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Feline bocavirus (FBoV) is a globally distributed linear, single-stranded DNA virus infect cats, currently classified into three distinct genotypes. Although FBoV can lead to systemic infections, its complete pathogenic potential remains unclear. In this study, 289 blood samples were collected from healthy cats in Harbin, revealing an overall FBoV prevalence of 12.1%. Notably, genotypes 1 and 3 of FBoV were found co-circulating among the cat population in Harbin. Additionally, recombination events were detected, particularly in the newly discovered NG/104 and DL/102 strains. Furthermore, negative selection sites were predominantly observed across the protein coding genes of FBoV. These findings suggest a co-circulation of genetically diverse FBoV strains among cats in Harbin, indicate that purifying selection is the primary driving force shaping the genomic evolution of FBoV, and also underscore the importance of comprehensive surveillance efforts to enhance our understanding of the epidemiology and evolutionary characteristics of FBoV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Members of the genus Bocaparvovirus have a significant impact on human health and can infect a wide range of hosts, increasing the likelihood of crossing species barriers. Among the various mammalian hosts, rodents are widely recognized as important reservoirs for emerging and zoonotic viruses. However, despite recent reports of bocavirus infections in rodents, our current understanding of rat bocavirus (RBoV) genetic diversity and evolution is limited. In this study, rodent samples were collected from the urban areas of Guangzhou city, Southern China, to investigate the presence and genetic diversity of RBoV. Through PCR-based screening of 296 rodent spleens, 54 samples were determined to be positive for RBoV infection, and 12 nearly complete genome sequences of RBoV were recovered. Phylogenetic analysis revealed distinct lineages and sub-lineages of RBoV, and six recombination events with strong statistical support were identified, with five of these events involving sequences obtained from this study. These results highlight the genetic diversity of RBoV circulating in rodents in Guangzhou city and emphasize the importance of extensive surveillance to gain a better understanding of RBoV epidemiology, evolutionary characteristics, and potential for cross-species transmission., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Liver cancer, which is well-known to us as one of human most prevalent malignancies across the globe, poses a significant risk to live condition and life safety of individuals in every region of the planet. It has been shown that immune checkpoint treatment may enhance survival benefits and make a significant contribution to patient prognosis, which makes it a promising and popular therapeutic option for treating liver cancer at the current time. However, there are only a very few numbers of patients who can benefit from the treatment and there also exist adverse events such as toxic effects and so on, which is still required further research and discussion. Fortunately, the clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) provides a potential strategy for immunotherapy and immune checkpoint therapy of liver cancer. In this review, we focus on elucidating the fundamentals of the recently developed CRISPR/Cas9 technology as well as the present-day landscape of immune checkpoint treatment which pertains to liver cancer. What's more, we aim to explore the molecular mechanism of immune checkpoint treatment in liver cancer based on CRISPR/Cas9 technology. At last, its encouraging and powerful potential in the future application of the clinic is discussed, along with the issues that already exist and the difficulties that must be overcome. To sum up, our ultimate goal is to create a fresh knowledge that we can utilize this new CRISPR/Cas9 technology for the current popular immune checkpoint therapy to overcome the treatment issues of liver cancer., (© 2024 IOP Publishing Ltd.)

Combination immunotherapy has shown promising potential for enhancing the objective response rate compared to immune checkpoint blockade (ICB) monotherapy. However, combination therapy with multi-drugs is limited by the different properties of the agents and inconsistent synergistic targeted delivery. Herein, based on a universal triterpene template and the anticancer active agent ursolic acid (UA), a cytomembrane-coated biomimetic delivery nanoplatform (UR@M) prepared by the self-assembly of a PD-L1 targeted CRISPR/Cas9 system and UA was designed for hepatocellular carcinoma (HCC) treatment. UR@M showed enhanced tumor accumulation in vivo with homologous tumor targeting, and CRISPR in the nanosystem exhibited potent gene-editing efficiency of 76.53% in vitro and 62.42% in vivo with no off-target effects. UA activated the natural immune system through the TLR-2-MyD88-TRAF6 pathway, which synergistically enhanced the proliferation of natural killer cells and dendritic cells and realized excellent immune cytotoxic T cell infiltration by combining with the ICB of PD-L1 . The strategy of work along both lines based on innate immune and adaptive immunity displayed a significant effect in tumor regression. Overall, the UA-templated strategy "killed three birds with one stone" by establishing a self-assembly nanosystem, inducing tumor cell death, and promoting synergistic immunostimulation for HCC treatment., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors.)

As a sort of fluorescent carbon nanomaterial with a particle size of less than 10 nm, carbon dots (CDs) have their own merits of good dispersibility in water, stable optical properties, strong chemical inertness, stable optical properties, and good biosecurity. These excellent peculiarities facilitated them like sensing, imaging, medicine, catalysis, and optoelectronics, making them a new star in the field of nanotechnology. In particular, the development of CDs in the fields of chemical probes, imaging, cancer therapy, antibacterial and drug delivery has become a hot topic in current research. Although the biomedical applications in CDs have been demonstrated in many research articles, a systematic summary of their role in biomedical applications is scarce. In this review, we introduced the basic information of CDs in detail, including synthesis approaches of CDs as well as their favorable properties including photoluminescence and low cytotoxicity. Subsequently, the application of CDs in the field of biomedicine was emphasized. Finally, the main challenges and research prospects of CDs in this field were proposed, which might provide some detailed information in designing new CDs in this promising biomedical field., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Influenza A virus (IAV) is a highly contagious pathogen causing dreadful losses to humans and animals around the globe. As is known, immune escape is a strategy that benefits the proliferation of IAVs by antagonizing, blocking, and suppressing immune surveillance. The HA protein binds to the sialic acid (SA) receptor to enter the cytoplasm and initiate viral infection. The conserved components of the viral genome produced during replication, known as the pathogen-associated molecular patterns (PAMPs), are thought to be critical factors for the activation of effective innate immunity by triggering dependent signaling pathways after recognition by pattern recognition receptors (PRRs), followed by a cascade of adaptive immunity. Viral infection-induced immune responses establish an antiviral state in the host to effectively inhibit virus replication and enhance viral clearance. However, IAV has evolved multiple mechanisms that allow it to synthesize and transport viral components by "playing games" with the host. At its heart, this review will describe how host and viral factors interact to facilitate the viral evasion of host immune responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Su, Chen, Li and Shao.)

