Nonstructural Protein NSs Activates Inflammasome and Pyroptosis through Interaction with NLRP3 in Human Microglial Cells Infected with Severe Fever with Thrombocytopenia Syndrome Bandavirus.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne febrile disease caused by SFTS virus (SFTSV), or Dabie bandavirus, in the Phenuiviridae family. Clinically neurological disorders in SFTS have been commonly reported, but their neuropathogenesis has rarely been studied. Microglia are a type of neuroglia accounting for 10 to 12% of all cells in the brain. As resident immune cells, microglial cells are the first line of immune defense present in the central nervous system (CNS). Here, we report that SFTSV was able to infect microglial cells and stimulate interleukin 1ß (IL-1ß) secretion in the brains of infected neonatal BALB/c mice. We characterized the cell death induced in infected human microglial HMC3 cells, also susceptible to SFTSV, and found that the NOD-like receptor protein 3 (NLRP3) inflammasome was activated, leading to secretion of IL-1ß and pyroptosis. Knockdown of NLRP3 or inhibition of the NLRP3 inflammasome activation suppressed the viral replication, suggesting that the activation of the NLRP3 inflammasome may support SFTSV replication in microglial cells. Viral nonstructural protein NSs, a known modulator of immune responses, interacted and colocalized with NLRP3 for the inflammasome activation. It appeared that the N-terminal fragment, amino acids 1 to 66, of NSs was critical to promote the assembly of the inflammasome complex by interacting with NLRP3 for its activation in microglial cells. Our findings provide evidence that SFTSV may cause neurological disorders through infecting microglia and activating the inflammasome through its nonstructural protein NSs for neural cell death and inflammation. This study may have revealed a novel mechanism of SFTSV NSs in dysregulating host response. IMPORTANCE Encephalitis or encephalopathy during severe fever with thrombocytopenia syndrome (SFTS) is considered a critical risk factor leading to high mortality, but there have been no studies to date on the pathogenesis of encephalitis or encephalopathy caused by SFTS virus. Here, we report that SFTSV infection can active the NLRP3 inflammasome and induce IL-1ß secretion in the brains of infected newborn mice. In infected human HMC3 microglia, SFTSV activated the NLRP3 inflammasome via the viral nonstructural protein NSs through interaction with its N-terminal fragment. Notably, our findings suggest that the activation of the NLRP3 inflammasome may promote SFTSV replication in infected microglial cells. This study may reveal a novel mechanism by SFTSV to dysregulate host responses through its nonstructural protein, which could help us understand viral neuropathogenesis in SFTS patients.

Lifestyle-based nomogram for identifying the Chaoshan inhabitants of China at high risk of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (HP) infection is associated with various diseases. Early detection can prevent the onset of illness. We constructed a nomogram to predict groups at high risk of HP infection. METHODS: Patients who underwent regular medical check-ups at hospital in Chaoshan, China from March to September 2022 were randomly allocated to the training and validation cohorts. Risk factors including basic characteristics and lifestyle habits associated with HP infection were analyzed by logistic regression analyses. The independent varieties were calculated and plotted into a nomogram. The nomogram was internally validated by receiver operating characteristic curve, calibration, and decision curve analyses (DCAs). RESULTS: Of the 945 patients, 680 were included in the training cohort and 265 in the validation cohort. 356 patients in training cohort with positive 13 C-UBT results served as the infected group, and 324 without infection were the control group. The multivariate regression analyses showed that the risk factors for HP infection included alcohol consumption (OR = 1.29, 95%CI = 0.78-2.13, P = 0.03), family history of gastric disease (OR = 4.35, 95%CI = 1.47-12.84, P = 0.01), living with an HP-positive individual (OR = 18.09, 95%CI = 10.29-31.82, P < 0.0001), drinking hot tea (OR = 1.58, 95%CI = 1.05-2.48, P = 0.04), and infection status of co-drinkers unknown (OR = 2.29, 95%CI = 1.04-5.06, P = 0.04). However, drinking tea > 3 times per day (OR = 0.56, 95%CI = 0.33-0.95, P = 0.03), using serving chopsticks (OR = 0.30, 95%CI = 0.12-0.49, P < 0.0001) were protective factors for HP infection. The nomogram had an area under the curve (AUC) of 0.85 in the training cohort. The DCA was above the reference line within a large threshold range, indicating that the model was better. The calibration analyses showed the actual occurrence rate was basically consistent with the predicted occurrence rate. The model was validated in the validation cohort, and had a good AUC (0.80), DCA and calibration curve results. CONCLUSIONS: This nomogram, which incorporates basic characteristics and lifestyle habits, is an efficient model for predicting those at high risk of HP infection in the Chaoshan region.

