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Background: The current method for liver graft implantation during the anhepatic phase is complex. Therefore, this study aimed to introduce a modified orthotopic liver transplantation (OLT) technique with major vascular reconstruction using cuff technique to simplify the process of liver graft implantation during the anhepatic phase., Methods: Twenty-four canines were randomly assigned to two groups: the modified orthotopic liver transplantation group (M-OLT, n  = 12) and the control group (n = 12). All animals were randomly assigned to the donor or recipient groups. The recipients received orthotopic liver transplantation using a modified technique in the M-OLT group, and OLT using traditional implantation technique without venovenous bypass was performed in the control group. The donor and recipient characteristics were compared between the two groups. Vascular anastomotic patency was evaluated using angiography immediately and one week after surgery., Results: All recipients underwent successful liver transplantation. There were no significant differences between the two groups in terms of sex, body weight, or cold ischemia time of the donor liver. However, recipients in the M-OLT group had a shorter operation time, less intraoperative blood loss, shorter anhepatic phase, shorter vascular occlusion time, and shorter warm ischemia time than that in the control group (all p  < 0.05). No anastomotic leakage or stenosis was detected in either group after liver transplantation. One recipient in the M-OLT group and three in the control group died within one week of transplantation., Conclusions: This modified technique is safe and feasible for canine liver transplantation and can significantly simplify liver graft implantation procedures during the anhepatic period., Competing Interests: No authors have conflicts of interest or financial ties to disclose., (© 2024 The Authors. Published by Elsevier Inc.)

Although stroke is a frequent cause of permanent disability, our ability to promote stroke recovery is limited. Here, we design a small-molecule stroke recovery promoting agent that works by dissociating γ-aminobutyric acid (GABA) transporter 1 (GAT-1) from syntaxin1A (Synt1A), a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein. Stroke induces an increase in GAT-1-Synt1A interaction in the subacute phase, a critical period for functional recovery. Uncoupling GAT-1-Synt1A reverses stroke-induced GAT-1 dysfunction and cortical excitability decline and enhances synaptic GABAergic inhibition and consequently cortical oscillations and network plasticity by facilitating the assembly of the SNARE complex at the synapse. Based on the molecular mechanism of GAT-1 binding to Synt1A, we design GAT-1-Synt1A blockers. Among them, ZLQ-3 exhibits the greatest potency. Intranasal use of ZLQ-3-1, a glycosylation product of ZLQ-3, substantially lessens impairments of sensorimotor and cognitive functions in rodent models. This compound, or its analogs, may serve as a promoting agent for stroke recovery., Competing Interests: Declaration of interests D.-Y.Z., Y.-H.L., Y.-J.Q., and T.-Y.L. are inventors on the following PCT on ZLQ series compounds application: filed on 15/08/2024, application no. PCT/CN2024/112442. Y.-H.L., Y.-J.Q., and T.-Y.L. are inventors on the following Chinese patent on ZLQ series compounds application: publication no. CN117384253A., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Chemotherapy resistance is still a great challenge for clinical treatment of lung cancer. Here, we found that doxorubicin (DOX) induced an increase of labile Zn 2+ in lung cancer cells, and these labile Zn 2+ protected tumor cells against DOX cytotoxicity. Nanoparticles encapsulating N,N,N',N'-Tetrakis (2-pyridylmethyl)-ethylenediamine (TPEN) were then constructed to chelate labile Zn 2+ for tumor therapy. Application of nanoparticle-encapsulated TPEN at low dose not only avoided severe side effects caused by removing physiological Zn 2+ but also effectively chelated drug-induced labile Zn 2+ , and thereby enhanced DOX cytotoxicity. Mechanistically, nanosized TPEN inhibits ABCB1-mediated drug export potentiated by drug-induced labile Zn 2+ . Finally, the results unraveled that nanosized TPEN at low dose endowed DOX with the killing ability on resistant tumor cells. Taken together, our results demonstrate that chelating drug-induced labile Zn 2+ by nanosized TPEN at low dose enhances lung cancer chemotherapy by inhibiting ABCB1, providing a feasible strategy to overcome chemoresistance in lung cancer., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

As a prevalent spine disorder, Lumbar disc herniation (LDH) has been affecting more than 2 % of the worldwide population and is characterised by uncertain causes and recurring episodes. Studying the brain activity of patients could potentially provide insights into its pathogenesis and significantly enhance therapy. Therefore, we here examined brain function in patients under Spinal Manipulative Therapy (SMT). By analysing regional homogeneity (ReHo) at different frequency bands, we identified the discrepancies in brain activity between LDH patients and healthy people, highlighting the frequency dependence of spontaneous low-frequency oscillations among patients with LDH. Choosing seeds based on the peak ReHo differences helped to elucidate the functional connectivity alterations in the brain regions of LDH. Overall, this study showed that SMT significantly reduced pain, improved dysfunction, and partially rectified aberrant local consistency and functional connection in patients with LDH, not only offering insights into the pathophysiology of LDH from a neurological standpoint, but also providing inspiration for the development of new therapies based on neurobiology., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Honggen Du reports financial support was provided by the 10.13039/501100001809National Natural Science Foundation of China. Ya Wen reports financial support was provided by Zhejiang Provincial Traditional Chinese Medicine Science and Technology Plan Project. Ya Wen reports financial support was provided by 10.13039/501100004731Natural Science Foundation of Zhejiang Province. Xin Jin reports financial support was provided by 10.13039/501100004731Natural Science Foundation of Zhejiang Province. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Immunosuppressive tumor-associated macrophages (TAMs) account for a high proportion of the tumor tissue and significantly impede immunoefficacy. Furthermore, the signal regulatory protein α (SIRPα) expressed in TAMs adversely correlates with macrophage activation and phagocytosis, resulting in immunosurveillance escape. To address these difficulties, a mannose-modified, pH-responsive nanoplatform with resiquimod (R848) and 2', 3'-cyclic GMP-AMP (cGAMP) co-encapsulation (named M-PNP@R@C) is designed to polarize TAMs and lower SIRPα expression. The co-delivery of R848 and cGAMP synergistically facilitates the polarization of TAMs from the anti-inflammatory M2 phenotype into the pro-inflammatory M1 phenotype, thereby enhancing antitumor immunotherapy. Remarkably, activation of the cGAMP-mediated stimulator of interferon genes (STING) in TAMs significantly downregulates the expression of SIRPα, which synergizes with the cluster of differentiation 47 (CD47) antibody for the dual blockade of the CD47-SIRPα axis. Further analysis of single-cell RNA sequencing indicates that STING activation downregulates SIRPα by regulating intracellular fatty acid oxidation metabolism. In vivo studies indicate that M-PNP@R@C significantly inhibits tumor growth with a potent antitumor immune response in melanoma graft tumor models. After synergy with anti-CD47, the double blockade strategies of the SIRPα/CD47 axis result in a notable inhibition of lung metastasis. A prolonged survival rate is observed after combination treatment with CD47 and programmed death ligand-1 antibodies for the triple immune checkpoint blockade. In summary, our study provides original insights into the potential role of the STING pathway in macrophage-based immunotherapy, thus offering a potential combinatorial strategy for cancer therapy., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier B.V.)

