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1.
IUCrdata ; 9(Pt 7): x240630, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39108935

ABSTRACT

In the title compound, [Co(C8H6N3O2)Cl(C2H5OH)] n , the CoII atoms adopt octa-hedral trans-CoN2O4 and tetra-hedral CoCl2O2 coordination geometries (site symmetries and m, respectively). The bridging µ3-O:O:N 2-(benzotriazol-1-yl)acetato ligands connect the octa-hedral cobalt nodes into (010) sheets and the CoCl2 fragments link the sheets into a tri-periodic network. The structure displays O-H⋯O hydrogen bonding and the ethanol mol-ecule is disordered over two orientations.

2.
Arch Toxicol ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38992170

ABSTRACT

Genetic variants can affect gene expression by altering the level of N6-methyladenosine (m6A) modifications. A better understanding of the association of these genetic variants with susceptibility to cervical cancer (CC) can promote advances in disease screening and treatment. Genome-wide identification of m6A-associated functional SNPs for CC was performed using the TCGA and JENGER databases, incorporating the data from RNA-seq and MeRIP-seq. The screened risk-associated SNP rs1059288 (A>G), which is located in the 3' UTR of TAPBP, was further validated in a case-control study involving 921 cases and 1077 controls. The results revealed a significant association between rs1059288 and the risk of CC (OR 1.48, 95% CI 1.13-1.92). Mechanistically, the presence of the risk G allele of rs1059288 was associated with increased m6A modification of TAPBP compared with the A allele. This modification was facilitated by the m6A methyltransferase METTL14 and the reading protein YTHDF2. Immunohistochemical staining of tissue microarrays containing 61 CC and 45 normal tissues showed an overexpression of TAPBP in CC. Furthermore, the upregulation of TAPBP promoted the growth and migration of CC cells as well as tumor-forming ability, inhibited apoptosis, and conferred increased resistance to commonly used chemotherapeutic drugs such as bleomycin, cisplatin, and doxorubicin. Knockdown of TAPBP inhibited the JAK/STAT/MICB signaling pathway in CC cells and upregulated certain immune genes including ISG15, IRF3, PTPN6, and HLA-A. These findings offer insights into the involvement of genetic variations in TAPBP in the development and progression of CC.

3.
Int J Colorectal Dis ; 39(1): 108, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008124

ABSTRACT

BACKGROUND AND AIMS: Video-assisted anal fistula treatment (VAAFT) is an innovative surgical approach enabling the direct visualization of the fistula tract structure. This study aims to assess the efficacy of VAAFT in comparison with that of traditional surgical methods and explore potential risk factors contributing to fistula recurrence to provide new recommendations for surgical selection. MATERIALS AND METHODS: Information was collected from 100 patients with complex anal fistula (CAF) in our hospital who underwent surgical treatment from January 2021 to January 2023. We compared the baseline information and surgical outcomes of two groups, analyzed the risk factors for fistula recurrence by using logistic regression analysis, and conducted further exploration by using the body mass index. RESULTS: Equal numbers of patients underwent VAAFT and traditional surgeries, and no significant differences in baseline information were observed. Patients who received VAAFT experienced less intraoperative bleeding (15.5 (14.0-20.0) vs. 32.0 (25.0-36.0)), shorter hospital stays (2.0 (2.0-2.5) vs. 3.0 (3.0-3.5)), reduced postoperative pain and wound discharge, but longer operative times (43.3 ± 6.9 vs. 35.0 (31.5-40.0)) compared with patients who underwent traditional surgeries. No significant differences in recurrence rates were found three and six months after operation (the p-values were 0.790 and 0.806, respectively). However, the Wexner scores of the VAAFT group were significantly low in the first follow-up (0 (0-1.0) vs. 2.0 (1.0-2.0)). Postoperative recurrence of fistulas may be associated with obesity (p-value = 0.040), especially in patients undergoing traditional surgeries (p-value = 0.036). CONCLUSION: VAAFT offers advantages, such as less pain, less trauma, and faster recovery, compared with traditional surgical treatment. Obese patients with CAF are prone to recurrence, and we recommend that they undergo VAAFT treatment rather than traditional surgeries.


