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2.
Front Microbiol ; 15: 1358752, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873147

RESUMO

Candida albicans (C. albicans), a microbe commonly isolated from Candida vaginitis patients with vaginal tract infections, transforms from yeast to hyphae and produces many toxins, adhesins, and invasins, as well as C. albicans biofilms resistant to antifungal antibiotic treatment. Effective agents against this pathogen are urgently needed. Antimicrobial peptides (AMPs) have been used to cure inflammation and infectious diseases. In this study, we isolated whole housefly larvae insect SVWC peptide 1 (WHIS1), a novel insect single von Willebrand factor C-domain protein (SVWC) peptide from whole housefly larvae. The expression pattern of WHIS1 showed a response to the stimulation of C. albicans. In contrast to other SVWC members, which function as antiviral peptides, interferon (IFN) analogs or pathogen recognition receptors (PRRs), which are the prokaryotically expressed MdWHIS1 protein, inhibit the growth of C. albicans. Eukaryotic heterologous expression of WHIS1 inhibited C. albicans invasion into A549 and HeLa cells. The heterologous expression of WHIS1 clearly inhibited hyphal formation both extracellularly and intracellularly. Furthermore, the mechanism of WHIS1 has demonstrated that it downregulates all key hyphal formation factors (ALS1, ALS3, ALS5, ECE1, HWP1, HGC1, EFG1, and ZAP1) both extracellularly and intracellularly. These data showed that heterologously expressed WHIS1 inhibits C. albicans invasion into epithelial cells by affecting hyphal formation and adhesion factor-related gene expression. These findings provide new potential drug candidates for treating C. albicans infection.

3.
J Environ Manage ; 364: 121311, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38875977

RESUMO

Soil salinization and sodification, the primary causes of land degradation and desertification in arid and semi-arid regions, demand effective monitoring for sustainable land management. This study explores the utility of partial least square (PLS) latent variables (LVs) derived from visible and near-infrared (Vis-NIR) spectroscopy, combined with remote sensing (RS) and auxiliary variables, to predict electrical conductivity (EC) and sodium absorption ratio (SAR) in northern Xinjiang, China. Using 90 soil samples from the Karamay district, machine learning models (Random Forest, Support Vector Regression, Cubist) were tested in four scenarios. Modeling results showed that RS and Land use alone were unreliable predictors, but the addition of topographic attributes significantly improved the prediction accuracy for both EC and SAR. The incorporation of PLS LVs derived from Vis-NIR spectroscopy led to the highest performance by the Random Forest model for EC (CCC = 0.83, R2 = 0.80, nRMSE = 0.48, RPD = 2.12) and SAR (CCC = 0.78, R2 = 0.74, nRMSE = 0.58, RPD = 2.25). The variable importance analysis identified PLS LVs, certain topographic attributes (e.g., valley depth, elevation, channel network base level, diffuse insolation), and specific RS data (i.e., polarization index of VV + VH) as the most influential predictors in the study area. This study affirms the efficiency of Vis-NIR data for digital soil mapping, offering a cost-effective solution. In conclusion, the integration of proximal soil sensing techniques and highly relevant topographic attributes with the RF model has the potential to yield a reliable spatial model for mapping soil EC and SAR. This integrated approach allows for the delineation of hazardous zones, which in turn enables the consideration of best management practices and contributes to the reduction of the risk of degradation in salt-affected and sodicity-affected soils.

