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1.
Cancer Med ; 13(11): e7319, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38819606

ABSTRACT

AIM: This study aims to investigate α-fetoprotein (AFP) trajectories for prediction of survival outcomes after hepatic arterial infusion chemotherapy (HAIC) treatment in large hepatocellular carcinoma (HCC). METHODS: From May 2014 to June 2020, 889 eligible patients with large HCC underwent HAIC were retrospectively enrolled from five hospitals. A latent class growth mixed (LCGM) model was applied to distinguish potential AFP level dynamic changing trajectories. Inverse-probability-of-treatment weighted (IPTW) analyses were performed to eliminate unmeasured confounders through marginal structural models. Multivariate Cox proportional hazard regression analyses were used to determine the overall survival (OS) in patients with large HCC. Performance of these serum markers for survival prediction was compared by areas under receiver operating characteristic analysis with the Delong test. RESULTS: The median follow-up time was 23.7 (interquartile range, 3.8-115.3). A total of 1009 patients with large HCC, who underwent HAIC with AFP repeatedly measured 3-10 times, were enrolled in the study. Three distinct trajectories of these serum AFP were identified using the LCGM model: high stable (37.0%; n = 373), low stable (15.7%; n = 159), and sharp-falling (47.3%; n = 477). Multivariate Cox proportional hazard regression analyses found that ALBI stage 2-3, BCLC-C stage and high-stable AFP trajectories were associated with OS. AFP trajectories yield the optimal predictive performance in all risk factors. CONCLUSIONS: The AFP trajectories based on longitudinal AFP change showed outstanding performance for predicting survival outcomes after HAIC treatment in large HCC, which provide a potential monitoring tool for improving clinical decision-making.


Subject(s)
Carcinoma, Hepatocellular , Infusions, Intra-Arterial , Liver Neoplasms , alpha-Fetoproteins , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/blood , Liver Neoplasms/mortality , Liver Neoplasms/pathology , alpha-Fetoproteins/metabolism , alpha-Fetoproteins/analysis , Male , Female , Middle Aged , Retrospective Studies , Longitudinal Studies , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hepatic Artery , Biomarkers, Tumor/blood , Treatment Outcome , Prognosis
2.
J Chem Phys ; 160(14)2024 Apr 14.
Article in English | MEDLINE | ID: mdl-38606736

ABSTRACT

Two-dimensional (2D) transition metal dichalcogenides have emerged as promising quantum functional blocks benefitting from their unique combination of spin, valley, and layer degrees of freedom, particularly for the tremendous flexibility of moiré superlattices formed by van der Waals stacking. These degrees of freedom coupled with the enhanced Coulomb interaction in 2D structures allow excitons to serve as on-chip information carriers. However, excitons are spatially circumscribed due to their low mobility and limited lifetime. One way to overcome these limitations is through the coupling of excitons with surface plasmon polaritons (SPPs), which facilitates an interaction between remote quantum states. Here, we showcase the successful coupling of SPPs with interlayer excitons in molybdenum diselenide/tungsten diselenide heterobilayers. Our results indicate that the valley polarization can be efficiently transferred to SPPs, enabling preservation of polarization information even after propagating tens of micrometers.

3.
Urolithiasis ; 52(1): 63, 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38613670

ABSTRACT

This study aims to elucidate the mechanism and potential of Rhizoma alismatis polysaccharides (RAPs) in preventing oxidative damage to human renal proximal tubule epithelial cells. The experimental approach involved incubating HK-2 cells with 100 nm calcium oxalate monohydrate for 24 h to establish a cellular injury model. Protection was provided by RAPs with varying carboxyl group contents: 3.57%, 7.79%, 10.84%, and 15.33%. The safeguarding effect of RAPs was evaluated by analyzing relevant cellular biochemical indicators. Findings demonstrate that RAPs exhibit notable antioxidative properties. They effectively diminish the release of reactive oxygen species, lactate dehydrogenase, and malondialdehyde, a lipid oxidation byproduct. Moreover, RAPs enhance superoxide dismutase activity and mitochondrial membrane potential while attenuating the permeability of the mitochondrial permeability transition pore. Additionally, RAPs significantly reduce levels of inflammatory factors, including NLRP3, TNF-α, IL-6, and NO. This reduction corresponds to the inhibition of overproduced pro-inflammatory mediator nitric oxide and the caspase 3 enzyme, leading to a reduction in cellular apoptosis. RAPs also display the ability to suppress the expression of the HK-2 cell surface adhesion molecule CD44. The observed results collectively underscore the substantial anti-inflammatory and anti-apoptotic potential of all four RAPs. Moreover, their capacity to modulate the expression of cell surface adhesion molecules highlights their potential in inhibiting the formation of kidney stones. Notably, RAP3, boasting the highest carboxyl group content, emerges as the most potent agent in this regard.


