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OBJECTIVE: To assess the visual quality, both subjective and objective, of cataract patients with varying axial lengths (AL) after PanOptix trifocal intraocular lens (IOL) implantation and investigated the lens tilt and its correlation with visual outcomes. METHODS: From July 2020 to June 2022, 70 patients (140 eyes) diagnosed with age-related cataracts and undergoing PanOptix implantation at Chongqing Eye and Vision Care Hospital, Aier Eye Hospital Group, were included. Patients were assigned to either the observation group (35 cases, 70 eyes with PanOptix trifocal IOL) or the control group (35 cases, 70 eyes with bifocal IOL). Patients were further subdivided based on AL into AL < 24 mm (observation group: 23 eyes; control group: 26 eyes) and AL ≥ 24 mm (observation group: 47 eyes; control group: 44 eyes). Postoperative follow-up lasted three months. Visual acuity (distant, intermediate, near), objective visual quality (Strehl ratio: SR, total eye modulation transfer function (MTF)), and visual aberrations were measured preoperatively and at 3 months post-operation. RESULTS: Postoperatively, all groups saw significant improvements in uncorrected distance visual acuity (UCDVA), uncorrected intermediate visual acuity (UCIVA), and uncorrected near visual acuity (UCNVA) compared to preoperative values (T0) (all P < 0.05). Notably, UCIVA was significantly better in the observation group than in the control group (P < 0.05). At three months (T1), reductions in total high-order aberration (tHOA), internal high-order aberration (iHOA), coma, and trefoil aberrations were observed in both groups compared to baseline, with more significant decreases in the observation group (all P < 0.05). Both SR and MTF cutoff showed marked improvement from T0 to T1, with the observation group experiencing greater enhancements (both P < 0.05). The defocus curve of the observation group showed a gentle slope between +0.5 D and -3.0 D, maintaining superior visual acuity compared to the control group (P < 0.05). Subjective visual quality scores at T1 were significantly higher than at T0 for both groups (P < 0.05), with patients in the observation group scoring higher than those in the control group across all AL categories (P < 0.05). Spearman correlation analysis indicated that the tilt after PanOptix trifocal IOL implantation was associated with tHOA (r = 0.273, P = 0.022), iHOA (r = 0.433, P < 0.001), Trefoil (r = 0.360, P = 0.002) and coma (r = 0.688, P < 0.001). CONCLUSION: PanOptix trifocal IOL implantation in cataract patients across different AL significantly enhances visual quality compared to bifocal IOLs, suggesting a strong case for its clinical adoption.
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Co-infection with porcine reproductive and respiratory syndrome virus (PRRSV) and Haemophilus parasuis (HPS) has severely restricted the healthy development of pig breeding. Exploring disease resistance of non-coding RNAs in pigs co-infected with PRRSV and HPS is therefore critical to complement and elucidate the molecular mechanisms of disease resistance in Kele piglets and to innovate the use of local pig germplasm resources in China. RNA-seq of lungs from Kele piglets with single-infection of PRRSV or HPS and co-infection of both pathogens was performed. Two hundred and twenty-five differentially expressed long non-coding RNAs (DElncRNAs) and 30 DEmicroRNAs (DEmiRNAs) were identified and characterized in the PRRSV and HPS co-infection (PRRSV-HPS) group. Compared with the single-infection groups, 146 unique DElncRNAs, 17 unique DEmiRNAs, and 206 target differentially expressed genes (DEGs) were identified in the PRRSV-HPS group. The expression patterns of 20 DEmiRNAs and DElncRNAs confirmed by real-time quantitative polymerase chain reaction (RT-qPCR) were consistent with those determined by high-throughput sequencing. In the PRRSV-HPS group, the target DEGs were enriched in eight immune Gene Ontology terms relating to two unique DEmiRNAs and 16 DElncRNAs, and the unique target DEGs participated the host immune response to pathogens infection by affecting 15 immune-related Kyoto Encyclopedia of Genes and Genomes enrichment pathways. Notably, competitive endogenous RNA (ceRNA) networks of different groups were constructed, and the ssc-miR-671-5p miRNA was validated as a potential regulatory factor to regulate DTX4 and AEBP1 genes to achieve innate antiviral effects and inhibit pulmonary fibrosis by dual-luciferase reporter assays. These results provided insight into further study on the molecular mechanisms of resistance to PRRSV and HPS co-infection in Kele piglets.
