Petroleum hydrocarbons and colored dissolved organic matter shape marine oil-degrading microbiota in different patterns.

Both petroleum hydrocarbons (PHCs) from oil pollution and colored dissolved organic matter (CDOM) have great influences on the marine microbial community as carbon source factors. However, their combined effects and the specific influence patterns have been kept unclear. This study selected the northeastern South China Sea (NSCS), a typical oil contaminated area, and investigated the characteristics of oil-degrading microbiota in the seawaters by high-throughput sequencing and the relationships with PHCs and CDOM as well as other environmental factors. The results showed the oil pollution had induced the enrichment of oil-degrading bacteria and oil-degrading functional genes, resulting in the core function of oil-degrading microbiota for shaping the microbial community. The Mantel test indicated carbon source factors played the dominant role in shaping the oil-degrading microbiota, compared with geographical distance and other non­carbon source factors. The influence patterns and strength of PHCs and CDOM on oil-degrading microbiota were further comprehensively analyzed. PHCs played a driving role in the differentiation of oil-degrading microbiota, while CDOM played a stabilizing role for the community similarity. The constructed structural equation model confirmed their distinct influence patterns and also explored the mediating effects of bulk organic carbon. This work not only revealed the important impact of oil pollution on marine microbial communities, but also made people realize the self-regulation ability of the marine environment through the endogenous organic matter.

Neoadjuvant envafolimab in a patient with MSI-H/dMMR colon cancer: a case report and literature review.

Clinical evidences of neoadjuvant immunotherapy in patients with mismatch repair deficient/microsatellite instability-high status (dMMR/MSI-H) colorectal cancer have not been well received. A 36-year-old man complained of recurrent right upper quadrant pain for more than 1 year, and the symptoms were not significantly relieved after 10 days of oral Changyanning tablet. The patient was finally diagnosed as dMMR/MSI-H colon cancer. Tumor regression was achieved after seven cycles of envafolimab treatment, and the patient obtained postoperative pathological complete response (pCR). Here, we report a case of MSI-H/dMMR transverse colon cancer, who obtained pCR after neoadjuvant envafolimab (a novel subcutaneous single-domain anti-PD-L1 antibody) with a favorable safety profile, aiming to enhance the experiences of comprehensive diagnosis and treatment of colon cancer.

Immune checkpoint inhibitors (ICIs) are a type of immunotherapy which can be used in the treatment of colorectal cancer. The authors here report the functions of envafolimab (a type of ICI) used before surgery to shrink tumor volume in colorectal cancer. A 36-year-old man suffered from repeated illness of right upper quadrant for over 1 year, and the illness were not recovered after 10 days of oral Changyanning tablet. The patient was finally diagnosed with colorectal cancer. After seven cycles of envafolimab treatment, tumor volume was significantly decreased, and the patient obtained favorable surgical outcomes with tolerable safety after surgery.

Supplemental L-arginine promotes hepatocyte proliferation and alters liver fatty acid metabolism in the late embryonic phase: an RNA-seq analysis.

