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1.
Proc Natl Acad Sci U S A ; 120(45): e2304179120, 2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37903265

RESUMEN

The unexpected discovery of hot Jupiters challenged the classical theory of planet formation inspired by our solar system. Until now, the origin and evolution of hot Jupiters are still uncertain. Determining their age distribution and temporal evolution can provide more clues into the mechanism of their formation and subsequent evolution. Using a sample of 383 giant planets around Sun-like stars collected from the kinematic catalogs of the Planets Across Space and Time project, we find that hot Jupiters are preferentially hosted by relatively younger stars in the Galactic thin disk. We subsequently find that the frequency of hot Jupiters declines with age as [Formula: see text]. In contrast, the frequency of warm/cold Jupiters shows no significant dependence on age. Such a trend is expected from the tidal evolution of hot Jupiters' orbits, and our result offers supporting evidence using a large sample. We also perform a joint analysis on the planet frequencies in the stellar age-metallicity plane. The result suggests that the frequencies of hot Jupiters and warm/cold Jupiters, after removing the age dependence are both correlated with stellar metallicities as [Formula: see text] and [Formula: see text], respectively. Moreover, we show that the above correlations can explain the bulk of the discrepancy in hot Jupiter frequencies inferred from the transit and radial velocity (RV) surveys, given that RV targets tend to be more metal-rich and younger than transits.

2.
Proc Natl Acad Sci U S A ; 119(32): e2202371119, 2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35917353

RESUMEN

Epstein-Barr virus (EBV) infects more than 90% of the world's adult population and accounts for a significant cancer burden of epithelial and B cell origins. Glycoprotein B (gB) is the primary fusogen essential for EBV entry into host cells. Here, we isolated two EBV gB-specific neutralizing antibodies, 3A3 and 3A5; both effectively neutralized the dual-tropic EBV infection of B and epithelial cells. In humanized mice, both antibodies showed effective protection from EBV-induced lymphoproliferative disorders. Cryoelectron microscopy analyses identified that 3A3 and 3A5 bind to nonoverlapping sites on domains D-II and D-IV, respectively. Structure-based mutagenesis revealed that 3A3 and 3A5 inhibit membrane fusion through different mechanisms involving the interference with gB-cell interaction and gB activation. Importantly, the 3A3 and 3A5 epitopes are major targets of protective gB-specific neutralizing antibodies elicited by natural EBV infection in humans, providing potential targets for antiviral therapies and vaccines.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Proteínas Virales , Animales , Anticuerpos Neutralizantes/química , Anticuerpos Neutralizantes/aislamiento & purificación , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/química , Anticuerpos Antivirales/aislamiento & purificación , Anticuerpos Antivirales/uso terapéutico , Microscopía por Crioelectrón , Infecciones por Virus de Epstein-Barr/prevención & control , Infecciones por Virus de Epstein-Barr/terapia , Herpesvirus Humano 4/inmunología , Humanos , Fusión de Membrana , Ratones , Proteínas Virales/inmunología
3.
Proc Natl Acad Sci U S A ; 119(34): e2204256119, 2022 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-35972965

RESUMEN

Antibody therapeutics for the treatment of COVID-19 have been highly successful. However, the recent emergence of the Omicron variant has posed a challenge, as it evades detection by most existing SARS-CoV-2 neutralizing antibodies (nAbs). Here, we successfully generated a panel of SARS-CoV-2/SARS-CoV cross-neutralizing antibodies by sequential immunization of the two pseudoviruses. Of the potential candidates, we found that nAbs X01, X10, and X17 offer broad neutralizing potential against most variants of concern, with X17 further identified as a Class 5 nAb with undiminished neutralization against the Omicron variant. Cryo-electron microscopy structures of the three antibodies together in complex with each of the spike proteins of the prototypical SARS-CoV, SARS-CoV-2, and Delta and Omicron variants of SARS-CoV-2 defined three nonoverlapping conserved epitopes on the receptor-binding domain. The triple-antibody mixture exhibited enhanced resistance to viral evasion and effective protection against infection of the Beta variant in hamsters. Our findings will aid the development of antibody therapeutics and broad vaccines against SARS-CoV-2 and its emerging variants.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Epítopos , SARS-CoV-2 , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Vacunas contra la COVID-19/inmunología , Secuencia Conservada , Cricetinae , Microscopía por Crioelectrón , Epítopos/inmunología , Humanos , Ratones , Pruebas de Neutralización , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/inmunología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/genética
4.
BMC Bioinformatics ; 25(1): 35, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38254030

