Anesthesia/surgery-induced learning and memory dysfunction by inhibiting mitophagy-mediated NLRP3 inflammasome inactivation in aged mice.

Postoperative cognitive dysfunction (POCD) is a common postoperative complication, not only affects the quality of life of the elderly and increases the mortality rate, but also brings a greater burden to the family and society. Previous studies demonstrated that Nod-like receptor protein 3 (NLRP3) inflammasome participates in various inflammatory and neurodegenerative diseases. However, possible mitophagy mechanism in anesthesia/surgery-elicited NLRP3 inflammasome activation remains to be elucidated. Hence, this study clarified whether mitophagy dysfunction is related to anesthesia/surgery-elicited NLRP3 inflammasome activation. POCD model was established in aged C57BL/6 J mice by tibial fracture fixation under isoflurane anesthesia. Morris Water Maze (MWM) was used to evaluate learning and memory abilities. We found that in vitro experiments, lipopolysaccharide (LPS) significantly facilitated NLRP3 inflammasome activation and mitophagy inhibition in BV2 cells. Rapamycin restored mitophagy and improved mitochondrial function, and inhibited NLRP3 inflammasome activation induced by LPS. In vivo experiments, anesthesia and surgery caused upregulation of hippocampal NLRP3, caspase recruitment domain (ASC) and interleukin-1ß (IL-1 ß), and downregulation of microtubule-associated protein light chain 3II (LC3II) and Beclin1 in aged mice. Olaparib inhibited anesthesia/surgery-induced NLRP3, ASC, and IL-1ß over-expression in the hippocampus, while upregulated the expression of LC3II and Beclin1. Furthermore, Olaparib improved cognitive impairment in older mice. These results revealed that mitophagy was involved in NLRP3 inflammasome-mediated anesthesia/surgery-induced cognitive deficits in aged mice. Overall, our results suggested that mitophagy was related in NLRP3 inflammasome-induced cognitive deficits after anesthesia and surgery in aged mice. Activating mitophagy may have clinical benefits in the prevention of cognitive impairment induced by anesthesia and surgery in elderly patients.

Epidemiological characteristics of human rabies cases reported by sites in China from 2006 to 2022.

BACKGROUND: Rabies is an incessant public health threat in China. The Ministry of Health implemented the Central Payment for Rabies Prevention and Control Project to assist with rabies prevention and control in a few representative provinces in 2006. METHODS: Data on human rabies cases reported by the National Infectious Disease Reporting Information Management System and national surveillance sites from 2006 to 2022 were collected, and statistical and multivariate analyses were then used to assess the effectiveness of current prevention and control efforts. RESULTS: During 2006-2022, a total of 2025 human rabies cases were collected by the national surveillance sites, with incidence rates far above the national average, but the incidence rate was consistent with the national trend. Human rabies cases demonstrated a dual peak distribution in terms of exposure and onset dates, with the peak exposure dates falling mostly in the spring and summer and the peak onset dates occurring mostly in the summer and autumn. Three danger categories are shown by the geographical distribution: high, medium and low. Dogs had a high infection rate (86.93%), with own domesticated dogs accounting for the majority of infections. The rates of post-exposure prophylaxis are not constant. The median incubation period was 71 days. CONCLUSIONS: Various measures and policies implemented by the government have played a key role in reducing the incidence of rabies. To effectively prevent and control the resurgence of epidemics and halt the spread of the virus among host animals, it is imperative to prioritize and implement a robust dog management system, accelerate research and development of animal vaccines and improve the level of post-exposure prophylaxis.

Rabies Virus Regulates Inflammatory Response in BV-2 Cells through Activation of Myd88 and NF-κB Signaling Pathways via TLR7.

