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Abstract. The rarity of Francisella novicida infection in humans is well-known, and the F. novicida cases occur in immunocompromised patients or those with underlying health problems. Herein, we report the case of a patient with long-term diabetes who died following F. novicida infection that caused multiple organ failure, although F. novicida was effectively eliminated using antimicrobial therapy. Microbiological confirmation of F. novicida infection relies on metagenomic next-generation sequencing (mNGS) and pdpD-2 gene-specific identification. This study highlights the importance of early pathogen diagnosis in severely infected patients, particularly in cases of F. novicida, and indicates that mNGS is a useful tool for early diagnosis.

The increase in emerging and reemerging infectious diseases has underscored the need for the prompt monitoring of intact infectious viruses and the quick assessment of their infectivity. However, molecular techniques cannot distinguish between intact infectious and noninfectious viruses. Here, two distinct methodologies have been developed for the expeditious and dependable quantification of intact infectious H1N1 virus, and several experiments have been conducted to substantiate their efficacy. One is an integrated cell absorption quantitative polymerase chain reaction (qPCR) method (ICA-qPCR), and the other is a combined propidium monoazide qPCR method (PMA-qPCR). The quantification limit is 100 cell culture infective dose 50 % (CCID50)/mL in ICA-qPCR following a 1.5-hour cell absorption or 126 CCID50/mL after a 15-minute incubation. For PMA-qPCR, the limit was 2,512 CCID50/mL. The number of genome copies quantified by the ICA-qPCR and PMA-qPCR methods was strongly correlated with the infectious titer determined by the CCID50 assay, thereby enabling the estimation of virus infectivity. The ICA-qPCR and PMA-qPCR methods are both suitable for the identification and quantification of intact infectious H1N1 virus in inactivated samples, wastewater, and biological materials. In conclusion, the ICA-qPCR and PMA-qPCR methods have distinct advantages and disadvantages, and can be used to quantify intact infectious viruses rapidly. These methodologies can facilitate the identification of the presence of intact infectious viruses in wastewater or on pathogen-related physical surfaces in high-level biosafety laboratories and medical facilities. Furthermore, these methodologies can also be utilized to detect other highly pathogenic pathogens.

Ebola virus (EBOV) belongs to Filoviridae family possessing single-stranded negative-sense RNA genome, which is a serious threat to human health. Nowadays, no therapeutics have been proven to be successful in efficiently decreasing the mortality rate. RNA binding proteins (RBPs) are reported to participate in maintaining cell integrity and regulation of viral replication. However, little is known about whether and how RBPs participate in regulating the life cycle of EBOV. In our study, we found that RNA binding motif protein 4 (RBM4) inhibited the replication of EBOV in HEK293T and Huh-7 cells by suppressing viral mRNA production. Such inhibition resulted from the direct interaction between the RRM1 domain of RBM4 and the “CU” enrichment elements located in the PE1 and TSS of the 3′-leader region within the viral genome. Simultaneously, RBM4 could upregulate the expression of some cytokines involved in the host innate immune responses to synergistically exert its antiviral function. The findings therefore suggest that RBM4 might serve as a novel target of anti-EBOV strategy.

Nipah virus (NiV), a highly pathogenic Henipavirus in humans, has been responsible for annual outbreaks in recent years. Experiments involving live NiV are highly restricted to biosafety level 4 (BSL-4) laboratories, which impedes NiV research. In this study, we developed transcription and replication-competent NiV-like particles (trVLP-NiV) lacking N, P, and L genes. This trVLP-NiV exhibited the ability to infect and continuously passage in cells ectopically expressing N, P, and L proteins while maintaining stable genetic characteristics. Moreover, the trVLP-NiV displayed a favourable safety profile in hamsters. Using the system, we found the NiV nucleoprotein residues interacting with viral RNA backbone affected viral replication in opposite patterns. This engineered system was sensitive to well-established antiviral drugs, innate host antiviral factors, and neutralizing antibodies. We then established a high-throughput screening platform utilizing the trVLP-NiV, leading to the identification of tunicamycin as a potential anti-NiV compound. Evidence showed that tunicamycin inhibited NiV replication by decreasing the infectivity of progeny virions. In conclusion, this trVLP-NiV system provided a convenient and versatile molecular tool for investigating NiV molecular biology and conducting antiviral drug screening under BSL-2 conditions. Its application will contribute to the development of medical countermeasures against NiV infections.

