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Hung-Jin Huang,1,2 Olga A Kraevaya,3,4 Ilya I Voronov,4 Pavel A Troshin,3,4 Shan-hui Hsu1,2,5 1Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan; 2Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan; 3Skolkovo Institute of Science and Technology, Moscow, Russian Federation; 4Institute for Problems of Chemical Physics of Russian Academy of Sciences, Chernogolovka, Russian Federation; 5Research and Development Center for Medical Devices, National Taiwan University, Taipei, TaiwanCorrespondence: Shan-hui HsuInstitute of Polymer Science and Engineering, National Taiwan University, No. 1, Sec. 4 Roosevelt Road, Taipei 10617, TaiwanTel +886-2-3366-5313Fax +886-2-3366-5237Email shhsu@ntu.edu.twPavel A TroshinInstitute for Problems of Chemical Physics of Russian Academy of Sciences, Chernogolovka 142432, Russian FederationTel +7 496522-1418Fax +7 496515-5420Email troshin2003@inbox.ruBackground: Nanotechnology-based strategies in the treatment of cancer have potential advantages because of the favorable delivery of nanoparticles into tumors through porous vasculature.Materials and Methods: In the current study, we synthesized a series of water-soluble fullerene derivatives and observed their anti-tumor effects on human lung carcinoma A549 cell lines. The quantitative structure–activity relationship (QSAR) modeling was employed to investigate the relationship between anticancer effects and descriptors relevant to peculiarities of molecular structures of fullerene derivatives.Results: In the QSAR regression model, the evaluation results revealed that the determination coefficient r2 and leave-one-out cross-validation q2 for the recommended QSAR model were 0.9966 and 0.9246, respectively, indicating the reliability of the results. The molecular modeling showed that the lack of chlorine atom and a lower number of aliphatic single bonds in saturated hydrocarbon chains may be positively correlated with the lung cancer cytotoxicity of fullerene derivatives. Synthesized water-soluble fullerene derivatives have potential functional groups to inhibit the proliferation of lung cancer cells.Conclusion: The guidelines obtained from the QSAR model might strongly facilitate the rational design of potential fullerene-based drug candidates for lung cancer therapy in the future.Keywords: water-soluble fullerene derivatives, non-small cell lung cancer, cytotoxicity, machine learning, QSAR

Fai Lam,1–4 Chun-Chuan Shih,5 Ta-Liang Chen,4,6 Chao-Shun Lin,2–4 Hsiao-Ju Huang,7 Chun-Chieh Yeh,8,9 Yu-Chen Huang,10,11 Hung-Yi Chiou,1,* Chien-Chang Liao2–4,11,12,* 1School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan; 2Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan; 3Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan; 4Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 5School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan; 6Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 7Devision of Chinese Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan; 8Department of Surgery, China Medical University Hospital, Taichung, Taiwan; 9Department of Surgery, University of Illinois, Chicago, IL, USA; 10Department of Dermatology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 11Research Center of Big Data and Meta-Analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 12School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Chien-Chang LiaoDepartment of Anesthesiology, Taipei Medical University Hospital, Taipei 110, TaiwanTel +886-2-27372181 ext. 8310Fax +886-2-27367344Email jacky48863027@yahoo.com.twObjective: Urticaria is a mast cell-related disease caused severe itching and the lifetime prevalence of urticaria is about 20% in general population. Our purpose is to evaluate risk of urticaria in geriatric stroke patients received influenza vaccination (IV).Methods: In a cohort of 192,728 patients with newly diagnosed stroke aged over 65 years obtained from 23 million people in Taiwan’s National Health Insurance between 2000 and 2008, we identified 9890 stroke patients who received IV and 9890 propensity score-matched stroke patients who did not receive IV. Controlling for immortal time bias, both the IV and non-IV groups were followed for one year. Urticaria events were identified during the follow-up period. We calculated the adjusted rate ratios (RRs) and 95% confidence intervals (CIs) of the one-year risk of urticaria associated with IV.Results: During the follow-up period of one year, stroke patients with IV had a significantly higher risk of urticaria compared with non-IV stroke patients (RR 1.81, 95% CI 1.47–2.23). An increased risk of urticaria in stroke patients with IV was noted in both sexes, patients 65–84 years of age, patients with comorbid medical conditions, and various time intervals of follow-up. Vaccinated stroke patients with hemorrhage (RR 4.00, 95% CI 1.76–9.10) and those who received intensive care (RR 5.14, 95% CI 2.32–11.4) had a very high risk of urticaria compared with those without IV.Conclusion: Receiving IV may be associated with an increased risk of urticaria in stroke patients. We could not infer the causality from the current results because of this study’s limitations. Future investigations are needed to evaluate the possible mechanism underlying the association between IV and urticaria.Keywords: urticaria, stroke, influenza vaccination

