Transcriptomic analysis reveals molecular characterization and immune landscape of PANoptosis-related genes in atherosclerosis.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease characterized by abnormal lipid deposition in the arteries. Programmed cell death is involved in the inflammatory response of atherosclerosis, but PANoptosis, as a new form of programmed cell death, is still unclear in atherosclerosis. This study explored the key PANoptosis-related genes involved in atherosclerosis and their potential mechanisms through bioinformatics analysis. METHODS: We evaluated differentially expressed genes (DEGs) and immune infiltration landscape in atherosclerosis using microarray datasets and bioinformatics analysis. By intersecting PANoptosis-related genes from the GeneCards database with DEGs, we obtained a set of PANoptosis-related genes in atherosclerosis (PANoDEGs). Functional enrichment analysis of PANoDEGs was performed and protein-protein interaction (PPI) network of PANoDEGs was established. The machine learning algorithms were used to identify the key PANoDEGs closely linked to atherosclerosis. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic potency of key PANoDEGs. CIBERSORT was used to analyze the immune infiltration patterns in atherosclerosis, and the Spearman method was used to study the relationship between key PANoDEGs and immune infiltration abundance. The single gene enrichment analysis of key PANoDEGs was investigated by GSEA. The transcription factors and target miRNAs of key PANoDEGs were predicted by Cytoscape and online database, respectively. The expression of key PANoDEGs was validated through animal and cell experiments. RESULTS: PANoDEGs in atherosclerosis were significantly enriched in apoptotic process, pyroptosis, necroptosis, cytosolic DNA-sensing pathway, NOD-like receptor signaling pathway, lipid and atherosclerosis. Four key PANoDEGs (ZBP1, SNHG6, DNM1L, and AIM2) were found to be closely related to atherosclerosis. The ROC curve analysis demonstrated that the key PANoDEGs had a strong diagnostic potential in distinguishing atherosclerotic samples from control samples. Immune cell infiltration analysis revealed that the proportion of initial B cells, plasma cells, CD4 memory resting T cells, and M1 macrophages was significantly higher in atherosclerotic tissues compared to normal tissues. Spearman analysis showed that key PANoDEGs showed strong correlations with immune cells such as T cells, macrophages, plasma cells, and mast cells. The regulatory networks of the four key PANoDEGs were established. The expression of key PANoDEGs was verified in further cell and animal experiments. CONCLUSIONS: This study evaluated the expression changes of PANoptosis-related genes in atherosclerosis, providing a reference direction for the study of PANoptosis in atherosclerosis and offering potential new avenues for further understanding the pathogenesis and treatment strategies of atherosclerosis.

Analysis of the Influencing Factors of Tumor Volume, Body Immunity, and Poor Prognosis after 125I Particle Therapy for Differentiated Thyroid Cancer.

