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This review summarizes the progress in the research on polyoxometalate (POM)-decorated gold (Au) and silver (Ag) core-shell structures (Au/Ag@POMs), emphasizing their substantial application potential in catalysis, medicine, and biology. It outlines the central strategies for fabricating Au/Ag@POMs with diverse morphologies and dimensions, leveraging POMs as protective ligands and reducing agents as well as for ligand exchange. Of particular note is the focus on the analysis of the nanoparticle size, shape, and intricate architecture of POM shells using cryo-electron microscopy techniques. By integrating recent findings on atomically precise POM-stabilized nanoclusters, this review delves deeper into understanding surface interface structures, intrinsic atomic architectures, and electronic interactions between POM shells and metallic cores. Collectively, advancements in this field underscore significant strides in the controllable synthesis and precise structural manipulation of Au/Ag@POM architectures, thus paving the way for engineering high-performance metal catalysts.

Primary malignant melanoma of the esophagus (PMME) is an extremely rare esophageal malignancy that is often misdiagnosed or overlooked due to its atypical symptoms. We report a case of a 75-year-old male patient who presented with progressive dysphagia. Endoscopic examination revealed a black mass located 25 cm from the incisors. Further imaging studies, including computed tomography (CT) and emission computed tomography (ECT), showed significant thickening of the mid-esophageal wall with localized soft tissue mass formation and heterogeneous enhancement on contrast scans. Multiple lymph nodes around the lesion were visible, leading to an initial misdiagnosis of esophageal cancer. Additionally, metabolic abnormalities in the left scapula suggested possible bone metastasis of the tumor. The final pathological diagnosis was esophageal melanoma. After thorough evaluation of the patient's medical history and additional relevant tests, the primary origin was considered. Diagnosing primary malignant melanoma of the esophagus is a challenging task. This case, through the combination of endoscopic examination, imaging, and pathology, illustrates the characteristics of PMME, providing important insights for clinicians and emphasizing the necessity of comprehensive early evaluation to improve diagnostic accuracy and treatment outcomes., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

This study aims to investigate the effects of Linggui Zhugan Decoction(LGZGD) on myocardial fibrosis(MF) and the Lats1/Yap signaling pathway in mice after myocardial infarction(MI), exploring its role and mechanism in inhibiting MF. The MI-induced ischemic mouse model was established by left anterior descending coronary artery ligation, followed by continuous intervention for six weeks. Doppler ultrasound imaging-system of small animals was used to detect left ventricular ejection fraction(LVEF), left ventricular fractional shortening(LVFS), left ventricular internal diameter at end-systole(LVIDs), and left ventricular internal diameter at end-diastole(LVIDd). Pathological changes in myocardial tissue were observed by HE and Masson staining. Serum levels of creatine kinase isoenzyme MB(CK-MB) and lactate dehydrogenase(LDH) were detected by using ELISA. Myocardial tissue mRNA levels of Lats1, Yap, and connective tissue growth factor(CTGF) were determined by RT-qPCR. Protein expression of alpha-smooth muscle actin(α-SMA), collagen Ⅰ(Col Ⅰ), collagen Ⅲ(Col Ⅲ), tissue inhibitor of metal protease 1(TIMP1), matrix metallopeptidase 2(MMP2), Yap, p-Yap, and n-Yap was determined by Western blot. Compared with the sham group, the model group showed significantly decreased LVEF and LVFS levels, increased LVIDd and LVIDs levels(P<0.01), disordered arrangement of myocardial cells, partial fracture of myocardial fibers, and massive deposition of collagen fibers. Moreover, serum levels of CK-MB and LDH were significantly increased(P<0.01), while myocardial tissue mRNA levels of Lats1 were significantly decreased(P<0.01), and mRNA levels of Yap and CTGF were significantly increased(P<0.01). Protein expression of α-SMA, Col Ⅰ, Col Ⅲ, MMP2, Yap, and n-Yap was significantly increased(P<0.01), while protein expression of Lats1, TIMP1, p-Yap, and the ratio of p-Yap/Yap were significantly decreased(P<0.01). Compared with the model group, after intervention with LGZGD(9.36 g·kg~(-1)), mice showed significantly increased LVEF and LVFS levels, decreased LVIDd and LVIDs levels(P<0.01), more orderly arrangement of myocardial cells, significantly reduced myocardial fiber fracture and collagen fiber deposition. Serum levels of CK-MB and LDH were significantly decreased(P<0.01), while myocardial tissue mRNA levels of Lats1 were significantly increased(P<0.01), and mRNA levels of Yap and CTGF were significantly decreased(P<0.01). Protein expression of α-SMA, Col Ⅰ, Col Ⅲ, MMP2, Yap, and n-Yap was significantly decreased(P<0.01), while protein expression of Lats1, TIMP1, p-Yap, and the ratio of p-Yap/Yap were significantly increased(P<0.01). LGZGD can inhibit MF in mice after MI and improve mouse cardiac function, which is closely related to the activation of the Lats1/Yap signaling pathway.

Atherosclerotic cardiovascular disease is closely correlated with elevated low density lipoprotein-cholesterol. In feeding state, glucose and insulin activate mammalian target of rapamycin 1 that phosphorylates the deubiquitylase ubiquitin-specific peptidase 20 (USP20). USP20 then stabilizes HMG-CoA reductase, thereby increasing lipid biosynthesis. In this study, we applied clinically approved lipid nanoparticles to encapsulate the siRNA targeting Usp20. We demonstrated that silencing of hepatic Usp20 by siRNA decreased body weight, improved insulin sensitivity, and increased energy expenditure through elevating UCP1. In Ldlr -/- mice, silencing Usp20 by siRNA decreased lipid levels and prevented atherosclerosis. This study suggests that the RNAi-based therapy targeting hepatic Usp20 has a translational potential to treat metabolic disease., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Hypoxia can aggravate tumor occurrence, development, invasion, and metastasis, and greatly inhibit the photodynamic therapy (PDT) effect. Herein, carbon nitride (CNs)-based DNA and photosensitizer co-delivery systems (BPSCNs) with oxygen-producing functions are developed to address this problem. Selenide glucose (Seglu) is used as the dopant to prepare red/NIR-active CNs (SegluCNs). The tumor-targeting unit Bio-PEG 2000 is utilized to construct BPSCNs nanoparticles through esterification reactions. Furthermore, DNA hydrophobization is realized via mixing P53 gene with a positively charged mitochondrial-targeted near-infrared (NIR) emitting photosensitizer (MTTPY), which is encapsulated in non-cationic BPSCNs for synergistic delivery. Ester bonds in BPSCNs@MTTPY-P53 complexes can be disrupted by lipase in the liver to facilitate P53 release, upregulated P53 expression, and promoted HIF-1α degradation in mitochondria. In addition, the oxygen produced by the complexes improved the hypoxic microenvironment of hepatocellular carcinoma (HCC), synergistically downregulated HIF-1α expression in mitochondria, promoted mitochondrial-derived ferroptosis and enhanced the PDT effect of the MTTPY unit. Both in vivo and in vitro experiments indicated that the transfected P53-DNA, produced O 2 and ROS by these complexes synergistically led to mitochondrial-derived ferroptosis in hepatoma cells through the HIF-1α/SLC7A11 pathway, and completely avoiding PDT resistance caused by hypoxia, exerting a significant therapeutic role in HCC treatment., (© 2024 Wiley‐VCH GmbH.)