Huilan Liu,* Huijuan Huang,* Boheng Li, Dong Wu, Fengmei Wang, Xiao hua Zheng, Qingxia Chen, Bifang Wu, Xiaojie FanDepartment of Obstetrics and Gynecology, East Hospital, Xiamen University, Fuzhou, Fujian, People’s Republic of China*These authors contributed equally to this workPurpose: The goal of this study was to investigate the anti-osteoporosis effect of extra virgin olive oil (EVOO) in vivo, and explore its antioxidant, anti-inflammatory properties in Sprague Dawley rats and its anticancer properties in patients.Materials and methods: A total of 120 healthy female Sprague Dawley rats aged 6 months were divided into four groups: 1) sham-operated control (Sham group, n=30); 2) ovariectomized (OVX group, n=30); 3) ovariectomized rats supplemented with EVOO (OVX + Olive, n=30); 4) ovariectomized rats supplemented with estrogen (OVX + E2, n=30). EVOO and estrogen were administered by oral gavage at a dose of 1 mL/100 g weight on a daily basis for 12 consecutive weeks. Twelve weeks later blood samples were obtained to detect the levels of calcium, alkaline phosphatase, phosphorus, interleukin-6 (IL-6), malonyldialdehyde (MDA), and nitrate content. Dual energy X-ray absorptiometer measured bone mineral density (BMD) of ovariectomized Sprague Dawley rats that had been fed olive oil for 3 months. Blood samples from patients, who regularly consumed olive oil over a 1 year period were also used to measure carbohydrate antigen 125, carcino-embryonic antigen, α-fetoprotein, and carbohydrate antigen 19-9 levels. BMD of lumbar spine and left femur was also evaluated by dual energy X-ray absorptiometry.Results: Animal experiments showed that EVOO significantly increased BMD and decreased phosphatase, alkaline phosphatase, IL-6, MDA, and nitrate levels. However, it had no significant effect on the Ca2+ level. In clinical follow-up, EVOO also improved patient BMD levels on L3, L4, and left femoral neck, and reduced carbohydrate antigen 125, α-fetoprotein, and carcino-embryonic antigen levels. But it had no significant effect on the carbohydrate antigen 19-9 level.Conclusion: EVOO illustrated significant anti-osteoporosis, antioxidant, anti-inflammatory, and anticancer properties in vivo. However, further studies are required to determine the active component(s) responsible for these effects.Keywords: olive oil, prevention, treatment, osteoporosis, artificial menopause

Background: Constitutively activated nuclear factor kappa B (NFkappaB) contributes to the development of cancer by regulating the expression of genes involved in cell survival, metastasis, and angiogenesis. The authors have demonstrated that MEKK3 plays a critical role in cytokine-mediated NFkappaB activation, and that stable expression of MEKK3 in cultured cells leads to increased NFkappaB activity.Methods: MEKK3 expression in ovarian cancer cells or tumors was assessed by Western blotting and real-time polymerase chain reaction. NFkappaB activities were analyzed by electrophoretic mobility shift assay and luciferase reporter assays. Western blot analysis for the survival factors were also performed and correlated with MEKK3 and NFkappaB activities. Cell survival assays were used to determine the sensitivity of ovarian cancer cells to various chemotherapeutic agents.Results: The authors found that 63% of the ovarian cancers had higher MEKK3 expression than the normal ovarian epithelial cells. Ovarian cancers with high MEKK3 showed correspondingly high IkappaB kinase and NFkappaB activity. Moreover, MEKK3 coimmunoprecipitated with Akt and cooperated with Akt to synergistically activate NFkappaB. Consistent with increased MEKK3 and NFkappaB activity in ovarian cancers, Bcl-2, Bcl-xL, survivin, and X-linked inhibitor of apoptosis levels were increased, which correlated with increased resistance to chemotherapeutic agents. Knockdown of MEKK3 with small interfering RNA significantly increased cancer cell sensitivity to paclitaxel.Conclusions: MEKK3 may be aberrantly expressed in ovarian cancers and plays an important role in tumors with constitutively activated NFkappaB. [ABSTRACT FROM AUTHOR]

