A p21-ATD mouse model for monitoring and eliminating senescent cells and its application in liver regeneration post injury.

Cellular senescence associates with pathological aging and tissue dysfunctions. Studies utilizing mouse models for cell lineage tracings have emphasized the importance of senescence heterogeneity in different organs and cell types. Here, we constructed a p21- (Akaluc - tdTomato - Diphtheria Toxin Receptor [DTR]) (ATD) mouse model to specifically study the undefined mechanism for p21-expressing senescent cells in the aged and liver injury animals. The successful expressions of these genes enabled in vitro flow cytometric sorting, in vivo tracing, and elimination of p21-expressing senescent cells. During the natural aging process, p21-expressing cells were found in various tissues of p21-ATD mice. Eliminating p21-expressing cells in the aged p21-ATD mice recovered their multiple biological functions. p21-ATD/Fah-/- mice, bred from p21-ATD mice and fumarylacetoacetate hydrolase (Fah)-/- mice of liver injury, showed that the majority of their senescent hepatocytes were the phenotype of p21+ rather than p16+. Furthermore, eliminating the p21-expressing hepatocytes significantly promoted the engraftment of grafted hepatocytes and facilitated liver repopulation, resulting in significant recovery from liver injury. Our p21-ATD mouse model serves as an optimal model for studying the pattern and function of p21-expressing senescent cells under the physical and pathological conditions during aging.

Bleeding Risk of Cold Versus Hot Snare Polypectomy for Pedunculated Colorectal Polyps Measuring 10 mm or Less: Subgroup Analysis of a Large Randomized Controlled Trial.

INTRODUCTION: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions. METHODS: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp. RESULTS: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group. DISCUSSION: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm.

Microglia LILRB4 upregulation reduces brain damage after acute ischemic stroke by limiting CD8+ T cell recruitment.

BACKGROUND: Leukocyte immunoglobulin-like receptor B4 (LILRB4) plays a significant role in regulating immune responses. LILRB4 in microglia might influence the infiltration of peripheral T cells. However, whether and how LILRB4 expression aggravates brain damage after acute ischemic stroke remains unclear. This study investigates the role of LILRB4 in modulating the immune response and its potential protective effects against ischemic brain injury in mice. METHODS AND RESULTS: Microglia-specific LILRB4 conditional knockout (LILRB4-KO) and overexpression transgenic (LILRB4-TG) mice were constructed by a Cre-loxP system. Then, they were used to investigate the role of LILRB4 after ischemic stroke using a transient middle cerebral artery occlusion (tMCAO) mouse model. Spatial transcriptomics analysis revealed increased LILRB4 expression in the ischemic hemisphere. Single-cell RNA sequencing (scRNA-seq) identified microglia-cluster3, an ischemia-associated microglia subcluster with elevated LILRB4 expression in the ischemic brain. Flow cytometry and immunofluorescence staining showed increased CD8+ T cell infiltration into the brain in LILRB4-KO-tMCAO mice. Behavioral tests, cortical perfusion maps, and infarct size measurements indicated that LILRB4-KO-tMCAO mice had more severe functional deficits and larger infarct sizes compared to Control-tMCAO and LILRB4-TG-tMCAO mice. T cell migration assays demonstrated that LILRB4-KD microglia promoted CD8+ T cell recruitment and activation in vitro, which was mitigated by CCL2 inhibition and recombinant arginase-1 addition. The scRNA-seq and spatial transcriptomics identified CCL2 was predominantly secreted from activated microglia/macrophage and increased CCL2 expression in LILRB4-KD microglia, suggesting a chemokine-mediated mechanism of LILRB4. CONCLUSION: LILRB4 in microglia plays a crucial role in modulating the post-stroke immune response by regulating CD8+ T cell infiltration and activation. Knockout of LILRB4 exacerbates ischemic brain injury by promoting CD8+ T cell recruitment. Overexpression of LILRB4, conversely, offers neuroprotection. These findings highlight the therapeutic potential of targeting LILRB4 and its downstream pathways to mitigate immune-mediated damage in ischemic stroke.

