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1.
Plant Cell Environ ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38946254

RESUMEN

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

2.
CNS Neurosci Ther ; 30(7): e14819, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39056208

RESUMEN

AIMS: Astrocytic senescence is inextricably linked to aging and neurodegenerative disorders, including Parkinson's disease (PD). P7C3 is a small, neuroprotective aminopropyl carbazole compound that exhibits anti-inflammatory properties. However, the effects of P7C3 on astrocytic senescence in PD remain to be elucidated. METHODS: An in vitro, long culture-induced, replicative senescence cell model and a 1-methyl-4-phenylpyridinium (MPP+)/rotenone-induced premature senescence cell model were used to investigate the effects of P7C3 on astrocytic senescence. An in vivo, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse PD model was used to study the role of P7C3 in astrocytic senescence. Immunoblotting, real-time quantitative RT-PCR (qPCR), immunofluorescence, subcellular fractionation assays, and immunohistochemistry were utilized to confirm the effects of P7C3 on astrocytic senescence and elucidate its underlying mechanisms. RESULTS: This study determined that P7C3 suppressed the senescence-associated secretory phenotype (SASP) in both cell models, as demonstrated by the reduction in the critical senescence marker p16 and proinflammatory factors (IL-6, IL-1ß, CXCL10, and MMP9) and increased laminB1 levels, implying that P7C3 inhibited replicative astrocytic senescence and MPP+/rotenone-induced premature astrocytic senescence, Most importantly, we demonstrated that P7C3 prevented the death of dopamine (DA) neurons and reduced the behavioral deficits in the MPTP-induced mouse model of PD, which is accompanied by a decrease in senescent astrocytes in the substantia nigra compacta (SNc). Mechanistically, P7C3 promoted Nrf2/Sirt3-mediated mitophagy and reduced mitochondrial reactive oxygen species (mitoROS) generation, which contributed to the suppression of astrocytic senescence. Furthermore, Sirt3 deficiency obviously abolished the inhibitory effects of P7C3 on astrocytic senescence. CONCLUSION: This study revealed that P7C3 inhibited astrocytic senescence via increased Nrf2/Sirt3-mediated mitophagy and suppression of mitoROS, which further protected against DA neuronal loss. These observations provide a prospective theoretical basis for P7C3 in the treatment of age-associated neurodegenerative diseases, such as PD.


Asunto(s)
Astrocitos , Senescencia Celular , Neuronas Dopaminérgicas , Ratones Endogámicos C57BL , Animales , Ratones , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/patología , Neuronas Dopaminérgicas/metabolismo , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Astrocitos/patología , Senescencia Celular/efectos de los fármacos , Senescencia Celular/fisiología , Masculino , Fármacos Neuroprotectores/farmacología , Carbazoles/farmacología , Modelos Animales de Enfermedad
3.
Arch Virol ; 169(8): 164, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990242

RESUMEN

Upregulation of ADAMTS-4 has been reported to have an important role in lung injury, and ADAMTS-4 expression is regulated by miR-126a-5p in abdominal aortic aneurysms. The aim of this study was to investigate whether miR-126a-5p/ADAMTS-4 plays a role in influenza-virus-induced lung injury. Lung fibroblasts were infected with H1N1 influenza virus to detect changes in miR-126a-5p and ADAMTS-4 expression, and cell viability was measured by CCK-8 assay. Inflammatory factors and matrix protease levels were examined using ELISA kits, and cell apoptosis was assessed by measuring the levels of apoptosis-related proteins. A dual luciferase assay was used to verify the regulatory relationship between miR-126a-5p and ADAMTS-4. H1N1 influenza virus reduced fibroblast viability, inhibited miR-126a-5p expression, and promoted ADAMTS-4 expression. Overexpression of miR-126a-5p attenuated the cellular inflammatory response, apoptosis, matrix protease secretion, and virus replication. Luciferase reporter assays revealed that miR-126a-5p inhibited ADAMTS-4 expression by targeting ADAMTS-4 mRNA. Further experiments showed that overexpression of ADAMTS-4 significantly reversed the inhibitory effects of miR-126a-5p on fibroblast inflammation, apoptosis, matrix protease secretion, and virus replication. Upregulation of miR-126a-5p inhibits H1N1-induced apoptosis, inflammatory factors, and matrix protease secretion, as well as virus replication in lung fibroblasts.


