Neferine mitigates angiotensin II-induced atrial fibrillation and fibrosis via upregulation of Nrf2/HO-1 and inhibition of TGF-ß/p-Smad2/3 pathways.

BACKGROUND: Atrial fibrillation (AF) is often associated with atrial fibrosis and oxidative stress. Neferine, a bisbenzylisoquinoline alkaloid, has been reported to exert an antiarrhythmic effect. However, its impact on Angiotensin II (Ang II) infusion-induced AF and the underlying mechanism remains unclear. This study aimed to investigate whether neferine alleviates Ang II-induced AF and explore the underlying mechanisms. METHODS: Mice subjected to Ang II infusion to induce AF were concurrently treated with neferine or saline. AF incidence, myocardial cell size, fibrosis, and oxidative stress were then examined. RESULTS: Neferine treatment inhibited Ang II-induced AF, atrial size augmentation, and atrial fibrosis. Additionally, we observed that Ang II increased reactive oxygen species (ROS) generation, induced mitochondrial membrane potential depolarization, and reduced glutathione (GSH) and superoxide dismutase (SOD) levels, which were reversed to some extent by neferine. Mechanistically, neferine activated the Nrf2/HO-1 signaling pathway and inhibited TGF-ß/p-Smad2/3 in Ang II-infused atria. Zinc Protoporphyrin (ZnPP), an HO-1 inhibitor, reduced the anti-oxidative effect of neferine to some extent and subsequently abolished the beneficial effect of neferine on Ang II-induced AF. CONCLUSIONS: These findings provide hitherto undocumented evidence that the protective role of neferine in Ang II-induced AF is dependent on HO-1.

Chronic kidney disease: a contraindication for using biodegradable magnesium or its alloys as potential orthopedic implants?

Magnesium (Mg) has gained widespread recognition as a potential revolutionary orthopedic biomaterial. However, whether the biodegradation of the Mg-based orthopedic implants would pose a risk to patients with chronic kidney disease (CKD) remains undetermined as the kidney is a key organ regulating mineral homeostasis. A rat CKD model was established by a 5/6 subtotal nephrectomy approach, followed by intramedullary implantation of three types of pins: stainless steel, high pure Mg with high corrosion resistance, and the Mg-Sr-Zn alloy with a fast degradation rate. The long-term biosafety of the biodegradable Mg or its alloys as orthopedic implants were systematically evaluated. During an experimental period of 12 weeks, the implantation did not result in a substantial rise of Mg ion concentration in serum or major organs such as hearts, livers, spleens, lungs, or kidneys. No pathological changes were observed in organs using various histological techniques. No significantly increased iNOS-positive cells or apoptotic cells in these organs were identified. The biodegradable Mg or its alloys as orthopedic implants did not pose an extra health risk to CKD rats at long-term follow-up, suggesting that these biodegradable orthopedic devices might be suitable for most target populations, including patients with CKD.

Mediating effect of the NLR on the relationship between HbA1c and left atrial stiffness in overweight patients with hypertension.

BACKGROUND: We aimed to investigate the association between hemoglobin A1c (HbA1c) and left atrial (LA) stiffness in patients with hypertension and to explore the mediating effect of the neutrophil/lymphocyte ratio (NLR) on this association. METHODS: Essential hypertensive patients (n=292) aged 18 to 83 years were enrolled and divided into two groups based on the LA stiffness index (LASI): Group I (LASI≤0.32, n=146) and Group II (LASI>0.32, n=146). The LASI was defined as the ratio of early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') to LA reservoir strain. Multivariate linear regression analysis was performed to determine the independent predictors of the LASI. RESULTS: Age, BMI, SBP, HbA1c, CRP and the NLR were significantly greater in Group II than in Group I (P<0.05). Additionally, Group II had a greater LA volume index (LAVI), left ventricular mass index (LVMI), and E/e' and lower LA reservoir, conduit and booster pump strains than Group I (P<0.001). Univariate and multivariate linear regression models revealed that age, SBP, HbA1c, and the NLR were independently associated with the LASI. Further mediation analysis was performed to determine the mediating effect of the NLR on the association between HbA1c and the LASI and revealed that the NLR had a mediating role only in overweight hypertensive patients, and the proportion of the mediating effect was 21.9%. CONCLUSIONS: The NLR was independently correlated with the LASI and played a mediating role in the relationship between HbA1c and the LASI in overweight hypertensive patients.

