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2.
bioRxiv ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38826355

ABSTRACT

An "induced PARP inhibitor (PARPi) sensitivity by epigenetic modulation" strategy is being evaluated in the clinic to sensitize homologous recombination (HR)-proficient tumors to PARPi treatments. To expand its clinical applications and identify more efficient combinations, we performed a drug screen by combining PARPi with 74 well-characterized epigenetic modulators that target five major classes of epigenetic enzymes. Both type I PRMT inhibitor and PRMT5 inhibitor exhibit high combination and clinical priority scores in our screen. PRMT inhibition significantly enhances PARPi treatment-induced DNA damage in HR-proficient ovarian and breast cancer cells. Mechanistically, PRMTs maintain the expression of genes associated with DNA damage repair and BRCAness and regulate intrinsic innate immune pathways in cancer cells. Analyzing large-scale genomic and functional profiles from TCGA and DepMap further confirms that PRMT1, PRMT4, and PRMT5 are potential therapeutic targets in oncology. Finally, PRMT1 and PRMT5 inhibition act synergistically to enhance PARPi sensitivity. Our studies provide a strong rationale for the clinical application of a combination of PRMT and PARP inhibitors in patients with HR-proficient ovarian or breast cancer.

3.
Nat Commun ; 15(1): 4675, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824139

ABSTRACT

H2O dissociation plays a crucial role in solar-driven catalytic CO2 methanation, demanding high temperature even for solar-to-chemical conversion efficiencies <1% with modest product selectivity. Herein, we report an oxygen-vacancy (Vo) rich CeO2 catalyst with single-atom Ni anchored around its surface Vo sites by replacing Ce atoms to promote H2O dissociation and achieve effective photothermal CO2 reduction under concentrated light irradiation. The high photon flux reduces the apparent activation energy for CH4 production and prevents Vo from depletion. The defects coordinated with single-atom Ni, significantly promote the capture of charges and local phonons at the Ni d-impurity orbitals, thereby inducing more effective H2O activation. The catalyst presents a CH4 yield of 192.75 µmol/cm2/h, with a solar-to-chemical efficiency of 1.14% and a selectivity ~100%. The mechanistic insights uncovered in this study should help further the development of H2O-activating catalysts for CO2 reduction and thereby expedite the practical utilization of solar-to-chemical technologies.

4.
Ann Surg Oncol ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833055

ABSTRACT

BACKGROUND: The management of Bismuth-Corlette type IV hilar cholangiocarcinoma typically necessitates extensive hepatectomy, resection of the extrahepatic bile ducts, regional lymph node dissection, and reconstruction of the biliary tract; however, there is a high incidence of postoperative liver dysfunction and failure. METHODS: A 64-year-old male patient was admitted to our department after 1 month of escalating jaundice and abdominal discomfort. Upon admission, his total bilirubin was 334 µmol/L and his direct bilirubin was 221 µmol/L. His carbohydrate antigen 19-9 was > 1200.00 U/mL, his carcinoembryonic antigen was 98.90 U/mL, and his α-fetoprotein was normal. Enhanced computed tomography (CT) and magnetic resonance imaging scans revealed a thickened and enlarged biliary tree extending from the common hepatic duct to the orifices of the left and right hepatic ducts. RESULTS: The patient underwent total laparoscopic radical resection of S1 + S4, accompanied by radical lymphadenectomy with skeletonization and biliary reconstruction. The surgery was successfully conducted within 450 min, with a minimal blood loss of 200 mL. The histological grading was T2bN1M0 (stage III). CT on postoperative day 5 showed satisfactory postoperative recovery. The patient was discharged from the hospital on postoperative day 10 without complications, following which the patient underwent a regimen of single-agent capecitabine chemotherapy. Over a 20-month follow-up period, no recurrence was observed. CONCLUSIONS: Resection of hepatic segments S1 + S4 is a viable surgical option for hilar carcinoma in cases with poor liver function or when the carcinoma is confined to both hepatic ducts without invasion of the hepatic artery and portal vein.