Asunto(s)
Proteína ADAMTS4 , Apoptosis , Fibroblastos , Inflamación , Subtipo H1N1 del Virus de la Influenza A , Pulmón , MicroARNs , MicroARNs/genética , MicroARNs/metabolismo , Fibroblastos/virología , Fibroblastos/metabolismo , Humanos , Pulmón/virología , Pulmón/patología , Proteína ADAMTS4/genética , Proteína ADAMTS4/metabolismo , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/fisiología , Inflamación/genética , Supervivencia Celular , Replicación Viral , Gripe Humana/virología , Gripe Humana/genética , Gripe Humana/metabolismo , Línea Celular
4.
Artículo en Inglés | MEDLINE | ID: mdl-39067031

RESUMEN

BACKGROUND: Arthroscopy-assisted closed reduction and percutaneous internal fixation is a minimally invasive technique for medial malleolus fracture treatment. The purpose of the study was to assess the quality and functional outcomes of this technique. METHODS: Seventy-eight patients with combined medial malleolus fractures were treated with arthroscopy-assisted closed reduction and percutaneous screw fixation technique. The surgical procedure was described in detail; the clinical efficacy of this method was evaluated in terms of time of operation, postoperative complications, and fracture healing time; and functional outcomes were analyzed. RESULTS: All of the patients were followed up for a minimum of 12 months without complications of the medial malleolus wound, and all of the medial malleolus fractures healed within 6 to 8 weeks. At the last follow-up, the visual analog scale scores ranged from 0 to 3 and the American Orthopaedic Foot and Ankle Society ankle and hindfoot function scores ranged from 75 to 95. CONCLUSIONS: Arthroscopy-assisted closed reduction and percutaneous internal fixation makes the treatment of medial malleolus fractures less invasive compared with traditional surgical methods and allows simultaneous exploration and management of the articular surface.


Asunto(s)
Fracturas de Tobillo , Artroscopía , Fijación Interna de Fracturas , Humanos , Artroscopía/métodos , Fijación Interna de Fracturas/métodos , Masculino , Fracturas de Tobillo/cirugía , Femenino , Adulto , Persona de Mediana Edad , Tornillos Óseos , Resultado del Tratamiento , Curación de Fractura/fisiología , Adulto Joven , Estudios Retrospectivos , Reducción Cerrada/métodos , Anciano , Estudios de Seguimiento , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos
5.
Analyst ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39073090

RESUMEN

To objectively quantify changes in steroid hormones in organisms caused by adverse environmental loads, we developed a simple and sensitive UPLC-MS/MS (ultra-performance liquid chromatography triple quadrupole mass spectrometry) method for the simultaneous determination of 18 steroid hormones on the HPG axis. This analytical method was based on liquid extraction and a multimode electrospray and atmospheric pressure chemical ionization (ESCi) source, which was optimized by mass spectrometry, liquid phase and pretreatment for the quantification of cholesterol (CH), aldosterone (A), cortisone (E), hydrocortisone (F), 21-deoxycortisol (21-DF), corticosterone (B), 11-deoxycortisol (11-DF), androstenedione (A2), estradiol (E2), estrone (E1), 2-methoxyestradiol (2-MeE2), 21-hydroxyprogesterone (21-OHP), 17-α hydroxyprogesterone (17α-OHP), testosterone (T), dehydroepiandrosterone (DHEA), progesterone (P4), dihydrotestosterone (DHT), and pregnenolone (P5). The method exhibits linearity in the analyte-concentration range 0.03-1000 µg mL-1 (r2 > 0.99), the spiked recoveries for the concentration range tested are 76.22-113.66%, and the relevant parameters of precision are 7.52-1.14%. Compared to other methods, this new method not only uses a small amount of serum (only 100 µL), but also permits the analysis of the challenging steroid, cholesterol. Furthermore, the method was successfully applied to the determination of steroids in Mus musculus, Carassius auratus, Rana catesbeiana Shaw, and Rana nigromaculata serum samples from randomly selected individuals. Therefore, this method is efficient and a very useful tool for assessing changes in steroid hormones.

