Recent advances and challenges in the interaction between myofibrillar proteins and flavor substances.

Myofibrillar proteins are an important component of proteins. Flavor characteristics are the key attributes of food quality. The ability of proteins to bind flavor is one of their most fundamental functional properties. The dynamic balance of release and retention of volatile flavor compounds in protein-containing systems largely affects the sensory quality and consumer acceptability of foods. At present, research on flavor mainly focuses on the formation mechanism of flavor components, while there are few reports on the release and perception of flavor components. This review introduces the composition and structure of myofibrillar proteins, the classification of flavor substances, the physical binding and chemical adsorption of myofibrillar proteins and volatile flavor substances, as well as clarifies the regulation law of flavor substances from the viewpoint of endogenous flavor characteristics and exogenous environment factors, to provide a theoretical reference for the flavor regulation of meat products.

Heme-Mimetic Photosensitizer with Iron-Targeting and Internalizing Properties for Enhancing PDT Activity and Promoting Infected Diabetic Wound Healing.

The management of multibacterial infections remains clinically challenging in the care and treatment of chronic diabetic wounds. Photodynamic therapy (PDT) offers a promising approach to addressing bacterial infections. However, the limited target specificity and internalization properties of traditional photosensitizers (PSs) toward Gram-negative bacteria pose significant challenges to their antibacterial efficacy. In this study, we designed an iron heme-mimetic PS (MnO2@Fe-TCPP(Zn)) based on the iron dependence of bacteria that can be assimilated by bacteria and retained in different bacteria strains (Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus) and which shows high PDT antibacterial efficacy. For accelerated wound healing after antibacterial treatment, MnO2@Fe-TCPP(Zn) was loaded into a zwitterionic hydrogel with biocompatibility and antifouling properties to form a nanocomposite antibacterial hydrogel (PSB-MnO2@Fe-TCPP(Zn)). In the multibacterial infectious diabetic mouse wound model, the PSB-MnO2@Fe-TCPP(Zn) hydrogel dressing rapidly promoted skin regeneration by effectively inhibiting bacterial infections, eliminating inflammation, and promoting angiogenesis. This study provides an avenue for developing broad-spectrum antibacterial nanomaterials for combating the antibiotic resistance crisis and promoting the healing of complex bacterially infected wounds.

Identification of metabolism-related key genes as potential biomarkers for pathogenesis of immune thrombocytopenia.

Immune thrombocytopenia (ITP), an acquired autoimmune disease, is characterized by immune-mediated platelet destruction. A biomarker is a biological entity that contributes to disease pathogenesis and reflects disease activity. Metabolic alterations are reported to be associated with the occurrence of various diseases. As metabolic biomarkers for ITP have not been identified. This study aimed to identify metabolism-related differentially expressed genes as potential biomarkers for pathogenesis of ITP using bioinformatic analyses.The microarray expression data of the peripheral blood mononuclear cells were downloaded from the Gene Expression Omnibus database (GSE112278 download link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112278 ). Key module genes were intersected with metabolism-related genes to obtain the metabolism-related key candidate genes. The hub genes were screened based on the degree function in the coytoscape sofware. The key ITP-related genes were subjected to functional enrichment analysis. Immune infiltration analysis was performed using a single-sample gene set enrichment analysis algorithm to evaluate the differential infiltration levels of immune cell types between ITP patient and control. Molecular subtypes were identified based on the expression of hub genes. The expression of hub genes in the ITP patients was validated using quantitative real-time polymerase chain reaction analysis. This study identified five hub genes (ADH4, CYP7A1, CYP1A2, CYP8B1, and NR1H4), which were be associated with the pathogenesis of ITP, and two molecular subtypes of ITP. Among these hub genes, CYP7A1 and CYP8B1 involved in cholesterol metabolism,were further verified in clinical samples.

Osthole ameliorates early diabetic kidney damage by suppressing oxidative stress, inflammation and inhibiting TGF-ß1/Smads signaling pathway.

