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Abstract Milk, as a dietary supplement, is crucial for maintaining health and potentially preventing disease throughout life. Both traditional Chinese medicine and modern nutritional science have revealed that milk from different mammals can benefit humans, exhibiting distinct medicinal functions. It can be inferred that milk contains not only multiple nutrients but also an abundance of bioactive components that have health benefits for milk consumers. However, limited studies have focused on the differences in bioactive metabolites in milk derived from various ruminants and their distinct medical functions. Here, we present a comprehensive review of the diversity of microbial metabolites and their associated health benefits, which are primarily shaped by the rumen‐mammary gland axis. Our findings reveal the pivotal role played by microbial metabolites in facilitating the microbiome's influence on human physiology. Finally, we conclude that ruminant milk may offer a path to harness these metabolites’ therapeutic benefits. To increase these metabolites in milk, there is need to design dietary supplements for dairy ruminants, which could enhance milk's medicinal value and aroma, revolutionizing ruminant husbandry.

Abstract Propose The biological function of ZYG11B is still unclear, and few studies on ZYG11B in colorectal cancer were reported. The purpose of our research is to detect the biological functions of ZYG11B in colorectal cancer through The Cancer Genome Atlas (TCGA) database online and the vitro cell experiments. Methods The information of ZYG11B in colorectal cancer were downloaded from TCGA database. The bioinformatics analysis has been utilized to examine the expression, functional enrichment, association of immune, clinicopathological characteristics and diagnostic prognostic value. CCK-8 and apoptosis assays have been utilized to identify the abilities of progression and apoptosis. The abilities of invasion and migration were detected by transwell assay. Results In contrast to adjacent normal tissues, colorectal cancer tissues exhibited a notably diminished expression of ZYG11B (p

From January 2022 to November 2022, sporadic psittacosis occurred in Lishui city, China. The patients were presented with fever, cough, and pulmonary infiltration. Their clinical symptoms were not relieved after receiving cephalosporin, penicillin, beta-lactamase inhibitors, and quinolones. Metagenomic next-generation sequencing of bronchoalveolar lavage fluid samples from the patients revealed Chlamydia psittaci infection. Then, three C. psittaci strains were isolated from the patients. Their whole genome sequences (WGSs) were obtained, and a core genome multilocus sequence typing (cgMLST) method was developed to study the population structure of C. psittaci. Using the constructed cgMLST method, 72 WGSs were divided into four related groups and ten sub-clusters. The Lishui strains formed a unique population of C. psittaci, which might represent a new variant of C. psittaci. In vitro antimicrobial susceptibility testing suggested that the Lishui strains were sensitive to tetracycline, macrolides, quinolones, and no drug-resistance was observed.

Various strategies have been explored to mitigate the impact of harmful algal blooms (HABs). While chemical and physical methods have traditionally been employed to regulate microalgal growth, their prolonged adverse effects on the ecosystem are a cause for concern. Recognizing the integral role of macroalgae within the ecosystem, this study reveals the anti-algal properties of solvent-based extracts derived from the red macroalga Pyropia haitanensis as a means of preventing microalgal blooms. In our investigation, we initially assessed the growth-inhibitory effects of methanol and acetone extracts from P. haitanensis on five microalgae known to contribute to bloom-formation. Significantly reduced growth was observed in all microalgal species when inoculated with both methanol and acetone extracts. Further analysis revealed the effectiveness of the methanol extract (ME), and further fractionation with petroleum ether (PE), ethyl acetate (EA), and n-butanol (NB) for testing against Skeletonema costatum and Pseudo-nitzschia pungens. The methanol fractions exhibited strong inhibition, resulting in the complete elimination of both microalgae after 96 hours of exposure to PE, EA, and NB extracts. Gas Chromatography-Mass Spectroscopy (GC-MS) analysis of the ME and its solvent fractions identified 49 confirmed compounds. These compounds are likely potential contributors to the observed inhibition of microalgal growth. In conclusion, our findings suggest that solvent extracts from P. haitanensis possess substantial potential for the control of HABs, offering a promising avenue for further research and application in ecosystem management.

