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An-An Li,1,2 Yu Zhang,1,2 Wei-Lai Tong,1,2 Jiang-Wei Chen,1 Shan-Hu Huang,1 Jia-Ming Liu,1 Zhi-Li Liu1,2 1Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Medical Innovation Center, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Zhi-Li Liu; Jia-Ming Liu, Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang, 330006, People’s Republic of China, Tel/Fax +86-791-88693201, Email liuzhiliyfy@163.com; zgm7977@ncu.edu.cn; liujiamingdr@hotmail.comPurpose: Pyroptosis plays an important role in the occurrence and progression of many tumors; however, the specific mechanisms involved remain unknown. Here, we construct a pyroptosis-related gene signature that can be used to predict survival prognosis of skin cutaneous melanoma (SKCM) and provide guidance for clinical treatment.Methods: By integrating data from the two databases from the GTEx and TCGA, differentially expressed genes (DEGs) from normal tissues and skin cutaneous tumor tissues were identified. The main signaling pathways and function enrichment of these differential genes were determined. Univariate and multivariate COX regression analysis, and risk score analysis were used to construct a signature to assess its predictive value for overall survival. The mRNA expression of these five genes in melanoma cells was determined by quantitative polymerase chain reaction (qPCR). The pRRophetic algorithm was used to estimate the half-maximal inhibitory concentration (IC50) of chemotherapy drugs in SKCM patients. The expression of multiple immune checkpoint genes also was evaluated.Results: Sixteen DEGs associated with pyroptosis in SKCM and normal skin tissues were identified. Of these, 12 pyroptosis-related DEGs were associated with the prognosis of SKCM. A five-gene signature (GSDMA, GSDMC, IL-18, NLRP6, and AIM2) model was constructed. Patients were divided into high-risk and low-risk groups using the risk scores. Of these, the high-risk group had a worse survival prognosis. There are significant differences in the predicted sensitivity of the high-risk and low-risk groups to chemotherapeutic drugs. In addition, compared with the high-risk group, the low-risk group showed higher expression of PD-1, PDL-1, CTLA-4, LAG-3, and VSIR.Conclusion: In this study, we constructed a novel prognostic pyroptosis-related gene-signature for SKCM. These genes showed good predictive value for patient prognosis and could provide guidance for better treatment of SKCM patients.Keywords: skin cutaneous melanoma, pyroptosis, prognosis, signature, risk model

Wen-Cai Liu,1,2 Ming-Xuan Li,2 Wen-Xing Qian,3 Zhi-Wen Luo,1,4 Wei-Jie Liao,1,4 Zhi-Li Liu,1,4 Jia-Ming Liu1,4 1Department of Orthopaedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 2The First Clinical Medical College of Nanchang University, Nanchang, 330006, People’s Republic of China; 3School of Computer and Information Technology, Beijing Jiaotong University, Beijing, 100044, People’s Republic of China; 4Institute of Spine and Spinal Cord, Nanchang University, Nanchang, 330006, People’s Republic of ChinaCorrespondence: Jia-Ming LiuDepartment of Orthopaedic Surgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi Province, People’s Republic of ChinaTel/Fax +86-791-86319815Email liujiamingdr@hotmail.comObjective: This study aimed to develop and validate a machine learning model for predicting bone metastases (BM) in prostate cancer (PCa) patients.Methods: Demographic and clinicopathologic variables of PCa patients in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2017 were retrospectively analyzed. We used six different machine learning algorithms, including Decision tree (DT), Random forest (RF), Multilayer Perceptron (MLP), Logistic regression (LR), Naive Bayes classifiers (NBC), and eXtreme gradient boosting (XGB), to build prediction models. External validation using data from 644 PCa patients of the First Affiliated Hospital of Nanchang University from 2010 to 2016. The performance of the models was evaluated using the area under receiver operating characteristic curve (AUC), accuracy score, sensitivity (recall rate) and specificity. A web predictor was developed based on the best performance model.Results: A total of 207,137 PCa patients from SEER were included in this study. Of whom, 6725 (3.25%) developed BM. Gleason score, Prostate-specific antigen (PSA) value, T, N stage and age were found to be the risk factors of BM. The XGB model offered the best predictive performance among these 6 models (AUC: 0.962, accuracy: 0.884, sensitivity (recall rate): 0.906, and specificity: 0.879). An XGB model-based web predictor was developed to predict BM in PCa patients.Conclusion: This study developed a machine learning model and a web predictor for predicting the risk of BM in PCa patients, which may help physicians make personalized clinical decisions and treatment strategy for patients.Keywords: prostate cancer, bone metastasis, machine learning, prediction model, SEER

