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1.
BMC Biol ; 22(1): 96, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38679748

RESUMEN

BACKGROUND: The early Cambrian arthropod clade Megacheira, also referred to as great appendage arthropods, comprised a group of diminutive and elongated predators during the early Palaeozoic era, around 518 million years ago. In addition to those identified in the mid-Cambrian Burgess Shale biota, numerous species are documented in the renowned 518-million-year-old Chengjiang biota of South China. Notably, one species, Tanglangia longicaudata, has remained inadequately understood due to limited available material and technological constraints. In this study, we, for the first time, examined eight fossil specimens (six individuals) utilizing state-of-the-art µCT and computer-based 3D rendering techniques to unveil the hitherto hidden ventral and appendicular morphology of this species. RESULTS: We have identified a set of slender endopodites gradually narrowing distally, along with a leaf-shaped exopodite adorned with fringed setae along its margins, and a small putative exite attached to the basipodite. Our techniques have further revealed the presence of four pairs of biramous appendages in the head, aligning with the recently reported six-segmented head in other early euarthropods. Additionally, we have discerned two peduncle elements for the great appendage. These findings underscore that, despite the morphological diversity observed in early euarthropods, there exists similarity in appendicular morphology across various groups. In addition, we critically examine the existing literature on this taxon, disentangling previous mislabelings, mentions, descriptions, and, most importantly, illustrations. CONCLUSIONS: The µCT-based investigation of fossil material of Tanglangia longicaudata, a distinctive early Cambrian euarthropod from the renowned Chengjiang biota, enhances our comprehensive understanding of the evolutionary morphology of the Megacheira. Its overall morphological features, including large cup-shaped eyes, raptorial great appendages, and a remarkably elongated telson, suggest its potential ecological role as a crepuscular predator and adept swimmer in turbid waters.


Asunto(s)
Artrópodos , Fósiles , Animales , Fósiles/anatomía & histología , Artrópodos/anatomía & histología , China , Evolución Biológica , Biota , Microtomografía por Rayos X
2.
J Cogn Neurosci ; : 1-14, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38940732

RESUMEN

Our perception of objects depends on non-oculomotor depth cues, such as pictorial distance cues and binocular disparity, and oculomotor depth cues, such as vergence and accommodation. Although vergence eye movements are always involved in perceiving real distance, previous studies have mainly focused on the effect of oculomotor state via "proprioception" on distance and size perception. It remains unclear whether the oculomotor command of vergence eye movement would also influence visual processing. To address this question, we placed a light at 28.5 cm and a screen for stimulus presentation at 57 cm from the participants. In the NoDivergence condition, participants were asked to maintain fixation on the light regardless of stimulus presentation throughout the trial. In the WithDivergence condition, participants were instructed to initially maintain fixation on the near light and then turn their two eyes outward to look at the stimulus on the far screen. The stimulus was presented for 100 msec, entirely within the preparation stage of the divergence eye movement. We found that participants perceived the stimulus as larger but were less sensitive to stimulus sizes in the WithDivergence condition than in the NoDivergence condition. The earliest visual evoked component C1 (peak latency 80 msec), which varied with stimulus size in the NoDivergence condition, showed similar amplitudes for larger and smaller stimuli in the WithDivergence condition. These results show that vergence eye movement planning affects the earliest visual processing and size perception, and demonstrate an example of the effect of motor command on sensory processing.

3.
Microb Pathog ; 192: 106681, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38754565

RESUMEN

Tuberculosis (TB) is a major fatal infectious disease globally, exhibiting high morbidity rates and impacting public health and other socio-economic factors. However, some individuals are resistant to TB infection and are referred to as "Resisters". Resisters remain uninfected even after exposure to high load of Mycobacterium tuberculosis (Mtb). To delineate this further, this study aimed to investigate the factors and mechanisms influencing the Mtb resistance phenotype. We assayed the phagocytic capacity of peripheral blood mononuclear cells (PBMCs) collected from Resisters, patients with latent TB infection (LTBI), and patients with active TB (ATB), following infection with fluorescent Mycobacterium bovis Bacillus Calmette-Guérin (BCG). Phagocytosis was stronger in PBMCs from ATB patients, and comparable in LTBI patients and Resisters. Subsequently, phagocytes were isolated and subjected to whole transcriptome sequencing and small RNA sequencing to analyze transcriptional expression profiles and identify potential targets associated with the resistance phenotype. The results revealed that a total of 277 mRNAs, 589 long non-coding RNAs, 523 circular RNAs, and 35 microRNAs were differentially expressed in Resisters and LTBI patients. Further, the endogenous competitive RNA (ceRNA) network was constructed from differentially expressed genes after screening. Bioinformatics, statistical analysis, and quantitative real-time polymerase chain reaction were used for the identification and validation of potential crucial targets in the ceRNA network. As a result, we obtained a ceRNA network that contributes to the resistance phenotype. TCONS_00034796-F3, ENST00000629441-DDX43, hsa-ATAD3A_0003-CYP17A1, and XR_932996.2-CERS1 may be crucial association pairs for resistance to TB infection. Overall, this study demonstrated that the phagocytic capacity of PBMCs was not a determinant of the resistance phenotype and that some non-coding RNAs could be involved in the natural resistance to TB infection through a ceRNA mechanism.


