Ineffectiveness of colistin monotherapy in treating carbapenem-resistant Acinetobacter baumannii Pneumonia: A retrospective single-center cohort study.

BACKGROUND: Acinetobacter baumannii, a common carbapenem-resistant gram-negative bacillus, usually causes nosocomial infections. Colistin has been used for carbapenem-resistant A. baumannii (CRAB) infections; however, only a few studies have evaluated colistin as a treatment option compared to appropriate controls. We investigated the effectiveness of colistin monotherapy in treating CRAB pneumonia compared to those treated without an active drug. METHODS: Adult patients (≥ 18 years) with CRAB isolated from respiratory specimens were screened from September 2017 to August 2022. Only patients with pneumonia treated with colistin monotherapy (colistin group) were included and compared to those without any active antibiotics (no active antibiotics [NAA] group). The primary and secondary outcomes were 30-day all-cause mortality and acute kidney injury within 30 days. The inverse probability of the treatment-weighted Cox proportional hazard model was used to compare mortality between groups. RESULTS: Among the 826 adult patients with CRAB in their respiratory specimens, 45 and 123 patients were included in the colistin and NAA groups, respectively. Most of the CRAB pneumonia (91.1%) cases were hospital-acquired pneumonia. The 30-day all-cause mortality rates in the colistin and NAA groups were 58.3% and 56.1%, respectively, and no difference was observed after adjustments (adjusted hazard ratio, 0.74; 95% CI, 0.47-1.17). The incidence of acute kidney injury was higher in the colistin group (65.3%) compared to the NAA group (39.0%) (P = 0.143). CONCLUSIONS: Colistin monotherapy did not significantly improve treatment outcomes for CRAB pneumonia. The development and evaluation of new antimicrobials for CRAB pneumonia should be advocated in clinical practice.

The complete chloroplast genome of the neo-allotetraploid fern, Asplenium pseudocapillipes S.H.Park et al. (Aspleniaceae).

This study analyzed the complete plastome sequence of the neo-allotetraploid Asplenium pseudocapillipes S.H.Park et al. Asplenium pseudocapillipes has a typical circular plastome that comprises 157,242 bp with a large single copy (84,105 bp), a small single copy (21,503 bp), and two inverted repeats (IRs; 25,817 bp). The complete sequence comprises 127 genes, including 87 protein-coding genes (CDSs), eight ribosomal RNAs (rRNAs), 31 transfer RNAs (tRNAs), and one pseudogene. Among these genes, five CDSs, four rRNAs, and five tRNAs are duplicated in IRs. The guanine-cytosine content of the genome was 41.5%. The enlarged noncoding regions by Mobile Open Reading Frames in Fern Organelles were found once in other Asplenium species and twice in A. pseudocapillipes. Phylogenetic analysis based on 83 coding gene sequences revealed that A. pseudocapillipes is embedded in the A. varians subclade along with its progenitors.

Treatment of Soft Tissue Defects after Minimally Invasive Plate Osteosynthesis in Fractures of the Distal Tibia: Clinical Results after Reverse Sural Artery Flap.

Introduction: Distal tibial fractures make up approximately 3% to 10% of all tibial fractures or about 1% of lower extremity fractures. MIPO is an appropriate procedure and method to achieve stable metal plate fixation and osseointegration by minimizing soft tissue damage and vascular integrity at the fracture site. MIPO to the medial tibia during distal tibial fractures induces skin irritation due to the thickness of the metal plate, which causes discomfort and pain on the medial side of the distal leg, and if severe, complications such as infection and skin defect may occur. The reverse sural flap is a well-researched approach for covering defects in the lower third of the leg, ankle, and foot. Materials and Methods: Among 151 patients with distal tibia fractures who underwent minimally invasive metal plate fixation, soft tissue was injured due to postoperative complications. We treated 13 cases with necrosis and exposed metal plates by retrograde nasogastric artery flap surgery. For these patients, we collected obligatory patient records, radiological data, and wound photographs of the treatment results and complications of reconstructive surgery. Results: In all the cases, flap survival was confirmed at the final outpatient follow-up. The exposed area of the metal plate was well coated, and there was no plate failure due to complete necrosis. Three out of four women complained of aesthetic dissatisfaction because the volume of the tunnel through which the skin mirror passed and the skin plate itself were thick. In two cases, defatting was performed to reduce the thickness of the plate while removing the metal plate. Conclusions: Metal plate exposure after distal tibial fractures have been treated with minimally invasive metal plate fusion and can be successfully treated with retrograde nasogastric artery flaps, and several surgical techniques are used during flap surgery.

