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Semantic segmentation techniques for remote sensing scene understanding have significantly advanced, enhancing the refined Earth observation. However, most methods highly depend on extensive annotated data, leading to performance deterioration in complex high-resolution remote sensing cross-domain scenes, where variations in image conditions and environments are prevalent. Domain adaptive semantic segmentation (DASS) has been proposed to mitigate the reliance on dense and costly annotations, typically using stagewise training. This article addresses three key challenges in existing DASS methods: 1) insufficient warmup training, limiting potential performance gains; 2) rigid pseudolabel threshold settings in self-training (ST) result in performance bottlenecks; 3) entropy-based prediction bias alone fails to effectively identify high-confidence noise early in ST. To address these issues, we propose a novel threshold-free pseudolabel learning framework, TPL-DA. During the warmup stage, we introduce a multiview bidirectional consistency learning mechanism within a teacher–student architecture. This mechanism employs a bias-free data augmentation strategy, fostering consistent bidirectional predictions in teacher–student networks, thereby enhancing domain generalization and feature robustness. Our multiscale context-enhanced prediction module further amplifies this. In the ST stage, we propose a dynamic threshold-free pseudolabel learning strategy that utilizes well-aligned feature prototypes in the feature space to guide pseudolabel generation in the probability space, eliminating the threshold constraints. In addition, we model uncertainty using relative entropy and incorporate it into the optimization objective to manage high-confidence noise. Extensive experiments on the LoveDA, Potsdam, and Vaihingen datasets demonstrate that TPL-DA consistently outperforms existing methods and popular benchmarks, significantly enhancing DASS performance across diverse cross-domain scenes.

Abstract Background Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. Despite advancements in therapeutic methodologies, it still causes a high rate of patient mortality. CD8+ tissue-resident memory T (TRM) cells are strategically positioned to mediate effective anti-tumor responses. However, the characteristic surface molecules and functions of CD8+ TRM cells exhibit significant heterogeneity. Methods The roles and anti-tumor biological functions of different CD8+ TRM subsets in CRC were determined by clinical CRC samples, bioinformatics analysis, and in vitro experiments including co-culture experiments and transwell migration assays. The signaling pathways that synergistically regulate the differentiation of CD8+ TRM cells were identified by in vitro CD8+ T cell activation and inhibition assays, and the functioning transcription factors were predicted using the UCSC and JASPAR databases. Results We found that different CD8+ TRM subsets existed in CRC tumor tissues, which were identified as CD69−CD103−CD8+ TRM, CD69+CD103−CD8+ TRM (SP CD8+ TRM), and CD69+CD103+CD8+ TRM (DP CD8+ TRM) subsets. Compared with SP CD8+ TRM cells, increased infiltration of DP CD8+ TRM cells predicted better prognosis and played a protective role mainly in tumor invasion and lymph node metastasis of CRC. DP CD8+ TRM cells expressed higher levels of effector molecules and exerted stronger anti-tumor effects in a FAS/FASL pathway-dependent manner. Additionally, DP CD8+ TRM cells secreted higher levels of CXCL13 and recruited B cells into tumor tissues through the CXCL13/CXCR5 signaling axis to form tertiary lymphoid structures, participating in anti-tumor immune responses. Notch and TGF-β signaling pathways synergistically regulate the differentiation of DP CD8+ TRM cells. Conclusions We clarified the roles and mechanisms of different CD8+ TRM subsets in CRC and identified that DP CD8+ TRM cells exert stronger anti-tumor effects and predict better prognosis, which provides ideas for developing new clinically available therapeutic targets.

Abstract Background Invasive pulmonary aspergillosis (IPA) is a serious fungal infection. However, current diagnostic methods have limitations. The purpose of this study was to use artificial intelligence to achieve a more accurate diagnosis of IPA. Methods Totally 263 patients (148 cases of IPA, 115 cases of non-IPA) were retrospectively enrolled from a single institution and randomly divided into training and test sets at a ratio of 7:3. Clinic-radiological independent risk factors for IPA were screened using univariate analysis and multivariate logistic regression analysis, after which a clinic-radiological model was constructed. The optimal radiomics features were extracted and screened based on CT images to construct the radiomics label score (Rad-score) and radiomics model. The optimal DL features were extracted and screened using four pre-trained convolutional neural networks, respectively, followed by the construction of the DL label score (DL-score) and DL model. Then, the radiomics-DL model was constructed. Finally, the combined model was constructed based on clinic-radiological independent risk factors, the Rad-score, and the DL-score. LR was adopted as the classifier. Receiver operating characteristic (ROC) curves were drawn, and the areas under the curve (AUC) were calculated to evaluate the efficacy of each model in predicting IPA. Additionally, based on the best-performing model on the LR classifier, four other machine learning (ML) classifiers were constructed to evaluate the predictive value for IPA. Results The AUC of the clinic-radiological model for predicting IPA in the training and test sets was 0.845 and 0.765, respectively. The AUC of the radiomics-DL and combined models in the training set was 0.871 and 0.932, while in the test set was 0.851 and 0.881, respectively. The combined model showed better predictive performance than all other models. DCA showed that taking 0.00–1.00 as the threshold, the clinical benefit of the combined model was higher than that of all other models. Then, the combined model was trained on four other machine learning classifiers, all of which achieved AUC values above 0.80 in the test set, showing good performance in predicting IPA. Conclusion Clinic, CT radiomics, and DL combined model could be used to predict IPA effectively.

Abstract The specific mechanisms underlying effector pathways in autoimmune liver disease remain enigmatic and therefore constructing appropriate murine models to investigate disease pathogenesis becomes critical. A spontaneous severe murine model of autoimmune liver disease has been previously established in dnTGFβRII Aire−/− mice, exhibiting disease phenotypes that resemble both human primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). The data suggests that auto‐reactive liver‐specific CD8+ T cells are the primary pathogenic cells in liver injury. In this study, these data are advanced through the use of both single‐cell sequencing and extensive in vitro analysis. The results identify a specific expanded pathogenic subset of PD‐1+CD8+ T cells in the liver, exhibiting strong functional activity and cytotoxicity against target cells. Depletion of PD‐1+CD8+ T cells using CAR‐T cells effectively alleviates the disease. GSDMD‐mediated pyroptosis is found to be aberrantly activated in the livers of model mice, and treatment with a GSDMD‐specific inhibitor significantly inhibits disease progression. In vitro experiments reveal that PD‐1+CD8+ T cells can induce the pyroptosis of hepatocytes through elevated production of granzyme B and perforin‐1. These results provide a novel explanation for the cytotoxic activity of pathogenic liver PD‐1+CD8+ T cells in autoimmune liver diseases and offer potential therapeutic targets.

BackgroundSentinel lymph node biopsy (SLNB) has become standard procedure for early breast cancer patients with clinically node negative disease. The patients with SLN metastasis normally underwent axillary lymph node dissection (ALND). However, the metastatic status of non-sentinel Lymph nodes (non-SLNs) varied significantly in different reports. Here, we evaluated the prevalence of non-SLNs metastasis among breast cancer patients with sentinel lymph node metastasis and its impact on clinical decision-making.Materials and MethodsWe identified 892 female patients with operable cT1-3N0 invasive breast cancer who underwent ALND in our center due to SLN metastasis from 2017 to 2023, retrospectively. The prevalence of non-SLN metastasis among different clinicopathological traits and its correlation with the number of positive SLNs were analyzed. The optimal clinical decision-making was generalized.ResultsThe median number of SLN+, SLN, non-SLN+ and non-SLN was 2, 4, 1 and 14 among the enrolled 892 female patients, respectively. 504 (56.50%) patients with SLN + had at least one metastatic lymph node in the harvested non-SLNs. Among the enrolled 892 female patients, 435 (48.77%) patients with 1 positive SLN, of which 180 (41.38%) had at least one additional metastatic non-SLNs. 242 (27.13%) patients with 2 positive SLNs, of which 146 (60.33%) had at least one metastatic non-SLNs. For the rest 215 (24.10%) patients with at least 3 metastatic SLNs, 178 (82.79%) had at least one metastatic non-SLNs. In the univariate analysis, the non-SLNs metastatic status was correlated with the number of SLNs+, tumor size, tumor grade, lymphovascular invasion (LVI) and molecular subtypes, but not histopathologic type. In the multivariate analysis, the risk of additional non-SLNs metastasis correlated with the number of SLNs+, SLNs, non-SLNs and LVI.ConclusionOmiting ALND in patients with higher non-SLNs + rate outside the American College of Surgeons Oncology Group (ACSOG) Z0011 and the European Organization for Research and Treatment of Cancer (EORTC) 10,981–22023 AMAROS criteria should be considered with caution in clinical decision-making. To evaluate whether axillary radiotherapy and ALND provides equivalent regional control in breast cancer patients with obvious residual metastatic lymph nodes undesected in the axilla, a well-matched prospective randomized controlled trial is an urgent need.