Rabies is a fatal neurological infectious disease caused by rabies virus (RABV), which invades the central nervous system (CNS). RABV with varying virulence regulates chemokine expression, and the mechanisms of signaling pathway activation remains to be elucidated. The relationship between Toll-like receptors (TLRs) and immune response induced by RABV has not been fully clarified. Here, we investigated the role of TLR7 in the immune response induced by RABV, and one-way analysis of variance (ANOVA) was employed to evaluate the data. We found that different RABV strains (SC16, HN10, CVS-11) significantly increased CCL2, CXCL10 and IL-6 production. Blocking assays indicated that the TLR7 inhibitor reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). The activation of the Myd88 pathway in BV-2 cells stimulated by RABV was TLR7-dependent, whereas the inhibition of Myd88 activity reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). Meanwhile, the RABV stimulation of BV-2 cells resulted in TRL7-mediated activation of NF-κB and induced the nuclear translocation of NF-κB p65. CCL2, CXCL10 and IL-6 release was attenuated by the specific NF-κB inhibitor used (p < 0.01). The findings above demonstrate that RABV-induced expression of CCL2, CXCL10 and IL-6 involves Myd88 and NF-κB pathways via the TLR7 signal.

Expert-Level Immunofixation Electrophoresis Image Recognition based on Explainable and Generalizable Deep Learning.

BACKGROUND: Immunofixation electrophoresis (IFE) is important for diagnosis of plasma cell disorders (PCDs). Manual analysis of IFE images is time-consuming and potentially subjective. An artificial intelligence (AI) system for automatic and accurate IFE image recognition is desirable. METHODS: In total, 12 703 expert-annotated IFE images (9182 from a new IFE imaging system and 3521 from an old one) were used to develop and test an AI system that was an ensemble of 3 deep neural networks. The model takes an IFE image as input and predicts the presence of 8 basic patterns (IgA-, IgA-, IgG-, IgG-, IgM-, IgM-, light chain and ) and their combinations. Score-based class activation maps (Score-CAMs) were used for visual explanation of the models prediction. RESULTS: The AI model achieved an average accuracy, sensitivity, and specificity of 99.82, 93.17, and 99.93, respectively, for detection of the 8 basic patterns, which outperformed 4 junior experts with 1 years experience and was comparable to a senior expert with 5 years experience. The Score-CAMs gave a reasonable visual explanation of the prediction by highlighting the target aligned regions in the bands and indicating potentially unreliable predictions. When trained with only the new system images, the models performance was still higher than junior experts on both the new and old IFE systems, with average accuracy of 99.91 and 99.81, respectively. CONCLUSIONS: Our AI system achieved human-level performance in automatic recognition of IFE images, with high explainability and generalizability. It has the potential to improve the efficiency and reliability of diagnosis of PCDs.

A novel mRNA rabies vaccine as a promising candidate for rabies post-exposure prophylaxis protects animals from different rabies viruses.

Rabies, caused by the rabies virus (RABV), is the most fatal zoonotic disease. It is a neglected tropical disease which remains a major public health problem, causing approximately 59,000 deaths worldwide annually. Despite the existence of effective vaccines, the high incidence of human rabies is mainly linked to tedious vaccine immunisation procedures and the overall high cost of post-exposure prophylaxis. Therefore, it is necessary to develop an effective vaccine that has a simple procedure and is affordable to prevent rabies infection in humans. RABV belongs to the genus Lyssavirus and family Rhabdoviridae. Previous phylogenetic analyses have identified seven major clades of RABV in China (China I-VII), confirmed by analysing nucleotide sequences from both the G and N proteins. This study evaluated the immunogenicity and protective capacity of SYS6008, an mRNA rabies vaccine expressing rabies virus glycoprotein, in mice and cynomolgus macaques. We demonstrated that SYS6008 induced sufficient levels of rabies neutralising antibody (RVNA) in mice. In addition, SYS6008 elicited strong and durable RVNA responses in vaccinated cynomolgus macaques. In the pre-exposure prophylaxis murine model, one or two injections of SYS6008 at 1/10 or 1/30 of dosage provided protection against a challenge with a 30-fold LD50 of rabies virus (China I and II clades). We also demonstrated that in the post-exposure prophylaxis murine model, which was exposed to lethal rabies virus (China I-VII clades) before vaccination, one or two injections of SYS6008 at both 1/10 and 1/30 dosages provided better protection against rabies virus challenge than the immunization by five injections of commercial vaccines at the same dosage. In addition, we proved that SYS6008-induced RVNAs could neutralise RABV from the China I-VII clades. Finally, 1/10 of the dosage of SYS6008 was able to stimulate significant RABV-G specificity in the T cell response. Furthermore, we found that SYS6008 induced high cellular immunity, including RABV-G-specific T cell responses and memory B cells. Our results imply that the SYS6008 rabies vaccine, with a much simpler vaccination procedure, better immunogenicity, and enhanced protective capacity, could be a candidate vaccine for post-exposure prophylaxis of rabies infections.

