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1.
Int J Biol Macromol ; : 132256, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38729481

RESUMEN

Gut microbiota variances reflecting the severity type 2 diabetes mellitus (T2DM). Achyranthes bidentata polysaccharide (ABP) can regulate gut microbiota. However, the hypoglycemic effect and underlying mechanism of ABP remain unclear. Herein, we characterized the structure of ABP and revealed the hypoglycemic effect of ABP in mice with T2DM. ABP repaired the intestinal barrier in T2DM mice and regulated the composition and abundance of gut microbiota, especially increasing bacteria which producing short-chain fatty acids (SCFAs), then increasing glucagon-like peptide-1 (GLP-1) level. The abundance of these bacteria was positively correlated with blood lipid and INS levels, negatively correlated with FBG levels. Colon transcriptome data and immunohistochemistry demonstrated that the alleviating T2DM effect of ABP was related to activation of the GLP-1/GLP-1 receptor (GLP-1R)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP-response element binding protein (CREB)/INS pathway. Fecal microbiota transplantation (FMT) confirmed the transmissible efficacy of ABPs through gut microbiota. Overall, our research shows that ABP plays a hypoglycemic role by increasing gut microbiota-derived SCFAs levels, and activating the GLP-1/GLP-1R/cAMP/PKA/CREB/INS pathway, emphasizing ABP as promising T2DM therapeutic candidates.

2.
Quant Imaging Med Surg ; 14(5): 3581-3592, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38720848

RESUMEN

Background: One in four individuals with Parkinson's disease (PD) experience cognitive impairment (CI). However, few practical models integrating clinical and neuroimaging biomarkers have been developed to address CI in PD. This study aimed to evaluate the correlation between circulating neuron-specific enolase (NSE) levels, substantia nigra hyperechogenicity (SNH), and cognitive function in PD and to develop a nomogram based on clinical and neuroimaging biomarkers for predicting CI in patients with PD. Methods: A total of 385 patients with PD who underwent transcranial sonography (TCS) from January 2021 to December 2022 at Beijing Tiantan Hospital, Capital Medical University, were recruited as the training cohort. For validation, 165 patients with PD treated from January 2023 to December 2023 were enrolled. Data for SNH, plasma NSE, and other clinical measures were collected, and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Logistic regression analysis was employed to select potential risk factors and establish a nomogram. The receiver operating characteristic curve and calibration curve were generated to evaluate the performance of the nomogram. Results: Patients with PD exhibiting CI displayed advanced age, elevated Unified PD Rating Scale-III (UPDRS-III) score, an increased percentage of SNH, higher levels of plasma NSE and homocysteine (Hcy), a larger SNH area, and lower education levels compared to PD patients without CI. Gender [odds ratio (OR) =0.561, 95% confidence interval (CI): 0.330-0.954, P=0.03], age (OR =1.039; 95% CI: 1.011-1.066; P=0.005), education level (OR =0.892; 95% CI: 0.842-0.954; P<0.001), UPDRS-III scores (OR =1.026; 95% CI: 1.009-1.043; P=0.003), plasma NSE concentration (OR =1.562; 95% CI: 1.374-1.776; P<0.001), and SNH (OR =0.545; 95% CI: 0.330-0.902; P=0.02) were independent predictors of CI in patients with PD. A nomogram developed using these six factors yielded a moderate discrimination performance with an area under the curve (AUC) of 0.823 (95% CI 0.781-0.864; P<0.001). The calibration curve demonstrated acceptable agreement between predicted outcomes and actual values. Validation further confirmed the reliability of the nomogram, with an AUC of 0.864 (95% CI: 0.805-0.922; P<0.001). Conclusions: The level of NSE in plasma and the SNH assessed by TCS are associated with CI in patients with PD. The proposed nomogram has the potential to facilitate the detection of cognitive decline in individuals with PD.

3.
Aging (Albany NY) ; 162024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38709288

RESUMEN

BMP9 has demonstrated significant osteogenic potential. In this study, we investigated the effect of Leptin on BMP9-induced osteogenic differentiation. Firstly, we found Leptin was decreased during BMP9-induced osteogenic differentiation and serum Leptin concentrations were increased in the ovariectomized (OVX) rats. Both in vitro and in vivo, exogenous expression of Leptin inhibited the process of osteogenic differentiation, whereas silencing Leptin enhanced. Exogenous Leptin could increase the malonylation of ß-catenin. However, BMP9 could increase the level of Sirt5 and subsequently decrease the malonylation of ß-catenin; the BMP9-induced osteogenic differentiation was inhibited by silencing Sirt5. These data suggested that Leptin can inhibit the BMP9-induced osteogenic differentiation, which may be mediated through reducing the activity of Wnt/ß-catenin signalling via down-regulating Sirt5 to increase the malonylation level of ß-catenin partly.

