Multiple Roles of Anions on the Degradation Efficiency and Mineralization Pathway of Recalcitrant Acetaldehyde by Vacuum Ultraviolet (185 nm) Oxidation.

Vacuum-UV (185 nm, VUV) is widely applied to polish reverse osmosis permeate (ROP), such as the production of electronics-grade ultrapure water. In this study, the VUV oxidation of acetaldehyde, a common carbonyl in ROP, was found to be influenced by anions even at low concentrations. Interestingly, the influencing extent and mechanism varied depending on the anions. Bicarbonate minimally affected the VUV-photon absorption and •OH consumption, but at 5000 µg-C·L-1, it decreased the degradation of acetaldehyde by 58.7% possibly by scavenging organic radicals or other radical chain reactions. Nitrate strongly competed for VUV-photon absorption and •OH scavenging through the formation of nitrite, and at 500 µg-N·L-1, it decreased the removal rate of acetaldehyde degradation by 71.2% and the mineralization rate of dissolved organic carbon by 53.4%. Chloride competed for VUV-photon absorption and also generated reactive chlorine species, which did not affect acetaldehyde degradation but influenced the formation of organic byproducts. The radical chain reactions or activation of anions under VUV irradiation could compensate for the decrease in oxidation performance and need further investigation. In real ROPs, the VUV oxidation of acetaldehyde remained efficient, but mineralization was hindered due to nitrate and chloride anions. This study deepens the understanding of the photochemistry and feasibility of VUV in water with low concentrations of anions.

Mineralogy and Geochemistry of Rare Earth Elements in Carboniferous-Permian Coals at the Eastern Margin of the Ordos Basin.

This article used Carboniferous-Permian coals from the Jungar, Hedong, and Weibei Coalfields in the east of the Ordos Basin as research samples. Characteristics of coal quality, petrology, mineralogy, and geochemistry were analyzed by proximate analysis, inductively coupled plasma mass spectrometry, X-ray fluorescence spectroscopy, X-ray diffraction analysis, scanning electron microscopy-energy spectrum analysis, and incident light microscope. The enrichment regulations, distribution patterns, and occurrences of REY (rare earth element and yttrium) in coal under different geological conditions were compared. Geological significance and the influence of REY were then discussed. The average REY of Permian coal in the eastern margin of the basin is 127.9 µg/g, CC = 1.87, and the average REY of Carboniferous coal is 117.49 µg/g, CC = 1.72, which are within the normal enrichment range. The inorganic affinity of REYs in the study area is strong and mainly occurs in clay minerals and detrital phosphates and correlates well with LREY. The Permian coal sedimentary environment is more oxidized than the Taiyuan formation, and the Carboniferous coal sedimentary environment is noticeably more affected by marine water. With an increasing degree of coalification, the concentration of rare earth elements (REE) in high-rank coal vitrinite is lower than that in inertinite. In contrast, the concentration of REEs in low-rank coal is the opposite. This is because the oxygen-containing functional groups that can combine with REEs in vitrinite reduce significantly, resulting in the loss of trace elements into other forms. The provenance of the northern and central regions of the study area is mainly sedimentary rocks, granite, alkaline basalt, and continental tholeiite, while the southern region is mainly granite and sedimentary rocks.

Isotropic Quantum Griffiths Singularity in Nd_{0.8}Sr_{0.2}NiO_{2} Infinite-Layer Superconducting Thin Films.

