bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression analysis of cytokines IL-5, IL-6, IL-8, IL-17 and VEGF in breast cancer patients
Authors: Liu Gang , Chen Xiang-Ting , Zhang Hao , Chen Xin
Published: December 2022

Objective

To investigate the relationship between changes in peripheral blood vascular endothelial growth factor (VEGF), interleukin-5 (IL-5), interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-17 (IL-17) concentrations in breast cancer patients and their significance and clinical value in breast cancer staging and invasive metastasis.

Methods

From September 2021 to April 2022, 60 breast cancer patients from Chongqing Medical University Hospital No. 2022 were enrolled in the breast breast cancer surgery group, while 30 patients with benign breast disease were enrolled in the control group during the same period. Venous blood samples were collected at admission and 1 week after surgery to determine the expression of these factors in serum. Statistical methods such as Wilcoxon test and Spearman correlation analysis were used to analyze the relationship between the above factors and the clinicopathological characteristics of the patients.

Results

By analyzing data from patients with benign and malignant breast tumors, an association was found with serum levels of IL-6, IL-17 and VEGF. Their respective areas under the operating characteristic curve were 0.649, 0.734 and 0.656 (P < 0.05). There were significant differences in the cytokine expression levels of IL-17 and VEGF in different molecular typing (P values were 0.008 and 0.040, respectively). The expression levels of IL-17 and VEGF were higher in HER-2 receptor-positive and triple-negative patients than in hormone receptor-positive patients (P < 0.05). Also, no significant correlation was found between the various cytokines mentioned in the article and breast cancer lymph node metastasis and Tumor Node Metastasis stage (TNM stage). In addition, in the breast cancer surgery group, postoperative VEGF levels were lower (P < 0.05) and IL-6 levels were higher (P < 0.05) compared to preoperative levels.

Conclusions

Serum IL-6, IL-17, and VEGF are strongly associated with breast cancer development and can be used as a reference indicators for breast cancer diagnosis. In addition, post-operative VEGF levels decreases and IL-6 levels increases compared to pre-operative levels, which can also be used as an a postoperative follow-up indicator. In contrast, IL-5 and IL-8 have not found to be significantly associated with breast cancer patients in this study, which requires further study.
Microenvironmental changes co-occur with mosaic somatic clonal expansions in normal skin and esophagus tissues
Authors: Munugula C. , Hu J. , Christodoulou E. , Yellapantula V.
Published: December 2022

The presence of somatic mutations, previously identified in cancers, are being increasingly recognized in normal tissues. While the role of microenvironment (ME) in tumor progression is well understood, the changes that occur in the microenvironment of normal tissues that harbor somatic mutations has not been systematically studied. Here, using normal RNA-Seq data accrued from 6544 samples across 27 tissue types from Genotype-Tissue Expression (GTEx) project, we studied the association of microenvironmental changes in the presence of somatic clonal expansions of previously implicated cancer genes. We focused our analysis on skin and esophagus since they have the highest number of samples and mutation burden together. We observed changes in microenvironmental cell-types previously implicated in tumor progression including endothelial cells, epithelial cells, pericytes, fibroblasts, chondrocytes, among others. The Epithelial-Mesenchymal-Transition (EMT) pathway is dysregulated in both skin and esophagus, along with increased hypoxia scores in samples with clonal expansions. These results suggest that microenvironmental changes play an important role in clonal expansions and potentially the initiating stages of cancer progression. Studying these changes may provide new avenues for early intervention of cancer, for targeted therapies, or enhance activities of conventional therapies.
En bloc resection of huge primary tumors with epidural involvement in the mobile spine using the “rotation–reversion” technique: Feasibility, safety, and clinical outcome of 11 cases
Authors: Lu Ming , Zhou Zhongxin , Chen Wei , Lei Zixiong , Dai Shuangwu , Hou Changhe , Du Shaohua , Jin Qinglin , Jin Dadi , Boriani Stefano , Li Haomiao
Published: December 2022

Background

En bloc resection of spinal tumors provides better local control and survival outcomes than intralesional resection. Safe margins during en bloc resection of primary spinal tumors with epidural involvement are required for improved outcomes. The present study describes a “rotation–reversion” technique that has been used for en bloc resection of huge primary tumors in the mobile spine with epidural involvement and reported the clinical outcomes in these patients.

Methods

All patients with primary spinal tumors who were treated with the rotation–reversion technique at our institution between 2015 and 2021 were evaluated retrospectively. Of the patients identified, those with both huge extraosseous soft-tissue masses and epidural involvement were selected for a case review. Clinical and radiological characteristics, pathologic findings, operative procedures, complications, and oncological and functional outcomes of these patients were reviewed.

Results

Of the 86 patients identified with primary spinal tumors who underwent en bloc resection using the rotation–reversion technique between 2015 and 2021, 11 had huge extraosseous soft-tissue masses with epidural involvement in the mobile spine. The average maximum size of these 11 tumors was 8.1 × 7.5 × 9.7 cm. Median follow-up time was 28.1 months, mean operation time was 849.1 min (range 465–1,340 min), and mean blood loss was 6,972.7 ml (range 2,500–17,700 ml), with 10 (91%) of the 11 patients experiencing perioperative complications. The negative margin rate was 91%, with only one patient (9%) experiencing local recurrence. Ten patients were able to walk normally or with a crutch at the last follow-up, whereas one was completely paralyzed preoperatively.

