Cellular data extraction from multiplexed brain imaging data using self-supervised Dual-loss Adaptive Masked Autoencoder.

Reliable large-scale cell detection and segmentation is the fundamental first step to understanding biological processes in the brain. The ability to phenotype cells at scale can accelerate preclinical drug evaluation and system-level brain histology studies. The impressive advances in deep learning offer a practical solution to cell image detection and segmentation. Unfortunately, categorizing cells and delineating their boundaries for training deep networks is an expensive process that requires skilled biologists. This paper presents a novel self-supervised Dual-Loss Adaptive Masked Autoencoder (DAMA) for learning rich features from multiplexed immunofluorescence brain images. DAMA's objective function minimizes the conditional entropy in pixel-level reconstruction and feature-level regression. Unlike existing self-supervised learning methods based on a random image masking strategy, DAMA employs a novel adaptive mask sampling strategy to maximize mutual information and effectively learn brain cell data. To the best of our knowledge, this is the first effort to develop a self-supervised learning method for multiplexed immunofluorescence brain images. Our extensive experiments demonstrate that DAMA features enable superior cell detection, segmentation, and classification performance without requiring many annotations. In addition, to examine the generalizability of DAMA, we also experimented on TissueNet, a multiplexed imaging dataset comprised of two-channel fluorescence images from six distinct tissue types, captured using six different imaging platforms. Our code is publicly available at https://github.com/hula-ai/DAMA.

Carboxyhemoglobin in Cardiac Surgery Patients and Its Association with Risk Factors and Biomarkers of Hemolysis.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with hemolysis. Yet, there is no easily available and frequently measured marker to monitor this hemolysis. However, carboxyhemoglobin (CO-Hb), formed by the binding of carbon monoxide (a product of heme breakdown) to hemoglobin, may reflect such hemolysis. We hypothesized that CO-Hb might increase after cardiac surgery and show associations with operative risk factors and indirect markers for hemolysis. METHODS: We conducted a retrospective descriptive cohort study of data from on-pump cardiac surgery patients. We analyzed temporal changes in CO-Hb levels and applied a generalized linear model to assess patient characteristics associated with peak CO-Hb levels. Additionally, we examined their relationship with red blood cell (RBC) transfusion and bilirubin levels. RESULTS: We studied 38,487 CO-Hb measurements in 1735 patients. CO-Hb levels increased significantly after cardiac surgery, reaching a peak CO-Hb level 2.1 times higher than baseline (P < .001) at a median of 17 hours after the initiation of surgery. Several factors were independently associated with higher peak CO-Hb, including age (P < .001), preoperative respiratory disease (P = .001), New York Heart Association Class IV (P = .019), the number of packed RBC transfused (P < .001), and the duration of CPB (P = .002). Peak CO-Hb levels also significantly correlated with postoperative total bilirubin levels (Rho = 0.27, P < .001). CONCLUSIONS: CO-Hb may represent a readily obtainable and frequently measured biomarker that has a moderate association with known biomarkers of and risk factors for hemolysis in on-pump cardiac surgery patients. These findings have potential clinical implications and warrant further investigation.

Conamonin A and dihydrochalcones from the whole plants of Conamomum rubidum (Lamxay & N.S.Lý) Skornick. & A.D. Poulsen showing anti-inflammatory and cytotoxic activities.

A new compound, conamonin A (1), was isolated from the whole plants of Conamomum rubidum with eight known dihydrochalcones (2-9). Their structures were elucidated by a combination of spectroscopic methods as well as by comparison with previously reported data. The absolute configuration of 1 was assigned by TDDFT-ECD method. Compounds 1 and 8 showed inhibitory activity against LPS-induced NO production in the RAW 264.7 cells, with IC50 values of 58.29 ± 2.88 and 81.77 ± 5.99 µM, respectively. Compounds 3/4 and 5/6 exhibited inhibitory effects, with IC50 values of 28.76 ± 1.16 and 29.89 ± 1.79 µg/mL, respectively. Compounds 2, 7-9 exhibited significant cytotoxic activity against human lung carcinoma (the SK-LU-1 cell line) with IC50 values ranging from 9.87 to 17.99 µM. This study offers valuable insights into the chemical constituents and biological activities of Conamomum rubidum, highlighting its potential as a source for discovering new anti-inflammatory and cytotoxic agents.

