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1.
Small Methods ; : e2400097, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38703024

ABSTRACT

Calcium-ion batteries (CIBs) are considered as potential next-generation energy storage systems due to their abundant reserves and relatively low cost. However, irreversible structural changes and weak conductivity still hinder in current CIBs cathode materials. Herein, an organic molecular intercalation strategy is proposed, in which V2O5 regulated with quinoline, pyridine, and water molecules are studied as cathode material to provide fast ion diffusion channels, large storage host, and high conductivity for Ca ions. Among them, V2O5-quinoline (QVO) owns the largest interplanar spacing of 1.25 nm and the V-O chains are connected with organic molecular by hydrogen bond, which stabilizes the crystal structure. As a result, QVO exhibits a specific capacity of 168 mAh g-1 at 1 A g-1 and capacity retention of 80% after 500 cycles at 5 A g-1 than the other materials. Furthermore, X-Ray diffraction and X-ray absorption spectroscopy results reveal a reversible order-disorder transformation mechanism of Ca2+ for QVO, which can make full use of the abundant active sites for high capacity and simultaneously achieve fast reaction kinetics for excellent rate performance. These results demonstrate that QVO is a promising cathode material for CIBs, providing more choices for the development of high-performance CIBs.

2.
Am J Transl Res ; 16(4): 1219-1227, 2024.
Article in English | MEDLINE | ID: mdl-38715832

ABSTRACT

OBJECTIVE: We aimed to assess the impact of integrated nursing and psychological intervention on pain intensity and patient satisfaction in individuals with urinary calculi. METHODS: This retrospective study included 94 urological patients from the Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, between January 2020 and June 2022. Participants were divided into a control group (n=48), receiving routine nursing and psychological intervention, and a study group (n=46), receiving integrated nursing and psychological intervention. We compared pain intensity, pain relief rate, patient satisfaction, Numeric Rating Scale (NRS) score, Pittsburgh Sleep Quality Index (PSQI) score, Self-rating Depression Scale (SDS) score, Self-rating Anxiety Scale (SAS) score, and quality of life scores between the groups. RESULTS: The study group had shorter hospital stays and lower hospitalization costs than the control group (both P < 0.05). Pain relief and satisfaction rates were higher in the study group (both P < 0.05). Post-intervention, both groups showed significant reductions in NRS, PSQI, SDS, and SAS scores, with greater reductions in the study group (all P < 0.05). Quality of life scores increased in both groups, more so in the SG (P < 0.05). The study group also had fewer adverse events (P < 0.05). Both groups showed decreased serum creatinine and blood urea nitrogen levels post-intervention, with a more significant decline in the study group (P < 0.05). Education, marital status, and occupation were major factors influencing outcomes in urinary calculi patients. CONCLUSION: Integrated nursing and psychological intervention significantly alleviates pain, improves emotional well-being, enhances sleep quality, increases overall life quality, and contributes to high patient satisfaction among urinary calculi patients.

3.
Am J Case Rep ; 25: e943174, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38704637

ABSTRACT

BACKGROUND Simultaneous bilateral basal ganglia hemorrhage is an infrequent occurrence in medical literature. The etiology of bilateral basal ganglia intracerebral hemorrhage remains elusive, in contrast to that of unilateral basal ganglia hypertensive intracerebral hemorrhage, resulting in lack of consensus among scholars. Importantly, patients with uremia and cerebral hemorrhage, especially patients with large hematoma volumes, exhibit a markedly elevated mortality rate. Patients can benefit from implementation of positive and efficacious therapeutic approaches. CASE REPORT We present a clinical case involving a 42-year-old male patient who was admitted to the hospital in a comatose state. The initial head computed tomography scan revealed the presence of simultaneous basal ganglia hemorrhage; this phenomenon could potentially be attributed to the occurrence of cerebral hemorrhage induced by severe renal hypertension in individuals with uremia. The patient underwent emergency surgical intervention to evacuate the hematoma, followed by continuous blood purification treatment. Ultimately, these interventions have the potential to improve patient outcomes. CONCLUSIONS Incidence of bilateral basal ganglia hemorrhage is exceptionally rare and associated with an unfavorable prognosis, often resulting in mortality among individuals with severe underlying conditions or complications. The hematoma was successfully eliminated through the use of skull resection and neuroendoscopy techniques, resulting in favorable outcomes. The implementation of bedside continuous hemodialysis in patients with uremic cerebral hemorrhage can enhance therapeutic efficacy, thus warranting its recommendation for similar cases. Based on our observations, it is plausible that severe hypertension plays a contributory role in the development of simultaneous bilateral basal ganglia bleeding.


