Topology, dynamics, and control of a muscle-architected soft arm.

Muscular hydrostats, such as octopus arms or elephant trunks, lack bones entirely, endowing them with exceptional dexterity and reconfigurability. Key to their unmatched ability to control nearly infinite degrees of freedom is the architecture into which muscle fibers are weaved. Their arrangement is, effectively, the instantiation of a sophisticated mechanical program that mediates, and likely facilitates, the control and realization of complex, dynamic morphological reconfigurations. Here, by combining medical imaging, biomechanical data, live behavioral experiments, and numerical simulations, an octopus-inspired arm made of [Formula: see text]200 continuous muscle groups is synthesized, exposing "mechanically intelligent" design and control principles broadly pertinent to dynamics and robotics. Such principles are mathematically understood in terms of storage, transport, and conversion of topological quantities, effected into complex 3D motions via simple muscle activation templates. These are in turn composed into higher-level control strategies that, compounded by the arm's compliance, are demonstrated across challenging manipulation tasks, revealing surprising simplicity and robustness.

Discovery of a dual-action small molecule that improves neuropathological features of Alzheimer's disease mice.

Alzheimer's disease (AD) is characterized by complex, multifactorial neuropathology, suggesting that small molecules targeting multiple neuropathological factors are likely required to successfully impact clinical progression. Acid sphingomyelinase (ASM) activation has been recognized as an important contributor to these neuropathological features in AD, leading to the concept of using ASM inhibitors for the treatment of this disorder. Here we report the identification of KARI 201, a direct ASM inhibitor evaluated for AD treatment. KARI 201 exhibits highly selective inhibition effects on ASM, with excellent pharmacokinetic properties, especially with regard to brain distribution. Unexpectedly, we found another role of KARI 201 as a ghrelin receptor agonist, which also has therapeutic potential for AD treatment. This dual role of KARI 201 in neurons efficiently rescued neuropathological features in AD mice, including amyloid beta deposition, autophagy dysfunction, neuroinflammation, synaptic loss, and decreased hippocampal neurogenesis and synaptic plasticity, leading to an improvement in memory function. Our data highlight the possibility of potential clinical application of KARI 201 as an innovative and multifaceted drug for AD treatment.

ALK5/VEGFR2 dual inhibitor TU2218 alone or in combination with immune checkpoint inhibitors enhances immune-mediated antitumor effects.

Transforming growth factor ß (TGFß) is present in blood of patients who do not respond to anti-programmed cell death (ligand) 1 [PD-(L)1] treatment, and through synergy with vascular endothelial growth factor (VEGF), it helps to create an environment that promotes tumor immune evasion and immune tolerance. Therefore, simultaneous inhibition of TGFß/VEGF is more effective than targeting TGFß alone. In this study, the dual inhibitory mechanism of TU2218 was identified through in vitro analysis mimicking the tumor microenvironment, and its antitumor effects were analyzed using mouse syngeneic tumor models. TU2218 directly restored the activity of damaged cytotoxic T lymphocytes (CTLs) and natural killer cells inhibited by TGFß and suppressed the activity and viability of regulatory T cells. The inactivation of endothelial cells induced by VEGF stimulation was completely ameliorated by TU2218, an effect not observed with vactosertib, which inhibits only TGFß signaling. The combination of TU2218 and anti-PD1 therapy had a significantly greater antitumor effect than either drug alone in the poorly immunogenic B16F10 syngeneic tumor model. The mechanism of tumor reduction was confirmed by flow cytometry, which showed upregulated VCAM-1 expression in vascular cells and increased influx of CD8 + CTLs into the tumor. As another strategy, combination of anti-CTLA4 therapy and TU2218 resulted in high complete regression (CR) rates in CT26 and WEHI-164 tumor models. In particular, immunological memory generated by the combination of anti-CTLA4 and TU2218 in the CT26 model prevented the development of tumors after additional tumor cell transplantation, suggesting that the TU2218-based combination has therapeutic potential in immunotherapy.

