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1.
Sci Data ; 11(1): 576, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834644

ABSTRACT

Exopalaemon carinicauda, a eurythermal and euryhaline shrimp, contributes one third of the total biomass production of polyculture ponds in eastern China and is considered as a potential ideal experimental animal for research on crustaceans. We conducted a high-quality chromosome-level genome assembly of E. carinicauda combining PacBio HiFi and Hi-C sequencing data. The total assembly size was 5.86 Gb, with a contig N50 of 235.52 kb and a scaffold N50 of 138.24 Mb. Approximately 95.29% of the assembled sequences were anchored onto 45 pseudochromosomes. BUSCO analysis revealed that 92.89% of 1,013 single-copy genes were highly conserved orthologs. A total of 44, 288 protein-coding genes were predicted, of which 70.53% were functionally annotated. Given its high heterozygosity (2.62%) and large proportion of repeat sequences (71.49%), it is one of the most complex genome assemblies. This chromosome-scale genome will be a valuable resource for future molecular breeding and functional genomics research on E. carinicauda.


Subject(s)
Chromosomes , Genome , Palaemonidae , Animals , Palaemonidae/genetics , China , Molecular Sequence Annotation
2.
Front Pediatr ; 12: 1334139, 2024.
Article in English | MEDLINE | ID: mdl-38836246

ABSTRACT

Background and objectives: Childhood obesity is highly prevalent worldwide. We aimed to assess whether serum 25-hydroxyvitamin D was associated with general/central obesity among US adolescents, and further to explore the mediatory impact of homeostasis model assessment of insulin resistance (HOMA-IR) on this association. Methods: This study is cross-sectional in design. Study adolescents were enrolled from the National Health and Nutrition Examination Survey (NHANES), 2011-2018. Serum 25-hydroxyvitamin D categories associated with general (indexed by body mass index) and central (indexed by waist circumference to height ratio) obesity were regressed. The possible mediatory effect of HOMA-IR on this association was explored. The nonlinear and dose-response association was examined by restricted cubic spline (RCS) test. Results: Total 2,696 adolescents were eligible for inclusion, and the mean age of all adolescents was 15.4 years. Overall, the percentage of general and central obesity was 38.0% and 38.6%, respectively. Compared with adolescents with sufficient vitamin D, adolescent with deficient and insufficient vitamin D intake were associated with general obesity and central obesity; fully-adjusted OR for general obesity was 1.602 (95% CI: 1.161-2.211) and 1.659 (1.385-1.986), and fully-adjusted OR for central obesity was 2.025 (1.445-2.837) and 1.557 (1.287-1.884), respectively, while there was no observable significance in adolescents with possibly harmful vitamin D. The proportion mediated by HOMA-IR was estimated to be 31.7% for global obesity and 50.3% for central obesity (both P < 0.05). More stratified analyses were presented, and identified that the association with general obesity was particularly present among Mexican American, while with central obesity among Non-Hispanic Black adolescents. Conclusions: Our findings indicate that deficient or insufficient 25-hydroxyvitamin D concentrations were associated with the significant risk of general and central obesity among US adolescents, and approximately 30% and 50%, respectively, of these associations were mediated by HOMA-IR.