Pasteurella multocida is a zoonotic pathogen causing serious diseases in humans and animals. Here, we report P. multocida from wildlife on China's Qinghai-Tibet plateau with a novel capsular serotype, forming a single branch on the core-genome phylogenetic tree: four strains isolated from dead Himalayan marmot (Marmota himalayana) and one genome assembled from metagenomic sequencing of a dead Woolly hare (Lepus oiostolus). Four of the strains were identified as subspecies multocida and one was septica. The mouse model showed that the challenge strain killed mice within 24 h at an infectious dose of less than 300 bacteria. The short disease course is comparable to septicemic plague: the host has died before more severe pathological changes could take place. Though pathological changes were relatively mild, cytokine storm was obvious with a significant rise of IL-12p70, IL-6, TNF-αand IL-10 (P

Lysinibacillus sphaericus, as an insect pathogen, is a ubiquitous Gram-positive bacterium present in the environment. It is often considered to be contaminating bacteria. L. sphaericus has been reported to cause infectious diseases in humans relatively rarely. We report a rare case of bacteremia due to L. sphaericus in a person living with HIV, which is also the first reported case of bacteremia caused by L. sphaericus in China. L. sphaericus easily causes infection in immunocompromised individuals. We found that L. sphaericus and Lysinibacillus fusiformis could not be distinguished by their 16S ribosomal RNA gene sequence. We performed a genome-wide analysis of the isolated strains of this case and predicted the virulence factors. Finally, L. sphaericus was confirmed. According to antimicrobial susceptibility test, the strain was found to be sensitive to levofloxacin and vancomycin but resistant to penicillin. Greater attention to L. sphaericus infection should be paid and immunocompromised populations should be protected from L. sphaericus infection.

ABSTRACTDietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95–1.05 in group A to D (all P

The enteroinvasive bacterium Shigella flexneri is known as a highly host-adapted human pathogen. There had been no known other reservoirs reported until recently. Here 34 isolates obtained from animals (yaks, dairy cows and beef cattle) from 2016 to 2017 and 268 human S. flexneri isolates from China were sequenced to determine the relationships between animal and human isolates and infer the evolutionary history of animal-associated S. flexneri. The 18 animal isolates (15 yak and 3 beef cattle isolates) in PG1 were separated into 4 lineages, and the 16 animal isolates (1 yak, 5 beef cattle and 10 dairy cow isolates) in PG3 were clustered in 8 lineages. The most recent human isolates from China belonged to PG3 whereas Chinese isolates from the 1950s–1960s belonged to PG1. PG1 S. flexneri may has been transmitted to the yaks during PG1 circulation in the human population in China and has remained in the yak population since, while PG3 S. flexneri in animals were likely recent transmissions from the human population. Increased stability of the large virulence plasmid and acquisition of abundant antimicrobial resistance determinants may have enabled PG3 to expand globally and replaced PG1 in China. Our study confirms that animals may act as a reservoir for S. flexneri. Genomic analysis revealed the evolutionary history of multiple S. flexneri lineages in animals and humans in China. However, further studies are required to determine the public health threat of S. flexneri from animals.

Ambo dajingensis HH Liu, Z Wang, YH Gao & CP Chen, sp. nov. is described as a new species in samples collected from sand grains at Dajing Beach, Ningde City, Fujian Province, China. Morphological details of the new species with respect to valve shape, size and valve ultrastructure are presented based on light microscopy (LM) and scanning electron microscopy (SEM). The main features of Ambo dajingensis under a light microscope are elongated elliptic valves with rounded apices, two internal costae on the valve and rectangular in girdle views. SEM observation showed that externally, the frustules are comprised of two valves with a relatively deep mantle and a transition between the valve faces. Small, flabelliform spines are present along the valve margin. Internally, the valves are divided into three sectors by robust costae, which penetrate the whole valve lumen and are thickest at the mantle interior and thinner toward the center. The sternum is narrow and linear, visible only in the valve apex, set off by costae. The striae are comprised of small, round areolae and they are parallel in the middle to slightly radiate at the apices. The new species is compared with other species in the genus Ambo.

