Cold mediates maize root hair developmental plasticity via epidermis-specific transcriptomic responses.

Cold stress during early development limits maize (Zea mays L.) production in temperate zones. Low temperatures restrict root growth and reprogram gene expression. Here, we provide a systematic transcriptomic landscape of maize primary roots, their tissues, and cell types in response to cold stress. The epidermis exhibited a unique transcriptomic cold response, and genes involved in root hair formation were dynamically regulated in this cell type by cold. Consequently, activation of genes involved in root hair tip growth contributed to root hair recovery under moderate cold conditions. The maize root hair defective mutants roothair defective 5 (rth5) and roothair defective 6 (rth6) displayed enhanced cold tolerance with respect to primary root elongation. Furthermore, dehydration response element-binding protein 2.1 (dreb2.1) was the only member of the dreb subfamily of AP2/EREB transcription factor genes upregulated in primary root tissues and cell types but exclusively downregulated in root hairs upon cold stress. Plants overexpressing dreb2.1 significantly suppressed root hair elongation after moderate cold stress. Finally, the expression of rth3 was regulated by dreb2.1 under cold conditions, while rth6 transcription was regulated by dreb2.1 irrespective of the temperature regime. We demonstrated that dreb2.1 negatively regulates root hair plasticity at low temperatures by coordinating the expression of root hair defective genes in maize.

Laser capture microdissection transcriptome (LCM RNA-seq) reveals BcDFR is a key gene in anthocyanin synthesis of non-heading Chinese cabbage.

BACKGROUND: Purple non-heading Chinese cabbage [Brassica campestris (syn. Brassica rapa) ssp. chinensis] has become popular because of its richness in anthocyanin. However, anthocyanin only accumulates in the upper epidermis of leaves. Further studies are needed to investigate the molecular mechanisms underlying the specific accumulation of it. RESULTS: In this study, we used the laser capture frozen section method (LCM) to divide purple (ZBC) and green (LBC) non-heading Chinese cabbage leaves into upper and lower epidermis parts (Pup represents the purple upper epidermis, Plow represents the purple lower epidermis, Gup represents the green upper epidermis, Glow represents the green lower epidermis). Through transcriptome sequencing, we found that the DIHYDROFLAVONOL 4-REDUCTASE-encoding gene BcDFR, is strongly expressed in Pup but hardly in others (Plow, Gup, Glow). Further, a deletion and insertion in the promoter of BcDFR in LBC were found, which may interfere with BcDFR expression. Subsequent analysis of gene structure and conserved structural domains showed that BcDFR is highly conserved in Brassica species. The predicted protein-protein interaction network of BcDFR suggests that it interacts with almost all functional proteins in the anthocyanin biosynthesis pathway. Finally, the results of the tobacco transient expression also demonstrated that BcDFR promotes the synthesis and accumulation of anthocyanin. CONCLUSIONS: BcDFR is specifically highly expressed on the upper epidermis of purple non-heading Chinese cabbage leaves and regulates anthocyanin biosynthesis and accumulation. Our study provides new insights into the functional analysis and transcriptional regulatory network of anthocyanin-related genes in purple non-heading Chinese cabbage.

Advancements in differentiation between sperm cells and epithelial cells for efficient forensic DNA analysis in sexual assault cases.

Most of the sexual assault casework samples are of mixed sources. Forensic DNA laboratories are always in the requirement of a precise technique for the efficient separation of sperm and non-sperm DNA from mixed samples. Since the introduction of the differential extraction technique in 1985, it has seen significant advancements in the form of either chemicals used or modification of incubation times. Several automated and semi-automated techniques have also adopted the fundamentals of conventional differential extraction techniques. However, lengthy incubation, several manual steps, and carryover over non-sperm material in sperm fraction are some of the major limitations of this technique. Advanced cell separation techniques have shown huge promise in separating sperm cells from a mixture based on their size, shape, composition, and membrane structure and antigens present on sperm membranes. Such advanced techniques such as DEParray, ADE, FACS, LCM, HOT and their respective pros and cons have been discussed in this article. As current-day forensic techniques should be as per the line of Olympic slogan i.e., faster, higher, stronger, the advanced cell separation techniques show a huge potential to be implemented in the casework samples.