Subject(s)
Calcium Oxalate , Kidney Calculi , Humans , Oxidative Stress , Inflammation/drug therapy , Epithelial Cells , Kidney Calculi/drug therapy , Kidney Calculi/prevention & control
4.
Angew Chem Int Ed Engl ; : e202400441, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38587149

ABSTRACT

Nickel-catalyzed transannulation reactions triggered by the extrusion of small gaseous molecules have emerged as a powerful strategy for the efficient construction of heterocyclic compounds. However, their use in asymmetric synthesis remains challenging because of the difficulty in controlling stereo- and regioselectivity. Herein, we report the first nickel-catalyzed asymmetric synthesis of N-N atropisomers by the denitrogenative transannulation of benzotriazones with alkynes. A broad range of N-N atropisomers was obtained with excellent regio- and enantioselectivity under mild conditions. Moreover, density functional theory (DFT) calculations provided insights into the nickel-catalyzed reaction mechanism and enantioselectivity control.

5.
J Cell Physiol ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38646844

ABSTRACT

The inhibition of cell surface crystal adhesion and an appropriate increase in crystal endocytosis contribute to the inhibition of kidney stone formation. In this study, we investigated the effects of different degrees of carboxymethylation on these processes. An injury model was established by treating human renal proximal tubular epithelial (HK-2) cells with 98.3 ± 8.1 nm calcium oxalate dihydrate (nanoCOD) crystals. The HK-2 cells were protected with carboxy (-COOH) Desmodium styracifolium polysaccharides at 1.17% (DSP0), 7.45% (CDSP1), 12.2% (CDSP2), and 17.7% (CDSP3). Changes in biochemical indexes and effects on nanoCOD adhesion and endocytosis were detected. The protection of HK-2 cells from nanoCOD-induced oxidative damage by carboxymethylated Desmodium styracifolium polysaccharides (CDSPs) is closely related to the protection of subcellular organelles, such as mitochondria. CDSPs can reduce crystal adhesion on the cell surface and maintain appropriate crystal endocytosis, thereby reducing the risk of kidney stone formation. CDSP2 with moderate -COOH content showed the strongest protective activity among the CDSPs.

