Multiomics analysis reveal the impact of 17α-Ethinylestradiol on mortality in juvenile zebrafish.

17α-Ethinylestradiol (EE2) is known for its endocrine-disrupting effects on embryonic and adult fish. However, its impact on juvenile zebrafish has not been well established. In this study, juvenile zebrafish were exposed to EE2 at concentrations of 5 ng/L (low dose, L), 10 ng/L (medium dose, M), and 50 ng/L (high dose, H) from 21 days post-fertilization (dpf) to 49 dpf. We assessed their growth, development, behavior, transcriptome, and metabolome. The findings showed that the survival rate in the EE2-H group was 66.8 %, with all surviving fish displaying stunted growth and swollen, transparent abdomens by 49 dpf. Moreover, severe organ deformities were observed in the gills, kidneys, intestines, and heart of fish in both the EE2-H and EE2-M groups. Co-expression analysis of mRNA and lncRNA revealed that EE2 downregulated the transcription of key genes involved in the cell cycle, DNA replication, and Fanconi anemia signaling pathways. Additionally, metabolomic analysis indicated that EE2 influenced metabolism and development-related signaling pathways. These pathways were also significantly identified based on the genes regulated by lncRNA. Consequently, EE2 induced organ deformities and mortality in juvenile zebrafish by disrupting signaling pathways associated with development and metabolism. The results of this study offer new mechanistic insights into the adverse effects of EE2 on juvenile zebrafish based on multiomics analysis. The juvenile zebrafish are highly sensitive to EE2 exposure, which is not limited to adult and embryonic stages. It is a potential model for studying developmental toxicity.

Pericyte phenotype switching alleviates immunosuppression and sensitizes vascularized tumors to immunotherapy in preclinical models.

T cell-based immunotherapies are a promising therapeutic approach for multiple malignancies, but their efficacy is limited by tumor hypoxia arising from dysfunctional blood vessels. Here, we report that cell-intrinsic properties of a single vascular component, namely the pericyte, contribute to the control of tumor oxygenation, macrophage polarization, vessel inflammation, and T cell infiltration. Switching pericyte phenotype from a synthetic to a differentiated state reverses immune suppression and sensitizes tumors to adoptive T cell therapy, leading to regression of melanoma in mice. In melanoma patients, improved survival is correlated with enhanced pericyte maturity. Importantly, pericyte plasticity is regulated by signaling pathways converging on Rho kinase activity, with pericyte maturity being inducible by selective low-dose therapeutics that suppress pericyte MEK, AKT, or notch signaling. We also show that low-dose targeted anticancer therapy can durably change the tumor microenvironment without inducing adaptive resistance, creating a highly translatable pathway for redosing anticancer targeted therapies in combination with immunotherapy to improve outcome.

Unmet Medication Needs and the Association with Mortality in Older Adults: Equality-Oriented Monitoring toward Universal Health Coverage.

With population aging becoming a global trend, the unmet medication needs of older individuals are steadily increasing, potentially leading to a decline in quality of life and increased mortality. To identify unmet medication needs and inequality, and the association with health outcomes. A total of 69,443 participants in 31 countries from five international cohorts of aging were included. We measured the unmet medication needs level across sociodemographic strata. We developed an equality-oriented health care service coverage index (ESCI) and explored its relation to all-cause mortality in older adults over 55 years of age. Unmet medication needs in older adults with chronic conditions reached 41.84%. The highest unmet needs were observed in older age groups and participants with multimorbidity. The ESCI was further constructed by covering both the unmet needs level and inequality. An inverse association was observed between the ESCI and all-cause mortality in older adults (ß=-16.81, P=0.047) as well as mortality rate owing to noncommunicable diseases (ß=-17.58, P=0.041). The ESCI was inversely associated with mortality in older adults. This index could serve as a process evaluation indicator in assessing the progress toward UHC and healthy aging.

The Asymmetrical Fe-O-Se Bonds in Fe2O(SeO3)2 Boosting Bifunctional Oxygen Electrocatalytic Performance for Zinc-Air Battery.

