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2.
BMC Plant Biol ; 24(1): 645, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38972991

ABSTRACT

Melia azedarach is a species of enormous value of pharmaceutical industries. Although the chloroplast genome of M. azedarach has been explored, the information of mitochondrial genome (Mt genome) remains surprisingly limited. In this study, we used a hybrid assembly strategy of BGI short-reads and Nanopore long-reads to assemble the Mt genome of M. azedarach. The Mt genome of M. azedarach is characterized by two circular chromosomes with 350,142 bp and 290,387 bp in length, respectively, which encodes 35 protein-coding genes (PCGs), 23 tRNA genes, and 3 rRNA genes. A pair of direct repeats (R1 and R2) were associated with genome recombination, resulting in two conformations based on the Sanger sequencing and Oxford Nanopore sequencing. Comparative analysis identified 19 homologous fragments between Mt and chloroplast genome, with the longest fragment of 12,142 bp. The phylogenetic analysis based on PCGs were consist with the latest classification of the Angiosperm Phylogeny Group. Notably, a total of 356 potential RNA editing sites were predicted based on 35 PCGs, and the editing events lead to the formation of the stop codon in the rps10 gene and the start codons in the nad4L and atp9 genes, which were verified by PCR amplification and Sanger sequencing. Taken together, the exploration of M. azedarach gap-free Mt genome provides a new insight into the evolution research and complex mitogenome architecture.


Subject(s)
Genome, Mitochondrial , Phylogeny , Recombination, Genetic , Repetitive Sequences, Nucleic Acid/genetics , Genome, Chloroplast , Genome, Plant , RNA Editing
3.
Clin Exp Med ; 24(1): 144, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38960977

ABSTRACT

The primary objective of this study was to assess the incidence, timing, risk factors of fungal infections (FIs) within 3 months after liver transplantation (LT). The secondary objective was to evaluate the impact of FIs on outcomes. Four hundred and ten patients undergoing LT from January 2015 until January 2023 in a tertiary university hospital were included in the present retrospective cohort study to investigate the risk factors of FIs and to assess the impacts of FIs on the prognosis of LT recipients using logistic regression. The incidence of FIs was 12.4% (51/410), and median time from LT to the onset of FIs was 3 days. By univariate analysis, advanced recipient age, prolonged hospital stay prior to LT, high Model for End Stage Liver Disease (MELD) score, use of broad-spectrum antibiotics, and elevated white blood cell (WBC) count, increased operating time, massive blood loss and red blood cell transfusion, elevated alanine aminotransferase on day 1 and creatinine on day 3 after LT, prolonged duration of urethral catheter, prophylactic antifungal therapy, the need for mechanical ventilation and renal replacement therapy were identified as factors of increased post-LT FIs risk. Multivariate logistic regression analysis identified that recipient age ≥ 55 years[OR = 2.669, 95%CI: 1.292-5.513, P = 0.008], MELD score at LT ≥ 22[OR = 2.747, 95%CI: 1.274-5.922, P = 0.010], pre-LT WBC count ≥ 10 × 109/L[OR = 2.522, 95%CI: 1.117-5.692, P = 0.026], intraoperative blood loss ≥ 3000 ml [OR = 2.691, 95%CI: 1.262-5.738, P = 0.010], post-LT duration of urethral catheter > 4 d [OR = 3.202, 95%CI: 1.553-6.602, P = 0.002], and post-LT renal replacement therapy [OR = 5.768, 95%CI: 1.822-18.263, P = 0.003] were independently associated with the development of post-LT FIs. Post-LT prophylactic antifungal therapy ≥ 3 days was associated with a lower risk of the development of FIs [OR = 0.157, 95%CI: 0.073-0.340, P < 0.001]. As for clinical outcomes, FIs had a negative impact on intensive care unit (ICU) length of stay ≥ 7 days than those without FIs [OR = 3.027, 95% CI: 1.558-5.878, P = 0.001] but had no impact on hospital length of stay and 1-month all-cause mortality after LT. FIs are frequent complications after LT and the interval between the onset of FIs and LT was short. Risk factors for post-LT FIs included high MELD score at LT, advanced recipient age, pre-LT WBC count, massive intraoperative blood loss, prolonged post-LT duration of urethral catheter, and the need for post-LT renal replacement therapy. However, post-LT prophylactic antifungal therapy was independently associated with the reduction in the risk of FIs. FIs had a significant negative impact on ICU length of stay.