Conarubins A-D: Four Monoterpene-Chalcone Conjugates from Conamomum rubidum and Their Anti-inflammatory and Cytotoxic Activities.

Four novel compounds, conarubins A-D (1-4), were isolated from the whole plants of Conamomum rubidum collected in Vietnam. Their structures were elucidated by extensive spectroscopic analyses and by quantum chemical calculations of NMR and ECD. Compounds 1 and 2 were the first examples of monoterpene-monoterpene-chalcone conjugates in nature, whereas compound 4 was an unprecedented monoterpene-substituted chalcone containing a 3,4,5-trioxygenated cyclohexa-2,5-diene-1-one ring. The anti-inflammatory and cytotoxic activities of all isolates were investigated.

Influence of titanium dioxide and composite on the accuracy of an intraoral scanner for bilateral upper posterior edentulous jaw (Kennedy class I) scanning: An in vitro study.

OBJECTIVES: The accuracy of 3-dimensional images produced by the intraoral scanner (IOS) is affected by scanning-aid materials. This in vitro study aimed to elucidate the influence of scanning-aid materials on the accuracy (trueness and precision) of digital scanning on the bilateral upper posterior edentulous jaw (Kennedy class I). METHODS: The asymmetrical bilateral upper posterior edentulous model (reference model) was generated using a 3D printer with three groups (application of TiO2 powder - composite and no-treatment control). The experimental scans were executed (n = 10 per group) using TRIOS3 (3shape), while one reference scan was obtained by an industrial scanner (Solutionix - C500). Values of trueness and precision were evaluated using the 3D superimposition method on mean deviation values. The accuracy was assessed using mean deviation values following the 3D superimposition method. RESULTS: IOS had high trueness (20.6 µm), and significant differences were found between the no-treatment and TiO2 groups. Considering the cut-off value of deviations as 300 µm for clinical acceptability, the analysis clarified the most variations in the control group. There was a significant difference between the no-treatment group and others in the maxillary tuberosity area relating to long-span edentulous. The composite group had the best precision values (1.1 µm). Significant differences were found between composite and TiO2 groups (2.7 µm). CONCLUSIONS: The bilateral upper posterior edentulous jaw digital impressions obtained using IOS were accurate. However, the digital images in the palate and maxillary tuberosity area related to long-span edentulous differed significantly. TiO2-containing powder and composite landmarks affected the accuracy and stability of the IOS. CLINICAL SIGNIFICANCE: Scanning aid materials can increase the accuracy of the bilateral upper posterior edentulous jaw scanning with IOS.

Chemical composition and acetylcholinesterase inhibitory activity of essential oil from the leaves of Mitrephora poilanei Weeras. & R.M.K. Saunders.

The present study provides the first information on the chemical composition and acetylcholinesterase inhibitory activity of the essential oil (EO) from the leaves of Mitrephora poilanei Weeras. & R.M.K.Saunders from Vietnam. Gas chromatography and gas chromatography-mass spectrometry analysis revealed that the main components of the M. poilanei EO were ß-caryophyllene (13.2%), α-humulene (10.5%), germacrene D (8.1%), ß-elemene (5.2%) and bicyclogermacrene (5.1%). The anti-acetylcholinesterase assay showed that the EO displayed moderate activity with IC50 value of 31.16 ± 3.06 µg/mL. These findings proposed that the plant can be exploited for its anti-acetylcholinestrate potential.

Structure revision and absolute configuration of 5,7-diepi-2α-hydroxyoplopanone and anti-osteoporotic activities of sesquiterpenoids from the rhizomes of Homalomena pendula.