Yuan Xue,1,2,* Pei-Dong Li,1,2,* Xue-Mei Tang,3,* Zai-Hua Yan,1,2 Shu-Sen Xia,1 Hong-Peng Tian,1 Zuo-Liang Liu,1 Tong Zhou,1 Xue-Gui Tang,4 Guang-Jun Zhang1,2 1The Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 2Institute of Hepatobiliary, Pancreatic and Intestinal Disease, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 3Department of Ultrasound, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 4Anorectal Department of Integrated Traditional Chinese and Western Medicine, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xue-Gui TangAnorectal Department of Integrated Traditional Chinese and Western Medicine, The Affiliated Hospital of North Sichuan Medical College, 63 Wenhua Road, Nanchong 637000, Sichuan, People’s Republic of ChinaTel +86 817 2262419Email txg668nc@sohu.comGuang-Jun ZhangThe Second Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, 63 Wenhua Road, Nanchong 637000, Sichuan, People’s Republic of ChinaTel +86 817 2262419Email zhanggj1977@126.comPurpose: Colorectal cancer (CRC) is one of the most common malignancies in the world. The prognosis of advanced CRC is still poor. The purpose of this study was to identify a gene expression profile associated with CRC that may contribute to the early diagnosis of CRC and improve patient prognosis.Patients and Methods: Five pairs of CRC tissues and paracancerous tissues were used to identify causative genes using microarray assays. The prognostic value of Cytochrome C Oxidase Assembly Factor 1 Homolog (COA1) in CRC was assessed in 90 CRC patients. Loss-of-function assays, cell proliferation assays using Celigo and MTT, colony formation assays, a subcutaneous xenograft mouse model, and apoptosis assays were used to define the effects of downregulation of COA1 in CRC cells in vitro and in vivo. The underlying molecular mechanisms of COA1 in CRC were also investigated.Results: The causative gene COA1 was identified through microarray analysis. COA1 expression in CRC was notably associated with pathologic differentiation, tumor size, and tumor depth. COA1 expression may act as an independent prognostic factor for overall survival of CRC. Knockdown of COA1 inhibited the proliferation of CRC cells in vitro and the tumorigenicity of CRC cells in vivo. Decreased COA1 expression induced apoptosis of CRC cells. Based on the microarray assay results comparing HCT116 cells transfected with lentivirus encoding anti-COA1 shRNA or negative control shRNA, ingenuity pathway analysis (IPA) revealed that the PI3K/AKT signaling pathway was significantly enriched. Moreover, CCND1, mTOR, AKT1, and MDM2 were identified as the downstream genes of COA1.Conclusion: These findings demonstrate that COA1 promotes CRC cell proliferation and inhibits apoptosis by regulating the PI3K/AKT signaling pathway. Our results implicate COA1 as a potential oncogene involved in tumor growth and progression of CRC.Keywords: colorectal cancer, COA1, proliferation, apoptosis, PI3K/AKT signaling

