Aquatic birds harbor diverse influenza A viruses and are a major viral reservoir in nature. The recent discovery of influenza viruses of a new H17N10 subtype in Central American fruit bats suggests that other New World species may similarly carry divergent influenza viruses. Using consensus degenerate RT-PCR, we identified a novel influenza A virus, designated as H18N11, in a flat-faced fruit bat (Artibeus planirostris) from Peru. Serologic studies with the recombinant H18 protein indicated that several Peruvian bat species were infected by this virus. Phylogenetic analyses demonstrate that, in some gene segments, New World bats harbor more influenza virus genetic diversity than all other mammalian and avian species combined, indicative of a long-standing host-virus association. Structural and functional analyses of the hemagglutinin and neuraminidase indicate that sialic acid is not a ligand for virus attachment nor a substrate for release, suggesting a unique mode of influenza A virus attachment and activation of membrane fusion for entry into host cells. Taken together, these findings indicate that bats constitute a potentially important and likely ancient reservoir for a diverse pool of influenza viruses.

A new red-emissive bioprobe TPE-red-2AP2H was developed by taking advantage of the unique emission feature of tetraphenylethylene and a cancer cell-specific peptide. By responding to the target protein and the acidic microenvironment of tumor cells, activated fluorescence bioimaging was achieved with high signal-to-noise ratio and without involving mutiple washing steps. Apart from targeting the membrane-anchored LAPTM4B proteins, TPE-red-2AP2H was successfully utilized to trace the intracellular movement of LAPTM4B protein. The generation of (1)O2 under visible light irradiation makes this bioprobe also promising for targeted-photodynamic therapy. By discriminating the expression level of the target protein, TPE-red-2AP2H can respond to the progression status of tumors with different photodynamic therapy effect.

Coronavirus disease 2019 (COVID-19) is a novel and lethal infectious disease, posing a threat to global health security. The number of cases has increased rapidly, but no data concerning kidney transplant (KTx) recipients infected with COVID-19 are available. To present the epidemiological, clinical, and therapeutic characteristics of KTx recipients infected with COVID-19, we report on a case series of five patients who were confirmed as having COVID-19 through nucleic acid testing (NAT) from January 1, 2020 to February 28, 2020. The most common symptoms on admission to hospital were fever (five patients, 100%), cough (five patients, 100%), myalgia or fatigue (three patients, 60%), and sputum production (three patients, 60%); serum creatinine or urea nitrogen levels were slightly higher than those before symptom onset. Four patients received a reduced dose of maintenance immunosuppressive therapy during hospitalization. As of March 4, 2020 NAT was negative for COVID-19 in three patients twice in succession, and their computed tomography scans showed improved images. Although greater patient numbers and long-term follow-up data are needed, our series demonstrates that mild COVID-19 infection in KTx recipients can be managed using symptomatic support therapy combined with adjusted maintenance immunosuppressive therapy.

The 3D-structure of the major surface viral antigen from the recent H1N1 pandemic influenza virus (A/Darwin/2001/2009) was determined to 2.8 Å resolution. The structure was used to analyze changes in the HA that have emerged during the first 11 months of the pandemic and have raised public health concerns. Receptor binding properties of this protein reveals a strict preference for human-type receptors.

eral mechanisms can underlie short-term synaptic depression, including vesicle depletion, receptor desensitization, and changes in presynaptic release probability. To determine which mechanisms affect depression under physiological conditions, we studied the synapse formed by auditory nerve fibers onto bushy cells in the anteroventral cochlear nucleus (the "endbulb of Held") using voltage-clamp recordings of brain slices from P15-P21 mice near physiological temperatures. Depression of both ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) excitatory postsynaptic currents (EPSCs) showed two phases of recovery. The fast component of depression for the AMPA EPSC was eliminated by cyclothiazide and aniracetam, suggesting it results from desensitization. The fast component of depression for the NMDA EPSC was reduced by the low-affinity antagonist L-AP5, suggesting it results from saturation. The remaining depression in AMPA and NMDA components is identical and therefore presynaptic in origin. It is likely to result from presynaptic vesicle depletion. Recovery from depression after trains of activity was slowed by the application of EGTA-AM, suggesting that the endbulb has a residual-calcium-dependent form of recovery. We developed a model that incorporates depletion, desensitization, and calcium-dependent recovery. This model replicated experimental findings over a range of experimental conditions. The model further indicated that desensitization plays only a minor role during prolonged activity, in large part because presynaptic release is so depleted. Thus depletion appears to be the dominant mechanism of depression at the endbulb during normal activity. Furthermore, calcium-dependent recovery at the endbulb is critical to prevent complete rundown during high activity and to preserve the reliability of information transmission.