Long-Term Sulfonylurea Use and Impaired Awareness of Hypoglycemia Among Patients With Type 2 Diabetes in Taiwan.

PURPOSE: We undertook a study to investigate the relationship between duration of medication use and prevalence of impaired awareness of hypoglycemia (IAH) among patients with insulin-treated or sulfonylurea-treated type 2 diabetes in Taiwan. METHODS: A total of 898 patients (41.0% insulin users, 65.1% sulfonylurea users; mean [SD] age = 59.9 [12.3] years, 50.7% female) were enrolled in pharmacies, clinics, and health bureaus of Tainan City, Taiwan. Presence of IAH was determined with Chinese versions of the Gold questionnaire (Gold-TW) and Clarke questionnaire (Clarke-TW). Sociodemographics, disease and treatment histories, diabetes-related medical care, and health status were collected. We used multiple logistic regression models to assess the relationship between duration of medication use and IAH. RESULTS: Overall IAH prevalence was 41.0% (Gold-TW) and 28.2% (Clarke-TW) among insulin users, and 65.3% (Gold-TW) and 51.3% (Clarke-TW) among sulfonylurea users. Prevalence increased with the duration of sulfonylurea use, whereas it decreased with the duration of insulin use. After controlling for potential confounders, 5 or more years of sulfonylurea use was significantly associated with 3.50-fold (95% CI, 2.39-5.13) and 3.06-fold (95% CI, 2.11-4.44) increases in the odds of IAH based on the Gold-TW and Clarke-TW criteria, respectively. On the other hand, regular blood glucose testing and retinal examinations were associated with reduced odds in both insulin users and sulfonylurea users. CONCLUSIONS: The prevalence of IAH was high among patients using sulfonylureas long term, but the odds of this complication were attenuated for those who received regular diabetes-related medical care. Our study suggests that long-term sulfonylurea use and irregular follow-up increase risk for IAH. Further prospective studies are needed to confirm the observed associations.Annals Early Access article.

Biodegradable microplastics reduce the effectiveness of biofertilizers by altering rhizospheric microecological functions.

The effectiveness of biofertilizers as a cost-effective crop yield enhancer can be compromised by residual soil pollutants. However, the impact of accumulated polyadipate/butylene terephthalate microplastics (PBAT-MPs) from biodegradable mulch films on biofertilizer application and the consequent growth of crop plants remains unclear. Here, the effects of different levels of PBAT-MPs in soil treated with Bacillus amyloliquefaciens biofertilizer were assessed in a four-week potted experiment. PBAT-MPs significantly decreased the growth-promoting effect of the biofertilizer on Brassica chinensis L., resulting in a notable reduction in both above- and belowground biomass (up to 52.91% and 57.53%, respectively), as well as nitrate and crude fiber contents (up to 12.18% and 13.64%, respectively). In the rhizosphere microenvironment, PBAT-MPs increased soil organic carbon by 2.63-fold and organic matter by 2.68-fold, while enhancing sucrase (from 67.55% to 108.89%) and cellulase (from 31.26% to 49.10%) activities. PBAT-MPs also altered the rhizospheric bacterial community composition/diversity, resulting in more complex microbial networks. With regard to microbial function, PBAT-MPs impacted carbon metabolic function by inhibiting the 3-hydroxypropionate/4-hydroxybutyrate fixation pathway and influencing chitin and lignin degradation processes. Overall, the rhizospheric microbial profiles (composition, function, and network interactions) were the main contributors to plant growth inhibition. This study provides a practical case and theoretical basis for rational use of biodegradable mulch films and indicates that the residue of biodegradable films needs pay attention.

Immobilized Tetraalkylammonium Cations Enable Metal-free CO2 Electroreduction in Acid and Pure Water.