This work reports on the emergence of quantum Griffiths singularity (QGS) associated with the magnetic field induced superconductor-metal transition (SMT) in unconventional Nd_{0.8}Sr_{0.2}NiO_{2} infinite layer superconducting thin films. The system manifests isotropic SMT features under both in-plane and perpendicular magnetic fields. Importantly, after scaling analysis of the isothermal magnetoresistance curves, the obtained effective dynamic critical exponents demonstrate divergent behavior when approaching the zero-temperature critical point B_{c}^{*}, identifying the QGS characteristics. Moreover, the quantum fluctuation associated with the QGS can quantitatively explain the upturn of the upper critical field around zero temperature for both the in-plane and perpendicular magnetic fields in the phase boundary of SMT. These properties indicate that the QGS in the Nd_{0.8}Sr_{0.2}NiO_{2} superconducting thin film is isotropic. Moreover, a higher magnetic field gives rise to a metallic state with the resistance-temperature relation R(T) exhibiting lnT dependence among the 2-10 K range and T^{2} dependence of resistance below 1.5 K, which is significant evidence of Kondo scattering. The interplay between isotropic QGS and Kondo scattering in the unconventional Nd_{0.8}Sr_{0.2}NiO_{2} superconductor can illustrate the important role of rare region in QGS and help to uncover the exotic superconductivity mechanism in this system.

MEIKIN expression and its C-terminal phosphorylation by PLK1 is closely related the metaphase-anaphase transition by affecting cyclin B1 and Securin stabilization in meiotic oocyte.

Oocyte meiotic maturation failure and chromosome abnormality is one of the main causes of infertility, abortion, and diseases. The mono-orientation of sister chromatids during the first meiosis is important for ensuring accurate chromosome segregation in oocytes. MEIKIN is a germ cell-specific protein that can regulate the mono-orientation of sister chromatids and the protection of the centromeric cohesin complex during meiosis I. Here we found that MEIKIN is a maternal protein that was highly expressed in mouse oocytes before the metaphase I (MI) stage, but became degraded by the MII stage and dramatically reduced after fertilization. Strikingly, MEIKIN underwent phosphorylation modification after germinal vesicle breakdown (GVBD), indicating its possible function in subsequent cellular event regulation. We further showed that MEIKIN phosphorylation was mediated by PLK1 at its carboxyl terminal region and its C-terminus was its key functional domain. To clarify the biological significance of meikin degradation during later stages of oocyte maturation, exogenous expression of MEIKIN was employed, which showed that suppression of MEIKIN degradation resulted in chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest through a spindle assembly checkpoint (SAC)-independent mechanism. Exogenous expression of MEIKIN also inhibited metaphase II (MII) exit and early embryo development. These results indicate that proper MEIKIN expression level and its C-terminal phosphorylation by PLK1 are critical for regulating the metaphase-anaphase transition in meiotic oocyte. The findings of this study are important for understanding the regulation of chromosome segregation and the prevention meiotic abnormality.

Salvage surgery and conversion surgery for patients with non-small cell lung cancer: A narrative review.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths. With the development of screening, patient selection and treatment strategies, patients' survival outcomes and living quality significantly improved. However, some patients still have local recurrence or residual tumors after receiving definitive therapies. Salvage surgery has been regarded as an effective option for recurrent or residual NSCLC, but its effectiveness remains undetermined. Furthermore, conversion surgery is a special type of salvage surgery for tumors converted from "initially unresectable" to "potentially resectable" status due to a favorable response to systemic treatments. Although conversion surgery is a promising curative procedure for advanced NSCLC, its concept and clinical value remain unfamiliar to clinicians. In this narrative review, we provided an overview of the safety and efficacy of salvage surgery, especially salvage surgery after sublobar resection in early-stage NSCLC. More importantly, we highlighted the concept and value of conversion surgery after systemic treatment in advanced NSCLC to gain some insights into its role in the treatment of lung cancer.

Occurrence of Fusarium Crown Rot Caused by Fusarium culmorum on Winter Wheat in Xinjiang Uygur Autonomous Region, China.

