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Heat stress poses a significant threat to grain yield. Our previous study identified TT1, which encodes an α2 subunit of the 26S proteasome, as a critical regulator for rice heat tolerance, representing the first cloned QTL for crop heat tolerance. However, the mechanisms mediated by TT1 still remained elusive. In this study, we unveil SUMO-conjugating enzyme 1 (SCE1), which interacts with TT1 and acts as a downstream component of TT1, engaging in the TT1-mediated 26S proteasome degradation. SCE1 functions as a negative regulator of heat tolerance and can be linked to ubiquitination modification. Additionally, we observed that sHSPs such as Hsp24.1 and Hsp40 can undergo SUMOylation mediated by SCE1, leading to increased accumulation of sHSPs in the absence of SCE1. Furthermore, we propose that the global SUMOylation modulated by SCE1 serves as a crucial signal in response to heat stress, and the rapid decline in elevated SUMOylation is considered a positive effect to enhance heat tolerance due to the loss of SCE1 gene function. Reducing protein levels of SCE1 significantly enhanced grain yield under high-temperature stress by improving seed-setting rate and rice grain filling capacity. Our results uncover the critical role of SCE1 in TT1-mediated heat tolerance pathway, regulating the abundance of sHSP proteins and SUMOylation, and ultimately impacting rice heat tolerance. These findings underscore the significant potential of the TT1-SCE1 module in improving the heat tolerance of crops., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Mn-based layered oxide cathodes have attracted widespread attention due to high capacity and low cost, however, poor air stability, irreversible phase transitions, and slow kinetics inhibit their practical application. Here, we propose a universal interfacial reconstruction strategy based on converting residual alkali to tunnel phase Na 0.44 MnO 2 for addressing the above mentioned issue simultaneously, using O3 NaNi 0.4 Fe 0.2 Mn 0.4 O 2 @2 mol % Na 0.44 MnO 2 (NaNFM@NMO) as the prototype material. The optimized material exhibits an initial capacity and energy density comparable with lithium-ion batteries. The reversible anionic redox behavior and charge compensation mechanism of NaNFM@NMO were analyzed and verified by soft X-ray absorption spectrum and in situ X-ray absorption spectrum. Due to the intrinsic stability of the tunnel structure, excellent air stability and highly reversible structure evolution of the NaNFM@NMO cathode material are achieved, which are confirmed by contact angle test, rigorous aging test, and in situ X-ray diffraction. More importantly, the NaNFM@NMO cathode demonstrates a great match with the nonpresodiated hard carbon anode and shows excellent electrochemical performance of the full cell. Additionally, such a strategy could be also applied to modify P2-type cathodes, showing superior universality and good prospects in industrialized production. Overall, the proposed strategy could improve air stability while remaining interfacial and bulk stable simultaneously and will open up a whole new field for the optimization of other electrode materials.

Spermatogonial stem cells (SSCs) play crucial roles in the preservation of male fertility. However, successful ex vivo expansion of authentic human SSCs remains elusive due to the inadequate understanding of SSC homeostasis regulation. Using rhesus monkeys (Macaca mulatta) as a representative model, we characterized SSCs and progenitor subsets through single-cell RNA sequencing using a cell-specific network approach. We also profiled chromatin status and major histone modifications (H3K4me1, H3K4me3, H3K27ac, H3K27me3 and H3K9me3), and subsequently mapped promoters and active enhancers in TSPAN33+ putative SSCs. Comparing the epigenetic changes between fresh TSPAN33+ cells and cultured TSPAN33+ cells (resembling progenitors), we identified the regulatory elements with higher activity in SSCs, and the potential transcription factors and signaling pathways implicated in SSC regulation. Specifically, TGF-β signaling is activated in monkey putative SSCs. We provided evidence supporting its role in promoting self-renewal of monkey SSCs in culture. Overall, this study outlines the epigenetic landscapes of monkey SSCs and provides clues for optimization of the culture condition for primate SSCs expansion., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Although various antibacterial strategies have been developed, antibiotic chemotherapy remains the primary clinical treatment for bacterial infections. To address the limitations associated with the traditional antibiotic therapy, like burst drug release, rapid drug clearance, and the emergence of drug resistance, it is highly desirable to develop drug release systems that can realize controlled and sustained drug release to enhance the therapeutic efficacy. Herein, we present a novel drug release system, CIP@SU-102, which shows superior and long-lasting antibacterial activity. CIP@SU-102 was readily fabricated by the encapsulation of ciprofloxacin (CIP), a cationic broad-spectrum antibiotic, into an anionic Zr-based metal-organic framework SU-102 through ion-exchange. Notably, the loading capacity and efficiency of CIP were impressively high, reaching 33.3% and 66.8%, respectively. In vitro assays demonstrated that CIP@SU-102 has superior and prolonged antimicrobial activity against Gram-negative ( Escherichia coli ) and Gram-positive ( Staphylococcus aureus ) bacteria, including the methicillin-resistant Staphylococcus aureus (MRSA). Remarkably, CIP@SU-102 could retain its antibacterial efficacy even after continuous drug release for 20 days. In vivo assays verified that CIP@SU-102 could significantly accelerate infected wound healing because of its sustained drug release properties. Due to the low cost and biocompatibility of SU-102 as well as the affordability of ciprofloxacin, CIP@SU-102 is a very promising antibacterial agent for long-lasting bacterial disinfection and boosting infected wound healing in actual clinical applications. This work highlights the potential of the metal-organic framework-based drug release systems for sustained antimicrobial therapy.

Objective: To explore the association between doctors' abusive supervision and patients' deviant behavior, and to evaluate the mediating role of patients' negative emotion., Methods: A cross-sectional study with a convenient sample was conducted among hospitalized patients from April 13 to May 23, 2022, at a medical center in Taizhou, China. A total of 923 hospitalized patients participated in this survey. Collected data was analyzed based on correlation analyses and mediation regression approach., Results: The findings showed that inpatients who think they experienced abusive supervision from their doctors exhibited higher negative emotion and were more likely to engage in both interpersonal and organizational deviance. In addition, the higher negative emotion the inpatients had, the more likely they would take deviant behavior. Of note, patients' negative emotion served as a mediator between doctors' abusive supervision and patients' deviant behavior., Conclusion: Both doctors' abusive supervision and patients' negative emotion were found to be significantly correlated with patients' deviant behavior, with negative emotion playing a mediating role between abusive supervision and deviance. This finding will be helpful for studying the doctor-patient relationship., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Luo et al.)

