Neutrophils impaired by anti-galectin-3 antibodies elicit inflammation of endothelial cells to aggregate the development of lupus cutaneous vasculitis.

OBJECTIVES: To investigate whether the interplay of anti-galectin-3 antibodies (anti-Gal3 Abs) with neutrophils contributes to the development of lupus cutaneous vasculitis. METHODS: Enzyme-linked immunosorbent assay was used to determine the serum level of anti-Gal3 Abs in lupus patients. Flow cytometry, quantitative PCR and western blot were performed to investigate the expression of cell surface receptors, proinflammatory cytokines and signalling molecules in neutrophils stimulated by serum from lupus patients or healthy controls (HCs) or anti-Gal3 Ab, respectively. Immunofluorescence was performed to visualise the formation of neutrophil extracellular traps (NETs). Human umbilical vein endothelial cells were co-cultured with the supernatants from neutrophils stimulated by anti-Gal3 Ab, and cytokine production was measured at mRNA and protein levels. Immunohistochemistry was adopted to reveal the distribution of Gal3, cytokines and myeloperoxidase within lupus skin lesions. REULTS: Serum levels of anti-Gal3 Abs were negatively correlated with peripheral counts of neutrophils. Anti-Gal3 Abs positive sera from SLE patients accelerated neutrophil death, altered cell phenotype and promoted formation of NETs with the involvement of p38 MAPK pathway. Supernatants collected from neutrophils co-cultured with anti-Gal3 Ab provoked endothelial cells to produce cytokines such as IL-1, ICAM-1, SELE and particularly IL-6. Consistently, IL-6 was higher in SLE patients with anti-Gal3 Ab positive sera and enriched in the area of vascular inflammation together with enhanced expression of Gal3 protein and infiltration of neutrophils. CONCLUSIONS: Overall, these findings suggested that neutrophils were crucial mediators in anti-Gal3 Ab induced lupus cutaneous vasculitis.

Exploring the mechanism of 6-Methoxydihydrosanguinarine in the treatment of lung adenocarcinoma based on network pharmacology, molecular docking and experimental investigation.

BACKGROUND: 6-Methoxydihydrosanguinarine (6-MDS) has shown promising potential in fighting against a variety of malignancies. Yet, its anti­lung adenocarcinoma (LUAD) effect and the underlying mechanism remain largely unexplored. This study sought to explore the targets and the probable mechanism of 6-MDS in LUAD through network pharmacology and experimental validation. METHODS: The proliferative activity of human LUAD cell line A549 was evaluated by Cell Counting Kit-8 (CCK8) assay. LUAD related targets, potential targets of 6-MDS were obtained from databases. Venn plot analysis were performed on 6-MDS target genes and LUAD related genes to obtain potential target genes for 6-MDS treatment of LUAD. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was utilized to perform a protein-protein interaction (PPI) analysis, which was then visualized by Cytoscape. The hub genes in the network were singled out by CytoHubba. Metascape was employed for GO and KEGG enrichment analyses. molecular docking was carried out using AutoDock Vina 4.2 software. Gene expression levels, overall survival of hub genes were validated by the GEPIA database. Protein expression levels, promotor methylation levels of hub genes were confirmed by the UALCAN database. Timer database was used for evaluating the association between the expression of hub genes and the abundance of infiltrating immune cells. Furthermore, correlation analysis of hub genes expression with immune subtypes of LUAD were performed by using the TISIDB database. Finally, the results of network pharmacology analysis were validated by qPCR. RESULTS: Experiments in vitro revealed that 6-MDS significantly reduced tumor growth. A total of 33 potential targets of 6-MDS in LUAD were obtained by crossing the LUAD related targets with 6-MDS targets. Utilizing CytoHubba, a network analysis tool, the top 10 genes with the highest centrality measures were pinpointed, including MMP9, CDK1, TYMS, CCNA2, ERBB2, CHEK1, KIF11, AURKB, PLK1 and TTK. Analysis of KEGG enrichment hinted that these 10 hub genes were located in the cell cycle signaling pathway, suggesting that 6-MDS may mainly inhibit the occurrence of LUAD by affecting the cell cycle. Molecular docking analysis revealed that the binding energies between 6-MDS and the hub proteins were all higher than - 6 kcal/Mol with the exception of AURKB, indicating that the 9 targets had strong binding ability with 6-MDS.These results were corroborated through assessments of mRNA expression levels, protein expression levels, overall survival analysis, promotor methylation level, immune subtypes andimmune infiltration. Furthermore, qPCR results indicated that 6-MDS can significantly decreased the mRNA levels of CDK1, CHEK1, KIF11, PLK1 and TTK. CONCLUSIONS: According to our findings, it appears that 6-MDS could possibly serve as a promising option for the treatment of LUAD. Further investigations in live animal models are necessary to confirm its potential in fighting cancer and to delve into the mechanisms at play.

