Decoding and reconstructing disease relations between dry eye and depression: a multimodal investigation comprising meta-analysis, genetic pathways and Mendelian randomization.

INTRODUCTION: The clinical presentations of dry eye disease (DED) and depression (DEP) often comanifest. However, the robustness and the mechanisms underlying this association were undetermined. OBJECTIVES: To this end, we set up a three-segment study that employed multimodality results (meta-analysis, genome-wide association study [GWAS] and Mendelian randomization [MR]) to elucidate the association, common pathways and causality between DED and DEP. METHODS: A meta-analysis comprising 26 case-control studies was first conducted to confirm the DED-DEP association. Next, we performed a linkage disequilibrium (LD)-adjusted GWAS and targeted phenotype association study (PheWAS) in East Asian TW Biobank (TWB) and European UK Biobank (UKB) populations. Single-nucleotide polymorphisms (SNPs) were further screened for molecular interactions and common pathways at the functional gene level. To further elucidate the activated pathways in DED and DEP, a systemic transcriptome review was conducted on RNA sequencing samples from the Gene Expression Omnibus. Finally, 48 MR experiments were implemented to examine the bidirectional causation between DED and DEP. RESULTS: Our meta-analysis showed that DED patients are associated with an increased DEP prevalence (OR = 1.83), while DEP patients have a concurrent higher risk of DED (OR = 2.34). Notably, cross-disease GWAS analysis revealed that similar genetic architecture (rG = 0.19) and pleiotropic functional genes contributed to phenotypes in both diseases. Through protein-protein interaction and ontology convergence, we summarized the pleiotropic functional genes under the ontology of immune activation, which was further validated by a transcriptome systemic review. Importantly, the inverse variance-weighted (IVW)-MR experiments in both TWB and UKB populations (p value <0.001) supported the bidirectional exposure-outcome causation for DED-to-DEP and DEP-to-DED. Despite stringent LD-corrected instrumental variable re-selection, the bidirectional causation between DED and DEP remained. CONCLUSION: With the multi-modal evidence combined, we consolidated the association and causation between DED and DEP.

[Response of Soil Microbial Diversity to Long-term Enclosure in Degraded Patches of Alpine Meadow in the Source Zone of the Yellow River].

The soil pH, water content, nutrients, and microbial community composition and diversity among one-year term (E1), short-term (E4), and long-term (E10) enclosures were analyzed for understanding the response of soil bacterial and fungal communities to long-term enclosure in degraded patches of alpine meadow in the source zone of the Yellow River, through determining the soil physicochemical properties and microbial diversity using high-throughput sequencing technology. The results showed that the E1 enclosure significantly decreased soil pH, whereas long-term and short-term enclosures increased soil pH. The long-term enclosure could significantly increase soil water content and total nitrogen content, and the short-term enclosure could significantly increase available phosphorus content. The long-term enclosure could significantly increase the bacterial Proteobacteria. The short-term enclosure could significantly increase the abundance of the bacteria Acidobacteriota. However, the abundance of the fungus Basidiomycota decreased in both long-term and short-term enclosures. With the extension of enclosure years, the Chao1 index and Shannon diversity index of bacteria showed an increasing trend, but there was no significant difference between long-term and short-term enclosures. The Chao1 index of fungi gradually increased, and the Shannon diversity index first increased and then decreased, but there was no significant difference between long-term and short-term enclosures. Redundancy analysis indicated that enclosure altered microbial community composition and structure mainly by changing soil pH and water content. Therefore, the E4 short-term enclosure could significantly improve the soil physicochemical properties and microbial diversity at the degraded patches of alpine meadow. The long-term enclosure is not necessary and will lead to the waste of grassland resources, reduction in biodiversity, and restriction of wildlife activities.

[Effect of Nitrogen Addition on Soil Fungal Diversity in a Degraded Alpine Meadow at Different Slopes].

