 'undruggable' as previously thought.
The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This ...work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2
/
years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.
A homo-dinuclear Cu(II) complex Cu
2
(L)
2
with the stoichiometric ratio of Cu(II) : (L)
2–
= 2 : 2 was synthesized by the reaction of the ligand ...(4-methyl-6-aldehyde-6′-methoxy-2,2′-ethylenediyldioxybis(nitrilomethylidyne)diphenol) with Cu(OAc)
2
·H
2
O in the mixed CH
2
Cl
2
–MeOMe–EtOH solution (an unexpected ligand is the intermediate of condensation reaction of starting ligand with acetone). The Cu(II) complex was characterized by elemental analysis, IR, UV-Vis and X-ray crystallography. The Cu(II) complex crystallizes in monoclinic space group
P
2
1
/
n
and consists of two Cu(II) atoms and two completely deprotonated ligand (L)
2–
units. Through the analysis of intermolecular interactions, the Cu(II) complex units can form a 2D supramolecular structure through intermolecular hydrogen bonds and C–H···π interactions, respectively, meanwhile, the molecular interactions were quantitatively studied by Hirshfeld surfaces analyses. The fluorescence properties and DFT calculations were performed.
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