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1.
J Med Genet ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38663984

RESUMO

BACKGROUND: Clubfoot, presenting as a rigid inward and downward turning of the foot, is one of the most common congenital musculoskeletal anomalies. The aetiology of clubfoot is poorly understood and variants in known clubfoot disease genes account for only a small portion of the heritability. METHODS: Exome sequence data were generated from 1190 non-syndromic clubfoot cases and their family members from multiple ethnicities. Ultra-rare variant burden analysis was performed comparing 857 unrelated clubfoot cases with European ancestry with two independent ethnicity-matched control groups (1043 in-house and 56 885 gnomAD controls). Additional variants in prioritised genes were identified in a larger cohort, including probands with non-European ancestry. Segregation analysis was performed in multiplex families when available. RESULTS: Rare variants in 29 genes were enriched in clubfoot cases, including PITX1 (a known clubfoot disease gene), HOXD12, COL12A1, COL9A3 and LMX1B. In addition, rare variants in posterior HOX genes (HOX9-13) were enriched overall in clubfoot cases. In total, variants in these genes were present in 8.4% (100/1190) of clubfoot cases with both European and non-European ancestry. Among these, 3 are de novo and 22 show variable penetrance, including 4 HOXD12 variants that segregate with clubfoot. CONCLUSION: We report HOXD12 as a novel clubfoot disease gene and demonstrate a phenotypic expansion of known disease genes (myopathy gene COL12A1, Ehlers-Danlos syndrome gene COL9A3 and nail-patella syndrome gene LMX1B) to include isolated clubfoot.

2.
Redox Biol ; 72: 103157, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38631119

RESUMO

BACKGROUND: Doxorubicin (DOX) is a chemotherapeutic drug, while its clinical use is greatly limited by the life-threatening cardiotoxicity. N6-methyladenosine (m6A) RNA modification participates in varieties of cellular processes. Nonetheless, it remains elusive whether m6A modification and its methyltransferase METTL3 are involved in the progression of DOX-induced cardiotoxicity (DIC). METHODS: Mice were administrated with DOX (accumulative dosage of 20 mg/kg) repeatedly to establish a chronic DIC model. Cardiomyocyte-specific conditional METTL3 knockout mice were employed to evaluate the effects of altered m6A RNA modification on DIC. The effects of METTL3 on cardiomyocyte ferroptosis were also examined in response to DOX stimulation. RESULTS: DOX led to increased levels in m6A modification and METTL3 expression in cardiomyocytes in a c-Jun-dependent manner. METTL3-knockout mice exhibited improved cardiac function, remodeling and injury following DOX insult. Besides, inhibition of METTL3 alleviated DOX-induced iron accumulation and ferroptosis in cardiomyocytes, whereas METTL3 overexpression exerted the opposite effects. Mechanistically, METTL3 promoted m6A modification of TFRC mRNA, a critical gene governing iron uptake, and enhanced its stability through recognition of the m6A reader protein, IGF2BP2. Moreover, pharmacological administration of a highly selective METTL3 inhibitor STM2457 effectively ameliorated DIC in mice. CONCLUSION: METTL3 plays a cardinal role in the etiology of DIC by regulating cardiac iron metabolism and ferroptosis through TFRC m6A modification. Inhibition of METTL3 might be a potential therapeutic avenue for DIC.

