Allergic fungal rhinosinusitis linked to other hyper-IgE syndromes through defective TH17 responses.

BACKGROUND: In a gene expression analysis comparing sinus mucosa samples from allergic fungal rhinosinusitis (AFRS) patients with samples from non-AFRS chronic rhinosinusitis with nasal polyp (CRSwNP) patients, the antimicrobial peptide (AMP) histatin 1 (HTN1) was found to be the most differentially downregulated gene in AFRS. OBJECTIVE: We sought to identify the molecular etiology of the downregulated expression of HTN1. METHODS: We used RT-PCR to compare the expression of AMPs and a fungistasis assay to evaluate the antifungal activity of sinus secretions. Using flow cytometry, we characterized the presence of TH17/TH22 cells and signal transducer and activator of transcription (STAT) signaling from AFRS patients, non-AFRS CRSwNP patients, and healthy controls. RESULTS: We confirmed decreased expression of AMPs in AFRS sinus mucosa with concordant decrease in antifungal activity in sinus secretions. IL-22 and IL-22-producing T cells were deficient within sinus mucosa of AFRS patients. In vitro studies demonstrated a defect in IL-6/STAT3 signaling critical for TH17/TH22 differentiation. Epithelial cells from AFRS patients could express AMPs when stimulated with exogenous IL-22/IL-17 and circulating TH17 cell abundance was normal. CONCLUSIONS: Similar to other hyper-IgE syndromes, but distinct from CRSwNP, AFRS patients express a defect in STAT3 activation limited to IL-6-dependent STAT3 phosphorylation that is critical for TH17/TH22 differentiation. This defect leads to a local deficiency of IL-17/IL-22 cytokines and deficient AMP expression within diseased sinus mucosa of AFRS patients. Our findings support evaluation of therapeutic approaches that enhance airway AMP production in AFRS.

Deep evolutionary fusion neural network: a new prediction standard for infectious disease incidence rates.

BACKGROUND: Previously, many methods have been used to predict the incidence trends of infectious diseases. There are numerous methods for predicting the incidence trends of infectious diseases, and they have exhibited varying degrees of success. However, there are a lack of prediction benchmarks that integrate linear and nonlinear methods and effectively use internet data. The aim of this paper is to develop a prediction model of the incidence rate of infectious diseases that integrates multiple methods and multisource data, realizing ground-breaking research. RESULTS: The infectious disease dataset is from an official release and includes four national and three regional datasets. The Baidu index platform provides internet data. We choose a single model (seasonal autoregressive integrated moving average (SARIMA), nonlinear autoregressive neural network (NAR), and long short-term memory (LSTM)) and a deep evolutionary fusion neural network (DEFNN). The DEFNN is built using the idea of neural evolution and fusion, and the DEFNN + is built using multisource data. We compare the model accuracy on reference group data and validate the model generalizability on external data. (1) The loss of SA-LSTM in the reference group dataset is 0.4919, which is significantly better than that of other single models. (2) The loss values of SA-LSTM on the national and regional external datasets are 0.9666, 1.2437, 0.2472, 0.7239, 1.4026, and 0.6868. (3) When multisource indices are added to the national dataset, the loss of the DEFNN + increases to 0.4212, 0.8218, 1.0331, and 0.8575. CONCLUSIONS: We propose an SA-LSTM optimization model with good accuracy and generalizability based on the concept of multiple methods and multiple data fusion. DEFNN enriches and supplements infectious disease prediction methodologies, can serve as a new benchmark for future infectious disease predictions and provides a reference for the prediction of the incidence rates of various infectious diseases.

Anti-inflammatory effect of Trichospira verticillata via suppression of the NLRP3 inflammasome in neutrophilic asthma.

