Self-Assembled Nanocomposite DOX/TPOR4@CB[7]4 for Enhanced Synergistic Photodynamic Therapy and Chemotherapy in Neuroblastoma.

DOX/TPOR4@CB[7]4 was synthesized via self-assembly, and its physicochemical properties and ability to generate reactive oxygen species (ROS) were evaluated. The impact of photodynamic therapy on SH-SY5Y cells was assessed using the MTT assay, while flow cytometry analysis was employed to detect cell apoptosis. Confocal laser scanning microscopy was utilized to observe the intracellular distribution of DOX/TPOR4@CB[7]4 in SH-SY5Y cells. Additionally, fluorescence imaging of DOX/TPOR4@CB[7]4 in nude mice bearing SH-SY5Y tumors and examination of the combined effects of photodynamic and chemical therapies were conducted. The incorporation of CB[7] significantly enhanced the optical properties of DOX/TPOR4@CB[7]4, resulting in increased ROS production and pronounced toxicity towards SH-SY5Y cells. Moreover, both the apoptotic and mortality rates exhibited significant elevation. In vivo experiments demonstrated that tumor growth inhibition was most prominent in the DOX/TPOR4@CB[7]4 group. π-π interactions facilitated the binding between DOX and photosensitizer TPOR, with TPOR's naphthalene hydrophilic groups encapsulated within CB[7]'s cavity through host-guest interactions with CB[7]. Therefore, CB[7] can serve as a nanocarrier to enhance the combined application of chemical therapy and photodynamic therapy, thereby significantly improving treatment efficacy against neuroblastoma tumors.

Mechanisms of manipulating valley splitting in MoTe2/MnS2 van der Waals heterostructure by electric field and strains.

In this study, we discuss the tunability of valley splitting using first-principles calculations with a monolayer MoTe2 and layered ferromagnetic MnS2 heterostructure as an example. We observe that, due to the magnetic proximity effect (MPE) at the interface, a monolayer of MoTe2 can exhibit a significant valley splitting of 55.2 meV. The production of the interlayer dipoles with spin-adapted configuration could be the origin of MPE at the interface. Furthermore, the valley splitting can be regulated continuously by the perpendicular electric field and biaxial strain. Interestingly, the valley splitting increases with the increasing induced magnetic moments in MoTe2 by applying an electric field while the inverse laws are presented by applying biaxial strains, which indicates that the mechanisms of valley splitting manipulating in these two ways are quite different. The calculation results suggest that the electric field influences the electric dipole distributions at the interface, which determines the induced magnetic moments in monolayer MoTe2, and results in valley splitting variations. However, biaxial strains not only affect MPE at the interface but also the intrinsic spin splitting caused by spin-orbital coupling (SOC) effects of monolayer MoTe2 itself and the latter is even the dominating mechanism of valley splitting variations.

Spatiotemporal patterns and risk mapping of provincial hand, foot, and mouth disease in mainland China, 2014-2017.

Background: Hand, foot, and mouth disease (HFMD) has remained a serious public health threat since its first outbreak in China. Analyzing the province-level spatiotemporal distribution of HFMD and mapping the relative risk in mainland China will help determine high-risk provinces and periods of infection outbreaks for use in formulating new priority areas for prevention and control of this disease. Furthermore, our study examined the effect of air pollution on HFMD nationwide, which few studies have done thus far. Methods: Data were collected on the number of provincial monthly HFMD infections, air pollution, meteorological variables, and socioeconomic variables from 2014 to 2017 in mainland China. We used spatial autocorrelation to determine the aggregate distribution of HFMD incidence. Spatiotemporal patterns of HFMD were analyzed, risk maps were developed using the Bayesian spatiotemporal model, and the impact of potential influencing factors on HFMD was assessed. Results: In our study, from 2014 to 2017, the HFMD annual incidence rate in all provinces of mainland China ranged from 138.80 to 203.15 per 100,000 people, with an average annual incidence rate of 165.86. The temporal risk of HFMD for 31 Chinese provinces exhibited cyclical and seasonal characteristics. The southern and eastern provinces had the highest spatial relative risk (RR > 3) from 2014 to 2017. The HFMD incidence risk in provinces (Hunan, Hubei, and Chongqing) located in central China increased over time. Among the meteorological variables, except for the mean two-minute wind speed (RR 0.6878; 95% CI 0.5841, 0.8042), all other variables were risk factors for HFMD. High GDP per capita (RR 0.9922; 95% CI 0.9841, 0.9999) was a protective factor against HFMD. The higher the birth rate was (RR 1.0657; 95% CI 1.0185, 1.1150), the higher the risk of HFMD. Health workers per 1,000 people (RR 1.2010; 95% CI 1.0443, 1.3771) was positively correlated with HFMD. Conclusions: From 2014 to 2017, the central provinces (Hunan, Hubei, and Chongqing) gradually became high-risk regions for HFMD. The spatiotemporal pattern of HFMD risk may be partially attributed to meteorological and socioeconomic factors. The prevalence of HFMD in the central provinces requires attention, as prevention control efforts should be strengthened there.