The role of dermal fibroblasts in autoimmune skin diseases.

Fibroblasts are an important subset of mesenchymal cells in maintaining skin homeostasis and resisting harmful stimuli. Meanwhile, fibroblasts modulate immune cell function by secreting cytokines, thereby implicating their involvement in various dermatological conditions such as psoriasis, vitiligo, and atopic dermatitis. Recently, variations in the subtypes of fibroblasts and their expression profiles have been identified in these prevalent autoimmune skin diseases, implying that fibroblasts may exhibit distinct functionalities across different diseases. In this review, from the perspective of their fundamental functions and remarkable heterogeneity, we have comprehensively collected evidence on the role of fibroblasts and their distinct subpopulations in psoriasis, vitiligo, atopic dermatitis, and scleroderma. Importantly, these findings hold promise for guiding future research directions and identifying novel therapeutic targets for treating these diseases.

Exosomes containing miR-1469 regulate natural killer cells by targeting CD122 in non-segmental vitiligo.

BACKGROUND: Plasma exosomal microRNAs (miRNAs) have been used as potential biomarkers for various diseases and have been investigated for their possible involvement in the pathogenesis of vitiligo. However, the miRNA expression profile of plasma exosomes in patients with non-segmental vitiligo (NSV) has not been determined yet. OBJECTIVE: To screen differentially expressed microRNAs in plasma exosomes derived from patients with NSV and explore their roles in the pathogenesis of NSV. METHODS: High-throughput sequencing was performed to determine the expression profiles of exosomal miRNAs in NSV. The effect of upregulated miR-1469 in NSV circulating exosomes on natural killer (NK) cells was further investigated using various molecular biological techniques. RESULTS: MiR-1469 was identified as a candidate biomarker whose expression was significantly increased in circulating exosomes of NSV patients. Circulating exosomes were internalized by NK cells and increased NK cell proliferation viability and IFN-γ secretion capacity delivering miR-1469. Further studies revealed that the upregulation of CD122, the predicted target of miR-1469, could partially reverse the effect of miR-1469 on natural killer cells. CONCLUSION: Alterations in plasma exosomal cargo occur in NSV and appear to contribute to NK cell dysfunction. Exosomal miR-1469 may be a biomarker of disease activity and could be used as a therapeutic drug target against innate immunity in NSV patients. The present study provides new insights into the role of exosomal miRNAs in NSV and suggests a novel miR-1469-CD122-IFN-γ pathway of NK cell underlying pathogenesis of NSV.

Bacteria and viruses and clinical outcomes of asthma-bronchiectasis overlap syndrome: A cohort study.