3.
Front Microbiol ; 15: 1389046, 2024.
Article in English | MEDLINE | ID: mdl-38832118

ABSTRACT

Introduction: Microplastics (MPs), identified as emerging contaminants, have been detected across diverse environmental media. Their enduring presence and small size facilitate the adsorption of organic pollutants and heavy metals, leading to combined pollution effects. MPs also accumulate in the food chain thus pose risks to animals, plants, and human health, garnering significant scholarly attention in recent years. Aerobic granular sludge (AGS) technology emerges as an innovative approach to wastewater treatment. However, the impacts of MPs on the operational efficiency and microbial characteristics of AGS systems has been insufficiently explored. Methods: This study investigated the effects of varying concentration (10, 50, and 100 mg/L) of biodegradable MPs (Polylactic Acid, PLA) and non-biodegradable MPs (Polyethylene Terephthalate, PET) on the properties of AGS and explored the underlying mechanisms. Results and discussions: It was discovered that low and medium concentration of MPs (10 and 50 mg/L) showed no significant effects on COD removal by AGS, but high concentration (100 mg/L) of MPs markedly diminished the ability to remove COD of AGS, by blocking most of the nutrient transport channels of AGS. However, both PLA and PE promoted the nitrogen and phosphorus removal ability of AGS, and significantly increased the removal efficiency of total inorganic nitrogen (TIN) and total phosphorus (TP) at stages II and III (P < 0.05). High concentration of MPs inhibited the growth of sludge. PET noticeably deteriorate the sedimentation performance of AGS, while 50 mg/L PLA proved to be beneficial to sludge sedimentation at stage II. The addition of MPs promoted the abundance of Candidatus_Competibacter and Acinetobacter in AGS, thereby promoting the phosphorus removal capacity of AGS. Both 50 mg/L PET and 100 mg/L PLA caused large amount of white Thiothrix filamentous bacteria forming on the surface of AGS, leading to deterioration of the sludge settling performance and affecting the normal operation of the reactor. Comparing with PET, AGS proved to be more resistant to PLA, so more attention should be paid to the effect of non-biodegradable MPs on AGS in the future.

4.
Molecules ; 29(9)2024 May 02.
Article in English | MEDLINE | ID: mdl-38731598

ABSTRACT

Obtaining high-added value compounds from agricultural waste receives increasing attention, as it can both improve resource utilization efficiency and reduce waste generation. In this study, polysaccharides are extracted from the discarded roots of Abelmoschus manihot (L.) by the high-efficiency ultrasound-assisted extraction (UAE). The optimized condition was determined as solid-liquid ratio SL ratio = 1:20, temperature T = 30 °C and time T = 40 min, achieving an extraction yield of 13.41%. Composition analysis revealed that glucose (Glc, 44.65%), rhamnose (Rha, 26.30%), galacturonic acid (GalA, 12.50%) and galactose (Gal, 9.86%) are the major monosaccharides of the extract. The extract showed a low degree of esterification (DE) value of 40.95%, and its Fourier-transform infrared (FT-IR) spectrum exhibited several characteristic peaks of polysaccharides. Inspired by the wide cosmetic applications of polysaccharides, the skincare effect of the extract was evaluated via the moisture retention, total phenolic content (TPC) quantification, 2,2-Diphenyl-1-picrylhydrazyl (DPPH)-free radical scavenging activity, anti-hyaluronidase and anti-elastase activity experiments. The extract solutions demonstrated a 48 h moisture retention rate of 10.75%, which is superior to that of commercially available moisturizer hyaluronic acid (HA). Moreover, both the TPC value of 16.16 mg GAE/g (dw) and DPPH-free radical scavenging activity of 89.20% at the concentration of 2 mg/mL indicated the strong anti-oxidant properties of the extract. Furthermore, the anti-hyaluronidase activity and moderate anti-elastase activity were determined as 72.16% and 42.02%, respectively. In general, in vitro skincare effect experiments suggest moisturizing, anti-oxidant, anti-radical and anti-aging activities of the A. manihot root extract, indicating its potential applications in the cosmetic industry.


Subject(s)
Abelmoschus , Antioxidants , Plant Extracts , Plant Roots , Polysaccharides , Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/isolation & purification , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistry , Abelmoschus/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Spectroscopy, Fourier Transform Infrared , Skin Care/methods , Rhamnose/chemistry , Galactose , Hexuronic Acids/chemistry , Phenols/chemistry , Phenols/analysis , Phenols/pharmacology , Humans
5.
Scand J Gastroenterol ; : 1-10, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38741565

