Highly homologous miR-135a and miR-135b converting non-small cell lung cancer from suppression to progression via enhancer switching.

microRNAs (miRNAs) are short non-coding RNAs that have been increasingly recognized for their significant roles in the progression of cancer. Distinct miRNAs exhibit diverse functions attributed to variations in their sequences. As a result of possessing highly homologous seed sequences, these miRNAs target overlapping or similar gene sets, thus performing analogous roles. However, different from this sight, our study discovered that miR-135a-5p and miR-135b-5p, despite differing by only one nucleotide, exhibit distinct functional roles. Using non-small cell lung cancer (NSCLC) as a paradigm, our findings unveiled the downregulation of miR-135a-5p and upregulation of miR-135b-5p within NSCLC through TCGA database. Consequently, we further investigated their functional differences in A549 cells. Overexpression of miR-135b-5p enhanced the proliferation and migration capabilities of A549 cells, whereas miR-135a-5p transfection exhibited the opposite effect. We demonstrated that the activation of specific enhancers serves as a crucial mechanism underlying the disparate functions exerted by miR-135a-5p and miR-135b-5p in the context of NSCLC, consequently instigating a shift from inhibition to activation in NSCLC progression. Finally, we validated through animal experiments that miR-135b-5p promoted tumor progression, while miR-135a-5p exerted inhibitory effects on NSCLC development. This study offers a novel perspective for researchers to elucidate functional disparities exhibited by highly homologous miRNAs (miR-135a-5p and miR-135b-5p) in the context of NSCLC, along with the transition from inhibitory to progressive states in NSCLC. This study provides a solid foundation for future investigations into the functional roles of highly homologous miRNAs in pathological situation.

PCDHGB7 hypermethylation-based Cervical cancer Methylation (CerMe) detection for the triage of high-risk human papillomavirus-positive women: a prospective cohort study.

BACKGROUND: Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women. METHODS: A total of 3251 hrHPV-positive women aged 30-82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated. RESULTS: CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 -) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%). CONCLUSIONS: PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals. TRIAL REGISTRATION: ChiCTR2100048972. Registered on 19 July 2021.

Hypermethylated TAGMe as a universal-cancer-only methylation marker and its application in diagnosis and recurrence monitoring of urothelial carcinoma.

BACKGROUND: Urothelial carcinoma (UC) is the second most common urological malignancy. Despite numerous molecular markers have been evaluated during the past decades, no urothelial markers for diagnosis and recurrence monitoring have shown consistent clinical utility. METHODS: The methylation level of tissue samples from public database and clinical collected were analyzed. Patients with UC and benign diseases of the urinary system (BUD) were enrolled to establish TAGMe (TAG of Methylation) assessment in a training cohort (n = 567) using restriction enzyme-based bisulfite-free qPCR. The performance of TAGMe assessment was further verified in the validation cohort (n = 198). Urine samples from 57 UC patients undergoing postoperative surveillance were collected monthly for six months after surgery to assess the TAGMe methylation. RESULTS: We identified TAGMe as a potentially novel Universal-Cancer-Only Methylation (UCOM) marker was hypermethylated in multi-type cancers and investigated its application in UC. Restriction enzyme-based bisulfite-free qPCR was used for detection, and the results of which were consistent with gold standard pyrosequencing. Importantly, hypermethylated TAGMe showed excellent sensitivity of 88.9% (95% CI: 81.4-94.1%) and specificity of 90.0% (95% CI: 81.9-95.3%) in efficiently distinguishing UC from BUD patients in urine and also performed well in different clinical scenarios of UC. Moreover, the abnormality of TAGMe as an indicator of recurrence might precede clinical recurrence by three months to one year, which provided an invaluable time window for timely and effective intervention to prevent UC upstaging. CONCLUSION: TAGMe assessment based on a novel single target in urine is effective and easy to perform in UC diagnosis and recurrence monitoring, which may reduce the burden of cystoscopy. Trial registration ChiCTR2100052507. Registered on 30 October 2021.

UHRF1 regulates alternative splicing by interacting with splicing factors and U snRNAs in a H3R2me involved manner.