3.
BMC Nurs ; 23(1): 255, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649929

RESUMO

BACKGROUND: Poor nurse-patient relationship poses an obstacle to care delivery, jeopardizing patient experience and patient care outcomes. Measuring nurse-patient relationship is challenging given its multi-dimensional nature and a lack of well-established scales. PURPOSE: This study aimed to develop a multi-dimensional scale measuring nurse-patient relationship in China. METHODS: A preliminary scale was constructed based on the existing literature and Delphi consultations with 12 nursing experts. The face validity of the scale was tested through a survey of 45 clinical nurses. This was followed by a validation study on 620 clinical nurses. Cronbach's α, content validity and known-group validity of the scale were assessed. The study sample was further divided into two for Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA), respectively, to assess the construct validity of the scale. RESULTS: The Nurse-Patient Relationship Scale (NPRS) containing 23 items was developed and validated, measuring five dimensions: nursing behavior, nurse understanding and respect for patient, patient misunderstanding and mistrust in nurse, communication with patient, and interaction with patient. The Cronbach's α of the NPRS ranged from 0.725 to 0.932, indicating high internal consistency. The CFA showed excellent fitness of data into the five-factor structure: χ2/df = 2.431, GFI = 0.933, TLI = 0.923, CFI = 0.939, IFI = 0.923, RMSEA = 0.070. Good content and construct validity are demonstrated through expert consensus and psychometric tests. CONCLUSION: The NPRS is a valid tool measuring nurse-patient relationship in China.

4.
Front Immunol ; 15: 1377270, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585268

RESUMO

Introduction: Signal peptide peptidase (SPP) is an intramembrane protease involved in a variety of biological processes, it participates in the processing of signal peptides after the release of the nascent protein to regulate the endoplasmic reticulum associated degradation (ERAD) pathway, binds misfolded membrane proteins, and aids in their clearance process. Additionally, it regulates normal immune surveillance and assists in the processing of viral proteins. Although SPP is essential for many viral infections, its role in silkworms remains unclear. Studying its role in the silkworm, Bombyx mori , may be helpful in breeding virus-resistant silkworms. Methods: First, we performed RT-qPCR to analyze the expression pattern of BmSPP. Subsequently, we inhibited BmSPP using the SPP inhibitor 1,3-di-(N-carboxybenzoyl-L-leucyl-L-leucylaminopropanone ((Z-LL)2-ketone) and downregulated the expression of BmSPP using CRISPR/Cas9 gene editing. Furthermore, we assessed the impact of these interventions on the proliferation of Bombyx mori nucleopolyhedrovirus (BmNPV). Results: We observed a decreased in the expression of BmSPP during viral proliferation. It was found that higher concentration of the inhibitor resulted in greater inhibition of BmNPV proliferation. The down-regulation of BmSPP in both in vivo and in vitro was found to affect the proliferation of BmNPV. In comparison to wild type silkworm, BmSPPKO silkworms exhibited a 12.4% reduction in mortality rate. Discussion: Collectively, this work demonstrates that BmSPP plays a negative regulatory role in silkworm resistance to BmNPV infection and is involved in virus proliferation and replication processes. This finding suggests that BmSPP servers as a target gene for BmNPV virus resistance in silkworms and can be utilized in resistance breeding programs.


Assuntos
Bombyx , Nucleopoliedrovírus , Animais , Nucleopoliedrovírus/genética , Edição de Genes , Regulação para Baixo
5.
Anal Chem ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38632870

RESUMO

Hepatitis B virus (HBV) is a major cause of liver cirrhosis and hepatocellular carcinoma, with HBV surface antigen (HBsAg) being a crucial marker in the clinical detection of HBV. Due to the significant harm and ease of transmission associated with HBV, HBsAg testing has become an essential part of preoperative assessments, particularly for emergency surgeries where healthcare professionals face exposure risks. Therefore, a timely and accurate detection method for HBsAg is urgently needed. In this study, a surface-enhanced Raman scattering (SERS) sensor with a sandwich structure was developed for HBsAg detection. Leveraging the ultrasensitive and rapid detection capabilities of SERS, this sensor enables quick detection results, significantly reducing waiting times. By systematically optimizing critical factors in the detection process, such as the composition and concentration of the incubation solution as well as the modification conditions and amount of probe particles, the sensitivity of the SERS immune assay system was improved. Ultimately, the sensor achieved a sensitivity of 0.00576 IU/mL within 12 min, surpassing the clinical requirement of 0.05 IU/mL by an order of magnitude. In clinical serum assay validation, the issue of false positives was effectively addressed by adding a blocker. The final sensor demonstrated 100% specificity and sensitivity at the threshold of 0.05 IU/mL. Therefore, this study not only designed an ultrasensitive SERS sensor for detecting HBsAg in actual clinical serum samples but also provided theoretical support for similar systems, filling the knowledge gap in existing literature.