The development of stable fluorescent sensors for toxic pollutants and drugs is meaningful to the environment and public health. In this work, nitrogen-doped graphene quantum dots (N-GQDs) were facially synthesized by a one-step hydrothermal method using soluble starch and l-arginine as carbon and nitrogen sources in pure water at 190 °C for 4 h. The as-synthesized N-GQDs were well characterized and displayed blue fluorescence emission at 445 nm with excellent pH stability, salt tolerance, thermostability, photobleaching resistance and reproducibility. Moreover, N-GQDs could serve as an "on-off" sensor for selective detection of Cr(vi) and folic acid with low detection limit (0.80 and 2.1 μM), good linear correlation over wide linear range (0-50 μM and 0-200 μM) as well as short response time (<10 s). The practical applications of N-GQDs for Cr(vi) and folic acid detection in actual samples were further investigated and showed acceptable recoveries (92-105%) with relative standard deviations less than 5%. These results indicated that this N-GQDs-based sensor could be a potential alternative for Cr(vi) and folic acid detection in the fields of environmental monitoring and drug analysis., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Chronic stress-induced neuroinflammation plays a pivotal role in the development and exacerbation of mental disorders, such as anxiety and depression. Dimethyl Fumarate (DMF), an effective therapeutic agent approved for the treatment of multiple sclerosis, has been widely reported to display anti-inflammatory and anti-oxidative effects. However, the impact of DMF on chronic stress-induced anxiety disorders and the exact underlying mechanisms remain largely unknown., Methods: We established a mouse model of chronic social defeat stress (CSDS). DMF was administered orally 1 h before daily stress session for 10 days in CSDS + DMF group. qRT-PCR and western blotting were used to analyze mRNA and protein expression of NLRP3, Caspase-1 and IL-1β. Immunofluorescence staining was carried out to detect the expression of Iba 1 and c-fos positive cells as well as morphological change of Iba 1 + microglia. Whole-cell patch-clamp recording was applied to evaluate synaptic transmission and intrinsic excitability of neurons., Results: DMF treatment significantly alleviated CSDS-induced anxiety-like behaviors in mice. Mechanistically, DMF treatment prevented CSDS-induced neuroinflammation by inhibiting the activation of microglia and NLRP3/Caspase-1/IL-1β signaling pathway in basolateral amygdala (BLA), a brain region important for emotional processing. Furthermore, DMF treatment effectively reversed the CSDS-caused disruption of excitatory and inhibitory synaptic transmission balance, as well as the increased intrinsic excitability of BLA neurons., Conclusions: Our findings provide new evidence that DMF may exert anxiolytic effect by preventing CSDS-induced activation of NLRP3/Caspase-1/IL-1β signaling pathway and alleviating hyperactivity of BLA neurons., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rosemary is one of the most promising, versatile, and studied natural preservatives. Carnosic acid (CA) and carnosol (CARN), as the primary active ingredients of rosemary extracts, have little difference in structure, but their antioxidant activities vary significantly, depending on the system studied. The underlying molecular mechanisms remain unclear. By means of optical spectroscopies, stopped-flow, laser photolysis, and density functional theory (DFT) calculations, we have compared CA and CARN between their reaction dynamics of radical scavenging, metal ion chelation, and oxidation inhibition in lipid emulsion and beef, as well as between their interactions with β-carotene (β-Car). For reference, 3-isopropyl catechol (IC), which is structurally similar to the active groups of CA and CARN, was studied in parallel. It is found for CA that the intramolecular hydrogen bond can boost the acidity of its phenol hydroxyl and that the synergistic effect with β-Car can substantially enhance its antioxidation activity in the model systems of lipid and meat via the CA-to-β-Car electron transfer reaction. The substitution of A and B rings on the catechol group in both CA and CARN limits browning caused by their formation of oxidative products as antioxidants.

Purpose: Our study aimed to develop and validate a homologous recombination deficiency (HRD) scoring algorithm in the Chinese breast cancer population., Methods and Materials: Ninety-six in-house breast cancer (BC) samples and 6 HRD-positive standard cells were analyzed by whole-genome sequencing (WGS). Besides, 122 BCs from the TCGA database were down-sampled to ~ 1X WGS. We constructed an algorithm named AcornHRD for HRD score calculated based on WGS at low coverage as input data to estimate large-scale copy number alteration (LCNA) events on the genome. A clinical cohort of 50 BCs (15 cases carrying BRCA mutation) was used to assess the association between HRD status and anthracyclines-based neoadjuvant treatment outcomes., Results: A 100-kb window was defined as the optimal size using 41 in-house cases and the TCGA dataset. HRD score high threshold was determined as HRD score ≥ 10 using 55 in-house BCs with BRCA mutation to achieve a 95% BRCA-positive agreement rate. Furthermore, the HRD status agreement rate of AcornHRD is 100%, while the ShallowHRD is 60% in standard cells. BRCA mutation was significantly associated with a high HRD score evaluated by AcornHRD and ShallowHRD (p = 0.008 and p = 0.003, respectively) in the TCGA dataset. However, AcornHRD showed a higher positive agreement rate than did the ShallowHRD algorithm (70% vs 60%). In addition, the BRCA-positive agreement rate of AcornHRD was superior to that of ShallowHRD (87% vs 13%) in the clinical cohort. Importantly, the high HRD score assessed by AcornHRD was significantly correlated with a residual cancer burden score of 0 or 1 (RCB0/1). Besides, the HRD-positive group was more likely to respond to anthracycline-based chemotherapy than the HRD-negative group (pCR [OR = 9.5, 95% CI 1.11-81.5, p = 0.040] and RCB0/1 [OR = 10.29, 95% CI 2.02-52.36, p = 0.005])., Conclusion: Using the AcornHRD algorithm evaluation, our analysis demonstrated the high performance of the LCNA genomic signature for HRD detection in breast cancers., (© 2024. The Author(s).)

Hypoxia can lead to liver fibrosis and severely limits the efficacy of photodynamic therapy (PDT). Herein, carbon nitride (CN)-based hybrid nanoparticles (NPs) VPSGCNs@TSI for light-driven water splitting were utilized to solve this problem. CNs were doped with selenide glucose (Se-glu) to enhance their red/NIR region absorption. Then, vitamin A-poly(ethylene glycol) (VA-PEG) fragments and aggregation-induced emission (AIE) photosensitizers TSI were introduced into Se-glu-doped CN NPs (VPSGCNs) to construct VPSGCNs@TSI NPs. The introduction of VA-PEG fragments enhanced the targeting of the NPs to activated hepatic stellate cells (HSCs) and reduced their toxicity to ordinary liver cells. VPSGCN units could trigger water splitting to generate O 2 under 660 nm laser irradiation, improve the hypoxic environment of the fibrosis site, downregulate HIF-1α expression, and activate HSC ferroptosis via the HIF-1α/SLC7A11 pathway. In addition, generated O 2 could also increase the reactive oxygen species (ROS) production of TSI units in a hypoxic environment, thereby completely reversing hypoxia-triggered PDT resistance to enhance the PDT effect. The combination of water-splitting materials and photodynamic materials showed a 1 + 1 > 2 effect in increasing oxygen levels in liver fibrosis, promoting ferroptosis of activated HSCs and reversing PDT resistance caused by hypoxia.

