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Zhu-Quan Su,* Wan-Yuan Rao,* Xiao-Yi Pan, Jia-Xin Tang, Ming-Yue Fan, Xiao-Bo Chen, Shi-Yue Li State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shi-Yue Li; Xiao-Bo Chen, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, 510120, People’s Republic of China, Tel +86 20 8306 2896, Email lishiyue@188.com; xiaobo-win@163.comAbstract: Disseminated infection caused by Streptococcus constellatus was seldom occurred. We reported a case of Streptococcus constellatus infection, presenting as multiple pulmonary cavities, thoracic wall abscess and vertebral destruction. The 37-year-old male had recurrent fever, chest wall swelling and pain, and lower limb numbness, he had weak physical condition and previously suffered from poorly controlled diabetes and severe periodontal disease for 3 years. Definite diagnosis of Streptococcus constellatus infection was made by metagenomic next‑generation sequencing (mNGS) in abscess drainage fluid. Systemic antibiotics and thoracic wall drainage were given, and the pulmonary cavity and the thoracic intermuscular abscess were significantly decreased. Few to no study reported the disseminated infection (pulmonary cavities, thoracic wall abscess and vertebral destruction) caused by Streptococcus constellatus. This case report highlighted the importance of mNGS for accurate diagnosis, as well as the timely drainage and antibiotics for effective treatment of Streptococcus constellatus infection.Keywords: Streptococcus constellatus, pulmonary cavity, thoracic wall abscess, vertebral destruction, metagenomic next‑generation sequencing

Chang Yan,1 De-Song Shen,1 Xiao-Bo Chen,2 Dan-Ke SU,3 Zhong-Guo Liang,1 Kai-Hua Chen,1 Ling Li,1 Xia Liang,1 Hai Liao,3 Xiao-Dong Zhu1,4 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2School of First Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 3Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 4Affiliated Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530100, People’s Republic of ChinaCorrespondence: Xiao-Dong ZhuDepartment of Radiation Oncology, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Nanning City, Guangxi, 530021, People’s Republic of ChinaTel +86 771 533 1466Email zhuxdonggxmu@126.comHai LiaoDepartment of Radiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of ChinaTel +86 771 533 4950Email 42442427@qq.comPurpose: We aimed to construct of a nomogram to predict progression-free survival (PFS) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) with risk stratification using computed tomography (CT) radiomics features and clinical factors.Patients and Methods: A total of 311 patients diagnosed with LA-NPC (stage III–IVa) at our hospital between 2010 and 2014 were included. The region of interest (ROI) of the primary nasopharyngeal mass was manually outlined. Independent sample t-test and LASSO-logistic regression were used for selecting the most predictive radiomics features of PFS, and to generate a radiomics signature. A nomogram was built with clinical factors and radiomics features, and the risk stratification model was tested accordingly.Results: In total, 20 radiomics features most associated with prognosis were selected. The radiomics nomogram, which integrated the radiomics signature and significant clinical factors, showed excellent performance in predicting PFS, with C-index of 0.873 (95% CI: 0.803∼ 0.943), which was better than that of the clinical nomogram (C-index, 0.729, 95% CI: 0.620∼ 0.838) as well as of the TNM staging system (C-index, 0.689, 95% CI: 0.592– 0.787) in validation cohort. The calibration curves and the decision curve analysis (DCA) plot obtained suggested satisfying accuracy and clinical utility of the model. The risk stratification tool was able to predict differences in prognosis of patients in different risk categories (p< 0.001).Conclusion: CT-based radiomics features, an in particular, radiomics nomograms, have the potential to become an accurate and reliable tool for assisting with prognosis prediction of LA-NPC.Keywords: computed tomography, locoregionally advanced nasopharyngeal carcinoma, radiomics, nomogram

