VARIDT 3.0: the phenotypic and regulatory variability of drug transporter.

The phenotypic and regulatory variability of drug transporter (DT) are vital for the understanding of drug responses, drug-drug interactions, multidrug resistances, and so on. The ADME property of a drug is collectively determined by multiple types of variability, such as: microbiota influence (MBI), transcriptional regulation (TSR), epigenetics regulation (EGR), exogenous modulation (EGM) and post-translational modification (PTM). However, no database has yet been available to comprehensively describe these valuable variabilities of DTs. In this study, a major update of VARIDT was therefore conducted, which gave 2072 MBIs, 10 610 TSRs, 46 748 EGRs, 12 209 EGMs and 10 255 PTMs. These variability data were closely related to the transportation of 585 approved and 301 clinical trial drugs for treating 572 diseases. Moreover, the majority of the DTs in this database were found with multiple variabilities, which allowed a collective consideration in determining the ADME properties of a drug. All in all, VARIDT 3.0 is expected to be a popular data repository that could become an essential complement to existing pharmaceutical databases, and is freely accessible without any login requirement at: https://idrblab.org/varidt/.

M1AP interacts with the mammalian ZZS complex and promotes male meiotic recombination.

Following meiotic recombination, each pair of homologous chromosomes acquires at least one crossover, which ensures accurate chromosome segregation and allows reciprocal exchange of genetic information. Recombination failure often leads to meiotic arrest, impairing fertility, but the molecular basis of recombination remains elusive. Here, we report a homozygous M1AP splicing mutation (c.1074 + 2T > C) in patients with severe oligozoospermia owing to meiotic metaphase I arrest. The mutation abolishes M1AP foci on the chromosome axes, resulting in decreased recombination intermediates and crossovers in male mouse models. M1AP interacts with the mammalian ZZS (an acronym for yeast proteins Zip2-Zip4-Spo16) complex components, SHOC1, TEX11, and SPO16. M1AP localizes to chromosomal axes in a SPO16-dependent manner and colocalizes with TEX11. Ablation of M1AP does not alter SHOC1 localization but reduces the recruitment of TEX11 to recombination intermediates. M1AP shows cytoplasmic localization in fetal oocytes and is dispensable for fertility and crossover formation in female mice. Our study provides the first evidence that M1AP acts as a copartner of the ZZS complex to promote crossover formation and meiotic progression in males.

Tumor suppressor PALB2 maintains redox and mitochondrial homeostasis in the brain and cooperates with ATG7/autophagy to suppress neurodegeneration.

The PALB2 tumor suppressor plays key roles in DNA repair and has been implicated in redox homeostasis. Autophagy maintains mitochondrial quality, mitigates oxidative stress and suppresses neurodegeneration. Here we show that Palb2 deletion in the mouse brain leads to mild motor deficits and that co-deletion of Palb2 with the essential autophagy gene Atg7 accelerates and exacerbates neurodegeneration induced by ATG7 loss. Palb2 deletion leads to elevated DNA damage, oxidative stress and mitochondrial markers, especially in Purkinje cells, and co-deletion of Palb2 and Atg7 results in accelerated Purkinje cell loss. Further analyses suggest that the accelerated Purkinje cell loss and severe neurodegeneration in the double deletion mice are due to excessive oxidative stress and mitochondrial dysfunction, rather than DNA damage, and partially dependent on p53 activity. Our studies uncover a role of PALB2 in mitochondrial homeostasis and a cooperation between PALB2 and ATG7/autophagy in maintaining redox and mitochondrial homeostasis essential for neuronal survival.

Machine learning-derived identification of prognostic signature for improving prognosis and drug response in patients with ovarian cancer.

