Meta-analyzing the mechanism of pyrogenic biochar strengthens nitrogen removal performance in sulfur-driven autotrophic denitrification system: Evidence from metatranscriptomics.

Sulfur-driven autotrophic denitrification (SAD) exhibits significant benefits in treating low carbon/nitrogen wastewater. This study presents an eco-friendly, cost-effective, and highly efficient method for enhancing nitrogen removal performance. The addition of biochar prepared at 300 °C (BC300) notably increased nitrogen removal efficiency by 31.60 %. BC300 concurrently enhanced electron production, the activities of the electron transfer system, and electron acceptors. With BC300, the ratio of NADH/NAD+ rose 2.00±0.11 times compared to without biochar, and the expression of NAD(P)H dehydrogenase genes was markedly up-regulated. In the electron transfer system, BC300 improved the electroactivity of extracellular polymeric substances and the activities of NADH dehydrogenase and complex III in intracellular electron transfer. Subsequently, electrons were directed into denitrification enzymes, where the nar, nir, nor, and nos related genes were highly expressed with BC300 addition. Significantly, BC300 activated the Clp and quorum sensing systems, positively influencing numerous gene expressions and microbial communication. Furthermore, the O%, H%, molar O/C, and aromaticity index in biochar were identified as crucial bioavailable parameters for enhancing nitrogen removal in the SAD process. This study not only confirms the application potential of biochar in SAD, but also advances our comprehension of its underlying mechanisms.

Poly(Glutamic Acid-Lysine) Hydrogels with Alternating Sequence Resist the Foreign Body Response in Rodents and Non-Human Primates.

The foreign body response (FBR) to implanted biomaterials and biomedical devices can severely impede their functionality and even lead to failure. The discovery of effective anti-FBR materials remains a formidable challenge. Inspire by the enrichment of glutamic acid (E) and lysine (K) residues on human protein surfaces, a class of zwitterionic polypeptide (ZIP) hydrogels with alternating E and K sequences to mitigate the FBR is prepared. When subcutaneously implanted, the ZIP hydrogels caused minimal inflammation after 2 weeks and no obvious collagen capsulation after 6 months in mice. Importantly, these hydrogels effectively resisted the FBR in non-human primate models for at least 2 months. In addition, the enzymatic degradability of the gel can be controlled by adjusting the crosslinking degree or the optical isomerism of amino acid monomers. The long-term FBR resistance and controlled degradability of ZIP hydrogels open up new possibilities for a broad range of biomedical applications.

The ERK-cPLA2-ACSL4 axis mediating M2 macrophages ferroptosis impedes mucosal healing in ulcerative colitis.

Ulcerative colitis (UC) is a chronic gastrointestinal disease that can be managed with 5-aminosalicylic acid (5-ASA), the standard treatment for UC. However, the effectiveness of 5-ASA is not always optimal. Our study revealed that despite 5-ASA treatment, cells continued to experience excessive ferroptosis, which may hinder mucosal healing in UC and limit the success of this treatment approach in achieving disease remission. We found that combining 5-ASA with the ferroptosis inhibitor Fer-1 led to a significant inhibition of ferroptosis in macrophages present in the colon tissue, along with an increase in the proportion of M2 macrophages, suggesting that targeting ferroptosis in M2 macrophages could be a potential therapeutic strategy for alleviating UC. Our study also demonstrated that M2 macrophages are more susceptible to ferroptosis compared to M1 macrophages, and this susceptibility is associated with the activated arachidonic acid (AA) metabolism pathway mediated by ERK-cPLA2-ACSL4. Additionally, we found that the expression of cPLA2 gene pla2g4a was increased in the colon of UC patients compared to healthy controls. Furthermore, targeted metabolomics analysis revealed that the combination treatment group, as opposed to the 5-ASA treatment group, exhibited the ability to modulate AA metabolism. Overall, our findings emphasize the importance of addressing macrophage ferroptosis in order to enhance macrophage anti-inflammation, improve mucosal healing, and achieve better therapeutic outcomes for patients with UC.

