Targeted Drug Delivery for the Treatment of Abdominal Pain in Chronic Pancreatitis: A Retrospective Case Series.

Abdominal pain secondary to chronic pancreatitis (CP) is difficult to manage and often requires chronic oral opioid therapy (OOT). Targeted drug delivery (TDD) allows for a diminished dose of opioid intake and improved pain levels. TDD has been used in different pain syndromes with only limited reports in CP. OBJECTIVE: The objective of this article is to perform a retrospective review of CP patients treated with TDD versus OOT to compare chronic pain control and consumed morphine-equivalent doses. METHODS: Patients receiving TDD between September 2011 and August 2018 were included. All patients were weaned off oral opioids one week before intrathecal trial and pump implantation. Patients with intrathecal trials providing at least 50% pain relief underwent pump implantation. Data were collected while on OOT and at two weeks, three months, and nine months post-implant. Data were analyzed with Microsoft Excel 365 MSO using means and standard deviations. P-values were calculated using a two-tailed student's t-test with paired two-sample means. RESULTS: Twenty-three patients were analyzed. Pre-trial average pain score was 6.5/10 with a mean improvement with trials greater than 71%. The mean chronic baseline oral morphine milligram equivalents (MME) was 188. The mean MME on TDD at two weeks (0.36), three months (1.39), and nine months (2.47) were significantly lower than OOT. Mean pain scores were 6, 4.9, and 5.6 at two weeks, three months, and nine months, respectively, compared to 6.5 on OOT. DISCUSSION: The results of this study indicate that TDD provides improved pain control with significantly lower opioid doses.

Large-scale annotated dataset for cochlear hair cell detection and classification.

Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, rat, guinea pig, pig, primate, and human cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 107,000 hair cells which have been identified and annotated as either inner or outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair-cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to give other hearing research groups the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.

Conformation selection by ATP-competitive inhibitors and allosteric communication in ERK2.

Activation of the extracellular signal-regulated kinase-2 (ERK2) by phosphorylation has been shown to involve changes in protein dynamics, as determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) and NMR relaxation dispersion measurements. These can be described by a global exchange between two conformational states of the active kinase, named 'L' and 'R,' where R is associated with a catalytically productive ATP-binding mode. An ATP-competitive ERK1/2 inhibitor, Vertex-11e, has properties of conformation selection for the R-state, revealing movements of the activation loop that are allosterically coupled to the kinase active site. However, the features of inhibitors important for R-state selection are unknown. Here, we survey a panel of ATP-competitive ERK inhibitors using HDX-MS and NMR and identify 14 new molecules with properties of R-state selection. They reveal effects propagated to distal regions in the P+1 and helix αF segments surrounding the activation loop, as well as helix αL16. Crystal structures of inhibitor complexes with ERK2 reveal systematic shifts in the Gly loop and helix αC, mediated by a Tyr-Tyr ring stacking interaction and the conserved Lys-Glu salt bridge. The findings suggest a model for the R-state involving small movements in the N-lobe that promote compactness within the kinase active site and alter mobility surrounding the activation loop. Such properties of conformation selection might be exploited to modulate the protein docking interface used by ERK substrates and effectors.

Impaired endochondral ossification in a skeletally immature dog: implications for femoral cleft formation and suspected incomplete femoral ossification.

Historically, knowledge regarding congenital skeletal malformations in canines is poor. The Nomina Embryologica Veterinaria does not currently list any dysmorphia related to distal femoral fusion, and there is a significant absence of comprehensive descriptions of congenital defects in the veterinary literature. This paper reports on the radiographic and computed tomography (CT) characteristics of a skeletal abnormality in a seven-month-old crossbreed dog that presented for chronic right pelvic limb lameness as a result of secondary developmental patella luxation. Successful resolution of the lameness was achieved through concurrent surgical correction of the patella luxation and distal femoral cleft.

Informed consent-patients' understanding of risk.

