To gain mechanistic insights into the functions and developmental dynamics of tumor-infiltrated immune cells, especially B-lymphocytes, here we combine single-cell RNA-sequencing and antigen receptor ...lineage analysis to characterize a large number of triple-negative breast cancer infiltrated immune cells and report a comprehensive atlas of tumor-infiltrated B-lymphocytes. The single-cell transcriptional profiles reveal significant heterogeneity in tumor-infiltrated B-cell subgroups. The single-cell antigen receptor analyses demonstrate that compared with those in peripheral blood, tumor-infiltrated B-cells have more mature and memory B-cell characteristics, higher clonality, more class switching recombination and somatic hypermutations. Combined analyses suggest local differentiation of infiltrated memory B-cells within breast tumors. The B-cell signatures based on the single-cell RNA-sequencing results are significantly associated with improved survival in breast tumor patients. Functional analyses of tumor-infiltrated B-cell populations suggest that mechanistically, B-cell subgroups may contribute to immunosurveillance through various pathways. Further dissection of tumor-infiltrated B-cell populations will provide valuable clues for tumor immunotherapy.
We aimed to analyze the action of berberine on the neuropathic pain and neuroglia activation in experimental diabetes mellitus (DM) model. Diabetes in mice was induced by intraperitoneal injection of ...streptozotocin (STZ) followed by the administration of berberine. Mechanical allodynia and thermal hyperalgesia and activations of microglia and astrocytes were evaluated. The levels of pro-inflammatory cytokines and protein expressions of inflammatory proteins were assessed by enzyme-linked immunosorbent assay (ELISA) and western blot, respectively. Our results revealed the anti-nociceptive effects of berberine in DM mice, supported by the improved mechanical threshold and thermal latency. In addition, berberine suppressed the activations of microglia and astrocytes in the spinal cords of diabetic mice. Berberine inhibited the expression of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and interleukin-1β (IL-1β), along with inflammatory proteins including iNOS and COX-2. Berberine suppressed neuropathic pain in STZ-induced diabetic mice, and this effect is related to the reduction on the neuroglia activation and inflammation associated with DM.
A chemical investigation of the arils of
led to the isolation of seven abietane-type diterpenoids (compounds
-
) including three previously undescribed compounds, one unreported natural product, and ...three known analogs. The structures of these compounds were determined by means of spectroscopy, single-crystal X-ray diffraction, and ECD spectra. An antibacterial activity assay showed that compounds
and
had significant inhibitory effects on methicillin-resistant
, with MIC values of 100 μM. Moreover, compounds
,
,
, and
exhibited anti-neuroinflammatory activity in LPS-stimulated BV-2 microglia cells, with the IC
values ranging from 38.4 to 67.9 μM.
Diabetic peripheral neuropathy (DPN) is one of the most important complications in diabetes mellitus (DM), which has been reported to be modulated by long non-coding RNAs (lncRNAs). The purpose of ...the current study is to explore the regulatory mechanism of lncRNA HCG18 on DPN in vitro. The expression of lncRNA HCG18, miR-146a, TRAF6, CD11c, and iNOS was detected by qRT-PCR. Through Enzyme-linked immunosorbent assay, the levels of inflammatory factors (TNF-α, IL-1β, and IL-6) were determined. M1 macrophage polarization was measured by flow cytometry analysis. The interactions between miR-146a and HCG18/TRAF6 were predicted by Starbase/Targetscan software and verified by the dual luciferase reporter assay. Western blot assay was performed to determine the protein expression of TRAF6. LncRNA HCG18 was highly expressed in DPN model and HG-induced macrophages. The levels of inflammatory factors (TNF-α, IL-1β, and IL-6) were elevated in DPN model. The expression of M1 markers (CD11c and iNOS) was visibly up-regulated in DPN model and was positively correlated with HCG18 expression. LncRNA HCG18 facilitated M1 macrophage polarization. In addition, miR-146a was identified as a target of lncRNA HCG18. Overexpression of miR-146a reversed the promoting effect of HCG18 on M1 macrophage polarization. Simultaneously, TRAF6 was a target gene of miR-146a TRAF6 expression was positively modulated by HCG18 and was negatively modulated by miR-146a. Down-regulation of TRAF6 reversed the promoting effect of HCG18 on M1 macrophage polarization. LncRNA HCG18 promotes M1 macrophage polarization via regulating the miR-146a/TRAF6 axis, facilitating the progression of DPN. This study provides a possible therapeutic strategy for DPN.
•We developed the longest Chinese pine tree-ring chronology available in the ECLP.•The ECLP showed a clear and continuous drying trend since 1960s.•The recent drought is not unprecedented over the ...past 500 years in the ECLP.•The North Atlantic SST tripolar pattern play a role in modulating droughts in the ECLP.
