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1.
J Environ Sci (China) ; 148: 364-374, 2025 Feb.
Article in English | MEDLINE | ID: mdl-39095171

ABSTRACT

Increasing nitrogen and phosphorus discharge and decreasing sediment input have made silicon (Si) a limiting element for diatoms in estuaries. Disturbances in nutrient structure and salinity fluctuation can greatly affect metal uptake by estuarine diatoms. However, the combined effects of Si and salinity on metal accumulation in these diatoms have not been evaluated. In this study, we aimed to investigate how salinity and Si availability combine to influence the adsorption of metals by a widely distributed diatom Phaeodactylum tricornutum. Our data indicate that replete Si and low salinity in seawater can enhance cadmium and copper adsorption onto the diatom surface. At the single-cell level, surface potential was a dominant factor determining metal adsorption, while surface roughness also contributed to the higher metal loading capacity at lower salinities. Using a combination of non-invasive micro-test technology, atomic force microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy, we demonstrate that the diversity and abundance of the functional groups embedded in diatom cell walls vary with salinity and Si supply. This results in a change in the cell surface potential and transient metal influx. Our study provides novel mechanisms to explain the highly variable metal adsorption capacity of a model estuarine diatom.


Subject(s)
Diatoms , Salinity , Silicon , Water Pollutants, Chemical , Adsorption , Silicon/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/analysis , Estuaries , Seawater/chemistry , Metals/chemistry
2.
Cancer Commun (Lond) ; 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39221992

ABSTRACT

BACKGROUND: In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high-level clinical evidence. This study aimed to compare the safety and long-term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. METHODS: A prospective, single-center, open-label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event-free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. RESULTS: Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1-3M0 to T2-3N0-3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1-year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1-year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien-Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups (12.5% versus 12.4%). CONCLUSIONS: The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

3.
Adv Sci (Weinh) ; : e2407578, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39225331

ABSTRACT

Doping narrow-gap semiconductors is a well-established approach for designing efficient thermoelectric materials. Semiconducting half-Heusler (HH) and full-Heusler (FH) compounds have garnered significant interest within the thermoelectric field, yet the number of exceptional candidates remains relatively small. It is recently shown that the vacancy-filling approach is a viable strategy for expanding the Heusler family. Here, a range of near-semiconducting Heuslers, TiFexCuySb, creating a composition continuum that adheres to the Slater-Pauling electron counting rule are theoretically designed and experimentally synthesized. The stochastic and incomplete occupation of vacancy sites within these materials imparts continuously changing electrical conductivities, ranging from a good semiconductor with low carrier concentration in the endpoint TiFe0.67Cu0.33Sb to a heavily doped p-type semiconductor with a stoichiometry of TiFe1.00Cu0.20Sb. The optimal thermoelectric performance is experimentally observed in the intermediate compound TiFe0.80Cu0.28Sb, achieving a peak figure of merit of 0.87 at 923 K. These findings demonstrate that vacancy-filling Heusler compounds offer substantial opportunities for developing advanced thermoelectric materials.

4.
Clin Sports Med ; 43(4): 661-682, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39232573

ABSTRACT

The indications for bone block augmentation of the glenoid following recurrent anterior shoulder instability are expanding. Arthroscopic anatomic glenoid reconstruction (AAGR) is an evolving technique with similar clinical results to the Latarjet procedure and other open bone block procedures. Multiple types of bone grafts and fixation techniques have been described, with varying results on bony integration, resorption, articular congruity, and recurrence rates. This review focuses on biomechanics, patient workup, indications, current evidence, and the authors' preferred surgical technique for AAGR.


Subject(s)
Arthroscopy , Bone Transplantation , Joint Instability , Humans , Arthroscopy/methods , Bone Transplantation/methods , Joint Instability/surgery , Shoulder Joint/surgery , Biomechanical Phenomena
6.
Eur J Med Chem ; 279: 116803, 2024 Sep 02.
Article in English | MEDLINE | ID: mdl-39255641