6.
Opt Express ; 32(11): 19814-19824, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38859107

RESUMEN

The intriguing photonic spin Hall effect (PSHE) of reflected Laguerre-Gaussian (LG) beams can be exhibited on the systems with optical anti-parity-time (Anti-PT) symmetry. During the reflection, the left/right circularly polarized (LCP/RCP) components of reflected LG beams are considered. By controlling parameters of the Anti-PT systems, the PSHE of reflected LCP/RCP can be identical and symmetrical with respect to incident-reflected plane (IRP). Due to gain/non-Hermitian effects of designed Anti-PT systems, special PSHE near the strong gain points (SGP) and exceptional points (EPs) can be obtained simulatively. Through analyses in PSHE of reflected LCP on four similar Anti-PT systems, specific conclusions that can even be extended to more general cases. Moreover, simulations of PSHE by simultaneously varying the incident angles * and imaginary/real dielectric constants Im/Re[ε] of the Anti-PT systems, specal PSHE and other novel optical phenomena with real applications can be revealed. So Anti-PT systems not only provide novel ways to regulate the PSHE of reflected LG beams, but also offer possibilities for new optical characteristics of devices.

7.
Opt Express ; 32(9): 15156-15165, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38859174

RESUMEN

Fiber side-pump couplers can enhance the output power of fiber laser due to their dependable and efficient operation and impressive power handling capability. We developed a tellurite fiber side-pump coupler by twisting and fusing a tapered pump fiber onto a target fiber. The effect of twisting parameters on coupling efficiency was comprehensively investigated through theoretical simulations and experiments. Experimental results exhibited an impressive coupling efficiency of 76.5% and a root mean square stability of 0.086% and 0.091% before and after one month, respectively, driven by an incident pump power of up to 4.2 W.

8.
Chem Commun (Camb) ; 60(55): 6999-7016, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38904196

RESUMEN

Quinolines are biologically and pharmaceutically important N-heterocyclic aromatic compounds, which have broad applications in medicinal chemistry. Thus, their efficient synthesis has attracted extensive attention, and a broad range of synthetic strategies have been established. Of note, gold-catalyzed methodologies for the synthesis of quinolines have greatly advanced this field. Various gold-catalyzed intermolecular annulation reactions, such as annulations of aniline derivatives with carbonyl compounds or alkynes, annulations of anthranils with alkynes, and annulations based on A3-coupling reactions, as well as intramolecular cyclization reactions of azide-tethered alkynes, 1,2-diphenylethynes, and 2-ethynyl N-aryl indoles, have been developed. This review provides an overview of this exciting research area. Typical achievements in reaction methodologies and plausible reaction mechanisms are summarized.

9.
Lab Chip ; 24(14): 3367-3376, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38845509

RESUMEN

Point-of-care testing of "sample in, answer out" is urgently needed for communicable diseases. Recently, rapid nucleic acid tests for infectious diseases have been developed for use in resource-limited areas, but they require types of equipment in central laboratories and are poorly integrated. In this work, a portable centrifugal microfluidic testing system is developed, integrated with magnetic bead-based nucleic acid extraction, recombinase-assisted amplification and CRISPR-Cas13a detection. The system, with the advantage of its power-supplied active rotating chip and highly programable flow control through integrated addressable active thermally-triggered wax valves, has a rapid turnaround time within 45 min, requiring only one user step. All reagents are preloaded into the chip and can be automatically released. By exploiting a multichannel chip, it is capable of simultaneously detecting 10 infectious viruses with limits of detection of 1 copy per reaction and 5 copies per reaction in plasmid samples and mock plasma samples, respectively. The system was used to analyse clinical plasma samples with good consistency compared to laboratory-based molecular testing. Moreover, the generalizability of our device is reported by successfully testing nasopharyngeal swabs and whole blood samples. The portable device does not require the operation of professional technicians, making it an excellent assay for on-site testing.


Asunto(s)
Sistemas CRISPR-Cas , Dispositivos Laboratorio en un Chip , Humanos , Técnicas de Amplificación de Ácido Nucleico/instrumentación , Diseño de Equipo , Técnicas Analíticas Microfluídicas/instrumentación , Límite de Detección
10.
Microbiol Resour Announc ; 13(7): e0035724, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38898546

RESUMEN

As a noteworthy biocontrol fungus, Clonostachys chloroleuca currently lacks a high-quality reference genome. Here, we present the first high-quality genome assembly of C. chloroleuca strain Cc878 achieved through Oxford Nanopore Long-Read sequencing. The nuclear genome of Cc878 was assembled into four contigs, totaling 59.38 Mb.

