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1.
Sci Adv ; 10(21): eadk8908, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38781342

RESUMO

DNA replication is a vulnerable cellular process, and its deregulation leads to genomic instability. Here, we demonstrate that chromobox protein homolog 3 (CBX3) binds replication protein A 32-kDa subunit (RPA2) and regulates RPA2 retention at stalled replication forks. CBX3 is recruited to stalled replication forks by RPA2 and inhibits ring finger and WD repeat domain 3 (RFWD3)-facilitated replication restart. Phosphorylation of CBX3 at serine-95 by casein kinase 2 (CK2) kinase augments cadherin 1 (CDH1)-mediated CBX3 degradation and RPA2 dynamics at stalled replication forks, which permits replication fork restart. Increased expression of CBX3 due to gene amplification or CK2 inhibitor treatment sensitizes prostate cancer cells to poly(ADP-ribose) polymerase (PARP) inhibitors while inducing replication stress and DNA damage. Our work reveals CBX3 as a key regulator of RPA2 function and DNA replication, suggesting that CBX3 could serve as an indicator for targeted therapy of cancer using PARP inhibitors.


Assuntos
Caseína Quinase II , Replicação do DNA , Inibidores de Poli(ADP-Ribose) Polimerases , Proteína de Replicação A , Humanos , Caseína Quinase II/metabolismo , Caseína Quinase II/genética , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Proteína de Replicação A/metabolismo , Proteína de Replicação A/genética , Linhagem Celular Tumoral , Proteólise , Dano ao DNA , Fosforilação , Proteínas Cromossômicas não Histona
2.
Cell Rep ; 43(5): 114193, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38709635

RESUMO

Astrocytes play vital roles in blood-brain barrier (BBB) maintenance, yet how they support BBB integrity under normal or pathological conditions remains poorly defined. Recent evidence suggests that ion homeostasis is a cellular mechanism important for BBB integrity. In the current study, we investigated the function of an astrocyte-specific pH regulator, Slc4a4, in BBB maintenance and repair. We show that astrocytic Slc4a4 is required for normal astrocyte morphological complexity and BBB function. Multi-omics analyses identified increased astrocytic secretion of CCL2 coupled with dysregulated arginine-NO metabolism after Slc4a4 deletion. Using a model of ischemic stroke, we found that loss of Slc4a4 exacerbates BBB disruption, which was rescued by pharmacological or genetic inhibition of the CCL2-CCR2 pathway in vivo. Together, our study identifies the astrocytic Slc4a4-CCL2 and endothelial CCR2 axis as a mechanism controlling BBB integrity and repair, while providing insights for a therapeutic approach against BBB-related CNS disorders.

3.
Front Pharmacol ; 15: 1374183, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756380

RESUMO

The human voltage-gated sodium channel Nav1.7 is a widely proven target for analgesic drug studies. ProTx2, a 30-residue polypeptide from Peruvian green tarantula venom, shows high specificity to activity against human Nav1.7, suggesting its potential to become a non-addictive analgesic. However, its high sensitivity to human Nav1.4 raises concerns about muscle side effects. Here, we engineered three mutants (R13A, R13D, and K27Y) of ProTx2 to evaluate their pharmacological activities toward Nav1.7 and Nav1.4. It is demonstrated that the mutant R13D maintained the analgesic effect in mice while dramatically reducing its muscle toxicity compared with ProTx2. The main reason is the formation of a strong electrostatic interaction between R13D and the negatively charged amino acid residues in DII/S3-S4 of Nav1.7, which is absent in Nav1.4. This study advances our understanding and insights on peptide toxins, paving the way for safer, effective non-addictive analgesic development.