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This paper examines the influence of housing wealth on fertility outcomes through a regression discontinuity design based on a 2006 Chinese housing-market policy. Our analysis reveals that the positive impact of this policy on housing wealth significantly enhances the likelihood of fertility by 7.3 %. Our result implies that a 1 % increase in housing wealth can raise the fertility rate by 0.18 %. Furthermore, we observe that children born subsequent to the positive housing wealth shock exhibit improved health, not only at birth but also over the long term. Lastly, we present suggestive evidence suggesting that both parental pre-birth time allocation and parental health may help explain the documented positive effects of housing wealth on fertility rates.
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INTRODUCTION: Motor neurons differ from sensory neurons in aspects including origins and surrounding environment. Understanding the similarities and differences in molecular response to peripheral nerve injury (PNI) and regeneration between sensory and motor neurons is crucial for developing effective drug targets for CNS regeneration. However, genome-wide comparisons of molecular changes between sensory and motor neurons following PNI remains limited. OBJECTIVES: This study aims to investigate genome-wide convergence and divergence of injury response between sensory and motor neurons to identify novel drug targets for neural repair. METHODS: We analyzed two large-scale RNA-seq datasets of in situ captured sensory neurons (SNs) and motoneurons (MNs) upon PNI, retinal ganglion cells and spinal cord upon CNS injury. Additionally, we integrated these with other related single-cell level datasets. Bootstrap DESeq2 and WGCNA were used to detect and explore co-expression modules of differentially expressed genes (DEGs). RESULTS: We found that SNs and MNs exhibited similar injury states, but with a delayed response in MNs. We identified a conserved regeneration-associated module (cRAM) with 274 shared DEGs. Of which, 47% of DEGs could be changed in injured neurons supported by single-cell resolution datasets. We also identified some less-studied candidates in cRAM, including genes associated with transcription, ubiquitination (Rnf122), and neuron-immune cells cross-talk. Further in vitro experiments confirmed a novel role of Rnf122 in axon growth. Analysis of the top 10% of DEGs with a large divergence suggested that both extrinsic (e.g., immune microenvironment) and intrinsic factors (e.g., development) contributed to expression divergence between SNs and MNs following injury. CONCLUSIONS: This comprehensive analysis revealed convergent and divergent injury response genes in SNs and MNs, providing new insights into transcriptional reprogramming of sensory and motor neurons responding to axonal injury and subsequent regeneration. It also identified some novel regeneration-associated candidates that may facilitate the development of strategies for axon regeneration.
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Systemic lupus erythematosus (SLE) is a classic autoimmune disease characterized by abnormal autoantibodies, immune complex deposition, and tissue inflammation. Despite extensive research, the exact etiology and progression of SLE remain elusive. Cytidine/uridine monophosphate kinase 2 (CMPK2), a mitochondrial nucleoside monophosphate kinase, has garnered attention for its potential involvement in the development of various diseases, including SLE, where it has been observed to be dysregulated in affected individuals. However, the specific involvement of CMPK2 in the pathogenesis of SLE remains unclear. This study aims to clarify the expression level of CMPK2 in SLE CD4+ T cells and explore its impact on CD4+ T cells. The expression levels of the CMPK2 gene and the corresponding CMPK2 protein in CD4+ T cells of SLE patients were quantified using RT-qPCR and Western blot, respectively. Immunofluorescence and RT-qPCR were used to assess the mitochondrial function of SLE CD4+ T cells. Flow cytometry was used to assess CD4+ T cell activation and apoptosis levels. The impact of CMPK2 on CD4+ T cells was investigated by gene transfection experiment. We found that CMPK2 was significantly upregulated in SLE CD4+ T cells at both gene and protein levels. These cells demonstrated aberrant mitochondrial function, as evidenced by elevated mitochondrial reactive oxygen species (mtROS) levels, mitochondrial membrane potential, and mitochondrial DNA (mtDNA) copy number. Flow cytometry revealed a notable increase in both apoptosis and activation levels of CD4+ T cells in SLE patients. Gene transfection experiments showed that suppressing CMPK2 led to a significant improvement in these conditions. These findings suggest that CMPK2 may be involved in the pathogenesis of SLE by regulating mitochondrial dysfunction in CD4+ T cells and thus affecting CD4+ T cell activation and apoptosis. Our study may provide a new target for the treatment of SLE.
