Prognostic value of oxygen inhalation therapy for simple nocturnal hypoxemia in COPD: a meta-analysis.

Objective: The effect of oxygen therapy on the prognosis of chronic obstructive pulmonary disease (COPD) with nocturnal hypoxemia (NOD) has been controversial. Therefore, this study systematically evaluated the relevant literature and included it into randomized controlled studies for meta-analysis to evaluate the efficacy and prognosis. Methods: We searched PubMed, EMBASE, web of science, Cochrane, China HowNet and Wanfang database for the literature on the prognosis of COPD patients with simple NOD from the establishment of the database to 30 June 2022. The outcome indicators were death and aggravation of the disease. The efficacy evaluation measures were pulmonary function and arterial blood gas results. The publication bias and heterogeneity of the included studies were evaluated. Results: A total of 621 patients from 5 studies were included in this meta-analysis, and there was no publication bias in the included studies. The total mortality of long-term oxygen therapy (LTOT) in COPD patients with simple NOD in oxygen therapy group (RR = 1.04; 95% CI: 0.81-1.33, p = 0.77), mortality (RR = 0.87; 95% CI: 0.58-1.31, p = 0.50), risk of progression to LTOT events (RR = 1.07; 95% CI: 0.76-1.51, p = 0.71). PaO2 in patients with COPD and simple NOD in oxygen therapy group was higher than that in non-oxygen therapy group (mean difference (MD) = 13.47; 95% CI: 3.49-23.46, p = 0.008), the decrease of PaCO2 level was not statistically significant (MD = -10.05; 95% CI: -26.36-6.27, p = 0.23). Conclusion: Oxygen therapy can improve the prognosis of blood oxygen partial pressure in COPD patients with simple NOD, but oxygen therapy has no significant effect on the survival rate, controlling the progression of the disease to LTOT and reducing the partial pressure of carbon dioxide.

The efficacy of steroid-eluting stents on the local inflammation of chronic rhinosinusitis with nasal polyposis after endoscopic sinus surgery: a multicenter prospective longitudinal study.

PURPOSE: Attenuating local inflammation of chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery (ESS) was crucial. Corticosteroids were generally exploited to ameliorate the postoperative state of CRSwNP. This study aims to verify the efficacy of steroid-eluting stents on the local inflammation of CRSwNP following ESS. METHODS: 57 CRSwNP were enrolled from September 2021 to April 2022. 30 were with stents, and 27 were without stents after ESS. Eosinophilic cationic protein (ECP), myeloperoxidase (MPO), eosinophil, and neutrophil levels in nasal secretions, as well as visual analog scale (VAS) and modified perioperative sinus endoscopy (POSE) scores, were assessed preoperatively and after 2, 4, 8, and 12 weeks. RESULTS: All subjects of CRSwNP exhibited reduced results of eosinophil levels, neutrophil levels, nasal obstruction, nasal discharge, loss of smell, and total VAS scores after 12 weeks compared to the preoperative ones (p < 0.05). Compared with control subjects, CRSwNP with stents acquired lower levels of ECP, MPO, loss of smell, total VAS, and POSE scores at four follow-up visits, as well as reduced eosinophil and neutrophil levels in nasal secretions after 12 weeks (p < 0.05). Correlation analysis revealed that postoperative ECP and MPO levels of CRSwNP in nasal secretions correlated strongly with eosinophil and neutrophil levels, respectively, as well as POSE scores (r > 0.6). CONCLUSION: These findings indicated that steroid-eluting stents might be an acclaimed option for CRSwNP in alleviating local inflammation to acquire a superior state after ESS.

Integrative analysis reveals the recurrent genetic etiologies in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is increasingly recognized as a chronic, progressive, and fatal lung disease with an unknown etiology. Current studies focus on revealing the genetic factors in the risk of IPF, making the integrative analysis of genetic variations and transcriptomic alterations of substantial value. AIM: This study aimed to improve the understanding of the molecular basis of IPF through an integrative analysis of whole-exome sequencing (WES), bulk RNA sequencing (RNA-seq), and single-cell RNA sequencing (scRNA-seq) data. METHODS: WES is a powerful tool for studying the genetic basis of IPF, allowing for the identification of genetic variants that may be associated with the development of the disease. RNA-seq data provide a comprehensive view of the transcriptional changes in IPF patients, while scRNA-seq data offer a more granule view of cell-type-specific alterations. RESULTS: In this study, we identified a comprehensive mutational landscape of recurrent genomic and transcriptomic variations, including SNPs, CNVs, and differentially expressed genes, in IPF populations, which may play a significant role in the development and progression of IPF. CONCLUSIONS: Our study provided valuable insights into the genetic and transcriptomic variations associated with IPF, revealing changes in gene expression that may contribute to disease development and progression. These findings highlight the importance of an integrative approach to understanding the molecular mechanisms underlying IPF and may pave the way for identifying potential therapeutic targets.