Subject(s)
Liver Transplantation , Mycoses , Humans , Liver Transplantation/adverse effects , Middle Aged , Male , Female , Retrospective Studies , Risk Factors , Mycoses/epidemiology , Mycoses/prevention & control , Mycoses/etiology , Adult , Incidence , Aged , Postoperative Complications , Prognosis , Tertiary Care Centers , Treatment Outcome , Length of Stay
4.
Br J Hosp Med (Lond) ; 85(7): 1-9, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39078912

ABSTRACT

Aims/Background Patients with chronic rhinosinusitis often have a higher incidence of anxiety and depression. Nevertheless, the impact of specific chronic rhinosinusitis types (chronic anterior/posterior/anterior and posterior rhinosinusitis) on anxiety and depression remains unexplored. Methods From January 2022 to July 2023, we employed various assessment scales to gauge the severity of chronic rhinosinusitis and anxiety and depression among Chinese patients with chronic rhinosinusitis. Statistical analysis involved non-parametric tests and binary logistic regression. Results In total, 123 patients with chronic rhinosinusitis were enrolled. The number of patients with anxiety and depression in the chronic posterior rhinosinusitis and chronic anterior and posterior rhinosinusitis groups (p=0.022), the nasal symptom subdomain scores of the chronic anterior rhinosinusitis and chronic anterior and posterior rhinosinusitis (p=0.011) groups and the chronic posterior rhinosinusitis and chronic anterior and posterior rhinosinusitis (p=0.008) groups, and the Lund-Kennedy score of the three groups (all p < 0.05) were significantly different. Binary logistic regression analysis revealed that chronic rhinosinusitis type (p=0.035) was a risk factor for anxiety and depression. Conclusion Anatomical chronic rhinosinusitis type was a risk factor for anxiety and depression in patients with chronic rhinosinusitis.


Subject(s)
Anxiety , Depression , Rhinitis , Sinusitis , Humans , Sinusitis/psychology , Sinusitis/complications , Rhinitis/psychology , Rhinitis/complications , Male , Chronic Disease , Female , Depression/epidemiology , Middle Aged , Anxiety/epidemiology , Adult , China/epidemiology , Severity of Illness Index , Risk Factors , Aged , Rhinosinusitis
5.
Nat Commun ; 15(1): 6433, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39085266

ABSTRACT

The kink structure in band dispersion usually refers to a certain electron-boson interaction, which is crucial in understanding the pairing in unconventional superconductors. Here we report the evidence of the observation of a kink structure in Fe-based superconductor CsCa2Fe4As4F2 using angle-resolved photoemission spectroscopy. The kink shows an orbital selective and momentum dependent behavior, which is located at 15 meV below Fermi level along the Γ - M direction at the band with dxz orbital character and vanishes when approaching the Γ - X direction, correlated with a slight decrease of the superconducting gap. Most importantly, this kink structure disappears when the superconducting gap closes, indicating that the corresponding bosonic mode (~ 9 ± 1 meV) is closely related to superconductivity. However, the origin of this mode remains unidentified, since it cannot be related to phonons or the spin resonance mode (~15 meV) observed by inelastic neutron scattering. The behavior of this mode is rather unique and challenges our present understanding of the superconducting paring mechanism of the bilayer FeAs-based superconductors.