ABSTRACT

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a first-line therapy to treat GERD. Recently, the potassium-competitive acid inhibitors have been increasingly in use in clinical practice. We aimed to evaluate the efficacy and safety of P-CABs in GERD. METHODS: We searched PubMed, the Cochrane Library, EMBASE and Web Of Science for publications regarding randomized controlled trials comparing potassium-competitive acid inhibitors to PPI monotherapy or Placebo with respect to efficacy and safety in GERD (until April 2023). The primary outcome was an absence or global symptom improvement and the incidence of adverse events in GERD. The quality of the included literature was assessed using the bias assessment tool recommended in the Cochrane Systematic Assessor's Handbook 5.1.0. We use RevMan 5.3 software for Meta-analysis, sensitivity analysis and publication bias analysis. RESULTS: Of the 991 screened studies, 14 studies including 4868 participants were analyzed. The ORs for the healing rates of GERD with P-CABs versus PPI/Placebo were 2.10 (95% confidence interval [CI] 1.53-2.88), additionally, 1.09 (95% CI 1.05-1.14), 1.03 (95% CI 1.00-1.06) and 1.03 (95% CI 0.99-1.06) in Weeks 2, 4, and 8, respectively. The effectiveness rate of the experimental group was significantly higher than that of the control group (RR 1.73; 95% CI 1.27-2.36). The overall OR of Incidence of adverse events with P-CABs versus PPI/Placebo was 1.08 (95% CI 0.88-1.12). Overall, the risk of bias was low to some concerns. Furthermore, sensitivity analyses confirmed the robustness of the study's conclusion. CONCLUSIONS: Our findings suggest that potassium-competitive acid inhibitors is non-inferior to PPIs as therapy for patients with GERD. The safety outcomes for potassium-competitive acid inhibitors are similar to those for PPIs.

6.
Nat Med ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750350

ABSTRACT

Heat exposure is associated with an increased risk of preterm birth (PTB), with previous work suggesting that maternal blood pressure may play a role in these associations. Here we conducted a cohort study of 197,080 singleton live births across 8 provinces in China from 2015 to 2018. The study first estimated the associations between heat exposure, maternal hypertension and clinical subtypes of PTB, and then quantified the role of maternal hypertension in heat and PTB using mediation analyses. We show that heat exposure (>85th, 90th and 95th percentiles of local temperature distributions) spanning from conception to the 20th gestational week was associated with a 15-21% increase in PTB, and a 20-22% increase in medically indicated PTB. Heat exposure is likely to increase the risk of maternal hypertension and elevated blood pressure. Maternal hypertension mediated 15.7% and 33.9% of the effects of heat exposure (>90th percentile) on PTB and medically indicated PTB, respectively. Based on this large-population study, we found that exposure to heat in early pregnancy can increase the risk of maternal hypertension, thereby affecting the incidence of PTB.

7.
Nat Commun ; 15(1): 4124, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750026

ABSTRACT

Basal progenitor cells are crucial for maintaining foregut (the esophagus and forestomach) homeostasis. When their function is dysregulated, it can promote inflammation and tumorigenesis. However, the mechanisms underlying these processes remain largely unclear. Here, we employ genetic mouse models to reveal that Jag1/2 regulate esophageal homeostasis and foregut tumorigenesis by modulating the function of basal progenitor cells. Deletion of Jag1/2 in mice disrupts esophageal and forestomach epithelial homeostasis. Mechanistically, Jag1/2 deficiency impairs activation of Notch signaling, leading to reduced squamous epithelial differentiation and expansion of basal progenitor cells. Moreover, Jag1/2 deficiency exacerbates the deoxycholic acid (DCA)-induced squamous epithelial injury and accelerates the initiation of squamous cell carcinoma (SCC) in the forestomach. Importantly, expression levels of JAG1/2 are lower in the early stages of human esophageal squamous cell carcinoma (ESCC) carcinogenesis. Collectively, our study demonstrates that Jag1/2 are important for maintaining esophageal and forestomach homeostasis and the onset of foregut SCC.


