Comparison of the connectivity of the posterior intralaminar thalamic nucleus and peripeduncular nucleus in rats and mice.

The posterior intralaminar thalamic nucleus (PIL) and peripeduncular nucleus (PP) are two adjoining structures located medioventral to the medial geniculate nucleus. The PIL-PP region plays important roles in auditory fear conditioning and in social, maternal and sexual behaviors. Previous studies often lumped the PIL and PP into single entity, and therefore it is not known if they have common and/or different brain-wide connections. In this study, we investigate brain-wide efferent and afferent projections of the PIL and PP using reliable anterograde and retrograde tracing methods. Both PIL and PP project strongly to lateral, medial and anterior basomedial amygdaloid nuclei, posteroventral striatum (putamen and external globus pallidus), amygdalostriatal transition area, zona incerta, superior and inferior colliculi, and the ectorhinal cortex. However, the PP rather than the PIL send stronger projections to the hypothalamic regions such as preoptic area/nucleus, anterior hypothalamic nucleus, and ventromedial nucleus of hypothalamus. As for the afferent projections, both PIL and PP receive multimodal information from auditory (inferior colliculus, superior olivary nucleus, nucleus of lateral lemniscus, and association auditory cortex), visual (superior colliculus and ectorhinal cortex), somatosensory (gracile and cuneate nuclei), motor (external globus pallidus), and limbic (central amygdaloid nucleus, hypothalamus, and insular cortex) structures. However, the PP rather than PIL receives strong projections from the visual related structures parabigeminal nucleus and ventral lateral geniculate nucleus. Additional results from Cre-dependent viral tracing in mice have also confirmed the main results in rats. Together, the findings in this study would provide new insights into the neural circuits and functional correlation of the PIL and PP.

Targeted delivery strategies: The interactions and applications of nanoparticles in liver diseases.

In recent years, nanoparticles have been broadly utilized in various drugs delivery formulations. Nanodelivery systems have shown promise in solving problems associated with the distribution of hydrophobic drugs and have promoted the accumulation of nanomedicines in the circulation or in organs. However, the injection dose of nanoparticles (NPs) is much greater than that needed by diseased tissues or organs. In other words, most of the NPs are localized off-target and do not reach the desired tissue or organs. With the rapid development of biodegradable and biosafety nanomaterials, the nanovectors represent assurance of safety. However, the off-target effects also induce concerns about the application of NPs, especially in the delivery of gene editing tools. Therefore, a complete understanding of the biological responses to NPs in the body will clearly guide the design of targeted delivery of NPs. The different properties of various nanodelivery systems may induce diverse interactions between carriers and organs. In this review, we describe the relationship between the liver, the most influenced organ of systemic administration of NPs, and targeted delivery nanoplatforms. Various transport vehicles have adopted multiple delivery strategies for the targeted delivery to the cells in the homeostasis liver and in diseased liver. Additionally, nanodelivery systems provide a novel strategy for treating incurable diseases. The appearance of a targeted delivery has profoundly improved the application of NPs to liver diseases.

The effect of outdoor activities on the medical expenditure of older people: multiple chain mediating effects of health benefits.

BACKGROUND: With the global aging population, attention to the health and medical issues of older adults is increasing. By analyzing the relationship between older people's participation in outdoor activities and medical expenditure, this study aims to provide a scientific basis for improving their quality of life and reducing the medical burden. METHODS: Data on outdoor activity participation, medical expenditures, and relevant variables were collected through questionnaires and databases. A multi-chain mediation effect model was established to analyze the impact of outdoor activities on the medical expenditure of older people, considering mediation effects and heterogeneity. RESULTS: Results revealed that increased participation in outdoor activities among older adults correlated with lower medical expenditures. Outdoor activities positively influenced their health by improving mental health, cognition, eating habits, and activities of daily living, resulting in reduced medical expenditures. Robustness tests confirmed the consistent effect of outdoor activities on older people's medical expenditure. CONCLUSION: These findings contribute to understanding the relationship between outdoor activities, health, and medical expenditure in older people, guiding policy formulation and interventions. Encouraging and supporting older adults in outdoor activities can enhance their quality of life and alleviate medical resource strain. The study's conclusions can also inform health promotion measures for other populations and serve as a basis for future research in this area.

