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1.
MedComm (2020) ; 5(9): e716, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39224539

RESUMEN

The challenge of disease relapsed/refractory (R/R) remains a therapeutic hurdle in chimeric antigen receptor (CAR) T-cell therapy, especially for hematological diseases, with chronic lymphocytic leukemia (CLL) being particularly resistant to CD19 CAR T cells. Currently, there is no approved CAR T-cell therapy for CLL patients. In this study, we aimed to address this unmet medical need by choosing the B-cell activating factor receptor (BAFF-R) as a promising target for CAR design against CLL. BAFF-R is essential for B-cell survival and is consistently expressed on CLL tumors. Our research discovered that BAFF-R CAR T-cell therapy exerted the cytotoxic effects on both CLL cell lines and primary B cells derived from CLL patients. In addition, the CAR T cells exhibited cytotoxicity against CD19-knockout CLL cells that are resistant to CD19 CAR T therapy. Furthermore, we were able to generate BAFF-R CAR T cells from small blood samples collected from CLL patients and then demonstrated the cytotoxic effects of these patient-derived CAR T cells against autologous tumor cells. Given these promising results, BAFF-R CAR T-cell therapy has the potential to meet the long-standing need for an effective treatment on CLL patients.

2.
Front Nutr ; 11: 1438941, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39234292

RESUMEN

Disease-related malnutrition is a prevalent issue among cancer patients, affecting approximately 40-80% of those undergoing treatment. This condition is associated with numerous adverse outcomes, including extended hospitalization, increased morbidity and mortality, delayed wound healing, compromised muscle function and reduced overall quality of life. Moreover, malnutrition significantly impedes patients' tolerance of various cancer therapies, such as surgery, chemotherapy, and radiotherapy, resulting in increased adverse effects, treatment delays, postoperative complications, and higher referral rates. At present, numerous countries and regions have developed objective assessment models to predict the risk of malnutrition in cancer patients. As advanced technologies like artificial intelligence emerge, new modeling techniques offer potential advantages in accuracy over traditional methods. This article aims to provide an exhaustive overview of recently developed models for predicting malnutrition risk in cancer patients, offering valuable guidance for healthcare professionals during clinical decision-making and serving as a reference for the development of more efficient risk prediction models in the future.

3.
Int J Mol Sci ; 25(17)2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39273486

RESUMEN

Vanda R.Br. is an epiphytic orchid genus with significant horticultural and ornamental value. Previous molecular studies expanded Vanda including some members from five other genera. However, the interspecific relationships of this recently radiated genus have remained unclear based on several DNA markers until now. In this study, the complete plastome has been used to infer the phylogenetic relationships of Vanda s.l. The five newly obtained plastomes ranged from 146,340 bp to 149,273 bp in length, with a GC content ranging from 36.5% to 36.7%. The five plastomes contained 74 protein-coding genes (CDSs), 38 tRNAs, and 8 rRNAs, and their ndh genes underwent loss or pseudogenization. Comparative plastome analyses of 13 Vanda species revealed high conservation in terms of genome size, structure, and gene order, except for a large inversion from trnGGCC to ycf3 in V. coerulea. Moreover, six CDSs and five non-CDSs were selected as candidate DNA barcodes. Our phylogenetic analyses demonstrated that Vanda s.l. is a monophyletic group with high supporting values based on five different datasets (complete plastome with one IR, 68 CDSs, LSC, five hypervariable non-CDSs, and six hypervariable CDSs), while the phylogenetic relationships among species were fully resolved based on the complete plastome with one IR dataset. Our results confirmed that the complete plastome has a great power in resolving the phylogenetic relationships of recently radiated lineages.