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Peripheral T cell lymphoma (PTCL) represents a group of heterogeneous hematological malignancies, which are notoriously challenging to treat and outcomes are typically poor. Over the past two decades, clinical prognostic indices for patient risk stratification have evolved, while several targeted agents are now available to complement combination chemotherapy in the frontline setting or as a salvage strategy. With further understanding of the molecular pathobiology of PTCL, several innovative approaches incorporating immunomodulatory agents, epigenetic therapies, oncogenic kinase inhibitors and immunotherapeutics have come to the forefront. In this review, we provide a comprehensive overview of the progress in developing clinical prognostic indices for PTCL and describe the broad therapeutic landscape, emphasizing novel targetable pathways that have entered early phase clinical studies.
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Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/terapia , Medição de Risco , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoterapia/métodos , Recidiva Local de Neoplasia , Terapia de Alvo Molecular/métodosRESUMO
BACKGROUND: The protein kinase domain containing cytoplasmic (PKDCC) gene (OMIM#618821) is associated with bone development. Biallelic variants in the PKDCC gene can cause rhizomelic limb shortening with dysmorphic features. CASE REPORT: A fetus was found to be rhizomelic limb shortening at 16 weeks of gestation and amniocentesis was performed at 19 weeks of gestation. Genomic DNA extracted from the amniotic fluid was subjected to chromosomal microarray analysis (CMA), and Trio-total whole-exome sequencing (Trio-WES). Sanger sequencing was used to verify the candidate pathogenic variants. CMA was normal, while Trio-WES identified two compound heterozygous variants in the PKDCC gene, namely c.417_c.423delCGGCGCG insTCATGGGCTCAGTACAC(p.G140fs*35) and c.345G>A (p.W115*,379). Then the fetus was aborted and the development of its bone cells were compared with that of a normal fetus of similar gestational age by histopathological examination. Clinical findings of the fetus were shortening humerus and femur, synophrys, much hair on the side face, simian line on the right palm, etc. Histopathological examination showed that the affected fetus had increased proliferative chondrocytes, widened proliferative bands, and delayed bone mineralization. CONCLUSIONS: We reported a prenatal case of rhizomelic shortening of limbs caused by compound heterozygous variants in the PKDCC gene, which emphasized the important role of Trio-WES for diagnosis of skeletal dysplasia in fetuses.
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Heterozigoto , Humanos , Feminino , Adulto , Gravidez , Mutação , Diagnóstico Pré-Natal , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas dos Membros/diagnóstico , Deformidades Congênitas dos Membros/patologiaRESUMO
Inherited ichthyosis comprises a series of heterogeneous dermal conditions; it mainly manifests as widespread hyperkeratosis, xerosis and scaling of the skin. At times, overlapping symptoms require differential diagnosis between ichthyosis and several other similar disorders. The present study reports seven patients with confirmed or suspected to be associated with ichthyosis by conducting a thorough clinical and genetic investigation. Genetic testing was conducted using wholeexome sequencing, with Sanger sequencing as the validation method. The MEGA7 program was used to analyze the conservation of amino acid residues affected by the detected missense variants. The enrolled patients exhibited ichthyosislike but distinct clinical manifestations. Genetic analysis identified diagnostic variations in the FLG, STS, KRT10 and SERPINB7 genes and clarified the carrying status of each variant in the respective family members. The two residues affected by the detected missense variants remained conserved across multiple species. Of note, the two variants, namely STS: c.452C>T(p.P151L) and c.647_650del(p.L216fs) are novel. In conclusion, a clear genetic differential diagnosis was made for the enrolled ichthyosisassociated patients; the study findings also extended the mutation spectrum of ichthyosis and provided solid evidence for the counseling of the affected families.
