Search

Abstract Background This study aimed to explore the association between the stress hyperglycemia ratio (SHR) and short- and long-term outcomes in critically ill patients with sepsis. Methods This retrospective observational cohort study was conducted using the Medical Information Mart for Intensive Care-IV (MIMIC-IV v2.2) database. Patients were categorized into 4 SHR quartiles. The main focus was on in-hospital mortality and 1-year all-cause mortality as primary endpoints, while intensive care unit and hospital stays were considered as secondary outcomes. Regression and subgroup analyses were used to assess the correlation between SHR and the primary and secondary outcomes. Restricted cubic spline analysis was utilized to explore the nonlinear relationships between SHR and in-hospital and 1-year all-cause mortality. Results This study included two groups of patients, comprising 7456 and 6564 individuals. The in-hospital and 1-year mortality was 11.96% and 17.96% in Cohort 1 and 2, respectively. SHR was associated with an elevated risk of in-hospital mortality (OR: 2.08, 95%CI 1.66–2.61) and 1-year mortality (HR: 1.70, 95% CI 1.42–2.04). Patients in SHR quartile 4 had a higher risk of in-hospital (OR: 1.86, 95% CI 1.51–2.30) and 1-year (HR: 1.44, 95% CI 1.23–1.69) mortality than those in quartile 2. Restricted cubic spline analysis showed a “J-shaped” relationship between SHR and all-cause mortality in both cohorts. The relationship between high SHR and mortality remained consistent across almost all predefined subgroups. Conclusions Our study suggests that high SHR is associated with increased in-hospital and 1-year mortality in critically ill sepsis patients. Further investigations are needed to validate these results.

Abstract Numerous risk factors for oesophageal cancer are linked to lifestyle habits, but the role of early-life factors in its incidence and mortality is unclear. Using UK Biobank data, we explore the association among breastfeeding, maternal smoking, smoking in offspring, and oesophageal cancer risk in adult offspring via multivariable Cox regression. Here, we show that being breastfed, compared with not being breastfed, is associated with a lower risk of oesophageal cancer incidence (HR: 0.83, 95% CI: 0.70–0.98) and mortality (HR: 0.74, 95% CI: 0.61–0.89) in adult offspring. Additionally, it is associated with a reduced impact of smoking in offspring on oesophageal cancer incidence (HR: 0.79, 95% CI: 0.64-0.96) and mortality (HR: 0.73, 95% CI: 0.59-0.91). We subsequently construct a polygenic risk score for oesophageal cancer to explore the influence of genetic factors. Our findings emphasize the importance of breastfeeding, and smoking cessation to prevent oesophageal cancer.

Abstract In situ vaccination (ISV) triggers antitumor immune responses using the patient’s own cancer antigens, yet limited neoantigen release hampers its efficacy. Our novel combination therapy involves low-dose local cisplatin followed by ISV with a TLR7/8/9 agonist formulation (CR108), in which CR108 boosts and sustains the antitumor responses induced by the cisplatin-released neoantigens. In mouse models, the cisplatin+CR108 combination significantly outperformed cisplatin or CR108 alone in abrogating established 4T1 and B16 tumors. The synergistic antitumor effects of cisplatin and CR108 were accompanied by markedly increased tumor tertiary lymphatic structures (TLS) formation, higher levels of type I and III interferons and TNF-α in serum, augmented T and B lymphocyte infiltration, antigen-presenting cell activation, as well as reduced functionally of exhausted T cells. Single-cell sequencing analysis uncovered a potential pathway for TLS to serve as a reservoir for functional antitumor effector T cells. Furthermore, cisplatin+CR108 combo therapy, but neither cisplatin nor CR108 alone, effectively inhibited the growth of treated 4T-1 tumor in an effector T cell-dependent manner. Notably, the combo therapy also suppressed the growth of distant untreated 4T-1 tumors, demonstrating systemic antitumor effects. Moreover, combo-therapy led to full regression of 4T-1 tumors in a large percentage of mice, who became strongly resistant to secondary tumor challenge, a clear indication of antitumor immunological memory. The cisplatin+CR108 combo therapy holds promise in converting “cold” tumors into “hot” ones and eliciting robust antitumor immune responses in vivo.

Mitochondria and lysosomes are critical for neuronal homeostasis, as highlighted by their dysfunction in various neurological diseases. Recent studies have identified dynamic membrane contact sites between mitochondria and lysosomes, independent of mitophagy and the lysosomal degradation of mitochondrial-derived vesicles (MDVs), allowing bidirectional crosstalk between these cell compartments, the dynamic regulation of organelle networks, and substance exchanges. Emerging evidence suggests that abnormalities in mitochondria-lysosome contact sites (MLCSs) contribute to neurological diseases, including Parkinson’s disease, Charcot–Marie-Tooth (CMT) disease, lysosomal storage diseases, and epilepsy. This article reviews recent research advances regarding the tethering processes, regulation, and function of MLCSs and their role in neurological diseases.

Heavy metal pollution has become an increasingly serious environmental issue, making the detection of heavy metals essential for safeguarding public health and the environment. This review aims to highlight the commonly used methods for detecting heavy metals (such as atomic absorption spectroscopy (AAS), atomic emission spectroscopy (AES), inductively coupled plasma–mass spectrometry (ICP-MS), square-wave anodic stripping voltammetry (SWASV), etc.), with a particular focus on electrochemical detection and electrode modification materials. Metal nanomaterials (such as titanium dioxide (TiO2), copper oxide (CuO), ZIF-8, MXene, etc.) are emphasized as promising candidates for enhancing the performance of sensors due to their high surface area and excellent catalytic properties. However, challenges such as interference from non-target heavy metal ions and the formation of organometallic complexes with organic compounds can complicate the detection process. To address these issues, two potential solutions have been proposed: the development of advanced algorithms (such as machine learning (ML), back-propagation neural network (BPNN), support vector machines (SVM), random forests (RF), etc.) for signal processing and the use of pretreatment methods (such as Fenton oxidation (FO), ozone oxidation, and photochemical oxidation) to suppress such interferences. This paper aims to review commonly used methods for detecting heavy metals, with a particular emphasis on electrochemical techniques. It will also highlight the challenges faced in these methods, such as interference and sensitivity limitations, and propose innovative solutions, including the use of metal nanomaterials for improved sensor performance and the integration of advanced algorithms and pretreatment techniques to address interference and enhance detection accuracy.