5.
Clin Breast Cancer ; 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38729821

ABSTRACT

BACKGROUND: Approximately 30% to 50% of patients with human epidermal growth factor receptor 2-positive metastatic breast cancer develop brain metastasis (BMs). Pyrotinib has shown promising efficacy in these patients. However, real-world evidence supporting its use is scarce. Therefore, we evaluate the efficacy and safety of pyrotinib-based regimens in the real world. MATERIALS AND METHODS: We enrolled patients with BMs from various healthcare facilities in China's Shandong region and used an updated breast-graded prognostic assessment (breast-GPA) to predict survival outcomes. RESULTS: Efficacy and toxicity were assessed in 101 patients. Overall, the median progression-free survival (PFS) was 11.0 months (95% CI, 7.6-14.4 months). PFS was shorter in patients with a breast-GPA of 0 to 2.0 (P< .001). Previous treatment with pertuzumab plus trastuzumab (P = .039) and varying numbers of BMs (P = .028) had a significant positive correlation with PFS. Additionally, radiotherapy (P = .033) for BMs, especially pyrotinib concurrent with radiotherapy (P = .013), significantly prolonged the PFS. In patients with a breast-GPA of 0 to 2.0, a significant difference in PFS was observed depending on whether the brain was the first metastatic site (P< .001). Furthermore, a breast-GPA (0-2.0 vs. 2.5-4.0), and radiotherapy for BMs were found to be independent predictors of PFS. Overall, the objective response rate was 42.6%, while the disease control rate was 88.1%. Diarrhea emerged as the most common adverse event. CONCLUSION: Pyrotinib-based therapy is effective and tolerable in human epidermal growth factor receptor 2-positive metastatic breast cancer with BMs. Patients who underwent radiotherapy for BMs, particularly those who received pyrotinib concurrently with radiotherapy, exhibited a more favorable prognosis.

7.
BMC Med Res Methodol ; 24(1): 105, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702624

ABSTRACT

BACKGROUND: Survival prediction using high-dimensional molecular data is a hot topic in the field of genomics and precision medicine, especially for cancer studies. Considering that carcinogenesis has a pathway-based pathogenesis, developing models using such group structures is a closer mimic of disease progression and prognosis. Many approaches can be used to integrate group information; however, most of them are single-model methods, which may account for unstable prediction. METHODS: We introduced a novel survival stacking method that modeled using group structure information to improve the robustness of cancer survival prediction in the context of high-dimensional omics data. With a super learner, survival stacking combines the prediction from multiple sub-models that are independently trained using the features in pre-grouped biological pathways. In addition to a non-negative linear combination of sub-models, we extended the super learner to non-negative Bayesian hierarchical generalized linear model and artificial neural network. We compared the proposed modeling strategy with the widely used survival penalized method Lasso Cox and several group penalized methods, e.g., group Lasso Cox, via simulation study and real-world data application. RESULTS: The proposed survival stacking method showed superior and robust performance in terms of discrimination compared with single-model methods in case of high-noise simulated data and real-world data. The non-negative Bayesian stacking method can identify important biological signal pathways and genes that are associated with the prognosis of cancer. CONCLUSIONS: This study proposed a novel survival stacking strategy incorporating biological group information into the cancer prognosis models. Additionally, this study extended the super learner to non-negative Bayesian model and ANN, enriching the combination of sub-models. The proposed Bayesian stacking strategy exhibited favorable properties in the prediction and interpretation of complex survival data, which may aid in discovering cancer targets.


Subject(s)
Bayes Theorem , Genomics , Neoplasms , Humans , Neoplasms/genetics , Neoplasms/mortality , Genomics/methods , Prognosis , Algorithms , Proportional Hazards Models , Neural Networks, Computer , Survival Analysis , Computational Biology/methods
8.
Mitochondrial DNA B Resour ; 9(5): 616-620, 2024.
Article in English | MEDLINE | ID: mdl-38737393

ABSTRACT

Tylopilus brunneirubens is a common species in southern China. It is known for brown to dark brown pileus, white context turning reddish brown or rust brown when touched and distinct reticulation on the upper stem. However, little is known about its mitochondrial genome and its relationship with other boletes. Our analysis revealed that the mitochondrial genome of this species is a circular DNA molecule that spans 32,389 bp. It contains 15 core protein-coding genes, 24 transfer RNA genes, and two ribosomal RNA genes. The base composition of the mitochondrial genome is as follows: A (37.20%), C (11.32%), G (12.48%), and T (39.00%), with a GC content of 23.80%. Furthermore, a phylogenetic tree based on 24 mitochondrial genomes provided valuable insights into the phylogenetic relationships of Tylopilus brunneirubens with other boletes for the first time.

