Alantolactone attenuates high-fat diet-induced inflammation and oxidative stress in non-alcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a chronic disease with an increasing incidence, which can further develop into liver fibrosis and hepatocellular carcinoma at the end stage. Alantolactone (Ala), a sesquiterpene lactone isolated from Asteraceae, has shown anti-inflammatory effects in different models. However, the therapeutic effect of Ala on NAFLD is not clear. METHODS: C57BL/6 mice were fed a high-fat diet (HFD) to induce NAFLD. After 16 weeks, Ala was administered by gavage to observe its effect on NAFLD. RNA sequencing of liver tissues was performed to investigate the mechanism. In vitro, mouse cell line AML-12 was pretreated with Ala to resist palmitic acid (PA)-induced inflammation, oxidative stress and fibrosis. RESULTS: Ala significantly inhibited inflammation, fibrosis and oxidative stress in HFD-induced mice, as well as PA-induced AML-12 cells. Mechanistic studies showed that the effect of Ala was related to the induction of Nrf2 and the inhibition of NF-κB. Taken together, these findings suggested that Ala exerted a liver protective effect on NAFLD by blocking inflammation and oxidative stress. CONCLUSIONS: The study found that Ala exerted a liver protective effect on NAFLD by blocking inflammation and oxidative stress, suggesting that Ala is an effective therapy for NAFLD.

First report of Diaporthe eres causing leaf spot on Rosa roxburghii Tratt in Guizhou Province, China.

Rosa roxburghii Tratt is a plant from the Rosaceae family whose fruits are rich in vitamins, dietary fiber, flavonoids, phenolic acids, and other active components (Jiang, et al. 2024). In July 2023, about R. roxburghii 500 plants were investigated in a field of 6000 m2 in Guiding County (107°14'E, 26°45'N), Guizhou province, China, and the results showed a leaf spot incidence of s 20 to 30%. . The affected leaves had irregular, black lesions with a clear blackish brown boundary and faint black conidiomata in a brown center. Fifteen symptomatic leaves were collected from 10 plants washed with sterile distilled water, and 5 × 5 mm pieces of the infected tissues were cut. After surface sterilization for30 s with 75% ethanol, 2 min with 3% NaOCl, three washes in sterilized distilled water, the leaf pieces were dried and placed on potato dextrose agar (PDA) and incubated at 25℃ for 5 days. Three isolates (H3-Y-1-1, H3-Y-1-2, H3-Y-1-3) with identical morphology were obtained, and the isolate H3-Y-1-1was selected for further study. The colonies on PDA exhibited irregular growth patterns, with white felty aerial mycelium on the upper surface, and white mycelium on the lower surface. Conidiomata were irregularly distributed over the agar surface. The isolate H3-Y-1-1 produced darkly pigmented pycnidia on PDA after 30 days and oozed milky mucilaginous drops. The fungus produced two types of conidia, α and ß. Regular α conidia were 4.74 - 5.96 × 1.52 - 2.24 µm (n = 50), hyaline, elongated, biguttulate and non-septate. Beta conidia were 20.13 - 25.74 × 0.86 - 1.29 µm (n = 50), aseptate, hyaline, smooth, spindle shaped, slightly curved to bent. The morphological features were consistent with the description of Diaporthe eres (Pereira, et al. 2022). The pathogen was confirmed to be D. eres by amplification and sequencing of the internal transcribed spacer region (ITS), the partial ß-tubulin (TUB), the partial translation elongation factor 1-alpha (TEF) genes using primers ITS1/ITS4, Bt-2a/Bt-2b, EF1-728F/EF1-986R, respectively. Sequences from PCR amplification were deposited in GenBank with accession numbers PP411998 (ITS), PP502153 (TUB), PP502156 (TEF). BLAST searches of the sequences revealed (96%) (500/523nt), 97% (479/494 nt) and 99% (334/338 nt) homology with those of D. eres CBS 138594 from GenBank (OM698848, OM752196 and OM752197), respectively. Phylogenetic analysis using maximum-likelihood and Bayesian methods placed the isolate H3-Y-1-1 in a well-supported cluster with D. eres CBS 101742. The pathogen was thus identified as D. eres based on the morphological characterization and molecular analyses (Feng, et al. 2013; Tao, et al. 2020). To assess its pathogenicity, healthy R. roxburghii potted plants were inoculated with H3-Y-1-1 spore suspensions. Symptomatic leaves mirroring field symptoms were observed after XX days of incubations at XX°C, while control plants exhibited no symptoms. Diaporthe eres was consistently reisolated from the infected leaves showing brown irregular or round lesions at the initial stage of the disease, expanding and become more irregular over time ultimately causing leaf curling and plant death. To our knowledge, this is the first report of leaf spot on R. roxburghii caused by D. eres in China. The disease may become a serious threat to fruit of R. roxburghii production in China. Therefore, detection of this pathogen is very important to ensure timely disease management.