Progranulin haploinsufficiency mediates cytoplasmic TDP-43 aggregation with lysosomal abnormalities in human microglia.

BACKGROUND: Progranulin (PGRN) haploinsufficiency due to progranulin gene (GRN) variants can cause frontotemporal dementia (FTD) with aberrant TAR DNA-binding protein 43 (TDP-43) accumulation. Despite microglial burden with TDP-43-related pathophysiology, direct microglial TDP-43 pathology has not been clarified yet, only emphasized in neuronal pathology. Thus, the objective of this study was to investigate TDP-43 pathology in microglia of patients with PGRN haploinsufficiency. METHODS: To design a human microglial cell model with PGRN haploinsufficiency, monocyte-derived microglia (iMGs) were generated from FTD-GRN patients carrying pathogenic or likely pathogenic variants (p.M1? and p.W147*) and three healthy controls. RESULTS: iMGs from FTD-GRN patients with PGRN deficiency exhibited severe neuroinflammation phenotype and failure to maintain their homeostatic molecular signatures, along with impaired phagocytosis. In FTD-GRN patients-derived iMGs, significant cytoplasmic TDP-43 aggregation and accumulation of lipid droplets with profound lysosomal abnormalities were observed. These pathomechanisms were mediated by complement C1q activation and upregulation of pro-inflammatory cytokines. CONCLUSIONS: Our study provides considerable cellular and molecular evidence that loss-of-function variants of GRN in human microglia can cause microglial dysfunction with abnormal TDP-43 aggregation induced by inflammatory milieu as well as the impaired lysosome. Elucidating the role of microglial TDP-43 pathology in intensifying neuroinflammation in individuals with FTD due to PGRN deficiency and examining consequential effects on microglial dysfunction might yield novel insights into the mechanisms underlying FTD and neurodegenerative disorders.

Clinical feature, GALC variant spectrum, and genotype-phenotype correlation in Korean Krabbe disease patients: Multicenter experience over 13 years.

Krabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by deficiency of the galactocerebrosidase (GALC) due to variants in the GALC gene. Here, we provide the first and the largest comprehensive analysis of clinical and genetic characteristics, and genotype-phenotype correlations of KD in Korean in comparison with other ethnic groups. From June 2010 to June 2023, 10 patients were diagnosed with KD through sequencing of GALC. Clinical features, and results of GALC sequencing, biochemical test, neuroimaging, and neurophysiologic test were obtained from medical records. An additional nine previously reported Korean KD patients were included for review. In Korean KD patients, the median age of onset was 2 years (3 months-34 years) and the most common phenotype was adult-onset (33%, 6/18) KD, followed by infantile KD (28%, 5/18). The most frequent variants were c.683_694delinsCTC (23%) and c.1901T>C (23%), while the 30-kb deletion was absent. Having two heterozygous pathogenic missense variants was associated with later-onset phenotype. Clinical features were similar to those of other ethnic groups. In Korean KD patients, the most common phenotype was the adult-onset type and the GALC variant spectrum was different from that of the Caucasian population. This study would further our understanding of KD.

Hierarchically Micro- and Nanostructured Polymer via Crystallinity Alteration for Sustainable Environmental Cooling.

Cooling environments are a pervasive need in our society, with conventional air conditioners being the most popular approach. However, air conditioners rely heavily on electricity and Freon, a chemical that depletes ozone and contributes to greenhouse gas effects. To address this issue, passive daytime radiative coolers (PDRCs) have been proposed to achieve cooling by simultaneously reflecting sunlight and allowing internal heat to escape without electricity. Despite their potential, most high-performance PDRCs are composed of thick polymer films, which increases material costs during PDRC preparation and limits thermal transport. In this work, we introduced an economical and scalable solvent evaporation-based method to prepare a relatively thin hierarchically micro- and nanostructured poly(vinylidene fluoride-trifluoroethylene) via crystallinity alteration. Particularly, we find that the key to generating nanosized pores is to remove the water residual within the film without sample annealing, which significantly enhances the scattering efficiency across the solar spectrum. With our design, we demonstrate effective cooling of the outdoor environment, achieving a cooling temperature of Δ2.5 °C, with a film thickness of only 215 µm. Furthermore, our model suggested that applying this material could lead to annual energy savings of up to ∼39% in warmer climates across the country and up to 715 GJ nationwide. Developing effective PDRCs with reduced material thickness, such as the one discussed here, is imperative for implementing sustainable cooling solutions and reducing our carbon footprint.