The in ovo feeding (IOF) of L-arginine (L-Arg) to chick embryos is a viable method for improving early intestinal development, subsequently leading to an acceleration in growth rate during the posthatch stage. However, the liver, being the pivotal organ for energy metabolism in poultry, the precise effects and mechanisms of L-Arg on the liver development and metabolism remain unclear. To elucidate these, the present study injected 2 doses of L-Arg (10 mg/egg and 15 mg/egg) into the embryos of Hongyao chickens at 17.5 d of incubation, subsequently incubating them until d 19 for further analysis. IOF of 15 mg L-Arg/egg significantly increased the organ indices of liver and small intestine, as well as the duodenal villus height/crypt depth. RNA-Seq analysis of liver tissues showed that the metabolism of xenobiotics, amino acid metabolism, and the fatty acid metabolism were significantly enriched in L-Arg injection group. The core differentially expressed genes (DEGs) were primarily involved in cell proliferation and fatty acid metabolism. The CCK8 assays revealed that supplemental L-Arg significantly enhanced the proliferation of primary embryo hepatocytes and leghorn male hepatoma (LMH) cells. Upregulation of core DEGs, including HBEGF, HES4, NEK3, EGR1, and USP2, significantly promoted the proliferation of liver cells. Additionally, analysis of triglyceride and total cholesterol content, as well as oil red O staining, indicated that supplemental L-Arg effectively reduced lipid accumulation. Overall, L-Arg supplementation in late chick embryos may promote early liver and small intestine development by reducing liver lipid deposition and enhancing energy efficiency, necessitating further experimental validation. This study provides profound insights into the molecular regulatory network of L-Arg in promoting the development of chicken embryos. The identified DEGs that promote cell proliferation and lipid metabolism can serve as novel targets for further developing methods to enhance early development of chicken embryos.

Screening of reliable reference genes for the normalization of RT-qPCR in chicken liver tissues and LMH cells.

The liver plays a vital role in lipid synthesis and metabolism in poultry. To study the functional genes more effectively, it is essential to screen of reliable reference genes in the chicken liver, including females, males, embryos, as well as the Leghorn Male Hepatoma (LMH) cell line. Traditional reference gene screening involves selecting commonly used housekeeping genes (HKGs) for RT-qPCR experiments and using different algorithms to identify the most stable ones. However, this approach is limited in selecting the best reference gene from a small pool of HKGs. High-throughput sequencing technology may offer a solution to this limitation. This study aimed to identify the most consistently expressed genes by utilizing multiple published RNA-seq data of chicken liver and LMH cells. Subsequently, the stability of the newly identified reference genes was assessed in comparison to previously validated stable poultry liver expressed reference genes and the commonly employed HKGs using RT-qPCR. The findings indicated that there is a higher degree of similarity in stable expression genes between female and male liver (such as LSM14A and CDC40). In embryonic liver, the optimal new reference genes were SUDS3, TRIM33, and ERAL1. For LMH cells, the optimal new reference genes were ALDH9A1, UGGT1, and C21H1orf174. However, it is noteworthy that most HKGs did not exhibit stable expression across multiple samples, indicating potential instability under diverse conditions. Furthermore, RT-qPCR experiments proved that the stable expression genes identified from RNA-seq data outperformed commonly used HKGs and certain validated reference genes specific to poultry liver. Over all, this study successfully identified new stable reference genes in chicken liver and LMH cells using RNA-seq data, offering researchers a wider range of reference gene options for RT-qPCR in diverse situations.

Modified Sistrunk Procedure in 391 Pediatric Thyroglossal Duct Cyst Cases: Clinical Analysis of Efficacy and Recurrence Risk.

Objectives: The study aims to retrospectively summarize the clinical features of pediatric thyroglossal duct cyst (TGDC), investigate the efficacy of the modified Sistrunk (mSis) procedure, and analyze the recurrence risks. Methods: The clinical data of 391 children with TGDC admitted to Beijing Children's Hospital affiliated Capital Medical University and Baoding Children's Hospital from March 2012 to December 2021 were retrospectively analyzed. All patients underwent cervical ultrasound for preoperative evaluation. Twenty cases had magnetic resonance imaging and 8 cases had computed tomography for further evaluation. All patients underwent the standard mSis procedure, and clinical manifestations information, surgical information, complications, and prognosis were analyzed. Results: Among the 391 TGDC cases, 118 (30.2%) had a history of recurrent neck infection and 36 (9.2%) had undergone previous neck cyst and fistula resection surgeries, initially diagnosed as neck cyst (22 cases), TGDC (12 cases), or branchial fistula (2 cases), with only 6 cases having undergone partial hyoid bone resection in the previous operation. During the 15 to 156 months of follow-up, 10 children experienced local wound infection, but no other complications were reported. The recurrence rate was 2.30%, and the recurrence time ranged from 0.5 to 34 (average, 7.2) months post surgery. In the Poisson regression model examining factors related to recurrence, the P values of the 3 factors were <.05: clearness of the lesion boundary, surgical history, and maximum diameter and the relative risk (RR) values corresponding to the 3 risk factors, such as Exp (B), were 27.918, 10.054, and 6.606, respectively. Conclusions: The mSis procedure demonstrated safety and efficacy with fewer complications and a low recurrence rate of 2.30% in the study. Furthermore, the indistinct lesion boundary, surgical history, and large lesion diameter (>2 cm) were independent risk factors for recurrence in pediatric TGDC.Level of Evidence: IV.

