Distributions of Lanostene-Derived Triterpenoids and Glucan Content in the Fruiting Bodies of the Australian Species.

Lanostene-derived triterpenoids and β-glucans are important metabolites in mushrooms associated with benefits to human health. The medicinal value of the Australian species remains unclear, with no data on triterpenoid distribution or glucan content. In the present study, 22 Australian specimens were analyzed for triterpenoid and glucan contents.

EEG and fNIRS are associated with situation awareness (hazard) prediction during a driving task.

Situation awareness (SA) is important in many demanding tasks (e.g. driving).

Vertical connectivity of microbiome and metabolome reveals depth-dependent variations across a deep cold-seep water column.

Deciphering the vertical connectivity of oceanic microbiome and metabolome is crucial for understanding the carbon sequestration and achieving the carbon neutrality. However, we lack a systematic view of the interplay among particle transport, microbial community, and metabolic trait across depths. Through integrating the biogeochemical, microbial, and metabolic characteristics of a deep cold-seep water column (∼1989 m), we find the altered connectivity of microbial community and dissolved organic matter (DOM) across depths.

Uptake and Use of Care Companion, a Web-Based Information Resource for Supporting Informal Carers of Older People: Mixed Methods Study.

Background: Informal carers play a major role in supporting relatives and friends who are sick, disabled, or frail. Access to information, guidance, and support that are relevant to the lives and circumstances of carers is critical to carers feeling supported in their role. When unmet, this need is known to adversely affect carer resilience and well-being.

Improving the Therapeutic Index of Smp24, a Venom-Derived Antimicrobial Peptide: Increased Activity against Gram-Negative Bacteria.

Antimicrobial peptides (AMPs) are naturally occurring compounds which possess a rapid killing mechanism and low resistance potential. Consequently, they are being viewed as potential alternatives to traditional antibiotics. One of the major factors limiting further development of AMPs is off-target toxicity.

Filamentous fungi for future functional food and feed.

In this review, we offer our opinion of current and expected trends regarding the use of mushrooms and mycelia in food and feed. Mushrooms have provided food for millennia and production methods and species diversity have recently expanded. Beyond mushrooms, cultured fungal mycelia are now harvested as a primary product for food.

Scorpion Venom Antimicrobial Peptides Induce Caspase-1 Dependant Pyroptotic Cell Death.

Within the last decade, several peptides have been identified according to their ability to inhibit the growth of microbial pathogens. These antimicrobial peptides (AMPs) are a part of the innate immune system of all living organisms. Many studies on their effects on prokaryotic microorganisms have been reported; some of these peptides have cytotoxic properties although the molecular mechanisms underlying their activity on eukaryotic cells remain poorly understood.

In vitro and in vivo drug screens of tumor cells identify novel therapies for high-risk child cancer.

Biomarkers which better match anticancer drugs with cancer driver genes hold the promise of improved clinical responses and cure rates. We developed a precision medicine platform of rapid high-throughput drug screening (HTS) and patient-derived xenografting (PDX) of primary tumor tissue, and evaluated its potential for treatment identification among 56 consecutively enrolled high-risk pediatric cancer patients, compared with conventional molecular genomics and transcriptomics. Drug hits were seen in the majority of HTS and PDX screens, which identified therapeutic options for 10 patients for whom no targetable molecular lesions could be found.

Disentangling the Effects of Physicochemical, Genetic, and Microbial Properties on Phase-Driven Resistome Dynamics during Multiple Manure Composting Processes.

Composting alters manure-derived antibiotic resistance genes (ARGs) to a certain extent, which is largely dependent upon the composting phase, manure type, microbial phylogeny, and physicochemical properties. However, little is known about how these determinants influence the fate and dynamics of ARGs as well as the mechanisms underlying the ecological process of ARGs during composting. Here, we investigated the temporal patterns of ARGs and their correlations with a series of physicochemical, genetic, and microbial properties during pilot-scale composting of chicken, maggot, bovine, and swine manure.

Scorpion Venom Antimicrobial Peptides Induce Siderophore Biosynthesis and Oxidative Stress Responses in Escherichia coli.