Conclusion

The rotation–reversion technique is an effective procedure for the en bloc resection of huge primary spinal tumors, with the extension of invasion in selected patients including not only the vertebral body but also the pedicle and part of the posterior arch.
Glutathione levels are associated with methotrexate resistance in acute lymphoblastic leukemia cell lines
Authors: Canevarolo Rafael Renatino , Melo Carolina Pereira de Souza , Cury Nathalia Moreno , Artico Leonardo Luiz , Corrêa Juliana Ronchi , Lau Yanca Tonhasca , Mariano Samara Sousa , Sudalagunta Praneeth Reddy , Brandalise Silvia Regina , Zeri Ana Carolina de Mattos , Yunes José Andrés
Published: December 2022

Introduction

Methotrexate (MTX), a folic acid antagonist and nucleotide synthesis inhibitor, is a cornerstone drug used against acute lymphoblastic leukemia (ALL), but its mechanism of action and resistance continues to be unraveled even after decades of clinical use.

Methods

To better understand the mechanisms of this drug, we accessed the intracellular metabolic content of 13 ALL cell lines treated with MTX by 1H-NMR, and correlated metabolome data with cell proliferation and gene expression. Further, we validated these findings by inhibiting the cellular antioxidant system of the cells in vitro and in vivo in the presence of MTX.

Results

MTX altered the concentration of 31 out of 70 metabolites analyzed, suggesting inhibition of the glycine cleavage system, the pentose phosphate pathway, purine and pyrimidine synthesis, phospholipid metabolism, and bile acid uptake. We found that glutathione (GSH) levels were associated with MTX resistance in both treated and untreated cells, suggesting a new constitutive metabolic-based mechanism of resistance to the drug. Gene expression analyses showed that eight genes involved in GSH metabolism were correlated to GSH concentrations, 2 of which (gamma-glutamyltransferase 1 [GGT1] and thioredoxin reductase 3 [TXNRD3]) were also correlated to MTX resistance. Gene set enrichment analysis (GSEA) confirmed the association between GSH metabolism and MTX resistance. Pharmacological inhibition or stimulation of the main antioxidant systems of the cell, GSH and thioredoxin, confirmed their importance in MTX resistance. Arsenic trioxide (ATO), a thioredoxin inhibitor used against acute promyelocytic leukemia, potentiated MTX cytotoxicity in vitro in some of the ALL cell lines tested. Likewise, the ATO+MTX combination decreased tumor burden and extended the survival of NOD scid gamma (NSG) mice transplanted with patient-derived ALL xenograft, but only in one of four ALLs tested.

Conclusion

Altogether, our results show that the cellular antioxidant defense systems contribute to leukemia resistance to MTX, and targeting these pathways, especially the thioredoxin antioxidant system, may be a promising strategy for resensitizing ALL to MTX.
Prognostic biomarker MCP-4 triggers epithelial-mesenchymal transition via the p38 MAPK pathway in ovarian cancer
Authors: Li Siting , Hu Yuexin , Liu Ouxuan , Li Xiao , Lin Bei
Published: December 2022

Background

Monocyte chemoattractant protein-4 (MCP-4/CCL13) is a proinflammatory factor that is overexpressed in various malignant tumors and may play an important role in tumor progression and metastasis. However, its role and mechanism of action in ovarian cancer remains unknown.

Methods

Immunohistochemistry (IHC) was performed to detect the expression of MCP-4 in ovarian cancer tissues, and the effect of MCP-4 on patient survival and prognosis was analyzed. Overexpression and suppression of MCP-4 in ovarian cancer cell lines were then established, and their effects on cell invasion, migration, and apoptosis were studied. ES-2 cell lines were employed to establish a peritoneal dissemination model in nude mice. Western blotting was performed to detect the expression of epithelial mesenchymal transition (EMT) markers and the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway.

Results

MCP-4 was highly expressed in ovarian cancer tissues and its expression level was related to the prognosis of patients with ovarian cancer. MCP-4 overexpression promoted the migration and invasion of ovarian cancer cells but inhibited apoptosis. MCP-4 overexpression increased the expression of MMP-2, MMP-9, N-cadherin, vimentin and Bcl2/Bax and decreased the expression of E-cadherin. MCP-4 overexpression increased the phosphorylation of the p38 MAPK pathway. The inhibition of MCP-4 expression indicated an opposite trend. In vivo experiments have also confirmed that MCP-4 overexpression can promote metastasis of ovarian cancer.

Conclusion

MCP-4 promotes ovarian cancer progression through the p38 MAPK signaling pathway, and may be a potential biomarker and therapeutic target for ovarian cancer.
Inflammation-related citrullination of matrisome proteins in human cancer
Authors: Rappu Pekka , Suwal Ujjwal , Siljamäki Elina , Heino Jyrki
Published: December 2022

Introduction

Protein arginine deiminases (PADs) are intracellular enzymes that may, especially in pathological conditions, also citrullinate extracellular substrates, including matrisome proteins such as structural proteins in extracellular matrix (ECM). PADs are abundantly expressed in human cancer cells. Citrullination of matrisome proteins has been reported in colon cancer but the phenomenon has never been systematically studied.