Surgical necrotizing enterocolitis risk factors in extremely preterm infants: a Korean nationwide cohort study.

BACKGROUND: The incidence of necrotizing enterocolitis (NEC) is significantly associated with gestational age (GA). This study aimed to investigate risk factors for surgically treated NEC (sNEC) in extremely preterm infants (EPIs) using nationwide cohort registry. METHODS: Data were collected from 16,338 very-low-birth-weight infants registered in the Korean neonatal network. Clinical data of 5310 EPIs were retrospectively analyzed. sNEC was defined as infants with diagnosis of NEC requiring surgical treatment, who underwent surgical intervention for NEC or died before surgery. Infants were categorized into three groups based on their NEC status: infants without NEC (control), medically treated NEC (mNEC), and sNEC. These groups were matched based on GA to investigate risk factors for NEC. RESULTS: In EPIs, small for gestational age (SGA; odds ratio 1.68, 95% confidence interval [CI], 1.17-2.36, p = 0.004), hypotension (1.49, 1.18-1.89, p = 0.001), and IVH (1.63, 1.30-2.05, p < 0.001) were identified as risk factors for sNEC. Complete administration of antenatal steroid reduced the risk of sNEC (0.80, 0.64-0.99, p = 0.044). CONCLUSION: Our study demonstrated that EPIs who are SGA, and experience hypotension and IVH may be at an increased risk of developing NEC requiring surgery. These groups require close attention and monitoring for any signs of surgical indications of NEC. IMPACT: This nationwide cohort study aimed to identify characteristics of infants with necrotizing enterocolitis (NEC) among extremely preterm infants (EPIs) and analyze the risk factors associated with NEC requiring surgical intervention. Small for gestational age (SGA), hypotension, and intraventricular hemorrhage (IVH) were identified as significant risk factors for surgically treated NEC (sNEC) in EPIs. The administration of antenatal steroids decreases the risk of sNEC. Close attention and monitoring for EPIs with early identifiable risk factors such as SGA, hypotension, and IVH should be considered to prevent and detect sNEC early, ultimately leading to improved long-term outcomes.

Genomic and Metabolomic Analyses of Nocardiopsis maritima YSL2 as the Mycorrhizosphere Bacterium of Suaeda maritima (L.) Dumort.

Nine bacteria were isolated from the episphere of Suaeda maritima (L.) Dumort. Among them, the bacterial strain YSL2 displayed the highest antimicrobial activity on agar plates and exhibited significant novelty compared with other bacteria based on 16S rRNA analysis. Consequently, Nocardiopsis maritima YSL2T was subjected to phenotypic characterization and whole-genome sequencing. Phylogenetic analysis revealed its close association with Nocardiopsis aegyptia SNG49T. Furthermore, genomic analysis of strain YSL2T revealed the presence of various gene clusters, indicating its potential for producing antimicrobial secondary metabolites. Upon cultivation on a large scale, maritiamides A and B (1 and 2) were isolated and characterized as cyclic hexapeptides based on nuclear magnetic resonance, ultraviolet, infrared, and mass spectrometric data. The absolute configurations of the amino acid residues in the maritiamides were determined through chiral derivatization, utilizing FDAA and GITC. Maritiamides 1 and 2 exhibited promising antibacterial activities against Staphylococcus epidermidis and weakly inhibited the growth of Escherichia coli and Pseudomonas fluorescens.

Veillonella faecalis sp. nov., a propionic acid-producing bacterium isolated from the faeces of an infant.

