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1.
Cell ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38971151

ABSTRACT

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.

2.
Cell ; 186(25): 5517-5535.e24, 2023 12 07.
Article in English | MEDLINE | ID: mdl-37992713

ABSTRACT

Transfer RNA (tRNA) modifications are critical for protein synthesis. Queuosine (Q), a 7-deaza-guanosine derivative, is present in tRNA anticodons. In vertebrate tRNAs for Tyr and Asp, Q is further glycosylated with galactose and mannose to generate galQ and manQ, respectively. However, biogenesis and physiological relevance of Q-glycosylation remain poorly understood. Here, we biochemically identified two RNA glycosylases, QTGAL and QTMAN, and successfully reconstituted Q-glycosylation of tRNAs using nucleotide diphosphate sugars. Ribosome profiling of knockout cells revealed that Q-glycosylation slowed down elongation at cognate codons, UAC and GAC (GAU), respectively. We also found that galactosylation of Q suppresses stop codon readthrough. Moreover, protein aggregates increased in cells lacking Q-glycosylation, indicating that Q-glycosylation contributes to proteostasis. Cryo-EM of human ribosome-tRNA complex revealed the molecular basis of codon recognition regulated by Q-glycosylations. Furthermore, zebrafish qtgal and qtman knockout lines displayed shortened body length, implying that Q-glycosylation is required for post-embryonic growth in vertebrates.


Subject(s)
RNA, Transfer , Animals , Humans , Rats , Anticodon , Cell Line , Codon , Glycosylation , Nucleoside Q/chemistry , Nucleoside Q/genetics , Nucleoside Q/metabolism , RNA, Transfer/chemistry , RNA, Transfer/metabolism , Swine , Zebrafish/metabolism , Nucleic Acid Conformation
3.
Nature ; 589(7842): 396-401, 2021 01.
Article in English | MEDLINE | ID: mdl-33473229

ABSTRACT

The water-gas shift (WGS) reaction is an industrially important source of pure hydrogen (H2) at the expense of carbon monoxide and water1,2. This reaction is of interest for fuel-cell applications, but requires WGS catalysts that are durable and highly active at low temperatures3. Here we demonstrate that the structure (Pt1-Ptn)/α-MoC, where isolated platinum atoms (Pt1) and subnanometre platinum clusters (Ptn) are stabilized on α-molybdenum carbide (α-MoC), catalyses the WGS reaction even at 313 kelvin, with a hydrogen-production pathway involving direct carbon monoxide dissociation identified. We find that it is critical to crowd the α-MoC surface with Pt1 and Ptn species, which prevents oxidation of the support that would cause catalyst deactivation, as seen with gold/α-MoC (ref. 4), and gives our system high stability and a high metal-normalized turnover number of 4,300,000 moles of hydrogen per mole of platinum. We anticipate that the strategy demonstrated here will be pivotal for the design of highly active and stable catalysts for effective activation of important molecules such as water and carbon monoxide for energy production.

4.
FASEB J ; 38(10): e23698, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38780613

ABSTRACT

Prostate cancer (PCa) is a widespread global health concern characterized by elevated rates of occurrence, and there is a need for novel therapeutic targets to enhance patient outcomes. FOXS1 is closely linked to different cancers, but its function in PCa is still unknown. The expression of FOXS1, its prognostic role, clinical significance in PCa, and the potential mechanism by which FOXS1 affects PCa progression were investigated through bioinformatics analysis utilizing public data. The levels of FOXS1 and HILPDA were evaluated in clinical PCa samples using various methods, such as western blotting, immunohistochemistry, and qRT-PCR. To examine the function and molecular mechanisms of FOXS1 in PCa, a combination of experimental techniques including CCK-8 assay, flow cytometry, wound-healing assay, Transwell assay, and Co-IP assay were employed. The FOXS1 expression levels were significantly raised in PCa, correlating strongly with tumor aggressiveness and an unfavorable prognosis. Regulating FOXS1 expression, whether upregulating or downregulating it, correspondingly enhanced or inhibited the growth, migration, and invasion capabilities of PCa cells. Mechanistically, we detected a direct interaction between FOXS1 and HILPDA, resulting in the pathway activation of FAK/PI3K/AKT and facilitation EMT in PCa cells. FOXS1 collaborates with HILPDA to initiate EMT, thereby facilitating the PCa progression through the FAK/PI3K/AKT pathway activation.


