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The purpose of this study is to analyze FAERS data to identify cases of drug-induced photosensitivity (DIP), examine demographic patterns, determine the drug classes involved, and highlight emerging trends in these reactions. Additionally, we explore potential signal drugs by mining the relevant reported data, aiming to provide insights for safer clinical use of medications. We reviewed the publicly available FAERS database from 2004 to 2023. Using DIP-related search terms such as “photosensitivity reaction,” “polymorphic light eruption,” or et al., we identified reports of DIP. The frequency and trends of these reports were then analyzed. Between 2004 and 2023, the FDA received 17,384,824 reports of adverse reactions, with 20,236 of these linked to DIP. After excluding cases with incomplete data on age, gender, or country of origin, the median patient age was 52 years (IQR = 66). Females comprised 55.71% of the cases (11,274), and 66.96% (12,459) of the reports originated from the United States. The top 45 drugs were responsible for 9,810 cases (48.48%). The three drug classes most commonly associated with DIP in the FAERS database were immunosuppressants, monoclonal antibodies, and antineoplastic agents. A disproportionality analysis of the top drugs revealed several newly identified drugs with signals for photosensitivity, including adalimumab, adapalene, secukinumab, and fingolimod. By analyzing publicly available FAERS data, we identified key themes and trends in DIP reactions. Immunosuppressants and monoclonal antibodies show mild trends in DIP occurrence. Additionally, adalimumab, adapalene, secukinumab, and fingolimod are novel drug signals of DIP.

Landslide disasters occur frequently in the mountainous areas in southwest China, which pose serious threats to the local residents. Interferometry Synthetic Aperture Radar (InSAR) provides us the ability to identify active slopes as potential landslides in vast mountainous areas, to help prevent and mitigate the disasters. Quickly and accurately identifying potential landslides based on massive SAR data is of great significance. Taking the national highway near Wenchuan County, China, as study area, this paper used a Stacking-InSAR method to quickly and qualitatively identify potential landslides based on a total of 40 Sentinel SAR images acquired from November 2017 to March 2019. As a result, 72 active slopes were successfully detected as potential landslides. By comparing the results from Stacking-InSAR with the results from the traditional SBAS-InSAR (Small Baselines Subset) time series method, it was found that the two methods had a high consistency, with 81.7% potential landslides identified by both of the two methods. A detailed comparison on the detection differences was performed, revealing that Stacking-InSAR, compared to SBAS-InSAR may miss a few active slopes with small spatial scales, small displacement levels and the ones affected by the atmosphere, while it has good performance on poor-coherence regions, with the advantages of low technical requirements and low computation labor. The Stacking-InSAR method would be a fast and powerful method to qualitatively and effectively identify potential landslides in vast mountainous areas, with a comprehensive understanding of its specialty and limitations.

Background Due to its high expression capability, recombination of Escherichia coli and pET vector has become the bioengineering preferred expression system. Because β-lactamases mediate bacterial antimicrobial resistance, these enzymes have a substantial clinical impact. Using the E. coli expression system, several kinds of β-lactamases have been produced. However, previous studies have been focused on characterizing target β-lactamases, and the effects of cultivation and induction conditions on the expression efficiency of target enzymes were not addressed. Results Using pET-28a as the cloning vector and E. coli BL21(DE3) as the expression host, this study originally elucidated the effects of IPTG concentration, culture temperature, induction time, and restriction sites on recombinant β-lactamase expression. Moreover, the effects of the target protein length and the 6 × His-tag fusion position on enzyme purification were also explored, and consequently, this study yielded several important findings. (i) Only the signal peptide–detached recombinant β-lactamase could exist in a soluble form. (ii) Low-temperature induction was beneficial for soluble β-lactamase expression. (iii) The closer to the rbs the selected restriction site was, the more difficult it was to express soluble β-lactamase. (iv) The short-chain recombinant protein and the protein with His-tag fused at its C-terminus showed high affinity to the Ni 2+ column. Conclusions Based on our findings, researchers can easily design an effective program for the high production of soluble recombinant β-lactamases to facilitate other related studies.

Tumor immune escape has become a research hotspot in the field of cancer immunotherapy. Tumor-associated macrophages (TAMs) are the key component of tumor microenvironment, which play a pivotal role in tumor immune escape by regulating the immunity checkpoints, inhibiting the activity of T lymphocytes and natural killer (NK) cells, and modulating proportion of different T cells. Stanniocalcin-1(STC1)is ubiquitously expressed in human body, which is proven to involve with tumor progression and clinical prognosis. Recently, STC1 is implicated in tumor microenvironment as a phagocytosis checkpoint, as well as regulates the immunity via macrophages. In the review, we discussed the role of STC1 and TAMs in tumor immunity and their crosstalk, hoping to provide references for the research of STC1 in tumor immunotherapy.