Strain SYSU D00308 T , a short-rod-shaped bacterium, was isolated from a sandy soil collected from the Gurbantunggut Desert, Xinjiang, PR China. Strain SYSU D00308 T was Gram-stain-negative, aerobic, pink-pigmented, non-motile, catalase- and oxidase-positive. The strain grew at 4-37 ℃, pH 5.0-8.0 and 0-1.5% (w/v) NaCl. 16S rRNA gene sequencing analyses demonstrated that strain SYSU D00308 T belonged to the genus Rufibacter and exhibited the highest sequence similarity (97.4%) to Rufibacter glacialis MDT1-10-3 T . Summed features 3, 4, and iso-C 15:0 were the major fatty acids, and menaquinone 7 (MK-7) was the sole respiratory menaquinone. The polar lipid profiles comprised phosphatidylethanolamine, an unidentified glycolipid, an unidentified phospholipid, two unidentified aminophospholipids, and two unidentified lipids. The genome size and DNA G + C content of strain SYSU D00308 T were 5,176,683 bp and 54.8%, respectively. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between SYSU D00308 T and members of the genus Rufibacter were 77.7-81.8% and 20.4-23.4% respectively, which were less than the corresponding thresholds (ANI: 95-96%; dDDH: 70%) for prokaryotic species definition. According to the genotypic, phenotypic and phylogenetic characteristics, strain SYSU D00308 T represents a novel species of the genus Rufibacter. We propose the name, Rufibacter psychrotolerans sp. nov., with SYSU D00308 T (= CGMCC 1.18621 T = KCTC 82275 T = MCCC 1K04970 T ) as the type strain., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A novel rod-shaped bacterium, designated as strain SYSU D60015 T that formed yellowish colonies was isolated from a sandy soil collected from the Kumtag Desert in Xinjiang, China. Cells were Gram-stain-negative, oxidase-positive, catalase-negative and motile with a single polar flagellum. Growth optimum occurred between 28 and 37 °C, pH 7.0 and with 0-0.5% (W/V) NaCl. The predominant cellular fatty acids (> 5%) were summed feature 8 (C 18:1 ω7c and/or C 18:1 ω6c), C 19:0 cyclo ω8c, C 18:1 ω7c 11-methyl and C 16:0 . The polar lipid profile contained one phosphatidylethanolamine, one diphosphatidylglycerol, one phosphatidylglycerol, one unidentified phospholipid, three unidentified aminolipids, two unidentified aminophospholipids and seven unidentified lipids. The only respiratory quinone was ubiquinone-10. Based on 16S rRNA gene sequence phylogenetic analysis, strain SYSU D60015 T was found to form a distinct linage within the family Sneathiellaceae, and had 16S rRNA gene sequence similarities of 90.8% to Taonella mepensis H1 T , and 90.2% to Ferrovibrio denitrificans S3 T . The genome of SYSU D60015 T was 5.66 Mb in size with 68.2% of DNA G + C content. The low digital DNA-DNA hybridization (dDDH, 18.0%), average nucleotide identity (ANI, 77.5%) and amino acid identity (AAI, 56.0%) values between SYSU D60015 T and Ferrovibrio terrae K5 T indicated that SYSU D60015 T might represent a distinct genus. Based on the phylogenetic, phenotypic, chemotaxonomic and genomic data, we propose Desertibaculum subflavum gen. nov., sp. nov. as a novel species of a new genus within the family Sneathiellaceae. The type strain is SYSU D60015 T (= NBRC 112952 T  = CGMCC 1.16256 T )., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

A series of amino acid ester trifluoroacetate derivatives was synthesized from scaberol C. They were screened for their inhibitory activity against Non-Small Cell Lung Cancer (NSCLC) cells. Among them, compound 2 l showed significant cytotoxicity against A549 and H460 cells (IC 50 ), and was more active than cisplatin (DDP). The epidermal growth factor receptor (EGFR) was overexpressed in NSCLC, which was the target of multiple cancer therapies and a strong prognostic indicator. Our previous studies reported that the target of scaberol C derivatives against NSCLC cells was EGFR. And then molecular docking analysis and molecular dynamics (MD) simulations indicated that 2 l can stably and covalently bind to the EGFR target protein.

An aerobic, Gram-stain-negative bacterium, designated as SYSU D00382 T , was sourced from soil of Gurbantunggut Desert, PR China. The strain was short-rod-shaped, oxidase-positive and catalase-negative, with yellow-colored, convex, round, and smooth colonies on TSA plate. Growth and proliferation occurred at 4-37 °C (optimal: 28-30 °C), pH 5.0-8.0 (optimal: pH 6.0-7.0) and NaCl concentration of 0-2.5% (optimal: 0-0.5%). The 16S rRNA gene based phylogenetic assessment showed that SYSU D00382 T belonged to the genus Pedobacter, and was most closely related to Pedobacter ginsengisoli Gsoil 104 T with similarity of 97.7%. The genomic DNA G+C content of SYSU D00382 T was 46.4%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between SYSU D00382 T and P. ginsengisoli Gsoil 104 T were 75.7% and 17.5%, respectively. The main polar lipid was phosphatidylethanolamine. The major fatty acids (> 5%) were iso-C 15:0 , iso-C 17:0 3-OH, summed features 3 and 9. The sole respiratory quinone identified was MK-7. The phylogeny based on 16S rRNA gene and whole-genome sequences revealed that SYSU D00382 T formed a robust lineage with P. ginsengisoli Gsoil 104 T . Based on phenotypic, phylogenetic and genotypic data, a novel specie named Pedobacter deserti sp. nov. is proposed. The type strain is SYSU D00382 T (= CGMCC 1.18627 T  = MCCC 1K04972 T  = KCTC 82279 T )., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Aims: Vitamin D deficiency (VDD) is prevalent in the population, with inadequate intake, impaired absorption and metabolism as the main causative factors. VDD increases the risk of developing chronic diseases such as type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), but the molecular mechanisms underlying this phenomenon are not known. The aim of this study was to investigate the association and potential mechanisms of vitamin D levels with the progression of DN by analyzing general clinical data and using bioinformatics methods., Methods: The study included 567 diabetes mellitus type 2 (T2DM) patients from the Rocket Force Characteristic Medical Center as the case group and 221 healthy examinees as the normal control group. T2DM patients were categorized into T2DM, early diabetic nephropathy (EDN), and advanced diabetic nephropathy (ADN) based on the progression of diabetic nephropathy. The renal RNA-seq and scRNA-seq data of patients with DN were mined from public databases, and the differential expression of vitamin D-related genes in normal-EDN-ADN was analyzed by bioinformatics method, protein interaction network was constructed, immune infiltration was evaluated, single cell map was drawn, and potential mechanisms of VD and DN interaction were explored., Results: Chi-square test showed that vitamin D level was significantly negatively correlated with DN progression ( p  < 0.001). Bioinformatics showed that the expression of vitamin D-related cytochrome P450 family genes was down-regulated, and TLR4 and other related inflammatory genes were abnormally up-regulated with the progression of DN. Vitamin D metabolism disturbance up-regulate "Nf-Kappa B signaling pathway," B cell receptor signaling pathway and other immune regulation and insulin resistance related pathways, and inhibit a variety of metabolic pathways. In addition, vitamin D metabolism disturbance are strongly associated with the development of diabetic cardiomyopathy and several neurological disease complications., Conclusion: VDD or vitamin D metabolism disturbance is positively associated with the severity of renal injury. The mechanisms may involve abnormal regulation of the immune system by vitamin D metabolism disturbance, metabolic suppression, upregulation of insulin resistance and inflammatory signalling pathways., 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 Gao, Song, Ou, Cheng, Zhang, Liu, Dong and Wang.)