Subject(s)
Basal Ganglia Hemorrhage , Humans , Male , Adult , Basal Ganglia Hemorrhage/complications , Tomography, X-Ray Computed
4.
J Photochem Photobiol B ; 256: 112940, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38776590

ABSTRACT

Photobiomodulation (PBM) is a well-established medical technology that employs diverse light sources like lasers or light-emitting diodes to generate diverse photochemical and photophysical reactions in cells, thereby producing beneficial clinical outcomes. In this study, we introduced an 830 nm near-infrared (NIR) laser irradiation system combined with a microscope objective to precisely and controllably investigate the impact of PBM on the migration and viability of human adipose mesenchymal stem cells (hADSCs). We observed a biphasic dose-response in hADSCs' viability and migration after PBM exposure (0-10 J/cm2), with the 5 J/cm2 group showing significantly higher cell viability and migration ability than other groups. Additionally, at the optimal dose of 5 J/cm2, we used nanoparticle tracking analysis (NTA) and found a 6.25-fold increase in the concentration of extracellular vesicles (EVs) derived from hADSCs (PBM/ADSC-EVs) compared to untreated cells (ADSC-EVs). Both PBM/ADSC-EVs and ADSC-EVs remained the same size, with an average diameter of 56 nm measured by the ExoView R200 system, which falls within the typical size range for exosomes. These findings demonstrate that PBM not only improves the viability and migration of hADSCs but also significantly increases the EV yield.

5.
Braz J Cardiovasc Surg ; 39(3): e20230160, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38629955

ABSTRACT

OBJECTIVE: To evaluate the occurrence of aortic dilatation and its associated predictors with coarctation of the aorta (CoA) in infants using multi-slice computed tomography (MSCT). METHODS: The clinical data of 47 infantile patients with CoA diagnosed by MSCT and 28 infantile patients with simple ventricular septal defect were analyzed retrospectively. Aortic diameters were measured at six different levels, and aortic sizes were compared by z score. The coarctation site-diaphragm ratio was used to describe the degree of narrowing. Relevant clinical data were collated and analyzed. RESULTS: The dilation rate and z score of the ascending aorta in the severe CoA group were significantly higher than those in the mild CoA group (11 [52.38%] vs. 21 [80.77%], P=0.038 and 2.00 ± 0.48 vs. 2.36 ± 0.43, P=0.010). Pearson's correlation analysis found that the z score of the ascending aorta was negatively correlated with the coarctation site-diaphragm ratio value (r=-0.410, P=0.004). A logistic retrospective analysis found that an increased degree of coarctation was an independent predictor of aortic dilatation (adjusted odds ratio 0.002; 95% confidence interval 0.00-0.819; P=0.043). The z score of the ascending aorta in the severe CoA group was significantly higher than that in the ventricular septal defect group (P<0.05). CONCLUSION: Most infants with CoA can also have significant dilatation of the ascending aorta, and the degree of this dilatation is related to the degree of coarctation. Assessment of aortic diameter and related malformations by MSCT can predict the risk of aortic dilatation in infants with CoA.