BACKGROUND: Despite the high prevalence of co-existing bronchiectasis and asthma (asthma-bronchiectasis overlap syndrome [ABOS]), little is known regarding the dominant pathogens and clinical correlates. OBJECTIVE: To investigate the bacteria and viruses which differentially dominate in ABOS (including its subtypes) compared with bronchiectasis alone, and determine their relevance with bronchiectasis severity and exacerbations. METHODS: This was a prospective observational cohort study conducted between March 2017 and August 2023. We included 81 patients with ABOS and 107 patients with bronchiectasis alone. At steady-state baseline, patients underwent comprehensive assessments and sputum collection for bacterial culture and viral detection (quantitative polymerase-chain-reaction). Patients were followed-up to record exacerbation and spirometry. RESULTS: Patients with ABOS had significantly higher symptom burden and exacerbation frequency than those with bronchiectasis alone. Despite similar pathogen spectrum, the rate of bacteria-virus co-detection increased less substantially at acute exacerbations (AE) onset than at steady-state compared with bronchiectasis alone. Pathogenic bacteria (particularly Pseudomonas aeruginosa) were detected fairly common (exceeding 50%) in ABOS and were associated with greater severity of bronchiectasis when stable and conferred greater exacerbation risks at follow-up. Viral but not bacterial compositions changed substantially at AE onset compared with clinical stability. Higher blood eosinophil count, moderate-to-severe bronchiectasis and non-atopy were associated with higher odds of bacterial, but not viral, detection (all p < 0.05). CONCLUSION: Detection of bacteria or virus is associated with bronchiectasis severity or clinical outcomes in ABOS. This highlights the importance of integrating sputum microbial assessment for ascertaining the dominant pathophysiology (atopy vs. infection) and longitudinal trajectory prediction in ABOS.

Exosomal miRNAs in autoimmune skin diseases.

Exosomes, bilaterally phospholipid-coated small vesicles, are produced and released by nearly all cells, which comprise diverse biological macromolecules, including proteins, DNA, RNA, and others, that participate in the regulation of their biological functions. An increasing number of studies have revealed that the contents of exosomes, particularly microRNA(miRNA), play a significant role in the pathogenesis of various diseases, including autoimmune skin diseases. MiRNA is a class of single-stranded non-coding RNA molecules that possess approximately 22 nucleotides in length with the capability of binding to the untranslated as well as coding regions of target mRNA to regulate gene expression precisely at the post-transcriptional level. Various exosomal miRNAs have been found to be significantly expressed in some autoimmune skin diseases and involved in the pathogenesis of conditions via regulating the secretion of crucial pathogenic cytokines and the direction of immune cell differentiation. Thus, exosomal miRNAs might be promising biomarkers for monitoring disease progression, relapse and reflection to treatment based on their functions and changes. This review summarized the current studies on exosomal miRNAs in several common autoimmune skin diseases, aiming to dissect the underlying mechanism from a new perspective, seek novel biomarkers for disease monitoring and lay the foundation for developing innovative target therapy in the future.

1,25-Dihydroxyvitamin D3 Provides Benefits in Vitiligo Based on Modulation of CD8+ T Cell Glycolysis and Function.

Vitiligo is a common autoimmune skin disease caused by autoreactive CD8+ T cells. The diverse effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on immune cell metabolism and proliferation have made it an interesting candidate as a supporting therapeutic option in various autoimmune diseases. This study aimed to elucidate the immunomodulatory effects of 1,25(OH)2D3 in vitiligo. Cross-sectional relationships between serum 1,25(OH)2D3 levels and disease characteristics were investigated in 327 patients with vitiligo. The immunomodulatory and therapeutic effects of 1,25(OH)2D3 were then investigated in vivo and in vitro, respectively. We found that 1,25(OH)2D3 deficiency was associated with hyperactivity of CD8+ T cells in the vitiligo cohort. In addition, 1,25(OH)2D3 suppressed glycolysis by activating the AMP-activated protein kinase (AMPK) signaling pathway, thereby inhibiting the proliferation, cytotoxicity and aberrant activation of CD8+ T cells. Finally, the in vivo administration of 1,25(OH)2D3 to melanocyte-associated vitiligo (MAV) mice reduced the infiltration and function of CD8+ T cells and promoted repigmentation. In conclusion, 1,25(OH)2D3 may serve as an essential biomarker of the progression and severity of vitiligo. The modulation of autoreactive CD8+ T cell function and glycolysis by 1,25(OH)2D3 may be a novel approach for treating vitiligo.

Vishniacozyma pseudocarnescens sp. nov., a new anamorphic tremellomycetous yeast species.