Methods

To gain a broader view of citrullination of matrisome proteins in cancer, we analyzed cancer proteomics data sets in 3 public databases for citrullinated matrisome proteins. In addition, we used three-dimensional cell cocultures of fibroblasts and cancer cells and analyzed citrullination of ECM.

Results and discussion

Our new analysis indicate that citrullination of ECM occurs in human cancer, and there is a significant variation between tumors. Most frequently citrullinated proteins included fibrinogen and fibronectin, which are typically citrullinated in rheumatoid inflammation. We also detected correlation between immune cell marker proteins, matrix metalloproteinases and ECM citrullination, which suggests that in cancer, citrullination of matrisome proteins is predominantly an inflammation-related phenomenon. This was further supported by our analysis of three-dimensional spheroid co-cultures of nine human cancer cell lines and fibroblasts by mass spectrometry, which gave no evidence that cancer cells or fibroblasts could citrullinate matrisome proteins in tumor stroma. It also appears that in the spheroid cultures, matrisome proteins are protected from citrullination.
Targeting H3K27me3 demethylase to inhibit Shh signaling and cholesterol metabolism in medulloblastoma growth
Authors: Deng Hongshi , Guo Xueli , Feng Na , Luo Yi , Liu Bei , Liu Shuzhen , Wu Jiang I. , Shi Xuanming
Published: December 2022

Previously we uncovered the epigenetic regulation of medulloblastoma that low levels of H3K27me3 are required for Shh target gene expression and medulloblastoma growth. Since Jmjd3, an H3K27me3 demethylase, is responsible for maintaining low H3K27me3 at Shh target genes, targeting Jmjd3 could be an efficient way to inhibit Shh signaling and medulloblastoma growth. Here we show that the small molecule GSK-J4, an inhibitor of Jmjd3, significantly inhibited the expression of Shh target genes in Shh responsive cell models and primary cerebellar granule neuron precursors. GSK-J4 also significantly reduced the growth of primary Shh medulloblastoma cultures. Treating human medulloblastoma cell line DaoY by GSK-J4 led to cell cycle arrest at G0/G1 phase with decreased cells in S-phase. Tumor cell proliferation was significantly inhibited by GSK-J4 treatment. Gene expression analyses showed that GSK-J4 additionally constrained the expression of key genes in cholesterol biosynthesis. Our results highlight the possibility that targeting H3K27me3 demethylase Jmjd3 with GSK-J4 to inhibit Shh signaling and cholesterol metabolism is a potential application to treat Shh medulloblastoma.
Case Report: A case of radioactive iodine-refractory thyroid cancer accompanying cervical lymph node metastasis treated with US-guided RFA combined with 125I seed implantation
Authors: Zhai Yuanpeng , Shao Yu , Li Qian
Published: December 2022

Background

Local control of metastases is critical to improving the life quality of patients with radioactive iodine-refractory (RAIR) thyroid cancer accompanying regional lymph node metastasis.

Case report

The reported patient suffered from RAIR thyroid cancer accompanying poorly controlled cervical lymph node metastasis. The patient’s lesions were controlled through 125I seed implantation combined with ultrasound-guided radio-frequency ablation (US-guided RFA). Such a combination therapy has not been reported to date.

Conclusion

This study found US-guided RFA combined with 125I seed implantation to be safe and effective for the control of cervical local metastases in patients with RAIR thyroid cancer.
Integrated genomic analysis to identify druggable targets for pancreatic cancer
Authors: Mugiyanto Eko , Adikusuma Wirawan , Irham Lalu Muhammad , Huang Wan-Chen , Chang Wei-Chiao , Kuo Chun-Nan
Published: December 2022

According to the National Comprehensive Cancer Network and the American Society of Clinical Oncology, the standard treatment for pancreatic cancer (PC) is gemcitabine and fluorouracil. Other chemotherapeutic agents have been widely combined. However, drug resistance remains a huge challenge, leading to the ineffectiveness of cancer therapy. Therefore, we are trying to discover new treatments for PC by utilizing genomic information to identify PC-associated genes as well as drug target genes for drug repurposing. Genomic information from a public database, the cBio Cancer Genomics Portal, was employed to retrieve the somatic mutation genes of PC. Five functional annotations were applied to prioritize the PC risk genes: Kyoto Encyclopedia of Genes and Genomes; biological process; knockout mouse; Gene List Automatically Derived For You; and Gene Expression Omnibus Dataset. DrugBank database was utilized to extract PC drug targets. To narrow down the most promising drugs for PC, CMap Touchstone analysis was applied. Finally, ClinicalTrials.gov and a literature review were used to screen the potential drugs under clinical and preclinical investigation. Here, we extracted 895 PC-associated genes according to the cBioPortal database and prioritized them by using five functional annotations; 318 genes were assigned as biological PC risk genes. Further, 216 genes were druggable according to the DrugBank database. CMap Touchstone analysis indicated 13 candidate drugs for PC. Among those 13 drugs, 8 drugs are in the clinical trials, 2 drugs were supported by the preclinical studies, and 3 drugs are with no evidence status for PC. Importantly, we found that midostaurin (targeted PRKA) and fulvestrant (targeted ESR1) are promising candidate drugs for PC treatment based on the genomic-driven drug repurposing pipelines. In short, integrated analysis using a genomic information database demonstrated the viability for drug repurposing. We proposed two drugs (midostaurin and fulvestrant) as promising drugs for PC.
Case report: Dramatic response to alectinib in a lung adenosquamous carcinoma patient harbouring a novel CPE-ALK fusion
Authors: Qin Yanyan , Li Fei , Tan Yuan , Duan Qianqian , Zhang Qin
Published: December 2022

