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1.
Mar Drugs ; 22(6)2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38921594

ABSTRACT

Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvß3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE's influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvß3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvß3. Activation of the integrin αvß3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.


Subject(s)
Blood Platelets , Human Umbilical Vein Endothelial Cells , Sepsis , von Willebrand Factor , Animals , Sepsis/drug therapy , von Willebrand Factor/metabolism , Humans , Mice , Human Umbilical Vein Endothelial Cells/drug effects , Male , Blood Platelets/drug effects , Blood Platelets/metabolism , Disease Models, Animal , Mice, Inbred C57BL , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Integrin alphaVbeta3/metabolism , Integrin alphaVbeta3/antagonists & inhibitors , Capillary Permeability/drug effects
2.
Anal Methods ; 16(25): 4150-4159, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38864437

ABSTRACT

Vegetable oil and animal fat residues are common evidence in the cases of homicide, arson, theft, and other crimes. However, the lipid composition and content changes during aging on complex carriers remain unclear. Therefore, this study dynamically monitored the lipid composition and content changes during aging of 13 different types of vegetable oils and animal fats on five different carriers using the UPLC-Q-Exactive Orbitrap MS method. A total of 6 subclasses of 93 lipids including lysophosphatidylcholine (2 species), phosphatidylcholine (2 species), diglyceride (5 species), triglyceride (81 species), acylGlcCampesterol ester (2 species), and acylGlcSitosterol ester (1 species), were first identified in fresh vegetable oils and animal fats. By comparing the LC-MS/MS chromatograms of fresh vegetable oils and animal fats, it was found that there were significant differences between the chromatograms of vegetable oils and animal fats, but it was difficult to distinguish between the chromatograms of vegetable oils or animal fats. After aging at 60 °C for 200 days, there was a significant decrease in the content of diglyceride, triglyceride, acylGlcCampesterol ester, and acylGlcSitosterol ester, while the content of lysophosphatidylcholine and phosphatidylcholine initially increased and then decreased. Furthermore, statistical analysis of lipid differences between vegetable oils and animal fats was performed using cluster heat maps, volcanic maps, PCA, and OPLS-DA. On average, 33 significantly different lipids were screened (VIP > 1, p < 0.05), which could serve as potential biomarkers for distinguishing vegetable oils and animal fats. It was found that the potential biomarkers still existed during aging of vegetable oils and animal fats (100 and 200 days). This research provides important reference information for the identification of vegetable oil and animal fat residues in complex carriers at crime scenes.


Subject(s)
Lipidomics , Plant Oils , Plant Oils/chemistry , Plant Oils/analysis , Animals , Chromatography, High Pressure Liquid/methods , Lipidomics/methods , Lipids/analysis , Tandem Mass Spectrometry/methods , Fats/chemistry , Fats/analysis
3.
Plant J ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38924231

ABSTRACT

Due to the chelation of phosphorus in the soil, it becomes unavailable for plant growth and development. The mechanisms by which phosphorus-solubilizing bacteria activate immobilized phosphorus to promote the growth and development of woody plants, as well as the intrinsic molecular mechanisms, are not clear. Through the analysis of microbial communities in the rhizosphere 16S V3-V4 and a homologous gene encoding microbial alkaline phosphomonoesterase (phoD) in phosphate-efficient (PE) and phosphate-inefficient apple rootstocks, it was found that PE significantly enriched beneficial rhizobacteria. The best phosphorus-solubilizing bacteria, Bacillus sp. strain 7DB1 (B2), was isolated, purified, and identified from the rhizosphere soil of PE rootstocks. Incubating with Bacillus B2 into the rhizosphere of apple rootstocks significantly increased the soluble phosphorus and flavonoid content in the rhizosphere soil. Simultaneously, this process stimulates the root development of the rootstocks and enhances plant phosphorus uptake. After root transcriptome sequencing, candidate transcription factor MhMYB15, responsive to Bacillus B2, was identified through heatmap and co-expression network analysis. Yeast one-hybrid, electrophoretic mobility shift assay, and LUC assay confirmed that MhMYB15 can directly bind to the promoter regions of downstream functional genes, including chalcone synthase MhCHS2 and phosphate transporter MhPHT1;15. Transgenic experiments with MhMYB15 revealed that RNAi-MhMYB15 silenced lines failed to induce an increase in flavonoid content and phosphorus levels in the roots under the treatment of Bacillus B2, and plant growth was slower than the control. In conclusion, MhMYB15 actively responds to Bacillus B2, regulating the accumulation of flavonoids and the uptake of phosphorus, thereby influencing plant growth and development.