Asunto(s)
Leucocitos Mononucleares , MicroARNs , Mycobacterium tuberculosis , Fagocitos , Fagocitosis , Tuberculosis , Humanos , Fagocitos/metabolismo , Fagocitos/inmunología , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/inmunología , Tuberculosis/genética , Tuberculosis/microbiología , Tuberculosis/inmunología , Fagocitosis/genética , MicroARNs/genética , MicroARNs/metabolismo , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Masculino , Adulto , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Femenino , Transcriptoma/genética , Tuberculosis Latente/genética , Tuberculosis Latente/inmunología , Tuberculosis Latente/microbiología , Resistencia a la Enfermedad/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Mycobacterium bovis/inmunología , Persona de Mediana Edad , Biología Computacional/métodos , Adulto Joven , ARN Endógeno Competitivo
4.
BMC Pulm Med ; 24(1): 100, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38413948

RESUMEN

OBJECTIVES: Tuberculosis (TB) is a significant global health concern, given its high rates of morbidity and mortality. The diagnosis using urine lipoarabinomannan (LAM) primarily benefits HIV co-infected TB patients with low CD4 counts. The focus of this study was to develop an ultra-sensitive LAM assay intended for diagnosing tuberculosis across a wider spectrum of TB patients. DESIGN & METHODS: To heighten the sensitivity of the LAM assay, we employed high-affinity rabbit monoclonal antibodies and selected a highly sensitive chemiluminescence LAM assay (CLIA-LAM) for development. The clinical diagnostic criteria for active TB (ATB) were used as a control. A two-step sample collection process was implemented, with the cutoff determined initially through a ROC curve. Subsequently, additional clinical samples were utilized for the validation of the assay. RESULTS: In the assay validation phase, a total of 87 confirmed active TB patients, 19 latent TB infection (LTBI) patients, and 104 healthy control samples were included. Applying a cutoff of 1.043 (pg/mL), the CLIA-LAM assay demonstrated a sensitivity of 55.2% [95%CI (44.13%~65.85%)], and a specificity of 100% [95%CI (96.52%~100.00%)], validated against clinical diagnostic results using the Mann-Whitney U test. Among 11 hematogenous disseminated TB patients, the positive rate was 81.8%. Importantly, the CLIA-LAM assay consistently yielded negative results in the 19 LTBI patients. CONCLUSION: Overall, the combination of high-affinity antibodies and the CLIA method significantly improved the sensitivity and specificity of the LAM assay. It can be used for the diagnosis of active TB, particularly hematogenous disseminated TB.


Asunto(s)
Infecciones por VIH , Tuberculosis Latente , Tuberculosis Miliar , Humanos , Luminiscencia , Infecciones por VIH/complicaciones , Sensibilidad y Especificidad , Tuberculosis Latente/diagnóstico , Lipopolisacáridos
5.
Clin Infect Dis ; 77(2): 203-211, 2023 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-37072937