4.
Cell Mol Life Sci ; 81(1): 212, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724675

RESUMO

Leydig cells are essential components of testicular interstitial tissue and serve as a primary source of androgen in males. A functional deficiency in Leydig cells often causes severe reproductive disorders; however, the transcriptional programs underlying the fate decisions and steroidogenesis of these cells have not been fully defined. In this study, we report that the homeodomain transcription factor PBX1 is a master regulator of Leydig cell differentiation and testosterone production in mice. PBX1 was highly expressed in Leydig cells and peritubular myoid cells in the adult testis. Conditional deletion of Pbx1 in Leydig cells caused spermatogenic defects and complete sterility. Histological examinations revealed that Pbx1 deletion impaired testicular structure and led to disorganization of the seminiferous tubules. Single-cell RNA-seq analysis revealed that loss of Pbx1 function affected the fate decisions of progenitor Leydig cells and altered the transcription of genes associated with testosterone synthesis in the adult testis. Pbx1 directly regulates the transcription of genes that play important roles in steroidogenesis (Prlr, Nr2f2 and Nedd4). Further analysis demonstrated that deletion of Pbx1 leads to a significant decrease in testosterone levels, accompanied by increases in pregnenolone, androstenedione and luteinizing hormone. Collectively, our data revealed that PBX1 is indispensable for maintaining Leydig cell function. These findings provide insights into testicular dysgenesis and the regulation of hormone secretion in Leydig cells.


Assuntos
Infertilidade Masculina , Células Intersticiais do Testículo , Fator de Transcrição 1 de Leucemia de Células Pré-B , Testículo , Testosterona , Animais , Masculino , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Fator de Transcrição 1 de Leucemia de Células Pré-B/metabolismo , Fator de Transcrição 1 de Leucemia de Células Pré-B/genética , Camundongos , Testosterona/metabolismo , Testículo/metabolismo , Testículo/patologia , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Infertilidade Masculina/metabolismo , Diferenciação Celular/genética , Espermatogênese/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout
5.
J Transl Med ; 22(1): 465, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755664

RESUMO

Disturbance in mitochondrial homeostasis within proximal tubules is a critical characteristic associated with diabetic kidney disease (DKD). CaMKKß/AMPK signaling plays an important role in regulating mitochondrial homeostasis. Despite the downregulation of CaMKKß in DKD pathology, the underlying mechanism remains elusive. The expression of NEDD4L, which is primarily localized to renal proximal tubules, is significantly upregulated in the renal tubules of mice with DKD. Coimmunoprecipitation (Co-IP) assays revealed a physical interaction between NEDD4L and CaMKKß. Moreover, deletion of NEDD4L under high glucose conditions prevented rapid CaMKKß protein degradation. In vitro studies revealed that the aberrant expression of NEDD4L negatively influences the protein stability of CaMKKß. This study also explored the role of NEDD4L in DKD by using AAV-shNedd4L in db/db mice. These findings confirmed that NEDD4L inhibition leads to a decrease in urine protein excretion, tubulointerstitial fibrosis, and oxidative stress, and mitochondrial dysfunction. Further in vitro studies demonstrated that si-Nedd4L suppressed mitochondrial fission and reactive oxygen species (ROS) production, effects antagonized by si-CaMKKß. In summary, the findings provided herein provide strong evidence that dysregulated NEDD4L disturbs mitochondrial homeostasis by negatively modulating CaMKKß in the context of DKD. This evidence underscores the potential of therapeutic interventions targeting NEDD4L and CaMKKß to safeguard renal tubular function in the management of DKD.


Assuntos
Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina , Nefropatias Diabéticas , Regulação para Baixo , Homeostase , Mitocôndrias , Ubiquitina-Proteína Ligases Nedd4 , Animais , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Ubiquitina-Proteína Ligases Nedd4/genética , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Mitocôndrias/metabolismo , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Camundongos Endogâmicos C57BL , Camundongos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Masculino , Estresse Oxidativo , Dinâmica Mitocondrial , Estabilidade Proteica , Proteólise
6.
Arch Dermatol Res ; 316(6): 273, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796649