The well-established functions of UHRF1 converge to DNA biological processes, as exemplified by DNA methylation maintenance and DNA damage repair during cell cycles. However, the potential effect of UHRF1 on RNA metabolism is largely unexplored. Here, we revealed that UHRF1 serves as a novel alternative RNA splicing regulator. The protein interactome of UHRF1 identified various splicing factors. Among them, SF3B3 could interact with UHRF1 directly and participate in UHRF1-regulated alternative splicing events. Furthermore, we interrogated the RNA interactome of UHRF1, and surprisingly, we identified U snRNAs, the canonical spliceosome components, in the purified UHRF1 complex. Unexpectedly, we found H3R2 methylation status determines the binding preference of U snRNAs, especially U2 snRNAs. The involvement of U snRNAs in UHRF1-containing complex and their binding preference to specific chromatin configuration imply a finely orchestrated mechanism at play. Our results provided the resources and pinpointed the molecular basis of UHRF1-mediated alternative RNA splicing, which will help us better our understanding of the physiological and pathological roles of UHRF1 in disease development.

Reactivation of tumour suppressor in breast cancer by enhancer switching through NamiRNA network.

Dysfunction of Tumour Suppressor Genes (TSGs) is a common feature in carcinogenesis. Epigenetic abnormalities including DNA hypermethylation or aberrant histone modifications in promoter regions have been described for interpreting TSG inactivation. However, in many instances, how TSGs are silenced in tumours are largely unknown. Given that miRNA with low expression in tumours is another recognized signature, we hypothesize that low expression of miRNA may reduce the activity of TSG related enhancers and further lead to inactivation of TSG during cancer development. Here, we reported that low expression of miRNA in cancer as a recognized signature leads to loss of function of TSGs in breast cancer. In 157 paired breast cancer and adjacent normal samples, tumour suppressor gene GPER1 and miR-339 are both downregulated in Luminal A/B and Triple Negative Breast Cancer subtypes. Mechanistic investigations revealed that miR-339 upregulates GPER1 expression in breast cancer cells by switching on the GPER1 enhancer, which can be blocked by enhancer deletion through the CRISPR/Cas9 system. Collectively, our findings reveal novel mechanistic insights into TSG dysfunction in cancer development, and provide evidence that reactivation of TSG by enhancer switching may be a promising alternative strategy for clinical breast cancer treatment.

Circulation of genotypes of dengue virus serotype 2 in Guangzhou over a period of 20 years.

BACKGROUND: The dengue epidemic in Guangzhou has imposed a rising burden on society and health infrastructure. Here, we present the genotype data for dengue virus serotype 2 (DENV-2) to improve understanding of this dengue epidemic. METHODS: We sequenced the envelope gene of DENV-2 obtained from patient serum samples and subsequently performed maximum-likelihood phylogenetic analysis using PhyMLv3.1, maximum clade credibility analysis using BEAST v.1.10.4, and selection pressure analysis using Datamonkey 2.0. RESULTS: The prevalent DENV-2 strains identified in Guangzhou region are related to those in Southeast Asian countries. In particular, the Malaysia/Indian subcontinent genotype is prevailing in Guangzhou with no apparent genotype shift having occurred over the past 20 years. However, episodic positive selection was detected at one site. CONCLUSIONS: Local control of the DENV-2 epidemic in Guangzhou requires effective measures to prevent and monitor imported cases. Moreover, the shift between the Malaysia/Indian subcontinent genotype lineages, which originated at different time points, may account for the rise in DENV-2 cases in Guangzhou. Meanwhile, the low rate of dengue haemorrhagic fever in Guangzhou may be explained by the dominance of the less virulent Malaysia/Indian subcontinent genotype.

Association between residential greenness and overweight/obesity among rural adults in northwestern China.

BACKGROUND: Living in greener areas may reduce adiposity, but epidemiological evidence on this topic is still inconsistence and limited, especially in rural areas. METHODS: We performed a cross-sectional study among 4651 Uyghur adults in rural areas in Xinjiang province, northwestern China, from May to September 2016. We measured residential greenness levels using satellite-derived Normalized Difference Vegetation Index (NDVI) and Soil Adjusted Vegetation Index (SAVI) in 100 m, 300 m, 500 m, and 1000 m buffers around each home address. Body height, weight, and waist circumference were assessed according to recommended guidelines. Data on baseline characteristics and confounders were collected using a questionnaire. We used generalized linear mixed models to estimate the associations of residential greenness with overweight/obesity prevalence and obesity-related anthropometric indices. RESULTS: Higher residential greenness levels were associated with lower waist circumference and body mass index levels, as well as with a lower odds ratio of peripheral overweight/obesity prevalence. No significant association was found for greenness and central obesity prevalence. The associations persisted in magnitude and direction across several sensitivity analyses we performed. Stratified analysis suggested that the associations were generally stronger in older adults than those in younger adults. Additionally, neither air pollutants nor physical activity significantly mediated the associations between greenness and obesity. CONCLUSIONS: Our results suggest that higher residential greenness were associated with lower odds of overweight/obesity and lower obesity-related anthropometric indices among rural Uyghur adults in China, especially for older adults.