Subject(s)
Aortic Coarctation , Heart Septal Defects, Ventricular , Infant , Humans , Computed Tomography Angiography , Dilatation , Retrospective Studies , Aortic Coarctation/diagnostic imaging
6.
J Chem Phys ; 160(16)2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38647312

ABSTRACT

Understanding and further regulating the degradation of mandrel materials is a key aspect of target fabrication in inertial confinement fusion (ICF). Here, a quasi-one-dimensional confinement model is developed using a series of single-walled carbon nanotubes with varying diameters (Dm), and the degradation of poly-α-methylstyrene (PAMS) as a typical mandrel material is investigated under such confined conditions by using the combined method of quantum mechanics and molecular mechanics. In comparison to the isolated system, the calculations show that confinement can decrease or increase the energy barriers of PAMS degradation, which directly depends on Dm. Following which a clear exponential relationship between the degradation rate of PAMS and its own density is derived, indicating that the density of PAMS can be used to regulate mandrel degradation. This work highlights the important effects of confinement on degradation and provides a valuable reference for further development of polymer degradation technologies in ICF target fabrication and other fields.

7.
J Org Chem ; 89(9): 6607-6614, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38624206

ABSTRACT

The trivalent phosphine-catalyzed [4+1] spiro-annulation reaction of allenyl imide and activated methylene cyclocompounds has been developed for the construction of various spiro-2-cyclopenten-1-ones. Oxindoles, 3-isochromanones, and 2-indanones are selected as 1C synthons to capture the in situ-generated bis-electrophilic α,ß-unsaturated ketenyl phosphonium intermediate, affording the corresponding monospiro- and bispiro-cyclopentenones in good to excellent yields (≤91%) under mild conditions. The primary attempt at asymmetric catalysis using monophosphine (R)-SITCP provides promising enantioselectivity (45% ee). A plausible reaction mechanism is also proposed.

8.
Surg Endosc ; 38(5): 2857-2870, 2024 May.
Article in English | MEDLINE | ID: mdl-38575828

ABSTRACT

INTRODUCTION: A survival paradox between T4N0 (Stage IIB/IIC) and Stage IIIA colon cancer exists, even after adjusting for adequate lymph node (LN) retrieval and receipt of adjuvant chemotherapy (C). We conducted a large hospital-based study to re-evaluate this survival paradox based on the newest 8th edition staging system. METHODS: The National Cancer Data Base was queried to evaluate 35,606 patients diagnosed with Stage IIB, IIC, and IIIA colon cancer between 2010 and 2017. The Kaplan-Meier method and log-rank test were used to compare unadjusted overall survival (OS). Multivariable Cox proportional hazards model was used to determine the association of stage with hazard ratios adjusted for relevant demographic and clinical variables including ≥ 12 LNs retrieved and receipt of adjuvant chemotherapy. P value < 0.05 was considered statistically significant. RESULTS: The 5-year OS for optimally treated stage IIIA colon cancer (receipt of C) was 84.3%, which was significantly higher than stage IIB/C (≥ 12 LNs retrieved + C) (72.8%; P < 0.0001). Stage was an independent predictor of OS. Among optimally treated Stage IIIA patients, T1N1 had the best survival (90.6%) while stage T4bN0 (stage IIC) had the worst (70.9%) (P < 0.0001). Compared to stage IIB, stage IIC had a 17% increased risk of overall death while stage IIIA had a 21% reduction in death (P < 0.0001). CONCLUSION: Stage IIB/C and Stage IIIA survival paradox persists even after accounting for receipt of adjuvant chemotherapy and adequate lymph node retrieval. Future iteration of the TNM system should take this paradox into consideration.


Subject(s)
Colonic Neoplasms , Neoplasm Staging , Humans , Colonic Neoplasms/pathology , Colonic Neoplasms/mortality , Colonic Neoplasms/therapy , Female , Male , Aged , Middle Aged , Chemotherapy, Adjuvant , United States/epidemiology , Retrospective Studies , Survival Rate , Colectomy , Aged, 80 and over , Lymph Node Excision , Kaplan-Meier Estimate
9.
Seizure ; 116: 87-92, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38523034

ABSTRACT

OBJECTIVES: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy. METHODS: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations. RESULTS: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation. SIGNIFICANCE: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity.