Sterol-regulatory element binding proteins (SREBPs) are a conserved transcription factor family governing lipid metabolism. When cellular cholesterol level is low, SREBP2 is transported from the endoplasmic reticulum to the Golgi apparatus where it undergoes proteolytic activation to generate a soluble N-terminal fragment, which drives the expression of lipid biosynthetic genes. Malfunctional SREBP activation is associated with various metabolic abnormalities. In this study, we find that overexpression of the active nuclear form SREBP2 (nSREBP2) causes caspase-dependent lytic cell death in various types of cells. These cells display typical pyroptotic and necrotic signatures, including plasma membrane ballooning and release of cellular contents. However, this phenotype is independent of the gasdermin family proteins or mixed lineage kinase domain-like (MLKL). Transcriptomic analysis identifies that nSREBP2 induces expression of p73, which further activates caspases. Through whole-genome CRISPR-Cas9 screening, we find that Pannexin-1 (PANX1) acts downstream of caspases to promote membrane rupture. Caspase-3 or 7 cleaves PANX1 at the C-terminal tail and increases permeability. Inhibition of the pore-forming activity of PANX1 alleviates lytic cell death. PANX1 can mediate gasdermins and MLKL-independent cell lysis during TNF-induced or chemotherapeutic reagents (doxorubicin or cisplatin)-induced cell death. Together, this study uncovers a noncanonical function of SREBPs as a potentiator of programmed cell death and suggests that PANX1 can directly promote lytic cell death independent of gasdermins and MLKL., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The concentration of immunoglobulin (Ig) E is the lowest among serum Igs, but it can induces type I hypersensitivity and plays an important role in anti-parasitic infection. The present study aimed to explore the residence characteristics of IgE + cells in the sheep small intestine and the impact of Moniezia benedeni infection on them. The recombinant plasmids pET-28a-IgE were constructed and induced and expressed in Escherichia coli. BL21 (DE3). The rabbit anti-sheep IgE polyclonal antibody was prepared using the obtained recombinant protein as antigen. Finally, the levels of IgE + cells in the small intestine of healthy (Control group) and naturally M. benedeni-infected (Infected group) sheep were detected analyzed. The results showed that the rabbit anti-sheep IgE polyclonal antibody with good immunogenicity (titer = 1: 128000) could specifically bind to the heavy chain of natural sheep IgE. In the Control group, the IgE + cells were mainly distributed in lamina propria of the small intestine, and the densities were significantly decreased from duodenum to ileum (P<0.05), with respective values of (4.28 cells / 10 4 μm 2 , 1.80 cells / 10 4 μm 2 , and 1.44 cells / 10 4 μm 2 in duodenum, jejunum, and ileum. In the Infected group, IgE + cells density were 6.26 cells / 10 4 μm 2 , 3.01 cells / 10 4 μm 2 , and 2.09 cells / 10 4 μm 2 in duodenum, jejunum and ileum respectively, which were significantly higher in all segments compared to the Control group (P<0.05), increasing by 46.26%, 67.22% and 45.14%, respectively. In addition, compared with the Control group, the IgE protein levels were significantly increased in all intestinal segments of the Infected group (P<0.01), however, there was no significant differences among the different intestinal segments within the same group (P>0.05). The results demonstrated that M. benedeni infection could significantly increase the content of IgE and the distribution density of its secreting cells in sheep small intestine. The intestinal mucosal immune system of sheep presented obvious specificity against M. benedeni infection. This lays a good foundation for further exploring molecular mechanisms of the intestinal mucosal immune system monitoring and responding to M. benedeni infection., 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.)

Bisphenol A (BPA) is a common component in the manufacture of daily plastic consumer goods. Recent studies have suggested that prenatal exposure to BPA can increase the susceptibility of offspring to mental illness, although the underlying mechanisms remain unclear. In this study, we performed transcriptomic and epigenomic profiling in the adult mouse brain following prenatal exposure to low-dose BPA. We observed a sex-specific transcriptional dysregulation in the cortex, with more significant differentially expressed genes was observed in adult cortex from male offspring. Moreover, the upregulated genes primarily influenced neuronal functions, while the downregulated genes were significantly associated with energy metabolism pathways. More evidence supporting impaired mitochondrial function included a decreased ATP level and a reduced number of mitochondria in the cortical neuron of the BPA group. We further investigated the higher-order chromatin regulatory patterns of DEGs by incorporating published Hi-C data. Interestingly, we found that upregulated genes exhibited more distal interactions with multiple enhancers, while downregulated genes displayed relatively short-range interactions among adjacent genes. Our data further revealed decreased H3K9me3 signal on the distal enhancers of upregulated genes, whereas increased DNA methylation and H3K27me3 signals on the promoters of downregulated genes. In summary, our study provides compelling evidence for the potential health risks associated with prenatal exposure to BPA, and uncovers sex-specific transcriptional changes with a complex interplay of multiple epigenetic mechanisms., (© 2024. The Author(s).)

Fe(II) regeneration is decisive for highly efficient H 2 O 2 -based Fenton-like processes, but the role of cobalt-containing reactive sites in promoting Fe(II) regeneration was overlooked. Herein, a single atom Co-N-C catalyst was employed in Fe(II)/H 2 O 2 system to promote the degradation of diverse organic contaminants. The EPR and quenching experiments indicated Co-N-C significantly enhanced the generation of superoxide species, and accelerated hydroxyl radical generation for pollutant degradation. The electrochemical and surface composition analyses demonstrated the enhanced H 2 O 2 activation and Fe(III)/Fe(II) recycling on the catalyst. Furthermore, in-situ Raman characterization with shell-isolated gold nanoparticles was employed to visualize the interfacial reactive intermediates and their time-resolved interaction. The accumulation of interfacial CoOOH* was confirmed when Co-N-C activated H 2 O 2 alone, but it rapidly transformed into FeOOH* upon Fe(II) addition. Besides, the temporal variation of OOH* intermediates and the relative intensity of Co(III)-O and Co(IV)=O peaks depicted the dynamic interaction of reactive intermediates along the H 2 O 2 consumption. With this basis, we proposed a mechanism of interfacial OOH* mediated Fe(II) regeneration, which overcame the kinetical limitation of Fe(II)/H 2 O 2 system. Therefore, this study provided a primary effort to elucidate the overlooked role of interfacial CoOOH* in the Fenton-like processes, which may inspire the design of more efficient catalysts., 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: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC., Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821., Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group., Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile., Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project., Competing Interests: We declare no competing interests., (© 2024 Published by Elsevier Ltd.)

Alzheimer's disease (AD) is a neurodegenerative disease that seriously threatens the quality of life of the elderly. Its pathogenesis has not yet been fully elucidated. Ferroptosis, a cell death caused by excessive accumulation of iron-dependent lipid peroxides, has been implicated in the pathogenesis of AD. Uncontrolled lipid peroxidation is the core process of ferroptosis, and inhibiting lipid peroxidation of ferroptosis may be an important therapeutic target for AD. Based on previous studies, we mixed standards of icariin, astragaloside IV, and puerarin, named the standard mixture YHG, and investigated the effect of YHG on ferroptosis -lipid peroxidation in APP/PS1 mice. DFX, a ferroptosis inhibitor, was used as a control drug. In this study, APP/PS1 mice were used as an AD animal model, and behavioral experiments, iron level detection, Transmission electron microscopy (TEM) observation, lipid peroxidation level detection, antioxidant capacity detection, immunofluorescence, Western blot and real-time qPCR were performed. It was found that YHG could reduce body weight, significantly improve abnormal behaviors and the ultrastructure of hippocampal neurons in APP/PS1 mice. The results of biochemical tests showed that YHG reduced the contents of iron, malondialdehyde (MDA) and lipid peroxide (LPO) in brain tissue and serum, and increased the levels of superoxide dismutase (SOD) and reduced glutathione (GSH). Immunofluorescence, WesternBlot and real-time qPCR results showed that YHG could promote the expression of solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member 2 (SLC3A2) and glutathione peroxidase 4(GPX4). Inhibited the expression of long-chain acyllipid coenzyme a synthetase 4(ACSL4) and lysophosphatidyltransferase 3 (LPCAT3). This study suggests that the mechanism by which YHG improves cognitive dysfunction in APP/PS1 mice may be related to the inhibition of ferroptosis-lipid peroxidation., 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 Ltd. All rights reserved.)