RESUMO

BACKGROUND: Recent data reveal a marked rise in the detection and mortality rates of Desmoplastic Malignant Melanoma (DMM). This trend underscores the imperative for an in-depth analysis of DMM's epidemiology, which is crucial for the formulation of precise medical and public health strategies. This investigation seeks to elucidate the variations in the incidence and mortality of DMM over a 15-year period (2005-2019). METHODS: Data on DMM patients was sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Both incidence and incidence-based mortality rates (IBM) were directly extracted from the SEER database. Joinpoint regression was used to analyze and calculate the average annual percent change (AAPC) and its 95% confidence interval (CI). RESULTS: Between 2005 and 2019, 3,384 DMM cases were identified, boasting an age-adjusted incidence rate of 36.3 cases per 1000,000 person-years (95% CI 3.51-3.76) and an IBM of 1.65cases per 1000,000 person-years (95% CI 1.57-1.74). Of these, 2,353 were males (69.53%) and 1,031 were females (30.47%). There were 1894 patients (55.97%) who were over 70 years old. Predominantly, DMM lesions manifested in exposed areas: Limbs (955, 28.22%), Face (906, 26.77%), and Scalp and Neck (865, 25.56%). The incidence of DMM increased significantly at a rate of APC = 0.9% during 2005-2019, while the incidence-based mortality showed a significant upward trend (APC = 7%) during 2005-2012, and slowly increasing trend (APC = 0.6%) during 2012-2019. In contrast to the modest upward trajectory in female incidence and mortality, male incidence initially surged, later declining, while male mortality peaked and stabilized post-2012. The primary sites for incidence and mortality were chronically sun-exposed areas: Face, Scalp and Neck, and Limbs. CONCLUSIONS: In recent years, the incidence and incidence-based mortality of DMM have significantly increased. Each subgroup analysis has different trends, and these trends can provide better support for our exploration of DMM.


Assuntos
Melanoma , Programa de SEER , Neoplasias Cutâneas , Humanos , Melanoma/epidemiologia , Melanoma/mortalidade , Melanoma/patologia , Masculino , Feminino , Incidência , Estudos Retrospectivos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Idoso , Pessoa de Meia-Idade , Programa de SEER/estatística & dados numéricos , Adulto , Idoso de 80 Anos ou mais , Estados Unidos/epidemiologia , Adolescente , Adulto Jovem , Análise de Regressão , Criança , Pré-Escolar
7.
Plant Dis ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720538

RESUMO

Soybean (Glycine max) is a significant grain and oil crop. Among the various challenges faced by soybean cultivation, anthracnose stands out as one of the most prevalent diseases. In June 2023, anthracnose symptoms on leaves characterized by irregular disease spots featuring gray-white centers and brown edges, along with many small black dots on their surface, were observed in a 20-hectare soybean (variety "Liu Yuehuang") field located in Luodian County (25°40'20″ N, 106°53'50″ E, 575 m), Guizhou Province, China. Around 30% of the 300 soybean plants examined were symptomatic, and a total of ten leaves were collected. Fragments (5×5 mm) from the edge of disease spots were sheared and surface-sterilized with 3% sodium hypochlorite and 75% ethanol for 60 s and 30 s, respectively. They were then flushed twice with sterile water, dried using sterile filter papers, finally placed on potato dextrose agar (PDA) and incubated at 28°C for two days. In total, 11 isolates with identical morphological characteristics were obtained. The colonies grown with white aerial mycelia on their surface; conidia were cylindrical, both ends are rounded, aseptate, hyaline, 11.0-14.0 (12.5) × 4.5-6.0 (5.0) µm (n = 30); appressoria were nearly ovoid, brown to black, 8.5-10.5 (9.5) × 5.5-7.5 (6.0) µm (n = 30). The morphological characteristics closely resembled the description of C. karstii (Damm et al., 2012). To further identify the isolates, chitin synthase (CHS-1), actin (ACT), beta-tubulin (TUB2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the internal transcribed spacer (ITS) loci were amplified by using CHS-79F/CHS-345R, ACT-512F/ACT-783R (Carbone and Kohn, 1999), Bt2F/Bt2R (Woudenberg et al., 2009), GDF/GDR (Guerber et al., 2003) and ITS1/ITS4 (White et al., 1990) PCR primers, respectively. The BLAST results showed that the sequences of two representative strains, LD 2023048-1 and LD 2023048-2, were highly similar to those of strain C. karstii CGMCC3.14194 (ITS: OR342620 (99%) and OR342621 (99%) with HM585409, ACT: OR412337 (97%) and OR423341 (100%) with HM581995, CHS-1: OR423344 (99%,) and OR423345 (100%) with HM582023, GAPDH: OR423348 (98%) and OR423349 (98%) with HM585391, and TUB: OR423352 (99%) and OR423353 (99%) with HM585428). The phylogenetic tree combined five sequences showed that the two strains clustered into a branch of C. karstii CGMCC3.14194 with high support values. Thirty-day-old soybean plants (n = 10) (variety Liu Yuehuang) were separately sprayed with 1 × 105 spore suspensions/mL of the two strains by spray method, and plants sprayed with sterile distilled water were used as the negative control (n = 5). All the plants were then covered with plastic bags and cultured in the greenhouse (28℃, 80% humidity, 12 h light dark cycle). After ten days of inoculation, plants inoculated with C. karstii began to produce typical anthracnose symptoms, while the control remained asymptomatic. The confirmation of the reisolated pathogen as C. karstii was established through a comprehensive analysis of morphology and five sequencing loci. Pathogenicity tests were repeated three times. Anthracnose on soybean is caused by Colletotrichum spp. reported in China including C. truncatum (Hu et al., 2015), C. brevisporum (Shi et al., 2021) and C. fructicola (Xu et al., 2023). As far as we know, this study is the initial report of C. karstii inducing anthracnose on soybean to date, which establishes a fundamental reference for preventing and controlling this disease.