This study proposed nitrogen addition experiments to analyze the effects of exogenous nitrogen addition on soil fungal diversity in alpine meadow. All the experiments were performed in degraded alpine meadow with two different slopes (gentle slope and steep slope) in Guoluo Prefecture of the Sanjiangyuan Region, and the sequence and analysis of ITS of soil fungi were performed using MiSeq PE250 sequencing technology. Comparative analysis was carried out with three nitrogen addition levels on soil fungal diversity in degraded grassland with different slopes, which included low nitrogen (LN, 2 g·m-2), middle nitrogen (MN, 5 g·m-2), and high nitrogen (HN, 10 g·m-2). The results showed that:① the distribution groups of fungi in the soil were Ascomycota, Basidiomycota, Mortierellomycota, and Glomomycota, and the dominant bacteria was Ascomycota. ② The dominant genera were Mortierella and Archaeorhizomyces, and there were no differences in response to different slopes and nitrogen addition levels. ③ A total of 95 genera (Gibberellum, Preussia, etc.) were identified and significantly differed between two different slopes (P<0.05). ④ Bacteria with a relative abundance less than 1% had significant differences in nitrogen addition at different levels on the same slope (P<0.05). 5 In addition, the analyses of α and ß diversities showed that soil fungal community structure was stable under different slopes and nitrogen addition levels. Exogenous nitrogen supplementation significantly improved the relative abundance of non-dominant fungal communities without destroying soil fungal community structure.

[Changes in Soil Bacterial Community Diversity in Degraded Patches of Alpine Meadow in the Source Area of the Yellow River].

MiSeq sequencing technology was used to investigate the bacterial compositions and diversities of active patch, non-active patch, recovered patch, and healthy alpine meadows so as to understand the changes in soil bacterial community diversity during altitude change and alpine meadow degradation. The relationship between bacterial diversity and environmental factors was analyzed using redundancy analysis (RDA). The results showed that the dominant bacterial phyla in the soil included Proteobacteria, Actinobacteriota, and Acidobacteriota in the study areas. The dominant bacterial genera that were identified via the MiSeq were RB41, Sphingomonas, and Bradyrhizobium. The relative abundance of these genera decreased with altitude increase and increased with the restoration progress of degraded patches but was significantly lower than that in the alpine meadow (P<0.05). The abundance of functional bacteria related to carbon fixation in degraded patches was higher than that in the healthy alpine meadow. The bacterial Chao1 index and species number in different types of degraded patches were significantly higher than those in the alpine meadow (P<0.05). The results of the RDA suggest that biological soil crust coverage and total nitrogen were the main influencing factors on dominant bacterial phyla at the altitude of 4013 m. Biomass, total nitrogen, and pH had a great influence on the dominant bacterial phyla at the altitude of 4224 m. Biomass and total potassium significantly affected the distribution of bacterial genera at the altitude of 4013 m. Sedge coverage and available nitrogen were the main influencing factors on bacterial dominant genera at the altitude of 4224 m. Biological soil crusts and pH had a great influence on bacterial diversities. The bacterial influence factors varied greatly at different altitude areas. Therefore, we should not only pay attention to the effect of alpine meadow degradation but also consider the effect of altitude in the study of bacterial diversity changes.

Genetics behind Cerebral Disease with Ocular Comorbidity: Finding Parallels between the Brain and Eye Molecular Pathology.

Cerebral visual impairments (CVIs) is an umbrella term that categorizes miscellaneous visual defects with parallel genetic brain disorders. While the manifestations of CVIs are diverse and ambiguous, molecular diagnostics stand out as a powerful approach for understanding pathomechanisms in CVIs. Nevertheless, the characterization of CVI disease cohorts has been fragmented and lacks integration. By revisiting the genome-wide and phenome-wide association studies (GWAS and PheWAS), we clustered a handful of renowned CVIs into five ontology groups, namely ciliopathies (Joubert syndrome, Bardet-Biedl syndrome, Alstrom syndrome), demyelination diseases (multiple sclerosis, Alexander disease, Pelizaeus-Merzbacher disease), transcriptional deregulation diseases (Mowat-Wilson disease, Pitt-Hopkins disease, Rett syndrome, Cockayne syndrome, X-linked alpha-thalassaemia mental retardation), compromised peroxisome disorders (Zellweger spectrum disorder, Refsum disease), and channelopathies (neuromyelitis optica spectrum disorder), and reviewed several mutation hotspots currently found to be associated with the CVIs. Moreover, we discussed the common manifestations in the brain and the eye, and collated animal study findings to discuss plausible gene editing strategies for future CVI correction.