A linear compensation method for inference accuracy improvement of memristive in-memory computing.

Memristive computing system (MCS), with the feature of in-memory computing capability, for artificial neural networks (ANNs) deployment showing low power and massive parallelism, is a promising alternative for traditional Von-Neumann architecture computing system. However, because of the various non-idealities of both peripheral circuits and memristor array, the performance of the practical MCS tends to be significantly reduced. In this work, a linear compensation method (LCM) is proposed for the performance improvement of MCS under the effect of non-idealities. By considering the effects of various non-ideal states in the MCS as a whole, the output error of the MCS under different conditions is investigated. Then, a mathematic model for the output error is established based on the experimental data. Furthermore, the MCS is researched at the physical circuit level as well, in order to analyze the specific way in which the non-idealities affect the output current. Finally, based on the established mathematical model, the LCM output current is compensated in real time to improve the system performance. The effectiveness of LCM is verified and showing outstanding performance in the residual neural network-34 network architecture, which is easily affected by the non-idealities in hardware. The proposed LCM can be naturally integrated into the operation processes of MCS, paving the way for optimizing the deployment on generic ANN hardware based on the memristor.

3D printing of ultra-thin veneers made of lithium disilicate using the LCM method in a digital workflow: A feasibility study.

OBJECTIVE: This article highlights the feasibility of the additive fabrication of ultra-thin veneers made of lithium disilicate using the lithography-based ceramic manufacturing (LCM) method. CLINICAL CONSIDERATIONS: An esthetical appealing restoration of anterior teeth with thin ceramic veneers is considered one of the ultimate challenges in restorative dental prosthetics. These sophisticated restorations can be fabricated in different ways. Both analog and digital subtractive manufacturing processes have been used to date. Either of the methods is highly demanding for the dental technician and dental engineering due to the required low ceramic layer thickness. CONCLUSION: Modern additive manufacturing methods, for example LCM technology, enable the production of ultra-thin lithium disilicate veneers with layer thicknesses of down to 0.2 mm and could therefore represent a viable alternative for this indication in the future. CLINICAL SIGNIFICANCE: Digital technologies can help streamline workflows, make the outcome more predictable and reproducible, and even further optimize therapeutic restorative options such as highly esthetic veneers for anterior teeth. The reduced material thickness allows for a true non-prep solution or minimally invasive preparation.

Negative Emotional Reactivity and Somatic Symptoms during Adolescence Predict Adult Health and Wellbeing in Early and Middle Adulthood.

Longitudinal research is lacking with respect to how negative emotional reactivity and somatic symptoms during adolescence set the stage for later health. The aim of this longitudinal study was to examine within-person associations between negative emotional reactivity and somatic symptoms during adolescence and their effects on health and wellbeing in adulthood. Participants (N = 1527; 48.3% female) were assessed annually at the age of 12 to 16 years and at the age of 35 and 45 years. Adolescents with frequent somatic symptoms reported higher reactivity. Individual differences in levels and changes of somatic symptoms and reactivity were independently associated with adult health and wellbeing decades later. The findings underscore the importance of considering how individual differences change during adolescent development.

Comparative evaluation of low-cost ceramic membrane and polymeric micro membrane in algal membrane photobioreactor for wastewater treatment.