Fan Zhang,1 Lei Liu,2 Han Zhang,2 Zhe-Li Liu2 1Department of Ophthalmology, The Fourth Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Lens Research Laboratory of Liaoning Province, Shenyang, Liaoning, People’s Republic of China; 2Department of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Han ZhangDepartment of Ophthalmology, The First Affiliated Hospital of China Medical University, 155 Nanjing North St, Heping District, Shenyang 110001, Liaoning, People’s Republic of ChinaTel +86-24-83283590Fax +86-24-83282997Email zhanghan0614@139.comAim: To examine the effects of platelet-activating factor (PAF) on the barrier functions of cultured retinal pigment epithelial (RPE) cells.Methods: A human RPE cell line (ARPE-19) was cultured on microporous filter supports and treated with PAF and WEB 2086, a specific PAF-receptor (PAF-R) antagonist. The permeability of the RPE monolayer was measured using transepithelial electrical resistance (TER) and sodium fluorescein flux. The expression of the tight junction protein zonula occludens (ZO)-1 and the adherens junction protein N-cadherin was assessed using immunohistochemistry and Western blotting. We also measured the vascular endothelial growth factor (VEGF) concentrations in PAF-treated cultures and re-measured RPE monolayer permeability in the presence of VEGF-neutralizing antibodies.Results: PAF significantly decreased the TER and enhanced the sodium fluorescein flux of the RPE monolayer and downregulated the expression of ZO-1 and N-cadherin. These effects were abolished by WEB 2086-mediated blockage of the PAF-R. PAF stimulation increased VEGF expression in RPE cells, and the antibody-mediated neutralization of VEGF caused a partial recovery of the barrier properties.Conclusion: The barrier functions of ARPE-19 cells were altered by PAF, and these effects were partly mediated by an upregulation of VEGF expression in these cells. Our results contribute to the growing body of evidence supporting the role of PAF in choroidal neovascularization. Our findings suggest that PAF is a novel target in the development of therapies for increased permeability of the RPE monolayer.Keywords: platelet-activating factor, ARPE-19 cells, barrier function, vascular endothelial growth factor

Kaixiang Zhou,1 Chao Li,1 Dongmei Chen,2 Yuanhu Pan,1 Yanfei Tao,2 Wei Qu,2 Zhenli Liu,2 Xiaofang Wang,3 Shuyu Xie1 1MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, China; 2National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, Hubei, China; 3Animal Husbandry and Veterinary Institute of Hebei Province, Baoding, Hebei, China Abstract: Staphylococcus aureus (S. aureus) is an important zoonotic bacteria and hazardous for the health of human beings and livestock globally. The characteristics like biofilm forming, facultative intracellular survival, and growing resistance of S. aureus pose a great challenge to its use in therapy. Nanoparticles are considered as a promising way to overcome the infections’ therapeutic problems caused by S. aureus. In this paper, the present progress and challenges of nanoparticles in the treatment of S. aureus infection are focused on stepwise. First, the survival and infection mechanism of S. aureus are analyzed. Second, the treatment challenges posed by S. aureus are provided, which is followed by the third step including the advantages of nanoparticles in improving the penetration and accumulation ability of their payload antibiotics into cell, inhibiting S. aureus biofilm formation, and enhancing the antibacterial activity against resistant isolates. Finally, the challenges and future perspective of nanoparticles for S. aureus infection therapy are introduced. This review will help the readers to realize that the nanosystems can effectively fight against the S. aureus infection by inhibiting biofilm formation, enhancing intracellular delivery, and improving activity against methicillin-resistant S. aureus and small colony variant phenotypes as well as aim to help researchers looking for more efficient nanosystems to combat the S. aureus infections. Keywords: Staphylococcus aureus, infection mechanism, resistance, antibiotics, nanoparticles