Abstract 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.

Qinzhou Bay is a tropical semiclosed bay with the highest phytoplankton diversity and a high frequency of harmful algal blooms (HABs) in the Guangxi coastal area, located north of the Beibu Gulf. Phaeocystis globosa is a typical HAB species in the Guangxi coastal area, and blooms mainly occur in autumn and winter. The causes of these blooms and the succession of phytoplankton assemblages related to the blooms are complicated and not fully understood. Therefore, a continuous survey was conducted monthly from October 2018 to March 2019 to study the succession of the phytoplankton community in Qinzhou Bay and its relationship with environmental variables in this area. The results revealed that the dynamics of the phytoplankton assemblages varied significantly with time, and P. globosa was the most frequent dominant species in five of these voyages, with the highest cell density of 3.79 ± 1.34 × 106 cells/L in January. Chaetoceros species had a high density and were a dominant species associated with P. globosa in the early stage, while they were replaced by Guinardia striata when the density of P. globosa increased rapidly in January, and the abundance of dinoflagellates increased after the decline in P. globosa. The diversity index indicated that the community structure was more stable from October to December, while the sharp increase in P. globosa in January caused a decline in phytoplankton diversity. The redundancy analysis (RDA) results revealed that the phytoplankton community structure and its variation were mainly affected by hydrological and chemical factors, including DIN/DIP, temperature, DSi, DIP and DSi/DIP. Furthermore, we inferred that phosphorus (P) was the key factor limiting the colony formation of P. globosa, and P limitation prevented the outbreak of blooms. This research may provide more insight into the mechanisms driving and prevention of P. globosa blooms.

Although estuarine diatoms have a wide range of salt tolerance, they are often severely stressed by elevated salt concentrations. It remains poorly understood how estuarine diatoms maintain ionic homeostasis under high-salinity conditions. Using a scanning ion-selective electrode technique, this study determined the fluxes of H+, Na+, and K+ involved in the acclimatization of the estuarine diatom Coscinodiscus centralis Ehrenberg after an elevation in salinity from 15 psu to 35 psu. The C. centralis cells exhibited marked H+ effluxes after a transient treatment (TT, 30 min) and short-term treatment (ST, 24 h). However, a drastic shift of H+ efflux toward an influx was induced in the long-term treatment (LT, 10 days). The Na+ flux under TT, ST, and LT salinity conditions was found to accelerate the Na+ efflux. More pronounced effects were observed under the ST and LT salinity conditions compared to the TT salinity condition. The K+ influx showed a significant increase under the LT salinity condition. However, the salinity-induced Na+/H+ exchange in the estuarine diatom was inhibited by amiloride and sodium orthovanadate. These results indicate that the Na+ extrusion in salt-stressed cells is mainly the result of an active Na+/H+ antiport across the plasma membrane. The pattern of ion fluxes under the TT and ST salinity conditions were different from those under the LT salinity conditions, suggesting an incomplete regulation of the acclimation process in the estuarine diatom under short-term salinity stress.

China is one of the countries with the richest wildlife population. The large variety of widely distributed species act as natural or susceptible hosts for numerous infectious diseases. It is estimated that there are more than 1.2 million unknown virus species in China, and there might be 10,000–30,000 unknown bacteria in wild mammals on the Qinghai-Tibet Plateau alone. There are no less than 600,000 species of animal-borne parasites and approximately 2 million species of fungi worldwide. With rapid economic growth and globalization, humans and wildlife interact more frequently, which enhances the probability of wildlife-borne pathogens infecting humans. The occurrence of animal-borne infectious diseases will become the “new normal” we have to face in the future. Therefore, research should be carried out on wildlife-borne microorganisms and the prevention and control of emerging infectious diseases to establish an analytical framework and an evaluation technology system for risk assessment and early warning of potential animal-borne emerging infectious diseases. This will not only improve our understanding of wildlife-borne microbial communities but also enable in-depth analysis, discovery, early warning, and even prediction of major animal-borne emerging infectious diseases that might occur in the future. Furthermore, this research will reduce response times, minimize the social and economic impact and losses, enable interventions related to the emergence or spread of the disease as early as possible, and comprehensively improve our management of infectious disease outbreaks.