Carbon dioxide reduction reaction (CO2 RR) provides an efficient pathway to convert CO2 into desirable products, yet its commercialization is greatly hindered by the huge energy cost due to CO2 loss and regeneration. Performing CO2 RR under acidic conditions containing alkali cations can potentially address the issue, but still causes (bi)carbonate deposition at high current densities, compromising product Faradaic efficiencies (FEs) in present-day acid-fed membrane electrode assemblies. Herein, we present a strategy using a positively charged polyelectrolyte-poly(diallyldimethylammonium) immobilized on graphene oxide via electrostatic interactions to displace alkali cations. This enables a FE of 85 %, a carbon efficiency of 93 %, and an energy efficiency (EE) of 35 % for CO at 100 mA cm-2 on modified Ag catalysts in acid. In a pure-water-fed reactor, we obtained a 78 % CO FE with a 30 % EE at 100 mA cm-2 at 40 °C. All the performance metrics are comparable to or even exceed those attained in the presence of alkali metal cations.

Effective Faraday rotator based on the TbYO3 crystal with a high Verdet constant and a high thermal conductivity.

Facing the demand of high-power laser development, a high-quality magneto-optical crystal with a high Verdet constant and a high thermal conductivity is needed. Herein, an effective Faraday rotation based on a TbYO3 single crystal with a strong magneto-optical effect, grown by the laser floating zone method, is demonstrated for the first time, to the best of our knowledge. The TbYO3 crystal has the Verdet constant which is 2.16 times (106 rad·m-1 T-1) higher than that of the TGG crystal (49 rad·m-1 T-1) at 880 nm. Additionally, the TbYO3 crystal also has a thermal conductivity of 11.8 W·m-1·K-1 and a laser-induced damage threshold of 1.59 GW·cm-2. These advantages can allow the TbYO3 crystal to be an attractive magneto-optical material.

Identifying self-reported health-related problems in home-based rehabilitation of older patients after hip replacement in China: a machine learning study based on Omaha system theory.

BACKGROUND: With the aging of the population, the number of total hip replacement surgeries is increasing globally. Hip replacement has undergone revolutionary advancements in surgical methods and materials. Due to the short length of hospitalization, rehabilitation care is mainly home-based. The needs and concerns about such home-based rehabilitation are constantly changing, requiring continuous attention. OBJECTIVE: To explore effective methods for comprehensively identifying older patients' self-reported outcomes after home-based rehabilitation for hip replacement, in order to develop appropriate intervention strategies for patient rehabilitation care in the future. METHODS: This study constructed a corpus of patients' self-reported rehabilitation care problems after hip replacement, based on the Omaha classification system. This study used the Python development language and implemented artificial intelligence to match the corpus data on the cooperation platform, to identify the main health-related problems reported by the patients, and to perform statistical analyses. RESULTS: Most patients had physical health-related problems. More than 80% of these problems were related to neuromusculoskeletal function, interpersonal relationships, pain, health care supervision, physical activity, vision, nutrition, and residential environment. The most common period in which patients' self-reported problems arose was 6 months post-surgery. The relevant labels that were moderately related to these problems were: Physiology-Speech and Language and Physiology-Mind (r = 0.45), Health-Related Behaviors-Nutrition and Health-Related Behaviors-Compliance with Doctors' Prescription (r = 0.40). CONCLUSION: Physiological issues remain the main health-related issues for home-based rehabilitation after hip replacement in older patients. Precision care has become an important principle of rehabilitation care. This study used a machine learning method to obtain the largest quantitative network data possible. The artificial intelligence capture was fully automated, which greatly improved efficiency, as compared to manual data entering.

Evaluation of chemotherapy and radiotherapy in the adjuvant management of uterine carcinosarcoma: a population-based analysis.