Wheat (Triticum aestivum L.) is the predominant grain crop and plays a pivotal role in grain production in Xinjiang Uygur Autonomous Region (XUAR), China. Its cultivated area constitutes approximately half of the total sown area of grain crops in XUAR, with 1.14 million hectares in 2021. Fusarium crown rot (FCR) of wheat, caused by Fusarium culmorum (W.G. Smith) Sacc., is one of the most devastating soil-borne diseases known to seriously reduce grain yield (Ma et al. 2024; Saad et al. 2023). In 2016, FCR of wheat, caused by F. culmorum, was firstly identified in Henan Province, China (Li et al. 2016). In June 2023, during the investigation of FCR of wheat in Aksu Prefecture, XUAR, FCR on winter wheat (cv. Xindong 20) was found (82.761349°E, 41.612202°N). The grain-filling period for winter wheat in early June coincided with a period of high temperatures and water demand in Aksu Prefecture. Approximately 8% of the Xindong 20 wheat plants exhibited symptoms of white heads and browning at the stem base, with the disease present in 82% of the wheat fields surveyed. To identify the pathogens, 20 samples of diseased stem basal tissue, each 0.5 cm in length, were collected and sterilized with 75% alcohol for 30s and 5% NaOCl solution for 2 min, followed by three rinses with sterile water. These samples were then plated onto potato dextrose agar (PDA) medium at 25°C for 5 days. A total of 17 isolates with consistent morphological characteristics were obtained using single-spore technique, with an isolation rate of 85%. The isolated strains exhibited rapid growth on PDA, producing fluffy, pale-yellow hyphae, and accumulating a pale-yellow to dark red pigment on the bottom of the medium. On carnation leaf agar (CLA), these strains formed orange colonies due to the aggregation of a large number of macroconidia. The macroconidia were short and thick, with three to four septa and rounded apical cell, averaging 31.94 to 40.96 × 5.62 to 6.71 µm (Magnification of ×400). Microconidia were not observed. These morphological characters were consistent with those of F. culmorum (Leslie and Summerell. 2006). Two isolates (D-9 and D-11) were selected for molecular identification. The EF-1α gene fragment was amplified using primers EF1/EF2 (5'-ATGGGTAAGGARGACAAGAC-3'/5'-GGARGTACCAGTSATCATG-3') as previously described by O'Donnell et al. (1998). The two 665 bp PCR products were sequenced and submitted to GenBank (GenBank Accession No: PP763247 and PP763248) with 99. 7% identity to the published F. culmorum sequences (e.g., OP985478, OP985477, MG195126, KX702638). The molecular identification was further confirmed by F. culmorum species-specific PCR primers FcOIF/FcOIR (Nicholson et al. 1998). The expected PCR products of 553 bp were produced only in F. culmorum. Strains D-9 and D-11 were used to conduct the pathogenicity experiment on 7-day-old winter wheat (cv. Xindong 20) using drip in the lower stem inoculation method with a 10-µl of 106 macroconidia ml-1 suspension, and the control 7-day-old winter wheat were treated with sterile water (Xu et al. 2017). The experiments were replicated five times in a greenhouse at temperatures ranging from 20℃ to 25℃. After 4 weeks, all inoculated wheat seedlings showed stem base browning or even death. No symptoms were observed on the control plants. The fungus was reisolated from all inoculated wheat plants by the method described above and identified by morphological and PCR amplification using F. culmorum species-specific primers FcOIF/FcOIR. No F. culmorum was isolated from the control wheat plants, fulfilling Koch's postulates. To the best of our knowledge, this is the first report of F.culmorum causing FCR on winter wheat in XUAR, China. Considering wheat is the predominant grain crop and plays a pivotal role in grain production in China, necessary measures should be taken to prevent the spread of F. culmorum to other regions.

Self-Assembled Chiral Polymers Exhibiting Amplified Circularly Polarized Electroluminescence.

Circularly polarized electroluminescence (CPEL) is highly promising in realm of 3D display and optical data storage. However, designing a groundbreaking chiral material with high comprehensive CPEL performance remains a formidable challenge. In this work, a pair of chiral polymers with self-assembled behavior is designed by integrating a chiral BN-moiety into polyfluorene backbone, named R-PBN and S-PBN, respectively. The chiral polymers show narrowband emission centered at 490 nm with full-width half maximum (FWHM) of 29 nm and high photoluminescence quantum yield (PLQY) of 79%. After thermal annealing treatment, the chiral polymers undergo self-assembly, exhibiting amplified circularly polarized luminescence (CPL) with asymmetry factor (|glum|) of up to 0.11. Moreover, the solution-processed nondoped CP-OLEDs based on the chiral polymers as emitting layers exhibit maximum external quantum efficiency (EQEmax) of 9.8%, intense CPEL activities with |gEL| of up to 0.07, and small FWHM of 36 nm, simultaneously. This represents the first case of self-assembled chiral polymers that combines high EQE, large gEL value and narrowband emission.