Lung Adenosquamous carcinoma (ASC) is a rare histological subtype of lung cancer accounting for 0.4%–4% of all lung cancers. ASC is generally considered to be an aggressive cancer with poor prognosis. There is no specific standard treatment for ASC, and current treatment of ASC is relied on the guideline for non-small cell lung cancer (NSCLC). To date, only sporadic canonical EML4-ALK fusions have been reported in ASC patients, and the efficiency of ALK-TKI is still unclear in non-canonical ALK fusion positive ASC patients. Here we describe the case of a stage IV ASC patient harboring a novel CPE-ALK fusion detected via 74 genes panel analysis. Interestingly, the TP53 was wild-type and no another somatic mutation was found within 74 genes. In addition, immunohistochemical staining (IHC) also supports an oncogenic role for the CPE-ALK fusion. Based on these findings, the patient received alectinib 600 mg twice daily. After 4 months on treatment the patients achieved a radiological partial response (PR) and his symptoms were significantly relieved. Imaging showed that lesions of the patient were reduced, and the clinical evaluation was partial response (PR). To the best of our knowledge, this is the first report of a dramatic tumor response to alectinib in a patient with ASC harboring a CPE-ALK fusion. In addition, targeted NGS analysis may improve detection of ALK fusion in routine practice.
Effects of dehydroabietic acid on nontarget lipidomics and proteomics of HepG2
Authors: Xiahou Zhikai , Han Jun
Published: December 2022

Objective: Studies of the effects of dehydroabietic acid on the multiomics of HepG2 hepatoma carcinoma cells are currently lacking. In this study, the molecular mechanism of the influence of dehydroabietic acid on HepG2 cells was disclosed by studying lipidomics and proteomics. Correlations among multiomics conjoint analysis results were verified.

Methods: First, proteomics analysis of HepG2 cells was carried out using dehydroabietic acid. Differentially expressed proteins were screened and analyzed. Pathway enrichment analyses of differential proteins were compared, and the molecular mechanism was disclosed. Second, lipidomics analysis of HepG2 cells was conducted using dehydroabietic acid. The influence of dehydroabietic acid on HepG2 cells was determined on the lipid molecular level. Finally, a conjoint analysis of data related to differentially expressed proteins of ferroptosis and differentially changing lipid molecules was implemented.

Results: A total of 260 upregulated and 961 downregulated proteins were screened in the proteomics analysis. The top five significantly enriched pathways included ferroptosis, oxidative phosphorylation, and protein processing in the endoplasmic reticulum. In the lipidomics analysis, 30 significantly differential metabolites with upregulated and downregulated expression were identified, and differentially expressed lipids were mainly related to the metabolism of glyceryl phosphatide. According to the comprehensive multiomics analysis results, real-time quantitative PCR and the enzyme-linked immunosorbent assay (ELISA), ACSL3 participated in cardiolipin metabolism.

Conclusion: Dehydroabietic acid influences HepG2 cells through the above biological pathways.
PKHB1 peptide induces antiviral effects through induction of immunogenic cell death in herpes simplex keratitis
Authors: He Yun , Wang Chenchen , Liang Qi , Guo Rongjie , Jiang Jiaxuan , Shen Wenhao , Hu Kai
Published: December 2022

Herpes simplex keratitis (HSK) is a severe, infectious corneal disease caused by herpes simplex virus type 1 (HSV-1) infection. The increasing prevalence of acyclovir resistance, the side effects of hormonal drugs, and the ease of recurrence after surgery have made it crucial to develop new methods of treating HSK. HSV-1 evades the host immune response through various mechanisms. Therefore, we explored the role of the immunogenic cell death inducer PKHB1 peptide in HSK. After subconjunctival injection of PKHB1 peptide, we observed the ocular surface lesions and survival of HSK mice and detected the virus levels in tear fluid, corneas, and trigeminal ganglions. We found that PKHB1 peptide reduced HSV-1 levels in the eye and alleviated the severity of HSK. Moreover, it increased the number of corneal infiltrating antigen-presenting cells (APCs), such as macrophages and dendritic cells, and CD8+ T cells in ocular draining lymph nodes. We further observed that PKHB1 peptide promoted the exposure of calreticulin, as well as the release of ATP and high-mobility group box 1 in HSV-1-infected cells in vitro. Our findings suggested that PKHB1 peptide promoted the recruitment and maturation of APCs by inducing the release of large amounts of damage-associated molecular patterns from infected cells. APCs then phagocytized antigenic materials and translocated to the lymph nodes, triggering a cytotoxic T lymphocyte-dependent immune response that ultimately alleviated HSK.
A novel biflavone from Reineckia carnea induces apoptosis of human renal cancer 786-O cells
Authors: Yang Jianqiong , Xiao Bang , Li Yamei , Liu Xiaoxuan , Zhang Minhong , Luo Yaoling , Wang Biao , Liu Hai
Published: December 2022