Northern China has experienced dramatic drying since the 1960s CE. However, the scarcity of long-term observations hampers the evaluation of recent drought variations from a long-term perspective. Here, we present a tree-ring-width chronology of Chinese pine (Pinus tabuliformis Carr.) from the eastern edge of the Chinese Loess Plateau (ECLP), which is the longest tree-ring chronology on the ECLP (1535–2018 CE). This chronology was used to reconstruct the average April-June self-calibrated Palmer Drought Severity Index (scPDSI). The reconstruction explains 64.3% of the variations in the observed scPDSI during the calibration period (1954–2000 CE). The driest and wettest years over the full reconstruction were 1759 CE and 1649 CE, respectively. The two most prolonged drought intervals occurred in 1892–1943 CE and 1737–1775 CE, while the two most prolonged pluvial intervals occurred in 1950–1992 CE and 1645–1682 CE. The reconstruction captures the recent drying since the 1960s. However, we found that the recent notable drying is not unprecedented over the last half-millennium, as more dramatic drought fluctuations occurred around the 1650s-1690s. The spatial correlation with sea surface temperature (SST) indicates that the drought variations on the ECLP might be modulated by the North Atlantic SST tripolar pattern. This study provides a reference for long-term drought evaluation, which may have implications for drought prediction and adaptation on the ECLP.
Purpose
The composition of endophytic communities has been shown to depend on grape genotypes and viticultural managements in leaves, stems, and berries of grape, but there have been relatively few ...reports exploring fungal endophytes associated with wild grape and foliar age.
Methods
The regions of internally transcribed spacer (ITS) were sequenced using the Illumina HiSeq to determine the diversity of fungal endophytes associated with European grape (
Vitis vinifera
cv. Red Globe) and Chinese wild grape (
Vitis amurensis
cv. Shuangyou) in young and mature leaves.
Results
A total of 3 phyla, 23 classes, 51 orders, 97 families, and 150 fungal genera were identified. Young leaves have significantly higher diversity and richness than that in mature leaves in both cultivars. Endophytic fungal diversity was greater in wild grapevines (119 genera) than in cultivated grapevines (81 genera) in both young and mature leaves. Endophytic fungal community structure was also significantly different between young leaves and mature leaves as well as in both cultivars based on statistical tests of ANOSIM and MRPP.
Conclusions
Our results suggest that endophytic fungal communities were strongly affected by foliar age and domestication, which are crucial factors in establishing symbiotic associations with a selective enrichment for specific endophytes.
In eukaryotes, DNA double-strand breaks (DSBs), one of the most harmful types of DNA damage, are repaired by homologous repair (HR) and nonhomologous end-joining (NHEJ). Surprisingly, in cells ...deficient for core classic NHEJ factors such as DNA ligase IV (Lig4), substantial end-joining activities have been observed in various situations, suggesting the existence of alternative end-joining (A-EJ) activities. Several putative A-EJ factors have been proposed, although results are mostly controversial. By using a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, we generated mouse CH12F3 cell lines in which, in addition to Lig4, either Lig1 or nuclear Lig3, representing the cells containing a single DNA ligase (Lig3 or Lig1, respectively) in their nucleus, was completely ablated. Surprisingly, we found that both Lig1- and Lig3-containing complexes could efficiently catalyze A-EJ for class switching recombination (CSR) in the IgH locus and chromosomal deletions between DSBs generated by CRISPR/Cas9 in cis-chromosomes. However, only deletion of nuclear Lig3, but not Lig1, could significantly reduce the interchromosomal translocations in Lig4−/− cells, suggesting the unique role of Lig3 in catalyzing chromosome translocation. Additional sequence analysis of chromosome translocation junction microhomology revealed the specificity of different ligase-containing complexes. The data suggested the existence of multiple DNA ligase-containing complexes in A-EJ.
Ongoing climatic warming is obvious and has significantly affected the ecosystem of the Qinling Mountains, the highest mountain region in mainland of Eastern China. Putting the progressive warming ...into a long-term perspective is challenging in the region due to the shortness of instrumental records. Here, we present an annual (December–November) minimum temperature reconstruction for the western Qinling Mountains from 1675 CE. The study area has experienced a continuous warming since the 1860s, and the temperature after the 1980s is unprecedented over the past three centuries. The similar variations between our reconstruction and temperature reconstructions for Asia and Northern Hemisphere indicate the close linkage between the thermal variation in the western Qinling Mountains and large-scale climate systems. Atlantic Multidecadal Oscillation (AMO) may be the primary driver influencing regional climate during the past three centuries. In addition, solar activity, strong volcanic eruption and greenhouse gas forcing have potential effects on temperature variations in the western Qinling Mountains. This study provides a long-term context for observed warming, which may have implications for warming prediction and adaptation in the western Qinling Mountains.
•Tree rings provide an annual Tmin record of western Qinling Mountains since 1675 CE.•The warming after the 1980s is unprecedented over the past three centuries.•AMO may be the key factor for regional long-term temperature variations.
is an ascomycetous fungus that causes grape anthracnose, a potentially devastating disease worldwide. Here, we report a 28.29 Mb high-quality genome sequence of
YL-1 that encodes 8,057 predicted ...protein-coding genes and represents the first sequenced genome assembly of
. This study adds to the current genomic resources for the genus
and paves the way for research on comparative genomic studies,
-grape interactions, and improvement of management strategies.
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