Molecular Karyotyping on Populus simonii × P. nigra and the Derived Doubled Haploid.

The molecular karyotype could represent the basic genetic make-up in a cell nucleus of an organism or species. A doubled haploid (DH) is a genotype formed from the chromosome doubling of haploid cells. In the present study, molecular karyotype analysis of the poplar hybrid Populus simonii × P. nigra (P. xiaohei) and the derived doubled haploids was carried out with labeled telomeres, rDNA, and two newly repetitive sequences as probes by fluorescence in situ hybridization (FISH). The tandem repeats, pPC349_XHY and pPD284_XHY, with high-sequence homology were used, and the results showed that they presented the colocalized distribution signal in chromosomes. For P. xiaohei, pPD284_XHY produced hybridizations in chromosomes 1, 5, 8, and 9 in the hybrid. The combination of pPD284_XHY, 45S rDNA, and 5S rDNA distinctly distinguished six pairs of chromosomes, and the three pairs of chromosomes showed a significant difference in the hybridization between homologous chromosomes. The repeat probes used produced similar FISH hybridizations in the DH; nevertheless, pPD284_XHY generated an additional hybridization site in the telomere region of chromosome 14. Moreover, two pairs of chromosomes showed differential hybridization distributions between homologous chromosomes. Comparisons of the distinguished chromosomes between hybrid and DH poplar showed that three pairs of chromosomes in the DH presented hybridization patterns that varied from those of the hybrid. The No. 8 chromosome in DH and one of the homologous chromosomes in P. xiaohei shared highly similar FISH patterns, which suggested the possibility of intact or mostly partial transfer of the chromosome between the hybrid and DH. Our study will contribute to understanding the genetic mechanism of chromosomal variation in P. xiaohei and derived DH plants.

Relationship of biofilm-forming ability of with swimming motility, twitching motility and virulence gene distribution.

To investigate the relationship of biofilm-forming ability of (PA) with swimming motility, twitching motility and virulence gene distribution. A total of 192 clinical isolates of PA were collected consecutively. Microtiter plate method was used to evaluate the ability to form biofilm. The swimming and twitching motilities were detected by plate method. Polymerase chain reaction (PCR) was used to detect virulence genes. Of the 192 PA clinical isolates, 186 (96.9%) showed biofilm-forming ability. Among them, 36 isolates showed weak biofilm-forming ability, 84 exhibited moderate biofilm-forming ability and 66 showed strong biofilm-forming ability. The diameters of the swimming ring for PA with none biofilm-forming ability, weak biofilm-forming ability, moderate biofilm-forming ability, strong biofilm-forming ability were (9.12±6.76), (18.42±7.51), (19.10±4.77) and respectively. The diameters of the twitching ring for PA in above groups were (8.38±1.50), (17.21±7.42), (18.49±5.62) and respectively. The swimming motility and twitching motility of none biofilm-forming ability group were weaker than biofilm-forming ability groups (all <0.05). Among 192 PA strains, 163 were positive (84.9%), 40 were positive (20.8%), 183 were positive (95.3%), and 189 were positive (98.4%). The positive rate of PA virulence gene , and were different in strains with different biofilm-forming abilities (<0.05). The rate of in the strong biofilm-forming ability group was lower than that in the moderate biofilm-forming ability group (=9.293, <0.01) and the weak biofilm-forming ability group (=9.997, <0.01). The rate of in the strong biofilm-forming ability group was higher than that in the weak biofilm-forming ability group (=10.803, <0.01). Most clinical isolates of PA can form biofilm. Swimming and twitching motilities are related to the formation of biofilm, but not significantly related to strength of biofilm-forming ability. The virulence genes of type Ⅲ secretion system for PA may be related to the biofilm-forming ability.