Disinfection-residual bacteria (DRB) after chlorine dioxide treatment: Microbial community structure, regrowth potential, and secretion characteristics.

This study investigates the effects of chlorine dioxide (ClO2) disinfection on the community structure, regrowth potential, and metabolic product secretion of disinfection-residual bacteria (DRB) in secondary effluent (SE), denitrification filter effluent (DFE), and ultrafiltration effluent (UE). Results show that ClO2 effectively reduces bacteria in SE and UE, achieving log removal values exceeding 3 at 1 mg/L within 30 min. A salient positive correlation (R2 > 0.95) exists between changes in total fluorescence intensity and disinfection efficacy. Post-treatment, Acinetobacter abundance increased in SE, while Pseudomonas decreased in DFE and UE. At lower ClO2 concentrations, Staphylococcus, Mycobacterium, Aeromonas, and Lactobacillus increased in DFE, but decreased at higher concentrations. After storage, bacterial counts in disinfected samples exceeded those in the control group, surpassing 105 CFU/mL. Despite an initial decline, species richness and evenness partially recovered but remained lower than control levels. Culturing DRB for 72 h showed elevated extracellular polymeric substances (EPS) secretion, quantified as total organic carbon (TOC), ranging from 5 to 27 mg/L, with significantly higher EPS in the disinfection group. Parallel factor analysis with self-organizing maps (PARAFAC-SOM) effectively differentiated water sample types and EPS fluorescent substances, underscoring the potential of three-dimensional fluorescence as an indirect measure of ClO2 disinfection efficacy.

[Chemical composition and pharmacological effects of Cinnamomum camphora chvar. borneol essential oil: a review].

Cinnamomum camphora chvar. borneol, a rare camphor tree variant recently identified in China, is distinguished by its high concentration of D-borneol, also known as " plant gold" due to its significant value. The essential oil extracted from this variant,rich in monoterpenes and sesquiterpenes, demonstrates a broad spectrum of pharmacological activities, including analgesic, antiinflammatory, antioxidant, cognition-enhancing, anti-bacterial, and insecticidal effects. These properties, underscored by extensive research, highlight the oil's potential in the biomedical, chemical, and food sectors as a valuable commodity. Nonetheless, the safety profile of this valuable oil remains poorly characterized, with its chemical composition and therapeutic efficacy subject to variations in the factors like geographic origin, harvesting timing, part used for extraction, and processing techniques. Such variability poses challenges to its clinical application and hampers the efficient exploitation of this resource. This review synthesizes current studies on C. camphora chvar. borneol essential oil and provides a detailed examination of its chemical and pharmacological profiles. In this study, we discuss existing research gaps and propose strategies for advancing its clinical use and industrial application, aiming to provide a foundational reference for future investigations and the resolution of its commercial and therapeutic challenges.

Morphological and phylogenetic analyses reveal four species of myxomycetes new to China.

Four species of myxomycetes (Arcyria pseudodenudata, Diderma europaeum, Lycogala irregulare, and Trichia armillata) new to China were observed via light microscope and scanning electron microscope, and detailed descriptions and illustrations are provided, along with comparisons with related species. Among them, A. pseudodenudata was discovered for the first time outside of the type locality, D. europaeum was discovered for the first time outside of Europe, and L. irregulare and T. armillata were reported again after being named. Phylogenetic analyses based on nuclear 18S rDNA and elongation factor-1 alpha sequences or nuclear 18S rDNA and cytochrome oxidase subunit I sequences was performed to provide a molecular basis for morphological identification. These specimens were deposited in the Herbarium of Fungi of Nanjing Normal University.

Predictive value of tumor-infiltrating lymphocytes for neoadjuvant therapy response in triple-negative breast cancer: A systematic review and meta-analysis.