Clinical assessments relying on pathology classification demonstrate limited effectiveness in predicting clinical outcomes and providing optimal treatment for patients with ovarian cancer (OV). Consequently, there is an urgent requirement for an ideal biomarker to facilitate precision medicine. To address this issue, we selected 15 multicentre cohorts, comprising 12 OV cohorts and 3 immunotherapy cohorts. Initially, we identified a set of robust prognostic risk genes using data from the 12 OV cohorts. Subsequently, we employed a consensus cluster analysis to identify distinct clusters based on the expression profiles of the risk genes. Finally, a machine learning-derived prognostic signature (MLDPS) was developed based on differentially expressed genes and univariate Cox regression genes between the clusters by using 10 machine-learning algorithms (101 combinations). Patients with high MLDPS had unfavourable survival rates and have good prediction performance in all cohorts and in-house cohorts. The MLDPS exhibited robust and dramatically superior capability than 21 published signatures. Of note, low MLDIS have a positive prognostic impact on patients treated with anti-PD-1 immunotherapy by driving changes in the level of infiltration of immune cells. Additionally, patients suffering from OV with low MLDIS were more sensitive to immunotherapy. Meanwhile, patients with low MLDIS might benefit from chemotherapy, and 19 compounds that may be potential agents for patients with low MLDIS were identified. MLDIS presents an appealing instrument for the identification of patients at high/low risk. This could enhance the precision treatment, ultimately guiding the clinical management of OV.

Cornichon protein CNIH4 is not essential for mice gametogenesis and fertility.

BACKGROUND: Cornichon is a functionally conserved transmembrane protein family that generally acts as a cargo-sorting receptor and cycles between the ER and the Golgi. Four Cornichon family members (CNIH1-4) have been identified. The key residues responsible for CNIH1-3 to bind to AMPA receptors are not conserved in CNIH4. Additionally, the function of CNIH1-3 in GPCR signaling is less established, while more established in case of CNIH4 protein that interact with GPCR and control their exportation. Many GPCRs are known for their essential roles in male and female gonad development. But whether CNIH4 plays a role in gametogenesis remains unknown. DESIGN: Mice carrying the Cnih4 knockout allele (Cnih4tm1a-/-) were generated by insertion of a LacZ reporter and a polyadenylation site after exon 1. Western blot, Immunofluorescence, computer-aided sperm analysis and other methods were used in the functional analysis. RESULTS: We identified that both Cnih4tm1a-/- male and female mice have normal fertility. Though, the sperm count, morphology, and motility of Cnih4tm1a-/- mice were slightly impaired compared to those of wild-type mice, the testes to body weight ratio and testicular histology were similar to those in control mice. Histological examination of Cnih4tm1a-/- ovaries detected follicles from primordial to antral stages and the numbers of follicles at each stage were also comparable to wild-type controls. Normal fertility was noticed after six-month fertility tests. That was likely due to the compensatory role of Chin3, which significantly upregulated in the Cnih4tm1a-/- mice to preserve the fertility role. CONCLUSION: Despite CNIH4 showing enriched expression in mouse germ cells, our genetic knockout studies demonstrated that CNIH4 is not essential for gametogenesis and fertility in mice although with a slight reduction in count, motility and morphology of sperm in male mice.

Differential alternative polyadenylation of homoeologous genes of allohexaploid wheat ABD subgenomes during drought stress response.

Because allohexaploid wheat genome contains ABD subgenomes, how the expression of homoeologous genes is coordinated remains largely unknown, particularly at the co-transcriptional level. Alternative polyadenylation (APA) is an important part of co-transcriptional regulation, which is crucial in developmental processes and stress responses. Drought stress is a major threat to the stable yield of wheat. Focusing on APA, we used poly(A) tag sequencing to track poly(A) site dynamics in wheat under drought stress. The results showed that drought stress led to extensive APA involving 37-47% of differentially expressed genes in wheat. Significant poly(A) site switching was found in stress-responsive genes. Interestingly, homoeologous genes exhibit unequal numbers of poly(A) sites, divergent APA patterns with tissue specificity and time-course dynamics, and distinct 3'-UTR length changes. Moreover, differentially expressed transcripts in leaves and roots used different poly(A) signals, the up- and downregulated isoforms had distinct preferences for non-canonical poly(A) sites. Genes that encode key polyadenylation factors showed differential expression patterns under drought stress. In summary, poly(A) signals and the changes in core poly(A) factors may widely affect the selection of poly(A) sites and gene expression levels during the response to drought stress, and divergent APA patterns among homoeologous genes add extensive plasticity to this responsive network. These results not only reveal the significant role of APA in drought stress response, but also provide a fresh perspective on how homoeologous genes contribute to adaptability through transcriptome diversity. In addition, this work provides information about the ends of transcripts for a better annotation of the wheat genome.