Trametinib activates endogenous neurogenesis and recovers neuropathology in a model of Alzheimer's disease.

Enhancing adult neurogenesis in the brain has been suggested as a potential therapeutic strategy for AD. We developed a screening platform, ATRIVIEW®, for molecules that activate neuronal differentiation of adult mouse NSCs. The most potent hit from an FDA-approved drug library was SNR1611 (trametinib), a selective MEK1/2 inhibitor. We found that trametinib increases the levels of P15INK4b and Neurog2, suggesting a mechanism by which MEK1/2 inhibition induces neuronal differentiation. Oral administration of trametinib increased adult neurogenesis in the dentate gyrus and subventricular zone of the 5XFAD AD mouse model. Surprisingly, we also found that trametinib enhanced adult neurogenesis in the cortex. Consequently, trametinib rescued AD pathologies such as neuronal loss and cognitive impairment in 5XFAD mice. Finally, trametinib induced neurogenic differentiation of NSCs derived from AD patient iPSCs, which suggests its potential therapeutic application. Altogether, we suggest that restoration of endogenous adult neurogenesis by trametinib may be a promising therapeutic approach to AD.

Complete chloroplast genome of Austral king fern Todea barbara (L.) Moore (Osmundaceae).

In this study, we determined the chloroplast genome sequence of the Austral king fern, Todea barbara (L.) Moore. The plastome of T. barbara is a typical circular form composed of 144,208 bp with two inverted repeats (IRs; 10,442 bp), a large single copy (LSC; 101,059 bp), and a small single copy (SSC; 22,265 bp). The complete sequence comprises 131 genes, namely 85 protein-coding genes, eight ribosomal RNAs, and 38 transfer RNAs. The guanine-cytosine (GC) content of the genome was found to be 39.9%. Additionally, U-to-C RNA editing sites were identified in eight genes: atpE, chlB, clpP, matK, rpl20, rpoB, rpoC1, and rpoC2. Phylogenetic analysis using 85 coding gene sequences revealed that the genera Todea and Osmunda form a clade and that the genus Osmundastrum is a sister genus to both.

The complete chloroplast genome sequence of Crepidomanes latealatum (Bosch) Copel.

The complete chloroplast genome sequence of Crepidomanes latealatum (Bosch) Copel. was determined in the present study. The genome is 145,943 base pairs (bp) in length and comprised two inverted repeats (32,990 bp) between a large single copy (92,170 bp) and a small single copy (20,783 bp). It contains 88 coding genes, 8 rRNA genes, 34 tRNA genes, and 1 pseudogene of trnL-UAA, and the GC content is 37.6%. Molecular phylogenetic analysis based on the plastid genome sequences of related taxa strongly supported the monophyly of the family Hymenophyllaceae, and the genus Vandenboschia was a sister group of Crepidomanes. In addition, compared to C. minutum, two large deletions of 453 bp and 878 bp were found in the IGS regions of petA-psbI and rrn16-trnV-GAC of C. latealatum cp genome, respectively.

Dynamic hybridization between two spleenworts, Asplenium incisum and Asplenium ruprechtii in Korea.