4.
Small Methods ; : e2400195, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38699929

RESUMEN

Existing RNA in situ imaging strategies mostly utilize parallel repetitive nucleic acid self-assembly to achieve multiple analysis, with limitations of complicated systems and cumbersome steps. Here, a Cas9 code key system with key probe (KP) encoder and CRISPR/Cas9 signal exporter is developed. This system triggers T-protospacer adjacent motif (T-PAM structural transitions of multiple KP encoders to form coding products with uniform single-guide RNA (sgRNA) target sequences as tandem nodes. Only single sgRNA/Cas9 complex is required to cleave multiple coding products, enabling efficient "many-to-one" tandem signaling, and non-collateral cleavage activity-dependent automatic signaling output through active introduction of mismatched bases. Compared with conventional parallel multiple signaling analysis model, the proposed system greatly simplifies reaction process and enhances detection efficiency. Further, a rapid multiple RNA in situ imaging system is developed by combining the Cas9 code key system with a T-strand displacement amplification (T-SDA) signal amplifier. The constructed system is applied to tumor cells and clinicopathology slices, generating clear multi-mRNA imaging profiles in less than an hour with just one step. Therefore, this work provides reliable technical support for clinical tumor typing and molecular mechanism investigation.

5.
Mol Nutr Food Res ; 68(9): e2400048, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38659317

RESUMEN

Egg yolk lipids significantly alleviate dextran sulfate sodium (DSS)-induced colitis by inhibiting NLRP3 inflammasome, reversing gut microbiota dysbiosis, and increasing short chain fatty acids (SCFAs) concentrations. However, the role of gut microbiota and the relationship between SCFAs and NLRP3 inflammasome are still unknown. Here, this study confirms that antibiotic treatment abolishes the protective effect of egg yolk lipids on DSS-induced colonic inflammation, intestinal barrier damage, and lipopolysaccharide translocation. Fecal microbiota transplantation also supports that egg yolk lipids alleviate colitis in a gut microbiota-dependent manner. Then, the study investigates the relationship between SCFAs and NLRP3 inflammasome, and finds that SCFAs significantly suppress colitis via inhibiting colonic NLRP3 inflammasome activation and proinflammatory cytokines secretions (interleukin, IL)-1ß and IL-18, and combined treatment of SCFAs and MCC950 (NLRP3 inhibitor) shows a better activity against colitis and NLRP3 inflammasome activation. Together, these findings provide positive evidence for gut microbiorta-SCFAs-NLRP3 axis as a novel target involving in the therapy of inflammatory bowel disease.


Asunto(s)
Colitis , Sulfato de Dextran , Yema de Huevo , Ácidos Grasos Volátiles , Microbioma Gastrointestinal , Inflamasomas , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ácidos Grasos Volátiles/metabolismo , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Masculino , Ratones , Trasplante de Microbiota Fecal , Colon/efectos de los fármacos , Colon/metabolismo , Colon/microbiología , Lípidos , Interleucina-1beta/metabolismo
6.
Anal Chim Acta ; 1303: 342477, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38609257

RESUMEN

CRISPR/Cas12a-based nucleic acid assays have been increasingly used for molecular diagnostics. However, most current CRISPR/Cas12a-based RNA assays require the conversion of RNA into DNA by preamplification strategies, which increases the complexity of detection. Here, we found certain chimeric DNA-RNA hybrid single strands could activate the trans-cleavage activity of Cas12a, and then discovered the activating effect of split ssDNA and RNA when they are present simultaneously. As proof of concept, split nucleic acid-activated Cas12a (SNA-Cas12a) strategy was developed for direct detection of miR-155. By adding a short ssDNA to the proximal end of the crRNA spacer sequence, we realized the direct detection of RNA targets using Cas12a. With the assistance of ssDNA, we extended the limitation that CRISPR/Cas12a cannot be activated by RNA targets. In addition, by taking advantage of the programmability of crRNA, the length of its binding to DNA and RNA was optimized to achieve the optimal efficiency in activating Cas12a. The SNA-Cas12a method enabled sensitive miR-155 detection at pM level. This method was simple, rapid, and specific. Thus, we proposed a new Cas12a-based RNA detection strategy that expanded the application of CRISPR/Cas12a.