Double-Model Decay Strategy Integrating Persistent Photogenic Radicaloids with Dynamic Circularly Polarized Doublet Radiance and Triplet Afterglow.

Organic phosphors integrating circularly polarized persistent luminescence (CPPL) across the visible range are widespread for applications in optical information encryption, bioimaging, and 3D display, but the pursuit of color-tunable CPPL in single-component organics remains a formidable task. Herein, via in situ photoimplanting radical ion pairing into axial chiral crystals, we present and elucidate an unprecedented double-module decay strategy to achieve a colorful CPPL through a combination of stable triplet emission from neutral diphosphine and doublet radiance from photogenic radicals in an exclusive crystalline framework. Owing to the photoactivation-dependent doublet radiance component and an inherent triplet phosphorescence in the asymmetric environment, the CPL vision can be regulated by altering the photoactivation and observation time window, allowing colorful glow tuning from blue and orange to delayed green emission. Mechanism studies clearly reveal that this asymmetric electron migration environment and hybrid n-π* and π-π* instincts are responsible for the afterglow and radical radiance at ambient conditions. Moreover, we demonstrate the applications of colorful CPPL for displays and encryption via manipulation of both excitation and observation times.

Homozygous mutations in C14orf39/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans.

Human infertility is a multifactorial disease that affects 8%-12% of reproductive-aged couples worldwide. However, the genetic causes of human infertility are still poorly understood. Synaptonemal complex (SC) is a conserved tripartite structure that holds homologous chromosomes together and plays an indispensable role in the meiotic progression. Here, we identified three homozygous mutations in the SC coding gene C14orf39/SIX6OS1 in infertile individuals from different ethnic populations by whole-exome sequencing (WES). These mutations include a frameshift mutation (c.204_205del [p.His68Glnfs∗2]) from a consanguineous Pakistani family with two males suffering from non-obstructive azoospermia (NOA) and one female diagnosed with premature ovarian insufficiency (POI) as well as a nonsense mutation (c.958G>T [p.Glu320∗]) and a splicing mutation (c.1180-3C>G) in two unrelated Chinese men (individual P3907 and individual P6032, respectively) with meiotic arrest. Mutations in C14orf39 resulted in truncated proteins that retained SYCE1 binding but exhibited impaired polycomplex formation between C14ORF39 and SYCE1. Further cytological analyses of meiosis in germ cells revealed that the affected familial males with the C14orf39 frameshift mutation displayed complete asynapsis between homologous chromosomes, while the affected Chinese men carrying the nonsense or splicing mutation showed incomplete synapsis. The phenotypes of NOA and POI in affected individuals were well recapitulated by Six6os1 mutant mice carrying an analogous mutation. Collectively, our findings in humans and mice highlight the conserved role of C14ORF39/SIX6OS1 in SC assembly and indicate that the homozygous mutations in C14orf39/SIX6OS1 described here are responsible for infertility of these affected individuals, thus expanding our understanding of the genetic basis of human infertility.

Two-phase Porous Media Flow Model Based on the Incompressible Navier-Stokes Equation.

Two-phase porous media flow is important in many applications from drug delivery to groundwater diffusion and oil recovery and is of particular interest to biomedical diagnostic test developers using cellulose and nitrocellulose membranes with limited fluid sample volumes. This work presents a new two-phase porous media flow model based on the incompressible Navier-Stokes equation. The model aims to address the limitations of existing methods by incorporating a partial saturation distribution in porous media to account for limited fluid volumes. The basic parameters of the model are the pore size distribution and the contact angle. To validate the model, we solved five analytical solutions and compared them to corresponding experimental data. The experimentally measured penetration length data agreed with the model predictions, demonstrating model accuracy. Our findings suggest that this new two-phase porous media flow model can provide a valuable tool for researchers developing fluidic assays in paper and other porous media.

Biomolecular Interaction Analysis Quantification with a Low-Volume Microfluidic Chip and Particle Diffusometry.

