Integrating respiratory microbiome and host immune response through machine learning for respiratory tract infection diagnosis.

At present, the diagnosis of lower respiratory tract infections (LRTIs) is difficult, and there is an urgent need for better diagnostic methods. This study enrolled 136 patients from 2020 to 2021 and collected bronchoalveolar lavage fluid (BALF) specimens. We used metatranscriptome to analyze the lower respiratory tract microbiome (LRTM) and host immune response. The diversity of the LRTM in LRTIs significantly decreased, manifested by a decrease in the abundance of normal microbiota and an increase in the abundance of opportunistic pathogens. The upregulated differentially expressed genes (DEGs) in the LRTIs group were mainly enriched in infection immune response-related pathways. Klebsiella pneumoniae had the most significant increase in abundance in LRTIs, which was strongly correlated with host infection or inflammation genes TNFRSF1B, CSF3R, and IL6R. We combined LRTM and host transcriptome data to construct a machine-learning model with 12 screened features to discriminate LRTIs and non-LRTIs. The results showed that the model trained by Random Forest in the validate set had the best performance (ROC AUC: 0.937, 95% CI: 0.832-1). The independent external dataset showed an accuracy of 76.5% for this model. This study suggests that the model integrating LRTM and host transcriptome data can be an effective tool for LRTIs diagnosis.

Effect of skeletal muscle index on post-embolization syndrome of hepatocellular carcinoma after transarterial chemoembolization.

BACKGROUND: Skeletal muscle index (SMI) is a commonly used research method for evaluating muscle mass.However, its impact on post-embolization syndrome(PES) of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is unclear.Our objective was to determine the effect of SMI on PES after TACE in patients with HCC. METHODS: We conducted a retrospective analysis of patients who received TACE treatment for HCC at our hospital from 2015 to 2020. The subjects were divided into two groups according to the presence or absence of PES after TACE, and their clinical characteristics were compared.SMI was measured and calculated by cross-sectionally at the level of the third lumbar vertebra based on computed tomography (CT). According to the cutoff value, the patients were classified into either low or high SMI group.Potential risk factors for PES were assessed using univariate and multivariable Cox proportional risk models. RESULTS: A total of 110 people were included in this study, from which including 82 patients experienced PES. Serum albumin was significantly lower in the PES group compared to the non-PES group.The frequency of HCC with a maximum diameter > 3 cm and low SMI in the PES group was significantly higher than in patients without PES. Cox multivariate analysis identified that the maximum diameter of HCC > 3 cm and low SMI were independent predictors of PES after TACE. CONCLUSIONS: Low SMI is an independent predictor of PES in HCC patients after TACE treatment, making preoperative CT assessment of skeletal muscle mass is a simple and effective tool for predicting PES.

Glucopyranosyloxybenzyl succinates and their biological activities.

Over the past decades, great efforts have been made to explore the glucopyranosyloxybenzyl succinates from Orchidaceae. At the same time, some of those compounds with new structures have led to new findings of their biological functions. The structures, classifications, distributions and bioactivities of glucopyranosyloxybenzyl succinates have been summarized in this review.

Evaluation of the Bioavailability of Iodine and Arsenic in Raw and Cooked Saccharina japonica Based on Simulated Digestion/Caco-2 Cell Model.