Three strains belonging to the basidiomycetous yeast genus Vishniacozyma were isolated from marine water samples collected from intertidal zones in Liaoning province, northeast China. Phylogenetic analyses based on the sequences of the small subunit (SSU) ribosomal DNA (rDNA), the D1/D2 domain of the large subunit (LSU) ribosomal DNA (rDNA), the internal transcribed spacer region (ITS), the two subunits of DNA polymerase II (RPB1 and RPB2), the translation elongation factor 1-α (TEF1), and the mitochondrial gene cytochrome b (CYTB) showed that these strains together with 20 strains from various geographic and ecological origins from other regions of the world represent a novel species in the genus Vishniacozyma. We propose the name Vishniacozyma pseudocarnescens sp. nov. (holotype CGMCC 2.6457) for the new species, which differs phenotypically from its close relatives V. carnescens, V. tephrensis, and V. victoriae by its ability to grow at 30 °C and on 50 % (w/v) glucose-yeast extract agar.

Moderating effect of mindfulness on the relationship between anxiety and somatization symptoms in middle-aged and elderly female patients with hypertension.

To explore the moderating effect of mindfulness on the relationship between anxiety and somatization symptoms in middle-aged and elderly female patients with hypertension and provide a foundation for the development of more effective mindfulness intervention strategies. A total of 109 middle-aged and elderly female patients with hypertension participated in this cross-sectional study from April to July 2022 and provided valid responses to the Five Facet Mindfulness Questionnaire (FFMQ), the Hospital Anxiety and Depression Scale (HADS), and the Somatization Symptom Self-rating Scale (SSS). The moderating effect of mindfulness was determined using multiple linear regression. The participants' average scores were as follows: mindfulness: 123.86 ± 10.49; anxiety: 7.41 ± 3.62; and somatization symptoms: 41.2 ± 9.44. The anxiety (P = .000) and somatization symptoms (P = .001) of participants with high mindfulness were significantly reduced. Anxiety was positively correlated with somatization symptoms (r = 0.606, P = .000), while mindfulness was negatively correlated with both anxiety (r = -0.468, P = .000) and somatization symptoms (r = -0.439, P = .000). Moreover, mindfulness had a significant moderating effect on the relationship between anxiety and somatization symptoms (n = 109) (B = -0.166, t = -2.125, P = .036). The effect of mindfulness on anxiety and somatization symptoms was more significant in participants with low mindfulness levels (n = 56) (B = 0.144, t = 2.805, P = .008) than in participants with high mindfulness levels (n = 53) (B = -0.037, t = -0.864, P = .393). The moderating effect analysis based on regression analysis showed that mindfulness had a significant moderating effect on anxiety and somatization symptoms, especially in participants with low mindfulness levels.

Sputum pathogen spectrum and clinical outcomes of upper respiratory tract infection in bronchiectasis exacerbation: a prospective cohort study.

Upper respiratory tract infection (URTI) is common in humans. We sought to profile sputum pathogen spectrum and impact of URTI on acute exacerbation of bronchiectasis (AE). Between March 2017 and December 2021, we prospectively collected sputum from adults with bronchiectasis. We stratified AEs into events related (URTI-AE) and unrelated to URTI (non-URTI-AE). We captured URTI without onset of AE (URTI-non-AE). We did bacterial culture and viral detection with polymerase chain reaction, and explored the pathogen spectrum and clinical impacts of URTI-AE via longitudinal follow-up. Finally, we collected 479 non-AE samples (113 collected at URTI-non-AE and 225 collected at clinically stable) and 170 AE samples (89 collected at URTI-AE and 81 collect at non-URTI-AE). The viral detection rate was significantly higher in URTI-AE (46.1%) than in non-URTI-AE (4.9%) and URTI-non-AE (11.5%) (both P < 0.01). Rhinovirus [odds ratio (OR): 5.00, 95% confidence interval (95%CI): 1.06-23.56, P = 0.03] detection was independently associated with URTI-AE compared with non-URTI-AE. URTI-AE tended to yield higher viral load and detection rate of rhinovirus, metapneumovirus and bacterial shifting compared with URTI-non-AE. URTI-AE was associated with higher initial viral loads (esp. rhinovirus, metapneumovirus), greater symptom burden (higher scores of three validated questionnaires) and prolonged recovery compared to those without. Having experienced URTI-AE predicted a greater risk of future URTI-AE (OR: 10.90, 95%CI: 3.60-33.05). In summary, URTI is associated with a distinct pathogen spectrum and aggravates bronchiectasis exacerbation, providing the scientific rationale for the prevention of URTI to hinder bronchiectasis progression.

