Multi-Omics Profiles of Small Intestine Organoids in Reaction to Breast Milk and Different Infant Formula Preparations.

Ensuring optimal infant nutrition is crucial for the health and development of children. Many infants aged 0-6 months are fed with infant formula rather than breast milk. Research on cancer cell lines and animal models is limited to examining the nutrition effects of formula and breast milk, as it does not comprehensively consider absorption, metabolism, and the health and social determinants of the infant and its physiology. Our study utilized small intestine organoids induced from human embryo stem cell (ESC) to compare the nutritional effects of breast milk from five donors during their postpartum lactation period of 1-6 months and three types of Stage 1 infant formulae from regular retail stores. Using transcriptomics and untargeted metabolomics approaches, we focused on the differences such as cell growth and development, cell junctions, and extracellular matrix. We also analyzed the roles of pathways including AMPK, Hippo, and Wnt, and identified key genes such as ALPI, SMAD3, TJP1, and WWTR1 for small intestine development. Through observational and in-vitro analysis, our study demonstrates ESC-derived organoids might be a promising model for exploring nutritional effects and underlying mechanisms.

Transcriptome and metabolome analyses reveal the effects of formula and breast milk on the growth and development of human small intestinal organoids.

Breast milk is widely acknowledged as the ideal nutritional resource for infants and can well meet the nutritional requirements for baby's growth and development. Infant formula is a substitute for breast milk, designed to closely mimic its composition and function for breast milk. Most of the previous studies used tumor colorectal cancer cell lines to study the nutritional potency of formula and its components, so realistic data closer to the baby could not be obtained. Small intestinal organoids, derived from differentiated human embryonic stem cells, can be used to simulate nutrient absorption and metabolism in vitro. In this experiment, we used small intestinal organoids to compare the nutrient absorption and metabolism of three infant formulae for 0-6 months with breast milk samples. Transcriptome and metabolome sequencing methods were used to analyze the differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs). The pathways related to DEGs, DEMs were enriched using GO, KEGG, GSEA and other methods to investigate their biological characteristics. We have found that both formula and breast milk promote the development of the infant's immune system, nutrient absorption and intestinal development. In PMH1 we found that the addition of oligofructose to milk powder promoted lipid metabolism and absorption. In PMH2 we found that whey protein powder favours the development of the immune system in infants. In PMH3 we found that oligogalactans may act on the brain-gut axis by regulating the intestinal flora, thereby promoting axon formation and neural development. By linking these biological properties of the milk powder with its composition, we confirmed the effects of added ingredients on the growth and development of infants. Also, we demonstrated the validity of small intestine organoids as a model for absorption and digestion in vitro. Through the above analyses, the advantages and disadvantages of the roles of formula and breast milk in the growth and metabolism of infants were also compared.

Acute-phase plasma proteomics of rabbit lung VX2 tumors treated by image-guided microwave ablation.

Purpose: To explore the plasma proteomic changes of rabbit lung VX2 tumors treated by microwave ablation, and to explore the molecular pathway mechanisms that may be involved. Methods: New Zealand white rabbits were inoculated with VX2 tumor cell suspension in the right lower lung and treated with microwave ablation after 2-3 weeks of tumor formation. Blood was collected at 5 time points (TP1~TP5) before and after ablation by cardiac blood sampling and pre-treated before proteomic analysis. The plasma proteome was analyzed by Data-Independent Acquisition (DIA). Results: Different molecular pathways were activated at different time points:(i) TP1vsTP2: more proteins were down-regulated and enrichment analysis showed that the proteasome pathway was activated. The abnormal protein folding process involved in this pathway is closely related to the process of tumor development. (ii) TP2vsTP3: more proteins were up-regulated although the number of differentially differentiated proteins was lower and enrichment analysis showed that the phagosome pathway was activated. After microwave ablation inactivates tumor cells, it activates the phagosomal pathway for immune clearance of necrotic tumor tissue. (iii) TP3vsTP4: more down-regulated proteins, enrichment analysis showed that cysteine and methionine metabolism pathway was activated. Decreased metabolism of these amino acids suggests that cancer progression may be blocked after microwave ablation therapy. (iv) TP4vsTP5: the number of differential proteins was less and more down-regulated proteins, enrichment analysis showed that glutathione metabolism and metabolism of xenobiotics by cytochrome P450 pathway were activated. The down-regulated proteins in this pathway may suggest that microwave ablation may have reduced resistance to certain chemotherapeutic agents following. Conclusions: In the process of lung cancer treatment by microwave ablation, the changes of proteins on the possible molecular pathways at each time point are related to lung cancer, and not only involve some simple inflammatory reactions, and some of the proteins released by destroying the tumor cells can be used as possible drug binding sites and reduce drug resistance.