6.
Heliyon ; 10(12): e33146, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38994066

ABSTRACT

Background: Acne inversa (AI) is a refractory inflammatory skin disease, and TNF-α plays an important role in the pathogenesis of AI. By blocking TNF-α, infliximab (IFX) has been proven to be a promising method. Objectives: To explore the underlying mechanisms of IFX treatment in AI patients. Methods: In this research, we integrated transcriptome sequencing data from the samples of our patients with AI and the GEO database. Ex vivo skin culture of AI patients was conducted to evaluate the efficacy of IFX treatment. Animal studies and cell experiments were used to explore the therapeutic effect and mechanism of IFX treatment. Results: Both TNF-α and NLRP3 inflammasome-related pathways were enriched in skin lesions of AI patients and murine AI models. After IFX treatment, the NLRP3 inflammasome-related pathway was effectively blocked, and the IL-1ß level was normalized in ex vivo AI skin explants and murine AI models. Mechanistically, IFX suppressed the NF-κB signaling pathway to lower the expression of NLRP3 and IL-1ß in keratinocytes. Conclusions: IFX treatment alleviated skin lesions in murine AI models and downregulated NLRP3 and IL-1ß expression levels by inhibiting the NF-κB signaling pathway, which was helpful for understanding the mechanism of IFX therapy.

7.
Nat Commun ; 15(1): 5555, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030177

ABSTRACT

Neurotransmitters are key modulators in neuro-immune circuits and have been linked to tumor progression. Medullary thyroid cancer (MTC), an aggressive neuroendocrine tumor, expresses neurotransmitter calcitonin gene-related peptide (CGRP), is insensitive to chemo- and radiotherapies, and the effectiveness of immunotherapies remains unknown. Thus, a comprehensive analysis of the tumor microenvironment would facilitate effective therapies and provide evidence on CGRP's function outside the nervous system. Here, we compare the single-cell landscape of MTC and papillary thyroid cancer (PTC) and find that expression of CGRP in MTC is associated with dendritic cell (DC) abnormal development characterized by activation of cAMP related pathways and high levels of Kruppel Like Factor 2 (KLF2), correlated with an impaired activity of tumor infiltrating T cells. A CGRP receptor antagonist could offset CGRP detrimental impact on DC development in vitro. Our study provides insights of the MTC immunosuppressive microenvironment, and proposes CGRP receptor as a potential therapeutic target.


Subject(s)
Calcitonin Gene-Related Peptide , Carcinoma, Neuroendocrine , Dendritic Cells , Thyroid Neoplasms , Tumor Microenvironment , Tumor Microenvironment/immunology , Humans , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/immunology , Thyroid Neoplasms/pathology , Calcitonin Gene-Related Peptide/metabolism , Carcinoma, Neuroendocrine/genetics , Carcinoma, Neuroendocrine/metabolism , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/immunology , Dendritic Cells/immunology , Dendritic Cells/metabolism , Thyroid Cancer, Papillary/metabolism , Thyroid Cancer, Papillary/immunology , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/pathology , Receptors, Calcitonin Gene-Related Peptide/metabolism , Cyclic AMP/metabolism , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Neurotransmitter Agents/metabolism , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Calcitonin Gene-Related Peptide Receptor Antagonists/pharmacology , Single-Cell Analysis
8.
iScience ; 27(6): 109990, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38840838

ABSTRACT

The abnormal reproduction of algae in water worldwide is prominent in the context of human interference and global climate change. This study first thoroughly analyzed the effects of physical factors, such as light, temperature, hydrodynamics, and operational strategies, on algal growth and their mechanisms. Physical control techniques are safe and have great potential for preventing abnormal algal blooms in the absence of chemical reagents. The focus was on the principles and possible engineering applications of physical shading, ultrasound, micro-current, and ultraviolet (UV) technologies, in controlling abnormal algal reproduction. Physical shading can inhibit or weaken photosynthesis in algae, thereby inhibiting their growth. Ultrasound mainly affects the physiological and biochemical activities of cells by destroying the cell walls, air cells, and active enzymes. Micro-currents destroy the algal cell structure through direct and indirect oxidation, leading to algal cell death. UV irradiation can damage DNA, causing organisms to be unable to reproduce or algal cells to die directly. This article comprehensively summarizes and analyzes the advantages of physical prevention and control technologies for the abnormal reproduction of algae, providing a scientific basis for future research. In the future, attempts will be made toward appropriately and comprehensively utilizing various physical technologies to control algal blooms. The establishment of an intelligent, comprehensive physical prevention and control system to achieve environmentally friendly, economical, and effective physical prevention and control of algae, such as the South-to-North Water Diversion Project in China, is of great importance for specific waters.