RESUMEN

BACKGROUND: The effectiveness and sustainability of masking policies as a pandemic control measure remain uncertain. Our aim was to evaluate different masking policy types on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incidence and to identify factors and conditions impacting effectiveness. METHODS: Nationwide, retrospective cohort study of US counties from 4/4/2020-28/6/2021. Policy impacts were estimated using interrupted time-series models with the masking policy change date (eg, recommended-to-required, no-recommendation-to-recommended, no-recommendation-to-required) modeled as the interruption. The primary outcome was change in SARS-CoV-2 incidence rate during the 12 weeks after the policy change; results were stratified by coronavirus disease 2019 (COVID-19) risk level. A secondary analysis was completed using adult vaccine availability as the policy change. RESULTS: In total, N = 2954 counties were included (2304 recommended-to-required, 535 no-recommendation-to-recommended, 115 no-recommendation-to-required). Overall, indoor mask mandates were associated with 1.96 fewer cases/100 000/week (cumulative reduction of 23.52/100 000 residents during the 12 weeks after policy change). Reductions were driven by communities with critical and extreme COVID-19 risk, where masking mandated policies were associated with an absolute reduction of 5 to 13.2 cases/100 000 residents/week (cumulative reduction of 60 to 158 cases/100 000 residents over 12 weeks). Impacts in low- and moderate-risk counties were minimal (<1 case/100 000 residents/week). After vaccine availability, mask mandates were not associated with significant reductions at any risk level. CONCLUSIONS: Masking policy had the greatest impact when COVID-19 risk was high and vaccine availability was low. When transmission risk decreases or vaccine availability increases, the impact was not significant regardless of mask policy type. Although often modeled as having a static impact, masking policy effectiveness may be dynamic and condition dependent.


Asunto(s)
COVID-19 , Adulto , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Estudios Retrospectivos , Pandemias/prevención & control , Políticas
6.
BMC Infect Dis ; 23(1): 834, 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-38012543

RESUMEN

INTRODUCTION: The urgent need for new treatments for multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is evident. However, the classic randomized controlled trial (RCT) approach faces ethical and practical constraints, making alternative research designs and treatment strategies necessary, such as single-arm trials and host-directed therapies (HDTs). METHODS: Our study adopts a randomized withdrawal trial design for MDR-TB to maximize resource allocation and better mimic real-world conditions. Patients' treatment regimens are initially based on drug resistance profiles and patient's preference, and later, treatment-responsive cases are randomized to different treatment durations. Alongside, a single-arm trial is being conducted to evaluate the potential of sulfasalazine (SASP) as an HDT for pre-XDR-TB, as well as another short-course regimen without HDT for pre-XDR-TB. Both approaches account for the limitations in second-line anti-TB drug resistance testing in various regions. DISCUSSION: Although our study designs may lack the internal validity commonly associated with RCTs, they offer advantages in external validity, feasibility, and ethical appropriateness. These designs align with real-world clinical settings and also open doors for exploring alternative treatments like SASP for tackling drug-resistant TB forms. Ultimately, our research aims to strike a balance between scientific rigor and practical utility, offering valuable insights into treating MDR-TB and pre-XDR-TB in a challenging global health landscape. In summary, our study employs innovative trial designs and treatment strategies to address the complexities of treating drug-resistant TB, fulfilling a critical gap between ideal clinical trials and the reality of constrained resources and ethical considerations. TRAIL REGISTRATION: Chictr.org.cn, ChiCTR2100045930. Registered on April 29, 2021.


Asunto(s)
Tuberculosis Extensivamente Resistente a Drogas , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Antituberculosos/efectos adversos , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Protocolos Clínicos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
7.
Phys Chem Chem Phys ; 25(29): 19795-19803, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37449881

RESUMEN

As one of the promising next-generation energy storage systems, lithium-sulfur (Li-S) batteries have been the subject of much recent attention. However, the polysulfide shuttle effect remains problematic owing to the dissolution of intermediate polysulfide species in the electrolyte and the sluggish reaction dynamics in Li-S batteries. To overcome these issues, this work reports an effective strategy for enhancing the electrochemical performance of Li-S batteries using single atom Zn doping on the S-terminated Ti2C MXenes (Ti2-xZnxCS2). Spin-polarized density functional theory (DFT) calculations were performed to elucidate the interactions of lithium polysulfides (LiPSs) and the Ti2-xZnxCS2 surface in terms of geometric and electronic properties, as well as the delithiation process of Li2S on the Ti2-xZnxCS2 surface. It is found that doping single atom Zn could induce a new Lewis acid-based sites, which could provide proper affinity toward LiPSs. Combined with the metallic character, a low Li diffusion barrier and high catalytic activity for the delithiation process of Li2S, makes Ti2-xZnxCS2 a promising cathode material for Li-S batteries. The results demonstrate the importance of surface chemistry and the electronic structure of MXenes in LiPSs' adsorption and catalysis capability. We believe that our findings provide insights into the recent experimental results and guidance for the preparation and practical application of MXenes in Li-S batteries.