Tudor-SN exacerbates pathological vascular remodeling by promoting the polyubiquitination of PTEN via NEDD4-1.

BACKGROUND: Dysregulation of vascular homeostasis can induce cardiovascular diseases and increase global mortality rates. Although lineage tracing studies have confirmed the pivotal role of modulated vascular smooth muscle cells (VSMCs) in the progression of pathological vascular remodeling, the underlying mechanisms are still unclear. METHODS: The expression of Tudor-SN was determined in VSMCs of artery stenosis, PDGF-BB-treated VSMCs and atherosclerotic plaque. Loss- and gain-of-function approaches were used to explore the role of Tudor-SN in the modulation of VSMCs phenotype both in vivo and in vitro. RESULTS: In this study, we demonstrate that Tudor-SN expression is significantly elevated in injury-induced arteries, atherosclerotic plaques, and PDGF-BB-stimulated VSMCs. Tudor-SN deficiency attenuates, but overexpression aggravates the synthetic phenotypic switching of VSMCs and pathological vascular remodeling. Loss of Tudor-SN also reduces atherosclerotic plaque formation and increases plaque stability. Mechanistically, PTEN, the major regulator of the MAPK and PI3K-AKT signaling pathways, plays a vital role in Tudor-SN-mediated regulation on proliferation and migration of VSMCs. Tudor-SN facilitates the polyubiquitination and degradation of PTEN via NEDD4-1, thus exacerbating vascular remodeling under pathological conditions. BpV (HOpic), a specific inhibitor of PTEN, not only counteracts the protective effect of Tudor-SN deficiency on proliferation and migration of VSMCs, but also abrogates the negative effect of carotid artery injury-induced vascular remodeling in mice. CONCLUSIONS: Our findings reveal that Tudor-SN deficiency significantly ameliorated pathological vascular remodeling by reducing NEDD4-1-dependent PTEN polyubiquitination, suggesting that Tudor-SN may be a novel target for preventing vascular diseases.

Preservation of cfRNA in cytological supernatants for cfDNA & cfRNA double detection in non-small cell lung cancer patients.

BACKGROUD: Supernatants from various cytological samples, including body cavity effusion, sputum, bronchoalveolar lavage fluid (BALF), and needle aspiration, have been validated for detecting genetic alterations using cell-free DNA (cfDNA) in patients with non-small cell lung cancer (NSCLC). However, the sensitivity of fusion variations detection remains challenging. The protection of cell-free RNA (cfRNA) is critical for resolving the issue. METHODS: A protective solution (PS) was applied for preserving cfRNA in cytological supernatant (CS), and the quality of protected cfRNA was assessed by cycle threshold (CT) values from reverse transcription quantitative polymerase chain reaction (RT-qPCR). Furthermore, we collected an additional set of malignant cytological and matched tumor samples from 84 NSCLC patients, cfDNA & cfRNA extraction and double detection for driver gene mutations was validated using the multi-gene mutations detection by RT-qPCR. RESULTS: Under the optimal protection system, 91.0% (101/111) of cfRNA were protected effectively. Among the 84 NSCLC patient samples, seven cytological samples failed the tests. In comparison with tumor samples, the overall sensitivity and specificity of detecting driver genes of supernatant cfDNA and cfRNA were 93.8% (74/77) and 100% (77/77), respectively. Notably, when focusing exclusively on patients with fusion gene changes, both sensitivity and specificity reached 100% (11/11) for EML4-ALK, ROS1, RET fusions, and MET ex14 skipping. CONCLUSION: These findings suggest that cfDNA & cfRNA extraction and double detection strategy recommended in this study improve the accuracy of driver genes mutations test, especially for RNA-based assay.