9.
J Infect ; 89(2): 106190, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38834107

ABSTRACT

OBJECTIVES: This study aimed to determine the association of early use of oral antiviral drugs (including nirmatrelvir-ritonavir and molnupiravir) with the risk of post COVID-19 condition (PCC) and compare the possible efficacy of nirmatrelvir-ritonavir and molnupiravir. METHODS: PubMed, Web of Science, Embase, Cochrane, MedRxiv, and Psycinfo were searched from inception until November 1, 2023. We included studies that assessed the effect of oral antiviral drugs on the incidence of PCC. Pairwise and network meta-analyses were conducted using a random-effects model. Risk ratios (RRs) for oral antiviral drugs were calculated with a confidence interval (CI). RESULTS: Nine observational studies containing 866,066 patients were included. Nirmatrelvir-ritonavir and molnupiravir were evaluated in eight and two studies respectively, with both drugs evaluated in one study. Pair-wise meta-analysis showed that early oral antiviral drugs reduced PCC risk (RR 0.77, 95% CI 0.68-0.88). Network meta-analysis showed that nirmatrelvir-ritonavir may perform better than molnupiravir (surface under the cumulative ranking curve: 95.5% vs. 31.6%) at reducing PCC risk. CONCLUSIONS: Early use of oral antiviral drugs may potentially protect against developing PCC in non-hospitalized patients with COVID-19. These findings support the standardized administration of oral antiviral drugs in patients during the acute phase of COVID-19 according to the guidelines.


Subject(s)
Antiviral Agents , COVID-19 Drug Treatment , COVID-19 , Network Meta-Analysis , Ritonavir , SARS-CoV-2 , Humans , Antiviral Agents/therapeutic use , Antiviral Agents/administration & dosage , Ritonavir/therapeutic use , Ritonavir/administration & dosage , Administration, Oral , COVID-19/epidemiology , Drug Combinations , Hydroxylamines/therapeutic use , Hydroxylamines/administration & dosage , Post-Acute COVID-19 Syndrome , Lactams , Cytidine/analogs & derivatives , Nitriles , Proline , Leucine
10.
Int Immunopharmacol ; 138: 112547, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-38943969

ABSTRACT

Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases, and the 5-year survival rate of patients remains unsatisfactory. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that are considered essential posttranscriptional regulators of tumorigenesis, including NSCLC. In this study, we aimed to investigate the biological role of miR-3074-5p in NSCLC cells and the underlying molecular mechanisms. We showed that miR-3074-5p expression was decreased in human NSCLC specimens and cell lines. Moreover, miR-3074-5p overexpression inhibited cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest. In addition, miR-3074-5p overexpression not only suppressed tumor growth but also enhanced the antitumor effect of paclitaxel (PTX) on NSCLC cells in vitro and in vivo. A transcriptome sequencing assay revealed genes that were differentially expressed after miR-3074-5p overexpression, and among the genes whose expression levels were most significantly decreased, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) was a target of miR-3074-5p. The regulatory effect of miR-3074-5p on YWHAZ expression was verified by Western blotting and dual-luciferase reporter assays. The inhibition of A549 cell growth, migration and invasion was reversed by YWHAZ overexpression. Furthermore, we showed that PTX stimulated the expression of the YWHAZ and Hsp27 proteins and promoted the phosphorylation of Hsp27 (at S15 and S78). YWHAZ was confirmed to interact with Hsp27 in A549 cells, and downregulating YWHAZ expression promoted the degradation of the Hsp27 protein. Taken together, these results suggest that the miR-3074-5p/YWHAZ/Hsp27 axis may be a novel therapeutic target for NSCLC treatment.