4.
Heliyon ; 10(11): e31549, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38828349

ABSTRACT

Background: There is no standard consensus on the optimal number of cycles of neoadjuvant immunotherapy prior to surgery for patients with locoregionally advanced non-small cell lung cancer (NSCLC). We carried out a systematic review to evaluate the efficacy and safety of neoadjuvant immunotherapy with different treatment cycles in order to provide valuable information for clinical decision-making. Methods: PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were systematically searched before May 2023. The included studies were categorized based on different treatment cycles of neoadjuvant immunotherapy to assess their respective efficacy and safety in patients with resectable NSCLC. Results: Incorporating data from 29 studies with 1331 patients, we found major pathological response rates of 43 % (95%CI, 34-52 %) with two cycles and 33 % (95%CI, 22-45 %) with three cycles of neoadjuvant immunotherapy. Radiological response rates were 39 % (95%CI, 28-50 %) and 56 % (95%CI, 44-68 %) for two and three cycles, respectively, with higher incidence rates of severe adverse events (SAEs) in the three-cycle group (32 %; 95%CI, 21-50 %). Despite similar rates of R0 resection between two and three cycles, the latter showed a slightly higher surgical delay rate (1 % vs. 7 %). Neoadjuvant treatment modes significantly affected outcomes, with the combination of immunotherapy and chemotherapy demonstrating superiority in improving pathological and radiological response rates, while the incidence of SAEs in patients receiving combination therapy remained within an acceptable range (23 %; 95%CI, 15-35 %). However, regardless of the treatment mode administered, an increase in the number of treatment cycles did not result in substantial improvement in pathological response rates. Conclusion: There are clear advantages of combining immunotherapy and chemotherapy in neoadjuvant settings. Increasing the number of cycles of neoadjuvant immunotherapy from two to three primarily may not substantially improve the overall efficacy, while increasing the risk of adverse events. Further analysis of the outcomes of four cycles of neoadjuvant immunotherapy is necessary.