6.
J Dermatolog Treat ; 35(1): 2338281, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38632962

RESUMO

BACKGROUND: Granuloma formation is an uncommon and persistent skin inflammatory condition caused by the injection of dermal fillers. The exact cause of this reaction is not well understood, but it may be associated with irritating components or abnormal immune function. Treating granulomas can be difficult. However, recent research has shown that Janus kinase (JAK) inhibitors hold promise as a potential therapy for refractory granulomatous diseases. OBJECTIVES: The aim was to evaluate the efficacy and safety of tofacitinib as a treatment for granulomas secondary to filler injection and the possible mechanisms were discussed and summarized. METHODS: This study focuses on three cases of patients who experienced granuloma formation after receiving filler injections and were subsequently treated with tofacitinib. The efficacy and safety of the treatment were evaluated using parameters such as photographs and monitoring for any adverse reactions. In addition, a literature review was conducted to explore the underlying mechanisms and potential effects of tofacitinib. RESULTS: All three cases recovered from swelling and nodules without side effects through the off-label use of oral tofacitinib. Existing data review reveals some approaches for cutaneous granulomatous disorders like inhibiting macrophage activation and downregulation of the JAK-STAT pathway. CONCLUSION: This report emphasizes the effectiveness of JAK inhibitors in treating granulomas caused by filler injections. Recent advancements in understanding the underlying mechanisms of granulomatous reactions have paved the way for JAK inhibitors to be regarded as a promising treatment choice. However, further research is necessary to fully assess the safety and long-term effectiveness of using tofacitinib for granuloma treatment.


Assuntos
Preenchedores Dérmicos , Inibidores de Janus Quinases , Piperidinas , Pirimidinas , Dermatopatias , Humanos , Inibidores de Janus Quinases/uso terapêutico , Janus Quinases , Transdução de Sinais , Fatores de Transcrição STAT , Granuloma/induzido quimicamente , Granuloma/tratamento farmacológico , Dermatopatias/tratamento farmacológico
7.
Opt Express ; 32(7): 11171-11181, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38570971

RESUMO

The spatial and angular Goos-Hänchen shifts (GHSs) and Imbert-Fedorov shifts (IFSs) are theoretically investigated in a modified Kretschmann-Raether configuration consisting of glass prism, J-aggregate cyanine dye, and air. With the excitation of surface excitation polaritons (SEPs), the spatial and angular GHSs and IFSs for the transverse magnetic polarized light are strongly enhanced around the resonant angle of SEP. A highly sensitive gas sensor based on the SEP enhanced GHS (or IFS) is proposed, which exhibits the refractive index sensitivity on the order of 106λ/RIU (or 105λ/RIU) (λ: illumination wavelength; RIU: refractive index unit) for the GHS- (or IFS-) based gas sensor, respectively.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124305, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38657331

RESUMO

A new fluorescent sensor for the determination of lemon yellow was developed based on nitrogen-doped carbon quantum dots (N-CQDs), which were prepared via a hydrothermal method with dried pomelo peel and L-tyrosine. The N-CQDs exhibited the blue fluorescence with a quantum yield of 28 %. The sensing principle of N-CQDs was quenched by lemon yellow via static quenching. The potential interfering substances showed no influence on the detection of lemon yellow. The limit of detection was 0.023 mg/L and lower than that of national standard. Furthermore, the synthesized N-CQDs have been successfully applied to the measurement of lemon yellow in real samples. Hence, the N-CQDs would be a promising sensor in food analysis.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38658361