11.
Biosens Bioelectron ; 261: 116505, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38885536

RESUMEN

Surface enhanced Raman spectroscopy (SERS) utilizes the fingerprint features of molecular vibrations to identify and detect substances. However, in traditional single focus excitation scenarios, its signal collection efficiency of the objective is restricted. Furthermore, the uneven distribution of samples on the SERS substrate would result in poor signal stability, while the excitation power is limited to avoid sample damage. SERS detection system always requires precise adjustment of focal length and spot size, making it difficult for point-of-care testing applications. Here, we proposed a SERS microfluidic chip with barium titanate microspheres array (BTMA) embedded using vacuum self-assembled hot-pressing method for SERS detection with simultaneous enhancement of sensitivity and stability. Due to photonic nano-jets and directional antenna effects, high index microspheres are perfect micro-lens for effective light focusing and signal collecting. The BTMA can not only disperse excitation beam into an array of focal points covering the target uniformly with very low signal fluctuation, but enlarge the power threshold for higher signal intensity. We conducted a proof-of-principle experiment on chip for the detection of bacteria with immuno-magnetic tags and immuno-SERS tags. Together with magnetic and ultrasonic operations, the target bacteria in the flow were evenly congregated on the focal plane of BTMA. It demonstrated a limit of detection of 5 cells/mL, excellent signal reproducibility (error∼4.84%), and excellent position tolerance of 500 µm in X-Y plane (error∼5.375%). It can be seen that BTMA-SERS microfluidic chip can effectively solve the contradiction between sensitivity and stability in SERS detection.


Asunto(s)
Técnicas Biosensibles , Dispositivos Laboratorio en un Chip , Microesferas , Espectrometría Raman , Espectrometría Raman/instrumentación , Espectrometría Raman/métodos , Técnicas Biosensibles/instrumentación , Límite de Detección , Diseño de Equipo , Titanio/química , Lentes , Escherichia coli/aislamiento & purificación
12.
Ecotoxicol Environ Saf ; 281: 116601, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38896905

RESUMEN

In this study, a novel sulfur/zinc co-doped biochar (SZ-BC) stabilizer was successfully developed for the remediation of mercury-contaminated soil. Results from SEM, TEM, FTIR and XRD revealed that biochar (BC) was successfully modified by sulfur and zinc. In the batch adsorption experiments, the sulfur-zinc co-pyrolysis biochar displayed excellent Hg(II) adsorption performance, with the maximum adsorption capacity of SZ-BC (261.074 mg/g) being approximately 16.5 times that of BC (15.855 mg/g). Laboratory-scale static incubation, column leaching, and plant pot experiments were conducted using biochar-based materials. At an additional dosage of 5 % mass ratio, the SZ-BC exhibits the most effective stabilization of mercury in soil, leading to a significant reduction in leaching loss compared to the control group (CK) by 51.30 %. Following 4 weeks of incubation and 2 weeks of leaching with SZ-BC, the residual mercury in the soil increased by 27.84 %. As a result, potential ecological risk index of mercury decreased by 92 % compared to the CK group. In the pot experiment, SZ-BC significantly enhanced the growth of Chinese cabbage, with biomass and root dry weight reaching 3.20 and 2.80 times that of the CK group, respectively. Additionally, the Translocation Factor (TF) and Bioconcentration Factor (BF) were reduced by 44.86 % and 74.43 %, respectively, in the SZ-BC group compared to the CK group. Moreover, SZ-BC can effectively improve enzyme activities and increase microbial communities in mercury-contaminated soils. The mechanisms of adsorption and stabilization were elucidated through electrostatic adsorption, ion exchange, surface complexation, and precipitation. These findings provide a potentially effective material for stabilizing soils contaminated with mercury.


Asunto(s)
Carbón Orgánico , Restauración y Remediación Ambiental , Mercurio , Contaminantes del Suelo , Azufre , Zinc , Carbón Orgánico/química , Mercurio/química , Contaminantes del Suelo/química , Zinc/química , Restauración y Remediación Ambiental/métodos , Adsorción , Azufre/química , Suelo/química , Brassica/química , Biodegradación Ambiental
13.
Int J Biol Macromol ; 274(Pt 1): 133342, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38908641