Construction of a non-negative matrix factorization model of immunogenic cell death-related genes in lung adenocarcinoma and analysis of survival prognosis.

Purpose: To explore the effectiveness of the model based on non-negative matrix factorization (NMF), analyze the tumor microenvironment and immune microenvironment for evaluating the prognosis of lung adenocarcinoma, establish a risk model, and screen independent prognostic factors. Methods: Downloading the transcription data files and clinical information files of lung adenocarcinoma from TCGA database and GO database, the R software was used to establish the NMF cluster model, and then the survival analysis between groups, tumor microenvironment analysis, and immune microenvironment analysis was performed according to the NMF cluster result. R software was used to construct prognostic models and calculate risk scores. Survival analysis was used to compare survival differences between different risk score groups. Results: Two ICD subgroups were established according to the NMF model. The survival of the ICD low-expression subgroup was better than that of the ICD high-expression subgroup. Univariate COX analysis screened out HSP90AA1, IL1, and NT5E as prognostic genes, and the prognostic model established on this basis has clinical guiding significance. Conclusion: The model based on NMF has the prognostic ability for lung adenocarcinoma, and the prognostic model of ICD-related genes has a certain guiding significance for survival.

Motile Ciliary Disorders of the Nasal Epithelium in Adults With Bronchiectasis.

BACKGROUND: Motile ciliary disorder (MCD) has been implicated in chronic inflammatory airway diseases such as asthma and COPD. RESEARCH QUESTION: What are the characteristics of MCD of the nasal epithelium and its association with disease severity and inflammatory endotypes in adults with bronchiectasis? STUDY DESIGN AND METHODS: In this observational study, we recruited 167 patients with bronchiectasis and 39 healthy control participants who underwent brushing of the nasal epithelium. A subgroup of patients underwent bronchoscopy for bronchial epithelium sampling (n = 13), elective surgery for bronchial epithelium biopsy (n = 18), and blood sampling for next-generation sequencing (n = 37). We characterized systemic and airway inflammatory endotypes in bronchiectasis. We conducted immunofluorescence assays to profile ultrastructural (dynein axonemal heavy chain 5 [DNAH5], dynein intermediate chain 1 [DNAI1], radial spoke head protein 9 [RSPH9]) and ciliogenesis marker expression (Ezrin). RESULTS: MCD was present in 89.8% of patients with bronchiectasis, 67.6% showed secondary MCD, and 16.2% showed primary plus secondary MCD. Compared with healthy control participants, patients with bronchiectasis yielded abnormal staining patterns of DNAH5, DNAI1, and RSPH9 (but not Ezrin) that were more prominent in moderate to severe bronchiectasis. MCD pattern scores largely were consistent between upper and lower airways and between large-to-medium and small airways in bronchiectasis. Coexisting nasal diseases and asthma did not confound nasal ciliary ultrastructural marker expression significantly. The propensity of MCD was unaffected by the airway or systemic inflammatory endotypes. MCD, particularly an ultrastructural abnormality, was notable in patients with mild bronchiectasis who showed blood or sputum eosinophilia. INTERPRETATION: Nasal ciliary markers profiling provides complimentary information to clinical endotyping of bronchiectasis.