Natural hybridization between Asplenium incisum and A. ruprechtii has been observed in Northeast Asia and its allotetraploid species, A. castaneoviride, was reported. However, the hybridization process between the parental species and the origin of the allotetraploid taxon remains obscure. Additionally, the systematic affinities of the recently described hybrid A. bimixtum, considered to have originated from the hybridization of A. ruprechtii, A. trichomanes, and A. incisum, is unresolved owing to its similarity to A. castaneoviride. The goals of this study were to (1) investigate the hybridization between A. ruprechtii and A. incisum; (2) verify the origin of A. castaneoviride occurring in Korea, whether it independently arose from 2x sterile hybrids; and (3) elucidate the reliability of identifying A. bimixtum. Three genotypes, A. incisum, A. ruprechtii, and their hybrid, were identified based on the nuclear gene pgiC sequence and finally divided them into six types by ploidy levels: diploid A. incisum, A. ruprechtii, and four hybrid types (diploid A. × castaneoviride, triploid A. × castaneoviride, allotetraploid A. castaneoviride, and A. bimixtum). In the analyses of plastid DNA, all hybrids had an A. ruprechtii-type rbcL gene. In addition, the four plastomes of A. ruprechtii and the hybrids had high pairwise sequence identities greater than 98.48%. They increased up to 99.88% when a large deletion of A. x castaneoriviride (2x) collected from Buramsan populations was ignored. Notably, this large deletion was also found in triploid A. × castaneoviride and allotetraploid A. castaneoviride in the same populations. Sequence data of the nuclear and plastid genes showed that hybridization is unidirectional, and A. ruprechtii is the maternal parent. The large deletion of rpoC2-rps2 commonly found in the different ploidy hybrids of the Buramsan population suggests that the allotetraploid A. castaneoviride can be created independently from sterile hybrids. We assume that both polyploidization driving allopolyploidy and minority cytotype exclusion took place independently in the population, since A castaenoviride co-occurs with A. ruprechtii in small populations. Furthermore, it was also observed that an enlarged noncoding region in fern organelle (ENRIFO) of the plastome was found in the genus Asplenium.

The complete chloroplast genome sequence of the Korean maple tree (Acer pseudosieboldianum (Pax) Kom.).

The complete chloroplast genome sequence of Acer pseudosieboldianum (Sapindaceae) was determined. The chloroplast genome of A. pseudosieboldianum is 157,053 bp in length with two inverted repeats (26,747 bp) between a large single-copy (85,391 bp) and a small single-copy (18,168 bp). The GC content was 37.8% and it was composed of 86 coding genes, eight rRNA genes, 37 tRNA genes, and two pseudogenes, rps2, and ycf1. Molecular phylogenetic analysis based on the plastid genome sequences strongly supported the hypothesis that A. pseudosieboldianum was embedded in the series Palmata of section Palmata. However, the phylogenetic positions of A. ukurunduense and A. buergerianum, which are a members of the series Penninervia of sections Palmata and Pentaphylla, respectively, were incongruent with the recent sectional classification system.

PM2.5 exposure regulates Th1/Th2/Th17 cytokine production through NF-κB signaling in combined allergic rhinitis and asthma syndrome.

BACKGROUND: Particulate matter (PM) is a major component of air pollution from emissions from anthropogenic and natural sources and is a serious problem worldwide due to its adverse effects on human health. Increased particulate air pollution increases respiratory disease-related mortality and morbidity. However, the impact of PM with an aerodynamic diameter of ≤ 2.5 µm (PM2.5) on combined allergic rhinitis and asthma syndrome (CARAS) remains to be elucidated. Accordingly, in the present study, we investigated the effect of PM2.5 in an ovalbumin (OVA)-induced CARAS mouse model with a focus on NF-κB signaling. METHODOLOGY: We established an OVA-induced mouse model of CARAS to determine the effects of exposure to PM2.5. BALB/c mice were randomly divided into four groups: (1) naive, (2) PM2.5, (3) CARAS, and (4) CARAS/PM2.5. Mice were systemically sensitized with OVA and challenged with inhalation of ultrasonically nebulized 5% OVA three times by intranasal instillation of OVA in each nostril for 7 consecutive days. Mice in the PM2.5 and CARAS/PM2.5 groups were then exposed to PM2.5 by intranasal instillation of PM2.5 for several days. We then examined the impacts of PM2.5 exposure on histopathology and NF-κB signaling in our OVA-induced CARAS mouse model. RESULTS: PM2.5 increased infiltration of eosinophils in bronchoalveolar lavage fluid (BALF) samples and inflammatory cells in lung tissue. It also increased production of GATA3, RORγ, IL-4, IL-5, IL-13, and IL-17 in nasal lavage fluid (NALF) and BALF samples in the CARAS mouse model, but secretion of IL-12 and IFN-γ was suppressed. Exposure to PM2.5 increased OVA-specific IgE and IgG1 levels in serum, inflammatory cell infiltration in the airways, and fibrosis in lung tissue. It also activated the NF-κB signaling pathway, increasing Th2/Th17 cytokine levels while decreasing Th1 cytokine expression, thereby inducing an inflammatory response and promoting inflammatory cell infiltration in nasal and lung tissue. CONCLUSION: Our results demonstrate that PM2.5 can aggravate OVA-induced CARAS.