RESUMEN

This study explored the application of swelling pretreatment as a solution to the high cost and contamination associated with the process of 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation for nanocellulose preparation. The results demonstrated that swelling significantly expanded the fibers while preserving the degree of polymerization (DP) of cellulose (approximately 95 %). The native crystal structure and hydrogen bonding of cellulose were disrupted after swelling, leading to a reduction in crystallinity and crystallite size, and the decrease of bonding energy and content of intermolecular O6-H⋯O3'. The TEMPO-mediated oxidation processes of cellulose fibers with or without swelling were successfully fitted using a consecutive first-order reaction kinetic model. The fitting results indicated that swelling significantly reduced the activation energy of TEMPO-mediated oxidation and enhanced the reaction rate. Among three swelling systems, the NaOH/thiourea/water system exhibited the optimal promotion effect. Consequently, the swelling treatment enables a significant reduction of 30 % in the catalyst dose for the TEMPO-mediated oxidation while preserving a competitive reaction rate, yield, and product performance. Lower catalyst dosage helps to reduce cost and environmental impact, facilitating the industrial application of the TEMPO-mediated oxidation process.


Asunto(s)
Celulosa , Óxidos N-Cíclicos , Oxidación-Reducción , Celulosa/química , Óxidos N-Cíclicos/química , Cinética , Catálisis , Agua/química , Polimerizacion , Enlace de Hidrógeno , Nanoestructuras/química , Tiourea/química
14.
BMC Cancer ; 24(1): 572, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720306

RESUMEN

BACKGROUND: Postoperative central diabetes insipidus (CDI) is commonly observed in craniopharyngioma (CP) patients, and the inflammatory response plays an important role in CPs. We aimed to evaluate the predictive value of preoperative peripheral inflammatory markers and their combinations regarding CDI occurrence in CPs. METHODS: The clinical data including preoperative peripheral inflammatory markers of 208 CP patients who underwent surgical treatment were retrospectively collected and analyzed. The preoperative peripheral white blood cells (WBC), neutrophils, lymphocytes, monocytes, platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), monocyte-to-lymphocyte ratio (MLR) and PLT-to-lymphocyte ratio (PLR) were assessed in total 208 CP patients and different age and surgical approach CP patient subgroups. Their predictive values were evaluated by the receiver operator characteristic curve analysis. RESULTS: Preoperative peripheral WBC, neutrophils, NLR, dNLR, MLR, and PLR were positively correlated and lymphocyte was negatively associated with postoperative CDI occurrence in CP patients, especially when WBC ≥ 6.66 × 109/L or lymphocyte ≤ 1.86 × 109/L. Meanwhile, multiple logistic regression analysis showed that WBC > 6.39 × 109/L in the > 18 yrs age patients, WBC > 6.88 × 109/L or lymphocytes ≤ 1.85 × 109/L in the transcranial approach patients were closely associated with the elevated incidence of postoperative CDI. Furthermore, the area under the curve obtained from the receiver operator characteristic curve analysis showed that the best predictors of inflammatory markers were the NLR in total CP patients, the MLR in the ≤ 18 yrs age group and the transsphenoidal group, the NLR in the > 18 yrs age group and the dNLR in the transcranial group. Notably, the combination index NLR + dNLR demonstrated the most valuable predictor in all groups. CONCLUSIONS: Preoperative peripheral inflammatory markers, especially WBC, lymphocytes and NLR + dNLR, are promising predictors of postoperative CDI in CPs.


Asunto(s)
Craneofaringioma , Diabetes Insípida Neurogénica , Neoplasias Hipofisarias , Complicaciones Posoperatorias , Humanos , Craneofaringioma/cirugía , Craneofaringioma/sangre , Craneofaringioma/complicaciones , Femenino , Masculino , Estudios Retrospectivos , Adulto , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/sangre , Neoplasias Hipofisarias/complicaciones , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico , Adolescente , Persona de Mediana Edad , Niño , Adulto Joven , Diabetes Insípida Neurogénica/sangre , Diabetes Insípida Neurogénica/etiología , Neutrófilos , Biomarcadores/sangre , Linfocitos , Inflamación/sangre , Recuento de Leucocitos , Periodo Preoperatorio , Preescolar , Pronóstico , Curva ROC
15.
Ann Intern Med ; 177(6): 719-728, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38801778

RESUMEN

BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.


