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The strong anti-inflammatory effect of methylprednisolone (MP) is a necessary treatment for various severe cases including acute spinal cord injury (SCI). However, concerns have been raised regarding adverse effects from MP, which also severely limits its clinical application. Natural polyphenols, due to their rich phenolic hydroxyl chemical properties, can form dynamic structures without additional modification, achieving targeted enrichment and drug release at the disease lesion, making them a highly promising carrier. Considering the clinical application challenges of MP, a natural polyphenolic platform is employed for targeted and efficient delivery of MP, reducing its systemic side effects. Both in vitro and SCI models demonstrated polyphenols have multiple advantages as carriers for delivering MP: (1) Achieved maximum enrichment at the injured site in 2 h post-administration, which met the desires of early treatment for diseases; (2) Traceless release of MP; (3) Reducing its side effects; (4) Endowed treatment system with new antioxidative properties, which is also an aspect that needs to be addressed for diseases treatment. This study highlighted a promising prospect of the robust delivery system based on natural polyphenols can successfully overcome the barrier of MP treatment, providing the possibility for its widespread clinical application.
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AIM: The main focus of this study is to explore the molecular mechanism of IRF7 regulation on RPS18 transcription in M1-type macrophages in pancreatic adenocarcinoma (PAAD) tissue, as well as the transfer of RPS18 by IRF7 via exosomes to PAAD cells and the regulation of ILF3 expression. METHODS: By utilising single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics (ST) data from the Gene Expression Omnibus database, we identified distinct cell types with significant expression differences in PAAD tissue. Among these cell types, we identified those closely associated with lipid metabolism. The differentially expressed genes within these cell types were analysed, and target genes relevant to prognosis were identified. Flow cytometry was employed to assess the expression levels of target genes in M1 and M2 macrophages. Cell lines with target gene knockout were constructed using CRISPR/Cas9 editing technology, and cell lines with target gene knockdown and overexpression were established using lentiviral vectors. Additionally, a co-culture model of exosomes derived from M1 macrophages with PAAD cells was developed. The impact of M1 macrophage-derived exosomes on the lipid metabolism of PAAD cells in the model was evaluated through metabolomics analysis. The effects of M1 macrophage-derived exosomes on the viability, proliferation, division, migration and apoptosis of PAAD cells were assessed using MTT assay, flow cytometry, EdU assay, wound healing assay, Transwell assay and TUNEL staining. Furthermore, a mouse PAAD orthotopic implantation model was established, and bioluminescence imaging was utilised to assess the influence of M1 macrophage-derived exosomes on the intratumoural formation capacity of PAAD cells, as well as measuring tumour weight and volume. The expression of proliferation-associated proteins in tumour tissues was examined using immunohistochemistry. RESULTS: Through combined analysis of scRNA-seq and ST technologies, we discovered a close association between M1 macrophages in PAAD samples and lipid metabolism signals, as well as a negative correlation between M1 macrophages and cancer cells. The construction of a prognostic risk score model identified RPS18 and IRF7 as two prognostically relevant genes in M1 macrophages, exhibiting negative and positive correlations, respectively. Mechanistically, it was found that IRF7 in M1 macrophages can inhibit the transcription of RPS18, reducing the transfer of RPS18 to PAAD cells via exosomes, consequently affecting the expression of ILF3 in PAAD cells. IRF7/RPS18 in M1 macrophages can also suppress lipid metabolism, cell viability, proliferation, migration, invasion and intratumoural formation capacity of PAAD cells, while promoting cell apoptosis. CONCLUSION: Overexpression of IRF7 in M1 macrophages may inhibit RPS18 transcription, reduce the transfer of RPS18 from M1 macrophage-derived exosomes to PAAD cells, thereby suppressing ILF3 expression in PAAD cells, inhibiting the lipid metabolism pathway, and curtailing the viability, proliferation, migration, invasion of PAAD cells, as well as enhancing cell apoptosis, ultimately inhibiting tumour formation in PAAD cells in vivo. Targeting IRF7/RPS18 in M1 macrophages could represent a promising immunotherapeutic approach for PAAD in the future.