Five sesquiterpenoids including 2α-hydroxyoplopanone (1), oplopanone (2), 1ß,4ß,6α-trihydroxy-eudesmane (3), 1ß,4ß,7α-trihydroxy-eudesmane (4) and bullatantriol (5) were isolated from Homalomena pendula. The structure of the previously reported compound, 5,7-diepi-2α-hydroxyoplopanone (1a), has been revised to 1 by the spectroscopic evidences (1D-/2D-NMR, IR, UV and HRESIMS) and by comparison between experimental and theoretical NMR data using DP4+ protocol. Furthermore, the absolute configuration of 1 was unambiguously assigned by ECD experiments. Compounds 2 and 4 displayed a potent ability to stimulate osteogenic differentiation of MC3T3-E1 cells at 4 µg/mL (by 123.74% and 131.07%, respectively) and 20 µg/mL (by 112.45% and 126.41%, respectively) whilst 3 and 5 did not show any activities. At 20 µg/mL, 4 and 5 significantly promoted the mineralization of MC3T3-E1 cells with values of 112.95% and 116.37%, respectively, whereas 2 and 3 were inactive. The results indicated that 4 could be an excellent component for anti-osteoporosis studies from the rhizomes of H. pendula.

A Survey of Antibiotic Use During Insertion of Cardiovascular Implantable Devices Among United States Implanters.

Antibiotic use for cardiovascular implantable devices (CIED) prophylaxis is well-accepted despite a paucity of data. Pre-procedural prophylaxis lowers the rate of CIED infections; however, data is lacking for intra- or post-procedural antibiotic use. Antibiotic-eluting envelopes (ENVELOPE) [TYRX®TM] have been shown to reduce post-procedural infections. Understanding implanter practices may provide insight as to the need for antibiotic stewardship. The purpose of this survey was to assess the practices of implanters nationally. A survey was completed by 150 implanters across the US. Participants were board certificated, implanters of CIEDs, with varying experience (1-25 years), in various hospital settings. Of the respondents, 97% reported routine use of systemic antibiotics pre-operatively. About two-thirds of implanters continue systemic antibiotics post-operatively, with half continuing antibiotics for >24 h; 83% of implanters add antibiotic to saline for the purpose of irrigating the wound; 55% routinely use ENVELOPE on approximately 38% of patients. Common reasons cited for ENVELOPE use were infection concerns, significant risk factors, prior device infection, and immunosuppressed status. Two-thirds of respondents use systemic antibiotics during generator changes, with >50% continuing antibiotics for >24 h. This study suggests wide variations in practice among implanters. Additional attention to existing guidelines and evidence regarding appropriate use of ENVELOPE is still needed.

How well do covariates perform when adjusting for sampling bias in online COVID-19 research? Insights from multiverse analyses.

COVID-19 research has relied heavily on convenience-based samples, which-though often necessary-are susceptible to important sampling biases. We begin with a theoretical overview and introduction to the dynamics that underlie sampling bias. We then empirically examine sampling bias in online COVID-19 surveys and evaluate the degree to which common statistical adjustments for demographic covariates successfully attenuate such bias. This registered study analysed responses to identical questions from three convenience and three largely representative samples (total N = 13,731) collected online in Canada within the International COVID-19 Awareness and Responses Evaluation Study ( www.icarestudy.com ). We compared samples on 11 behavioural and psychological outcomes (e.g., adherence to COVID-19 prevention measures, vaccine intentions) across three time points and employed multiverse-style analyses to examine how 512 combinations of demographic covariates (e.g., sex, age, education, income, ethnicity) impacted sampling discrepancies on these outcomes. Significant discrepancies emerged between samples on 73% of outcomes. Participants in the convenience samples held more positive thoughts towards and engaged in more COVID-19 prevention behaviours. Covariates attenuated sampling differences in only 55% of cases and increased differences in 45%. No covariate performed reliably well. Our results suggest that online convenience samples may display more positive dispositions towards COVID-19 prevention behaviours being studied than would samples drawn using more representative means. Adjusting results for demographic covariates frequently increased rather than decreased bias, suggesting that researchers should be cautious when interpreting adjusted findings. Using multiverse-style analyses as extended sensitivity analyses is recommended.

