•It is currently uncertain whether people with diabetes are at higher risk of severe illness from coronavirus disease 2019 (COVID-19).•We found that diabetes was associated with an approximately ...4-fold increased risk of having severe/critical COVID-19 illness.•This association was independent of age, sex, obesity, hypertension and smoking.•These findings highlight the urgent need for a multidisciplinary team-based approach to management of this patient population.
Topological Weyl semimetal (TWS), a new state of quantum matter, has sparked enormous research interest recently. Possessing unique Weyl fermions in the bulk and Fermi arcs on the surface, TWSs offer ...a rare platform for realizing many exotic physical phenomena. TWSs can be classified into type-I that respect Lorentz symmetry and type-II that do not. Here, we directly visualize the electronic structure of MoTe
, a recently proposed type-II TWS. Using angle-resolved photoemission spectroscopy (ARPES), we unravel the unique surface Fermi arcs, in good agreement with our ab initio calculations that have nontrivial topological nature. Our work not only leads to new understandings of the unusual properties discovered in this family of compounds, but also allows for the further exploration of exotic properties and practical applications of type-II TWSs, as well as the interplay between superconductivity (MoTe
was discovered to be superconducting recently) and their topological order.
ABSTRACT
The High Energy (HE) X-ray telescope on board the Hard X-ray Modulation Telescope (Insight-HXMT) can serve as a wide field of view (FOV) gamma-ray monitor with high time resolution (μs) and ...large effective area (up to thousands cm2). We developed a pipeline to search for gamma-ray bursts (GRBs), using the traditional signal-to-noise ratio (SNR) method for blind search and the coherent search method for targeted search. By taking into account the location and spectrum of the burst and the detector response, the targeted coherent search is more powerful to unveil weak and sub-threshold bursts, especially those in temporal coincidence with gravitational wave (GW) events. Based on the original method in literature, we further improved the coherent search to filter out false triggers caused by spikes in light curves, which are commonly seen in gamma-ray instruments (e.g. Fermi/GBM, POLAR). We show that our improved targeted coherent search method could eliminate almost all false triggers caused by spikes. Based on the first two years of Insight-HXMT/HE data, our targeted search recovered 40 GRBs, which were detected by either Swift/BAT or Fermi/GBM but too weak to be found in our blind search. With this coherent search pipeline, the GRB detection sensitivity of Insight-HXMT/HE is increased to about 1.5E-08 erg cm−2 (200 keV–3 MeV). We also used this targeted coherent method to search Insight-HXMT/HE data for electromagnetic counterparts of LIGO-Virgo GW events (including O2 and O3a runs). However, we did not find any significant burst associated with GW events.
A
bstract
Using (10087 ± 44) × 10
6
J
/
ψ
events collected with the BESIII detector at the BEPCII
e
+
e
−
storage ring at the center-of-mass energy of
s
= 3.097 GeV, we present a search for the rare ...semi-muonic charmonium decay
J
/
ψ
→
D
−
μ
+
ν
μ
+ c.c.. Since no significant signal is observed, we set an upper limit of the branching fraction to be
B
(
J
/
ψ
→
D
−
μ
+
ν
μ
+ c.c.) < 5.6 × 10
−
7
at 90% confidence level. This is the first search for the weak decay of charmonium with a muon in the final state.
Myc oncoproteins are commonly upregulated in human cancers of different organ origins, stabilized by Aurora A, degraded through ubiquitin-proteasome pathway-mediated proteolysis, and exert oncogenic ...effects by modulating gene and protein expression. Histone deacetylases are emerging as targets for cancer therapy. Here we demonstrated that the class III histone deacetylase SIRT2 was upregulated by N-Myc in neuroblastoma cells and by c-Myc in pancreatic cancer cells, and that SIRT2 enhanced N-Myc and c-Myc protein stability and promoted cancer cell proliferation. Affymetrix gene array studies revealed that the gene most significantly repressed by SIRT2 was the ubiquitin-protein ligase NEDD4. Consistent with this finding, SIRT2 repressed NEDD4 gene expression by directly binding to the NEDD4 gene core promoter and deacetylating histone H4 lysine 16. Importantly, NEDD4 directly bound to Myc oncoproteins and targeted Myc oncoproteins for ubiquitination and degradation, and small-molecule SIRT2 inhibitors reactivated NEDD4 gene expression, reduced N-Myc and c-Myc protein expression, and suppressed neuroblastoma and pancreatic cancer cell proliferation. Additionally, SIRT2 upregulated and small-molecule SIRT2 inhibitors decreased Aurora A expression. Our data reveal a novel pathway critical for Myc oncoprotein stability, and provide important evidences for potential application of SIRT2 inhibitors for the prevention and therapy of Myc-induced malignancies.