RIPK3 deficiency blocks R-2-hydroxyglutarate-induced necroptosis in IDH-mutated AML cells.

Mutant isocitrate dehydrogenases (IDHs) produce R-2-hydroxyglutarate (R-2HG), which inhibits the growth of most acute myeloid leukemia (AML) cells. Here, we showed that necroptosis, a form of programmed cell death, contributed to the antileukemia activity of R-2HG. Mechanistically, R-2HG competitively inhibited the activity of lysine demethylase 2B (KDM2B), an α-ketoglutarate-dependent dioxygenase. KDM2B inhibition increased histone 3 lysine 4 trimethylation levels and promoted the expression of receptor-interacting protein kinase 1 (RIPK1), which consequently caused necroptosis in AML cells. The expression of RIPK3 was silenced because of DNA methylation in IDH-mutant (mIDH) AML cells, resulting in R-2HG resistance. Decitabine up-regulated RIPK3 expression and repaired endogenous R-2HG-induced necroptosis pathway in mIDH AML cells. Together, R-2HG induced RIPK1-dependent necroptosis via KDM2B inhibition in AML cells. The loss of RIPK3 protected mIDH AML cells from necroptosis. Restoring RIPK3 expression to exert R-2HG's intrinsic antileukemia effect will be a potential therapeutic strategy in patients with AML.

Thiotepa-busulfan-fludarabine-based conditioning as a promising approach prior to allogeneic hematopoietic stem cell transplantation in patients with blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive myeloid malignancy associated with a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) has emerged as a potential treatment strategy for BPDCN, standardized conditioning regimens remain lacking. In this manuscript, we present two cases of BPDCN that were treated with a thiotepa-busulfan-fludarabine (TBF)-based conditioning regimen prior to allo-HSCT. Both cases demonstrated complete remission post-transplantation, sustained donor chimerism, and remission maintenance, suggesting the potential efficacy of the TBF conditioning regimen for BPDCN transplantation. Given the small sample size in our study, we emphasize caution and advocate for larger studies to confirm the efficacy of TBF in the treatment of BPDCN.

Deep ultraviolet AlGaN-multiple quantum wells with photoluminescence enhanced by topological corner state.

The AlGaN-based deep ultraviolet light-emitting diode (DUV LED) has advantages of environmentally friendly materials, tunable emission wavelength, and easy miniaturization. However, an increase in Al composition leads to a decline in the lattice quality, thereby reducing the internal quantum efficiency (IQE). In addition, the light extraction efficiency (LEE) is limited due to the strong transverse magnetization polarization emission from the multiple quantum wells. Here, we designed the topological corner structure in AlGaN-MQWs, and the high electric field intensity in a tiny space at the corner results in an extremely high local density of optical states (LDOS), which could shorten the luminescence decay time of the emitter and increase the radiative rate by 26 times. Meanwhile, because the excited topological corner state resonance mode is a transverse-electric mode, enhancing only the transverse-electric luminescence without any gain for transverse-magnetic luminescence, thereby significantly improving the light extraction efficiency. Finally, according to theoretical calculations, the IQE could reach 68.75% at room temperature.

TBK1, a prioritized drug repurposing target for amyotrophic lateral sclerosis: evidence from druggable genome Mendelian randomization and pharmacological verification in vitro.

