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Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease. Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease. However, transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche. Here, we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells. These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion, effectively maintaining axonal integrity in vitro. Importantly, midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts. Overall, our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.

An LSSA-BP neural network prediction model was established for more accurate onshore wind power cost prediction. Optimise the weights and thresholds of the BP neural network using the sparrow search algorithm. Comparison of the traditional BP model, GA-BP model and LSSA-BP model to verify the superiority of the LSSA-optimised BP model. Moreover, using LSSA-BP in compared with Support Vector Regression Forecasting (SVR) and Random Forest Regression Forecasting (RFR) models. The results of model trial calculations and analysis showed that the LSSA-BP model had the highest prediction accuracy and could be used as a reference for the onshore wind power cost prediction.

Large amplitude and high frequency WOB (weight on bit) fluctuation will lead to problems such as low rock breaking efficiency, short service life and slow drilling speed. This problem is particularly prominent in hard and difficult to drill formation and multi interlayer formation. The development of drilling string damping and pressurization device provides an idea for the utilization of vibration energy. Theoretically, the installation of downhole drill string absorption & hydraulic supercharging device can ensure the smooth operation of the bit. However, up to now, the influence of the characteristic parameters and application methods of downhole drill string absorption & hydraulic​ supercharging device on the WOB fluctuation at the bit is not clear. Based on the drill string dynamics experimental device, the influence of downhole drill string absorption & hydraulic supercharging device on WOB fluctuation at the bit is tested and analyzed. The results show that whether the downhole drill string absorption & hydraulic supercharging device can stabilize the bit WOB is related to its elastic stiffness, installation position, bit speed and WOB; When the WOB remains unchanged, the elastic stiffness of the elastic element of the downhole drill string absorption & hydraulic supercharging device increases, and the fluctuation range of the WOB at the bit increases; Increasing the rotating speed and increasing the WOB is conducive to controlling the WOB fluctuation of the bit. Under the condition of high rotating speed, shortening the distance between the downhole drill string absorption & hydraulic supercharging device and the bit is conducive to restraining the WOB fluctuation. The research results provide a reference for the design, development and application of damping elements of drilling string damping and pressurization device.

Based on the perspective of industrial agglomeration, this paper employs a dynamic panel model and mediating effects model to investigate the impact of digital economy’s development on air pollution in 274 Chinese cities from 2011 to 2019. The main findings include: (1) The development of the digital economy reduces air pollution emissions in Chinese cities, and the elasticity of pollution reduction is greater in central and western China than in eastern China. (2) The nexus between industrial agglomeration and air pollution is inverted-N-shaped. (3) Mechanism tests show that the digital economy can effectively promote the degree of industrial agglomeration in each area, and it plays a positive role in abating pollution in eastern and central China through the positive externalities of industrial agglomeration, but the mediating effect of industrial agglomeration on pollution reduction is not significant in western China. (4) Diversified agglomeration is an active mediator of the digital economy’s pollution reduction effect in eastern and central China. Accordingly, some policy implications are put forward for simultaneously promoting the development of the digital economy and reducing air pollution, impelling industrial agglomeration, and accelerating the green transformation in China.

High-voltage electric pulse(HVEP)drilling has become a new and efficient rock breaking method, which is also the research focus in the field of drilling speed increase. To probe into rock breaking mechanism of high voltage electric pulse, this study establishes a two-dimensional numerical model of multi-physical field coupling electric breakdown of single pair of electrodes. The model reproduces the generation of plasma channels in homogeneous red sandstone from the coupling of current field, electric breakdown field and circuit field. This paper analyzes the effect of electrode pair angle, voltage and electrode spacing on rock electrical breakdown(that is, the formation of plasma channel in rock). The model includes the circuit structure parameters of pulse tool, the occurrence and development of electrical breakdown, and the relationship between electrical breakdown intensity and time. Results indicate that the plasma channel begins to sprout from the partial area near the top of the discharge electrode and develops towards the partial weak dielectric strength. With the voltage value of loading pulse increasing gradually, the time of electrical breakdown decreases gradually; comparatively, the equivalent failure volume of rock model increases gradually, and there is a positive correlation between them. On the precondition that the rock can be electrically broken, increasing the electrode spacing can improve the rock breaking efficiency of high voltage electric pulse. The equivalent failure volume of rock shows significant fluctuations during the gradual increase of electrode inclination angle of discharge electrode, and its extreme value mostly appears in the range of electrode inclination angle of 35°~ 55°. To further promote the industrial application of high-voltage electric pulse rock breaking, this paper proposes a three-dimensional numerical model of multi-physical field coupling dynamic electric breakdown of red sandstone based on two-dimensional model, reproducing the appearance of the fracture crater in the rock during the rock breaking process with electrode bit. At the same time, the self-designed coaxial electrode bit is selected for experiments of electric breakdown, and the laboratory experimental results of electric breakdown confirm the simulation experimental results.

Weiling Zhou,1 Qian Gao,1 Lianjing Wang,2 Weijing Li,2 Cuiying He,2 Yanting Li,3 Lei Feng,1 Wei Liu,2 Lihong Liu,2 Yuan Wang1 1Department of Endocrine and Metabolic Diseases, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China; 2Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China; 3Department of Glandular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of ChinaCorrespondence: Lihong Liu, Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China, Email liulihong111222@163.com Yuan Wang, Department of Endocrine and Metabolic Diseases, The Fourth Hospital of Hebei Medical University, Shijiazhuang, HeBei Province, 050000, People’s Republic of China, Email wyuan1111122222@163.comBackground: Diffuse large B-cell lymphoma (DLBCL) involving the breast, spleen, and bone in a male patient with hepatitis B virus (HBV) infection is extremely rare in clinical practice.Case Presentation: We report a case of DLBCL involving the breast, spleen, and bone (triple expression of Bcl-2+, Bcl-6+, and 70% positive C-mcy) in a male patient with HBV admitted to our hospital. The patient was treated with EPOCH× 4, lenalidomide+EPOCH× 2 chemotherapy, intermittent methotrexate intrathecal injections to prevent central invasion, and autologous stem cell transplantation (ASCT). The patient is currently in complete remission, and the follow-up time was 43 months.Conclusion: A patient with DLBCL involving the breast, spleen, and bone can be treated with a combination of multiple regimens. If the patient’s economic conditions permit it, ASCT can be considered.Keywords: breast, viral hepatitis B, diffuse large B-cell lymphoma, triple expression, autologous stem cell transplantation

Zhen Li,1,* Bin Zhu,2,* Weiqin Chen,1 Jun Hu,1 Yingjun Xue,1 Hongmei Yin,1 Xiaobo Hu,3 Weiwei Liu1 1Department of Laboratory Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 2Department of Rehabilitation, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of China; 3General Office, Centre for Clinical Laboratory, Shanghai, 200126, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiwei Liu, Department of Laboratory Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China, Email huashanvivian@126.com Xiaobo Hu, General Office, Centre for Clinical Laboratory, Shanghai, 200126, People’s Republic of China, Email huxiaobo@vip.sina.comPurpose: The non-albicans Candida (NAC) species have recently gained great importance worldwide due to the increasing proportion in candida causing bloodstream infections. This investigation aimed to explore the efficacy of Pseudolaric acid A (PAA, a diterpenoid derived from Pseudolarix kaempferi) and its synergistic effect with fluconazole (FLC) against NAC species, including C. tropicalis, C. parapsilosis complex, and C. glabrata.Methods: The microdilution checkerboard assay and time-killing curves were performed to detect the antifungal efficiency. To examine the integrity of cell walls and membranes, calcofluor white stain and propidium iodide stain were used. The changes of intracellular ultrastructure in Candida cells after treatment were observed using transmission electron microscopy. Changes in cell viability with the autophagy inhibitor 3-MA were assessed by the XTT method.Results: It was revealed that PAA alone is effective on C. tropicalis, C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis (MIC 8– 128 μg/mL). Strong synergism against FLC-resistant C. tropicalis was observed (FICI 0.07– 0.281), when PAA and FLC were combined. PAA had dose-dependently detrimental effects on C. tropicalis cell membranes. Moreover, increased vacuoles and autophagosome formation were found in C. tropicalis exposed to PAA. And the inhibitory effect of PAA against C. tropicalis can be relieved by autophagy inhibitor 3-MA in a certain concentration range. Ultrastructural alterations of C. tropicalis were more pronounced under the combination of PAA and FLC, including separation of the cell membrane from the cell wall, increased number of vacuoles, and degradation of organelles.Conclusion: These observations indicated that PAA and its combination with FLC could be a promising therapeutic candidate for treating infections caused by NAC species.Keywords: pseudolaric acid A, fluconazole, antifungal, combination, non-albicans Candida, synergy, autophagy

