Our study provides the first experimental investigation of the internal flows of ventilated partial cavitation (VPC) formed by air injection behind a backward-facing step. The experiments are ...conducted using flow visualization and planar particle image velocimetry with fog particles for two different cavity regimes of VPC, i.e., open cavity (OC) and two-branch cavity (TBC), under various ranges of free stream velocity (
U
) and ventilation rates (
Q
). Our experiments reveal similar flow patterns for both OC and TBC, including forward flow region near the air–water interface, reverse flow region, near-cavitator vortex, and internal flow circulation vortex. However, OC internal flow exhibits highly unsteady internal flow features, while TBC internal flow shows laminar-like flow patterns with a Kelvin–Helmholtz instability developed at the interface between forward and reverse flow regions within the cavity. Internal flow patterns and the unsteadiness of OC resemble those of turbulent flow separation past a backward-facing step (BFS flow), suggesting a strong coupling of internal flow and turbulent external recirculation region for OC. Likewise, internal flow patterns of TBC resemble those of laminar BFS flow, with the presence of unsteadiness due to the strong velocity gradient across the forward–reverse flow interface. The variation in the internal flow upon changing
U
or
Q
is further employed to explain the cavity regime transition and the corresponding change of cavity geometry. Our study suggests that the ventilation control can potentially stabilize the cavity in the TBC regime by delaying its internal flow regime transition from laminar-like to highly unsteady.
Graphic abstract
Clear cell renal cell carcinoma (ccRCC) still remains a higher mortality rate in worldwide. Obtaining promising biomakers is very crucial for improving the diagnosis and prognosis of ccRCC patients. ...Herein, we firstly identified eight potentially prognostic miRNAs (hsa-miR-144-5p, hsa-miR-223-3p, hsa-miR-365b-3p, hsa-miR-3613-5p, hsa-miR-9-5p, hsa-miR-183-5p, hsa-miR-335-3p, hsa-miR-1269a). Secondly, we found that a signature containing these eight miRNAs showed obviously superior to a single miRNA in the prognostic effect and credibility for predicting the survival of ccRCC patients. Thirdly, we discovered that twenty-two transcription factors (TFs) interact with these eight miRNAs, and a signature combining nine TFs (
,
,
,
,
,
,
,
, and
) could promote the prognosis of ccRCC patients. Finally, we further identified eleven genes (hsa-miR-365b-3p, hsa-miR-223-3p, hsa-miR-1269a, hsa-miR-144-5p, hsa-miR-183-5p, hsa-miR-335-3p,
,
,
,
,
) that could combine as a signature to improve the prognosis effect of ccRCC patients, which distinctly outperformed the eight-miRNA signature and the nine-TF signature. Overall, we identified several new prognosis factors for ccRCC, and revealed a potential mechanism that TFs and miRNAs interplay cooperatively or oppositely regulate a certain number of tumor suppressors, driver genes, and oncogenes to facilitate the survival of ccRCC patients.
Background: Breast cancer (BC) is the most common malignancy in women with high heterogeneity. The heterogeneity of cancer cells from different BC subtypes has not been thoroughly characterized and ...there is still no valid biomarker for predicting the prognosis of BC patients in clinical practice. Methods: Cancer cells were identified by calculating single cell copy number variation using the inferCNV algorithm. SCENIC was utilized to infer gene regulatory networks. CellPhoneDB software was used to analyze the intercellular communications in different cell types. Survival analysis, univariate Cox, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox analysis were used to construct subtype specific prognostic models. Results: Triple-negative breast cancer (TNBC) has a higher proportion of cancer cells than subtypes of HER2+ BC and luminal BC, and the specifically upregulated genes of the TNBC subtype are associated with antioxidant and chemical stress resistance. Key transcription factors (TFs) of tumor cells for three subtypes varied, and most of the TF-target genes are specifically upregulated in corresponding BC subtypes. The intercellular communications mediated by different receptor–ligand pairs lead to an inflammatory response with different degrees in the three BC subtypes. We establish a prognostic model containing 10 genes (risk genes: ATP6AP1, RNF139, BASP1, ESR1 and TSKU; protective genes: RPL31, PAK1, STARD10, TFPI2 and SIAH2) for luminal BC, seven genes (risk genes: ACTR6 and C2orf76; protective genes: DIO2, DCXR, NDUFA8, SULT1A2 and AQP3) for HER2+ BC, and seven genes (risk genes: HPGD, CDC42 and PGK1; protective genes: SMYD3, LMO4, FABP7 and PRKRA) for TNBC. Three prognostic models can distinguish high-risk patients from low-risk patients and accurately predict patient prognosis. Conclusions: Comparative analysis of the three BC subtypes based on cancer cell heterogeneity in this study will be of great clinical significance for the diagnosis, prognosis and targeted therapy for BC patients.
There have been reports of long coronavirus disease (long COVID) and breakthrough infections (BTIs); however, the mechanisms and pathological features of long COVID after Omicron BTIs remain unclear. ...Assessing long-term effects of COVID-19 and immune recovery after Omicron BTIs is crucial for understanding the disease and managing new-generation vaccines. Here, we followed up mild BA.2 BTI convalescents for six-month with routine blood tests, proteomic analysis and single-cell RNA sequencing (scRNA-seq). We found that major organs exhibited ephemeral dysfunction and recovered to normal in approximately six-month after BA.2 BTI. We also observed durable and potent levels of neutralizing antibodies against major circulating sub-variants, indicating that hybrid humoral immunity stays active. However, platelets may take longer to recover based on proteomic analyses, which also shows coagulation disorder and an imbalance between anti-pathogen immunity and metabolism six-month after BA.2 BTI. The immunity-metabolism imbalance was then confirmed with retrospective analysis of abnormal levels of hormones, low blood glucose level and coagulation profile. The long-term malfunctional coagulation and imbalance in the material metabolism and immunity may contribute to the development of long COVID and act as useful indicator for assessing recovery and the long-term impacts after Omicron sub-variant BTIs.
