Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis.

JOURNAL/nrgr/04.03/01300535-202502000-00029/figure1/v/2024-05-28T214302Z/r/image-tiff Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis. Human-induced pluripotent stem cell-derived neural stem cell exosomes (hiPSC-NSC-Exos) have shown potential for brain injury repair in central nervous system diseases. In this study, we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism. Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits, enhanced blood-brain barrier integrity, and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage. Additionally, hiPSC-NSC-Exos decreased immune cell infiltration, activated astrocytes, and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and tumor necrosis factor-α post-intracerebral hemorrhage, thereby improving the inflammatory microenvironment. RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion, thereby improving blood-brain barrier integrity. Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects. In summary, our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity, in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

Intestinal flora and inflammatory bowel disease: Causal relationships and predictive models.

Background: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is significantly influenced by intestinal flora. Understanding the genetic and microbiotic interplay is crucial for IBD prediction and treatment. Methods: We used Mendelian randomization (MR), transcriptomic analysis, and machine learning techniques, integrating data from the MiBioGen Consortium and various GWAS datasets. SNPs associated with intestinal flora were mapped to genes, with LASSO regression refining gene selection. Differentially expressed genes (DEGs) and immune infiltration patterns were identified through transcriptomic analysis. Six machine learning models were used for predictive modeling. Findings: MR analysis identified 25 gut microbiota classifications causally related to IBD. SNP mapping and gene expression analysis highlighted 24 significant genes. Drug target MR and colocalization validated these genes' causal relationships with IBD. Key pathways identified included the PI3K-Akt signaling pathway and epithelial-mesenchymal transition. Immune infiltration analysis revealed distinct patterns between high and low LASSO score groups. Machine learning models demonstrated high predictive value, with soft voting enhancing reliability. Interpretation: By integrating MR, transcriptomic analysis, and sophisticated machine learning approaches, this study elucidates the causal relationships between intestinal flora and IBD. The application of machine learning not only enhanced predictive modeling but also offered new insights into IBD pathogenesis, highlighted potential therapeutic targets, and established a robust framework for predicting IBD onset.

UWB-Assisted Bluetooth Localization Using Regression Models and Multi-Scan Processing.

Bluetooth devices have been widely used for pedestrian positioning and navigation in complex indoor scenes. Bluetooth beacons are scattered throughout the entire indoor walkable area containing stairwells, and pedestrian positioning can be obtained by the received Bluetooth packets. However, the positioning performance is sharply deteriorated by the multipath effects originating from indoor clutter and walls. In this work, an ultra-wideband (UWB)-assisted Bluetooth acquisition of signal strength value method is proposed for the construction of a Bluetooth fingerprint library, and a multi-frame fusion particle filtering approach is proposed for indoor pedestrian localization for online matching. First, a polynomial regression model is developed to fit the relationship between signal strength and location. Then, particle filtering is utilized to continuously update the hypothetical location and combine the data from multiple frames before and after to attenuate the interference generated by the multipath. Finally, the position corresponding to the maximum likelihood probability of the multi-frame signal is used to obtain a more accurate position estimation with an average error as low as 70 cm.

Identification and validation of ferroptosis-related biomarkers in intervertebral disc degeneration.

Introduction: Ferroptosis plays a significant role in intervertebral disc degeneration (IDD). Understanding the key genes regulating ferroptosis in IDD could reveal fundamental mechanisms of the disease, potentially leading to new diagnostic and therapeutic targets. Methods: Public datasets (GSE23130 and GSE70362) and the FerrDb database were analyzed to identify ferroptosis-related genes (DE-FRGs) involved in IDD. Single-cell RNA sequencing data (GSE199866) was used to validate the specific roles and expression patterns of these genes. Immunohistochemistry and Western blot analyses were subsequently conducted in both clinical samples and mouse models to assess protein expression levels across different tissues. Results: The analysis identified seven DE-FRGs, including MT1G, CA9, AKR1C1, AKR1C2, DUSP1, CIRBP, and KLHL24, with their expression patterns confirmed by single-cell RNA sequencing. Immunohistochemistry and Western blot analysis further revealed that MT1G, CA9, AKR1C1, AKR1C2, DUSP1, and KLHL24 exhibited differential expression during the progression of IDD. Additionally, the study highlighted the potential immune-modulatory functions of these genes within the IDD microenvironment. Discussion: Our study elucidates the critical role of ferroptosis in IDD and identifies specific genes, such as MT1G and CA9, as potential targets for diagnosis and therapy. These findings offer new insights into the molecular mechanisms underlying IDD and present promising avenues for future research and clinical applications.