6.
Turk J Gastroenterol ; 35(1): 48-60, 2024 01.
Article in English | MEDLINE | ID: mdl-38454277

ABSTRACT

BACKGROUND/AIMS: Pancreatic ductal adenocarcinoma is the tumor type with the highest incidence of perineural invasion. This study tries to identify the differentially expressed genes regulated between pancreatic ductal adenocarcinoma tissues with perineural invasion and without perineural invasion. MATERIALS AND METHODS: The GSE102238 profile was downloaded. Gene function and pathway analysis were subsequently conducted. A protein-protein interaction network was constructed to search for hub genes. Both univariate Cox analysis and multivariate Cox analysis were calculated to identify prognostic factors. Quantitative real-time polymerase chain reaction (RT-PCR) and overall survival analysis of hub genes were used to verify. RESULTS: Our study identified 242 differentially expressed genes including 68 upregulated differentially expressed genes and 174 downregulated differentially expressed genes, which were involved in important functions and pathways. Nine relevant core genes using protein-protein interaction analysis as well as nestin (NES)/vascular endothlial growth factor (VEGF) signaling pathway which is highly related to the pathological process of perineural invasion in pancreatic ductal adenocarcinoma were also discovered. The differentiation was identified as an independent prognostic factor (P < .05) after multivariate Cox analysis. Three upregulated genes (JUP, CALM1, and NES) and 6 downregulated genes (EPHA2, ARF1, ORM2, TERT, IL18, and CXCL3) were validated by quantitative RT-PCR and they all had markedly worse overall survival (P < .05). CONCLUSION: This analysis showed that 9 core genes including JUP, CALM1, NES, EPHA2, ARF1, ORM2, TERT, IL18, and CXCL3, as well as NES/VEGF signaling pathway, have a relationship with the development process of perineural invasion in pancreatic ductal adenocarcinoma. Cox analysis and overall survival analysis suggested differentiation as an independent prognostic factor and key roles for these 9 hub genes in perineural invasion prognosis in pancreatic ductal adenocarcinoma.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Interleukin-18/genetics , Vascular Endothelial Growth Factor A/genetics , Biomarkers, Tumor/genetics , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Prognosis , Proto-Oncogenes , Gene Expression
7.
Heliyon ; 10(2): e24666, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38298696

ABSTRACT

Rationale and objectives: The primary aim of this study was to conduct a retrospective comparative analysis of the survival outcomes in patients with recurrent cervical cancer (CC). Specifically, we aimed to compare the efficacy of chemotherapy alone versus the combined approach of chemotherapy and 125I brachytherapy subsequent to the failure of initial chemotherapy treatment. Materials and methods: Patients diagnosed with recurrent CC subsequent to the failure of initial chemotherapy from January 2007 to December 2016 were enrolled from 2 hospitals. These patients were then divided into two groups: Group A, which underwent second-line chemotherapy alone, and Group B, which received both second-line chemotherapy and 125I brachytherapy. The assessment of overall survival (OS) and progression-free survival (PFS) was carried out through propensity score matching (PSM) (1:1), Kaplan-Meier curves, log-rank tests, and Cox proportional hazard regression for survival analysis. Results: A matched cohort comprising 88 patients each in Group A and Group B was included in the study. In Group A, the 1-, 2-, and 3-year cumulative PFS rates were 40.9 %, 15.9 %, and 5.7 % respectively, while in Group B, these rates were significantly higher at 79.5 %, 48.9 %, and 25.0 % (P = 0.003). Similarly, the 1-, 2-, and 3-year cumulative OS rates among Group A were 67.0 %, 27.3 %, and 5.7 % compared to 89.8 %, 63.6 %, and 30.7 % among Group B, suggesting a difference with statistical significance (P < 0.001) between the two groups. Moreover, the incidence of complications was similar between groups (P = 0.698). Conclusions: Our findings suggest that the combined approach of chemotherapy and 125I brachytherapy yields superior therapeutic effects but similar complication rates compared to chemotherapy alone in patients experiencing local recurrence of CC following failed initial chemotherapy.

8.
Cell Signal ; 116: 111046, 2024 04.
Article in English | MEDLINE | ID: mdl-38242266

ABSTRACT

The incidence rate and mortality rate of cardiovascular disease rank first in the world. It is associated with various high-risk factors, and there is no single cause. Epigenetic modifications, such as DNA methylation or histone modification, actively participate in the initiation and development of cardiovascular diseases. Histone lysine methylation is a type of histone post-translational modification. The human Jumonji C domain (JMJD) protein family consists of more than 30 members. JMJD proteins participate in many key nuclear processes and play a key role in the specific regulation of gene expression, DNA damage and repair, and DNA replication. Importantly, increasing evidence shows that JMJD proteins are abnormally expressed in cardiovascular diseases, which may be a potential mechanism for the occurrence and development of these diseases. Here, we discuss the key roles of JMJD proteins in various common cardiovascular diseases. This includes histone lysine demethylase, which has been studied in depth, and less-studied JMJD members. Furthermore, we focus on the epigenetic changes induced by each JMJD member, summarize recent research progress, and evaluate their relationship with cardiovascular diseases and therapeutic potential.


