Spatial metabolomics to discover hypertrophic scar relevant metabolic alterations and potential therapeutic strategies: A preliminary study.

Spatially mapping the metabolic remodeling of hypertrophic scar and surrounding normal skin tissues has the potential to enhance our comprehension of scar formation and aid in the advancement of therapeutic interventions. In this study, we employed matrix-assisted laser desorption/ionization (MALDI), a mass spectrometry imaging technique, to visualize the hierarchical distribution of metabolites within sections of hypertrophic scar and surrounding normal skin tissues. A comprehensive analysis identified a total of 1631 metabolites in these tissues. The top four classes that were identified included benzene and substituted derivatives, heterocyclic compounds, amino acids and its metabolites, and glycerophospholipids. In hypertrophic scar tissues, 22 metabolites were upregulated and 66 metabolites were downregulated. MetaboAnalyst pathway analysis indicated that glycerophospholipid metabolism was primarily associated with these altered 88 metabolites. Subsequently, six metabolites were selected, their spatial characteristics were analyzed, and they were individually added to the cell culture medium of primary hypertrophic scar fibroblasts. The preliminary findings of this study demonstrate that specific concentrations of 1-pyrrolidinecarboxamide, 2-benzylideneheptanal, glycerol trioleate, Lyso-PAF C-16, and moxonidine effectively inhibited the expressions of COL1A1, COL1A2, COL3A1, and ACTA2. These bioactive metabolites exhibit mild and non-toxic properties, along with favorable pharmacokinetics and pharmacodynamics, making them promising candidates for drug development. Consequently, this research offers novel therapeutic insights for hypertrophic scar treatment.

Cancer-Associated Fibroblasts Expressing Sulfatase 1 Facilitate VEGFA-Dependent Microenvironmental Remodeling to Support Colorectal Cancer.

Tumor stroma plays a critical role in fostering tumor progression and metastasis. Cancer-associated fibroblasts (CAF) are a major component of the tumor stroma. Identifying the key molecular determinants for the protumor properties of CAFs could enable the development of more effective treatment strategies. In this study, through analyses of single-cell sequencing data, we identified a population of CAFs expressing high levels of sulfatase 1 (SULF1), which was associated with poor prognosis in patients with colorectal cancer. Colorectal cancer models using mice with conditional SULF1 knockout in fibroblasts revealed the tumor-supportive function of SULF1+ CAFs. Mechanistically, SULF1+ CAFs enhanced the release of VEGFA from heparan sulfate proteoglycan. The increased bioavailability of VEGFA initiated the deposition of extracellular matrix and enhanced angiogenesis. In addition, intestinal microbiota-produced butyrate suppressed SULF1 expression in CAFs through its histone deacetylase (HDAC) inhibitory activity. The insufficient butyrate production in patients with colorectal cancer increased the abundance of SULF1+ CAFs, thereby promoting tumor progression. Importantly, tumor growth inhibition by HDAC was dependent on SULF1 expression in CAFs, and patients with colorectal cancer with more SULF1+ CAFs were more responsive to treatment with the HDAC inhibitor chidamide. Collectively, these findings unveil the critical role of SULF1+ CAFs in colorectal cancer and provide a strategy to stratify patients with colorectal cancer for HDAC inhibitor treatment. Significance: SULF1+ cancer-associated fibroblasts play a tumor-promoting role in colorectal cancer by stimulating extracellular matrix deposition and angiogenesis and can serve as a biomarker for the therapeutic response to HDAC inhibitors in patients.

IL-10: the master immunomodulatory cytokine in allergen immunotherapy.

INTRODUCTION: Allergen immunotherapy (AIT) is the only disease-modifying treatment for patients with IgE-mediated allergic diseases. Successful AIT can induce long-term immune tolerance to the common allergen, which provides clinical benefits for years after discontinuation. The cytokine interleukin (IL)-10, as a key anti-inflammatory mediator with strong immunoregulatory functions, has drawn increasing attention over the past decades. AREAS COVERED: After an extensive search of PubMed, EMBASE, and Web of Science databases, covering articles published from 1989 to 2024, our review aims to emphasize the key common information from previous reviews on the crucial involvement of IL-10 in allergen immunotherapy (AIT) induced immunological tolerance. In this review, we discuss the regulation of IL-10 expression and the molecular pathways associated with IL-10 function. We also further summarize mechanisms of immune tolerance induced by AIT, especially the indispensable role of IL-10 in AIT. EXPERT OPINION: IL-10 plays an indispensable role in immune tolerance induced by AIT. Understanding the importance of the role of IL-10 in AIT would help us comprehend the mechanisms thoroughly and develop targeted therapeutics for allergic diseases.

