Protective Effects of Coptis chinensis Rhizome Extract and Its Constituents (Berberine, Coptisine, and Palmatine) against α-Synuclein Neurotoxicity in Dopaminergic SH-SY5Y Cells.

Parkinson's disease (PD) is a common neurodegenerative disease with progressive loss of dopaminergic neurons in substantia nigra and the presence of α-synuclein-immunoreactive inclusions. Gaucher's disease is caused by homozygous mutations in ß-glucocerebrosidase gene (GBA). GBA mutation carriers have an increased risk of PD. Coptis chinensis (C. chinensis) rhizome extract is a major herb widely used to treat human diseases. This study examined the association of GBA L444P mutation with Taiwanese PD in 1016 cases and 539 controls. In addition, the protective effects of C. chinensis rhizome extract and its active constituents (berberine, coptisine, and palmatine) against PD were assayed using GBA reporter cells, LC3 reporter cells, and cells expressing mutated (A53T) α-synuclein. Case-control study revealed that GBA L444P carriers had a 3.93-fold increased risk of PD (95% confidence interval (CI): 1.37-11.24, p = 0.006) compared to normal controls. Both C. chinensis rhizome extract and its constituents exhibited chemical chaperone activity to reduce α-synuclein aggregation. Promoter reporter and endogenous GBA protein analyses revealed that C. chinensis rhizome extract and its constituents upregulated GBA expression in 293 cells. In addition, C. chinensis rhizome extract and its constituents induced autophagy in DsRed-LC3-expressing 293 cells. In SH-SY5Y cells expressing A53T α-synuclein, C. chinensis rhizome extract and its constituents reduced α-synuclein aggregation and associated neurotoxicity by upregulating GBA expression and activating autophagy. The results of reducing α-synuclein aggregation, enhancing GBA expression and autophagy, and protecting against α-synuclein neurotoxicity open up the therapeutic potentials of C. chinensis rhizome extract and constituents for PD.

[A multicenter study of neonatal stroke in Shenzhen, China]. / 深圳市新生儿脑卒中多中心现况调查.

OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Effects of Self-Administered Acupressure on Fatigue Following Traumatic Brain Injury: A Randomized Controlled Trial.

BACKGROUND: Fatigue is a common symptom after a traumatic brain injury (TBI) and may persist for weeks or years. However, nonpharmacological management strategies for fatigue alleviations are almost nonexistent; thus, effective fatigue management programs are needed urgently. PURPOSES: We aimed to evaluate the effects of self-administered acupressure programs on post-TBI fatigue and heart rate variability and identify the possible correlation between the improvements in fatigue symptoms and the changes in heart rate variability. DESIGN: This randomized controlled trial included 2-point acupressure (TPA; n = 27), 5-point acupressure (FPA; n = 27), and usual care (UC, control; n = 27) groups who underwent several assessments before and after the study intervention. Heart rate variability was evaluated at baseline, weeks 2 and 3, and treatment completion. METHODS: The TPA and FPA groups self-administered acupressure (3 minutes per acupoint; bilateral), thrice daily for 4 weeks, whereas the UC group received routine treatment without acupressure. RESULTS: Both the TPA and FPA groups exhibited substantial improvements in fatigue symptoms compared with the baseline findings in the UC group. In addition, the TPA and FPA groups exhibited increased high-frequency power and mean number of times per hour in which the changes in successive normal sinus intervals (RR) gradually exceeded 50 ms (pNN50). Changes in high-frequency power and pNN50 were correlated with improvements in post-TBI fatigue symptoms. CONCLUSION: Acupressure may alleviate chronic fatigue and enhance parasympathetic activity in TBI survivors. The enhancement of parasympathetic activity may be correlated with improvements in post-TBI fatigue symptoms. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers should incorporate self-administered acupressure into the care plans for TBI survivors to improve their fatigue symptoms.

[Effect of nanoparticles of different stiffness combined with menthol/curcumol on mechanical properties of bEnd.3 cells].