Background: Cyclic GMP-AMP synthase (cGAS) is widely acknowledged for detecting cytosolic chromatin fragments and triggering innate immune responses through the production of the second messenger cGAMP, which subsequently activates the adaptor protein STING. However, the role of cGAS in regulating metabolic reprogramming independently of STING activation has not yet been explored., Methods: Gene set enrichment pathway analysis (GSEA) based on TCGA transcriptomics, combined with Seahorse metabolic analysis of CRC cell lines and human normal colonic mucosa cell line FHC, was performed to profile the metabolic features in CRC. cGAS doxycycline- (dox) inducible knockout (iKO) CRC sublines were generated to investigate the role of cGAS in CRC. Transcriptome and proteome data from COAD cohorts were utilized to evaluate the RNA and protein expression levels of cGAS in COAD tissues and normal colon tissues. Overall survival information of patients with COAD was used to evaluate the prognostic value of cGAS expression. Colony formation assays were conducted to evaluate the clonogenicity of CRC cells under different situations. Flow cytometry detecting the signal of fluorogenic reactive oxygen species (ROS) probes was performed to evaluate the total cellular and mitochondrial oxidative stress level in CRC cells. A propidium iodide (PI) staining assay was used to evaluate the cell death level in CRC cells. Quantitative PCR (qPCR) was conducted to detect the RNA level of STING pathway downstream target genes. Mass spectrometry was used for the identification of novel binding partners of cGAS in CRC cells. Co-immunoprecipitation (co-IP) was conducted to confirm the interaction between cGAS and NDUFA4L2., Results: By integrating metabolic pathway analysis based on TCGA transcriptomics with Seahorse metabolic analysis of a panel CRC cell lines and the human normal colonic mucosa cell line FHC, we demonstrated that CRC cells exhibit typical characteristics of metabolic reprogramming, characterized by a shift from oxidative phosphorylation (OXPHOS) to glycolysis. We found that cGAS is critical for CRC cells to maintain this metabolic switch. Specifically, the suppression of cGAS through siRNA-mediated knockdown or doxycycline-inducible knockout reversed this metabolic switch, resulting in increased OXPHOS activity, elevated production of OXPHOS byproduct reactive oxygen species (ROS), and consequently caused oxidative stress. This disruption induced oxidative stress, ultimately resulting in cell death and reduced cell viability. Moreover, significant upregulation of cGAS in CRC tissues and cell lines and its association with poor prognosis in CRC patients was observed. Subsequently, we demonstrated that the role of cGAS in regulating metabolic reprogramming does not rely on the canonical cGAS-STING pathway. Co-immunoprecipitation combined with mass spectrometry identified NDUFA4L2 as a novel interactor of cGAS. Subsequent functional experiments, including mitochondrial respiration and oxidative stress assays, demonstrated that cGAS plays a crucial role in sustaining elevated levels of NDUFA4L2 protein expression. The increased expression of NDUFA4L2 is essential for cGAS-mediated regulation of metabolic reprogramming and cell survival in CRC cells., Conclusion: cGAS regulates metabolic reprogramming and promotes cell survival in CRC cells through its interaction with NDUFA4L2, independently of the canonical cGAS-STING pathway., Competing Interests: Declaration of competing interest The authors declare that they do not have competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Background: A series of multi-sensory interventions are proved to be effective in reducing pain among premature infants. Nevertheless, there lacks a comparison of these interventions to find the most suitable and optimal one for clinical decision-making., Objective: This systematic review and network meta-analysis aims to compare the effectiveness of various multi-sensory interventions, and to identify the optimal intervention for alleviating pain in premature infants., Methods: A comprehensive literature search was performed on August 19, 2024 to identify pertinent clinical trials. The Cochrane Risk of Bias (version 2) was used to assess the quality and potential bias of each included study. Network meta-analysis was used to assess the effectiveness of various interventions and to identify the optimal ones., Results: A total of 18 clinical trials involving 1408 premature infants were included. Three multi-sensory interventions were shown to be superior to routine practice in reducing pain among premature infants, including tactile-kinesthetic intervention, tactile-auditory intervention and tactile-visual-gustatory-olfactory intervention (all, P < 0.05). Among these interventions, tactile-kinesthetic intervention ranks the best for its effectiveness in alleviating procedural pain among premature infants. Subgroup network meta-analysis demonstrated that the tactile-visual-gustatory-auditory-olfactory intervention ranked the best for its effectiveness in reducing pain from invasive procedures, with the tactile-auditory intervention best for non-invasive procedures., Conclusions: Our study suggests that cautious assessment and identification should be prioritized to select appropriate multi-sensory interventions based on pain procedures, thus to effectively reduce pain in premature infants. Subsequent studies are needed to refine and optimize these strategies for broader application., Prospero Registry: CRD42024510352., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Deep-UV, (wavelength λ < 200 nm) nonlinear-optical (NLO) silicate crystals have long been troubled by weak second-harmonic-generation (SHG) effect and common non-phase-matchability, leading to the stagnation of silicate research, despite abundant reserves of silicates on the earth. Representative and simple α-SiO 2 is an ideal structural prototype toward improving silicate NLO performance by exploring efficient strategies. Herein, through two-step structural modulations based on fundamental "distortion and superposition" principles of NLO response, two deep-UV NLO crystals taking α-SiO 2 as a structural template, Na 2 BeSiO 4 and Li 2 BeSiO 4 , are synthesized successively. By providing flexible coordination BeO 4 tetrahedra for rigid tetrahedral SiO 4 that induces distortion of SiO 4 , Na 2 BeSiO 4 achieves significant enhancement of phase-matchable SHG effect of 15 × α-SiO 2 . Further, by introducing a low coordination number of Li + cations that stimulates uniform orientation of SiO 4 , Li 2 BeSiO 4 exhibits the strongest phase-matchable SHG effect as large as 40 × α-SiO 2 among the universal SiO 4 -governed NLO silicates. Also, computational investigations support the rationality of the structural modulations well. Such efficient structural modulations can greatly promote the exploration and rational design of NLO silicates., (© 2024 Wiley‐VCH GmbH.)

Background: The objective of this study was to perform a comprehensive pooled analysis aimed at comparing the efficacy and safety of robot-assisted partial nephrectomy (RAPN) between completely endophytic tumors (CERT) and non-completely endophytic tumors (non-CERT)., Methods: This study adhered rigorously to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct a systematic review and meta-analysis. We performed a systematic search in the PubMed, Embase, Web of Science, and Cochrane Library databases, focusing on studies published in English up to May 2024. Our analysis primarily evaluated key outcomes, specifically perioperative, functional, and oncological outcomes., Results: A total of 2126 patients across six studies were included in the analysis. Compared to non-CERT, CERT was associated with significantly higher rates of major complications (Odds Ratio [OR]: 2.47; 95% CI: 1.14 to 5.34; p = 0.02), longer warm ischemia times (Weighted Mean Difference [WMD]: 3.27 min; 95% CI: 0.61 to 5.39; p = 0.02), a greater decline in estimated glomerular filtration rate (eGFR) (WMD: 2.93 ml/min/1.73 m 2 ; 95% CI: 0.75 to 5.11; p = 0.008), and relatively lower trifecta achievement rates (OR: 0.63; 95% CI: 0.41 to 0.96; p = 0.03). However, no statistically significant differences were observed between the two groups in terms of operative time, length of stay, blood loss, transfusion rates, intraoperative complications, overall complications, positive surgical margins, and local recurrence., Conclusions: Although CERT was associated with greater declines in eGFR and lower rates of trifecta achievement, it yielded perioperative, functional, and oncologic outcomes comparable to those of non-CERT in RAPN. Our findings suggest that RAPN for completely endophytic renal masses can achieve acceptable outcomes when performed in centers with substantial expertise in robotic surgery., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=555067, identifier CRD42024555067., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gu, Lv, Liu and Wang.)

Multi-drug therapies are common in cardiovascular disease intervention; however, io channel/pump coordination has not been tested electrophysiologically. Apparently, inward currents were not elicited by Yoda1/10 nM or Dobutamine/100 nM alone in Ah-type baroreceptor neurons, but were by their combination. To verify this, electroneurography and the whole-cell patch-clamp technique were performed. The results showed that Ah- and C-volley were dramatically increased by the combination at 0.5 V and 5 V, in contrast to A-volley, as consistent with repetitive discharge elicited by step and ramp with markedly reduced current injection/stimulus intensity. Notably, a frequency-dependent action potential (AP) duration was increased with Iberiotoxin-sensitive K + component. Furthermore, an increased peak in AP measured in phase plots suggested enhanced Na + influx, cytoplasmic Ca 2+ accumulation through reverse mode of Na + /Ca 2+ exchanger, and, consequently, functional KCa1.1 up-regulation. Strikingly, the Yoda1- or Dbtm-mediated small/transient Na + /K + -pump currents were robustly increased by their combination, implying a quick ion equilibration that may also be synchronized by hyperpolarization-induced voltage-sag, enabling faster repetitive firing. These novel findings demonstrate multi-channel/pump collaboration together to integrate neurotransmission at the cellular level for baroreflex, providing an afferent explanation in sexual dimorphic blood pressure regulation, and raising the caution regarding the individual drug concentration in multi-drug therapies to optimize efficacy and minimize toxicity.