Supercritical Fluid-extracted Citrus aurantium L. var. amara Engl. Essential Oil Nanoemulsion: Preparation, Characterization, and Its Sleep-promoting Effect.

To overcome the defects of Citrus aurantium L. var. amara Engl. essential oil (CAEO), such as high volatility and poor stability, supercritical fluid-extracted CAEO nanoemulsion (SFE-CAEO-NE) was prepared by the microemulsification method. Emulsifiers comprising Tween 80, polyoxyethylenated castor oil (EL-40), and 1,2-hexanediol, and an oil phase containing SFE-CAEO were used for microemulsification. We examined the physicochemical properties of SFE-CAEO-NE and steam distillation-extracted CAEO nanoemulsion (SDE-CAEO-NE), which were prepared using different concentrations of the emulsifiers. The mean particle size and zeta potential were 21.52 nm and -9.82 mV, respectively, for SFE-CAEO-NE, and 30.58 nm and -6.28 mV, respectively, for SDE-CAEO-NE, at an emulsifier concentration of 15% (w/w). SFE-CAEO-NE displayed better physicochemical properties compared with SDE-CAEO-NE. Moreover, its physicochemical properties were generally stable at different temperatures (-20-60℃), pH (3-8), and ionic strengths (0-400 mM). No obvious variations in particle size, zeta potential, and Ke were observed after storing this nanoemulsion for 30 days at 4℃, 25℃, and 40℃, suggesting that it had good stability. The sleep-promoting effect of SFE-CAEO-NE was evaluated using a mouse model of insomnia. The results of behavioral tests indicated that SFE-CAEO-NE ameliorated insomnia-like behavior. Moreover, SFE-CAEO- NE administration increased the serum concentrations of neurotransmitters such as 5-hydroxytryptamine and γ-aminobutyric acid, and decreased that of noradrenaline in mice. It also exerted a reparative effect on the function of damaged neurons. Overall, SFE-CAEO-NE displayed a good sleep-promoting effect.

NMR-based metabolomics approach to study the effect and related molecular mechanisms of Saffron essential oil against depression.

Depression currently ranks as the fourth leading cause of disability globally, affecting approximately 20% of the world's population. we established a chronic restraint stress (CRS) induced depression model in mice and employed fluoxetine as a reference drug. We assessed the therapeutic potential of saffron essential oil (SEO) and elucidated its underlying mechanisms through behavioral indices and NMR-based metabolomic analysis. The findings indicate that SEO ameliorates behavioral symptoms of depression, such as the number of entries into the central area, fecal count, latency to immobility, and duration of immobility in both the Tail Suspension Test (TST) and the Forced Swim Test (FST), along with correcting the dysregulation of 5-serotonin. Metabolomic investigations identified sixteen potential biomarkers across the liver, spleen, and kidneys. SEO notably modulated nine of these biomarkers: dimethylglycine, glycerol, adenosine, ß-glucose, α-glucose, uridine, mannose, sarcosine, and aspartate, with glycerol emerging as a common biomarker in both the liver and spleen. Pathway analysis suggests that these biomarkers participate in glycolysis, glycine serine threonine metabolism, and energy metabolism, potentially implicating a role in neural regulation. In summary, SEO effectively mitigates depressive-like behaviors in CRS mice, predominantly via modulation of glycolysis, amino acid metabolism, and energy metabolism, and potentially exerts antidepressant effects through neural regulation. Our study offers insights into small molecule metabolite alterations in CRS mice through a metabolomics lens, providing evidence for the antidepressant potential of plant essential oils and contributing to our understanding of the mechanisms of traditional Chinese medicine in treating depression.