Asunto(s)
Circuncisión Masculina , Infecciones por VIH , Homosexualidad Masculina , Humanos , Masculino , Adulto , Infecciones por VIH/prevención & control , Infecciones por VIH/epidemiología , Adulto Joven , Adolescente , Persona de Mediana Edad , China/epidemiología , Incidencia , Conducta Sexual , Análisis de Intención de Tratar
16.
Cell Death Dis ; 15(5): 335, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38744853

RESUMEN

PTENα/ß, two variants of PTEN, play a key role in promoting tumor growth by interacting with WDR5 through their N-terminal extensions (NTEs). This interaction facilitates the recruitment of the SET1/MLL methyltransferase complex, resulting in histone H3K4 trimethylation and upregulation of oncogenes such as NOTCH3, which in turn promotes tumor growth. However, the molecular mechanism underlying this interaction has remained elusive. In this study, we determined the first crystal structure of PTENα-NTE in complex with WDR5, which reveals that PTENα utilizes a unique binding motif of a sequence SSSRRSS found in the NTE domain of PTENα/ß to specifically bind to the WIN site of WDR5. Disruption of this interaction significantly impedes cell proliferation and tumor growth, highlighting the potential of the WIN site inhibitors of WDR5 as a way of therapeutic intervention of the PTENα/ß associated cancers. These findings not only shed light on the important role of the PTENα/ß-WDR5 interaction in carcinogenesis, but also present a promising avenue for developing cancer treatments that target this pathway.


Asunto(s)
Péptidos y Proteínas de Señalización Intracelular , Fosfohidrolasa PTEN , Animales , Humanos , Ratones , Secuencias de Aminoácidos , Línea Celular Tumoral , Proliferación Celular/genética , Progresión de la Enfermedad , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/química , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/química , Ratones Desnudos , Neoplasias/genética , Neoplasias/patología , Neoplasias/metabolismo , Unión Proteica , Dominios Proteicos , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/química
17.
Aging (Albany NY) ; 16(10): 8772-8809, 2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38771130

RESUMEN

Immunotherapy has been a remarkable clinical advancement in cancer treatment, but only a few patients benefit from it. Metabolic reprogramming is tightly associated with immunotherapy efficacy and clinical outcomes. However, comprehensively analyzing their relationship is still lacking in lung adenocarcinoma (LUAD). Herein, we evaluated 84 metabolic pathways in TCGA-LUAD by ssGSEA. A matrix of metabolic pathway pairs was generated and a metabolic pathway-pair score (MPPS) model was established by univariable, LASSO, multivariable Cox regression analyses. The differences of metabolic reprogramming, tumor microenvironment (TME), tumor mutation burden and drug sensitivity in different MPPS groups were further explored. WGCNA and 117 machine learning algorithms were performed to identify MPPS-related genes. Single-cell RNA sequencing and in vitro experiments were used to explore the role of C1QTNF6 on TME. The results showed MPPS model accurately predicted prognosis and immunotherapy efficacy of LUAD patients regardless of sequencing platforms. High-MPPS group had worse prognosis, immunotherapy efficacy and lower immune cells infiltration, immune-related genes expression and cancer-immunity cycle scores than low-MPPS group. Seven MPPS-related genes were identified, of which C1QTNF6 was mainly expressed in fibroblasts. High C1QTNF6 expression in fibroblasts was associated with more infiltration of M2 macrophage, Treg cells and less infiltration of NK cells, memory CD8+ T cells. In vitro experiments validated silencing C1QTNF6 in fibroblasts could inhibit M2 macrophage polarization and migration. The study depicted the metabolic landscape of LUAD and constructed a MPPS model to accurately predict prognosis and immunotherapy efficacy. C1QTNF6 was a promising target to regulate M2 macrophage polarization and migration.


Asunto(s)
Adenocarcinoma del Pulmón , Inmunoterapia , Neoplasias Pulmonares , Análisis de la Célula Individual , Microambiente Tumoral , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/terapia , Adenocarcinoma del Pulmón/metabolismo , Inmunoterapia/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/metabolismo , Pronóstico , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Análisis de Secuencia de ARN , Regulación Neoplásica de la Expresión Génica , Redes y Vías Metabólicas/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo
18.
J Imaging ; 10(5)2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38786568