This study aimed to evaluate the effectiveness of the endometrial receptivity array (ERA), endometrial immune profiling, and a combination of both in improving the pregnancy outcomes for multiple implantation failure patients. According to patients' willingness, 1429 women who incurred at least two or more consecutive implantation failures in IVF/ICSI treatment opted for frozen embryo transfer and were divided into four groups: 'No test', 'Immune Profiling', 'ERA' and 'ERA+ Immune Profiling'. Women in three test groups underwent timed endometrial biopsy for ERA, immune profiling, a combination of both. We observed the overall incidence rates of the displaced window of implantation (WOI) and endometrial immune dysregulation were 75.14% and 79.29%, respectively. After 1:1 propensity score matching (PSM), our data revealed that the 'ERA' and 'ERA + Immune Profiling' groups demonstrated significantly higher rates of biochemical, clinical, ongoing pregnancy, and implantation compared to the 'No test' group (p < 0.01). The 'Immune Profiling' group showed a higher implantation rate compared to 'No test' group (p < 0.05). Furthermore, when comparing three test groups, the 'ERA + Immune Profiling' group exhibited notably higher rates of clinical and ongoing pregnancy compared to the 'Immune Profiling' group (p < 0.017). However, there was no association between endometrial immune profiling and ERA phases, and their results did not differ between embryo implantation and non-implantation in these patients. Our findings underline the increased implantation rates by use of ERA and endometrial immune profiling in patients with multiple implantation failure, either individually or corporately. Moreover, a combination of both could improve their pregnancy outcomes significantly., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Efferocytosis is a crucial process whereby phagocytes engulf and eliminate apoptotic cells (ACs). This intricate process can be categorized into four steps: (1) ACs release "find me" signals to attract phagocytes, (2) phagocytosis is directed by "eat me" signals emitted by ACs, (3) phagocytes engulf and internalize ACs, and (4) degradation of ACs occurs. Maintaining immune homeostasis heavily relies on the efficient clearance of ACs, which eliminates self-antigens and facilitates the generation of anti-inflammatory and immunosuppressive signals that maintain immune tolerance. However, any disruptions occurring at any of the efferocytosis steps during apoptosis can lead to a diminished efficacy in removing apoptotic cells. Factors contributing to this inefficiency encompass dysregulation in the release and recognition of "find me" or "eat me" signals, defects in phagocyte surface receptors, bridging molecules, and other signaling pathways. The inadequate clearance of ACs can result in their rupture and subsequent release of self-antigens, thereby promoting immune responses and precipitating the onset of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. A comprehensive understanding of the efferocytosis process and its implications can provide valuable insights for developing novel therapeutic strategies that target this process to prevent or treat autoimmune diseases., 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.)

Elongation of very long-chain fatty acids protein 6 (ELOVL6) plays a pivotal role in the synthesis of endogenous fatty acids, influencing energy balance and metabolic diseases. The primary objective of this study was to discover the molecular attributes and regulatory roles of ELOVL6 in male Nile tilapia, Oreochromis niloticus. The full-length cDNA of elovl6 was cloned from male Nile tilapia, and was determined to be 2255-bp long, including a 5'-untranslated region of 193 bp, a 3'-untranslated region of 1252 bp, and an open reading frame of 810 bp encoding 269 amino acids. The putative protein had typical features of ELOVL proteins. The transcript levels of elovl6 differed among various tissues and among fish fed with different dietary lipid sources. Knockdown of elovl6 in Nile tilapia using antisense RNA technology resulted in significant alterations in hepatic morphology, long-chain fatty acid synthesis, and fatty acid oxidation, and led to increased fat deposition in the liver and disrupted glucose/lipid metabolism. A comparative transcriptomic analysis (elovl6 knockdown vs. the negative control) identified 5877 differentially expressed genes with significant involvement in key signaling pathways including the peroxisome proliferator-activated receptor signaling pathway, fatty acid degradation, glycolysis/gluconeogenesis, and the insulin signaling pathway, all of which are crucial for lipid and glucose metabolism. qRT-PCR analyses verified the transcript levels of 13 differentially expressed genes within these pathways. Our findings indicate that elovl6 knockdown in male tilapia impedes oleic acid synthesis, culminating in aberrant nutrient metabolism., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Disturbance in mitochondrial homeostasis within proximal tubules is a critical characteristic associated with diabetic kidney disease (DKD). CaMKKβ/AMPK signaling plays an important role in regulating mitochondrial homeostasis. Despite the downregulation of CaMKKβ in DKD pathology, the underlying mechanism remains elusive. The expression of NEDD4L, which is primarily localized to renal proximal tubules, is significantly upregulated in the renal tubules of mice with DKD. Coimmunoprecipitation (Co-IP) assays revealed a physical interaction between NEDD4L and CaMKKβ. Moreover, deletion of NEDD4L under high glucose conditions prevented rapid CaMKKβ protein degradation. In vitro studies revealed that the aberrant expression of NEDD4L negatively influences the protein stability of CaMKKβ. This study also explored the role of NEDD4L in DKD by using AAV-shNedd4L in db/db mice. These findings confirmed that NEDD4L inhibition leads to a decrease in urine protein excretion, tubulointerstitial fibrosis, and oxidative stress, and mitochondrial dysfunction. Further in vitro studies demonstrated that si-Nedd4L suppressed mitochondrial fission and reactive oxygen species (ROS) production, effects antagonized by si-CaMKKβ. In summary, the findings provided herein provide strong evidence that dysregulated NEDD4L disturbs mitochondrial homeostasis by negatively modulating CaMKKβ in the context of DKD. This evidence underscores the potential of therapeutic interventions targeting NEDD4L and CaMKKβ to safeguard renal tubular function in the management of DKD., (© 2024. The Author(s).)

Oxygen vacancies (OVs) have garnered significant interest for their role as active sites, enhancing the catalytic efficiency of various catalysts. Despite their widespread application in environmental purification processes, the generation of OVs conventionally depends on high-temperature conditions and strong reducing agents for the extraction of surface partial oxygen atoms from catalysts. In this work, bismuth oxybromide (BiOBr) nanosheets with varying levels of OVs were synthesized via a simple and effective solvothermal method. This novel method affords precise control over the conduction band (CB) and valence band (VB) positions of BiOBr. The presence of different OVs exhibited varying photocatalytic efficiencies in the degradation of bisphenol A (BPA) under visible light irradiation, with higher levels of OVs resulting in superior photocatalytic performance. Furthermore, radical scavenger experiments demonstrated that superoxide oxides (O 2 •- ) and holes (h + ) were the primary reactive oxygen species for BPA degradation. Additionally, BiOBr-OVs exhibited excellent anti-interference and stability in water matrices containing diverse inorganic anions and organic compounds. This work provides a simple and effective approach for the fine-regulating of catalysts through interfacial defect engineering, paving the way for their practical application in environmental decontamination., 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.)

Objective: To investigate predictors of anticoagulation efficacy in deep venous thrombosis (DVT) by ultrasound elastography (UE)., Methods: The basic clinical, laboratory and ultrasound treatment data of fifty-eight patients with DVT were collected and analyzed. Then the results of ultrasound after 3-month anticoagulation treatment were compared among different groups. Multiple logistic regression analysis was used to identify independent risk factors that affected anticoagulation efficacy. The predictive efficacy of each independent risk factor was accessed by drawing operating characteristic (ROC) curves., Results: According to the regression analysis, the elastic modulus (OR = 0.631, P = 0.001) and strain rate ratio (OR = 0.332, P = 0.006) were identified as independent risk factors for the effectiveness of anticoagulation therapy in patients with DVT. According to the ROC curves, elastic modulus and strain rate ratio could predict effective anticoagulation therapy for DVT, and the optimal threshold values were 22.10 kPa and 1.80 respectively. The corresponding AUC values were 0.879 and 0.854, with a sensitivity of 71.4% and 59.5%, a specificity of 93.7%, and a Youden index of 65.1% and 62.7%, respectively., Conclusions: The elastic modulus (≤22.10 kPa) or strain rate ratio (≤1.80) of the thrombus were independent predictors for the effectiveness of anticoagulation therapy.