Here Fe2O(SeO3)2/Fe3C@NC catalysts with high performance were fabricated for zinc-air batteries (ZABs). The experimental results confirmed that the existence of Fe-O-Se bonds in Fe2O(SeO3)2 crystal phase, and the Fe-O-Se bonds could obviously enhance ORR and OER catalytic performance of Fe2O(SeO3)2/Fe3C@NC. Density functional theoretical calculations (DFT) confirmed that the Fe2O(SeO3)2 in Fe2O(SeO3)2/Fe3C@NC had a higher d-band center of Fe atom and a lower p-orbital coupling degree with its own lattice O atom than Fe2O3, which leads to Fe site of Fe2O(SeO3)2 being more likely to adsorb external oxygen intermediates. The Fe-O-Se bonds in Fe2O(SeO3)2 results in the modification of coordination environment of Fe atoms and optimizes the adsorption energy of Fe site for oxygen intermediates. Compared with Fe2O3/Fe3C@NC, the Fe2O(SeO3)2/Fe3C@NC showed obvious enhancements of ORR/OER catalytic activities with a half-wave potential of 0.91 V for ORR in 0.1 M KOH electrolyte and a low overpotential of 345 mV for OER at 10 mA cm-2 in a 1.0 M KOH electrolyte. The peak power density and specific capacity of Fe2O(SeO3)2/Fe3C@NC-based ZABs are higher than those of Pt/C+RuO2-ZABs. The above results demonstrate that the asymmetrical Fe-O-Se bonds in Fe2O(SeO3)2 plays a key role in improving the bifunctional catalytic activities of ORR/OER for ZABs.

Silencing siRNA microneedle patches versus silicone sheets in reducing post-surgical scars: a randomized single-blinded intra-individually controlled clinical trial.

BACKGROUND: A common complication of wounds is exuberant growth of fibrotic scar tissue, which can lead to hypertrophic scars or keloids. There are currently no treatments with good evidence for preventing excessive scar tissue formation. In this study, we explored the use of microneedle patches containing siRNA inhibiting SPARC mRNA in reducing the volume of post-surgical scars. OBJECTIVE: We aim to compare the differences in the volume of post-surgical scars between daily application of siRNA-embedded dissolving microneedle patches and silicone sheets. The primary study outcome measure was the 3D volume of scar elevation.Our hypothesis was that scar formation in the half of the wound treated with siRNA microneedle patches will be lesser, as reflected by a smaller 3D volume, as compared to the half treated with silicone sheets. METHODS: This was an 8-week, single-blinded intra-individually controlled randomised trial in a tertiary dermatological centre. Patients with two-week-old post-operative wounds were recruited. Each half of the scar was randomly assigned to the microneedle patch or silicone sheet. Three-dimensional (3D) volumes were obtained from the scars via a high-resolution scanner at day 0, 30 and 60. RESULTS: At day 30, scars treated with the microneedle patches had a lower geometric mean volume of 0.79mm3 when compared to scars treated with silicone sheets, with a difference in mean percentage volume reduction of 10.70%.At day 60, scars treated with the microneedle patches had a statistically significant lower volume (8.88mm3) when compared to the side treated with silicone sheets (12.77mm3, p=0.005), with a difference in mean percentage reduction of 9.66%. Additionally, there was also a statistically significant difference between the percentage reduction in scar volume, compared to baseline, on the side treated with microneedle patches (mean=83.78%) compared to the side treated with silicone sheets (mean=74.11%). CONCLUSIONS: There was a significantly greater reduction in the volume of post-surgical scars on the side treated with microneedle patches compared to the side treated with silicone sheets. This demonstrates the use of transdermal gene silencing technology for scar inhibition and that siRNA microneedle patches can be an effective and safe modality in the reduction of scar tissue formation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12622000558729, https://www.anzctr.org.au.

Effectiveness of propofol in anesthetic management and cognitive function in schizophrenic patients undergoing convulsion-free modified electroconvulsive therapy.

