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Background As COVID-19 continues to spread around the world, understanding how patterns of human mobility and connectivity affect outbreak dynamics, especially before outbreaks establish locally, is critical for informing response efforts. In Taiwan, most cases to date were imported or linked to imported cases. Methods In collaboration with Facebook Data for Good, we characterized changes in movement patterns in Taiwan since February 2020, and built metapopulation models that incorporate human movement data to identify the high risk areas of disease spread and assess the potential effects of local travel restrictions in Taiwan. Results We found that mobility changed with the number of local cases in Taiwan in the past few months. For each city, we identified the most highly connected areas that may serve as sources of importation during an outbreak. We showed that the risk of an outbreak in Taiwan is enhanced if initial infections occur around holidays. Intracity travel reductions have a higher impact on the risk of an outbreak than intercity travel reductions, while intercity travel reductions can narrow the scope of the outbreak and help target resources. The timing, duration, and level of travel reduction together determine the impact of travel reductions on the number of infections, and multiple combinations of these can result in similar impact. Conclusions To prepare for the potential spread within Taiwan, we utilized Facebook’s aggregated and anonymized movement and colocation data to identify cities with higher risk of infection and regional importation. We developed an interactive application that allows users to vary inputs and assumptions and shows the spatial spread of the disease and the impact of intercity and intracity travel reduction under different initial conditions. Our results can be used readily if local transmission occurs in Taiwan after relaxation of border control, providing important insights into future disease surveillance and policies for travel restrictions.

Identifying sources and sinks of malaria transmission is critical for designing effective intervention strategies particularly as countries approach elimination. The number of malaria cases in Thailand decreased 90% between 2012 and 2020, yet elimination has remained a major public health challenge with persistent transmission foci and ongoing importation. There are three main hotspots of malaria transmission in Thailand: Ubon Ratchathani and Sisaket in the Northeast; Tak in the West; and Yala in the South. However, the degree to which these hotspots are connected via travel and importation has not been well characterized. Here, we develop a metapopulation model parameterized by mobile phone call detail record data to estimate parasite flow among these regions. We show that parasite connectivity among these regions was limited, and that each of these provinces independently drove the malaria transmission in nearby provinces. Overall, our results suggest that due to the low probability of domestic importation between the transmission hotspots, control and elimination strategies can be considered separately for each region.

Background Malaria transmission in the Chittagong Hill Tracts (CHT) districts in Bangladesh is characterized by considerable heterogeneity in incidence and the frequent mixing and importation of parasites across districts. Thus, elimination efforts must account for human mobility between endemic and non-endemic locations, and the relative importance of local transmission and parasite importation domestically. Methods We construct a metapopulation malaria model, parameterized by human mobility data and fit to epidemiological data, to guide elimination efforts in the region. Results We find substantial heterogeneity in the transmission intensity across the CHT, with the estimated basic reproduction number varying greatly across places with similar levels of observed incidence. When vector control interventions are applied locally, the greatest impact in reducing overall incidence are in places with both high transmission intensity and high connectivity with more populated districts in the western part of the CHT. Conclusions Local elimination in several areas with low or intermediate incidence has a moderate impact in reducing overall incidence, indicating that only focusing on high incidence areas is not sufficient for malaria elimination. More generally, our modeling framework can be used to prioritize resource allocation and identify the conditions necessary for malaria elimination in the region. Plain Language Summary Malaria can be hard to eliminate because people move between regions. This movement can carry parasites from areas with high transmission (“source” regions) into areas with lower transmission (“sink” regions). We built a mathematical model of malaria in Bangladesh that combines human movement patterns with disease data. We found that elimination works best when control efforts target areas that have both high malaria transmission and strong connections to larger, more populated districts. Focusing only on areas with high numbers of cases is not enough to achieve elimination. Our model can facilitate public health decisions on where to focus resources and what conditions are needed to achieve malaria elimination in Bangladesh. Mahmud, Chang et al., model malaria transmission encompassing human mobility and epidemiological data in Bangladesh to guide elimination efforts. Local vector control efforts have the greatest impact when targeted to places with both high transmission intensity and high connectivity.