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system, which is highly invasive, metastatic, and insensitive to radiotherapy and chemotherapy. Chinese herbal medicine has always been an important source of anti-tumor drug development. Reineckia carnea Kunth is a traditional herb commonly used by the Miao nationality in southwest China. In this study, the extract of Reineckia carnea was isolated and purified by reverse phase preparative chromatography and other chromatographic techniques. According to the physicochemical properties and spectral data, the structure of the compound was identified, and a novel biflavone compound named Reineckia-biflavone A (RFA) was obtained. The result of antiproliferative activity showed that RFA had cytotoxicity on 786-O cells with an IC50 value of 19.34 μmol/L. The results of CCK-8 and hemolysis assays showed that RFA was not significantly cytotoxic to both red blood cells (RBC) and peripheral blood mononuclear cells (PBMC). By Hoechst 33258 apoptosis staining, typical apoptotic morphology was observed under fluorescence microscope. RFA could induce the apoptosis of 786-O cells with the increase of apoptosis rate. The cell cycle tests showed that the cell proportion was obviously arrested in the S phase. At the same time, RFA could decrease the mitochondrial membrane potential and increase the intracellular free Ca2+ concentration. Western blot showed that the expression levels of pro-apoptotic proteins (Bax, Caspase-3, Cleaved Caspase-3, and Cytochrome c) in cells rose, while the expression level of anti-apoptotic proteins (Bcl-2) declined significantly. In conclusion, this study suggests that the RFA is a new biflavone determined by SciFinder retrieval. The apoptosis may be triggered by RFA through the mitochondrial pathway, which is mediated by up-regulating the intracellular calcium ion, down-regulating the mitochondrial membrane potential, and changing the apoptosis-related proteins.
Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system
Authors: Jiang Tingting , Su Hui , Li Yanping , Wu Yuanlin , Ming Yue , Li Chen , Fu Ruoqiu , Feng Lu , Li Ziwei , Li Li , Ni Rui , Liu Yao
Published: December 2022

Objective: In recent years, the emergence of immunomodulatory drugs (IMiDs) has significantly improved clinical outcomes in patients with multiple myeloma (MM); however, serious adverse events (AEs) have hindered their safe clinical application. This study aimed to characterize the safety profiles and differences in IMiDs through a disproportionality analysis using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), a post-marketing surveillance database.

Methods: This study filtered reports of thalidomide, lenalidomide, and pomalidomide as primary suspect drugs in FAERS files from January 2013 to December 2021. AEs in the reports were retrieved according to the preferred terms (PTs) of the Medical Dictionary for Regulatory Activities. Furthermore, we detected safety signals using the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian belief propagation neural network (BCPNN). When all three algorithms showed an association between the target drug and the AE, a positive signal was generated.

Results: We extracted 9,968 thalidomide, 231,926 lenalidomide, and 55,066 pomalidomide AE reports. AEs were more common in male patients and in those >44 years old. Important safety signals were detected based on the system organ classes (SOC), including thalidomide (cardiac disorders: ROR, 2.87; PRR, 2.79; IC 1.22), lenalidomide (gastrointestinal disorders: ROR, 2.38; PRR, 2.27; IC 0.75), and pomalidomide (respiratory, thoracic, and mediastinal disorders: ROR, 2.14; PRR, 2.09; IC 0.85). Within the PT level, we identified novel risk signals: the thalidomide-induced second primary malignancy (SPM) signal was significant; lenalidomide reduced the success rate of hematopoietic stem cell collection; and three IMiDs may cause human chorionic gonadotropin increase, but this needs to be proven by clinical data. Pneumonia, sepsis, and renal failure are common risk factors for death due to IMiDs. Compared with thalidomide and lenalidomide, pomalidomide has a lower risk of venous thromboembolism (VTE) and is beneficial to patients with renal insufficiency.

Conclusion: Mining data from FAERS resulted in novel AE signals, including adenocarcinoma of colon, harvest failure of blood stem cells, and increased levels of human chorionic gonadotropin. Further investigation is required to verify the significance of these signals. Moreover, IMiDs showed differences in safety reports, which should be emphasized by clinicians.
Study on external cavity diode laser with a wide mode-hopping free tuning range
Authors: Zhang Aiguo , Qiao Shan , Sheng Liwen , Huang Lin , Liu Zhiming , Ju Junwei , Zhang Zhihui , Yin Bingqi , Li Peng , Liu Jiaqing , Wei Yu
Published: December 2022

A wide mode-hopping free and narrow linewidth tunable laser diode source with a Littman-Metcalf arrangement based on a diffraction grating is presented. Several experiments are carried out to demonstrate the tuning characteristics and spectral linewidth of the proposed external-cavity diode laser source. A wide no mode-hopping continuous wavelength tuning range about 59.13 nm in ultra-C-band with a narrow spectral linewidth of less than 100 kHz is obtained. An optical signal to noise ratio of more than 65 dB and an output power more than 14.8 dBm over the whole tuning range can also be realized in a long-term free running condition. The proposed tunable laser allows simultaneously mode-hopping free and narrow linewidth tunable radiation, thus opening a door for practical application such as coherent detection.
Modeling ameloblast-matrix interactions using 3D cell culture
Authors: Visakan Gayathri , Bapat Rucha Arun , Su Jingtan , Moradian-Oldak Janet
Published: December 2022