Origin of the light-induced spin currents in heavy metal/magnetic insulator bilayers.

Light-induced spin currents with the faster response is essential for the more efficient information transmission and processing. Herein, we systematically explore the effect of light illumination energy and direction on the light-induced spin currents in the W/Y3Fe5O12 heterojunction. Light-induced spin currents can be clearly categorized into two types. One is excited by the low light intensity, which mainly involves the photo-generated spin current from spin photovoltaic effect. The other is caused by the high light intensity, which is the light-thermally induced spin current and mainly excited by spin Seebeck effect. Under low light-intensity illumination, light-thermally induced temperature gradient is very small so that spin Seebeck effect can be neglected. Furthermore, the mechanism on spin photovoltaic effect is fully elucidated, where the photo-generated spin current in Y3Fe5O12 mainly originates from the process of spin precession induced by photons. These findings provide some deep insights into the origin of light-induced spin current.

Hepatitis B virus X protein promotes tumor glycolysis by downregulating lncRNA OIP5-AS1/HKDC1 in HCC.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide, with Hepatitis B virus (HBV) infection being the leading cause. This study aims to investigate the role of HBV in HCC pathogenesis involving glucose metabolism. Long non-coding RNA (lncRNA) OIP5-AS1 was significantly downregulated in HBV-positive HCC patients, and its low expression indicated a poor prognosis. This lncRNA was primarily localized in the cytoplasm, acting as a tumor suppressor. HBV protein X (HBx) repressed OIP5-AS1 expression by inhibiting a ligand-activated transcriptional factor peroxisome proliferator-activated receptor α (PPARα). Furthermore, mechanistic studies revealed that OIP5-AS1 inhibited tumor growth by suppressing Hexokinase domain component 1 (HKDC1)-mediated glycolysis. The expression of HKDC1 could be enhanced by transcriptional factor sterol regulatory element-binding protein 1 (SREBP1). OIP5-AS1 facilitated the ubiquitination and degradation of SREBP1 to suppress HKDC1 transcription, which inhibited glycolysis. The results suggest that lncRNA OIP5-AS1 plays an anti-oncogenic role in HBV-positive HCC via the HBx/OIP5-AS1/HKDC1 axis, providing a promising diagnostic marker and therapeutic target for HBV-positive HCC patients.

A Comparative Study of Two Radiomics-Based Blood Flow Modes with Thyroid Imaging Reporting and Data System in Predicting Malignancy of Thyroid Nodules and Reducing Unnecessary Fine-Needle Aspiration Rate.

RATIONALE AND OBJECTIVES: We aimed to compare superb microvascular imaging (SMI)-based radiomics methods, and contrast-enhanced ultrasound (CEUS)-based radiomics methods to the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for classifying thyroid nodules (TNs) and reducing unnecessary fine-needle aspiration biopsy (FNAB) rate. MATERIALS AND METHODS: This retrospective study enrolled a dataset of 472 pathologically confirmed TNs. Radiomics characteristics were extracted from B-mode ultrasound (BMUS), SMI, and CEUS images, respectively. After eliminating redundant features, four radiomics scores (Rad-scores) were constructed. Using multivariable logistic regression analysis, four radiomics prediction models incorporating Rad-score and corresponding US features were constructed and validated in terms of discrimination, calibration, decision curve analysis, and unnecessary FNAB rate. RESULTS: The diagnostic performance of the BMUS + SMI radiomics method was better than ACR TI-RADS (area under the curve [AUC]: 0.875 vs. 0.689 for the training cohort, 0.879 vs. 0.728 for the validation cohort) (P < 0.05), and comparable with BMUS + CEUS radiomics method (AUC: 0.875 vs. 0.878 for the training cohort, 0.879 vs. 0.865 for the validation cohort) (P > 0.05). Decision curve analysis showed that the BMUS+SMI radiomics method could achieve higher net benefits than the BMUS radiomics method and ACR TI-RADS when the threshold probability was between 0.13 and 0.88 in the entire cohort. When applying the BMUS+SMI radiomics method, the unnecessary FNAB rate reduced from 43.4% to 13.9% in the training cohort and from 45.6% to 18.0% in the validation cohorts in comparison to ACR TI-RADS. CONCLUSION: The dual-modal SMI-based radiomics method is convenient and economical and can be an alternative to the dual-modal CEUS-based radiomics method in helping radiologists select the optimal clinical strategy for TN management.