Diagnosis and treatment of right ventricular metastasis from esophageal squamous cell carcinoma: An unusual case report and a literature review.

BACKGROUND: Right ventricular metastasis from esophageal squamous cell carcinoma is very rare and only seen in few case reports. Patients with cardiac metastasis have a poor prognosis with a median survival period of 4 weeks due to the lack of standardized and effective treatment guidelines. Therefore, we aimed to clarify the feature and treatment of cardiac metastasis through literature review and reporting of an unusual case. CASE: We reported a case of a 67 years-old man diagnosed as right ventricular metastasis from esophageal squamous cell with the help of echocardiography and pathological biopsy. Moreover, the patient survival period reached an astonishing 6 months, which far exceeded 4 weeks reported in previous literature. METHODS: We searched for relevant literature in the past decade on PUBMED and summarized the content of the literature to better clarify cardiac metastasis. CONCLUSION: Cardiac metastatic likely to occur in the elderly and in the right side of heart which related to hemodynamics. Surgical resection of metastatic tumors is the main treatment method, but patients usually die during the perioperative period due to its complexity and difficulty. Meanwhile, we have proposed some potentially effective treatment measures.

High expression of DNMT3A and DNMT3B regulatory factors of TGFB in non-neoplastic liver tissues of HCC.

Increased expression of TGFB regulatory factors DNMT3A and DNMT3B in non-neoplastic liver tissues of HCC patients is the goal of this study. Furthermore, we demonstrate that TGF- is capable of elevating the percentage of CD133+ cells present in liver cancer cell lines in a manner that is both consistent and long-lasting over several cell divisions. This process is linked to stable alterations in DNA methylation that occur over the whole of the genome and continue even after cell division. In addition, the silencing of de novo DNA methyl-transferases with siRNA is able to inhibit the phenotypic changes that are induced by TGF-. According to the findings of our research, there is a self-sustaining interaction between the DNA methylation machinery and the TGF- signaling pathway, which may be significant in the development of cellular phenotypes. CD133 positive and negative fractions expand within liver cancer cell lines in proportions that remain stable throughout time. In contrast to their CD133- counterparts, MACS-sorted CD133+ Huh7cells demonstrated the ability to shape themselves into spheres when grown under non-attachment circumstances. This study also found that the TGF- is responsible for the de novo induction of CD133, which is linked to an increase in the expression of DNMT3 genes and there is a correlation between the TGF-induced transition in the cell subpopulation and a distinct DNA methylome. TGF- has the potential to generate genome-wide alterations in DNA methylation, which ultimately leads to a persistent shift in the fraction of liver cancer cell subpopulations.

Species-Level Taxonomic Characterization of Uncultured Core Gut Microbiota of Plateau Pika.