PURPOSE: To evaluate the effects of adjuvant chemotherapy (CT) and radiotherapy (RT) on the survival of uterine carcinosarcoma (UCS) patients. METHODS: We analyzed 3207 patients with uterine carcinosarcoma without distant metastasis after surgery from 2004 to 2015 by utilizing data from the Surveillance, Epidemiology, and End Results database. Generally, cancer-specific survival (CSS) and overall survival (OS) outcomes were analyzed by Kaplan-Meier and Cox proportional hazards regression models. Further subgroup survival analysis was performed for those receiving RT and chemoradiotherapy (CRT). RESULTS: In general, both univariate and multivariate analyses showed that age, race, marital status, stage, lymph node metastasis, lymphadenectomy (LND), RT, and chemotherapy (CT) were associated with improved CSS and OS (P < 0.05). Further subgroup analysis showed that CRT exhibited a survival advantage over RT or CT alone in different groups. Various RT modalities, including brachytherapy (BT), external radiotherapy (EBRT), and EBRT + BT, were correlated with improved survival for patients aged 60-69 years with stage III-IV disease and lymph node metastasis. Patients with stage I-II disease aged > 70 years seemed to gain survival benefits from brachytherapy (BT) alone. BT with or without external radiotherapy was associated with improved survival for those who did not undergo lymphadenectomy. CONCLUSION: For UCS without distant metastasis after surgery, CRT should be considered. Regarding RT, BT alone is efficient in improving survival, especially for patients with stage I-II disease aged > 70 years old. EBRT alone does not show results in survival improvement for patients who did not undergo LND and those with lymph node metastasis. However, considering the limitation of SEER database, further studies with more large sample size and strict study design are needed to confirm it.

Salivary Extracellular Vesicles: Biomarkers and Beyond in Human Diseases.

Extracellular vesicles, as bioactive molecules, have been extensively studied. There are abundant studies in the literature on their biogenesis, secretion, structure, and content, and their roles in pathophysiological processes. Extracellular vesicles have been reviewed as biomarkers for use in diagnostic tools. Saliva contains many extracellular vesicles, and compared with other body fluids, it is easier to obtain in a non-invasive way, making its acquisition more easily accepted by patients. In recent years, there have been numerous new studies investigating the role of salivary extracellular vesicles as biomarkers. These studies have significant implications for future clinical diagnosis. Therefore, in this paper, we summarize and review the potential applications of salivary extracellular vesicles as biomarkers, and we also describe their other functions (e.g., hemostasis, innate immune defense) in both oral and non-oral diseases.

Identification and functional study of AA11 family polysaccharide monooxygenase genes in filamentous fungus Podospora anserina.

The lytic polysaccharide monooxygenase (LPMO) in the auxiliary active protein family (AA family) catalyzes the oxidative depolymerization of various refractory carbohydrates including cellulose, chitin and starch. While accumulating studies investigate the enzymology of LPMO, the research on the inactivation of LPMO genes has been rarely explored. In this study, five LPMO genes PaLPMO11A (Pa_4_4790), PaLPMO11B (Pa_1_5310), PaLPMO11C (Pa_2_7840), PaLPMO11D (Pa_2_8610) and PaLPMO11E (Pa_3_9420) of the AA11 family in the filamentous fungus Podospora anserina were knocked out by homologous recombination. Single mutants ΔPaLPMO11A (ΔA), ΔPaLPMO11B (ΔB), ΔPaLPMO11C (ΔC), ΔPaLPMO11D (ΔD) and ΔPaLPMO11E (ΔE) were constructed, and then all polygenic mutants were constructed via genetic crosses. The differences in the growth rate and sexual reproduction between wild type and mutant strains were observed on different carbon source media. The alteration of oxidative stress and cellulose degradation ability were found on DAB and NBT staining and cellulase activity determination. These results implicated that LPMO11 genes play a key role in the growth, development, and lignocellulose degradation of P. anserina. The results showed that the spore germination efficiency, growth rate and reproductive capacity of mutant strains including ΔBΔCΔE, ΔAΔBΔCΔE, ΔAΔCΔDΔE and ΔAΔBΔCΔDΔE was significantly decreased on different cellulose carbon sources and the remaining strains have no difference. The reduced utilization of various carbon sources, the growth rate, the spore germination rate, the number of fruiting bodies, the normal fruiting bodies, the shortened life span and the ability to degrade cellulose were found in strains which all five genes in the PaLPMO11 family were deleted. However, the strain still had 45% cellulase activity compared to wild type. These results suggest that LPMO11 genes may be involved in the growth and development, sexual reproduction, senescence and cellulose degradation of P. anserina. This study provides information for systematically elucidating the regulatory mechanism of lignocellulose degradation in filamentous fungus P. anserina.