The genus Hepacivirus comprises a diverse range of genetically distinct viruses that infect both mammalian and non-mammalian hosts, with some posing significant risks to human and animal health. Members of the genus Hepacivirus are typically classified into fourteen species ( Hepacivirus A-N ), with ongoing discoveries of novel hepaciviruses like Hepacivirus P and Hepacivirus Q . In this study, a novel Hepacivirus was identified in duck liver samples collected from live poultry markets in Hunan province, China, using unbiased high-throughput sequencing and meta-transcriptomic analysis. Through sequence comparison and phylogenetic analysis, it was determined that this newly discovered Hepacivirus belongs to a new subspecies of Hepacivirus Q . Moreover, molecular screening revealed the widespread circulation of this novel virus among duck populations in various regions of Hunan province, with an overall prevalence of 13.3%. These findings significantly enhence our understanding of the genetic diversity and evolution of hepaciviruses, emphasizing the presence of genetically diverse hepaciviruses duck populations in China. Given the broad geographical distribution and relatively high positive rate, further investigations are essential to explore any potential associations between Hepacivirus Q and duck-related diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Chen, Wu, Yi and Shao.)

The heterogeneity of hepatocellular carcinoma (HCC) and the complexity of the tumor microenvironment (TME) pose challenges to efficient drug delivery and the antitumor efficacy of combined or synergistic therapies. Herein, a metal-coordinated carrier-free nanodrug (named as USFe 3+ LA NPs) was developed for ferroptosis-mediated multimodal synergistic anti-HCC. Natural product ursolic acid (UA) was incorporated to enhance the sensitivity of tumor cells to sorafenib (SRF). Surface decoration of cell penetration peptide and epithelial cell adhesion molecule aptamer facilitated the uptake of USFe 3+ LA NPs by HepG2 cells. Meanwhile, Fe 3+ ions could react with intracellular hydrogen peroxide, generating toxic hydroxyl radical (·OH) for chemodynamical therapy (CDT) and amplified ferroptosis by cystine/glutamate antiporter system (System X c - ), which promoted the consumption of glutathione (GSH) and inhibited the expression of glutathione peroxidase 4 (GPX4). Notably, these all-in-one nanodrugs could inhibit tumor metastasis and induced immunogenic cell death (ICD). Last but not least, the nanodrugs demonstrated favorable biocompatibility, augmenting the immune response against the programmed death-ligand 1 (PD-L1) by increasing cytotoxic T cell infiltration. In vivo studies revealed significant suppression of tumor growth and distant metastasis. Overall, our work introduced a novel strategy for applications of metal-coordinated co-assembled carrier-free nano-delivery system in HCC combination therapy, especially in the realms of cancer metastasis prevention and immunotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The effectiveness of chemotherapeutic agents for hepatocellular carcinoma (HCC) is unsatisfactory because of tumor heterogeneity, multidrug resistance, and poor target accumulation. Therefore, multimodality-treatment with accurate drug delivery has become increasingly popular. Herein, a cell penetrating peptide-aptamer dual modified-nanocomposite (USILA NPs) was successfully constructed by coating a cell penetrating peptide and aptamer onto the surface of sorafenib (Sora), ursolic acid (UA) and indocyanine green (ICG) condensed nanodrug (USI NPs) via one-pot assembly for targeted and synergistic HCC treatment. USILA NPs showed higher cellular uptake and cytotoxicity in HepG2 and H22 cells, with a high expression of epithelial cell adhesion molecule (EpCAM). Furthermore, these NPs caused more significant mitochondrial membrane potential reduction and cell apoptosis. These NPs could selectively accumulate at the tumor site of H22 tumor-bearing mice and were detected with the help of ICG fluorescence; moreover, they retarded tumor growth better than monotherapy. Thus, USILA NPs can realize the targeted delivery of dual drugs and the integration of diagnosis and treatment. Moreover, the effects were more significant after co-administration of iRGD peptide, a tumor-penetrating peptide with better penetration promoting ability or programmed cell death ligand 1 (PD-L1) antibody for the reversal of the immunosuppressive state in the tumor microenvironment. The tumor inhibition rates of USILA NPs + iRGD peptide or USILA NPs + PD-L1 antibody with good therapeutic safety were 72.38 % and 67.91 % compared with control, respectively. Overall, this composite nanosystem could act as a promising targeted tool and provide an effective intervention strategy for enhanced HCC synergistic treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Q fever is a significant zoonotic disease caused by Coxiella burnetii, an obligate intracellular gram-negative bacterium. Although C. burnetii infection has been identified in various animal species, domestic ruminants serve as the primary reservoirs and main sources of human infection. Understanding of the epidemiology of C. burnetii in domestic ruminants is crucial for preventing and controlling of C. burnetii infection in humans. In this study, spleen tissues from sheep and goats were collected in Hennan province, China. Through PCR screening, C. burnetii was detected in sheep and goats in Henan province with an overall infection rate of 6.8 %. Sequence comparison and phylogenetic analysis revealed that all newly identified C. burnetii strains shared a close genetic relationship with those found in humans worldwide. These findings highlight the high risk of C. burnetii infection among slaughterhouse workers and emphasize the importance of epidemiological studies that investigate samples from both humans and animals within the "One Health" framework. Such surveillance will contribute to a better understanding of the epidemic situation and aid in the development of effective prevention and control strategies for C. burnetii infections in humans., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Both ursolic acid (UA) and sorafenib (Sora) have been generally utilized in cancer treatment, and the combination of the two has also shown a good anti-tumor effect. However, single-agent therapy for Hepatocellular carcinoma (HCC) has the disadvantages of multi-drug resistance, poor water solubility and low bioavailability, and the application of traditional nanocarrier materials is limited due to their low drug loading and low carrier-related toxicity. Therefore, we prepared US NPs with different proportions of UA and Sora by solvent exchange method for achieving synergistic HCC therapy. US NPs had suitable particle size, good dispersibility and storage stability, which synergistically inhibited the proliferation of HepG2 cells, SMMC7721 cells and H22 cells. In addition, we also proved that US NPs were able to suppress the migration of HepG2 cells and SMMC7721 cells and reduce the adhesion ability and colony formation ability of these cells. According to the results, US NPs could degrade the membrane potential of mitochondrial, participate in cell apoptosis, and synergistically induce autophagy. Collectively, the carrier-free US NPs provide new strategies for HCC treatment and new ideas for the development of novel nano-drug delivery systems containing UA and Sora., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Tumor microenvironment (TME) stimuli-responsive nanoassemblies are emerging as promising drug delivery systems (DDSs), which acquire controlled release by structural transformation under exogenous stimulation. However, the design of smart stimuli-responsive nanoplatforms integrated with nanomaterials to achieve complete tumor ablation remains challenging. Therefore, it is of utmost importance to develop TME-based stimuli-responsive DDSs to enhance drug-targeted delivery and release at tumor sites. Herein, we proposed an appealing strategy to construct fluorescence-mediated TME stimulus-responsive nanoplatforms for synergistic cancer therapy by assembling photosensitizers (PSs) carbon dots (CDs), chemotherapeutic agent ursolic acid (UA), and copper ions (Cu 2+ ). First, UA nanoparticles (UA NPs) were prepared by self-assembly of UA, then UA NPs were assembled with CDs via hydrogen bonding force to obtain UC NPs. After combining with Cu 2+ , the resulting particles (named UCCu 2+ NPs) exhibited quenched fluorescence and photosensitization due to the aggregation of UC NPs. Upon entering the tumor tissue, the photodynamic therapy (PDT) and the fluorescence function of UCCu 2+ were recovered in response to TME stimulation. The introduction of Cu 2+ triggered the charge reversal of UCCu 2+ NPs, thereby promoting lysosomal escape. Furthermore, Cu 2+ resulted in additional chemodynamic therapy (CDT) capacity by reacting with hydrogen peroxide (H 2 O 2 ) as well as by consuming glutathione (GSH) in cancer cells through a redox reaction, hence magnifying intracellular oxidative stress and enhancing the therapeutic efficacy due to reactive oxygen species (ROS) therapy. In summary, UCCu 2+ NPs provided an unprecedented novel approach for improving the therapeutic efficacy through the three-pronged (chemotherapy, phototherapy, and heat-reinforced CDT) attacks to achieve synergistic therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Thrombus is one of the culprits for global health problems. However, most current antithrombotic drugs are limited by restricted targeting ability and a high risk of systemic bleeding. A hybrid cell membrane-coated biomimetic nanosystem (PM/RM@PLGA@P/R) was constructed in this paper to fulfil the targeted delivery of ginsenoside (Rg1) and perfluorohexane (PFH). Poly lactic-co-glycolic acid (PLGA) is used as carriers to coat Rg1 and PFH. Thanks to the camouflage of erythrocyte membrane (RM) and platelet membrane (PM), the nanosystem in question possesses remarkable features including immune escape and self-targeting. Therefore, a compact nano-core with PLGA@P/R was formed, with a hybrid membrane covering the surface of the core, forming a "core-shell" structure. With its "core-shell" structure, this nanoparticle fancifully combines the advantages of both PFH (the low-intensity focused ultrasound (LIFU)-responsive phase-change thrombolysis) and Rg1(the antioxidant, anti-inflammatory and anticoagulant abilities). Meanwhile, PM/RM@PLGA@P/R nanoparticles exhibits superior in-vitro performance in terms of ROS scavenging, anticoagulant activity and immune escape compared with those without cell membranes (PLGA@P/R). Furthermore, in the animal experiment in which the tail vein thrombosis model was established by injecting k-carrageenan, the combined treatment of LIFU and PM/RM@PLGA@P/R showed a satisfactory antithrombotic efficiency (88.20 %) and a relatively higher biological safety level. This strategy provides new insights into the development of more effective and safer targeted biomimetic nanomedicines for antithrombotic treatments, possessing potential application in synergistic therapy field., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2023. Published by Elsevier B.V.)