Clinical and immunoserological characteristics of anti-p200 pemphigoid: Comparisons of patients with epitope spreading and non-epitope spreading.

BACKGROUND: Anti-p200 pemphigoid is a rare autoimmune subepidermal blistering disease. Although the phenomenon of epitope spreading has been reported to be common in anti-p200 pemphigoid, the association between its clinical and immunoserological features has yet to be elucidated. OBJECTIVES: Our aim was to compare the clinical and immunoserological characteristics of anti-p200 pemphigoid patients with and without epitope spreading. METHODS: We performed a retrospective cohort study encompassing 30 patients with anti-p200 pemphigoid between January 2015 and December 2022. The clinical and immunoserological characteristics of anti-p200 pemphigoid were analyzed using combined immunoserological assays. RESULTS: Epitope spreading was observed in 11 of 30 patients (36.7%) with anti-p200 pemphigoid. Compared with patients in the non-epitope spreading group, patients in the epitope spreading group showed more heterogeneous clinical presentations (P = 0.018), a higher proportion of mucosal involvement (P = 0.003), higher Bullous Pemphigoid Disease Area Index (BPDAI) scores for skin erosions/blisters (P = 0.018), mucosal erosions/blisters (P = 0.001), activity (P = 0.017) and total scores (P = 0.022), and required a higher initial dose of prednisone for disease control (P = 0.040). CONCLUSIONS: This study supported the idea that anti-p200 pemphigoid was prone to epitope spreading. Anti-p200 pemphigoid patients with epitope spreading are more likely to present heterogeneous clinical phenotypes, frequent mucosal involvement, and a more severe and recalcitrant disease course.

Alkalinity control in sludge propels the conversion of concrete slurry waste into micro- and nano-sized biogenic CaCO3.

The utilization of Bacillus sp. for the production of bio-CaCO3 in concrete crack repair and strength enhancement has attracted considerable attention. However, microbial-induced calcium carbonate precipitation (MICP) has yet to be explored as a precedent with activated sludge. Here calcium sourced from concrete slurry waste (CSW) and carbon from sludge microbial ß-oxidation under alkaline were used to generate micro/nano CaCO3. The results indicate that the main crystalline form of the generated precipitated particles is calcite, with a particle size ranging from 0.7 to 10 µm. Minimal heavy metals were found in the supernatant following settling. And at the optimum pH of 8.5-9, carbon capture reached 743 mg L-1, and CaCO3 production reached 1,191 mg L-1, and dominant phylum were Proteobacteria and Bacteroidota, with Thauera being a prevalent genus adept in ß-oxidation. Mass balance analysis showed that alkali promotes microbial ß-oxidation of organisms to produce CO2 and facilitate storage. Thus, the alkaline regulation of metabolism between microbe and CSW provides a novel way of sludge to initiate MICP.

Individual and combined effects of famine exposure and obesity parameters on type 2 diabetes in middle-aged and older adults: A population-based cross-sectional study.

