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1.
J Environ Sci (China) ; 148: 591-601, 2025 Feb.
Article in English | MEDLINE | ID: mdl-39095192

ABSTRACT

To explore air contamination resulting from special biomass combustion and suspended dust in Lhasa, the present study focused on the size distribution and chemical characteristics of particulate matter (PM) emission resulting from 7 types of non-fossil pollution sources. We investigated the concentration and size distribution of trace elements from 7 pollution sources collected in Lhasa. Combining Lhasa's atmospheric particulate matter data, enrichment factors (EFs) have been calculated to examine the potential impact of those pollution sources on the atmosphere quality of Lhasa. The highest mass concentration of total elements of biomass combustion appeared at PM0.4, and the second highest concentration existed in the size fraction 0.4-1 µm; the higher proportion (12 %) of toxic metals was produced by biomass combustion. The elemental composition of suspended dust and atmospheric particulate matter was close (except for As and Cd); the highest concentration of elements was all noted in PM2.5-10 (PM3-10). Potassium was found to be one of the main biomass markers. The proportion of Cu in suspended dust is significantly lower than that of atmospheric particulate matter (0.53 % and 3.75 %), which indicates that there are other anthropogenic sources. The EFs analysis showed that the Cr, Cu, Zn, and Pb produced by biomass combustion were highly enriched (EFs > 100) in all particle sizes. The EFs of most trace elements increased with decreasing particle size, indicating the greater influence of humanfactors on smaller particles.


Subject(s)
Aerosols , Air Pollutants , Dust , Environmental Monitoring , Particle Size , Particulate Matter , Air Pollutants/analysis , Aerosols/analysis , Particulate Matter/analysis , Dust/analysis , Trace Elements/analysis , Air Pollution/statistics & numerical data , Air Pollution/analysis , China , Atmosphere/chemistry
2.
Am J Gastroenterol ; 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39382852

ABSTRACT

INTRODUCTION: The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study. METHODS: In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected eight-week) or to four-week postpartum (expected twelve-week) were randomly enrolled at a 1:1 ratio and followed until six-month postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary endpoint was the safety of mothers and infants. The secondary endpoint was infants' HBV-MTCT rate at seven months of age. RESULTS: Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in two groups completed the study. Overall, TAF was well tolerated, no one discontinued therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n=231) and at seven months (n=222) were normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at seven months of age. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) versus 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the two groups had mildly elevated alanine aminotransferase levels at three-month and six-month postpartum, respectively (P=0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] versus 0% [0/120, 0%-3.1%]). DISCUSSION: Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected eight-week prenatal duration is feasible. ClinicalTrials.gov, NCT04850950.

3.
J Nanobiotechnology ; 22(1): 598, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39363196

ABSTRACT

BACKGROUND: Surgeries for treating pelvic organ prolapse involving the utilization of synthetic mesh have been associated with complications such as mesh erosion, postoperative pain, and dyspareunia. This work aimed to reduce the surgical implantation-associated complications by nanofibrous membranes on the surface of the polypropylene mesh. The nanofiber of the nanofibrous membrane, which was fabricated by co-axial electrospinning, was composed of polyurethane as fiber core and gelatin as the fiber out layer. The biocompatibility of the modified mesh was evaluated in vitro by cell proliferation assay, immunofluorescence stain, hematoxylin-eosin (HE) staining, and mRNA sequencing. Polypropylene mesh and modified mesh were implanted in a rat pelvic organ prolapse model. Mesh-associated complications were documented. HE and Picro-Sirius red staining, immunohistochemistry, and western blotting were conducted to assess the interactions between the modified mesh and vaginal tissues. RESULTS: The modified mesh significantly enhanced the proliferation of fibroblasts and exerted a positive regulatory effect on the extracellular matrix anabolism in vitro. When evaluated in vivo, no instances of mesh exposure were observed in the modified mesh group. The modified mesh maintained a relatively stable histological position without penetrating the muscle layer or breaching the epidermis. The collagen content in the vaginal wall of rats with modified mesh was significantly higher, and the collagen I/III ratio was lower, indicating better tissue elasticity. The expression of metalloproteinase was decreased while the expression levels of tissue inhibitor of metalloproteinase were increased in the modified mesh group, suggesting an inhibition of collagen catabolism. The expression of TGF-ß1 and the phosphorylation levels of Smad3, p38 and ERK1/2 were significantly increased in the modified mesh group. NM significantly improved the biocompatibility of PP mesh, as evidenced by a reduction in macrophage count, decreased expression levels of TNF-α, and an increase in microvascular density. CONCLUSIONS: The nanofibrous membrane-coated PP mesh effectively reduced the surgical implantation complications by inhibiting the catabolism of collagen in tissues and improving the biocampibility of PP mesh. The incorporation of co-axial fibers composed of polyurethane and gelatin with polypropylene mesh holds promise for the development of enhanced surgical materials for pelvic organ prolapse in clinical applications.


