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Abstract Background Depression and chronic constipation often co-occur, but the reciprocal influence between the two remains unclear. The purpose of this study is to explore the potential association between depression and chronic constipation. Methods This study initially utilized data from National Health and Nutrition Examination Survey (NHANES) 2005–2010 to explore the correlation between depression scores and chronic constipation, assessing the non-linear relationship between the two. Subsequently, we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal relationship between depression and major depression with chronic constipation. The Inverse Variance Weighting (IVW) method served as the primary reference, supplemented by sensitivity tests. Finally, a reverse MR analysis was performed to assess the presence of any reverse causation. The STROBE-MR checklist for the reporting of MR studies was used in this study. Results In the NHANES analysis, survey-weighted logistic regression revealed a significantly positive correlation between depression scores and chronic constipation (OR = 1.04, 95% CI = 1.02–1.07, p = 0.002), even after adjusting for the included covariates. The nonlinear analysis using Restricted Cubic Splines (RCS) enhanced the robustness of the association (P-non-liner = 0.01). The MR analysis also confirmed the causal relationship between depression (OR = 11.43, 95% CI = 1.85–70.67, p = 0.008) and major depression (OR = 1.12, 95% CI = 1.03–1.22, p = 0.007) with chronic constipation, passing rigorous sensitivity tests. No evidence of reverse causation was observed in the reverse MR analysis (P > 0.05). Conclusions Depression is positively correlated with the risk of chronic constipation. Therefore, enhancing attention to chronic constipation in patients with depression may be effective in clinical practice.

Millet is one of the major coarse grain crops in China. Its geographical origin and Fusarium fungal contamination with ergosterol and deoxynivalenol have a direct impact on food quality, so the rapid prediction of the geographical origins and fungal toxin contamination is essential for protecting market fairness and consumer rights. In this study, 600 millet samples were collected from twelve production areas in China, and traditional algorithms such as random forest (RF) and support vector machine (SVM) were selected to compare with the deep learning models for the prediction of millet geographical origin and toxin content. This paper firstly develops a deep learning model (wavelet transformation-attention mechanism long short-term memory, WT-ALSTM) by combining hyperspectral imaging to achieve the best prediction effect, the wavelet transformation algorithm effectively eliminates noise in the spectral data, while the attention mechanism module improves the interpretability of the prediction model by selecting spectral feature bands. The integrated model (WT-ALSTM) based on selected feature bands achieves optimal prediction of millet origin, with its accuracy exceeding 99% on both the training and prediction datasets. Meanwhile, it achieves optimal prediction of ergosterol and deoxynivalenol content, with the coefficient of determination values exceeding 0.95 and residual predictive deviation values reaching 3.58 and 3.38 respectively, demonstrating excellent model performance. The above results suggest that the combination of hyperspectral imaging with a deep learning model has great potential for rapid quality assessment of millet. This study provides new technical references for developing portable and rapid hyperspectral imaging inspection technology for on-site assessment of agricultural product quality in the future.

In this paper, we introduce MP-GT, a novel Graph Neural Network model that leverages meta-path-guided optimization within the GCN-Transformer framework to enhance application (App) usage prediction accuracy. Our approach addresses issues such as suspended animation and over-smoothing by extracting both local subgraph structures and global graph structures using a combination of GCN and Transformer method. Furthermore, we enhance the capture of semantic information and App usage patterns by incorporating a meta path-guided objective function. Extensive experiments demonstrate that MP-GT outperforms the widely adopted baseline of semantic-aware representation learning via Graph Convolutional Network (SA-GCN) by 13.33% in terms of Accuracy@1. Additionally, MP-GT surpasses the popular baseline of context-aware App usage prediction with heterogeneous graph embedding (CAP) by 74.02% in the same metric. Moreover, MP-GT reduces training time by 79.47% compared to SA-GCN. These findings validate that our approach not only achieves higher prediction accuracy but also converges faster than the baseline models. Therefore, MP-GT proves to be an effective and superior solution for the App usage prediction task.