Asunto(s)
Evolución Molecular , Orchidaceae , Filogenia , Orchidaceae/genética , Orchidaceae/clasificación , Genoma de Plastidios , Composición de Base , Código de Barras del ADN Taxonómico
4.
Environ Sci Technol ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39258979

RESUMEN

The escalating utilization of carbon dots (CDs) in agriculture raises ecological concerns. However, their combined toxicity with arsenic remains poorly understood. Herein, we investigated the combined mitochondrial genotoxicity of CDs and arsenate at environmentally relevant concentrations across successive earthworm generations. Iron-doped CDs (CDs-Fe) strongly bound to arsenate and arsenite, while nitrogen-doped CDs (CDs-N) exhibited weaker binding. Both CDs enhanced arsenate bioaccumulation without affecting its biotransformation, with most arsenate being reduced to arsenite. CDs-Fe generated significantly more reactive oxygen species than did CDs-N, causing stronger mitochondrial DNA (mtDNA) damage. Arsenate further exacerbated the oxidative mtDNA damage induced by CDs-N, as evidenced by increased reactive oxygen species, elevated 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG) levels, and a higher correlation between 8-OHdG and mtDNA damage. This was due to arsenic inhibiting the antioxidant enzyme catalase. This exacerbation was negligible with CDs-Fe because their strong binding with arsenic prevented catalase inhibition. Maternal mitochondrial DNA damage was inherited by filial earthworms, which experienced significant weight loss in coexposure groups coupled with mtDNA toxicity. This study reveals the synergistic genotoxicity of CDs and arsenate, suggesting that CDs could disrupt the arsenic biogeochemical cycle, increase arsenate risk to terrestrial animals, and influence ecosystem stability and health through multigenerational impacts.

5.
Bioresour Technol ; 413: 131436, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39245064

RESUMEN

Glycyrrhetinicacid (GA) is a high-value pentacyclic triterpenoid with broad applications. However, the industrial production of GA is hindered by low yield and the accumulation of the intermediate product GlycyrrhetinicAcid3-O-Mono-ß-D-Glucuronide (GAMG). This study first identified a novel ß-glucuronidase (AcGUS) from Aspergillus calidoustus CLH-22 through transcriptomic analysis, demonstrating a substrate preference for GAMG. Subsequently, mutant AcGUS3G461C/Q462H/I575K with significantly improved activity (kcat/Km of 11.02-fold) was obtained via computer-aided engineering. Furthermore, the dual-GUS combination strategy was employed for the first timeto construct engineered Pichia pastoris for GA production, offering multiple advantages of enhanced conversion efficiency and reduced fermentation viscosity. Finally, under systematically optimized conditions and employing Glycyrrhizin (GL) as the substrate, the final concentration of GA was 48.73 g/L with a conversion of 97.26 % in a 1000-L fermenter, representing the optimal biocatalytic performance reported to date. This study provides new ideas and insights for industrial GA production.

6.
J Ovarian Res ; 17(1): 182, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39252114

RESUMEN

BACKGROUND: There has been a significant surge in animal studies of stem cell-derived extracellular vesicles (EVs) therapy for the treatment of premature ovarian failure (POF) but its efficacy remains unknown and a comprehensive and up-to-date meta-analysis is lacking. Before clinical translation, it is crucial to thoroughly understand the overall impact of stem cell-derived EVs on POF. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science were searched up to February 18, 2024. The risk of bias was evaluated according to Cochrane Handbook criteria, while quality of evidence was assessed using the SYRCLE system. The PRISMA guidance was followed. Trial sequential analysis was conducted to assess outcomes, and sensitivity analysis and publication bias analysis were performed using Stata 14. RESULTS: Data from 25 studies involving 339 animals were extracted and analyzed. The analysis revealed significant findings: stem cell-derived EVs increase ovary weight (SMD = 3.88; 95% CI: 2.50 ~ 5.25; P < 0.00001; I2 = 70%), pregnancy rate (RR = 3.88; 95% CI: 1.94 ~ 7.79; P = 0.0001; I2 = 0%), count of births (SMD = 2.17; 95% CI: 1.31 ~ 3.04; P < 0.00001; I2 = 69%) and counts of different types of follicles. In addition, it elevates the level of AMH (SMD = 4.15; 95% CI: 2.75 ~ 5.54; P < 0.00001; I2 = 88%) and E2 (SMD = 2.88; 95% CI: 2.02 ~ 3.73; P < 0.00001; I2 = 80%) expression, while reducing FSH expression (SMD = -5.05; 95% CI: -6.60 ~ -3.50; P < 0.00001; I2 = 90%). Subgroup analysis indicates that the source of EVs, animal species, modeling method, administration route, and test timepoint affected efficacy. Trial sequential analysis showed that there was sufficient evidence to confirm the effects of stem cell-derived EVs on birth counts, ovarian weights, and follicle counts. However, the impact of stem cell-derived EVs on pregnancy rates needs to be further demonstrated through more animal experimental evidence. CONCLUSIONS: Stem cell-derived EVs demonstrate safety and efficacy in treating POF animal models, with potential improvements in fertility outcomes. TRIAL REGISTRATION: PROSPERO registration number: CRD42024509699.