Alleviated NCOA4-mediated ferritinophagy protected RA FLSs from ferroptosis in lipopolysaccharide-induced inflammation under hypoxia.

OBJECTIVE: Ferroptosis is a reactive oxygen species (ROS)- and iron-dependent form of non-apoptotic cell death process. Previous studies have demonstrated that ferroptosis participates in the development of inflammatory arthritis. However, the role of ferroptosis in rheumatoid arthritis (RA) inflammatory hypoxic joints remains unclear. This study sought to explore the underlying mechanism of ferroptosis on lipopolysaccharide (LPS)-induced RA fibroblast-like synoviocytes (FLSs). METHODS: FLSs, isolated from patients with RA, were treated with LPS and ferroptosis inducer (erastin and RSL-3), and ferroptosis inhibitor (Fer-1 and DFO), respectively. The cell viability was measured by CCK-8. The cell death was detected by flow cytometer. The proteins level were tested by Western blot. The cytosolic ROS and lipid peroxidation were determined using DCFH-DA and C11-BODIPY581/591 fluorescence probes, respectively. The small interfering RNA (siRNA) was used to knock down related proteins. The levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), iron, inflammatory cytokines (IL6 and IL8), and LDH were analyzed by commercial kits. RESULTS: Ferroptosis was activated by LPS in RA FLS with increased cellular damage, ROS and lipid peroxidation, intracellular Fe and IL8, which can be further amplified by ferroptosis inducer (erastin and RSL-3) and inhibited by ferroptosis inhibitor (Fer-1 and DFO). Mechanistically, LPS triggered ferroptosis via NCOA4-mediated ferritinophagy in RA FLSs, and knockdown of NCOA4 strikingly prevent the process of ferroptosis. Intriguingly, LPS-induced RA FLSs became insensitive to ferroptosis and NCOA4-mediated ferritinophagy under hypoxia compared with normoxia. Knockdown of HIF-1α reverted ferroptosis and ferritinophagy evoking by LPS-induced RA FLSs inflammation under hypoxia. In addition, low dose of auranofin (AUR) induced re-sensitization of ferroptosis and ferritinophagy through inhibiting the expression of HIF-1α under hypoxia. CONCLUSIONS: NCOA4-mediated ferritinophagy was a key driver of ferroptosis in inflammatory RA FLSs. The suppression of NCOA4-mediated ferritinophagy protected RA FLSs from ferroptosis in LPS-induced inflammation under hypoxia. Targeting HIF-1α/NCOA4 and ferroptosis could be an effective and valuable therapeutic strategy for synovium hyperplasia in the patients with RA.

Age-Period-Cohort Analysis on Long-Term Mortality Trend of Genitourinary Diseases - China, 1987-2021.

What is already known about this topic?: There has been a lack of attention to genitourinary diseases for an extended period, resulting in limited research on the mortality trends of genitourinary diseases in China. What is added by this report?: This study examines the long-term trend of genitourinary diseases' mortality across Chinese individuals of all genders and in various urban and rural regions. Additionally, it investigates the impact of age-period-cohort effects on this trend. What are the implications for public health practice?: It is imperative to address genitourinary diseases, particularly among vulnerable populations such as rural older men. Policymakers should prioritize these individuals by providing necessary policy interventions and healthcare support.

A Microfluidic System for Detecting Tumor Cells Based on Biomarker Hexaminolevulinate (HAL): Applications in Pleural Effusion.