Wan-Ling Liu,1– 4,* Yong-Qu Zhang,1– 5,* Xiang-Jie Luo,6 Yuan-Yuan Zhu,1– 4 Liang Song,7 Zi-He Ming,1– 4 Li-Xin Zhang,1– 4 Meng-Jun Li,1– 4 Rui-Chan Lv,8 Guo-Jun Zhang,1– 4,9,* Min Chen2– 4,* 1Department of Breast-Thyroid-Surgery and Cancer Center, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 2Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer, Xiang’an Hospital of Xiamen University, Xiamen, People’s Republic of China; 3Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, Xiamen, People’s Republic of China; 4Xiamen Research Center of Clinical Medicine in Breast & Thyroid Cancers, Xiamen, People’s Republic of China; 5Department of Breast Center, Cancer Hospital of Shantou University Medical College, Shantou, People’s Republic of China; 6College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, People’s Republic of China; 7Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences and Technology University, Xiamen, People’s Republic of China; 8Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi’an, Shanxi, People’s Republic of China; 9Cancer Research Center, School of Medicine, Xiamen University, Xiamen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min Chen; Guo-Jun Zhang, Email mchen@xah.xmu.edu.cn; gjzhang@xah.xmu.edu.cnBackground: Durable responses to immune-checkpoint blocking therapy (ICT) targeting programmed cell death protein-1/ligand-1 (PD-1/PD-L1) have improved outcomes for patients with triple negative breast cancer (TNBC). Unfortunately, only 19– 23% of patients benefit from ICT. Hence, non-invasive strategies evaluating responses to therapy and selecting patients who will benefit from ICT are critical issues for TNBC immunotherapy.Methods: We developed a novel nanoparticle-Atezolizumab (NPs-Ate) consisting of indocyanine green (ICG), gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), human serum albumin (HSA), and Atezolizumab. The efficiency of Gd-DTPA linking was verified using mass spectrometry, and the size of NPs-Ate was characterized using Nano-flow cytometry. The synthesized NPs-Ate were evaluated for fluorescence stability, penetration depth, and target specificity. TNBC cell lines and tumor-bearing mice models were used to identify the feasibility of this dual-modal second near-infrared/magnetic resonance imaging (NIR-II/MRI) system. Additionally, ICT combination with chemotherapy or radiotherapy in TNBC tumor-bearing mice models were used to assess dynamic changes of PD-L1 and predicted therapeutic responses with NPs-Ate.Results: Atezolizumab, a monoclonal antibody, was successfully labeled with ICG and Gd-DTPA to generate NPs-Ate. This demonstrated strong fluorescence signals in our NIR-II imaging system, and relaxivity (γ 1) of 9.77 mM− 1 s− 1. In tumor-bearing mice, the NIR-II imaging signal background ratio (SBR) reached its peak of 11.51 at 36 hours, while the MRI imaging SBR reached its highest as 1.95 after 12 hours of tracer injection. NPs-Ate specifically targets cells and tumors expressing PD-L1, enabling monitoring of PD-L1 status during immunotherapy. Combining therapies led to inhibited tumor growth, prolonged survival, and increased PD-L1 expression, effectively monitored using the non-invasive NPs-Ate imaging system.Conclusion: The NIR-II/MRI NPs-Ate effectively reflected PD-L1 status during immunotherapy. Real-time and non-invasive immunotherapy and response/prognosis monitoring under NIR-II/MRI imaging guidance in TNBC is a promising and innovative technology with potential for extensive clinical applications in the future.Keywords: dual-modal imaging, triple-negative breast cancer, immune-checkpoint blocking therapy, programmed cell death protein ligand-1, monitoring therapeutic response

Xiao-Bing Li, Hao Feng, Yi Dai, Wei Liu Department of Neurology, Beijing Haidian Hospital, Beijing, 100730, People’s Republic of ChinaCorrespondence: Wei Liu; Yi Dai, Department of Neurology, Beijing Haidian Hospital, No. 29 Zhongguancun Street, Haidian District, Beijing, 100730, People’s Republic of China, Tel +86– 10– 82693198 ; +86– 10– 82693192, Email liuweillma@126.com; daiyiddm8@126.comBackground: In Weber syndrome, one side of the cerebral peduncle of the midbrain is infarcted due to the occlusion of the interpeduncular branch of the posterior cerebral artery and the posterior choroidal artery, resulting in ipsilateral oculomotor nerve palsy and contralateral hemiparesis. However, Weber syndrome induced by simple anterior choroidal artery lesions has rarely been reported.Case Description: Computed tomographic angiography revealed occlusion of the left internal carotid artery in a 57-year-old male patient who was admitted to the Beijing Haidian Hospital with cerebral infarction. Thrombectomy to clear the occlusion of the left internal carotid artery and the middle cerebral artery was successfully performed in the emergency department. However, postoperative digital subtraction angiography indicated occlusion of the middle and distal segments of the left anterior choroidal artery. After recovery from anesthesia, the patient had left blepharoptosis, inability to abduct the left eye, limitation of the upward and downward gaze, left mydriasis, absence of response to light, and right hemiplegia. Complete head magnetic resonance imaging suggested left cerebral peduncle and basal ganglia infarction. Therefore, the diagnosis was that the patient had left Weber syndrome caused by a left anterior choroidal arterial embolism.Conclusion: When the anterior choroidal artery is the dominant supplier of blood to the medial region of the ipsilateral cerebral peduncle, the occlusion of this artery may lead to ipsilateral Weber syndrome.Keywords: cerebral infarction, mechanical thrombectomy, anterior choroidal artery, oculomotor nerve palsy, Weber syndrome

Wei Jia Liu,1 Laura J Taylor,2,3 Robert E MacLaren,2,3 Jasleen K Jolly4 1School of Medicine and Biomedical Sciences, University of Oxford, Oxford, UK; 2Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 3Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; 4Vision and Eye Research Institute, Anglia Ruskin University, Cambridge, UKCorrespondence: Jasleen K Jolly, Vision and Eye Research Institute, Anglia Ruskin University, Cambridge, UK, Tel/Fax +44 122 369 5034, Email jasleen.jolly@aru.ac.ukPurpose: Clinical research brings the potential of improved diagnostics, sight-saving treatments, and more accessible services to those suffering with severe sight impairment (SSI). This report investigates whether registered ophthalmology clinical studies address the leading causes of SSI in the general and working populations of the United Kingdom (UK).Methods: The latest statistics on the leading causes of SSI in the UK general and working populations were identified by searching PubMed, Cochrane Library, and TRIP databases. Clinical study registries were searched to identify registered clinical studies (on or prior to 1st December 2022) on the leading causes of SSI. The relationship between the number of clinical studies on leading causes of SSI and the percentage of SSI certifications they account for was analyzed.Results: In the UK general population, the number of registered clinical studies on the leading causes of SSI is statistically significantly correlated (Spearman’s rho = 0.86, p < 0.01) with the percentage of SSI certifications they account for. However, there is no correlation between the two in the UK working population (aged 16– 64) (Spearman’s rho = 0.15, p = 0.70). Eye conditions accounting for the most SSI certifications in individuals of working age have significantly less clinical research activity than those that cause the most SSI certifications in the general population. Out of the leading causes of SSI certifications studied, disorders of the visual cortex and congenital anomalies of the eye have the least clinical research activity.Conclusion: Clinical research into the leading causes of SSI in the general population is essential. However, it is important to consider eye conditions that cause the most severe visual impairment in individuals of working age due to the significant health and socioeconomic implications of sight loss in this population.Keywords: ophthalmology, blindness, clinical study, healthcare

Accident tolerant fuel can improve the safety of nuclear reactor core and strengthen the ability of nuclear reactor to withstand serious accidents. Coated particle dispersed fuel has become a hot research topic in accident tolerant fuel in recent years, due to its high thermal conductivity and good radiation resistance stability. Coated particle dispersed fuel consists of threedimensional isotropic coated particles as the fuel phase and silicon carbide as the matrix phase, adopting the fuel form of coated particle dispersed in the silicon carbide matrix. However, due to the low selfdiffusion rate of SiC, it is difficult to achieve high densification by solid phase sintering, which is only controlled by diffusion. The existing sintering process mainly involves adding sintering aids or generating liquid glass phase to assist in the sintering of SiC powder. Spark plasma sintering (SPS) process can activate powder particles and promote sintering, and has been widely used in nuclear ceramic sintering in recent years. This article used SPS to prepare coated particle dispersed fuel pellets, and studied the influence of sintering process parameters on the density of the coated particle dispersed fuel pellets, such as the amount of sintering additive addition, maximum sintering temperature, maximum sintering pressure, and holding time. It is found that the best process parameters for SPS sintering of coated particle dispersed fuel pellet is 7% of sintering additive addition, holding 15 minutes at 1 850 ℃ and 45 MPa. Under such process parameter, the relative density of pellet can reach 98.5% of theoretical density. In addition, the sintering mechanism of coated particle dispersed fuel was studied and it is found that the sintering of coated particle dispersed fuel can be divided into five stages. Phase detection, metallographic detection and microstructure characterization analysis of the coated particle dispersed fuel pellets were carried out. The XRD examination results indicate that after sintering, the coated particle dispersed fuel pellet is pure β phase, which indicate that SPS rapid sintering can better control the phase transition. The metallographic examination results indicate that there is no obvious contact between TRISO particles in the coated particle dispersed fuel pellet obtained under the optimal process conditions. The SEM examination results show that the overall integrity of TRISO particles is good, indicating that the structure of TRISO particles dose not break during the sintering process. In the thermal shock test, there are no penetrating micro-cracks on the surface of the fuel pellet after a thermal shock, which maintain good integrity.