The distinct morphology adopted by ameloblasts during amelogenesis is highly stage specific and involved intimately with the development of a hierarchical enamel microstructure. The molecular mechanisms that govern the development of an elongated and polarized secretory ameloblast morphology and the potential roles played by the enamel matrix proteins in this process are not fully understood. Thus far, the in vitro models that have been developed to mimic these early cell-matrix interactions have either been unable to demonstrate direct morphological change or have failed to adapt across ameloblast cell lines. Here, we use a recently established 3D cell culture model to examine the interactions between HAT-7 cells and the major enamel matrix proteins, amelogenin and ameloblastin. We demonstrate that HAT-7 cells selectively respond to functional EMPs in culture by forming clusters of tall cells. Aspect ratio measurements from three-dimensional reconstructions reveal that cell elongation is 5-times greater in the presence of EMPs when compared with controls. Using confocal laser scanning microscopy, we observe that these clusters are polarized with asymmetrical distributions of Par-3 and claudin-1 proteins. The behavior of HAT-7 cells in 3D culture with EMPs is comparable with that of ALC and LS-8 cells. The fact that the 3D model presented here is tunable with respect to gel substrate composition and ameloblast cell type highlights the overall usefulness of this model in studying ameloblast cell morphology in vitro.
Cerebral multimodality monitoring in adult neurocritical care patients with acute brain injury: A narrative review
Authors: Tas Jeanette , Czosnyka Marek , van der Horst Iwan C. C. , Park Soojin , van Heugten Caroline , Sekhon Mypinder , Robba Chiara , Menon David K. , Zeiler Frederick A. , Aries Marcel J. H.
Published: December 2022

Cerebral multimodality monitoring (MMM) is, even with a general lack of Class I evidence, increasingly recognized as a tool to support clinical decision-making in the neuroscience intensive care unit (NICU). However, literature and guidelines have focused on unimodal signals in a specific form of acute brain injury. Integrating unimodal signals in multiple signal monitoring is the next step for clinical studies and patient care. As such, we aimed to investigate the recent application of MMM in studies of adult patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), acute ischemic stroke (AIS), and hypoxic ischemic brain injury following cardiac arrest (HIBI). We identified continuous or daily updated monitoring modalities and summarized the monitoring setting, study setting, and clinical characteristics. In addition, we discussed clinical outcome in intervention studies. We identified 112 MMM studies, including 11 modalities, over the last 7 years (2015–2022). Fifty-eight studies (52%) applied only two modalities. Most frequently combined were ICP monitoring (92 studies (82%)) together with PbtO2 (63 studies (56%). Most studies included patients with TBI (59 studies) or SAH (53 studies). The enrollment period of 34 studies (30%) took more than 5 years, whereas the median sample size was only 36 patients (q1- q3, 20–74). We classified studies as either observational (68 studies) or interventional (44 studies). The interventions were subclassified as systemic (24 studies), cerebral (10 studies), and interventions guided by MMM (11 studies). We identified 20 different systemic or cerebral interventions. Nine (9/11, 82%) of the MMM-guided studies included clinical outcome as an endpoint. In 78% (7/9) of these MMM-guided intervention studies, a significant improvement in outcome was demonstrated in favor of interventions guided by MMM. Clinical outcome may be improved with interventions guided by MMM. This strengthens the belief in this application, but further interdisciplinary collaborations are needed to overcome the heterogeneity, as illustrated in the present review. Future research should focus on increasing sample sizes, improved data collection, refining definitions of secondary injuries, and standardized interventions. Only then can we proceed with complex outcome studies with MMM-guided treatment.
Effects of selenium solution on the crystalline structure, pasting and rheological properties of common buckwheat starch
Authors: Wang Jiale , Leng Jiajun , Gao Licheng , Han Mengru , Wu Yixin , Lei Xinhui , Gao Jinfeng
Published: December 2022

Selenium is an important element that affects human growth and development, and also affects the yield and quality of common buckwheat. In our study, two common buckwheat varieties were sprayed with different concentrations (0 g/hm2, 5 g/hm2, 20 g/hm2) of sodium selenite solution at the initial flowering period and the full flowering period, respectively, to determine the effects of selenium solution on the physicochemical properties of common buckwheat starch. With increasing selenium levels, the amylose content, peak viscosity, breakdown, relative crystallinity, pasting temperature and gelatinization enthalpy first decreased and then increased, while the transparency showed a trend of increasing and then decreasing. All samples exhibited a typical A-type pattern, while at high selenium level, the degree of short-range order of common buckwheat starches changed. From the rheological properties, it can be seen that the starch paste is dominated by elastic properties, while the low selenium treatment decreases the viscosity of the starch paste. These results showed that spraying different concentrations of selenium solutions at different periods significantly affected the physicochemical properties of common buckwheat starch.
Mechanosensing, from forces to structures
Authors: Zhao Feng , Long Yuchen
Published: December 2022

Sessile plants evolve diverse structures in response to complex environmental cues. These factors, in essence, involve mechanical stimuli, which must be sensed and coordinated properly by the plants to ensure effective growth and development. While we have accumulated substantial knowledge on plant mechanobiology, how plants translate mechanical information into three-dimensional structures is still an open question. In this review, we summarize our current understanding of plant mechanosensing at different levels, particularly using Arabidopsis as a model plant system. We also attempt to abstract the mechanosensing process and link the gaps from mechanical cues to the generation of complex plant structures. Here we review the recent advancements on mechanical response and transduction in plant morphogenesis, and we also raise several questions that interest us in different sections.
Characterization and genetic dissection of maize ear leaf midrib acquired by 3D digital technology
Authors: Wu Sheng , Wang Jinglu , Zhao Yanxin , Wen Weiliang , Zhang Ying , Lu Xianju , Wang Chuanyu , Liu Kai , Chen Bo , Guo Xinyu , Zhao Chunjiang
Published: December 2022