Asunto(s)
Vesículas Extracelulares , Insuficiencia Ovárica Primaria , Femenino , Insuficiencia Ovárica Primaria/terapia , Insuficiencia Ovárica Primaria/metabolismo , Vesículas Extracelulares/metabolismo , Animales , Células Madre/metabolismo , Ovario/metabolismo , Humanos , Embarazo , Modelos Animales de Enfermedad
7.
Front Mol Neurosci ; 17: 1399965, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39169951

RESUMEN

Human apolipoprotein E (ApoE) was first identified as a polymorphic gene in the 1970s; however, the genetic association of ApoE genotypes with late-onset sporadic Alzheimer's disease (sAD) was only discovered 20 years later. Since then, intensive research has been undertaken to understand the molecular effects of ApoE in the development of sAD. Despite three decades' worth of effort and over 10,000 papers published, the greatest mystery in the ApoE field remains: human ApoE isoforms differ by only one or two amino acid residues; what is responsible for their significantly distinct roles in the etiology of sAD, with ApoE4 conferring the greatest genetic risk for sAD whereas ApoE2 providing exceptional neuroprotection against sAD. Emerging research starts to point to a novel and compelling hypothesis that the sialoglycans posttranslationally appended to human ApoE may serve as a critical structural modifier that alters the biology of ApoE, leading to the opposing impacts of ApoE isoforms on sAD and likely in the peripheral systems as well. ApoE has been shown to be posttranslationally glycosylated in a species-, tissue-, and cell-specific manner. Human ApoE, particularly in brain tissue and cerebrospinal fluid (CSF), is highly glycosylated, and the glycan chains are exclusively attached via an O-linkage to serine or threonine residues. Moreover, studies have indicated that human ApoE glycans undergo sialic acid modification or sialylation, a structural alteration found to be more prominent in ApoE derived from the brain and CSF than plasma. However, whether the sialylation modification of human ApoE has a biological role is largely unexplored. Our group recently first reported that the three major isoforms of human ApoE in the brain undergo varying degrees of sialylation, with ApoE2 exhibiting the most abundant sialic acid modification, whereas ApoE4 is the least sialylated. Our findings further indicate that the sialic acid moiety on human ApoE glycans may serve as a critical modulator of the interaction of ApoE with amyloid ß (Aß) and downstream Aß pathogenesis, a prominent pathologic feature in AD. In this review, we seek to provide a comprehensive summary of this exciting and rapidly evolving area of ApoE research, including the current state of knowledge and opportunities for future exploration.

