Search

Abstract The fusion of viruses with cellular membranes is a critical step in the life cycle of enveloped viruses. This process is facilitated by viral fusion proteins, many of which are conformationally pH-sensitive. The specifics of how changes in pH initiate this fusion have remained largely elusive. This study presents the cryo-electron microscopy (cryo-EM) structures of a prototype class III fusion protein, GP64, in its prefusion and early intermediate states, revealing the structural intermediates accompanying the membrane fusion process. The structures identify the involvement of a pH-sensitive switch, comprising H23, H245, and H304, in sensing the low pH that triggers the initial step of membrane fusion. The pH sensing role of this switch is corroborated by assays of cell-cell syncytium formation and dual dye-labeling. The findings demonstrate that coordination between multiple histidine residues acts as a pH sensor and activator. The involvement of a multi-histidine switch in viral fusion is applicable to fusogens of human-infecting thogotoviruses and other viruses, which could lead to strategies for developing anti-viral therapies and vaccines.

Abstract miRNA has emerged as a crucial regulator in various of pathological and physiological processes, yet its precise mechanism of action the detailed mechanism of their action in Head and neck squamous cell carcinoma (HNSCC) remains incompletely understood. This study sheds light on the role of mi-151-5p, revealing its significantly elevated expression in tumor cells, which notably enhances the invasion and migration of HNSCC cells. This effect is achieved through directly targeting LY6/PLAUR Domain Containing 3 (LYPD3) by miR-151-5p, involving complementary binding to the 3’-untranslated regions (3’-UTR) in the mRNA of LYPD3. Consequently, this interaction accelerates the metastasis of HNSCC. Notably, clinical observations indicate a correlation between high expression of miR-151-5p and low levels of LYPD3 in clinical settings are correlated with poor prognosis of HNSCC patients. Furthermore, our investigation demonstrates that glycosylation of LYPD3 modulates its subcellular localization and reinforces its role in suppressing HNSCC metastasis. Additionally, we uncover a potential regulatory mechanism involving the facilitation of miR-151-5p maturation and accumulation through N6-methyladenosine (m6A) modification. This process is orchestrated by methyltransferase-like 3 (METTL3) and mediated by a newly identified reader, heterogeneous nuclear ribonucleoprotein U (hnRNP U). These findings collectively underscore the significance of the METTL3/miR-151-5p/LYPD3 axis serves as a prominent driver in the malignant progression of HNSCC.

Summary: Patients with diabetes often experience fragile fractures despite normal or higher bone mineral density (BMD), a phenomenon termed the diabetic bone paradox (DBP). The pathogenesis and therapeutics opinions for diabetic bone disease (DBD) are not fully explored. In this study, we utilize two preclinical diabetic models, the leptin receptor-deficient db/db mice (DB) mouse model and the streptozotocin-induced diabetes (STZ) mouse model. These models demonstrate higher BMD and lower mechanical strength, mirroring clinical observations in diabetic patients. Advanced glycation end products (AGEs) accumulate in diabetic bones, causing higher non-enzymatic crosslinking within collagen fibrils. This inhibits intrafibrillar mineralization and leads to disordered mineral deposition on collagen fibrils, ultimately reducing bone strength. Guanidines, inhibiting AGE formation, significantly improve the microstructure and biomechanical strength of diabetic bone and enhance bone fracture healing. Therefore, targeting AGEs may offer a strategy to regulate bone mineralization and microstructure, potentially preventing the onset of DBD.

A cell line, termed ZFIN, was established from the caudal fin of zebrafish and was shown to be susceptible to spring viremia of carp virus (SVCV). The ZFIN cells are epithelial like cells and have a moderate plasmid transfection efficiency of 13.9%. Using an RNA-seq approach, differentially expressed genes (DEGs) regulated by SVCV were identified. Infection of SVCV gave rise to 3931 DEGs and up-regulated DEGs were mostly enriched into the biological regulation and cellular processes, among which pathways for the type I interferon signaling and the response to exogenous dsRNA were the top two GO terms. Several KEGG signaling pathways including TLR signaling pathway, RLR receptor signaling pathway, cytosolic DNA-sensing pathway, NLR signaling pathway, cytokine-cytokine receptor interaction and ferroptosis were significantly enriched. Antiviral genes including ifnφ1, isg15 and mx were significantly up-regulated. In addition, key DEGs involved in autophagy were identified. The results indicate that the ZFIN cell line provides a useful in vitro tool for study on the gene functions and cellular responses to viral infection in fish.

Abstract PARP inhibitors (PARPi) hold substantial promise in treating glioblastoma (GBM). However, the adverse effects have restricted their broad application. Through unbiased transcriptomic and proteomic sequencing, it is discovered that the BET inhibitor (BETi) Birabresib profoundly alters the processes of DNA replication and cell cycle progression in GBM cells, beyond the previously reported impact of BET inhibition on homologous recombination repair. Through in vitro experiments using established GBM cell lines and patient‐derived primary GBM cells, as well as in vivo orthotopic transplantation tumor experiments in zebrafish and nude mice, it is demonstrated that the concurrent administration of PARPi and BETi can synergistically inhibit GBM. Intriguingly, it is observed that DNA damage lingers after discontinuation of PARPi monotherapy, implying that sequential administration of PARPi followed by BETi can maintain antitumor efficacy while reducing toxicity. In GBM cells with elevated baseline replication stress, the sequential regimen exhibits comparable efficacy to concurrent treatment, protecting normal glial cells with lower baseline replication stress from DNA toxicity and subsequent death. This study provides compelling preclinical evidence supporting the development of innovative drug administration strategies focusing on PARPi for GBM therapy.

Abstract Oral squamous cell carcinoma (OSCC) stands as a predominant and perilous malignant neoplasm globally, with the majority of cases originating from oral potential malignant disorders (OPMDs). Despite this, effective strategies to impede the progression of OPMDs to OSCC remain elusive. In this study, we established mouse models of oral carcinogenesis via 4‐nitroquinoline 1‐oxide induction, mirroring the sequential transformation from normal oral mucosa to OPMDs, culminating in OSCC development. By intervening during the OPMDs stage, we observed that combining PD1 blockade with photodynamic therapy (PDT) significantly mitigated oral carcinogenesis progression. Single‐cell transcriptomic sequencing unveiled microenvironmental dysregulation occurring predominantly from OPMDs to OSCC stages, fostering a tumor‐promoting milieu characterized by increased Treg proportion, heightened S100A8 expression, and decreased Fib_Igfbp5 (a specific fibroblast subtype) proportion, among others. Notably, intervening with PD1 blockade and PDT during the OPMDs stage hindered the formation of the tumor‐promoting microenvironment, resulting in decreased Treg proportion, reduced S100A8 expression, and increased Fib_Igfbp5 proportion. Moreover, combination therapy elicited a more robust treatment‐associated immune response compared with monotherapy. In essence, our findings present a novel strategy for curtailing the progression of oral carcinogenesis.

The FUS::DDIT3 fusion protein, formed by the chromosomal translocation t (12;16) (q13;p11), is found in over 90% of myxoid liposarcoma (MLS) cases and is a crucial protein in its development. Many studies have explored the role of FUS::DDIT3 in MLS, and the prevailing view is that FUS::DDIT3 inhibits adipocyte differentiation and promotes MLS growth and invasive migration by functioning as an aberrant transcription factor that affects gene expression and regulates its downstream molecules. As fusion proteins are gradually showing their potential as targets for precision cancer therapy, FUS::DDIT3 has also been investigated as a therapeutic target. Drugs that target FUS::DDIT3 and its downstream molecules for treating MLS are widely utilized in both clinical practice and experimental studies, and some of them have demonstrated promising results. This article reviews the findings of relevant research, providing an overview of the oncogenic mechanisms of the FUS::DDIT3 fusion protein in MLS, as well as recent advancements in its therapy.