9.
J Agric Food Chem ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38757388

ABSTRACT

This study extensively characterized yeast polysaccharides (YPs) from Pichia fermentans (PF) and Pichia kluyveri (PK), with a specific focus on their structural attributes and their interaction with wine fruity esters in a model wine system. By finely tuning enzymatic reactions based on temperature, pH, and enzyme dosage, an optimal YP yield of 77.37% was achieved, with a specific mass ratio of cellulase, pectinase, and protease set at 3:5:2. There were four YP fractions (YPPF-W, YPPF-N, YPPK-W, and YPPK-N) isolated from the two yeasts. YPPF-N and YPPK-N were identified as glucans based on monosaccharide analysis and Fourier-transform infrared spectroscopy analysis. "Specific degradation-methylation-nuclear magnetic" elucidated YPPF-W's backbone structure as 1,3-linked α-l-Man and 1,6-linked α-d-Glc residues, while YPPK-W displayed a backbone structure of 1,3-linked α-Man residues, indicative of a mannoprotein nature. Isothermal titration calorimetry revealed spontaneous interactions between YPPK-W/YPPF-W and fruity esters across temperatures (25-45 °C), with the strongest interaction observed at 30 °C. However, distinct esters exhibited varying interactions with YPPK-W and YPPF-W, attributed to differences in molecular weights and hydrophobic characteristics. While shedding light on these intricate interactions, further experimental data is essential for a comprehensive understanding of yeast polysaccharides' or mannoproteins' impact on fruity esters. This research significantly contributes to advancing our knowledge of yeast polysaccharides' role in shaping the nuanced sensory attributes of wine.

10.
Article in English | MEDLINE | ID: mdl-38752993

ABSTRACT

Two novel bacterial strains, designated as SYSU D00823T and SYSU D00873T, were isolated from sandy soil of the Gurbantunggut Desert in Xinjiang, north-west China. SYSU D00823T and SYSU D00873T shared 99.0 % 16S rRNA gene sequence identity, and were both most closely related to Pedobacter xinjiangensis 12157T with 96.1 % and 96.0 % similarities, respectively. Phylogenetic and phylogenomic analyses revealed that the two isolates and P. xinjiangensis 12157T formed a separate distinct cluster in a stable subclade with the nearby species Pedobacter mongoliensis 1-32T, as well as the genera Pararcticibacter and Arcticibacter. Furthermore, P. mongoliensis 1-32T formed a separate deep-branching lineage and did not form a cluster with members of the genus Pedobacter. The average nucleotide identity and digital DNA-DNA hybridization values between SYSU D00823T and SYSU D00873T and related species were well below the thresholds for species delineation (<81.0 % and <24.0 %, respectively). The genomes of SYSU D00823T and SYSU D00873T were 6.19 and 6.43 Mbp in size with 40.4 % and 40.5 % DNA G+C contents, respectively. The predominant fatty acids (>10 %) of SYSU D00823T and SYSU D00873T were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c). Menaquinone-7 was the only respiratory quinone. The major polar lipids were phosphatidylethanolamine, glycosphingolipid, aminoglycolipid/glycolipid, aminophospholipid and three or four unidentified polar lipids. These data indicated that strains SYSU D00823T and SYSU D00873T should be assigned to two novel species of a new genus within the family Sphingobacteriaceae, for which the names Desertivirga arenae gen. nov., sp. nov. and Desertivirga brevis sp. nov. are proposed. The type strains are SYSU D00823T (=CGMCC 1.18630T=MCCC 1K04973T=KCTC 82278T) and SYSU D00873T (=CGMCC 1.18629T=MCCC 1K04974T=KCTC 82281T), respectively. Accordingly, the reclassification of P. xinjiangensis as Desertivirga xinjiangensis comb. nov., and P. mongoliensis as Paradesertivirga mongoliensis gen. nov., comb. nov. are also proposed.


