Relationship Between Climate Change and Marmot Plague of Marmota himalayana Plague Focus - the Altun Mountains of the Qinghai-Xizang Plateau, China, 2000-2022.

Introduction: Plague is a zoonotic disease that occurs naturally in specific geographic areas. Climate change can influence the populations of the plague host or vector, leading to variations in the occurrence and epidemiology of plague in animals. Methods: In this study, we collected meteorological and plague epidemiological data from the Marmota himalayana plague focus in the Altun Mountains of the Qinghai-Xizang Plateau. The data spanned from 2000 to 2022. We describe the climatic factors and plague epidemic conditions and we describe their analysis by Pearson's correlation. Results: During the period from 2000 to 2022, the isolation rates of Yersinia pestis (Y.pestis) from marmots and fleas were 9.27% (451/4,864) and 7.17% (118/1,646), respectively. Additionally, we observed a positive rate of F1 antibody of 11.25% (443/3,937) in marmots and 18.16% (142/782) in dogs. With regards to climate, there was little variation, and a decreasing trend in blowing-sand days was observed. The temperature in the previous year showed a negative correlation with the Y. pestis isolation rate in marmots (r=-0.555, P=0.011) and the positive rate of F1 antibody in marmots (r=-0.552, P=0.012) in the current year. The average annual precipitation in the previous two years showed a positive correlation with marmot density (r=0.514, P=0.024), while blowing-sand days showed a negative correlation with marmot density (r=-0.701, P=0.001). Furthermore, the average annual precipitation in the previous three years showed a positive correlation with the isolation rate of Y. pestis from marmots (r=0.666, P=0.003), and blowing-sand days showed a negative correlation with marmot density (r=-0.597, P=0.009). Conclusions: The findings of this study indicate that there is a hysteresis effect of climate change on the prevalence of plague. Therefore, monitoring climate conditions can offer significant insights for implementing timely preventive and control measures to combat plague epidemics.

The complex genomic diversity of Yersinia pestis on the long-term plague foci in Qinghai-Tibet plateau.

Plague is a typical natural focus disease that circulates in different ecology of vectors and reservoir hosts. We conducted genomic population and phylogenetic analyses of the Yersinia pestis collected from the 12 natural plague foci in China with more than 20 kinds of hosts and vectors. Different ecological landscapes with specific hosts, vectors, and habitat which shape various niches for Y. pestis. The phylogeographic diversity of Y. pestis in different kinds plague foci in China showed host niches adaptation. Most natural plague foci strains are region-and focus-specific, with one predominant subpopulation; but the isolates from the Qinghai-Tibet plateau harbor a higher genetic diversity than other foci. The Y. pestis from Marmota himalayana plague foci are defined as the ancestors of different populations at the root of the evolutionary tree, suggesting several different evolutionary paths to other foci. It has the largest pan-genome and widest SNP distances with most accessory genes enriched in mobilome functions (prophages, transposons). Geological barriers play an important role in the maintenance of local Y. pestis species and block the introduction of non-native strains. This study provides new insights into the control of plague outbreaks and epidemics, deepened the understanding of the evolutionary history of MHPF (M. himalayana plague focus) in China. The population structure and identify clades among different natural foci of China renewed the space cognition of the plague.

Identification of Novel Bartonella washoensis Sequence Type 22 in Marmota himalayana - Jiuquan City, Gansu Province, China, 2021-2022.

What is already known about this topic?: The prevalence of rodent-adapted Bartonella species has been increasing significantly. However, the specific Bartonella species carried by Marmota himalayana (M. himalayana), a large rodent species, and the potential risk it poses to human populations remain unknown. What is added by this report?: Bartonella washoensis (B. washoensis), associated with human endocarditis, was initially identified in M. himalayana, exhibiting a detection rate of approximately one-third and demonstrating a predilection for the heart and lungs. The discovery of the novel Sequence Type 22 has expanded both the isolation source and genetic lineage of B. washoensis. What are the implications for public health practice?: Individuals residing within the M. himalayana plague focus are at an elevated risk for B. washoensis infection. Consequently, there is a pressing need for public health warnings and efficient clinical case identification in this population.

Serological investigation of plague and brucellosis infection in Marmota himalayana plague foci in the Altun Mountains on the Qinghai-Tibet Plateau.

