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1.
Pharmacol Res ; : 107266, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38878918

RESUMO

Cerebral ischemia-reperfusion injury (I/RI) is one of the principal pathogenic factors in the poor prognosis of ischemic stroke, for which current therapeutic options to enhance neurological recovery are notably insufficient. Dental pulp stem cell-derived extracellular vesicles (DPSC-EVs) have promising prospects in stroke treatment and the specific underlying mechanisms have yet to be fully elucidated. The present study observed that DPSC-EVs ameliorated the degree of cerebral edema and infarct volume by reducing the apoptosis of neurons. Furthermore, the miRNA sequencing and functional enrichment analysis identified that miR-877-3p as a key component in DPSC-EVs, contributing to neuroprotection and anti-apoptotic effects. Following target prediction and dual-luciferase assay indicated that miR-877-3p interacted with Bcl-2-associated transcription factor (Bclaf1) to play a function. The miR-877-3p inhibitor or Bclaf1 overexpression reversed the neuroprotective effects of DPSC-EVs. The findings reveal a novel therapeutic pathway where miR-877-3p, transferred via DPSC-EVs, confers neuroprotection against cerebral I/RI, highlighting its potential in promoting neuronal survival and recovery post-ischemia.

2.
Animals (Basel) ; 14(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38891645

RESUMO

Although the pencilfish is a globally popular economic fish in the aquarium market, its taxonomic classification could be further refined. In order to understand the taxonomy of species of the genus Nannostomus (Characiformes, Lebiasinidae) and their phylogenetic position within the order Characiformes, in this study, we characterized mitochondrial genomes (mitogenomes) from four Nannostomus species for the first time. The four mitogenomes exhibited the typical circular structure, with overall sizes varying from 16,661 bp to 16,690 bp. They contained 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and 1 control region (CR). Nucleotide composition analysis suggested that the mitochondrial sequences were biased toward A and T. Bayesian inference and maximum likelihood analyses based on PCGs support the family Lebiasinidae classification, described using four Nannostomus species, clustering together with Lebiasina multimaculata from the same family. The results of this study support the current taxonomic classification of the family Lebiasinidae. Phylogenetic analysis also suggested that gene rearrangement would not significantly impact the phylogenetic relationships within the order Characiformes. These results might provide new data regarding the phylogeny and classification of the order Characiformes, thus providing a theoretical basis for the economic development of aquarium fish markets.

3.
Genomics ; 116(5): 110881, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906513

RESUMO

Alkaloids are the main medicinal components in Houttuynia cordata. In this study, two accessions 6# and 7# of H. cordata underwent thorough metabolomic analyses to identify and quantify alkaloid phytometabolites. It turned out that the alkaloid types were largely similar between 6# and 7#, and the identified 81 alkaloids could be divided into nine structural classes. However, the content of alkaloids in the two accessions was quite different. According to transcriptome data, a total of 114 differentially expressed genes related to alkaloid metabolism were screened. The alkaloid synthesis pathway of the two varieties was mainly different in the isoquinoline alkaloid biosynthesis and indole alkaloid biosynthesis; four genes A22110063c_transcript_59323, A22110063c_transcript_60118, A22110063c_transcript_51672 and A22110063c_transcript_48784 were highly expressed in 7#, which could be key candidate genes of alkaloid metabolism and warrant further analysis. These results provide a reference for the medicinal application of H. cordata and breeding alkaloid rich varieties.