Canine circovirus (CanineCV) is a single-stranded DNA virus that circulates in dogs and wild carnivores around the world. It has been suggested to be associated with diseases of respiratory and gastrointestinal systems, though its pathogenic potential remains unclear. Currently, CanineCV is divided into six genotypes (genotype 1-6), and genotypes 2, 3, and 4 have been described in China. In this study, 359 blood samples from pet dogs with or without clinical signs were collected in Harbin city. After PCR screening, a total of 34 samples were tested positive for CanineCV, and nine full-length genome sequences were recovered from positive samples. Pairwise sequence comparison showed that they shared 82.4-99.3% genome-wide identity with other CanineCVs available in GenBank. Additionally, recombination events were detected, all of which were determined to be associated with sequences obtained in China. The reconstructed phylogenetic tree based on the recombination-free complete genome sequences revealed that the complete genome sequences generated herein were clustered into genotypes 1 and 3. Furthermore, purifying selection was the dominant evolutionary pressure acting on the genomes of CanineCV. These results expand the knowledge about the genetic diversity of CanineCV circulating in China, and also promote us to better understand the evolution of CanineCV., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

CRISPR/Cas9 genome editing is a promising therapeutic technique, which makes precise and rapid gene editing technology possible on account of its high sensitivity and efficiency. CRISPR/Cas9 system has been proved to able to effectively disrupt and modify genes, which shows great potential for cancer treatment. Current researches proves that virus vectors are capable of effectively delivering the CRISPR/Cas9 system, but immunogenicity and carcinogenicity caused by virus transmission still trigger serious consequences. Therefore, the greatest challenge of CRISPR/Cas9 for cancer therapy lies on how to deliver it to the target tumor site safely and effectively. Non-viral delivery systems with specific targeting, high loading capacity, and low immune toxicity are more suitable than viral vectors, which limited by uncontrollable side effects. Their medical advances and applications have been widely concerned. Herein, we present the molecule mechanism and different construction strategies of CRISPR/Cas9 system for editing genes at the beginning of this research. Subsequently, several common CRISPR/Cas9 non-viral deliveries for cancer treatment are introduced. Lastly, based on the main factors limiting the delivery efficiency of non-viral vectors proposed in the existing researches and literature, we summarize and discuss the main methods to solve these limitations in the existing tumor treatment system, aiming to introduce further optimization and innovation of the CRISPR/Cas9 non-viral delivery system suitable for cancer treatment., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Hantaviridae currently encompasses seven genera and 53 species. Multiple hantaviruses such as Hantaan virus, Seoul virus, Dobrava-Belgrade virus, Puumala virus, Andes virus, and Sin Nombre virus are highly pathogenic to humans. They cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome or hantavirus pulmonary syndrome (HCPS/HPS) in many countries. Some hantaviruses infect wild or domestic animals without causing severe symptoms. Rodents, shrews, and bats are reservoirs of various mammalian hantaviruses. Recent years have witnessed significant advancements in the study of hantaviruses including genomics, taxonomy, evolution, replication, transmission, pathogenicity, control, and patient treatment. Additionally, new hantaviruses infecting bats, rodents, shrews, amphibians, and fish have been identified. This review compiles these advancements to aid researchers and the public in better recognizing this zoonotic virus family with global public health significance.

Ticks play an important role in the evolution and transmission of Anaplasmataceae bacteria which are agents of emerging infectious diseases. In this study, a total of 1286 adult ticks belonging to five species were collected from cattle, goats, horses and vegetation in Harbin area, Heilongjiang province, northeastern China. The tick-borne Anaplasmataceae bacteria were identified by amplifying and sequencing the 16S rRNA (rrs) and heat shock protein-60 encoding (groEL) genes. The results showed that Ixodes persulcatus was dominant (38.8%, 499/1283) among the five tick species, and Anaplasmataceae bacteria were detected in all tick species with an overall prevalence of 7.4%. Four species of Anaplasmataceae bacteria (Anaplasma phagocytophilum, Anaplasma ovis, Anaplasma bovis, and "Candidatus Neoehrlichia mikurensis"), which are pathogenic to humans and/or animals, were identified from tick samples by phylogenetic analyzes of the rrs and groEL gene sequences. Interestingly, the cluster 1 strains were first identified in Asian, and a novel cluster was also detected in this study. These data revealed the genetic diversity of Anaplasmataceae bacteria circulating in ticks in Harbin area, highlighting the need to investigate these tick-borne pathogens and their risks to human and animal health., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier GmbH.)

