RESUMO

Glycolytic metabolic reprogramming in cancer is regulated by both cancer intrinsic variations like isocitrate dehydrogenase 1 (IDH1) status and non-cancerous microenvironment components like tumor associated macrophages (TAMs). However, the detailed mechanism remains elusive. Here, we identify hexosaminidase B (HEXB) as a key regulator for glycolysis in glioblastoma (GBM). HEXB intercellularly manipulates TAMs to promote glycolysis in GBM cells, while intrinsically enhancing cancer cell glycolysis. Mechanistically, HEXB elevation augments tumor HIF1α protein stability through activating ITGB1/ILK/YAP1; Subsequently, HIF1α promotes HEXB and multiple glycolytic gene transcription in GBM cells. Genetic ablation and pharmacological inhibition of HEXB elicits substantial therapeutic effects in preclinical GBM models, while targeting HEXB doesn't induce significant reduction in IDH1 mutant glioma and inhibiting IDH1 mutation-derived 2-hydroxyglutaric acid (2-HG) significantly restores HEXB expression in glioma cells. Our work highlights a HEXB driven TAMs-associated glycolysis-promoting network in GBM and provides clues for developing more effective therapies against it.

Assuntos

Neoplasias Encefálicas , Carcinogênese , Glioblastoma , Glicólise , Subunidade alfa do Fator 1 Induzível por Hipóxia , Isocitrato Desidrogenase , beta-N-Acetil-Hexosaminidases , Humanos , Glioblastoma/genética , Glioblastoma/patologia , Glioblastoma/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Linhagem Celular Tumoral , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Carcinogênese/genética , Camundongos , beta-N-Acetil-Hexosaminidases/metabolismo , beta-N-Acetil-Hexosaminidases/genética , Microambiente Tumoral/imunologia , Regulação Neoplásica da Expressão Gênica , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/imunologia , Integrina beta1/metabolismo , Integrina beta1/genética , Glutaratos/metabolismo , Mutação , Proteínas de Sinalização YAP/metabolismo

RESUMO

Introduction: Microorganisms exhibit intricate interconnections with tea plants; however, despite the well-established role of microorganisms in crop growth and development, research on microbes within the tea plant remains insufficient, particularly regarding endophytic microorganisms. Methods: In this study, we collected samples of leaves and rhizosphere soils from 'Zhuyeqi', 'Baojing Huangjincha#1', 'Baiye#1', and 'Jinxuan' varieties planted. Results: Our analyses revealed significant variations in tea polyphenol contents among tea varieties, particularly with the 'Zhuyeqi' variety exhibiting higher levels of tea polyphenols (>20% contents). Microbiome studies have revealed that endophytic microbial community in tea plants exhibited higher host specificity compared to rhizospheric microbial community. Analyses of across-ecological niches of the microbial community associated with tea plants revealed that soil bacteria serve as a significant reservoir for endophytic bacteria in tea plants, Bacillus may play a crucial role in shaping the bacterial community across-ecological niche within the tea plants with higher tea polyphenol levels. In the aforementioned analyses, the microbial community of 'Zhuyeqi' exhibited a higher degree of host specificity for leaf endophytic microorganisms, the topological structure of the co-occurrence network is also more intricate, harboring a greater number of potential core microorganisms within its nodes. A closer examination was conducted on the microbial community of 'Zhuyeqi', further analyses of its endophytic bacteria indicated that its endophytic microbial community harbored a greater abundance of biomarkers, particularly among bacteria, and the enriched Methylobacterium and Sphingomonas in 'Zhuyeqi' may play distinct roles in disease resistance and drought resilience in tea plants. Conclusion: In summary, this study has shed light on the intricate relationships of tea plant varieties with their associated microbial communities, unveiling the importance of microorganisms and tea varieties with higher tea polyphenols, and offering valuable insights to the study of microorganisms and tea plants.