Subject(s)
14-3-3 Proteins , Carcinoma, Non-Small-Cell Lung , Cell Proliferation , Gene Expression Regulation, Neoplastic , HSP27 Heat-Shock Proteins , Lung Neoplasms , MicroRNAs , Paclitaxel , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/drug therapy , 14-3-3 Proteins/metabolism , 14-3-3 Proteins/genetics , Paclitaxel/pharmacology , Paclitaxel/therapeutic use , Animals , Gene Expression Regulation, Neoplastic/drug effects , Cell Proliferation/drug effects , HSP27 Heat-Shock Proteins/metabolism , HSP27 Heat-Shock Proteins/genetics , Cell Movement/drug effects , Cell Line, Tumor , Mice, Nude , Apoptosis/drug effects , Male , Mice , Heat-Shock Proteins/metabolism , Heat-Shock Proteins/genetics , Mice, Inbred BALB C , Female , Molecular Chaperones/metabolism , A549 Cells , Signal Transduction
11.
Ecotoxicol Environ Saf ; 280: 116476, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38820822

ABSTRACT

Rural waste accumulation leads to heavy metal soil pollution, impacting microbial communities. However, knowledge gaps exist regarding the distribution and occurrence patterns of bacterial communities in multi-metal contaminated soil profiles. In this study, high-throughput 16 S rRNA gene sequencing technology was used to explore the response of soil bacterial communities to various heavy metal pollution in rural simple waste dumps in karst areas of Southwest China. The study selected three habitats in the center, edge, and uncontaminated areas of the waste dump to evaluate the main factors driving the change in bacterial community composition. Pollution indices reveal severe contamination across all elements, except for moderately polluted lead (Pb); contamination severity ranks as follows: Mn > Cd > Zn > Cr > Sb > V > Cu > As > Pb. Proteobacteria, Actinobacteria, Chloroflexi, and Acidobacteriota predominate, collectively constituting over 60% of the relative abundance. Analysis of Chao and Shannon indices demonstrated that the waste dump center boasted the greatest bacterial richness and diversity. Correlation data indicated a predominant synergistic interaction among the landfill's bacterial community, with a higher number of positive associations (76.4%) compared to negative ones (26.3%). Network complexity was minimal at the dump's edge. RDA analysis showed that Pb(explained:46%) and Mn(explained:21%) were the key factors causing the difference in bacterial community composition in the edge area of the waste dump, and AK(explained:42.1%) and Cd(explained:35.2%) were the key factors in the center of the waste dump. This study provides important information for understanding the distribution patterns, co-occurrence networks, and environmental response mechanisms of bacterial communities in landfill soils under heavy metal stress, which helps guide the formulation of rural waste treatment and soil remediation strategies.


Subject(s)
Metals, Heavy , Soil Microbiology , Soil Pollutants , Soil , Metals, Heavy/analysis , Metals, Heavy/toxicity , Soil Pollutants/analysis , Soil Pollutants/toxicity , China , Soil/chemistry , Bacteria/drug effects , Bacteria/genetics , Bacteria/classification , RNA, Ribosomal, 16S , Waste Disposal Facilities , Environmental Monitoring , Proteobacteria , Actinobacteria/genetics , Microbiota/drug effects , Chloroflexi/drug effects , Chloroflexi/genetics
12.
Mol Biol Evol ; 41(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38768215

