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1.
J Phys Condens Matter ; 36(30)2024 May 03.
Article in English | MEDLINE | ID: mdl-38653319

ABSTRACT

By using the tight-binding Hamiltonian and non-equilibrium Green's function methods, the Seebeck and Nernst effects ofα-T3lattice are investigated, in which the lattice interpolates between graphene and the dice lattice via the parameterα. Forα= 0 (graphene), flat bands are always present in the band structure. The Seebeck and Nernst coefficients are consistent with those in graphene. Whenαis non-zero at zero magnetic field, the Seebeck coefficient is an odd function of the Fermi energy. It produces a very large and wide first peak within the band gap for the zigzag boundary. Under the influence of magnetic fields, the first peak of the Seebeck coefficient in the gap region increases withαincreasing. The Nernst effect occurs under the influence of a magnetic field. The height of the zeroth peak of the Nernst coefficient increases withαincreasing. Whenαreaches a certain value, the zeroth peak splits. The post-split peak decreases withαincreasing for the zigzag boundary, but continues to become wider and higher for the armchair boundary.

2.
Mol Med Rep ; 29(1)2024 Jan.
Article in English | MEDLINE | ID: mdl-37937668

ABSTRACT

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the VEGF western blotting data shown in Fig. 4A on p. 3392 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes.  Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received a reply.The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 3387­3394, 2017; DOI: 10.3892/mmr.2017.6995].

3.
Biomed Environ Sci ; 36(11): 1059-1067, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-38098325

ABSTRACT

Objective: To explore the association between socioeconomic status (SES) and postoperative outcomes in patients with chronic sinusitis (CRS) after functional endoscopic sinus surgery (ESS). Methods: We conducted an observational cohort study of 1,047 patients with CRS undergoing ESS. Discharged patients were followed up to 72 weeks for all-cause recurrence events. Baseline SES was established based on occupation, education level, and family income of the patients 1 year before the operation. Kaplan-Meier method was used to calculate the recovery rate after ESS, and Cox proportional hazards regression analysis was used to evaluate the relationship between SES and prognosis. Results: Patients of middle SES had lower unadjusted all-cause recurrence than those of low or high SES; 24-week overall recovery rate was 90.4% [95 % confidence interval ( CI): 89.6%-91.2%] in patients of middle SES, 13.5% (95 % CI: 12.8%-14.2%) in patients of low SES, and 31.7% (95 % CI: 30.7%-32.7%) in patients of high SES (both log-rank P < 0.001). After adjustment for covariates, hazard ratios ( HRs) were 7.69 (95 % CI: 6.17-9.71, P trend < 0.001) for all-cause recurrence for low SES versus middle SES, and 6.19 (95 % CI: 4.78-7.93, P trend < 0.001) for middle SES versus high SES. Conclusion: Low SES and high SES were more associated with the worse prognosis of CRS patients after ESS than middle SES.


Subject(s)
Rhinosinusitis , Sinusitis , Humans , Cohort Studies , Sinusitis/surgery , Social Class , Endoscopy/methods , Chronic Disease , Treatment Outcome
4.
Heliyon ; 9(12): e23002, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38144322