Understanding the evolutionary history of endangered species is crucial for identifying the main reasons for species endangerment in the past and predicting the changing trends and evolutionary directions of their future distribution. In order to study the impact of environmental changes caused by deep valley incision after the uplift of the Qinghai-Tibet Plateau on endangered species, we collected 23 samples belonging to four populations of Aleuritopteris grevilleoides , an endangered fern endemic to the dry-hot valleys (DHV) of Yunnan. Single-nucleotide variation sites (SNPs) were obtained by the genotyping-by-sequencing (GBS) method, and approximately 8085 SNP loci were identified. Through the reconstruction and analysis of genetic diversity, population structure, population dynamics, evolution time, and ancestral geographical distribution, combined with geological historical events such as the formation of dry-hot valleys, this study explores the formation history, current situation, reasons for endangerment and scientifically sound measures for the protection of A. grevilleoides . In our study, A. grevilleoides had low genetic diversity (Obs_Het = 0.16, Exp_Het = 0.32, Pi = 0.33) and a high inbreeding coefficient (Fis = 0.45). The differentiation events were 0.18 Mya, 0.16 Mya, and 0.11 Mya in the A. grevilleoides and may have been related to the formation of terraces within the dry-hot valleys. The history of population dynamics results shows that the diversion of the river resulted in a small amount of gene flow between the two clades, accompanied by a rapid increase in the population at 0.8 Mya. After that, the effective population sizes of A. grevilleoides began to contract continuously due to topographic changes resulting from the continuous expansion of dry-hot valleys. In conclusion, we found that the environmental changes caused by geological events might be the main reason for the changing population size of A. grevilleoides .

Bovine hepacivirus (BovHepV) is a member of the genus Hepacivirus of the family Flaviviridae , which can cause acute or persistent infections in cattle. Currently, BovHepV strains identified in cattle populations worldwide can be classified into two genotypes with eight subtypes in genotype 1. BovHepV has been identified in a wide geographic area in China. Interestingly, the viral RNA of BovHepV has also been detected in ticks in Guangdong province, China. In this study, Rhipicephalus microplus tick samples were collected in Heilongjiang province, northeastern China, and BovHepV was screened with an overall positive rate of 10.9%. Sequence comparison and phylogenetic analysis showed that the BovHepV strains detected in this study belong to the subtype G. This is the first report about the detection of BovHepV in ticks in Heilongjiang province, China, which expands our knowledge that ticks may be a transmission vector of BovHepV., Competing Interests: SK was employed by the company Beijing Biomedical Technology Center of Jofunhwa Biotechnology (Nanjing) Co., Ltd., China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yuan, Yao, Lian, Kong, Shao and Zhang.)

Introduction: To devise a precise and efficient tool for predicting the individualized risk of acute-phase response (APR) in bisphosphonate (BP)-naive osteoporotic (OP) patients, receiving their first intravenous dose of zoledronate (ZOL)., Methods: The baseline clinical and laboratory data of 475 consecutive BP-naive OP patients, who received their first intravenous dose of ZOL between March 2016 and March 2021 in the Affiliated Kunshan Hospital of Jiangsu University, were chosen for analysis. Univariate and multivariable logistic regression models were generated to establish candidate predictors of APR fever risk, using three distinct fever thresholds, namely, 37.3 °C (model A), 38.0 °C (model B), and 38.5 °C (model C). Next, using predictor regression coefficients, three fever-threshold nomograms were developed. Discrimination, calibration, and clinical usefulness of each predicting models were then assessed using the area under the curve (AUC), calibration curve (CC), and decision curve analysis (DCA). The internal and external model validations were then performed., Results: The stable predictors were age, serum 25-hydroxy vitamin D, serum total calcium, and peripheral blood erythrocytes count. These were negatively associated with the APR fever risk. The AUCs of models A, B, and C were 0.828 (95% confidence intervals [CI], 0.782 to 0.874), 0.825 (95% CI, 0.767 to 0.883), and 0.879 (95% CI, 0.824 to 0.934), respectively. Good agreement was observed between the predictions and observations in the CCs of all three nomograms., Conclusions: This study developed and validated nomogram prediction models that can predict APR fever risk in BP-naive OP patients receiving their first infusion of ZOL., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Conventional treatments for cancer, such as chemotherapy, surgical resection, and radiotherapy, have shown limited therapeutic efficacy, with severe side effects, lack of targeting and drug resistance for monotherapies, which limit their clinical application. Therefore, combinatorial strategies have been widely investigated in the battle against cancer. Herein, we fabricated a dual-targeted nanoscale drug delivery system based on EpCAM aptamer- and lactic acid-modified low-polyamidoamine dendrimers to co-deliver the FDA-approved agent disulfiram and photosensitizer indocyanine green, combining the imaging and therapeutic functions in a single platform. The multifunctional nanoparticles with uniform size had high drug-loading payload, sustained release, as well as excellent photothermal conversion. The integrated nanoplatform showed a superior synergistic effect in vitro and possessed precise spatial delivery to HepG2 cells with the dual-targeting nanocarrier. Intriguingly, a robust anticancer response of chemo-phototherapy was achieved; chemotherapy combined with the efficacy of phototherapy to cause cellular apoptosis of HepG2 cells (>35%) and inhibit the regrowth of damaged cells. Furthermore, the theranostic nanosystem displayed fluorescence imaging in vivo , attributed to its splendid accumulation in the tumor site, and it provided exceptional tumor inhibition rate against liver cancer cells (>76%). Overall, our research presents a promising multifunctional theranostic nanoplatform for the development of synergistic therapeutics for tumors in further applications.

Lycorisinsularis S.Y.Zhang & J.W.Shao, a new fertile diploid species from coastal provinces in eastern China is described. This new species is most similar to L.sprengeri in morphology and has been misidentified as the latter for a long time. However, it can be distinguished from the latter by the relatively longer perianth tube (1.5‒2.5 cm vs. less than 1.3 cm), a characteristic that was overlooked before. Phylogenetic analysis, based on complete plastid genome, showed that L.insularis is not genetically related to L.sprengeri in the genus. The former was a sister group of L.sanguinea , while the latter was closely related to L.longituba and L.chinensis and they were respectively located on different clades that were separated at the base of the phylogenetic tree. The chromosome number of L.insularis is 2n = 22. At present, as the new species is relatively widely distributed and the wild population can normally reproduce by seeds, we evaluate it as LC (Least Concern) according to criteria of the IUCN Red List., (Si-Yu Zhang, Hao-Tian Wang, Ying-Feng Hu, Wei Zhang, Song Hu, Jian-Wen Shao.)