ABSTRACT 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.

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.

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.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a rare and severe form of end-stage liver disease with high mortality; gut microbes are strongly associated with the development of this severe liver disease but the exact association is unclear. Artificial liver support systems (ALSS) are clinically important in prolonging the waiting time for liver transplantation and in aiding drug therapy to achieve remission. The aim of this study was to investigate the effect of ALSS on the abundance and diversity of microorganisms in the gut of HBV-ACLF patients. In this study, 109 stool samples were collected from patients with hepatitis B virus-associated acute chronic liver failure (HBV-ACLF) for 16S rRNA sequencing. Among them, 44 samples were from patients treated with ALSS therapy as an adjunct to standard medical treatment (SMT) and 65 were from patients receiving SMT only. Analysis of the sequencing results suggested that there were significant differences in the abundance and diversity of gut microbiota between the with-ALSS and without-ALSS groups (p < 0.05). The operational taxonomic units and Shannon indexes indicated that the diversity and abundance of the gut microbiome, while decreasing after the first ALSS treatment, gradually increased after an increase in the number of ALSS therapies. The overall proportion of HBV-ACLF patients with coinfection was 27.59%; the coinfection can reduce the abundance of the Bacteroidetes phylum in the microbiome significantly whereas Proteobacteria were highly enriched. After ALSS therapy, HBV-ACLF patients had a decrease in potentially harmful bacteria, an increase in potentially beneficial bacteria, an increase in the diversity of the intestinal microbiota, and the intestinal microecological disorders were corrected to a certain extent. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) levels, as well as the international normalized ratio (INR), showed a decreasing trend whereas plasminogen activity (PTA) increased and the condition of patients with HBV-ACLF progressed in a favorable direction. In addition, the abundance of Blautia and Coprococcus was negatively correlated with TBIL and INR, positively correlated with PTA, and positively correlated with disease recovery. Our study shows that ALSS can alter the composition of the gut microbiota and have an ameliorating effect on the gut microecological imbalance in HBV-ACLF patients. It is worth mentioning that Blautia and Coprococcus may have great potential as biomarkers.

IntroductionThe 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 PresentationThe 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.ConclusionThis 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.

ABSTRACTThe source of secondary lower respiratory tract bacterial infections in influenza patients is not fully understood. A case–control study was conducted during the 2017–2018 influenza epidemic period in Beijing, China. Nasopharyngeal swabs were collected from 52 virologically confirmed influenza patients and 24 healthy medical staff. The nasopharyngeal microbiota taxonomic composition was analysed using high-throughput sequencing of the 16S rRNA gene V3–V4 regions. The super-dominant pathobiontic bacterial genus (SDPG) was defined as that accounting for >50% of sequences in a nasopharyngeal swab. We attempted to isolate bacteria of this genus from both nasopharyngeal swabs and lower-respiratory tract samples and analyse their genetic similarities. We observed a significantly lower taxonomy richness in influenza cases compared with healthy controls. A SDPG was detected in 61% of severe cases but in only 24% of mild cases and 29% of healthy controls. In 10 cases, the species isolated from lower-respiratory tract infection sites were identified as belonging to the nasopharyngeal microbiota SDPG. Genetically identical strains were isolated from both nasopharyngeal swabs and lower-respiratory tract infection sites, including 23 Acinetobacter baumannii strains from six severe cases, six Klebsiella pneumoniae strains from two severe cases, five Pseudomonas aeruginosa strains from one severe and one mild case, and four Corynebacterium striatum strains from two severe cases. The SDPG in the nasopharyngeal microbiota are the likely cause of subsequent infection in influenza patients.