RESUMO

BACKGROUND: With the increasing occurrence of extreme temperature events due to climate change, the attention has been predominantly focused on the effects of heat waves and cold spells on morbidity and mortality. However, the influence of these temperature extremes on blood parameters has been overlooked. METHODS: We conducted a cohort study involving 2,752 adult blood donors in Tianjin, China, between January 18, 2013, and June 25, 2021. The generalized additive mixed model was used to investigate the effects and lagged effects of heat waves and cold spells on six blood parameters of blood donors, including alanine aminotransferase (ALT), white blood cell count (WBC), red blood cell count (RBC), hemoglobin (HB), hematocrit (HCT), and platelet count (PLT). Subgroup analyses were stratified by sex, age, and BMI. RESULTS: Heat waves and cold spells are associated with changes in blood parameters, particularly HB and PLT. Heat waves increased HB and PLT, while cold spells increased HB and decreased PLT. The effect of heat waves is greater than that of cold spells. The largest effect of heat waves on HB and PLT occurred at lag1 with 2.6 g/L (95% CI: 1.76 to 3.45) and lag7 with 9.71 × 10^9/L (95% CI: 6.26 to 13.17), respectively, while the largest effect of cold spells on HB and PLT occurred at lag0 with 1.02 g/L (95% CI: 0.71 to 1.33) and lag2 with -3.85 × 10^9/L (95% CI: -5.00 to -2.70), respectively. In subgroup analysis, the effect of cold spells on ALT was greater in the 40-49 age group. CONCLUSION: We indicated that heat waves and cold spells can impact hemoglobin and platelet counts in the human body. These findings provide evidence linking heat waves or cold spells to diseases and may reduce health risks caused by extreme temperature events.


Assuntos
Doadores de Sangue , Temperatura Baixa , Temperatura Alta , Humanos , Masculino , Feminino , Doadores de Sangue/estatística & dados numéricos , China/epidemiologia , Adulto , Pessoa de Meia-Idade , Estudos de Coortes , Temperatura Alta/efeitos adversos , Adulto Jovem , Hemoglobinas/análise
11.
Chemistry ; : e202401246, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630894

RESUMO

A thorough understanding of the internal conversion process between excited states is important for designing ideal multiple emissive materials. However, it is hard to experimentally measure both the energy barrier and energy gaps between the excited states of a compound. For a long time, it is dubious if what was measured is the energy gap or energy barrier between two excited states. In this paper, we designed 1-(pyren-2'-yl)-9,12-di(p-tolyl)-o-carborane (2), which shows dual emission in solution. Temperature-dependent fluorescence measurements show that the two emission bands in hexane are corresponding to two different excited states. The ratio of the emission bands is controlled by thermodynamics at higher temperatures and by kinetics at lower temperatures. Thus, the energy barrier and energy gaps between the two excited states of 2 can be experimentally estimated.

12.
Nat Commun ; 15(1): 3181, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609351

RESUMO

The dynamic control of electromagnetic waves is a persistent pursuit in modern industrial development. The state-of-the-art dynamic devices suffer from limitations such as narrow bandwidth, limited modulation range, and expensive features. To address these issues, we fuse origami techniques with metamaterial design to achieve ultra-wideband and large-depth reflection modulation. Through a folding process, our proposed metamaterial achieves over 10-dB modulation depth over 4.96 - 38.8 GHz, with a fractional bandwidth of 155% and tolerance to incident angles and polarizations. Its ultra-wideband and large-depth reflection modulation performance is verified through experiments and analyzed through multipole decomposition theory. To enhance its practical applicability, transparent conductive films are introduced to the metamaterial, achieving high optical transparency (>87%) from visible to near-infrared light while maintaining cost-effectiveness. Benefiting from lightweight, foldability, and low-cost properties, our design shows promise for extensive satellite communication and optical window mobile communication management.

