Less is more: A minimalist “clickable” photo‐crosslinker (see scheme) was incorporated with numerous small‐molecule kinase inhibitors. The resulting probes were used for both in vitro (cell lysates) ...and in situ (live cells) proteome profiling, for large‐scale identification of their potential cellular kinase targets and shows improved outcomes over previous probes.
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.
Mergers of neutron stars are known to be associated with short γ-ray bursts
. If the neutron-star equation of state is sufficiently stiff (that is, the pressure increases sharply as the density ...increases), at least some such mergers will leave behind a supramassive or even a stable neutron star that spins rapidly with a strong magnetic field
(that is, a magnetar). Such a magnetar signature may have been observed in the form of the X-ray plateau that follows up to half of observed short γ-ray bursts
. However, it has been expected that some X-ray transients powered by binary neutron-star mergers may not be associated with a short γ-ray burst
. A fast X-ray transient (CDF-S XT1) was recently found to be associated with a faint host galaxy, the redshift of which is unknown
. Its X-ray and host-galaxy properties allow several possible explanations including a short γ-ray burst seen off-axis, a low-luminosity γ-ray burst at high redshift, or a tidal disruption event involving an intermediate-mass black hole and a white dwarf
. Here we report a second X-ray transient, CDF-S XT2, that is associated with a galaxy at redshift z = 0.738 (ref.
). The measured light curve is fully consistent with the X-ray transient being powered by a millisecond magnetar. More intriguingly, CDF-S XT2 lies in the outskirts of its star-forming host galaxy with a moderate offset from the galaxy centre, as short γ-ray bursts often do
. The estimated event-rate density of similar X-ray transients, when corrected to the local value, is consistent with the event-rate density of binary neutron-star mergers that is robustly inferred from the detection of the gravitational-wave event GW170817.
Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy ...(nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC).
Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596).
A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28, with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802).
NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.
•The CMISG1701 trial assessed the safety and efficacy of nCRT versus nCT followed by MIE for locally advanced bulky ESCC.•The nCRT followed by MIE strategy could not improve survival significantly compared with the nCT strategy.•The best strategy of neoadjuvant therapy for locally advanced bulky ESCC remains a pending issue.
To understand the impact of firework-burning (FW) particles on air quality and human health during the winter haze period, 39 elements, 10 water-soluble ions and 8 fractions of carbonaceous species ...in atmospheric PM2.5 in Nanjing were investigated during the 2014 Chinese Spring Festival (SF). Serious regional haze pollution persisted throughout the entire sampling period, with PM2.5 averaging at 113 plus or minus 69 mu g m-3 and visibility at 4.8 plus or minus 3.2 km. The holiday effect led to almost all the chemical species decreasing during the SF, except for Al, K, Ba and Sr which were related to FW. The source contributions of coal combustion, vehicle emission and road dust decreased dramatically, whereas FW contributed to about half of the PM2.5 during the SF period. The intensive emission of FW particles on New Year's Eve accounted for 60.1% of the PM2.5. Fireworks also obviously modified the chemical compositions of PM2.5, with 39.3% contributed by increased organic matter, followed by steadily increased loadings of secondary inorganic ions. The aging processes of the FW particles lasted for about 4 days reflected by the variations of Ba, Sr, NH super(+) sub(4), NO super(-) sub(3), SO sub(4) super(2-) and K super(+), characterized by heterogeneous reactions of SO sub(2) and NO sub(x) on crustal materials directly from FW, the replacement of Cl super(-) by NO super(-) sub(3) and SO sub(4) super(2-), coating of NO super(-) sub(3) and SO sub(4) super(2-) on soot, formation of secondary organic aerosols and metal-catalyzed formation of NO super(-) sub(3) and SO sub(4) super(2-) at higher relative humidity. During aging, the main contributors to the extinction coefficient shifted from elemental carbon and organic matter to ammonium sulfate. The particles raised higher cancer risk of 1.62 x 10 super(-6) by heavy metals (especially for Cd and As). This study provided detailed composition data and first comprehensive analysis of the aging processes of FW particles during the serious haze pollution period and their potential impact on human health.
The Wide Field-of-View Cherenkov Telescope Array (WFCTA) and the Water Cherenkov Detector Array (WCDA) of LHAASO are designed to work in combination for measuring the energy spectra of the cosmic ray ...species over a very wide energy range from a few TeV to 10 PeV. The energy calibration can be achieved with a proven technique of measuring the westward shift of the Moon shadow cast by galactic cosmic rays due to the geomagnetic field. This deflection angle Δ is inversely proportional to the cosmic ray rigidity. The precise measurement of the shifts by WCDA allows us to calibrate its energy scale for energies as high as 35 TeV. Through a set of commonly triggered events, the energy scales can be propagated to WFCTA. The energies of the events can be derived both by WCDA-1 and WFCTA with the median energies 23.4 ± 0.1 ± 1.3 TeV and ( 21.9 ± 0.1 TeV ), respectively, which are consistent within uncertainties. In addition, the propagation of the energy scale is also validated by the Moon shadow based on the same data selection criteria of the commonly triggered events. This paper reports, for the first time, an observational measurement of the absolute energy scale of the primary cosmic rays generating showers observed by air Cherenkov telescopes.
During insect larval–pupal metamorphosis, the obsolete larval organs and tissues undergo histolysis and programmed cell death to recycle cellular materials. It has been demonstrated that some ...cathepsins are essential for histolysis in larval tissues, but the process of tissue destruction is not well documented. Fat body, the homologous organ to mammalian liver and adipose tissue, goes through a distinct destruction process during larval–pupal transition. Herein, we found that most of the Bombyx proteases – including Bombyx cathepsin B (BmCatB) (BmCatLL-2), Bombyx cathepsin D (BmCatD), Bombyx cathepsin L like‐1 (BmCatLL-1) and –2(BmCatLL-2), Bombyx fibroinase (BmBcp), Bombyx matrix metalloprotease (BmMmp), Bombyx A disintegrin and metalloproteinase with thrombospondin motifs 1 (BmAdamTS‐1), Bombyx A disintegrin and metalloproteinase with thrombospondin motifs like (BmAdamTS L) and Bombyx cysteine protease inhibitor (Bmbcpi)– were expressed highly in fat body during feeding and metamorphosis, with a peak occurring during the nonfeeding moulting or prepupal stage, as well as being responsive to 20‐hydroxyecdysone (20E). The aforementioned protease genes expression was upregulated by injection of 20E into the feeding larvae, while blocking 20E signalling transduction led to downregulation. Western blotting and immunofluorescent staining of BmCatB and BmBcp confirmed the coincident variation of their messenger RNA (mRNA) and protein level during the development and after the treatments. Moreover, BmCatB, BmBcp, BmMmp and BmAdamTS‐1 RNA interference all led to blockage of larval fat body destruction. Taken together, we conclude that 20E regulates larval fat body destruction by upregulating related protease gene expression and protein levels during larval–pupal transition.
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