In mammals, CD4 is found to be expressed on T cells and innate immune cells, however, teleost cells bearing CD4 have not been well identified and characterized. In this study, we identified two ...different CD4-1+ cell subsets in grass carp (Ctenopharyngodon idella): CD4-1+ lymphocytes (Lym) and CD4-1+ myeloid cells (Mye), both of which had the highest proportions in the head kidney. The mRNA expression analysis showed that CD4-1, CD4-2, TCRβ, CD3γ/δ, and LCK1 are highly expressed in CD4-1+ Lym and also expressed in CD4-1+ Mye. Furthermore, we found that CD4-1+ Lym have a Lym morphology and highly express T-cell cytokines, suggesting that they are CD4+ T cells equivalent to mammalian Th cells. On the other hand, CD4-1+ Mye were found to have a morphology of macrophage and highly express macrophage marker gene MCSFR, indicating that they are macrophages. In addition, functional analysis revealed that CD4-1+ Mye possess phagocytic ability and great antigen-processing ability. Taken together, our study sheds further light on the composition and function of CD4+ cells in teleost fish.
•CD4-1+ lymphocytes and CD4-1+ myeloid cells were identified in grass carp.•CD4-1+ lymphocytes highly expressed T-cell-related genes and Th-cell cytokines.•CD4-1+ myeloid cells were found to highly express macrophage-related genes.•CD4-1+ myeloid cells exhibited phagocytic and antigen-processing abilities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The modified Look-Locker inversion recovery (MOLLI) sequence is commonly used for myocardial T1 mapping. However, it acquires images with different inversion times, which causes difficulty in motion ...correction for respiratory-induced misregistration to a given target image.
Using a generative adversarial network (GAN) to produce virtual MOLLI images with consistent heart positions can reduce respiratory-induced misregistration of MOLLI datasets.
Retrospective.
1071 MOLLI datasets from 392 human participants.
Modified Look-Locker inversion recovery sequence at 3 T.
A GAN model with a single inversion time image as input was trained to generate virtual MOLLI target (VMT) images at different inversion times which were subsequently used in an image registration algorithm. Four VMT models were investigated and the best performing model compared with the standard vendor-provided motion correction (MOCO) technique.
The effectiveness of the motion correction technique was assessed using the fitting quality index (FQI), mutual information (MI), and Dice coefficients of motion-corrected images, plus subjective quality evaluation of T1 maps by three independent readers using Likert score. Wilcoxon signed-rank test with Bonferroni correction for multiple comparison. Significance levels were defined as P < 0.01 for highly significant differences and P < 0.05 for significant differences.
The best performing VMT model with iterative registration demonstrated significantly better performance (FQI 0.88 ± 0.03, MI 1.78 ± 0.20, Dice 0.84 ± 0.23, quality score 2.26 ± 0.95) compared to other approaches, including the vendor-provided MOCO method (FQI 0.86 ± 0.04, MI 1.69 ± 0.25, Dice 0.80 ± 0.27, quality score 2.16 ± 1.01).
Our GAN model generating VMT images improved motion correction, which may assist reliable T1 mapping in the presence of respiratory motion. Its robust performance, even with considerable respiratory-induced heart displacements, may be beneficial for patients with difficulties in breath-holding.
3 TECHNICAL EFFICACY: Stage 1.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Heteronemin, a marine sesterterpenoid-type natural product, possesses an antiproliferative effect in cancer cells. In addition, heteronemin has been shown to inhibit
expression. Our laboratory has ...demonstrated that the thyroid hormone deaminated analogue, tetrac, activates
and induces antiproliferation in colorectal cancer. However, such drug mechanisms are still to be studied in oral cancer cells.
We investigated the antiproliferative effects by Cell Counting Kit-8 and flow cytometry. The signal transduction pathway was measured by Western blotting analyses. Quantitative PCR was used to evaluate gene expression regulated by heteronemin, 3,3',5,5'-tetraiodothyroacetic acid (tetrac), or their combined treatment in oral cancer cells.
Heteronemin inhibited not only expression of proliferative genes and
(
) but also cell proliferation in both OEC-M1 and SCC-25 cells. Remarkably, heteronemin increased
expression in SCC-25 cells. Tetrac suppressed expression of
but not
expression in both cancer cell lines. Furthermore, the synergistic effect of tetrac and heteronemin inhibited ERK1/2 activation and heteronemin also blocked STAT3 signaling. Combined treatment increased p53 protein and p53 activation accumulation although heteronemin inhibited p53 expression in both cancer cell lines. The combined treatment induced antiproliferation synergistically more than a single agent.
Both heteronemin and tetrac inhibited ERK1/2 activation and increased p53 phosphorylation. They also inhibited
expression. Moreover, tetrac suppressed
expression combined with heteronemin to further enhance antiproliferation and anti-metastasis in oral cancer cells.
