In Science Journals.

Highlights from the family of journals.

Circulating ACE2-expressing extracellular vesicles block broad strains of SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of the coronavirus induced disease 2019 (COVID-19) with evolving variants of concern. It remains urgent to identify novel approaches against broad strains of SARS-CoV-2, which infect host cells via the entry receptor angiotensin-converting enzyme 2 (ACE2). Herein, we report an increase in circulating extracellular vesicles (EVs) that express ACE2 (evACE2) in plasma of COVID-19 patients, which levels are associated with severe pathogenesis.

Generation of potent cellular and humoral immunity against SARS-CoV-2 antigens via conjugation to a polymeric glyco-adjuvant.

The SARS-CoV-2 virus has caused an unprecedented global crisis, and curtailing its spread requires an effective vaccine which elicits a diverse and robust immune response. We have previously shown that vaccines made of a polymeric glyco-adjuvant conjugated to an antigen were effective in triggering such a response in other disease models and hypothesized that the technology could be adapted to create an effective vaccine against SARS-CoV-2. The core of the vaccine platform is the copolymer p(Man-TLR7), composed of monomers with pendant mannose or a toll-like receptor 7 (TLR7) agonist.

Polymersomes Decorated with the SARS-CoV-2 Spike Protein Receptor-Binding Domain Elicit Robust Humoral and Cellular Immunity.

The COVID-19 pandemic underscores the need for rapid, safe, and effective vaccines. In contrast to some traditional vaccines, nanoparticle-based subunit vaccines are particularly efficient in trafficking antigens to lymph nodes, where they induce potent immune cell activation. Here, we developed a strategy to decorate the surface of oxidation-sensitive polymersomes with multiple copies of the SARS-CoV-2 spike protein receptor-binding domain (RBD) to mimic the physical form of a virus particle.

Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2.

There is an urgent need for antiviral agents that treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We screened a library of 1900 clinically safe drugs against OC43, a human beta coronavirus that causes the common cold, and evaluated the top hits against SARS-CoV-2. Twenty drugs significantly inhibited replication of both viruses in cultured human cells.

Polymersomes decorated with SARS-CoV-2 spike protein receptor binding domain elicit robust humoral and cellular immunity.

A diverse portfolio of SARS-CoV-2 vaccine candidates is needed to combat the evolving COVID-19 pandemic. Here, we developed a subunit nanovaccine by conjugating SARS-CoV-2 Spike protein receptor binding domain (RBD) to the surface of oxidation-sensitive polymersomes. We evaluated the humoral and cellular responses of mice immunized with these surface-decorated polymersomes (RBD) compared to RBD-encapsulated polymersomes (RBD) and unformulated RBD (RBD), using monophosphoryl lipid A-encapsulated polymersomes (MPLA PS) as an adjuvant.

Triggering an unexpected earthquake in an uncoupled subduction zone.

In the 1970s, the Shumagin Islands region of the Alaska subduction zone was identified as a seismic gap expected to host a future great [moment magnitude ( ) ≥8.0] earthquake. More recent geodetic data indicate that this region is weakly coupled, and the geologic record shows little evidence of past large events.

Pancreatic Cancer-Associated Diabetes is Clinically Distinguishable From Conventional Diabetes.

Background: Type 3c diabetes mellitus (T3cDM) is diabetes secondary to other pancreatic diseases such as chronic pancreatitis, pancreatic resection, cystic fibrosis, and pancreatic ductal adenocarcinoma (PDA). Clinically, it may easily be confused with conventional type 2 diabetes mellitus (T2DM). A delay in pancreatic cancer diagnosis and treatment leads to a worse outcome.

Drug repurposing screen identifies masitinib as a 3CLpro inhibitor that blocks replication of SARS-CoV-2 .

There is an urgent need for anti-viral agents that treat SARS-CoV-2 infection. The shortest path to clinical use is repurposing of drugs that have an established safety profile in humans. Here, we first screened a library of 1,900 clinically safe drugs for inhibiting replication of OC43, a human beta-coronavirus that causes the common-cold and is a relative of SARS-CoV-2, and identified 108 effective drugs.

CD300LF Polymorphisms of Inbred Mouse Strains Confer Resistance to Murine Norovirus Infection in a Cell Type-Dependent Manner.

Human norovirus is the leading cause of gastroenteritis worldwide, yet basic questions about its life cycle remain unanswered due to an historical lack of robust experimental systems. Recent studies on the closely related murine norovirus (MNV) have identified CD300LF as an indispensable entry factor for MNV. We compared the MNV susceptibilities of cells from different mouse strains and identified polymorphisms in murine CD300LF which are critical for its function as an MNV receptor.