4.
Funct Plant Biol ; 512024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38801747

RESUMO

Rapid wound healing is crucial in protecting sweet potatoes (Ipomoea batatas ) against infection, water loss and quality deterioration during storage. The current study investigated how acibenzolar-S-methyl (ASM) treatment influenced wound healing in harvested sweet potatoes by investigating the underlying mechanism. It was found that ASM treatment of wounded sweet potatoes induced a significant accumulation of lignin at the wound sites, which effectively suppressed weight loss. After 4days of healing, the lignin content of ASM-treated sweet potatoes was 41.8% higher than that of untreated ones, and the weight loss rate was 20.4% lower. Moreover, ASM treatment increased the ability of sweet potatoes to defend against wounding stress through enhancing processes such as increased production of reactive oxygen species (ROS), activation of enzymes involved in the ROS metabolism (peroxidase, superoxide dismutase and catalase) and phenylpropanoid pathway (phenylalanine ammonia lyase, cinnamate-4-hydroxylase, 4-coumarate-CoA ligase and cinnamyl alcohol dehydrogenase), and intensive synthesis of phenolics and flavonoids. These results suggest that treating harvested sweet potatoes with ASM promotes wound healing through the activation of the ROS metabolism and phenylpropanoid pathway.


Assuntos
Ipomoea batatas , Lignina , Espécies Reativas de Oxigênio , Ipomoea batatas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Lignina/metabolismo , Cicatrização/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Fenóis/metabolismo , Fenilalanina Amônia-Liase/metabolismo
5.
Phys Rev Lett ; 132(8): 086101, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38457702

RESUMO

The exploration of solid-solid phase transition suffers from the uncertainty of how atoms in two crystal structures match. We devised a theoretical framework to describe and classify crystal-structure matches (CSM). Such description fully exploits the translational and rotational symmetries and is independent of the choice of supercells. This is enabled by the use of the Hermite normal form, an analog of reduced echelon form for integer matrices. With its help, exhausting all CSMs is made possible, which goes beyond the conventional optimization schemes. In an example study of the martensitic transformation of steel, our enumeration algorithm finds many candidate CSMs with lower strains than known mechanisms. Two long-sought CSMs accounting for the most commonly observed Kurdjumov-Sachs orientation relationship and the Nishiyama-Wassermann orientation relationship are unveiled. Given the comprehensiveness and efficiency, our enumeration scheme provide a promising strategy for solid-solid phase transition mechanism research.

6.
Phys Rev E ; 109(2-1): 024118, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38491632

RESUMO

The supercritical region is often described as uniform with no definite transitions. The distinct behaviors of the matter therein, e.g., as liquidlike and gaslike, however, suggest "supercritical boundaries." Here we provide a mathematical description of these phenomena by revisiting the Yang-Lee theory and introducing a complex phase diagram, specifically a four-dimensional (4D) one with complex T and p. While the traditional 2D phase diagram with real temperature T and pressure p values (the physical plane) lacks Lee-Yang (LY) zeros beyond the critical point, preventing the occurrence of criticality, the off-plane zeros in this 4D scenario still induce critical anomalies in various physical properties. This relationship is evidenced by the correlation between the Widom line and LY edges in van der Waals, 2D Ising model, and water. The diverged supercritical boundaries manifest the high-dimensional feature of the phase diagram: e.g., when LY zeros of complex T or p are projected onto the physical plane, boundaries defined by isobaric heat capacity C_{p} or isothermal compression coefficient K_{T} emanates. These results demonstrate the incipient phase transition nature of the supercritical matter.

7.
Mater Horiz ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38497840

RESUMO

Poly(amidoxime) (PAO) has been recognized as the most potential candidate for extracting uranium from seawater, owing to its merits of outstanding uranium affinity, low cost, and large-scale production. Despite remarkable achievements, existing PAO sorbents suffer from unsatisfactory uranium extraction efficiency and selectivity, as imposed by the inherently sluggish uranium adsorption kinetics and inevitable spatial configuration transition of amidoxime, which diminishes uranium affinity. Herein, we discover a facile and integrated design to elaborate a PAO/MXene nanocomposite that delivers ultrahigh and durable uranium/vanadium (U/V) selectivity. The key to our design lies in harnessing MXene-enabled strong intermolecular interactions to PAO to minimize the spatial configuration transition of amidoxime and stabilizing its superior uranium affinity, as well as creating a separated photothermal interface to maximize temperature-strengthened affinity for uranium over vanadium. Such a synergetic effect allows the nanocomposite to acquire over a 4-fold improvement in U/V selectivity compared to that of pure PAO as well as an unprecedented distribution coefficient of uranium compared to most state-of-the-art sorbents. We further demonstrate that our nanocomposite exhibits durable U/V selectivity with negligible attenuation and good antibacterial ability even in long-term operation. The design concept and extraordinary performance in this study bring PAO-based sorbents a step closer to practical uranium extraction from seawater.

