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Shi-Hua Yan,1,2 Yong Chen,3 Zhi-Qian Huang,1 Wen-Xi Zhong,1 Xiao-Tian Wang,1 Yang-Can Tang,1 Xu-Yi Zhao,1 Yu-Shan Wu,1 Chun Zhou,4 Wei Zhu,5 Wei Xiao,1,6 Xuan Li,2 Dong-Shu Zhang1,2 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 2Department of Traditional Chinese Medicine, The Tenth affiliated Hospital, Southern Medical University (Dongguan People’s Hospital), Dongguan, Guangdong, 523058, People’s Republic of China; 3Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 4School of Pharmaceutical Sciences; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 5Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, People’s Republic of China; 6Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of ChinaCorrespondence: Dong-Shu Zhang, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China, Email nyzds@sina.com Wei Xiao, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of China, Email xw7688@smu.edu.cnPurpose: Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown.Methods: This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10+, IFN-γ+ and FoxP3+CD4+T cells in murine spleen.Results: It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3+, IL-10+ and IFN-γ+ CD4+T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation.Conclusion: These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.Keywords: autologous whole blood, acupoint injection, atopic dermatitis, anti-idiotypic immunomodulation, Tregs

Xiao-Min Zhang, Ming-Hui Lun, Wei Du, Fang Ma, Ze-Qing Huang Department of Anesthesiology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institution, NO.44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning Province, 110042, People’s Republic of ChinaCorrespondence: Xiao-Min Zhang; Ze-Qing Huang Department of Anesthesiology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institution, No.44 Xiaoheyan Road, Dadong District, Shenyang, Liaoning Province, 110042, People’s Republic of China Email zhangxiaomin.99@163.com; huangzeqing0@163.comObjective: To observe the ameliorative effect of kappa opioid receptor (KOR) agonist on rats with neuropathic pain (NP) and investigate the mechanism of action of the calcium ion (Ca2+)/calcium/calmodulin-dependent protein kinase II (CaMKII)/cyclic AMP response element-binding protein (CREB) pathway.Methods: A total of 40 Sprague Dawley rats were randomly divided into four groups: sham-operation group (Sham group), NP model group (NP group), NP + KOR agonist U50488H group (NU group) and NP + specific CaMKII antagonist (KN93) + U50488H group (NKU group). The thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) of each group of rats were determined. ELISA was applied to examine the changes in inflammatory factors and oxidative stress factors, and the apoptotic rate in dorsal root ganglia was observed using TUNEL staining. Ca2+ concentration, content of oxidative stress index ROS and the release of calcitonin gene-related peptide (CGRP) and N-methyl-D-aspartate receptor (NMDAR) in the dorsal root ganglia were measured by the immunofluorescence assay. Finally, Western blotting was performed to detect expression changes in the Ca2+/CaMKII/CREB pathway.Results: The KOR agonist U50488H could improve the values of TWL and MWT of NP the rats, inhibit inflammatory responses and relieve oxidative stress injury. Its mechanisms of action were associated with U50488H repression of Ca2+ influx, reduction of CGRP and NMDAR releases in the dorsal root ganglia and decreases in CaMKII and CREB phosphorylations in NP rats.Conclusion: The KOR agonist ameliorates NP through suppressing the activity of the Ca2+/CaMKII/CREB pathway.Keywords: KORs, neuropathic pain, Ca2+, CaMKII, CREB

Yong-Pan Huang,1,* Fen-Fei Gao,1,* Bin Wang,1 Fu-Chun Zheng,2 Yan-Mei Zhang,1 Yi-Cun Chen,1 Zhan-Qin Huang,1 Yan-Shan Zheng,1 Shu-Ping Zhong,3 Gang-Gang Shi1,4 1Department of Pharmacology, 2Department of Pharmacy, First Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, People's Republic of China; 3Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, USA; 4Department of Cardiovascular Diseases, First Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, People's Republic of China *These authors contributed equally to this work Abstract: N-n-butyl haloperidol iodide (F2), a novel compound, has shown palliative effects in myocardial ischemia/reperfusion (I/R) injury. In this study, we investigated the effects of F2 on the extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)/Na+/H+ exchanger (NHE)/Na+/Ca2+ exchanger (NCX) signal-transduction pathway involved in H2O2-induced Ca2+ overload, in order to probe the underlying molecular mechanism by which F2 antagonizes myocardial I/R injury. Acute exposure of rat cardiac myocytes to 100 µM H2O2 increased both NHE and NCX activities, as well as levels of phosphorylated MEK and ERK. The H2O2-induced increase in NCX current (INCX) was nearly completely inhibited by the MEK inhibitor U0126 (1,4-diamino-2,3-dicyano-1,4-bis[o-aminophenylmercapto]butadiene), but only partly by the NHE inhibitor 5-(N,N-dimethyl)-amiloride (DMA), indicating the INCX increase was primarily mediated by the MEK/mitogen-activated protein kinase (MAPK) pathway, and partially through activation of NHE. F2 attenuated the H2O2-induced INCX increase in a concentration-dependent manner. To determine whether pathway inhibition was H2O2-specific, we examined the ability of F2 to inhibit MEK/ERK activation by epidermal growth factor (EGF), and NHE activation by angiotensin II. F2 not only inhibited H2O2-induced and EGF-induced MEK/ERK activation, but also completely blocked both H2O2-induced and angiotensin II-induced increases in NHE activity, suggesting that F2 directly inhibits MEK/ERK and NHE activation. These results show that F2 exerts multiple inhibitions on the signal-transduction pathway involved in H2O2-induced INCX increase, providing an additional mechanism for F2 alleviating intracellular Ca2+ overload to protect against myocardial I/R injury. Keywords: N-n-butyl haloperidol, hydrogen peroxide, Na+/Ca2+ exchanger, Na+/H+ exchanger

PURPOSE: The present clinical study assessed the feasibility of extensive pedicled supraclavicular fasciocutaneous island flaps combined with extended vertical lower trapezius island myocutaneous flaps for large, full-thickness cheek defect reconstruction after ablative oral cancer surgery. PATIENTS AND METHODS: A retrospective review of data from consecutive patients requiring extensive pedicled supraclavicular fasciocutaneous island flaps and the extended vertical lower trapezius island myocutaneous flap to provide both an inner and an outer lining for major full-thickness cheek defects after oncologic resection. RESULTS: Eight patients had advanced oral squamous cell carcinoma. All patients had combined bone and extensive soft-tissue defects. The extensive pedicled supraclavicular fasciocutaneous island flap with a skin paddle measuring 10 x 8 cm to 14 x 10 cm and the extended vertical lower trapezius island myocutaneous flap with a skin paddle measuring 25 x 10 cm to 15 x 8 cm were used to reconstruct the major through-and-through defects. No major complications occurred in any patient. The patients were followed up for 6 to 20 months; 6 patients were living with no evidence of disease, 1 was living with disease, and 1 had died of local recurrence. CONCLUSIONS: The combined use of the extensive pedicled supraclavicular fasciocutaneous island flap with an extended vertical lower trapezius island myocutaneous flap to reconstruct major through-and-through cheek soft defects is reliable and an excellent alternative to other pedicles, even microsurgical free flaps, for patients who have previously undergone radiotherapy and surgery of the head and neck. [ABSTRACT FROM AUTHOR]

Sluggish interfacial water dissociation and the O 2 evolution reaction (OER) kinetics are the main obstacles that limit the photocatalytic overall water-splitting performance. A molten salt modulation of potassium-nitrogen-carbon is herein demonstrated as the formation of highly crystalline potassium-doped poly(triazine imide) (KPTI). The in situ X-ray diffraction patterns and theoretical calculation show that the KCl melt can significantly reduce the free energy for the polycondensation of triazine building blocks owing to the formation of a kinetically stable KPTI. Benefiting from the presence of potassium-carbon-nitrogen moiety, the catalyst not only weakens the excitonic confinement to improve the separation efficiency of photogenerated charge carriers but also enhances the stability of carbon sites by suppressing the undesired C═O formation. Moreover, KPTI accelerates water dissociation by forming interfacial K·H 2 O clusters with an ordered structure, which supplies sufficient protons for the H 2 evolution reaction and lowers the energy barrier to enhance the kinetics of OER. Therefore, a stable photocatalytic overall water-splitting performance can be achieved over KPTI with a stoichiometric generation of products (H 2 and O 2 ). Life cycle assessment shows that a carbon-neutral scenario can be achieved on KPTI production in the near term with an increase in green power in the electricity grid.