RESUMO

BACKGROUND: Research on the role of transcatheter heart valve (THV) deformation and calcium distribution in patients with bicuspid aortic valves (BAVs) undergoing transcatheter aortic valve replacement (TAVR) remains limited. OBJECTIVES: The aim of this study was to evaluate the impact of THV deformation on clinical outcomes in individuals with BAVs undergoing TAVR and the influence of calcium on these outcomes. METHODS: In total, 229 consecutive patients with BAVs who underwent TAVR with balloon-expandable valves and had computed tomography (CT) performed 30 days post-TAVR were analyzed. Patients were stratified into 3 groups: group 1 (n = 125), with no THV underexpansion or eccentricity; group 2 (n = 69), with underexpansion or eccentricity; and group 3 (n = 35), with both. Calcium distribution was assessed using CT, and its associations with clinical outcomes, including all-cause mortality at 3 years and leaflet thrombosis at 30 days, were determined. A subgroup analysis of patients with type 1 BAVs was conducted. RESULTS: Group 3 exhibited higher rates of all-cause mortality than the other groups, along with the highest risk for hypoattenuated leaflet thickening at 30 days. Multivariate analysis identified annular and left ventricular outflow tract calcification as independent predictors of all-cause mortality and hypoattenuated leaflet thickening. In patients with type 1 BAVs, excessive calcification at the raphe and opposite leaflet were associated with all-cause mortality at 3 years. CONCLUSIONS: THV deformation post-TAVR was significantly linked to all-cause mortality in patients with BAVs. Annular and left ventricular outflow tract calcification correlated with increased risks for all-cause mortality and leaflet thrombosis. (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Thrombosis and Its Treatment With Anticoagulation [RESOLVE]; NCT02318342).

Assuntos

Estenose da Valva Aórtica , Valva Aórtica , Valvuloplastia com Balão , Doença da Válvula Aórtica Bicúspide , Calcinose , Doenças das Valvas Cardíacas , Próteses Valvulares Cardíacas , Desenho de Prótese , Substituição da Valva Aórtica Transcateter , Humanos , Masculino , Feminino , Doença da Válvula Aórtica Bicúspide/diagnóstico por imagem , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/mortalidade , Substituição da Valva Aórtica Transcateter/instrumentação , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Valva Aórtica/fisiopatologia , Valva Aórtica/anormalidades , Resultado do Tratamento , Fatores de Risco , Fatores de Tempo , Calcinose/diagnóstico por imagem , Calcinose/fisiopatologia , Calcinose/mortalidade , Valvuloplastia com Balão/efeitos adversos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/mortalidade , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/fisiopatologia , Doenças das Valvas Cardíacas/cirurgia , Doenças das Valvas Cardíacas/mortalidade , Estudos Retrospectivos , Medição de Risco , Trombose/diagnóstico por imagem , Trombose/etiologia , Tomografia Computadorizada Multidetectores , Valor Preditivo dos Testes

RESUMO

The primary pathological change in Parkinson's disease (PD) is the progressive degeneration of dopaminergic neurons in the substantia nigra. Additionally, excessive microglial activation and synaptic loss are also typical features observed in PD samples. Exercise trainings have been proven to improve PD symptoms, delay the disease progression as well as affect excessive microglial synaptic phagocytosis. In this study, we established a mouse model of PD by injecting mouse-derived α-synuclein preformed fibrils (M-α-syn PFFs) into the substantia nigra, and demonstrated that treadmill exercise inhibits microglial activation and synaptic phagocytosis in striatum. Using RNA-Seq and proteomics, we also found that PD involves excessive activation of the complement pathway which is closely related to over-activation of microglia and abnormal synaptic function. More importantly, exercise training can inhibit complement levels and complement-mediated microglial phagocytosis of synapses. It is probably triggered by CD55, as we observed that CD55 in the striatum significantly increased after exercise training and up-regulation of that molecule rescued motor deficits of PD mice, accompanied with reduced microglial synaptic phagocytosis in the striatum. This research elucidated the interplay among microglia, complement, and synapses, and analyzed the effects of exercise training on these factors. Our work also suggested CD55 as a complement-relevant candidate molecule for developing therapeutic strategies of PD.

Assuntos

Antígenos CD55 , Proteínas do Sistema Complemento , Camundongos Endogâmicos C57BL , Doença de Parkinson , Fagocitose , Condicionamento Físico Animal , Sinapses , Regulação para Cima , Animais , Fagocitose/fisiologia , Camundongos , Condicionamento Físico Animal/fisiologia , Condicionamento Físico Animal/métodos , Regulação para Cima/fisiologia , Sinapses/metabolismo , Sinapses/patologia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Doença de Parkinson/terapia , Proteínas do Sistema Complemento/metabolismo , Antígenos CD55/metabolismo , Microglia/metabolismo , Masculino , alfa-Sinucleína/metabolismo , Modelos Animais de Doenças

