An acridone based fluorescent dye for lipid droplet tracking and cancer diagnosis.

Lipid droplets (LDs) are spherical organelles that localize in the cytosol of eukaryotic cells. Different proteins are embedded on the surface of LDs, so LDs play a vital role in the physiological activities of cells. The dysregulation of LDs is associated with various human diseases, such as diabetes and obesity. Therefore, it is essential to develop a fluorescent dye that labels LDs to detect and monitor illnesses. In this study, we developed the compound BDAA12C for staining LDs in cells. BDAA12C exhibits excellent LD specificity and low toxicity, enabling us to successfully stain and observe the fusion of LDs in A549 cancer cells. Furthermore, we also successfully distinguished A549 cancer cells and MRC-5 normal cells in a co-culture experiment and in normal and tumour tissues. Interestingly, we found different localizations of BDAA12C in well-fed and starved A549 cancer cells and consequently illustrated the transfer of fatty acids (FAs) from LDs to mitochondria to supply energy for ß-oxidation upon starvation. Therefore, BDAA12C is a promising LD-targeted probe for cancer diagnosis and tracking lipid trafficking within cells.

Ligand effect of cyclometallated iridium(iii) complexes on N-alkylation of amines in hydrogen borrowing reactions.

Dinuclear iridium complexes with the general formula (C^N)2Ir(µ-Cl)2Ir(C^N)2 (C^N = bidentate ligand with carbon and nitrogen donor atoms) were prepared and used in catalytic systems for N-alkylation of amines through the hydrogen borrowing pathway. Triphenylphosphine derivatives were used as auxiliary in catalytic systems to provide excellent conversion of amines to N-alkylation products in yields ranging from 57% to 100%. The catalytic ability of the catalyst depends on the structure of its coordination ligands, including bidentate ligands (C^N) and triphenylphosphine derivatives. These catalytic systems adopt an environmentally friendly and sustainable reaction process through a hydrogen self-transfer strategy, using readily available alcohols as alkylating agents without the need for bases, solvents, and other additives, showing potential in the synthetic and pharmaceutical industries.

Diploid and tetraploid genomes of Acorus and the evolution of monocots.

Monocots are a major taxon within flowering plants, have unique morphological traits, and show an extraordinary diversity in lifestyle. To improve our understanding of monocot origin and evolution, we generate chromosome-level reference genomes of the diploid Acorus gramineus and the tetraploid Ac. calamus, the only two accepted species from the family Acoraceae, which form a sister lineage to all other monocots. Comparing the genomes of Ac. gramineus and Ac. calamus, we suggest that Ac. gramineus is not a potential diploid progenitor of Ac. calamus, and Ac. calamus is an allotetraploid with two subgenomes A, and B, presenting asymmetric evolution and B subgenome dominance. Both the diploid genome of Ac. gramineus and the subgenomes A and B of Ac. calamus show clear evidence of whole-genome duplication (WGD), but Acoraceae does not seem to share an older WGD that is shared by most other monocots. We reconstruct an ancestral monocot karyotype and gene toolkit, and discuss scenarios that explain the complex history of the Acorus genome. Our analyses show that the ancestors of monocots exhibit mosaic genomic features, likely important for that appeared in early monocot evolution, providing fundamental insights into the origin, evolution, and diversification of monocots.

Go Green, Go Social: Exploring the Antecedents of Pro-Environmental Behaviors in Social Networking Sites beyond Norm Activation Theory.

