The differential virulence of Fusarium strains causing corneal infections and plant diseases is associated with accessory chromosome composition.

Fusarium oxysporum is a cross-kingdom pathogen. While some strains cause disseminated fusariosis and blinding corneal infections in humans, others are responsible for devastating vascular wilt diseases in plants. To better understand the distinct adaptations of F. oxysporum to animal or plant hosts, we conducted a comparative phenotypic and genetic analysis of two strains: MRL8996 (isolated from a keratitis patient) and Fol4287 (isolated from a wilted tomato [ Solanum lycopersicum ]). In vivo infection of mouse corneas and tomato plants revealed that, while both strains cause symptoms in both hosts, MRL8996 caused more severe corneal ulceration and perforation in mice, whereas Fol4287 induced more pronounced wilting symptoms in tomato. In vitro assays using abiotic stress treatments revealed that the human pathogen MRL8996 was better adapted to elevated temperatures, whereas the plant pathogen Fol4287 was more tolerant of osmotic and cell wall stresses. Both strains displayed broad resistance to antifungal treatment, with MRL8996 exhibiting the paradoxical effect of increased tolerance to higher concentrations of the antifungal caspofungin. We identified a set of accessory chromosomes (ACs) and protein-encoding genes with distinct transposon profiles and functions, respectively, between MRL8996 and Fol4287. Interestingly, ACs from both genomes also encode proteins with shared functions, such as chromatin remodeling and post-translational protein modifications. Our phenotypic assays and comparative genomics analyses lay the foundation for future studies correlating genotype with phenotype and for developing targeted antifungals for agricultural and clinical uses. Importance: Fusarium oxysporum is a cross-kingdom fungal pathogen that infects both plants and animals. In addition to causing many devastating wilt diseases, this group of organisms was recently recognized by the World Health Organization as a high-priority threat to human health. Climate change has increased the risk of Fusarium infections, as Fusarium strains are highly adaptable to changing environments. Deciphering fungal adaptation mechanisms is crucial to developing appropriate control strategies. We performed a comparative analysis of Fusarium strains using an animal (mouse) and plant (tomato) host and in vitro conditions that mimic abiotic stress. We also performed comparative genomics analyses to highlight the genetic differences between human and plant pathogens and correlate their phenotypic and genotypic variations. We uncovered important functional hubs shared by plant and human pathogens, such as chromatin modification, transcriptional regulation, and signal transduction, which could be used to identify novel antifungal targets.

Characteristics and prediction of agricultural ecological efficiency for coordination between economy and environment.

Agricultural ecological efficiency is an important tool with which to measure the coordination of the sustainable development of agricultural economies and ecological environments. In this paper, a super-efficiency slacks-based measures model was used to measure the agricultural ecological efficiency in Hebei Province. The characteristics of spatial and temporal evolution patterns were explored using a spatial Markov transfer matrix. The results showed that (i) based on measurements, the agricultural ecological efficiency in Hebei Province showed regional differences in four regions (eastern, northern, central and southern Hebei) and 141 counties; (ii) from the perspective of evolutionary characteristics of agricultural ecological efficiency, the overall development of in Hebei Province was good, with more concentrated spatial distribution and more obvious direction, while the type of transfer of agricultural ecological efficiency in Hebei Province showed strong stability that was significantly affected by geographical neighborhood conditions and the club convergence phenomenon; (iii) from the perspective of the long-term evolutionary trend of agricultural ecological efficiency, the areas adjacent to counties with low efficiency had limited potential for improvement, and the areas adjacent to counties with high grade had great potential. However, it was difficult to achieve large-scale improvement in agricultural ecological efficiency in Hebei Province, whether the impact of geospatial backgrounds was considered or not.

Dosimetric validation for prospective clinical trial on GRID collimator-based spatially fractionated radiation therapy: Dose metrics consistency and heterogeneous pattern reproducibility.