8.
Bioengineering (Basel) ; 11(3)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38534499

RESUMO

The construction of medical knowledge graphs (MKGs) is steadily progressing from manual to automatic methods, which inevitably introduce noise, which could impair the performance of downstream healthcare applications. Existing error detection approaches depend on the topological structure and external labels of entities in MKGs to improve their quality. Nevertheless, due to the cost of manual annotation and imperfect automatic algorithms, precise entity labels in MKGs cannot be readily obtained. To address these issues, we propose an approach named Enhancing error detection on Medical knowledge graphs via intrinsic labEL (EMKGEL). Considering the absence of hyper-view KG, we establish a hyper-view KG and a triplet-level KG for implicit label information and neighborhood information, respectively. Inspired by the success of graph attention networks (GATs), we introduce the hyper-view GAT to incorporate label messages and neighborhood information into representation learning. We leverage a confidence score that combines local and global trustworthiness to estimate the triplets. To validate the effectiveness of our approach, we conducted experiments on three publicly available MKGs, namely PharmKG-8k, DiseaseKG, and DiaKG. Compared with the baseline models, the Precision@K value improved by 0.7%, 6.1%, and 3.6%, respectively, on these datasets. Furthermore, our method empirically showed that it significantly outperformed the baseline on a general knowledge graph, Nell-995.

9.
Nat Commun ; 15(1): 1871, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424044

RESUMO

CDK4/6 inhibitors (CDK4/6i) show anticancer activity in certain human malignancies, such as breast cancer. However, their application to other tumor types and intrinsic resistance mechanisms are still unclear. Here, we demonstrate that MYC amplification confers resistance to CDK4/6i in bladder, prostate and breast cancer cells. Mechanistically, MYC binds to the promoter of the E3 ubiquitin ligase KLHL42 and enhances its transcription, leading to RB1 deficiency by inducing both phosphorylated and total pRB1 ubiquitination and degradation. We identify a compound that degrades MYC, A80.2HCl, which induces MYC degradation at nanomolar concentrations, restores pRB1 protein levels and re-establish sensitivity of MYC high-expressing cancer cells to CDK4/6i. The combination of CDK4/6i and A80.2HCl result in marked regression in tumor growth in vivo. Altogether, these results reveal the molecular mechanisms underlying MYC-induced resistance to CDK4/6i and suggest the utilization of the MYC degrading molecule A80.2HCl to potentiate the therapeutic efficacy of CDK4/6i.


Assuntos
Neoplasias da Mama , Proteínas Inibidoras de Quinase Dependente de Ciclina , Humanos , Masculino , Pelve , Regiões Promotoras Genéticas , Próstata , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Quinase 4 Dependente de Ciclina/genética , Quinase 6 Dependente de Ciclina/genética , Inibidores de Proteínas Quinases
10.
Heliyon ; 10(4): e26034, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38370265

RESUMO

From the perspective of ecosystem attributes, this research was conducted to explore the impact of people's adaptation and response to their perception of environmental risks on their preference for sustainable development strategies and the realization of a circular economy based on Social Judgment Theory and the Value-Belief-Norm (VBN) theory. To achieve the goal, three substudies were conducted using questionnaire surveys-the first substudy aimed to examine the influence of ecological attributes on environmental risk perception (ERP). The second substudy attempted to understand the intricate connection between ERP and justice, while the third study explored the relationship between justice and SDS (sustainable development strategies) and CEG (realization of a circular economy). The results indicate the following: (1) The first substudy reveals that ecological attributes impact environmental risk perception (ERP), with different environmental values exerting distinct influences. (2) The second substudy suggests that ERP facilitates the realization of social, environmental, and ecological justice, but people's preference for a specific economic growth strategy will affect their tendency to realize justice. (3) The third substudy shows that sustainability strategies (i.e., sustainable production, consumption, and use) mediate the relationship between justice and circular economy goals (CEG). Among the three strategies, sustainable use plays the most significant mediating role. The research outcomes underscore the importance of prioritizing sustainable use in future research in theory and practice.