Abstract Background Hyperuricaemia (HUA) poses a significant public health challenge on a global scale. It is mostly asymptomatic hyperuricemia (AHU) with unsatisfactory recognition and control rates. The role of health literacy in influencing health outcomes is of utmost importance, and enhancing health literacy is helpful for patients in managing risk factors. Additionally, social support and socioeconomic position (SEP) have been identified as potential factors influencing health. However, the exact relationships between these factors and AHU remain unclear. This study aimed to investigate the status of health literacy among patients with AHU and explore the relationships between health literacy, social support, SEP, and serum uric acid (SUA) levels. Methods A cross-sectional study was conducted among 349 participants with AHU in Luzhou, China. The research instruments included a sociodemographic characteristics questionnaire, the Health Literacy Scale for Chronic Patients (HLSCP), and the Social Support Scale (SSRS). The construction of the SEP index was achieved through the application of principal component analysis. Univariate and hierarchical regression analyses were used to evaluate the associations between SEP, social support, health literacy, and SUA levels. Furthermore, structural equation modelling (SEM) was utilized to examine these associations. Results (1) Most patients exhibited low health literacy (90.18 ± 15.11), and only 44.4% possessed basic health literacy. (2) SEP was positively correlated with SUA levels (β = 4.086, P

Abstract China, being a densely populated nation, faces a substantial economic burden due to a high incidence of lupus nephritis (LN) cases. The concealed onset of LN has resulted in many individuals have missed the optimal timing for treatment. The aim of the research is to study the serum metabolomics of Chinese LN patients using gas chromatography (GC)/mass spectrometry (MS) and liquid chromatography (LC)/MS to identify potential diagnostic markers. Fifty LN patients and fifty normal controls, matched for Body Mass Index (BMI) and age, were selected. Serum analysis was conducted using GC/MS and LC/MS, followed by multivariate statistical analysis. Various multidimensional analyses, including principal component analysis, partial least squares discrimination analysis, and orthogonal partial least squares discrimination analysis, along with one-dimensional analyses such as t-tests, were performed. Metabolites with variable importance in projection value > 1 and a p-value

The demand for food-grade β-mannanases, ideal for high-temperature baking, is increasing. Using the Komagataella phaffii (P. pastoris) expression system for β-mannanase production, this study aimed to enhance purification methods. We evaluated better conditions for production and purification of β-mannanase (PpRmMan134A) from recombinant P. pastoris X-33, focusing on a higher purity and reducing the production of endogenous secretory proteins in fermentation. By adjusting carbon and nitrogen sources, culture time, and temperature, we controlled cell growth to reduce the production of endogenous secretory proteins. The better-evaluated conditions involved culturing recombinant P. pastoris in 70 mL buffered glycerol complex medium for 24 h at 30 °C, then in modified buffered methanol-complex medium with 0.91% (w/v) methanol, 0.56% (w/v) sorbitol, and 0.48% (w/v) mannitol for another 24 h, which improved the PpRmMan134A yield and reduced endogenous secretory proteins, shortening the fermentation time by 72 h. An affordable purification method using ultrafiltration and salt-out precipitation was utilized. PpRmMan134A showed thermostability up to 100 °C and effectively degraded locust bean gum into smaller fragments, mainly producing mannotriose. In conclusion, with its enhanced purity due to reduced levels of endogenous secretory proteins, purified PpRmMan134A emerges as a promising enzyme for high-temperature baking applications.

Raindrops can scatter and absorb light, causing images to become blurry or distorted. To improve image quality by reducing the impact of raindrops, this paper proposes a novel generative adversarial network for image de-raining. The network comprises two parts: a generative network and an adversarial network. The generative network performs image de-raining. The adversarial network determines whether the input image is rain-free or de-rained. The generative network comprises two branches: the A branch, which follows a traditional convolutional network structure, and the U branch, which utilizes a U-Net architecture. The A branch includes a multi-scale module for extracting information at different scales and a residual attention module to reduce redundant information interference. The U branch contains an encoder module designed to address the loss of details and local information caused by conventional down-sampling. To improve the performance of the generative network in image de-raining, this paper employs a relative discriminator incorporating a mean squared error loss. This discriminator better measures the differences between rainy and rain-free images while effectively preventing the occurrence of gradient vanishing. Finally, this study performs visual and quantitative comparisons of the proposed method and existing methods on three established rain image datasets. In the quantitative experiments, the proposed method outperforms existing methods regarding PSNR, SSIM, and VIF metrics. Specifically, our method achieves an average PSNR, SSIM, and VIF of approximately 5%, 3%, and 4% higher than the MFAA-GAN method, respectively. These results indicate that the de-rained images generated via the proposed method are closer to rain-free images.

Abstract Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease (AD). It is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and the formation of Lewy bodies (LBs). Although PD is primarily considered a gray matter (GM) disease, alterations in white matter (WM) have gained increasing attention in PD research recently. Here we review evidence collected by magnetic resonance imaging (MRI) techniques which indicate WM abnormalities in PD, and discuss the correlations between WM changes and specific PD symptoms. Then we summarize transcriptome and genome studies showing the changes of oligodendrocyte (OLs)/myelin in PD. We conclude that WM abnormalities caused by the changes of myelin/OLs might be important for PD pathology, which could be potential targets for PD treatment.

This study combined emergy theory with water ecological footprint to analyze and evaluate the sustainable development status of water resources in Yunnan Province from 2012 to 2021. The water pollutant account and the water product account were supplemented to the water ecological footprint. The results showed that the water resources in Yunnan Province were generally in an ecological deficit during the study period, but their absolute values were very small. The ecological pressure index of water resources was high, while the sustainable utilization index of water resources was low, indicating that the water resources were in a state of unsustainable utilization. However, the emergy ecological footprint of water resources and the emergy ecological footprint of water resources of 10,000 Yuan GDP showed a decreasing trend, and the eco-economic coordination index of water resources was relatively high, indicating that the water resources will show a sustainable development trend in the future. The sustainable development of water resources was influenced by both natural ecological factors and social factors. Therefore, suggestions such as improving the utilization rate of water resources development, developing a green low-carbon economy, preventing and controlling water pollution, and protecting the water environment are conducive to promoting the sustainable development of water resources. HIGHLIGHTS Provided a new research method for the sustainable development of water resources in karst cities.; Supplemented the water pollutant account and the aquatic product account.; Calculated energy density and the average value of regional water resources.; Considering natural ecological and social factors, and proposing optimal paths.;