Trichospira verticillata is an annual herb that belongs to the family Asteraceae. Trichospira verticillata extract (TVE) elicits anti-plasmodial activity; however, there has been no detailed report about its anti-inflammatory effects and molecular mechanisms. In addition, herbal plants exhibit anti-inflammatory effects by suppressing the NLRP3 inflammasome. Therefore, the primary goal of this study was to examine the effects of TVE on NLRP3 inflammasome activation by measuring interleukin-1ß (IL-1ß) secretion. We treated lipopolysaccharides (LPS)-primed J774A.1 and THP-1 cells with TVE, which attenuated NLRP3 inflammasome activation. Notably, TVE did not affect nuclear factor-kappa B (NF-κB) signalling or intracellular reactive oxygen species (ROS) production and potassium efflux, suggesting that it inactivates the NLRP3 inflammasome via other mechanisms. Moreover, TVE suppressed the formation of apoptosis-associated speck-like protein (ASC) speck and oligomerization. Immunoprecipitation data revealed that TVE reduced the binding of NLRP3 to NIMA-related kinase 7 (NEK7), resulting in reduced ASC oligomerization and speck formation. Moreover, TVE alleviated neutrophilic asthma (NA) symptoms in mice. This study demonstrates that TVE modulates the binding of NLPR3 to NEK7, thereby reporting novel insights into the mechanism by which TVE inhibits NLRP3 inflammasome. These findings suggest TVE as a potential therapeutic of NLRP3 inflammasome-mediated diseases, particularly NA.

Systematic Analysis of the MIO-forming Residues of Aromatic Ammonia Lyases.

Aromatic ammonia lyases (AALs) and tyrosine/phenylalanine ammonia mutases (TAM/PAM) are 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO)-dependent enzymes. Usually, the MIO moiety is autocatalytically formed from the tripeptide Ala-Ser-Gly (ASG) and acts as an electrophile during the enzymatic reaction. However, the MIO-forming residues (ASG) have some diversity in this enzyme class. In this work, a systematic investigation on the variety of MIO-forming residues was carried out using in-depth sequence analyses. Several protein clusters of AAL-like enzymes with unusual MIO-forming residues such as ACG, TSG, SSG, and CSG were identified, including two novel histidine ammonia lyases and one PAM with CSG and TSG residues, respectively, as well as three novel ergothioneine trimethylammonia lyases without MIO motif. The mutagenesis of common MIO-groups confirmed the function of these MIO variants, which provides good starting points for future functional prediction and mutagenesis research of AALs.

Orthogonality of non-coaxial Laguerre-Gaussian beams.

The conventional orthogonality of Laguerre-Gaussian (LG) beams is widely recognized and serves as the fundamental basis for mode division multiplexing utilizing LG beams as channels. However, this conventional orthogonality holds true only when two LG beams share the same axis. Whether non-coaxial LG beams, with parallel axes separated by a distance, are orthogonal to each other remains an open question. To address this issue and reveal the orthogonality of non-coaxial LG beams, we analytically derive the projection of one LG beam onto another. This projection exhibits a helical phase and a rotationally symmetric amplitude with dark rings present. These dark rings indicate that two non-coaxial LG beams are indeed orthogonal to each other when their axes are appropriately separated. Furthermore, any pair of non-coaxial LG beams within a set also exhibit orthogonality when their axes are fixed at a certain separation distance. This novel form of orthogonality predicts an innovative compound multiplexing technique that simultaneously combines mode and space, enabling more efficient packing of multiple LG beams within a single transmission aperture while maintaining parallel and closely spaced beam axes.

Visible-Light-Promoted Cascade Coupling of 2-Isocyanonaphthalenes with Elemental Sulfur and Amines to Construct Naphtho[2,1-d]thiazol-2-Amines.