8.
Proc Natl Acad Sci U S A ; 117(48): 30836-30847, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-33199608

RESUMEN

Figure-ground modulation, i.e., the enhancement of neuronal responses evoked by the figure relative to the background, has three complementary components: edge modulation (boundary detection), center modulation (region filling), and background modulation (background suppression). However, the neuronal mechanisms mediating these three modulations and how they depend on awareness remain unclear. For each modulation, we compared both the cueing effect produced in a Posner paradigm and fMRI blood oxygen-level dependent (BOLD) signal in primary visual cortex (V1) evoked by visible relative to invisible orientation-defined figures. We found that edge modulation was independent of awareness, whereas both center and background modulations were strongly modulated by awareness, with greater modulations in the visible than the invisible condition. Effective-connectivity analysis further showed that the awareness-dependent region-filling and background-suppression processes in V1 were not derived through intracortical interactions within V1, but rather by feedback from the frontal eye field (FEF) and dorsolateral prefrontal cortex (DLPFC), respectively. These results indicate a source for an awareness-dependent figure-ground segregation in human prefrontal cortex.


Asunto(s)
Concienciación , Corteza Prefrontal/fisiología , Percepción Visual , Mapeo Encefálico , Conectoma , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Reconocimiento Visual de Modelos , Estimulación Luminosa , Corteza Prefrontal/diagnóstico por imagen , Corteza Visual/diagnóstico por imagen , Corteza Visual/fisiología
9.
J Neurosci ; 41(46): 9593-9607, 2021 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-34611027

RESUMEN

Although bottom-up attention can improve visual performance with and without awareness to the exogenous cue, whether they are governed by a common neural computation remains unclear. Using a modified Posner paradigm with backward masking, we found that the cueing effect displayed a monotonic gradient profile (Gaussian-like), both with and without awareness, whose scope, however, was significantly wider with than without awareness. This awareness-dependent scope offered us a unique opportunity to change the relative size of the attention field to the stimulus, differentially modulating the gain of attentional selection, as proposed by the normalization model of attention. Therefore, for each human subject (male and female), the stimulus size was manipulated as their respective mean attention fields with and without awareness while stimulus contrast was varied in a spatial cueing task. By measuring the gain pattern of contrast-response functions on the spatial cueing effect derived by visible or invisible cues, we observed changes in the cueing effect consonant with changes in contrast gain for visible cues and response gain for invisible cues. Importantly, a complementary analysis confirmed that subjects' awareness-dependent attention fields can be simulated by using the normalization model of attention. Together, our findings indicate an awareness-dependent normalization framework of visual bottom-up attention, placing a necessary constraint, namely, awareness, on our understanding of the neural computations underlying visual attention.SIGNIFICANCE STATEMENT Bottom-up attention is known to improve visual performance with and without awareness. We discovered that manipulating subjects' awareness can modulate their attention fields of visual bottom-up attention, which offers a unique opportunity to regulate its normalization processes. On the one hand, by measuring the gain pattern of contrast-response functions on the spatial cueing effect derived by visible or invisible cues, we observed changes in the cueing effect consonant with changes in contrast gain for visible cues and response gain for invisible cues. On the other hand, by using the normalization model of attention, subjects' awareness-dependent attention fields can be simulated successfully. Our study supports important predictions of the normalization model of visual bottom-up attention and further reveals its dependence on awareness.


Asunto(s)
Atención/fisiología , Concienciación/fisiología , Modelos Neurológicos , Percepción Visual/fisiología , Adulto , Señales (Psicología) , Femenino , Humanos , Masculino
10.
BMC Genomics ; 23(Suppl 1): 311, 2022 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-35439939

RESUMEN

BACKGROUND: Deep-sea mussels living in the cold seeps with enormous biomass act as the primary consumers. They are well adapted to the extreme environment where light is absent, and hydrogen sulfide, methane, and other hydrocarbon-rich fluid seepage occur. Despite previous studies on diversity, role, evolution, and symbiosis, the changing adaptation patterns during different developmental stages of the deep-sea mussels remain largely unknown. RESULTS: The deep-sea mussels (Bathymodiolus platifrons) of two developmental stages were collected from the cold seep during the ocean voyage. The gills, mantles, and adductor muscles of these mussels were used for the Illumina sequencing. A total of 135 Gb data were obtained, and subsequently, 46,376 unigenes were generated using de-novo assembly strategy. According to the gene expression analysis, amounts of genes were most actively expressed in the gills, especially genes involved in environmental information processing. Genes encoding Toll-like receptors and sulfate transporters were up-regulated in gills, indicating that the gill acts as both intermedium and protective screen in the deep-sea mussel. Lysosomal enzymes and solute carrier responsible for nutrients absorption were up-regulated in the older mussel, while genes related to toxin resistance and autophagy were up-regulated in the younger one, suggesting that the older mussel might be in a vigorous stage while the younger mussel was still paying efforts in survival and adaptation. CONCLUSIONS: In general, our study suggested that the adaptation capacity might be formed gradually during the development of deep-sea mussels, in which the gill and the symbionts play essential roles.


