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Jian-Hong An,1 Chun-Yan Li,1 Chun-Ya Chen,1 Jian-Bin Wu,2 Hong Shen1,3 1School of Medicine, South China University of Technology, Guangzhou Higher Education Mega Center, Guangzhou, 510006, People’s Republic of China; 2Department of Oncology, First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 3Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of ChinaCorrespondence: Hong Shen Tel +86 20-61648227Fax +86 20-61648312Email shenhong2010168@163.comPurpose: Cisplatin is one of the most widely used antineoplastic drugs but has limited therapeutic effects due to nephrotoxicity. The aim of this study was to determine the possible renoprotective effect of the antioxidant raloxifene on cisplatin-induced nephrotoxicity in mice.Materials and Methods: Cisplatin-induced acute renal injury was established in female C57 mice that were treated with saline (normal control) or raloxifene over a 7-day period. The body weight of the mice was recorded. Histopathological examinations of the kidney tissues were performed using H&E, PAS staining and TEM. The histomorphology of liver and other organs was observed by H&E staining. The serum levels of creatinine, blood urea nitrogen (BUN), alanine transaminase (ALT) and glutamic oxalacetic transaminase (AST) were analyzed by specific kits. Superoxide dismutase (SOD) and glutathione (GSH) activity, and the content of malondialdehyde (MDA) in the kidney, liver homogenates and HK-2 cells were measured by WST-8 and thiobarbituric acid colorimetric methods. Moreover, the mitochondrial structures of HK-2 cells were performed using TEM. The viability and proliferation of HK-2 cells were examined by CCK-8 and EdU incorporation assays. The mitochondrial membrane potential was measured by JC-1 fluorescence.Results: Raloxifene significantly reduced the levels of serum creatinine, urea, ALT and AST in the cisplatin-treated mice, and alleviated cisplatin-induced renal and hepatic tissue injury. Furthermore, raloxifene also increased the activity of GSH and SOD in the renal tissues and HK-2 cells, and reduced MDA levels, thereby limiting oxidative stress in the kidney.Conclusion: Raloxifene protected against cisplatin-induced nephrotoxicity by activating the antioxidant system, along with alleviating liver damage. It should be considered as a potential adjuvant in cisplatin-based chemotherapeutic protocols.Keywords: raloxifene, cisplatin, nephrotoxicity, hepatotoxicity, oxidative stress

Chun-Yan Li,1 Chun-Ya Chen,1 Jian-Hong An,1 Jian-Bin Wu,2 Hong Shen1,3 1South China University of Technology School of Medicine, Guangzhou Higher Education Mega Center, Guangzhou, 510006, Guangdong, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510407, People’s Republic of China; 3Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of ChinaCorrespondence: Hong Shen Tel +86 20-61648227Email shenhong2010168@163.comAim: Basal epithelial cells are absent in distant prostate cancer. This study aimed to investigate whether basal epithelial cells could suppress migration and invasion of prostate cancer cells to become a new treatment strategy for prostate cancer.Main Methods: Basal epithelial cells were identified by immunofluorescence with anti-p63. Wound healing assays or transwell assays were used to explore the effects of basal epithelial cells, TGF-β 1, SB431542 (inhibitor of TGF-β type I receptor) or stattic (inhibitor of phosphorylated STAT3) on migration or invasion of mouse prostate cancer cell (RM-1). Concentration of TGF-β 1 was measured by ELISA assay. HE staining was used to investigate cell morphology. Immunocytochemistry with anti-p63 was used to identify basal epithelial cells. Levels of STAT3, p-STAT3 (Ser727) and proteins associated with EMT were measured with Western blot assay. Cell proliferation was measured with MTT or CCK8 assay.Results: Normal basal epithelial cells acquired from mouse prostate were specific to anti-p63 and more than 90%. Basal epithelial cells and RM-1 could both secrete TGF-β 1. Basal epithelial cells and TGF-β 1 promoted the migration and invasion of RM-1 through changing the cell morphology and up-regulating expression of ZEB1, N-cadherin, vimentin, snail and p-STAT3 (Ser727), at the same time down-regulating E-cadherin of RM-1. SB431542 strongly suppressed migration, invasion as well as the expressions of EMT relevant proteins and p-STAT3 (Ser727) of co-cultured RM-1. In addition, stattic suppressed proliferation, migration and invasion of non-treated RM-1 and co-cultured RM-1.Conclusion: Our study suggests that normal basal epithelial cells might stimulate the migration and invasion of RM-1 by TGF-β 1/STAT3 axis which could be suppressed by inhibitor of TGF-β receptor and inhibitor of p-STAT3. So, basal epithelial cells might not become a treatment strategy for prostate cancer, but our results could provide some researching references for other diseases which include basal epithelial cells such as prostatic intraepithelial neoplasia, prostatic hyperplasia, cervical cancer, or urinary bladder cancer.Keywords: normal basal epithelial cells, RM-1, migration, invasion, TGF-β 1, STAT3

Dong Li,1,* Chuanfei Hu,1,* Juan Yang,1 Yin Liao,1 Yue Chen,2,3 Shao Zhi Fu,1 Jing Bo Wu1,3 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, People’s Republic of China; 2Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, People’s Republic of China; 3Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Bo WuDepartment of Oncology, The Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Luzhou 646000, People’s Republic of ChinaEmail wjb6147@163.comShao Zhi FuDepartment of Oncology, The Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Luzhou 646000, People’s Republic of ChinaTel +86 830 316 5698Fax +86 830 316 5690Email shaozhifu513@163.comBackground: Radiotherapy (RT), one of the main treatments for cervical cancer, has tremendous potential for improvement in the efficacy. Poly (ADP-ribose) polymerase (PARP) is a key enzyme in the repair of DNA strand breaks (DSB). Olaparib (Ola) is a PARP inhibitor that is involved in preventing the release of PARP from RT-induced damaged DNA to potentiate the effect of RT. Although the basic mechanism of Ola’s radiosensitization is well known, the radiosensitization mechanism of its nanomedicine is still unclear. In addition, the lack of tumor tissue targeting is a major obstacle for the clinical success of Ola.Materials and Methods: In this study, we developed folate-conjugated active targeting olaparib nanoparticles (ATO) and investigated the anti-tumor effect of ATO combined with radiotherapy (RT) in nude mice using cervical cancer xenograft models. We used folate (FA)-conjugated poly (ϵ-caprolactone)-poly (ethyleneglycol)-poly (e-caprolactone) (PCEC) copolymer to prepare ATO via emulsification/solvent diffusion. Further, we evaluated ATO particle size, potential, encapsulation efficiency, and in vitro release characteristics, and evaluated the shape of ATO via transmission electron microscopy (TEM). We then performed MTT and cell uptake assays to detect cytotoxicity and targeting uptake in vitro. We investigated the anti-tumor properties of ATO in vivo by apoptosis test, 18 F-FDG PET/CT, and immunohistochemical analysis. Finally, the xenografted tumor in nude mice was subjected to RT and/or ATO treatment.Results: The results confirmed that ATO in combination with RT significantly inhibited tumor growth and prolonged survival time of tumor-bearing mice. This may be related to the inhibition of tumor proliferation and DNA damage repair and induction of cell apoptosis in vivo.Conclusion: The ATO developed in this study may represent a novel formulation for olaparib delivery and have promising potential for treating tumors with an over-expression of folate receptors.Keywords: olaparib, cervical cancer, folate, anti-cancer effect, active targeting