Subject(s)
Obesity , Rectal Fistula , Recurrence , Video-Assisted Surgery , Humans , Rectal Fistula/surgery , Rectal Fistula/etiology , Obesity/complications , Obesity/surgery , Female , Male , Treatment Outcome , Middle Aged , Adult , Risk Factors , Body Mass Index , Operative Time , Length of Stay
4.
Heliyon ; 10(13): e33597, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39040415

ABSTRACT

Aims: To identify and analyze genes closely related to the progression of nonalcoholic steatohepatitis (NASH) by employing a combination of single-cell RNA sequencing and machine-learning algorithms. Main methods: Single-cell RNA sequencing (scRNA-seq) analysis was performed to find the cell population with the most significant differences between the Chow and NASH groups. This approach was used to validate the developmental trajectory of this cell population and investigate changes in cellular communication and important signaling pathways among these cells. Subsequently, high dimensional Weighted Gene Co-expression Network Analysis (hdWGCNA) was used to find the key modules in NASH. Machine learning analyses were performed to further identify core genes. Deep learning techniques were applied to elucidate the correlation between core genes and immune cells. The accuracy of this correlation was further confirmed using deep learning techniques, specifically Convolutional Neural Networks. Key findings: By comparing scRNA-seq data between the Chow and NASH groups, we have observed a notable distinction existing in the Kupffer cell population. Signaling interactions between hepatic macrophages and other cells were significantly heightened in the NASH group. Through subsequent analysis of macrophage subtypes and key modules, we identified 150 genes tightly associated with NASH. Finally, we highlighted the 16 most significant core genes using multiple iterations of machine learning. Furthermore, we pointed out the close relationship between core genes and immune cells. Significances: Using scRNA-seq analysis and machine learning, we can distinguish NASH-related genes from large genetic datasets, providing theoretical support in finding potential targets for the development of novel therapies.

5.
Front Aging Neurosci ; 16: 1433094, 2024.
Article in English | MEDLINE | ID: mdl-39026989

ABSTRACT

Introduction: Neuroinflammation serves as a critical local defense mechanism against secondary brain injury following intracerebral hemorrhage (ICH), and astrocytes play a prominent role in this process. In this study, we investigated astrocytic changes during the inflammatory state after ICH to identify new targets for improving the inflammatory response. Methods: We stimulated mouse astrocytes with lipopolysaccharide (LPS) in vitro and analyzed their transcriptomes via ribonucleic acid sequencing. We created an ICH model in living organisms by injecting autologous blood. Results: RNA sequencing revealed that 2,717 genes were differentially expressed in the LPS group compared to those in the saline group, with notable enrichment of the autophagic pathway. By intersecting the 2,717 differentially expressed genes (DEGs) with autophagy-related genes, we identified 36 autophagy-related DEGs and seven hub genes. Previous studies and quantitative reverse transcription-polymerase chain reaction results confirmed the increased expression of phosphatidylinositol 3-kinase catalytic subunit type 3 (Pik3c3), AKT serine/threonine kinase 1 (Akt1), and unc-51 like autophagy activating kinase 2 (Ulk2) in astrocytes after ICH. Transcription factors and target miRNAs were identified for the final three DEGs, and 3-methyladenine and leupeptin were identified as potential therapeutic agents for ICH. Conclusion: Our findings suggest that astrocyte autophagy plays a critical role in ICH complexity, and that Pik3c3, Akt1, and Ulk2 may be potential therapeutic targets.