Malignant pleural effusion is a common clinical problem, which often occurs in cases of malignant tumors, especially in lung cancer. In this paper, a pleural effusion detection system based on a microfluidic chip, combined with specific tumor biomarker, hexaminolevulinate (HAL), used to concentrate and identify tumor cells in pleural effusion was reported. The lung adenocarcinoma cell line A549 and mesothelial cell line Met-5A were cultured as the tumor cells and non-tumor cells, respectively. The optimum enrichment effect was achieved in the microfluidic chip when the flow rates of cell suspension and phosphate-buffered saline achieved 2 mL/h and 4 mL/h, respectively. At the optimal flow rate, the proportion of A549 increased from 28.04% to 70.01% due to the concentration effect of the chip, indicating that tumor cells could be enriched by a factor of 2.5 times. In addition, HAL staining results revealed that HAL can be used to identify tumor cells and non-tumor cells in chip and clinical samples. Additionally, the tumor cells obtained from the patients diagnosed with lung cancer were confirmed to be captured in the microfluidic chip, proving the validity of the microfluidic detection system. This study preliminarily demonstrates the microfluidic system is a promising method with which to assist clinical detection in pleural effusion.

Quality of life profiles and their associations with depressive symptoms and cognitive impairment of community-dwelling older adults in Hong Kong.

Background: This study aimed to (1) explore the quality of life (QoL) profiles of older adults in Hong Kong and (2) examine their association with predictors (age, sex, body mass index, and depressive symptoms) and distal outcome (cognitive impairment) using a person-centered approach. Methods: A total number of 328 community-dwelling older adults in Hong Kong were invited to participate in this study. Data from 259 older adults were identified as valid for the primary analysis. Latent profile analysis was used to explore QoL profiles. Multinomial logistic regression using the R3STEP function in Mplus was used to explore the predictive role of age, sex, body mass index, and depressive symptoms in profile membership. The Bolck-Croon-Hagenaars approach was used to examine how the distal outcome of cognitive impairment differs as a function of QoL profiles. Results: Three QoL profiles emerged from the latent profile analysis (Low, Moderate and High QoL). It was found that depression, but not age, sex, or body mass index, significantly predicted QoL profile membership. The results of the Bolck-Croon-Hagenaars analysis revealed no significant differences in cognitive impairment across the three QoL profiles. Conclusion: This is the first study that examined the relationship between QoL, depressive symptoms and cognitive impairment of older adults using a person-centered approach. The findings provide additional information for the evidence obtained from variable-centered approach on the associations among variables abovementioned. Our additional focus on the antecedents of emergent QoL profiles also provide practical knowledge regarding timely treatment for or prevention of depressive symptoms, which we submit will be crucial for enhancing the QoL of older adults.

Polymers in Engineering Extracellular Vesicle Mimetics: Current Status and Prospective.

The maintenance of a high delivery efficiency by traditional nanomedicines during cancer treatment is a challenging task. As a natural mediator for short-distance intercellular communication, extracellular vesicles (EVs) have garnered significant attention owing to their low immunogenicity and high targeting ability. They can load a variety of major drugs, thus offering immense potential. In order to overcome the limitations of EVs and establish them as an ideal drug delivery system, polymer-engineered extracellular vesicle mimics (EVMs) have been developed and applied in cancer therapy. In this review, we discuss the current status of polymer-based extracellular vesicle mimics in drug delivery, and analyze their structural and functional properties based on the design of an ideal drug carrier. We anticipate that this review will facilitate a deeper understanding of the extracellular vesicular mimetic drug delivery system, and stimulate the progress and advancement of this field.

Recent Advances in Superhydrophobic Surfaces and Applications on Wood.

Superhydrophobic substances were favored in wood protection. Superhydrophobic treatment of wood is of great significance for improving the service life of wood and expanding its application fields, such as improving dimensional stability, durability, UV stability, and reducing wetting. The superhydrophobic phenomenon is attributed to the interaction of micro/nano hierarchical structure and low surface energy substances of the wood surface. This is the common method for obtaining superhydrophobic wood. The article introduces the common preparation methods of superhydrophobic wood material coatings and their mechanisms. These techniques include lithography, sol-gel methods, graft copolymerization, chemical vapor deposition, etc. The latest research progress of superhydrophobic wood material coatings application at domestic and overseas is reviewed, and the current status of superhydrophobic coating application in wood materials and construction is summarized. Finally, superhydrophobic on wood in the field of applied research is presented, and the development trend in the field of functional improvement of wood is foreseen.