The increasing prevalence and transmission of tick-borne diseases, especially those emerging ones, have posed a significant threat to public health. Thus, the discovery of neglected pathogenic agents carried and transmitted by ticks is urgently needed. Using unbiased high-throughput sequencing, a novel Orthonairovirus designated as Meihua Mountain virus (MHMV), was identified in bloodsucking ticks collected from cattle and wild boars in Fujian province, Southeastern China. The full-length genome was determined by RT-PCR and RACE. Genomic architecture of MHMV shares typical features with orthonairoviruses. Phylogenetic analyses suggested that MHMV is clustered into the Nairobi sheep disease (NSD) genogroup of the genus Orthonairovirus and is closely related to the Hazara virus. The RdRp, GPC, and N protein of MHMV shares 62.3%-83.5%, 37.1%-66.1%, and 53.4%-77.3% amino acid identity with other NSD genogroup viruses, respectively, representing a novel species. The overall pooled prevalence of MHMV in ticks was 2.53% (95% CI: 1.62%-3.73%, 22 positives of 134 tick pools), with 7.38% (95% CI: 3.84%-12.59%, 11 positives of 18 pools) in Haemaphysalis hystricis , 6.02% (95% CI: 1.85%-14.22%, four positives of eight pools) in H. formosensis , 25.03% (95% CI: 9.23%-54.59%, six positive of eight pools) in Dermacentor taiwanensis , and 0.16% (95% CI: 0.01%-0.72%, one positive of 100 pools) in Rhipicephalus microplus . This study presented the first report of tick-carried Orthonairovirus in Fujian province and highlighted the broad geographic distribution and high genetic diversity of orthonairoviruses in China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Li, Shao, Pei, Cao, Huang and Sun.)

Background: The aims of this study were to evaluate the levels of preretinal oxygen tension in patients with diabetes who did not have hypertension by using three-dimensional spoiled gradient-recalled (3D-SPGR) echo sequence imaging and to explore the correlation between diabetic retinopathy (DR) and changes in preretinal oxygen tension., Method: This study involved 15 patients with type 2 diabetes without hypertension, who were divided into a diabetic retinopathy (DR) group (n = 10 eyes) and a diabetic non-retinopathy (NDR) group (n = 20 eyes), according to the results of a fundus photography test. Another healthy control group (n = 14 eyes) also participated in the study. The preretinal vitreous optic disc area, nasal side, and temporal side signal intensity of the eyes was assessed before and after oxygen inhalation with the use of 3D-SPGR echo magnetic resonance imaging (MRI). The signal acquisition time was 10, 20, 30, 40, and 50 min after oxygen inhalation., Results: The results showed that, in the DR and NDR groups, the preretinal vitreous oxygen tension increased rapidly at 10 min after oxygen inhalation and peaked at 30-40 min, and the increased slope of the DR group was higher than that of the NDR group. The oxygen tension of the preretinal vitreous gradually increased after oxygen inhalation, and the difference between the DR and NDR groups and the control group was statistically significant (P < 0.05). The preretinal vitreous oxygen tension was higher in the optic disc, temporal side, and nasal side in the NDR group than in the control group, and the difference was statistically significant (P < 0.05). The maximum slope ratios of the optic disc and the temporal side of the DR group were greater than those of the control group, and the difference was statistically significant (P < 0.05)., Conclusion: Three-dimensional-SPGR echo MRI sequencing technology is useful for detecting preretinal oxygen tension levels in patients with diabetes. It can be used as one of the functional and imaging observation indicators for the early diagnosis of DR., (© 2022. The Author(s).)

Bartonella spp. are gram-negative bacteria that can infect a wide spectrum of mammals. Rodents are considered to be the natural reservoir of many Bartonella species that are transmitted by various blood-sucking arthropods. The close contact between rodents and humans in urban areas increased the chance of transmitting rodent-borne Bartonella to humans. Investigation of the epidemiological characteristics of Bartonella infection in rodents is of great significance for the prevention and control of human Bartonellosis. In this study, rodents were captured to monitor the prevalence of Bartonella in urban areas of Guangzhou city. Six official or candidate species of Bartonella , including two confirmed zoonotic species, were detected with an overall prevalence of 6.4% in rodents captured herein. In addition, Rattus norvegicus was the predominant host species for Bartonella infection, and B. queenslandensis was the dominant species circulating in rodents in these areas. These results provide insights into the prevalence and genetic diversity of Bartonella species circulating in rodents in the urban areas of Guangzhou, and also urged the surveillance of rodent-associated Bartonella species in these areas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yao, Liu, Sun, Zhang, Lv, Zhang and Shao.)

Based on the complete chloroplast genome, morphology, and karyotype evidence, we identified a new nothospecies, Lycoris × jinzheniae S.Y. Zhang, P.C. Zhang & J.W. Shao, in eastern China. This new nothospecies has been inappropriately named Lycoris × albiflora in the previous literature for more than 30 years. However, the new nothospecies resulted from the hybridization of L. sprengeri and L. chinensis and had the following characteristics: the karyotype was 2n = 19 = 3V + 16I, the leaves emerged in the spring, the ratio of filament to corolla length was approximately 1.2, tepals were slightly undulated and curved, and it was distributed throughout eastern China. These characteristics are quite different from those of L. × albiflora ; thus, in this study, we named it and provided a detailed morphological description and diagnosis.

Primulaxinningensis Wei Zhang bis & J.W.Shao, a new species from Hunan Province, China, is described. Its leaf morphology is similar to the P.merrilliana complex and flower morphology similar to P.cicutariifolia , but it can be distinguished from the former by the black pollen sac, corolla lobes apex obviously emarginate and can be differed from the latter by cotyledon triangular obovate, plants densely covered with glandular hairs and special habitat (karst caves). The whole plastid genome of this new species is 151, 601-151, 630 bp in length. Based on the whole plastid genome sequences, phylogenetic trees revealed that the new species did not genetically relate to the above two mentioned morphologically similar species, but it was closely related to P.hubeiensis . Currently, only three populations were discovered within a small distribution area, thus, it is preliminarily considered as Vulnerable (VU) according to criteria of the IUCN Red List., (Wei Zhang, Yu Zhang, Jian Wen Shao.)