NK cells play a role in various cancers, but their role in head and neck squamous cell carcinoma (HNSCC) still needs to be explored. All public data are obtained from the Cancer Genome Atlas Program (TCGA) database. All analysis was performed using specific packages in R software. In our study, we quantified the immune microenvironment of HNSCC through multiple algorithms. Next, we identified NK cell-associated genes by quantifying NK cells, including SSNA1, TRIR, PAXX, DPP7, WDR34, EZR, PHLDA1 and ELOVL1. Then, we explored the single-cell expression pattern of these genes in the HNSCC microenvironment. Univariate Cox regression analysis indicated that the EZR, PHLDA1 and ELOVL1 were related to the prognosis of HNSCC patients. Following this, we selected EZR for further analysis. Our results showed that the patients with high EZR expression might have a poor prognosis and worse clinical features. Biological enrichment analysis showed that EZR is associated with many oncogenic pathways and a higher tumour stemness index. Meanwhile, we found that EZR can remodel the immune microenvironment of HNSCC. Moreover, we noticed that EZR could affect the immunotherapy and specific drug sensitivity, making it an underlying clinical target. In summary, our results can improve the understanding of NK cell in HNSCC. Meanwhile, we identified EZR as the underlying clinical target of HNSCC., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The recombinant genotypes that can be produced when closely related species mate improve the genetic diversity of the population. Among closely related species, the link between interspecific reproduction behaviors and genetic diversity has barely been studied. Reticulitermes chinensis and R. flaviceps, which live close to each other, were used as research subjects in our study to find out how preferring conspecifics affects reproductive behavior between species. We discovered that neither R. chinensis nor R. flaviceps displayed preference behavior for conspecifics. Males of R. chinensis and R. flaviceps chased and groomed not only intraspecific females but also interspecific females. In a brief period of time, 2 mating behaviors, intra- and interspecific mating, were also observed. There were no significant differences in the duration of each behavior (tandem, grooming, and mating) between interspecies and intraspecies partners. Moreover, genetic analysis showed both interspecific mating and intraspecific mating can produce living offspring when the 2 types of mating occur in a colony. Our findings showed that there was no obvious intraspecific preference between the 2 species of termite Reticulitermes when it came to tandem, grooming, and mating, which not only makes it easier for interspecific hybridization to occur but also sheds light on the genetic diversity., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America.)

Background: The purpose of this study was to explore the value of the left internal mammary artery flow velocity (LIMAV) measured by ultrasound before coronary artery bypass grafting (CABG) in predicting the prognosis of patients after left internal mammary artery (LIMA) bypass grafting., Methods: One hundred and four patients who underwent CABG with LIMA as the bridge vessel in the cardiovascular surgery department of our hospital between May 2018 and June 2019 were selected. All patients underwent transthoracic Doppler ultrasonography to measure LIMAV preoperatively. Intraoperatively, mean graft flow (MGF) and pulsatility index (PI) of the LIMA bridge were measured using transit time flow measurement (TTFM). The primary endpoint event in this study was cardiac death within 18 months after surgery., Results: The Cox survival analysis showed that the MGF, the LIMAV and left ventricular ejection fraction (LVEF) were risk factors for death after CABG. The cut-offs of MGF, LIMAV and LVEF for the prediction of death after CABG were ≤ 14 mL/min (area under the curve (AUC): 0.830; sensitivity: 100%; specificity: 65.6%), ≤ 60 cm/s (AUC: 0.759; sensitivity: 65.5%; specificity: 85.3%), and ≤ 44% (AUC: 0.724; sensitivity: 50%; specificity: 88.5%), respectively. Compared with the use of MGF, MGF + LIMAV, combination of the MGF + LIMAV + LVEF (AUC: 0.929; sensitivity: 100%; specificity: 81.1%) resulted in a stronger predictive value (MGF vs. MGF + LIMAV + LVEF: P = 0.02)., Conclusion: LIMAV measured by preoperative transthoracic ultrasound combined with intraoperative MGF and LVEF may have a greater value in predicting patients' risk of cardiac death after CABG., Competing Interests: The authors declare that they have no conflict of interest., (Copyright 2023, Guo et al.)

Deserts occupy one-third of the Earth's terrestrial surface and represent a potentially significant reservoir of microbial biodiversity, yet the majority of desert microorganisms remain uncharacterized and are seen as "microbial dark matter". Here, we introduce a multi-omics strategy, culturomics-based metagenomics (CBM) that integrates large-scale cultivation, full-length 16S rRNA gene amplicon, and shotgun metagenomic sequencing. The results showed that CBM captured a significant amount of taxonomic and functional diversity missed in direct sequencing by increasing the recovery of amplicon sequence variants (ASVs) and high/medium-quality metagenome-assembled genomes (MAGs). Importantly, CBM allowed the post hoc recovery of microbes of interest (e.g., novel or specific taxa), even those with extremely low abundance in the culture. Furthermore, strain-level analyses based on CBM and direct sequencing revealed that the desert soils harbored a considerable number of novel bacterial candidates (1941, 51.4%), of which 1095 (from CBM) were culturable. However, CBM would not exactly reflect the relative abundance of true microbial composition and functional pathways in the in situ environment, and its use coupled with direct metagenomic sequencing could provide greater insight into desert microbiomes. Overall, this study exemplifies the CBM strategy with high-resolution is an ideal way to deeply explore the untapped novel bacterial resources in desert soils, and substantially expands our knowledge on the microbial dark matter hidden in the vast expanse of deserts., (© 2023. Springer Nature Limited.)

Stroke is the leading cause of death and long-term disability worldwide. But treatments are not available to promote functional recovery, and efficient therapies need to be investigated. Stem cell-based therapies hold great promise as potential technologies to restore function in brain disorders. Loss of GABAergic interneurons after stroke may result in sensorimotor defects. Here, by transplanting human brain organoids resembling the MGE domain (human MGE organoids, hMGEOs) derived from human induced pluripotent stem cells (hiPSCs) into the infarcted cortex of stroke mice, we found that grafted hMGEOs survived well and primarily differentiated into GABAergic interneurons and significantly restored the sensorimotor deficits of stroke mice for a long time. Our study offers the feasibility of stem cell replacement therapeutics strategy for stroke., 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 Inc. All rights reserved.)

Drug resistance causes catastrophic cancer treatment failures. Mutations in target proteins with altered drug binding indicate a main mechanism of cancer drug resistance (CDR). Global research has generated considerable CDR-related data and well-established knowledge bases and predictive tools. Unfortunately, these resources are fragmented and underutilized. Here, we examine computational resources for exploring CDR caused by target mutations, analyzing these tools based on their functional characteristics, data capacity, data sources, methodologies and performance. We also discuss their disadvantages and provide examples of how potential inhibitors of CDR have been discovered using these resources. This toolkit is designed to help specialists explore resistance occurrence effectively and to explain resistance prediction to non-specialists easily., 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.)