High Al content (60%) p-AlGaN with different NH 3 flow rates was grown using metal-organic chemical vapor deposition (MOCVD), and changes in its photoelectric properties were studied using the Hall effect tester (Hall) and cathodoluminescence (CL) spectrometer. The results show that the film resistivity increases from 3.8   Ω·cm to 46.5   Ω·cm with increasing NH 3 flow rate. The impurity peak intensity of p-AlGaN grown under high NH 3 flow conditions is particularly high, indicating numerous point defects. The results of high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) show a large number of Ga interstitial atoms (Ga i ) at the interface. As Ga i acts as a donor, this may be the main reason for the increase in resistivity. And under high NH 3 flow conditions, a lattice distortion and a high density of dislocation occur between p-AlGaN and p-GaN, which can lead to enhanced carrier scattering and decreased mobility. Additional validation via LED growth experiments indicates that the luminescence intensity of samples with low ammonia concentration increased by more than 13000 times.

Iron deficiency in pregnancy remains underdiagnosed despite professional society recommendations for first-trimester complete blood count (CBC) screening. To determine the effectiveness of the CBC hemoglobin and mean corpuscular volume (MCV) to identify iron deficiency in pregnancy, we conducted a retrospective analysis of 20,550 pregnancies from 2009 to 2022 at the University of California, San Francisco, obstetrics clinics. A total of 16,547 (80.5%) pregnant individuals had first-trimester screening CBC; 345 (2.1%) had a coincident ferritin test. Hemoglobin level less than 11 g/dL and MCV level less than 80 fL each had sensitivity of only 30% (95% CI, 20-41%) to detect first-trimester iron deficiency (ferritin level less than 30), corresponding to a negative likelihood ratio of 0.90 (95% CI, 0.77-1.05) and 0.85 (95% CI, 0.73-0.99), respectively. More than 50% of the 1,749 women with documented iron deficiency anytime during pregnancy were neither anemic nor microcytic at the time of diagnosis., Competing Interests: Financial Disclosure Andrew Leavitt serves on the advisory boards for hemophilia gene therapy for BioMarin and Pfizer. The other authors did not report any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The nanoscale multidrug codelivery system for synergistic therapy is an effective strategy for tumor treatment. However, the low drug delivery efficiency and poor therapeutic effects limit its application. Here, based on the coordination effect of Artemisinin (Art), quercetin (Qc), and Fe 3+ , we had constructed a safe and efficient carrier-free hyaluronic acid (HA)-modified Art-Fe-Qc nanoparticles (AFQ@HA NPs) for enhanced chemotherapy/photothermal therapy (PTT)-chemodynamic therapy (CDT) synergistic therapy, which achieved an ultrahigh drug loading efficiency and a multifunction anticancer strategy. The results showed that high drug loading was achieved based on drug coordination self-assembly, with Art and Qc contents of 38.6 and 42.7%, respectively. At the same time, based on the Qc-Fe coordination molecular network, the system had excellent photothermal conversion performance with an efficiency of 57.3% and could effectively inhibit the expression of HSP70, achieving enhanced PTT. Further, under the stimulation of excessive H 2 O 2 and glutathione (GSH) in the tumor microenvironment, the AFQ@HA NPs were continuously degraded, while releasing Art and Fe 3+ /Fe 2+ to achieve iron ion-enhanced CDT. The results of in vitro and in vivo experiments showed that AFQ@HA NPs could achieve chemotherapy-PTT-CDT synergistic therapy in response to tumor microenvironment by passively targeting and actively targeting tumor cells with CD44, demonstrating its excellent targeted antitumor effects.

Rice grain number is a crucial agronomic trait impacting yield. In this study, we characterized a quantitative trait locus (QTL), GRAIN NUMBER 1.1 (GN1.1), which encodes a Flowering Locus T-like1 (FT-L1) protein and acts as a negative regulator of grain number in rice. The elite allele GN1.1 B , derived from the Oryza indica variety, BF3-104, exhibits a 14.6% increase in grain yield compared with the O. japonica variety, Nipponbare, based on plot yield tests. We demonstrated that GN1.1 interacted with and enhanced the stability of ADP-ribosylation factor (Arf)-GTPase-activating protein (Gap), OsZAC. Loss of function of OsZAC results in increased grain number. Based on our data, we propose that GN1.1 B facilitates the elevation of auxin content in young rice panicles by affecting polar auxin transport (PAT) through interaction with OsZAC. Our study unveils the pivotal role of the GN1.1 locus in rice panicle development and presents a novel, promising allele for enhancing rice grain yield through genetic improvement., (© 2024 Institute of Botany, Chinese Academy of Sciences.)

Germinal matrix-intraventricular hemorrhage (GM-IVH) is a detrimental neurological complication that occurs in preterm infants, especially in babies born before 32 weeks of gestation and in those with a very low birth weight. GM-IVH is defined as a rupture of the immature and fragile capillaries located in the subependymal germinal matrix zone of the preterm infant brain, and it can lead to detrimental neurological sequelae such as posthemorrhagic hydrocephalus (PHH), cerebral palsy, and other cognitive impairments. PHH following GM-IVH is difficult to treat in the clinic, and no levelone strategies have been recommended to pediatric neurosurgeons. Several cellular and molecular mechanisms of PHH following GM-IVH have been studied in animal models, but no effective pharmacological strategies have been used in the clinic. Thus, a comprehensive understanding of molecular mechanisms, potential pharmacological strategies, and surgical management of PHH is urgently needed. The present review presents a synopsis of the pathogenesis, diagnosis, and cellular and molecular mechanisms of PHH following GM-IVH and explores pharmacological strategies and surgical management., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: This study aims to explore the effects of Triptolide (TP) on the differentiation of Th17 cells in ankylosing spondylitis (AS)., Methods: Peripheral blood mononuclear cells (PBMCs) collected from 10 patients with active AS patients were exposed to TP, GSK-J4 or vehicle. T lymphocyte subsets were analyzed using flow cytometry. ELISA was used to assess the level of IL-17. Western blot analysis and quantitative RT-PCR were used to measure the mRNA and protein levels of RORγt, JMJD3, EZH2, JAK2 and STAT3 in the JAK2/STAT3 signaling pathway., Results: We observed a tendency toward a greater percentage of IL-17-positive CD4+ T cells in peripheral blood mononuclear cells (PBMCs) from patients with active AS than in those from healthy controls. Triptolide (TP) and GSK-J4 significantly reduced IL-17 expression. In cultured PBMCs from patients with active AS, 24 h of treatment with TP or GSK-J4 decreased the expression of RORγt ( p  < 0.05), JAK2 and STAT3 (JAK2: p  < 0.05; STAT3: p  < 0.05). Furthermore, both triptolide and GSK-J4 increased the level of histone 3 with Lys 27 trimethylation (H3K27me3) in patient-derived PBMCs. H3K27me3 enrichment was detected at the promoters of the RORc, STAT3 and IL-17 genes. Consistent with this finding, triptolide upregulated the EZH2 gene and downregulated the JMJD3 gene., Conclusion: Triptolide inhibits Th17 cell differentiation via H3K27me3 upregulation and orchestrates changes in histone-modifying enzymes, including JMJD3 and EZH2. These findings support the clinical efficacy of triptolide for AS and may provide clues for identifying molecular targets for the development of novel treatments.