Characterization of carbapenem-resistant hypervirulent Acinetobacter baumannii strains isolated from hospitalized patients in the mid-south region of China.

BACKGROUND: Acinetobacter baumannii has traditionally been considered an opportunistic pathogen with low virulence. In this study, we characterized the carbapenem-resistant hypervirulent A. baumannii (CR-hvAB) stains isolated from our hospital in mid-south region of China. RESULTS: Blood samples collected between January 2017 and May 2019 were used for virulence experiments and biofilm assays of individual carbapenem-resistant A. baumannii (CR-AB) strains, performed using a Galleria mellonella infection model and crystal violet staining method, respectively. CR-AB isolates that induced high mortality in the G. mellonella infection model were subjected to genotyping, susceptibility testing, and clinical data analysis, and the genetic characterization of these isolates was performed by whole-genome sequencing (WGS). Among the 109 CR-AB clinical strains, the survival rate of G. mellonella larvae infected with 7 (6.4%) CR-AB isolates (number of strains with mortality of 0, 10 and 20% was 4, 1, and 2, respectively), was significantly lower than that of A. baumannii ATCC 19606 (100.0%) and the remaining CR-AB isolates (> 80.0%). Consistent with these results, patients infected with these seven isolates had an average 7-day mortality rate of 42.9%, suggesting that the isolates were CR-hvAB. These seven isolates belonged to four sequence types (STs): ST457, ST195, ST369, and ST2088 (a new ST), and mainly ST457 (n = 4). The results of the biofilm study showed that eight strains had powerful biofilm ability (strong [n = 1] and moderate [n = 7] biofilm producers) including these seven CR-hvAB isolates. CONCLUSIONS: CR-hvAB isolates that induced a high mortality rate were cloned in our hospital, most of which belonged to ST457; thus, monitoring of these strains, particularly ST457, should be strengthened in the future. Meanwhile, A. baumannii, which was isolated from blood specimens and found to powerful biofilm-forming ability, is a probable hvAB isolate.

A retrospective study on Escherichia coli bacteremia in immunocompromised patients: Microbiological features, clinical characteristics, and risk factors for shock and death.

BACKGROUND: To evaluate clinical features, bacterial characteristics, and risk factors for shock and mortality of immunocompromised patients with Escherichia coli bacteremia. METHODS: A nearly 6-year retrospective study of E coli bacteremia in 188 immunocompromised patients at Xiangya Hospital was conducted. Demographic, clinical, and laboratory data were documented. Phylogenetic background and virulence factors of E coli isolates were detected by polymerase chain reaction. Risk factors for shock and mortality were also investigated. RESULTS: Of all 188 E coli isolates, most prevalent virulence factors were fimH (91.0%), followed by traT (68.6%) and iutA (67.0%), while papG allele I, gafD, and cdtB were not detected. Phylogenetic group D was dominant (42.0%) among all isolates, and group B2 accounted for 17.6%, while group A and B1 accounted for 28.2% and 12.2%, respectively. In univariate analysis, ibeA and cnf1 were associated with mortality, which were not found in multivariate regression analysis. 22.3% of patients suffered shock, and 30-day mortality rate was 21.3%. MDR (HR 2.956; 95% CI, 1.091-8.012) was the only risk factor for shock, while adult (HR 0.239; 95% CI, 0.108-0.527) was a protective factor. Multivariate analysis revealed that shock (HR 4.268; 95% CI, 2.208-8.248; P < .001) and Charlson index > 2 (HR 2.073; 95% CI, 1.087-3.952; P = .027) were associated with fatal outcome. CONCLUSIONS: Escherichia coli bacteremia was highly lethal in immunocompromised patients, and host-related factors played major roles in poor prognosis, while bacterial determinants had little effect on outcome. This study also provided additional information about the virulence and phylogenetic group characteristics of E coli bacteremia.