ABSTRACT

Background: Neurodegenerative retinal diseases such as retinitis pigmentosa are serious disorders that may cause irreversible visual impairment. Ferroptosis is a novel type of programmed cell death, and the involvement of ferroptosis in retinal degeneration is still unclear. This study aimed to investigate the related ferroptosis genes in a mice model of retinal degeneration induced by light damage. Methods: A public dataset of GSE10528 deriving from the Gene Expression Omnibus database was analyzed to identify the differentially expressed genes (DEGs). Gene set enrichment analysis between light damage and control group was conducted. The differentially expressed ferroptosis-related genes (DE-FRGs) were subsequently identified by intersecting the DEGs with a ferroptosis genes dataset retrieved from the FerrDb database. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were further performed using the DE-FRGs. A protein-protein interaction (PPI) network was constructed to identify hub ferroptosis-related genes (HFRGs). The microRNAs (miRNAs)-HFRGs, transcription factors (TFs)-HFRGs networks as well as target drugs potentially interacting with HFRGs were analyzed utilizing bioinformatics algorithms. Results: A total of 932 DEGs were identified between the light damage and control group. Among these, 25 genes were associated with ferroptosis. GO and KEGG analyses revealed that these DE-FRGs were mainly enriched in apoptotic signaling pathway, response to oxidative stress and autophagy, ferroptosis, necroptosis and cytosolic DNA-sensing pathway. Through PPI network analysis, six hub ferroptosis-related genes (Jun, Stat3, Hmox1, Atf3, Hspa5 and Ripk1) were ultimately identified. All of them were upregulated in light damage retinas, as verified by the GSE146176 dataset. Bioinformatics analyses predicated that 116 miRNAs, 23 TFs and several potential therapeutic compounds might interact with the identified HFRGs. Conclusion: Our study may provide novel potential biomarkers, therapeutic targets and new insights into the ferroptosis landscape in retinal neurodegenerative diseases.

5.
Sci Rep ; 13(1): 19107, 2023 11 04.
Article in English | MEDLINE | ID: mdl-37925591

ABSTRACT

TGFB1, which encodes TGF-ß1, a potent cytokine regulating varies cellular processes including immune responses. TGF-ß1 plays context-dependent roles in cancers and is increasingly recognized as a therapeutic target to enhance immunotherapy responses. We comprehensively evaluated expression of TGFB1 and its clinical and biological effects across hematological malignancies. TGFB1 expression was first explored using data from the GTEx, CCLE, and TCGA databases. The expression and clinical significances of TGFB1 in hematological malignancies were analyzed using Hemap and our In Silico curated datasets. We also analyzed the relationship between TGFB1 with immune scores and immune cell infiltrations in Hemap. We further assessed the value of TGFB1 in predicting immunotherapy response using TIDE and real-world immunotherapy datasets. TGFB1 showed a hematologic-tissue-specific expression pattern both across normal tissues and cancer types. TGFB1 expression were broadly dysregulated in blood cancers and generally associated with adverse prognosis. TGFB1 expression were associated with distinct TME properties among different blood cancer types. In addition, TGFB1 expression was found to be a useful marker in predicting immunotherapy responses. Our results suggest that TGFB1 is broadly dysregulated in hematological malignancies. TGFB1 might regulate the immune microenvironment in a cancer-type-specific manner, which could be applied in the development of new targeted drugs for immunotherapy.


Subject(s)
Hematologic Neoplasms , Transforming Growth Factor beta1 , Humans , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolism , Cytokines , Prognosis , Hematologic Neoplasms/genetics , Tumor Microenvironment/genetics , Immunotherapy
6.
Biomed Environ Sci ; 36(8): 779-782, 2023 Aug 20.
Article in English | MEDLINE | ID: mdl-37711091

ABSTRACT

In August 2021, three students with diarrhea from the same school visited a local hospital in the S district of Beijing. An epidemic investigation showed that there were more students with diarrhea in the same school and they had one meal together. Campylobacter jejuni was isolated from both patients with diarrhea and asymptomatic food handlers; however, the latter also carried Campylobacter coli. Phylogenomic analysis showed that there was a campylobacteriosis outbreak among the students, and the asymptomatic food handler may have been the source of the infection. Routine inspection and surveillance for Campylobacter is needed for the food producing staff, particularly those cooking in the cafeteria in schools or other public food services.