Monoclonal antibody targeting a novel linear epitope on nucleoprotein confers pan-reactivity to influenza A virus.

Nucleoprotein (NP) functions crucially in the replicative cycle of influenza A virus (IAV) via forming the ribonucleoprotein complex together with PB2, PB1, and PA proteins. As its high conservation, NP ranks one of the hot targets for design of universal diagnostic reagents and antiviral drugs for IAV. Here, we report an anti-NP murine monoclonal antibody (mAb) 5F10 prepared from traditional lymphocyte hybridoma technique with the immunogen of a clade 2.3.4.4 H5N1 subtype avian influenza virus. The specificity of mAb 5F10 to NP protein was confirmed by immunofluorescence assay and western blotting, and the mAb 5F10 could be used in immunoprecipitation and immunohistochemistry assays. Importantly, mAb 5F10 possessed broad-spectrum reactivity against H1~H11 subtypes of avian influenza viruses, including various HA clades of H5Nx subtype. In addition, mAb 5F10 also showed good affinity with H1N1 and H3N2 subtype influenza viruses of swine and human origin. Furthermore, the recognized antigenic epitope of mAb 5F10 was identified to consist of the conserved amino acid motif 81EHPSA85 in the second flexible loop region of NP protein through screening the phage display peptide library. Collectively, the mAb 5F10 which recognizes the novel universal NP linear B-cell epitope of IAV with diverse origins and subtypes will be a powerful tool for NP protein-based structural, functional, and mechanistic studies, as well as the development of detection methods and universal vaccines for IAV. KEY POINTS: • A broad-spectrum mAb against various subtypes and sources of IAV was developed • The mAb possessed good reactivity in IFA, western blot, IP, and IHC assays • The mAb targeted a novel conserved linear B-cell epitope involving 81EHPSA85 on NP protein.

The role of single-cell RNA sequencing in cardiac tumour - a case report.

A 65-year-old woman presented to our hospital with 5 days of chest tightness, dyspnoea, and lower abdominal distension. Echocardiography revealed a mass in the right atrium. An emergency operation was carried out to prevent tumour shedding. The patient was discharged on the 4th day of tumour resection, without any complications At the 18 months follow-up, she suffered from kidney and lung tumours. She refused any treatment and passed away. scRNA-seq was applied to analyse the nature of the tumour. The cellular components of benign tumours include chondrocytes, smooth muscle cells, fibroblasts, mesenchymal stromal cells, and osteoblasts. Additionally, the cyclic guanosine monophosphate (cGMP-PKG) signalling pathway, transcriptional misregulation in cancer, and the p53 signalling pathway may be related to the growth of this tumour. scRNA-seq is a good approach to analyse growth patterns of cardiac tumours and helpful for distinguishing the nature of the tumour.

Pirfenidone ameliorates silica-induced lung inflammation and fibrosis in mice by inhibiting the secretion of interleukin-17A.

Silicosis is a global occupational disease characterized by lung dysfunction, pulmonary inflammation, and fibrosis, for which there is a lack of effective drugs. Pirfenidone has been shown to exert anti-inflammatory and anti-fibrotic properties in the lung. However, whether and how pirfenidone is effective against silicosis remains unknown. Here, we evaluated the efficacy of pirfenidone in the treatment of early and advanced silicosis in an experimental mouse model and explored its potential pharmacological mechanisms. We found that pirfenidone alleviated silica-induced lung dysfunction, secretion of inflammatory cytokines (TNF-α, IL-1ß, IL-6) and deposition of fibrotic proteins (collagen I and fibronectin) in both early and advanced silicosis models. Moreover, we observed that both 100 and 200 mg/kg pirfenidone can effectively treat early-stage silicosis, while 400 mg/kg was recommended for advanced silicosis. Mechanistically, antibody array and bioinformatic analysis showed that the pathways related to IL-17 secretion, including JAK-STAT pathway, Th17 differentiation, and IL-17 pathway, might be involved in the treatment of silicosis by pirfenidone. Further in vivo experiments confirmed that pirfenidone reduced the production of IL-17A induced by silica exposure via inhibiting STAT3 phosphorylation. Neutralizing IL-17A by anti-IL-17A antibody improved lung function and reduced pulmonary inflammation and fibrosis in silicosis animals. Collectively, our study has demonstrated that pirfenidone effectively ameliorated silica-induced lung dysfunction, pulmonary inflammation and fibrosis in mouse models by inhibiting the secretion of IL-17A.