Summary: Cell fate conversion is associated with extensive post-translational modifications (PTMs) and architectural changes of sub-organelles, yet how these events are interconnected remains unknown. We report here the identification of a phosphorylation code in 14-3-3 binding motifs (PC14-3-3) that greatly stimulates induced cardiomyocyte (iCM) formation from fibroblasts. PC14-3-3 is identified in pivotal functional proteins for iCM reprogramming, including transcription factors and chromatin modifiers. Akt1 kinase and protein phosphatase 2A are the key writer and key eraser of the PC14-3-3 code, respectively. PC14-3-3 activation induces iCM formation with the presence of only Tbx5. In contrast, PC14-3-3 inhibition by mutagenesis or inhibitor-mediated code removal abolishes reprogramming. We discover that key PC14-3-3-embedded factors, such as histone deacetylase 4 (Hdac4), Mef2c, and Foxo1, form Hdac4-organized inhibitory nuclear condensates. PC14-3-3 activation disrupts Hdac4 condensates to promote cardiac gene expression. Our study suggests that sub-organelle dynamics regulated by a PTM code could be a general mechanism for stimulating cell reprogramming.

The influence of sensitization on the precipitation behaviour and environmentally assisted cracking (EAC) of AA5083 alloy with the –H128 temper have been investigated. 80 °C/500 h and 80 °C/1000 h sensitized specimens exhibit discontinuous Mg-rich precipitates along the grain boundaries, whereas almost continuous β′ phase is present along the grain boundaries in the 175 °C/100 h sensitized material. EAC susceptibility increases with increasing exposure time and elevated temperature. The relationship between nitric acid mass loss test (NAMLT) values and mechanical test results indicates that specimens with a NAMLT value greater than 25 mg/cm2 exhibit severe EAC. The test environment affects the degree of EAC due to the combined effects of anodic dissolution at the crack tip, hydrogen evolution, and hydrogen embrittlement. AA5083-H128 exhibits lower EAC susceptibility than AA5083-H131, likely due to its lower yield strength. High yield strength can produce more Mg-rich precipitates after sensitization, increase the constraint of the crack tip material and accelerate the diffusion rate of H atoms in the process zone of the crack tip.

Abstract Background Homosexual contact is the main route of human immunodeficiency virus type one (HIV-1) transmission in Cangzhou Prefecture, Hebei, China. Moreover, the number of circulating recombinant forms (CRFs) and unique recombinant forms (URFs) in this key population is ever increasing. Methods In this study, we identified two novel URFs (hcz0017 and hcz0045) from two men who have sex with men (MSM) based in Cangzhou Prefecture. Phylogenetic and recombinant breakpoint analyses, based on the near full-length genomes (NFLGs) of the two novel URFs, showed that they originated from a recombination between HIV-1 CRF01_AE and subtype B. Results HXB2 numbering revealed that the NFLGs of hcz0017 and hcz0045 each contained the following seven subregions: hcz0017: IB (790–1,171 nt), IICRF01_AE (1,172–2,022 nt), IIIB (2,023–4,469 nt), IVCRF01_AE (4,470–5,866 nt), VB (5,867–7,462 nt), VICRF01_AE (7,463–8,379 nt), VIIB (8,380–9,411 nt); hcz0045: ICRF01_AE (790–5,147 nt), IIB (5,148–5,614 nt), IIICRF01_AE (5,615–6,035 nt), IVB (6,036–6,241 nt), VCRF01_AE (6,242–7,325nt), VIB (7,326–8,254 nt), VIICRF01_AE (8,255–9,411 nt). Moreover, the two MSM from whom the novel URFs originated from were diagnosed as recently HIV-1-infected, suggesting that the high prevalence of HIV-1 among MSM was related to high-risk sexual activity such as unprotected anal sex and multiple sexual partners. Conclusions Our results highlight the need to continually monitor HIV-1 diversity in Hebei and its neighboring provinces to achieve a more effective control of HIV-1 spread within the MSM community.

Abstract Human epidermal growth factor receptor 2 (HER2) possesses tyrosine kinase activity and participates in cell growth, differentiation and migration, and survival. Its alterations, mainly including mutations, amplifications, and overexpression are associated with poor prognosis and are one of the major drivers in non–small cell lung cancer (NSCLC). Several clinical trials had been investigating on the treatments of HER2‐altered NSCLC, including conventional chemotherapy, programmed death 1 (PD‐1) inhibitors, tyrosine kinase inhibitors (TKIs) and antibody‐drug conjugates (ADCs), however, the results were either disappointing or encouraging, but inconsistent. Trastuzumab deruxtecan (T‐DXd) was recently approved by the Food and Drug Administration as the first targeted agent for treating HER2‐mutant NSCLC. Effective screening of patients is the key to the clinical application of HER2‐targeted agents such as TKIs and ADCs. Various testing methods are nowadays available, including polymerase chain reaction (PCR), next‐generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), etc. Each method has its pros and cons and should be reasonably assigned to appropriate patients for diagnosis and guiding treatment decisions. To help standardize the clinical workflow, our expert group reached a consensus on the clinical management of HER2‐altered NSCLC, focusing on the diagnosis and treatment strategies.