6.
Plant Dis ; 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38853332

ABSTRACT

Nanhaia speciosa, commonly known as Niudali, is a medicinal woody vine belonging to the Leguminosae family. Valued for its culinary and medicinal properties, it is extensively cultivated, covering approximately 5,973 hm2 in the Guangxi Zhuang Autonomous Region of China. The edible tubers of this plant are reported to possess antibacterial and antioxidant effects (Luo et al., 2023; Shu et al., 2020). In July 2021, a Niudali plantation in Yulin, Guangxi, China (22°64'N; 110°29'E) exhibited leaf spot symptoms, with an incidence rate exceeding 40% across a 46,690 m2 area. Initially, small circular, pale yellow spots appeared on the leaves, which subsequently evolved into dark brown lesions surrounded by yellow halos, ultimately leading to foliage wilting. Leaves exhibiting typical symptoms were collected for pathogen investigation. The leaves were thoroughly washed with sterile water and small tissue fragments (5×5 mm) were excised from the lesion periphery. These fragments were surface-sterilized with 75% ethanol and 1% NaClO, rinsed three times with sterile water, and subsequently cultured on potato dextrose agar (PDA) at 28 °C in darkness for 7 days. Through single-spore isolation, seven isolates with similar morphological traits were obtained. After 7 days of incubation on PDA at 28 °C in dark, the colonies exhibited a white to grey coloration on the upper surface with abundant aerial hyphae, while the underside appeared dark black. The conidia, cylindrical or obclavate in shape, were straight, pale brown, and measured 30.1-128.9 µm × 4.8-15.0 µm (n=50). The morphological characteristics matched those of Corynespora sp.(Wang et al. 2021). For molecular identification, the isolate N5-2 underwent DNA sequence analysis using genomic DNA and primers ITS1/ITS4 and EF1-688F/EF1-1251R. The sequences (ITS: OP550425; TEF1-α: OQ117118) were deposited in GenBank, exhibiting 98% identity to C. cassiicola (OP981637) for TEF1-α and 99% homology to C. cassiicola (OP957070) for ITS. Based on the concatenated ITS and TEF1-α, a maximum likelihood phylogenetic analyses using MEGA7.0 clustered the isolate with C. cassiicola. Consequently, the fungus was identified as C. cassiicola based on its morphological and molecular features. In the pathogenicity test on 1-year-old Nanhaia speciosa seedlings, leaves were gently scratched and inoculated with mycelial plugs (5 mm). Control seedlings received PDA plugs. Five leaves per plant and five plants per treatment were selected for assessment. All seedling were maintained in a greenhouse (12/12h light/dark cycle, 25 ± 2°C, 90% humidity). After a 7-day incubation period, all leaves subjected to fungal inoculation exhibited symptoms consistent with those observed in the field, while control plants remained symptom-free. The fungus was successfully reisolated from the infected leaves in three successive trials, fulfilling Koch's postulates. While C. cassiicola is well-documented for inducing leaf spots on various plant species, including Jasminum nudiflorum, Strobilanthes cusia, Acanthus ilicifolius, Syringa species (Hu et al., 2023; Liu et al., 2023; Xie et al., 2021; Wang et al., 2021), this study represents the first report of C. cassiicola causing leaf spots on Nanhaia speciosa in China. The identification of this pathogen in Nanhaia speciosa has significant implications for future epidemiological investigations and serves as a valuable reference for controlling leaf spot disease in Nanhaia speciosa.

7.
PNAS Nexus ; 3(6): pgae205, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38846777

ABSTRACT

Food safety is related to human health and sustainable development. International food trade poses food safety risks through the collateral transport of toxic chemicals that are detrimental to human health. Domestic interprovincial trade has similar effects within countries but has not been comprehensively investigated previously. Here, we assessed the effects of interprovincial trade on food safety and human dietary exposure to short-chain chlorinated paraffins (SCCPs), a group of emerging persistent toxic chemicals, in seafood across China by synthesizing data from field observation and various models. Our findings indicate that there is a higher level of SCCPs exposure risk in coastal provinces compared to inland provinces. Approximately, 70.3% of human exposure to SCCPs through seafood consumption in China was embodied in the interprovincial seafood trade in 2021. Specifically, the domestic trade led to a remarkable increase in SCCPs exposure in the coastal provinces in South China, attributable to low SCCPs pollution in these provinces and imported seafood from those provinces with high SCCPs pollution. In contrast, human exposure to SCCPs decreased in those coastal provinces in East China due to importing seafood from those provinces with low SCCPs concentrations. The interprovincial seafood trade routes were optimized by linear programming to minimize human exposure to SCCPs considering both shipping cost and health risk constraints. The optimized trade routes reduced the national per capita SCCPs exposure through seafood consumption by over 12%. This study highlights the importance of interprovincial food trade in the risk assessment of toxic chemicals.

