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This study investigated the relative effectiveness of a mix-and-match vaccination strategy, primarily comprising ChAdOx1 nCOV-19, mRNA-1273, BNT162b2, and a protein-based vaccine, MVC-COV1901, against COVID-19 in a healthcare worker (HCW) cohort in Taiwan during a period when the Omicron variant was predominant. The analysis included a total of 21,729 HCWs and recorded 3,672 infections with no severe disease nor death. Two main findings were observed from the study. Firstly, for those with ChAdOx1 nCOV-19 as primary series, a booster dose with BNT162b2 was associated with a small decrease in the risk of acquiring infection compared to those with mRNA-1273 as a booster (Adjust hazard ratio [Adj HR] 0.864; 95% confidence interval [CI] 0.761‒0.981, P = .024). Secondly, for HCWs receiving an mRNA-1273 booster, compared to those receiving ChAdOx1 nCOV-19 as the primary series, mixed primary series and homologous mRNA-1273 primary series were associated with a higher (Adj HR 1.144; 95% CI 1.021‒1.282, P = .021) and lower risk (Adj HR 0.735; 95% CI 0.671‒0.805, P

Background: Mycoplasma pneumoniae is a major pathogen for community-acquired pneumonia and frequently causes outbreaks in children. M. pneumoniae-specific antibody response is detected upon acute infection and the serology is widely used in the clinical setting. Nevertheless, the cellular basis for antigen-specific antibody response to acute M. pneumoniae infection is largely undetermined in children. Methods: Hospitalized children with community-acquired pneumonia were enrolled and the infection with M. pneumoniae was confirmed with positive PCR result and negative findings for other pathogens. The M. pneumoniae P1-specific antibody-secreting B cell (ASC) response was examined with the ex vivo enzyme-linked immunosorbent spot assay and the relationships between the ASC frequency and serological level and clinical parameters within M. pneumoniae patients were studied. Results: A robust M. pneumoniae P1-specific ASC response was detected in the peripheral blood among M. pneumoniae-positive patients. By contrast, no M. pneumoniae-specific ASCs were detected among M. pneumoniae-negative patients. The IgM-secreting B cells are the predominant class and account for over 60% of total circulating M. pneumoniae-specific ASCs in the acute phase of illness. The M. pneumoniae P1-specific ASC frequency significantly correlated with the fever duration, and the IgG ASC frequency significantly correlated with serological titer among patients. Conclusion: A rapid and potent elicitation of peripheral M. pneumoniae-specific ASC response to acute infection provides the cellular basis of antigen-specific humoral response and indicates the potential of cell-based diagnostic tool for acute M. pneumoniae infection. Our findings warrant further investigations into functional and molecular aspects of antibody immunity to M. pneumoniae.

Background/purpose: Superspreading events (SSEs) are pivotal in the spread of SARS-CoV-2. This study aimed to investigate an SSE of COVID-19 in a hospital and explore the transmission dynamics and heterogeneity of SSE. Methods: We performed contact tracing for all close contacts in a cluster. We did nasopharyngeal or throat swabbing for SARS-CoV-2 by real-time RT-PCR. Environmental survey was performed. The epidemiological and clinical characteristics of the SSE were studied. Results: Patient 1 with congestive heart failure and cellulitis, who had onset of COVID-19 two weeks after hospitalization, was the index case. Patient 1 led to 8 confirmed cases, including four health care workers (HCW). Persons tested positive for SARS-CoV-2 were HCW (n = 4), patient 1's family (n = 2), an accompanying person of an un-infected in-patient (n = 1), and an in-patient admitted before the SSE (n = 1). The attack rate among the HCW was 3.2 % (4/127). Environmental survey confirmed contamination at the bed rails, mattresses, and sink in the room patient 1 stayed, suggesting fomite transmission. The index case's sputum remained positive on illness day 35. Except one asymptomatic patient, at least three patients acquired the infection from the index case at the pre-symptomatic period. The effective reproduction number (Rt) was 0.9 (8/9). Conclusion: The host factor (heart failure, longer viral shedding), transmissibility of SARS-CoV-2 (Rt, pre-symptomatic transmission), and possible multiple modes of transmission altogether contributed to the SSE. Rapid response and advance deployment of multi-level protection in hospitals could mitigate COVID-19 transmission to one generation, thereby reducing its impact on the healthcare system.