OBJECTIVE: To investigate the effects of propofol on anesthetic effectiveness and cognitive functioning in schizophrenic patients undergoing convulsion-free modified electroconvulsive therapy (MECT). METHODS: A retrospective analysis was conducted on the clinical data of 80 schizophrenia patients treated with MECT at the Affiliated Brain Hospital of Guangzhou Medical University from January 2021 to December 2023. Patients were divided into a control group (39 patients) receiving etomidate and an observation group (41 patients) receiving a combination of etomidate and propofol for general anesthesia induction. Parameters compared between the groups included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), arterial oxygen saturation (SaO2), time to spontaneous respiration recovery, wakefulness time, cognitive function (assessed by the Wechsler Adult Intelligence Scale-Revised in China, WAIS-RC), symptom severity (measured by the Positive and Negative Syndrome Scale, PANSS), and adverse reactions. RESULTS: No significant differences were observed in SBP, DBP, HR, and SaO2 between the groups over time, nor was there any interaction between group and time on these parameters (all P>0.05). However, the observation group showed significantly shorter times to spontaneous respiration recovery and wakefulness (both P<0.05). Post-treatment, the observation group also had higher WAIS-RC scores and lower PANSS scores, along with a reduced total incidence of adverse reactions (all P<0.05). CONCLUSION: Propofol for the induction of general anesthesia in MECT, enhances clinical anesthetic outcomes, diminishes the impact on cognitive functions, and reduces the incidence of adverse reactions, thereby suggesting its high safety and efficacy.

[Diazotrophic abundance and community structure in rhizosphere soils of typical subtropical Cunninghamia lanceolata plantations]. / äºšçƒ­å¸¦å ¸åž‹æ‰æœ¨äººå·¥æž—æ ¹é™ åœŸå£¤å›ºæ°®èŒä¸°åº¦å’Œç¾¤è½ç»“æž„.

Rhizosphere is a vital area for substance exchange and energy transfer between roots and soil microorganisms. Therefore, diazotrophs in the rhizosphere play a pivotal role in facilitating plant nitrogen acquisition. We investigated the variability in the abundance and community structure of soil diazotrophs and the influencing factors across rhizosphere soils of Cunninghamia lanceolata in three locations: Baisha State-owned Forest Farm in Longyan City (BS), Sanming Forest Ecosystem and Global Change Research Station (SM), and Wuyishan National Forest Park in Nanping City (WYS), located in the western region of Fujian Province, quantified the diazotrophic abundance by using real-time quantitative PCR, and assessed the community structure by high-throughput sequencing. The results showed that soil pH, C:N ratio, and C:(N:P) stoichiometry in SM were notably lower compared to those in BS and WYS. In SM, the abundance of the nifH gene was 6.38×108 copies·g-1, significantly lower than 1.35×109 copies·g-1 in BS and 1.10×109 copies·g-1 in WYS. Additionally, α diversity index of diazotrophs was lower in SM compared to BS and WYS, while the community structure of diazotrophs in rhizosphere soils of BS and WYS was similar, which differed significantly from that in SM. The diazotrophic sequences in the three forest farms could be divided into 5 phylum, 8 classes, 15 orders, 23 families and 33 genera, with Proteobacteria, α-proteobacteria, and Bradyrhizobium as the dominant phylotypes. Soil pH, available phosphorus, NO3--N and C:(N:P) ratio were identified as significant factors influencing both the abundance and community structure of nifH genes, with soil pH performing the greatest. Taken together, there were spatial variations in the distribution of diazotrophic abundance and community structure in C. lanceolata rhizosphere soils, with soil pH as the primary driving factor.

Jianpi Huayu Prescription Prevents Atherosclerosis by Improving Inflammation and Reshaping the Intestinal Microbiota in ApoE-/- Mice.

This study established an LPS-induced RAW264.7 macrophage inflammatory injury model and an AS mouse vulnerable plaque model to observe the effect of JPHYP on macrophage inflammation, plaque formation, blood lipids, inflammation levels, intestinal flora and the influence of TLR4/MyD88/MAPK pathway, and explore the anti-AS effect and molecular mechanism of JPHYP, and detected 16S rRNA of mice intestinal microbes. The difference of intestinal flora in different groups of mice was compared to further explore the intervention effect of JPHYP and clarify the molecular biological mechanism of JPHYP in preventing and treating AS by regulating TLR4/MyD88/MAPK inflammatory signaling pathway and improving intestinal flora.

Selective Lithium Recovery from Spent Lithium Manganate Batteries Using Oxidative Stabilization Technique.