Development of optimized protocol for culturing African swine fever virus field isolates in MA104 cells.

The goal of this study was to identify a candidate commercial cell line for the replication of African swine fever virus (ASFV) by comparing several available cell lines with various medium factors. In the sensitivity test of cells, MA104 and MARC-145 had strong potential for ASFV replication. Next, MA104 cells were used to compare the adaptation of ASFV obtained from tissue homogenates and blood samples in various infectious media. At the 10th passage, the ASFV obtained from the blood sample had a significantly higher viral load than that obtained from the tissue sample (P = 0.000), exhibiting a mean cycle threshold (Ct) value = 20.39 ± 1.99 compared with 25.36 ± 2.11. For blood samples, ASFV grew on infectious medium B more robustly than on infectious medium A (P = 0.006), corresponding to a Ct value = 19.58 ± 2.10 versus 21.20 ± 1.47. African swine fever virus originating from blood specimens continued to multiply gradually and peaked in the 15th passage, exhibiting a Ct value = 14.36 ± 0.22 in infectious medium B and a Ct value = 15.42 ± 0.14 in infectious medium A. When ASFV was cultured from tissue homogenates, however, there was no difference (P = 0.062) in ASFV growth between infectious media A and B. A model was developed to enhance ASFV replication through adaptation to MA104 cells. The lack of mutation at the genetic segments encoding p72, p54, p30, and the central hypervariable region (CVR) in serial culture passages is important in increasing the probability of maintaining immunogenicity when developing a vaccine candidate.

L'objectif de cette étude était d'identifier une lignée cellulaire commerciale candidate pour la réplication du virus de la peste porcine africaine (ASFV) en comparant plusieurs lignées cellulaires disponibles et différents milieux. Lors du test de sensibilité des cellules, MA104 et MARC-145 présentaient un fort potentiel pour la réplication d'AFSV. Par la suite, les cellules MA104 ont été utilisées pour comparer l'adaptation d'ASFV obtenu d'homogénats de tissus et d'échantillons de sang dans différents milieux. Au dixième passage, l'ASFV obtenu de l'échantillon de sang avait une charge virale significativement plus élevée que celle obtenue de l'échantillon de tissu (P = 0,000), avec une valeur seuil moyenne de cycles (Ct) de 20,39 ± 1,99 comparativement à 25,36 ± 2,11. Pour les échantillons sanguins, l'ASFV a poussé sur le milieu B de manière plus robuste que sur le milieu A (P = 0,006), ce qui correspond à une valeur Ct de 19,58 ± 2,10 versus 21,20 ± 1,47. L'ASFV provenant des échantillons sanguins continua de se multiplier graduellement et atteignit un pic au 15e passage, avec une valeur Ct de 14,36 ± 0,22 dans le milieu B et une valeur Ct de 15,42 ± 0,14 dans le milieu A. Toutefois, lorsque l'ASFV fut cultivé à partir des homogénats de tissus, il n'y avait pas de différence (P = 0,062) dans la croissance d'ASFV entre les milieux A et B. Un modèle a été développé pour augmenter la réplication d'ASFV par adaptation aux cellules MA104. L'absence de mutation au segment génétique codant pour p72, p54, p30, et la région hypervariable centrale (CVR) dans des passages en série en culture est importante en augmentant la probabilité de maintenir une immunogénicité lors du développement d'un vaccin candidat.(Traduit par Docteur Serge Messier).

Psychological distress and its association with intake of sugar-sweetened beverages, discretionary foods, and alcohol in women during the COVID-19 pandemic in Australia.