BACKGROUND: The association between tumor-infiltrating lymphocyte (TIL) levels and the response to neoadjuvant therapy (NAT) in patients with triple-negative breast cancer (TNBC) remains unclear. AIM: To investigate the predictive potential of TIL levels for the response to NAT in TNBC patients. METHODS: A systematic search of the National Center for Biotechnology Information PubMed database was performed to collect relevant published literature prior to August 31, 2023. The correlation between TIL levels and the NAT pathologic complete response (pCR) in TNBC patients was assessed using a systematic review and meta-analysis. Subgroup analysis, sensitivity analysis, and publication bias analysis were also conducted. RESULTS: A total of 32 studies were included in this meta-analysis. The overall meta-analysis results indicated that the pCR rate after NAT treatment in TNBC patients in the high TIL subgroup was significantly greater than that in patients in the low TIL subgroup (48.0% vs 27.7%) (risk ratio 2.01; 95% confidence interval 1.77-2.29; P < 0.001, I 2 = 56%). Subgroup analysis revealed that the between-study heterogeneity originated from differences in study design, TIL level cutoffs, and study populations. Publication bias could have existed in the included studies. The meta-analysis based on different NAT protocols revealed that all TNBC patients with high levels of TILs had a greater rate of pCR after NAT treatment in all protocols (all P ≤ 0.01), and there was no significant between-protocol difference in the statistics among the different NAT protocols (P = 0.29). Additionally, sensitivity analysis demonstrated that the overall results of the meta-analysis remained consistent when the included studies were individually excluded. CONCLUSION: TILs can serve as a predictor of the response to NAT treatment in TNBC patients. TNBC patients with high levels of TILs exhibit a greater NAT pCR rate than those with low levels of TILs, and this predictive capability is consistent across different NAT regimens.

Substrate Characterization for Hydrolysis of Multiple Types of Aromatic Esters by Promiscuous Aminopeptidases.

Synthetic aromatic esters, widely employed in agriculture, food, and chemical industries, have become emerging environmental pollutants due to their strong hydrophobicity and poor bioavailability. This study attempted to address this issue by extracellularly expressing the promiscuous aminopeptidase (Aps) from Pseudomonas aeruginosa GF31 in B. subtilis, achieving an impressive enzyme activity of 13.7 U/mg. Notably, we have demonstrated, for the first time, the Aps-mediated degradation of diverse aromatic esters, including but not limited to pyrethroids, phthalates, and parabens. A biochemical characterization of Aps reveals its esterase properties and a broader spectrum of substrate profiles. The degradation rates of p-nitrobenzene esters (p-NB) with different side chain structures vary under the action of Aps, showing a preference for substrates with relatively longer alkyl side chains. The structure-dependent degradability aligns well with the binding energies between Aps and p-NB. Molecular docking and enzyme-substrate interaction elucidate that hydrogen bonding, hydrophobic interactions, and π-π stacking collectively stabilize the enzyme-substrate conformation, promoting substrate hydrolysis. These findings provide new insights into the enzymatic degradation of aromatic ester pollutants, laying a foundation for the further development and modification of promiscuous enzymes.

Chiral Co-Assembly with Narrowband Multi-Resonance Characteristics for High-Performance Circularly Polarized Organic Light-Emitting Diodes.

A promising kind of ternary chiral co-assemblies with high PLQY, large dissymmetry factor (glum), and narrowband multi-resonance characteristics are achieved by codoped-thermal annealing treatments of achiral luminescent polymer F8BT, chiral inducers R/S-5011, and achiral FRET acceptor DBN-ICZ. The optimized co-assemblies (F8BT)0.9-(R/S-5011)0.1-(DBN-ICZ)0.005 display narrowband yellow emission with full-width half maximum (FWHM) of 37 nm, PLQY of 79%, and intense CPL signals with |glum| of up to 0.26. Meaningfully, solution-processed CP-OLEDs by using those ternary chiral co-assemblies as emitting layer are successfully fabricated, which display yellow circularly polarized electroluminescence (CPEL) with EQEmax of 4.6% and gEL of up to 0.16. The corresponding Q-factor could reach up to 7.36 × 10-3, which is the highest of all the reported CP-OLEDs. Moreover, the devices also exhibit excellent comprehensive device performance with low Von of 7.0 V, high Lmax of about 25 000 cd m-2, extremely low efficiency roll-off with EQE of 4.3% at 10 000 cd m-2, as well as narrowband EL with FWHM of only 39 nm. The proposed ternary co-assembly strategy in fabricating CP-OLED provides the possibility to achieve high comprehensive device performance such as balancing high EQE and large gEL value, as well as narrowband emission, high brightness and low efficiency roll-off simultaneously.