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Sequenciamento do Exoma , Proteínas Filagrinas , Ictiose , Ceratodermia Palmar e Plantar , Linhagem , Esteril-Sulfatase , Humanos , Feminino , Masculino , Ceratodermia Palmar e Plantar/genética , Ceratodermia Palmar e Plantar/diagnóstico , Ceratodermia Palmar e Plantar/patologia , Criança , Ictiose/genética , Ictiose/diagnóstico , Adulto , Testes Genéticos , Serpinas/genética , Queratina-10/genética , Adolescente , Pré-Escolar , Mutação de Sentido Incorreto , Mutação , Adulto Jovem , Predisposição Genética para DoençaRESUMO
Background: The c-met proto-oncogene (MET) serves as a significant primary oncogenic driver in non-small cell lung cancer (NSCLC) and has the potential to fuse with other genes, such as KIF5B, although it occurs infrequently. Only a limited number of reported cases have examined the clinical efficacy of crizotinib in patients with KIF5B-MET gene fusion, with no known data regarding acquired resistance to crizotinib and its potential mechanisms. In this report, we present the clinical progression of a female patient diagnosed with NSCLC and harboring a KIF5B-MET gene fusion. Case description: The patient initially exhibited partial response to first-line crizotinib treatment, albeit for a short duration and with limited efficacy. Subsequent disease progression revealed the emergence of a secondary MET mutation, specifically MET Y1230H, leading to acquired resistance to crizotinib. Conclusion: The reporting of this case is imperative for informing clinical practice, given the uncommon occurrence of NSCLC with MET fusion, displaying responsiveness to MET tyrosine kinase inhibitor therapy, as well as the emergence of the secondary Y1230H alteration as a potential resistance mechanism.
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A phytochemical study of the ethanol extract from Ailanthus altissima (Mill.) Swingle leaves resulted in the isolation of four new monoterpenoids (1-3, 5). The structures were elucidated using HRESIMS data, NMR spectroscopic data, quantum chemical calculations for NMR and ECD, and custom DP4+ probability analysis. Additionally, the absolute configuration of sugar was determined by acid hydrolysis. Compounds 1-4 are cyclogeraniane monocyclic monoterpenes, while compound 5 contains an acyclic mycrane monoterpenes skeleton. Anti-tyrosinase, anti-acetylcholinesterase, and anti-butyrylcholinesterase activities were tested. Compound 1 showed notable anti-acetylcholinesterase activity, and compound 3 exhibited significant inhibitory effects on anti-tyrosinase activity. Furthermore, the potential binding sites of compounds 1 and 3 were predicted by molecular docking.
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Ailanthus , Simulação de Acoplamento Molecular , Monoterpenos , Compostos Fitoquímicos , Folhas de Planta , Ailanthus/química , Estrutura Molecular , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Monofenol Mono-Oxigenase/antagonistas & inibidores , Acetilcolinesterase/metabolismo , Butirilcolinesterase/metabolismoRESUMO
OBJECTIVE: γδ T cells are a distinct subset of unconventional T cells, which link innate and adaptive immunity by secreting cytokines and interacting with other immune cells, thereby modulating immune responses. As the first line of host defense, γδ T cells are essential for mucosal homeostasis and immune surveillance. When abnormally activated or impaired, γδ T cells can contribute to pathogenic processes. Accumulating evidence has revealed substantial impacts of γδ T cells on the pathogenesis of cancers, infections, and immune-inflammatory diseases. γδ T cells exhibit dual roles in cancers, promoting or inhibiting tumor growth, depending on their phenotypes and the clinical stage of cancers. During infections, γδ T cells exert high cytotoxic activity in infectious diseases, which is essential for combating bacterial and viral infections by recognizing foreign antigens and activating other immune cells. γδ T cells are also implicated in the onset and progression of immune-inflammatory diseases. However, the specific involvement and underlying mechanisms of γδ T cells in oral diseases have not been systematically discussed. METHODS: We conducted a systematic literature review using the PubMed/MEDLINE databases to identify and analyze relevant literature on the roles of γδ T cells in oral diseases. RESULTS: The literature review revealed that γδ T cells play a pivotal role in maintaining oral mucosal homeostasis and are involved in the pathogenesis of oral cancers, periodontal diseases, graft-versus-host disease (GVHD), oral lichen planus (OLP), and oral candidiasis. γδ T cells mainly influence various pathophysiological processes, such as anti-tumor activity, eradication of infection, and immune response regulation. CONCLUSION: This review focuses on the involvement of γδ T cells in oral diseases, with a particular emphasis on the main functions and underlying mechanisms by which γδ T cells influence the pathogenesis and progression of these conditions. This review underscores the potential of γδ T cells as therapeutic targets in managing oral health issues.