Background/purpose: Morbidity and mortality from typhoid and paratyphoid fever remain an important problem for public health authorities in developing countries. In countries with lower incidences, most cases occur in travelers who visit regions in which typhoid and paratyphoid fever are highly endemic. The aim was to evaluate the source and transmission dynamics of typhoid and paratyphoid fever in Taiwan by using genomic analysis. Methods: During 2012–2019, 15 clinical isolates of Salmonella Typhi and S. Paratyphi A were collected. Demographic and clinical information of the infections were analyzed. We performed whole genome sequencing and evolutionary analysis on these isolates. Results: Clinical and microbiological data from 7 S. Typhi and 8 S. Paratyphi A isolates in Taiwan showed epidemiological and bacterial genomic link to the infection in South and Southeast Asia. The Taiwanese typhoidal isolates also share highly similar genomes with those collected from UK, indicating global circulation of the typhoidal clones. Local transmission of the imported but indigenized international clones was observed. Mutations occurring at gyrA 83 aa, including S83Y and S83F, were identified in the ciprofloxacin-resistant strains. Conclusion: Due to the advance of global transportation and communication, the transmission mode of infectious disease has been modified. Domestic typhoid and paratyphoid fever caused by international resistant clones can occur in low-incidence countries. Genome analysis showed that the indigenous clone originally imported from other countries has been circulating in Taiwan for over a decade.

Although in a critical position in the economy, the paper industry releases a lot of wastewater that requires adequate treatment for sustainable development. This study presents an application of Life cycle assessment (LCA) with the ReCiPe tool on the wastewater treatment plant (WWTP) of a paper factory in Vietnam to evaluate the environmental effect of the individual techniques in WWTP, especially the internal circulation (IC) reactor, a pioneer and practical anaerobic technology. Both Midpoint and Endpoint categories results demonstrated that chemical use and electricity consumption mainly contributed to the environmental impact in the WWTP. The Dissolved air flotation (DAF) and Moving bed biofilm reactor (MBBR) are classified as effective techniques to reduce the impacts on the environment. Moreover, the comparison of LCA between IC and up-flow anaerobic sludge bed (UASB) shows that IC is the better practically green technique for the environment. HIGHLIGHTS Life cycle assessment was applied in a paper mill wastewater treatment plant.; Midpoint and Endpoint indicators were employed to evaluate environmental impact.; Two scenarios of electricity generating from biogas between Internal circulation and up-flow anaerobic sludge bed were investigated.; Chemicals use and energy consumption were determined to be the most factors to damage indicators.;

Visual feedback that reinforces accurate movements may motivate skill acquisition by promoting self-confidence. This study investigated neuromuscular adaptations to visuomotor training with visual feedback with virtual error reduction. Twenty-eight young adults (24.6 ± 1.6 years) were assigned to error reduction (ER) (n = 14) and control (n = 14) groups to train on a bi-rhythmic force task. The ER group received visual feedback and the displayed errors were 50% of the real errors in size. The control group was trained with visual feedback with no reduction in errors. Training-related differences in task accuracy, force behaviors, and motor unit discharge were contrasted between the two groups. The tracking error of the control group progressively declined, whereas the tracking error of the ER group was not evidently reduced in the practice sessions. In the post-test, only the control group exhibited significant task improvements with smaller error size (p = .015) and force enhancement at the target frequencies (p = .001). The motor unit discharge of the control group was training-modulated, as indicated by a reduction of the mean inter-spike interval (p = .018) and smaller low-frequency discharge fluctuations (p = .017) with enhanced firing at the target frequencies of the force task (p = .002). In contrast, the ER group showed no training-related modulation of motor unit behaviors. In conclusion, for young adults, ER feedback does not induce neuromuscular adaptations to the trained visuomotor task, which is conceptually attributable to intrinsic error dead-zones.