Algal-bacterial membrane photobioreactor (AMPBR) is proven as a highly energy-efficient process for treating domestic wastewater. This study compared the application of polymeric micro-membrane (PMM) and a low-cost ceramic membrane (LCM) to the AMPBR process for treating domestic wastewater with low and high organic pollution levels. Experiments were conducted over 57 days using two PMM-AMPBRs and two LCM-AMPBRs, operating on a 12-h dark/light cycle in a continuous mode. Simulated wastewater containing varying levels of chemical oxygen demand (COD) was fed to reactors for a consistent hydraulic residence time (HRT) of 7 d and a flux rate of 100 L/m2/d. PMM and LCM-AMPBRs demonstrated efficient wastewater treatment capabilities, achieving COD removal rates exceeding 94% and 95% for high and low COD loadings, respectively. PMM-AMPBR achieved 54.1% TN removal at low COD loading, while LCM-AMPBR achieved 57.2%. These removal efficiencies decreased to 45.6% and 47.0% under high COD loading. Total Phosphorus (TP) removal reached 29-33% for PMM-AMPBRs and 21-24% for LCM-AMPBRs, irrespective of COD loading. LCM-AMPBRs showed significantly lower fouling frequency than PMM-AMPBRs. The biomass production rate decreased with increasing COD loading and achieved 40 mg/L/d at low COD loading for both AMPBRs. Net energy return (NER) values for both AMPBRs were close to 0.87, indicating them as energy-efficient processes. Considering the cost-effectiveness and comparable performance, LCM-AMPBR could be a viable alternative to PMM-AMPBR for wastewater treatment, particularly under low COD loading conditions.

Wear behaviour of lithography ceramic manufactured dental zirconia.

OBJECTIVE: The study aims to evaluate the wear surface using 3D surface roughness and other material characterization of zirconia fabricated using photopolymerization based Lithography-based Ceramic Manufacturing (LCM). METHOD: LCM technology was used to fabricate zirconia specimens of size 10 × 10 × 2mm3. Scanning Electron Microscope, 3D-profilometer, X-ray Diffraction, and hardness test characterized the samples before and after wear and Coefficient of friction (COF) was monitored. RESULT: The COF was around 0.7 and did not differ much between the horizontally and vertically printed specimens. However, the surface roughness after wear for horizontally printed specimen was 0.567 ± 0.139 µm, while that for vertically printed specimen was 0.379 ± 0.080 µm. The reduced valley depth and the dale void volume were low for the vertically printed zirconia specimen, indicating lesser voids and low fluid retention. In addition, it was observed that the hardness value of the vertically printed sample was better. The scanning electron microscopic images and 3D surface profiles of the zirconia specimens depicted the surface topography and revealed the wear track. CONCLUSION: The study shows that zirconia fabricated using LCM technology possesses surface roughness of about 0.5 µm with no machining scars that are usually associated with CAD/CAM dentistry and also indicating agreement with clinically acceptable values for minimal surface roughness of dental restorations. Dental restorations using LCM fabricated zirconia redues the requirement of post-processing work flow that is part of CAD/CAM dentistry.

Scenario modeling to predict changes in land use/cover using Land Change Modeler and InVEST model: a case study of Karaj Metropolis, Iran.

Models for land cover/land use simulation are appropriate and important tools for decision-makers, helping them build future plausible landscape scenarios. Due to the fact that the simulation results of different models may be different, it is sometimes difficult for users to choose a suitable model. Therefore, in this study, an integrated approach is used, combining the data obtained from remote sensing and GIS with Land Change Modeler (LCM) and Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) models to simulate and predict land cover/land use changes for 2028 in Karaj metropolis (Northern Iran as a poor region-in terms of data-which is under intense and rapid urbanization. In this sense, three land cover/land use maps related to the study area were primarily generated using satellite image data for the period 2006, 2011, and 2017. They were used as a basis to define two scenarios: business-as-usual (BAU) scenario and participatory plausible scenario (PPS) for 2028. Afterwards, the necessary input data used in running of both models were prepared and, then, the outputs of the models were interpreted and compared. According to the results, while human-made coverage and low-density grasslands increased by about 74% and 12%, respectively, it was from 2006 to 2017 that agricultural lands, gardens, and high-density grasslands decreased by 42%, 34%, and 7%, respectively. According to the business-as-usual scenario, which was projected using the LCM model, the increase in human-made cover will continue by about 29% by 2028, and the reduction rate of agricultural lands, gardens, and low-dense and dense grasslands will experience decrease by about 20%, 3%, 11%, and 9%, respectively. The participatory plausible scenario for 2028, which was defined using the InVEST model, confirmed the same results, but having different quantities. Accordingly, while human-made cover will increase by about 73%, the reduction rate of agricultural lands, gardens, and low-dense and dense grasslands will decrease by about 41%, 10%, 16%, and 1%, respectively. The output quantities of InVEST scenario model seem to be closer to reality with less uncertainty, because this model estimates the quantity of demand for land and its suitability for different uses, based on the views of different stakeholders, and considers landscape development future policies and plans. In contrast, the LCM model is based solely on trend extrapolation from the past to current time and changes in the landscape structure.