Wei-Xue Jia,1,2 Xue-Min Xiao,1,2 Jian-Bing Wu,1,2 Yi-Ping Ma,1,2 Yi-Ping Ge,1,2 Qi Li,1,2 Qiu-Xia Mao,1,2 Cheng-Rang Li1,2 1Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China; 2Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, Jiangsu, China Abstract: Piebaldism is a rare autosomal dominant genodermatosis, manifesting as congenital and stable depigmentation of the skin and white forelock. It has been found to be associated with mutations in the KIT or SLUG genes. We report a Chinese piebaldism family including a 28-year-old woman and her 3-year-old son with characteristics of white patches and forelock associated with numerous brown macules and patches. Genomic DNA samples of the proband and her son were extracted from their peripheral blood. One hundred unrelated healthy individuals were used as controls. All coding regions of KIT, SLUG, and NF1 genes were amplified by polymerase chain reaction using exon flanking intronic primers and Sanger sequencings were performed. DNA sequencing revealed heterozygous missense c.2431T>G mutation in exon 17 of the KIT gene in the proband and the affected son. No potentially pathogenic variant was identified in SLUG or NF1 genes. The nucleotide substitution was not found in 100 unrelated control individuals. This study reveals a novel KIT mutation in piebaldism, and it further supports that café-au-lait macules and intertriginous freckling of piebaldism are parts of pigmented anomaly in piebaldism, which does not necessarily represent coexistence of neurofibromatosis type 1 (NF1). Keywords: novel mutation, KIT gene, neurofibromatosis type 1

Objective: To analyze the spatial autocorrelation and spatiotemporal clustering characteristics of severe fever with thrombocytopenia syndrome(SFTS) in Anhui Province from 2011 to 2023., Methods: Data of SFTS in Anhui Province from 2011 to 2023 were collected. Spatial autocorrelation analysis was conducted using GeoDa software, while spatiotemporal scanning was performed using SaTScan 10.0.1 software to identify significant spatiotemporal clusters of SFTS., Results: From 2011 to 2023, 5720 SFTS cases were reported in Anhui Province, with an average annual incidence rate of 0.7131/100,000. The incidence of SFTS in Anhui Province reached its peak mainly from April to May, with a small peak in October. The spatial autocorrelation results showed that from 2011 to 2023, there was a spatial positive correlation(P < 0.05) in the incidence of SFTS in all counties and districts of Anhui Province. Local autocorrelation high-high clustering areas are mainly located in the south of the Huaihe River. The spatiotemporal scanning results show three main clusters of SFTS in recent years: the first cluster located in the lower reaches of the Yangtze River, the eastern region of Anhui Province; the second cluster primarily focused on the region of the Dabie Mountain range, while the third cluster primarily focused on the region of the Huang Mountain range., Conclusions: The incidence of SFTS in Anhui Province in 2011-2023 was spatially clustered., (© 2024. The Author(s).)

Our previous study has identified that glutamate in the red nucleus (RN) facilitates the development of neuropathic pain through metabotropic glutamate receptors (mGluR). Here, we further explored the actions and possible molecular mechanisms of red nucleus mGluR Ⅰ (mGluR1 and mGluR5) in the development of neuropathic pain induced by spared nerve injury (SNI). Our data indicated that both mGluR1 and mGluR5 were constitutively expressed in the RN of normal rats. Two weeks after SNI, the expressions of mGluR1 and mGluR5 were significantly boosted in the RN contralateral to the nerve injury. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN contralateral to the nerve injury at 2 weeks post-SNI significantly ameliorated SNI-induced neuropathic pain. However, unilateral administration of mGluRⅠ agonist DHPG to the RN of normal rats provoked a significant mechanical allodynia, this effect could be blocked by LY367385 or MTEP. Further studies indicated that the expressions of TNF-α and IL-1β in the RN were also elevated at 2 weeks post-SNI. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN at 2 weeks post-SNI significantly inhibited the elevations of TNF-α and IL-1β. However, administration of mGluR Ⅰ agonist DHPG to the RN of normal rats significantly enhanced the expressions of TNF-α and IL-1β, these effects were blocked by LY367385 or MTEP. These results suggest that activation of red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain by stimulating the expressions of TNF-α and IL-1β. mGluR Ⅰ maybe potential targets for drug development and clinical treatment of neuropathic pain., Competing Interests: Declaration of competing interest The authors have approved the manuscript entitled “Red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain through stimulating the expressions of TNF-α and IL-1β” and agreed with the submission to Neurochemistry International. All 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In-sensor and near-sensor computing architectures enable multiply accumulate operations to be carried out directly at the point of sensing. In-sensor architectures offer dramatic power and speed improvements over traditional von Neumann architectures by eliminating multiple analog-to-digital conversions, data storage, and data movement operations. Current in-sensor processing approaches rely on tunable sensors or additional weighting elements to perform linear functions such as multiply accumulate operations as the sensor acquires data. This work implements in-sensor computing with an oscillatory retinal neuron device that converts incident optical signals into voltage oscillations. A computing scheme is introduced based on the frequency shift of coupled oscillators that enables parallel, frequency multiplexed, nonlinear operations on the inputs. An experimentally implemented 3 × 3 focal plane array of coupled neurons shows that functions approximating edge detection, thresholding, and segmentation occur in parallel . An example of inference on handwritten digits from the MNIST database is also experimentally demonstrated with a 3 × 3 array of coupled neurons feeding into a single hidden layer neural network, approximating a liquid-state machine. Finally, the equivalent energy consumption to carry out image processing operations, including peripherals such as the Fourier transform circuits, is projected to be <20 fJ/OP, possibly reaching as low as 15 aJ/OP.

Objective: To explore the risk factors of neck work-related musculoskeletal disorders (WMSDs) among automobile manufacturing enterprise workers, and construct the risk prediction model. Methods: In May 2022, a cluster convenience sampling method was used to selet all front-line workers from an automobile manufacturing factory in Xiangyang City as the research objects. And a questionnaire survey was conducted using the modified Musculoskeletal Disorders Questionnaire to analyze the occurrence and exposure to risk factors of neck WMSDs. Logistic regression was used to analyze the influencing factors of workers' neck WMSDs symptoms, and Nomogram column charts was used to construct the risk prediction model. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve, the Bootstrap resampling method was used to verify the model, Hosmer-Lemeshow goodness of fit test was used to evaluate the model, and the Calibration curve was drawn. Results: A total of 1783 workers were surveyed, and the incidence of neck WMSDs symptoms was 24.8% (442/1783). Univariate logistic regression showed that age, female, smoking, working in uncomfortable postures, repetitive head movement, feeling constantly stressed at work, and completing conflicting tasks in work could increase the risk of neck WMSDs symptoms in automobile manufacturing enterprise workers ( OR =1.37, 95% CI : 1.16-1.62; OR =2.85, 95% CI : 1.56-5.20; OR =1.50, 95% CI : 1.18-1.91; OR =1.18, 95% CI : 1.02-1.37; OR =1.34, 95% CI : 1.04-1.72; OR =1.62, 95% CI : 1.21-2.17; OR =1.48, 95% CI : 1.13-1.92; P <0.05). While adequate rest time could reduce the risk of neck WMSDs symptoms ( OR =0.56, 95% CI : 0.52-0.86, P <0.05). The risk prediction model of neck WMSDs of workers in automobile manutacturing factory had good prediction efficiency, and the area under the ROC curve was 0.72 (95% CI : 0.70-0.75, P <0.001) . Conclusion: The occurrence of neck WMSDs symptoms of workers in automobile manufacturing factory is relatively high. The risk prediction model constructed in this study can play a certain auxiliary role in predicting neck WMSDs symptoms of workers in automobile manufacturing enterprise workers.

Isoquinolinone is an important heterocyclic framework in natural products and biologically active molecules, and the efficient synthesis of this structural motif has received much attention in recent years. Herein, we report a (phenyliodonio)sulfamate (PISA)-mediated, solvent-dependent synthesis of different isoquinolinone derivatives. The method provides highly chemoselective access to 3- or 4-substituted isoquinolinone derivatives by reacting o -alkenylbenzamide derivatives with PISA in either acetonitrile or wet hexafluoro-2-isopropanol., (Copyright © 2024, Hu et al.)

Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori -associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA -dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a -/- , Angptl4 -/- , and Il17a -/- Angptl4 -/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4 + T cells (T regs ) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced T reg proliferation by binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori -associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Rui Xie et al.)