Subject(s)
Campylobacter Infections , Campylobacter , Gastroenteritis , Humans , Campylobacter Infections/epidemiology , Diarrhea , Disease Outbreaks
7.
Heliyon ; 9(6): e17061, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37389042

ABSTRACT

Purpose: Colonoscopy is often accompanied by short-term postoperative cognitive decline. We aimed to explore whether single-use alfentanil for patients undergoing elective colonoscopy could reduce cognitive impairment at discharge compared with propofol. Patients and methods: 172 adult patients undergoing elective colonoscopy were randomized to receive intravenous propofol at 2 mg/kg (group P) or alfentanil at 10 µg/kg (group A); 40 healthy volunteers were included in the blank group. Cognitive function was considered the primary outcome and was measured using five neuropsychological tests before sedation and discharge. The z-score method was used to determine cognitive dysfunction according to z-score >1.96 in two types of neuropsychological tests. Other outcomes included discharge time, vital signs, associated adverse events during colonoscopy, and the satisfaction level of patients and endoscopic physicians. Results: 164 patients (78 in group A and 86 in group P) completed the study protocol. At discharge, the incidence of cognitive dysfunction in group P was 23% and was significantly lower in the alfentanil group (2.5%), with a relative risk of 0.11 (95% confidence interval: 0.03-0.46, P < 0.001). The incidence of hypotension in group A was lower than that in group P (3.8% vs 22.1%, relative risk = 0.17 [95% confidence interval: 0.05-0.46, P = 0.001]), and the discharge time in group A was shorter than that in group P (5 [(Rutter and et al., 2016; Zhang and et al., 2013; Hirsh and et al., 2006; Zhou and et al., 2021; Singh and et al., 2008; Ko and et al., 2010; Sargin et al., 2019) 3-93-9 vs 13 [(Ekmekci and et al., 2017; Eberl and et al., 2012; Eberl and et al., 2014; N'Kaoua and et al., 2002; Chung et al., 1995; Berger and et al., 2019; Quan and et al., 2019; Deng and et al., 2021; Gualtieri and Johnson, 2006) 10-1810-18 min, P < 0.001). Conclusion: For patients undergoing colonoscopy, single-use alfentanil causes less damage to postoperative cognitive function, less risk of hypotension, and shorter discharge time than propofol.

8.
In Vitro Cell Dev Biol Anim ; 59(4): 241-255, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37099179

ABSTRACT

Gene-knockout pigs have important applications in agriculture and medicine. Compared with CRISPR/Cas9 and cytosine base editing (CBE) technologies, adenine base editing (ABE) shows better safety and accuracy in gene modification. However, because of the characteristics of gene sequences, the ABE system cannot be widely used in gene knockout. Alternative splicing of mRNA is an important biological mechanism in eukaryotes for the formation of proteins with different functional activities. The splicing apparatus recognizes conserved sequences of the 5' end splice donor and 3' end splice acceptor motifs of introns in pre-mRNA that can trigger exon skipping, leading to the production of new functional proteins, or causing gene inactivation through frameshift mutations. This study aimed to construct a MSTN knockout pig by inducing exon skipping with the aid of the ABE system to expand the application of the ABE system for the preparation of knockout pigs. In this study, first, we constructed ABEmaxAW and ABE8eV106W plasmid vectors and found that their editing efficiencies at the targets were at least sixfold and even 260-fold higher than that of ABEmaxAW by contrasting the editing efficiencies at the gene targets of endogenous CD163, IGF2, and MSTN in pigs. Subsequently, we used the ABE8eV106W system to realize adenine base (the base of the antisense strand is thymine) editing of the conserved splice donor sequence (5'-GT) of intron 2 of the porcine MSTN gene. A porcine single-cell clone carrying a homozygous mutation (5'-GC) in the conserved sequence (5'-GT) of the intron 2 splice donor of the MSTN gene was successfully generated after drug selection. Unfortunately, the MSTN gene was not expressed and, therefore, could not be characterized at this level. No detectable genomic off-target edits were identified by Sanger sequencing. In this study, we verified that the ABE8eV106W vector had higher editing efficiency and could expand the editing scope of ABE. Additionally, we successfully achieved the precise modification of the alternative splice acceptor of intron 2 of the porcine MSTN gene, which may provide a new strategy for gene knockout in pigs.