Rarely has the vast diversity of bacteria on Earth been profiled, particularly on inaccessible plateaus. These uncultured microbes, which are also known as "microbial dark matter," may play crucial roles in maintaining the ecosystem and are linked to human health, regarding pathogenicity and prebioticity. The plateau pika (Ochotona curzoniae) is a small burrowing steppe lagomorph that is endemic to the Qinghai-Tibetan Plateau and is a keystone species in the maintenance of ecological balance. We used a combination of full-length 16S rRNA amplicon sequencing, shotgun metagenomics, and metabolomics to elucidate the species-level community structure and the metabolic potential of the gut microbiota of the plateau pika. Using a full-length 16S rRNA metataxonomic approach, we clustered 618 (166 ± 35 per sample) operational phylogenetic units (OPUs) from 105 plateau pika samples and assigned them to 215 known species, 226 potentially new species, and 177 higher hierarchical taxa. Notably, 39 abundant OPUs (over 60% total relative abundance) are found in over 90% of the samples, thereby representing a "core microbiota." They are all classified as novel microbial lineages, from the class to the species level. Using metagenomic reads, we independently assembled and binned 109 high-quality, species-level genome bins (SGBs). Then, a precise taxonomic assignment was performed to clarify the phylogenetic consistency of the SGBs and the 16S rRNA amplicons. Thus, the majority of the core microbes possess their genomes. SGBs belonging to the genus Treponema, the families Muribaculaceae, Lachnospiraceae, and Oscillospiraceae, and the order Eubacteriales are abundant in the metagenomic samples. In addition, multiple CAZymes are detected in these SGBs, indicating their efficient utilization of plant biomass. As the most widely connected metabolite with the core microbiota, tryptophan may relate to host environmental adaptation. Our investigation allows for a greater comprehension of the composition and functional capacity of the gut microbiota of the plateau pika. IMPORTANCE The great majority of microbial species remain uncultured, severely limiting their taxonomic characterization and biological understanding. The plateau pika (Ochotona curzoniae) is a small burrowing steppe lagomorph that is endemic to the Qinghai-Tibetan Plateau and is considered to be the keystone species in the maintenance of ecological stability. We comprehensively investigated the gut microbiota of the plateau pika via a multiomics endeavor. Combining full-length 16S rRNA metataxonomics, shotgun metagenomics, and metabolomics, we elucidated the species-level taxonomic assignment of the core uncultured intestinal microbiota of the plateau pika and revealed their correlation to host nutritional metabolism and adaptation. Our findings provide insights into the microbial diversity and biological significance of alpine animals.

Emergence of an ancient and pathogenic mammarenavirus.

Emerging zoonoses of wildlife origin caused by previously unknown agents are one of the most important challenges for human health. The Qinghai-Tibet Plateau represents a unique ecological niche with diverse wildlife that harbours several human pathogens and numerous previously uncharacterized pathogens. In this study, we identified and characterized a novel arenavirus (namely, plateau pika virus, PPV) from plateau pikas (Ochotona curzoniae) on the Qinghai-Tibet Plateau by virome analysis. Isolated PPV strains could replicate in several mammalian cells. We further investigated PPV pathogenesis using animal models. PPV administered via an intraventricular route caused trembling and sudden death in IFNαßR-/- mice, and pathological inflammatory lesions in brain tissue were observed. According to a retrospective serological survey in the geographical region where PPV was isolated, PPV-specific IgG antibodies were detected in 8 (2.4%) of 335 outpatients with available sera. Phylogenetic analyses revealed that this virus was clearly separated from previously reported New and Old World mammarenaviruses. Under the co-speciation framework, the estimated divergence time of PPV was 77-88 million years ago (MYA), earlier than that of OW and NW mammarenaviruses (26-34 MYA).

Comparative Evaluation of Standard RT-PCR Assays and Commercial Real-Time RT-PCR Kits for Detection of Lassa Virus.

Lassa virus (LASV) is a causative agent of hemorrhagic fever epidemic in West Africa. In recent years, it has been transmitted several times to North America, Europe, and Asia. Standard reverse transcription (RT)-PCR and real-time RT-PCR are extensively used for early detection of LASV. However, the high nucleotide diversity of LASV strains complicates the development of appropriate diagnostic assays. Here, we analyzed LASV diversity clustered with geographic location and evaluated the specificity and sensitivity of two standard RT-PCR methods (GPC RT-PCR/1994 and 2007) and four commercial real-time RT-PCR kits (namely, Da an, Mabsky, Bioperfectus, and ZJ) to detect six representative LASV lineages using in vitro synthesized RNA templates. The results showed that the GPC RT-PCR/2007 assay had better sensitivity compared to the GPC RT-PCR/1994 assay. The Mabsky and ZJ kits were able to detect all RNA templates of six LASV lineages. Contrastingly, the Bioperfectus and Da an kits failed to detect lineages IV and V/VI. The limit of detection for lineage I with the Da an, Bioperfectus, and ZJ kits were significantly higher than that of the Mabsky kit at an RNA concentration of 1 × 1010 to 1 × 1011 copies/mL. The Bioperfectus and Da an kits detected lineages II and III at an RNA concentration of 1 × 109 copies/mL, higher than that of the other kits. In conclusion, the GPC RT-PCR/2007 assay and the Mabsky kit were suitable assays for the detection of LASV strains based on good analytical sensitivity and specificity. IMPORTANCE Lassa virus (LASV) is a significant human pathogen causing hemorrhagic fever in West Africa. Increased traveling around the world raises the risk of imported cases to other countries. The high nucleotide diversity of LASV strains clustered with geographic location complicates the development of appropriate diagnostic assays. In this study, we showed that the GPC reverse transcription (RT)-PCR/2007 assay and the Mabsky kit are suitable for detecting most LASV strains. Future assays for molecular detection of LASV should be based on specific countries/regions along with new variants.