Background: Acute myeloid leukemia (AML) is an aggressive cancer with variable treatment responses. While clinical factors such as age and genetic mutations contribute to prognosis, recent studies suggest that CT attenuation scores may also predict treatment outcomes. This study aims to develop a nomogram combining clinical and CT-based factors to predict treatment response and guide personalized therapy for AML patients. Methods: This retrospective study included 74 newly diagnosed AML patients who underwent unenhanced abdominal CT scans within one week before receiving their first induction chemotherapy. Clinical biomarkers of tumor burden were also collected. Patients were classified into two groups based on treatment response: complete remission (CR; n = 24) and non-complete remission (NCR; n = 50). Multivariable logistic regression was used to identify independent predictors of treatment response. Predictive performance was evaluated using receiver operating characteristic (ROC) curves, and model consistency was assessed through calibration and decision curve analysis (DCA). Results: Significant differences in hemoglobin (Hb), platelets (Plt), and CT attenuation scores were observed between the CR and NCR groups (all p < 0.05). Multivariable logistic regression identified Hb, Plt, and CT attenuation scores as independent predictors of treatment response. A nomogram incorporating these factors demonstrated excellent predictive performance, with an area under the curve (AUC) of 0.912 (95% CI: 0.842–0.983), accuracy of 0.865 (95% CI: 0.765–0.933), sensitivity of 0.880 (95% CI: 0.790–0.970), and specificity of 0.833 (95% CI: 0.684–0.982). The CR nomogram displayed significant clinical value and excellent goodness of fit. Conclusions: The nomogram, which incorporates Hb, Plt, and CT attenuation scores, provides valuable insights into predicting treatment response in AML patients. This model offers strong discriminatory ability and could enhance personalized treatment planning and prognosis prediction for AML.

ABSTRACT Monkeypox virus (MPXV) poses a global health threat. Droplet digital PCR (ddPCR) holds potential as an accurate diagnostic tool for clinical microbiology. However, there is limited literature on the applicability of ddPCR in clinical settings. In this study, the clinical features of patients with MPXV during the initial outbreak in China in June 2023 were reviewed, and an optimized ddPCR method with dilution and/or inhibitor removal was developed to enhance MPXV detection efficiency. Eighty-two MPXV samples were tested from nine different clinical specimen types, including feces, urine, pharyngeal swabs, anal swabs, saliva, herpes fluid, crust, and semen, and the viral load of each specimen was quantified. A comparative analysis was performed with qPCR to assess sensitivity and specificity and to investigate the characteristics of MPXV infection by analyzing viral loads in different clinical specimens. Consequently, common pharyngeal and gastrointestinal symptoms were observed in patients with MPXV. The optimized ddPCR method demonstrated relatively high sensitivity for MPXV quantification in the clinical materials, with a limit of detection of 0.1 copies/μL. This was particularly evident in low-concentration samples like whole blood, semen, and urine. The optimized ddPCR demonstrated greater detection accuracy compared with normal ddPCR and qPCR, with an area under the curve (AUC) of 0.939. Except for crust samples, viral loads in the specimens gradually decreased as the disease progressed. Virus levels in feces and anal swabs kept a high detection rate at each stage of post-symptom onset, and feces and anal swabs samples may be suitable for clinical diagnosis and continuous monitoring of MPXV.IMPORTANCEThe ddPCR technique proved to be a sensitive and valuable tool for accurately quantifying MPXV viral loads in various clinical specimen types. The findings provided valuable insights into the necessary pre-treatment protocols for MPXV diagnosis in ddPCR detection and the potentially suitable sample types for collection. Therefore, such results can aid in comprehending the potential characteristics of MPXV infection and the usage of ddPCR in clinical settings.