ABSTRACT

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) regulates programmed cell death and inflammation, contributing to a wide range of human pathologies, including inflammatory disorders, neurodegenerative conditions, and cancer. Despite this, no RIPK1 positron emission tomography (PET) ligand with significant in vivo specificity has been reported to date. In this work, we designed and synthesized a new family of dihydropyrazole-cored ligands suitable for 18F-labeling at the late stage. Among these, WL8 showed a strong binding affinity to RIPK1 (EC50 = 19.9 nM, Kd = 25 nM) and was successfully labeled with 18F in the 6-position of pyridine ring, yielding a high radiochemistry yield of 27.9 % (decay-corrected) and a high molar activity of 18.8-31.2 GBq/µmol. In in vitro autoradiography, [18F]WL8 showed some specific binding in the brain sections of rats and lipopolysaccharide (LPS) model mice. Preliminary PET studies in rat brains revealed that [18F]WL8 could efficiently penetrate the blood-brain barrier and was rapidly washed out. As anticipated, [18F]WL8 exhibited a high initial uptake (brain2min = 4.80 % ID/g) in mouse brains, followed by a rapid washout (brain60min = 0.14 % ID/g), although no clear specific binding to RIPK1 was observed. Moderate in vivo stability was noted for [18F]WL8 in mouse brains with 35.2 % of the parent fraction remaining after 30 min post-administration. Altogether, our work broadens the landscape and offers a new chemotype for RIPK1 PET ligand development.

7.
Article in English | MEDLINE | ID: mdl-39259226

ABSTRACT

PURPOSE: Multiple myeloma (MM) is characterized by the uncontrolled proliferation of monoclonal plasma cells (PC) in the bone marrow (BM). B-cell maturation antigen (BCMA) is predominantly expressed in malignant plasma cells, and associated with the proliferation, survival, and progression of various myeloma cells. Given these important roles, BCMA emerges as an ideal target antigen for MM therapy. However, effective stratification of patients who may benefit from targeted BCMA therapy and real-time monitoring the therapeutic efficacy poses significant clinical challenge. This study aims to develop a BCMA targeted diagnostic modality, and preliminarily explore its potential value in the radio-immunotherapy of MM. EXPERIMENTAL DESIGN: Using zirconium-89 (89Zr, t1/2 = 78.4 h) for labeling the BCMA-specific antibody, the BCMA-targeting PET tracer [89Zr]Zr-DFO-BCMAh230430 was prepared. The EC50 values of BCMAh230430 and DFO-BCMAh230430 were determined by ELISA assay. BCMA expression was assessed in four different tumor cell lines (MM.1S, RPMI 8226, BxPC-3, and KYSE520) through Western blot and flow cytometry. In vitro binding affinity was determined by cell uptake studies of [89Zr]Zr-DFO-BCMAh230430 in these tumor cell lines. For in vivo evaluation, PET imaging and ex vivo biodistribution studies were conducted in tumor-bearing mice to evaluate imaging performance and systemic distribution of [89Zr]Zr-DFO-BCMAh230430. Immunochemistry analysis was performed to detect BCMA expression in tumor tissues, confirming the specificity of our probe. Furthermore, we explored the anti-tumor efficacy of Lutetium-177 labeled BCMA antibody, [177Lu]Lu-DTPA-BCMAh230430, in tumor bearing-mice to validate its radioimmunotherapy potential. RESULTS: The radiolabeling of [89Zr]Zr-DFO-BCMAh230430 and [177Lu]Lu-DTPA-BCMAh230430 showed satisfactory radiocharacteristics, with a radiochemical purity exceeding 99%. ELISA assay results revealed closely aligned EC50 values for BCMAh230430 and DFO-BCMAh230430, which are 57 pM and 67 pM, respectively. Western blot and flow cytometry analyses confirmed the highest BCMA expression level. Cell uptake data indicated that MM.1S cells had a total cellular uptake (the sum of internalization and surface binding) of 38.3% ± 1.53% for [89Zr]Zr-DFO-BCMAh230430 at 12 h. PET imaging of [89Zr]Zr-DFO-BCMAh230430 displayed radioactive uptake of 7.71 ± 0.67%ID/g in MM.1S tumors and 4.13 ± 1.21%ID/g in KYSE520 tumors at 168 h post-injection (n = 4) (P < 0.05), consistent with ex vivo biodistribution studies. Immunohistochemical analysis of tumor tissues confirmed higher BCMA expression in MM.1S tumors xenograft compared to KYSE520 tumors. Notably, [177Lu]Lu-DTPA-BCMAh230430 showed some anti-tumor efficacy, evidenced by slowed tumor growth. Furthermore, no significant difference in body weight was observed in MM.1S tumor-bearing mice over 14 days of administration with or without [177Lu]Lu-DTPA-BCMAh230430. CONCLUSIONS: Our study has successfully validated the essential role of [89Zr]Zr-DFO-BCMAh230430 in non-invasively monitoring BCMA status in MM tumors, showing favorable tumor uptake and specific binding affinity to MM tumors. Furthermore, our research revealed, as a proof-of-concept, the effectiveness of [177Lu]Lu-DTPA-BCMAh230430 in radioimmunotherapy for MM tumors. In conclusion, we present a novel BCMA antibody-based radiotheranostic modality that holds promise for achieving efficient and precise MM diagnostic and therapy.

