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Zhu Zhu,1 Ping Li,2 Dongxue Chai,2 Wei Luan3 1Department of VIP Clinic, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, People’s Republic of China; 2Department of Hemodialysis Center, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, People’s Republic of China; 3Department of VIP Medical Office, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, People’s Republic of ChinaCorrespondence: Wei Luan, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160 of Pujian Road, Pudong District, Shanghai, 200127, People’s Republic of China, Tel/Fax +86 21 6838 3088, Email luanwei_2022@126.comObjective: To investigate the correlation between the frailty status of elderly patients on regular haemodialysis and the quality of life of their family caregivers.Methods: 90 elderly patients with regular haemodialysis and 90 family caregivers of the respective patients were selected from January 2020 to April 2021. The influencing factors of the caregivers’ quality of life and correlation between patient debility and caregiver quality of life were analyzed by general information questionnaire, Tilburg debility index scale, self-care ability scale, family caregiver-related quality-of-life scale and social support scale.Results: The quality of life of the family caregivers of elderly patients on regular haemodialysis is at the medium level (4.50 ± 2.96). Multiple linear stepwise regression analysis shows that the ability of patients to take care of themselves, the degree of patients’ weaknesses, whether they care for non-dialysis patients, the time to care for patients, social support and the type of current residence have significant impacts on the quality of life of the caregivers (p < 0.001). Variance analysis showed that the fitting degree of linear regression equation is relatively high, and the regression equation is significant (F = 9.195, p < 0.001, R = 0.595, R2 = 0.315). The quality of life of caregivers is positively correlated with the ability of the patients to take care of themselves, the length of care, social support and type of current residence (p < 0.05). The degree of weakness in patients is negatively correlated with taking care of non-regular dialysis patients (p < 0.05).Conclusion: The ability of patients to take care of themselves, the degree of weakness of the patients, social support and the type of current residence are the influencing factors of the burden on the family caregivers of maintenance haemodialysis patients.Keywords: maintenance haemodialysis, elderly patients, caregiver, quality of life

Yun Xia,1,&ast; Jing Guan,1,&ast; Xu Lu,2,&ast; Yifan Liu,2 Wenkang Luan2 1Department of Plastic Surgery, The People’s Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Danyang, Jiangsu, People’s Republic of China; 2Department of Plastic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Xia, Department of Plastic Surgery, The People’s Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Xinmin West Road, Danyang, Jiangsu, 212000, People’s Republic of China, Email xywindy@sina.com Wenkang Luan, Department of Plastic Surgery, Affiliated People’s Hospital of Jiangsu University, 8 Dianli Road, Zhenjiang, Jiangsu, 212000, People’s Republic of China, Email luanwenkang@126.comBackground: Long non-coding RNAs (lncRNAs) play an key role in the biological processes of various malignant tumors. SNHG16 has been confirmed to be associated with the progression of various cancers. However, function and molecular mechanism of SNHG16 in melanoma have not been studied by scholars.Methods: The expression of SNHG16 in melanoma tissues were detected by using qRT-PCR. Melanoma cases from The Cancer Genome Atlas (TCGA) and GEO#GSE15605 were included in this study. CCK-8 assay, EdU assay, transwell and scratch wound assay were used to explore the role of SNHG16 in melanoma cells. Luciferase reporter assays and RNA pull-down assay were used to explore the molecular mechanism of SNHG16 in melanoma.Results: Here, we found that SNHG16 was up-regulated in melanoma. SNHG16 enhances the growth and metastasis of melanoma. SNHG16 can promote the expression of P21-activated kinases 2 (PAK2) by sponging miR-205-5p. PAK2 is the target gene of miR-205-5p. We demonstrated that SNHG16 promotes the metastasis and growth of melanoma through miR-205-5p/PAK2 axis.Conclusion: This study firstly confirmed the role and mechanism of SNHG16 in the occurrence and development of melanoma. Therefore, SNHG16 may become a key point in the diagnosis, prognosis and treatment of melanoma patients in the future.Keywords: melanoma, growth and metastasis, SNHG16, miR-205-5p, PAK2