Subject(s)
Epilepsy , Intellectual Disability , Malformations of Cortical Development , Neurodevelopmental Disorders , Humans , Intellectual Disability/genetics , Epilepsy/genetics , Neurodevelopmental Disorders/genetics , Mutation, Missense , Phenotype , Cytoskeletal Proteins/genetics
10.
J Med Genet ; 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38508705

ABSTRACT

BACKGROUND: The ZFHX3 gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between ZFHX3 variants and epilepsy. METHODS: Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A Drosophila Zfh2 knockdown model was used to validate the association between ZFHX3 and epilepsy. RESULTS: Compound heterozygous ZFHX3 variants were identified in eight unrelated cases. The burden of ZFHX3 variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In Zfh2 knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The Zfh2 knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that ZFHX3 orthologous were highly expressed in the embryonic stage and decreased dramatically after birth. CONCLUSION: ZFHX3 is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness.

11.
Cancer Res ; 84(11): 1817-1833, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38484085

ABSTRACT

Immune checkpoint inhibitors have limited efficacy in hepatocellular carcinoma (HCC). Macrophages are the most abundant immune cells in HCC, suggesting that a better understanding of the intrinsic processes by which tumor cells regulate macrophages could help identify strategies to improve response to immunotherapy. As signaling lymphocytic activation molecule (SLAM) family members regulate various immune functions, we investigated the role of specific SLAM receptors in the immunobiology of HCC. Comparison of the transcriptomic landscapes of immunotherapy-responsive and nonresponsive patients with advanced HCC identified SLAMF7 upregulation in immunotherapy-responsive HCC, and patients with HCC who responded to immunotherapy also displayed higher serum levels of SLAMF7. Loss of Slamf7 in liver-specific knockout mice led to increased hepatocarcinogenesis and metastasis, elevated immunosuppressive macrophage infiltration, and upregulated PD-1 expression in CD8+ T cells. HCC cell-intrinsic SLAMF7 suppressed MAPK/ATF2-mediated CCL2 expression to regulate macrophage migration and polarization in vitro. Mechanistically, SLAMF7 associated with SH2 domain-containing adaptor protein B (SHB) through its cytoplasmic 304 tyrosine site to facilitate the recruitment of SHIP1 to SLAMF7 and inhibit the ubiquitination of TRAF6, thereby attenuating MAPK pathway activation and CCL2 transcription. Pharmacological antagonism of the CCL2/CCR2 axis potentiated the therapeutic effect of anti-PD-1 antibody in orthotopic HCC mouse models with low SLAMF7 expression. In conclusion, this study highlights SLAMF7 as a regulator of macrophage function and a potential predictive biomarker of immunotherapy response in HCC. Strategies targeting CCL2 signaling to induce macrophage repolarization in HCC with low SLAMF7 might enhance the efficacy of immunotherapy. SIGNIFICANCE: CCL2 upregulation caused by SLAMF7 deficiency in hepatocellular carcinoma cells induces immunosuppressive macrophage polarization and confers resistance to immune checkpoint blockade, providing potential biomarkers and targets to improve immunotherapy response in patients.


Subject(s)
Carcinoma, Hepatocellular , Chemokine CCL2 , Immunotherapy , Liver Neoplasms , Macrophages , Mice, Knockout , Signaling Lymphocytic Activation Molecule Family , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Liver Neoplasms/genetics , Animals , Signaling Lymphocytic Activation Molecule Family/metabolism , Signaling Lymphocytic Activation Molecule Family/genetics , Humans , Mice , Immunotherapy/methods , Chemokine CCL2/metabolism , Macrophages/immunology , Macrophages/metabolism , Signal Transduction , Mice, Inbred C57BL , Cell Line, Tumor
12.
Abdom Radiol (NY) ; 49(5): 1584-1592, 2024 05.
Article in English | MEDLINE | ID: mdl-38502213