The early-phase transcriptome and the clinical efficacy analysis in three modes of subcutaneous immunotherapy for allergic rhinitis.

Background: Allergen immunotherapy is the only etiological treatment for allergic rhinitis. Objective: To analyze the efficacy, safety, and mechanism of subcutaneous immunotherapy (SCIT). Methods: The efficacy, safety, and serum immunological changes of 3 modes of subcutaneous immunotherapy were compared. Peripheral blood mononuclear cells (PBMC) transcriptome changes were obtained on the Illumina sequencing platforms. We confirmed differentially expressed genes (DEGs) by quantitative real-time polymerase chain reaction (PCR). The DEGs were analyzed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks. The correlation between the common DEGs and clinical indicators was analyzed by Origin 2022. Results: The 3 SCITs were all effective after 1 year. The Combined Symptom and Medication Score (CSMS) and Visual Analog Score (VAS) in rush immunotherapy (RIT) are lowest after 24 and 48 weeks of treatment among the 3 groups. After treatment, the levels of sIgE, sIgE/tIgE, Th2 cytokines, Th17 cytokines, and percentage of peripheral eosinophils (EOS%) decreased significantly (P＜0.05), while the levels of Th1 type cytokines did not change significantly. Transcriptome analysis identified 24, 24, and 91 DEGs at W3 and 42, 52, 175 DEGs at W7 in conventional immunotherapy (CIT), cluster immunotherapy (CLIT), and RIT groups, respectively. The pathways and functions involved in SCIT include secretion of Th1/2 cytokines, immune cell differentiation. Unlike CIT and CLIT, DEGs are also involved in T cell tolerance induction, T cell anergy, and lymphocyte anergy in RIT. CXCR1, CXCR2, and IER3 had a specific effect on reflecting the improvement of symptoms in allergic rhinitis patients with SCIT. Conclusion: The clinical efficacy of RIT appeared earlier than CIT and CLIT. Clinicians can use the highly conserved gene expression profile to evaluate responses to immunotherapy.

Chromosome-level Dinobdella ferox genome provided a molecular model for its specific parasitism.

BACKGROUND: Dinobdella ferox is the most frequently reported leech species parasitizing the mammalian nasal cavity. However, the molecular mechanism of this special parasitic behavior has remained largely unknown. METHODS: PacBio long-read sequencing, next-generation sequencing (NGS), and Hi-C sequencing were employed in this study to generate a novel genome of D. ferox, which was annotated with strong certainty using bioinformatics methods. The phylogenetic and genomic alterations of D. ferox were then studied extensively alongside the genomes of other closely related species. The obligatory parasitism mechanism of D. ferox was investigated using RNA-seq and proteomics data. RESULTS: PacBio long-read sequencing and NGS yielded an assembly of 228 Mb and contig N50 of 2.16 Mb. Along Hi-C sequencing, 96% of the sequences were anchored to nine linkage groups and a high-quality chromosome-level genome was generated. The completed genome included 19,242 protein-coding genes. For elucidating the molecular mechanism of nasal parasitism, transcriptome data were acquired from the digestive tract and front/rear ends of D. ferox. Examining secretory proteins in D. ferox saliva helped to identify intimate connections between these proteins and membrane proteins in nasal epithelial cells. These interacting proteins played important roles in extracellular matrix (ECM)-receptor interaction, tight junction, focal adhesion, and adherens junction. The interaction between D. ferox and mammalian nasal epithelial cells included three major steps of pattern recognition, mucin connection and breakdown, and repair of ECM. The remodeling of ECM between epithelial cells of the nasal mucosa and epithelial cells of D. ferox may produce a stable adhesion environment for parasitism. CONCLUSIONS: Our study represents the first-ever attempt to propose a molecular model for specific parasitism. This molecular model may serve as a practical reference for parasitism models of other species and a theoretical foundation for a molecular process of parasitism.

A novel fluoropolymer as a protein delivery vector with robust adjuvant effect for cancer immunotherapy.