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Factor 7 Regulador del Interferón , Metabolismo de los Lípidos , Macrófagos , Neoplasias Pancreáticas , Análisis de la Célula Individual , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Metabolismo de los Lípidos/genética , Macrófagos/metabolismo , Factor 7 Regulador del Interferón/genética , Factor 7 Regulador del Interferón/metabolismo , Humanos , Análisis de la Célula Individual/métodos , Ratones , Animales , Línea Celular TumoralRESUMEN
The pathogenesis of osteoarthritis (OA) involves a multifaceted interplay of inflammatory processes. The initiation of pyroptosis involves the secretion of pro-inflammatory cytokines and has been identified as a critical factor in regulating the development of OA. Upon initiation of pyroptosis, a multitude of inflammatory mediators are released and can be disseminated throughout the synovial fluid within the joint cavity, thereby facilitating intercellular communication across the entire joint. The main cellular components of joints include chondrocytes (CC), fibroblast-like synoviocytes (FLS) and macrophages (MC). Investigating their interplay can enhance our understanding of OA pathogenesis. Therefore, we comprehensively examine the mechanisms underlying pyroptosis and specifically investigate the intercellular interactions associated with pyroptosis among these three cell types, thereby elucidating their collective contribution to the progression of OA. We propose the concept of ' CC-FLS-MC pyroptosis-related crosstalk', describe the various pathways of pyroptotic interactions among these three cell types, and focus on recent advances in intervening pyroptosis in these three cell types for treating OA. We hope this will provide a possible direction for diversification of treatment for OA. The Translational potential of this article. The present study introduces the concept of 'MC-FLS-CC pyroptosis-related crosstalk' and provides an overview of the mechanisms underlying pyroptosis, as well as the pathways through which it affects MC, FLS, and CC. In addition, the role of regulation of these three types of cellular pyroptosis in OA has also been concerned. This review offers novel insights into the interplay between these cell types, with the aim of providing a promising avenue for diversified management of OA.
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Serratia sp. ATCC 39006 is an important model strain for the study of prodigiosin production, whose prodigiosin biosynthesis genes (pigA-O) are arranged in an operon. Several transcription factors have been shown to control the transcription of the pig operon. However, since the regulation of prodigiosin biosynthesis is complex, the regulatory mechanism for this process has not been well established. In most γ-proteobacteria, the ROK family regulator NagC acts as a global transcription factor in response to N-acetylglucosamine (GlcNAc). In Serratia sp. ATCC 39006, NagC represses the transcription of two divergent operons, nagE and nagBAC, which encode proteins involved in the transport and metabolism of GlcNAc. Moreover, NagC directly binds to a 21-nt region that partially overlaps the -10 and -35 regions of the pig promoter and promotes the transcription of prodigiosin biosynthesis genes, thereby increasing prodigiosin production. Although NagC still acts as both repressor and activator in Serratia sp. ATCC 39006, its transcriptional regulatory activity is independent of GlcNAc. NagC was first found to regulate antibiotic biosynthesis in Gram-negative bacteria, and NagC-mediated regulation is not responsive to GlcNAc, which contributes to future studies on the regulation of secondary metabolism by NagC in other bacteria. IMPORTANCE: The ROK family transcription factor NagC is an important global regulator in the γ-proteobacteria. A large number of genes involved in the transport and metabolism of sugars, as well as those associated with biofilm formation and pathogenicity, are regulated by NagC. In all of these regulations, the transcriptional regulatory activity of NagC responds to the supply of GlcNAc in the environment. Here, we found for the first time that NagC can regulate antibiotic biosynthesis, whose transcriptional regulatory activity is independent of GlcNAc. This suggests that NagC may respond to more signals and regulate more physiological processes in Gram-negative bacteria.