4.
Front Microbiol ; 15: 1404558, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38841061

RESUMO

Swine leukocyte antigen (SLA) class I molecule-restricted T-cell epitopes, which induce cytotoxic T lymphocyte (CTL) responses, play a critical role in the clearance of porcine reproductive and respiratory syndrome virus (PRRSV) and the development of efficient protective vaccines. The SLA-1*04:01:01, SLA-2*04:01, and SLA-3*04:01 alleles, assigned the Hp-4.0 haplotype, are highly prevalent and usually present in all pig breeds. However, the SLA Hp-4.0 haplotype-restricted CTL epitopes in the structural membrane (M) protein of PRRSV are still unknown. In this study, we predicted 27 possible 9-mer epitope peptides in M protein with high binding scores for SLA-1*04:01:01 using CTL epitope prediction tools. In total, 45 SLA class I complexes, comprising the predicted peptide, extracellular region of the SLA-I molecules, and ß2-microglobulin, were constructed in vitro to detect the specific binding of these peptides to SLA-1*04:01:01 (27 complexes), SLA-2*04:01 (9 complexes), and SLA-3*04:01 (9 complexes), respectively. Our results showed that the M27 (T91WKFITSRC), M39 (N130HAFVVRRP), and M49 (G158RKAVKQGV) peptides bind specifically to SLA-1*04:01:01, SLA-2*04:01, and SLA-3*04:01, respectively. Subsequently, using peripheral blood mononuclear cells (PBMCs) isolated from the homozygous Hp-4.0 and Hp-26.0 haplotype piglets vaccinated with commercial PRRSV HuN4-F112 strain, we determined the capacities of these 27 potential peptides to stimulate their proliferation with a Cell Counting Kit-8 and their secretion and expression of interferon gamma (IFN-γ) with an ELISpot assay and real-time qPCR, respectively. The immunological activities of M27, M39, and M49 were therefore confirmed when they efficiently induced PBMC proliferation and IFN-γ secretion in PBMCs from piglets with the prevalent SLA Hp-4.0 haplotype. The amino acid sequence alignment revealed that M27, M39, and M49 are highly conserved among 248 genotype II PRRSV strains collected between 1998 and 2019. These findings contribute to the understanding of the mechanisms of cell-mediated immune responses to PRRSV. Our study also provides a novel strategy for identifying and confirming potential SLA haplotype-restricted CTL epitopes that could be used to develop novel peptide-based vaccines against swine diseases.

5.
Int J Surg ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913424

RESUMO

Surgical resection is essential for treating solid tumors, with success largely dependent on the complete excision of neoplastic cells. However, neurosurgical procedures must delicately balance tumor removal with the preservation of surrounding tissue. Achieving clear margins is particularly challenging in cases like glioblastoma due to the limitations of traditional white light visualization. These limitations often result in incomplete resections, leading to frequent recurrences, or excessive resection that harms vital neural structures, causing iatrogenic nerve damage which can lead to sensory and functional deficits. Current statistics reveal a 90% recurrence rate for malignant gliomas. Similarly, an 8% incidence of iatrogenic nerve trauma contributes to an estimated 25 million cases of peripheral nerve injury globally each year. These figures underscore the urgent need for improved intraoperative techniques for lesion margin and nerve identification and visualization. Recent advances in neurosurgical imaging, such as fluorescence-guided surgery (FGS), have begun to address these challenges. Fluorescent agents used in FGS illuminate target tissues, although not all do so selectively. Despite the promising results of agents such as 5-aminolevulinic acid and indocyanine green, their applications are mainly limited by issues of sensitivity and specificity. Furthermore, these agents do not effectively address the need for precise nerve visualization. Nerve Peptide 41, a novel systemically administered fluorescent nerve-targeted probe, shows promise in filling this gap. This review assesses the major fluorescent imaging modalities in neurosurgery, highlighting each of their benefits, limitations, and potential.

6.
J Zhejiang Univ Sci B ; 25(6): 499-512, 2024 Jun 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38910495

RESUMO

Artificial vascular graft (AVG) fistula is widely used for hemodialysis treatment in patients with renal failure. However, it has poor elasticity and compliance, leading to stenosis and thrombosis. The ideal artificial blood vessel for dialysis should replicate the structure and components of a real artery, which is primarily maintained by collagen in the extracellular matrix (ECM) of arterial cells. Studies have revealed that in hepatitis B virus (HBV)-induced liver fibrosis, hepatic stellate cells (HSCs) become hyperactive and produce excessive ECM fibers. Furthermore, mechanical stimulation can encourage ECM secretion and remodeling of a fiber structure. Based on the above factors, we transfected HSCs with the hepatitis B viral X (HBX) gene for simulating the process of HBV infection. Subsequently, these HBX-HSCs were implanted into a polycaprolactone-polyurethane (PCL-PU) bilayer scaffold in which the inner layer is dense and the outer layer consists of pores, which was mechanically stimulated to promote the secretion of collagen nanofiber from the HBX-HSCs and to facilitate crosslinking with the scaffold. We obtained an ECM-PCL-PU composite bionic blood vessel that could act as access for dialysis after decellularization. Then, the vessel scaffold was implanted into a rabbit's neck arteriovenous fistula model. It exhibited strong tensile strength and smooth blood flow and formed autologous blood vessels in the rabbit's body. Our study demonstrates the use of human cells to create biomimetic dialysis blood vessels, providing a novel approach for creating clinical vascular access for dialysis.


