Search Results (58,063)

The deterioration of the global climate and accelerated urbanization have led to intense pressure on surface space resources. As a strategic development field, deep underground space has become a crucial direction for alleviating human habitation pressure. However, current research on deep underground space mostly focuses on fields such as geology and medicine, while the design of habitable environments lacks interdisciplinary integration and systematic approaches. Taking deep underground space as the research object, this study first clarifies the interdisciplinary research context through bibliometric analysis. Then, combined with geological data (ground temperature, groundwater, and ground stress, etc.) from major cities in China, it defines the characteristics of the in situ environment and the characteristics of the development and utilization of deep underground space. By comparing the habitable design experiences of extreme environments, such as space stations, Moon habitats, and desert survival modules, the study extracts five categories of design elements: natural conditions, construction status, social economy, users, and existing resources. Ultimately, it establishes a demand-oriented, five-dimensional habitable design methodology covering in situ environment adaptation, living support, medical and health services, resilience and flexibility, and existing space renovation. This research clarifies the differentiated design strategies for hundred-meter-level and kilometer-level deep underground spaces, providing theoretical support for the scientific development of deep underground space and serving as a reference for habitable design in other extreme environments. Full article

Salmonella is a major zoonotic pathogen and phage cocktails offer a novel strategy against its infections. This study aimed to characterize Salmonella phages and assess the efficacy of various phage combinations, both in vitro and in vivo. Three phages (PJN012, PJN042, PJN065) were isolated, showing stability across a broad range of temperatures and pH values, and lacking genes associated with lysogenicity, virulence, and antibiotic resistance. Combined with two known phages (PJN025, vB_SalS_JNS02), they formed cocktails tested for lytic activity against S. Enteritidis and S. Typhimurium. Phage cocktails (comprising 2–5 phages) that demonstrated efficacy in vitro were validated using Galleria mellonella models. For S. Enteritidis strain 015, prophylactic cocktail C18 increased larval survival to 90% at 48 h (vs. 3% control). For S. Typhimurium strain 024, phage cocktail 26 showed the best therapeutic effect when co-injected with the bacterium, with a survival rate of up to 85% at 96 h, compared to 30% in the positive control group. Biofilm assays showed cocktails inhibited formation more effectively (e.g., at 24 h, C14 and C17 reduced biofilm formation by 93.74% and 94.21%, respectively) than removed established ones. The cocktails depended on bacterial type, phage genera, combinations, and incubation time. Robust in vitro screening remains crucial for optimizing phage formulations despite potential in vivo discrepancies. Full article

Background: p73, a member of the p53 family of transcription factors, plays important roles in DNA repair, cell proliferation, angiogenesis, invasion, metastasis, immune evasion, and cytotoxic therapy response. The clinicopathological significance of p73 in breast cancer, particularly in the context of TP53 mutation, remains largely unknown. Methods: Clinicopathological significance of p73 and p53 protein expression was evaluated in 1369 invasive BC and 317 ductal carcinomas in situ (DCIS), including in p53 wild-type or p53 mutant tumours. p73 transcripts and splice variants were investigated in breast cancer genomes (TCGA). Results: High cytoplasmic p73 was significantly associated with high tumour grades, high pleomorphism scores, high mitotic scores, high risk Nottingham prognostic index, negative expression of oestrogen receptors (ERs), triple negative phenotypes (all p values ≤ 0.01), and poor breast cancer specific survival (BCSS) (p = 0.013). In TP53 mutant breast cancers, high p73 was significantly associated with aggressive histopathological features (all p ≤ 0.001) and poor BCSS (p = 0.001) but not in p53 wild-type tumours. Conclusions: Cytoplasmic p73 may be a marker of aggressive phenotype and worse prognosis, particularly in p53 mutant breast cancer. p73, in conjunction with altered p53 expression, may be involved in breast cancer pathogenesis. Full article