Femoral head cartilage reconstruction using autologous osteochondral mosaicplasty: A case report.

RATIONALE: Cartilage injuries of the femoral head may occur following hip dislocation. As a rare injury, controversy persists regarding ideal treatment of damaged femoral head cartilage. Here we report the case of a patient who developed a large cartilage injury to the femoral head following anterior hip dislocation for which autologous osteochondral mosaicplasty with a graft harvested from the ipsilateral femoral head achieved a satisfactory outcome. PATIENT CONCERNS: A 62-year-old man developed a right hip dislocation after a fall from a 5-m height and was referred to our institution. DIAGNOSES: The initial diagnosis was anterior hip dislocation. Upon hip joint reduction, a simple radiograph and computed tomography scan showed a large cartilage defect in the superolateral region of the femoral head. Multiple bony fragments were visible within the joint. INTERVENTIONS: The hip joint was surgically dislocated. The large cartilage defect of the femoral head was treated with autologous mosaicplasty using an osteochondral autograft transfer system using multiple osteochondral plugs retrieved from a non-weight-bearing portion of the ipsilateral femoral head. OUTCOMES: Diagnostic hip arthroscopy performed at 8 months postoperative confirmed full incorporation of the osteochondral graft into the native femoral head. At the 2-year follow-up, the patient was pain-free, had a normal range of motion and displayed no evidence of osteoarthritis. LESSONS: Isolated femoral head cartilage injuries may occur as a consequence of anterior hip dislocation. A femoral head with a large irregular cartilage defect can be treated with mosaicplasty using an osteochondral autograft from a non-weight-bearing portion of the ipsilateral femoral head.

Multifaceted Evaluation of Antibiotic Therapy as a Factor Associated with Candidemia in Non-Neutropenic Patients.

We aimed to evaluate various aspects of antibiotic therapy as factors associated with candidemia in non-neutropenic patients. A retrospective, matched, case-control study was conducted in two teaching hospitals. Patients with candidemia (cases) were compared to patients without candidemia (controls), matched by age, intensive care unit admission, duration of hospitalization, and type of surgery. Logistic regression analyses were performed to identify factors associated with candidemia. A total of 246 patients were included in the study. Of 123 candidemia patients, 36% had catheter-related bloodstream infections (CRBSIs). Independent factors in the whole population included immunosuppression (adjusted odds ratio [aOR] = 2.195; p = 0.036), total parenteral nutrition (aOR = 3.642; p < 0.001), and anti-methicillin-resistant S. aureus (MRSA) therapy for ≥11 days (aOR = 5.151; p = 0.004). The antibiotic factor in the non-CRBSI population was anti-pseudomonal beta-lactam treatment duration of ≥3 days (aOR = 5.260; p = 0.008). The antibiotic factors in the CRBSI population included anti-MRSA therapy for ≥11 days (aOR = 10.031; p = 0.019). Antimicrobial stewardship that reduces exposure to these antibacterial spectra could help prevent the development of candidemia.

Clinical characteristics and manifestations in patients with hypermucoviscous Klebsiella pneumoniae bacteremia from extra-hepatobiliary tract infection.

PURPOSE: Hypermucoviscous strains of Klebsiella pneumoniae (KP) are associated with invasive liver abscess syndrome. However, little is known about the characteristics of this phenotype in non-hepatobiliary infections. In this study, we investigated the clinical characteristics of patients with hypermucoviscous Kp (hmvKp) bacteremia from non-hepatobiliary tract infection. METHODS: This retrospective cohort study was implemented at Samsung Changwon Hospital. From March 2018 to December 2019, adult patients (≥ 18 years) with KP bacteremia of the extra-hepatobiliary system were enrolled. Hypermucoviscosity was defined by the string test. Clinical characteristics and 30-day all-cause mortality between patients with hmvKp and non-hmvKp bacteremia were compared. RESULTS: Among 179 cases of non-hepatobiliary KP bacteremia, 67 (37.4%) and 112 (62.6%) isolates were classified as hmvKp and non-hmvKp, respectively. In the hmvKp group, metastatic infection (9.0 vs. 1.8%, P = 0.054) and purulent or necrotizing infection (31.3 vs. 9.8%, P < 0.001) were more frequently observed. Additionally, non-hmvKp had more frequent resistance to cefotaxime (11.9 vs. 38.4%, P < 0.001). Thirty-day all-cause mortality was similar in the hmvKp (41.8%) and non-hmvKp (39.3%) groups (P = 0.643). In multivariable analysis, septic shock (adjusted hazard ratio [aHR] = 3.05, 95% confidence interval [CI]: 1.22-7.63) and Pitt bacteremia score (aHR = 1.23 per 1 point, 95% CI 1.14-1.33) were associated with increased mortality in patients with Kp bacteremia, while urinary-tract infection (aHR = 0.38, 95% CI 0.18-0.76) was associated with decreased mortality. CONCLUSION: hmvKp was associated with less frequent drug resistance and metastatic-purulent presentation in non-hepatobiliary infection like in hepatobiliary infection. However, hmvKp was not associated with clinical outcomes.