Microfluidic techniques are widely applied in biomolecular analysis and disease diagnostic assays. While the volume of the sample that is directly used in such assays is often only femto-to microliters, the "dead volume" of solutions supplied in syringes and tubing can be much larger, even up to milliliters, increasing overall reagent use and making analysis significantly more expensive. To reduce the difficulty and cost, we designed a new chip using a low volume solution for analysis and applied it to obtain real-time data for protein-protein interaction measurements. The chip takes advantage of air/aqueous two-phase droplet flow, on-chip rapid mixing within milliseconds, and a droplet capture method, that ultimately requires only 2 µL of reagent solution. The interaction is analyzed by particle diffusometry, a nonintrusive and precise optical detection method to analyze the properties of microparticle diffusion in solution. Herein, we demonstrate on-chip characterization of human immunodeficiency virus p24 antibody-antigen protein binding kinetics imaged via fluorescence microscopy and analyzed by PD. The measured kon and koff are 1 × 106 M-1 s-1 and 3.3 × 10-4 s-1, respectively, and agree with independent measurement via biolayer interferometry and previously calculated p24-antibody binding kinetics. This new microfluidic chip and the protein-protein interaction analysis method can also be applied in other fields that require low-volume solutions to perform accurate measurement, analysis, and detection.

Enhanced Aggregation-Induced Delayed Electrochemiluminescence Triggered by Spatial Perturbation of Organic Dots.

Development of highly efficient, heavy-metal-free electrochemiluminescence (ECL) materials is attractive but still challenging. Herein, we report an aggregation-induced delayed ECL (AIDECL) active organic dot (OD) composed of a tert-butoxy-group-substituted benzophenone-dimethylacridine compound, which shows high ECL efficiency. The resultant ODs exhibit 2.1-fold higher ECL efficiency compared to control AIDECL-active ODs. Molecular stacking combined with theoretical calculations suggests that tert-butoxy groups effectively participate in the intermolecular interactions, further inhibiting the molecular motions in the aggregated states and thus accelerating radiative decay. On the basis of these ODs exhibiting excellent ECL performance, a proof-of-concept biosensor is constructed for the detection of miR-16 associated with Alzheimer's disease, which demonstrates excellent detection ability with the limit of detection of 1.7 fM. This work provides a new approach to improve the ECL efficiency and enriches the fundamental understanding of the structure-property relationship.

Lysophosphatidic acid promotes ESCC progression by increasing the level of CCL2 secreted by esophageal epithelial cells.

BACKGROUND: Lysophosphatidic acid (LPA) is a small bioactive lipid which acts as a potent regulator in various tumor progressions through six G-protein-coupled receptors (LPA1-LPA6). Our previous study demonstrated that the LPA-producing enzyme, autotaxin (ATX), was upregulated in esophageal squamous cell carcinoma (ESCC) and ATX high expression levels indicated a poor prognosis. Esophageal squamous cell carcinoma is a type of malignant tumor which originates from epithelial cells. Its progression can be affected by the interaction between cancer cells and normal cells. However, the impact of LPA on the interaction between esophageal epithelial cells and cancer cells in the development of ESCC remains uncertain. METHODS: MTS and Edu assays were performed to determine ESCC cell proliferation in culture medium (CM) derived from LPA-stimulated esophageal epithelial cells (Het-1a). A wound healing assay, transwell migration and an invasion assay were performed to assess the metastatic ability of ESCC cells. Cytokine array analysis was conducted to detect the differentially secreted cytokines in CM. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to uncover the pathways and cytokines that are influenced by LPA in ESCC. Immunohistochemical staining was employed to measure the expression of ATX and CCL2 in early-stage ESCC. Quantitative real-time PCR, western blot, enzyme-linked immunosorbent assay and an antibody neutralization assay were employed to measure the mechanism of LPA-mediated communication between epithelial cells and cancer cells. RESULTS: Functional experiments showed that exposing ESCC cancer cells to CM from LPA-treated Het-1a results in promoting proliferation, migration, invasion and epithelial-mesenchymal transition processes. Using cytokine array analysis, we discovered that LPA triggers the release of multiple cytokines from epithelial cells. After screening of the TCGA and GEO databases, CCL2 was identified and found to be correlated with ATX expression in ESCC. Furthermore, CCL2 levels in both mRNA expression and secretion were observed to be upregulated in epithelial cells upon stimulation with LPA. Blocking CCL2 effectively reduced the pro-migration influence of CM derived from LPA-treated Het-1a. Mechanism studies have demonstrated that LPA activated the NF-κB signaling pathway through LPA1/3, ultimately causing an increase in CCL2 expression and secretion in Het-1a. CONCLUSIONS: Our findings, taken together, demonstrate that CM from LPA-treated esophageal epithelial cells plays a significant role in promoting the progression of ESCC, with CCL2 acting as the primary regulator.