Subject(s)
Epithelial-Mesenchymal Transition , Forkhead Transcription Factors , Gene Expression Regulation, Neoplastic , Phosphatidylinositol 3-Kinases , Prostatic Neoplasms , Proto-Oncogene Proteins c-akt , Humans , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Prostatic Neoplasms/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Male , Forkhead Transcription Factors/metabolism , Forkhead Transcription Factors/genetics , Phosphatidylinositol 3-Kinases/metabolism , Cell Line, Tumor , Focal Adhesion Kinase 1/metabolism , Focal Adhesion Kinase 1/genetics , Signal Transduction , Up-Regulation , Cell Movement , Cell Proliferation , Animals , Mice , Oncogenes , Prognosis , Mice, Nude
5.
Lancet Oncol ; 25(1): 76-85, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38048802

ABSTRACT

BACKGROUND: Locally advanced cervical cancer constitutes around 37% of cervical cancer cases globally and has a poor prognosis due to limited therapeutic options. Immune checkpoint inhibitors in the neoadjuvant setting could address these challenges. We aimed to investigate the efficacy and safety of neoadjuvant chemo-immunotherapy for locally advanced cervical cancer. METHODS: In this single-arm, phase 2 trial, which was done across eight tertiary hospitals in China, we enrolled patients aged 18-70 years with untreated cervical cancer (IB3, IIA2, or IIB/IIIC1r with a tumour diameter ≥4 cm [International Federation of Gynecology and Obstetrics, 2018]) and an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible patients underwent one cycle of priming doublet chemotherapy (75-80 mg/m2 cisplatin, intravenously, plus 260 mg/m2 nab-paclitaxel, intravenously), followed by two cycles of a combination of chemotherapy (cisplatin plus nab-paclitaxel) on day 1 with camrelizumab (200 mg, intravenously) on day 2, with a 3-week interval between treatment cycles. Patients with stable disease or progressive disease received concurrent chemoradiotherapy, and patients with a complete response or partial response proceeded to radical surgery. The primary endpoint was the objective response rate, by independent central reviewer according to Response Evaluation Criteria in Solid Tumours, version 1.1. Activity and safety were analysed in patients who received at least one dose of camrelizumab. This study is registered with ClinicalTrials.gov, NCT04516616, and is ongoing. FINDINGS: Between Dec 1, 2020, and Feb 10, 2023, 85 patients were enrolled and all received at least one dose of camrelizumab. Median age was 51 years (IQR 46-57) and no data on race or ethnicity were collected. At data cutoff (April 30, 2023), median follow-up was 11·0 months (IQR 6·0-14·5). An objective response was noted in 83 (98% [95% CI 92-100]) patients, including 16 (19%) patients who had a complete response and 67 (79%) who had a partial response. The most common grade 3-4 treatment-related adverse events during neoadjuvant chemo-immunotherapy were lymphopenia (21 [25%] of 85), neutropenia (ten [12%]), and leukopenia (seven [8%]). No serious adverse events or treatment-related deaths occurred. INTERPRETATION: Neoadjuvant chemo-immunotherapy showed promising antitumour activity and a manageable adverse event profile in patients with locally advanced cervical cancer. The combination of neoadjuvant chemo-immunotherapy with radical surgery holds potential as a novel therapeutic approach for locally advanced cervical cancer. FUNDING: National Key Technology Research and Development Program of China and the National Clinical Research Center of Obstetrics and Gynecology.