RESUMEN

Aphid infestations are one of the primary causes of extensive damage to wheat and sorghum fields and are one of the most common vectors for plant viruses, resulting in significant agricultural yield losses. To address this problem, farmers often employ the inefficient use of harmful chemical pesticides that have negative health and environmental impacts. As a result, a large amount of pesticide is wasted on areas without significant pest infestation. This brings to attention the urgent need for an intelligent autonomous system that can locate and spray sufficiently large infestations selectively within the complex crop canopies. We have developed a large multi-scale dataset for aphid cluster detection and segmentation, collected from actual sorghum fields and meticulously annotated to include clusters of aphids. Our dataset comprises a total of 54,742 image patches, showcasing a variety of viewpoints, diverse lighting conditions, and multiple scales, highlighting its effectiveness for real-world applications. In this study, we trained and evaluated four real-time semantic segmentation models and three object detection models specifically for aphid cluster segmentation and detection. Considering the balance between accuracy and efficiency, Fast-SCNN delivered the most effective segmentation results, achieving 80.46% mean precision, 81.21% mean recall, and 91.66 frames per second (FPS). For object detection, RT-DETR exhibited the best overall performance with a 61.63% mean average precision (mAP), 92.6% mean recall, and 72.55 on an NVIDIA V100 GPU. Our experiments further indicate that aphid cluster segmentation is more suitable for assessing aphid infestations than using detection models.

19.
Oncogene ; 43(23): 1796-1810, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38654107

RESUMEN

Lung adenocarcinoma is a malignant tumor with high morbidity and mortality. ZBTB16 plays a double role in various tumors; however, the potential mechanism of ZBTB16 in the pathophysiology of lung adenocarcinoma has yet to be elucidated. We herein observed a decreased expression of ZBTB16 mRNA and protein in lung adenocarcinoma and a significantly increased DNA methylation level of ZBTB16 in patients with lung adenocarcinoma. Analysis of public databases and patients' clinical data indicated a close association between ZBTB16 and patient survival. Ectopic expression of ZBTB16 in lung adenocarcinoma cells significantly inhibited cell proliferation, invasion, and migration. It also induced cell cycle arrest in the S phase. Meanwhile, mitotic catastrophe was induced, and DNA damage and apoptosis occurred. In line with these findings, the overexpression of ZBTB16 in xenograft mice resulted in the inhibition of tumor growth. Comprehensive analysis showed that WDHD1 was a potential target for ZBTB16. The overexpression of both isoforms of WDHD1 significantly reversed the ZBTB16-mediated inhibition of lung adenocarcinoma proliferation and cell cycle. These studies suggest that ZBTB16 impedes the progression of lung adenocarcinoma by interfering with WDHD1 transcription, making it a potential novel therapeutic target in the management of lung adenocarcinoma.


Asunto(s)
Adenocarcinoma del Pulmón , Puntos de Control del Ciclo Celular , Proliferación Celular , Replicación del ADN , Neoplasias Pulmonares , Animales , Femenino , Humanos , Masculino , Ratones , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Apoptosis/genética , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Metilación de ADN , Replicación del ADN/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Ratones Desnudos , Proteína de la Leucemia Promielocítica con Dedos de Zinc/genética , Proteína de la Leucemia Promielocítica con Dedos de Zinc/metabolismo , Transcripción Genética/genética
20.
J Proteome Res ; 23(5): 1571-1582, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38594959

RESUMEN

Reproducibility is a "proteomic dream" yet to be fully realized. A typical data analysis workflow utilizing extracted ion chromatograms (XICs) often treats the information path from identification to quantification as a one-way street. Here, we propose an XIC-centric approach in which the data flow is bidirectional: identifications are used to derive XICs whose information is in turn applied to validate the identifications. In this study, we employed liquid chromatography-mass spectrometry data from glycoprotein and human hair samples to illustrate the XIC-centric concept. At the core of this approach was XIC-based monoisotope repicking. Taking advantage of the intensity information for all detected isotopes across the whole range of an XIC peak significantly improved the accuracy and uncovered misidentifications originating from monoisotope assignment mistakes. It could also rescue non-top-ranked glycopeptide hits. Identification of glycopeptides is particularly susceptible to precursor mass errors for their low abundances, large masses, and glycans differing by 1 or 2 Da easily confused as isotopes. In addition, the XIC-centric strategy significantly reduced the problem of one XIC peak associated with multiple unique identifications, a source of quantitative irreproducibility. Taken together, the proposed approach can lead to improved identification and quantification accuracy and, ultimately, enhanced reproducibility in proteomic data analyses.


Asunto(s)
Cabello , Proteómica , Proteómica/métodos , Humanos , Cromatografía Liquida/métodos , Cabello/química , Reproducibilidad de los Resultados , Glicoproteínas/análisis , Glicoproteínas/química , Glicopéptidos/análisis , Glicopéptidos/química , Análisis de Datos , Espectrometría de Masas/métodos , Espectrometría de Masas en Tándem/métodos
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