The Altun Mountains are among the most active regions of Marmota himalayana plague foci of the Qinghai-Tibet Plateau where animal plague is prevalent, whereas only three human cases have been found since 1960. Animal husbandry is the main income for the local economy; brucellosis appears sometimes in animals and less often in humans. In this study, a retrospective investigation of plague and brucellosis seroprevalence among humans and animals was conducted to improve prevention and control measures for the two diseases. Animal and human sera were collected for routine surveillance from 2018 to 2021 and screened for plague and brucellosis. Yersinia pestis F1 antibody was preliminarily screened by the colloidal gold method at the monitoring site to identify previous infections with positive serology. Previous plague infection was found in 3.2% (14/432) of the studied human population having close contact with livestock, which indicates evidence of exposure to the Yersinia antigen (dead or live pathogenic materials) in the Altun Mountains. Seroprevalence of brucellosis was higher in camels (6.2%) and sheepdogs (1.8%) than in other livestock such as cattle and sheep, suggesting a possible transmission route from secondary host animals to humans.

Epidemiological Characteristics of Human and Animal Plague in Yunnan Province, China, 1950 to 2020.

This study analyzed the epidemiological characteristics of 3,464 human plague cases and the distribution pattern of 4,968 Yersinia pestis isolates from humans, hosts, and vector insects from 1950 to 2020 among two natural plague foci in Yunnan Province, China. These foci include the Rattus flavipectus plague focus of the Yunnan, Guangdong, and Fujian provinces and the Apodemus chevrieri-Eothenomys miletus plague focus of the highlands of northwestern Yunnan Province. The case fatality rate for plague in humans was 18.39% (637/3,464), and the total isolation rate of Y. pestis was 0.17% (4,968/2,975,288). Despite that the frequency of human cases declined rapidly, the animal plague fluctuated greatly, alternating between activity and inactivity in these foci. The tendency among human cases can be divided into 4 stages, 1950 to 1955, 1956 to 1989, 1990 to 2005, and 2006 to 2020. Bubonic plague accounted for the majority of cases in Yunnan, where pneumonic and septicemic plague rarely occurred. The natural plague foci have been in a relatively active state due to the stability of local ecology. Dense human population and frequent contact with host animals contribute to the high risk of human infection. This study systematically analyzed the epidemic pattern of human plague and the distribution characteristics of Y. pestis in the natural plague foci in Yunnan, providing a scientific basis for further development and adjustment of plague prevention and control strategies. IMPORTANCE Yunnan is the origin of the third plague pandemic. The analysis of human and animal plague characteristics of plague foci in Yunnan enlightens the prevention and control of the next plague pandemics. The plague characteristics of Yunnan show that human plague occurred when animal plague reached a certain scale, and strengthened surveillance of animal plague and reducing the density of host animals and transmission vectors contribute to the prevention and control of human plague outbreaks. The phenomenon of alternation between the resting period and active period of plague foci in Yunnan further proves the endogenous preservation mechanism of plague.

Plague Outbreak of a Marmota himalayana Family Emerging from Hibernation.

In April 2021, a plague outbreak was identified within one Marmota himalayana family shortly after emerging from hibernation, during plague surveillance in the M. himalayana plague foci of the Qinghai-Tibet Plateau. A total of five marmots were found dead of Yersinia pestis near the same burrow; one live marmot was positive of Y. pestis fraction 1 (F1) antibody. Comparative genome analysis shows that few single nucleotide polymorphisms were detected among the nine strains, indicating the same origin of the outbreak. The survived marmot shows a high titer of F1 antibody, higher than the mean titer of all marmots during the 2021 monitoring period (W = 391.00, Z = 2.81, p < 0.01). Marmots live with Y. pestis during hibernation when the pathogen is inhibited by hypothermia. But they wake up during or just after hibernation with body temperature rising to 37°C, when Y. pestis goes through optimal growth temperature, increases virulence, and causes death in marmots. A previous report has shown human plague cases caused by excavating marmots during winter; combined, this study shows the high risk of hibernation marmot carrying Y. pestis. This analysis provides new insights into the transmission of the highly virulent Y. pestis in M. himalayana plague foci and drives further effort upon plague control during hibernation.

First Case Report of Human Plague Caused by Excavation, Skinning, and Eating of a Hibernating Marmot (Marmota himalayana).

Introduction: The Qinghai-Tibet Plateau is considered the most plague-heavy region in China, and skinning and eating marmots (Marmota himalayana) are understood to be the main exposure factors to plague. Yersinia pestis is relatively inactive during marmots' hibernation period. However, this case report shows plague infection risk is not reduced but rather increased during the marmot hibernation period if plague exposure is not brought under control. Case Presentation: The patient was a 45-year-old man who presented with high fever, swelling of axillary lymph nodes, and existing hand wounds on his right side. Y. pestis was isolated from his blood and lymphatic fluid. Hence, the patient was diagnosed with a confirmed case of bubonic plague. Later, his condition progressed to septicemic plague. Plague exposure through wounds and delays in appropriate treatment might have contributed to plague progression. Conclusion: This case report reveals that excavating a hibernating marmot is a significant transmission route of plague. Plague prevention and control measures are priority needs during the marmot hibernation period.