Jing-Jing Yu,1,* Wen-Sen Pi,2,* Yuan Cao,3 Ai-Fen Peng,4 Zhi-Yuan Cao,2 Jia-Ming Liu,2 Shan-Hu Huang,2 Zhi-Li Liu,2 Wei Zhang1 1Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China; 2Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China; 3Department of Medical Imaging, The First Clinical Medical School of Nanchang University, Nanchang 330006, People’s Republic of China; 4College of Humanities, Jiangxi University of Traditional Chinese Medicine, Nanchang 330001, People’s Republic of China *These authors contributed equally to this work Purpose: Accumulating studies showed that the expression of microRNAs (miRNAs) was dysregulated in osteosarcoma (OS). In this study, we sought to investigate the effect of let-7a on OS progression and its potential molecular mechanism.Patients and methods: Quantitative real-time PCR (qRT-PCR) was performed to evaluate the expression level of let-7a and Aurora-B (AURKB) in OS tissues and cells. The OS cells were treated with let-7a mimic, let7a inhibitor, negative mimic and Lv-AURKB combined with let-7a. The ability of cell proliferation, migration and invasion was measured using Cell Counting Kit-8 (CCK-8) and wound-healing and transwell invasion assays. The protein of AURKB, NF-κβp65, MMP2 and MMP9 was measured by Western blot analysis. Xenograft model was performed to investigate the effects of let-7a on tumor growth and metastasis. The lung metastasis was measured by counting the metastatic node using H&E staining.Results: Let-7a expression was significantly underexpressed in OS cell lines and tissues compared with human osteoblast cell lines, hFOB1.19, and adjacent normal bone tissues. Exogenous let-7a inhibited the viability, migratory and invasive ability of OS cells in vitro. In addition, the overexpression of AURKB in OS cells could partly rescue let-7a-mediated tumor inhibition. Also, the overexpression of let-7a inhibited OS cell growth and lung metastasis in vivo. Furthermore, the results showed that let-7a could decrease the expression of NF-κβp65, MMP2 and MMP9 proteins by targeting AURKB in OS cells.Conclusion: Let-7a inhibits the malignant phenotype of OS cells by targeting AURKB at least partially. Targeting let-7a and AURKB/NF-κβ may be a novel therapeutic strategy for the treatment of OS. Keywords: let-7a, Aurora-B, osteosarcoma, malignant phenotype

Ze-Long Liu,* Xi-Wen Bi,* Pan-Pan Liu,* De-Xin Lei, Yu Wang, Zhi-Ming Li, Wen-Qi Jiang, Yi Xia Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre of Cancer Medicine, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: E2F transcription factors (E2Fs) are a family of transcription factors involved in cell proliferation, differentiation, and apoptosis. Their important roles in the development and metastasis of breast carcinoma (BC) have been discovered by previous in vitro and in vivo studies. Yet, expressions and distinct prognostic values of these eight E2Fs in human BC remain unclear in many respects. In this study, we aimed to reveal their roles in BC through analyzing the transcription and survival data of the E2Fs in BC patients from four online databases including ONCOMINE, Breast Cancer Gene-Expression Miner v4.1, cBioPortal for Cancer Genomics, and Kaplan–Meier Plotter. We found the overexpression of E2Fs in BC tissues compared with normal breast tissues, except for E2F4. Higher expression levels of E2Fs, except for E2F4 and E2F6, were associated with higher levels of Scarff–Bloom–Richardson grade of BC. Alterations of E2Fs were found to be significantly correlated with poorer overall survival of BC patients. Through plotting the survival curve in the Kaplan–Meier Plotter, it was found that higher mRNA levels of E2F1, E2F3, E2F7, and E2F8 were associated with poorer relapse-free survival in all BC patients, indicating that they are potential targets for individualized treatments of BC patients. Conversely, higher mRNA expression level of E2F4 predicted better RFS in BC patients, suggesting E2F4 as a new biomarker for BC prognosis. Considering currently available limited evidence, further studies need to be performed to investigate the roles of E2Fs in BC. Keywords: E2Fs, breast carcinoma, expressions, prognostic values, Kaplan–Meier plot