8.
Emerg Microbes Infect ; 13(1): 2361007, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38801099

RESUMO

Ceftazidime-avibactam resistance attributable to the blaKPC-2 gene mutation is increasingly documented in clinical settings. In this study, we characterized the mechanisms leading to the development of ceftazidime-avibactam resistance in ST11-K47 hypervirulent Klebsiella pneumoniae that harboured the blaKPC-135 gene. This strain possessed fimbriae and biofilm, demonstrating pathogenicity. Compared with the wild-type KPC-2 carbapenemase, the novel KPC-135 enzyme exhibited a deletion of Glu168 and Leu169 and a 15-amino acid tandem repeat between Val262 and Ala276. The blaKPC-135 gene was located within the Tn6296 transposon truncated by IS26 and carried on an IncFII/IncR-type plasmid. Compared to the blaKPC-2-positive cloned strain, only the MIC of ceftazidime increased against blaKPC-135-positive K. pneumoniae and wasn't inhibited by avibactam (MIC 32 µg/mL), while clavulanic acid and vaborbactam demonstrated some inhibition. Kinetic parameters revealed that KPC-135 exhibited a lower Km and kcat/Km with ceftazidime and carbapenems, and a higher (∼26-fold) 50% inhibitory concentration with avibactam compared to KPC-2. The KPC-135 enzyme exerted a detrimental effect on fitness relative to the wild-type strain. Furthermore, this strain possessed hypervirulent determinants, which included the IncHI1B/FIB plasmid with rmpA2 and expression of type 1 and 3 fimbriae. In conclusion, we reported a novel KPC variant, KPC-135, in a clinical ST11-K47 hypervirulent K. pneumoniae strain, which conferred ceftazidime-avibactam resistance, possibly through increased ceftazidime affinity and decreased avibactam susceptibility. This strain simultaneously harboured resistance and virulence genes, posing an elevated challenge in clinical treatment.


Assuntos
Antibacterianos , Compostos Azabicíclicos , Proteínas de Bactérias , Ceftazidima , Combinação de Medicamentos , Infecções por Klebsiella , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , beta-Lactamases , Ceftazidima/farmacologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/patogenicidade , Klebsiella pneumoniae/enzimologia , Compostos Azabicíclicos/farmacologia , Antibacterianos/farmacologia , Infecções por Klebsiella/microbiologia , Infecções por Klebsiella/tratamento farmacológico , beta-Lactamases/genética , beta-Lactamases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Humanos , Virulência , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Farmacorresistência Bacteriana Múltipla/genética , Plasmídeos/genética , Animais
9.
Proteomics Clin Appl ; : e2300106, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639920

