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Transporting epithelial cells build apical microvilli to increase membrane surface area and enhance absorptive capacity. The intestinal brush border provides an elaborate example with tightly packed microvilli that function in nutrient absorption and host defense. Although the brush border is essential for physiological homeostasis, its assembly is poorly understood. We found that brush border assembly is driven by the formation of Ca(2+)-dependent adhesion links between adjacent microvilli. Intermicrovillar links are composed of protocadherin-24 and mucin-like protocadherin, which target to microvillar tips and interact to form a trans-heterophilic complex. The cytoplasmic domains of microvillar protocadherins interact with the scaffolding protein, harmonin, and myosin-7b, which promote localization to microvillar tips. Finally, a mouse model of Usher syndrome lacking harmonin exhibits microvillar protocadherin mislocalization and severe defects in brush border morphology. These data reveal an adhesion-based mechanism for brush border assembly and illuminate the basis of intestinal pathology in patients with Usher syndrome. PAPERFLICK:
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Caderinas/metabolismo , Enterócitos/metabolismo , Microvilosidades/metabolismo , Animais , Células COS , Células CACO-2 , Proteínas Relacionadas a Caderinas , Cálcio/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular , Chlorocebus aethiops , Proteínas do Citoesqueleto , Modelos Animais de Doenças , Enterócitos/citologia , Células HEK293 , Humanos , Camundongos , Camundongos Knockout , Microvilosidades/ultraestrutura , Miosinas/metabolismo , Síndromes de Usher/patologiaRESUMO
Plants undergo translational reprogramming when they are under attack by pathogens. Xiang et al. recently revealed that plant helicases induced by pathogen recognition unwind RNA hairpins upstream of the main open reading frames (mORFs), thus allowing ribosomes to bypass the upstream ORFs (uORFs) and translate downstream defense proteins, a mechanism that is also found in mammals.
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Proteínas de Plantas , Biossíntese de Proteínas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ribossomos/metabolismo , RNA/metabolismo , DNA Helicases/metabolismo , Fases de Leitura AbertaRESUMO
The plant hormone salicylic acid (SA) receptor NONEXPRESSOR OF PATHOGENESIS-RELATED PROTEINS1 (NPR1) plays a critical role for plant defense against biotrophic and hemi-biotrophic pathogens. In a milestone paper, Kumar, Zavaliev, Wu et al. unraveled the structural basis for the assembly of an enhanceosome by NPR1 in activating the expression of plant defense genes.
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Proteínas de Arabidopsis , Arabidopsis , Animais , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Aves/metabolismo , Plantas/metabolismo , Ácido Salicílico/metabolismoRESUMO
Staphylococcus aureus expresses three high-affinity neutrophil serine protease (NSP) inhibitors known as the extracellular adherence protein domain (EAPs) proteins. Whereas EapH1 and EapH2 are comprised of a single EAP domain, the modular extracellular adherence protein (Eap) from S. aureus strain Mu50 consists of four EAP domains. We recently reported that EapH2 can simultaneously bind and inhibit cathepsin-G (CG) and neutrophil elastase (NE), which are the two most abundant NSPs. This unusual property of EapH2 arises from independent CG and NE-binding sites that lie on opposing faces of its EAP domain. Here we used X-ray crystallography and enzyme assays to show that all four individual domains of Eap (i.e. Eap1, Eap2, Eap3, and Eap4) exhibit an EapH2-like ability to form ternary complexes with CG and NE that inhibit both enzymes simultaneously. We found that Eap1, Eap2, and Eap3 have similar functional profiles insofar as NSP inhibition is concerned, but that Eap4 displays an unexpected ability to inhibit two NE enzymes simultaneously. Using X-ray crystallography, we determined that this second NE-binding site in Eap4 arises through the same region of its EAP domain that also comprises its CG-binding site. Interestingly, small angle X-ray scattering data showed that stable tail-to-tail dimers of the NE/Eap4/NE ternary complex exist in solution. This arrangement is compatible with NSP-binding at all available sites in a two-domain fragment of Eap. Together, our work implies that Eap is a polyvalent inhibitor of NSPs. It also raises the possibility that higher-order structures of NSP-bound Eap may have unique functional properties.