Objective: Low cardiac output syndrome (LCOS) is a dangerous postoperative complication in patients with acute type A aortic dissection (ATAAD). This study aims to develop and evaluate a nomogram model that can reliably identify risk variables for postoperative LCOS in elderly patients suffering from ATAAD., Patients and Methods: In this retrospective study, a total of 310 elderly patients with ATAAD admitted to Fujian Medical University Union Hospital were included and categorized into the LCOS and non-LCOS groups. Stepwise logistic regression was used to analyze independent predictors of LCOS, and a nomogram was constructed. The best clinical decision points were found using decision analysis and a clinical impact curve., Results: Postoperative LCOS occurred in 22 (7.1%) of elderly patients with ATAAD. Independent risk factors for postoperative LCOS were age, smoking history, aortic cross-clamp (ACC), coronary heart disease (CHD), and preoperative shock. The nomogram constructed based on the identified risk factors showed good performance., Conclusions: Our results suggest that preventive treatment can be administered when needed when the risk of LCOS in older patients with ATAAD after surgery is >60%. This study contributes to developing a methodology that may improve therapeutic decision-making in older patients and provides insights for assessing the risk of LCOS.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC., Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821., Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group., Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile., Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project., Competing Interests: We declare no competing interests., (© 2024 Published by Elsevier Ltd.)

In [Mn(5-MeOsalen)(Cl)] 2 (dibenzo[24]crown-8), dibenzo[24]crown-8 formed a supramolecule via multi-point interactions with the [Mn(5-MeOsalen)(Cl)] dimer. The dimer was magnetically isolated with S T = 4 and weak interdimer magnetic interactions. The crystal exhibited single-molecule magnet behaviour with an anisotropic barrier of 26(1) K, which is the highest among the Mn-salen series reported to date.

Objective: To investigate the occurrence of low back work-related musculoskeletal disorders (WMSDs) among workers in a container manufacturing factory, and to explore the influencing factors. Methods: In June 2022, 952 workers from a container factory were selected as the research objects by cluster random sampling. Through questionnaire survey, the incidence of low back WMSDs symptoms among workers in the past one year was collected, and the influencing factors of low back WMSDs were analyzed by logistic regression. Results: The incidence rate of low back WMSDs was 46.7% (445/952). The factors with higher exposure at work were frequent slight bending (77.0%, 733/952), frequent overtime (74.1%, 705/952), and the need to turn around while working (62.3%, 593/952). Multivariate logistic regression analysis showed that age over 40 years old, smoking, drinking, often bending over slightly, sitting for a long time, maintaining a large bending posture for a long time, often working overtime, limited operating space, and there was always a need to complete conflicting things in the container manufacturing factory workers were the risks of increasing the low back WMSDs ( OR =1.68, 1.96, 2.47, 1.49, 1.84, 2.11, 1.90, 1.82, 2.00, P <0.05). Standing at work, always friendly colleagues, and always supportive and helpful leaders were protective factors for low back WMSDs ( OR =0.60, 0.32, 0.40, P <0.05) . Conclusion: The incidence of low back WMSDs symptoms in container manufacturing workers is high, and work-related factors such as frequent slight bending, long time holding large bending posture and limited operating space are the focus of ergonomic intervention in container manufacturing enterprises.

Background: Tumour vascular normalisation therapy advocates a balance between pro-angiogenic factors and anti-angiogenic factors in tumours. Artemisinin (ART), which is derived from traditional Chinese medicine, has been shown to inhibit tumour growth; however, the relationship between ART and tumour vascular normalisation in oral squamous cell carcinoma (OSCC) has not been previously reported., Methods: Different concentrations(0 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg)of ART were used to treat the xenograft nude mice model of OSCC. The effects of ART on migration and proliferation of OSCC and human umbilical vein endothelial cells (HUVEC) cells were detected by scratch assay and CCK-8 assay. OSCC cells with macrophage migration inhibitory factor (MIF) silenced were constructed to explore the effect of MIF., Results: Treatment with ART inhibited the growth and angiogenesis of OSCC xenografts in nude mice and downregulated vascular endothelial growth factor (VEGF), IL-8, and MIF expression levels. ART reduced the proliferation, migration, and tube formation of HUVEC, as well as the expression of VEGFR1 and VEGFR2. When the dose of ART was 50 mg/kg, vascular normalisation of OSCC xenografts was induced. Moreover, VEGF and IL-8 were needed in rhMIF restoring tumour growth and inhibit vascular normalisation after the addition of rhMIF to ART-treated cells., Conclusion: Artemisinin might induce vascular normalisation and inhibit tumour growth in OSCC through the MIF-signalling pathway., (© 2022 Wiley Periodicals LLC.)

Objective: Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease with a high disability rate. The clinical effect of BuShenHuoXue decoction (BSHX) for ONFH is satisfactory. We aimed to elucidate the potential angiogenic mechanisms of BSHX in a rat femoral osteonecrosis model and bone marrow mesenchymal stem cells (BMSCs)., Methods: With in vivo experiments, we established the steroid-induced osteonecrosis of the femoral head (SONFH) model using Sprague-Dawley (SD) rats (8-week-old). The rats were randomly divided into five group of 12 rats each and given the corresponding interventions: control, model (gavaged with 0.9% saline), BSHX low-, medium- and high-dose groups (0.132 3, 0.264 6, and 0.529 2 g/mL BSHX solution by gavage). After 12 weeks, haematoxylin and eosin (H&E) staining was preformed to evaluate rat osteonecrosis. the expression of angiogenic factors (CD31, VEGFA, KDR, VWF) in rat femoral head was detected by immunohistochemistry, qPCR and western blotting. In cell experiment, BMSCs were isolated and cultured in the femoral bone marrow cavity of 4-week-old SD rats. BMSCs were randomly divided into eight groups and intervened with different doses of BSHX-containing serum and glucocorticoids: control group (CG); BSHX low-, medium-, and high-dose groups (CG + 0.661 5, 1.323, and 2.646 g/kg BSHX gavage rat serum); dexamethasone (Dex) group; and Dex + BSHX low-, medium-, and high-dose groups (Dex + 0.661 5, 1.323, and 2.646 g/kg BSHX gavaged rat serum), the effects of BSHX-containing serum on the angiogenic capacity of BMSCs were examined by qPCR and Western blotting. A co-culture system of rat aortic endothelial cells (RAOECs) and BMSCs was then established. Migration and angiogenesis of RAOECs were observed using angiogenesis and transwell assay. Identification of potential targets of BSHX against ONFH was obtained using network pharmacology., Results: BSHX upregulated the expression of CD31, VEGFA, KDR, and VWF in rat femoral head samples and BMSCs (p < 0.05, vs. control group or model group). Different concentrations of BSHX-containing serum significantly ameliorated the inhibition of CD31, VEGFA, KDR and VWF expression by high concentrations of Dex. BSHX-containing serum-induced BMSCs promoted the migration and angiogenesis of RAOECs, reversed to some extent the adverse effect of Dex on microangiogenesis in RAOECs, and increased the number of microangiogenic vessels. Furthermore, we identified VEGFA, COL1A1, COL3A1, and SPP1 as important targets of BSHX against ONFH., Conclusion: BSHX upregulated the expression of angiogenic factors in the femoral head tissue of ONFH model rats and promoted the angiogenic capacity of rat RAOECs and BMSCs. This study provides an important basis for the use of BSHX for ONFH prevention and treatment., (© 2024 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Background: Limonin is one of the most abundant active ingredients of Tetradium ruticarpum . It exerts antitumor effects on several kinds of cancer cells. However, whether limonin exerts antitumor effects on colorectal cancer (CRC) cells and cancer stem-like cells (CSCs), a subpopulation responsible for a poor prognosis, is unclear., Aim: To evaluate the effects of limonin on CSCs derived from CRC cells., Methods: CSCs were collected by culturing CRC cells in serum-free medium. The cytotoxicity of limonin against CSCs and parental cells (PCs) was determined by cholecystokinin octapeptide-8 assay. The effects of limonin on stemness were detected by measuring stemness hallmarks and sphere formation ability., Results: As expected, limonin exerted inhibitory effects on CRC cell behaviors, including cell proliferation, migration, invasion, colony formation and tumor formation in soft agar. A relatively low concentration of limonin decreased the expression stemness hallmarks, including Nanog and β-catenin, the proportion of aldehyde dehydrogenase 1-positive CSCs, and the sphere formation rate, indicating that limonin inhibits stemness without presenting cytotoxicity. Additionally, limonin treatment inhibited invasion and tumor formation in soft agar and in nude mice. Moreover, limonin treatment significantly inhibited the phosphorylation of STAT3 at Y705 but not S727 and did not affect total STAT3 expression. Inhibition of Nanog and β-catenin expression and sphere formation by limonin was obviously reversed by pretreatment with 2 μmol/L colievlin., Conclusion: Taken together, these results indicate that limonin is a promising compound that targets CSCs and could be used to combat CRC recurrence and metastasis., Competing Interests: Conflict-of-interest statement: No conflicts of interest was declared., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