First Report of Nigrospora sphaerica causing Leaf Spot on Rhododendron simsii in China.

Rhododendron simsii (indoor azalea) is widely cultivated for its high ornamental value (Xu et al. 2021). In April to May 2023, a leaf spot disease occurred in a field study at the Baili Azalea Forest Area (27°12'N, 105°48'E), Guizhou Province, China. About 500 plants were investigated, and the results showed that the incidence of leaf spot was 20 ~ 30%. To study this disease, 10 plants showing severe symptoms were collected. Initially, the symptoms were round or irregularly shaped brown spots (1 to 10 mm). With time, the spots enlarged and merged. Symptomatic leaves were washed with sterile distilled water, and 5 × 5 mm pieces of the infected tissues were removed. After surface sterilization (30 s with 75% ethanol, 2 min with 3% NaOCl, then washed three times with sterilized distilled water), the leaf pieces were dried and placed on potato dextrose agar (PDA) and incubated at 25℃ for 5 days. Fungal colonies developed from leaf tissues, and the germinated spores were transferred onto PDA for further purification and morphological observation. Three isolates (GUBJ23, GUBJ24, and GUBJ12) with similar morphology were obtained from five affected leaves. The representative strain GUBJ23 was selected for further study. On PDA the mycelium was initially white but with sporulation turned gray and then black. Black, single-celled conidia, spherical to sub-spherical, from 11.80 to 21.39 × 13.38 to 21.83 µm (n = 50) in diameter were borne singly on hyaline vesicles at the tips of conidiophores. These morphological characteristics were similar to those of Nigrospora sphaerica (Wang et al. 2017). To confirm the identification, primer pairs for the internal transcribed spacer (ITS) region (ITS5/ITS4), ß-tubulin (TUB2) (Bt-2a/Bt-2b), and the translation elongation factor 1-alpha (TEF1-α) (EF1-728F/EF1-986R), were used for PCR amplification of DNA from strain GUBJ23 (Carbone and Kohn 1999; Glass et al. 1995; White et al. 1990). The resulting sequences were deposited in GenBank with accession numbers OR818025 (ITS), OR835150 (TUB2), and OR835147 (TEF1-α). BLAST searches of the sequences revealed 99.80% identity (503/504 bp) of the ITS sequence, 100.00% identity (395/395 bp) of the TUB2 sequence, and 100.00% identity of the TEF1-α sequence (241/241 bp) with N. sphaerica LC7294 (accessions KX985932, KY019602, and KY019397, respectively.) Based on a combined dataset of ITS, TEF1-α, and TUB2 sequences, a phylogenetic tree was constructed using the maximum likelihood method and confirmed that isolates GUBJ23, GUBJ24, and GUBJ12 were N. sphaerica (Wang et al. 2017). Leaves of three healthy R. simsii plants were spray-inoculated with a spore suspension (105 conidia/mL), and an additional three plants were sprayed with sterile water. These plants were incubated at 25℃ in 75% relative humidity. After 5 to 7 days of inoculation, 0.5 to 1.8 mm spots appeared on the leaves. At 10 to 14 days after inoculation, grayish brown, semicircular or irregular lesions appeared on the leaves, usually with a diameter of 0.8 to 3 mm. The symptoms were like symptoms seen on naturally infected leaves, while the control leaves remained asymptomatic. The pathogen was re-isolated from diseased leaves and identified by morphological characterization and molecular analyses (ITS, TUB and TEF1-α), and the reisolated pathogen was identical to N. sphaerica. Thus completing Koch's postulates. According to previous research, N. sphaerica is a widely distributed phytopathogenic fungus that has a wide host range (Wang et al. 2017). This study is the first to identify N. sphaerica as the cause of leaf spot disease in R. simsii. Given the popularity of R. simsii as a pot plant and landscape shrub in Asia and othr regions, the occurrence of leaf spot disease seriously affects its ornamental and economic value. Therefore, it is crucial to establish and implement effective disease management practices to reduce impact of the disease.