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Desert Climate , Fatty Acids , Pedobacter , Phylogeny , RNA, Ribosomal, 16S , Sequence Analysis, DNA , Soil Microbiology , Vitamin K 2 , RNA, Ribosomal, 16S/genetics , Pedobacter/genetics , Pedobacter/classification , Pedobacter/isolation & purification , Fatty Acids/chemistry , China , DNA, Bacterial/genetics , Vitamin K 2/analogs & derivatives , Nucleic Acid Hybridization
11.
Nat Biotechnol ; 2024 May 14.
Article in English | MEDLINE | ID: mdl-38744947

ABSTRACT

Cancer immunotherapy with autologous chimeric antigen receptor (CAR) T cells faces challenges in manufacturing and patient selection that could be avoided by using 'off-the-shelf' products, such as allogeneic CAR natural killer T (AlloCAR-NKT) cells. Previously, we reported a system for differentiating human hematopoietic stem and progenitor cells into AlloCAR-NKT cells, but the use of three-dimensional culture and xenogeneic feeders precluded its clinical application. Here we describe a clinically guided method to differentiate and expand IL-15-enhanced AlloCAR-NKT cells with high yield and purity. We generated AlloCAR-NKT cells targeting seven cancers and, in a multiple myeloma model, demonstrated their antitumor efficacy, expansion and persistence. The cells also selectively depleted immunosuppressive cells in the tumor microenviroment and antagonized tumor immune evasion via triple targeting of CAR, TCR and NK receptors. They exhibited a stable hypoimmunogenic phenotype associated with epigenetic and signaling regulation and did not induce detectable graft versus host disease or cytokine release syndrome. These properties of AlloCAR-NKT cells support their potential for clinical translation.

13.
Clin Transl Med ; 14(5): e1687, 2024 May.
Article in English | MEDLINE | ID: mdl-38738791

ABSTRACT

OBJECTIVE: It has been observed that the prognosis of patients with HER2-positive metastatic breast cancer has improved significantly with HER2-targeted agents. However, there is still a lack of evidence regarding first-line anti-HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti-HER2 treatment in these patients. METHODS: Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer were enrolled. Pyrotinib plus albumin-bound paclitaxel were used as first-line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. RESULTS: From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow-up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand-foot syndrome (3.7%). Toll-like receptor 3 (TLR3) and Proto-oncogene tyrosine-protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. CONCLUSIONS: This study demonstrates that pyrotinib plus albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.


Subject(s)
Breast Neoplasms , Receptor, ErbB-2 , Trastuzumab , Humans , Female , Breast Neoplasms/drug therapy , Middle Aged , Adult , Trastuzumab/therapeutic use , Trastuzumab/pharmacology , Prospective Studies , Aged , Receptor, ErbB-2/metabolism , Albumin-Bound Paclitaxel/therapeutic use , Albumin-Bound Paclitaxel/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Acrylamides/therapeutic use , Neoadjuvant Therapy/methods , Proto-Oncogene Mas , Sulfinic Acids/therapeutic use , Sulfinic Acids/pharmacology , Aminoquinolines/therapeutic use , Aminoquinolines/pharmacology , Treatment Outcome
14.
Circ Cardiovasc Qual Outcomes ; : e010457, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38779848