Untargeted metabolomics analysis reveals dynamic changes in co-fermentation with human milk-derived probiotics and Poria cocos.

Introduction: To develop functional foods with traditional medicines and homologous food ingredients as well as human milk-derived probiotics, the co-fermentation process of two probiotics, Lactobacillus plantarum R9 and Lactobacillus gasseri B1-27, isolated from the human milk of healthy parturients and the traditional medicine and food homologous ingredient Poria cocos, were separately investigated. Results: The Poria cocos fermentation broth at 2.5% significantly enhanced the total number of L. plantarum R9 (p = 0.001) and L. gasseri B1-27 (p = 0.013) after 20 h of fermentation, and Non-targeted metabolomics assays conducted before and after fermentation of the human milk-derived L. plantarum R9 and L. gasseri B1-27 using the 2.5% Poria cocos fermentation broth revealed 35 and 45 differential metabolites, respectively. A variety of active substances with physiological functions, such as L-proline, L-serine, beta-alanine, taurine, retinol, luteolin, and serotonin, were found to be significantly increased. Mannitol, a natural sweetener with a low glycemic index, was also identified. The most significantly altered metabolic pathways were pyrimidine metabolism, pentose phosphate, yeast meiosis, ABC transporter, insulin signaling, and mineral absorption, suggesting that co-fermentation of human milk-derived probiotics and Poria cocos may affect the metabolism of trace minerals, sugars, organic acids, and amino acids. Discussion: Overall, we determined that the optimal concentration of Poria cocos to be used in co-fermentation was 2.5% and identified more than 35 differentially expressed metabolites in each probiotic bacteria after co-fermentation. Moreover, several beneficial metabolites were significantly elevated as a result of the co-fermentation process indicating the valuable role of Poria cocos as a functional food.

Recent Advances in Mechanical Reinforcement of Zwitterionic Hydrogels.

As a nonspecific protein adsorption material, a strong hydration layer provides zwitterionic hydrogels with excellent application potential while weakening the interaction between zwitterionic units, leading to poor mechanical properties. The unique anti-polyelectrolyte effect in ionic solution further restricts the application value due to the worsening mechanical strength. To overcome the limitations of zwitterionic hydrogels that can only be used in scenarios that do not require mechanical properties, several methods for strengthening mechanical properties based on enhancing intermolecular interaction forces and polymer network structure design have been extensively studied. Here, we review the works on preparing tough zwitterionic hydrogel. Based on the spatial and molecular structure design, tough zwitterionic hydrogels have been considered as an important candidate for advanced biomedical and soft ionotronic devices.

Comparison of structural and antioxidant activity of polysaccharide extracted from truffles.

As the main component of truffles, polysaccharides have a variety of biological activities such as anti-oxidation, anti-tumor, and hypoglycemic activity, and these activities are closely related to its structure. In this study, Tuber Aestivum crude polysaccharide (TACP) and Tuber Melanosporum crude polysaccharide (TMCP) were obtained from Tuber Aestivum and Tuber Melanosporum by using microwave-assisted hot water, and then the Sephadex G-200 column was utilized to further separate and purify Tuber Aestivum polysaccharide (TAP) and Tuber Melanosporum polysaccharide (TMP) from TACP and TMCP. The structural characterization results showed that the molecular weight of TAP was 2.18 × 104  kDa, while TMP was 8.79 × 103  kDa. Although the two polysaccharide components were mainly composed of mannose (Man) and glucose (Glc), the molar ratio of Man and Glc in TAP was 14.76: 12.31, with a molar ratio of 5.43:10.94 in TMP. Furthermore, the antioxidant activity of two polysaccharide components was evaluated. TAP and TMP could protect porcine jejunal epithelial (IPEC-J2) cells from oxidative damage by H2 O2 , but TAP exhibited stronger antioxidant effects. It was mainly reflected that TAP could increase the secretion level of intracellular antioxidant enzymes (superoxide dismutase and catalase) in IPEC-J2 cells, and had a significant effect on the total antioxidant capacity of cells. The reactive oxygen species and malondialdehyde had better scavenging ability at the concentration of 20 µg/ml. The difference between TAP and TMP may be due to the dissimilar structure. Its structure-activity relationship needs further study. PRACTICAL APPLICATION: The structure of TAP and TMP were different, and TAP had higher molecular weight. Besides, TAP and TMP can protect IPEC-J2 cells from oxidative stress, providing a theoretical basis for developing potential antioxidant drugs of practical significance.