Systematic review of the osteogenic effect of rare earth nanomaterials and the underlying mechanisms.

Rare earth nanomaterials (RE NMs), which are based on rare earth elements, have emerged as remarkable biomaterials for use in bone regeneration. The effects of RE NMs on osteogenesis, such as promoting the osteogenic differentiation of mesenchymal stem cells, have been investigated. However, the contributions of the properties of RE NMs to bone regeneration and their interactions with various cell types during osteogenesis have not been reviewed. Here, we review the crucial roles of the physicochemical and biological properties of RE NMs and focus on their osteogenic mechanisms. RE NMs directly promote the proliferation, adhesion, migration, and osteogenic differentiation of mesenchymal stem cells. They also increase collagen secretion and mineralization to accelerate osteogenesis. Furthermore, RE NMs inhibit osteoclast formation and regulate the immune environment by modulating macrophages and promote angiogenesis by inducing hypoxia in endothelial cells. These effects create a microenvironment that is conducive to bone formation. This review will help researchers overcome current limitations to take full advantage of the osteogenic benefits of RE NMs and will suggest a potential approach for further osteogenesis research.

Injectable Hydrogel Mucosal Vaccine Elicits Protective Immunity against Respiratory Viruses.

Intranasal vaccines, eliciting mucosal immune responses, can prevent early invasion, replication, and transmission of pathogens in the respiratory tract. However, the effective delivery of antigens through the nasal barrier and boosting of a robust systematic and mucosal immune remain challenges in intranasal vaccine development. Here, we describe an intranasally administered self-healing hydrogel vaccine with a reversible strain-dependent sol-gel transition by precisely modulating the self-assembly processes between the natural drug rhein and aluminum ions. The highly bioadhesive hydrogel vaccine enhances antigen stability and prolongs residence time in the nasal cavity and lungs by confining the antigen to the surface of the nasal mucosa, acting as a "mucosal mask". The hydrogel also stimulates superior immunoenhancing properties, including antigen internalization, cross-presentation, and dendritic cell maturation. Furthermore, the formulation recruits immunocytes to the nasal mucosa and nasal-associated lymphoid tissue (NALT) while enhancing antigen-specific humoral, cellular, and mucosal immune responses. Our findings present a promising strategy for preparing intranasal vaccines for infectious diseases or cancer.

Triiodothyronine induces a proinflammatory monocyte/macrophage profile and impedes cardiac regeneration.

Neonatal mouse hearts can regenerate post-injury, unlike adult hearts that form fibrotic scars. The mechanism of thyroid hormone signaling in cardiac regeneration warrants further study. We found that triiodothyronine impairs cardiomyocyte proliferation and heart regeneration in neonatal mice after apical resection. Single-cell RNA-Sequencing on cardiac CD45-positive leukocytes revealed a pro-inflammatory phenotype in monocytes/macrophages after triiodothyronine treatment. Furthermore, we observed that cardiomyocyte proliferation was inhibited by medium from triiodothyronine-treated macrophages, while triiodothyronine itself had no direct effect on the cardiomyocytes in vitro. Our study unveils a novel role of triiodothyronine in mediating the inflammatory response that hinders heart regeneration.

[Pathogenesis and Targeted Treatment Progress of Splenomegaly in Primary Myelofibrosis--Review].