6.
Small ; : e2403993, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-39031746

ABSTRACT

Polyvinylidene fluoride (PVDF) has unique electrochemical oxidation resistance and is the only binder for high-voltage cathode materials in the battery industry for a long time. However, PVDF still has some drawbacks, such as environmental limitations on fluorine, strict requirements for environmental humidity, weak adhesion, and poor lithium ion conductivity. Herein, the long-standing issues associated with high-voltage lithium cobalt oxide (LiCoO2; LCO) are successfully addressed by incorporating phenolphthalein polyetherketone (PEK-C) and phenolphthalein polyethersulfone (PES-C) as binder materials. These binders have unexpected electrochemical oxidation resistance and robustness adhesion, ensure uniform coverage on the surface of LCO, and establish an effective and fast ion-conductive CEI/binder composite layer. By leveraging these favorable characteristics, electrodes based on polyarylether binders demonstrate significantly better cycling and rate performance than their counterparts using traditional PVDF binders. The fast ion-conductive CEI/binder composite layer effectively mitigates adverse reactions at the cathode-electrolyte interface. As anticipated, batteries utilizing phenolphthalein polyarylether binders exhibit capacity retention rates of 88.92% and 80.4% after 200 and 500 cycles at 4.5 and 4.6 V, respectively. The application of binders, such as polyarylether binders, offers a straightforward and inspiring approach for designing high-energy-density battery materials.

8.
BMC Musculoskelet Disord ; 25(1): 600, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39080680

ABSTRACT

PURPOSE: We aimed to develop and evaluate a new diagnostic method, the 'chicken-wing muscle up test', to improve the accuracy of diagnosis of glenolabral articular disruption (GLAD) lesions compared to currently used clinical tests for injuries to the labrum. METHODS: Preoperative evaluations were conducted on 85 patients undergoing arthroscopic surgery at a single center between July 2021 to July 2022. The diagnostic performance of the preoperative clinical examinations (chicken-wing muscle up test, O'Brien test, crank test, and O'Driscoll test) were validated against the findings of arthroscopic examinations. RESULTS: 12 of the 85 patients in this study had arthroscopically confirmed GLAD lesions. The chicken-wing muscle up test demonstrated significantly higher sensitivity (83.33%) for GLAD lesions than the O'Brien test (33.33%), but not the crank test (50.00%) or O'Driscoll test (25.00%), and significantly higher specificity (95.89%) than the O'Brien test (75.34%), crank test (82.19%), and O'Driscoll test (71.23%). The chicken-wing muscle up test had the largest area under the receiver operating characteristic curve (AUC = 0.896, P < 0.001; O'Driscoll test AUC = 0.543, P > 0.05; crank test AUC = 0.661, P > 0.05; O'Brien test AUC = 0.481, P > 0.05), indicating significantly better diagnostic efficacy for GLAD lesions than the other three tests. CONCLUSIONS: The chicken-wing muscle up test is a reliable diagnostic method that improves the accuracy of diagnosis of GLAD lesions.


Subject(s)
Arthroscopy , Humans , Female , Male , Adult , Arthroscopy/methods , Middle Aged , Young Adult , Muscle, Skeletal , Adolescent , Sensitivity and Specificity , Retrospective Studies , Physical Examination/methods
9.
Sci Rep ; 14(1): 15954, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987301

ABSTRACT

Gross ecosystem product (GEP) is an aggregate measure of the monetary value of final ecosystem services, or the direct benefits that people derive from nature. GEP can provide decision makers with clear and competing evidence of the monetary value of ecosystem services. However, the relationship between GEP and urbanization has not been clarified which is not conducive to the decision-making role of GEP in the process of urban sustainable development. This work focused on the 'Beijing-Tianjin-Hebei' (BTH) urban agglomeration as a case study of the dynamics of ecological production amidst rapid economic and urban development, and coupled a spatial-temporal analysis of regional ecological change based on GIS (Geographic Information System) with economic valuation methods using official statistics and survey data. Results showed that from 2000 to 2020, the GEP increased from 1.55 trillion to 2.36 trillion, the value of provisioning services and cultural services increased from 0.51 to 0.71 trillion to 0.10-0.65 trillion. The value of regulation services showed an upward and downward trend (0.94-1.03-0.98) due to the rapid economic development in the Beijing-Tianjin-Hebei region. There were obvious spatial differences in the distribution of the GEP, in which Beijing, Tianjin, Tangshan, Cangzhou GEP accounted for 15%, 14%, 16% and 11%, respectively. During 2000-2020, there is a significant correlation between urbanization index (UI) and GEP in BTH, but the correlation between GEP and UI shows a trend of first increasing and then decreasing. The correlation between UI and EPS and ERS gradually decreases, and the impact of UI on ETS shows a significant positive correlation. In the future, it can be foreseen that urbanization will suppress the increase of GEP.