Weiwei Liu,&ast; Yiru Wang,&ast; Kaizheng Chen,&ast; Min Ye, Weisha Lu, Keyu Chen, Xia Shen Department of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Shen, Department of Anesthesiology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email shenxiash@fudan.edu.cnPurpose: To examine whether intraoperative dexmedetomidine reduces postoperative delirium (POD) in elderly patients who underwent a laryngectomy.Methods: Patients were randomly assigned to receive dexmedetomidine or a saline placebo infused during surgery. The study period was July 2020 to January 2022. Participants were elderly individuals (≥ 65 years) who underwent a laryngectomy. Immediately after induction of anesthesia, a 0.5 μg.kg− 1 bolus of study solution was administered for 10 min, followed by a maintenance infusion of 0.2 μg.kg− 1.hr− 1 until the end of surgery. Patients were assessed daily for POD (primary outcome). Plasma inflammatory factors were measured at baseline, on the first postoperative day, and on the third postoperative day.Results: In total, 304 male patients were randomized; 299 patients [median (interquartile range) age, 69.0 (67.0– 73.0) years] completed in-hospital delirium assessments. There was no difference in the incidence of POD between the dexmedetomidine and control groups (21.3% [32 of 150] vs 24.2% [36 of 149], P=0.560). However, dexmedetomidine reduced POD in patients with laryngeal cancer and a higher tumor stage (21.6% vs 38.5%; OR, 0.441; 95% CI, 0.209– 0.979; P=0.039). Dexmedetomidine reduced levels of C-reactive protein (CRP) (P=0.0056) and interleukin 6 (IL-6) (P< 0.001) on the first and third postoperative days, respectively. More patients had intraoperative hypotension in the dexmedetomidine group (29.3% [44 of 150] vs 17.4% [26 of 149], P=0.015).Conclusion: Intraoperative dexmedetomidine administration did not prevent POD in patients with laryngeal cancer. Dexmedetomidine reduced serum CRP and IL-6 levels postoperatively but caused a higher occurrence of intraoperative hypotension in elderly patients after a laryngectomy.Keywords: dexmedetomidine, laryngectomy, postoperative delirium, inflammatory factors, surgery complication

Fansheng Guo,1 Xiaoye Yuan,2 Jinglin Cao,1 Xin Zhao,1 Yang Wang,1 Wenpeng Liu,1 Baowang Liu,1 Qiang Zeng1 1Department of Hepatobiliary Surgery, the Third Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 2Department of Gerontology, Hebei General Hospital, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Qiang Zeng, Department of Hepatobiliary Surgery, the Third Hospital of Hebei Medical University, No. 139, Ziqiang Road, Shijiazhuang, 050051, People’s Republic of China, Tel +86-15511308373, Email zengqiangtg@163.comBackground: Hepatocellular carcinoma (HCC) relapse is the main reason for the poor prognosis of HCC after Liver transplantation (LT). This study aimed to explore the molecular mechanisms and immune repertoire profiles of HCC relapse.Material and Methods: RNA-seq of blood samples from patients with normal (n=12) and HCC relapse (n=6) after LT was performed to identify differentially expressed genes (DEGs) and key signalling pathways. The DEGs and immune genes were further analyzed by bioinformatics. TRUST4 was used to analyze the differences in the immune repertoire between the two groups. Another 11 blood samples from patients with HCC who had received LT were collected for RT-qPCR verification of key genes.Results: A total of 131 upregulated and 157 downregulated genes were identified using RNA-seq, and GO enrichment analysis revealed that the top 15 pathways were immune-related. The PPI network identified 10 key genes. Immune infiltration analysis revealed a significant difference in the five immune cell types between the two groups. A total of 83 intersecting genes were obtained by intersecting DEGs and immune genes. 6 key genes, including MX1, ISG15, OAS1, PRF1, SPP1, and THBS1 were obtained according to the intersection of DEGs, PPI network top 10 genes and immune intersecting genes. Immune repertoire analysis showed that the usage frequency of variable (V) and joining (J) genes in the normal group was higher than that in the relapse group. RT-qPCR validation showed that the expression levels of key genes were consistent with the RNA-seq results.Conclusion: Our study identified key pathways and genes that could help determine whether transplant recipients are more prone to HCC relapse. Immune repertoire analysis revealed a difference in the usage frequency of VJ genes between the normal and relapse groups, providing a research direction for immunotherapy in patients with HCC relapse after liver transplantation.Keywords: liver transplantation, hepatocellular carcinoma relapse, RNA-sequencing, immune repertoire, variable and joining genes, V and J genes

Gut microbiota are closely related to health, and the β2-adrenergic receptor gene (ADRB2) is associated with gastrointestinal diseases. In the present study, we aimed to explore the relationship between ADRB2 gene polymorphisms and gut microbiota in Chinese Han adolescents. The relative abundance, diversity, and PICRUSt function predictions of male and female gut microbiomes differ significantly and that ADRB2 gene polymorphisms were associated with gut microbiome abundance in Chinese Han adolescents.

Wei Liu,1,&ast; Qingkun Song,2,&ast; Fang Li,1 Yu Cao,2 Ying Han,3 Jiangping Wu,2 Zhongjie Hu,4 Yonghong Zhang,5 Yingmin Ma6 1Department of Pharmacy, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Clinical Epidemiology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Center of Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Gastroenterology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Department of Hepatic Intervention, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Department of Respiratory and Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingmin Ma, Beijing Youan Hospital, Capital Medical University, Youanmen Wai 8, Fengtai District, Beijing, 100069, People’s Republic of China, Tel/Fax +86-10-83997022, Email ma.yingmin@163.comPurpose: Anti-viral and anti-inflammatory therapies were effective in altering virus repletion and immune dysregulation in Coronavirus Disease 2019 (COVID-19) patients. This study aimed to explore the effect of combination therapy on disease progression in a real-world setting.Patients and Methods: A total of 836 patients confirmed with SARS-CoV-2 infection participated in the study from 15 November to 25 December 2022 at Beijing Youan Hospital, Capital Medical University. A prospective cohort study was implemented to investigate the prognostic effect of the combination therapy on virus shedding and clinical recovery.Results: About 78% of patients used nirmatrelvir/ritonavir (N/R, Paxlovid®, Pfizer) negatively, 16% of patients were prescribed nirmatrelvir/ritonavir beyond five days of symptom onset, 4% of patients received N/R monotherapy within five days of symptom onset and 2% of patients received N/R combined with dexamethasone. Compared with untreated patients, N/R monotherapy reduced the median time to 10.0 days from 12.0 days according to the negative conversion of nucleic acid amplification test (NAAT), and combination therapy reduced the time to 7.0 days, and increased to a 1.99 (95% CI 0.92, 4.32) and 14.23-fold (95% CI 4.50, 44.95) probability of negative NAAT, respectively. N/R monotherapy reduced the clinical recovery time to 10.0 days from 13.0 days. Single-use and combined-use non-significantly increased the recovery probability by 61% and 69%, respectively. In mild and moderate patients, the HRs for clinical recovery increased to 1.69 (95% CI 0.73, 3.94) and 2.18 (95% CI 0.29, 16.62), respectively.Conclusion: Combination therapy of N/R and dexamethasone increased negative conversion of NAAT and was associated with a non-significant improvement in clinical recovery. Further studies are warranted to confirm this efficacy.Keywords: N/R, dexamethasone, negative conversion of NAAT, clinical recovery

Objective To explore the potential molecular mechanism of GluN3A gene deletion involved in depression-like behaviors. Methods Fourteen male adult GluN3A knockout (KO) mice and 15 male wild type (WT) mice were recruited in this study. Sucrose preference test (SPT) and forced swim test (FST) were conducted to measure depression-like behaviors. Then tissue samples of medial prefrontal cortex (mPFC) and hippocampus (HP) were collected from 5 mice in each group for mRNA transcriptome sequencing. Differentially expressed genes (DEGs) were screened using DESeq2 software, and some DEGs were selected and validated by qPCR. Gene Ontology (GO) enrichment analysis was performed using clusterProfiler software. Protein interaction network analysis was performed using string online database together with Cytoscape software. Results GluN3A KO mice exhibited decreased sucrose preference (P < 0.05) and sucrose consumption (P < 0.05) in FST and prolonged immobile time (P < 0.01) in FST. There were 740 and 666 DEGs found in the mPFC and the hippocampus of GluN3A KO mice, respectively. GO analysis showed that down-regulated DEGs in the mPFC were enriched in angiogenesis and neural precursor cell proliferation, while down-regulated DEGs in the hippocampus were mainly enriched in synapse assembly, axon development, dendrite development, axon guidance and synaptic membrane. And up-regulated DEGs in both mPFC and hippocampus were mainly associated with cytosolic ribosome and ribosomal subunit. Protein interaction network analysis revealed that most of the core genes in the mPFC and hippocampus were ribosomal protein genes. Conclusion GluN3A deletion may be involved in the occurrence of depression-like behaviors by regulating angiogenesis, neural precursor cell proliferation, synapse formation and protein synthesis.

The structure of antioxidants significantly affects the anti-migration and thermal-oxidative aging properties of nitrile butadiene rubber (NBR) composites, which are crucial for applications in aerospace, biomedical, and fuel cell stack sealing industries. The findings reveal that the migration rate of N-(4-anilino phenyl) maleic imide (MC), with a reactive double bond, is only 15.6%, exhibiting the best extraction resistance. 2,4,6-Tris-(N-1,4-dimethylpentyl-p-phenylenediamino)-1,3,5-triazine (TMPPD), with a greater weight and dendritic structure, follows at 47.7%, while N-isopropyl-N′-phenyl-p-phenylenediamine (4010NA) performs the worst, with 77.8%. Furthermore, after thermal-oxidative exposure, the cross-link density of NBR composites increases, generating oxygenated substances, such as ethers, aldehydes, and acids. The addition of antioxidants in the composites improves the thermal-oxidative aging properties compared to those without any antioxidants. Moreover, antioxidants 4010NA and TMPPD display superior resistance to thermal-oxidative aging properties compared to antioxidant MC.