A strictly anaerobic, Gram-stain-negative, catalase-negative, cocci-shaped, and propionate-producing bacterial strain, named Ds1651T was isolated from the fecal sample collected from a South Korean infant. Through a comparison of 16S rRNA gene sequences, it was revealed that Ds1651T had the highest phylogenetic affinity with Veillonella nakazawae KCTC 25297 T (99.86%), followed by Veillonella infantium KCTC 25370 T (99.80%), and Veillonella dispar KCTC 25309 T (99.73%) in the family Veillonellaceae. Average nucleotide identity values between Ds1651T and three reference species were 95.48% for Veillonella nakazawae KCTC 25297 T, 94.46% for Veillonella infantium KCTC 25370 T, and 92.81% for Veillonella dispar KCTC 25309 T. The G + C content of Ds1651T was 38.58 mol%. Major fermentation end-products were acetic and propionic acids in Trypticase peptone glucose yeast extract broth with 1% (v/v) sodium lactate. The predominant cellular fatty acids that account for more than 10% were summed in Feature 8 (C17:1 ω8c and/or C17:2) and C13:0. Based on the findings from phylogenetic, genomic, phenotypic, and chemotaxonomic studies, we propose that the type strain Ds1651T (= KCTC 25477 T = GDMCC 1.3707 T) represents a novel bacterial species within the genus Veillonella, with the proposed name Veillonella faecalis sp. nov.

Machine learning-based analysis for prediction of surgical necrotizing enterocolitis in very low birth weight infants using perinatal factors: a nationwide cohort study.

Early prediction of surgical necrotizing enterocolitis (sNEC) in preterm infants is important. However, owing to the complexity of the disease, identifying infants with NEC at a high risk for surgical intervention is difficult. We developed a machine learning (ML) algorithm to predict sNEC using perinatal factors obtained from the national cohort registry of very low birth weight (VLBW) infants. Data were collected from the medical records of 16,385 VLBW infants registered in the Korean Neonatal Network (KNN). Infants who underwent surgical intervention were identified with sNEC, and infants who received medical treatment, with medical NEC (mNEC). We used 38 variables, including maternal, prenatal, and postnatal factors that were obtained within 1 week of birth, for training. A total of 1085 patients had NEC (654 with sNEC and 431 with mNEC). VLBW infants showed a higher incidence of sNEC at a lower gestational age (GA) (p < 0.001). Our proposed ensemble model showed an area under the receiver operating characteristic curve of 0.721 for sNEC prediction.    Conclusion: Proposed ensemble model may help predict which infants with NEC are likely to develop sNEC. Through early prediction and prompt intervention, prognosis of sNEC may be improved. What is Known: • Machine learning (ML)-based techniques have been employed in NEC research for prediction, diagnosis, and prognosis, with promising outcomes. • While most studies have utilized abdominal radiographs and clinical manifestations of NEC as data sources, and have demonstrated their usefulness, they may prove weak in terms of early prediction. What is New: • We analyzed the perinatal factors of VLBW infants acquired within 7 days of birth and used ML-based analysis to identify which infants with NEC are vulnerable to clinical deterioration and at high risk for surgical intervention using nationwide cohort data.

Dynamic interplay of reactive oxygen and nitrogen species (ROS and RNS) in plant resilience: unveiling the signaling pathways and metabolic responses to biotic and abiotic stresses.