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Acetilglucosamina , Proteínas Bacterianas , Regulación Bacteriana de la Expresión Génica , Prodigiosina , Serratia , Serratia/genética , Serratia/metabolismo , Prodigiosina/biosíntesis , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Acetilglucosamina/metabolismo , Operón , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
INTRODUCTION: With the continuous advancement of medical imaging, 3D printing technology is emerging. This technology allows for the representation of complex objects in a model form. This research aims to delve into the irreplaceable value of percutaneous nephrolithotomy (PCNL) in conjunction with 3D printed models in urinary stone surgery. This forward-looking approach provides doctors with a new perspective, enabling them to plan and execute surgeries with greater precision, ultimately delivering a safer and more efficient treatment experience for patients. We evaluated the literature on PCNL for the kidney stones with the introduction of 3D printing models and conducted a meta-analysis. The assessed parameters included stone clearance rate, operation time, hospital stay, blood loss, puncture accuracy, and the rate of complications. EVIDENCE ACQUISITION: We systematically searched the EMBASE, PubMed, Cochrane Library, SCIE, and Chinese Biomedical Literature Search databases for articles related to PCNL (Percutaneous Nephrolithotomy) with 3D printing models from January 2000 to January 2023. Data were managed and screened using Excel . Meta-analysis was performed for operation time, stone clearance rate, blood loss, puncture accuracy, length of hospital stay, and complications in PCNL combined with 3D printing model for kidney stone treatment. The quality of included articles was assessed using the risk of bias tool by the Cochrane Collaboration. Sensitivity analysis was conducted to assess the reliability of the results. Data were recorded using StataSE 17 software, and publication bias was examined using Egger's linear regression test. EVIDENCE SYNTHESIS: We followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to conduct a systematic search and screening of literature relevant to the use of 3D printed models in the treatment of kidney stones. We conducted an extensive literature search across several major academic databases, including EMBASE, PubMed, Cochrane Library, SCIE, and Chinese Biomedical Literature Search databases, to ensure comprehensive coverage of relevant studies. Following the PRISMA process of screening and analysis, we ultimately included 10 randomized controlled trials with a combined sample of 608 for systematic review. CONCLUSIONS: Across these studies, we identified the introduction of 3D printing models prior to surgery for kidney stones resulted in significant advantages for the experimental group compared to the control group in terms of operation time, stone clearance rates, puncture accuracy, hospital stay, blood loss, and the incidence of complications, providing valuable insights for further research and clinical practice.
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Cálculos Renales , Nefrolitotomía Percutánea , Impresión Tridimensional , Humanos , Nefrolitotomía Percutánea/métodos , Nefrolitotomía Percutánea/efectos adversos , Cálculos Renales/cirugía , Modelos AnatómicosRESUMEN
Although functional studies on carbohydrate-binding module (CBM) have been carried out extensively, the role of tandem CBMs in the enzyme containing multiple catalytic domains (CDs) is unclear. Here, we identified a multidomain enzyme (Lc25986) with a novel modular structure from lignocellulolytic bacterial consortium. It consists of a mannanase domain, two CBM65 domains (LcCBM65-1/LcCBM65-2), and an esterase domain. To investigate CBM function and domain interactions, full-length Lc25986 and its variants were constructed and used for enzymatic activity, binding, and bioinformatic analyses. The results showed that LcCBM65-1 and LcCBM65-2 both bind mannan and xyloglucan but not cellulose or ß-1,3-1,4-glucan, which differs from the ligand specificity of reported CBM65s. Compared to LcCBM65-2, LcCBM65-1 showed a stronger ligand affinity and a preference for acetylation sites. Both CBM65s stimulated the enzymatic activities of their respective neighboring CDs against acetylated mannan, but did not contribute to the activities of the distal CDs. The time course of mannan hydrolysis indicated that the full-length Lc25986 was more effective in the complete degradation of mixed acetyl/non-acetyl substrates than the mixture of single-CD mutants. When acting on complex substrates, LcCBM65-1 not only improved the enzymatic activity of the mannanase domain, but also directed the esterase domain to the acetylated polysaccharides. LcCBM65-2 adopted a low affinity to reduce interference with the catalysis of the mannanase domain. These results demonstrate the importance of CBMs for the synergism between the two CDs of a multidomain enzyme and suggest that they contribute to the adequate degradation of complex substrates such as plant cell walls. IMPORTANCE: Lignocellulolytic enzymes, particularly those of bacterial origin, often harbor multiple carbohydrate-binding modules (CBMs). However, the function of CBM multivalency remains poorly understood. This is especially true for enzymes that contain more than one catalytic domain (CD), as the interactions between CDs, CBMs, and CDs and CBMs can be complex. Our research demonstrates that homogeneous CBMs can have distinct functions in a multimodular enzyme. The tandem CBMs coordinate the CDs in catalytic conflict through their differences in binding affinity, ligand preference, and arrangement within the full-length enzyme. Additionally, although the synergism between mannanase and esterase is widely acknowledged, our study highlights the benefits of integrating the two enzymes into a single entity for the degradation of complex substrates. In summary, these findings enhance our understanding of the intra-synergism of a multimodular enzyme and emphasize the significance of multiple CBMs in this context.