RESUMEN

BACKGROUND: Natural proteins occupy a small portion of the protein sequence space, whereas artificial proteins can explore a wider range of possibilities within the sequence space. However, specific requirements may not be met when generating sequences blindly. Research indicates that small proteins have notable advantages, including high stability, accurate resolution prediction, and facile specificity modification. RESULTS: This study involves the construction of a neural network model named TopoProGenerator(TPGen) using a transformer decoder. The model is trained with sequences consisting of a maximum of 65 amino acids. The training process of TopoProGenerator incorporates reinforcement learning and adversarial learning, for fine-tuning. Additionally, it encompasses a stability predictive model trained with a dataset comprising over 200,000 sequences. The results demonstrate that TopoProGenerator is capable of designing stable small protein sequences with specified topology structures. CONCLUSION: TPGen has the ability to generate protein sequences that fold into the specified topology, and the pretraining and fine-tuning methods proposed in this study can serve as a framework for designing various types of proteins.


Asunto(s)
Aminoácidos , Suministros de Energía Eléctrica , Secuencia de Aminoácidos , Lenguaje , Aprendizaje
5.
BMC Genomics ; 25(1): 222, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38418975

RESUMEN

Shepherd's crook (Geodorum) is a genus of protected orchids that are valuable both medicinally and ornamentally. Geodorum eulophioides (GE) is an endangered and narrowly distributed species, and Geodorum densiflorum (GD) and Geodorum attenuatum (GA) are widespread species. The growth of orchids depend on microorganisms. However, there are few studies on the microbial structure in Geodorum, and little is known about the roles of microorganisms in the endangered mechanism of G. eulophioides. This study analyzed the structure and composition of bacterial and fungal communities in the roots and rhizosphere soil of GE, GD, and GA. The results showed that Delftia, Bordetella and norank_f_Xanthobacteraceae were the dominant bacteria in the roots of Geodorum, while norank_f_Xanthobacteraceae, Gaiella and norank_f_norank_o_Gaiellales were the dominant bacteria in the rhizosphere soil of Geodorum. In the roots, the proportion of Mycobacterium in GD_roadside was higher than that in GD_understory, on the contrary, the proportion of Fusarium, Delftia and Bordetella in GD_roadside was lower than that in GD_understory. Compared with the GD_understory, the roots of GD_roadside had lower microbial diversity. In the endangered species GE, Russula was the primary fungus in the roots and rhizosphere soil, with fungal diversity lower than in the more widespread species. Among the widespread species, the dominant fungal genera in the roots and rhizosphere soil were Neocosmospora, Fusarium and Coprinopsis. This study enhances our understanding of microbial composition and diversity, providing fundamental information for future research on microbial contributions to plant growth and ecosystem function in Geodorum.


Asunto(s)
Agaricales , Fusarium , Rizosfera , Suelo/química , Ecosistema , Hongos/genética , Microbiología del Suelo , Raíces de Plantas/microbiología , Bacterias/genética
6.
Am J Physiol Gastrointest Liver Physiol ; 326(3): G205-G215, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38193187

RESUMEN

Single-cell RNA-sequencing (scRNA-seq) has emerged as a powerful technique to identify novel cell markers, developmental trajectories, and transcriptional changes during cell differentiation and disease onset and progression. In this review, we highlight recent scRNA-seq studies of the gastric corpus in both human and murine systems that have provided insight into gastric organogenesis, identified novel markers for the various gastric lineages during development and in adults, and revealed transcriptional changes during regeneration and tumorigenesis. Overall, by elucidating transcriptional states and fluctuations at the cellular level in healthy and disease contexts, scRNA-seq may lead to better, more personalized clinical treatments for disease progression.