Comprehensive pan-cancer analysis of FUTs family as prognostic and immunity markers based on multi-omics data.

BACKGROUND: The dysregulation of fucosyltransferases (FUTs) contributes to alterations in fucosylated epitope expression, which serve as distinctive features of cancer cells. Nonetheless, a comprehensive elucidation of the prognostic biological marker and therapeutic target of the FUTs family in pan-cancer remains elusive. METHODS: Over 10,000 individuals' profiling information was examined, including information on 750 small molecule drugs, 33 types of cancer, and 24 types of immune cells. We focused on POFUT2's function and applied GSVA (Gene Set Variation Analysis) to calculate the FUT score. Survival and cancer pathways were found to be correlated with this score. After deriving a signature via univariate Cox and LASSO regression, we generated and analyzed the ROC curve and developed a nomogram. RESULTS: Our comprehensive analysis revealed epigenetic, genomic, and immunogenomic changes in FUTs, particularly POFUT2, resulting in aberrant expression. Elevated frequencies of CNV (Copy number variation), SNV (Single Nucleotide Variant), and hypermethylation were observed in FUTs. Additionally, the survival of patients with various types of cancers may be predicted by FUT expression. Immune response and prognosis in numerous types of cancer were found to be strongly linked to aberrant POFUT2 expression. Pathway analysis unveiled the role of FUTs in apoptosis, epithelial-to-mesenchymal transition (EMT), cell cycle, DNA damage response, RAS/MAPK, TSC/mTOR, PI3K/AKT, AR, ER, and RTK. A prognostic index for patients diagnosed with adrenocortical carcinoma (ACC) was established by applying a risk model incorporating nine FUTs and based on the findings of the GSVA. CONCLUSIONS: FUTs, particularly POFUT2, emerge as candidate targets for improving the outcomes of immune therapy. The significance of aberrant MUC12 expression, cancer immune therapy, and patient survival in the context of diverse malignancies is enhanced by the strong correlation observed among these factors. Our five-gene risk signature provides patients with ACC with an independent prognostic indicator, emphasizing the critical function of these genes in inhibiting the immune system's response in ACC.

Association of aging related genes and immune microenvironment with major depressive disorder.

OBJECTIVE: To study the relationship between aging related genes (ARGs) and Major Depressive Disorder (MDD). METHODS: The datasets GSE98793, GSE52790 and GSE39653 for MDD were obtained from the GEO database, and ARGs were obtained from the Human Aging Genome Resources database. Differential expression genes (DEGs) screening and GO, KEGG enrichment analysis were performed to uncover the underlying mechanisms. To identify key ARGs associated with MDD (key ARG-DEGs), we employed machine learning methods such as LASSO, SVM, and Random Forest, as well as the plug-ins CytoHubba-MCC and MCODE methods. SsGSEA was used to analyze the immune infiltration of MDD and healthy controls. Furthermore, we created risk prediction nomograms model and ROC curves to assess not only the ability of key ARG-DEGs to diagnose MDD, but also predicted miRNAs and transcription factors (TFs) that might interact. Finally, a two-sample Mendelian randomization (MR) study was performed to confirm the association of identified key ARG-DEGs with depression. RESULTS: DEGs of ARGs between MDD and healthy controls led to the identification of eight ARG-DEGs. GO and KEGG analysis revealed that the pathways associated with these eight ARG-DEGs were primarily concentrated in Foxo pathway, JAK-STAT pathway, Pl3K-AKT pathway, and metabolic diseases. A comprehensive analysis further narrowed down the 8 ARG-DEGs to 4 key ARG-DEGs: MMP9, IL7R, S100B, and EGF. Immune infiltration analysis indicated significant differences in CD8(+) T cells, macrophages, neutrophils, Th2 cells, and TIL cells between MDD and control groups, correlating with these four key ARG-DEGs. Based on these four key ARG-DEGs, a risk prediction model for MDD was developed. The miRNA-TF-mRNA interaction network of the key ARG-DEGs highlights the complexity of the regulatory process, providing valuable insights for future related research. The MR study suggested a potential causal relationship between MMP9 and the risk of depression. CONCLUSION: The process of aging, immune dysregulation, and MDD are closely interconnected. MMP9, IL7R, S100B, and EGF may be used as novel diagnostic biomarkers and potential therapeutic targets for MDD, especially MMP9.