Asunto(s)
MicroARNs , Ácidos Nucleicos , MicroARNs/genética , Sistemas CRISPR-Cas , ARN Guía de Sistemas CRISPR-Cas , ADN de Cadena Simple/genética
7.
Theranostics ; 14(6): 2544-2559, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38646641

RESUMEN

Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin (Ctsk)-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk+ PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk+ PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Diferenciación Celular , Condrocitos , Curación de Fractura , Osteogénesis , Células Madre , Canales Catiónicos TRPP , Animales , Curación de Fractura/fisiología , Ratones , Canales Catiónicos TRPP/metabolismo , Canales Catiónicos TRPP/genética , Condrocitos/metabolismo , Células Madre/metabolismo , Osteogénesis/fisiología , Ratones Noqueados , Condrogénesis/fisiología , Periostio/metabolismo , Osteoblastos/metabolismo , Osteoblastos/fisiología , Modelos Animales de Enfermedad , Masculino
8.
PLoS One ; 19(4): e0299924, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38635814

RESUMEN

BACKGROUND: While the 23-valent pneumococcal polysaccharide vaccine (PPV23) has demonstrated its role in preventing severe pneumococcal disease, its impact on more non-specific conditions like acute respiratory tract infection (ARI) and lower respiratory tract infections (LRTI) remains unclear. We aimed to investigate the role of PPV23 in prevention of presentations for ARI and LRTI and related antibiotic prescriptions among older adults in primary care. METHODS: Using a nationwide general practice dataset, we followed a cohort of regularly attending patients aged ≥65 years from 1 January 2014 until 31 December 2018 for presentations for ARI, LRTI, and related antibiotic prescriptions. Associations between PPV23 receipt and each outcome were assessed using a multiple failures survival model to estimate hazard ratios (HR) adjusted for age, sex, socioeconomic status, and various health measures. RESULTS: A cohort of 75,264 patients aged ≥65 years (mean 75.4, 56% female) in 2014 was followed. The incidence of presentations for ARI, ARI-related antibiotic prescription, LRTI, and LRTI-related antibiotic prescription was 157.6, 76.0, 49.6, and 24.3 per 1000 person-years, respectively. Recent PPV23 vaccine receipt was associated with a small reduction in ARI presentations (adjusted HR vaccinated vs. unvaccinated 0.96; 95%CI 0.94-0.98; p = 0.002); however, there was no reduction in ARI-related antibiotic prescription, LRTI presentation, nor LRTI-related antibiotic prescription (adjusted HR were 0.99[95%CI 0.96-1.03], 1.04[95%CI 0.99-1.09], 1.07[95%CI 1.00-1.14]). CONCLUSION: PPV23 vaccination in older adults may result in a small reduction in the incidence of total ARI presentations in primary care. However, the effect is small and residual confounding cannot be excluded.


Asunto(s)
Infecciones Neumocócicas , Infecciones del Sistema Respiratorio , Humanos , Femenino , Anciano , Masculino , Antibacterianos/uso terapéutico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/prevención & control , Streptococcus pneumoniae , Vacunación , Vacunas Neumococicas/uso terapéutico , Atención Primaria de Salud , Infecciones Neumocócicas/tratamiento farmacológico , Infecciones Neumocócicas/prevención & control
9.
J Youth Adolesc ; 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38615131

RESUMEN

Parents play a crucial role in adolescents' Internet use. Both general parenting (i.e., autonomy-supportive and controlling parenting) and Internet-specific parenting (i.e., restrictive mediation, active mediation, and parental encouragement) are related to adolescents' online behaviors. However, existing studies have focused either on an Internet-specific parenting or general parenting strategy and have neglected their interaction, failing to capture the intricate nature of the parenting context of youth's online behaviors. Few studies have examined parental encouragement or acknowledged the bidirectional influence of parenting on adolescents' online behaviors. To address this gap, this study employed a cross-lagged panel network model to examine the associations among restrictive and active mediation, parental encouragement, and autonomy-supportive and controlling parenting, as well as the interplay of all five parenting strategies with adolescents' online behaviors. A total of 564 Chinese students (51.1% male; mean age = 14.54, SD = 0.7) completed the survey at two time points. The results indicate that in most cases, previous online behaviors are significant and strong predictors of subsequent parenting strategies and not vice versa, corroborating the child effect. The parent and reciprocal effects were observed in the problematic smartphone-use domain, suggesting that the effects may differ for distinct behavioral domains. The effects of parental mediation extend beyond parental encouragement, implying that risk-prevention-related parenting is an effective means of guiding adolescents' online behaviors. Autonomy-relevant general parenting is closely related to active mediation and parental encouragement, while restrictive general parenting is closely related to restrictive mediation, suggesting a consistency between Internet-specific and general parenting strategies.