Blood and local eosinophil levels in chronic rhinitis: Observations during seasonal allergen exposure and non-exposure.

Background: Allergic rhinitis (AR) is a typical type 2 inflammatory disease and eosinophils play a critical role of cardinal effectors in type 2 inflammation. However, the distribution of eosinophils in patients with different subtypes of rhinitis and the effect of allergen exposure on them remain understudied. The aim of this study was to investigate the characteristics and factors influencing the distribution of systemic and local eosinophils in patients with non-AR (NAR), perennial AR (PAR), and seasonal AR (SAR), as well as the effect of seasonal allergen exposure levels on eosinophils. Methods: This was a population-based, cross-sectional observational study of consecutive chronic rhinitis (CR) outpatients who volunteered to participate in the survey during the spring pollen season and non-pollen season of 2023 in Beijing. All participants underwent serum allergen testing, blood routine examination, and nasal secretion smear cytology, and completed questionnaires mainly involving basic information, history review, and symptom assessment. Spring pollen dispersal concentration were considered. Results: A total of 558 CR patients eligible for enrollment were collected, including 198 NAR, 204 PAR, and 156 SAR patients. PAR had the highest blood eosinophil levels and the most severe overall nasal and ocular symptoms of SAR. Compared with subjects with blood eosinophil counts <0.3 × 109/L, those with ≥0.3 × 109/L had significantly more severe nasal and ocular symptoms and a significantly higher rate of comorbid asthma and allergic conjunctivitis. Blood eosinophil levels were significantly higher in SAR patients during the pollen season compared to the non-pollen season, and pollen concentrations were positively correlated with systemic and local eosinophil levels. Conclusions: Blood eosinophil levels varied in patients with different subtypes of rhinitis. Patients with high blood eosinophil levels had more severe overall nasal and ocular symptoms, and that blood eosinophils levels were significantly higher in patients with asthma or allergic conjunctivitis than patients without comorbidities. There was a positive trend between allergen exposure and systemic and local eosinophil levels. Further longitudinal cohort studies are still needed to better analyze the influence of eosinophil levels on the clinical traits of AR.

Eco-friendly one-step egg white gel preparation for sensitive detection of 13 trichothecenes in oats using UHPLC-MS/MS.

Oat products have gained widespread recognition as a health food due to their rich and balanced nutritional profile and convenience. However, the unique matrix composition of oats, which differs significantly from other cereals, presents specific challenges for mycotoxin analysis. This study presents an ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method enhanced with an innovative egg white gel pretreatment for the simultaneous analysis of 13 regulated and unregulated trichothecenes in oats. The method demonstrated excellent performance with high accuracy (> 87.5%), repeatability (< 5.7%), and reproducibility (< 8.1%). Analysis of 100 commercial oat products revealed a concerning detection rate (78%) for at least one of the 11 trichothecenes investigated. Notably, deoxynivalenol, exceeding the standard limit in 2% of samples, exhibited the highest detection rate (62%). Additionally, concerning co-occurrence patterns and positive correlations were observed, highlighting potential synergistic effects. The first-time detection of unregulated mycotoxins (T-2 triol, 4,15-diacetoxyscirpenol, 15-acetoxyscirpenol, and neosolaniol) underscores the need for comprehensive monitoring. This method, while developed for oats, shows potential for broader application to other cereals, though further investigation and confirmation are necessary. These findings suggest a potentially underestimated risk of trichothecenes in oats, necessitating continuous monitoring to ensure consumer safety.

Low protein expression of LZTR1 in hepatocellular carcinoma triggers tumorigenesis via activating the RAS/RAF/MEK/ERK signaling.