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Doenças da Boca , Humanos , Doenças da Boca/imunologia , Animais , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linfócitos Intraepiteliais/imunologia , Doença Enxerto-Hospedeiro/imunologia , Linfócitos T/imunologiaRESUMO
OBJECTIVE: Sotos syndrome (SOTOS) is an uncommon genetic condition that manifests itself with the following distinctive features: prenatal overgrowth, facial abnormalities, and intellectual disability. This disorder is often associated with haploinsufficiency of the nuclear receptor-binding SET domain protein 1 (NSD1)gene. We investigated four pediatric cases characterized by early-onset overgrowth and developmental delay. The primary objective of this study was to achieve accurate genetic diagnoses. DESIGN&METHODS: A sequential analysis approach comprising chromosomal karyotyping, whole exome sequencing, and microarray analysis was conducted. RESULTS: All four cases exhibited variations in the NSD1 gene, with the identification of four previously unreported de novo variants, each specific to one case.Specifically, Case 1 carried the NSD1 (NM_022455): c.2686 C > T(p.Q896X) variant, Case 2 had the NSD1 (NM_022455): c.2858_2859delCT(p.S953X) variant, Case 3 displayed a chromosomal aberration, chr5: 5q35.2q35.3(176,516,604-176,639,249)×1, which encompassed the 5'-untranslated region of NSD1, and Case 4 harbored the NSD1 (NM_022455): c.6397T > G(p.C2133G) variant. CONCLUSION: This study not only provided precise diagnoses for these cases but also supplied significant evidence to facilitate informed consultations. Furthermore, our findings expanded the spectrum of mutations associated with SOTOS.
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Histona-Lisina N-Metiltransferase , Síndrome de Sotos , Humanos , Histona-Lisina N-Metiltransferase/genética , Síndrome de Sotos/genética , Masculino , Feminino , Pré-Escolar , Criança , Lactente , Peptídeos e Proteínas de Sinalização Intracelular/genética , Sequenciamento do Exoma , Mutação , Cariotipagem , Histona Metiltransferases/genética , Proteínas Nucleares/genéticaRESUMO
Phosphatase and tensin homologue deleted on chromosome ten (PTEN) was initially recognized as a significant regulator of cancer suppression and could impede cancer cell survival, proliferation, and energy metabolism. PTEN is highly expressed in neurons and performs crucial functions in neurogenesis, synaptogenesis, and neuronal survival. Disruption of PTEN activity may also result in abnormal neuronal function and is associated with various neurological disorders, including stroke, seizures, and autism. Although several studies have shown that PTEN is involved in the development and degenerative processes of the nervous system, there is still a lack of in-depth studies that summarize and analyse patterns of cooperation between authors, institutions, countries, and journals, as well as research hotspots and trends in this important field. To identify and further visualize the cooperation and comprehend the development and trends of PTEN in the nervous system, especially in neural development and neurological diseases, we used a bibliometric analysis to identify relevant publications on this topic. We first found that the number of publications displayed a growing trend with time, but this was not stable. Universities, institutions, and authors from the United States are leading in this area of research. In addition, many cutting-edge research results have been discovered, such as key regulatory molecules and cellular mechanisms of PTEN in the nervous system, which may provide novel intervention targets and precise therapeutic strategies for related pathological injuries and diseases. Finally, the literature published within the last 5 years is discussed to identify future research trends regarding PTEN in the nervous system. Taken together, our findings, analysed using bibliometrics, may reflect research hotspots and trends, providing a reference for studying PTEN in the nervous system, especially in neural development and neurological diseases. These findings can assist new researchers in developing their research interests and gaining basic information. Moreover, our findings also may provide precise clinical guidelines and strategies for treating nervous system injuries and diseases caused by PTEN dysfunction.