The paucity of environmental resources and the threatening warning of global climate change have led to increasing research on environmental issues [e.g., pro-environmental behaviors (PEBs)]. Although norm activation theory (NAT) is a well-recognized theory for approaching PEBs, existing works appear insufficient to explain PEB in the context of social networking sites (SNSs) without taking contextual, emotional, and social factors into account. Grounded in the egocentric tactician model (ETM), NAT, along with the notions of guilt and social stressors, this study integrates a new ETM path, a supplemented emotional path, alongside the conventional NAT path to achieve a more complete picture of what are crucial determinants of PEBs in the context of SNSs. Social stressors positively moderate the emotional path. Data collected from 897 Facebook users confirm all of our proposed hypotheses. Results indicate that beyond the traditional NAT path, the new ETM path and the emotional path add values to illustrate PEBs on SNSs, and new constructs of self-influence on SNSs (SIS) and guilt remarkably drive PEBs alongside personal norms. Implications for theory and practice are discussed, and guidelines for future research are identified.

Gu Sui Bu (Drynaria fortunei J. Sm.) antagonizes glucocorticoid-induced mineralization reduction in zebrafish larvae by modulating the activity of osteoblasts and osteoclasts.

ETHNOPHARMACOLOGICAL RELEVANCE: Gu Sui Bu (GSB), the dried rhizome of Drynaria fortunei J. Sm., is widely used in traditional Chinese medicine for treating fractures and osteoporosis. Although glucocorticoids are widely prescribed in modern medicine, the efficacy of GSB in treating glucocorticoid-induced osteoporosis (GIOP) remains unclear. AIM OF THE STUDY: GIOP is one of the most prevalent forms of osteoporosis and increases the risk of fracture, which can cause severe complications in elderly people. Safe, efficacious, and cost-effective treatment options for GIOP are thus warranted. The present study investigated the efficacy and mechanism of GSB for treating GIOP. MATERIALS AND METHODS: We established an efficient and robust in vivo GIOP model by optimizing zebrafish larvae rearing conditions and the dose and duration of dexamethasone treatment. Bone calcification was evaluated through calcein staining. To quantify the degree of vertebral mineralization in the larvae, we developed a scoring system based on the rate of vertebral calcification; this system reduced quantification errors among individual zebrafish caused by inconsistencies in staining or imaging parameters. Quantitative real-time polymerase chain reaction was used to access the expression levels of genes essential to the differentiation and function of bone cells. High-performance liquid chromatography was employed to identify naringin in the GSB extract. RESULTS: GSB significantly reversed the dexamethasone-induced calcification delay in zebrafish larvae. GSB enhanced osteoblast activity by increasing the expression of collagen I, osteopontin, and osteonectin and repressed bone resorption by decreasing the expression of matrix metalloproteinases (mmps), including mmp9 and mmp13a. We also identified naringin as one of the constituents of GSB responsible for the herbal extract's anti-GIOP activity. CONCLUSIONS: Using the in vivo zebrafish GIOP model that we established, the efficacy of traditional Chinese medicines in treating GIOP could be systematically investigated. GSB has an osteogenic effect and may thus be an efficacious and cost-effective treatment option for GIOP. Notably, bone resorption activity was found to be retained after GSB treatment, which would be beneficial for maintaining normal bone remodeling.

Genomes of leafy and leafless Platanthera orchids illuminate the evolution of mycoheterotrophy.

To improve our understanding of the origin and evolution of mycoheterotrophic plants, we here present the chromosome-scale genome assemblies of two sibling orchid species: partially mycoheterotrophic Platanthera zijinensis and holomycoheterotrophic Platanthera guangdongensis. Comparative analysis shows that mycoheterotrophy is associated with increased substitution rates and gene loss, and the deletion of most photoreceptor genes and auxin transporter genes might be linked to the unique phenotypes of fully mycoheterotrophic orchids. Conversely, trehalase genes that catalyse the conversion of trehalose into glucose have expanded in most sequenced orchids, in line with the fact that the germination of orchid non-endosperm seeds needs carbohydrates from fungi during the protocorm stage. We further show that the mature plant of P. guangdongensis, different from photosynthetic orchids, keeps expressing trehalase genes to hijack trehalose from fungi. Therefore, we propose that mycoheterotrophy in mature orchids is a continuation of the protocorm stage by sustaining the expression of trehalase genes. Our results shed light on the molecular mechanism underlying initial, partial and full mycoheterotrophy.