Xiao-Bo Chen,1,* Rui-Ying Yan,2,* Ke Zhao,3,4,* Da-Fu Zhang,2 Ya-Jun Li,3,4 Lin Wu,5 Xing-Xiang Dong,2 Ying Chen,1 De-Pei Gao,2 Ying-Ying Ding,2 Xi-Cai Wang,6 Zhen-Hui Li2 1First Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, People’s Republic of China; 2Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, People’s Republic of China; 3Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, People’s Republic of China; 4School of Medicine, South China University of Technology, Guangzhou 510641, People’s Republic of China; 5Department of Pathology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, People’s Republic of China; 6Cancer Research Institute, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xi-Cai WangCancer Research Institute, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, No.519 Kun Zhou Road, Xi shan District, Kunming 650118, People’s Republic of ChinaTel +86 13888087351Email wangxc2005323@126.comZhen-Hui LiDepartment of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, No.519 Kun Zhou Road, Xi shan District, Kunming 650118, People’s Republic of ChinaTel +86 13698736132Email lizhenhui621@qq.comPurpose: This study aimed to develop and validate a nomogram for predicting the malignancy of small (8–20 mm) solid indeterminate solitary pulmonary nodules (SPNs) in a Chinese population by using routine clinical and computed tomography data.Methods: The prediction model was developed using a retrospective cohort that comprised 493 consecutive patients with small indeterminate SPNs who were treated between December 2012 and December 2016. The model was independently validated using a second retrospective cohort comprising 216 consecutive patients treated between January 2017 and May 2018. The investigated variables included patient characteristics (e.g., age and smoking history), nodule parameters (e.g., marginal spiculation and significant enhancement), and tumor biomarker levels (e.g., carcinoembryonic antigen). A prediction model was developed by using multivariable logistic regression analysis, and the model’s performance was presented as a nomogram. The model was evaluated based on its discriminative ability, calibration, and clinical usefulness.Results: The developed nomogram was ultimately based on age, marginal spiculation, significant enhancement, and pleural indentation. The Harrell concordance index values were 0.869 in the training cohort (95% confidence interval: 0.837–0.901) and 0.847 in the validation cohort (95% confidence interval: 0.792–0.902). The Hosmer-Lemeshow test revealed good calibration in each of the training and validation cohorts. Decision curve analysis confirmed that the nomogram was clinically useful (risk threshold from 0.10 to 0.85).Conclusion: Patient age, marginal spiculation, significant enhancement, and pleural indentation are independent predictors of malignancy in small indeterminate solid SPNs. The developed nomogram is easy-to-use and may allow the accurate prediction of malignancy in small indeterminate solid SPNs among Chinese patients.Keywords: lung cancer, solitary pulmonary nodule, solid nodule, nomogram, China

Zhu-Quan Su,1,* Wei-Jie Guan,1,* Shi-Yue Li,1,* Ming Ding,2 Yu Chen,1 Mei Jiang,1 Xiao-Bo Chen,1 Chang-Hao Zhong,1 Chun-Li Tang,1 Nan-Shan Zhong1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Respiratory Medicine, The Affiliated Zhongda Hospital of Southeast University, Medical School of Southeast University, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: Spirometry confers limited value for identifying small-airway disorders (SADs) in early-stage COPD, which can be detected with impulse oscillometry (IOS) and endobronchial optical coherence tomography (EB-OCT). Whether IOS is useful for reflecting small-airway morphological abnormalities in COPD remains unclear. Objectives: To compare the diagnostic value of spirometry and IOS for identifying SADs in heavy-smokers and COPD based on the objective assessment with EB-OCT. Methods: We recruited 59 COPD patients (stage I, n=17; stage II, n=18; stage III–IV, n=24), 26 heavy-smokers and 21 never-smokers. Assessments of clinical characteristics, spirometry, IOS and EB-OCT were performed. Receiver operation characteristic curve was employed to demonstrate the diagnostic value of IOS and spirometric parameters. Results: More advanced staging of COPD was associated with greater abnormality of IOS and spirometric parameters. Resonant frequency (Fres) and peripheral airway resistance (R5–R20) conferred greater diagnostic values than forced expiratory volume in one second (FEV1%) and maximal (mid-)expiratory flow (MMEF%) predicted in discriminating SADs in never-smokers from heavy-smokers (area under curve [AUC]: 0.771 and 0.753 vs 0.570 and 0.558, respectively), and heavy-smokers from patients with stage I COPD (AUC: 0.726 and 0.633 vs 0.548 and 0.567, respectively). The combination of IOS (Fres and R5–R20) and spirometric parameters (FEV1% and MMEF% predicted) contributed to a further increase in the diagnostic value for identifying SADs in early-stage COPD. Small airway wall area percentage (Aw% 7–9), an EB-OCT parameter, correlated significantly with Fres and R5–R20 in COPD and heavy-smokers, whereas EB-OCT parameters correlated with FEV1% and MMEF% in advanced, rather than early-stage, COPD. Conclusions: IOS parameters correlated with the degree of morphologic abnormalities of small airways assessed with EB-OCT in COPD and heavy-smokers. Fres and R5–R20 might be sensitive parameters that reliably reflect SADs in heavy-smokers and early-stage COPD. Keywords: chronic obstructive pulmonary disease, optical coherence tomography, diagnostic value, impulse oscillometry, small airway disorder