Sewage as a Possible Transmission Vehicle During a Coronavirus Disease 2019 Outbreak in a Densely Populated Community: Guangzhou, China, April 2020.

BACKGROUND: Sewage transmission of SARS-CoV-2 has never been demonstrated. During a COVID-19 outbreak in Guangzhou, China in April 2020, we investigated the mode of transmission. METHODS: We collected clinical and environmental samples from quarantined residents and their environment for RT-PCR testing and genome sequencing. A case was a resident with a positive RT-PCR test regardless of symptoms. We conducted a retrospective cohort study of all residents of cases' buildings to identify risk factors. RESULTS: We found 8 cases (onset: 5-21 April). During incubation period, cases 1 and 2 frequented market T where a COVID-19 outbreak was ongoing; cases 3-8 never visited market T, lived in separate buildings and never interacted with cases 1 and 2. Working as a janitor or wastepicker (RR = 13; 95% CIexact, 2.3-180), not changing to clean shoes (RR = 7.4; 95% CIexact, 1.8-34) and handling dirty shoes by hand (RR = 6.3; 95% CIexact, 1.4-30) after returning home were significant risk factors. RT-PCR detected SARS-CoV-2 in 19% of 63 samples from sewage puddles or pipes, and 24% of 50 environmental samples from cases' apartments. Viruses from the squat toilet and shoe-bottom dirt inside the apartment of cases 1 and 2 were homologous with those from cases 3-8 and the sewage. Sewage from the apartment of cases 1 and 2 leaked out of a cracked pipe onto streets. Rainfall after the onset of cases 1 and 2 flooded the streets. CONCLUSIONS: SARS-CoV-2 might spread by sewage, highlighting the importance of sewage management during outbreaks.

Transmission dynamics of SARS-CoV-2 in a mid-size city of China.

BACKGROUND: An outbreak of pneumonia, COVID-19 associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan city and then rapidly spread to other cities. Wenzhou is located approximately 900 km from Wuhan, which was experiencing an outbreak that was severe at the time but is considered modest as the epidemic became a pandemic. We described the epidemiological characteristics of SARS-CoV-2 outside of the epicenter to help understand the transmission pattern in a mid-sized Chinese city. METHODS: To investigate the epidemiological and clinical characteristics of the COVID-19, we described case series of 473 patients with confirmed COVID-19 in Wenzhou, China from January 27 to March 16, 2020. We described the public health interventions of COVID-19 and evaluated the effect of interventions by the effective reproduction number (Rt). RESULTS: The median age of all patients was 47.6 years, 48.4% of whom were female. 33.8% of the patients had a history of residence in Wuhan. Fever (71.7%) and cough (43.1%) were the most common symptoms. In addition, three kinds of unconventional cases were observed, namely 4.9% asymptomatic patients, 7.6% confirmed patients who had no link to Wuhan city but contact with individuals from Wuhan without any symptoms at the time of contact, and 12.9% confirmed patients who had an unknown source of transmission. We estimated that the basic reproductive number (R0) was 2.75 (95% CI: 2.37-3.23). The Rt fluctuated within the range of 2.50 to 3.74 from January 11 to January 16 while gradually reached a peak of 3.74 on January 16. Rt gradually decreased after January 16 and decreased to 1.00 on January 30. Rt continually decreased and reached the lowest point (0.03) on February 21, 2020. CONCLUSION: Our study presented the possibility of asymptomatic carriers affected with SARS-CoV-2, and transmission by these three kinds of unconventional patients in Wenzhou may be an important characteristic of SARS-CoV-2 transmission. The evaluation showed that a series of multifaceted interventions proved effective in controlling the epidemic of COVID-19. These findings might provide valuable examples of control policies for countries or areas in combatting the global pandemic of COVID-19.

COVID-19 Outbreak Associated with Air Conditioning in Restaurant, Guangzhou, China, 2020.

During January 26-February 10, 2020, an outbreak of 2019 novel coronavirus disease in an air-conditioned restaurant in Guangzhou, China, involved 3 family clusters. The airflow direction was consistent with droplet transmission. To prevent the spread of the virus in restaurants, we recommend increasing the distance between tables and improving ventilation.

Effects of dairy products, calcium and vitamin D on ovarian cancer risk: a meta-analysis of twenty-nine epidemiological studies.

