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Clarifying the impact of driving forces on multi-temporal-scale (annual, quarterly and monthly) runoff changes is of great significance for watershed water resource planning. Based on monthly runoff data and meteorological data of the Jialing River (JLR) during 1982–2020, the Mann–Kendall tendency testing approach was first applied to analyze variation tendencies of multi-timescale runoff. Then, abrupt variation years of runoff were determined using Pettitt and cumulative anomaly mutation testing approaches. The ABCD model was employed for simulating hydrological change processes in the base period and variation period. Finally, influences of climatic and anthropic factors on multi-scalar runoff were computed using the multi-scalar Budyko formula. The following conclusions were drawn in this study: (1) The mutation year of discharge was 1993; (2) the monthly runoff in the JLR presented a "single peak" distribution, and the concentration degree and concentration period in the JLR both showed an insignificant reduction trend; (3) anthropic factors were the dominant factor for spring runoff variations; climatic factors were the dominant factor on annual, summer, fall and winter runoff variations; (4) except for November, climatic factors were the dominant factor causing runoff changes in the other 11 months. This study has important reference value for water resource allocation and flood control decisions in the JLR. [ABSTRACT FROM AUTHOR]

Vegetation changes have a significant impact on the underlying surface of a watershed and alter hydrological processes. To clarify the synergistic evolution relationship between climate, vegetation, and hydrology, this study aims to reveal how vegetation restoration influences streamflow decline. This study first applied the trend-free pre-whitening Mann–Kendall (TFPW-MK) method to identify variation trends of various elements at Baihe and Shayang hydrologic stations from 1982 to 2015. Secondly, an extended Budyko equation was improved by fitting the linear relationship between annual NDVI and Budyko parameter (ω). Finally, based on the extended Budyko formula, the elastic coefficient method was applied to identify the influence of vegetation changes on runoff changes of the Baihe and Shayang stations from 1982 to 2015. The results displayed that (1) the annual NDVI of Baihe and Shayang hydrologic stations both presented an increasing trend, and streamflow presented an insignificant decrease trend. The mutation year of the annual runoff depth of Baihe and Shayang stations both occurred in 1990. (2) The annual NDVI had a significant and positive linear relationship with ω. (3) The streamflow decline of Baihe and Shayang stations is mainly influenced by precipitation variation and human activities. (4) Vegetation growth had a positive effect on the streamflow decline of Baihe and Shayang stations, with a contribution rate of 14.06% and 17.87%. This effect of vegetation growth on discharge attenuation should be given high priority. [ABSTRACT FROM AUTHOR]

Purpose: The crucial role of N6-methyladenosine (m6A) methylation in anti-tumor immunity and immunotherapy has been broadly depicted. However, the molecular phenotypic linkages between m6A modification pattern and immunological ecosystem are expected to be disentangled in hepatocellular carcinoma (HCC), for immunotherapeutic unresponsiveness circumvention and combination with promising drug agents. Methods: Modification patterns of m6A methylation were qualitatively dissected according to the large-scale HCC samples profiling. We then determined the immune phenotypic linkages by systematically evaluating their tumor microenvironment composition, immune/stromal-relevant signature, immune checkpoints correlation, and prognostic value. Individual quantification of m6A methylation pattern was achieved by m6Ascore construction, intensified by longitudinal single-cell analysis of immunotherapy cohort and validated by the transcriptomic profiles of our in-hospital GDPH-HCC cohort. Candidate therapeutic agents were also screened out. Results: Three distinct m6A methylation patterns were determined in high accordance with inflamed-, excluded-, and desert-immunophenotype. To be precise, Immune-inflamed high-m6Ascore group was characterized by activated immunity with favorable prognosis. Stromal activation and absence of immune cell infiltration were observed in low-m6Ascore phenotype, linked to impaired outcome. Patients with low-m6Ascore demonstrated diminished responses and clinical benefits for cohorts receiving immunotherapy. The above credible linkage between m6A methylation pattern and tumor immune microenvironment was robustly validated in our GDPH-HCC cohort. Single-cell dynamic change of m6A methylation level in exhausted CD8 T cell and fibroblast was depicted in immunotherapy cohort fore and art. Derived from m6A methylation pattern, seven potential frontline drug agents were recognized as promising choice for high-m6Ascore patients. Conclusion: Our work bridged the credible linkage between epigenetics and anti-tumor immunity in HCC, unraveling m6A modification pattern as immunological indicator and predictor for immunotherapy. Individualized m6Ascore facilitated strategic choices to maximize therapy-responsive possibility. [ABSTRACT FROM AUTHOR]