Assessing land use changes' effect on river water quality in the Dez Basin using land change modeler.

Changes in land use due to urbanization, industrialization, and agriculture will adversely affect water quality at all scales. This study examined the possible effects of future land use on the water quality of the Dez River located in Iran. The QUAL2Kw dynamic model was used to simulate the water quality of the Dez River. Data and information available in July 2019 and 2013 were used for calibration and validation. According to the comparison of the RMSE, RMSE%, and percent bias error indices for the model during the calibration and validation period, the QUAL2Kw model of Dez River had high accuracy with acceptable values of errors. The land use changes in the Dez river basin were modeled and predicted by the LCM model after simulating water quality. The images from Landsat 8/OLI were used for 2013, 2016, and 2019, respectively. Based on the accurate evaluation of classified images, Kappa coefficients for 2013, 2016, and 2019 were 88.19, 87.46, and 89.91, respectively. Modeling land use and land cover changes was conducted to predict 2030. As a result of the study, agricultural and built-up areas and water bodies will increase in 2030. The possible effects of land use changes in 2030 on river water quality were examined as a final step. Based on the results of the water quality simulation in 2030, biochemical oxygen demand, chemical oxygen demand, and NO3 parameters exceeded the maximum permissible level of drinking standard. This study recommends frequent water quality monitoring and LULC planning and management to reduce pollution in river basins.

In-Depth Mass Spectrometry-Based Proteomics of Formalin-Fixed, Paraffin-Embedded Tissues with a Spatial Resolution of 50-200 µm.

Formalin-fixed, paraffin-embedded (FFPE) tissues are banked in large repositories to cost-effectively preserve valuable specimens for later study. With the rapid growth of spatial proteomics, FFPE tissues can serve as a more accessible alternative to more commonly used frozen tissues. However, extracting proteins from FFPE tissues is challenging due to cross-links formed between proteins and formaldehyde. Here, we have adapted the nanoPOTS sample processing workflow, which was previously applied to single cells and fresh-frozen tissues, to profile protein expression from FFPE tissues. Following the optimization of extraction solvents, times, and temperatures, we identified an average of 1312 and 3184 high-confidence master proteins from 10 µm thick FFPE-preserved mouse liver tissue squares having lateral dimensions of 50 and 200 µm, respectively. The observed proteome coverage for FFPE tissues was on average 88% of that achieved for similar fresh-frozen tissues. We also characterized the performance of our fully automated sample preparation and analysis workflow, termed autoPOTS, for FFPE spatial proteomics. This modified nanodroplet processing in one pot for trace samples (nanoPOTS) and fully automated processing in one pot for trace sample (autoPOTS) workflows provides the greatest coverage reported to date for high-resolution spatial proteomics applied to FFPE tissues. Data are available via ProteomeXchange with identifier PXD029729.

Complexity untwined: The structure and function of cucumber (Cucumis sativus L.) shoot phloem.

Cucurbit phloem is complex, with large sieve tubes on both sides of the xylem (bicollateral phloem), and extrafascicular elements that form an intricate web linking the rest of the vasculature. Little is known of the physical interconnections between these networks or their functional specialization, largely because the extrafascicular phloem strands branch and turn at irregular angles. Here, export in the phloem from specific regions of the lamina of cucumber (Cucumis sativus L.) was mapped using carboxyfluorescein and 14 C as mobile tracers. We also mapped vascular architecture by conventional microscopy and X-ray computed tomography using optimized whole-tissue staining procedures. Differential gene expression in the internal (IP) and external phloem (EP) was analyzed by laser-capture microdissection followed by RNA-sequencing. The vascular bundles of the lamina form a nexus at the petiole junction, emerging in a predictable pattern, each bundle conducting photoassimilate from a specific region of the blade. The vascular bundles of the stem interconnect at the node, facilitating lateral transport around the stem. Elements of the extrafascicular phloem traverse the stem and petiole obliquely, joining the IP and EP of adjacent bundles. Using pairwise comparisons and weighted gene coexpression network analysis, we found differences in gene expression patterns between the petiole and stem and between IP and EP, and we identified hub genes of tissue-specific modules. Genes related to transport were expressed primarily in the EP while those involved in cell differentiation and development as well as amino acid transport and metabolism were expressed mainly in the IP.