Asunto(s)
Mytilidae , Transcriptoma , Animales , Branquias/metabolismo , Metano/metabolismo , Simbiosis
11.
Neuroimage ; 247: 118864, 2022 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-34965453

RESUMEN

The allocation of exogenously cued spatial attention is governed by a saliency map. Yet, how salience is mapped when multiple salient stimuli are present simultaneously, and how this mapping interacts with awareness remains unclear. These questions were addressed here using either visible or invisible displays presenting two foreground stimuli (whose bars were oriented differently from the bars in the otherwise uniform background): a high salience target and a distractor of varied, lesser salience. Interference, or not, by the distractor with the effective salience of the target served to index a graded or non-graded nature of salience mapping, respectively. The invisible and visible displays were empirically validated by a two-alternative forced choice test (detecting the quadrant of the target) demonstrating subjects' performance at or above chance level, respectively. By combining psychophysics, fMRI, and effective connectivity analysis, we found a graded distribution of salience with awareness, changing to a non-graded distribution without awareness. Crucially, we further revealed that the graded distribution was contingent upon feedback from the posterior intraparietal sulcus (pIPS, especially from the right pIPS), whereas the non-graded distribution was innate to V1. Together, this awareness-dependent mapping of saliency reconciles several previous, seemingly contradictory findings regarding the nature of the saliency map.


Asunto(s)
Concienciación/fisiología , Imagen por Resonancia Magnética/métodos , Desempeño Psicomotor/fisiología , Corteza Visual/fisiología , Percepción Visual/fisiología , Adulto , Femenino , Fijación Ocular , Voluntarios Sanos , Humanos , Masculino , Estimulación Luminosa
12.
Cell Tissue Res ; 388(3): 549-563, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35347409

RESUMEN

Mesenchymal stem cells (MSCs) have shown great potential in treating autoimmune diseases due to their immunomodulatory capability, which has been verified in both animal experiments and clinical trials. Psoriasis is a chronic and remitting immune-related disease. Limited studies have demonstrated that MSCs might be an effective therapeutic approach for managing psoriasis, whose underlying mechanism remains to be elucidated. In our present study, human umbilical cord-derived MSCs (hUC-MSCs) were subcutaneously injected into mice with imiquimod (IMQ)-induced psoriasis-like skin inflammation to explore the feasibility of this cellular therapy. The severity of psoriasis-like dermatitis was evaluated by cumulative psoriasis area and severity index score and epidermal thickness of skin tissue sections. Flow cytometric analysis was utilized to detect T helper cells, regulatory T cells, and γδ T cells in skin-draining lymph nodes. Real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to assess the expression levels of psoriasis-related cytokines and chemokines in mouse dorsal skin lesions. We discovered that hUC-MSCs drastically diminished the severity of IMQ-induced psoriasis-like dermatitis and suppressed inflammatory cell response. Although the tail vein injection of hUC-MSCs was also effective, it was correlated with higher mortality owing to pulmonary embolism. By comparison, subcutaneous injection with two million hUC-MSCs was identified to be the optimal therapeutic strategy. Furthermore, we uncovered that hUC-MSCs might repress skin inflammation probably through inhibiting interleukin-17-producing γδ T cells. In conclusion, subcutaneous administration of hUC-MSCs might be a promising therapeutic approach for psoriasis. Our findings provide novel insights into the underpinning mechanism of hUC-MSC treatment in the management of psoriasis.