10.
Am J Physiol Cell Physiol ; 327(2): C329-C340, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38881420

ABSTRACT

Family with sequence similarity 135 member B (FAM135B) is a novel driver gene in esophageal squamous cell carcinoma (ESCC). However, little is known regarding its biological functions and mechanisms in ESCC. Here, we identified that the high expression of FAM135B was associated with lymph node metastasis and infiltrating development of ESCC. Elevated FAM135B expression promoted ESCC migration and invasion in vitro and lung metastasis in vivo. Furthermore, epithelial-mesenchymal transition (EMT)-related pathways were enriched in ESCC samples with high levels of FAM135B and FAM135B positively regulated EMT markers. Mechanistically, we observed that FAM135B interacted with the intermediate domain of TRAF2 and NCK-interacting kinase (TNIK), activating the Wnt/ß-catenin signaling pathway. The facilitation of TNIK on ESCC migration and invasion was reversed by FAM135B siRNA. In addition, the N6-methyladenosine (m6A) modification positively regulated FAM135B expression, with methyltransferase like 3 (METTL3) acting as its substantial m6A writer. The pro-EMT effects of METTL3 overexpression were reversed by silencing FAM135B. Collectively, these findings illustrate the critical role of ABCDE in ESCC progression and provide new insights into the upstream and downstream mechanisms of FAM135B.NEW & NOTEWORTHY This study reveals for the first time that the novel cancer-related gene, FAM135B, promotes ESCC metastasis both in vitro and in vivo. Besides, we substantiate FAM135B's action on the ß-catenin pathway through interacting with TNIK, thereby elucidating the promotional effect of FAM135B on ESCC EMT. Furthermore, we provide initial evidence demonstrating that METTL3-mediated m6A modification upregulates the expression of FAM135B in ESCC cells.


Subject(s)
Cell Movement , Epithelial-Mesenchymal Transition , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Gene Expression Regulation, Neoplastic , Methyltransferases , Up-Regulation , Wnt Signaling Pathway , Humans , Wnt Signaling Pathway/genetics , Epithelial-Mesenchymal Transition/genetics , Methyltransferases/genetics , Methyltransferases/metabolism , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/metabolism , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Esophageal Neoplasms/metabolism , Cell Line, Tumor , Animals , Male , Female , Mice, Nude , Mice , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , beta Catenin/metabolism , beta Catenin/genetics , Neoplasm Invasiveness , Mice, Inbred BALB C , Lymphatic Metastasis , Middle Aged , Adenosine/analogs & derivatives , Adenosine/metabolism , Adenosine/genetics
11.
ACS Appl Mater Interfaces ; 16(27): 34902-34912, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38904546

ABSTRACT

The separator is a crucial component in lithium batteries, as it physically separates the cathode and the anode while allowing ion transfer through the internal channel. The pore structure of the separator significantly influences the performance of lithium batteries, particularly lithium metal batteries. In this study, we investigate the use of a Janus separator composed of poly(ethylene terephthalate) (PET)-polytetrafluoroethylene (PTFE) fibers in lithium metal batteries. This paper presents a comprehensive analysis of the impact of this asymmetric material on the cycling performance of the battery alongside an investigation into the influence of two different substrates on lithium-ion deposition behavior. The research findings indicate that when the rigid PET side faces the lithium metal anode and the soft PTFE side faces the cathode, it significantly extends the cycling lifespan of lithium metal batteries, with an impressive 82.6% capacity retention over 2000 cycles. Furthermore, this study demonstrates the versatility of this separator type in lithium metal batteries by assembling the lithium metal electrode with high cathode-loading capacities (4 mA h/cm2). In conclusion, the results suggest that the design of asymmetric separators can serve as an effective engineering strategy with substantial potential for enhancing the lifespan of lithium metal batteries.