Asunto(s)
Análisis de la Célula Individual , Estómago , Adulto , Humanos , Animales , Ratones , Diferenciación Celular , Análisis de la Célula Individual/métodos , Análisis de Secuencia de ARN/métodos , Perfilación de la Expresión Génica/métodos
7.
Am J Physiol Gastrointest Liver Physiol ; 326(5): G504-G524, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38349111

RESUMEN

Genotoxic agents such as doxorubicin (DXR) can cause damage to the intestines that can be ameliorated by fasting. How fasting is protective and the optimal timing of fasting and refeeding remain unclear. Here, our analysis of fasting/refeeding-induced global intestinal transcriptional changes revealed metabolic shifts and implicated the cellular energetic hub mechanistic target of rapamycin complex 1 (mTORC1) in protecting from DXR-induced DNA damage. Our analysis of specific transcripts and proteins in intestinal tissue and tissue extracts showed that fasting followed by refeeding at the time of DXR administration reduced damage and caused a spike in mTORC1 activity. However, continued fasting after DXR prevented the mTORC1 spike and damage reduction. Surprisingly, the mTORC1 inhibitor, rapamycin, did not block fasting/refeeding-induced reduction in DNA damage, suggesting that increased mTORC1 is dispensable for protection against the initial DNA damage response. In Ddit4-/- mice [DDIT4 (DNA-damage-inducible transcript 4) functions to regulate mTORC1 activity], fasting reduced DNA damage and increased intestinal crypt viability vs. ad libitum-fed Ddit4-/- mice. Fasted/refed Ddit4-/- mice maintained body weight, with increased crypt proliferation by 5 days post-DXR, whereas ad libitum-fed Ddit4-/- mice continued to lose weight and displayed limited crypt proliferation. Genes encoding epithelial stem cell and DNA repair proteins were elevated in DXR-injured, fasted vs. ad libitum Ddit4-/- intestines. Thus, fasting strongly reduced intestinal damage when normal dynamic regulation of mTORC1 was lost. Overall, the results confirm that fasting protects the intestines against DXR and suggests that fasting works by pleiotropic - including both mTORC1-dependent and independent - mechanisms across the temporally dynamic injury response.NEW & NOTEWORTHY New findings are 1) DNA damage reduction following a 24-h fast depends on the timing of postfast refeeding in relation to chemotherapy initiation; 2) fasting/refeeding-induced upregulation of mTORC1 activity is not required for early (6 h) protection against DXR-induced DNA damage; and 3) fasting increases expression of intestinal stem cell and DNA damage repair genes, even when mTORC1 is dysregulated, highlighting fasting's crucial role in regulating mTORC1-dependent and independent mechanisms in the dynamic recovery process.


Asunto(s)
Doxorrubicina , Intestino Delgado , Intestinos , Ratones , Animales , Intestinos/fisiología , Diana Mecanicista del Complejo 1 de la Rapamicina , Aductos de ADN , Ayuno/fisiología
8.
Mol Med ; 30(1): 9, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38216914

RESUMEN

BACKGROUND: Lysine demethylase 5C (KDM5C) has been implicated in the development of several human cancers. This study aims to investigate the role of KDM5C in the progression of colorectal cancer (CRC) and explore the associated molecular mechanism. METHODS: Bioinformatics tools were employed to predict the target genes of KDM5C in CRC. The expression levels of KDM5C and prefoldin subunit 5 (PFDN5) in CRC cells were determined by RT-qPCR and western blot assays. The interaction between KDM5C, H3K4me3, and PFDN5 was validated by chromatin immunoprecipitation. Expression and prognostic values of KDM5C and PFDN5 in CRC were analyzed in a cohort of 72 patients. The function of KDM5C/PFDN5 in c-Myc signal transduction was analyzed by luciferase assay. Silencing of KDM5C and PFDN5 was induced in CRC cell lines to analyze the cell malignant phenotype in vitro and tumorigenic activity in nude mice. RESULTS: KDM5C exhibited high expression, while PFDN5 displayed low expression in CRC cells and clinical CRC samples. High KDM5C levels correlated with poor survival and unfavorable clinical presentation, whereas elevated PFDN5 correlated with improved patient outcomes. KDM5C mediated demethylation of H3K4me3 on the PFDN5 promoter, suppressing its transcription and thereby enhancing the transcriptional activity of c-Myc. KDM5C knockdown in CRC cells suppressed cell proliferation, migration and invasion, epithelial-mesenchymal transition, and tumorigenic activity while increasing autophagy and apoptosis rates. However, the malignant behavior of cells was restored by the further silencing of PFDN5. CONCLUSION: This study demonstrates that KDM5C inhibits PFDN5 transcription, thereby activating c-Myc signal transduction and promoting CRC progression.