A visible-light-induced strategy has been explored for the synthesis of naphtho[2,1-d]thiazol-2-amines through ortho-C-H sulfuration of 2-isocyanonaphthalenes with elemental sulfur and amines under external photocatalyst-free conditions. This three-component reaction, which utilizes elemental sulfur as the odorless sulfur source, molecular oxygen as the clean oxidant, and visible light as the clean energy source, provides a mild and efficient approach to construct a series of naphtho[2,1-d]thiazol-2-amines. Preliminary mechanistic studies indicated that visible-light-promoted photoexcitation of reaction intermediates consisting of thioureas and DBU might be involved in this transformation.

Visible-Light Photoredox-Catalyzed Difunctionalization of Alkynes with Quinoxalin-2(1H)-Ones, P4S10, and Alcohols.

Visible-light photoredox-catalyzed method has been developed for the synthesis of quinoxalin-2(1H)-one-containing vinyl phosphorodithioates via direct difunctionalization of alkynes with quinoxalin-2(1H)-ones, P4S10 and alcohols. This four-component reaction could be carried out under metal-free and mild conditions, affording a number of quinoxalin-2(1H)-one-containing vinyl phosphorodithioates in moderate to good yields with Z-isomers as the major products. Photocatalytic radical mechanism is proposed based on the results of radical trapping and fluorescence quenching experiments.

Identification of associated risk factors for serological distribution of hepatitis B virus via machine learning models.

BACKGROUND: The provincial-level sero-survey was launched to learn the updated seroprevalence of hepatitis B virus (HBV) infection in the general population aged 1-69 years in Chongqing and to assess the risk factors for HBV infection to effectively screen persons with chronic hepatitis B (CHB). METHODS: A total of 1828 individuals aged 1-69 years were investigated, and hepatitis B surface antigen (HBsAg), antibody to HBsAg (HBsAb), and antibody to B core antigen (HBcAb) were detected. Logistic regression and three machine learning (ML) algorithms, including random forest (RF), support vector machine (SVM), and stochastic gradient boosting (SGB), were developed for analysis. RESULTS: The HBsAg prevalence of the total population was 3.83%, and among persons aged 1-14 years and 15-69 years, it was 0.24% and 4.89%, respectively. A large figure of 95.18% (770/809) of adults was unaware of their occult HBV infection. Age, region, and immunization history were found to be statistically associated with HBcAb prevalence with a logistic regression model. The prediction accuracies were 0.717, 0.727, and 0.725 for the proposed RF, SVM, and SGB models, respectively. CONCLUSIONS: The logistic regression integrated with ML models could helpfully screen the risk factors for HBV infection and identify high-risk populations with CHB.

Theoretical Insights into the Mechanism and Origin of Solvent-Dependent Selectivity in the Cyclization of Propargyl Alcohols for the Divergent Synthesis of N-Heterocycles.

This study elucidates the mechanisms and principles governing chemoselectivity in synthesizing two distinct N-heterocycles, benzimidazole thiazine and benzothiazole imidazole, through BF3•OEt2-catalyzed cyclization reactions of propargyl alcohols with benzimidazole thiols. Employing density functional theory calculations, we highlight the crucial role of fluorine source in influencing chemoselectivity. In DCM, BF3, as the catalytic center, coordinates with propargyl alcohol's hydroxyl group to form a precursor. Conversely, in DMF, [BF2•DMF]+, formed from DMF and BF3•OEt2, acts as the catalytic center, activating the propargyl alcohol's hydroxyl group. The mechanisms in both solvents involve sequential steps: B-O bond formation, C-O bond cleavage, S-C bond formation, hydrogen atom transfer (HAT), cyclization, and deprotonation. A notable difference is the HAT process: in DCM, it follows a 1,5-HAT process, while in DMF, BF4- formation from DMF and BF3•OEt2 provides a fluorine source and introduces steric hindrance, favoring a 1,6-HAT process and leading to unique chemoselectivity. This pioneering research showcases the impact of DMF on cyclization reactions, offering valuable insights for comprehending and designing reactions driven by fluorine sources. Crucially, our results propose an innovative reaction mechanism featuring lower potential energy surfaces, enhancing our understanding of the intricate interplay among reactants, catalysts, and solvents.