Subject(s)
Thrombocytopenia , Uterine Cervical Neoplasms , Female , Humans , Middle Aged , Cisplatin/adverse effects , Neoadjuvant Therapy/adverse effects , Uterine Cervical Neoplasms/drug therapy , Antibodies, Monoclonal, Humanized/adverse effects , Thrombocytopenia/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effects
6.
J Am Chem Soc ; 146(4): 2711-2717, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38237137

ABSTRACT

The coconversion of two kinds of waste materials, plastics and CO2, into a single value-added product is an innovative and challenging endeavor that simultaneously achieves the upcycling of plastic waste and reduces CO2 emissions. Herein, we report a one-pot, two-step catalytic process for transforming polyesters, such as poly(glycolic acid), carbonate, and water, into sodium formate with a high yield of 79%, using a commercial Pd/C catalyst. This process involves the aqueous-phase reforming of polyester with water at 250-270 °C and the hydrogenation of NaHCO3 at 150 °C, utilizing H2 generated during the reforming process. Notably, no external H2 or other reactive reagents are required. This strategy can be applied for the coconversion of poly(ethylene terephthalate) (PET), poly(butylene-adipate-co-terephthalate) (PBAT), and commercial biodegradable plastic bags with Na2CO3 obtained from CO2 capture via a NaOH solution, opening up a new path for "turning trash into treasure".

7.
J Am Chem Soc ; 146(4): 2290-2307, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38236140

ABSTRACT

Strong metal-support interactions (SMSIs) have emerged as a significant and cutting-edge area of research in heterogeneous catalysis. They play crucial roles in modifying the chemisorption properties, interfacial structure, and electronic characteristics of supported metals, thereby exerting a profound influence on the catalytic properties. This Perspective aims to provide a comprehensive summary of the latest advancements and insights into SMSIs, with a focus on state-of-the-art in situ/operando characterization techniques. This overview also identifies innovative designs and applications of new types of SMSI systems in catalytic chemistry and highlights their pivotal role in enhancing catalytic performance, selectivity, and stability in specific cases. Particularly notable is the discovery of SMSI between active metals and metal carbides, which opens up a new era in the field of SMSI. Additionally, the strong interactions between atomically dispersed metals and supports are discussed, with an emphasis on the electronic effects of the support. The chemical nature of SMSI and its underlying catalytic mechanisms are also elaborated upon. It is evident that SMSI modification has become a powerful tool for enhancing catalytic performance in various catalytic applications.

8.
J Am Chem Soc ; 146(6): 3764-3772, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38304977

ABSTRACT

TiO2-supported Pt species have been widely applied in numerous critical reactions involving photo-, thermo-, and electrochemical-catalysis for decades. Manipulation of the state of the Pt species in Pt/TiO2 catalysts is crucial for fine-tuning their catalytic performance. Here, we report an interesting discovery showing the epitaxial growth of PtO2 atomic layers on rutile TiO2, potentially allowing control of the states of active Pt species in Pt/TiO2 catalysts. The presence of PtO2 atomic layers could modulate the geometric configuration and electronic state of the Pt species under reduction conditions, resulting in a spread of the particle shape and obtaining a Pt/PtO2/TiO2 structure with more positive valence of Pt species. As a result, such a catalyst exhibits exceptional electrocatalytic activity and stability toward hydrogen evolution reaction, while also promoting the thermocatalytic CO oxidation, surpassing the performance of the Pt/TiO2 catalyst with no epitaxial structure. This novel epitaxial growth of the PtO2 structure on rutile TiO2 in Pt/TiO2 catalysts shows its potential in the rational design of highly active and economical catalysts toward diverse catalytic reactions.