LZTR1 is a substrate specific adaptor for E3 ligase involved in the ubiquitination and degradation of RAS GTPases, which inhibits the RAS/RAF/MEK/ERK signaling to suppress the pathogenesis of Noonan syndrome and glioblastoma. However, it's still unknown whether LZTR1 destabilizes RAS GTPases to suppress HCC progression by inhibiting these signaling pathway. Lenvatinib is the first-line drug for the treatment of advanced HCC, however, it has high drug resistance. To explore the roles of LZTR1 in HCC progression and the underlying mechanisms of lenvatinib resistance, techniques such as bioinformatics analysis, immunohistochemical staining, RT-qPCR, Western blot, cell functional experiments, small interfering RNA transfection and cycloheximide chase assay were applied in our study. Among these, bioinformatics analysis and immunohistochemical staining results indicated that LZTR1 protein was aberrantly expressed at low levels in HCC tissues, and low protein expression of LZTR1 was associated with poor prognosis of HCC patients. In vitro functional experiments confirmed that low expression of LZTR1 promoted HCC cell proliferation and migration via the aberrant activation of the RAS/RAF/MEK/ERK signaling due to the dysregulation of LZTR1-induced KRAS ubiquitination and degradation. Transwell assays revealed that blocking of LZTR1-mediated KRAS degradation could induce lenvatinib resistance in HCC cells. In conclusion, our study revealed that LZTR1 knockdown promoted HCC cell proliferation and migration, and induced lenvatinib resistance via activating the RAS/RAF/MEK/ERK signaling, which may provide new ideas for HCC treatment.

Crosstalk between epitranscriptomic and epigenomic modifications and its implication in human diseases.

Crosstalk between N6-methyladenosine (m6A) and epigenomes is crucial for gene regulation, but its regulatory directionality and disease significance remain unclear. Here, we utilize quantitative trait loci (QTLs) as genetic instruments to delineate directional maps of crosstalk between m6A and two epigenomic traits, DNA methylation (DNAme) and H3K27ac. We identify 47 m6A-to-H3K27ac and 4,733 m6A-to-DNAme and, in the reverse direction, 106 H3K27ac-to-m6A and 61,775 DNAme-to-m6A regulatory loci, with differential genomic location preference observed for different regulatory directions. Integrating these maps with complex diseases, we prioritize 20 genome-wide association study (GWAS) loci for neuroticism, depression, and narcolepsy in brain; 1,767 variants for asthma and expiratory flow traits in lung; and 249 for coronary artery disease, blood pressure, and pulse rate in muscle. This study establishes disease regulatory paths, such as rs3768410-DNAme-m6A-asthma and rs56104944-m6A-DNAme-hypertension, uncovering locus-specific crosstalk between m6A and epigenomic layers and offering insights into regulatory circuits underlying human diseases.

Integrative Analysis of Lactylome and Proteome of Hypertrophic Scar To Identify Pathways or Proteins Associated with Disease Development.

Lactylation (Kla), a recently discovered post-translational modification derived from lactate, plays crucial roles in various cellular processes. However, the specific influence of lactylation on the biological processes underlying hypertrophic scar formation remains unclear. In this study, we present a comprehensive profiling of the lactylome and proteome in both hypertrophic scars and adjacent normal skin tissues. A total of 1023 Kla sites originating from 338 nonhistone proteins were identified based on lactylome analysis. Proteome analysis in hypertrophic scar and adjacent skin samples revealed the identification of 2008 proteins. It is worth noting that Kla exhibits a preference for genes associated with ribosome function as well as glycolysis/gluconeogenesis in both normal skin and hypertrophic scar tissues. Furthermore, the functional enrichment analysis demonstrated that differentially lactyled proteins are primarily involved in proteoglycans, HIF-1, and AMPK signaling pathways. The combined analysis of the lactylome and proteome data highlighted a significant upregulation of 14 lactylation sites in hypertrophic scar tissues. Overall, our investigation unveiled the significant involvement of protein lactylation in the regulation of ribosome function as well as glycolysis/gluconeogenesis, potentially contributing to the formation of hypertrophic scars.

Comprehensive Identification and Characterization of HML-9 Group in Chimpanzee Genome.