Asunto(s)
Neoplasias Colorrectales , Lisina , Chaperonas Moleculares , Animales , Humanos , Ratones , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , Lisina/genética , Lisina/metabolismo , Ratones Desnudos , Procesos Neoplásicos , Transducción de Señal
9.
Biochem Biophys Res Commun ; 704: 149699, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38412668

RESUMEN

With an increasing understanding of the mechanisms of fracture healing, it has been found that nerve injury plays a crucial role in the process, but the specific mechanism is yet to be completely revealed. To address this issue and provide novel insights for fracture treatment, we compiled this review. This review aims to study the impact of nerve injury on fracture healing, exploring the role of neurotrophic factors in the healing process. We first revisited the effects of the central nervous system (CNS) and the peripheral nervous system (PNS) on the skeletal system, and further explained the phenomenon of significantly accelerated fracture healing under nerve injury conditions. Then, from the perspective of neurotrophic factors, we delved into the physiological functions and mechanisms of neurotrophic factors, such as nerve growth factor (NGF), Neuropeptides (NPs), and Brain-derived neurotrophic factor (BDNF), in bone metabolism. These effects include direct actions on bone cells, improvement of local blood supply, regulation of bone growth factors, control of cellular signaling pathways, promotion of callus formation and bone regeneration, and synergistic or antagonistic effects with other endocrine factors, such as Sema3A and Transforming Growth Factor ß (TGF-ß). Finally, we discussed the treatments of fractures with nerve injuries and the future research directions in this review, suggesting that the relationship between nerve injury and fracture healing, as well as the role of nerve injury in other skeletal diseases.


Asunto(s)
Fracturas Óseas , Neuropéptidos , Enfermedades del Sistema Nervioso Periférico , Humanos , Curación de Fractura/fisiología , Regeneración Ósea/fisiología
10.
BMC Plant Biol ; 24(1): 5, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38163899

RESUMEN

Yellow Camellia (Camellia sect. chrysantha) is a rare ornamental plant and an important germplasm resource globally. Camellia nitidissima thrives in normal acidic soils, while Camellia limonia can adapt to the calcareous soils found in karst areas. Our previous study on the karst adaptation of yellow camellias revealed that the expression levels of heat shock protein 20(HSP20) were higher in Camellia limonia than in Camellia nitidissima. However, the functions of the HSP20 gene of Camellia limonia remain unclear to data. In this study, the HSP20 genes of Camellia limonia (ClHSP20-OE lines) and Camellia. nitidissima (CnHSP20-OE lines) were cloned and overexpressed heterologously in Arabidopsis thaliana. Additionally, we overexpressed the HSP20 gene of Arabidopsis (AtHSP20-OE lines) was also overexpressed, and the T-DNA inserted mutants (athspmutant lines) were also used to determine the functions of HSP20 genes. Under high calcium stress, the chlorophyll, nitrogen, water content and humidity of leaves were increased in ClHSP20-OE lines, while those of other lines were declined. The size of the stomatal apertures, stomatal conductance, and the photosynthetic efficiency of ClHSP20-OE lines were higher than those of the other lines. However, the accumulation of H2O2 and O2- in the leaves of ClHSP20-OE lines was the lowest among all the lines. Energy spectrum scanning revealed that the percentage of calcium on the surfaces of the leaves of ClHSP20-OE lines was relatively low, while that of athspmutant lines was the highest. The ClHSP20 gene can also affected soil humidity and the contents of soil nitrogen, phosphorus, and potassium. Transcriptome analysis revealed that the expressions of FBA5 and AT5G10770 in ClHSP20-OE lines was significantly up-regulated compared to that of CnHSP20-OE lines. Compared to that of athspmutant lines, the expressions of DREB1A and AT3G30460 was significantly upregulated in AtHSP20-OE lines, and the expression of POL was down-regulated. Our findings suggest that the HSP20 gene plays a crucial role in maintained photosynthetic rate and normal metabolism by regulating the expression of key genes under high-calcium stress. This study elucidates the mechanisms underlying the karst adaptation in Camellia. limonia and provides novel insights for future research on karst plants.