A new lignan, named pouzolignan P ( 1 ), together with 14 known ones ( 2 - 15 ) were isolated from the roots of Pouzolzia zeylanica (L.) Benn. Their structures were deduced based on the detailed spectroscopic analysis. All the isolates were evaluated for their inhibitory activities toward the ATP citrate lyase (ACLY). Among them, four lignans, isopouzolignan K ( 3 ), gnemontanins E ( 5 ), gnetuhainin I ( 6 ), and styraxlignolide D ( 15 ) showed excellent ACLY inhibitory effect with IC 50 values of 9.06, 0.59, 2.63, and 7.62 μM, respectively. These compounds were further evaluated for their cholesterol-lowing effects on ox-LDL-induced high-cholesterol HepG2 cells. Compound 15 emerges as the most potent ACLY inhibitor, which significantly decreased the TC level in a dose-dependent manner. In addition, molecular docking simulations elucidated that 15 formed a strong hydrogen-bond interaction with Glu599 of ACLY, which was an important site responsible for the enzyme catalytic activity.

In recent years, advancements in single-cell and spatial transcriptomics, which are highly regarded developments in the current era, particularly the emerging integration of single-cell and spatiotemporal transcriptomics, have enabled a detailed molecular comprehension of the complex regulation of cell fate. The insights obtained from these methodologies are anticipated to significantly contribute to the development of personalized medicine. Currently, single-cell technology is less frequently utilized for prostate cancer compared with other types of tumors. Starting from the perspective of RNA sequencing technology, this review outlined the significance of single-cell RNA sequencing (scRNA-seq) in prostate cancer research, encompassing preclinical medicine and clinical applications. We summarize the differences between mouse and human prostate cancer as revealed by scRNA-seq studies, as well as a combination of multi-omics methods involving scRNA-seq to highlight the key molecular targets for the diagnosis, treatment, and drug resistance characteristics of prostate cancer. These studies are expected to provide novel insights for the development of immunotherapy and other innovative treatment strategies for castration-resistant prostate cancer. Furthermore, we explore the potential clinical applications stemming from other single-cell technologies in this review, paving the way for future research in precision medicine., (© 2024. The Author(s).)

Human-specific insertions play important roles in human phenotypes and diseases. Here we reported a 446-bp insertion (Insert-446) in intron 11 of the TBC1D8B gene, located on chromosome X, and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome 5. Interestingly, Insert-446 was present in the human Neanderthal and Denisovans genomes, and was fixed in humans after human-chimpanzee divergence. We have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in macaques. In addition, over-expression TBC1D8B promoted cell proliferation and migration through "a dual finger" catalytic mechanism (Arg538 and Gln573) in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in vivo. Knockout of Insert-446 prevented cell proliferation and migration in cancer and normal cells. Our results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B gene. These findings provide a significant insight into the effects of human-specific insertions on evolution., (© 2023. Science China Press.)

To solve the problems of the lack of property research in organic synthesis experiments and the relative independence of instrumental analytical methods in experiments, we designed a comprehensive undergraduate experiment based on mechanofluorochromic materials. In this project, 4-[bis(4-methylphenyl)amino] benzaldehyde was synthesized via the Vilsmeier-Haack reaction using 4,4'-dimethyltriphenylamine as the raw material. The product was then characterized by mass spectrometry, infrared absorption spectroscopy, and nuclear magnetic resonance spectroscopy. The solvatofluorochromism and mechanofluorochromism of the target material were studied using ultraviolet-visible absorption spectroscopy, fluorescence spectroscopy, etc. Furthermore, the mechanism of mechanofluorochromism was determined using powder X-ray diffraction. Organic synthesis and a series of instrumental analytical methods were combined to form an integrated experiment. The experiment is interesting, scientific, and comprehensive for undergraduates as a creative exercise; moreover, it can inspire their interest in chemical research, cultivate a variety of experimental operation abilities, improve creative-thinking skills, and encourage the development of effective solutions to existing problems in chemical experiments.

Objective: This study aimed to translate and culturally adapt the standardized outcomes in nephrology-hemodialysis fatigue (SONG-HD fatigue) scale and to assess the psychometric properties of the Chinese version of the SONG-HD fatigue (C-SONG-HD fatigue) scale., Methods: Forward and back translations were used to translate the SONG-HD fatigue scale into Chinese. We used the C-SONG-HD fatigue scale to survey Chinese patients undergoing hemodialysis (HD) in China. We examined the distribution of responses and floor and ceiling effects. Cronbach's alpha and McDonald's omega coefficient, intraclass coefficients, and Spearman correlations were used to assess internal consistency reliability, test-retest reliability, and convergent validity, respectively. Responsiveness was also evaluated., Results: In total, 489 participants across southeast China, northwest China, and central China completed the study. The C-SONG-HD fatigue scale had good internal consistency (Cronbach's alpha coefficient 0.861, omega coefficient 0.916), test-retest reliability (intraclass correlation coefficient 0.695), and convergent validity (Spearman correlation 0.691). The analysis of all first-time HD patients did not show notable responsiveness, and only patients with temporary vascular access had good responsiveness with an effect size (ES) of 0.54, a standardized response mean (SRM) of 0.85, and a standard error of measurement (SEM) of 0.77., Conclusion: The Chinese version of the SONG-HD fatigue scale showed satisfactory reliability and validity in patients undergoing hemodialysis (HD) in China. It could be used as a tool to measure the fatigue of Chinese HD patients., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Blood vessels constitute a closed pipe system distributed throughout the body, transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys. Changes in blood vessels are related to many disorders like stroke, myocardial infarction, aneurysm, and diabetes, which are important causes of death worldwide. Translational research for new approaches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems. Although mice or rats have been widely used, applying data from animal studies to human-specific vascular physiology and pathology is difficult. The rise of induced pluripotent stem cells (iPSCs) provides a reliable in vitro resource for disease modeling, regenerative medicine, and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells. This review summarizes the latest progress from the establishment of iPSCs, the strategies for differentiating iPSCs into vascular cells, and the in vivo transplantation of these vascular derivatives. It also introduces the application of these technologies in disease modeling, drug screening, and regenerative medicine. Additionally, the application of high-tech tools, such as omics analysis and high-throughput sequencing, in this field is reviewed., 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.)

Mitochondria are dynamically changing organelles that maintain stable mitochondrial morphology, number, and function through constant fusion and division, a process known as mitochondrial dynamics, which is an important mechanism for mitochondrial quality control. Excessive fusion and division of mitochondria can lead to a homeostatic imbalance in mitochondrial dynamics, causing mitochondrial dysfunction, leading to cellular damage, and even death. The physiological functions of the kidney are mainly powered by mitochondria, and homeostatic imbalance in mitochondrial dynamics affects mitochondrial function and is closely related to renal diseases such as acute kidney injury and diabetic nephropathy. This article reviews the regulation of mitochondrial kinetics, how imbalances in mitochondrial kinetic homeostasis affect mitochondrial injury, and the impact of mitochondrial injury on renal pathophysiology, in order to improve understanding and knowledge of the role of mitochondria in renal disease.