ABSTRACT

BACKGROUND: Noninvasive cardiac testing (NICT) has been associated with decreased long-term risks of major adverse cardiac events (MACEs) among emergency department patients at high coronary risk. It is unclear whether this association extends to patients without evidence of myocardial injury on initial ECG and cardiac troponin testing. METHODS: A retrospective cohort study was conducted of patients presenting with chest pain between 2013 and 2019 to 21 emergency departments within an integrated health care system in Northern California, excluding patients with ST-segment-elevation myocardial infarction or myocardial injury by serum troponin testing. To account for confounding by indication, we grouped patient encounters by the NICT referral rate of the initially assigned emergency physician relative to local peers within discrete time periods. The primary outcome was MACE within 2 years. Secondary outcomes were coronary revascularization and MACE, inclusive of all-cause mortality. Associations between the NICT referral group (low, intermediate, or high) and outcomes were assessed using risk-adjusted proportional hazards methods with censoring for competing events. RESULTS: Among 144 577 eligible patient encounters, the median age was 58 years (interquartile range, 48-68) and 57% were female. Thirty-day NICT referral was 13.0%, 19.9%, and 27.8% in low, intermediate, and high NICT referral groups, respectively, with a good balance of baseline covariates between groups. Compared with the low NICT referral group, there was no significant decrease in the adjusted hazard ratio of MACE within the intermediate (adjusted hazard ratio, 1.08 [95% CI, 1.02-1.14]) or high (adjusted hazard ratio, 1.05 [95% CI, 0.99-1.11]) NICT referral groups. Results were similar for MACE, inclusive of all-cause mortality, and coronary revascularization, as well as subgroup analyses stratified by estimated risk (history, electrocardiogram, age, risk factors, troponin [HEART] score: percent classified as low risk, 48.2%; moderate risk, 49.2%; and high risk, 2.7%). CONCLUSIONS: Increases in NICT referrals were not associated with changes in the hazard of MACE within 2 years following emergency department visits for chest pain without evidence of acute myocardial injury. These findings further highlight the need for evidence-based guidance regarding the appropriate use of NICT in this population.

15.
Sci Total Environ ; 935: 173172, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38740210

ABSTRACT

Chronic hypoxia can affect the growth and metabolism of fish and potentially impact gonadal development through epigenetic regulation. Trachinotus blochii (Golden pompano) is widely cultured near the coast and is sensitive to low oxygen conditions. We found that hypoxia and reoxygenation processes acted on multiple targets on the HPG axis, leading to endocrine disorders. Changes in the expression of key genes in the brain (gnrh), pituitary (fsh and lh), ovaries (cyp19a1a, foxl2, and er), and testes (dmrt1, ar, sox9, and gsdf) were associated with significant decreases in estrogen and testosterone levels. Hypoxia and reoxygenation lead to changes in DNA methylation levels in the gonads. Hypoxia upregulated the expression of dnmt1, dnmt3a, dnmt3b, tet1, and tet2 in females and dnmt3a and dnmt3b in males, while reoxygenation down-regulated the expression of dnmt1, dnmt3a, dnmt3b, tet1, and tet2 in males. Whole genome methylation sequencing showed that the number of differentially methylated regions was highest on chromosome 10 (5192) and lowest on chromosome 24 (275). Differentially methylated genes in females and males, as well as between males and females, were enriched in the oxytocin signaling pathway, fatty acid metabolism pathway, and HIF-1a pathway. In summary, hypoxia and reoxygenation can induce endocrine disorders, affect the expression of HPG axis genes, change the methylation pattern and modification pattern of gonad DNA, and then have potential effects on gonad development.

17.
ACS Nano ; 18(20): 13035-13048, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38728209

ABSTRACT

We report a solvothermal method for the synthesis of an oxygen vacancy-enriched ZrO2 photocatalyst with Co single atoms and Ni clusters immobilized on the surface. This catalyst presents superior performance for the reduction of CO2 in H2O vapor, with a CO yield reaching 663.84 µmol g-1 h-1 and a selectivity of 99.52%. The total solar-to-chemical energy conversion efficiency is up to 0.372‰, which is among the highest reported values. The success, on one hand, depends on the Co single atoms and Ni clusters for both extended spectrum absorption and serving as dual-active centers for CO2 reduction and H2O dissociation, respectively; on the other hand, this is attributed to the enhanced photoelectric and thermal effect induced by concentrated solar irradiation. We demonstrate that an intermediate impurity state is formed by the hybridization of the d-orbital of single-atom Co with the molecular orbital of H2O, enabling visible-light-driven excitation over the catalyst. In addition, Ni clusters play a crucial role in altering the adsorption configuration of CO2, with the localized surface plasmon resonance effect enhancing the activation and dissociation of CO2 induced by visible-near-infrared light. This study provides valuable insights into the synergistic effect of the dual cocatalyst toward both efficient photothermal coupling and surface redox reactions for solar CO2 reduction.