RESUMO

Leading by the antiviral activities against HSV-2 virus, bioactivity-guided the fraction of crude alkaloids from seeds of Peganum harmala led to the isolation of nine structurally novel indole alkaloids, pegaharolines A - I (1-9), and 11 known ones (10-20). Compound 3 was an unusual 6/5/5/5 spirotetracyclic indole-derived alkaloids featuring a classic bicyclic indole unit fused with an additional pyrrolizine ring via a spiral atom (C-3). Compound 4 was determined as a novel indole alkaloid, characterized with a rare hexacyclic 6/5/6/5-6/6 ring system, by a single-crystal X-ray diffraction. Compounds 5 and 6 were peculiar indole dimers featuring with the rare carbon skeleton of an octacyclic scaffold. Compounds 1-6 were six racemates. Most compounds exhibited different levels of antiviral activities against HSV-2. Especially, the anti-HSV-2 activity of compound 1 (IC50 = 0.90 ±â€¯0.10 µM) was much better than that of the positive control (acyclovir, IC50 = 1.12 ±â€¯0.15 µM). In this study, the discovery of anti-HSV-2 components from the seeds of P. harmala, could benefit development and utilization of this plant in antiviral medicinal products.

RESUMO

BACKGROUND: α-Hemolysin, encoded by hla, is a major virulence factor of Staphylococcus aureus. Sequence type (ST) 45 is a globally spread clone with increasing clinical prevalence in Taiwan. Our previous study showed that among the CC45 isolates, the spa type t1081 isolates presented greater hemolytic activity. MATERIALS AND METHODS: The hemolytic activity of 67 CC45 isolates (44 t1081 and 23 non-t1081) from clinical blood cultures was assessed using rabbit red blood cells. The sequences of hla and its upstream regulatory regions and RNAIII were compared between the two groups. The expression of hla and its regulators RNAIII, mgrA, and saeR was analyzed via qRT‒PCR, while Hla protein levels were measured via Western blotting. RESULTS: Compared with non-t1081 isolates, t1081 isolates presented increased hemolytic activity. No significant differences in hla sequences, upstream regulatory regions, or gene expression levels were detected between the two groups. The expression of the transcriptional regulators mgrA and saeR was also similar between the two groups. Western blotting revealed increased Hla protein in the t1081 isolates. However, neither the sequence or expression of RNAIII, a regulator of hla at both the transcriptional and posttranscriptional levels, differed between the groups. CONCLUSION: Our study revealed that, compared with other CC45 isolates, the t1081/ST45 isolates presented greater hemolytic activity. This heightened activity was due mainly to increased Hla protein levels. Moreover, the higher translation levels may be independent of the known regulator RNAIII, indicating a potential RNAIII-independent mechanism for Hla regulation.

RESUMO

Chloro-haloacetonitrile (Cl-HAN), belongs to a group of nitrogenous disinfection by-products (N-DBPs) found in surface water, and are known to pose a major risk to the safety of human drinking water. However, the exact biological toxicity mechanism and the extent of the stress response caused by Cl-HAN remain unclear, resulting in a lack of effective measures to control its presence. Thus, the quantitative toxicological genomics and bioinformatics methods were applied to explore the effects of three chloro-haloacetonitriles (Cl-HANs) on the transcription of fusion genes under varying concentrations of stress in E. coli over 2-hour period. The initial stress response and their toxic mechanism were analyzed. The study also identified the molecular toxicity endpoint, and the core genes that are responsible for the specific toxicity of different Cl-HANs. Cl-HANs exhibited concentration-dependent characteristics of toxic effects, and caused changes in gene expression related oxidative and membrane stress. The stress response results showed that dichloroacetonitrile (dCAN) still caused significant DNA damage under the lowest concentration stress. Chloroacetonitrile (CAN) and trichloroacetonitrile (tCAN) exhibited lower genetic toxicity levels at 513 µg/L and 10.7 µg/L, respectively. The toxic effects of tCAN were widespread. And there was a good correlation between the molecular endpoint (EC-TELI1.5) and the phenotypic endpoint (LD50) with rp=-0.8634 (P=0.0593). In all concentrations of stress in CAN, dCAN, and tCAN, the number of overexpressed genes shared was 15, 2, and 14, respectively. Furthermore, bioinformatics analysis demonstrated that Cl-HANs affected genes associated with general stress pathways, such as cell biochemistry and physical homeostasis, resulting in changes in biological processes. And for CAN-induced DNA damage, polA played a dominant role, while katG, oxyR, and ahpC were the core genes involved in oxidative stress induced by dCAN and tCAN, respectively. These findings provide valuable data for the toxic effect of Cl-HANs.