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BACKGROUND: Tuberculosis (TB), predominantly caused by Mycobacterium tuberculosis (MTB) infection, remains a prominent global health challenge. Macrophages are the frontline defense against MTB, relying on autophagy for intracellular bacterial clearance. However, MTB can combat and evade autophagy, and it influences macrophage polarization, facilitating immune evasion and promoting infection. We previously found that heparin-binding hemagglutinin (HBHA) inhibits autophagy in A549 cells; however, its role in macrophage autophagy and polarization remains unclear. METHODS: Bacterial cultures, cell cultures, Western blotting, immunofluorescence, macrophage infection assays, siRNA knockdown, and enzyme-linked immunosorbent assay were used to investigate HBHA's impact on macrophages and its relevance in Mycobacterium infection. RESULTS: HBHA inhibited macrophage autophagy. Expression of recombinant HBHA in Mycobacterium smegmatis (rMS-HBHA) inhibited autophagy, promoting bacterial survival within macrophages. Conversely, HBHA knockout in the Mycobacterium bovis bacillus Calmette-Guérin (BCG) mutant (BCG-ΔHBHA) activated autophagy and reduced bacterial survival. Mechanistic investigations revealed that HBHA may inhibit macrophage autophagy through the Toll-like receptor 4-dependent PI3K-AKT-mTOR signaling pathway. Furthermore, HBHA induced macrophage M2 polarization. CONCLUSIONS: Mycobacterium may exploit HBHA to suppress the antimicrobial immune response in macrophages, facilitating intracellular survival and immune evasion through autophagy inhibition and M2 polarization induction. Our findings may help identify novel therapeutic targets and develop more effective treatments against MTB infection.
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Autofagia , Macrófagos , Mycobacterium tuberculosis , Receptor 4 Toll-Like , Macrófagos/imunologia , Macrófagos/microbiologia , Macrófagos/metabolismo , Mycobacterium tuberculosis/imunologia , Humanos , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/genética , Transdução de Sinais , Animais , Mycobacterium smegmatis/imunologia , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/metabolismo , Tuberculose/imunologia , Tuberculose/microbiologia , Lectinas/metabolismo , Lectinas/genética , Camundongos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Evasão da Resposta Imune , Mycobacterium bovis/imunologia , Células A549 , Serina-Treonina Quinases TOR/metabolismoRESUMO
There is growing acknowledgment that the properties of the electrochemical interfaces play an increasingly pivotal role in improving the performance of the hydrogen evolution reaction (HER). Here, we present, for the first time, direct dynamic spectral evidence illustrating the impact of the interaction between interfacial water molecules and adsorbed hydroxyl species (OHad) on the HER properties of Ni(OH)2 using Au/core-Ni(OH)2/shell nanoparticle-enhanced Raman spectroscopy. Notably, our findings highlight that the interaction between OHad and interfacial water molecules promotes the formation of weakly hydrogen-bonded water, fostering an environment conducive to improving the HER performance. Furthermore, the participation of OHad in the reaction is substantiated by the observed deprotonation step of Au@2 nm Ni(OH)2 during the HER process. This phenomenon is corroborated by the phase transition of Ni(OH)2 to NiO, as verified through Raman and X-ray photoelectron spectroscopy. The significant redshift in the OH-stretching frequency of water molecules during the phase transition confirms that surface OHad disrupts the hydrogen-bond network of interfacial water molecules. Through manipulation of the shell thickness of Au@Ni(OH)2, we additionally validate the interaction between OHad and interfacial water molecules. In summary, our insights emphasize the potential of electrochemical interfacial engineering as a potent approach to enhance electrocatalytic performance.