Boosting and prolonging SARS-CoV-2 vaccine-elicited immunity is paramount for containing the COVID-19 pandemic, which wanes substantially within months after vaccination. Here we demonstrate that the unique strain of probiotic Lactobacillus plantarum GUANKE (LPG) could promote SARS-CoV-2-specific immune responses in both effective and memory phases through enhancing interferon signaling and suppressing apoptotic and inflammatory pathways. Interestingly, oral LPG administration promoted SARS-CoV-2 neutralization antibodies even 6 months after immunization. Furthermore, when LPG was given immediately after SARS-CoV-2 vaccine inoculation, specific neutralization antibodies could be boosted >8-fold in bronchoalveolar lavage (BAL) and >2-fold in sera, T-cell responses were persistent and stable for a prolonged period both in BAL and the spleen. Transcriptional analyses showed that oral application of LPG mobilized immune responses in the mucosal and systemic compartments; in particular, gut-spleen and gut-lung immune axes were observed. These results suggest that LPG could be applied in combination with SARS-CoV-2 vaccines to boost and prolong both the effective and memory immune responses in mucosal and systemic compartments, thereby improving the efficacy of SARS-CoV-2 vaccination.

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.

The relationship between the progression of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and the gut microbiota is poorly understood, and an HBV-ACLF-related microbiome has yet to be identified. In this study alterations in the fecal microbiome of 91 patients with HBV-ACLF (109 stool samples), including a cohort of nine patients at different stages of HBV-ACLF, were determined by high-throughput 16S rDNA sequencing. The operational taxonomic units and Shannon indexes indicated that the diversity and abundance of the gut microbiome significantly decreased with the progression of HBV-ACLF (p

Cancer is becoming the leading cause of death and a major public health problem. Although many advanced treatment strategies are currently in use, the general prognosis of cancer patients remains dismal due to the high frequency of recurrence, metastasis. The identification of effective biomarkers is important for predicting survival of cancer patients and improving treatment efficacy. In this study, we comprehensively analyzed WNT1-inducible-signaling pathway protein 1 (WISP1) expression and explored its correlation with prognosis in pan-cancer using tumor IMmune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). We also examined correlations between WISP1 and immunocyte infiltration using TIMER. We identified genes co-expressed with WISP1 using the LinkedOmics database and analyzed associated gene ontology using Metascape. Finally, we constructed protein-protein interaction networks and examined correlations between genes co-expressed with WISP1 and immunocyte infiltration in pan-cancer. WISP1 level differed between human pan-cancer tissues and normal tissues, indicating its potential as a prognostic biomarker. WISP1 expression was correlated with tumor purity and immunocyte infiltration, especially monocyte-macrophage trafficking and M2 polarization. Genes co-expressed with WISP1 were mainly associated with extracellular matrix organization, with collagen members COL6A3, COL5A1, and COL8A1 being key genes correlated with macrophage infiltration and M2 polarization in pan-cancer. Conversely, in certain types of cancer with better prognoses, WISP1 was associated with low M2 macrophage infiltration. These results suggest that WISP1 affect clinical prognosis through associations with tumor purity, immune cell infiltration, and macrophage M2 polarization in pan-cancer, with collagen member proteins may serving as effector molecules of WISP1.

Currently, Gram-negative bacteria have developed multidrug and broad-spectrum drug resistance, and the numbers of species and strains carrying mcr or blaNDM genes are increasing. In this study, mcr-1 and blaNDM distribution of 12,858 Gram-negative bacteria isolated from wildlife, patients, livestock, poultry and environment in 14 provinces of China from 2010 to 2019 and the antibiotics resistance in regard to polymyxins (polymyxin B and colistin) and carbapenems of positive strains were investigated. A total of 70 strains of 10 species carried the mcr-1 gene, positive rates of patients, livestock and poultry, and environmental strains were 0.62% (36/5,828), 4.07% (29/712), 5.43% (5/92), respectively. Six strains of 3 species carrying the blaNDM gene all came from patients 0.10% (6/5,828). Two new mcr-1 gene variants (GenBank: MK965883, MK965884) were identified, one of which contains premature stop codon. The drug susceptibility results showed that all mcr-1 carriers were sensitive to carbapenems, among which, 66 strains were resistant and 4 were sensitive to polymyxins. The strains with the blaNDM gene had different degrees of resistance to carbapenems and were sensitive to polymyxins. The findings that species carrying mcr-1 or blaNDM genes were limited and mostly normal flora of opportunistic or low pathogenic organisms indicated that transfer of mcr-1 and blaNDM genes between bacteria was relatively limited in China. The none detection among wildlife compared with other sources supports the speculation that the emergence of and increase in polymyxins and carbapenem-resistant strains was mainly related to the selective pressure of antibiotics.