Costunolide attenuates high-fat diet-induced inflammation and oxidative stress in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a progressive disease that can further evolve towards liver fibrosis and hepatocellular carcinoma in the end stage. Costunolide (Cos) is a natural sesquiterpene lactone that exhibits both anti-inflammatory and antioxidant properties. However, the therapeutic effect of Cos on NAFLD is not clear. In this study, we explored the potential protective effect and mechanism of Cos on NAFLD. C57BL/6 mice were fed with high-fat diet (HFD) to induce NAFLD. Cos was administered by gavage to observe the effect of Cos on NAFLD. We demonstrated that oral administration of Cos reduced HFD-induced hepatic fibrosis and the release of inflammatory cytokines, limiting the generation of reactive oxygen species. In vitro experiments revealed that pretreatment with Cos significantly decreased PA-induced production of inflammatory cytokines and fibrosis in AML-12 cells. Mechanism study showed that the effect of Cos was correlated to the induction of Nrf-2 and inhibition of NF-κB pathways. Collectively, these findings indicated that Cos exerts hepatoprotective effect against NAFLD through blocking inflammation and oxidative stress. Our study suggested that Cos might be an effective pharmacotherapy for the treatment of NAFLD.

Malignant cell receptor-ligand subtypes guide the prediction of prognosis and personalized immunotherapy of liver cancer.

OBJECTIVE: Liver cancer is a prevalent disease with a dismal prognosis. The aim of the research is to identify subgroups based on malignant cell receptor ligand gene from single-cell RNA, which might lead to customized immunotherapy for patients with liver cancer. METHODS: Based on scRNA-seq data, we identified the receptor-ligand genes associated with prognosis and classify patients into molecular subtypes by univariate Cox regression and consensus clustering. LASSO regression was performed to construct a prognostic model, which was validated in TCGA and ICGC datasets. Immune infiltration and prediction of immunotherapy response were analyzed using ssGSEA, ESTIMATE, TIDE, and TRS score calculation. Finally, qPCR and Western blot validation of key genes and protein levels in cell lines. RESULTS: A risk model using 16-gene expression levels predicted liver cancer patients' prognosis. The RiskScore associated significantly with tumor clinical characteristics and immunity, integrated with clinicopathological features for survival prediction. Differential expression of SRXN1 was verified in hepatocellular carcinoma and normal liver cells. CONCLUSION: Our study utilizes single-cell analysis to investigate the communication between malignant cells and other cell types, identifying molecular subtypes based on malignant cell receptor ligand genes, offering new insights for the development of personalized immunotherapy and prognostic prediction models.

Dual-modal radiomics nomogram based on contrast-enhanced ultrasound to improve differential diagnostic accuracy and reduce unnecessary biopsy rate in ACR TI-RADS 4-5 thyroid nodules.

