Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 3.040
Filter
1.
J Biomed Opt ; 30(Suppl 1): S13702, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39034960

ABSTRACT

Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety. Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues. Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D. Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels. Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.


Subject(s)
Optical Imaging , Parathyroid Glands , Spectroscopy, Near-Infrared , Thyroidectomy , Humans , Parathyroid Glands/surgery , Parathyroid Glands/metabolism , Male , Female , Middle Aged , Optical Imaging/methods , Adult , Spectroscopy, Near-Infrared/methods , Paraffin Embedding/methods , Aged , Thyroid Cancer, Papillary/surgery , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/metabolism , Receptors, Calcium-Sensing/metabolism , Receptors, Calcium-Sensing/analysis
2.
Nanoscale ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39225229

ABSTRACT

Theoretically determining the lowest-energy structure of a cluster has been a persistent challenge due to the inherent difficulty in accurate description of its potential energy surface (PES) and the exponentially increasing number of local minima on the PES with the cluster size. In this work, density-functional theory (DFT) calculations of Co clusters were performed to construct a dataset for training deep neural networks to deduce a deep potential (DP) model with near-DFT accuracy while significantly reducing computational consumption comparable to classic empirical potentials. Leveraging the DP model, a high-efficiency hybrid differential evolution (HDE) algorithm was employed to search for the lowest-energy structures of CoN (N = 11-50) clusters. Our results revealed 38 of these clusters superior to those recorded in the Cambridge Cluster Database and identified diverse architectures of the clusters, evolving from layered structures for N = 11-27 to Marks decahedron-like structures for N = 28-42 and to icosahedron-like structures for N = 43-50. Subsequent analyses of the atomic arrangement, structural similarity, and growth pattern further verified their hierarchical structures. Meanwhile, several highly stable clusters, i.e., Co13, Co19, Co22, Co39, and Co43, were discovered by the energetic analyses. Furthermore, the magnetic stability of the clusters was verified, and a competition between the coordination number and bond length in affecting the magnetic moment was observed. Our study provides high-accuracy and high-efficiency prediction of the optimal structures of clusters and sheds light on the growth trend of Co clusters containing tens of atoms, contributing to advancing the global optimization algorithms for effective determination of cluster structures.

3.
Eur J Med Chem ; 278: 116792, 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39217861

ABSTRACT

Enhancing the efficacy of subunit vaccines relies significantly on the utilization of potent adjuvants, particularly those capable of triggering multiple immune pathways. To achieve synergistic immune augmentation by Toll-like receptor 4 agonist (TLR4a) and nucleotide-binding oligomerization-domain-containing protein 2 agonist (NOD2a), in this work, we conjugated RC529 (TLR4a) and MDP (NOD2a) to give RC529-MDP, and evaluated its adjuvanticity for OVA antigen. Compared to the unconjugated RC529+MDP, RC529-MDP remarkably enhanced innate immune responses with 6.8-fold increase in IL-6 cytokine, and promoted the maturation of antigen-presenting cells (APCs), possibly because of the conjugation of multiple agonists ensuring their delivery to the same cell and activation of various signaling pathways within that cell. Furthermore, RC529-MDP improved OVA-specific antibody response, T cells response and the memory T cells ratio relative to the unconjugated mixture. Therefore, covalently conjugating TLR4 agonist and NOD2 agonist was an effective strategy to enhance immune responses, providing the potential to design and develop more effective vaccines.

