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Extracting rich feature representations is a key challenge in person re-identification (Re-ID) tasks. However, traditional Convolutional Neural Networks (CNN) based methods could ignore a part of information when processing local regions of person images, which leads to incomplete feature extraction. To this end, this paper proposes a person Re-ID method based on vision Transformer with hierarchical structure and window shifting. When extracting person image features, the hierarchical Transformer model is constructed by introducing the hierarchical construction method commonly used in CNN. Then, considering the importance of local information of person images for complete feature extraction, the self-attention calculation is performed by shifting within the window region. Finally, experiments on three standard datasets demonstrate the effectiveness and superiority of the proposed method.

Accumulating evidence indicated that activation of microglia and neuroinflammation reaction played a prominent role in Alzheimer's disease (AD). Inhibition of toll-like receptor 4 (TLR4) has been shown to be associated with immune responses and brain damage, but its effects on AD remain unclear. This study mainly aimed to investigate the protective effect of TAK-242 (TLR4 specific inhibitor) on the microglia polarization and neuroprotection in AD mouse model and the underlying mechanisms. We found that APP/PS1 transgenic AD mice exhibited a dramatic increase in TLR4 levels concomitant with a significantly higher expression of inflammatory microglia in contrast to C57BL/6 wild type mice. Furthermore, inhibiton of TLR4 by TAK-242 administration significantly improved neurological function, decreased the level of Bax and caused a significant reduction in the levels of M1-markers (iNOS and TNFα), while the expressions of M2-phenotype markers (Trem-2 and Arg-1) were increased both in vivo and in vitro. Furthermore, TAK-242 treatment enhanced BV2 microglial phagocytosis. Moreover, Aβ25-35 caused the upregulation of inflammatory cytokine production, MyD88, NF-kappaB-p65 and NLRP3, which could be ameliorated by NLRP3-siRNA or TAK-242, an inhibitor of TLR4. These findings indicated that TLR4 inhibition provided neuroprotection and promoted microglia switch from the inflammatory M1 phenotype to the protective M2 phenotype in AD. The mechanism may be related to modulation of the MyD88/NF-kappaB/NLRP3 signaling pathway.

Combined chemo/chemodynamic therapy is a promising strategy to achieve an improved anticancer effect. However, the hypoxic microenvironment and limited amount of H2O2 in most solid tumors severely restrict the efficacy of this treatment. Herein, the construction of a nanocatalytic medicine, CaO2@DOX@ZIF‐67, via a bottom‐up approach is described. CaO2@DOX@ZIF‐67 simultaneously supplies O2 and H2O2 to achieve improved chemo/chemodynamic therapy. In the weakly acidic environment within tumors, CaO2@DOX@ZIF‐67 is broken down to rapidly release the Fenton‐like catalyst Co2+ and the chemotherapy drug doxorubicin (DOX). The unprotected CaO2 reacts with H2O to generate both O2 and H2O2. The generated O2 relieves the hypoxia in the tumor and further improve the efficacy of DOX. Meanwhile, the generated H2O2 reacts with Co2+ ions to produce highly toxic •OH through a Fenton‐like reaction, resulting in improved chemodynamic therapy. The hypoxic microenvironment and limited amount of H2O2 in most solid tumors severely restrict the efficacy of chemotherapy and chemodynamic therapy, respectively. Herein, a nanocatalytic medicine, CaO2@DOX@ZIF‐67, is synthesized via a bottom‐up approach. By virtue of simultaneously producing O2 and H2O2 under acidic conditions, the fabricated nanocatalytic medicine can eliminate hypoxic tumors via enhanced chemo/chemodynamic therapy.