Introduction: Continuous cropping affected the stability of soil enzyme activity and the structural characteristics of microbial community. Owing to challenges in the study of complex rhizosphere microbial communities, the composition and function of these microbial communities in farmland ecosystems remain elusive. Here, we studied the microbial communities of the rhizosphere of wine grapes with different years of continuous cropping and investigated their relationships with soil enzyme activity., Methods: Metagenomic sequencing was conducted on the rhizosphere soils from one uncultivated wasteland and four vineyards with varying durations of continuous cropping., Results: The predominant microbial were bacteria (98.39%), followed by archaea (1.15%) and eukaryotes (0.45%). Continuous cropping caused a significant increase in the relative abundance of Rhizobiales and Micrococcales but a marked decrease in Solirubrobacterales . At the genus level, 75, 88, 65, 132, and 128 microbial genera were unique to uncultivated wasteland, 5, 10, 15, and 20 years of continuous cropping, respectively. The relative abundance of genes with signal transduction function was the highest. The activity of all enzymes measured in this study peaked at 5 years of continuous cropping, and then decreased with 10 to 15 year of continuous cropping, but increased at 20 years again. In addition, soil enzyme activity, especially of alkaline phosphatase was significantly correlated with the diversity of the dominant microorganisms at the genus level. Moreover, the coupled enzyme activities had a greater impact on the diversity of the microbial community than that of individual enzymes., Conclusion: Our findings reveal the composition and function of the soil microbial communities and enzymes activity in response to changes in cropping years, which has important implications for overcoming continuous cropping obstacles and optimizing land use., 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 Song, Zhu, Li and Wang.)

Defect engineering is promising to tailor the physical properties of 2D semiconductors for function-oriented electronics and optoelectronics. Compared with the extensively studied 2D binary materials, the origin of defects and their influence on physical properties of 2D ternary semiconductors are not clarified. Here, the effect of defects on the electronic structure and optical properties of few-layer hexagonal Znln 2 S 4 is thoroughly studied via versatile spectroscopic tools in combination with theoretical calculations. It is demonstrated that the Zn-In antistructural defects induce the formation of a series of donor and acceptor energy levels and sulfur vacancies induce donor energy levels, leading to rich recombination paths for defect emission and extrinsic absorption. Impressively, the emission of donor-acceptor pair in Znln 2 S 4 can be significantly tailored by electrostatic gating due to efficient tunability of Fermi level (E f ). Furthermore, the layer-dependent dipole orientation of defect emission in Znln 2 S 4 is directly revealed by back focal plane imagining, where it presents obviously in-plane dipole orientation within a dozen-layer thickness of Znln 2 S 4 . These unique features of defects in Znln 2 S 4 including extrinsic absorption, rich recombination paths, gate tunability, and in-plane dipole orientation are definitely a benefit to the advanced orientation-functional optoelectronic applications., (© 2023 Wiley-VCH GmbH.)

Interleukin-1β (IL-1β)-induced signaling is one of the most important pathways in regulating inflammation and immunity. The assembly of the receptor complex, consisting of the ligand IL-1β, the IL-1 receptor (IL-1R) type 1 (IL1R1), and the IL-1R accessory protein (IL1RAP), initiates this signaling. However, how the IL1R1-associated complex is regulated remains elusive. Angiopoietin like 3 (ANGPTL3), a key inhibitor of plasma triglyceride clearance, is mainly expressed in the liver and exists in both intracellular and extracellular secreted forms. Currently, ANGPTL3 has emerged as a highly promising drug target for hypertriglyceridemia and associated cardiovascular diseases. However, most studies have focused on the secreted form of ANGPTL3, while its intracellular role is still largely unknown. Here, we report that intracellular ANGPTL3 acts as a negative regulator of IL-1β-triggered signaling. Overexpression of ANGPTL3 inhibited IL-1β-induced NF-κB activation and the transcription of inflammatory genes in HepG2, THP1, and HEK293T cells, while knockdown or knockout of ANGPTL3 resulted in opposite effects. Mechanistically, ANGPTL3 interacted with IL1R1 and IL1RAP through its intracellular C-terminal fibrinogen-like domain and disrupted the assembly of the IL1R1-associated complex. Taken together, our study reveals a novel role for ANGPTL3 in inflammation, whereby it inhibits the physiological interaction between IL1R1 and IL1RAP to maintain immune tolerance and homeostasis in the liver., (© The Author(s) (2023). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)

Objectives: To evaluate the efficacy and safety of biliary stenting implantation with iodine-125 seed strand (SI) followed by hepatic artery infusion chemotherapy (HAIC) plus lenvatinib (Len) with programmed death-1 (PD-1) inhibitor for patients diagnosed with extrahepatic cholangiocarcinoma (ECC) and malignant obstructive jaundice (MOJ)., Methods: In this single-center retrospective study, the data of ECC patients with MOJ from March 2015 to January 2023 was assessed. Using probability score matching (PSM), the selection bias of patients was reduced. Primary study outcomes included overall survival (OS) and progression-free survival (PFS). The OS and PFS were performed using the Kaplan-Meier method and evaluated with the log-rank test., Results: A total of 104 patients were enrolled finally, including 52 patients treated with interventional therapy (SI+HAIC) plus Len with PD-1 inhibitor (SI+HAIC+Len+P group) and 52 patients treated with interventional therapy (SI+HAIC) plus lenvatinib (SI+HAIC+Len group). 26 pairs of patients were matched after PSM analysis. After PSM analysis, the median OS and PFS in the SI+HAIC+Len+P group were significantly longer compared to those in the SI+HAIC+Len group (OS:16.6 vs. 12.3 months, P = 0.001; PFS:12.6 vs 8.5 months, P = 0.004). The DCR was significantly different between groups ( P = 0.039), while ORR not ( P = 0.548). The addition of PD-1 inhibitor was generally well tolerated without treatment-associated mortality., Conclusion: Interventional therapy (SI+HAIC) plus Len with PD-1 inhibitor was effective for ECC patients accompanied by MOJ with a manageable safety profile., 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 Lin, Ke, Chen, Yang, Huang and Wu.)

Background: Some studies have shown that gut microbiota may be associated with dementia. However, the causal effects between gut microbiota and different types of dementia and whether cytokines act as a mediator remain unclear., Methods: Gut microbiota, cytokines, and five dementia types, including Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy body (DLB), vascular dementia (VD), and Parkinson's disease dementia (PDD) were identified from large-scale genome-wide association studies (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships between gut microbiota, cytokines, and five types of dementia. Inverse variance weighting (IVW) was used as the main statistical method. In addition, we explored whether cytokines act as a mediating factor in the pathway from gut microbiota to dementia., Results: There were 20 positive and 16 negative causal effects between genetic liability in the gut microbiota and dementia. Also, there were five positive and four negative causal effects between cytokines and dementias. Cytokines did not act as mediating factors., Conclusions: Gut microbiota and cytokines were causally associated with five types of dementia, and cytokines seemed not to be the mediating factors in the pathway from gut microbiota to dementia., (© 2023. The Author(s).)

Objectives: This study aimed to investigate the efficacy and safety of transarterial chemoembolization (TACE) plus camrelizumab, a monoclonal antibody targeting programmed death-1, and apatinib for patients with intermediate and advanced hepatocellular carcinoma (HCC) in a real-world setting., Methods: A total of 586 HCC patients treated with either TACE plus camrelizumab and apatinib (combination group, n = 107) or TACE monotherapy (monotherapy group, n = 479) were included retrospectively. Propensity score matching analysis was used to match patients. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety in the combination group were described in comparison to monotherapy., Results: After propensity score matching (1:2), 84 patients in the combination group were matched to 147 patients in the monotherapy group. The median age was 57 years and 71/84 (84.5%) patients were male in the combination group, while the median age was 57 years with 127/147 (86.4%) male in the monotherapy group. The median OS, PFS, and ORR in the combination group were significantly higher than those in the monotherapy group (median OS, 24.1 vs. 15.7 months, p = 0.008; median PFS, 13.5 vs. 7.7 months, p = 0.003; ORR, 59.5% [50/84] vs. 37.4% [55/147], p = 0.002). On multivariable Cox regression, combination therapy was associated with significantly better OS (adjusted hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.26-0.64; p < 0.001) and PFS (adjusted HR, 0.52; 95% CI, 0.37-0.74; p < 0.001). Grade 3 or 4 adverse events occurred in 14/84 (16.7%) and 12/147 (8.2%) in the combination and monotherapy groups, respectively., Conclusions: TACE plus camrelizumab and apatinib showed significantly better OS, PFS, and ORR versus TACE monotherapy for predominantly advanced HCC., Clinical Relevance Statement: Compared with TACE monotherapy, TACE plus immunotherapy and molecular targeted therapy showed better clinical efficacy for predominantly advanced HCC patients, with a higher incidence of adverse events., Key Points: • This propensity score-matched study demonstrates that TACE plus immunotherapy and molecular targeted therapy have a longer OS, PFS, and ORR compared with TACE monotherapy in HCC. • Grade 3 or 4 adverse events occurred in 14/84 (16.7%) patients treated with TACE plus immunotherapy and molecular targeted therapy compared with 12/147 (8.2%) patients in the monotherapy group, while no grade 5 adverse events were observed in all cohorts., (© 2023. The Author(s).)