AIMS: The central concept of informed consent is communication of the chance of a successful outcome. The risks and benefits are probabilistic concepts derived from populations; they do not map with any certainty to the individual. We tested patients' comprehension of basic probability concepts that are needed for informed consent. METHODS: Patients (n=478) completed five questions designed to test risk estimates that are relevant to informed consent. The questions posed non-medical scenarios to avoid patients associating them with their clinical care. The questionnaire was in English and was only offered to patients whose nurse felt that they had sufficient English literacy to understand the questions. RESULTS: Out of a possible total of five correct answers, Asian patients scored lowest, and significantly less than Pakeha/Europeans (average total score 2.6±1.7 vs 3.6±1.4, p<0.001, 95% confidence interval 0.5 to 1.38). The total score for Maori/Pasifika was intermediate (3.2±1.4), yet they had the lowest deprivation index. This discordant finding may be due to poorer English literacy among Asian participants. On multiple linear regression, Asian ethnicity and advancing age were the independent predictors of a low score. Socio-economic deprivation decile and sex were not. CONCLUSIONS: When answering questions constructed according to best practice, many (but not all) patients have reasonable risk comprehension. Further improvement could target older patients, those of Asian ethnicity and probably all patients where English is a second language. Liberal use of interpreters is suggested.

Signal-to-noise of linear and volume measures of left ventricular and left atrial size.

BACKGROUND: Serial echocardiographic assessments are common in clinical cardiology, e.g., for timing of intervention in mitral and aortic regurgitation. When following patients with serial echocardiograms, each new measurement is a combination of true change and confounding noise. The current investigation compares linear chamber dimensions with volume estimates of chamber size. The aim is to assess which measure is best for serial echocardiograms, when the ideal parameter will be sensitive to change in chamber size and have minimal spurious variation (noise). We present a method that disentangles true change from noise. Linear regression of chamber size against elapsed time gives a slope, being the ability of the method to detect change. Noise is the scatter of individual points away from the trendline, measured as the standard error of the slope. The higher the signal-to-noise ratio (SNR), the more reliably a parameter will distinguish true change from noise. METHODS: LV and LA parasternal dimensions and apical biplane volumes were obtained from serial clinical echocardiogram reports. Change over time was assessed as the slope of the linear regression line, and noise was assessed as the standard error of the regression slope. Signal-to-noise ratio is the slope divided by its standard error. RESULTS: The median number of LV studies was 5 (4-11) for LV over a mean duration of 5.9 ± 3.0 years in 561 patients (diastole) and 386 (systole). The median number of LA studies was 5 (4-11) over a mean duration of 5.3 ± 2.0 years in 137 patients. Linear estimates of LV size had better signal-to-noise than volume estimates (p < 0.001 for diastolic and p = 0.035 for systolic). For the left atrium, the difference was not significant (p = 0.214). This may be due to sample size; the effect size was similar to that for LV systolic size. All three parameters had a numerical value of signal-to-noise that favoured linear dimensions over volumes. CONCLUSION: Linear measures of LV size have better signal-to-noise than volume measures. There was no difference in signal-to-noise between linear and volume measures of LA size, although this may be a Type II error. The use of regression lines may be better than relying on single measurements. Linear dimensions may clarify whether changes in volumes are real or spurious.

Unsupervised machine learning identifies distinct ALS molecular subtypes in post-mortem motor cortex and blood expression data.

Amyotrophic lateral sclerosis (ALS) displays considerable clinical and genetic heterogeneity. Machine learning approaches have previously been utilised for patient stratification in ALS as they can disentangle complex disease landscapes. However, lack of independent validation in different populations and tissue samples have greatly limited their use in clinical and research settings. We overcame these issues by performing hierarchical clustering on the 5000 most variably expressed autosomal genes from motor cortex expression data of people with sporadic ALS from the KCL BrainBank (N = 112). Three molecular phenotypes linked to ALS pathogenesis were identified: synaptic and neuropeptide signalling, oxidative stress and apoptosis, and neuroinflammation. Cluster validation was achieved by applying linear discriminant analysis models to cases from TargetALS US motor cortex (N = 93), as well as Italian (N = 15) and Dutch (N = 397) blood expression datasets, for which there was a high assignment probability (80-90%) for each molecular subtype. The ALS and motor cortex specificity of the expression signatures were tested by mapping KCL BrainBank controls (N = 59), and occipital cortex (N = 45) and cerebellum (N = 123) samples from TargetALS to each cluster, before constructing case-control and motor cortex-region logistic regression classifiers. We found that the signatures were not only able to distinguish people with ALS from controls (AUC 0.88 ± 0.10), but also reflect the motor cortex-based disease process, as there was perfect discrimination between motor cortex and the other brain regions. Cell types known to be involved in the biological processes of each molecular phenotype were found in higher proportions, reinforcing their biological interpretation. Phenotype analysis revealed distinct cluster-related outcomes in both motor cortex datasets, relating to disease onset and progression-related measures. Our results support the hypothesis that different mechanisms underpin ALS pathogenesis in subgroups of patients and demonstrate potential for the development of personalised treatment approaches. Our method is available for the scientific and clinical community at https://alsgeclustering.er.kcl.ac.uk .