BACKGROUND: American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS, TR) 4 and 5 thyroid nodules (TNs) demonstrate much more complicated and overlapping risk characteristics than TR1-3 and have a rather wide range of malignancy possibilities (> 5%), which may cause overdiagnosis or misdiagnosis. This study was designed to establish and validate a dual-modal ultrasound (US) radiomics nomogram integrating B-mode ultrasound (BMUS) and contrast-enhanced ultrasound (CEUS) imaging to improve differential diagnostic accuracy and reduce unnecessary fine needle aspiration biopsy (FNAB) rates in TR 4-5 TNs. METHODS: A retrospective dataset of 312 pathologically confirmed TR4-5 TNs from 269 patients was collected for our study. Data were randomly divided into a training dataset of 219 TNs and a validation dataset of 93 TNs. Radiomics characteristics were derived from the BMUS and CEUS images. After feature reduction, the BMUS and CEUS radiomics scores (Rad-score) were built. A multivariate logistic regression analysis was conducted incorporating both Rad-scores and clinical/US data, and a radiomics nomogram was subsequently developed. The performance of the radiomics nomogram was evaluated using calibration, discrimination, and clinical usefulness, and the unnecessary FNAB rate was also calculated. RESULTS: BMUS Rad-score, CEUS Rad-score, age, shape, margin, and enhancement direction were significant independent predictors associated with malignant TR4-5 TNs. The radiomics nomogram involving the six variables exhibited excellent calibration and discrimination in the training and validation cohorts, with an AUC of 0.873 (95% CI, 0.821-0.925) and 0.851 (95% CI, 0.764-0.938), respectively. The marked improvements in the net reclassification index and integrated discriminatory improvement suggested that the BMUS and CEUS Rad-scores could be valuable indicators for distinguishing benign from malignant TR4-5 TNs. Decision curve analysis demonstrated that our developed radiomics nomogram was an instrumental tool for clinical decision-making. Using the radiomics nomogram, the unnecessary FNAB rate decreased from 35.3 to 14.5% in the training cohort and from 41.5 to 17.7% in the validation cohorts compared with ACR TI-RADS. CONCLUSION: The dual-modal US radiomics nomogram revealed superior discrimination accuracy and considerably decreased unnecessary FNAB rates in benign and malignant TR4-5 TNs. It could guide further examination or treatment options.

Bronchiole adenoma/pulmonary ciliated mucinous nodular papillary tumor: Case series and literature review.

OBJECTIVE: To analyze the clinical-pathological characteristics of 3 cases of bronchiolar adenoma/pulmonary ciliary mucinous nodular papillary tumors, and to improve the understanding of bronchiolar adenoma (BA)/ciliated muconodular papillary tumors (CMPT) (bronchiolar adenoma/ciliated muconodular papillary tumor). METHODS: Retrospective analysis was done on the clinical information, diagnosis, and treatment of 3 instances of BA/CMPT at the Second People's Hospital of Weifang City. By scanning the CNKI, Wanfang, VIP database, and Pubmed database using the English key words "bronchiolar adenoma, ciliated muconodular papillary tumor," respectively patients with comprehensive clinical data were gathered, and studies from January 2002 to August 2021 that were relevant to the patients were examined. RESULTS: A total of 35 articles and 71 instances were found, including 3 cases in our hospital, for a total of 74 cases. There were 31 males and 43 females among them, ranging in age from 18 to 84 years (average 63 years), and 15 cases had a smoking history. The majority of them were discovered by physical examination and had no clinical symptoms. The majority of the imaging revealed solid nodules with variable forms, with some ground-glass nodules displaying vacuole and bronchial inflation signs. BA/CMPT are generally gray-white, gray-brown solid nodules with obvious boundaries but no envelope with a maximum dimension of 4 to 45 mm (average 10.6 mm) on gross examination. Acinar, papillary, and lepidic formations can be seen under the microscope at high magnification; the majority of these structures are made up of tripartite epithelial components, including basal cells, mucous cells, ciliated columnar cells, and alveolar epithelial cells, demonstrating a variety of combinations. An important basis for diagnosis in immunohistochemistry is the continuous positive basal cell layer that is shown by p63, p40, and CK5/6. BRAF and epidermal growth factor receptor are the genes that are most frequently mutated. All of the patients showed no signs of metastasis or recurrence during follow-up period. CONCLUSION: BA/CMPT is a rare benign tumor of lung epithelium. Because imaging and intraoperative cryosection diagnosis are easy to be misdiagnosed as malignant, it is necessary to further improve understanding and improve immunohistochemistry and genetic examination.

The roles of lipoxygenases and autoxidation during mackerel (Scomberomorus niphonius) dry-cured processing.

The roles of enzymatic (Lipoxygenases, LOX) oxidation and autoxidation in the dry-cured processing of mackerel were investigated by adding exogenous substances in this study. Four groups, namely control, chlorogenic acid (inhibiting LOX activity), EDTA-2Na (inhibiting autoxidation), and exogenous LOX (adding eLOX), were assigned. The results showed that lipid oxidation of mackerel was reduced by inhibiting LOX activity and autoxidation, while adding eLOX promoted lipid oxidation. Inhibition of LOX activity and autoxidation suppressed fatty acid accumulation mainly in the air-drying and curing stage, respectively. The total contents of key flavors in the mackerel during dry-cured processing were decreased by inhibiting LOX activity and autoxidation, and the former inhibitory effect was stronger than autoxidation, while it was corresponding increased through adding eLOX, of particular in the later stage of air-drying. Collectively, LOX could promote the flavor formation of the mackerel in the dry-cured processing, which could be applied in the flavor adjustment of aquatic products or some similar fields.