Subject(s)
Cell Proliferation , Nanofibers , Pelvic Organ Prolapse , Polypropylenes , Rats, Sprague-Dawley , Surgical Mesh , Animals , Nanofibers/chemistry , Female , Rats , Polypropylenes/chemistry , Pelvic Organ Prolapse/surgery , Vagina/surgery , Vagina/metabolism , Fibroblasts/metabolism , Postoperative Complications , Polyurethanes/chemistry , Biocompatible Materials/chemistry , Membranes, Artificial
4.
JCI Insight ; 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39361424

ABSTRACT

Accumulation of extracellular matrix (ECM) proteins in trabecular meshwork (TM), which leads to increased outflow resistance of aqueous humor and consequently high intraocular pressure, is a major cause of primary open-angle glaucoma (POAG). According to our preliminary research, the RapGAP protein superfamily member, signal-induced proliferation-associated 1-like 1 protein (SIPA1L1), which is involved in tissue fibrosis, may have an impact on POAG by influencing ECM metabolism of TM. This study aims to confirm these findings and identify effects and cellular mechanisms of SIPA1L1 on ECM changes and phagocytosis in human TM (HTM) cells. Our results showed that the expression of SIPA1L1 in HTM cells was significantly increased by TGFß2 treatment in Label-free quantitative proteomics. The aqueous humor and TM cells concentration of SIPA1L1 in POAG patients was higher than that of control. In HTM cells, TGFß2 increased expression of SIPA1L1 along with accumulation of ECM, RhoA and p-Cofilin1. The effects of TGFß2 were reduced by si-SIPA1L1. TGFß2 decreased HTM cell phagocytosis by polymerizing cytoskeletal actin filaments, while si-SIPA1L1 increased phagocytosis by disassembling actin filaments. Simultaneously, overexpressing SIPA1L1 alone exhibited comparable effects to that of TGFß2. Our studies demonstrate that SIPA1L1 not only promotes the production of ECM, but also inhibits its removal by reducing phagocytosis. Targeting SIPA1L1 degradation may become a significant therapy for POAG.

5.
PLoS One ; 19(9): e0309646, 2024.
Article in English | MEDLINE | ID: mdl-39264942

ABSTRACT

OBJECTIVE: This study aimed to evaluate the safety and efficacy of skull-femoral traction followed by osteotomy correction in patients with severe spinal scoliosis and split cord malformation. METHODS: We retrospectively analyzed ten cases of severe spinal scoliosis with Pang I type split cord malformation treated between August 2012 and August 2023. Patients underwent skull-femoral traction prior to osteotomy correction. We assessed changes in height, weight, coronal and sagittal Cobb's angles, and physiological indicators such as vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and blood gas levels before, during, and after treatment. RESULTS: Traction duration ranged from 9 to 19 days, with height and weight showing significant increases post-treatment. The coronal Cobb's angle improved from pre-treatment to post-corrective surgery and remained stable at the final follow-up. Similar improvements were observed in the sagittal plane. Physiological indicators such as VC, FVC, and FEV1, as well as blood gas levels, normalized after treatment. Nutritional status, indicated by triceps skinfold thickness, albumin, and transferrin concentrations, also improved. No neurological complications or device-related complications occurred during or after treatment. CONCLUSION: Skull-femoral traction followed by osteotomy correction is a safe and effective treatment for severe spinal scoliosis with split cord malformation, offering an alternative to high-risk procedures.


