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Tao Ren

Publications and source records attributed to Tao Ren.

13 recordsLinked to original sources
PubMed2025

OmicsTweezer: A distribution-independent cell deconvolution model for multi-omics Data.

Cell deconvolution estimates cell type proportions from bulk omics data, enabling insights into tissue microenvironments and disease. However, practical applications are often hindered by batch effects between bulk data and referenced single-cell data, a challenge that is frequently overlooked. To address this discrepancy, we developed OmicsTweezer, a distribution-independent cell deconvolution model. By integrating optimal transport with deep learning, OmicsTweezer aligns simulated and real data in a shared latent space, effectively mitigating data shifts and inter-omics distribution differences. OmicsTweezer is versatile, capable of deconvolving bulk RNA-seq, bulk proteomics, and spatial transcriptomics. Extensive evaluations on simulated and real-world datasets demonstrate its robustness and accuracy. Furthermore, applications in prostate and colon cancer showcase OmicsTweezer's ability to identify biologically meaningful cell types. As a unified deconvolution framework for multi-omics data, OmicsTweezer offers an efficient and powerful tool for studying disease microenvironments.

Humans↗
PubMed2006

Flagellin-deficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity.

Macrophages from C57BL/6J (B6) mice restrict growth of the intracellular bacterial pathogen Legionella pneumophila. Restriction of bacterial growth requires caspase-1 and the leucine-rich repeat-containing protein Naip5 (Birc1e). We identified mutants of L. pneumophila that evade macrophage innate immunity. All mutants were deficient in expression of flagellin, the primary flagellar subunit, and failed to induce caspase-1-mediated macrophage death. Interestingly, a previously isolated flagellar mutant (fliI) that expresses, but does not assemble, flagellin did not replicate in macrophages, and induced macrophage death. Thus, flagellin itself, not flagella or motility, is required to initiate macrophage innate immunity. Immunity to Legionella did not require MyD88, an essential adaptor for toll-like receptor 5 (TLR5) signaling. Moreover, flagellin of Legionella and Salmonella induced cytotoxicity when delivered to the macrophage cytosol using Escherichia coli as a heterologous host. It thus appears that macrophages sense cytosolic flagellin via a TLR5-independent pathway that leads to rapid caspase-1-dependent cell death and provides defense against intracellular bacterial pathogens.

Animals↗
PubMed2006

[Therapeutic effects and mechanisms of CpG oligodeoxynucleotides in mice infected with Mycobacterium tuberculosis].