Discovery of a new class of reversible TEA domain transcription factor inhibitors with a novel binding mode.

The TEA domain (TEAD) transcription factor forms a transcription co-activation complex with the key downstream effector of the Hippo pathway, YAP/TAZ. TEAD-YAP controls the expression of Hippo-responsive genes involved in cell proliferation, development, and tumorigenesis. Hyperactivation of TEAD-YAP activities is observed in many human cancers and is associated with cancer cell proliferation, survival, and immune evasion. Therefore, targeting the TEAD-YAP complex has emerged as an attractive therapeutic approach. We previously reported that the mammalian TEAD transcription factors (TEAD1-4) possess auto-palmitoylation activities and contain an evolutionarily conserved palmitate-binding pocket (PBP), which allows small-molecule modulation. Since then, several reversible and irreversible inhibitors have been reported by binding to PBP. Here, we report a new class of TEAD inhibitors with a novel binding mode. Representative analog TM2 shows potent inhibition of TEAD auto-palmitoylation both in vitro and in cells. Surprisingly, the co-crystal structure of the human TEAD2 YAP-binding domain (YBD) in complex with TM2 reveals that TM2 adopts an unexpected binding mode by occupying not only the hydrophobic PBP, but also a new side binding pocket formed by hydrophilic residues. RNA-seq analysis shows that TM2 potently and specifically suppresses TEAD-YAP transcriptional activities. Consistently, TM2 exhibits strong antiproliferation effects as a single agent or in combination with a MEK inhibitor in YAP-dependent cancer cells. These findings establish TM2 as a promising small-molecule inhibitor against TEAD-YAP activities and provide new insights for designing novel TEAD inhibitors with enhanced selectivity and potency.

Is higher ambient temperature associated with acute appendicitis hospitalizations? A case-crossover study in Tongling, China.

Existing studies suggested that ambient temperature may affect the attack of acute appendicitis. However, the identification of the quantitative effect and vulnerable populations are still unknown. The purposes of this study were to quantify the impact of daily mean temperature on the hospitalization of acute appendicitis and clarify vulnerable groups, further guide targeted prevention of acute appendicitis in Tongling. Daily data of cases and meteorological factors were collected in Tongling, China, during 2015-2019. Time stratified case-crossover design and conditional logistic regression model were used to evaluate the odds ratio (OR) of ambient temperature on hospitalizations for acute appendicitis. Stratified analyses were performed by sex, age, and marital status. The odds ratio (OR) of hospitalizations for acute appendicitis increased by 1.6% for per 1 ℃ rise in mean temperature at lag3[OR = 1.016, 95% confidence interval (CI): 1.004-1.028]. In addition, our results suggest it is in the women that increased ambient temperature is more likely to contribute to acute appendicitis hospitalizations; we also found that the married are more susceptible to acute appendicitis hospitalizations due to increased ambient temperature than the unmarried; people in the 21-40 years old are more sensitive to ambient temperature than other age groups. The significant results of the differences between the subgroups indicate that the differences between the groups are all statistically significant. The elevated ambient temperatures increased the risk of hospitalizations for acute appendicitis. The females, married people, and patients aged 21-40 years old were more susceptible to ambient temperature. These findings suggest that more attention should be paid to the impact of high ambient temperature on acute appendicitis in the future.

RNA Virus Diversity in Birds and Small Mammals From Qinghai-Tibet Plateau of China.

