Case report and literature review: management of Paxlovid (nirmatrelvir/ritonavir)-induced acute tacrolimus toxicity in a patient with systemic lupus erythematosus.

Despite the availability of effective vaccines and treatments for SARS-CoV-2, managing COVID-19 in patients with systemic lupus erythematosus (SLE) remains challenging, particularly considering drug-drug interactions (DDIs). Here, we present a case of DDIs between Tacrolimus (Tac) and nirmatrelvir/ritonavir (NMV/r) in a 32-year-old male with SLE. Following self-administration of NMV/r and resumption of Tac after 5 days, the patient experienced acute nephrotoxicity and neurotoxicity, accompanied by supratherapeutic Tac levels, despite Tac being withheld during NMV/r. The primary cause of this acute toxicity is attributed to ritonavir's inhibitory effect on both CYP3A4 enzymes and P-glycoprotein. Upon admission, Tac was discontinued, and supportive therapies were initiated. Phenytoin, a CYP3A4 inducer, was administered to lower Tac levels under the guidance of clinical pharmacists, effectively alleviating the patient's acute toxic symptoms. The half-life of Tac during the treatment of phenytoin was calculated to be 55.87 h. And no adverse reactions to phenytoin were observed. This case underscores the persistence of enzyme inhibition effects and demonstrates the effectiveness and safety of utilizing CYP3A4 enzyme inducers to mitigate Tac concentrations. Furthermore, it emphasizes the importance of healthcare providers and patients being vigilant about DDIs in Tac recipients. Lastly, it highlights the indispensable role of pharmacist involvement in clinical decision-making and close monitoring in complex clinical scenarios. Although our findings are based on a single case, they align with current knowledge and suggest the potential of individualized combination therapy in managing challenging COVID-19 cases in immunocompromised patients.

Nemo mRNA vaccination improves airway barrier function in mice with airway allergy.

Epithelial barrier dysfunction plays an important role in the pathogenesis of Th2 bias. The mechanism requires further clarification. NEMO is associated with regulating apoptotic activities in the cell. The purpose of this study is to investigate the role of insufficient Nemo signals in developing Th2 bias in the respiratory tract. Nemof/fEpcam-Cre mice (A mouse strain carrying NEMO-deficient epithelial cells. NemoKO mice, in short) was generated. An airway Th2 bias mouse model was established with the ovalbumin/alum protocol. The NemoKO mice exhibited spontaneous airway Th2 bias. Respiratory tract epithelial barrier integrity was compromised in NemoKO mice. Apoptosis was found in approximately 10% of the epithelial cells of the respiratory tract in NemoKO mice. The reconstruction of the Nemo expression restored homeostasis within the epithelial barrier of the airways. Restoration of Nemo gene expression in epithelial cells by Nemo mRNA vaccination alleviated Th2 bias in mice with airway allergy. To sum up, NEMO plays an important role in maintaining the integrity of the epithelial barrier in the respiratory tract. Administration of NEMO mRNA vaccines can restore epithelial barrier functions and alleviate Th2 bias in the airways.

Genome-Wide Analysis of the SAUR Gene Family and Its Expression Profiles in Response to Salt Stress in Santalum album.

The SAUR (small auxin-up RNA) family constitutes a category of genes that promptly respond to the hormone auxin and play a pivotal role in diverse biological processes encompassing plant growth and the response to abiotic stress. Santalum album L., a semi-parasitic evergreen tree, is renowned for its economically valuable essential oils, positioning it among the most prized tree species. In this study, a meticulous identification and comprehensive analysis of 43 SAUR genes was conducted within S. album. Based on phylogenetic relationships, the SaSAUR genes were systematically categorized into five groups. A collinearity analysis revealed intriguing insights, disclosing 14 segmental duplications and 9 tandem duplications within the SaSAUR genes, emphasizing the pivotal role of duplication in the expansion of this gene family. Noteworthy variations in the expression levels of SaSAUR genes were observed by delving into the SaSAUR transcriptome data from various tissues, including leaves, roots, and heartwood, as well as under salt-stress conditions. Notably, SaSAUR08 and SaSAUR13 were significantly upregulated in heartwood compared with roots and leaves, while SaSAUR18 was markedly more expressed in roots compared with heartwood and leaves. Furthermore, SaSAUR27 and SaSAUR28 were found to respond closely to salt stress, hinting at their potential involvement in the salt-stress response mechanism. This research offers a comprehensive investigation of SAUR genes in S. album and establishes a foundation for future exploration of the SAUR gene family, particularly its relation to growth and salt-stress responses.

