Proteomic and phosphoproteomic profiling of urinary small extracellular vesicles in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and a major cause of cancer-related mortality worldwide. Small extracellular vesicles (sEVs) are heterogeneous populations of membrane-structured vesicles that can be found in many biological fluids and are currently considered as a potential source of disease-associated biomarkers for diagnosis. The purpose of this study was to define the proteomic and phosphoproteomic landscape of urinary sEVs in patients with HCC. Mass spectrometry-based methods were used to detect the global proteome and phosphoproteome profiles of sEVs isolated by differential ultracentrifugation. Label-free quantitation analysis showed that 348 differentially expressed proteins (DEPs) and 548 differentially expressed phosphoproteins (DEPPs) were identified in the HCC group. Among them, multiple phosphoproteins related to HCC, including HSP90AA1, IQGAP1, MTOR, and PRKCA, were shown to be upregulated in the HCC group. Pathway enrichment analysis indicated that the upregulated DEPPs participate in the regulation of autophagy, proteoglycans in cancer, and the MAPK/mTOR/Rap1 signaling pathway. Furthermore, kinase-substrate enrichment analysis revealed activation of MTOR, AKT1, MAP2Ks, and MAPKs family kinases in HCC-derived sEVs, indicating that dysregulation of the MAPK and mTOR signaling pathways may be the primary sEV-mediated molecular mechanisms involved in the development and progression of HCC. This study demonstrated that urinary sEVs are enriched in proteomic and phosphoproteomic signatures that could be further explored for their potential use in early HCC diagnostic and therapeutic applications.

Exosomal encapsulation of miR-3198 promotes proliferation and migration of trophoblasts in preeclampsia.

PURPOSE: Preeclampsia (PE) is a vascular remodeling disorder cloesly linked to trophoblast dysfunction, involving defects in their proliferation, migration, and apoptosis. Maternal exosomal microRNAs (miRNAs) have been reported to play pivotal roles in the development of PE. However, the mechanism underlying the role of maternal exosomes in trophoblast dysfunction regarding the development of PE is poorly understood. METHODS: Plasma exosomes from maternal peripheral blood were collected from pregnant women with PE and from those with normal pregnancy. Bioinformatics analysis was used to identify significantly differentially expressed miRNAs under these two conditions. The expression of the miR-3198 gene in plasma exosomes was detected using quantitative real-time polymerase chain reaction. Dual luciferase reporter assay was used to confirm binding of miR-3198 and 3'UTR region of WNT3. Cell proliferation was examined using the Cell Count Kit-8 and EdU assays, and flow cytometry was performed to detect apoptosis and cell cycle. Changes in cell migration were examined using transwell and scratch assays. RESULTS: Patients with PE showed decreased expression of plasma-derived exosomal miR-3198. The proliferation and migration abilities of HTR-8/SVneo and primary human trophoblast cells were both improved when cocultured with miR-3198-rich exosomes. Exposure to miR-3198-enriched exosomes facilitated cell cycle progression but reduced apoptosis in HTR-8/SVneo cells. Notably, overexpression of miR-3198 partially prevented the inhibitory effects of WNT3 on proliferation and migration in HTR-8/SVneo cells. CONCLUSION: Exosomal miR-3198 in the maternal peripheral blood may regulate the biological functions of trophoblasts by targeting WNT3 and influence the development of diseases of placental origin.

Afforestation enhances glomalin-related soil protein content but decreases its contribution to soil organic carbon in a subtropical karst area.

Afforestation on degraded croplands has been proposed as an effective measure to promote ecosystem functions including soil organic carbon (SOC) sequestration. Glomalin-related soil protein (GRSP) plays a crucial role in promoting the accumulation and stability of SOC. Nevertheless, mechanisms underlying the effects of afforestation on GRSP accumulation have not been well elucidated. In the present study, 14 pairs of maize fields and plantation forests were selected using a paired-site approach in a karst region of southwest China. By measuring soil GRSP and a variety of soil biotic and abiotic variables, the pattern of and controls on GRSP accumulation in response to afforestation were explored. The average content of total GRSP (T-GRSP) and its contribution to SOC in the maize field were 5.22 ± 0.29 mg g-1 and 42.33 ± 2.25%, and those in the plantation forest were 6.59 ± 0.32 mg g-1 and 25.77 ± 1.17%, respectively. T-GRSP content was increased by 26.4% on average, but its contribution to SOC was decreased by 39.1% following afforestation. T-GRSP content decreased as soil depth increased regardless of afforestation or not. Afforestation increased T-GRSP indirectly via its positive effects on arbuscular mycorrhizal fungi biomass, which was stimulated by afforestation through elevating fine root biomass or increasing the availability of labile C and N. The suppressed contribution of T-GRSP to SOC following afforestation was due to the relatively higher increase in other SOC components than T-GRSP and the significant increase of soil C:N ratio. Our study reveals the mechanisms underlying the effects of afforestation on T-GRSP accumulation, and is conducive to improving the mechanistic understanding of microbial control on SOC sequestration following afforestation.