Asplenium pseudocapillipes (Aspleniaceae), a New Fern Species from South Korea.

A new allotetraploid species of the genus Asplenium, A. pseudocapillipes, originated from the hybridization between A. capillipes and A. tenuicaule, has been newly discovered in two limestone areas of South Korea. A molecular phylogenetic analysis using one chloroplast region (rbcL) and three single- or low-copy nuclear regions (AK1, gapCp, pgiC) and a cytological analysis, including genome size measurements, were conducted to characterize this new species. From these results, the maternal origin of A. pseudocapillipes was confirmed to be A. capillipes, which has never been reported in Korea. All three nuclear data showed that this new species had genotypes of both A. capillipes and A. tenuicaule. The quantitative characteristics of the leaves showed values intermediate between the two parental species. The absence of gemma accorded with its paternal origin from A. tenuicaule, and 32 spores per sporangium accorded with its maternal origin from A. capillipes. Although A. pseudocapillipes has 32 spores per sporangium, it is considered to be a sexually reproducing, not an apomitic, fern.

The complete chloroplast genome of Ziziphus jujuba cv. Bokjo (Rhamnaceae).

We have sequenced the Ziziphus jujuba cv. Bokjo chloroplast genome by de novo assembly using next-generation sequencing. The complete circular chloroplast genome consisted of 161,714 bp and contained four parts: a large single-copy (LSC) region of 89,323 bp, a small single-copy (SSC) region of 19,361 bp, and two inverted repeat regions (IRa and IRb) of 26,515 bp each. The genome annotation predicted a total of 110 genes, including 76 protein-coding genes, 30 tRNA genes, and four rRNA genes. Phylogenetic analysis demonstrated the close taxonomic relationship between Z. jujuba cv. Bokjo and two other members of the Ziziphus genus, Z. spina-christi and Z. mauritiana. We found 135 polymorphic loci, 63 single nucleotide polymorphism (SNP) and 72 insertion-deletion (InDel), from the comparison of Z. jujuba cultivar Bokjo and Z. jujuba reference (NC_030299). The polymorphic loci could be used for the differentiation of Z. jujuba genetic resources and for breeding in the future.

MEK1/2 inhibition rescues neurodegeneration by TFEB-mediated activation of autophagic lysosomal function in a model of Alzheimer's Disease.

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder, which is characterized by cognitive deficit due to synaptic loss and neuronal death. Extracellular amyloid ß plaques are one of the pathological hallmarks of AD. The autophagic lysosomal pathway is the essential mechanism to maintain cellular homeostasis by driving clearance of protein aggregates and is dysfunctional in AD. Here, we showed that inhibiting MEK/ERK signaling using a clinically available MEK1/2 inhibitor, trametinib (GSK1120212, SNR1611), induces the protection of neurons through autophagic lysosomal activation mediated by transcription factor EB (TFEB) in a model of AD. Orally administered trametinib recovered impaired neural structures, cognitive functions, and hippocampal long-term potentiation (LTP) in 5XFAD mice. Trametinib also reduced Aß deposition via induction of autophagic lysosomal activation. RNA-sequencing analysis revealed upregulation of autophagic lysosomal genes by trametinib administration. In addition, trametinib inhibited TFEB phosphorylation at Ser142 and promoted its nuclear translocation, which in turn induced autophagic lysosomal related genes, indicating that trametinib activates the autophagic lysosomal process through TFEB activation. From these observations, we concluded that MEK inhibition provides neuronal protection from the Aß burden by increasing autophagic lysosomal activity. Thus, MEK inhibition may be an effective therapeutic strategy for AD.