Asunto(s)
Dermatitis , Interleucina-17/metabolismo , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Psoriasis , Animales , Dermatitis/metabolismo , Humanos , Imiquimod/efectos adversos , Imiquimod/metabolismo , Inflamación/patología , Células Madre Mesenquimatosas/metabolismo , Ratones , Psoriasis/inducido químicamente , Psoriasis/terapia , Linfocitos T/metabolismo , Cordón Umbilical
13.
Exp Dermatol ; 31(4): 594-599, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34717022

RESUMEN

Erythrokeratodermia variabilis et progressiva (EKVP) is a rare genodermatosis of clinical and genetic heterogeneity, characterized by the manifestations of localized or disseminated persistent hyperkeratotic plagues and stationary to migratory transient erythematous patches. The majority of EKVP cases display an autosomal dominant mode of inheritance with incomplete penetrance, although recessive transmission has also been described. Mutations associated with EKVP have been primarily detected in connexin (Cx) genes. We herein reported a Chinese sporadic case of late-onset EKVP with a novel heterozygous missense mutation c.109G>A (p.V37M) in GJB4 (Cx30.3) gene, which resulted in a significant reduction of GJB4 expression in the epidermis of the patient. In accordance, while wild-type GJB4 localized at the cell membrane of HeLa cells forming intercellular junctions and intracellular puncta, V37M mutant variant was diffusely expressed within HeLa cells at a considerably lower level. Our findings reveal an essential role of GJB4 in the pathogenesis of EKVP and provides insights into the therapeutic potential of the disease.


Asunto(s)
Conexinas , Eritroqueratodermia Variable , Conexinas/genética , Eritroqueratodermia Variable/genética , Eritroqueratodermia Variable/patología , Células HeLa , Heterocigoto , Humanos , Mutación Missense
14.
Med Sci Monit ; 28: e937081, 2022 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-35854639

RESUMEN

BACKGROUND LIM domain proteins play crucial roles in tumors by interacting with diverse proteins. However, their roles in the course of colorectal mucosa-adenoma-carcinoma remain unclear. This study aimed to depict their dynamic expression profiles and elucidate their potential functions in this transition course. MATERIAL AND METHODS Differentially-expressed LIM proteins (DELGs) in paired adenomas, carcinomas, and mucosae were identified using the GEO dataset (GSE 117606) and validated by immunohistochemistry using our tissue microarray. Kaplan-Meier survival analysis, WGCNA, module-trait analysis, and KEGG enrichment were conducted. The correlation of DELGs expression levels with immune infiltration was assessed using the ESTIMATE package and TISCH database. The role of DELGs of interest was validated using cell proliferation, migration, and invasion assays. RESULTS Four DELGs were identified - LMO3, FHL1, NEBL, and TGFB1I1 - all of which were of significance in prognosis. Module-trait correlation and KEGG enrichment revealed their involvement in cancer-related signaling. Immunohistochemistry showed gradual downregulation of LMO3 but upregulation of NEBL in the mucosa-adenoma-carcinoma sequence. The opposite expression patterns were observed for FHL1 and TGFB1I1 in tumor epithelium and mesenchyme. High expression levels of the DELGs were correlated with increased infiltration of NK, NKT, and macrophages, except for NEBL. Importantly, LMO3 inhibited proliferation, migration, and invasion of colon epithelial cells. CONCLUSIONS This study identified 4 differentially-expressed LIM genes - LMO3, FHL1, TGFB1I1, and NEBL - and revealed they were involved in the mucosa-adenoma-carcinoma sequence via regulating cancer-related pathways, influencing epigenetic field, or affecting immune infiltration. Our findings provide new insights into the roles of LIM proteins in the course of mucosa-adenoma-carcinoma.


Asunto(s)
Adenoma , Neoplasias Colorrectales , Proteínas con Dominio LIM , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adenoma/genética , Adenoma/metabolismo , Adenoma/patología , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Biología Computacional/métodos , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas con Dominio LIM/genética , Proteínas con Dominio LIM/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo
15.
Mol Cancer ; 20(1): 121, 2021 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-34560891

RESUMEN

N6-methyladenosine (m6A) is a prevalent internal modification in eukaryotic RNAs regulated by the so-called "writers", "erasers", and "readers". m6A has been demonstrated to exert critical molecular functions in modulating RNA maturation, localization, translation and metabolism, thus playing an essential role in cellular, developmental, and disease processes. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed single-stranded structures generated by back-splicing. CircRNAs also participate in physiological and pathological processes through unique mechanisms. Despite their discovery several years ago, m6A and circRNAs has drawn increased research interest due to advances in molecular biology techniques these years. Recently, several scholars have investigated the crosstalk between m6A and circRNAs. In this review, we provide an overview of the current knowledge of m6A and circRNAs, as well as summarize the crosstalk between these molecules based on existing research. In addition, we present some suggestions for future research perspectives.