9.
Adv Sci (Weinh) ; : e2406793, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39246254

ABSTRACT

Across diverse domains of science and technology, electromagnetic (EM) inversion problems benefit from the ability to account for multimodal prior information to regularize their inherent ill-posedness. Indeed, besides priors that are formulated mathematically or learned from quantitative data, valuable prior information may be available in the form of text or images. Besides handling semantic multimodality, it is furthermore important to minimize the cost of adapting to a new physical measurement operator and to limit the requirements for costly labeled data. Here, these challenges are tackled with a frugal and multimodal semantic-EM inversion technique. The key ingredient is a multimodal generator of reconstruction results that can be pretrained, being agnostic to the physical measurement operator. The generator is fed by a multimodal foundation model encoding the multimodal semantic prior and a physical adapter encoding the measured data. For a new physical setting, only the lightweight physical adapter is retrained. The authors' architecture also enables a flexible iterative step-by-step solution to the inverse problem where each step can be semantically controlled. The feasibility and benefits of this methodology are demonstrated for three EM inverse problems: a canonical two-dimensional inverse-scattering problem in numerics, as well as three-dimensional and four-dimensional compressive microwave meta-imaging experiments.

10.
Skin Res Technol ; 30(9): e70053, 2024 09.
Article in English | MEDLINE | ID: mdl-39234634

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is a prevalent chronic inflammatory and highly pruritic skin condition characterized by the infiltration of immune cells, notably eosinophils and mast cells. Mast cells (MCs) critically participate in the complex pathogenesis of AD through multiple pathways and have recently garnered growing attention in research. Despite the abundance of related studies published over the years, a comprehensive bibliometric analysis on this topic remains lacking. OBJECTIVE: Our objective was to perform an up-to-date bibliometric analysis of the literature focusing on the relationship between MCs and AD. This analysis would provide valuable insights through a thorough bibliometric review, enabling a clearer understanding of the current research landscape, pinpointing key studies, and detecting emerging trends within this field. METHODS: We searched the Web of Science Core Collection (WoSCC) database on 15 July 2024. The data retrieval strategy was structured as follows: #1: TS = ("mast cells") OR TS = ("mast cell") OR TS = ("mastocyte"); #2: TS = ("atopic dermatitis") OR TS = ("atopic eczema") Final data: (#1 AND #2). A total of 2272 items published between 2001 and 2024 were included. Several scientometric visualization tools, including VOSviewer, R-bibliometrix, CiteSpace and an online analytical platform, were utilized to conduct text mining and to visualize the bibliometric data, facilitating a comprehensive analysis of research trends and patterns. RESULTS: Out of the initial 2272 articles retrieved, 2168 were selected for analysis after applying inclusion and exclusion criteria based on publication type. The findings indicate a steady and substantial exponential growth in the annual number of publications focused on the relationship between over the years. The South Korea (547/2168), USA (465/2168) and Japan (436/2168) were the major contributors within this field, collectively constituting more than half of the total publications. To clarify the underlying mechanisms and role of MCs in the pathogenesis of AD and to make MCs prime targets for therapeutic intervention have garnered the most attention in this field. According to references analysis, the research emphasis has shifted to developing MC-related therapeutics and intervention and regulating the immune system of AD patients through modulating the activity of various immune cells. On the basis of keywords analysis, we outlined the following research frontiers and hotpots in the future: the role of oxidative stress in the pathogenesis; imbalance in the different types of T helper (Th) cells during immune response; skin barrier and barrier dysfunction; improving quality of life; sensory neurons; biological agents and small-molecule drugs. Furthermore, IL-13, IL-4, NFKB1, BCGF-1 and CD4 ranked as the top five genes that have received the most investigative attention in the intersection of MCs and AD. CONCLUSION: In a word, this analysis would greatly benefit from a thorough bibliometric review to gain a deeper understanding of the current research landscape, identify pivotal studies and pinpoint emerging trends in the field of MCs and AD. Meanwhile, our findings offered researchers a holistic perspective of ongoing developments, serving as a valuable resource for guiding future research and informing decision-making for both researchers and policymakers in this area.