Malnutrition early in life may have adverse effects on health later in life. The relationship between malnutrition and obesity parameters (body mass index [BMI] and waist circumference [WC]) and type 2 diabetes is inconsistent. This study aimed to identify the effects of famine exposure and obesity parameters on type 2 diabetes individually or in combination among middle-aged and older adults in China. Data were extracted from the China Health and Retirement Longitudinal Study Wave1 in 2011. The sample involved 13,065 adults aged 45 to 90. The t- or F test was employed to compare age among groups. The chi-square test was utilized to compare baseline characteristics according to the categorical WC levels/BMI levels/famine exposure and examine between-group differences in type 2 diabetes (diabetes and non-diabetes). Odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression models to estimate the individual and combined associations of BMI/WC levels and famine exposure with the prevalence of type 2 diabetes. In this study, 1559 (11.93%) individuals were exposed to Chinese famine during their fetal stage, 5132 (39.28%) and 4428 (33.89%) in childhood and adolescence/adulthood, respectively. Among BMI measurements, 3780 (28.93%) were overweight, and 1487 (11.38%) were obese, whereas WC measurements showed that 5408 (41.39%) were obesity. In addition, 831 (45.48%) males and 996 (54.52%) females reported type 2 diabetes. In multivariable-adjusted regression models, obesity parameters and famine exposure were independently associated with type 2 diabetes prevalence among all participants (P < .001). In the interaction analysis, there existed a trend of higher odds for prevalence of type 2 diabetes across all groups compared to the combination of no-exposed and normal BMI/WC level group (the most increase in odds, adolescence/adulthood-exposed group with central obesity in WC levels: OR 4.51 (95% CI = 3.42-5.95); adolescence/adulthood-exposed group with obesity in BMI levels: OR 5.84 (95% CI = 4.11-8.30; P for interaction <.001). The findings for females exhibited similar to the overall participants, when by gender stratification. Our results suggest famine exposure and obesity parameters have positive combined effects on type 2 diabetes in middle-aged and older adults in China.

Exploration of small molecule compounds targeting abdominal aortic aneurysm based on CMap database and molecular dynamics simulation.

OBJECTIVE: The mitigation of abdominal aortic aneurysm (AAA) growth through pharmaceutical intervention offers the potential to avert the perils associated with AAA rupture and the subsequent need for surgical intervention. Nevertheless, the existing effective drugs for AAA treatment are limited, necessitating a pressing exploration for novel therapeutic medications. METHODS: AAA-related transcriptome data were downloaded from GEO, and differentially expressed genes (DEGs) in AAA tissue were screened for GO and KEGG enrichment analyses. Small molecule compounds and their target proteins with negative connectivity to the AAA expression profile were predicted in the Connectivity Map (CMap) database. Molecular docking and molecular dynamics simulation were performed to predict the binding of the target protein to the small molecule compound, and the MM/GBSA method was used to calculate the binding free energy. Cluster analysis was performed using the cluster tool in the GROMACS package. An AAA cell-free model was built, and CETSA experiments were used to demonstrate the binding ability of small molecules to the target protein in cells. RESULTS: A total of 2244 DEGs in AAA were obtained through differential analysis, and the DEGs were mainly enriched in the tubulin binding biological function and cell cycle pathway. The CMap results showed that Apicidin had a potential therapeutic effect on AAA with a connectivity score of -97.74, and HDAC4 was the target protein of Apicidin. Based on literature, HDAC4-Apicidin was selected as the subsequent research object. The lowest affinity of Apicidin-HDAC4 molecular docking was -8.218 kcal/mol. Molecular dynamics simulation results indicated that Apicidin-HDAC4 could form a stable complex. MM/GBSA analysis showed a total binding free energy of -55.40 ± 0.79 kcal/mol, and cluster analysis showed that there were two main conformational clusters during the binding process, accounting for 22.4% and 57.8%, respectively. Apicidin could form hydrogen bonds with surrounding residues for stable binding. CETSA experiment proved the stable binding ability of Apicidin and HDAC4. CONCLUSION: Apicidin inhibited HDAC4 in AAA and exhibited favorable protein-ligand interactions and stability, making it a potential candidate drug for treating AAA.

Using integrated transcriptomics and metabolomics to explore the effects of infant formula on the growth and development of small intestinal organoids.