ABSTRACT

High mountains harbor a considerable proportion of biodiversity, but we know little about how diverse plants adapt to the harsh environment. Here we finished a high-quality genome assembly for Dasiphora fruticosa, an ecologically important plant distributed in the Qinghai-Tibetan Plateau and lowland of the Northern Hemisphere, and resequenced 592 natural individuals to address how this horticulture plant adapts to highland. Demographic analysis revealed D. fruticosa underwent a bottleneck after Naynayxungla Glaciation. Selective sweep analysis of two pairs of lowland and highland populations identified 63 shared genes related to cell wall organization or biogenesis, cellular component organization, and dwarfism, suggesting parallel adaptation to highland habitats. Most importantly, we found that stronger purging of estimated genetic load due to inbreeding in highland populations apparently contributed to their adaptation to the highest mountain. Our results revealed how plants could tolerate the extreme plateau, which could provide potential insights for species conservation and crop breeding.


Subject(s)
Genome, Plant , Selection, Genetic , Adaptation, Physiological/genetics , Altitude
14.
BMC Womens Health ; 24(1): 239, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38616274

ABSTRACT

OBJECTIVE: To evaluate the surface electromyography (sEMG) of pelvic floor muscles (PFMs), compare between vaginal birth and cesarean section and correlate with maternity and obstetrics characteristics in primiparous 6-8 weeks postpartum. METHODS: PFMs surface electromyography screening data of primiparous postpartum women in our hospital at 6-8 weeks postpartum from 2018 to 2021 were selected and analyzed. The study collected data on delivery activities of 543 postpartum women totally. RESULTS: In general, the abnormal incidence of pelvic floor electromyography in postpartum women mainly occurred in slow muscle (type I fiber) stage and endurance testing stage. Compared to vaginal birth postpartum women, the incidence of abnormal pelvic floor electromyography in cesarean section postpartum women is lower. There were statistical differences in measurement values of pelvic floor electromyography in several different stages between cesarean section and vaginal birth (P < 0.005). Regarding the influence on pelvic floor electromyography, there were more influencing factors on vaginal birth postpartum women including age, height, weight, weight gain during pregnancy, gestational week, and first and second stage of labor than on cesarean section postpartum women whose influencing factors included age, weight gain during pregnancy, and newborn weight. CONCLUSION: Effects on surface electromyography (sEMG) of pelvic floor muscles (PFMs) at 6-8 weeks postpartum differed based on the different modes of delivery. The high-risk obstetric factors closely related to abnormal surface electromyography (sEMG) of pelvic floor muscles (PFMs) were maternal age, height, weight, and second stage of labor.


Subject(s)
Cesarean Section , Pelvic Floor , Pregnancy , Infant, Newborn , Female , Humans , Cross-Sectional Studies , Electromyography , Postpartum Period , Weight Gain
15.
Toxics ; 12(4)2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38668473

ABSTRACT

The characterization of dissolved organic matter (DOM) is important for better understanding of the migration and transformation mechanisms of DOM in water bodies and its interaction with other contaminants. In this work, fluorescence characteristics and molecular compositions of the DOM samples collected from the mainstream, tributary, and sewage outfall of the Inner Mongolia section of the Yellow River (IMYR) were determined by using fluorescence spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). In addition, concentrations of potentially toxic elements (PTEs) in the relevant surface water and their potential relationships with DOM were investigated. The results showed that the abundance of tyrosine-like components increased significantly in downstream waters impacted by outfall effluents and was negatively correlated with the humification index (HIX). Compared to the mainstream, outfall and tributaries have a high number of molecular formulas and a higher proportion of CHOS molecular formulas. In particular, the O5S class has a relative intensity of 41.6% and the O5-7S class has more than 70%. Thirty-eight PTEs were measured in the surface water samples, and 12 found above their detective levels at all sampling sites. Protein-like components are positively correlated with Cu, which is likely indicating the source of Cu in the aquatic environment of the IMYR. Our results demonstrated that urban wastewater discharges significantly alter characteristics and compositions of DOM in the mainstream of IMYR with strongly anthropogenic features. These results and conclusions are important for understanding the role and sources of DOM in the Yellow River aquatic environment.