Endogenous retroviruses (ERVs) are related to long terminal repeat (LTR) retrotransposons, comprising gene sequences of exogenous retroviruses integrated into the host genome and inherited according to Mendelian law. They are considered to have contributed greatly to the evolution of host genome structure and function. We previously characterized HERV-K HML-9 in the human genome. However, the biological function of this type of element in the genome of the chimpanzee, which is the closest living relative of humans, largely remains elusive. Therefore, the current study aims to characterize HML-9 in the chimpanzee genome and to compare the results with those in the human genome. Firstly, we report the distribution and genetic structural characterization of the 26 proviral elements and 38 solo LTR elements of HML-9 in the chimpanzee genome. The results showed that the distribution of these elements displayed a non-random integration pattern, and only six elements maintained a relatively complete structure. Then, we analyze their phylogeny and reveal that the identified elements all cluster together with HML-9 references and with those identified in the human genome. The HML-9 integration time was estimated based on the 2-LTR approach, and the results showed that HML-9 elements were integrated into the chimpanzee genome between 14 and 36 million years ago and into the human genome between 18 and 49 mya. In addition, conserved motifs, cis-regulatory regions, and enriched PBS sequence features in the chimpanzee genome were predicted based on bioinformatics. The results show that pathways significantly enriched for ERV LTR-regulated genes found in the chimpanzee genome are closely associated with disease development, including neurological and neurodevelopmental psychiatric disorders. In summary, the identification, characterization, and genomics of HML-9 presented here not only contribute to our understanding of the role of ERVs in primate evolution but also to our understanding of their biofunctional significance.

Lipidomic signatures in patients with early-onset and late-onset Preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific clinical syndrome and can be subdivided into early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) according to the gestational age of delivery. Patients with preeclampsia have aberrant lipid metabolism. This study aims to compare serum lipid profiles of normal pregnant women with EOPE or LOPE and screening potential biomarkers to diagnose EOPE or LOPE. METHODS: Twenty normal pregnant controls (NC), 19 EOPE, and 19 LOPE were recruited in this study. Untargeted lipidomics based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to compare their serum lipid profiles. RESULTS: The lipid metabolism profiles significantly differ among the NC, EOPE, and LOPE. Compared to the NC, there were 256 and 275 distinct lipids in the EOPE and LOPE, respectively. Furthermore, there were 42 different lipids between the LOPE and EOPE, of which eight were significantly associated with fetal birth weight and maternal urine protein. The five lipids that both differed in the EOPE and LOPE were DGTS (16:3/16:3), LPC (20:3), LPC (22:6), LPE (22:6), PC (18:5e/4:0), and a combination of them were a potential biomarker for predicting EOPE or LOPE. The receiver operating characteristic analysis revealed that the diagnostic power of the combination for distinguishing the EOPE from the NC and for distinguishing the LOPE from the NC can reach 1.000 and 0.992, respectively. The association between the lipid modules and clinical characteristics of EOPE and LOPE was investigated by the weighted gene co-expression network analysis (WGCNA). The results demonstrated that the main different metabolism pathway between the EOPE and LOPE was enriched in glycerophospholipid metabolism. CONCLUSIONS: Lipid metabolism disorders may be a potential mechanism of the pathogenesis of preeclampsia. Lipid metabolites have the potential to serve as biomarkers in patients with EOPE or LOPE. Furthermore, lipid metabolites correlate with clinical severity indicators for patients with EOPE and LOPE, including fetal birth weight and maternal urine protein levels.

Restricted-Access Media Column Switching Online Solid-Phase Extraction UHPLC-MS/MS for the Determination of Seven Type B Trichothecenes in Whole-Grain Preprocessed Foods and Human Exposure Risk Assessment.