Wang Yangming’s emphasis on the concept of oneness establishes a significant connection between his philosophy and mysticism. This comparative study draws upon his mystical encounters and conceptual framework. Although “all things form one body” appears to be a typical formula of extrovertive mysticism, his doctrine is more inclined to be classified as a type of introvertive mysticism because of the special definition of “thing” and the deep involvement of heart–mind. The realm of oneness is based on the mode of a heart–mind pervading the entirety of the universe and all things, with the core concept of liangzhi as both pure consciousness and the base of the world. The adoption of a mystical philosophical perspective highlights Wang’s theory of oneness as a spiritual philosophy, transcending general ethical claims, thus enriching our understanding of Wang’s philosophy of mind.

Abstract. Parvovirus B19 (B19V) infection can cause pure red cell aplasia (PRCA) in patients with human immunodeficiency virus (HIV) infection. Intravenous immunoglobulin (IVIG) is a preferred treatment option. From July 2019 to March 2022, four patients with HIV infection were admitted to Guangzhou Eighth People’s Hospital with dizziness and fatigue and were diagnosed with PRCA. Blood investigations revealed severe anemia and the B19V genome. Therefore, the four patients were diagnosed with B19V-induced PRCA. All four patients received red blood cell transfusion in the setting of antiretroviral therapy, and two of the four patients received intravenous immunoglobulin (IVIG). After 3–7 months of treatment, all four patients recovered, although two did not receive IVIG. This suggests that IVIG is not always necessary for the treatment of PRCA in patients with HIV infection and that effective antiretroviral therapy and immunological reconstitution play an important role in the eradication of parvovirus.

Our patient, a 48-year-old man from Guangdong’s coastal region, worked selling and processing oysters and other seafood. He started experiencing swelling and pain in his left knee on October 4, 2022, and they got worse over time. The findings of mNGS test showed Vibrio vulnificus infection. The patient had AIDS, hepatitis A and hepatitis B concurrently. He was admitted to the hospital’s intensive care unit (ICU) for treatment as his symptoms worsened. We refrained from performing an amputation because the family members expressed a desire to keep the limb. The limb was managed with regular dressing changes, thorough debridement, wound closure, ongoing VSD drainage, and local antibiotic irrigation. The patient’s organ function eventually returned to normal, and the systemic infection got better. On November 1, the wound’s new granulation tissue had grown well and had gradually crept to cover 80% of the wound. The tissue’s blood flow had also improved, indicating a trend of growth and healing.

ABSTRACTMagnitude and diversity of gut microbiota and metabolic systems are critical in shaping human health and diseases, but it remains largely unclear how complex metabolites may selectively regulate gut microbiota and determine health and diseases. Here, we show that failures or compromised effects of anti-TNF-α therapy in inflammatory bowel diseases (IBD) patients were correlated with intestinal dysbacteriosis with more pro-inflammatory bacteria, extensive unresolved inflammation, failed mucosal repairment, and aberrant lipid metabolism, particularly lower levels of palmitoleic acid (POA). Dietary POA repaired gut mucosal barriers, reduced inflammatory cell infiltrations and expressions of TNF-α and IL-6, and improved efficacy of anti-TNF-α therapy in both acute and chronic IBD mouse models. Ex vivo treatment with POA in cultured inflamed colon tissues derived from Crohn’s disease (CD) patients reduced pro-inflammatory signaling/cytokines and conferred appreciable tissue repairment. Mechanistically, POA significantly upregulated the transcriptional signatures of cell division and biosynthetic process of Akkermansia muciniphila, selectively increased the growth and abundance of Akkermansia muciniphila in gut microbiota, and further reprogrammed the composition and structures of gut microbiota. Oral transfer of such POA-reprogrammed, but not control, gut microbiota induced better protection against colitis in anti-TNF-α mAb-treated recipient mice, and co-administration of POA with Akkermansia muciniphila showed significant synergistic protections against colitis in mice. Collectively, this work not only reveals the critical importance of POA as a polyfunctional molecular force to shape the magnitude and diversity of gut microbiota and therefore promote the intestinal homeostasis, but also implicates a new potential therapeutic strategy against intestinal or abenteric inflammatory diseases.