Cold stress poses a critical threat to fish survival by triggering metabolic dysfunction, oxidative damage, immune suppression, and apoptosis. However, hybrid polyploid fish triploid crucian carp (3nRCR, 3n = 150) demonstrate superior stress tolerance. In this study, we investigated the cold adaptation mechanisms in different ploidy cyprinid fishes: triploid crucian carp compared to its diploid improved red crucian carp (Carassius auratus red var., RCC, 2n = 100, ♀) and improved allotetraploid (4nAT, 4n = 200, ♂) progenitors. Under controlled cooling, 3nRCR lost equilibrium at a significantly lower temperature (3.2 °C) than RCC (4.0 °C) and 4nAT (4.5 °C), confirming its superior enhanced cold resistance. Histological examination revealed minimal tissue damage in 3nRCR, characterized by reduced gill inflammation and cellular apoptosis. Transcriptomics revealed triploid-specific molecular strategies: 3nRCR uniquely activated retinol metabolism and metabolic rewiring (arginine/proline metabolism, oxidative phosphorylation). Notably, in the immune-related NLR signaling pathway, both nlrp1 and nlrp3 (key inflammasome components) were significantly downregulated in 3nRCR (p < 0.01). In contrast, genes involved in endoplasmic reticulum (ER) stress response, including chop and nrf2, were markedly upregulated, indicating a reinforced cellular stress resolution mechanism absent in both RCC and 4nAT. Our results demonstrate that triploid cold adaptation is orchestrated through a balanced interaction among mitochondrial apoptosis, ER stress, and inflammasome pathways. These findings provide novel insights into hybrid polyploid adaptation mechanisms and targets for cold-resilient aquaculture breeding. Full article

Background and Clinical Significance: In gastric cancer, splenic metastases are found in less than 7% of cases and are usually associated with other systemic secondary determinations; much more rarely, they represent the sole secondary determination of the malignant disease. Case presentation: In this paper, we present the case of a 64-year-old patient who underwent curative surgery for gastric adenocarcinoma 10 months ago and, during oncological monitoring, was diagnosed with a splenic tumor formation with intense metabolic activity on PET-CT examination, raising suspicion of splenic metastases. The medical team observed an increase in carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and Cluster of Differentiation (CD) 276 values, along with a slight decrease in Dickkopf Related Protein 3 (DKK 3). Considering that the spleen was the only site of secondary localization of the malignant disease, the patient underwent laparoscopic splenectomy with histopathological confirmation of the presence of gastric adenocarcinoma. There are no signs of loco-regional or distant recurrence 15 months postoperatively. In patients with radical excision of gastric cancer who present only with splenic metastases, splenectomy is indicated and is associated with good disease-free survival. If other secondary manifestations of malignant gastric disease are identified or suspected, chemotherapy treatment and the wait-and-see approach are recommended, as the patient does not have a real benefit from splenectomy. Until now, there is no standard protocol for the diagnostic and therapeutic management of patients with gastric cancer and metachronous splenic metastases; thus, the development of a decision-making scheme for these situations is necessary. Conclusions: The multidisciplinary approach, including the tumor board and an infectious disease specialist, are important steps in the effective management of these cases. The role of new biological markers such as CD 276 and DKK 3 for assessing the progression of malignant disease could constitute a new direction for research. Full article

Cushing’s syndrome is one of the most common endocrine disorders in dogs and is typically managed with long-term medical treatment. Several pharmacological agents are available: trilostane, mitotane, ketoconazole, cabergoline, selegiline, and aminoglutethimide, but their comparative effects on survival remain unclear. This systematic review and meta-analysis compared the impact of these agents on survival outcomes in dogs with naturally occurring diseases. A comprehensive search of MEDLINE, Embase, Web of Science, Academic Search Complete, and the Cochrane Library was conducted between 1 September 2024 to 3 January 2025. Eligible studies included dogs diagnosed with Cushing’s syndrome that reported survival outcomes for at least one of the specified treatments. Five studies (n = 295 dogs) met the inclusion criteria, with trilostane and mitotane providing sufficient data for meta-analysis. Pooled mean difference in survival time across four studies was 85.1 days (95% CI: −255.9 to 85.7, p = 0.21) with substantial heterogeneity (I² = 89%), indicating no statistically significant difference between the drugs. In contrast, pooled survival rates at fixed intervals favored trilostane, with an 11% higher survival at 36 months (p = 0.005) and no heterogeneity observed (I² = 0%). These findings suggest trilostane may offer long-term survival benefits over mitotane. Full article