Objective: To analyze the influencing factors of tumor volume, body immunity, and poor prognosis after 125I particle therapy for differentiated thyroid cancer. Methods: A total of 104 patients with differentiated TC who were treated with 125I particles during January 2020 to January 2021 was picked. These subjects were graded as low-dose group (80Gy-110Gy) and high-dose group (110Gy-140Gy) according to the minimum dose received by 90% of the target volume (D90) after surgery. The tumor volume before and after treatment was compared, and fasting venous blood was collected before and after treatment. The content of thyroglobulin (Tg) was detected by electrochemiluminescence immunoassay. The levels of absolute lymphocyte count (ALC), lymphocytes, neutrophils, and monocytes were detected on automatic blood cell analyzer. The lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ration (PLR) were calculated. The changes in the condition of patients were closely observed, and the occurrence of adverse reactions in the two groups were compared. The risk factors influencing the efficacy of 125I particle therapy for differentiated TC were analyzed through multivariate logistic regression analysis. Results: The total effective rate of patients in the low- and high-dose groups was 78.85% and 82.69%, respectively (P > 0.05). Compared with the pretreatment period, the tumor volume and Tg level in both groups were much lower (P < 0.05), and the differences in tumor volume and Tg level had no statistically significant difference between the two groups before and after treatment (P > 0.05). At 1 week of the treatment, the total incidence of adverse reactions such as nausea, radiation gastritis, radiation parotitis, and neck discomfort was obviously higher in the high-dose group than in the low-dose group (P < 0.05). At 1 month of treatment, the incidence of adverse reactions such as nausea was markedly higher in the high-dose group than in the low-dose group (P < 0.05). After treatment, serum NLR and PLR contents were memorably elevated and LMR level was sharply decreased in both groups, and serum NLR and PLR contents were higher and LMR content was lower in the high-dose group than in the low-dose group (P < 0.05). Multivariate logistic regression analysis showed that the pathological type of follicular adenocarcinoma, tumor size ≥ 2 cm, clinical stage of III~IV, distant metastasis, and high TSH level before 125I particle treatment were all risk factors related to the efficacy of 125I particle treatment of TC (P < 0.05). Conclusion: The efficacy of low-dose and high-dose 125I particles in the treatment of differentiated thyroid cancer is comparable, among which low-dose 125I particles have fewer adverse effects and have less impact on the immunity of the body, which is well tolerated by patients and can be widely used in clinical practice. In addition, the pathological type of follicular adenocarcinoma, tumor size ≥ 2 cm, clinical stage III~IV, distant metastasis, and high TSH level before 125I particle treatment are all risk factors that affect the poor effect of 125I particles on thyroid cancer treatment, and early monitoring of the above index changes can help evaluate the prognosis.

Sulfenate Anion Catalyzed Diastereoselective Synthesis of Aziridines.

Aziridines are highly valued synthetic targets in organic and medicinal chemistry. The organocatalytic synthesis of such structures with broad substrate scope and good diastereoselectivity, however, is rare. Herein, we report a broadly applicable and diastereoselective synthetic method for the synthesis of trans-aziridines from imines and benzylic or alkyl halides utilizing sulfenate anions (PhSO- ) as the catalyst. Substrates bearing heterocyclic aromatic groups, alkyl, and electron-rich and electron-poor aryl groups were shown to be compatible with this method (33 examples), giving good yields and high diastereoselectivities (trans : cis >20 : 1). Further functionalization of aziridines containing cyclopropyl or cyclobutyl groups was achieved through ring-opening reactions, with a cyclobutyl-substituted norephedrine derivative obtained through a four-step synthesis. We offer a mechanistic proposal involving reversible addition of the deprotonated benzyl sulfoxide to the imine to explain the high trans-diastereoselectivity.

A switchable terahertz device combining ultra-wideband absorption and ultra-wideband complete reflection.

Terahertz functional devices have been instrumental in the development of terahertz technology. Moreover, the advent of metamaterials has greatly contributed to the advancement of terahertz devices. However, most of today's metamaterials in the terahertz band exhibit poor performance and are mono-functional. This greatly limits the scalability and application potential of the devices. To achieve diversification and tunability of device functionality, we propose a combination of metamaterial structures and vanadium dioxide film. A metamaterial absorber based on the thermotropic phase change material VO2 has been designed. Flexible switching of absorption performance (complete reflection and ultra-broadband perfect absorption) can be achieved through temperature adjustment. Moreover, the perfectly absorbed bandwidth is a staggering 3.3 THz. The thermal tuning of spectral absorbance has a maximal range of 0.01 to 0.999. The shift in absorption properties is explained by the phase change process of vanadium oxide (MIT). The electric field intensity on the absorber surface at different temperatures was monitored and analysed as a way to correlate the VO2 film phase transition process. The impedance matching theory is applied to explain the high level of absorption generated by the absorber. Finally, the effects of the structural parameters on the performance of the absorber are analysed. This work will have many applications in the terahertz field and offers a wide range of ideas for the design of terahertz-enabled devices.

Thermal tuning of terahertz metamaterial absorber properties based on VO2.