Dihydrogen complexes, which retain the H-H bond, have been extensively studied in molecular science and found to be prevalent in homogeneous and enzymatic catalysis. However, their counterparts in heterogeneous catalysis, specifically nondissociative chemisorbed dihydrogen binding on the catalyst surface, are rarely reported experimentally. This scarcity is due to the complexity of typical material surfaces and the lack of effective characterization techniques to prove and distinguish various dihydrogen binding modes. Herein, using high-pressure operando solid-state NMR technology, we report the first unambiguous experimental observation of activated dihydrogen binding on a reduced ceria catalyst through interactions with surface oxygen vacancies. By employing versatile NMR structural and dynamical analysis methods, we establish a proportional relationship between the degree of ceria surface reduction and dihydrogen binding, as evidenced by NMR observations of H-D through-bond coupling ( J HD ), T 1 relaxation, and proton isotropic chemical shifts. In situ NMR analysis further reveals the participation of bound dihydrogen species in a room-temperature ethylene hydrogenation reaction. The remarkable similarities between surface-activated dihydrogen in heterogeneous catalysis and dihydrogen model molecular complexes can provide valuable insights into the hydrogenation mechanism for many other solid catalysts, potentially enhancing hydrogen utilization.

Objectives: To explore the spatial distribution characteristics, trend changes, and spatial clustering of esophageal cancer among residents in China at the county (city, district) scale, a spatial epidemiological approach was used, with the aim of providing localized evidence for the prevention and treatment of esophageal cancer in China. Methods: The data source was the incidence (crude rate) and mortality (crude rate) of esophageal cancer from 2005 to 2016 in the 2008-2019 edition of China Cancer Registration Annual Report published by the National Cancer Center. The Joinpoint model was used for time trend analysis. The tumor registration area in 2016 was selected as the study area for spatial feature analysis, with a total of 487 counties (cities and districts), covering 27.6% of the national population. Spatial autocorrelation analysis was performed to reveal spatial distribution characteristics by using Arcgis 10.6 software, and spatial scanning statistics was used to analyze spatial clustering characteristics by using SaTScan 9.5 software. The log-likelihood ratio ( LLR ) and relative risk ( RR ) were calculated in different windows, and the region with the largest LLR value represented the most likely cluster. Results: From 2005 to 2016, the incidence and mortality rate of esophageal cancer in China showed a trend of increasing at first and then decreasing. The incidence and mortality rate of esophageal cancer in 2016 were characterized by spatial positive correlation. High incidence and high mortality were mainly concentrated in the areas through which the Huaihe River flowed. The primary clusters (taking high incidence rate as an example LLR =6 374.41, RR =2.37, P ＜0.001) were mainly distributed in Jiangsu, Anhui and Shandong in eastern China and eastern Henan and southern Hebei in central China, and secondary clusters (taking high incidence rate as an example LLR =1 971.19, RR =1.91, P ＜0.001) in Gansu, Ningxia Hui Autonomous Region, Shaanxi, Sichuan and other central and western regions. Conclusions: The incidence and mortality of esophageal cancer in China have decreased since 2010. The disease burden of esophageal cancer has obvious spatial differences, and measures should be taken according to local conditions in high-risk cluster areas such as the Huaihe River basin.

With the imbalance of intestinal microbiota, the body will then face an inflammatory response, which has serious implications for human health. Bodily allergies, injury or pathogens infections can trigger or promote inflammation and alter the intestinal environment. Meanwhile, excessive changes in the intestinal environment cause the imbalance of microbial homeostasis, which leads to the proliferation and colonization of opportunistic pathogens, invasion of the body's immune system, and the intensification of inflammation. Some natural compounds and gut microbiota and metabolites can reduce inflammation; however, the details of how they interact with the gut immune system and reduce the gut inflammatory response still need to be fully understood. The review focuses on inflammation and intestinal microbiota imbalance caused by pathogens. The body reacts differently to different types of pathogenic bacteria, and the ingestion of pathogens leads to inflamed gastrointestinal tract disorders or intestinal inflammation. In this paper, unraveling the interactions between the inflammation, pathogenic bacteria, and intestinal microbiota based on inflammation caused by several common pathogens. Finally, we summarize the effects of intestinal metabolites and natural anti-inflammatory substances on inflammation to provide help for related research of intestinal inflammation caused by pathogenic bacteria., 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 GmbH. All rights reserved.)

The surface frustrated Lewis pairs (SFLPs) open up new opportunities for substituting noble metals in the activation and conversion of stable molecules. However, the applications of SFLPs on a larger scale are impeded by the complex construction process, low surface density, and sensitivity to the reaction environment. Herein, wurtzite-structured crystals such as GaN, ZnO, and AlP are found for developing natural, dense, and stable SFLPs. It is revealed that the SFLPs can naturally exist on the (100) and (110) surfaces of wurtzite-structured crystals. All the surface cations and anions serve as the Lewis acid and Lewis base in SFLPs, respectively, contributing to the surface density of SFLPs as high as 7.26×10 14  cm -2 . Ab initio molecular dynamics simulations indicate that the SFLPs can keep stable under high temperatures and the reaction atmospheres of CO and H 2 O. Moreover, outstanding performance for activating the given small molecules is achieved on these natural SFLPs, which originates from the optimal orbital overlap between SFLPs and small molecules. Overall, these findings not only provide a simple method to obtain dense and stable SFLPs but also unfold the nature of SFLPs toward the facile activation of small molecules., (© 2024 Wiley-VCH GmbH.)

The contribution of litterfall nutrient return to the maintenance of soil carbon pool and nutrient cycling is a crucial aspect of forest ecosystem functioning. Taking 21 tree species in subtropical young plantations as subjects, we investigated the correlation between litterfall nutrient return characteristics and functional traits of leaf and root and. The results showed notable variations in litterfall production, standing crop, and nutrient return across all the examined tree species. Mytilaria laosensis exhibited the highest litterfall production (689.2 g·m -2 ·a -1 ) and standing crop (605.1 g·m -2 ), while Cryptomeria fortunei demonstrated the lowest litterfall production (36.0 g·m -2 ·a -1 ) and standing crop (10.0 g·m -2 ). The nitrogen and phosphorus return amounts of 21 species ranged from 3.0 to 48.3 kg·hm -2 and from 0.1 to 2.0 kg·hm -2 , respectively. Castanopsis fissa demonstrated the highest nitrogen return, while Liquidambar formosana exhibited the highest phosphorus return. C. fortunei had the lowest nitrogen and phosphorus return. Results of the stepwise regression analysis indicated that litterfall production exhibited a significant negative correlation with leaf nitrogen content and leaf dry matter content, and a significant positive correlation with fine root tissue density. Additionally, leaf nitrogen content, leaf dry matter content, and specific root length had a significant negative impact on standing crop. The structural equation modelling results indicated that leaf dry matter content had a direct or indirect negative effect on nitrogen return amount through the reduction of litterfall production. Conversely, fine root tissue density had a significant positive impact on nitrogen return amount by increasing litter leaf nitrogen content. Both leaf nitrogen content and leaf dry matter content had direct or indirect negative effects on phosphorus return amount through the reduction of litterfall production. In conclusion, the tree species with low leaf nitrogen content and dry matter content, as well as high fine root tissue density, was recommended for the establishment of plantations in the subtropical zone in order to enhance nutrient cycling through litter decomposition and improve soil fertility and forest productivity.