The newly established virus family Phenuiviridae in Bunyavirales harbors viruses infecting three kingdoms of host organisms (animals, plants, and fungi), which is rare in known virus families. Many phenuiviruses are arboviruses and replicate in two distinct hosts (e.g., insects and humans or rice). Multiple phenuivirid species, such as Dabie bandavirus, Rift Valley fever phlebovirus, and Rice stripe tenuivirus, are highly pathogenic to humans, animals, or plants. They impose heavy global burdens on human health, livestock industry, and agriculture and are research hotspots. In recent years the taxonomy of Phenuiviridae has been expanded greatly, and research on phenuiviruses has made significant progress. With these advances, this review drew a novel panorama regarding the biomedical significance, distribution, morphology, genomics, taxonomy, evolution, replication, transmission, pathogenesis, and control of phenuiviruses, to aid researchers in various fields to recognize this highly adaptive and important virus family and conduct relevant risk analysis., (© 2022 Wiley Periodicals LLC.)

Leptospirosis is a neglected zoonotic disease with global importance caused by pathogenic Leptospira . Rodents are considered the most significant reservoirs for both human and animal infection. Historically, Guangzhou has been an endemic region of human leptospirosis. Although the incidence in humans has significantly decreased in the past decades in China, the epidemiology of pathogenic Leptospira in wild rodents is of great significance for the prevention and control of human leptospirosis. In this study, a total of 296 wild rodents were trapped in urban areas of Guangzhou, in southern China, in 2020. Three pathogenic Leptospira species, i.e., Leptospira interrogans , L. borgpetersenii , and L. kirschneri , were detected by nested PCR in this wild rodent population with an overall prevalence of 9.5%. Additionally, L. interrogans was detected in three of the four captured rodent species, and the relative high prevalence suggests that L. interrogans probably represents the preponderant species of the pathogenic Leptospira circulating in Guangzhou. Taken together, this study reveals a high genetic diversity of pathogenic Leptospira disseminated among wild rodents in the urban areas of Guangzhou and emphasizes that the risk for the occurrence of human leptospirosis in Guangzhou remains high.

Objective: To investigate the correlation between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and the pathological classification of idiopathic orbital inflammatory pseudotumors (IOIPs)., Methods: Nineteen patients who were diagnosed with IOIPs (a total of 24 affected eyes) between November 2018 and December 2020 were included in the study. All the patients underwent magnetic resonance imaging orbital plain scans and IVIM-DWI multiparameter scans before an operation. The true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) values were obtained. Based on histopathology, the lesions were divided into three types: lymphocytic infiltration, fibrosclerotic, and mixed. The correlation between IVIM-DWI parameters and pathological classification was tested with the histopathological results as the gold standard. The data were analyzed using SPSS version 17.0, with P < 0.05 defined as significant., Results: Among the 19 patients (24 eyes) affected by IOIP, there were no significant differences between IOIP pathological classification and gender or age (P > 0.05). There were statistically significant differences between the D and f values for different pathological types of IOIP and IVIM parameters (P < 0.05), and there was no significant difference in D* value between the different pathological types (P > 0.05)., Conclusion: The D and f values showed correlation with different types of IOIP, and the sensitivity of the D value was higher than that of the f value. The D* value showed no significant distinction between pathological types of IOIP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pu, Liang, He, Shao, Zhou, Xiang, Li, Li and Ji.)

Hepaciviruses represent a group of viruses that pose a significant threat to the health of humans and animals. During the last decade, new members of the genus Hepacivirus have been identified in various host species worldwide, indicating the widespread distribution of genetically diversified hepaciviruses among animals. By applying unbiased high-throughput sequencing, a novel hepacivirus, provisionally designated Hepacivirus Q , was discovered in duck liver samples collected in Guangdong province of China. Genetic analysis revealed that the complete polyprotein of Hepacivirus Q shares 23.9-46.6% amino acid identity with other representatives of the genus Hepacivirus . Considering the species demarcation criteria for hepaciviruses, Hepacivirus Q should be regarded as a novel hepacivirus species of the genus Hepacivirus within the family Flaviviridae . Phylogenetic analyses also indicate the large genetic distance between Hepacivirus Q and other known hepaciviruses. Molecular detection of this novel hepacivirus showed an overall prevalence of 15.9% in duck populations in partial areas of Guangdong province. These results expand knowledge about the genetic diversity and evolution of hepaciviruses and indicate that genetically divergent hepaciviruses are circulating in duck populations in China.

Atherosclerosis (AS), with its intricate pathogenesis, is primarily responsible for the development and progression of cardiovascular diseases. Although drug development has made some achievements in AS therapy, limited targeting ability and rapid blood clearance remain great challenges for achieving superior clinical outcomes. Herein, ginsenoside (Re)- and catalase (CAT)-coloaded porous poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs) were prepared and then surface modified with U937 cell membranes (UCMs) to yield a dual targeted model and multimechanism treatment biomimetic nanosystem (Cat/Re@PLGA@UCM). The nanoparticles consisted of a core-shell spherical morphology with a favorable size of 112.7 ± 0.4 nm. Furthermore, UCM assisted the nanosystem in escaping macrophage phagocytosis and targeting atherosclerotic plaques. Meanwhile, loading with catalase might not only exhibit favorable antioxidant effects but also enable H 2 O 2 -responsive drug release ability. The Cat/Re@PLGA@UCM NPs also exhibited outstanding ROS scavenging properties, downregulating ICAM-1, TNF-α and IL-1β, while preventing angiogenesis to attenuate the progression of AS. Moreover, the nanodrugs displayed 2.7-fold greater efficiency in reducing the atherosclerotic area in ApoE -/- mouse models compared to free Re. Our nanoformulation also displayed excellent biosafety in response to long-term administration. Overall, our study demonstrated the superiority of UCM-coated stimuli-responsive nanodrugs for effective and safe AS therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The endothelium covers the internal lumen of the entire circulatory system and plays an important modulatory role in vascular homeostasis. Endothelium dysfunction, characterized by a vasoconstrictive, pro-inflammatory, and pro-coagulant state, usually manifests as a significant pathological process of vascular diseases, including hypertension, atherosclerosis (AS), stroke, diabetes mellitus, coronary artery disease, and cancer. Therefore, there is an urgent necessity to seek promising therapeutic drugs or remedies to ameliorate endothelial dysfunction-induced vascular ailments and complications. Recently, much attention has been attached to ginsenosides, the most significant active components of ginseng, which have always been referred to as "all-healing" and widely used for its extensively medicinal value. Surprisingly, ginsenosides have diverse biological activity which might be related to inflammation, apoptosis, oxidative stress, and angiogenesis. In this review, a brief introduction about endothelial dysfunction and ginsenosides was demonstrated, and the emphasis was put on summarizing multi-faceted pharmacological effects and underlying molecular mechanisms of ginsenosides on the endothelium, including vasorelaxation, anti-oxidation, anti-inflammation, and angio-modulation. Beyond that, nanotechnology to improve efficacy and the existing clinical trials of ginsenosides were concluded. Hopefully, our work will give suggestions for promoting clinical application of traditional Chinese medicine, e.g., hypertension, AS, diabetes, ischemic stroke, and cancer. This review provides a comprehensive base of knowledge for ginsenosides to prevention and treatment of vascular injury- related diseases with clinical significance.