As an inflammatory bowel disease, ulcerative colitis (UC) does not respond well to current treatments. It is of positive clinical significance to further study the pathogenesis of UC and find new therapeutic targets. B lymphocytes play an important role in the pathogenesis of UC. The effect of anti-CD20 therapy on UC also provides new evidence for the involvement of B cells in UC process additionally, suggesting the important role and potential therapeutic value of B cells in UC. In this study, we screened the most critical immune cell-related gene modules associated with UC and found that activated B cells were closely related to the gene modules. Subsequently, key activated B cell-associated gene (BRG) signatures were obtained based on WGCNA and differential expression analysis, and three overlapping BRG-associated genes were obtained by RF and LASSO algorithms as BRG-related diagnostic biomarkers for UC. Nomogram model was further performed to evaluate the diagnostic ability of BRG-related diagnostic biomarkers, subsequently followed by UC molecular subsets identification and immunoinfiltration analysis. We also further verified the expressions of the three screened BRGs in vitro by using an LPS-induced NCM460 cell line model. Our results provide new evidence and potential intervention targets for the role of B cells in UC from a new perspective.

Background: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoimmune disease characterized by skin or osteoarticular damage. SAPHO syndrome is often misdiagnosed or missed diagnosis due to lack of overall understanding of the disease by clinicians., Purpose: To analyze the clinical symptoms and imaging features of six Han patients with SAPHO syndrome in order to provide reference for doctors to diagnose SAPHO syndrome., Material and Methods: This study retrospectively analyzed the clinical data of six Han patients with SAPHO syndrome., Results: All six Han patients with SAPHO syndrome had severe acne or pustulosis of the hands and feet, and all of them had osteoarticular damage, including five cases involving the sternoclavicular joint. Some patients showed a specific and typical "bull's head" sign on 99m Tc-labeled methylene diphosphonate bone imaging. Among the six patients recruited, there was one thoracic vertebra, one cervical vertebra, one sacroiliac joint, and one peripheral joint involvement. Two patients had limited activity due to severe osteoarticular damage., Conclusion: Due to the atypical clinical symptoms of SAPHO syndrome, most patients will experience a tortuous and long diagnostic process, while a correct understanding and timely intervention of SAPHO syndrome are essential to improve the prognosis of patients., 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.

Background: In the majority of clinical environments, the treponema pallidum particle agglutination (TPPA) test is known for its higher specificity compared to the rapid plasma reagin (RPR) test and is commonly employed for the diagnosis of syphilis, but their use for serological monitoring after syphilis therapy is controversial., Objectives: We aim to evaluate whether the TPPA titers is suitable for monitoring syphilis treatment efficacy., Methods: At first, 232 patients with primary syphilis were recruited. Serological testing was performed at baseline (initial visit) and at 6 months (±1 month) after benzathine penicillin G (BPG) treatment. Second, New Zealand white male rabbits were infected with Treponema pallidum (T. pallidum) to evaluate the changes in TPPA titers after BPG therapy. Finally, we compared the TPPA titers in the culture supernatant of rabbit splenocytes stimulated with T. pallidum with or without BPG., Results: After 6 months of treatment, 150 (64.7%) of 232 primary syphilis patients achieved serological cure, and 82 (35.3%) had adverse outcomes. Among 110 patients with TPPA titers decreased by more than fourfold, 109 of them were serological cure patients (≥4-fold decrease in RPR titers) (P ＜ 0.0001). In the rabbit model of syphilis, the TPPA titers was significantly decreased in the treatment subgroup (P = 0.016) and remained constant (±2-fold) or increased (≥4-fold) in the nontreatment subgroup. In addition, T. pallidum resulted in a positive TPPA titers in the culture supernatant of splenocytes (median titers was 1: 80), while BPG could directly reduce the TPPA titers in the culture supernatant (median titers was 1: 40) (P = 0.032)., Conclusions: A 4-fold or greater decrease in TPPA titers may indicate effective treatment in primary syphilis. Combining TPPA titers with RPR titers results may potentially aid in the early diagnosis of syphilis., 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: Sleep problems in preschoolers are becoming increasingly prominent, and the association between sleep status and anxiety symptoms has attracted growing attention. However, studies investigating the relationship between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms remain scant. We used the large sample data from the Longhua Cohort Study of Children in Shenzhen, China (LCCS) to analyze the association between bedtime and sleep in preschoolers and their anxiety symptoms., Methods: A cross-sectional study of 69,138 preschoolers in Longhua District, Shenzhen, China was conducted in 2022. Data on sociodemographic characteristics of families, bedtime, nighttime sleep duration of preschoolers, and their anxiety symptoms (measured by the Spence Preschool Children Anxiety Scale) were collected through a structured questionnaire completed by the parents. Using binary logistic regression models, the relationship between bedtime, nighttime sleep duration, and childhood anxiety symptoms was examined., Results: The bedtimes of preschoolers were concentrated between 21:01-22:00 (52.41%). Among the preschoolers, 38.70% had bedtimes later than 22:00, and 75.49% had insufficient nighttime sleep duration. The positive screening rate for anxiety symptoms among preschoolers was 3.50%. After adjusting for confounding factors using binary logistic regression models, compared with preschoolers with bedtime ≤21:00, The OR (95%CI) values of anxiety in preschoolers with bedtime ≥23:01, 22:01-23:00 and 21:01-22:00 were 2.86 (2.21-3.69), 1.51 (1.27-1.79) and 1.48 (1.26-1.76), respectively. Compared with those with sufficient nighttime sleep duration, the OR (95%CI) of children with nighttime sleep duration less than 9 h was 1.36 (1.23-1.51)., Conclusion: An association exists between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms. Preschoolers with 21:00 for bedtime and a nighttime sleep duration of 10 h may have lower anxiety symptoms. These findings support the importance of adequate sleep for preventing anxiety symptoms in children., 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 Qiu, Yin, Yang, Li, Lu, Li, Yang, Wen, Zhang, Zhang, Lei, Wang and Wu.)

Branched flows occur ubiquitously in various wave systems, when the propagating waves encounter weak correlated scattering potentials. Here we report the experimental realization of electrical tuning of the branched flow of light using a nematic liquid crystal (NLC) system. We create the physical realization of the weakly correlated disordered potentials of light via the inhomogeneous orientations of the NLC. We demonstrate that the branched flow of light can be switched on and off as well as tuned continuously through the electro-optical properties of NLC film. We further show that the branched flow can be manipulated by the polarization of the incident light due to the optical anisotropy of the NLC film. The nature of the branched flow of light is revealed via the unconventional intensity statistics and the rapid fidelity decay along the light propagation. Our study unveils an excellent platform for the tuning of the branched flow of light which creates a testbed for fundamental physics and offers a new way for steering light., (© 2024. The Author(s).)

