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1.
Sci Rep ; 14(1): 9072, 2024 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-38643230

RESUMEN

To investigate the association between serum neurofilament light chain (NfL) levels, inflammatory cytokines, and cognitive function to assess their utility in the early detection of mild cognitive impairment (MCI). We conducted a cross-sectional study involving 157 community-dwelling individuals aged 55 years and above, categorized into healthy controls, MCI, and probable Alzheimer's disease (AD). Serum levels of NfL, inflammatory cytokines, and AD pathology markers were measured using enzyme-linked immunosorbent assay (ELISA). Correlations between these biomarkers and cognitive function were analyzed, and the diagnostic performance of the cognitive assessment scales and serum biomarker concentrations was evaluated using receiver operating characteristic (ROC) curve analysis. Serum NfL levels were significantly elevated in MCI and probable AD groups compared to healthy controls. Positive correlations were found between serum NfL and inflammatory cytokines IL-1ß, IL-6, and Aß40. Combining serum NfL with p-tau217 and the Boston Naming Test significantly enhanced the predictive accuracy for MCI. However, combining serum NfL with inflammatory markers did not improve MCI prediction accuracy. Elevated serum NfL is associated with cognitive impairment and inflammatory markers, suggesting its potential as a peripheral serum biomarker for MCI detection. The combination of serum NfL with p-tau217 and cognitive tests could offer a more accurate prediction of MCI, providing new insights for AD treatment strategies.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Estudios Transversales , Filamentos Intermedios , Proteínas de Neurofilamentos , Disfunción Cognitiva/diagnóstico , Biomarcadores , Proteínas tau , Péptidos beta-Amiloides
2.
Phys Rev Lett ; 132(15): 156301, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38683008

RESUMEN

A valley filter capable of generating a valley-polarized current is a crucial element in valleytronics, yet its implementation remains challenging. Here, we propose a valley filter made of a graphene bilayer which exhibits a 1D moiré pattern in the overlapping region of the two layers controlled by heterostrain. In the presence of a lattice modulation between layers, electrons propagating in one layer can have valley-dependent dissipation due to valley asymmetric interlayer coupling, thus giving rise to a valley-polarized current. Such a process can be described by an effective non-Hermitian theory, in which the valley filter is driven by a valley-resolved non-Hermitian skin effect. Nearly 100% valley polarization can be achieved within a wide parameter range and the functionality of the valley filter is electrically tunable. The non-Hermitian topological scenario of the valley filter ensures high tolerance against imperfections such as disorder and edge defects. Our work opens a new route for efficient and robust valley filters while significantly relaxing the stringent implementation requirements.

3.
Foods ; 13(8)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38672838

RESUMEN

Seasonal (temporal) variations can influence the δ13C, δ2H, δ18O, and δ15N values and nutrient composition of organic (ORG), green (GRE), and conventional (CON) vegetables with a short growth cycle. Stable isotope ratio mass spectrometry (IRMS) and near-infrared spectroscopy (NIRS) combined with the partial least squares-discriminant analysis (PLS-DA) method were used to investigate seasonal effects on the identification of ORG, GRE, and CON Brassica chinensis L. samples (BCs). The results showed that δ15N values had significant differences among the three cultivation methods and that δ13C, δ2H, and δ18O values were significantly higher in winter and spring and lower in summer. The NIR spectra were relatively clustered across seasons. Neither IRMS-PLS-DA nor NIRS-PLS-DA could effectively identify all BC cultivation methods due to seasonal effects, while IRMS-NIRS-PLS-DA combined with Norris smoothing and derivative pretreatment had better predictive abilities, with an 89.80% accuracy for ORG and BCs, 88.89% for ORG and GRE BCs, and 75.00% for GRE and CON BCs. The IRMS-NIRS-PLS-DA provided an effective and robust method to identify BC cultivation methods, integrating multi-seasonal differences.