Abstract Background Error amplification (EA), virtually magnify task errors in visual feedback, is a potential neurocognitive approach to facilitate motor performance. With regional activities and inter-regional connectivity of electroencephalography (EEG), this study investigated underlying cortical mechanisms associated with improvement of postural balance using EA. Methods Eighteen healthy young participants maintained postural stability on a stabilometer, guided by two visual feedbacks (error amplification (EA) vs. real error (RE)), while stabilometer plate movement and scalp EEG were recorded. Plate dynamics, including root mean square (RMS), sample entropy (SampEn), and mean frequency (MF) were used to characterize behavioral strategies. Regional cortical activity and inter-regional connectivity of EEG sub-bands were characterized to infer neural control with relative power and phase-lag index (PLI), respectively. Results In contrast to RE, EA magnified the errors in the visual feedback to twice its size during stabilometer stance. The results showed that EA led to smaller RMS of postural fluctuations with greater SampEn and MF than RE did. Compared with RE, EA altered cortical organizations with greater regional powers in the mid-frontal cluster (theta, 4–7 Hz), occipital cluster (alpha, 8–12 Hz), and left temporal cluster (beta, 13–35 Hz). In terms of the phase-lag index of EEG between electrode pairs, EA significantly reduced long-range prefrontal-parietal and prefrontal-occipital connectivity of the alpha/beta bands, and the right tempo-parietal connectivity of the theta/alpha bands. Alternatively, EA augmented the fronto-centro-parietal connectivity of the theta/alpha bands, along with the right temporo-frontal and temporo-parietal connectivity of the beta band. Conclusion EA alters postural strategies to improve stance stability on a stabilometer with visual feedback, attributable to enhanced error processing and attentional release for target localization. This study provides supporting neural correlates for the use of virtual reality with EA during balance training.

Background: Stroboscopic vision (SV), intermittent visual blocking, has recently been incorporated into postural training in rehabilitation. This study investigated interactions of postural fluctuation dynamics and cortical processing for the elderly during stabilometer stance with SV.Methods: Thirty-five healthy elderly maintained an upright stance on a stabilometer. Along with postural fluctuation dynamics, EEG relative power and EEG-EEG connectivity were used to contrast neuromechanical controls of stabilometer stance with SV and full-vision.Results: Compared with the full-vision, SV led to greater postural fluctuations with lower sample entropy and mean frequency (MF). SV also reduced regional power in the mid-frontal theta cluster, which was correlated to SV-dependent changes in the size of postural fluctuations. SV also enhanced the alpha band supra-threshold connectivity in the visual dorsal and frontal–occipital loops of the right hemisphere, and the supra-threshold connectivity from Fp2 positively related to variations in the MF of postural fluctuations.Conclusion: SV adds challenge to postural regulation on the stabilometer, with the increasing regularity of postural movements and fewer corrective attempts to achieve the postural goal. The elderly shift over-reliance on visual inputs for posture control with more non-visual awareness, considering deactivation of the dorsal visual stream and visual error processing.

Background/Purpose: Post-stroke dysphagia is a frequent complication. Although most patients with dysphagia recover after the acute phase, some patients require long-term enteral feeding, either through a nasogastric (NG) or gastrostomy tube; the effectiveness of using either tube is still under debate. This study elucidated the natural course of NG tube installation and removal and examined the predictors and associating factors based on clinical and brain imaging data. Methods: This retrospective cohort study with medical record reviews recruited patients received NG tube installation after their acute stroke events between January 1, 2016, and December 31, 2016. Inclusion criteria were subjects above 20 years of age and with a diagnosis of a newly onset stroke except SAH whose comprehensive clinical and imaging data were available. Survival analysis was performed for the right-censored data because some patients were lost to follow-up after discharge or transferal. Results: In total we recruited 135 patients. Among these patients, the timing of their NG tube removal reached a plateau at 12–16 weeks after stroke. The modified Rankin score on discharge, representing the overall subacute disease status, was the most significant factor. Other clinical variables could be divided into 2 categories: baseline patient characteristics and stroke event severity. Moreover, semi-quantitative brain imaging scores corresponding to the aforementioned 3 categories were correlated significantly. Conclusion: In Taiwan, the NG tube removal rate reached a plateau at around 12–16 weeks after stroke onset. Variables related to long-term NG tube use were divided into baseline characteristics of patient and stroke event severity.

Background: The most severe form of pneumococcal disease is invasive pneumococcal disease (IPD), including empyema, sepsis and meningitis. Thomsen-Friedenreich antigen (TA; Galβ1-3GalNAc) activation is known to be a predictor of Streptococcus pneumoniae-associated hemolytic uremic syndrome (Sp-HUS). There have been limited data to correlate TA activation and overall disease severity of IPD in children. The study aimed to prove the positive correlation between TA activation and disease severity and to demonstrate the trend of TA level during the disease course. Methods: We retrospectively reviewed the medical records from 38 pediatric patients aged from 0 to 18 years with microbiologically-confirmed IPD between 2010 and 2015 at a medical center in Taiwan. All cases underwent TA activation testing by the fluorescence-labeled peanut lectin agglutination method. Medical information including demographic data, laboratory findings, co-morbidities, and outcome was collected and reviewed. We compared the clinical manifestations and associated co-morbidities between TA-positive and TA-negative patients. Results: Among the 38 patients, 25 (66%) showed TA activation. Compared to TA-negative patients, patients with TA activation had a statistically higher rate of prolonged anemia, thrombocytopenia, and acute kidney injury. TA-positive patients also had a longer intensive care unit stay and overall hospitalization days. The TA levels usually peaked 5–10 days after disease onset. Twenty-one pneumococcal isolates were recovered from the patients and serotyping was determined in 11 isolates: 10 serotype 19A and 1 serotype 3. Conclusions: TA determination not only helps to diagnose Sp-HUS but also is a predictor for IPD severity. Among hospitalized patients with severe pneumococcal disease, the peak of TA level usually appeared 5–10 days after disease onset.