Ectothermic fish exposure to hypothermal stress requires adjusting their metabolic molecular machinery, which was investigated using Indian medaka ( Oryzias dancena ; 10 weeks old, 2.5 ± 0.5 cm) cultured in fresh water (FW) and seawater (SW; 35‱) at room temperature (28 ± 1 °C). The fish were fed twice a day, once in the morning and once in the evening, and the photoperiod was 12 h:12 h light: dark. In this study, we applied two hypothermal treatments to reveal the mechanisms of energy metabolism via pgc-1α regulation in the gills of Indian medaka; cold-stress (18 °C) and cold-tolerance (extreme cold; 15 °C). The branchial ATP content was significantly higher in the cold-stress group, but not in the cold-tolerance group. In FW- and SW-acclimated medaka, the expression of genes related to mitochondrial energy metabolism, including pgc-1α , prc , Nrf2 , tfam , and nd5, was analyzed to illustrate differential responses of mitochondrial energy metabolism to cold-stress and cold-tolerance environments. When exposed to cold-stress, the relative mRNA expression of pgc-1α , prc , and Nrf2 increased from 2 h, whereas that of tfam and nd5 increased significantly from 168 h. When exposed to a cold-tolerant environment, prc was significantly upregulated at 2 h post-cooling in the FW and SW groups, and pgc-1α was significantly upregulated at 2 and 12 h post-cooling in the FW group, while tfam and nd5 were downregulated in both FW and SW fish. Hierarchical clustering revealed gene interactions in the cold-stress group, which promoted diverse mitochondrial energy adaptations, causing an increase in ATP production. However, the cold-tolerant group demonstrated limitations in enhancing ATP levels through mitochondrial regulation via the PGC-1α energy metabolism pathway. These findings suggest that ectothermic fish may develop varying degrees of thermal tolerance over time in response to climate change. This study provides insights into the complex ways in which fish adjust their metabolism when exposed to cold stress, contributing to our knowledge of how they adapt.

The application of biochar can improve soil fertility and benefit sustainable agricultural development and carbon neutrality simultaneously. To better understand the effects of biochar addition on nitrogen transformation and N 2 O emission in a coastal saline-alkali soil and its potential mechanisms, we conducted a 60-day laboratory incubation experiment with six treatments, i.e ., ammonium sulfate (N 150 mg·kg -1 ), ammonium sulfate + 0.4% (weight/weight) biochar, ammonium sulfate + 0.6% biochar, ammonium sulfate + 0.8% biochar, ammonium sulfate + 1.6% biochar, and ammonium sulfate + 0.2% biochar and 0.2% organic fertilizer (based on equivalent N basis). The results showed that soil nitrogen transformation was mainly affected by biochar addition at the early stage of incubation. Biochar addition significantly increased the contents of nitrate and ammonium. Biochar addition significantly increased soil net nitrification rate, but the magnitude of such increases decreased with increasing biochar addition level. Similar temporal change patterns of N 2 O emissions were observed in all treatments, and the N 2 O emissions mainly occurred in the first 30 days of incubation. Compared with the CK, biochar addition significantly reduced the cumulative N 2 O emission, and the decrement increased with increasing biochar addition levels. In conclusion, the effects of biochar and nitrogen fertilizer addition on soil nitrogen transformation and N 2 O emission varied with the application rate. Biochar addition with a rate of 0.8% (W/W) increased soil inorganic nitrogen content and decreased soil N 2 O emission. It could provide theoretical basis and reference for the formulation of reasonable plans for the improvement and utilization of biochar in coastal saline-alkali soil.

Background: Therapy for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) is still controversial. This study was performed to evaluate the efficacy and safety of the combination therapy comprising transarterial chemoembolization (TACE), lenvatinib (L), programmed death-1 inhibitor (P), and iodine-125 seed (I 125 ) brachytherapy relative to TACE in combination with lenvatinib plus programmed death-1 inhibitor therapy and TACE plus lenvatinib therapy., Methods: The data of HCC patients with PVTT from July 2017 to August 2022 were assessed in this single-center retrospective study. Primary study outcomes were progression-free survival (PFS) and overall survival (OS), while the secondary outcomes were disease control rate (DCR), objective response rate (ORR), and treatment-related adverse events., Results: We enrolled 150 patients totally, including 50 patients treated with TACE plus lenvatinib therapy (TACE+L group), 45 patients treated with TACE in combination with lenvatinib plus programmed death-1 inhibitor therapy (TACE+L+P group), and 55 patients treated with the combination therapy of TACE along with I 125 brachytherapy, lenvatinib, and programmed death-1 inhibitor therapy (TACE+L+P+I 125 group). The median OS in the TACE+L+P+I 125 group (21.0; 95% confidence interval [CI]: 18.4∼23.5 months) was significantly longer than that in the TACE+L group (10; 95% CI: 7.8∼12.1months) (p = 0.006), while it was insignificantly longer than that in the TACE+L+P group (14.0; 95% CI: 10.7∼17.2months) (p = 0.058). The median PFS in the TACE+L+P+I 125 group (13.0; 95% CI: 10.2∼15.7 months) was significantly longer than that in the TACE+L group (5.0; 95% CI: 4.2∼5.7 months) (p = 0.014) and the TACE+L+P group (9.0; 95% CI: 6.7∼11.2 months) (p = 0.048). Statistically significant differences between groups were found in DCR (p = 0.015). There were no significant between-group differences in treatment-related adverse events (p > 0.05)., Conclusions: A combination therapy of TACE, lenvatinib, programmed death-1 inhibitor, and I 125 seed brachytherapy significantly improve OS, PFS, and DCR and show better survival prognosis for HCC patients accompanied by PVTT., (Copyright © 2023 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

In this work, a 2-(2'-hydroxyphenyl)benzimidazole derived fluorescent probe, 2-(2'-hydroxy-4'-aminophenyl)benzimidazole (4-AHBI), was synthesized and its fluorescent behavior toward triphosgene were evaluated. The results showed that 4-AHBI exhibited high sensitivity (limit of detection, 0.08 nM) and excellent selectivity for triphosgene over other acyl chlorides including phosgene in CH 2 Cl 2 solution. Moreover, 4-AHBI loaded test strips were prepared for the practical sensing of triphosgene., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

CdE (E = S, Se) quantum dots (QDs) with a broad and large Stokes shift PL emission have emerged as potential materials for white-light LEDs. However, this surface-related emission of nanocrystals is currently limited by low quantum efficiency. Herein, a convenient noninjected one-pot method at a relatively low temperature to prepare CdS QDs was readily achieved. The CdS-368 QD displays intense broad yellow emission in both solution and the solid state at room temperature. The coligation of organic and inorganic ligands passivates the electron trap states at the QD surface and suppresses nonradiative recombination, which is responsible for the high stability of colloids in organic solvents and the distinct fluorescence quantum yield.