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Proteínas Bacterianas , Dominio Catalítico , Glucanos , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Glucanos/metabolismo , Xilanos/metabolismo , Mananos/metabolismo , Lignina/metabolismo , Bacterias/enzimología , Bacterias/genética , Hidrólisis , Especificidad por SustratoRESUMEN
BACKGROUND: The pathogenesis of thyroid-associated orbitopathy (TAO) remains incompletely understand. The interaction between immunocytes and orbital fibroblasts (OFs) play a critical role in orbital inflammatory and fibrosis. Accumulating reports indicate that a significant portion of plasma exosomes (Pla-Exos) are derived from immune cells; however, their impact upon OFs function is unclear. METHODS: OFs were primary cultured from inactive TAO patients. Exosomes isolated from plasma samples of patients with active TAO and healthy controls (HCs) were utilized for functional and RNA cargo analysis. Functional analysis in thymocyte differentiation antigen-1+ (Thy-1+) OFs measured expression of inflammatory and fibrotic markers (mRNAs and proteins) and cell activity in response to Pla-Exos. RNA cargo analysis was performed by RNA sequencing and RT-qPCR. Thy-1+ OFs were transfected with miR-144-3p mimics/inhibitors to evaluate its regulation of inflammation, fibrosis, and proliferation. RESULTS: Pla-Exos derived from active TAO patients (Pla-ExosTAO-A) induced stronger production of inflammatory cytokines and hyaluronic acid (HA) in Thy-1+ OFs while inhibiting their proliferation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and single sample gene set enrichment analysis (ssGSEA) suggested that the difference in mRNA expression levels between Pla-ExosTAO-A and Pla-ExosHC was closely related to immune cells. Differential expression analysis revealed that 62 upregulated and 45 downregulated miRNAs in Pla-ExosTAO-A, with the elevation of miR-144-3p in both Pla-Exos and PBMCs in active TAO group. KEGG analysis revealed that the target genes of differentially expressed miRNA and miR-144-3p enriched in immune-related signaling pathways. Overexpression of the miR-144-3p mimic significantly upregulated the secretion of inflammatory cytokines and HA in Thy-1+ OFs while inhibiting their proliferation. CONCLUSION: Pla-Exos derived from patients with active TAO were immune-active, which may be a long-term stimulus casual for inflammatory and fibrotic progression of TAO. Our finding suggests that Pla-Exos could be used as biomarkers or treatment targets in TAO patients.
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Exosomas , Fibroblastos , Fibrosis , Oftalmopatía de Graves , Inflamación , MicroARNs , Órbita , Humanos , Exosomas/metabolismo , Oftalmopatía de Graves/patología , Oftalmopatía de Graves/sangre , Oftalmopatía de Graves/genética , MicroARNs/genética , MicroARNs/metabolismo , MicroARNs/sangre , Fibroblastos/metabolismo , Fibroblastos/patología , Órbita/patología , Inflamación/patología , Femenino , Masculino , Proliferación Celular , Persona de Mediana Edad , Adulto , Ácido Hialurónico/sangre , Ácido Hialurónico/metabolismo , Citocinas/metabolismo , Antígenos Thy-1/metabolismoRESUMEN
Orthogonal frequency division multiplexing (OFDM) utilizes numerous sub-carriers to achieve high transmission data rates. The frequency selectivity of the channel becomes a crucial factor influencing the communication performance of OFDM-based systems. In optical wireless communication (OWC) systems, the photomultiplier tube (PMT) may experience saturation when the incident optical power approaches its saturation threshold. This paper, for the first time, characterizes the saturation levels of a high-speed PMT based on the measured amplitude in the time domain and the output response of the PMT in the frequency domain. Additionally, an adaptive optical saturation compensation algorithm, leveraging an electronically controlled variable optical attenuator, is proposed to realize a reliable OWC system. Experimental results demonstrate that the proposed saturation compensation method achieves a higher tolerance to large dynamic signal and background radiation compared with that without compensation, while maintaining a satisfactory bit error rate.