• Higher in survival ratio of snakehead in applied aquaponics to normal culture system was 99.76% and 71.40%. • Three times higher fish yield in aquaponics to normal culture system was 366 kg and 130 kg. • The productions of water spinach were more advantage in aquaponics systems: 406.4 kg vs. 188 kg. • The total income from snakehead and water spinach in applied aquaponics was 4 times higher than normal farming systems. • This study did not use any chemicals in aquaponics that produce fresh and healthy food to consumers. This study was carried out to investigate the viability of utilizing aquaponic technology in culturing local fish: snakehead Channa striata and water spinach Ipomoea aquatica. Snakehead was raised for 150 days in a floating plastic pond with an area of 3 × 4 × 1.2 m having a capacity volume of ∼14.4 m3. Fish were randomly arranged into two experimental systems at density of ∼0.3 kg fingerlings/m3 e.g. SAQ – snakehead in aquaponics; SC – snakehead in normal system where control ponds were continuously aerated with ∼20% daily exchange of water. Fish were fed commercial feed twice a day. Initial results showed that in aquaponics compared with normal systems the SAQ efficiency exhibited 70% water exchange; five times lower in NH 3 level: (0.01–0.03 mg/L vs. 0.05–0.16 mg/L); three times lower in NO 2 level: (0.28–0.58 mg/L vs. 0.56–2.59 mg/L). Snakehead production was significantly higher in aquaponics with higher survival ratio of fish: 99.76% vs. 71.40%; ∼3 times higher in fish yield: 366 kg vs. 130 kg. The production of water spinach was also elevated in aquaponics versus normal systems 406.4 kg vs. 188 kg. The total income from snakehead and water spinach in SAQ were 4 times higher than in normal farming systems: 1219.42 $US and 307.04 $US. Based on the results of the current study, it is expected that applying aquaponics utilizing local available materials and species will enhance the sustainability of the overall system and keep the aquaponics lasting and expanding to social life especially on sustainable culturing snakehead Channa striata. [ABSTRACT FROM AUTHOR]

A high salt intake exacerbates insulin resistance, evoking hypertension due to systemic perivascular inflammation, oxidative-nitrosative stress and endothelial dysfunction. Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARBs) have been shown to abolish inflammation and redox stress but only partially restore endothelial function in mesenteric vessels. We investigated whether sympatho-adrenal overactivation evokes coronary vascular dysfunction when a high salt intake is combined with insulin resistance in male Goto-Kakizaki (GK) and Wistar rats treated with two different classes of ß-blocker or vehicle, utilising synchrotron-based microangiography in vivo. Further, we examined if chronic carvedilol (CAR) treatment preserves nitric oxide (NO)-mediated coronary dilation more than metoprolol (MET). A high salt diet (6% NaCl w/w) exacerbated coronary microvessel endothelial dysfunction and NO-resistance in vehicle-treated GK rats while Wistar rats showed modest impairment. Microvascular dysfunction was associated with elevated expression of myocardial endothelin, inducible NO synthase (NOS) protein and 3-nitrotyrosine (3-NT). Both CAR and MET reduced basal coronary perfusion but restored microvessel endothelium-dependent and -independent dilation indicating a role for sympatho-adrenal overactivation in vehicle-treated rats. While MET treatment reduced myocardial nitrates, only MET treatment completely restored microvessel dilation to dobutamine (DOB) stimulation in the absence of NO and prostanoids (combined inhibition), indicating that MET restored the coronary flow reserve attributable to endothelium-derived hyperpolarisation (EDH). In conclusion, sympatho-adrenal overactivation caused by high salt intake and insulin resistance evoked coronary microvessel endothelial dysfunction and diminished NO sensitivity, which were restored by MET and CAR treatment in spite of ongoing inflammation and oxidative-nitrosative stress presumably caused by uninhibited renin-angiotensin-aldosterone system (RAAS) overactivation. [ABSTRACT FROM AUTHOR]