This study aimed to investigate the effects of nanoparticles PLGA-NPs and mesoporous silicon nanoparticles(MSNs) of different stiffness before and after combination with menthol or curcumol on the mechanical properties of bEnd.3 cells. The particle size distributions of PLGA-NPs and MSNs were measured by Malvern particle size analyzer, and the stiffness of the two nanoparticles was quantified by atomic force microscopy(AFM). The bEnd.3 cells were cultured in vitro, and the cell surface morphology, roughness, and Young's modulus were examined to characterize the roughness and stiffness of the cell surface. The changes in the mechanical properties of the cells were observed by AFM, and the structure and expression of cytoskeletal F-actin were observed by a laser-scanning confocal microscope. The results showed that both nanoparticles had good dispersion. The particle size of PLGA-NPs was(98.77±2.04) nm, the PDI was(0.140±0.030), and Young's modulus value was(104.717±8.475) MPa. The particle size of MSNs was(97.47±3.92) nm, the PDI was(0.380±0.016), and Young's modulus value was(306.019±8.822) MPa. The stiffness of PLGA-NPs was significantly lower than that of MSNs. After bEnd.3 cells were treated by PLGA-NPs and MSNs separately, the cells showed fine pores on the cell surface, increased roughness, decreased Young's modulus, blurred and broken F-actin bands, and reduced mean gray value. Compared with PLGA-NPs alone, PLGA-NPs combined with menthol or curcumol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value. Compared with MSNs alone, MSNs combined with menthol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value, while no significant difference was observed in combination with curcumol. Therefore, it is inferred that the aromatic components can increase the intracellular uptake and transport of nanoparticles by altering the biomechanical properties of bEnd.3 cells.

Pathomechanism Characterization and Potential Therapeutics Identification for Parkinson's Disease Targeting Neuroinflammation.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons and the presence of α-synuclein-containing Lewy bodies. The unstructured α-synuclein forms insoluble fibrils and aggregates that result in increased reactive oxygen species (ROS) and cellular toxicity in PD. Neuroinflammation engaged by microglia actively contributes to the pathogenesis of PD. In this study, we showed that VB-037 (a quinoline compound), glycyrrhetic acid (a pentacyclic triterpenoid), Glycyrrhiza inflata (G. inflata, a Chinese herbal medicine), and Shaoyao Gancao Tang (SG-Tang, a formulated Chinese medicine) suppressed the nitric oxide (NO) production and interleukin (IL)-1ß maturation in α-synuclein-stimulated BV-2 cells. Mouse inflammation antibody array further revealed increased IL-1α, IL-1ß, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) expression in α-synuclein-inflamed BV-2 cells and compound pretreatment effectively reduced the expression and release of these pro-inflammatory mediators. The test compounds and herbal medicines further reduced α-synuclein aggregation and associated oxidative stress, and protected cells against α-synuclein-induced neurotoxicity by downregulating NLR family pyrin domain containing 1 (NLRP1) and 3 (NLRP3), caspase 1, IL-1ß, IL-6, and associated nuclear factor (NF)-κB inhibitor alpha (IκBα)/NF-κB P65 subunit (P65), c-Jun N-terminal kinase (JNK)/proto-oncogene c-Jun (JUN), mitogen-activated protein kinase 14 (P38)/signal transducer and activator of transcription 1 (STAT1) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathways in dopaminergic neurons derived from α-synuclein-expressing SH-SY5Y cells. Our findings indicate the potential of VB-037, glycyrrhetic acid, G. inflata, and SG-Tang through mitigating α-synuclein-stimulated neuroinflammation in PD, as new drug candidates for PD treatment.

Anti-p53 Autoantibody Detection in Automatic Glass Capillary Immunoassay Platform for Screening of Oral Cavity Squamous Cell Carcinoma.