The inefficient treatment using protein-based nanovaccines is largely attributed to their inadequate immunogenicity. Herein, we developed a novel fluoropolymer (PF) via ring-opening polymerization and constructed a fluoropolymer-based nanovaccine for tumor immunotherapy. Due to the existence of fluoroalkyl chains, PF not only played a crucial role in tumor antigen delivery but also exhibited a remarkable adjuvant effect in enhancing the immunogenicity of nanovaccines. The nanovaccines formed by mixing PF with a model antigen ovalbumin (OVA) enhanced the uptake of antigen proteins by dendritic cells (DCs) and promoted the maturation and antigen presentation of DCs. Compared with free OVA, PF/OVA showed better efficacy in both pre-cancer prevention and tumor treatment. Furthermore, the proportion of CD4+ T and CD8+ T cells was significantly increased in lymph nodes and tumors of mice immunized with PF/OVA. Additionally, there was a great enhancement in the levels of key anti-tumor cytokines (TNF-α and IFN-γ) in the serum of the PF/OVA immunized mice. Our research has shown that fluoropolymer PF applied as a protein vector and adjuvant has great potential for the development of nanovaccines with robust immunogenicity.

The impact of immunoglobulin G N-glycosylation level on COVID-19 outcome: evidence from a Mendelian randomization study.

Background: The coronavirus disease 2019 (COVID-19) pandemic has exerted a profound influence on humans. Increasing evidence shows that immune response is crucial in influencing the risk of infection and disease severity. Observational studies suggest an association between COVID-19 and immunoglobulin G (IgG) N-glycosylation traits, but the causal relevance of these traits in COVID-19 susceptibility and severity remains controversial. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between 77 IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity using summary-level data from genome-wide association studies (GWAS) and applying multiple methods including inverse-variance weighting (IVW), MR Egger, and weighted median. We also used Cochran's Q statistic and leave-one-out analysis to detect heterogeneity across each single nucleotide polymorphism (SNP). Additionally, we used the MR-Egger intercept test, MR-PRESSO global test, and PhenoScanner tool to detect and remove SNPs with horizontal pleiotropy and to ensure the reliability of our results. Results: We found significant causal associations between genetically predicted IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity. Specifically, we observed reduced risk of COVID-19 with the genetically predicted increased IgG N-glycan trait IGP45 (OR = 0.95, 95% CI = 0.92-0.98; FDR = 0.019). IGP22 and IGP30 were associated with a higher risk of COVID-19 hospitalization and severity. Two (IGP2 and IGP77) and five (IGP10, IGP14, IGP34, IGP36, and IGP50) IgG N-glycosylation traits were causally associated with a decreased risk of COVID-19 hospitalization and severity, respectively. Sensitivity analyses did not identify any horizontal pleiotropy. Conclusions: Our study provides evidence that genetically elevated IgG N-glycosylation traits may have a causal effect on diverse COVID-19 outcomes. Our findings have potential implications for developing targeted interventions to improve COVID-19 outcomes by modulating IgG N-glycosylation levels.

Infestation and distribution of chiggers on the Anderson's white-bellied rats in southwest China.

As a group of ectoparasites, chiggers (larvae of chigger mites) are the exclusive vector of scrub typhus (tsutsugamushi disease). Rodents are the most important hosts of chiggers. The Anderson's niviventer rat, Niviventer andersoni, is an endemic species of rodent in China. However, few studies have involved this endemic rodent species and its ectoparasites including chiggers. According to the field investigation in five provincial regions of southwest China between 2001 and 2019, this paper retrospectively analysed the infestation and distribution of chiggers on the body surface of N. andersoni in southwest China for the first time. From 77 Anderson's niviventer rats captured, a total of 527 chiggers were collected and they were identified as 39 species and nine genera in two subfamilies of family Trombiculidae. Of 39 chigger species identified, Leptotrombidium deliense and L. scutellare are the most important vectors of scrub typhus in China. The overall infestation indexes were PM = 29.87%, MA = 6.84 and MI = 22.91, and the indexes of chigger mite community were Mf = 39, H' = 2.60, E = 0.71 and D = 0.12. The dominant chigger species are L. wenense, L. xiaguanense and L. fujianense with a total Cr = 51.04%, among which L. wenense is one of the six main vectors of scrub typhus in China. The dominant chigger species are of aggregated distribution among different individuals of the rats.

Pathogenic Rickettsia, Anaplasma, and Ehrlichia in Rhipicephalus microplus ticks collected from cattle and laboratory hatched tick larvae.