BACKGROUND: Osthole is a natural active ingredient extracted from the traditional Chinese medicine Cnidium monnieri. It has been demonstrated to have anti-inflammatory, anti-fibrotic, and anti-hyperglycemic properties. However, its effect on diabetic kidney disease (DKD) remains uncertain. This study aims to assess the preventive and therapeutic effects of osthole on DKD and investigate its underlying mechanisms. METHODS: A streptozotocin/high-fat and high-sucrose diet induced Type 2 diabetic rat model was established. Metformin served as the positive drug control. Diabetic rats were treated with metformin or three different doses of osthole for 8 weeks. Throughout the treatment period, the progression of DKD was assessed by monitoring increases in urinary protein, serum creatinine, urea nitrogen, and uric acid, along with scrutinizing kidney pathology. Enzyme-linked immunosorbent assay (ELISA) was employed to detect inflammatory factors and oxidative stress levels. At the same time, immunohistochemical staining was utilized to evaluate changes in alpha-smooth muscle actin, fibronectin, E-cadherin, and apoptosis. The alterations in TGF-ß1/Smads signaling pathway were ascertained through western blot and immunofluorescence. Furthermore, we constructed a high glucose-stimulated HBZY-1 cells model to uncover its molecular protective mechanism. RESULTS: Osthole significantly reduced fasting blood glucose, insulin resistance, serum creatinine, uric acid, blood urea nitrogen, urinary protein excretion, and glomerular mesangial matrix deposition in diabetic rats. Additionally, significant improvements were observed in inflammation, oxidative stress, apoptosis, and fibrosis levels. The increase of ROS, apoptosis and hypertrophy in HBZY-1 cells induced by high glucose was reduced by osthole. Immunofluorescence and western blot results demonstrated that osthole down-regulated the TGF-ß1/Smads signaling pathway and related protein expression. CONCLUSION: Our findings indicate that osthole exhibits potential preventive and therapeutic effects on DKD. It deserves further investigation as a promising drug for preventing and treating DKD.

Interlayer Polymerization to Construct a Fully Conjugated Covalent Organic Framework as a Metal-Free Oxygen Reduction Reaction Catalyst for Anion Exchange Membrane Fuel Cells.

Two-dimensional (2D) covalent organic frameworks (COFs) have a multilayer skeleton with a periodic π-conjugated molecular array, which can facilitate charge carrier transport within a COF layer. However, the lack of an effective charge carrier transmission pathway between 2D COF layers greatly limits their applications in electrocatalysis. Herein, by employing a side-chain polymerization strategy to form polythiophene along the nanochannels, a conjugated bridge is constructed between the COF layers. The as-synthesized fully conjugated COF (PTh-COF) exhibits high oxygen reduction reaction (ORR) activity with narrowed energy band gaps. Correspondingly, PTh-COF is tested as a metal-free cathode catalyst for anion exchange membrane fuel cells (AEMFCs) which showed a maximum power density of 176 mW cm-2 under a current density of 533 mA cm-2. The density functional theory (DFT) calculation reveals that interlayer conjugated polythiophene optimizes the electron cloud distribution, which therefore enhances the ORR performance. This work not only provides new insight into the construction of a fully conjugated covalent organic framework but also promotes the development of new metal-free ORR catalysts.

Gut bacterial and fungal dysbiosis in tuberculosis patients.