Subject(s)
Adenine , Gene Editing , Animals , Swine , Exons/genetics , Mutation , Gene Knockout Techniques
9.
Asian J Surg ; 46(1): 58-65, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35589479

ABSTRACT

Acute invasive fungal rhinosinusitis (AIFR) is a rare disease, but the prognosis is by no means ideal. Pathologically, fungal infection is not only located in the sinus cavity, but also invades the sinus mucosa and bone wall, the surrounding structures and tissues such as the orbit and anterior skull base are often compromised and are accompanied with intracranial and extracranial complications. Despite decades of efforts, acute invasive fungal rhinosinusitis remains a devastating disease, the mortality of the disease continues to hover around 50%. The main impediments to improving the prognosis of acute invasive fungal rhinosinusitis are the difficulties of early diagnosis and the rapid reversal of immune insufficiency. Moreover, aggressive surgery combined with systemic antifungal therapy are significant positive prognostic factors as well. Progress and standardization of AIFR treatment protocols have been limited by the scarcity of the disease and the absence of published randomized studies. Therewith, how to improve the therapeutic outcome and reduce the mortality rate has always been a challenging clinical discussion. We have summarized the relevant case series and literature from the recent years, management with optimal diagnostic and curative strategies are reviewed.


Subject(s)
Mycoses , Paranasal Sinuses , Rhinitis , Sinusitis , Humans , Rhinitis/therapy , Rhinitis/surgery , Sinusitis/diagnosis , Sinusitis/therapy , Sinusitis/microbiology , Mycoses/diagnosis , Mycoses/therapy , Acute Disease
10.
Front Pharmacol ; 13: 993506, 2022.
Article in English | MEDLINE | ID: mdl-36188598

ABSTRACT

The role of daytime variation in the comprehensive pharmaceutical effects of commonly used opioid analgesics in clinical setting remains unclear. This study aimed to explore the differences in daytime variation among elective surgery patients who were scheduled to receive preemptive analgesia with equivalent doses of sufentanil, dezocine, and tramadol in the morning and afternoon. The analgesic effect was assessed by changes in the pressure pain threshold before and after intravenous administration of sufentanil, dezocine, and tramadol. Respiratory effects were evaluated using pulse oximetry, electrical impedance tomography, and arterial blood gas analysis. Other side effects, including nausea, sedation, and dizziness, were also recorded, and blood concentration was measured. The results showed that the analgesic effects of sufentanil, dezocine, and tramadol were significantly better in the morning than in afternoon. In the afternoon, sufentanil had a stronger sedative effect, whereas dezocine had a stronger inhibitory respiratory effect. The incidence of nausea was higher in the morning with tramadol. Additionally, significant differences in different side effects were observed among three opioids. Our results suggest that the clinical use of these three opioids necessitates the formulation of individualized treatment plans, accounting for different administration times, to achieve maximum analgesic effect with minimal side effects.

11.
Microb Pathog ; 170: 105723, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35981694

ABSTRACT

Porcine deltacoronavirus (PDCoV) is an emenging swine enteropathogenic coronavirus that can cause high mortality rate. It affects pigs of all ages, but most several in neonatal piglets. Little is known regarding the pathogenicity of PDCoV against 27-day-old piglets. In this study, 27-day-old piglets were experimentally infected with PDCoV CZ2020 from cell culture, the challenged piglets do not have obvious symptoms from 1 to 7 days post-challenge (DPC), while viral shedding was detected in rectal swab at 1 DPC. Tissues of small intestines displayed slight macroscopic and microscopic lesions with no viral antigen detection. On the other hand, 27-day-old piglets were infected with PDCoV from intestinal contents, the piglets developed mild to severe diarrhea, shedding increasing from 2 to 7 DPC, and developed macroscopic and microscopic lesions in small intestines with clear viral antigen confirmed by immunohistochemistry staining. Indicating the small intestine was still the major target organ in PDCoV-challenged pigs at the age of 27-day-old. Diarrhea caused by PDCoV from intestinal contents in 27-day-old piglets is less reported. Thus, our results might provide new insights into the pathogenesis of PDCoV.