4.
iScience ; 27(4): 109447, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38523790

RESUMEN

Maternal hyperhomocysteinemia is widely considered as an independent risk of congenital heart disease (CHD). However, whether high paternal homocysteine causes CHD remains unknown. Here, we showed that increased homocysteine levels of male mice caused decreased sperm count, sperm motility defect and ventricular septal defect of the offspring. Moreover, high levels of paternal homocysteine decrease sperm DNMT3A/3B, accompanied with changes in DNA methylation levels in the promoter regions of CHD-related genes. Folic acid supplement could decrease the occurrence of VSD in high homocysteine male mice. This study reveals that increased paternal homocysteine level increases VSD risk in the offspring, indicating that decreasing paternal homocysteine may be an intervening target of CHD.

5.
Environ Sci Pollut Res Int ; 31(17): 25046-25058, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38466387

RESUMEN

Regarding the impact of microplastics (MPs) on the male reproductive system, previous studies have identified a variety of MPs in both human semen and testicular samples. These studies have put forward the hypothesis that small particles can enter the semen through the epididymis and seminal vesicles. Here, we performed qualitative and quantitative analyses of MPs in human testis, semen, and epididymis samples, as well as in testis, epididymis, seminal vesicle, and prostate samples from mice via pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). The goal of this approach was to comprehensively characterize the distribution of MPs within the male reproductive system. Additionally, we aimed to evaluate potential sources of MPs identified in semen, as well as to identify possible sources of overall MP exposure. Our results highlighted a general atlas of MPs in the male reproductive system and suggested that MPs in semen may originate from the epididymis, seminal vesicles, and prostate. An exposure questionnaire, coupled with the characteristics of the MPs detected in the male reproductive system, revealed that high urbanization, home-cooked meals, and using scrub cleansers were important sources of MP exposure in men. These findings may provide novel insights into alleviating the exposure of men to MPs.


Asunto(s)
Microplásticos , Testículo , Humanos , Masculino , Ratones , Animales , Plásticos , Genitales Masculinos , Vesículas Seminales , Semen
6.
Biomater Sci ; 12(9): 2321-2330, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38488841

RESUMEN

Nanotherapies, valued for their high efficacy and low toxicity, frequently serve as antitumor treatments, but do not readily penetrate deep into tumor tissues and cells. Here we developed an improved tumor-penetrating peptide (TPP)-based drug delivery system. Briefly, the established TPP iNGR was modified to generate a linear NGR peptide capable of transporting nanotherapeutic drugs into tumors through a CendR pathway-dependent, neuropilin-1 receptor-mediated process. Although TPPs have been reported to reach intended tumor targets, they often fail to penetrate cell membranes to deliver tumoricidal drugs to intracellular targets. We addressed this issue by harnessing cell penetrating peptide technology to develop a liposome-based multibarrier-penetrating delivery system (mbPDS) with improved synergistic drug penetration into deep tumor tissues and cells. The system incorporated doxorubicin-loaded liposomes coated with nona-arginine (R9) CPP and cyclic iNGR (CRNGRGPDC) molecules, yielding Lip-mbPDS. Lip-mbPDS tumor-targeting, tumor cell/tissue-penetrating and antitumor capabilities were assessed using CD13-positive human fibrosarcoma-derived cell (HT1080)-based in vitro and in vivo tumor models. Lip-mbPDS evaluation included three-dimensional layer-by-layer confocal laser scanning microscopy, cell internalization/toxicity assays, three-dimensional tumor spheroid-based penetration assays and antitumor efficacy assays conducted in an animal model. Lip-mbPDS provided enhanced synergistic drug penetration of multiple biointerfaces for potentially deep tumor therapeutic outcomes.


Asunto(s)
Péptidos de Penetración Celular , Doxorrubicina , Sistemas de Liberación de Medicamentos , Liposomas , Humanos , Animales , Doxorrubicina/química , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Péptidos de Penetración Celular/química , Línea Celular Tumoral , Liposomas/química , Ratones , Portadores de Fármacos/química , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacología , Ratones Desnudos , Péptidos Cíclicos/química , Péptidos Cíclicos/administración & dosificación
7.
Artículo en Inglés | MEDLINE | ID: mdl-38430325