YeHua Liang,1 Yijia Yu,1 Weimin Luan,2 Jinghong Xu1 1Department of Plastic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of NeuroSurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Jinghong Xu, Tel/Fax +86-571-87236307, Email 1304017@zju.edu.cnAbstract: Spitz nevus (SN) is a benign melanocytic lesion with cytologic and architectural atypia. It is sometimes difficult to distinguish SNs from atypical Spitz tumor (AST), Spitz melanoma, or conventional melanoma. SNs frequently develop in Caucasians and appear on the skin of the head and lower extremities. Lesions on the ear in Asian populations are rare. Here, we report a “red Spitz tumor” on the ear of a Chinese 18-year-old boy. Dermoscopic examination revealed possibly malignant features presented as polymorphous vessels along with central white area, pseudo-network depigmentation and atypical peripheral globular pattern. The results of histopathological examination strongly suggested that the neoplasm was a compound SN and no recurrences or metastases occurred during 1-year follow-up post-surgery. Further, we review the literature on 4 previously reported cases of SN on the ear and summarize the main points of SN diagnosis and differential diagnosis with atypical Spitz tumors and melanoma.Keywords: Spitz nevus, atypical Spitz tumors, hypo-pigmented Spitz nevus, malignant melanoma

Weimin Luan,1,2,&ast; Xiqian Qi,3,&ast; Feng Liang,2 Xiaotao Zhang,2 Ziyang Jin,2 Ligen Shi,2 Benyan Luo,1 Xuejiao Dai1 1Department of Neurology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Neurology, Ningbo Municipal Hospital of T.C.M., Ningbo, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuejiao Dai; Benyan LuoDepartment of Neurology, First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, 312000, People’s Republic of ChinaTel/Fax +86-571-87235101Email x.dai@zju.edu.cn; luobenyan@zju.edu.cnPurpose: Age-related increase in myelin loss may be responsible for brain atrophy, and the mechanism is not completely understood. We aim to comprehensively delineate oligodendrocyte heterogeneity in young and aged mice and to reveal the underlying mechanism for myelin loss during aging.Methods: Diffusion tensor imaging and immunofluorescent staining were performed to verify the demyelination in the aged brains of both rodents and human. Further, the single-cell RNA sequencing data of all brain cells from young and aged mice were deeply analyzed to identify the subsets of oligodendrocyte lineage cells. Cell-to-cell interaction analysis was performed to detect the mechanism of observed changes in oligodendrocyte generation.Results: Oligodendrocytes were observed to up-regulate several senescence associated genes in aged brain. Four clusters of oligodendrocyte precursor cells (OPCs) were identified in both young and aged brains. The number of those OPCs in basal state was significantly increased, while the OPCs in the procedure of differentiation were immensely decreased in aged brain. Furthermore, it was identified that activated microglia in the aged brain released inflammatory factors to suppress OPC differentiation. Stat1 might be a potential target to transform senescent microglia into tissue repair type to promote oligodendrocyte generation.Conclusion: These results provided a perspective on how age activated microglia could impede remyelination and might give a new therapeutic target for age-related remyelinating diseases.Keywords: remyelination, oligodendrocyte precursor cells, microglia, oligodendrocytes, single cell RNA sequencing

A Master Sintering Curve (MSC) for rutile TiO2 was constructed for Pressure-less sintering using constant heating rate dilatometry data based on the combined-stage sintering model. Construction of the master sintering curve is described and the validation is proved with rutile TiO2 under different thermal histories. The concept of master sintering can be used to predict the sintering shrinkage and final density and calculate the activation energy, and a value of 105 KJ/mol for TiO2 was obtained. With one temperature dependent parameter determined experimentally, it became possible to describe accurately the densification behavior of TiO2 from the initial to final stages of sintering. .