A Numerical Study of ITZ Percolation in Polyphase Concrete Systems Considering the Synergetic Effect of Aggregate Shape- and Size-Diversities.

The percolation of the interfacial transition zone (ITZ) is generally regarded as an important factor that may accelerate the penetration of aggressive agents in concrete materials, and its threshold is largely determined by the features of aggregates. In most numerical studies about ITZ percolation, both fine aggregates and coarse aggregates are assumed to be the particles of uniform shape, and their size distributions are generally strung together by a single function, which is quite different from reality. To quantify the ITZ percolation associated with the polydispersity of aggregate shapes and size gradations in a more realistic way, the two-dimensional (2D) meso-scale model of concrete is generated by simplifying coarse aggregates and fine aggregates as polygons and ovals, respectively. Moreover, the size gradations of them are also represented by two separate expressions. By combining these models with percolation theory, the percolation of ITZ in the 2D case is explicitly simulated, and the influence of aggregate shape- and size-diversities on the critical threshold ϕagg,c is studied in detail. Based on the simulated results of ϕagg,c, an empirically analytical expression is further proposed to fast predict the ITZ percolation, and its reliability is verified. The results show that the ITZ thickness, average aggregate fineness, coarse aggregate shape, and fine aggregate shapes are the four main contributing factors to the ITZ percolation. Compared with the existing literature, the proposed model here has a broader range of applications (e.g., mortar, concrete, and other granular systems) in the 2D case and can provide the larger predicted results, which may be closer to reality.

miR-135a inhibits the proliferation of HBV-infected hepatocellular carcinoma cells by targeting HOXA10.

Background: The incidence of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) is extremely high. MicroRNAs (miRNAs) are a type of endogenous non-coding small RNA with novel molecular therapeutic mechanisms that plays an important role in the occurrence and development of cancers. This study aimed to explore the regulation mechanism of miR-135a and HOXA10 in the proliferation, invasion, and apoptosis of HCC cells. Methods: Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was used to detect the expression level of miR-135a. Overexpression of miR-135a was used to measure the roles of miR-135a in the proliferation, invasion, and apoptosis of HCC cells. A dual luciferase experiment was performed to assess the relationship between HOXA10 and miR-135a. Western blot was applied to observe the protein levels of p-p38, p-ERK, and p-JNK. Results: The expression levels of miR-135a were significantly decreased in HCC tissues and cells. Overexpression of miR-135a inhibited the proliferation and invasion but promoted the apoptosis of HCC cells. Importantly, our results confirmed that HOXA10 was a direct target of miR-135a. Under HBV infection, silencing of HOXA10 significantly blocked the proliferation and invasion and promoted the apoptosis of HCC cells. In addition, miR-135a/HOXA10 regulated the expressions of p-p38, p-ERK, and p-JNK through the miR-135a/HOXA10 axis, thereby inhibiting the activation of the MAPK pathway. Conclusions: HBV promoted the proliferation and invasion, and inhibited the apoptosis of HCC cells by regulating the miR-135a/HOXA10 pathway. These findings provide a theoretical basis for improving the treatment of HBV-infected HCC patients.

The dynamic changes of flavors and UPLC-Q-Exactive-Orbitrap-MS based lipidomics in mackerel (Scomberomorus niphonius) during dry-cured processing.