Anaplasma phagocytophilum in Marmota himalayana.

BACKGROUND: Human granulocytic anaplasmosis is a tick-borne zoonotic disease caused by Anaplasma phagocytophilum. Coinfections with A. phagocytophilum and other tick-borne pathogens are reported frequently, whereas the relationship between A. phagocytophilum and flea-borne Yersnia pestis is rarely concerned. RESULTS: A. phagocytophilum and Yersnia pestis were discovered within a Marmota himalayana found dead in the environment, as determined by 16S ribosomal rRNA sequencing. Comparative genomic analyses of marmot-derived A. phagocytophilum isolate demonstrated its similarities and a geographic isolation from other global strains. The 16S rRNA gene and GroEL amino acid sequence identity rates between marmot-derived A. phagocytophilum (JAHLEX000000000) and reference strain HZ (CP000235.1) are 99.73% (1490/1494) and 99.82% (549/550), respectively. 16S rRNA and groESL gene screenings show that A. phagocytophilum is widely distributed in marmots; the bacterium was more common in marmots found dead (24.59%, 15/61) than in captured marmots (19.21%, 29/151). We found a higher Y. pestis isolation rate in dead marmots harboring A. phagocytophilum than in those without it (2 = 4.047, p < 0.05). Marmot-derived A. phagocytophilum was able to live in L929 cells and BALB/c mice but did not propagate well. CONCLUSIONS: In this study, A. phagocytophilum was identified for the first time in Marmota himalayana, a predominant Yersinia pestis host. Our results provide initial evidence for M. himalayana being a reservoir for A. phagocytophilum; moreover, we found with the presence of A. phagocytophilum, marmots may be more vulnerable to plague. Humans are at risk for co-infection with both pathogens by exposure to such marmots.

Performance of Exergetic, Energetic and Techno-Economic Analyses on a Gas-Type Industrial Drying System of Black Tea.

The purpose of this research work is to perform detailed exergetic, energetic and techno-economic analysis of the black tea drying process in the gas-type industrial dryer. Exergy-energy and techno-economic methodology was applied to investigate the heat loss, exergetic and energetic performance, exergy efficiency, improvement potential rate, sustainability index and techno-economic performance of a drying system. The results showed that the heat loss of exhaust air in the late drying process played a main contributing role in the heat loss and exergy loss of the whole drying system. Therefore, the exergy efficiency of the initial drying period and the redrying period varied from 38.08% to 65.09% and 24.76% to 26.97%, respectively. In addition, the improvement potential rate and sustainability index of the whole system varied from 6.93 kW to 12.94 kW and 1.33 to 2.86, respectively. The improvement potential obtained in the present work indicated that the drying operation is greatly in need of exergy performance improvement. Finally, the net present value and payback period obtained from techno-economic analysis were 179,442.03 USD and 5.3 years, the result is useful for investors or contractors to refer to and make investment decisions.

Distribution and Characteristics of Human Plague Cases and Yersinia pestis Isolates from 4 Marmota Plague Foci, China, 1950-2019.

We analyzed epidemiologic characteristics and distribution of 1,067 human plague cases and 5,958 Yersinia pestis isolates collected from humans, host animals, and insect vectors during 1950-2019 in 4 Marmota plague foci in China. The case-fatality rate for plague in humans was 68.88%; the overall trend slowly decreased over time but fluctuated greatly. Most human cases (98.31%) and isolates (82.06%) identified from any source were from the Marmota himalayana plague focus. The tendency among human cases could be divided into 3 stages: 1950-1969, 1970-2003, and 2004-2019. The Marmota sibirica plague focus has not had identified human cases nor isolates since 1926. However, in the other 3 foci, Y. pestis continues to circulate among animal hosts; ecologic factors might affect local Y. pestis activity. Marmota plague foci are active in China, and the epidemic boundary is constantly expanding, posing a potential threat to domestic and global public health.

A Lytic Yersina pestis Bacteriophage Obtained From the Bone Marrow of Marmota himalayana in a Plague-Focus Area in China.

A lytic Yersinia pestis phage vB_YpP-YepMm (also named YepMm for briefly) was first isolated from the bone marrow of a Marmota himalayana who died of natural causes on the Qinghai-Tibet plateau in China. Based on its morphologic (isometric hexagonal head and short non-contractile conical tail) and genomic features, we classified it as belonging to the Podoviridae family. At the MOI of 10, YepMm reached maximum titers; and the one-step growth curve showed that the incubation period of the phage was about 10 min, the rise phase was about 80 min, and the lysis amount of the phage during the lysis period of 80 min was about 187 PFU/cell. The genome of the bacteriophage YepMm had nucleotide-sequence similarity of 99.99% to that of the Y. pestis bacteriophage Yep-phi characterized previously. Analyses of the biological characters showed that YepMm has a short latent period, strong lysis, and a broader lysis spectrum. It could infect Y. pestis, highly pathogenic bioserotype 1B/O:8 Y. enterocolitica, as well as serotype O:1b Y. pseudotuberculosis-the ancestor of Y. pestis. It could be further developed as an important biocontrol agent in pathogenic Yersinia spp. infection.

blaNDM and mcr-1 to mcr-5 Gene Distribution Characteristics in Gut Specimens from Different Regions of China.