PURPOSE: The purpose of this study is to characterize the dosimetric properties of a commercial brass GRID collimator for high energy photon beams including 15 and 10 MV. Then, the difference in dosimetric parameters of GRID beams among different energies and linacs was evaluated. METHOD: A water tank scanning system was used to acquire the dosimetric parameters, including the percentage depth dose (PDD), beam profiles, peak to valley dose ratios (PVDRs), and output factors (OFs). The profiles at various depths were measured at 100 cm source to surface distance (SSD), and field sizes of 10 × 10 cm2 and 20 × 20 cm2 on three linacs. The PVDRs and OFs were measured and compared with the treatment planning system (TPS) calculations. RESULTS: Compared with the open beam data, there were noticeable changes in PDDs of GRID fields across all the energies. The GRID fields demonstrated a maximal of 3 mm shift in dmax (Truebeam STX, 15MV, 10 × 10 cm2). The PVDR decreased as beam energy increases. The difference in PVDRs between Trilogy and Truebeam STx using 6MV and 15MV was 1.5% ± 4.0% and 2.1% ± 4.3%, respectively. However, two Truebeam linacs demonstrated less than 2% difference in PVDRs. The OF of the GRID field was dependent on the energy and field size. The measured PDDs, PVDRs, and OFs agreed with the TPS calculations within 3% difference. The TPS calculations agreed with the measurements when using 1 mm calculation resolution. CONCLUSION: The dosimetric characteristics of high-energy GRID fields, especially PVDR, significantly differ from those of low-energy GRID fields. Two Truebeam machines are interchangeable for GRID therapy, while a pronounced difference was observed between Truebeam and Trilogy. A series of empirical equations and reference look-up tables for GRID therapy can be generated to facilitate clinical applications.

Entangled photon pair generation in an integrated SiC platform.

Entanglement plays a vital role in quantum information processing. Owing to its unique material properties, silicon carbide recently emerged as a promising candidate for the scalable implementation of advanced quantum information processing capabilities. To date, however, only entanglement of nuclear spins has been reported in silicon carbide, while an entangled photon source, whether it is based on bulk or chip-scale technologies, has remained elusive. Here, we report the demonstration of an entangled photon source in an integrated silicon carbide platform for the first time. Specifically, strongly correlated photon pairs are efficiently generated at the telecom C-band wavelength through implementing spontaneous four-wave mixing in a compact microring resonator in the 4H-silicon-carbide-on-insulator platform. The maximum coincidence-to-accidental ratio exceeds 600 at a pump power of 0.17 mW, corresponding to a pair generation rate of (9 ± 1) × 103 pairs/s. Energy-time entanglement is created and verified for such signal-idler photon pairs, with the two-photon interference fringes exhibiting a visibility larger than 99%. The heralded single-photon properties are also measured, with the heralded g(2)(0) on the order of 10-3, demonstrating the SiC platform as a prospective fully integrated, complementary metal-oxide-semiconductor compatible single-photon source for quantum applications.

Advancements and future directions in positron emission tomography-guided radiotherapy: a narrative review.

BACKGROUND AND OBJECTIVE: Positron emission tomography (PET) imaging has been useful in delineating tumor volumes and allowing for improved radiation treatment. The field of PET-guided radiotherapy is rapidly growing and will have significant impact on radiotherapy delivery in the future. This narrative review provides an overview of the current state of PET-guided radiotherapy as well as the future directions of the field. METHODS: For this narrative review, PubMed was searched for articles from 2010-2023. A total of 18 keywords or phrases were searched to provide an overview of PET-guided radiotherapy, radiotracers, the role of PET-guided radiotherapy in oligometastatic disease, and biology-guided radiotherapy (BgRT). The first 300 results for each keyword were searched and relevant articles were extracted. The references of these articles were also reviewed for relevant articles. KEY CONTENT AND FINDINGS: In radiotherapy, 18F-2-fluoro-2-deoxy-D-glucose (F-FDG or FDG) is the major radiotracer for PET and when combined with computed tomography (CT) scan allows for anatomic visualization of metabolically active malignancy. Novel radiotracers are being explored to delineate certain cell types and numerous tumor metrics including metabolism, hypoxia, vascularity, and cellular proliferation. This molecular and functional imaging will provide improved tumor characterization. Through these radiotracers, radiation plans can employ dose painting by creating different dose levels based upon specific risk factors of the target volume. Additionally, biologic imaging during radiotherapy can allow for adaptation of the radiation plan based on response to treatment. Dose painting and adaptive radiotherapy should improve the therapeutic ratio through more selective dose delivery. The novel PET-linear accelerator hopes to combine these techniques and more by using radiotracers to deliver BgRT. The areas of radiotracer uptake will serve as fiducials to guide radiotherapy to themselves. This technique may prove promising in the growing area of oligometastatic radiation treatment. CONCLUSIONS: Significant challenges exist for the future of PET-guided radiotherapy. However, with the advancements being made, PET imaging is set to change the delivery of radiotherapy.