Abstract Immune checkpoint inhibitors (ICIs) have successfully treated a number of different types of cancer, which is of great significance for cancer treatment. With the widespread use of ICIs in clinical practice, the increasing checkpoint inhibitor pneumonia (CIP) will be a challenge to clinicians. To guide the diagnosis and treatment of CIP, we conducted in‐depth discussions based on the latest evidence, forming a consensus among Chinese experts on the multidisciplinary management of CIP.

Abstract Background To date, the optimal treatment for potentially resectable metastatic colorectal cancer (mCRC) patients has yet to be determined. Encouraging results have been reported in studies exploring the efficacy of triplet chemotherapy plus anti-epidermal growth factor receptor (anti-EGFR) target agents. Thus, we conducted a meta-analysis to evaluate the efficacy and safety of triplet chemotherapy plus anti-EGFR target agents. Methods We systematically searched the PubMed, Embase, and Web of Science databases from December 2004 to October 2021 for studies examining the efficacy of triplet chemotherapy plus anti-EGFR target agents in mCRC patients. The primary outcomes were the objective response rate (ORR) and R0 resection rate (R0RR), and the secondary outcomes were median progression-free survival (mPFS), median overall survival (mOS), and toxicity. Data were analyzed with R software 4.1.2. Results Fourteen studies comprising 762 patients with mCRC were included in this meta-analysis. Analysis with a random effects model revealed that after treatment with triplet chemotherapy plus anti-EGFR target agents, the pooled ORR was 82% (95% CI= 76–88%, I 2= 76%), and the pooled R0RR of colorectal liver metastasis (CLM) was 59% (95% CI= 49–68%, I 2= 60%). The mPFS ranged from 9.5 to 17.8 months, and the mOS ranged from 24.7 to 62.5 months. A total of 648 grade 3 or 4 adverse events were reported; the most commonly reported events were diarrhea (174/648), neutropenia (157/648), and skin toxicity (95/648), which had pooled prevalence rates of 29% (95% CI= 20–39%, I 2= 84%), 28% (95% CI= 20–37%, I 2= 77%), and 17% (95% CI= 11–24%, I 2= 66%), respectively. Conclusions Triplet chemotherapy plus anti-EGFR agents therapy seems to be capable of increasing the ORR of mCRC patients and the R0RR of CLM patients. The toxicity of this treatment is manageable. High-quality randomized controlled trial (RCT) studies are required for further validation.

A nomogram was constructed to predict the survival of patients with colorectal mucinous adenocarcinoma based on data extracted from the Surveillance, Epidemiology and End Result (SEER) database. Data collected between 2010 and 2018 were obtained from the SEER database. The log-rank test and multivariate Cox regression were performed to identify the independent prognostic factors for overall survival, which were further used to construct a nomogram model to predict 1-, 3-, and 5-year overall survival. In total, 10846 patients diagnosed with colorectal mucinous adenocarcinoma were enrolled in the study. The following 11 variables were associated with survival and were further incorporated into the nomogram: age at diagnosis, primary site, grade, tumour size, lymph node dissection, T stage, N stage, M stage, surgery for primary site, chemotherapy, and household income. The concordance index (C-index) value was 0.725 (95% confidence interval 0.716-0.734), and the receiver operating characteristic curves and calibration curves showed satisfactory predictive accuracy. Both the C-index and time-independent area under the curve values were greater than those of the American Joint Committee on Cancer 7th TNM classification system (both P < 0.001). In the validation group, the results were consistent with those of the training group, with a C-index value of 0.726 (95% confidence interval 0.713-0.739). This study constructed a practical nomogram to predict 1-, 3-, and 5-year OS for patients with colorectal colorectal mucinous adenocarcinoma based on SEER data.