Karst rocky desertification refers to the process of land degradation caused by various factors such as climate change and human activities including deforestation and agriculture on a fragile karst substrate. Nutrient limitation is common in karst areas. Moss crust grows widely in karst areas. The microorganisms associated with bryophytes are vital to maintaining ecological functions, including climate regulation and nutrient circulation. The synergistic effect of moss crusts and microorganisms may hold great potential for restoring degraded karst ecosystems. However, our understanding of the responses of microbial communities, especially abundant and rare taxa, to nutrient limitations and acquisition in the presence of moss crusts is limited. Different moss habitats exhibit varying patterns of nutrient availability, which also affect microbial diversity and composition. Therefore, in this study, we investigated three habitats of mosses: autochthonal bryophytes under forest, lithophytic bryophytes under forest and on cliff rock. We measured soil physicochemical properties and enzymatic activities. We conducted high-throughput sequencing and analysis of soil microorganisms. Our finding revealed that autochthonal moss crusts under forest had higher nutrient availability and a higher proportion of copiotrophic microbial communities compared to lithophytic moss crusts under forest or on cliff rock. However, enzyme activities were lower in autochthonal moss crusts under forest. Additionally, rare taxa exhibited distinct structures in all three habitats. Analysis of co-occurrence network showed that rare taxa had a relatively high proportion in the main modules. Furthermore, we found that both abundant and rare taxa were primarily assembled by stochastic processes. Soil properties significantly affected the community assembly of the rare taxa, indirectly affecting microbial diversity and complexity and finally nutrient acquisition. These findings highlight the importance of rare taxa under moss crusts for nutrient acquisition. Addressing this knowledge gap is essential for guiding ongoing ecological restoration projects in karst rocky desertification regions.

An effective identification method for detecting illegal goods involving raw tobacco material is crucial for tobacco monopolies to conduct surveillance. We developed Nicotiana-specific molecular markers to determine whether seized goods contain raw tobacco material. The sequence data for genes related to the nicotine metabolism pathway and genomic data from the public Solanaceae database were used to establish Nicotiana-specific molecular markers. These markers were determined by experimentally verifying 17 types of nontobacco plant material and 91 types of tobacco material belonging to 11 sections of 3 subgenera. Two reliable Nicotiana-specific markers, Ntsp027 and Ntsp151, were selected from among the 209 newly developed markers. The results indicated that the primers corresponding to these two markers can amplify the target fragments in the 91 types of Nicotiana material without amplification of any PCR products in the 17 types of non-Nicotiana material. Furthermore, utilizing the marker Ntsp151, we verified the efficacy of the loop-mediated isothermal amplification (LAMP) assay in authenticating tobacco material. The identification of 21 tea-cigarette products via the combination of GC‒MS, a Nicotiana-specific molecular marker and LAMP methods underscores the utility of Nicotiana-specific DNA markers in determining whether illegal goods contain raw tobacco material. Our results indicate an impressive accuracy rate of 100%, which is consistent with the reliability assessment, underscoring the accuracy of these markers in effectively identifying tobacco material. Our findings can significantly augment the capacity for surveillance and anticounterfeiting efforts by aiding the fight against illicit trade and ensuring the integrity of all tobacco-related products in the market.

Local oxidative stress induced by surgical trauma has been recognized as one of pathogenesis for postsurgical adhesion tissue formation. Herein, tannic acid (TA) based metal-phenolic networks (MPNs) was assembled via chelating with Fe3+, and acted as a novel bio-filler for nanofibrous polycaprolactone (PCL) barrier membrane to endow it with reactive oxygen species (ROS) scavenging capacity. By chelating with Fe3+, the release of TA could last for more than 20 days, rendering the membrane with continuous ROS scavenging capacity. The modified membrane could effectively inhibit fibroblasts adhesion and proliferation, as well as immune cells recruitment, infiltration, and expression of pro-inflammatory cytokines. Consequently, a complete prevention of peritoneal adhesion formation was obtained in a rat model of sidewall defect-cecum abrasion, far better than commercial Poly lactic acid (PLA) membrane. Systematic biological mechanism investigations revealed that the enhanced anti-adhesion function was mainly ascribed to its robust ROS scavenging capacity, through which the PI3K-Akt signaling pathway was blocked, leading to repress of downstream NF-κB-TGFβ1-SMAD signaling pathway, finally inhibiting the bioactivity of fibroblasts and immune cells. This work provided a new strategy for the design of advanced barrier membrane, demonstrated its efficacy and mechanism on preventing postoperative adhesion, holding great promise for future clinical application.

Dermal white adipose tissue (dWAT) is a newly recognized layer of adipocytes within the reticular dermis of the skin. In many mammals, this layer is clearly separated by panniculus carnosus from subcutaneous adipose tissue (sWAT). While, they concentrated around the hair shaft and follicle, sebaceous gland, and arrector pili muscle, and forms a very specific cone geometry in human. Both the anatomy and the histology indicate that dWAT has distinct development and functions. Different from sWAT, the developmental origin of dWAT shares a common precursor with dermal fibroblasts during embryogenesis. Therefore, when skin injury happens and mature adipocytes in dWAT are exposed, they may undergo lipolysis and dedifferentiate into fibroblasts to participate in wound healing as embryogenetic stage. Studies using genetic strategies to selectively ablate dermal adipocytes observed delayed revascularization and re-epithelialization in wound healing. This review specifically summarizes the hypotheses of the functions of dWAT in wound healing. First, lipolysis of dermal adipocytes could contribute to wound healing by regulating inflammatory macrophage infiltration. Second, loss of dermal adipocytes occurs at the wound edge, and adipocyte-derived cells then become ECM-producing wound bed myofibroblasts during the proliferative phase of repair. Third, mature dermal adipocytes are rich resources for adipokines and cytokines and could release them in response to injury. In addition, the dedifferentiated dermal adipocytes are more sensitive to redifferentiation protocol and could undergo expansion in infected wound. We then briefly introduce the roles of dWAT in protecting the skin from environmental challenges: production of an antimicrobial peptide against infection. In the future, we believe there may be great potential for research in these areas: (1) taking advantage of the plasticity of dermal adipocytes and manipulating them in wound healing; (2) investigating the precise mechanism of dWAT expansion in infected wound healing.

Abstract With the continuous growth of the world's social economy and population, problems such as water shortage and water environment deterioration need to be solved urgently. Combining the emergy carrying capacity of water resources and the emergy ecological footprint method, the water security and sustainable development status of the typical city in the karst region (Anshun City) was evaluated, and the internal driving factors and optimization suggestions were discussed. The research results of water security in Anshun City show that: The water resources carrying capacity fluctuates greatly with rainfall and is generally in a low-level surplus state. The ecological pressure index and the sustainable utilization index show a downward trend. The pressure intensity of social and economic systems on water resources is increasing, and the sustainable development of water resources is not optimistic. Water resources security is mainly affected by natural ecological mechanisms centered on mountain systems, geological structures and hydrological systems, as well as social mechanisms centered on changes in population scale, land development and utilization, and urban development. In the future, the sustainable development of water resources can be promoted by changing the mode of economic development, optimizing the allocation of water resources, and protecting the ecological environment.

Abstract In this study, composite nanoparticles consisting of zein and hydroxypropyl beta-cyclodextrin were prepared using a combined antisolvent co-precipitation/electrostatic interaction method. The effects of calcium ion concentration on the stability of the composite nanoparticles containing both curcumin and quercetin were investigated. Moreover, the stability and bioactivity of the quercetin and curcumin were characterized before and after encapsulation. Fluorescence spectroscopy, Fourier Transform infrared spectroscopy, and X-ray diffraction analyses indicated that electrostatic interactions, hydrogen bonding, and hydrophobic interactions were the main driving forces for the formation of the composite nanoparticles. The addition of calcium ions promoted crosslinking of the proteins and affected the stability of the protein–cyclodextrin composite particles through electrostatic screening and binding effects. The addition of calcium ions to the composite particles improved the encapsulation efficiency, antioxidant activity, and stability of the curcumin and quercetin. However, there was an optimum calcium ion concentration (2.0 mM) that provided the best encapsulation and protective effects on the nutraceuticals. The calcium crosslinked composite particles were shown to maintain good stability under different pH and simulated gastrointestinal digestion conditions. These results suggest that zein–cyclodextrin composite nanoparticles may be useful plant-based colloidal delivery systems for hydrophobic bio-active agents.