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A co-frequency and full-duplex (FD) underwater optical wireless communication (UOWC) system has the potential to significantly enhance spectral efficiency, reduce complexity, and further facilitate UOWC networking. However, the inevitable performance degradation due to self-interference introduced by backscattering presents a significant challenge. In this paper, we first experimentally explore the inherent characteristics of the underwater backscattering channel. Subsequently, we propose a digital-domain backscattering interference cancellation (BIC) algorithm for FD-UOWC systems, incorporating a time-reversal preprocessing. We then experimentally investigate the communication performance of an FD-UOWC system to verify the feasibility of the proposed BIC algorithm under different channel conditions. The experimental results validate the effectiveness of the proposed method, yielding substantial enhancements in bit error rate performance across diverse scenarios.
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Nucleotide second messengers are highly versatile signaling molecules that regulate a variety of key biological processes in bacteria. The best-studied examples are cyclic AMP (cAMP) and bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP), which both act as global regulators. Global regulatory frameworks of c-di-GMP and cAMP in bacteria show several parallels but also significant variances. In this review, we illustrate the global regulatory models of the two nucleotide second messengers, compare the different regulatory frameworks between c-di-GMP and cAMP, and discuss the mechanisms and physiological significance of cross-regulation between c-di-GMP and cAMP. c-di-GMP responds to numerous signals dependent on a great number of metabolic enzymes, and it regulates various signal transduction pathways through its huge number of effectors with varying activities. In contrast, due to the limited quantity, the cAMP metabolic enzymes and its major effector are regulated at different levels by diverse signals. cAMP performs its global regulatory function primarily by controlling the transcription of a large number of genes via cAMP receptor protein (CRP) in most bacteria. This review can help us understand how bacteria use the two typical nucleotide second messengers to effectively coordinate and integrate various physiological processes, providing theoretical guidelines for future research.
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Arthroscopic repair of Bankart injury is the first choice for the treatment of anterior shoulder instability. How to avoid recurring shoulder joint dislocation is a challenge, especially when combined with Hill-Sachs lesions. The arthroscopy technology allows for broader vision and less surgical trauma but is limited by a smaller operating space. At present, extensive descriptions about the surgical procedure of arthroscopic Bankart repair have been published. In this Technical Note, we describe the use of remplissage filling with Hill-Sachs lesion combined with Bankart repair to further improve the surgical accuracy and clinical efficacy. In particular, the application of single needle-assisted outside-in remplissage technique and Bankart repair is introduced in detail.
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Self-excited combustion instability in an annular combustor with low-swirl flames is studied with a combination of large eddy simulation (LES) and acoustic solvers. Acoustic analysis with a Helmholtz solver provides an estimate of frequencies and modal structures in the annular combustor. LES gives detailed modal dynamics for specific instability modes. Combustion instabilities in the annular combustor including longitudinal, spinning, and standing modes are successfully captured in a single LES. Numerical results show that the instability modes are not constant; they switch among these modes randomly and rapidly. The flow oscillates back and forth in phase with the largest pressure amplitude located near the outlet of the injectors for the longitudinal mode. The azimuthal instability oscillates in the 1A2L mode of the annular system. In the spinning mode, the pressure antinodes move forward while the modal structure keeps constant. For the standing mode, the locations of pressure antinodes are fixed in the annular combustor and the fluctuations at the pressure antinodes keep out of phase. The near-zero value of the mean spin ratio indicates that the dominant azimuthal mode is the standing mode. The azimuthal modes captured by LES are in good agreement with that predicted by Helmholtz solver in terms of frequency and modal structure. The maximum deviation of the predicted frequency is less than 5%. This adds values before the low-swirl injector is placed into the actual annular combustor.