Multi-scale perceptual YOLO for automatic detection of clue cells and trichomonas in fluorescence microscopic images.

Vaginitis is a common disease among women and has a high recurrence rate. The primary diagnosis method is fluorescence microscopic inspection, but manual inspection is inefficient and can lead to false detection or missed detection. Automatic cell identification and localization in microscopic images are necessary. For vaginitis diagnosis, clue cells and trichomonas are two important indicators and are difficult to be detected because of the different scales and image characteristics. This study proposes a Multi-Scale Perceptual YOLO (MSP-YOLO) with super-resolution reconstruction branch to meet the detection requirements of clue cells and trichomonas. Based on the scales and image characteristics of clue cells and trichomonas, we employed a super-resolution reconstruction branch to the detection network. This branch guides the detection branch to focus on subtle feature differences. Simultaneously, we proposed an attention-based feature fusion module that is injected with dilated convolutional group. This module makes the network pay attention to the non-centered features of the large target clue cells, which contributes to the enhancement of detection sensitivity. Experimental results show that the proposed detection network MSP-YOLO can improve sensitivity without compromising specificity. For clue cell and trichomoniasis detection, the proposed network achieved sensitivities of 0.706 and 0.910, respectively, which were 0.218 and 0.051 higher than those of the baseline model. In this study, the characteristics of the super-resolution reconstruction task are used to guide the network to effectively extract and process image features. The novel proposed network has an increased sensitivity, which makes it possible to detect vaginitis automatically.

Comparative Analysis of Codon Usage Patterns in Nuclear and Chloroplast Genome of Dalbergia (Fabaceae).

The Dalbergia plants are widely distributed across more than 130 tropical and subtropical countries and have significant economic and medicinal value. Codon usage bias (CUB) is a critical feature for studying gene function and evolution, which can provide a better understanding of biological gene regulation. In this study, we comprehensively analyzed the CUB patterns of the nuclear genome, chloroplast genome, and gene expression, as well as systematic evolution of Dalbergia species. Our results showed that the synonymous and optimal codons in the coding regions of both nuclear and chloroplast genome of Dalbergia preferred ending with A/U at the third codon base. Natural selection was the primary factor affecting the CUB features. Furthermore, in highly expressed genes of Dalbergia odorifera, we found that genes with stronger CUB exhibited higher expression levels, and these highly expressed genes tended to favor the use of G/C-ending codons. In addition, the branching patterns of the protein-coding sequences and the chloroplast genome sequences were very similar in the systematic tree, and different with the cluster from the CUB of the chloroplast genome. This study highlights the CUB patterns and features of Dalbergia species in different genomes, explores the correlation between CUB preferences and gene expression, and further investigates the systematic evolution of Dalbergia, providing new insights into codon biology and the evolution of Dalbergia plants.

The Role of Leukotriene B4 in Cow Metritis.

Introduction: Metritis is a common postpartum disease in dairy cows. As a mast cell (MC) mediator, leukotriene B4 (LTB4) is the strongest phagocyte chemokine. It is important in inflammation for the recruitment of immune cells to resist infection. This study investigated the effect of LTB4 in metritis. Material and Methods: Twenty Holstein cows 3 to 6 years old and at 6 to 10 days postpartum were selected, ten of which with postpartum metritis were the experimental group, and the other ten of which as healthy cows were the control group. The levels of LTB4, substance P (SP) and vasoactive intestinal peptide (VIP) were measured by ELISA, the expression of LTB4 receptor 2 (BLT2), matrix metalloproteinase (MMP)-2 and MMP-9 mRNA was measured by qPCR, and collagens I and IV were detected by immunohistochemical staining. Results: Concentrations of SP and LTB4 were significantly higher, but those of VIP were significantly lower in the experimental group than those in the control group. The expression of BLT2, MMP-2 and MMP-9 mRNA was significantly higher in the experimental group than that in the control group. The expression of collagen Ⅰ and collagen Ⅳ was significantly lower in the experimental group than that in the control group. Conclusion: In metritis, SP promotes the activation of MC and the synthesis and release of LTB4. Leukotriene B4 chemotactic immune cells promote the high expression of collagenase, which accelerated the hydrolysis of collagen, while the inhibitory effect of VIP on MC was weakened. This may further aggravate the damage to uterine tissue.

Genome-wide characterization of R2R3-MYB gene family in Santalum album and their expression analysis under cold stress.