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm with splenomegaly as the major clinical manifestation, which is commonly considered to be linked to splenic extramedullary hematopoiesis. Alteration of CXCL12/CXCR4 pathway can lead to the migration of hematopoietic stem cells and hematopoietic progenitor cells from bone marrow to spleen which results in splenic extramedullary hematopoiesis. In addition, low GATA1 expression and the abnormal secretion of cytokines were found to be significantly associated with splenomegaly. With the application of JAK1/2 inhibitors in clinical, the symptoms of splenomegaly have been significantly improved in PMF patients. This article will review the pathogenesis and targeted treatment progress of splenomegaly in PMF.

Multi-Omics Characteristics of Ferroptosis Associated with Colon Adenocarcinoma Typing and Survival.

BACKGROUND: Ferroptosis, an iron-dependent form of cell death, plays a crucial role in the progression of various cancers, including colon adenocarcinoma (COAD). However, the multi-omics signatures relevant to ferroptosis regulation in COAD diagnosis remain to be elucidated. METHODS: The transcriptomic, miRNAomic, and methylomic profiles of COAD patients were acquired from the Cancer Genome Atlas (TCGA). Ferroptosis activity in these patients was determined, represented by a ferroptosis score (FS), using single-sample gene set enrichment analysis (ssGSEA) based on the expression of ferroptosis-related genes. RESULTS: Results showed that the COAD patients with high-FS displayed favorable survival outcomes and heightened drug sensitivity. They also exhibited an up-regulation of genes involved in immune-related pathways (e.g., tumor necrosis factor signaling pathway), suggesting a correlation between immunity and ferroptosis in COAD progression. Furthermore, three survival prediction models were established based on 10 CpGs, 12 long non-coding RNAs (lncRNAs), and 14 microRNAs (miRNAs), respectively. These models demonstrated high accuracy in predicting COAD survival, achieving areas under the curve (AUC) >0.7. The variables used in the three models also showed strong correlations at different omics levels and were effective at discriminating between high-FS and low-FS COAD patients (AUC >0.7). CONCLUSIONS: This study identified different DNA methylation (DNAm), lncRNA, and miRNA characteristics between COAD patients with high and low ferroptosis activity. Furthermore, ferroptosis-related multi-omics signatures were established for COAD prognosis and classification. These insights present new opportunities for improving the efficacy of COAD therapy.

Safety and effectiveness of stent-assisted coiling with adjunctive techniques in ruptured acute aneurysms: a propensity score-matched cohort study.

OBJECTIVE: The use of stent-assisted coiling (SAC) in acute subarachnoid hemorrhage cases is associated with higher incidence rates of bleeding and ischemic complications. The aim of this study was to evaluate the safety and efficacy of the SAC technique in the treatment of ruptured intracranial aneurysms (RIAs). METHODS: A retrospective analysis was conducted on patients with RIAs treated with SAC or coiling alone (CA). Univariate analysis compared clinical information between the two groups. Propensity score matching was used to select patients for comparison and analyze surgical complications, prognosis, and imaging outcomes in both groups. RESULTS: A total of 394 aneurysms were included, and 272 aneurysms remained after application of propensity score matching, with an equal distribution of 136 cases in both the SAC and CA groups. There was no statistically significant difference in the immediate postoperative outcomes between the two groups (63.2% of SAC patients achieved class 1 on the Raymond-Roy occlusion classification scale vs 58.8% of CA patients, difference [95% CI] 4.4% [-0.076 to 0.163]; 33.1% achieved class 2 vs 38.2%, 5.1% [-0.065 to 0.170]; 3.7% achieved class 3 vs 2.9%, 0.8% [-0.047 to 0.062], p = 0.506). At the 1-year follow-up, the SAC group exhibited higher rates of complete occlusion (59.5% vs 42.4%, 17.1% [0.040-0.294]) and stability (24.0% vs 19.2%, 4.8% [-0.061 to 0.156]), while experiencing lower rates of improvement (12.4% vs 22.4%, 10.0% [0.001-0.201]) and recanalization (4.1% vs 16.0%, 11.9% [0.036-0.120]), with statistically significant differences in these outcomes (p < 0.001). No significant disparities were observed in clinical outcomes in terms of modified Rankin Scale (mRS) scores at discharge (76.5% vs 77.2% had mRS score 0-2, 0.7% [-0.098 to 0.113]; 23.5% vs 22.8% had mRS score 3-6, 0.7% [-0.098 to 0.113], p = 0.886) and 1-year follow-up (90.8% vs 92.2% had mRS score 0-2, 1.4% [-0.063 to 0.091]; 9.2% vs 7.8% had mRS score 3-6, 1.4% [-0.063 to 0.091], p = 0.683). Intraoperative rupture occurred more frequently in the SAC group compared with the CA group, although the difference was not statistically significant (5.1% vs 2.9%, 2.2% [-0.035 to 0.081], p = 0.356). The SAC group demonstrated a higher incidence of intraoperative thrombosis, but the difference was not statistically significant (8.1% vs 2.9%, 5.2% [-0.010 to 0.117], p = 0.063). Postoperative thrombosis in the SAC group was 3 times higher, but this difference was not statistically significant (6.6% vs 2.2%, 4.4% [-0.013, 0.106], p = 0.076). The surgery-related mortality rates did not differ significantly between the two groups (4.4% vs 5.9%, 1.5% [-0.048 to 0.077], p = 0.583). CONCLUSIONS: Although stent treatment for RIA results in some incidents of complications, it is safe and effective. Besides, the SAC group showed better vascular imaging results compared with the CA group.

