Detrended seasonal relationships and impact of climatic factors combined with spatiotemporal effect on the prevalence of human brucellosis.

Human brucellosis (HB) is a seasonal and climate-affected infectious disease that is posing an increasing threat to public health and economy. However, most of the research on the seasonal relationships and impact of climatic factors on HB did not consider the secular trend and spatiotemporal effect related to the disease. We herein utilized long-term surveillance data on HB from 2008 to 2020 using sinusoidal models to explore detrended relationships between climatic factors and HB. In addition, we assessed the impact of such climatic factors on HB using a spatial panel data model combined with the spatiotemporal effect. HB peaked around mid-May. HB was significantly correlated with climatic factors with 1-5-month lag when the respective correlations reached the maximum across the different lag periods. Each 0.1 °C increase in temperature led to 0.5% decrease in the 5-month lag incidence of HB. We also observed a positive spatiotemporal effect on the disease. Our study provides a detailed and in-depth overview of seasonal relationships and impact of climatic factors on HB. In addition, it proposes a novel approach for exploring the seasonal relationships and quantifying the impacts of climatic factors on various infectious diseases.

Seroprevalence trend of human brucellosis and MLVA genotyping characteristics of Brucella melitensis in Shaanxi Province, China, during 2008-2020.

In this study, a total of 179,907 blood samples from populations with suspected Brucella spp. infections were collected between 2008 and 2020 and analyzed by the Rose Bengal plate test (RBPT) and serum agglutination test (SAT). Moreover, conventional biotyping, B. abortus-melitensis-ovis-suis polymerase chain reaction (AMOS-PCR), and multiple-locus variable-number tandem repeat analysis (MLVA) was applied to characterize the isolated strains. A total of 8103 (4.50%) samples were positive in RBPT, while 7705 (4.28%, 95% confidence interval (CI) 4.19-4.37) samples were positive in SAT. There was a significant difference in seroprevalence for human brucellosis over time, in different areas and different cities (districts) (χ2 = 2 = 32.23, 1984.14, and 3749.51, p < .05). The highest seropositivity (8.22% (4, 965/60393; 95% CI 8.00-8.44) was observed in Yulin City, which borders Inner Mongolia, Ningxia, and Gansu Province, China, regions that have a high incidence of human brucellosis. Moreover, 174 Brucella strains were obtained, including nine with B. melitensis bv. 1, 145 with B. melitensis bv. 3, and 20 with B. melitensis variants. After random selection, 132 B. melitensis were further genotyped using MLVA-16. The 132 strains were sorted into 100 MLVA-16 genotypes (GTs) (GT 1-100), 81 of which were single GTs represented by singular independent strains. The remaining 19 shared GTs involved 51 strains, and each GT included two to seven isolates from the Shaan northern and Guanzhong areas. These data indicated that although sporadic cases were a dominant epidemic characteristic of human brucellosis in this province, more than 38.6% (51/132) outbreaks were also found in the Shaan northern area and Guanzhong areas. The 47 shared MLVA-16 GTs were observed in strains (n = 71) from this study and strains (n = 337) from 19 other provinces of China. These data suggest that strains from the northern provinces are a potential source of human brucellosis cases in Shaanxi Province. It is urgent to strengthen the surveillance and control of the trade and transfer of infected sheep among regions.

Exploring risk transfer of human brucellosis in the context of livestock agriculture transition: A case study in Shaanxi, China.

With the booming of worldwide agriculture intensification, brucellosis, one of the most neglected zoonotic diseases, has become an increasing challenge for global public health. Although the transmission patterns of human brucellosis (HB) have been studied in many regions, the dynamic transfer processes of risk and its driving factors remain poorly understood, especially in the context of agricultural intensification. This study attempted to explore the risk transfer of HB between the exact epidemic areas and the neighboring or distant low-risk areas to explain the impact of livestock agriculture intensification and foodborne infections on the transmission of HB in Shaanxi Province as a case study. We adopted multiple approaches, including test-based methods, model-based methods, and a geographical detector to detect the spatial-temporal dynamic changes of high-risk epidemic areas of HB at the county scale. We also quantitatively estimated how the related factors drove the risk transfer of the disease. Results confirmed the risk transfer pattern of HB with an expansion from north to south in Shaanxi Province and identified two primary transfer routes. In particular, in the traditional epidemic areas of the Shaanbei plateau, the farm agglomeration effect can significantly increase the risk of HB. Meanwhile, retail outlets for milk and dairy products were partially responsible for the foodborne infections of HB in the emerging epidemic areas of Xi'an. This study not only contributed helpful insights to support HB control and prevention in the rapid transition of livestock agriculture but also provided possible directions for further research on foodborne HB infections in urbanized areas.

Changes in the epidemiological characteristics of human brucellosis in Shaanxi Province from 2008 to 2020.

