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•The cavitation evolution around the baseline and biomimetic hydrofoils is studied by LES approach.•Far-field cavitation noise for both hydrofoils is compared by permeable FW-H ...method.•The noise reduction mechanism of wavy leading edge is revealed.
This paper investigates the noise reduction performance of biomimetic hydrofoils with wavy leading edge and the corresponding mechanisms. We employ Large Eddy Simulation (LES) approach and permeable Ffowcs Williams-Hawkings (PFW–H) method to predict cavitation noise around the baseline and biomimetic hydrofoils. The results show that the wavy leading edge can effectively reduce the high-frequency noise, but has little effect on the low-frequency noise. Further analyses and discussions deal with the noise reduction mechanisms. The main source for the low-frequency noise is the cavity volume acceleration, while the wavy leading edge has little effect on it. The high-frequency noise sources, related to the surface pressure fluctuations and the turbulence characteristics, are significantly suppressed by the wavy leading edge, thus decreasing the high-frequency noise intensity. Our investigation indicates that the wavy leading edge has great prospects for cavitation noise reduction technique.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
UFMylation is a ubiquitination-like modification that is related to endoplasmic reticulum stress and unfolded protein response. A recent study reported that Ufl1, a key enzyme of UFMylation, ...protects against heart failure, indicating that UFMylation may be associated with heart function regulation. In the present study, we initially constructed a Flag-6×His-tagged Ufm1ΔSC transgenic (Tg-Ufm1) mouse model that enables UFMylation studies in vivo. Tg-Ufm1 mice showed significant activation of UFMylation in hearts. By using this model, we identified 38 potential Ufm1-binding proteins in heart tissues through LC‒MS/MS methods. We found that these proteins were associated with mitochondria, metabolism and chaperone binding. By using transcriptomic screening, we identified Tnfaip2 as a novel UFMylation-associated gene. Overexpression of Ufm1 significantly upregulated the protein expression of Tnfaip2, whereas isoproterenol treatment decreased Tnfaip2 expression in Tg-Ufm1 mice. These data may provide novel clues for UFMylation in cardiac hypertrophy.
Quantitative detection of protein biomarkers is crucial to medical diagnosis. Fluorescent probes have been frequently used for protein detection, but they suffered from various weaknesses such as ...lack of versatility. In particular, most of the reported probes were not capable of simultaneous qualitative and quantitative detection for various proteins. In this paper, we developed novel nanoparticle array-based near-infrared (NIR) ratiometric probes for potent protein analysis, in which the specific protein was able to be distinguished and quantitated within a group of 11 common proteins. The activity of β-galactosidases (β-gal) was temporarily inhibited by the adsorption to magnetic nanoparticles and restored to certain content by replacement with detected proteins, leading to distinctive readout of the enzyme-activatable NIR probe (DCM-β-gal). The readout of the sensor array against 11 proteins, as verified by isothermal titration calorimetry, was processed and transformed into canonical factors with the help of linear discrimination analysis. Moreover, the ratiometric signals of DCM-β-gal were translated to quantitatively detect proteins within the concentration range of 0–100 μg/mL. Based on clear differentiation within both two-dimensional and three-dimensional plots, different proteins could be detected with 100% accuracy with their concentration simultaneously determined, which endowed the sensing system with great potential in clinical diagnosis.
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IJS, KILJ, NUK, PNG, UL, UM
We studied the single‐molecule conductance through an acid oxidant triggered phenothiazine (PTZ‐) based radical junction using the mechanically controllable break junction technique. The electrical ...conductance of the radical state was enhanced by up to 200 times compared to the neutral state, with high stability lasting for at least two months and high junction formation probability at room‐temperature. Theoretical studies revealed that the conductance increase is due to a significant decrease of the HOMO–LUMO gap and also the enhanced transmission close to the HOMO orbital when the radical forms. The large conductance enhancement induced by the formation of the stable PTZ radical molecule will lead to promising applications in single‐molecule electronics and spintronics.