Umbilical cord mesenchymal stem cell-derived exosomes inhibits fibrosis in human endometrial stromal cells via miR-140-3p/FOXP1/Smad axis.

Endometrial fibrosis is the histologic appearance of intrauterine adhesion (IUA). Emerging evidences demonstrated umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-exo) could alleviate endometrial fibrosis. But the specific mechanism is not clear. In this study, we explored the effect of UCMSC-exo on endometrial fibrosis, and investigated the possible role of miR-140-3p/FOXP1/Smad axis in anti-fibrotic properties of UCMSC-exo. UCMSC-exo were isolated and identified. Transforming growth factor-ß (TGF-ß) was used to induce human endometrial stromal cell (HESC) fibrosis. Dual luciferase assay was performed to verify the relationship between miR-140-3p and FOXP1. The expressions of fibrotic markers, SIP1, and p-Smad2/p-Smad3 in HESCs stimulated with UCMSC-exo were detected by western blot. In addition, the effects of miR-140-3p mimic, miR-140-3p inhibitor and FOXP1 over-expression on endometrial fibrosis were assessed. The isolated UCMSC-exo had a typical cup-shaped morphology and could be internalized into HESCs. The expressions of fibrotic markers were significantly increased by TGF-ß, which was reversed by UCMSC-exo. MiR-140-3p in UCMSC-exo ameliorated TGf-ß-induced HESCs fibrosis. FOXP1 was identified as the direct target of miR-140-3p, which could inversely regulate miR-140-3p's function on HESCs fibrosis. Furthermore, we demonstrated that miR-140-3p in UCMSC-exo regulated Smad signal pathway to exert the anti-fibrotic effect in HESCs. The anti-fibrotic effect of UCMSC-derived exosomes against HESC fibrosis was at least partially achieved by miR-140-3p/FOXP1/Smad axis.

Lycium barbarum polysaccharide reverses drug resistance in oxaliplatin-resistant colon cancer cells by inhibiting PI3K/AKT-dependent phosphomannose isomerase.