OBJECTIVE: To investigate the protective effects and mechanisms of CpG oligodeoxynucleotides (CpG ODN) in mice infected with Mycobacterium tuberculosis. METHODS: Ninety-six female BALB/c mice were randomized into 4 groups, namely CpG ODN treatment (A group), control ODN treatment (B group), infection control (C group) and healthy control (D group) (n = 24 each). A group and B group were treated once with CpG ODN or control ODN (30 microg/mouse) intraperitoneally 2 weeks before infection with Mycobacterium tuberculosis. 1 x 10(6) bacili in a volume of 300 microl saline was injected into the tail vein of mice from A group, B group and C group. Twelve mice from each group were sacrificed at 3 weeks postinfection. Pathologic changes in lung tissues were observed. The expression of Toll-like receptor 9 (TLR9) mRNA and cytokine mRNA was detected by RT-PCR. The numbers of viable bacteria in lung and spleen were counted. The rest 12 mice from each group were monitored for 60 days to observe the mortality. RESULTS: CpG ODN was shown to increase the survival time of mice infected with Mycobacterium tuberculosis. The body weights of mice from A group [(20.37 +/- 1.12) g] were higher than those of B group [(17.50 +/- 0.62) g] and C group [(17.15 +/- 0.97) g, P < 0.01]. The lung weights of mice from A group [(0.25 +/- 0.02) g] were similar to those of B group [(0.27 +/- 0.34) g, P > 0.05], but less than those of C group [(0.28 +/- 0.26) g, P < 0.01]. The spleens of mice from A group [(0.63 +/- 0.37) g] were larger than those of B group [(0.39 +/- 0.05) g] and C group [(0.38 +/- 0.02) g, P < 0.01]. The inflammation in lung tissue of mice from A group was less than that of B group and C group. There was no mycobacterial outgrowth in lungs and spleens of mice from A group. The expression of TLR9 mRNA in lungs and spleens of mice from A group (0.61 +/- 0.29 and 0.72 +/- 0.48) was similar to that in B group (0.58 +/- 0.35 and 0.64 +/- 0.28) and C group (0.60 +/- 0.32 and 0.65 +/- 0.31, P > 0.05), but higher than that in D group (0.11 +/- 0.08 and 0.26 +/- 0.22, P < 0.01). CpG ODN did not affect the expression of TLR9 mRNA. The expression of IFN-gamma mRNA in lungs and spleens of mice from A group (0.44 +/- 0.07 and 0.76 +/- 0.09) was higher than that in B group (0.19 +/- 0.05 and 0.22 +/- 0.05) and C group (0.16 +/- 0.04 and 0.18 +/- 0.08, P < 0.01). The expression of IL-6 mRNA in lungs and spleens of mice from A group (1.56 +/- 0.29 and 8.21 +/- 0.82) was higher than that in B group (0.86 +/- 0.55 and 0.16 +/- 0.09) and C group (0.78 +/- 0.21 and 0.06 +/- 0.04, P < 0.01). The expression of IL-4 mRNA in lungs and spleens of mice from A group (0.18 +/- 0.05 and 0.06 +/- 0.02) was lower than that in B group (0.31 +/- 0.06 and 1.22 +/- 0.01) and C group (0.35 +/- 0.04 and 1.31 +/- 0.31, P < 0.01). The expression of IL-10 mRNA in spleens of mice from A group (0.05 +/- 0.02) was lower than that in B group (0.57 +/- 0.09) and C group (0.65 +/- 0.15, P < 0.01). CONCLUSION: CpG ODN could increase the immunity of mice against tuberculosis through up-regulation of Th1 immunity and down-regulation of Th2 immunity.

Animals↗
PubMed2006

[The effects of CpG-oligodeoxynucleotides on airway remodeling in chronic asthmatic mice].

OBJECTIVE: To investigate if CpG-oligodeoxynucleotides (CpG-ODN) intervention has inhibitory effects on the development of airway remodeling in an ovalbumin (OVA)-sensitized mouse model of chronic asthma. METHODS: Forty female C57BL/6 mice were randomly divided into four groups (n = 10): (1) Group A (chronic asthma model): mice were sensitized by intraperitoneal injection of OVA (10 microg) precipitated with aluminium hydroxide (100 microg) on days 1 and 14. From day 21, the mice were challenged by nebulized 2.5% OVA solution (30 min/d, three times a week for 8 weeks). (2) Group B (CpG-ODN intervention group): mice were sensitized and challenged as above, and were given 60 microg CpG-ODN by intraperitoneal injection for once every two weeks. (3) Group C (GpG-ODN control): Mice were given GpC-ODN instead of CpG motifs, other treatments same as Group B. (4) Group D (saline control): mice were sensitized and challenged by saline. All mice were killed 24 h after the final OVA challenge. Blood was obtained for eosinophil counts and measurement of serum IgE by enzyme-linked immunoabsorbent assay (ELISA). Bronchoalveolar lavage fluid (BALF) was collected for total and differential counts. The concentration of interleukin-13 (IL-13) and transforming growth factor-beta1 (TGF-beta(1)) in BALF was measured by ELISA. The left lung was isolated for pathological examination. Lung sections were stained with hematoxylin and eosin (HE), and Masson's trichrome. Other sections were prepared for immunohistochemistry using monoclonal antibodies against alpha-smooth muscle actin (alpha-SMA) and TGF-beta(1). RESULTS: The eosinophil count [(89 +/- 10) x 10(4)/ml], serum IgE [(279 +/- 53) ng/ml], BALF eosinophils [(6.30 +/- 1.30) x 10(5)/ml] and the concentrations of BALF IL-13 [(4 015 +/- 361) pg/ml] and TGF-beta(1) [(356 +/- 64) pg/ml] in the OVA-sensitized mice (Group A) showed significant difference as compared with those in the NS control group (Group D, t values are 24.0, 15.7, 14.7, 18.4, 12.0 and 18.9 respectively, all P < 0.01). In Group A, the percentages of positive staining area in Masson's trichrome, alpha-SMA staining and TGF-beta(1) staining were (29.7 +/- 4.2)%, (45 +/- 7)% and (34 +/- 4)% respectively. These percentages were significantly different from those in the NS control group (Group D, t values are 18.0, 15.6 and 17.9 respectively, all P < 0.01). In mice treated with CpG-ODN (Group B), the percentages of positive staining area in Masson's trichrome, alpha-SMA staining and TGF-beta(1) staining were (13.8 +/- 3.2)%, (24.7 +/- 3.1)%, (18 +/- 4)% respectively, which were significantly different from those in Group A (t values are 9.5, 8.9 and 9.8 respectively, all P < 0.05). CONCLUSIONS: This study demonstrated that CpG-ODN could prevent Th2 responses, eosinophilic inflammation and the development of airway remodeling. Its inhibitory effect on airway remodeling might, in part, be due to inhibition of the expression of cytokines such as TGF-beta(1) and IL-13.