Yersinia enterocolitica is thought to not significantly contribute to diarrheal disease in China, but evidence substantiating this claim is limited. We determined the prevalence of Y. enterocolitica infection and strain types present among children

Yersinia enterocolitica is a major agent of foodborne diseases worldwide. Prophage plays an important role in the genetic evolution of the bacterial genome. Little is known about the genetic information about prophages in the genome of Y. enterocolitica, and no pathogenic Y. enterocolitica prophages have been described. In this study, we induced and described the genomes of six prophages from pathogenic Y. enterocolitica for the first time. Phylogenetic analysis based on whole genome sequencing revealed that these novel Yersinia phages are genetically distinct from the previously reported phages, showing considerable genetic diversity. Interestingly, the prophages induced from O:3 and O:9 Y. enterocolitica showed different genomic sequences and morphology but highly conserved among the same serotype strains, which classified into two diverse clusters. The three long-tailed Myoviridae prophages induced from serotype O:3 Y. enterocolitica were highly conserved, shared ≥99.99% identity and forming genotypic cluster A; the three Podoviridae prophages induced from the serotype O:9 strains formed cluster B, also shared more than 99.90% identity with one another. Cluster A was most closely related to O:5 non-pathogenic Y. enterocolitica prophage PY54 (61.72% identity). The genetic polymorphism of these two kinds of prophages and highly conserved among the same serotype strains, suggested a possible shared evolutionary past for these phages: originated from distinct ancestors, and entered pathogenic Y. enterocolitica as extrachromosomal genetic components during evolution when facing selective pressure. These results are critically important for further understanding of phage roles in host physiology and the pathology of disease.

Abstract Larus ridibundus, a migratory wild bird, has become one of the most popular gull species in southwest China in recent years. There has been no information on the gut microbiota and intestinal pathogenic bacteria configuration in wild L. ridibundus, even though the public are in close contact with this bird. In this study, 16S rRNA amplicon‐sequencing methods were used to describe the microbial community structure and intestinal pathogenic bacteria were isolated to identify their characteristics. The taxonomic results revealed that Firmicutes (86%), Proteobacteria (10%), and Tenericutes (3%) were the three most abundant phyla in the gut of L. ridibundus. Enterococcaceae, Enterobacteriaceae, and Mycoplasmataceae were the most predominant families, respectively. The number of operational taxonomic units (OTUs), the richness estimates and diversity indices of microbiota, was statistically different (p 0.05) between all the fecal samples. The most frequently isolated intestinal pathogenic bacteria from L. ridibundus were enteropathogenic Escherichia coli (32%) and Salmonella (21%). Pulsed‐field gel electrophoresis (PFGE) results of Salmonella species revealed a high degree of similarity between isolates, which was not observed for other species. None of the potentially pathogenic isolates were identical to human‐isolated counterparts suggesting that there was little cross‐infection between humans and gulls, despite close proximity. In brief, this study provided a baseline for future L. ridibundus microbiology analysis, and made an understanding of the intestinal bacterial community structure and diversity.

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.

A case of primary pneumonic plague (PPP) caused by Yersinia pestis is reported. This case occurred in the largest plague area in China. The patient died after contact with a dog that had captured an infected marmot. Three of 151 contacts were shown to be positive for antibody against F1 antigen by indirect hemagglutination assay, but none had clinical symptoms. There was no secondary case.