Kelp is a traditional healthy food due to its high nutritional content; however, its relatively high contents of iodine and arsenic have raised concerns about its edible safety. This study explored the effects of different cooking treatments on the contents of iodine and arsenic in kelp, evaluated the bioaccessibility and bioavailability of iodine and arsenic in kelp using in vitro digestion, and compared the differences in the transport characteristics of iodine in kelp and KIO3 using a Caco-2 monolayer cell transport model. The results show that the content of target elements that reached systemic circulation could be reduced by cooking and gastrointestinal digestion. The highest reductions in iodine and arsenic were 94.4% and 74.7%, respectively, which were achieved by boiling for 10 min. The bioaccessibility and bioavailability of iodine and arsenic were significantly improved by a cooking treatment. However, the contents of iodine and arsenic decreased significantly, with the bioaccessibility of iodine reducing from 3188.2 µg/L to 317.0 µg/L and that of arsenic reducing from 32.5 µg/L to 18.1 µg/L in the gastric phase after boiling. The findings also show that the efficiency of iodine transport in kelp and KIO3 was positively correlated with the transport time and negatively correlated with the concentration of iodine. With the increase in the iodine concentration, the rate of iodine transport in kelp decreased from 63.93% to 3.14%, but that of KIO3 was stable at around 35%, which indicates that the absorption efficiency of iodine from kelp was limited, even when too much kelp was ingested. In conclusion, the edible safety of kelp is significantly improved after cooking. The risk of excessive iodine and arsenic intake caused by consuming kelp is extremely low, and as an effective iodine supplement source, kelp has higher edible safety compared with KIO3. This study clarifies the safety of algae based on iodine and arsenic contents and also provides a basis for the formulation of food safety standards.

Cancer cell-intrinsic biosynthesis of itaconate promotes tumor immunogenicity.

The Krebs cycle byproduct itaconate has recently emerged as an important metabolite regulating macrophage immune functions, but its role in tumor cells remains unknown. Here, we show that increased tumor-intrinsic cis-aconitate decarboxylase (ACOD1 or CAD, encoded by immune-responsive gene 1, Irg1) expression and itaconate production promote tumor immunogenicity and anti-tumor immune responses. Furthermore, we identify thimerosal, a vaccine preservative, as a specific inducer of IRG1 expression in tumor cells but not in macrophages, thereby enhancing tumor immunogenicity. Mechanistically, thimerosal induces itaconate production through a ROS-RIPK3-IRF1 signaling axis in tumor cells. Further, increased IRG1/itaconate upregulates antigen presentation-related gene expression via promoting TFEB nuclear translocation. Intratumoral injection of thimerosal induced itaconate production, activated the tumor immune microenvironment, and inhibited tumor growth in a T cell-dependent manner. Importantly, IRG1 deficiency markedly impaired tumor response to thimerosal treatment. Furthermore, itaconate induction by thimerosal potentiates the anti-tumor efficacy of adoptive T-cell therapy and anti-PD1 therapy in a mouse lymphoma model. Hence, our findings identify a new role for tumor intrinsic IRG1/itaconate in promoting tumor immunogenicity and provide a translational means to increase immunotherapy efficacy.

Computationally-Assisted Discovery and Assignment of a New Class of 6/6/5/5 Fused-Ring Diterpene Acting as Pregnane X Receptor Ligands from Isodon serra.

We report here the orchestration of molecular ion networking (MoIN) and a set of computationally assisted structural elucidation approaches in the discovery and assignment of a new class of rearranged 4,5-seco-abietane diterpenoids including serra A (1), which possesses an unusual 6/6/5/5 fused-ring skeleton system, together with two previously unreported diterpenoids serras B-C (2-3) and five known compounds were isolated from Isodon serra (I. serra). The structures were elucidated by spectroscopic analysis in conjunction with computationally assisted structure elucidation tools. In silico, serras A-C (1-3) bind well to PXR, suggesting their potential role in reducing inflammation. The results of serra A (1) with hPXR demonstrated agonist activity with an EC50 value of 15 µM. Serra A (1), graciliflorin F (4), gerardianin C (5), 11,12,15-trihydroxy-8,11,13-abietatrien-7-one (6), rabdosin D (7), and 15-hydroxysalprionin (8) exhibited promising anti-inflammatory activities in lipopolysaccharide (LPS)-induced RAW 267.4 cells, and their inhibition rates on NO production were more than 65% at 10 µM.

Investigating the modulatory effects of lactoferrin on depressed rats through 16S rDNA gene sequencing and LC-MS metabolomics analysis.