Most emerging and re-emerging viruses causing infectious diseases in humans and domestic animals have originated from wildlife. However, current knowledge of the spectrum of RNA viruses in the Qinghai-Tibet Plateau in China is still limited. Here, we performed metatranscriptomic sequencing on fecal samples from 56 birds and 91 small mammals in Tibet and Qinghai Provinces, China, to delineate their viromes and focused on vertebrate RNA viruses. A total of 184 nearly complete genome RNA viruses belonging to 28 families were identified. Among these, 173 new viruses shared <90% amino acid identity with previously known viral sequences. Several of these viruses, such as those belonging to genera Orthonairovirus and Hepatovirus, could be zoonotic viruses. In addition, host taxonomy and geographical location of these viruses showed new hosts and distribution of several previously discovered viruses. Moreover, 12 invertebrate RNA viruses were identified with <40% amino acid identity to known viruses, indicating that they belong to potentially new taxa. The detection and characterization of RNA viruses from wildlife will broaden our knowledge of virus biodiversity and possible viral diseases in the Qinghai-Tibet Plateau.

Discovery and Evolution of a Divergent Coronavirus in the Plateau Pika From China That Extends the Host Range of Alphacoronaviruses.

Although plateau pikas are the keystone species in the plateau ecosystem of the Qinghai Province of China, little is known about their role in the evolution and transmission of viral pathogens, especially coronaviruses. Here, we describe the characterization and evolution of a novel alphacoronavirus, termed plateau pika coronavirus (PPCoV) P83, which has a prevalence of 4.5% in plateau pika fecal samples. In addition to classical gene order, the complete viral genome contains a unique nonstructural protein (NS2), several variable transcription regulatory sequences and a highly divergent spike protein. Phylogenetic analysis indicates that the newly discovered PPCoV falls into the genus Alphacoronavirus and is most closely related to rodent alphacoronaviruses. The co-speciation analysis shows that the phylogenetic trees of the alphacoronaviruses and their hosts are not always matched, suggesting inter-species transmission is common in alphacoronaviruses. And, PPCoV origin was estimated by molecular clock based on membrane and RNA-dependent RNA polymerase encoding genes, respectively, which revealed an apparent discrepancy with that of co-speciation analysis. PPCoV was detected mainly in intestinal samples, indicating a potential enteric tropism for the virus. Overall, this study extends the host range of alphacoronaviruses to a new order (Lagomorpha), indicating that plateau pikas may be the natural reservoir of PPCoV and play an important and long-term role in alphacoronavirus evolution.

Enorma shizhengliae sp. nov. and Eggerthella guodeyinii sp. nov., two new members of the family Coriobacteriaceae.

Four obligatory anaerobic, Gram-stain-positive, non-motile and rod-shaped organisms (HF-1365T, HF-1362, HF-1101T and HF-4214) were isolated from faecal samples of healthy Chinese subjects. Results of 16S rRNA gene sequence analyses showed that these isolates belong to the genera Enorma (strains HF-1365T and HF-1362) and Eggerthella (strains HF-1101T and HF-4214), closest to Enorma massiliensis (both 98.6 %) and Eggerthella sinensis (98.0 and 97.8 %), respectively. The whole genome sequences of strains HF-1365T and HF-1101T were 2.3 and 4.2 Mb in size with 61.7 and 66.2 mol% DNA G+C content, respectively. The average nucleotide identity and digital DNA-DNA hybridization values indicated that strains HF-1365T and HF-1101T represent novel species in the genera Enorma and Eggerthella. Major fatty acid constituents (>10 %) of strains HF-1365T and HF-1362 were C12 : 0 (24.7 and 23.9 %), C14 : 0 (21.9 and 20.6 %) and summed feature 1 (C15 : 1iso H/C13 : 0 3OH; 12.8 and 10.8 %); those of strains HF-1101T and HF-4214 were C18 : 1 ω9c (32.4 and 33.1 %) and C16 : 0 (13.9 and 14.0 %). Strain HF-1365T had phospholipid, glycolipid, lipid and phosphoglycolipid without any known quinones, while strain HF-1101T had diphosphatidylglycerol as the major polar lipid and MK-7 (80.7 %) as the predominant quinone. On the basis of their phylogenetic and phenotypic characteristics, strains HF-1365T and HF-1101T represent two distinct species, respectively, in the genera Enorma and Eggerthella, for which the names Enorma shizhengliae sp. nov. (type strain HF-1365T=CGMCC 1.17435T=GDMCC 1.1705T=JCM 33601T) and Eggerthella guodeyinii sp. nov. (type strain HF-1101T=CGMCC 1.17436T=GDMCC 1.1668T=JCM 33773T) are proposed.