The excellent reactivity of frustrated Lewis pairs (FLP) to activate small molecules has gained increasing attention in recent decades. Though the development of surface FLP (SFLP) is prompting the application of FLP in the chemical industry, the design of SFLP with superior activity, high density, and excellent stability for small-molecule activation is still challenging. Herein, we review the progress of designing SFLP by surface engineering, screening natural SFLP, and the dynamic formation of SFLP from theoretical perspectives. We highlight the breakthrough in fine-tuning the activity, density, and stability of the designed SFLP studied by using computational methods. We also discuss future challenges and directions in designing SFLP with outstanding capabilities for small-molecule activation.

RNA cytidine-to-uridine editing is essential for plant organellar gene expression. Pentatricopeptide repeat (PPR)-E+ proteins have been proposed to bind to target sites and recruit the cytidine deaminase AtDYW2, facilitated by AtNUWA. Here we analyze the function of ZmNUWA, ZmDYW2A, and ZmDYW2B and their relationships with other editing factors in maize. The zmdyw2a and zmdyw2b single mutants are normal, but the zmdyw2a::zmdyw2b and zmnuwa mutants are severely arrested in seed development. ZmNUWA, ZmDYW2A, and ZmDYW2B are dual localized in mitochondria and plastids. Loss of ZmNUWA decreases the editing at 99 mitochondrial sites and 8 plastid sites. Surprisingly, loss of ZmDYW2A:ZmDYW2B affects almost the same set of sites targeted by PPR-E+ proteins. ZmNUWA interacts with ZmDYW2A and ZmDYW2B, suggesting that ZmNUWA recruits ZmDYW2A/2B in the editing of PPR-E+-targeted sites in maize. Further protein interaction analyses show that ZmNUWA and ZmDYW2A/2B interact with ZmMORF1, ZmMORF8, ZmMORF2, and ZmMORF9 and that ZmOZ1 interacts with ZmORRM1, ZmDYW2A, ZmDYW2B, ZmMORF8, and ZmMORF9. These results suggest that the maize mitochondrial PPR-E+ editosome contains PPR-E+, ZmDYW2A/2B, ZmNUWA, and ZmMORF1/8, whereas the plastid PPR-E+ editosome is composed of PPR-E+, ZmDYW2A/2B, ZmNUWA, ZmMORF2/8/9, ZmORRM1, and ZmOZ1., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

IgA nephropathy (IgAN) is characterized by glomerular deposition of immune complexes (ICs) consisting of IgA1 with O -glycans deficient in galactose (Gd-IgA1) and Gd-IgA1-specific IgG autoantibodies. These ICs induce kidney injury, and in the absence of disease-specific therapy, up to 40% of patients with IgAN progress to kidney failure. IgA1 with its clustered O -glycans is unique to humans, which hampered development of small-animal models of IgAN. Here, we used a model wherein engineered ICs (EICs) formed from human Gd-IgA1 and recombinant human IgG autoantibody are injected into nude mice to induce glomerular injury mimicking human IgAN. In this model, we assessed the protective effects of sparsentan, a single-molecule dual endothelin angiotensin receptor antagonist (DEARA) versus vehicle on EIC-induced glomerular proliferation and dysregulation of gene expression in the kidney. Oral administration of sparsentan (60 or 120 mg/kg daily) to mice intravenously injected with EIC attenuated the EIC-induced glomerular hypercellularity. Furthermore, analysis of changes in the whole kidney transcriptome revealed that key inflammatory and proliferative biological genes and pathways that are upregulated in this EIC model of IgAN were markedly reduced by sparsentan, including complement genes, integrin components, members of the mitogen-activated protein kinase family, and Fc receptor elements. Partial overlap between mouse and human differentially expressed genes in IgAN further supported the translational aspect of the immune and inflammatory components from our transcriptional findings. In conclusion, our data indicate that in the mouse model of IgAN, sparsentan targets immune and inflammatory processes leading to protection from mesangial hypercellularity. NEW & NOTEWORTHY The mechanisms by which deposited IgA1 immune complexes cause kidney injury during early phases of IgA nephropathy are poorly understood. We used an animal model we recently developed that involves IgA1-IgG immune complex injections and determined pathways related to the induced mesangioproliferative changes. Treatment with sparsentan, a dual inhibitor of endothelin type A and angiotensin II type 1 receptors, ameliorated the induced mesangioproliferative changes and the associated alterations in the expression of inflammatory genes and networks.

Tight junction (TJ) proteins establish a physical barrier between epithelial cells, playing a crucial role in maintaining tissue homeostasis by safeguarding host tissues against pathogens, allergens, antigens, irritants, etc. Recently, an increasing number of studies have demonstrated that abnormal expression of TJs plays an essential role in the development and progression of inflammatory airway diseases, including chronic obstructive pulmonary disease, asthma, allergic rhinitis, and chronic rhinosinusitis (CRS) with or without nasal polyps. Among them, CRS with nasal polyps is a prevalent chronic inflammatory disease that affects the nasal cavity and paranasal sinuses, leading to a poor prognosis and significantly impacting patients' quality of life. Its pathogenesis primarily involves dysfunction of the nasal epithelial barrier, impaired mucociliary clearance, disordered immune response, and excessive tissue remodeling. Numerous studies have elucidated the pivotal role of TJs in both the pathogenesis and response to traditional therapies in CRS. We therefore to review and discuss potential factors contributing to impair and repair of TJs in the nasal epithelium based on their structure, function, and formation process., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Direct methane conversion (DMC) to oxygenates at low temperature is of great value but remains challenging due to the high energy barrier for C-H bond activation. Here, we report that in situ decoration of Pd 1 -ZSM-5 single atom catalyst (SAC) by CO molecules significantly promoted the DMC reaction, giving the highest turnover frequency of 207 h -1 ever reported at room temperature and ~100 % oxygenates selectivity with H 2 O 2 as oxidant. Combined characterizations and DFT calculations illustrate that the C-atom of CO prefers to coordinate with Pd 1 , which donates electrons to the Pd 1 -O active center (L-Pd 1 -O, L=CO) generated by H 2 O 2 oxidation. The correspondingly improved electron density over Pd-O pair renders a favorable heterolytic dissociation of C-H bond with low energy barrier of 0.48 eV. Applying CO decoration strategy to M 1 -ZSM-5 (M=Pd, Rh, Ru, Fe) enables improvement of oxygenates productivity by 3.2-11.3 times, highlighting the generalizability of this method in tuning metal-oxo electronic structure of SACs for efficient DMC process., (© 2024 Wiley‐VCH GmbH.)