4.
Transplant Proc ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39232922

ABSTRACT

BACKGROUND: Reactivation of cytomegalovirus (CMV) is typically considered harmless as long as the immune system remains unaffected by medications or other factors. CMV reactivation may occur as a result of acute graft-versus-host disease of Grades II to IV. One possible factor contributing to this risk is the rise in the number of donors who lack genetic similarities or relationships. We hypothesized that the anti-CMV IgG level before transplantation could potentially serve as an indicator of the likelihood of CMV reactivation following hematopoietic cell transplantation. METHODS: We examined a cohort of young individuals who underwent allogeneic HCT between 1998 and 2022 to evaluate the occurrence of CMV reactivation. The patients were divided into 2 time periods: 1998 to 2016 (comparison group) and 2017 to 2022 (intervention group). RESULTS: Between 1998 and 2016, 292 patients underwent hematopoietic HCT. Recipients from 2017 to 2022 experienced a slightly higher risk of CMV reactivation than those from 1998 to 2016. The comparison of prophylactic and preemptive medication showed no significant difference between the periods (P = .32). Patients treated from 1998 to 2016 experienced a 23% decrease in the risk of symptomatic CMV reactivation and related illnesses compared to those treated from 2017 to 2022 (P = .08 and .15, respectively). CONCLUSIONS: Our study showed that the intervention group had more symptomatic CMV reactivations. Various factors may contribute to this, including CD19-directed immunotherapy and the CMV status of the recipient before transplantation.

5.
Acta Pharmacol Sin ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39227736

ABSTRACT

Emerging evidence shows that psychological stress promotes the progression of Parkinson's disease (PD) and the onset of dyskinesia in non-PD individuals, highlighting a potential avenue for therapeutic intervention. We previously reported that chronic restraint-induced psychological stress precipitated the onset of parkinsonism in 10-month-old transgenic mice expressing mutant human α-synuclein (αSyn) (hαSyn A53T). We refer to these as chronic stress-genetic susceptibility (CSGS) PD model mice. In this study we investigated whether ginsenoside Rg1, a principal compound in ginseng notable for soothing the mind, could alleviate PD deterioration induced by psychological stress. Ten-month-old transgenic hαSyn A53T mice were subjected to 4 weeks' restraint stress to simulate chronic stress conditions that worsen PD, meanwhile the mice were treated with Rg1 (40 mg· kg-1 ·d-1, i.g.), and followed by functional magnetic resonance imaging (fMRI) and a variety of neurobehavioral tests. We showed that treatment with Rg1 significantly alleviated both motor and non-motor symptoms associated with PD. Functional MRI revealed that Rg1 treatment enhanced connectivity between brain regions implicated in PD, and in vivo multi-channel electrophysiological assay showed improvements in dyskinesia-related electrical activity. In addition, Rg1 treatment significantly attenuated the degeneration of dopaminergic neurons and reduced the pathological aggregation of αSyn in the striatum and SNc. We revealed that Rg1 treatment selectively reduced the level of the stress-sensitive protein RTP801 in SNc under chronic stress conditions, without impacting the acute stress response. HPLC-MS/MS analysis coupled with site-directed mutation showed that Rg1 promoted the ubiquitination and subsequent degradation of RTP801 at residues K188 and K218, a process mediated by the Parkin RING2 domain. Utilizing αSyn A53T+; RTP801-/- mice, we confirmed the critical role of RTP801 in stress-aggravated PD and its necessity for Rg1's protective effects. Moreover, Rg1 alleviated obstacles in αSyn autophagic degradation by ameliorating the RTP801-TXNIP-mediated deficiency of ATP13A2. Collectively, our results suggest that ginsenoside Rg1 holds promise as a therapeutic choice for treating PD-sensitive individuals who especially experience high levels of stress and self-imposed expectations.

6.
Nutr Health ; : 2601060241277579, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39234642

ABSTRACT

This study aimed to explore the relationship between food intake frequency, weight status, and intelligence among school children. A cross-sectional study involved 562 children (aged 6.3-12.7 years) randomly selected from five elementary schools in Taichung City, Taiwan. Demographic information was collected, and the children's body weight and height were measured to calculate their body mass index. A food frequency questionnaire assessed the participating children's dietary habits. Intelligence quotient scores were evaluated using Raven's colored progress matrices for first and second graders, and Raven's standard progressive matrices for third to sixth graders. This study found that there was no significant relationship in intelligence quotient scores between gender, birth order groups, and weight status. The higher consumption of pork liver, hamburgers, fruit juices, and the Taiwanese snack "Science Noodles" was associated with lower intelligence quotient scores among school children.