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies that has an unfavorable outcome and a high rate of relapse. Autophagy plays a vital role in the development of and therapeutic responses to leukemia. This study identifies a potential autophagy-related signature to monitor the prognoses of patients of AML. Transcriptomic profiles of AML patients (GSE37642) with the relevant clinical information were downloaded from Gene Expression Omnibus (GEO) as the training set while TCGA-AML and GSE12417 were used as validation cohorts. Univariate regression analyses and multivariate stepwise Cox regression analysis were respectively applied to identify the autophagy-related signature. The univariate Cox regression analysis identified 32 autophagy-related genes (ARGs) that were significantly associated with the overall survival (OS) of the patients, and were mainly rich in signaling pathways for autophagy, p53, AMPK, and TNF. A prognostic signature that comprised eight ARGs (BAG3, CALCOCO2, CAMKK2, CANX, DAPK1, P4HB, TSC2, and ULK1) and had good predictive capacity was established by LASSO–Cox stepwise regression analysis. High-risk patients were found to have significantly shorter OS than patients in low-risk group. The signature can be used as an independent prognostic predictor after adjusting for clinicopathological parameters, and was validated on two external AML sets. Differentially expressed genes analyzed in two groups were involved in inflammatory and immune signaling pathways. An analysis of tumor-infiltrating immune cells confirmed that high-risk patients had a strong immunosuppressive microenvironment. Potential druggable OS-related ARGs were then investigated through protein–drug interactions. This study provides a systematic analysis of ARGs and develops an OS-related prognostic predictor for AML patients. Further work is needed to verify its clinical utility and identify the underlying molecular mechanisms in AML.

Drug repositioning is gaining attention as a method for developing new drugs due to its low cost, short cycle time, and high success rate. One important approach is to explore new uses for already marketed drugs. In this study, we utilized the strategy of drug repositioning, focusing on the Dan-Lou tablet. We predicted the efficacy of Dan-Lou tablet against non-small cell lung cancer based on gene expression similarity and verified it by in vitro experiments. Next, we performed further analysis and validation using network pharmacology, molecular docking and molecular dynamics. Based on the results, it was concluded that Dan-Lou tablet mainly acted through nine compounds, Quercetin, Luteolin, Scoparone, Isorhamnetin, Eugenol, Genistein, Coumestrol, Hederagenin, Succinic Acid, and mainly targeted CCL2, FEN1, TPI1, RMI2 by six pathways. This discovery not only provides a new idea for the development of Dan-Lou tablet but also provides useful predictive information for clinical treatment. The method we adopted has great development prospects as a way to predict the efficacy of new drugs and their main mechanisms of action, and it has a positive impact on the research and development of new drugs using drug repositioning and the modernization of traditional Chinese medicine.

Homeostasis of the endoplasmic reticulum (ER) is essential for normal cellular functions. Disturbance of this homeostasis causes ER stress and activates the Unfolded Protein Response (UPR). The Ufm1 conjugation system is a novel Ubiquitin-like (Ubl) system whose physiological target(s) and biological functions remain largely undefined. Genetic study has demonstrated that the Ufm1-activating enzyme Uba5 is indispensible for erythroid differentiation in mice, highlighting the importance of this novel system in animal development. In this report we present the evidence for involvement of RCAD/Ufl1, a putative Ufm1-specific E3 ligase, and its binding partner C53/LZAP protein in ufmylation of endogenous Ufm1 targets. Moreover, we found that the Ufm1 system was transcriptionally up-regulated by disturbance of the ER homeostasis and inhibition of vesicle trafficking. Using luciferase reporter and ChIP assays, we dissected the Ufm1 promoter and found that Ufm1 was a potential target of Xbp-1, one of crucial transcription factors in UPR. We further examined the effect of Xbp-1 deficiency on the expression of the Ufm1 components. Interestingly, the expression of Ufm1, Uba5, RCAD/Ufl1 and C53/LZAP in wild-type mouse embryonic fibroblasts (MEFs) was significantly induced by inhibition of vesicle trafficking, but the induction was negated by Xbp-1 deficiency. Finally, we found that knockdown of the Ufm1 system in U2OS cells triggered UPR and amplification of the ER network. Taken together, our study provided critical insight into the regulatory mechanism of the Ufm1 system and established a direct link between this novel Ubl system and the ER network.