KEY MESSAGE: Plants respond to environmental challenges by producing reactive species such as ROS and RNS, which play critical roles in signaling pathways that lead to adaptation and survival strategies. Understanding these pathways, as well as their detection methods and effects on plant development and metabolism, provides insight into increasing crop tolerance to combined stresses. Plants encounter various environmental stresses (abiotic and biotic) that affect plant growth and development. Plants sense biotic and abiotic stresses by producing different molecules, including reactive species, that act as signaling molecules and stimulate secondary messengers and subsequent gene transcription. Reactive oxygen and nitrogen species (ROS and RNS) are produced in both physiological and pathological conditions in the plasma membranes, chloroplasts, mitochondria, and endoplasmic reticulum. Various techniques, including spectroscopy, chromatography, and fluorescence methods, are used to detect highly reactive, short-half-life ROS and RNS either directly or indirectly. In this review, we highlight the roles of ROS and RNS in seed germination, root development, senescence, mineral nutrition, and post-harvest control. In addition, we provide information on the specialized metabolism involved in plant growth and development. Secondary metabolites, including alkaloids, flavonoids, and terpenoids, are produced in low concentrations in plants for signaling and metabolism. Strategies for improving crop performance under combined drought and pathogen stress conditions are discussed in this review.

Separation of Lipoproteins for Quantitative Analysis of 14C-Labeled Lipid-Soluble Compounds by Accelerator Mass Spectrometry.

To date, 14C tracer studies using accelerator mass spectrometry (AMS) have not yet resolved lipid-soluble analytes into individual lipoprotein density subclasses. The objective of this work was to develop a reliable method for lipoprotein separation and quantitative recovery for biokinetic modeling purposes. The novel method developed provides the means for use of small volumes (10-200 µL) of frozen plasma as a starting material for continuous isopycnic lipoprotein separation within a carbon- and pH-stable analyte matrix, which, following post-separation fraction clean up, created samples suitable for highly accurate 14C/12C isotope ratio determinations by AMS. Manual aspiration achieved 99.2 ± 0.41% recovery of [5-14CH3]-(2R, 4'R, 8'R)-α-tocopherol contained within 25 µL plasma recovered in triacylglycerol rich lipoproteins (TRL = Chylomicrons + VLDL), LDL, HDL, and infranatant (INF) from each of 10 different sampling times for one male and one female subject, n = 20 total samples. Small sample volumes of previously frozen plasma and high analyte recoveries make this an attractive method for AMS studies using newer, smaller footprint AMS equipment to develop genuine tracer analyses of lipophilic nutrients or compounds in all human age ranges.

Concurrent primary splenic lymphoma and mammary gland tumour with polycystic ovaries in a dog.

Here, we report a rare case of concurrent primary splenic lymphoma and mammary gland tumour (MGT) with polycystic ovaries in a 10-year-old, intact female Jindo dog. The dog was presented with multiple masses in the fourth left mammary gland, the largest of which measured 6 cm in diameter, along with enlargement of the left inguinal lymph node on physical examination. Ultrasonography, radiography, and computed tomography scans revealed polycystic ovaries and a mass in the tail of the spleen, after total splenectomy and mastectomy with ovariohysterectomy, histopathological examination identified splenic diffuse large B cell lymphoma and malignant myoepithelioma of the mammary gland was found. To our knowledge, this is the first report of the concurrent occurrence of splenic lymphoma, MGT, and polycystic ovaries in a dog.

Canine multiple primary tumours: Mammary tubular carcinoma, uterine leiomyosarcoma, and facial sebaceous epithelioma.

Multiple primary malignant tumours (MPMTs) are multiple neoplasms with independent pathogenetic origins, placing great importance on the tumorigenesis and clinical treatment. However, due to the rare occurrence and diagnostic confusion, MPMTs have rarely been investigated in veterinary medicine. In this report, a 10-year-old intact female Maltese dog had MPMTs, consisting of two malignant tumours and one benign tumour each derived from a topographically different site: tubular carcinoma in the mammary glands, leiomyosarcoma in the uterus and sebaceous epithelioma in the cheek. The unique combination of MPMTs would be the first case in veterinary research to give insight into the diagnosis, disease characteristics, and surgical treatment.