Mechanism underlying effects of cellulose-degrading microbial inoculation on amino acid degradation and biosynthesis during composting.

Amino acids are essential organic compounds in composting products. However, the mechanism underlying the amino acid metabolism during composting remains unclear. This study aims at exploring the impacts of inoculating cellulose-degrading microbes on amino acid metabolism during composting with mulberry branches and silkworm excrements. Cellulose-degrading microbial inoculation enhanced amino acid degradation by 18%-43% by increasing protease and sucrase activities and stimulating eight amino acid degradation pathways from the initial to thermophilic phases, with Enterococcus, Saccharomonospora, Corynebacterium being the dominant bacterial genera, but stimulated amino acid production by 54% by increasing sucrase and urease activities, decreasing ß-glucosidase activities, and stimulating twenty-two amino acid synthesis pathways at the mature phase, with Thermobifida, Devosia, and Cellulosimicrobium being the dominant bacterial genera. The results suggest that cellulose-degrading microbial inoculation enhances amino acid degradation from the initial to thermophilic phases and biosynthesis at the mature phase, thereby improving the quality of organic fertilizer.

Protective Effects of Polysaccharide of Atractylodes Macrocephala Koidz against Porcine Aortic Valve Endothelial Cells Damage Induced by di (2-ethylhexyl) Phthalate.

The activation, injury, and dysfunction of endothelial cells are considered to be the initial key events in the development of atherosclerosis. Di (2-ethylhexyl) phthalate (DEHP), a prevalent organic pollutant, can cause damage to multiple organs. Polysaccharide of Atractylodes macrocephala Koidz (PAMK) is a bioactive compound extracted from A. macrocephala Koidz with various biological activities. This study investigates the protective effects of PAMK on porcine aortic valve endothelial cells (PAVEC) damaged by DEHP. PAVECs treated with DEHP alone or with PAMK showed reduced cell apoptosis and death in PAMK-pretreated cells. PAMK up-regulated Bcl-2 expression and down-regulated Bax protein, suppressing apoptosis. Flow cytometry analysis demonstrated that PAMK protected PAVECs from DEHP-induced damage. These findings suggest that PAMK inhibits cell apoptosis and protects against DEHP damage in endothelial cells.

Identification of novel compound heterozygous variants of the ALMS1 gene in a child with Alström syndrome by whole genome sequencing.

BACKGROUND: Alström syndrome (ALMS), a rare recessively inherited ciliopathy caused by mutations in ALMS1, is characterized by retinal dystrophy, childhood obesity, sensorineural hearing loss, and type 2 diabetes mellitus. The majority of pathogenic variants in ALMS1 are nonsense and frameshift mutations, which would lead to premature protein truncation, whereas copy number variants are seldom reported. METHODS: Herein, we present a 10-year-old Chinese girl with ALMS. The potential causative genetic variant was confirmed through whole genome sequencing, quantitative real-time PCR analysis, and Sanger sequencing. Additionally, breakpoint analysis was performed to determine the exact breakpoint site of the large deletion and elucidate its probable formation mechanism. RESULTS: The patient had a cor triatriatum sinister (CTS) structure. Genetic analysis identified novel compound heterozygous variants in the patient, consisting of a frameshift variant c.4414_4415delGT (p.V1472Nfs*26) in ALMS1 and a novel large deletion at chr2:73,612,355-73,626,339, which encompasses exon 1 of the ALMS1 gene. Moreover, breakpoint analysis revealed that the large deletion probably formed through the microhomology-mediated end joining (MMEJ) mechanism due to the 6-bp microhomologies (TCCTTC) observed at both ends of the breakpoints. CONCLUSIONS: In this study, novel compound heterozygous variants in the ALMS1 gene were identified in an ALMS patient with a CTS structure. The molecular confirmation of these variants expands the mutational spectrum of ALMS1, while the manifestation of ALMS in the patient provides additional clinical insights into this syndrome.