Assuntos
Células Estreladas do Fígado , Poliésteres , Diálise Renal , Coelhos , Animais , Poliésteres/química , Proteínas Virais Reguladoras e Acessórias , Alicerces Teciduais , Transfecção , Biônica , Poliuretanos , Prótese Vascular , Matriz Extracelular/metabolismo , Humanos , Vírus da Hepatite B/genética , Colágeno , Engenharia Tecidual/métodos , Transativadores
7.
Transl Vis Sci Technol ; 13(5): 8, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38739084

RESUMO

Purpose: This study aimed to evaluate the ocular characteristics associated with spontaneously high myopia in adult nonhuman primates (NHPs). Methods: A total of 537 eyes of 277 macaques with an average age of 18.53 ± 3.01 years (range = 5-26 years), raised in a controlled environment, were included. We measured ocular parameters, including spherical equivalent (SE), axial length (AXL), and intraocular pressure. The 45-degree fundus images centered on the macula and the disc assessed the fundus tessellation and parapapillary atrophy (PPA). Additionally, optical coherence tomography (OCT) was used to measure the thickness of the retinal nerve fiber layer (RNFL). Results: The mean SE was -1.58 ± 3.71 diopters (D). The mean AXL was 18.76 ± 0.86 mm. The prevalence rate of high myopia was 17.7%. As myopia aggravated, the AXL increased (r = -0.498, P < 0.001). Compared with non-high myopia, highly myopic eyes had a greater AXL (P < 0.001), less RNFL thickness (P = 0.004), a higher incidence of PPA (P < 0.001), and elevated grades of fundus tessellation (P < 0.001). The binary logistic regression was performed, which showed PPA (odds ratio [OR] = 4.924, 95% confidence interval [CI] = 2.375-10.207, P < 0.001) and higher grades of fundus tessellation (OR = 1.865, 95% CI = 1.474-2.361, P < 0.001) were independent risk characteristics for high myopia. Conclusions: In NHPs, a higher grade of fundus tessellation and PPA were significant biomarkers of high myopia. Translational Relevance: The study demonstrates adult NHPs raised in conditioned rooms have a similar prevalence and highly consistent fundus changes with human beings, which strengthens the foundation for utilizing macaques as an animal model in high myopic studies.


Assuntos
Fundo de Olho , Tomografia de Coerência Óptica , Animais , Masculino , Feminino , Modelos Animais de Doenças , Disco Óptico/patologia , Disco Óptico/diagnóstico por imagem , Atrofia Óptica/patologia , Atrofia Óptica/epidemiologia , Pressão Intraocular/fisiologia , Miopia Degenerativa/patologia , Miopia Degenerativa/epidemiologia , Fibras Nervosas/patologia , Comprimento Axial do Olho/patologia , Células Ganglionares da Retina/patologia , Miopia/patologia , Miopia/epidemiologia , Miopia/veterinária
8.
Front Endocrinol (Lausanne) ; 15: 1413519, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706695

RESUMO

[This corrects the article DOI: 10.3389/fendo.2024.1294638.].

9.
10.
J Clin Invest ; 134(8)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38618952