9.
J Am Chem Soc ; 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38592685

ABSTRACT

The determination of catalytically active sites is crucial for understanding the catalytic mechanism and providing guidelines for the design of more efficient catalysts. However, the complex structure of supported metal nanocatalysts (e.g., support, metal surface, and metal-support interface) still presents a big challenge. In particular, many studies have demonstrated that metal-support interfaces could also act as the primary active sites in catalytic reactions, which is well elucidated in oxide-supported metal nanocatalysts but is rarely reported in carbon-supported metal nanocatalysts. Here, we fill the above gap and demonstrate that metal-sulfur interfaces in sulfur-doped carbon-supported metal nanocatalysts are the primary active sites for several catalytic hydrogenation reactions. A series of metal nanocatalysts with similar sizes but different amounts of metal-sulfur interfaces were first constructed and characterized. Taking Ir for quinoline hydrogenation as an example, it was found that their catalytic activities were proportional to the amount of the Ir-S interface. Further experiments and density functional theory (DFT) calculations suggested that the adsorption and activation of quinoline occurred on the Ir atoms at the Ir-S interface. Similar phenomena were found in p-chloronitrobenzene hydrogenation over the Pt-S interface and benzoic acid hydrogenation over the Ru-S interface. All of these findings verify the predominant activity of metal-sulfur interfaces for catalytic hydrogenation reactions and contribute to the comprehensive understanding of metal-support interfaces in supported nanocatalysts.

10.
J Am Chem Soc ; 146(1): 1071-1080, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38157430

ABSTRACT

Strong metal-support interaction (SMSI) has been extensively studied in heterogeneous catalysis because of its significance in stabilizing active metals and tuning catalytic performance, but the origin of SMSI is not fully revealed. Herein, by using Pt/CeO2 as a model catalyst, we report an embedding structure at the interface between Pt and (110) plane of CeO2, where Pt clusters (∼1.6 nm) are embedded into the lattice of ceria within 3-4 atomic layers. In contrast, this phenomenon is absent in the CeO2(100) support. This unique geometric structure, as an effective motivator, triggers more significant electron transfer from Pt clusters to CeO2(110) support accompanied by the formation of interfacial structure (Ptδ+-Ov-Ce3+), which plays a crucial role in stabilizing Pt nanoclusters. A comprehensive investigation based on experimental studies and theoretical calculations substantiates that the interfacial sites serve as the intrinsic active center toward water-gas shift reaction (WGSR), featuring a moderate strength CO activation adsorption and largely decreased energy barrier of H2O dissociation, accounting for the prominent catalytic activity of Pt/CeO2(110) (a reaction rate of 15.76 molCO gPt-1 h-1 and a turnover frequency value of 2.19 s-1 at 250 °C). In addition, the Pt/CeO2(110) catalyst shows a prominent durability within a 120 h time-on-stream test, far outperforming the Pt/CeO2(100) one, which demonstrates the advantages of this embedding structure for improving catalyst stability.

11.
Mol Cancer ; 23(1): 73, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38581063

ABSTRACT

T cells are fundamental components in tumour immunity and cancer immunotherapies, which have made immense strides and revolutionized cancer treatment paradigm. However, recent studies delineate the predicament of T cell dysregulation in tumour microenvironment and the compromised efficacy of cancer immunotherapies. CRISPR screens enable unbiased interrogation of gene function in T cells and have revealed functional determinators, genetic regulatory networks, and intercellular interactions in T cell life cycle, thereby providing opportunities to revamp cancer immunotherapies. In this review, we briefly described the central roles of T cells in successful cancer immunotherapies, comprehensively summarised the studies of CRISPR screens in T cells, elaborated resultant master genes that control T cell activation, proliferation, fate determination, effector function, and exhaustion, and highlighted genes (BATF, PRDM1, and TOX) and signalling cascades (JAK-STAT and NF-κB pathways) that extensively engage in multiple branches of T cell responses. In conclusion, this review bridged the gap between discovering element genes to a specific process of T cell activities and apprehending these genes in the global T cell life cycle, deepened the understanding of T cell biology in tumour immunity, and outlined CRISPR screens resources that might facilitate the development and implementation of cancer immunotherapies in the clinic.


Subject(s)
Neoplasms , T-Lymphocytes , Humans , Clustered Regularly Interspaced Short Palindromic Repeats , Immunotherapy , Signal Transduction , Neoplasms/genetics , Neoplasms/therapy , Tumor Microenvironment/genetics
12.
BMC Med ; 22(1): 199, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755585

ABSTRACT

BACKGROUND: The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS). RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)]. CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.


