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Kuo-Feng Hua,1,2,* Hsien-Ta Hsu,3,4,* May-Shu Huang,5,6 Hsiao-Wen Chiu,1 Wei-Ting Wong,1 Chien-Hsiu Peng,1 Yu-Bei Lin,1 Ann Chen,7 Chien-Chun Wang,8,9 Chung-Hua Hsu,10,11 Chun-Hsien Wu,12 Wen-Yu Lin,1,12 Chen-Lung Ho,13 Lan-Hui Li14 1Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan; 2Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; 3Division of Neurosurgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 4School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan; 5Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 6Department of Laboratory Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 7Department of Pathology, Hualien Tzu Chi Hospital, Hualien, Taiwan; 8Infectious Disease Division, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, Taiwan; 9Kunming Prevention and Control Center, Taipei City Hospital, Taipei, Taiwan; 10Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, Taiwan; 11Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 12Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 13Division of Wood Cellulose, Taiwan Forestry Research Institute, Taipei, Taiwan; 14Department of Laboratory Medicine, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Lan-Hui Li, Department of Laboratory Medicine, Linsen, Chinese Medicine and Kunming Branch, Taipei City Hospital, 100, Kunming Street, Wanhua District, Taipei City, 108203, Taiwan, Tel +886-2-23703739 # 1438, Fax +886-2-23885259, Email A1525@tpech.gov.twPurpose: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, crucial in infectious and inflammatory diseases by regulating IL-1β, presents a target for disease management. Neisseria gonorrhoeae causes gonorrhea in over 87 million people annually, with previous research revealing NLRP3 inflammasome activation in infected macrophages. No natural products have been reported to counteract this activation. Exploring honokiol, a phenolic compound from Chinese herbal medicine, we investigated its impact on NLRP3 inflammasome activation in N. gonorrhoeae-infected macrophages.Methods: Honokiol’s impact on the protein expression of pro-inflammatory mediators was analyzed using ELISA and Western blotting. The generation of intracellular H2O2 and mitochondrial reactive oxygen species (ROS) was detected through specific fluorescent probes (CM-H2DCFDA and MitoSOX, respectively) and analyzed by flow cytometry. Mitochondrial membrane integrity was assessed using specific fluorescent probes (MitoTracker and DiOC2(3)) and analyzed by flow cytometry. Additionally, the effect of honokiol on the viability of N. gonorrhoeae was examined through an in vitro colony-forming units assay.Results: Honokiol effectively inhibits caspase-1, caspase-11 and GSDMD activation and reduces the extracellular release of IL-1β, NLRP3, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) in N. gonorrhoeae-infected macrophages. Detailed investigations have demonstrated that honokiol lowers the production of H2O2 and the phosphorylation of ERK1/2 in N. gonorrhoeae-infected macrophages. Importantly, the phosphorylation of JNK1/2 and p38 and the activation of NF-κB remain unaffected. Moreover, honokiol reduces the N. gonorrhoeae-mediated generation of reactive oxygen species within the mitochondria, preserving their integrity. Additionally, honokiol suppresses the expression of the pro-inflammatory mediator IL-6 and inducible nitric oxide synthase induced by N. gonorrhoeae independently of NLRP3. Impressively, honokiol exhibits in vitro anti-gonococcal activity against N. gonorrhoeae.Conclusion: Honokiol inhibits the NLRP3 inflammasome in N. gonorrhoeae-infected macrophages and holds great promise for further development as an active ingredient in the prevention and treatment of symptoms associated with gonorrhea.Keywords: Neisseria gonorrhoeae, honokiol, NLRP3 inflammasome, mitochondria, bactericiide

Hsiao-Mei Hsu,1 Hsin-I Tsai,2– 4 Wei-Chen Lee,4,5 Chih-Chi Wang,6,7 Ming-Chin Yu,3,4,8 Shi-Ming Lin,4,9 Chun-Yen Lin,4,9 Chi-Huan Wu,4,9 Chao-Wei Lee3– 5 1Department of Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Department of Anesthesiology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 3Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan; 4College of Medicine, Chang Gung University, Taoyuan, Taiwan; 5Division of General Surgery, Department of Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 6Division of General Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 7Division of General Surgery, Department of Surgery, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 8Department of Surgery, New Taipei Municipal Tu-Cheng Hospital (Built and Operated by Chang Gung Medical Foundation), New Taipei City, Taiwan; 9Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, TaiwanCorrespondence: Chao-Wei Lee, Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Guishan, No. 5, Fuxing St., Guishan District, Taoyuan City, 33305, Taiwan, Tel +886-975366192, Email alanchaoweilee@hotmail.comAbstract: Surgical resection remains one of the most effective curative therapies for HCC. However, the majority of patients have advanced unresectable diseases upon presentation. It is of paramount importance to raise the resectability of patients with HCC. The remarkable objective response rate reported by Phase III IMbrave150 trial has led to the concept of “Atezo/Bev followed by curative conversion (ABC conversion)” for initially unresectable HCC. With this revolutionary treatment strategy, the concept of surgical resection for HCC should be amended. The current opinion illustrated three extended surgical concepts, which could be integrated into clinical practice in the era of immune checkpoint inhibitors (ICI).Keywords: hepatocellular carcinoma, liver resection, surgery, immune checkpoint inhibitors, immunotherapy

Chih-Hsun Wu,1,2 Wei-Han Chou,3 Yi-Hsun Long,2 Hao-Han Yang,1 Tung Lin,1 Chi-Cheng Yang,1,4 Wei-Zen Sun,3 Chih-Cheng Chen,5 Chih-Peng Lin3 1Department of Psychology, National Chengchi University, Taipei, Taiwan; 2Clinical Psychology Center, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Anesthesiology, National Taiwan University Hospital, Taipei, Taiwan; 4Holistic Mental Health Center, Taipei City Hospital, Taipei, Taiwan; 5Institute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanCorrespondence: Chih-Peng Lin, Department of Anesthesiology, National Taiwan University Hospital, 7 Chung Shan S. Road, Taipei, 100225, Taiwan, Tel +886 2 23123456 #262158, Fax +886 2 23415736, Email cplin0123@gmail.comPurpose: People with pain problems are highly vulnerable to cultural disparities, and it is imperative to reduce these inequalities. This cross-sectional study aimed to develop a culturally sensitive Chronic Pain Cognition Scale (CPCS) for Chinese-/Chinese dialect-speaking populations and investigate its psychometric properties.Patients and Methods: Adult patients with chronic low back pain or chronic neck pain who visited pain clinics at a medical center in northern Taiwan were enrolled. Participants completed the demographic, intensity of pain, and two other related sensations, “Sng (痠)” and “Ma (麻)”, often reported in Chinese-speaking populations, CPCS, Chronic Pain Acceptance Questionnaire-8, and Pain Self-Efficacy Questionnaire.Results: 200 patients were included. Patients’ mean age was 64.84 ± 14.33, 126 (63.0%) were female, and 83 (41.5%) had 13+ years of education. The average duration of pain was 77.25 ± 97.46 months, the intensity of pain was 6.04 ± 2.50, Ma was 3.43 ± 3.24, and Sng was 4.54 ± 3.14. The CPCS comprised four factors: pain impact (how pain impact one’s life), losing face (how one being disrespected due to pain), helplessness, and avoidance, with good structural validity and adequate reliability (Cronbach α, 0.60– 0.81) and satisfactory criterion-related validity. Moreover, losing face, an essential concept in Chinese relationalism, was significantly related to pain, Sng, and Ma (r = 0.19, 0.15 and 0.16), but not to pain acceptance or self-efficacy, indicating a culturally specific element in pain measurement.Conclusion: The CPCS has good psychometric properties and is suitable for evaluating chronic pain in the clinical setting, and might be generalizable to other Chinese-/Chinese dialect-speaking populations.Keywords: low back pain, neck pain, pain impact, losing face, helplessness, avoidance