Background: Intensive care unit-acquired weakness (ICU-AW) is a prevalent and severe issue among ICU patients. Resistance training and beta-hydroxy-beta-methylbutyrate (HMB) intervention have demonstrated the potential to enhance muscle function in patients with sarcopenia and in older adults. The purpose of this study was to determine whether resistance training and/or HMB administration would improve physical function, muscle strength, and quality of life in medical ICU patients., Methods: In this multicentre, four-arm, single-blind randomised control trial, a total of 112 adult patients with internal medical diagnoses admitted to the ICU were enrolled. These participants were then randomly assigned to one of four treatment groups: the resistance training group received protocol-based multilevel resistance exercise, the HMB group received 3 g/day of HMBCa, combination group and control groups received standard care, from the ICU to the general ward until discharge. The primary outcomes assessed at discharge included six-minute walking distance (6MWD) and short physical performance battery (SPPB). Secondary outcomes measured included muscle mass, MRC score, grip strength, and health reports quality of life at different time points. Data analysis was performed using a generalised linear mixed model, adhering to the principles of intention-to-treat analysis., Results: Resistance training and combination treatment groups exhibited significant increases in SPPB scores (3.848 and 2.832 points, respectively) compared to the control group and substantial improvements in 6WMD (99.768 and 88.577 m, respectively) (all with P < 0.01). However, no significant changes were observed in the HMB group. Muscle strength, as indicated by MRC and grip strength tests conducted at both ICU and hospital discharge, showed statistically significant improvements in the resistance training and combination groups (P < 0.05). Nevertheless, no significant differences were found between the treatment groups and usual care in terms of 60-day mortality, prevalence of ICU-AW, muscle mass, quality of life, or other functional aspects., Conclusions: Resistance training with or without beta-hydroxy-beta-methylbutyrate during the entire hospitalisation intervention improves physical function and muscle strength in medical ICU patients, but muscle mass, quality of life, and 60-day mortality were unaffected., Trial Registration: ChiCTR2200057685 was registered on March 15th, 2022., (© 2023. The Author(s).)

As a major neuron type in the brain, the excitatory neuron (EN) regulates the lifespan in C. elegans. How the EN acquires senescence, however, is unknown. Here, we show that growth differentiation factor 11 (GDF11) is predominantly expressed in the EN in the adult mouse, marmoset and human brain. In mice, selective knock-out of GDF11 in the post-mitotic EN shapes the brain ageing-related transcriptional profile, induces EN senescence and hyperexcitability, prunes their dendrites, impedes their synaptic input, impairs object recognition memory and shortens the lifespan, establishing a functional link between GDF11, brain ageing and cognition. In vitro GDF11 deletion causes cellular senescence in Neuro-2a cells. Mechanistically, GDF11 deletion induces neuronal senescence via Smad2-induced transcription of the pro-senescence factor p21. This work indicates that endogenous GDF11 acts as a brake on EN senescence and brain ageing., (© 2023. The Author(s).)

Purpose: The objective of this study was to estimate the long-term survival, late toxicity profile, and quality of life of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with combined induction chemotherapy (IC) and concurrent chemoradiotherapy from a clinical trial focused on reducing the target volume of intensity modulated radiation therapy (IMRT)., Methods and Materials: This prospective, randomized clinical trial was conducted across 6 Chinese hospitals and included 212 patients with stage III-IVB NPC who were randomly allocated to a pre-IC or post-IC group. Eligible patients were treated with 2 cycles of IC + CCRT. All patients underwent radical IMRT. Gross tumor volumes of the nasopharynx were delineated according to pre-IC and post-IC tumor extent in the pre-IC and post-IC groups, respectively., Results: After a median follow-up of 98.4 months, 32 of 97 (32.9%) and 33 of 115 (28.7%) patients experienced treatment failure or died in the pre-IC and post-IC groups, respectively. None of the patients developed grade 4 late toxicity. Late radiation-induced toxicity predominantly manifested as grade 1 to 2 subcutaneous fibrosis, hearing loss, tinnitus, and xerostomia, whereas grade 3 late toxicity included xerostomia and hearing loss. The 5-year estimated overall, progression-free, locoregional recurrence-free, and distant metastasis-free survival rates in the pre-IC and post-IC groups were 78.2% versus 83.3%, 72.0% versus 78.1%, 90.2% versus 93.5%, and 78.1% versus 82.1%, respectively. The pre-IC group had a significantly higher incidence of xerostomia and hearing damage than the post-IC group. In terms of quality of life, compared with the pre-IC group, the post-IC group showed significant improvement in cognitive function (P = .045) and symptoms including dry mouth (P = .004), sticky saliva (P = .047), and feeling ill (P = .041)., Conclusions: After long-term follow-up, we confirmed that reducing the target volumes of IMRT after IC in locoregionally advanced NPC showed no inferiority in terms of the risk of locoregional relapse and potentially improved quality of life and alleviated late toxicity., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to establish the best prediction model for postoperative nosocomial pulmonary infection through machine learning (ML) and assist physicians to make accurate diagnosis and treatment decisions., Methods: Patients with spinal cord injury (SCI) who admitted to a general hospital between July 2014 and April 2022 were included in this study. The data were segmented according to the ratio of seven to three, 70% were randomly selected to train the model, and the other 30% were used for testing. We used LASSO regression to screen the variables, and the selected variables were used in the construction of six different ML models. Shapley additive explanations and permutation importance were used to explain the output of the ML models. Finally, sensitivity, specificity, accuracy and area under receiver operating characteristic curve (AUC) were used as the evaluation index of the model., Results: A total of 870 patients were enrolled in this study, of whom 98 (11.26%) developed pulmonary infection. Seven variables were used for ML model construction and multivariate logistic regression analysis. Among these variables, age, ASIA scale and tracheotomy were found to be the independent risk factors for postoperative nosocomial pulmonary infection in SCI patients. Meanwhile, the prediction model based on RF algorithm performed best in the training and test sets. (AUC = 0.721, accuracy = 0.664, sensitivity = 0.694, specificity = 0.656)., Conclusion: Age, ASIA scale and tracheotomy were the independent risk factors of postoperative nosocomial pulmonary infection in SCI. The prediction model based on RF algorithm had the best performance., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The objectives of the study were to investigate changes in the mRNA expression levels of five genes during antral follicle development and to assess the efficacy of four timed-artificial insemination (TAI) protocols in female yaks ( Bos grunniens ). RT-qPCR analysis revealed that expression levels were greater for follicle-stimulating hormone receptor and bone morphogenic protein 15 in the small follicle, luteinizing hormone receptor, and kit ligand in the large follicle, and growth differentiation factor 9 in the medium follicle ( p  < 0.05). Non-suckling yaks were treated as a 7-d CIDR, and PGF 2α + eCG at CIDR withdrawal and TAI with frozen yak semen at 56-58 h after PGF 2α (PPe-7d); either a 7-d CIDR (PPG-7d) or a 5-d CIDR (PPG-5d), and PGF 2α at CIDR withdrawal and TAI + GnRH at 70-72 h after PGF 2α ; and GnRH treatment on Day 0, followed by PGF 2α on Day 7 and TAI + GnRH on Day 9 (GPG-7d). The results showed that the pregnancy rate (P/AI) was greater in PPG-5d than in GPG-7d ( p  < 0.05), but the P/AI was not different among the other TAI protocols. In conclusion, the expression levels of these genes in follicles are dynamically changed during antral follicle development in yaks. The PPG-5d protocol achieved a greater P/AI.

The relationships of KRAS, NRAS, BRAF and PIK3CA gene mutations with the clinicopathological features and prognosis of colorectal cancer (CRC) in patient are lacking. Furthermore, the role of ring finger protein 215 (RNF215) in CRC patients with KRAS, NRAS, BRAF and PIK3CA mutations remains unclear. In the present study, 182 surgical resection specimens from patients with primary CRC for retrospective analysis, were collected. KRAS/NRAS/BRAF/PIK3CA gene mutations were confirmed by an amplification-refractory mutation system. Immunohistochemistry (IHC) was conducted to confirm KRAS, NRAS, BRAF and PIK3CA protein expression. RNF215 expression in patients with CRC was evaluated using TIMER 2.0 database and IHC. The individual mutation rates of KRAS, NRAS, BRAF and PIK3CA were 40.7% (74/182), 4.4% (8/182), 4.4% (8/182) and 3.3% (6/182), respectively. The KRAS exon 2 mutation rate was the highest (61.5%, 64/104), and these mutations mainly occurred at codons 12 and 13. KRAS/NRAS/BRAF/PIK3CA wild-type CRC patients had significantly longer overall survival and disease-free survival than mutated KRAS/NRAS/BRAF/PIK3CA CRC patients (P<0.05). Overall, 45.4% (5/11) of patients with PIK3CA mutations had concomitant KRAS mutations. The KRAS/NRAS/BRAF/PIK3CA gene mutation rate in patients with lymph node metastasis (76.1%, 35/46) was significantly higher than that in patients without lymph node metastasis (50.8%, 69/136) (P=0.0027). There were no significant differences in IHC expression between patients with and without KRAS, NRAS, BRAF and PIK3CA mutations (P>0.05). The TIMER 2.0 analysis showed that RNF215 expression was significantly higher in the mutated BRAF group than in the wild-type BRAF group in CRC (P<0.05). In conclusion, KRAS is the most commonly mutated gene, and KRAS mutations may be a poor prognostic factor for patients with CRC. KRAS wild-type patient resistance may be related to PIK3CA gene mutations, although this needs further verification in larger cohorts. BRAF mutations may be associated with RNF215 expression in patients with CRC., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Wu et al.)