Subject(s)
B7-H1 Antigen , Biomarkers, Tumor , Maintenance Chemotherapy , Ovarian Neoplasms , Phthalazines , Piperazines , Humans , Female , Phthalazines/therapeutic use , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Piperazines/therapeutic use , Biomarkers, Tumor/genetics , Middle Aged , Maintenance Chemotherapy/methods , Aged , Adult , Prospective Studies , Neoplasm Recurrence, Local/drug therapy , BRCA2 Protein/genetics , Antineoplastic Agents/therapeutic use , BRCA1 Protein/genetics , Homologous Recombination
13.
Eur J Nucl Med Mol Imaging ; 51(8): 2338-2352, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38411667

ABSTRACT

PURPOSE: Vascular endothelial growth factor receptor 3 (VEGFR-3) plays a critical role in tumor lymphangiogenesis and metastasis, holding promise as a promising therapeutic target for solid tumors. TMVP1 (LARGR) is a 5-amino acid peptide previously identified in our laboratory from bacterial peptide display system that specifically targets VEGFR-3. Radiolabeled TMVP1 can be used for non-invasive imaging of VEGFR-3 expressing tumors. Homodimeric peptides have better targeting ability than monomeric peptides, and it is worth exploring whether homodimers of TMVP1 ((TMVP1)2) can achieve better imaging effects. This study aimed to explore the peptide properties and tumor assessment value of [68Ga]Ga-labeled (TMVP1)2. METHODS: In this study, we developed a TMVP1 homodimer that was conjugated with 1,4,7-triazacyclononane-N, N', N″-triacetic acid (NOTA) via tetraethyleneglycol (PEG4) and triglyicine (Gly3) spacer, and labeled with 68Ga, to construct [68Ga]Ga-NOTA-(TMVP1)2. Binding of VEGFR-3 by TMVP1 and (TMVP1)2, respectively, was modeled by molecular docking. The affinity of [68Ga]Ga-NOTA-(TMVP1)2 for VEGFR-3 and its ability to bind to cells were evaluated. MicroPET imaging and biodistribution studies of [68Ga]Ga-NOTA-(TMVP1)2 were performed in subcutaneous C33A cervical cancer xenografts. Five healthy volunteers and eight patients with cervical cancer underwent whole-body PET/CT acquisition 30-45 min after intravenous injection of [68Ga]Ga-NOTA-(TMVP1)2. RESULTS: Both molecular docking and cellular experiments showed that homodimeric TMVP1 had a higher affinity for VEGFR-3 than monomeric TMVP1. [68Ga]Ga-NOTA-(TMVP1)2 was excreted mainly through the renal route and partly through the liver route. In mice bearing C33A xenografts, [68Ga]Ga-NOTA-(TMVP1)2 specifically localized in the tumor (2.32 ± 0.10% ID/g). Pretreatment of C33A xenograft mice with the unlabeled peptide NOTA-(TMVP1)2 reduced the enrichment of [68Ga]Ga-NOTA-(TMVP1)2 in tumors (0.58 ± 0.01% ID/g). [68Ga]Ga-NOTA-(TMVP1)2 proved to be safe in all healthy volunteers and recruited patients, with no side effects or allergies noted. In cervical cancer patients, a majority of the [18F]-FDG identified lesions (18/22, 81.8%) showed moderate to high signal intensity on [68Ga]Ga-NOTA-(TMVP1)2. SUVmax and SUVmean were 2.32 ± 0.77 and 1.61 ± 0.48, respectively. With normal muscle (gluteus maximus) as background, tumor-to-background ratios were 3.49 ± 1.32 and 3.95 ± 1.64 based on SUVmax and SUVmean, respectively. CONCLUSION: The favorable characterizations of [68Ga]Ga-NOTA-(TMVP1)2 such as convenient synthesis, high specific activity, and high tumor uptake enable the evaluation of VEGFR-3 in cervical cancer patients and warrant further clinical studies. TRIAL REGISTRATION: ChiCTR-DOD-17012458. Registered August 23, 2017 (retrospectively registered).