Improved Fixation Stability of a Dedicated Rib Fixation System in Flail Chest: A Retrospective Study.

Background and Objectives: Flail chest typically results from major trauma to the thoracic cage and is accompanied by multiple rib fractures. It has been well documented that surgical fixation of rib fractures can decrease both morbidity and mortality rates. This study aimed to evaluate the effectiveness of a dedicated APS Rib Fixation System, which features a pre-contoured design based on anatomical rib data of the Asian population. Materials and Methods: We reviewed 43 consecutive patients, who underwent surgical stabilization for flail chest with the traditional Mini bone plate (n = 20), APS plate (n = 13), or Mini + APS (n = 10). Demographic and injury variables were documented. We used X-ray radiography to determine plate fractures and screw dislocations after surgical fixation. Results: No statistical differences were noted in the demographic or injury variables. APS plates demonstrated fewer cases of plate fractures and screw dislocations than Mini plates (OR = 0.091, p = 0.008). Conclusions: The pre-contoured design of the APS plate demonstrated a superior rib implant failure rate as compared to the traditional Mini bone plate. Our study indicates that the APS plate may serve as an effective surgical tool for the treatment of flail chest.

A Novel Role of Arrhythmia-Related Gene KCNQ1 Revealed by Multi-Omic Analysis: Theragnostic Value and Potential Mechanisms in Lung Adenocarcinoma.

The early diagnosis, prognostic prediction, and personalized therapy of lung adenocarcinoma (LUAD) remains a challenging issue. KCNQ1 (potassium voltage-gated channel subfamily Q Member 1) is implicated in long QT syndrome (LQTS) and cardiac arrhythmia, while its significance in LUAD remains unclear. In this study, we aimed to explore the significance of KCNQ1 in terms of clinical value, tumor immunity, underlying mechanisms, and a precision medicine approach by means of multi-omics analysis. The association of KCNQ1 with LUAD was first explored. Both altered variants and high expression of KCNQ1 in a TCGA-LUAD cohort indicated a favorable outcome. KCNQ1 levels had a negative correlation with tumor proliferation index Ki67 levels. siRNA-knockdown of KCNQ1 promoted the migration ability of lung cancer cells. KCNQ1 levels were decreased in LUAD tissue compared to normal tissue. A receiver operating characteristic (ROC) curve indicated good diagnostic efficiency of KCNQ1. High KCNQ1 is associated with an immunoactive profile of immune infiltration and immunomodulators and is involved in the inhibition of the cell cycle and DNA replication. Lapatinib was identified as a potent drug for LUAD in the context of low KCNQ1. This study unveiled the significance of KCNQ1 in diagnosis and prognosis and provided a corresponding precision medicine strategy for LUAD.

Surgical stabilization of the ipsilateral scapula and rib fractures using the mirror Judet approach: a preliminary result.

BACKGROUND: We report our preliminary results using a single approach, the mirror Judet approach, for patients with both ipsilateral scapula and multiple rib fractures. METHODS: Five consecutive patients [median age: 56 years (range: 44 ~ 60)] with ipsilateral scapula and multiple rib fractures that met the surgical indications were retrospectively reviewed. A single approach, the mirror Judet approach, was used for surgical stabilization of the scapula and targeted rib fractures. Thoracoscopic surgery was performed first for management of associated lung lesions and marking the targeted rib. All patients received the same rehabilitation protocol and a minimum 12-month follow-up. RESULTS: All surgically-fixed fractures eventually united without malunion. No complaints of intercostal neuralgia, infection, or other complications were seen. The mean range of motion in the injured shoulder returned to at least 90% of the contralateral side range. The mean Disabilities of the Arm, Shoulder, and Hand score at the 12th month was 2.0 (range: 0-7). All patients were able to return to their previous work. CONCLUSION: The mirror Judet approach allows for the surgical stabilization of the ipsilateral scapula and multiple rib fractures using the same approach and provides acceptable functional outcomes in well-selected patients. LEVEL OF EVIDENCE: Level IV.