Pigs are well known as genetic mixing vessels for human and avian influenza viruses (1,2), and swine influenza viruses (SIVs) occasionally infect humans (3-5). SIV was first reported in humans [...]

Studying the spatial distribution characteristics of and factors that influence intangible cultural heritage is an important way to improve the management and protection of the heritage. On the basis of the standard deviation ellipse, point pattern analysis, kernel density analysis, spatial autocorrelation, Geodetector, and other methods, 891 national intangible cultural heritage artifacts (divided into five batches and ten categories) in the Yellow River Basin were taken as the research objects, and their spatial and temporal distribution characteristics and causes were quantitatively analyzed. As per the results, (1) the intangible cultural heritage in the Yellow River Basin shows a spatial distribution pattern that is dense in the east and sparse in the west, and there is a strong spatial dependence; (2) the intangible cultural heritage in the Yellow River Basin shows a "west first and then east" trend in time, and the quantity and type have significant differences in different time sections; (3) according to the batch analysis, the aggregation of the second batch of the intangible cultural heritage is the strongest, and the NNI value continues to increase from the second to the fifth batch of the intangible cultural heritage, indicating that the development of intangible cultural heritage is increasingly related to areas with backward economies and ethnic minorities; and (4) policy orientation, economic development, and topography are the dominant factors affecting the spatial distribution pattern of the intangible cultural heritage in the Yellow River Basin. [ABSTRACT FROM AUTHOR]

The shape of the hydraulic flushing hole is an important basis to determine the effective pumping radius. In the design and evaluation of the drilling hole, it is usually equivalent to a cylinder. However, the formation of the shape of the hole is affected by the gravity of coal and rock bulk, the friction of coal and rock, water force, stress, and other factors, so the scientific nature that is equivalent to a cylinder remains to be discussed. In this paper, based on the analysis of the whole process of hydraulic flushing and the formation of the pore shape, gravity, friction, water force, and ground stress of coal and rock bulk are selected as important factors affecting the pore shape, and the parallel Bergmark-Roos equation and PKN model are introduced to establish the BR-PKN equation of the pore shape of hydraulic flushing. MATLAB is used to reproduce the shape of the hydraulic flushing hole, which is a kind of ellipsoid with three different axes. In order to verify the accuracy of the hole shape, the YZD18.5 video imaging logging tool for mine lateral resistivity is used to collect and analyze the shape data of the hydraulic flushing hole, and the hole section is drawn, which is basically consistent with the theoretical derivation of the hydraulic flushing hole shape. COMSOL is used to simulate the hydraulic flushing equivalent of the ellipsoid hole compared with the cylinder hole under the same coal output and extraction time of 90 days. The extraction radius, desorption surface area, and effective extraction volume are 0.95, 0.79, and 1.14 times, respectively, providing a basis for the optimal design of hydraulic flushing. [ABSTRACT FROM AUTHOR]