Tetrandrine alleviates silicosis by inhibiting canonical and non-canonical NLRP3 inflammasome activation in lung macrophages.

Silicosis caused by inhalation of silica particles leads to more than ten thousand new occupational exposure-related deaths yearly. Exacerbating this issue, there are currently few drugs reported to effectively treat silicosis. Tetrandrine is the only drug approved for silicosis treatment in China, and despite more than decades of use, its efficacy and mechanisms of action remain largely unknown. Here, in this study, we established silicosis mouse models to investigate the effectiveness of tetrandrine of early and late therapeutic administration. To this end, we used multiple cardiopulmonary function test, as well as markers for inflammation and fibrosis. Moreover, using single cell RNA sequencing and transcriptomics of lung tissue and quantitative microarray analysis of serum from silicosis and control mice, our results provide a novel description of the target pathways for tetrandrine. Specifically, we found that tetrandrine attenuated silicosis by inhibiting both the canonical and non-canonical NLRP3 inflammasome pathways in lung macrophages. Taken together, our work showed that tetrandrine yielded promising results against silicosis-associated inflammation and fibrosis and further lied the groundwork for understanding its molecular targets. Our results also facilitated the wider adoption and development of tetrandirne, potentially accelerating a globally accepted therapeutic strategy for silicosis.

PSPS: A Step toward Tamper Resistance against Physical Computer Intrusion.

Cyberattacks are increasing in both number and severity for private, corporate, and governmental bodies. To prevent these attacks, many intrusion detection systems and intrusion prevention systems provide computer security by monitoring network packets and auditing system records. However, most of these systems only monitor network packets rather than the computer itself, so physical intrusion is also an important security issue. Furthermore, with the rapid progress of the Internet of Things (IoT) technology, security problems of IoT devices are also increasing. Many IoT devices can be disassembled for decompilation, resulting in the theft of sensitive data. To prevent this, physical intrusion detection systems of the IoT should be considered. We here propose a physical security system that can protect data from unauthorized access when the computer chassis is opened or tampered with. Sensor switches monitor the chassis status at all times and upload event logs to a cloud server for remote monitoring. If the system finds that the computer has an abnormal condition, it takes protective measures and notifies the administrator. This system can be extended to IoT devices to protect their data from theft.

Suppression of the IFN-α and -ß Induction through Sequestering IRF7 into Viral Inclusion Bodies by Nonstructural Protein NSs in Severe Fever with Thrombocytopenia Syndrome Bunyavirus Infection.

Induction of type I IFNs during viral infection is crucial for host defense. IRF 3 and IRF7 play a critical role as key transcription factors in the activation of the IFN induction. Viruses have evolved a variety of strategies to evade innate immunity. Our previous studies have shown that the nonstructural protein (NSs) of the severe fever with thrombocytopenia syndrome virus (SFTSV) can suppress the IFN-ß induction through its interaction with tank-binding kinase-1 and sequestering the inhibitor of nuclear factor kappa B kinase(IKK) complex into the inclusion bodies formed by NSs. In this study, we characterized the unique function of IRF7 in innate immunity and its role in inducing IFN-α in particular, regulated by NSs during the SFTSV infection in several cell types of human origin. Whereas IRF3 is constitutively expressed, IRF7 was significantly induced differentially in various cell types in response to SFTSV infection, promoted the induction of IFN-α2 and -α4, and further induced IFN-ß, thus contributing to suppressing the viral replication. Our data indicate that NSs directly interacted with and sequestered IRF7 into the inclusion bodies, which is different from IRF3 indirectly interacting with NSs. Although interaction of NSs with IRF7 did not inhibit IRF7 phosphorylation, p-IRF7 was trapped in the inclusion bodies, resulting in a significant reduction of the IFN-α2 and -α4 induction and therefore enhanced viral replication. Interaction of the viral NSs with both IRF7 and IRF3 and subsequent sequestration of these transcription factors into viral inclusion bodies, a unique strategy used by this phlebovirus, may ensure effective evasion and suppression of host innate immunity.

Biological features of novel avian influenza A (H7N9) virus.