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32-55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26-58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP) causes progressive vision loss and is potentially incurable, accounting for 25% of adRP cases. Studies on RHO-adRP mechanism were at large based on the biochemical and cellular properties, especially class-3. Nonetheless, the absence of an appropriate model for class-3 RHO-adRP has impeded comprehensive exploration. Here, induced pluripotent stem cells (iPSCs) were generated from a healthy control and two sibling RP patients with the same point mutation, c.403C>T (p.R135W). The first three-dimensional (3D) retinal organoid model of a class-3 RHO point mutation from patient-derived iPSCs was generated. Significant defects were observed in rod photoreceptors in terms of localization, morphology, transcriptional profiling and single cell resolution, to better understand the human disease resulting from RHO mutations from a developmental perspective. This first human model of class-3 RHO-adRP provides a representation of patient's retina in vitro and displays features of RHO-adRP retinal organoids relevant for therapeutic development., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Aims: The incidence and mortality of hepatocellular carcinoma (HCC) are increasing. It is urgent to develop more effective HCC biomarkers for diagnosis and treatment. This project intends to verify the expression of enhancer of zeste 1 polycomb repressive complex 2 subunit (EZH1) and its mechanism in HCC., Methods: This study integrates global microarray and high-throughput sequencing datasets, combined with internal immunohistochemistry, to analyze the expression and prognostic value of EZH1 in HCC. Functional enrichment analysis was conducted to investigate transcriptional targets, which were achieved by intersecting HCC over-expressed genes, EZH1 co-expressed genes and putative transcriptional targets. The relationship between EZH1 and anticancer drugs was detected by drug sensitivity analysis., Results: In this study, 84 datasets from 40 platforms (3,926 HCC samples and 3,428 non-cancerous liver tissues) were included to show the high expression of EZH1 in HCC. Immunohistochemistry with 159 HCC samples and 62 non-HCC samples confirmed the high expression level. HCC patients with high EZH1 expression had worse survival prognoses. Gene ontology and Reactome analysis revealed that metabolism-related pathways, including autophagy, are critical for HCC. Interestingly, as one of the EZH1 potential transcriptional targets, autophagy-related 7 (ATG7) appeared in the above pathways. ATG7 was positively correlated with EZH1, upregulated in HCC, and mediated poor prognosis. Upregulation of EZH1 was found to be in contact with HCC anti-tumor drug resistance., Conclusions: The upregulation of EZH1 expression can promote the occurrence of HCC and lead to poor clinical progression and drug resistance; these effects may be mediated by regulating ATG7.

An investigation on the secondary metabolites from a rice culture broth of the endophytic fungus Neurospora terricola HDF-Br-2 derived from the vulnerable conifer Pseudotsuga gaussenii led to the isolation and characterization of 34 structurally diverse polyketides (1-34). Seven of them are previously undescribed, including five unprecedented dihydropyran-containing (terricoxanthones A-E, 1-5, resp.) and one rare tetrahydrofuran-containing (terricoxanthone F, 6) dimeric xanthones. The structures were elucidated by spectroscopic methods and single-crystal X-ray diffraction analyses. Terricoxanthones each were obtained as a racemic mixture. Their plausible biosynthetic relationships were briefly proposed. Compounds 6, aspergillusone A (8), and alatinone (27) displayed considerable inhibition against Candida albicans with MIC values of 8-16 μg/mL. 4-Hydroxyvertixanthone (12) and 27 exhibited significant inhibitory activities against Staphylococcus aureus, with MIC values of 4-8 μg/mL. Furthermore, compounds 8 and 27 could disrupt biofilm of S. aureus and C. albicans at 128 μg/mL. The findings not only extend the skeletons of xanthone dimers and contribute to the diversity of metabolites of endophytes associated with the endangered Chinese conifer P. gaussenii, but could further reveal the important role of protecting plant species diversity in support of chemical diversity and potential sources of new therapeutics., 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.)

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) constitutes a life-threatening condition, and identifying the ruptured aneurysm is essential for further therapy. This study aimed to evaluate the diagnostic accuracy of hypo-attenuating berry sign (HBS) observed on computed tomography (CT) scan in distinguishing ruptured aneurysms., Methods: In this diagnostic accuracy study, patients who had SAH and underwent non-enhanced brain CT scan were recruited. The HBS was defined as a hypo-attenuating area with an identifiable border in the blood-filled hyper-dense subarachnoid space. The screening performance characteristics of HBS in identifying ruptured aneurysms were calculated considering the digital subtraction angiography (DSA) as the gold standard., Results: A total of 129 aneurysms in 131 patients were analyzed. The overall sensitivity and specificity of HBS in the diagnosis of aneurysms were determined to be 78.7% (95%CI: 73.1% - 83.4%) and 70.7% (95%CI: 54.3% - 83.4%), respectively. Notably, the sensitivity increased to 90.9% (95%CI: 84.3% - 95.0%) for aneurysms larger than 5mm. The level of inter-observer agreement for assessing the presence of HBS was found to be substantial (kappa=0.734). The diagnostic accuracy of HBS in individuals exhibited enhanced specificity, sensitivity, and reliability when evaluating patients with a solitary aneurysm or assessing ruptured aneurysms. The multivariate logistic regression analysis revealed a statistically significant relationship between aneurysm size and the presence of HBS (odds ratios of 1.667 (95%CI: 1.238 - 2.244; p < 0.001) and 1.696 (95%CI: 1.231 - 2.335; p = 0.001) for reader 1 and reader 2, respectively)., Conclusions: The HBS can serve as a simple and easy-to-use indicator for identifying a ruptured aneurysm and estimating its size in SAH patients.   ., Competing Interests: The authors declare that they have no conflicts of interest.

The design and synthesis of metal-organic frameworks (MOFs) as photocatalytic molecular reactors for varied reactions have drawn great attention. In this work, we designed a novel photoactive perylenediimides-based (PDI) carboxylate ligand N,N'-di(3',3",5',5"-tetrakis(4-carboxyphenyl))-1,2,6,7-tetrachloroperylene-3,4,9,10-tetracarboxylic acid diimide (Cl-PDI-TA) and use it to successfully synthesize a novel Zr(IV)-based MOF 1 constructed from [Zr 6 O 8 (H 2 O) 8 ] 8+ clusters bridged by Cl-PDI-TA ligands. Structural analysis revealed that Zr-MOF 1 manifests a 3D framework with (4,8)-connected csq topology and possesses triangular channels of ~17 Å and mesoporous hexagonal channels of ~26 Å along c-axis. Moreover, the synthesized Zr-MOF 1 exhibits visible-light absorption and efficient photoinduced free radical generation property, making it a promising photocatalytic molecular reactor. When Zr-MOF 1 was used as a photocatalyst for the aerobic oxidation of sulfides under irradiation of visible light, it could afford the corresponding sulfoxides with high yield and selectivity. Experimental results demonstrated that the substrate sulfides could be fixed in the pores of 1 and directly transformed to the products sulfoxides in the solid state. Furthermore, the mechanism for the photocatalytic transformation was also investigated and the results revealed that the singlet oxygen ( 1 O 2 ) and superoxide radical (O 2 ⋅ - ) generated by the energy transfer and electron transfer from the photoexcited Zr-MOF to oxidants were the main active species for the catalytic reactions. This work offers a perceptive comprehension of the mechanism in PDI-based MOFs for further study on photocatalytic reactions., (© 2023 Wiley-VCH GmbH.)