16.
J Nanobiotechnology ; 22(1): 131, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38532389

ABSTRACT

Effective intracellular DNA transfection is imperative for cell-based therapy and gene therapy. Conventional gene transfection methods, including biochemical carriers, physical electroporation and microinjection, face challenges such as cell type dependency, low efficiency, safety concerns, and technical complexity. Nanoneedle arrays have emerged as a promising avenue for improving cellular nucleic acid delivery through direct penetration of the cell membrane, bypassing endocytosis and endosome escape processes. Nanostraws (NS), characterized by their hollow tubular structure, offer the advantage of flexible solution delivery compared to solid nanoneedles. However, NS struggle to stably self-penetrate the cell membrane, resulting in limited delivery efficiency. Coupling with extra physiochemical perforation strategies is a viable approach to improve their performance. This study systematically compared the efficiency of NS coupled with polyethylenimine (PEI) chemical modification, mechanical force, photothermal effect, and electric field on cell membrane perforation and DNA transfection. The results indicate that coupling NS with PEI modification, mechanical force, photothermal effects provide limited enhancement effects. In contrast, NS-electric field coupling significantly improves intracellular DNA transfection efficiency. This work demonstrates that NS serve as a versatile platform capable of integrating various physicochemical strategies, while electric field coupling stands out as a form worthy of primary consideration for efficient DNA transfection.


Subject(s)
DNA , Electroporation , Transfection , Cell Membrane , Genetic Therapy , Polyethyleneimine/chemistry
17.
Biomed Pharmacother ; 173: 116231, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38484561

ABSTRACT

Since December 2019, the infection caused by Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) has posed an enormous threat to human health security worldwide. Constant mutation of viral genome and varying therapeutic responses of patients infected with this virus prompted efforts to uncover more novel regulators in the pathogenesis. The involvement of N6-methyladenosine, a modified form of RNA, plays a crucial role in viral replication, viral pathogenicity, and intricate signaling pathways connected with immune responses. This review discusses research advances revealing the regulation of the life cycle of SARS-CoV-2 and antiviral responses of host cells by RNA m6A modification, highlights the biological functions of N6-methyladenosine components in SARS-CoV-2 infection and virus-host interactions, and outlines current challenges and future directions for exploring the potential clinical value of m6A modification in COVID-19.


Subject(s)
COVID-19 , Humans , Host Microbial Interactions , SARS-CoV-2 , RNA
18.
Neuroscience ; 542: 21-32, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38340785

ABSTRACT

Neuroinflammation is an early event of brain injury after subarachnoid hemorrhage (SAH). Whether the macrophage mediators in resolving inflammation 1 (MaR1) is involved in SAH pathogenesis is unknown. In this study, 205 male Sprague-Dawley rats were subjected to SAH via endovascular perforation in the experimental and control groups. MaR1 was dosed intranasally at 1 h after SAH, with LGR6 siRNA and KG-501, GSK-J4 administered to determine the signaling pathway. Neurobehavioral, histological and biochemical data were obtained from the animal groups with designated treatments. The results showed: (i) The leucine-rich repeat containing G protein-coupled receptor 6 (LGR6) was decreased after SAH and reached to the lowest level at 24 h after SAH. Jumonji d3 (JMJD3) protein levels tended to increase and peaked at 24 h after SAH. LGR6 and JMJD3 expression were co-localized with microglia. (ii) MaR1 administration mitigated short-term neurological deficits, brain edema and long-term neurobehavioral performance after SAH, and attenuated microglial activation and neutrophil infiltration. (iii) Knockdown of LGR6, inhibition of CREB phosphorylation or JMJD3 activity abolished the anti-neuroinflammatory effect of MaR1 on the expression of CREB, CBP, JMJD3, IRF4, IRF5, IL-1ß, IL-6 and IL-10, thus prevented microglial activation and neutrophil infiltration. Together, the results show that MaR1 can activate LGR6 and affect CREB/JMJD3/IRF4 signaling to attenuate neuroinflammation after SAH, pointing to a potential pharmacological utility in this disorder.