[Responses of Different Degradation Stages of Alpine Wetland on Soil Microbial Community in the Yellow River Source Zone].

MiSeq sequencing technology was used to analyze the microbial community diversity of soil in alpine wetlands to understand the degradation processes and environmental factors in these areas. The results showed that the severity of soil degradation changed the species diversity of soil microorganisms at the level of OTUs, and grass patches contained more species than frozen-thawing patches. The soil fungi species of OTUs changed significantly. The diversity indexes of bacteria (between the frozen-thawing patches and the grass patches) were higher than that of fungi. The dominant microbial species were consistent among different degradation stages. The dominant species of bacteria and fungi were Proteobacteria and RB41, and Ascomycota and Mortierella, respectively. The abundance of dominant microorganisms was significantly between un-degraded and heavily degraded areas, except for RB41 (P<0.05). The dominant microorganisms in the grass patches were more sensitive than those in the frozen-thawing patches. It was found that the main factors affecting the microbial community structure of soil were water content, organic carbon, microbial biomass carbon, microbial biomass nitrogen, and sedge coverage. Microbial diversity may decrease in heavily degraded alpine wetlands. Thus, the frozen-thawing patches and sedge species should be first protected, and the supplements of soil water content, soil organic carbon, microbial biomass carbon, and nitrogen should be strengthened for alpine wetland restoration.

Urban-rural differences in the prevalence and correlates of mild cognitive impairment in community-dwelling older adults in Taiwan: The EMCIT study.

BACKGROUND: Taiwan is a rapidly aging society. The elderly with mild cognitive impairment (MCI) have increased risk of dementia, and this is a population-based report using standard neuropsychological tests and expert consensus diagnosis to assess the MCI prevalence and its associated factors in Taiwan. METHOD: The Epidemiology of Mild Cognitive Impairment study in Taiwan (EMCIT) is a community-based, prospective cohort study. Independently-living individuals aged ≧60 years in a rural area (n = 122) and in an urban area (n = 348) of New Taipei City, Taiwan, completed detailed neuropsychological tests at the cohort baseline. Diagnosis of MCI was ascertained through expert consensus based on 2011 NIA-AA criteria. RESULTS: Of 470 participants recruited between 2017 and 2019 (mean age 71.2 ± 5.4 years), the prevalence of MCI was higher in the rural area than in the urban area (25.1% vs. 10.8%, p < 0.001) after standardized for age, gender, and level of education. Having lower education and having depression symptoms were consistently associated with increased risk of MCI in both urban and rural areas (p < 0.05). Being male and diabetes were additionally associated with MCI prevalence in urban areas. CONCLUSION: In this community-based prospective cohort study in Taiwan, the prevalence of MCI in the rural community was much higher than that in the urban community. Different strategies may be needed to targeted different types of communities.

[Study on low temperature moisture regain drying characteristics of different grades of Angelicae Sinensis Radix based on Weibull distribution function].

The drying process of different grades of Angelicae Sinensis Radix under low temperature and resurgence conditions was simulated based on the Weibull distribution function,in order to clarify the low-temperature moisture regain drying characteristics of different grades of Angelicae Sinensis Radix,and explore the effect of grade and drying conditions on the drying process of Angelicae Sinensis Radix. Research results indicated that the Weibull function can be used to simulate different grades of Angelicae Sinensis Radix low-temperature moisture regain drying process,and the lower the drying temperature,the smaller the grade,and the better the simulation effect. The grade and drying temperature showed a significant effect on the low-temperature moisture regain drying process of Angelicae Sinensis Radix,and the effect of temperature on the relative moisture regain rate of Angelicae Sinensis Radix was greater than the grade. The relative moisture regain rate of different grades of Angelicae Sinensis Radix at 40 ℃ was higher than 55 ℃,and the relative moisture regain rate at 40 ℃ was first class > second class > third class. After drying,the moisture ratio at 40 ℃ was lower than that at 55 ℃; the effect of the grade on the effective diffusion coefficient of dry water was greater than the temperature. Under different conditions of 40 ℃ and 55 ℃ moisture regain,the effective diffusion coefficient of water was between 2. 941 6×10-6-7. 991 5×10-6 and3. 093 8×10-6-8. 483 8×10-6 for different grades. Under the same temperature conditions,the effective diffusion coefficient of water was first class > second class > third class. Therefore,Weibull function can be used to study and simulate the drying characteristics of different grades of Angelicae Sinensis Radix under low-temperature moisture regain conditions,providing experimental basis for the improvement of traditional drying technology of Angelicae Sinensis Radix and the optimization of drying process of different specifications or grades of Angelicae Sinensis Radix.