13.
Front Biosci (Landmark Ed) ; 29(6): 206, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38940028

ABSTRACT

Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. Light plays an important role in the regulation of circadian rhythm in human body. When light from the outside enters the eyes, cones, rods, and specialized retinal ganglion cells receive the light signal and transmit it to the suprachiasmatic nucleus of the hypothalamus. The central rhythm oscillator of the suprachiasmatic nucleus regulates the rhythm oscillator of tissues all over the body. Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. As the largest organ in the human body, skin plays an important role in the peripheral circadian rhythm regulation system. Like photoreceptor cells in the retina, melanocytes express opsins. Studies show that melanocytes in the skin are also sensitive to light, allowing the skin to "see" light even without the eyes. Upon receiving light signals, melanocytes in the skin release hormones that maintain homeostasis. This process is called "photoneuroendocrinology", which supports the health effects of light exposure. However, inappropriate light exposure, such as prolonged work in dark environments or exposure to artificial light at night, can disrupt circadian rhythms. Such disruptions are linked to a variety of health issues, emphasizing the need for proper light management in daily life. Conversely, harnessing light's beneficial effects through phototherapy is gaining attention as an adjunctive treatment modality. Despite these advancements, the field of circadian rhythm research still faces several unresolved issues and emerging challenges. One of the most exciting prospects is the use of the skin's photosensitivity to treat diseases. This approach could revolutionize how we think about and manage various health conditions, leveraging the skin's unique ability to respond to light for therapeutic purposes. As research continues to unravel the complexities of circadian rhythms and their impact on health, the potential for innovative treatments and improved wellbeing is immense.


Subject(s)
Circadian Rhythm , Humans , Circadian Rhythm/physiology , Animals , Light , Signal Transduction
14.
Sci Rep ; 14(1): 13831, 2024 06 15.
Article in English | MEDLINE | ID: mdl-38879647

ABSTRACT

Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells (ECs) that play an important role in liver development and regeneration. Additionally, it is involved in various pathological processes, including steatosis, inflammation, fibrosis and hepatocellular carcinoma. However, the rapid dedifferentiation of LSECs after culture greatly limits their use in vitro modeling for biomedical applications. In this study, we developed a highly efficient protocol to induce LSEC-like cells from human induced pluripotent stem cells (hiPSCs) in only 8 days. Using single-cell transcriptomic analysis, we identified several novel LSEC-specific markers, such as EPAS1, LIFR, and NID1, as well as several previously revealed markers, such as CLEC4M, CLEC1B, CRHBP and FCN3. These LSEC markers are specifically expressed in our LSEC-like cells. Furthermore, hiPSC-derived cells expressed LSEC-specific proteins and exhibited LSEC-related functions, such as the uptake of acetylated low density lipoprotein (ac-LDL) and immune complex endocytosis. Overall, this study confirmed that our novel protocol allowed hiPSCs to rapidly acquire an LSEC-like phenotype and function in vitro. The ability to generate LSECs efficiently and rapidly may help to more precisely mimic liver development and disease progression in a liver-specific multicellular microenvironment, offering new insights into the development of novel therapeutic strategies.


Subject(s)
Cell Differentiation , Endothelial Cells , Induced Pluripotent Stem Cells , Liver , Humans , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Endothelial Cells/metabolism , Endothelial Cells/cytology , Liver/metabolism , Liver/cytology , Single-Cell Analysis/methods , Cells, Cultured , Biomarkers/metabolism , Lipoproteins, LDL/metabolism , Gene Expression Profiling
15.
Harmful Algae ; 134: 102623, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38705613