BACKGROUND AND PURPOSE Prostaglandin E2 (PGE2) stimulation of the G protein-coupled prostanoid EP1 receptor was found to up-regulate the expression of Nur-related factor 1 (Nurr1) (NR4A2), a transcription factor in the NR4A subfamily of nuclear receptors. The present studies characterize the molecular mechanism of this up-regulation. EXPERIMENTAL APPROACH The expression of Nurr1 was examined by immunoblot analysis, the polymerase chain reaction and reporter gene assays in human embryonic kidney (HEK) cells stably expressing the recombinant EP1 receptor and in SH-SY5Y neuroblastoma cells expressing endogenous EP1 receptors. Signalling pathway inhibitors were used to examine the roles of Rho, PKA, the cAMP response element binding protein (CREB) and NF-κB on the PGE2 stimulated up-regulation of Nurr1. CREB and NF-κB signalling were also examined by immunoblot analysis and reporter gene assays. KEY RESULTS The EP1 receptor mediated up-regulation of Nurr1 was blocked with inhibitors of Rho, PKA, NF-κB and CREB; but PGE2 failed to significantly stimulate intracellular cAMP formation. PGE2 stimulation of the EP1 receptor induced the phosphorylation and activation of CREB and NF-κB, which could be blocked by inhibition of PKA. CONCLUSIONS AND IMPLICATIONS PGE2 stimulation of the human EP1 receptor up-regulates the expression of Nurr1 by a mechanism involving the sequential activation of the Rho, PKA, CREB and NF-κB signalling pathways. EP1 receptors are implicated in tumorigenesis and the up-regulation of Nurr1 may underlie the anti-apoptotic effects of PGE2. [ABSTRACT FROM AUTHOR]

Targeting ABCB1 is a promising strategy in combating multidrug resistance. Our cell-based phenotypic screening led to the discovery of novel triazolo[1,5- a ]pyrimidone-based ABCB1 modulators. Notably, WS-917 was identified as a significant contributor to heightened sensitization of human colorectal adenocarcinoma cells (SW620/Ad300) to paclitaxel (IC 50 = 5 nM). Mechanistic elucidation revealed that this compound substantially augmented intracellular paclitaxel and [ 3 H]-paclitaxel, concurrently mitigating the efflux of [ 3 H]-paclitaxel in SW620/Ad300 through the inhibition of ABCB1 efflux. The cellular thermal shift assay underscored its ability to stabilize ABCB1 through direct binding. Additionally, WS-917 induced stimulation of ABCB1 ATPase activity while exhibiting negligible inhibitory effect against CYP3A4. Remarkable was its capacity to enhance the sensitivity of SW620/Ad300 to paclitaxel, as well as the sensitivity of CT26/TAXOL to paclitaxel and PD-L1 inhibitor (Atezolizumab) in vivo, all achieved without inducing observable toxicity. The discovery of WS-917 holds promise for the development of more potent ABCB1 modulators.