Subject(s)
Carcinogenesis , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Esophagus , Homeostasis , Jagged-1 Protein , Jagged-2 Protein , Stem Cells , Animals , Jagged-1 Protein/metabolism , Jagged-1 Protein/genetics , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Esophageal Neoplasms/metabolism , Esophagus/pathology , Esophagus/metabolism , Stem Cells/metabolism , Mice , Jagged-2 Protein/metabolism , Jagged-2 Protein/genetics , Humans , Carcinogenesis/genetics , Carcinogenesis/pathology , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/metabolism , Mice, Knockout , Signal Transduction , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Receptors, Notch/metabolism , Receptors, Notch/genetics , Cell Differentiation , Male , Female
8.
Int J Oncol ; 64(6)2024 Jun.
Article in English | MEDLINE | ID: mdl-38757341

ABSTRACT

Ferroptosis, a recently discovered type of programmed cell death triggered by excessive accumulation of iron­dependent lipid peroxidation, is linked to several malignancies, including non­small cell lung cancer. Long non­coding RNAs (lncRNAs) are involved in ferroptosis; however, data on their role and mechanism in cancer therapy remains limited. Therefore, the aim of the present study was to identify ferroptosis­associated mRNAs and lncRNAs in A549 lung cancer cells treated with RAS­selective lethal 3 (RSL3) and ferrostatin­1 (Fer­1) using RNA sequencing. The results demonstrated that lncRNA lung cancer­associated transcript 1 (LUCAT1) was significantly upregulated in lung adenocarcinoma and lung squamous cell carcinoma tissues. Co­expression analysis of differentially expressed mRNAs and lncRNAs suggested that LUCAT1 has a crucial role in ferroptosis. LUCAT1 expression was markedly elevated in A549 cells treated with RSL3, which was prevented by co­incubation with Fer­1. Functionally, overexpression of LUCAT1 facilitated cell proliferation and reduced the occurrence of ferroptosis induced by RSL3 and Erastin, while inhibition of LUCAT1 expression reduced cell proliferation and increased ferroptosis. Mechanistically, downregulation of LUCAT1 resulted in the downregulation of both GTP cyclohydrolase 1 (GCH1) and ferroptosis suppressor protein 1 (FSP1). Furthermore, inhibition of LUCAT1 expression upregulated microRNA (miR)­34a­5p and then downregulated GCH1. These results indicated that inhibition of LUCAT1 expression promoted ferroptosis by modulating the downregulation of GCH1, mediated by miR­34a­5p. Therefore, the combination of knocking down LUCAT1 expression with ferroptosis inducers may be a promising strategy for lung cancer treatment.


Subject(s)
Down-Regulation , Ferroptosis , GTP Cyclohydrolase , Gene Expression Regulation, Neoplastic , Lung Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , Ferroptosis/genetics , MicroRNAs/genetics , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , A549 Cells , GTP Cyclohydrolase/genetics , GTP Cyclohydrolase/metabolism , Cell Proliferation , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , Male , Cell Line, Tumor , Female , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/metabolism
10.
Article in English | MEDLINE | ID: mdl-38785131

ABSTRACT

OBJECTIVE: This study aims to investigate the mechanism of Huangqin Tang in treating liver cancer. METHODS: Active ingredients and corresponding targets of Huangqin Tang were obtained from the Traditional Chinese Medicine Systems Pharmacology Database. Differentially expressed genes in liver cancer were identified from mRNA expression data. A protein-protein interaction (PPI) network was constructed using differentially expressed genes and Huangqin Tang targets. Random walk with restart (RWR) analysis was performed on the PPI network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted. A drug-active ingredient-gene interaction network was established, and molecular docking and molecular dynamics simulations were performed. Finally, the stability of binding between CDK1 and oroxylin was tested according to cellular thermal shift assay (CETSA). RESULTS: 160 active ingredients, 239 targets, and 1093 differentially expressed genes were identified. RWR analysis identified 10 potential targets for liver cancer. Enrichment analysis revealed protein kinase regulator activity and Steroid hormone biosynthesis as significant pathways. Molecular docking suggested a stable complex between oroxylin A and CDK1. CETSA demonstrated that the combination of oroxylin A and CDK1 increased the stability of CDK1, and the combination efficiency was high. CONCLUSION: Huangqin Tang may treat liver cancer by targeting CDK1 with oroxylin A. Protein kinase regulator activity and Steroid hormone biosynthesis pathways may play a role in liver cancer treatment with Huangqin Tang. This study provides insight into the mechanistic basis of Huangqin Tang for liver cancer treatment.