This paper investigated the Mg-rich phase precipitation behavior and the corrosion performance throughout the thickness direction within the stirred zone (SZ) of friction stir welded (FSW) AA5083 alloy after 175 °C/100 h sensitization. For the as-welded SZ, the recrystallized grain size gradually decreased from the top surface (5.5 μm) to the bottom (3.7 μm). The top and bottom of the SZ maintained relatively high levels of deformed grains and accumulated strain induced by either shoulder pressing or pin stirring. After 175 °C/100 h sensitization, 100 nm thick β′-Al3Mg2 precipitates were present along the grain boundaries (GBs) in the SZ. The bottom of the SZ exhibited more continuous precipitates along GBs due to the fine grain size and the large fraction of high-angle grain boundaries (0.724%). Although the as-welded SZ exhibited excellent corrosion resistance, it became extremely vulnerable to intergranular cracking (IGC) and stress corrosion cracking (SCC) after sensitization. The large SCC susceptibility indices of the SZ samples ranged from 66.9% to 73.1%. These findings suggest that sensitization can strongly deteriorate the corrosion resistance of the Al-Mg FSW joint, which is of critical importance for the safety and reliability of marine applications.

Early childhood development intervention has gained considerable achievements in eliminating intergenerational transmission of poverty in rural areas. Paying further attention to rural children’s community inclusion can also promote the sustainable development of the village. However, there is a lack of systematic theoretical constructs on the village inclusion of rural children. In this study, an attempt was made to explore the problem mechanism and solution strategy of community inclusion of rural children using a grounded theory approach of in-depth interviews. Seventeen parents of children in a national-level poverty-stricken county in Inner Mongolia of China were investigated, adopting the strategy of intensity sampling. The results revealed that (1) the content of rural children’s activities demonstrates enhanced participation in the virtual environment and weakened participation in the real community environment. That is, the activities are characterized by more virtualization and individualization. (2) Rural parents and community peers are two major channels for children’s community inclusion, while both the community peer environment and parental community participation show a weakening trend. This may be an important reason for the virtualization and individualization of the children’s psychological development environment. (3) Developmental intervention programs for rural children in poverty-stricken areas should focus on the reconstruction of children’s community peer environment, encourage the community participation of parents, and fully mobilize local-based educational resources.

Myocardial infarction (MI) is accompanied by severe energy deprivation and extensive epigenetic changes. However, how energy metabolism and chromatin modifications are interlinked during MI and heart repair has been poorly explored. Here, we examined the effect of different carbon sources that are involved in the major metabolic pathways of acetyl-CoA synthesis on myocardial infarction and found that elevation of acetyl-CoA by sodium octanoate (8C) significantly improved heart function in ischemia reperfusion (I/R) rats. Mechanistically, 8C reduced I/R injury by promoting histone acetylation which in turn activated the expression of antioxidant genes and inhibited cardiomyocyte (CM) apoptosis. Furthermore, we elucidated that 8C-promoted histone acetylation and heart repair were carried out by metabolic enzyme medium-chain acyl-CoA dehydrogenase (MCAD) and histone acetyltransferase Kat2a, suggesting that 8C dramatically improves cardiac function mainly through metabolic acetyl-CoA-mediated histone acetylation. Therefore, our study uncovers an interlinked metabolic/epigenetic network comprising 8C, acetyl-CoA, MCAD, and Kat2a to combat heart injury.

Abstract Background A stroke caused by angiostenosis always has a poor prognosis. Bone marrow stromal cells (BMSC) are widely applied in vascular regeneration. Recently, thrombospondin-4 (TSP4) was reported to promote the regeneration of blood vessels and enhance the function of endothelial cells in angiogenesis. In this work, we observed the therapeutic effect of TSP4-overexpressing BMSCs on angiogenesis post-stroke. Methods We subcloned the tsp4 gene into a lentivirus expression vector system and harvested the tsp4 lentivirus using 293FT cells. Primary BMSCs were then successfully infected by the tsp4 virus, and overexpression of GFP-fused TSP4 was confirmed by both western blot and immunofluorescence. In vitro, TSP4-overexpressing BMSCs and wild-type BMSCs were co-cultured with human umbilical vein endothelial cells (HUVECs). The expression level of TSP4, vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Wound healing, tube formation and an arterial ring test were performed to estimate the ability of TSP4-overexpressing BMSCs to promote the angiogenesis of endothelial cells. Using a rat permanent middle cerebral artery occlusion (MCAO) model, the effect of TSP4-overexpressing BMSCs on the regeneration of blood vessels was systematically tested by the neurological function score, immunohistochemistry and immunofluorescence staining assays. Results Our results demonstrated that TSP4-overexpressing BMSCs largely increased the expression of VEGF, angiopoietin-1 (Ang-1), matrix metalloprotein 9 (MMP9), matrix metalloprotein 2 (MMP2) and p-Cdc42/Rac1 in endothelial cells. TSP4-BMSC treatment notably up-regulated the TGF-β/Smad2/3 signalling pathway in HUVECs. In vivo, the TSP4-BMSC infusion improved the neurological function score of MCAO rats and expanded the expression of the von Willebrand factor (vWF), Ang-1, MMP2 and MMP9 proteins in cerebral ischemic penumbra. Conclusions Our data illustrate that TSP4-BMSCs can promote the proliferation and migration of endothelial cells and tube formation. We found that TSP4-BMSC infusion can promote the recovery of neural function post-stroke. The tsp4 gene-modified BMSCs provides a better therapeutic effect than that of wild-type BMSCs.