Background: Timely and appropriate administration of post-exposure prophylaxis (PEP) is an essential component of human rabies prevention programs. We evaluated patient care at rabies clinics in a high-risk county in Hunan Province, China to inform strategies needed to achieve dog-mediated human rabies elimination by 2030. Methods: We collected information on PEP, staff capacity, and service availability at the 17 rabies clinics in the high-risk county during onsite visits and key staff interviews. Additionally, we conducted observational assessments at five of these clinics, identified through purposive sampling to capture real-time information on patient care during a four-week period. Wound categories assigned by trained observers were considered accurate per national guidelines for comparison purposes. We used the kappa statistic and an alpha level of 0.05 to assess agreement between observers and clinic staff. Results: In 2015, the 17 clinics provided PEP to 5,261 patients. Although rabies vaccines were available at all 17 clinics, rabies immune globulin (RIG) was only available at the single urban clinic in the county. During the assessment period in 2016, 196 patients sought care for possible rabies virus exposures. According to observers, 88 (44%) patients had category III wounds, 104 (53%) had category II wounds and 4 (2%) had category I wounds. Observers and PEP clinic staff agreed on approximately half of the assigned wound categories (kappa = 0.55, p-value< 0.001). Agreement for the urban county-level CDC clinic (kappa = 0.93, p-value<0.001) was higher than that of the rural township clinics (kappa = 0.16, p-value = 0.007). Using observer assigned wound categories, 142 (73%) patients received rabies vaccinations and RIG as outlined in the national guidelines. Conclusion: Rabies PEP services were available at each town of the project county; however, gaps between clinical practice of PEP and recommendations of national rabies guidelines were identified. We used these findings to develop and implement a training to rabies clinic staff on wound categorization, wound care, and appropriate use of PEP. Additional risk-based approaches for evaluating human rabies virus exposures may be needed as China progresses towards elimination. Author summary: Members of the United Nations agreed on a goal of eliminating dog-mediated rabies by 2030. To achieve this goal, China and other endemic rabies countries will need to increase dog rabies vaccination coverage as well as ensure proper administration of rabies post-exposure prophylaxis (PEP) for patients with animal wounds. PEP includes wound washing, timely vaccination, and rabies immune globulin (RIG) according to the type and severity of patients' wounds. The authors conducted an observational assessment of PEP clinics in a high-risk county in Hunan Province. Most patients at these clinics received PEP according to the national guidelines; however, certain patients received PEP, when not warranted, and others did not receive RIG, as recommended for severe animal wounds. Wound type categorization and corresponding use of PEP were most accurate at the single urban clinic and least accurate at the rural clinics in the project county. RIG was only available at the single urban clinic. These findings highlight the importance of improving the use of PEP and access to RIG, particularly in rural areas, and exploring the use of risk-based approaches for evaluating human rabies virus exposures. These steps can contribute to eliminating dog-mediated rabies in the project county as well as elsewhere in China. [ABSTRACT FROM AUTHOR]

Background: Hand, foot, and mouth disease (HFMD) is a global infectious disease; particularly, it has a high disease burden in China. This study was aimed to explore the temporal and spatial distribution of the disease by analyzing its epidemiological characteristics, and to calculate the early warning signals of HFMD by using a logistic differential equation (LDE) model. Methods: This study included datasets of HFMD cases reported in seven regions in Mainland China. The early warning time (week) was calculated using the LDE model with the key parameters estimated by fitting with the data. Two key time points, "epidemic acceleration week (EAW)" and "recommended warning week (RWW)", were calculated to show the early warning time. Results: The mean annual incidence of HFMD cases per 100,000 per year was 218, 360, 223, 124, and 359 in Hunan Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County across the southern regions, respectively and 60 and 34 in Jilin Province and Longde County across the northern regions, respectively. The LDE model fitted well with the reported data (R2 > 0.65, P < 0.001). Distinct temporal patterns were found across geographical regions: two early warning signals emerged in spring and autumn every year across southern regions while one early warning signals in summer every year across northern regions. Conclusions: The disease burden of HFMD in China is still high, with more cases occurring in the southern regions. The early warning of HFMD across the seven regions is heterogeneous. In the northern regions, it has a high incidence during summer and peaks in June every year; in the southern regions, it has two waves every year with the first wave during spring spreading faster than the second wave during autumn. Our findings can help predict and prepare for active periods of HFMD. Author summary: Hand, foot, and mouth disease (HFMD), a global infectious disease, has a high disease burden in China. This study aimed to explore the temporal and spatial distribution of the disease by analyzing its epidemiological characteristics and to calculate the early warning signals of HFMD by using a logistic differential equation (LDE) model. Our findings showed that 1) the HFMD disease burden in China remained high and HFMD incidence in the southern region was higher than that in the northern region; and 2) the HFMD early warnings times across China were heterogeneous. One high incidence period occurred in the northern regions during summer, peaking in June every year, while in the southern regions two waves emerged every year. Over the southern regions, the disease appeared to spread faster in the spring wave than in the autumn wave. These results provide important information for public health authorities such as the Centers for Disease Control and Prevention staff to predict and prepare for the onset of the high active periods of HFMD, especially by indicating the heterogeneous warning times of HFMD outbreak across different geographical regions in Mainland China. [ABSTRACT FROM AUTHOR]