Using oxidizing compounds to handle the recycling of discarded lithium batteries has advanced significantly in recent years. One of the most prominent methods is the sintered electrode powder treatment using pre-used additives, with an aqueous solution of the oxidizing agent fueling highly selective lithium extraction and transition metals retention in the refractory material. Herein, phosphoric acid (H3PO4) was used as the exchanger and hydrogen ions provider, the oxidant (K2S2O8) activity was driven by heating, the raw material structure was deformed and adjusted by the oxidizing drive, and lithium was exhausted, while manganese was converted into manganese(III) phosphate hydrate and manganese dioxide insoluble material. The optimized conditions resulted in a lithium leaching rate of 94.16% and a separation factor of 95.74%, while the corresponding manganese leaching rate was limited to less than 5%. The X-ray diffraction, X-ray spectroscopy, scanning electron microscopy, and inductively coupled plasma mass spectrometry measurements were used to investigate the influence of oxidation driving force and lithium leaching. Finally, the lithium leach solution was continuously stirred with sodium carbonate in boiling water to obtain the precipitate, which was separated and washed several times to obtain high-purity lithium carbonate.

Effect of ethanol on the elasticities of double-stranded RNA and DNA revealed by magnetic tweezers and simulations.

The elasticities of double-stranded (ds) DNA and RNA, which are critical to their biological functions and applications in materials science, can be significantly modulated by solution conditions such as ions and temperature. However, there is still a lack of a comprehensive understanding of the role of solvents in the elasticities of dsRNA and dsDNA in a comparative way. In this work, we explored the effect of ethanol solvent on the elasticities of dsRNA and dsDNA by magnetic tweezers and all-atom molecular dynamics simulations. We found that the bending persistence lengths and contour lengths of dsRNA and dsDNA decrease monotonically with the increase in ethanol concentration. Furthermore, the addition of ethanol weakens the positive twist-stretch coupling of dsRNA, while promotes the negative twist-stretch coupling of dsDNA. Counter-intuitively, the lower dielectric environment of ethanol causes a significant re-distribution of counterions and enhanced ion neutralization, which overwhelms the enhanced repulsion along dsRNA/dsDNA, ultimately leading to the softening in bending for dsRNA and dsDNA. Moreover, for dsRNA, ethanol causes slight ion-clamping across the major groove, which weakens the major groove-mediated twist-stretch coupling, while for dsDNA, ethanol promotes the stretch-radius correlation due to enhanced ion binding and consequently enhances the helical radius-mediated twist-stretch coupling.

Association Between Sarcopenia, Clinical Outcomes, and Survival in Patients with Extensive-Stage Small Cell Lung Cancer Treated with First-Line Immunochemotherapy: A Prospective Cohort Study.

OBJECTIVE: To investigate the association between sarcopenia, short-term efficacy, and long-term survival in patients with extensive small-cell lung cancer (SCLC) treated with standard first-line immunochemotherapy. METHODS: A total of 63 patients initially diagnosed with extensive-stage small cell lung cancer were enrolled in the prospective study from December 1, 2020 to December 31, 2022. The clinical characteristics, body composition, blood test results, and image data were obtained before treatment. Patients were divided into sarcopenia and non-sarcopenia groups according to the diagnostic criteria of the Asian Sarcopenia Working Group 2019. The primary outcome was overall survival (OS) and comprehensive survival analyses were performed. Secondary outcomes included short-term efficacy and adverse events associated with first-line immunochemotherapy. RESULTS: The median age of the 63 patients enrolled in our study was 63.0 years (40-80 years). The incidence of sarcopenia was 19.0% (12/63) in patients with extensive SCLC. Compared with non-sarcopenia patients, extensive-stage SCLC patients with sarcopenia were significantly older (69.0 vs. 62.0, P = 0.017), and had lower body mass index (BMI) (20.29 vs. 24.27, P < 0.001), hand grip strength (HGS) (20.42 vs. 30.75, P < 0.001), and albumin (35.9 vs. 41.40, P < 0.001). The objective response rate after two cycles of standard first-line immunochemotherapy in the sarcopenia group was lower than in the non-sarcopenia group (30.0 vs. 78.9%, P = 0.012). There was no significant difference in chemotherapy-related hematological toxicity between the two groups. During a median follow-up of 15 months (3-33 months), patients with extensive SCLC had a median OS of 24 months, with 1-year survival of 75% and 2-year survival of 52%, respectively. Compared to non-sarcopenia patients, the median OS in the sarcopenia group was significantly shorter (9 vs. 24 months, P = 0.0014). Multivariate Cox analysis showed that sarcopenia was an independent risk factor for OS in patients with extensive SCLC (HR = 4.993, 95%CI = 1.106-22.538, P = 0.037). CONCLUSIONS: Patients with Extensive SCLC and sarcopenia had worse clinical outcomes and shorter OS. Sarcopenia is a prognostic factor affecting first-line treatment efficacy and long-term survival of patients with SCLC in the era of immunotherapy.