RESUMO

BACKGROUND: Cutibacterium acnes is a commensal bacterium residing in healthy skin and plays a critical role in maintaining skin homeostasis. C. acnes has been considered closely related to acne vulgaris, while recent studies suggest that C. acnes and its metabolites may have a protective role in atopic dermatitis (AD) by modulating the immune system and maintaining skin homeostasis. Extracellular vesicles (EVs) are small membranous vesicles secreted by bacteria that participate in bacteria-host interactions. METHODS: This study first compared C. acnes EVs from AD lesions (AD-EVs), acne lesions (Acne-EVs), and healthy skin (NC-EVs), using Label-free quantitative LC-MS/MS and validated differently expressed proteins by parallel reaction monitoring (PRM). Then Normal Human Epidermal Keratinocytes (NHEK) and human primary keratinocytes (KC) were treated with C. acnes EVs isolated from different groups, and the expressions of inflammatory factors were measured by quantitative real-time PCR and Western blotting. RESULTS: Compared with the acne group, the AD group showed greater downregulation of proteins related to energy metabolism and carbon source utilization pathway. Differences in protein profile in AD and acne lesion-separated C. acnes EVs correspond to the abnormal sebum secretion pattern in both diseases. C. acnes EVs from different groups affected different expressions of Th1 and Th2 inflammatory factors and epidermal barrier markers in NHEK and KC, indicating different immunomodulatory potentials. CONCLUSIONS: This study observed distinct proteomic differences between AD-EVs and Acne-EVs, and provided insights into the functional differences of C. acnes EVs in AD and acne.

10.
J Dairy Sci ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38642661

RESUMO

Spermatogenesis is a continuous process in which functional sperm are produced through a series of mitotic and meiotic divisions and morphological changes in germ cells. The aberrant development and fate transitions of spermatogenic cells cause hybrid sterility in mammals. Cattle-yak, a hybrid animal between taurine cattle (Bos taurus) and yak (Bos grunniens), exhibits male-specific sterility due to spermatogenic failure. In the present study, we performed single-cell RNA sequencing analysis to identify differences in testicular cell composition and the developmental trajectory of spermatogenic cells between yak and cattle-yak. The composition and molecular signatures of spermatogonial subtypes were dramatically different between these 2 animals, and the expression of genes associated with stem cell maintenance, cell differentiation and meiotic entry was altered in cattle-yak, indicating the impairment of undifferentiated spermatogonial fate decisions. Cell communication analysis revealed that signaling within different spermatogenic cell subpopulations was weakened, and progenitor spermatogonia were unable or delayed receiving and sending signals for transformation to the next stage in cattle-yak. Simultaneously, the communication between niche cells and germ cells was also abnormal. Collectively, we obtained the expression profiles of transcriptome signatures of different germ cells and testicular somatic cell populations at the single-cell level and identified critical regulators of spermatogonial differentiation and meiosis in yak and sterile cattle-yak. The findings of this study shed light on the genetic mechanisms that lead to hybrid sterility and speciation in bovid species.

11.
Ecol Evol ; 14(4): e11295, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38660471

RESUMO

Among flowering plants, self-incompatibility is considered the most efficient system for avoiding self-fertilization. However, many self-incompatible plants have also evolved floral mechanisms to reduce sexual conflict. In China, some studies of Bulbophyllum have been reported to be self-incompatible and no fruit sets. However, we have observed relatively high fruit sets in Bulbophyllum funingense. Therefore, we speculated that if B. funingense is also self-incompatible, and it might present a floral mechanism to avoid sexual conflict. Natural fruit sets, pollinia removal and deposition rates were determined and breeding system was tested in a hand-pollination experiment. The pollination process and visiting frequency of pollinators and their behavior after escape from access were observed and recorded. Floral traits associated with pollination and pollinator size were measured. B. funingense was completely self-incompatible, the fruit sets of cross-pollination in 2 years were all more than 70%, and the natural fruit sets for 2 years were 1.70 ± 4.31% and 6.63 ± 5.29%, respectively. B. funingense did not produce strong odor or nectar, but produced a kind of secretions from its labellum that attracted flies. Calliphora vicina (Calliphoridae) was its only effective pollinator. When C. vicina licked the secretions, they were stuck in the access for a long time. Thus, when they escaped from access, they almost always flew quickly away from the inflorescence removing pollinia most of the times. In B. funingense, a floral mechanism improves pollinia transfer efficiency, reduces pollinia waste, promotes pollination success, reduces the incidence of self-pollination, and avoids sexual conflict to a certain extent.