ABSTRACT

PURPOSE: We sought to summarize the value of contrast-enhanced computed tomography (CECT) in the differential diagnosis of bladder paraganglioma (BPG) and bladder cancer. METHODS: The medical records of 19 patients with BPG (13 males, 6 females) and 56 patients with bladder cancer (49 males, 7 females) between November 2007 and June 2023 were retrospectively reviewed. All patients underwent unenhanced and contrast-enhanced CT scanning. RESULTS: Patient age (46.4 ± 11.1 years vs. 58.6 ± 16.0 years), tumor calcification (1/19 vs. 18/56), stalk (0/19 vs. 10/56), internal vessels (15/19 vs. 19/56) and the enlarged adjacent supplying artery (14/19 vs. 10/56) were significantly different between BPG and bladder cancer (P < 0.05). The CT value in the corticomedullary phase (92.4 ± 16.6 HU vs. 64.0 ± 14.5 HU) and the contrast-enhanced value in the corticomedullary phase (54.5 ± 17.4 HU vs. 28.5 ± 12.8 HU) were significantly greater in BPG patients than in bladder cancer patients (P < 0.001), with corresponding area under the curve values of 0.930 and 0.912, respectively. The optimal cutoff values were 83.2 HU and 38.5 HU, respectively. A CT value > 83.2 HU in the corticomedullary phase and a contrast-enhanced CT value > 38.5 HU in the corticomedullary phase were used to indicate BPG with sensitivities of 78.9% and 89.5%, respectively, and specificities of 94.6% and 75.0%, respectively. CONCLUSION: The corticomedullary phase of CECT plays an important role in the preoperative differential diagnosis of BPG and bladder cancer.


Subject(s)
Contrast Media , Paraganglioma , Tomography, X-Ray Computed , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/diagnostic imaging , Male , Female , Middle Aged , Diagnosis, Differential , Paraganglioma/diagnostic imaging , Retrospective Studies , Tomography, X-Ray Computed/methods , Adult , Aged , Urinary Bladder/diagnostic imaging
13.
Polymers (Basel) ; 16(5)2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38475284

ABSTRACT

Polyamide 66 was extensively utilized in various applications contributed by its excellent mechanical performance and outstanding durability. However, its high crystallinity renders it to have low transparency, which seriously limits its application in optical devices. Herein, a highly transparent polyamide (PA) 66-based copolymer was reported using 4,4'-diaminodicyclohexylmethane (PACM), adipic acid, and polyamide 66 salt as the reaction monomers. Wide-angle X-ray diffraction (WAXD) analysis revealed that the crystal phase of the synthesized PA66/PACM6 displayed a clear transition from α to γ as the PACM6 increased accompanied by a decreased intensity in the diffraction peak of the copolymer, whose transmittance was successfully adjusted reaching as high as 92.5% (at 550 nm) when the PACM6 was 40 wt%. Moreover, the copolymer with a higher content of PACM6 exhibited larger toughness. On the other hand, the biaxially oriented films of PA66/PACM6 (20 wt%) were also prepared, and it was found that the transparency of the PA66/PACM6 copolymer could be further enhanced via adjusting the stretching ratio of the film. Furthermore, the mechanical strength of the biaxially oriented PA66/PACM6 was also improved with the increase in the orientation degree in the stretching process, indicating that the physical properties of the transparent PA66 were significantly influenced by its alicyclic structure, and the introduction of PACM into PA66 was capable of effectively improving the optical and crystalline characteristics of PA66, revealing that the synthetic strategy has great potential for guiding the design and development of transparent polyamide materials.

14.
Am J Hypertens ; 2024 Mar 09.
Article in English | MEDLINE | ID: mdl-38459938

ABSTRACT

The effectiveness of Renal Denervation (RDN) in reducing blood pressure and systemic sympathetic activity in hypertensive patients has been established. However, the underlying central mechanism remains unknown. This study aimed to investigate the role of RDN in regulating cardiovascular function via the central Renin-Angiotensin System (RAS) pathway. Ten-week-old Spontaneously Hypertensive Rats (SHR) were subjected to Selective Afferent Renal Denervation (ADN) using capsaicin solution. We hypothesized that ADN would effectively reduce blood pressure and rebalance the RAS component of PVN in SHR. The experimental results show that ADN group exhibited significantly lower blood pressure, reduced systemic sympathetic activity, decreased chronic neuronal activation marker C-FOS expression in the paraventricular nucleus of hypothalamus (PVN), and improved arterial baroreflex function, compared with the Sham group. Furthermore, ACE and AT1 protein expression was reduced while ACE2 and MAS protein expression was increased in the PVN of SHR after ADN. These findings suggest that RDN may exert these beneficial effects through modulating the central RAS pathway.