Mesophotic coral ecosystems (MCEs), located at depths ranging from 30-150 m, host some of the most diverse yet least explored marine bioresources, particularly significant for the discovery of new bioactive molecules. The fungus Beauveria sp. NBUF147, associated with an Irciniidae sponge from the mesophotic zone at a depth of 82 m, underwent chemical investigation that led to the identification of one new sterol, beautoide A (1), and one reported sterol, 3β,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (2). Their structures were determined from analysis of spectroscopic data and X-ray crystallography. Evaluation of biological activity in prednisolone-induced osteoporotic zebrafish showed that 1 was anti-osteoclastogenic in vivo at 3.0 μM., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Objective: Diabetic nephropathy (DN) is a serious complication that may occur during the later stages of diabetes, and can be further exacerbated by podocyte damage. Piperazine ferulate (PF) has well-defined nephroprotective effects and is used clinically in the treatment of chronic nephritis and other kidney diseases. However, the renoprotective effects and mechanisms of PF on DN are not clear. This study aims to investigate the protective effect of PF on DN and its mechanism of action, to inform the clinical application of PF in DN treatment. Methods: Network pharmacology was performed to predict the mechanism of action of PF in DN. Male Sprague Dawley rats were intraperitoneally injected with STZ (60 mg/kg) to establish a DN model, and then assessed for renal injury after 12 weeks of administration. In vitro , rat podocytes were treated with 25 mmol/L glucose and cultured for 24 h, followed by an assessment of cell injury. Results: Our results showed that PF significantly improved renal function, reduced renal pathological changes, decreased inflammatory response, and alleviated podocyte damage in DN rats. PF also attenuated glucose-induced podocyte injury in vitro . Regarding molecular mechanisms, our study demonstrated that PF downregulated the expression of genes and proteins related to AGE-RAGE-mediated inflammatory signaling. Conclusion: In summary, PF exerts its renoprotective effects by decreasing inflammation and protecting against podocyte injury through the inhibition of the AGE/RAGE/NF-κB/NLRP3 pathway. Overall, these data support the clinical potential of PF as a renoprotective agent in DN., Competing Interests: Author BL was employed by Chengdu Hanpharm Pharmaceutical Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Min, Xie, Jiang, Rui, Li, Zeng and Liu.)

Chronic kidney disease (CKD) is a type of chronic disease in which multiple factors are responsible for the structural and functional disorders of the kidney. Piperazine ferulate (PF) has anti-platelet and anti-fibrotic effects, and its mechanism of action remains to be elucidated. This study aimed to investigate the protective effect of PF against CKD in rats and to determine its mechanism of action. Network pharmacology was used to predict potential PF action targets in the treatment of CKD and to further validate them. A rat model of CKD was established; blood was collected, etc., for the assessment of the renal function; renal pathologic damage was examined using hematoxylin and eosin (HE) staining and Masson staining; changes in the levels of TGF-β1 and α-SMA were determined with ELISA; EPOR, FN, and COL I expression were detected utilizing immunohistochemistry; and HIF-1α, HIF-2α, and EPO protein molecules were analyzed deploying western blotting. PF reduces Scr, BUN, and 24 h UP levels; decreases FN and COL I expression; and attenuates renal injury. Additionally, PF inhibited TGF-β1 and stimulated the production of HIF-1α and HIF-2α, which downregulated α-SMA and upregulated EPO. PF attenuated the progression of the CKD pathology, and the mechanism of its action is possibly associated with the promotion of HIF-1α/HIF-2α/EPO production and TGF-β1 reduction., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sweet osmanthus (Osmanthus fragrans) is famous in China for its flowers and contains four groups: Albus, Luteus, Aurantiacus, and Asiaticus. Understanding the relationships among these groups and the genetic mechanisms of flower color and aroma biosynthesis are of tremendous interest. In this study, we sequenced representative varieties from two of the four sweet osmanthus groups. Multiomics and phylogenetic analyses of varieties from each of the four groups showed that Asiaticus split first within the species, followed by Aurantiacus and the sister groups Albus and Luteus. We show that the difference in flower color between Aurantiacus and the other three groups was caused by a 4-bp deletion in the promoter region of carotenoid cleavage dioxygenase 4 (OfCCD4) that leads to expression decrease. In addition, we identified 44 gene pairs exhibiting significant structural differences between the multiseasonal flowering variety "Rixianggui" in the Asiaticus group and other autumn-flowering varieties. Through correlation analysis between intermediate products of aromatic components and gene expression, we identified eight genes associated with the linalool and α- and β-ionone biosynthesis pathways. Overall, our study offers valuable genetic resources for sweet osmanthus, while also providing genetic clues for improving the flower color and multiseasonal flowering of osmanthus and other flowers., Competing Interests: Conflict of interest statement: The authors declare that they have no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Wheatgrass is recognized for its nutritional and medicinal properties, partly attributed to its flavonoid content. The objective of this study was to assess the flavonoid content and antioxidant properties of wheatgrass obtained from a wide range of 145 wheat cultivars, which included Chinese landraces (CL), modern Chinese cultivars (MCC), and introduced modern cultivars (IMC). The flavonoids were extracted using a solution of 80% methanol, and their content was evaluated using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). The results revealed the assessed cultivars showed significant variation in their total flavonoid content (TFC), with MCCs generally having higher amounts compared to CLs. PCA analysis demonstrated clear variations in flavonoid profiles between different cultivar groups, emphasizing the evolutionary inconsistencies in wheat breeding. The antioxidant assays, ABTS, DPPH, and FRAP, exhibited robust abilities for eliminating radicals, which were found to be directly associated with the amounts of flavonoids. In addition, this study investigated the correlation between the content of flavonoids and the ability to resist powdery mildew in a collection of mutated wheat plants. Mutants exhibiting heightened flavonoid accumulation demonstrated a decreased severity of powdery mildew, suggesting that flavonoids play a protective role against fungal infections. The results highlight the potential of wheatgrass as a valuable source of flavonoids that have antioxidant and protective effects. This potential is influenced by the genetic diversity and breeding history of wheatgrass. Gaining insight into these connections can guide future wheat breeding endeavors aimed at improving nutritional value and in strengthening disease resistance. The current finding provides critical information for developing wheatgrass with high flavonoid content and antioxidant activity.

Background: The canine influenza virus (CIV) outbreak has garnered considerable attention as it poses a significant threat to dog health. During the H3N2 CIV evolution in beagles, the virus formed a new clade after 2019 and gradually became more adaptable to other mammals. Therefore, successfully elucidating the biological characteristics and constructing a canine influenza infection model is required for CIV characterization., Methods: We performed genetic analyses to examine the biological characteristics and infection dynamics of CIV., Results: The genotype of our H3N2 CIV strain (from 2019 in Shanghai) belonged to the 5.1 clade, which is now prevalent in China. Using MDCK cells, we investigated viral cytopathic effects. Virus size and morphology were observed using transmission electron microscopy. Beagles were also infected with 10 4 , 10 5 , and 10 6 50% egg-infectious doses (EID 50 ). When compared with the other groups, the 10 6 EID 50 group showed the most obvious clinical symptoms, the highest virus titers, and typical lung pathological changes. Our results suggested that the other two treatments caused mild clinical manifestations and pathological changes. Subsequently, CIV distribution in the 10 6 EID 50 group was detected by hematoxylin and eosin (H&E) and immunofluorescence (IF) staining, which indicated that CIV primarily infected the lungs., Conclusions: The framework established in this study will guide further CIV prevention strategies., (© 2024. The Author(s).)

We established experimental models of manganese (Mn) and iron (Fe) exposure in vitro and in vivo, and addressed the effects of manganese and iron combined exposure on the synaptic function of pheochromocytoma derived cell line 12 (PC12) cells and rat cortex, respectively. We investigated the protective effect of sodium para-aminosalicylate (PAS-Na) on manganese and iron combined neurotoxicity, providing a scientific basis for the prevention and treatment of ferromanganese combined neurotoxicity. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of protein and mRNA related to synaptic damage. Y-maze novelty test and balance beam test were used to evaluate the motor and cognitive function of rats. Haematoxylin and eosin (H&E) and Nissl staining were performed to observe the cortical damage of rats. The results showed that the combined exposure of Mn and Fe in rats led to a synergistic effect, attenuating growth and development, and altering learning and memory as well as motor function. The combination of Mn and Fe also caused damage to the synaptic structure of PC12 cells, which is manifested as swelling of dendrites and axon terminals, and even lead to cell death. PAS-Na displayed some antagonistic effects against the Mn- and Fe-induced synaptic structural damage, growth, learning and memory impairment., (© 2024 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