We present a novel, structurally simple, multifunctional broadband absorber. It consists of a patterned vanadium dioxide film and a metal plate spaced by a dielectric layer. Temperature control allows flexible adjustment of the absorption intensity from 0 to 0.999. The modulation mechanism of the absorber stems from the thermogenic phase change properties of the vanadium dioxide material. The absorber achieves total reflection properties in the terahertz band when the vanadium dioxide is in the insulated state. When the vanadium dioxide is in its metallic state, the absorber achieves near-perfect absorption in the ultra-broadband range of 3.7 THz-9.7 THz. Impedance matching theory and the analysis of electric field are also used to illustrate the mechanism of operation. Compared to previous reports, our structure utilizes just a single cell structure (3 layers only), and it is easy to process and manufacture. The absorption rate and operating bandwidth of the absorber are also optimised. In addition, the absorber is not only insensitive to polarization, but also very tolerant to the angle of incidence. Such a design would have great potential in wide-ranging applications, including photochemical energy harvesting, stealth devices, thermal emitters, etc.

Laparoscopic central hepatectomy using a parenchymal-first approach: how we do it.

BACKGROUND: Laparoscopic central hepatectomy (LCH) is a difficult and challenging procedure. This study aimed to describe our experience with LCH using a parenchymal-first approach. METHODS: Between July 2017 and June 2021, 19 consecutive patients underwent LCH using a parenchymal-first approach at our institution. Herein, the details of this procedural strategy are described, and the demographic and clinical data of the included patients were retrospectively analyzed. RESULTS: There were 1 female and 18 male patients, all with hepatocellular carcinoma without major vascular invasion. The mean age was 57 ± 10 years. No patients underwent conversion to open surgery, and no blood transfusions were needed intraoperatively. The average operative duration and the average Pringle maneuver duration were 223 ± 65 min and 58 ± 11 min. respectively. The median blood loss was 200 ml (range: 100-800 ml). Postoperative morbidities occurred in 3 patients (15.8%), including 2 cases of bile leakage and 1 case of acquired pulmonary infection; there were no postoperative complications happened such as bleeding, hepatic failure, or mortality. The average postoperative hospital stay was 10 ± 3 days. CONCLUSION: The optimized procedure of LCH using a parenchymal-first approach is not only feasible but also expected to provide an advantage in laparoscopic anatomical hepatectomy.

The tacrolimus-induced glucose homeostasis imbalance in terms of the liver: From bench to bedside.

Tacrolimus (TAC), the mainstay of maintenance immunosuppressive agents, plays a crucial role in new-onset diabetes after transplant (NODAT). Previous studies investigating the diabetogenic effects of TAC have focused on the ß cells of islets. In this study, we found that TAC contributed to NODAT through directly affecting hepatic metabolic homeostasis. In mice, TAC-induced hypoglycemia rather than hyperglycemia during starvation via suppressing gluconeogenetic genes, suggesting the limitation of fasting blood glucose in the diagnosis of NODAT. In addition, TAC caused hepatic insulin resistance and triglyceride accumulation through insulin receptor substrate (IRS)2/AKT and sterol regulatory element binding protein (SREBP1) signaling, respectively. Furthermore, we found a pivotal role of CREB-regulated transcription coactivator 2 (CRTC2) in TAC-induced metabolic disorders. The restoration of hepatic CRTC2 alleviated the metabolic disorders through its downstream molecules (eg, PCK1, IRS2, and SREBP1). Consistent with the findings from bench, low CRTC2 expression in graft hepatocytes was an independent risk factor for NODAT (odds ratio = 2.692, P = .023, n = 135). Integrating grafts' CRTC2 score into the clinical model could significantly increase the predictive capacity (areas under the receiver operating characteristic curve: 0.71 vs 0.79, P = .048). Taken together, in addition to its impact on pancreatic cells, TAC induces "hematogenous diabetes" via CRTC2 signaling. Liver-targeted management may be of help to prevent or heal TAC-associated diabetes.

The intestinal bacterial community of healthy and diseased animals and its association with the aquaculture environment.