Zhirou Xiao,1,&ast; Liping Qu,2,&ast; Haijun Chen,1 Wanting Liu,2 Yi Zhan,2 Jiahui Ling,2 Hongwei Shen,3 Ling Yang,1 Dingqiang Chen2 1Department of Laboratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Clinical Laboratory, Shenzhen Hospital of Southern Medical University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Yang, Department of Laboratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of China, Tel/Fax +86-20-83062158, Email jykresearch@126.com Dingqiang Chen, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People’s Republic of China, Tel/Fax +86-20-62783335, Email jyksys@126.comBackground: Antibiotic resistance represents a serious global health challenge, particularly with the emergence of strains resistant to last-resort antibiotics such as tigecycline, polymyxin B, and vancomycin. Urgent measures are required to alleviate this situation. To facilitate the judicious use of antibiotics, rapid and precise antimicrobial susceptibility testing (AST) is essential. Heavy water (deuterium oxide, D2O)-labeled Raman spectroscopy has emerged as a promising time-saving tool for microbiological testing.Methods: Deuterium incorporation and experimental conditions were examined to develop and apply a Raman-based AST method to evaluate the efficacy of last-resort antibiotics, including tigecycline, polymyxin B, and vancomycin, against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecium. Essential agreement and categorical agreement were used to assess the metabolism inactivation concentration based on Raman spectroscopy (R-MIC)–a new metric developed in this study—and minimum inhibitory concentration (MIC) determined via the traditional microdilution broth method. Spearman’s rank correlation coefficient was employed to measure the association between R-MIC and MIC values.Results: The Raman-based AST method achieved a 100% categorical agreement (92/92) with the traditional microdilution broth method within five hours, while the traditional method required approximately 24 h. The R-MIC values shared 68.5% (63/92) consistency with the MIC values. In addition, the R-MIC and MIC values were highly correlated (Spearman’s r=0.96), resulting in an essential agreement of 100%.Conclusion: Our optimized experimental method and conditions indicate that Raman-based AST holds great promise as a solution to overcome the time-consuming challenges of traditional AST methods.Keywords: Raman spectroscopy, tigecycline resistant, polymyxin B resistant, vancomycin resistant, antimicrobial susceptibility testing

Zhongping Duan,1 Jinling Dong,1 Ying Liu,2 Haiyang Zhou,2 Shuli Duan,2 Weihong Liu,3 Rico Liang,3 Yue Ding3 1Fourth Department of Hepatology Center, Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China; 2iGandan, the Portal for All Liver Disease Caring, Beijing, People’s Republic of China; 3Brii Biosciences Inc., Beijing, People’s Republic of ChinaCorrespondence: Rico Liang, Brii Biosciences Inc, 3F, Building 7, Zhongguancun Dongsheng International Science Park, No. 1 North. Yongtaizhuang Road, Haidian District, Beijing, 100192, People’s Republic of China, Tel/Fax +86 10 6587 6121, Email Rico.Liang@briibio.comPurpose: HBV functional cure is an optimal treatment goal for chronic hepatitis B (CHB) at present and numerous new drugs aiming for HBV functional cure are in development. We carried out an internet-based survey to understand the treatment status, unmet needs, awareness of HBV functional cure and attitude toward related clinical trials among CHB patients in China.Patients and Methods: An internet-based anonymous survey was conducted on CHB patients who reside in mainland China. Determinants of awareness and attitude were identified by logistic regression models.Results: Of the 1220 CHB patients who completed the survey questionnaire, 11.1% (135/1220) were aware of HBV functional cure and 50.2% (612/1220) answered “definitely will” to participate in related clinical trials. Participants who knew their HBsAg level (HBsAg< 1500 IU/mL: OR=3.03, 95% CI: 1.87– 4.92; HBsAg≥ 1500 IU/mL: OR=2.57, 95% CI: 1.35– 4.88), who expected to achieve HBsAg loss with treatment (OR=1.63, 95% CI: 1.07– 2.50) and who were dissatisfied with current treatment due to the failure of achieving HBsAg loss (OR=1.67, 95% CI: 1.10– 2.53) had better awareness of HBV functional cure. Participants who had HBsAg level less than 1500 IU/mL (OR=1.45, 95% CI: 1.05– 1.99), treatment with pegylated interferon alpha with or without nucleos(t)ide (OR=1.68, 95% CI: 1.11– 2.53) and better awareness of HBV functional cure (OR=1.62, 95% CI: 1.01– 2.61) were more likely to say “definitely will” to participate in related clinical trials.Conclusion: Chinese CHB patients reported a low awareness of HBV functional cure. Although CHB patients in China reported a low rate of HBV functional cure awareness, they had a high acceptance of related clinical trials.Keywords: CHB, HBV functional cure, awareness, related clinical trials

Objective To explore the effect and mechanism of zinc finger protein A20 in the nucleus pulposus cells of intervertebral disc with hypoxic conditions. Methods Rat intervertebral discs were cultured in normoxic (21% O2) and hypoxic (1% O2) conditions treated with dimethyloxalylglycine (DMOG) and divided into normoxia group, normoxia+DMOG group, hypoxia group and hypoxia+DMOG group. Histological staining and Western blotting were used to detect the histomorphological changes of the nucleus pulposus and the differences in expression of HIF-1α and A20. A20 interfering adenovirus were used to treat human nucleus pulposus cells with hypoxic and normoxic condition respectively, and divided into hypoxia+empty adenovirus group, hypoxia+A20 interference adenovirus group, normoxia+empty adenovirus group and normoxia+A20 interference adenovirus group. Flow cytometry, JC-1 detection, EdU detection and Western blotting were used to detect the differences in apoptosis, mitochondrial membrane potential, proliferation, extracellular matrix and inflammatory cytokine expression of nucleus pulposus cells. Results Compared with the normoxia group, the morphological degeneration of the other 3 groups was milder, and the protein levels of HIF-1α and A20 were significantly increased (P < 0.05); Compared with the hypoxia+empty adenovirus group, the hypoxia+A20 interference adenovirus group showed the increased protein levels of TNF-α and P-p65 in nucleus pulposus cells (P < 0.05), increased apoptosis (P < 0.05), decreased cell proliferation (P < 0.05) and decreased protein levels of extracellular matrix proteins (P < 0.05). In the normoxia+empty adenovirus group and the normoxia+A20 interference adenovirus group, there was no significant difference of the indicators mentioned above. Conclusion Hypoxia can inhibit the apoptosis and attenuate inflammation and promote the proliferation and the anabolism of extracellular matrix in nucleus pulposus cells by inducing the expression of A20 protein.

ObjectiveTo further understand the factors that promote thrombosis in essential thrombocythemia （ET） that were not included in IPSET-thrombosis （International Prognostic Score of Thrombosis for ET）. MethodsA systematic evaluation was conducted on 292 studies by retrieving PubMed，Web of Science, and The Cochrane Library. The incidence and relative risk ratio （RR） of thrombosis in ET patients with different risk factors were calculated. The confidence levels for the outcome were analyzed in combination with RR values and recommendation scores (RS) to find the thrombotic risk factors in ET patients. ResultsOut of 9 risk factors that promoted ET thrombosis, there were 4 factors in IPSET-thrombosis, including history of thrombosis （35.0%, RR=3.30, 95% CI : 2.30-4.75）, JAK2V617F positive （21.0%, RR=2.28, 95%CI : 1.14-4.56）, age over 60 years old （ 22.4% , RR=1.95, 95%CI : 1.17-3.23） and cardiovascular risk factors （17.7%, RR =1.90, 95%CI : 1.08-3.35）. The remaining five risk factors, not listed in IPSET-thrombosis, included monoclonal type of ET based on X-chromosome inactivation pattern （XCIP, 30.6%, RR=4.49, 95% CI: 1.58-12.77）, high JAK2V617F burden （33.9%, RR=3.69, 95%CI: 1.70-7.99）, leukocytosis （18.7%, RR=3.05, 95%CI: 1.81-5.13）, MPL mutation （22.1%, RR=2.40, 95%CI: 1.08-5.33） and splenomegaly （25.6%, RR=1.76, 95%CI：1.29-2.40）. ConclusionAmong the risk factors promoting thrombosis in ET patients, five thrombotic risk factors not included in the IPSET-thrombosis have been identified.

The pilots and controllers are the key roles in the air traffic control system, and the evolution rules of the control system can be obtained by analyzing the relationship between them. The control-aircraft state interdependence network is constructed according to the flight conflict among aircraft, handover relationship between control sectors, and command and monitoring relationship of aircraft. By counting the characteristics of nodes in the evolution process of the interdependence network, the changes of controller workload and aircraft flight conflict during the evolution process are analyzed. The maximum Lyapunov exponent and phase diagram analysis method are used to identify the chaos of the system. The results show that the characteristics of control sector and aircraft node can reflect the changing trend of the control system, and the evolution rules of the control system are chaotic and predictable.

Osteoclasts are the only cells responsible for bone resorption in the body, and osteoblasts are the main cells responsible for bone regeneration in the body. Under physiological conditions, these cells maintain a dynamic balance to maintain bone homeostasis. It was widely believed that the imbalance of bone metabolism is mainly affected by the expression of related inflammatory factors. However, with the gradual expansion of related studies in recent years, autophagy has been shown to be closely related to the differentiation, apoptosis and functions of osteoclasts and osteoblasts. AMP-activated protein kinase (AMPK) is an important regulator of energy metabolism in vivo and is involved in the regulation of autophagy and bone homeostasis in bone metabolism-related cells. Periodontitis is a chronic infectious disease, and its typical symptoms are alveolar bone resorption. At present, controlling the level of periodontal inflammation and alveolar bone resorption more effectively in clinical practice remains a challenge. The detection of AMPK and autophagy levels in bone metabolism-related cells shows certain prospects for the clinical prevention and treatment of periodontitis in the future. Therefore, this article reviews the regulation of periodontal inflammation levels and bone homeostasis through cell autophagy related to AMPK-mediated bone metabolism.