RESUMO

N6-Methyladenosine (m6A) is the most abundant posttranscriptional modification, and its contribution to cancer evolution has recently been appreciated. Renal cancer is the most common adult genitourinary cancer, approximately 85% of which is accounted for by the clear cell renal cell carcinoma (ccRCC) subtype characterized by VHL loss. However, it is unclear whether VHL loss in ccRCC affects m6A patterns. In this study, we demonstrate that VHL binds and promotes METTL3/METTL14 complex formation while VHL depletion suppresses m6A modification, which is distinctive from its canonical E3 ligase role. m6A RNA immunoprecipitation sequencing (RIP-Seq) coupled with RNA-Seq allows us to identify a selection of genes whose expression may be regulated by VHL-m6A signaling. Specifically, PIK3R3 is identified to be a critical gene whose mRNA stability is regulated by VHL in a m6A-dependent but HIF-independent manner. Functionally, PIK3R3 depletion promotes renal cancer cell growth and orthotopic tumor growth while its overexpression leads to decreased tumorigenesis. Mechanistically, the VHL-m6A-regulated PIK3R3 suppresses tumor growth by restraining PI3K/AKT activity. Taken together, we propose a mechanism by which VHL regulates m6A through modulation of METTL3/METTL14 complex formation, thereby promoting PIK3R3 mRNA stability and protein levels that are critical for regulating ccRCC tumorigenesis.


Assuntos
Adenina , Carcinoma de Células Renais , Neoplasias Renais , Adulto , Humanos , Carcinogênese/genética , Carcinoma de Células Renais/genética , Transformação Celular Neoplásica , Expressão Gênica , Neoplasias Renais/genética , Metiltransferases/genética , Fosfatidilinositol 3-Quinases/genética
11.
Acta Neuropathol Commun ; 12(1): 61, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637883

RESUMO

We aimed to identify the druggable cell-intrinsic vulnerabilities and target-based drug therapies for PitNETs using the high-throughput drug screening (HTS) and genomic sequencing methods. We examined 9 patient-derived PitNET primary cells in HTS. Based on the screening results, the potential target genes were analyzed with genomic sequencing from a total of 180 PitNETs. We identified and verified one of the most potentially effective drugs, which targeted the Histone deacetylases (HDACs) both in in vitro and in vivo PitNET models. Further RNA sequencing revealed underlying molecular mechanisms following treatment with the representative HDACs inhibitor, Panobinostat. The HTS generated a total of 20,736 single-agent dose responses which were enriched among multiple inhibitors for various oncogenic targets, including HDACs, PI3K, mTOR, and proteasome. Among these drugs, HDAC inhibitors (HDACIs) were, on average, the most potent drug class. Further studies using in vitro, in vivo, and isolated PitNET primary cell models validated HDACIs, especially Panobinostat, as a promising therapeutic agent. Transcriptional surveys revealed substantial alterations to the Nrf2 signaling following Panobinostat treatment. Moreover, Nrf2 is highly expressed in PitNETs. The combination of Panobinostat and Nrf2 inhibitor ML385 had a synergistic effect on PitNET suppression. The current study revealed a class of effective anti-PitNET drugs, HDACIs, based on the HTS and genomic sequencing. One of the representative compounds, Panobinostat, may be a potential drug for PitNET treatment via Nrf2-mediated redox modulation. Combination of Panobinostat and ML385 further enhance the effectiveness for PitNET treatment.


Assuntos
Tumores Neuroendócrinos , Neoplasias Hipofisárias , Humanos , Panobinostat/farmacologia , Panobinostat/uso terapêutico , Fator 2 Relacionado a NF-E2/genética , Tumores Neuroendócrinos/tratamento farmacológico , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Transdução de Sinais
12.
Spectrochim Acta A Mol Biomol Spectrosc ; 315: 124255, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38608562

RESUMO

The kidney allograft has been under continuous attack from diverse injuries since the very beginning of organ procurement, leading to a gradual decline in function, chronic fibrosis, and allograft loss. It is vital to routinely and precisely monitor the risk of injuries after renal transplantation, which is difficult to achieve because the traditional laboratory tests lack sensitivity and specificity, and graft biopsies are invasive with the risk of many complications and time-consuming. Herein, a novel method for the diagnosis of graft injury is demonstrated, using deep learning-assisted surface-enhanced Raman spectroscopy (SERS) of the urine analysis. Specifically, we developed a hybrid SERS substrate composed of gold and silver with high sensitivity to the urine composition under test, eliminating the need for labels, which makes measurements easy to perform and meanwhile results in extremely abundant and complex Raman vibrational bands. Deep learning algorithms were then developed to improve the interpretation of the SERS spectral fingerprints. The deep learning model was trained with SERS signals of urine samples of recipients with different injury types including delayed graft function (DGF), calcineurin-inhibitor toxicity (CNIT), T cell-mediated rejection (TCMR), antibody-mediated rejection (AMR), and BK virus nephropathy (BKVN), which explored the features of these types and achieved the injury differentiation with an overall accuracy of 93.03%. The results highlight the potential of combining label-free SERS spectroscopy with deep learning as a method for liquid biopsy of kidney allograft injuries, which can provide great potential to diagnose and evaluate allograft injuries, and thus extend the life of kidney allografts.