Abstract Osteoporosis (OP) is a systematic bone disease characterized by low bone mass and fragile bone microarchitecture. Conventional treatment for OP has limited efficacy and long‐term toxicity. Synthetic biology makes bacterial extracellular vesicle (BEVs)‐based therapeutic strategies a promising alternative for the treatment of OP. Here, we constructed a recombinant probiotics Escherichia coli Nissle 1917‐pET28a‐ClyA‐BMP‐2‐CXCR4 (ECN‐pClyA‐BMP‐2‐CXCR4), in which BMP‐2 and CXCR4 were overexpressed in fusion with BEVs surface protein ClyA. Subsequently, we isolated engineered BEVs‐BMP‐2‐CXCR4 (BEVs‐BC) for OP therapy. The engineered BEVs‐BC exhibited great bone targeting in vivo. In addition, BEVs‐BC had good biocompatibility and remarkable ability to promote osteogenic differentiation of BMSCs. Finally, the synthetic biology‐based BEVs‐BC significantly prevented the OP in an ovariectomized (OVX) mouse model. In conclusion, we constructed BEVs‐BC with both bone‐targeting and bone‐forming in one‐step using synthetic biology, which provides an effective strategy for OP and has great potential for industrialization.

Compared to conventional spoofing, emerging spoofing attacks pose a heightened threat to security applications within the global navigation satellite system (GNSS) due to their subtly designed signal structures. In response, a novel spoofing detection method entitled aggregated correlation residue likelihood analysis (A-CoRLiAn) is proposed in this study. Requiring only the addition of a pair of supplementary correlators, A-CoRLiAn harnesses correlation residues to formulate a likelihood metric, subsequently aggregating weighted decisions from all tracked satellites to ascertain the presence of spoofing. Evaluated under six diverse spoofing scenarios (including emerging challenges) in the Texas Spoofing Test Battery (TEXBAT) via Monte Carlo simulations, A-CoRLiAn yields a detection rate of 99.71%, demonstrating sensitivity, robustness, autonomy, and a lightweight architecture conducive to real-time implementation against spoofing threats.

To achieve cost-effective micro-/nano-displacement adjustment, this paper integrates the advantages of flexible hinge micro-/nano-displacement transmission. A linear stepper motor is utilized as the driving component to design and develop a high-precision, low-cost micro-/nano-positioning system. The structure, design, and working principles of the micro-/nano-positioning platform are introduced. The scaling factor model between micro-positioning platforms and nano-positioning platforms is analyzed. Static and dynamic models of flexible mechanisms have been established. The dimensions of the mechanical structure and the selection of motors are determined. The mechanical characteristics of the micro-/nano-positioning platform are validated through finite element analysis. To address the characteristic of increasing loads during the transmission process, an intelligent control system based on current feedback is designed and developed. The integration of drive and control provides a high level of system integration. Finally, experimental calibration was conducted to test the motion characteristics of the linear stepper motor-driven micro-/nano-positioning platform. It achieved a minimum displacement control resolution of 100 nm and demonstrated a certain level of stability.

ObjectiveTo examine the prevalence and influencing factors of multimorbidity among community diabetic patients in six provincial-level administrative divisions (PLADs) of China for providing evidence to disease management and multimorbidity prevention in the patients. MethodsUsing stratified multistage random sampling, we selected 6 713 adult patients ( ≥ 18 years) with type 2 diabetics registered in local basic public health service systems in urban communities and rural villages in Tianjin and Chongqing municipality and Guangdong, Hubei, Heilongjiang, Gansu province. Relevant information of the participants were collected via face-to-face surveys with a self-designed questionnaire from December 2021 to March 2022 and analyzed using descriptive statistics and logistic regression. ResultsMultimorbidity was reported by 3235 (51.93%) of the 6230 patients with eligible responses. The top three most reported multimorbidities were hypertension (reported by 44.77% of the patients), coronary heart disease (12.34%) and stroke (4.65%) and the number (proportion) of the patients with one, two, and three or more multimorbidities were 2190 (35.15%), 754 (12.10%), and 291 (4.67%), respectively, with the most prevalent multimorbidity of diabetes and hyperten-sion reported by 29.15% of the patients. Multivariate unconditional logistic regression analysis indicated that aged 45 years and older, living in northern regions, having alcohol consumption and a diabetes duration of 10 years and more were significant risk factors for multimorbidity; whereas, being married was a significant protective factor. ConclusionThe prevalence of chronic disease comorbidity is relatively high and mainly influenced by age, marital status, living region, alcohol consumption and diabetes duration among community diabetic patients in urban and rural areas of six PLADs in China.

In order to improve the accuracy of the transformer fault identification using nature-inspired algorithms, an identification method based on the GWO (Grey Wolf Optimizer)-optimized Dual-channel MLP (Multilayer Perceptron)-Attention is proposed. First, a Dual-channel model is constructed by combining the AM (Attention Mechanism) and MLP. Subsequently, the GWO algorithm is used to optimize the number and the nodes of the hidden layer in the Dual-channel MLP-Attention model. Typical transformer faults are simulated using DDRTS (Digital Dynamic Real-Time Simulator) system. Experiments showed that the GWO- optimized method has an accuracy rate of 95.3%-96.7% in identifying the transformer faults. Compared with BP, SVM, MLP, and single-channel M-A models, the proposed method improved the accuracy by14.1%, 9.6%, 9.3%, and 3.3% respectively. This result indicates the rationality and effectiveness of the proposed method in transformer fault identification.

Introduction: The application prospects of percutaneous endoscopic lumbar discectomy (PELD) as a minimally invasive spinal surgery method in the treatment of lumbar disc herniation are extensive. This study aims to find the optimal entry angle for the trephine at the L4/5 intervertebral space, which causes less lumbar damage and has greater postoperative stability. To achieve this, we conduct a three-dimensional simulated analysis of the degree of damage caused by targeted puncture-based trephine osteotomy on the lumbar spine.Methods: We gathered clinical CT data from patients to construct a lumbar model. This model was used to simulate and analyze the variations in trephine osteotomy volume resulting from targeted punctures at the L4/5 interspace. Furthermore, according to these variations in osteotomy volume, we created Finite Element Analysis (FEA) models specifically for the trephine osteotomy procedure. We then applied mechanical loads to conduct range of motion and von Mises stress analyses on the lumbar motion unit.Results: In percutaneous endoscopic interlaminar discectomy, the smallest osteotomy volume occurred with a 20° entry angle, close to the base of the spinous process. The volume increased at 30° and reached its largest at 40°. In percutaneous transforaminal endoscopic discectomy, the largest osteotomy volume was observed with a 50° entry angle, passing through the facet joints, with smaller volumes at 60° and the smallest at 70°. In FEA, M6 exhibited the most notable biomechanical decline, particularly during posterior extension and right rotation. M2 and M3 showed significant differences primarily in rotation, whereas the differences between M3 and M4 were most evident in posterior extension and right rotation. M5 displayed their highest stress levels primarily in posterior extension, with significant variations observed in right rotation alongside M4.Conclusion: The appropriate selection of entry sites can reduce lumbar damage and increase stability. We suggest employing targeted punctures at a 30° angle for PEID and at a 60° angle for PTED at the L4/5 intervertebral space. Additionally, reducing the degree of facet joint damage is crucial to enhance postoperative stability in lumbar vertebral motion units.