Sodium para-aminosalicylic acid (PAS-Na) treatment for manganese (Mn) intoxication has shown efficacy in experimental and clinical studies, giving rise to additional studies on its efficacy for lead (Pb) neurotoxicity and its associated mechanisms of neuroprotection. The difference between PAS-Na and other metal complexing agents, such as edetate calcium sodium (CaNa 2 -EDTA), is firstly that PAS-Na can readily pass through the blood-brain barrier (BBB), and complex and facilitate the excretion of manganese and lead. Secondly, PAS-Na has anti-inflammatory effects. Recent studies have broadened the understanding on the mechanisms associated with efficacy of PAS-Na. The latter has been shown to modulate multifarious manganese- and lead- induced neurotoxicity, via its anti-apoptotic and anti-inflammatory effects, as well as its ability to inhibit pyroptosis, and regulate abnormal autophagic processes. These observations provide novel scientific bases and new concepts for the treatment of lead, mercury, copper, thallium, as well as other toxic encephalopathies, and implicate PAS-Na as a compound with greater prospects for clinical medical application., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Enhanced magnetic resonance imaging (MRI) is widely used in the diagnosis, treatment and prognosis of hepatocellular carcinoma (HCC), but it can not effectively reflect the heterogeneity within the tumor and evaluate the effect after treatment. Preoperative imaging analysis of voxel changes can effectively reflect the internal heterogeneity of the tumor and evaluate the progression-free survival (PFS)., Aim: To predict the PFS of patients with HCC before operation by building a model with enhanced MRI images., Methods: Delineate the regions of interest (ROI) in arterial phase, portal venous phase and delayed phase of enhanced MRI. After extracting the combinatorial features of ROI, the features are fused to obtain deep learning radiomics (DLR)&#95;Sig. DeLong's test was used to evaluate the diagnostic performance of different typological features. K-M analysis was applied to assess PFS in different risk groups, and the discriminative ability of the model was evaluated using the C-index., Results: Tumor diameter and diolame were independent factors influencing the prognosis of PFS. Delong's test revealed multi-phase combined radiomic features had significantly greater area under the curve values than did those of the individual phases ( P < 0.05).In deep transfer learning (DTL) and DLR, significant differences were observed between the multi-phase and individual phases feature sets ( P < 0.05). K-M survival analysis revealed a median survival time of high risk group and low risk group was 12.8 and 14.2 months, respectively, and the predicted probabilities of 6 months, 1 year and 2 years were 92%, 60%, 40% and 98%, 90%,73%, respectively. The C-index was 0.764, indicating relatively good consistency between the predicted and observed results. DTL and DLR have higher predictive value for 2-year PFS in nomogram., Conclusion: Based on the multi-temporal characteristics of enhanced MRI and the constructed Nomograph, it provides a new strategy for predicting the PFS of transarterial chemoembolization treatment of HCC., Competing Interests: Conflict-of-interest statement: The authors declare that there are no competing interests associated with the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

A pair of water-stable and highly porous homochiral fluorescent silver-organic framework enantiomers, namely, R -Ag-BPA-TPyPE ( R - 1 ) and S -Ag-BPA-TPyPE ( S - 1 ), had been prepared as enantioselective fluorescence sensors. Combining homochiral 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BPA) with an AIE-based ligand tetrakis[4-(pyridin-4-yl)phenyl]ethene (TPyPE) in complexes R - 1 and S - 1 made them possess favorable circularly polarized luminescence (CPL) properties, and their CPL spectra were almost mirror images of each other. The luminescence dissymmetry factors ( g lum ) are ±2.2 × 10 -3 for R - 1 and S - 1, and the absolute fluorescence quantum yields (Φ Fs ) are 32.0% for R - 1 and S - 1 , respectively. Complex R - 1 could enantioselectively recognize two enantiomers of amino acids in water or DMF with high Stern-Volmer constants of 236-573 M -1 and enantioselectivity ratios of 1.40-1.78.

Aim: To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy (DR) and in patients with or without diabetic macular edema (DME)., Methods: The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study. The severity of DR patients was graded as mild, moderate and severe non-proliferative diabetic retinopathy (NPDR) according to the international clinical diabetic retinopathy (ICDR) disease severity scale classification, and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods. The presence of DME was determined by optical coherence tomography (OCT), and differences in vascular morphological characteristics were compared between patients with and without DME., Results: Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99% and a Dice metric of 0.76. Compared with the healthy group, the DR group had smaller vessel angles (33.68±3.01 vs 37.78±1.60), smaller fractal dimension (Df) values (1.33±0.05 vs 1.41±0.03), less vessel density (1.12±0.44 vs 2.09±0.36) and fewer vascular branches (206.1±88.8 vs 396.5±91.3), all P <0.001. As the severity of DR increased, Df values decreased, P =0.031. No significant difference between the DME and non-DME groups were observed in vascular morphological characteristics., Conclusion: In this study, an artificial intelligence retinal vessel segmentation system is used with 99% accuracy, thus providing with relatively satisfactory performance in the evaluation of quantitative vascular morphology. DR patients have a tendency of vascular occlusion and dropout. The presence of DME does not compromise the integral retinal vascular pattern., Competing Interests: Conflicts of Interest: Deng XY, None; Liu H, None; Zhang ZX, None; Li HX, None; Wang J, None; Chen YQ, None; Mao JB, None; Sun MZ, None; Shen LJ, None., (International Journal of Ophthalmology Press.)

High-voltage LiNi 0.5 Mn 1.5 O 4 (LNMO) is one of the most promising cathode candidates for rechargeable lithium-ion batteries (LIBs) but suffers from deteriorated cycling stability due to severe interfacial side reactions and manganese dissolution. Herein, a micro-nano porous spherical LNMO cathode was designed for high-performance LIBs. The disordered structure and the preferred exposure of the {111} facets can be controlled by the release of lattice oxygen in the high-temperature calcination process. The unique configuration of this material could enhance the structural stability and play a crucial role in inhibiting manganese dissolution, promoting the rapid transport of Li + , and reducing the volume strain during the charge/discharge process. The designed cathode exhibits a remarkable discharge capacity of 136.7 mA h g -1 at 0.5C, corresponding to an energy density of up to 636.4 W h kg -1 , unprecedented cycling stability (capacity retention of 90.6% after 500 cycles) and superior rate capability (78.9% of initial capacity at 10C). The structurally controllable preparation strategy demonstrated in this work provides new insights into the structural design of cathode materials for LIBs., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