Different types of cells uptake fatty acids in response to different stimuli or physiological conditions; however, little is known about context-specific regulation of fatty acid uptake. Here, we show that muscle injury induces fatty acid uptake in muscle stem cells (MuSCs) to promote their proliferation and muscle regeneration. In humans and mice, fatty acids are mobilized after muscle injury. Through CD36, fatty acids function as both fuels and growth signals to promote MuSC proliferation. Mechanistically, injury triggers the translocation of CD36 in MuSCs, which relies on dynamic palmitoylation of STX11. Palmitoylation facilitates the formation of STX11/SNAP23/VAMP4 SANRE complex, which stimulates the fusion of CD36- and STX11-containing vesicles. Restricting fatty acid supply, blocking fatty acid uptake, or inhibiting STX11 palmitoylation attenuates muscle regeneration in mice. Our studies have identified a critical role of fatty acids in muscle regeneration and shed light on context-specific regulation of fatty acid sensing and uptake., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Forest type and stand age are important biological factors affecting soil enzyme activities. However, the changes in soil enzyme activities across stand ages and underlying mechanisms under the two forest restoration strate-gies of plantations and natural secondary forests remain elusive. In this study, we investigated the variations of four soil enzyme activities including cello-biohydrolase (CBH), β-1,4-glucosidase (βG), acid phosphatase (AP) and β-1,4-N-acetylglucosaminidase (NAG), which were closely associated with soil carbon, nitrogen, and phosphorus cycling, across Cunninghamia lanceolata plantations and natural secondary forests (5, 8, 21, 27 and 40 years old). The results showed that soil enzyme activities showed different patterns across different forest types. The acti-vities of AP, βG and CBH in the C. lanceolata plantations were significantly higher than those in the natural secon-dary forests, and there was no significant difference in the NAG activity. In the plantations, AP activity showed a decreasing tendency with the increasing stand ages, with the AP activity in the 5-year-old plantations significantly higher than other stand ages by more than 62.3%. The activities of NAG and CBH decreased first and then increased, and βG enzyme activity fluctuated with the increasing stand age. In the natural secondary forests, NAG enzyme activity fluctuated with the increasing stand age, with that in the 8-year-old and 27-year-old stand ages being significantly higher than the other stand ages by more than 14.9%. βG and CBH enzyme activities increased first and then decreased, and no significant difference was observed in the AP activity. Results of the stepwise regression analyses showed that soil predictors explained more than 34% of the variation in the best-fitting models predicting soil enzyme activities in the C. lanceolata plantations and natural secondary forests. In conclusion, there would be a risk of soil fertility degradation C. lanceolata plantations with the increasing stand age, while natural secondary forests were more conducive to maintaining soil fertility.

Purpose: Colchicine, a multipotent anti-inflammatory drug, has been reported to alleviate cardiac remodeling and improve cardiac function after acute myocardial infarction (AMI). However, the underlying mechanism remains incompletely understood. Because neutrophils extracellular traps (NETs) enhance inflammation and participate in myocardial ischemia injury, and colchicine can inhibit NETosis, we thus aimed to determine whether colchicine exerts cardioprotective effects on AMI via suppressing NETs., Methods: Adult C57BL/6 mice were subjected to permanent ligation of the left anterior descending coronary artery and treated with colchicine (0.1 mg/kg/day) or Cl-amidine (10 mg/kg/day) for 7 or 28 days after AMI. Cardiac function was evaluated by echocardiography, and NETs detected by immunofluorescence. ROS production was detected using 2',7'-dichlorodihydrofluorescein diacetates (DCFH-DA) fluorometry. Intracellular Ca 2+ concentration was assessed by a fluorometric ratio technique., Results: We found that colchicine treatment significantly increased mice survival (89.8% in the colchicine group versus 67.9% in control, n = 32 per group; log-rank test, p < 0.05) and improved cardiac function at day 7 (left ventricular ejection fraction (LVEF): 28.0 ± 9.2% versus 12.6 ± 3.9%, n = 8 per group; p < 0.001) and at day 28 (LVEF: 26.2 ± 7.2% versus 14.8 ± 6.7%, n = 8 per group; p < 0.001) post-AMI. In addition, the administration of colchicine inhibited NETs formation and inflammation. Furthermore, colchicine inhibited NETs formation by reducing NOX2/ROS production and Ca 2+ influx. Moreover, prevention of NETs formation with Cl-amidine significantly alleviated AMI-induced cardiac remodeling., Conclusions: Colchicine inhibited NETs and cardiac inflammation, and alleviated cardiac remodeling after acute myocardial infarction., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: As a critical component of the epithelial barrier, tight junctions (TJs) are essential in nasal mucosa against pathogen invasion. However, the function of TJs has rarely been reported in nasal inverted papilloma (NIP). This study aims to investigate the potential factors of TJs' abnormality in NIP., Methods: We assessed the expression of ZO-1, occludin, claudin-1, claudin-3, and claudin-7 in healthy controls and NIP by real-time quantitative polymerase chain reaction and immunofluorescent staining. The correlation between TJs expression and neutrophil count, T H 1/T H 2/T H 17 and regulatory T cell biomarkers, and the proportion of nasal epithelial cells was investigated., Results: Upregulation of ZO-1, occludin, claudin-1, and claudin-7, along with downregulation of claudin-3, was found in NIP compared to control (all p < 0.05). An abnormal proportion with a lower number of ciliated cells (control vs. NIP: 37.60 vs. 8.67) and goblet cells (12.52 vs. 0.33) together with a higher number of basal cells (45.58 vs. 124.00) in NIP. Meanwhile, claudin-3 was positively correlated with ciliated and goblet cells (all p < 0.01). Additionally, neutrophils were excessively infiltrated in NIP, negatively correlated with ZO-1, but positively with claudin-3 (all p < 0.05). Furthermore, FOXP3, IL-10, TGF-β1, IL-5, IL-13, and IL-22 levels were induced in NIP (all p < 0.01). Occludin level was negatively correlated with IL-10, IL-5, IL-13, and IL-22, whereas ZO-1 was positively with TGF-β1 (all p < 0.05)., Conclusion: Nasal epithelial barrier dysfunction with TJs anomalies is commonly associated with abnormal proliferation and differentiation of epithelial cells and imbalance of immune and inflammatory patterns in NIP., Level of Evidence: NA Laryngoscope, 134:552-561, 2024., (© 2023 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Explore the relationship between tip of the left bundle branch pacing lead and anatomic location of left bundle branch as well as the mechanism of left bundle branch current of injury. To clarify the clinical value of left bundle branch current of injury during operation. Methods: The pacing leads were implanted in the hearts of two living swines. Intraoperative electrophysiological study confirmed that the left bundle branch or only the deep left ventricular septum was captured at low output. Immediately after operation, the gross specimen of swine hearts was stained with iodine to observe the gross distribution of His-purkinje conduction system on the left ventricular endocardium and its relationship with the leads. Subsequently, the swine hearts were fixed with formalin solution, and the pacing leads were removed after the positions were marked. The swine hearts were then sectioned and stained with Masson and Goldner trichrome, and the relationship between the anatomic location of the conduction system and the tip of the lead was observed under a light microscope. Results: After iodine staining of the specimen, the His-purkinje conduction system was observed with the naked eye in a net-like distribution, and the lead tip was screwed deeply and fixed in the left bundle branch area of the left ventricular subendocardium in the ventricular septum. Masson and Goldner trichrome staining showed that left bundle branch pacing lead directly passed through the left bundle branch when there was left bundle branch potential with left bundle branch current of injury, while it was not directly contact the left bundle branch when there was left bundle branch potential without left bundle branch current of injury. Conclusion: The left bundle branch current of injury observed on intracardiac electrocardiogram during His-purkinje conduction system pacing suggests that the pacing lead directly contacted the conduction bundle or its branches, therefore, the captured threshold was relatively low. Left bundle branch current of injury can be used as an important anatomic and electrophysiological evidence of left bundle branch capture.