BACKGROUND: There is a lack of effective therapeutic strategies for amyotrophic lateral sclerosis (ALS); therefore, drug repurposing might provide a rapid approach to meet the urgent need for treatment. METHODS: To identify therapeutic targets associated with ALS, we conducted Mendelian randomization (MR) analysis and colocalization analysis using cis-eQTL of druggable gene and ALS GWAS data collections to determine annotated druggable gene targets that exhibited significant associations with ALS. By subsequent repurposing drug discovery coupled with inclusion criteria selection, we identified several drug candidates corresponding to their druggable gene targets that have been genetically validated. The pharmacological assays were then conducted to further assess the efficacy of genetics-supported repurposed drugs for potential ALS therapy in various cellular models. RESULTS: Through MR analysis, we identified potential ALS druggable genes in the blood, including TBK1 [OR 1.30, 95%CI (1.19, 1.42)], TNFSF12 [OR 1.36, 95%CI (1.19, 1.56)], GPX3 [OR 1.28, 95%CI (1.15, 1.43)], TNFSF13 [OR 0.45, 95%CI (0.32, 0.64)], and CD68 [OR 0.38, 95%CI (0.24, 0.58)]. Additionally, we identified potential ALS druggable genes in the brain, including RESP18 [OR 1.11, 95%CI (1.07, 1.16)], GPX3 [OR 0.57, 95%CI (0.48, 0.68)], GDF9 [OR 0.77, 95%CI (0.67, 0.88)], and PTPRN [OR 0.17, 95%CI (0.08, 0.34)]. Among them, TBK1, TNFSF12, RESP18, and GPX3 were confirmed in further colocalization analysis. We identified five drugs with repurposing opportunities targeting TBK1, TNFSF12, and GPX3, namely fostamatinib (R788), amlexanox (AMX), BIIB-023, RG-7212, and glutathione as potential repurposing drugs. R788 and AMX were prioritized due to their genetic supports, safety profiles, and cost-effectiveness evaluation. Further pharmacological analysis revealed that R788 and AMX mitigated neuroinflammation in ALS cell models characterized by overly active cGAS/STING signaling that was induced by MSA-2 or ALS-related toxic proteins (TDP-43 and SOD1), through the inhibition of TBK1 phosphorylation. CONCLUSIONS: Our MR analyses provided genetic evidence supporting TBK1, TNFSF12, RESP18, and GPX3 as druggable genes for ALS treatment. Among the drug candidates targeting the above genes with repurposing opportunities, FDA-approved drug-R788 and AMX served as effective TBK1 inhibitors. The subsequent pharmacological studies validated the potential of R788 and AMX for treating specific ALS subtypes through the inhibition of TBK1 phosphorylation.

Ectopic expression of the transcription factor ONECUT3 drives a complex karyotype in myelodysplastic syndromes.

Chromosomal instability is a prominent biological feature of myelodysplastic syndromes (MDS), with over 50% of patients with MDS harboring chromosomal abnormalities or a complex karyotype (CK). Despite this observation, the mechanisms underlying mitotic and chromosomal defects in MDS remain elusive. In this study, we identified ectopic expression of the transcription factor ONECUT3, which is associated with CKs and poorer survival outcomes in MDS. ONECUT3-overexpressing cell models exhibited enrichment of several notable pathways, including signatures of sister chromosome exchange separation and mitotic nuclear division with the upregulation of INCENP and CDCA8 genes. Notably, dysregulation of chromosome passenger complex (CPC) accumulation, besides the cell equator and midbody, during mitotic phases consequently caused cytokinesis failure and defective chromosome segregation. Mechanistically, the homeobox (HOX) domain of ONECUT3, serving as the DNA binding domain, occupied the unique genomic regions of INCENP and CDCA8 and transcriptionally activated these 2 genes. We identified a lead compound, C5484617, that functionally targeted the HOX domain of ONECUT3, inhibiting its transcriptional activity on downstream genes, and synergistically resensitized MDS cells to hypomethylating agents. This study revealed that ONECUT3 promoted chromosomal instability by transcriptional activation of INCENP and CDCA8, suggesting potential prognostic and therapeutic roles for targeting high-risk MDS patients with a CK.