Subject(s)
Osteotomy , Scoliosis , Skull , Traction , Humans , Female , Scoliosis/surgery , Osteotomy/methods , Male , Traction/methods , Child , Adolescent , Retrospective Studies , Skull/surgery , Skull/abnormalities , Treatment Outcome , Femur/surgery , Femur/abnormalities
6.
Mol Med Rep ; 30(5)2024 11.
Article in English | MEDLINE | ID: mdl-39301637

ABSTRACT

Lung cancer has the highest incidence and mortality rates of all cancer types in China and therefore represents a serious threat to human health. In the present study, the mechanism of rabdoternin E against the proliferation of the lung cancer cell line A549 was explored. It was found that rabdoternin E caused the accumulation of large amounts of reactive oxygen species (ROS), promoted cell S phase arrest by reducing the expression of CDK2 and cyclin A2, induced apoptosis by increasing the Bax/Bcl­2 ratio and promoted the phosphorylation of proteins in the ROS/p38 MAPK/JNK signaling pathway, which is associated with apoptosis and ferroptosis. In addition, it was also found that Z­VAD­FMK (an apoptosis inhibitor), ferrostatin­1 (ferroptosis inhibitor) and N­acetylcysteine (a ROS inhibitor) could partially or greatly reverse the cytotoxicity of rabdoternin E to A549 cells. Similarly, NAC (N­acetylcysteine) treatment notably inhibited the rabdoternin E­stimulated p38 MAPK and JNK activation. Furthermore, in vivo experiments in mice revealed that Rabdoternin E markedly reduced tumor volume and weight and regulated the expression levels of apoptosis and ferroptosis­related proteins (including Ki67, Bcl­2, Bax, glutathione peroxidase 4, solute carrier family 7 member 11 and transferrin) in the tumor tissues of mice. Histopathological observation confirmed that the number of tumor cells decreased markedly after administration of rabdoternin E. Taken together, rabdoternin E induced apoptosis and ferroptosis of A549 cells by activating the ROS/p38 MAPK/JNK signaling pathway. Therefore, the results of the present study showed that rabdoternin E is not toxic to MCF­7 cells (normal lung cells), had no significant effect on body weight and was effective and therefore may be a novel therapeutic treatment for lung cancer.


Subject(s)
Apoptosis , Lung Neoplasms , MAP Kinase Signaling System , Reactive Oxygen Species , p38 Mitogen-Activated Protein Kinases , Humans , Reactive Oxygen Species/metabolism , Animals , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , p38 Mitogen-Activated Protein Kinases/metabolism , MAP Kinase Signaling System/drug effects , Mice , A549 Cells , Apoptosis/drug effects , Xenograft Model Antitumor Assays , Cell Proliferation/drug effects , Cell Line, Tumor , Ferroptosis/drug effects , Mice, Nude , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use
7.
Brain Imaging Behav ; 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39331345