15.
Cell Death Differ ; 31(4): 447-459, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38413797

ABSTRACT

Hypoxia is a hallmark of cancer development. However, the molecular mechanisms by which hypoxia promotes tumor metastasis are not fully understood. In this study, we demonstrate that hypoxia promotes breast cancer metastasis through suppression of ΔNp63α in a HIF1α-independent manner. We show that hypoxia-activated XBP1s forms a stable repressor protein complex with HDAC2 and EZH2 to suppress ΔNp63α transcription. Notably, H3K27ac is predominantly occupied on the ΔNp63 promoter under normoxia, while H3K27me3 on the promoter under hypoxia. We show that XBP1s binds to the ΔNp63 promoter to recruit HDAC2 and EZH2 in facilitating the switch of H3K27ac to H3K27me3. Pharmacological inhibition or the knockdown of either HDAC2 or EZH2 leads to increased H3K27ac, accompanied by the reduced H3K27me3 and restoration of ΔNp63α expression suppressed by hypoxia, resulting in inhibition of cell migration. Furthermore, the pharmacological inhibition of IRE1α, but not HIF1α, upregulates ΔNp63α expression in vitro and inhibits tumor metastasis in vivo. Clinical analyses reveal that reduced p63 expression is correlated with the elevated expression of XBP1, HDAC2, or EZH2, and is associated with poor overall survival in human breast cancer patients. Together, these results indicate that hypoxia-activated XBP1s modulates the epigenetic program in suppression of ΔNp63α to promote breast cancer metastasis independent of HIF1α and provides a molecular basis for targeting the XBP1s/HDAC2/EZH2-ΔNp63α axis as a putative strategy in the treatment of breast cancer metastasis.


Subject(s)
Breast Neoplasms , Enhancer of Zeste Homolog 2 Protein , Epigenesis, Genetic , Histone Deacetylase 2 , Hypoxia-Inducible Factor 1, alpha Subunit , Tumor Suppressor Proteins , X-Box Binding Protein 1 , Humans , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Enhancer of Zeste Homolog 2 Protein/metabolism , Enhancer of Zeste Homolog 2 Protein/genetics , X-Box Binding Protein 1/metabolism , X-Box Binding Protein 1/genetics , Histone Deacetylase 2/metabolism , Histone Deacetylase 2/genetics , Female , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Tumor Suppressor Proteins/metabolism , Tumor Suppressor Proteins/genetics , Animals , Cell Line, Tumor , Neoplasm Metastasis , Mice , Gene Expression Regulation, Neoplastic , Transcription Factors/metabolism , Transcription Factors/genetics , Cell Hypoxia/genetics
16.
Ann Surg Oncol ; 31(5): 2925-2931, 2024 May.
Article in English | MEDLINE | ID: mdl-38361092