Airway Remodeling↗
PubMed2005

The nuclear localization of the Arabidopsis transcription factor TIP is blocked by its interaction with the coat protein of Turnip crinkle virus.

We have previously reported that TIP, an Arabidopsis protein, interacts with the coat protein (CP) of Turnip crinkle virus (TCV) in yeast cells and that this interaction correlated with the resistance response in the TCV-resistant Arabidopsis ecotype Dijon-17. TIP was also able to activate transcription of reporter genes in yeast cells, suggesting that it is likely a transcription factor. We have now verified the physical interaction between TIP and TCV CP in vitro and showed that CP mutants unable to interact with TIP in yeast cells bind TIP with much lower affinity in vitro. Secondly, we have performed gel shift experiments demonstrating that TIP does not bind to DNA in a sequence-specific manner. The subcellular localization of TIP was also investigated by transiently expressing green fluorescence protein (GFP)-tagged TIP in Nicotiana benthamiana plant cells, which showed that GFP-tagged TIP localizes primarily to nuclei. Significantly, co-expression of TCVCP and GFP-TIP prevented the nuclear localization of TIP. Together, these results suggest that TIP might be a transcription factor involved in regulating the defense response of Arabidopsis to TCV and that its normal role is compromised by interaction with the invading viral CP.

Active Transport, Cell Nucleus↗
PubMed2004

RNA silencing-suppressor function of Turnip crinkle virus coat protein cannot be attributed to its interaction with the Arabidopsis protein TIP.

The interaction of the coat protein (CP) of Turnip crinkle virus (TCV) with a host protein, TCV-interacting protein (TIP), from Arabidopsis thaliana has been reported previously. This interaction correlates with the ability of TCV CP to elicit the resistance response that is mediated by the resistance gene HRT in Arabidopsis ecotype Di-17. It has also been established that TCV CP is a suppressor of RNA silencing, a process by which the host plant targets viral RNA for degradation. These results have led to the speculation that TIP might be a component of the RNA-silencing pathway and that TCV CP suppresses RNA silencing through its interaction with TIP. In the current report, a number of TCV CP mutants have been investigated for their ability to suppress RNA silencing. These mutants include single amino acid substitution mutants that are known to have lost their ability to interact with TIP, as well as deletion mutants of TCV CP that are of different sizes and from different regions of the protein. Results showed that each of the single amino acid substitution mutants tested retained high levels of RNA silencing-suppressor activity. In addition, a mutant containing a 5 aa deletion in the region that is known to be critical for TIP interaction retained the ability to suppress RNA silencing significantly. Larger deletions in all regions of TCV CP abolished silencing-suppressor activity. It can be concluded from these results that the RNA silencing-suppressor activity of TCV CP cannot be attributed to its ability to interact directly with TIP.

Arabidopsis↗
PubMed2004

Antibodies to SARS coronavirus in civets.

Using three different assays, we examined 103 serum samples collected from different civet farms and a market in China in June 2003 and January 2004. While civets on farms were largely free from SARS-CoV infection, approximately 80% of the animals from one animal market in Guangzhou contained significant levels of antibody to SARS-CoV, which suggests no widespread infection among civets resident on farms, and the infection of civets in the market might be associated with trading activities under the conditions of overcrowding and mixing of various animal species.