Assuntos
Aprendizado Profundo , Transplante de Rim , Análise Espectral Raman , Análise Espectral Raman/métodos , Humanos , Transplante de Rim/efeitos adversos , Aloenxertos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/urina , Ouro/química
13.
Front Endocrinol (Lausanne) ; 15: 1294638, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590820

RESUMO

As the incidence of type 2 diabetes mellitus (T2DM) is increasing rapidly and its consequences are severe, effective intervention and prevention, including sleep-related interventions, are urgently needed. As a component of sleep architecture, naps, alone or in combination with nocturnal sleep, may influence the onset and progression of T2DM. Overall, napping is associated with an increased risk of T2DM in women, especially in postmenopausal White women. Our study showed that napping >30 minutes (min) increased the risk of T2DM by 8-21%. In addition, non-optimal nighttime sleep increases T2DM risk, and this effect combines with the effect of napping. For nondiabetic patients, napping >30 min could increase the risks of high HbA1c levels and impaired fasting glucose (IFG), which would increase the risk of developing T2DM later on. For diabetic patients, prolonged napping may further impair glycemic control and increase the risk of developing diabetic complications (e.g., diabetic nephropathy) in the distant future. The following three mechanisms are suggested as interpretations for the association between napping and T2DM. First, napping >30 min increases the levels of important inflammatory factors, including interleukin 6 and C-reactive protein, elevating the risks of inflammation, associated adiposity and T2DM. Second, the interaction between postmenopausal hormonal changes and napping further increases insulin resistance. Third, prolonged napping may also affect melatonin secretion by interfering with nighttime sleep, leading to circadian rhythm disruption and further increasing the risk of T2DM. This review summarizes the existing evidence on the effect of napping on T2DM and provides detailed information for future T2DM intervention and prevention strategies that address napping.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Feminino , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/epidemiologia , Sono , Ritmo Circadiano , Inflamação
14.
Curr Issues Mol Biol ; 46(3): 2514-2527, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38534775

RESUMO

There has been debate about whether individuals with different color phenotypes should have different taxonomic status. In order to determine whether the different color phenotypes of Nedyopus patrioticus require separate taxonomic status or are simply synonyms, here, the complete mitochondrial genomes (mitogenomes) of two different colored N. patrioticus, i.e., red N. patrioticus and white N. patrioticus, are presented. The two mitogenomes were 15,781 bp and 15,798 bp in length, respectively. Each mitogenome contained 13 PCGs, 19 tRNAs, 2 rRNAs, and 1 CR, with a lack of trnI, trnL2, and trnV compared to other Polydesmida species. All genes were located on a single strand in two mitogenomes. Mitochondrial DNA analyses revealed that red N. patrioticus and white N. patrioticus did not show clear evolutionary differences. Furthermore, no significant divergence was discovered by means of base composition analysis. As a result, we suggest that white N. patrioticus might be regarded as a synonym for red N. patrioticus. The current findings confirmed the existence of color polymorphism in N. patrioticus, which provides exciting possibilities for future research. It is necessary to apply a combination of molecular and morphological methods in the taxonomy of millipedes.

