Notes

A new document regarding odd-scaled reptile (Serpentes, Xenodermidae) coming from Vietnam: expanded outline involving Parafimbrios vietnamensis according to integrative taxonomy.
The COVID-19 pandemic has extracted an enormous physical health toll on many millions worldwide, and the wider societal impact from economic turmoil, unemployment, social isolation and so forth continue to be measured. A less explored aspect has been the psychological impact on treating healthcare staff, with emerging evidence of 'moral injury' and mental illness for some. JNK inhibitor in vivo This review explores the evidence base for implementing a tiered model of care to minimise this and foster 'post-traumatic growth', and describes the authors' implementation of this in the London Nightingale hospital, with lessons for the armed forces.
Nasopharyngeal carcinoma (NPC) is primarily caused by the Epstein-Barr virus (EBV) infection in NPC endemic areas. EBNA1 is an EBV-encoded nuclear antigen, which plays a critical role in the maintenance and replication of EBV genome. However, the mechanisms of EBNA1-promoted NPC immune escape are unknown. Regulatory T (Treg) cells are among the key regulators in restraining antitumor responses. However, the mechanisms of accumulation of Treg cells in NPC have not been defined. This study attempted to identify the detailed mechanisms of EBNA1 functions as a tumor accelerator to promote NPC immune escape by enhancing chemoattraction of Treg cells.

mRNA profiles were determined by next-generation sequencing in NPC cells. In vitro and in vivo assays were performed to analyze the role of EBNA1 in regulation of recruitment of Treg cells. Colocation and coimmunoprecipitation analyzes were used to identify the SMAD3/c-JUN complex. Chromatin immunoprecipitation assay and dual luciferase reporter assays were designted by c-JUN, which directly binds to the miR-200a promoter and forms a c-JUN-miR-200a-CXCL12-c-JUN feedback loop. In addition, enhanced CXCL12 efficiently attracts CXCR4-positive Treg cells to remodel an immunosuppressive microenvironment.

EBV-EBNA1 promotes chemotactic migration of Treg cells via the TGFβ1-SMAD3-PI3K-AKT-c-JUN-miR-200a-CXCL12-CXCR4 axis in the NPC microenvironment. These results suggest that EBV-EBNA1 may serve as a potential therapeutic target to reshape the NPC microenvironment.
EBV-EBNA1 promotes chemotactic migration of Treg cells via the TGFβ1-SMAD3-PI3K-AKT-c-JUN-miR-200a-CXCL12-CXCR4 axis in the NPC microenvironment. These results suggest that EBV-EBNA1 may serve as a potential therapeutic target to reshape the NPC microenvironment.
Targeted and effective treatment options are needed for solid tumors, including glioblastoma (GBM), where survival rates with standard treatments are typically less than 2 years from diagnosis. Solid tumors pose many barriers to immunotherapies, including therapy half-life and persistence, tumor penetrance, and targeting. Therapeutics delivered systemically may not traffic to the tumor site. If cellular therapies or drugs are able to access the tumor site, or can be delivered directly within the tumor, treatments may not persist for the duration necessary to reduce or eliminate tumor burden. An approach that allows durable and titratable local therapeutic protein delivery could improve antitumor efficacy while minimizing toxicities or unwanted on-target, off-tissue effects.

In this study, human monocyte-derived macrophages were genetically engineered to secrete a bispecific T cell engager (BiTE) specific to the mutated epidermal growth factor variant III (EGFRvIII) expressed by some GBM tumors. We investiiltrate and persist in solid tumor tissue could overcome many of the obstacles associated with systemic delivery of immunotherapies. We have found that human GEMs can locally and constitutively express one or more therapeutic proteins, which may help recruit T cells and transform the immunosuppressive tumor microenvironment to better support antitumor immunity.
The ability of macrophages to infiltrate and persist in solid tumor tissue could overcome many of the obstacles associated with systemic delivery of immunotherapies. We have found that human GEMs can locally and constitutively express one or more therapeutic proteins, which may help recruit T cells and transform the immunosuppressive tumor microenvironment to better support antitumor immunity.
We report
patterns of neuroinflammation and abnormal protein aggregation in seven cases of familial frontotemporal dementia (FTD) with mutations in MAPT, GRN and C9orf72 genes.

Using positron emission tomography (PET), we explored the association of the distribution of activated microglia, as measured by the radioligand [
C]PK11195, and the regional distribution of tau or TDP-43 pathology, indexed using the radioligand [
F]AV-1451. The familial FTD PET data were compared with healthy controls.

Patients with familial FTD across all mutation groups showed increased [
C]PK11195 binding predominantly in frontotemporal regions, with additional regions showing abnormalities in individuals. Patients with MAPT mutations had a consistent distribution of [
F]AV-1451 binding across the brain, with heterogeneous distributions among carriers of GRN and C9orf72 mutations.

This case series suggests that neuroinflammation is part of the pathophysiology of familial FTD, warranting further consideration of immunomodulatory therapies for disease modification and prevention.
This case series suggests that neuroinflammation is part of the pathophysiology of familial FTD, warranting further consideration of immunomodulatory therapies for disease modification and prevention.Medium-chain fatty acids (MCFAs) have in rodents been shown to have protective effects on glucose homeostasis during high-fat overfeeding. In this study, we investigated whether dietary MCFAs protect against insulin resistance induced by a hypercaloric high-fat diet in humans. Healthy, lean men ingested a eucaloric control diet and a 3-day hypercaloric high-fat diet (increase of 75% in energy, 81-83% energy [E%] from fat) in randomized order. For one group (n = 8), the high-fat diet was enriched with saturated long-chain FAs (LCSFA-HFD), while the other group (n = 9) ingested a matched diet, but with ∼30 g (5E%) saturated MCFAs (MCSFA-HFD) in substitution for a corresponding fraction of the saturated long-chain fatty acids (LCFAs). A hyperinsulinemic-euglycemic clamp with femoral arteriovenous balance and glucose tracer was applied after the control and hypercaloric diets. In LCSFA-HFD, whole-body insulin sensitivity and peripheral insulin-stimulated glucose disposal were reduced. These impairments were prevented in MCSFA-HFD, accompanied by increased basal fatty acid oxidation, maintained glucose metabolic flexibility, increased nonoxidative glucose disposal related to lower starting glycogen content, and increased glycogen synthase activity, together with increased muscle lactate production.
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