Different modified atmosphere packaging bags combined with low temperature treatment were used to store and preserve freshness of Chimonabambusa quadrangularis shoots to investigate the optimal preservation process of freshness of Chimonabambusa quadrangularis shoots. The freshness of Chimonabambusa quadrangularis shoots were stored in four different modified atmosphere packaging bags (WK, PE20, PE30, PE40) for 50 d in a cool storage facility at (1.0±0.3) ℃. The respiration intensity, hardness, browning index, polyphenols, soluble protein, PAL and POD of freshness of Chimonabambusa quadrangularis shoots were measured by sampling every 10 d during storage. And the effect of preservation of freshness of Chimonabambusa quadrangularis shoots by different modified atmosphere packaging bags was analyzed by combining with principal component analysis. The results showed that: PE20 could effectively reduce the respiration intensity of freshness of Chimonabambusa quadrangularis shoots, inhibit the rise of hardness, delay the change of total color difference value of fresh bamboo shoots, and inhibit the rise of decay rate, browning index, POD activity and PAL activity during storage of fresh bamboo shoots. The nutrients (VC, soluble protein) of freshness of Chimonabambusa quadrangularis shoots were maintained at a high level. Principal component analysis showed that respiration intensity, medium hardness, and decay rate were the key indicators affecting the freshness of Chimonabambusa quadrangularis shoots. The results of the analysis were subjected to a composite evaluation score, and the composite evaluation score of PE20 packaging at 50 d was higher than that of the other three modified atmosphere packages. The combined index determination and principal component analysis concluded that the treatment with modified atmosphere packaging bags of PE20 was the most effective in preserving freshness of Chimonabambusa quadrangularis shoots.

The model of distributed PV is constructed firstly, then the characteristics of distributed PV are studied and the electromechanical transient current equations are given. Using the actual PV grid-connected controller, a simulation system based on PSASP simulation platform is built. Through this system, the transient power characteristics of distributed PV during low voltage ride-through period are studied. Through theoretical analysis and experimental verification, the fault characteristics of distributed photovoltaic power supply are comprehensively expounded.

Oral squamous cell carcinoma (OSCC) stands as a prevalent subtype of head and neck squamous cell carcinoma, leading to disease recurrence and low survival rates. PPARγ, a ligand-dependent nuclear transcription factor, holds significance in tumor development. However, the role of PPARγ in the development of OSCC has not been fully elucidated. Through transcriptome sequencing analysis, we discovered a notable enrichment of ferroptosis-related molecules upon treatment with PPARγ antagonist. We subsequently confirmed the occurrence of ferroptosis through transmission electron microscopy, iron detection, etc. Notably, ferroptosis inhibitors could not completely rescue the cell death caused by PPARγ inhibitors, and the rescue effect was the greatest when disulfidptosis and ferroptosis inhibitors coexisted. We confirmed that the disulfidptosis phenotype indeed existed. Mechanistically, through qPCR and Western blotting, we observed that the inhibition of PPARγ resulted in the upregulation of heme oxygenase 1 (HMOX1), thereby promoting ferroptosis, while solute carrier family 7 member 11 (SLC7A11) was also upregulated to promote disulfidptosis in OSCC. Finally, a flow cytometry analysis of flight and multiplex immunohistochemical staining was used to characterize the immune status of PPARγ antagonist-treated OSCC tissues in a mouse tongue orthotopic transplantation tumor model, and the results showed that the inhibition of PPARγ led to ferroptosis and disulfidptosis, promoted the aggregation of cDCs and CD8+ T cells, and inhibited the progression of OSCC. Overall, our findings reveal that PPARγ plays a key role in regulating cell death in OSCC and that targeting PPARγ may be a potential therapeutic approach for OSCC.

In this paper, the design of an atmospheric turbulence simulation system for free-space optical (FSO) communication is proposed. The system can accurately simulate repeatable atmospheric turbulent fading channels. It has a dynamic execution range of 30 dB with an execution rate of 1 MHz. The execution accuracy of the system is higher than 0.1 dB. In addition, the reliable TCP/IP protocol is used for communication, which ensures the convenience and versatility of the system. Experiments are carried out to investigate the performance of the system, and the results prove its superiority. Hence, the atmospheric turbulence simulation system can effectively simulate the influence of atmospheric turbulence channels on FSO communication systems.

In pulpitis, dentinal restorative processes are considerably associated with undifferentiated mesenchymal cells in the pulp. This study aimed to investigate strategies to improve the odonto/osteogenic differentiation of dental pulp stem cells (DPSCs) in an inflammatory environment. After pretreatment of DPSCs with 20 ng/mL tumor necrosis factor-induced protein-6 (TSG-6), DPSCs were cultured in an inflammation-inducing solution. Real-time polymerase chain reaction and Western blotting were performed to measure the expression levels of nuclear factor kappa B (NF-κB) and odonto/osteogenic differentiation markers, respectively. Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine assays were used to assess cell proliferation and activity. Subcutaneous ectopic osteogenesis and mandibular bone cultures were performed to assess the effects of TSG-6 in vivo. The expression levels of odonto/osteogenic markers were higher in TSG-6-pre-treated DPSCs than nontreated DPSCs, whereas NF-κB-related proteins were lower after the induction of inflammation. An anti-CD44 antibody counteracted the rescue effect of TSG-6 on DPSC activity and mineralization in an inflammatory environment. Exogenous administration of TSG-6 enhanced the anti-inflammatory properties of DPSCs and partially restored their mineralization function by inhibiting NF-κB signaling. The mechanism of action of TSG-6 was attributed to its interaction with CD44. These findings reveal novel mechanisms by which DPSCs counter inflammation and provide a basis for the treatment of pulpitis.

With the rapid development of the power system and increasing demand for intelligence, substation operation training has received more attention. Action recognition is a monitoring and analysis system based on computer vision and artificial intelligence technology that can automatically identify and track personnel actions in video frames. The system accurately identifies abnormal behaviors such as illegal operations and provides real-time feedback to trainers or surveillance systems. The commonly adopted strategy for action recognition is to first extract human skeletons from videos and then recognize the skeleton sequences. Although graph convolutional networks (GCN)-based skeleton-based recognition methods have achieved impressive performance, they operate in spatial dimensions and cannot accurately describe the dependence between different time intervals in the temporal dimension. Additionally, existing methods typically handle the temporal and spatial dimensions separately, lacking effective communication between them. To address these issues, we propose a skeleton-based method that aggregates convolutional information of different scales in the time dimension to form a new scale dimension. We also introduce a space-time-scale attention module that enables effective communication and weight generation between the three dimensions for prediction. Our proposed method is validated on public datasets NTU60 and NTU120, with experimental results verifying its effectiveness. For substation operation training, we built a real-time recognition system based on our proposed method. We collected over 400 videos for evaluation, including 5 categories of actions, and achieved an accuracy of over 98%.

Neutrophils comprise the majority of immune cells in human peripheral circulation, have potent antimicrobial activities, and are clinically significant in their abundance, heterogeneity, and subcellular localization. In the past few years, the role of neutrophils as components of the innate immune response has been studied in numerous ways, and these cells are crucial in fighting infections, autoimmune diseases, and cancer. T-helper 17 (Th17) cells that produce interleukin 17 (IL-17) are critical in fighting infections and maintaining mucosal immune homeostasis, whereas they mediate several autoimmune diseases. Neutrophils affect adaptive immune responses by interacting with adaptive immune cells. In this review, we describe the physiological roles of both Th17 cells and neutrophils and their interactions and briefly describe the pathological processes in which these two cell types participate. We provide a summary of relevant drugs targeting IL-17A and their clinical trials. Here, we highlight the interactions between Th17 cells and neutrophils in diverse pathophysiological situations.