7.
Phys Rev E ; 110(1-1): 014132, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39160973

ABSTRACT

The fluctuation of the quantum Otto engine has recently received a lot of attention, while applying the many body with a long-range interaction to a quantum heat engine may enhance our ability of controlling it. Using the two-point measurement and its generalization, we explore the fluctuation theorem of work and heat in a single stroke as well as in a cycle. We discover that the fluctuations of work in a cycle as well as fluctuations of heat in a single stroke or cycle can be connected to the fluctuation of work in a single stroke. Then we numerically investigate the effect of a long-range interaction on these fluctuation theorems, and our result shows that the fluctuation can be improved by manipulating the long-range interaction.

8.
Curr Neurovasc Res ; 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39092730

ABSTRACT

BACKGROUND: Glioblastoma multiforme (GBM) is an aggressive type of brain tumor that is difficult to remove surgically. Research suggests that substances from saffron, namely crocetin and crocin, could be effective natural treatments, showing abilities to kill cancer cells. METHODS: Our study focused on evaluating the effects of crocetin on glioma using the U87 cell line. We specifically investigated how crocetin affects the survival, growth, and spread of glioma cells, exploring its impact at concentrations ranging from 75-150 µM. The study also included experiments combining crocetin with the chemotherapy drug Temozolomide (TMZ) to assess potential synergistic effects. RESULTS: Crocetin significantly reduced the viability, proliferation, and migration of glioma cells. It achieved these effects by decreasing the levels of Matrix Metallopeptidase 9 (MMP-9) and Ras homolog family member A (RhoA), proteins that are critical for cancer progression. Additionally, crocetin inhibited the formation of cellular structures necessary for tumor growth. It blocked multiple points of the Ak Strain Transforming (AKT) signaling pathway, which is vital for cancer cell survival. This treatment led to increased cell death and disrupted the cell cycle in the glioma cells. When used in combination with TMZ, crocetin not only enhanced the reduction of cancer cell growth but also promoted cell death and reduced cell replication. This combination therapy further decreased levels of high mobility group box 1 (HMGB1) and Receptor for Advanced Glycation End-products (RAGE), proteins linked to inflammation and tumor progression. It selectively inhibited certain pathways involved in the cellular stress response without affecting others. CONCLUSION: Our results underscore the potential of crocetin as a treatment for glioma. It targets various mechanisms involved in tumor growth and spread, offering multiple avenues for therapy. Further studies are essential to fully understand and utilize crocetin's benefits in treating glioma.

9.
Cancer Med ; 13(15): e70061, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39101462

ABSTRACT

BACKGROUND: While surgery remains the primary treatment for oral squamous cell carcinoma (OCSCC), induction chemotherapy (IC) can be used as a bridging or neoadjuvant therapy. This nationwide study in Taiwan examines the survival outcomes of OCSCC patients who received IC before surgery. METHODS: We analyzed data from 29,891 patients with OCSCC. Of these, 29,058 initially underwent surgery (OP group), whereas 833 received IC before surgery (IC + OP group). A propensity score (PS)-matched analysis (4, 1 ratio, 3260 vs. 815 patients) was performed considering tumor subsite, sex, age, Charlson comorbidity index, clinical T1-T4b tumors, clinical N0-3 disease, and clinical stage I-IV. RESULTS: In the PS-matched cohort, the 5-year disease-specific survival (DSS) and overall survival (OS) rates were 65% and 57%, respectively. When comparing the OP and IC + OP groups, the 5-year DSS rates were 66% and 62%, respectively (p = 0.1162). Additionally, the 5-year OS rates were 57% and 56%, respectively (p = 0.9917). No significant intergroup differences in survival were observed for specific subgroups with cT4a tumors, cT4b tumors, cN3 disease, pT4b tumors, and pN3 disease. However, for patients with pT4a tumors, the OP group demonstrated superior 5-year outcomes compared to the IC + OP group, with a DSS of 62% versus 52% (p = 0.0006) and an OS of 53% versus 44% (p = 0.0060). Notably, patients with cT2-3, cN1, and c-Stage II disease in the IC + OP group were significantly more likely to achieve pT0-1 status (p < 0.05). CONCLUSIONS: Following PS matching, the IC + OP group generally exhibited similar prognosis to the OP group. However, for pT4a tumors, the OP group showed superior 5-year outcomes. While IC may not universally improve survival, it could be advantageous for patients who respond positively to the treatment.