BACKGROUND: Recent studies have more focused on gut microbial alteration in tuberculosis (TB) patients. However, no detailed study on gut fungi modification has been reported till now. So, current research explores the characteristics of gut microbiota (bacteria)- and mycobiota (fungi)-dysbiosis in TB patients and also assesses the correlation between the gut microbiome and serum cytokines. It may help to screen the potential diagnostic biomarker for TB. RESULTS: The results show that the alpha diversity of the gut microbiome (including bacteria and fungi) decreased and altered the gut microbiome composition of TB patients. The bacterial genera Bacteroides and Prevotella were significantly increased, and Blautia and Bifidobacterium decreased in the TB patients group. The fungi genus Saccharomyces was increased while decreased levels of Aspergillus in TB patients. It indicates that gut microbial equilibrium between bacteria and fungi has been altered in TB patients. The fungal-to-bacterial species ratio was significantly decreased, and the bacterial-fungal trans-kingdom interactions have been reduced in TB patients. A set model including Bacteroides, Blautia, Eubacterium_hallii_group, Apiotrichum, Penicillium, and Saccharomyces may provide a better TB diagnostics option than using single bacterial or fungi sets. Also, gut microbial dysbiosis has a strong correlation with the alteration of IL-17 and IFN-γ. CONCLUSIONS: Our results demonstrate that TB patients exhibit the gut bacterial and fungal dysbiosis. In the clinics, some gut microbes may be considered as potential biomarkers for auxiliary TB diagnosis.

Integrated micro/nano drug delivery system based on magnetically responsive phase-change droplets for ultrasound theranostics.

Phase-change droplets (PCDs) are intelligent responsive micro and nanomaterials developed based on micro/nano bubbles. Subject to external energy inputs such as temperature and ultrasound, the core substance, perfluorocarbon (PFC), undergoes a phase transition from liquid to gas. This transformation precipitates alterations in the PCDs' structure, size, ultrasound imaging capabilities, drug delivery efficiency, and other pertinent characteristics. This gives them the ability to exhibit "intelligent responses". This study utilized lipids as the membrane shell material and perfluorohexane (PFH) as the core to prepare lipid phase-change droplets. Superparamagnetic nanoparticles (PEG-functionalized Fe3O4 nanoparticles) and the anti-tumor drug curcumin (Cur) were loaded into the membrane shell, forming magnetic drug-loaded phase-change droplets (Fe-Cur-NDs). These nanoscale phase-change droplets exhibited excellent magnetic resonance/ultrasound imaging capabilities and thermal/ultrasound-mediated drug release. The Fe-Cur-NDs showed excellent anti-tumor efficacy for the MCF-7 cells under low-intensity focused ultrasound (LIFU) guidance in vitro. Therefore, Fe-Cur-NDs represent a promising smart responsive theranostic integrated micro/nano drug delivery system.

Ultralow Loading Copper-Intercalated MoO3 Nanobelts with High Activity against Antibiotic-Resistant Bacteria.

In recent years, the infection rate of antibiotic resistance has been increasing year by year, and the prevalence of super bacteria has posed a great threat to human health. Therefore, there is an urgent need to find new antibiotic alternatives with long-term inhibitory activity against a broad spectrum of bacteria and microorganisms in order to avoid the proliferation of more multidrug-resistant (MDR) bacteria. The presence of natural van der Waals (vdW) gaps in layered materials allows them to be easily inserted by different guest species, providing an attractive strategy for optimizing their physicochemical properties and applications. Here, we have successfully constructed a copper-intercalated α-MoO3 nanobelt based on nanoenzymes, which is antibacterial through the synergistic effect of multiple enzymes. Compared with α-MoO3, MoO3-x/Cu nanobelts with a copper loading capacity of 2.11% possess enhanced peroxidase (POD) catalytic activity and glutathione (GSH) depletion, indicating that copper intercalation significantly improves the catalytic performance of the nanoenzymes. The MoO3-x/Cu nanobelts are effective in inducing POD and oxidase (OXD) and catalase (CAT) activities in the presence of H2O2 and O2, which resulted in the generation of large amounts of reactive oxygen species (ROS), which were effective in bacterial killing. Interestingly, MoO3-x/Cu nanobelts can serve as glutathione oxidase (GSHOx)-like nanoenzymes, which can deplete GSH in bacteria and thus significantly improve the bactericidal effect. The multienzyme-catalyzed synergistic antimicrobial strategy shows excellent antimicrobial efficiency against ß-lactamase-producing Escherichia coli (ESBL-E. coli) and methicillin-resistant Staphylococcus aureus (MRSA). MoO3-x/Cu exhibits excellent spectral bactericidal properties at very low concentrations (20 µg mL-1). Our work highlights the wide range of antibacterial and anti-infective biological applications of copper-intercalated MoO3-x/Cu nanobelt catalysts.