Abstract Nisin is a natural bacteriocin that exhibits good antibacterial activity against Gram-positive bacteria. It has good solubility, stability, and activity under acidic conditions, but it becomes less soluble, stable, and active when the solution pH exceeds 6.0, which severely restricted the industrial application range of nisin as antibacterial agent. In this study, we investigated the potential of complexing nisin with a cyclodextrin carboxylate, succinic acid-β-cyclodextrin (SACD), to overcome the disadvantages. Strong hydrogen bonding was shown between the nisin and SACD, promoting the formation of nisin-SACD complexes. These complexes exhibited good solubility under neutral and alkaline conditions, and good stability after being held at high pH values during processing with high-steam sterilization. Moreover, the nisin-SACD complexes displayed significantly improved antibacterial activity against model Gram-positive bacteria (S. aureus). This study shows that complexation can improve the efficacy of nisin under neutral and alkaline situations, which may greatly broaden its application range in food, medical, and other industries.

Abstract Background The control measures of the coronavirus disease 2019 (COVID‐19) pandemic had influenced the activity of the influenza virus, and we were wondering the knowledge, attitudes, and practices (KAP) toward seasonal influenza vaccine among college students were having at the context of the COVID‐19 pandemic. Methods Online questionnaire survey of the college students was conducted and the data was collected anonymously, cross‐sectional study were used to describe the distribution of the KAP. Results There were 815 respondents in our study. Most participants have a high recognition of the effectiveness and safety of the influenza vaccine. However, a low awareness rate of influenza vaccine knowledge and vaccination rate (18%) against influenza was observed among college students. The education level and major would have a higher weight on the influence of KAP among the college students. Binary logistic regression analysis showed that the sex (OR = 2.163, p

In order to effectively solve the technical problem of the prediction of coal floor water inrush, according to the spatial distribution differences of geological conditions, combined with the typical coal mine, a partition calculation map of the development depth of the mineral pressure failure zone was made, and the mining process under different geological conditions has been numerically simulated and analyzed. And the empirical formula is modified by the numerical simulation calculation results, the calculation formula of the development depth of the mineral pressure failure zone of a typical coal mine was established, which effectively improves the accuracy of the calculation of the depth of the mineral pressure failure zone and lays the foundation for the quantification of evaluation indicators related to the aquifuge. According to the hydrogeological characteristics of southwest mines in China, 12 evaluation indicators determined from the three aspects of aquifer, aquifuge and geological structure, and an evaluation index system of water inrush risk of the karst aquifer in the coal floor has been constructed. On this basis, further using GIS technology and entropy weight theory, a multi-source information evaluation method for the risk of water inrush from coal floor was proposed, and verified the evaluation results.

In order to clarify the effects of different osmotic dehydration coupled with drying methods on the volatile substances of peach chips, head-space solid phase micro-extraction combined with gas chromatography mass spectrometry (HS-SPME-GC-MS) was used for the analysis of volatile components of peach chips prepared by sucrose osmotic dehydration combined with hot air drying (SH), isomalto-oligosaccharides osmotic dehydration combined with hot air drying (IH), sucrose osmotic dehydration combined with vacuum freeze drying (SF), isomalto-oligosaccharides osmotic dehydration combined with vacuum freeze drying (IF). The results showed that 61 volatile compounds were detected in the four drying methods, and the content of total volatile components in IF was the highest, which was 528.06 μg/g. Combined with the analysis of odor activity value (OAV), 13 (SH), 18 (IH), 20 (SF) and 22 (IF) key aroma components were selected respectively. Hexanal, trans-2-hexenal, nonanal, trans-2-nonenal, benzaldehyde, hexanol, trans-2-hexen-1-ol, 1-octen-3-oll, methyl benzoate and cis-3-hexenyl acetate were the key components in all drying methods. Principal component analysis of electronic nose could distinguish peach chips under different drying methods. The experiment showed that 30% isomalto-oligosaccharides osmotic dehydration combined with vacuum freeze-drying could obtain peach chips with good flavor. This study could provide a theoretical basis for the theoretical research and practical production of peach chips.

Abstract Background The Notch signaling mutation is associated with enhanced anti-tumor immune response in colorectal cancer (CRC). In this study, we aim to investigate the underlying mechanism and the predictive potential of Notch signaling mutation for responding to immunotherapy in CRC. Methods We analyzed the immune response associated genes in CRC with Notch signaling mutation concomitant with or without microsatellite instability (MSI) using TCGA dataset and investigated the mutation profiles of the Notch signaling pathway using cBioPortal. The Notch signaling scores and immune cell infiltration scores in different groups were calculated. We applied the Kaplan–Meier method for survival analysis in CRC patients who underwent immunotherapy, and the log-rank test to determine the statistically significant differences in survival. Notch1-knock-down cell line was constructed to detect the pathway and gene variations. Results We found that Notch signaling pathway mutation was associated with activated immune response, especially in those with MSI. Such association is useful for predicting a prolonged overall survival of CRC patients who underwent immune checkpoint inhibitor treatment. The mutation resulted in the functional loss of Notch signaling and may modulate the tumor immune microenvironment by increasing the expression of chemokines that are important for recruiting immune cells. Conclusions The Notch signaling mutation can modulate the chemotaxis of immune cells by upregulating the chemokine levels of the tumor immune microenvironment, and CRC patients with Notch signaling pathway mutation have better overall survival after immune checkpoint inhibitor treatment.

Oily sludge-derived activated carbon was prepared using the potassium hydroxide (KOH) activation method using oily sludge as a raw material, and one-factor experiments determined the best conditions for preparing activated carbon. The activated carbon’s morphological structure and surface chemical properties were analyzed by scanning different characterization tools, and the adsorption behavior of tetracycline hydrochloride was investigated. The results showed that the optimum conditions for preparing oily sludge-derived activated carbon were an activation temperature of 400 °C, activation time of 30 min, activator concentration of 1 mol/L, and impregnation ratio of 2 mL/g. After activation, the activated carbon had more pores and a more orderly crystal structure arrangement, the specific surface area was 2.07 times higher than that before activation, and the surface was rich in functional groups such as -HO, -C-O, -C=C, and -C-H, which increased the active sites of activated carbon. Physicochemical effects dominated the adsorption process. It belonged to the spontaneous heat absorption process under the quasi-secondary kinetic and Langmuir isothermal models. The maximum monolayer adsorption capacity of KOH-activated carbon was 205.1 mg·g−1.

Soybean whey contains high levels of off-flavors and anti-nutritional factors and is generally considered unsuitable for direct application in the food industry. In this work, to reduce beany off-flavors and anti-nutritional factors, and to improve its fermentation characteristics, soybean whey was treated with electrodialysis desalination, vacuum concentration and lactic acid bacteria (LAB) fermentation. The results showed that electrodialysis desalination increased the fermentation rate and the number of viable lactic acid bacteria of soybean whey yogurt. More than 90% of the antinutritional factor level (urease and trypsin inhibitory activity) was removed due to high-temperature denaturation inactivation and LAB degradation. Concentrated desalted soybean whey yogurt (CDSWY) possessed larger values for firmness and consistency, and a denser network microstructure compared with undesalted yogurt. Over 90% of off-flavors including hexanal, 1-octen-3-ol and 1-octen-3-one were removed after electrodialysis desalination and concentration treatment. Meanwhile, the newly generated β-damascenone through carotenoid degradation and 2,3-butanedione improved the pleasant flavor and sensory quality of CDSWY, while the salty taste of CSWY lowered its sensory quality. This study provided a theoretical basis for better utilization of soybean whey to develop a plant-based yogurt like dairy yogurt.