Apolipoprotein A-I: Potential Protection Against Intestinal Injury Induced by Dietary Lipid.

The intestinal barrier system protects the human body from harmful factors, by continuously renewing the intestinal epithelium, tight junctions and enteric microbes. However, dietary fat can harm the intestinal epithelial barrier enhancing gut permeability. In recent years, Apolipoprotein A-I has attracted much attention because of its anti-inflammatory properties. Numerous studies have demonstrated that Apolipoprotein A-I can regulate mucosal immune cells, inhibit the progression of inflammation, promote epithelial proliferation and repair, and maintain physical barrier function; it can also regulate angiogenesis, thereby improving local circulation. This article is intended to elucidate the mechanism by which Apolipoprotein A-I improves intestinal barrier damage caused by dietary fat and to review the role of Apolipoprotein A-I in maintaining intestinal homeostasis.

[Onset of Glycogen Storage Disease Type â « in Two Brothers in the Neonatal Period].

Glycogen storage diseases (GSDs) are a group of autosomal recessive disorders of glucose metabolism.GSDs are caused by congenital deficiency of enzymes in glycogen synthesis or decomposition,which results in glycogen accumulation in organs.According to the types of enzyme deficiency,GSDs can be classified into more than ten types,among which GSD Ⅻ is a super-rare type of GSD.Two brothers with a 5-year age difference presented severe neonatal asphyxia,myasthenia,myocardial damage,anemia,and mental retardation,being GSD Ⅻ homozygous cases with neonatal onset.The results of gene detection showed that nucleotide and amino acid alterations (c.619G>A,p.E207K) of the ALDOA gene existed in the two brothers,being homozygous,and the genotypes in the parents were heterozygous.This article summarized the clinical features,diagnosis,and treatment of GSD Ⅻ,providing reference for exploring the etiology and treatment of severe asphyxia,myasthenia,anemia,and multiple organ damage in neonates after birth.

Meta-Analysis of the Therapeutic Effects of Stem Cell-Derived Extracellular Vesicles in Rodent Models of Hemorrhagic Stroke.

Background: Stem cell-derived extracellular vesicles (SCEVs) have emerged as a potential therapy for hemorrhagic stroke. However, their effects are not fully understood. The aim of this study was to comprehensively evaluate the effects of SCEVs therapy in rodent models of hemorrhagic stroke, including subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH). Materials and Methods: We conducted a comprehensive search of PubMed, EMBASE, and Web of Science until May 2023 to identify studies investigating the effects of SCEVs therapy in rodent models of ICH. The functional outcomes were assessed using neurobehavioral scores. Standardized mean differences (SMDs) and confidence intervals (CIs) were calculated using a random-effects model. Three authors independently screened the articles based on inclusion and exclusion criteria. All statistical analyses were performed using Revman 5.3 and Stata 17.0. Results: Twelve studies published between 2018 and 2023 met the inclusion criteria. Our results showed that SCEVs therapy improved neurobehavioral scores in the rodent SAH model (SMD = -3.49, 95% CI: -4.23 to -2.75; p < 0.001). Additionally, SCEVs therapy improved the chronic neurobehavioral scores of the rodent ICH model (SMD = 2.38, 95% CI: 0.36-4.40; p=0.02) but did not have a significant impact on neurobehavioral scores in the acute and subacute phases. Significant heterogeneity was observed among the studies, and further stratification and sensitivity analyses failed to identify the source of heterogeneity. Conclusions: Our findings suggest that SCEVs therapy may improve neurofunctional behavior after hemorrhagic stroke and provide important insights into the design of preclinical trials.