10.
Mil Med Res ; 11(1): 20, 2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38556884

RESUMEN

BACKGROUND: Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury (TBI). However, the heterogeneity, multifunctionality, and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood. METHODS: Using the combined single-cell transcriptomics, metabolomics, and proteomics analysis from TBI patients and the TBI mouse model, we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests. We also characterized the underlying mechanisms both in vitro and in vivo through molecular simulations, signaling detections, gene expression regulation assessments [including dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays], primary cultures or co-cultures of neutrophils and oligodendrocytes, intracellular iron, and lipid hydroperoxide concentration measurements, as well as forkhead box protein O1 (FOXO1) conditional knockout mice. RESULTS: We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model. Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI, aggravating acute brain inflammatory damage and promoting late TBI-induced depression. In the acute stage, FOXO1 upregulated cytoplasmic Versican (VCAN) to interact with the apoptosis regulator B-cell lymphoma-2 (BCL-2)-associated X protein (BAX), suppressing the mitochondrial translocation of BAX, which mediated the antiapoptotic effect companied with enhancing interleukin-6 (IL-6) production of FOXO1high neutrophils. In the chronic stage, the "FOXO1-transferrin receptor (TFRC)" mechanism contributes to FOXO1high neutrophil ferroptosis, disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein, which contributes to the progression of late depression after TBI. CONCLUSIONS: FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI, which provides insight into the heterogeneity, reprogramming activity, and versatility of neutrophils in TBI.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Neutrófilos , Animales , Humanos , Ratones , Proteína X Asociada a bcl-2/metabolismo , Encéfalo , Lesiones Traumáticas del Encéfalo/complicaciones , Depresión , Proteína Forkhead Box O1/metabolismo , Hierro
11.
Appl Opt ; 63(10): 2570-2577, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38568538

RESUMEN

The limited excitation efficiency of quantum dots in the detection of subsurface defects in optical elements by quantum dot fluorescence gives rise to insufficient accuracy. To enhance the excitation efficiency of quantum dots, we studied the modulation of the polarization direction of linearly polarized incident light on quantum dot fluorescence. We first apply density matrix evolution theory to study the quantum dots interacting with linearly polarized incident light and emitting fluorescence. The fluorescence intensity exhibits cosine oscillations versus modulated laser polarization. It reaches a maximum value at the polarization angle zero, and then decreases as the angle becomes larger until π/2. The experimental results for the quantum dot in both solutions and subsurface defect of optical elements confirmed these results. For optical elements tagged with CdSe/ZnS quantum dots, the fluorescence intensity increases by 61.7%, and the area for the detected subsurface defects increases by 142.9%. Similarly, for C and InP/ZnS quantum dots, there are also increases in both the fluorescence intensity and the area of subsurface defects. Our study suggests that the subsurface defect detection in optical elements by the linearly polarized incident light could enhance the detection accuracy of subsurface defects in optical elements, and potentially achieve super-resolution imaging of subsurface defects.

13.
ACS Nano ; 18(17): 11389-11403, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38628141

RESUMEN

Tumor-derived extracellular vesicles (tEVs) hold immense promise as potential biomarkers for the precise diagnosis of hepatocellular carcinoma (HCC). However, their clinical translation is hampered by their inherent characteristics, such as small size and high heterogeneity and complex environment, including non-EV particles and normal cell-derived EVs, which prolong separation procedures and compromise detection accuracy. In this study, we devised a DNA cascade reaction-triggered individual EV nanoencapsulation (DCR-IEVN) strategy to achieve the ultrasensitive and specific detection of tEV subpopulations via routine flow cytometry in a one-pot, one-step fashion. DCR-IEVN enables the direct and selective packaging of multiple tEV subpopulations in clinical serum samples into flower-like particles exceeding 600 nm. This approach bypasses the need for EV isolation, effectively reducing interference from non-EV particles and nontumor EVs. Compared with conventional analytical technologies, DCR-IEVN exhibits superior efficacy in diagnosing HCC owing to its high selectivity for tEVs. Integration of machine learning algorithms with DCR-IEVN resulted in differential diagnosis accuracy of 96.7% for the training cohort (n = 120) and 93.3% for the validation cohort (n = 30), effectively distinguishing HCC, cirrhosis, and healthy donors. This strategy offers a streamlined workflow and rapid assay completion and requires only small-volume serum samples and routine clinical devices, facilitating the clinical translation of tEV-based tumor diagnosis.