Objective: Here, we aimed to explore the effect of LBP in combination with Oxaliplatin (OXA) on reversing drug resistance in colon cancer cells through in vitro and in vivo experiments. We also aimed to explore the possible mechanism underlying this effect. Finally, we aimed to determine potential targets of Lycium barbarum polysaccharide (LBP) in colon cancer (CC) through network pharmacology and molecular docking. Methods: The invasion ability of colon cancer cells was assessed using the invasion assay. The migration ability of these cells was assessed using the migration assay and wound healing assay. Cell cycle analysis was carried out using flow cytometry. The expression levels of phosphomannose isomerase (PMI) and ATP-binding cassette transport protein of G2 (ABCG2) proteins were determined using immunofluorescence and western blotting. The expression levels of phosphatidylinositol3-kinase (PI3K), protein kinase B (AKT), B-cell lymphoma 2 (Bcl-2), and BCL2-Associated X (Bax) were determined using western blotting. Forty BALB/c nude mice purchased from Weitong Lihua, Beijing, for the in vivo analyses. The mice were randomly divided into eight groups. They were administered HCT116 and HCT116-OXR cells to prepare colon cancer xenograft models and then treated with PBS, LBP (50 mg/kg), OXA (10 mg/kg), or LBP + OXA (50 mg/kg + 10 mg/kg). The tumor weight and volume of treated model mice were measured, and organ toxicity was evaluated using hematoxylin and eosin staining. The expression levels of PMI, ABCG2, PI3K, and AKT proteins were then assessed using immunohistochemistry. Moreover, PMI and ABCG2 expression levels were analyzed using immunofluorescence and western blotting. The active components and possible targets of LBP in colon cancer were explored using in silico analysis. GeneCards was used to identify CC targets, and an online Venn analysis tool was used to determine intersection targets between these and LBP active components. The PPI network for intersection target protein interactions and the PPI network for interactions between the intersection target proteins and PMI was built using STRING and Cytoscape. To obtain putative targets of LBP in CC, we performed GO function enrichment and KEGG pathway enrichment analyses. Results: Compared with the HCT116-OXR blank treatment group, both invasion and migration abilities of HCT116-OXR cells were inhibited in the LBP + OXA (2.5 mg/mL LBP, 10 µΜ OXA) group (p < 0.05). Cells in the LBP + OXA (2.5 mg/mL LBP, 10 µΜ OXA) group were found to arrest in the G1 phase of the cell cycle. Knockdown of PMI was found to downregulate PI3K, AKT, and Bcl-2 (p < 0.05), while it was found to upregulate Bax (p < 0.05). After treatment with L. barbarum polysaccharide, 40 colon cancer subcutaneous tumor models showed a decrease in tumor size. There was no difference in the liver index after LBP treatment (p > 0.05). However, the spleen index decreased in the OXA and LBP + OXA groups (p < 0.05), possibly as a side effect of oxaliplatin. Immunohistochemistry, immunofluorescence, and western blotting showed that LBP + OXA treatment decreased PMI and ABCG2 expression levels (p < 0.05). Moreover, immunohistochemistry showed that LBP + OXA treatment decreased the expression levels of PI3K and AKT (p < 0.05). Network pharmacology analysis revealed 45 active LBP components, including carotenoids, phenylpropanoids, quercetin, xanthophylls, and other polyphenols. It also revealed 146 therapeutic targets of LBP, including AKT, SRC, EGFR, HRAS, STAT3, and MAPK3. KEGG pathway enrichment analysis showed that the LBP target proteins were enriched in pathways, including cancer-related signaling pathways, PI3K/AKT signaling pathway, and IL-17 signaling pathways. Finally, molecular docking experiments revealed that the active LBP components bind well with ABCG2 and PMI. conclusion: Our in vitro experiments showed that PMI knockdown downregulated PI3K, AKT, and Bcl-2 and upregulated Bax. This finding confirms that PMI plays a role in drug resistance by regulating the PI3K/AKT pathway and lays a foundation to study the mechanism underlying the reversal of colon cancer cell drug resistance by the combination of LBP and OXA. Our in vivo experiments showed that LBP combined with oxaliplatin could inhibit tumor growth. LBP showed no hepatic or splenic toxicity. LBP combined with oxaliplatin could downregulate the expression levels of PMI, ABCG2, PI3K, and AKT; it may thus have positive significance for the treatment of advanced metastatic colon cancer. Our network pharmacology analysis revealed the core targets of LBP in the treatment of CC as well as the pathways they are enriched in. It further verified the results of our in vitro and in vivo experiments, showing the involvement of multi-component, multi-target, and multi-pathway synergism in the drug-reversing effect of LBP in CC. Overall, the findings of the present study provide new avenues for the future clinical treatment of CC.

Implementation of Learning Management Systems (LMS) in higher education systems through bipolar complex hesitant fuzzy Aczel-Alsina power aggregation operators: A case review for China.