Extensive Early Permian mafic-ultramafic intrusions, doleritic dykes, and basalts crop out within the Beishan area, southern Central Asian Orogenic Belt (CAOB). We present new geochronological and geochemical data for Gubaoquan dolerite dyke swarms in the Beishan orogenic belt. Zircon U-Pb Dating of the Gubaoquan dykes indicates that they were emplaced during the Early Permian (280.7 ± 4 Ma), that was coeval with Yinaoxia and Podong mafic dykes in Beishan area. The dykes are characterized by low Mg# (47–84) in the clinopyroxene crystals, and the content of whole-rock Fe2O3 (t), MgO, and alkali (Na2O + K2O) range from 12.5–17.4, 4.06–5.51, and 2.8–4.4 wt.%, respectively. The samples from the Gubaoquan dykes have high and variable Ba/La (5.93–14.2) and Ba/Nb (15.0–37.3) ratios but low Th/Yb (0.17–0.24) ratios. The rocks show slightly enrichments in LREE, HFSE, Th, and Hf, and depletion in Nb and Ta. The εNd (t = 280 Ma) values and initial 87Sr/86Sr ratios of the Gubaoquan dykes show variations ranging from 6.4 to 6.8 and 0.706240 to 0.707546, respectively. These data suggest that the parental magmas for the Gubaoquan dykes were probably derived from partially decompressed melting of upwelling depleted asthenosphere mantle that was metasomatized previously by subducted fluids.

Potato late blight, caused by Phytophthora infestans (Mont.) de Bary, represents a great food security threat worldwide and is difficult to control. Recently, Bacillus spp. have been considered biocontrol agents to control many plant diseases. Here, Bacillus subtilis WL-2 was selected as a potent strain against P. infestans mycelium growth, and its functional metabolite was identified as Iturin A via electrospray ionization mass spectrometry (ESI-MS). Analyses using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that Iturin A caused cell membrane disruption and an irregular internal cell structure. In addition, Iturin A triggered oxidative stress reactions similarly to reactive oxygen species (ROS) in P. infestans cells and caused mitochondrial damage, including mitochondrial membrane potential (MMP), mitochondrial respiratory chain complex activity (MRCCA), and ATP production decline. These results highlight that the cell structure disruption, oxidative stress, and energy supply dysfunction induced by Iturin A play an important role in inhibiting P. infestans. Additionally, B. subtilis WL-2 and Iturin A have great potential for inhibiting P. infestans mycelium growth and controlling potato late blight in the future.

Objective Patients with non-small-cell lung cancer (NSCLC) and primary or acquired resistance do not respond to targeted drugs. We explored whether cancer cells can be cultured from liquid biopsies from patients with primary resistance to tyrosine kinase inhibitors (TKIs). We aimed to predict patients’ responses to drugs according to in vitro drug testing results. Methods Cancer cell cultures were established from the pleural effusion of a patient with TKI-resistant NSCLC using a conditional reprogramming technique. Phenotypic drug sensitivity tests were performed using the Cell Counting Kit-8 assay. We tested individual drugs and compared the synergistic and inhibitory effects of drug combinations. Results The results of our in vitro sensitivity test using the combination of cisplatin and pemetrexed were correlated with the patient’s response. Conclusion This represents the first successful report of predictive testing for combination therapy in patients with epidermal growth factor receptor-mutant NSCLC and primary TKI resistance. This strategy should be applicable to both chemotherapies and targeted therapies, and it will significantly improve the clinical treatment and management of patients with NSCLC and primary or acquired resistance to targeted therapies, as well as patients lacking targetable mutations.