Antibiotic resistance has become a global public health concern. To determine the distribution characteristics of mcr and blaNDM in China, gene screening was conducted directly from gut specimens sourced from livestock and poultry, poultry environments, human diarrhea patients, and wild animals from 10 regions, between 2010-2020. The positive rate was 5.09% (356/6991) for mcr and 0.41% (29/6991) for blaNDM, as detected in gut specimens from seven regions, throughout 2010 to 2019, but not detected in 2020. The detection rate of mcr showed significant differences among various sources: livestock and poultry (14.81%) > diarrhea patients (1.43%) > wild animals (0.36%). The detection rate of blaNDM was also higher in livestock and poultry (0.88%) than in diarrhea patients (0.17%), and this was undetected in wildlife. This is consistent with the relatively high detection rate of multiple mcr genotypes in livestock and poultry. All instances of coexistence of the mcr-1 and blaNDM genes, as well as coexistence of mcr genotypes within single specimens, and most new mcr subtypes came from livestock, and poultry environments. Our study indicates that the emergence of mcr and blaNDM genes in China is closely related to the selective pressure of carbapenem and polymyxin. The gene-based strategy is proposed to identify more resistance genes of concern, possibly providing guidance for the prevention and control of antimicrobial resistance dissemination.

Identification and Functional Enrichment Analysis of Potential Diagnostic and Therapeutic Targets in Adamantinomatous Craniopharyngioma.

Adamantinomatous craniopharyngioma (ACP) is a congenital epithelial tumor in the sellar region with benign histological manifestation but invasive. Currently, surgery is the main treatment for it, but its recurrence rate is high. Therefore, it is of great importance to explore the mechanism of occurrence and development of ACP and to identify new molecules. One gene expression profile, GSE94349, was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by the limma package. Gene set enrichment analysis was used to make enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, we performed the construction and analysis of the protein-protein interaction (PPI) network and significant module. The analysis of the GSE94349 dataset identified 109 DEGs, consisting of 80 upregulated genes and 29 downregulated genes in ACP samples compared with normal brain tissues. Functional and pathway enrichment analysis of DEGs provided a comprehensive overview of some major pathophysiological mechanisms in ACP: RNA polymerase II promoter, glutamate receptor binding, and so on. A total of 10 hub genes of DEGs were obtained from the PPI network, which provided potential therapeutic targets for the ACP. In summary, there were DEGs between ACP tissues and normal brain tissues, which may be involved in the mechanisms of occurrence and development of ACP, especially via the regulation of RNA polymerase II promoter and glutamate receptor binding. Key genes in DEGs could serve as new research targets for the diagnosis and treatment of ACP.

Screening and authentication of molecular markers in malignant glioblastoma based on gene expression profiles.

Glioblastoma (GBM) is a malignant tumor of the central nervous system with high mortality rates. Gene expression profiling may determine the chemosensitivity of GBMs. However, the molecular mechanisms underlying GBM remain to be determined. To screen the novel key genes in its occurrence and development, two glioma databases, GSE122498 and GSE104291, were analyzed in the present study. Bioinformatics analyses were performed using the Database for Annotation, Visualization and Integrated Discovery, the Search Tool for the Retrieval of Interacting Genes, Cytoscape, cBioPortal, and Gene Expression Profiling Interactive Analysis softwares. Patients with recurrent GBM showed worse overall survival rate. Overall, 341 differentially expressed genes (DEGs) were authenticated based on two microarray datasets, which were primarily enriched in 'cell division', 'mitotic nuclear division', 'DNA replication', 'nucleoplasm', 'cytosol, nucleus', 'protein binding', 'ATP binding', 'protein C-terminus binding', 'the cell cycle', 'DNA replication', 'oocyte meiosis' and 'valine'. The protein-protein interaction network was composed of 1,799 edges and 237 nodes. Its significant module had 10 hub genes, and CDK1, BUB1B, NDC80, NCAPG, BUB1, CCNB1, TOP2A, DLGAP5, ASPM and MELK were significantly associated with carcinogenesis and the development of GBM. The present study indicated that the DEGs and hub genes, identified based on bioinformatics analyses, had significant diagnostic value for patients with GBM.