The efficacy of prenatal antiviral therapy (AVT) for preventing the vertical transmission of hepatitis B virus (HBV) is well demonstrated. However, data are limited regarding the safety of postpartum ...cessation of AVT, which may induce alanine aminotransferase (ALT) elevation. We aimed to investigate the necessity of prolonging maternal AVT after delivery. Chronic hepatitis B mothers at the immune‐tolerant phase with HBV DNA levels >6 log10 IU/mL were prospectively enrolled and received AVT during the third trimester until delivery. Patients were offered to discontinue AVT either at delivery or postpartum week (PPW) 6. In addition, mothers who deferred AVT during pregnancy served as the control group. All mothers were followed until PPW 52 for clinical and virological parameters of hepatitis flares. Among 118 mothers recruited, 91 received AVT with 53 (group A) and 24 (group B) discontinue their treatment at delivery and PPW 6, respectively. Twenty‐seven mothers who deferred AVT during pregnancy were followed as the control (group C). A total of 104 of 118 mothers who completed the study, 50% (52/104) had postpartum‐elevated ALT levels, which were mild and moderate except 6 of 104 (5.77%) of patients had levels ≥5 times the upper limit of normal; 70% (36/52) of the ALT flares occurred within 12 weeks after delivery. In subgroup analyses, the frequency of ALT elevation was similar among the groups A vs B vs C (50.9% 27/53 vs 58.3% 14/24 vs 40.7% 11/27, respectively; P = .447), as well as the mean peak ALT level (108.4/74.1/126.7 U/L in groups A/B/C, respectively; P = .291). Although postpartum ALT flares were common for mothers with or without AVT during pregnancy, most cases of ALT elevation were mild to moderate. Our study observed that extending AVT to PPW 6 did not affect maternal outcomes and ATV should be discontinued at birth. Close monitoring is warranted as severe flares rarely occurred.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The motile characteristics and mechanisms that drive the dissemination of diffuse large B-cell lymphoma (DLBCL) are elusive. Here, we show that DLBCL initiates dissemination through activating ...STAT3-mediated amoeboid migration. Mechanistically, STAT3 activates RHOH transcription, which competes with the RhoGDP dissociation inhibitor RhoGDIγ to activate RhoA. In addition, activated STAT3 regulates microtubule dynamics and releases ARHGEF2 to activate RhoA. Both the JAK inhibitor ruxolitinib and the microtubule stabilizer Taxol suppress DLBCL cell dissemination in vivo. A clinical DLBCL sample analysis shows that STAT3-driven amoeboid movement is particularly important for the transition from stage I to stage II. This study elucidates the mechanism of DLBCL dissemination and progression and highlights the potential of combating advanced DLBCL with a JAK/STAT inhibitor or microtubule stabilizer to reduce DLBCL motility; these findings may have a great impact on the development of patient-tailored treatments for DLBCL.
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•Fe3O4–PEI nanocomposites with large amount of NH2 groups were synthesized.•97% of harvesting efficiency for microalgal cells was obtained with the nanocomposites.•Magnetic separation ...provides a powerful tool for microalgae harvesting in practice.
Fe3O4 nanoparticles were functionally coated with polyethylenimine (PEI), which contained a high concentration of NH2 groups, for the efficient harvesting of microalgae. The functional magnetic nanocomposites were 12nm in diameter and 69.77emu/g of saturation magnetization. Using a nanocomposite dosage of 20mg/L for harvesting Chlorella ellipsoidea cells, a harvesting efficiency of 97% was achieved within 2min. Increasing the temperature resulted in an increase in harvesting efficiency. The adsorption isotherm data fit the Langmuir model, suggesting that the adsorption was monolayer. The adsorption capacity of the Fe3O4–PEI nanocomposites for the microalgal cells reached up to 93.46g-DCW/g-nanocomposites through electrostatic attraction and nanoscale interactions between the nanocomposites and the microalgal cells. The functional nanocomposites provide a base for efficient microalgae harvesting with clear advantages such as rapid execution, low energy consumption, and improves water-use in the algal harvesting process.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Traumatic brain injury (TBI), known as mechanical damage to the brain, impairs the normal function of the brain seriously. Its clinical symptoms manifest as behavioral impairment, cognitive decline, ...communication difficulties, etc. The pathophysiological mechanisms of TBI are complex and involve inflammatory response, oxidative stress, mitochondrial dysfunction, blood-brain barrier (BBB) disruption, and so on. Among them, oxidative stress, one of the important mechanisms, occurs at the beginning and accompanies the whole process of TBI. Most importantly, excessive oxidative stress causes BBB disruption and brings injury to lipids, proteins, and DNA, leading to the generation of lipid peroxidation, damage of nuclear and mitochondrial DNA, neuronal apoptosis, and neuroinflammatory response. Transcription factor NF-E2 related factor 2 (Nrf2), a basic leucine zipper protein, plays an important role in the regulation of antioxidant proteins, such as oxygenase-1(HO-1), NAD(P)H Quinone Dehydrogenase 1 (NQO1), and glutathione peroxidase (GPx), to protect against oxidative stress, neuroinflammation, and neuronal apoptosis. Recently, emerging evidence indicated the knockout (KO) of Nrf2 