Abstract Background Finding correlation patterns is an important goal of analyzing biological data. Currently available methods for correlation analysis mainly use non-direct associations, such as the Pearson correlation coefficient, and focus on the interpretation of networks at the level of modules. For biological objects such as genes, their collective function depends on pairwise gene-to-gene interactions. However, a large amount of redundant results from module level methods often necessitate further detailed analysis of gene interactions. New approaches of measuring direct associations among variables, such as the part mutual information (PMI), may help us better interpret the correlation pattern of biological data at the level of variable pairs. Results We use PMI to calculate gene co-expression networks of cancer mRNA transcriptome data. Our results show that the PMI-based networks with fewer edges could represent the correlation pattern and are robust across biological conditions. The PMI-based networks recall significantly more important parts of omics defined gene-pair relationships than the Pearson Correlation Coefficient (PCC)-based networks. Based on the scores derived from PMI-recalled copy number variation or DNA methylation gene-pairs, the patients with cancer can be divided into groups with significant differences on disease specific survival. Conclusions PMI, measuring direct associations between variables, extracts more important biological relationships at the level of gene pairs than conventional indirect association measures do. It can be used to refine module level results from other correlation methods. Particularly, PMI is beneficial to analysis of biological data of the complicated systems, for example, cancer transcriptome data.

Base editing tools enabled efficient conversion of C:G or A:T base pairs to T:A or G:C, which are especially powerful for targeting monogenic lesions. However, in vivo correction of disease-causing mutations is still less efficient because of the large size of base editors. Here, we designed a dual adeno-associated virus (AAV) strategy for in vivo delivery of base editors, in which deaminases were linked to Cas9 through the interaction of GCN4 peptide and its single chain variable fragment (scFv) antibody. We found that one or two copies of GCN4 peptide were enough for the assembly of base editors and produced robust targeted editing. By optimization of single-guide RNAs (sgRNAs) that target phenylketonuria (PKU) mutation, we were able to achieve up to 27.7% correction in vitro. In vivo delivery of this dual AAV base editing system resulted in efficient correction of PKU-related mutation in neonatal mice and subsequent rescue of hyperphenylalaninemia-associated syndromes. Considering the similarity between Cas9 proteins from different organisms, our delivery strategy will be compatible with other Cas9-derived base editors.

Abstract Background Cell-free therapy has been inspired as a promising approach to overcome the limitations of traditional stem cell therapy. However, the therapeutic effect between extracellular vesicles and conditioned medium with the same source had not been compared. Our previous studies have shown that both the conditioned medium of adipose tissue (adipose tissue extract, ATE) and its further purification product small extracellular vesicles (sEV-AT) contributed to adipose tissue regeneration. In this study, we aimed to compare the ATE and sEV-AT in composition, inductivity on cells and de novo adipose regenerative potential. Methods The characteristics of sEV-AT and ATE were compared through protein and particle yield, particle size distribution and composition. The inductivity of sEV-AT and ATE on cells were compared through co-culture of sEV-AT or ATE with ASC, HUVEC and RAW264.7 in vitro. The capacity of promoting de novo adipogenesis was compared by implanting the silicone tube containing sEV-AT or ATE subcutaneously in vivo. Results More particles and concentrated particle size distribution were detected in sEV-AT. In turn, more soluble factors and multiple peaks in particle size distribution were detected in ATE. In 1662 common proteins of sEV-AT and ATE, there were 984 (59.2%) proteins enriched twice more in sEV-AT than in ATE. With the prerequisite of equivalent protein concentration, sEV-AT outperformed ATE in promoting proliferation, migration and regeneration potential of cells those contributing adipose tissue regeneration in vitro. Furthermore, sEV-AT expedited the de novo adipose tissue regeneration and angiogenesis at the early stage than ATE in vivo, but sEV-AT and ATE group formed similar neoadipose tissue and new vessels at week 12. Conclusions Our results provided a direct comparison between EV and conditioned medium as cell-free therapeutic strategy. Both sEV and ATE had specific biological signature to facilitate tissue repair. Considering the convenience of extraction and acceptable effect, ATE represented a feasible product of cell-free therapy, providing another option for different situations in clinical application. Furthermore, the complex contents of both sEV-AT and ATE should be studied comprehensively to avoid possible negative effects and to ensure sufficient safety for clinical applications.

Abstract Background tRNA-derived fragments (tRFs) have been shown to have critical regulatory roles in cancer biology. However, the contributions of tRFs to colorectal cancer (CRC) remain largely unknown. Methods tRF3008A (a tRFRNA derived from tRNAVal) was identified by RNA sequencing and validated by quantitative reverse transcription PCR. The role of tRF3008A in CRC progression was assessed both in vitro and in vivo, and its downstream target genes were identified and validated in CRC cells. RNA pull-down with mass spectrometry and AGO-RIP were used to confirm the interaction of tRF3008A and AGO proteins. The clinical implications of tRF3008A were assessed in CRC tissues and blood samples. Results The expression of tRF3008A was reduced in colorectal cancer, and its reduction was significantly correlated with advanced and metastatic disease in CRC. Patients with low tRF3008A expression showed significantly shorter DFS, and multivariate analysis identified tRF3008A as an independent prognostic biomarker in CRC. Functionally, tRF3008A inhibits the proliferation and migration of CRC in vivo and in vitro by repressing endogenous FOXK1, a positive regulator of the Wnt/β-catenin pathway. Mechanistically, tRF3008A binds to AGO proteins as a guide to destabilize oncogenic FOXK1 transcript. Conclusions tRF3008A suppresses the metastasis and progression of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner.

The emulsion gels that can be used as solid fat replacers were produced with different polysaccharides (κ-carrageenan, κC; high-acyl gellan, HA; konjac glucomannanon, and KGM), pea protein isolate (PPI) and sunflower seed oil. The effect of polysaccharide concentration on the texture, rheological property, microstructure, and water holding capacity of the mixed emulsion gels were investigated. Rheological results showed that the presence of polysaccharides enhanced the hardness, storage modulus and resistance against deformation of emulsion gel, where PPI/κC system exhibited superior hardness with a similar level of pig back fat, due to the self-gelation behavior of κC. CLSM and SEM results showed that the presence of κC, HA, and KGM broke the uniform structure of gel network and formed irregular, threadlike, and oval shaped inclusions respectively, resulting in the broken and coalescence of oil droplets. The α-helix content of emulsion gels decreased, while β-sheet, β-turn and random coils slightly increased due to the unfolding of protein during gel formation. This study may offer a valuable strategy for the development of solid fat mimetic with the characteristics closing to the pig back fat.

Abstract Background The role of postoperative radiotherapy (PORT) in cardiovascular-pulmonary disease mortality in patients with stage IIIA-N2 resected non-small cell lung cancer (NSCLC) remains uncertain. The purpose of this population-based analysis was to explore the effect of PORT on cardiovascular-pulmonary disease mortality in these patients. Methods Patients aged ≥ 18 years with stage IIIA-N2 resected NSCLC were identified in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 and were grouped according to the use of PORT. Propensity score matching (PSM) was used to account for differences in baseline characteristics between the Non-PORT and PORT groups. The cumulative risk for cardiovascular-pulmonary disease death was estimated using the cumulative incidence curve. Competing risk regression was used to run univariate and multivariate analyses to evaluate risk factors. Results A total of 3981 patients were included in the study population. Among them, 1446 patients received PORT, and 2535 did not. A total of 1380 patients remained in each group after PSM, and the baseline characteristics were not significantly different between the two groups. The cumulative incidence of cardiovascular-pulmonary mortality was 10.93% in the Non-PORT group compared with 9.85% in the PORT group. There was no significant difference in the cumulative risk between the two groups (HR 1.07, 95% CI 0.77–1.48, p = 0.703). Multivariate analysis indicated that PORT had no significant impact on increased risk, with an HR of 1.18 (p = 0.377). Conclusions No significant differences between the PORT and Non-PORT groups were found in cardiovascular-pulmonary-specific modalities in this study. Further studies are required to validate these results. This study highlights the importance of long-term surveillance for NSCLC patients.