[A two-dimensional video based quantification method and clinical application research of motion disorders].

The increasing prevalence of the aging population, and inadequate and uneven distribution of medical resources, have led to a growing demand for telemedicine services. Gait disturbance is a primary symptom of neurological disorders such as Parkinson's disease (PD). This study proposed a novel approach for the quantitative assessment and analysis of gait disturbance from two-dimensional (2D) videos captured using smartphones. The approach used a convolutional pose machine to extract human body joints and a gait phase segmentation algorithm based on node motion characteristics to identify the gait phase. Moreover, it extracted features of the upper and lower limbs. A height ratio-based spatial feature extraction method was proposed that effectively captures spatial information. The proposed method underwent validation via error analysis, correction compensation, and accuracy verification using the motion capture system. Specifically, the proposed method achieved an extracted step length error of less than 3 cm. The proposed method underwent clinical validation, recruiting 64 patients with Parkinson's disease and 46 healthy controls of the same age group. Various gait indicators were statistically analyzed using three classic classification methods, with the random forest method achieving a classification accuracy of 91%. This method provides an objective, convenient, and intelligent solution for telemedicine focused on movement disorders in neurological diseases.

Research progress in role of exosomes exosomes in mental disorders. / å¤–æ³Œä½“åœ¨ç²¾ç¥žéšœç¢ä¸­ä½œç”¨çš„ç ”ç©¶è¿›å±•.

Exosomes are a class of extracellular vesicles with a structure of lipid bilayer-membrane. In the central nervous system (CNS), exosomes can be secreted from both neurons and glial cells. Exosomes released into the extracellular matrix can freely cross the blood-brain barrier and function as crucial carriers of cellular communication and substance exchange in the CNS. Exosomes play a key role in the pathological process of mental disorders such as schizophrenia, depression, and bipolar disorder, and they have the potential to be used as a targeted carrier of antipsychotic medications. Exosomes are likely to become a new tool in the future to aid in the early prevention, accurate diagnosis, and effective treatment for people with mental disorders.

Severe Acute Exacerbation After Cessation of Nucleos(t)ide Analog for Chronic Hepatitis B: A Real-World Study of Routine Practice.

There is an ongoing debate as to whether patients with chronic hepatitis B (CHB) may discontinue nucleos(t)ide analogue (NA) therapy before seroclearance of hepatitis B surface antigen (HBsAg).1 Whereas treatment discontinuation may facilitate HBsAg seroclearance and avoid indefinite drug exposure,2 reactivation of viral replication almost always follows treatment cessation and frequently leads to clinical flares.3 In patients who encounter withdrawal flares, severe acute exacerbation (SAE) could occur with fatal consequences.4 Quantitative knowledge about the risk of SAE is imperative to inform the debate and also the practice.

Overexpression of VPS11 antagonizes the promoting effect of miR-542-3p on Mycobacterium tuberculosis survival in macrophages by regulating autophagy.