Wen-Kai Xia,1 Qing-Feng Lin,2 Dong Shen,2 Zhi-Li Liu,2 Jun Su,2 Wei-Dong Mao2 1Department of Nephrology, 2Department of Oncology, The Affiliated Jiangyin Hospital, School of Medicine, Southeast University, Jiangyin, Jiangsu, People’s Republic of China Abstract: Long noncoding RNAs have been documented as having widespread roles in carcinogenesis and cancer progression. However, roles of long noncoding RNAs in osteosarcoma remain unclear. This study is to investigate the clinical relevance and biological functions of long noncoding RNA 91H in osteosarcoma. Herein, we confirmed that 91H expression was notably increased in osteosarcoma patients and cell lines compared to healthy controls and normal human bone cell lines. High expression of 91H was significantly correlated with advanced clinical stage, chemotherapy after surgery, and tumor size >5 cm. Furthermore, 91H was an independent prognostic factor for overall survival in osteosarcoma patients after treatments. Additionally, the knockdown of 91H expression inhibited osteosarcoma cells’ proliferation and promoted their apoptosis in vitro. In summary, these findings indicate that 91H may be a novel biomarker for risk prognostication and also provide a clue to the molecular etiology of osteosarcoma. Keywords: long noncoding RNA, 91H, osteosarcoma, survival

Zhaoling Zheng,1,* YanHua Sun,2,* Ziliang Liu,1 Mingqin Zhang,1 Chunqing Li,1 Hui Cai3 1Department of Traditional Chinese Medicine, Dongying People’s Hospital, Dongying, 2Shandong Provincial Key Laboratory of Microparticles Drug Delivery Technology, Jinan, 3Department of Integrated Traditional Chinese Medicine and Western Medicine, Nanjing Jinling Hospital, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: Rheumatoid arthritis (RA), induced by the prolonged inappropriate inflammatory responses, is one of the most prevalent of all chronic inflammatory joint diseases. Curcumin (CM), a yellow hydrophobic polyphenol derived from the herb turmeric, has various pharmacological activities against many chronic diseases and acts by inhibiting cell proliferation and metastasis and downregulating various factors, including nuclear factor kappa B, interleukin-1β and TNF-α. Given the pathogenesis of RA, we hypothesized that the drug also has antiarthritic effects. The aims of the present study included the following: 1) examining the therapeutic effect of CM administered via intravenous (iv) injection on RA and 2) formulating the drug into oil–water nanoemulsions (Ns) to overcome the low oral bioavailability of CM and achieve oral delivery of the drug.Methods: The effect of CM administered through iv injection on adjuvant-induced arthritis in rats was studied in terms of paw swelling, weight indices of the thymus and spleen, and pathological changes in nuclear factor kappa B expression and inflammatory cytokines. Methotrexate was used as a positive control. The CM-Ns were prepared using a high-pressure homogenizing method and characterized with respect to the particle size and morphology. The stability of the CM-Ns in simulated gastrointestinal (GI) fluids and in vitro release were also investigated. A pharmacokinetic study of the CM-Ns and suspensions in which the plasma levels were determined using an high performance liquid chromatography method and the pharmacokinetic parameters were calculated based on a statistical moment theory was also performed in rats.Results: CM administered via iv injection had a therapeutic effect on RA similar to methotrexate. CM-Ns with a diameter of approximately 150 nm were successfully prepared, and the drug was well encapsulated into the Ns without degradation in simulated GI conditions. The area under the curve (AUC) and Cmax for the CM-Ns were more than threefold greater than those for the suspensions; moreover, similar decreases in the levels of TNF-α and interleukin-1β in both synovial fluid and blood serum were obtained from oral administration of CM-Ns and iv injection.Conclusion: CM was an effective antiarthritic agent, and the present N formulation appeared to be a promising system that allowed RA therapy with CM to be converted from iv to oral administration. Keywords: curcumin, nanoemulsions, inflammatory cytokines, adjuvant-induced arthritis, drug release, oral bioavailability

Objective: To explore the role and function of stromal cell-derived factor-1 (SDF-1) in stem cells migrating into injured brain area.Methods: Rat-derived nerve stem cells (NSCs) were isolated and cultured routinely. Transwell system was used to observe the migration ability of NSCs into injured nerve cells. Immunocytochemistry was used to explore the expression of chemotactic factor receptor-4 (CXCR-4) in NSCs. In vivo, we applied immunofluorescence technique to observe the migration of NSCs into injured brain area. Immunofluorescence technique and Western blotting were used to test expression level of SDF-1. After AMD3100 (a special chemical blocker) blocking CXCR-4, the migration ability of NSCs was tested in vivo and in vitro, respectively.Results: NSCs displayed specific tropism for injured nerve cells or traumatic brain area in vivo and in vitro. The expression level of SDF-1 in traumatic brain area increased remarkably and the expression level of CXCR-4 in the NSCs increased simultaneously. After AMD3100 blocking the expression of CXCR-4, the migration ability of NSCs decreased significantly both in vivo and in vitro.Conclusions: SDF-1 may play a key role in stem cells migrating into injured brain area through specially combining with CXCR-4. [ABSTRACT FROM AUTHOR]