With increasing health awareness and the accelerating pace of life, whole-grain prepared foods have gained popularity due to their health benefits and convenience. However, the potential risk of type B trichothecene toxins has also increased, and these mycotoxins in such foods are rarely regulated. In this study, a quantitative method combining a single-valve dual-column automatic online solid-phase extraction system with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for the first time using restricted-access media columns. This method can simultaneously determine trace residues of seven type B trichothecenes within 15 min. The method is convenient, sensitive (limit of detection and quantification of 0.05-0.6 µg/kg and 0.15-2 µg/kg, respectively), accurate (recovery rates of 90.3%-106.6%, relative standard deviation < 4.3%), and robust (>1000 times). The established method was applied to 160 prepared food samples of eight categories sold in China. At least one toxin was detected in 70% of the samples. Whole-wheat dumpling wrappers had the highest contamination rate (95%) and the highest total content of type B trichothecenes in a single sample (2077.3 µg/kg). Exposure risk assessment indicated that the contamination of whole-grain prepared foods has been underestimated. The total health risk index of whole-wheat dumpling wrappers, which are susceptible to deoxynivalenol, reached 136.41%, posing a significant threat to human health. Effective measures urgently need to be taken to control this risk.

A unified classification system for HIV-1 5' long terminal repeats.

The HIV-1 provirus mainly consists of internal coding region flanked by 1 long terminal repeats (LTRs) at each terminus. The LTRs play important roles in HIV-1 reverse transcription, integration, and transcription. However, despite of the significant study advances of the internal coding regions of HIV-1 by using definite reference classification, there are no systematic and phylogenetic classifications for HIV-1 5' LTRs, which hinders our elaboration on 5' LTR and a better understanding of the viral origin, spread and therapy. Here, by analyzing all available resources of 5' LTR sequences in public databases following 4 recognized principles for the reference classification, 83 representatives and 14 consensus sequences were identified as representatives of 2 groups, 6 subtypes, 6 sub-subtypes, and 9 CRFs. To test the reliability of the supplemented classification system, the constructed references were applied to identify the 5' LTR assignment of the 22 clinical isolates in China. The results revealed that 16 out of 22 tested strains showed a consistent subtype classification with the previous LTR-independent classification system. However, 6 strains, for which recombination events within 5' LTR were demonstrated, unexpectedly showed a different subtype classification, leading a significant change of binding sites for important transcription factors including SP1, p53, and NF-κB. The binding change of these transcriptional factors would probably affect the transcriptional activity of 5' LTR. This study supplemented a unified classification system for HIV-1 5' LTRs, which will facilitate HIV-1 characterization and be helpful for both basic and clinical research fields.

Comparison of clinical traits for seasonal and perennial allergic rhinitis during allergen exposure.

Background: Allergic rhinitis (AR) is traditionally subdivided into seasonal AR (SAR) and perennial AR (PAR) according to the type of allergen and the occurrence of symptoms during the year. There are currently no reports on the comparison of trait profiles for SAR and PAR during the allergen exposure. Purpose: The purpose of this study was to analyze the clinical characteristics of SAR and PAR during respective allergen exposure periods to provide valuable information for the development of treatment strategies. Methods: This study was performed between August 1, 2021, and January 31, 2022, in the Department of Allergy, Beijing Tongren Hospital. We continuously included diagnosed SAR and PAR outpatients who volunteered to participate in the survey. A questionnaire with regard to medical history, severity of symptoms, and diagnosis and treatment status was collected. Results: A total of 296 patients with SAR and 448 with PAR were finally recruited. Patients with SAR had more severe rhinorrhea compared with patients with PAR (p < 0.001), whereas there was no statistically significant difference in the severity of itching, sneezing, and congestion between the two entities (p ≥ 0.05). Both the gritty and watery eyes of patients with SAR were noticeably more severe than those of patients with PAR (PTotal Ocular Symptom Score [PTOSS] < 0.001). AR symptom severity is mainly associated with the comorbid allergic conjunctivitis (odds ratio 1.94 [95% confidence interval, 1.21-3.09]). SAR patients and PAR patients show no statistically significant differences in terms of their frequency of visits, annual expenditure, and choice of medication treatment for AR (p > 0.05). The overall control under standard medication of both patients with PAR and those with SAR is not ideal, especially in SAR. Conclusion: The current cross-sectional study demonstrated that the patients with SAR exhibited more severe overall clinical symptoms than those with PAR, especially nasal rhinorrhea and gritty and watery eyes. Both of the two disease entities have poor control under standardized medication treatment, especially in SAR. Further multicenter longitudinal studies that involve larger and more diverse populations should be conducted to provide a more accurate and comprehensive understanding of the condition.