Yu-Syuan Wei,1 Yu-Liang Chen,2 Wei-Yun Li,1 Ya-Yi Yang,3 Sung-Jan Lin,4– 6 Ching-Ho Wu,7 Jiue-In Yang,8 Tse-En Wang,1 Jiashing Yu,2 Pei-Shiue Tsai1,3,4 1Graduate Institute of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; 2Department of Chemical Engineering, College of Engineering, National Taiwan University, Taipei, 106, Taiwan; 3Department of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; 4Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, 10617, Taiwan; 5Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, 10051, Taiwan; 6Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei, 10002, Taiwan; 7Graduate Institute of Veterinary Clinical Science, School of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; 8Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, 10617, TaiwanCorrespondence: Jiashing Yu, Department of Chemical Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Daan District, Taipei, 10617, Taiwan, Tel +886 2 33669477, Email jiayu@ntu.edu.tw Pei-Shiue Tsai, Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Daan District, Taipei, 10617, Taiwan, Tel +886 2 33661290, Fax +886 2 23661475, Email psjasontsai@ntu.edu.twIntroduction: Cisplatin, a commonly used anticancer compound, exhibits severe off-target organ toxicity. Due to its wide application in cancer treatment, the reduction of its damage to normal tissue is an imminent clinical need. Cisplatin-induced testicular oxidative stress and damage lead to male sub- or infertility. Despite earlier studies showing that the natural polyphenol extracts honokiol serve as the free radical scavenger that reduces the accumulation of intracellular free radicals, whether honokiol exhibits direct effects on the testis and sperm is unclear. Thus, the aim of the current study is to investigate the direct effects of honokiol on testicular recovery and sperm physiology.Methods: We encapsulated this polyphenol antioxidation compound into liposome-based nanoparticles (nHNK) and gave intraperitoneally to mice at a dosage of 5 mg/kg body mass every other day for consecutive 6 weeks.Results: We showed that nHNK promotes MDC1-53bp1-associated non-homologous DNA double-strand break repair signaling pathway that minimizes cisplatin-induced DNA damage. This positive effect restores spermatogenesis and allows the restructuring of the multi-spermatogenic layers in the testis. By reducing mitochondrial oxidative damage, nHNK also protects sperm mitochondrial structure and maintains both testicular and sperm ATP production. By a yet-to-identify mechanism, nHNK restores sperm calcium influx at the sperm midpiece and tail, which is essential for sperm hypermotility and their interaction with the oocyte.Discussion: Taken together, the nanoparticulated antioxidant counteracts cisplatin-induced male fertility defects and benefits patients undertaking cisplatin-based chemotherapy. These data may allow the reintroduction of cisplatin for systemic applications in patients at clinics with reduced testicular toxicity.Keywords: nanomedicine, antioxidant, cisplatin, reproduction, DNA repair, polyphenol

Yu-Feng Su,1– 3 Tai-Hsin Tsai,2– 4 Keng-Liang Kuo,2,4 Chieh-Hsin Wu,2,4 Cheng-Yu Tsai,1,2 Yen-Mou Lu,5 Shiuh-Lin Hwang,6 Pei-Chen Lin,7 Ann-Shung Lieu,2 Chih-Lung Lin,1,2,4 Chih-Hui Chang1,2,4 1Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 3Division of Neurosurgery, Department of Surgery, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; 4Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Orthopedics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 6Department of Spinal Surgery, Chi-Hsien Spine Hospital, Kaohsiung, Taiwan; 7Department of Oral Hygiene, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Chih-Hui Chang, Email chchang20@gmail.comBackground: The aim of this study was to investigate the learning curve of robotic spine surgery quantitatively with the well-described power law of practice.Methods: Kaohsiung Medical University Hospital set up a robotic spine surgery team by the neurosurgery department in 2013 and the orthopedic department joined the well-established team in 2014. A total of consecutive 150 cases received robotic assisted spinal surgery. The 150 cases, with 841 transpedicular screws were enrolled into 3 groups: the first 50 cases performed by neurosurgeons, the first 50 cases by orthopedic surgeons, and 50 cases by neurosurgeons after the orthopedic surgeons joined the team. The time per screw and accuracy by each group and individual surgeon were analyzed.Results: The time per screw for each group was 9.56 ± 4.19, 7.29 ± 3.64, and 8.74 ± 5.77 minutes, respectively, with p-value 0.0017. The accuracy was 99.6% (253/254), 99.5% (361/363), and 99.1% (222/224), respectively, with p-value 0.77. Though the first group took time significantly more on per screw placement but without significance on the nonlinear parallelism F-test. Analysis of 5 surgeons and their first 10 cases of short segment surgery showed the time per screw by each surgeon was 12.28 ± 5.21, 6.38 ± 1.54, 8.68 ± 3.10, 6.33 ± 1.90, and 6.73 ± 1.81 minutes. The first surgeon who initiated the robotic spine surgery took significantly more time per screw, and the nonlinear parallelism test also revealed only the first surgeon had a steeper learning curve.Conclusion: This is the first study to demonstrate that differences of learning curves between individual surgeons and teams. The roles of teamwork and the unmet needs due to lack of active perception are discussed.Keywords: human computer communication, human–robot collaboration, learning curve, robotic spine surgery, teamwork

Hao Lin,1 Wen-Hsin Chen,1 Chen-Hsuan Wu,1,2 Yu-Che Ou,3 Yu-Jen Chen,3 Ying-Yi Chen,1 Yu-Han Lin,4 Hung-Chun Fu1– 3 1Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Graduate Institute of Clinical Medical Sciences, Chang Gung University, Lin-Kou, Taiwan; 3Department of Obstetrics and Gynecology, Chia-Yi Chang Gung Memorial Hospital, Chia-Yi, Taiwan; 4Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Tainan, TaiwanCorrespondence: Hung-Chun FuDepartment of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta Pei Road, Niao Sung District, Kaohsiung City, Taiwan, Republic of ChinaTel +886 7 731712Fax +886 7 7322915Email allen133@adm.cgmh.org.twAim: To investigate whether the time interval between primary debulking surgery (PDS) and initiating adjuvant chemotherapy affects survival in patients with epithelial ovarian cancer (EOC).Methods: We retrospectively reviewed FIGO stage IIB to IV EOC patients who received PDS followed by adjuvant chemotherapy in our hospital between January 2008 and December 2016. The optimal cut-off time interval to chemotherapy related to survival was determined using the Contal and O’Quigley method and Cox hazard models. Cox regression analysis was used to identify the independent effect of time interval on survival.Results: A total of 152 patients were identified and divided into three groups based on the time interval between PDS and initiating adjuvant chemotherapy: early (< 23 days), intermediate (23– 43 days) and late (> 43 days). The intermediate group had a significantly better median progression-free survival (PFS, 35.5 months) compared to the early (20 months) and late (22.6 months) groups. After adjustments for confounding factors, time interval was still an independent variable affecting PFS. The intermediate group was associated with a better PFS compared with the early and late groups (hazard ratio 0.27, 95% CI 0.10– 0.83, p=0.002). There was no statistical significance in overall survival (OS) in univariate or multivariate analysis, although there was a trend towards better OS in the intermediate group.Conclusion: Our results provide evidence that the time interval from PDS to chemotherapy influences PFS in patients with advanced EOC. The optimal time to initiate chemotherapy was between 23 and 43 days, within 3– 6 weeks post-operatively. Initiating chemotherapy early (< 23 days) did not appear to benefit PFS.Keywords: time interval, chemotherapy, ovarian cancer

Chi-Huan Wu, Mu-Hsien Lee, Yung-Kuan Tsou, Wei Teng, Cheng-Hui Lin, Kai-Feng Sung, Nai-Jen Liu Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, TaiwanCorrespondence: Nai-Jen LiuDepartment of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, TaiwanTel +886-3-3281200 Ext 8108Fax +886-3-3272236Email launaijn.tw@yahoo.com.twPurpose: Self-expandable metal stents are used for malignant duodenal obstruction. Outcomes between stents placed above and below the papilla of Vater differ, and no study has investigated these differences. We evaluated the efficacy and adverse events of stent placement in these two locations and reported our experience with self-expandable metal stent placement in patients.Patients and Methods: We retrospectively analyzed the data of patients with unresectable metastatic cancers (n = 101), who underwent successful duodenal self-expandable metal stent placement between 2008 and 2018. Patients were divided into above and below the papilla of Vater groups. Patient demographics, technical and clinical outcomes, post-procedural morbidity, and stent patency were analyzed.Results: Overall, 71 and 30 patients had intestinal obstruction above (including the papilla itself) and below the papilla of Vater and underwent successful stenting. Common bile duct obstruction was more common in the above-papilla group. Procedure time was similar between the groups, if an appropriate endoscope could facilitate stent placement in the below-papilla group. Both groups achieved symptomatic relief. Median stent patency duration was not significantly different between the groups; three patients had severe gastrointestinal bleeding due to postoperative vascular-enteric fistula.Conclusion: Self-expandable metal stents can effectively relieve symptoms of duodenal obstructions located above and below the papilla of Vater. Duodenoscopes could facilitate stent placement if the obstruction is located below the papilla of Vater; if gastrointestinal bleeding occurs postoperatively, the possibility of vascular-enteric fistula formation should be considered.Keywords: enteric fistula, intestinal stricture, intestinal malignancy, bile duct obstruction, duodenoscope, gastrointestinal bleeding