BACKGROUND: The order Rickettsiales contains a group of vector-borne gram-negative obligate intracellular bacteria, which often cause human emerging infectious diseases and economic losses for dairy and meat industries. The purpose of this study is to investigate the distribution of the pathogens including Rickettsia spp., Anaplasma spp., and Ehrlichia spp. in the order Rickettsiales in ticks from Yueyang, a prefecture-level city of Hunan Province in Sothern China, and assess the potentiality of transovarial transmission of these rickettsial organisms. METHODS: Ticks were collected from cattle in a farm in Yueyang City and the tick DNA was used as template to amplify the htrA, rrs, gltA, ompA and ompB genes of Rickettsia as well as rrs and groEL genes of Anaplasma and Ehrlichia. RESULTS: All ticks (465) collected were the cattle tick, Rhipicephalus microplus. PCR showed the minimum infection rate (MIR) was 1.5% (7/465) for Candidatus Rickettsia xinyangensis, 1.9% (9/465) for C. Anaplasma boleense, 1.3% (6/465) for Anaplasma platys, 0.6% (3/465) for A. marginale, and 1.17% (2/465) for each of A. bovis, Ehrlichia minasensis, and a non-classified Ehrlichia sp. A human pathogen, C. Rickettsia xinyangensis and A. platys were detected in 100% (3/3) and 33.3% (2/6) laboratory-hatched larval pools from infected females respectively. CONCLUSION: Our study revealed a diversity of pathogenic rickettsial species in R. microplus ticks from Hunan Province suggesting a threat to people and animals in China. This study also provided the first molecular evidence for the potential transovarial transmission of C. Rickettsia xinyangensis and A. platys in R. microplus, indicating that R. microplus may act as the host of these two pathogens.

Enhanced single-base mutation diversity by the combination of cytidine deaminase with DNA-repairing enzymes in yeast.

The occurrence of random mutations can increase the diversity of the genome and promote the evolutionary process of organisms. High efficiency mutagenesis techniques significantly accelerate the evolutionary process. In this work, we describe a targeted mutagenesis system named MutaT7trans to significantly increase mutation rate and generate mutations across all four nucleotides in yeast. We constructed different DNA-repairing enzyme-PmCDA1-T7 RNA polymerase (T7 RNAP) fusion proteins, achieved targeted mutagenesis by flanking the target gene with T7 promoters, and tuned the mutation spectra by introducing different DNA-repairing enzymes. With this mutagenesis tool, the proportion of non-C â†’ T mutations was 10-11-fold higher than the cytidine deaminase-based evolutionary tools, and the transversion mutation frequency was also elevated. The mutation rate of the target gene was significantly increased to 5.25 × 10-3 substitutions per base (s. p. b.). We also demonstrated that MutaT7trans could be used to evolve the CrtE, CrtI, and CrtYB gene in the ß-carotene biosynthesis process and generate different types of mutations.

A contracting Intertropical Convergence Zone during the Early Heinrich Stadial 1.

Despite the fact that the response of tropical hydroclimate to North Atlantic cooling events during the Heinrich Stadial 1 (HS1) has been extensively studied in African, South American and Indonesia, the nature of such responses remains debated. Here we investigate the tropical hydroclimate pattern over the Indo-Asian-Australian monsoon region during the HS1 by integrating hydroclimatic records, and examining a δ18Oseawater record from Globigerinoides ruber (white) in the tropical Indian Ocean. Our findings indicate that tropical hydrological conditions were synchronously arid in both hemispheres during the early HS1 (~18.3-16.3 ka) in the Indo-Asian-Australian monsoon region, except for a narrow, wet hydrological belt in northern low latitudes, suggesting the existence of a contracted tropical precipitation belt at that time. This study reveals that the meltwater discharge and resulting changes in global temperatures and El Niño exerted a profound influence on the tropical hydroclimate in the Indo-Asian-Australian monsoon region during the early HS1.

Genome engineering on size reduction and complexity simplification: A review.

BACKGROUND: Genome simplification is an important topic in the field of life sciences that has attracted attention from its conception to the present day. It can help uncover the essential components of the genome and, in turn, shed light on the underlying operating principles of complex biological systems. This has made it a central focus of both basic and applied research in the life sciences. With the recent advancements in related technologies and our increasing knowledge of the genome, now is an opportune time to delve into this topic. AIM OF REVIEW: Our review investigates the progress of genome simplification from two perspectives: genome size reduction and complexity simplification. In addition, we provide insights into the future development trends of genome simplification. KEY SCIENTIFIC CONCEPTS OF REVIEW: Reducing genome size requires eliminating non-essential elements as much as possible. This process has been facilitated by advances in genome manipulation and synthesis techniques. However, we still need a better and clearer understanding of living systems to reduce genome complexity. As there is a lack of quantitative and clearly defined standards for this task, we have opted to approach the topic from various perspectives and present our findings accordingly.

Modifying a D-A-π-A-D HTM system for higher hole mobility by the meta-substitution strategy to weaken the electron-donating ability of the donor unit: a DFT study.