Objectives: Systemic lupus erythematosus is an autoimmune disease that involves multiple organ systems. One of its major complications, lupus nephritis (LN), is associated with a high mortality rate, and children-onset LN have a more severe course and worse prognosis than adults. Oxidative stress and inflammatory responses are involved in LN development and pathogenesis. Thus, this study aimed to explore the role of signaling regulation of the Nrf2/HMGB1/TLR/NF-κB pathway in LN pathogenesis and unravel the expression of TLR4 + CXCR4 + plasma cells subset (PCs) in LN., Methods: C57BL/6 and MRL/lpr mice were divided into four groups: control, model, vector control, and Nrf2 overexpression groups. The vector control and Nrf2 overexpression groups were injected with adenoviral vectors into the kidney in situ. Pathological changes in kidney tissues were observed by hematoxylin-eosin staining. The expression of Nrf2, HMGB1, TLR4, NF-κB, and downstream inflammatory factors in kidney samples was analyzed by quantitative polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The ratios of TLR4 + CXCR4 + PC subsets in the blood and kidneys of mice were determined by flow cytometry., Results: In MRL/lpr mice, Nrf2 was downregulated while HMGB1/TLR4/NF-κB pathway proteins were upregulated. Nrf2 overexpression decreased the expression of HMGB1, TLR4, NF-κB, and its downstream inflammatory cytokines (IL-1β and TNFα). These cytokines were negatively correlated with an increase in Nrf2 content. PC and TLR4  +  CXCR4  +  PCs in the blood and kidney samples were significantly increased in MRL/lpr mice; however, they were decreased upon Nrf2 overexpression., Conclusion: This study showed severe kidney injury in an LN mouse model and an increased ratio of TLR4  +  CXCR4  +  PCs. Furthermore, we observed that Nrf2 regulates LN immune response through the Nrf2/HMGB1/TLR4/NF-κB pathway, which can be considered an important target for LN treatment. The clinical value of the findings of our study requires further investigation., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The crystalline mechanism of the Pt 50 Au 50 alloy with grain boundary (GB) segregation during the rapid solidification process is investigated using molecular dynamics simulations. The cluster evolution and phase transformation processes during the GB segregation are analyzed by means of the energy temperature ( E - T ) curve, the pair distribution function ( g ( r )) curves, common neighborhood analysis (CNA), cluster-type index method (CTIM) and three-dimensional visualizing analyses. It is found that the GB segregation phenomenon of the Pt 50 Au 50 alloy comes from various solidification temperatures of Pt- and Au-centered clusters. Four critical temperatures T 1 (1153 K), T 2 (1073 K), T 3 (853 K) and T 4 (753 K) are discovered during the liquid-solid transition, corresponding to the supercooled liquid, Pt-centered atom nucleation, Pt-centered cluster growth, Au-centered atom nucleation and grain growth process, respectively, which is observably different to the solidification process of other alloys. The Pt atoms begin to gather together in the high-temperature liquid before the liquid-solid transition. It is also found that the CTIM proposed by us would provide an effective tool to investigate the GB segregation process.

β-hydroxybutyrate (β-HB), the most abundant ketone body, is produced primarily in the liver and acts as a substitute energy fuel to provide energy to extrahepatic tissues in the event of hypoglycemia or glycogen depletion. We now have an improved understanding of β-HB as a signal molecule and epigenetic regulatory factor as a result of intensive research over the last ten years. Because β-HB regulates various physiological and pathological processes, it may have a potential role in the treatment of metabolic diseases. The liver is the most significant metabolic organ, and the part that β-HB plays in liver disorders is receiving increasing attention. In this review, we summarize the therapeutic effects of β-HB on liver diseases and its underlying mechanisms of action. Moreover, we explore the prospects of exogenous supplements and endogenous ketosis including fasting, caloric restriction (CR), ketogenic diet (KD), and exercise as adjuvant nutritional therapies to protect the liver from damage and provide insights and strategies for exploring the treatment of various liver diseases., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

A divergent fluorination of alkylidenecyclopropanes (ACPs) and alkylidenecyclobutanes (ACBs) with selectfluor has been achieved. Four different types of products including fluorohydrins, fluoroethers, fluoroesters and fluoroketones could be prepared in moderate to excellent yields. In particular, the cyclopropanes and cyclobutanes were not destroyed during the transformations which involved a radical pathway. The applicability of this method was demonstrated by various transformations of the products.

This research aimed to investigate the effects of drinking water temperatures on growth performance, water consumption, surface temperature, organ indices, blood parameters, and intestinal development of geese, and determine the optimal drinking water temperature for 21 to 49-d geese. A total of 192 twenty-one-day male Yuzhou white geese were allocated randomly to 4 groups with 8 replicate pens per group according to the drinking water temperature (drinking water temperature [7℃-12℃] at ambient temperature [T C ], 18℃ [T 1 ], 27℃ [T 2 ], and 36℃ [T 3 ], respectively). The results showed that increasing drinking water temperature did not significantly improve the BW, ADG, and ADFI of geese (P > 0.05), whereas drinking warm water of 36℃ for geese had a trend to increase FCR (0.05 < P < 0.1). Geese in group T 2 drank the most water per day on average, whereas geese in group T C drank the least (P < 0.001). Geese in groups T 1 , T 2 , and T 3 had higher eyes temperatures than group T C (P < 0.001). No significant differences were found on the organ indices and blood biochemical parameters (P > 0.05). Geese from group T 1 had higher crypt depth and muscularis thickness of duodenum (P < 0.05), and lower ratio of villus height to crypt depth than other groups (P < 0.001). Geese from group T 1 had higher activities of trypsin in duodenum and jejuna and amylase in jejuna at 49 d than other groups (P < 0.01). Overall, these data indicate drinking water at 18℃ can increase water consumption and eyes temperature, and improve the activity of digestive enzymes and promote intestinal development. Under our experimental conditions, we recommend that the optimal drinking water temperature for geese from 21 to 49 d of age is 18°C., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

This study investigates a low-loss and flexible terahertz frequency selective surface (FSS) based on cyclic olefin copolymer (COC) film substrate, which is fabricated via a simple temperature-control method without the use of solvent. The measured frequency response of the proof-of-concept COC-based THz bandpass FSS matches well with the numerical results. Due to the ultra-low COC dielectric dissipation factor (order of 0.0001) in the THz band, the measured passband insertion loss at 559 GHz reaches 1.22 dB, which is much better than that of previously reported THz bandpass filters. This work indicates that the remarkable characteristics (small dielectric constant, low frequency dispersion, low dissipation factor, good flexibility, etc.) of the proposed COC material make it a great application prospect in the THz field.