8.
Int Endod J ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38828966

ABSTRACT

AIM: To evaluate the role of biomimetic pulp scaffolds derived from the extracellular matrix derived of stem cells from human exfoliated deciduous teeth (SHED-ECM-PS) in promoting pulp-dentine complex regeneration. METHODOLOGY: SHED-ECM-PS was prepared through cell aggregation and decellularization techniques. Histological and immunofluorescence analyses, scanning electron microscopy, and DNA quantification assays were used to characterize the SHED-ECM-PS. Additionally, a tooth slice implantation model was established to evaluate the effects of SHED-ECM-PS on regeneration of the pulp-dentine complex in vivo. Extraction medium for SHED-ECM-PS was prepared, and its effect on bone marrow mesenchymal stem cells (BMMSCs) was assessed in vitro. Cell counting kit-8 and Ki-67 staining assays were performed to determine cell proliferation. The rate of apoptosis was evaluated by flow cytometry. Wound healing and transwell assays were conducted to evaluate cell migration. Alizarin red S staining was performed to examine mineralized nodule formation. Western blotting was used to detect the expression of osteogenic and odontogenic markers. The results were analysed using an independent two-tailed Student's t-test. p < .05 was considered statistically significant. RESULTS: SHED-ECM-PS was successfully constructed, exhibiting a striped dental pulp-like shape devoid of nuclear structures or DNA components, and rich in fibronectin, collagen I, DMP1 and DSPP. Notably, SHED-ECM-PS showed no impact on the proliferation or apoptosis of BMMSCs. Histological analysis revealed that dental pulp fibroblasts formed an interwoven mesh in the root canal, and angiogenesis was observed in the SHED-ECM-PS group. Moreover, a continuous, newly formed tubular dentine layer with polarized odontoblast-like cells was observed along the inner wall of the root canal. SHED-ECM-PS promoted the migration, polar alignment and mineralized nodule formation of BMMSCs and specifically elevated the expression levels of odontogenic markers, but not osteogenic markers, compared with the control group in vitro. CONCLUSION: SHED-ECM-PS exhibited no cytotoxicity and promoted pulp-dentine complex regeneration in vivo as well as cell migration and odontogenic differentiation of BMMSCs in vitro. These findings provide evidence that SHED-ECM-PS, as a novel biological scaffold, has the potential to improve the outcomes of REPs.

9.
Clin J Oncol Nurs ; 28(3): 287-296, 2024 05 17.
Article in English | MEDLINE | ID: mdl-38830253

ABSTRACT

BACKGROUND: Providing effective health education is essential for patients with cancer-related pain. One solution is leveraging instant messaging tools for teach-back health education. OBJECTIVES: This study investigated the effects of WeChat-based teach-back health education on patients with advanced cancer who underwent patient-controlled intrathecal analgesia implantation and used hydromorphone. METHODS: This retrospective study evaluated 150 hospitalized patients with advanced cancer pain. Patients were classified into a conventional health education group (N = 50) and a teach-back group (N = 100) based on whether they received WeChat-based teach-back health education. Pain was rated using a numeric rating scale, and sleep quality was measured using the Pittsburgh Sleep Quality Index at one, two, and three months postdischarge. FINDINGS: Patients who received remote teach-back health education better managed their pain. Data also demonstrated improvements in patients' sleep quality and caregiver satisfaction, and reductions in the occurrence of adverse reactions.


Subject(s)
Cancer Pain , Patient Education as Topic , Humans , Male , Female , Middle Aged , Cancer Pain/drug therapy , Retrospective Studies , Aged , Patient Education as Topic/methods , Pain Management/methods , Adult , Neoplasms/complications , Pain Measurement
11.
BMC Oral Health ; 24(1): 658, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840089