The spatial morphological structure of plant leaves is an important index to evaluate crop ideotype. In this study, we characterized the three-dimensional (3D) data of the ear leaf midrib of maize at the grain-filling stage using the 3D digitization technology and obtained the phenotypic values of 15 traits covering four different dimensions of the ear leaf midrib, of which 13 phenotypic traits were firstly proposed for featuring plant leaf spatial structure. Cluster analysis results showed that the 13 traits could be divided into four groups, Group I, -II, -III and -IV. Group I contains HorizontalLength, OutwardGrowthMeasure, LeafAngle and DeviationTip; Group II contains DeviationAngle, MaxCurvature and CurvaturePos; Group III contains LeafLength and ProjectionArea; Group IV contains TipTop, VerticalHeight, UpwardGrowthMeasure, and CurvatureRatio. To investigate the genetic basis of the ear leaf midrib curve, 13 traits with high repeatability were subjected to genome-wide association study (GWAS) analysis. A total of 828 significantly related SNPs were identified and 1365 candidate genes were annotated. Among these, 29 candidate genes with the highest significant and multi-method validation were regarded as the key findings. In addition, pathway enrichment analysis was performed on the candidate genes of traits to explore the potential genetic mechanism of leaf midrib curve phenotype formation. These results not only contribute to further understanding of maize leaf spatial structure traits but also provide new genetic loci for maize leaf spatial structure to improve the plant type of maize varieties.
Clonal integration benefits an invader in heterogeneous environments with reciprocal patchiness of resources, but not its native congener
Authors: Zhang Xiao-Mei , He Lin-Xuan , Xiao Xiao , Lei Jing-Pin , Tang Min , Lei Ning-Fei , Yu Fei-Hai , Chen Jin-Song
Published: December 2022

Many of the world’s most invasive plants are clonal, and clonal functional traits are suggested to contribute to their invasiveness. Clonal integration is one of the most important clonal functional traits, but it is still unclear whether clonal integration can benefit invasive alien clonal plants more than native ones in heterogeneous environments with reciprocal patchiness of resources and whether invasive plants show a higher capacity of division of labor than native ones in such environments. We grew connected (allowing clonal integration) and disconnected (preventing clonal integration) ramet pairs of an invasive plant Wedelia trilobata and its occurring native congener W. chinensis in the environment consisting of reciprocal patches of light and soil nutrients (i.e., a high-light but low-nutrient patch and a low-light but high-nutrient patch). Clonal integration greatly promoted the growth of the invasive species, but had no significant effect on the native one. Both invasive and native species showed division of labor in terms of morphology, biomass allocation, and/or photosynthetic physiology, but the capacity of labor division did not differ between the invasive and the native species. We conclude that in heterogeneous environments consisting of reciprocal patches of resources, which are common in nature, clonal integration can confer invasive plants a competitive advantage over natives, but this difference is not related to their capacity of labor division. This study highlights the importance of clonal integration for plants in heterogeneous environments and suggests that clonal integration can contribute to the invasion success of alien clonal plants.
A review of strategies used to identify transposition events in plant genomes
Authors: Bajus Marko , Macko-Podgórni Alicja , Grzebelus Dariusz , Baránek Miroslav
Published: December 2022

Transposable elements (TEs) were initially considered redundant and dubbed ‘junk DNA’. However, more recently they were recognized as an essential element of genome plasticity. In nature, they frequently become active upon exposition of the host to stress conditions. Even though most transposition events are neutral or even deleterious, occasionally they may happen to be beneficial, resulting in genetic novelty providing better fitness to the host. Hence, TE mobilization may promote adaptability and, in the long run, act as a significant evolutionary force. There are many examples of TE insertions resulting in increased tolerance to stresses or in novel features of crops which are appealing to the consumer. Possibly, TE-driven de novo variability could be utilized for crop improvement. However, in order to systematically study the mechanisms of TE/host interactions, it is necessary to have suitable tools to globally monitor any ongoing TE mobilization. With the development of novel potent technologies, new high-throughput strategies for studying TE dynamics are emerging. Here, we present currently available methods applied to monitor the activity of TEs in plants. We divide them on the basis of their operational principles, the position of target molecules in the process of transposition and their ability to capture real cases of actively transposing elements. Their possible theoretical and practical drawbacks are also discussed. Finally, conceivable strategies and combinations of methods resulting in an improved performance are proposed.
SEP-like genes of Gossypium hirsutum promote flowering via targeting different loci in a concentration-dependent manner
Authors: Chen Liting , Yan Yuanyuan , Ke Huifeng , Zhang Zihao , Meng Chengsheng , Ma Limei , Sun Zhengwen , Chen Bin , Liu Zhengwen , Wang Guoning , Yang Jun , Wu Jinhua , Li Zhikun , Wu Liqiang , Zhang Guiyin , Zhang Yan , Wang Xingfen , Ma Zhiying
Published: December 2022