One of the problems of optical remote sensing of crop above-ground biomass (AGB) is that vegetation indices (VIs) often saturate from the middle to late growth stages. This study focuses on combining VIs acquired by a consumer-grade multiple-spectral UAV and machine learning regression techniques to (i) determine the optimal time window for AGB estimation of winter wheat and to (ii) determine the optimal combination of multi-spectral VIs and regression algorithms. UAV-based multi-spectral data and manually measured AGB of winter wheat, under five nitrogen rates, were obtained from the jointing stage until 25 days after flowering in the growing season 2020/2021. Forty-four multi-spectral VIs were used in the linear regression (LR), partial least squares regression (PLSR), and random forest (RF) models in this study. Results of LR models showed that the heading stage was the most suitable stage for AGB prediction, with R2 values varying from 0.48 to 0.93. Three PLSR models based on different datasets performed differently in estimating AGB in the training dataset (R2 = 0.74~0.92, RMSE = 0.95~2.87 t/ha, MAE = 0.75~2.18 t/ha, and RPD = 2.00~3.67) and validation dataset (R2 = 0.50~0.75, RMSE = 1.56~2.57 t/ha, MAE = 1.44~2.05 t/ha, RPD = 1.45~1.89). Compared with PLSR models, the performance of the RF models was more stable in the prediction of AGB in the training dataset (R2 = 0.95~0.97, RMSE = 0.58~1.08 t/ha, MAE = 0.46~0.89 t/ha, and RPD = 3.95~6.35) and validation dataset (R2 = 0.83~0.93, RMSE = 0.93~2.34 t/ha, MAE = 0.72~2.01 t/ha, RPD = 1.36~3.79). Monitoring AGB prior to flowering was found to be more effective than post-flowering. Moreover, this study demonstrates that it is feasible to estimate AGB for multiple growth stages of winter wheat by combining the optimal VIs and PLSR and RF models, which overcomes the saturation problem of using individual VI-based linear regression models.

Xanthine oxidase (XO) is a crucial enzyme in the development of hyperuricemia and gout. This study focuses on LWM and ALPM, two food-derived inhibitors of XO. We used molecular docking to obtain three systems and then conducted 200 ns molecular dynamics simulations for the Apo, LWM, and ALPM systems. The results reveal a stronger binding affinity of the LWM peptide to XO, potentially due to increased hydrogen bond formation. Notable changes were observed in the XO tunnel upon inhibitor binding, particularly with LWM, which showed a thinner, longer, and more twisted configuration compared to ALPM. The study highlights the importance of residue F914 in the allosteric pathway. Methodologically, we utilized the perturbed response scan (PRS) based on Python, enhancing tools for MD analysis. These findings deepen our understanding of food-derived anti-XO inhibitors and could inform the development of food-based therapeutics for reducing uric acid levels with minimal side effects.

Amyloid plaques and neurofibrillary tangles are pathologic hallmarks of Alzheimer’s disease (AD). Endoplasmic reticulum (ER) stress has been implicated in the loss of neurons in AD. The phosphatase and tensin homolog deleted on chromosome ten (PTEN) plays an important role in regulating neuronal survival processes. However, the direct effects of the PTEN on ER stress and apoptosis in AD have not been elucidated. In this study, we demonstrate that the expression of PTEN and ER stress related proteins, GRP78 and CHOP, increased in APP/PS1 transgenic AD mice compared with WT mice. A PTEN inhibitor, dipotassium bisperoxo-(5-hydroxypyridine-2-carboxyl)-oxovanadate (bpv) could decrease apoptosis, induce AKT phosphorylation and inhibit the ER stress response proteins in hippocampus in APP/PS1 transgenic AD model mice. Furthermore, treatment with the specific PI3K inhibitor, LY294002, significantly blocked the anti-apoptotic effects of bpv in AD mice. The expression in GRP78, CHOP and apoptosis levels by bpv was reversed after PI3K inhibitor treatment. Taken together, our results indicate that the neuroprotective role of bpv involves the suppression of ER stress via the activation of the PI3K/AKT signalling pathways in APP/PS1 transgenic AD model mice.

Wheat seedlings are becoming popular for its high nutritional value. Effects of White (W), White + Red (WR), and White + Blue (WB) light-emitting diodes (LEDs) treatments on growth, nutritional characteristics and antioxidant properties of wheat seedlings were studied in a plant factory. The results showed that height, leaf area, shoot fresh, and shoot dry weight per wheat seedling were the highest under WR at 13 and 22 days after planting. Soluble sugar content in leaves and stems were 22.3 and 65% respectively higher under WB than those under W. Soluble protein content in leaves and stems were 36.8 and 15.2% respectively lower under WR than those under W. Contents of total flavonoids, glutathione (GSH) and ascorbic acid (ASA) in leaves were the highest under WB, whereas malondialdehyde (MDA) content in leaves was the lowest under WB. The activities of antioxidant enzymes [superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX)] in leaves and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability were also the highest under WB. In conclusion, WR promoted the growth of wheat seedlings, and WB promoted antioxidant level and nutritional accumulation. This study provides guidance for wheat seedlings to carry out preferential production (biomass or quality).