Introduction: Galactose-deficient IgA1 (Gd-IgA1) plays a key role in the pathogenesis of IgA nephropathy (IgAN). Tonsillectomy has been beneficial to some patients with IgAN, possibly due to the removal of tonsillar cytokine-activated cells producing Gd-IgA1. To test this hypothesis, we used immortalized IgA1-producing cell lines derived from tonsils of patients with IgAN or obstructive sleep apnea (OSA) and assessed the effect of leukemia inhibitory factor (LIF) or oncostatin M (OSM) on Gd-IgA1 production., Methods: Gd-IgA1 production was measured by lectin enzyme-linked immunosorbent assay; JAK-STAT signaling in cultured cells was assessed by immunoblotting of cell lysates; and validated by using small interfering RNA (siRNA) knock-down and small-molecule inhibitors., Results: IgAN-derived cells produced more Gd-IgA1 than the cells from patients with OSA, and exhibited elevated Gd-IgA1 production in response to LIF, but not OSM. This effect was associated with dysregulated STAT1 phosphorylation, as confirmed by STAT1 siRNA knock-down. JAK2 inhibitor, AZD1480 exhibited a dose-dependent inhibition of the LIF-induced Gd-IgA1 overproduction. Unexpectedly, high concentrations of AZD1480, but only in the presence of LIF, reduced Gd-IgA1 production in the cells derived from patients with IgAN to that of the control cells from patients with OSA. Based on modeling LIF-LIFR-gp130-JAK2 receptor complex, we postulate that LIF binding to LIFR may sequester gp130 and/or JAK2 from other pathways; and when combined with JAK2 inhibition, enables full blockade of the aberrant O -glycosylation pathways in IgAN., Conclusion: In summary, IgAN cells exhibit LIF-mediated overproduction of Gd-IgA1 due to abnormal signaling. JAK2 inhibitors can counter these LIF-induced effects and block Gd-IgA1 synthesis in IgAN., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Objective: To analyze the association between different treatment timings and adverse neonatal outcomes (premature birth, death, congenital syphilis) in syphilis-infected pregnant women. Methods: The National Management Information System for Prevention of HIV, Syphilis and HBV Mother-to-Child Transmission was used to collect information on the detection and treatment of syphilis-infected pregnant women and their newborns in Guangdong Province from October 2011 to December 2021. According to the gestational weeks of syphilis-infected pregnant women receiving penicillin treatment for the first time, they were divided into four groups: treatment in the first trimester, treatment in the second trimester, treatment in the third trimester, and no treatment during pregnancy. Multivariate logistic regression was used to analyze the association between different treatment timings and adverse neonatal outcomes in syphilis-infected pregnant women. Results: A total of 22 483 syphilis-infected pregnant women were included. The number of pregnant women who started treatment in the first trimester, second trimester, and third trimester and did not receive treatment during pregnancy were 4 549 (20.23%), 8 719 (38.78%), 2 235 (9.94%) and 6 980 (31.05%), respectively. Compared with pregnant women who started treatment in the first trimester, pregnant women who did not receive anti-syphilis treatment during pregnancy had increased risks of neonatal preterm birth ( OR =1.42, 95% CI : 1.24-1.62), death ( OR =4.27, 95% CI : 1.64-14.69) and congenital syphilis ( OR =12.26, 95% CI : 6.35-27.45). At the same time, the risk of congenital syphilis in the newborns of pregnant women who started anti-syphilis treatment in the second trimester ( OR =2.68, 95% CI : 1.34-6.16) and third trimester ( OR =6.27, 95% CI : 2.99-14.80) also increased. Conclusion: Early initiation of anti-syphilis treatment during pregnancy in patients with syphilis can improve neonatal outcomes.

The cell cycle regulator cyclin D3 (CCND3) is highly expressed in multiple myeloma (MM) and it promotes MM cell proliferation. After a certain phase of cell cycle, CCND3 is rapidly degraded, which is essential for the strict control of MM cell cycle progress and proliferation. In the present study, we investigated the molecular mechanisms regulating CCND3 degradation in MM cells. By utilizing affinity purification-coupled tandem mass spectrometry, we identified the deubiquitinase USP10 interacting with CCND3 in human MM OPM2 and KMS11 cell lines. Furthermore, USP10 specifically prevented CCND3 from K48-linked polyubiquitination and proteasomal degradation, therefore enhancing its activity. We demonstrated that the N-terminal domain (aa. 1-205) of USP10 was dispensable for binding to and deubiquitinating CCND3. Although Thr283 was important for CCND3 activity, it was dispensable for CCND3 ubiquitination and stability modulated by USP10. By stabilizing CCND3, USP10 activated the CCND3/CDK4/6 signaling pathway, phosphorylated Rb, and upregulated CDK4, CDK6 and E2F-1 in OPM2 and KMS11 cells. Consistent with these findings, inhibition of USP10 by Spautin-1 resulted in accumulation of CCND3 with K48-linked polyubiquitination and degradation that synergized with Palbociclib, a CDK4/6 inhibitor, to induce MM cell apoptosis. In nude mice bearing myeloma xenografts with OPM2 and KMS11 cells, combined administration of Spautin-l and Palbociclib almost suppressed tumor growth within 30 days. This study thus identifies USP10 as the first deubiquitinase of CCND3 and also finds that targeting the USP10/CCND3/CDK4/6 axis may be a novel modality for the treatment of myeloma., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: To compare the diagnostic value of cytobrush, ERCP-guided biopsy, SpyGlass direct visual impression and SpyGlass-guided biospy (SpyBite) in the differential diagnosis of benign and malignant bile duct strictures., Methods: The data of 1,008 patients who were clinically diagnosed with indeterminate biliary strictures and underwent ERCP-guided biopsy, cytobrush, SpyGlass direct visual impression or SpyBite at the First Affiliated Hospital of Nanchang University between January 2010 and December 2019 were collected and analyzed retrospectively. The final diagnose was determined by surgical pathological specimen or follow-up (Malignant stricture can be identified if the stricture showed malignant progression during one year of follow-up). The differential diagnostic value of the above endoscopic diagnostic methods was evaluated by means of sensitivity, specificity, accuracy, positive predictive value, negative predictive value, etc. and safety was evaluated by the incidence rate of adverse events., Results: In terms of sensitivity, standard biopsy group (48.6%) and SpyBite group (61.5%) were significantly higher than cytobrush group (32.0%), and visual impression group (100%) was significantly higher than any other group. As far as specificity was concerned, cytobrush group (99.0%), standard biopsy group (99.3%) and the SpyBite group (100%) were significantly higher than visual impression (55.6%), but there was no statistical difference among the three groups above. As far as accuracy was concerned, standard biopsy group (65.3%), and SpyBite group (80.0%) were significantly higher than cytobrush group (44.4%), and SpyBite group (80.0%) was significantly higher than visual impression group (54.8%). In terms of safety, visual impression group and SpyBite group were significantly higher than cytobrush group and standard biopsy group in post-ERCP cholangitis., Conclusion: SpyBite combined with SpyGlass-guided visual impression was better for differential diagnosis of benign and malignant bile duct strictures in terms of sensitivity and accuracy compared with conventional endoscopic diagnostic methods such as cytobrush and standard biopsy. Furthmore, the incidence rates of adverse events after SpyGlass examination was similar to those after conventional endoscopic diagnostic methods except for higher cholangitis, which could be controlled by antibiotics and might be avoided by adequate biliary drainage., 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 © 2023 Zhu, Huang, Wang, Yang, Hong, Yang, Yu, Cao, He and Chen.)