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With the development of single-cell sequencing technology, the cellular composition of more and more tissues is being elucidated. As the whole nervous system has been extensively studied, the cellular composition of the peripheral nerve has gradually been revealed. By summarizing the current sequencing data, we compile the heterogeneities of cells that have been reported in the peripheral nerves, mainly the sciatic nerve. The cellular variability of Schwann cells, fibroblasts, immune cells, and endothelial cells during development and disease has been discussed in this review. The discovery of the architecture of peripheral nerves after injury benefits the understanding of cellular complexity in the nervous system, as well as the construction of tissue engineering nerves for nerve repair and axon regeneration.
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Axônios , Traumatismos dos Nervos Periféricos , Humanos , Axônios/fisiologia , Células Endoteliais , Regeneração Nervosa/fisiologia , Células de Schwann/fisiologia , Nervo Isquiático/lesões , Traumatismos dos Nervos Periféricos/genéticaRESUMO
RNAs play crucial roles in various essential biological functions, including catalysis and gene regulation. Despite the widespread use of coarse-grained (CG) models/simulations to study RNA 3D structures and dynamics, their direct application is challenging due to the lack of atomic detail. Therefore, the reconstruction of full atomic structures is desirable. In this study, we introduced a straightforward method called ABC2A for reconstructing all-atom structures from RNA CG models. ABC2A utilizes diverse nucleotide fragments from known structures to assemble full atomic structures based on the CG atoms. The diversification of assembly fragments beyond standard A-form ones, commonly used in other programs, combined with a highly simplified structure refinement process, ensures that ABC2A achieves both high accuracy and rapid speed. Tests on a recent large dataset of 361 RNA experimental structures (30-692 nt) indicate that ABC2A can reconstruct full atomic structures from three-bead CG models with a mean RMSD of ~0.34 Å from experimental structures and an average runtime of ~0.5 s (maximum runtime < 2.5 s). Compared to the state-of-the-art Arena, ABC2A achieves a ~25% improvement in accuracy and is five times faster in speed.
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Simulação de Dinâmica Molecular , RNA , RNA/química , NucleotídeosRESUMO
Copper is an essential trace element, and plays a vital role in numerous physiological processes within the human body. During normal metabolism, the human body maintains copper homeostasis. Copper deficiency or excess can adversely affect cellular function. Therefore, copper homeostasis is stringently regulated. Recent studies suggest that copper can trigger a specific form of cell death, namely, cuproptosis, which is triggered by excessive levels of intracellular copper. Cuproptosis induces the aggregation of mitochondrial lipoylated proteins, and the loss of iron-sulfur cluster proteins. In neurodegenerative diseases, the pathogenesis and progression of neurological disorders are linked to copper homeostasis. This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases. This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.
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Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Cobre , Morte Celular , Proteínas MitocondriaisRESUMO
The use of central nervous system (CNS) prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) remains controversial. Although uncommon, CNS relapses are invariably fatal in this otherwise curable disease. Accurate identification of patients at risk and the optimal approach to CNS prophylaxis therefore remains an area of unmet need. The existing literature, largely retrospective in nature, provides mixed conclusions regarding the efficacy of CNS prophylaxis. The utility of CNS prophylaxis has itself been challenged. In this review, we dissect the issues which render the value of CNS prophylaxis uncertain. We first compare international clinical guidelines for CNS prophylaxis. We then interrogate the factors that should be used to identify high-risk patients accurately. We also explore how clinical patterns of CNS relapse have changed in the pre-rituximab and rituximab era. We then discuss the efficacy of CNS-directed approaches, intensification of systemic treatment and other novel approaches in CNS prophylaxis. Improved diagnostics for early detection of CNS relapses and newer therapeutics for CNS prophylaxis are areas of active investigation. In an area where prospective, randomized studies are impracticable and lacking, guidance for the use of CNS prophylaxis will depend on rigorous statistical review of retrospective data.