Subject(s)
Swine Diseases , Animals , Cell Culture Techniques , Deltacoronavirus , Diarrhea/pathology , Gastrointestinal Contents , Swine , Virulence
12.
ACS Appl Mater Interfaces ; 14(35): 40322-40330, 2022 Sep 07.
Article in English | MEDLINE | ID: mdl-35994422

ABSTRACT

Developing a smart responsive surface for on-demand delivery of organic, inorganic, and biological cargo in vitro cellular uptake is always in constant demand. Herein, we present carbon quantum dot (CQD)-loaded (poly(N-isopropylacrylamide) (PNIPAAm)/poly(methyl methacrylate (PMMA)) blend nanofiber sheets having a thermoresponsive nature. As a model cargo, fluorescent CQDs are used for the demonstration of the on-demand delivery mechanism. In addition, a thermoresponsive nature is produced by the PNIPAAm polymer in the nanofiber matrix while the PMMA polymer provides extra stability and firmness to the nanofibers against the sudden dissolution of the nanofibers in aqueous media. The synthesis of CQDs and their loading into a blend nanofiber matrix are confirmed using fluorescence spectrophotometry, transmission electron microscopy, and fluorescence microscopy. The morphologies and diameters of the nanofibers are analyzed by scanning electron microscopy. Burst effect analysis proves that 30% (w/w) PNIPAAm-containing nanofibers possess the highest stability with the least dissolution in aqueous media. Thermoresponsiveness of the nanofibers is further confirmed through water contact angle measurements. Quantitative fluorescence results show that more than 80% of loaded CQDs can be released upon thermal stimulation. The fluorescence micrographs reveal that the blend nanofiber sheets can effectively improve the cellular uptake of CQDs by simply increasing the local concentrations via applying thermal stimulation as the released mechanism.


Subject(s)
Nanofibers , Quantum Dots , Carbon , Polymers , Polymethyl Methacrylate
13.
Bioengineered ; 13(5): 13293-13299, 2022 05.
Article in English | MEDLINE | ID: mdl-35635032

ABSTRACT

T helper 17 (Th17) cells regulate inflammatory processes and are implicated in pathogenesis of proliferative diabetic retinopathy (PDR) through modulation of interleukin-17 (IL-17). IL-35, anti-inflammatory factor, negatively mediates IL-17 expression and Th17 differentiation. In this study, the role of IL-35 in PDR was assessed. The results showed that IL-35 was down-regulated, while IL-17 was up-regulated, in peripheral blood mononuclear cells (PBMCs) of PDR patients. In addition, immunofluorescence analysis indicated that frequency of Th17 cells was enhanced in the PBMCs of PDR patients. However, incubation with IL-35 reduced the Th17 cell frequency and decreased the level of IL-17 in CD4+ T lymphocytes. Moreover, the levels of transcription factors essential for Th17 differentiation, ROR α (retinoid-related orphan receptor alpha) and ROR γt, were reduced by IL-35 treatment. In conclusion, IL-35 reduced level of IL-17 and inhibited Th17 differentiation to protect against PDR.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Cell Differentiation , Diabetic Retinopathy/genetics , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/pathology , Humans , Interleukin-17/genetics , Interleukin-17/metabolism , Leukocytes, Mononuclear , Th17 Cells/metabolism
14.
Front Neurosci ; 16: 810166, 2022.
Article in English | MEDLINE | ID: mdl-35368259