Subject(s)
Bibliometrics , Dermatitis, Atopic , Mast Cells , Dermatitis, Atopic/immunology , Humans , Mast Cells/immunology , Animals
11.
J Am Coll Cardiol ; 84(12): 1092-1103, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39260931

ABSTRACT

BACKGROUND: B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide is the only blood biomarker in established risk calculators for pulmonary arterial hypertension (PAH). Profiling systemic-originated plasma immunoglobulin G (IgG) N-glycans, which reflect different components of the pathophysiology of PAH including immune dysregulation and inflammation, may improve PAH risk assessment. OBJECTIVES: This study sought to identify plasma IgG N-glycan biomarkers that predict survival in PAH to improve risk assessment. METHODS: This cohort study examined 622 PAH patients from 2 national centers (Beijing [discovery] cohort: n = 273; Shanghai [validation] cohort: n = 349). Plasma IgG N-glycomes were profiled by a robust mass spectrometry-based method. Prognostic IgG N-glycan traits were identified and validated in the 2 cohorts using Cox regression and Kaplan-Meier survival analyses. The added value of IgG N-glycan traits to previously established risk models was assessed using Harrell C-indexes and survival analysis. RESULTS: Plasma IgG fucosylation was found to predict survival independent of age and sex in the discovery cohort (HR: 0.377; 95% CI: 0.168-0.845; P = 0.018) with confirmation in the validation cohort (HR: 0.445; 95% CI: 0.264-0.751; P = 0.005). IgG fucosylation remained a robust predictor of mortality in combined cohorts after full adjustment and in subgroup analyses. Integrating IgG fucosylation into previously established risk models improved their predictive capacity, marked by an overall elevation in Harrell C-indexes. IgG fucosylation was useful in further stratifying the intermediate-risk patients classified by a previously established model. CONCLUSIONS: Plasma IgG fucosylation informs PAH prognosis independent of established factors, offering additional value for predicting PAH outcomes.


Subject(s)
Biomarkers , Immunoglobulin G , Humans , Female , Male , Immunoglobulin G/blood , Middle Aged , Prognosis , Biomarkers/blood , Adult , Pulmonary Arterial Hypertension/blood , Pulmonary Arterial Hypertension/mortality , Cohort Studies , Polysaccharides/blood , Aged , Risk Assessment/methods , China/epidemiology
12.
Nat Commun ; 15(1): 7861, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39251585

ABSTRACT

Simultaneously improving the activity and stability of catalysts for anodic oxygen evolution reaction (OER) in proton exchange membrane water electrolysis (PEMWE) remains a notable challenge. Here, we report a chromium-doped ruthenium dioxide with oxygen vacancies, termed Cr0.2Ru0.8O2-x, that drives OER with an overpotential of 170 mV at 10 mA cm-2 and operates stably over 2000 h in acidic media. Experimental and theoretical studies show that the synergy of Cr dopant and oxygen vacancy induces an unconventional dopant-mediated hydroxyl spillover mechanism. Such dynamic hydroxyl spillover from Cr dopant to Ru active site changes the rate-determining step from OOH* formation to O2 formation and thus greatly improves the OER performance. Moreover, the Cr dopant and oxygen vacancy also play a crucial role in stabilizing surface Ru and lattice oxygen in the Ru-O-Cr structural motif. When assembled into the anode of a practical PEMWE device, Cr0.2Ru0.8O2-x enables long-term durability of over 200 h at an ampere-level current density and 60 degrees centigrade.