COVID-19 has rapidly become a global challenge. 1 We read with interest the article by Bezzio et al 1 that reported the characteristics and outcomes of COVID-19 patients with pre-existing IBD. Patients with pre-existing cirrhosis, who have immune dysfunction and poorer outcomes from acute respiratory distress syndrome (ARDS) than patients without cirrhosis, are also considered a high-risk population for COVID-19. 2 3 In previous studies, the proportion of COVID-19 patients with pre-existing liver conditions ranged from 2% to 11%. 2 However, the clinical course and risk factors for mortality in these patients has not yet been reported. This retrospective multicentre study (COVID-Cirrhosis-CHESS, ClinicalTrials. gov NCT04329559) included consecutive adult patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pre-existing cirrhosis from 16 designated hospitals in China between 31 December 2019 and 24 March 2020. Patient characteristics are summarised in table 1. Twenty-one COVID-19 patients with preexisting cirrhosis (Child-Pugh class A, B and C in 16, 3 and 2 patients, respectively) were included in the analysis. The median age was 68 years; 11 (52.4%) were male. Most patients had compensated cirrhosis (81.0%) and chronic HBV infection was the most common aetiology (57.1%). Comorbidities other than cirrhosis were present in most patients (66.7%). In previous studies, older age, male sex and pre-existing comorbidities were associated with higher risk of mortality for COVID-19. 4 5 Here, there were no significant differences between survivors (n=16) and non-survivors (n=5) in age, sex, comorbidities, aetiology of cirrhosis, stage of cirrhosis, Child-Pugh class, Model for End-stage Liver Disease (MELD) score, interval between onset and admission, or onset symptoms of COVID-19. Comorbidities have been associated with adverse outcomes in cirrhosis, 6 but our analysis did not show clear prognostic associations-possibly due to the small size and narrow composition of the study population.

Effective annual influenza vaccination requires frequent changes in vaccine composition due to both antigenic shift for different subtype hemagglutinins (HAs) and antigenic drift in a particular HA. Here we present a broadly neutralizing human monoclonal antibody with an unusual binding modality. The antibody, designated CT149, was isolated from convalescent patients infected with pandemic H1N1 in 2009. CT149 is found to neutralize all tested group 2 and some group 1 influenza A viruses by inhibiting low pH-induced, HA-mediated membrane fusion. It promotes killing of infected cells by Fc-mediated antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. X-ray crystallographic data reveal that CT149 binds primarily to the fusion domain in HA2, and the light chain is also largely involved in binding. The epitope recognized by this antibody comprises amino-acid residues from two adjacent protomers of HA. This binding characteristic of CT149 will provide more information to support the design of more potent influenza vaccines.

Muscle-invasive bladder cancer (MIBC) is an aggressive disease with limited therapeutic options. Although immunotherapies are approved for MIBC, the majority of patients fail to respond, suggesting existence of complementary immune evasion mechanisms. Here, we report that the PPARγ/RXRα pathway constitutes a tumor-intrinsic mechanism underlying immune evasion in MIBC. Recurrent mutations in RXRα at serine 427 (S427F/Y), through conformational activation of the PPARγ/RXRα heterodimer, and focal amplification/overexpression of PPARγ converge to modulate PPARγ/RXRα-dependent transcription programs. Immune cell-infiltration is controlled by activated PPARγ/RXRα that inhibits expression/secretion of inflammatory cytokines. Clinical data sets and an in vivo tumor model indicate that PPARγHigh/RXRαS427F/Y impairs CD8+ T-cell infiltration and confers partial resistance to immunotherapies. Knockdown of PPARγ or RXRα and pharmacological inhibition of PPARγ significantly increase cytokine expression suggesting therapeutic approaches to reviving immunosurveillance and sensitivity to immunotherapies. Our study reveals a class of tumor cell-intrinsic “immuno-oncogenes” that modulate the immune microenvironment of cancer.