Correlation of cTfh cells and memory B cells with AMR after renal transplantation.

Renal transplantation is the preferred treatment option for patients with end-stage renal disease (ESRD) in a clinical setting. Antibody mediated rejection (AMR) is one of the leading causes of graft dysfunction. To address the current shortcomings in the early diagnosis and treatment of AMR in clinical practice, this article analyzes the distribution of different circulating T follicular helper (cTfh) cell subtypes and B cell subpopulations in peripheral blood and detects the cytokine levels of chemokine ligand 13 (CXCL13), interleukin-21 (IL-21), and interleukin-4 (IL-4) related to cTfh cells in peripheral blood of kidney transplant recipients. Moreover, we also explore the correlation between cTfh cells, peripheral blood memory B cells, and AMR, their value as early predictive indicators of AMR, and explore potential therapeutic targets for AMR patients. Our results indicate that the proportion of cTfh cells increased at the onset of AMR, which plays an important role in antigen-specific B-cell immune regulation. Activation of cTfh cells in AMR patients correlates with phenotypes of memory B cells and plasma blasts. cTfh cells and memory B cells have promising diagnostic efficacies and predictive values for AMR. The proportion of cTfh cells to CD4+ T cells and the proportion of memory B cells to CD19+ B cells are correlated with serum creatinine levels, indicating that cTfh cells and memory B cells may be involved in the progression of AMR. In addition, the CXCL13, IL-21, and IL-4, which were associated with cTfh cells, may be involved in the onset of AMR.

Quantum criticality of generalized Aubry-André models with exact mobility edges using fidelity susceptibility.

In this study, we explore the quantum critical phenomena in generalized Aubry-André models, with a particular focus on the scaling behavior at various filling states. Our approach involves using quantum fidelity susceptibility to precisely identify the mobility edges in these systems. Through a finite-size scaling analysis of the fidelity susceptibility, we are able to determine both the correlation-length critical exponent and the dynamical critical exponent at the critical point of the generalized Aubry-André model. Based on the Diophantine equation conjecture, we can determines the number of subsequences of the Fibonacci sequence and the corresponding scaling functions for a specific filling fraction, as well as the universality class. Our findings demonstrate the effectiveness of employing the generalized fidelity susceptibility for the analysis of unconventional quantum criticality and the associated universal information of quasiperiodic systems in cutting-edge quantum simulation experiments.

Taxonomy and phylogeny of three species in Perichaena sensu lato (Myxomycetes = Myxogastria) from China.

After Gulielmina was erected and Ophiotheca was resurrected based on some species originally included in Perichaena (Trichiaceae, Trichiales, Myxomyxetes), some specimens from the Herbarium of Fungi of Nanjing Normal University previously identified as Perichaena species were reexamined from morphological and two-gene (nuclear 18S rDNA and elongation factor-1 alpha) phylogenetic perspectives. In this study, two new myxomycete species, Gulielmina subreticulospora and Ophiotheca dictyospora, are described. Gulielmina subreticulospora shows the following character combination: branched plasmodiocarps, single peridium with circular protrusions in the inner surface, capillitium (2.4-)2.8-3.0(-3.4) µm in diameter, spores (7.4-)8.0-8.5(-9.0) µm in diameter and sub-reticulated. Ophiotheca dictyospora shows the following character combination: sessile sporocarps to short plasmodiocarps, single peridium with a densely irregular network and protrusions in the inner surface, capillitium (2.7-)3.5-5.0(-7.1) µm in diameter, uneven, decorated with spines of uneven size, spores (7.7-)8.2-8.6(-9.4) µm in diameter including obviously complete cristate reticulation with serrated edges, with deep and clear grids. Both new taxa were compared with related species and their genetic isolation was statistically tested. Moreover, a comprehensive morphological description and a detailed figure plate are provided for Perichaena verrucifera, and its phylogenetic position is determined.