Infant formulas are designed to provide sufficient energy and the necessary nutrients to support the growth and development of newborns. Currently, research on the functions of formula milk powder focuses on clinical research and cell experiments, and there were many cell experiments that investigated the effect of infant formulas on cellular growth. However, most of the cells used are tumor cell lines, which are unable to simulate the real digestion process of an infant. In this study, we innovatively proposed a method that integrates human small intestinal organoids (SIOs) with transcriptomics and metabolomics analysis. We induced directed differentiation of human embryonic stem cells into SIOs and simulated the intestinal environment of newborns with them. Then, three kinds of 1-stage infant formulas from the same brand were introduced to simulate the digestion, absorption, and metabolism of the infant intestine. The nutritional value of each formula milk powder was examined by multi-omics sequencing methods, including transcriptomics and metabolomics analysis. Results showed that there were significant alterations in gene expression and metabolites in the three groups of SIOs after absorbing different infant formulas. By analyzing transcriptome and metabolome data, combined with GO, KEGG, and GSEA analysis, we demonstrated the ability of SIOs to model the different aspects of the developing process of the intestine and discovered the correlation between formula components and their effects, including Lactobacillus lactis and lactoferrin. The study reveals the effect and mechanisms of formula milk powder on the growth and development of infant intestines and the formation of immune function. Furthermore, our method can help to construct a multi-level assessment model, detect the effects of nutrients, and evaluate the interactions between nutrients, which is helpful for future research and development of infant powders.

Cell-type-specific expression analysis of liver transcriptomics with clinical parameters to decipher the cause of intrahepatic inflammation in chronic hepatitis B.

Functional cure for chronic hepatitis B (CHB) remains challenging due to the lack of direct intervention methods for hepatic inflammation. Multi-omics research offers a promising approach to understand hepatic inflammation mechanisms in CHB. A Bayesian linear model linked gene expression with clinical parameters, and population-specific expression analysis (PSEA) refined bulk gene expression into specific cell types across different clinical phases. These models were integrated into our analysis of key factors like inflammatory cells, immune activation, T cell exhaustion, chemokines, receptors, and interferon-stimulated genes (ISGs). Validation through multi-immune staining in liver specimens from CHB patients bolstered our findings. In CHB patients, increased gene expression related to immune cell activation and migration was noted. Marker genes of macrophages, T cells, immune-negative regulators, chemokines, and ISGs showed a positive correlation with serum alanine aminotransferase (ALT) levels but not hepatitis B virus DNA levels. The PSEA model confirmed T cells as the source of exhausted regulators, while macrophages primarily contributed to chemokine expression. Upregulated ISGs (ISG20, IFI16, TAP2, GBP1, PSMB9) in the hepatitis phase were associated with T cell and macrophage infiltration and positively correlated with ALT levels. Conversely, another set of ISGs (IFI44, ISG15, IFI44L, IFI6, MX1) mainly expressed by hepatocytes and B cells showed no correlation with ALT levels. Our study presents a multi-omics analysis integrating bulk transcriptomic, single-cell sequencing data, and clinical data from CHB patients to decipher the cause of intrahepatic inflammation in CHB. The findings confirm that macrophages secrete chemokines like CCL20, recruiting exhausted T cells into liver tissue; concurrently, hepatocyte innate immunity is suppressed, hindering the antiviral effects of ISGs.

Spatial position changes in the semicircular canals may be the anatomical basis of Meniere's disease: a preliminary study based on ultra-high-resolution computed tomography (CT) and intelligent segmentation.