OBJECTIVES: This study aimed to explore psychological distress, lifestyle, and demographic factors, as well as their relationship to discretionary choices in women of reproductive age during the coronavirus disease 2019 pandemic in Australia. METHODS: Reproductive-aged women (18-50 y) in Australia participated in a national online survey. Psychological distress score (using a validated 10-item Kessler Psychological Distress Scale questionnaire) was the primary exposure of interest, and key outcomes were frequencies of discretionary choices (sugar-sweetened beverages [SSBs], alcohol, and discretionary foods). Sociodemographic and physical activity data were also collected. Logistic regression was used to report adjusted odds ratio (aOR) and 95% confidence interval to predict SSBs (less than weekly; most days/daily), total discretionary foods (none/<2 times/d; ≥3 times/d), and alcohol use (never/less than monthly; most weeks/daily). RESULTS: A total of 1005 women were included in the study, of whom 40% had a high level of psychological distress. Women with high psychological distress (aOR: 1.96; 95% CI, 1.32-2.91) and those who gained weight during the pandemic (aOR: 1.71; 95% CI, 1.10-2.65) were more likely to consume discretionary foods ≥3 times/d. There was no association between psychological distress and SSB intake or alcohol; however, Australian, New Zealander, or Pacific Islander background (aOR: 1.68; 95% CI, 1.21-2.33) and more hours of sitting time (aOR: 1.88; 95% CI, 1.07-3.29) were associated with SSB consumption on most days/daily. Older age (aOR: 1.70; 95% CI, 1.00-2.89), higher household income (aOR: 1.44; 95% CI, 1.08-1.92), and moderate or high physical activity (aOR: 1.75; 95% CI, 1.10-2.80) were associated with alcohol intake on most weeks/daily. CONCLUSIONS: Public health messaging to promote healthy eating should take into account the effect of psychological distress on health behavior. Messages aimed at maintaining a positive relationship between food intake and mental wellbeing, particularly among vulnerable groups, are warranted.

L2pB1 Cells Contribute to Tumor Growth Inhibition.

Natural IgM (nIgM) antibodies play critical roles in cancer immunosurveillance. However, the role of B-1 B cells, the lymphocytes that produce nIgM, remains to be elucidated. L2pB1 cells, a subpopulation of B-1 B cells, have a unique poly-self-reactive nIgM repertoire and are capable of phagocytosis, potent antigen presentation, and immunomodulation. Using an inducible knock-in and knockout mouse model, we investigated the effect of the loss of L2pB1 cells in a B16F10 melanoma model. Our results show active tumor infiltration of L2pB1 cells in wild type mice, and conversely, depletion of L2pB1 cells results in larger tumor mass and increased angiogenesis. In vitro analysis revealed that L2pB1 cells contribute to the growth inhibition of melanoma cells in both 2D cell culture and 3D tumor spheroids. Similar effects were observed in an MC38 murine colon cancer model. Moreover, our data suggest that one of the ways that L2pB1 cells can induce tumor cell death is via lipoptosis. Lastly, we tested whether L2pB1 cell-derived monoclonal nIgM antibodies can specifically recognize tumor spheroids. Nine of the 28 nIgM-secreting L2pB1 clones demonstrated specific binding to tumor spheroids but did not bind control murine embryonic fibroblasts. Our study provides evidence that L2pB1 cells contribute to cancer immunity through their unique nIgM repertoire, tumor recognition, and lipoptosis. Taken together, because of their ability to recognize common features of tumors that are independent of genetic mutations, L2pB1 cells and their nIgM could be potential candidates for cancer treatment that can overcome tumor heterogeneity-associated drug resistance.

Age-related viral load and severity of systemic pathological lesions in acute naturally occurring African swine fever virus genotype II infections.

African swine fever (ASF) causes a contagious hemorrhagic disease in all ages of pigs without sex predilections. The objective of this study was to determine the age-related viral loads and severity of systemic pathological lesions among three different swine group ages (weaned pigs, fattening pigs, and sows) during a recent outbreak of acute ASF in Vietnam. Age-related viral loads were determined in 5 major organs (lung, liver, spleen, kidney, and lymph node) by immunohistochemistry as well as in the blood by real-time polymerase chain reaction (PCR). Age-related systemic pathological lesions were analyzed in the listed organs among three age groups. Weaned pigs had significantly (p < 0.05) higher levels of viral loads in their lung, liver, lymph nodes and blood than in those of fattening pigs and sows. Fattening pigs had significantly (p < 0.05) higher scores of macroscopic lung and lymphoid lesions, and microscopic liver lesions compared with those of weaned pigs and sows. The results of this study demonstrated that viral loads were age-related in acute naturally occurring ASF but the severity of pathological lesions was not correlated with the level of viral loads in the five major organs.