8.
Hellenic J Cardiol ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39147094

RESUMEN

OBJECTIVE: The benefits of rhythm control in early atrial fibrillation (AF) are increasingly recognized. This study aimed to investigate whether early AF ablation contributes to long-term sinus rhythm maintenance and to identify a suitable predictive score. METHODS: According to diagnosis-to-ablation time, this study prospectively enrolled 245 patients with very early AF, 262 with early AF, and 588 with late AF for radiofrequency ablation from June 2017 to December 2022. Clinical data, risk scores, and follow-up results were collected and analyzed. RESULTS: Baseline characteristics were similar among the three cohorts. During a median follow-up period of 26 months, AF recurrence was observed in 61 (24.9%), 66 (25.2%), and 216 (36.7%) patients in the very early, early, and late AF cohorts, respectively. In the multivariable-adjusted model, very early and early AF were associated with a reduced risk of AF recurrence, with hazard ratios of 0.72 (95% confidence interval [CI] 0.52-0.99) and 0.57 (95% CI 0.41-0.78), respectively. The APPLE score demonstrated the highest predictive power for very early AF, with an area under the curve (AUC) of 0.74. However, its predictive power decreased with time from diagnosis, showing low predictive power for late AF (AUC = 0.58). In addition, the time-dependent concordance index showed consistent results. For very early AF, the Akaike information criterion and decision curve analysis showed that APPLE had the highest predictive value. CONCLUSION: Very early AF ablation was associated with a lower recurrence rate, and the APPLE score provided a higher predictive value for these patients. (URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR-OIN-17013021).

9.
Int J Mol Sci ; 25(15)2024 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-39126069

RESUMEN

Gastrochilus is an orchid genus containing about 70 species in tropical and subtropical Asia with high morphological diversity. The phylogenetic relationships among this genus have not been fully resolved, and the plastome evolution has not been investigated either. In this study, five plastomes of Gastrochilus were newly reported, and sixteen plastomes of Gastrochilus were used to conduct comparative and phylogenetic analyses. Our results showed that the Gastrochilus plastomes ranged from 146,183 to 148,666 bp, with a GC content of 36.7-36.9%. There were 120 genes annotated, consisting of 74 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. No contraction and expansion of IR borders, gene rearrangements, or inversions were detected. Additionally, the repeat sequences and codon usage bias of Gastrochilus plastomes were highly conserved. Twenty hypervariable regions were selected as potential DNA barcodes. The phylogenetic relationships within Gastrochilus were well resolved based on the whole plastome, especially among main clades. Furthermore, both molecular and morphological data strongly supported Haraella retrocalla as a member of Gastrochilus (G. retrocallus).


Asunto(s)
Código de Barras del ADN Taxonómico , Evolución Molecular , Orchidaceae , Filogenia , Orchidaceae/genética , Orchidaceae/clasificación , Código de Barras del ADN Taxonómico/métodos , Genoma de Plastidios
10.
BMC Vet Res ; 20(1): 353, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39118061

RESUMEN

In recent years, dental implants have become a trend in the treatment of human patients with missing teeth, which may also be an acceptable method for companion animal dentistry. However, there is a gap challenge in determining appropriate implant sizes for different dog breeds and human. In this study, we utilized skull computed tomography data to create three-dimensional models of the mandibles of dogs in different sizes. Subsequently, implants of various sizes were designed and subjected to biomechanical finite element analysis to determine the optimal implant size. Regression models were developed, exploring the relationship between the average weight of dogs and the size of premolar implants. Our results illustrated that the regression equations for mean body weight (x, kg) and second premolar (PM2), third premolar (PM3), and fourth premolar (PM4) implant length (y, mm) in dogs were: y = 0.2785x + 7.8209, y = 0.2544x + 8.9285, and y = 0.2668x + 10.652, respectively; the premolar implant diameter (mm) y = 0.0454x + 3.3506, which may provide a reference for determine suitable clinical implant sizes for dogs.


Asunto(s)
Diente Premolar , Implantes Dentales , Análisis de Elementos Finitos , Mandíbula , Animales , Perros , Tomografía Computarizada por Rayos X/veterinaria , Implantación Dental/métodos , Implantación Dental/veterinaria , Masculino , Femenino , Predicción
11.
Viruses ; 16(8)2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39205306

RESUMEN

Severe fever with thrombocytopenia syndrome virus (SFTSV), also known as the Dabie Banda virus, is an emerging tick-borne Bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS). Currently, symptomatic treatment and antiviral therapy with ribavirin and favipiravir are used in clinical management. However, their therapeutical efficacy is hardly satisfactory in patients with high viral load. In this study, we explored the antiviral effects of selective estrogen receptor modulators (SERMs) on SFTSV infection and the antiviral mechanisms of a representative SERM, bazedoxifene acetate (BZA). Our data show that SERMs potently inhibited SFTSV-induced cytopathic effect (CPE), the proliferation of infectious viral particles, and viral RNA replication and that BZA effectively protected mice from lethal viral challenge. The mode of action analysis reveals that BZA exerts antiviral effects during the post-entry stage of SFTSV infection. The transcriptome analysis reveals that GRASLND and CYP1A1 were upregulated, while TMEM45B and TXNIP were downregulated. Our findings suggest that SERMs have the potential to be used in the treatment of SFTSV infection.