Pellino1 orchestrates gut-kidney axis to perpetuate septic acute kidney injury through activation of STING pathway and NLRP3 inflammasome.

AIMS: Intestinal barrier dysfunction is the initial and propagable factor of sepsis in which acute kidney injury (AKI) has been considered as a common life-threatening complication. Our recent study identifies the regulatory role of Pellino1 in tubular death under inflammatory conditions in vitro. The objective of our current study is to explore the impact of Pellino1 on gut-kidney axis during septic AKI and uncover the molecular mechanism (s) underlying this process. MATERIALS AND METHODS: Immunohistochemistry (IHC) was conducted to evaluate Pellino1 and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) levels in renal biopsies from critically ill patients with a clinical diagnosis of sepsis. Functional and mechanistic studies were characterized in septic models of the Peli-knockout (Peli1-/-) mice by histopathological staining, enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence, biochemical detection, CRISPR/Cas9-mediated gene editing and intestinal organoid. KEY FINDINGS: Pellino1, together with NLRP3, are highly expressed in renal biopsies from critically ill patients diagnosed with sepsis and kidney tissues of septic mice. The Peli1-/- mice with sepsis become less prone to develop AKI and have markedly compromised NLRP3 activation in kidney. Loss of Peli1 endows septic mice refractory to intestinal inflammation, barrier permeability and enterocyte apoptosis that requires stimulator of interferons genes (STING) pathway. Administration of STING agonist DMXAA deteriorates AKI and mortality of septic Peli1-/- mice in the presence of kidney-specific NLRP3 reconstitution. SIGNIFICANCE: Our studies suggest that Pellino1 has a principal role in orchestrating gut homeostasis towards renal pathophysiology, thus providing a potential therapeutic target for septic AKI.

Lactic acid bacteria reduce bacterial diarrhea in rabbits via enhancing immune function and restoring intestinal microbiota homeostasis.

BACKGROUND: Numerous previous reports have demonstrated the efficacy of Lactic acid bacteria (LAB) in promoting growth and preventing disease in animals. In this study, Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 were isolated from the feces of healthy rabbits, and both strains showed good probiotic properties in vitro. Two strains (108CFU/ml/kg/day) were fed to weaned rabbits for 21 days, after which specific bacterial infection was induced to investigate the effects of the strains on bacterial diarrhea in the rabbits. RESULTS: Our data showed that Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 interventions reduced the incidence of diarrhea and systemic inflammatory response, alleviated intestinal damage and increased antibody levels in animals. In addition, Enterococcus faecium ZJUIDS-R1 restored the flora abundance of Ruminococcaceae1. Ligilactobaciiius animalis ZJUIDS-R2 up-regulated the flora abundance of Adlercreutzia and Candidatus Saccharimonas. Both down-regulated the flora abundance of Shuttleworthia and Barnesiella to restore intestinal flora balance, thereby increasing intestinal short-chain fatty acid content. CONCLUSIONS: These findings suggest that Enterococcus faecium ZJUIDS-R1 and Ligilactobaciiius animalis ZJUIDS-R2 were able to improve intestinal immunity, produce organic acids and regulate the balance of intestinal flora to enhance disease resistance and alleviate diarrhea-related diseases in weanling rabbits.

Quantitative evaluation and mechanism analysis of soil chemical factors affecting rice yield in saline-sodic paddy fields.

Salinization and sodication have become an important abiotic stress affecting soil fertility and crop production in the western of the Songnen Plain in Northeast China. And rice cultivation is considered as one of the most effective biological methods to reclaim saline-sodic soils and ensure food security. However, it is difficult to select the optimal measures to regulate rice growth for increasing yield, because the independent and comprehensive influences of the soil limitation factors on rice yield are not quantitatively evaluated. In this study, the hierarchical partitioning (HP) and the structural equation model (SEM) were used to quantitatively evaluate the influences of salinization parameters, salt ion concentrations and soil nutrients to identify the dominant limitation factors and obstacle mechanism for rice yield. The results showed that soil pH was the key index in salinization parameters, [CO32- + HCO3-] was the key index in salt ion concentrations and available nitrogen (AN) was the key index in soil nutrients to impact rice yield, which independent influences reached 53.7 %, 45.4 % (negative) and 53.2 % (positive), respectively. Soil pH was determined by [CO32- + HCO3-], and the negative effect of alkali stress on rice yield mainly caused by [CO32- + HCO3-] was greater than that of salt stress mainly caused by [Na+] in saline-sodic paddy fields. Among the soil chemical factors, soil pH and AN were the most important explanatory variables of rice yield in saline-sodic paddy fields, which standardized total effects were - 0.32 and 0.40, respectively. Furthermore, the AN showed a more significant negative correlation with soil pH and a higher yield-increasing potential in severe saline-sodic soils (9 ≤ pH < 10) than that in moderate saline-sodic soils (8 ≤ pH < 9). Therefore, decreasing [CO32- + HCO3-] and increasing the content of AN are key to improve rice yield in saline-sodic paddy fields.