Bacteroides luhongzhouii sp. nov. and Bacteroides zhangwenhongii sp. nov., isolated from human faeces.

Four unknown strains, characterized as Gram-stain-negative, strictly anaerobic, non-motile and rod-shaped, were isolated from fresh faeces of healthy humans in PR China. Pairwise sequence comparisons of the 16S rRNA genes showed that these isolates were separated into two clusters. Cluster I (strains HF-5141T and HF-106) was most closely related to Bacteroides xylanisolvens XB1AT (98.0-98.3 % similarity) and Bacteroides ovatus ATCC 8483T (97.3-97.5 %), whereas cluster II (strains HF-5287T and HF-5300) exhibited a similarity range of 96.8-97.0 % to Bacteroides finegoldii JCM 13345T, 96.7-96.9 % to Bacteroides faecis MAJ27T and 96.4-96.5 % to Bacteroides xylanisolvens XB1AT. The DNA G+C contents of type strains HF-5141T and HF-5287T were 41.5 and 42.6 mol%, respectively. These strains had anteiso-C15 : 0 as the major cellular fatty acid, MK-9 and MK-11 as the predominant respiratory quinones, and phosphatidylethanolamine, aminophospholipids and phospholipids as major polar lipids, which is typical for members of the genus Bacteroides. However, the average nucleotide identity and digital DNA-DNA hybridization values, accompanied by different phenotypic and biochemical characteristics, distinguished them from their corresponding closest relatives as well as from other recognized members of the genus Bacteroides. Therefore, strains HF-5141T and HF-5287T represent two novel species in the genus Bacteroides, for which the names Bacteroides luhongzhouii sp. nov. and Bacteroides zhangwenhongii sp. nov. are proposed, with HF-5141T (=CGMCC 1.16787T=GDMCC 1.1591T=JCM 33480T) and HF-5287T (=CGMCC 1.16724T=GDMCC 1.1590T=JCM 33481T) as type strains.

Cryo-EM structure of the Hippo signaling integrator human STRIPAK.

The striatin-interacting phosphatase and kinase (STRIPAK) complex is a large, multisubunit protein phosphatase 2A (PP2A) assembly that integrates diverse cellular signals in the Hippo pathway to regulate cell proliferation and survival. The architecture and assembly mechanism of this critical complex are poorly understood. Using cryo-EM, we determine the structure of the human STRIPAK core comprising PP2AA, PP2AC, STRN3, STRIP1, and MOB4 at 3.2-Å resolution. Unlike the canonical trimeric PP2A holoenzyme, STRIPAK contains four copies of STRN3 and one copy of each the PP2AA-C heterodimer, STRIP1, and MOB4. The STRN3 coiled-coil domains form an elongated homotetrameric scaffold that links the complex together. An inositol hexakisphosphate (IP6) is identified as a structural cofactor of STRIP1. Mutations of key residues at subunit interfaces disrupt the integrity of STRIPAK, causing aberrant Hippo pathway activation. Thus, STRIPAK is established as a noncanonical PP2A complex with four copies of regulatory STRN3 for enhanced signal integration.

Characterization and comparative study of the key odorants in Caoyuanwang mild-flavor style Baijiu using gas chromatography-olfactometry and sensory approaches.

Caoyuanwang Baijiu (CYW), a mild-flavor style Baijiu (MSB), is popular in northern China. However, there is a lack of studies reporting its aroma-active components. The aroma compounds of five CYW samples were analyzed using gas chromatography-olfactory-mass spectrometry coupled with aroma extraction dilution analysis. Fifty-five aroma-active compounds were identified in CYW, of which 27 had odor activity values ≥ 1. Reconstituted models successfully simulated the aroma profiles of CYW. The omission tests elucidated that ß-damascenone, dimethyl trisulfide, ethyl pentanoate, butanoic acid, ethyl acetate, 3-methylbutanal, ethyl lactate, hexanoic acid, γ-nonalactone, 3-hydroxy-2-butanone, ethyl butanoate, 1-propanol, 4-(ethoxymethyl)-2-methoxy-phenol, and vanillin were key odorants in CYW. The addition test confirmed the significant influence of dimethyl trisulfide on Chen-aroma note. Nine key odorants were identified as the differential quality-markers, and 85.71% key odorants were predicted using the partial least square regression (PLSR) analysis, indicating the applicability of PLSR in selecting the target compounds for omission tests.