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Carolacton, a naturally occurring MTHFD1 inhibitor, exhibits potent inhibitory activity against various RNA viruses including SARS-CoV-2. Herein, we present a concise total synthesis of carolacton, featuring the Krische allylation, Marshall coupling, NHK coupling, and RCM reaction as key elements. Additionally, we have synthesized three simplified carolacton analogues, one of which, namely, 14-demethyl-carolacton, exhibited notable antiviral activity. The present work paves the way for further exploration of the therapeutic potential of carolacton and its analogues.
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Antivirais , Macrolídeos , Macrolídeos/farmacologia , Antivirais/farmacologiaRESUMO
This study was designed to compare the beneficial effects of paricalcitol combined with or without cinacalcet on calcium and phosphorus metabolism in patients undergoing maintenance hemodialysis (MHD). A total of 140 patients who received MHD in our hospital from March 2021 to March 2022 were randomly divided into a control group (intravenous paricalcitol, n = 70) and a test group (intravenous paricalcitol combined with oral cinacalcet, n = 70). Clinical baseline data and relevant laboratory parameters before treatment were compared. Additionally, calcium, phosphorus, intact parathyroid hormone in serum were measured and compared between the 2 groups before treatment and 1, 2, 3, 4, 5, 6, 9, 10, and 12 months after treatment. As a result, comparison before treatment demonstrated no significant difference in baseline data such as age, sex, and most laboratory parameters between the 2 groups (P > .05), but there was a significant difference in mean corpuscular volume (P < .001). The serum phosphorus level decreased and calcium level increased significantly in the 2 groups after treatment, while the intact parathyroid hormone level showed no significant change within 12 months of treatment (P > .05). In addition, the combined treatment for 6-12 months caused a much lower phosphorus level (P < .05) and higher calcium level (P < .05) than the treatment with paricalcitol alone, and the difference increased with the extension of treatment time. Collectively, paricalcitol combined with cinacalcet, which is more effective than paricalcitol alone, has a positive effect on calcium and phosphorus metabolism in patients receiving MHD.
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Cálcio , Hiperparatireoidismo Secundário , Humanos , Cinacalcete/uso terapêutico , Cálcio/uso terapêutico , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/etiologia , Diálise Renal , Hormônio Paratireóideo/uso terapêutico , FósforoRESUMO
Bleeding to death accounts for around 30-40% of all trauma-related fatalities. Current hemostatic materials are mainly mono-functional or have insufficient hemostatic capacity. Nanoclay has been recently shown to accelerate hemostasis, improve wound healing, and provide the resulting multifunctional hemostatic materials antibacterial, anti-inflammatory, and healing-promoting due to its distinctive morphological structure and physicochemical properties. Herein, the chemical design and action mechanism of nanoclay-based hemostatic, antibacterial, and pro-wound healing materials in the context of wound healing are discussed. The physiological processes of hemostasis and wound healing to elucidate the significance of nanoclay for functional wound hemostatic dressing design are outlined. A summary of the features of various nanoclay and product types used in wound hemostatic dressings is provided. Nanoclay can be antimicrobial due to the slow release of metal ions and has an abundant surface charge allowing for high affinity for proteins and cells, which can activate the coagulation reaction or facilitate tissue repair. Nanoclay with a microporous structure can be used as drug carriers to create composites critical for inhibiting bacterial growth on wounds or promoting the regeneration of vascular, muscle, and skin tissues. Directions for further research and innovation of nanoclay-based multifunctional materials for hemostasis and tissue regeneration are explored.