ABSTRACT

Objective: The diurnal rhythm profile of human basal pain sensitivity and its association with sympathetic nerve activity are not fully understood. This study aimed to examine rhythmic changes in experimental pain sensitivity and skin sympathetic nerve activity in healthy volunteers. Methods: Thirty healthy volunteers were included in the study. Experimental pain sensitivity, including pressure pain threshold and tolerance, cold pain threshold (CPT) and tolerance, skin sympathetic nerve activity, and cardiovascular parameters (including heart rate, cardiac output, and peripheral vascular resistance) at six time points throughout the day (08:00, 12:00, 16:00, 20:00, 00:00, and 04:00) were sequentially measured. Circadian rhythm analysis was performed on the mean values of the different measurements and individual subjects. Results: Significant differences were found in experimental pain sensitivity, skin sympathetic nerve activity, and non-invasive cardiovascular parameters at different time points (P < 0.05). The minimum measured values of all four types of experimental pain sensitivity were consistently observed at 04:00. Rhythmical analysis showed that the mean values of pressure pain threshold (meta2d P = 0.016) and skin sympathetic nerve activity (meta2d P = 0.039) were significant. Significant diurnal rhythms in pain sensitivity and skin sympathetic nerve activity existed in some individuals but not in others. No significant correlation between experimental pain sensitivity and skin sympathetic nerve activity was found at any time point (P > 0.05). Conclusion: Significant diurnal fluctuations were observed in different pain sensitivities and skin sympathetic nerve activity. No significant correlation between experimental pain sensitivity and sympathetic excitability at different times was found; the reasons for these phenomena remain to be further studied. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2000039709].

15.
Transl Vis Sci Technol ; 11(2): 19, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-35142784

ABSTRACT

PURPOSE: This study aims to elucidate the role and mechanism of survivin and FOXP1 in scarring after glaucoma surgery and to evaluate the prevention and treatment of excessive wound healing and scar formation in an in vitro model of glaucoma filtration surgery. METHODS: Human Tenon's capsule fibroblasts (HTFs) were used with TGF-ß to establish an in vitro cell model after glaucoma, observe survivin expression in the cell model, and observe HTFs proliferation after treatment with survivin inhibitor YM155 and the expression of α-SMA and collagen type I. In addition, the effects of survivin and cell proliferation in HTFs after knockdown of FOXP1 were observed by Western blot analysis. RESULTS: Survivin was upregulated in HTFs after glaucoma surgery, and it could promote the cell proliferation of HTFs. After treatment with its inhibitor YM155, the cell proliferation of HTFs was inhibited, and the expression of α-SMA and collagen type I were decreased. The results showed that in knockdown of FOXP1, the expression of survivin was downregulated, and the cell proliferation of HTFs was significantly reduced. CONCLUSIONS: This study demonstrates that targeting survivin with an inhibitory YM155 reduced fibrosis and the extracellular matrix (ECM), and it was regulated by the FOXP1 transcription factor. These results suggest that survivin could be a potential target for treating scar formation after glaucoma surgery. TRANSLATIONAL RELEVANCE: Together with the results from previous survivin and FOXP1 preclinical studies, these data support the evaluation of this gene therapy candidate in clinical trials as a potential durable treatment for antiscarring of glaucoma surgery.


Subject(s)
Cicatrix , Glaucoma , Cells, Cultured , Cicatrix/metabolism , Cicatrix/pathology , Cicatrix/prevention & control , Collagen Type I , Forkhead Transcription Factors/genetics , Glaucoma/surgery , Humans , Repressor Proteins/genetics , Survivin/genetics , Transcription Factors
16.
Biotechnol Lett ; 44(1): 59-76, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34997407