ABSTRACT

BACKGROUND: Tooth avulsion represents the most severe form of dental trauma, necessitating tooth replantation as the primary treatment. However, the risk of replacement root resorption (RRR) poses a significant threat to tooth retention following replantation. This study preliminarily aimed to investigate the effect of physiological occlusal force on RRR after the replantation of avulsed teeth and to explore the potential underlying mechanisms. METHODS: Thirty-six 4-week-old male Sprague-Dawley rats underwent extraction and immediate replantation of their left maxillary molars. The rats were randomly divided into two major groups: the occluded (n = 18) group, where the opposite mandibular teeth were preserved; non-occluded (n = 18) group, where the opposite mandibular teeth were extracted. Within each major group, there were three subgroups corresponding to 7 days, 14 days, and 2 months, resulting in a total of six subgroups, (n = 6 per subgroup). The right maxillary first molars served as the normal control. Various periodontal characteristics were assessed using haematoxylin-eosin (H&E), tartrate-resistant acid phosphatase (TRAP) staining, and micro-computed tomography (micro-CT). RESULTS: Histological staining revealed that under occlusal force, the early stage (day 7) after tooth replantation mainly manifested as root surface resorption, especially in the non-occluded group, which gradually diminished over time. Cementum and periodontal ligament (PDL) repair was observed on day 14. Micro-CT analysis indicated a significant decrease in PDL width in the non-occluded group two months after replantation, consistent with the histological findings, signifying severe RRR in the non-occluded group. CONCLUSIONS: This study provides preliminary evidence that physiological occlusal force may attenuate osteoclastogenesis during the early stage of tooth replantation, thereby reducing the occurrence of RRR and promoting periodontal healing.


Subject(s)
Bite Force , Rats, Sprague-Dawley , Root Resorption , Tooth Avulsion , Tooth Replantation , X-Ray Microtomography , Animals , Root Resorption/etiology , Tooth Replantation/methods , Male , Tooth Avulsion/surgery , Rats , Molar/surgery
12.
J Cell Mol Med ; 28(11): e18484, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38842124

ABSTRACT

As an important protein encoded by hepatitis B virus (HBV), HBV X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). It has been shown that seven in absentia homologue 1 (SIAH1) could regulates the degradation of HBx through the ubiquitin-proteasome pathway. However, as a member of SIAH family, the regulatory effects of SIAH2 on HBx remain unclear. In this study, we first confirmed that SIAH2 could reduce the protein levels of HBx depending on its E3 ligase activity. Moreover, SIAH2 interacted with HBx and induced its K48-linked polyubiquitination and proteasomal degradation. Furthermore, we provided evidence that SIAH2 inhibits HBx-associated HCC cells proliferation by regulating HBx. In conclusion, our study identified a novel role for SIAH2 in promoting HBx degradation and SIAH2 exerts an inhibitory effect in the proliferation of HBx-associated HCC through inducing the degradation of HBx. Our study provides a new idea for the targeted degradation of HBx and may have great huge significance into providing novel evidence for the targeted therapy of HBV-infected HCC.


Subject(s)
Carcinoma, Hepatocellular , Cell Proliferation , Hepatitis B virus , Liver Neoplasms , Nuclear Proteins , Proteolysis , Trans-Activators , Ubiquitin-Protein Ligases , Ubiquitination , Viral Regulatory and Accessory Proteins , Humans , Viral Regulatory and Accessory Proteins/metabolism , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/virology , Trans-Activators/metabolism , Trans-Activators/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/virology , Liver Neoplasms/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Hepatitis B virus/metabolism , Hepatitis B virus/pathogenicity , Cell Line, Tumor , Signal Transduction , Hep G2 Cells
13.
J Colloid Interface Sci ; 673: 239-248, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38871627

ABSTRACT

Applications of zinc-air batteries are partially limited by the slow kinetics of oxygen reduction reaction (ORR); Thus, developing effective strategies to address the compatibility issue between performance and stability is crucial, yet it remains a significant challenge. Here, we propose an in situ gas etching-thermal assembly strategy with an in situ-grown graphene-like shell that will favor Mn anchoring. Gas etching allows for the simultaneous creation of mesopore-dominated carbon cores and ultrathin carbon layer shells adorned entirely with highly dispersed Mn-N4 single-atom sites. This approach effectively resolves the compatibility issue between activity and stability in a single step. The unique core-shell structure allows for the full exposure of active sites and effectively prevents the agglomerations and dissolution of Mn-N4 sites in cores. The corresponding half-wave potential for ORR is up to 0.875 V (vs. reversible hydrogen electrode (RHE)) in 0.1 M KOH. The gained catalyst (Mn-N@Gra-L)-assembled zinc-air battery has a high peak power density (242 mW cm-2) and a durability of âˆ¼ 115 h. Furthermore, replacing the zinc anode achieved a stable cyclic discharge platform of âˆ¼ 20 h at varying current densities. Forming more fully exposed and stable existing Mn-N4 sites is a governing factor for improving the electrocatalytic ORR activity, significantly cycling durability, and reversibility of zinc-air batteries.