Asunto(s)
Antivirales , Phlebovirus , Moduladores Selectivos de los Receptores de Estrógeno , Síndrome de Trombocitopenia Febril Grave , Replicación Viral , Animales , Antivirales/farmacología , Antivirales/uso terapéutico , Phlebovirus/efectos de los fármacos , Ratones , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Síndrome de Trombocitopenia Febril Grave/tratamiento farmacológico , Síndrome de Trombocitopenia Febril Grave/virología , Replicación Viral/efectos de los fármacos , Humanos , Chlorocebus aethiops , Femenino , Línea Celular , Células Vero , Modelos Animales de Enfermedad
12.
Cardiovasc Diabetol ; 23(1): 291, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39113032

RESUMEN

BACKGROUND: Atrial fibrillation (AF) is acknowledged as a disease continuum. Despite catheter ablation being recommended as a primary therapy for AF, the high recurrence rates have tempered the initial enthusiasm. Insulin resistance (IR) has been established as an independent predictor for the onset of AF. However, the correlation between non-insulin-based IR indices and late AF recurrence in patients undergoing radiofrequency catheter ablation remains unknown. METHODS: A retrospective cohort of 910 AF patients who underwent radiofrequency catheter ablation was included in the analysis. The primary endpoint was late AF recurrence during the follow-up period after a defined blank period. The relationship between non-insulin-based IR indices and the primary endpoint was assessed using multivariate Cox hazards regression models and restricted cubic splines (RCS). Additionally, the net reclassification improvement and integrated discrimination improvement index were calculated to further evaluate the additional predictive value of the four IR indices beyond established risk factors for the primary outcome. RESULTS: During a median follow-up period of 12.00 months, 189 patients (20.77%) experienced late AF recurrence, which was more prevalent among patients with higher levels of IR. The multivariate Cox hazards regression analysis revealed a significant association between these IR indices and late AF recurrence. Among the four indices, METS-IR provided the most significant incremental effect on the basic model for predicting late AF recurrence. Multivariable-adjusted RCS curves illustrated a nonlinear correlation between METS-IR and late AF recurrence. In subgroup analysis, METS-IR exhibited a significant correlation with late AF recurrence in patients with diabetes mellitus (HR: 1.697, 95% CI 1.397 - 2.063, P < 0.001). CONCLUSION: All the four non-insulin-based IR indices were significantly associated with late AF recurrence in patients undergoing radiofrequency catheter ablation. Addressing IR could potentially serve as a viable strategy for reducing the late AF recurrence rate.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Resistencia a la Insulina , Recurrencia , Humanos , Fibrilación Atrial/cirugía , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Masculino , Femenino , Ablación por Catéter/efectos adversos , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Anciano , Factores de Tiempo , Medición de Riesgo , Resultado del Tratamiento , Biomarcadores/sangre , Valor Predictivo de las Pruebas , Glucemia/metabolismo
13.
Virol Sin ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39168248