The incidence of oral squamous cell carcinoma (OSCC), which is one of the most common cancers worldwide, has been increasing. Serum anti-p53 autoantibody is one of the most sensitive biomarkers for OSCC. Currently, the most commonly used method on clinical screening platforms is the enzyme-linked immunosorbent assay, owing to its high specificity and repeatability. However, conducting immunoassays on 96-well plates is typically time consuming, thereby limiting its clinical applications for fast diagnosis and immediate prognosis of rapidly progressive diseases. The present study performed immunoassays in glass capillaries of 1-mm internal diameter, which increases the surface to volume ratio of the reaction, to shorten the time needed for immunoassay. The immunoassay was automated while using linear motorized stages and a syringe pump. The results indicated that, when compared with the 96-well plate immunoassay, the glass capillary immunoassay decreased the reaction time from typical 120 min to 45 min, reduced the amount of reagent from typical 50 µL to 15 µL, and required only simple equipment setup. Moreover, the limit of detection for glass capillary anti-p53 autoantibody immunoassay was 0.46 ng mL-1, which is close to the 0.19 ng mL-1 value of the conventional 96-well plate assay, and the glass capillary method had a broader detection range. The apparatus was used to detect the serum anti-p53 autoantibody concentration in clinical patients and compare its results with the conventional 96-well plate method results, which suggested that both of the methods detect the same trend in the relative concentration of serum anti-p53 autoantibody in healthy individuals or patients with OSCC.

A new isoflavone glycoside from Abrus cantoniensis.

A new isoflavone glycoside named as 8-O-methylrelusin-7-O-ß-D-apifuranosyl-(1→2)-ß-D-glucopyranoside (1), together with two known compounds, 8-O-methylrelusin-7-O-ß-D-glucopyranoside (2) and isobiflorin (3), were isolated from Abrus cantoniensis. The structure of the new compound was elucidated on the basis of spectroscopic methods including extensive 1D NMR, 2D NMR, and HRESIMS. This is the first report of isoflavone from Abrus cantoniensis. Moreover, all isolated compounds were evaluated for their cytotoxicity against SMMC-7721 and MHCC97-H cell lines.[Formula: see text].

Effects of normoxic and hypoxic exercise regimens on lymphocyte apoptosis induced by oxidative stress in sedentary males.

PURPOSE: Oxidative stress-induced lymphocyte apoptosis is linked to hypoxemic individuals suffering from cardiopulmonary disorders or exposed to hypoxic environments. What kind of the exercise strategy under hypoxic condition improves exercise performance and simultaneously minimizes lymphocyte dysfunction caused by oxidative stress has not yet been established. This study elucidates how various exercises regimens with/without hypoxia affect lymphocyte apoptosis induced by oxidative stress. METHODS: A total of 60 sedentary males were randomly divided into five groups. Each group (n = 12) received one of the five interventions: hypoxic-absolute exercise (HAT, 50%W max under 15%O2), hypoxic-relative exercise (HRT, 50% heart rate reserve under 15%O2), normoxic exercise (NT, 50%W max under 21%O2), hypoxic control (HC, resting under 15%O2), or normoxic control (NC, resting under 21%O2) for 30 min/day, 5 days/week for 4 weeks. RESULTS: Before the intervention, the graded exercise test (GXT, progressive exercise up to VO2max) decreased the surface thiol level on lymphocytes and subsequently augmented the extents of H2O2-induced mitochondria transmembrane potential (MTP) diminishing, caspase 3/8/9 activations, and phosphotidyl serine (PS) exposure in lymphocytes. However, 4 weeks of NT, HRT, or HAT reduced the extents of surface thiol decreasing on lymphocytes and H2O2-induced MTP diminishing, caspase 3/8/9 activations, and PS exposure in lymphocytes following GXT. Moreover, the HAT group exhibited greater improvements in pulmonary ventilation and VO2max than either NT or HRT group did. CONCLUSIONS: Exercise training with/without hypoxic exposure effectively alleviates lymphocyte apoptosis induced by oxidative stress following strenuous exercise. However, the HAT is superior to the NT or HRT for enhancing aerobic capacity.

Characteristics of CTX-M Extended-Spectrum ß-Lactamase-Producing Escherichia coli Strains Isolated from Multiple Rivers in Southern Taiwan.

Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli sequence type ST131 has emerged as the leading cause of community-acquired urinary tract infections and bacteremia worldwide. Whether environmental water is a potential reservoir of these strains remains unclear. River water samples were collected from 40 stations in southern Taiwan from February to August 2014. PCR assay and multilocus sequence typing (MLST) analysis were conducted to determine the CTX-M group and sequence type, respectively. In addition, we identified the seasonal frequency of ESBL-producing E. coli strains and their geographical relationship with runoffs from livestock and poultry farms between February and August 2014. ESBL-producing E. coli accounted for 30% of the 621 E. coli strains isolated from river water in southern Taiwan. ESBL-producing E. coli ST131 was not detected among the isolates. The most commonly detected strain was E. coli CTX-M group 9. Among the 92 isolates selected for MLST analysis, the most common ESBL-producing clonal complexes were ST10 and ST58. The proportion of ESBL-producing E. coli was significantly higher in areas with a lower river pollution index (P = 0.025) and regions with a large number of chickens being raised (P = 0.013). ESBL-producing E. coli strains were commonly isolated from river waters in southern Taiwan. The most commonly isolated ESBL-producing clonal complexes were ST10 and ST58, which were geographically related to chicken farms. ESBL-producing E. coli ST131, the major clone causing community-acquired infections in Taiwan and worldwide, was not detected in river waters.

Urinary tract infection in infants caused by extended-spectrum beta-lactamase-producing Escherichia coli: comparison between urban and rural hospitals.

BACKGROUND: Community-acquired urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli is an emerging problem. Compared with urban infants, rural infants may encounter different distributions of community-acquired resistant strains and various barriers to efficient management. METHODS: A retrospective survey and comparison was conducted for infants with UTI caused by ESBL-producing E. coli admitted to an urban hospital (n = 111) and a rural hospital (n = 48) in southern Taiwan from 2009 to 2012. RESULTS: Compared with 2009 and 2010, the total number of cases at both hospitals significantly increased in 2011 and 2012 (p < 0.001). Compared with the rural patients, the urban patients were significantly younger, and they had fewer days of fever before and after admission, fewer presentations of poor activity and poor appetite, and a lower serum creatinine level. Most of the patients had no prior history of illness, and we could not identify any significant different risk factors for acquiring ESBL-producing E. coli, such as past antimicrobial use, hospitalization, UTI, and underlying renal diseases, between the urban and rural populations. CONCLUSIONS: The increase in community-acquired UTI in infants caused by ESBL-producing E. coli was similar between the urban and rural populations. Our preliminary data suggest that the rural-urban disparities were probably related to easy access to health care by the urban population. ESBL complicates disease management, and the increase in the prevalence of ESBL producers is a major health concern and requires further healthy carrier and environmental surveillance.

Effect of thermal annealing on the surface properties of electrospun polymer fibers.

Electrospun polymer fibers are gaining importance because of their unique properties and applications in areas such as drug delivery, catalysis, or tissue engineering. Most studies to control the morphology and properties of electrospun polymer fibers focus on changing the electrospinning conditions. The effects of post-treatment processes on the morphology and properties of electrospun polymer fibers, however, are little studied. Here, the effect of thermal annealing on the surface properties of electrospun polymer fibers is investigated. Poly(methyl methacrylate) and polystyrene fibers are fist prepared by electrospinning, followed by thermal annealing processes. Upon thermal annealing, the surface roughness of the electrospun polymer fibers decreases. The driving force of the smoothing process is the minimization of the interfacial energy between polymer fibers and air. The water contact angles of the annealed polymer fibers also decrease with the annealing time.

[Photoinduced intra-molecular energy transfer of a novel phthalocyanine zinc(II) bearing poly (aryl benzyl ether) dendritic substitutents with carboxylic terminal].

The photoinduced intra-molecular energy transfer in phthalocyanine zinc(II) bearing poly (aryl benzyl ether) dendritic substituents with carboxylic terminal was studied by steady-state, time-resolved fluorescence and UV/Vis spectroscopic methods. The result shows that the complexes mainly existed as monomers in dimethyl sulfoxide. The light-harvesting ability of this series of dendritic phthalocyanines increased with the dendron generation under 270 nm. The effects of the dendron generation on the fluorescence characteristics of phthalocyanine cores was significantly, and the fluorescence lifetime and fluorescent quantum yield decreased with the increase of the dendron generation. Intra-molecular energy could be transferred from peripheral dendron acting as an energy hydrazine to the phthalocyanine core during a photo-induced process. With the dendrimer increasing, the intra-molecular energy transfer quantum yield increased. These results obviously indicated that this series of dendritic phthalocyanines is a king of novel compound with light-harvesting structure.