Impaired autophagy is an important cause of Mycobacterium tuberculosis survival in macrophages. VPS11 is an important regulator of autophagy; decreased VPS11 expression has been observed in macrophages after tuberculosis (TB) infection. Gene ontology data revealed that various miRNAs (for example, miR-542-3p) were upregulated in macrophages upon TB infection; thus, these miRNAs were likely to reduce VPS11 expression. In this study, both TB patients and healthy subjects were enrolled, and the levels of VPS11 and some miRNAs in their blood macrophages were measured. Moreover, various macrophages were cultured and infected with M. tuberculosis. Luciferase reporter, RNA pulldown, and RNA immunoprecipitation assays were performed to determine the regulatory effect of miR-542-3p on VPS11 expression. Results showed that VPS11 expression was downregulated, whereas miR-542-3p expression was upregulated in blood macrophages after TB infection. TB infection reduced VPS11 levels in two human macrophages in vitro, but not in mouse macrophages. This might be because the seed sequence exists in the VPS11 3' untranslated region in humans, but is absent in mice and rats. miR-542-3p promoted M. tuberculosis survival in human macrophages, but VPS11 overexpression antagonized the promoting effect of miR-542-3p. Further, VPS11 was confirmed as a target of miR-542-3p. Overexpression of VPS11 or depletion of miR-542-3p promoted autophagy, which was suppressed upon TB infection. In summary, VPS11 overexpression antagonized the promoting effect of miR-542-3p on M. tuberculosis survival in macrophages by regulating autophagy.

Development and validation of the dialysis dementia risk score: A retrospective, population-based, nested case-control study.

BACKGROUND: Dementia is prevalent and underdiagnosed in the dialysis population. We aimed to develop and validate a simple dialysis dementia scoring system to facilitate identification of individuals who are at high risk for dementia. METHODS: We applied a retrospective, nested case-control study design using a national dialysis cohort derived from the National Health Insurance Research Database in Taiwan. Patients aged between 40 and 80 years were included and 2940 patients with incident dementia were matched to 29,248 non-dementia controls. All subjects were randomly divided into the derivation and validation sets with a ratio of 4:1. Conditional logistic regression models were used to identify factors contributing to the risk score. The cutoff value of the risk score was determined by Youden's J statistic and the graphic method. RESULTS: The dialysis dementia risk score (DDRS) finally included age and 10 comorbidities as risk predictors. The C-statistic of the model was 0.71 (95% confidence interval [CI] 0.70-0.72). Calibration revealed a strong linear relationship between predicted and observed dementia risk (R2  = 0.99). At a cutoff value of 50 points, the high-risk patients had an approximately three-fold increased risk of having dementia compared to those with low risk (odds ratio [OR] 3.03, 95% CI 2.78-3.31). The DDRS performance, including discrimination (C-statistic 0.71, 95% CI 0.69-0.73) and calibration (p value of Hosmer-Lemeshow test for goodness of fit = 0.18), was acceptable during validation. The OR value (2.82, 95% CI 2.37-3.35) was similar to those in the derivation set. CONCLUSION: The DDRS system has the potential to serve as an easily accessible screening tool to determine the high-risk groups who deserve subsequent neurological evaluation in daily clinical practice.

Psychometric properties of a novel instrument for evaluating indoor air pollution health literacy in adults.

This study aimed to develop and validate the psychometric properties of a novel instrument that measures Indoor Air Pollution Health Literacy (IAPHL). The qualitative phase was conducted to design questions based on the conceptual model of the European Health Literacy Survey Questionnaire. We developed a 38-item instrument covering 12 constructs, that is, four information competencies within three health domains to assess IAPHL. A cross-sectional online video survey of 647 adults aged 20 years and above in Taiwan was conducted. Various measures of validity and reliability coefficients were assessed to indicate the psychometric properties of the IAPHL instrument. The content validity indices for relevance, importance, and clarity of the 38 questions were 0.97, 0.96, and 0.89, respectively. The model fit indices obtained from the confirmatory factor analysis supported the acceptable structures of the theoretically hypothetical 12-factor model (standardized root mean square residual = 0.055; root mean square error of approximation = 0.065). Internal consistency for the instrument showed a Cronbach's alpha of 0.96. The IAPHL instrument developed in this study showed satisfactory validity and reliability and can be used in future fieldwork.