The epidemiology of bloodstream infection contributing to mortality: the difference between community-acquired, healthcare-associated, and hospital-acquired infections.

BACKGROUND: The epidemiology of bloodstream infection (BSI) is well-established; however, little is known about the contribution of different pathogens to mortality. To understand true burden of BSI, pathogens contributing to mortality were investigated and compared according to where the BSI was acquired. METHODS: Data from deceased patients in two teaching hospitals in the Republic of Korea were collected. BSI contributing mortality was defined as BSI within 2-weeks before death. Cases were grouped by acquisition sites: community-acquired (CA)-, healthcare-associated (HCA)-, and hospital-acquired (HA)-BSI. Drug resistance, BSI focus, and appropriateness of empirical antimicrobial therapy were also compared. RESULTS: Among 1849 deceased patients in the hospitals, 280 (15.1%) patients experienced BSI within 2-weeks before death. In all, 71, 53, and 156 patients in the CA-, HCA-, and HA-BSI groups, respectively, with 316 total isolated pathogens were analyzed. The three most common pathogens were Klebsiella pneumoniae (17.1%), Escherichia coli (16.4%), and Staphylococcus aureus (11.4%). While K. pneumoniae and E. coli were the most common pathogens in CA- and HCA-BSI, Acinetobacter baumannii and Candida species were in HA-BSI. 26.3% (41/156) of patients experienced breakthrough HCA-BSI during administration of carbapenem and/or vancomycin. The proportion of central venous catheter-related infection (0%, 3.4% and 28.3%), carbapenem resistant-Gram negative bacilli (0%, 6.9% and 21.9%), and inappropriate empirical antimicrobial therapy (21.1%, 37.7% and 51.9%; all P < 0.001) were more frequently observed in HA-BSI. CONCLUSION: The epidemiology of BSI related to mortality had unique characteristics according to the acquisition site. Given the epidemiology of HA-BSI, infection control and antibiotics stewardship programs should be emphasized.

Predictive Factors of Severe Dissection after Balloon Angioplasty for Femoropopliteal Artery Disease.

BACKGROUND: Arterial dissection is one of the mechanisms of balloon angioplasty. Although some degree of dissection is unavoidable, severe dissection that impedes blood flow decreases patency and increases the need for additional procedures. To improve the results of angioplasty, it is necessary to understand the factors related to severe dissection and make efforts to reduce its occurrence. This study aimed to elucidate the predictive and protective factors associated with severe dissection in femoropopliteal balloon angioplasty. METHODS: This was a retrospective, single-center, nonrandomized study. A total of 409 limbs were studied in 334 patients with symptomatic femoropopliteal lesions treated between 2010 and 2019. Dissections after initial balloon angioplasty were classified according to the Kobayashi dissection classification (grade A: no dissection; B: mild dissection <1/3 of the lumen; C: severe dissection, ≥1/3 of the lumen) into the nonsevere dissection group (grades A and B), and severe dissection group (grade C). We compared clinical, procedural and lesion-related characteristics between the 2 groups. Factors with statistical significance in univariate analyses were entered into a multivariate logistic regression model to identify independent predictive factors of severe dissection. RESULTS: Severe dissection occurred in 237 limbs and nonsevere dissection in 172 limbs. In univariate analyses, the predictive factors of severe dissection were TransAtlantic Inter-Society Consensus II C/D grades (P < 0.001), lesion length ≥15cm (P < 0.001), chronic total occlusion (P = 0.004), and degree of stenosis ≥70% (P < 0.001). Protective factors for severe dissection were end-stage renal disease (P = 0.008), severe calcification >50% (P < 0.001), and the use of a scoring balloon (P = 0.001). In multivariate analysis, factors associated with severe dissection were lesion length ≥15cm (OR, 2.259; 95% CI: 1.417-4-3.601), occlusion or degree of stenosis ≥70% (OR, 1.931; 95% CI: 1.255-2.971), severe calcification (OR, 0.520; 95% CI: 0.338-0.800), and the use of a scoring balloon (OR, 0.467; 95% CI: 0.263-0.830). CONCLUSIONS: Lesion length ≥15cm and occlusion or stenosis ≥70% were identified as independent predictive factors of severe dissection in femoropopliteal artery balloon angioplasty. Conversely, severe calcification and the use of a scoring balloon appeared to be protective factors against severe dissection.