13.
Neuroreport ; 35(7): 476-485, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38597326

RESUMO

The objective of this study is to explore the relationship between the glymphatic system and alterations in the structure and function of the brain in white matter hyperintensity (WMH) patients. MRI data were collected from 27 WMH patients and 23 healthy controls. We calculated the along perivascular space (ALPS) indices, the anterior corner distance of the lateral ventricle, and the width of the third ventricle for each subject. The DPABISurf tool was used to calculate the cortical thickness and cortical area. In addition, data processing assistant for resting-state fMRI was used to calculate regional homogeneity, degree centrality, amplitude low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and voxel-mirrored homotopic connectivity (VMHC). In addition, each WMH patient was evaluated on the Fazekas scale. Finally, the correlation analysis of structural indicators and functional indicators with bilateral ALPS indices was investigated using Spearman correlation analysis. The ALPS indices of WMH patients were lower than those of healthy controls (left: t = -4.949, P < 0.001; right: t = -3.840, P < 0.001). This study found that ALFF, fALFF, regional homogeneity, degree centrality, and VMHC values in some brain regions of WMH patients were alternated (AlphaSim corrected, P < 0.005, cluster size > 26 voxel, rmm value = 5), and the cortical thickness and cortical area of WMH patients showed trend changes (P < 0.01, cluster size > 20 mm2, uncorrected). Interestingly, we found significantly positive correlations between the left ALPS indices and degree centrality values in the superior temporal gyrus (r = 0.494, P = 0.009, P × 5 < 0.05, Bonferroni correction). Our results suggest that glymphatic system impairment is related to the functional centrality of local connections in patients with WMH. This provides a new perspective for understanding the pathological mechanisms of cognitive impairment in the WMH population.


Assuntos
Sistema Glinfático , Substância Branca , Humanos , Sistema Glinfático/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos
14.
Anesthesiology ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38625708

RESUMO

BACKGROUND: Stimulation of the paraventricular thalamus has been found to enhance anesthesia recovery; however, the underlying molecular mechanism by which general anesthetics modulate paraventricular thalamus is unclear. Here, we aimed to test the hypothesis that the sodium leak channel (NALCN) maintains neuronal activity in paraventricular thalamus to resist anesthetic effects of sevoflurane in mice. METHOD: Chemogenetic and optogenetic manipulations, in vivo multiple-channel recordings, and electroencephalogram recordings were used to investigate the role of paraventricular thalamus neuronal activity in sevoflurane anesthesia. Virus-mediated knockdown and/or overexpression was applied to determine how sodium leak channel influenced excitability of paraventricular thalamus glutamatergic neurons under sevoflurane. Viral tracers and local field potentials were used to explore the downstream pathway. RESULTS: Single neuronal spikes in the paraventricular thalamus were suppressed by sevoflurane anesthesia and recovered during emergence. Optogenetic activation of paraventricular thalamus glutamatergic neurons shortened the emergence period from sevoflurane anesthesia, while chemogenetic inhibition had the opposite effect. Knockdown of sodium leak channel in paraventricular thalamus delayed the emergence from sevoflurane anesthesia (recovery time: from 24 ± 14 to 64 ± 19 s, P < 0.001; concentration for recovery of the righting reflex: from 1.13% ± 0.10% to 0.97% ± 0.13%, P < 0.01). As expected, the overexpression of sodium leak channel in the paraventricular thalamus produced the opposite effects. At the circuit level, knockdown of sodium leak channel in the paraventricular thalamus decreased the neuronal activity of the nucleus accumbens, as indicated by the local field potential and decreased single neuronal spikes in the nucleus accumbens. Additionally, the effects of sodium leak channel knockdown in the paraventricular thalamus on sevoflurane actions were reversed by optical stimulation of the nucleus accumbens. CONCLUSIONS: Activity of sodium leak channel maintains the excitability of paraventricular thalamus glutamatergic neurons to resist the anesthetic effects of sevoflurane in mice.

