Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the ...efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC.
Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib 50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle). The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety.
A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028. The median PFS was 18.0 months in the toripalimab–axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab–axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab–axitinib group and 58.6% of patients in the sunitinib group.
In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile
ClinicalTrials.gov NCT04394975
•Toripalimab plus axitinib provided significantly better PFS than sunitinib as a first-line treatment for advanced RCC.•A significantly higher ORR was found in patients who received toripalimab plus axitinib than those who received sunitinib.•The combination of toripalimab plus axitinib was generally well tolerated.•No new safety signals were identified in the combination outside the known safety profile of toripalimab or axitinib.
•MSTN−/− pigs subcutaneous adipose tissue clearly showed characteristic multilocular lipid droplets like beige adipose in contrast to the tissues from WT pigs.•MSTN gene deletion in adipose tissue ...activates the browning of white fat via the AMPK signaling pathway.•MSTN−/− skeletal muscle secretes IL-6 and modulates the AMPK pathway in adipocytes, and induces white adipose conversion into beige adipose in pigs.
Myostatin (MSTN) is primarily expressed in skeletal muscle and plays an important role in the regulation of muscle growth and development as well as fat deposition; however, little is known about the molecular mechanism through which MSTN regulates body fat deposition. Therefore, in this study, we sought to identify the signaling pathways through which MSTN regulates fat accumulation in pigs. MSTN knockout (MSTN−/−) pigs showed increased muscle mass, decreased fat mass, and a leaner body composition. In this study, we found that the adipose tissue of MSTN−/− pigs exhibits the characteristics of beige adipose tissue, and the mRNA expression levels of beige adipose marker genes, including UCP3, Cidea, and CD137, were significantly increased. Remarkably, the observed beige phenotype was not adipocyte autonomous but rather caused by muscle-secreted myokine interleukin (IL)-6. This occurrence results in increased AMP-activated protein kinase (AMPK) phosphorylation in adipose tissue, which subsequently activates peroxisome proliferator-activated receptor gamma coactivator 1α and the conversion of white adipocytes to beige in pigs. Therefore, we concluded that MSTN deficiency leads to increased IL-6 secretion in skeletal muscle and activates AMPK in adipocytes, thereby increasing the beige adipose tissue in MSTN−/− pigs.
Summary
Background
Tinea capitis is still common in developing countries, such as China. Its pathogen spectrum varies across regions and changes over time.
Objectives
This study aimed to clarify the ...current epidemiological characteristics and pathogen spectrum of tinea capitis in China.
Methods
A multicentre, prospective descriptive study involving 29 tertiary hospitals in China was conducted. From August 2019 to July 2020, 611 patients with tinea capitis were enrolled. Data concerning demography, risk factors and fungal tests were collected. When necessary, the pathogens were further identified by morphology or molecular sequencing in the central laboratory.
Results
Among all enrolled patients, 74·1% of the cases were in patients aged 2–8 years. The children with tinea capitis were mainly boys (56·2%) and were more likely than adults to have a history of animal contact (57·4% vs. 35·3%, P = 0·012) and zoophilic dermatophyte infection (73·5% vs. 47%). The adults were mainly female (83%) and were more likely than children to have anthropophilic agent infection (53% vs. 23·9%). The most common pathogen was zoophilic Microsporum canis (354, 65·2%), followed by anthropophilic Trichophyton violaceum (74, 13·6%). In contrast to the eastern, western and northeastern regions, where zoophilic M. canis predominated, anthropophilic T. violaceum predominated in central China (69%, P < 0·001), where the patients had the most tinea at other sites (20%) and dermatophytosis contact (26%) but the least animal contact (39%). Microsporum ferrugineum was the most common anthropophilic agent in the western area, especially in Xinjiang province.
Conclusions
Boys aged approximately 5 years were the most commonly affected group. Dermatologists are advised to pay more attention to the different transmission routes and pathogen spectra in different age groups from different regions.
What is already known about this topic?
Tinea capitis is an infection of the scalp and hair caused by dermatophytes and is still common in developing countries. Prepubertal children are mainly affected.
The pathogen spectrum of tinea capitis varies across different geographical areas and changes over time.
Nationwide prospective epidemiological surveys of tinea capitis in China are rare and out of date.
What does this study add?