In the present study, surveys of case numbers, constituent ratios, conventional biotyping, and multilocus sequence typing (MLST) were applied to characterize the incidence rate and epidemiological characteristics of human brucellosis in Shaanxi Province, China. A total of 12,215 human brucellosis cases were reported during 2008-2020, for an annual average incidence rate of 2.48/100,000. The most significant change was that the county numbers of reported cases increased from 36 in 2008 to 84 in 2020, with a geographic expansion trend from northern Shaanxi to Guanzhong, and southern Shaanxi regions; the incidence rate declined in previous epidemic northern Shaanxi regions while increasing each year in Guanzhong and southern Shaanxi regions such as Hancheng and Xianyang. The increased incidence was closely related to the development of large-scale small ruminants (goats and sheep) farms in Guanzhong and some southern Shaanxi regions. Another significant feature was that student cases (n = 261) were ranked second among all occupations, accounting for 2.14% of the total number of cases, with the majority due to drinking unsterilized goat milk. Three Brucella species were detected (B. melitensis (bv. 1, 2, 3 and variant), B. abortus bv. 3/6, and B. suis bv. 1) and were mainly distributed in the northern Shaanxi and Guanzhong regions. Three known STs (ST8, ST2, and ST14) were identified based on MLST analysis. The characteristics that had not changed were that B. melitensis strains belonging to the ST8 population were the dominant species and were observed in all nine regions during the examined periods. Strengthened human and animal brucellosis surveillance and restriction of the transfer of infected sheep (goats) as well as students avoiding drinking raw milk are suggested as optimal control strategies.

Molecular characterization of gut microbial shift in SD rats after death for 30 days.

To observe the temporal shifts of the intestinal microbial community structure and diversity in rats for 30 days after death. Rectal swabs were collected from rats before death (BD) and on day 1, 5, 10, 15, 20, 25, and 30 after death (AD). Bacteria genomic DNA was extracted and V3 + V4 regions of 16S rRNA gene were amplified by PCR. The amplicons were sequenced at Illumina MiSeq sequencing platform. The bacterial diversity and richness showed similar results from day 1 to 5 and day 10 to 25 all presenting downtrend, while from day 5 to 10 showed slightly increased. The relative abundance of Firmicutes and Proteobacteria displayed inverse variation in day 1, 5, 10 and that was the former decreased, the latter increased. Bacteroidetes, Spirochaete and TM7 in day 15, 20, 25, 30 was significantly decline comparing with BD. Enterococcus and Proteus displayed reduced trend over day 1, 5, 10 and day 10, 15, 20, 25, respectively, while Sporosarcina showed obvious elevation during day 15, 20, 25. Accordingly, there was a certain correlation between intestinal flora succession and the time of death. The results suggested that intestinal flora may be potential indicator to aid estimation of post-mortem interval (PMI).

Brucellosis Outbreak Caused by Brucella melitensis - Jingyang County, Shaanxi Province, China, March-May, 2020.

What is already known about this topic? Brucellosis is one of the world's most overlooked zoonotic diseases, and humans can easily acquire brucellosis from animals and their products. Reemerging brucellosis outbreaks are probably attributable to sociocultural factors and compounded by the lack of adequate control measures in sheep and goat rearing systems. What is added by this report? This is the first identified outbreak caused by Brucella melitensisbv.3 in Jingyang County, Xianyang City, Shaanxi Province. A total of 13 seropositve cases (7 acute patients and 6 asymptomatic persons) were identified from March to May, 2020, and the investigation indicated that sheep-to-canine-to-human was the likely transmission route. What are the implications for public health practice? Effective control of sheep brucellosis will significantly reduce the risk of human brucellosis. Priority should be given to building cooperation between all stakeholders, maintaining epidemiological surveillance to detect human brucellosis at medical centers, and making case reporting mandatory for both veterinary and public health services.

The influence of gut microbiota dysbiosis to the efficacy of 5-Fluorouracil treatment on colorectal cancer.

Colorectal cancer is one of the most frequently diagnosed cancers worldwide. Gut flora can modulate the host response to chemotherapeutic drugs. However, the understanding regarding the relationship between the gut microbiota and the antitumor efficacy of 5- Fluorouracil (5-FU) treatment is limited. Therefore, we compared the tumor size and profiled the gut microbiota of mice treated with 5-FU, combined with probiotics or ABX (an antibiotic cocktail of antibiotics) by using the Colorectal Cancer (CRC) mouse model and high-throughput sequencing. The results elucidated that ABX administration diminished the antitumor efficacy of 5-FU in mice and supplementation of probiotics upon 5-FU treatment could not significantly increase the efficacy of 5-FU treatment, despite improving mice body weight at day 33. There were significant differences in fecal bacteria community among the four groups (ANOSIM p < 0.05). ABX administration reduced microbiota biodiversity and altered microbiota community. The pathogenic bacteria included Escherichia shigella and Enterobacter significantly increased, while other commensal bacterial decreased unidentified Firmicutes increased and the opportunistic pathogens decreased after the administration of Probiotics. In addition, 5-FU treatment also changed the diversity and the community composition of the gut mirobiota. The relative abundance of genus Lachnospiracea_NK4 A136, Bacteroides, Odoribacter, Mucispirillum, and Blautia were significantly increased compared to the control group. Additionally, functional capacity analysis of gut microbiota using PICRUSt showed that genes involved in amino acid metabolism, replication and repair translation, nucleotide metabolism expressed much lower in FU.ABX group than the other groups. The current results suggest that ABX administration disrupted the gut microbiota in mice, which contributed to the reduction of antitumor efficacy of 5-FU.