Tuning the electron-donating ability (EDA) of the donor units of hole transporting materials (HTMs) is an efficient strategy to modulate the optoelectronic properties of HTMs. Based on this strategy, we first theoretically investigated the effects of the EDA of donor units on D-A-π-A-D architectural HTMs. The results show that the enhanced EDA of the donor unit leads to larger hole reorganization energy and poorer molecular stability of HTMs. In contrast, meta-substitution of side groups is an effective strategy to reduce the EDA of the donor unit. We found that the application of the meta-substitution strategy in the D-A-π-A-D system not only successfully improves the molecular stability, but also achieves higher hole mobility by promoting the electronic coupling between the molecular dimers and decreasing the hole reorganization energies simultaneously. Studies on interfacial properties indicate that intermolecular coupling also synergistically enhances the interfacial charge extraction performance and reduces carrier recombination. In conclusion, by utilizing the meta-substitution strategy to reduce the EDA of donor units on D-A-π-A-D architectural HTMs, we successfully designed four superior performance HTMs mD1, mD2, mD3, and mD4.

The Correlation between Genotype Richness of Submerged Macrophytes and Periphyton Biomass: A Mesocosm Study Based on Five Dominant Submerged Macrophytes from Yangtze River.

Submerged macrophyte and periphyton are main primary producers which strongly interact with each other in clear water shallow lakes. In this study, the effects of genetic variation of the macrophyte species on periphyton biomass were studied in five submerged species. A two-year mesocosm study was conducted with four levels of genetic diversity (1, 4, 8 and 16 genotypes) for each submerged macrophyte, including 1600 individuals and 320 boxes in 20 mesocosms. Of the five submerged species, only Vallisneria spinulosa showed a positive correlation between its levels of genotype richness and the periphyton biomass. The correlation between genetic distance of genotypes and periphyton biomass was tested, which varied with the difference of seasons and species. In summary, we found that in freshwater mesocosms, the genetic diversity of submerged macrophytes may play a role in regulating the periphyton biomass, but the interaction between genetic diversity of macrophytes and periphyton biomass was not straightforward. This study will provide new insights into the interaction dynamics between the two primary producers in shallow lakes.

Effects of dissolved organic matter from sediment and soil samples on the growth and physiology of four bloom-forming algal species.

Algal blooms negatively impact the water quality of reservoirs; however, the role of dissolved organic matter (DOM) in bloom formation in reservoirs has not been investigated. Therefore, we assessed the compositions of sediment- and soil-derived DOM and their effects on the growth, physiology, and photosynthetic activity of Microcystis aeruginosa, Anabaena sp., Chlamydomonas sp., and Peridiniopsis sp. (bloom-forming species). Sediment DOM promoted the growth of all algal species, whereas soil DOM significantly promoted the growth of Chlamydomonas sp. and Peridiniopsis sp.; this effect was due to enhanced stress tolerance and photosynthetic efficiency exhibited by these algae under DOM treatment. However, soil DOM slightly inhibited the growth of Anabaena sp. by increasing reactive oxygen species levels and inactivating some photosystem II reaction centers. The tyrosine-like substance, humic acid-like substances, and unsaturated aliphatic compounds were the main DOM components that affected algal growth. The findings of this study will provide a theoretical foundation for the development of bloom-prevention strategies for river-type reservoirs.

A large particle size is required by a nano/micron sized-fluticasone propionate inhalable suspension for asthma treatment.

The nano/micron sized-fluticasone propionate inhalable suspension (FPs) is used for asthma treatment, and this study aimed to elucidate the effects of particle size on the absorption of FPs by various pulmonary cells and the subsequent therapeutic efficacy for asthma. FPs of 727, 1136 and 1612 nm were prepared, and an increase in diameter diminished the endocytosis and macropinocytosis of FPs by alveolar epithelial cells (A549 and Calu-3 cells) but facilitated their uptake by M2-like macrophages; results about the transport across Calu-3 monolayer showed the mucus layer was the main rate-limiting step for the uptake of FPs by epithelial cells; the animal tests showed that although a decrease in diameter improved the pulmonary absorption of FPs, the particle size did not affect the lung distribution of FPs; a further detection revealed that larger FPs were taken more effectively by alveolar macrophages and lymphocytes and exerted a better therapeutic effect on asthma than the smaller ones. This study showed that the particle size of FPs had a significant impact on their absorption, elimination and cellular distribution in the lung after inhalation and further on their effectiveness in asthma treatment, and the particle size of the nano/micron sized-FPs should be designed and optimized for asthma treatment on the premise of meeting the requirements of inhalation preparations.