ABSTRACT

INTRODUCTION: Medicaid expansion (ME) impacted patients when assessed at a national level. However, of the 32 states in which Medicaid expansion occurred, only 3 were Southern states. Whether results apply to Southern states that share similar geopolitical perspectives remains elusive. We aimed to assess the impact of ME on pancreatic ductal adenocarcinoma (PDAC) treatment in eight Southern states in the USA. PATIENTS AND METHODS: We identified uninsured or Medicaid patients (age 40-64 years) diagnosed with PDAC between 2011 and 2018 in Southern states from the North American Association of Central Cancer Registries-Cancer in North America (NAACCR-CiNA) research dataset. Medicaid-expanded states (MES; Louisiana, Kentucky, and Arkansas) were compared with non-MES (NMES; Tennessee, Alabama, Mississippi, Texas, and Oklahoma) using multivariate logistic regression. P < 0.05 was considered statistically significant. RESULTS: Among 3036 patients, MES significantly increased odds of Medicaid insurance by 36%, and increased proportions of insured Black patients by 3.7%, rural patients by 3.8%, and impoverished patients by 18.4%. After adjusting for age, race, rural-urban status, poverty status, and summary stage, the odds of receiving radiation therapy decreased by 26% for each year of expansion in expanded states (P = 0.01). Last, ME did not result in a significant difference between MES and NMES in diagnosing early stage disease (P = 0.98) nor in receipt of chemotherapy or surgery (P = 0.23 and P = 0.63, respectively). CONCLUSIONS: ME in Southern states increased insurance access to traditionally underserved groups. Interestingly, ME decreased the odds of receiving radiation therapy yearly and had no significant impact on receipt of chemotherapy or surgery.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , United States/epidemiology , Humans , Adult , Middle Aged , Medicaid , Patient Protection and Affordable Care Act , Insurance Coverage , Carcinoma, Pancreatic Ductal/epidemiology , Carcinoma, Pancreatic Ductal/therapy , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/therapy
17.
Biomolecules ; 14(2)2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38397459

ABSTRACT

Peripheral blood lymphocytes (PBLs), which play a pivotal role in orchestrating the immune system, garner minimal attention in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The impact of primary liver cancers on PBLs remains unexplored. In this study, flow cytometry facilitated the quantification of cell populations, while transcriptome of PBLs was executed utilizing 10× single-cell sequencing technology. Additionally, pertinent cases were curated from the GEO database. Subsequent bioinformatics and statistical analyses were conducted utilizing R (4.2.1) software. Elevated counts of NK cells and CD8+ T cells were observed in both ICC and HCC when compared to benign liver disease (BLD). In the multivariate Cox model, NK cells and CD8+ T cells emerged as independent risk factors for recurrence-free survival. Single-cell sequencing of PBLs uncovered the downregulation of TGFß signaling in tumor-derived CD8+ T cells. Pathway enrichment analysis, based on differential expression profiling, highlighted aberrations in selenium metabolism. Proteomic analysis of preoperative and postoperative peripheral blood samples from patients undergoing tumor resection revealed a significant upregulation of SELENBP1 and a significant downregulation of SEPP1. Primary liver cancer has a definite impact on PBLs, manifested by alterations in cellular quantities and selenoprotein metabolism.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Selenium , Humans , Carcinoma, Hepatocellular/metabolism , Selenium/metabolism , Proteomics , Liver Neoplasms/metabolism , CD8-Positive T-Lymphocytes , Killer Cells, Natural
18.
Poult Sci ; 103(3): 103376, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38228059

ABSTRACT

Wenchang chicken, a prized local breed in Hainan Province of China renowned for its exceptional adaptability to tropical environments and good meat quality, is deeply favored by the public. However, an insufficient understanding of its population architecture and the unclear genetic basis that governs its typical attributes have posed challenges in the protection and breeding of this precious breed. To address these gaps, we conducted whole-genome resequencing on 200 Wenchang chicken samples derived from 10 distinct strains, and we gathered data on an array of 21 phenotype traits. Population genomics analysis unveiled distinctive population structures in Wenchang chickens, primarily attributed to strong artificial selection for different feather colors. Selection sweep analysis identified a group of candidate genes, including PCDH9, DPF3, CDIN1, and SUGCT, closely linked to adaptations that enhance resilience in tropical island habitats. Genome-wide association studies (GWAS) highlighted potential candidate genes associated with diverse feather color traits, encompassing TYR, RAB38, TRPM1, GABARAPL2, CDH1, ZMIZ1, LYST, MC1R, and SASH1. Through the comprehensive analysis of high-quality genomic and phenotypic data across diverse Wenchang chicken resource groups, this study unveils the intricate genetic backgrounds and population structures of Wenchang chickens. Additionally, it identifies multiple candidate genes linked to environmental adaptation, feather color variations, and production traits. These insights not only provide genetic reference for the purification and breeding of Wenchang chickens but also broaden our understanding of the genetic basis of phenotypic diversity in chickens.