Error amplification (EA) feedback is a promising approach to advance visuomotor skill. As error detection and visuomotor processing at short time scales decline with age, this study examined whether older adults could benefit from EA feedback that included higher-frequency information to guide a force-tracking task. Fourteen young and 14 older adults performed low-level static isometric force-tracking with visual guidance of typical visual feedback and EA feedback containing augmented high-frequency errors. Stabilogram diffusion analysis was used to characterize force fluctuation dynamics. Also, the discharge behaviors of motor units and pooled motor unit coherence were assessed following the decomposition of multi-channel surface electromyography (EMG). EA produced different behavioral and neurophysiological impacts on young and older adults. Older adults exhibited inferior task accuracy with EA feedback than with typical visual feedback, but not young adults. Although stabilogram diffusion analysis revealed that EA led to a significant decrease in critical time points for both groups, EA potentiated the critical point of force fluctuations , short-term effective diffusion coefficients (Ds), and short-term exponent scaling only for the older adults. Moreover, in older adults, EA added to the size of discharge variability of motor units and discharge regularity of cumulative discharge rate, but suppressed the pooled motor unit coherence in the 13–35 Hz band. Virtual EA alters the strategic balance between open-loop and closed-loop controls for force-tracking. Contrary to expectations, the prevailing use of closed-loop control with EA that contained high-frequency error information enhanced the motor unit discharge variability and undermined the force steadiness in the older group, concerning declines in physiological complexity in the neurobehavioral system and the common drive to the motoneuronal pool against force destabilization.

Acute type A aortic dissection has long been a challenging issue. The surgical techniques traditionally vary with the anatomic extent of the aortic dissection. Simple ascending aortic grafting can be lifesaving, but the lesions beyond the aorta, which include the arch vessels and descending aorta, remain potential hazards. In this paper, we present a patient in which acute type A aortic dissection with lesions extending into descending thoracic aorta was successfully managed by total arch replacement with supra-aortic transposition plus the frozen elephant trunk technique to the descending aorta. A 67-year-old gentleman presented with severe tearing pain from the anterior to posterior chest. Computed tomography confirmed the diagnosis of acute type A dissection extending to the level of the right common iliac artery. An emergent operation was performed as in the aforementioned technique. The surgery went well and the patient was discharged without comorbidities on postoperative day 25. The patient had regular outpatient clinical follow-up. The follow-up computed tomography images showed adequate results with the obliteration of the false lumen. In conclusion, total aortic arch replacement with supra-aortic transposition plus frozen elephant trunk technique is a safe and feasible operative method for patients with detrimental acute type A aortic dissection.

Lead (Pb) is a heavy metal that negatively affects human health. Many studies have shown the relationship between lead exposure and various human activities, of which automobile service stations with gasoline emissions are considered the main cause. However, a limited number of studies have specifically considered lead exposure from automobile stations in Vietnam, as well as its impact on human activities and the surrounding natural resources. The objective of this study was to assess the possible risks of lead exposure to the surrounding agricultural and non-agricultural farms of a bus station located in the center of Dalat city, Lamdong province, Vietnam. To address this objective, 45 samples were collected from the soil, irrigated water resources, and vegetable crops of areas both close to and far away from the bus station. These samples were tested using the atomic absorption spectrometry technique. Our findings demonstrated higher lead concentration levels from all three types of samples collected from areas near the bus station. Of which, soil and water samples showed higher than normal exposure values of lead, but these were still under the allowed limits established by the Vietnam standard. Different from the soil and water, vegetable samples surrounding the bus station presented greater lead contamination than the permitted limit. High risk quotient (RQ) indexes were detected to point out that accumulative consumption of leaded vegetables over time could cause lead poisoning and harm human health. This study not only provides significant inferential evidence of the risk of lead exposure to agricultural activities and human health in Vietnam, but also delivers a real-life example for a real-world context.