Objective: This study aimed to noninvasively characterize the metabolic alterations in ischemic brain tissues using Z-spectrum-fitted multiparametric chemical exchange saturation transfer-weighted magnetic resonance imaging (CEST-MRI)., Methods: Three sets of Z-spectrum data with saturation power (B 1 ) values of 1.5, 2.5, and 3.5 µT, respectively, were acquired from 17 patients with ischemic stroke. Multiple contrasts contributing to the Z-spectrum, including fitted amide proton transfer (APT fitted ), +2 ppm peak (CEST@2ppm), concomitantly fitted APT fitted and CEST@2ppm (APT&CEST@2ppm), semisolid magnetization transfer contrast (MT), aliphatic nuclear Overhauser effect (NOE), and direct saturation of water (DSW), were fitted with 4 and 5 Lorentzian functions, respectively. The CEST metrics were compared between ischemic lesions and contralateral normal white matter (CNWM), and the correlation between the CEST metrics and the apparent diffusion coefficient (ADC) was assessed. The differences in the Z-spectrum metrics under varied B 1 values were also investigated., Results: Ischemic lesions showed increased APT fitted , CEST@2ppm, APT&CEST@2ppm, NOE, and DSW as well as decreased MT. APT&CEST@2ppm, MT, and DSW showed a significant correlation with ADC [APT&CEST@2ppm at the 3 B 1 values: R=0.584/0.467/0.551; MT at the 3 B 1 values: R=-0.717/-0.695/-0.762 (4-parameter fitting), R=-0.734/-0.711/-0.785 (5-parameter fitting); DSW of 4-/5-parameter fitting: R=0.794/0.811 (2.5 µT), R=0.800/0.790 (3.5 µT)]. However, the asymmetric analysis of amide proton transfer (APT asym ) could not differentiate the lesions from CNWM and showed no correlation with ADC. Furthermore, the Z-spectrum contrasts varied with B 1 ., Conclusion: The Z-spectrum-fitted multiparametric CEST-MRI can comprehensively detect metabolic alterations in ischemic brain tissues., (© 2023. Huazhong University of Science and Technology.)

In this paper, we report the successful assembly of achiral {Ln 6 M} ([Ln 6 M(μ 3 -OH) 8 (acac) 12 (CH 3 O) x (CH 3 OH) y ], Ln = La, M = Mn, Co, Fe) and chiral {Nd 9 Fe 2 } ([Nd 9 Fe 2 (μ 4 -O)(μ 3 -OH) 14 (acac) 16 (NO 3 )(CH 3 OH) 2 (H 2 O) 3 ]) rare earth clusters using achiral rigid ligands and a transition metal doping strategy. {Ln 6 M} can be viewed as the fusion of two {Ln 3 M} tetrahedrons by sharing vertices. {Nd 9 Fe 2 } results from the fusion of four {Ln 3 M} tetrahedrons by vertice and edge sharing. The substitution of Ln with transition metal leads to changes in the coordination pattern around neighboring Ln, which triggers the switch of metal center chirality. This study demonstrates the potentiality of utilizing transition metal doping and rigid ligand to control the chirality of rare earth clusters. In addition, the photocatalytic CO 2 activity of these transition metal-doped rare earth clusters has been studied.

Atomic layer deposited Al 2 O 3 films are incorporated into miniature light emitting diodes (mini-LEDs) as an internal moisture barrier layer. The experimental results show that the water vapor transmission rate reaches ≤10 -4  g/m 2 /day when the Al 2 O 3 thickness is ≥40 nm. The mini-LED with a 40 nm-thick Al 2 O 3 layer shows negligible degradation after 1000 h of 85°C/85% relative humidity testing, whereas the device without an Al 2 O 3 layer fails after only 500 h due to delamination occurring at the GaN surface. Current-voltage characteristics of the device without an Al 2 O 3 moisture barrier layer indicate an increase in series resistance and ideality factor. This study provides a simple, light-weighting method to have a satisfactory encapsulation function for miniature LEDs.

Chromophoric dissolved organic matter (CDOM) plays an important role in ultraviolet (UV) light absorption in the ocean. CDOM is known to originate from either an allochthonous or autochthonous source and has varying compositions and levels of reactivity; however, the effects of individual radiation treatments and the combined effects of UVA and UVB on allochthonous and autochthonous CDOM remain poorly understood. Thus, here, we measured changes in the common optical properties of CDOM collected from China's marginal seas and the Northwest Pacific, using full-spectrum, UVA (315-400 nm), and UVB (280-315 nm) irradiation to induce photodegradation over the same time period (60 h). Excitation-emission matrices (EEMs) combined with parallel factor analysis (PARAFAC) identified four components: marine humic-like C1, terrestrial humic-like C2, soil fulvic-like C3, and tryptophan-like C4. Although the behaviours of these components during full-spectrum irradiation exhibited similar decreasing tendencies, three components (C1, C3, and C4) underwent direct photodegradation under UVB exposure, whereas C2 was more susceptible to UVA degradation. The diverse photoreactivities of the source-dependent components to different light treatments led to differing photochemical behaviours of other optical indices [a CDOM (355), a CDOM (254), S R , HIX, and BIX]. The results indicate that irradiation preferentially reduced the high humification degree or humic substance content of allochthonous DOM, and promoted the transformation from the allochthonous humic DOM components to recently produced components. Although values for the samples from different sources overlapped frequently, principal component analysis (PCA) indicated that the overall optical signatures could be linked to the original CDOM source features. The degradation of CDOM humification, aromaticity, molecular weight, and autochthonous fractions under exposure can drive the CDOM biogeochemical cycle in marine environments. These findings can aid in a better understanding of the effects of different combinations of light treatments and CDOM characteristics on CDOM photochemical processes., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: Food protein-induced enterocolitis syndrome (FPIES) is a delayed, non-IgE-mediated food allergy. This syndrome was once thought to be rare, but emerging literature suggests an increasing incidence along with more foods being implicated. Also, with the introduction of guidelines on early peanut introduction, peanut-induced FPIES seems to be increasing in Australia and USA. Although most patients are diagnosed with FPIES within the first year of life, most commonly with food triggers to cow's milk or soy, other phenotypes exist in comparison to this classic presentation. In this case report, we present a patient with late onset of acute FPIES at age 3 to walnut., Case Presentation: We describe a case of FPIES in a 12-year-old boy who had recurrent episodes of repetitive emesis, that began at age 3, each time after consuming walnuts. Mom does not give a history of intentional feeding (or avoidance) of walnut and/ or pecans. She also described possible reactions with pine nuts and macadamia. He was assessed with an oral food challenge to walnut, which triggered an episode of acute FPIES. He developed vomiting with onset 2 h post-ingestion, pallor, lethargy, and required an emergency department visit for anti-emetic medications and oral rehydration therapy. He improved on the therapy and now avoids cashew, pistachio, hazelnuts, walnuts, pecans, pine nuts, and macadamia nuts., Conclusions: This case report adds to the limited literature that exists on culprit food allergens in FPIES. We present an acute FPIES triggered by the ingestion of walnuts. The diagnosis, common food triggers, and natural history of FPIES are described. There remains a lack of information on the natural history of FPIES, especially towards uncommon food triggers and on FPIES that present beyond infancy., (© 2023. The Author(s).)