SEPgenes are famous for their function in the morphological novelty of bisexual flowers. Although the diverse functions ofSEPgenes were reported, only the regulatory mechanisms underlying floral organ development have been addressed. In this study, we identifiedSEP-like genes inGossypiumand found thatSEP3genes were duplicated in diploid cotton varieties.GhSEP4.1andGhSEP4.2were abundantly transcribed in the shoot apical meristem (SAM), but onlyGhSEP4.2was expressed in the leaf vasculature. The expression pattern ofGhSEPs in floral organs was conserved with that of homologs inArabidopsis, except forGhSEP2that was preponderantly expressed in ovules and fibers. The overexpression and silencing of each singleGhSEPgene suggested their distinct role in promoting floweringviadirect binding toGhAP1andGhLFYgenomic regions. The curly leaf and floral defects in overexpression lines with a higher expression ofGhSEPgenes revealed the concentration-dependent target gene regulation of GhSEP proteins. Moreover, GhSEP proteins were able to dimerize and interact with flowering time regulators. Together, our results suggest the dominant role ofGhSEP4.2in leaves to promote floweringvia GhAP1-A04, and differently accumulated GhSEP proteins in the SAM alternately participate in forming the dynamic tetramer complexes to target at the different loci ofGhAP1andGhLFYto maintain reproductive growth. The regulatory roles of cottonSEPgenes reveal their conserved and diversified functions.
PE-Iv (Panorama Education-Italian version): the adaptation/validation of 5 scales, a step towards a SEL approach in Italian schools
Authors: Lattke Lynda S. , De Lorenzo Aurelia , Settanni Michele , Rabaglietti Emanuela
Published: December 2022

Implementing a Social and Emotional Learning (SEL) approach in school requires monitoring certain skills. As awareness of SEL increases in Italy, it is necessary to provide instruments to monitor these skills within a systemic approach. This study presents the cultural adaptation/validation of 5 scales from Panorama Education, which are widely used in school districts in the United States, to the Italian middle/high school context: Grit, Sense of Belonging, Self-Management, Social Awareness, and Self-Efficacy. After cultural adaptation, 709 middle/high school students answered an online questionnaire (2021). Psychometric properties showed good internal consistency and confirmatory factor analysis showed a good fit index. The differences in gender and grade level support the validity of the instrument.
The influence of androgynous streamers on consumers’ product preferences
Authors: Wenting Feng , Shuyun Xue , Ying Yang , Hai Huang
Published: December 2022

Since the rapid development of network technology, the rise of live-streaming shopping platforms has followed. Some streamers influence consumers’ preferences for products through their gender role attributes, thus generating great commercial value. Based on attachment theory and using an experimental approach, this study explored the impact of streamers’ gender roles (single gender/androgyny) on consumers’ preferences through 2 studies. Study 1 shows the androgynous streamer elicits a higher product preference than the single-gender (masculine and feminine) streamer. Study 2 demonstrates the moderating effect of gender stereotypes through 2 experiments to construct clear boundary conditions for the main effect and the results show that regardless of whether the streamer is male or female when individuals have a high gender stereotype, the single-gender streamer leads to a higher product preference than the androgynous streamer. When individuals have a low gender stereotype, the androgynous streamer promotes a higher product preference than the single-gender streamer.
Childhood emotional abuse and cyberbullying perpetration among Chinese university students: The chain mediating effects of self-esteem and problematic social media use
Authors: Xu Wei , Zheng Shujie
Published: December 2022

Childhood abuse has been shown to have a range of adverse physical and psychological consequences, including aggression and bullying. While researchers have explored the relationship between childhood abuse and cyberbullying, little is known about the impact of emotional abuse on cyberbullying. This study examined the link between childhood emotional abuse (CEA) and cyberbullying perpetration among university students in the Chinese cultural context, as well as the chain mediating effect of self-esteem and Problematic Social Media Use (PSMU). A total of 835 university students (18–25 years old; 293 males, 542 females; Mage = 19.44 years, SD = 1.28) completed the Childhood Trauma Questionnaire Short-Form (CTQ-SF), Rosenberg Self-Esteem Scale (RSES), the Social Media Use Questionnaire (SMUQ), and Cyberbullying Inventory (CBI). The results showed that CEA and PSMU were positively correlated with cyberbullying; self-esteem was negatively correlated with cyberbullying. Besides, self-esteem and PSMU sequentially mediated the relationship between CEA and cyberbullying perpetration. The findings indicate that childhood emotional abuse may lower self-esteem and cause problematic social media use, which increases cyberbullying perpetration.
College students’ learning perceptions and outcomes in different classroom environments: A community of inquiry perspective
Authors: Hu Yan , Huang Jinyan , Kong Fanzhe
Published: December 2022

Introduction

This study examined the significant differences in Chinese college students’ learning perceptions and outcomes between the “quasi smart” and smart classrooms under the perspective of the community of inquiry (CoI) framework.

Methods

The participants were 275 freshmen students who took the “college physics” hybrid course in the spring of 2022 at a four-year university in central China. Data were collected from the CoI survey, a follow-up focus group interview with ten randomly selected student participants, and a semi-structured interview with the instructor.

Results and discussion

The results indicated that the students’ perceptions of the teaching, social, and cognitive presences were significantly higher in the smart classroom than in the “quasi smart” classroom; further, students in the smart classroom achieved significantly higher course marks than those in the “quasi smart” classroom. The pros and cons of these two different classroom environments were identified by the participating students and their course instructor.