Asunto(s)
Carcinoma Hepatocelular , Vesículas Extracelulares , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/sangre , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/sangre , Humanos , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Diagnóstico Diferencial , ADN/química , Biomarcadores de Tumor/sangre , Aprendizaje Automático
14.
Artículo en Inglés | MEDLINE | ID: mdl-38603541

RESUMEN

The urgent need for CO2 capture and hydrogen energy has attracted great attention owing to greenhouse gas emissions and global warming problems. Efficient CO2 capture and H2 purification with membrane technology will reduce greenhouse gas emissions and help reach a carbon-neutral society. Here, 4-sulfocalix[4]arene (SC), which has an intrinsic cavity, was embedded into the Matrimid membrane as a molecular gatekeeper for CO2 capture and H2 purification. The interactions between SC and the Matrimid polymer chains immobilize SC molecules into the interchain gaps of the Matrimid membrane, and the strong hydrogen and ionic bondings were able to form homogeneous mixed-matrix membranes. The incorporation of the SC molecular gatekeeper with exceptional molecular-sieving properties improved the gas separation performance of the mixed-matrix membranes. Compared with that of the Matrimid membrane, the CO2 permeability of the Matrimid-SC-3% membrane increased from 16.75 to 119.78 Barrer, the CO2/N2 selectivity increased from 29.39 to 106.95, and the CO2/CH4 selectivity increased from 29.91 to 140.92. Furthermore, when the permeability of H2 was increased to 172.20 Barrer, the H2/N2 and H2/CH4 selectivities reached approximately 153.75 and 202.59, respectively, which are far superior to those of most existing Matrimid-based materials. The mixed-matrix membranes also exhibited excellent long-term operation stability, with separation performance for several important gas pairs still overtaking the Robeson upper limit after aging for 400 days.

15.
Plants (Basel) ; 13(6)2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38592823

RESUMEN

The importance of rootstock in citrus production lies in its crucial role in determining tree growth, environmental stress tolerance, and fruit quality. Citrus junos Siebold ex Tanaka cv. Shuzhen No. 1, a recently developed rootstock, demonstrates excellent graft compatibility and abiotic stress tolerance. The objective of this study was to assess ten hybrid citrus cultivars grafted onto two C. junos rootstock selections, with the aim of determining the potential for industrial utilization of the new citrus rootstock. All graft junctions are mature and well established. Vigorous growth characterized all ten citrus cultivars on Shuzhen No. 1, with the largest tree's height reaching 280.33 cm (Wogan scion) and the widest scion's diameter being 67.52 cm (Chunjian scion). However, the scion-to-rootstock diameter ratio was the lowest at 0.62 (Chunxiang scion). C. junos rootstock selections significantly affected fruit weight (five of ten scions) and fruit color (seven of ten scions) but had negligible impact on peel thickness (nine of ten scions). Furthermore, rootstock type had a significant influence on fruit quality. In conclusion, our findings indicate strong graft compatibility between all scions and C. junos rootstocks, which can impact overall size and fruit quality. Based on these results, Shuzhen No. 1 is recommended as a valuable citrus rootstock.

16.
AIDS ; 38(6): 803-812, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38578958

RESUMEN

OBJECTIVES: There is conflicting data regarding the response of older people with HIV (PWH) to antiretroviral therapy (ART). The objective of this study was to evaluate the long-term immunological and virological responses, changes in regimen, and adverse drug reactions (ADRs) in older participants (50+ years) compared with younger (18-34 years) and middle-aged (35-49 years) PWH. METHODS: A retrospective review of medical records was conducted on 1622 participants who received ART in Yunnan Province, China, from 2010 to 2019. The study compared CD4+ T-cell counts, CD4+/CD8+ ratio, and relative numbers between different groups using the Kruskal-Wallis test. Cox proportional hazards regression models were used to identify variables associated with the occurrence of immune reconstitution insufficiency. The rates of immune reconstitution, incidence of ADRs, and rates of treatment change were analyzed using the chi-squared test or Fisher's exact test. RESULTS: Over 95% achieved viral load 200 copies/ml or less, with no age-related difference. However, older participants exhibited significantly lower CD4+ T-cell counts and CD4+/CD8+ recovery post-ART (P < 0.001), with only 32.21% achieving immune reconstitution (compared with young: 52.16%, middle-aged: 39.29%, P < 0.001) at the end of follow-up. Middle-aged and elderly participants changed ART regimens more because of ADRs, especially bone marrow suppression and renal dysfunction. CONCLUSION: Although the virological response was consistent across age groups, older individuals showed poorer immune responses and higher susceptibility to side effects. This underscores the need for tailored interventions and comprehensive management for older patients with HIV.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Persona de Mediana Edad , Anciano , Humanos , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/efectos adversos , China , Resultado del Tratamiento , Recuento de Linfocito CD4 , Carga Viral
17.
Biomed Environ Sci ; 37(2): 157-169, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38582978