Diagnostic laparoscopy for pre-operative selection of patients with known peritoneal carcinomatosis for CRS-HIPEC: A systematic review and meta-analysis.

BACKGROUND: Preoperative selection of patients with Peritoneal Carcinomatosis (PC) for Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is challenging due to associated risks. Diagnostic laparoscopy (DL), an emerging alternative to conventional radiological imaging, has uncertain efficacy. This study aims to evaluate DL's diagnostic performance through a systematic review of available literature. METHODS: A comprehensive search of MEDLINE and SCOPUS databases from January 1987 to September 2023 identified studies investigating DL's diagnostic accuracy in selecting PC patients for CRS-HIPEC. Methodological bias assessment and analysis of performance metrics such as positive predictive value (PPV), sensitivity, specificity, and diagnostic odds ratio (DOR) were conducted. Subgroup analyses were performed for primary ovarian cancer studies, and false positive sites were identified. The summary receiver operating characteristic curve (sROC) was plotted to assess overall diagnostic efficacy, with meta-regression conducted to identify sources of heterogeneity across studies. RESULTS: This study included 25 studies comprising 3820 patients. Pooled PPV was 93.04 %, with a complication rate of 1.61 %. Pooled sensitivity was 98.26 % and pooled specificity was 83.67 %. The pooled DOR was 139.18, and sROC plot yielded an area under the curve of 0.96. Meta-regression found the ovarian subgroup as a strong source of heterogeneity. Subgroup analysis indicated similar findings in primary ovarian cancer studies, while false positives were commonly observed in the celiac axis, mesentery, ureters and para-aortic lymph nodes. CONCLUSION: DL demonstrates robust diagnostic accuracy in selecting PC patients for CRS-HIPEC, with potential benefits in patient outcomes and resource optimization. Further multicenter investigations are warranted to validate DL's efficacy across diverse primary cancer types.

The impact of vitamin E, vitamin B6, and niacin intake on cataract incidence based on NHANES 2005-2008 data.

Objective: This investigation aims to elucidate the correlations between dietary intakes of vitamin E, B6, and niacin and the incidence of cataracts, utilizing the comprehensive NHANES 2005-2008 dataset to affirm the prophylactic roles of these nutrients against cataract formation. Methods: Using data from the NHANES 2005-2008 cycles, this analysis concentrated on 7,247 subjects after exclusion based on incomplete dietary or cataract data. The identification of cataracts was determined through participants' self-reported ophthalmic surgical history. Nutritional intake was gauged using the automated multiple pass method, and the data were analyzed using logistic and quantile regression analyses to investigate the relationship between vitamin consumption and cataract prevalence. Results: Our analysis identified significant inverse associations between the intake of vitamins E, B6, and niacin and the risk of cataract development. Specifically, higher intakes of vitamin B6 (OR = 0.85, 95% CI = 0.76-0.96, p = 0.0073) and niacin (OR = 0.98, 95% CI = 0.97-1.00, p = 0.0067) in the top quartile were significantly associated with a reduced likelihood of cataract occurrence. Vitamin E intake showed a consistent reduction in cataract risk across different intake levels (OR = 0.96, 95% CI = 0.94-0.99, p = 0.0087), demonstrating a nonlinear inverse correlation. Conclusion: The outcomes indicate that elevated consumption of vitamin B6 and niacin, in conjunction with regular vitamin E intake, may have the potential to delay or prevent cataract genesis. These results suggest a novel nutritional strategy for cataract prevention and management, advocating that focused nutrient supplementation could be instrumental in preserving eye health and reducing the risk of cataracts. Further research is recommended to validate these findings and establish optimal dosages for maximum benefit.

Hub metastatic gene signature and risk score of breast cancer patients with small tumor sizes using WGCNA.