Subject(s)
Cardiovascular Diseases , Humans , Histone Demethylases , Histones , Cognition , DNA Damage
9.
Angew Chem Int Ed Engl ; 63(8): e202319289, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38185722

ABSTRACT

Inherent chirality is used to describe chiral cyclic molecules devoid of central, axial, planar, or helical chirality and has tremendous applications in chiral recognition and enantioselective synthesis. Catalytic and divergent syntheses of inherently chiral molecules have attracted increasing interest from chemists. Herein, we report the enantioselective synthesis of inherently chiral tribenzocycloheptene derivatives via chiral phosphoric acid (CPA)-catalyzed condensation of cyclic ketones and hydroxylamines. This chemistry paves the way to accessing the less stable derivatives of 7-membered rings with inherent chirality. A series of chiral tribenzocycloheptene oxime ethers was synthesized in good yields (up to 97 %) with excellent enantioselectivities (up to 99 % ee).

10.
Nat Mater ; 23(2): 224-229, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38177379

ABSTRACT

Moiré excitons are emergent optical excitations in two-dimensional semiconductors with moiré superlattice potentials. Although these excitations have been observed on several platforms, a system with dynamically tunable moiré potential to tailor their properties is yet to be realized. Here we present a continuously tunable moiré potential in monolayer WSe2, enabled by its proximity to twisted bilayer graphene (TBG) near the magic angle. By tuning local charge density via gating, TBG provides a spatially varying and dynamically tunable dielectric superlattice for modulation of monolayer WSe2 exciton wave functions. We observed emergent moiré exciton Rydberg branches with increased energy splitting following doping of TBG due to exciton wave function hybridization between bright and dark Rydberg states. In addition, emergent Rydberg states can probe strongly correlated states in TBG at the magic angle. Our study provides a new platform for engineering moiré excitons and optical accessibility to electronic states with small correlation gaps in TBG.

12.
Acad Radiol ; 31(3): 833-843, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37487879

ABSTRACT

RATIONALE AND OBJECTIVES: The effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) or transarterial chemoembolization (TACE) for cases with single pseudo-capsuled hepatocellular carcinoma (pHCC), as well as their survival outcomes, were investigated. MATERIALS AND METHODS: A total of 196 cases with single pHCC (diameter >5 cm) receiving initial HAIC (n = 92) and TACE (n = 104) were enrolled. The propensity score match (PSM) approach based on Cox models was employed to tune any possible imbalance in treatment assignment. The overall survival (OS), objective response rate (ORR), progression-free survival (PFS), and partial response rate (PRR) of the subjects were investigated using the log-rank test. The independent risk factors for outcomes were investigated by univariate and multivariate analyses, and the results were analyzed using the Cox regression model. RESULTS: The median follow-up of the subjects was 22.3 months. After PSM, no significant difference was found in the OS of the HAIC and TACE groups (OS, 12.0 vs. 16.8 months; P = .267), while the median PFS of the TACE group was prolonged compared with the HAIC group (PFS, 5.7 vs. 2.8 months; P = .003). Moreover, PRR and ORR of the TACE group were prolonged compared with the HAIC group (PRR, 34.6% vs. 21.7%; P = .046; ORR, 35.6% vs. 21.7%; P = .033). The nomogram model showed high predictive accuracy and significant discrimination. CONCLUSION: TACE therapy could delay tumor progression compared with HAIC for cases with a single pHCC.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/therapy , Liver Neoplasms/drug therapy , Chemoembolization, Therapeutic/methods , Treatment Outcome , Hepatic Artery/diagnostic imaging , Retrospective Studies
13.
Nat Mater ; 23(1): 65-70, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37563291

ABSTRACT

Moiré superlattices host a rich variety of correlated electronic phases. However, the moiré potential is fixed by interlayer coupling, and it is dependent on the nature of carriers and valleys. In contrast, it has been predicted that twisted hexagonal boron nitride (hBN) layers can impose a periodic electrostatic potential capable of engineering the properties of adjacent functional layers. Here, we show that this potential is described by a theory of electric polarization originating from the interfacial charge redistribution, validated by its dependence on supercell sizes and distance from the twisted interfaces. This enables controllability of the potential depth and profile by controlling the twist angles between the two interfaces. Employing this approach, we further demonstrate how the electrostatic potential from a twisted hBN substrate impedes exciton diffusion in semiconductor monolayers, suggesting opportunities for engineering the properties of adjacent functional layers using the surface potential of a twisted hBN substrate.