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Objective: The study aims to analyze the clinical characteristics of acute phase of SARS-CoV-2 infection in children aged 0-17 years with the Omicron variant, and summarize the persistent symptoms or new-onset clinical manifestations from 4 to 12 weeks after acute COVID. Explore the association between the vaccination status and SARS-CoV-2 neutralizing antibody levels post infection among preschool-aged children. The comprehensive study systematically describes the clinical characteristics of children infected with SARS-CoV-2, providing a foundation for diagnosis and evaluating long-term COVID in pediatric populations. Methods: The study enrolled children who were referred to the Children's Hospital, Capital Institute of Pediatrics, (Beijing, China) from January 10, 2023 to March 31, 2023. Participants were classified as infant and toddlers, preschool, school-age, and adolescent groups. Children or their legal guardians completed survey questionnaires to provide information of previous SARS-CoV-2 infection history, as well as clinical presentation during the acute phase and long-term symptoms from 4 to 12 weeks following infection. Furthermore, serum samples were collected from children with confirmed history of SARS-CoV-2 infection for serological testing of neutralizing antibodies. Results: The study recruited a total of 2,001 children aged 0-17 years who had previously tested positive for SARS-CoV-2 through nucleic acid or antigen testing. Fever emerged as the predominant clinical manifestation in 1,902 (95.1%) individuals with body temperature ranging from 37.3 to 40.0°C. Respiratory symptoms were identified as secondary clinical manifestations, with cough being the most common symptom in 777 (38.8%) children, followed by sore throat (22.1%), nasal congestion (17.8%), and runnning nose (17.2%). Fatigue (21.6%), headache (19.8%) and muscle-joint pain (13.5%) were frequently reported systemic symptoms in children. The proportion of children with symptoms of SARS-CoV-2 infection varied across age groups. 1,100 (55.0%) children experienced persistent symptoms from 4 to 12 weeks post the acute phase of infection. Trouble concentrating (22.1%), cough (22.1%), and fatigue (12.1%) were frequently reported across age groups in the extended period. A limited number of children exhibited cardiovascular symptoms with chest tightness, tachycardia, and chest pain reported by 3.5%, 2.5%, and 1.8% of children, respectively. Among 472 children aged 3-5 years, 208 children had received two doses of SARS-CoV-2 vaccine at least 6 months prior to infection, and no association was found between the incidence of long-term COVID and pre-infection vaccination statuses among the 3-5 years age groups (χ2 = 1.136, P = 0.286). Conclusions: In children aged 0-17 years infected with SARS-CoV-2 Omicron variant, fever was the primary clinical manifestation in the acute phase, followed by respiratory symptoms, systemic non-specific and digestive presentations. In particular, respiratory and digestive system symptoms were more frequent in children aged above 6 years. Regarding the long-term symptoms from 4 to 12 weeks post-infection, the most common presentations were concentrating difficulty, cough, and fatigue. The incidence of persistent symptoms of SARS-CoV-2 did not exhibit a significant correlation with vaccination status, which was attributed to the waning efficacy of the vaccine-induced humoral immune response after 6 months.
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Modulating the electrical properties of two-dimensional (2D) materials is a fundamental prerequisite for their development to advanced electronic and optoelectronic devices. Substitutional doping has been demonstrated as an effective method for tuning the band structure in monolayer 2D materials. Here, we demonstrate a facile selective-area growth of vanadium-doped molybdenum disulfide (V-doped MoS2) flakes via pre-patterned vanadium-metal-assisted chemical vapor deposition (CVD). Optical microscopy characterization revealed the presence of flake arrays. Transmission electron microscopy, Raman spectroscopy, and X-ray photoelectron spectroscopy were employed to identify the chemical composition and crystalline structure of as-grown flakes. Electrical measurements indicated a light p-type conduction behavior in monolayer V-doped MoS2. Furthermore, the response time of phototransistors based on V-doped MoS2 monolayers exhibited a remarkable capability of 3 ms, representing approximately 3 orders of magnitude faster response than that observed in pure MoS2 phototransistors. This work hereby provides a feasible approach to doping of 2D materials, promising a scalable pathway for the integration of these materials into emerging electronic and optoelectronic devices.