Association of peripheral immune activation with amyotrophic lateral sclerosis and Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Recent studies have revealed the link between immune activation and neurodegenerative diseases. METHODS: By employing meta-analysis, we estimated the standardized mean difference (SMD) and their corresponding 95% confidence intervals (CIs) between the groups. RESULTS: According to the pre-set criteria, a total of 21 published articles including 2377 ALS patients and 1244 HCs, as well as 60 articles including 5111 PD patients and 4237 HCs, were identified. This study provided evidence of peripheral immune activation in the pathogenesis of ALS and PD. CONCLUSION: Our results suggested monitoring changes in peripheral blood immune cell populations, particularly lymphocyte subsets, will benefit understanding the developments and exploring reliable and specific biomarkers of these two diseases.

Effectiveness of perioperative low-dose esketamine infusion for postoperative pain management in pediatric urological surgery: a prospective clinical trial.

BACKGROUND: Postoperative pain is common in pediatric urological surgery. The study assess the impact of perioperative intravenous infusion of low-dose esketamine on postoperative pain in pediatric urological surgery. METHODS: Pediatric patients (n = 80) undergoing urological surgery were randomized into four groups. Patients in the control group were administered an analgesic pump containing only hydromorphone at a dose of 0.1 mg/kg (Hydromorphone Group 1, H1) or 0.15 mg/kg (Hydromorphone Group 2, H2). Patients in the experimental group were injected intravenously with 0.3 mg/kg of esketamine (Esketamine group 1, ES1) or equal volume of saline (Esketamine Group 2, ES2) during anesthesia induction. Esketamine 1.0 mg/kg and hydromorphone 0.1 mg/kg were added to the analgesic pump. Face, Leg, Activity, Crying, and Comfort (FLACC) scale or the Numerical Rating Scale (NRS) and adverse effects were recorded at 2, 6, 24, and 48 h postoperatively. Additionally, total and effective PCA button presses were recorded. RESULTS: In comparison to the H1 group, the pain scores were notably reduced at all postoperative time points in both the ES1 and H2 groups. The ES2 group exhibited lower pain scores only at 24 and 48 h postoperatively. When compared to the H2 group, there were no significant differences in pain scores at various postoperative time points in the ES2 group. However, the ES1 group demonstrated significantly lower pain scores at 6, 24 and 48 h postoperatively, and these scores were also significantly lower than those observed in the ES2 group. The total and effective number of PCA button presses in the ES1, ES2 and H2 group were lower than that in the H1 group (P < 0.001). The incidence of adverse effects within 48 h after surgery was 15% in ES1, 22% in ES2, 58% in H1, and 42% in H2, respectively (P = 0.021). CONCLUSIONS: The use of low-dose esketamine infusion in analgesia pump can effectively alleviates postoperative pain in pediatric urological patients, leading to a significant reduction in the number of analgesic pump button press. The combined approach of perioperative anesthesia induction and analgesia pump administration is recommended for optimal pain management in these patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry- ChiCTR2300073879 (24/07/2023).

Effective management of a rare case of primary renal intravascular large B-cell lymphoma with modified R-CHOP regimen: A case report.

Intravascular large B-cell lymphoma, known for its diverse organ involvement, presents significant diagnostic challenges, particularly when it affects the kidneys. This report highlights a rare case of primary renal intravascular large B-cell lymphoma in a 60-year-old male patient, who presented with persistent fever and renal dysfunction. The case underscores the intricacy of diagnosis and the efficacy of personalized treatment. Following the identification of primary renal intravascular large B-cell lymphoma, a modified R-CHOP regimen was administered, resulting in notable amelioration of symptoms and renal function following the initial treatment cycle. The patient achieved sustained complete remission without any complications after completing five subsequent R-CHOP cycles and two additional cycles of rituximab monotherapy, as confirmed by recent assessments. He is currently under regular follow-up for ongoing monitoring and improvement. This case adds to the limited yet expanding pool of knowledge concerning intravascular large B-cell lymphoma, emphasizing the necessity for personalized therapeutic strategies in atypical presentations. It also highlights the importance of early detection and customized intervention in managing rare lymphoma subtypes with unique organ involvement.

Effects of 90 dB pure tone exposure on auditory and cardio-cerebral system functions in macaque monkeys.