11.
Neurosurg Rev ; 47(1): 212, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38727935

ABSTRACT

We aimed to evaluate the relationship between imaging features, therapeutic responses (comparative cross-product and volumetric measurements), and overall survival (OS) in pediatric diffuse intrinsic pontine glioma (DIPG). A total of 134 patients (≤ 18 years) diagnosed with DIPG were included. Univariate and multivariate analyses were performed to evaluate correlations of clinical and imaging features and therapeutic responses with OS. The correlation between cross-product (CP) and volume thresholds in partial response (PR) was evaluated by linear regression. The log-rank test was used to compare OS patients with discordant therapeutic response classifications and those with concordant classifications. In univariate analysis, characteristics related to worse OS included lower Karnofsky, larger extrapontine extension, ring-enhancement, necrosis, non-PR, and increased ring enhancement post-radiotherapy. In the multivariate analysis, Karnofsky, necrosis, extrapontine extension, and therapeutic response can predict OS. A 25% CP reduction (PR) correlated with a 32% volume reduction (R2 = 0.888). Eight patients had discordant therapeutic response classifications according to CP (25%) and volume (32%). This eight patients' median survival time was 13.0 months, significantly higher than that in the non-PR group (8.9 months), in which responses were consistently classified as non-PR based on CP (25%) and volume (32%). We identified correlations between imaging features, therapeutic responses, and OS; this information is crucial for future clinical trials. Tumor volume may represent the DIPG growth pattern more accurately than CP measurement and can be used to evaluate therapeutic response.


Subject(s)
Brain Stem Neoplasms , Diffuse Intrinsic Pontine Glioma , Humans , Brain Stem Neoplasms/diagnostic imaging , Brain Stem Neoplasms/therapy , Brain Stem Neoplasms/mortality , Brain Stem Neoplasms/pathology , Male , Child , Female , Adolescent , Diffuse Intrinsic Pontine Glioma/therapy , Child, Preschool , Treatment Outcome , Magnetic Resonance Imaging , Infant , Retrospective Studies , Glioma/therapy , Glioma/pathology , Glioma/diagnostic imaging , Glioma/mortality
12.
Front Cardiovasc Med ; 11: 1345186, 2024.
Article in English | MEDLINE | ID: mdl-38745759

ABSTRACT

Background: Cardiometabolic disease is skyrocketing to epidemic proportions due to the high prevalence of its components and the aging of the worldwide population. More efforts are needed to improve cardiometabolic health. The aim of this nationally representative study based on the China Health and Retirement Longitudinal Study (CHARLS, 2014-2018) was to examine the association between reproductive factors and cardiometabolic disease among Chinese women aged ≥45 years. Methods: The CHARLS is an ongoing longitudinal study initiated in 2011, and the latest follow-up was completed in 2018. In total, 6,407 participants were analyzed. Effect-sizes are expressed as odds ratios (OR) and 95% confidence intervals (CI). Confounding was considered from statistical adjustment, subsidiary exploration, and unmeasured confounding assessment aspects. Results: Of 6,407 accessible participants, 60.9% were recorded as having one or more of five predefined cardiovascular or metabolic disorders. Compared to those with two children, participants who had 0-1 child were found to have a lower risk of cardiometabolic disease (OR = 0.844, 95% CI: 0.714-0.998), and those who had ≥3 children had a greater risk (OR = 1.181, 95% CI: 1.027-1.357). Age at menarche of 16-18 years was a protective factor compared with ≤16 years of age (OR = 0.858, 95% CI: 0.749-0.982). In contrast, participants with a history of abortion were 1.212 times more likely to have cardiometabolic disorders (OR = 1.212, 95% CI: 1.006-1.465). The likelihood for the presence of unmeasured confounding was low, as reflected by E-values. Conclusions: Our findings demonstrate that number of children, age at menarche, and history of abortion were associated with a significant risk of cardiometabolic disease among Chinese women aged ≥45 years.