Optimization of tight gas reservoir fracturing parameters via gradient boosting regression modeling.

In China, the exploitation of most unconventional oil and gas reservoirs is dependent on hydraulic fracturing, which is a key method employed when developing tight gas formations. Numerous scholars and field engineers, both domestically and internationally, have conducted extensive numerical simulations and physical experiments to study crack propagation and predict post-fracturing productivity in hydraulic fracturing. Although some progress has been reported in this regard, it is difficult to accurately predict the well productivity using mechanistic models owing to the vertical multilayered development of tight gas reservoirs. In this study, vertical fractured wells in a block of Sulige gas field were examined. The block relied on hydraulic fracturing to produce tight gases. However, as development progressed, the available reservoir environment deteriorated, large differences emerged between wells after fracturing, and the fracturing results did not meet the expectations. In this study, geological, construction, and generation data for this block that had been collected since 2007 were analyzed. After applying multiple machine-learning methods to filter outliers and fill in missing values, k-means clustering, classification enhancement, extreme gradient enhancement, and LightGBM algorithms were used to establish a regression model. The analysis results revealed that the regression accuracy of the cluster test set was as high as 70% and that the LightGBM model had the best regression effect among the 227 stripper wells in the block. After optimizing the fracturing construction parameters (fracturing fluid volume, proppant volume, liquid-nitrogen volume, and pumping rate), the average fracturing fluid and liquid-nitrogen volumes per well decreased, whereas the unit reservoir proppant and liquid-nitrogen volumes increased. The results also revealed that 182 wells showed an improved initial production capacity during fracturing. The average gas production index per meter increased by 22.04%. This approach enabled rapid and efficient production forecasting and construction optimization. Moreover, this represents a novel fracture design method that is applicable to onsite engineers in tight gas production fields in the Ordos region.

Isolation of two peptaibols with potent antimicrobial and cytotoxic activities from the mangrove endophytic fungus Trichoderma lentiforme ML-P8-2.

Trichorzin PA is a family of 18-residue peptaibols with linear and flexible peptide chains. The three-dimensional structures and biological activities of trichorzin PA peptaibols are largely uncharacterised. In this work, two previously identified peptaibols, trichorzin PA VI (1) and II (2), were isolated from Trichoderma lentiforme ML-P8-2. While for the first time, we report here the X-ray crystallographic structure of 1, antimicrobial activities against a panel of common pathogenic bacteria and fungi, and cytotoxicities of 1 and 2. In bioassays, 1 and 2 exhibited strong antimicrobial activities against the seven tested microbes, with MIC values in the range of 0.19-6.25 µM. Additionally, 1 and 2 displayed potent cytotoxicities against five human cancer cell lines, with IC50 values in the range of 0.01 ± 0.02-2.75 ± 0.17 µM. The bioassay results were generally better than those reported for other 18-residue peptaibols, including other trichorzin PA members.

Spontaneous regression of a giant uterine leiomyoma after delivery: a case report and literature review.

BACKGROUND: Uterine leiomyomas are hormone-dependent benign tumors and often begin to shrink after menopause due to the reduction in ovarian steroids. The influence of pregnancy on uterine leiomyomas size remains unclear. Here, we present a case of spontaneous regression of a giant uterine leiomyoma after delivery. CASE PRESENTATION: A 40-year-old woman presented with multiple uterine leiomyomas, one of which is a giant uterine leiomyomas (approximately 8 cm in diameter) that gradually shrinked after delivery. At over two months postpartum, the large myometrial leiomyoma had transformed into a submucosal leiomyoma, and over 3 years postpartum, both the submucosal leiomyoma and multiple intramural leiomyomas completely regressed. CONCLUSION: Spontaneous regression of a giant uterine leiomyom is rare after delivery. Considering uterine leiomyoma regression until over 3 year postpartum,we need to observe the regression of uterine fibroid for a longer time postpartum in the absence of fibroid related complications. In addition, it will provide new insights for treatment options of uterine leiomyomas in the future.