Anthocyanins are natural colorants are synthesized in a branch of the flavonoid pathway. Dihydroflavonol-4reductase (DFR) catalyzes dihydroflavonoids into anthocyanins biosynthesis, which is a key ...regulatory enzyme of anthocyanin biosynthesis in plants. Hosta ventricosa is an ornamental plant with elegant flowers and rich colorful leaves. How the function of HvDFR contributes to the anthocyanins biosynthesis is still unknown. In this study, the DFR homolog was identified from H. ventricosa and sequence analysis showed that HvDFR possessed the conserved NADPH binding and catalytic domains. A phylogenetic analysis showed that HvDFR was close to the clade formed with MaDFR and HoDFR in Asparagaceae. Gene expression analysis revealed that HvDFR was constitutive expressed in all tissues and expressed highly in flower as well as was positively correlated with anthocyanin content. In addition, the subcellular location of HvDFR showed that is in the nucleus and cell membrane. Overexpression of HvDFR in transgenic tobacco lines enhanced the anthocyanins accumulation along with the key genes upregulated, such as F3H, F3ʹH, ANS, and UFGT. Our results indicated a functional activity of the HvDFR, which provide an insight into the regulation of anthocyanins content in H. ventricosa.
Background
Breast cancer shows a highly complex tumor microenvironment by containing various cell types. Identifying prognostic cell populations in the tumor microenvironment will improve the ...mechanistical understanding of breast cancer and facilitate the development of new breast cancer therapies by targeting the tumor microenvironment. The development of single‐cell sequencing reveals various cell types, states, and lineages within the context of heterogenous breast tumors, but identifying phenotype‐associated subpopulations is challenging.
Results
Here, we applied Scissor (single‐cell identification of subpopulations with bulk Sample phenotype correlation) to integrate single cell and bulk data of breast cancer, and found that MHC‐deficient tumor cells, FABP5+ macrophages, and COL1A1+ cancer‐associated fibroblasts (CAFs) were detrimental to patient survival, while T cells and dendritic cells were the main protective cells. MHC‐deficient tumor cells show strong downregulation of MHC expression for immune evasion by downregulating interferon and JAK‐STATs signaling. FABP5+ macrophages show low antigen‐presenting activity via associating with lipid metabolism. Our data suggest that COL1A1+ CAFs may block T‐cell immune infiltration through cell interaction in breast tumor microenvironment.
Conclusion
Taken together, our study reveals survival‐associated subpopulations in breast tumor microenvironment. Importantly, subpopulations related to immune evasion of breast cancer is uncovered.
Integrating single cell data and bulk data to identify prognostic cells and their molecular characteristics related to survival of breast cancer.
Anthocyanins are natural colorants are synthesized in a branch of the flavonoid pathway. chalcone isomerase gene
HvCHI
catalyzes the conversion of chalcones to flavanones which is a key regulatory ...enzyme of anthocyanin biosynthesis in plants.
Hosta ventricosa
is an ornamental plant with elegant flowers and rich colorful leaves. How the function of
HvCHI
contributes to the anthocyanins biosynthesis is still unknown. In this study, the
CHI
homolog was identified from
H. ventricosa
and sequence analysis showed that HvCHI possessed the conserved substrate binding and catalytic domains. A phylogenetic analysis showed HvCHI had a strong sister relationship with
Dracaena cambodiana
CHI. Gene expression analysis revealed that
HvCHI
was constitutive expressed in all tissues and expressed highly in flower as well as was positively correlated with anthocyanin content. In addition, the subcellular location of HvCHI showed that is in cytoplasm. Overexpression of
HvCHI
in transgenic tobacco lines enhanced the anthocyanins accumulation along with the key genes upregulated, such as
NtF3H
,
NtF3′H
,
NtF3′5′H
,
NtDFR
,
NtUFGT
, and
NtANS
. Our results indicated a functional activity of the
HvCHI
, which provide an insight into the regulation of anthocyanins content in
H. ventricosa.
Currently, adult cochlear hair cells (HCs) lack the capacity to regenerate, particularly the hearing damage caused by the HC damage are hard to recover. Remarkably, Lgr5+ inner ear progenitor cells ...can be activated to proliferate and regenerate hair cells (HCs) in response to injury, but the epigenetic regulatory roles in HC regeneration from Lgr5+ progenitor cells remain unresolved to date. We here investigate the possible roles of H3K4me3 modification in Lgr5+ progenitor cell proliferation and HC regeneration, and identify these differentially expressed genes associated with different binding regions between untreated Lgr5+ progenitor cells (ULPs) and neomycin-treated Lgr5+ progenitor cells (NLPs). Especially, H3K4me3 modification drives 12 genes involved in regulating proliferation and HC regeneration. Interestingly, we find that transcription factors Zeb1, Fev and Prdm5 are enriched in distinct peaks, implying their probable important roles in modulating neomycin-induced Lgr5+ progenitor cell proliferation and HC regeneration. Overall, our study demonstrates the underlying roles of H3k4me3 modification in Lgr5+ progenitor cell proliferation and HCs regeneration, and provides candidate H3K4me3 modification targets and regulators for subsequent studies.
PDF