Improving management in gastroesophageal reflux disease through leveraging WeChat platform for mobile health care: A randomized control trial.

BACKGROUND: Gastroesophageal reflux disease (GERD) refers to a clinical condition characterized by gastric content reflux into the esophagus, causing symptoms like acid regurgitation and heartburn. While patient education is essential for GERD treatment, traditional educational models often struggle to effectively improve treatment outcomes. METHODS: Between January 2021 and April 2022, we enrolled 257 patients and assessed their GERD knowledge. The patients were randomly assigned to either the WeChat group (60 participants) for health education via WeChat platform or the control group (60 participants) for conventional education only. GERD-Q scores were collected at 1, 3, and 6 months post-intervention, with compliance and satisfaction assessed at the study's conclusion. RESULTS: The overall awareness rate of GERD among patients was approximately 22.3 %. The WeChat group showed better compliance than the control group in terms of adhering to a proper diet, taking medication on time, and engaging in moderate exercise (P < 0.05 for all). Furthermore, the WeChat group demonstrated significantly higher treatment effectiveness and satisfaction than the control group (P < 0.05 for all). CONCLUSION: Patients have a relatively low level of knowledge regarding GERD. WeChat has the potential to facilitate lifestyle changes and improve compliance, treatment effectiveness, and treatment satisfaction among patients with gastroesophageal reflux disease.

Comparative analysis of noise and music exposure on inflammatory responses on lipopolysaccharide-induced septic rats.

OBJECTIVE: Environmental factors such as noise and music can significantly impact physiological responses, including inflammation. This study explored how environmental factors like noise and music affect lipopolysaccharide (LPS)-induced inflammation, with a focus on systemic and organ-specific responses. MATERIALS AND METHODS: 24 Wistar rats were divided into four groups (n = 6 per group): Control group, LPS group, noise-exposed group, and music-exposed group. All rats, except for the Control group, received 10 mg/kg LPS intraperitoneally. The rats in the noise-exposed group were exposed to 95 dB noise, and the music-exposed group listened to Mozart's K. 448 music (65-75 dB) for 1 h daily over 7 days. An enzyme-linked immunosorbent assay was utilized to detect the levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), in serum and tissues (lung, liver, and kidney). Western blot examined the phosphorylation levels of nuclear factor-κB (NF-κB) p65 in organ tissues. RESULTS: Compared with the Control group, LPS-induced sepsis rats displayed a significant increase in the levels of TNF-α and IL-1ß in serum, lung, liver, and kidney tissues, as well as a remarkable elevation in the p-NF-κB p65 protein expression in lung, liver, and kidney tissues. Noise exposure further amplified these inflammatory markers, while music exposure reduced them in LPS-induced sepsis rats. CONCLUSION: Noise exposure exacerbates inflammation by activating the NF-κB pathway, leading to the up-regulation of inflammatory markers during sepsis. On the contrary, music exposure inhibits NF-κB signaling, indicating a potential therapeutic effect in reducing inflammation.

Analysis and identification of mRNAsi­related expression signatures via RNA sequencing in lung cancer.