13.
Waste Manag ; 185: 43-54, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38820783

ABSTRACT

Plastics within municipal solid waste (MSW) are non-degradable. As MSW continues to degrade, the relative content of plastics rises, and particle gradation may also change. Moreover, throughout the landfilling process, MSW is subjected to various stress conditions, potentially influencing its mechanical properties. This study explored the effects of varying plastic contents, different particle gradations, and distinct stress paths on the mechanical properties of MSW, and consolidated drained triaxial tests of 42 groups of reconstituted MSW specimens were conducted. The results showed that there was an optimal plastic content of 6-9 % for MSW, where the shear strength of MSW was higher than that of MSW with other plastic contents. When the stress path changed from TC45 to TC72, the optimal plastic content of MSW changed from 6 % to 9 %. As the plastic content increased, both the cohesion and internal friction angle of the MSW initially increased, then subsequently decreased. The impact of plastic content on cohesion was more pronounced than on the internal friction angle, especially at larger strains. Under various stress paths, MSW with distinct particle size distributions demonstrated diverse stress-strain behaviors. Traditional criteria for evaluating well-graded conditions in soils are not suitable for MSW. The effect of gradation on the cohesion of MSW is essentially due to the predominant role of fiber content; the relationship between gradation and the internal friction angle in MSW is complex and correlates closely with the content of both coarse and fine particles, as well as fibers. This study serves as an essential reference for predicting deformations in landfills and analyzing the stability of landfill slopes.

14.
Nat Commun ; 15(1): 4610, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816417

ABSTRACT

NLR family proteins act as intracellular receptors. Gene duplication amplifies the number of NLR genes, and subsequent mutations occasionally provide modifications to the second gene that benefits immunity. However, evolutionary processes after gene duplication and functional relationships between duplicated NLRs remain largely unclear. Here, we report that the rice NLR protein Pit1 is associated with its paralogue Pit2. The two are required for the resistance to rice blast fungus but have different functions: Pit1 induces cell death, while Pit2 competitively suppresses Pit1-mediated cell death. During evolution, the suppression of Pit1 by Pit2 was probably generated through positive selection on two fate-determining residues in the NB-ARC domain of Pit2, which account for functional differences between Pit1 and Pit2. Consequently, Pit2 lost its plasma membrane localization but acquired a new function to interfere with Pit1 in the cytosol. These findings illuminate the evolutionary trajectory of tandemly duplicated NLR genes after gene duplication.


Subject(s)
Gene Duplication , NLR Proteins , Oryza , Plant Proteins , NLR Proteins/genetics , NLR Proteins/metabolism , Oryza/genetics , Oryza/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Evolution, Molecular , Plant Diseases/microbiology , Plant Diseases/genetics , Plant Diseases/immunology , Disease Resistance/genetics , Cell Death , Phylogeny , Gene Expression Regulation, Plant
15.
Nat Cell Biol ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714852

ABSTRACT

Upon endoplasmic reticulum (ER) stress, activation of the ER-resident transmembrane protein kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1) initiates a key branch of the unfolded protein response (UPR) through unconventional splicing generation of the transcription factor X-box-binding protein 1 (XBP1s). Activated IRE1 can form large clusters/foci, whose exact dynamic architectures and functional properties remain largely elusive. Here we report that, in mammalian cells, formation of IRE1α clusters is an ER membrane-bound phase separation event that is coupled to the assembly of stress granules (SGs). In response to different stressors, IRE1α clusters are dynamically tethered to SGs at the ER. The cytosolic linker portion of IRE1α possesses intrinsically disordered regions and is essential for its condensation with SGs. Furthermore, disruption of SG assembly abolishes IRE1α clustering and compromises XBP1 mRNA splicing, and such IRE1α-SG coalescence engenders enrichment of the biochemical components of the pro-survival IRE1α-XBP1 pathway during ER stress. Our findings unravel a phase transition mechanism for the spatiotemporal assembly of IRE1α-SG condensates to establish a more efficient IRE1α machinery, thus enabling higher stress-handling capacity.