Here we report a case study of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak event during bus trips of an index patient in Hunan Province, China. This retrospective investigation suggests potential airborne transmission of SARS-CoV-2 and the possibility of superspreading events in certain close contact and closed space settings, which should be taken into account when control strategies are planned. [ABSTRACT FROM AUTHOR]

Melanogenesis, migration and proliferation of melanocytes are important factors that determine the hair colours of mammals. MicroRNAs (miRNAs) have been shown to be closely related to these processes. In melanocytes of alpacas, insulin‐like growth factor 1 (IGF1) has been shown to improve melanogenesis through the cyclic AMP (cAMP) pathway. miR‐379 was predicted to target insulin‐like growth factor (IGF) receptor 1 (IGF1R), which binds to IGF1. Therefore, we hypothesized that miR‐379 could mediate melanogenesis, migration and proliferation of melanocytes. Here, we report that miR‐379 was highly expressed in alpaca melanocytes. Subsequent overexpression of miR‐379 in alpaca melanocytes led to the generation of the phenotype of melanogenesis, proliferation and migration. In addition, the expression of genes related to these phenotypes in melanocytes was detected. Our results showed that miR‐379 targets IGF1R in melanocytes. The overexpression of miR‐379 stimulated dendrite extension or elongation and limited the perinuclear distribution of melanin, but inhibited melanogenesis via cAMP response element (CRE)‐binding protein (CREB)/microphthalmia‐associated transcription factor (MITF) pathway. miR‐379 attenuated melanocyte migration by downregulating the focal adhesion kinase (FAK) and enhanced melanocyte proliferation by upregulating protein kinase B (AKT). These observations suggest the involvement of miR‐379 in the physiological regulation of melanocytes, mediated by targeting IGF1R on insulin receptor (IR) compensation and subsequent crosstalk. [ABSTRACT FROM AUTHOR]

Synaptotagmin‐4 (SYT4) is a membrane protein that regulates membrane traffic in neurons in a calcium‐dependent or calcium‐independent manner. In melanocytes, the intracellular free calcium ion (Ca2+) may be important for dendrite growth and melanogenesis. Mammalian melanocytes originating from neural crest cells produce melanins. Therefore, we predicted that SYT4 might play a role in melanogenesis and the dendrite morphology of melanocytes. To investigate whether SYT4 is involved in melanocyte physiology, SYT4 was overexpressed in alpaca melanocytes and B16‐F10 cells. The results showed that SYT4 overexpression resulted in a phenotype consistent with melanogenesis and dendrite extension. At the molecular level, SYT4 interacted with extracellular regulated MAP kinase (ERK) to decrease p‐ERK activity, which negatively regulated CREB expression. Furthermore, cyclic AMP‐responsive element‐binding protein (CREB) was upregulated and caused the downregulation of the expression of melanogenic regulatory proteins, including microphthalmia‐associated transcription factor (MITF), tyrosinase (TYR), tyrosinase‐related protein‐1 (TYRP1), dopachrome tautomerase (DCT), and transient receptor potential melastatin 1 (TRPM1). Intracellular free Ca2+ promoted the upregulation of calcium/calmodulin dependent protein kinase IV (CAMK4) expression, which phosphorylated CREB (p‐CREB). In turn, p‐CREB participated in the transcription of MITF. These results demonstrated that SYT4 promoted melanogenesis through dendrite extension and tyrosinase activity, during which the regulation of Ca2+ influx via the TRPM1 channel was a key factor. Significance of the study: Intracellular Ca2+ is important for the function and survival of melanocytes and melanoma cells. SYT4 stimulated melanogenesis through calcium. These results provide evidence that SYT4 regulates Ca2+ influx through TRPM1 to cause melanogenesis and axonal elongation in alpaca melanocytes and further suggesting that the growth and metastasis of melanoma is controlled by the inhibited expression of SYT4 in melanoma cells. [ABSTRACT FROM AUTHOR]