18.
ACS Omega ; 9(19): 21097-21115, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38764674

ABSTRACT

The lacustrine shale of the Shahezi Formation in the Songliao Basin has obvious organic matter enrichment characteristics and great potential for oil and gas resources. At present, the understanding of the sedimentary paleoenvironment and organic matter enrichment characteristics of the lacustrine shale of the Shahezi Formation is relatively weak. Therefore, taking the international continental scientific drilling Program (ICDP) borehole Songke-2 (SK-2) with continuous and whole Shahezi cores as the research object, combined with organic geochemistry, elemental geochemistry, and logging data, the sedimentary paleoenvironment and organic matter enrichment mechanism were studied. The results show that the organic matter of Shahezi shale is generally in the high to over mature stage. The kerogen type of organic matter is mainly II2-III. The organic matter is mainly derived from the lake basin's own algae and terrestrial higher plants. The total organic carbon (TOC) content of Shahezi shale is relatively high, and the TOC is mainly distributed between 1% and 2%. The Shahezi Formation is dominated by clay shale and siliceous shale, and experienced moderate chemical weathering during deposition. According to the analysis of organic geochemistry and elemental geochemistry data, the paleoenvironment of organic matter deposition in Shahezi shale was dominated by warm and humid climate in the early stage, and then experienced multiple cooling and arid periods. The climate type turned to semihumid-semiarid, with stable terrigenous debris input, low deposition rate, brackish water salinity and oxygen-rich-oxygen-poor water environment. The sedimentary period of Shahezi Formation is in the Cretaceous oceanic anoxic Aptian-Albian stage. During the oceanic anoxic event, the anoxic sedimentary environment and the frequent volcanic activity have an important impact on the organic matter enrichment. The oceanic anoxic event and volcanic activity are the main causes of water body hypoxia in the lake basin. The nutrients brought by volcanic activity are also one of the reasons for promoting the growth of lake basin organisms, creating good conditions for organic matter enrichment. The enrichment of organic matter in Shahezi Formation is the result of the interaction and coupling of various factors such as paleoclimate, paleoenvironment, paleoproductivity, water environment, terrestrial input, and major geological events. And, the organic matter enrichment model of Shahezi Formation shale is established.

19.
Sensors (Basel) ; 24(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38732805

ABSTRACT

The global reliance on oil and gas pipelines for energy transportation is increasing. As the pioneering review in the field of ultrasonic defect detection for oil and gas pipelines based on bibliometric methods, this study employs visual analysis to identify the most influential countries, academic institutions, and journals in this domain. Through cluster analysis, it determines the primary trends, research hotspots, and future directions in this critical field. Starting from the current global industrial ultrasonic in-line inspection (ILI) detection level, this paper provides a flowchart for selecting detection methods and a table for defect comparison, detailing the comparative performance limits of different detection devices. It offers a comprehensive perspective on the latest ultrasonic pipeline detection technology from laboratory experiments to industrial practice.

20.
J Biomed Res ; : 1-11, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38807375

ABSTRACT

Meiotic resumption in mammalian oocytes involves nucleus and organelle structural changes, notably chromatin configuration transitioning from non-surrounding nucleolus (NSN) to surrounding nucleolus (SN) in germinal vesicle (GV) oocytes. Our study found that nuclear speckles, a subnuclear structure mainly composed of serine-arginine (SR) proteins, changed from a diffuse spotted distribution in mouse NSN oocytes to an aggregation pattern in SN oocytes. We further discovered that SRPK1, an enzyme phosphorylating SR proteins, co-localized with NS at SN stage and NSN oocytes failed to convert into SN oocytes after inhibiting the activity of SRPK1. Furthermore, the typical structure of chromatin ring around the nucleolus in SN oocytes collapsed after inhibitor treatment. To explore the underlying mechanism, phosphorylated SR proteins were confirmed to be associated with chromatin by salt extraction experiment, and in situ DNase I assay showed that the accessibility of chromatin enhanced in SN oocytes with SRPK1 inhibited, accompanied by decreased repressive modification on histone and abnormal recurrence of transcriptional signal. In conclusion, our results indicated that SRPK1-regulated phosphorylation on SR proteins was involved in the NSN to SN transition and played an important role in maintaining the condensation nucleus of SN oocytes via interacting with chromatin.

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