A learning management system (LMS) is a web-based application or software platform computed to facilitate the development, tracking, management, reporting, and delivery of education and training programs. Many valuable and dominant factors are working behind the Learning Management System (LMS), but no one can find which factor is most important and valuable for LMS during COVID-19 among the following five alternatives, called Improved Accessibility, Blended Learning, Collaboration and Communications, Assessment and Evaluation, and Administrative Efficiency. For this, first, we derive the techniques of bipolar complex hesitant fuzzy (BCHF) sets, and then we evaluate some flexible operational laws, called Algebraic operational laws and Aczel-Alsina operational laws. Secondly, using the above techniques, we elaborate the technique of BCHF Aczel-Alsina power averaging (BCHFAAPA), BCHF Aczel-Alsina power weighted averaging (BCHFAAPWA), BCHF Aczel-Alsina power geometric (BCHFAAPG), and BCHF Aczel-Alsina power weighted geometric (BCHFAAPWG) operators. Some basic properties are also investigated for each proposed operator. Further, to evaluate the problem concerning LMS, we compute the multi-attribute decision-making (MADM) techniques for invented operators. Finally, we select some prevailing operators and try to compare their ranking results with our proposed results to enhance the worth and capability of the invented theory.

Intravenous immunoglobulin alleviates Japanese encephalitis virus-induced peripheral neuropathy by inhibiting the ASM/ceramide pathway.

Japanese encephalitis virus (JEV) infection is considered a global public health emergency. Severe peripheral neuropathy caused by JEV infection has increased disability and mortality rates in recent years. Because there are very few therapeutic options for JEV infection, prompt investigations of the ability of clinically safe, efficacious and globally available drugs to inhibit JEV infection and ameliorate peripheral neuropathy are urgently needed. In this study, we found that high doses of intravenous immunoglobulin, a function inhibitor of acid sphingomyelinase (FIASMA), inhibited acid sphingomyelinase (ASM) and ceramide activity in the serum and sciatic nerve of JEV-infected rats, reduced disease severity, reversed electrophysiological and histological abnormalities, significantly reduced circulating proinflammatory cytokine levels, inhibited Th1 and Th17 cell proliferation, and suppressed the infiltration of inflammatory CD4 + cells into the sciatic nerve. It also maintained the peripheral nerve-blood barrier without causing severe clinical side effects. In terms of the potential mechanisms, ASM was found to participate in immune cell differentiation and to activate immune cells, thereby exerting proinflammatory effects. Therefore, immunoglobulin is a FIASMA that reduces abnormal immune responses and thus targets the ASM/ceramide system to treat peripheral neuropathy caused by JEV infection.

A self-aligned assembling terahertz metasurface microfluidic sensor for liquid detection.

This paper reports a new terahertz metasurface microfluidic sensor, which is actually a kind of reflective terahertz metasurface absorber with a microfluidic-channel structure located in the strong field energy region of the absorber. The metasurface structure is made on an ultra-thin quartz substrate as the cap layer, while a two-step structure is made on a silicon substrate as the pedestal layer. In order to precisely control the thickness of the microfluidic channel, the cap layer is self-aligned assembled with the pedestal layer to form the terahertz metasurface microfluidic sensor. The obtained sensor could enhance the light-matter interaction, resulting in high sensing performance. The measured results show that the sensor has a perfect absorption peak at 2.60 THz and a high Q-factor of 62.59, which are basically consistent with the simulated results. The sensitivity and FOM calculated based on the measured results of different liquids with different refractive indices is 0.733 THz per RIU and 16.4, respectively. Compared with some recently related work, the sensitivity is increased by about 40%, the Q-factor is increased by 3-5 times, and the FOM is increased by 5 times, which make the sensor have great application potential for solution detection in the terahertz frequency band.

Topotactic Conversion of Titanium-Oxo Clusters to a Stable TOC-Based Metal-Organic Framework with the Selective Adsorption of Cationic Dyes.