This study provides data concerning the epidemiological characteristics and pathogen spectrum of tinea capitis in contemporary China.
Boys aged approximately 5 years were most commonly affected and were more likely than adults to have zoophilic dermatophyte infection.
The main pathogens of tinea capitis in China are zoophilic dermatophytes, mainly Microsporum canis. In contrast to the other regions, the predominant pathogens in central China are anthropophilic dermatophytes.
Plain language summary available online
Concentrations of elemental carbon (EC) were measured in a 150 yr sediment record collected from Lake Chaohu in Anhui Province, eastern China, using three different thermal analytical methods: ...IMPROVE_A thermal optical reflectance (TOR), STN_thermal optical transmittance (TOT), and chemothermal oxidation (CTO). Distribution patterns for EC concentrations are different among the three methods, most likely due to the operational definition of EC and different temperature treatments prescribed for each method. However, similar profiles were found for high-temperature EC fractions among different methods. Historical soot(TOR) (high-temperature EC fractions measured by the IMPROVE_A TOR method) from Lake Chaohu exhibited stable low concentrations prior to the late 1970s and a sharp increase thereafter, corresponding well with the rapid industrialization of China in the last three decades. This may suggest that high-temperature thermal protocols are suitable for differentiating between soot and other carbon fractions. A similar soot(TOR) record was also obtained from Lake Taihu (~200 km away), suggesting a regional source of soot. The ratio of char(TOR) (low-temperature EC fraction measured by the IMPROVE_A TOR method, after correction for pyrolysis) to soot(TOR) in Lake Chaohu shows an overall decreasing trend, consistent with gradual changes in fuel use from wood burning to increasing fossil fuel combustions. Average higher char(TOR)/soot(TOR) was observed in Lake Taihu than in Lake Chaohu in the past 150 years, consistent with the longer and more extensive industrialization around the Taihu region.
HUBS: Hot Universe Baryon Surveyor Cui, W.; Chen, L.-B.; Gao, B. ...
Journal of low temperature physics,
04/2020, Letnik:
199, Številka:
1-2
Journal Article
Recenzirano
Hot Universe Baryon Surveyor (HUBS) is proposed in China as a major X-ray mission for the next decade. It is designed to be highly focused scientifically, with two primary objectives: (1) detecting ...X-ray emission from hot baryons in intergalactic medium and circumgalactic medium (CGM), and characterizing their physical and chemical properties; (2) studying, based on the observations, the accretion and feedback processes that are thought to be highly relevant to the heating and chemical enrichment of the baryons in the CGM. Because of very low densities, the signal is expected to be very weak and thus technically difficult to detect. On the other hand, the spectrum of the emission is expected to be line rich, so it would be effective for detecting the hot baryons in bright emission lines. For that, an instrument with high spectral resolution, large effective area and large field of view (FoV) would be required. HUBS will couple a TES-based X-ray imaging spectrometer to a large FoV X-ray telescope to satisfy these requirements. A preliminary design of HUBS is presented.
Periodic mesoporous organosilica magnetic hollow spheres (PMO–MHS) are synthesized. The particle size, shell wall thickness and saturation magnetization value of PMO–MHS are tunable by varying the ...ratio of templating agent to magnetic nanoparticles. The high saturation magnetization ensures that these functional mesoporous hollow spheres can be efficient materials for targeted drug delivery assisted by magnetic fields.
A series of Ni-free Zr55Ti3HfxCu32-xAl10 (x = 0, 1, 2, 3, 4, 5 at. %) bulk metallic glasses (BMGs) were developed by copper mold suction-casting. The effect of partially substituting Cu by Hf was ...investigated in terms of glass-forming ability (GFA), mechanical properties, and corrosion behavior. As a result of the partial substitution, the GFA of Hf-bearing amorphous alloys were significantly enhanced as compared to Zr55Ti3Cu32Al10 BMGs. Hf addition also enlarged the supercooled liquid region from 55 K to 70 K. The critical diameter was found to increase from 4 mm to 8 mm for x = 3. The corresponding compressive yield strength was over 1800 ± 21 MPa with a large plastic strain above 2.60 ± 0.10%. Electrochemical tests indicated that the lowest corrosion current density was 1.6 ± 0.1 × 10−8 A/cm2 for the alloy with x = 5 in H2SO4 solution, thereby yielding a superior corrosion resistance.