Charge and lipophilicity are required for effective block of the hair-cell mechano-electrical transducer channel by FM1-43 and its derivatives.

The styryl dye FM1-43 is widely used to study endocytosis but behaves as a permeant blocker of the mechano-electrical transducer (MET) channel in sensory hair cells, loading rapidly and specifically into the cytoplasm of hair cells in a MET channel-dependent manner. Patch clamp recordings of mouse outer hair cells (OHCs) were used to determine how a series of structural modifications of FM1-43 affect MET channel block. Fluorescence microscopy was used to assess how the modifications influence hair-cell loading in mouse cochlear cultures and zebrafish neuromasts. Cochlear cultures were also used to evaluate otoprotective potential of the modified FM1-43 derivatives. Structure-activity relationships reveal that the lipophilic tail and the cationic head group of FM1-43 are both required for MET channel block in mouse cochlear OHCs; neither moiety alone is sufficient. The extent of MET channel block is augmented by increasing the lipophilicity/bulkiness of the tail, by reducing the number of positive charges in the head group from two to one, or by increasing the distance between the two charged head groups. Loading assays with zebrafish neuromasts and mouse cochlear cultures are broadly in accordance with these observations but reveal a loss of hair-cell specific labelling with increasing lipophilicity. Although FM1-43 and many of its derivatives are generally cytotoxic when tested on cochlear cultures in the presence of an equimolar concentration of the ototoxic antibiotic gentamicin (5 µM), at a 10-fold lower concentration (0.5 µM), two of the derivatives protect OHCs from cell death caused by 48 h-exposure to 5 µM gentamicin.

Conformation Selection by ATP-competitive Inhibitors and Allosteric Communication in ERK2.

Activation of the extracellular signal regulated kinase-2 (ERK2) by phosphorylation has been shown to involve changes in protein dynamics, as determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) and NMR relaxation dispersion measurements. These can be described by a global exchange between two conformational states of the active kinase, named "L" and "R", where R is associated with a catalytically productive ATP-binding mode. An ATP-competitive ERK1/2 inhibitor, Vertex-11e, has properties of conformation selection for the R-state, revealing movements of the activation loop that are allosterically coupled to the kinase active site. However, the features of inhibitors important for R-state selection are unknown. Here we survey a panel of ATP-competitive ERK inhibitors using HDX-MS and NMR and identify 14 new molecules with properties of R-state selection. They reveal effects propagated to distal regions in the P+1 and helix αF segments surrounding the activation loop, as well as helix αL16. Crystal structures of inhibitor complexes with ERK2 reveal systematic shifts in the Gly loop and helix αC, mediated by a Tyr-Tyr ring stacking interaction and the conserved Lys-Glu salt bridge. The findings suggest a model for the R-state involving small movements in the N-lobe that promote compactness within the kinase active site and alter mobility surrounding the activation loop. Such properties of conformation selection might be exploited to modulate the protein docking interface used by ERK substrates and effectors.

Large-scale annotated dataset for cochlear hair cell detection and classification.

Our sense of hearing is mediated by cochlear hair cells, localized within the sensory epithelium called the organ of Corti. There are two types of hair cells in the cochlea, which are organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains a few thousands of hair cells, and their survival is essential for our perception of sound because they are terminally differentiated and do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. However, the sheer number of cells along the cochlea makes manual quantification impractical. Machine learning can be used to overcome this challenge by automating the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, human, pig and guinea pig cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 90'000 hair cells, all of which have been manually identified and annotated as one of two cell types: inner hair cells and outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to supply other groups within the hearing research community with the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease.

SOD1-ALS-Browser: a web-utility for investigating the clinical phenotype in SOD1 amyotrophic lateral sclerosis.