RESUMEN

PURPOSE: To identify the genetic cause of a cryptorchidism patient carrying a non-canonical splicing variant highlighted by SPCards platform in RXFP2 and to provide a comprehensive overview of RXFP2 variants with cryptorchidism correlation. METHODS: We identified a homozygous non-canonical splicing variant by whole-exome sequencing and Sanger sequencing in a case with cryptorchidism and non-obstructive azoospermia (NOA). As the pathogenicity of this non-canonical splicing variant remained unclear, we initially utilized the SPCards platform to predict its pathogenicity. Subsequently, we employed a minigene splicing assay to further evaluate the influence of the identified splicing variant. Microdissection testicular sperm extraction (micro-TESE) combined with intracytoplasmic sperm injection (ICSI) was performed. PubMed and Human Genome Variant Database (HGMD) were queried to search for RXFP2 variants. RESULTS: We identified a homozygous non-canonical splicing variant (NM_130806: c.1376-12A > G) in RXFP2, and confirmed this variant caused aberrant splicing of exons 15 and 16 of the RXFP2 gene: 11 bases were added in front of exon 16, leading to an abnormal transcript initiation and a frameshift. Fortunately, the patient successfully obtained his biological offspring through micro-TESE combined with ICSI. Four cryptorchidism-associated variants in RXFP2 from 90 patients with cryptorchidism were identified through a literature search in PubMed and HGMD, with different inheritance patterns. CONCLUSION: This is the first cryptorchidism case carrying a novel causative non-canonical splicing RXFP2 variant. The combined approach of micro-TESE and ICSI contributed to an optimal pregnancy outcome. Our literature review demonstrated that RXFP2 variants caused cryptorchidism in a recessive inheritance pattern, rather than a dominant pattern.

8.
J Med Genet ; 2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38341271

RESUMEN

BACKGROUND: The association between the TDRD6 variants and human infertility remains unclear, as only one homozygous missense variant of TDRD6 was found to be associated with oligoasthenoteratozoospermia (OAT). METHODS: Whole-exome sequencing and Sanger sequencing were employed to identify potential pathogenic variants of TDRD6 in infertile men. Histology, immunofluorescence, immunoblotting and ultrastructural analyses were conducted to clarify the structural and functional abnormalities of sperm in mutated patients. Tdrd6-knockout mice were generated using the CRISPR-Cas9 system. Total RNA-seq and single-cell RNA-seq (scRNA-seq) analyses were used to elucidate the underlying molecular mechanisms, followed by validation through quantitative RT-PCR and immunostaining. Intracytoplasmic sperm injection (ICSI) was also used to assess the efficacy of clinical treatment. RESULTS: Bi-allelic TDRD6 variants were identified in five unrelated Chinese individuals with OAT, including homozygous loss-of-function variants in two consanguineous families. Notably, besides reduced concentrations and impaired motility, a significant occurrence of acrosomal hypoplasia was detected in multiple spermatozoa among five patients. Using the Tdrd6-deficient mice, we further elucidate the pivotal role of TDRD6 in spermiogenesis and acrosome identified. In addition, the mislocalisation of crucial chromatoid body components DDX4 (MVH) and UPF1 was also observed in round spermatids from patients harbouring TDRD6 variants. ScRNA-seq analysis of germ cells from a patient with TDRD6 variants revealed that TDRD6 regulates mRNA metabolism processes involved in spermatid differentiation and cytoplasmic translation. CONCLUSION: Our findings strongly suggest that TDRD6 plays a conserved role in spermiogenesis and confirms the causal relationship between TDRD6 variants and human OAT. Additionally, this study highlights the unfavourable ICSI outcomes in individuals with bi-allelic TDRD6 variants, providing insights for potential clinical treatment strategies.

9.
Int J Biol Macromol ; 261(Pt 2): 129885, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38309385

RESUMEN

The relationships between the physicochemical properties of wheat starch and the characteristics of 3D printing were studied by extracting wheat starch from three kinds of wheat flour with different gluten contents. The results showed that wheat starch extracted from high-gluten wheat flour (MS) and medium-gluten wheat flour (ZS) exhibited more accurate printing and better quality than wheat starch extracted from low-gluten wheat flour (JS). ZS had moderate final viscosity and setback value, indicating good extrusion performance and high elasticity. Therefore, the printing quality of ZS was the best, with obvious and unbroken printing lines. The 3D-printed sample made from ZS had dimensions closest to the designed CAD model. Additionally, there were no significant differences in the functional groups of native starch, gelatinized starch, and post-3D-printed starch among the three types. ZS exhibited the most regular microstructure. Therefore, wheat starch extracted from medium-gluten wheat flour was determined to be the most suitable for 3D printing. This research could provide a new theoretical basis for the application of wheat starch in 3D-printed food and offer new technical support for practical production.