Background: Hand, foot and mouth disease (HFMD) is spread widely across Asia, and the hospitalization burden is currently not well understood. Here, we estimated serotype-specific and age-specific hospitalization rates of HFMD in Southern China. Methods: We enrolled pediatric HFMD patients admitted to 3/3 county-level hospitals, and 3/23 township-level hospitals in Anhua county, Hunan (CN). Samples were collected to identify enterovirus serotypes by RT-PCRs between October 2013 and September 2016. Information on other eligible, but un-enrolled, patients were retrospectively collected from the same six hospitals. Monthly numbers of all-cause hospitalizations were collected from each of the 23 township-level hospitals to extrapolate hospitalizations associated with HFMD among these. Results: During the three years, an estimated 3,236 pediatric patients were hospitalized with lab-confirmed HFMD, and among these only one case was severe. The mean hospitalization rate was 660 (95% CI: 638–684) per 100,000 person-years for lab-confirmed HFMD, with higher rates among CV-A16 and CV-A6 associated HFMD (213 vs 209 per 100,000 person-years), and lower among EV-A71, CV-A10 and other enterovirus associated HFMD (134, 39 and 66 per 100,000 person-years respectively, p<0.001). Children aged 12–23 months had the highest hospitalization rates (3,594/100,000 person-years), followed by those aged 24–35 months (1,828/100,000 person-years) and 6–11 months (1,572/100,000 person-years). Compared with other serotypes, CV-A6-associated hospitalizations were evident at younger ages. Conclusions: Our study indicates a substantial hospitalization burden associated with non-severe HFMD in a rural county in southern China. Future mitigation policies should take into account the disease burden identified, and optimize interventions for HFMD. [ABSTRACT FROM AUTHOR]

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused mainly by two hantaviruses in China: Hantaan virus and Seoul virus. Environmental factors can significantly affect the risk of contracting hantavirus infections, primarily through their effects on rodent population dynamics and human-rodent contact. We aimed to clarify the environmental risk factors favoring rodent-to-human transmission to provide scientific evidence for developing effective HFRS prevention and control strategies. The 10-year (2006–2015) field surveillance data from the rodent hosts for hantavirus, the epidemiological and environmental data extracted from satellite images and meteorological stations, rodent-to-human transmission rates and impacts of the environment on rodent community composition were used to quantify the relationships among environmental factors, rodent species and HFRS occurrence. The study included 709 cases of HFRS. Rodent species in Chenzhou, a hantavirus hotspot, comprise mainly Rattus norvegicus, Mus musculus, R. flavipectus and some other species (R. losea and Microtus fortis calamorum). The rodent species played different roles across the various land types we examined, but all of them were associated with transmission risks. Some species were associated with HFRS occurrence risk in forest and water bodies. R. norvegicus and R. flavipectus were associated with risk of HFRS incidence in grassland, whereas M. musculus and R. flavipectus were associated with this risk in built-on land. The rodent community composition was also associated with environmental variability. The predictive risk models based on these significant factors were validated by a good-fit model, where: cultivated land was predicted to represent the highest risk for HFRS incidence, which accords with the statistics for HFRS cases in 2014–2015. The spatial heterogeneity of HFRS disease may be influenced by rodent community composition, which is associated with local environmental conditions. Therefore, future work should focus on preventing HFRS is moist, warm environments. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by hantaviruses. Landscape can influence the risk of hantavirus infection for humans, mainly through its effect on rodent community composition and distribution. It is important to understand how landscapes influence population dynamics for different rodent species and the subsequent effect on HFRS risk.Methods: To determine how rodent community composition influenced human hantavirus infection, we monitored rodent communities in the prefecture-level cities of Loudi and Shaoyang, China, from 2006 to 2013. Land use data were extracted from satellite images and rodent community diversity was analyzed in 45 trapping sites, in different environments. Potential contact matrices, determining how rodent community composition influence HFRS infection among different land use types, were estimated based on rodent community composition and environment type for geo-located HFRS cases.Results: Apodemus agrarius and Rattus norvegicus were the predominant species in Loudi and Shaoyang, respectively. The major risk of HFRS infection was concentrated in areas with cultivated land and was associated with A. agrarius, R. norvegicus, and Rattus flavipectus. In urban areas in Shaoyang, Mus musculus was related to risk of hantavirus infection.Conclusions: Landscape features and rodent community dynamics may affect the risk of human hantavirus infection. Results of this study may be useful for the development of HFRS prevention initiatives that are customized for regions with different geographical environments. [ABSTRACT FROM AUTHOR]