Excessive noise exposure presents significant health risks to humans, affecting not just the auditory system but also the cardiovascular and central nervous systems. This study focused on three male macaque monkeys as subjects. 90 dB sound pressure level (SPL) pure tone exposure (frequency: 500Hz, repetition rate: 40Hz, 1 min per day, continuously exposed for 5 days) was administered. Assessments were performed before exposure, during exposure, immediately after exposure, and at 7-, 14-, and 28-days post-exposure, employing auditory brainstem response (ABR) tests, electrocardiograms (ECG), and electroencephalograms (EEG). The study found that the average threshold for the Ⅴ wave in the right ear increased by around 30 dB SPL right after exposure (P < 0.01) compared to pre-exposure. This elevation returned to normal within 7 days. The ECG results indicated that one of the macaque monkeys exhibited an RS-type QRS wave, and inverted T waves from immediately after exposure to 14 days, which normalized at 28 days. The other two monkeys showed no significant changes in their ECG parameters. Changes in EEG parameters demonstrated that main brain regions exhibited significant activation at 40Hz during noise exposure. After noise exposure, the power spectral density (PSD) in main brain regions, particularly those represented by the temporal lobe, exhibited a decreasing trend across all frequency bands, with no clear recovery over time. In summary, exposure to 90 dB SPL noise results in impaired auditory systems, aberrant brain functionality, and abnormal electrocardiographic indicators, albeit with individual variations. It has implications for establishing noise protection standards, although the precise mechanisms require further exploration by integrating pathological and behavioral indicators.

Clinical human activity recognition based on a wearable patch of combined tri-axial ACC and ECG sensors.

Background: In digital medicine, human activity recognition (HAR) can be used to track and assess a patient's progress throughout rehabilitation, enhancing the quality of life for the elderly and the disabled. Methods: A patch-type flexible sensor that integrated dynamic electrocardiogram (ECG) and acceleration signal (ACC) was used to record the signals of the various behavioral activities of 20 healthy volunteers and 25 patients with pneumoconiosis. Seven HAR tasks were then carried out on the data using four different deep learning methods (CNN, LSTM, CNN-LSTM and GRU). Results: When ECG and ACC were obtained simultaneously, the overall accuracy rates of HAR for healthy group were 0.9371, 0.8829, 0.9843 and 0.9486 by the CNN, LSTM, CNN-LSTM and GRU models, respectively. In contrast, the overall accuracy rates of HAR for the pneumoconiosis patients' group were 0.8850, 0.7975, 0.9425 and 0.8525 by the four corresponding models. The accuracy of HAR for both groups using all four models is higher than when only ACC signal is detected. Conclusion: The addition of the ECG signal significantly improves HAR outcomes in the group of healthy individuals, while having relatively less enhancing effects on the group of patients with pneumoconiosis. When ECG and ACC signals were combined, the increase in HAR accuracy was notable compared to cases where no ECG data was provided. These results suggest that the combination of ACC and ECG data can represent a novel method for the clinical application of HAR.

The estimated effect of increasing fruit interventions on controlling body weight in children and adolescents: A meta-analysis.

BACKGROUND: The impact of increased fruit consumption on weight change remains a matter of debate. OBJECTIVE: This study aimed to evaluate the effects of interventions targeted at promoting fruit consumption and managing body weight in children and adolescents. METHODS: Four electronic databases, including PubMed, Web of science, Embase, and the Cochrane Library, were searched from January 1, 2000, to October 10th, 2023, to identify Randomized controlled trials (RCTs) that assessed changes in fruit consumption and obesity indicators. RESULTS: A total of 22 trials including 12,678 participants who met our inclusion criteria were selected for this review. The meta-analysis demonstrated that the interventions increased fruit intake (MD = 78.58 g/day (95% CI 53.09 to 104.07), P < 0.001) in children and adolescents. The mean reduction of body mass index was 0.27 kg/m2 (95% CI -0.59 to 0.05 kg/m2, P = 0.101). And no significant decreases were observed in body mass index-z scores, but there was a significant decrease in waist circumference (MD = -0.65 cm (95% CI -1.15 to -0.05 cm), P < 0.05). Increased fruit intake was shown to be associated with a lower prevalence of obesity when compared to the control group (odds ratio [OR]: 0.74, 95% CI 0.60 to 0.90), P < 0.05). CONCLUSIONS: This meta-analysis provided evidence that interventions aimed at increasing fruit consumption were effective at reducing obesity prevalence.