12.
BMC Oral Health ; 24(1): 418, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580938

RESUMO

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy. The oncometabolites have been studied in OSCC, but the mechanism of metabolic reprogramming remains unclear. To identify the potential metabolic markers to distinguish malignant oral squamous cell carcinoma (OSCC) tissue from adjacent healthy tissue and study the mechanism of metabolic reprogramming in OSCC. We compared the metabolites between cancerous and paracancerous tissues of OSCC patients by 1HNMR analysis. We established OSCC derived cell lines and analyzed their difference of RNA expression by RNA sequencing. We investigated the metabolism of γ-aminobutyrate in OSCC derived cells by real time PCR and western blotting. Our data revealed that much more γ-aminobutyrate was produced in cancerous tissues of OSCC patients. The investigation based on OSCC derived cells showed that the increase of γ-aminobutyrate was promoted by the synthesis of glutamate beyond the mitochondria. In OSCC cancerous tissue derived cells, the glutamate was catalyzed to glutamine by glutamine synthetase (GLUL), and then the generated glutamine was metabolized to glutamate by glutaminase (GLS). Finally, the glutamate produced by glutamate-glutamine-glutamate cycle was converted to γ-aminobutyrate by glutamate decarboxylase 2 (GAD2). Our study is not only benefit for understanding the pathological mechanisms of OSCC, but also has application prospects for the diagnosis of OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias Bucais/patologia , Glutamina/genética , Glutamina/metabolismo , Reprogramação Metabólica , Glutamatos/genética , Glutamatos/metabolismo , Linhagem Celular Tumoral
13.
J Asian Nat Prod Res ; : 1-9, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602500

RESUMO

Four new tirucallane-type triterpenoids, polystanins H-K (1-4), were obtained from the stems and leaves of Aphanamixis polystachya. Their structures were elucidated by analysis of the spectroscopic data and comparison with literature data. Compounds 1 and 2 showed week inhibitory effects against NO production in LPS-stimulated RAW264.7 cells. All the isolates were investigated for their antifungal activities against drug-resistant Candida albicans.

14.
Cell Signal ; 120: 111187, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38648894

RESUMO

Hypobaric hypoxia, commonly experienced at elevated altitudes, presents significant physiological challenges. Our investigation is centered on the impact of the bromodomain protein 4 (BRD4) under these conditions, especially its interaction with the Wnt/ß-Catenin pathway and resultant effects on glycolytic inflammation and intestinal barrier stability. By combining transcriptome sequencing with bioinformatics, we identified BRD4's key role in hypoxia-related intestinal anomalies. Clinical parameters of altitude sickness patients, including serum BRD4 levels, inflammatory markers, and barrier integrity metrics, were scrutinized. In vitro studies using CCD 841 CoN cells depicted expression changes in BRD4, Interleukin (IL)-1ß, IL-6, and ß-Catenin. Transepithelial electrical resistance (TEER) and FD4 analyses assessed barrier resilience. Hypoxia-induced mouse models, analyzed via H&E staining and Western blot, provided insights into barrier and protein alterations. Under hypoxic conditions, marked BRD4 expression variations emerged. Elevated serum BRD4 in patients coincided with intensified Wnt signaling, inflammation, and barrier deterioration. In vitro, findings showed hypoxia-induced upregulation of BRD4 and inflammatory markers but a decline in Occludin and ZO1, affecting barrier strength-effects mitigated by BRD4 inhibition. Mouse models echoed these patterns, linking BRD4 upregulation in hypoxia to barrier perturbations. Hypobaric hypoxia-induced BRD4 upregulation disrupts the Wnt/ß-Catenin signaling, sparking glycolysis-fueled inflammation and weakening intestinal tight junctions and barrier degradation.


