Impact of Respiratory Bacterial Findings on Patients with Chronic Pulmonary Aspergillosis.

Background: Distinct bacterial strains may affect the prognosis of patients with chronic respiratory diseases. However, little is known about the clinical significance of respiratory bacteria in patients with chronic pulmonary aspergillosis (CPA), a progressive and debilitating disease caused by Aspergillus spp. Objectives: This study aimed to analyze data obtained from CPA patients and their sputum or bronchial washing samples and investigate the prevalence and composition of respiratory bacteria and clinical implications. Patients and Methods. We retrospectively reviewed the data of patients diagnosed with CPA between March 2019 and February 2023 in a tertiary referral hospital. We assessed the clinical characteristics and overall and pneumonia-specific survival rates of patients with CPA based on the presence of bacteria. Results and Conclusions. We included 142 patients with CPA. The most commonly identified bacteria were Klebsiella pneumoniae (22.5%), followed by Pseudomonas aeruginosa (21.8%) and Escherichia coli (4.2%). Patients with isolated bacteria had a higher prevalence of older age, female sex, diabetes, and a history of extrathoracic malignancy than those without isolated bacteria (P = 0.024, 0.013, 0.021, and 0.034, respectively). Furthermore, over a median follow-up of 11 (4-21) months, the pneumonia-specific mortality rate was 13.4% (19/142), which was higher in patients with isolated bacteria than in those without (P = 0.045, log-rank test). Particularly, patients with the presence of P. aeruginosa had a significantly higher mortality rate from pneumonia than those without the presence of P. aeruginosa (adjusted hazard ratio, 3.34; P = 0.015). In conclusion, CPA patients with isolated bacteria, especially P. aeruginosa, showed higher mortality rates due to pneumonia. Performing tests to identify bacteria in the lower respiratory tract of patients with CPA may be helpful in predicting future prognosis. Further studies are required to validate these findings in diverse ethnic groups.

H1N1 nanobody development and therapeutic efficacy verification in H1N1-challenged mice.

Influenza A virus causes numerous deaths and infections worldwide annually. Therefore, we have considered nanobodies as a potential treatment for patients with severe cases of influenza. We developed a nanobody that was expected to have protective efficacy against the A/California/04/2009 (CA/04; pandemic 2009 flu strain) and evaluated its therapeutic efficacy against CA/04 in mice experiments. This nanobody was derived from the immunization of the alpaca, and the inactivated CA/04 virus was used as an immunogen. We successfully generated a nanobody library through bio-panning, phage ELISA, and Bio-layer interferometry. Moreover, we confirmed that administering nanobodies after lethal doses of CA/04 reduced viral replication in the lungs and influenza-induced clinical signs in mice. These research findings will help to develop nanobodies as viral therapeutics for CA/04 and other infectious viruses.

Clinical scoring model for predicting cefotaxime-resistance in Klebsiella pneumoniae bacteremia: development and validation based on portal of entry.

We developed a prediction model for cefotaxime resistance in patients with K. pneumoniae bacteremia. Adult patients with K. pneumoniae bacteremia were grouped into derivation (from March 2018 to December 2019) and validation (from January 2020 to August 2020) cohorts. The prediction scoring system was based on factors associated with cefotaxime resistance identified by the logistic regression model. A total of 358 patients were enrolled (256 for derivation, 102 for validation). In the multivariable analysis, age ≥65 years, hospital-acquired infection, prior antimicrobial use, and an updated Charlson comorbidity index ≥3 points were associated with cefotaxime resistance in the derivation cohort. When each variable was counted as 1 point, the values of the area under the curve were 0.761 in the derivation and 0.781 in the validation cohorts. The best cutoff value using the Youden index was ≥2 with 73.6% sensitivity and 67.5% specificity. Our simple scoring system favorably predicted cefotaxime resistance.

Clinical outcomes and treatment necessity in patients with toxin-negative Clostridioides difficile stool samples.

PURPOSE: The clinical significance of negative toxin enzyme immunoassays (EIA) for Clostridioides difficile infections (CDIs) is unclear. Our study aimed to investigate the significance of toxin EIA-negative in the diagnosis and prognosis of CDI. METHODS: All stool specimens submitted for C. difficile toxin EIA testing were cultured to isolate C. difficile. In-house PCR for tcdA, tcdB, cdtA, and cdtB genes were performed using C. difficile isolates. Stool specimens were tested with C. difficile toxins A and B using EIA kit (RIDASCREEN Clostridium difficile toxin A/B, R-Biopharm AG, Darmstadt, Germany). Characteristics and subsequent CDI episodes of toxin EIA-negative and -positive patients were compared. RESULTS: Among 190 C. difficile PCR-positive patients, 83 (43.7%) were toxin EIA-negative. Multivariate analysis revealed independent associations toxin EIA-negative results and shorter hospital stays (OR = 0.98, 95% CI 0.96-0.99, p = 0.013) and less high-risk antibiotic exposure in the preceding month (OR = 0.38, 95% CI 0.16-0.94, p = 0.035). Toxin EIA-negative patients displayed a significantly lower white blood cell count rate (11.0 vs. 35.4%, p < 0.001). Among the 54 patients who were toxin EIA-negative and did not receive CDI treatment, three (5.6%) were diagnosed with CDI after 7-21 days without complication. CONCLUSION: Our study demonstrates that toxin EIA-negative patients had milder laboratory findings and no complications, despite not receiving treatment. Prolonged hospitalisation and exposure to high-risk antibiotics could potentially serve as markers for the development of toxin EIA-positive CDI.

ARTS and small-molecule ARTS mimetics upregulate p53 levels by promoting the degradation of XIAP.

Mutations resulting in decreased activity of p53 tumor suppressor protein promote tumorigenesis. P53 protein levels are tightly regulated through the Ubiquitin Proteasome System (UPS). Several E3 ligases were shown to regulate p53 stability, including MDM2. Here we report that the ubiquitin E3 ligase XIAP (X-linked Inhibitors of Apoptosis) is a direct ligase for p53 and describe a novel approach for modulating the levels of p53 by targeting the XIAP pathway. Using in vivo (live-cell) and in vitro (cell-free reconstituted system) ubiquitylation assays, we show that the XIAP-antagonist ARTS regulates the levels of p53 by promoting the degradation of XIAP. XIAP directly binds and ubiquitylates p53. In apoptotic cells, ARTS inhibits the ubiquitylation of p53 by antagonizing XIAP. XIAP knockout MEFs express higher p53 protein levels compared to wild-type MEFs. Computational screen for small molecules with high affinity to the ARTS-binding site within XIAP identified a small-molecule ARTS-mimetic, B3. This compound stimulates apoptosis in a wide range of cancer cells but not normal PBMC (Peripheral Blood Mononuclear Cells). Like ARTS, the B3 compound binds to XIAP and promotes its degradation via the UPS. B3 binding to XIAP stabilizes p53 by disrupting its interaction with XIAP. These results reveal a novel mechanism by which ARTS and p53 regulate each other through an amplification loop to promote apoptosis. Finally, these data suggest that targeting the ARTS binding pocket in XIAP can be used to increase p53 levels as a new strategy for developing anti-cancer therapeutics.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.