Hong-Ping Li,1 Wen Su,2 Yang Shu,3 Xiao-Cui Yuan,1 Li-Xue Lin,1 Teng-Fei Hou,1 Hong-Chun Xiang,1 He Zhu,1 Xue-Fei Hu,1 Li Pan,1 Jing-Nan Wu,1 Xian-Fang Meng,1 Hui-Lin Pan,4 Cai-Hua Wu,1,2 Man Li11Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Acupuncture, Wuhan First Hospital, Wuhan, People’s Republic of China; 3Department of Central Laboratory, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, People’s Republic of China; 4Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAPurpose: We determined whether electroacupuncture (EA) reduces Netrin-1-induced myelinated primary afferent nerve fiber sprouting in the spinal cord and pain hypersensitivity associated with postherpetic neuralgia (PHN) through activation of μ-opioid receptors.Methods: PHN was induced by systemic injection of resiniferatoxin (RTX) in rats. Thirty-six days after RTX injection, a μ-opioid receptor antagonist, beta-funaltrexamine (β-FNA) or a κ-opioid receptor antagonist, nor Binaltorphimine (nor-BNI), was injected intrathecally 30 mins before EA, once every other day for 4 times. Mechanical allodynia was tested with von Frey filaments. The protein expression level of Netrin-1 and its receptors (DCC and UNC5H2) were quantified by using western blotting. The myelinated primary afferent nerve fiber sprouting was mapped with the transganglionic tracer cholera toxin B-subunit (CTB).Results: Treatment with 2 Hz EA at “Huantiao” (GB30) and “Yanglingquan” (GB34) decreased the mechanical allodynia at 22 days and the myelinated primary afferent nerve fiber preternatural sprouting into the lamina II of the spinal dorsal horn at 42 days after RTX injection. Also, treatment with 2 Hz EA reduced the protein levels of DCC and Netrin-1 and promoted the expression of UNC5H2 in the spinal dorsal horn 42 days after RTX injection. Furthermore, the μ-opioid receptor antagonist β-FNA, but not the κ-opioid receptor antagonist nor-BNI, reversed the effect of EA on neuropathic pain caused by RTX. In addition, morphine inhibited the Netrin-1 protein level induced by RTX in SH-SY5Y cells.Conclusions: Through activation of μ-opioid receptors, treatment with EA reduces the expression level of DCC and Netrin-1 and changes a growth-permissive environment in spinal dorsal horn into an inhibitory environment by increasing UNC5H2, thus decreasing RTX-caused primary afferent nerve sprouting in the spinal dorsal horn and neuropathic pain.Keywords: postherpetic neuralgia, analgesia, mechanical hyperalgesia, rat, μ-opioid receptors

Xiao-Cui Yuan,1 Qiang Wang,2 Wen Su,3 Hong-Ping Li,1 Cai-Hua Wu,3 Fang Gao,1 Hong-Chun Xiang,1 He Zhu,1 Li-Xue Lin,1 Xue-Fei Hu,1 Jie Cao,4 Jing-Jing Li,1 Man Li1 1Department of Neurobiology and Key Laboratory of Neurological Diseases of Ministry of Education, The Institute of Brain Research, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 2Department of Anesthesiology, First Affiliated Hospital of Xi’an JiaoTong University, Xi’an, People’s Republic of China; 3Department of Acupuncture, Wuhan First Hospital, Wuhan 430030, People’s Republic of China; 4Department of Neurology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China Purpose: Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, with chronic pain as its typical symptom. Although studies have shown that an activated peripheral CB2 receptor can reduce acute pain, whether the CB2 receptor is involved in electroacupuncture (EA) inhibiting chronic pain and the involved mechanism remains unclear. The aim of this study was to investigate whether EA may strengthen peripheral CB2 receptor-inhibited chronic pain in a mouse model of KOA. Materials and methods: KOA was induced by intra-articular injection of monosodium iodoacetate (MIA) into the left knee joint of mice. Thermal hyperalgesia was tested with the hot plate test, and mechanical allodynia was quantified using von Frey filaments. The expression of CB2 receptor and IL-1β were quantified by using immunofluorescence labeling. Results: EA treatment at 2 Hz+1 mA significantly increased the expression of CB2 receptor in fibroblasts and decreased the expression of IL-1β in the menisci compared with that in the KOA group. However, EA had no effect on the expression of IL-1β in CB2−/− mice. At 2 Hz+1 mA, EA significantly increased mechanical threshold, thermal latency, and weight borne after KOA modeling. However, knockout of the CB2 receptor blocked these effects of EA. After 2 Hz+1 mA treatment, EA significantly reduced the Osteoarthritis Research Society International (OARSI) score after KOA modeling. However, EA had no significant effect on the OARSI score in CB2−/− mice. Conclusion: EA reduced the expression of IL-1β by activating the CB2 receptor, thus inhibiting the chronic pain in the mouse model of KOA. Keywords: cannabinoid, acupuncture, inflammatory pain, IL-1β

Chih-Cheng Lai,1 Che-Hsiung Wu,2,3 Ya-Hui Wang,4 Cheng-Yi Wang,4 Vin-Cent Wu,5 Likwang Chen6 1Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Taiwan; 2Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan; 3School of Medicine, Tzu Chi University, Hualien, Zhunan, Taiwan; 4Medical Research Center, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; 5Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; 6Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan Objective: The aim of this study was to investigate the impact of COPD on the outcomes of patients with advanced chronic kidney disease (CKD).Patients and methods: All patients with advanced CKD from 2000 to 2010 were identified from the Taiwanese National Health Insurance Research Database. Associations between COPD and the risk of long-term dialysis and all-cause mortality were assessed.Results: A total of 33,399 advanced CKD patients were enrolled, of whom 31,536 did not have COPD (non-COPD group) and 1,863 had COPD (COPD group). The incidence of end-stage renal disease (ESRD) was higher for those with COPD than those without COPD (744.2 per 1,000 person-years vs 724.6 per 1,000 person-years, adjusted HR [aHR] 1.04; 95% CI 0.96–1.12). The cumulative incidence rates of ESRD were similar between the COPD and non-COPD groups (log-rank test, P=0.356). Overall, the patients with COPD had a higher risk of death than those without COPD (151.7 per 1,000 person-years vs 125.5 per 1,000 person-years, aHR 1.22; 95% CI 1.11–1.33). The cumulative mortality rate was higher in the COPD group than in the non-COPD group (log-rank test, P

Kou-Toung Chung,* Chih-Hsiang Hsu,* Ching-Lung Lin, Sheue-Er Wang, Chung-Hsin WuDepartment of Life Science, National Taiwan Normal University, Taipei, Taiwan*These authors contributed equally to this workAim: The present study investigated whether intraperitoneal treatment with the herbal formula B210 ([B210]; a herbal composition of Gastrodia elata and Cinnamomum cassia) can reduce snoring in aged rats. Also, we studied possible neural mechanisms involved in B210 treatment and subsequent reduced snoring in rats.Methods and result: We compared pressure and frequency of snoring, activities of phrenic nerve (PNA), activities of recurrent laryngeal nerve (RLNA) and activities of hypoglossal nerve (HNA), inspiratory time (TI) and expiratory time (TE) of PNA, and pre-inspiratory time (Pre-TI) of HNA in aged rats between sham and B210 treatment groups (30 mg/mL dissolved in DMSO). We found that aged rats that received B210 treatment had significantly reduced pressure and frequency of snoring than rats who received sham treatment. Also, we observed that aged rats that received B210 treatment had significantly increased PNA, RLNA, and HNA, extended TI and TE of PNA, and prolonged Pre-TI of HNA compared to rats that received sham treatment. In other words, B210 treatment may relieve snoring through modulating activities and breathing time of upper airway related nerves in aged rats.Conclusion: We suggested that the B210 might be a potential herbal formula for snoring remission.Keywords: Chinese herbal medicine, snoring remission, upper airway, phrenic nerve, recurrent laryngeal nerve, hypoglossal nerve

Chi-Huan Wu,1,2 Tsung-Hsing Chen,1–3 Chen-Ming Hsu,1,2 Ming-Yao Su,1,2 Cheng-Tang Chiu,1,2 Ren-Chin Wu,4 Cheng-Chou Lai5 1Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, 2Chang Gung University, College of Medicine, Taoyuan, 3Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, 4Department of Pathology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, 5Department of Colon and Rectal Surgery, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan Introduction: Linked-color imaging (LCI) is a recently developed system used in endoscopy. It creates clear and bright endoscopic images using short-wavelength, narrow-band laser light combined with white laser light. The illuminating light and signal processing emphasize slight color differences in abnormal regions that approximate the normal color of the mucosa. As a result, regions initially appearing red become a deeper shade of red, while regions originally appearing white become brighter, yet with natural tones. This process facilitates recognition of slight differences in the color of the mucosa and clarifies the boundaries of the mucosal pit. Aim: To determine whether LCI of the colon can improve the correlation between endoscopic findings and pathological diagnosis. Methods: Consecutive patients who underwent colonoscopy requiring polypectomy or removal by biopsy forceps if possible were recruited. Probable polyp histology was assessed by two endoscopists using the Narrow-band imaging International Colorectal Endoscopic (NICE) classification and LCI data. All detected polyps were sent to the pathology department for pathological diagnosis by two pathologists. Results: In total, 94 polyps were found in 43 patients. The sensitivity, specificity, positive predictive value, and negative predictive value for neoplastic lesion prediction (NICE type2/3) were 96.5%, 83.8%, 90.2%, and 93.9%, respectively. Conclusion: LCI combined with the NICE classification system is a powerful tool for predicting probable histology of colon polyps. Keywords: linked-color imaging, NICE classification, colon polyps, histology, sensitivity, specificity