R2R3-MYB genes coordinate conical cell development and cuticular wax biosynthesis in Phalaenopsis aphrodite.

Petals of the monocot Phalaenopsis aphrodite (Orchidaceae) possess conical epidermal cells on their adaxial surfaces, and a large amount of cuticular wax is deposited on them to serve as a primary barrier against biotic and abiotic stresses. It has been widely reported that subgroup 9A members of the R2R3-MYB gene family, MIXTA and MIXTA-like in eudicots, act to regulate the differentiation of conical epidermal cells. However, the molecular pathways underlying conical epidermal cell development and cuticular wax biosynthesis in monocot petals remain unclear. Here, we characterized two subgroup 9A R2R3-MYB genes, PaMYB9A1 and PaMYB9A2 (PaMYB9A1/2), from P. aphrodite through the transient overexpression of their coding sequences and corresponding chimeric repressors in developing petals. We showed that PaMYB9A1/2 function to coordinate conical epidermal cell development and cuticular wax biosynthesis. In addition, we identified putative targets of PaMYB9A1/2 through comparative transcriptome analyses, revealing that PaMYB9A1/2 acts to regulate the expression of cell wall-associated and wax biosynthetic genes. Furthermore, a chemical composition analysis of cuticular wax showed that even-chain n-alkanes and odd-chain primary alcohols are the main chemical constituents of cuticular wax deposited on petals, which is inconsistent with the well-known biosynthetic pathways of cuticular wax, implying a distinct biosynthetic pathway occurring in P. aphrodite flowers. These results reveal that the function of subgroup 9A R2R3-MYB family genes in regulating the differentiation of epidermal cells is largely conserved in monocots and dicots. Furthermore, both PaMYB9A1/2 have evolved additional functions controlling the biosynthesis of cuticular wax.

Multi-Omics Reveal the Immunological Role and the Theragnostic Value of miR-216a/GDF15 Axis in Human Colon Adenocarcinoma.

Colon adenocarcinoma (COAD) is the most common type of gastrointestinal cancer and is still the third leading cause of cancer-related mortality worldwide. Accurate screening tools for early diagnosis and prediction of prognosis and precision treatment strategies are urgently required to accommodate the unmet medical needs of COAD management. We herein aimed to explore the significance of the microRNA (miR)-216a/growth differentiation factor 15 (GDF15) axis in terms of clinical value, tumor immunity, and potential mechanisms in COAD by using multi-omic analysis. The gene expression levels of miR-216a and GDF15 showed an increase in the COAD group compared to those of the normal group. The expression of miR-216a presented a negative correlation with GDF15 in COAD tumor tissue. The use of an in vitro luciferase reporter assay and bioinformatic prediction revealed that miR-216a-3p acted toward translational inhibition on GDF15 by targeting its 3'untranslated region (UTR) site. High miR-216a expression was associated with decreased overall survival (OS), while the high expression of GDF15 was associated with increased OS. Enriched type 1 T-helper (Th1), enriched regulatory T (Treg), enriched eosinophils, and decreased nature killer T-cells (NKTs) in COAD tumor tissue may play counteracting factors on the tumor-regulatory effects of miR-216a and GDF15. In addition, high GDF15 expression had associations with suppressed immunoinhibitory genes and negative correlations with the infiltration of macrophages and endothelial cells. The enrichment analysis revealed that GDF15 and its co-expression network may be implicated in mitochondrial organization, apoptosis signaling, and endoplasmic reticulum (ER) stress response. The Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Therapeutics Response Portal (CTRP) analysis identified that Gemcitabine acted as a precision treatment for COAD when GDF15 expression was low. This study supports the miR-216a/GDF15 axis as a diagnostic/prognostic panel for COAD, identifies Th1, Treg, eosinophils, and NKTs as counteracting factors, indicates potential relationships underlying immunomodulation, mitochondrial organization, apoptotic signaling, and ER stress and unveil Gemcitabine as a potential drug for the development of treatment strategy when combined with targeting GDF15.