ABSTRACT

To explore the cortical microstructural alterations in Parkinson's disease (PD) at different stages. 149 PD patients and 76 healthy controls were included. PD patients were divided into early stage PD (EPD) (Hoehn-Yahr stage ≤ 2) and moderate-to-late stage PD (MLPD) (Hoehn-Yahr stage ≥ 2.5) according to their Hoehn-Yahr stages. All participants underwent two-shell diffusion MRI and the images were fitted to Neurite Orientation Dispersion and Density Imaging (NODDI) model to obtain the neurite density index (NDI) and orientation dispersion index (ODI) to reflect the cortical microstructure. We used gray matter-based spatial statistics method to compare the voxel-wise cortical NODDI metrics between groups. Partial correlation was used to correlate the NODDI metrics and global composite outcome in PD patients. Compared with healthy controls, EPD patients showed lower ODI in widespread regions, covering bilateral frontal, temporal, parietal and occipital cortices, as well as regional lower NDI in bilateral cingulate and frontal lobes. Compared with healthy controls, MLPD patients showed lower ODI and NDI in more widespread regions. Compared with EPD patients, MLPD patients showed lower ODI in bilateral temporal, parietal and occipital cortices, where the ODI values were negatively correlated with global composite outcome in PD patients. PD patients showed widespread cortical microstructural degeneration, characterized by reduced neurite density and orientation dispersion, and the cortical neuritic microstructure exhibit progressive degeneration during the progression of PD.

8.
Environ Pollut ; 362: 124961, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39299634

ABSTRACT

It was indispensable to seek effective and feasible measures to alleviate the adverse effects of wastewater irrigation. Nanoscale zerovalent iron (nZVI) and soil nitrogen management might enhance the vegetable yield and quality but mitigate the potential human-disease risks from wastewater irrigation. This study selected the nZVI and nitrification inhibitor as experimental objects. The planted pakchoi cabbage was irrigated with the tap water and wastewater and treated with nZVI and 3, 4-dimethylpyrazole phosphate (DMPP), respectively, the pakchoi cabbage yield and quality, soil enzyme activity and abiotic property, and human-disease risk of bacterial community were quantified. Compared with the control, the nZVI significantly enhanced the pakchoi cabbage yield by 51.5% but reduced the pakchoi cabbage nitrate content by 52.6% under wastewater irrigation condition. The nZVI alone had double-edged sword effects of increasing the pakchoi cabbage yield, reducing the pakchoi cabbage nitrate content and soil human-disease risk but inhibiting the system multifunctionality and soil bacterial community diversity and stability, under wastewater irrigation condition. The nZVI diminished human-disease risk via increasing the soil Firmicutes and Verrucomicrobiota ratios, and the extra DMPP could mitigate the negative effects of nZVI by increasing soil enzyme activity and stimulating soil Acidobacteria ratio. The combinations of nZVI and DMPP could not only enhance the pakchoi cabbage yield and quality but also reduce the human-disease risk of soil bacterial community from wastewater irrigation.

9.
Front Endocrinol (Lausanne) ; 15: 1425101, 2024.
Article in English | MEDLINE | ID: mdl-39229373

ABSTRACT

Purpose: To develop a predictive model using machine learning for levothyroxine (L-T4) dose selection in patients with differentiated thyroid cancer (DTC) after resection and radioactive iodine (RAI) therapy and to prospectively validate the accuracy of the model in two institutions. Methods: A total of 266 DTC patients who received RAI therapy after thyroidectomy and achieved target thyroid stimulating hormone (TSH) level were included in this retrospective study. Sixteen clinical and biochemical characteristics that could potentially influence the L-T4 dose were collected; Significant features correlated with L-T4 dose were selected using machine learning random forest method, and a total of eight regression models were established to assess their performance in prediction of L-T4 dose after RAI therapy; The optimal model was validated through a two-center prospective study (n=263). Results: Six significant clinical and biochemical features were selected, including body surface area (BSA), weight, hemoglobin (HB), height, body mass index (BMI), and age. Cross-validation showed that the support vector regression (SVR) model was with the highest accuracy (53.4%) for prediction of L-T4 dose among the established eight models. In the two-center prospective validation study, a total of 263 patients were included. The TSH targeting rate based on constructed SVR model were dramatically higher than that based on empirical administration (Rate 1 (first rate): 52.09% (137/263) vs 10.53% (28/266); Rate 2 (cumulative rate): 85.55% (225/263) vs 53.38% (142/266)). Furthermore, the model significantly shortens the time (days) to achieve target TSH level (62.61 ± 58.78 vs 115.50 ± 71.40). Conclusions: The constructed SVR model can effectively predict the L-T4 dose for postoperative DTC after RAI therapy, thus shortening the time to achieve TSH target level and improving the quality of life for DTC patients.