[Study on history of processing and drying of Angelicae sinensis].

Angelicae sinensis Radix( ASR) is a commonly used medicinal material in Chinese medicine,widely used in clinical practice of Chinese medicine,Gansu province is the genuine production area of ASR. This paper studies the evolution law of drying method of ASR,the results showed that drying process was the key affection of the medicinal properties and quality of ASR,and it was an important reflection of the authentic properties of ASR. The drying history of ASR has gradually changed from the earliest shade drying to various drying methods. The Chinese Pharmacopoeia stipulates that the drying method of ASR is"fumigation drying",and the traditional drying method can not meet the processing needs of the origin. In recent years,the new drying methods and drying effects on the quality of ASR are more.

ATP-Binding Cassette Transporter VcaM from Vibrio cholerae is Dependent on the Outer Membrane Factor Family for Its Function.

Vibrio cholerae ATP-binding cassette transporter VcaM (V. cholerae ABC multidrug resistance pump) has previously been shown to confer resistance to a variety of medically important drugs. In this study, we set to analyse its properties both in vitro in detergent-solubilised state and in vivo to differentiate its dependency on auxiliary proteins for its function. We report the first detailed kinetic parameters of purified VcaM and the rate of phosphate (Pi) production. To determine the possible functional dependencies of VcaM on the tripartite efflux pumps we then utilized different E. coli strains lacking the principal secondary transporter AcrB (Acriflavine resistance protein), as well as cells lacking the outer membrane factor (OMF) TolC (Tolerance to colicins). Consistent with the ATPase function of VcaM we found it to be susceptible to sodium orthovanadate (NaOV), however, we also found a clear dependency of VcaM function on TolC. Inhibitors targeting secondary active transporters had no effects on either VcaM-conferred resistance or Hoechst 33342 accumulation, suggesting that VcaM might be capable of engaging with the TolC-channel without periplasmic mediation by additional transporters. Our findings are indicative of VcaM being capable of a one-step substrate translocation from cytosol to extracellular space utilising the TolC-channel, making it the only multidrug ABC-transporter outside of the MacB-family with demonstrable TolC-dependency.

[Analysis Characteristics of Inorganic Elements in Different Organs of Hedysarum polybotrys in Different Growing Variation].

Objective: To study the characteristics of inorganic elements in different organs of Hedysarum polybotrys in different growing variation, including root, rhizome, leaf, flower and fruit. Methods: The content of 13 inorganic elements in different organs were detected by using flame atomic absorption method, and then the characteristics of inorganic elements in different organs of Hedysarum polybotrys in different growing variation were analyzed. Results: There were abundant inorganic elements in root, rhizome, leaf, flower and fruit, the change in the contents of inorganic elements at different growing variation related to the season. The contents of Fe,Cu,Ca,Mn,Zn, Mg, Cr, Co, Na, Li,Ni and K were regularly changed with the change of growing variation, and Cd was not deteced. The content of Cu and Ca order was leaf > root > rhizome, and the content of Mn at leaf was higher than that at other organs during June to October. Conclusion: The results provide scientific basis for the harvest time of Hedysari Radix and the development of non-medicinal portions.

Spatiotemporal Clustering Analysis and Risk Assessments of Human Cutaneous Anthrax in China, 2005-2012.