Isolation and characterization of a sequence type 25 carbapenem-resistant hypervirulent Klebsiella pneumoniae from the mid-south region of China.

BACKGROUND: The molecular characterization of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) isolates is not well studied. Our goal was to investigate the molecular epidemiology of CR-hvKP strains that were isolated from a Chinese hospital. RESULTS: All clinical carbapenem-resistant K. pneumoniae (CR-KP) isolates were collected and identified from patient samples between 2014 and 2017 from a Chinese hospital. The samples were subjected to screening for CR-hvKP by string test and the detection of the aerobactin gene. CR-hvKP isolates were further confirmed through neutrophil phagocytosis and a mice lethality assay. The CR-hvKP isolates were investigated for their capsular genotyping, virulence gene profiles, and the expression of carbapenemase genes by PCR and DNA sequencing. Multilocus sequence type (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to exclude the homology of these isolates. Twenty strains were identified as CR-hvKP. These strains were resistant to imipenem and several other antibiotics, however, most were susceptible to amikacin. Notably, two isolates were not susceptible to tigecycline. Capsular polysaccharide synthesis genotyping revealed that 17 of the 20 CR-hvKP strains belonged to the K2 serotype, while the others belonged to serotypes other than K1, K2, K5, K20, and K57. The strains were found to be positive for 10 types of virulence genes and a variety of these genes coexisted in the same strain. Two carbapenemase genes were identified: blaKPC-2 (13/20) and blaNDM-1 (1/20). PFGE typing revealed eight clusters comprising isolates that belonged to MLST types ST25, ST11 and ST375, respectively. PFGE cluster A was identified as the main cluster, which included 11 isolates that belong to ST25 and mainly from ICU department. CONCLUSIONS: Our findings suggest that hospital-acquired infections may contribute in part to the CR-hvKP strains identified in this study. It also suggests that ST25 CR-hvKP strain has a clonal distribution in our hospital. Therefore, effective surveillance and strict infection control strategies should be implemented to prevent outbreak by CR-hvKP strains in hospitals setting.

A CpG oligodeoxynucleotide enhances the immune response to rabies vaccination in mice.

BACKGROUND: Rabies is a fatal disease that is preventable when post exposure prophylaxis (PEP) is administered in a timely fashion. CpG oligodeoxynucleotides (ODNs) can trigger cells that express Toll-like receptor 9, and their immunopotentiation activity in an inactivated aluminum-adjuvanted rabies vaccine for dogs has been identified using mouse and dog models. METHODS: A human diploid cell rabies vaccine (HDCV) of humans and a CpG ODNs with cross-immunostimulatory activity in humans and mice were used to evaluate the immunogenicity and protective efficacy of CpG ODN in a mouse model that simulates human PEP. RESULTS: HDCV combined with CpG ODN (HDCV-CpG) stimulated mice to produce rabies virus-specific neutralizing antibody (RVNA) earlier and increased the seroconversion rate. Compared with HDCV alone, either HDCV-1.25 µg CpG or HDCV-5 µg CpG increased the levels of RVNA. In particular, 5 µg CpG ODN per mouse significantly boosted the levels of RVNA compared with HDCV alone. IFN-γ producing splenocytes generated in the HDCV-5 µg CpG group were significantly increased compared to the group treated with HDCV alone. When the immunization regimen was reduced to three injections or the dose was reduced to half of the recommended HDCV combined with CpG ODN, the RVNA titers were still higher than those induced by HDCV alone. After viral challenge, 50% of mice immunized with a half-dose HDCV-CpG survived, while the survival rate of mice immunized with HDCV alone was 30%. CONCLUSIONS: The immunopotentiation activity of CpG ODNs for a commercially available human rabies vaccine was first evaluated in a mouse model on the basis of the Essen regimen. Our results suggest that the CpG ODN used in this study is a potential adjuvant to rabies vaccines for human use.