Objective: Delivery-related levator avulsion can cause pelvic floor dysfunction. We compared agreement between tomographic ultrasound and magnetic resonance-based models for the detection of levator defects. Study Design: Sixty-nine Chinese women with pelvic organ prolapse were assessed prospectively by 3-dimensional ultrasound scans and magnetic resonance imaging. Levator-urethra gap (LUG), levator-symphysis gap (LSG), and puborectalis attachment width were measured offline with state-of-the-art software. Interobserver variability and agreement between the 2 methods were determined. Results: Interobserver repeatability was moderate-to-excellent for all parameters that were measured with both methods and agreement between methods in diagnosing levator avulsion. LUG and LSG measurements were significantly higher in women with a levator avulsion. With a diagnosis of complete levator avulsion, receiver operating characteristics analysis suggested a cutoff of 23.65 mm for LUG and 28.7 mm for LSG. Conclusion: Levator avulsion can be diagnosed reliably by tomographic ultrasound scanning and magnetic resonance imaging evaluation, and linear measures, such as LSG and LUG, can be proxy measurements for avulsion. [ABSTRACT FROM AUTHOR]

Insect oviposition secretions play crucial roles during the reproductive process, yet systematic studies on their structural characterization and protein compositions remain limited. This study investigated the oviposition secretions of three major rice pests: the brown planthopper (Nilaparvata lugens, BPH), small brown planthopper (Laodelphax striatella, SBPH), and white-backed planthopper (Sogatella furcifera, WBPH). Ultrastructural observation revealed differences in the oviposition secretions of them. The eggs of BPH and SBPH were adhered to rice tissue by abundant secretions, while WBPH eggs were embedded deeper within the leaf sheath with less secretions. Proteomic analysis identified 111, 98, and 66 oviposition secretion proteins (OSPs) in BPH, SBPH, and WBPH, respectively. 4 common protein subgroups were shared among them, along with varying numbers of shared subgroups between species pairs. Notably, the majority of OSPs were exclusively found in one species, indicating the existence of both similar and specialized functions unique to each planthopper species. The functions of 4 uncharacterized OSPs (Nl.chr07.0363, Nl.chr12.078, Nl.chr11.716, Nl.scaffold.0714) that were uniquely identified in the BPH were studied by maternal RNAi. Downregulation of each of these 4 protein-coding genes led to a significant decrease in egg production and hatchability. Moreover, knockdown of Nl.chr12.078 or Nl.chr07.0363 also disrupt the secretory function of the lateral oviduct. In conclusion, this study provides insights into the structural characteristics and protein components of the oviposition secretions of BPH, SBPH, and WBPH, which could serve as potential targets for RNAi-based pest control and lay a foundation for future studies on insect-plant interactions mediated by oviposition secretions., (Copyright © 2024. Published by Elsevier Ltd.)

The identification of sex chromosomes is fundamental for exploring the mechanism and evolution of sex determination. Platichthys stellatus , a species exhibiting clear sexual dimorphism and homomorphic chromosome pairs, has received limited research concerning its sex determination mechanisms. Clarifying the sex chromosome of P. stellatus will enhance our understanding of sex chromosome evolution in Pleuronectiformes. This study employed whole-genome resequencing to investigate the sex chromosome and sex determination system in P. stellatus . Notably, Chr23 was identified as the sex chromosome in P. stellatus , with the sex-determining region (SDR) occupying 48.1% of the chromosome and featuring an XX/XY system. Sex chromosome turnover was observed within Pleuronectiformes, with P. stellatus , Verasper variegatus , and Hippoglossus hippoglossus sharing a common ancestral karyotype. No inversions were detected within the SDR of P. stellatus , although chromosomal rearrangements between sex chromosomes and autosomes were identified. Additionally, a sex-specific marker for P. stellatus was ascertained, enabling genetic sex identification, with significant implications for improving breeding programs and aquaculture practices.