A novel homozygous missense TTC12 variant identified in an infertile Pakistani man with severe oligoasthenoteratozoospermia and primary ciliary dyskinesia.

TTC12 is a cytoplasmic and centromere-localized protein that plays a role in the proper assembly of dynein arm complexes in motile cilia in both respiratory cells and sperm flagella. This finding underscores its significance in cellular motility and function. However, the wide role of TTC12 in human spermatogenesis-associated primary ciliary dyskinesia (PCD) still needs to be elucidated. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify potentially pathogenic variants causing PCD and multiple morphological abnormalities of sperm flagella (MMAF) in an infertile Pakistani man. Diagnostic imaging techniques were used for PCD screening in the patient. Real-time polymerase chain reaction (RT‒PCR) was performed to detect the effect of mutations on the mRNA abundance of the affected genes. Papanicolaou staining and scanning electron microscopy (SEM) were carried out to examine sperm morphology. Transmission electron microscopy (TEM) was performed to examine the ultrastructure of the sperm flagella, and the results were confirmed by immunofluorescence staining. Using WES and Sanger sequencing, a novel homozygous missense variant (c.C1069T; p.Arg357Trp) in TTC12 was identified in a patient from a consanguineous family. A computed tomography scan of the paranasal sinuses confirmed the symptoms of the PCD. RT-PCR showed a decrease in TTC12 mRNA in the patient's sperm sample. Papanicolaou staining, SEM, and TEM analysis revealed a significant change in shape and a disorganized axonemal structure in the sperm flagella of the patient. Immunostaining assays revealed that TTC12 is distributed throughout the flagella and is predominantly concentrated in the midpiece in normal spermatozoa. In contrast, spermatozoa from patient deficient in TTC12 showed minimal staining intensity for TTC12 or DNAH17 (outer dynein arms components). This could lead to MMAF and result in male infertility. This novel TTC12 variant not only illuminates the underlying genetic causes of male infertility but also paves the way for potential treatments targeting these genetic factors. This study represents a significant advancement in understanding the genetic basis of PCD-related infertility.

Photothermal Conversion of the Oleophilic PVDF/Ti3C2Tx Porous Foam Enables Non-Aqueous Liquid System Applicable Actuator.

Various physical and chemical reaction processes occur in non-aqueous liquid systems, particularly in oil phase systems. Therefore, achieving efficient, accurate, controllable, and cost-effective movement and transfer of substances in the oil phase is crucial. Liquid-phase photothermal actuators (LPAs) are commonly used for material transport in liquid-phase systems due to their remote operability and precise control. However, existing LPAs typically rely on materials like hydrogels and flexible polymers, commonly unsuitable for non-aqueous liquids. Herein, a 3D porous poly(vinylidene fluoride) (PVDF)/Ti3C2Tx actuator is developed using a solvent displacement method. It demonstrates directional movement and controlled material transport in non-aqueous liquid systems. When subject to infrared light irradiation (2.0 W cm-2), the actuator achieves motion velocities of 7.3 and 6 mm s-1 vertically and horizontally, respectively. The actuator's controllable motion capability is primarily attributed to the foam's oil-wettable properties, 3D porous oil transport network, and the excellent photothermal conversion performance of Ti3C2Tx, facilitating thermal diffusion and the Marangoni effect. Apart from multidimensional directions, the actuator enables material delivery and obstacle avoidance by transporting and releasing target objects to a predetermined position. Hence, the developed controllable actuator offers a viable solution for effective motion control and material handling in non-aqueous liquid environments.