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BACKGROUND & AIMS: HBV expresses more than 10 spliced RNAs from the viral pregenomic RNA, but their functions remain elusive and controversial. To address the function of HBV spliced RNAs, we generated splicing-deficient HBV mutants and conducted experiments to assess the impact of these mutants on HBV infection. METHODS: HepG2-NTCP cells, human hepatocyte chimeric FRG mice (hu-FRG mice), and serum from patients with chronic hepatitis B were used for experiments on HBV infection. Additionally, SHifter assays and cryo-electron microscopy were performed. RESULTS: We found the infectivity of splicing-deficient HBV was decreased 100-1,000-fold compared with that of wild-type HBV in hu-FRG mice. Another mutant, A487C, which loses the most abundant spliced RNA (SP1), also exhibits severely impaired infectivity. SP1 hypothetically encodes a novel protein HBcSP1 (HBc-Cys) that lacks the C-terminal cysteine from full-length HBc. In the SHifter assay, HBcSP1 was detected in wild-type viral particles at a ratio of about 20-100% vs. conventional HBc, as well as in the serum of patients with chronic hepatitis B, but not in A487C particles. When infection was conducted with a shorter incubation time of 4-8 h at lower PEG concentrations in HepG2-NTCP cells, the entry of the A487C mutant was significantly slower. SP1 cDNA complementation of the A487C mutant succeeded in rescuing its infectivity in hu-FRG mice and HepG2-NTCP cells. Moreover, cryo-electron microscopy revealed a disulfide bond between HBc cysteine 183 and 48 in the HBc intradimer of the A487C capsid, leading to a locked conformation that disfavored viral entry in contrast to the wild-type capsid. CONCLUSIONS: Prior studies unveiled the potential integration of the HBc-Cys protein into the HBV capsid. We confirmed the proposal and validated its identity and function during infection. IMPACT AND IMPLICATIONS: HBV SP1 RNA encodes a novel HBc protein (HBcSP1) that lacks the C-terminal cysteine from conventional HBc (HBc-Cys). HBcSP1 was detected in cell culture-derived HBV and confirmed in patients with chronic infection by both immunological and chemical modification assays at 10-50% of capsid. The splicing-deficient mutant HBV (A487C) impaired infectivity in human hepatocyte chimeric mice and viral entry in the HepG2-NTCP cell line. Furthermore, these deficiencies of the splicing-deficient mutant could be rescued by complementation with the SP1-encoded protein HBcSP1. We confirmed and validated the identity and function of HBcSP1 during infection, building on the current model of HBV particles.
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Vírus da Hepatite B , Hepatite B Crônica , Humanos , Animais , Vírus da Hepatite B/genética , Camundongos , Células Hep G2 , Hepatite B Crônica/virologia , Splicing de RNA , Mutação , RNA Viral/genética , RNA Viral/metabolismo , Microscopia CrioeletrônicaRESUMO
Surface-enhanced Raman scattering (SERS) can overcome the existing technological limitations, such as complex processes and harsh conditions in gaseous small-molecule detection, and advance the development of real-time gas sensing at room temperature. In this study, a SERS-based hydrogen bonding induction strategy for capturing and sensing gaseous acetic acid is proposed for the detection demands of gaseous acetic acid. This addresses the challenges of low adsorption of gaseous small molecules on SERS substrates and small Raman scattering cross sections and enables the first SERS-based detection of gaseous acetic acid by a portable Raman spectrometer. To provide abundant hydrogen bond donors and acceptors, 4-mercaptobenzoic acid (4-MBA) was used as a ligand molecule modified on the SERS substrate. Furthermore, a sensing chip with a low relative standard deviation (RSD) of 4.15% was constructed, ensuring highly sensitive and reliable detection. The hydrogen bond-induced acetic acid trapping was confirmed by experimental spectroscopy and density functional theory (DFT). In addition, to achieve superior accuracy compared to conventional methods, an innovative analytical method based on direct response hydrogen bond formation (IO-H/Iref) was proposed, enabling the detection of gaseous acetic acid at concentrations as low as 60 ppb. The strategy demonstrated a superior anti-interference capability in simulated breath and wine detection systems. Moreover, the high reusability of the chip highlights the significant potential for real-time sensing of gaseous acetic acid.