Progesterone differentially affects the transcriptomic profiles of cow endometrial cell types.

BACKGROUND: The endometrium is a heterogeneous tissue composed of luminal epithelial (LE), glandular epithelial (GE), and stromal cells (ST), experiencing progesterone regulated dynamic changes during the estrous cycle. In the cow, this regulation at the transcriptomic level was only evaluated in the whole tissue. This study describes specific gene expression in the three types of cells isolated from endometrial biopsies following laser capture microdissection and the transcriptome changes induced by progesterone in GE and ST cells. RESULTS: Endometrial LE, GE, and ST cells show specific transcriptomic profiles. Most of the differentially expressed genes (DEGs) in response to progesterone are cell type-specific (96%). Genes involved in cell cycle and nuclear division are under-expressed in the presence of progesterone in GE, highlighting the anti-proliferative action of progesterone in epithelial cells. Elevated progesterone concentrations are also associated with the under-expression of estrogen receptor 1 (ESR1) in GE and oxytocin receptor (OXTR) in GE and ST cells. In ST cells, transcription factors such as SOX17 and FOXA2, known to regulate uterine epithelial-stromal cross-talk conveying to endometrial receptivity, are over-expressed under progesterone influence. CONCLUSIONS: The results from this study show that progesterone regulates endometrial function in a cell type-specific way, which is independent of the expression of its main receptor PGR. These novel insights into uterine physiology present the cell compartment as the physiological unit rather than the whole tissue.

Laser Capture Microdissection: A Gear for Pancreatic Cancer Research.

The advancement in molecular techniques has been attributed to the quality and significance of cancer research. Pancreatic cancer (PC) is one of the rare cancers with aggressive behavior and a high mortality rate. The asymptomatic nature of the disease until its advanced stage has resulted in late diagnosis as well as poor prognosis. The heterogeneous character of PC has complicated cancer development and progression studies. The analysis of bulk tissues of the disease was insufficient to understand the disease, hence, the introduction of the single-cell separating technique aided researchers to decipher more about the specific cell population of tumors. This review gives an overview of the Laser Capture Microdissection (LCM) technique, one of the single-cell separation methods used in PC research.

Life cycle management in bakeries: a proposed roadmap towards sustainability.

PURPOSE: Some commercial/industrial sectors have increased their interest in sustainability, in some cases changing their business focus, from a profit-centered approach to a more balanced view, including environmental and social factors. It means that the interest in sustainability is increasing. Life cycle management (LCM) is a methodology/concept that can contribute to this paradigm shift. In this research, the potential application of LCM in the bakery segment was investigated, considering the entire value chain related to the sector (inputs, packaging, suppliers, customers, waste management). METHODS: Bakeries were visited, in Teresina, Piauí, Brazil, to learn about the products, services, production processes, and the socio-environmental and economic sustainability practices, aiming at identifying bottlenecks and to propose alternatives based on LCM. Besides the field approach, the study was structured based on the literature that brings the concepts and potentialities of applying LCM in various economic/industrial sectors. The PDCA cycle and the SWOT Matrix were also used to assist the implementation of LCM. A roadmap was proposed aiming at the LCM implementation in bakeries. RESULTS: The results show that although the sector has some environmentally sustainable practices (waste separation, energy savings, reuse of products, inputs purchased locally), the primary intention is to reduce costs and not to mitigate environmental impacts. Regarding social responsibility, they donate bread to institutions. This is an important attitude, but not the only one for fulfilling the social role within the value chain. They do not consider suppliers that show concern for the environment (certified companies), and both marketing and product labels do not evoke these issues too. CONCLUSIONS AND RECOMMENDATIONS: Thus, there is the possibility of implementing LCM in bakeries if there is a concern with sustainable production and consumption. A roadmap for implementing LCM in bakeries was proposed including some steps: mapping the life cycle of products/processes/services associated with the sector; analyzing factors that can influence the actions towards sustainability; disseminating life cycle information to the entire value chain; efficient waste management, including the partnership with recycling companies; and treatment of the collected data and improvement proposal, using management tools such as the PDCA Cycle, the SWOT Matrix, and Environmental, Social and Governance (ESG) aiming at the search for environmental and economic sustainability and social fair alternatives. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11367-021-02008-7.