Background: Tumor-derived lactate can modulate the function of infiltrating immune cells to establish an immunosuppressive microenvironment that favors tumor progression. However, possible effects of lactate-related genes (LRGs) on the tumor microenvironment (TME) of breast cancer (BRCA) are still unknown.Methods: LRGs were comprehensively screened from lactate metabolism-related pathways. We correlated the expression of these LRGs with immune cell infiltrating characteristics in the TME and clinicopathological features of patients. We also established a lactate score for quantifying lactate metabolism patterns of cancers and to predict of recurrence-free survival (RFS).Results: We successfully constructed a lactate score that was an independent prognostic factor in BRCA. A low lactate score, which was associated with immune activation with increased CD8+ T cells infiltration levels, indicated an inflamed TME. Consistently, higher expression levels of inhibitory immune checkpoints, including PD-L1, LAG3, CTLA4, and TIM3, as observed from high lactate score subgroup, suggested an immune-desert phenotype as well as poor prognosis. Moreover, a low lactate score predicted the increased chemotherapeutic drug sensitivity and enhanced anti-PD-1 immunotherapy responses.Conclusion: The present study analyzed the potential roles of LRGs in the TME diversity and prognosis. These results will help to improve our understanding of the characteristics of TME immune cell infiltration and guide the development of more effective immunotherapy strategies.

Phenylketonuria (PKU) is an inherited metabolic disorder caused by mutation within phenylalanine hydroxylase (PAH) gene. Loss-of-function of PAH leads to accumulation of phenylalanine in the blood/body of an untreated patient, which damages the developing brain, causing severe mental retardation. Current gene therapy strategies based on adeno-associated vector (AAV) delivery of PAH gene were effective in male animals but had little long-term effects on blood hyperphenylalaninemia in females. Here, we designed a gene therapy strategy using AAV to deliver a human codon-optimized phenylalanine amino lyase in a liver-specific manner. It was shown that PAL was active in lysing phenylalanine when it was expressed in mammalian cells. We produced a recombinant adeno-associated vector serotype 8 (AAV8) viral vector expressing the humanized PAL under the control of human antitrypsin (hAAT) promoter (AAV8-PAL). A single intravenous administration of AAV8-PAL caused long-term correction of hyperphenylalaninemia in both male and female PKU mice (strain Pahenu2). Besides, no obvious liver injury was observed throughout the treatment process. Thus, our results established that AAV-mediated liver delivery of PAL gene is a promising strategy in the treatment of PKU.

Chromobox (CBX) family members are vital epigenetic regulators that repress the transcription of target genes through chromatin modification. Several studies have investigated the role of CBX family members in cancer. However, the function and prognostic value of diverse CBX family members in non‐small‐cell lung cancer remain largely unknown. In this study, we reveal that CBX family members are overexpressed in non‐small‐cell lung cancer tissue compared with normal lung tissue, with the exception of CBX6. Kaplan–Meier analysis demonstrated that high expressions of CBX1 and CBX3 are correlated with overall survival, disease‐specific survival, disease‐free interval, and progression‐free interval for patients with lung adenocarcinoma (LUAD). Furthermore, regression model analysis suggests that CBX3 may be suitable as an independent prediction factor for overall survival and progression‐free interval in patients with LUAD. In addition, CBX3 mRNA expression was found to be associated with tumor diameter and lymph node metastasis. Gene enrichment analysis suggests that CBX3 is involved in the cell cycle and P53 signaling pathways. Aberrant expression of CBX3 in LUAD is correlated with DNA copy number alteration. In summary, our data imply that CBX3 plays an important role in the promotion of LUAD and may thus have potential as a prognostic biomarker and molecular therapeutic target for the disease.

Abstract We present a base editing system, in which base editors are attached to different sites of sgRNA scaffold (sgBE). Each independent sgBE has its own specific editing pattern for a given target site. Among tested sgBEs, sgBE-SL4, in which deaminase is attached to the last stem-loop of sgRNA, yields the highest editing efficiency in the window several nucleotides next to the one edited by BE3. sgBE enables the simultaneous editing of adenine and cytosine. Finally, in order to facilitate in vivo base editing, we extend our sgBE system to an AAV-compatible Cas9, SaCas9 (Staphylococcus aureus), and observe robust base editing.

The opinion recognition for comments in Internet media is a new task in text analysis. It takes comment statements as the research object, by learning the opinion tendency in the original text with annotation, and then performing opinion tendency recognition on the unannotated statements. However, due to the uncertainty of NLP (natural language processing) in short scenes and the complexity of Chinese text, existing methods have some limitations in accuracy and application scenarios. In this paper, we propose an opinion tendency recognition model HGAT (heterogeneous graph attention network) that integrates text vector and context structure methods to address the above problems. This method first trains a text vectorization model based on annotation text content, then constructs an isomorphic graph with annotation, news, and theme as its apex, and then optimizes the feature vectors of all nodes using an isomorphic graph neural network model with attention mechanism. In addition, this article collected 1,684,318 news items and 57,845,091 comments based on Toutiao, sifted through 511 of those stories and their corresponding 103,787 comments, and tested the impact of HGAT on this dataset. Experiments show that this method has stable improvement effect on different NLP methods, increasing accuracy by 2–10%, and provides a new perspective for opinion tendency recognition.

Hypophosphatasia (HPP) is a rare inherited disorder characterized by defective bone mineralization and is highly variable in its clinical phenotype. The disease occurs due to various loss-of-function mutations in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). In this work, a data-driven and biophysics-based approach is proposed for the large-scale analysis of ALPL mutations-from nonpathogenic to severe HPPs. By using a pipeline of synergistic approaches including sequence-structure analysis, network modeling, elastic network models and atomistic simulations, we characterized allosteric signatures and effects of the ALPL mutations on protein dynamics and function. Statistical analysis of molecular features computed for the ALPL mutations showed a significant difference between the control, mild and severe HPP phenotypes. Molecular dynamics simulations coupled with protein structure network analysis were employed to analyze the effect of single-residue variation on conformational dynamics of TNSALP dimers, and the developed machine learning model suggested that the topological network parameters could serve as a robust indicator of severe mutations. The results indicated that the severity of disease-associated mutations is often linked with mutation-induced modulation of allosteric communications in the protein. This study suggested that ALPL mutations associated with mild and more severe HPPs can exert markedly distinct effects on the protein stability and long-range network communications. By linking the disease phenotypes with dynamic and allosteric molecular signatures, the proposed integrative computational approach enabled to characterize and quantify the allosteric effects of ALPL mutations and role of allostery in the pathogenesis of HPPs.

Cancer stem-like cells (CSLCs) acquire enhanced immune checkpoint responses to evade immune cell killing and promote tumor progression. Here we showed that signal regulatory protein γ (SIRPγ) determined CSLC properties and immune evasiveness in a small population of lung adenocarcinoma (LUAD) cancer cells. A SIRPγhi population displayed CSLC properties and transmitted the immune escape signal through sustaining CD47 expression in both SIRPγhi and SIRPγlo/– tumor cells. SIRPγ bridged MST1 and PP2A to facilitate MST1 dephosphorylation, resulting in Hippo/YAP activation and leading to cytokine release by CSLCs, which stimulated CD47 expression in LUAD cells and consequently inhibited tumor cell phagocytosis. SIRPγ promoted tumor growth and metastasis in vivo through YAP signaling. Notably, SIRPγ targeting with genetic SIRPγ knockdown or a SIRPγ-neutralizing antibody inhibited CSLC phenotypes and elicited phagocytosis that suppressed tumor growth in vivo. SIRPG was upregulated in human LUAD and its overexpression predicted poor survival outcome. Thus, SIRPγhi cells serve as CSLCs and tumor immune checkpoint–initiating cells, propagating the immune escape signal to the entire cancer cell population. Our study identifies Hippo/YAP signaling as the first mechanism by which SIRPγ is engaged and reveals that targeting SIRPγ represents an immune- and CSLC-targeting strategy for lung cancer therapy.