Early rituximab treatment reduces long-term disability in aquaporin-4 antibody-positive neuromyelitis optica spectrum.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) causes relapsing inflammatory attacks in the central nervous system, leading to disability. As rituximab, a B-lymphocyte-depleting monoclonal antibody, is an effective in preventing NMOSD relapses, we hypothesised that earlier initiation of rituximab can also reduce long-term disability of patients with NMOSD. METHODS: This multicentre retrospective study involving 19 South Korean referral centres included patients with NMOSD with aquaporin-4 antibodies receiving rituximab treatment. Factors associated with the long-term Expanded Disability Status Scale (EDSS) were assessed using multivariable regression analysis. RESULTS: In total, 145 patients with rituximab treatment (mean age of onset, 39.5 years; 88.3% female; 98.6% on immunosuppressants/oral steroids before rituximab treatment; mean disease duration of 121 months) were included. Multivariable analysis revealed that the EDSS at the last follow-up was associated with time to rituximab initiation (interval from first symptom onset to initiation of rituximab treatment). EDSS at the last follow-up was also associated with maximum EDSS before rituximab treatment. In subgroup analysis, the time to initiation of rituximab was associated with EDSS at last follow-up in patients aged less than 50 years, female and those with a maximum EDSS score ≥6 before rituximab treatment. CONCLUSIONS: Earlier initiation of rituximab treatment may prevent long-term disability worsening in patients with NMOSD, especially among those with early to middle-age onset, female sex and severe attacks.

Experimental Investigation of Cavitation Bulk Nanobubbles Characteristics: Effects of pH and Surface-Active Agents.

Nanobubbles (NBs) have a widespread application in antimicrobial activity, wastewater treatment, and ecological restoration due to numerous peculiar characteristics, such as small diameter, long-term stability, and ability to produce hydroxyl radicals. Despite significant applications, only limited comprehensive investigations are available on the role of surfactants and pH in NBs characteristics. Therefore, this study examines the effects of different surfactants (i.e., anionic, cationic, and nonionic) and pH medium on bulk NB formation, diameter, concentration, bubble size distribution (BSD), ζ-potential, and stability. The effect of surfactant at concentrations above and below the critical micelle concentration was investigated. NBs were generated in deionized (DI) water using a piezoelectric transducer. The stability of NBs was assessed by tracking the variation in diameter and concentration over time. In a neutral medium, the diameter of NBs is smaller than in other surfactant or pH mediums. The diameter, concentration, BSD, and stability of NBs are strongly influenced by the ζ-potential rather than the solution medium. BSD curve shifts to a smaller bubble diameter when the magnitude of ζ-potential is high in any solution. In pure water, surfactant, and pH mediums, NBs have existed for a long time. NBs have a shorter life span in environments with a pH ≤ 3. Surfactant adsorption on the surface of NBs increases with increasing surfactant concentration up to a certain limit, beyond which it declines substantially. The Derjaguin-Landau-Verwey-Overbeek (DLVO) theory was used to interpret the NBs stability, resulting in a total potential energy barrier that is positive and greater than 45.55 kBT for 6 ≤ pH ≤ 11, whereas for pH < 6, the potential energy barrier essentially vanishes. Moreover, an effort has also been made to explicate the plausible prospect of ion distribution and its alignment surrounding NBs in cationic and anionic surfactants. This study will extend the in-depth investigation of NBs for industrial applications involving NBs.

Biomarkers for predicting type 2-high and uncontrolled asthma in real-world practice.