In the central nervous system, nitric oxide (NO), a free gas with multitudinous bioactivities, is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase (nNOS). In the past 20 years, the studies in our group and other laboratories have suggested a significant involvement of nNOS in a variety of neurological and neuropsychiatric disorders. In particular, the interactions between the PDZ domain of nNOS and its adaptor proteins, including post-synaptic density 95, the carboxy-terminal PDZ ligand of nNOS, and the serotonin transporter, significantly influence the subcellular localization and functions of nNOS in the brain. The nNOS-mediated protein-protein interactions provide new attractive targets and guide the discovery of therapeutic drugs for neurological and neuropsychiatric disorders. Here, we summarize the work on the roles of nNOS and its association with multiple adaptor proteins on neurological and neuropsychiatric disorders., (© 2023. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Background: N7-methylguanosine (m7G) is one of the most common RNA posttranscriptional modifications; however, its potential role in hepatocellular carcinoma (HCC) remains unknown. We developed a prediction signature based on m7G-related long noncoding RNAs (lncRNAs) to predict HCC prognosis and provide a reference for immunotherapy and chemotherapy., Methods: RNA-seq data from The Cancer Genome Atlas (TCGA) database and relevant clinical data were used. Univariate and multivariate Cox regression analyses were conducted to identify m7G-related lncRNAs with prognostic value to build a predictive signature. We evaluated the prognostic value and clinical relevance of this signature and explored the correlation between the predictive signature and the chemotherapy treatment response of HCC. Moreover, an in vitro study to validate the function of CASC19 was performed., Results: Six m7G-related lncRNAs were identified to create a signature. This signature was considered an independent risk factor for the prognosis of patients with HCC. TIDE analyses showed that the high-risk group might be more sensitive to immunotherapy. ssGSEA indicated that the predictive signature was strongly related to the immune activities of HCC. HCC in high-risk patients was more sensitive to the common chemotherapy drugs bleomycin, doxorubicin, gemcitabine, and lenalidomide. In vitro knockdown of CASC19 inhibited the proliferation, migration and invasion of HCC cells., Conclusion: We established a 6 m7G-related lncRNA signature that may assist in predicting the prognosis and response to chemotherapy and immunotherapy of HCC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Peng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The basolateral amygdala (BLA) neurons are primarily glutamatergic and have been associated with emotion regulation. However, little is known about the roles of BLA neurons expressing neuronal nitric oxide synthase (nNOS, Nos1) in the regulation of emotional behaviors., Methods: Using Nos1 - cre mice and chemogenetic and optogenetic manipulations, we specifically silenced or activated Nos1 + or Nos1 - neurons in the BLA, or silenced their projections to the anterdorsal bed nucleus of the stria terminalis (adBNST) and ventral hippocampus (vHPC). We measured anxiety behaviors in elevated plus maze (EPM) and open-field test (OFT), and measured depression behaviors in forced swimming test (FST) and tail suspension test (TST)., Results: BLA Nos1 + neurons were predominantly glutamatergic, and glutamatergic but not GABAergic Nos1 + neurons were involved in controlling anxiety- and depression-related behaviors. Interestingly, by selectively manipulating the activities of BLA Nos1 + and Nos1 - excitatory neurons, we found that they had opposing effects on anxiety- and depression-related behaviors. BLA Nos1 + excitatory neurons projected to the adBNST, this BLA-adBNST circuit controlled the expression of anxiety- and depression-related behaviors, while BLA Nos1 - excitatory neurons projected to vHPC, this BLA-vHPC circuit contributed to the expression of anxiety- and depression-related behaviors. Moreover, excitatory vHPC-adBNST circuit antagonized the role of BLA-adBNST circuit in regulating anxiety- and depression-related behaviors., Conclusions: BLA Nos1 + and Nos1 - excitatory neuron subpopulations exert different effects on anxiety- and depression-related behaviors through distinct projection circuits, providing a new insight of BLA excitatory neurons in emotional regulation., Limitations: We did not perform retrograde labeling from adBNST and vHPC regions., Competing Interests: Conflict of interest All the authors declare no competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aristolochic acid I (AAI) is a well established nephrotoxin and human carcinogen. Cytosolic NAD(P)H quinone oxidoreductase 1 (NQO1) plays an important role in the nitro reduction of aristolochic acids, leading to production of aristoloactam and AA-DNA adduct. Application of a potent NQO1 inhibitor dicoumarol is limited by its life-threatening side effect as an anticoagulant and the subsequent hemorrhagic complications. As traditional medicines containing AAI remain available in the market, novel NQO1 inhibitors are urgently needed to attenuate the toxicity of AAI exposure. In this study, we employed comprehensive 2D NQO1 biochromatography to screen candidate compounds that could bind with NQO1 protein. Four compounds, i.e., skullcapflavone II (SFII), oroxylin A, wogonin and tectochrysin were screened out from Scutellaria baicalensis. Among them, SFII was the most promising NQO1 inhibitor with a binding affinity (K D  = 4.198 μmol/L) and inhibitory activity (IC 50  = 2.87 μmol/L). In human normal liver cell line (L02) and human renal proximal tubular epithelial cell line (HK-2), SFII significantly alleviated AAI-induced DNA damage and apoptosis. In adult mice, oral administration of SFII dose-dependently ameliorated AAI-induced renal fibrosis and dysfunction. In infant mice, oral administration of SFII suppressed AAI-induced hepatocellular carcinoma initiation. Moreover, administration of SFII did not affect the coagulation function in short term in adult mice. In conclusion, SFII has been identified as a novel NQO1 inhibitor that might impede the risk of AAI to kidney and liver without obvious side effect., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

With the construction and operation of railways in cold regions, the asymmetric deformation of subgrades due to the difference in the transverse ground temperature has become a prominent issue. A comprehensive evaluation of the transverse ground temperature difference and investigation of the corresponding mitigation measures should be conducted to avoid or minimize the damage resulting from this difference, thereby improving subgrade stability and reducing deformation. In this study, the time history variations in the homogeneity and symmetry indices of the ground temperature at typical instances that reflect the spatial and temporal changes in the temperature difference of the subgrade were proposed as evaluation indices. The feasibility of these evaluation indices was verified through numerical models with different types of anti-frost berms. Subsequently, the numerical models were used to analyze the ground temperature evaluation indices of a subgrade with expanded polystyrene (EPS) insulation board and polyurethane (PU) insulation board at different locations. Additionally, the performances of each mitigation measure in eliminating or reducing the ground temperature difference were assessed and compared. The results show that all the mitigation measures could improve the homogeneity and symmetry of the ground temperature distribution. The maximum mitigation rates for the homogeneity and symmetry are 97.87% and 45.90%, respectively. This study provides a comprehensive evaluation method for the temperature difference of subgrades constructed in cold regions and a theoretical reference for the selection of anti-frost measures in the design, operation, and maintenance of subgrades in cold regions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Increasing evidence suggests that immune modulation contributes to the pathogenesis and progression of diabetic nephropathy (DN). However, the role of immune modulation in DN has not been elucidated. The purpose of this study was to search for potential immune-related therapeutic targets and molecular mechanisms of DN., Methods: Gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. A total of 1793 immune-related genes were acquired from the Immunology Database and Analysis Portal (ImmPort). Weighted gene co-expression network analysis (WGCNA) was performed for GSE142025, and the red and turquoise co-expression modules were found to be key for DN progression. We utilized four machine learning algorithms, namely, random forest (RF), support vector machine (SVM), adaptive boosting (AdaBoost), and k-nearest neighbor (KNN), to evaluate the diagnostic value of hub genes. Immune infiltration patterns were analyzed using the CIBERSORT algorithm, and the correlation between immune cell type abundance and hub gene expression was also investigated., Results: A total of 77 immune-related genes of advanced DN were selected for subsequent analyzes. Functional enrichment analysis showed that the regulation of cytokine-cytokine receptor interactions and immune cell function play a corresponding role in the progression of DN. The final 10 hub genes were identified through multiple datasets. In addition, the expression levels of the identified hub genes were corroborated through a rat model. The RF model exhibited the highest AUC. CIBERSORT analysis and single-cell sequencing analysis revealed changes in immune infiltration patterns between control subjects and DN patients. Several potential drugs to reverse the altered hub genes were identified through the Drug-Gene Interaction database (DGIdb)., Conclusion: This pioneering work provided a novel immunological perspective on the progression of DN, identifying key immune-related genes and potential drug targets, thus stimulating future mechanistic research and therapeutic target identification for DN., Competing Interests: All the authors have declared that they have no conflicts of interest regarding this article., (© 2023 Peng et al.)

Reactive oxygen species (ROS)-mediated tumor catalytic therapy is typically hindered by gap junction proteins that form cell-to-cell channels to remove cytotoxic ROS, thereby protecting tumor cells from oxidative damage. In this work, a multifunctional nanozyme, FePGOGA, is designed and prepared by Fe(III)-mediated oxidative polymerization (FeP), followed by glucose oxidase (GOx) and GAP19 peptides co-loading through electrostatic and π-π interactions. The FePGOGA nanozyme exhibits excellent cascade peroxidase- and glutathione-oxidase-like activities that efficiently catalyze hydrogen peroxide conversion to hydroxyl radicals and convert reduced glutathione to oxidized glutathione disulfide. The loaded GOx starves the tumors and aggravates tumor oxidative stress through glucose decomposition, while GAP19 peptides block the hemichannels by inducing degradation of Cx43, thus increasing the accumulation of intracellular ROS, and decreasing the transport of intracellular glucose. Furthermore, the ROS reacts with primary amines of heat shock proteins to destroy their structure and function, enabling tumor photothermal therapy at the widely sought-after mild temperature (mildPTT, ≤45 °C). In vivo experiments demonstrate the significant antitumor effectof FePGOGA on cal27 xenograft tumors under near-infrared light irradiation. This study demonstrates the successful ablation of gap junction proteins to overcome resistance to ROS-mediated therapy, providing a regulator to suppress tumor self-preservation during tumor starvation, catalytic therapy, and mildPTT., (© 2023 Wiley-VCH GmbH.)

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).)