Subject(s)
Iodine Radioisotopes , Thyroid Neoplasms , Thyroidectomy , Thyroxine , Humans , Thyroxine/blood , Thyroxine/administration & dosage , Thyroxine/therapeutic use , Male , Female , Middle Aged , Thyroid Neoplasms/surgery , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/therapy , Iodine Radioisotopes/therapeutic use , Iodine Radioisotopes/administration & dosage , Adult , Retrospective Studies , Prospective Studies , Machine Learning , Thyrotropin/blood , Aged , Postoperative Period
10.
Plants (Basel) ; 13(18)2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39339568

ABSTRACT

Submergence stress challenges direct seeding in rice cultivation. In this study, we identified a heat shock protein, NAL11, with a DnaJ domain, which can regulate the length of rice coleoptiles under flooded conditions. Through bioinformatics analyses, we identified cis-regulatory elements in its promoter, making it responsive to abiotic stresses, such as hypoxia or anoxia. Expression of NAL11 was higher in the basal regions of shoots and coleoptiles during flooding. NAL11 knockout triggered the rapid accumulation of abscisic acid (ABA) and reduction of Gibberellin (GA), stimulating rice coleoptile elongation and contributes to flooding stress management. In addition, NAL11 mutants were found to be more sensitive to ABA treatments. Such knockout lines exhibited enhanced cell elongation for coleoptile extension. Quantitative RT-PCR analysis revealed that NAL11 mediated the gluconeogenic pathway, essential for the energy needed in cell expansion. Furthermore, NAL11 mutants reduced the accumulation of reactive oxygen species (ROS) and malondialdehyde under submerged stress, attributed to an improved antioxidant enzyme system compared to the wild-type. In conclusion, our findings underscore the pivotal role of NAL11 knockout in enhancing the tolerance of rice to submergence stress by elucidating its mechanisms. This insight offers a new strategy for improving resilience against flooding in rice cultivation.

11.
J Food Sci ; 89(10): 6378-6393, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39245923

ABSTRACT

ABSTRAC: Female adult Eupolyphaga sinensis Walker (FAESW) has traditionally been a food source in Southeast Asian countries such as China and India, due to its rich nutritional content. However, the nutritional value of male adults (MAESW) and its molts (MESW) has hardly been reported. Therefore, this study aims to explore the potential application of MAESW and MESW in food by investigating and comparing their nutritional composition (i.e., protein, amino acids, fatty acids, and essential elements) with traditional sources of nutrition. The protein content of MAESW and MESW was 66.10 ± 0.49% and 59.86 ± 6.07%, respectively, and the highest energy content (462.26 ± 1.28 kcal/100 g) was observed for MAESW. Eight essential amino acids were determined, of which the males and MESW were found to have higher contents than those of FAESW (p < 0.05). Oleic and linoleic acid contents were higher in the adults than nymphs. Moreover, MESW was predominant in calcium (6770.84 mg/kg), whereas MAESW was rich in iron (556.12 mg/kg). Likened to chicken, the protein, amino acid, fatty acid, and mineral contents of ESW were higher. The volatiles of ESW were related to hexaldehyde, benzaldehyde, acetic acid, and butyric acid. This study provides a better understanding of the chemical composition of ESWs during their growth cycle and helps optimize information on edible insects, promoting their use as a potential food source for humans. PRACTICAL APPLICATION: As a kind of edible insect, the utilization of adult male Eupolyphaga sinensis Walker (ESW) and its molt is very low at present. Therefore, this study examined the nutrients and volatile substances of ESW (at different growth stages) and molt, which provided a theoretical basis for the subsequent development and utilization of ESW.