Small-molecule inhibitor HI-TOPK-032 improves NK-92MI cell infiltration into ovarian tumours.

The effectiveness of natural killer (NK) cells transferred adoptively in combating solid tumours is limited by challenges such as their difficulty in penetrating tumours from the bloodstream and maintaining viability without the support of interleukin-2 (IL-2). Genetically modified NK-92MI cells, which can release IL-2 to sustain their viability, have been identified as a promising alternative. This adaptation addresses the negative consequences of systemic IL-2 administration. The role of PSD-95/discs large/ZO-1 (PDZ)-binding kinase (PBK) in cancer development is recognized, but its effects on immunity are not fully understood. This study explores how PBK expression influences the ability of NK-92MI cells to infiltrate ovarian tumours. Elevated levels of PBK expression have been found in various cancers, including ovarian cancer (OV), with analyses showing higher PBK mRNA levels in tumour tissues compared to normal ones. Immunohistochemistry has confirmed increased PBK expression in OV tissues. Investigations into PBK's role in immune regulation reveal its association with immune cell infiltration, indicating a potentially compromised immune environment in OV with high PBK expression. The small-molecule inhibitor HI-TOPK-032, which inhibits PBK, enhances the cytotoxicity of NK-92MI cells toward OV cells. It increases the production of interferon-γ and tumour necrosis factor-α, reduces apoptosis and encourages cell proliferation. Mechanistic studies showed that contact with OV cells treated with HI-TOPK-032 upregulates CD107a on NK-92 cells. In vivo studies demonstrated that HI-TOPK-032 improves the antitumour effects of NK-92MI cells in OVCAR3Luc xenografts, extending survival without significant side effects. Safety assessments in mice confirm HI-TOPK-032's favourable safety profile, highlighting its potential as a viable antitumour therapy. These results suggest that combining NK-92MI cells with HI-TOPK-032 enhances antitumour effectiveness against OV, indicating a promising, safe and effective treatment strategy that warrants further clinical investigation.

Pricing strategy research in the dual-channel pharmaceutical supply chain considering service.

In the context of developing a new era, the pharmaceutical supply chain market has gradually transformed from a seller's market to a buyer's market. The closer the consumers are, the greater the market pricing power, so the pharmaceutical market power of manufacturers and retailers has also changed. This study considers the effect of service on the pricing strategy of the pharmaceutical platform supply chain. The study aimed to coordinate optimization, and the coordination strategy of the pharmaceutical platform supply chain of complementary products is discussed mainly by researching the price and service factors. Various situations are studied by hypothesis and model solving. This study uses Stackelberg game decision-making. Manufacturers are at the forefront of platform supply chain decisions. The research found that the price was lower under centralized decision-making than under decentralized decision-making. Coordination between price and service levels needs attention in the pharmaceutical platform supply chain of complementary products, and the service level should be controlled within a certain range. Only by improving the service level can enterprises maximize profits, providing a theoretical basis for pharmaceutical supply chain pricing strategy research. Supply chain members must strive to improve service levels to improve medical supply consumers' (patients) psychological satisfaction level. Service levels do not fully mitigate channel conflict. Therefore, pharmaceutical complements have become a way to alleviate the conflicts in the pharmaceutical platform supply chain.

Aerobically Autoxidized Self-Charge Concept Derived from Synergistic Pyrrolic Nitrogen and Catechol Configurations in N, O Co-Doped Carbon Cathode Material.