The impact of dietary and sleep rhythms on blood pressure in children and adolescents: a cross-sectional study.

Evidence about the relationship between meal and sleep time and CVD in children is scarce. The aims of this study were to describe the association between life rhythm patterns and blood pressure in children. This research was conducted among 5,608 children aged 6 to 15 years old in Chongqing and Sichuan provinces in 2021 and 2022. Dietary and sleep rhythms information was collected. The time of the first meal and last meal, and sleep time, were obtained. The mean age was 10.48 ± 2.24 years old, with 2958 (52.75%) male participants. The mean feeding window on weekdays was 11.69 h, 12.42 h, and 13.23 h for participants aged 6-7 years old, 8-12 years old and 13-15 years old, respectively. Weekday feeding window and last mealtime were positively correlated with blood pressure levels. And the changes in the feeding window between weekdays and weekends were significantly correlated with BP. Sleep duration and change in wake time were significantly correlated with SBP. Based on these results, this study identified the optimal combination of dietary and sleep rhythm interventions for children younger than 12 years of age and aged 12 and older, respectively. Disorder dietary and sleep rhythms disorders may correlate with elevated blood pressure levels, suggesting developing optimal dietary and sleep rhythm patterns could prevent the incidence of CVDs in children. The optimal dietary rhythm was defined by the indexes of breakfast time, dinner time and daily feeding window. As good meal patterns are defined as satisfied the following three items: for children younger than 12 years should have breakfast after 7:30 am; aged 12 years and over should have breakfast after 7 am; having dinner before 6 pm; daily feeding window less than 12.5 h. And less optimal dietary rhythm should satisfy any condition or eat dinner between 6 pm and 8 pm; and poor dietary rhythm should not satisfy any of the three criteria and eat dinner after 8 pm. Children with optimal dietary rhythm (in group A) had lower SBP (P < 0.001), DBP (P = 0.002) and MAP (P < 0.001) than those in group C.

DUSP1 Signaling Pathway Regulates Cytarabine Sensitivity in Acute Myeloid Leukemia.

Objectives: Dual specificity phosphatase 1 (DUSP1) is high-expressed in various cancers and plays an important role in the cellular response to agents that damage DNA. We aimed to investigate the expressions and mechanisms of DUSP1 signaling pathway regulating cytarabine (Ara-C) resistance in acute myeloid leukemia (AML). Methods: Immunohistochemistry was performed on bone marrow biopsy specimens from AML and controls to explore the expression of DUSP1. Western blot and Q-PCR were used to detect the protein and mRNA expression levels. MTT assay was used to detect the proliferation of cells. Cell apoptosis was detected by flow cytometry. The immune protein-protein interaction (PPI) network of DUSP1 was analyzed in the platform of Pathway Commons, and immune infiltration analysis was used to study the immune microenvironment of AML. Results: We found that the expression levels of DUSP1 in AML patients exceeded that in controls. Survival analysis in public datasets showed that AML patients with higher levels of DUSP1 had poor clinical outcomes. Further public data analysis indicated that DUSP1 was overexpressed in NRAS mutated AML. DUSP1 knockdown by siRNA could sensitize AML cells to Ara-C treatments. The phosphorylation level of mitogen-activated protein kinase (MAPK) pathway was significantly elevated in DUSP1 down-regulated NRAS G13D mutated AML cells. The PPI analysis showed DUSP1 correlated with immune gene CREB1 and CXCL8 in NRAS mutated AML. We also revealed a correlation between tumor-infiltrating immune cells in RAS mutated AML microenvironment. Conclusion: Our findings suggest that DUSP1 signaling pathways may regulate Ara-C sensitivity in AML.

Single-cell transcriptome and metagenome profiling reveals the genetic basis of rumen functions and convergent developmental patterns in ruminants.