Recent Advances in Synergistic Effect of Nanoparticles and Its Biomedical Application.

The synergistic impact of nanomaterials is critical for novel intracellular and/or subcellular drug delivery systems of minimal toxicity. This synergism results in a fundamental bio/nano interface interaction, which is discussed in terms of nanoparticle translocation, outer wrapping, embedding, and interior cellular attachment. The morphology, size, surface area, ligand chemistry and charge of nanoparticles all play a role in translocation. In this review, we suggest a generalized mechanism to characterize the bio/nano interface, as we discuss the synergistic interaction between nanoparticles and cells, tissues, and other biological systems. Novel perceptions are reviewed regarding the ability of nanoparticles to improve hybrid nanocarriers with homogeneous structures to enhance multifunctional biomedical applications, such as bioimaging, tissue engineering, immunotherapy, and phototherapy.

Choroid plexus and its relations with age-related diseases.

The choroid plexus is composed of epithelial cells situated on the basal layer. The tight junctions between adjacent choroid plexus epithelial cells establish the blood-cerebrospinal fluid barrier. This barrier, in conjunction with the blood-brain barrier, is crucial for the homeostasis of the brain microenvironment. The choroid plexus epithelium secretes cerebrospinal fluid, growth factors, neuropeptides, and lipids into the ventricles and also serves as a gateway for immune cells to enter the brain. The pathophysiology of aging and neurodegenerative diseases remains largely enigmatic, with an increasing body of research linking the choroid plexus to the etiology of these age-related disorders. In this review, we summarize the known relationship between the choroid plexus epithelium and age-related diseases, aiming to provide new therapeutic clues for these disorders.

Specific emitter identification based on multiple sequence feature learning.

The specific emitter identification is widely used in electronic countermeasures, spectrum control, wireless network security and other civil and military fields. In response to the problems that the traditional specific emitter identification algorithm relies on a priori knowledge and has poor generalizability, and the existing specific emitter identification algorithm based on deep learning has poor feature selection and the adopted feature extraction network is not targeted, etc., the specific emitter identification algorithm based on multi-sequence feature learning is proposed. Firstly, multiple sequence features of the emitted signal of the communication radiation source are extracted, and these features are combined into multiple sequence features. Secondly, the multiple sequence fusion convolutional network is constructed to fuse and deeply extract the multiple sequence features and complete the classification of individual communication radiation sources through the classifier of neural network. The selected sequence features of this algorithm contain more and more essential RFF information, while the targeted design of the multi-sequence feature fusion learning network can effectively extract the essential RFF information. The results show that the algorithm can significantly improve the performance of SEI compared with the benchmark algorithm, with a recognition rate gain of about 17%.

Construction of ß-Oximino Phosphorodithioates via (2,2,6,6-Tetramethylpiperidin-1-yl)oxyl-Promoted Difunctionalization of Alkenes with tert-Butyl Nitrite, P4S10, and Alcohols.

A (2,2,6,6-tetramethylpiperidin-1-yl)oxyl-mediated difunctionalization of alkenes with tert-butyl nitrite, P4S10, and alcohols has been developed for the synthesis of ß-oximino phosphorodithioates. The reaction goes through a radical pathway with the successive installation of phosphorodithioate and an oxime group. This four-component protocol offers a practical approach to constructing a variety of ß-oximino phosphorodithioates in moderate to good yields with favorable functional group tolerance.

Metal-free visible-light-mediated aerobic nitrooxylation for the synthesis of nitrate esters with t-BuONO.

A metal-free and sustainable visible-light-mediated method for the preparation of organic nitrate esters has been developed through the aerobic nitrooxylation reaction of α-diazoesters and cyclic ethers with t-BuONO in the presence of dioxygen. This protocol provides an efficient approach to access nitrate esters with the advantages of clean energy, broad substrate scope, green oxidants, operational simplicity, and mild conditions.