ABSTRACT

Gene-knockout pigs have important applications in agriculture and medicine. Compared with CRISPR/Cas9, Adenine base editor (ABE) convert single A·T pairs to G·C pairs in the genome without generating DNA double-strand breaks, and this method has higher accuracy and biosafety in pig genetic modification. However, the application of ABE in pig gene knockout is limited by protospacer-adjacent motif sequences and the base-editing window. Alternative mRNA splicing is an important mechanism underlying the formation of proteins with diverse functions in eukaryotes. Spliceosome recognizes the conservative sequences of splice donors and acceptors in a precursor mRNA. Mutations in these conservative sequences induce exon skipping, leading to proteins with novel functions or to gene inactivation due to frameshift mutations. In this study, adenine base-editing-mediated exon skipping was used to expand the application of ABE in the generation of gene knockout pigs. We first constructed a modified "all-in-one" ABE vector suitable for porcine somatic cell transfection that contained an ABE for single-base editing and an sgRNA expression cassette. The "all-in-one" ABE vector induced efficient sgRNA-dependent A-to-G conversions in porcine cells during single base-editing of multiple endogenous gene loci. Subsequently, an ABE system was designed for single adenine editing of the conservative splice acceptor site (AG sequence at the 3' end of the intron 5) and splice donor site (GT sequence at the 5' end of the intron 6) in the porcine gene GHR; this method achieved highly efficient A-to-G conversion at the cellular level. Then, porcine single-cell colonies carrying a biallelic A-to-G conversion in the splice acceptor site in the intron 5 of GHR were generated. RT-PCR indicated exon 6 skipped at the mRNA level. Western blotting revealed GHR protein loss, and gene sequencing showed no sgRNA-dependent off-target effects. These results demonstrate accurate adenine base-editing-mediated exon skipping and gene knockout in porcine cells. This is the first proof-of-concept study of adenine base-editing-mediated exon skipping for gene regulation in pigs, and this work provides a new strategy for accurate and safe genetic modification of pigs for agricultural and medical applications.


Subject(s)
Adenine , Gene Editing , Adenine/metabolism , Animals , CRISPR-Cas Systems/genetics , Cell Line , Exons/genetics , Gene Editing/methods , Gene Knockout Techniques , Swine
17.
Neurosci Bull ; 38(2): 135-148, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34542799

ABSTRACT

The family of voltage-gated potassium Kv2 channels consists of the Kv2.1 and Kv2.2 subtypes. Kv2.1 is constitutively highly phosphorylated in neurons and its function relies on its phosphorylation state. Whether the function of Kv2.2 is also dependent on its phosphorylation state remains unknown. Here, we investigated whether Kv2.2 channels can be phosphorylated by protein kinase C (PKC) and examined the effects of PKC-induced phosphorylation on their activity and function. Activation of PKC inhibited Kv2.2 currents and altered their steady-state activation in HEK293 cells. Point mutations and specific antibodies against phosphorylated S481 or S488 demonstrated the importance of these residues for the PKC-dependent modulation of Kv2.2. In layer II pyramidal neurons in cortical slices, activation of PKC similarly regulated native Kv2.2 channels and simultaneously reduced the frequency of action potentials. In conclusion, this study provides the first evidence to our knowledge that PKC-induced phosphorylation of the Kv2.2 channel controls the excitability of cortical pyramidal neurons.


Subject(s)
Protein Kinase C , Pyramidal Cells/enzymology , Shab Potassium Channels , Action Potentials , HEK293 Cells , Humans , Protein Kinase C/metabolism , Shab Potassium Channels/genetics
18.
Neuroscience Bulletin ; (6): 135-148, 2022.
Article in English | WPRIM (Western Pacific) | ID: wpr-922667