Assuntos

Acetonitrilas , Dano ao DNA , Escherichia coli , Poluentes Químicos da Água , Acetonitrilas/toxicidade , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Poluentes Químicos da Água/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Desinfetantes/toxicidade

RESUMO

As the global energy structure evolves and clean energy technologies advance, electrocatalysis has become a focal point as a critical conversion pathway in the new energy sector. Transitional metal electrocatalysts (TMEs) with their distinctive electronic structures and redox properties show great potential in electrocatalytic reactions. However, complex reaction mechanisms and kinetic limitations hinder the improvement of energy conversion efficiency, highlighting the necessity for comprehensive studies on structure and performance of electrocatalysts. X-ray Absorption Fine Structure (XAFS) spectra stand out as a robust tool for examining the electrocatalyst's structures and performance due to its atomic selectivity and sensitivity to local environments. This review delves into the application of XAFS technology in characterizing TMEs, providing in-depth analyses of X-ray Absorption Near-Edge Structure (XANES) spectra, and Extended XAFS (EXAFS) spectra in both R-space and k-space. These analyses reveal intrinsic structural information, electronic interactions, catalyst stability, and aggregation morphology. Furthermore, the paper examines advancements in in-situ XAFS techniques for real-time monitoring of active site changes, capturing critical intermediate and transitional states, and elucidating the evolution of active species during electrocatalytic reactions. These insights deepen our understanding on structure-activity relationship of electrocatalysts and offer valuable guidance for designing and developing highly active and stable electrocatalysts.

RESUMO

Background: Emergency medicine (EM) is a growing specialty both clinically and academically. Academic EM development can be measured by number of scientific publications. This study aimed to evaluate the academic international cooperation trend of Taiwan emergency departments (EDs) in the past two decades using social network analysis (SNA). Methods: The study population were publications with first author affiliated with Taiwan EDs and the study duration was publication year before 2021. The enrolled publications were categorized into two groups: Group one, all authors were affiliated with Taiwan (domestic publications) and Group two, authors were affiliated with Taiwan and other countries (international publications). The primary outcome measurement was the degree centrality of Taiwan before 2021. The secondary outcome measurements included the trend in annual publication number of Group one and Group two, the trend in country number of each year in Group two, the top five countries that collaborate with Taiwan, the difference between the median of citation numbers in Group one and Group two, and the difference between the median of author numbers in Group one and Group two. Results: A total 4,363 publications were enrolled, of which 4,046 publications were classified in Group one and 317 publications were in Group two. The annual publication number of both groups increased significantly. The annual country number of collaboration with Taiwan ED publications had also significantly increased. The median of citation number and author number in Group two were both significantly higher than Group one. The top five countries collaborating with Taiwan were the United States, China, Malaysia, Japan, and Australia. Conclusions: Taiwan EDs' growing international collaboration in the past two decades indicated a capacity to conduct multi-country research. International collaboration publications obtained higher citations compared to domestic publications. Researchers should enhance international collaborations for academic advancement.

RESUMO

SARS-CoV-2 causes COVID-19, with symptoms ranging from mild to severe, including pneumonia and death. This beta coronavirus has a 30-kilobase RNA genome and shares about 80 % of its nucleotide sequence with SARS-CoV-1. The replication/transcription complex, essential for viral RNA synthesis, includes RNA-dependent RNA polymerase (RdRp, nsp12) enhanced by nsp7 and nsp8. Antivirals like molnupiravir and remdesivir, which are RdRp inhibitors, treat severe COVID-19 but have limitations, highlighting the need for new therapies. This study assessed (-)-cytisine, methylcytisine, and thermopsine derivatives against SARS-CoV-1 and SARS-CoV-2 in vitro, focusing on their RdRp inhibition. Selected compounds from a previous study were evaluated using a SARS-CoV-2 RNA polymerase assay kit to investigate their structure-activity relationships. Compound 17 (1,3-dimethyluracil conjugate with (-)-cytisine and thermopsine) emerged as a potent inhibitor of SARS-CoV-1 and SARS-CoV-2 RdRp, with an IC50 value of 7.8 µM against SARS-CoV-2 RdRp. It showed a dose-dependent reduction in cytopathic effects in cells infected with SARS-CoV-1 and SARS-CoV-2 replicon-based single-round infectious particles (SRIPs) and significantly inhibited SARS-CoV N protein expression, with EC50 values of 0.12 µM for SARS-CoV-1 and 1.47 µM for SARS-CoV-2 SRIPs. Additionally, compound 17 reduced viral subgenomic RNA levels in a concentration-dependent manner in SRIP-infected cells. The structure-activity relationships of compound 17 with SARS-CoV-1 and SARS-CoV-2 RdRp were also investigated, highlighting it as a promising lead for developing antiviral agents against SARS and COVID-19.