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BACKGROUND: Degenerative meniscal tear (DMT) is common in the elderly population. However, there has been controversy over the treatment of DMT regarding whether to adopt arthroscopic partial meniscectomy (APM) or exercise therapy (ET). In order to compare the long-term outcomes between the two treatment methods, we conducted a meta-analysis of randomized controlled trials (RCTs) with long-term follow-up. METHODS: PubMed, Cochrane Library, Embase, and Web of Science were last searched on 16 April 2023 for studies on DMT that compared the clinical outcomes between APM and ET. The subjective outcomes of the comparison include the Knee Injury and Osteoarthritis Outcome Score (KOOS), which consists of five sub-scales: pain, symptoms, activities of daily living (ADL), sport and recreation (Sport/recreation), and quality of life (QOL). The objective outcome includes knee osteoarthritis progression. RESULTS: We identified 6 potentially eligible trials, including 1078 participants, from the literature search. ET showed a lower risk of knee osteoarthritis progression than APM (RR, 1·27; 95%CI 1·05 to 1·53). There were no statistically significant differences in the KOOS-pain, KOOS-symptoms, KOOS-ADL, KOOS-Sport/recreation, and KOOS-QOL between the two treatment methods. CONCLUSION: For the treatment of DMT, ET showed a lower risk of knee osteoarthritis progression than APM. ET and APM had comparable effects on subjective outcomes including pain management and knee function. Therefore, it is not recommended to use APM but rather recommended to use ET for treating APM.
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Terapia por Ejercicio , Meniscectomía , Osteoartritis de la Rodilla , Lesiones de Menisco Tibial , Humanos , Actividades Cotidianas , Artroscopía/métodos , Progresión de la Enfermedad , Terapia por Ejercicio/métodos , Estudios de Seguimiento , Meniscectomía/métodos , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/terapia , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Lesiones de Menisco Tibial/cirugía , Lesiones de Menisco Tibial/terapia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: There was controversy surrounding the optimal thromboprophylaxis strategy for coronavirus disease 2019 (COVID-19) patients. This included debates on the dosage of anticoagulants for thromboembolism prophylaxis, the requirement for additional antiplatelet therapy, and the necessity of prophylaxis for outpatients and postdischarge. To explore this, the authors performed a meta-analysis of randomized controlled trials. METHODS: PubMed, Cochrane Library, Embase, and Web of Science were last searched on 26 July 2023 for studies comparing the effect of different dose of anticoagulation, additional antiplatelet, and postdischarge prophylaxis for COVID-19 patients. The results of eligible studies were analyzed in terms of thromboembolism events, major bleeding and all-cause mortality during follow-up. RESULTS: Our study included a total of 25 randomized controlled trials, involving 17 911 patients. Our results revealed that, compared to prophylactic dose, therapeutic dose showed lower thrombotic risk (RR, 0.66; 95% CI: 0.45-0.96) but had similar major bleeding risk for critically ill patients with COVID-19. On the other hand, intermediate dose and prophylactic dose demonstrated similar thromboembolism risk and major bleeding risk. For noncritically ill patients with COVID-19, therapeutic dose of anticoagulants was associated with lower thrombotic risk (RR, 0.50; 95% CI: 0.34-0.72) but, at the same time, increased the risk of major bleeding (RR, 2.01; 95% CI: 1.22-3.33). However, intermediate dose showed lower thromboembolism risk (RR, 0.38; 95% CI: 0.21-0.69) while maintaining a similar major bleeding risk. In critically ill patients, additional antiplatelet therapy showed similar thromboembolism, major bleeding risk, and mortality when compared to no treatment. For outpatients, additional prophylactic anticoagulation showed similar thromboembolism, major bleeding risk, and mortality when compared to no treatment. For postdischarge patients, postdischarge prophylaxis reduced thromboembolism risk (RR, 0.49; 95% CI: 0.31-0.76) but increased major bleeding risk (RR, 2.63; 95% CI: 1.13-6.14). CONCLUSION: For noncritically ill patients, therapeutic dose prophylactic anticoagulation significantly reduced venous thromboembolism but increases major bleeding risk. Intermediate dose effectively lowered venous thromboembolism without raising major bleeding risk. The optimal dose and need for additional antiplatelet therapy in critically ill patients, as well as the necessity of prophylactic anticoagulation in outpatient and postdischarge patients, required further investigation and confirmation through rigorous evidence studies.