Human infection associated with a novel reassortant avian influenza H7N9 virus has recently been identified in China. A total of 132 confirmed cases and 39 deaths have been reported. Most patients presented with severe pneumonia and acute respiratory distress syndrome. Although the first epidemic has subsided, the presence of a natural reservoir and the disease severity highlight the need to evaluate its risk on human public health and to understand the possible pathogenesis mechanism. Here we show that the emerging H7N9 avian influenza virus poses a potentially high risk to humans. We discover that the H7N9 virus can bind to both avian-type (α2,3-linked sialic acid) and human-type (α2,6-linked sialic acid) receptors. It can invade epithelial cells in the human lower respiratory tract and type II pneumonocytes in alveoli, and replicated efficiently in ex vivo lung and trachea explant culture and several mammalian cell lines. In acute serum samples of H7N9-infected patients, increased levels of the chemokines and cytokines IP-10, MIG, MIP-1ß, MCP-1, IL-6, IL-8 and IFN-α were detected. We note that the human population is naive to the H7N9 virus, and current seasonal vaccination could not provide protection.

DNA Encountering Terbium(III): A Smart "Chemical Nose/Tongue" for Large-Scale Time-Gated Luminescent and Lifetime-Based Sensing.

Recent years have witnessed the rapid development of pattern-based sensors due to their potential to detect and differentiate a wealth of analytes with only few probes. However, no one has found or used the combination of DNA and terbium(III) (Tb) as a pattern recognition system for large-scale mix-and-measure assays. Here we report for the first time that DNA-sensitized Tb (DNA/Tb), as a label-free and versatile "chemical nose/tongue", can be employed for wide-scale time-gated luminescent (TGL) monitoring of metal ions covering nearly the entire periodic table in a cost-effective fashion. A series of guanine/thymine (G/T)-rich DNA ligands was screened to sensitize the luminescence of Tb (referring to the antenna effect) as smart pattern responders to metal ions in solution, and metal ion-DNA interactions can differentially alter the antenna effect of DNA toward Tb as pattern signals. Our results show that as few as 3 DNA/Tb label-free sensors could successfully discriminate 49 analytes, including alkali-metal ions, alkaline-earth-metal ions, transition/post-transition metal ions, and lanthanide ions. A blind test with 49 metals further confirmed the discriminating power of DNA/Tb sensors. Moreover, the lifetime-based pattern recognition application using DNA/Tb sensors was also demonstrated. This DNA/Tb pattern recognition strategy could be extended to construct a series of "chemical noses/tongues" for monitoring various biochemical species by using different responsive DNA ligands, thus promising a versatile and powerful tool for a sensing application and investigation of DNA-involving molecular interactions.

Ultrasensitive specific terahertz sensor based on tunable plasmon induced transparency of a graphene micro-ribbon array structure.

We proposed an ultrasensitive specific terahertz sensor consisting of two sets of graphene micro-ribbon with different widths. The interference between the plasmon resonances of the wide and narrow graphene micro-ribbons gives rise to the plasmon induced transparency (PIT) effect and enables ultrasensitive sensing in terahertz region. The performances of the PIT sensor have been analyzed in detail considering the thickness and refractive index sensing applications using full wave electromagnetic simulations. Taking advantage of the electrical tunability of graphene's Fermi level, we demonstrated the specific sensing of benzoic acid with detection limit smaller than 6.35 µg/cm2. The combination of specific identification and enhanced sensitivity of the PIT sensor opens exciting prospects for bio/chemical molecules sensing in the terahertz region.

Co-circulation of multiple genotypes of influenza A (H7N9) viruses in eastern China, 2016-2017.

Five epidemic waves of human infection with influenza A (H7N9) virus have emerged in China since spring 2013. We previously described the epidemiological characterization of the fifth wave in Jiangsu province. In this study, 41 H7N9 viruses from patients and live-poultry markets were isolated and sequenced to further elucidate the genetic features of viruses of the fifth wave in Jiangsu province. Phylogenetic analysis revealed substantial genetic diversity in the internal genes, and 18 genotypes were identified from the 41 H7N9 virus strains. Furthermore, our data revealed that 41 isolates from Jiangsu contained the G186V and Q226L/I mutations in their haemagglutinin (HA) protein, which may increase the ability of these viruses to bind the human receptor. Four basic amino acid insertions were not observed in the HA cleavage sites of 167 H7N9 viruses from Jiangsu, which revealed that highly pathogenic avian influenza (HPAI) H7N9 viruses did not spread to Jiangsu province in the fifth wave. These findings revealed that multiple genotypes of H7N9 viruses co-circulated in the fifth wave in Jiangsu province, which indicated that the viruses have undergone ongoing evolution with genetic mutation and reassortment. Our study highlights the need to constantly monitor the evolution of H7N9 viruses and reinforce systematic influenza surveillance of humans, birds, and pigs in China.