Sewage sludge-derived nutrients and biostimulants stimulate rice leaf photosynthesis and root metabolism to enhance carbohydrate, nitrogen and antioxidants accumulation.

The production of high quality liquid nitrogen fertilizer with both nutrient comprehensive and biostimulant properties by alkaline thermal hydrolysis of sewage sludge has shown great potential in agricultural production. However, little is known about the effects of sewage sludge-derived nutrients, and biostimulants (SS-NB) on leaf photosynthesis and root growth in rice. Phenotypic, metabolic and microbial analyses were used to reveal the mechanism of SS-NB on rice. Compared to NF treatment, phenotypic parameters (fresh/dry weight, soluble sugar, amino acid, protein) were increased by SS-NB in rice. SS-NB can enhance the photosynthesis of rice leaves by improving the photoconversion efficiency, chlorophyll content, ATP synthase activity, Rubisco and NADPH production. Meanwhile, SS-NB also increased antioxidant capacity (SOD, POD, CAT and proline) in rice leaf and root tissues. Metabolomics revealed that SS-NB application increased the expression levels of metabolites in root and leaf tissues, including carbohydrate, nitrogen and sulfur metabolism, amino acid metabolism, antioxidants, and phytohormone. Most importantly, the regulation of metabolites in rice root tissues is more sensitive than in leaf tissues, especially to the higher levels of antioxidants and phytohormones (IAA and GA) in rice root tissues. Furthermore, SS-NB increased the abundance of photosynthetic autotrophic, organic acids-degrading and denitrifying functional bacteria in rice roots and recruited plant growth-promoting bacteria (Azospirillum and norank_f_JG30-KF-CM45), while the NF treatment group resulted in an imbalance of the microbial community, leading to the dominance of pathogenic bacteria. The results showed that SS-NB had great application potential in crop growth and stress resistance improvement.

Formation processes of groundwater in a non-ferrous metal mining city of China: Insights from hydrochemical and strontium isotope analyses.

Tongling is a significant non-ferrous metal mining city in China, which produces waste that negatively impacts the area's water environment. It is essential to comprehend the hydrochemical properties and formation processes of groundwater to safeguard and utilize it efficiently. We explored major ions, strontium, and its isotopes in water and river-bottom samples from the northern (i.e., A-A' section) and southern (i.e., B-B' section) areas. The hydrochemical facies show the mining activities have a greater impact on surface water than on groundwater. Groundwater hydrochemical formation results from several factors, with water-rock interaction and ion exchange being primary. Additionally, the dissolution of calcite, dolomite, and feldspar, oxidation of pyrite, and hydrolysis of carbonate minerals also impact the formation of groundwater chemistry. Our analysis of strontium and its isotopes indicates that carbonate dissolution primarily occurred in the recharge area; the runoff from the recharge to the discharge area results in the dissolution of certain silicate rocks; calcite dissolution sources account for > 70% contribution in both surface water and groundwater water-rock interactions, whereas silicate rock dissolution sources and dolomite dissolution sources account for < 30%. Due to changed order of dissolved carbonate and silicate minerals during groundwater flow, the distribution of strontium and its isotopes in the A-A' section is opposite to that in the B-B' section. The findings provide a basis for developing, utilizing, managing, and protecting groundwater resources, especially in similar mining areas.

N-methyl pyrrolidone manufacturing wastewater as the electron donor for denitrification: From bench to pilot scale.