14.
J Laparoendosc Adv Surg Tech A ; 34(2): 182-188, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37902957

ABSTRACT

Purpose: To investigate the use of ureteroscope-assisted laparoscopic surgery (UALS) in treating symptomatic prostatic utricle (PU) in children. Materials and Methods: Data on surgically treated cases of PU at the Department of Urology in Hunan Children's Hospital between September 2014 and September 2022 were retrospectively collected and analyzed. The diagnosis was confirmed by cystourethroscopy followed by ureteroscopy, and PU was excised by ureteroscope-assisted laparoscopy. Results: A total of 21 patients with PU were enrolled in this study. The median age of the patients at surgery was 8.1 (4.6-11.5) years. Karyotyping was available for 15 children: 13 (86.7%) were 46XY, 1 (6.7%) was 45X/46XY, and 1 (6.7%) was 45X/46XY/47XYY. The median length of the PU was 5.0 (4.1-7.1) cm. Nineteen patients underwent only ureteroscope-assisted laparoscopic excision, whereas 2 also had a perineal incision. All excisions were successfully performed. The median intraoperative blood loss was 25.0 (20.0-37.5) mL. The median hospital stay and follow-up durations were 18.0 (14.5-25.0) days and 24.0 (13.5-49.0) months, respectively. The patients reported no postoperative clinical symptoms. Conclusion: UALS allows for accurate patient positioning and thorough exposure of the anatomical structures, and it is a safe, effective, and minimally invasive treatment for PU in children.


Subject(s)
Laparoscopy , Ureteroscopes , Male , Child , Humans , Retrospective Studies , Prostate/surgery , Saccule and Utricle , Treatment Outcome
15.
Talanta ; 269: 125453, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38006729

ABSTRACT

Hierarchically nanostructured binary transition metal oxide-based materials with high conductivity and catalytic activity are quite attractive for the electrochemical quantitative detection of environmental pollutants due to their natural abundance, variable oxidation state, and excellent synergies between metal sites. Herein, a new hierarchical MnO-Fe3O4@C/expanded graphite (EG) composite is designed and synthesized through a simple and in situ annealing method with the utilization of bimetallic organic framework (FeMn-MOF)/EG precursor. The synthesized MnO-Fe3O4@C/EG composite possesses a unique hierarchical nanoarchitecture that small-sized bimetallic oxide nanoparticles of 10-40 nm completely encapsulated by amorphous carbon layers of 2-4 nm are uniformly distributed on the EG platform. This distinctive structure combines the advantages of high conductivity, excellent catalytic activity, and strong stability. Resultantly, when it is applied to monitor environmental endocrine disruptors, the sensor exhibits a significant catalytic effect on the electrochemical oxidation of bisphenol A (BPA), inducing an amplified response current. In addition, the sensor shows a wide linear range of 1-50 µM and 50-400 µM for the BPA monitor, giving a sensitivity of 5208.8 and 1641.9 µA mM-1 cm-2, respectively. This study offers a new approach to design hierarchical binary metal oxide-based sensing materials as well as to explore their electrochemical properties and applications for the determination of emerging contaminants.