Sandalwood (Santalum album) is a high-value multifunctional tree species that is rich in aromatic substances and is used in medicine and global cosmetics. Due to the scarcity of land resources in tropical and subtropical regions, land in temperate regions is a potential resource for the development of S. album plantations in order to meet the needs of S. album production and medicine. The R2R3-MYB transcription factor family is one of the largest in plants and plays an important role in the response to various abiotic stresses. However, the R2R3-MYB gene family of S. album has not been studied. In this study, 144 R2R3-MYB genes were successfully identified in the assembly genome sequence, and their characteristics and expression patterns were investigated under various durations of low temperature stress. According to the findings, 31 of the 114 R2R3-MYB genes showed significant differences in expression after cold treatment. Combining transcriptome and weighted gene co-expression network analysis (WGCNA) revealed three key candidate genes (SaMYB098, SaMYB015, and SaMYB068) to be significantly involved in the regulation of cold resistance in S. album. The structural characteristics, evolution, and expression pattern of the R2R3-MYB gene in S. album were systematically examined at the whole genome level for the first time in this study. It will provide important information for future research into the function of the R2R3-MYB genes and the mechanism of cold stress response in S. album.

Academic achievement is more closely associated with student-peer relationships than with student-parent relationships or student-teacher relationships.

Introduction: Personal relationships have long been a concern in education. Most studies indicate that good personal relationships are generally positively correlated with academic performance. However, few studies have compared how different types of personal relationships correlate with academic performance, and the conclusions of existing studies are inconsistent. Based on a large sample, the current study compared how the three closest types of personal relationships among students (with parents, teachers, and their peers) compared with their academic performance. Methods: Cluster sampling was used to issue questionnaires to students in Qingdao City, Shandong Province, China in 2018 (Study 1) and in 2019 (Study 2). The actual sample size included 28168 students in Study 1 and 29869 students in Study 2 (both studies, Grades 4 and 8), thus totaling 58037 students. All students completed a personal relationship questionnaire and several academic tests. Results: The results showed that: (1) the quality of personal relationships significantly and positively correlated with academic performance; (2) Among the three types of relationships tested, the quality of student-peer relationships was the most closely associated with academic achievement. Discussion: This study gives insights into future research directions in this field and also reminds educators to pay attention to the personal relationships among their students, especially peer relationships.

Multicolor ultralong phosphorescence from perovskite-like octahedral α-AlF3.

Designing organic fluorescent and phosphorescent materials based on various core fluorophore has gained great attention, but it is unclear whether similar luminescent units exist for inorganic materials. Inspired by the BX6 octahedral structure of luminescent metal halide perovskites (MHP), here we propose that the BX6 octahedron may be a core structure for luminescent inorganic materials. In this regard, excitation-dependent color-tunable phosphorescence is discovered from α-AlF3 featuring AlF6 octahedron. Through further exploration of the BX6 unit by altering the dimension and changing the center metal (B) and ligand (X), luminescence from KAlF4, (NH4)3AlF6, AlCl3, Al(OH)3, Ga2O3, InCl3, and CdCl2 are also discovered. The phosphorescence of α-AlF3 can be ascribed to clusterization-triggered emission, i.e., weak through space interaction of the n electrons of F atoms bring close proximity in the AlF6 octahedra (inter/intra). These discoveries will deepen the understanding and contribute to further development of BX6 octahedron-based luminescent materials.

Detection of Imatinib Based on Electrochemical Sensor Constructed Using Biosynthesized Graphene-Silver Nanocomposite.

The establishment of a monitoring technique for imatinib is necessary in clinical and environmental toxicology. Leaf extracts of Lycoris longituba were used as reducing agent for the one-step synthesis of reduced graphene oxide-Ag nanocomposites. This nanocomposite was characterized by TEM, FTIR, XRD, and other instruments. Then, the graphene/Ag nanocomposite was used as a modifier to be cemented on the surface of the glassy carbon electrode. This electrode exhibited excellent electrochemical sensing performance. Under the optimal conditions, the proposed electrode could detect imatinib at 10 nM-0.28 mM with a low limit of detection. This electrochemical sensor also has excellent anti-interference performance and reproducibility.

Color-tunable ultralong room temperature phosphorescence from EDTA.

Unexpected color-tunable ultralong room-temperature phosphorescence (RTP, τ∼0.5 s) was observed from EDTA (and also EDTA salts, chelates, and structural analogues). Through both experimental and theoretical investigations, the through-space conjugation of the lone pair n electrons of N/O atoms in EDTA was identified as the origin of RTP. The results here will be important for further developing phosphors with ultralong emission lifetime.

Ultralong Room-Temperature Phosphorescence from Boric Acid.