Subject(s)
Gallium Radioisotopes , Heterocyclic Compounds, 1-Ring , Uterine Cervical Neoplasms , Vascular Endothelial Growth Factor Receptor-3 , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/metabolism , Humans , Female , Animals , Mice , Heterocyclic Compounds, 1-Ring/chemistry , Vascular Endothelial Growth Factor Receptor-3/metabolism , Vascular Endothelial Growth Factor Receptor-3/chemistry , Gallium Radioisotopes/chemistry , Cell Line, Tumor , Heterocyclic Compounds/chemistry , Tissue Distribution , Peptides/chemistry , Peptides/pharmacokinetics , Positron Emission Tomography Computed Tomography/methods , Radiopharmaceuticals/pharmacokinetics , Radiopharmaceuticals/chemistry , Middle Aged , Protein Multimerization , Radioactive Tracers
14.
Langmuir ; 40(17): 9068-9081, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38628152

ABSTRACT

Shockwave-induced changes in nanobubbles cause cavitation erosion and membrane damage but can also be applied to biocarrier transport. Currently, research focuses on single nanobubbles; however, in reality, nanobubbles usually appear as a multibubble system. Therefore, this study proposes a method based on cutting and replicating to construct a multibubble model. This method can be widely applied to molecular dynamics (MD) models and enhance the customization capabilities of MD models. The dynamic behavior of a multinanobubble system with different numbers and arrangements of nanobubbles is investigated with the MD method under the influence of shock waves in a liquid argon system. The study also explores the range of influence between nanobubbles. The results show that in the case of two nanobubbles, when the distance between the bubbles is constant, the smaller the angle between the direction of the shock wave and the line connecting the bubbles, the greater is the influence between nanobubbles, and the moment of collapse of the nanobubbles farther away from the shock wave is slower. When three nanobubbles are arranged with a right offset, after the first bubble collapses, the effect on the other two bubbles is similar to the changes in bubbles when the angle of arrangement is 30° or 60°. Under a different arrangement, the change of shock wave velocity on the nanobubble size only affects its collapse time and contraction collapse rate. When the shock wave with a radian of about 2.87 or greater than 2.87 touches the bubbles, the collapse of the second nanobubble will not be affected.

15.
BJOG ; 131(3): 309-318, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37408516

ABSTRACT

OBJECTIVE: Human papillomavirus (HPV) integration is a crucial genetic step in cervical carcinogenesis. This study aimed to evaluate the performance of an HPV integration test for the triage of HPV-positive women. DESIGN: An observational cohort study. SETTING: A cervical cancer screening programme in China. POPULATION: 1393 HPV-positive women aged 25-65 years undergoing routine cervical cancer screening and HPV integration testing with 1-year follow-up. METHODS: The sensitivity, specificity, positive predictive value and negative predictive value between HPV integration and cytology were compared. MAIN OUTCOME MEASURES: Cervical intraepithelial neoplasia grade 3 or more severe (CIN3+). RESULTS: Among 1393 HPV-positive patients, 138 (9.9% [8.3-11.5%]) were HPV integration test positive compared with 537 who had abnormal cervical cytology (38.5% [36.0-41.1%]). Compared with cytology, HPV integration exhibited higher specificity (94.5% [93.3-95.8%] versus 63.8% [61.2-66.4%]) and equivalent sensitivity (70.5% [61.4-79.7%] versus 70.5% [61.4-79.7%]) for detection of CIN3+. HPV integration-negative women accounted for 90.1% (1255/1393) of the total population and had a low immediate CIN3+ risk (2.2%). At 1-year follow-up, the progression rate in the HPV integration-positive women was higher than in the HPV integration-negative women (12.0% versus 2.1%, odds ratio 5.6, 95% CI, 2.6-11.9). In 10 conservatively managed integration-negative CIN2 patients, all showed spontaneous regression and seven showed HPV clearance after 1-year follow-up. CONCLUSION: The HPV integration test may be a precise risk stratification tool for HPV-positive women and could avoid excessive use of invasive biopsies.