Background Parathyroidectomy (PTX) is a treatment for hyperparathyroidism (HPT) and has uncertain risks and benefits. The aim of this study was to evaluate the effect of PTX versus nonoperative treatment among nondiabetic hemodialysis patients.Methods A retrospective matched cohort study was performed. Each PTX patient was matched with one patient who had severe HPT but rejected PTX. The patients were matched by sex, birth date, date of first dialysis, nondiabetic status, and left ventricular ejection fraction. The serum markers, survival, main adverse cardiovascular and cerebrovascular event (MACCE) rates, and hospitalization were compared between the PTX patients and matched non-PTX patients.Results There were 1143 patients at our center in the Chinese National Renal Data System (CNRDS) between 2010 and 2020. Of these, 75 PTX patients were matched with 75 non-PTX patients. Rapid decreases in the mean intact parathyroid hormone, calcium and phosphorus concentrations, and a gradual increase in hemoglobin concentration were observed in the PTX group. The mortality was 2.9 per 100 patient-years in the PTX group and 10.9 per 100 patient-years in the non-PTX group (p

Monkeypox is a zoonotic disease caused by the monkeypox virus (MPXV), which is a potential biological warfare agent of bioterrorism and poses the greatest threat to the world’s public biosafety and health after variola virus (VARV). While the coronavirus disease 2019 (COVID-19) pandemic has not ended yet, monkeypox is spreading menacingly. The first case of monkeypox in a nonendemic country was confirmed on May 6th, 2022, while the first imported case from Asia was found on June 21st. There were more than 16 thousand reported cases as of July 23rd, the day the World Health Organization (WHO) declared the global monkeypox outbreak a public health emergency of international concern (PHEIC) at the same level as smallpox and COVID-19; while there were more than 53 thousand cases as of September 1st. Therefore, we will propose relevant biosafety prevention and control strategies after analyzing the etiology of the 2022 multi-country monkeypox outbreak from the biological feature, transmissibility, epidemic, and variability of MPXV.

Influenza A viruses continue to be a serious health risk to people and result in a large-scale socio-economic loss. Avian influenza viruses typically do not replicate efficiently in mammals, but through the accumulation of mutations or genetic reassortment, they can overcome interspecies barriers, adapt to new hosts, and spread among them. Zoonotic influenza A viruses sporadically infect humans and exhibit limited human-to-human transmission. However, further adaptation of these viruses to humans may result in airborne transmissible viruses with pandemic potential. Therefore, we are beginning to understand genetic changes and mechanisms that may influence interspecific adaptation, cross-species transmission, and the pandemic potential of influenza A viruses. We also discuss the genetic and phenotypic traits associated with the airborne transmission of influenza A viruses in order to provide theoretical guidance for the surveillance of new strains with pandemic potential and the prevention of pandemics.