Sepsis represents a syndrome of systemic inflammatory response, which is mostly a result of infection with various pathogenic microorganisms, characterized by an uncontrolled infection response of the organism leading to life-threatening organ dysfunction. Long noncoding RNA (lncRNA), as competing endogenous RNA, can affect the binding of microRNA (miRNA) to mRNA, thus influencing the development of sepsis. In this study, based on transcriptome data from GEO database, we screened differentially expressed lncRNAs and constructed lncRNA-miRNA-mRNA network. And pathway IL-17RA-1/miR-7847-3p/protein kinase C gamma (PRKCG) coexpression network was successfully sorted out. The effect of this network on LPS-induced sepsis model in THP-1 cells was also verified by CCK-8, scratch, ELISA, Western blot, and qRT-PCR assays. Corresponding binding sites of miR-7847-3p to IL-17RA-1 and miR-7847-3p to PRKCG were verified using dual luciferase gene reporter assays, respectively. Compared with control, si-IL-17RA-1 significantly inhibited the cell viability and migration ability of THP-1, and levels of proinflammatory factors IL-6, IL-1β, and TNF-α secreted were markedly decreased, and the expression of IL-17RA-1, PRKCG, p-MEKK1, and p-JNK were markedly reduced. In addition, IL-17RA-1 could target binding to miR-7847-3p and inhibit its expression, and miR-7847-3p could also bind to PRKCG. Our experiments demonstrate that IL17-RA-1 attenuates the sepsis response through the miR-7847-3p/MAPK pathway, and this competing endogenous RNA (ceRNA) network may be a potential approach to predict and combat sepsis.

Hypoxia is a characteristic of tumor microenvironment (TME) and is a major contributor to tumor progression. Yet, subtype identification of tumor-associated non-malignant cells at single-cell resolution and how they influence cancer progression under hypoxia TME remain largely unexplored. Here, we used RNA-seq data of 424,194 single cells from 108 patients to identify the subtypes of cancer cells, stromal cells, and immune cells; to evaluate their hypoxia score; and also to uncover potential interaction signals between these cells in vivo across six cancer types. We identified SPP1+ tumor-associated macrophage (TAM) subpopulation potentially enhanced epithelial–mesenchymal transition (EMT) by interaction with cancer cells through paracrine pattern. We prioritized SPP1 as a TAM-secreted factor to act on cancer cells and found a significant enhanced migration phenotype and invasion ability in A549 lung cancer cells induced by recombinant protein SPP1. Besides, prognostic analysis indicated that a higher expression of SPP1 was found to be related to worse clinical outcome in six cancer types. SPP1 expression was higher in hypoxia-high macrophages based on single-cell data, which was further validated by an in vitro experiment that SPP1 was upregulated in macrophages under hypoxia-cultured compared with normoxic conditions. Additionally, a differential analysis demonstrated that hypoxia potentially influences extracellular matrix remodeling, glycolysis, and interleukin-10 signal activation in various cancer types. Our work illuminates the clearer underlying mechanism in the intricate interaction between different cell subtypes within hypoxia TME and proposes the guidelines for the development of therapeutic targets specifically for patients with high proportion of SPP1+ TAMs in hypoxic lesions.

DNA methyltransferase 1 (DNMT1), a large multidomain enzyme, is believed to be involved in the passive transmission of genomic methylation patterns via methylation maintenance. Yet, the molecular mechanism of interaction networks underlying DNMT1 structures, dynamics, and its biological significance has yet to be fully characterized. In this work, we used an integrated computational strategy that combined coarse-grained and atomistic simulations with coevolution information and network modeling of the residue interactions for the systematic investigation of allosteric dynamics in DNMT1. The elastic network modeling has proposed that the high plasticity of RFTS has strengthened the correlated behaviors of DNMT1 structures through the hinge sites located at the RFTS-CD interface, which mediate the collective motions between domains. The perturbation response scanning (PRS) analysis combined with the enrichment analysis of disease mutations have further highlighted the allosteric potential of the RFTS domain. Furthermore, the long-range paths connect the intra-domain interactions through the TRD interface and catalytic interface, emphasizing some key inter-domain interactions as the bridges in the global allosteric regulation of DNMT1. The observed interplay between conserved intra-domain networks and dynamical plasticity encoded by inter-domain interactions provides insights into the intrinsic dynamics and functional evolution, as well as the design of allosteric modulators of DNMT1 based on the TRD interface.

Background Annexin 1 (ANXA1) expression is associated with the malignant tumor phenotype, making it an attractive therapeutic target. However, little is known about the regulation of ANXA1 in non‐small cell lung cancer (NSCLC). Methods We investigated the biological roles of ANXA1 in tumor growth, migration, and invasion, and explored the possibility of ANXA1 as a potential therapeutic target for the treatment of NSCLC. Results Our findings revealed that ANXA1 enhanced nuclear factor (NF)‐κB activation in NSCLC cells by interaction with inhibitor of NF‐κB kinase complex subunit, IKKγ. We also found that NF‐κB could negatively regulate microRNA (miR)‐26a, and miR‐26a was regulated through the ANXA1–NF‐κB regulatory pathway. NF‐κB activation negatively regulated by miR‐26a was confirmed in NSCLC. Conclusion Together, these results provide evidence of the mechanisms of the ANXA1–NF‐κB–miR‐26a regulatory pathway in the invasion and migration in NSCLC.

In this work, pea albumins (PAs) were efficiently recovered by complexation with dextran sulfate (DS), and the emulsifying ability and stability of PA/DS complexes were studied. The largest amounts of PAs (81.25%) were recovered at r = 5:1 and pHmax (pH 3.41) by forming insoluble complexes; and only soluble complexes were formed at r = 2:1 and over the whole pH range (2.0–7.0). The emulsions stabilized by PA/DS soluble complexes remained stable under acidic conditions due to the highly negatively charge (from −45.10 ± 0.40 to −57.23 ± 0.66 mV) and small particle size (0.168 ± 0.010–0.448 ± 0.004 μm), while emulsions stabilized by PAs alone generated a strong creaming and serum separation at pH 5 and 6. In terms of emulsifying stability, all PA emulsions and unheated PA/DS emulsions became unstable with different creaming index after 14 days storage. SDS-PAGE results showed that the interface adsorption proteins of unheated emulsions mainly consisted of PA1a, which was unfavorable to the stability of the interface. On the contrary, heat treatment (95 °C, 30 min) and complexation (PA/DS = 2:1) enhanced the adsorption of PA2 and lectin at the interface, inhibiting the aggregation of PA2 and lectin. This resulted in long-term stability of the PA/DS emulsions under acidic conditions.