13.
Sci Rep ; 14(1): 21035, 2024 09 09.
Article in English | MEDLINE | ID: mdl-39251865

ABSTRACT

Human noroviruses (HuNoVs) are a leading cause of acute viral gastroenteritis worldwide. Infectious outbreaks due to recombinant NoV genotype called GII.P16-GII.2 have been frequently reported since 2016. In this study, we expressed the major capsid protein VP1 from three GII.2 NoV strains using the recombinant baculovirus expression system. The assembly, histo-blood group antigen (HBGA)-binding patterns, and cross-blocking abilities of VP1 proteins were investigated. All the three NoV VP1 proteins successfully assembled into virus-like particles (VLPs). The HBGA-binding assay demonstrated a temporal binding pattern. The latest isolate bound to saliva samples of all blood types. Sequence alignment suggested that the observed gain in HBGA-binding ability was attributed to a limited number of amino acid mutations. Using chimeric VP1 proteins, we demonstrated that synergistic effects resulted in enhanced binding ability. Bile salts increased GII.2 VLP avidity for HBGAs except GII.2-2011/M1. In vitro blockade assay of salivary HBGA-VLP binding demonstrated the presence of cross-blocking effects among different strains. This study provides insight into the evolutionary binding characteristics and cross-blocking effects of GII.2 NoVs to facilitate the development of measures to control this type of viruses.


Subject(s)
Blood Group Antigens , Capsid Proteins , Norovirus , Norovirus/genetics , Norovirus/metabolism , Capsid Proteins/genetics , Capsid Proteins/metabolism , Capsid Proteins/immunology , Humans , Blood Group Antigens/metabolism , Caliciviridae Infections/virology , Caliciviridae Infections/immunology , Protein Binding , Genotype , Saliva/virology , Gastroenteritis/virology , Amino Acid Sequence
14.
Clin Chem ; 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39288005

ABSTRACT

BACKGROUND: Due to the diversity of the immune repertoire (IR), reconstructing full-length IR using traditional short-read sequencing has proven challenging. METHODS: A full-length IR sequencing (FLIRseq) work flow was developed with linear rolling circle amplification and nanopore sequencing. Its accuracy and quantification ability were verified by plasmid mixtures and commercial B-cell receptor/T-cell receptor sequencing (BCR/TCR-seq) based on short reads. IRs in tissues and the peripheral blood from 8 patients with acute lymphoblastic leukemia, 3 patients with allergic diseases, 4 patients with psoriasis, and 5 patients with prostate cancer were analyzed using FLIRseq. RESULTS: FLIRseq reads had lower mismatch rates and gap rates, and higher identify rates than nanopore reads (all P < 2.2 × -16). The relative quantification of components by FLIRseq was consistent with the actual quantification (P > 0.05). FLIRseq had superiority over BCR/TCR-seq, providing the long complementarity-determining region 3, B-cell isotype, and the rarely used V gene sequence. FLIRseq observed an increase in clonotype diversity (P < 0.05) and a decrease in the percentage of abnormal BCRs/TCRs in patients with leukemia in remission. For patients with allergic diseases or psoriasis, FLIRseq provided direct insights into V(D)J recombination and specific immunoglobulin classes. Compared with that in prostate cancer tissues, the full-length V segment of the biased T-cell receptor ß chain from lymphocytes in psoriatic tissues showed a more consistent AlphaFold2-predicted protein structure (P < 0.05). CONCLUSIONS: FLIRseq enables unbiased and comprehensive analyses of direct V(D)J recombination and immunoglobulin classes, thereby contributing to characterizing pathogenic mechanisms, monitoring minimal residual disease, and customizing adoptive cell therapy.

15.
Mar Environ Res ; 202: 106744, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39288544

ABSTRACT

Marine pollutants, especially potentially toxic elements (PTEs), increasingly threaten the ecological environment and fishery resources of the Beibu Gulf due to their bioaccumulative nature, toxicity, and persistence. However, the occurrences of multiple PTEs in marine invertebrates within this region remains unclear. Hence, a total of 18 species of commercially harvested invertebrates (shrimp, crab, cephalopod, shellfish, and sea cucumber) were collected from the Beibu Gulf, and the concentrations of nine important PTEs (As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, and Zn) were examined. Subsequent stable isotope analysis for δ13C and δ15N facilitated investigations into biomagnification and human health risk assessment. The results showed that, except for As, the concentrations of the PTEs in the invertebrates were below the national safety limits. Furthermore, significant positive correlations were found between trophic levels (TLs) and log-transformed concentrations of As (P < 0.001, R2 = 0.20) and Cr (P < 0.001, R2 = 0.13), indicating biomagnification of these two metals across trophic positions among species. Finally, the human health risk assessment revealed that the consumption of cephalopod, shellfish, and sea cucumber poses a higher risk of adverse effects compared to shrimp and crab.