RESUMO

The bioaccumulation of heavy metals due to metallurgical and smelting activities threatens human health. Although microbial-induced carbonate/phosphate precipitation (MICP/MIPP) technology has been applied to heavy metal remediation, the relative merits of MICP and MIPP, especially under extreme pH environments, have not yet been documented. In this study, Sporosarcina pasteurii (SP)-based MICP and Bacillus megaterium (BM)-based MIPP were applied to immobilize lead (Pb) in aqueous solution and loess soil. The results showed that the BM retained a strong phosphorolysis ability when under strongly acidic conditions, while the ureolysis ability of SP approached zero. Furthermore, the bioprecipitates obtained under BM-based MIPP had a denser appearance, presumably due to the enrichment of calcite and apatite crystals. The results also showed that Pb immobilization was achieved through bacterial adsorption, the chelate function of sodium glycerophosphate (SGP), large organic matter complexation, and biomineralization through the MICP/MIPP mechanism. Under SP-based MICP, SP and large organic matter immobilized Pb2+ at rates of 17.6 % and 31.7 %, respectively, while under BM-based MIPP, BM, organic matter, and SGP immobilized Pb2+ at rates of 21.5 %, 23.4 %, and 48.5 % respectively. The MICP and MIPP mechanisms dominated Pb immobilization at rates of 78.6 % and 99.6 %, respectively.

RESUMO

The understanding of cellular energy metabolism activation by engineered scaffolds remains limited, posing challenges for therapeutic applications in tissue regeneration. This study presents biosynthesized poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] and its major degradation product, 3-hydroxybutyrate (3HB), as endogenous bioenergetic fuels that augment cellular anabolism, thereby facilitating the progression of human bone marrow-derived mesenchymal stem cells (hBMSCs) towards osteoblastogenesis. Our research demonstrated that 3HB markedly boosts in vitro ATP production, elevating mitochondrial membrane potential and capillary-like tube formation. Additionally, it raises citrate levels in the tricarboxylic acid (TCA) cycle, facilitating the synthesis of citrate-containing apatite during hBMSCs osteogenesis. Furthermore, 3HB administration significantly increased bone mass in rats with osteoporosis induced by ovariectomy. The findings also showed that P(3HB-co-4HB) scaffold substantially enhances long-term vascularized bone regeneration in rat cranial defect models. These findings reveal a previously unknown role of 3HB in promoting osteogenesis of hBMSCs and highlight the metabolic activation of P(3HB-co-4HB) scaffold for bone regeneration.

RESUMO

BACKGROUND: Infertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin level on female reproduction remain unclear. METHODS: Transgenic pigs overexpressing leptin (♀) were produced by backcrossing and screened for leptin overexpression. The growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single-nucleus RNA sequencing (snRNA-seq) of the leptin-overexpressing pigs and wild-type group were evaluated. RESULTS: Transgenic pigs overexpressing leptin (♀) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested a late onset of puberty (330 ± 54.3 vs. 155 ± 14.7 days), irregular estrous behavior characterized by increased inter-estrous interval (29.2 ± 0 vs. 21.3 ± 0.7 days), and more number of matings until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum cholesterol esters along with steroidogenic markers (StAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells in the ovaries. Moreover, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Furthermore, snRNA-seq reflected that leptin overexpression triggered immune response, suppressed follicle development and luteinization, resulting in metabolic dysfunction and hormone imbalance in the ovary. CONCLUSIONS: Low body weight in leptin overexpressing pigs adversely affects the reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, an increased immune response, and altered ovarian functions. This study provides a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressing female pigs.