Lactoferrin is a natural multifunctional glycoprotein with potential antidepressant-like effects. However, the mechanism of its antidepressant effect has not been explored from the perspective of gut flora metabolism. Therefore, we employed both 16S rDNA gene sequencing and LC-MS metabolomics analysis to investigate the regulatory effects and mechanisms of lactoferrin in a rat model of depression. After one week of acclimatization, twenty-four 7-week-old male Sprague-Dawley rats were randomly and equally assigned into three groups: the control group, the model group, and the lactoferrin intervention group. The control group rats were housed under standard conditions, while the rats in the model and lactoferrin intervention groups were individually housed and exposed to chronic unpredictable mild stress for 44 days simultaneously. The lactoferrin intervention group was provided with water containing 2% lactoferrin (2 g/100 ml). Behavioural tests were conducted at week 7. Upon completion of the behavioral tests, the rats were anesthetized with isoflurane, humanely euthanized using a rat guillotine, and tissue samples were collected for further experiments. The results indicated that lactoferrin intervention led to an increase in sucrose solution consumption, horizontal movement distance, number of cross platforms, and residence time in the target quadrant. Additionally, it resulted in an increase in jejunal tight junction protein ZO-1 expression and a suppression of serum expression of inflammatory factors, Lipopolysaccharide and Diamine oxidase. In summary, lactoferrin can regulate the metabolic disorder of intestinal flora, reduce intestinal permeability, and further regulate the metabolic balance of hippocampal tissues through the microbiota-gut-brain axis. This process ultimately alleviates the depression-like behavior in rats.

Advances in Novel Biomaterial-Based Strategies for Spinal Cord Injury Treatment.

Spinal cord injury (SCI) is a highly disabling neurological disorder. Its pathological process comprises an initial acute injury phase (primary injury) and a secondary injury phase (subsequent chronic injury). Although surgical, drug, and cell therapies have made some progress in treating SCI, there is no exact therapeutic strategy for treating SCI and promoting nerve regeneration due to the complexity of the pathological SCI process. The development of novel drug delivery systems to treat SCI is expected to significantly impact the individualized treatment of SCI due to its unique and excellent properties, such as active targeting and controlled release. In this review, we first describe the pathological progression of the SCI response, including primary and secondary injuries. Next, we provide a concise overview of newly developed nanoplatforms and their potential application in regulating and treating different pathological processes of SCI. Then, we introduce the existing potential problems and future clinical application perspectives of biomedical engineering-based therapies for SCI.

Dietary bile acids supplementation decreases hepatic fat deposition with the involvement of altered gut microbiota and liver bile acids profile in broiler chickens.

BACKGROUND: High-fat diets (HFD) are known to enhance feed conversion ratio in broiler chickens, yet they can also result in hepatic fat accumulation. Bile acids (BAs) and gut microbiota also play key roles in the formation of fatty liver. In this study, our objective was to elucidate the mechanisms through which BA supplementation reduces hepatic fat deposition in broiler chickens, with a focus on the involvement of gut microbiota and liver BA composition. RESULTS: Newly hatched broiler chickens were allocated to either a low-fat diet (LFD) or HFD, supplemented with or without BAs, and subsequently assessed their impacts on gut microbiota, hepatic lipid metabolism, and hepatic BA composition. Our findings showed that BA supplementation significantly reduced plasma and liver tissue triglyceride (TG) levels in 42-day-old broiler chickens (P < 0.05), concurrently with a significant decrease in the expression levels of fatty acid synthase (FAS) in liver tissue (P < 0.05). These results suggest that BA supplementation effectively diminishes hepatic fat deposition. Under the LFD, BAs supplementation increased the BA content and ratio of Non 12-OH BAs/12-OH BAs in the liver and increased the Akkermansia abundance in cecum. Under the HFD, BA supplementation decreased the BAs and increased the relative abundances of chenodeoxycholic acid (CDCA) and cholic acid (CA) in hepatic tissue, while the relative abundances of Bacteroides were dramatically reduced and the Bifidobacterium, Escherichia, and Lactobacillus were increased in cecum. Correlation analyses showed a significant positive correlation between the Akkermansia abundance and Non 12-OH BA content under the LFD, and presented a significant negative correlation between the Bacteroides abundance and CA or CDCA content under the HFD. CONCLUSIONS: The results indicate that supplementation of BAs in both LFD and HFD may ameliorate hepatic fat deposition in broiler chickens with the involvement of differentiated microbiota-bile acid profile pathways.