In this study, the phytohormone gibberellins (GAs) were used to enhance sulfamethoxazole (SMX) removal and lipid accumulation in the microalgae Chlorella vulgaris. At the concentration of 50 mg/L GAs, the SMX removal achieved by C. vulgaris was 91.8 % while the lipid productivity of microalga was at 11.05 mg/L d -1 , which were much higher than that without GAs (3.5 % for SMX removal and 0.52 mg/L d -1 for lipid productivity). Supplementation of GAs enhanced the expression of antioxidase-related genes in C. vulgaris as a direct response towards the toxicity of SMX. In addition, GAs increased lipid production of C. vulgaris by up-regulating the expression of genes related to carbon cycle of microalgal cells. In summary, exogenous GAs promoted the stress tolerance and lipid accumulation of microalgae at the same time, which is conducive to improving the economic benefits of microalgae-based antibiotics removal as well as biofuel production potential., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: The transforming growth factor β (TGFβ) signaling pathway plays a crucial role in the development of liver fibrosis by activating TGFβ type II receptor (TGFβR2), followed by the recruitment of TGFβR1 finally triggering downstream signaling pathway., Aim: To find drugs targeting TGFβR2 that inhibit TGFβR1/TGFβR2 complex formation, theoretically inhibit TGFβ signaling pathway, and thereby ameliorate liver fibrosis., Methods: Food and Drug Administration-approved drugs were screened for binding affinity with TGFβR2 by virtual molecular docking. We identified 6 candidates and further explored their potential by Cell Counting Kit-8 (CCK-8) cell cytotoxic experiment to validate toxicity and titrated the best cellular working concentrations. Next, we further demonstrated the detailed molecular working mechanisms using mutagenesis analysis. Finally, we used a mouse model to investigate its potential anti-liver fibrosis effect., Results: We identified 6 drug candidates. Among these 6 drugs, dihydroergotamine (DHE) shows great ability in reducing fibrotic gene expressions such as collagen, p-SMAD3, and α-SMA in TGFβ induced cellular model of liver fibrosis in LX-2 cells. Furthermore, we demonstrated that DHE binds to TGFβR2. Moreover, mutation of Leu27, Phe30, Thr51, Ser52, Ile53, and Glu55 of TGFβR2 disrupted the binding of TGFβR2 with DHE. In addition, DHE significantly improved liver fibrosis, as evidenced by Masson's trichrome staining of liver sections. This is further supported by the width and the velocity of the portal vein, and serum markers of liver function. In line with those observations, DHE also decreased macrophages infiltration and extracellular matrix deposition in the liver., Conclusion: DHE alleviates liver fibrosis by binding to TGFβR2 thereby suppressing TGFβ signaling pathway. We show here that as far as drug repurposing, DHE has great potential to treat liver fibrosis., Competing Interests: Conflict-of-interest statement: Dr. Xie reports in addition, Dr. Xie has a patent Application of dihydroergotamine in the treatment of liver fibrosis issued., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Chronic stress exposure increases the risk of mental health problems such as anxiety and depression. The medial prefrontal cortex (mPFC) is a hub for controlling stress responses through communicating with multiple limbic structures, including the basolateral amygdala (BLA) and nucleus accumbens (NAc). However, considering the complex topographical organization of the mPFC neurons in different subregions (dmPFC vs. vmPFC) and across multiple layers (Layer II/III vs. Layer V), the exact effects of chronic stress on these distinct mPFC output neurons remain largely unknown., Results: We first characterized the topographical organization of mPFC neurons projecting to BLA and NAc. Then, by using a typical mouse model of chronic restraint stress (CRS), we investigated the effects of chronic stress on the synaptic activity and intrinsic properties of the two mPFC neuronal populations. Our results showed that there was limited collateralization of the BLA- and NAc-projecting pyramidal neurons, regardless of the subregion or layer they were situated in. CRS significantly reduced the inhibitory synaptic transmission onto the BLA-projecting neurons in dmPFC layer V without any effect on the excitatory synaptic transmission, thus leading to a shift of the excitation-inhibition (E-I) balance toward excitation. However, CRS did not affect the E-I balance in NAc-projecting neurons in any subregions or layers of mPFC. Moreover, CRS also preferentially increased the intrinsic excitability of the BLA-projecting neurons in dmPFC layer V. By contrast, it even caused a decreasing tendency in the excitability of NAc-projecting neurons in vmPFC layer II/III., Conclusion: Our findings indicate that chronic stress exposure preferentially modulates the activity of the mPFC-BLA circuit in a subregion (dmPFC) and laminar (layer V) -dependent manner., (© 2023. The Author(s).)

Objective: To analyze the relationship between initial (within 24 hours) postoperative hemoglobin (Hb) value and prognosis in non-cardiac surgery patients receiving intraoperative blood transfusion, and to provide support for sensible blood use in surgery., Methods: A retrospective analysis was performed on all patients aged 18 or older who underwent non-cardiac surgeries and who received intraoperative blood transfusion at West China Hospital, Sichuan University from 2012 to 2018. According to their initial postoperative Hb levels, the patients were divided into 6 groups, including Hb<75 g/L, 75 g/L≤Hb<85 g/L, 85 g/L≤Hb<95 g/L, 95 g/L≤Hb<105 g/L, 105 g/L≤Hb<115 g/L, and Hb≥115 g/L goups. Multivariate linear regression was performed to examine the differences in the length-of-stay between the groups and binary logistic regression analysis was conducted to examine the differences between the groups in inpatient mortality, the rate of patient voluntary discharge against medical advice, incidence of acute ischemic injury, including acute kidney injury, myocardial infarction, and cerebral infarction, and length-of-stay longer than 28 days. In addition, the effects of multiple interactions between initial postoperative Hb and the types of surgery, the amount of intraoperative red blood cell infusion (red blood cell<8 U vs. red blood cell≥8 U), and preoperative anemia status (Hb<100 g/L vs. Hb≥100 g/L) on postoperative length-of-stay were analyzed., Results: A total of 7528 patients were included in this study. Compared to those of the reference group, the 95 g/L≤Hb<105 g/L group, the length-of-stay of patients with initial postoperative Hb<75 g/L increased and the mortality (odds ratio [ OR ]=2.562) and the rate of voluntary discharge against medical advice ( OR =1.681) increased significantly. Patients in the 75 g/L≤Hb<85 g/L group had increased length-of-stay and increased incidence of acute ischemic injury ( OR =1.778) relative to the reference group. The interaction analysis showed that there was significant interaction between initial postoperative Hb and the types of surgery, which influenced the postoperative length-of-stay., Conclusion: In non-cardiac surgery patients who have receive blood transfusion, initial postoperative Hb<85 g/L is associated with poorer prognosis. However, those patients with higher initial postoperative Hb did not gain more benefits, suggesting that 85 g/L≤Hb<95 g/L may be the target Hb value for sensible intraoperative transfusion., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

BACKGROUND We aimed to investigate the clinical efficacy of continuous renal replacement therapy (CRRT) in combination with peritoneal lavage for the treatment of severe acute pancreatitis. MATERIAL AND METHODS We retrospectively reviewed data from 52 patients with severe acute pancreatitis between January 2014 and December 2021 at Jiangyin People's Hospital. The patients were divided into 2 groups: CRRT (n=26) and CRRT in combination with peritoneal lavage (n=26). The following results and outcomes were retrospectively compared: procalcitonin, interleukin-6, and C-reactive protein levels, duration of systemic inflammatory response, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, abdominal distention relief time, abdominal pain relief time, length of intensive care unit stay, length of hospital stay, inpatient hospital costs, incidence of complications, and mortality. RESULTS There were significant differences in interleukin-6 and procalcitonin levels and APACHE-II scores after 3 and 7 days of treatment. The duration of systemic inflammatory response, abdominal distention relief time, abdominal pain relief time, length of intensive care unit stay, and length of hospital stay were considerably shorter in the combination group than in the CRRT group (P<0.01). Inpatient hospital costs were significantly lower in the combination group than in the CRRT group (P<0.01). However, incidence of complications and mortality showed no significant differences between the 2 groups. CONCLUSIONS CRRT combined with peritoneal lavage is an important adjuvant therapy in the early stages of acute severe acute pancreatitis and has better clinical efficacy than CRRT alone.