Yersinia enterocolitica encodes a chromosomal AmpC β-lactamase under the regulation of the classical ampR-ampC system. To obtain a further understanding to the role of low-molecular-mass penicillin-binding proteins (LMM PBPs) including PBP4, PBP5, PBP6, and PBP7, as well as NagZ and AmpR in ampC regulation of Y. enterocolitica, series of single/multiple mutant strains were systematically constructed and the ampC expression levels were determined by luxCDABE reporter system, reverse transcription-PCR (RT-PCR) and β-lactamase activity test. Sequential deletion of PBP5 and other LMM PBPs result in a continuously growing of ampC expression level, the β-lactamse activity of quadruple deletion strain YEΔ4Δ5Δ6Δ7 (pbp4, pbp5, pbp6, and pbp7 inactivated) is approached to the YEΔD123 (ampD1, ampD2, and ampD3 inactivated). Deletion of nagZ gene caused two completely different results in YEΔD123 and YEΔ4Δ5Δ6Δ7, NagZ is indispensable for YEΔ4Δ5Δ6Δ7 ampC derepression phenotype but dispensable for YEΔD123. AmpR is essential for ampC hyperproduction in these two types of strains, inactivation of AmpR notable reduced the ampC expression level in both YEΔD123 and YEΔ4Δ5Δ6Δ7.

Pathogenic Yersinia enterocolitica is widely distributed in China where the primary bio-serotypes are 3/O: 3 and 2/O: 9. Recently, the distribution of 2/O: 9 strains are being gradually replaced by 3/O: 3 strains where presently 3/O: 3 strains are the major pathogenic Y. enterocolitica in China. To identify the growth conditions and cytokines induced by Y. enterocolitica and providing some clues for this shift, we performed competitive growth in vitro and in vivo for these two bio-serotype strains; and we also compared the cytokines induced by them in infected BALB/C mice. We found 2/O: 9 strains grew more in vitro, while 3/O: 3 strains grew more in vivo regardless of using single cultures or mixed cultures. The cytokines induced by the two strains were similar: interleukin-6 (IL-6), IL-9, IL-13, granulocyte colony-stimulating factor (G-CSF), chemokines (KC), monocyte chemotactic protein 1 (MCP-1), macrophage inflammation protein-1α (MIP-1α), tumor necrosis factor-α (TNF-α), and RANTES were statistically up-regulated upon activation of normal T cells compared to the control. The cytokine values were higher in mixed infections than in single infections except for IL-6, G-CSF, and KC. The data illustrated the different growth of pathogenic Y. enterocolitica bio-serotype 3/O: 3 and 2/O: 9 in vitro and in vivo, and the cytokine changes induced by the two strains in infected BALB/C mice. The growth comparisons of two strains maybe reflect the higher pathogenic ability or resistance to host immune response for Y. enterocolitica bio-serotype 3/O: 3 and maybe it as one of the reason for bacteria shift.

BACKGROUND:Plague, a Yersinia pestis infection, is a fatal disease with tremendous transmission capacity. However, the mechanism of how the pathogen stays in a reservoir, circulates and then re-emerges is an enigma. METHODOLOGY/PRINCIPAL FINDINGS:We studied a plague outbreak caused by the construction of a large reservoir in southwest China followed 16-years' surveillance. CONCLUSIONS/SIGNIFICANCE:The results show the prevalence of plague within the natural plague focus is closely related to the stability of local ecology. Before and during the decade of construction the reservoir on the Nanpan River, no confirmed plague has ever emerged. With the impoundment of reservoir and destruction of drowned farmland and vegetation, the infected rodent population previously dispersed was concentrated together in a flood-free area and turned a rest focus alive. Human plague broke out after the enzootic plague via the flea bite. With the construction completed and ecology gradually of human residential environment, animal population and type of vegetation settling down to a new balance, the natural plague foci returned to a rest period. With the rodent density decreased as some of them died, the flea density increased as the rodents lived near or in local farm houses where had more domestic animals, and human has a more concentrated population. In contrast, in the Himalayan marmot foci of the Qinghai-Tibet Plateau in the Qilian Mountains. There are few human inhabitants and the local ecology is relatively stable; plague is prevalence, showing no rest period. Thus the plague can be significantly affected by ecological shifts.