Guignardones Y-Z, Antiviral Meroterpenes from Penicillium sp. NBUF154 Associated with a Crella Sponge from the Marine Mesophotic Zone.

Guignardones Y-Z (1-2), two new meroterpenoids, and six known metabolites involving guignardones A-H (3-4), gyorgy-isoflavone (5), daidzein (6), blumenol A (7) and guignardianone A (8) were isolated from the fungus Penicillium sp. NBUF154, which was obtained from a 60 m deep Crella sponge. Their structures including absolute configurations were unambiguously elucidated by exhaustive spectroscopic analysis and ECD calculations. A putative biosynthetic pathway toward guignardones (1-4) is here proposed. Biological evaluation of compounds 1-8 showed that 1 and 7 exert potent inhibitory effects towards human enterovirus 71 (EV71).

Acremocholone, an Anti-Vibrio Steroid from the Marine Mesophotic Zone Ciocalypta Sponge-Associated Fungus Acremonium sp. NBUF150.

Mesophotic coral ecosystems (MCEs) represent an underexplored source of intriguing natural products. Efforts to discover bioactive metabolites from sponge-associated fungi in MCEs identified a new steroid, acremocholone (1) and its three known analogs (2-4), from Acremonium sp. NBUF150. The Acremonium sp. NBUF150 was isolated from a Ciocalypta sponge located 70 m deep within the South China Sea. The planar structures and absolute configuration of 1-4 were determined from NMR-derived spectroscopic data, HR-ESI-MS, and X-ray crystallography. Compound 1 exhibited antimicrobial inhibition against Vibrio scophthalmi, V. shilonii and V. brasiliensis at minimum inhibitory concentrations of 8 µg/mL; compound 2 inhibited V. shilonii and V. brasiliensis at 8 and 32 µg/mL, respectively, and compound 4 inhibited growth of V. brasiliensis at 16 µg/mL. Sponge associated fungi from MCEs represent a promising resource of anti-Vibrio drug leads for aquaculture use.

[Genetic analysis of a case with a supernumerary marker derived from chromosome 9].

OBJECTIVE: To delineate a small supernumerary marker chromosome (sSMC) derived from chromosome 9 with combined cytogenetic and molecular methods. METHODS: For a pregnant woman with fetal ultrasound revealing left ventricular punctate hyperechoic echo, and a high risk for monosomy or partial deletion of chromosome 8, chromosome 9 trisomy, monosomy or partial deletion of chromosome 11 by non-invasive prenatal testing, and an abnormal MOM value revealed by mid-term serum screening, amniocentesis was performed for G banded chromosomal analysis and single nucleotide polymorphism array (SNP-array) assay. Peripheral blood samples of the woman and her spouse were also collected for the above tests. In addition, the woman was further subjected to C banding karyotyping analysis and fluorescence in situ hybridization (FISH) assay. RESULTS: The G-banded karyotype of the pregnant women was 47,XX,+mar[20]/46,XX[80], whilst C-banding analysis showed a deep stain in the middle of the sSMC (suggestive of centromeric region) and light stain at both ends (suggestive of euchromatism). FISH combined with DAPI banding analysis using 9pter/9qter probes revealed a karyotype of 47,XX,+mar.ish i(9)(9p10)(9p++)[2]/46,XX[18], whilst SNP-array has revealed a 68.1 Mb duplication in the 9p24.3q13 region. A database search has suggested the duplication to be likely pathogenic. No abnormality was found in her fetus and spouse by karyotyping and SNP-array analysis. CONCLUSION: Through combined cytogenetic and molecular genetic analysis, a sSMC derived from chromosome 9 was delineated, which has enabled genetic counseling for the couple.