Synergistic Effect of SiO2 and Fe3O4 Nanoparticles in Autophagy Modulation.

Rapid advancements in nanotechnology have expanded its applications and synergistic impact on modern nanosystems. The comprehensive assessment of nanomaterials' safety for human exposure has become crucial and heightened. In addition to the characterization of cell proliferation and apoptosis, probing the implication of autophagy is vital for understanding the ramification of nanomaterials. Hence, HEK-293 kidney cells were employed to understand the changes in induction and perturbation of autophagy in cells by iron oxide (Fe3O4) and silica (SiO2) nanoparticles. Interestingly, Fe3O4 worked as a potent modulator of the autophagy process through its catalytic performance, which can develop better than that of SiO2 nanoparticles mechanism, stressing their therapeutic implication in the understanding of cell behaviors. The quantification of reactive oxygen species (ROS) was measured along with the process of autophagy during cell growth. This modulated autophagy will help in cell fate determination in complementary therapy for disease treatment, provide a clinical strategy for future study.

Platelet-derived major histocompatibility complex class I coating on Treponema pallidum attenuates natural killer cell lethality.

The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum's mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the "pseudo-expression" of MHC class I on the surface of T. pallidum (hereafter referred to a "pseudo-expression" of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.

The complete chloroplast genomes of Polygonatum hunanense, P. verticillatum, and P. caulialatum and their phylogenetic positions.

Polygonatum hunanense H.H. Liu & B.Z. Wang (2021) and P. verticillatum (L.) All. (1875) have been widely used as foods and as folk medicines in China and India, and P. caulialatum S. R. Yi (2021) has recently been described as a new medical plant in China. There is at present a lack of genome information regarding the species. Hence, this study reports the complete chloroplast genomes of the three species. The genomes of P. hunanense, P. verticillatum, and P. caulialatum were 155,583 bp, 155,650 bp, and 155,352 bp in length, respectively. They contained large single-copy (LSC) regions of 84,412 bp, 84,404 bp, and 84,285 bp, small single-copy (SSC) regions of 18,427 bp, 18,416 bp, and 18,463 bp, and a pair of inverted repeats of 26,372 bp, 26,415 bp, and 26,302 bp, respectively. The chloroplast genomes of P. hunanense, P. verticillatum, and P. caulialatum had 133 (103 unique) genes, consisting of 87 protein-coding genes, 38 ribosomal ribonucleic acid (RNA) genes, and eight transfer RNA genes, respectively. A maximum-likelihood phylogenetic tree showed that P. kingianum Coll. et Hemsl. var. grandifolium D.M. Liu & W.Z. Zeng (1991) was closer to P. cyrtonema Hua (1892) rather than to P. kingianum Coll. et Hemsl. (1890), further supporting its status as a unique species of the genus. Moreover, P. verticillatum was separated from the easily confused herb P. cirrhifolium (Wall.) Royle (1839), while P. caulialatum was closest to P. humile Fisch. ex Maxim. (1859). This research provides a foundation for further study of these herbs.

Albumin levels and cerebral collateral circulation in patients with acute ischemic stroke due to intracranial arteriosclerotic: A propensity score-matched analysis.

Cerebral collateral circulation (CC) is associated with the recurrence and severity of acute ischemic stroke (AIS), and early identification of poor CC is helpful for the prevention of AIS. In this study we evaluated the association between serum albumin levels and CC in AIS using logistic regression. Propensity score (PS) matching was used to eliminate the effect of confounders, and restricted cubic splines (RCS) were employed to explore potential nonlinear associations between albumin and CC. In unadjusted logistic regression analysis, lower albumin (OR = 0.85, 95% CI = 0.79-0.92) was associated with poor CC, and after adjusting for covariates, the odds of lower albumin for poor CC compared to good CC were 0.86 (95% CI = 0.79-0.94). In the PS cohort, the association of albumin with CC was consistent with those of the original cohort. RCS results showed a linear relationship between albumin and CC (P values of .006 and .08 for overall and nonlinear associations, respectively). The results of this study suggest that lower serum albumin is independently associated with an increased risk of poor CC, which may serve as an effective predictive indicator for poor CC in patients with severe intracranial atherosclerotic stenosis.