Integrative genomic and transcriptomic profiling reveals distinct molecular subsets in adult mixed phenotype acute leukemia.

Mixed phenotype acute leukemia (MPAL) is a subtype of leukemia in which lymphoid and myeloid markers are co-expressed. Knowledge regarding the genetic features of MPAL is lacking due to its rarity and heterogeneity. Here, we applied an integrated genomic and transcriptomic approach to explore the molecular characteristics of 176 adult patients with MPAL, including 86 patients with T-lymphoid/myeloid MPAL (T/My MPAL-NOS), 42 with Ph+ MPAL, 36 with B-lymphoid/myeloid MPAL (B/My MPAL-NOS), 4 with t(v;11q23), and 8 with MPAL, NOS, rare types. Genetically, T/My MPAL-NOS was similar to B/T MPAL-NOS but differed from Ph+ MPAL and B/My MPAL-NOS. T/My MPAL-NOS exhibited higher CEBPA, DNMT3A, and NOTCH1 mutations. Ph+ MPAL demonstrated higher RUNX1 mutations. B/T MPAL-NOS showed higher NOTCH1 mutations. By integrating next-generation sequencing and RNA sequencing data of 89 MPAL patients, we defined eight molecular subgroups (G1-G8) with distinct mutational and gene expression characteristics. G1 was associated with CEBPA mutations, G2 and G3 with NOTCH1 mutations, G4 with BCL11B rearrangement and FLT3 mutations, G5 and G8 with BCR::ABL1 fusion, G6 with KMT2A rearrangement/KMT2A rearrangement-like features, and G7 with ZNF384 rearrangement/ZNF384 rearrangement-like characteristics. Subsequently, we analyzed single-cell RNA sequencing data from five patients. Groups G1, G2, G3, and G4 exhibited overexpression of hematopoietic stem cell disease-like and common myeloid progenitor disease-like signatures, G5 and G6 had high expression of granulocyte-monocyte progenitor disease-like and monocyte disease-like signatures, and G7 and G8 had common lymphoid progenitor disease-like signatures. Collectively, our findings indicate that integrative genomic and transcriptomic profiling may facilitate more precise diagnosis and develop better treatment options for MPAL.

Yeast Diversity in the Qaidam Basin Desert in China with the Description of Five New Yeast Species.

The Qaidam Basin is the highest and one of the largest and driest deserts on Earth. It is considered a mars analog area in China. In contrast to numerous studies concerning its geology, geophysical, and chemistry, relatively few studies have reported microbial diversity and distribution in this area. Here, we investigated culturable yeast diversity in the northeast Qaidam Basin. A total of 194 yeast strains were isolated, and 12 genera and 21 species were identified, among which 19 were basidiomycetous yeasts. Naganishia albida, N. adeliensis, and Filobasidium magnum were the three most dominant species and were distributed in thirteen samples from eight locations. Five new species (Filobasidium chaidanensis, Kondoa globosum, Symmetrospora salmoneus, Teunia nitrariae, and Vishniacozyma pseudodimennae) were found and described based on ITS and D1D2 gene loci together with phenotypic characteristics and physiochemical analysis. Representative strains from each species were chosen for the salt-tolerant test, in which species showed different responses to different levels of NaCl concentrations. Further, the strain from soil can adapt well to the higher salt stress compared to those from plants or lichens. Our study represents the first report of the yeast diversity in the Qaidam Basin, including five new species, and also provides further information on the halotolerance of yeasts from the saline environment in mars analog.

Standardizing the classification of gastric cancer patients with limited and adequate number of retrieved lymph nodes: an externally validated approach using real-world data.