RESUMEN

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus that causes the severe fever thrombocytopenia syndrome, which manifests as fever and haemorrhage, accompanied by severe neurological complications. To date, no specific antiviral drugs have been approved for this indication. Herein, we investigated whether vitamin D derivatives inhibit SFTSV both in vitro and in vivo. An in vitro study demonstrated that vitamin D derivatives significantly suppressed viral RNA replication, plaque formation, and protein expression in a dose-dependent manner. Subsequently, in vivo studies revealed that doxercalciferol and alfacalcidol were associated with increased survival and reduced viral RNA load in the blood. Time-of-addition assay suggested that vitamin D derivatives primarily acted during the post-entry phase of SFTSV infection. However, cytopathic effect protective activity was not observed in RIG-I immunodeficient cell line Huh7.5, and the administration of vitamin D derivatives did not improve the survival rates or reduce the blood viral loads in adult A129 mice. Further transcriptome exploration into the antiviral mechanism revealed that alfacalcidol stimulates host innate immunity to exert antiviral effects. To expand the application of vitamin D derivatives, in vitro and in vivo drug combination assays were performed, which highlighted the synergistic effects of vitamin D derivatives and T-705 on SFTSV. The combination of alfacalcidol and T-705 significantly enhanced the therapeutic effects in mice. This study highlights the potential of vitamin D derivatives against SFTSV and suggests that they may have synergistic effects with other compounds used in the treatment of SFTSV infection.

14.
Otol Neurotol ; 45(9): 985-992, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39207313

RESUMEN

BACKGROUND: To prospectively evaluate the technical efficacy and safety of the double-lumen eustachian tube (ET) balloon catheter in patients with ET dysfunction. METHODS: Patients who were diagnosed with ET dysfunction and needed balloon eustachian tuboplasty (BET) were prospectively enrolled. A double-lumen ET balloon catheter was used to dilate the ET and inject medicine. Efficacy results were assessed by the injection channel patency (ICP) rate, the injection reached the expected site (IRES) rate, and the improvement in eustachian tube function was evaluated by the seven-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) score. Safety results were assessed in terms of adverse events and device defects. RESULTS: BET was successfully attempted in 87 patients from April 2022 to August 2022 at two academic medical centers in China (01, 02). The ICP rate was 100%, and the IRES rate was 88.51%. The overall ETDQ-7 score was significantly reduced ( p < 0.001) postsurgically at both centers. There were no major complications or device defects. CONCLUSION: The double-lumen ET balloon catheter is technically effective and safe for the treatment of ET dysfunction.


Asunto(s)
Enfermedades del Oído , Trompa Auditiva , Humanos , Trompa Auditiva/cirugía , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Prospectivos , Enfermedades del Oído/cirugía , Resultado del Tratamiento , Anciano , Catéteres , Cateterismo/métodos , Cateterismo/instrumentación , Adulto Joven , Dilatación/instrumentación , Dilatación/métodos
15.
Front Vet Sci ; 11: 1394814, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39132438

RESUMEN

Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) is regarded as one of the most important priority pathogens within the One Health interface. However, few studies have investigated the occurrence of ESBL-EC in giant pandas, along with their antibiotic-resistant characteristics and horizontal gene transfer abilities. In this study, we successfully identified 12 ESBL-EC strains (8.33%, 12/144) out of 144 E. coli strains which isolated from giant pandas. We further detected antibiotic resistance genes (ARGs), virulence-associated genes (VAGs) and mobile genetic elements (MGEs) among the 12 ESBL-EC strains, and the results showed that 13 ARGs and 11 VAGs were detected, of which bla CTX-M (100.00%, 12/12, with 5 variants observed) and papA (83.33%, 10/12) were the most prevalent, respectively. And ISEcp1 (66.67%, 8/12) and IS26 (66.67%, 8/12) were the predominant MGEs. Furthermore, horizontal gene transfer ability analysis of the 12 ESBL-EC showed that all bla CTX-M genes could be transferred by conjugative plasmids, indicating high horizontal gene transfer ability. In addition, ARGs of rmtB and sul2, VAGs of papA, fimC and ompT, MGEs of ISEcp1 and IS26 were all found to be co-transferred with bla CTX-M. Phylogenetic analysis clustered these ESBL-EC strains into group B2 (75.00%, 9/12), D (16.67%, 2/12), and B1 (8.33%, 1/12), and 10 sequence types (STs) were identified among 12 ESBL-EC (including ST48, ST127, ST206, ST354, ST648, ST1706, and four new STs). Our present study showed that ESBL-EC strains from captive giant pandas are reservoirs of ARGs, VAGs and MGEs that can co-transfer with bla CTX-M via plasmids. Transmissible ESBL-EC strains with high diversity of resistance and virulence elements are a potential threat to humans, animals and surrounding environment.