Subject(s)
Chickens , Genome-Wide Association Study , Animals , Chickens/genetics , Genome-Wide Association Study/veterinary , Genomics , Phenotype , Serogroup
19.
Seizure ; 116: 4-13, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37777370

ABSTRACT

PURPOSE: To provide an updated list of epilepsy-associated genes based on clinical-genetic evidence. METHODS: Epilepsy-associated genes were systematically searched and cross-checked from the OMIM, HGMD, and PubMed databases up to July 2023. To facilitate the reference for the epilepsy-associated genes that are potentially common in clinical practice, the epilepsy-associated genes were ranked by the mutation number in the HGMD database and by case number in the China Epilepsy Gene 1.0 project, which targeted common epilepsy. RESULTS: Based on the OMIM database, 1506 genes were identified to be associated with epilepsy and were classified into three categories according to their potential association with epilepsy or other abnormal phenotypes, including 168 epilepsy genes that were associated with epilepsies as pure or core symptoms, 364 genes that were associated with neurodevelopmental disorders as the main symptom and epilepsy, and 974 epilepsy-related genes that were associated with gross physical/systemic abnormalities accompanied by epilepsy/seizures. Among the epilepsy genes, 115 genes (68.5%) were associated with epileptic encephalopathy. After cross-checking with the HGMD and PubMed databases, an additional 1440 genes were listed as potential epilepsy-associated genes, of which 278 genes have been repeatedly identified variants in patients with epilepsy. The top 100 frequently reported/identified epilepsy-associated genes from the HGMD database and the China Epilepsy Gene 1.0 project were listed, among which 40 genes were identical in both sources. SIGNIFICANCE: Recognition of epilepsy-associated genes will facilitate genetic screening strategies and be helpful for precise molecular diagnosis and treatment of epilepsy in clinical practice.


Subject(s)
Epilepsy , Humans , Epilepsy/genetics , Seizures/genetics , Genetic Testing , Mutation/genetics , Databases, Factual , Phenotype
20.
J Phys Chem B ; 128(1): 340-349, 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-38152041

ABSTRACT

Benzocyclobutene (BCB)-based resins have garnered considerable attention because of their remarkable dielectric properties and thermal stability. However, in molecular dynamics (MD) simulations, progress in BCB-based resin research has yet to keep pace with experimental advancements, resulting in a shortage of theoretical underpinnings at the molecular level. This study focuses on a novel homopolymer, poly(2-(4-benzocyclobutenyl)-divinylbenzene(DVB-S-BCB)), and devises an interactive methodology suitable for BCB-based resins. We implemented a Python script for the joint relaxation method to construct a three-dimensional model of the cured polymer using MadeA and LAMMPS. We conducted MD simulations to investigate how the cross-linking degree and resin molecular weight influence the dielectric properties of the cured polymer. Furthermore, we analyzed the thermodynamic properties through simulation. The results illustrate that augmenting the cross-linking degree and resin molecular weight results in a higher cross-linking density and reduced free volume, thereby increasing the dielectric constant of the resin. The cross-link density does not increase indefinitely with molecular weight, and after a certain threshold is reached, it cannot have a significant effect on the dielectric constant. The degree of cross-linking exerts a more pronounced impact on the dielectric constant than the molecular weight of the resin. In addition, the simulation results denote the excellent thermodynamic properties of the cured polymer. This study also examines the dielectric and thermodynamic properties of the resin samples that were experimentally prepared. The obtained data successfully confirm the reliability of the simulation results. This study offers novel insights for future simulation research on benzocyclobutene-based resins. Additionally, it provides theoretical support for exploring experimental work on low-dielectric materials in the electronic field.

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