ABSTRACT

The family of voltage-gated potassium Kv2 channels consists of the Kv2.1 and Kv2.2 subtypes. Kv2.1 is constitutively highly phosphorylated in neurons and its function relies on its phosphorylation state. Whether the function of Kv2.2 is also dependent on its phosphorylation state remains unknown. Here, we investigated whether Kv2.2 channels can be phosphorylated by protein kinase C (PKC) and examined the effects of PKC-induced phosphorylation on their activity and function. Activation of PKC inhibited Kv2.2 currents and altered their steady-state activation in HEK293 cells. Point mutations and specific antibodies against phosphorylated S481 or S488 demonstrated the importance of these residues for the PKC-dependent modulation of Kv2.2. In layer II pyramidal neurons in cortical slices, activation of PKC similarly regulated native Kv2.2 channels and simultaneously reduced the frequency of action potentials. In conclusion, this study provides the first evidence to our knowledge that PKC-induced phosphorylation of the Kv2.2 channel controls the excitability of cortical pyramidal neurons.


Subject(s)
Humans , Action Potentials , HEK293 Cells , Protein Kinase C/metabolism , Pyramidal Cells/enzymology , Shab Potassium Channels/genetics
19.
BMJ Open ; 11(12): e048876, 2021 12 15.
Article in English | MEDLINE | ID: mdl-34911709

ABSTRACT

OBJECTIVE: To identify the factors associated with the survival of malignant Hodgkin and non-Hodgkin lymphomas in oral and nasal cavities.Study design. Retrospective cohort survival analysis. METHODS: The Surveillance, Epidemiology and End Results 18 database was used to analyse the factors associated with the 5-year survival rate of malignant lymphomas diagnosed in the oral cavity and pharynx (OCP) and nasal cavity and sinus (NCS) regions from 1988 to 2011 for all patients in the USA. Multivariable Cox regression models were used to calculate the HR of malignant lymphoma death overall and by the site of cancer diagnosis. RESULTS: Among the 8785 patients included in the analysis, 4103 (46.7%) were women, 6096 (69.4%) were non-Hispanic (NH) white, 635 (7.2%) were NH black and 1209 (13.8%) were Hispanic patients of all races. We found that a higher 5-year survival rate of malignant lymphoma is associated with: female gender; younger age at diagnosis; NH white race/ethnicity; diagnosis in the oral cavity; receiving surgery/radiation and surgery/radiation, surgery and chemotherapy as the treatment; diagnosis at a localised stage and diagnosis in later calendar years. No association with lymphoma subtype was observed. CONCLUSION: We have identified several demographics and prognosis factors associated with the 5-year survival rate of malignant lymphomas in the OCP and NCS regions. These findings warrant greater public health attention on the prognosis of malignant lymphomas in the OCP and NCS regions among the most vulnerable populations.


Subject(s)
Lymphoma , Nasal Cavity , Cohort Studies , Female , Humans , Lymphoma/epidemiology , Prognosis , Retrospective Studies , Survival Analysis , Survival Rate , United States/epidemiology
20.
BMC Med Inform Decis Mak ; 21(1): 284, 2021 10 16.
Article in English | MEDLINE | ID: mdl-34656109

ABSTRACT

Charging according to disease is an important way to effectively promote the reform of medical insurance mechanism, reasonably allocate medical resources and reduce the burden of patients, and it is also an important direction of medical development at home and abroad. The cost forecast of single disease can not only find the potential influence and driving factors, but also estimate the active cost, and tell the management and reasonable allocation of medical resources. In this paper, a method of Bayesian network combined with regression analysis is proposed to predict the cost of treatment based on the patient's electronic medical record when the amount of data is small. Firstly, a set of text-based medical record data conversion method is established, and in the clustering method, the missing value interpolation is carried out by weighted method according to the distance, which completes the data preparation and processing for the realization of data prediction. Then, aiming at the problem of low prediction accuracy of traditional regression model, this paper establishes a prediction model combined with local weight regression method after Bayesian network interpretation and classification of patients' treatment process. Finally, the model is verified with the medical record data provided by the hospital, and the results show that the model has higher prediction accuracy.


Subject(s)
Electronic Health Records , Health Care Costs , Bayes Theorem , Cluster Analysis , Humans , Regression Analysis
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