Asunto(s)
Arabidopsis , Camellia , Camellia/genética , Arabidopsis/genética , Calcio , Proteínas de Choque Térmico/genética , Peróxido de Hidrógeno , Nitrógeno , Suelo , Regulación de la Expresión Génica de las Plantas
11.
Small ; 20(11): e2306972, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38143291

RESUMEN

Vanadium-based compounds are identified as promising cathode materials for aqueous zinc ion batteries due to their high specific capacity. However, the low intrinsic conductivity and sluggish Zn2+ diffusion kinetics seriously impede their further practical application. Here, oxygen vacancies on NH4 V4 O10 is reported as a high-performing cathode material for aqueous zinc ion batteries via a facile hydrothermal strategy. The introduction of oxygen vacancy accelerates the ion and charge transfer kinetics, reduces the diffusion barrier of zinc ions, and establishes a stable crystal structure during zinc ion (de-intercalation). As a result, the oxygen vacancy enriched NH4 V4 O10 exhibits a high specific capacity of ≈499 mA h g-1 at 0.2 A g-1 , an excellent rate capability of 296 mA h g-1 at 10 A g-1 and the specific capacity cycling stability with 95.1% retention at 5 A g-1 for 4000 cycles, superior to the NVO sample (186.4 mAh g-1 at 5 A g-1 , 66% capacity retention).

12.
Small ; 20(10): e2306211, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37875779

RESUMEN

The stability of aqueous Zn-ion batteries (AZIBs) is detrimentally influenced by the formation of Zn dendrites and the occurrence of parasitic side reactions at the Zn metal anode (ZMA)-electrolyte interface. The strategic manipulation of the preferential crystal orientation during Zn2+ plating serves as an essential approach to mitigate this issue. Here, Zn aspartate (Zn-Asp), an electrolyte additive for AZIBs, is introduced not only to optimize the solvation structure of Zn2+ , but also to crucially promote preferential Zn2+ plating on the (002) crystal plane of ZMA. As a result, both side reactions and Zn dendrites are effectively inhibited, ensuring an anode surface free of both dendrites and by-products. The implementation of Zn-Asp leads to significant enhancements in both Zn||Zn symmetric and Zn||Ti batteries, which demonstrate robust cyclability of over 3200 h and high Coulombic efficiency of 99.29%, respectively. Additionally, the Zn||NaV3 O8 ·1.5H2 O full battery exhibits remarkable rate capability, realizing a high capacity of 240.77 mA h g-1 at 5 A g-1 , and retains 92.7% of its initial capacity after 1000 cycles. This research underscores the vital role of electrolyte additives in regulating the preferential crystal orientation of ZMA, thereby contributing to the development of high-performing AZIBs.

13.
Small ; : e2400292, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38659378

RESUMEN

Aqueous Zn batteries employing mildly acidic electrolytes have emerged as promising contenders for safe and cost-effective energy storage solutions. Nevertheless, the intrinsic reversibility of the Zn anode becomes a focal concern due to the involvement of acidic electrolyte, which triggers Zn corrosion and facilitates the deposition of insulating byproducts. Moreover, the unregulated growth of Zn over cycling amplifies the risk of internal short-circuiting, primarily induced by the formation of Zn dendrites. In this study, a class of glucose-derived monomers and a block copolymer are synthesized through a building-block assembly strategy, ultimately leading to uncover the optimal polymer structure that suppresses the Zn corrosion while allowing efficient ion conduction with a substantial contribution from cation transport. Leveraging these advancements, remarkable enhancements are achieved in the realm of Zn reversibility, exemplified by a spectrum of performance metrics, including robust cycling stability without voltage overshoot and short-circuiting during 3000 h of cycling, stable operation at a high depth of charge/discharge of 75% and a high current density, >95% Coulombic efficiency over 2000 cycles, successful translation of the anode improvement to full cell performance. These polymer designs offer a transformative path based on the modular synthesis of polymeric coatings toward highly reversible Zn anode.