Assuntos

Animais Geneticamente Modificados , Leptina , Reprodução , Animais , Feminino , Leptina/sangue , Suínos , Reprodução/fisiologia , Modelos Animais de Doenças

RESUMO

Phosphorus concentration on the surface of seawater varies greatly with different environments, especially in coastal. The molecular mechanism by which cyanobacteria adapt to fluctuating phosphorus bioavailability is still unclear. In this study, transcriptomes and gene knockouts were used to investigate the adaptive molecular mechanism of a model coastal cyanobacterium Synechococcus sp. PCC 7002 during periods of phosphorus starvation and phosphorus recovery (adding sufficient phosphorus after phosphorus starvation). The findings indicated that phosphorus deficiency affected the photosynthesis, ribosome synthesis, and bacterial motility pathways, which recommenced after phosphorus was resupplied. Even more, most of the metabolic pathways of cyanobacteria were enhanced after phosphorus recovery compared to the control which was kept in continuous phosphorus replete conditions. Based on transcriptome, 54 genes potentially related to phosphorus-deficiency adaptation were selected and knocked out individually or in combination. It was found that five mutants showed weak growth phenotype under phosphorus deficiency, indicating the importance of the genes (A0076, A0549-50, A1094, A1320, A1895) in the adaptation of phosphorus deficiency. Three mutants were found to grow better than the wild type under phosphorus deficiency, suggesting that the products of these genes (A0079, A0340, A2284-86) might influence the adaptation to phosphorus deficiency. Bioinformatics analysis revealed that cyanobacteria exposed to highly fluctuating phosphorus concentrations have more sophisticated phosphorus acquisition strategies. These results elucidated that Synechococcus sp. PCC 7002 have variable phosphorus response mechanisms to adapt to fluctuating phosphorus concentration, providing a novel perspective of how cyanobacteria may respond to the complex and dynamic environments. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00244-y.

RESUMO

The formation of black odour water is primarily attributed to the elevated concentration of organic pollutants, along with an excessive amount of nitrogen and phosphorus, ultimately leading to an anoxic aquatic environment. The water temperature influence mechanism on black-odorous water restoration by microporous aeration is still lacking depth study. This paper selected (15-18) ℃ (spring and autumn), (22-25) ℃ (summer), (8-11) ℃ (winter) as temperature conditions, and investigated temperature influence on nitrogen reduction. Researches showed that: (1) The removal rates of COD, NH4+-N and TN were significantly positively correlated with temperature (r = 0.99, 0.96, 0.97), the lowest removal rates were 83.16%, 95.68%, 58.7% ((8-11) ℃), the highest values were 92.67%, 98.27%, 70.96% ((22-25) ℃), respectively. (2) At a temperature range of 22-25°C, the microbial community exhibited the highest levels of abundance, diversity, and uniformity. Notably, Proteobacteria dominated this temperature range with a relative abundance of 79.72%. Furthermore, temperature positively correlated with the majority of dominant bacterial species, suggesting that conditions at 22-25°C are highly conducive to the growth of most bacterial communities. Among these, Limnohabitans, Alsobacter, and Candidatus_Aquirestis, which possess key functions in denitrification and nitrogen removal, displayed significantly higher abundances. It explains the positive correlation between temperature and removal rates of COD, TN and NH4+-N from microbial population's perspective. Thus, the best temperature for repairing black-smelly water is (22-25) ℃. This study provides technical reference for mechanism research and practical application of microporous aeration.

RESUMO

Background: In bronchiectasis, nontuberculous mycobacteria (NTM) lung disease (NTM-LD) is a well-known coexisting infection. However, microorganism coisolates and clinical NTM-LD predictors are poorly studied. Methods: Patients with bronchiectasis diagnosed by means of computed tomography between January 2017 and June 2020 were screened, using the date of computed tomography as the index date. Those with a major bronchiectasis diagnosis in ≥2 follow-up visits after the index date were enrolled in the study, and NTM-LD occurrence and its association with pneumonia and hospitalization within 1 year were analyzed. Results: Of the 2717 participants, 79 (2.9%) had NTM-LD diagnosed. The factors associated with NTM-LD included hemoptysis, postinfectious bronchiectasis, a tree-in-bud score ≥2, a modified Reiff score ≥4, and chronic obstructive pulmonary disease (adjusted odds ratios, 1.80, 2.36, 1.78, 2.95, and 0.51, respectively). Compared with patients in the non-NTM group, those with NTM-LD had higher rates of hospitalization (15.9% vs 32.9%; P < .001) and pneumonia (9.8% vs 20.3%; P = .003). Pseudomonas aeruginosa was the most common microorganism in those with NTM-LD and those in the non-NTM group (10.1% vs 7.8%; P = .40). However, compared with those in the non-NTM group, Acinetobacter baumannii and Escherichia coli were more prevalent in patients with NTM-LD (0.7% vs 3.8% [P = .03%] and 1.0% vs 3.8% [P = .05], respectively). Conclusions: Postinfectious bronchiectasis with hemoptysis, higher radiological involvement, and a tree-in-bud pattern were associated with NTM-LD risk. The rate of A baumannii and E coli coisolation was higher in bronchiectasis populations with NTM-LD.