On the inherent properties of Soluplus and its application in ibuprofen solid dispersions generated by microwave-quench cooling technology.

Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, or Soluplus®, is a relatively new copolymer and a promising carrier of amorphous solid dispersions. Knowledge on the inherent properties of Soluplus® (e.g. cloud points, critical micelle concentrations, and viscosity) in different conditions is relatively inadequate, and the application characteristics of Soluplus®-based solid dispersions made by microwave methods still need to be clarified. In the present investigation, the inherent properties of a Soluplus® carrier, including cloud points, critical micelle concentrations, and viscosity, were explored in different media and in altered conditions. Ibuprofen, a BCS class II non-steroidal anti-inflammatory drug, was selected to develop Soluplus®-based amorphous solid dispersions using the microwave-quench cooling (MQC) method. Scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Raman spectroscopy (RS), and Fourier transform infrared spectroscopy (FT-IR) were adopted to analyze amorphous properties and molecular interactions in ibuprofen/Soluplus® amorphous solid dispersions generated by MQC. Dissolution, dissolution extension, phase solubility, equilibrium solubility, and supersaturated crystallization inhibiting experiments were performed to elucidate the effects of Soluplus® on ibuprofen in solid dispersions. This research provides valuable information on the inherent properties of Soluplus® and presents a basic understanding of Soluplus® as a carrier of amorphous solid dispersions.

The Influence of Cellulosic Polymer's Variables on Dissolution/Solubility of Amorphous Felodipine and Crystallization Inhibition from a Supersaturated State.

The collective impact of cellulosic polymers on the dissolution, solubility, and crystallization inhibition of amorphous active pharmaceutical ingredients (APIs) is still far from being adequately understood. The goal of this research was to explore the influence of cellulosic polymers and incubation conditions on enhancement of solubility and dissolution of amorphous felodipine, while inhibiting crystallization of the drug from a supersaturated state. Variables, including cellulosic polymer type, amount, ionic strength, and viscosity, were evaluated for effects on API dissolution/solubility and crystallization processes. Water-soluble cellulosic polymers, including HPMC E15, HPMC E5, HPMC K100-LV, L-HPC, and MC, were studied. All cellulosic polymers could extend API dissolution and solubility to various extents by delaying crystallization and prolonging supersaturation duration, with their effectiveness ranked from greatest to least as HPMC E15 > HPMC E5 > HPMC K100-LV > L-HPC > MC. Decreased polymer amount, lower ionic strength, or higher polymer viscosity tended to decrease dissolution/solubility and promote crystal growth to accelerate crystallization. HPMC E15 achieved greatest extended API dissolution and maintenance of supersaturation from a supersaturated state; this polymer thus had the greatest potential for maintaining sustainable API absorption within biologically relevant time frames.

Synaptogyrin-2 Promotes Replication of a Novel Tick-borne Bunyavirus through Interacting with Viral Nonstructural Protein NSs.

Synaptogyrin-2 is a non-neuronal member of the synaptogyrin family involved in synaptic vesicle biogenesis and trafficking. Little is known about the function of synaptogyrin-2. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease characterized by high fever, thrombocytopenia, and leukocytopenia with high mortality, caused by a novel tick-borne phlebovirus in the family Bunyaviridae. Our previous studies have shown that the viral nonstructural protein NSs forms inclusion bodies (IBs) that are involved in viral immune evasion, as well as viral RNA replication. In this study, we sought to elucidate the mechanism by which NSs formed the IBs, a lipid droplet-based structure confirmed by NSs co-localization with perilipin A and adipose differentiation-related protein (ADRP). Through a high throughput screening, we identified synaptogyrin-2 to be highly up-regulated in response to SFTS bunyavirus (SFTSV) infection and to be a promoter of viral replication. We demonstrated that synaptogyrin-2 interacted with NSs and was translocated into the IBs, which were reconstructed from lipid droplets into large structures in infection. Viral RNA replication decreased, and infectious virus titers were lowered significantly when synaptogyrin-2 was silenced in specific shRNA-expressing cells, which correlated with the reduced number of the large IBs restructured from regular lipid droplets. We hypothesize that synaptogyrin-2 is essential to promoting the formation of the IBs to become virus factories for viral RNA replication through its interaction with NSs. These findings unveil the function of synaptogyrin-2 as an enhancer in viral infection.