Xue Shen,1 Tingting Li,1 Zhongyuan Chen,1 Yue Geng,1 Xiaoxue Xie,1 Shun Li,1,2 Hong Yang,1,2 Chunhui Wu,1,2 Yiyao Liu1,2 1Department of Biophysics, School of Life Science and Technology, 2Center for Information in Biology, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China Abstract: Cancer diagnosis and treatment represent an urgent medical need given the rising cancer incidence over the past few decades. Cancer theranostics, namely, the combination of diagnostics and therapeutics within a single agent, are being developed using various anticancer drug-, siRNA-, or inorganic materials-loaded nanocarriers. Herein, we demonstrate a strategy of encapsulating quantum dots, superparamagnetic Fe3O4 nanocrystals, and doxorubicin (DOX) into biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) polymeric nanocomposites using the double emulsion solvent evaporation method, followed by coupling to the amine group of polyethyleneimine premodified with polyethylene glycol-folic acid (PEI-PEG-FA [PPF]) segments and adsorption of vascular endothelial growth factor (VEGF)-targeted small hairpin RNA (shRNA). VEGF is important for tumor growth, progression, and metastasis. These drug-loaded luminescent/magnetic PLGA-based hybrid nanocomposites (LDM-PLGA/PPF/VEGF shRNA) were fabricated for tumor-specific targeting, drug/gene delivery, and cancer imaging. The data showed that LDM-PLGA/PPF/VEGF shRNA nanocomposites can codeliver DOX and VEGF shRNA into tumor cells and effectively suppress VEGF expression, exhibiting remarkable synergistic antitumor effects both in vitro and in vivo. The cell viability was ~14% when treated with LDM-PLGA/PPF/VEGF shRNA nanocomposites ([DOX] =25 µg/mL), and in vivo tumor growth data showed that the tumor volume decreased by 81% compared with the saline group at 21 days postinjection. Magnetic resonance and fluorescence imaging data revealed that the luminescent/magnetic hybrid nanocomposites may also be used as an efficient nanoprobe for enhanced T2-weighted magnetic resonance and fluorescence imaging in vitro and in vivo. The present work validates the great potential of the developed multifunctional LDM-PLGA/PPF/VEGF shRNA nanocomposites as effective theranostic agents through the codelivery of drugs/genes and dual-modality imaging in cancer treatment. Keywords: doxorubicin, codelivery, dual-modality imaging, synergistic antitumor effects, VEGF shRNA

Tony Lin,1,2,* Richard Filek,3,* Joy M Wang,4 Chong H Wu,4 Hong Liu,2 Cindy ML Hutnik1–3 1Department of Ophthalmology, Western University, 2Ivey Eye Institute, St Joseph’s Health Care, St Joseph’s Hospital, 3Department of Pathology and Laboratory Medicine, 4Department of Biology, Western University, London, ON, Canada *These authors contributed equally to this work Purpose: Impression cytology in combination with a cell autophagy marker was used to demonstrate the utility of a novel frozen section technique, to assess the health of the ocular surface, as well as to correlate autophagic cell death with the commonly used clinical tests for dry eye. Methods: Female patients over the age of 18 years who attended an outpatient ophthalmology clinic were invited to participate. Schirmer’s test, tear film break-up time and the ocular surface disease index questionnaire were used as objective and subjective clinical tests for dry eye. The cellular biomarker microtubule-associated protein light chain 3 (LC3) was used as a marker of autophagic cell death. Results: Low LC3 nuclear staining was positively correlated with Schirmer’s test

Nidhi Gupta, Catherine H Wu, George Y Wu Department of Medicine, Division of Gastroenterology–Hepatology, University of Connecticut Health Center, Farmington, CT, USA Background: Mitochondrial defects in hepatocytes can result in liver dysfunction and death. Hepatocytes have cell-surface asialoglycoprotein receptors (AsGRs) which internalize AsGs within endosomes. The aim of this study was to determine whether mitochondria could be targeted to hepatocytes by AsGR-mediated endocytosis. Materials and methods: An AsG, AsOR, was linked to polylysine to create a conjugate, AsOR-PL, and complexed with healthy and functional mitochondria (defined by normal morphology, cytochrome c assays, and oxygen-consumption rates). Huh7 (AsGR+) and SK Hep1 (AsGR–) cells were treated with a mitochondrial toxin to form Huh7-Mito– and SK Hep1-Mito– cells, lacking detectable mitochondrial DNA. An endosomolytic peptide, LLO, was coupled to AsOR to form AsOR-LLO. A lysosomal inhibitor, amantadine, was used in mitochondria-uptake studies as a control for nonspecific endosomal release. Results: Coincubation of complexed mitochondria and AsOR-LLO with Huh7-Mito– cells increased mitochondrial DNA to >9,700-fold over control at 7 days (P90% of control by 10 days. Conclusion: Rescue of mitochondria-damaged hepatocytes can be achieved by targeted uptake of normal mitochondria through receptor-mediated endocytosis. Keywords: mitochondrial toxicity, mitochondria–protein complex, receptor-mediated uptake, endosomal escape, targeted delivery

Ding-Siang Huang,1,* Hsuan-Yuan Lin,1,2,* Guey-Jen Lee-Chen,1 Hsiu-Mei Hsieh-Li,1 Chung-Hsin Wu,1 Jung-Yaw Lin1,21Department of Life Science, National Taiwan Normal University, 2Institute of Biochemistry and Molecular Biology, National Taiwan University, Taipei City, Taiwan, Republic of China*These authors contributed equally to this workAbstract: Spinocerebellar ataxia type 17 (SCA 17) is a polyglutamine disease caused by the expansion of CAG/CAA repeats in the TATA box-binding protein (TBP) gene. The Ginkgo biloba extract, EGb 761, contains flavonoids and terpenoids with a potential use for the treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. The neuroprotective effects of EGb 761 are obvious, but whether the EGb 761 has therapeutic effects in SCA 17 is still unclear. To manage our issues, we have generated TBP/79Q-expressing SH-SY5Y cells and SCA 17 transgenic mice with the mutant hTBP gene. In in vitro experiment, we observed that the EGb 761 treatment decreased the amount of sodium dodecyl sulfate-insoluble proteins in the TBP/79Q-expressing SH-SY5Y cells. We further found that the EGb 761 treatment could inhibit excitotoxicity and calcium influx and reduce the expression of apoptotic markers in glutamate-treated SH-SY5Y neuroblastoma cells. In in vivo experiment, we observed that the EGb 761 treatment (100 mg/kg intraperitoneal injection per day) could relieve the motor deficiencies of the SCA 17 transgenic mice. Our findings provide evidence that the EGb 761 treatment can be a remedy for SCA 17 via suppressing excitotoxicity and apoptosis in SCA 17 cell and animal models. Therefore, we suggest that EGb 761 may be a potential therapeutic agent for treating SCA 17.Keywords: spinocerebellar ataxia type 17, excitotoxicity, EGb 761, polyQ diseases, apoptosis

Sheue-Er Wang,1,2 Ching-Lung Lin,1 Chih-Hsiang Hsu,1 Shuenn-Jyi Sheu,3 Chung-Hsin Wu1 1Department of Life Science, National Taiwan Normal University, Taipei, 2Department of Pathological Inspection, Saint Paul’s Hospital, Taoyuan, 3Brion Research Institute of Taiwan, Taipei, Taiwan Background: Neurodegeneration is characterized by progressive neurological deficits due to selective neuronal loss in the nervous system. Huntington’s disease (HD) is an incurable neurodegenerative disorder. Neurodegeneration in HD patients shows aging-dependent pattern. Our previous study has suggested that a herbal formula B401 may have neuroprotective effects in the brains of R6/2 mice. Objective: To clarify possible mechanisms for neurodegeneration, which improves the understanding the aging process. This study focuses on clarifying neurodegenerative mechanisms and searching potential therapeutic targets in HD patients. Methods: The oxidative stress and apoptosis were compared in the brain tissue between R6/2 HD mice with and without oral B401 treatment. Expressions of proteins for oxidative stress and apoptosis in the brain tissue of R6/2 HD mice were examined by using immunostaining and Western blotting techniques. Results: R6/2 HD mice with oral B401 treatment significantly reduced reactive oxygen species levels in the blood, but markedly increased expressions of superoxide dismutase 2 in the brain tissue. Furthermore, R6/2 HD mice with oral B401 treatment significantly increased expressions of B-cell lymphoma 2 (Bcl-2), but significantly reduced expressions of Bcl-2-associated X protein (Bax), calpain, and caspase-3 in the brain tissue. Conclusion: Our findings provide evidence that the herbal formula B401 can remedy for aging-dependent neurodegeneration of R6/2 mice via suppressing oxidative stress and apoptosis in the brain. We suggest that the herbal formula B401 can be developed as a potential health supplement for ameliorating aging-dependent neurodegeneration. Keywords: neuroprotection, reactive oxygen species, superoxide dismutase 2, B-cell lymphoma 2, Bcl-2-associated X protein, calpain, caspase-3, transgenic mouse model, Huntington’s disease