16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1016460

ABSTRACT

ObjectiveTo investigate the antiviral effect of Menispermi Rhizoma total alkaloids and its relationship with the type Ⅰ interferon (IFN-Ⅰ) signaling pathway. MethodThe effects of Menispermi Rhizoma total alkaloids on the intracellular replication of influenza A virus (H1N1), vesicular stomatitis virus (VSV), and cerebral myocarditis virus (EMCV) were detected by fluorescent inverted microscope, flow cytometry, Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and Western blot. A mouse model infected with H1N1 was constructed, and the mice were divided into a control group, H1N1 model group, Menispermi Rhizoma total alkaloids groups (10, 20, 30 mg·kg-1), and oseltamivir group (40 mg·kg-1), so as to study the effects on the weight and survival rate of infected mice. Real-time PCR was used to detect the activation effect of Menispermi Rhizoma total alkaloids on the IFN-Ⅰ pathway in cells, and the relationship between the antiviral effect of Menispermi Rhizoma total alkaloids in IFNAR1 knockout A549 cells (IFNAR1-/--A549) and IFN-Ⅰ pathway was detected. ResultCompared with the control group, the virus proliferated significantly in the model group (P<0.01). Compared with the model group, Menispermi Rhizoma total alkaloids could significantly inhibit the replication of H1N1, VSV, and EMCV in vitro (P<0.01), inhibit the weight loss of the mice infected with the H1N1 in vivo, and improve the survival rate of mice (P<0.05). In addition, Menispermi Rhizoma total alkaloids activated the IFN-I pathway and relied on this pathway to exert the function of antiviral infection. ConclusionMenispermi Rhizoma total alkaloids exert antiviral effects in vivo and in vitro by activating the IFN-Ⅰ pathway.

17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1016364

ABSTRACT

@#Objective To evaluate the short-term results of sleeve wrapping technique using remnant aortic wall in modified Bentall procedure. Methods The patients undergoing modified Bentall procedure with the remnant aortic wall as a sleeve to cover the sewing area of composite valved graft and the aortic annulus for proximal hemostasis between March 2021 and March 2022 in Shenzhen Fuwai Hospital were enrolled. Short-term results were assessed by cardiopulmonary bypass time, aortic clamping time, mechanical ventilation time, ICU stay, postoperative hospital stay, effusion drainage on the first postoperative day, left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), and follow-up results. Results A total of 14 patients were collected, including 12 males and 2 females, with a mean age of 55.33±10.57 years. There was no postoperative or follow-up death. Cardiopulmonary bypass time was 147.90±21.29 min, aortic clamping time was 115.70±15.23 min, mechanical ventilation time was 19.42±8.98 h, ICU stay was 99.08±49.42 h, and postoperative hospital stay was 16.33±2.74 d. Thoracic drainage volume was 333.33±91.98 mL on the first postoperative day. Only 2 patients required blood transfusion (4.5 U and 2 U, respectively). During the follow-up of 6.17±3.69 months, there was no death, no aortic or valve-related complications. There was statistical difference in the LVEDD between preoperation and before discharge after surgery (P<0.001), and between half a year after surgery and before discharge after surgery (P<0.001). There was a little decrease of LVEF before discharge after surgery compared with preoperative LVEF, but there was no statistical difference (P=0.219). There was no statistical difference in the LVEF half a year after operation compared with that before operation (P=1.000). Conclusion Sleeve wrapping technique using remnant aortic wall in modified Bentall procedure has good short-term results. This modification may be a simple, effective way in controlling proximal bleeding.

18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1009356

ABSTRACT

OBJECTIVE@#To analyze the clinical data and genetic characteristics of a child with CLN1 neuronal ceroid lipofuscinosis in conjunct with Hereditary hyperferritinemia cataract syndrome (HHCS).@*METHODS@#A child who was admitted to the PICU of the First Affiliated Hospital of Zhengzhou University in November 2020 was selected as the study subject. Clinical data of the child was collected. Genetic testing was carried out for the child, and the result was analyzed in the light of literature review to explore the clinical and genetic characteristics to facilitate early identification.@*RESULTS@#The patient, a 3-year-old male, had mainly presented with visual impairment, progressive cognitive and motor regression, and epilepsy. Cranial magnetic resonance imaging revealed deepened sulci in bilateral cerebral hemispheres, and delayed myelination. The activity of palmitoyl protein thioesterase was low (8.4 nmol/g/min, reference range: 132.2 ~ 301.4 nmol/g/min), whilst serum ferritin was increased (2417.70 ng/mL, reference range: 30 ~ 400 ng/ml). Fundoscopy has revealed retinal pigment degeneration. Whole exome sequencing revealed that he has harbored c.280A>C and c.124-124+3delG compound heterozygous variants of the PPT1 gene, which were respectively inherited from his father and mother. Neither variant has been reported previously. The child has also harbored a heterozygous c.-160A>G variant of the FTL gene, which was inherited from his father. Based on the clinical phenotype and results of genetic testing, the child was diagnosed as CLN1 and HHCS.@*CONCLUSION@#The compound heterozygous variants of the PPT1 gene probably underlay the disorders in this child. For children with CLN1 and rapidly progressing visual impairment, ophthalmological examination should be recommended, and detailed family history should be taken For those suspected for HHCS, genetic testing should be performed to confirm the diagnosis.