Effect of dapagliflozin on readmission and loop diuretics use in patients with acute heart failure: a retrospective propensity score-matched cohort study.

BACKGROUND: The efficacy of dapagliflozin in patients with acute heart failure remains unclear. OBJECTIVE: To investigate the impact of dapagliflozin (DAPA) on loop diuretics use and 90-day readmission in patients with acute heart failure. METHODS: In a retrospective cohort study, patients diagnosed with acute heart failure or chronic heart failure with acute exacerbation admitted to Fuyang People's Hospital from January 2021 to April 2023, this study used DAPA (at a dose of 10 mg once daily) in combination with standard treatment. The patients were divided into DAPA group and DAPA-Free group based on whether they used DAPA in acute heart failure. To minimize the influence of confounding factors and ensure comparability between groups, we used propensity score matching (PSM). RESULTS: A total of 399 patients were included, with 206 patients (51.63%) in the DAPA group and 193 patients (48.37%) in the DAPA-Free group. PSM produced 160 pairs. After PSM, there were no statistically significant differences between the DAPA and DAPA-Free groups in terms of readmission of all causes (16.88% vs. 18.12%, OR 0.9141, 95% CI 0.5385-1.552, log rank P = 0.739) or readmission for heart failure (11.88% vs. 15.0%, OR 0.9077, 95% CI 0.4441-1.469, log rank P = 0.484) after 90-day follow-up. Patients in the DAPA group had a lower mean daily dose of intravenous loop diuretics compared to the DAPA-Free group (20 mg/d vs. 30.00 mg/d, P<0.001), lower total loop diuretic dose during hospitalization (106.06 ± 31.23 mg vs. 144.50 ± 45.39 mg, P = 0.038) and a decreased number of diuretic types used (11.88% vs. 23.12%, P = 0.008). CONCLUSIONS: DAPA reduced the dose of intravenous loop diuretics. However, it did not improve all-cause readmission for 90 days or readmission for heart failure after discharge.

Risk of acute kidney injury in patients receiving vancomycin and concomitant piperacillin-tazobactam or carbapenem: a multicenter, retrospective cohort study.

BACKGROUND: Vancomycin (VAN) is empirically used with other broad-spectrum antibiotics, such as piperacillin-tazobactam (PTZ) or carbapenem (CBP). However, conflicting literature on the rates of acute kidney injury (AKI) of VAN with PTZ has been reported. RESEARCH DESIGN AND METHODS: A multicenter, retrospective cohort study of the risk of AKI was conducted in patients receiving VAN and concomitant PTZ or CBP from January 2019 and June 2023. RESULTS: In total, 514 eligible patients were included. AKI occurred in a total of 91 patients (17.70%). The prevalence of AKI was significantly higher in the VAN+PTZ group than in the VAN+CBP group (23.37% vs 15.27%, p = 0.028). The survival curves depicting the time to AKI showed the increased incidence and more rapid onset of AKI among patients in the VAN+PTZ group compared to those of the VAN+CBP group (HR 2.186, 95%CI 1.351-3.538, p = 0.0015). VAN+PTZ was associated with a consistently higher AKI rate over VAN+CBP (HR 1.762, 95%CI 1.111-2.795, p = 0.0161) throughout the 14-day combination therapy. VAN with concomitant PTZ, duration of combination therapy ≤ 4 days and VAN trough concentration > 20 mg/L were independent risk factors associated with AKI. CONCLUSION: The prevalence of AKI was found to be higher in patients receiving VAN+PTZ therapy compared to those receiving VAN+CBP therapy based on creatinine-defined AKI.

Thermal Annealing Effects on Long-lived Fluorenol Room Temperature Phosphorescence for Styrene Detection.