High stemness index scores are associated with poor survival in patients with lung cancer. Studies on the mRNA expression-based stemness index (mRNAsi) are typically conducted using tumor tissues; however, mRNAsi-related expression signatures based on cell-free RNA (cfRNA) are yet to be comprehensively investigated. The present study aimed to elucidate the gene expression profiles of tumor stemness in lung cancer tissues and corresponding cfRNAs in blood, and to assess their links with immune infiltration. Tumor tissue, paracancerous tissue, peripheral blood and lymph node samples were collected from patients with stage I-III non-small cell lung cancer and RNA sequencing was performed. The TCGAbiolinks package was used to calculate the mRNAsi for each of these four types of sample. Weighted gene co-expression network analysis and differentially expressed gene analyses were performed to investigate mRNAsi-related genes, and pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology-based annotation system. In addition, the STAR-Fusion tool was used to detect fusion variants, and CIBERSORT was used to analyze the correlations of stemness signatures in tissues and blood with immune cell infiltration. The mRNAsi values in peripheral blood and lymph nodes were found to be higher than those in cancer tissues. 'Hematopoietic cell lineage' was the only KEGG pathway enriched in mRNAsi-related genes in both lung cancer tissues and peripheral blood. In addition, the protein tyrosine phosphatase receptor type C associated protein gene was the only gene commonly associated with the mRNAsi in these two types of sample. The expression of mRNAsi-related genes was increased in the dendritic and Treg cells in tumor tissues, but was elevated in Treg and CD8 cells in the blood. In conclusion, cfRNAs in the blood exhibit unique stemness signatures that have potential for use in the diagnosis of lung cancer.

A flexible resistive strain gauge with reduced temperature effect via thermal expansion anisotropic composite substrate.

Strain gauge plays vital roles in various fields as structural health monitoring, aerospace engineering, and civil infrastructure. However, traditional flexible strain gauge inevitably brings the pseudo-signal caused by the substrate temperature effect and determines its accuracy. Here, we present an anisotropic composite substrate designed to modify the thermal expansion performance via Micro-electro-mechanical System (MEMS) technology, which facilitates the development of strain gauges that are minimally affected by substrate temperature-induced effect. Compared to the isotropic flexible substrate, the simulated expansion displacement in the thermal insensitive direction is reduced by 53.6% via introducing an anisotropic thermal expansion structure. The developed strain gauge exhibits significantly reduced sensitivity to temperature-induced effect, with a temperature coefficient of resistance decreasing from 87.3% to 10%, along with a notable 47.1% improvement in TCR stability. In addition, the strain gauge displays a sensitivity of 1.99 and boasts a wide strain operational range of 0-6000 µÎµ, while maintaining excellent linearity. Furthermore, stress response conducted on a model of an aircraft wing illustrates the rapid monitoring of the strain gauge, which can detect strain as low as 100 µÎµ. This study strongly highlights the potential applicability of the developed strain gauge in the aircraft, ships, and bridges for monitoring stress.

Influence of surface water and groundwater gradient on spatial distribution of typical vegetation in the hinterland of Taklamakan desert.

Water resources are essential for desert oases and are key drivers of local ecological processes critical to the growth of desert vegetation. In this study, the oasis in the hinterland of the Taklamakan Desert, China, was selected as the research subject. Using high-precision classification of oasis vegetation through machine learning, surface water within the oasis was identified and extracted from multi-year Landsat remote sensing data. The spatial distribution patterns of the main community-building species, Populus euphratica and Tamarix ramosissima, were studied under different moisture gradients using environmental covariates and measured groundwater depth to invert its spatial distribution and K-mean clustering to construct surface water and groundwater moisture gradients. The results indicated that the classification accuracy for the two species reached 0.917. Gradients 1-5 were used to categorize the water resources, dividing surface water and groundwater into five gradients. Gradient 3 exhibited the optimal moisture conditions, with a high surface water distribution frequency (0.017) and shallow groundwater depth (3.158 m), while Gradient 4 showed the least optimal moisture conditions, characterized by a low surface water distribution frequency (0.008) and deep groundwater depth (4.820 m). The water gradient decreased in the following order: Gradient 3 > Gradient 5 > Gradient 1 > Gradient 2 > Gradient 4. The optimum gradients for growth of P. euphratica and T. ramosissima were gradients 5, 1, and 2. The normalized vegetation index spatial distribution patterns of the two species were consistent with that of the moisture gradient. Tamarix ramosissima was found to be more tolerant to salinity and drought than P. euphratica. Overall, this study provides valuable information on the effect of the spatial distribution of water resource gradients on oasis vegetation and can guide future water delivery policies in oases.