Asunto(s)
Almidón , Triticum , Almidón/química , Triticum/química , Harina , Glútenes/química , Geles
10.
Appl Neuropsychol Adult ; : 1-10, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38316014

RESUMEN

OBJECTIVE: This study aims to evaluate and analyze the standard diagnostic methods for mild cognitive impairment (MCI). METHODS: This study used a prospective case-control study to examine baseline data and diagnostic indicators in a population of elderly with MCI. Based on different cognitive abilities, this study divided MCI and healthy control groups. The diagnostic indicators included CDT, MOCA, MMSE, PSQI, MBI, DST, HAMD, AD-related blood markers, and olfactory testing. The diagnostic value of each indicator was done using the ROC curve. RESULTS: This study included 240 adult participants, 135 in the health group and 105 in the MCI group. A comparison of baseline data revealed statistically significant differences between the two groups regarding age, blood glucose, MMSE, CTD, MOCA, ability to perform daily living, AD-related blood indices and olfactory tests (all p < 0.05). Logistic regression analysis statistically showed that age, MOCA, and CDT were independent diagnostic factors for MCI (all p < 0.05). Combining these three indicators has the best diagnostic specificity (92.54%). AD-related blood and olfactory tests indices had only moderate diagnostic values (AUC: 0.7-0.8). CONCLUSION: Age, MOCA, and CDT are good indicators for diagnosing early-stage MCI. AD-related blood indices and olfactory tests can serve as valuable adjuncts in diagnosing MCI.

11.
Nat Commun ; 15(1): 1353, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38355624

RESUMEN

There is strong evidence that obesity is a risk factor for poor semen quality. However, the effects of multigenerational paternal obesity on the susceptibility to cadmium (a reproductive toxicant)-induced spermatogenesis disorders in offspring remain unknown. Here, we show that, in mice, spermatogenesis and retinoic acid levels become progressively lower as the number of generations exposed to a high-fat diet increase. Furthermore, exposing several generations of mice to a high fat diet results in a decrease in the expression of Wt1, a transcription factor upstream of the enzymes that synthesize retinoic acid. These effects can be rescued by injecting adeno-associated virus 9-Wt1 into the mouse testes of the offspring. Additionally, multigenerational paternal high-fat diet progressively increases METTL3 and Wt1 N6-methyladenosine levels in the testes of offspring mice. Mechanistically, treating the fathers with STM2457, a METTL3 inhibitor, restores obesity-reduced sperm count, and decreases Wt1 N6-methyladenosine level in the mouse testes of the offspring. A case-controlled study shows that human donors who are overweight or obese exhibit elevated N6-methyladenosine levels in sperm and decreased sperm concentration. Collectively, these results indicate that multigenerational paternal obesity enhances the susceptibility of the offspring to spermatogenesis disorders by increasing METTL3-mediated Wt1 N6-methyladenosine modification.


Asunto(s)
Infertilidad Masculina , Análisis de Semen , Animales , Humanos , Masculino , Ratones , Dieta Alta en Grasa/efectos adversos , Padre , Infertilidad Masculina/genética , Metiltransferasas , Obesidad/metabolismo , Semen/metabolismo , Tretinoina
12.
Prev Med ; 179: 107844, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38176446