Fluorene derivatives have been widely developed in OLEDs because of its efficient fluorescence quantum efficiency, but for which unique rigid biphenyl planar structure and large conjugated system, we hypothesize that they have a great potential for room temperature phosphorescence (RTP) applications, and confirmed this conjecture by subjecting polyvinyl alcohol (PVA) and phosphors to thermal annealing. The cross-linked structure formed during thermal annealing judiciously modulates the phosphorescence emission characteristics of the fluorenol with the synergistic interaction between PVA and fluorenol. Specifically, the lifetime exhibited a substantial increase from 1352.2 ms to 2874.1 ms, accompanied by a quantum yield augmentation from 4.8% to 11.3%, which substantiate that cross-linked induced by thermal annealing effectively amplifies the phosphorescent intensity and stability of the phosphors, facilitating ultralong phosphorescent emission at ambient conditions. Furthermore, an effective probe based on this film is developed for its highly sensitive, quantitative and immediate detection of volatile organic compounds. This investigation not only proffers a novel paradigm for the development of advanced RTP materials but also imparts insightful considerations for optimizing the performance of polymers in conjunction with functional materials, encompassing bioimaging, sensing, and optoelectronic devices.

Multi-Omics Analysis by Machine Learning Identified Lysophosphatidic Acid as a Biomarker and Therapeutic Target for Porcine Reproductive and Respiratory Syndrome.

As a significant infectious disease in livestock, porcine reproductive and respiratory syndrome (PRRS) imposes substantial economic losses on the swine industry. Identification of diagnostic markers and therapeutic targets has been a focal challenge in PPRS prevention and control. By integrating metabolomic and lipidomic serum analyses of clinical pig cohorts through a machine learning approach with in vivo and in vitro infection models, lysophosphatidic acid (LPA) is discovered as a serum metabolic biomarker for PRRS virus (PRRSV) clinical diagnosis. PRRSV promoted LPA synthesis by upregulating the autotaxin expression, which causes innate immunosuppression by dampening the retinoic acid-inducible gene I (RIG-I) and type I interferon responses, leading to enhanced virus replication. Targeting LPA demonstrated protection against virus infection and associated disease outcomes in infected pigs, indicating that LPA is a novel antiviral target against PRRSV. This study lays a foundation for clinical prevention and control of PRRSV infections.

Measurable residual disease testing by next generation sequencing is more accurate compared with multiparameter flow cytometry in adults with B-cell acute lymphoblastic leukemia.

Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95 % Confidence Interval [CI], 1.34-8.5; P = 0.01) and worse survival (HR = 4.87 [1.53-15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTROPC-14005546]).

Effectiveness of low-level red light for controlling progression of Myopia in children and adolescents.

OBJECTIVE: To evaluate the effectiveness of low-level red light (LRL) in controlling the progression of myopia in children and adolescents. METHODS: A randomized controlled trial was conducted from March 2022 to June 2022 at the Xuzhou First People's Hospital. A total of 73 children and adolescents with myopia, between the ages of 6 and 14, and meeting the inclusion criteria, were randomly divided into two groups. The experimental group wore single vision spectacles with LRL intervention, while the control group wore single vision spectacles alone. Spherical equivalent refraction (SER), axial length (AL), subfoveal choroidal thickness (SFCT), and best-corrected visual acuity (BCVA) were measured for the participants. Data analysis was performed using chi-square test, independent samples t-test, and Mann-Whitney U test. To compare the changes in SER and AL between groups, we utilized the Generalized Estimating Equations (GEE) model. RESULTS: The experimental group was composed of 36 individuals, while the control group had 37. The mean age of the participants was 8.9 ± 2.0 years. No statistically significant distinctions in SER, AL and SFCT were observed between the two groups at baseline (P > 0.05). After 6 months of intervention, the experimental group's increase in SER (-0.01D; 95 % CI: -0.09, 0.06) was higher than that of the control group (-0.41D; 95 % CI: -0.51, -0.32), with a significance level of P < 0.001. Furthermore, the changes over time revealed significant differences between the two groups (Wald χ2group×time: 31.576, P < 0.001). The experimental group's AL increase (-0.02 mm; 95 % CI: -0.07, 0.03) was less than the control group's (0.22 mm; 95 % CI: 0.19, 0.25) (P < 0.001), with a significant difference over time between them (wald χ2group×time: 62.305, P < 0.001). SFCT change after 6 months in the experimental group was significantly greater (29.19 µm; 95 % CI: 18.48, 39.91) compared to that of the control group (-6.59 µm; 95 % CI: -14.28, 1.09) (P < 0.001). No adverse events were observed, and there was no evidence of fundus structural damage on OCT imaging. CONCLUSIONS: The findings suggest that low-level red light can effectively control myopia progression in children and adolescents within 6 months. No adverse reactions were observed.