The evolution of hypervirulent and carbapenem-resistant Klebsiella pneumoniae can be categorized into three main patterns: the evolution of KL1/KL2-hvKp strains into CR-hvKp, the evolution of carbapenem-resistant K. pneumoniae (CRKp) strains into hv-CRKp, and the acquisition of hybrid plasmids carrying carbapenem resistance and virulence genes by classical K. pneumoniae (cKp). These strains are characterized by multi-drug resistance, high virulence, and high infectivity. Currently, there are no effective methods for treating and surveillance this pathogen. In addition, the continuous horizontal transfer and clonal spread of these bacteria under the pressure of hospital antibiotics have led to the emergence of more drug-resistant strains. This review discusses the evolution and distribution characteristics of hypervirulent and carbapenem-resistant K. pneumoniae, the mechanisms of carbapenem resistance and hypervirulence, risk factors for susceptibility, infection syndromes, treatment regimens, real-time surveillance and preventive control measures. It also outlines the resistance mechanisms of antimicrobial drugs used to treat this pathogen, providing insights for developing new drugs, combination therapies, and a "One Health" approach. Narrowing the scope of surveillance but intensifying implementation efforts is a viable solution. Monitoring of strains can be focused primarily on hospitals and urban wastewater treatment plants., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier GmbH. All rights reserved.)

To investigate the impact of vaccines on sociodemographic characteristics, clinical profiles, and outcomes of SARS-CoV-2 infection among healthcare workers in South China during the period of Omicron variant dominance, a retrospective, analytical cross-sectional study was conducted. The findings revealed that while full vaccination could not prevent Omicron variant infection efficiently (26.51% uninfected vs 14.29% uninfected between vaccinated and unvaccinated participants, p = 0.506), it did substantially reduce the length of viral clearance significantly (p < 0.05), potentially facilitating quicker patient recovery. Unvaccination was found to be an independent risk factor for slow clearance when a linear regression analysis model was used (Coefficient: -3.516; 95% CI: -6.425 to -0.607; p = 0.020). Therefore, all eligible individuals should be fully vaccinated to get prepared for a potential wave of epidemic in the future., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Acute myeloid leukemia (AML) is a malignant tumor with high recurrence and refractory rates and low survival rates. Increased glycolysis is characteristic of metabolism in AML blast cells and is also associated with chemotherapy resistance. The purpose of this study was to use gene expression and clinical information from The Cancer Genome Atlas (TCGA) database to identify subtypes of AML associated with lactate metabolism. Two different subtypes linked to lactate metabolism, each with specific immunological features and consequences for prognosis, were identified in this study. Using the TCGA and International Cancer Genome Consortium (GEO) cohorts, a prognostic model composed of genes (LMNA, RETN and HK1) for the prognostic value of the lactate metabolism-related risk score prognostic model was created and validated, suggesting possible therapeutic uses. Additionally, the diagnostic value of the prognostic model genes was explored. LMNA and HK1 were ultimately identified as hub genes, and their roles in AML were determined through immune infiltration, GeneMANIA, GSEA, methylation analysis and single-cell analysis. LMNA was upregulated in AML associating with a poor prognosis while HK1 was downregulated in AML associating with a favorable prognosis. The findings underscore the noteworthy impact of genes linked to lactate metabolism in AML and illustrate the possible therapeutic usefulness of the lactate metabolism-related risk score and the hub lactate metabolism-related genes in guiding AML patients' treatment choices., (© 2024. The Author(s).)