17.
Elife ; 132024 Sep 12.
Article in English | MEDLINE | ID: mdl-39264149

ABSTRACT

Familial exudative vitreoretinopathy (FEVR) is a severe genetic disorder characterized by incomplete vascularization of the peripheral retina and associated symptoms that can lead to vision loss. However, the underlying genetic causes of approximately 50% of FEVR cases remain unknown. Here, we report two heterozygous variants in calcyphosine-like gene (CAPSL) that is associated with FEVR. Both variants exhibited compromised CAPSL protein expression. Vascular endothelial cell (EC)-specific inactivation of Capsl resulted in delayed radial/vertical vascular progression, compromised endothelial proliferation/migration, recapitulating the human FEVR phenotypes. CAPSL-depleted human retinal microvascular endothelial cells (HRECs) exhibited impaired tube formation, decreased cell proliferation, disrupted cell polarity establishment, and filopodia/lamellipodia formation, as well as disrupted collective cell migration. Transcriptomic and proteomic profiling revealed that CAPSL abolition inhibited the MYC signaling axis, in which the expression of core MYC targeted genes were profoundly decreased. Furthermore, a combined analysis of CAPSL-depleted HRECs and c-MYC-depleted human umbilical vein endothelial cells uncovered similar transcription patterns. Collectively, this study reports a novel FEVR-associated candidate gene, CAPSL, which provides valuable information for genetic counseling of FEVR. This study also reveals that compromised CAPSL function may cause FEVR through MYC axis, shedding light on the potential involvement of MYC signaling in the pathogenesis of FEVR.


Subject(s)
Familial Exudative Vitreoretinopathies , Humans , Familial Exudative Vitreoretinopathies/genetics , Endothelial Cells/metabolism , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , Animals , Retinal Neovascularization/genetics , Retinal Neovascularization/metabolism , Retinal Neovascularization/pathology , Cell Movement/genetics , Cell Proliferation/genetics , Mice , Retinal Vessels/metabolism , Retinal Vessels/pathology , Male , Neovascularization, Pathologic/genetics , Signal Transduction , Female , Angiogenesis
18.
Food Res Int ; 195: 114984, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39277245

ABSTRACT

This study investigated the impact of processing temperatures (190 °C, 210 °C, and 230 °C) and durations (7 min, 10 min, and 14 min) on the formation of Maillard reaction products (MRPs) and antioxidant activities in pan baked buns. Key Maillard reaction indicators, including glyoxal (GO), methylglyoxal (MGO), 5-hydroxymethylfurfural (5-HMF), melanoidins, and fluorescent advanced glycation end products (AGEs) were quantified. The results demonstrated significant increases in GO, MGO, 5-HMF contents (p < 0.05), and antioxidant activities (p < 0.05) when the buns were baked at 210 °C for 14 min, 230 °C for 10 min and 14 min. However, the interior MRPs of baked buns were minimally affected by the baking temperature and duration. Prolonged heating temperatures and durations exacerbated MRPs production (43.8 %-1038 %) in the bottom crust. Nonetheless, this process promoted the release of bound phenolic compounds and enhanced the antioxidant activity. Heating induces the thermal degradation of macromolecules in food, such as proteins and polysaccharides, which releases bound phenolic compounds by disrupting their chemical bonds within the food matrix. Appropriate selections of baking parameters can effectively reduce the formation of MRPs while simultaneously improve sensory quality and health benefit of the pan baked buns. Considering the balance between higher antioxidant properties and lower MRPs, the optimal thermal parameters for pan baked buns were 210 °C for 10 min. Furthermore, a normalized analysis revealed a consistent trend for GO, MGO, 5-HMF, fluorescent AGEs, and melanoidins. Moreover, MRPs were positively correlated with total contents of phenolic compounds, ferric-reducing antioxidant power (FRAP), and color, but negatively correlated with moisture contents and reducing sugars. Additionally, the interaction between baking conditions and Maillard reactions probably contributed to enhanced primary flavors in the final product. This study highlights the importance of optimizing baking parameters to achieve desirable MRPs levels, higher antioxidant activity, and optimal sensory attributes in baked buns.