Background and Objectives: Ixekizumab is a human monoclonal antibody targeting interleukin-17A, approved for the treatment of moderate-to-severe plaque psoriasis. Given its demonstrated efficacy and safety in clinical trials, this study aimed to evaluate the real-world drug survival of Ixekizumab and identify clinical predictors of treatment discontinuation. Materials and Methods: A retrospective, observational, hospital-based study was conducted in the Department of Dermatology at the Central University Hospital of Asturias (HUCA). Patients with moderate-to-severe plaque psoriasis who initiated treatment with Ixekizumab (Taltz^®) between 8 June 2017 and 10 October 2024, were included. Demographic data, comorbidities, age at disease onset, family history, PASI score, and previous treatments were recorded. Drug survival was assessed using Kaplan–Meier survival curves and the log-rank test. Predictors of discontinuation were analyzed using univariate and multivariate Cox proportional hazards models. Results: A total of 103 patients (55.3% women) were included. Drug survival rates were 85% at one year, 73% at two years, and 61% at four years, with a mean treatment duration of 52.5 months (95% CI: 46.01–58.99). Multivariate analysis showed that patients under the age of 65 had a significantly higher risk of treatment discontinuation (hazard ratio: 1.813; p < 0.05). The most common reason for discontinuation was secondary treatment failure (45.16%). Ixekizumab demonstrated sustained drug survival in a real-world setting, with rates falling within the mid-to-upper range reported in the literature. Older age (>65 years) was associated with greater treatment persistence, highlighting a potential influence of age on long-term therapeutic adherence. Full article

Background/Objectives: Colorectal neuroendocrine carcinomas (NECs) are rare, aggressive tumors with poorly defined clinicopathologic and molecular features. Their biological behavior and optimal treatment strategies remain unclear. Additionally, a subset of anorectal NECs may be associated with high-risk human papillomavirus (HPV) infection, suggesting potential heterogeneity in pathogenesis. Methods: We retrospectively reviewed 12 cases of colorectal NECs. Clinical outcomes, histologic morphology, immunohistochemistry, molecular profiling, including common oncogenic mutations, and HPV status were analyzed. Results: Seven cases demonstrated small cell NECs, and five showed large cell NECs. The majority of NECs (n = 9) arose in the rectum. TP53 mutations were the most common (75%), followed by KRAS, RB1, FBXW7, and BRAF mutations. One case demonstrated mismatch repair (MMR) deficiency. High-risk HPV was detected in one rectal NEC, which lacked common oncogenic mutations and was the only long-term survivor (54 months). p16 expression did not correlate consistently with HPV in situ hybridization (ISH) status. Among small cell NECs with follow-up, platinum-based chemotherapy resulted in significantly longer survival than FOLFOX (13.5 vs. 4 months, p = 0.0209). Conclusions: Colorectal NECs display histologic and molecular heterogeneity. The tumors of small cell NECs potentially benefit more from platinum-based chemotherapy. HPV-associated NECs may represent a distinct subset with better prognosis, but p16 is not a reliable surrogate marker. Routine subclassification into small vs. large cell types and comprehensive molecular profiling, including HPV testing, may aid clinical decision-making and prognostication. Full article

Introduction: Renal cell carcinoma (RCC) develops metastatic disease in 30–50% of patients during their disease course, with approximately one quarter presenting with metastases at diagnosis. While the lungs, liver, bones, brain, and adrenal glands are the most frequent metastatic sites, duodenal involvement is exceptionally rare. This uncommon presentation poses diagnostic and therapeutic challenges, particularly regarding the role of surgical resection in the metastatic setting. Objective: We aim to evaluate the clinical presentation, management strategies, and outcomes of patients with duodenal metastasis from RCC, with particular emphasis on the potential role of surgery, through a systematic review of the literature. Methods: A comprehensive electronic search of Medline, Embase, and Scopus was conducted according to PRISMA guidelines. The following MeSH terms were applied: Kidney Neoplasms [MeSH] AND Duodenal Neoplasms/metastasis [MeSH]. Eligible studies included original reports or case series describing RCC with duodenal metastasis. Demographic, clinical, surgical, and survival data were extracted and synthesized. Results: Of 89 records identified, 83 underwent full-text review and 51 met inclusion criteria, representing 55 patients. The median age at diagnosis was 64 years, and 80% of primary tumors arose from the right kidney. Nearly all patients (98%) were symptomatic, most commonly with upper gastrointestinal bleeding, anemia, or obstructive features. Pancreaticoduodenectomy was the predominant surgical approach, performed with curative intent in selected cases. Patients undergoing surgery achieved a 5-year overall survival of 70%, compared with 0% among non-operated patients. Conclusions: Duodenal metastasis from RCC remains an uncommon entity, limiting the strength of available evidence. Nevertheless, our findings suggest that surgical management—when feasible and decided within a multidisciplinary framework—can provide meaningful survival benefit and should be considered as a complement to contemporary systemic therapies for metastatic RCC Full article