High utilisers of emergency departments: the profile and journey of patients with mental health issues.

OBJECTIVE: Frequent presenters to the Emergency Department (ED) are known to have complex physical, behavioural and social needs. The study aimed to analyse the system's behaviour to generate new insights into ED high utilisers with complex mental health issues. METHODS: A retrospective cohort study of the ED presentations of 200 high utilisers during a 12-month period was conducted. Analyses included psychiatric diagnoses, re-presentation rates, cost-benefit analysis of services and patient journey maps to illustrate the patient experience. RESULTS: The profiled high utilisers represented nearly a quarter of total ED mental health presentations and were more likely to be single and unemployed. Diagnostically, Borderline Personality Disorder and Schizophrenia predominated. The re-presentation rate was high (70% within 28 days) and mental health attributable costs represented nearly three quarters of total health costs. CONCLUSION: The study revealed a disintegrated service system for ED high utilisers with mental health issues, resulting in suboptimal clinical outcomes and substantial costs. To deliver value-based mental healthcare our lessons were; (1) stabilise the system's interaction with the patient by ensuring service responses are consistent with their enhanced management plan (2) all the system's parts channel the patient into various support services including psychological treatment with one therapist.KEY POINTSThe top 200 high utilisers presented to emergency 1928 times within 12 monthsThe re-presentation rate amongst the study's cohort was high (70% within 28 days)A high prevalence of BPD and schizophrenia was noted for this cohortThe study reveals a disintegrated service system for ED high utilisers, resulting in suboptimal clinical outcomes and substantial costs for the serviceA need for early identification, consistency in service responses and various support services to be provided by the hospital including psychological treatment.

The Isolation and Replication of African Swine Fever Virus in Primary Renal-Derived Swine Macrophages.

African swine fever virus (ASFV) causes hemorrhagic disease in domestic pigs by replicating mainly in monocyte/macrophage lineages. Various primary cells including pulmonary alveolar macrophages have been used for the propagation of ASFV on this account. However, ethical constraints and consistency problems exist as it is necessary to harvest same phenotype of primary cells in order to continue a study. We suggested renal-derived swine macrophages as a novel primary cell candidate to address these issues. These primary cells proved to be permissive to both cell adapted ASFV and a wild-type ASFV. Compared to the commercial cell line MA-104, the renal-derived macrophages were more suitable to isolate the field virus. The consistent molecular characteristics of the renal-derived macrophages were demonstrated by immunocytochemistry with antibodies against macrophage cell surface markers including CD163, CD172a, and Iba-1. Viral protein p30 and p72 expression in ASFV infected macrophages was confirmed by immunocytochemistry by use of specific monoclonal antibodies. We observed increase of cell-free viral DNA and infectious virus titer in infected cell supernatant in successive days-post-infection. These results demonstrated that primary renal-derived swine macrophages are useful for ASFV isolation and propagation in terms of cell phenotypes, susceptibility to the virus, and virus production.

Three new steroidal saponins from Aspidistra letreae plants and their cytotoxic activities.

Three new steroidal saponins, aspiletreins A-C (1-3), together with 2H-chromen-2-one (4), and α-tocopherol (5), were isolated from whole Aspidistra letreae plants collected in Vietnam. Their structures were elucidated by a combination of spectroscopic analyses, including 1D- and 2D-NMR, IR, and HRESIMS, and by comparison with the reported data in the literature. Compounds 1-3 exhibited moderate cytotoxicities against the LU-1, HeLa, MDA-MB-231, HepG2, and MKN-7 human cancer cell lines, with IC50 values ranging from 7.69 ± 0.40 to 20.46 ± 3.11 µM.

A new sterol from the Vietnamese marine sponge Xestospongia testudinaria and its biological activities.