The green building construction is an important part of the green building, and setting up a suitable assessment model about green building construction engineering has great significance. This paper combined green construction and project management knowledge for performance assessment of green building construction engineering and used integrated method of grounded theory and G2 (G2 empowerment method) entropy method as a knowledge management strategy to build the performance assessment index set. Firstly, based on the existing literature and semi-structured interview data, grounded theory coding technology is used to identify the influencing factors of green construction performance to determine the assessment index set and corresponding assessment standards and formed the assessment index system. Then, the subjective and objective weighting methods are combined, and the G2 entropy method is used to carry out comprehensive weighting. This method has the advantages of comprehensive weighting and avoids the problem of how to allocate the proportion of subjective and objective weight in traditional comprehensive weighting. Finally, a novel knowledge management comprehensive method of performance assessment about green building construction engineering was presented. The detailed methods and steps presented in this paper can provide reference for performance assessment and knowledge management of green building construction engineering.

Zhengzhao Li,1,&ast; Lianshan Guo,1,&ast; Liqiao Lin,1 Tongting Wang,1 Yanqiu Jiang,1 Jin Song,1 Jihua Feng,1 Jianfeng Huang,2 Haoyu Li,2 Zhihao Bai,3 Wenqi Liu,4 Jianfeng Zhang1 1Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, China; 2Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, China; 3College of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, China; 4Department of Radiation Oncology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, China&ast;These authors contributed equally to this workCorrespondence: Zhihao Bai, College of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi, 530004, China, Tel/Fax +86 771-3237584, Email zhihao_bai@163.com Jianfeng Zhang, Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530007, China, Tel +86 771- 3277068, Fax +86 771- 3277277, Email zhangjianfeng@gxmu.edu.cnPurpose: Although the combined photo-thermal (PTT) and photodynamic therapy (PDT) of tumors have demonstrated promise as effective cancer therapy, the hypoxic and insufficient H2O2 supply of tumors seriously limits the efficacy of PDT, and the acidic environment reduces the catalytic activity of nanomaterial in the tumor microenvironment. To develop a platform for efficiently addressing these challenges, we constructed a nanomaterial of Aptamer@dox/GOD-MnO2-SiO2@HGNs-Fc@Ce6 (AMS) for combination tumor therapy. The treatment effects of AMS were evaluated both in vitro and in vivo.Methods: In this work, Ce6 and hemin were loaded on graphene (GO) through π-π conjugation, and Fc was connected to GO via amide bond. The HGNs-Fc@Ce6 was loaded into SiO2, and coated with dopamine. Then, MnO2 was modified on the SiO2. Finally, AS1411-aptamer@dox and GOD were fixed to gain AMS. We characterized the morphology, size, and zeta potential of AMS. The oxygen and reactive oxygen species (ROS) production properties of AMS were analyzed. The cytotoxicity of AMS was detected by MTT and calcein-AM/PI assays. The apoptosis of AMS to a tumor cell was estimated with a JC-1 probe, and the ROS level was detected with a 2’,7’-Dichlorodihydrofluorescein diacetate (DCFH-DA) probe. The anticancer efficacy in vivo was analyzed by the changes in the tumor size in different treatment groups.Results: AMS was targeted to the tumor cell and released doxorubicin. It decomposed glucose to produce H2O2 in the GOD-mediated reaction. The generated sufficient H2O2 was catalyzed by MnO2 and HGNs-Fc@Ce6 to produce O2 and free radicals (•OH), respectively. The increased oxygen content improved the hypoxic environment of the tumor and effectively reduced the resistance to PDT. The generated •OH enhanced the ROS treatment. Moreover, AMS depicted a good photo-thermal effect.Conclusion: The results revealed that AMS had an excellent enhanced therapy effect by combining synergistic PTT and PDT.Keywords: nanomaterial, photo-thermal therapy, photodynamic therapy, hypoxia

In recent years, with the rapid development of deep learning, deformable convolutional networks have received extensive attention because of their powerful feature extraction capabilities, overcoming some problems that are difficult to solve in convolutional neural networks, and have played an important role in computer vision, natural language processing and other related fields. Since there is a little research on systematic summary of the deformable convolutional network, in order to provide a detailed reference for subsequent research, this paper summarizes the related work since the introduction of the deformable convolutional network. Firstly, this paper reviews the high-quality literature in recent years, and introduces the core technologies such as deformable convolution and deformable region of interest pooling in deformable convolutional networks from the perspective of invariant features. Secondly, the collected relevant literature is classified according to different research fields, and the appli-cation of deformable convolutional networks in image recognition and classification, target detection, image seg-mentation, target tracking and other research fields is comprehensively summarized. At the same time, the perfor-mance, advantages and disadvantages of important network models are listed. Thirdly, by combing the literature, the advantages and disadvantages of the deformable convolutional network are analyzed, and the possible future research trends of the deformable convolutional network are discussed according to some problems existing at the present stage. Finally, the deformable convolutional networks are summarized and prospected based on invariant feature extraction.

Abstract To understand variations in geochemistry, organic petrology, and chemical composition of crude oil and byproducts, an immature sample from the Cretaceous Qingshankou Formation in the Songliao Basin, China, was analyzed by anhydrous and hydrous pyrolysis (AHP/HP) at a wide range of temperatures ranging from 300 °C to 450 °C. The geochemical parameters: TOC, S2, HI, and Tmax obtained from Rock–Eval pyrolysis showed both a decrease and an increase as thermal maturity progressed under HP and AHP conditions. Gas chromatography (GC) analysis showed the presence of n-alkanes in the C14 to C36 range in both expelled and residual byproducts, a Delta-shaped configuration although many samples had a gradually reducing (tapering) trend toward the high range. Gas chromatography-mass spectrometry (GC–MS) analysis revealed both an increase and a decrease in biomarker and very small changes in aromatic compound variations with increasing temperature during pyrolysis. To be more specific, C29Ts biomarker increased with temperature for the expelled byproduct, while the opposite trend was observed for the residual one. Next, The Ts/Tm ratio initially increased and then decreased with temperature while the C29H/C30H ratio fluctuated for the expelled byproduct but increased for the residual. Moreover, the GI and C30 rearranged hopane to C30 hopane ratio remained unchanged whereas the C23 tricyclic terpane/C24 tetracyclic terpane ratio and the C23/C24 tricyclic terpane ratio showed varying trends with maturity alike the C19/C23 and C20/C23 tricyclic terpane. Ultimately, based on organic petrography observations, increasing the temperature resulted in higher bitumen reflectance (%Bro, r) and optical and structural alterations in the macerals. The findings of this study provide valuable insights for future exploration endeavors in the studied region. Moreover, they contribute to our understanding of the significant role of water in the generation and expulsion of petroleum and associated byproducts, thereby facilitating the development of updated models in this field.

Yukun Feng,1,2,&ast; Na Ni,3,&ast; Wei Liu,4 Xinli Chi5,6 1Shenzhen Audencia Financial Technology Institute, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 2Faculty of Business Administration, University of Macau, Macau, People’s Republic of China; 3Faculty of Business, Lingnan University, Hong Kong, People’s Republic of China; 4School of Management, Xiamen University, Xiamen, 361005, People’s Republic of China; 5School of Psychology, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 6The Shenzhen Humanities & Social Sciences Key Research Bases of the Center for Mental Health, Shenzhen, 518060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinli Chi, School of Psychology, Shenzhen University, Shenzhen, 518060, People’s Republic of China, Tel +86 755 26976348, Email xinlichi@126.comPurpose: Past studies have indicated that air pollution is a major environmental factor that negatively affects prosocial behavior in adolescents. However, the mechanism underlying this negative relationship has not been fully explored. This study postulated that this impact may occur through individual resilience, a major psychological capital for adolescents. In addition, we studied interpersonal relations, namely, adolescents’ perceived family and teacher support, which may moderate the proposed relationship.Methods: This study combined the three-year tracking survey data of 11-to-15 old adolescents (N=1301; approximately 48% female) in China with objective data from the air quality index (AQI) to measure the level of air pollution.Results: Findings from ordinary least squares analysis indicated that air pollution negatively influences adolescents’ prosocial behavior, and their resilience mediates this negative relationship. In addition, the results showed that the negative effect of air pollution on adolescent resilience is attenuated by higher family income, whereas it is accentuated by the absence of teacher support.Conclusion: Our study provides insight into how the negative effect of air pollution on adolescents’ prosocial behavior is mediated by their psychological resilience, and highlights the moderating role of adolescents’ interpersonal relations in the association between air pollution and their psychological resilience. Our research also provides practical advice on how families, teachers, and psychologists can mitigate this negative impact.Keywords: psychological resilience, environment, interpersonal relations, prosocial behavior, adolescents, China