Aerobically autoxidized self-charging concept has drawn significant attraction due to its promising chemical charge features without external power supply. Particularly, heteroatom-doped carbon materials with abundant oxidizable sites and good conductivity are expected to be ideal cathode materials. However, there is no well-defined aerobically autoxidized self-charging concept based on heteroatom-doped carbon materials, significantly hindering the design of related carbon cathodes. An aerobically autoxidized self-chargeable concept derived from synergistic effect of pyrrolic nitrogen and catechol configuration in carbon cathode using model single pyrrolic nitrogen and oxygen (N-5, O) co-doped carbon and O-enriched carbon is proposed. First, self-charging of N-5, O co-doped carbon cathode can be achieved by aerobic oxidation of pyrrolic nitrogen and catechol to oxidized pyrrolic nitrogen and ortho-quinone configurations, respectively. Second, introducing a single pyrrolic nitrogen configuration enhanced acidic wettability of N-5, O co-doped carbon facilitating air self-charge/galvanic discharge involving proton removal/introduction. Third, synergistic effect of pyrrolic nitrogen and hydroxyl species with the strong electron-donating ability to conjugated carbon-based backbone endows N-5, O co-doped carbon with a higher highest occupied molecular orbital (HOMO) energy level more susceptible to oxidation charging. The assembled Cu/Carbon batteries can drive a timer after every air-charging run. This promising aerobically autoxidized self-charging concept can inspire exploring high-efficiency self-charging devices.

Unraveling the Physicochemical Properties and Bacterial Communities in Rabbit Meat during Chilled Storage.

The freshness and bacterial communities of fresh and salted rabbit meat during 8 days of refrigerated storage at 4 °C were evaluated. The results showed that the addition of 2% salt significantly changed the color of meat, of which the lightness (L*), redness (a*), and yellowness (b*) were lower than that of fresh meat over time. The pH of all samples increased during storage, and meat with salt addition had lower values in comparison to fresh samples over time. The total volatile base nitrogen (TVB-N) concentration increased rapidly in salt-treated meat but was significantly (p < 0.05) lower than that in meat without salt added before 6 days. Over time, the content of thiobarbituric acid reactive substances (TBARS) showed a progressive trend, but a rapid increase occurred in salted meat. High-throughput sequencing showed that the microflora of each sample had a positive trend in alpha diversity and a negative trend in beta diversity. Bacterial taxonomic analysis indicated that the initial microbial flora for chilled rabbit meat was dominated by Shigaella, Bacteroides, and Lactococcus, and the population of Brochothrix and Psychrobacter increased over time and became the dominant spoilage bacterium. In particular, the addition of salt significantly reduced the abundance of Psychrobacter and Brochothrix. These findings might provide valuable information regarding the quality monitoring of rabbit meat during chilled storage.

Effects of Saccharomyces cerevisiae and Kluyveromyces marxianus on the Physicochemical, Microbial, and Flavor Changes of Sauce Meat during Storage.

Saccharomyces cerevisiae (S. cerevisiae) and Kluyveromyces marxianus (K. marxianus) are often used as fermenters in yogurt and alcohol, and have been less studied within meat products. The yeasts were added to sauce meat, and the uninoculated group served as a control in this study to examine and compare the changing patterns of physicochemical and flavor characteristics of S. cerevisiae and K. marxianus on sauce meat during storage. The changes in moisture content, aw, pH, thiobarbituric acid reactive substances (TBARS), and other flavor characteristics were measured in sauce meat during the first, second, fourth, and sixth months after production. The following factors were examined: moisture content, aw, pH, TBARS, peroxide value (POV), acid value (AV), soluble protein (SP), free amino acid (FAA), and volatile flavoring compounds. With VIP > 1 and p < 0.05 as the screening conditions, the partial least squares model (PLS-DA) was used to assess the distinctive flavor components in the sausages. The findings demonstrated that the three groups' changes in sauce meat were comparable during the first two months of storage but differed significantly between the 4th and 6th months. The moisture content, water activity, and pH of the sauce meat decreased gradually with the storage time; TBARS, AV, and FAA increased significantly; SP decreased significantly from 2.61 to 1.72, while POV increased to 0.03 and then decreased to 0.02. The POV and TBARS values of the yeast-infected meat were substantially lower than those of the control group, and the POV and TBARS values of the meat inoculated with S. cerevisiae were particularly decreased (p < 0.05). The POV and TBARS values of SC (S. cerevisiae group) decreased by 49.09% and 40.15%, respectively, compared to CK (the control group) at the time of storage until June. The experimental group (KM: K. marxianus group) significantly increased the SP and FAA values of the sauce meat (p < 0.05) by 32.4% and 29.84% compared to the CK group, respectively. Esters and olefins as well as alcohols and esters were much greater in meat that had been supplemented with S. cerevisiae and K. marxianus than in meat from the control group. In conclusion, inoculating sauce meat with S. cerevisiae can significantly enhance the quality and flavor of sauce meat while it is being stored.