BACKGROUND: Blood eosinophil count (BEC), immunoglobulin (Ig) E, and fractional exhaled nitric oxide (FeNO) are key clinical indicators for identifying type 2 (T2) asthma. OBJECTIVE: To provide optimal cutoff points of T2 markers for assessing T2-high or uncontrolled asthma in real-world practice. METHODS: Various clinical and laboratory parameters were analyzed according to the result of T2 markers (BEC, serum-free IgE, and FeNO) in adults with asthma who had maintained antiasthmatic medications. The cutoff levels for representing uncontrolled asthma were determined using receiver operating characteristic analysis. Blood levels of periostin and eosinophil-derived neurotoxin were measured by enzyme-linked immunosorbent assay. Activation markers of circulating eosinophils (Siglec8+) and neutrophils (CD66+) were analyzed by flow cytometry. RESULTS: Of 133 patients with asthma, 23 (17.3%) had 3 T2 markers (BEC ≥ 300 cells/µL, serum-free IgE ≥ 120 ng/mL, and FeNO ≥ 25 parts per billion) and significantly higher levels of sputum eosinophils, blood eosinophil-derived neurotoxin, and Siglec8+ eosinophils but lower 1-second forced expiratory volume percentage, in addition to a higher rate of uncontrolled status (P < .05 for all). Furthermore, patients with uncontrolled asthma had significantly higher levels of FeNO and BEC with lower 1-second forced expiratory volume percentage (P < .05 for all). The optimal cutoff values for predicting uncontrolled asthma were found to be 22 parts per billion of FeNO levels, 161.4 cells/L of BECs, and 85.9 ng/mL of serum-free IgE levels. CONCLUSION: We suggest the optimal cutoff values of BEC, IgE, and FeNO for classifying T2-high or uncontrolled asthma, which could be applied as candidate biomarkers for targeting patients with asthma who require T2 biologics.

Prevalence of motor neuron diseases in gout patients: a nationwide population-based cohort study.

BACKGROUND: Increased uric acid may have a protective effect in motor neuron diseases (MNDs). The association between gout, characterized by hyperuricemia, and MNDs was not investigated previously. To estimate the prevalence of MNDs in gout patients using the Health Insurance and Review Assessment (HIRA) database, a nationwide database of South Korea. METHODS: The current descriptive study was conducted using the HIRA database. Subjects diagnosed with gout from 2011 to 2018 were included in this study. Among them, the annual prevalence of MNDs was analyzed, stratified by age and sex. Comorbidities including the Charlson Comorbidity Index score and type of prescribed gout-related drug were also demonstrated. RESULTS: The age-adjusted prevalence of MNDs per 105 persons ranged from 0.598 (95% confidence interval (CI): - 0.231-1.426) to 2.534 (95% CI: 1.100-3.968) between 2011 and 2018. Compared to previous reports, the prevalence of MNDs, especially amyotrophic lateral sclerosis (ALS), in gout patients was significantly lower than in the general population. None of the female gout patients were diagnosed with MNDs. Cerebrovascular accidents, vascular risk factors including hypertension, dyslipidemia, and diabetic complications, and the use of uric acid-lowering agents were more common in gout patients with MNDs than in those without MNDs. CONCLUSION: This study adds to the evidence of MND prevalence in gout patients. Gout might have a protective effect against the risk of MNDs.

Xinghamide A, a New Cyclic Nonapeptide Found in Streptomyces xinghaiensis.

Xinghamide A (1), a new nonapeptide, was discovered in Streptomyces xinghaiensis isolated from a halophyte, Suaeda maritima (L.) Dumort. Based on high-resolution mass and NMR spectroscopic data, the planar structure of 1 was established, and, in particular, the sequence of nine amino acids was determined with ROESY and HMBC NMR spectra. The absolute configurations of the α-carbon of each amino acid residue were determined with 1-fluoro-2,4-dinitrophenyl-l-and -d-leucine amide (Marfey's reagents) and 2,3,4,6-tetra-O-acetyl-ß-d-glucopyranosyl isothiocyanate, followed by LC-MS analysis. The anti-inflammatory activity of xinghamide A (1) was evaluated by inhibitory abilities against the nitric oxide (NO) secretion and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

Chemical constituents from the stem bark of Albizia julibrissin and their SREBP-1c inhibitory activity.

One new lignan, julibrissinoside II, along with thirteen known compounds, was isolated from the stem bark of Albizia julibrissin. The structure of julibrissinoside II was determined on the basis of extensive spectroscopic methods, including NMR and CD spectroscopic data. The isolated compounds were tested for their SREBP-1c inhibitory activity at different concentrations using mouse hepatocyte AML12 cell lines. Among them, linoleic acid (2) and 3-O-methylfisetin (4) showed significant SREBP-1c inhibitory activity at the concentration of 100 µM.