Background: Meniere's disease (MD) is an ear-related vestibular disorder accompanied by vertigo, hearing loss, and tinnitus. The anatomical structure and spatial position of the semicircular canals are important for understanding vestibular function and disease; however, research on MD and the effect of anatomical changes in the semicircular canals is limited. This study explored the relationship between the spatial location of the semicircular canals and MD using ultra-high-resolution computed tomography (U-HRCT) and intelligent segmentation. Methods: Isotropic U-HRCT images obtained from patients with MD and healthy controls (HCs) were retrospectively analyzed. We extracted the semicircular canal structures and extracted their skeleton. The plane of the skeleton of each semicircular canal was fitted separately. The mutual angles between the semicircular canals, and the angles between each semicircular canal and each plane of the coordinate system were measured. Results: Among 45 MD-affected ears (MDAEs), 33 MD-healthy ears (MDHEs), and 45 HC ears, the angle between the superior and lateral semicircular canals (LSCs) and the angle between the superior and posterior semicircular canals (PSCs) were larger in the MDAE and MDHE groups than the HC group (P<0.01), while the angle between the posterior and LSCs was smaller in the MDAE group than the HC group (P<0.001). The angles between the superior and PSCs and coronal plane (CP) of the coordinate system were significantly smaller in the MDAE and MDHE groups than the HC group (P<0.01); however, the angles between the LSC and axial plane and CP were significantly larger in the MDAE and MDHE groups than the HC group (P<0.001). Conclusions: Spatial position changes in the semicircular canals may be the anatomical basis of MD.

Exploring geometry of genome space via Grassmann manifolds.

It is important to understand the geometry of genome space in biology. After transforming genome sequences into frequency matrices of the chaos game representation (FCGR), we regard a genome sequence as a point in a suitable Grassmann manifold by analyzing the column space of the corresponding FCGR. To assess the sequence similarity, we employ the generalized Grassmannian distance, an intrinsic geometric distance that differs from the traditional Euclidean distance used in the classical k-mer frequency-based methods. With this method, we constructed phylogenetic trees for various genome datasets, including influenza A virus hemagglutinin gene, Orthocoronavirinae genome, and SARS-CoV-2 complete genome sequences. Our comparative analysis with multiple sequence alignment and alignment-free methods for large-scale sequences revealed that our method, which employs the subspace distance between the column spaces of different FCGRs (FCGR-SD), outperformed its competitors in terms of both speed and accuracy. In addition, we used low-dimensional visualization of the SARS-CoV-2 genome sequences and spike protein nucleotide sequences with our methods, resulting in some intriguing findings. We not only propose a novel and efficient algorithm for comparing genome sequences but also demonstrate that genome data have some intrinsic manifold structures, providing a new geometric perspective for molecular biology studies.

Expert consensus on the multidisciplinary diagnosis and treatment of multiple ground glass nodule-like lung cancer (2024 Edition).

ABSTRACT: This expert consensus reviews current literature and provides clinical practice guidelines for the diagnosis and treatment of multiple ground glass nodule-like lung cancer. The main contents of this review include the following: ① follow-up strategies, ② differential diagnosis, ③ diagnosis and staging, ④ treatment methods, and ⑤ post-treatment follow-up.

Development and validation of dietary depression index in Chinese adults.

Objective: Previous studies have suggested diet was associated with depressive symptoms. We aimed to develop and validate Dietary Depression Index (DDI) based on dietary prediction of depression in a large Chinese cancer screening cohort.Methods: In the training set (n = 2729), we developed DDI by using intake of 20 food groups derived from a food frequency questionnaire to predict depression as assessed by Patient Health Questionnaire-9 based on the reduced rank regression method. Sensitivity, specificity, positive predictive value, and negative predictive value were used to assess the performance of DDI in evaluating depression in the validation dataset (n = 1176).Results: Receiver operating characteristic analysis was constructed to determine the best cut-off value of DDI in predicting depression. In the study population, the DDI ranged from -3.126 to 1.810. The discriminative ability of DDI in predicting depression was good with the AUC of 0.799 overall, 0.794 in males and 0.808 in females. The best cut-off values of DDI for depression prediction were 0.204 overall, 0.330 in males and 0.034 in females. DDI was a validated method to assess the effects of diet on depression.Conclusion: Among individual food components in DDI, fermented vegetables, fresh vegetables, whole grains and onions were inversely associated, whereas legumes, pickled vegetables and rice were positively associated with depressive symptoms.