Involvement of PI3K/AKT Pathway in the Rapid Antidepressant Effects of Crocetin in Mice with Depression-Like Phenotypes.

The current first-line antidepressants have the drawback of slow onset, which greatly affects the treatment of depression. Crocetin, one of the main active ingredients in saffron (Crocus sativus L.), has been demonstrated to have antidepressant activities, but whether it has a rapid antidepressant effect remains unclear. This study aimed to investigate the onset, duration, and mechanisms of the rapid antidepressant activity of crocetin (20, 40 and 80 mg/kg, intraperitoneal injection) in male mice subjected to chronic restraint stress (CRS). The results of behavioral tests showed that crocetin exerted rapid antidepressant-like effect in mice with depression-like phenotypes, including rapid normalization of depressive-like behaviors within 3 h, and the effects could be maintained for 2 days. Hematoxylin-eosin (HE) and Nissl staining showed that crocetin ameliorated hippocampal neuroinflammation and nerve injuries in mice with depression-like phenotypes. The levels of inflammatory factors, corticosterone and pro brain-derived neurotrophic factor in crocetin-administrated mice serum were significantly reduced compared with those in the CRS group, as well as the levels of inflammatory factors in hippocampus. What's more, Western blot analyses showed that, compared to CRS-induced mice, the relative levels of mitogen-activated kinase phosphatase 1 and toll-like receptor 4 were significantly reduced after the administration of crocetin, and the relative expressions of extracellular signal-regulated kinase 1/2 (ERK1/2), cAMP-response element binding protein, phosphorylated phosphoinositide 3 kinase (p-PI3K)/PI3K, phosphorylated protein kinase B (p-AKT)/AKT, phosphorylated glycogen synthase kinase 3ß (p-GSK3ß)/GSK3ß, phosphorylated mammalian target of rapamycin (p-mTOR)/mTOR were markedly upregulated. In conclusion, crocetin exerted rapid antidepressant effects via suppressing the expression of inflammatory cytokines and the apoptosis of neuronal cells through PI3K/AKT signaling pathways. The rapid antidepressant effect of crocetin (40 mg/kg) could be maintained for at least 2 days after single treatment.

The functional study of a novel MKRN3 missense mutation associated with familial central precocious puberty.