Although increasing levels of attention have been targeted towards aquaculture-associated bacteria, the bacterial community of animal intestines and its relationship with the aquaculture environment need to be further investigated. In this study, we used high-throughput sequencing to analyze the bacterial community of pond water, sediment, and the intestines of diseased and healthy animals. Our data showed that Proteobacteria, Firmicutes, Cyanobacteria, and Bacteroidetes were the dominant taxa of bacteria across all samples and accounted for more than 90% of the total sequence. Difference analysis and Venn diagrams showed that most of the intestinal bacterial OTUs (operational taxonomic units) of diseased and healthy animals were the same as those of sediment and water, indicating that the aquaculture environment was the main source of intestinal bacteria. Compared with healthy animals, a considerable reduction of OTUs was evident in diseased animals. Welch's t test showed that the dominant bacterial taxa in sediment, water, and animal intestine were significantly different (p < 0.05) and each had its own unique dominant microorganisms. In addition, differences between the intestinal bacteria of healthy and diseased animals were represented by potential probiotics and pathogens, such as Bacillus, Vibrio, Oceanobacillus, and Lactococcus. Principal component analysis (PcoA) showed that a similar environment shaped a similar microbial structure. There was a large difference in the spectrum of intestinal bacteria in diseased animals; furthermore, the spectrum of intestinal bacteria in diseased animals was very different from the environment than in healthy animals. This study provides a theoretical basis for a relationship between the intestinal bacteria of healthy and diseased animals and the environment and provides guidance for environmental regulation and disease prevention in aquaculture areas.

Metagenomic Analysis of the Effect of Enteromorpha prolifera Bloom on Microbial Community and Function in Aquaculture Environment.

Enteromorpha prolifera blooms considerably affected coastal environments in recent years. However, the effects of E. prolifera on microbial ecology and function remained unknown. In this study, metagenomic sequencing was used to investigate the effect of E. prolifera bloom on the microbial communities and functional genes in an aquaculture environment. Results showed that E. prolifera bloom could significantly alter the microbial composition and abundance, and heterotrophic bacteria comprised the major groups in the E. prolifera bloom pond, which was dominated by Actinomycetales and Flavobacteriales. The study indicated that viruses played an important role in shaping the microbial community and diversity during E. prolifera bloom. These viruses affected various dominant microbial taxa (such as Rhodobacteraceae, Synechococcus, and Prochlorococcus), which produced an obvious impact on potential nutrient transformation. Functional annotation analysis indicated that E. prolifera bloom would considerably shift the metabolism function by altering the structure and abundance of the microbial community. E. prolifera bloom pond had the low ability of potential metabolic capabilities of nitrogen, sulfur, and phosphate, whereas promoted gene abundance of genetic information processing. These changes in the microbial community and function could produce serious effect on aquaculture ecosystem.

Health-Related Quality of Life in Mandarin-Speaking Children With Cochlear Implants.

OBJECTIVES: The primary aim of this study was to evaluate the health-related quality of life (HRQoL) of children with cochlear implants (CIs) from the parental perspective. The secondary objective was to explore possible relationships between demographic variables (such as age at assessment, gender, age at implantation, and duration of language rehabilitation) and the HRQoL. The third objective was to determine the developmental trajectories of HRQoL. DESIGN: This study included parents of 123 children with CIs (mean age, 40.45 months; mean age of CI implantation, 24.74 months; mean device experience, 16.34 months). The time periods for follow-up were at 0, 1, 2, 3, 6, and 12-month intervals of CI use. The Mandarin Children with Cochlear Implants: Parental Perspectives questionnaire was employed to assess HRQoL. RESULTS: Parents were satisfied with HRQoL, especially with the domain of social relations; however, education received a less positive rating. The duration of CI use was positively correlated with 5 domains, suggesting that children who used CIs for a longer time had higher HRQoL ratings. Children with longer language rehabilitation received more positive ratings in the domains of social relations and education (p < 0.05); children whose mothers had higher education levels received more positive ratings in the domain of general functioning (p < 0.05); children living in cities received more positive ratings in the domains of communication, general functioning and self-reliance (p < 0.05). Girls received more positive rating than boys in the domain of well-being (p < 0.05). No significant correlation was found between age at implantation, age at assessment, only child status, and HRQoL. All domains showed clear increases in the duration of CI use; the majority of the domains showed steeper progress over the first 3 months of CI use. Communication exhibited the most rapid progress, with education progressing at a slower rate. CONCLUSIONS: Parents were satisfied with all domains of HRQoL. Almost all domains exhibited rapid progress over the first 3 months of CI use, with education progressing at a slower rate. This research underscores the importance of language rehabilitation by revealing that strengthening language rehabilitation could be an effective means of improving the HRQoL of children with CIs.