14.
Materials (Basel) ; 17(11)2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38894034

ABSTRACT

Although quartz powder is a common concrete filling material, the importance and originality of this study lies in the development of a hydration model for quartz powder-cement binary mixtures and the adoption of this model to predict the development of concrete material properties. The purpose of this study is to use this model to promote the material design of environmentally friendly concrete and to elucidate the relationships in the development of the various properties of quartz powder concrete. The method used in this study was as follows: The parameters of the hydration model were obtained through seven days of hydration heat experiments. The hydration heat up to 28 days was also calculated, and the various properties of the concrete were predicted from the heat of hydration. The main findings of this study were as follows: (1) The ultimate hydration heat released per gram of cement for the different quartz powder substitution rates and quartz powder particle fineness was the same, at 390.145 J/g cement, as was the shape index of the hydration model at -1.003. (2) Moreover, through the model calculations, we found that, at the twenty-eighth day of the curing period for the quartz powder specimens with different quartz powder substitution amounts and different fineness, the reaction level of the cement was similar, at 0.963, as were the values of the cumulative heat of hydration, with both at 375.5 J/g cement. (3) The model showed that, in the late stage (28 days) of hydration for quartz powders of different fineness and when the substitution amount was the same, the cumulative heat of hydration over 28 days was similar. (4) The properties of concrete were evaluated using the calculated hydration heat. Overall, the predictive performance of the power and linear functions was similar, with no significant differences being found.

15.
BMC Microbiol ; 24(1): 206, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858614

ABSTRACT

OBJECTIVE: This study aims to examine the impact of PE/PPE gene mutations on the transmission of Mycobacterium tuberculosis (M. tuberculosis) in China. METHODS: We collected the whole genome sequencing (WGS) data of 3202 M. tuberculosis isolates in China from 2007 to 2018 and investigated the clustering of strains from different lineages. To evaluate the potential role of PE/PPE gene mutations in the dissemination of the pathogen, we employed homoplastic analysis to detect homoplastic single nucleotide polymorphisms (SNPs) within these gene regions. Subsequently, logistic regression analysis was conducted to analyze the statistical association. RESULTS: Based on nationwide M. tuberculosis WGS data, it has been observed that the majority of the M. tuberculosis burden in China is caused by lineage 2 strains, followed by lineage 4. Lineage 2 exhibited a higher number of transmission clusters, totaling 446 clusters, of which 77 were cross-regional clusters. Conversely, there were only 52 transmission clusters in lineage 4, of which 9 were cross-regional clusters. In the analysis of lineage 2 isolates, regression results showed that 4 specific gene mutations, PE4 (position 190,394; c.46G > A), PE_PGRS10 (839,194; c.744 A > G), PE16 (1,607,005; c.620T > G) and PE_PGRS44 (2,921,883; c.333 C > A), were significantly associated with the transmission of M. tuberculosis. Mutations of PE_PGRS10 (839,334; c.884 A > G), PE_PGRS11 (847,613; c.1455G > C), PE_PGRS47 (3,054,724; c.811 A > G) and PPE66 (4,189,930; c.303G > C) exhibited significant associations with the cross-regional clusters. A total of 13 mutation positions showed a positive correlation with clustering size, indicating a positive association. For lineage 4 strains, no mutations were found to enhance transmission, but 2 mutation sites were identified as risk factors for cross-regional clusters. These included PE_PGRS4 (338,100; c.974 A > G) and PPE13 (976,897; c.1307 A > C). CONCLUSION: Our results indicate that some PE/PPE gene mutations can increase the risk of M. tuberculosis transmission, which might provide a basis for controlling the spread of tuberculosis.