AIM: To determine whether an antisense RNA corresponding to the human Alu transposable element (Aluas RNA) can protect human lens epithelial cells (HLECs) from methylglyoxal-induced apoptosis. METHODS: Cell counting kit-8 (CCK-8) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to assess HLEC viability. HLEC viability/death was detected using a Calcein-AM/PI double staining kit; the annexin V-FITC method was used to detect HLEC apoptosis. The cytosolic reactive oxygen species (ROS) levels in HLECs were determined using a reactive species assay kit. The levels of malondialdehyde (MDA) and the antioxidant activities of total-superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) were assessed in HLECs using their respective kits. RT-qPCR and Western blotting were used to measure mRNA and protein expression levels of the genes. RESULTS: Aluas RNA rescued methylglyoxal-induced apoptosis in HLECs and ameliorated both the methylglyoxal-induced decrease in Bcl-2 mRNA and the methylglyoxal-induced increase in Bax mRNA. In addition, Aluas RNA inhibited the methylglyoxal-induced increase in Alu sense RNA expression. Aluas RNA inhibited the production of ROS induced by methylglyoxal, restored T-SOD and GSH-Px activity, and moderated the increase in MDA content after treatment with methylglyoxal. Aluas RNA significantly restored the methylglyoxal-induced down-regulation of Nrf2 gene and antioxidant defense genes, including glutathione peroxidase, heme oxygenase 1, γ-glutamylcysteine synthetase and quinone oxidoreductase 1. Aluas RNA ameliorated methylglyoxal-induced increases of the mRNA and protein expression of Keap1 that is the negative regulator of Nrf2. CONCLUSION: Aluas RNA reduces apoptosis induced by methylglyoxal by enhancing antioxidant defense.

Objective: By comparing and analyzing the quality of agate red cherries in different regions of Guizhou Province, the quality differences of these cherries in different areas could be obtained. Methods: The fresh fruits of agate red cherries from Kaiyang, Nayong and Zhijin were picked at the same maturity period, then the fruit weight, soluble solids, total flavonoids, polyphenol and related enzyme activities were measured. Results: From the appearance of the fruit, there was no significant difference in the size of the cherry fruit in the three regions, but the color of the cherry fruit in Nayong was relatively red. In terms of texture, the hardness of cherry fruit in Nayong area was 861.14 g, which was 1.82 times and 1.5 times of Zhijin and Kaiyang respectively. From the nutritional value, the highest free amino acid content of cherry fruit in Zhijin was 46.01 mg∙100 g−1. For the determination of metal ions, the selenium content in Kaiyang area was 153.51 μg/g, which was 11 times of Nayong and 1.27 times of Zhijin. From different aspects, the cherry fruits in the three regions had their own advantages, and the appearance of cherry fruits in Nayong region was relatively good, while the free amino acid and metal ion content of cherry fruits in Zhijin and Kaiyang areas were relatively high. This may be due to the differences in geographical location, climatic conditions and other factors, resulting in certain differences in nutritional value and fruit shape of cherry fruits in the three regions.

With the improved quality of life, oral health is under increased pressure. Numerous common oral mucosal diseases, such as oral lichen planus(OLP) and gingivitis, are related to the destruction of the oral immune barrier. The cytokines secreted by T-helper 17 (Th17) cells are essential for maintaining oral immune homeostasis and play essential roles in immune surveillance. When antigens stimulate the epithelium, Th17 cells expand, differentiate, and generate inflammatory factors to recruit other lymphocytes, such as neutrophils, to clear the infection, which helps to maintain the integrity of the epithelial barrier. In contrast, excessive Th17/IL-17 axis reactions may cause autoimmune damage. Therefore, an in-depth understanding of the role of Th17 cells in oral mucosa may provide prospects for treating oral mucosal diseases. We reviewed the role of Th17 cells in various oral and skin mucosal systemic diseases with oral characteristics, and based on the findings of these reports, we emphasize that Th17 cellular response may be a critical factor in inflammatory diseases of the oral mucosa. In addition, we should pay attention to the role and relationship of “pathogenic Th17” and “non-pathogenic Th17” in oral mucosal diseases. We hope to provide a reference for Th17 cells as a potential therapeutic target for treating oral mucosal inflammatory disorders in the future.

The increasing uncertainty of wind power brings greater challenges to the control for mitigation of cascading failures. In order to minimize the risk of cascading failures in large-scale wind power systems at a lower economic cost, a multi-stage blocking control model is proposed based on sensitivity analysis. Firstly, the propagation mechanism of cascading failures in power systems with wind power integration is analyzed, and the propagation path of such failures is predicted. Subsequently, sensitive lines that are prone to failure are identified using the power sensitivity matrix, taking into account the effects of blocking control on the propagation path. By constraining the power flow of these sensitive lines, a multi-stage blocking control model for the predicted cascading failure path is proposed with the objective of minimizing the control cost and cascading failure probability. Based on probabilistic optimal power flow calculations, the constraints related to wind power uncertainty are transformed into opportunity constraints. To validate the effectiveness of the proposed model, the IEEE 39-node system is used as an example, and the results show that the obtained control method is able to balance economy and safety. In addition, the control costs for the same initial failure are higher as the wind power penetration rates and confidence levels increase.

Abstract Oral submucous fibrosis (OSF) is a chronic and insidious oral potentially malignant disorder associated with a 4–17% risk of oral squamous cell carcinoma (OSCC). Our previous study found that proteasomal activator 28 gamma (PA28γ) is frequently overexpressed in oral squamous cell carcinoma and negatively correlated with poor patient prognosis. However, the role of PA28γ in the occurrence and development of OSF remains unclear. Here, we screened PA28γ-related genes and investigated their function in OSF. We demonstrated that the expression of PA28γ was positively associated with MEK1 and gradually elevated from normal to progressive stages of OSF tissue. Arecoline, a pathogenic component of OSF, could upregulate the protein levels of PA28γ and phosphorylated MEK1 and contribute to epithelial to mesenchymal transition (EMT) in epithelial cells. Notably, PA28γ could interact with MEK1 and upregulate its phosphorylation level. Furthermore, arecoline upregulated BRAF, which can interact with PA28γ and upregulate its protein level. Additionally, BRAF, PA28γ, and MEK1 could form protein complexes and then enhance the MEK1/ERK signaling pathways. The concrete mechanism of the protein stability of PA28γ is that BRAF mediates its degradation by inhibiting its ubiquitination. These findings underscore the instrumental role of PA28γ in the BRAF/MEK1 pathway and enhanced EMT through MEK1/ERK activation in OSF.

Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world, the 5-year survival rate of patients with HNSCC is still about 50% due to frequent metastasis and recurrence. Circular RNAs (circRNAs) have been characterized as key regulators of gene expression in numerous malignancies. However, the role of circRNA in HNSCC metastasis remains largely unknown. Here, we demonstrated that the circRFWD3 was significantly upregulated in HNSCC tissues and cell lines by circRNA microarray analysis and qPCR. Notably, high expression of circRFWD3 is related to highly aggressive HNSCC cell lines and lymph node metastasis in HNSCC patients. After that, Sanger sequencing, RNase R, and actinomycin D assay were performed to verify the ring structure of circRFWD3. Then functional experiments found it could promote the metastasis of HNSCC cells both in vitro and in vivo. Mechanistically, a dual-luciferase reporter assay, FISH, RIP, RNA pull-down, RNA-seq, and western blot experiments were employed and found that circRFWD3 served as a miRNAs sponge for miR-27a/27b, leading to the upregulation of PPARγ, and then promoted HNSCC metastasis via NF-κB/MMP13 pathway. Finally, ISH and IHC were carried out to determine the expression levels and clinical significances of circRFWD3 and PPARγ in clinical cohorts of HNSCC. According to the analysis results from two independent HNSCC cohorts, upregulated expression of circRFWD3 and PPARγ were positively associated with worse survival in patients with HNSCC. Overall, our results uncover that circRFWD3 acts a critical role in promoting the aggressiveness of HNSCC cells and is a prognostic marker for the disease, indicating that circRFWD3 may act as a potential therapeutic target in HNSCC.