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Hepatitis B virus (HBV) is a major cause of liver cirrhosis and hepatocellular carcinoma, with HBV surface antigen (HBsAg) being a crucial marker in the clinical detection of HBV. Due to the significant harm and ease of transmission associated with HBV, HBsAg testing has become an essential part of preoperative assessments, particularly for emergency surgeries where healthcare professionals face exposure risks. Therefore, a timely and accurate detection method for HBsAg is urgently needed. In this study, a surface-enhanced Raman scattering (SERS) sensor with a sandwich structure was developed for HBsAg detection. Leveraging the ultrasensitive and rapid detection capabilities of SERS, this sensor enables quick detection results, significantly reducing waiting times. By systematically optimizing critical factors in the detection process, such as the composition and concentration of the incubation solution as well as the modification conditions and amount of probe particles, the sensitivity of the SERS immune assay system was improved. Ultimately, the sensor achieved a sensitivity of 0.00576 IU/mL within 12 min, surpassing the clinical requirement of 0.05 IU/mL by an order of magnitude. In clinical serum assay validation, the issue of false positives was effectively addressed by adding a blocker. The final sensor demonstrated 100% specificity and sensitivity at the threshold of 0.05 IU/mL. Therefore, this study not only designed an ultrasensitive SERS sensor for detecting HBsAg in actual clinical serum samples but also provided theoretical support for similar systems, filling the knowledge gap in existing literature.
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Antígenos de Superfície da Hepatite B , Análise Espectral Raman , Antígenos de Superfície da Hepatite B/sangue , Análise Espectral Raman/métodos , Humanos , Vírus da Hepatite B/isolamento & purificação , Nanopartículas Metálicas/química , Hepatite B/sangue , Hepatite B/diagnóstico , Propriedades de Superfície , Limite de DetecçãoRESUMO
BACKGROUND: The tumor microenvironment (TME) encompasses a variety of cells that influence immune responses and tumor growth, with tumor-associated macrophages (TAM) being a crucial component of the TME. TAM can guide prostate cancer in different directions in response to various external stimuli. METHODS: First, we downloaded prostate cancer single-cell sequencing data and second-generation sequencing data from multiple public databases. From these data, we identified characteristic genes associated with TAM clusters. We then employed machine learning techniques to select the most accurate TAM gene set and developed a TAM-related risk label for prostate cancer. We analyzed the tumor-relatedness of the TAM-related risk label and different risk groups within the population. Finally, we validated the accuracy of the prognostic label using single-cell sequencing data, qPCR, and WB assays, among other methods. RESULTS: In this study, the TAM_2 cell cluster has been identified as promoting the progression of prostate cancer, possibly representing M2 macrophages. The 9 TAM feature genes selected through ten machine learning methods and demonstrated their effectiveness in predicting the progression of prostate cancer patients. Additionally, we have linked these TAM feature genes to clinical pathological characteristics, allowing us to construct a nomogram. This nomogram provides clinical practitioners with a quantitative tool for assessing the prognosis of prostate cancer patients. CONCLUSION: This study has analyzed the potential relationship between TAM and PCa and established a TAM-related prognostic model. It holds promise as a valuable tool for the management and treatment of PCa patients.
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Macrófagos , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/genética , Macrófagos Associados a Tumor , Aprendizado de Máquina , Nomogramas , Microambiente Tumoral/genéticaRESUMO
Parkinson's disease (PD) is currently the second most incurable central neurodegenerative disease resulting from various pathogenesis. As the "energy factory" of cells, mitochondria play an extremely important role in supporting neuronal signal transmission and other physiological activities. Mitochondrial dysfunction can cause and accelerate the occurrence and progression of PD. How to effectively prevent and suppress mitochondrial disorders is a key strategy for the treatment of PD from the root. Therefore, the emerging mitochondria-targeted therapy has attracted considerable interest. Herein, the relationship between mitochondrial dysfunction and PD, the causes and results of mitochondrial dysfunction, and major strategies for ameliorating mitochondrial dysfunction to treat PD are systematically reviewed. The study also prospects the main challenges for the treatment of PD.