Rapamycin (RAPA) functions as effectively clinical immunosuppressive agent, its significant tumor growth suppression effect via various pathways in diverse cancers, especially combined with photothermal therapy, is gaining a burgeoning attention. However, its critical defects, low solubility and poor stability, have severely hampered its further application. Herein, RAPA, indocyanine green (ICG) and epigallocatechin gallate (EGCG) serving as chemotherapeutic drug, photosensitizer and biomimetic coatings, respectively, were co-assembled into carrier-free, high biocompatible ICG-RAPA-EGCG nanoparticles (IRE NPs) for synergistic cancer therapy. Particularly, the bioinspired EGCG coatings not only improved the stability of IRE NPs under physiological conditions to avert NPs disassembly and drug release, but also maintained the photostability of ICG to achieve excellent photothermal response. The results indicated that the as-prepared IRE NPs displayed good monodispersity and enhanced stability at various stored media after introducing of EGCG. Compared with monotherapy of RAPA or ICG, IRE NPs showed higher dose-dependent toxicity in MCF-7 cells, HepG2 cells and HeLa cells, especially plus near-infrared laser irradiation. Furthermore, IRE NPs exhibited quicker uptake in cells, higher accumulation in tumor region (even in 48 h) than free ICG and effectively inhibited tumor growth without side effect in H22 tumor-bearing mice. Collectively, the carrier-free IRE NPs provided a simply alternative approach to fabricate RAPA/photosensitizer co-loaded nanoparticles for combinatorial tumor therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Outcrossing plant species are more likely to exhibit autonomous selfing in marginal habitats to ensure reproduction under conditions of limited pollinator and/or mate availability. Distyly is a classical paradigm that promotes outcrossing; however, little is known about the variation in floral traits associated with distylous syndrome in marginal populations. In this study, we compared the variation in floral traits including stigma and anther height, corolla tube length, herkogamy, and corolla diameter between the central and peripheral populations of the distylous Primula wannanensis , and assessed the variation of floral traits at early and late florescence stages for each population. To evaluate the potential consequences of the variation in floral traits on the mating system, we investigated seed set in each population under both open-pollinated and pollinator-excluded conditions. The flower size of both short- and long-styled morphs was significantly reduced in late-opening flowers compared with early opening flowers in both central and peripheral populations. Sex-organ reciprocity was perfect in early opening flowers; however, it was largely weakened in the late-opening flowers of peripheral populations compared with central populations. Of these flowers, disproportionate change in stigma height (elongated in S-morph and shortened in L-morph) was the main cause of reduced herkogamy, and seed set was fairly high under pollinator-excluded condition. Our results provide empirical support for the hypothesis on the evolution of delayed autonomous selfing in marginal populations of distylous species. Unsatisfactory pollinator service is likely to have promoted reproductive assurance of distylous plants with largely reduced herkogamy mimicking "homostyles.", Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Hu, He, Zhou and Shao.)

Hepaciviruses represent a group of viruses that pose a significant threat to the health of humans and animals. New members of the genus Hepacivirus in the family Flaviviridae have recently been identified in a wide variety of host species worldwide. Similar to the Hepatitis C virus (HCV), bovine hepacivirus (BovHepV) is hepatotropic and causes acute or persistent infections in cattle. BovHepVs are distributed worldwide and classified into two genotypes with seven subtypes in genotype 1. In this study, three BovHepV strains were identified in the samples of ticks sucking blood on cattle in the Guangdong province of China, through unbiased high-throughput sequencing. Genetic analysis revealed the polyprotein-coding gene of these viral sequences herein shared 67.7-84.8% nt identity and 76.1-95.6% aa identity with other BovHepVs identified worldwide. As per the demarcation criteria adopted for the genotyping and subtyping of HCV, these three BovHepV strains belonged to a novel subtype within the genotype 1. Additionally, purifying selection was the dominant evolutionary pressure acting on the genomes of BovHepV, and genetic recombination was not common among BovHepVs. These results expand the knowledge about the genetic diversity and evolution of BovHepV distributed globally, and also indicate genetically divergent BovHepV strains were co-circulating in cattle populations in China.

Diabetes is a metabolic disease caused by insufficient insulin secretion, action or resistance, in which insulin plays an irreplaceable role in the its treatment. However, traditional administration of insulin requires continuous subcutaneous injections, which is accompanied by inevitable pain, local tissue necrosis and hypoglycemia. Herein, a green and safe nanoformulation with unique permeability composed of insulin and ginsenosides is developed for transdermal delivery to reduce above-mentioned side effects. The ginsenosides are self-assembled to form shells to protect insulin from hydrolysis and improve the stability of nanoparticles. The nanoparticles can temporarily permeate into cells in 5 min and promptly excrete from the cell for deeper penetration. The insulin permeation is related to the disorder of stratum corneum lipids caused by ginsenosides. The skin acting as drug depot mantains the nanoparticles released continuously, therefore the body keeps euglycemic for 48 h. Encouraged by its long-lasting and effective transdermal therapy, ginsenosides-based nano-system is expected to deliver other less permeable drugs like proteins and peptides and benefit those who are with chronic diseases that need long-term medication., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Although considerable progress has recently been made in the taxonomic study of Asparagaceae, but the Polygonatum remains one of the most poorly investigated genus. Therefore, the present study was designed with the aim, to document the pollen micromorphology of closely related Polygonatum taxa and its taxonomic significance. Pollen micro-morphological features were observed using scanning electron microscopy-SEM). The pollen grains are monad, navicular, monocolpate, and radially symmetrical. A significant variation was observed in the exine sculpturing. Moreover, most of the Polygonatum taxa have perforate pollen while some of them were mixed with psilate to perforate, perforate to microreticulate, sometimes scabrate, gemmate with baculate. Hence, this study documented the pollen morphology of Polygonatum taxa and strengthens the taxonomic identification of the genus Polygonatum based on pollen characters, which helps and can be used as an additional tool for the correct identification and discrimination of the species of Polygonatum at generic and species level., (© 2021 Wiley Periodicals LLC.)