Analysis of the transcriptome of bovine endometrial cells isolated by laser micro-dissection (2): impacts of post-partum negative energy balance on stromal, glandular and luminal epithelial cells.

BACKGROUND: In post-partum dairy cows, the energy needs to satisfy high milk production induces a status of more or less pronounced Negative Energy Balance (NEB). NEB associated with fat mobilization impairs reproductive function. In a companion paper, we described constitutive gene expression in the three main endometrial cell types (stromal, glandular and luminal epithelial cells) isolated by laser capture micro-dissection (LCM) showing the specificities of their transcriptomic profiles. This study investigates the specific impact of NEB on gene expression in these cells around 80 days after parturition at day 15 of the oestrus cycle and describes their specific response to NEB. RESULTS: Following the description of their constitutive expression, the transcriptome profiles obtained by RNA sequencing of the three cells types revealed that differences related to the severity of NEB altered mainly specific patterns of expression related to individual cell types. Number of differentially expressed genes between severe NEB (SNEB) and mild NEB (MNEB) cows was higher in ST than in LE and GE, respectively. SNEB was associated with differential expression of genes coding for proteins involved in metabolic processes and embryo-maternal interactions in ST. Under-expression of genes encoding proteins with functions related to cell structure was found in GE whereas genes encoding proteins participating in pro-inflammatory pathways were over-expressed. Genes associated to adaptive immunity were under-expressed in LE. CONCLUSION: The severity of NEB after calving is associated with changes in gene expression around 80 days after parturition corresponding to the time of breeding. Specific alterations in GEs are associated with activation of pro-inflammatory mechanisms. Concomitantly, changes in the expression of genes encoding proteins involved in cell interactions and maternal recognition of pregnancy takes place in ST. The combination of these effects possibly altering the uterine environment and embryo maternal interactions may negatively influence the establishment of pregnancy.

Analysis of the transcriptome of bovine endometrial cells isolated by laser micro-dissection (1): specific signatures of stromal, glandular and luminal epithelial cells.

BACKGROUND: A number of studies have examined mRNA expression profiles of bovine endometrium at estrus and around the peri-implantation period of pregnancy. However, to date, these studies have been performed on the whole endometrium which is a complex tissue. Consequently, the knowledge of cell-specific gene expression, when analysis performed with whole endometrium, is still weak and obviously limits the relevance of the results of gene expression studies. Thus, the aim of this study was to characterize specific transcriptome of the three main cell-types of the bovine endometrium at day-15 of the estrus cycle. RESULTS: In the RNA-Seq analysis, the number of expressed genes detected over 10 transcripts per million was 6622, 7814 and 8242 for LE, GE and ST respectively. ST expressed exclusively 1236 genes while only 551 transcripts were specific to the GE and 330 specific to LE. For ST, over-represented biological processes included many regulation processes and response to stimulus, cell communication and cell adhesion, extracellular matrix organization as well as developmental process. For GE, cilium organization, cilium movement, protein localization to cilium and microtubule-based process were the only four main biological processes enriched. For LE, over-represented biological processes were enzyme linked receptor protein signaling pathway, cell-substrate adhesion and circulatory system process. CONCLUSION: The data show that each endometrial cell-type has a distinct molecular signature and provide a significantly improved overview on the biological process supported by specific cell-types. The most interesting result is that stromal cells express more genes than the two epithelial types and are associated with a greater number of pathways and ontology terms.