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Anticoagulantes , COVID-19 , Inhibidores de Agregación Plaquetaria , Ensayos Clínicos Controlados Aleatorios como Asunto , Tromboembolia , Humanos , COVID-19/prevención & control , COVID-19/complicaciones , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Tromboembolia/prevención & control , Tromboembolia/etiología , Hemorragia/inducido químicamente , Alta del Paciente , SARS-CoV-2RESUMEN
As a kind of flexible electronic device, flexible pressure sensor has attracted wide attention in medical monitoring and human-machine interaction. With the continuous deepening of research, high-sensitivity sensor is developing from single function to multi-function. However, Current multifunctional sensors lack the ability to integrate joule heating, detect sliding friction, and self-healing. Herein, a MXene/polyurethane (PU) flexible pressure sensor with a self-healing property for joule heating and friction sliding is fabricated. The MXene/PU sensitive layer with special spinosum structure is prepared by a simple spraying method. After face-to-face assembly of the sensitive layers, the MXene/PU flexible pressure sensor is obtained and showed excellent sensitivity (150.65 kPa-1), fast response/recovery speed (75.5/63.9 ms), and good stability (10 000 cycles). Based on the self-healing property of PU, the sensor also has the ability to heal after mechanical damage. In addition, the sensor realizes the joule heating function under low voltage, and has the real-time monitoring ability of sliding objects. Combined with low cost and simple manufacturing method, the multi-functional MXene/PU flexible sensor shows a wide range of application potential in human activity monitoring, thermal management, and slip recognition.
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To compared the arthroscopic capsular release (ACR) with manipulation under anaesthesia (MUA) for the surgical treatment of frozen shoulder (FS) based on postoperative outcomes and complications. PubMed, Cochrane Library, Embase, and Web of Science were searched on October 2, 2023 to retrieve eligible studies that compared ACR with MUA in terms of clinical outcomes (pain visual analogue scale, external rotation, forward flexion and adverse events) for patients with FS. Mean differences (MD) were calculated for continuous outcomes and odds ratios (OR) were calculated for dichotomous outcomes. Six papers, including 5 clinical studies (a total of 690 shoulders), were included in the final meta-analysis. The forward flexion was found to be larger in the ACR group at 3 months (MD, 2.73; 95%CI, 0.42-5.04; I2 = 44%; P = 0.02) and 6 months (MD, 2.36; 95%CI, 1.29-3.44; I2 = 0%; P < 0.0001). Except for this, ACR was comparable with MUA in terms of pain visual analogue scale at 3, 6 and 12 months (p = 0.25, p = 0.11, p = 0.28, respectively), external rotation at 3, 6 and 12 months (p = 0.15, p = 0.52, p = 0.23, respectively), and forward flexion at 12 months (p = 0.08). There were no differences in complication rates between the two groups (OR, 0.82; 95%CI, 0.47-1.44; I2 = 0%; P = 0.50). In comparison with MUA, ACR demonstrated better outcomes for forward flexion at 3 and 6 months, while there were no significant differences between ACR and MUA in terms of pain visual analogue scale, external rotation and adverse events.
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We demonstrated an AlGaN-based multiple-quantum-well (MQW) deep ultraviolet (DUV) laser at 278â nm using a nanoporous (NP) n-AlGaN as the bottom cladding layer grown on the sapphire substrate. The laser has a very-low-threshold optically pumped power density of 79â kW/cm2 at room temperature and a transverse electric (TE)-polarization-dominant emission. The high optical confinement factor of 9.12% benefiting from the low refractive index of the nanoporous n-AlGaN is the key to enable a low-threshold lasing. The I-V electrical measurement demonstrates that an ohmic contact can be still achieved in the NP n-AlGaN with a larger but acceptable resistance, which indicates it is compatible with electrically driven laser devices. Our work provides insights into the design and fabrication of low-threshold lasers emitting in the DUV regime.