Docosahexaenoic Acid Inhibits Cell Proliferation through a Suppression of c-Myc Protein in Pancreatic Ductal Adenocarcinoma Cells.

Treatment of pancreatic cancer by inhibiting the aberrant activation of the survival signaling pathways has received considerable attention. We investigated the probable action of DHA on the suppression of cell proliferation in human pancreatic ductal adenocarcinoma (PDAC) cells. Our results demonstrated that DHA dose-dependently inhibited cell proliferation through an induction of cell cycle arrest in human PDAC cells. DHA suppressed the expression of phosphorylated-Rb (p-Rb), cyclin D1, cyclin E, cyclin A, E2F1 and c-Myc proteins. Blocking the activation of STAT3 signaling pathway led to an inactivation of CAMKII and increased phosphorylation of c-Myc (T58) protein accompanied with decreased expression of c-Myc protein. Treatment of DHA effectively inhibited cell survival through decreased phosphorylation levels of EGFR, STAT3 and CAMKII proteins. The mechanisms of action were associated with increased phosphorylation levels of c-Myc (T58) and instability of c-Myc proteins. DHA inhibited cell survival through an increased GSSG/GSH ratio and oxidative stress level in HPAF-II cells. DHA induced cell apoptosis through increased expression of Bax, c-caspase 3 and c-PARP proteins in HPAF-II cells. Moreover, treatment of DHA significantly inhibited nucleotide synthesis. In conclusion, DHA might significantly suppress the proliferation of PDAC cells and therefore have potential as an anti-cancer therapeutic agent.

Using Gold-Nanorod-Filled Mesoporous Silica Nanobeads for Enhanced Radiotherapy of Oral Squamous Carcinoma.

Radiotherapy (RT), in combination with surgery, is an essential treatment strategy for oral cancer. Although irradiation provides effective control over tumor growth, the surrounding normal tissues are almost inevitably affected. With further understanding of the molecular mechanisms involved in radiation response and recent advances in nanotechnology, using gold nanoparticles as a radiosensitizer provides the preferential sensitization of tumor cells to radiation and minimizes normal tissue damage. Herein, we developed gold nano-sesame-beads (GNSbs), a gold-nanorod-seeded mesoporous silica nanoparticle, as a novel radioenhancer to achieve radiotherapy with a higher therapeutic index. GNSbs in combination with 2 Gy irradiation effectively enhanced the cytotoxic activity CAL-27 cells. The well-designed structure of GNSbs showed preferential cellular uptake by CAL-27 cells at 24 h after incubation. Gold nanorods with high density modified on mesoporous silica nanoparticles resulted in significant reactive oxygen species (ROS) formation after irradiation exposure compared with irradiation alone. Furthermore, GNSbs and irradiation induced more prominent DNA double-strand breaks and G2/M phase arrest in CAL-27 than those in L929. In animal studies, radiotherapy using GNSbs as a radiosensitizer showed significant suppression of tumor growth in an orthotopic model of oral cancer. These results demonstrate that using GNSbs as a radiosensitizer could possess clinical potential for the treatment of oral squamous carcinoma.

A Rapid and Feasible 1H-NMR Quantification Method of Ephedrine Alkaloids in Ephedra Herbal Preparations.