Purpose: The abnormal expression of tight junction (TJ) plays a vital role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, there is no appropriate tool to distinguish and diagnose epithelial barrier defects in clinical practice. This study aimed to evaluate the predictive value of claudin-3 for epithelial barrier dysfunction in CRSwNP., Methods: In this study, TJ protein levels were evaluated by real-time quantitative polymerase chain reaction, immunofluorescent, and immunohistochemistry staining in control subjects and CRSwNP patients. The receiver operating characteristic (ROC) curve was created to assess the predictive value of TJ breakdown in clinical outcomes. In vitro, human nasal epithelial cells were cultured at the air-liquid interface to analyze the transepithelial electrical resistance (TER) level., Results: The expression levels of occludin, tricellulin, claudin-3, and claudin-10 were decreased (all P < 0.05), and those of claudin-1 was increased ( P < 0.05) in CRSwNP patients as compared to healthy subjects. Additionally, claudin-3 and occludin levels were negatively correlated with the computed tomography score in CRSwNP (all P < 0.05), and the ROC curve indicated that the claudin-3 level had the most predictive accuracy in evaluating epithelial barrier disruption (area under the curve = 0.791, P < 0.001). Finally, the time-series analysis showed the highest correlation coefficient between TER and claudin-3 (cross-correlation function = 0.75)., Conclusion: In this study, we suggest that claudin-3 could be a valuable biomarker for predicting nasal epithelial barrier defects and disease severity in CRSwNP., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2023 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease.)

The immune system provides full protection for the body by specifically identifying 'self' and removing 'others'; thus protecting the body from diseases. The immune system includes innate immunity and adaptive immunity, which jointly coordinate the antitumor immune response. T cells, natural killer (NK) cells and tumor-associated macrophages (TAMs) are the main tumor-killing immune cells active in three antitumor immune cycle. Cancer immunotherapy focusses on activating and strengthening immune response or eliminating suppression from tumor cells in each step of the cancer-immunity cycle; thus, it strengthens the body's immunity against tumors. In this review, the antitumor immune cycles of T cells, natural killer (NK) cells and tumor-associated macrophages (TAMs) are discussed. Co-stimulatory and co-inhibitory molecules in the three activity cycles and the development of drugs and delivery systems targeting these molecules are emphasized, and the current state of the art of drug delivery systems for cancer immunotherapy are summarized., 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 © 2023 Yang, Yang, Huang, Li, Shi, Sun, Ma, Wang, Zhang, Yang, Zhao and Xu.)

Oomycetes, particularly those from the genus Phytophthora , are significant threats to global food security and natural ecosystems. Oxathiapiprolin (OXA) is an effective oomycete fungicide that targets an oxysterol binding protein (OSBP), while the binding mechanism of OXA is still unclear, which limits the pesticide design, induced by the low sequence identity of Phytophthora and template models. Herein, we generated the OSBP model of the well-reported Phytophthora capsici using AlphaFold 2 and studied the binding mechanism of OXA. Based on it, a series of OXA analogues were designed. Then, compound 2l , the most potent candidate, was successfully designed and synthesized, showing a control efficiency comparable to that of OXA. Moreover, field trial experiments showed that 2l exhibited nearly the same activity (72.4%) as OXA against cucumber downy mildew at 25 g/ha. The present work indicated that 2l could be used as a leading compound for the discovery of new OSBP fungicides.

When plates with edge cracks in the rolling process is straightened by cyclic tensile and compressive stress, the tip of edge crack always accompanied by stress concentration, which leads to crack propagation. In this paper, damage parameters are imported into the plate straightening model based on determining the GTN damage parameters of magnesium alloy materials by inverse finite element calibration method, the influence of different straightening process schemes and prefabricated V-shaped crack geometry on crack growth is analyzed through the way of the combination of simulation and straightening experiment. The results show that the peak values of equivalent stress and equivalent strain under each straightening roll appear at the crack tip. The value of longitudinal stress and equivalent stain decrease with the distance to crack tip becomes larger. The peak value of longitudinal stress appears when the crack circumferential angle is about 100°, and the crack tip is easy to form crack propagation; when the plate passes roll 2 and roll 4, the equivalent stress and strain concentration at the crack tip are most obvious; when the reduction reaches a certain degree, the void volume fraction (VVF) reaches the VVF of the material breaking; with the increase of the entrance reduction, the number of VVF at the crack tip which reaches the material fracture increases, and the length of crack propagation increases; the stress concentration at the tip of V-shaped crack with large length-width ratio is obvious, and the VVF is more likely to reach the VVF at the time of material fracture, crack initiates and propagates easily., (© 2023. The Author(s).)

Stroke usually causes prolonged or lifelong disability, owing to the permanent loss of infarcted tissue. Although a variety of stem cell transplantation has been explored to improve neuronal defect behavior by enhancing neuroplasticity, it remains unknown whether the infarcted tissue can be reconstructed. We here cultured human cerebral organoids derived from human pluripotent stem cells (hPSCs) and transplanted them into the junction of the infarct core and the peri-infarct zone of NOD-SCID mice subjected to stroke. Months later, we found that the grafted organoids survived well in the infarcted core, differentiated into target neurons, repaired infarcted tissue, sent axons to distant brain targets, and integrated into the host neural circuit and thereby eliminated sensorimotor defect behaviors of stroke mice, whereas transplantation of dissociated single cells from organoids failed to repair the infarcted tissue. Our study offers a new strategy for reconstructing infarcted tissue via organoids transplantation thereby reversing stroke-induced disability., (© 2023. The Author(s).)

This study aimed to explore the correlation of Golgi phosphoprotein 3 (GOLPH3) levels in papillary thyroid carcinoma (PTC) and papillary thyroid microcarcinoma (PTMC) with clinicopathologic features. GOLPH3 expression was determined by western blotting in solid tumors and the adjacent normal thyroid tissues. Mammalian target of rapamycin (mTOR) and Ki-67 were examined by immunohistochemical staining. Significantly higher levels of GOLPH3 protein were observed in PTC and PTMC compared with the adjacent normal thyroid tissues ( P <0.001). GOLPH3 level was positively associated with lymph node metastasis and clinical stage in PTC ( P <0.05) and utterly related to the clinical stage in PTMC ( P =0.012). No correlation was observed between GOLPH3 level and other clinicopathologic parameters such as sex, local invasion, tumor number, and tumor size. The expression level of GOLPH3 protein in mTOR-positive PTC was significantly higher than in mTOR-negative PTC ( P =0.002 in PTC, P =0.022 in PTMC) and positively correlated with Ki-67 proliferation index in PTC via Pearson correlation analysis ( r =0.353, P =0.007 in PTC; r =0.583, P <0.001 in PTMC). In conclusion, the relative expression level of GOLPH3 protein was significantly higher in PTC and PTMC than in normal thyroid tissues and increased with cancer severity. It may provide adjunctive information for diagnosing and predicting prognosis in patients with PTC or PTMC., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Stroke is a leading cause of adult disability worldwide, and better drugs are needed to promote functional recovery after stroke. Growing evidence suggests the critical role of network excitability during the repair phase for stroke recovery. Here, we show that β-hydroxybutyrate (β-HB), an essential ketone body (KB) component, is positively correlated with improved outcomes in patients with stroke and promotes functional recovery in rodents with stroke during the repair phase. These beneficial effects of β-HB depend on HDAC2/HDAC3-GABA transporter 1 (GAT-1) signaling-mediated enhancement of excitability and phasic GABA inhibition in the peri-infarct cortex and structural and functional plasticity in the ipsilateral cortex, the contralateral cortex, and the corticospinal tract. Together with available clinical approaches to elevate KB levels, our results offer a clinically translatable means to promote stroke recovery. Furthermore, GAT-1 can serve as a pharmacological target for developing drugs to promote functional recovery after stroke., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study is to assess the influence of cardiopulmonary coupling (CPC) based on RCMSE on the prediction of complications and death in patients with acute type A aortic dissection (ATAAD)., Background: The cardiopulmonary system may be nonlinearly regulated, and its coupling relationship with postoperative risk stratification in ATAAD patients has not been studied., Methods: This study was a single-center, prospective cohort study (ChiCTR1800018319). We enrolled 39 patients with ATAAD. The outcomes were in-hospital complications and all-cause readmission or death at 2 years., Results: Of the 39 participants, 16 (41.0%) developed complications in the hospital, and 15 (38.5%) died or were readmitted to the hospital during the two-year follow-up. When CPC-RCMSE was used to predict in-hospital complications in ATAAD patients, the AUC was 0.853 ( p  < 0.001). When CPC-RCMSE was used to predict all-cause readmission or death at 2 years, the AUC was 0.731 ( p  < 0.05). After adjusting for age, sex, ventilator support (days), and special care time (days), CPC-RCMSE remained an independent predictor of in-hospital complications in patients with ATAAD [adjusted OR: 0.8 (95% CI, 0.68-0.94)]., Conclusion: CPC-RCMSE was an independent predictor of in-hospital complications and all-cause readmission or death in patients with ATAAD., 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., (© 2023 Mao, Wen, Han, Dong, Shen, Huang and Xie.)