Delivering siRNA and Chemotherapeutic Molecules Across BBB and BTB for Intracranial Glioblastoma Therapy.

For aggressive brain glioblastoma, the therapy is significantly impaired by blood-brain barrier (BBB) and blood-tumor barrier (BTB). Choosing more than one target from the pool of tumor-stroma interactions is profoundly beneficial to therapeutic approaches. Thus, a multifunctional liposomal system based on anchoring two receptor-specific and penetrable peptides was designed for the combination delivery of BBB-impermeable siRNA and chemotherapeutic docetaxel to brain glioblastoma. Both macroscopic and microscopic specific distributions and targeting effect of the liposomes in the intracranial glioblastoma were confirmed. Superiority in therapeutic efficacies of the siRNA and DTX combination delivery system was revealed from encouraged VEGF gene silencing, tumor cell apoptosis, prolonged survival time, subdued glioblastoma cells in intracranial glioblastoma, and negligible system toxicities after systemic application. Furthermore, the liposomes made better modulation of glioblastoma microenvironment such as the down-regulation of CD31-positive tumor vessels and HIF-1α expression. The transport mechanism of the liposomes delivering the cargos across BBB via receptor-mediated transcytosis without destroying the integrity of BBB has been evaluated from in vitro and in vivo. Therefore, the dual peptides-modified liposomal system provides a safe and noninvasive approach for the delivery of siRNA and chemotherapeutic molecules across the BBB and BTB to target therapy of brain glioblastoma.

Identification and genetic characterization of a novel circular single-stranded DNA virus in a human upper respiratory tract sample.

Metagenomic analysis through high-throughput sequencing is a tool for detecting both known and novel viruses. Using this technique, a novel circular single-stranded DNA (ssDNA) virus genome was discovered in respiratory secretions from a febrile traveler. The virus, named human respiratory-associated PSCV-5-like virus (HRAPLV), has a genome comprising 3,018 bases, with two major putative ORFs inversely encoding capsid (Cap) and replicase (Rep) protein and separated by two intergenic regions. One stem-loop structure was predicted in the larger intergenic region (LIR). The predicted amino acid sequences of the Cap and Rep proteins of HRAPLV showed highest identity to those of porcine stool-associated circular virus 5 isolate CP3 (PoSCV 5) (53.0% and 48.9%, respectively). The host tropism of the virus is unknown, and further study is warranted to determine whether this novel virus is associated with human disease.

Design, synthesis, and biological activity of second-generation synthetic oleanane triterpenoids.

We report the synthesis and biological activity of C-24 demethyl CDDO-Me 2 and the C-28 amide derivatives 3 and 4, which are analogues of the anti-inflammatory synthetic triterpenoid bardoxolone methyl (CDDO-Me) 1. Demethylation of the C-24 methyl group was accomplished via "abnormal Beckmann" rearrangement and subsequent ring A reformation. Amides 3 and 4 were found to be potent inhibitors of the production of the inflammatory mediator NO in vitro.

Significantly elevated number of human infections with H7N9 virus in Jiangsu in eastern China, October 2016 to January 2017.

Since first identified in 2013, the H7N9 virus has caused several waves of human infections in China, with a current wave including a number of patients with very severe disease. Jiangsu is one of the most impacted provinces, whereby as of 31 January 2017, the number of human infections (n = 109) in the ongoing fifth H7N9 wave has exceeded the sum of those in the four preceding ones. Ten of 13 cities in Jiangsu have been affected, and clustered infections as well as one co-infection with seasonal influenza have been observed. With a median age of 58 years and 74.3% (81/109) of patients being male, the characteristics of cases are similar to those in previous waves, however patients with H7N9 seem to have an accelerated disease progression. Preliminary case fatality remains above 30%. No significant viral mutations have been found in key functional loci. Environmental H7N9 detection rate and number of days with high risk ambient temperatures were both significantly elevated during the month of December 2016 when most human infections were reported. A number of municipal governments in Jiangsu have implemented live poultry market closures to impede viral transmission to humans. A detectable decline in human infections has been observed in these municipalities and the entire province since January 2017.