This article, titled "Theme 04 - In Vivo Experimental Models," was published in the journal Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration. The article features a large number of authors and covers a range of topics related to in vivo experimental models. The authors explore various aspects of these models, including their use in studying amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). The article provides valuable insights into the current research and understanding of these neurodegenerative diseases. [Extracted from the article]

Y chromosome deletion and karyotype abnormalities are commonly associated with congenital non-obstructive azoospermia, impairing spermatogenesis. Specifically, the deletion of the Y chromosome Azoospermia factor a (AZFa) has been identified in infertile males with severely impaired spermatogenesis. AZFa, encompassing megabase-scale of the Y chromosome region, poses challenges in modeling AZFa deletion-related male infertility using gene editing tools. Here, we successfully created an AZFa-deleted human embryonic stem cell line utilizing the CRISPR/Cas9 gene editing tool. Our analysis indicates the AZFa-deleted stem cell line holds promise for differentiation into ectoderm, mesoderm, and endoderm, highlighting its potential for further comprehensive study.

Abstract Background In eukaryotic cells, DNA double strand breaks (DSB) are primarily repaired by canonical non-homologous end joining (c-NHEJ), homologous recombination (HR) and alternative NHEJ (alt-NHEJ). Zinc finger and SCAN domain containing 4 (ZSCAN4), sporadically expressed in 1–5% mouse embryonic stem cells (mESCs), is known to regulate genome stability by promoting HR. Results Here we show that ZSCAN4 promotes DNA repair by acting with Poly (ADP-ribose) polymerase 1 (PARP1), which is a key member of the alt-NHEJ pathway. In the presence of PARP1, ZSCAN4-expressing mESCs are associated with lower extent of endogenous or chemical induced DSB comparing to ZSCAN4-negative ones. Reduced DSBs associated with ZSCAN4 are abolished by PARP1 inhibition, achieved either through small molecule inhibitor or gene knockout in mESCs. Furthermore, PARP1 binds directly to ZSCAN4, and the second ⍺-helix and the fourth zinc finger motif of ZSCAN4 are critical for this binding. Conclusions These data reveal that PARP1 and ZSCAN4 have a protein–protein interaction, and shed light on the molecular mechanisms by which ZSCAN4 reduces DSB in mESCs.

Artemisinin is a natural sesquiterpene lactone obtained from the traditional Chinese medicinal herb Artemisia annua L. (qinghao). Artemisinin and its derivatives share an unusual endoperoxide bridge and are extensively used for malaria treatment worldwide. In addition to antimalarial activities, artemisinin and its derivatives have been reported to exhibit promising anticancer effects in recent decades. In this review, we focused on the research progress of artemisinin and its derivatives with potential anticancer activities. The pharmacological effects, potential mechanisms, and clinical trials in cancer therapy of artemisinin and its derivatives were discussed. This review may facilitate the future exploration of artemisinin and its derivatives as effective anticancer agents.

Abstract Background This project aimed to research the significance of THRIL in the diagnosis of benign and malignant solitary pulmonary nodules (SPNs) and to investigate the role of THRIL/miR-99a in malignant SPNs. Methods The study groups consisted of 169 patients with SPN and 74 healthy subjects. The differences in THRIL levels were compared between the two groups and the healthy group. The receiver operating characteristic curve (ROC) was utilized to analyze the THRIL’s significance in detecting benign and malignant SPN. Pearson correlation and binary regression coefficients represented the association between THRIL and SPN. CCK-8 assay, Transwell assay, and flow cytometry were utilized to detect the regulatory effect of THRIL silencing. The interaction between THRIL, miR-99a, and IGF1R was confirmed by the double luciferase reporter gene. Results There were differences in THRIL expression in the healthy group, benign SPN group, and malignant SPN group. High accuracy of THRIL in the diagnosis of benign SPN and malignant SPN was observed. THRIL was associated with the development of SPN. The expression of THRIL was upregulated and miR-99a was downregulated in lung cancer cells. The double luciferase report experiment confirmed the connections between THRIL/miR-99a/IGF1R. Silencing THRIL could suppress cell proliferation, migration, and invasion and promote cell apoptosis by binding miR-99a. Conclusion The detection of THRIL in serum is useful for the assessment of malignant SPN. THRIL can regulate the expression of IGF1R through miR-99a, thereby promoting the growth of lung cancer cells and inhibiting apoptosis.