BACKGROUND: Breast cancer (BC) is the most common cancer in women and accounts for approximately 15% of all cancer deaths among women globally. The underlying mechanism of BC patients with small tumor size and developing distant metastasis (DM) remains elusive in clinical practices. METHODS: We integrated the gene expression of BCs from ten RNAseq datasets from Gene Expression Omnibus (GEO) database to create a genetic prediction model for distant metastasis-free survival (DMFS) in BC patients with small tumor sizes (≤ 2 cm) using weighted gene co-expression network (WGCNA) analysis and LASSO cox regression. RESULTS: ABHD11, DDX39A, G3BP2, GOLM1, IL1R1, MMP11, PIK3R1, SNRPB2, and VAV3 were hub metastatic genes identified by WGCNA and used to create a risk score using multivariable Cox regression. At the cut-point value of the median risk score, the high-risk score (≥ median risk score) group had a higher risk of DM than the low-risk score group in the training cohort [hazard ratio (HR) 4.51, p < 0.0001] and in the validation cohort (HR 5.48, p = 0.003). The nomogram prediction model of 3-, 5-, and 7-year DMFS shows good prediction results with C-indices of 0.72-0.76. The enriched pathways were immune regulation and cell-cell signaling. EGFR serves as the hub gene for the protein-protein interaction network of PIK3R1, IL1R1, MMP11, GOLM1, and VAV3. CONCLUSION: Prognostic gene signature was predictive of DMFS for BCs with small tumor sizes. The protein-protein interaction network of PIK3R1, IL1R1, MMP11, GOLM1, and VAV3 connected by EGFR merits further experiments for elucidating the underlying mechanisms.

APOE ε4-associated downregulation of the IL-7/IL-7R pathway in effector memory T cells: Implications for Alzheimer's disease.

INTRODUCTION: The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive. METHODS: The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). RESULTS: Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells. DISCUSSION: These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy. HIGHLIGHTS: The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.

Ruthenium Complex Suppresses Proliferation of Residual Hepatocellular Carcinoma after Incomplete Radiofrequency Ablation Therapy.

BACKGROUND: Radiofrequency ablation (RFA) is an effective therapy for hepatocellular carcinoma (HCC). However, incomplete radiofrequency ablation (IRFA) can promote the progression of residual cancer cells, which is a serious problem in the clinical application of RFA. Therefore, it is of great significance to explore the mechanism and countermeasures of the progression of residual tumors after IRFA. Our previous study confirmed that IRFA can activate the hypoxia/ autophagy pathway of residual tumors in mice and then induce the proliferation of residual tumor cells. Additionally, we found a metal ruthenium complex [Ru(bpy)2(ipad)](ClO4)2 (Ru, where bpy = 2,2'-bipyridine and ipad = 2-(anthracene-9,10-dione-2-yl)imidazo[4,5-f][1,10]phenanthroline) can effectively inhibit hypoxia-inducible factor (HIF-1α) and has good anti-tumor effect in a hypoxic environment; however, whether Ru could suppress the proliferation of residual tumor cells after IRFA is unknown. OBJECTIVE: This study intends to evaluate the effect of Ru in suppressing the proliferation of residual hepatocellular carcinoma after IRFA in a mice model. METHODS: The Hepa1-6 xenograft mouse model was established in C57BL/6 mice to simulate clinical IRFA. H&E staining was used to evaluate the biosafety of major organs in the treated mice. TUNEL assay was employed to assess the antitumor effect. Immunohistochemically and immunofluorescence staining was performed to detect the expression of HIF-1α and autophagy-related proteins. The ELISA assay was used to examine the cytokines of interferon-gamma (IFN-γ) and interleukin 10 (IL-10). RESULTS: Our findings revealed that the residual tumor relapsed via the HIF-1α/LC3B/P62 autophagy- related pathway after IRFA, while Ru could suppress this process. In addition, it was demonstrated that Ru could effectively activate the immune system of the mice and reverse the tumor immune suppression microenvironment after IRFA. CONCLUSION: The ruthenium complex Ru could suppress the proliferation of residual hepatocellular carcinoma cells after IRFA in the mice model. This study introduces a novel approach that combines the use of ruthenium complexes with IRFA, offering a potential solution to address the reoccurrence of residual liver cancer following IRFA in clinical settings.

Diagnostic laparoscopy with indocyanine green fluorescence test for the evaluation of intestinal perfusion in abdominal blunt injury: a case report.