Ching-Lung Lin,1 Sheue-Er Wang,2 Chih-Hsiang Hsu,1 Shuenn-Jyi Sheu,3 Chung-Hsin Wu1 1Department of Life Science, National Taiwan Normal University, Taipei, 2Department of Pathological Inspection, Soeurs de Saint Paul de Chartres Medical Corporate Body, Taoyuan City, 3Brion Research Institute of Taiwan, New Taipei City, Taiwan Abstract: Cardiac failure is often observed in aging patients with Huntington’s disease (HD). However, conventional pharmacological treatments for cardiac failure in HD patients have rarely been studied. Chinese herbal medicines, especially combined herbal formulas, have been widely used to treat cardiac dysfunctions over the centuries. Thus, we assess whether oral treatment with herbal formula B307 can alleviate cardiac failure in transgenic mice with HD. After oral B307 or vehicle treatment for 2 weeks, cardiac function and cardiomyocytes in 12-week-old male R6/2 HD mice and their wild-type littermate controls (WT) were examined and then compared via echocardiography, immunohistochemistry, and Western blotting. We found that cardiac performance in aging R6/2 HD mice had significantly deteriorated in comparison with their WT (P

Chih-Hsiang Hsu,1 Ching-Lung Lin,1 Sheue-Er Wang,1 Shuenn-Jyi Sheu,2 Chiang-Ting Chien,1 Chung-Hsin Wu1 1Department of Life Science, National Taiwan Normal University, 2Brion Research Institute of Taiwan, Taipei, Taiwan Abstract: The present study aims to elucidate the roles of nitric oxide synthase activity, oxidative stress, inflammation, and apoptosis in penile toxicity of aging mice associated with excess manganese (Mn) treatment and to investigate the effect of oral treatment with the herbal formula B401 in this respect. ICR strain mice were divided into two groups: the vehicle (sham group) and the B401 (50 mg/kg) group. The mice were orally treated for 5 days; then a high single dose of MnCl2 (100 mg/kg) was given by intraperitoneal injection to the mice. One day after MnCl2 treatment, corpora cavernosal tissues of both Mn-treated mice and their controls were simultaneously sampled to examine their immunohistochemical staining and Western blot analysis. Nitric oxide (NO) production, levels of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS), expression levels of factors governing angiogenesis (vascular endothelial growth factor), oxidative stress (catalase, superoxide dismutase 2,4-hydroxynonenal), inflammation (tumor necrosis factor alpha), apoptosis (B-cell lymphoma 2 [Bcl-2], Bcl-2-associated X protein [Bax], cleaved poly(adenosine diphosphate-ribose) polymerase [c-PARP], cytochrome C, caspase-12, and caspase-3) were evaluated in penile corpus cavernosum of the mice. We found that penile toxicity in the mice was enhanced under excess Mn treatment through reduction of NOS activity and increase in oxidative stress, inflammation, and apoptosis in the penile cavernous tissue. Furthermore, the penile toxicity in mice with manganism was alleviated by oral B401 treatment through enhancement of both nitric oxide synthesis and angiogenesis, with simultaneous reduction of oxidative stress, inflammation, and apoptosis in penile corpus cavernosum. We suggest that the herbal formula B401 may serve as a potential dietotherapeutic supplement for penile toxicity or dysfunction in aging males. Keywords: manganism, herbal formula, oxidative stress, inflammation, apoptosis

Sheue-Er Wang,1 Ching-Lung Lin,1 Chih-Hsiang Hsu,1 Shuenn-Jyi Sheu,2 Chiang-Ting Chien,1 Chung-Hsin Wu1 1Department of Life Science, National Taiwan Normal University, 2Brion Research Institute of Taiwan, Taipei, Taiwan Abstract: Huntington’s disease (HD) is a neurodegenerative disease characterized by motor dysfunction and early death. Despite years of research, the mechanisms responsible for chronic neurodegeneration of HD remain elusive. Chinese traditional medicines might provide new insights or new therapy for HD. The Chinese herbal formula B401 is a well-known Taiwan–US patent formula and a health supplement for promoting blood circulation and enhancing brain function. This study aimed to elucidate the neuroprotective effects of the Chinese herbal formula B401 on the syndrome of HD. Then, we compared the life span and body weight of R6/2 HD mice with and without oral B401 treatment. The ameliorative effects of B401 on the symptom of HD mice were investigated through behavior tests. Expressions of proteins for neuroprotection, angiogenesis, and inflammation in the brain tissue of R6/2 HD mice were compared by using immunostaining and Western blotting techniques. Our study in vitro showed that viabilities of glutamate-treated SH-SY5Y cells were significantly increased under B401 treatment. Our results in vivo showed that duration of survival was increased, body weight loss was reduced, and motor ability was improved in R6/2 HD mice under oral B401 treatment. Subcutaneous microcirculation was enhanced in 3-month R6/2 HD mice under intraperitoneal B401 injections as observed by using moorFLPI laser Doppler imager. Atrophy of cerebrum, midbrain, and cerebellum in 3-month R6/2 HD mice under oral B401 treatment was alleviated as observed by utilizing magnetic resonance imaging. Evidence from immunostaining and Western blotting analysis showed that expressions of mutant huntingtin and tumor necrosis factor-alpha were reduced, while expressions of brain-derived neurotrophic factor and vascular endothelial growth factor were enhanced in the brain tissue of 2-month R6/2 HD mice under oral B401 treatment. We suggest that the herbal formula B401 can be developed as a medical supplement for ameliorating neurodegenerative diseases of HD via reducing mutant huntingtin aggregation and excitotoxicity, enhancing neuroprotection and angiogenesis, and alleviating inflammation in the brain. Keywords: Huntington’s disease, traditional Chinese medicine, neuroprotection, excitotoxicity, angiogenesis, inflammation, R6/2 mouse model

Pin-Jui Kung,1,* Yu-Chen Tao,1,* Ho-Chiang Hsu,1 Wan-Ling Chen,1 Te-Hsien Lin,1 Donala Janreddy,2 Ching-Fa Yao,2 Kuo-Hsuan Chang,3 Jung-Yaw Lin,1 Ming-Tsan Su,1 Chung-Hsin Wu,1 Guey-Jen Lee-Chen,1 Hsiu-Mei Hsieh-Li1 1Department of Life Science, 2Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan; 3Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan *These authors contributed equally to this work Abstract: In spinocerebellar ataxia type 17 (SCA17), the expansion of a translated CAG repeat in the TATA box binding protein (TBP) gene results in a long polyglutamine (polyQ) tract in the TBP protein, leading to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On SH-SY5Y cells with inducible SCA17 TBP/Q79-green fluorescent protein (GFP) expression to test indole and synthetic derivative NC001-8 for neuroprotection. We found that indole and NC001-8 up-regulated chaperone expression to reduce polyQ aggregation in neuronal differentiated TBP/Q79 cells. The effects on promoting neurite outgrowth and on reduction of aggregation on Purkinje cells were also confirmed with cerebellar primary and slice cultures of SCA17 transgenic mice. Our results demonstrate how indole and derivative NC001-8 reduce polyQ aggregation to support their therapeutic potentials in SCA17 treatment. Keywords: spinocerebellar ataxia type 17, TATA box binding protein, polyQ aggregation, indole and derivative, therapeutics

The East Asian summer monsoon is unique among summer monsoon systems in its complex seasonality, exhibiting distinct intraseasonal stages. Previous studies have alluded to the downstream influence of the westerlies flowing around the Tibetan Plateau as key to its existence. We explore this hypothesis using an atmospheric general circulation model that simulates the intraseasonal stages with fidelity. Without a Tibetan Plateau, East Asia exhibits only one primary convective stage typical of other monsoons. As the plateau is introduced, the distinct rainfall stages—spring, pre-mei-yu, mei-yu, and midsummer—emerge, and rainfall becomes more intense overall. This emergence coincides with a pronounced modulation of the westerlies around the plateau and extratropical northerlies penetrating northeastern China. The northerlies meridionally constrain the moist southerly flow originating from the tropics, leading to a band of lower-tropospheric convergence and humidity front that produces the rainband. The northward migration of the westerlies away from the northern edge of the plateau leads to a weakening of the extratropical northerlies, which, coupled with stronger monsoonal southerlies, leads to the northward migration of the rainband. When the peak westerlies migrate north of the plateau during the midsummer stage, the extratropical northerlies disappear, leaving only the monsoon low-level circulation that penetrates northeastern China; the rainband disappears, leaving isolated convective rainfall over northeastern China. In short, East Asian rainfall seasonality results from the interaction of two seasonally evolving circulations—the monsoonal southerlies that strengthen and extend northward, and the midlatitude northerlies that weaken and eventually disappear—as summer progresses.