Subject(s)
Amino Acids , Fatty Acids , Nutritive Value , Nymph , Volatile Organic Compounds , Animals , Male , Female , Volatile Organic Compounds/analysis , Fatty Acids/analysis , Amino Acids/analysis , Nymph/growth & development , China
13.
Front Vet Sci ; 11: 1455338, 2024.
Article in English | MEDLINE | ID: mdl-39280835

ABSTRACT

Understanding the differences in ubiquitination-modified proteins between Duroc pigs and Tibetan fragrant pigs is crucial for comprehending the growth and development of their skeletal muscles. In this study, skeletal muscle samples from 30-day-old Duroc pigs and Tibetan fragrant pigs were collected. Using ubiquitination 4D-Label free quantitative proteomics, we analyzed and identified ubiquitination-modified peptides, screening out 109 differentially expressed ubiquitination-modified peptides. Further enrichment analysis was conducted on the proteins associated with these differential peptides. GO analysis results indicated that the differential genes were primarily enriched in processes such as regulation of protein transport, motor activity, myosin complex, and actin cytoskeleton. KEGG pathway analysis revealed significant enrichment in pathways such as Glycolysis/Gluconeogenesis and Hippo signaling pathway. The differentially expressed key ubiquitinated proteins, including MYL1, MYH3, TNNC2, TNNI1, MYLPF, MYH1, MYH7, TNNT2, TTN, and TNNC1, were further identified. Our analysis demonstrates that these genes play significant roles in skeletal muscle protein synthesis and degradation, providing new insights into the molecular mechanisms of muscle development in Duroc pigs and Tibetan fragrant pigs, and offering theoretical support for breeding improvements in the swine industry.

14.
J Colloid Interface Sci ; 678(Pt A): 827-841, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39217698

ABSTRACT

Herein, an interpenetrating network hydrogel (IPN-Gel) based on cellulose and chitosan was synthesized via simultaneous amino-anhydride and azide-alkyne click reaction in water in one pot. The samples were characterized by various analytical methods including FTIR, SEM, XRD, XPS, 1H NMR and so forth. The fabrication conditions were optimized by single factor experiments with water uptake (WU) and gel mass fraction (GMF) as two indexes. The WU and GMF of the IPN-Gel prepared under optimized conditions were 1192.37 % and 74.00 %, respectively. Its WU descended with the ascension in temperature, and first descended and then gradually ascended with the ascension in pH, confirming that the IPN-Gel had thermal/pH dual responsiveness. Using 5-Fu as a model drug, the release behavior of 5-Fu in IPN-Gel was explored. Its release behavior could be regulated by changing temperature and pH values, and it followed the Korsmeyer Peppas model. The viability of 4 T1 cells and HUVEC cells exceeded 80 % after 48 h of incubation at a high concentration of 200 µg/mL IPN-Gel, and hemolytic percentage was below the allowed limit of 5 %. The study provides a new strategy for the preparation of the IPN-Gel with biocompatibility, swelling reversibility and controllable drug release.

15.
J Cell Physiol ; : e31426, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39221900

ABSTRACT

Dysregulation of alternative pre-mRNA splicing plays a critical role in the progression of cancers, yet the underlying molecular mechanisms remain largely unknown. It is reported that metastasis-associated in colon cancer 1 (MACC1) is a novel prognostic and predictive marker in many types of cancers, including lung adenocarcinoma. Here, we reveal that the oncogene MACC1 specifically drives the progression of lung adenocarcinoma through its control over cancer-related splicing events. MACC1 depletion inhibits lung adenocarcinoma progression through triggering IRAK1 from its long isoform, IRAK1-L, to the shorter isoform, IRAK1-S. Mechanistically, MACC1 interacts with splicing factor HNRNPH1 to prevent the production of the short isoform of IRAK1 mRNA. Specifically, the interaction between MACC1 and HNRNPH1 relies on the involvement of MACC1's SH3 domain and HNRNPH1's GYR domain. Further, HNRNPH1 can interact with the pre-mRNA segment (comprising exon 11) of IRAK1, thereby bridging MACC1's regulation of IRAK1 splicing. Our research not only sheds light on the abnormal splicing regulation in cancer but also uncovers a hitherto unknown function of MACC1 in tumor progression, thereby presenting a novel potential therapeutic target for clinical treatment.