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Mitocôndrias , Doença de Parkinson , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , AnimaisRESUMO
BACKGROUND: This study was designed to develop an innovative classification and guidance system for renal hilar tumors and to assess the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) for managing such tumors. METHODS: A total of 179 patients undergoing RAPN for renal hilar tumors were retrospectively reviewed. A novel classification system with surgical techniques was introduced and the perioperative features, tumor characteristics, and the efficacy and safety of RAPN were compared within subgroups. RESULTS: We classified the tumors according to our novel system as follows: 131 Type I, 35 Type II, and 13 Type III. However, Type III had higher median R.E.N.A.L., PADUA, and ROADS scores compared with the others (all p < 0.001), indicating increased operative complexity and higher estimated blood loss [180.00 (115.00-215.00) ml]. Operative outcomes revealed significant disparities between Type III and the others, with longer operative times [165.00 (145.00-200.50) min], warm ischemia times [24.00 (21.50-30.50) min], tumor resection times [13.00 (12.00-15.50) min], and incision closure times [22.00 (20.00-23.50) min] (all p < 0.005). Postoperative outcomes also showed significant differences, with longer durations of drain removal (77.08 ± 18.16 h) and hospitalization for Type III [5.00 (5.00-6.00) d] (all p < 0.05). Additionally, Type I had a larger tumor diameter than the others (p = 0.009) and pT stage differed significantly between the subtypes (p = 0.020). CONCLUSIONS: The novel renal hilar tumor classification system is capable of differentiating the surgical difficulty of RAPN and further offers personalized surgical steps tailored to each specific classification. It provides a meaningful tool for clinical practice.
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Neoplasias Renais , Nefrectomia , Procedimentos Cirúrgicos Robóticos , Humanos , Neoplasias Renais/cirurgia , Neoplasias Renais/classificação , Neoplasias Renais/patologia , Feminino , Masculino , Nefrectomia/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/métodos , Seguimentos , Idoso , Duração da Cirurgia , Prognóstico , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/etiologia , Tempo de Internação/estatística & dados numéricos , Adulto , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/classificação , Isquemia Quente , Perda Sanguínea Cirúrgica/estatística & dados numéricosRESUMO
Lipotoxicity caused by excess free fatty acids, particularly saturated fatty acids (SFAs) such as palmitic acid (PA), is one of the most important pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, unsaturated fatty acids (UFAs), such as oleic acid (OA), are nontoxic and can combat SFA-induced toxicity through alleviation of cell apoptosis, endoplasmic reticulum stress (ER stress) and lipids metabolism disorder. However, whether OA is able to regulate autophagy is largely unknown. So, this study aims to investigate the mechanism underlying OA mediated modulation of autophagy in hepatocytes and mice with NAFLD. In vitro, human hepatoma cell line HepG2 cells, human normal liver cells L-02 and mouse normal liver cells AML12 were treated with palmitic acid (PA)/tunicamycin (TM) or/and OA for 48 h. In vivo, C57/BL6 mice were fed with high fat diet (HFD) to induce NAFLD. And the HFD was partial replaced by olive oil to observe the protective effects of olive oil. We demonstrated that PA/TM impaired cell viability and induced cellular apoptosis in HepG2 cells and L-02 cells. Moreover, PA/TM induced autophagy impairment by reducing the nuclear translocation of transcription factor EB (TFEB) and inhibiting the activity of CTSB. However, OA substantially alleviated PA/TM induced cellular apoptosis and autophagy dysfunction in hepatocytes. Additionally, restoring autophagy function is able to reduce ER stress. Similarly, HFD for 20 weeks successfully established NAFLD model in C57/BL6 mice, and significant autophagy impairment were observed in liver tissues. Noteworthily, 30% replacement of HFD with olive oil had profoundly reversed