Evaluation of a novel lysis-based sample processing method to optimize Vibrio vulnificus detecting by loop-mediated isothermal amplification assay.

BACKGROUND: Vibrio vulnificus exists as one of the most serious foodborne pathogens for humans, and rapid and sensitive detection methods are needed to control its infections. As an emerging method, The Loop-Mediated Isothermal Amplification (LAMP) assay has been applied to the early detection of various foodborne pathogens due to its high efficiency, but sample preprocessing still prolongs the complete detection. To optimize the detection process, our study established a novel sample preprocessing method that was more efficient compared to common methods. RESULT: Using V. vulnificus as the detecting pathogen, the water-lysis-based detecting LAMP method shortened the preprocessing time to ≤ 1 min with 100% LAMP specificity; the detection limits of the LAMP assay were decreased to 1.20 × 102 CFU/mL and 1.47 × 103 CFU/g in pure culture and in oyster, respectively. Furthermore, the 100% LAMP specificity and high sensitivity of the water-lysis method were also obtained on detecting V. parahaemolyticus, V. alginolyticus, and P. mirabilis, revealing its excellent LAMP adaption with improvement in sensitivity and efficiency. CONCLUSION: Our study provided a novel LAMP preprocessing method that was more efficient compared to common methods and possessed the practical potential for LAMP application in the future.

Disrupted BRCA1-PALB2 interaction induces tumor immunosuppression and T-lymphocyte infiltration in HCC through cGAS-STING pathway.

BACKGROUND AND AIMS: BRCA1 (BRCA1 DNA repair associated) and PALB2 (partner and localizer of BRCA2) interact with each other to promote homologous recombination and DNA double-strand breaks repair. The disruption of this interaction has been reported to play a role in tumorigenesis. However, its precise function in HCC remains poorly understood. APPROACH AND RESULTS: We demonstrated that mice with disrupted BRCA1-PALB2 interaction were more susceptible to HCC than wild-type mice. HCC tumors arising from these mice showed plenty of T-lymphocyte infiltration and a better response to programmed cell death 1 (PD-1) antibody treatment. Mechanistically, disruption of the BRCA1-PALB2 interaction causes persistent high level of DNA damage in HCC cells, leading to activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in both malignant hepatocytes and M1 macrophages in the tumor microenvironment. The activated cGAS-STING pathway induces programmed cell death 1 ligand 1 expression via the STING-interferon regulatory factor 3 (IRF3)-signal transducer and activator of transcription 1 pathway, causing immunosuppression to facilitate tumorigenesis and tumor progression. Meanwhile, M1 macrophages with an activated cGAS-STING pathway could recruit T lymphocytes through the STING-IRF3 pathway, leading to T-lymphocyte infiltration in tumors. After normalizing immune responses by PD-1 antibody treatment, the infiltrating T lymphocytes attack tumor cells rapidly and effectively. CONCLUSIONS: This study reveals that persistent DNA damage caused by a defective BRCA pathway induces tumor immunosuppression and T-lymphocyte infiltration in HCC through the cGAS-STING pathway, providing insight into tumor immune microenvironment remodeling that may help improve HCC response to PD-1 antibody treatment.

Discrepancy of coordinate system selection in backscattering Mueller matrix polarimetry: exploring photon coordinate system transformation invariants.

In biomedical studies, Mueller matrix polarimetry is gaining increasing attention because it can comprehensively characterize polarization-related vectorial properties of the sample, which are crucial for microstructural identification and evaluation. For backscattering Mueller matrix polarimetry, there are two photon coordinate selection conventions, which can affect the following Mueller matrix parameters calculation and information acquisition quantitatively. In this study, we systematically analyze the influence of photon coordinate system selection on the backscattering Mueller matrix polarimetry. We compare the Mueller matrix elements in the right-handed-nonunitary and non-right-handed-unitary coordinate systems, and specifically deduce the changes of Mueller matrix polar decomposition, Mueller matrix Cloude decomposition and Mueller matrix transformation parameters widely used in backscattering Mueller matrix imaging as the photon coordinate system varied. Based on the theoretical analysis and phantom experiments, we provide a group of photon coordinate system transformation invariants for backscattering Mueller matrix polarimetry. The findings presented in this study give a crucial criterion of parameters selection for backscattering Mueller matrix imaging under different photon coordinate systems.

