Abstract
Using the JVLA, we explored the Galactic center (GC) with a resolution of 0.″05 at 33.0 and 44.6 GHz. We detected 64 hypercompact radio sources (HCRs) in the central parsec. The dense group ...of HCRs can be divided into three spectral types: 38 steep-spectrum (
α
≤ −0.5) sources, 10 flat-spectrum (−0.5 <
α
≤ 0.2) sources, and 17 inverted-spectrum sources having
α
> 0.2, assuming
S
∝
ν
α
. The steep-spectrum HCRs are likely to represent a population of massive stellar remnants associated with nonthermal compact radio sources powered by neutron stars and stellar black holes. The surface-density distribution of the HCRs as a function of radial distance (
R
) from Sgr A* can be described as a steep power law Σ(
R
) ∝
R
−Γ
, with Γ = 1.6 ± 0.2, along with the presence of a localized order-of-magnitude enhancement in the range 0.1–0.3 pc. The steeper profile of the HCRs relative to that of the central cluster might result from the concentration of massive stellar remnants by mass segregation at the GC. The GC magnetar SGR J1745−2900 belongs to the inverted-spectrum subsample. We find two spectral components present in the averaged radio spectrum of SGR J1745−2900, separated at
ν
∼ 30 GHz. The centimeter component is fitted to a power law with
α
cm
= −1.5 ± 0.6. The enhanced millimeter component shows a rising spectrum
α
mm
= 1.1 ± 0.2. Based on the ALMA observations at 225 GHz, we find that the GC magnetar is highly variable on a day-to-day timescale, showing variations up to a factor of 6. Further JVLA and ALMA observations of the variability, spectrum, and polarization of the HCRs are critical for determining whether they are associated with stellar remnants.
Triclosan 5-chloro-2-(2,4-dichlorophenoxy) phenol, TCS, a common antimicrobial additive in many personal care and health care products, is frequently detected in human blood and urine. Therefore, it ...has been considered an emerging and potentially toxic pollutant in recent years. Long-term exposure to TCS has been suggested to exert endocrine disruption effects, and promote liver fibrogenesis and tumorigenesis. This study was aimed at clarifying the underlying cellular and molecular mechanisms of hepatotoxicity effect of TCS at the initiation stage.
C57BL/6 mice were exposed to different dosages of TCS for 2 weeks and the organ toxicity was evaluated by various measurements including complete blood count, histological analysis and TCS quantification. Single cell RNA sequencing (scRNA-seq) was then carried out on TCS- or mock-treated mouse livers to delineate the TCS-induced hepatotoxicity. The acquired single-cell transcriptomic data were analyzed from different aspects including differential gene expression, transcription factor (TF) regulatory network, pseudotime trajectory, and cellular communication, to systematically dissect the molecular and cellular events after TCS exposure. To verify the TCS-induced liver fibrosis, the expression levels of key fibrogenic proteins were examined by Western blotting, immunofluorescence, Masson's trichrome and Sirius red staining. In addition, normal hepatocyte cell MIHA and hepatic stellate cell LX-2 were used as in vitro cell models to experimentally validate the effects of TCS by immunological, proteomic and metabolomic technologies.
We established a relatively short term TCS exposure murine model and found the TCS mainly accumulated in the liver. The scRNA-seq performed on the livers of the TCS-treated and control group profiled the gene expressions of > 76,000 cells belonging to 13 major cell types. Among these types, hepatocytes and hepatic stellate cells (HSCs) were significantly increased in TCS-treated group. We found that TCS promoted fibrosis-associated proliferation of hepatocytes, in which Gata2 and Mef2c are the key driving TFs. Our data also suggested that TCS induced the proliferation and activation of HSCs, which was experimentally verified in both liver tissue and cell model. In addition, other changes including the dysfunction and capillarization of endothelial cells, an increase of fibrotic characteristics in B plasma cells, and M2 phenotype-skewing of macrophage cells, were also deduced from the scRNA-seq analysis, and these changes are likely to contribute to the progression of liver fibrosis. Lastly, the key differential ligand-receptor pairs involved in cellular communications were identified and we confirmed the role of GAS6_AXL interaction-mediated cellular communication in promoting liver fibrosis.
TCS modulates the cellular activities and fates of several specific cell types (including hepatocytes, HSCs, endothelial cells, B cells, Kupffer cells and liver capsular macrophages) in the liver, and regulates the ligand-receptor interactions between these cells, thereby promoting the proliferation and activation of HSCs, leading to liver fibrosis. Overall, we provide the first comprehensive single-cell atlas of mouse livers in response to TCS and delineate the key cellular and molecular processes involved in TCS-induced hepatotoxicity and fibrosis.