NAFLD. It significantly impoved steatosis, and reduced autophagy dysfunction, ER stress and apoptosis in liver tissue. Conclusively, these data demonstrated that OA is able to effectively impove autophagy dysfunction under the context of both PA and ER stress inducer induced lipotoxicity, and OA mediated regulation of lysosome dysfunction through TFEB plays an important role, suggesting that the regulation of ER stress-autophagy axis is a critical mechanism in OA driven protection in NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Camundongos , Humanos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácido Oleico/farmacologia , Ácido Oleico/metabolismo , Azeite de Oliva/metabolismo , Azeite de Oliva/farmacologia , Fígado/metabolismo , Hepatócitos/metabolismo , Ácido Palmítico/farmacologia , Autofagia , Estresse do Retículo Endoplasmático , Dieta Hiperlipídica/efeitos adversosRESUMO
Electrocatalytic CO2 reduction reaction (CO2RR) for CH4 production presents a promising strategy to address carbon neutrality, and the incorporation of a second metal has been proven effective in enhancing catalyst performance. Nevertheless, there remains limited comprehension regarding the fundamental factors responsible for the improved performance. Herein, the critical role of Pd in electrocatalytic CO2 reduction to CH4 on Cu-based catalysts has been revealed at a molecular level using in situ surface-enhanced Raman spectroscopy (SERS). A "borrowing" SERS strategy has been developed by depositing Cu-Pd overlayers on plasmonic Au nanoparticles to achieve the in situ monitoring of the dynamic change of the intermediate during CO2RR. Electrochemical tests demonstrate that Pd incorporation significantly enhances selectivity toward CH4 production, and the Faradaic efficiency (FE) of CH4 is more than two times higher than that for the catalysts without Pd. The key intermediates, including *CO2-, *CO, and *OH, have been directly identified under CO2RR conditions, and their evolution with the electrochemical environments has been determined. It is found that Pd incorporation promotes the activation of both CO2 and H2O molecules and accelerates the formation of abundant active *CO and hydrogen species, thus enhancing the CH4 selectivity. This work offers fundamental insights into the understanding of the molecular mechanism of CO2RR and opens up possibilities for designing more efficient electrocatalysts.
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This study aims to identify lactic acid bacteria (LAB) isolates possessing physiological characteristics suitable for use as probiotics in yogurt fermentation. Following acid and bile salt tolerance tests, Lactiplantibacillus plantarum (NUC08 and NUC101), Lacticaseibacillus rhamnosus (NUC55 and NUC201), and Lacticaseibacillus paracasei (NUC159, NUC216, and NUC351) were shortlisted based on intraspecies distribution for further evaluation. Their physiological probiotic properties, including transit tolerance, adhesion, autoaggregation, surface hydrophobicity, biofilm formation, and antibacterial activity, were assessed. Principal component analysis indicated that Lactiplantibacillus plantarum NUC08 was the preferred choice among the evaluated strains. Subsequent investigations revealed that co-culturing Lactiplantibacillus plantarum NUC08 with 2 yogurt starter strains resulted in a cooperative and synergistic effect, enhancing the growth of mixed strains and increasing their tolerance to simulated gastric and intestinal conditions. Additionally, when Vibrio harveyi bioluminescent reporter strain was used, the 3 cocultured strains cooperated to induce the activity of a quorum sensing (QS) molecule autoinducer-2 (AI-2), hinting a potential connection between phenotypic traits and QS in the cocultured strains. Importantly, LAB viable counts were significantly higher in yogurt co-fermented with Lactiplantibacillus plantarum NUC08, consistently throughout the storage period. In conclusion, the study demonstrates that the probiotic strain Lactiplantibacillus plantarum NUC08 can be employed in synergy with yogurt starter strains, affirming its potential for use in the development of functional fermented dairy products.