Microbacterium caowuchunii sp. nov. and Microbacterium lushaniae sp. nov., isolated from plateau pika (Ochotona curzoniae) on the Qinghai-Tibet Plateau of PR China.

Four novel bacterial strains (ST-M6T, L-033, L-031T and Z-333) were isolated from the intestinal contents of plateau pikas (Ochotona curzoniae) collected on the Qinghai-Tibet Plateau, PR China. Cells were aerobic, non-motile, Gram-stain-positive, catalase-positive, oxidase-negative, capsuled and short-rod-shaped. Phylogenetic analyses based on the 16S rRNA gene sequences and 387 core genes indicated that the four isolates belong in the genus Microbacterium and clearly separate from recognized species. The two type strains (ST-M6T and L-031T) shared low 16S rRNA similarity, average nucleotide identity values and digital DNA-DNA hybridization relatedness with their phylogenetic neighbours (Microbacterium ginsengisoli DSM 18659T, Microbacterium hatanonis DSM 19179T, Microbacterium rhizomatis JCM 30598T, Microbacterium radiodurans CCTCC M208212T, Microbacterium oleivorans DSM 16091T and Microbacterium arborescens DSM 20754T). The genomic DNA G+C contents of strains ST-M6T and L-031T were 70.4 and 70.7 mol%, respectively. The major cellular fatty acids of strain ST-M6T were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0, in contrast to anteiso-C17 : 0, anteiso-C15 : 0 and anteiso-C17 : 1 ω9c of strain L-031T. Both type strains (ST-M6T and L-031T) were glycolate test positive and shared the following common features: MK-11 and MK-12 as major menaquinones; rhamnose, ribose, mannose and galactose as major cell-wall sugars; diphosphatidylglycerol, phosphatidylglycerol and two glycolipids as polar lipids; and ornithine, alanine, glycine and glutamic acid as cell-wall amino acids. Comparing the phenotypic, phylogenetic and chemotaxonomic features of the four strains and their related taxa, strains ST-M6T and L-031T represent two novel species of the genus Microbacterium, for which the names Microbacterium caowuchunii sp. nov. (type strain ST-M6T=CGMCC 1.16364T=DSM 104058T) and Microbacterium lushaniae sp. nov. (type strain L-031T =CGMCC 1.16363T=DSM 106170T) are proposed.

Boosting Vaccine-Elicited Respiratory Mucosal and Systemic COVID-19 Immunity in Mice With the Oral Lactobacillus plantarum.

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.

Beta- and Novel Delta-Coronaviruses Are Identified from Wild Animals in the Qinghai-Tibetan Plateau, China.

Outbreaks of severe virus infections with the potential to cause global pandemics are increasingly concerning. One type of those commonly emerging and re-emerging pathogens are coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2). Wild animals are hosts of different coronaviruses with the potential risk of cross-species transmission. However, little is known about the reservoir and host of coronaviruses in wild animals in Qinghai Province, where has the greatest biodiversity among the world's high-altitude regions. Here, from the next-generation sequencing data, we obtained a known beta-coronavirus (beta-CoV) genome and a novel delta-coronavirus (delta-CoV) genome from faecal samples of 29 marmots, 50 rats and 25 birds in Yushu Tibetan Autonomous Prefecture, Qinghai Province, China in July 2019. According to the phylogenetic analysis, the beta-CoV shared high nucleotide identity with Coronavirus HKU24. Although the novel delta-CoV (MtCoV) was closely related to Sparrow deltacoronavirus ISU42824, the protein spike of the novel delta-CoV showed highest amino acid identity to Sparrow coronavirus HKU17 (73.1%). Interestingly, our results identified a novel host (Montifringilla taczanowskii) for the novel delta-CoV and the potential cross-species transmission. The most recent common ancestor (tMRCA) of MtCoVs along with other closest members of the species of Coronavirus HKU15 was estimated to be 289 years ago. Thus, this study increases our understanding of the genetic diversity of beta-CoVs and delta-CoVs, and also provides a new perspective of the coronavirus hosts.