MOEA/D-DE algorithm is easy to implement and widely used to deal with multi-objective optimization problems, while its hyper-parameters have a great impact on the performance of the algorithm. In this paper, based on the MOEA/D-DE algorithm framework, the Sobol global sensitivity analysis method is used to improve the cross control parameter in the differential evolution operator, and the Levy flight strategy is used to control the scale factor. Then the hyper-parameters in the MOEA/D-DE algorithm obtain adaptive ability. And MOEA/DDE algorithm with adaptive hyper-parameters (MOEA/D-DEAH) is proposed. The MOEA/D-DEAH MOEA/D-DE with different hyper-parameters settings and NSGAⅡ are tested and compared with function tests and aero-dynamic stealth optimization of airfoil. The function test results show that the new algorithm has good perfor-mance, and the algorithm can obtain strong robustness by adapting the super parameters. The optimization results of airfoil aerodynamic stealth show that MOEA/D-DEAH algorithm has better optimization results than other algo-rithms.

Abstract Four polysaccharides (MCPa, MCPb, MCPc, MCPd) were obtained from Lepidium meyenii Walp. Their structures were characterized by chemical and instrumental methods including total sugar, uronic acid and protein content determination, UV, IR and NMR spectroscopy, as well as monosaccharide composition determination and methylation analyses. Four polysaccharides were a group of glucans with different molecular weights ranging from 3.12 to 14.4 kDa, and shared a similar backbone chain consisting of (1→4)-glucose linkages with branches attached to C-3 and C-6. Furthermore, bioactivity assay showed that MCPs had concentration-dependent inhibitory activity on α-glucosidase. MCPb (Mw = 10.1 kDa) and MCPc (Mw = 5.62 kDa) with moderate molecular weights exhibited higher inhibitory activity compared with MCPa and MCPd. Graphical Abstract

The particle swarm optimization (PSO) algorithm is easy to implement and can obtain high-quality solutions to optimization problems. It is widely applied to nonlinear and difficult problems such as aerodynamic optimization. However, to solve multi-modal problems, it easily falls into locally optimal values, showing that its robustness is poor. In order to improve the robustness of the PSO algorithm, an enhanced particle swarm optimization algorithm based on parallel exchange (EPSOBPE) is proposed. The algorithm enhances the optimization capability and its robustness through the parallel evolution of the cuckoo search algorithm (CSA), PSO population, hierarchical exchange operation and reinforcement learning strategy. Therefore, the algorithm has both the global search capability of the CSA and the local capability of the PSO algorithm, thus making the EPSOBPE very robust. Functional test results show that the EPSOBPE has stronger robustness and adaptability to different problems than other intelligent optimization algorithms. Moreover, the EPSOBPE is applied to the aerodynamic optimization design of the RAE2822 airfoil and the M6 wing. Compared with other algorithms, the EPSOBPE is more robust, and its optimization capability is better.

Abstract The study had as objective to evaluate occupational hazards on grain storage unit to define a conceptual model, implemented in an algorithm to manage the grains storage facilities safety standards compliance. Sampling points location were defined for static quantification of noise, dust and heat stress hazards in grains pre-processing operations to indicate the effectiveness of the control measures implemented. Safety standards applied to grain handling and storage facilities were identified and selected. Chart flows were elaborated to the algorithm logics and conceptual modeling. The highest level of noise was present in the grain cleaning operation (99.1 dB), while the expedition operation has the highest level of dust (20.27%). The heat stress was present in the grain drying operation (43.64 WBGT). Noise analysis did not show a difference between grains, only between operations. The flow of corn grain mass caused higher dust concentrations in the expedition operation. The method applied to characterize and quantify the hazards in grain storage units was satisfactory, and it is recommended as standard, for use in corn and soybean grains handling and storage units. The algorithm to manage occupational safety at storage facilities collaborates to monitor the safety compliance on postharvest operations.