Synthesis of Indoles through Domino Reactions of 2-Fluorotoluenes and Nitriles.

Indoles are essential heterocycles in medicinal chemistry, and therefore, novel and efficient approaches to their synthesis are in high demand. Among indoles, 2-aryl indoles have been described as privileged scaffolds. Advanced herein is a straightforward, practical, and transition-metal-free assembly of 2-aryl indoles. Simply combining readily available 2-fluorotoluenes, nitriles, LiN(SiMe3 )2 , and CsF enables the generation of a diverse array of indoles (38 examples, 48-92 % yield). A range of substituents can be introduced into each position of the indole backbone (C4 to C7, and aryl groups at C2), providing handles for further elaboration.

Palladium-Catalyzed Triarylation of sp3 C-H Bonds in Heteroarylmethanes: Synthesis of Triaryl(heteroaryl)methanes.

A straightforward method for the palladium-catalyzed triarylation of heteroarylmethanes at the methyl group has been developed. The reaction works with a variety of aryl halides, enabling the rapid synthesis of triaryl(heteroaryl)methanes in moderate to excellent yields.

Measurement of HE4 and CA125 and establishment of reference intervals for the ROMA index in the sera of pregnant women.

INTRODUCTION: Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) are biomarkers for ovarian cancer. Their specificity and sensitivity are often limited during pregnancy as a result of great fluctuations. The risk of ovarian malignancy algorithm (ROMA) score, which combines CA125, HE4, and menopausal status, may improve diagnostic performance. There are no reports regarding the ROMA index in pregnant women. Therefore, the aim of our study was to establish appropriate reference intervals (RIs) for the ROMA index in pregnant Chinese women and compare them with those of CA125 and HE4 during pregnancy. METHODS: Serum concentrations of CA125 and HE4 were simultaneously measured in healthy pregnant women via electrochemiluminescence immunoassay (ECLIA). The ROMA index was calculated using premenopausal algorithms. RESULTS: The RIs for the ROMA index calculated by premenopausal algorithms were substantially closer to the normal range in the first 2 trimesters. For pregnant women, the great misclassifications identified in CA125 may be reversed by the use of ROMA index. CONCLUSIONS: We established the RIs for HE4 and CA125, as well as the ROMA index, in pregnant women at different gestational periods. The ROMA index is suggested to be a more promising tumor marker for pregnant women diagnosed with malignance.

Identification and expression analysis of a new invertebrate lysozyme in Kuruma shrimp (Marsupenaeus japonicus).

Lysozyme is an important component of the innate immunity system against invading pathogens. An invertebrate (i-type) lysozyme from the hepatopancreas of Kuruma shrimp Marsupenaeus japonicus (Mj-ilys) was identified. The full-length cDNA of Mj-ilys was 580bp with a 429 bp open reading frame encoding a 142 amino acid polypeptide. The encoded polypeptide was predicted to have a 17 amino acid signal peptide, and a 125 amino acid mature protein with a theoretical mass of 14.099 kDa and an isoelectric point (pI) of 4.18. A Destabilase conserved domain was predicted in Mj-ilys amino acid sequences which may be stable by 10 cysteine residues forming 5 disulfide bonds. Mj-ilys may loss the muramidase and isopeptidase activities due to the lack of the key catalytic residues. Mj-ilys had high homologous of 80-82% with i-type lysozymes of penaeid shrimps. It was first grouped with other i-type lysozyme of shrimps and crabs in a phylogenetic tree predicted by the Neighbor-Joining method. Mj-ilys mRNA was expressed mainly in hepatopancreas and almost undetectable in other tissues. The mRNA expression of Mj-ilys were all found from fertilized eggs to post-larvae of 17 days (PL17), and its expression exhibited significant differences among each developmental stage. After white spot syndrome virus (WSSV) challenge (3.6 × 10(8) virions/µl), the time-dependent expression pattern of Mj-ilys in hepatopancreas and gills showed significantly different. These results indicated that Mj-ilys is potentially involved in the ontogenesis and immune defense in Kuruma shrimp.