BACKGROUND: Currently, there is no formal consensus regarding a standard classification for gastric cancer (GC) patients with < 16 retrieved lymph nodes (rLNs). Here, this study aimed to validate a practical lymph node (LN) staging strategy to homogenize the nodal classification of GC cohorts comprising of both < 16 (Limited set) and ≥ 16 (Adequate set) rLNs. METHODS: All patients in this study underwent R0 gastrectomy. The overall survival (OS) difference between the Limited and Adequate set from a large Chinese multicenter dataset was analyzed. Using the 8th American Joint Committee on Cancer (AJCC) pathological nodal classification (pN) for GC as base, a modified nodal classification (N') resembling similar analogy as the 8th AJCC pN classification was developed. The performance of the proposed and 8th AJCC GC subgroups was compared and validated using the Surveillance, Epidemiology, and End Results (SEER) dataset comprising of 10,208 multi-ethnic GC cases. RESULTS: Significant difference in OS between the Limited and Adequate set (corresponding N0-N3a) using the 8th AJCC system was observed but the OS of N0limited vs. N1adequate, N1limited vs. N2adequate, N2limited vs. N3aadequate, and N3alimited vs. N3badequate subgroups was almost similar in the Chinese dataset. Therefore, we formulated an N' classification whereby only the nodal subgroups of the Limited set, except for pT1N0M0 cases as they underwent less extensive surgeries (D1 or D1 + gastrectomy), were re-classified to one higher nodal subgroup, while those of the Adequate set remained unchanged (N'0 = N0adequate + pT1N0M0limited, N'1 = N1adequate + N0limited (excluding pT1N0M0limited), N'2 = N2adequate + N1limited, N'3a = N3aadequate + N2limited, and N'3b = N3badequate + N3alimited). This N' classification demonstrated less heterogeneity in OS between the Limited and Adequate subgroups. Further analyses demonstrated superior statistical performance of the pTN'M system over the 8th AJCC edition and was successfully validated using the SEER dataset. CONCLUSION: The proposed nodal staging strategy was successfully validated in large multi-ethnic GC datasets and represents a practical approach for homogenizing the classification of GC cohorts comprising of patients with < 16 and ≥ 16 rLNs.

Highly diverged lineages of Saccharomyces paradoxus in temperate to subtropical climate zones in China.

The wild yeast Saccharomyces paradoxus has become a new model in ecology and evolutionary biology. Different lineages of S. paradoxus have been recognized across the world, but the distribution and genetic diversity of the species remain unknown in China, where the origin of its sibling species S. cerevisiae lies. In this study, we investigated the ecological and geographic distribution of S. paradoxus through an extensive field survey in China and performed population genomic analysis on a set of S. paradoxus strains, including 27 strains, representing different geographic and ecological origins within China, and 59 strains representing all the known lineages of the species recognized in the other regions of the world so far. We found two distinct lineages of S. paradoxus in China. The majority of the Chinese strains studied belong to the Far East lineage, and six strains belong to a novel highly diverged lineage. The distribution of these two lineages overlaps ecologically and geographically in temperate to subtropical climate zones in China. With the addition of the new China lineage, the Eurasian population of S. paradoxus exhibits higher genetic diversity than the American population. We observed more possible lineage-specific introgression events from the Eurasian lineages than from the American lineages. Our results expand the knowledge on ecology, genetic diversity, biogeography, and evolution of S. paradoxus.

Effect of Ropivacaine-Loaded Magnetic Nanoparticles on Ankle Nerve Block in Rats.