Ginseng residue is a by-product stemming from the commercial extraction of ginsenosides. To assess the disparities between ginseng residue and ginseng tablet, we employed the ultra-high-performance liquid chromatography–quadrupole time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) technique for sample analysis. The analyses revealed the presence of 39 compounds in both ginseng residue and ginseng tablets. Subsequently, the contents of total ginsenosides and total ginseng polysaccharides in the ginseng residue and ginseng tablet were determined. The results indicate that while only a small fraction of ginsenosides remained in the ginseng residue, a significant amount of polysaccharides was retained. Furthermore, our evaluation encompassed the antioxidant activities of both ginseng residue and ginseng tablets. Notably, ginseng residue exhibited robust antioxidant effects, thereby showcasing its potential for recycling as a functional food raw material.

Scorpion is a commonly used drug in traditional Chinese medicine for treating epilepsy, although the exact mechanisms are not yet fully understood. This study aimed to compare the treatment effects of Scorpion water extract (SWE) and Scorpion ethanol extract (SEE) on mice with pentetrazole-induced epilepsy and investigate the possible mechanisms through metabolomics methods. A pentetrazole-induced epileptic mice model was used to assess the corrective effects of SWE and SEE. Untargeted metabolomics, utilizing UPLC-Q-TOF/MS, was employed to analyze the metabolic profiles of mice and identify metabolic changes following scorpion treatment. The results revealed that only SWE showed therapeutic effects in epileptic mice. Metabolomics analysis demonstrated significant alterations in metabolic signatures between the pentetrazole-induced epileptic mice and SWE groups. By utilizing orthogonal partial least squares discrimination analysis, 44 and 108 potential biomarkers in mouse serum were identified in positive and negative ion modes, respectively. Differential metabolites related to epilepsy were then used to pinpoint relevant pathways in epileptic mice, such as linoleic acid metabolism, biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, and ether lipid metabolism. In conclusion, this study highlights the corrective effects of Scorpion on epileptic mice and provides insight into the underlying metabolic pathways involved in its efficacy.

The transcription factor Pitx2 is upregulated in injured neonatal and Hippo-deficient mouse hearts, where it interacts with the Hippo effector protein Yap to activate reactive oxygen species scavengers, thus preventing the heart from oxidative damage. Pitx2 promotes heart regeneration The mammalian heart has only a transient neonatal renewal capacity, so there is therapeutic potential in the possibility of reactivating this capacity in the mature heart. Here James Martin and colleagues identify a mechanism that promotes heart repair both in neonatal mice and in the Hippo-deficient heart regeneration mouse model through upregulation of the Pitx2 transcription factor. Pitx2 interacts with the Hippo pathway effector Yap to activate reactive oxygen species scavengers, thus preventing oxidative damage of the heart. Myocardial infarction results in compromised myocardial function and heart failure owing to insufficient cardiomyocyte self-renewal 1 . Unlike many vertebrates, mammalian hearts have only a transient neonatal renewal capacity 2 . Reactivating primitive reparative ability in the mature mammalian heart requires knowledge of the mechanisms that promote early heart repair. By testing an established Hippo-deficient heart regeneration mouse model for factors that promote renewal, here we show that the expression of Pitx2 is induced in injured, Hippo-deficient ventricles. Pitx2 -deficient neonatal mouse hearts failed to repair after apex resection, whereas adult mouse cardiomyocytes with Pitx2 gain-of-function efficiently regenerated after myocardial infarction. Genomic analyses indicated that Pitx2 activated genes encoding electron transport chain components and reactive oxygen species scavengers. A subset of Pitx2 target genes was cooperatively regulated with the Hippo pathway effector Yap. Furthermore, Nrf2, a regulator of the antioxidant response 3 , directly regulated the expression and subcellular localization of Pitx2 . Pitx2 mutant myocardium had increased levels of reactive oxygen species, while antioxidant supplementation suppressed the Pitx2 loss-of-function phenotype. These findings reveal a genetic pathway activated by tissue damage that is essential for cardiac repair.