Oomycete Phytophthora infestans [(Mont.) de Bary] is the cause of potato late blight, a plant disease which poses a serious threat to our global food security and is responsible for huge economic losses worldwide. Lipopeptides produced by Bacillus species are known to be potent antibacterial compounds against many plant pathogens. In this study, we show that Bacillus megaterium WL-3 has an antagonistic effect against potato late blight. Electrospray ionization mass spectrometry (ESI-MS) revealed that lipopeptides derived from the WL-3 strain contained three subfamilies, surfactin (C13 – C15), Iturin A (C14 – C16), and Fengycin A (C15 – C19). The Iturin A and Fengycin A lipopeptide families were each confirmed to have anti-oomycete effects against P. infestans mycelium growth as well as obvious controlling effects against potato late blight in greenhouse experiments and field assays. Furthermore, Iturin A and Fengycin A were able to promote plant photosynthetic efficiency, plant growth, and potato yield. Most importantly, the combination of Iturin A and Fengycin A (I + F) was superior to individual lipopeptides in controlling potato late blight and in the promotion of plant growth. The results of this study indicate that B. megaterium WL-3 and its lipopeptides are potential candidates for the control of late blight and the promotion of potato plant growth.

Background: Epigenetic histone acetylation is a major event controlling cell functions, such as metabolism, differentiation and repair. Here, we aim to determine whether Valproic acid (VPA), a FDA approved inhibitor of histone deacetylation for bipolar disease, could protect heart against myocardial infarction (MI) injury and elucidate key molecular pathways. Methods: VPA was administrated to MI rats at different time points, onset and after MI injury. Echocardiography, histology, serum biology assays, and gene expression, inhibition, and over-expression were performed to characterize the systolic function, infarct size, gene and signaling pathways. Findings: VPA treatment reduced the infarct size by ~50% and preserved the systolic function of heart after acute MI in rats. Even 60 min after infarction, VPA treatment significantly decreased infarct size. Furthermore, long-term treatment of VPA markedly improved myocardial performance. VPA regulated gene expression essential for cell survival and anti-inflammatory response. Consequently, oxidative stress and cell death were notably reduced after VPA treatment. Moreover, Foxm1 was identified as a potential key target of VPA. Overexpression of Foxm1 provided similar heart protective effect to VPA treatment. Particularly, both VPA treatment and Foxm1 over-expression repressed inflammatory response after MI for heart protection. In contrast, inhibition of Foxm1 activity abolished the cardiac protective effect of VPA. VPA mediated CM protection through Foxm1 upregulation was also identified in a human ESC derived CM hypoxia/reperfusion system. Interpretation: VPA treatments significantly reduce cardiac damage after MI and the cardioprotective effect of VPA is likely mediated via Foxm1 pathway. Fund: This work was mainly supported by 1R01HL109054. Keywords: Valproic acid, Myocardial infarction, Foxm1, Cardiomyocyte protection

From the marine-derived fungus Penicillium sumatrense (Trichocomaceae), a pair of enantiomers [(+)-1 and (−)-1] were isolated with identical 1D NMR data to drazepinone, which was originally reported to have a trisubstituted naphthofuroazepinone skeleton. In this study, we confirmed the structures of the two enantiomers as drazepinone and revised their structures by detailed analysis of extensive 2D NMR data and a comparison of the calculated 13C chemical shifts, ECD, VCD, and ORD spectra with those of the experiment ones. (+)-1 and (−)-1 were evaluated for their PTP inhibitory activity in vitro. (−)-1 showed selective PTP inhibitory activity against PTP1B and TCPTP with IC50 values of 1.56 and 12.5 μg/mL, respectively.

Infections of emerging and reemerging viruses (SARS-CoVs, influenza H1N1, etc.) largely and globally affect human health. Animal models often fail to reflect a physiological status because of species tropism of virus infection. Conventional cell lines are usually genetically and phenotypically different from primary cells. Developing an in vitro physiological model to study the infection of emerging viruses will facilitate our understanding of virus-host cell interactions, thereby benefiting antiviral drug discovery. In the current work, we first established normal airway epithelial cells (upper and lower airway track) in 2D and 3D culture systems using conditional reprogramming (CR) and air-liquid interface (ALI) techniques. These long-term cultures maintained differentiation potential. More importantly, these cells express two types of influenza virus receptors, α2-6-Gal- and α2-3-Gal-linked sialic acids, and angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoVs as well. These cells were permissive to the infection of pandemic influenza H1N1 (H1N1pdm). In contrast, the lung cancer cell line A549 and immortalized airway epithelial cells (16HBE) were not susceptible to H1N1 infection. A virus-induced cytopathic effect (CPE) on 2D CRC cultures developed in a time-dependent manner. The pathological effects were also readily observed spreading from the apical layer to the basal layer of the 3D ALI culture. This integrated 2D CRC and 3D ALI cultures provide a physiological and personalized in vitro model to study the infection of emerging viruses. This novel model can be used for studying virus biology and host response to viral infection and for antiviral drug discovery.