Objective: To promote stem cells differentiation into neurons and enhance neuromotor function after brain injury through brain-derived neurotrophic factor (BDNF) induction.Methods: Recombinant adenovirus vector was applied to the transfection of BDNF into human-derived umbilical cord mesenchymal stem cells (UCMSCs). Enzyme linked immunosorbent assay (ELISA) was used to determine the secretion phase of BDNF. The brain injury model of athymic mice induced by hydraulic pressure percussion was established for transplantation of stem cells into the edge of injury site. Nerve function scores were obtained, and the expression level of transfected and non-transfected BDNF, proportion of neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and the number of apoptosis cells were compared respectively.Results: The BDNF expression achieved its stabilization at a high level 72 hours after gene transfection. The mouse obtained a better score of nerve function, and the proportion of the NSE-positive cells increased significantly (P<0.05), but GFAP-positive cells decreased in BDNF-UCMSCs group compared with the other two groups (P<0.05). At the site of high expression of BDNF, the number of apoptosis cells decreased markedly.Conclusion: BDNF gene can promote the differentiation of the stem cells into neurons rather than glial cells, and enhance neuromotor function after brain injury. [ABSTRACT FROM AUTHOR]

Objective: To provide anatomical basis for the internal fixation of scaphoid fractures.Methods: The shape and vascular lake of 48 dry scaphoids and 36 wet scaphoids were observed.Results: The data of dry bone group and wet bone group were as follows: the height of scaphoid tubercle were (11.28+/-0.94) mm and (10.35+/-1.54) mm; the thickness of scapoid waist were (12.02+/-1.90) mm and (11.21+/-1.20) mm; the width of scapoid waist were (10.59+/-1.11) mm and (11.34+/-1.47) mm; the minimal thickness of the body of scapoid were (6.51+/-1.22) mm and (8.54+/-1.07) mm; the axis length of scapoid were (25.68+/-2.21) mm and (26.50+/-2.56) mm; the width of epicondyle of scaphoid of distal portion, waist and proximal portion were (6.50+/-1.06) mm, (5.14+/-1.01) mm, (4.42+/-1.16) mm and (6.64+/-1.18) mm, (6.01+/-0.75) mm and (5.71+/-0.78) mm, respestively. The main blood vessels came from the dorsal and the radial of wrist and passed through the whole scaphoid along the crest of scaphoid.Conclusion: The internal fixation of scaphoid can be designed according to the anatomical data without damaging the articular surface and blood supply. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study., Objective: To evaluate the effectiveness of pedicle screw trajectory planning based on artificial intelligence (AI) software in patients with different levels of bone mineral density (BMD)., Summary of Background Data: AI-based pedicle screw trajectory planning has potential to improve pullout force (POF) of screws. However, there is currently no literature investigating the efficacy of AI-based pedicle screw trajectory planning in patients with different levels of BMD., Methods: The patients were divided into 5 groups (group A-E) according to their BMD. The AI software utilizes lumbar spine CT data to perform screw trajectory planning and simulate AO screw trajectories for bilateral L3-5 vertebral bodies. Both screw trajectories were subdivided into unicortical and bicortical modes. The AI software automatically calculating the POF and pullout risk of every screw trajectory. The POF and risk of screw pullout for AI-planned screw trajectories and AO standard trajectories were compared and analyzed., Results: Forty-three patients were included. For the screw sizes, AI-planned screws were greater in diameter and length than those of AO screws (P<0.05). In groups B-E, the AI unicortical trajectories had a POF of over 200N higher than that of AO unicortical trajectories. POF was higher in all groups for the AI bicortical screw trajectories compared with the AO bicortical screw trajectories (P<0.05). AI unicortical trajectories in groups B-E had a lower risk of screw pullout compared with that of AO unicortical trajectories (P<0.05)., Conclusions: AI unicortical screw trajectory planning for lumbar surgery in patients with BMD of 40-120 mg/cm3 can significantly improve screw POF and reduce the risk of screw pullout., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A highly enantioselective Pd/Bim-catalyzed dearomative Michael reaction applying polycyclic tropones as non-benzenoid aromatic Michael acceptors and arylboronic acids as aryl pronucleophiles has been developed. The bridged biaryls bearing central and axial chirality, including pentacyclic cyclohepta[ b ]indoles and 6,7-dihydrodibenzo[ a , c ][7]annulen-5-ones, are generally generated in good to high yields and excellent enantioselectivities and can be readily transformed into useful derivatives.