[Identification on host animals for plague by DNA barcoding technology in Shaanxi province].

OBJECTIVE: To apply the DNA barcoding technology for identification on host animal and to establish the host animal DNA bar code database on natural foci of plague in Shaanxi. METHODS: 139 host animals belonging to 3 orders, 6 families and 12 genera and 62 residues belonging to 7 species from 8 different parts of the province, were detected. DNA barcoding technology was used to analyze the DNA CO I gene sequence on the natural foci of plague in Dingbian county. RESULTS: The intra-specific genetic distance was less than 2% while the inter-specific distance ranged from 8.9% to 15.1%. Fourteen major clusters were apparently showed on a Neighbor-Joining tree. Residue samples could be detected regarding the objective gene. Alashan ground squirrel was previously noticed to carry 14 major clusters, which were previously mistakenly named as Citellus dauricus in Dingbian county. CONCLUSION: DNA barcoding technology could overcome the shortcomings caused by the morphological identification so could be used to identify the host animal and residues in the natural focus of plague.

[Effect of adjuvant therapy with Dingguier umbilical paste on intestinal flora of diarrhea infants and its action characteristics].

The applicator therapy is a unique method to treat infant diarrhea in traditional Chinese medicines and widely applied in clinical practice. Currently, many researchers have proved the rationality of the therapy based on the traditional Chinese medicine mechanism and on the data from clinical practice, but its action mechanism is uncertain at present. In this study, with the assistance of pediatric practitioners, the automated ribosomal intergenic-spacer analysis (ARISA) was adopted to study the effect of the adjuvant therapy with Dingguier umbilical paste on intestinal flora of diarrhea infants, in which Dingguier umbilical paste served as the adjuvant therapy in oral traditional Chinese medicines and fecal samples of infants with different diarrhea symptoms were collected and used as the study materials. The results showed that the adjuvant therapy had a significant effect on the shift of intestinal flora, which was associated with the decrease in the similarity difference to the normal control group and the increase in the number of operational taxonomic units (OTUs) shared with the normal control group. Additionally, adjuvant therapy with Dingguier umbilical paste also showed long action duration and increased OTUs number. These results indicated that Dingguier umbilical paste has the effect in restoring the micro-ecosystem of unbalanced intestinal bacteria. Intestinal flora may be one of major targets for the applicator therapy for the infant diarrhea, but not for the single oral traditional Chinese medicine for infant diarrhea.

Wet-plate culture studies of Penicillium sp. PT95 and Q1 for mass production of sclerotia.

Penicillium sp. PT95 and Q1 strains were able to form abundant orange, sand-shaped sclerotia in which carotenoids were accumulated. To determine the potential availability of the wet-plate method for mass production of sclerotia, nine kinds of liquid media were used culture the PT95 and Q1 strains. The results of the wet-plate culture showed that on 25% glycerol nitrate broth medium, the growth of both strains was relatively slow, and no sclerotia were found. Q1 strain cultured on Czapek's yeast extract broth medium could not form sclerotia. On other media, both strains could form sclerotia. For PT95 strain, the highest sclerotial biomass (380 mg plate(-1) ) and carotenoids yield (20.88 µg plate(-1) ) could be obtained on Czapek's yeast extract broth and Georgiou's liquid medium, respectively. For Q1 strain, malt extract broth medium gave the highest sclerotial biomass (340 mg plate(-1) ) and omitting iron Joham's liquid medium gave the highest carotenoids yield (18.29 µg plate(-1) ). The results from this study suggest the potential usage of wet-plate method in the mass production of sclerotia of the PT95 and Q1 strains.

Effect of copper-induced oxidative stress on sclerotial differentiation and antioxidants contents of Penicillium thomii Q1.

Penicillium thomii Q1 strain was able to form abundant orange, sand-shaped sclerotia in which carotenoids were accumulated. The aim of this work was to determine the effects of copper-induced oxidative stress on the sclerotial differentiation, biosynthesis of some endogenous antioxidants, and the activities of some antioxidative enzymes of Q1 strain. The results showed that the oxidative stress induced by copper was clearly dependent on the CuSO4 concentrations in media, and characterized by the initiation of lipid peroxidation. Under the copper-induced oxidative stress conditions, the time of exudates initiation, sclerotial initiation and sclerotial maturation of Q1 strain were advanced in 1-2 days. The analytical results of sclerotial biomass, carotenoids, and ascorbate contents showed that copper-induced oxidative stress favored the sclerotial differentiation and biosynthesis of carotenoids and ascorbate. The oxidative stress induced by a lower amount of CuSO4 in media could enhance significantly the superoxide dismutase and catalase activities of Q1 strain.