Inverse synthetic aperture radar (ISAR) is an important tool for non-cooperative ship imaging, and one key step of ISAR imaging is range alignment. To achieve the range alignment with high precision, efficiency and robustness, an improved ISAR range alignment method based on maximum contrast is proposed in this paper, which takes the maximum contrast of average range profile as the optimisation criterion to perform the range alignment. Compared with the minimum entropy method, this method is with lower computation complexity and faster convergence rate. Thus the method proposed in this article is more effective and more robust. Computer simulation and real data experiment validate the effectiveness and robustness of the proposed method.

The receptor for advanced glycation end products (RAGE) is involved in heart failure (HF) by mediating diverse pathologic processes, including the promotion of inflammation and autophagy. However, the role of RAGE in pressure overload-induced HF is not well understood. We found that stimulation of RAGE triggered the death of neonatal rat ventricular myocytes (NRVMs), while cell death was alleviated by ATG5 knockdown. Using transverse aortic constriction (TAC) in mice as a model of pressure overload-induced HF, we demonstrated that RAGE knockout or RAGE blockade attenuated cardiac hypertrophy and fibrosis as well as cardiac dysfunction at 8 weeks after TAC. Importantly, RAGE knockout reversed upregulation of autophagy related proteins (LC3BII/I and Beclin 1) and reduced cardiomyocyte death, indicating that excessive autophagy after TAC was inhibited. Moreover, RAGE knockout or blockade reduced the upregulation of pp65-NFκB and BNIP3, which mediate autophagy. Taken together, these results suggest that RAGE plays an important role in the progression of HF by regulating autophagy. Therefore, inhibition of the RAGE-autophagy axis could be a promising new strategy for treatment of heart failure.

Neurofibrillary pathology contributes to neuronal dysfunction and correlates with the clinical progression of Alzheimer’s disease (AD). Tau phosphorylation is mainly regulated by a balance of glycogen synthase kinase-3β (GSK-3β) and protein phosphatase 2A (PP2A) activities. Cornel iridoid glycoside (CIG) is a main component extracted from Cornus officinalis. The purpose of this study was to investigate the effects of CIG on GSK-3β and PP2A, thus to explore the mechanisms of CIG to inhibit tau hyperphosphorylation. The rat model of tau hyperphosphorylation was established by intraventricular injection of wortmannin and GF-109203X (GFX) to activate GSK-3β. The results showed that intragastrical administration of CIG inhibited tau hyperphosphorylation in the brain of rats induced by wortmannin/GFX. The results in vivo and in vitro exhibited that CIG inhibited tau hyperphosphorylation and GSK-3β over-activation. In the mechanism of action, CIG’s attenuating GSK-3β activity was found to be dependent on PI3K/AKT signaling pathway. PP2A catalytic C subunit (PP2Ac) siRNA abrogated the effect of CIG on PI3K/AKT/GSK-3β. Additionally and crucially, we also found that CIG inhibited the demethylation of PP2Ac at Leu309 in vivo and in vitro. It enhanced PP2A activity, decreased tau hyperphosphorylation, and protected cell morphology in okadaic acid (OA)-induced cell model in vitro. PP2Ac siRNA abated the inhibitory effect of CIG on tau hyperphosphorylation. Moreover, CIG inhibited protein phosphatase methylesterase-1 (PME-1) and demethylation of PP2Ac, enhanced PP2A activity, and decreased tau hyperphosphorylation in PME-1-transfectd cells. Taken together, CIG inhibited GSK-3β activity via promoting P13K/AKT and PP2A signaling pathways. In addition, CIG also elevated PP2A activity via inhibiting PME-1-induced PP2Ac demethylation to inhibit GSK-3β activity, thus regulated the cross-talk between GSK-3β and PP2A signaling and consequently inhibited tau hyperphosphorylation. These results suggest that CIG may be a promising agent for AD therapy.