In order to obtain the best extraction process of smoked Amomum tsaoko(SDAT) oleoresin, the extraction solvent, extraction temperature, solid-liquid ratio, extraction time and particle size were regarded as the influence factors. On the basis of single factor experiment, the eexperimental design of three factors and three levels was used by Box-Benhnken central composite method, according to the extraction rate of SDAT oleoresin as the response value, and the extraction conditions were further optimized by response surface methodology(RSM). The results showed that the optimum process conditions of SDAT oleoresin was as follows: Anhydrous methanol as solvent, extraction temperature was 75 ℃, solid-liquidratio was 1:20(g/mL), extraction time was 7 h and particle size was 80 mesh. The regression equation predicted that the theoretical extraction rate of SDAT could reach 9.57%, the average extraction rate of the three validation experiments was 9.48%, and the predicted value was close to the actual result. And 58 compounds were identified by GC-TOF-MS, including alcohols(31.59%), aldehydes(21.13%), alkenes(1.23%), ketones(1.56%), esters(2.38%) and phenols(0.79%), 1,8-eucalyptol(9.28%), α-terpineol(3.55%), gera-niol(8.4%), trans citral(5.78%), 2-methyl-3-ph-enylpropanal(6.33%), etc. Through the determination of the best process of SDAT oleoresin, the detected components are mainly concentrated in alcohols and aldehydes, which provides a theoretical basis for the nutritional components and biological activity of grass fruit oleoresin in the later stage.

The gut-lung axis has been implicated as a potential therapeutic target in lung disorders. While increasing evidence suggests that gut microbiota plays a critical role in regulating host immunity and contributing to tuberculosis (TB) development and progression, the underlying mechanisms whereby gut microbiota may impact TB outcomes are not fully understood. Here, we found that broad-spectrum antibiotics treatment increased susceptibility to Mycobacterium tuberculosis (M. tuberculosis) infection and modulated pulmonary inflammatory responses in mouse M. tuberculosis infection model. We then identified a commensal gut bacteria-regulated lncRNA, termed lncRNA-CGB, which was down-regulated by dysbiosis of gut microbiota during TB infection. Furthermore, we found that Bacteroides fragilis (B. fragilis) was a direct regulator of lncRNA-CGB, and oral administration of B. fragilis enhanced expression of lncRNA-CGB and promoted anti-TB immunity. Genomic knock-out of lncRNA-CGB led to reduced IFN-γ expression and impaired anti-TB immunity, therefore leading to detrimental effects on M. tuberculosis infection. Mechanistically, lncRNA-CGB interacted with EZH2 and negatively regulated H3K27 tri-methylation (H3K27Me3) epigenetic programming, leading to enhanced IFN-γ expression. Thus, this work not only uncovered previously unrecognized importance of gut bacteria-lncRNA-EZH2-H3K27Me3 axis in conferring immune protection against TB but also identified a potential new paradigm to develop a microbiota-based treatment against TB and potentially other diseases.

This paper is concerned with the problem of asymptotic stability for a class of stochastic differential equations with impulsive effects. A sufficient criterion on asymptotic stability is derived for such impulsive stochastic differential equations via Lyapunov stability theory, bounded difference condition and martingale convergence theorem. The results show that the impulses can facilitate the stability of the stochastic differential equations when the original system is not stable. Finally, the feasibility of our results is confirmed by two numerical examples and their simulations.

Cervical cancer is one of the most fatal malignancies in females. Acquired resistance to chemotherapeutic agent is one reason behind this lethality. In this study, we developed cisplatin resistance cell line, subsequently examined the molecular mechanisms linked. Transcriptome sequencing technology was utilized to compare the various expression models between the cisplatin-resistant cell line (Hela/DDP) and its parental cell line human cervical adenocarcinoma Hela. The present study has identified 2,312 differentially expressed genes (DEGs). Results showed there were 1,437 up-regulated genes and 875 down-regulated ones. Databases analysis including Gene ontology (GO), Cluster of Orthologous Groups of proteins (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to reveal potential molecular mechanisms. We studied AKT3, a crucial gene in the PI3K/AKT pathway which clustered the most DEGs. Silencing AKT3 in Hela/DDP could enhance its sensibility to cisplatin. Quantitative real-time reverse transcription PCR (qRT-PCR) and western blot experiments were showed that expression of AKT3 was decreased after siRNA interference and inhibitor treatment. CCK-8 experiments showed that low expression of Akt3/pAkt enhanced the sensitivity of drug-resistant cells to cisplatin. Apoptotic analysis demonstrated that inhibition of AKT3 increased the rate of Hela/DDP apoptosis. Our results suggest a novel mechanism by which upregulated expression of AKT3 in cervical cancer may lead to resistance to cisplatin.