Comparative effects of insulin pump and injection on gestational diabetes mellitus pregnancy outcomes and serum biomarkers.

BACKGROUND: Insulin injection is the basic daily drug treatment for diabetic patients. AIM: To evaluate the comparative impacts of continuous subcutaneous insulin infusion (CSII). METHODS: Based on the treatment modality received, the patients were allocated into two cohorts: The CSII group and the multiple daily injections (MDI) group, with each cohort comprising 210 patients. Comparative assessments were made regarding serum levels of serum-secreted frizzled-related protein 5, homocysteine, and C1q/TNF-related protein 9. Furthermore, outcomes such as fasting plasma glucose, 2-hour postprandial glucose levels, pain assessment scores, and the incidence of complications were evaluated post-treatment. RESULTS: The CSII group displayed notably lower fasting plasma glucose and 2-h postprandial glucose levels in comparison to the MDI group (P < 0.05). Subsequent analysis post-treatment unveiled a significantly higher percentage of patients reporting no pain in the CSII group (60.00%) in contrast to the MDI group (36.19%) (P < 0.05). Additionally, the CSII group exhibited a markedly reduced occurrence of fetal distress and premature rupture of membranes compared to the MDI group (P < 0.05). However, there were no significant variances observed in other pregnancy outcomes between the two groups (P > 0.05). A statistical analysis revealed a significant difference in the incidence of complications between the groups (χ 2 = 11.631, P = 0.001). CONCLUSION: The utilization of CSII via an insulin pump, as opposed to MDI, can significantly enhance the management of insulin administration in patients with GDM by diversifying the sites of insulin delivery. This approach not only promotes optimal glycemic control but also regulates metabolic factors linked to blood sugar, reducing the likelihood of adverse pregnancy outcomes and complications. The clinical relevance and importance of CSII in GDM management highlight its wide-ranging clinical usefulness.

Targeting sine oculis homeoprotein 1 (SIX1): A review of oncogenic roles and potential natural product therapeutics.

Sine oculis homeoprotein 1 (SIX1), a prominent representative of the homeodomain transcription factors within the SIX family, has attracted significant interest owing to its role in tumorigenesis, cancer progression, and prognostic assessments. Initially recognized for its pivotal role in embryonic development, SIX1 has emerged as a resurgent factor across a diverse set of mammalian cancers. Over the past two decades, numerous investigations have emphasized SIX1's dual significance as a developmental regulator and central player in oncogenic processes. A mounting body of evidence links SIX1 to the initiation of diverse cancers, encompassing enhanced cellular metabolism and advancement. This review provides an overview of the multifaceted roles of SIX1 in both normal development and oncogenic processes, emphasizing its importance as a possible therapeutic target and prognostic marker. Additionally, this review discusses the natural product agents that inhibit various pro-oncogenic mechanisms associated with SIX1.

Effects of low dietary calcium and lipopolysaccharide challenges on production performance, eggshell quality, and bone metabolism of laying hens.