Piperlongumine combined with vitamin C as a new adjuvant therapy against gastric cancer regulates the ROS-STAT3 pathway.

OBJECTIVE: To investigate the effects of piperlongumine (PL) and vitamin C (VC) on signal transducer and activator of transcription 3 (STAT3) signalling in gastric cancer cell lines. METHODS: In vivo tumour xenograft anticancer assays were undertaken to confirm the anticancer activity of PL. Cell viability, flow cytometry and Western blot assays were undertaken to evaluate the anticancer effects of PL, VC and combinations of PL and VC in AGS and KATO III cells. RESULTS: Both PL and VC induced apoptosis and inhibited cell proliferation in AGS and KATO III cells. These effects were dependent on reactive oxygen species (ROS). PL effectively suppressed STAT3 activation while VC caused abnormal activation of STAT3. The combination of PL and VC exhibited a stronger apoptotic effect compared with either agent alone. PL reversed the abnormal activation of STAT3 by VC, which could be a key to their synergistic effect. CONCLUSIONS: PL combined with VC exhibited a stronger anticancer effect by regulating the ROS-STAT3 pathway, suggesting that this combination might be a potential adjuvant therapy for gastric cancer.

STAT3/HIF-1α/fascin-1 axis promotes RA FLSs migration and invasion ability under hypoxia.

Rheumatoid arthritis (RA) synovium was identified as "tumor-like" tissues because of the hypoxic microenvironment, significant cell proliferation, and invasion phenotypes. It was reported that hypoxia promoted tumor aggressiveness via up-regulated expression of fascin-1 in cancer. However, the role of fascin-1 in RA synovial hyperplasia and joint injury progression remains unknown. In the current study, we first identified that both fascin-1 and HIF-1α were highly expressed in the RA synovium, in which they were widely colocalized, compared to osteoarthritis(OA). As well, levels of fascin-1 in RA fibroblast-like synoviocytes(FLSs) were found significantly higher than those in OA FLSs. Further, it was demonstrated that the mRNA and protein levels of fascin-1 in RA FLSs were up-regulated in hypoxia (3 % O2) and experimental hypoxia induced by cobalt chloride. Mechanistically, the HIF-1α-mediated hypoxia environment activated the gene expression of the fascin-1 protein, which in turn promoted the migration and invasion of RA FLSs. Accordingly, the restoration of FLSs migration and invasion was observed following siRNA-mediated silencing of fascin-1 and HIF-1α expression. Notably, under the experimental hypoxia, we found that the expression levels of fascin-1, HIF-1α, and p-STAT3 were increased in a time-dependent manner, and fascin-1and HIF-1α expressions were dependent on p-STAT3. Our results indicated that hypoxia-induced fascin-1 up-regulation promoted RA FLSs migration and invasion through the STAT3/HIF-1α/fascin-1 axis, which might represent a novel therapeutic target for the treatment of RA.

Acoustic spatial patterns recognition based on convolutional neural network and acoustic visualization.