Subject(s)
Antioxidants , Cooking , Furaldehyde , Glycation End Products, Advanced , Hot Temperature , Maillard Reaction , Pyruvaldehyde , Antioxidants/analysis , Antioxidants/chemistry , Furaldehyde/analogs & derivatives , Furaldehyde/analysis , Furaldehyde/chemistry , Pyruvaldehyde/chemistry , Cooking/methods , Humans , Glyoxal/chemistry , Taste , Polymers/chemistry , Bread/analysis
19.
J Ethnopharmacol ; 337(Pt 1): 118815, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39270882

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese herbal medicines (TCHM) have been extensively used in China and other East and Southeast Asian countries. Due to the low content of bioactive components in most TCHM and the potential toxicity of some herbal ingredients to humans, researchers have turned to probiotic fermentation to enhance the efficacy, mitigate the toxic or side effects and improve the taste of TCHM. Both probiotics and certain TCHM benefit the intestinal microbiota and intestinal barrier of human body, demonstrating synergistic effects on in intestinal microecology. AIM OF THE STUDY: This review aims to provide an overview of the development of fermentation technology, commonly used probiotic strains for TCHM fermentation, the advantages of probiotic fermentation and the challenges and limitations of probiotic-fermented TCHM. Additionally, it summarises and discusses the impact of probiotic-fermented TCHM on the intestinal barrier and microbiota, as well as the possible mechanisms involved. MATERIALS AND METHODS: An extensive search of primary literature was conducted using various databases including PubMed, Google Scholar, Web of Science, Elsevier, SpringerLink, ScienceDirect, CNKI, and others. All the plant names have been checked with World Flora Online (http://www.worldfloraonline.org) on August 7, 2024. RESULTS: The literature mentioned above was analyzed and summarized comprehensively. Probiotic-fermented TCHM can improve the intestinal barrier, modulate gut microbiota, and maintain homeostasis of the intestinal microecology. Modulating intestinal microecology by probiotic-fermented TCHM may be a crucial mechanism for its beneficial effects. CONCLUSIONS: This article establishes a theoretical basis for further research on the relationship between probiotic-fermented TCHM and the intestinal microecology, with the hope of inspiring innovative concepts for the development of TCHM and exploring the potential of probiotic-fermented TCHM as a promising strategy for maintaining intestinal microecological balance.

20.
Quant Imaging Med Surg ; 14(9): 6734-6744, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39281138

ABSTRACT

Background: Targeted therapy with neoadjuvant chemotherapy for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer has increased the rates of pathological complete response (pCR) and breast preservation surgery and improved the overall disease-free survival rate. This study aimed to determine whether tumor enhancement and shrinkage patterns in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can predict the efficacy of targeted therapy in patients with HER2-positive breast cancer and differentiate pCR from non-pCR. Methods: The data of 64 patients with HER2-positive breast cancer who received targeted therapy prior to surgery were retrospectively collected. All patients had complete postoperative pathological data. The pretreatment evaluation of the tumor enhancement pattern and the shrinkage pattern after two treatment cycles were assessed. The difference in the enhancement and shrinkage patterns between the pCR and non-pCR groups was evaluated via the χ2 test. Logistic regression analysis was used to assess the value of enhancement and shrinkage patterns for predicting pCR in patients with HER2-positive breast cancer. Results: There were statistically significant differences in tumor size, estrogen receptor (ER) status, lymph node metastasis, enhancement pattern, and shrinkage pattern between the pCR and non-pCR cases. Patients with a tumor size ≤20 mm were likely to achieve pCR. ER status, lymph node metastasis, and enhancement and shrinkage patterns each had good precision for predicting pCR, and the combination of enhancement and shrinkage patterns had the highest prediction accuracy. Multivariate logistic regression analysis indicated that only enhancement pattern had a significant predictive value. Conclusions: Among patients with HER2-positive breast cancer, those with tumor size ≤20 mm, ER-negative status, no lymph node metastases, and mass enhancement and concentric shrinkage patterns are more likely to achieve pCR. Mass enhancement combined with concentric shrinkage had the highest accuracy in predicting pCR, indicating that preoperative imaging may be useful for guiding clinical decisions regarding targeted treatments.

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