Role of systemic injection of rabies immunoglobulin in rabies vaccination.

To determine the role of systemic injection of rabies immunoglobulin (RIG) in rabies vaccination, we analyzed the level of antibody against rabies virus in the serum of mice that received various doses of RIG combined with rabies vaccine. Our results indicate that systemic injection of RIG does not contribute detectably to passive or adaptive immunization, suggesting that the main function of RIG in individuals with category III exposure is to neutralize rabies virus via immediate local infiltration of the wound.

Comparison of genotypes I and III in Japanese encephalitis virus reveals distinct differences in their genetic and host diversity.

UNLABELLED: Japanese encephalitis (JE) is an arthropod-borne disease associated with the majority of viral encephalitis cases in the Asia-Pacific region. The causative agent, Japanese encephalitis virus (JEV), has been phylogenetically divided into five genotypes. Recent surveillance data indicate that genotype I (GI) is gradually replacing genotype III (GIII) as the dominant genotype. To investigate the mechanism behind the genotype shift and the potential consequences in terms of vaccine efficacy, human cases, and virus dissemination, we collected (i) all full-length and partial JEV molecular sequences and (ii) associated genotype and host information comprising a data set of 873 sequences. We then examined differences between the two genotypes at the genetic and epidemiological level by investigating amino acid mutations, positive selection, and host range. We found that although GI is dominant, it has fewer sites predicted to be under positive selection, a narrower host range, and significantly fewer human isolates. For the E protein, the sites under positive selection define a haplotype set for each genotype that shows striking differences in their composition and diversity, with GIII showing significantly more variety than GI. Our results suggest that GI has displaced GIII by achieving a replication cycle that is more efficient but is also more restricted in its host range. IMPORTANCE: Japanese encephalitis is an arthropod-borne disease associated with the majority of viral encephalitis cases in the Asia-Pacific region. The causative agent, Japanese encephalitis virus (JEV), has been divided into five genotypes based on sequence similarity. Recent data indicate that genotype I (GI) is gradually replacing genotype III (GIII) as the dominant genotype. Understanding the reasons behind this shift and the potential consequences in terms of vaccine efficacy, human cases, and virus dissemination is important for controlling the spread of the virus and reducing human fatalities. We collected all available full-length and partial JEV molecular sequences and associated genotype and host information. We then examined differences between the two genotypes at the genetic and epidemiological levels by investigating amino acid mutations, positive selection, and host range. Our results suggest that GI has displaced GIII by achieving a replication cycle that is more efficient but more restricted in host range.

Distribution and phylogenetic analysis of Culex flavivirus in mosquitoes in China.

Culex flavivirus (CxFV) is an insect-specific virus of the genus Flavivirus. CxFV strains have been isolated from Cx. pipiens, Cx. quinquefasciatus, and other Cx. species in Asia, Africa, North America, Central America and South America. CxFV was isolated for the first time in China in 2006. As this is a novel flavivirus, we explored the distribution and genetic characteristics of Culex flavivirus in China. A total of 46,649 mosquitoes were collected in seven provinces between 2004 and 2012 and were analysed in 871 pools. 29 CxFV RNAs from Cx. pipiens, Cx. tritaeniorhynchus, Anopheles Sinensis, and Culex spp. tested positive for CxFV in real-time RT-PCR. 6 CxFV strains were isolated from Cx. species collected in Shandong, Henan, and Shaanxi provinces, while no virus or viral RNA was detected in samples from Sichuan, Chongqing, Hubei, and Fujian. Phylogenetic analysis of the envelope gene indicated that Chinese strains formed a robust subgroup of genotype 1, together with viruses from the United States and Japan. This study demonstrates that the geographic distribution of CxFV in China is widespread, but geographical boundaries to spread are apparent. Our findings suggest that CxFV can infect various mosquito species in nature.

Molecular epidemiology of reemergent rabies in Yunnan Province, southwestern China.