The prognostic value of ring finger protein 215 (RNF215) in colorectal cancer (CRC) is unclear. Herein, the present study aimed to investigate the precise value of RNF215 based on CRC datasets from The Cancer Genome Atlas (TCGA) and clinical cases. CRC patient data was collected from TCGA and clinical samples from the Department of Pathology, Shanghai Fifth People's Hospital, Fudan University (Shanghai, China). Logistic regression analysis was used to investigate the correlations between RNF215 and clinicopathological characteristics. The predictive value of RNF215 for the clinical outcome of CRC was determined using Kaplan-Meier curves and Cox regression. Gene set enrichment analysis (GSEA), single-sample GSEA (ssGSEA), and angiogenesis analysis were also conducted to investigate the biological role of RNF215. Immunohistochemistry was conducted to validate the results. The results of the present study confirmed that RNF215 protein expression was significantly associated with age, lymphatic invasion, and overall survival (OS). Univariate analysis showed that upregulation of RNF215 in CRC was significantly associated with age and lymphatic invasion. Kaplan-Meier survival analysis revealed that high RNF215 expression predicted poorer OS and disease-specific survival. A total of nine experimentally detected RNF215-binding proteins were identified with the STRING tool and Cytoscape software. GSEA suggested that RNF215 was associated with several important pathways involved in tumor occurrence, including the Kyoto Encyclopedia of Genes and Genomes MAPK signaling pathway and the WikiPathway RAS signaling pathway. ssGSEA confirmed that RNF215 was significantly expressed in natural killer cells, CD8 T cells and T helper cells. Angiogenesis analysis revealed that numerous angiogenesis-related genes had the same expression trend as RNF215 in CRC. The immunostaining results indicated that RNF215 expression was significantly higher in CRC tissues than in corresponding normal tissues. In conclusion, increased RNF215 expression may be a potential molecular marker predictive of poor survival and a treatment target in CRC. In addition, RNF215 may participate in the formation of CRC through a variety of signaling pathways., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Wu et al.)

Study Design: A retrospective study., Objective: Traumatic cervical spinal cord injury (TSCI) is often associated with disc rupture. It was reported that high signal of disc and anterior longitudinal ligament (ALL) rupture on magnetic resonance imaging (MRI) were the typical signs of ruptured disc. However, for TSCI with no fracture or dislocation, there is still difficult to diagnose disc rupture. The purpose of this study was to investigate the diagnostic efficiency and localization method of different MRI features for cervical disc rupture in patient with TSCI but no any signs of fracture or dislocation., Setting: Affiliated hospital of University in Nanchang, China., Methods: Patients who had TSCI and underwent anterior cervical surgery between June 2016 and December 2021 in our hospital were included. All patients received X-ray, CT scan, and MRI examinations before surgery. MRI findings such as prevertebral hematoma, high-signal SCI, high-signal posterior ligamentous complex (PLC), were recorded. The correlation between preoperative MRI features and intraoperative findings was analyzed. Also, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these MRI features in diagnosing the disc rupture were calculated., Results: A total of 140 consecutive patients, 120 males and 20 females with an average age of 53 years were included in this study. Of these patients, 98 (134 cervical discs) were intraoperatively confirmed with cervical disc rupture, but 59.1% (58 patients) of them had no definite evidence of an injured disc on preoperative MRI (high-signal disc or ALL rupture signal). For these patients, the high-signal PLC on preoperative MRI had the highest diagnostic rate for disc rupture based on intraoperative findings, with a sensitivity of 97%, specificity of 72%, PPV of 84% and NPV of 93%. Combined high-signal SCI with high-signal PLC had higher specificity (97%) and PPV (98%), and a lower FPR (3%) and FNR (9%) for the diagnosis of disc rupture. And combination of three MRI features (prevertebral hematoma, high-signal SCI and PLC) had the highest accuracy in diagnosing traumatic disc rupture. For the localization of the ruptured disc, the level of the high-signal SCI had the highest consistency with the segment of the ruptured disc., Conclusion: MRI features, such as prevertebral hematoma, high-signal SCI and PLC, demonstrated high sensitivities for diagnosing cervical disc rupture. High-signal SCI on preoperative MRI could be used to locate the segment of ruptured disc., (© 2023. The Author(s), under exclusive licence to International Spinal Cord Society.)

Background: Unplanned reoperation is commonly performed due to postoperative complications. Previous studies have reported the incidence of unplanned reoperation following lumbar spinal surgery. But few study focused on the trend of reoperation rates, and the reasons of unplanned reoperation were not clear. In this study, we conducted a retrospective study to determine the trend of unplanned reoperation rates after degenerative lumbar spinal surgery from 2011 to 2019, and the reasons and risk factors of unplanned reoperation were also determined., Methods: Data of patients who were diagnosed with degenerative lumbar spinal disease and underwent posterior lumbar spinal fusion surgery in our institution from January 2011 to December 2019 were reviewed. Those who received unplanned reoperation during the primary admission were identified. The demographics, diagnosis, surgical segments and postoperative complications of these patients were recorded. The rates of unplanned reoperation from 2011 to 2019 were calculated, and the reasons of unplanned reoperation were statistically analysed., Results: A total of 5289 patients were reviewed. Of them, 1.91% (n = 101) received unplanned reoperation during the primary admission. The unplanned reoperation rates of degenerative lumbar spinal surgery firstly increased from 2011 to 2014, with a peak rate in 2014 (2.53%). Then, the rates decreased from 2014 to 2019, with the lowest one in 2019 (1.46%). Patients with lumbar spinal stenosis have a higher rate of unplanned reoperation (2.67%) compared with those diagnosed as lumbar disc herniation (1.50%) and lumbar spondylolisthesis (2.04%) (P < 0.05). The main reasons for unplanned reoperation were wound infection (42.57%), followed by wound hematoma (23.76%). Patients who underwent 2-segment spinal surgery had a higher unplanned reoperation rate (3.79%) than those receiving other segments surgery (P < 0.001). And different spine surgeons had different reoperation rates., Conclusions: The rates of unplanned reoperation after lumbar degenerative surgery increased at first and then decreased during past 9 years. Wound infection was the major reason for unplanned reoperation. 2-segment surgery and surgeon's surgical skills were related to the reoperation rate., (© 2023 Royal Australasian College of Surgeons.)

Changbai Mountain Nature Reserve (CNR) is a typical temperate forest ecosystem, and gross primary production (GPP) of which is closely related to topography and climate change. Research on the spatio-temporal variations and influencing factors of GPP in the CNR is of great significance for assessing growth status of vegetation and the quality of ecological environment. We calculated GPP in CNR using the vegetation photosynthesis model (VPM), and analyzed the influences of slope, altitude, temperature, precipitation, and total radiation. The results showed that the range of annual average GPP in CNR was 63-1706 g C·m -2 ·a -1 from 2000 to 2020 and that GPP decreased with the increases of altitude. Temperature played the most important role in driving the spatial varia-tion of GPP, with a significant positive correlation with GPP. During the study period, the overall annual GPP showed a significant increase trend in CNR, with an average annual increase of 13 g C·m -2 ·a -1 . The areas with increase of annual GPP accounted for 79.9% of the total area, and the area proportion of annual GPP increase differed in each plant functional type. Annual precipitation was significantly negatively correlated with GPP in 43.2% of CNR, while annual mean temperature and annual total radiation were significantly positively correlated with GPP in 47.2% and 82.4% of CNR. GPP would increase continuously in CNR under the scenario of future global warming.

Objective: The absence of proper pathogen treatment in the early stages can result in missing out on treatment chances or the overuse of antibiotics, both of which are the primary factors behind fatalities caused by lung infections. In this study, we aimed to investigate the efficacy of metagenomic next-generation sequencing (mNGS) in comparison to conventional detection methods in detecting infectious pathogens., Patients and Methods: In this retrospective study, the infection pathogens of 104 patients were examined, and 86 bronchoalveolar lavage fluid (BALF), eight pleural effusions, and ten sputum samples were collected. The conventional detection approaches and mNGS analysis were used to determine the infection pathogen profiles and their detection rates were analyzed., Results: Our study showed that mNGS was more sensitive (89.42%) than the conventional detection methods (56.73%) (p < 0.001), with a 32.69% improvement in sensitivity. The efficacy of mNGS in detecting mixed infections was significantly higher than that of conventional detection methods, with a detection rate of 85.29% compared to 17.65% (p < 0.001). The study demonstrated that mNGS had a higher sensitivity than the conventional detection methods when it came to diagnosing pulmonary infections, making it a potentially useful tool for clinical diagnosis., Conclusions: Combining mNGS with other pathogenic detection techniques can be an effective way to increase the rate of detecting pulmonary infections, as well as to provide guidance for treatment adjustments. Furthermore, the timing of sample collection and antibiotic administration can influence the effectiveness of mNGS when used on BALF specimens.