We present a general simulation approach for fluid-solid interactions based on the fully Eulerian reference map technique. The approach permits the modelling of one or more finitely deformable continuum solid bodies interacting with a fluid and with each other. A key advantage of this approach is its ease of use, as the solid and fluid are discretized on the same fixed grid, which greatly simplifies the coupling between the phases. We use the method to study a number of illustrative examples involving an incompressible Navier-Stokes fluid interacting with multiple neo-Hookean solids. Our method has several useful features including the ability to model solids with sharp corners and the ability to model actuated solids. The latter permits the simulation of active media such as swimmers, which we demonstrate. The method is validated favourably in the flag-flapping geometry, for which a number of experimental, numerical and analytical studies have been performed. We extend the flapping analysis beyond the thin-flag limit, revealing an additional destabilization mechanism to induce flapping.

Understanding interactions at the interfaces of carbon with ionic liquids (ILs) is crucially beneficial for the diagnostics and performance improvement of electrochemical devices containing carbon as active materials or conductive additives in electrodes and ILs as solvents or additives in electrolytes. The interfacial interactions of three typical imidazolium-based ILs, 1-alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (AMImTFSI) ILs having ethyl (C2), butyl (C4) and octyl (C8) chains in their cations, with highly oriented pyrolytic graphite (HOPG) were studied in-situ by electrochemical scanning tunneling microscopy (EC-STM). The etching of HOPG surface and the exfoliation of graphite/graphene flakes as well as cation intercalation were observed at the HOPG/C2MImTFSI interface. The etching also takes place in C4MImTFSI at −1.5 V vs Pt but only at step edges with a much slower rate, whereas C8MIm+ cations adsorbs strongly on the HOPG surface under similar conditions with no observable etching or intercalation. The EC-STM observations can be explained by the increase in van der Waals interaction between the cations and the graphite surface with increasing length of alkyl chains.

In the version of this Article originally published, the author Baran Eren was mistakenly affiliated with the Harbin Institute of Technology, China; it has now been corrected to Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.

Bimetallic and multi-component catalysts typically exhibit composition-dependent activity and selectivity, and when optimized often outperform single-component catalysts. Here we used ambient-pressure X-ray photoelectron spectroscopy (AP-XPS) and in situ and ex situ transmission electron microscopy (TEM) to elucidate the origin of composition dependence observed in the catalytic activities of monodisperse CoPd bimetallic nanocatalysts for CO oxidation. We found that the catalysis process induced a reconstruction of the catalysts, leaving CoOx on the nanoparticle surface. The synergy between Pd and CoOx coexisting on the surface promotes the catalytic activity of the bimetallic catalysts. This synergistic effect can be optimized by tuning the Co/Pd ratios in the nanoparticle synthesis, and it reaches a maximum at compositions near Co0.24Pd0.76, which achieves complete CO conversion at the lowest temperature. Our combined AP-XPS and TEM studies provide direct observation of the surface evolution of the bimetallic nanoparticles under catalytic conditions and show how this evolution correlates with catalytic properties.

On orbital timescales, higher summer insolation is thought to strengthen the continental monsoon while weakening the maritime monsoon in the Northern hemisphere. Through simulations using the Community Earth System Model, we evaluated the relative influence of perihelion precession and high obliquity in the early Holocene during the Asian summer monsoon. The major finding was that precession dominates the atmospheric heating change over the Tibetan Plateau–Himalayas and Maritime Continent, whereas obliquity is responsible for the heating change over the equatorial Indian Ocean. Thus, precession and obliquity can play contrasting roles in driving the monsoons on orbital timescales. In late spring–early summer, interior Asian continental heating drives the South and East Asian monsoons. The broad-scale monsoonal circulation further expands zonally in July–August, corresponding to the development of summer monsoons in West Africa and the subtropical Western North Pacific (WNP) as well as a sizable increase in convection over the equatorial Indian Ocean. Tropical and oceanic heating becomes crucial in late summer. Over South Asia–Indian Ocean (50°E−110°E), the precession maximum intensifies the monsoonal Hadley cell (heating with an inland/highland origin), which is opposite to the meridional circulation change induced by high obliquity (heating with a tropical origin). The existence of the Tibetan Plateau–Himalayas intensifies the precessional impact. During the late-summer phase of the monsoon season, the effect of obliquity on tropical heating can be substantial. In addition to competing with Asian continental heating, obliquity-enhanced heating over the equatorial Indian Ocean also has a Walker-type circulation impact, resulting in suppression of precession-enhanced heating over the Maritime Continent.

The interfaces between electrode and electrolyte play a vital role in various electrochemical systems. However, the understanding of such embedded interfaces and interfacial processes is still limited partly because of the short of proper characterizations tools, especially in-situ/operando techniques. In the past decade, substantial effort has been devoted in the development of in-situ/operando techniques to investigate the solid/liquid interfaces. One successful approach is the combination of in-situ liquid cells and soft x-ray absorption spectroscopy (sXAS). In this review, we showcased several recent examples using such liquid-cell-based in-situ/operando sXAS method to study different aspects of the electrode/electrolyte interface under reaction conditions, including the adsorption and deposition of solute species on electrode surface, morphological and chemical changes of electrode surface, and potential-dependent orientations of interfacial solvent molecules. These examples demonstrated capability of such in-situ/operando sXAS techniques in providing element- and chemical-sensitive interfacial information. This in-situ/operando sXAS technique also opens the way to the investigation of various solid/liquid interfaces in other important heterogeneous reactions.

Thin films of n-type γ-Cu3V2O8 are prepared with high phase purity via reactive co-sputtering deposition. Complementary X-ray spectroscopic methods are used to reveal that the valence band maximum consists of O 2p states, while the conduction band minimum is primarily composed of Cu 3d states. Therefore, γ-Cu3V2O8 is classified as a charge transfer insulator, in which the 1.80 eV indirect band gap corresponds to the O 2p → Cu 3d transition. Through photoelectrochemical measurements, the surface of γ-Cu3V2O8 photoanodes is found to display intrinsic activity for catalyzing water oxidation that is stable with time. The combination of a small optical band gap, suitable valence band energy, and excellent photoelectrochemical stability suggests that γ-Cu3V2O8 could be a promising photoanode material. However, it is found that the charge extraction efficiency from these semiconductor photoanodes is strongly limited by a short (20-40 nm) hole diffusion length. Characterization of the electronic structure and transport properties of γ-Cu3V2O8 photoanodes suggests strategies for improving energy conversion efficiency and provides fundamental insights that can be used for understanding and evaluating function in a broader class of emerging ternary metal oxides.

Ambient-pressure X-ray photoelectron spectroscopy (XPS) was used to investigate the reactions of CO, H2, and their mixtures on Co foils. We found that CO adsorbs molecularly on the clean Co surface and desorbs intact in vacuum with increasing rate until ∼90°C where all CO desorbs in seconds. In equilibrium with 100 mTorr gas, CO dissociates above 120°C, leaving carbide species on the surface but no oxides, because CO efficiently reduces the oxides at temperatures ∼100°C lower than H2. Water as impurities or produced by reaction of CO and H2 efficiently oxidizes Co even at room temperature. Under 97:3 CO/H2 mixture and with increasing temperatures, the Co surface becomes more oxidized and covered by hydroxyl groups until ∼150°C where surface starts to get reduced, accompanied by carbide accumulation indicative of CO dissociation. A similar trend was observed for 9:1 and 1:1 mixtures, but surface reduction begins at higher temperatures. (Figure Presented).

The early Holocene climatic optimum is associated with perihelion precession and high obliquity, though most studies emphasize the former over the latter. Asian monsoon proxy records only decisively show the precessional impact. To explore the obliquity effect, four climate simulations are conducted by fixing orbital parameters of present-day (0K), early Holocene (11K), the lowest obliquity (31K), and 11K's precession and eccentricity with 31K's obliquity (11Kp31Ko). We show that high obliquity significantly augments the precessional impact by shifting the Asian monsoon farther north than present. By contrast, the present-day monsoon seasonality can still be identified in the simulations with low obliquity. We argue that the upper tropospheric (South Asian) and lower tropospheric (North Pacific) high-pressure systems are affected by the subtropical atmospheric heating changes responding to obliquity. As a consequence, associated with the changes in meridional gradients of geopotential height and temperature made by the heating, midlatitude transient eddies and monsoon-midlatitude interactions are modulated.