Subject(s)
Papillomavirus Infections , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Humans , Female , Pregnancy , Uterine Cervical Neoplasms/pathology , DNA, Viral , Papillomavirus Infections/complications , Papillomavirus Infections/diagnosis , Early Detection of Cancer , Uterine Cervical Dysplasia/diagnosis , Cohort Studies , Papillomaviridae/genetics , Vaginal Smears , Colposcopy
16.
Phys Chem Chem Phys ; 26(15): 11945-11957, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38573064

ABSTRACT

Low-velocity shock wave-induced contraction and expansion of nanobubbles can be applied to biocarriers and microfluidic systems. Although experiments have been conducted to study the application effects, the dynamic behavior characteristics of nanobubbles remain unexplored. In this work, we utilize molecular dynamics (MD) simulations to investigate the dynamic behavior characteristics of nanobubbles influenced by low-velocity shock waves in a liquid argon system. The DBSCAN (Density-Based Spatial Clustering of Applications with Noise) machine learning method is used to calculate the equivalent radius of nanobubbles. Two statistical methods are then utilized to predict the time series changes in the equivalent radius of nanobubbles without rebound shock waves. The piston velocity is analyzed using the bisection method to obtain the critical impact states of the nanobubble. The results show that at the low velocity shock wave (piston velocity of 0.1 km s-1), the shock wave pressure is small, the non-vacuum nanobubbles contract and expand in a circular shape, and the gas particles inside the bubble are not dispersed. In contrast, the vacuum nanobubbles collapse directly. As the shock wave rebounds upon impact, it triggers periodic contraction and expansion of the nanobubbles. The predictions indicate that the equivalent radius will vary within a small range according to the pre-predicted values in the absence of the rebound shock wave. Nanobubbles are present in four critical impact states: dispersed gaps, multiple smaller bubbles, two split bubbles, and a concave bubble.

17.
Environ Res ; 251(Pt 2): 118769, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38518918

ABSTRACT

This study aims to thoroughly investigate the impact mode of salinity carried by industrial wastewater on the anaerobic-anoxic-oxic (A2O) sludge in wastewater treatment plants (WWTPs). Through comprehensive investigation of the A2O stage activated sludge (AS) from 19 industrial WWTPs in the downstream area of the Yangtze River, China, A total of 38 samples of anaerobic sludge and oxic sludge were collected and analyzed. We found that salinity stress significantly inhibits the growth of the AS community, particularly evident in the anaerobic sludge community. Furthermore, the high-saline environment induces changes in the structure and functional patterns of the AS community, leading to intensive interactions and resource exchanges among microorganisms. Halophilic microorganisms may play a crucial role in this process, significantly impacting the overall community structure, especially in the oxic sludge community. Additionally, salinity stress not only suppresses the nitrogen transformation potential of the AS but also leads to the accumulation of nitrite, thereby increasing the emission potential of both NO and N2O, exacerbating the greenhouse effect of the A2O process in industrial WWTPs. The findings of this study provide necessary theoretical support for maintaining the long-term stable operation of the A2O sludge system in industrial WWTPs, reducing carbon footprint, and improving nitrogen removal efficiency.


Subject(s)
Nitrogen , Rivers , Salinity , Sewage , China , Sewage/microbiology , Rivers/microbiology , Rivers/chemistry , Nitrogen/metabolism , Nitrogen/analysis , Microbiota , Waste Disposal, Fluid/methods , Industrial Waste
18.
Environ Res ; 252(Pt 1): 118843, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38582429

ABSTRACT

Recently, the newly discovered anaerobic ammonium oxidation coupled with iron reduction (i.e., Feammox) has been proven to be a widespread nitrogen (N) loss pathway in ecosystems and has an essential contribution to gaseous N loss in paddy soil. However, the mechanism of iron-nitrogen coupling transformation and the role of iron-reducing bacteria (IRB) in Feammox were poorly understood. This study investigated the Feammox and iron reduction changes and microbial community evolution in a long-term anaerobic incubation by 15N isotope labeling combined with molecular biological techniques. The average rates of Feammox and iron reduction during the whole incubation were 0.25 ± 0.04 µg N g-1 d-1 and 40.58 ± 3.28 µg Fe g-1 d-1, respectively. High iron oxide content increased the Feammox rate, but decreased the proportion of Feammox-N2 in three Feammox pathways. RBG-13-54-9, Brevundimonas, and Pelomonas played a vital role in the evolution of microbial communities. The characteristics of asynchronous changes between Feammox and iron reduction were found through long-term incubation. IRB might not be the key species directly driving Feammox, and it is necessary to reevaluate the role of IRB in Feammox process.