OBJECTIVE: To investigate the epidemic characteristics of human cutaneous anthrax (CA) in China, detect the spatiotemporal clusters at the county level for preemptive public health interventions, and evaluate the differences in the epidemiological characteristics within and outside clusters. METHODS: CA cases reported during 2005-2012 from the national surveillance system were evaluated at the county level using space-time scan statistic. Comparative analysis of the epidemic characteristics within and outside identified clusters was performed using using the χ2 test or Kruskal-Wallis test. RESULTS: The group of 30-39 years had the highest incidence of CA, and the fatality rate increased with age, with persons ≥70 years showing a fatality rate of 4.04%. Seasonality analysis showed that most of CA cases occurred between May/June and September/October of each year. The primary spatiotemporal cluster contained 19 counties from June 2006 to May 2010, and it was mainly located straddling the borders of Sichuan, Gansu, and Qinghai provinces. In these high-risk areas, CA cases were predominantly found among younger, local, males, shepherds, who were living on agriculture and stockbreeding and characterized with high morbidity, low mortality and a shorter period from illness onset to diagnosis. CONCLUSION: CA was geographically and persistently clustered in the Southwestern China during 2005-2012, with notable differences in the epidemic characteristics within and outside spatiotemporal clusters; this demonstrates the necessity for CA interventions such as enhanced surveillance, health education, mandatory and standard decontamination or disinfection procedures to be geographically targeted to the areas identified in this study.

Spatiotemporal transmission dynamics of hemorrhagic fever with renal syndrome in China, 2005-2012.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by many serotypes of hantaviruses. In China, HFRS has been recognized as a severe public health problem with 90% of the total reported cases in the world. This study describes the spatiotemporal dynamics of HFRS cases in China and identifies the regions, time, and populations at highest risk, which could help the planning and implementation of key preventative measures. METHODS: Data on all reported HFRS cases at the county level from January 2005 to December 2012 were collected from Chinese Center for Disease Control and Prevention. Geographic Information System-based spatiotemporal analyses including Local Indicators of Spatial Association and Kulldorff's space-time scan statistic were performed to detect local high-risk space-time clusters of HFRS in China. In addition, cases from high-risk and low-risk counties were compared to identify significant demographic differences. RESULTS: A total of 100,868 cases were reported during 2005-2012 in mainland China. There were significant variations in the spatiotemporal dynamics of HFRS. HFRS cases occurred most frequently in June, November, and December. There was a significant positive spatial autocorrelation of HFRS incidence during the study periods, with Moran's I values ranging from 0.46 to 0.56 (P<0.05). Several distinct HFRS cluster areas were identified, mainly concentrated in northeastern, central, and eastern of China. Compared with cases from low-risk areas, a higher proportion of cases were younger, non-farmer, and floating residents in high-risk counties. CONCLUSIONS: This study identified significant space-time clusters of HFRS in China during 2005-2012 indicating that preventative strategies for HFRS should be particularly focused on the northeastern, central, and eastern of China to achieve the most cost-effective outcomes.

Association between hemorrhagic fever with renal syndrome epidemic and climate factors in Heilongjiang Province, China.

The purpose of this study was to quantify the relationship between climate variation and transmission of hemorrhagic fever with renal syndrome (HFRS) in Heilongjiang Province, a highly endemic area for HFRS in China. Monthly notified HFRS cases and climatic data for 2001-2009 in Heilongjiang Province were collected. Using a seasonal autoregressive integrated moving average model, we found that relative humidity with a one-month lag (ß = -0.010, P = 0.003) and a three-month lag (ß = 0.008, P = 0.003), maximum temperature with a two-month lag (ß = 0.082, P = 0.028), and southern oscillation index with a two-month lag (ß = -0.048, P = 0.019) were significantly associated with HFRS transmission. Our study also showed that predicted values expected under the seasonal autoregressive integrated moving average model were highly consistent with observed values (Adjusted R(2) = 83%, root mean squared error = 108). Thus, findings may help add to the knowledge gap of the role of climate factors in HFRS transmission in China and also assist national local health authorities in the development/refinement of a better strategy to prevent HFRS transmission.