Mining of neurological adverse events associated with valbenazine: A post-marketing analysis based on FDA adverse event reporting system.

PURPOSE: Valbenazine is commonly used to treat tardive dyskinesia, and we conducted a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate neurological safety signals associated with valbenazine. METHODS: Data was collected in FAERS from the second quarter of 2017 to the fourth quarter of 2023 for data cleaning. Neurological adverse event (AE) signals of valbenazine were mined by calculating reporting odds ratios (ROR), information component (IC) and empirical Bayesian geometric mean (EBGM). The serious and non-serious cases and signals were prioritized using a rating scale. RESULTS: The number of neurological AE reports where the primary suspect (PS) drug was 8981 for valbenazine. Significant AE signals were identified by the preferred term (PT) analysis for valbenazine, including somnolence (ROR 19.69), tremor (ROR 15.17), and tardive dyskinesia (ROR 236.91), among which 18 AEs were identified as new signals. Patient age (p < 0.009) and sex (p = 0.197) might be associated with an increased risk of neurological AE severity. Notably, the association between valbenazine and neurological disorders remained when stratified by sex, age, and reporter type. AE timing analysis was performed for the drug and four moderate clinical priority signals [i.e., somnolence, balance disorder, parkinsonism, and akathisia (priorities 7)], showing the same early failure type profiles. CONCLUSIONS: The increase in neurological safety signals is identified in the post-marketing research of valbenazine. Clinicians need to pay attention to not only common AEs but also be alert to new neurological AE signals when using valbenazine.

Echinatin suppresses cutaneous squamous cell carcinoma by targeting GSTM3-mediated ferroptosis.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers for which effective drugs are urgently needed. Echinatin, a natural compound extracted from Glycyrrhiza plants, has shown promising antitumour effects. However, the efficacy and the direct target of echinatin in cSCC remain unclear. PURPOSE: This study conducted a systematic investigation of the antitumour effects of echinatin on cSCC and the underlying mechanisms involved. STUDY DESIGN AND METHODS: Three cSCC cell lines, a xenograft model, and a UV-induced cSCC mouse model were used to investigate the potential protective effects of echinatin. The interactions between echinatin and glutathione S-transferase mu3 (GSTM3) and between echinatin and peroxiredoxin-2 (PRDX2) were evaluated by a proteome microarray assay, pull-down LC‒MS/MS analysis, surface plasmon resonance, and molecular docking. The potential mechanisms of GSTM3-mediated echinatin activity were analysed by using western blotting, lentivirus infection and small interfering RNA (siRNA) transfection. RESULTS: In this study, we found that echinatin inhibited the proliferation and migration of cSCC cells but had no cytotoxic effect on primary human keratinocytes. Furthermore, echinatin significantly inhibited tumour growth in vivo. Mechanistically, our data showed that echinatin could directly bind to GSTM3 and PRDX2. Notably, echinatin inhibited GSTM3 and PRDX2 levels by promoting their proteasomal degradation, which led to the disruption of ROS production. We then revealed that echinatin increased mitochondrial ROS production by inhibiting GSTM3. Moreover, echinatin triggered ferroptosis by inhibiting GSTM3-mediated ferroptosis negative regulation (FNR) proteins. In addition, echinatin regulated GSTM3-mediated ROS/MAPK signalling. CONCLUSION: Echinatin has good antitumour effects both in vitro and in vivo. Moreover, our findings indicate that GSTM3 and PRDX2 could function as viable targets of echinatin in cSCC. Consequently, echinatin represents a novel treatment for cSCC through the targeting of GSTM3-mediated ferroptosis.