Immunosuppressant therapy averts rejection of allogeneic FKBP1A-disrupted CAR-T cells.

Chimeric antigen receptor (CAR) T cells from allogeneic donors promise "off-the-shelf" availability by overcoming challenges associated with autologous cell manufacturing. However, recipient immunologic rejection of allogeneic CAR-T cells may decrease their in vivo lifespan and limit treatment efficacy. Here, we demonstrate that the immunosuppressants rapamycin and tacrolimus effectively mitigate allorejection of HLA-mismatched CAR-T cells in immunocompetent humanized mice, extending their in vivo persistence to that of syngeneic humanized mouse-derived CAR-T cells. In turn, genetic knockout (KO) of FKBP prolyl isomerase 1A (FKBP1A), which encodes a protein targeted by both drugs, was necessary to confer CD19-specific CAR-T cells (19CAR) robust functional resistance to these immunosuppressants. FKBP1AKO 19CAR-T cells maintained potent in vitro functional profiles and controlled in vivo tumor progression similarly to untreated 19CAR-T cells. Moreover, immunosuppressant treatment averted in vivo allorejection permitting FKBP1AKO 19CAR-T cell-driven B cell aplasia. Thus, we demonstrate that genome engineering enables immunosuppressant treatment to improve the therapeutic potential of universal donor-derived CAR-T cells.

Dual inhibition of topoisomerase II and microtubule of podophyllotoxin derivative 5p overcomes cancer multidrug resistance.

Compound 5p is a 4ß-N-substituted podophyllotoxin derivative, which exhibited potent activity toward drug-resistant K562/A02 cells and decreased MDR-1 mRNA expression. Here, we further investigated its detail mechanism and tested its antitumor activity. 5p exerted catalytic inhibition of topoisomerase IIα, and didn't show the inhibitor of topoisomerase I. 5p exhibited the inhibitory effect on microtubule polymerization. 5p showed potent anti-proliferation against breast cancer, oral squamous carcinoma, and their drug-resistant cell lines, with resistance index of 0.61 and 0.86, respectively. 5p downregulated the expression levels of P-gp in KBV200 cells and BCRP in MCF7/ADR cells in dose-dependent manner. Moreover, 5p induced KB and KBV200 cells arrest at G2/M phase by up-regulating the expression of γ-H2AX, p-Histone H3 and cyclin B1. 5p induced apoptosis and pyroptosis by increased the expression levels of cleaved-PARP, cleaved-caspase3, N-GSDME as well as LDH release in KB and KBV200 cells. In addition, 5p efficiently impaired tumor growth in KB and KBV200 xenograft mice. Conclusively, this work elucidated the dual inhibitor of topoisomerase II and microtubule of 5p and its mechanism of overcoming the multidrug resistance, indicating that 5p exerts the antitumor potentiality.

Full-space metasurfaces for independent manipulation of transmission and reflection.

In recent years, beam manipulation using metasurfaces has evolved from being limited to either a transmission or reflection space to encompassing a full space. However, existing methods still inevitably require complex systems and are unable to achieve continuous and arbitrary phase manipulation. Here, one type of a bilayer metasurface is proposed to simultaneously manipulate reflection and transmission phases continuously and independently, which also makes the optical system more compact without requiring any analyzers and enhances the degree of freedom for full-space beam manipulation. As a proof-of-concept demonstration, one device is designed to show different holograms in transmission and reflection spaces. Additionally, the Dammann grating designed in the reflection hologram increases the information capacity. The proposed method may pave the way toward achieving a variety of applications such as multi-channel beam manipulation and multifunctional optical devices.