Delignification is an effective pretreatment for new bamboo materials. The process creates pores in the wood and renders it more stable. Herein we propose a bamboo-epoxy resin composite material with enhanced strength and stability. The natural bamboo was first delignified and impregnated with resin, after which it was cured rapidly and allowed to contract after microwave heating to form a dense and uniform bamboo-epoxy resin composite material. The effects of different delignification times on the performance of the bamboo-epoxy resin were investigated. The composite material showed superior stability compared with natural bamboo. After 8 h of delignification, the flexural strength and compressive strength along the grain of the bamboo-epoxy resin had increased by 80.9% and 42.9%, respectively. This eco-friendly approach to creating high-performance material is useful for the fabrication of structural materials.

Chinese cherries, with their delightful blend of sourness and sweetness, are highly favored for their taste and nutritional benefits. However, they mature in conditions of high temperatures and rainfall, making them vulnerable to fungal infections which compromise their post-harvest quality. Our research aimed to study the effects of pre-harvest spraying with salicylic acid (SA) and sodium nitroprusside (SNP) on the pathogenic fungi in Manaohong cherries and their subsequent storage quality. We discovered that using SA and SNP at varying fruit development stages preserved fruit hardness, texture, appearance, and respiratory rate during storage, although it did not significantly alter the fruit’s dimensions. Furthermore, this pre-harvest treatment preserved levels of titratable acids, total phenols, and other antioxidants in the cherries, bolstered the activities of certain antioxidant enzymes (SOD, APX), and inhibited the activity of PPO and POD enzymes.Notably, the SA treatment alone demonstrated superior storage performance compared to combined treatments. Our research also identified Alternaria alternata and Colletotrichum godetiae as the primary pathogens in Manaohong cherries. In in vitro experiments, neither SA nor SNP inhibited these fungi’s growth. Consequently, we evaluated 12 pesticides and determined that 5% hexaconazole and 50% benomyl were most effective against these pathogens. Thus, to enhance the shelf life of Manaohong cherries and ensure their post-harvest quality, we recommend a pre-harvest spray of a SA, and combined with 5% hexaconazole and 50% benomyl. This approach not only promises enhanced cherry longevity but also lays a foundational strategy for the flourishing Manaohong Cherry industry.

The comprehensive exploration and thorough understanding of the physicochemical characteristics of “Crystal” grapes in the Karst area of Southwest China can not only produce edible table grapes, but also offer significant theoretical backing for the management of rocky desertification in the Karst area and consequently generate enhanced social and ecological benefits. This study explored the regulatory effect of 1-MCP fumigation on the postharvest storage quality of "Crystal” grapes, aiming to provide some technical support for the development of the grape industry in the Karst mountainous areas. The results indicate that compared with the control group, both the 10.0 and 50.0 μL/L 1-MCP treatment groups effectively inhibited the increase in decay rate, browning rate, shedding rate, and color change of the grapes, significantly inhibited the enhancement of polyphenol oxidase (PPO), peroxidase (POD), and lipoxygenases (LOX) browning-related enzyme activities, improved the superoxide dismutase (SOD) activity of the fruits, hindered the decrease of ascorbic acid (AsA) and polyphenols, delayed the accumulation of malondialdehyde (MDA) content, and significantly postponed the peak period of polygalacturonase (PG) activity in the fruits and the degradation of protopectin to soluble pectin, thereby maintaining desirable texture characteristics. The utilization of 1-MCP for fruit fumigation yielded a heightened overall fragrance, thereby facilitating the emission of terpenes, alcohols, aldehydes, ketone aromatic compounds, and methyl aromatic substances within the fruit. Overall, both the M10 and M50 treatments are equally effective in preserving the storage quality of “Crystal” grapes. Under the condition of ensuring the excellent edible quality of crystal grapes, M2 can extend the shelf life of crystal grapes by about 5 days, and M10 and M50 can extend the storage period of crystal grapes by 10~15 days. Considering the cost, it is recommended that the industry employs a concentration of 10.0 μL/L of 1-MCP for “Crystal” grapes. Simultaneously, this study also provides theoretical support for the ecologically high-quality development of cultivated land in the Karst mountainous area of Guizhou and tree selection.

Highlights ABCB1 overexpression significantly desensitized both drug-selected and gene-transfected cells, which overexpress ABCB1, to OTS964 and that this drug resistance can be antagonized by verapamil, a known ABCB1 inhibitor. Consistently, a similar trend was observed in tumor-bearing mice. OTS964 stimulated ATPase activity of ABCB1 and upregulated expression levels of ABCB1, resulting in induced resistance to other ABCB1 substrate-drugs, such as paclitaxel. OTS964 received a comparable affinity score and can dock into the substrate-binding site of human ABCB1 protein.

Abstract Alterations in DNAs could not reveal what happened in proteins. The accumulated alterations of DNAs would change the manifestation of proteins. Therefore, as is the case in cancer liquid biopsies, deep proteome profiling will likely provide invaluable and clinically relevant information in real-time throughout all stages of cancer progression. However, due to the great complexity of proteomes in liquid biopsy samples and the limitations of proteomic technologies compared to high-plex sequencing technologies, proteomic discoveries have yet lagged behind their counterpart, genomic technologies. Therefore, novel protein technologies are in urgent demand to fulfill the goals set out for biomarker discovery in cancer liquid biopsies. Notably, conventional and innovative technologies are being rapidly developed for proteomic analysis in cancer liquid biopsies. These advances have greatly facilitated early detection, diagnosis, prognosis, and monitoring of cancer evolution, adapted or adopted in response to therapeutic interventions. In this paper, we review the high-plex proteomics technologies that are capable of measuring at least hundreds of proteins simultaneously from liquid biopsy samples, ranging from traditional technologies based on mass spectrometry (MS) and antibody/antigen arrays to innovative technologies based on aptamer, proximity extension assay (PEA), and reverse phase protein arrays (RPPA).

The energy crisis and environmental problems have attracted global attention, thus the photovoltaic (PV) power generation technology comes to people’s mind. The application of unmanned aerial vehicle (UAV) inspection technology can overcome the disadvantages of large scale and high risk of this project. The application of unmanned aerial vehicle (UAV) infrared detection technology in PV power generation can not only improve work efficiency, but also have high economic benefits. This paper based on U-Net network and HSV space, proposes a method of PV infrared image segmentation and location detection of hot spots, which is used to detect and analyze the shielding of PV panels. Firstly, the main PV modules are automatically split from the different infrared image background based on U-Net. In order to quickly locate the defection location, the mask image is multiplied by the original image and then converted to HSV. The discriminant of bright spot features is introduced, and the discriminant mechanism is summarized according to the experiment, and the formation reason is analyzed. The experiment result shows that the method is not affected by the infrared image under the different background, provides data for the maintenance of power station and improves the detection accuracy. The accuracy rate of analyzing the causes of defects is 92.5%.