The national surveys on giant panda (Ailuropoda melanoleuca) population and habitat quality have shown a high-density population of this species in the Qinling Mountains, China. We investigated five adjacent nature reserves (NR), i.e., the key distribution area of giant pandas in the Qinling Mountains, to model and identify the potential dispersal routes for giant pandas. We hypothesized that giant pandas will spread to neighboring areas when the population of the species keeps increasing. Habitat suitability was firstly evaluated based on environmental and disturbance factors. We then identified source and sink patches for giant pandas’ dispersal. Further, Minimum Cumulative Resistance (MCR) model was applied to calculate cost of movement. Finally, the Current Theory was adopted to model linkages between source and sink patches to explore potential dispersal routes of giant pandas. Our results showed that (1) the three large source patches and eight potential sink patches were identified; (2) the 14 potential corridors were predicted for giant pandas dispersing from source patches to the neighboring areas; (3) through the predicted corridors, the giant pandas in the source patches could disperse to the west, the south and the east sink patches. Our research revealed possible directional patterns for giant pandas’ dispersal in their key distribution area of the Qinling Mountains, and can provide the strong recommendations in policy and conservation strategies for improving giant panda habitat management in those identified sink patches and also potential dispersal corridors.

There is a high incidence of radiation enteritis (RE) after abdominal radiotherapy. The occurrence of RE seriously affects the treatment and quality of life of patients; however, its pathogenesis is complex and there are no effective drugs for its prevention or treatment. Intestinal ischemia plays an important role in the occurrence of enteritis. Previous studies have shown that targeting GTP-cyclohydrolase 1 (Gch1) to improve intestinal ischemia could be a new strategy to prevent and treat RE. A high content of the naturally occurring phthalide derivative ligustilide (LIG) has been found in the plant drug Rhizoma Ligustici Chuanxiong for the treatment of cardiovascular diseases. The purpose of this study was to evaluate the protective effects of LIG on RE. Ionizing radiation (IR) rat and endothelial cell models were used to observe and record rat body weights and stool morphologies, measure intestinal blood perfusion by laser Doppler blood flow imaging, determine the diastolic functions of mesenteric arteries, detect the levels of Gch1/BH4/eNOS pathway-related proteins and regulatory molecules in the mesenteric arteries and endothelial cells, and predict affinity by molecular docking technology. The results showed that LIG significantly improved the body weights, loose stools, intestinal villi lengths, intestinal perfusion and vasodilatory functions of IR rats. LIG also significantly improved Gch1 protein and BH4 levels in the mesenteric arteries and endothelial cells after IR, increased the NO content, reduced superoxide accumulation, and improved p-eNOS (Ser1177) levels in endothelial cells. LIG has good affinity for Gch1, which significantly improves its activity. These results indicate that LIG is the preferred compound for the prevention and treatment of RE by improving intestinal ischemia through the Gch1/BH4/eNOS pathway. This study provides a theoretical basis and new research ideas for the development of new drugs for RE.

The existence of solutions is used the premise of discussing other properties of dynamic systems. The goal of this paper is to investigate the fundamental properties of nonlinear stochastic differential equations via the Khasminskii test, including the local existence and global existence of the solutions. Firstly, a fundamental result is given as a lemma to verify the local existence of solutions to the considered equation. Then, the equivalent proposition for the global existence and the fundamental principle for the Khasminskii test are formally established. Moreover, the classical Khasminskii test is generalized to the cases with high-order estimates and heavy nonlinearity for the stochastic derivatives of the Lyapunov functions. The role of the noise in this aspect is especially investigated, some concrete criteria are obtained, and an application for the role of the noise in the persistence of financial systems is accordingly provided. As another application of the fundamental principle, a new version of the Khasminskii test is established for the delayed stochastic systems. Finally the conclusions obtained in the paper are verified by simulation. The results show that, under weaker conditions, the global existence of better solutions to stochastic systems to those in the existing literature can be obtained.