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Produtos Fermentados do Leite , Lactobacillus plantarum , Probióticos , Animais , Iogurte/microbiologia , Lactobacillus plantarum/fisiologia , LactobacillaceaeRESUMO
OBJECTIVE: To identify tumor-associated macrophages (TAMs) related molecular subtypes and develop a TAMs related prognostic model for prostate cancer (PCa). METHODS: Consensus clustering analysis was used to identify TAMs related molecular clusters. A TAMs related prognostic model was developed using univariate and multivariate Cox analysis. RESULTS: Three TAMs related molecular clusters were identified and were confirmed to be associated with prognosis, clinicopathological characteristics, PD-L1 expression levels and tumor microenvironment. A TAMs related prognostic model was constructed. Patients in low-risk group all showed a more appreciable biochemical recurrence-free survival (BCRFS) than patients in high-risk group in train cohort, test cohort, entire TCGA cohort and validation cohort. SLC26A3 attenuated progression of PCa and prevented macrophage polarizing to TAMs phenotype, which was initially verified. CONCLUSIONS: We successfully identified molecular clusters related to TAMs. Additionally, we developed a prognostic model involving TAMs that exhibits excellent predictive performance for biochemical recurrence-free survival in PCa.
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Neoplasias da Próstata , Macrófagos Associados a Tumor , Masculino , Humanos , Prognóstico , Neoplasias da Próstata/metabolismo , Macrófagos , Fenótipo , Microambiente TumoralRESUMO
BACKGROUND AND OBJECTIVES: To systematically investigate the association between the dietary inflammatory index (DII) and gestational diabetes mellitus (GDM), with a focus on the role of BMI in this relationship. METHODS AND STUDY DESIGN: A comprehensive search was conducted in PubMed, Embase, Web of Science, The Cochrane Library, Medline, CINAHL Complete, Chinese Periodical Full-text Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Wanfang Database for rele-vant observational studies published up to August 2023. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. The pooled effect size was calculated using a random-effects model. Sub-group and meta-regression analyses were performed to explore potential sources of heterogeneity. RESULTS: The study included 54,058 participants from 10 studies. Pregnant women with a higher DII, indicating a pro-inflammatory diet, had a significantly increased risk of GDM compared to those with a lower DII, indicating an anti-inflammatory diet (pooled OR: 1.17, 95% CI: 1.01-1.36; I²=70%, p <0.001). Subgroup analyses revealed a stronger association in normal weight stratification (OR: 1.25, 95%CI: 1.04-1.51), case-control studies (OR: 1.45, 95%CI: 1.03-2.05), Asia (OR: 1.26, 95%CI: 1.10-1.43), Europe (OR: 1.27, 95%CI: 1.09-1.48), 3-day dietary record as a dietary assessment tool (OR: 1.30, 95%CI: 1.16-1.46), physical activity adjustment (OR: 1.28, 95%CI: 1.13-1.46), and energy intake adjustment (OR: 1.33, 95%CI: 1.19-1.48). Meta-regression analysis confirmed that geographical region significantly influenced heterogeneity between studies (p <0.05). CONCLUSIONS: An elevated DII is independently linked to a higher risk of GDM, especially in women of normal weight.
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Diabetes Gestacional , Dieta , Inflamação , Sobrepeso , Humanos , Diabetes Gestacional/epidemiologia , Feminino , Gravidez , Dieta/métodos , Estudos Observacionais como AssuntoRESUMO
We aimed to analyze the effects of exclusive breastfeeding duration on the occurrence and course of pneumonia in infants aged up to 6 months. Prospective case-control study. This study was conducted from August 2020 to August 2022 at a maternity and child health hospital in China. A total of 218 infants up to 6 months of age with pneumonia were included in the analyses. Health data were obtained using a hospitalization information system or an interview-based questionnaire. Univariate and multivariate logistic regression analyses were performed to analyze the data. The incidence of pneumonia, hospitalization duration, and costs to participants were significantly affected by the duration of exclusive breastfeeding (p < 0.01). The incidence of pneumonia among participants with different exclusive breastfeeding durations also differed significantly (p < 0.01). The shorter the duration of exclusive breastfeeding, the higher the incidence of pneumonia among infants. We found that the longer the exclusive breastfeeding duration in infants up to 6 months of age, the lower the recurrence of pneumonia, the shorter the hospital stay, and the lower the hospital costs. The rate of exclusive breastfeeding for infants up to 6 months of age should be increased as much as possible to reduce the occurrence of pneumonia and hospital costs.