Animals↗
PubMed2004

Mechanism of acetaminophen-induced apoptosis in cultured cells: roles of caspase-3, DNA fragmentation factor, and the Ca2+ and Mg2+ endonuclease DNAS1L3.

We have recently shown that acetaminophen induces many of the apoptotic traits in hepatoma cells and lymphocytes (Boulares et al. (2002d). In an effort to further investigate the mechanism by which non-metabolized acetaminophen induces apoptosis, we have now examined the roles of caspase-3, the DNA fragmentation factor, and the poly(ADP-ribose) polymerase-1-regulated Ca2+ and Mg2+-dependent endonuclease DNAS1L3 in the induction of such death process. This was achieved with the use of MCF-7 cells, a caspase-3-deficient breast adenocarcinoma cell line, thymocytes isolated from DFF45 (the inhibitory and chaperone subunit of the DNA fragmentation factor subunit, DFF40) deficient mice, and HeLa cells, a DNAS1L3-deficient cervical carcinoma cell line. MCF-7 exhibited a marked resistance to acetaminophen treatment. Ectopic expression of human caspase-3 significantly potentiated the cytotoxic effect of acetaminophen and promoted the release of cytochrome c into the cytosol of treated cells suggesting a direct role for caspase-3 in acetaminophen-induced apoptosis. Expression and cleavage of DFF45 were required but not sufficient for acetaminophen-induced internucleosomal DNA fragmentation. DFF45 gene knockout rendered thymocytes resistant against acetaminophen-induced generation of both large and internucleosomal DNA fragments. The treatment of HeLa cells with acetaminophen resulted in internuclesomal DNA fragmentation only after transfection of these cells with a plasmid encoding the DNAS1L3 gene suggesting that this endonuclease is required for acetaminophen-induced internucleosomal DNA fragmentation. DNAS1L3 expression potentiated the cytotoxic effect of acetaminophen in HeLa cells suggesting an active role in the death process induced by this drug. Altogether, these results demonstrate the specific roles of caspase-3, DNA fragmentation factor, and DNAS1L3 in the process of acetaminophen-induced apoptosis in cultured cells.

Acetaminophen↗
PubMed2003

[The cross-sectional study of awareness and practice of SARS epidemic in community residents in Beijing].

OBJECTIVE: To investigate the awareness and practice of SARS in community residents in Beijing. METHODS: A cross-sectional study was conducted in different-level communities of SARS epidemic strength in Beijing. Typical samples were selected and 480 residents were surveyed. RESULTS: 92% of the residents focused on SARS epidemic in Beijing and 72.5% didn't worry that they would be attacked by SARS. The sources of stress included fatal outcomes, lack of efficient treatment, rapid spreading and high risk of medical workers. 86.8% felt the media often over-reported. 50% were afraid of going to the clinics. 86% thought that measures taken by the government were active and efficient. Meanwhile, 60% could follow the government recommendation to prevent SARS. CONCLUSION: Most of the residents believe SARS have influenced on regular life, stability of society, development of economy and international communication.

Adolescent↗
PubMed2003

The coat protein of turnip crinkle virus suppresses posttranscriptional gene silencing at an early initiation step.

Posttranscriptional gene silencing (PTGS), or RNA silencing, is a sequence-specific RNA degradation process that targets foreign RNA, including viral and transposon RNA for destruction. Several RNA plant viruses have been shown to encode suppressors of PTGS in order to survive this host defense. We report here that the coat protein (CP) of Turnip crinkle virus (TCV) strongly suppresses PTGS. The Agrobacterium infiltration system was used to demonstrate that TCV CP suppressed the local PTGS as strongly as several previously reported virus-coded suppressors and that the action of TCV CP eliminated the small interfering RNAs associated with PTGS. We have also shown that the TCV CP must be present at the time of silencing initiation to be an effective suppressor. TCV CP was able to suppress PTGS induced by sense, antisense, and double-stranded RNAs, and it prevented systemic silencing. These data suggest that TCV CP functions to suppress RNA silencing at an early initiation step, likely by interfering the function of the Dicer-like RNase in plants.

Brassica napus↗
PubMed2003

[An analysis on the cost of hypertensive outpatient in the community hospital in Shanghai].