Self-care is important for type 2 diabetes mellitus (T2DM) patients' disease prognosis, but there is a common phenomenon of self-regulation failure in T2DMs. In order to figure this problem out, the current study explored the interaction between self-regulation resource depletion and diabetes self-care based on the limited resource model of self-regulation. 104 patients were surveyed using the Self-Regulatory Fatigue Scale (SRF-S) and the Diabetes Self-care Scale (DSCS) in study 1. Study 2 recruited 30 T2DM patients and 30 healthy controls, and used a sequential-task paradigm to test the effect of self-regulation resource depletion on them. Participants in study 3 were 60 T2DM patients under different levels of self-regulation resource depletion manipulation, and their self-regulation performance was recorded and compared. Study 1 indicated that the correlation between self-regulation resource depletion and exercise and diet was significant and negative, suggesting that patients with greater self-regulation resource depletion performed poorly in exercise and diet. In Study 2, T2DM patients exhibited a poorer performance on the Spatial Incompatibility Task than the participants in the control group, suggesting that their self-regulation resource was insufficient. Study 3 indicated that there was no difference in Spatial Incompatibility Task performance, reaction time or error number among patients who were requested to complete a dietary record for one week and patients who were only requested to record eating times. This research demonstrated that low levels of diabetes self-care execution was associated with patients' deficiency in self-regulatory resource, and self-care as a series of goal-directed behaviors consumed patients' self-regulatory resources before these behaviors became a habit.

We explored the development of attention among elementary school children. Three hundred and sixty-five primary school children aged 7–12 years completed seven attention tests (alertness, focused attention, divided attention, attentional switching, sustained attention, spatial attention, and supervisory attention). A factor analysis indicated that there was no stable construct of attention among 7- to 8-year-old children. However, from 9 years on, children’s attention could be separated into perceptual and executive attention. Notably, however, the attention types included in these two factors differed from those among adults.

Although ego depletion effects have been widely observed in experiments in which participants perform consecutive self-control tasks, the process of ego depletion remains poorly understood. Using the strength model of self-control, we hypothesized that chronic ego depletion adversely affects goal adherence and that mental effort and motivation are involved in the process of ego depletion. In this study, 203 students reported their daily performance, mental effort, and motivation with respect to goal directed behavior across a 3-week time period. People with high levels of chronic ego depletion were less successful in goal adherence than those with less chronic ego depletion. Although daily effort devoted to goal adherence increased with chronic ego depletion, motivation to adhere to goals was not affected. Participants with high levels of chronic ego depletion showed a stronger positive association between mental effort and performance, but chronic ego depletion did not play a regulatory role in the effect of motivation on performance. Chronic ego depletion increased the likelihood of behavior regulation failure, suggesting that it is difficult for people in an ego-depletion state to adhere to goals. We integrate our results with the findings of previous studies and discuss possible theoretical implications.

Objective: To analyze the psychological status of patients with acute cerebral infarction (ACI), and to evaluate the effect of positive psychological intervention on the treatment and prognosis of ACI. Methods: This was retrospective study. Eighty patients with ACI admitted to Institute of Psychology, Chinese Academy of Sciences from January 2021 to September 2022 were included and randomly divided into observation group (n=40) and control group(n=40). Patients in the control group received conventional treatment and routine care, while those in the observation group received positive psychological intervention based on the control group. Adverse psychological scores, treatment and prognosis, and quality of life as well as nursing satisfaction etc. were analyzed and compared between the two groups. Results: Both groups showed a significant decrease in SDS and SAS scores at three months after the intervention compared with the pre-intervention period, with a statistically significant difference(P<0.05). After the intervention, the NIHSS score of both groups decreased, with a statistically significant difference(P<0.05). The FMAS and MBI scores increased in both groups compared with those before the intervention, with a statistically significant difference(P<0.05). The SS-QOL scores of both groups were significantly improved compared with before the intervention, with a statistically significant difference(P<0.05). The hospital satisfaction rate in the observation group was significantly higher than that in the control group, with a statistically significant difference (t=12.325, P=0.000). Conclusion: Positive psychological intervention offers a variety of benefits in the treatment of patients with ACI, such as may alleviate anxiety and depression, reduce neurological deficits, improving quality of life and motor function, and ameliorate the prognosis of patients. [ABSTRACT FROM AUTHOR]