RESUMO

The immunosuppressive tumor microenvironment (TME) has become a major challenge in cancer immunotherapy, with abundant tumor-associated macrophages (TAMs) playing a key role in promoting tumor immune escape by displaying an immunosuppressive (M2) phenotype. Recently, it was reported that M1 macrophage-derived nanovesicles (M1NVs) can reprogram TAMs to an anti-tumor M1 phenotype, thereby significantly alleviating the immunosuppressive TME and enhancing the anti-tumor efficacy of immunotherapy. Herein, we developed M1NVs loaded with mesoporous dopamine (MPDA) and indocyanine green (ICG), which facilitated the recruitment of M2 TAMs through synergistic photothermal and photodynamic therapy. Thereafter, M1NVs can induce M1 repolarization of TAMs, resulting in increased infiltration of cytotoxic T lymphocytes within the tumor to promote tumor regression. This study investigated the effect of phototherapy on the immune environment of liver cancer using single-cell RNA sequencing (scRNA-seq) by comparing HCC tissues before and after MPDA/ICG@M1NVs + NIR treatment. The results showed significant shifts in cell composition and gene expression, with decreases in epithelial cells, B cells, and macrophages and increases in neutrophils and myeloid cells. Additionally, gene analysis indicated a reduction in pro-inflammatory signals and immunosuppressive functions, along with enhanced B-cell function and anti-tumor immunity, downregulation of the Gtsf1 gene in the epithelial cells of the MPDA/ICG @M1NVs + NIR group, and decreased expression of the lars2 gene in immune subpopulations. Eno3 expression is reduced in M1 macrophages, whereas Clec4a3 expression is downregulated in M2 macrophages. Notably, the B cell population decreased, whereas Pou2f2 expression increased. These genes regulate cell growth, death, metabolism, and tumor environment, indicating their key role in HCC progression. This study highlights the potential for understanding cellular and molecular dynamics to improve immunotherapy.

RESUMO

BACKGROUND/AIM: Definitive radiotherapy is the main treatment modality for patients with locally advanced stage lung cancer and a good performance status who are ineligible for surgery. Respiration-controlled radiotherapy (RCRT) has been recommended, but its effectiveness has been debated in the literature. Therefore, we aimed to study the efficacy of RCRT in definitive radiotherapy for locally advanced-stage lung cancer. PATIENTS AND METHODS: We identified lung cancer patients diagnosed between 2011 and 2021 using data from the Taiwan Cancer Registry and related databases. In our primary analysis, we applied propensity score weighting (PSW) to balance observable potential confounders. We then compared the hazard ratio (HR) of death between the RCRT group and the non-RCRT group. Additionally, we conducted a comprehensive assessment of other outcomes and performed various supplementary analyses. RESULTS: The primary analysis included 3,020 patients. Overall survival did not significantly differ between the RCRT group and the non-RCRT group, with a PSW-adjusted HR of 0.79 (95% confidence interval=0.49-1.28, p=0.342). These findings were consistent with other outcomes and supplementary analyses. CONCLUSION: In locally advanced-stage lung cancer patients who received definitive radiotherapy, survival did not significantly differ between those treated with RCRT and those treated without RCRT. To our knowledge, this is the first population-based study on this topic.

Assuntos

Neoplasias Pulmonares , Estadiamento de Neoplasias , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Taiwan/epidemiologia , Resultado do Tratamento , Idoso de 80 Anos ou mais , Respiração , Sistema de Registros , Pontuação de Propensão

RESUMO

[This corrects the article DOI: 10.1016/j.heliyon.2024.e32290.].