16.
Aging Dis ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39133904

RESUMEN

Despite substantial evidence highlighting molecular communication within the components of neurovascular units (NVU), the interactions at the organelle level have been insufficiently explored in recent decades. Mitochondria, for instance, beyond their traditional role as energy supply for intracellular metabolism and survival, provide a novel perspective on intercellular connections through mitochondrial transfer. These transferred mitochondria not only carry bioactive molecules but also signal to mitigate risks in both healthy and pathological conditions. In this review, we summarized mitochondrial transfer events, relevant routes, and underlying molecular mechanisms originating from diverse cell populations within NVU. We particularly focus on the therapeutic potential of this mechanism in treating central nervous system disorders, notably neurodegenerative diseases marked by mitochondrial dysfunction and then highlight the promising prospects of exogenous mitochondrial supplementation as a treatment target.

17.
BMC Health Serv Res ; 24(1): 1005, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39210305

RESUMEN

BACKGROUND: Medical corporations, which are non-profit organizations that aim to operate hospitals, clinics, or long-term care facilities, account for more than half of all hospital beds and play a central role in the health care system in Japan. However, limited analysis of hospital integration has been performed. Examining the hospital integration trends of medical corporations can provide valuable insights for optimizing health care delivery and resource allocation in Japan. This study conducted a comprehensive analysis of trends in the hospital integration of medical corporations and market concentration in Japan using nationwide longitudinal data. METHODS: This longitudinal study evaluated the hospital integration of medical corporations in Japan between 2017 and 2021 using medical corporation financial data provided by the Neostage Company. The target population was medical corporations that own hospitals in Japan. The primary outcomes were the horizontal and vertical integration of medical corporation hospitals. Horizontal integration was defined as the integration of two or more hospitals within the same corporation, while vertical integration was defined as the integration of a hospital with different types of health care facilities, such as clinics or long-term care facilities, within a single medical corporation. The Herfindahl-Hirschman Index (HHI) was calculated to measure hospital market concentration using hospital bed data for medical corporations in all prefectures. RESULTS: The number of hospitals and hospital beds within medical corporations decreased from 5,670 to 848,174 in 2017 to 5,486 and 814,462 in 2021, respectively. Both horizontal and vertical integration among medical corporation facilities showed a gradual upward trend, increasing from 24.92% to 55.75% in 2017 to 26.92% and 59.42% in 2021, respectively. The mean (standard deviation [SD]) HHI increased slightly from 262.7 (178.6) in 2017 to 275.2 (187.9) in 2021, with rural areas being more concentrated than urban areas, although both remained unconcentrated. CONCLUSIONS: This longitudinal study revealed a gradual downward trend in the number of hospitals and hospital beds owned by medical corporations, while horizontal and vertical integration gradually progressed without any particular medical corporation dominating the market. These findings are expected to contribute to policymaking efforts aimed at providing optimal health care services in Japan.


Asunto(s)
Hospitales , Organizaciones sin Fines de Lucro , Japón , Estudios Longitudinales
18.
Med Phys ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39088754