Subject(s)
Mutation , Mycobacterium tuberculosis , Polymorphism, Single Nucleotide , Tuberculosis , Whole Genome Sequencing , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/classification , Mycobacterium tuberculosis/isolation & purification , China/epidemiology , Humans , Tuberculosis/transmission , Tuberculosis/microbiology , Tuberculosis/epidemiology , Genome, Bacterial , Female , Male , Bacterial Proteins/genetics , Adult
16.
Nat Commun ; 15(1): 5209, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890388

ABSTRACT

Despite the importance of spliceosome core components in cellular processes, their roles in cancer development, including hepatocellular carcinoma (HCC), remain poorly understood. In this study, we uncover a critical role for SmD2, a core component of the spliceosome machinery, in modulating DNA damage in HCC through its impact on BRCA1/FANC cassette exons and expression. Our findings reveal that SmD2 depletion sensitizes HCC cells to PARP inhibitors, expanding the potential therapeutic targets. We also demonstrate that SmD2 acetylation by p300 leads to its degradation, while HDAC2-mediated deacetylation stabilizes SmD2. Importantly, we show that the combination of Romidepsin and Olaparib exhibits significant therapeutic potential in multiple HCC models, highlighting the promise of targeting SmD2 acetylation and HDAC2 inhibition alongside PARP inhibitors for HCC treatment.


Subject(s)
Carcinoma, Hepatocellular , Exons , Liver Neoplasms , Phthalazines , Piperazines , Poly(ADP-ribose) Polymerase Inhibitors , Spliceosomes , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Acetylation , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Spliceosomes/metabolism , Spliceosomes/drug effects , Cell Line, Tumor , Phthalazines/pharmacology , Exons/genetics , Piperazines/pharmacology , Animals , BRCA1 Protein/metabolism , BRCA1 Protein/genetics , Depsipeptides/pharmacology , Depsipeptides/therapeutic use , Mice , DNA Damage/drug effects , Gene Expression Regulation, Neoplastic/drug effects
17.
Cell Commun Signal ; 22(1): 337, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38898461

ABSTRACT

Killer cell lectin-like receptor G1 (KLRG1) is an immune checkpoint receptor expressed predominantly in NK and T-cell subsets that downregulates the activation and proliferation of immune cells and participates in cell-mediated immune responses. Accumulating evidence has demonstrated the importance of KLRG1 as a noteworthy disease marker and therapeutic target that can influence disease onset, progression, and prognosis. Blocking KLRG1 has been shown to effectively mitigate the effects of downregulation in various mouse tumor models, including solid tumors and hematologic malignancies. However, KLRG1 inhibitors have not yet been approved for human use, and the understanding of KLRG1 expression and its mechanism of action in various diseases remains incomplete. In this review, we explore alterations in the distribution, structure, and signaling pathways of KLRG1 in immune cells and summarize its expression patterns and roles in the development and progression of autoimmune diseases, infectious diseases, and cancers. Additionally, we discuss the potential applications of KLRG1 as a tool for tumor immunotherapy.