Glutamine metabolic competition drives immunosuppressive reprogramming of intratumour GPR109A+ myeloid cells to promote liver cancer progression.

OBJECTIVE: The metabolic characteristics of liver cancer drive considerable hurdles to immune cells function and cancer immunotherapy. However, how metabolic reprograming in the tumour microenvironment impairs the antitumour immune response remains unclear. DESIGN: Human samples and multiple murine models were employed to evaluate the correlation between GPR109A and liver cancer progression. GPR109A knockout mice, immune cells depletion and primary cell coculture models were used to determine the regulation of GPR109A on tumour microenvironment and identify the underlying mechanism responsible for the formation of intratumour GPR109A+myeloid cells. RESULTS: We demonstrate that glutamine shortage in liver cancer tumour microenvironment drives an immunosuppressive GPR109A+myeloid cells infiltration, leading to the evasion of immune surveillance. Blockade of GPR109A decreases G-MDSCs and M2-like TAMs abundance to trigger the antitumour responses of CD8+ T cells and further improves the immunotherapy efficacy against liver cancer. Mechanistically, tumour cells and tumour-infiltrated myeloid cells compete for glutamine uptake via the transporter SLC1A5 to control antitumour immunity, which disrupts the endoplasmic reticulum (ER) homoeostasis and induces unfolded protein response of myeloid cells to promote GPR109A expression through IRE1α/XBP1 pathway. The restriction of glutamine uptake in liver cancer cells, as well as the blockade of IRE1α/XBP1 signalling or glutamine supplementation, can eliminate the immunosuppressive effects of GPR109A+ myeloid cells and slow down tumour progression. CONCLUSION: Our findings identify the immunometabolic crosstalk between liver cancer cells and myeloid cells facilitates tumour progression via a glutamine metabolism/ER stress/GPR109A axis, suggesting that GPR109A can be exploited as an immunometabolic checkpoint and putative target for cancer treatment.

Treatment techniques and resource recovery of source-separated urine: a bibliometric analysis and literature review.

Human urine, which is high in nutrients, acts as a resource as well as a contaminant. Indiscriminate urine discharge causes environmental pollution and wastes resources. To elucidate the research status and developmental trajectory of source-separated urine (SSU) treatment and recovery, this study was based on the Web of Science Core Collection (WOSCC) database and used the bibliometric software VOSviewer and CiteSpace to conduct a comprehensive and in-depth bibliometric analysis of the related literature in this field. The findings revealed a general upward trend in SSU treatment and recovery from 2000 to 2023. The compendium of 894 scholarly articles predominantly focused on the disciplines of Environmental Sciences, Environmental Engineering, and Water Resources. China and the USA emerged as the foremost contributors. Keyword co-occurrence mapping, clustering, and burst analysis have shown that the recovery of nitrogen and phosphorus from urine is currently the main focus, with future prospects leaning toward the retrieval of biochemicals and chemical energy. This study systematically categorizes and compares the developmental status, current advancements, and research progress in this field. The findings of this study provide a valuable reference for understanding developmental pathways in this field of research.

Influence of FexOy and Al2O3 Contents on the Thermal Stability of Iron Ore-Waste Fibers: Key Mechanisms and Control.