Oral inflammatory diseases, including oral lichen planus (OLP) and recurrent aphthous ulcer (RAU), seriously affect the patient’s quality of life. Due to the lack of ideal disease models, it is difficult to determine whether novel immunotherapy strategies are effective in treating oral inflammatory diseases. Here, we show that the deficiency of Foxp3 or IL-2 caused oral mucosa inflammation in mice, proving that Treg cells are important in maintaining the immune homeostasis in the oral mucosa. Then we determined that adoptive transfer of CD4+CD25-CD45Rbhigh T cells could induce oral inflammation in Rag1-/- mice, and co-transfer of Treg cells together with CD4+CD25-CD45Rbhigh T cells could suppress the development of oral inflammation in this mouse model. Our study showed that adoptive transfer of CD4+CD25-CD45Rbhigh T cells into Rag1-/- mice could be a novel disease model of oral inflammation. Our data provides direct evidence that Treg cell therapy is effective in suppressing oral mucosa inflammation in mice. Therefore, Treg cell therapy may be a promising novel strategy to treat oral inflammatory diseases.

The senescence-associated secretory phenotype (SASP), which accumulates over the course of normal aging and in age-related diseases, is a crucial driver of chronic inflammation and aging phenotypes. It is also responsible for the pathogenesis of multiple oral diseases. However, the pathogenic mechanism underlying SASP has not yet been fully elucidated. Here, relevant articles on SASP published over the last five years (2017–2022) were retrieved and used for bibliometric analysis, for the first time, to examine SASP composition. More than half of the relevant articles focus on various cytokines (27.5%), growth factors (20.9%), and proteases (20.9%). In addition, lipid metabolites (13.1%) and extracellular vesicles (6.5%) have received increasing attention over the past five years, and have been recognized as novel SASP categories. Based on this, we summarize the evidences demonstrating that SASP plays a pleiotropic role in oral immunity and propose a four-step hypothetical framework for the progression of SASP-related oral pathology—1) oral SASP development, 2) SASP-related oral pathological alterations, 3) pathological changes leading to oral immune homeostasis disruption, and 4) SASP-mediated immune dysregulation escalating oral disease. By targeting specific SASP factors, potential therapies can be developed to treat oral and age-related diseases.

PLAAT1 is a member of the PLAAT protein family and plays important roles in tumor suppression, transglutaminase activation and peroxisomal biogenesis. Recently, PLAAT1 has been shown to promote degradation of p53 protein and cellular organelles such as mitochondria, endoplasmic reticulum and lysosome. In this study, we show that PLAAT1 inhibits the production of type I interferon and promotes virus replication in zebrafish. Overexpression of Plaat1 in zebrafish cells suppresses antiviral responses and promotes virus replication. Mechanistically, PLAAT1 interacts with IRF3 and IRF7 to initiate degradation of IRF3 and IRF7, which can be attenuated by 3-methyladenine, an inhibitor of autophagosome. Our study provides novel insights into the functions of PLAAT1 in host immune response to viral infection.

Soft rot is a severe postharvest disease of kiwifruit that causes enormous economic losses annually. In this study, we aimed to explore an effective pullulan-based active coating, incorporating food additives to reduce soft rot and extend the shelf life of cold-stored kiwifruit. The results showed that 1 g/L potassium metabisulfite could completely inhibit the mycelial growth of Diaporthe sp., Botryosphaeria dothidea, Phomopsis sp. and Alternaria sp., which were the primary pathogens of kiwifruit soft rot. Furthermore, the pullulan coating, combined with a 10 g/L potassium metabisulfite group, had a decay rate 46% lower than the control (CK) group and maintained fruit quality at the end of shelf life. The retention of physicochemical properties such as soluble solid content (SSC), firmness, weight loss and respiration rate also confirmed the efficacy of the treatment. In addition, at the end of shelf life, pullulan coating, combined with potassium metabisulfite, increased the accumulation of total phenolic content (37.59%) and flavonoid content (9.28%), maintained a high energy charge (51.36%), and enhanced superoxide dismutase (SOD) (6.27%), peroxidase (POD) (62.50%), catalase (CAT) (84.62%) and phenylalanine ammonia lyase (PAL) (24.61%) enzyme activities as well as initiating the upregulation of their gene expression levels. As a result, the disease resistance of fruit was improved, and the occurrence of soft rot was delayed. Overall, this study demonstrated that using the pullulan-based active coating incorporating potassium metabisulfite treatment effectively controlled soft rot and retarded the senescence of postharvest kiwifruit.

To optimize the bamboo heat treatment process, the corresponding evolution rules under various heat treatment conditions must be determined. When the heat treatment time and temperature remained constant, the effects of different heat treatment pressures on the equilibrium moisture content, dimensional stability, mechanical properties, and chemical composition of bamboo were systematically investigated. In this experiment, bamboo without heat treatment was used as the control group. The experimental findings demonstrate the following: (1) The equilibrium moisture content of heat-treated bamboo gradually decreases with increasing treatment pressure. When the heat treatment pressure was set at 0.1, 0.15, 0.2, and 0.25 MPa, the bamboo’s equilibrium water content decreased to 12.1%, 11.7%, 9.9%, and 8.6%, respectively, while that of the control group was 13.8%. (2) The dimensional stability of bamboo was enhanced with increasing heat treatment pressure. At pressures of 0.1, 0.15, 0.2, and 0.25 MPa, the radial air-dry shrinkage rates of the heat-treated bamboo decreased to 3.4%, 3.4%, 2.6%, and 2.3%, respectively, while the tangential air-dry shrinkage rates reduced to 5.6%, 5.1%, 3.3%, and 3.0%. In comparison, the radial and tangential air-dry shrinkage rates of the control group were measured as 3.6% and 5.8%, respectively. Similarly, the radial and tangential full-dry shrinkage of bamboo exhibited a similar trend. (3) With the increase in heat treatment pressure, the bending strength and longitudinal compressive strength of bamboo exhibited an initial rise followed by a decline. When it was at heat treatment pressures of 0.1, 0.15, 0.2, and 0.25 MPa, the corresponding bending strengths of the heat-treated bamboo were measured as 41.2, 26.7, 22.4, and 20.4 MPa, respectively; while the longitudinal compressive strengths were recorded as 42.6, 38.1, 29.1, and 25.3 MPa. In comparison, the bending and longitudinal compressive strengths of the control group were measured as 39.8 and 38.5 MPa, respectively. It is evident that the optimal heat treatment pressure for bamboo is 0.1 MPa, resulting in a significant increase of 3.5% and 10.6% in bending strength and longitudinal compressive strength, respectively, compared to the control group. (4) Based on the FTIR and XRD patterns of bamboo samples, a range of physical and chemical transformations were observed during the heat treatment process, including cellulose adsorb water evaporation, hemicellulose and cellulose degradation, as well as acetyl group hydrolysis on the molecular chain of hemicellulose. These changes collectively impacted the physical and mechanical properties of bamboo.

Abstract ATP‐binding cassette (ABC) transporters superfamily mediates multidrug resistance in cancer by extruding structurally distinct chemotherapeutic agents, causing failure in chemotherapy. Among the 49 ABC transporters, multidrug resistance protein 7 (MRP7 or ABCC10) is relatively new and has been identified as the efflux pump of multiple anticancer agents including Vinca alkaloids and taxanes. Herein, we construct and validate a homology model for human MRP7 based on the cryo‐EM structures of MRP1. Structure–function relationship of MRP7 was obtained from molecular dynamics simulations and docking studies and was in accordance with previous studies of ABC transporters. The motion patterns correlated with efflux mechanism were discussed. Additionally, predicted substrate‐ and modulator‐binding sites of MRP7 were described for the first time, which provided rational insights in understanding the drug binding and functional regulation in MRP7. Our findings will benefit the high‐throughput virtual screening and development of MRP7 modulators in the future.