The main metabolic product of the pyridinecarboxamide insecticide flonicamid, N-(4-trifluoromethylnicotinyl)glycinamide (TFNG-AM), has been shown to have very high mobility in soil, leading to its accumulation in the environment. Catabolic pathways of flonicamid have been widely reported, but few studies have focused on the metabolism of TFNG-AM. Here, the rapid transformation of TFNG-AM and production of the corresponding acid product N-(4-trifluoromethylnicotinoyl) glycine (TFNG) by the plant growth-promoting bacterium Variovorax boronicumulans CGMCC 4969 were investigated. With TFNG-AM at an initial concentration of 0.86 mmol/L, 90.70 % was transformed by V. boronicumulans CGMCC 4969 resting cells within 20 d, with a degradation half-life of 4.82 d. A novel amidase that potentially mediated this transformation process, called AmiD, was identified by bioinformatic analyses. The gene encoding amiD was cloned and expressed recombinantly in Escherichia coli, and the enzyme AmiD was characterized. Key amino acid residue Val154, which is associated with the catalytic activity and substrate specificity of signature family amidases, was identified for the first time by homology modeling, structural alignment, and site-directed mutagenesis analyses. When compared to wild-type recombinant AmiD, the mutant AmiD V154G demonstrated a 3.08-fold increase in activity toward TFNG-AM. The activity of AmiD V154G was greatly increased toward aromatic L-phenylalanine amides, heterocyclic TFNG-AM and IAM, and aliphatic asparagine, whereas it was dramatically lowered toward benzamide, phenylacetamide, nicotinamide, acetamide, acrylamide, and hexanamid. Quantitative PCR analysis revealed that AmiD may be a substrate-inducible enzyme in V. boronicumulans CGMCC 4969. The mechanism of transcriptional regulation of AmiD by a member of the AraC family of regulators encoded upstream of the amiD gene was preliminarily investigated. This study deepens our understanding of the mechanisms of metabolism of toxic amides in the environment, providing new ideas for microbial bioremediation., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This study was designed to assess the uptake heterogeneity in neuroendocrine tumor (NET) patients at initial diagnosis with dual-tracer PET imaging and the staging changes and prognostic value it brings to explore the indication of the use of dual-tracer PET., Methods: Fifty-one newly diagnosed patients with pathologically confirmed NET who underwent 18 F-FDG and 68 Ga-DOTATATE PET imaging between January 2020 and September 2022 were enrolled. Dual-tracer uptake patterns were classified into 3 groups: A. 68 Ga-DOTATATE positive and 18 F-FDG negative, B. 68 Ga-DOTATATE positive and 18 F-FDG positive, and C. 68 Ga-DOTATATE negative and 18 F-FDG positive. Descriptive statistics were used to evaluate the heterogeneity of dual-tracer uptake patterns among different grading (G) groups, between primary and metastatic lesions, and staging changes. Moreover, dual-tracer uptake patterns, grade, age, sex, and stage were compared with progression-free survival (PFS) by Cox regression., Results: In the different G groups, none of the patients with dual-tracer uptake pattern A had grade 3 histology, but 57% of patients with grade 1 disease had FDG avidity (25% of them resulting in dual-tracer uptake pattern C). Patients with no metastasis were well differentiated, but one of them presented with dual-tracer uptake pattern C. Different uptake patterns were also observed between primary and metastatic lesions, particularly 44% of patients with dual-tracer uptake pattern A of primary with FDG avidity of metastases. Moreover, 9 (17.6%) had new lesions detected by additional 18 F-FDG PET imaging, and 3 of them (5.9%) had clinical stage changed accordingly. The Cox regression test showed that the dual-tracer uptake patterns were significantly correlated with PFS by univariate and multivariate analyses ( P = 0.026 and 0.039, respectively), whereas the grade and stage did not correlate with survival (all P >0.05)., Conclusion: The current study has proven the uptake heterogeneity of the NET at initial diagnosis and demonstrated the staging and prognostic value of dual-tracer PET imaging. Our preliminary results have confirmed the importance of dual-tracer imaging modalities and concluded that dual-tracer PET imaging could be considered as prognostic tool for all patients with an initial diagnosis of NET., Competing Interests: Conflicts of interest and sources of funding: none declared. This study was supported by the National Natural Science Foundation of China (grant 81971653) and the “1.3.5” Project for Disciplines of Excellence, West China Hospital, Sichuan University (grant ZYJC21063)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A decreased autophagic capacity of bone marrow mesenchymal stromal cells (BMSCs) has been suggested to be an important cause of decreased osteogenic differentiation. A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate osteoporosis., Aim: To explore the effects of sinomenine (SIN) on the osteogenic differentiation of BMSCs and the underlying mechanisms., Methods: For in vitro experiments, BMSCs were extracted from sham-treated mice and ovariectomized mice, and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concentrations of SIN and the autophagy inhibitor 3-methyladenine. In vivo , the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse femur., Results: SIN reduced the levels of AKT and mammalian target of the rapamycin (mTOR) phosphorylation in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway, inhibited mTOR activity, and increased autophagy ability of BMSCs, thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in vivo ., Conclusion: The Chinese medicine SIN has potential for the treatment of various types of osteoporosis, bone homeostasis disorders, and autophagy-related diseases., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury (DILI) caused by different drugs and their correlation with clinical indicators., Method: The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests (RUCAM) scoring criteria and clinically diagnosed with DILI. Based on Chinese herbal medicine, cardiovascular drugs, non-steroidal anti-inflammatory drugs (NSAIDs), anti-infective drugs, and other drugs, patients were divided into five groups. Cytokines were measured by Luminex technology. Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed., Results: 73 patients were enrolled. Age among five groups was statistically different ( P = 0.032). Alanine aminotransferase (ALT) ( P = 0.033) and aspartate aminotransferase (AST) ( P = 0.007) in NSAIDs group were higher than those in chinese herbal medicine group. Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with Chinese herbal medicine (IL-6: P < 0.001; TNF-α: P < 0.001) and cardiovascular medicine (IL-6: P = 0.020; TNF-α: P = 0.001) were lower than those in NSAIDs group. There was a positive correlation between ALT ( r = 0.697, P = 0.025), AST ( r = 0.721, P = 0.019), and IL-6 in NSAIDs group., Conclusion: Older age may be more prone to DILI. Patients with NSAIDs have more severe liver damage in early stages of DILI, TNF-α and IL-6 may partake the inflammatory process of DILI., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Acetaminophen (APAP), the most frequently used mild analgesic and antipyretic drug worldwide, is implicated in causing 46% of all acute liver failures in the USA and between 40% and 70% in Europe. The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine (NAC); however, its efficacy is limited in cases of advanced liver injury or when administered at a late stage. In the current study, we discovered that treatment with a moderate intensity static magnetic field (SMF) notably reduced the mortality rate in mice subjected to high-dose APAP from 40% to 0%, proving effective at both the initial liver injury stage and the subsequent recovery stage. During the early phase of liver injury, SMF markedly reduced APAP-induced oxidative stress, free radicals, and liver damage, resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione (GSH). During the later stage of liver recovery, application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation. Moreover, the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery, even 24 h post overdose, when the effectiveness of NAC alone substantially declines. Overall, this study provides a non-invasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose. Of note, this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP, and potentially other toxic overdoses.

Food allergy (FA) poses a growing global food safety concern, yet no effective cure exists in clinics. Previously, we discovered a potent antifood allergy compound, butyrolactone I (BTL-I, 1 ), from the deep sea. Unfortunately, it has a very low exposure and poor pharmacokinetic (PK) profile in rats. Therefore, a series of structural optimizations toward the metabolic pathways of BTL-I were conducted to provide 18 derives ( 2 - 19 ). Among them, BTL-MK ( 19 ) showed superior antiallergic activity and favorable pharmacokinetics compared to BTL-I, being twice as potent with a clearance (CL) rate of only 0.5% that of BTL-I. By oral administration, C max and area under the concentration-time curve (AUC 0-∞ ) were 565 and 204 times higher than those of BTL-I, respectively. These findings suggest that butyrolactone methyl ketone (BTL-BK) could serve as a drug candidate for the treatment of FAs and offer valuable insights into optimizing the druggability of lead compounds.

Background: Cryoglobulinemia with pulmonary involvement is rare, and its characteristics, radiological findings, and outcomes are still poorly understood., Methods: Ten patients with pulmonary involvement of 491 cryoglobulinemia patients at Peking Union Medical College Hospital were enrolled in this retrospective study. We analyzed the characteristics, radiological features and management of pulmonary involvement patients, and compared with those of non-pulmonary involvement with cryoglobulinemia., Results: The 10 patients with pulmonary involvement (2 males; median age, 53 years) included three patients with type I cryoglobulinemia and seven patients with mixed cryoglobulinemia. All of 10 patients were IgM isotype cryoglobulinemia. All type I patients were secondary to B-cell non-Hodgkin lymphoma. Four mixed patients were essential, and the remaining patients were secondary to infections (n = 2) and systemic lupus erythematosus (n = 1), respectively. Six patients had additional affected organs, including skin (60%), kidney (50%), peripheral nerves (30%), joints (20%), and heart (20%). The pulmonary symptoms included dyspnea (50%), dry cough (30%), chest tightness (30%), and hemoptysis (10%). Chest computed tomography (CT) showed diffuse ground-glass opacity (80%), nodules (40%), pleural effusions (30%), and reticulation (20%). Two patients experienced life-threatening diffuse alveolar hemorrhage. Five patients received corticosteroid-based regimens, and four received rituximab-based regimens. All patients on rituximab-based regimens achieved clinical remission. The estimated two-year overall survival (OS) was 40%. Patients with pulmonary involvement had significantly worse OS and progression-free survival than non-pulmonary involvement patients of cryoglobulinemia (P < 0.0001)., Conclusions: A diagnosis of pulmonary involvement should be highly suspected for patients with cryoglobulinemia and chest CT-indicated infiltrates without other explanations. Patients with pulmonary involvement had a poor prognosis. Rituximab-based treatment may improve the outcome., (© 2024. The Author(s).)