16.
World J Surg Oncol ; 22(1): 128, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38725005

ABSTRACT

BACKGROUND: N6-methyladenosine (m6A) modification plays an important role in lung cancer. However, methyltransferase-like 14 (METTL14), which serves as the main component of the m6A complex, has been less reported to be involved in the immune microenvironment of lung cancer. This study aimed to analyze the relationship between METTL14 and the immune checkpoint inhibitor programmed death receptor 1 (PD-1) in lung cancer. METHODS: CCK-8, colony formation, transwell, wound healing, and flow cytometry assays were performed to explore the role of METTL14 in lung cancer progression in vitro. Furthermore, syngeneic model mice were treated with sh-METTL14 andan anti-PD-1 antibody to observe the effect of METTL14 on immunotherapy. Flow cytometry and immunohistochemical (IHC) staining were used to detect CD8 expression. RIP and MeRIP were performed to assess the relationship between METTL14 and HSD17B6. LLC cells and activated mouse PBMCs were cocultured in vitro to mimic immune cell infiltration in the tumor microenvironment. ELISA was used to detect IFN-γ and TNF-α levels. RESULTS: The online database GEPIA showed that high METTL14 expression indicated a poor prognosis in patients with lung cancer. In vitro assays suggested that METTL14 knockdown suppressed lung cancer progression. In vivo assays revealed that METTL14 knockdown inhibited tumor growth and enhanced the response to PD-1 immunotherapy. Furthermore, METTL14 knockdown enhanced CD8+T-cell activation and infiltration. More importantly, METTL14 knockdown increased the stability of HSD17B6 mRNA by reducing its m6A methylation. In addition, HSD17B6 overexpression promoted the activation of CD8+ T cells. CONCLUSION: The disruption of METTL14 contributed to CD8+T-cell activation and the immunotherapy response to PD-1 via m6A modification of HSD17B6, thereby suppressing lung cancer progression.


Subject(s)
CD8-Positive T-Lymphocytes , Immune Checkpoint Inhibitors , Lung Neoplasms , Methyltransferases , Programmed Cell Death 1 Receptor , Tumor Microenvironment , Animals , Female , Mice , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Cell Proliferation , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/methods , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Lymphocyte Activation , Methyltransferases/metabolism , Methyltransferases/genetics , Mice, Inbred C57BL , Prognosis , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolism , Tumor Cells, Cultured , Tumor Microenvironment/immunology
17.
J Org Chem ; 89(11): 7812-7820, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38779840

ABSTRACT

In this paper, the regioselectivity of electrochemical Co(II)-catalyzed [2 + 2 + 2] cycloaddition of terminal alkynes was investigated using density functional theory. We explored in detail the energy profiles for both 1,2,4- and 1,3,5-regioselectivity pathways and revealed the origin of the regioselectivity. Two kinds of conformational isomers derived from the different coordination modes of alkynes with cobaltacyclopentadiene have been found, which were formed through electrochemically mediated redox processes. The regioselectivity of the reaction depends on the two coordination modes. When the Co(II) center attacks α-C of the third alkyne, while ß2-C in cyclopentadiene bonds to ß-C of the alkyne, the reaction favors the formation of 1,2,4-products. In contrast, when the Co(II) center connects to ß-C of the alkyne, it forms only the 1,3,5-products via [4 + 2] cycloaddition because of the steric repulsion between the bulky ligand on Co(II) and the phenyl group in the alkyne.