Findings for the roles of dairy products, Ca and vitamin D on ovarian cancer risk remain controversial. We aimed to assess these associations by using an updated meta-analysis. Five electronic databases (e.g. PubMed and Embase) were searched from inception to 24 December 2019. Pooled relative risks (RR) with 95 % CI were calculated. A total of twenty-nine case-control or cohort studies were included. For comparisons of the highest v. lowest intakes, higher whole milk intake was associated with increased ovarian cancer risk (RR 1·35; 95 % CI 1·15, 1·59), whereas decreased risks were observed for higher intakes of low-fat milk (RR 0·84; 95 % CI 0·73, 0·96), dietary Ca (RR 0·71; 95 % CI 0·60, 0·84) and dietary vitamin D (RR 0·80; 95 % CI 0·67, 0·95). Additionally, for every 100 g/d increment, increased ovarian cancer risks were found for total dairy products (RR 1·03; 95 % CI 1·01, 1·04) and for whole milk (RR 1·07; 95 % CI 1·03, 1·11); however, decreased risks were found for 100 g/d increased intakes of low-fat milk (RR 0·95; 95 % CI 0·91, 0·99), cheese (RR 0·87; 95 % CI 0·76, 0·98), dietary Ca (RR 0·96; 95 % CI 0·95, 0·98), total Ca (RR 0·98; 95 % CI 0·97, 0·99), dietary vitamin D (RR 0·92; 95 % CI 0·87, 0·97) and increased levels of circulating vitamin D (RR 0·84; 95 % CI 0·72, 0·97). These results show that whole milk intake might contribute to a higher ovarian cancer risk, whereas low-fat milk, dietary Ca and dietary vitamin D might reduce the risk.

Magnetic porous aromatic framework with a core-shell structure as a sorbent for rapid extraction of phenols and their quantitation in urine by HPLC-UV.

A porous aromatic framework (PAF) is shown to be a viable sorbent for the adsorption of phenols. To overcome the difficulty of quick adsorption and enrichment by phenols from the matrix, a sorbent material consisting of porous aromatic framework magnetic nanoparticles (PAF MNPs) with a core-shell structure was fabricated by an in situ growth method. The PAF MNP sorbent was characterized by transmission electron microscopy, Fourier transform infrared spectroscopy and other techniques. The factors affecting enrichment performance including the amount of PAF-6 MNPs, sample pH, extraction time and elution conditions were optimized. Under the optimal conditions, a method utilizing high-performance liquid chromatography with an ultraviolet detector (HPLC-UV) was developed to quantify phenols in urine. The method showed good linearity (r ≥ 0.998), good precision (RSD ≤ 9.9%, n = 6) and a low limit of detection (1.0-2.0 ng/mL, S/N = 3), with recoveries performed in urine matrix ranging from 76.7% to 113.2%. The method is simple, time-saving and sensitive. Moreover, compared with traditional mass spectrometry detection methods, this method has advantages in terms of low cost and repeatability. Graphical abstract.

An outbreak of norovirus-related acute gastroenteritis associated with delivery food in Guangzhou, southern China.

BACKGROUND: A large number of students at a school in Guangzhou city developed a sudden onset of symptoms of diarrhea and vomiting. To help control the outbreak, we conducted an epidemiological investigation to determine the causative agent, sources, role of transmission and risk factors of the infections. METHODS: The study population consisted of probable and confirmed cases. An active search was conducted for cases among all students, teachers and other school staff members. A case control study was carried out using standardized online questionnaires. Data were obtained regarding demographic characteristics, gastrointestinal symptoms, personal hygiene habits, history of contact with a person who had diarrhea and/or vomiting and dining locations during the past 3 days. Rectal swabs or stool samples of the cases and, food handlers, as well as environmental samples were collected to detect potential intestinal viruses and bacteria. We calculated odds ratios and 95% confidence intervals (CIs). RESULTS: A total of 157 individuals fit the definition of a probable case, including 46 with laboratory-confirmed norovirus infection between March 8 and March 22, 2018. The proportion of students who had eaten delivery food 3 days before the onset of illness in the case group was 2.69 times that in the control group (95%CI: 1.88-3.85). Intake of take-out food 3 days earlier, and exposure to similar cases 72 h before onset and case in the same dormitory were risk factors. A total of 20 rectal swab samples from students, 10 rectal swabs from food handlers and 2 environmental swab samples from the out-campus restauranttested positive for norovirus (GII, genogroup II strain). CONCLUSIONS: We investigated an outbreak of norovirus infectious diarrhea. Food handling practices carry potential risk of acute gastroenteritis outbreaks owing to a lack of surveillance and supervision. Greater attention should be paid to the monitoring and supervision of food handlers in off campus restaurant to reduce the incidence of norovirus-related acute gastroenteritis associated with delivery food.