Dietary calcium supply is essential for bone development and egg production in laying hens. This study investigated the effects of low dietary calcium and lipopolysaccharide (LPS) induced immune challenge in aged laying hens. A total of thirty-two Hy-Line Brown laying hens at 80 weeks old with an average laying rate of 62% were randomly divided into two groups and fed a normal calcium diet (3.57% Ca, NCA) or low calcium diet (2.08% Ca, LCA). At 88 weeks, the experiment was designed using a 2 × 2 factorial arrangement, and hens were intraperitoneally injected with saline (SAL) or LPS (0.5 mg/kg, 0.5 mg/kg, or 1.5 mg/kg body weight) once every 48 h intervals over 5 days. Production performance, egg quality, and bone physiology were evaluated. Results showed that LPS challenge decreased the hen-day egg production, egg mass, and eggshell traits (p < 0.05), but increased (p < 0.05) the calcium content of the tibia compared to SAL-injected hens. LCA diet decreased (p < 0.05) the hen-day egg production, and eggshell traits such as weight, percentage, strength, and thickness compared to the NCA diet. LCA diet increased the serum alkaline phosphatase (ALP) activity (p < 0.01) and tibial expression of ALP (p < 0.05) compared to NCA diet. LPS injection suppressed both the serum ALP activity (p < 0.05) and tibial expression of ALP (p < 0.001) compared to SAL injection. Furthermore, LPS injection increased (p < 0.05) the expression of both pro and anti-inflammatory cytokines in the spleen and tibia. The expression of cathepsin K ( Cts K ) and matrix metalloproteinase 9 ( MMP-9 ) were downregulated by LPS injection (p < 0.001). Broken and shell-less egg production and calcium content of eggshell, as well as tibial mRNA expression of osteocalcin ( Ocn ), tumor necrosis factor-alpha ( TNF-α ) and tartrate-resistant acid phosphatase ( TRAP ) were affected by the interaction (p < 0.05) of diet and injection. Therefore, this study demonstrated that to certain extents, low dietary calcium and LPS challenge dysregulated bone homeostasis and metabolism, with detrimental effects on the performance and eggshell quality of aged laying hens.

Analysis of the survival journey and post-traumatic growth process of children and their families following paediatric intensive care unit admission: A grounded theory study.

OBJECTIVES: Advances in critical care technology have lowered mortality rates among critically ill individuals. Nonetheless, survivors and their families may develop new physical, mental, cognitive, and social challenges due to paediatric intensive care unit (PICU) treatments, impacting their quality of life. The aim of this study was to investigate the survival journey and post-traumatic growth process of children and their families following PICU admission within the Chinese cultural context. METHODS: Twenty-six children who have been or are currently admitted to the PICU, alongside their parents and three PICU nurses, were chosen through purposive and theoretical sampling. Data collection involved face-to-face interviews and observations, with data analysis conducted through continuous comparison, open coding, and selective coding techniques. FINDINGS: A model outlining the survival journey and post-traumatic growth process of critically ill children and their families post PICU admission has been established. This model encompasses two central trajectories: an upward trajectory consisting of confusion, charging, action, and sublimation phases and a downward trajectory comprising confusion, doubt and fear, inhibition (including confrontation and avoidance), and drowning phases. CONCLUSIONS: Critically ill children and their families encounter diverse survival experiences and psychological journeys following traumatic events in the PICU. The survival experience has alternative upwards or downwards trajectories that are flexible/adaptable. Hence, offering timely psychological support can alter their developmental trajectories and foster post-traumatic growth.

Mitochondrial DNA-boosted dendritic cell-based nanovaccination triggers antitumor immunity in lung and pancreatic cancers.

Low migratory dendritic cell (DC) levels pose a challenge in cancer immune surveillance, yet their impact on tumor immune status and immunotherapy responses remains unclear. We present clinical evidence linking reduced migratory DC levels to immune-cold tumor status, resulting in poor patient outcomes. To address this, we develop an autologous DC-based nanovaccination strategy using patient-derived organoid or cancer cell lysate-pulsed cationic nanoparticles (cNPs) to load immunogenic DC-derived microvesicles (cNPcancer cell@MVDC). This approach transforms immune-cold tumors, increases migratory DCs, activates T cells and natural killer cells, reduces tumor growth, and enhances survival in orthotopic pancreatic and lung cancer models, surpassing conventional methods. In vivo imaging reveals superior cNPcancer cell@MVDC accumulation in tumors and lymph nodes, promoting immune cell infiltration. Mechanistically, cNPs enrich mitochondrial DNA, enhancing cGAS-STING-mediated DC activation and migration. Our strategy shifts cold tumors to a hot state, enhancing antitumor immunity for potential personalized cancer treatments.