The composition, physicochemical properties, in vitro biological activity, and hypoglycemic activity exhibited by polysaccharides from four varieties of G. elata were investigated in this study; the four extracted GaE polysaccharides were termed as GaE-B (G. elata Bl. f. glauca S. chow polysaccharides), GaE-R (G. elata Bl. f. elata polysaccharides), GaE-Hyb (hybridization of G. elata Bl. f. glauca S. chow and G. elata Bl. f. elata polysaccharides), and GaE-G (G. elata Bl. f. viridis Makino polysaccharides). As revealed by the results, the GaE polysaccharides were found with the same monosaccharide composition, primarily including glucose, whereas the content of each variety was significantly different. In addition, different degrees of differences were found in the in vitro antioxidant and hypoglycemic activity, molecular weight, yield, and chemical composition exhibited by the abovementioned varieties. However, GaE-B and GaE-Hyb were found with similar physical properties, chemical composition, and antioxidant and hypoglycemic activity. GaE-R had the lowest yield, total sugar content, and molecular weight, whereas it involved higher xylose, binding protein, and polyphenols as well as higher antioxidant and hypoglycemic activity. In contrast, GaE-G was found with the highest yield, total sugar content, and molecular weight, whereas it contained the lowest xylose, binding protein, and polyphenols, as well as the weakest antioxidant and hypoglycemic activity. In brief, the polysaccharide of G. elata, a plant resource for homology of medicine and food, could more significantly enhance the biological activity of G. elata as it was released in the process of decocting and stewing. To be specific, the assessment of polysaccharide activity alone suggested that GaE-R was the best.

In this study, to investigate the physiological and molecular mechanisms of melatonin inhibiting the postharvest rot of blueberry fruits, blueberry fruits were dipped in 0.3 mmol L−1 melatonin solution for 3 min and stored at 0°C for 80 days. The results indicated that melatonin did not significantly (p > 0.05) inhibit the mycelial growth or spore germination of Alternaria alternata, Botrytis cinerea, and Colletotrichum gloeosporioides. In addition, an in vivo study revealed that melatonin treatment increased the enzymatic activities of phenylalanine ammonia lyase (PAL), cinnamate 4-hydroxylase (C4H), 4-coumarate-CoA ligase (4CL), cinnamyl alcohol dehydrogenase (CAD), polyphenol oxidase (PPO), and peroxidase (POD) in fruits. Furthermore, genes related to jasmonic acid synthesis were upregulated (VaLOX, VaAOS, and VaAOC), as were those related to pathogenesis-related proteins (VaGLU and VaCHT) and phenylpropane metabolism (VaPAL, VaC4H, Va4CL, VaCAD, VaPPO, and VaPOD), which promoted the accumulation of total phenols, flavonoids, anthocyanins, and lignin in the fruits. These results suggest that melatonin enhances the postharvest disease resistance of blueberry fruits by mediating the jasmonic acid signaling pathway and the phenylpropane pathway.

The acceptance of kiwifruit by consumers is significantly affected by its slow ripening and susceptibility to deterioration. Ready-to-eat “Guichang” kiwifruit and its preparation technology were studied by the regulation of ethylene and 1-MCP. Harvested kiwifruits were treated with 100–2000 μl L−1ethylene for 36 h (20°C) and then treatment with 0–0.5 μl L−1 1-MCP. The results showed that the preservation effect of 0.5 μl L−1 1-MCP is inefficient when the soluble solid content of kiwifruit exceeded 15%. The ethylene-treated fruits reached an “edible window” after 24 h, but a higher concentration of ethylene would not further improve ripening efficiency, while the optimal ethylene concentration was 250 μl L−1. Moreover, after 250 μl L−1 ethylene treatment, 0.5 μl L−1 1-MCP would effectively prolong the “edible window” of fruits by approximately 19 days. The volatile component variety and ester content of 0.5 μl L−1 1-MCP-treated fruits were not different from those of the CK group. Principal component analysis and hierarchical cluster analysis indicated that the eating quality of fruits treated with 0.5 μl L−1 1-MCP was similar to that of fruits treated with ethylene. Consequently, ready-to-eat “Guichang” kiwifruit preparation includes ripening with 250 μl L−1 (20°C, 36 h) ethylene without exceeding the 1-MCP threshold and then treated with 0.5 μl L−1 1-MCP (20°C, 24 h). This study highlights the first development of a facile and low-cost preparation technology for ready-to-eat “Guichang” kiwifruit, which could reduce the time for harvested kiwifruit to reach the “edible window” and prolong the “edible window” of edible kiwifruit.

Fresh bamboo shoots (Chimonobambusa quadrangularis) are subjected to senescence (e.g., lignification and browning) during postharvest storage. This study investigated the effects of 1-MCP and SO2 treatment on bamboo shoot senescence and its regulation mechanism in order to extend bamboo shoot storage time. 1-MCP and SO2 treatments significantly inhibited the browning and lignification of fresh bamboo shoots during storage, according to the results. Its lower browning index and lignin content are directly related to its lower lignin content compared to the CK control group. The browning index and lignin content of the 1-MCP + SO2 treatment during the late storage period were 90.55% and 81.50% of the CK treatment, respectively. The result of the in-depth analysis suggested that 1-MCP and SO2 treatments reduced nutrient loss and maintained the nutritional value of bamboo shoots by inhibiting respiration and physiological metabolism. The PPO activity was inhibited to inhibit the browning process. Moreover, the scavenging ability of ROS was enhanced, the accumulation of MDA was inhibited, and the senescence of bamboo shoots was delayed after higher contents of total flavonoids and ascorbic acid were maintained and the activities of ascorbic acid peroxidase and superoxide dismutase were stimulated. Furthermore, lignin biosynthesis was hindered, and the lignification of bamboo shoots was delayed after the activities of POD and PAL were inhibited. In brief, 1-MCP + SO2 treatment is capable of inhibiting the physiological metabolism, browning, and lignification of bamboo shoots, maintaining good quality during storage, and delaying the senescence of bamboo shoots. Clarifying the senescence mechanism of bamboo shoots is of great significance for expanding the bamboo shoot industry and slowing down rocky desertification in karst mountainous areas.

Dictyophora rubrovolvata is a typical edible fungus of Guizhou Province and is very popular due to its unique taste and texture. In this study, the effect of a controlled atmosphere (CA) on fresh-cut D. rubrovolvata shelf life was investigated. Firstly, this study addresses the influence of different O2 concentrations (5%, 20%, 35%, 50%, 65%, 80%, or 95%) with N2 balance on fresh-cut D. rubrovolvata quality while stored at 4 ± 1 °C for 7 d. Then, on the basis of the determined O2 concentration (5%), CO2 (0%, 5%, 10%, 15%, or 20%) was involved and stored for 8 d at 4 ± 1 °C. Evaluations of physiology parameters, texture, browning degree, nutritional, umami, volatile components, and total colony numbers were determined in fresh-cut D. rubrovolvata. From the results of water migration, the sample of 5% O2/5% CO2/90% N2 was closer to 0 d than other groups at 8 days. Meanwhile, the polyphenol oxidase (2.26 ± 0.07 U/(g·min)), and catalase activity (4.66 ± 0.08 U/(g·min·FW)) were superior to the samples of other treatment groups on the eighth day (3.04 ± 0.06 to 3.84 ± 0.10 U/(g·min), 4.02 ± 0.07 to 4.07 ± 0.07 U/(g·min·FW)). Therefore, we found that a gas environment with 5% O2/5% CO2/90% N2 could ensure the membrane integrity, oxidation, and prevent the browning of fresh-cut D. rubrovolvata, thus better maintaining the physiological parameters. Meanwhile, it also maintained the samples’ texture, color, nutritional value, and umami taste. Furthermore, it inhibited the increase in total colony numbers. The volatile components were closer to the initial level compared with other groups. The results indicate that fresh-cut D. rubrovolvata could maintain its shelf life and quality when stored in 5% O2/5% CO2/90% N2 at 4 ± 1 °C.