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OBJECTIVE: To investigate the current situation of sitting time and health literacy among high school students in China, in order to provide a basis for improving their physical and mental health levels. METHODS: A stratified random cluster sampling method was used to investigate the length of sitting time and health literacy of first and second grade high school students from 31 provinces, cities, and autonomous regions in China(data did not include that of Hong Kong and Macao Special Administrative Region, and Taiwan Province of China). The Kruskal-Wallis H method, independent sample Mann-Whitney U test, and regression model were used to analyze the influencing factors of sitting time and total health literacy score. RESULTS: (1) The total score of health literacy was statistically significant (P < 0.01) in different regions, urban and rural distribution, annual family income, parents' educational background, age, and gender. (2) The length of sitting was statistically significant (P < 0.01) among multiple groups in different regions, family annual income, parental education, and gender. However, there was no statistically significant difference between groups of different ages and urban-rural distribution (P>0.05). (3) The analysis of multiple linear regression model showed that the total score of health literacy was positively correlated with the family' s annual income and the mother' s education, and negatively correlated with the father' s education and the length of sitting. Standardized regression coefficient ß comparison: Father' s education (-0.32) > family annual income (0.15) > mother' s education (0.09) > average daily sitting time (-0.02), with father' s education having the greatest impact, followed by family annual income. The length of sitting was positively related to the family' s annual income and the mother' s educational background, and negatively related to the total score of health literacy. Standardized regression coefficient ß comparison: Annual family income (0.14) > education background of mother (0.13)> total score of health literacy (-0.02), with the impact of annual family income the largest, followed by education background of mother. CONCLUSION: China' s first and second grade high school students generally spend a long time sitting every day, and the level of health literacy is generally low. The level of health literacy and sitting time are negatively correlated with each other, and are most influenced by the educational background of high school students' parents and their family economic levels.
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Letramento em Saúde , Humanos , Inquéritos e Questionários , Estudantes/psicologia , Renda , ChinaRESUMO
OBJECTIVE: To analyze the clinical effects of intraoperative transesophageal echocardiography (TEE) in different surgical methods for nephrectomy combined with Mayo â ¢-â £ inferior vena cave (IVC) tumor thrombectomy. METHODS: In the study, 28 patients who did surgery of nephrectomy and Mayo â ¢-â £ IVC thrombectomys in Peking University Third Hospital from 2022 January to 2024 February were included. Of the 28 patients, 16 patients did robotic surgery, 2 patients did laparoscopic surgery, and 10 patients did open surgery. All patients' clinical data were collected. RESULTS: Intra-operative TEE was used in 9 robotic surgeries, of which 7 cases showed image changes compared with preoperative image results. Intraoperative TEE indicated that tumor thrombus entered the right atrium in 2 cases, showed that tumor thrombus grade rose from Mayo â ¢ to Mayo â £ in 2 cases, and indicated that tumor thrombus adhered to IVC wall in 3 cases. All of these surgical plans were timely adjusted. Intra-operative TEE was used in 6 cases of open surgery, and 4 cases of them showed Mayo grade changes compared with preoperative image results. Intraoperative TEE indicated that tumor thrombus adhered to the IVC wall in 3 cases, and tumor thrombus adhered to the IVC wall with thrombus in one case. The surgical plans were adjusted, and the tumor thrombus was left or segmentally removed. Laparoscopic surgery did not use intraoperative TEE. The effects of intraoperative TEE included: the combination of exploration and TEE monitoring was used in open surgery, and tumor thrombus removal process was fully monitored by intraoperative TEE in the robotic surgery. Intraoperative TEE real-time monitored circulatory status and cardiac function changes. CONCLUSION: In different surgical methods for nephrectomy combined with Mayo â ¢-â £ tumor thrombectomy, intraoperative TEE can re-determine the tumor thrombus grade and degree of tumor thrombus adhered to IVC, track the tumor thrombus removal process in real-time, and monitor circulatory status and cardiac function changes. Intraoperative TEE plays an important role in different surgical methods, but its clinical application is still insufficient. Intraoperative TEE is recommended to such type of surgeries.