Coronary Microvascular Dysfunction and Diffuse Myocardial Fibrosis in Patients With Type 2 Diabetes Using Quantitative Perfusion MRI.

BACKGROUND: Imaging techniques that quantitatively and automatically measure changes in the myocardial microcirculation in patients with diabetes are lacking. PURPOSE: To detect diabetic myocardial microvascular complications using a novel automatic quantitative perfusion MRI technique, and to explore the relationship between myocardial microcirculation dysfunction and fibrosis. STUDY TYPE: Prospective. SUBJECTS: 101 patients with type 2 diabetes mellitus (T2DM) (53 without and 48 with complications), 20 healthy volunteers. FIELD STRENGTH/SEQUENCE: 3.0T; modified Look-Locker inversion-recovery sequence; saturation recovery sequence and dual-bolus technique; segmented fast low-angle shot sequence. ASSESSMENT: All participants underwent MRI to determine the rest myocardial blood flow (MBF), stress MBF, myocardial perfusion reserve (MPR), and extracellular volume (ECV), which represents the extent of myocardial fibrosis. STATISTICAL TESTS: Kolmogorov-Smirnov test, Shapiro-Wilk test, Kruskal-Wallis H test, Mann-Whitney U test, chi-square test, Spearman correlation coefficient, multivariable linear regression analysis. P < 0.05 was considered statistically significant. RESULTS: The rest MBF was not significantly different between the T2DM without complications group (1.1, IQR: 0.9-1.3) and the control group (1.1, 1.0-1.3) (P = 1.000), but it was significantly lower in the T2DM with complications group (0.8, 0.6-1.0) than in both other groups. The stress MBF and MPR were significantly lower in the T2DM without complications group (1.9, 1.5-2.3, and 1.7, 1.4-2.1, respectively) than in the control group (3.0, 2.6-3.5, and 2.7, 2.4-3.1, respectively), and were also significantly lower in the T2DM with complications group (1.1, 0.9-1.4, and 1.4, 1.2-1.8, respectively) than in the T2DM without complications group. A decrease in MBF and MPR were significantly associated with an increase in the ECV. DATA CONCLUSION: Quantitative perfusion MRI can evaluate myocardial microcirculation dysfunction. In T2DM, there was a significant decrease in both MBF and MPR compared to healthy controls, with the decrease being significantly different between T2DM with and without complications groups. The decrease of MBF was significantly associated with the development of myocardial fibrosis, as determined by ECV. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Single-cell RNA sequencing of cervical exfoliated cells reveals potential biomarkers and cellular pathogenesis in cervical carcinogenesis.

Cervical cancer (CC) is a common gynecological malignancy. Despite the current screening methods have been proved effectively and significantly decreased CC morbidity and mortality, deficiencies still exist. Single-cell RNA sequencing (scRNA-seq) approach can identify the complex and rare cell populations at single-cell resolution. By scRNA-seq, the heterogeneity of tumor microenvironment across cervical carcinogenesis has been mapped and described. Whether these alterations could be detected and applied to CC screening is unclear. Herein, we performed scRNA-seq of 56,173 cervical exfoliated cells from 15 samples, including normal cervix, low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and malignancy. The present study delineated the alteration of immune and epithelial cells derived during the cervical lesion progression. A subset of lipid-associated macrophage was identified as a tumor-promoting element and could serve as a biomarker for predicting the progression of LSIL into HSIL, which was then verified by immunofluorescence. Furthermore, cell-cell communication analysis indicated the SPP1-CD44 axis might exhibit a protumor interaction between epithelial cell and macrophage. In this study, we investigated the cervical multicellular ecosystem in cervical carcinogenesis and identified potential biomarkers for early detection.