A new sterol, langcosterol A (1), together with two known sterols 2 and 3, were isolated from the marine sponge Xestospongia testudinaria collected in Vietnam. Their chemical structures were elucidated on the basis of extensive spectroscopic analyses and comparisons with published data. The new compound 1 and the known compound 3 exhibited moderate cytotoxic activities against three human cancer cell lines (A549, lung cancer; MCF7, breast cancer; HeLa, cervical cancer) and a human normal cell line (WI-38 fibroblast), with IC50 values ranging from 29.0 to 68.0 µM.

Three new sesquiterpene aminoquinones from a Vietnamese Spongia sp. and their biological activities.

Sesquiterpenoid quinones with remarkable properties, such as anti-inflammatory, antibacterial, antiviral, antitumor, antiangiogenic, and differentiation-inducing activities, have reportedly been isolated from the marine sponge genera Dysidea, Spongia, and Dactylospongia. In our continuing search for bioactive compounds from marine sponges, three new sesquiterpenoid quinones, langcoquinones D-F (1-3), were isolated from the ethyl acetate extract of Spongia sp. collected from Vietnam. Their chemical structures were elucidated on the basis of extensive spectroscopic analyses. The newly isolated compounds 1-3 were assessed for their antibacterial activities against Gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus, and Gram-negative bacteria, Klebsiella pneumoniae and Escherichia coli, as well as their cytotoxic activities against three human cancer cell lines (A549, lung cancer; MCF7, breast cancer; HeLa, cervical cancer) and a human normal cell line (WI-38 fibroblast). All compounds were inactive against the Gram-negative bacteria. Furthermore, langcoquinones E (2) and F (3) lacked antibacterial activities against the Gram-positive bacteria and cytotoxic activities against the tested cell lines. However, langcoquinone D (1) exhibited good antibacterial activities against Bacillus subtilis and Staphylococcus aureus, with MIC values of 12.5 and 25.0 µM, respectively. Furthermore, 1 exhibited significant cytotoxic activities against three human cancer cell lines (A549, lung cancer; MCF7, breast cancer; HeLa, cervical cancer) and a human normal cell line (WI-38 fibroblast).

A new triterpene ester and other chemical constituents from the aerial parts of Anodendron paniculatum and their cytotoxic activity.

The aim of the research was to study the active constituents of Anodendron paniculatum Roxb. (Apocynaceae). A new triterpene ester, named anopaniester (1), and cycloartenol (2), ursolic acid (3), esculenic acid (4), bis-(2-ethylhexyl) phthalate (5), desmosterol (6), stigmasterol (7), vaniline (8), and (E)-phytol (9), were isolated from the aerial parts of A. paniculatum. Compounds 3 and 6 showed the significant inhibitory effect (IC50 values ranging from 30.89 ± 3.60 to 44.37 ± 5.40 µg/ml) against tested human cancer cell lines LU-1 and MKN-7. The compounds 1-4, and 6 were isolated from this genus Anodendron for the first time.

Spatial transcriptomes within the Pseudomonas aeruginosa biofilm architecture.

Bacterial cooperative associations and dynamics in biofilm microenvironments are of special interest in recent years. Knowledge of localized gene-expression and corresponding bacterial behaviors within the biofilm architecture at a global scale has been limited, due to a lack of robust technology to study limited number of cells in stratified layers of biofilms. With our recent pioneering developments in single bacterial cell transcriptomic analysis technology, we generated herein an unprecedented spatial transcriptome map of the mature in vitro Pseudomonas aeruginosa biofilm model, revealing contemporaneous yet altered bacterial behaviors at different layers within the biofilm architecture (i.e., surface, middle and interior of the biofilm). Many genes encoding unknown functions were highly expressed at the biofilm-solid interphase, exposing a critical gap in the knowledge of their activities that may be unique to this interior niche. Several genes of unknown functions are critical for biofilm formation. The in vivo importance of these unknown proteins was validated in invertebrate (fruit fly) and vertebrate (mouse) models. We envisage the future value of this report to the community, in aiding the further pathophysiological understanding of P. aeruginosa biofilms. Our approach will open doors to the study of bacterial functional genomics of different species in numerous settings.