15.
NPJ Precis Oncol ; 8(1): 77, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538696

RESUMO

Regulated cell death (RCD) plays a pivotal role in various biological processes, including development, tissue homeostasis, and immune response. However, a comprehensive assessment of RCD status and its associated features at the pan-cancer level remains unexplored. Furthermore, despite significant advancements in immune checkpoint inhibitors (ICI), only a fraction of cancer patients currently benefit from treatments. Given the emerging evidence linking RCD and ICI efficacy, we hypothesize that the RCD status could serve as a promising biomarker for predicting the ICI response and overall survival (OS) in patients with malignant tumors. We defined the RCD levels as the RCD score, allowing us to delineate the RCD landscape across 30 cancer types, 29 normal tissues in bulk, and 2,573,921 cells from 82 scRNA-Seq datasets. By leveraging large-scale datasets, we aimed to establish the positive association of RCD with immunity and identify the RCD signature. Utilizing 7 machine-learning algorithms and 18 ICI cohorts, we developed an RCD signature (RCD.Sig) for predicting ICI response. Additionally, we employed 101 combinations of 10 machine-learning algorithms to construct a novel RCD survival-related signature (RCD.Sur.Sig) for predicting OS. Furthermore, we obtained CRISPR data to identify potential therapeutic targets. Our study presents an integrative framework for assessing RCD status and reveals a strong connection between RCD status and ICI effectiveness. Moreover, we establish two clinically applicable signatures and identify promising potential therapeutic targets for patients with tumors.

16.
J Glob Health ; 14: 04069, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38515427

RESUMO

Background: China's fertility policy has dramatically changed in the past decade with the successive promulgation of the partial two-child policy, universal two-child policy and three-child policy. The trajectories of maternal and neonatal health accompanied the changes in fertility policy are unknown. Methods: We obtained data of 280 203 deliveries with six common pregnancy complications and thirteen perinatal outcomes between 2010 and 2021 in eastern China. The average annual percent change (AAPC) was calculated to evaluated the temporal trajectories of obstetric characteristics and adverse outcomes during this period. Then, the autoregressive integrated moving average (ARIMA) models were constructed to project future trend of obstetric characteristics and outcomes until 2027. Results: The proportion of advanced maternal age (AMA), assisted reproduction technology (ART) treatment, gestational diabetes mellitus (GDM), anaemia, thrombocytopenia, thyroid dysfunction, oligohydramnios, placental abruption, small for gestational age (SGA) infants, and congenital malformation significantly increased from 2010 to 2021. However, the placenta previa, large for gestational age (LGA) infants and stillbirth significantly decreased during the same period. The AMA and ART treatment were identified as independent risk factors for the uptrends of pregnancy complications and adverse perinatal outcomes. The overall caesarean section rate remained above 40%. Importantly, among multiparas, a previous caesarean section was found to be associated with a significantly reduced risk of hypertensive disorders of pregnancy (HDP), premature rupture of membranes (PROM), placenta previa, placental abruption, perinatal asphyxia, LGA infants, stillbirths, and preterm births. In addition, the ARIMA time series models predicted increasing trends in the ART treatment, GDM, anaemia, thrombocytopenia, postpartum haemorrhage, congenital malformation, and caesarean section until 2027. Conversely, a decreasing trend was predicted for HDP, PROM, and placental abruption premature, LGA infants, SGA infants, perinatal asphyxia, and stillbirth. Conclusions: Maternal and neonatal adverse outcomes became more prevalent from 2010 to 2021 in China. Maternal age and ART treatment were independent risk factors for adverse obstetric outcomes. The findings offered comprehensive trajectories for monitoring pregnancy complications and perinatal outcomes in China, and provided robust intervention targets in obstetric safety. The development of early prediction models and the implementation of prevention efforts for adverse obstetric events are necessary to enhance obstetric safety.


Assuntos
Descolamento Prematuro da Placenta , Anemia , Placenta Prévia , Complicações na Gravidez , Nascimento Prematuro , Trombocitopenia , Feminino , Humanos , Recém-Nascido , Gravidez , Asfixia , Cesárea , Estudos Transversais , Saúde do Lactente , Placenta , Placenta Prévia/epidemiologia , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos , Natimorto
17.
Protein Cell ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38366188

RESUMO

The progressive degradation in the trabecular meshwork (TM) is related to age-related ocular diseases like primary open-angle glaucoma. However, the molecular basis and biological significance of the aging process in TM have not been fully elucidated. Here, we established a dynamic single-cell transcriptomic landscape of aged macaque TM, wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM aging. Furthermore, we divided TM cells into 13 clusters and performed an in- depth analysis on cluster 0, which had the highest aging score and the most significant changes in cell proportions between the two groups. Ultimately, we found that the APOE gene was an important differentially expressed gene in cluster 0 during the aging process, highlighting the close relationship between cell migration and extracellular matrix regulation, and TM function. Our work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components, thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal range. Our work provides valuable insights for future clinical diagnosis and treatment of glaucoma.