Subject(s)
Induction Chemotherapy , Mouth Neoplasms , Neoadjuvant Therapy , Humans , Male , Female , Mouth Neoplasms/mortality , Mouth Neoplasms/drug therapy , Mouth Neoplasms/surgery , Mouth Neoplasms/pathology , Mouth Neoplasms/therapy , Neoadjuvant Therapy/methods , Middle Aged , Prognosis , Aged , Taiwan/epidemiology , Adult , Neoplasm Staging , Cohort Studies , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
10.
Front Public Health ; 12: 1437647, 2024.
Article in English | MEDLINE | ID: mdl-39091532

ABSTRACT

Introduction: How to scientifically assess the health status of cities and effectively assist in formulating policies and planning for health city development remains a profound challenge in building a global "health community." Methods: This study employs the Building Research Establishment's International Healthy Cities Index (BRE HCI), encompassing ten environmental categories and fifty-eight indicators, to guide and support the scientific development of healthy cities. The entropy weight-TOPSIS method and the rank sum ratio (RSR) method were applied to comprehensively rank and categorize the health development levels of fifteen global cities. Furthermore, through cluster analysis, this research identifies universal and unique indicators that influence the development of healthy cities. Results: The results indicate that: (1) Within the scope of 58 evaluation indicators, the precedence in weight allocation is accorded to the kilometres of bicycle paths and lanes per 100,000 population (0.068), succeeded by m2 of public indoor recreation space per capita (0.047), and kilometres of bicycle paths and lanes per 100,000 population (0.042). (2) Among the ten environmental categories, the top three in terms of weight ranking are transport (0.239), leisure and recreation (0.172), and resilience (0.125). Significant disparities exist between different cities and environmental categories, with the issue of uneven health development within cities being particularly prominent. (3) The study categorizes the development levels of healthy cities into three tiers based on composite scores: it classifies Singapore, Shanghai, and Amsterdam at an excellent level; places Dubai and Johannesburg at a comparatively poor level; and situates the remaining ten cities at a moderate level. (4) The analysis identifies 53 international common indicators and 5 characteristic indicators from the 58 indicators based on the significance of the clustering analysis (p < 0.05). Discussion: The study proposes four strategic recommendations based on these findings: establishing a comprehensive policy assurance system, refining urban spatial planning, expanding avenues for multi-party participation, and augmenting distinctive health indicators. These measures aim to narrow the developmental disparities between cities and contribute to healthy global cities' balanced and sustainable growth. However, due to existing limitations in sample selection, research methodology application, and the control of potential confounding variables, further in-depth studies are required in the future.


Subject(s)
Cities , Global Health , Humans , City Planning , Urban Health
11.
Medicine (Baltimore) ; 103(33): e39446, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39151495

ABSTRACT

RATIONALE: This study reports the first case of congenital hypothyroidism (CH) and alpha thalassemia in a child in China, with anemia and muscle damage as the main manifestations. Analyzing and studying this case is of great significance in reducing missed and misdiagnosed CH and will provide a clinical strategy for treating these patients. PATIENT CONCERNS: Child, female, 2 years and 7 months old, the child appeared dispirited, had poor appetite, shallow complexion, reduced activities with anemia, elevated muscle enzymes, height, and growth retardation. DIAGNOSES: The child was diagnosed with CH with alpha thalassemia. INTERVENTIONS: The patient was treated with levothyroxine sodium and anemia correction. OUTCOMES: The children's current spirit, appetite, red face, normal limb activity, physical development, and intelligence were significantly better than those of normal children of the same age. CONCLUSIONS: CH with alpha thalassemia, especially anemia and muscle damage as the main manifestations, has not been reported. Administration of levothyroxine sodium is effective in correcting anemia in patients with CH and alpha thalassemia. LESSON: Due to CH and alpha thalassemia, there are no specific symptoms and they are prone to missed diagnosis and misdiagnosis. Therefore, patients with anemia and elevated muscle enzyme levels should be routinely tested for thyroid function to diagnose them early and provide proper treatment to avoid negative consequences.