[Effects of Land Use Types on Water Quality at Different Buffer Scales: Tianjin Section of the Haihe River Basin as an Example].

It is important to explore the relationship between land use types and water quality to improve the surface water environment. Based on monthly water quality monitoring data from 16 nationally controlled surface water quality monitoring stations in Tianjin and land use data in 2021, GIS spatial analysis and mathematical and statistical methods were used to study the influence of land use types on surface water quality in buffer zones at different scales. The results showed that:① the land use types in the study area were mainly construction land, farmland, and water areas, which had significant effects on river water quality. Except for water temperature (WT) and pH, the farmland, construction land, and water areas were negatively correlated with each water quality indicator; forest land and grassland were positively correlated with dissolved oxygen (DO) and total nitrogen (TN) and negatively correlated with other water quality indicators. ② The water quality indicators showed obvious spatial differences in different seasons. The pH, DO and TN concentrations were higher in the dry season, whereas the permanganate index, ammonia nitrogen (NH4+-N), and total phosphorus (TP) concentrations were higher in the rainy season. ③ The results of the RDA analysis showed that the 800 m buffer zone land use had the greatest explanatory power for water quality changes in the dry season (50.4%), whereas the 3 000 m buffer zone land use could explain the water quality changes in the rainy season to the greatest extent (49.6%); from the average explanation rate of the dry and rainy seasons, the 3 000 m buffer zone was the best impact scale (50.0%) on water quality indicators in Tianjin. ④ The partial least squares regression (PLSR) analysis showed that the most important variables affecting surface water quality changes were construction land, farmland, and water areas. The predictive ability of the PLSR model of most water quality indicators was stronger in the dry season than that in the rainy season. In the dry season, all water quality indicators, except WT and pH, were most influenced by farmland. In the rainy season, construction land had the greatest influence on WT and NH4+-N concentrations, and the most important influencing factor for the remaining water quality indicators was still farmland. This study showed that the rational planning of land use types within 3 000 m of rivers or lakes was beneficial to improving the water quality of surface water.

Chronobiological perspectives: Association between meal timing and sleep quality.

BACKGROUND: Meal timing has been associated with metabolism and cardiovascular diseases; however, the relationship between meal timing and sleep quality remains inconclusive. OBJECTIVE: This study aims to investigate the relationship between meal timing and sleep quality from a chronobiological perspective. METHODS: This study utilized data from the NHANES for the years 2005-2008, including a cohort of 7,023 participants after applying exclusion criteria. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Meal timing was analyzed based on two 24-hour dietary recalls from each individual, considering the timing of the initial and final meals, meal duration, and frequency of meal occasions. Multiple linear regression models and hierarchical analyses were employed to examine the relationship between meal timing and PSQI scores, adjusting for various demographic and habitat covariates. RESULTS: Statistical analysis revealed a positive correlation between delayed meal timings, increased meal occasions, and elevated PSQI scores, indicating that later meal timing are intricately linked with diminished sleep quality. Both later meal timings and more frequent meal occasions were significantly associated with poorer sleep quality. Compared to the first tertile, the ß (95%CI) values of the third tertile were 0.545 (0.226, 0.864) for first meal timing, 0.586 (0.277, 0.896) for midpoint meal timing, 0.385 (0.090, 0.680) for last meal timing, and 0.332 (0.021, 0.642) for meal occasions in the adjusted models. CONCLUSION: These findings suggest that late initial, midpoint, and final meal timing, as well as more frequent meal occasions, are chrono-nutrition patterns associated with poor sleep quality.