ABSTRACT

Microcystins release from bloom-forming cyanobacteria is considered a way to gain competitive advantage in Microcystis populations, which threaten water resources security and aquatic ecological balance. However, the effects of microcystins on microalgae are still largely unclear. Through simulated culture experiments and the use of UHPLC-MS-based metabolomics, the effects of two microcystin-LR (MC-LR) concentrations (400 and 1,600 µg/L) on the growth and antioxidant properties of three algae species, the toxic Microcystis aeruginosa, a non-toxic Microcystis sp., and Chlorella vulgaris, were studied. The MC-LR caused damage to the photosynthetic system and activated the protective mechanism of the photosynthetic system by decreasing the chlorophyll-a and carotenoid concentrations. Microcystins triggered oxidative stress in C. vulgaris, which was the most sensitive algae species studied, and secreted more glycolipids into the extracellular compartment, thereby destroying its cell structure. However, C. vulgaris eliminated reactive oxygen species (ROS) by secreting terpenoids, thereby resisting oxidative stress. In addition, two metabolic pathways, the vitamin B6 and the sphingolipid pathways, of C. vulgaris were significantly disturbed by microcystins, contributing to cell membrane and mitochondrial damage. Thus, both the low (400 µg/L) and the high (1,600 µg/L) MC-LR concentration inhibited algae growth within 3 to 7 days, and the inhibition rates increased with the increase in the MC-LR concentration. The above results indicate that the toxin-producing Microcystis species have a stronger toxin tolerance under longer-term toxin exposure in natural water environments. Thus, microcystins participates in interspecific interaction and phytoplankton population regulation and creates suitable conditions for the toxin-producing M. aeruginosa to become the dominant species in algae blooms.


Subject(s)
Antioxidants , Marine Toxins , Microcystins , Microcystis , Photosynthesis , Microcystins/metabolism , Photosynthesis/drug effects , Antioxidants/metabolism , Microcystis/drug effects , Microcystis/growth & development , Microcystis/metabolism , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Chlorella vulgaris/drug effects , Chlorella vulgaris/growth & development , Chlorella vulgaris/metabolism , Chlorophyll A/metabolism
16.
Adv Mater ; 36(30): e2403929, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38744294

ABSTRACT

2D polarization materials have emerged as promising candidates for meeting the demands of device miniaturization, attributed to their unique electronic configurations and transport characteristics. Although the existing inherent and sliding mechanisms are increasingly investigated in recent years, strategies for inducing 2D polarization with innovative mechanisms remain rare. This study introduces a novel 2D Janus state by modulating the puckered structure. Combining scanning probe microscopy, transmission electron microscopy, and density functional theory calculations, this work realizes force-triggered out-of-plane and in-plane dipoles with distorted smaller warping in GeSe. The Janus state is preserved after removing the external mechanical perturbation, which could be switched by modulating the sliding direction. This work offers a versatile method to break the space inversion symmetry in a 2D system to trigger polarization in the atomic scale, which may open an innovative insight into configuring novel 2D polarization materials.

17.
PLoS Med ; 21(5): e1004389, 2024 May.
Article in English | MEDLINE | ID: mdl-38728364

ABSTRACT

BACKGROUND: It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. METHODS AND FINDINGS: This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus ≥5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade ≥ 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade ≥ 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. CONCLUSIONS: The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03493048.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Camptothecin , Cetuximab , Colorectal Neoplasms , Fluorouracil , Leucovorin , Liver Neoplasms , Organoplatinum Compounds , Proto-Oncogene Proteins B-raf , Humans , Cetuximab/administration & dosage , Cetuximab/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Male , Middle Aged , Liver Neoplasms/secondary , Liver Neoplasms/drug therapy , Female , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Leucovorin/therapeutic use , Leucovorin/administration & dosage , Fluorouracil/therapeutic use , Fluorouracil/administration & dosage , Organoplatinum Compounds/therapeutic use , Organoplatinum Compounds/administration & dosage , Proto-Oncogene Proteins B-raf/genetics , Aged , Adult , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Camptothecin/administration & dosage , Treatment Outcome , ras Proteins/genetics
18.
J Pharm Biomed Anal ; 246: 116213, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38754155