Subject(s)
Child, Preschool , Humans , Male , Cataract/genetics , Genetic Testing , Mutation , Neuronal Ceroid-Lipofuscinoses/pathology , Vision Disorders/genetics
19.
Small ; 20(22): e2307961, 2024 May.
Article in English | MEDLINE | ID: mdl-38126911

ABSTRACT

Activating the stimulator of the interferon gene (STING) is a promising immunotherapeutic strategy for converting "cold" tumor microenvironment into "hot" one to achieve better immunotherapy for malignant tumors. Herein, a manganese-based nanotransformer is presented, consisting of manganese carbonyl and cyanine dye, for MRI/NIR-II dual-modality imaging-guided multifunctional carbon monoxide (CO) gas treatment and photothermal therapy, along with triggering cGAS-STING immune pathway against triple-negative breast cancer. This nanosystem is able to transfer its amorphous morphology into a crystallographic-like formation in response to the tumor microenvironment, achieved by breaking metal-carbon bonds and forming coordination bonds, which enhances the sensitivity of magnetic resonance imaging. Moreover, the generated CO and photothermal effect under irradiation of this nanotransformer induce immunogenic death of tumor cells and release damage-associated molecular patterns. Simultaneously, the Mn acts as an immunoactivator, potentially stimulating the cGAS-STING pathway to augment adaptive immunity, resulting in promoting the secretion of type I interferon, the proliferation of cytotoxic T lymphocytes and M2-macrophages repolarization. This nanosystem-based gas-photothermal treatment and immunoactivating therapy synergistic effect exhibit excellent antitumor efficacy both in vitro and in vivo, reducing the risk of triple-negative breast cancer recurrence and metastasis; thus, this strategy presents great potential as multifunctional immunotherapeutic agents for cancer treatment.


Subject(s)
Immunotherapy , Manganese , Photothermal Therapy , Triple Negative Breast Neoplasms , Triple Negative Breast Neoplasms/therapy , Immunotherapy/methods , Manganese/chemistry , Humans , Animals , Photothermal Therapy/methods , Cell Line, Tumor , Female , Magnetic Resonance Imaging/methods , Mice , Tumor Microenvironment , Nanoparticles/chemistry , Phototherapy/methods
20.
Article in English | MEDLINE | ID: mdl-38082696

ABSTRACT

As is well known, cognitive performances are highly influenced by cognitive load, so it is meaningful to find some ways to effectively reduce the cognitive load. In particular, aerobic exercise is a promising way. However, the neural evidence is still lacking in understanding how aerobic exercise minimizes cognitive load. To solve the problem, this study adopted the N-back task in both the before (BE) and after (AE) aerobic exercise periods, behavioral and EEG data were recorded from 21 participants. Functional connectivity was constructed by the weighted phase lag index (WPLI), and effective connectivity was constructed by the partially directed coherent (PDC). Consequently, by comparing the connection strength and pattern of BE and AE, it is found that in low-frequency (0~8 Hz), aerobic exercise could enhance the connection strength of WPLI networks under high cognitive load, and increase the importance of the forehead region in the communication of PDC networks under low cognitive load. These results could advance our understanding of the underlying mechanisms of how aerobic exercise modulates cognitive load.


Subject(s)
Exercise Therapy , Exercise , Humans , Frontal Lobe , Cognition
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