The escalating number of dengue virus (DENV) outbreaks and their worldwide spread pose a major threat to global public health. DENV transmission dynamics significantly influence outbreak duration and magnitude. Conventional DENV transmission requires an incubation period between mosquitoes biting infected humans and the mosquitoes becoming infectious. However, the possibility of immediate, mechanical transmission of DENV without viral replication in the mosquito has received little attention despite its potential importance. Here, we show that Aedes aegypti mosquitoes can mechanically transmit DENV to susceptible mice immediately after biting infected mice without the need for an incubation period. By incorporating parameters from our experiments into a newly developed mathematical model, we found a significant impact on DENV outbreak characteristics. Mechanical transmission may amplify existing disease transmission routes and influence outbreak dynamics. Our findings have implications for vector control strategies that target mosquito lifespan and suggest the possibility of similar mechanical transmission routes in other disease-carrying mosquitoes.Competing Interest StatementThe authors have declared no competing interest.

LM23, a gene expressed specifically in the testis in a stage-specific manner, has a diverse range of functions that are important in both the life and death of spermatogenic cells. The aim of this study was to further investigate the expression of LM23 in the developing rat testis and the biological function of LM23 in proliferation and antiapoptosis in vitro. Semiquantitative reverse transcription （RT）-PCR and real-time PCR were used to examine the expression of LM23 in testis at different developmental stages. The results suggested that LM23 mRNA levels in the testis increased progressively after birth. The role of LM23 in proliferation was analyzed with cell counting kit-8 （CCK8）, colony-forming efficiency （CFE） and flow cytometry assays. The results indicated that ectopic expression of LM23 in 293T cells significantly promoted cell proliferation by increasing cell numbers in S phase. Several methods were used, including CCK8, annexin V and propidium iodide staining and western blotting, to determine the role of LM23 in apoptosis. The results showed that LM23 played a protective role in H202-induced apoptosis of 293T cells, mediated at least in part through the Akt/PI3K signal pathway. Taken together, these results provide new insights into the role of LM23 in the development of the testes andspermatogenesis.

Geniposide is an iridoid glycosides purified from the fruit of Gardenia jasminoides Ellis, which is known to have antiinflammatory, anti- oxidative and anti-tumor activities. The present study aimed to investigate the effects of geniposide on experimental rat colitis and to reveal the related mechanisms, Experimental rat colitis was induced by rectal administration of a TNBS solution. The rats were treated with geniposide （25, 50 mg.kg-1.d-1, ig） or with sulfasalazine （SASP, 100 mg.kg-1.d-1, ig） as positive control for 14 consecutive days. A Caco-2 cell monolayer exposed to lipopotysaccharides （LPS） was used as an epithelial barrier dysfunction model. Transepithelial electrical resistance （TER） was measured to evaluate intestinal barrier function. In rats with TNBS-induced colitis, administration of geniposide or SASP significantly increased the TNBS-decreased body weight and ameliorated TNBS-induced experimental colitis and related symptoms. Geniposide or SASP suppressed inflammatory cytokine （TNF-α, IL-1β, and IL-6） release and neutrophil infiltration （myeloperoxidase activity） in the colon. In Caco-2 ceils, geniposide （25-100 pg/mL） ameliorated LPS-induced endothelial barrier dysfunction via dose-dependently increasing transepithelial electrical resistance （TER）. The results from both in vivo and in vitro studies revealed that geniposide down-regulated NF-KB, COX-2, iNOS and MLCK protein expression, up-regulated the expression of tight junction proteins （occludin and ZO-1）, and facilitated AMPK phosphorylation. Both AMPK siRNA transfection and AMPK overexpression abrogated the geniposide-reduced MLCK protein expression, suggesting that geniposide ameliorated barrier dysfunction via AMPK- mediated inhibition of the MLCK pathway. In conclusion, geniposide ameliorated TNBS-induced experimental rat colitis by both reducing inflammation and modulating the disrupted epithelial barrier function via activating the AMPK signaling pathway.