RESUMEN

OBJECTIVE: A variety of unhealthy sleep behaviors have been shown to be associated with an increased risk of urologic cancers. However, little is known about the association between the overall sleep patterns and urologic cancers. To prospectively investigate the associations between a healthy sleep pattern and the risks of urologic cancers, including bladder cancer (BCa) and renal cell carcinoma (RCC). METHODS: In this prospective cohort study, 377,144 participants free of cancer at baseline were recruited from the UK Biobank. Data on sleep behaviors were collected through questionnaires at recruitment. The incident urologic cancer cases were determined through linkage to national cancer and death registries. We established a healthy sleep score according to five sleep traits (sleep duration, chronotype, insomnia, snoring, and daytime sleepiness). Cox proportional hazard regression models were used to calculate the adjusted hazard ratios and 95% confidence intervals to assess the relationship between the healthy sleep score and the risk of urologic cancers. RESULTS: During a median of ≥9 years of follow-up, we identified 1986 incident urologic cancer cases, including 1272 BCa cases and 706 RCC cases. Compared with the participants with a poor sleep pattern (score of 0-2), the multivariable-adjusted hazard ratio and 95% confidence interval were 0.85 (0.75 to 0.96) for urologic cancers, 0.80 (0.68 to 0.93) for BCa, and 0.91 (0.74, 1.12) for RCC, respectively, for those with the healthier sleep pattern (score of 4-5). CONCLUSION: Our results indicate that a healthy sleep pattern is associated with lower risks of urologic cancers.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Estudios Prospectivos , Carcinoma de Células Renales/complicaciones , Sueño , Ronquido/complicaciones , Neoplasias Renales/epidemiología , Neoplasias Renales/complicaciones , Factores de Riesgo
13.
Phytochemistry ; 219: 113986, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38219853

RESUMEN

The plant Andrographis paniculata has a long history of cultivation in Southeast Asia, especially its extensive anti-inflammatory activity, and the famous natural antibiotic andrographolide comes from this plant. In China, A. paniculata, as the main crop, has become a major source of traditional Chinese medicine (TCM) for the clinical treatment of inflammation. To further explore the diverse diterpene lactones with better anti-inflammatory activity from A. paniculata, twenty-one ent-labdanes, including six undescribed compounds (andropanilides D-I), were isolated. Their structures with absolute configurations were thoroughly determined by comprehensive NMR spectroscopic data, HRESIMS analysis and quantum chemical calculations. All isolated compounds were evaluated for anti-inflammatory activities based on the Griess method. Meanwhile, after structure-activity relationships analysis, the anti-inflammatory activity of andropanilide D (1) (IC50 = 2.31 µM) was found to be better than that of the positive control drug (dexamethasone, IC50 = 6.52 µM) and andrographolide (IC50 = 5.89 µM). Further mechanisms of activity indicated that andropanilide D significantly reduced the secretion of TNF-α, IL-6 and IL-1ß and downregulated the protein expression of COX-2 and iNOS in LPS-induced RAW264.7 macrophages in a concentration-dependent manner based on Western blot and ELISA experiments. In conclusion, andropanilide D possesses potential medicinal value for the treatment of inflammation and further expands the material basis of the anti-inflammatory effect of A. paniculata.


Asunto(s)
Andrographis , Diterpenos , Andrographis paniculata , Andrographis/química , Andrographis/metabolismo , Antiinflamatorios/farmacología , Extractos Vegetales/farmacología , Diterpenos/química , Inflamación
14.
Clin Genet ; 105(1): 99-105, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37715646

RESUMEN

Non-obstructive azoospermia (NOA) is the most severe form of human male infertility, and the genetic causes of NOA with meiotic arrest remain largely unclear. In this study, we identified novel compound heterozygous MEIOB variants (c.814C > T: p.R272X and c.976G > A: p.A326T) and a previously undescribed homozygous non-canonical splicing variant of MEIOB (c.528 + 3A > C) in two NOA-affected individuals from two irrelevant Chinese families. MEIOB missense variant (p.A326T) significantly reduced protein abundance and nonsense variant (p.R272X) produced a truncated protein. Both of two variants impaired the MEIOB-SPATA22 interaction. The MEIOB non-canonical splicing variant resulted in whole Exon 6 skipping by minigene assay, which was predicted to produce a frameshift truncated protein (p.S111Rfs*32). Histological and immunostaining analysis indicated that both patients exhibited a similar phenotype as we previously reported in Meiob mutant mice, that is, absence of spermatids in seminiferous tubules and meiotic arrest. Our study identified three novel pathogenic variants of MEIOB in NOA patients, extending the mutation spectrum of the MEIOB and highlighting the contribution of meiotic recombination related genes in human fertility.