ABSTRACT

Triterpenoid saponins, a major bioactive component of liquorice, possess high hydrophilicity and often co-occur with other impurities of similar polarity. Additionally, subtle structural differences of some triterpenoid saponins bring challenges to comprehensive characterisation. In this study, triterpenoid saponins of three Glycyrrhiza species were systematically analysed using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF-MS) coupled with mass defect filtering (MDF). Firstly, comprehensive date acquisition was achieved using RRLC-Q-TOF-MS. Secondly, a polygonal MDF method was established by summarizing known and speculated substituents and modifications based on the core structure to rapidly screen potential triterpenoid saponins. Thirdly, based on the fragmentation patterns of reference compounds, an identification strategy for characterisation of triterpenoid saponins was proposed. The strategy divided triterpenoid saponins into three distinct classes. By this strategy, 98 triterpenoid saponins including 10 potential new ones were tentatively characterised. Finally, triterpenoid saponins of three Glycyrrhiza species were further analysed using principle component analysis (PCA) and orthogonality partial least squares discriminant analysis (OPLS-DA). Among these, 18 compounds with variable importance in projections (VIP) > 1.0 and P values < 0.05 were selected to distinguish three Glycyrrhiza species. Overall, our study provided a reference for quality control and rational use of the three species.


Subject(s)
Glycyrrhiza , Saponins , Triterpenes , Saponins/chemistry , Saponins/analysis , Glycyrrhiza/chemistry , Triterpenes/chemistry , Triterpenes/analysis , Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods , Chromatography, Liquid/methods , Plant Extracts/chemistry
19.
Food Chem ; 453: 139633, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-38781896

ABSTRACT

Smilax glabra Roxb. (SGR) is known for its high nutritional and therapeutic value. However, the frequent appearance of counterfeit products causes confusion and inconsistent quality among SGR varieties. Herein, this study collected the proportion of SGR adulteration and used high-performance liquid chromatography (HPLC) to measure the astilbin content of SGR. Then Fourier-transform near-infrared (FT-NIR) technology, combined with multivariate intelligent algorithms, was used to establish partial least squares regression quantitative models for detecting SGR adulteration and measuring astilbin content, respectively. The method conducted a quantitative analysis of dual indicators through single-spectrum data acquisition (QADS) to comprehensively evaluate the authenticity and superiority of SGR. The coefficients of determination (R2) for both the calibration and prediction sets exceeded 0.96, which successfully leverages FT-NIR combined with multivariate intelligent algorithms to considerably enhance the accuracy and reliability of quantitative models. Overall, this research holds substantial value in the comprehensive quality evaluation in functional health foods.


Subject(s)
Algorithms , Smilax , Spectroscopy, Near-Infrared , Smilax/chemistry , Spectroscopy, Near-Infrared/methods , Chromatography, High Pressure Liquid , Quality Control , Spectroscopy, Fourier Transform Infrared , Plant Extracts/chemistry , Plant Extracts/analysis , Least-Squares Analysis
20.
Nat Mater ; 23(7): 928-936, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38777873

ABSTRACT

Controlling topological phases of light allows the observation of abundant topological phenomena and the development of robust photonic devices. The prospect of more sophisticated control with topological photonic devices for practical implementations requires high-level programmability. Here we demonstrate a fully programmable topological photonic chip with large-scale integration of silicon photonic nanocircuits and microresonators. Photonic artificial atoms and their interactions in our compound system can be individually addressed and controlled, allowing the arbitrary adjustment of structural parameters and geometrical configurations for the observation of dynamic topological phase transitions and diverse photonic topological insulators. Individual programming of artificial atoms on the generic chip enables the comprehensive statistical characterization of topological robustness against relatively weak disorders, and counterintuitive topological Anderson phase transitions induced by strong disorders. This generic topological photonic chip can be rapidly reprogrammed to implement multifunctionalities, providing a flexible and versatile platform for applications across fundamental science and topological technologies.

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