A study on the DAM-EfficientNet hail rapid identification algorithm based on FY-4A_AGRI.

Hail, a highly destructive weather phenomenon, necessitates critical identification and forecasting for the protection of human lives and properties. The identification and forecasting of hail are vital for ensuring human safety and safeguarding assets. This research proposes a deep learning algorithm named Dual Attention Module EfficientNet (DAM-EfficientNet), based on EfficientNet, for detecting hail weather conditions. DAM-EfficientNet was evaluated using FY-4A satellite imagery and real hail fall records, achieving an accuracy of 98.53% in hail detection, a 97.92% probability of detection, a false alarm rate of 2.08%, and a critical success index of 95.92%. DAM-EfficientNet outperforms existing deep learning models in terms of accuracy and detection capability, with fewer parameters and computational needs. The results validate DAM-EfficientNet's effectiveness and superior performance in hail weather detection. Case studies indicate that the model can accurately forecast potential hail-affected areas and times. Overall, the DAM-EfficientNet model proves to be effective in identifying hail weather, offering robust support for weather disaster alerts and prevention. It holds promise for further enhancements and broader application across more data sources and meteorological parameters, thereby increasing the precision and timeliness of hail forecasting to combat hail disasters and boost public safety.

Construction of High-Performance Anode of Potassium-Ion Batteries by Stripping Covalent Triazine Frameworks with Molten Salt.

Covalent triazine frameworks (CTFs) are promising battery electrodes owing to their designable functional groups, tunable pore sizes, and exceptional stability. However, their practical use is limited because of the difficulty in establishing stable ion adsorption/desorption sites. In this study, a melt-salt-stripping process utilizing molten trichloro iron (FeCl3) is used to delaminate the layer-stacked structure of fluorinated covalent triazine framework (FCTF) and generate iron-based ion storage active sites. This process increases the interlayer spacing and uniformly deposits iron-containing materials, enhancing electron and ion transport. The resultant melt-FeCl3-stripped FCTF (Fe@FCTF) shows excellent performance as a potassium ion battery with a high capacity of 447 mAh g-1 at 0.1 A g-1 and 257 mAh g-1 at 1.6 A g-1 and good cycling stability. Notably, molten-salt stripping is also effective in improving the CTF's Na+ and Li+ storage properties. A stepwise reaction mechanism of K/Na/Li chelation with C═N functional groups is proposed and verified by in situ X-ray diffraction testing (XRD), ex-situ X-ray photoelectron spectroscopy (XPS), and theoretical calculations, illustrating that pyrazines and iron coordination groups play the main roles in reacting with K+/Na+/Li+ cations. These results conclude that the Fe@FCTF is a suitable anode material for potassium-ion batteries (PIBs), sodium-ion batteries (SIBs), and lithium-ion batteries (LIBs).

[Abundance of denitrifying genes and their driving factors in soil under different land use types in the karst region of Northwest Guangxi]. / æ¡‚è¥¿åŒ—å²©æº¶åŒºä¸åŒåœŸåœ°åˆ©ç”¨æ–¹å¼ä¸‹åœŸå£¤åç¡åŒ–åŸºå› ä¸°åº¦åŠå ¶é©±åŠ¨å› ç´ .

To understand the role of denitrifying microbes during vegetation recovery in karst regions, we determined the basic physicochemical properties and abundance of denitrifying microbial functional genes (nirS, nirK, fungal nirK, p450nor, and nosZ) of 13 collected soil samples under three land use types (cropland, grassland, and plantation) in Northwest Guangxi, and investigated the changes in the abundance of denitrifying microbial functional genes and their driving factors. Results showed that soil pH, soil organic carbon, total nitrogen (TN), and exchangeable calcium (Caexe) in plantation soil were significantly higher than those in cropland and grassland. The abundance of nirS, nirK, p450nor, and nosZ in plantation soil were significantly higher than those in cropland and grassland. Soil pH, TN, and Caexe were positively correlated with the abundance of denitrifying functional genes nirS, nirK, and p450nor. Results of redundancy analysis showed that soil Caexe, pH and TN were the primary factors influencing the abundance of denitrifying functional genes, which accounted for 34.1%, 20.1%, and 16.1% of the total variation, respectively. Such a result suggested that Caexe was the main driver of changes in denitrifying functional genes under different land use types. Overall, vegetation restoration (plantation) could effectively increase soil denitrifying microbe genes abundance in the karst region of Northwest Guangxi, and consequently influence soil nitrogen cycling.