Enterovirus 71 Activates Plasmacytoid Dendritic Cell-Dependent PSGL-1 Binding Independent of Productive Infection.

Enterovirus 71 (EV71) is a significant causative agent of hand, foot, and mouth disease, with potential serious neurologic complications or fatal outcomes. The lack of effective treatments for EV71 infection is attributed to its elusive pathogenicity. Our study reveals that human plasmacytoid dendritic cells (pDCs), the main type I IFN-producing cells, selectively express scavenger receptor class B, member 2 (SCARB2) and P-selectin glycoprotein ligand 1 (PSGL-1), crucial cellular receptors for EV71. Some strains of EV71 can replicate within pDCs and stimulate IFN-α production. The activation of pDCs by EV71 is hindered by Abs to PSGL-1 and soluble PSGL-1, whereas Abs to SCARB2 and soluble SCARB2 have a less pronounced effect. Our data suggest that only strains binding to PSGL-1, more commonly found in severe cases, can replicate in pDCs and induce IFN-α secretion, highlighting the importance of PSGL-1 in these processes. Furthermore, IFN-α secretion by pDCs can be triggered by EV71 or UV-inactivated EV71 virions, indicating that productive infection is not necessary for pDC activation. These findings provide new insights into the interaction between EV71 and pDCs, suggesting that pDC activation could potentially mitigate the severity of EV71-related diseases.

Metabolic engineering of Candida tropicalis for efficient 1,2,4-butanetriol production.

1,2,4-Butanetriol serves as a precursor in the manufacture of diverse pharmaceuticals and the energetic plasticizer 1,2,4-butanetriol trinitrate. The study involved further modifications to an engineered Candida tropicalis strain, aimed at improving the production efficiency of 1,2,4-butanetriol. Faced with the issue of xylonate accumulation due to the low activity of heterologous xylonate dehydratase, we modulated iron metabolism at the transcriptional level to boost intracellular iron ion availability, thus enhancing the enzyme activity by 2.2-fold. Addressing the NADPH shortfall encountered during 1,2,4-butanetriol biosynthesis, we overexpressed pivotal genes in the NADPH regeneration pathway, achieving a 1,2,4-butanetriol yield of 3.2 g/L. The introduction of calcium carbonate to maintain pH balance led to an increased yield of 4 g/L, marking a 111% improvement over the baseline strain. Finally, the use of corncob hydrolysate as a substrate culminated in 1,2,4-butanetriol production of 3.42 g/L, thereby identifying a novel host for the conversion of corncob hydrolysate to 1,2,4-butanetriol.

Near Full-Length Genome Characterization of Two Novel Unique Recombinants (CRF01_AE/CRF07_BC) in Beijing, China.

With the prevalence of human immunodeficiency virus type 1 (HIV-1) CRF01_AE and CRF07_BC subtypes in China, the co-circulation of multiple subtypes in the HIV-1-positive population may result in dual infection or superinfection in the population, leading to the emergence of unique recombinant forms (URFs) of the HIV-1 virus. In this study, two second-generation unique recombinant strains, BI0114 and BI0116, were identified, and their near full-length genome sequences were obtained. Recombination analysis showed that both sequences were isoforms of URF_0107, and they were second-generation unique recombinant strains formed by the recombination of CRF01_AE and CRF07_BC, with the isoforms being CRF01_AE and CRF0107_BC, respectively. The continued emergence of novel CRF01_AE/CRF07_BC recombinant strains suggests that the epidemiological, preventive, and control situation of HIV-1 is complex and that the relevant health authorities urgently need to establish responses to the challenges posed by changes in the pattern of strain recombination.

Near-full-length genome analysis of two novel HIV second recombinant forms in Hebei, China.