Actual wastewater generated from N-methylpyrrolidone (NMP) manufacture was used as electron donor for tertiary denitrification. The organic components of NMP wastewater were mainly NMP and monomethylamine (CH3NH2), and their biodegradation released ammonium that was nitrified to nitrate that also had to be denitrified. Bench-scale experiments documented that alternating denitrification and nitrification realized effective total­nitrogen removal. Ammonium released from NMP was nitrified in the aerobic reactor and then denitrified when actual NMP wastewater was used as the electron donor for endogenous and exogenous nitrate. Whereas TN and NMP removals occurred in the denitrification step, dissolved organic carbon (DOC) and CH3NH2 removals occurred in the denitrification and nitrification stages. The genera Thauera and Paracoccus were important for NMP biodegradation and denitrification in the denitrification reactor; in the nitrification stage, Amaricoccus and Sphingobium played key roles for biodegrading intermediates of NMP, while Nitrospira was responsible for NH4+ oxidation to NO3-. Pilot-scale demonstration was achieved in a two-stage vertical baffled bioreactor (VBBR) in which total­nitrogen removal was realized sequential anoxic-oxic treatment without biomass recycle. Although the bench-scale reactors and the VBBR had different configurations, both effectively removed total nitrogen through the same mechanisms. Thus, an N-containing organic compound in an industrial wastewater could be used to drive total-N removal in a tertiary-treatment scenario.

Dapoxetine, a Selective Serotonin Reuptake Inhibitor, Suppresses Zika Virus Infection In Vitro.

Zika virus (ZIKV) belongs to the Flavivirus genus of the Flaviviridae family, and is a pathogen posing a significant threat to human health. Currently, there is a lack of internationally approved antiviral drugs for the treatment of ZIKV infection, and symptomatic management remains the primary clinical approach. Consequently, the exploration of safe and effective anti-ZIKV drugs has emerged as a paramount imperative in ZIKV control efforts. In this study, we performed a screening of a compound library consisting of 1789 FDA-approved drugs to identify potential agents with anti-ZIKV activity. We have identified dapoxetine, an orally administered selective serotonin reuptake inhibitor (SSRI) commonly employed for the clinical management of premature ejaculation (PE), as a potential inhibitor of ZIKV RNA-dependent RNA polymerase (RdRp). Consequently, we conducted surface plasmon resonance (SPR) analysis to validate the specific binding of dapoxetine to ZIKV RdRp, and further evaluated its inhibitory effect on ZIKV RdRp synthesis using the ZIKV Gluc reporter gene assay. Furthermore, we substantiated the efficacy of dapoxetine in suppressing intracellular replication of ZIKV, thereby demonstrating a concentration-dependent antiviral effect (EC50 values ranging from 4.20 µM to 12.6 µM) and negligible cytotoxicity (CC50 > 50 µM) across diverse cell lines. Moreover, cell fluorescence staining and Western blotting assays revealed that dapoxetine effectively reduced the expression of ZIKV proteins. Collectively, our findings suggest that dapoxetine exhibits anti-ZIKV effects by inhibiting ZIKV RdRp activity, positioning it as a potential candidate for clinical therapeutic intervention against ZIKV infection.

Ascomylactam C Induces an Immunogenic Cell Death Signature via Mitochondria-Associated ER Stress in Lung Cancer and Melanoma.

Ascomylactam C (AsC) is a new 13-membered-ring macrocyclic alkaloid, which was first isolated and identified in 2019 from the secondary metabolites of the mangrove endophytic fungus Didymella sp. CYSK-4 in the South China Sea. AsC has been found to have a broad-spectrum cytotoxic activity. However, the antitumor effects in vivo and mechanisms of AsC remain unclear. The aim of this study was to describe the effects of AsC on lung cancer and melanoma cells and to explore the antitumor molecular mechanism of AsC. In vitro, we used plate colony formation experiments and demonstrated the ability of AsC to inhibit low-density tumor growth. An Annexin V/PI cell apoptosis detection experiment revealed that AsC induced tumor cell apoptosis. In vivo, AsC suppressed the tumor growth of LLC and B16F10 allograft significantly in mice, and promoted the infiltration of CD4+ T and CD8+ T cells in tumor tissues. Mechanistically, by analyses of Western blotting, immunofluorescence and ELISA analysis, we found that AsC increased ROS formation, induced endoplasmic reticulum (ER) stress, activated the protein kinase RNA-like ER kinase (PERK)/eukaryotic translation initiation factor (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway, and induced immunogenic cell death (ICD) of tumor cells. Our results suggest that AsC may be a potentially promising antitumor drug candidate.