Titanium-oxo cluster (TOC)-based metal-organic frameworks (MOFs) have received considerable attention in recent years due to their ability to expand the application of TOCs to fields that require highly stable frameworks. Herein, a new cyclic TOC formulated as [Ti6O6(OiPr)8(TTFTC)(phen)2]2 (1, where TTFTC = tetrathiafulvalene tetracarboxylate and phen = phenanthroline) was crystallographically characterized. TOC 1 takes a rectangular ring structure with two phen-modified Ti6 clusters as the width and two TTFTC ligands as the length. An intracluster ligand-to-ligand (TTF-to-phen) charge transfer in 1 was found for TOCs for the first time. Compound 1 undergoes topotactic conversion to generate stable TOC-MOF P1, in which the rectangular framework in 1 formed by a TOC core and ligands is retained, as verified by comprehensive characterization. P1 shows an efficient and rapid selective adsorption capacity for cationic dyes. The experimental adsorption capacity (qex) of P1 reaches a value of up to 789.2 mg/g at 298 K for the crystal violet dye, which is the highest among those of various adsorbents. The calculated models are first used to reveal the structure-property relationship of the cyclic host to different guest dyes. The results further confirmed the host MOF structure of P1.

Primary Care Asthma Attack Prediction Models for Adults: A Systematic Review of Reported Methodologies and Outcomes.

Prognostic models hold great potential for predicting asthma exacerbations, providing opportunities for early intervention, and are a popular area of current research. However, it is unclear how models should be compared and contrasted, given their differences in both design and performance, particularly with a view to potential implementation in routine practice. This systematic review aimed to identify novel predictive models of asthma attacks in adults and compare differences in construction related to populations, outcome definitions, prediction time horizons, algorithms, validation, and performance estimation. Twenty-five studies were identified for comparison, with varying definitions of asthma attacks and prediction event time horizons ranging from 15 days to 30 months. The most commonly used algorithm was logistic regression (20/25 studies); however, none of the six which tested multiple algorithms identified it as highest performing algorithm. The effect of various study design characteristics on performance was evaluated in order to provide context to the limitations of highly performing models. Models used a variety of constructs, which affected both their performance and their viability for implementation in routine practice. Consultation with stakeholders is necessary to identify priorities for model refinement and to create a benchmark of acceptable performance for implementation in clinical practice.

Identification of Pancreatic Metastasis Cells and Cell Spheroids by the Organelle-Targeting Sensor Array.

Pancreatic cancer is a highly malignant and metastatic cancer. Pancreatic cancer can lead to liver metastases, gallbladder metastases, and duodenum metastases. The identification of pancreatic cancer cells is essential for the diagnosis of metastatic cancer and exploration of carcinoma in situ. Organelles play an important role in maintaining the function of cells, the various cells show significant differences in organelle microenvironment. Herein, six probes are synthesized for targeting mitochondria, lysosomes, cell membranes, endoplasmic reticulum, Golgi apparatus, and lipid droplets. The six fluorescent probes form an organelles-targeted sensor array (OT-SA) to image pancreatic metastatic cancer cells and cell spheroids. The homology of metastatic cancer cells brings the challenge for identification of these cells. The residual network (ResNet) model has been proven to automatically extract and select image features, which can figure out a subtle difference among similar samples. Hence, OT-SA is developed to identify pancreatic metastasis cells and cell spheroids in combination with ResNet analysis. The identification accuracy for the pancreatic metastasis cells (> 99%) and pancreatic metastasis cell spheroids (> 99%) in the test set is successfully achieved respectively. The organelles-targeting sensor array provides a method for the identification of pancreatic cancer metastasis in cells and cell spheroids.

Kynurenine 3-monooxygenase limits de novo NAD+ synthesis through dietary tryptophan in renal proximal tubule epithelial cell models.