Oxidative stress (OxS) is a central factor in neurodegenerative diseases (NDs), including Parkinson’s disease (PD). Phenolic compounds, including flavonoids and coumarins, counteract reactive species and modulate key intracellular survival pathways, highlighting their therapeutic potential. Parastrephia quadrangularis (Pq), a plant from the Atacama Desert traditionally used by Andean communities, contains phenolic compounds with antioxidant, antifungal, and anti-inflammatory activities. However, its neuroprotective potential remains unexplored. Here, a hydroalcoholic extract (HAE) of Pq and four subfractions (MeOH, EtOAc, DCM, and n-hex) were obtained and assessed for in vitro antioxidant activity, with HAE selected for its consistent activity. In SH-SY5Y cells, HAE-Pq lowered basal reactive oxygen species and attenuated hydrogen peroxide-induced OxS. The UHPLC-MS analysis of HAE-Pq unveiled a high abundance of flavonoids, followed by coumarins and phenolic acids, and identified 16 additional metabolites, including jaceidin as the most abundant. In vivo assays using a Drosophila genetic PD model induced by overexpression of human α-synuclein, showed that HAE-Pq was non-toxic and non-aversive and that it delayed the onset of motor defects by one week in female flies. This study provides the first evidence of the neuroprotective potential of Pq, supporting its value as a source of bioactive metabolites relevant to NDs and reinforcing its ethnopharmacological validation. Full article

Background/Objectives: Cancer survivors can develop heart conditions such as aortic valve disease because of age and other shared risk factors. If this valve condition becomes symptomatic, the prognosis is poor if the valve is not replaced. Surgical aortic valve replacement (SAVR) is one mode of treatment. Methods: Of 2500 consecutive patients who underwent SAVR with a biological valve, 388 patients were cancer survivors. They were compared for preoperative characteristics, operative parameters, postoperative adverse events, need for resources, and long-term survival. For the latter, the six most common tumors (prostate, breast, colorectal, bladder, pulmonary, and hematologic) and the effect of the interval between cancer treatment and cardiac surgery were scrutinized. Results: Cancer increased significantly over time. Pulmonary and kidney disease differed between the groups, but cardiac comorbid conditions did not. Operative parameters, early adverse events, and need for resources did not differ. Median survival time was significantly reduced in cancer survivors: 104 (97–112) versus 119 (116–122) months, and this was driven by an interval of less than 5 years and prior lung cancer. Prior cancer was the least important of ten predictors for long-term mortality. Conclusions: The outcome of cancer survivors after SAVR is acceptable. For patients with pulmonary cancer, the outcome is poor. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by its aggressive clinical behavior and intricate microenvironment regulation, leading to dismal prognosis. Elucidating the molecular mechanisms underlying PDAC pathogenesis is crucial for developing improved therapeutic approaches. The functional significance and molecular basis of transcobalamin 1 (TCN1) in PDAC remain largely unexplored. Methods and Results: Through integrated analysis of TCGA and GTEx datasets combined with 80 clinical specimens, we identified significant TCN1 overexpression in PDAC, showing a positive association with tumor stage and negative associations with histological differentiation and overall survival. Functional investigations showed that TCN1 enhanced pancreatic cancer cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) in both in vitro and in vivo models. Mechanistically, TCN1 physically interacts with signal transducer and activator of transcription 4 (STAT4) to enhance its transcriptional activity. Chromatin immunoprecipitation (ChIP) assays showed that STAT4-mediated transcriptional activation of dual oxidase 2 (DUOX2) occurs through direct promoter binding. As a pivotal reactive oxygen species (ROS)-generating enzyme, DUOX2 overexpression elevates intracellular ROS levels, thereby promoting EMT progression and activating proliferation-related signaling cascades. Antioxidant treatment effectively abrogated TCN1-driven oncogenic phenotypes, establishing ROS as the critical downstream mediator. Conclusions: Collectively, our findings reveal a novel TCN1/STAT4/DUOX2 regulatory axis that exacerbates PDAC progression by remodeling redox homeostasis. This signaling cascade may serve as a prognostic biomarker and a potential therapeutic target for ROS-directed precision therapy in PDAC. Full article