11.
Ecotoxicol Environ Saf ; 271: 115963, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38232526

RESUMO

As a fungicide with the characteristics of high effectiveness, internal absorption and broad spectrum, imazalil is widely used to prevent and treat in fruits and vegetables. Here, pregnant C57BL/6 mice were exposed to imazalil at dietary levels of 0, 0.025‰, and 0.25‰ through drinking water during pregnancy and lactation. We then analyzed the phenotype, metabolome, and expression of related genes and proteins in the livers of mice. There was a marked decrease in the body and liver weights of male offspring mice after maternal imazalil exposure, while this effect on the dam and female offspring was slight. Metabolomics analyses revealed that imazalil significantly altered the metabolite composition of liver samples from both dams and offspring. The preliminary results of the analysis indicated that glucolipid metabolism was the pathway most significantly affected by imazalil. We performed a coabundance association analysis of metabolites with significant changes in the pathway of glycolipid metabolism, and IMZ altered the networks of both dams and offspring compared with the network in control mice, especially in male offspring. The hepatic triglyceride, non-esterified fatty acid and glucose levels were increased significantly in the dams but decreased significantly in male offspring after maternal imazalil exposure. Furthermore, the expression levels of genes associated with glycolipid metabolism and m6A RNA methylation were significantly affected by maternal intake of imazalil. Imazalil-induced glucolipid metabolism disturbance was highly correlated with m6A RNA methylation. In conclusion, maternal imazalil exposure resulted in glucolipid metabolism disturbance and abnormal m6A RNA methylation in the livers of dams and offspring mice. We expected that the information acquired in this study will provide novel evidence for understanding the effect of maternal imazalil exposure on potential health risks.


Assuntos
Imidazóis , Fígado , Metilação de RNA , Gravidez , Camundongos , Masculino , Feminino , Animais , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Glicolipídeos/metabolismo
12.
Drug Alcohol Depend ; 256: 111094, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38262198

RESUMO

BACKGROUND: Methamphetamine (MA) use increases the risk of age-related diseases. However, it remains uncertain whether MA use exhibits accelerated biological aging, as indicated by telomere length (TL), a proposed marker of aging. Here we conducted studies in both humans and rats to investigate the association between MA use and TL. METHODS: We recruited 125 male MA users and 66 healthy controls, aged 30-40 years. MA users were diagnosed using DSM-5 criteria and categorized into two groups: non-severe (n = 78) and severe (n = 47) MA use disorder (MUD). MA-treated conditioned place preference (CPP) rats were utilized to validate our clinical investigations. TL was assessed using real-time polymerase chain reaction. RESULTS: At clinical levels, MA users exhibited significantly shorter leukocyte TL compared to healthy controls. Among MA users, individuals with severe MUD had significantly shorter leukocyte TL than those with non-severe MUD. Importantly, both univariate and multivariate linear regression analyses demonstrated a negative association between the severity of MA use and leukocyte TL. In a rat model of MA-induced CPP, leukocyte TL was also significantly shortened after MA administration, especially in rats with higher CPP expression or reinstatement scores. CONCLUSION: MA use shortened TL, and the severity of MA use was negatively correlated with TL. These findings provide new insights into the pathophysiology of accelerated aging caused by MA use and may have implications for identifying biomarkers and developing novel treatment strategies for MUD.