Asunto(s)
Adenosina/análogos & derivados , Regulación de la Expresión Génica , ARN Circular/genética , ARN Circular/metabolismo , Adenosina/metabolismo , Humanos , Metilación , Biosíntesis de Proteínas , Empalme del ARN , Estabilidad del ARN , Transporte de ARN , Transcripción Genética
16.
PLoS Biol ; 16(6): e2005399, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29939981

RESUMEN

Feature-based attention has a spatially global effect, i.e., responses to stimuli that share features with an attended stimulus are enhanced not only at the attended location but throughout the visual field. However, how feature-based attention modulates cortical neural responses at unattended locations remains unclear. Here we used functional magnetic resonance imaging (fMRI) to examine this issue as human participants performed motion- (Experiment 1) and color- (Experiment 2) based attention tasks. Results indicated that, in both experiments, the respective visual processing areas (middle temporal area [MT+] for motion and V4 for color) as well as early visual, parietal, and prefrontal areas all showed the classic feature-based attention effect, with neural responses to the unattended stimulus significantly elevated when it shared the same feature with the attended stimulus. Effective connectivity analysis using dynamic causal modeling (DCM) showed that this spatially global effect in the respective visual processing areas (MT+ for motion and V4 for color), intraparietal sulcus (IPS), frontal eye field (FEF), medial frontal gyrus (mFG), and primary visual cortex (V1) was derived by feedback from the inferior frontal junction (IFJ). Complementary effective connectivity analysis using Granger causality modeling (GCM) confirmed that, in both experiments, the node with the highest outflow and netflow degree was IFJ, which was thus considered to be the source of the network. These results indicate a source for the spatially global effect of feature-based attention in the human prefrontal cortex.


Asunto(s)
Corteza Prefrontal/fisiología , Adulto , Atención/fisiología , Mapeo Encefálico , Percepción de Color/fisiología , Conectoma , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Modelos Neurológicos , Modelos Psicológicos , Percepción de Movimiento/fisiología , Estimulación Luminosa , Corteza Visual/fisiología , Campos Visuales/fisiología , Adulto Joven
17.
Inorg Chem ; 60(21): 16538-16543, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34637295

RESUMEN

Exploring new excellent electrocatalysts for the hydrogen evolution reaction (HER) is of significance for the development of hydrogen energy. Herein, a ternary chalcogenide (Pt3Pb2S2) is successfully designed and synthesized using layered PtS2 as a matrix. The energy level of the Pt 5d orbital is upshifted to the Fermi surface after replacing S atoms by Pb atoms, which results in the high conductivity of Pt3Pb2S2. In addition, the low-coordinated Pt atoms inserted in the voids of [Pt2Pb2S2] layers have a lower free energy of H* adsorption than do metallic Pt atoms, which endows Pt3Pb2S2 with excellent HER performance. The overpotential and Tafel slope of Pt3Pb2S2 toward HER activity are measured to be 43 mV at 10 mA cm-2 and 43 mV dec-1, respectively. More importantly, Pt3Pb2S2 shows high intrinsic HER catalytic activity and long-term stability. This work provides a promising strategy for designing novel excellent transition-metal chalcogenide electrocatalysts.

18.
Int J Med Sci ; 18(9): 1935-1945, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33850462

RESUMEN

The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains makes disease control more complicated, which is the main cause of death in tuberculosis (TB) patients. Early detection and timely standard treatment are the key to current prevention and control of drug-resistant TB. In recent years, despite the continuous advancement in drug-resistant TB diagnostic technology, the needs for clinical rapid and accurate diagnosis are still not fully met. With the development of sequencing technology, the research of human microecology has been intensified. This study aims to use 16 rRNA sequencing technology to detect and analyze upper respiratory flora of TB patients with anti-TB drug sensitivity (DS, n = 55), monoresistance isoniazide (MR-INH, n = 33), monoresistance rifampin (MR-RFP, n = 12), multidrug resistance (MDR, n = 26) and polyresistance (PR, n = 39) in southern China. Potential microbial diagnostic markers for different types of TB drug resistance are searched by screening differential flora, which provides certain guiding significance for drug resistance diagnosis and clinical drug use of TB. The results showed that the pulmonary microenvironment of TB patients was more susceptible to infection by external pathogens, and the infection of different drug-resistant Mtb leads to changes in different flora. Importantly, seven novel microorganisms (Leptotrichia, Granulicatella, Campylobacter, Delfitia, Kingella, Chlamydophila, Bordetella) were identified by 16S rRNA sequencing as diagnostic markers for different drug resistance types of TB. Leptotrichia, Granulicatella, Campylobacter were potential diagnostic marker for TB patients with INH single-resistance. Delftia was a potential diagnostic marker for TB patients with RFP single drug-resistance. Kingella and Chlamydophila can be used as diagnostic markers for TB patients with PR. Bordetella can be used as a potential diagnostic marker for identification of TB patients with MDR.