Suppression of Cytotoxic T Cell Functions and Decreased Levels of Tissue-Resident Memory T Cells during H5N1 Infection.

Seasonal influenza virus infections cause mild illness in healthy adults, as timely viral clearance is mediated by the functions of cytotoxic T cells. However, avian H5N1 influenza virus infections can result in prolonged and fatal illness across all age groups, which has been attributed to the overt and uncontrolled activation of host immune responses. Here, we investigate how excessive innate immune responses to H5N1 impair subsequent adaptive T cell responses in the lungs.

Optimization of 4-Aminopiperidines as Inhibitors of Influenza A Viral Entry That Are Synergistic with Oseltamivir.

Vaccination is the most prevalent prophylactic means for controlling seasonal influenza infections. However, an effective vaccine usually takes at least 6 months to develop for the circulating strains. Therefore, new therapeutic options are needed for the acute treatment of influenza infections to control this virus and prevent epidemics/pandemics from developing.

Autophagy and Noroviruses.

Autophagy is an essential cellular process by which a cell degrades materials within its cytoplasm. Intracellular pathogens like viruses must deal with autophagy, either positively or negatively, for their own survival and replication. For some viruses, autophagy can even play proviral roles, helping their replication or dissemination.

EIF1AX Mutation in a Patient with Hürthle Cell Carcinoma.

The EIF1AX gene is a novel cancer gene that has been reported in the tumorigenesis of papillary thyroid carcinoma, follicular variant papillary thyroid carcinoma, and anaplastic thyroid carcinoma. A 71-year-old woman presented with a right thyroid mass, which was follicular neoplasm on cytology. The fine needle aspirate of the nodule was examined by next-generation sequencing and found to harbor EIF1AX and TP53 mutations.

Management of hyperglycemia in the neurosurgery patient.

Hyperglycemia is associated with adverse outcomes in patients who are candidates for or underwent neurosurgical procedures. Specific concerns and settings that relate to these patients are preoperative glycemic control, intraoperative control, management in the neurological intensive care unit (NICU), and postoperative control. In each of these settings, physicians have to ensure appropriate glycemic control to prevent or minimize adverse events.

Continuing megathrust earthquake potential in Chile after the 2014 Iquique earthquake.

The seismic gap theory identifies regions of elevated hazard based on a lack of recent seismicity in comparison with other portions of a fault. It has successfully explained past earthquakes (see, for example, ref. 2) and is useful for qualitatively describing where large earthquakes might occur.

Subclinical hyperthyroidism: current concepts and scintigraphic imaging.

Subclinical hyperthyroidism is defined as normal serum free thyroxine and a free triiodothyronine level, with a thyroid-stimulating hormone level suppressed below the normal range and is usually undetectable. Although patients with this diagnosis have no or few signs and symptoms of overt thyrotoxicosis, there is sufficient evidence that it is associated with a relatively higher risk of supraventricular arrhythmias as well as the acceleration or the development of osteoporosis. Consequently, the approach to the patient with subclinical hyperthyroidism is controversial, that is, therapeutic intervention versus watchful waiting.

A great earthquake rupture across a rapidly evolving three-plate boundary.

On 1 April 2007 a great, tsunamigenic earthquake (moment magnitude 8.1) ruptured the Solomon Islands subduction zone at the triple junction where the Australia and Solomon Sea-Woodlark Basin plates simultaneously underthrust the Pacific plate with different slip directions. The associated abrupt change in slip direction during the great earthquake drove convergent anelastic deformation of the upper Pacific plate, which generated localized uplift in the forearc above the subducting Simbo fault, potentially amplifying local tsunami amplitude.

Dual PPAR alpha/gamma agonists: promises and pitfalls in type 2 diabetes.

Type 2 diabetes mellitus is a disease of complex pathogenesis and pleiotropic clinical manifestations. The greatest clinical challenge in this disease is the prevention of the long-term complications, many of which involve cardiovascular outcomes. The peroxisome proliferator-activated receptor (PPAR) alpha and gamma isoforms of the family of nuclear transcription factors are pharmaceutical targets for therapeutic intervention because they can potentially ameliorate not only the hyperglycemia of diabetes, but also the dyslipidemia that is characteristic of this disorder (low high-density lipoprotein cholesterol, high triglycerides, small, dense low-density lipoprotein particles).