Assuntos
Envelhecimento , Metanfetamina , Humanos , Adulto , Animais , Ratos , Masculino , Manual Diagnóstico e Estatístico de Transtornos Mentais , Leucócitos , Metanfetamina/farmacologia , Telômero
13.
Sci Total Environ ; 912: 169154, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38065501

RESUMO

Submerged plants constitute a vital component of shallow lake ecosystems, where water depth and sediment nitrogen­phosphorus content are two key factors influencing their growth. This study focuses on Vallisneria natans and investigates the morphological and physiological changes of V. natans under the interaction of three water depth gradients and two different sediment nutrient levels. It explores the mechanisms through which varying sediment nutrient conditions under different water depths affect the growth of V. natans. The results indicate that both independent and interactive effects of water depth and sediment nutrient status significantly impact the morphology, antioxidant enzyme activity, and photosynthetic pigment content of V. natans, with water depth having a greater influence. To adapt to increased water depth-induced light stress, V. natans responds morphologically by increasing leaf length, leaf width, and decreasing maximum root length. Physiologically, it enhances its antioxidant regulation capacity and photosynthetic efficiency by increasing antioxidant enzyme activity, root vitality, and photosynthetic pigment content to counter weak light stress. However, these adaptations are insufficient to cope with excessively deep waters (200 cm). Sediment nutrient levels primarily control the growth of V. natans by affecting its root system. When sediment nitrogen and phosphorus content is lower, V. natans exhibits greater total root volume and surface area to enhance nutrient absorption efficiency. Water depth not only directly influences the growth of submerged plants but may also impact the migration and transformation of phosphorus in sediments, further exacerbating its effects on the growth of these plants, thus accelerating the regime shift of shallow lakes. Therefore, this study reveals V. natans' response strategies to varying water depths and sediment nutrient levels, determining suitable water levels and sediment nutrient conditions for its growth. These research findings provide a scientific basis for water level management and ecological restoration of submerged aquatic plants in shallow lakes.


Assuntos
Ecossistema , Hydrocharitaceae , Água , Antioxidantes , Hydrocharitaceae/fisiologia , Lagos , Nitrogênio , Fósforo , Nutrientes
14.
PhytoKeys ; 234: 203-218, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37927971

RESUMO

A new species of Anoectochilus (Orchidaceae) from Guangxi, China, A.zhongshanensis, is described here, which was identified based on phylogenetic studies adopting combined plastid markers (rbcL-matK-trnL-F), morphological observation and chemical analysis. Molecular phylogenetic results support the systematic status of A.zhongshanensis as a new species in Anoectochilus genus. Morphologically, this new species is similar to A.zhejiangensis and A.malipoensis, but differs by its characteristic labellum and column, including the hastate or scalpel-shaped lobes of epichile, forward curved and pinnately divided cristate lobes at both sides of the mesochile and inverted triangle column wings. Furthermore, HPLC-ELSD analysis of these three species revealed the interesting chemotaxonomic difference that the principle and characteristic lactone glycoside in this new species was kinsenoside, rather than its diastereoisomer, goodyeroside A, a major glycoside in A.zhejiangensis and A.malipoensis.

15.
Animals (Basel) ; 13(22)2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38003147

RESUMO

The A. japonicus industry has expanded significantly, but no research has focused on determining the age of A. japonicus during farming. Correctly estimating the age of A. japonicus can provide a decision-making basis for the breeding process and data for the protection of A. japonicus aquatic germplasm resources. DNA methylation levels in the body wall of Apostichopus japonicus at 4 months, 1 year, 2 years, and 3 years old were determined using MethylRAD-Seq, and differentially methylated genes were screened. A total of 441 and 966 differentially methylated genes were detected at the CCGG and CCWGG sites, respectively. Aspartate aminotransferase, succinate semialdehyde dehydrogenase, isocitrate dehydrogenase, the histone H2AX, heat shock protein Hsp90, aminopeptidase N, cell division cycle CDC6, Ras GTPase activating protein (RasGAP), slit guidance ligand slit1, integrin-linked kinase ILK, mechanistic target of rapamycin kinase Mtor, protein kinase A Pka, and autophagy-related 3 atg3 genes may play key roles in the growth and aging process of A. japonicus. This study provides valuable information regarding age-related genes for future research, and these candidate genes can be used to create an "epigenetic clock".