18.
J Exp Clin Cancer Res ; 43(1): 47, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38342925

RESUMO

In tumor therapeutics, the transition from conventional cytotoxic drugs to targeted molecular therapies, such as those targeting receptor tyrosine kinases, has been pivotal. Despite this progress, the clinical outcomes have remained modest, with glioblastoma patients' median survival stagnating at less than 15 months. This underscores the urgent need for more specialized treatment strategies. Our review delves into the progression toward immunomodulation in glioma treatment. We dissect critical discoveries in immunotherapy, such as spotlighting the instrumental role of tumor-associated macrophages, which account for approximately half of the immune cells in the glioma microenvironment, and myeloid-derived suppressor cells. The complex interplay between tumor cells and the immune microenvironment has been explored, revealing novel therapeutic targets. The uniqueness of our review is its exhaustive approach, synthesizing current research to elucidate the intricate roles of various molecules and receptors within the glioma microenvironment. This comprehensive synthesis not only maps the current landscape but also provides a blueprint for refining immunotherapy for glioma, signifying a paradigm shift toward leveraging immune mechanisms for improved patient prognosis.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Células Supressoras Mieloides , Humanos , Glioma/patologia , Glioblastoma/patologia , Imunoterapia , Imunomodulação , Microambiente Tumoral , Neoplasias Encefálicas/tratamento farmacológico
19.
Genes (Basel) ; 15(2)2024 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-38397243

RESUMO

This study presents the complete mitochondrial genome (mitogenome) of Litostrophus scaber, which is the first mitogenome of the genus Litostrophus. The mitogenome is a circular molecule with a length of 15,081 bp. The proportion of adenine and thymine (A + T) was 69.25%. The gene ND4L used TGA as the initiation codon, while the other PCGs utilized ATN (A, T, G, C) as the initiation codons. More than half of the PCGs used T as an incomplete termination codon. The transcription direction of the L. scaber mitogenome matched Spirobolus bungii, in contrast to most millipedes. Novel rearrangements were found in the L. scaber mitogenome: trnQ -trnC and trnL1- trnP underwent short-distance translocations and the gene block rrnS-rrnL-ND1 moved to a position between ND4 and ND5, resulting in the formation of a novel gene order. The phylogenetic analysis showed that L. scaber is most closely related to S. bungii, followed by Narceus magnum. These findings enhance our understanding of the rearrangement and evolution of Diplopoda mitogenomes.


Assuntos
Artrópodes , Genoma Mitocondrial , Animais , Genoma Mitocondrial/genética , Filogenia , Composição de Bases , Artrópodes/genética , Códon de Iniciação
20.
ACS Omega ; 9(7): 7658-7667, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38405435

RESUMO

An efficient and noninvasive method of sensing lung cancer at an early stage is through detecting its biomarkers in the patient's exhaled breath. Acetone (C3H6O), benzene (C6H6), and isoprene (C5H8) emerged as crucial biomarkers, which were significantly elevated in lung cancer patients. Here, we investigated the adsorption behaviors of the three gas molecules on pristine and transition metal (TM)-doped (Au and Pd) SnS2 monolayers using the density functional theory (DFT) method. Our findings indicate that both Au- and Pd-doped SnS2 display higher adsorption energies (-0.53 to -1.313 eV) than that of the pure SnS2 monolayer (0.031 to 0.066 eV). Specifically, Pd-SnS2 exhibits smaller adsorption energy compared to that of Au-SnS2 when capturing C3H6O, C6H6, and C5H8. The estimated recovery times for Pd-SnS2 (8.016 × 10-4 to 16.02 s) are shorter compared to those of Au-SnS2 (1.11 to 1.14 × 1010 s), indicating the superior capability of Pd-SnS2 over Au-SnS2 as a reversible sensor. Afterward, calculations of band structure, projected density of states (PDOS), and charge transfer were performed, which further substantiates the more promising potentials for Pd-doped SnS2 monolayer as gas sensors over the others. Overall, our results suggest that Pd-SnS2 is a better candidate for C3H6O, C6H6, and C5H8 detection over Au-SnS2 and pristine SnS2.

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