Cigarette smoke exposure is the major cause of chronic obstructive pulmonary disease (COPD). Cigarette smoke heightens the elevation of reactive oxygen species (ROS) and thus leads to apoptosis. Hyperuricemia has been considered as a risk factor for COPD. However, the underlying mechanism for this aggravating effect remains unclear. The current study sought to examine the role of high uric acid (HUA) in COPD using cigarette smoke extract (CSE) exposed murine lung epithelial (MLE-12) cells. Our data showed that CSE induced the increase of ROS, mitochondrial dynamics disorder, and apoptosis, while HUA treatment aggravated the effects of CSE. Further studies suggested that HUA decreased the expression of antioxidant enzyme-peroxiredoxin-2 (PRDX2). Overexpression of PRDX2 inhibited excessive ROS generation, mitochondrial dynamics disorder, and apoptosis induced by HUA. Knockdown of PRDX2 by small interfering RNA (siRNA) promoted ROS generation, mitochondrial dynamics disorder, and apoptosis in MLE-12 cells treated with HUA. However, antioxidant N-acetylcysteine (NAC) reversed the effects of PRDX2-siRNA on MLE-12 cells. In conclusion, HUA aggravated CSE-induced cellular ROS levels and led to ROS-dependent mitochondrial dynamics disorder and apoptosis in MLE-12 cells through downregulating PRDX2., 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 B.V. All rights reserved.)

Background: Incidental thyroid abnormalities found on magnetic resonance imaging (MRI) of the neck are not uncommon. This study aimed to investigate the prevalence of incidental thyroid abnormalities in the cervical spine MRI of the degenerative cervical spondylosis (DCS) population indicated for surgery and to identify patients who require additional workup based on the recommendations of the American College of Radiology (ACR)., Methods: All consecutive patients with DCS and indications for cervical spine surgery from October 2014 to May 2019 in the Affiliated Hospital of Xuzhou Medical University were reviewed. All MRI scans of the cervical spine routinely include the thyroid. Cervical spine MRI scans were retrospectively evaluated for the prevalence, size, morphologic characteristics, and location of incidental thyroid abnormalities., Results: A total of 1,313 patients were included in the analysis, 98 (7.5%) of whom were found to have incidental thyroid abnormalities. The most frequent thyroid abnormality was thyroid nodules (5.3%), followed by goiters (1.4%). Other thyroid abnormalities included Hashimoto thyroiditis (0.4%) and thyroid cancer (0.5%). There was a statistically significant difference in age and sex between patients with DCS with and without incidental thyroid abnormalities (P=0.018 and P=0.007). Stratified by age, the results showed that the highest incidence of incidental thyroid abnormalities was found in patients aged 71 to 80 years (12.4%). Eighteen patients (1.4%) needed further ultrasound (US) and relevant workups., Conclusions: Incidental thyroid abnormalities are common in cervical MRI, with a prevalence of 7.5% identified in patients with DCS. Incidental thyroid abnormalities are large or have suspicious imaging features, and further evaluation with a dedicated thyroid US examination should be completed before cervical spine surgery is undertaken., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-484/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Chronic pain patients often have anxiety disorders, and some of them suffer from anxiety even after analgesic administration. In this study, we investigated the role of AMPAR-mediated synaptic transmission in the ventromedial prefrontal cortex (vmPFC) in chronic pain-induced persistent anxiety in mice and explored potential drug targets. Chronic inflammatory pain was induced in mice by bilateral injection of complete Freund's adjuvant (CFA) into the planta of the hind paws; anxiety-like behaviours were assessed with behavioural tests; S-nitrosylation and AMPAR-mediated synaptic transmission were examined using biochemical assays and electrophysiological recordings, respectively. We found that CFA induced persistent upregulation of AMPAR membrane expression and function in the vmPFC of anxious mice but not in the vmPFC of non-anxious mice. The anxious mice exhibited higher S-nitrosylation of stargazin (an AMPAR-interacting protein) in the vmPFC. Inhibition of S-nitrosylation by bilaterally infusing an exogenous stargazin (C302S) mutant into the vmPFC rescued the surface expression of GluA1 and AMPAR-mediated synaptic transmission as well as the anxiety-like behaviours in CFA-injected mice, even after ibuprofen treatment. Moreover, administration of ZL006, a small molecular inhibitor disrupting the interaction of nNOS and PSD-95 (20 mg·kg -1 ·d -1 , for 5 days, i.p.), significantly reduced nitric oxide production and S-nitrosylation of AMPAR-interacting proteins in the vmPFC, resulting in anxiolytic-like effects in anxious mice after ibuprofen treatment. We conclude that S-nitrosylation is necessary for AMPAR trafficking and function in the vmPFC under chronic inflammatory pain-induced persistent anxiety conditions, and nNOS-PSD-95 inhibitors could be potential anxiolytics specific for chronic inflammatory pain-induced persistent anxiety after analgesic treatment., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

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.)

Objective: This study aimed to explore the relationship between the ramus intermedius (RI) and atherosclerosis in the bifurcation of the left coronary artery (LCA)., Methods: Screening patients who underwent CCTA from January to September 2021, 100 patients with RI (RI group) and 100 patients without RI (no-RI group) were randomly enrolled, Evaluation of RI distribution characteristics and left main coronary artery(LM),Left anterior descending branch(LAD),left circumflex branch(LCX) proximal segment plaque distribution, measurement of LAD-LCX bifurcation angle(∠LAD-LCX),Comparison of the three distribution characteristics with the incidence of plaques in the left main trunk bifurcation area (LM, LAD, LCX) between groups and within the RI group., Results: The difference in the incidence of plaques in the proximal LCX and the LM between the RI group and the no-RI group were not statistically significant (P > 0.05). The incidence of plaques in the proximal LAD in the RI group was significantly higher than that in the non-RI group (77% versus 53%, P < 0.05). However, there was no statistically significant difference between the two groups after PSM. A univariate logistic regression analysis revealed that an RI was a risk factor for plaque formation in the proximal LAD (P < 0.001), and a multivariate logistic regression analysis revealed that an RI was not an independent risk factor for plaque formation in the proximal LAD (P > 0.05). When compared within the RI group, the difference in the incidence of plaques in the proximal segment of LAD, the proximal segment of LCX, and the LM among the different distribution groups of RI was not statistically significant, respectively (P > 0.05)., Conclusion: RI is not an independent risk factor for atherosclerosis in the left coronary artery bifurcation zone, but it may indirectly increase the risk of atherosclerosis in the proximal segment of the LAD., (© 2023. The Author(s).)

Purpose: Investigating the changes of regional homogeneity (ReHo) values and both static and dynamic functional connectivity (FC) before and after Traditional Chinese Manual Therapy (Tuina) in patients with lumbar disk herniation (LDH) through resting-state functional magnetic resonance imaging (RS-fMRI). Based on this, we observe the effect of Tuina on the above abnormal changes., Methods: Patients with LDH ( n = 27) and healthy controls (HCs) ( n = 28) were recruited. The functional magnetic resonance imaging (fMRI) scanning was performed two times in LDH patients, before Tuina (time point 1, LDH-pre) and after the sixth Tuina (time point 2, LDH-pos). And for one time in HCs which received no intervention. The ReHo values were compared between LDH-pre and HCs. The significant clusters detected by ReHo analysis were selected as seeds to calculate static functional connectivity (sFC). We also applied the sliding-window to perform dynamic functional connectivity (dFC). To evaluate the Tuina effect, the mean ReHo and FC values (both static and dynamic) were extracted from significant clusters and compared between LDH and HCs., Results: In comparison to HCs, LDH patients displayed decreased ReHo in the left orbital part middle frontal gyrus (LO-MFG). For sFC analysis, no significant difference was found. However, we found decreased dFC variance between LO-MFG and the left Fusiform, and increased dFC variance in the left orbital inferior frontal gyrus and left precuneus. Both ReHo and dFC values revealed after Tuina, the brain activities in LDH patients were similar to HCs., Conclusion: The present study characterized the altered patterns of regional homogeneity in spontaneous brain activity and those of functional connectivity in patients with LDH. Tuina can reshape the function of the default mode network (DMN) in LDH patients, which may contribute to the analgesic effect of Tuina in LDH patients., 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 Chen, Wen, Chen, Jin, Liu, Wang, Kong, Ling, Huang, Chai, Zhao, Li, Xu, Jiang and Du.)