Orbital forcing exerts a strong influence on global monsoon systems, with higher summer insolation leading to stronger summer monsoons in the Northern Hemisphere. However, the associated regional and seasonal changes, particularly the interaction between regional monsoon systems, remain unclear. Simulations using the Community Earth System Model demonstrate that the western North Pacific (WNP) summer monsoon responds to orbital forcing opposite to that of other major Northern Hemisphere monsoon systems. Compared with its current climate state, the simulated WNP monsoon and associated lower-tropospheric trough is absent in the early Holocene when the precession-modulated Northern Hemisphere summer insolation is higher, whereas the summer monsoons in South and East Asia are stronger and shift farther northward. We attribute the weaker WNP monsoon to the stronger diabatic heating of the summer Asian monsoon—in particular over the southern Tibetan Plateau and Maritime Continent—that in turn strengthens the North Pacific subtropical high through atmospheric teleconnections. By contrast, the impact of the midlatitude circulation changes on the WNP monsoon is weaker when the solar insolation is higher. Prior to the present WNP monsoon onset, the upper-tropospheric East Asian jet stream weakens and shifts northward; the monsoon onset is highly affected by the jet-induced high potential vorticity intrusion. In the instance of the extreme perihelion-summer, the WNP monsoon is suppressed despite a stronger midlatitude precursor than present-day, and the midlatitude circulation response to the enhanced South Asian precipitation is considerable. These conditions indicate internal monsoon interactions of an orbital scale, implying a potential mechanistic control of the WNP monsoon.

The summer rainfall climate of East Asia underwent large and abrupt changes during past climates, in response to precessional forcing, glacial-interglacial cycles as well as abrupt changes to the North Atlantic during the Last Glacial. However, current interpretations of said changes are typically formulated in terms of modulation of summer monsoon intensity, and do not account for the known complexity in the seasonal evolution of East Asian rainfall, which exhibits sharp transition from the Spring regime to the Meiyu, and then again from the Meiyu to the Summer regime. We explore the interpretation that East Asian rainfall climate undergoes a modulation of its seasonality during said paleoclimate changes. Following previous suggestions we focus on role of the westerly jet over Asia, namely that its latitude relative to Tibet is critical in determining the stepwise transitions in East Asian rainfall seasons. In support of this linkage, we show from observational data that the interannual co-variation of June (July-August) rainfall and upper tropospheric zonal winds show properties consistent with an altered timing of the transition to the Meiyu (Summer), and with more northward-shifted westerlies for earlier transitions.We similarly suggest that East Asian paleoclimate changes resulted from an altered timing in the northward evolution of the jet and hence the seasonal transitions, in particular the transition of the jet from south of the Plateau to the north that determines the seasonal transition from Spring rains to the Meiyu. In an extreme scenario - which we speculate the climate system tended towards during stadial (cold) phases of D/O stadials and periods of low Northern Hemisphere summer insolation - the jet does not jump north of the Plateau, essentially keeping East Asia in prolonged Spring conditions.We argue that this hypothesis provides a viable explanation for a key paleoproxy signature of D/O stadials over East Asia, namely the heavier mean δ18O of precipitation as recorded in speleothem records. The southward jet position prevents the low-level monsoonal flow - which is isotopically light - from penetrating into the interior of East Asia; as such, precipitation there will be heavier, consistent with speleothem records. This hypothesis can also explain other key evidences of East Asian paleoclimate changes, in particular the occurrence of dusty conditions during North Atlantic stadials, and the southward migration of the Holocene optimal rainfall.

We develop computational methods for the simulation of osmotic swelling phenomena relevant to microscopic vesicles containing transformable solute molecules. We introduce stochastic immersed boundary methods (SIBMs) that can capture osmotically driven fluid transport through semipermeable elastic membranes subject to thermal fluctuations. We also develop numerical methods to handle within SIBMs an elastic shell model for a neo-Hookean material. Our extended SIBM allows for capturing osmotic swelling phenomena driven by concentration changes and interactions between a discrete collection of confined particles while accounting for the thermal fluctuations of the semipermeable membrane and the hydrodynamic transport of solvent. We use our computational methods to investigate osmotic phenomena in regimes that go beyond the classical Van't Hoff theory. We develop statistical mechanics theories for osmotic swelling of vesicles when there are significant interactions between particles that can transform over time. We validate our theoretical results against detailed computational simulations. Our methods are expected to be useful for a wide class of applications allowing for the simulation of osmotically driven flows, thermally fluctuating semipermeable elastic structures, and solute interactions.

Lithium-sulfur batteries have a theoretical specific energy that is a factor of five greater than that of current lithium-ion batteries, but suffer from consequences of the solubility of lithium polysulfide reaction intermediates that form as the batteries are charged and discharged. These species can react with each other and diffuse out of the cathode, causing battery capacity to fade and ultimately, cell failure. In spite of work that has spanned four decades, fingerprints of polysulfides have not yet been established, precluding a systematic study of lithium-sulfur chemistry. Herein we demonstrate the use of principal component analysis of X-ray absorption spectroscopy (XAS) to obtain fingerprints of lithium polysulfides. This approach enables interpretation of spectral data without any assumptions regarding the origin of the observed spectral features or knowledge of the stability of the polysulfide species of interest.We show that in poly(ethylene oxide)-based solid electrolytes containing polysulfides made by chemically reacting Li2S and elemental sulfur, Li2S2 and Li2S6 spontaneously disproportionate to give binary Li2S/Li2S4 and Li2S4/Li 2S8 mixtures, respectively, while Li2S 4 and Li2S8 exist as single molecular species. XAS fingerprints of Li2S4 and Li2S8 are thus presented. © 2014 The Electrochemical Society.

In nature, animals must contend with the presence of noise, which may limit their ability to detect prey, attract mates and escape predators. Sources of noise vary and may originate from natural (e.g. animal sounds, water) or anthropogenic (e.g. traffic, construction) sources. The vibratory sensory modality has long been overlooked in the study of anthropogenic effects on wildlife. Human-induced environmental changes may introduce noise sources as well as artificial substrates that alter vibratory noise profiles, leading to maladaptive behavioural responses. We conducted field measurements of vibratory noise on various substrate types (natural and artificial) used by animals in human-developed habitats. Next, we conducted laboratory experiments on how vibratory noise affects the prey detection ability of the European garden spider, Araneus diadematus. We tested whether changes in vibratory noise profiles consistent with anthropogenic alterations of vibratory habitats are sufficient to alter the spider's sensitivity to prey cues. We found that overall noise amplitude on artificial substrates was lower and less variable across contexts compared with natural substrates. In experiments with different noise levels, we observed that garden spiders showed noise-dependent changes in sensitivity to prey-mimicking cues, with response thresholds lowest at intermediate noise levels. Experimental levels of intermediate noise consistent with field measurements on natural substrates suggest that spiders' predatory performance is higher when webs are constructed on natural substrates. This suggests that human-introduced substrates may interfere with spiders' predatory performance. As human activities and habitat alteration are widespread, our findings highlight the need to consider the vibratory sensory channel in assessing anthropogenic impacts on wildlife. © 2014 The Association for the Study of Animal Behaviour.

The increasing volume of scientific publications has created a need for more efficient and effective literature review processes. Bibliometric analysis is a quantitative approach to analysing bibliographic data extracted from research studies to identify publishing patterns and trends within specific knowledge domains. Science mapping is a widespread technique in bibliometric analysis that enables researchers to reveal the structure of their respective fields and identify dominant themes. However, there is still a lack of clarity and transparency in describing the science mapping process, which can hinder continued refinement and improvement of this critical field of research. This study provides a comprehensive overview of science mapping in bibliometric analysis based on published review studies from prestigious international journals. It outlines the science mapping mechanism and explores challenges and opportunities, focusing on incorporating text mining approaches to support the analytical literature review process. The study sheds light on previously unexplored mechanisms in the literature of bibliometric analysis, revealing gaps in existing research. The study contributes to the growing body of research on bibliometric analysis by highlighting the need for continuous improvement and the deployment of text mining techniques to support the analysis of scientific publication data. This study offers valuable insights for researchers, policymakers, and practitioners seeking to enhance their understanding of science mapping and bibliometric analysis. [ABSTRACT FROM AUTHOR]