14.
J Virol ; 97(11): e0113723, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-37855619

RESUMEN

IMPORTANCE: The ongoing COVID-19 pandemic has been characterized by the emergence of new SARS-CoV-2 variants including the highly transmissible Omicron XBB sublineages, which have shown significant resistance to neutralizing antibodies (nAbs). This resistance has led to decreased vaccine effectiveness and therefore result in breakthrough infections and reinfections, which continuously threaten public health. To date, almost all available therapeutic nAbs, including those authorized under Emergency Use Authorization nAbs that were previously clinically useful against early strains, have recently been found to be ineffective against newly emerging variants. In this study, we provide a comprehensive structural basis about how the Class 3 nAbs, including 1G11 in this study and noted LY-CoV1404, are evaded by the newly emerged SARS-CoV-2 variants.


Asunto(s)
Anticuerpos Neutralizantes , COVID-19 , Pandemias , Humanos , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales , Infección Irruptiva , COVID-19/inmunología , COVID-19/virología
15.
J Transl Med ; 22(1): 401, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38689341

RESUMEN

BACKGROUND: The cancer microbiota was considered the main risk factor for cancer progression. We had proved that Fusobacterium periodonticum (F.p) was higher abundance in Esophageal cancer(EC)tissues. Bioinformation analysis found that BCT was a key virulence protein of F.p. However, little is known about the role and mechanism of BCT in EC. This study aimed to recognize the key virulence protein of F.p and explore the mechanism of BCT in promoting EC. METHODS: We constructed a eukaryotic expression vector and purified the recombinant protein BCT. CCK8 used to analyzed the activity of EC after treated by different concentration of BCT. UPLC-MS/MS and ELISA used to detect the metabonomics and metabolites. The ability of migration and invasion was completed by transwell assay. RT-QPCR, WB used to analyze the expression of relevant genes. RESULTS: Our data showed that BCT was higher expression in EC tumor tissues (p < 0.05) and BCT in 20 µg/mL promoted the survival, invasion and migration of EC cells (EC109) (p < 0.05). Meanwhile, UPLC-MS/MS results suggested that BCT resulted in an augmentation of hypotaurine metabolism, arachidonic acid metabolism, glycolysis/gluconeogenesis, tryptophan metabolism, citrate cycle activity in EC109. The metabolic changes resulted in decreasing in glucose and pyruvate levels but increase in lactate dehydrogenase (LDH) activity and lactic acid (LA) as well as the expression of glucose transporter 1, Hexokinase 2, LDH which regulated the glycolysis were all changed (p < 0.05). The BCT treatment upregulated the expression of TLR4, Akt, HIF-1α (p < 0.05) which regulated the production of LA. Furthermore, LA stimulation promoted the expression of GPR81, Wnt, and ß-catenin (p < 0.05), thereby inducing EMT and metastasis in EC109 cells. CONCLUSION: Altogether, these findings identified that impact of BCT in regulation of glycolysis in EC109 and its involves the TLR4/Akt/HIF-1α pathway. Meanwhile, glycolysis increasing the release of LA and promote the EMT of EC109 by GPR81/Wnt/ß-catenin signaling pathway. In summary, our findings underscore the potential of targeting BCT as an innovative strategy to mitigate the development of EC.