The function and survival of melanocytes is regulated by an elaborate network of paracrine factors synthesized mainly by epidermal keratinocytes (KCs). KCs and melanocytes respond to UV exposure by eliciting a tanning response. However, how KCs and melanocytes interact in the absence of UV exposure is unknown. In this study, we demonstrate that after SPRY1 knockout in epidermal KCs, melanocyte stem cells in the hair follicle exit the niche without depleting the pool of these cells. We also found that melanocyte stem cells migrate to the epidermis in a p53/stem cell factor/C-KIT-dependent manner induced by a tanning-like response resulting from SPRY1 loss in epidermal KCs. Once there, these cells differentiate into functional melanocytes. These findings provide an example in which the migration of melanocyte stem cells to the epidermis is due to loss of SPRY1 in epidermal KCs and show the potential for developing therapies for skin pigmentation disorders by manipulating melanocyte stem cells., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Since the discovery in 2000, conversion-type materials have emerged as a promising negative-electrode candidate for next-generation batteries with high capacity and tunable voltage, limited by low reversibility and severe voltage hysteresis. Heterogeneous construction stands out as a cost-effective and efficient approach to reducing reaction barriers and enhancing energy density. However, the second term introduced by conventional heterostructure inevitably complicates the electrochemical analysis and poses great challenges to harvesting systematic insights and theoretical guidance. A model cell is designed and established herein for the conversion reactions between Na and TM SA -SnO 2 , where TM SA -SnO 2 represents single atom modification of eight different 3d transition elements (V, Cr, Mn, Fe, Co, Ni, Cu or Zn). Such a model unit fundamentally eliminates the interference from the second phase and thus enables independent exploration of activation manifestations of the heterogeneous architecture. For the first time, a thermodynamically dependent catalytic effect is proposed and verified through statistical data analysis. The mechanism behind the unveiled catalytic effect is further elucidated by which the active d orbitals of transition metals weaken the surface covalent bonds and lower the reaction barriers. This research provides both theoretical insights and practical demonstrations of the advanced heterogeneous electrodes., (© 2024 Wiley-VCH GmbH.)

This article aims to develop CeO 2 nanocontainer-constructed coating with a synergistic self-healing and protective nature through a simple mechanical blending technique to manage metal corrosion. The proposed coating exhibits excellent corrosion resistance, which is primarily attributed to the combination of thermal-driven healing and active corrosion inhibition. Paraffin wax and 2-polybenzothiazole-loaded CeO 2 nanotubes (CeO 2 -MBT) are directly doped into epoxy coating to perform such a multifunctional role. CeO 2 nanocontainers and encapsulated corrosion inhibitor MBT can be released by pH triggers to achieve instant corrosion inhibition upon the surface of metal substrate. In addition, any physical defects in the coating are responsively repaired by heating incorporated paraffin wax to regain structural integrity and consequent barrier function. Corrosion protection efficiency remains sufficient even after ten cycles of damage and healing. Such a multiple-functional coating strategy provides an alternative pathway toward efficient and sustainable performance to tackle corrosion-related challenges of metal components in both short-term and long-term services., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

LSD1 (histone lysine-specific demethylase 1) has been gradually disclosed to act as an immunomodulator to enhance antitumor immune response. Despite the identification of numerous potent LSD1 inhibitors, there remains a lack of LSD1 inhibitors approved for marketing. Novel LSD1 inhibitors with different mechanisms are therefore needed. Herein, we reported a series of novel quinazoline-based LSD1 inhibitors. Among them, compound Z-1 exhibited the best LSD1 inhibitory activity (IC 50 = 0.108 μM). Z-1 also acted as a selective and cellular active as an LSD1 inhibitor. Furthermore, Z-1 promoted response of gastric cancer cells to T-cell killing effect by decreasing PD-L1 expression and further attenuated the PD-1/PD-L1 interaction. In vivo, Z-1 exhibited significant suppression effect on the growth of gastric cancer cells without obvious toxicity. Therefore, Z-1 represents a potential novel immunomodulator that targets LSD1, providing a lead compound with new function mechanism for gastric cancer treatment.