Abstract
Background
Realizing imaging detection of water and nitrogen content in different regions of plant leaves in-site and real-time can provide an efficient new technology for determining crop ...drought resistance and nutrient regulation mechanisms, or for use in precision agriculture. Near-infrared imaging is the preferred technology for in-situ real-time detection owing to its non-destructive nature; moreover, it provides rich information. However, the use of hyperspectral imaging technology is limited as it is difficult to use it in field because of its high weight and power.
Results
We developed a smart imaging device using a near-infrared camera and an interference filter; it has a low weight, requires low power, and has a multi-wavelength resolution. The characteristic wavelengths of the filter that realize leaf moisture measurement are 1150 and 1400 nm, respectively, the characteristic wavelength of the filter that realizes nitrogen measurement is 1500 nm, and all filter bandwidths are 25 nm. The prediction result of the average leaf water content model obtained with the device was R
2
= 0.930, RMSE = 1.030%; the prediction result of the average nitrogen content model was R
2
= 0.750, RMSE = 0.263 g.
Conclusions
Using the average water and nitrogen content model, an image of distribution of water and nitrogen in different areas of corn leaf was obtained, and its distribution characteristics were consistent with the actual leaf conditions. The experimental materials used in this research were fresh leaves in the field, and the test was completed indoors. Further verification of applying the device and model to the field is underway.
•Granitoids in the Jiamusi Massif were emplaced at 530–484Ma.•The granitoid magams were derived from the partial melting of a dominantly Paleo-Mesoproterozoic “old” source.•The early Paleozoic ...granitoids formed in a post-collisional extensional setting.
This paper reports geochronological, whole-rock geochemical and zircon Hf-isotopic data for the early Paleozoic granitic rocks in the Jiamusi Massif in the eastern segment of the Central Asian Orogenic Belt (CAOB), in order to investigate their precise geochronological framework, petrogenesis, sources and tectonic setting. LA-ICP-MS zircon U–Pb age data indicate that the syenogranite, monzogranite and granodiorite were emplaced during the period of 530–484Ma. Geochemically, these granitoids have high SiO2 (64.66–79.17%) and K2O (3.08–7.33%), low MgO (0.14–2.63%) and CaO (0.37–3.87%), with A/CNK and δEu values of 0.89–1.10 and 0.16–1.77, respectively. These rocks are characterized by enrichment in Rb and Nd, and depletion in Nb, Ta, P and Ti. In addition, in-situ Hf isotopic analyses of zircons from the granitic rocks reveal that they have εHf (t)=−5.8 to +2.3, with two-stage Hf model ages (TDM2) varying from 1.3Ga to 2.4Ga, indicating that they probably originated from the partial melting of a dominantly “old” Paleo-Mesoproterozoic crustal source. Additionally, these granites have variable major and trace element concentrations. Magmatic zircons from these rocks record consistent homogeneous U–Pb ages but have heterogeneous εHf (t) values, reflecting that they resulted from fractional crystallization and crustal assimilation. Based on these geochemical data combined with regional geological investigations, we propose that the early Paleozoic granitic magmatism in the study area occurred in a post-collisional extensional setting, which was probably related to the collapse of a thickened crust.
There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-L1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular ...carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval CI, 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio HR, 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 16.1-27.3 vs. 15.7 months 13.0-20.2; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.
Glioblastoma (GBM) is the most aggressive brain tumor, with high mortality. Timosaponin AIII (TIA), a steroidal saponin isolated from the medicinal plant
Bge., has been shown to possess anticancer ...properties in various cancer types. However, the effect of TIA on GBM is unknown. In this study, we reveal that TIA not only inhibited U87MG in vitro cell growth but also in vivo tumor development. Moreover, we found that the cause of TIA-induced cell growth suppression was apoptosis. When seeking to uncover antitumor mechanisms of TIA, we found that TIA diminished the expression of cGMP-specific phosphodiesterase 5(PDE5) while elevating the levels of guanylate cyclases (sGCβ), cellular cGMP, and phosphorylation of VASP
. Following the knockdown of PDE5, PDE5 inhibitor tadalafil and cGMP analog 8-Bro-cGMP both inhibited cell growth and inactivated β-catenin; we reason that TIA elicited an antitumor effect by suppressing PDE5, leading to the activation of the cGMP signaling pathway, which, in turn, impeded β-catenin expression. As β-catenin is key for cell growth and survival in GBM, this study suggests that TIA elicits its anti-tumorigenic effect by interfering with β-catenin function through the activation of a PDE5/cGMP functional axis.