Nocardiosis is an infection caused by Gram-positive, saprophytic bacteria most often affecting immunocompromised hosts. The lungs, central nervous system, and skin are the sites most typically involved, although any organ may be affected. Skeletal involvement, particularly osteomyelitis, remains uncommon. This study is a review of all published cases of Nocardia osteomyelitis in humans, emphasizing epidemiology, microbiology, clinical features, management, and patient outcomes. A narrative review was performed using data from the PubMed/MedLine and Scopus databases. Fifty studies describing 55 patients were included. The median age was 54 years, and 65.5% were male. The main risk factors were immunosuppression (21.8%) and trauma (18.2%). The vertebrae constituted the most commonly affected site (25.5%), followed by the lower limb bones (20%); 23.6% had multifocal disease. Nocardia asteroides accounted for the majority of cases (34.8%). Trimethoprim-sulfamethoxazole was the most frequently administered agent (81.5%), followed by cephalosporins (29.6%) and carbapenems (27.8%). Overall mortality was 9.3%, with 5.6% of reported deaths directly attributed to the infection. Although uncommon, osteomyelitis due to Nocardia spp. should be considered when Gram-positive, filamentous microorganisms are detected in bone specimens, particularly in immunocompromised or post-trauma patients, as early suspicion and targeted therapy may improve survival. Full article

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and remains a major cause of mortality in intensive care units. Methods: We analyzed plasma levels of sTREM-1, CRP, PCT, sCD14-ST, HMGB1, IL-6, IL-10, vitamin D (VD), and sHLA-G in patients with SIRS/sepsis, and assessed their relationships with APACHE II, SOFA scores, and survival. Results: Septic patients showed significantly elevated sTREM-1, CRP, PCT, sCD14-ST, and higher neutrophil-to-lymphocyte ratio, while VD levels were markedly reduced. Logistic regression identified CRP and PCT as the strongest univariate predictors of sepsis, but after adjustment for age, sex, BMI, and comorbidities, CRP lost significance, whereas VD and sCD14-ST remained independent predictors. Prognostically, higher IL-10 levels significantly correlated with 7- and 28-day mortality and with SOFA scores, while higher VD concentrations predicted better survival. Conclusion: CRP, PCT, and sCD14-ST are reliable diagnostic biomarkers of sepsis, with sTREM-1 providing additional value for disease monitoring. After adjustment for clinical covariates, VD emerged as an independent protective factor, whereas elevated IL-10 significantly predicted 7- and 28-day mortality. These findings underscore the utility of combining inflammatory and immunoregulatory biomarkers to improve sepsis diagnostics and prognostication, warranting validation in larger multicenter cohorts. Full article

Background/Objectives: Selenoproteins play indispensable roles in embryonic development, with their dysregulation linked to various metabolic and neurological disorders. This study aims to systematically quantify the mRNA expression levels of all 24 selenoprotein genes in murine heart, brain, liver, and kidney tissues across embryonic (E8.5, E12.5, E18.5) and postnatal (P7, P30, P90) developmental stages, in order to elucidate the regulatory landscape of selenium metabolism during development. Methods: We collected tissues from mice at six developmental stages and performed RNA extraction followed by quantitative real-time PCR (qPCR) to measure the expression of all 24 selenoprotein genes. Data were normalized using the geometric mean of ActB and Gapdh, and statistical analyses were conducted using one-way ANOVA with Duncan’s post hoc test. Results: Our analysis reveals three principal findings: (1) Distinct expression patterns emerge among selenoprotein families—deiodinases (Dio1-3) and thioredoxin reductases (Txnrd1-3) exhibit limited embryonic expression (<20-fold changes), while glutathione peroxidases (Gpx1, Gpx3, Gpx4) and biosynthesis-related genes (Selenop, Msrb1) show substantial postnatal upregulation (up to 600-fold increases); (2) Selenoproteins essential for embryonic survival (Gpx4, Txnrd1, Txnrd2, Selenoi, Selenot) display expression profiles concordant with their essential developmental functions; (3) Selenop and Msrb1, involved in selenium transport and redox regulation, demonstrate early embryonic upregulation with further increases during postnatal development. Conclusions: These spatiotemporal expression patterns elucidate the regulatory landscape of selenium metabolism during development and provide mechanistic insights into the phenotypes associated with selenium deficiency. The findings offer valuable implications for human nutritional interventions and developmental health. Full article