15.
Nat Commun ; 15(1): 3005, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589381

RESUMO

Icosahedral carboranes, C2B10H12, have long been considered to be aromatic but the extent of conjugation between these clusters and their substituents is still being debated. m- and p-Carboranes are compared with m- and p-phenylenes as conjugated bridges in optical functional chromophores with a donor and an acceptor as substituents here. The absorption and fluorescence data for both carboranes from experimental techniques (including femtosecond transient absorption, time-resolved fluorescence and broadband fluorescence upconversion) show that the absorption and emission processes involve strong intramolecular charge transfer between the donor and acceptor substituents via the carborane cluster. From quantum chemical calculations on these carborane systems, the charge transfer process depends on the relative torsional angles of the donor and acceptor groups where an overlap between the two frontier orbitals exists in the bridging carborane cluster.

16.
Thorac Cancer ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38666433

RESUMO

Brain metastases (BM) are common in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) and confer poor prognoses. Zorifertinib (AZD3759), an EGFR-tyrosine kinase inhibitor (TKI) with high blood-brain barrier penetration, has previously demonstrated promising systemic and intracranial antitumor activity in phase 1-3 studies. This is the first report of a patient with EGFR-mutant (exon 21 L858R) NSCLC and symptomatic untreated multiple BM who achieved a long overall survival (OS) of more than 65 months after sequential treatment with zorifertinib and a third-generation EGFR-TKI. This new treatment paradigm offers a new treatment option and deserves further clinical exploration to prolong OS of patients with EGFR-mutant NSCLC and untreated multiple BM.

17.
Front Microbiol ; 15: 1287637, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38426052

RESUMO

Background: Currently, there has been observed a significant alteration in the composition of the gut microbiome (GM) and serum metabolites in patients with psoriatic arthritis (PsA) compared to healthy individuals. However, previous observational studies have shown inconsistent results regarding the alteration of gut microbiota/metabolites. In order to shed light on this matter, we utilized Mendelian randomization to determine the causal effect of GM/metabolites on PsA. Methods: We retrieved summary-level data of GM taxa/metabolites and PsA from publicly available GWAS statistics. Causal relationships between GM/metabolites and PsA were determined using a two-sample MR analysis, with the IVW approach serving as the primary analysis method. To ensure the robustness of our findings, we conducted sensitivity analyses, multivariable MR analysis (MVMR), and additional analysis including replication verification analysis, LDSC regression, and Steiger test analysis. Furthermore, we investigated reverse causality through a reverse MR analysis. Finally, we conducted an analysis of expression quantitative trait loci (eQTLs) involved in the metabolic pathway to explore potential molecular mechanisms of metabolism. Results: Our findings reveal that eight GM taxa and twenty-three serum metabolites are causally related to PsA (P < 0.05). Notably, a higher relative abundance of Family Rikenellaceae (ORIVW: 0.622, 95% CI: 0.438-0.883, FDR = 0.045) and elevated serum levels of X-11538 (ORIVW: 0.442, 95% CI: 0.250-0.781, FDR = 0.046) maintain significant causal associations with a reduced risk of PsA, even after adjusting for multiple testing correction and conducting MVMR analysis. These findings suggest that Family Rikenellaceae and X-11538 may have protective effects against PsA. Our sensitivity analysis and additional analysis revealed no significant horizontal pleiotropy, reverse causality, or heterogeneity. The functional enrichment analysis revealed that the eQTLs examined were primarily associated with glycerolipid metabolism and the expression of key metabolic factors influenced by bacterial infections (Vibrio cholerae and Helicobacter pylori) as well as the mTOR signaling pathway. Conclusion: In conclusion, our study demonstrates that Family Rikenellaceae and X-11538 exhibit a strong and negative causal relationship with PsA. These particular GM taxa and metabolites have the potential to serve as innovative biomarkers, offering valuable insights into the treatment and prevention of PsA. Moreover, bacterial infections and mTOR-mediated activation of metabolic factors may play an important role in this process.