Black hairy tongue (BHT) is characterized by a discolored, hairy tongue. We herein report two cases of BHT associated with antibacterial agents and review previous cases. In Case 1, a 17-year-old girl with a central neurocytoma was administered intravenous piperacillin–tazobactam for postoperative infection, and BHT developed 12 days later. Her symptoms resolved 8 days after she discontinued the piperacillin–tazobactam and brushed her tongue three times daily. In Case 2, a 65-year-old man was administered intravenous piperacillin–tazobactam and levofloxacin to treat multidrug-resistant Pseudomonas aeruginosa , and BHT developed 15 days later. The piperacillin–tazobactam was discontinued and the patient brushed his tongue, and the discoloration gradually subsided thereafter. However, the BHT reappeared after linezolid treatment. The patient had adverse drug reactions to both the piperacillin–tazobactam and linezolid treatments. The BHT might have been related to antibiotic use in both cases. We identified 19 cases of antibiotic-related BHT in a literature search, but none were related to piperacillin–tazobactam use. In all cases, symptoms resolved after discontinuation of the drug and brushing of the tongue. BHT may be a rare adverse effect of antibiotics. Treatment strategies include removal of the causative agents, mechanical debridement, and good oral hygiene.

Objective We systematically investigated the cytotoxic effects of ricin in primary pulmonary alveolar macrophages (PAMs). Methods Primary PAMs were isolated from BALB/c mice. The cytotoxic effects of ricin were investigated in vitro by optical and transmission electron microscopy, detection of the inflammatory cytokine response, proteomic analysis, and subsequent biological functional analysis. Results Ricin induced shrinkage, apoptosis, vacuolization, and multi-organelle lesions in primary PAMs as demonstrated by optical and transmission electron microscopy. Ricin also induced a pronounced pro-inflammatory cytokine response in primary PAMs, including induction of tumor necrosis factor-α, interferon-γ, interleukin (IL)-1, IL-2, IL-6, IL-12, C-C motif chemokine ligand 2, and C-X-C motif chemokine ligand 2, while the anti-inflammatory cytokines IL-4 and IL-10 were less affected. Proteomic analysis and subsequent biological functional analysis identified eight proteins that were up/downregulated by ricin treatment and which might thus contribute to ricin toxicity. These proteins were involved in various functions, including redox, molecular chaperone, glycolysis, protein translation, and protein degradation functions. Conclusion The results of the present study further our understanding of the pathogenic mechanism of inhalational ricin poisoning.

Objective This study was performed to develop a murine aerosol infection model of brucellosis to investigate the pathogenicity and immune reactions induced by aerosolized Brucella and to identify key proteins associated with Brucella infection in lung tissue. Methods BALB/c mice were exposed to aerosolized Brucella melitensis 5 (M5) for 30 minutes and killed at 1, 3, 7, and 15 days post-exposure. Clinical observation, pathological analysis of lung tissue, and cytokine expression detection were then performed. Proteomic analysis based on two-dimensional electrophoresis and mass spectrometry was used to identify proteins exhibiting significant changes in expression in lung tissues during Brucella infection. Results Pathological analysis revealed alveolar wall thickening, telangiectasia with hyperemia, inflammatory cell infiltration, large areas of congestion and bleeding, and areas of focal necrosis. The T-helper 1 type immune response played an important role during aerosol infection, and 12 differentially expressed proteins were involved in the infectious process in lung tissue. Conclusion These results contribute to our understanding of the pathogenic process of Brucella in the lung tissue of BALB/c mice challenged with aerosolized Brucella . Some of the identified proteins may be potential targets in future therapeutic strategies.