Therapeutic Potential of Fosmanogepix (APX001) for Intra-abdominal Candidiasis: from Lesion Penetration to Efficacy in a Mouse Model.

Intra-abdominal candidiasis (IAC) is one of the most common yet underappreciated forms of invasive candidiasis. IAC is difficult to treat, and therapeutic failure and drug-resistant breakthrough infections are common in some institutions despite the use of echinocandins as first-line agents. Fosmanogepix (FMGX, formerly APX001) is a first-in-class antifungal prodrug that can be administered both intravenously and orally. FMGX is currently in phase 2 clinical development for the treatment of life-threatening invasive fungal infections. To explore the pharmacological properties and therapeutic potential of FMGX for IAC, we evaluated both drug penetration and efficacy of the active moiety manogepix (MGX, formerly APX001A) in liver tissues in a clinically relevant IAC mouse model infected with Candida albicans Matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) and laser capture microdissection (LCM)-directed absolute drug quantitation were employed to evaluate drug penetration into liver abscess lesions both spatially and quantitatively. The partitioning of MGX into lesions occurred slowly after a single dose; however, robust accumulation in the lesion was achieved after 3 days of repeated dosing. Associated with this drug penetration pattern, reduction in fungal burden and clearance in the liver were observed in mice receiving the multiday FMGX regimen. In comparison, administration of micafungin resulted in marginal reduction in fungal burden at the end of 4 days of treatment. These results suggest that FMGX is a promising candidate for the treatment of IAC.

Land use/land cover and climate change interaction in the derived savannah region of Nigeria.

The interaction of land use/land cover (LULC) and climate change, to a large extent, involves anthropogenic activities. This study was carried out in the derived savannah of Nigeria, a delicate, transition ecological zone between the rainforest and savanna zones where the interaction of LULC and climate change could be well appreciated. Using the remote sensing and GIS, Land Change Modeler (LCM), and multivariate geostatistics tools, the study evaluated coupled interaction between LULC and climate change and assessed the changes in the land use/land cover patterns for the periods 1972, 1986, 2002, and 2019. It also evaluated the present (1941-2019) and future (2020-2050) variability in rainfall patterns and made an attempt to predict the interaction between LULC and climate change in future climate. The results suggest that the urban (built-up) area, waterbody, woodland, and farmland experienced a rapid increase of about 2,400%, 583%, 277%, and 32%, respectively, while the forest cover lost about 39% between 1972 and 2019. Furthermore, the study predicted 46% and 29% reduction in the forested area between 2002 and 2050 and 2019 and 2050, respectively. The study concludes that rainfall will be the major driver of LULC change within the study area under a future climate.

Penetration of Ibrexafungerp (Formerly SCY-078) at the Site of Infection in an Intra-abdominal Candidiasis Mouse Model.

Ibrexafungerp (IBX), formerly SCY-078, is a novel, oral and intravenous, semisynthetic triterpenoid glucan synthase inhibitor in clinical development for treating multiple fungal infections, including invasive candidiasis. Intra-abdominal candidiasis (IAC) is one of the most common types of invasive candidiasis associated with high mortality largely due to poor drug exposure in infected lesions. To better understand the potential of IBX to treat such infections, we investigated its penetration at the site of infection. Using matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) and laser capture microdissection (LCM)-directed high-pressure liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), we investigated tissue distribution and lesion-specific drug exposure of IBX in a clinically relevant IAC mouse model. After a single-dose treatment, IBX quickly distributed into tissues and efficiently accumulated within lesions. Drug concentrations of IBX within the liver abscesses were almost 100-fold higher than the serum concentration. In addition, drug penetration after repeated treatment of IBX was compared with micafungin. IBX exhibited robust and long-lasting lesion penetration after repeated treatment. These data indicate that IBX penetrates into intra-abdominal abscesses highly efficiently and holds promise as a potential therapeutic option for IAC patients.