Liquid-to-solid phase transition of proteins with prion-like domains (PLDs) has been associated with neurodegenerative diseases and aging. High protein concentration is one important aspect triggering the transition; however, several prion-like proteins, including fibrillarin (FBL), an important phase-separated protein in the nucleolus for pre-rRNA processing, show relatively high expression levels in certain cells, especially cancer cells, without obvious phase transitions and growth arrest. How cells maintain prion-like protein proteostasis is still unknown. Here, we attempt to answer the question, with FBL as an example. We find that lncRNA DNAJC3-AS1 can buffer the behavior of FBL condensation and maintain the state and function of fibrillar component/dense fibrillar component (FC/DFC) units in human cell lines through two mechanisms, not only facilitating FBL condensation but also inhibiting excessive aggregation by binding multiple PLDs and partially blocking their interactions. We propose that lncRNAs could supply buffered systems to sustain functional phase states of prion-like proteins., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Shrimp acute hepatopancreatic necrosis disease (AHPND) is one of the most devastating diseases to impact the global shrimp farming industry, with a mortality rate of 70 %-100 %. The key virulence factors are a pair of Photorhabdus insect-related (Pir)-like toxins, PirA vp and PirB vp . In this study, by using an in vitro transcription and translation assay, we first confirmed that the quorum sensing transcriptional regulator AphB vp could trigger the expression of its downstream genes after binding to the AphB vp binding sequence in the promoter region of the pirA vp /pirB vp operon. Next, we showed that AphB vp was essential for the expression of these toxins by using an aphB vp -deletion mutant (ΔaphB vp ) derived from the AHPND-causing Vibrio parahaemolyticus. Lastly, we discovered that the expression levels of PirA vp and PirB vp were up-regulated under acidic conditions (pH 4.5), and further showed that an acidic environment promoted the binding of AphB vp to the pirAB vp promoter. We speculate that this was because the acidic environment favored the formation of AphB vp tetramers, which is important for binding to DNA. Taken together, these findings improve our understanding of the gene regulatory mechanisms of pirA vp and pirB vp , and suggest that the pH value of the environment might affect the virulence of AHPND-causing V. parahaemolyticus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Ovarian clear cell carcinoma (OCCC) has a disproportionately high incidence among women in East Asia. Patients diagnosed with OCCC tend to experience worse clinical outcomes than those with high-grade serous carcinoma (HGSC) at advanced stages. The unfavorable prognosis of OCCC can be partly attributed to its frequent resistance to conventional chemotherapy. Within a precision medicine framework, we sought to provide a comprehensive molecular characterization of OCCC using whole-exome sequencing to uncover potential molecular targets that may inform novel therapeutic strategies., Methods: We performed whole-exome sequencing analysis on tumor-normal paired samples from 102 OCCC patients. This comprehensive genomic characterization of a substantial cohort of OCCC specimens was coupled with an analysis of clonal progression., Results: On analyzing 102 OCCC samples, ARID1A (67%) and PIK3CA (49%) emerged as the most frequently mutated driver genes. We identified tier 1 or 2 clinically actionable molecular targets in 40% of cases. This included DNA mismatch repair deficiency (n = 1), as well as BRCA2 (n = 1), PIK3CA (n = 36), KRAS G12C (n = 1), and ATM (n = 4) mutations. Furthermore, 45% of OCCC samples displayed ARID1A biallelic loss. Interestingly, we identified previously unreported mutations in the 5' untranslated region of the TERT gene that harbored an adverse prognostic significance. Clock-like mutational processes and activated APOBECs were major drivers of somatic point mutations. Mutations arising from DNA mismatch repair deficiency were uncommon. Reconstruction of clonal evolution revealed that early genetic events likely driving tumorigenesis included mutations in the ARID1A, PIK3CA, TERT, KRAS, and TP53 genes., Conclusions: Our study provides a comprehensive characterization of the genomic landscape and clonal evolution in OCCC within a substantial cohort. These findings unveil potentially actionable molecular alterations that could be leveraged to develop targeted therapies., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Institutional Review Board of the Chang Gung Memorial Hospital (reference number: 202000143B0). Given the retrospective nature of the analysis, the requirement for informed consent was waived. Consent for publication All authors have provided their consent for the publication of this manuscript. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The brown planthopper (BPH) is the most destructive insect pest in rice. Through a stylet, BPH secretes a plethora of salivary proteins into rice phloem cells as a crucial step of infestation. However, how various salivary proteins function in rice cells to promote insect infestation is poorly understood. Among them, one of the salivary proteins is predicted to be a carbonic anhydrase (Nilaparvata lugens carbonic anhydrase [NlCA]). The survival rate of the NlCA-RNA interference (RNAi) BPH insects was extremely low on rice, indicating a vital role of this salivary protein in BPH infestation. We generated NlCA transgenic rice plants and found that NlCA expressed in rice plants could restore the ability of NlCA-RNAi BPH to survive on rice. Next, we produced rice plants expressing the ratiometric pH sensor pHusion and found that NlCA-RNAi BPH induced rapid intracellular acidification of rice cells during feeding. Further analysis revealed that both NlCA-RNAi BPH feeding and artificial lowering of intracellular pH activated plant defense responses and that NlCA-mediated intracellular pH stabilization is linked to diminished defense responses, including reduced callose deposition at the phloem sieve plates and suppressed defense gene expression. Given the importance of pH homeostasis across the kingdoms of life, discovery of NlCA-mediated intracellular pH modulation uncovered a new dimension in the interaction between plants and piercing/sucking insect pests. The crucial role of NlCA for BPH infestation of rice suggests that NlCA is a promising target for chemical or trans-kingdom RNAi-based inactivation for BPH control strategies in plants., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)