Baohua Li,1,2,&ast; Geng Lu,1,2 Wenbin Liu,3,&ast; Liqi Liao,2 Junfeng Ban,1,2 Zhufen Lu1 1Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2The Innovation Team for Integrating Pharmacy with Entrepreneurship, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junfeng Ban; Zhufen Lu, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 51006, People’s Republic of China, Tel +86 20 39352362, Email banjunfeng@163.com; luzhufen@163.comIntroduction: The tight structure of the blood–brain barrier severely limits the level of drug therapy for central nervous system disorders. In this study, a novel composite delivery system combining nanocarrier and microneedle technology was prepared to explore the possibility of transdermal delivery of drugs to work in the brain.Methods: Nanoparticle solutions containing paroxetine and rhodamine-B were prepared using PLGA as a carrier by the emulsification-solvent volatilization method. Then, they were mixed with hyaluronic acid and the PLGA nanoparticulate-based microneedle system (Rh-NPs-DMNs) was prepared by a multi-step decompression-free diffusion method. The particle size, zeta potential, and micromorphology of the nano solution were measured; the appearance, mechanical strength, dissolution properties, and puncture effect of the Rh-NPs-DMNs were evaluated; also, it was evaluated for in vivo live imaging properties and in vitro skin layer transport and distribution properties.Results: The mean particle size of Rh-NPs was 96.25 ± 2.26 nm; zeta potential of 15.89 ± 1.97 mV; PDI of 0.120 ± 0.079. Rh-NPs-DMNs had a high needle content of 96.11 ± 1.27% and a tip height of 651.23 ± 1.28 μm, with excellent mechanical properties (fracture force of 299.78 ± 1.74 N). H&E skin tissue staining showed that Rh-NPs-DMNs produced micron-sized mechanical pores approximately 550 μm deep immediately after drug administration, allowing for efficient circulation of the drug; and the results of in vivo imaging showed that Rh-B NPs DMNs had a faster transport rate than Rh-B DMNs, with strong fluorescent signals in both brain (P< 0.01) and hippocampus (P< 0.05) 48 h after drug administration.Conclusion: Nanoparticles can prolong blood circulation time and intracerebral retention time and have certain brain-targeting properties due to their excellent physical properties. The use of microneedle technology combined with nanocarriers provides new ideas for delivery systems for the treatment of central neurological diseases.Graphical Abstract: Keywords: soluble microneedle, PLGA nanoparticles, skin transfer, central nervous system

Abstract Traffic classification is widely used in network security and network management. Early studies have mainly focused on mapping network traffic to different unencrypted applications, but little research has been done on network traffic classification of encrypted applications, especially the underlying traffic of encrypted applications. To address the above issues, this paper proposes a network encryption traffic classification model that combines attention mechanisms and spatiotemporal features. The model firstly uses the long short-term memory (LSTM) method to analyze continuous network flows and find the temporal correlation features between these network flows. Secondly, the convolutional neural network (CNN) method is used to extract the high-order spatial features of the network flow, and then, the squeeze and excitation (SE) module is used to weight and redistribute the high-order spatial features to obtain the key spatial features of the network flow. Finally, through the above three stages of training and learning, fast classification of network flows is achieved. The main advantages of this model are as follows: (1) the mapping relationship between network flow and label is automatically constructed by the model without manual intervention and decision by network features, (2) it has strong generalization ability and can quickly adapt to different network traffic datasets, and (3) it can handle encrypted applications and their underlying traffic with high accuracy. The experimental results show that the model can be applied to classify network traffic of encrypted and unencrypted applications at the same time, especially the classification accuracy of the underlying traffic of encrypted applications is improved. In most cases, the accuracy generally exceeds 90%.

In order to evaluate the insulation condition of oil-immersed transformers effectively, a weight allocation method considering expert experience and degradation state is proposed in this paper. Firstly, a hierarchical structure for insulation condition evaluation is built based on dissolved gas in oil, ambient temperature and defect information, and subjective weights is assigned to each index based on expert experience. Then, the method of combined weight is adopted to introduce entropy weight into the weight allocation of index layer, thus weights of the index layer are dynamically adjusted to reflect the differences in the individual operation process while retaining expert experience for the criterion layer. Furthermore, the transformer insulation state is subdivided into five states from common four to realize more accurate perception of insulation state. Finally, case study of four 500 kV transformers shows that the method proposed can effectively identify normal transformers and discriminate abnormal transformers compared with the method based only on objective or subjective weight, which verifies the rationality of the method.

The southwestern Ordos Basin is located at the junction of several stable plates, where faults and fractures are relatively developed, and the influence of fractures on the distribution of tight oil reservoirs in the Yanchang Formation is not clear. To solve this problem, the characteristics of fracture development of the Yanchang Formation, southwestern Ordos Basin and its control on hydrocarbon accumulation have been systematically studied using the core, thin section, well logging, productivity, fault and sand body distribution data. The results show that vertical and horizontal bedding fractures are much more developed in the Chang 8 Member compared with the Chang 6 and 7 Members. For horizontal bedding fractures, they are mainly developed in fine sandstone, followed by siltstone, while no horizontal bedding fractures are observed in medium sandstone. This is because horizontal bedding fractures are more common in fine-grained sediments. For vertical fractures, they are also mainly developed in fine sandstone. The controlling factors of fractures include lithology, sand body thickness, sedimentary microfacies and fault–fracture coupling relationship. Fractures are well developed in the fine-grained sandstone of the wing parts of the main river channel due to small compacted space. In the area where multiple river channels intersect, the sand is pure and easy to break. Based on the comprehensive study of sedimentation, structure and fracture, the classification criteria of sweet point reservoir of the Yanchang Formation are determined: sedimentary microfacies of the main river channel and its wing, tectonic location within 1.5 km from the main fault, plane arrangement of right-lateral and right-order faults and developed fractures. The sweet point reservoir can be identified effectively using the developed sweet point screening criteria.

Metastatic diseases of the spine are becoming increasingly common with an aging population and improvements in systemic cancer therapies. Microwave and vertebroplasty are the mainstay modalities for treating painful spine metastases. Most early spinal metastases predominantly attack the adnexa, but there are few reports on its treatment. This report presents a case of a 56-year-old female who had experienced severe thoracic back pain for several days and was diagnosed with a metastatic tumor of the right transverse process of T7. Percutaneous microwave ablation in combination with bone cement injection was used to treat the metastatic tumor under CT guidance. The postoperative pain on the Visual Analogue Scale was 1/10, without nerve or vessel damage and bone cement leakage during the operation.

Xiaoling Liu, Ermei Zhong, Jinzhi Li, Chunxia Huang, Weixin Liu, Liping Zeng, Ge Song, Ronghua Jiang, Yu Liu NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Guangzhou, 510600, People’s Republic of ChinaCorrespondence: Ge Song, NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), No. 17 Mei Dong Road, Guangzhou, 510600, People’s Republic of China, Tel/Fax +86-020-87301316, Email gzdhmjyd@163.comBackground: This study aimed to explore the current situation of anxiety and depression on day of transfer in couples receiving in vitro fertilization and embryo transfer (IVF-ET) with donor sperm and analyze its influencing factors.Methods: This study selected 187 IVF-ET administered couples who received donor sperm from our Hospital from August 2021 to July 2022. On the day of IVF-ET with donor sperm transplantation, patients were investigated with general data questionnaire, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) to analyze their anxiety and depression scores and their influencing factors.Results: Scores of anxiety and depression on the day of transplantation in patients receiving IVF-ET with donor sperm were 43.98± 6.80 and 46.03± 10.61 respectively, which were higher compared to levels of Chinese health norm (P< 0.05). The anxiety score of patients’ spouses was 41.23± 6.69 and depression score was 44.23± 11.65, which were higher compared to levels of Chinese health norm (P< 0.05). Score of anxiety and depression of women was significantly higher compared to those of their spouse (P< 0.05). Anxiety and depression scores of women in non-pregnant group were significantly higher compared to those in pregnant group (P< 0.05). Regression analysis showed that education level and annual family income were influencing factors of anxiety and depression scores of IVF-ET with donor sperm couples on the day of transfer, and number of eggs taken and transfer times were influencing factors of depression scores of IVF-ET with donor sperm patients on the day of transfer.Conclusion: Psychological state of couples receiving IVF-ET with donor sperm was significantly affected, especially in female side. Medical staff should focus on patients with low education level, low family income, and more times of transfer and egg retrieval, and take targeted intervention measures to keep them in good psychological state, which is conducive to improving pregnancy outcome.Keywords: in vitro fertilization and embryo transfer with donor sperm, day of transfer, anxiety, depression, psychological state

Abstract Organoids have attracted great interest for disease modelling, drug discovery and development, and tissue growth and homeostasis investigations. However, lack of standards for quality control has become a prominent obstacle to limit their translation into clinic and other applications. “Human intestinal organoids” is the first guideline on human intestinal organoids in China, jointly drafted and agreed by the experts from the Chinese Society for Cell Biology and its branch society: the Chinese Society for Stem Cell Research. This standard specifies terms and definitions, technical requirements, test methods, inspection rules for human intestinal organoids, which is applicable to quality control during the process of manufacturing and testing of human intestinal organoids. It was originally released by the Chinese Society for Cell Biology on 24 September 2022. We hope that the publication of this standard will guide institutional establishment, acceptance and execution of proper practical protocols and accelerate the international standardization of human intestinal organoids for applications.

Abstract Background Xanthophylls are a large class of carotenoids that are found in a variety of organisms and play particularly important roles in the light-harvesting and photoprotection processes of plants and algae. Violaxanthin is an important plant-derived xanthophyll with wide potential applications in medicines, foods, and cosmetics because of its antioxidant activity and bright yellow color. To date, however, violaxanthins have not been produced using metabolically engineered microbes on a commercial scale. Metabolic engineering for microbial production of violaxanthin is hindered by inefficient synthesis pathway in the heterologous host. We systematically optimized the carotenoid chassis and improved the functional expression of key enzymes of violaxanthin biosynthesis in Escherichia coli. Results Co-overexpression of crtY (encoding lycopene β-cyclase), crtZ (encoding β-carotene 3-hydroxylase), and ZEP (encoding zeaxanthin epoxidase) had a notable impact on their functions, resulting in the accumulation of intermediate products, specifically lycopene and β-carotene. A chassis strain that did not accumulate the intermediate was optimized by several approaches. A promoter library was used to optimize the expression of crtY and crtZ. The resulting strain DZ12 produced zeaxanthin without intermediates. The expression of ZEP was further systematically optimized by using DZ12 as the chassis host. By using a low copy number plasmid and a modified dithiol/disulfide system, and by co-expressing a full electron transport chain, we generated a strain producing violaxanthin at about 25.28 ± 3.94 mg/g dry cell weight with decreased byproduct accumulation. Conclusion We developed an efficient metabolically engineered Escherichia coli strain capable of producing a large amount of violaxanthin. This is the first report of a metabolically engineered microbial platform that could be used for the commercial production of violaxanthin.

