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Abstract Emerging evidence shows that FAT atypical cadherin 1 (FAT1) mutations occur in lymphoma and are associated with poorer overall survival. Considering that diffuse large B cell lymphoma (DLBCL) is the category of lymphoma with the highest incidence rate, this study aims to explore the role of FAT1 in DLBCL. The findings demonstrate that FAT1 inhibits the proliferation of DLBCL cell lines by downregulating the expression of YAP1 rather than by altering its cellular localization. Mechanistic analysis via meRIP-qPCR/luciferase reporter assays showed that FAT1 increases the m6A modification of YAP1 mRNA 3′UTR and the subsequent binding of heterogeneous nuclear ribonucleoprotein D (HNRNPD) to the m6A modified YAP1 mRNA, thus decreasing the stability of YAP1 mRNA. Furthermore, FAT1 increases YAP1 mRNA 3′UTR m6A modification by decreasing the activity of the TGFβ-Smad2/3 pathway and the subsequent expression of ALKBH5, which is regulated at the transcriptional level by Smad2/3. Collectively, these results reveal that FAT1 inhibits the proliferation of DLBCL cells by increasing the m6A modification of the YAP1 mRNA 3’UTR via the TGFβ-Smad2/3-ALKBH5 pathway. The findings of this study therefore indicate that FAT1 exerts anti-tumor effects in DLBCL and may represent a novel target in the treatment of this form of lymphoma.

Abstract Background In patients with hypertrophic cardiomyopathy (HCM), ischemic myocardial fibrosis assessed by late gadolinium enhancement (I-LGE) using cardiovascular magnetic resonance (CMR) have been reported. However, the clinical significance of I-LGE has not been completely understood. We aim to evaluate the I-LGE differ phenotypically from HCM without LGE or nonischemic myocardial fibrosis assessed by late gadolinium enhancement (NI-LGE) in the left ventricle (LV). Methods The patients with HCM whom was underwent CMR were enrolled, using cine cardiac magnetic resonance to evaluate LV function and LGE to detect the myocardial fibrosis. Three groups were assorted: 1) HCM without LGE; 2) HCM with LGE involved the subendocardial layer was defined as I-LGE; 3) HCM with LGE not involved the subendocardial layer was defined as NI-LGE. Results We enrolled 122 patients with HCM in the present study. LGE was detected in 58 of 122 (48%) patients with HCM, and 22 (18%) of patients reported I-LGE. HCM with I-LGE had increased higher left ventricular mass index (LVMI) (P

The resonant excitation of Bloch Surface Waves (BSWs) in dielectric one-dimensional photonic crystals is becoming a realistic photonic solution for surface integration in many domains, from spectroscopy to local field management. Bringing BSWs to ultrafast and nonlinear regimes requires a deep knowledge of the effects that the photonic crystal dispersion and the resonant surface wave excitation have on the ultrashort laser pulses. We report on the experimental evidence of spectral and temporal modifications of the radiation leaving a planar one-dimensional photonic crystal after coupling to BSWs. In such a resonant condition, a characteristic long temporal tail is observed in the outgoing pulses. Observations are performed by employing both frequency-resolved optical gating and field cross-correlation techniques.

Mitogen-activated protein kinase kinase 1 (MAPK kinase 1, MEK1) is a key kinase in the mitogen-activated protein kinase (MAPK) signaling pathway. MEK1 mutations have been reported to lead to abnormal activation that is closely related to the malignant growth and spread of various tumors, making it an important target for cancer treatment. Targeting MEK1, four small-molecular drugs have been approved by the FDA, including Trametinib, Cobimetinib, Binimetinib, and Selumetinib. Recently, a study showed that modification with dehydroalanine (Dha) can also lead to abnormal activation of MEK1, which has the potential to promote tumor development. In this study, we used molecular dynamics simulations and metadynamics to explore the mechanism of abnormal activation of MEK1 caused by the Dha modification and predicted the inhibitory effects of four FDA-approved MEK1 inhibitors on the Dha-modified MEK1. The results showed that the mechanism of abnormal activation of MEK1 caused by the Dha modification is due to the movement of the active segment, which opens the active pocket and exposes the catalytic site, leading to sustained abnormal activation of MEK1. Among four FDA-approved inhibitors, only Selumetinib clearly blocks the active site by changing the secondary structure of the active segment from α-helix to disordered loop. Our study will help to explain the mechanism of abnormal activation of MEK1 caused by the Dha modification and provide clues for the development of corresponding inhibitors.