Asunto(s)
Movimiento Celular , Transición Epitelial-Mesenquimal , Neoplasias Esofágicas , Fusobacterium , Glucosa , Ácido Láctico , Humanos , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Ácido Láctico/metabolismo , Línea Celular Tumoral , Glucosa/metabolismo , Fusobacterium/metabolismo , Proteínas Bacterianas/metabolismo , Invasividad Neoplásica , Regulación Neoplásica de la Expresión Génica
16.
BMC Microbiol ; 24(1): 134, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654189

RESUMEN

BACKGROUND: The incidence of exertional heat stroke (EHS) escalates during periods of elevated temperatures, potentially leading to persistent cognitive impairment postrecovery. Currently, effective prophylactic or therapeutic measures against EHS are nonexistent. METHODS: The selection of days 14 and 23 postinduction for detailed examination was guided by TEM of neuronal cells and HE staining of intestinal villi and the hippocampal regions. Fecal specimens from the ileum and cecum at these designated times were analyzed for changes in gut microbiota and metabolic products. Bioinformatic analyses facilitated the identification of pivotal microbial species and metabolites. The influence of supplementing these identified microorganisms on behavioral outcomes and the expression of functional proteins within the hippocampus was subsequently assessed. RESULTS: TEM analyses of neurons, coupled with HE staining of intestinal villi and the hippocampal region, indicated substantial recovery in intestinal morphology and neuronal injury on Day 14, indicating this time point for subsequent microbial and metabolomic analyses. Notably, a reduction in the Lactobacillaceae family, particularly Lactobacillus murinus, was observed. Functional annotation of 16S rDNA sequences suggested diminished lipid metabolism and glycan biosynthesis and metabolism in EHS models. Mice receiving this intervention (EHS + probiotics group) exhibited markedly reduced cognitive impairment and increased expression of BDNF/TrKB pathway molecules in the hippocampus during behavioral assessment on Day 28. CONCLUSION: Probiotic supplementation, specifically with Lactobacillus spp., appears to mitigate EHS-induced cognitive impairment, potentially through the modulation of the BDNF/TrKB signaling pathway within the hippocampus, illustrating the therapeutic potential of targeting the gut-brain axis.


Asunto(s)
Disfunción Cognitiva , Microbioma Gastrointestinal , Golpe de Calor , Animales , Femenino , Masculino , Ratones , Eje Cerebro-Intestino , Disfunción Cognitiva/dietoterapia , Disfunción Cognitiva/etiología , Disfunción Cognitiva/microbiología , Disfunción Cognitiva/psicología , Microbioma Gastrointestinal/fisiología , Golpe de Calor/complicaciones , Golpe de Calor/metabolismo , Golpe de Calor/fisiopatología , Hipocampo/citología , Hipocampo/fisiopatología , Lactobacillus/metabolismo , Neuronas/ultraestructura , Probióticos , Conducta Animal , Ácidos Grasos Volátiles/metabolismo
17.
J Med Virol ; 96(4): e29599, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38647039

RESUMEN

Human immunodeficiency virus (HIV) infection through transfusion has been an imperative challenge for blood safety. Despite the implementation of screening strategies, there was still the residual risk of transfusion-transmitted HIV. Considering that the prevalence of HIV infection in blood donors is significant for evaluating blood safety and potential risks to the population, meta-analysis was applied to investigate the HIV prevalence among voluntary blood donors during the past 27 years to characterize the epidemiology and related risk factors of HIV in blood donors. The literature concerning the HIV screening reactive rate and prevalence in Chinese voluntary blood donors was collected through the systematic searching of four electronic databases. After integrating data, following the Preferred Reporting of Items for Systematic Reviews and Meta-Analyses guidelines, data manipulation and statistical analyses were conducted by Stata 12.0. The results indicated that overall HIV prevalence was 0.0178% (95% confidence interval [CI], 0.0169%-0.0187%) with a remarkable rise, which varied from 2000 (0.0034%) to 2015 (0.027%). The HIV window period infection rate was 0.0475‱ (95% CI, 0.0304‱-0.0646‱). Importantly, subgroup analysis revealed the heterogeneity in gender, occupations, education and donation frequency. With the effective control of HIV transmission through blood, HIV prevalence declined in China to some extent in recent years, and the characteristics of HIV epidemic in some provinces have drastically changed. However, remaining relatively high HIV prevalence and overall increased trend of HIV prevalence since the 21th century demonstrates the potential residual risk of blood transfusion, and the whole society is supposed to pay close attention to HIV infection.