18.
Commun Biol ; 7(1): 262, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438714

RESUMO

Potassium Channel Tetramerization Domain Containing 15 (KCTD15) participates in the carcinogenesis of several solid malignancies; however, its role in colorectal cancer (CRC) remains unclear. Here we find that KCTD15 exhibits lower expression in CRC tissues as compared to para-carcinoma tissues. Tetracycline (tet)-induced overexpression and knockdown of KCTD15 confirms KCTD15 as an anti-proliferative and pro-apoptotic factor in CRC both in vitro and in xenografted tumors. N6-methyladenosine (m6A) is known to affect the expression, stabilization, and degradation of RNAs with this modification. We demonstrate that upregulation of fat mass and obesity-associated protein (FTO), a classical m6A eraser, prevents KCTD15 mRNA degradation in CRC cells. Less KCTD15 RNA is recognized by m6A 'reader' YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2) in FTO-overexpressed cells. Moreover, KCTD15 overexpression decreases protein expression of histone deacetylase 1 (HDAC1) but increases acetylation of critical tumor suppressor p53 at Lys373 and Lys382. Degradation of p53 is delayed in CRC cells post-KCTD15 overexpression. We further show that the regulatory effects of KCTD15 on p53 are HDAC1-dependent. Collectively, we conclude that KCTD15 functions as an anti-growth factor in CRC cells, and its expression is orchestrated by the FTO-YTHDF2 axis. Enhanced p53 protein stabilization may contribute to KCTD15's actions in CRC cells.


Assuntos
Adenina/análogos & derivados , Carcinoma , Neoplasias Colorretais , Humanos , Proteína Supressora de Tumor p53 , Carcinogênese , Neoplasias Colorretais/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Canais de Potássio , Proteínas de Ligação a RNA/genética
19.
BMC Genom Data ; 25(1): 24, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438998

RESUMO

OBJECTIVES: Brasenia is a monotypic genus in the family of Cabombaceae. The only species, B. schreberi, is a macrophyte distributed worldwide. Because it requires good water quality, it is endangered in China and other countries due to the deterioration of aquatic habitats. The young leaves and stems of B. schreberi are covered by thick mucilage, which has high medical value. As an allelopathic aquatic plant, it can also be used in the management of aquatic weeds. Here, we present its assembled and annotated genome to help shed light on medial and allelopathic substrates and facilitate their conservation. DATA DESCRIPTION: Genomic DNA and RNA extracted from B. schreberi leaf tissues were used for whole genome and RNA sequencing using a Nanopore and/or MGI sequencer. The assembly was 1,055,148,839 bp in length, with 92 contigs and an N50 of 22,379,495 bp. The repetitive elements in the assembly were 555,442,205 bp. A completeness assessment of the assembly with BUSCO and compleasm indicated 88.4 and 90.9% completeness in the Eudicots database and 95.4 and 96.6% completeness in the Embryphyta database. Gene annotation revealed 67,747 genes that coded for 73,344 proteins.


Assuntos
Plantas Daninhas , Sementes , Alelopatia , China , Bases de Dados Factuais
20.
Biomark Med ; 18(2): 69-77, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38440878

RESUMO

Background: This study aimed to investigate the clinical value of the red blood cell distribution width (RDW) in severe Mycoplasma pneumoniae pneumonia (MPP). Methods: A total of 185 children with diagnosed severe MPP were included. The patients' case records and laboratory examination data were analyzed retrospectively. The children were grouped into quartiles based on RDW. Results: Univariate analysis revealed that RDW was significantly correlated with the Pediatric Risk of Mortality (PRISM) III score, Sepsis-Related Organ Failure Assessment score, incidence of invasive intubation and 30-day in-hospital mortality. After adjustment for the severity of illness, multivariate analysis revealed that the PRISM III score and RDW were factors independently associated with 30-day in-hospital mortality. Conclusion: This study revealed that RDW could be correlated with the long-term prognosis and severity of severe MPP.


Assuntos
Mycoplasma pneumoniae , Pneumonia , Criança , Humanos , Estudos Retrospectivos , Fatores de Risco , Índices de Eritrócitos , Prognóstico , Eritrócitos , Pneumonia/diagnóstico
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