•Partial substitution of Hf with Cu greatly enhanced the GFA of BMGs.•The Hf-bearing BMGs show a higher σy of 1800 ± 21 MPa and a large εp of 2.60 ± 0.10%.•The lowest icorr of BMGs is 1.6 ± 0.1 × 10−8 A/cm2 in H2SO4 solution.
Elemental carbon (EC) and polycyclic aromatic compounds (PACs) are potential proxies for the reconstruction of change in human activities and the origin of air masses in historic times. In this ...study, the historic deposition of char and soot (the two subtypes of EC) and PACs in a 150-year sediment core from different topographic subbasins of Lake Qinghai on the Qinghai Tibetan Plateau (QTP) were reconstructed. The objective was to explore how the variations in the concentrations of EC and PACs, in the ratios of char to soot and of oxygenated polycyclic aromatic hydrocarbons (OPAHs) to parent PAHs, and in the composition of the PAC mixtures reflect historical changes in climate and human activity and the origin of air masses arriving at the QTP. The deposition fluxes of soot in the different subbasins were similar, averaging 0.18 (range of 0.15-0.25) and 0.16 (0.13-0.23) g m(-2) year(-1), respectively, but they varied for char (averaging 0.11 and 0.22 g m(-2) year(-1), respectively), suggesting ubiquitous atmospheric deposition of soot and local river inputs of char. The different vertical distributions of the char/soot ratios in the different subbasins can be interpreted in terms of the different transport mechanisms of char and soot. An abrupt increase in soot concentrations since 1980 coincides with results from the QTP ice cores that were interpreted to be indicative of soot transport from South Asia. Similar concentration patterns of PAHs with soot and 9,10-anthraquinone/anthracene (9,10-AQ/ANT) ratios all >2.0 suggest regional PAC sources. Increasing PAH/soot ratios and decreasing 9,10-AQ/ANT ratios since the beginning of the 1970s indicate increasing local emissions. The historical trends of these diagnostic ratios indicate an increase in the fossil-fuel contribution since the beginning of the 1970s. The increase of perylene concentrations with increasing core depth and the ratio of perylene to its penta-aromatic isomers indicate that perylene originates mainly from in situ biogenic diagenesis. We demonstrate that the concentrations of EC, char, soot, and PACs in sediments can be used to reconstruct local, regional, and remote sources and transport pathways of pollutants to the QTP.
A
bstract
We present measurements of the branching fractions for the decays
B
→
Kμ
+
μ
−
and
B
→
Ke
+
e
−
, and their ratio (
R
K
), using a data sample of 711 fb
−
1
that contains 772 × 10
6
B
B
¯
...events. The data were collected at the ϒ(4
S
) resonance with the Belle detector at the KEKB asymmetric-energy
e
+
e
−
collider. The ratio
R
K
is measured in five bins of dilepton invariant-mass-squared (
q
2
):
q
2
∈ (0
.
1
,
4
.
0)
,
(4
.
00
,
8
.
12)
,
(1
.
0
,
6
.
0), (10
.
2
,
12
.
8) and (
>
14
.
18) GeV
2
/c
4
, along with the whole
q
2
region. The
R
K
value for
q
2
∈ (1
.
0
,
6
.
0) GeV
2
/c
4
is
1.03
−
0.24
+
0.28
± 0
.
01. The first and second uncertainties listed are statistical and systematic, respectively. All results for
R
K
are consistent with Standard Model predictions. We also measure
CP
-averaged isospin asymmetries in the same
q
2
bins. The results are consistent with a null asymmetry, with the largest difference of 2.6 standard deviations occurring for the
q
2
∈ (1
.
0
,
6
.
0) GeV
2
/c
4
bin in the mode with muon final states. The measured differential branching fractions,
d
ℬ
/dq
2
, are consistent with theoretical predictions for charged
B
decays, while the corresponding values are below the expectations for neutral
B
decays. We have also searched for lepton-flavor-violating
B
→
Kμ
±
e
∓
decays and set 90% confidence-level upper limits on the branching fraction in the range of 10
−
8
for
B
+
→
K
+
μ
±
e
∓
, and
B
0
→
K
0
μ
±
e
∓
modes.
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