The rumen undergoes developmental changes during maturation. To characterize this understudied dynamic process, we profiled single-cell transcriptomes of about 308,000 cells from the rumen tissues of sheep and goats at 17 time points. We built comprehensive transcriptome and metagenome atlases from early embryonic to rumination stages, and recapitulated histomorphometric and transcriptional features of the rumen, revealing key transitional signatures associated with the development of ruminal cells, microbiota, and core transcriptional regulatory networks. In addition, we identified and validated potential cross-talk between host cells and microbiomes and revealed their roles in modulating the spatiotemporal expression of key genes in ruminal cells. Cross-species analyses revealed convergent developmental patterns of cellular heterogeneity, gene expression, and cell-cell and microbiome-cell interactions. Finally, we uncovered how the interactions can act upon the symbiotic rumen system to modify the processes of fermentation, fiber digestion, and immune defense. These results significantly enhance understanding of the genetic basis of the unique roles of rumen.

The optimal time restricted eating interventions for blood pressure, weight, fat mass, glucose, and lipids: A meta-analyses and systematic review.

BACKGROUND: No previous systematic review or meta-analysis has evaluated the effect of optimal time-restricted eating (TRE) interventions on cardiovascular (CVD) risk factors. This meta-analysis aimed to illustrate the effect of a suitable TRE on CVD risk factors. METHODS: A systematic review was performed to identify trials reporting the effects of TRE, relative to non-diet controls, on CVD risk factors in humans. A random-effects model was used to evaluate the effect sizes, and the results are expressed as the mean difference (MD) and 95% confidence intervals (CIs). Subgroup analyses were performed to examine the influence of the study population, age, duration of intervention, and baseline mean BMI on the CVD indexes. RESULTS: TRE intervention significantly reduced systolic pressure (SBP) (MD: -3.45 mmHg; 95%CI:(-6.20,-0.71) mmHg; P = 0.01), body weight (MD: -1.63 Kg; 95%CI:(-2.09,-1.17) Kg; P<0.001), body mass index (BMI) (MD: -0.47 Kg/m2; 95% CI: (-0.72, -0.22) Kg/m2; P<0.001), and fat mass (MD: -0.98 Kg; 95% CI: (-1.51,-0.44) Kg; P<0.001), and reduced blood glucose levels. Based on the results of subgroup analysis, this meta-analysis identified the optimal TRE for BP (with a 6 h feeding window, last eating time point at 6-8 PM, and male participants with obesity and aged ≥ 45 years), obesity (with a 6 h feeding window, last eating time point at 6-8 PM, and female participants aged ≥ 45 years), lipids (with an 8 h feeding window, last eating time point at 6-8 PM, and male participants aged < 45 years), and glucose (with a 10-12 h feeding window, last eating time point before 6 PM, and female participants aged < 45years). CONCLUSIONS: Relative to a non-diet control, TRE is effective for the improvement of CVD risks. Moreover, individual TRE interventions should be developed for different populations to achieve the most effective health improvement for CVD risk factors.

Nuts consumption and hypertension risks in children: a mediating role of circulating lipid metabolites.

BACKGROUND: Although nuts play an important role in preventing cardiovascular disease, the metabolic cues by which nuts regulate blood pressure have not been fully understood.Aims:We conducted a nested case-control study in a prospective cohort study of Southwest China children to explore the potential lipid metabolites related to the relationship between nut dietary and blood pressure. METHODS: Forty-three hypertension cases and 53 controls serum samples were obtained for lipidomic data analysis using a liquid chromatography mass spectrometry platform. RESULTS: We identified four lipid metabolites that are associated with nut intake by a generalized linear model and logistic regression analysis, including phosphatidylglycerol 43:6 [PG (43:6)], phosphatidylcholine 18:0/20:3 [PC (18:0/20:3)], and two phosphatidylethanolamine (PE) compounds [PE (P-16:0/20:4) and PE (P-22:0/18:2)]. Logistic regression analysis indicated that the levels of PG (43:6) and PE (P-16:0/20:4) were negatively associated with hypertension in children, which might be useful biomarkers for predicting childhood hypertension. Further mediation analysis revealed that PG (43:6) and PC (18:0/20:3) function as mediating variables between nut intake and blood pressure levels. CONCLUSION: This study provides scientific evidence that nut consumption induces some beneficial changes in lipid metabolism, which may reduce the risk of hypertension in children.