Central precocious puberty (CPP) refers to a syndrome of early puberty initiation with a characteristic increase in the release of gonadotropin-releasing hormone (GnRH); therefore, it is also called GnRH-related precocious puberty. About a quarter of idiopathic central precocious puberty (ICPP) may be familial. Studies suggest that mutations of makorin ring finger protein 3 (MKRN3) can cause familial central precocious puberty (FCPP). In this report, we describe a Chinese female patient carrying a novel MKRN3 variant (c.980G>A/p.Arg327His) and presenting the CPP phenotype. This novel variant attenuated its own ubiquitination, degradation, and inhibition on the transcriptional and translational activity of GNRH1, which was verified through functional tests. We can consider this variant as a loss-of-function mutation, which subsides the inhibition of GnRH1-related signaling and gives rise to GnRH-related precocious puberty.

A dual-responsive ratiometric indicator designed for in vivo monitoring of oxidative stress and antioxidant capacity.

The imbalance between oxidative stress and antioxidant capacity is strongly associated with the development of numerous degenerative diseases, including cardiovascular diseases, diabetes, neurodegenerative diseases, and cancer. Therefore, monitoring oxidative stress and antioxidant capacity in vivo is crucial for maintaining cellular homeostasis and the stability of the organism's internal environment. Here, we present the findings of our study on DQ1, a dual-responsive indicator designed specifically for imaging H2O2 and NAD(P)H, which are critical indicators of oxidative stress and antioxidant capacity. DQ1 facilitated the colorimetric and fluorescence detection of H2O2 and NAD(P)H in two well-separated channels, exhibiting a detection limit of 1.0 µM for H2O2 and 0.21 nM for NAD(P)H, respectively. Experiments conducted on living cells and zebrafish demonstrated that DQ1 could effectively detect changes in H2O2 and NAD(P)H levels when exposed to exogenous hypoxic conditions and chemical stimuli. Furthermore, the effectiveness of the as-fabricated indicator was investigated in two distinct mouse models: evaluating H2O2 and NAD(P)H levels in myocardial cell dysfunction during acute myocardial infarction and liver tissue damage under trichloroethylene stress conditions. In vivo experiments demonstrated that the levels of the two cardiac biomarkers increase progressively with the development of myocardial infarction, eventually reaching a steady state after 7 days when the damaged cells in the infarcted region become depleted. Moreover, during 14 continuous days of exposure to trichloroethylene, the two biomarkers in liver tissue exhibited a sustained increase, indicating a significant enhancement in intracellular oxidative stress and antioxidant capacity attributed to the mouse liver's robust metabolic capacity. The aforementioned studies underscore the efficacy of DQ1 as a valuable tool for scrutinizing redox states at both the single-cell and biological tissue levels. It presents significant potential for investigating the dynamic alternations in oxidative stress and antioxidant capacity within disease models as the disease progresses, thereby facilitating a more profound comprehension of these processes across various disease models.

Bioparameter-directed nanoformulations as MRI CAs enable the specific visualization of hypoxic tumour.

A malignant tumour has hypoxic cells of varying degrees. The more severe the hypoxic degree, the more difficult the prognosis of the tumour and the higher the recurrence rate. Therefore, tumour hypoxia imaging is crucial. Magnetic resonance imaging (MRI) shows its strength in high resolution, depth of penetration and noninvasiveness. However, it needs more excellent contrast agents (CAs) to combat the complex tumour microenvironment (TME) and increased targeting of tumours to enhance clinical safety. Many research studies have focused on developing hypoxia-responsive MRI CAs that take advantage of the unique characteristics of hypoxic tumours. The low oxygen pressure, acidic TME, and up-regulated redox molecule levels found in hypoxic tumours serve as biological stimuli for nanoformulations that can accurately image the hypoxic region. This review highlights the importance of developing bioparameter-directed nanoformulations as MRI CAs for accurate tumour diagnosis. The design strategies and mechanisms of tumour-hypoxia imaging with nanoformulations are exemplified, with a focus on pH-responsiveness, redox-responsiveness, and p(O2)-responsiveness. The promising future of bioparameter-responsive nanoformulations for accurate tumour diagnosis and personalised cancer treatment is discussed.