Subject(s)
Anemia , Congenital Hypothyroidism , Thyroxine , alpha-Thalassemia , Humans , Female , alpha-Thalassemia/complications , alpha-Thalassemia/diagnosis , Congenital Hypothyroidism/complications , Congenital Hypothyroidism/diagnosis , Congenital Hypothyroidism/drug therapy , Child, Preschool , Thyroxine/therapeutic use , Anemia/etiology , Anemia/drug therapy , Muscular Diseases/etiology , Muscular Diseases/diagnosis , Muscular Diseases/complications
12.
J Diabetes Complications ; 38(10): 108848, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39178624

ABSTRACT

Diabetes is a major risk factor for cardiovascular diseases, and myocardial damage caused by hyperglycemia is the main cause of heart failure. However, there is still a lack of systematic understanding of myocardial damage caused by diabetes. At present, we believe that the cellular inflammatory damage caused by hyperglycemia is one of the causes of diabetic cardiomyopathy. Pyroptosis, as a proinflammatory form of cell death, is closely related to the occurrence and development of diabetic cardiomyopathy. Therefore, this paper focuses on the important role of inflammation in the occurrence and development of diabetic cardiomyopathy. From the perspective of pyroptosis, we summarize the pyroptosis of different types of cells in diabetic cardiomyopathy and its related signaling pathways. It also summarizes the treatment of diabetic cardiomyopathy, hoping to provide methods for the prevention and treatment of diabetic cardiomyopathy by inhibiting pyroptosis.

13.
Org Lett ; 26(33): 6939-6943, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39158203

ABSTRACT

Herein, we introduce an electrochemical dehydrogenative [3 + 2]/[5 + 2] annulation of easily available N-arylacrylamides with γ,σ-unsaturated malonates through C(sp3)-H/C(sp2)-H functionalization. The employment of inexpensive ferrocene as the redox catalyst allows access to diverse benzo[b]azepin-2-ones in moderate to excellent yields without stoichiometric oxidants. This protocol features broad substrate scope and excellent selectivity, and mechanistic studies indicated that the reaction proceeded through the oxidation of a C(sp3)-H bond to generate an alkyl radical, radical addition across the C═C bond, [3 + 2]/[5 + 2] annulations, and C(sp2)-H functionalization cascades.

14.
J Int Med Res ; 52(8): 3000605241259764, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39142703

ABSTRACT

Nodular fasciitis (NF) is a benign and self-limiting fibroblastic proliferation that originates from the superficial fascia and extends into the subcutaneous tissue or muscle. It typically manifests in individuals aged 20 to 35 years, with rare occurrences observed in patients over the age of 60 years. We herein report a case involving a 75-year-old man with NF in the right vocal cord. The patient sought medical attention at the Department of Otolaryngology of our hospital because of a 1-month history of hoarseness and breathlessness. The diagnosis was unable to be confirmed through preoperative pathological examination. After admission to our hospital, various examinations were completed and surgical treatment was performed, and the postoperative histopathological findings revealed the presence of NF in the right vocal cord. NF of the vocal cord is a rare clinical entity. Given its rapid progression and propensity for marked infiltration, it often poses diagnostic challenges because it can mimic various malignant soft tissue tumors. Therefore, thorough exclusion of other neoplastic lesions is imperative prior to confirming the diagnosis of NF through pathological examination. Local surgical resection remains the primary treatment modality.