ObjectiveRice blast is considered as the most destructive disease that threatens global rice production and causes severe economic losses worldwide. The detection of rice blast in an early manner plays an important role in resistance breeding and plant protection. At present, most studies on rice blast detection have been devoted to its symptomatic stage, while none of previous studies have used solar-induced chlorophyll fluorescence (SIF) to monitor rice leaf blast (RLB) at early stages. This research was conducted to investigate the early identification of RLB infected leaves based on solar-induced chlorophyll fluorescence at different leaf positions.MethodsGreenhouse experiments and field trials were conducted separately in Nanjing and Nantong in July and August, 2021, in order to record SIF data of the top 1th to 4th leaves of rice plants at jointing and heading stages with an Analytical Spectral Devices (ASD) spectrometer coupled with a FluoWat leaf clip and a halogen lamp. At the same time, the disease severity levels of the measured samples were manually collected according to the GB/T 15790-2009 standard. After the continuous wavelet transform (CWT) of SIF spectra, separability assessment and feature selection were applied to SIF spectra. Wavelet features sensitive to RLB were extracted, and the sensitive features and their identification accuracy of infected leaves for different leaf positions were compared. Finally, RLB identification models were constructed based on linear discriminant analysis (LDA).Results and DiscussionThe results showed that the upward and downward SIF in the far-red region of infected leaves at each leaf position were significantly higher than those of healthy leaves. This may be due to the infection of the fungal pathogen Magnaporthe oryzae, which may have destroyed the chloroplast structure, and ultimately inhibited the primary reaction of photosynthesis. In addition, both the upward and downward SIF in the red region and the far-red region increased with the decrease of leaf position. The sensitive wavelet features varied by leaf position, while most of them were distributed in the steep slope of the SIF spectrum and wavelet scales 3, 4 and 5. The sensitive features of the top 1th leaf were mainly located at 665-680 nm, 755-790 nm and 815-830 nm. For the top 2th leaf, the sensitive features were mainly found at 665-680 nm and 815-830 nm. For the top 3th one, most of the sensitive features lay at 690 nm, 755-790 nm and 815-830 nm, and the sensitive bands around 690 nm were observed. The sensitive features of the top 4th leaf were primarily located at 665-680 nm, 725 nm and 815-830 nm, and the sensitive bands around 725 nm were observed. The wavelet features of the common sensitive region (665-680 nm), not only had physiological significance, but also coincided with the chlorophyll absorption peak that allowed for reasonable spectral interpretation. There were differences in the accuracy of RLB identification models at different leaf positions. Based on the upward and downward SIF, the overall accuracies of the top 1th leaf were separately 70% and 71%, which was higher than other leaf positions. As a result, the top 1th leaf was an ideal indicator leaf to diagnose RLB in the field. The classification accuracy of SIF wavelet features were higher than the original SIF bands. Based on CWT and feature selection, the overall accuracy of the upward and downward optimal features of the top 1th to 4th leaves reached 70.13%、63.70%、64.63%、64.53% and 70.90%、63.12%、62.00%、64.02%, respectively. All of them were higher than the canopy monitoring feature F760, whose overall accuracy was 69.79%, 61.31%, 54.41%, 61.33% and 69.99%, 58.79%, 54.62%, 60.92%, respectively. This may be caused by the differences in physiological states of the top four leaves. In addition to RLB infection, the SIF data of some top 3th and top 4th leaves may also be affected by leaf senescence, while the SIF data of top 1th leaf, the latest unfolding leaf of rice plants was less affected by other physical and chemical parameters. This may explain why the top 1th leaf responded to RLB earlier than other leaves. The results also showed that the common sensitive features of the four leaf positions were also concentrated on the steep slope of the SIF spectrum, with better classification performance around 675 and 815 nm. The classification accuracy of the optimal common features, ↑WF832,3 and ↓WF809,3, reached 69.45%, 62.19%, 60.35%, 63.00% and 69.98%, 62.78%, 60.51%, 61.30% for the top 1th to top 4th leaf positions, respectively. The optimal common features, ↑WF832,3 and ↓WF809,3, were both located in wavelet scale 3 and 800-840nm, which may be related to the destruction of the cell structure in response to Magnaporthe oryzae infection.ConclusionsIn this study, the SIF spectral response to RLB was revealed, and the identification models of the top 1th leaf were found to be most precise among the top four leaves. In addition, the common wavelet features sensitive to RLB, ↑WF832,3 and ↓WF809,3, were extracted with the identification accuracy of 70%. The results proved the potential of CWT and SIF for RLB detection, which can provide important reference and technical support for the early, rapid and non-destructive diagnosis of RLB in the field.

Objective: Preferred biomass hydrolysis for preparation of arabinose and its kinetic analysis during the hydrolysis process. Methods: Single factor experiment and response surface methodology were used to optimize the conditions for the preparation of arabinose from gum Arabic by dilute acid hydrolysis, and the kinetics of the hydrolysis process was studied. Results: The optimum hydrolysis conditions were as follows: reaction time 237 min, sulfuric acid concentration 0.16 mol/L, reaction temperature 91 ℃. Three parallel experiments were carried out under these conditions. The average concentration of L-arabinose in the hydrolysate was 35.45 g/L. The kinetic parameters of arabinose formation and degradation were obtained by Saeman model fitting. The hydrolysis of Arabic gum is an internal diffusion controlled reaction process. Conclusion: The hydrolysis process of gum Arabic is a continuous pseudo homogeneous first-order reaction process, and the Saeman model can better describe the hydrolysis process of gum Arabic to arabinose.