Objective: Variants in the superoxide dismutase (SOD1) gene are among the most common genetic causes of amyotrophic lateral sclerosis. Reflecting the wide spectrum of putatively deleterious variants that have been reported to date, it has become clear that SOD1-linked ALS presents a highly variable age at symptom onset and disease duration.Methods: Here we describe an open access web tool for comparative phenotype analysis in ALS: https://sod1-als-browser.rosalind.kcl.ac.uk/. The tool contains a built-in dataset of clinical information from 1383 people with ALS harboring a SOD1 variant resulting in one of 162 unique amino acid sequence alterations and from a non-SOD1 comparator ALS cohort of 13,469 individuals. We present two examples of analyses possible with this tool, testing how the ALS phenotype relates to SOD1 variants that alter amino acid residue hydrophobicity and to distinct variants at the 94th residue of SOD1, where six are sampled.Results and conclusions: The tool provides immediate access to the datasets and enables bespoke analysis of phenotypic trends associated with different protein variants, including the option for users to upload their own datasets for integration with the server data. The tool can be used to study SOD1-ALS and provides an analytical framework to study the differences between other user-uploaded ALS groups and our large reference database of SOD1 and non-SOD1 ALS. The tool is designed to be useful for clinicians and researchers, including those without programming expertise, and is highly flexible in the analyses that can be conducted.

Empirical mode decomposition of the atmospheric flows and pollutant transport over real urban morphology.

The momentum transport and pollutant dispersion in the atmospheric surface layer (ASL) are governed by a broad spectrum of turbulence structures. Whereas, their contributions have not been explicitly investigated in the context of real urban morphology. This paper aims to elucidate the contributions from different types of eddies in the ASL over a dense city to provide the reference of urban planning, realizing more favorable ventilation and pollutant dispersion. The building-resolved large-eddy simulation dataset of winds and pollutants over the Kowloon downtown, Hong Kong, is decomposed into a few intrinsic mode functions (IMFs) via empirical mode decomposition (EMD). EMD is a data-driven algorithm that has been successfully implemented in many research fields. The results show that four IMFs are generally enough to capture most of the turbulence structures in real urban ASL. In particular, the first two IMFs, which are initiated by individual buildings, capture the small-scale vortex packets that populate within the irregular building clusters. On the other hand, the third and fourth IMFs capture the large-scale motions (LSMs) detached to the ground surface that are highly efficient in transport. They collectively contribute to nearly 40% of vertical momentum transport even with relatively low vertical turbulence kinetic energy (TKE). LSMs are long, streaky structures that mainly consist of streamwise TKE components. It is found that the open areas and regular streets promote the portion of streamwise TKE in LSMs, improving the vertical momentum transport and pollutant dispersion. In addition, these streaky LSMs are found to play a crucial role in pollutant dilution in the near field after the pollutant source, while the small-scale vortex packets are more efficient in transport in the mid-field and far-field.

Contamination of tea leaves by anthraquinone: The atmosphere as a possible source.

The detection of anthraquinone in tea leaves has raised concerns due to a potential health risk associated with this species. This led the European Union to impose a maximum residue limit (MRL) of 0.02 mg/kg for anthraquinone in dried tea leaves. As atmospheric contamination has been identified as one of the possible sources of anthraquinone residue, this study investigates the contamination resulting from the deposition of atmospheric anthraquinone using a global chemical transport model that accounts for the emission, atmospheric transport, chemical transformation, and deposition of anthraquinone on the surface. The largest contribution to the global atmospheric budget of anthraquinone is from residential combustion followed by the secondary formation from oxidation of anthracene. Simulations suggest that atmospheric anthraquinone deposition could be a substantial source of the anthraquinone found on tea leaves in several tea-producing regions, especially near highly industrialized and populated areas of southern and eastern Asia. The high level of anthraquinone deposition in these areas may result in residues in tea products exceeding the EU MRL. Additional contamination could also result from local tea production operations.

Visualizing Collagen Fibrils in the Cochlea's Tectorial and Basilar Membranes Using a Fluorescently Labeled Collagen-Binding Protein Fragment.

PURPOSE: A probe that binds to unfixed collagen fibrils was used to image the shapes and fibrous properties of the TM and BM. The probe (CNA35) is derived from the bacterial adhesion protein CNA. We present confocal images of hydrated gerbil TM, BM, and other cochlear structures stained with fluorescently labeled CNA35. A primary purpose of this article is to describe the use of the CNA35 collagen probe in the cochlea. METHODS: Recombinant poly-histidine-tagged CNA35 was expressed in Escherichia coli, purified by cobalt-affinity chromatography, fluorescence labeled, and further purified by gel filtration chromatography. Cochleae from freshly harvested gerbil bullae were irrigated with and then incubated in CNA35 for periods ranging from 2 h - overnight. The cochleae were fixed, decalcified, and dissected. Isolated cochlear turns were imaged by confocal microscopy. RESULTS: The CNA35 probe stained the BM and TM, and volumetric imaging revealed the shape of these structures and the collagen fibrils within them. The limbal zone of the TM stained intensely. In samples from the cochlear base, intense staining was detected on the side of the TM that faces hair cells. In the BM pectinate zone, staining was intense at the upper and lower boundaries. The BM arcuate zone was characterized by a prominent longitudinal collagenous structure. The spiral ligament, limbus and lamina stained for collagen, and within the spiral limbus the habenula perforata were outlined with intense staining. CONCLUSION: The CNA35 probe provides a unique and useful view of collagenous structures in the cochlea.