PM2.5 Exacerbates Oxidative Stress and Inflammatory Response through the Nrf2/NF-κB Signaling Pathway in OVA-Induced Allergic Rhinitis Mouse Model.

Air pollution-related particulate matter (PM) exposure reportedly enhances allergic airway inflammation. Some studies have shown an association between PM exposure and a risk for allergic rhinitis (AR). However, the effect of PM for AR is not fully understood. An AR mouse model was developed by intranasal administration of 100 µg/mouse PM with a less than or equal to 2.5 µm in aerodynamic diameter (PM2.5) solution, and then by intraperitoneal injection of ovalbumin (OVA) with alum and intranasal challenging with 10 mg/mL OVA. The effects of PM2.5 on oxidative stress and inflammatory response via the Nrf2/NF-κB signaling pathway in mice with or without AR indicating by histological, serum, and protein analyses were examined. PM2.5 administration enhanced allergic inflammatory cell expression in the nasal mucosa through increasing the expression of inflammatory cytokine and reducing the release of Treg cytokine in OVA-induced AR mice, although PM2.5 exposure itself induced neither allergic responses nor damage to nasal and lung tissues. Notably, repeated OVA-immunization markedly impaired the nasal mucosa in the septum region. Moreover, AR with PM2.5 exposure reinforced this impairment in OVA-induced AR mice. Long-term PM2.5 exposure strengthened allergic reactions by inducing the oxidative through malondialdehyde production. The present study also provided evidence, for the first time, that activity of the Nrf2 signaling pathway is inhibited in PM2.5 exposed AR mice. Furthermore, PM2.5 exposure increased the histopathological changes of nasal and lung tissues and related the inflammatory cytokine, and clearly enhanced PM2.5 phagocytosis by alveolar macrophages via activating the NF-κB signaling pathway. These obtained results suggest that AR patients may experience exacerbation of allergic responses in areas with prolonged PM2.5 exposure.

Mechanisms That Activate 26S Proteasomes and Enhance Protein Degradation.

Although ubiquitination is widely assumed to be the only regulated step in the ubiquitin-proteasome pathway, recent studies have demonstrated several important mechanisms that regulate the activities of the 26S proteasome. Most proteasomes in cells are inactive but, upon binding a ubiquitinated substrate, become activated by a two-step mechanism requiring an association of the ubiquitin chain with Usp14 and then a loosely folded protein domain with the ATPases. The initial activation step is signaled by Usp14's UBL domain, and many UBL-domain-containing proteins (e.g., Rad23, Parkin) also activate the proteasome. ZFAND5 is a distinct type of activator that binds ubiquitin conjugates and the proteasome and stimulates proteolysis during muscle atrophy. The proteasome's activities are also regulated through subunit phosphorylation. Agents that raise cAMP and activate PKA stimulate within minutes Rpn6 phosphorylation and enhance the selective degradation of short-lived proteins. Likewise, hormones, fasting, and exercise, which raise cAMP, activate proteasomes and proteolysis in target tissues. Agents that raise cGMP and activate PKG also stimulate 26S activities but modify different subunit(s) and stimulate also the degradation of long-lived cell proteins. Both kinases enhance the selective degradation of aggregation-prone proteins that cause neurodegenerative diseases. These new mechanisms regulating proteolysis thus have clear physiological importance and therapeutic potential.

The complete chloroplast genome sequence of Haplopteris flexuosa (Fée) E.H. Crane.

The complete chloroplast genome sequence of Haplopteris flexuosa, a member of Vittarioideae (family Pteridaceae), was determined. The chloroplast genome of H. flexuosa was 165,664 bp in length with two inverted repeats (32,556 bp) between a large single copy (79,996 bp) and a small single copy (20,556 bp). The GC content was higher than that of related taxa H. elongate, and it was caused by high GC content of expanded regions by insertion of mobile open reading frames in fern organelles (MORFFO) found in the family Pteridaceae. And also, we found that rrn5-rps12 enlarged region of H. flexuosa was similar to MORFFOs of other Pteridaceae.