A comprehensive microarray analysis of hepatocellular carcinoma (HCC) revealed distinct synexpression patterns during intrahepatic metastasis. Recent evidence has demonstrated that synexpression ...group member genes are likely to be regulated by master control gene(s). Here we investigate the functions and gene regulation of the transcription factor SOX4 in intrahepatic metastatic HCC. SOX4 is important in tumor metastasis as RNAi knockdown reduces tumor cell migration, invasion, in vivo tumorigenesis and metastasis. A multifaceted approach integrating gene profiling, binding site computation and empirical verification by chromatin immunoprecipitation and gene ablation refined the consensus SOX4 binding motif and identified 32 binding loci in 31 genes with high confidence. RNAi knockdown of two SOX4 target genes, neuropilin 1 and semaphorin 3C, drastically reduced cell migration activity in HCC cell lines suggesting that SOX4 exerts some of its action via regulation of these two downstream targets. The discovery of 31 previously unidentified targets expands our knowledge of how SOX4 modulates HCC progression and implies a range of novel SOX4 functions. This integrated approach sets a paradigm whereby a subset of member genes from a synexpression group can be regulated by one master control gene and this is exemplified by SOX4 and advanced HCC.
A
bstract
Based on
e
+
e
−
collision data collected at center-of-mass energies from 2.000 to 3.080 GeV by the BESIII detector at the BEPCII collider, a partial wave analysis is performed for the ...process
e
+
e
−
→
K
S
0
K
L
0
π
0
. The results allow the Born cross sections of the process
e
+
e
−
→
K
S
0
K
L
0
π
0
, as well as its subprocesses
e
+
e
−
→
K
∗
(892)
0
K
¯
0
and
K
2
∗
(1430)
0
K
¯
0
to be measured. The Born cross sections for
e
+
e
−
→
K
S
0
K
L
0
π
0
are consistent with previous measurements by BaBar, but with substantially improved precision. The Born cross section lineshape of the process
e
+
e
−
K
∗
(892)
0
K
¯
0
is consistent with a vector meson state around 2.2 GeV with a significance of 3.2
σ
. A Breit-Wigner fit determines its mass as
M
Y
= (2164
.
7
±
9
.
1
±
3
.
1) MeV
/c
2
and its width as Γ
Y
= (32
.
4
±
21
.
0
±
1
.
8) MeV.
There are few data on the molecular epidemiology of cryptococcosis in China. Here we investigated the species distribution, molecular types and antifungal susceptibilities of 312 Cryptococcus ...neoformans species complex isolates from ten hospitals over 5 years. Isolates were identified by internal transcribed spacer (ITS) sequencing and by two matrix-assisted laser desorption–ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems. Multilocus sequence typing (MLST) was used to verify species/variety and to designate molecular types. Susceptibility to six antifungal drugs was determined by the Sensititre YeastOne™ method. Cryptococcus neoformans was the predominant species (305/312 isolates (97.8%), all were ITS type 1, serotype A), of which 89.2% (272/305) were C. neoformans var. grubii MLST sequence type (ST) 5 and 6.2% (19/305) were ST31. Other C. neoformans var. grubii STs were rare but included six novel STs. Only two strains were C. neoformans var. neoformans (both serotype AD). Cryptococcus gattii was uncommon (n = 7, four ITS types) and comprised five MLST STs including one novel ST. For C. neoformans var. grubii, the proportion of isolates with non-wild-type MICs to fluconazole significantly rose in the fourth study year (from 0% (0/56 isolates) in the first year to 23.9% (17/71) in the fourth year), including five isolates with fluconazole MICs of ≥32 mg/L. The study has provided useful data on the species epidemiology and their genetic diversity and antifungal susceptibility. The proportional increase in isolates with non-wild-type MICs to fluconazole is noted.
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