Nicotinamide adenine dinucleotide (NAD+) is a pivotal coenzyme, essential for cellular reactions, metabolism, and mitochondrial function. Depletion of kidney NAD+ levels and reduced de novo NAD+ synthesis through the tryptophan-kynurenine pathway are linked to acute kidney injury (AKI), whereas augmenting NAD+ shows promise in reducing AKI. We investigated de novo NAD+ biosynthesis using in vitro, ex vivo, and in vivo models to understand its role in AKI. Two-dimensional (2-D) cultures of human primary renal proximal tubule epithelial cells (RPTECs) and HK-2 cells showed limited de novo NAD+ synthesis, likely due to low pathway enzyme gene expression. Using three-dimensional (3-D) spheroid culture model improved the expression of tubular-specific markers and enzymes involved in de novo NAD+ synthesis. However, de novo NAD+ synthesis remained elusive in the 3-D spheroid culture, regardless of injury conditions. Further investigation revealed that 3-D cultured cells could not metabolize tryptophan (Trp) beyond kynurenine (KYN). Intriguingly, supplementation of 3-hydroxyanthranilic acid into RPTEC spheroids was readily incorporated into NAD+. In a human precision-cut kidney slice (PCKS) ex vivo model, de novo NAD+ synthesis was limited due to substantially downregulated kynurenine 3-monooxygenase (KMO), which is responsible for KYN to 3-hydroxykynurenine conversion. KMO overexpression in RPTEC 3-D spheroids successfully reinstated de novo NAD+ synthesis from Trp. In addition, in vivo study demonstrated that de novo NAD+ synthesis is intact in the kidney of the healthy adult mice. Our findings highlight disrupted tryptophan-kynurenine NAD+ synthesis in in vitro cellular models and an ex vivo kidney model, primarily attributed to KMO downregulation.NEW & NOTEWORTHY Nicotinamide adenine dinucleotide (NAD+) is essential in regulating mitochondrial function. Reduced NAD+ synthesis through the de novo pathway is associated with acute kidney injury (AKI). Our study reveals a disruption in de novo NAD+ synthesis in proximal tubular models, but not in vivo, attributed to downregulation of enzyme kynurenine 3-monooxygenase (KMO). These findings highlight a crucial role of KMO in governing de novo NAD+ biosynthesis within the kidney, shedding light on potential AKI interventions.

Longitudinal intravital imaging of mouse placenta.

Studying placental functions is crucial for understanding pregnancy complications. However, imaging placenta is challenging due to its depth, volume, and motion distortions. In this study, we have developed an implantable placenta window in mice that enables high-resolution photoacoustic and fluorescence imaging of placental development throughout the pregnancy. The placenta window exhibits excellent transparency for light and sound. By combining the placenta window with ultrafast functional photoacoustic microscopy, we were able to investigate the placental development during the entire mouse pregnancy, providing unprecedented spatiotemporal details. Consequently, we examined the acute responses of the placenta to alcohol consumption and cardiac arrest, as well as chronic abnormalities in an inflammation model. We have also observed viral gene delivery at the single-cell level and chemical diffusion through the placenta by using fluorescence imaging. Our results demonstrate that intravital imaging through the placenta window can be a powerful tool for studying placenta functions and understanding the placental origins of adverse pregnancy outcomes.

Multi-omics Analyses Identify AKR1A1 as a Biomarker for Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. As many genes associate with DKD, multi-omics approaches were employed to narrow the list of functional genes, gene products and related pathways providing insights into the pathophysiological mechanisms of DKD. The Kidney Precision Medicine Project human kidney single-cell RNA-sequencing (scRNAseq) dataset and Mendeley Data on human kidney cortex biopsy proteomics were utilized. R package Seurat was used to analyze scRNAseq and subset proximal tubule cells. PathfindR was applied for pathway analysis in cell type-specific differentially expressed genes and R limma package was used to analyze differential protein expression in kidney cortex. A total of 790 differentially expressed genes were identified in proximal tubule cells, including 530 upregulated and 260 downregulated transcripts. Compared with differentially expressed proteins, 24 genes/proteins were in common. An integrated analysis combining protein quantitative trait loci (pQTL), GWAS hits (estimated glomerular filtration rate) and a plasma metabolomics analysis was performed using baseline metabolites predictive of DKD progression in our longitudinal Diabetes Heart Study samples. Aldo-keto reductase family 1 member A1 gene (AKR1A1) was revealed as a potential molecular hub for DKD cellular dysfunction in several cross-linked pathways featured by deficiency of this enzyme.