Identification and expression analysis of a novel stylicin antimicrobial peptide from Kuruma shrimp (Marsupenaeus japonicus).

Antimicrobial peptides (AMPs) are important components of the innate immune system and function as the first line of defense against invading pathogens. In current study we identified, cloned and characterized a novel stylicin AMP from Kuruma shrimp Marsupenaeus japonicus (Mj-sty). The full-length cDNA of Mj-sty was 428 bp with an open reading frame of 315 bp that encoded 104 amino acids. The theoretical molecular mass of mature Mj-sty was 8.693 kDa with an isoelectric point (pI) of 4.79. A proline-rich N-terminal region and a C-terminal region contained 13 cysteine residues were identified. Genomic sequence analysis with respect to its cDNA showed that Mj-sty was organized into two exons interrupted by one intron. Tissue-specific expression revealed that Mj-sty was mainly transcribed in gills and hemocytes. Expression of Mj-sty in early developmental stages demonstrated that Mj-sty mRNA were present from fertilized eggs to post-larvae of 17 days (PL17), and the expression levels showed a significant variation in different developmental stages. After challenge of white spot syndrome virus (WSSV), the time-dependent expression pattern of Mj-sty in both gills and hepatopancrease showed down-regulation at the early hours of infection, subsequently up-regulation and down-regulation, and then up-regulation at the end hours to almost the half of the controls. The results indicate that Mj-sty is potentially involved in the ontogenesis and immune responses against WSSV.

Anion-dependent assembly of four sensitized near-infrared luminescent heteronuclear Zn(II)-Yb(III) Schiff base complexes from a trinuclear Zn(II) complex.

Four anion-dependent 0D Zn(II)-Yb(III) heterometallic Schiff base complexes, [YbZn2L2(OAc)4]·ClO4 (2), YbZnL2(NO3)3 (3), [(YbL)2(H2O)Cl(OAc)]2·[ZnCl4]2 (4), and YbZnL(OAc)4 (5), were assembled through central metal substitution or reconstruction from homotrinuclear Zn(II) complex {[(Zn(OAc)(H2O)L]2Zn}(ClO4)2·4H2O [1; HL = 2-ethoxy-6-[(pyridin-2-ylmethylimino)methyl]phenol] with different Yb(III)X3 salts [X = ClO4 (2), NO3 (3), Cl (4), and OAc (5)], in which the Zn(II)-sensitized near-infrared luminescent performances in the four complexes 2-5 are closely related to their structural models.

High-Performance All-Textile Triboelectric Nanogenerator toward Intelligent Sports Sensing and Biomechanical Energy Harvesting.