Local anesthetics are frequently used in fine-needle aspiration of thyroid lesions and locoregional control of persistent or recurrent thyroid cancer. Recent evidence suggests that local anesthetics have a broad spectrum of effects including inhibition of cell proliferation and induction of apoptosis in neuronal and other types of cells. In this study, we demonstrated that treatment with lidocaine and bupivacaine resulted in decreased cell viability and colony formation of both 8505C and K1 cells in a dose-dependent manner. Lidocaine and bupivacaine induced apoptosis, and necrosis in high concentrations, as determined by flow cytometry. Lidocaine and bupivacaine caused disruption of mitochondrial membrane potential and release of cytochrome c, accompanied by activation of caspase 3 and 7, PARP cleavage, and induction of a higher ratio of Bax/Bcl-2. Based on microarray and pathway analysis, apoptosis is the prominent transcriptional change common to lidocaine and bupivacaine treatment. Furthermore, lidocaine and bupivacaine attenuated extracellular signal-regulated kinase 1/2 (ERK1/2) activity and induced activation of p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase. Pharmacological inhibitors of MAPK/ERK kinase and p38 MAPK suppressed caspase 3 activation and PARP cleavage. Taken together, our results for the first time demonstrate the cytotoxic effects of local anesthetics on thyroid cancer cells and implicate the MAPK pathways as an important mechanism. Our findings have potential clinical relevance in that the use of local anesthetics may confer previously unrecognized benefits in the management of patients with thyroid cancer.

Background Increasing evidence indicates a pathogenic role of deregulated autophagy in rheumatoid arthritis (RA). We examined the relationship between autophagy and inflammatory parameters in patients with RA receiving biologic therapy. Methods In 72 patients with RA and 20 healthy control subjects (HC), autophagosome levels were determined by the mean fluorescence intensity (MFI) of autophagosomotropic dye incorporated into circulating immune cells, and p62 expression levels in immune cells were measured by flow cytometry. We used immunoblotting to examine protein expression of LC3-II and p62 in peripheral blood mononuclear cells. Results Patients with RA had significantly higher levels of autophagosome reflected by MFI of Cyto-ID in circulating lymphocytes, monocytes, and granulocytes (median values, 3.6, 11.6, and 64.8, respectively) compared with HC (1.9, 6.0, and 35.8; respectively) (all p  < 0.001). p62 MFI levels in lymphocytes and granulocytes from patients with RA (17.1 and 8.6, respectively) were significantly lower than those in the corresponding cells from HC (20.2, p  < 0.05; and 13.1, p  < 0.001, respectively). Significantly higher levels of LC3-II protein expression in contrast to lower p62 protein levels were observed in patients with RA than in HC. The autophagosome levels in immune cells were significantly correlated with inflammatory parameters in patients with RA, and they were significantly decreased with disease remission after treatment with tumor necrosis factor-α inhibitors or interleukin-6 receptor inhibitor. Conclusion s Elevated autophagy with significant correlation to inflammation suggests the involvement of autophagy in RA pathogenesis. The effectiveness of biologic therapy might be partly related to the downregulation of autophagy expression.

This study reports on the optimization of the extraction conditions of cordycepin from Cordyceps militaris by using ultrasonication. For this purpose, the orthogonal experimental design was used to investigate the effects of factors on the ultrasonic-assisted extraction (UAE). Four factors: extraction time (min), ethanol concentration (%), extraction temperature (°C) and extraction frequency (kHz), were studied. The results showed that the highest cordycepin yield of 7.04 mg/g (86.98% ± 0.23%) was obtained with an extraction time of 60 min, ethanol concentration of 50%, extraction temperature of 65 °C and extraction frequency of 56 kHz. It was found that the cordycepin extraction yield increased with the effect of ultrasonication during the extraction process. Therefore, UAE can be used as an alternative to conventional immersion extraction with respect to the recovery of cordycepin from C. militaris, with the advantages of shorter extraction time and reduced solvent consumption.

This study investigated the psychological impact on, coping behaviors of, and traumatic stress experienced by healthcare workers during the early stage of the COVID-19 pandemic and formulated effective support strategies that can be implemented by hospitals and government policymakers to help healthcare staff overcome the pandemic. This cross-sectional study recruited clinical healthcare workers at a regional hospital in Nantou County, Taiwan. The questionnaire collected personal characteristics, data on the impact and coping behaviors of the pandemic, and Impact of Event Scale-Revised (IES-R). A total of 354 valid questionnaires were collected. The statistical methods employed were univariate and multivariate stepwise regression, and logistic regression. Perceived impact and coping behaviors were found to be moderate in degree, and traumatic stress was lower than that in other countries. However, our data identified the following subgroups that require special attention: those with young age, those living with minor children, nurses, those with self-rated poor mental health, and those with insufficient COVID-19-related training. Managers should pay particular attention to helping healthcare workers in high-risk groups, strengthen COVID-19 training, provide adequate protective equipment and shelter, and offer psychological counseling.