BACKGROUND: The indocyanine green (ICG) fluorescence test has become a standard test in surgical procedures, facilitating the assessment of blood perfusion in real-time. While its utility in emergency surgeries for evaluating anastomotic blood supply is well-established, its application in trauma cases, especially those involving mesenteric hematoma, remains underexplored. Herein, we present a case to illustrate the efficacy of the ICG fluorescence test in such scenarios. CASE PRESENTATION: A 51-year-old man with uncontrolled hypertension suffered blunt abdominal trauma following a motor vehicle accident. We used the intra-operative ICG fluorescence test to chart the surgical plan for the patient. A combination of diagnostic laparoscopy with ICG fluorescence testing effectively excluded bowel ischemia, leading to the avoidance of intestinal resection and the need for a temporary ostomy. The patient resumed enteral nutrition. CONCLUSIONS: Our case underscores the efficacy of ICG fluorescence testing in assessing bowel viability and guiding surgical strategies in trauma patients with mesenteric hematoma. By facilitating real-time visualization of blood perfusion, ICG testing enables the adoption of conservative treatments in patients who would traditionally require more invasive surgical interventions, with minimal effect on operation time and cost.

Implementation of basic life support education for the lay public in China: barriers, enablers, and possible solutions.

Background: Education for the lay public in basic life support (BLS) is critical for increasing bystander cardiopulmonary resuscitation (CPR) rates and improving survival from out-of-hospital cardiac arrest (OHCA). Despite years of implementation, the BLS training rate in China has remained modest. The aim of this study was to investigate the factors influencing the implementation of BLS training programs in emergency medical service (EMS) centers in China and to identify specific barriers and enablers. Methods: Qualitative interviews were conducted with key informants from 40 EMS centers in Chinese cities. The participants included 11 directors/deputy directors, 24 training department leaders, and 5 senior trainers. The interview guide was based on the Exploration, Preparation, Implementation, Sustainment (EPIS) framework. Thematic content analysis was used to identify themes and patterns across the interviews. Results: We identified 16 factors influencing the implementation of BLS training programs encompassing the outer content, inner context, innovation and bridging factors. Some factors acted as either barriers or enablers at different EPIS stages. The main implementation barriers included limited external leadership, insufficient government investment, low public awareness, a shortage of trainers, an absence of incentives, an absence of authoritative courses and guidelines, a lack of qualification to issue certificates, limited academic involvement, and insufficient publicity. The main enablers were found to be supportive government leaders, strong public demand, adequate resources, program champions, available high-quality courses of high fitness within the local context, the involvement of diverse institutions, and effective publicity and promotion. Conclusion: Our findings emphasize the diversity of stakeholders, the complexity of implementation, and the need for localization and co-construction when conducting BLS training for lay public in city EMS centers. Improvements can be made at the national level, city level, and EMS institutional level to boost priority and awareness, promote legislation and policies, raise sustainable resources, and enhance the technology of BLS courses.

Antiferromagnetic phase transition in a 3D fermionic Hubbard model.

The fermionic Hubbard model (FHM)1 describes a wide range of physical phenomena resulting from strong electron-electron correlations, including conjectured mechanisms for unconventional superconductivity. Resolving its low-temperature physics is, however, challenging theoretically or numerically. Ultracold fermions in optical lattices2,3 provide a clean and well-controlled platform offering a path to simulate the FHM. Doping the antiferromagnetic ground state of a FHM simulator at half-filling is expected to yield various exotic phases, including stripe order4, pseudogap5, and d-wave superfluid6, offering valuable insights into high-temperature superconductivity7-9. Although the observation of antiferromagnetic correlations over short10 and extended distances11 has been obtained, the antiferromagnetic phase has yet to be realized as it requires sufficiently low temperatures in a large and uniform quantum simulator. Here we report the observation of the antiferromagnetic phase transition in a three-dimensional fermionic Hubbard system comprising lithium-6 atoms in a uniform optical lattice with approximately 800,000 sites. When the interaction strength, temperature and doping concentration are finely tuned to approach their respective critical values, a sharp increase in the spin structure factor is observed. These observations can be well described by a power-law divergence, with a critical exponent of 1.396 from the Heisenberg universality class12. At half-filling and with optimal interaction strength, the measured spin structure factor reaches 123(8), signifying the establishment of an antiferromagnetic phase. Our results provide opportunities for exploring the low-temperature phase diagram of the FHM.