OBJECTIVE: To study the cost of the hypertensive outpatients. METHODS: The study randomly selected 460 insured patients with hypertension and investigated their cost on each case in the out-patient department through 2002, based on the electronic system of medical insurance. RESULTS: As a whole, the distribution of hypertensive outpatient expenditure takes on the positively skewed, with the median of 1 567.9 Yuan RMB. With the increase of age, the average expenses in each age group increased accordingly. In the study, the average number of outpatient attendances per patient was 19.5, the average expenses per visit was 115.4 Yuan RMB. In age groups 40 - 49 and 50 - 59, expenses of outpatient in male and female groups are obviously different in 2002 (Wilcoxon W(40 - 49) = 36, P(40 - 49) = 0.037; Wilcoxon W(50 - 59) = 374, P(50 - 59) = 0.023), as well as the number of out-patients (Wilcoxon W(40 - 49) = 52.5, P(40 - 49) = 0.007; Wilcoxon W(50 - 59) = 379, P(50 - 59) = 0.028). When considering the factors of gender and age at one time, the outpatient expenditures in the male group were significantly different between the different age groups (chi(2) = 22.3, P < 0.001), as well as the number of outpatients (chi(2) = 25.4, P < 0.001). In addition, the expenditure of drugs, which took a large proportion of the total expenditure of hypertensive outpatients (about 83.6 percent), was divided into three parts according to the degree of correlation with hypertension: direct expenses related to the with disease, the indirect expenses and the irrespective. The proportions of each part were 19.9 percent, 32.3 percent and 47.8 percent respectively. CONCLUSION: When economic evaluation of community prevention is carried out, the cost and cost-benefit analysis based on the analysis of outpatient expenditure and the proportion of expenses on hypertension should be taken into account. Additionally, to provide appropriate mode of medicare, to impact the behaviors and expenditure of patients, and to provide low-cost but good effective drug are also essential and important factors.

Adult↗
PubMed2002

[Modulation of allergic airway inflammation by immunostimulatory DNA sequences in conjunction with an allergen in a murine model of asthma].

OBJECTIVE: To compare the suppressive effects of immunostimulatory sequences (ISS-DNA) alone or ISS-DNA in conjunction with ovalbumin (OVA) on airway inflammation in a mouse model of asthma. METHODS: Thirty six female BALB/c mice were divided into 4 groups: group ISS (A), group ISS + OVA (B), group OVA (C) and group normal saline (D). Mice in groups A, B and C were sensitized and challenged with OVA. Group A and group B were subdivided into subgroup A(1) and B(1) (injected intraperitoneally with ISS DNA 100 micro g or ISS DNA 100 micro g and OVA 10 micro g once) and subgroup A(2) and B(2) (injected intraperitoneally with ISS DNA or ISS DNA and OVA twice). Blood samples were obtained every week for six weeks. OVA-specific IgE was measured by ELISA. Bronchoalveolar lavage fluid (BALF), lung tissues and spleen cells were collected. BAL total cell numbers and differentials were counted. Interferon gamma (IFN-gamma) produced by OVA-stimulated spleen cells was determined by ELISA. RESULTS: Eosinophil count in group A(1) [(2.39 +/- 0.81) x 10(4)/ml], group A(2) [(2.62 +/- 0.77) x 10(4)/ml], group B(1) [(1.80 +/- 0.12) x 10(4)/ml], and group B(2) [(1.84 +/- 0.67) x 10(4)/ml] were significantly lower than those in group C [(12.43 +/- 2.13) x 10(4)/ml], P < 0.05. The levels of IFN-gamma in group A(1) [(510 +/- 102) pg/ml], group A(2) [(492 +/- 98) pg/ml], group B(1) [(532 +/- 120) pg/ml], and group B(2) [(469 +/- 132) pg/ml] were significantly higher than those in group C [(194 +/- 80) pg/ml], P < 0.05. The serum level of IgE in group B was significantly lower than that in group C in four weeks, but that in group A was not significantly different from that in group C. A second dose of ISS-DNA did not show additional effect as compared to the signal dose treatment. CONCLUSIONS: ISS-DNA inhibited allergic airway inflammation in a murine model of asthma. ISS-DNA and OVA combination was more effective than ISS-DNA alone.

Adjuvants, Immunologic↗