Single‐molecule conductances of phenothiazine radicals have been measured using the mechanically controllable break junction technique. Triggered by an acid oxidant, the radical cation of phenothiazine enhances the charge‐transport property by up to 200 times with high stability and high junction formation probability at room temperature, which leads to promising applications in single‐molecule electronics and spintronics.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective To explore the role of G protein pathway suppressor 2(GPS2)in regulating proliferation, migration and invasion in hepatocellular carcinoma cell line MHCC-97H.Methods The expression of GPS2 ...in hepatocellular carcinoma (HCC) cells were detected using quantitative PCR or Western blot; GPS2 was either over-expressed or knocked down in HCC cells using over-expression vectors or short hairpin RNAs (shRNAs) for GPS2, respectively. Clone formation assay, scratch assay and Transwell assay were used to detect the effects of GPS2 on proliferation, migration and invasion of HCC cells. Results In HCC cells, over-expression of GPS2 was found to inhibit the proliferation, migration and invasion of HCC cells MHCC-97H, while knockdown of GPS2 up-regulated proliferation, migration and invasion of MHCC-97H(P＜0.05). The over-expression of GPS2 in MHCC-97H cells was found to inhibit the expression of cell proliferation, migration and invasion-related factors such as EGFR, MMP1, MMP3 and MMP9, while knockdown of GPS2 upr
Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disease, which is characterized with overactive immune response. It is well established that the imbalance between Tregs and Th17 cells ...plays a pivotal role in pathogenesis of UC. In this study, we investigated the impact of functional changes in Treg subsets on Treg/Th17 ratio and further explored their clinical significance in the activity of UC. Treg subsets were comprehensively analysed using flow cytometry and in vitro cultured in both active and remission UC patients, of which nine active UC patients were further followed up. The correlation analyses were performed to explore the potential associations between Treg subsets and clinical indicators, as well as the impact of serum cytokines, detected by ELISA, on IL‐17A secretion and CCR6 co‐expression of Treg subsets. In active UC patients, we found CD45RA‐FoxP3hiTregs were obviously decreased and inversely correlated with disease activity, while CD45RA+FoxP3loTregs were increased and positively correlated with disease activity. Meanwhile, IL‐17A secretion and CCR6 co‐expression levels in Tregs were significantly increased in active UC. Moreover, Tregs co‐expressing CCR6 possesses higher level of IL‐17A secretion. In nine followed up patients, we observed downregulated IL‐17A secreting and CCR6 co‐expression when achieving remission from active stage. In addition, IL‐17A+FoxP3+ and IL‐17A+FoxP3+CCR6+Tregs were positively correlated with serum IL‐21 and disease activity, respectively. These findings suggested that upregulated IL‐17A secretion and CCR6 co‐expression in Treg subsets may be related to the imbalance between Tregs and Th17 cells and associated with the disease activity in UC patients.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Breast cancer (BC) is associated with hereditary components, and some deleterious germline variants have been regarded as effective therapeutic targets. We conducted a clinic-based, observational ...study to better understand the distribution of deleterious germline variants and assess any clinicopathological predictors related to the variants among Chinese BC patients using a 32 cancer-related genes next-generation sequencing panel. Between November 2020 and February 2022, a total of 700 BC patients were recruited, and 13.1% (92/700) of them carried deleterious germline variants in 15 cancer-related genes, including 37 (37/700, 5.3%) in BRCA2, 29 (29/700, 4.1%) in BRCA1, 8 (8/700, 1.1%) in PALB2, 4 (4/700, 0.6%) in NBN, 3 (3/700, 0.4%) in MRE11A, 3 (3/700, 0.4%) in TP53 and 12 (12/700, 1.7%) in other genes. There were 28 novel variants detected: 5 in BRCA1, 14 in BRCA2, and 9 in non-BRCA1/2 genes. The variants in panel genes, HRR (homologous recombination repair)-related genes, and BRCA1/2 were significantly associated with the following clinicopathological factors: age at the initial diagnosis of BC, family history of any cancer, molecular subtype, Ki-67 index, and hereditary risk. In conclusion, we further expanded the spectrum of germline deleterious variants in Chinese BC patients, and the clinicopathological predictors of variants were identified to facilitate clinical genetic testing and counseling for appropriate individuals.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum, in which the abnormality of B cells is involved in both its pathogenesis and progression. Follicular ...helper T cells (TFH) play an important role in assisting the immune function of human B cells in germinal centers, and follicular regulatory T cells (TFR) have the function of inhibiting TFH and germinal center B cell responses. The significance of circulating TFH and TFR in ulcerative colitis (UC) remains unclear. We analyzed peripheral blood of active and stable remission UC patients and found that circulating TFR was significantly decreased while TFH was increased in active UC patients. As to TFH subsets, TFH2 was elevated while TFH17 was decreased in active UC, with IL-4/IL-17A secretion enhanced. Helios
and CD45RA
FoxP3
TFR cells were decreased while CD226
and CD45RA
FoxP3
TFR cells were increased in active UC patients. The levels of new memory B cells, plasmablasts and serum IgG were significantly increased in active UC patients, and were positively correlated with TFH and TFH2, and negatively correlated with TFR. Serum CRP and Mayo Clinic scores were positively correlated with TFH and TFH2 but negatively correlated with TFR. Serum IL-12 and IL-21 were up-regulated while IL-10 was down-regulated in active UC. To conclude, an imbalance of circulating TFH and TFR cells is associated with disease activity in UC patients. Our results suggest a new mechanism for TFH and TFR imbalance in the pathogenesis of UC, providing a new perspective for theoretical research and therapeutic strategies for UC.