Dry-cured mackerel is favored by consumers for its suitable salty flavor. Herein, the dynamic changes of volatile compounds and lipids in the mackerel, and the lipidomics based on UPLC-Orbitrap/MS technique during dry-cured processing were investigated. The results showed that endogenous lipases activities in dry-cured mackerel decreased. The dry-cured processing of mackerel had significant effects on its lipid classes and content. The contents of Arachidonic acid (C20:4n6), docosapentaenoic acid (C22:5n3), linoleic acid (LA, C18:2n6), alpha-linolenic acid (C18:3n3), eicosatrienoic acid (C20:3n3) and docosahexaenoic acid (DHA, C22:6n3) increased during dry-cured processing. A total of 38 kinds of volatile compounds were detected in the dry-cured mackerel, 12 of which were derived from fatty acid oxidation. Among 30 lipid metabolites (FC ≥ 2 and VIP > 2), phosphatidylethanolamine (PE, 19:0/22:6) accounted for the highest content, and its difference between three stages was the most obvious. Glycerophospholipid and sphingolipid metabolisms were the most important metabolic pathways involved in dry-cured processing.

Temperature- and pH-responsive injectable chitosan hydrogels loaded with doxorubicin and curcumin as long-lasting release platforms for the treatment of solid tumors.

The efficacy of treating solid tumors with chemotherapy is primarily hindered by dose-limiting toxicity due to off-target effects and the heterogeneous drug distribution caused by the dense extracellular matrix. The enhanced permeability and retention (EPR) effect within tumors restricts the circulation and diffusion of drugs. To overcome these obstacles, hydrogels formed in situ at the tumor site have been proposed to promote drug accumulation, retention, and long-lasting release. We developed a thiolated chitosan (CSSH) hydrogel with a gelation point of 37°C. Due to the pH-sensitive characteristics of disulfides, the prepared hydrogel facilitated drug release in the acidic tumor environment. A drug release system composed of hydrophilic doxorubicin (Dox) and hydrophobic liposome-encapsulated curcumin (Cur-Lip) was designed to enhance the long-lasting therapeutic impacts and reduce adverse side effects. These composite gels possess a suitable gelation time of approximately 8-12 min under physiological conditions. The cumulative release ratio was higher at pH = 5.5 than at pH = 7.4 over the first 24 h, during which approximately 10% of the Dox was released, and Cur was released slowly over the following 24-120 h. Cell assays indicated that the Cur-Lip/Dox/CSSH gels effectively inhibited the growth of cancer cells. These in situ-formed Cur-Lip/Dox gels with long-term drug release capabilities have potential applications for tumor suppression and tissue regeneration after surgical tumor resection.

Lactobacillus plantarum ST-III culture supernatant ameliorates alcohol-induced cognitive dysfunction by reducing endoplasmic reticulum stress and oxidative stress.

Background: Long-term alcohol exposure is associated with oxidative stress, endoplasmic reticulum (ER) stress, and neuroinflammation, which may impair cognitive function. Probiotics supplements can significantly improve cognitive function in neurodegenerative diseases such as Alzheimer's disease. Nevertheless, the effect of Lactobacillus plantarum ST-III culture supernatant (LP-cs) on alcohol-induced cognitive dysfunction remains unclear. Methods: A mouse model of cognitive dysfunction was established by intraperitoneal injection of alcohol (2 g/kg body weight) for 28 days. Mice were pre-treated with LP-cs, and cognitive function was evaluated using the Morris water maze test. Hippocampal tissues were collected for biochemical and molecular analysis. Results: LP-cs significantly ameliorated alcohol-induced decline in learning and memory function and hippocampal morphology changes, neuronal apoptosis, and synaptic dysfunction. A mechanistic study showed that alcohol activated protein kinase R-like endoplasmic reticulum kinase (PERK) signaling and suppressed brain derived neurotrophic factor (BDNF) levels via ER stress in the hippocampus, which LP-cs reversed. Alcohol activated oxidative stress and inflammation responses in the hippocampus, which LP-cs reversed. Conclusion: LP-cs significantly ameliorated alcohol-induced cognitive dysfunction and cellular stress. LP-cs might serve as an effective treatment for alcohol-induced cognitive dysfunction.

Heme induces inflammatory injury by directly binding to the complex of myeloid differentiation protein 2 and toll-like receptor 4.