Asunto(s)
Antituberculosos/farmacología , Microbiota , Esputo/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Pulmonar/diagnóstico , Adolescente , Adulto , Anciano , Antituberculosos/uso terapéutico , ADN Bacteriano/aislamiento & purificación , Femenino , Humanos , Isoniazida/farmacología , Isoniazida/uso terapéutico , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/crecimiento & desarrollo , ARN Ribosómico 16S/genética , Rifampin/farmacología , Rifampin/uso terapéutico , Sensibilidad y Especificidad , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto Joven
19.
Sensors (Basel) ; 21(15)2021 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-34372326

RESUMEN

As a powerful in situ detection technique, Raman spectroscopy is becoming a popular underwater investigation method, especially in deep-sea research. In this paper, an easy-to-operate underwater Raman system with a compact design and competitive sensitivity is introduced. All the components, including the optical module and the electronic module, were packaged in an L362 × Φ172 mm titanium capsule with a weight of 20 kg in the air (about 12 kg in water). By optimising the laser coupling mode and focusing lens parameters, a competitive sensitivity was achieved with the detection limit of SO42- being 0.7 mmol/L. The first sea trial was carried out with the aid of a 3000 m grade remotely operated vehicle (ROV) "FCV3000" in October 2018. Over 20,000 spectra were captured from the targets interested, including methane hydrate, clamshell in the area of cold seep, and bacterial mats around a hydrothermal vent, with a maximum depth of 1038 m. A Raman peak at 2592 cm-1 was found in the methane hydrate spectra, which revealed the presence of hydrogen sulfide in the seeping gas. In addition, we also found sulfur in the bacterial mats, confirming the involvement of micro-organisms in the sulfur cycle in the hydrothermal field. It is expected that the system can be developed as a universal deep-sea survey and detection equipment in the near future.


Asunto(s)
Respiraderos Hidrotermales , Bacterias , Metano , Espectrometría Raman
20.
Int J Mol Sci ; 22(19)2021 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-34639136

RESUMEN

BACKGROUND: α-cyclodextrin (α-CD) is one of the dietary fibers that may have a beneficial effect on cholesterol and/or glucose metabolism, but its efficacy and mode of action remain unclear. METHODS: In the present study, we examined the anti-hyperglycemic effect of α-CD after oral loading of glucose and liquid meal in mice. RESULTS: Administration of 2 g/kg α-CD suppressed hyperglycemia after glucose loading, which was associated with increased glucagon-like peptide 1 (GLP-1) secretion and enhanced hepatic glucose sequestration. By contrast, 1 g/kg α-CD similarly suppressed hyperglycemia, but without increasing secretions of GLP-1 and insulin. Furthermore, oral α-CD administration disrupts lipid micelle formation through its inclusion of lecithin in the gut luminal fluid. Importantly, prior inclusion of α-CD with lecithin in vitro nullified the anti-hyperglycemic effect of α-CD in vivo, which was associated with increased intestinal mRNA expressions of SREBP2-target genes (Ldlr, Hmgcr, Pcsk9, and Srebp2). CONCLUSIONS: α-CD elicits its anti-hyperglycemic effect after glucose loading by inducing lecithin inclusion in the gut lumen and activating SREBP2, which is known to induce cholecystokinin secretion to suppress hepatic glucose production via a gut/brain/liver axis.


Asunto(s)
Tracto Gastrointestinal/metabolismo , Hiperglucemia/prevención & control , Lecitinas/metabolismo , Periodo Posprandial , Canales de Potasio de Rectificación Interna/fisiología , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , alfa-Ciclodextrinas/farmacología , Animales , Tracto Gastrointestinal/efectos de los fármacos , Hiperglucemia/etiología , Hiperglucemia/metabolismo , Hiperglucemia/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética
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