Unprecedented 100% conversion from pyridinic to pyrrolic nitrogen configuration for electrochemically active nitrogen-doped carbon materials.

Nitrogen-doped carbons with promising electrochemical performance exhibit a strong dependence on nitrogen configuration. Therefore, accurate control of nitrogen configurations is crucial to clarify their influence. Unfortunately, there is still no well-defined conversion route to finely control nitrogen configuration. Herein, we proposed the concept of 100% conversion from pyridinic to pyrrolic nitrogen in carbon materials through low-temperature pyrolysis and alkali activation of hydroxypyridine-3-halophenol-formaldehyde resins. Their dehalogenation pyrolysis promotes formation of carbon intermediates and conversion of tautomeric pyridone and hydroxypyridine into pyrrolic and pyridinic nitrogen through eliminating carbonyl and hydroxyl functionalities, respectively. Continuous thermal alkali activation introduces hydroxyl groups into carbon materials, converting pyridinic species to intermediate hydroxypyridine and pyridone; subsequently, these configurations transform to pyridinic and pyrrolic nitrogen, respectively, and finally, an excessive alkali ensures 100% conversion from pyridinic to pyrrolic nitrogen. NaOH activation for pyrrolic and pyridinic nitrogen co-doped carbon and KOH activation for model nitrogen-containing compounds including acridine, phenanthridine, and acridone further confirm that alkali activation plays an indispensable role in 100% conversion from pyridinic to pyrrolic units through the tautomeric hydroxypyridine and pyridone intermediates. Low-temperature alkali-induced controllable conversion of nitrogen configuration in carbon materials is suitable modulating nitrogen configurations for almost all nitrogen-doped carbon materials in electrochemical applications.

Vemurafenib induces senescence in acute myeloid leukemia and myelodysplastic syndrome by activating the HIPPO signaling pathway: implications for potential targeted therapy.

BACKGROUND: The outcome of Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remain dismal despite the development of treatment. Targeted therapy is gaining more and more attention in improving prognosis. METHODS: Expression of BRAF was analyzed by RT-qPCR in AML and MDS patients. Cells viability treated by drugs was measured by CCK-8 assay. Network pharmacology and RNA-sequence were used to analyze the mechanism of drugs and verified in vitro and xenograft tumor model. RESULTS: Here we showed that BRAF was overexpressed in AML and MDS patients, and correlated with poor prognosis. The BRAF inhibitor-Vemurafenib (VEM) could significantly induce senescence, proliferation inhibition and apoptosis in AML cells, which can be enhanced by Bortezomib (BOR). This inhibitory effect was also verified in CD34 + cells derived from AML patients. Mechanistically, we showed that VEM combined with BOR could turn on HIPPO signaling pathway, thereby inducing cellular senescence in AML cells and xenograft mouse. CONCLUSIONS: Taken together, our findings demonstrate a significant upregulation of BRAF expression in AML and MDS patients, which is associated with unfavorable clinical outcomes. We also discovered that the BRAF inhibitor Vemurafenib induces cellular senescence through activation of the HIPPO signaling pathway. Analysis of BRAF expression holds promise as a prognostic indicator and potential therapeutic target for individuals with AML and MDS.

LeGO-LOAM-FN: An Improved Simultaneous Localization and Mapping Method Fusing LeGO-LOAM, Faster_GICP and NDT in Complex Orchard Environments.