Molecular and epidemiological characterization of Staphylococcus aureus causing bovine mastitis in China.

BACKGROUND: Staphylococcus aureus is one of the most prevalent pathogens in bovine mastitis, which leads to substantial financial losses for the dairy industry. RESULTS: In this study, S. aureus (n = 72) was isolated from 18 dairy farms in 15 provinces across China in 2021. The identification of these isolates at the species level was achieved by employing 16S rRNA sequencing. An isothermal amplification method for auxiliary detection of S. aureus was established, which can be employed not only for laboratory detection but also for point-of-care testing (POCT). Molecular characteristics of S. aureus mastitis in Chinese dairy cows were determined through MLST and spa typing. Finally, methicillin-resistant Staphylococcus aureus (MRSA) and MRSA resistance genes were detected using MIC and PCR amplification techniques. 72 isolates were identified as 12 sequence types (STs) and 7 clonal complexes (CC). ST1/CC1 was the dominant prevalent accounting for 33.3 % of the total, and exhibiting a wide distribution range. In terms of spa types, t114 was the dominant type, accounting for 31.9 % of the total, followed by t529 as the second major type. Four S. aureus strains were classified as MRSA according to their levels of oxacillin resistance (MIC ≥4 µg/mL). Among these four MRSA strains, one of them was found to be mecA positive. However, the presence of drug-resistance genes mecA and mecC was not detected in the remaining three MRSA strains, indicating the possible existence of new resistance genes. CONCLUSIONS: Our study investigated the prevalence of S. aureus mastitis in dairy cows in China, while also examined the molecular characteristics and MRSA strains. This information will help with the clinical monitoring, prevention, and control of S. aureus mastitis in dairy cattle.

Polarization feature fusion and calculation of birefringence dynamics in complex anisotropic media.

As a complex anisotropic medium, variation in birefringence within biological tissues is closely associated with numerous physiological behaviors and phenomena. In this Letter, we propose a polarization feature fusion method and corresponding polarimetric parameters, which exhibit excellent performance of capturing the birefringence dynamic variation process in complex anisotropic media. By employing the feature fusion method, we combine and transform polarization basis parameters (PBPs) to derive fused polarization feature parameters (FPPs) with explicit expressions. Subsequently, we conduct Monte Carlo (MC) simulation to demonstrate the effectiveness of the proposed FPPs from two variation dimensions of birefringence direction θ and modulus Δn. Leveraging mathematical modeling and linear transformations, we investigate and abstract their response patterns concerning θ and Δn. Finally, the experiments confirm that the FPPs show superior adaptability and interpretability in characterizing the birefringence dynamic process of turbid media. The findings presented in this study provide new, to the best of our knowledge, methodological insights of information extraction for computational polarimetry in biomedical research.

Polarization enhancement mechanism from tissue staining in multispectral Mueller matrix microscopy.

Mueller matrix microscopy can provide comprehensive polarization-related optical and structural information of biomedical samples label-freely. Thus, it is regarded as an emerging powerful tool for pathological diagnosis. However, the staining dyes have different optical properties and staining mechanisms, which can put influence on Mueller matrix microscopic measurement. In this Letter, we quantitatively analyze the polarization enhancement mechanism from hematoxylin and eosin (H&E) staining in multispectral Mueller matrix microscopy. We examine the influence of hematoxylin and eosin dyes on Mueller matrix-derived polarization characteristics of fibrous tissue structures. Combined with Monte Carlo simulations, we explain how the dyes enhance diattenuation and linear retardance as the illumination wavelength changed. In addition, it is demonstrated that by choosing an appropriate incident wavelength, more visual Mueller matrix polarimetric information can be observed of the H&E stained tissue sample. The findings can lay the foundation for the future Mueller matrix-assisted digital pathology.