The aim of the study was to investigate the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion (IVIM) in differentiating TP53-mutant from wild type, low-risk from non-low-risk early-stage endometrial carcinoma (EC).

Abstract Intestinal cancer is one of the most frequent and lethal types of cancer. Modeling intestinal cancer using organoids has emerged in the last decade. Human intestinal cancer organoids are physiologically relevant in vitro models, which provides an unprecedented opportunity for fundamental and applied research in colorectal cancer. “Human intestinal cancer organoids” is the first set of guidelines on human intestinal organoids in China, jointly drafted and agreed by the experts from the Chinese Society for Cell Biology and its branch society: the Chinese Society for Stem Cell Research. This standard specifies terms and definitions, technical requirements, test methods for human intestinal cancer organoids, which apply to the production and quality control during the process of manufacturing and testing of human intestinal cancer organoids. It was released by the Chinese Society for Cell Biology on 24 September 2022. We hope that the publication of this standard will guide institutional establishment, acceptance and execution of proper practocal protocols, and accelerate the international standardization of human intestinal cancer organoids for clinical development and therapeutic applications.

Xin Tan, Wenjie Liu, Ying Chang, Wanmin Wu, Lichun Yang, Jiewei Liu Cataract Department, Shanxi Eye Hospital, Taiyuan, Shanxi Province, People’s Republic of ChinaCorrespondence: Jiewei Liu, Cataract Department, Shanxi Eye Hospital, Taiyuan, Shanxi Province, People’s Republic of China, Tel +86-13834648535, Email Jieweiliu1967@sina.comPurpose: The safety and stability of implantable collamer lens (ICL) implantation are closely related to the vault. We aimed to assess clinical data from patients with similar anterior segment anatomy who received ICL of the same model placed in the same position and analyze common range and factors affecting the vault inter-eye difference.Patients and Methods: A prospective study was performed, including 162 eyes of 81 patients with a bilateral ICL (V4c) implantation. Subjects were evaluated before the surgery and 1 day, 1 week, and 1 month postoperatively, and they were divided into 4 groups based on the ICL size. Bivariate correlation and multiple linear regression (stepwise) analyzed associations between vault inter-eye differences and horizontal sulcus-to-sulcus diameter, anterior chamber depth, lens thickness, ICL size, spherical equivalent, and vault.Results: One month after surgery, mean vault inter-eye differences were 74.59 ± 55.59 μm. Nearly 70% of patients presented with vault inter-eye differences lower than 100 μm. The second eye vault variance of 69% was attributed to the first eye vault. Vault inter-eye differences were positively correlated with ICL spherical equivalent (regression equation: vault inter-eye differences (μm) = 139.415 + 6.295 × ICL spherical equivalent). Vaults after ICL implantation were similar in fellow eyes, with some considerable differences. The 95% confidence interval of the vault inter-eye difference was − 34.4 ~ 183.6 μm.Conclusion: In eyes with similar anterior segment anatomy, there is a 95% probability that the vault will vary from − 34.4 μm to − 183.6 μm when a similar ICL is implanted. These results can help surgeons to select an appropriate ICL size to achieve an ideal vault. The smaller the spherical equivalent, the larger the difference between the two vaults, which provides a reference for size in moderate myopia. ICL spherical equivalent affects and predicts vault inter-eye differences after ICL implantation.Keywords: implantable collamer lens, vault, inter-eye differences

Lanlan Zong,1,&ast; Yanling Wang,1,&ast; Shiyu Song,1 Huiqi Zhang,1 Shengcai Mu,1 Wenshang Liu,1 Yu Feng,1 Shumin Wang,1 Ziwei Tu,1 Qi Yuan,1 Luhui Li,2 Xiaohui Pu1 1School of Pharmacy and Henan Province Engineering Research Center of High Value Utilization to Natural Medical Resource in Yellow River Basin, Henan University, Kaifeng, Henan, 475004, People’s Republic of China; 2Medical school, Henan Technical Institute, Kaifeng, Henan, 475004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Yuan; Xiaohui Pu, Tel/Fax +86-371-23880680, Email kaifengYQ2017@163.com; pgh425@163.comIntroduction: Hepatoma is the leading cause of death among liver diseases worldwide. Modern pharmacological studies suggest that some natural monomeric compounds have a significant effect on inhibiting tumor growth. However, poor stability and solubility, and side effects are the main factors limiting the clinical application of natural monomeric compounds.Methods: In this paper, drug-co-loaded nanoself-assemblies were selected as a delivery system to improve the chemical stability and solubility of Tanshinone II A and Glycyrrhetinic acid, and to produce a synergetic anti-hepatoma effect.Results: The study suggested that the drug co-loaded nanoself-assemblies showed high drug loading capacity, good physical and chemical stability, and controlled release. In vitro cell experiments verified that the drug-co-loaded nanoself-assemblies could increase the cellular uptake and cell inhibitory activity. In vivo studies verified that the drug co-loaded nanoself-assemblies could prolong the MRT0-∞, increase accumulation in tumor and liver tissues, and show strong synergistic anti-tumor effect and good bio-safety in H22 tumor-bearing mice.Conclusion: This work indicates that natural monomeric compounds co-loaded nanoself-assemblies would be a potential strategy for the treatment of hepatoma.Graphical Abstract: Keywords: nanoself-assemblies, drug combination, glycyrrhetinic acid, tanshinone IIA, liver cancer

Wenqin Liu, Weili Yang,&ast; Shuyan Qian&ast; DSA Center, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuyan Qian, DSA Center, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China, Email czd9571@163.comObjective: To investigate the mediating effect of self-efficacy in the relationship between social support and health literacy among young and middle-aged patients with coronary heart disease following PCI.Methods: A cross-sectional study was conducted on convenience samples of 325 young and middle-aged patients with coronary heart disease who underwent PCI within 1 to 3 months. The data were collected from the outpatient department of a tertiary general hospital in Wenzhou, China, between July 2022 and February 2023. The questionnaire format was utilized to gather data on demographic characteristics, social support, self-efficacy, and health literacy. A structural equation model was employed to establish and validate the pathways.Results: The mean age of the patients included in the study was 45.32 years old, while their levels of health literacy, self-efficacy, and social support were 64.12± 7.45, 27.71± 4.23, and 65.53± 6.43 respectively. Significant associations were observed between social support and health literacy in the CHD population, with self-efficacy playing a partial mediating role. Together, social support and self-efficacy accounted for 53.3% of the variance in health literacy. The Pearson correlation analysis revealed a significant positive association between health literacy and both social support (r = 0.390, P < 0.01) and self-efficacy (r = 0.471, P < 0.01).Conclusion: Social support exerted a direct impact on health literacy and an indirect effect on health literacy through self-efficacy among patients with CHD.Keywords: social support, self-efficacy, health literacy, young and middle-aged patients, coronary heart disease, structural equation modelling

Terahertz (THz) wave plays important roles in the research of material properties, the non-invasive human security check and the next generation wireless communication. The progress of the scientific and technological applications of THz wave is strongly dependent on the improvement of THz detectors. Here a novel THz wave detection scheme is proposed in which the THz radiation is detected by an audible microphone based on the photo-thermo-acoustic (PTA) effect in graphene foam. Thanks to the room-temperature broadband electromagnetic absorption characteristics of graphene foam and the fast heat transfer between graphene foam and ambient air, this detection method not only inherits the advantages of the photo-thermal THz detector such as room-temperature and full bandwidth, but also has a response time 3 orders of magnitude faster than the photo-thermal detector. Besides, no micro-antenna/electrode is required to fabricate in the graphene foam THz detector which greatly simplifies the detector design and decreases the fabrication cost. It concludes that the room-temperature, full-bandwidth, fast-speed (≥10 kHz), and easy-to-fabricate THz detector developed in this work has superior comprehensive performances among both the commercial THz detectors and the detectors recently developed in laboratory.

Periodontal diseases are chronic diseases of oral cavity comprising of inflammatory conditions which effect the supporting structures of dentition. It is a multifactorial disease which is also known to be affected by genetic and environmental factors. However, some of the clinical parameters such as probing depth, attachment level, plaque index, bleeding on probing and radiographic assessment of alveolar bone are known to assess the severity of disease, although the disease activity is not measured. In the current scenario the salivary diagnostic markers for diagnosis of periodontal diseases have included the salivary enzymes, immunoglobulins, bacterial components or products, phenotypic markers such as epithelial markers. Also, saliva is a mirror of oral and systemic health and a valuable source to find out the physiological aspects of periodontal diseases. The present review thus highlights various salivary biomarkers which are quick, easy and reliable method for assessing and monitoring periodontal disease that improves and speeds treatment decisions and moves the field closer to individualized point-of-care diagnostics.