To better explore the pathophysiology of FA and its therapy, we aimed to establish a simple and practicable FA model with Freund's adjuvant and introduce an easy and reliable laboratory evaluation method for assessment of inflammation in intestinal segments at different anatomical locations. BALB/c mice were sensitized with ovalbumin combined with Freund's adjuvant. Complete Freund's adjuvant was chosen for the first sensitization and two weeks later incomplete Freund's adjuvant was used for a second sensitization. Two weeks later, the sensitized mice were challenged with 50 mg ovalbumin every other day. After the 6 challenge, all mice were assessed for systemic anaphylaxis, and then sacrificed for sample collection. All sensitized mice showed anaphylactic symptoms and markedly increased levels of serum ovalbumin-specific IgE and IgG1. The activity of mast cell protease-1 (mMCPT-1) was significantly increased in the serum and interstitial fluid of the duodenum, jejunum, ileum, and colon. A successful FA model was established, of which inflammation occurred in the duodenum, jejunum, ileum, and colon. This model provides a reliable and simple tool for analysis of the mechanism of FA and methods of immunotherapy. Moreover, combined detection of ovalbumin-specific antibody and local mMCPT-1 levels could potentially be used as the major indicator for assessment of food allergy., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

The intensive crosstalk between the liver and the intestine performs many essential functions. This crosstalk is important for natural immune surveillance, adaptive immune response regulation and nutrient metabolism and elimination of toxic bacterial metabolites. The interaction between the gut microbiome and bile acids is bidirectional. The gut microbiome regulates the synthesis of bile acids and their biological signaling activity and circulation via enzymes. Similarly, bile acids also shape the composition of the gut microbiome by modulating the host's natural antibacterial defense and the intestinal immune system. The interaction between bile acids and the gut microbiome has been implicated in the pathophysiology of many intestinal and extra intestinal diseases, especially liver diseases. As essential mediators of the gut-liver crosstalk, bile acids regulate specific host metabolic pathways and modulate the inflammatory responses through farnesoid X-activated receptor and G protein-coupled bile acid receptor 1. Several clinical trials have demonstrated the signaling effects of bile acids in the context of liver diseases. We hypothesize the existence of a gut microbiome-bile acids-liver triangle and explore the potential therapeutic strategies for liver diseases targeting the triangle., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interests regarding the publication of this paper., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Lycoris wulingensis S.Y. Zhang, a new species from Hunan Province (central South China), is described and illustrated. This new species is a fertile diploid plant and its karyotype is 2n = 22. It is most similar to L. × haywardii in morphology, but the latter is a hybrid species and distributed in East China and the plant is much larger. Amongst the original species, L. wulingensis is similar to L. radiata , but differs from it in its flowers being rose-red (vs. red) and stamens and tepals are nearly the same length (vs. stamens significantly longer than tepals)., (Si-Yu Zhang, Ying Huang, Pei Zhang, Ke-Run Zhu, Yong-Bing Chen, Jian-Wen Shao.)

Background: Type 2 diabetes mellitus (T2DM) has been strongly associated with an increased risk of developing cognitive dysfunction and dementia. The mechanisms of diabetes-associated cognitive dysfunction (DACD) have not been fully elucidated to date. Some studies proved lower cerebral blood flow (CBF) in the hippocampus was associated with poor executive function and memory in T2DM. Increasing evidence showed that diabetes leads to abnormal vascular endothelial growth factor (VEGF) expression and CBF changes in humans and animal models. In this study, we hypothesized that DACD was correlated with CBF alteration as measured by three-dimensional (3D) arterial spin labeling (3D-ASL) and VEGF expression in the hippocampus., Aim: To assess the correlation between CBF (measured by 3D-ASL and VEGF expression) and DACD in a rat model of T2DM., Methods: Forty Sprague-Dawley male rats were divided into control and T2DM groups. The T2DM group was established by feeding rats a high-fat diet and glucose to induce impaired glucose tolerance and then injecting them with streptozotocin to induce T2DM. Cognitive function was assessed using the Morris water maze experiment. The CBF changes were measured by 3D-ASL magnetic resonance imaging. VEGF expression was determined using immunofluorescence., Results: The escape latency time significantly reduced 15 wk after streptozotocin injection in the T2DM group. The total distance traveled was longer in the T2DM group; also, the platform was crossed fewer times. The percentage of distance in the target zone significantly decreased. CBF decreased in the bilateral hippocampus in the T2DM group. No difference was found between the right CBF value and the left CBF value in the T2DM group. The VEGF expression level in the hippocampus was lower in the T2DM group and correlated with the CBF value. The escape latency negatively correlated with the CBF value. The number of rats crossing the platform positively correlated with the CBF value., Conclusion: Low CBF in the hippocampus and decreased VEGF expression might be crucial in DACD. CBF measured by 3D-ASL might serve as a noninvasive imaging biomarker for cognitive impairment associated with T2DM., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Carrageenan (CRG) is a kind of linear sulfated polysaccharide that emerging as a promising substituent in food, pharmaceutics, and cosmetics. In recent years, biological properties of CRG polysaccharides such as antiviral, immunomodulatory, anticoagulant, antioxidant, and anticancer have been broadly studied, however, systematical summary of their structure-property relationships is scarce. Moreover, chemical modification is of great significance to explore biological and physiochemical properties of CRG polysaccharides which should be focused on. Chemical modification of CRG polysaccharides, e.g., carboxymethylation, thiolation, acetylation, phosphorylation, oversulfation, oxidization, and cationic or other derivatives, can improve their bioactivities and facilitate their applications in different biological systems. Hence, this review aims to elucidate structure-property relationships of CRG and its chemically modified derivatives with different structures and bioactivities, so as toxicity of CRG as food additive for the guidance of its clinical application., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Pet dogs are important companion animals that share the environment within households, and play an important role in local community life. In addition, pet dogs also are reservoirs of zoonotic agents, including Rickettsia spp., thus increasing the risk of rickettsial infections in humans. It's meaningful to investigate the epidemiology of rickettsial agents in pet dogs, and make contribute to the surveillance of rickettsioses in human in China., Results: In this study, a total of 496 pet dogs' blood samples and 343 ticks infested in pet dogs were collected, and the presence and prevalence of Rickettsia were determined by amplifying the partial gltA and 17-kDa genes, with an overall positive rate of 8.1 % in blood samples and 14.0 % in tick samples. In addition, the rrs, gltA, groEL, and ompA genes of rickettsial were also recovered to determine the species of Rickettsia detected furtherly. Sequencing blast and phylogenetic analyses revealed the presence of three human pathogenic Rickettsia species (Rickettsia raoultii, Candidatus Rickettsia tarasevichiae and Rickettsia felis) in samples associated with pet dogs. Moreover, all the sequences of Rickettsia that we obtained presented close relationship with others available in GenBank, and Rickettsia raoultii was the most predominant Rickettsia species infected in pet dogs' blood samples or in tick samples., Conclusions: This study provides the molecular epidemiology data about the Rickettsia spp. infection associated with pet dogs in urban areas of Harbin city. Three rickettisae species pathogenic to humans were identified from pet dogs' blood and the infested ticks in urban areas of Harbin city. Considering the intimate relationship between human and pets, these results indicate the potential transmission risk of human rickettisal infections from pet dogs through ectoparasites, and also highlighting that more attention should be paid to rickettsial infection in pet dogs and the infested ticks from the "One health" perspective.