For a long time, phosphors with long-lived emission are dominated by rare earth/transition metal ion-doped sulfides and oxides. Recently, organic materials capable of emitting long-lived room-temperature phosphorescence (RTP) are reported, carbon skeletons are almost the exclusive structural feature of the conjugated luminophores. Herein, we reported that boric acid, a non-metal and C-free material, could emit RTP with lifetime up to 0.3 s. Detailed investigations indicated the weak conjugation between the n electrons of the O atoms in the B-O confined space was the possible origin of RTP. Similar RTP was also found in electron-rich N/F systems, namely, BN and BF3 (BF4 - ). Importantly, the vacant p z 0 orbital of B was found to contribute to the relevant unoccupied molecular orbitals involved in excitation, which is different from previous reports on phosphorescence from arylboronic acids. The results confirm the unique role of B as a versatile structure motif for construction of new RTP materials.

Genome-wide identification and functional analysis of ARF transcription factors in Brassica juncea var. tumida.

Auxin signalling is vital for plant growth and development, from embryogenesis to senescence. Recent studies have shown that auxin regulates biological processes by mediating gene expression through a family of functionally original DNA-binding auxin response factors, which exist in a large multi-gene family in plants. However, to date, no information has been available about characteristics of the ARF gene family in Brassica juncea var. tumida. In this study, 65 B. juncea genes that encode ARF proteins were identified in the B. juncea whole-genome, classified into three phylogenetical groups and found to be widely and randomly distributed in the A-and B-genome. Highly conserved proteins were also found within each ortholog based on gene structure and conserved motifs, as well as clustering level. Furthermore, promoter cis-element analysis of BjARFs demonstrated that these genes affect the levels of plant hormones, such as auxin, salicylic, gibberellin acid, MeJA, abscisic acid, and ethylene. Expression analysis showed that differentially expressed BjARF genes were detected during the seedling stage, tumor stem development and the flowering period of B. juncea. Interestingly, we found that BjARF2b_A, BjARF3b_A, BjARF6b_A, and BjARF17a_B were significantly expressed in tumor stem, and an exogenous auxin assay indicated that these genes were sensitive to auxin and IAA signaling. Moreover, eight of the nine BjARF10/16/17 genes and all of the BjARF6/8 genes were involved in post-transcriptional regulation, targeted by Bj-miR160 and Bj-miR167c, respectively. This analysis provides deeper insight of diversification for ARFs and will facilitate further dissection of ARF gene function in B. juncea.

Establishment and Application of Polymerase Spiral Reaction Amplification for Salmonella Detection in Food.

Salmonella is a common zoonotic and foodborne pathogen that causes high morbidity and mortality in developing countries. In this study, we established and validated a polymerase spiral reaction (PSR) assay which targeted the conserved invasion gene (invA) of Salmonella by SYBR Green I indicator methods. Subsequently, assays for determination of the optimal conditions for optimal specificity and sensitivity of PSR were performed. We performed comprehensive evaluations using loop-mediated isothermal amplification (LAMP) and realtime PCR. A total number of 532 samples of daily food were analyzed by PSR. Twenty-seven bacterial strains were tested in the specificity assay, from which positive results were obtained only for 14-Salmonella strains. However, none of the 13 non-Salmonella strains was amplified. Similarly with LAMP and real-time PCR, the detection limit of the PSR assay was 50 CFU/ml. The PSR method was also successfully applied to evaluate the contamination with Salmonella in 532 samples of daily food, corroborating traditional culture method data. The novel PSR method is simple, sensitive, and rapid and provides new insights into the prevention and detection of foodborne diseases.

Elimination of ethanethiol released from municipal wastes by absorption sequencing electrochemical oxidation.

As a typical municipal waste landfill gas, ethanethiol can become an air pollutant because of its low odor threshold concentration and toxicity to human beings. A hybrid process of absorption combined with electrochemical oxidation to degrade ethanethiol was investigated. The ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM]BF4) was employed as an absorbent to capture ethanethiol from the air stream. Electrochemical oxidation demonstrated that ethanethiol could be oxidized on a ß-PbO2 anode modified with fluoride, while [BMIM]BF4 was used as an electrolyte. After a reaction time of 90 min under a current density of 50 mA/cm2, ethanethiol could be thoroughly destructed by the successive attack of hydroxyl radicals (·OH) electrogenerated on the surface of the ß-PbO2 anode, while the sulfur atoms in ethanethiol were ultimately converted to sulfate ions [Formula: see text]. The reaction mechanism is proposed, and the operating condition is also estimated with a kinetic model. This hybrid process could be a promising way to remove thiol compounds from municipal waste landfill gases.