RESUMEN

Objective: China is among the 30 countries with a high burden of tuberculosis (TB) worldwide, and TB remains a public health concern. Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China. However, molecular epidemiological studies of Kashgar are lacking. Methods: A population-based retrospective study was conducted using whole-genome sequencing (WGS) to determine the characteristics of drug resistance and the transmission patterns. Results: A total of 1,668 isolates collected in 2020 were classified into lineages 2 (46.0%), 3 (27.5%), and 4 (26.5%). The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid (7.4%, 124/1,668), streptomycin (6.0%, 100/1,668), and rifampicin (3.3%, 55/1,668). The rate of rifampicin resistance was 1.8% (23/1,290) in the new cases and 9.4% (32/340) in the previously treated cases. Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains, respectively: 18.6% vs. 8.7 or 9%, P < 0.001. The estimated proportion of recent transmissions was 25.9% (432/1,668). Multivariate logistic analyses indicated that sex, age, occupation, lineage, and drug resistance were the risk factors for recent transmission. Despite the low rate of drug resistance, drug-resistant strains had a higher risk of recent transmission than the susceptible strains (adjusted odds ratio, 1.414; 95% CI, 1.023-1.954; P = 0.036). Among all patients with drug-resistant tuberculosis (DR-TB), 78.4% (171/218) were attributed to the transmission of DR-TB strains. Conclusion: Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Rifampin/farmacología , Estudios Retrospectivos , Farmacorresistencia Bacteriana Múltiple/genética , Pruebas de Sensibilidad Microbiana , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Mutación
19.
Opt Lett ; 49(6): 1575-1578, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38489454

RESUMEN

Spatiotemporal mode-locked (STML) fiber lasers have become a new platform for investigating nonlinear phenomena. In this work, spatiotemporal dual-periodic soliton pulsation (SDSP) is firstly observed in an STML fiber laser. It is found that in the SDSP, the long-period pulsations (LPPs) of different transverse modes are synchronous, while the short-period pulsations (SPPs) exhibit asynchronous modulations. The numerical simulation confirms the experimental results and further reveals that the proportion of transverse mode components can manipulate the periods of the LPP and SPP but does not affect the synchronous and asynchronous pulsations of different transverse modes. The obtained results bring the study of spatiotemporal dissipative soliton pulsation into the multi-period modulation stage, which helps to understand the complex spatiotemporal dynamics in STML fiber lasers and discover new dynamics in high-dimensional nonlinear systems.

20.
Nat Commun ; 15(1): 2336, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38485980

RESUMEN

Quantum spin liquids (QSLs) are in a quantum disordered state that is highly entangled and has fractional excitations. As a highly sought-after state of matter, QSLs were predicted to host spinon excitations and to arise in frustrated spin systems with large quantum fluctuations. Here we report on the experimental observation and theoretical modeling of QSL signatures in monolayer 1T-NbSe2, which is a newly emerging two-dimensional material that exhibits both charge-density-wave (CDW) and correlated insulating behaviors. By using scanning tunneling microscopy and spectroscopy (STM/STS), we confirm the presence of spin fluctuations in monolayer 1T-NbSe2 by observing the Kondo resonance as monolayer 1T-NbSe2 interacts with metallic monolayer 1H-NbSe2. Subsequent STM/STS imaging of monolayer 1T-NbSe2 at the Hubbard band energy further reveals a long-wavelength charge modulation, in agreement with the spinon modulation expected for QSLs. By depositing manganese-phthalocyanine (MnPc) molecules with spin S = 3/2 onto monolayer 1T-NbSe2, new STS resonance peaks emerge at the Hubbard band edges of monolayer 1T-NbSe2. This observation is consistent with the spinon Kondo effect induced by a S = 3/2 magnetic impurity embedded in a QSL. Taken together, these experimental observations indicate that monolayer 1T-NbSe2 is a new promising QSL material.

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