Investigating the therapeutic effects of novel compounds targeting inflammatory IL-1ß and IL-6 signaling pathways in spinocerebellar ataxia type 3.

At least seven dominantly inherited spinocerebellar ataxias (SCA) are caused by expansions of polyglutamine (polyQ)-encoding CAG repeat. The misfolded and aggregated polyQ-expanded proteins increase reactive oxygen species (ROS), cellular toxicity, and neuroinflammation in the disease pathogenesis. In this study, we evaluated the anti-inflammatory potentials of coumarin derivatives LM-021, LMDS-1, LMDS-2, and pharmacological chaperone tafamidis using mouse BV-2 microglia and SCA3 ataxin-3 (ATXN3)/Q75-GFP SH-SY5Y cells. The four tested compounds displayed anti-inflammatory activity by suppressing nitric oxide (NO), interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α production, and CD68 antigen (CD68) and histocompatibility-2 (MHCII) expression in lipopolysaccharides (LPS)/interferon (IFN)-γ-stimulated BV-2 microglia. In retinoic acid-differentiated ATXN3/Q75-GFP-expressing SH-SY5Y cells inflamed with LPS/IFN-γ-primed BV-2 conditioned medium, treatment with test compounds mitigated the increased caspase 1 activity and lactate dehydrogenase release, reduced ROS and ATXN3/Q75 aggregation, and promoted neurite outgrowth. Examination of IL-1ß and IL-6-mediated signaling pathways revealed that LM-021, LMDS-1, LMDS-2, and tafamidis decreased NLR family pyrin domain containing 1 (NLRP1), c-Jun N-terminal kinase/c-Jun proto-oncogene (JNK/JUN), inhibitor of kappa B (IκBα)/P65, mitogen-activated protein kinase 14/signal transducer and activator of transcription 1 (P38/STAT1), and/or Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling. The study results suggest the potential of LM-021, LMDS-1, LMDS-2, and tafamidis in treating SCA3 and probable other polyQ diseases.

[An improved paraffin embedding method for small core needle biopsy: technical introduction and evaluation].

PURPOSE: Modified agar pre-embedded paraffin embedding method was proposed to evaluate the effects on tissue integrity, histological morphology, protein and DNA detection in small specimens of core needle biopsies. METHODS: The core needle biopsy specimens of 10 patients with oral mucosal squamous cell carcinoma were subjected to modified agar pre-embedded paraffin embedding using molded embedding molds and conventional paraffin embedding respectively, the dehydration time of the former was 3.5 h and that of the latter was 12 h. After tissue treatment, H-E staining, histological morphology, immunohistochemistry (IHC), and DNA fluorescence in situ hybridization (FISH) were performed, respectively. The results were compared and analyzed using GraphPad Prism 9 software package. RESULTS: The modified agar pre-embedding method was less difficult to perform than the agar pre-embedding method, and easier to be promoted. Compared with conventional paraffin embedding method, the tissue dehydration time was significantly reduced(P＜0.001), and the results of microscopic histological morphology and subsequent IHC and FISH assays were reliable. CONCLUSIONS: The modified agar pre-embedded paraffin embedding method meets the requirements of clinical pathological diagnosis for tissue processing, and is worthy of clinical application for core needle biopsy specimens.

Coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 targeting inflammation and oxidative stress to protect BE(2)-M17 cells against α-synuclein toxicity.