The number of individuals infected with HIV-1 among men who have sex with men (MSM) has risen rapidly in recent years in China, and the subtypes CRF01_AE, CRF07_BC, and B, as well as many novel unique recombinant forms (URFs) are prevalent among them. Co-circulation of strains among MSM populations allows the generation of circulating recombinant forms (CRFs) and URFs. In this study, we identified two new URFs from two HIV-1-positive subjects who were infected through homosexual contact in Hebei, China. Analysis of near-full-length genome sequences, using phylogenetic and recombination analysis showed that the two URFs originated from CRF01_AE, CRF07_BC, and B, and CRF01_AE segments in the backbone of the URFs were derived from cluster 4 of CRF01_AE. The CRF07_BC segments of two URFs were clustered with 07BC_N in a phylogenetic tree. The identification of novel URFs with complex genomic structures shows that it is necessary to strengthen surveillance of HIV-1 variants in MSM populations in this region.

Comprehensive characterization of ERV-K (HML-8) in the chimpanzee genome revealed less genomic activity than humans.

Endogenous retroviruses (ERVs) originate from ancestral germline infections caused by exogenous retroviruses. Throughout evolution, they have become fixed within the genome of the animals into which they were integrated. As ERV elements coevolve with the host, they are normally epigenetically silenced and can become upregulated in a series of physiological and pathological processes. Generally, a detailed ERV profile in the host genome is critical for understanding the evolutionary history and functional performance of the host genome. We previously characterized and cataloged all the ERV-K subtype HML-8 loci in the human genome; however, this has not been done for the chimpanzee, the nearest living relative of humans. In this study, we aimed to catalog and characterize the integration of HML-8 in the chimpanzee genome and compare it with the integration of HML-8 in the human genome. We analyzed the integration of HML-8 and found that HML-8 pervasively invaded the chimpanzee genome. A total of 76 proviral elements were characterized on 23/24 chromosomes, including detailed elements distribution, structure, phylogeny, integration time, and their potential to regulate adjacent genes. The incomplete structure of HML-8 proviral LTRs will undoubtedly affect their activity. Moreover, the results indicated that HML-8 integration occurred before the divergence between humans and chimpanzees. Furthermore, chimpanzees include more HML-8 proviral elements (76 vs. 40) and fewer solo long terminal repeats (LTR) (0 vs. 5) than humans. These results suggested that chimpanzee genome activity is less than the human genome and that humans may have a better ability to shape and screen integrated proviral elements. Our work is informative in both an evolutionary and a functional context for ERVs.

Lung Ultrasound Assessment of Lung Hyperinflation in Patients with Stable COPD: An Effective Diagnostic Tool.

Purpose: To evaluate the degree of lung hyperinflation (LH) in patients with stable chronic obstructive pulmonary disease (COPD) by lung ultrasound score (LUS) and assess its value. Patients and Methods: We conducted a study of 149 patients with stable COPD and 100 healthy controls recruited by the Second Affiliated Hospital of Fujian Medical University. The pleural sliding displacement (PSD) was measured, the sliding of the pleura in different areas was observed, and LUS was calculated from both of them. The diaphragm excursion (DE), residual capacity (RV), total lung capacity (TLC), inspiratory capacity (IC) and functional residual capacity (FRC) were measured. We described the correlation between ultrasound indicators and pulmonary function indicators reflecting LH. Multiple linear regression analysis was used. The ROC curves of LUS and DE were drawn to evaluate their diagnostic efficacy, and De Long method was used for comparison. Results: (1) The LUS of patients with stable COPD were positively correlated with RV, TLC, RV/TLC and FRC and negatively correlated with IC and IC/TLC (r1=0.72, r2=0.41, r3=0.72, r4=0.70, r5=-0.56, r6=-0.65, P < 0.001). The correlation was stronger than that between DE at maximal deep inspiration and the corresponding pulmonary function indices (r1=-0.41, r2=-0.26, r3=-0.40, r4=-0.43, r5=0.30, r6=0.37, P < 0.001). (2) Multiple linear regression analysis showed that LUS were significantly correlated with IC/TLC and RV/TLC. (3) With IC/TLC<25% and RV/TLC>60% as the diagnostic criterion of severe LH, the areas under the ROC curves of LUS and DE at maximal deep inspiration for diagnosing severe LH were 0.914 and 0.385, 0.845 and 0.543, respectively (P < 0.001). Conclusion: The lung ultrasound score is an important parameter for evaluating LH. LUS is better than DE at maximal deep inspiration for diagnosing severe LH and is expected to become an effective auxiliary tool for evaluating LH.