Rapid and Repeated Climate Adaptation Involving Chromosome Inversions following Invasion of an Insect.

Following invasion, insects can become adapted to conditions experienced in their invasive range, but there are few studies on the speed of adaptation and its genomic basis. Here, we examine a small insect pest, Thrips palmi, following its contemporary range expansion across a sharp climate gradient from the subtropics to temperate areas. We first found a geographically associated population genetic structure and inferred a stepping-stone dispersal pattern in this pest from the open fields of southern China to greenhouse environments of northern regions, with limited gene flow after colonization. In common garden experiments, both the field and greenhouse groups exhibited clinal patterns in thermal tolerance as measured by critical thermal maximum (CTmax) closely linked with latitude and temperature variables. A selection experiment reinforced the evolutionary potential of CTmax with an estimated h2 of 6.8% for the trait. We identified 3 inversions in the genome that were closely associated with CTmax, accounting for 49.9%, 19.6%, and 8.6% of the variance in CTmax among populations. Other genomic variations in CTmax outside the inversion region were specific to certain populations but functionally conserved. These findings highlight rapid adaptation to CTmax in both open field and greenhouse populations and reiterate the importance of inversions behaving as large-effect alleles in climate adaptation.

Deletion, but not heterozygosity, of eNOS raises blood pressure and aggravates nephropathy in BTBR ob/ob mice.

INTRODUCTION: ob/ob mice are a leptin-deficient type 2 diabetes mellitus model, which, on a BTBR background, mimics glomerular pathophysiology of diabetic nephropathy (DN). Since leptin deficiency reduces blood pressure (BP), and endothelial nitric oxide synthase (eNOS) lowers BP and is kidney protective, we attempted to develop a more robust DN model by introducing eNOS deficiency in BTBR ob/ob mice. METHODS: Six experimental groups included littermate male and female BTBR ob/ob or wild-type for ob (control) as well as wild-type (WT), heterozygote (HET) or knockout (KO) for eNOS. Systolic BP (by automated tail-cuff) and GFR (by FITC sinistrin plasma kinetics) were determined in awake mice at 27-30 weeks of age followed by molecular and histological kidney analyses. RESULTS: Male and female ob/ob WT presented hyperglycemia and larger body and kidney weight, GFR, glomerular injury, and urine albumin to creatinine ratio (UACR) despite modestly lower BP vs control WT. These effects were associated with higher tubular injury score and renal mRNA expression of NGAL only in males, whereas female ob/ob WT unexpectedly had lower KIM-1 and COL1A1 expression vs control WT, indicating sex differences. HET for eNOS did not consistently alter BP or renal outcome in control or ob/ob. In comparison, eNOS KO increased BP (15-25 mmHg) and worsened renal markers of injury, inflammation and fibrosis, GFR, UACR, and survival rates, as observed in control and, more pronounced, in ob/ob mice and independent of sex. CONCLUSIONS: Deletion, but not heterozygosity, of eNOS raises blood pressure and aggravates nephropathy in BTBR ob/ob mice.

The complete mitochondrial genome of Aphidius colemani (Hymenoptera: Braconidae: Aphidiinae).

The genome-level features are crucial genetic resources for species identification and phylogenetic analysis. Here, the complete mitochondrial genome of Aphidius colemani Viereck 1912 (Hymenoptera: Braconidae: Aphidiinae) was sequenced, determined and analyzed. The circular genome is 16,372 bp in length with an overall base composition of 38.9% for A, 46.2% for T, 6.7% for C, and 8.2% for G. The mitochondrial genome of A. colemani contained 13 protein-coding genes that initiated by the ATN codon, 22 transfer RNA genes, two ribosomal RNA genes (rRNAs), and a control region (CR). It shared the same gene arrangement patterns that occurred in two tRNA clusters of trnI-trnQ-trnM and trnW-trnC-trnY with Aphidius gifuensis. Phylogenetic analyses using Bayesian inference and Maximum-likelihood methods supported that the two species of Aphidiinae formed a clade and sister to other subfamilies of Braconidae.