Angiogenesis is critical in the development of cancer, which involves several angiogenic factors in its peritoneal dissemination. The role of protein tumor progression locus 2 (Tpl2) in angiogenic factor-related endothelial cell angiogenesis is still unclear. To understand the precise mechanism(s) of Tpl2 inhibition in endothelial cells, this study investigated the role of Tpl2 in mediating angiogenic signals using in vitro, in vivo, and ex vivo models. Results showed that inhibition of Tpl2 inhibitor significantly reduced peritoneal dissemination in a mouse model by positron emission tomography/computed tomography imaging. Simultaneously, inhibiting Tpl2 blocked angiogenesis in tumor nodules and prevented angiogenic factor-induced proliferating cell nuclear antigen (PCNA) in endothelial cells. Vascular endothelial growth factor (VEGF) or chemokine (C-X-C motif) ligand 1 (CXCL1) increased Tpl2 kinase activity and phosphorylation in a dose- and time-dependent manner. Furthermore, Tpl2 inhibition or ablation by siRNA prevented the angiogenic signal-induced tube formation in Matrigel plug assay or aortic ring assay. Inhibiting Tpl2 also prevented the angiogenic factor-induced chemotactic motility and migration of endothelial cells. Tpl2 inhibition by CXCL1 or epidermal growth factor in endothelial cells was associated with inactivation of CCAAT/enhancer binding protein β, nuclear factor κ light-chain enhancer of activated B cells, and activating protein 1 and suppression of VEGF expression. Thus, Tpl2 inhibitors thwart Tpl2-regulated VEGF by inactivating transcription factors involved in angiogenic factor-triggered endothelial cell angiogenesis. These results suggest that the therapeutic inhibition of Tpl2 may extend beyond cancer and include the treatment of other diseases involving pathologic angiogenesis.

Diabetes mellitus has been recognized since antiquity. It currently affects as many as 285 million people worldwide and results in heavy personal and national economic burdens. Considerable progress has been made in orthodox antidiabetic drugs. However, new remedies are still in great demand because of the limited efficacy and undesirable side effects of current orthodox drugs. Nature is an extraordinary source of antidiabetic medicines. To date, more than 1200 flowering plants have been claimed to have antidiabetic properties. Among them, one-third have been scientifically studied and documented in around 460 publications. In this review, we select and discuss blood glucose-lowering medicinal herbs that have the ability to modulate one or more of the pathways that regulate insulin resistance, β-cell function, GLP-1 homeostasis, and glucose (re)absorption. Emphasis is placed on phytochemistry, anti-diabetic bioactivities, and likely mechanism(s). Recent progress in the understanding of the biological actions, mechanisms, and therapeutic potential of compounds and extracts of plant origin in type 2 diabetes is summarized. This review provides a source of up-to-date information for further basic and clinical research into herbal therapy for type 2 diabetes. Emerging views on therapeutic strategies for type 2 diabetes are also discussed. [ABSTRACT FROM AUTHOR]

Background: Honokiol, a small-molecular weight natural product, has previously been reported to activate apoptosis and inhibit gastric tumorigenesis. Whether honokiol inhibits the angiogenesis and metastasis of gastric cancer cells remains unknown. Methodology/Principal Findings: We tested the effects of honokiol on angiogenic activity and peritoneal dissemination using in vivo, ex vivo and in vitro assay systems. The signaling responses in human gastric cancer cells, human umbilical vascular endothelial cells (HUVECs), and isolated tumors were detected and analyzed. In a xenograft gastric tumor mouse model, honokiol significantly inhibited the peritoneal dissemination detected by PET/CT technique. Honokiol also effectively attenuated the angiogenesis detected by chick chorioallantoic membrane assay, mouse matrigel plug assay, rat aortic ring endothelial cell sprouting assay, and endothelial cell tube formation assay. Furthermore, honokiol effectively enhanced signal transducer and activator of transcription (STAT-3) dephosphorylation and inhibited STAT-3 DNA binding activity in human gastric cancer cells and HUVECs, which was correlated with the up-regulation of the activity and protein expression of Src homology 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1). Calpain-II inhibitor and siRNA transfection significantly reversed the honokiol- induced SHP-1 activity. The decreased STAT-3 phosphorylation and increased SHP-1 expression were also shown in isolated peritoneal metastatic tumors. Honokiol was also capable of inhibiting VEGF generation, which could be reversed by SHP-1 siRNA transfection. Conclusions/Significance: Honokiol increases expression and activity of SPH-1 that further deactivates STAT3 pathway. These findings also suggest that honokiol is a novel and potent inhibitor of angiogenesis and peritoneal dissemination of gastric cancer cells, providing support for the application potential of honokiol in gastric cancer therapy. [ABSTRACT FROM AUTHOR]