In many gram negative bacilli, AmpD plays a key role in both cell well recycling pathway and β-lactamase regulation, inactivation of the ampD causes the accumulation of 1,6-anhydromuropeptides and results in the ampC overproduction. In Yersinia enterocolitica, the regulation of ampC expression may also relys on the ampR-ampC system, the role of AmpD in this species is still unkonwn. In this study, three AmpD homologues (AmpD1, AmpD2 and AmpD3) have been identified in complete sequence of strain Yersinia enterocolitica subsp. palearctica 105.5R(r). To understand the role of three AmpD homologues, several mutant strains were constructed and analyzed where a rare ampC regulation mechanism was observed: low-effective ampD2 and ampD3 cooperate with the high-effective ampD1 in the three levels regulation of ampC expression. Enterobacteriaceae was used to be supposed to regulate ampC expression by two steps, three steps regulation was only observed in Pseudomonas aeruginosa. In this study, we first reported that Enterobacteriaceae Y.enterocolitica can also possess a three steps stepwise regulation mechanism, regulating the ampC expression precisely.

API 20E strip test, the standard for Enterobacteriaceae identification, is not sufficient to discriminate some Yersinia species for some unstable biochemical reactions and the same biochemical profile presented in some species, e.g. Yersinia ferderiksenii and Yersinia intermedia, which need a variety of molecular biology methods as auxiliaries for identification. The 16S rRNA gene is considered a valuable tool for assigning bacterial strains to species. However, the resolution of the 16S rRNA gene may be insufficient for discrimination because of the high similarity of sequences between some species and heterogeneity within copies at the intra-genomic level. In this study, for each strain we randomly selected five 16S rRNA gene clones from 768 Yersinia strains, and collected 3,840 sequences of the 16S rRNA gene from 10 species, which were divided into 439 patterns. The similarity among the five clones of 16S rRNA gene is over 99% for most strains. Identical sequences were found in strains of different species. A phylogenetic tree was constructed using the five 16S rRNA gene sequences for each strain where the phylogenetic classifications are consistent with biochemical tests; and species that are difficult to identify by biochemical phenotype can be differentiated. Most Yersinia strains form distinct groups within each species. However Yersinia kristensenii, a heterogeneous species, clusters with some Yersinia enterocolitica and Yersinia ferderiksenii/intermedia strains, while not affecting the overall efficiency of this species classification. In conclusion, through analysis derived from integrated information from multiple 16S rRNA gene sequences, the discrimination ability of Yersinia species is improved using our method.

In China, great differences in economy, social characteristics and hygiene exist between developing and developed regions. A comparative study of infectious diarrhea between two regions was needed. Three groups of diarrheal patients were collected: children ≤5 year-olds from Beijing (developed region) and Henan Province (developing region), and adults over 18 year-olds from Beijing. A questionnaire was used to survey and feces samples were examined for 16 enteropathogens. We enrolled 1422 children and 1047 adults from developed region and 755 children from developing region. Virus positive rates were 32.98% for children and 23.67% for adults in developed region. The most prevalent pathogen for children was rotavirus whereas for adults was norovirus. Bacterial isolation rates were 13.92% for children from developed region, while 29.14% for children from the developing regions. For the greatest difference, Shigella accounted for 50.79% and was the dominant pathogen in the developing region, whereas in the developed region it was only 1.45%. There was no significant relationship between the local levels of development with diarrheogenic Escherichia coli (DEC) categories. But it was seen the notable differences between the population with different age: enteropathogenic E.coli (EPEC) and enteroaggregative E.coli (EAggEC) were the primary classes of DEC in children from both regions, whereas it was enterotoxigenic E.coli (ETEC) in adults. The symptoms of Shigella and Salmonella infection, such as bloody stools, white blood cells (WBC) and red blood cells (RBC) positivity and fever were similar in children, which may lead to the misidentification. Yersinia enterocolitica and shiga toxin-producing E.coli (STEC) infections were firstly reported in Beijing. There was a large difference in etiology of bacterial diarrhea between children in developing and developed regions of China.