Assuntos
Fatores de Transcrição , Via de Sinalização Wnt , Humanos , Animais , Fatores de Transcrição/metabolismo , Camundongos , Masculino , Mucosa Intestinal/metabolismo , Doença da Altitude/metabolismo , Proteínas de Ciclo Celular/metabolismo , Camundongos Endogâmicos C57BL , Hipóxia/metabolismo , beta Catenina/metabolismo , Feminino , Inflamação/metabolismo , Adulto , Proteínas que Contêm Bromodomínio
15.
J Int Med Res ; 52(4): 3000605241244756, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38661095

RESUMO

Pylephlebitis, which is a type of septic thrombophlebitis of the portal vein, is a rare and life-threatening complication that commonly occurs following appendicitis. However, nonspecific abdominal complaints and fever can impede the diagnosis of pylephlebitis. Timely use of appropriate antibiotics and anticoagulants is paramount for treating this condition. We present a case of pylephlebitis and septic shock caused by acute nonperforated appendicitis. A 32-year-old man presented with migratory right lower abdominal pain. Blood cultures showed the presence of Escherichia coli. Blood test results showed increased bilirubin concentrations and coagulation factor abnormalities. A computed tomographic abdominal scan showed that the portal vein had a widened intrinsic diameter. After intensive care treatment with antibiotics, antishock therapy, anticoagulants, and other supportive treatments, the infection was monitored, the abdominal pain disappeared, and the jaundice subsided. Laparoscopic appendectomy was performed. Histopathology showed acute suppurative appendicitis, and no abnormalities were observed during the follow-up period after discharge. A multidisciplinary approach is mandatory for the decision-making process in the presence of pylephlebitis caused by appendicitis to obtain a correct diagnosis and prompt treatment. Similarly, the timing of appendectomy is important for minimizing intra- and postoperative complications.


Assuntos
Apendicite , Veia Porta , Choque Séptico , Tromboflebite , Humanos , Apendicite/complicações , Apendicite/cirurgia , Apendicite/diagnóstico , Masculino , Adulto , Tromboflebite/diagnóstico , Tromboflebite/etiologia , Tromboflebite/microbiologia , Choque Séptico/etiologia , Choque Séptico/microbiologia , Veia Porta/patologia , Antibacterianos/uso terapêutico , Apendicectomia , Tomografia Computadorizada por Raios X , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/diagnóstico , Doença Aguda , Dor Abdominal/etiologia
16.
Sci Bull (Beijing) ; 69(11): 1653-1659, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38641514

RESUMO

Topological band theory has conventionally been concerned with the topology of bands around a single gap. Only recently non-Abelian topologies that thrive on involving multiple gaps were studied, unveiling a new horizon in topological physics beyond the conventional paradigm. Here, we report on the first experimental realization of a topological Euler insulator phase with unique meronic characterization in an acoustic metamaterial. We demonstrate that this topological phase has several nontrivial features: First, the system cannot be described by conventional topological band theory, but has a nontrivial Euler class that captures the unconventional geometry of the Bloch bands in the Brillouin zone. Second, we uncover in theory and probe in experiments a meronic configuration of the bulk Bloch states for the first time. Third, using a detailed symmetry analysis, we show that the topological Euler insulator evolves from a non-Abelian topological semimetal phase via. the annihilation of Dirac points in pairs in one of the band gaps. With these nontrivial properties, we establish concretely an unconventional bulk-edge correspondence which is confirmed by directly measuring the edge states via. pump-probe techniques. Our work thus unveils a nontrivial topological Euler insulator phase with a unique meronic pattern and paves the way as a platform for non-Abelian topological phenomena.