To solve the problem of cumulative errors when robots build maps in complex orchard environments due to their large scene size, similar features, and unstable motion, this study proposes a loopback registration algorithm based on the fusion of Faster Generalized Iterative Closest Point (Faster_GICP) and Normal Distributions Transform (NDT). First, the algorithm creates a K-Dimensional tree (KD-Tree) structure to eliminate the dynamic obstacle point clouds. Then, the method uses a two-step point filter to reduce the number of feature points of the current frame used for matching and the number of data used for optimization. It also calculates the matching degree of normal distribution probability by meshing the point cloud, and optimizes the precision registration using the Hessian matrix method. In the complex orchard environment with multiple loopback events, the root mean square error and standard deviation of the trajectory of the LeGO-LOAM-FN algorithm are 0.45 m and 0.26 m which are 67% and 73% higher than those of the loopback registration algorithm in the Lightweight and Ground-Optimized LiDAR Odometry and Mapping on Variable Terrain (LeGO-LOAM), respectively. The study proves that this method effectively reduces the influence of the cumulative error, and provides technical support for intelligent operation in the orchard environment.

MR imaging findings of stage I intravenous leiomyomatosis: a retrospective single-center study in 19 cases.

OBJECTIVES: The aim was to explore the magnetic resonance imaging (MRI) features of stage-I intravenous leiomyomatosis (IVL). MATERIALS AND METHODS: From January 2019 to January 2023, clinical, pathological, and MRI data were collected from 19 cases confirmed by surgical pathology. Two radiologists retrospectively measured the tumor sizes, T1WIs, T2WIs, and ADC values and evaluated contrast-enhanced T1WIs, DWIs, complications and parauterine infiltrations. The number of tumor cells and the total nuclear area were measured. The percentage of tumor cell area out of the total area was used as the tumor cell density. RESULTS: Nineteen patients with stage-I IVL aged 33 to 66 years (mean age: 46 ± 7.6 years) were included in this study. All 19 cases were located in the myometrium or parametrium, with a mean diameter of 11.2 ± 4.8 cm. Among these cases, 14 (73.6%) were associated with leiomyoma, and six (31.6%) involved the broad ligament. Isointensity was observed in the T1WIs of 12 cases (63.2%), while slight hypointensity was seen in five patients (26.3%). Isointensity was observed in the on T2WIs of four cases (21.1%), and iso- or slight hyperintensity was observed in 15 cases (78.9%). A significant difference was detected between the normalized T2WIs of IVL and myometrium (p < 0.001). A Pearson correlation test showed demonstrated a negative correlation between the ADC and tumor cell density values (r = - 0.946, p < 0.001). Tortuous vessels were present in 17 cases (89.5%) within or next to the lesions, and multiple winding cord-like filling defects were seen in 11 cases (57.9%) within the tortuous vessels on the T2WIs. CONCLUSION: Identifying the characteristic MRI features of stage-I IVL helped improve the diagnostic accuracy achieves for this rare tumor. Stage-I IVL often presents as a large mass accompanied by leiomyoma, and it easily invades the broad ligament. TIWI signals exhibited isointensity, and T2WI signals contained iso- or slight hyperintensity. Tortuous vessels were present within or next to the lesions, and multiple winding cord-like filling defects were observed within the tortuous vessels on the T2WIs.

Chitin microspheres: From fabrication to applications.

Chitin microspheres (CMs) have attracted increasing attention due to their biocompatibility, uniform size and shape, large surface area, and porous structure. Considerable research efforts have been focused on developing CMs and promoting their applications in various areas. In this context, this review aims to describe the most recent progress in the fabrication and application of CMs. Different routes that can be used to prepare CMs, such as the drip method and the emulsion method, are emphatically introduced. Moreover, the applications of CMs as drug delivery systems, wound dressings, three-dimensional (3D) scaffolds, water purification, and functional supporting materials in the fields of biomedicine, tissue engineering, environmental protection, and energy storage are also highlighted. We hope this review can provide a comprehensive and useful database for further innovation of CMs.