In this work, a convolutional neural network (CNN) is applied to recognize acoustic spatial patterns with the aid of acoustic visualization. The acoustic spatial patterns are obtained by the singular value decomposition of an acoustic radiation operator built with the boundary integral equation. It is to explore the powerful capability of the CNN in the image processing by analogously rendering the measured acoustic spatial patterns into images. Due to practical limitations, a higher resolution of an acoustic image is achieved by interpolating the pressure on a coarse grid. Steady-state analysis of acoustic problems is a complex domain problem. The acoustic fields are then supplied into a CNN scheme as two-channel data which are real and imaginary components of the pressure. Random noises and incident waves with varying energy are added to the measured data to simulate influences from uncorrelated and correlated noises, respectively. It is demonstrated that once the CNN scheme is built and trained with adequate data, which is numerically synthesized, the patterns can be more accurately and robustly recognized by comparing it with the cross-correlation based methods. The hierarchical feature representative as well as nonlinear perception makes the proposed method a promising approach for fault diagnosis and condition monitoring based on spatial acoustic measurements.

XAB2 depletion induces intron retention in POLR2A to impair global transcription and promote cellular senescence.

XAB2 is a multi-functional protein participating processes including transcription, splicing, DNA repair and mRNA export. Here, we report POLR2A, the largest catalytic subunit of RNA polymerase II, as a major target gene down-regulated after XAB2 depletion. XAB2 depletion led to severe splicing defects of POLR2A with significant intron retention. Such defects resulted in substantial loss of POLR2A at RNA and protein levels, which further impaired global transcription. Treatment of splicing inhibitor madrasin induced similar reduction of POLR2A. Screen using TMT-based quantitative proteomics identified several proteins involved in mRNA surveillance including Dom34 with elevated expression. Inhibition of translation or depletion of Dom34 rescued the expression of POLR2A by stabilizing its mRNA. Immuno-precipitation further confirmed that XAB2 associated with spliceosome components important to POLR2A expression. Domain mapping revealed that TPR motifs 2-4 and 11 of XAB2 were critical for POLR2A expression by interacting with SNW1. Finally, we showed POLR2A mediated cell senescence caused by XAB2 deficiency. Depletion of XAB2 or POLR2A induced cell senescence by up-regulation of p53 and p21, re-expression of POLR2A after XAB2 depletion alleviated cellular senescence. These data together support that XAB2 serves as a guardian of POLR2A expression to ensure global gene expression and antagonize cell senescence.

XAB2 functions in mitotic cell cycle progression via transcriptional regulation of CENPE.

Xeroderma pigmentosum group A (XPA)-binding protein 2 (XAB2) is a multi-functional protein that plays critical role in processes including transcription, transcription-coupled DNA repair, pre-mRNA splicing, homologous recombination and mRNA export. Microarray analysis on gene expression in XAB2 knockdown cells reveals that many genes with significant change in expression function in mitotic cell cycle regulation. Fluorescence-activated cell scanner analysis confirmed XAB2 depletion led to cell arrest in G2/M phase, mostly at prophase or prometaphase. Live cell imaging further disclosed that XAB2 knockdown induced severe mitotic defects including chromosome misalignment and defects in segregation, leading to mitotic arrest, mitotic catastrophe and subsequent cell death. Among top genes down-regulated by XAB2 depletion is mitotic motor protein centrosome-associated protein E (CENPE). Knockdown CENPE showed similar phenotypes to loss of XAB2, but CENPE knockdown followed by XAB2 depletion did not further enhance cell cycle arrest. Luciferase assay on CENPE promoter showed that overexpression of XAB2 increased luciferase activity, whereas XAB2 depletion resulted in striking reduction of luciferase activity. Further mapping revealed a region in CENPE promoter that is required for the transcriptional regulation by XAB2. Moreover, ChIP assay showed that XAB2 interacted with CENPE promoter. Together, these results support a novel function of XAB2 in mitotic cell cycle regulation, which is partially mediated by transcription regulation on CENPE.