Asunto(s)
Azoospermia , Infertilidad Masculina , Humanos , Masculino , Ratones , Animales , Azoospermia/genética , Azoospermia/patología , Infertilidad Masculina/genética , Mutación/genética , Proteínas/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Meiosis/genética , Proteínas de Unión al ADN/genética
15.
Eur J Pharm Sci ; 193: 106671, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38104907

RESUMEN

PURPOSE: A novel 18F-radiolabeled somatostatin analogue, [Al18F]NODA-MPAA-HTA, was synthesized and evaluated for positron emission tomography (PET) imaging of Neuroendocrine tumors (NETs). [Al18F]NODA-MPAA-HTA was designed and synthesized by conjugating 18F nuclide with a modified KE108 peptide, a somatostatin analog with high affinity for all five subtypes of somatostatin receptors (SSTR 1-5), through coupling a bifunctional chelator (NODA) to target somatostatin receptor (SSTR) positive tumors. METHODS: The amino group of KE108 peptide, a SSTRs-targeting pharmacophore, was conjugated with the carboxyl group of NODA by a condensation reaction to obtain the labeling precursor of [Al18F]NODA-MPAA-HTA, in which its precursor was obtained through Fmoc solid-phase methods. A novel methodology for Al18F labeling of chelating agent-biomolecule conjugates was used to synthesize [Al18F]NODA-MPAA-HTA. In vitro stabilities of [Al18F]NODA-MPAA-HTA were evaluated by incubating it in saline or bovine serum for 2 h. Ex vivo biodistribution and in vivo imaging of [Al18F]NODA-MPAA-HTA were further investigated to evaluate its SSTRs targeting ability and feasibility for the diagnosis of NETs using PET imaging. RESULTS: [Al18F]NODA-MPAA-HTA was synthesized using a one-step 18F-AlF labeling procedure resulting in moderate radiochemical yield (60-80 %, non-decay corrected) and high radiochemical purity (>95 %). It exhibited good hydrophilicity and excellent stability in vitro, with a molar activity of 122 GBq/µmol. At 30 min and 60 min, the uptake of [Al18F] NODA-MPAA-HTA by HEK293-SSTR2 cells was 5.47 ± 0.97 %/105 cells and 12.11 ± 0.32 %/105 cells, respectively. The affinity of [Al18F]NODA-MPAA-HTA for SSTR2 was determined to be 8.77 ± 1.14 nM. In micro-PET imaging of HEK293-SSTR2 tumor-bearing mice, [Al18F]NODA-MPAA-HTA showed high tumor uptake of radioactivity and a high tumor-to-muscle ratio. Biodistribution results confirmed that radioactivity uptake in the tumor was significantly higher than that in the muscle by more than five-fold (P<0.001). Furthermore, the relatively low bone uptake of [Al18F]NODA-MPAA-HTA suggested that defluorination did not occur in vivo. These preliminary results provide experimental evidence for further study of Al18F-labeled somatostatin analogues as tumor probes for PET imaging of NETs. CONCLUSION: Fluorine-18 is widely used as a radionuclide for the production of radiopharmaceuticals for positron emission tomography (PET). Due to its short half-life (T1/2,109.8 min), its ease of production will facilitate the widespread dissemination of this radiopharmaceutical. A high-quality [Al18F]NODA-MPAA-HTA was synthesized with satisfactory yield. This radiopharmaceutical demonstrated higher tumor uptake and better tumor-to-muscle contrast, resulting to excellent image quality. These findings suggest that the novel 18F-labeled somatostatin analogue, [Al18F]NODA-MPAA-HTA, is a promising tool for PET imaging of NETs.


Asunto(s)
Tumores Neuroendocrinos , Somatostatina , Humanos , Ratones , Animales , Receptores de Somatostatina/metabolismo , Tumores Neuroendocrinos/diagnóstico por imagen , Radiofármacos/química , Distribución Tisular , Células HEK293 , Tomografía de Emisión de Positrones/métodos , Radioisótopos de Flúor/química , Péptidos/química , Línea Celular Tumoral
16.
bioRxiv ; 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38076825