Background: Hand, foot and mouth disease (HFMD) is one of the highest reported infectious diseases with several outbreaks across the world. This study aimed at describing epidemiological characteristics, investigating spatio-temporal clustering changes, and identifying determinant factors in different clustering areas of HFMD.Methods: Descriptive statistics was used to evaluate the epidemic characteristics of HFMD from 2009 to 2015. Spatial autocorrelation and spatio-temporal cluster analysis were used to explore the spatial temporal patterns. An autologistic regression model was employed to explore determinants of HFMD clustering.Results: The incidence rates of HFMD ranged from 54.31/10 million to 318.06/10 million between 2009 and 2015 in Hunan. Cases were mainly prevalent in children aged 5 years and even younger, with an average male-to-female sex ratio of 1.66, and two epidemic periods in each year. Clustering areas gathered in the northern regions in 2009 and in the central regions from 2010 to 2012. They moved to central-southern regions in 2013 and 2014 and central-western regions in 2015. The significant risk factors of HFMD clusters were rainfall (OR = 2.187), temperature (OR = 4.329) and humidity (OR = 2.070). The protect factor was wind speed (OR = 0.258).Conclusions: The HFMD incidence from 2009 to 2015 in Hunan showed a new spatiotemporal clustering tendency, with the shifting trend of clustering areas toward south and west. Meteorological factors showed a strong association with HFMD clustering, which may assist in predicting future spatial-temporal clusters. [ABSTRACT FROM AUTHOR]

H9N2 avian influenza viruses (AIVs) are highly prevalent and of low pathogenicity in domestic poultry. These viruses show a high genetic compatibility with other subtypes of AIVs and have been involved in the genesis of H5N1, H7N9 and H10N8 viruses causing severe infection in humans. The first case of human infection with H9N2 viruses in Hunan province of China have been confirmed in November 2013 and identified that H9N2 viruses from live poultry markets (LPMs) near the patient’s house could be the source of infection. However, the prevalence, distribution and genetic characteristics of H9N2 viruses in LPMs all over the province are not clear. We collected and tested 3943 environmental samples from 380 LPMs covering all 122 counties/districts of Hunan province from February to April, 2014. A total of 618 (15.7%) samples were H9 subtype positive and 200 (52.6%) markets in 98 (80.3%) counties/districts were contaminated with H9 subtype AIVs. We sequenced the entire coding sequences of the genomes of eleven H9N2 isolates from environmental samples. Phylogenetic analysis showed that the gene sequences of the H9N2 AIVs exhibited high homology (94.3%-100%). All eleven viruses were in a same branch in the phylogenetic trees and belonged to a same genotype. No gene reassortment had been found. Molecular analysis demonstrated that all the viruses had typical molecular characteristics of contemporary avian H9N2 influenza viruses. Continued surveillance of AIVs in LPMs is warranted for identification of further viral evolution and novel reassortants with pandemic potential. [ABSTRACT FROM AUTHOR]