Climate variation drives dengue dynamics.

Dengue, a viral infection transmitted between people by mosquitoes, is one of the most rapidly spreading diseases in the world. Here, we report the analyses covering 11 y (2005-2015) from the city of Guangzhou in southern China. Using the first 8 y of data to develop an ecologically based model for the dengue system, we reliably predict the following 3 y of dengue dynamics-years with exceptionally extensive dengue outbreaks. We demonstrate that climate conditions, through the effects of rainfall and temperature on mosquito abundance and dengue transmission rate, play key roles in explaining the temporal dynamics of dengue incidence in the human population. Our study thus contributes to a better understanding of dengue dynamics and provides a predictive tool for preventive dengue reduction strategies.

Canine rabies control and human exposure 1951-2015, Guangzhou, China.

OBJECTIVE: To describe changes in rabies surveillance and management in Guangzhou, China between 1951 and 2015, and to analyse human rabies cases over that period. METHODS: Rabies control policies and strategies implemented by the Guangzhou government were reviewed for three periods: 1951 to 1978, 1979 to 2000 and 2001 to 2015. Data on human rabies deaths and exposure were obtained from Guangzhou and national health and disease records. The demographic characteristics of human cases are reported using descriptive statistics. FINDINGS: Between 1951 and 2015, the number of organizations cooperating on rabies control increased: there were two between 1951 and 1978, six between 1979 and 2000, and nine between 2001 and 2015. The number of human rabies cases reported in these periods was 331, 422 and 60, respectively. Organizations involved included city and district centres for disease control and prevention, rabies outpatient clinics, medical institutions and police. Overall, 88% (713/813) of cases occurred in rural districts, though, between 1951 and 2015, the distribution shifted from being predominantly rural to being both urban and rural. The number of people exposed to rabies increased annually. The biggest increases were among those injured by a pet dog or other animal: 3.26 and 4.75 times, respectively, between 2005 and 2015. CONCLUSION: Increased cooperation on rabies control between civil organizations in Guangzhou over decades was associated with a marked decrease in the number of human rabies cases. The Guangzhou experience could thereby provide guidance for other cities experiencing similar rabies epidemics.

The increasing menace of dengue in Guangzhou, 2001-2016: the most important epicenter in mainland China.

BACKGROUND: Dengue is the most prevalent mosquito-borne disease in the world, with China affected seriously in recent years. 65.8% of dengue cases identified in mainland China since 2005 were reported from the city of Guangzhou. METHODS: In this study, we described the incidence rate and distribution of dengue cases using data collected form National Notifiable Infectious Disease Reporting Information System data in Guangzhou for 2001 to 2016. All dengue cases were investigated using standardized questionnaire. RESULTS: A total of 42,469 dengue cases were reported, with an average annual incidence rate of 20.99 per 100,000 resident population. Over this time period, the incidence rate of indigenous cases increased. Dengue affected areas also expanded sharply geographically from 58.1% of communities affected during 2001-2005 to 96.4% of communities affected in 2011-2016. Overall 95.30% of the overseas imported cases were reported during March and December, while 99.79% of indigenous cases were reported during July and November. All four dengue virus serotypes were identified both in imported cases and indigenous cases. The Aedes albopictus mosquito was the only vector for dengue transmission in the area. CONCLUSIONS: Guangzhou has become the dengue epicenter in mainland China. Control strategies for dengue should be adjusted to the epidemiological characteristics above and intensive study need to be conducted to explore the factors that driving the rapid increase of dengue.

Evaluation of the appropriate predictive contributor and diagnostic threshold for the cardio-metabolic syndrome in Chinese Uyghur adults.