Subject(s)
Lectins, C-Type , Neoplasms , Receptors, Immunologic , Humans , Receptors, Immunologic/metabolism , Lectins, C-Type/metabolism , Lectins, C-Type/antagonists & inhibitors , Animals , Neoplasms/metabolism , Neoplasms/drug therapy , Neoplasms/immunology , Biomarkers/metabolism , Signal Transduction , Autoimmune Diseases/metabolism , Autoimmune Diseases/immunology , Autoimmune Diseases/drug therapy , Immunotherapy
18.
Ultrason Sonochem ; 108: 106957, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38901304

ABSTRACT

In industrial production and scientific research, ultrasonic cavitation technology, with its outstanding physical and chemical processing capabilities, has been widely applied in fields such as material surface modification, chemical synthesis, and biotechnology, becoming a focal point of research and application. This article delves into the effects of different ultrasonic frequencies on cavitation outcomes through the combined use of numerical simulation, fluorescence analysis, and high-speed photography, specifically analyzing the quantitative improvement in the mechanical properties of TC17 titanium alloy under ultrasonic cavitation at frequencies of 20 kHz, 30 kHz, and 40 kHz. The study found that at an ultrasonic frequency of 20 kHz, the maximum expansion radius of cavitation bubbles can reach 51.4 µm, 8.6 times their initial radius. Correspondingly, fluorescence intensity and peak area also increased to 402.8 and 28104, significantly above the baseline level. Moreover, after modification by ultrasonic cavitation, the original machining marks on the surface of TC17 titanium alloy became fainter, with the emergence of new, uniformly distributed microfeatures. The microhardness of the material increased from 373.7 Hv to 383.84 Hv, 396.62 Hv, and 414.06 Hv, with a maximum improvement of 10.8 %. At the same time, surface height difference and roughness significantly decreased (to 3.168 µm and 0.61 µm respectively), with reductions reaching 45.1 % and 42.4 %, indicating a significant improvement in material surface quality. Notably, there is a negative correlation between the improvement of mechanical properties and ultrasonic frequency, suggesting that the improvement effects decrease as ultrasonic frequency increases. This research not only reveals the quantitative relationship between ultrasonic cavitation frequency and material surface modification effects but also provides a solid scientific basis and practical guidance for the application of ultrasonic cavitation technology in surface engineering, signifying the technology's potential for broad application in the future.

19.
Food Chem ; 457: 140098, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38901345

ABSTRACT

To understand the influence of ß-glucans structure on the emulsifying properties of protein-polysaccharide conjugates, sodium caseinate (NaCas) was utilized to form glycosylation conjugates with varying degrees of glycosylation (10.68-17.50%) using three ß-glucans from bacteria, yeast, and oats. This process induced alterations in the secondary structure of protein. The nanoemulsions prepared with the glycosylated conjugates exhibited superior stability compared to those formulated solely with NaCas, particularly under conditions of drastic pH fluctuations and extended storage periods. The nanoemulsion prepared with the NaCas-Salecan conjugate demonstrated exceptional stability at pH 4 and 6, or storage for 20 days. Additionally, it significantly attenuated the oxidation of unsaturated fatty acids and exhibited the lowest levels of aggregation, flocculation, and free fatty acid release rate during in vitro digestion. This study suggested the potential of the NaCas-Salecan conjugates in enhancing the stability of nanoemulsions and facilitating the colorectal-targeted delivery of sea buckthorn fruit oil.

20.
BMC Pulm Med ; 24(1): 280, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877486

ABSTRACT

BACKGROUND: The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare. CASE PRESENTATION: A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant 18F-FDG uptake on 18F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis. CONCLUSION: Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.


Subject(s)
Bone Neoplasms , Lymphocytosis , Pleural Neoplasms , Thymoma , Humans , Female , Middle Aged , Thymoma/pathology , Thymoma/diagnostic imaging , Thymoma/complications , Thymoma/diagnosis , Lymphocytosis/pathology , Lymphocytosis/diagnosis , Pleural Neoplasms/secondary , Pleural Neoplasms/pathology , Pleural Neoplasms/complications , Pleural Neoplasms/diagnosis , Bone Neoplasms/secondary , Positron Emission Tomography Computed Tomography , Thymus Neoplasms/pathology , Thymus Neoplasms/complications , Thymus Neoplasms/diagnosis , T-Lymphocytes/pathology , Fluorodeoxyglucose F18 , Diagnosis, Differential , Pleura/pathology , Pleura/diagnostic imaging
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