16.
Bioinformatics ; 39(11)2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37971954

RESUMO

MOTIVATION: In the medical field, multiple terminology bases coexist across different institutions and contexts, often resulting in the presence of redundant terms. The identification of overlapping terms among these bases holds significant potential for harmonizing multiple standards and establishing unified framework, which enhances user access to comprehensive and well-structured medical information. However, the majority of terminology bases exhibit differences not only in semantic aspects but also in the hierarchy of their classification systems. The conventional approaches that rely on neighborhood-based methods such as GCN may introduce errors due to the presence of different superordinate and subordinate terms. Therefore, it is imperative to explore novel methods to tackle this structural challenge. RESULTS: To address this heterogeneity issue, this paper proposes a multi-view alignment approach that incorporates the hierarchical structure of terminologies. We utilize BERT-based model to capture the recursive relationships among different levels of hierarchy and consider the interaction information of name, neighbors, and hierarchy between different terminologies. We test our method on mapping files of three medical open terminologies, and the experimental results demonstrate that our method outperforms baseline methods in terms of Hits@1 and Hits@10 metrics by 2%. AVAILABILITY AND IMPLEMENTATION: The source code will be available at https://github.com/Ulricab/Bert-Path upon publication.


Assuntos
Software , Vocabulário Controlado , Semântica , Benchmarking , Padrões de Referência
17.
Int J Mol Sci ; 24(17)2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37686435

RESUMO

Vanillin holds significant importance as a flavoring agent in various industries, including food, pharmaceuticals, and cosmetics. The CoA-dependent pathway for the biosynthesis of vanillin from ferulic acid involved feruloyl-CoA synthase (Fcs) and enoyl-CoA hydratase/lyase (Ech). In this research, the Fcs and Ech were derived from Streptomyces sp. strain V-1. The sequence conservation and structural features of Ech were analyzed by computational techniques including sequence alignment and molecular dynamics simulation. After detailed study for the major binding modes and key amino acid residues between Ech and substrates, a series of mutations (F74W, A130G, A130G/T132S, R147Q, Q255R, ΔT90, ΔTGPEIL, ΔN1-11, ΔC260-287) were obtained by rational design. Finally, the yield of vanillin produced by these mutants was verified by whole-cell catalysis. The results indicated that three mutants, F74W, Q147R, and ΔN1-11, showed higher yields than wild-type Ech. Molecular dynamics simulations and residue energy decomposition identified the basic residues K37, R38, K561, and R564 as the key residues affecting the free energy of binding between Ech and feruloyl-coenzyme A (FCA). The large changes in electrostatic interacting and polar solvating energies caused by the mutations may lead to decreased enzyme activity. This study provides important theoretical guidance as well as experimental data for the biosynthetic pathway of vanillin.


Assuntos
Liases , Enoil-CoA Hidratase/genética , Benzaldeídos , Aminoácidos
18.
Chiropr Man Therap ; 31(1): 27, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37563732

RESUMO

BACKGROUND: In this retrospective study, we aimed to develop a nomogram to predict recurrence during a 1-year period of spinal manipulation/mobilization (SM/M) in patients with low back pain (LBP) with greater pain intensity, more severe comorbid conditions, or a neuropathic component. METHODS: A total of 786 consecutive patients with LBP treated with SM/M as primary therapy were divided into training (n = 545) and validation (n = 241) sets. Cox regression analyses were used to assess the relative value of clinical factors and lumbar magnetic resonance imaging features associated with recurrence during the 1-year period. Predictors of recurrence with significant differences were used to construct a nomogram in the training set. We evaluated the performance of the model on the training and validation sets to determine its discriminative ability, calibration, and clinical utility. The prognostic value of the nomogram for predicting recurrence was assessed using Kaplan-Meier analysis and time-dependent receiver operating characteristic analyses. RESULTS: A nomogram comprising hospitalization time, previous history of LBP, disease duration, lumbar range of motion, lower extremity tendon reflex, muscle strength, ratio of herniation to uncompressed dural sac area, and Pfirrmann classification was established for recurrence during a 1-year period after SM/M in patients with LBP. Favorable calibration and discrimination were observed in the nomogram training and validation sets (C-index 0.753 and 0.779, respectively). Decision curve analysis confirmed the clinical utility of the nomogram. Over a 1-year period, the nomogram showed satisfactory performance in predicting recurrence in LBP after SM/M. CONCLUSION: We established and validated a novel nomogram that can accurately predict a patient's risk of LBP recurrence following SM/M. This realistic prognostic model may aid doctors and therapists in their decision-making process and strategy optimization for non-surgical treatment of LBP using SM/M.