16.
J Med Chem ; 67(17): 15711-15737, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39169676

ABSTRACT

The NLRP3 inflammasome is a multiprotein complex that is a component of the innate immune system, involved in the production of pro-inflammatory cytokines. Its abnormal activation is associated with many inflammatory diseases. In this study, we designed and synthesized a series of NLRP3 inflammasome inhibitors based on pyridazine scaffolds. Among them, P33 exhibited significant inhibitory effects against nigericin-induced IL-1ß release in THP-1 cells, BMDMs, and PBMCs, with IC50 values of 2.7, 15.3, and 2.9 nM, respectively. Mechanism studies indicated that P33 directly binds to NLRP3 protein (KD = 17.5 nM), inhibiting NLRP3 inflammasome activation and pyroptosis by suppressing ASC oligomerization during NLRP3 assembly. Additionally, P33 displayed excellent pharmacokinetic properties, with an oral bioavailability of 62%. In vivo efficacy studies revealed that P33 significantly ameliorated LPS-induced septic shock and MSU crystal-induced peritonitis in mice. These results indicate that P33 has great potential for further development as a candidate for treating NLRP3 inflammasome-mediated diseases.


Subject(s)
Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Peritonitis , Pyridazines , Shock, Septic , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Peritonitis/drug therapy , Animals , Shock, Septic/drug therapy , Humans , Inflammasomes/antagonists & inhibitors , Inflammasomes/metabolism , Mice , Pyridazines/chemistry , Pyridazines/pharmacology , Pyridazines/pharmacokinetics , Pyridazines/chemical synthesis , Pyridazines/therapeutic use , Administration, Oral , Male , Mice, Inbred C57BL , THP-1 Cells , Structure-Activity Relationship , Drug Discovery , Interleukin-1beta/metabolism , Interleukin-1beta/antagonists & inhibitors , Lipopolysaccharides/pharmacology
17.
Bioresour Technol ; 413: 131376, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39214173

ABSTRACT

The aerobic granular sludge (AGS) process had been extensively studied for its simultaneous nitrification and denitrification (SND) capabilities. Iron-carbon (IC) had enhanced AGS nitrogen removal efficiency, but the mechanism remained unclear. In this study, four reactors had been added with 50, 30, 10, and 0 g/L of IC. Total nitrogen removal efficiency increased with IC dosage under the same operation mode. IC enhanced sludge ammonia oxidation rate, denitrification rate, and specific oxygen uptake rate, allowing SND to complete 60 min earlier, potentially reducing wastewater treatment costs. Notably, IC eliminated nitrite accumulation in conventional AGS effluent. IC decreased the abundance of genes and enzyme activities related to NOR expression, while increasing those related to NOS, which may mitigate the potential for nitrous oxide formation by microorganisms. In this study, IC acted as an enzymatic reaction activator, affecting granules more than flocs, with the activity gap gradually decreasing with the IC dosage.

18.
PLoS One ; 19(8): e0307392, 2024.
Article in English | MEDLINE | ID: mdl-39167617

ABSTRACT

This study examined the relationships among vocational students' perceptions of school service quality, their learning satisfaction, and their conceptions of vocational education in Chinese secondary vocational schools. Using a quantitative approach, data were collected from 10,721 students through multistage sampling. Perceived school service quality was assessed using the five-factor SERVPERF instrument, learning satisfaction was measured with the one-factor SSwLA scale, and conceptions of vocational education were evaluated using the one-factor SCoVE scale. These instruments were subjected to internal, convergent, discriminant, and construct validity tests, including exploratory and confirmatory factor analyses. Structural equation modeling (SEM) analyzed the relationships among the constructs. Additionally, mediation analysis was employed to explore the mediating role of students' conceptions of vocational education in the relationship between perceived school service quality and learning satisfaction. Results indicated that learning satisfaction was positively influenced by students' perceptions of school service quality, particularly responsiveness, assurance, reliability, and empathy, but negatively by tangibles. Furthermore, the association between students' perceived school service quality and learning satisfaction was mediated by their conceptions of vocational education, highlighting the complex interaction between perceived service quality and students' learning satisfaction. These findings provide critical insights for policymakers and educators seeking to enhance effectiveness and satisfaction within vocational education settings.