A critical period of prehearing spontaneous Ca2+ spiking is required for hair-bundle maintenance in inner hair cells.

Sensory-independent Ca2+ spiking regulates the development of mammalian sensory systems. In the immature cochlea, inner hair cells (IHCs) fire spontaneous Ca2+ action potentials (APs) that are generated either intrinsically or by intercellular Ca2+ waves in the nonsensory cells. The extent to which either or both of these Ca2+ signalling mechansims are required for IHC maturation is unknown. We find that intrinsic Ca2+ APs in IHCs, but not those elicited by Ca2+ waves, regulate the maturation and maintenance of the stereociliary hair bundles. Using a mouse model in which the potassium channel Kir2.1 is reversibly overexpressed in IHCs (Kir2.1-OE), we find that IHC membrane hyperpolarization prevents IHCs from generating intrinsic Ca2+ APs but not APs induced by Ca2+ waves. Absence of intrinsic Ca2+ APs leads to the loss of mechanoelectrical transduction in IHCs prior to hearing onset due to progressive loss or fusion of stereocilia. RNA-sequencing data show that pathways involved in morphogenesis, actin filament-based processes, and Rho-GTPase signaling are upregulated in Kir2.1-OE mice. By manipulating in vivo expression of Kir2.1 channels, we identify a "critical time period" during which intrinsic Ca2+ APs in IHCs regulate hair-bundle function.

Wavelet analysis of the atmospheric flows over real urban morphology.

Winds are the basic forces for atmospheric transport such as pollutant removal and pedestrian thermal comfort. The transport capability is commonly measured in terms of length and velocity scales. In this connection, the flows in the atmospheric surface layer (ASL) over the Kowloon Peninsula, Hong Kong (HK) are scrutinized by the large-eddy simulation (LES) to characterize the motion scales over real urban morphology. Apart from statistical analysis, the streamwise fluctuating velocity u' is examined by both wavelet and energy spectrum in which a primary peak is consistently shown at streamwise wavelength 70 m ≤ λx ≤ 300 m. A secondary peak at a longer wavelength 800 m ≤ λx ≤ 3000 m, however, is unveiled by wavelet only. It denotes the existence of intermittent turbulence structures whose sizes are much larger than those of buildings. Further wavelet analysis reveals that majority energy-carrying eddies are enlarging (tens to hundreds of meters) from the roughness sublayer (RSL) to the inertial sublayer (ISL). Analogous to its smooth-wall and schematic rough-wall counterparts, the turbulence kinetic energy (TKE) over urban areas is peaked in the ISL which is carried by eddies of size 50 m ≤ λx ≤ 1000 m. The (horizontal) spatial distribution of energy-carrying eddies is further visualized to compare the crucial motion scales in the RSL and ISL. Finally, conditional sampling is used to demystify the contribution to vertical momentum flux u'w' in terms of streamwise wavelength and quadrants. The results advance our fundamental understanding of ASL transport processes, fostering sustainable environmental policy.

AAV-mediated rescue of Eps8 expression in vivo restores hair-cell function in a mouse model of recessive deafness.

The transduction of acoustic information by hair cells depends upon mechanosensitive stereociliary bundles that project from their apical surface. Mutations or absence of the stereociliary protein EPS8 cause deafness in humans and mice, respectively. Eps8 knockout mice (Eps8 -/- ) have hair cells with immature stereocilia and fail to become sensory receptors. Here, we show that exogenous delivery of Eps8 using Anc80L65 in P1-P2 Eps8 -/- mice in vivo rescued the hair bundle structure of apical-coil hair cells. Rescued hair bundles correctly localize EPS8, WHIRLIN, MYO15, and BAIAP2L2, and generate normal mechanoelectrical transducer currents. Inner hair cells with normal-looking stereocilia re-expressed adult-like basolateral ion channels (BK and KCNQ4) and have normal exocytosis. The number of hair cells undergoing full recovery was not sufficient to rescue hearing in Eps8 -/- mice. Adeno-associated virus (AAV)-transduction of P3 apical-coil and P1-P2 basal-coil hair cells does not rescue hair cells, nor does Anc80L65-Eps8 delivery in adult Eps8 -/- mice. We propose that AAV-induced gene-base therapy is an efficient strategy to recover the complex hair-cell defects in Eps8 -/- mice. However, this therapeutic approach may need to be performed in utero since, at postnatal ages, Eps8 -/- hair cells appear to have matured or accumulated damage beyond the point of repair.