RESUMEN

BACKGROUND: When applied to thermoacoustic imaging (TAI), the delay-and-sum (DAS) algorithm produces strong sidelobes due to its disadvantages of uniform aperture weighting. As a result, the quality of TAI images recovered by DAS is often severely degraded by strong non-coherent clutter, which restricts the development and application of TAI. PURPOSE: To address this issue, we propose an adaptive complementary neighboring sub-aperture (NSA) beamforming algorithm for TAI. METHODS: In NSA, we introduce a coordinate system transformation when calculating the normalized cross-correlation (NCC) matrix. This approach enables the computation of the NCC coefficient within the specified kernel without complex coordinate calculations. We first conducted the numerical simulation experiment to validate NSA using a tree branch phantom. In addition, we also conducted phantom (five sauce tubes), ex vivo (ablation needle in ex vivo porcine liver), and in vivo (human arm) TAI experiments using our TAI system with a center frequency of 3 GHz. RESULTS: In the numerical simulation experiment, the structural similarity index (SSIM) value for NSA is increased from 0.37828 for DAS to 0.75492. In the point target phantom TAI experiment, the generalized contrast-to-noise ratio (gCNR) value for NSA is increased from 0.936 for DAS to 0.962. The experimental results show that NSA can recover clearer thermoacoustic images compared to DAS. In the ex vivo TAI experiment, the full width at half maxima (FWHM) of an ablation needle (diameter = 1.5 mm) for coherence factor (CF) weighted DAS and NSA are 0.9 and 1.3 mm, respectively. Furthermore, in the in vivo TAI experiment, CF reduces the signals within the arm compared to NSA. Therefore, compared with CF, NSA can maintain the integrity of target information in TAI while effectively suppressing non-coherent background clutter. CONCLUSIONS: NSA can effectively reduce non-coherent background noise while ensuring the completeness of the target information. So, NSA offers the potential to provide high-quality thermoacoustic images and further advance their clinical application.

19.
J Vasc Access ; : 11297298241258793, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39097788

RESUMEN

BACKGROUND: The possibility of creating an arteriovenous fistula (AVF) depends on the existence of an arterial-venous network that is in good condition, defined by the size and elasticity of the blood vessels. The knowledge, attitudes, and practices (KAP) toward vascular protection play a crucial role in preserving the vascular network for patients with end-stage renal disease (ESRD), it is observed that there is a significant lack of tools to measure these variables. Thus, the aim of this study is to develop and validate a scale to assess KAP regarding vascular protection anticipatory to the creation of an arteriovenous fistula (the KAP-VPAC-AVF Scale). METHODS: Initial item development was guided by a literature review and clinical experience, after which the items were improved and perfected through the Delphi process. The content of the scale was judged by an expert panel for content validity. In a convenience sample of 551 patients with ESRD, exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to examine the instrument's factor structure. RESULTS: The KAP-VPAC-AVF Scale encompasses 11 items distributed over three factors: knowledge, attitude, and practice, demonstrated excellent internal consistency (Cronbach's alpha = 0.917) and construct validity, as confirmed by CFA with satisfactory fit indices (χ2/df = 2.394, RMSEA = 0.075, RMR = 0.049, CFI = 0.969, GFI = 0.936, AGFI = 0.892, TLI = 0.957, IFI = 0.970). CONCLUSION: The KAP-VPAC-AVF Scale is a scientific and effective assessment tool that can evaluate the KAP of ESRD patients regarding measures to preserve the vascular network.

20.
Environ Sci Technol ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39138130

RESUMEN

The synthesis of polycyclic aromatic hydrocarbon (PAH) data allows us to quantify and gain insights into the spatiotemporal dynamics of PAH contamination in marine bays. Here, a data synthesis framework was developed to understand data-driven insights into the spatiotemporal levels, compositional profiles, and potential sources of PAHs in water and sediment of marine bays. PAHs were detected in 69 bays worldwide, with contamination hotspots located in Asian bays. PAH concentrations in pre-2000 were significantly lower than those in the 2000s and post-2010, while the dominant species in water and sediment were 2-3 ring and 4-6 ring PAHs, respectively. The composition patterns of PAHs included 2-3 ring, 3-5 ring, and 4-5 ring dominant categories, but no significant distance decay relationship was found in the composition similarity due to international energy trade. Temporal dynamic patterns of concentrations included Descending-, Ascending-, and Inverted V-type, whereas over longer time spans, the pattern is more similar to the Inverted V-type owing to the reductions in emission intensity. PAHs were derived from both petrogenic and pyrolytic sources, with combustion from both coal and petroleum being the dominant source. These data-driven discoveries provide quantitative insights into the spatiotemporal patterns in the concentration and composition of PAHs, contributing to the mitigation of PAH contamination.

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