Parkinson's disease (PD) is featured mainly by the loss of dopaminergic neurons and the presence of α-synuclein-containing aggregates in the substantia nigra of brain. The α-synuclein fibrils and aggregates lead to increased oxidative stress and neural toxicity in PD. Chronic inflammation mediated by microglia is one of the hallmarks of PD pathophysiology. In this report, we showed that coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 reduced the expression of major histocompatibility complex-II, NLR family pyrin domain containing (NLRP) 3, caspase-1, inducible nitric oxide synthase, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in α-synuclein-activated mouse BV-2 microglia. Release of pro-inflammatory mediators including nitric oxide, IL-1ß, IL-6 and TNF-α was also mitigated. In BE(2)-M17 cells expressing A53T α-synuclein aggregates, LM-021 and NC009-1 reduced α-synuclein aggregation, neuroinflammation, oxidative stress and apoptosis, and promoted neurite outgrowth. These protective effects were mediated by downregulating NLRP1, IL-1ß and IL-6, and their downstream pathways including nuclear factor (NF)-κB inhibitor alpha (IκBα)/NF-κB P65 subunit (P65), c-Jun N-terminal kinase (JNK)/proto-oncogene c-Jun (JUN), mitogen-activated protein kinase 14 (P38)/signal transducer and activator of transcription (STAT) 1, and Janus kinase 2 (JAK2)/STAT3. The study results indicate LM-021 and NC009-1 as potential new drug candidates for PD.

Geographic distribution of the major clone of extended-spectrum beta-lactamase-producing Escherichia coli infection in a pediatric community in southern Taiwan.

BACKGROUND: The geographic distribution of the major clone of sequence type 131 (ST131) in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) infections is not known. We analyzed the clinical features, resistance mechanisms, and geographic distribution of ESBL-producing E. coli clones in 120 children. METHODS: We studied the 120 ESBL-producing E. coli strains from children younger than 18 years. A VITEK 2 automated system was used to determine bacterial identification and ESBL production. Sequence type was determined by multi-locus sequence typing (MLST). The genetic relationship of the ESBL-producing strains was studied using pulsed-field gel electrophoresis (PFGE). Phylogenetic group and blaCTX-M group was performed using polymerase chain reaction (PCR). Multiplex PCR for detecting the common group 9 variant, CTX-M-14, and group 1 variant, CTX-M-15, was also performed. The addresses of the 120 children were collected, and plotted on the Taiwan map. RESULTS: The groups in the center of Kaohsiung City lived mainly in urban areas with a population density of over 10,000 people per square kilometer, and the majority of the Kaohsiung groups on the outskirts of the city center lived in suburban areas with a population density of under 6000 people per square kilometer. There was no statistically significant difference between the city center and outskirt groups in terms of clinical presentation, laboratory, and imaging data. However, more ST131 clones, major pulsotype groups, and phylogenetic group B2 strains were found in the center of Kaohsiung than on the outskirts. CONCLUSION: ESBL-producing E. coli clones may be more challenging to treat clinically. Most infections were community-acquired, and there appeared to be major pulsotype clones, mainly in urban areas. This reinforces the necessity of environmental surveillance and sanitary procedures for ESBL-producing E. coli.

Annealing effect on electrospun polymer fibers and their transformation into polymer microspheres.

Electrospinning is a simple and convenient technique to produce polymer fibers with diameters ranging from several nanometers to a few micrometers. Different types of polymer fibers have been prepared by electrospinning for various applications. Among different post-treatment methods of electrospun polymer fibers, the annealing process plays a critical role in controlling the fiber properties. The morphology changes of electrospun polymer fibers under annealing, however, have been little studied. Here we investigate the annealing effect of electrospun poly(methyl methacrylate) (PMMA) fibers and their transformation into PMMA microspheres. PMMA fibers with an average size of 2.39 µm are first prepared by electrospinning a 35 wt% PMMA solution in dimethylformamide. After the electrospun fibers are thermally annealed in ethylene glycol, a non-solvent for PMMA, the surfaces of the fibers undulate and transform into microspheres driven by the Rayleigh instability. The driving force of the transformation process is the minimization of the interfacial energy between the polymer fibers and ethylene glycol. The sizes of the microspheres fit well with the theoretical predictions. Longer annealing times are found to be required at lower temperatures to obtain the microspheres.

A new triarylindanone and a new isobenzofuranone derivative from Selaginella tamariscina.

A new triarylindanone, namely selagindanone A (1), and a new isobenzofuranone (2), 3,4-bis(4-hydroxyphenyl)isobenzofuran-1(3H)-one, were isolated from Selaginella tamariscina. Their structures were elucidated by comprehensive spectroscopic and mass spectrometric analyses, including 1 D-, 2 D-NMR and HR-ESI-MS. Compound 1 possesses a unique structural feature of triaryl-substituted in the skeleton of 1-indanone. In addition, compound 2 showed weak cytotoxicity against human hepatocellular carcinoma SMMC-7721 and HepG2 cell lines.