Objective: To investigate the effect of acupoint massage on the recovery of gastrointestinal function in patients after laparoscopic surgery for gynecologic indications. Methods: A total of 160 patients, who underwent gynecologic laparoscopy from December 2015 to January 2017, were recruited. Half of the patients received standard postoperative nursing (i.e., the control group); while the other half received acupoint massage in addition to the standard care (i.e., the observation group). The recovery time of bowel sounds, the first anal exhaust time and the first defecation time were recorded. The plasma levels of motilin, somatostatin and cholecystokinin before and after the surgery were also determined. Results: Compared to the control group, the observation group demonstrated significantly shorter bowel sound recovery time, first anal exhaust time and first defecation time (t = 11.755, 10.400, 11.950, P

Cisplatin (DDP) is a first-line chemotherapeutic drug applied for the treatment of oral squamous cell carcinoma (OSCC). The anticancer activity of DDP is tightly linked to its intracellular uptake. It is unwise to increase the DDP intake by increasing the dose or shortening the dosing interval because of the severe systemic toxicity (nephrotoxicity, ototoxicity and neurotoxicity) in DDP application. The main uptake pathways of DDP include passive diffusion and active transporter transport. Therefore, finding additional uptake pathways that can improve the effective intracellular concentration of DDP is critical. Macropinocytosis, an endocytic mechanism for extracellular material absorption, contributes to the intracellular uptake of anticancer drugs. No research has been conducted to determine whether macropinocytosis can augment the intracellular uptake of DDP in OSCC cells or not. Based on that, we proved for the first time that silmitasertib (previously CX-4945) could trigger macropinocytosis, which may increase the intracellular uptake of DDP and enhance apoptosis via in vivo and in vitro experiments. We hope that our findings will inspire a new approach for the application of DDP in cancer treatment.

BackgroundDamaged and dead cells release cell-free DNA (cfDNA) that activates cyclic GMP–AMP (cGAMP) synthase (cGAS), which leads to the activation of stimulator of interferon genes (STING) via the second messenger cGAMP. STING promotes the production of inflammatory cytokines and type I interferons to induce an inflammatory response. Oral lichen planus (OLP), a chronic autoimmune disease involving oral mucosa characterized by the apoptosis of keratinocytes mediated by T-lymphocytes, is related to the activation of multiple inflammatory signaling pathways. Currently, the relationship between cfDNA and OLP has not been confirmed. We hypothesized that cfDNA may be a potential therapeutic target for OLP.MethodscfDNA was extracted from the saliva and plasma of OLP patients; its concentration was measured using the Quanti-iT-PicoGree kit and its relationship with OLP inflammation was assessed. cfDNA of OLP patients (cfDNA-OLP) was transfected into THP-1 macrophages and the expression of inflammatory factors was investigated by performing quantitative real time PCR (qRT-PCR), western blotting, and enzyme-linked immunosorbent assay (ELISA). STING expression was analyzed in the tissues of OLP patients and healthy controls using immunohistochemical staining and western blotting. siRNA was used to knockdown STING expression in THP-1 macrophages, and the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) secreted by cells following cfDNA-OLP transfection were detected using ELISA. Finally, the effect of the cationic polymer PAMAM-G3 was evaluated on the treatment of inflammation induced by cfDNA-OLP.ResultsThe concentration of cfDNA in the saliva and plasma of OLP patients was considerably higher than that of healthy controls, and it positively correlated with the levels of inflammatory cytokines and clinical characteristics. cfDNA-OLP induced an inflammatory response in THP-1 macrophages. STING expression was significantly higher in OLP tissues than in the gingival tissues of healthy controls. STING knockdown suppressed cfDNA-OLP-induced inflammation in THP-1 macrophages. PAMAM-G3 inhibited the inflammatory response caused by cfDNA-OLP.ConclusionThe cfDNA level is increased in OLP patients, and the STING pathway activated by cfDNA-OLP might play a critical role in OLP pathogenesis. Treatment with PAMAM-G3 reduced the inflammation induced by cfDNA-OLP, and therefore, may be a potential treatment strategy for OLP.

Objective: The purpose of current research is to explore the function of retinoic acid-induced protein 14 (RAI14), being a reciprocal protein of carboxypeptidase N1 (CPN1), and as a biomarker for prognosis and immunoregulatory effects in breast cancers.Methods: Interacting proteins of CPN1 were characterized by co-immunoprecipitation (CO-IP) and mass spectrometry. We evaluated RAI14 expression and related clinical prognosis based on bioinformatics methods. The level of relevance between RAI14 and infiltrating immune cells biomarkers was investigated by using TIMER and certificated by immunohistochemical staining and cytology experiments.Results: RAI14 is an interacting protein of CPN1. Higher RAI14 expression in TNBC was significantly correlated with poor prognosis in TNBC, especially (RFS: HR = 1.32, p = 0.015; DFS: HR = 1.18, p = 0.035). The estrogen receptor (ER), P53 status, and histological types and triple-negative status were observed and correlated with RAI14 expression. Moreover, the level of RAI14 was positive in relation with the expression of CD163 (M2 macrophages marker, r = 0.393, p = 1.89e-06) and PD-1 (T-cell exhaustion marker, r = 0.626, p = 4.82e-03), indicating RAI14 levels were mainly related to M2 macrophages and T-cell exhaustion infiltration in TNBC. Furthermore, CPN1 overexpression was accompanied by RAI14 and PD-L1 upregulation, and a correlation was found among them.Conclusions: RAI14 is a potential downstream molecule of CPN1, which may be a potential prognostic biomarker and identification of an immunosuppressive tumor microenvironment in TNBC.

Abstract Background Overexpression of ATP‐binding cassette (ABC) transporter is a major contributor to multidrug resistance (MDR), in which cancer cells acquire resistance to a wide spectrum of chemotherapeutic drugs. In this work, we evaluated the sensitizing effect of sitravatinib, a broad‐spectrum tyrosine kinase inhibitor (TKI), on ATP‐binding cassette subfamily B member 1 (ABCB1)‐ and ATP‐binding cassette subfamily C member 10 (ABCC10)‐mediated MDR. Methods MTT assay was conducted to examine cytotoxicity and evaluate the sensitizing effect of sitravatinib at non‐toxic concentrations. Tritium‐labeled paclitaxel transportation, Western blotting, immunofluorescence analysis, and ATPase assay were carried out to elucidate the mechanism of sitravatinib‐induced chemosensitization. The in vitro findings were translated into preclinical evaluation with the establishment of xenograft models. Results Sitravatinib considerably reversed MDR mediated by ABCB1 and partially antagonized ABCC10‐mediated MDR. Our in silico docking simulation analysis indicated that sitravatinib strongly and stably bound to the transmembrane domain of ABCB1 human‐mouse chimeric model. Furthermore, sitravatinib inhibited hydrolysis of ATP and synchronously decreased the efflux function of ABCB1. Thus, sitravatinib could considerably enhance the intracellular concentration of anticancer drugs. Interestingly, no significant alterations of both expression level and localization of ABCB1 were observed. More importantly, sitravatinib could remarkably restore the antitumor activity of vincristine in ABCB1‐mediated xenograft model without observable toxic effect. Conclusions The findings in this study suggest that the combination of sitrvatinib and substrate antineoplastic drugs of ABCB1 could attenuate the MDR mediated by the overexpression of ABCB1.