Spatiotemporal patterns of Japanese encephalitis in China, 2002-2010.

OBJECTIVE: The aim of the study is to examine the spatiotemporal pattern of Japanese Encephalitis (JE) in mainland China during 2002-2010. Specific objectives of the study were to quantify the temporal variation in incidence of JE cases, to determine if clustering of JE cases exists, to detect high risk spatiotemporal clusters of JE cases and to provide evidence-based preventive suggestions to relevant stakeholders. METHODS: Monthly JE cases at the county level in mainland China during 2002-2010 were obtained from the China Information System for Diseases Control and Prevention (CISDCP). For the purpose of the analysis, JE case counts for nine years were aggregated into four temporal periods (2002; 2003-2005; 2006; and 2007-2010). Local Indicators of Spatial Association and spatial scan statistics were performed to detect and evaluate local high risk space-time clusters. RESULTS: JE incidence showed a decreasing trend from 2002 to 2005 but peaked in 2006, then fluctuated over the study period. Spatial cluster analysis detected high value clusters, mainly located in Southwestern China. Similarly, we identified a primary spatiotemporal cluster of JE in Southwestern China between July and August, with the geographical range of JE transmission increasing over the past years. CONCLUSION: JE in China is geographically clustered and its spatial extent dynamically changed during the last nine years in mainland China. This indicates that risk factors for JE infection are likely to be spatially heterogeneous. The results may assist national and local health authorities in the development/refinement of a better preventive strategy and increase the effectiveness of public health interventions against JE transmission.

Word form encoding in Chinese word naming and word typing.

The process of word form encoding was investigated in primed word naming and word typing with Chinese monosyllabic words. The target words shared or did not share the onset consonants with the prime words. The stimulus onset asynchrony (SOA) was 100ms or 300ms. Typing required the participants to enter the phonetic letters of the target word, which correspond roughly to the onset and the rhyme of the word's syllable. Regardless of SOAs, response times were shorter in the related condition than in the unrelated condition (an onset priming effect) for word typing, but were similar for word naming. The results suggest that naming and typing in Chinese may involve somewhat different word form encoding processes (syllable driven in naming, but segment driven in typing) even though both tasks require accessing the phonological codes. It appears, then, that the kind of outputs a production system is designed to produce can flexibly and adaptively alter the way the system is organized and operates.

Quarantine methods and prevention of secondary outbreak of pandemic (H1N1) 2009.

During the 2009 influenza (H1N1) pandemic, some countries used quarantine for containment or mitigation. Of 152 quarantined university students we studied, risk for illness was higher for students quarantined in a room with a person with a confirmed case; we found no difference between students quarantined in double or single rooms.

[Spatial epidemiological study on malaria epidemics in Hainan province].

OBJECTIVE: To better understand the characteristics of spatial distribution of malaria epidemics in Hainan province and to explore the relationship between malaria epidemics and environmental factors, as well to develop prediction model on malaria epidemics. METHODS: Data on Malaria and meteorological factors were collected in all 19 counties in Hainan province from May to Oct., 2000, and the proportion of land use types of these counties in this period were extracted from digital map of land use in Hainan province. Land surface temperatures (LST) were extracted from MODIS images and elevations of these counties were extracted from DEM of Hainan province. The coefficients of correlation of malaria incidences and these environmental factors were then calculated with SPSS 13.0, and negative binomial regression analysis were done using SAS 9.0. RESULTS: The incidence of malaria showed (1) positive correlations to elevation, proportion of forest land area and grassland area; (2) negative correlations to the proportion of cultivated area, urban and rural residents and to industrial enterprise area, LST; (3) no correlations to meteorological factors, proportion of water area, and unemployed land area. The prediction model of malaria which came from negative binomial regression analysis was: I (monthly, unit: 1/1,000,000) = exp (-1.672-0.399xLST). CONCLUSION: Spatial distribution of malaria epidemics was associated with some environmental factors, and prediction model of malaria epidemic could be developed with indexes which extracted from satellite remote sensing images.