Subject(s)
Docosahexaenoic Acids , Neuroinflammatory Diseases , Subarachnoid Hemorrhage , Rats , Male , Animals , Rats, Sprague-Dawley , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/drug therapy , Subarachnoid Hemorrhage/metabolism , Signal Transduction
19.
Front Cell Infect Microbiol ; 14: 1289231, 2024.
Article in English | MEDLINE | ID: mdl-38318165

ABSTRACT

Background: Pulmonary trichomoniasis is considered a neglected disease due to failures in recognizing it, stemming from insensitive microbial methods and a lack of specific clinical features. This study aims to analyze the clinical implications of trichomonads detected in bronchoalveolar lavage fluid (BALF) by metagenomic next-generation sequencing (mNGS). Methods: This multicenter retrospective study included patients diagnosed with pneumonia, admitted to three tertiary hospitals in China from July 2018 to September 2022, with trichomonads detected in BALF through mNGS. The analysis covered demographics, comorbidities, symptoms, laboratory findings, mNGS results, clinical treatment, and outcomes of these patients. Results: A total of 17 patients were enrolled, comprising 14 males and 3 females. Trichomonas tenax and Trichomonas vaginalis were detected by mNGS in BALF samples of 15 and 2 patients, respectively. Patients were categorized into two groups based on the presence of risk factors for trichomonad infection, including immunocompromised conditions, uncontrolled diabetes mellitus, oral/periodontal diseases, and aspiration. Among 11 patients with risk factors (Case 1-11), 4 received nitromidazoles as part of comprehensive treatment, achieving a 100% treatment success rate. The remaining 7 patients, who did not receive nitromidazoles, had only one achieving relief after broad-spectrum antimicrobial therapy, resulting in a 14.3% treatment success rate. For the 6 patients without any risk factors for trichomonad infection (Case 12-17), none received nitromidazoles during hospitalization. However, 4 out of these 6 patients (66.7%) eventually recovered. Conclusion: mNGS proves to be an efficient tool for detecting trichomonads in BALF samples. Comprehensive analysis of clinical features and laboratory indicators is essential to distinguish between infection and colonization of trichomonads. Pulmonary trichomoniasis should not be overlooked when trichomonads are detected in BALF from patients with risk factors.


Subject(s)
High-Throughput Nucleotide Sequencing , Trichomonas Infections , Female , Male , Humans , Retrospective Studies , Bronchoalveolar Lavage Fluid , Risk Factors , Metagenomics , Trichomonas Infections/diagnosis , Sensitivity and Specificity
20.
Acta Pharmacol Sin ; 45(6): 1130-1141, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38195693

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most common malignancy, presenting a formidable challenge to the medical community owing to its intricate pathogenic mechanisms. Although current prevention, surveillance, early detection, diagnosis, and treatment have achieved some success in preventing HCC and controlling overall disease mortality, the imperative to explore novel treatment modalities for HCC remains increasingly urgent. Epigenetic modification has emerged as pivotal factors in the etiology of cancer. Among these, RNA N6-methyladenosine (m6A) modification stands out as one of the most prevalent, abundant, and evolutionarily conserved post-transcriptional alterations in eukaryotes. The literature underscores that the dynamic and reversible nature of m6A modifications orchestrates the intricate regulation of gene expression, thereby exerting a profound influence on cell destinies. Increasing evidence has substantiated conspicuous fluctuations in m6A modification levels throughout the progression of HCC. The deliberate modulation of m6A modification levels through molecular biology and pharmacological interventions has been demonstrated to exert a discernible impact on the pathogenesis of HCC. In this review, we elucidate the multifaceted biological functions of m6A modifications in HCC, and concurrently advancing novel therapeutic strategies for the management of this malignancy.


Subject(s)
Adenosine , Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Adenosine/analogs & derivatives , Adenosine/metabolism , Animals , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , RNA/metabolism , RNA/genetics
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