Merging textiles with advanced energy harvesting technology via triboelectric effects brings novel insights into self-powered wearable textile electronics. However, fabrication of a comfortable textile-based triboelectric nanogenerator (TENG) with high outputs remains challenging. Herein, we propose a highly flexible, tailorable, single-electrode all-textile TENG (t-TENG) with both wear comfort and high outputs. A dielectric modulated porous composite coating containing poly(vinylidene fluoride)-hexafluoropropylene copolymer and barium titanate nanoparticles is constructed on conductive fabric to counterpart with highly positive glass fiber fabric through knotted yarn bonding, maintaining the superiority of textiles and strong triboelectricity. Through the synergistic optimization of charge storage via dielectric modulation and charge dissipation offset by electrical poling, remarkable outputs (261 V, 1.5 µA, and 12.7 nC) are obtained from a miniaturized, lightweight t-TENG (2 × 2 cm2, 130 mg) with an instantaneous power density of 654.48 mW·m-2, as well as excellent electrical robustness and device durability over 20,000 cycles. The t-TENG also exhibits a high sensitivity of 3.438 V·kPa-1 in the force region (1-10 N), demonstrating great potential in TENG-based intelligent sports sensing applications for monitoring and correcting the basketball shooting hand and foot arch posture. Furthermore, over 110 light-emitting diode arrays can be lightened up by gently tapping this miniaturized t-TENG. It also offers a wearable power source scheme through integrating the single-electrode device into clothing and utilizing the skin as the grounded electrode, revealing its ease of integration and biomechanical energy harvesting capability. This work provides an attractive paradigm for next-generation textile electronics with well-balanced device performance and wear comfort.

Cytoprotective effects of C1s enzyme in macrophages in atherosclerosis mediated through the LRP5 and Wnt/ß-catenin pathway.

C1s enzyme (active C1s) is a subunit of the complement C1 complex that cleaves low-density lipoprotein receptor-related proteins 5 and 6, leading to Wnt/ß-catenin pathway activation in some cell lines. Macrophages have two major functional polarization states (the classically activated M1 state and the alternatively activated M2 state) and play an essential role in atherosclerosis. An increasing amount of evidence suggests that canonical Wnt signaling is related to macrophage polarization. In this study, we explored the cytoprotective effects of C1s enzyme in macrophages. The results show that C1s enzyme activates canonical Wnt signaling in macrophages, exacerbates macrophage M2 polarization, and inhibits M1 polarization. Moreover, C1s enzyme reduces foam cell formation and simultaneously enhances efferocytosis. This study reveals a novel function of C1s enzyme in macrophages in the context of atherosclerosis.

Algae blooms with resistance in fresh water: Potential interplay between Microcystis and antibiotic resistance genes.

Microcystis, a type of cyanobacteria known for producing microcystins (MCs), is experiencing a global increase in blooms. They have been recently recognized as potential contributors to the widespread of antibiotic resistance genes (ARGs). By reviewing approximately 150 pieces of recent studies, a hypothesis has been formulated suggesting that significant fluctuations in MCs concentrations and microbial community structure during Microcystis blooms could influence the dynamics of waterborne ARGs. Among all MCs, microcystin-LR (MC-LR) is the most widely distributed worldwide, notably abundant in reservoirs during summer. MCs inhibit protein phosphatases or increase reactive oxygen species (ROS), inducing oxidative stresses, enhancing membrane permeability, and causing DNA damage. This further enhances selective pressures and horizontal gene transfer (HGT) chances of ARGs. The mechanisms by which Microcystis regulates ARG dissemination have been systematically organized for the first time, focusing on the secretion of MCs and the alterations of bacterial community structure. However, several knowledge gaps remain, particularly concerning how MCs interfere with the electron transport chain and how Microcystis facilitates HGT of ARGs. Concurrently, the predominance of Microcystis forming the algal microbial aggregates is considered a hotspot for preserving and transferring ARGs. Yet, Microcystis can deplete the nutrients from other taxa within these aggregates, thereby reducing the density of ARG-carrying bacteria. Therefore, further studies are needed to explore the 'symbiotic - competitive' relationships between Microcystis and ARG-hosting bacteria under varied nutrient conditions. Addressing these knowledge gaps is crucial to understand the impacts of the algal aggregates on dynamics of waterborne antibiotic resistome, and underscores the need for effective control of Microcystis to curb the spread of antibiotic resistance. Constructed wetlands and photocatalysis represent advantageous strategies for halting the spread of ARGs from the perspective of Microcystis blooms, as they can effectively control Microcystis and MCs while maintaining the stability of aquatic ecosystem.