Integrating enhanced biological phosphorus removal in adsorption-stage to treat real domestic sewage.

Wastewater treatment innovation toward resource recovery facilities raises concerns about the adsorption and bio-degradation (A-B) process. This study integrated enhanced biological phosphorus removal (EBPR) into the A-stage for real domestic sewage treatment using the short sludge retention time (S-SRT) approach. The S-SRT approach resulted in outstanding phosphorus (over 90 %) and COD removal (approximately 88 %), increased sludge yield and organic matter content, and a 1.68-fold increase in energy recovery efficiency by sludge anaerobic digestion. The inhibition of nitrification relieved competition for carbon sources between denitrification and phosphorus removal, allowing for the enrichment of phosphorus-accumulating organisms (PAOs) such as Tetrasphaera and Halomonas, leading to enhanced phosphorus removal activities. Biological adsorption also plays a significant role in achieving steady phosphorus removal performance. This study demonstrates the potential of the S-SRT approach as an effective strategy for simultaneous carbon and phosphorus capture in the A-stage, contributing to energy and nutrient recovery from sewage.

Long-term clinical efficacy of drug-coated balloon angioplasty for TASCII C/D femoropopliteal lesions in older patients with chronic limb-threatening ischemia: A retrospective study.

This study aimed to evaluate the long-term clinical outcomes of drug-coated drug (DCB) angioplasty for long femoropopliteal lesions in older patients with chronic limb-threatening ischemia (CLTI). In this multi-center retrospective study, we enrolled 119 patients with CLTI due to Trans-Atlantic Inter-Society Consensus (TASCII) C/D femoropopliteal lesions who underwent DCB angioplasty. A total of 119 patients with 122 limbs (TASCII C = 67, 54.9%; TASCII D = 55, 45.1%) were enrolled. At 36-month follow-up, primary patency, assisted primary patency, secondary patency, and freedom from target lesion revascularization were 47.3%, 49.8%, 59.5%, and 62.7%, respectively, and there was a significant improvement over baseline in Rutherford class (P < .001) and ankle-brachial index measurements (P < .001). Complex target lesions (P = .017) and 1 stenosis-free outflow vessel (P = .001) were risk predictors of freedom from clinically driven target lesion revascularization. Complex target lesions (P = .044), diabetes (P = .007), and 1 stenosis-free outflow vessel (P = .003) were risk predictors of restenosis. At 2 months, the ulcer healing rate was 96.3% (26/27). At 36 months, the limb salvage and survival rates were 85.8% and 83.3%, respectively. DCB angioplasty were safe and effective for older patients with CLTI attributable to femoropopliteal TASCII C/D lesions.

HIV-MTB Co-Infection Reduces CD4+ T Cells and Affects Granuloma Integrity.

Granuloma is a crucial pathological feature of tuberculosis (TB). The relationship between CD4+ T cells in both peripheral blood and granulomatous tissue, and the integrity of granulomas in Human Immunodeficiency Virus (HIV)-MTB co-infection, remains unexplored. This study collected biopsy specimens from 102 TB patients (53 with HIV-MTB co-infection and 49 only with TB). Hematoxylin and eosin (HE) staining and immunohistochemical staining were performed, followed by microscopic examination of the integrity of tuberculous granulomas. Through statistical analysis of peripheral blood CD4+ T cell counts, tissue CD4+ T cell proportion, and the integrity of granulomas, it was observed that HIV infection leads to poor formation of tuberculous granulomas. Peripheral blood CD4+ T cell counts were positively correlated with granuloma integrity, and there was a similar positive correlation between tissue CD4+ T cell proportions and granuloma integrity. Additionally, a positive correlation was found between peripheral blood CD4+ T cell counts and the proportion of CD4+ T cells in granuloma tissues. Therefore, HIV infection could impact the morphology and structure of tuberculous granulomas, with a reduced proportion of both peripheral blood and tissue CD4+ T lymphocytes.