aggravates the pathology of TBI, while the treatment of Nrf2 activators inhibits neuronal apoptosis and neuroinflammatory responses via reducing oxidative damage. Phytochemicals from fruits, vegetables, grains, and other medical herbs have been demonstrated to activate the Nrf2 signaling pathway and exert neuroprotective effects in TBI. In this review, we emphasized the contributive role of oxidative stress in the pathology of TBI and the protective mechanism of the Nrf2-mediated oxidative stress response for the treatment of TBI. In addition, we summarized the research advances of phytochemicals, including polyphenols, terpenoids, natural pigments, and otherwise, in the activation of Nrf2 signaling and their potential therapies for TBI. Although there is still limited clinical application evidence for these natural Nrf2 activators, we believe that the combinational use of phytochemicals such as Nrf2 activators with gene and stem cell therapy will be a promising therapeutic strategy for TBI in the future.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Despite the well-established recognition of the health hazards posed by PM2.5-bound PAHs, a comprehensive understanding of their source-specific impact has been lacking. In this study, the health ...risks associated with PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) and source-specific contributions were investigated in the urban region of Taipei during both cold and warm seasons. The levels of PM2.5-bound PAHs and their potential health risks across different age groups of humans were also characterized. Diagnostic ratios and positive matrix factorization analysis were utilized to identify the sources of PM2.5-bound PAHs. Moreover, potential source contribution function (PSCF), concentration-weighted trajectory (CWT) and source regional apportionment (SRA) analyses were employed to determine the potential source regions. Results showed that the total PAHs (TPAHs) concentrations ranged from 0.08 to 2.37 ng m−3, with an average of 0.69 ± 0.53 ng m−3. Vehicular emissions emerged as the primary contributor to PM2.5-bound PAHs, constituting 39.8 % of the TPAHs concentration, followed by industrial emissions (37.6 %), biomass burning (13.8 %), and petroleum/oil volatilization (8.8 %). PSCF and CWT analyses revealed that industrial activities and shipping processes in northeast China, South China Sea, Yellow Sea, and East China Sea, contributed to the occurrence of PM2.5-bound PAHs in Taipei. SRA identified central China as the primary regional contributor of ambient TPAHs in the cold season and Taiwan in the warm season, respectively. Evaluations of incremental lifetime cancer risk demonstrated the highest risk for adults, followed by children, seniors, and adolescents. The assessments of lifetime lung cancer risk showed that vehicular and industrial emissions were the main contributors to cancer risk induced by PM2.5-bound PAHs. This research emphasizes the essential role of precisely identifying the origins of PM2.5-bound PAHs to enhance our comprehension of the related human health hazards, thus providing valuable insights into the mitigation strategies.
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•Source-specific contributions and health risk of PM2.5-bound PAHs were identified.•Long-range transport significantly contributed to PM2.5-bound PAHs.•Vehicular was the main contributor to LLCR induced by PM2.5-bound PAHs.•The assessment of ILCR revealed the highest risk for adults.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Patients with advanced biliary tract cancer (BTC) have a poor prognosis, and novel treatments are needed. Gemcitabine, the standard of care for BTC, induces DNA damage; however, the ability of cancer ...cells to repair DNA dampens its effects. To improve the efficacy of gemcitabine, we combined it with MK1775, a Wee1 inhibitor that prevents activation of the G2/M checkpoint. BTC cell lines were treated with gemcitabine only or in combination with MK1775 to determine the therapeutic potential of BTC. Gemcitabine inhibited the growth and induced the apoptosis of four BTC cell lines to a greater extent when added with MK1775 than when added alone. The effects of the combination treatment were observed in both p53 wild-type and p53 mutant cell lines and were unaffected by knockdown of wild-type p53. The combination treatment increased the percentage of apoptotic cells and decreased the percentage of cells synthesizing DNA, suggesting that it caused DNA-damaged cells to accumulate and possibly die in S phase. It did not induce apoptosis when cells were arrested in mitosis using nocodazole. In a xenograft mouse model, gemcitabine plus MK1775 (but not either alone) inhibited the growth of tumors generated from inoculated BTC cells. Our results show that MK1775 highly enhances gemcitabine cytotoxicity in BTC regardless of p53 status. We suggest that the combination treatment elicits a DNA damage response and consequent apoptosis. Our preclinical study provides a basis for future clinical trials of gemcitabine plus MK1775 in patients with BTC.
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●The enhanced antitumor activity of gemcitabine with MK1775 was observed both in vitro and in vivo.●Combination treatment increased apoptosis and decreased DNA synthesis by accumulating DNA damage and replication stress in the S phase.●Potentiation of Wee1 inhibition by MK1775 on gemcitabine in BTC cells was p53-independent.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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