Gegen Qinlian decoction ameliorates TNBS-induced ulcerative colitis by regulating Th2/Th1 and Tregs/Th17 cells balance, inhibiting NLRP3 inflammasome activation and reshaping gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine Gegen Qinlian Decoction (GQD) has been clinically shown to be an effective treatment of ulcerative colitis (UC) in China. However, the underlying mechanism of GQD's anti-ulcerative colitis properties and its effect on gut microbiota still deserve further exploration. AIM OF THE STUDY: This study observed the regulatory effects of GQD on Th2/Th1 and Tregs/Th17 cells balance, the NOD-like receptor family pyrin domain containing 3 (NLRP3) infammasome and gut microbiota in TNBS-induced UC in BALB/c mice. MATERIALS AND METHODS: 61 main chemical compounds in the GQD were determined by UPLC-Q-TOF/MS. The UC BALB/c model was established by intrarectal administration of trinitrobenzene sulfonic acid (TNBS), and GQD was orally administered at low and high dosages of 2.96 and 11.83 g/kg/day, respectively. The anti-inflammatory effects of GQD for ulcerative colitis were evaluated by survival rate, body weight, disease activity index (DAI) score, colonic weight and index, spleen index, hematoxylin-eosin (HE) staining and histopathological scores. Flow cytometry was used to detect the percentage of CD4, Th1, Th2, Th17 and Tregs cells. The levels of Th1-/Th2-/Th17-/Tregs-related inflammatory cytokines and additional proinflammatory cytokines (IL-1ß, IL-18) were detected by CBA, ELISA, and RT-PCR. The expressions of GATA3, T-bet, NLRP3, Caspase-1, IL-Iß, Occludin and Zonula occludens-1 (ZO-1) on colon tissues were detected by Western blot and RT-PCR. Transcriptome sequencing was performed using colon tissue and 16S rRNA gene sequencing was performed on intestinal contents. Fecal microbiota transplantation (FMT) was employed to assess the contribution of intestinal microbiota and its correlation with CD4 T cells and the NLRP3 inflammasome. RESULTS: GQD increased the survival rate of TNBS-induced UC in BALB/c mice, and significantly improved their body weight, DAI score, colonic weight and index, spleen index, and histological characteristics. The intestinal barrier dysfunction was repaired after GQD administration through promoting the expression of tight junction proteins (Occludin and ZO-1). GQD restored the balance of Th2/Th1 and Tregs/Th17 cells immune response of colitis mice, primarily inhibiting the increase in Th2/Th1 ratio and their transcription factor production (GATA3 and T-bet). Morever, GQD changed the secretion of Th1-/Th2-/Th17-/Tregs-related cytokines (IL-2, IL-12, IL-5, IL-13, IL-6, IL-10, and IL-17A) and reduced the expressions of IL-1ß, IL-18. Transcriptome results suggested that GQD could also remodel the immune inflammatory response of colitis by inhibiting NOD-like receptor signaling pathway, and Western blot, immunohistochemistry and RT-PCR further revealed that GQD exerted anti-inflammatory effects by inhibiting the NLRP3 inflammasome, such as down-regulating the expression of NLRP3, Caspase-1 and IL-1ß. More interestingly, GQD regulated gut microbiota dysbiosis, suppressed the overgrowth of conditional pathogenic gut bacteria like Helicobacter, Proteobacteria, and Mucispirillum, while the probiotic gut microbiota, such as Lactobacillus, Muribaculaceae, Ruminiclostridium_6, Akkermansia, and Ruminococcaceae_unclassified were increased. We further confirmed that GQD-treated gut microbiota was sufficient to relieve TNBS-induced colitis by FMT, involving the modulation of Th2/Th1 and Tregs/Th17 balance, inhibition of NLRP3 inflammasome activation, and enhancement of colonic barrier function. CONCLUSIONS: GQD might alleviate TNBS-induced UC via regulating Th2/Th1 and Tregs/Th17 cells Balance, inhibiting NLRP3 inflammasome and reshaping gut microbiota, which may provide a novel strategy for patients with colitis.