The impact of confirmed cases of COVID-19 on residents' traditional Chinese medicine health literacy: A survey from Gansu Province of China.

Since the outbreak of the new crown epidemic in China in early 2020, the number of confirmed cases of COVID-19 has continued to increase, and the Chinese government's policy of "static management" in the first round of the epidemic may affect the health behavior adjustment of Chinese residents. Using survey data on the TCM health literacy of 4016 residents in China (Gansu Province), a causal inference approach was used to explore the impact of the emergence of confirmed cases of COVID-19 on residents' TCM health literacy. We found that the emergence of confirmed cases can increase by 3.5%-7.0% in residents' TCM health literacy. Among them, the TCM health literacy of uneducated residents has not improved significantly, and the residents with secondary education have increased significantly by 8%. For those with higher education, the number of residents increased significantly by 6%. At the same time, the emergence of confirmed cases will increase the residents' practical TCM health literacy and decrease theoretical TCM health literacy. Through heterogeneity analysis, we explored the impact mechanism of confirmed cases on residents' TCM health literacy. We believe that the emergence of confirmed cases will make residents more inclined to participate in TCM-free clinics, theme activities, and other ways to acquire TCM knowledge.

Limited energy migration and circumscribed multiphonon relaxation produced non-concentration quenching in a novel dazzling red-emitting phosphor.

White LED applications are still constrained by extremely efficient narrow band red emitting phosphors. Meanwhile, the concentration quenching induced by energy migration is the main reason that limits the emission intensity of a red emitting phosphor. Therefore, developing a novel red emitting material with energy migration limitations seems necessary. Here, we proposed and realized the non-concentration quenching doping of Eu3+ ions in a Sr9Y2-2xW4O24:xEu3+ (0 ≤ x ≤ 1.0) phosphor for the first time by means of host preferential selection. By clearly investigating the crystal structure and luminescence kinetics, the long-distance between the nearby Eu3+ ions and the low phonon energy are the main reasons that suppress the energy migration and the cross-relaxation among Eu3+ ions. These advantages result in a high internal (90.47%) and external quantum efficiency (42.1%) of Sr9Eu2W4O24. With the help of the Judd-Ofelt theory and the large value of oscillator strength Ω2, Eu3+ ions are verified to occupy the non-symmetric lattice site with high color purity (94.4%). In addition, only 5.2% emission intensity loss at 140 °C can guarantee its application in LED devices. Moreover, the SYWO:Eu3+ phosphor has high thermal tolerance, high color stability, excellent moisture resistance and superior physical/chemical stability, and thus has broad practical spectral application prospects. The prepared WLED shows superior performance, and the calculated NTSC values are as high as 101.8% and 104.7%, respectively. For comparison, the optical performances of the Sr9Y2W4O24:Eu3+ phosphor outperform those of the standard commercial red phosphors, Y2O3:Eu3+ and Y2O2S:Eu3+, and almost match that of K2MnF6. These results may pave the way for fresh approaches to the study of high-performance Eu3+-activated phosphors.

Comprehensive comparative analysis of the prognostic impact of systemic inflammation biomarkers for patients underwent cardiac surgery.

Background: Inflammation plays an integral role in the development of cardiovascular disease, and few studies have identified different biomarkers to predict the prognosis of cardiac surgery. But there is a lack of reliable and valid evidence to determine the optimal systemic inflammatory biomarkers to predict prognosis. Methods: From December 2015 and March 2021, we collected 10 systemic inflammation biomarkers among 820 patients who underwent cardiac surgery. Time-dependent receiver operating characteristic curves (ROC) curve at different time points and C-index was compared at different time points. Kaplan-Meier method was performed to analyze overall survival (OS). Cox proportional hazard regression analyses were used to assess independent risk factors for OS. A random internal validation was conducted to confirm the effectiveness of the biomarkers. Results: The area under the ROC of lymphocyte-to-C-reactive protein ratio (LCR) was 0.655, 0.620 and 0.613 at 1-, 2- and 3-year respectively, and C-index of LCR for OS after cardiac surgery was 0.611, suggesting that LCR may serve as a favorable indicator for predicting the prognosis of cardiac surgery. Patients with low LCR had a higher risk of postoperative complications. Besides, Cox proportional hazard regression analyses indicated that LCR was considered as an independent risk factor of OS after cardiac surgery. Conclusion: LCR shows promise as a noteworthy representative among the systemic inflammation biomarkers in predicting the prognosis of cardiac surgery. Screening for low LCR levels may help surgeons identify high-risk patients and guide perioperative management strategies.