Background Head and neck squamous cell carcinoma (HNSCC) is an aggressive and heterogeneous malignancy, presenting challenges in accurately forecasting prognosis and immunotherapy response. This study endeavors to develop a robust gene signature to augment the prognostic prediction of HNSCC, and simultaneously uncover potential immunotherapy combination drug. Methods Transcriptome data from clinical HNSCC patients were analyzed using LASSO regression algorithm to construct a gene signature, followed by survival curve and ROC curve analyses, immune correlation analysis, and nomogram building. Furthermore, a comprehensive virtual screening of approximately 30,000 molecules was carried out based on the key target of signature. Finally, the potential immunotherapy combination drug was identified by molecular docking, CCK-8 assay, RT-qPCR assay, and molecular dynamics simulation. Results An anti-tumor immune gene signature (ATIGS) comprising 14 genes was established, which had promising potential in predicting the prognosis of HNSCC patients and could serve as an independent prognostic factor. Notably, ATIGS demonstrated a significant correlation with the infiltration level of several immune cells in the tumor immune microenvironment. It also had a good performance in predicting the response to immunotherapy. Further, protein–protein interaction (PPI) network analysis identified ZAP70 as a key target of ATIGS. Virtual screening of ~ 30,000 compounds found Puerol A, 4′-Hydroxywogonin, and Cirsimaritin as candidates, with 4′-Hydroxywogonin showing the strongest inhibition of CAL-27 and SCC7 cells. It also upregulated the expression levels of immune-related genes ZAP70 and LAT in CAL-27 cells, hinting at anti-tumor effect via immune pathway regulation. Molecular dynamics simulation showed stable binding of 4′-Hydroxywogonin to ZAP70 through hydrogen bonds and hydrophobic interactions, involving residues ALA417, GLU295, and LYS369. Conclusions This study successfully constructed a robust gene signature ATIGS, as well as identified a potential immunotherapy combination drug 4′-Hydroxywogonin. The ATIGS could effectively predict the prognosis and immunotherapy response of HNSCC patients, which may contribute towards enriching the immunotherapy-responsive population and enhancing the clinical efficacy of immunotherapy. Meanwhile, 4′-Hydroxywogonin may provide a promising clinical treatment strategy.

Highly sensitive and selective monitoring of amino metabolites such as glutamine, arginine, tryptophan and related proteins played significant roles in early diagnosis and warning of lymphoma. But those limited abundance and lacked chromophore group in vivo were bottleneck of multivariate analysis. This work aims to develop a novel UHPLC-Triple-TOF-HRMS method for simultaneous quantitation of 20 kinds of amino metabolites and tracing different proteins based on a new mass spectrometry probe (3-bromopropyl) triphenylphosphonium (3-BMP) with ability of enhance ionization efficiency and targeted labeling amino functional groups. An excellent linearity with R 2  ≥ 0.9995 and inter- and intra-day RSD were 1.43-5.22% and 1.22-5.87%, respectively. Satisfactory recoveries were 87.09-95.82%. Limit of detection (S/ N  = 3) was 4.0–12.0 fmol. Further, up-regulated haptoglobin, coagulation factor VII and catalase could directly negatively regulate Ala, Lys and Phe, which caused Trp, His, Ser, Asp and Pro expression decreased significantly in lymphoma patients ( p  < 0.05). Ultimately, a machine learning model was established to predict lymphoma with accuracy rate of 93.68%. Above all, this study would provide multivariate analysis strategy for in-depth explore relationship aminos associated proteins and pathogenesis and helpful for early warning of lymphoma patients under free-disease state.

Increasing crop production is necessary to feed the world’s expanding population, and crop breeders often utilize genetic variations to improve crop yield and quality. However, the narrow diversity of the wheat D genome seriously restricts its selective breeding. A practical solution is to exploit the genomic variations of Aegilops tauschii via introgression. Here, we established a rapid introgression platform for transferring the overall genetic variations of A. tauschii to elite wheats, thereby enriching the wheat germplasm pool. To accelerate the process, we assembled four new reference genomes, resequenced 278 accessions of A. tauschii and constructed the variation landscape of this wheat progenitor species. Genome comparisons highlighted diverse functional genes or novel haplotypes with potential applications in wheat improvement. We constructed the core germplasm of A. tauschii , including 85 accessions covering more than 99% of the species’ overall genetic variations. This was crossed with elite wheat cultivars to generate an A. tauschii -wheat synthetic octoploid wheat (A-WSOW) pool. Laboratory and field analysis with two examples of the introgression lines confirmed its great potential for wheat breeding. Our high-quality reference genomes, genomic variation landscape of A. tauschii and the A-WSOW pool provide valuable resources to facilitate gene discovery and breeding in wheat. An introgression platform for transferring genetic variations of Aegilops tauschii to hexaploid wheat is established based on synthetic octoploid wheat. Combined with newly generated genome resources of A. tauschii , it represents a powerful tool for wheat gene discovery and breeding.