Yunnan Province in China borders 3 countries (Vietnam, Laos, and Myanmar) in Southeast Asia. In the 1980s, a large-scale rabies epidemic occurred in this province, which subsided by the late 1990s. However, 3 human cases of rabies in 2000 indicated reemergence of the disease in 1 county. In 2012, rabies was detected in 77 counties; 663 persons died of rabies during this new epidemic. Fifty two rabies virus strains obtained during 2008-2012 were identified and analyzed phylogenetically by sequencing the nucleoprotein gene. Of the 4 clades identified, clades YN-A and YN-C were closely related to strains from neighboring provinces, and clade YN-B was closely related to strains from Southeast Asia, but formed a distinct branch. Rabies virus diversity might be attributed to dog movements among counties, provinces, and neighboring countries. These findings suggest that Yunnan Province is a focal point for spread of rabies between Southeast Asia and China.

Met-CCL5 represents an immunotherapy strategy to ameliorate rabies virus infection.

BACKGROUND: Infection of rabies virus (RABV) causes central nervous system (CNS) dysfunction and results in high mortality in human and animals. However, it is still unclear whether and how CNS inflammation and immune response contribute to RABV infection. METHODS: Suckling mice were intracerebrally infected with attenuated RABV aG and CTN strains, followed by examination of chemokine or cytokine production, inflammatory cell infiltration and neuron apoptosis in the brain. Furthermore, the suckling mice and adult mice that were intracerebrally infected with aG and the adult mice that were intramuscularly infected with street RABV HN10 were treated with CCL5 antagonist (Met-CCL5) daily beginning on day 2 postinfection. The survival rates and inflammation responses in the CNS of these mice were analyzed. RESULTS: Excessive CCL5 in the CNS was associated with CNS dysfunction, inflammation, and macrophage or lymphocyte infiltration after attenuated or street RABV infection. Administration of exogenous CCL5 induced excessive infiltration of immune cells into the CNS and enhanced inflammatory chemokine and cytokine production. Met-CCL5 treatment significantly prolonged survival time of the suckling mice inoculated with aG and adult mice infected with aG and HN10. CONCLUSIONS: These results suggest that CCL5 in the CNS is a key regulator involved in inducing rabies encephalomyelitis. Furthermore, treatment with the CCL5 antagonist Met-CCL5 prolongs survival time of the mice infected with attenuated or street RABVs, which might represent a novel therapeutic strategy to ameliorate RABV infection.

Human rabies surveillance and control in China, 2005-2012.

BACKGROUND: Rabies reemerged in China during the 1990s with a gradual increase in the number and geographical dispersion of cases. As a consequence, a national surveillance program was introduced in 2005 to investigate the outbreak in terms of vaccination coverage, PEP treatment, and geographical and social composition. METHODS: The surveillance program was coordinated at the national level by the Chinese Center for Disease Control (CCDC) with data collected by regional health centres and provincial CCDCs, and from other official sources. Various statistical and multivariate analysis techniques were then used to evaluate the role and significance of implemented policies and strategies related to rabies prevention and control over this period. RESULTS: From 2005-2012, 19,221 cases were reported across 30 provinces, but these primarily occurred in rural areas of southern and eastern China, and were predominantly associated with farmers, students and preschool children. In particular, detailed analysis of fatalities reported from 2010 to 2011 shows they were associated with very low rates of post exposure treatment compared to the cases with standard PEP. Nevertheless, regulation of post-exposure prophylaxis quality, together with improved management and vaccination of domesticated animals, has improved prevention and control of rabies. CONCLUSIONS: The various control policies implemented by the government has played a key role in reducing rabies incidences in China. However, level of PEP treatment varies according to sex, age, degree and site of exposure, as well as the source of infection. Regulation of PEP quality together with improved management and vaccination of domesticated animals have also helped to improve prevention and control of rabies.

Identification of animal rabies in Inner Mongolia and analysis of the etiologic characteristics.