Research progresses on the effects of heavy metals on the circadian clock system.

Environmental pollution with heavy metals is widespread, thus increasing attention has been paid to their toxic effects. Recent studies have suggested that heavy metals may influence the expression of circadian clock genes. Almost all organs and tissues exhibit circadian rhythms. The normal circadian rhythm of an organism is maintained by the central and peripheral circadian clock. Thus, circadian rhythm disorders perturb normal physiological processes. Here, we review the effects of heavy metals, including manganese, copper, cadmium, and lead, on four core circadian clock genes, i.e., ARNTL, CLOCK, PER, and CRY genes.

Barnacle-Inspired Wet Tissue Adhesive Hydrogels with Inherent Antibacterial Properties for Infected Wound Treatment.

Currently, antibiotics are the most common treatment for bacterial infections in clinical practice. However, with the abuse of antibiotics and the emergence of drug-resistant bacteria, the use of antibiotics has faced an unprecedented challenge. It is imminent to develop nonantibiotic antimicrobial agents. Based on the cation-π structure of barnacle cement protein, a polyphosphazene-based polymer poly[(N,N-dimethylethylenediamine)-g-(N,N,N,N-dimethylaminoethyl p-ammonium bromide (ammonium bromide)-g-(N,N,N,N-dimethylaminoethyl acetate ethylammonium bromide)] (PZBA) with potential adhesion and inherent antibacterial properties was synthesized, and a series of injectable antibacterial adhesive hydrogels (PZBA-PVA) were prepared by cross-linking with poly(vinyl alcohol) (PVA). PZBA-PVA hydrogels showed good biocompatibility, and the antibacterial rate of the best-performed hydrogel reached 99.81 ± 0.04% and 98.80 ± 2.16% against Staphylococcus aureus and Escherichia coli within 0.5 h in vitro, respectively. In the infected wound model, the healing rate of the PZBA-PVA-treated group was significantly higher than that of the Tegaderm film group due to the fact that the hydrogel suppressed inflammatory responses and modulated the infiltration of immune cells. Moreover, the wound healing mechanism of the PZBA-PVA hydrogel was further evaluated by real-time polymerase chain reaction and total RNA sequencing. The results indicated that the process of hemostasis and tissue development was prompted and the inflammatory and immune responses were suppressed to accelerate wound healing. Overall, the PZBA-PVA hydrogel is shown to have the potential for infected wound healing application.

Peptidase inhibitor (PI16) impairs bladder cancer metastasis by inhibiting NF-κB activation via disrupting multiple-site ubiquitination of NEMO.

BACKGROUND: Bladder cancer (BLCA) is a malignancy that frequently metastasizes and leads to poor patient prognosis. It is essential to understand the molecular mechanisms underlying the progression and metastasis of BLCA and identify potential biomarkers. METHODS: The expression of peptidase inhibitor 16 (PI16) was analysed using quantitative PCR, immunoblotting and immunohistochemistry assays. The functional roles of PI16 were evaluated using wound healing, transwell, and human umbilical vein endothelial cell tube formation assays, as well as in vivo tumour models. The effects of PI16 on nuclear factor κB (NF-κB) signalling activation were examined using luciferase reporter gene systems, immunoblotting and immunofluorescence assays. Co-immunoprecipitation was used to investigate the interaction of PI16 with annexin-A1 (ANXA1) and NEMO. RESULTS: PI16 expression was downregulated in bladder cancer tissues, and lower PI16 levels correlated with disease progression and poor survival in patients with BLCA. Overexpressing PI16 inhibited BLCA cell growth, motility, invasion and angiogenesis in vitro and in vivo, while silencing PI16 had the opposite effects. Mechanistically, PI16 inhibited the activation of the NF-κB pathway by interacting with ANXA1, which inhibited K63 and M1 ubiquitination of NEMO. CONCLUSIONS: These results indicate that PI16 functions as a tumour suppressor in BLCA by inhibiting tumour growth and metastasis. Additionally, PI16 may serve as a potential biomarker for metastatic BLCA.