Asunto(s)
Donantes de Sangre , Infecciones por VIH , Humanos , Donantes de Sangre/estadística & datos numéricos , China/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Prevalencia , Factores de Riesgo
18.
Plant Cell Environ ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38808958

RESUMEN

A wide variety of membrane-less organelles in cells play an essential role in regulating gene expression, RNA processing, plant growth and development, and helping organisms cope with changing external environments. In biology, liquid-liquid phase separation (LLPS) usually refers to a reversible process in which one or more specific molecular components are spontaneously separated from the bulk environment, producing two distinct liquid phases: concentrated and dilute. LLPS may be a powerful cellular compartmentalisation mechanism whereby biocondensates formed via LLPS when biomolecules exceed critical or saturating concentrations in the environment where they are found will be generated. It has been widely used to explain the formation of membrane-less organelles in organisms. LLPS studies in the context of plant physiology are now widespread, but most of the research is still focused on non-plant systems; the study of phase separation in plants needs to be more thorough. Proteins and nucleic acids are the main components involved in LLPS. This review summarises the specific features and properties of biomolecules undergoing LLPS in plants. We describe in detail these biomolecules' structural characteristics, the mechanism of formation of condensates, and the functions of these condensates. Finally, We summarised the phase separation mechanisms in plant growth, development, and stress adaptation.

19.
Opt Express ; 32(9): 15136-15146, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38859172

RESUMEN

Surface phonon polaritons (SPhPs) supported by polar dielectrics have been a promising platform for nanophotonics in mid-infrared spectral range. In this work, the temporal dynamic behavior of polar dielectric nanoparticles without (or with) spatial dispersion/nonlocality driven by the ultrashort Gaussian pulses is carried out. We demonstrate that three possible scenarios for the temporal evolutions of the dipole moment including ultrafast oscillations with the decay, exponential decay, and keeping a Gaussian shape exist, when the pulse duration of the incident field is much shorter than, similar to, and much longer than the localized SPhP lifetime. Once the nonlocal effect is considered, the oscillation period becomes large slightly, and the exponential decay turns fast. Furthermore, nonlocality-induced novel temporal behavior is found such as the decay with long-period oscillations when the center frequency of the incident pulse lies at the frequency of adjacent longitudinal resonant modes. The positive and negative time-shifts of the dielectric response reveal that the excitation of the dipole moment will be delayed or advanced. These temporal evolutions can pave the way towards potential applications in the modulation of ultrafast signals for the mid-infrared optoelectronic nanodevices.

20.
Cancer Cell Int ; 24(1): 119, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38553712

RESUMEN

OBJECTIVE: This study aimed to construct a model based on 23 enrolled molecules to evaluate prognoses of pT2/3N0M0 esophageal squamous cell carcinoma (ESCC) patients with up to 20 years of follow-up. METHODS: The lasso-Cox model was used to identify the candidate molecule. A nomogram was conducted to develop the survival model (molecular score, MS) based on the molecular features. Cox regression and Kaplan-Meier analysis were used in this study. The concordance index (C-index) was measured to compare the predicted ability between different models. The primary endpoint was overall survival (OS). RESULTS: A total of 226 patients and 23 proteins were enrolled in this study. Patients were classified into high-risk (MS-H) and low-risk (MS-L) groups based on the MS score of 227. The survival curves showed that the MS-L cohort had better 5-year and 10-year survival rates than the MS-H group (5-year OS: 51.0% vs. 8.0%; 10-year OS: 45.0% vs. 5.0%, all p < 0.001). Furthermore, multivariable analysis confirmed MS as an independent prognostic factor after eliminating the confounding factors (Hazard ratio 3.220, p < 0.001). The pT classification was confirmed to differentiate ESCC patients' prognosis (Log-rank: p = 0.029). However, the combination of pT and MS could classify survival curves evidently (overall p < 0.001), which showed that the prognostic prediction efficiency was improved significantly by the combination of the pT and MS than by the classical pT classification (C-index: 0.656 vs. 0.539, p < 0.001). CONCLUSIONS: Our study suggested an MS for significant clinical stratification of T2/3N0M0 ESCC patients to screen out subgroups with poor prognoses. Besides, the combination of pT staging and MS could predict survival more accurately for this cohort than the pT staging system alone.

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