Heme, as an essential component of hemoproteins, is a prosthetic co-factor found in many cells, which is essential for physiologically vital oxygen transport. However, extracellular or circulatory heme is cytotoxic and triggers inflammation. Although the proinflammatory role of heme has been reported to be associated with Toll-like receptor 4 (TLR4) signaling, the exact mechanism remains unknown. Here, we show that heme promotes TLR4 signaling and inflammation via directly physically interacting with TLR4 and its adaptor protein myeloid differentiation protein 2 (MD2). Genetic loss of MD2 ameliorates heme-induced inflammation and inflammatory cytokine production in the spleen of MD2 knockout (MD2-/-) mice. Using mouse macrophage RAW 264.7 cell line, we show that heme induces TLR4 dimerization and MD2/TLR4/MyD88 activation by physically interacting with TLR4 and MD2 in vitro. Genetic loss of MD2 inhibits heme-induced inflammation and MAPK/NF-κB pathway in mouse primary macrophages extracted from MD2-/- mice. Furthermore, pharmacological inhibition of MD2 by L6H9 ameliorates heme-induced inflammation in macrophages. These findings demonstrate that heme causes inflammation by directly binding to MD2/TLR4 complex, leading to activation of TLR4/MAPK/NF-κB signaling pathway and production of downstream effectors of inflammation.

HBV Promotes the Proliferation of Liver Cancer Cells through the hsa_circ_0000847/miR-135a Pathway.

Hepatocellular carcinoma (HCC) is currently one of the most common tumors, with a high morbidity and mortality rate. HCC induced by persistent hepatitis B virus (HBV) infection is the most common liver cancer subtype at present, and HBV-related HCC is highly malignant and its development mechanism still needs to be explored in depth. This study aimed to explore the molecular mechanism of hsa_circ_0000847 targeting miR-135a-5p (miR-135a) to regulate the proliferation, invasion, and apoptosis of liver cancer cells. The study found that the expression level of hsa_circ_0000847 in liver cancer tissues and cells was significantly increased, while the expression level of miR-135a was significantly decreased. Hsa_circ_0000847 promoted the proliferation of liver cancer cells and elevated the expression of the proliferation-related protein. In addition, hsa_circ_0000847 could promote the invasion of HBV-infected liver cancer cells and inhibit the cell apoptosis of liver cancer cells. At the same time, it significantly promoted the expression of antiapoptotic proteins and inhibited the expression of proapoptotic protein. Interestingly, the dual luciferase experiment proved that hsa_circ_0000847 directly targeted miR-135a. On the other hand, the combined effect of hsa_circ_0000847 and miR-135a further illustrated the effect of hsa_circ_0000847 on the proliferation, invasion, and apoptosis of liver cancer cells. In addition, further experiments have also found that HBV could promote the expression of p-p38, p-ERK, and p-JNK through the hsa_circ_0000847/miR-135a axis, thereby further activating the MAPK pathway. In short, HBV promotes the proliferation and invasion of liver cancer cells and inhibits apoptosis by regulating the hsa_circ_0000847/miR-135a pathway, which provided a theoretical basis for effective treatment of HBV-infected liver cancers.

A Universal Method for Modeling and Characterizing Non-Circular Packing Systems Based on n-Point Correlation Functions.

A universal method for modeling and characterizing non-circular particles is developed. The n-point correlation functions (n = 1, 2 and 3) are efficiently computed with a GPU parallel computing procedure. An algorithm for dynamic packing of impenetrable non-circular particles is developed based on the fast estimation of overlap information using a one-point correlation function. The packing algorithm is independent of particle shape and proved to be reliable by examples of polygons and super-ellipses. In addition, penetrable packings are generated in an efficient and precise way. Using a two-point correlation function, these non-circular packs are accurately characterized and compared in terms of features such as penetrable and impenetrable, packing fraction and particle shape. In addition, three-point correlation functions are also illustrated and discussed.

Third-Order Effective Properties for Random-Packing Systems Using Statistical Micromechanics Based on a GPU Parallel Algorithm in Fast Computing n-Point Correlation Functions.

Estimating the effective properties of a particulate system is the most direct way to understand its macroscopic performance. In this work, we accurately evaluate the third-order approximations involving the three-point microstructural parameter ζ, which can be calculated from a triple integral involving 1-, 2-, and 3-point correlation functions. A GPU-based parallel algorithm was developed for quickly computing the n-point correlation functions, and the results agree well with analytical solutions. The effective thermal conductivity and diffusion coefficient are calculated by the third-order approximates for the random-packing systems of a super-ellipsoid. By changing the parameters of the super-ellipsoid, the particle-shape effect can be predicted for both the thermal conductivity and diffusion coefficient.