Background: Patients with hypertriglyceridemia (HTG) are prone to develop more severe acute pancreatitis (AP). However, the specific molecular mechanism still has not been elaborated clearly, and effective drugs for treating HTG-AP are not yet readily available. Baicalin is an ingredient isolated from a natural product that with potential to attenuate inflammation and pain in AP., Aims: The aim of the present study was to explore the effect of baicalin on HTG-AP and the possible mechanism involved., Methods: A mouse model of HTG-AP was successfully established by administering Poloxamer 407 and L-arginine intraperitoneally. We analyzed pathological changes, and performed TUNEL staining, DHE staining, and western blot to detect apoptosis, inflammation, oxidative stress, and B7H4/JAK2/STAT3 signaling in the pancreas., Results: Treatment with baicalin decreased serum triglyceride, cholesterol, lipase, amylase levels, and attenuated pancreatic edema. After intervention with baicalin, apoptosis and inflammation in HTG-AP mice were alleviated, as indicated by the decrease of Bax, cleaved-caspase-3, IL-6, TNF-α, and IL-1β. Baicalin also alleviated oxidative stress by decreasing NOX2, increasing SOD2 protein expression, and regulating Nrf2/Keap1 signaling in HTG-AP mice. Furthermore, baicalin decreased the upregulated B7H4/JAK2/STAT3 pathway in HTG-AP., Conclusions: In conclusion, our data suggested that baicalin could attenuate HTG-AP, possibly through regulating B7H4/JAK2/STAT3 signaling., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This study was performed to investigate the relationship between right ventricular free wall longitudinal strain (RVFWSL) and low cardiac output syndrome (LCOS) after surgical aortic valve replacement (SAVR) and to further explore its association with readmission within 2 years in patients who developed LCOS after SAVR., Methods: This single-center retrospective observational study involved consecutive patients who underwent SAVR at our hospital from May 2018 to June 2020. Preoperative echocardiography was obtained within 3 days before SAVR. The longitudinal strain of the right ventricle was analyzed using the right ventricle as the main section, and the RVFWSL and right ventricular four-chamber longitudinal strain (RV4CSL) were obtained. The primary observation was the occurrence of LCOS. The secondary prognostic indicators were mainly the readmission rates within 2 years., Results: In total, 146 patients were finally included in this study. The RVFWSL was significantly lower in the LCOS group than in the No-LCOS group (16.63 ± 2.10) vs. (23.95 ± 6.33), respectively; P < 0.001). The multivariate regression analysis showed that the RVFWSL was associated with LCOS (odds ratio, 1.676; 95% confidence interval, 1.258-2.232; P < 0.001). The receiver operating characteristic curve showed that the cut-off value for RVFWSL to predict LCOS was less than -18.3, with an area under the curve of 0.879, sensitivity of 100%, and specificity of 80.47%. The multivariate regression analysis showed that LCOS was an independent risk factor for readmission within 2 years in patients undergoing SAVR., Conclusion: Patients with RVFWSL (<-18.3%) may be an increased risker for LCOS after SAVR. The occurrence of LCOS after SAVR is Yong-jian Zhang a risk factor for readmission within 2 years. Right ventricular function monitoring may have some predictive value for the postoperative prognosis in patients undergoing SAVR., 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 Zhang, Chen, Dong, Shang, Ruan, Yan and Song.)

Background: The incidence of magnet ingestion by children has recently increased in China. Magnet ingestion is associated with an extremely high risk of gastrointestinal damage because loops of bowel can become trapped and squeezed between multiple magnets in different locations. However, the lack of imaging sensitivity makes clinical decision-making difficult., Objective: This study was conducted to investigate the performance of ultrasound in diagnosing gastrointestinal magnet ingestion in children., Methods: From April 2017 to February 2021, all children with a history of magnet ingestion or a diagnosis of gastrointestinal magnet as shown by x-ray or ultrasound in our hospital were included as study candidates. Patients who were lost to follow-up or had known malformations of the gastrointestinal tract were excluded. Eligible patients were those with surgical or endoscopic confirmation of gastrointestinal magnet, those who passed the magnet out of the alimentary tract without assistance, and those with confirmed absence of the magnet on abdominal x-ray examination after 1 month of conservative treatment. All eligible patients' ultrasound and x-ray examination data were evaluated. The sensitivity, specificity, and area under the curve (AUC) of ultrasound was calculated for diagnosing magnet ingestion, locating the magnet (stomach, small intestine, or colon), and confirming the phenomenon of wall entrapment., Results: Of 112 patients, 107 had a magnetic foreign body and 5 did not. Magnets were correctly detected by ultrasound in 97 patients, with an observed sensitivity of 90.65% and specificity of 100%. Satisfactory sensitivity was obtained for ultrasound localization of gastric magnets (96.30%) and small intestinal magnets (100.00%), but sensitivity for ultrasound localization of colonic magnets was relatively poor (73.33%). The discrimination of wall entrapment by ultrasound was good (AUC = 0.93), with an observed sensitivity and specificity of 92.00% and 93.62%, respectively., Conclusions: Ultrasound can be used to locate gastrointestinal magnets (in the stomach, small intestine, or colon) with good clinical efficacy in identifying wall entrapment., 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 Xin, Jia, Dong, Wang, Hu and Wang.)

Facial foreign body (FB) is common after trauma, but iatrogenic orbital FB is a rare and unexpected complication of facial FB removal surgery. We present the case of a 43-year-old man with a glass FB in his nose. During the operation, this FB broke into two pieces, and the larger one pierced into the left orbit, close to the eyeball. A three-dimensional (3D) model was made that accurately recreated the shape and position of the FB in the orbit, according to which the FB was removed. 3D-printing technology is a great tool when dealing with complex facial FB.

Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/β-catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/β-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI., (© 2022 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.)

Objective: This study aims to explore the actual meaning of "false positive filling defect" in left atrial appendage (LAA) computed tomography (CT) in patients with atrial fibrillation (AF), with transesophageal echocardiography (TEE) as the gold standard., Methods: Patients with AF undergoing cardiac CT angiography and TEE examinations for proposed radiofrequency catheter ablation between October 2020 and October 2021 were selected as the study subjects. Transesophageal echocardiography was taken as the "gold standard," and spontaneous echocardiographic contrast (SEC) and thrombus events were defined as positive events. The CT manifestations were classified into three groups (true positive, false positive, and true negative) to evaluate the differences in left atrium (LA) anterior-posterior diameter (LAAP), LA anterior wall thickness, and LAA orifice long diameter and short diameter, area, and depth between the three groups., Results: (1) There was no statistical difference in LA anterior wall thickness between the three groups (p > .05); there was a statistical difference in LAAP (only) between the true-positive group and the true-negative group (p < .05). (2) There was a statistical difference in LAA orifice long diameter, short diameter, and area between the true-positive group and the true-negative group as well as between the false-positive group and the true-negative group (p < .05). (3) There was a statistical difference in LAA depth between the true-positive group and the false-positive group as well as between the true-positive group and the true-negative group (p < .05). (4) The area under the receiver operator characteristic curve (AUC) of LAA depth affecting the LAA thrombus and SEC was 0.863 (confidence interval = 0.718-1.000), the sensitivity was 77.8%, and the specificity was 90.6% for predicting the occurrence of LAA thrombus and SEC in patients with nonvalvular AF (NVAF) and an LAA depth of ≥50.84 mm., Conclusions: There was a difference in LAA diameter between the TEE-based CT false-positive group and the other groups. A "CT false positive" is an objectively existing state, and CT might be able to identify the LAA hemodynamic disorder earlier than TEE. Furthermore, a CT + TEE combined application could more accurately evaluate LAA hemodynamics in patients with AF., (© 2022 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