A highly specific and sensitive proton nuclear magnetic resonance (1H-NMR) method has been developed for the quantification of ephedrine alkaloid derivatives in Ephedra herbal commercial prescriptions. At the region of δ 4.0 to 5.0 ppm in the 1H NMR spectrum, the characteristic signals are separated well from each other, and six analogues in total, methylephedrine (ME), ephedrine (EP), norephedrine (NE), norpseudoephedrine (NP), pseudoephedrine (PE), and methylpseudoephedrine (MP) could be identified. The quantities of these compounds are calculated by the relative ratio of the integral values of the target peak for each compound to the known concentrations of the internal standard anthracene. The present method allows for a rapid and simple quantification of ephedrine alkaloid derivatives in Ephedra-related commercial prescriptions without any preliminary purification steps and standard compounds, and accordingly it can be a powerful tool to verify different Ephedra species. In comparison to conventional chromatographic methods, the advantages of this method include the fact that no standard compounds are required, the quantification can be directly performed on the crude extracts, a better selectivity for various ephedrine alkaloid derivatives, and the fact that a very significant time-gain may be achieved.

Identification of Hub Genes Associated With Development of Head and Neck Squamous Cell Carcinoma by Integrated Bioinformatics Analysis.

Improved insight into the molecular mechanisms of head and neck squamous cell carcinoma (HNSCC) is required to predict prognosis and develop a new therapeutic strategy for targeted genes. The aim of this study is to identify significant genes associated with HNSCC and to further analyze its prognostic significance. In our study, the cancer genome atlas (TCGA) HNSCC database and the gene expression profiles of GSE6631 from the Gene Expression Omnibus (GEO) were used to explore the differential co-expression genes in HNSCC compared with normal tissues. A total of 29 differential co-expression genes were screened out by Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis methods. As suggested in functional annotation analysis using the R clusterProfiler package, these genes were mainly enriched in epidermis development and differentiation (biological process), apical plasma membrane and cell-cell junction (cellular component), and enzyme inhibitor activity (molecular function). Furthermore, in a protein-protein interaction (PPI) network containing 21 nodes and 25 edges, the ten hub genes (S100A8, S100A9, IL1RN, CSTA, ANXA1, KRT4, TGM3, SCEL, PPL, and PSCA) were identified using the CytoHubba plugin of Cytoscape. The expression of the ten hub genes were all downregulated in HNSCC tissues compared with normal tissues. Based on survival analysis, the lower expression of CSTA was associated with worse overall survival (OS) in patients with HNSCC. Finally, the protein level of CSTA, which was validated by the Human Protein Atlas (HPA) database, was down-regulated consistently with mRNA levels in head and neck cancer samples. In summary, our study demonstrated that a survival-related gene is highly correlated with head and neck cancer development. Thus, CSTA may play important roles in the progression of head and neck cancer and serve as a potential biomarker for future diagnosis and treatment.

Changes in hot flash experiences and related factors in women with breast cancer.

OBJECTIVE: Taiwanese women are younger than women in western countries when diagnosed with breast cancer, and many of them are still menstruating. One of many distressing side effects reported by premenopausal women treated for breast cancer are hot flashes (HFs). The purposes of this study were to identify: (1) the trajectories of hot flash (HF) occurrence, frequency, and interference and (2) potential factors associated with HF changes. METHODS: Peri- or premenopausal women newly diagnosed with breast cancer scheduled to receive chemotherapy and hormonal therapy were enrolled. HF frequency, HF interference, and other symptoms were measured six times from prechemotherapy to 24 months after chemotherapy. Data were analyzed using hierarchical linear modeling. RESULTS: A total of 90 women were eligible for the study. The prechemotherapy occurrence rate of HFs was 7.9%, but rapidly increased to 42.5% immediately after chemotherapy. The change curve of HF frequency and interference appeared quadratic, increasing first and slightly decreasing later. At any time point, increased body mass index (BMI) was associated with both higher HF frequency (P = 0.020) and HF interference (P = 0.002), whereas anxiety (P < 0.001) and loss of sexual desire (P = 0.038) were associated with higher HF interference. Six months after completing chemotherapy, premenopausal women reported significantly higher HF frequency than perimenopausal women (P = 0.041). CONCLUSION: A significant proportion of pre- and perimenopausal women experienced HFs after receiving breast cancer treatment. Our findings on HF trajectories can educate patients newly diagnosed with breast cancer. Special attention should be paid to those with increased body mass index changes and those still regularly menstruating.