In order to establish a method for quantitative analysis of the purity of gaseous Uranium hexafluoride using Fourier infrared spectroscopy under low pressure, the absorption peak at 1 150 cm-1 was selected as the characteristic absorption peak for quantitative analysis of the purity of uranium hexafluoride. It was showed that the pressure of gas analysis has a direct effect on the area of characteristic peak under low pressure condition, which could not be ignored in the process of purity calculation. Aiming at the online analysis demand of the residual UF6 in the tail material after UF6 gas was purified, the gas standard UF6 samples with different purity and pressure conditions were analyzed by establishing an infrared analysis system, a standard sample ratio system and a background spectrum calibration device that could meet the requirements of vacuum sealing. The calculation formula for the relationship between the UF6 purity and its characteristic absorption peak area as well as the gas absolute pressure were established. The experimental results showed that the purity of gaseous UF6 which was in the pressure range of 60~140 Pa and the purity range of 0~100% could be accurately analyzed by this method.

Jifen Hu,1,2,&ast; Jian Gao,1,2,&ast; Chunlin Wang,1,2,&ast; Wuling Liu,1,2 Anling Hu,1,2 Xiao Xiao,1,2 Yi Kuang,1,2 Kunlin Yu,1,2 Babu Gajendran,1– 3 Eldad Zacksenhaus,4 Weidong Pan,1,2 Yaacov Ben-David1,2 1State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou, 550014, People’s Republic of China; 2The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, Guizhou, People’s Republic of China; 3School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, Guizhou Province, 550025, People’s Republic of China; 4Department of Medicine, University of Toronto, Toronto, Ontario, Canada, and Division of Advanced Diagnostics, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada&ast;These authors contributed equally to this workCorrespondence: Yaacov Ben-David, State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Province Science City, High Tech Zone, Baiyun District, Guiyang, 550014, People’s Republic of China, Email yaacovbendavid@hotmail.comAim: Histamine decarboxylase (HDC) catalyzes decarboxylation of histidine to generate histamine. This enzyme affects several biological processes including inflammation, allergy, asthma, and cancer, although the underlying mechanism is not fully understood. The present study provides a novel insight into the relationship between the transcription factor FLI1 and its downstream target HDC, and their effects on inflammation and leukemia progression.Methods: Promoter analysis combined with chromatin immunoprecipitation (ChIp) was used to demonstrate binding of FLI1 to the promoter of HDC in leukemic cells. Western blotting and RT-qPCR were used to determine expression of HDC and allergy response genes, and lentivirus shRNA was used to knock-down target genes. Proliferation, cell cycle, apoptosis assays and molecular docking were used to determine the effect of HDC inhibitors in culture. An animal model of leukemia was employed to test the effect of HDC inhibitory compounds in vivo.Results: Results presented herein demonstrate that FLI1 transcriptionally regulates HDC by direct binding to its promoter. Using genetic and pharmacological inhibition of HDC, or the addition of histamine, the enzymatic product of HDC, we show neither have a discernable effect on leukemic cell proliferation in culture. However, HDC controls several inflammatory genes including IL1B and CXCR2 that may influence leukemia progression in vivo through the tumor microenvironment. Indeed, diacerein, an IL1B inhibitor, strongly blocked Fli-1-induced leukemia in mice. In addition to allergy, FLI1 is shown to regulate genes associated with asthma such as IL1B, CPA3 and CXCR2. Toward treatment of these inflammatory conditions, epigallocatechin (EGC), a tea polyphenolic compound, is found strongly inhibit HDC independently of FLI1 and its downstream effector GATA2. Moreover, the HDC inhibitor, tetrandrine, suppressed HDC transcription by directly binding to and inhibiting the FLI1 DNA binding domain, and like other FLI1 inhibitors, tetrandrine strongly suppressed cell proliferation in culture and leukemia progression in vivo.Conclusion: These results suggest a role for the transcription factor FLI1 in inflammation signaling and leukemia progression through HDC and point to the HDC pathway as potential therapeutics for FLI1-driven leukemia.Graphical Abstract: Keywords: HDC, histamine, FLI1, inflammation, allergy, asthma, leukemia progression

Objective: To explore whether Cyclic Adenosine Monophosphate (cAMP)-Epac1 signaling is activated in 1-Desamino-8-D-arginine-Vasopressin-induced Endolymphatic Hydrops (DDAVP-induced EH) and to provide new insight for further in-depth study of DDAVP-induced EH. Methods: Eighteen healthy, red-eyed guinea pigs (36 ears) weighing 200–350 g were randomly divided into three groups: the control group, which received intraperitoneal injection of sterile saline (same volume as that in the other two groups) for 7 consecutive days; the DDAVP-7d group, which received intraperitoneal injection of 10 mg/mL/kg DDAVP for 7 consecutive days; and the DDAVP-14d group, which received intraperitoneal injection of 10 μg/mL/kg DDAVP for 14 consecutive days. After successful modeling, all animals were sacrificed, and cochlea tissues were collected to detect the mRNA and protein expression of the exchange protein directly activated by cAMP-1 and 2 (Epac1, Epac2), and Repressor Activator Protein-1 (Rap1) by Reverse Transcription (RT)-PCR and western blotting, respectively. Results: Compared to the control group, the relative mRNA expression of Epac1, Epac2, Rap1A, and Rap1B in the cochlea tissue of the DDAVP-7d group was significantly higher (p

Wen Ting Zhu,1,&ast; Xiang Feng Zeng,2,&ast; Hua Yang,2 Meng Lei Jia,1 Wei Zhang,2 Wei Liu,2 Sheng Yao Liu3 1Department of Pharmacy, Biomedicine Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, People’s Republic of China; 2Department of Orthopedics, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China; 3Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Liu, Department of Orthopedics, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China, Email lwsurgery@163.com Sheng Yao Liu, Department of Orthopedics, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, People’s Republic of China, Email liushengyao12@163.comBackground: Osteosarcoma is a malignant bone tumor with a high rate of lung metastasis and mortality. It has been demonstrated that resveratrol can inhibit tumor proliferation and metastasis, but its application is limited due to poor water solubility and low bioavailability. In this study, we proposed to prepare folate-modified liposomes loaded with resveratrol to investigate its anti-osteosarcoma effect in vitro and in vivo.Methods: We prepared and characterized resveratrol liposomes modified with folate (denoted as, FA-Res/Lps). The effects of FA-Res/Lps on human osteosarcoma cell 143B proliferation, apoptosis, and migration were investigated by MTT, cell cloning, wound-healing assay, transwell, and flow cytometry. A xenograft tumor and lung metastasis model of osteosarcoma was constructed to study the therapeutic effects of FA-Res/Lps on the growth and metastasis of osteosarcoma in vivo.Results: The FA-Res/Lps were prepared with a particle size of 118.5 ± 0.71 and a small dispersion coefficient of 0.154 ± 0.005. We found that FA-modified liposomes significantly increased resveratrol uptake by osteosarcoma cells 143B in flow cytometric assay, resulting in FA-Res/Lps, which inhibit tumor proliferation, migration and induce apoptosis more effectively than free Res and Res/Lps. The mechanism of action may be associated with the inhibition of JAK2/STAT3 signaling. In vivo imaging demonstrated that FA-modified DiR-modified liposomes significantly increased the distribution of drugs at the tumor site, leading to significant inhibition of osteosarcoma growth and metastasis by FA-Res/Lps. Furthermore, we found that FA-Res/Lps did not cause any adverse effects on mice body weight, liver, or kidney tissues.Conclusion: Taken together, the anti-osteosarcoma effect of resveratrol is significantly enhanced when it is loaded into FA-modified liposomes. FA-Res/Lps is a promising strategy for the treatment of osteosarcoma.Keywords: resveratrol, liposomes, osteosarcoma, lung metastasis, JAK2/STAT3 pathway

SiC whisker was added into SiBCN ceramics obtained by pyrolysis of polyborosilazane (PSNB) by ultrasonic combined with ball milling. The effects of different mass fractions SiC whisker on the density, hardness, bending strength and microstructure of SiBCN ceramic matrix composites were studied. The results show that with the mass fraction of SiC whisker increasing from 0% to 25%, the density of the composite is first decreased and finally increased, the porosity is gradually increased, the hardness is gradually decreased, and the bending strength is first increased, then decreased and finally increased; It was found that the three-point bending strength of SiCw/SiBCN composite with 5% SiC whisker can reach 191 MPa, which is 218% higher than that of pure SiBCN matrix without whisker (60 MPa). XRD analysis shows that the introduction of whiskers has little effect on the phase composition of sintered composites; by observing the micro morphology of the fracture surface of the materials, it was found that the existence modes of whiskers in the matrix mainly include bridging and agglomeration bridging. Bridging whiskers are conducive to strengthening the material, while agglomerated whiskers will form pores in the matrix, so as to reduce the strength of the material.

The VSR-VSI dual three-phase pulse width modulation (PWM) converters based on the cascade connection of a front-end three-phase voltage source rectifier (VSR) and a back-end three-phase voltage source inverter (VSI) have been widely used in elevator energy feedback systems, but the front-end three-phase VSR using the traditional proportional integral (PI) double closed-loop control structure usually has the problem that the mid-end DC voltage cannot take into account the disturbance immunity and the follow-ability. Given this, an improved DC voltage regulation strategy of the three-phase PWM rectifier based on two-degree-of-freedom proportional integral differential (PID) is proposed. Firstly, the structure and working principle of the three-phase VSR-VSI dual three-phase PWM converters are expounded. Then, the PI double closed-loop control scheme of the front-end three-phase VSR and its parameter design process are given to analyze the reasons why this traditional scheme cannot have good disturbance immunity and follow-ability of the DC voltage regulation system. On this basis, an optimized DC voltage regulation improvement strategy for the front-end three-phase VSR based on two-degree-of-freedom PID and its corresponding parameter design method are given. Finally, the correctness and the superiority of the proposed three-phase PWM-VSR DC voltage regulation strategy are verified by using the simulation and experimental comparison results.