Regulatory B cells (Breg) are considered as immunosuppressive cells. Different subsets of Breg cells have been identified both in human beings and in mice. However, there is a lack of unique markers to identify Breg cells, and the heterogeneity of Breg cells in different organs needs to be further illuminated. In this study, we performed high-throughput single-cell RNA sequencing (scRNA-seq) and single-cell B-cell receptor sequencing (scBCR-seq) of B cells from the murine spleen, liver, mesenteric lymph nodes, bone marrow, and peritoneal cavity to better define the phenotype of these cells. Breg cells were identified based on the expression of immunosuppressive genes and IL-10-producing B (B10) cell-related genes, to define B10 and non-B10 subsets in Breg cells based on the score of the B10 gene signatures. Moreover, we characterized 19 common genes significantly expressed in Breg cells, including Fcrl5, Zbtb20, Ccdc28b, Cd9, and Ptpn22, and further analyzed the transcription factor activity in defined Breg cells. Last, a BCR analysis was used to determine the clonally expanded clusters and the relationship of Breg cells across different organs. We demonstrated that Atf3 may potentially modulate the function of Breg cells as a transcription factor and that seven organ-specific subsets of Breg cells are found. Depending on gene expression and functional modules, non-B10 Breg cells exhibited activated the TGF-β pathway, thus suggesting that non-B10 Breg cells have specific immunosuppressive properties different from conventional B10 cells. In conclusion, our work provides new insights into Breg cells and illustrates their transcriptional profiles and BCR repertoire in different organs under physiological conditions.

ObjectiveThe mesentery is a potential site of residual tumor in patients with colorectal cancer (CRC). However, the mesenteric immune microenvironment remains unclear. In this study, we investigated the immune landscape of the mesentery, particularly the role of lymphocytes and its association with the clinicopathological characteristics of CRC.MethodsFlow cytometry was used to detect lymphocytes in the paired mesenteric tissue specimens adjacent to the colorectal tumors and normal mesenteric tissue specimens 10 cm away from the colorectal tumor edge and preoperative peripheral blood samples obtained from patients with CRC who underwent surgery. T-distributed stochastic neighbor embedding was utilized to analyze multiparameter flow cytometry data. Multiplex immunohistochemistry was performed to evaluate T cells subsets in the paired mesentery adjacent to the colorectal tumors and normal mesentery. The Fisher’s exact test and non-parametric Wilcoxon’s matched-pairs tests were used for statistical analysis. The non-parametric Mann-Whitney U test was used to determine associations between percentage data and clinical parameters of patients with CRC.ResultsWe found that immune cells in the normal mesentery were mainly of lymphoid lineage. Compared with peripheral blood, the normal mesentery showed decreased NK cells and the CD4/CD8 ratio and increased CD3+ CD56+, memory CD4+ T, memory CD8+ T, CD4+ tissue-resident memory T (TRM), and CD8+ TRM cells. Compared with the normal mesentery, the mesentery adjacent to the colorectal tumor showed increased B and regulatory T cells and decreased NK, CD3+ CD56+, CD4+ TRM, and CD8+ TRM cells. Moreover, memory CD8+ T cells and plasmablasts are negatively correlated with the depth of invasion of CRC. Increased memory CD4+ T cells are associated with distant metastasis of CRC and high preoperative serum carcinoembryonic antigen levels.ConclusionThe mesentery shows a specific immune microenvironment, which differs from that observed in peripheral blood. CRC can alter the mesenteric immune response to promote tumor progression.

Rectal cancer (RC) is the leading cause of tumor-related death among both men and women. The efficacy of immunotherapy for rectal cancer is closely related to the immune infiltration level. The N6-methyladenosine (m6A) modification may play a pivotal role in tumor-immune interactions. However, the roles of m6A-related genes in tumor-immune interactions of rectal cancer remain largely unknown. After an evaluation on the expression levels of m6A-related genes and their correlations with the prognosis of rectal cancer patients, we found that METTL14 was the only gene to be significantly correlated with prognosis in rectal cancer patients. Therefore, we further observed the impact of METTL14 expression and m6A modification on the immune infiltration in rectal cancer. Our study indicates that low expression of the m6A “writer” gene METTL14 in rectal cancer may lead to the downregulation of m6A RNA modification, thus reducing the level of immune cell infiltration and resulting in poor prognosis. METTL14 expression level is an independent prognostic factor in rectal cancer and is positively correlated with the immune infiltration level. Our study identified METTL14 as a potential target for enhancing immunotherapy efficacy in rectal cancer.

In this work, rutin (RT)–loaded zein–carboxymethyl starch (CMS) nanoparticles were successfully prepared by the antisolvent precipitation method. The effect of CMS on composite nanoparticles at different concentrations was studied. When the ratio of zein–RT–CMS was 10:1:30, the encapsulation efficiency (EE) was the highest, reaching 73.5%. At this ratio, the size of the composite nanoparticles was 196.47 nm, and the PDI was 0.13, showing excellent dispersibility. The results of fluorescence spectroscopy, FTIR, XRD, and CD showed that electrostatic interaction, hydrogen bonding, and hydrophobic interaction were the main driving forces for the formation of nanoparticles. It can be seen from the FE–SEM images that the zein–RT–CMS nanoparticles were spherical. With the increase in the CMS concentration, the particles gradually embedded in the cross–linked network of CMS (10:1:50). After RT was loaded on zein–CMS nanoparticles, the thermal stability and pH stability of RT were improved. The results showed that zein–CMS was an excellent encapsulation material for bioactive substances.

Plant polyphenols have attracted considerable attention because of their key roles in preventing many diseases, including high blood sugar, high cholesterol, and cancer. A variety of functional foods have been designed and developed with plant polyphenols as the main active ingredients. Polyphenols mainly come from vegetables and fruits and can generally be divided according to their structure into flavonoids, astragalus, phenolic acids, and lignans. Polyphenols are a group of plant-derived functional food ingredients with different molecular structures and various biological activities including antioxidant, anti-inflammatory, and anticancer properties. However, many polyphenolic compounds have low oral bioavailability, which limits the application of polyphenols in nutraceuticals. Fortunately, green bio-based nanocarriers are well suited for encapsulating, protecting, and delivering polyphenols, thereby improving their bioavailability. In this paper, the health benefits of plant polyphenols in the prevention of various diseases are summarized, with a review of the research progress into bio-based nanocarriers for the improvement of the oral bioavailability of polyphenols. Polyphenols have great potential for application as key formulations in health and nutrition products. In the future, the development of food-grade delivery carriers for the encapsulation and delivery of polyphenolic compounds could well solve the limitations of poor water solubility and low bioavailability of polyphenols for practical applications.

As a renewable resource, the market trend of plant protein has increased significantly in recent years. Compared with animal protein, plant protein production has strong sustainability factors and a lower environmental impact. Many bioactive substances have poor stability, and poor absorption effects limit their application in food. Plant protein-based carriers could improve the water solubility, stability, and bioavailability of bioactive substances by different types of delivery systems. In this review, we present a detailed and concise summary of the effects and advantages of various plant protein-based carriers in the encapsulation, protection, and delivery of bioactive substances. Furthermore, the research progress of food-grade bioactive ingredient delivery systems based on plant protein preparation in recent years is summarized, and some current challenges and future research priorities are highlighted. There are some key findings and conclusions: (i) plant proteins have numerous functions: as carriers for transportation systems, a shell or core of a system, or food ingredients; (ii) plant protein-based carriers could improve the water solubility, stability, and bioavailability of bioactive substances by different types of delivery systems; and (iii) plant protein-based carriers stabilize bioactive substances with potential applications in the food and nutrition fields.

Patients suffering from zygomatic complex fractures always present facial deformity and dysfunctions, and thereafter develop psychological and physiological problems. It is really hard to get an ideal prognosis for the zygomatic complex fractures because of the complicated anatomical structures. Computer-assisted surgery techniques, as the new emerging auxiliary methods, can optimize the surgical protocol, predict operation outcomes, and improve the accuracy and quality of the operation. Meanwhile the postoperative complications can be reduced effectively. This review aims to provide a comprehensive overview of the application of computer-assisted surgery techniques in the management of zygomatic complex fractures. Keywords: Zygomatic complex fractures, Computer-assisted surgical techniques, Accuracy, Reduction