Subject(s)
Learning , Personal Satisfaction , Schools , Students , Vocational Education , Humans , Male , Female , Students/psychology , Adolescent , Surveys and Questionnaires , Perception , China
19.
World J Gastrointest Oncol ; 16(8): 3559-3584, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39171190

ABSTRACT

BACKGROUND: Gastric cancer (GC) is a common malignant tumor, long non-coding RNA and microRNA (miRNA) are important regulators that affect tumor proliferation, metastasis and chemotherapy resistance, and thus participate in tumor progression. CASC19 is a new bio-marker which can promote tumor invasion and metastasis. However, the mechanism by which CASC19 affects the progression of GC through miRNA is not clear. AIM: To explore the role of the CASC19/miR-491-5p/HMGA2 regulatory axis in GC. METHODS: To explore the expression and prognosis of CASC19 in GC through clinical samples, and investigate the effects of inhibiting CASC19 on the proliferation, migration, invasion and other functions of GC cells through cell counting Kit-8 (CCK-8), ethynyldeoxyuridine, Wound healing assay, Transwell, Western blot and flow cytometry experiments. The effect of miR-491-5p and HMGA2 in GC were also proved. The regulatory relationship between CASC19 and miR-491-5p, miR-491-5p and HMGA2 were validated through Dual-luciferase reporter gene assay and reverse transcription PCR. Then CCK-8, Transwell, Wound healing assay, flow cytometry and animal experiments verify the role of CASC19/miR-491-5p/HMGA2 regulatory axis. RESULTS: The expression level of CASC19 is related to the T stage, N stage, and tumor size of patients. Knockdown of the expression of CASC19 can inhibit the ability of proliferation, migration, invasion and EMT conversion of GC cells, and knocking down the expression of CASC19 can promote the apoptosis of GC cells. Increasing the expression of miR-491-5p can inhibit the proliferation of GC cells, miR-491-5p mimics can inhibit EMT conversion, and promote the apoptosis of GC cells, while decreasing the expression of miR-491-5p can promote the proliferation and EMT conversion and inhibit the apoptosis of GC cells. The expression of HMGA2 in GC tissues is higher than that in adjacent tissues. At the same time, the expression level of HMGA2 is related to the N and T stages of the patients. Reducing the level of HMGA2 can promote cell apoptosis and inhibit the proliferation of GC cells. Cell experiments and animal experiments have proved that CASC19 can regulates the expression of HMGA2 through miR-491-5p, thereby affecting the biological functions of GC. CONCLUSION: CASC19 regulates the expression of HMGA2 through miR-491-5p to affect the development of GC. This axis may serve as a potential biomarker and therapeutic target of GC.

20.
Environ Res ; 262(Pt 1): 119792, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39142455

ABSTRACT

The functionality of activated sludge in wastewater treatment processes depends largely on the structural and microbial composition of its flocs, which are complex assemblages of microorganisms and their secretions. However, monitoring these flocs in real-time and consistently has been challenging due to the lack of suitable technologies and analytical methods. Here we present a laboratory setup capable of capturing instantaneous microscopic images of activated sludge, along with algorithms to interpret these images. To improve floc identification, an advanced Mask R-CNN-based segmentation that integrates a Dual Attention Network (DANet) with an enhanced Feature Pyramid Network (FPN) was used to enhance feature extraction and segmentation accuracy. Additionally, our novel PointRend module meticulously refines the contours of boundaries, significantly minimising pixel inaccuracies. Impressively, our approach achieved a floc detection accuracy of >95%. This development marks a significant advancement in real-time sludge monitoring, offering essential insights for optimising wastewater treatment operations proactively.

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