Subject(s)
Iron , Oxidation-Reduction , Soil Microbiology , Soil , China , Iron/metabolism , Soil/chemistry , Bacteria/metabolism , Ammonium Compounds/analysis , Ammonium Compounds/metabolism
19.
Environ Res ; 252(Pt 2): 118833, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38599446

ABSTRACT

Thiocyanate (SCN-), a non-volatile inorganic pollutant, is commonly found in various types of industrial wastewater, which is resistant to hydrolysis and has the potential to be toxic to organisms. Premagnetized iron-copper-carbon ternary micro-electrolytic filler (pre-Fe/Cu/C) was prepared to degrade SCN-. Pre-Fe/Cu/C exhibited the most significant enhancement effect on SCN- removal when magnetized for 5 min with an intensity of 100 mT, and the SCN- removal rate was the highest at an initial pH of 3.0 and an aeration rate of 1.6 L/min. The electrochemical corrosion and electron transfer in the pre-Fe/Cu/C system were confirmed through SEM, XPS, FTIR, XRD, and electrochemical tests. This resulted in the formation of more corrosion products and multiple cycles of Fe2+/Fe3+ and Cu0/Cu+/Cu2+. Additionally, density functional theory (DFT) calculations and electron paramagnetic resonance (EPR) were utilized to illustrate the oxygen adsorption properties of the materials and the participation of reactive oxygen species (1O2, ·O2-, and ·OH) in SCN- removal. The degradation products of SCN- were identified as SO42-, HCO3-, NH4+, and N2. This study introduced the use of permanent magnets for the first time to enhance Fe/Cu/C ternary micro-electrolytic fillers, offering a cost-effective, versatile, and stable approach that effectively effectively enhanced the degradation of SCN-.


Subject(s)
Copper , Iron , Thiocyanates , Water Pollutants, Chemical , Thiocyanates/chemistry , Copper/chemistry , Iron/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/analysis , Carbon/chemistry , Corrosion
20.
Sensors (Basel) ; 24(11)2024 May 31.
Article in English | MEDLINE | ID: mdl-38894343

ABSTRACT

Circulating tumor cells are typically found in the peripheral blood of patients, offering a crucial pathway for the early diagnosis and prediction of cancer. Traditional methods for early cancer diagnosis are inefficient and inaccurate, making it difficult to isolate tumor cells from a large number of cells. In this paper, a new spiral microfluidic chip with asymmetric cross-section is proposed for rapid, high-throughput, label-free enrichment of CTCs in peripheral blood. A mold of the desired flow channel structure was prepared and inverted to make a trapezoidal cross-section using a micro-nanotechnology process of 3D printing. After a systematic study of how flow rate, channel width, and particle concentration affect the performance of the device, we utilized the device to simulate cell sorting of 6 µm, 15 µm, and 25 µm PS (Polystyrene) particles, and the separation efficiency and separation purity of 25 µm PS particles reached 98.3% and 96.4%. On this basis, we realize the enrichment of a large number of CTCs in diluted whole blood (5 mL). The results show that the separation efficiency of A549 was 88.9% and the separation purity was 96.4% at a high throughput of 1400 µL/min. In conclusion, we believe that the developed method is relevant for efficient recovery from whole blood and beneficial for future automated clinical analysis.


Subject(s)
Cell Separation , Lab-On-A-Chip Devices , Neoplastic Cells, Circulating , Humans , Cell Separation/methods , Cell Separation/instrumentation , Neoplastic Cells, Circulating/pathology , A549 Cells , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Printing, Three-Dimensional
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