OBJECTIVE: To perform pathological observation and etiological identification of specimens collected from dairy cows, beef cattle and dogs which were suspected of rabies in Inner Mongolia in 2011, and analyze their etiological characteristics. METHODS: Pathological observation was conducted on the brain specimens of three infected animals with Hematoxylin-Eosin staining, followed by confirmation using immunofluorescence and nested RT-PCR methods. Finally, phylogenetic analysis was conducted using the virus N gene sequence amplified from three specimens. RESULTS: Eosinophilic and cytoplasmic inclusion bodies were seen in neuronal cells of the CNS; and rabies non-characteristic histopathological changes were also detected in the CNS. The three brain specimens were detected positive. N gene nucleotide sequence of these three isolates showed distinct sequence identity, therefore they fell into different groups in the phylogenetic analysis. N gene in the cow and dog had higher homology with that in Hebei isolate, but that in the beef cattle had higher homology with that in Mongolian lupine isolate and Russian red fox isolate. CONCLUSION: Rabies were observed in the dairy cow, beef cattle and canine in the farm in Inner Mongolia, in 2011, which led to a different etiologic characteristics of the epidemic situation.

Examining the relationship between international digital trade, green technology innovation and environmental sustainability in top emerging economics.

Ensuring preserving a sustainable environment is a crucial concern for individuals worldwide. In previous research, CO2 emissions have been used to measure environmental deterioration. However, in this study, we have expanded the scope to include carbon emissions and several other gases. This comprehensive measure is referred to as the ecological footprint (EFP). More significant international digital trade (IDT) has the potential to achieve several positive results, including reducing EFP (economic frictions and barriers), stimulating economic growth, and minimizing trade risk and volatility. These benefits can be realized by implementing structural reforms in significant production and development sectors. Green technology innovation (GTI) has the potential to make substantial progress in ecological quality and energy efficiency. Nevertheless, previous studies still need to adequately prioritize examining rising economies in terms of international trade diversification and GTI. This study examined the effects of IDT, GTI, and renewable energy consumption (REC) on EFP in BRICST countries. The study utilized data from the period between 1995 and 2022. The cross-sectionally augmented autoregressive distributed lag (CS-ARDL) model demonstrates that EFP negatively correlates with trade diversification, REC, and GTI in the long and short term. These countries have demonstrated a significant presence of eco-friendly products in their trade portfolios, and their manufacturing processes are shifting towards GTI. The objective is to enhance the REC sources and minimize EFP from consumption. Conversely, the increasing economic growth within this economic group has a compounding impact on the environment's decline since it amplifies the carbon emissions from increased consumption. To reduce the EFP level, the paper suggests increasing investment in GTI, promoting worldwide digital trade, and embracing renewable energy sources.

Resveratrol inhibits rabies virus infection in N2a cells by activating the SIRT1/Nrf2/HO-1 pathway.

Rabies is a highly lethal infectious disease with no existing treatment available, thus investigating effective antiviral compounds to control rabies virus (RABV) infection is of utmost importance. Resveratrol is a natural phenolic compound that, as a phytoalexin, exhibits several biological activities, including antiviral activity. In this study, we evaluated the inhibitory effect of resveratrol on RABV infection and investigated its molecular antiviral mechanism. We found that resveratrol significantly inhibited RABV infection, including the phases of adsorption, replication, and release, and also directly inactivated RABV and inhibited its infectivity. However, resveratrol had no significant effect on RABV internalization. Resveratrol also reduced RABV-induced oxidative stress, specifically reactive oxygen species and malondialdehyde levels. Western blotting analysis revealed that resveratrol enhanced antioxidant signaling via the SIRT1/Nrf2/HO-1 pathway and inhibited viral replication. Viral infection was enhanced after SIRT1 knockdown, which inhibited the SIRT1/Nrf2/HO-1 antioxidant signaling pathway, suggesting that this pathway plays an important role in RABV replication. Overall, resveratrol prevented the adsorption, replication, and release of RABV and directly inactivated RABV, but failed to inhibit RABV internalization. Furthermore, resveratrol activated the SIRT1/Nrf2/HO-1 pathway to inhibit RABV replication and suppressed RABV-induced oxidative stress. These findings highlight the therapeutic potential of resveratrol for fighting RABV infections.