Objective To develop a bioluminescence-labelled bacterial infection model to monitor the colonization and clearance process of Escherichia coli O157:H7 in the lungs of mice following influenza A virus/Puerto Rico/8/34 (H1N1) strain (IAV/PR8) infection. Methods BALB/c mice were administered IAV/PR8 or 0.01 M phosphate-buffered saline (PBS; pH 7.4) intranasally 4 days prior to intranasal administration of 1 × 10 7 colony-forming units (CFU) of E. coli O157:H7-lux. Whole-body bioluminescent signals were monitored at 10 min, 4 h, 8 h, 12 h, 16 h and 24 h post-bacterial infection. Lung bioluminescent signals and bacterial load (CFU/g) were monitored at 4 h, 8 h, 12 h, 16 h and 24 h post-bacterial infection. Results Prior IAV/PR8 infection of mice resulted in a higher level of bacterial colonization and a lower rate of bacterial clearance from the lungs compared with mice treated with PBS. There were also consistent findings between the bioluminescence imaging and the CFU measurements in terms of identifying bacterial colonization and monitoring the clearance dynamics of E. coli O157:H7-lux in mouse lungs. Conclusion This novel bioluminescence-labelled bacterial infection model rapidly detected bacterial colonization of the lungs and monitored the clearance dynamics of E. coli O157:H7-lux following IAV/PR8 infection.

At least 15 cases of human beings infected with H5N6 have been reported since 2014, of which at least nine were fatal. The highly pathogenic avian H5N6 influenza virus may pose a serious threat to both public health and the poultry industry. However, the molecular features promoting the adaptation of avian H5N6 influenza viruses to mammalian hosts is not well understood. Here, we sequentially passaged an avian H5N6 influenza A virus (A/Northern Shoveler/Ningxia/488-53/2015) 10 times in mice to identify the adaptive amino acid substitutions that confer enhanced virulence to H5N6 in mammals. The 1st and 10th passages of the mouse-adapted H5N6 viruses were named P1 and P10, respectively. P1 and P10 displayed higher pathogenicity in mice than their parent strain. P10 showed significantly higher replication capability in vivo and could be detected in the brains of mice, whereas P1 displayed higher replication efficiency in their lungs but was not detectable in the brain. Similar to its parent strain, P10 remained no transmissible between guinea pigs. Using genome sequencing and alignment, multiple amino acid substitutions, including PB2 E627K, PB2 T23I, PA T97I, and HA R239H, were found in the adaptation of H5N6 to mice. In summary, we identified amino acid changes that are associated with H5N6 adaptation to mice.

Ebola virus emerged in West Africa in December 2013. The high population mobility and poor public health infrastructure in this region led to the development of the largest Ebola virus disease (EVD) outbreak to date.On September 26, 2014, China dispatched a Mobile Biosafety Level-3 Laboratory (MBSL-3 Lab) and a well-trained diagnostic team to Sierra Leone to assist in EVD diagnosis using quantitative real-time PCR, which allowed the diagnosis of suspected EVD cases in less than 4 hours from the time of sample receiving. This laboratory was composed of three container vehicles equipped with advanced ventilation system, communication system, electricity and gas supply system. We strictly applied multiple safety precautions to reduce exposure risks. Personnel, materials, water and air flow management were the key elements of the biosafety measures in the MBSL-3 Lab. Air samples were regularly collected from the MBSL-3 Lab, but no evidence of Ebola virus infectious aerosols was detected. Potentially contaminated objects were also tested by collecting swabs. On one occasion, a pipette tested positive for EVD. A total of 1,635 suspected EVD cases (824 positive [50.4%]) were tested from September 28 to November 11, 2014, and no member of the diagnostic team was infected with Ebola virus or other pathogens, including Lassa fever. The specimens tested included blood (69.2%) and oral swabs (30.8%) with positivity rates of 54.2% and 41.9%, respectively. The China mobile laboratory was thus instrumental in the EVD outbreak response by providing timely and reliable diagnostics.The MBSL-3 Lab significantly contributed to establishing a suitable laboratory response capacity during the emergence of EVD in Sierra Leone.

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