The aim of study was to address the effects of manganese and iron, alone and in combination, on apoptosis of BV2 microglia cells, and to determine if combined exposure to these metals augments their individual toxicity. We used a murine microglial BV2 cell line. Cell cytotoxicity was analyzed by propidium iodide (PI) exclusion assay. Cell ROS production was analyzed by 2', 7'-dichlorofluorescin diacetate (DCFH-DA) probe staining. Pro-inflammatory cytokine production was monitored by ELISA. Cell apoptosis was analyzed by PE Annexin V/7-AAD staining. Mitochondrial membrane integrity was analyzed by flow cytometry. We used immunoblotting to analyze the effect of manganese, iron alone, or their combined exposure on the activation of caspase9, P53, Bax, and Bcl2 apoptosis signaling pathways. Caspase3 activity was determined using a Colorimetric. Manganese, iron, and their combined exposure for 24 h induced the activation of BV2 microglia cells and increased ROS production and the expression of the inflammatory cytokines, IL-1β and TNF-α. And we also found that the apoptosis rate increased, mitochondrial membrane potential decreased, apoptosis-related proteins caspase9, P53, Bax, and Bcl2 expression increased, and caspase3 activity increased. Furthermore, we found that combined manganese-iron cytotoxicity was lower than that induced by manganese exposure alone. Manganese, iron alone, or their combination exposure can induce apoptosis in glial cells. Iron can reduce the toxicity of manganese, and there is an antagonistic effect between manganese and iron., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Current methods for arene hydrogenation generally need either harsh reaction conditions or complex catalyst preparation. Here we describe a mild and convenient protocol that only utilizes commercially available catalysts. Using [Rh(nbd)Cl] 2 and Pd/C together as catalysts, arenes bearing various functional groups can be hydrogenated under 1 atm of H 2 at room temperature. This arene hydrogenation can also be achieved using catalysts of [Rh(cod)Cl] 2 and PtO 2 , thus avoiding glovebox manipulations and simplifying the reaction procedure.

Background: Abusive supervision by the nurse manager significantly influences nurses' withholding voice about patient safety. The role of impression management motivation and speak up-related climate is crucial in understanding their connection. This study aimed to explore the relationship between abusive supervision, impression management motivation, speak up-related climate, and withholding voice about patient safety., Methods: This cross-sectional study employed a convenience sampling method to recruit 419 clinical nurses from Taizhou Hospital, Zhejiang Province, China, between 1 November 2022 and 31 January 2023. The study adhered to the STROBE checklist. Abusive supervision and impression management motivation were assessed using the Chinese versions of the Abusive Supervision Scale and the Impression Management Motivation Scale, respectively. Withholding voice about patient safety and speak up-related climate were identified using the Chinese version of the Speaking Up about Patient Safety Questionnaire., Results: Nurse leaders' abusive supervision (β=0.40, p<0.01) and nurses' impression management motivation (β=0.10, p<0.01) significantly and positively influenced nurses' withholding voice about patient safety. We introduced impression management motivation as a mediating variable, and the effect of abusive supervision on nurses' withholding voice decreased (β from 0.40 to 0.38, p< 0.01). Nurses' speak up-related climate played a moderating role between abusive supervision and impression management motivation (β= 0.24, p<0.05)., Conclusions: Abusive supervision by nursing leaders can result in nurses withholding voice about patient safety out of self-protective impression management motives. This phenomenon inhibits nurses' subjective initiative and undermines their proactive involvement in improving patient safety, and hinders the cultivation of a culture encouraging full participation in patient safety, which should warrant significant attention., (© 2024. The Author(s).)

Remediating soil contaminated with polycyclic aromatic hydrocarbons (PAHs) presents a significant environmental challenge due to their toxic and carcinogenic properties. Traditional PAHs remediation methods-chemical, thermal, and bioremediation-along with conventional soil-washing agents like surfactants and cyclodextrins face challenges of cost, ecological harm, and inefficiency. Here we show an effective and environmentally friendly calixarene derivative for PAHs removal through soil washing. Thiacalix[4]arene tetrasulfonate (TCAS) has a unique molecular structure of a sulfonate group and a sulfur atom, which enhances its solubility and facilitates selective binding with PAHs. It forms host-guest complexes with PAHs through π-π stacking, OH-π interactions, hydrogen bonding, van der Waals forces, and electrostatic interactions. These interactions enable partial encapsulation of PAH molecules, aiding their desorption from the soil matrix. Our results show that a 0.7% solution of TCAS can extract approximately 50% of PAHs from contaminated soil while preserving soil nutrients and minimizing adverse environmental effects. This research unveils the pioneering application of TCAS in removing PAHs from contaminated soil, marking a transformative advancement in resource-efficient and sustainable soil remediation strategies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

To analyze the factors associated with the overall patient condition and explore the clinical value of the Patient Global Assessment (PGA) index for assessing the disease state in patients with Ankylosing Spondylitis (AS). This cross-sectional study used a standardized questionnaire to record the basic information of patients with AS. The collected data included the Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP), ASDAS-erythrocyte sedimentation rate (ESR), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), PGA, and other clinical indicators. Statistical analysis was performed using SPSS 25.0 software, and the scale was assessed for retest reliability and structural validity. The Kruskal-Wallis H test and Spearman or Pearson correlation analysis were used to analyze the factors influencing PGA scores. The receiver operator characteristic (ROC) curve was used to identify the cutoff value of the PGA for predicting disease activity in AS. The patient age, disease duration, family history, and history of ocular inflammation significantly differed between PGA groups (P < .05). The median PGA was significantly lower in patients with disease remission than in those with disease activity (P < .01). The various clinical indexes significantly differed between PGA groups (P < .01). The PGA was significantly correlated with various clinical indicators (P < .01). The area under the ROC curve (AUC) for disease activity based on the ASDAS-CRP was 0.743 (P < .01) with a PGA cutoff value of 1.38; the AUC for disease activity based on the BASDAI was 0.715 (P < .01) with a PGA cutoff value of 1.63. The PGA was significantly correlated with patient-reported outcomes, disease activity, function, and psychological status, and may indicate the level of inflammation in patients with AS. A PGA of around 1.5 indicates disease activity., Competing Interests: None of the authors has any conflicts of interest to declare., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Premature ovarian insufficiency (POI) is a major cause of infertility. In this study, we aimed to investigate the effects of the combination of bone marrow mesenchymal stem cells (BMSCs) and moxibustion (BMSCs-MOX) on POI and evaluate the underlying mechanisms., Methods: A POI rat model was established by injecting different doses of cyclophosphamide (Cy). The modeling of POI and the effects of the treatments were assessed by evaluating estrous cycle, serum hormone levels, ovarian weight, ovarian index, and ovarian histopathological analysis. The effects of moxibustion on BMSCs migration were evaluated by tracking DiR-labeled BMSCs and analyzing the expression of chemokines stromal cell-derived factor 1 (Sdf1) and chemokine receptor type 4 (Cxcr4). Mitochondrial function and mitophagy were assessed by measuring the levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATP, and the mitophagy markers (Drp1, Pink1, and Parkin). Furthermore, the mitophagy inhibitor Mdivi-1 and the mitophagy activator CCCP were used to confirm the role of mitophagy in Cy-induced ovarian injury and the underlying mechanism of combination therapy., Results: A suitable rat model of POI was established using Cy injection. Compared to moxibustion or BMSCs transplantation alone, BMSCs-MOX showed improved outcomes, such as reduced estrous cycle disorders, improved ovarian weight and index, normalized serum hormone levels, increased ovarian reserve, and reduced follicle atresia. Moxibustion enhanced Sdf1 and Cxcr4 expression, promoting BMSCs migration. BMSCs-MOX reduced ROS levels; upregulated MMP and ATP levels in ovarian granulosa cells (GCs); and downregulated Drp1, Pink1, and Parkin expression in ovarian tissues. Mdivi-1 significantly mitigated mitochondrial dysfunction in ovarian GCs and improved ovarian function. CCCP inhibited the ability of BMSCs-MOX treatment to regulate mitophagy and ameliorate Cy-induced ovarian injury., Conclusions: Moxibustion enhanced the migration and homing of BMSCs following transplantation and improves their ability to repair ovarian damage. The combination of BMSCs and moxibustion effectively reduced the excessive activation of mitophagy, which helped prevent mitochondrial damage, ultimately improving ovarian function. These findings provide a novel approach for the treatment of pathological ovarian aging and offer new insights into enhancing the efficacy of stem cell therapy for POI patients., (© 2024. The Author(s).)