Traditional rock wool fibres are susceptible to crystallization and pulverization. To mitigate this, glass fibres were produced from iron ore waste (IOW). When the ratio of Fe2+ and Fe3+ is 1:3 and the Al2O3 content is 10 wt.%, increasing the FexOy content enhances the thermal stability.At an FexOy content of 17-19% and an Al2O3 content of 10-13%, the glass transition temperature (Tg) peaked. Increasing the FexOy content from 10% to 20% enhanced the stability of Si-O and Al-O bonds and increased bridged oxygen, stabilizing the structure. Here, Fe2+ balances structural charges, while Fe3+ replaces some Al atoms in the network. When the Al2O3 content is 10-13% and the FexOy content is 17-19%, the thermal stability of the IOW rock glass reaches its optimal level. At 20% FexOy content, the structure becomes three-dimensional and cyclic, increasing polymerization. Consequently, incorporating FexOy alongside a 10% Al2O3 content improves thermal stability, supporting the development of high-stability rock wool from IOW. This approach also enhances the refractory properties of rock wool fibres within the FexOy-Al2O3-SiO2-MgO-CaO system.

Association between Lifestyle Modification and All-Cause, Cardiovascular, and Premature Mortality in Individuals with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: This study is designed to explore the correlation between multiple healthy lifestyles within the framework of "lifestyle medicine", and the mortality risk of nonalcoholic fatty liver disease (NAFLD). METHODS: The National Health and Nutrition Examination Survey (NHANES) database was employed. The analysis consisted of 5542 participants with baseline NAFLD and 5542 matched non-NAFLD participants from the database. Lifestyle information, including five low risk factors advocated by lifestyle medicine (healthy diet, vigorous physical activity, healthy sleep duration, avoiding smoking, and maintaining a non-depressed psychological status), was collected through a baseline questionnaire. Cox proportional hazards regression models and Kaplan-Meier survival curve were used to evaluate risk of mortality. In addition, subgroups were analyzed according to gender, age, body mass index and waist circumference. RESULTS: In total, 502 deaths (n = 181 deaths from cardiovascular disease (CVD)) were recorded among NAFLD participants after the median follow up duration of 6.5 years. In the multivariate-adjusted model, compared to participants with an unfavorable lifestyle (scoring 0-1), NAFLD participants with a favorable lifestyle (scoring 4-5) experienced a 56% reduction in all-cause mortality and a 66% reduction in CVD mortality. Maintaining an undepressed psychological state and adhering to vigorous exercise significantly reduced CVD mortality risk in NAFLD participants (HR, 0.64 [95% CI, 0.43-0.95]; HR, 0.54 [95% CI, 0.33-0.88]) while maintaining healthy sleep reduced premature mortality due to CVD by 31%. CONCLUSIONS: Healthy lifestyle, characterized by maintaining an undepressed mental state and healthy sleep, significantly mitigates the risk of all-cause, CVD, and premature mortality risk among NAFLD patients, with a particularly pronounced effect observed in female and obese subpopulations.

Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population: An integrated genomic and transcriptional analysis.

Objective: The clinical significance of homologous recombination deficiency (HRD) in breast cancer, ovarian cancer, and prostate cancer has been established, but the value of HRD in non-small cell lung cancer (NSCLC) has not been fully investigated. This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care. Methods: A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled. HRD status was assessed using the AmoyDx Genomic Scar Score (GSS), with a score of ≥50 considered HRD-positive. Genomic, transcriptomic, tumor microenvironmental characteristics and prognosis between HRD-positive and HRD-negative patients were analyzed. Results: Of the patients, 25.1% (89/355) were HRD-positive. Compared to HRD-negative patients, HRD-positive patients had more somatic pathogenic homologous recombination repair (HRR) mutations, higher tumor mutation burden (TMB) (P<0.001), and fewer driver gene mutations (P<0.001). Furthermore, HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes, MET and MYC in epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutant NSCLC, and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC. HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity. HRD-negative NSCLC showed activated signatures of major histocompatibility complex (MHC)-II, interferon (IFN)-γ and effector memory CD8+ T cells. HRD-positive patients had a worse prognosis and shorter progression-free survival (PFS) to targeted therapy (first- and third-generation EGFR-TKIs) (P=0.042). Additionally, HRD-positive, EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens. Conclusions: Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC. Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC. This study highlights potential actionable alterations in HRD-positive NSCLC, suggesting possible combinational therapeutic strategies for these patients.