The compressed ultrafast photography (CUP) can capture non-repetitive time-evolving events at 7 × 10 13  fps, which is anticipated to find a diverse range of applications in physics, biomedical imaging, and materials science. The feasibility of diagnosing ultrafast phenomenon of Z-pinch by using the CUP has been analyzed in this article. Specifically, a dual-channel CUP design has been adopted for acquiring high quality reconstructed images and the strategies of identical masks, uncorrelated masks, and complementary masks have been compared. Furthermore, the image of the first channel was rotated by 90° to balance the spatial resolution between the sweep direction and the non-sweep direction. Both five synthetic videos and two simulated Z-pinch videos were chosen as the ground truth to validate this approach. The average peak signal to noise ratio of the reconstruction results is 50.55 dB for the self-emission visible light video and 32.53 dB for the laser shadowgraph video with unrelated masks (rotated channel 1). The simulation results show that the time-space-evolving process of plasma distribution can be well retold, and the phenomenon of plasma instability can be accurately diagnosed by the dual-channel CUP with unrelated masks (rotated channel 1). This study may promote the practical applications of the CUP in the field of accelerator physics.

Abdominal aortic aneurysm (AAA) is a dangerous vascular disease without any effective drug therapies so far. Emerging evidence suggests the phenotypic differences in perivascular adipose tissue (PVAT) between regions of the aorta are implicated in the development of atherosclerosis evidenced by the abdominal aorta more vulnerable to atherosclerosis than the thoracic aorta in large animals and humans. The prevalence of thoracic aortic aneurysms (TAA) is much less than that of abdominal aortic aneurysms (AAA). In this study we investigated the effect of thoracic PVAT (T-PVAT) transplantation on aortic aneurysm formation and the impact of T-PVAT on vascular smooth muscle cells. Calcium phosphate-induced mouse AAA model was established. T-PVAT (20 mg) was implanted around the abdominal aorta of recipient mice after removal of endogenous abdominal PVAT (A-PVAT) and calcium phosphate treatment. Mice were sacrificed two weeks after the surgery and the maximum external diameter of infrarenal aorta was measured. We found that T-PVAT displayed a more BAT-like phenotype than A-PVAT; transplantation of T-PVAT significantly attenuated calcium phosphate-induced abdominal aortic dilation and elastic degradation as compared to sham control or A-PVAT transplantation. In addition, T-PVAT transplantation largely preserved smooth muscle cell content in the abdominal aortic wall. Co-culture of T-PVAT with vascular smooth muscle cells (VSMCs) significantly inhibited H 2 O 2 - or TNFα plus cycloheximide-induced VSMC apoptosis. RNA sequencing analysis showed that T-PVAT was enriched by browning adipocytes and anti-apoptotic secretory proteins. We further verified that the secretome of mature adipocytes isolated from T-PVAT significantly inhibited H 2 O 2 - or TNFα plus cycloheximide-induced VSMC apoptosis. Using proteomic and bioinformatic analyses we identified cartilage oligomeric matrix protein (COMP) as a secreted protein significantly increased in T-PVAT. Recombinant COMP protein significantly inhibited VSMC apoptosis. We conclude that T-PVAT exerts anti-apoptosis effect on VSMCs and attenuates AAA formation, which is possibly attributed to the secretome of browning adipocytes., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objectives: Spinocerebellar ataxia type 3 is a disorder within the brain network. However, the relationship between the brain network and disease severity is still unclear. This study aims to investigate changes in the white matter (WM) structural motor network, both in preclinical and ataxic stages, and its relationship with disease severity., Methods: For this study, 20 ataxic, 20 preclinical SCA3 patients, and 20 healthy controls were recruited and received MRI scans. Disease severity was quantified using the SARA and ICARS scores. The WM motor structural network was created using probabilistic fiber tracking and was analyzed using graph theory and network-based statistics at global, nodal, and edge levels. In addition, the correlations between network topological measures and disease duration or clinical scores were analyzed., Results: Preclinical patients showed increasing assortativity of the motor network, altered subnetwork including 12 edges of 11 nodes, and 5 brain regions presenting reduced nodal strength. In ataxic patients assortativity of the motor network also increased, but global efficiency, global strength, and transitivity decreased. Ataxic patients showed a wider altered subnetwork and a higher number of reduced nodal strengths. A negative correlation between the transitivity of the motor network and SARA and ICARS scores was observed in ataxic patients., Interpretation: Changes to the WM motor network in SCA3 start before ataxia onset, and WM motor network involvement increases with disease progression. Global network topological measures of the WM motor network appear to be a promising image biomarker for disease severity. This study provides new insights into the pathophysiology of disease in SCA3/MJD., (© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

RNA C-to-U editing in organelles is essential for plant growth and development; however, the underlying mechanism is not fully understood. Here, we report that pentatricopeptide repeat (PPR)-E subclass proteins carry out RNA C-to-U editing by recruiting the trans deaminase PPR motifs, coiled-coil, and DYW domain-containing protein 1 (PCW1) in maize (Zea mays) mitochondria. Loss-of-function of bZIP and coiled-coil domain-containing PPR 1 (bCCP1) or PCW1 arrests seed development in maize. bCCP1 encodes a bZIP and coiled-coil domain-containing PPR protein, and PCW1 encodes an atypical PPR-DYW protein. bCCP1 is required for editing at 66 sites in mitochondria and PCW1 is required for editing at 102 sites, including the 66 sites that require bCCP1. The PCW1-mediated editing sites are exclusively associated with PPR-E proteins. bCCP1 interacts with PCW1 and the PPR-E protein Empty pericarp7 (EMP7). Two multiple organellar RNA editing factor (MORF) proteins, ZmMORF1 and ZmMORF8, interact with PCW1, EMP7, and bCCP1. ZmMORF8 enhanced the EMP7-PCW1 interaction in a yeast three-hybrid assay. C-to-U editing at the ccmFN-1553 site in maize required EMP7, bCCP1, and PCW1. These results suggest that PPR-E proteins function in RNA editing by recruiting the trans deaminase PCW1 and bCCP1, and MORF1/8 assist this recruitment through protein-protein interactions., (© American Society of Plant Biologists 2022. All rights reserved. For permissions, please email: journals.permissions@oup.com.)