Chinese wingnut ( Pterocarya stenoptera ) is a medicinally and economically important tree species within the family Juglandaceae. However, the lack of high-quality reference genome has hindered its in-depth research. In this study, we successfully assembled its chromosome-level genome and performed multi-omics analyses to address its evolutionary history and synthesis of medicinal components. A thorough examination of genomes has uncovered a significant expansion in the Lateral Organ Boundaries Domain gene family among the winged group in Juglandaceae. This notable increase may be attributed to their frequent exposure to flood-prone environments. After further differentiation between Chinese wingnut and Cyclocarya paliurus , significant positive selection occurred on the genes of NADH dehydrogenase related to mitochondrial aerobic respiration in Chinese wingnut, enhancing its ability to cope with waterlogging stress. Comparative genomic analysis revealed Chinese wingnut evolved more unique genes related to arginine synthesis, potentially endowing it with a higher capacity to purify nutrient-rich water bodies. Expansion of terpene synthase families enables the production of increased quantities of terpenoid volatiles, potentially serving as an evolved defense mechanism against herbivorous insects. Through combined transcriptomic and metabolomic analysis, we identified the candidate genes involved in the synthesis of terpenoid volatiles. Our study offers essential genetic resources for Chinese wingnut, unveiling its evolutionary history and identifying key genes linked to the production of terpenoid volatiles., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Background: Hepatocellular carcinoma (HCC) patients complicated with portal vein tumor thrombus (PVTT) exhibit poor prognoses and treatment responses., Aim: To investigate efficacies and safety of the combination of PD-1 inhibitor, transcatheter arterial chemoembolization (TACE) and Lenvatinib in HCC subjects comorbid with PVTT., Methods: From January 2019 to December 2020, HCC patients with PVTT types I-IV were retrospectively enrolled at Beijing Ditan Hospital. They were distributed to either the PTL or TACE/Lenvatinib (TL) group. The median progression-free survival (mPFS) was set as the primary endpoint, while parameters like median overall survival, objective response rate, disease control rate (DCR), and toxicity level served as secondary endpoints., Results: Forty-one eligible patients were finally recruited for this study and divided into the PTL ( n = 18) and TL ( n = 23) groups. For a median follow-up of 21.8 months, the DCRs were 88.9% and 60.9% in the PTL and TL groups ( P = 0.046), res-pectively. Moreover, mPFS indicated significant improvement (HR = 0.25; P < 0.001) in PTL-treated patients (5.4 months) compared to TL-treated (2.7 months) patients. There were no treatment-related deaths or differences in adverse events in either group., Conclusion: A triplet regimen of PTL was safe and well-tolerated as well as exhibited favorable efficacy over the TL regimen for advanced-stage HCC patients with PVTT types I-IV., Competing Interests: Conflict-of-interest statement: All authors certify that there is no conflict of interest related to the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Layered transition metal oxides (Na x TMO 2 ) possess attractive features such as large specific capacity, high ionic conductivity, and a scalable synthesis process, making them a promising cathode candidate for sodium-ion batteries (SIBs). However, Na x TMO 2 suffer from multiple phase transitions and Na + /vacancy ordering upon Na + insertion/extraction, which is detrimental to their electrochemical performance. Herein, we developed a novel cathode material that exhibits an abnormal P2-type structure at a stoichiometric content of Na up to 1. The cathode material delivers a reversible capacity of 108 mA h g -1 at 0.2C and 97 mA h g -1 at 2C, retaining a capacity retention of 76.15% after 200 cycles within 2.0-4.3 V. In situ diffraction studies demonstrated that this material exhibits an absolute solid-solution reaction with a low volume change of 0.8% during cycling. This near-zero-strain characteristic enables a highly stabilized crystal structure for Na + storage, contributing to a significant improvement in battery performance. Overall, this work presents a simple yet effective approach to realizing high Na content in P2-type layered oxides, offering new opportunities for high-performance SIB cathode materials., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Macrophages are phenotypically and functionally diverse in the tumor microenvironment (TME). However, how to remodel macrophages with a protumor phenotype and how to manipulate them for therapeutic purposes remain to be explored. Here, we show that in the TME, RARγ is downregulated in macrophages, and its expression correlates with poor prognosis in patients with colorectal cancer (CRC). In macrophages, RARγ interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6), which prevents TRAF6 oligomerization and autoubiquitination, leading to inhibition of nuclear factor κB signaling. However, tumor-derived lactate fuels H3K18 lactylation to prohibit RARγ gene transcription in macrophages, consequently enhancing interleukin-6 (IL-6) levels in the TME and endowing macrophages with tumor-promoting functions via activation of signal transducer and activator of transcription 3 (STAT3) signaling in CRC cells. We identified that nordihydroguaiaretic acid (NDGA) exerts effective antitumor action by directly binding to RARγ to inhibit TRAF6-IL-6-STAT3 signaling. This study unravels lactate-driven macrophage function remodeling by inhibition of RARγ expression and highlights NDGA as a candidate compound for treating CRC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Postzygotic reproductive isolation, which results in the irreversible divergence of species, is commonly accompanied by hybrid sterility, necrosis/weakness, or lethality in the F 1 or other offspring generations. Here we show that the loss of function of HWS1 and HWS2, a couple of duplicated paralogs, together confer complete interspecific incompatibility between Asian and African rice. Both of these non-Mendelian determinants encode the putative Esa1-associated factor 6 (EAF6) protein, which functions as a characteristic subunit of the histone H4 acetyltransferase complex regulating transcriptional activation via genome-wide histone modification. The proliferating tapetum and inappropriate polar nuclei arrangement cause defective pollen and seeds in F 2 hybrid offspring due to the recombinant HWS1/2-mediated misregulation of vitamin (biotin and thiamine) metabolism and lipid synthesis. Evolutionary analysis of HWS1/2 suggests that this gene pair has undergone incomplete lineage sorting (ILS) and multiple gene duplication events during speciation. Our findings have not only uncovered a pair of speciation genes that control hybrid breakdown but also illustrate a passive mechanism that could be scaled up and used in the guidance and optimization of hybrid breeding applications for distant hybridization., (© 2024. The Author(s).)

It remains a tremendous challenge to achieve high-efficiency bifunctional electrocatalysts for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) for hydrogen production by water splitting. Herein, a novel hybrid of 0D nickel nanoparticles dispersed on the one-dimensional (1D) molybdenum carbide micropillars embedded in the carbon layers (Ni/Mo 2 C@C) was successfully prepared on nickel foam by a facile pyrolysis strategy. During the synthesis process, the nickel nanoparticles and molybdenum carbide were simultaneously generated under H 2 and C 2 H 2 mixed atmospheres and conformally encapsulated in the carbon layers. Benefiting from the distinctive 0D/1D heterostructure and the synergistic effect of the biphasic Mo 2 C and Ni together with the protective effect of the carbon layer, the reduced activation energy barriers and fast catalytic reaction kinetics can be achieved, resulting in a small overpotential of 96 mV for the HER and 266 mV for the OER at the current density of 10 mA cm -2 together with excellent durability in 1.0 M KOH electrolyte. In addition, using the developed Ni/Mo 2 C@C as both the cathode and anode, the constructed electrolyzer exhibits a small voltage of 1.55 V for the overall water splitting. The novel designed Ni/Mo 2 C@C may give inspiration for the development of efficient bifunctional catalysts with low-cost transition metal elements for water splitting.