BACKGROUND: Several epidemiological studies have suggested that optimal obesity and visceral adiposity indicators and their cut-off values to predict cardio-metabolic risks varied among different ethnic groups. However, few studies have investigated the associations of anthropometric indices with cardio-metabolic risks in Chinese Uyghur adults, and the results were inconsistent. METHODS: Between May and September 2016, a total of 4664 subjects aged ≥18 years old were recruited from Northwest China. Anthropometric indices and cardio-metabolic risk factors were measured by trained personnel. Partial correlation analyses and logistic regression analyses were used to evaluate the associations of anthropometric indices with cardio-metabolic risk factors. Receiver operating characteristic analysis was used to compare the abilities of different anthropometric indices to predict cardio-metabolic risk factors, and to determine the optimal cut-off values. RESULTS: The prevalence of metabolic syndrome was 39.41% in Uyghur adults from Xinjiang Uyghur Autonomous Region. Waist circumference (WC) performed better than other obesity indices in predicting the cardio-metabolic risk factors, and the optimal cut-off value of WC to diagnose metabolic syndrome risk factors was 86.50 cm for women and 90.50 cm for men. CONCLUSIONS: Our study suggests that WC had the strongest predictive power for identifying cardio-metabolic risks in Xinjiang Uyghur adults. Further well-designed longitudinal studies are needed to confirm our findings.

Antiviral activity of Carbenoxolone disodium against dengue virus infection.

As one of the most important mosquito-borne viral diseases, dengue infection is now becoming a global concern due to its rapid spread and rise in incidence. Currently, there is no approved vaccine or effective antiviral drug for dengue virus (DENV) infection. Glycyrrhetinic acid (GNa) and its related derivatives have been reported to inhibit a broad spectrum of viruses. However, it is unknown whether Carbenoxolone disodium (CBX), one of the GNa derivatives, affects DENV infection. Here, we found that the production of infectious DENV particles was significantly decreased by CBX treatment in DENV-permissive cells, while the viral RNA and viral protein synthesis were not affected. Moreover, results from time-of-addition study showed that the inhibitory effect of CBX on DENV was exhibited by targeting the virus itself, not the host cells. Directly incubating DENV with CBX resulted in a remarkable reduction of virus titer and virus infectivity. Furthermore, DENV RNA from progeny virions in the supernatants was significantly decreased by CBX treatment in a dose-dependent manner. Taken together, these data indicate that the antiviral activity of CBX against DENV may be mainly due to a virucidal effect exerted by the compound itself. Our work, for the first time, demonstrates that CBX has antiviral activity against DENV infection, providing useful information for development of potential therapeutic interventions against dengue. J. Med. Virol. 89:571-581, 2017. © 2016 Wiley Periodicals, Inc.

miR-146a Inhibits dengue-virus-induced autophagy by targeting TRAF6.

During dengue virus (DENV) infection, the virus manipulates different cellular pathways to assure productive replication, including autophagy. However, it remains unclear how this autophagic process is regulated. Here, we have demonstrated a novel role for the microRNA miR-146a in negatively regulating the cellular autophagic pathway in DENV-infected A549 cells and THP-1 cells. Overexpression of miR-146a significantly blocked DENV2-induced autophagy, and LNA-mediated inhibition of miR-146a counteracted these effects. Moreover, co-overexpression of TRAF6, a target of miR-146a, significantly reversed the inhibitory effect of miR-146a on autophagy. Notably, treatment with recombinant IFN-ß fully restored the autophagic activity in TRAF6-silenced cells. Furthermore, our data showed that, in DENV2-infected A549 cells, autophagy promoted a pro-inflammatory response to significantly increase TNF-α and IL-6 production. Taken together, our results define a novel role for miR-146a as a negative regulator of DENV-induced autophagy and identify TRAF6 as a key target of this microRNA in modulating the DENV-autophagy interaction.

Rapid increase of scrub typhus incidence in Guangzhou, southern China, 2006-2014.

BACKGROUND: In the last decade, scrub typhus (ST) has been emerging or re-emerging in some areas of Asia, including Guangzhou, one of the most affected endemic areas of ST in China. METHODS: Based on the data on all cases reported in Guangzhou from 2006 to 2014, we characterized the epidemiological features, and identified environmental determinants for the spatial distribution of ST using a panel negative binomial model. RESULTS: A total of 4821 scrub typhus cases were reported in Guangzhou during 2006-2014. The annual incidence increased noticeably and the increase was relatively high and rapid in rural townships and among elderly females. The majority of cases (86.8%) occurred during May-October, and farmers constituted the majority of the cases, accounting for 33.9% in urban and 61.6% in rural areas. The number of housekeeper patients had a rapid increment in both rural and urban areas during the study period. Atmospheric pressure and relative humidity with lags of 1 or 2 months, distributions of broadleaved forest and rural township were identified as determinants for the spatiotemporal distribution of scrub typhus. CONCLUSION: Our results indicate that surveillance and public education need to be focused on the elderly farmers in rural areas covered with broadleaf forest in southern China.