The value of total tumor diameter in unilateral multifocal papillary thyroid carcinoma: a propensity score matching analysis.

Background: Tumor multifocality is frequently observed in papillary thyroid carcinoma (PTC). However, the maximum tumor diameter (MTD), currently utilized in various staging schemes, might not accurately indicate the level of aggressiveness exhibited by multifocal tumors. We aimed to investigate the relationship between total tumor diameter (TTD) and clinicopathological features of papillary thyroid carcinoma. Methods: Retrospective data analysis was done on 1936 individuals who underwent complete thyroidectomy for PTC. Patients were classified into subgroups according to unilateral multifocality, central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM). The relationships of clinicopathological features among these groups were analyzed. Results: Unilateral multifocality was observed in 117 patients. The clinicopathological features of the unilateral multifocal PTC were similar to the unifocal PTC with approximate TTD. The unilateral multifocality played no independent role in CLNM and LLNM. Moreover, the efficiency of TTD in predicting CLNM and LLNM was significantly higher than that of MTD. Conclusion: In the case of unilateral multifocal PTC, TTD is a more accurate indicator of the biological characteristics of the tumor than MTD.

Communications between macrophages and cardiomyocytes.

The heart is a muscular organ that pumps blood throughout the body and is one of the most vital organs in human body. While cardiomyocytes are essential for maintaining the normal function of the heart, a variety of cardiovascular diseases such as coronary artery occlusion, arrhythmia, and myocarditis can lead to cardiomyocyte death, resulting in deterioration of heart function. The adult mammalian heart is incapable of regenerating sufficient cardiomyocytes following cardiac injuries, eventually leading to heart failure and death. Cardiac macrophages are ubiquitously distributed in the healthy heart and accumulated at the site of injury. Macrophages play essential roles in regulating homeostasis and proliferation of cardiomyocyte, promoting electrical conduction, and removing dead cardiomyocytes and debris through direct and indirect cell-cell crosstalk. In this review, we summarize the latest insights into the role of macrophages in maintaining cardiac homeostasis and the macrophage-cardiomyocyte crosstalk in both healthy and injured scenarios. Video Abstract.

Interaction between high interleukin-2 and high cortisol levels is associated with psychopathology in patients with chronic schizophrenia.

BACKGROUND: Both cortisol and interleukins appear at abnormal levels in schizophrenia. Our previous study has shown that cortisol and interleukins are associated with psychopathology and response to antipsychotic medications in a relatively small sample size of patients with schizophrenia. The current study was designed to investigate how cortisol, interleukins (ILs) and their interactions would correlate with clinical presentation in a relatively large sample size of patients with schizophrenia. METHODS: We compared serum cortisol, IL-2, IL-6, and IL-8 levels in 162 medicated schizophrenia patients (including 27 patients in remission) and 62 healthy controls. Serum levels of cortisol and interleukins were measured by radioimmunoassay and quantitative ELISA, respectively. Clinical symptoms were assessed according to the Positive and Negative Syndrome Scale (PANSS). RESULTS: Patients with schizophrenia had significantly higher levels of cortisol and IL-2 compared to controls. Patients in remission had higher levels of IL-6 than non-remitting patients. PANSS positive symptoms, general psychopathology, cortisol and IL-2 were the most central nodes in the cortisol-IL-symptom network. The interaction between cortisol and IL-2 was associated with PANSS positive symptoms, general psychopathology and depressive factor. For patients with cortisol level above the median, IL-2 was negatively associated with PANSS positive symptoms and general psychopathology. CONCLUSIONS: Our results indicated that the interaction between cytokines and cortisol may be associated with the pathophysiology of some symptoms in chronic schizophrenia. In particular, the interaction between cortisol and IL-2 is associated with the clinical phenotypes of schizophrenia.