Over the past two decades, dengue fever (DF) has emerged as a significant arboviral disease in Yunnan province, China, particularly in the China-Myanmar border area. Aedes aegypti, an invasive ...mosquito species, plays a crucial role in transmitting the dengue virus to the local population. Insecticide-based vector control has been the primary tool employed to combat DF, but the current susceptibility status of Ae. aegypti to commonly used insecticides is unknown. Assessment of Ae. aegypti resistance to pyrethroid insecticides and an understanding of the underlying mechanisms of this resistance in the China-Myanmar border region is of significant strategic importance for effectively controlling the DF epidemic in the area.
Aedes aegypti larvae collected from Ruili and Gengma counties in Yunnan Province were reared to adults in the laboratory and tested for susceptibility to three pyrethroid insecticides (3.20% permethrin, 0.08% lambda-cyhalothrin and 0.20% deltamethrin) by the standard WHO susceptibility bioassay. Genotyping of mutations in the knockdown gene (kdr), namely S989P, V1016G and F1534C, that are responsible for resistance to pyrethroid insecticides was performed using allele-specific PCR methods. A possible association between the observed resistant phenotype and mutations in the voltage-gated sodium channel gene (VGSC) was also studied.
Aedes aegypti mosquitoes collected from the two counties and reared in the laboratory were resistant to all of the pyrethroids tested, with the exception of Ae. aegypti from Gengma County, which showed sensitivity to 0.20% deltamethrin. The mortality rate of Ae. aegypti from Ruili county exposed to 3.20% permethrin did not differ significantly from that of Ae. aegypti from Gengma County (χ
= 0.311, P = 0.577). By contrast, the mortality rate of Ae. aegypti from Ruili County exposed to 0.08% lambda-cyhalothrin and 0.20% deltamethrin, respectively, was significantly different from that of Ae. aegypti from Gengma. There was no significant difference in the observed KDT
of Ae. aegypti from the two counties to various insecticides. Four mutation types and 12 genotypes were detected at three kdr mutation sites. Based on results from all tested Ae. aegypti, the V1016G mutation was the most prevalent kdr mutation (100% prevalence), followed by the S989P mutation (81.6%) and the F1534C mutation (78.9%). The constituent ratio of VGSC gene mutation types was significantly different in Ae. aegypti mosquitoes from Ruili and those Gengma. The triple mutant S989P + V1016G + F1534C was observed in 274 Ae. aegypti mosquitoes (60.8%), with the most common genotype being SP + GG + FC (31.4%). The prevalence of the F1534C mutation was significantly higher in resistant Ae. aegypti from Ruili (odds ratio OR 7.43; 95% confidence interval CI 1.71-32.29; P = 0.01) and Gengma (OR 9.29; 95% CI 3.38-25.50; P = 0.00) counties than in susceptible Ae. aegypti when exposed to 3.20% permethrin and 0.08% lambda-cyhalothrin, respectively. No significant association was observed in the triple mutation genotypes with the Ae. aegypti population exposed to 3.20% permethrin and 0.20% deltamethrin resistance (P > 0.05), except for Ae. aegypti from Gengma County when exposed to 0.08% lambda-cyhalothrin (OR 2.86; 95% CI 1.20-6.81; P = 0.02).
Aedes aegypti from Ruili and Gengma counties have developed resistance to various pyrethroid insecticides. The occurrence of multiple mutant sites in VGSC strongly correlated with the high levels of resistance to pyrethroids in the Ae. aegypti populations, highlighting the need for alternative strategies to manage the spread of resistance. A region-specific control strategy for dengue vectors needs to be implemented in the future based on the status of insecticide resistance and kdr mutations.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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