To evaluate the change of leukocyte level caused by hyperuricemia, and to explore the relationship between leukocyte level and hypertension in elderly patients with hyperuricemia. A cross-sectional study of serum uric acid (UA) level was conducted in 1352 elderly people over 65 years old. The samples were divided into 3 categories according to the tertiles of leukocyte: Tertile 1, leukocyte ≤ 5.2 × 109/L; Tertile 2, leukocyte = 5.3-6.3 × 109/L; Tertile 3, leukocyte ≥ 6.4 × 109/L. Multiple logistic regression models were used for modeling relationships between leukocyte, hyperuricemia and hypertension. Human vascular endothelial cells were treated by different concentrations of UA. The levels of interleukin-1 beta, tumor necrosis factor-α, endothelial nitric oxide synthase, inducible nitric oxide synthase and reactive oxygen species were measured by Western Blot or fluorescence microscope. The levels of leukocyte were higher in elderly patients with hyperuricemia than without hyperuricemia. Hyperuricemia was an independent risk factor of leukocyte in Tertile 3 (odds ratio [OR] = 1.657, 95% confidence interval [CI]: 1.180-2.328). The prevalences of hypertension were higher in elderly patients with hyperuricemia than without hyperuricemia (77.0% vs 63.5%). In the Model 1, hyperuricemia was an independent risk factor of hypertension (OR = 1.536, 95% CI: 1.026-2.302). Leukocyte in Tertile 3 was an independent risk factor of hypertension (OR = 1.333, 95% CI: 1.031-1.724). Expression levels of interleukin-1 beta, inducible nitric oxide synthase and tumor necrosis factor-α were obviously higher in the UA group than the control group, along with the productions of reactive oxygen species. But the expression level of endothelial nitric oxide synthase was obviously lower in the UA group. Hyperuricemia was associated with an increased risk for hypertension. The chronic inflammation caused by hyperuricemia maybe one of important pathogenesis of incident hypertension in patients with hyperuricemia., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

A two-dimensional grid-like coordination polymer, [Fe(NCBH 3 ) 2 (Py 2 ttz) 2 ]·4CHCl 3 ( 1·4CHCl 3 , Py 2 ttz = 2,5-di(pyridin-4-yl)thiazolo[5,4- d ]thiazole), showed one-step complete spin crossover with unexpectedly large hysteresis loop of 64 K wide and temperature-induced excited spin-state trapping effect below 91 K.

The selective cleavage of C-C bonds is of fundamental interest because it provides an alternative approach to traditional chemical synthesis, which is focused primarily on building up molecular complexity. However, current C-C cleavage methods provide only limited opportunities. For example, selective C(sp 3 )-C(sp 3 ) bond cleavage generally relies on the use of transition-metal to open strained ring systems or iminyl and alkoxy radicals to induce β-fragmentation. Here we show that by merging photoredox catalysis with copper catalysis, we are able to employ α-trisubstituted carboxylic acids as substrates and achieve consecutive C-C bond cleavage, resulting in the scission of the inert β-CH 2 group. The key transformation relies on the decarboxylative oxidation process, which could selectively generate in-situ formed alkoxy radicals and trigger consecutive C-C bond cleavage. This complicated yet interesting reaction might help the development of other methods for inert C(sp 3 )-C(sp 3 ) bond cleavage., (© 2022. The Author(s).)

Background: Artificial intelligence (AI) algorithms are capable of automatically detecting contouring boundaries in medical images. However, the algorithms impact on clinical practice of cervical cancer are unclear. We aimed to develop an AI-assisted system for automatic contouring of the clinical target volume (CTV) and organs-at-risk (OARs) in cervical cancer radiotherapy and conduct clinical-based observations., Methods: We first retrospectively collected data of 203 patients with cervical cancer from West China Hospital. The proposed method named as SegNet was developed and trained with different data groups. Quantitative metrics and clinical-based grading were used to evaluate differences between several groups of automatic contours. Then, 20 additional cases were conducted to compare the workload and quality of AI-assisted contours with manual delineation from scratch., Results: For automatic CTVs, the dice similarity coefficient (DSC) values of the SegNet trained with incorporating multi-group data achieved 0.85 ± 0.02, which was statistically better than the DSC values of SegNet independently trained with the SegNet (A) (0.82 ± 0.04), SegNet (B) (0.82 ± 0.03) or SegNet (C) (0.81 ± 0.04). Moreover, the DSC values of the SegNet and UNet, respectively, 0.85 and 0.82 for the CTV (P < 0.001), 0.93 and 0.92 for the bladder (P = 0.44), 0.84 and 0.81 for the rectum (P = 0.02), 0.89 and 0.84 for the bowel bag (P < 0.001), 0.93 and 0.92 for the right femoral head (P = 0.17), and 0.92 and 0.91 for the left femoral head (P = 0.25). The clinical-based grading also showed that SegNet trained with multi-group data obtained better performance of 352/360 relative to it trained with the SegNet (A) (334/360), SegNet (B) (333/360) or SegNet (C) (320/360). The manual revision time for automatic CTVs (OARs not yet include) was 9.54 ± 2.42 min relative to fully manual delineation with 30.95 ± 15.24 min., Conclusion: The proposed SegNet can improve the performance at automatic delineation for cervical cancer radiotherapy by incorporating multi-group data. It is clinically applicable that the AI-assisted system can shorten manual delineation time at no expense of quality., (© 2022. The Author(s).)

Major depressive disorder (MDD) is one of the most common mental disorders. We designed a fast-onset antidepressant that works by disrupting the interaction between the serotonin transporter (SERT) and neuronal nitric oxide synthase (nNOS) in the dorsal raphe nucleus (DRN). Chronic unpredictable mild stress (CMS) selectively increased the SERT-nNOS complex in the DRN in mice. Augmentation of SERT-nNOS interactions in the DRN caused a depression-like phenotype and accounted for the CMS-induced depressive behaviors. Disrupting the SERT-nNOS interaction produced a fast-onset antidepressant effect by enhancing serotonin signaling in forebrain circuits. We discovered a small-molecule compound, ZZL-7, that elicited an antidepressant effect 2 hours after treatment without undesirable side effects. This compound, or analogous reagents, may serve as a new, rapidly acting treatment for MDD.

Purpose: Lumbar disc herniation (LDH) is one of the leading causes of low-back pain and results in a series of clinical symptoms, including pain, reflex loss, and muscle weakness. Spinal manipulative therapy (SMT) can relieve pain and promote internal and external stabilization of the lumbar spine. In this study, we investigated whether the brain alterations of LDH patients with SMT were frequency-dependent based on the calculation of Amplitude of Low-Frequency Fluctuations (ALFF) and fractional ALFF (fALFF). Further, we established a cohort of LDH patients to evaluate the contribution of SMT treatments to brain functional reorganization., Methods: A total of 55 participants, including 27 LDH patients and 28 health controls (HCs), were collected. All LDH patients underwent two fMRI scans (before SMT and after the sixth SMT session). To represent LDH-related brain oscillatory activities, we calculated the ALFF and fALFF in the conventional band (0.01-0.08 Hz), the slow-4 band (0.027-0.073 Hz), and the slow-5 band (0.01-0.027 Hz). Moreover, we extracted ALFF and fALFF values in clusters with significant differences to evaluate the SMT effect., Results: Compared with HCs, the LDH patients before SMT (LDH-pre) exhibited increased fALFF in right lingual gyri in the conventional band, and showed increased fALFF in left Cerebelum&#95;Crus1 in the slow-4 band. We further examined the abnormal brain activities changes before and after the SMT intervention. The ALFF and fALFF values of LDH-pre group were higher than those of the HCs and LDH-pos groups. After SMT, the increased ALFF and fALFF values were suppressed for patients in conventional band and slow-4 band., Conclusion: The present study characterized the altered regional patterns in spontaneous neural activity in patients with LDH. Meanwhile, SMT is an effective treatment of LDH, and we supposed that it might have been involved in modulating dysfunctional brain regions which are important for the processing of pain. The findings of the current study may provide new insights to understand pathological mechanism of LDH., 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 © 2022 Wen, Chen, Jin, Ling, Chen, Huang, Kong, Chai, Wang, Xu and Du.)