AIM: Our study is to determine the influence of ropivacaine-loaded magnetic nanoparticles (MNP/Rop) on ankle nerve block in rats. MATERIALS AND METHODS: MNP/Rop was prepared and then injected intravenously into rats to evaluate its anesthetic effect on rat limbs. Mechanical pain thresholds paw withdrawal threshold (PWT) and paw withdrawal thermal latency (PWL) were employed for the assessment of ankle nerve block in rats. RESULTS: PWT increased from T1 to T4 in each group (P < 0.05). The intergroup comparison determined no distinct difference in the PWT value among the three series at T1 (P > 0.05); however, PWT values at T2-T4 were higher in nerve block control group (NBCG) and MNP/Rop group than in blank group (BG), and they remained slightly higher in MNP/Rop group than in NBCG. The intragroup comparison revealed that from T1 to T4, PWL in each group showed a rising trend. The PWL at T1 showed no evident difference among the three series (P > 0.05); however, PWL values at T2-T4 were higher in NBCG and MNP/Rop group than in BG, and they remained slightly higher in MNP/Rop group than in NBCG. In MNP/Rop group, both PWT and PWL increased with the increase of Fe3O4 load in MNP/Rop (P < 0.05), while PWT and PWL remained unchanged when the load was 2.189%; moreover, PWT and PWL elevated as Rop concentration increased in MNP/Rop (P < 0.05), while they kept unaltered under 40 µL 1% Rop. CONCLUSION: Intravenous injection of MNP/Rop into rats and inhalation of MNP into the ankle joint can effectively block ankle nerve conduction in rats.

Novel Hybrid Peptide Cathelicidin 2 (1-13)-Thymopentin (TP5) and Its Derived Peptides with Effective Antibacterial, Antibiofilm, and Anti-Adhesion Activities.

The increasing numbers of infections caused by multidrug-resistant (MDR) pathogens highlight the urgent need for new alternatives to conventional antibiotics. Antimicrobial peptides have the potential to be promising alternatives to antibiotics because of their effective bactericidal activity and highly selective toxicity. The present study was conducted to investigate the antibacterial, antibiofilm, and anti-adhesion activities of different CTP peptides (CTP: the original hybrid peptide cathelicidin 2 (1-13)-thymopentin (TP5); CTP-NH2: C-terminal amidated derivative of cathelicidin 2 (1-13)-TP5; CTPQ: glutamine added at the C-terminus of cathelicidin 2 (1-13)-TP5) by determining the minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), propidium iodide uptake, and analysis by scanning electron microscopy, transmission electron microscopy, and confocal laser scanning microscopy). The results showed that CTPs had broad-spectrum antibacterial activity against different gram-positive and gram-negative bacteria, with MICs against the tested strains varying from 2 to 64 µg/mL. CTPs at the MBC (2 × MIC 64 µg/mL) showed strong bactericidal effects on a standard methicillin-resistant Staphylococcus aureus strain ATCC 43300 after co-incubation for 6 h through disruption of the bacterial membrane. In addition, CTPs at 2 × MIC also displayed effective inhibition activity of several S. aureus strains with a 40-90% decrease in biofilm formation by killing the bacteria embedded in the biofilms. CTPs had low cytotoxicity on the intestinal porcine epithelial cell line (IPEC-J2) and could significantly decrease the rate of adhesion of S. aureus ATCC 43300 on IPEC-J2 cells. The current study proved that CTPs have effective antibacterial, antibiofilm, and anti-adhesion activities. Overall, this study contributes to our understanding of the possible antibacterial and antibiofilm mechanisms of CTPs, which might be an effective anti-MDR drug candidate.

In-Situ Isothermal Crystallization of Poly(l-lactide).

The isothermal crystallization of poly(l-lactide) (PLLA) has been investigated by in-situ wide angle X-ray diffraction (WAXD) and polarized optical microscopes (POM) equipped with a hot-stage accessory. Results showed that the spherulites of PLLA were formed at high temperature, whereas irregular morphology was observed under a low temperature. This can be attributed to the varying rates of crystallization of PLLA at different temperatures. At low temperatures, the nucleation rate is fast and hence the chains diffuse very slow, resulting in the formation of imperfect crystals. On the other hand, at high temperatures, the nucleation rate is slow and the chains diffuse fast, leading to the formation of perfect crystals. The change in the value of the Avrami exponent with temperature further verifies the varying trend in the morphological feature of the crystals.