17.
Zookeys ; 1193: 145-160, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487668

RESUMO

The genus Svistella Gorochov, 1987 includes 10 species from Asia, with nine documented in China. In this study, a new species, Svistellayayun He, sp. nov., is described from Xizang, China. Morphologically, it resembles S.rufonotata (Chopard, 1932) but can be distinguished by a smaller inner tympanum, dark-brown setae on the 5th segment of the maxillary palp, and a rounded apex on the ectoparamere. To validate our morphological inferences and support the description of S.yayunsp. nov. as a new species, we performed a PCA based on bioacoustics parameters and molecular analysis. All Svistella species documented in China are distinguished by integrating their songs and DNA barcoding.

18.
Crit Rev Food Sci Nutr ; : 1-15, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441497

RESUMO

The cold chain is an integral part of the modern food industry. Low temperatures can effectively alleviate food loss and the transmission of foodborne diseases caused by microbial reproduction. However, recent reports have highlighted shortcomings in the current cold chain technology's ability to prevent and control cold-tolerant foodborne pathogens. Furthermore, it has been observed that certain cold-chain foods have emerged as new sources of infection for foodborne disease outbreaks. Consequently, there is a pressing need to enhance control measures targeting cold-tolerant pathogens within the existing cold chain system. This paper aims to review the recent advancements in understanding the cold tolerance mechanisms of key model organisms, identify key issues in current research, and explore the potential of utilizing big data and omics technology in future studies.

19.
JACC Basic Transl Sci ; 9(2): 203-219, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38510716

RESUMO

The epicardium provides epicardial-derived cells and molecular signals to support cardiac development and regeneration. Zebrafish and mouse studies have shown that ccm2, a cerebral cavernous malformation disease gene, is essential for cardiac development. Endocardial cell-specific deletion of Ccm2 in mice has previously established that Ccm2 is essential for maintenance of the cardiac jelly for cardiac development during early gestation. The current study aimed to explore the function of Ccm2 in epicardial cells for heart development and regeneration. Through genetic deletion of Ccm2 in epicardial cells, our in vivo and ex vivo experiments revealed that Ccm2 is required by epicardial cells to support heart development. Ccm2 regulates epicardial cell adhesion, cell polarity, cell spreading, and migration. Importantly, the loss of Ccm2 in epicardial cells delays cardiac function recovery and aggravates cardiac fibrosis following myocardial infarction. Molecularly, Ccm2 targets the production of cytoskeletal and matrix proteins to maintain epicardial cell function and behaviors. Epicardial Ccm2 plays a critical role in heart development and regeneration via its regulation of cytoskeleton reorganization.

20.
J Med Virol ; 96(3): e29487, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38482901

RESUMO

Human norovirus (HuNoV) is the most predominant viral agents of acute gastroenteritis. Point-of-care testing (POCT) based on lateral flow immunochromatography (LIFC) has become an important tool for rapid diagnosis of HuNoVs. However, low sensitivity and lack of quantitation are the bottlenecks of traditional LIFC. Thus, we established a rapid and accurate technique that combined immunomagnetic enrichment (IM) with LFIC to identify GII HuNoVs in fecal specimens. Before preparing immunofluorescent nanomagnetic microspheres and achieving the effect of HuNoV enrichment in IM and fluorescent signal in LFIC, amino-functionalized magnetic beads (MBs) and carboxylated quantum dots (QDs) were coupled at a mass ratio of 4:10. Anti-HuNoV monoclonal antibody was then conjugated with QDs-MB. The limit of detection was 1.56 × 104 copies/mL, and the quantitative detection range was 1.56 × 104 copies/mL-1 × 106 copies/mL under optimal circumstances. The common HuNoV genotypes GII.2, GII.3, GII.4, and GII.17 can be detected, there was no cross-reaction with various enteric viruses, including rotavirus, astrovirus, enterovirus, and sapovirus. A comparison between IM-LFIC and RT-qPCR for the detection of 87 fecal specimens showed a high level of agreement (kappa = 0.799). This suggested that the method is rapid and sensitive, making it a promising option for point-of-care testing in the future.


Assuntos
Infecções por Caliciviridae , Gastroenterite , Norovirus , Rotavirus , Sapovirus , Humanos , Norovirus/genética , Microesferas , Rotavirus/genética , Sapovirus/genética , Fezes , Infecções por Caliciviridae/diagnóstico
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