Topological defects usually emerge and vary during the phase transition of ordered systems. Their roles in thermodynamic order evolution keep being the frontier of modern condensed matter physics. Here, we study the generations of topological defects and their guidance on the order evolution during the phase transition of liquid crystals (LCs). With a given preset photopatterned alignment, two different types of topological defects are achieved depending on the thermodynamic process. Because of the memory effect of LC director field across the Nematic-Smectic (N-S) phase transition, a stable array of toric focal conic domains (TFCDs) and a frustrated one are generated in S phase, respectively. The frustrated one transfers to a metastable TFCD array with a smaller lattice constant, and further changes to a crossed-walls type N state due to the inheritance of orientational order. A free energy on temperature diagram and corresponding textures vividly describe the phase transition process and the roles of topological defects in the order evolution across the N-S phase transition. This Letter reveals the behaviors and mechanisms of topological defects on order evolution during phase transitions. It paves a way for investigating topological defect guided order evolution which is ubiquitous in soft matter and other ordered systems.

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile., (© 2022. The Author(s).)

The catalytic asymmetric cyclopropanation reaction of alkenes with diazo compounds is a direct and powerful method to construct chiral cyclopropanes that are essential to drug discovery. However, diazo compounds are potentially explosive and often require hazardous reagents for their preparation. Here, we report on the use of 1,2-dicarbonyl compounds as safe and readily available surrogates for diazo compounds in the direct catalytic asymmetric deoxygenative cyclopropanation reaction. Enabled by a class of simple and readily accessible chiral salen-Mo catalysts, the reaction proceeded with generally good enantioselectivities and yields toward a wide range of substrates (80 examples). Preliminary mechanistic studies suggested that the proposed μ-oxo bridged dinuclear Mo(III)-species was the catalytically active species. This strategy not only provides a promising route for the synthesis of chiral cyclopropanes but also opens a new window for the potential applications of chiral salen-Mo complexes in asymmetric catalysis.

Annual gross primary productivity (AGPP) is the basis for grain production and terrestrial carbon sequestration. Mapping regional AGPP from site measurements provides methodological support for analysing AGPP spatiotemporal variations thereby ensures regional food security and mitigates climate change. Based on 641 site-year eddy covariance measuring AGPP from China, we built an AGPP mapping scheme based on its formation and selected the optimal mapping way, which was conducted through analysing the predicting performances of divergent mapping tools, variable combinations, and mapping approaches in predicting observed AGPP variations. The reasonability of the selected optimal scheme was confirmed by assessing the consistency between its generating AGPP and previous products in spatiotemporal variations and total amount. Random forest regression tree explained 85 % of observed AGPP variations, outperforming other machine learning algorithms and classical statistical methods. Variable combinations containing climate, soil, and biological factors showed superior performance to other variable combinations. Mapping AGPP through predicting AGPP per leaf area (PAGPP) explained 86 % of AGPP variations, which was superior to other approaches. The optimal scheme was thus using a random forest regression tree, combining climate, soil, and biological variables, and predicting PAGPP. The optimal scheme generating AGPP of Chinese terrestrial ecosystems decreased from southeast to northwest, which was highly consistent with previous products. The interannual trend and interannual variation of our generating AGPP showed a decreasing trend from east to west and from southeast to northwest, respectively, which was consistent with data-oriented products. The mean total amount of generated AGPP was 7.03 ± 0.45 PgC yr -1 falling into the range of previous works. Considering the consistency between the generated AGPP and previous products, our optimal mapping way was suitable for mapping AGPP from site measurements. Our results provided a methodological support for mapping regional AGPP and other fluxes., 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 © 2022 Elsevier B.V. All rights reserved.)

Background: Diosgenin is a well-known steroid saponin possessing neuroprotective activities. However, it is unknown whether diosgenin could alleviate depression-like symptoms., Methods: The antidepressant-like effect of diosgenin was investigated in mice induced by chronic restraint stress. The effects of diosgenin on behaviors, inflammation, neuroendocrine, neurotrophic function, and gut microbiota were evaluated., Results: The results showed that diosgenin alleviated the depressive-like behaviors in mice. In addition, diosgenin was found to reduce serum concentrations of proinflammatory cytokines and the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Besides, diosgenin could activate hippocampal brain-derived neurotrophic factor (BDNF)/TrkB/ERK/CREB signaling pathway and improve the expression of postsynaptic protein PSD95. Meanwhile, the neurogenesis which was inhibited by chronic restraint stress, was totally reversed by diosgenin. Moreover, diosgenin increased the abundance of phylum Firmicutes and the genus Lactobacillus in stressed mice. The results further showed that diosgenin caused a strong correlation between gut microbiota composition and inflammation, the HPA axis activity, or hippocampus neurotrophic function., Limitations: Only male mice were used for evaluation in the present study, which limits the understanding of effects of diosgenin on the both sexes. In addition, the results only indicate microbiota at the phylum or genus mediate the regulation of neuroinflammation, neuroendocrine, and neurotrophic function, but does not elucidate how microbiota modulate the systems via their primary or secondary metabolites., Conclusions: The present study shows that diosgenin exerts the antidepressant activity, which is associated with the enhancement of neurotrophic function and the inhibition of inflammatory and neuroendocrine activities via the regulation of gut microbiota., Competing Interests: Conflict of Interest The authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Thoracolumbar fracture is one of the most common fractures of spine. And short-segment posterior fixation including the fractured vertebra (SSPFI) is usually used for the surgical treatment of it. However, the outcomes of SSPFI for different types of thoracolumbar fractures are not clear, and whether it is necessary to perform transpedicular bone grafting is still controversial. This study was conducted to determine the clinical efficacy of SSPFI for the treatment of different types of single-level thoracolumbar fracture, and make clear what kind of fractures need transpedicular bone grafting during the surgery., Methods: Patients with single-level thoracolumbar fracture undergoing SSPFI surgery between January 2013 and June 2020 were included in this study. The operative duration, intraoperative blood loss, anterior vertebral height ratio (AVHR) and anterior vertebral height compressive ratio (AVHC) of the fractured vertebra, local kyphotic Cobb angle (LKA), vertebral wedge angle (VWA) and correction loss during follow up period were recorded. Outcomes between unilateral and bilateral pedicle screw fixation for fractured vertebra, between SSPFI with and without transpedicular bone grafting (TBG), and among different compressive degrees of fractured vertebrae were compared, respectively., Results: A total of 161 patients were included in this study. All the patients were followed up, and the mean follow-upped duration was 25.2 ± 3.1 months (6-52 months). At the final follow-up, the AVHR was greater, and the LKA and VWA were smaller in patients with bilateral fixation (6-screw fixation) than those with unilateral fixation (5-screw fixation) of AO type A3/A4 fractures ( P  < 0.001). The correction loss of AVHR, LKA and VWA in fractured vertebra were significantly great when preoperative AVHC was >50% ( P  < 0.05). For patients with AVHC >50%, the correction loss in patients with TBG were less than those without TBG at the final follow-up ( P  < 0.05)., Conclusions: SSPFI using bilateral fixation was more effective than unilateral fixation in maintaining the fractured vertebral height for AO type A3/A4 fractures. For patients with AVHC >50%, the loss of correction was more obvious and it can be decreased by transpedicular bone grafting., 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 Luo, Liao, Sun, Wu, Zhang, Zhang, Huang, Liu, Zhang and Liu.)

A metal-free tandem reduction and N -trifluoroethylation of quinolines and quinoxalines has been developed. It provided a convenient route to access trifluoroethylated tetrahydroquinolines and tetrahydroquinoxalines. This one-pot method avoids the purification process of the intermediate. Mechanistically, the in situ -generated boryl acetal species reacted with tetrahydroquinolines to generate iminiums followed by reduction to give the target compounds.