Subject(s)
Fasciitis , Humans , Male , Fasciitis/diagnosis , Fasciitis/surgery , Fasciitis/pathology , Aged , Vocal Cords/pathology , Vocal Cords/surgery , Hoarseness/etiology , Hoarseness/diagnosis , Diagnosis, Differential
15.
Sci Adv ; 10(33): eado2741, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39150997

ABSTRACT

The standard of clinical care of most malignant solid cancers is surgery, followed by postsurgical adjuvant therapy, but microtumor lesions left behind after surgery and invisible distant metastases are the major reasons for treatment failure. Here, we report an integrated strategy combining surface-enhanced Raman spectroscopy (SERS) surgical navigation with postsurgical immunotherapy elicited by near-infrared II photothermal treatment and programmed death-1 antibody. The SERS surgical navigation is principally based on the multifunctional optical probes (namely, MATRA probes) integrating with T1-weighted magnetic resonance (MR) imaging, photothermal effect and Raman spectroscopic detection. We demonstrate in a 4T1 breast tumor mouse model that the pre-surgical MR/SERS dual-modal imaging is capable of providing comprehensive tumor information, and intraoperative SERS detection allows accurately delineating the tumor margins and guiding the surgical resection in real time with the least residual microscopic foci. We verify that the postsurgical immunotherapy effectively eradicates those local microtumor lesions and invisible distant metastases, greatly inhibiting the postsurgical cancer recurrence and distant metastasis.


Subject(s)
Immunotherapy , Spectrum Analysis, Raman , Animals , Mice , Spectrum Analysis, Raman/methods , Immunotherapy/methods , Female , Cell Line, Tumor , Neoplasm Metastasis , Programmed Cell Death 1 Receptor/immunology , Programmed Cell Death 1 Receptor/metabolism , Magnetic Resonance Imaging/methods , Humans , Mice, Inbred BALB C , Breast Neoplasms/pathology , Breast Neoplasms/immunology , Breast Neoplasms/therapy , Breast Neoplasms/surgery , Disease Models, Animal , Surgery, Computer-Assisted/methods
16.
Int J Biol Macromol ; 278(Pt 1): 134620, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39127274

ABSTRACT

Protein-based subunit vaccines are weakly immunogenic, and developing self-adjuvanting vaccines with adjuvant conjugated to antigen is a promising approach for generating optimal immune responses. Here, we report a novel adjuvant-protein conjugate vaccine based on versatile oxime ligation technique. Firstly, the adjuvant properties of a series of TLR7 and TLR7/8 small molecule agonists in self-adjuvanting vaccines were systematically compared by coupling them to proteins in consistent ratio via p-carboxybenzaldehyde (p-CBA) for the first time. All conjugate vaccines induced cytokine secretion in murine and human macrophages in vitro, and promoted specific antibody production in vivo. Notably, a conjugate containing imidazoquinoline TLR7/8 agonist (TLR7/8a1) showed the greatest enhancement in Th1/2 balanced antibody response. To minimize the interference with the protein antigenic integrity, we further developed a systematic glycoconjugation strategy to conjugate this TLR7/8a1 onto the glycan chains of SARS-CoV-2 S1 glycoprotein via oxime ligation, in which S1 containing different numbers of aldehyde groups were obtained by differential periodate oxidation. The resulting TLR7/8a1-S1 conjugate triggered a potent humoral and cellular immunity in vivo. Together these data demonstrate the promise of these TLR7 and TLR7/8 agonists as effective built-in adjuvants, and the versatile oxime ligation strategy might broaden potential applications in designing different conjugate vaccines.

17.
Phytochemistry ; 228: 114242, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39127394

ABSTRACT

The phytochemical investigation on the pericarps of Garcinia multiflora resulted in the isolation of 12 previously undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs, 1-12) with a variety of skeletons. Their structures were determined by comprehensive spectroscopic analyses, ECD calculations, and single-crystal X-ray diffraction. Compounds 6-9 possess a rare bicyclo[4.3.1]decane skeleton. Additionally, the anti-tumor activity of the 12 isolates was evaluated. The results indicated that compounds 5, 9, and 12 exhibited significant cytotoxicity in a wide range of cancer cell lines, including the human breast cancer MDA-MB-231 cells, human lung cancer A549 cells, human colon cancer SW480 cells and human ovarian cancer HEY cells. Further studies indicated that compound 5 induced cell cycle arrest and apoptosis, to inhibit the growth of MDA-MB-231 cells. Taken together, these findings expand the chemical diversity of PPAPs and further demonstrate the potential of PPAPs as candidates for cancer treatment.