Investigating the Antituberculosis Activity of Selected Commercial Essential Oils and Identification of Active Constituents Using a Biochemometrics Approach and In Silico Modeling.

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis which has become prevalent due to the emergence of resistant M. tuberculosis strains. The use of essential oils (EOs) as potential anti-infective agents to treat microbial infections, including TB, offers promise due to their long historical use and low adverse effects. The current study aimed to investigate the in vitro anti-TB activity of 85 commercial EOs, and identify compounds responsible for the activity, using a biochemometrics approach. A microdilution assay was used to determine the antimycobacterial activity of the EOs towards some non-pathogenic Mycobacterium strains. In parallel, an Alamar blue assay was used to investigate antimycobacterial activity towards the pathogenic M. tuberculosis strain. Chemical profiling of the EOs was performed using gas chromatography-mass spectrometry (GC-MS) analysis. Biochemometrics filtered out putative biomarkers using orthogonal projections to latent structures discriminant analysis (OPLS-DA). In silico modeling was performed to identify potential therapeutic targets of the active biomarkers. Broad-spectrum antimycobacterial activity was observed for Cinnamomum zeylanicum (bark) (MICs = 1.00, 0.50, 0.25 and 0.008 mg/mL) and Levisticum officinale (MICs = 0.50, 0.5, 0.5 and 0.004 mg/mL) towards M. smegmatis, M. fortuitum, M. gordonae and M. tuberculosis, respectively. Biochemometrics predicted cinnamaldehyde, thymol and eugenol as putative biomarkers. Molecular docking demonstrated that cinnamaldehyde could serve as a scaffold for developing a novel class of antimicrobial compounds by targeting FtsZ and PknB from M. tuberculosis.

Is atmospheric oxidation capacity better in indicating tropospheric O3 formation?

Tropospheric ozone (O3) concentration is increasing in China along with dramatic changes in precursor emissions and meteorological conditions, adversely affecting human health and ecosystems. O3 is formed from the complex nonlinear photochemical reactions from nitrogen oxides (NO x = NO + NO2) and volatile organic compounds (VOCs). Although the mechanism of O3 formation is rather clear, describing and analyzing its changes and formation potential at fine spatial and temporal resolution is still a challenge today. In this study, we briefly summarized and evaluated different approaches that indicate O3 formation regimes. We identify that atmospheric oxidation capacity (AOC) is a better indicator of photochemical reactions leading to the formation of O3 and other secondary pollutants. Results show that AOC has a prominent positive relationship to O3 in the major city clusters in China, with a goodness of fit (R 2) up to 0.6. This outcome provides a novel perspective in characterizing O3 formation and has significant implications for formulating control strategies of secondary pollutants.

GEOexplorer: a webserver for gene expression analysis and visualisation.

Gene Expression Omnibus (GEO) is a database repository hosting a substantial proportion of publicly available high throughput gene expression data. Gene expression analysis is a powerful tool to gain insight into the mechanisms and processes underlying the biological and phenotypic differences between sample groups. Despite the wide availability of gene expression datasets, their access, analysis, and integration are not trivial and require specific expertise and programming proficiency. We developed the GEOexplorer webserver to allow scientists to access, integrate and analyse gene expression datasets without requiring programming proficiency. Via its user-friendly graphic interface, users can easily apply GEOexplorer to perform interactive and reproducible gene expression analysis of microarray and RNA-seq datasets, while producing a wealth of interactive visualisations to facilitate data exploration and interpretation, and generating a range of publication ready figures. The webserver allows users to search and retrieve datasets from GEO as well as to upload user-generated data and combine and harmonise two datasets to perform joint analyses. GEOexplorer, available at https://geoexplorer.rosalind.kcl.ac.uk, provides a solution for performing interactive and reproducible analyses of microarray and RNA-seq gene expression data, empowering life scientists to perform exploratory data analysis and differential gene expression analysis on-the-fly without informatics proficiency.