Hypoxic exercise training reduces senescent T-lymphocyte subsets in blood.

The integration and control of systemic immune responses depends on the regulated trafficking of T-lymphocytes. This study elucidates how various exercises regimens with/without hypoxia affect phenotypic characteristics of T-lymphocyte subsets in blood. Fifty sedentary males were randomly divided into five groups. Each group (n=10) received one of five interventions: normoxic (21%O2) resting (N-C), hypoxic (15%O2) resting (H-C), normoxic exercise (50%W(max) under 21%O2, N-T), hypoxic-relative exercise (50% maximal heart rate reserve under 15%O2, H-RT), or hypoxic-absolute exercise (50%W(max) under 15%O2, H-AT) for 30 min/day, 5 days/week for 4 weeks. Before the intervention, strenuous exercise up to exhaustion increased the mobilization of CD3, CD4, CD8, or CD8(bright) lymphocytes expressing activated (CD11a) or senescent (KLRG1) molecules into the peripheral blood compartment. The H-AT for 4 weeks up-regulated co-stimulatory molecule CD28 expression and was accompanied by depressed KLRG1 level on CD3, CD4, CD8, or CD8(bright) lymphocytes at rest or following exercise. Simultaneously, this intervention increased interferon-γ (IFN-γ) level and unchanged interleukin-4 level, as well as, decreased myeloperoxidase (MPO) and interleukin-6 levels in plasma. However, no significant changes in resting and exercise-induced mobilizations of various T-lymphocyte subsets and productions of cytokines and MPO occurred following the N-C, H-C, N-T, and H-RT interventions. Therefore, we conclude that 4-week H-AT intervention reduced senescent T-lymphocyte subsets with increasing IFN-γ level in blood, which responses are accompanied by depressed oxidative stress and pro-inflammatory cytokine production. These findings can help to determine an effective hypoxic exercise regimen to minimize immune dysfunction by retarding T-lymphocyte senescence.

Risk Factors and Prevalence of mcr-1-Positive Escherichia coli in Fecal Carriages Among Community Children in Southern Taiwan.

Colistin is the last resort antimicrobial for treating multidrug-resistant gram-negative bacterial infections. The plasmid-mediated colistin resistance gene, mcr-1, crucially influences colistin's resistance transmission. Human fecal carriages of mcr-1-positive Escherichia coli (E. coli) were detected in many regions worldwide; however, only a few studies have focused on children. Therefore, we identified the prevalence and risk factors of mcr-1-positive E. coli in fecal carriages among community children in Southern Taiwan. In this study, 510 stool samples were collected from April 2016 to August 2019 from the pediatric department at a medical center in Southern Taiwan. These samples were collected within 3 days after admission and were all screened for the presence of the mcr-1 gene. Diet habits, travel history, pet contact, and medical history were also obtained from participants to analyze the risk factors of their fecal carriages to mcr-1-positive E. coli. Antimicrobial susceptibility testing was determined using the VITEK 2 system and the broth microdilution test. Twelve mcr-1-positive E. coli. were isolated from 2.4% of the fecal samples. Through multivariate analysis, frequent chicken consumption (at least 3 times per week) had a significantly positive association with the presence of mcr-1-positive E. coli in fecal carriages (adjust odds ratio 6.60, 95% confidence interval1.58- 27.62, p = 0.033). Additionally, multidrug resistance was more common in mcr-1-positive E. coli. (75.0% vs. 39.5%, p = 0.031) than in non-mcr-1-positive Escherichia coli. Furthermore, the percentage of extraintestinal pathogenic E. coli in mcr-1-positive isolates was 83.3%. Some multi-locus sequence types in our mcr-1-positive E. coli were also similar to those isolated from food animals in the literature. The prevalence of fecal carriages of mcr-1-positive E. coli was low among community children in Southern Taiwan. Our data shows that chicken consumption with a higher frequency increases the risk of mcr-1-positive E. coli. in fecal carriages.