18.
Front Med (Lausanne) ; 11: 1391057, 2024.
Article in English | MEDLINE | ID: mdl-39144664

ABSTRACT

Objective: This study aims to explore the relationship between cardiovascular calcification (CVC) and serum levels of high-density lipoprotein cholesterol (HDL-C) and its subfractions in hemodialysis (HD) patients. Methods: HD patients and healthy participants were recruited based on specific inclusion and exclusion criteria. Various blood indicators were measured, and demographic information was recorded. HDL-C particle levels were quantified using lipophilic fluorescent dye staining and capillary electrophoresis (microfluidic platform). Coronary artery calcium scores and valve calcification were used to classify HD patients into calcification and non-calcification groups. Results: Compared to healthy participants, HD patients showed a significant increase in HDL-C, high-density lipoprotein 2 cholesterol (HDL2-C), and high-density lipoprotein 3 cholesterol (HDL3-C) levels (p < 0.001). Further division of HD patients into calcification and non-calcification groups revealed higher serum HDL3-C concentrations (p = 0.002) and a higher HDL3-C/HDL-C ratio (p = 0.04) in the calcification group. Additionally, elevated HDL3-C levels were found to be an independent risk factor for CVC in HD patients (p = 0.040). The ROC curve analysis showed an AUC value of 0.706 for HDL3-C (p = 0.002). Conclusion: Our study indicates that elevated serum HDL3-C levels in HD patients are an independent risk factor for CVC and can serve as a potential predictor for CVC events. However, more studies need to verify its potential as a predictive indicator..

19.
J Hazard Mater ; 478: 135526, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39153300

ABSTRACT

Phenol and p-cresol are two common toxic small molecules related to various diseases. Existing reports confirmed that high L-tyrosine in the daily diet can increase the concentration of phenolic compounds in blood and urine. L-tyrosine is a common component of protein-rich foods. Some anaerobic bacteria in the gut can convert non-toxic l-tyrosine into these two toxic phenolic compounds, phenol and p-cresol. Existing methods have been constructed for measuring the concentration of phenolic compound in feces. However, there is still a lack of direct visual evidence to measure the phenolic compounds in the intestine. In this study, we aimed to construct a whole-cell biosensor for phenolic compounds detection based on the dmpR, the regulator from the phenol metabolism cluster. The commensal bacterium Citrobacter amalonaticus PS01 was selected and used as the chassis. Compared with the biosensor based on ECN1917, the biosensor PS01[dmpR] could better implant into the mouse gut through gavage and showed a higher sensitive to phenolic compound. And the concentration of phenolic compounds in the intestines could be observed with the help of in vivo imaging system using PS01[dmpR]. This paper demonstrated endogenous phenol synthesis in the gut and the strategy of using commensal bacteria to construct whole-cell biosensors for detecting small molecule compounds in the intestines.

20.
World J Gastrointest Oncol ; 16(8): 3732-3737, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39171188

ABSTRACT

The primary aim of this study was to analyze the evolving trends and key focal points in research on cellular metabolism of colorectal cancer (CRC). Relevant publications on cellular metabolism in CRC were sourced from the Science Citation Index Expanded within the Web of Science Core Collection database. Bibliometric analysis and visualization were conducted using VOSviewer (version 1.6.18) software and CiteSpace 6.1.R6 (64-bit) Basic. A comprehensive compilation of 4722 English-language publications, covering the period from January 1, 1991 to December 31, 2022, was carefully identified and included in the analysis. Among the authors, "Ogino, Shuji" contributed the most publications in this field, while "Giovannucci, E" garnered the highest number of citations. The journal "Cancer Research" ranked first in both publication volume and citations. Institutionally, "Shanghai Jiao Tong University" emerged as the top contributor in terms of published articles, while "Harvard University" led in citation impact. In country-based analysis, the United States held the top position in both publication output and citations, closely followed by China. The increasing recognition of the significance of cellular metabolism in CRC underscores its potential for novel therapeutic approaches aimed at improving CRC management and prognosis.

SELECTION OF CITATIONS
SEARCH DETAIL