18.
Int J Ophthalmol ; 17(3): 596-602, 2024.
Article in English | MEDLINE | ID: mdl-38721520

ABSTRACT

AIM: To explore the clinical efficacy and safety of stromal lenticule addition keratoplasty (SLAK) with corneal crosslinking (CXL) on patients with corneal ectasia secondary to femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS: A series of 5 patients undertaking SLAK with CXL for the treatment of corneal ectasia secondary to FS-LASIK were followed for 4-9mo. The lenticules were collected from patients undertaking small incision lenticule extraction (SMILE) for the correction of myopia. Adding a stromal lenticule was aimed at improving the corneal thickness for the safe application of crosslinking and compensating for the thin cornea to improve its mechanical strength. RESULTS: All surgeries were conducted successfully with no significant complications. Their best corrected visual acuity (BCVA) ranged from 0.05 to 0.8-2 before surgery. The pre-operational total corneal thickness ranged from 345-404 µm and maximum keratometry (Kmax) ranged from 50.8 to 86.3. After the combination surgery, both the corneal keratometry (range 55.9 to 92.8) and total corneal thickness (range 413-482 µm) significantly increased. Four out of 5 patients had improvement of corneal biomechanical parameters (reflected by stiffness parameter A1 in Corvis ST). However, 3 patients showed decreased BCVA after surgery due to the development of irregular astigmatism and transient haze. Despite the onset of corneal edema right after SLAK, the corneal topography and thickness generally stabilized after 3mo. CONCLUSION: SLAK with CXL is a potentially beneficial and safe therapy for advanced corneal ectasia. Future work needs to address the poor predictability of corneal refractometry and compare the outcomes of different surgical modes.

19.
Diabetes Metab Syndr Obes ; 17: 2021-2026, 2024.
Article in English | MEDLINE | ID: mdl-38765469

ABSTRACT

Pseudohypoparathyroidism (PHP) is a rare genetic disease characterized by hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH) in serum. Here, we report a case of a patient with pseudohypoparathyroidism type IB (PHPIB) and subclinical hypothyroidism, analyze the clinical and genetic data of his family members, review the relevant literature, and classify and discuss the pathogenesis and clinical characteristics of each subtype. Finally, we discuss the treatment approach to improve clinicians' understanding of the disease.

20.
Article in English | MEDLINE | ID: mdl-38771418

ABSTRACT

PURPOSE: Intraoperative reconstruction of endoscopic scenes is a key technology for surgical navigation systems. The accuracy and efficiency of 3D reconstruction directly determine the effectiveness of navigation systems in a variety of clinical applications. While current deformable SLAM algorithms can meet real-time requirements, their underlying reliance on regular templates still makes it challenging to efficiently capture abrupt geometric features within scenes, such as organ contours and surgical margins. METHODS: We propose a novel real-time monocular deformable SLAM algorithm with geometrically adapted template. To ensure real-time performance, the proposed algorithm consists of two threads: a deformation mapping thread updates the template at keyframe rate and a deformation tracking thread estimates the camera pose and the deformation at frame rate. To capture geometric features more efficiently, the algorithm first detects salient edge features using a pre-trained contour detection network and then constructs the template through a triangulation method with guidance of the salient features. RESULTS: We thoroughly evaluated this method on Mandala and Hamlyn datasets in terms of accuracy and performance. The results demonstrated that the proposed method achieves better accuracy with 0.75-7.95% improvement and achieves consistent effectiveness in data association compared with the closest method. CONCLUSION: This study verified an adaptive template does improve the performance of reconstruction of dynamic laparoscopic Scenes with abrupt geometric features. However, further exploration is needed for applications in laparoscopic surgery with incisal margins caused by surgical instruments. This research serves as a crucial step toward enhanced automatic computer-assisted navigation in laparoscopic surgery. Code is available at https://github.com/Tang257/SLAM-with-geometrically-adapted-template .

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