Assuntos
Dor Lombar , Manipulação da Coluna , Humanos , Dor Lombar/diagnóstico por imagem , Dor Lombar/terapia , Nomogramas , Estudos Retrospectivos , Região Lombossacral
19.
Proc Natl Acad Sci U S A ; 120(35): e2304112120, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37607236

RESUMO

Wnt signaling plays an essential role in developmental and regenerative myelination in the central nervous system. The Wnt signaling pathway is composed of multiple regulatory layers; thus, how these processes are coordinated to orchestrate oligodendrocyte (OL) development remains unclear. Here, we show CK2α, a Wnt/ß-catenin signaling Ser/Thr kinase, phosphorylates Daam2, inhibiting its function and Wnt activity during OL development. Intriguingly, we found Daam2 phosphorylation differentially impacts distinct stages of OL development, accelerating early differentiation followed by decelerating maturation and myelination. Application toward white matter injury revealed CK2α-mediated Daam2 phosphorylation plays a protective role for developmental and behavioral recovery after neonatal hypoxia, while promoting myelin repair following adult demyelination. Together, our findings identify a unique regulatory node in the Wnt pathway that regulates OL development via protein phosphorylation-induced signaling complex instability and highlights a new biological mechanism for myelin restoration.


Assuntos
Substância Branca , Fosforilação , Bainha de Mielina , Via de Sinalização Wnt
20.
Bioengineered ; 14(1): 2180221, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37489712

RESUMO

Rapid laboratory detection is remarkably crucial to diagnosing coronavirus disease 2019 (COVID-19) infection, due to whose outbreak causes to the world pandemic. The BinaxNOW antigen card (BinaxNOW) is a simple, effective, and cheap tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The meta-analysis in this study was conducted to evaluate the diagnostic performance of BinaxNOW for SARS-CoV-2. The researchers independently retrieved the related databases (PubMed, Embase, Web of Science, Cochrane Library) before May 1st, 2021, and extracted the relevant data based on the early inclusion/exclusion criterion. Quality Assessment of Diagnostic Accuracy Study-2 was used to evaluate the quality of the enrolled studies. Stata 16.0, Meta-DiSc 1.4, and Review Manager 5.3 were used to generate analytical data for the statistical analysis. 59 sets of data were identified from the seven studies included in this meta-analysis. The combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and their 95% confidence intervals were 0.77 (0.76 to 0.79), 0.99 (0.99 to 0.99), 65.72 (48.23 to 89.56), 0.23 (0.19 to 0.28), and 461.10 (281.55 to 755.13), respectively. The area under curve was 0.9910 in the summary receiver operating characteristic curve. BinaxNOW is beneficial for symptomatic patients' onset within 7 days. CT value and testing site may be the heterogeneity source of BinaxNOW accuracy. Moreover, this technology has an efficient performance for diagnosing COVID-19, especially in patients with heavy viral load. BinaxNOW may become a practical tool for large-scale or at-home use for COVID-19 in the post-pandemic era.Highlights● Pooled sensitivity with 0.77 and specificity with 0.99 in the BinaxNOW assay.● CT value and testing site may be the heterogeneity source of BinaxNOW accuracy.● BinaxNOW is beneficial for symptomatic patients' onset within 7 days.● BinaxNOW may become a practical tool for large-scale or at-home use for COVID-19.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Bases de Dados Factuais , Razão de Chances , Pandemias , Teste para COVID-19
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