Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

Probing dark matter particles from evaporating primordial black holes via electron scattering in the CDEX-10 experiment

Dark matter(DM)is a major constituent of the Universe.However,no definite evidence of DM particles(denoted as“χ”)has been found in DM direct detection(DD)experiments to date.There is a novel concept of detectingχfrom evaporating primordial black holes(PBHs).We search forχemitted from PBHs by investigating their interaction with target electrons.The examined PBH masses range from 1×10^(15)to 7×10^(16)g under the current limits of PBH abundance fPBH.Using 205.4 kg·day data obtained from the CDEX-10 experiment conducted in the China Jinping Underground Laboratory,we exclude theχ-electron(χ-e)elastic-scattering cross sectionσ_(χe)~5×10^(-29)cm^(2)forχwith a mass■keV from our results.With the higher radiation background but lower energy threshold(160 eV),CDEX-10 fills a part of the gap in the previous work.If(m_(χ),σ_(χe))can be determined in the future,DD experiments are expected to impose strong constraints on fPBHfor large MPBHs.

Mertk Reduces Blood-Spinal Cord Barrier Permeability Through the Rhoa/Rock1/P-MLC Pathway After Spinal Cord Injury

Disruption of the blood-spinal cord barrier(BSCB)is a critical event in the secondary injury following spinal cord injury(SCI).Mertk has been reported to play an important role in regulating inflammation and cytoskeletal dynamics.However,the specific involvement of Mertk in BSCB remains elusive.Here,we demonstrated a distinct role of Mertk in the repair of BSCB.Mertk expression is decreased in endothelial cells following SCI.Overexpression of Mertk upregulated tight junction proteins(TJs),reducing BSCB permeability and subsequently inhibiting inflammation and apoptosis.Ultimately,this led to enhanced neural regeneration and functional recovery.Further experiments revealed that the RhoA/Rock1/P-MLC pathway plays a key role in the effects of Mertk.These findings highlight the role of Mertk in promoting SCI recovery through its ability to mitigate BSCB permeability and may provide potential targets for SCI repair.

Study on cosmogenic activation in germanium detectors for future tonne-scale CDEX experiment

A study on cosmogenic activation in germanium was carried out to evaluate the cosmogenic background level of natural and ^(70)Ge depleted germanium detectors. The production rates of long-lived radionuclides were calculated with Geant4 and CRY.Results were validated by comparing the simulated and experimental spectra of CDEX-1B detector. Based on the validated codes, the cosmogenic background level was predicted for further tonne-scale CDEX experiment. The suppression of cosmogenic background level could be achieved by underground germanium crystal growth and high-purity germanium detector fabrication to reach the sensitivity requirement for direct detection of dark matter. With the low cosmogenic background, new physics channels,such as solar neutrino research and neutrinoless double-beta decay experiments, were opened and the corresponding simulations and evaluations were carried out.

First results on ^(76)Ge neutrinoless double beta decay from CDEX-1 experiment

We report the first results on 76Ge neutrinoless double beta decay from stage one of the China dark-matter experiment （CDEX）. A p-type point-contact high-purity germanium detector with a mass of 994g has been installed to detect neutrinoless double beta decay events, as well as to directly detect dark matter particles. An exposure of 304kgd has been analyzed over a wide spectral band from 500keV to 3MeV. The average event rate obtained was about 0.012 counts per keV per kg per day over the 2.039MeV energy range. The half-life of76Ge neutrinoless double beta decay derived based on this result is 70v2〉6.4× 1022 yr （90%C.L.）. An upper limit on the effective Majorana-neutrino mass of 5.0eV has been achieved.

First experimental constraints on WIMP couplings in the effective field theory framework from CDEX

We present weakly interacting massive particles(WIMPs) search results performed using two approaches of effective field theory from the China Dark Matter Experiment(CDEX), based on the data from both CDEX-1B and CDEX-10 stages. In the nonrelativistic effective field theory approach, both time-integrated and annual modulation analyses were used to set new limits for the coupling of WIMP-nucleon effective operators at 90% confidence level(C.L.) and improve over the current bounds in the low mχregion. In the chiral effective field theory approach, data from CDEX-10 were used to set an upper limit on WIMP-pion coupling at 90% C.L. We for the first time extended the limit to the m_(χ)<6 GeV/c^(2) region.