The poor high‐temperature oxidation properties of Ti‐6Al‐4 V (titanium‐aluminum‐vanadium) alloy limit its applications under high‐temperature components of aero‐engines. In this study, the aluminum‐silicon coatings with different silicon content were fabricated on titanium‐aluminum‐vanadium alloy via the hot dipping route. A metallurgical bond was established at the interface between aluminum‐silicon coatings and substrates following the hot dipping. The results showed that three different coatings were formed: titanium(aluminum, silicon)3+ liquid‐(aluminum, silicon), titanium(aluminum, silicon)3+ τ2+ liquid‐(aluminum, silicon) and τ1+ τ2+ liquid‐(aluminum, silicon). Furthermore, the formation of aluminum‐silicon coatings was analyzed by diffusion path theory. The coated alloy was subjected to a high‐temperature oxidation test at 850 °C, and the weight gains were only 5.1 % to 22.4 % of the bare alloy. The coatings improved the high‐temperature oxidation resistance of titanium‐aluminum‐vanadium alloy. The most favorable oxidation behavior was noticed for the titanium(aluminum, silicon)3+liquid‐(aluminum, silicon) coatings. The higher the silicon content in titanium(aluminum, silicon)3+liquid‐(aluminum, silicon) coatings, the more excellent high‐temperature oxidation resistance was achieved. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of a disintegrin and metalloprotease domain 10 (ADAM10) inhibitor on synaptic structure and blood-brain barrier (BBB) permeability in rats with autism-like behavior. Methods A total of 50 male offspring rats with prenatal exposure to valproic acid (VPA) to induce autism-like behavior were randomly divided into VPA group and ADAM10 inhibitor, TAT-Pro-ADAM10 (709-729) group (TAT-Pro group), with 25 rats in each group. And another 25 offspring male rats induced by normal saline during pregnancy served as control group (CON group). The TAT-Pro group was given intraperitoneal injection on postnatal day 20 with 3 nmol/g TAT-Pro-ADAM10 (709-729), and equal volumes of normal saline were given to the CON and VPA groups. The changes of body mass and tail length of offspring rats were measured and recorded during modeling. Western blotting was performed to detect the protein levels of ADAM10, vascular endothelial cadherin (VE-Cad), Occludin, zonula occludens-1 (ZO-1), post-synaptic density protein-95 (PSD95), and synaptophysin (SYN) in the hippocampal tissue of the offspring rats in 24 h after administration. The expression of ZO-1 protein was further verified by immunofluorescence assay. Behavioral tests were conducted from postnatal day 24, including open field, grooming, three-chamber social interaction, and water maze tests. The density of dendritic spines in hippocampal tissue in the offspring rats on postnatal day 28 was detected by Golgi staining. Results Compared with the VPA group, the TAT-Pro group showed no significant changes in body weight and tail length, but significantly improved repetitive stereotyped behaviors, social skills and learning memory ability (P < 0.05), reduced protein levels of ADAM10 and PSD95 in hippocampal tissues (P < 0.05), and elevated levels of VE-cad and Occludin (P < 0.05). The density of dendritic spines was significantly reduced (P < 0.05), and the number of immature dendritic spines also decreased in the TAT-Pro group than the VPA group. Conclusion Inhibition of ADAM10 overexpression during the critical period of synaptic development can alleviate learning and memory dysfunctions in VPA-induced rats with autism-like behavior, and has a certain restorative effect on abnormal synaptic structures and blood-brain barrier permeability.

In this study, high internal phase Pickering emulsions (HIPPEs) were prepared using soybean isolate protein microgel particles, which were prepared by gel disruption, as a stabilizer. Confocal laser scanning microscopy (CLSM) showed that the oil droplets were encapsulated within protein particles, and some of them were observed to exhibit a polyhedral morphology due to stacking, which is a typical feature of typical O/W-type HIPPEs. Increasing oil content and protein particle concentration improved the viscosity, storage modulus and gel strength of the system, which endowed the emulsion with 3D printing ability. When the oil content was 75% and the protein particle concentration was 3.0%, the accuracy and stability of the printed model were 93.35% and 98.72%, respectively. The results of this study indicated that HIPPEs can be used as an effective ink for 3D printing of food products, which provide a theoretical basis for expanding the application of 3D printing in the food field.

ObjectiveTo analyze the epidemiological characteristics, spatiotemporal clustering, and changing trends of hand, foot, and mouth disease (HFMD) in Fujian province from 2009 to 2022. MethodsData on HFMD cases in Fujian province from 2009 to 2022 were obtained from the Surveillance Reporting Management System of the China Information System for Disease Control and Prevention. Descriptive epidemiology, Joinpoint regression, spatial autocorrelation analysis, and spatiotemporal scanning were used to analyze HFMD in Fujian province. ResultsA total of 927 366 HFMD cases were reported in Fujian province from 2009 to 2022, with an average annual reported incidence rate of 172.15/100 000, severe case rate of 0.62/100 000, mortality rate of 0.018/100 000, and case fatality rate of 10.68/100 000. The reported incidence rate, severe case rate, mortality rate, and case fatality rate of HFMD all showed a trend of first increasing and then decreasing. HFMD incidence exhibited obvious seasonality, with two peaks each year, the main peak in May – June and the secondary peak in September – November. The key population was children aged < 5 years, accounting for 91.33% of all cases. Among 40 637 laboratory-confirmed cases, accounting for 4.38% of all confirmed cases, 28.93% (11 756/40 637) were positive for enterovirus A71 (EV-A71), 20.38% (8 280/40 637) were positive for coxsackievirus A16 (COX-A16), and 50.69% (20 601/40 637) were positive for other enteroviruses. Spatiotemporal clustering of HFMD existed in Fujian province (Moran′s I = 0.15 – 0.56, P < 0.05). Spatiotemporal scanning detected three clusters, one primary cluster and two secondary clusters. ConclusionObvious spatiotemporal clustering of HFMD existed in Fujian province from 2009 to 2022, and the overall epidemic trend first increased and then decreased. Prevention and control of the epidemic should focus on the prefecture-level city unit and strengthen HFMD prevention and control for key populations and before the arrival of epidemic peaks.

Accurate and complete road network extraction plays a critical role in urban planning, street navigation, and emergency response. At present, narrow roads are a main feature in most public road datasets. However, the continuity and boundary completeness of the extraction results for these narrow roads are relatively poor, due to their varied shapes, uneven spatial distribution, and the presence of various interfering elements. To address these issues, this study introduces a novel network, the Self-weighted Global Context Road Extraction Network (SWGE-Net), which integrates a dilate block and an improved coordinate attention mechanism to effectively capture the complex details and spatial information of narrow roads. Furthermore, most public road training datasets often lack labels for very narrow roads, this omission leads to poor extraction results for these roads in test datasets. In order to further improve the extraction capability for unlabeled, extremely narrow roads, this study introduces another network called the Multi-scale Information Fusion Road Extraction Network (MSIF-Net), which uses the same encoders as SWGE-Net and has a special module for merging information at different scales. This module, with a dilate block and pyramid pooling-based decoder, makes the network better at recognizing and combining features of different sizes. Experimental results indicate that SWGE-Net outperforms the baseline network with road IoU scores of 71.57% and 60.67% on the DeepGlobe and CHN6-CUG road datasets, respectively an improvement of 18.51% and 5.40%. Meanwhile, MSIF-Net not only exceeds the baseline in road IoU scores for both datasets, but also achieves the best performance in extracting unlabeled, extremely narrow roads in qualitative experiments.

With the gradual increase of the proportion of renewable energy in the power system, the risk of frequency fluctuation in the power system increases. Flywheel and lithium battery can complement each other as hybrid energy storage applied in the primary frequency regulation of the grid, effectively solving the problem of system frequency fluctuation. In order to give full play to the respective frequency regulation advantages of flywheel and lithium battery, a primary frequency regulation (PFR) strategy for battery-flywheel hybrid energy storage based on adaptive state of charge (SOC) is proposed. Firstly, a weight allocation PFR is proposed, containing three control methods, namely, positive and negative virtual inertia control and virtual droop control. Secondly, the parameters of the PFR are corrected by using the SOC of the doubly-fed flywheel and the Li-ion battery, so as to improve the PFR capability of hybrid energy storage near the threshold of SOC. Finally, the control strategy of the hybrid energy storage with the other control strategies is compared with that of this paper in simulation under the frequency regulation scenarios. The results show that the SOC fluctuation range of the energy storage system of the strategy proposed in this paper is minimum. The battery will not be overcharged and overdischarged, and the system frequency fluctuation is kept no more than ±0.2 Hz, which proves that the proposed strategy can improve the frequency stability of the grid.

Abstract Intelligent nursing wheelchairs significantly enhance mobility and independence for elderly individuals with disabilities. However, traditional designs often suffer from large turning radii that restrict their functionality in confined spaces. Addressing this critical challenge, this study introduces an innovative design utilizing a Mecanum wheel chassis that allows for omnidirectional movement, significantly improving maneuverability and stability. Our design incorporates independently controlled Mecanum wheels, overcoming traditional constraints and enhancing user autonomy. To address issues such as wheel spacing variations and hub center tilting, which can lead to slipping and inaccurate motion control, we developed a novel suspension system that stabilizes the chassis, minimizes slipping risks, and boosts motion control accuracy. Experimental validations, including shock absorption and positioning tests, demonstrate that our suspension system markedly enhances the wheelchair's control performance and stability, thereby providing users with enhanced precision and potentially improving their quality of life.