RESUMEN

Microbes inhabit natural environments that are remarkably dynamic, with sudden environmental shifts that require immediate action by the cell. To cope with changing environments, microbes are equipped with regulated response mechanisms that are only activated when needed. However, when exposed to extreme environments such as clinical antibiotic treatments, complete loss of regulation is frequently observed. Although recent studies suggest that the initial evolution of microbes in new environments tends to favor mutations in regulatory pathways, it is not clear how this evolution is affected by how quickly conditions change (i.e. dynamics), or which mechanisms are commonly used to implement new regulation. Here, we perform experimental evolution on continuous cultures of E. coli carrying the tetracycline resistance tet operon to identify specific types of mutations that adapt drug responses to different dynamical regimens of drug administration. When cultures are evolved under gradually increasing tetracycline concentrations, we observe no mutations in the tet operon, but a predominance of fine-tuning mutations increasing the affinity of alternative efflux pump AcrB to tetracycline. When cultures are instead periodically exposed to large drug doses, all populations developed transposon insertions in repressor TetR, resulting in loss of regulation of efflux pump TetA. We use a mathematical model of the dynamics of antibiotic responses to show that sudden exposure to large drug concentrations can overwhelm regulated responses, which cannot induce resistance fast enough, resulting in fitness advantage for constitutive expression of resistance. These results help explain the loss of regulation of antibiotic resistance by opportunistic pathogens evolving in clinical environments. Our experiment supports the notion that initial evolution in new ecological niches proceeds largely through regulatory mutations and suggests that transposon insertions are a main mechanism driving this process.

17.
Nat Prod Res ; : 1-5, 2023 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-38087981

RESUMEN

Three new cadinene sesquiterpenoids 1-3, were isolated from the aerial sections of Ageratina adenophora using various chromatographic techniques. Their structures were characterised by comprehensive spectroscopic investigations (including 1D, 2D-NMR and HRMS), and single crystal X-ray diffraction. The cytotoxic activity of new compounds 1-3 were evaluated by testing in vitro tumour growth inhibitory rate against five human tumour cell lines, HL-60, A-549, SMMC-7721, MDA-MB-231, and SW480.

18.
J Agric Food Chem ; 71(50): 20092-20104, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38051256

RESUMEN

Tomato cultivars with contrasting resistance to pathogens regulate root exudates differentially in response to Ralstonia solanacearum attacks. However, strategies using innate root exudates against infection remain unknown. This study analyzed the innate root exudates of two tomato cultivars and their functions in regulating R. solanacearum infection. The innate root exudates differed between the two cultivars. Astaxanthin released from resistant plants inhibited colonization by R. solanacearum but promoted motility, while neferine released from susceptible plants suppressed motility and colonization. The secretion of astaxanthin in resistant tomatoes promoted the growth of biocontrol fungi in soil and reduced the abundance of pathogenic fungi. Neferine secreted by the susceptible cultivar inhibited the relative abundance of the bacterial-biocontrol-related Bacillus genus, indirectly reducing the soil's immune capacity. This study revealed contrasting strategies using root exudates in resistant and susceptible tomato cultivars to cope with R. solanacearum infection, providing a basis for breeding disease-resistant cultivars.


Asunto(s)
Ralstonia solanacearum , Solanum lycopersicum , Habilidades de Afrontamiento , Fitomejoramiento , Suelo , Enfermedades de las Plantas/microbiología
19.
20.
Math Biosci Eng ; 20(12): 21588-21610, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-38124611

RESUMEN

Accurate cloud detection is an important step to improve the utilization rate of remote sensing (RS). However, existing cloud detection algorithms have difficulty in identifying edge clouds and broken clouds. Therefore, based on the channel data of the Himawari-8 satellite, this work proposes a method that combines the feature enhancement module with the Gaussian mixture model (GMM). First, statistical analysis using the probability density functions (PDFs) of spectral data from clouds and underlying surface pixels was conducted, selecting cluster features suitable for daytime and nighttime. Then, in this work, the Laplacian operator is introduced to enhance the spectral features of cloud edges and broken clouds. Additionally, enhanced spectral features are input into the debugged GMM model for cloud detection. Validation against visual interpretation shows promising consistency, with the proposed algorithm outperforming other methods such as RF, KNN and GMM in accuracy metrics, demonstrating its potential for high-precision cloud detection in RS images.

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