Authentication and adulteration detection of closely related herbal medicines is a thorny issue in the quality control and market standardization of traditional Chinese medicine. Taking Fritillariae ...Bulbus (FB) as a case study, we herein proposed a three-step strategy that integrates mass spectrometry-based metabolomics and multivariate statistical analysis to identify specific markers, thereby accurately identifying FBs and determining the adulteration level. First, an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based untargeted metabolomics method was employed to profile steroid alkaloids in five sorts of FB and screen potential differential markers. Then, the reliability of the screened markers was further verified by the distribution in different FB groups acquired from ultra-high performance liquid chromatography triple quadrupole mass spectrometry-based pseudotargeted metabolomics analysis. As a result, a total of 16 compounds were screened out to be the specific markers, which were successfully applied to distinguish five FBs by using discriminant analysis model. Besides, partial least squares regression models based on specific markers allowed accurate prediction of three sets of adulterated FBs. All the models afforded good linearity and good predictive ability with regression coefficient of prediction (R2p) > 0.9 and root mean square error of prediction (RMSEP) < 0.1. The reliable results of discriminant and quantitative analysis revealed that this proposed strategy could be potentially used to identify specific markers, which contributes to rapid chemical discrimination and adulteration detection of herbal medicines with close genetic relationship.
Display omitted
•Untargeted and pseudotargted metabolomics were integrated for marker discovery.•Five Fritillariae Bulbus were successfully distinguished based on specific markers.•Adulterated Fritillariae Bulbus was quantified by PLSR with good predictive accuracy.
Unisexual taxa are commonly considered short-lived as the absence of meiotic recombination is supposed to accumulate deleterious mutations and hinder the creation of genetic diversity. However, the ...gynogenetic gibel carp (Carassius gibelio) with high genetic diversity and wide ecological distribution has outlived its predicted extinction time of a strict unisexual reproduction population. Unlike other unisexual vertebrates, males associated with supernumerary microchromosomes have been observed in gibel carp, which provides a unique system to explore the rationales underlying male occurrence in unisexual lineage and evolution of unisexual reproduction. Here, we identified a massively expanded satellite DNA cluster on microchromosomes of hexaploid gibel carp via comparing with the ancestral tetraploid crucian carp (Carassius auratus). Based on the satellite cluster, we developed a method for single chromosomal fluorescence microdissection and isolated three male-specific microchromosomes in a male metaphase cell. Genomic anatomy revealed that these male-specific microchromosomes contained homologous sequences of autosomes and abundant repetitive elements. Significantly, several potential male-specific genes with transcriptional activity were identified, among which four and five genes displayed male-specific and male-biased expression in gonads, respectively, during the developmental period of sex determination. Therefore, the male-specific microchromosomes resembling common features of sex chromosomes may be the main driving force for male occurrence in gynogenetic gibel carp, which sheds new light on the evolution of unisexual reproduction.
Several quorum sensing systems occurring in
Bacillus subtilis
, e.g. Rap-Phr systems, were reported to interact with major regulatory proteins, such as ComA, DegU, and Spo0A, in order to regulate ...competence, sporulation, and synthesis of secondary metabolites. In this study, we characterized a novel Rap-Phr system, RapA4-PhrA4, in
Bacillus velezensis
NAU-B3. We found that the
rapA4
and
phrA4
genes were co-transcribed in NAU-B3. When
rapA4
was expressed in the heterologous host
Bacillus subtilis
OKB105, surfactin production and sporulation were severely inhibited. However, when the
phrA4
was co-expressed, the RapA4 activity was inhibited. The transcription of the surfactin synthetase
srfA
gene and sporulation-related genes were also regulated by the RapA4-PhrA4 system. In vitro results obtained from electrophoretic mobility shift assay (EMSA) proved that RapA4 inhibits ComA binding to the promoter of the
srfA
operon, and the PhrA4 pentapeptide acts as anti-activator of RapA4. We also found that the F24 residue plays a key role in RapA4 function. This study indicated that the novel RapA4-PhrA4 system regulates the surfactin synthesis and sporulation via interaction with ComA, thereby supporting the bacterium to compete and to survive in a hostile environment.
Key points
•Bacillus velezensis NAU-B3 has a novel Rap-Phr quorum sensing system, which does not occur in model strains Bacillus subtilis 168 and B. velezensis FZB42.
•RapA4-PhrA4 regulates surfactin production and sporulation.
•RapA4-PhrA4 interacts with the ComA protein from ComP/ComA two-component system.
Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for ...both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.
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