Background: Sepsis, a complex and life-threatening disease, poses a significant global burden affecting over 48 million individuals. Recently, it has been reported that programmed death-ligand 1 (PD-L1) expressed on neutrophils is involved in both inflammatory organ dysfunction and immunoparalysis in sepsis. However, there is a dearth of strategies to specifically target PD-L1 in neutrophils in vivo., Methods: We successfully developed two lipid nanoparticles (LNPs) specifically targeting neutrophils by delivering PD-L1 siRNA via neutrophil-specific antibodies and polypeptides. In vivo and in vitro experiments were performed to detect lipid nanoparticles into neutrophils. A mouse cecal ligation and puncture (CLP) model was used to detect neutrophil migration, neutrophil extracellular traps (NETs) level, and organ damage., Result: The PD-L1 siRNA-loaded LNPs that target neutrophils suppressed inflammation, reduced the release of NETs, and inhibited T-lymphocyte apoptosis. This approach could help maintain homeostasis of both the immune and inflammatory responses during sepsis. Furthermore, the PD-L1 siRNA-loaded LNPs targeting neutrophils have the potential to ameliorate the multi-organ damage and lethality resulting from CLP., Conclusions: Taken together, our data identify a previously unknown drug delivery strategy targeting neutrophils, which represents a novel, safe, and effective approach to sepsis therapy., (Copyright © 2024 by the Shock Society.)

The clearance of apoptotic cells, termed efferocytosis, is essential for tissue homeostasis and prevention of autoimmunity 1 . Although past studies have elucidated local molecular signals that regulate homeostatic efferocytosis in a tissue 2,3 , whether signals arising distally also regulate homeostatic efferocytosis remains elusive. Here, we show that large peritoneal macrophage (LPM) display impairs efferocytosis in broad-spectrum antibiotics (ABX)-treated, vancomycin-treated and germ-free mice in vivo, all of which have a depleted gut microbiota. Mechanistically, the microbiota-derived short-chain fatty acid butyrate directly boosts efferocytosis efficiency and capacity in mouse and human macrophages, and rescues ABX-induced LPM efferocytosis defects in vivo. Bulk messenger RNA sequencing of butyrate-treated macrophages in vitro and single-cell messenger RNA sequencing of LPMs isolated from ABX-treated and butyrate-rescued mice reveals regulation of efferocytosis-supportive transcriptional programmes. Specifically, we find that the efferocytosis receptor T cell immunoglobulin and mucin domain containing 4 (TIM-4, Timd4) is downregulated in LPMs of ABX-treated mice but rescued by oral butyrate. We show that TIM-4 is required for the butyrate-induced enhancement of LPM efferocytosis capacity and that LPM efferocytosis is impaired beyond withdrawal of ABX. ABX-treated mice exhibit significantly worse disease in a mouse model of lupus. Our results demonstrate that homeostatic efferocytosis relies on distal metabolic signals and suggest that defective homeostatic efferocytosis may explain the link between ABX use and inflammatory disease 4-7 ., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)