The increasing development of microbial resistance to classical antimicrobial agents has led to the search for novel antimicrobials. Antimicrobial peptides (AMPs) derived from scorpion and snake venoms offer an attractive source for the development of novel therapeutics. Smp24 (24 amino acids [aa]) and Smp43 (43 aa) are broad-spectrum AMPs that have been identified from the venom gland of the Egyptian scorpion and subsequently characterized.

Prevalence of antibiotic resistance genes and bacterial pathogens along the soil-mangrove root continuum.

Plants roots are colonised by soil bacteria that are known to be the reservoir of antibiotic resistance genes (ARGs). ARGs can transfer between these microorganisms and pathogens, but to what extent these ARGs and pathogens disseminate from soil into plant is poorly understood. Here, we examined a high-resolution resistome profile along the soil-root continuum of mangrove saplings using amplicon and metagenomic sequencing.

PC945, a Novel Inhaled Antifungal Agent, for the Treatment of Respiratory Fungal Infections.

Disease due to pulmonary infection remains a significant unmet need, particularly in immunocompromised patients, patients in critical care and those with underlying chronic lung diseases. To date, treatment using inhaled antifungal agents has been limited to repurposing available systemic medicines. PC945 is a novel triazole antifungal agent, a potent inhibitor of CYP51, purpose-designed to be administered via inhalation for high local lung concentrations and limited systemic exposure.

Safety and nonclinical and clinical pharmacokinetics of PC945, a novel inhaled triazole antifungal agent.

PC945 is a novel antifungal triazole formulated for nebulized delivery to treat lung Aspergillus infections. Pharmacokinetic and safety profiles from nonclinical studies and clinical trials in healthy subjects, and subjects with mild asthma were characterized. Toxicokinetics were assessed following daily 2-hour inhalation for 14 days.

Safety and Antiviral Effects of Nebulized PC786 in a Respiratory Syncytial Virus Challenge Study.

Background: PC786 is a nebulized nonnucleoside respiratory syncytial virus (RSV) polymerase inhibitor designed to treat RSV, which replicates in the superficial layer of epithelial cells lining the airways.

Methods: Fifty-six healthy volunteers inoculated with RSV-A (Memphis 37b) were randomly dosed with either nebulized PC786 (5 mg) or placebo, twice daily for 5 days, from either 12 hours after confirmation of RSV infection or 6 days after virus inoculation. Viral load (VL), disease severity, pharmacokinetics, and safety were assessed until discharge.

Comparison of polysaccharide glycoconjugates as candidate vaccines to combat Clostridiodes (Clostridium) difficile.

Two known Clostridiodes (Clostridium) difficile surface antigens, a lipoteichoic acid (LTA) and a polysaccharide (PS-II) were isolated and purified in order to prepare glycoconjugate vaccines to the carrier protein human serum albumin utilising a reductive amination strategy. Mice and rabbits were immunized with a prime and two boost strategy and the resulting sera were examined for their ability to recognise the purified homologous antigens and subsequently killed whole cells of C. difficile strains and other Clostridia species.

Rapid Deployment of Inpatient Telemedicine In Response to COVID-19 Across Three Health Systems.

Objective: To reduce pathogen exposure, conserve personal protective equipment, and facilitate health care personnel work participation in the setting of the COVID-19 pandemic, three affiliated institutions rapidly and independently deployed inpatient telemedicine programs during March 2020. We describe key features and early learnings of these programs in the hospital setting.

Methods: Relevant clinical and operational leadership from an academic medical center, pediatric teaching hospital, and safety net county health system met to share learnings shortly after deploying inpatient telemedicine.

Structural Elements of the Biomechanical System of Soft Tissue.

In living organisms, forces are constantly generated and transmitted throughout tissue. Such forces are generated through interaction with the environment and as a result of the body's endogenous movement. If these internally or externally originating forces exceed the ability of tissues to cope with the applied forces, (i.

In vitro antifungal activity of a novel topical triazole PC945 against emerging yeast Candida auris.

Objectives: Management of Candida auris infection is difficult as this yeast exhibits resistance to different classes of antifungals, necessitating the development of new antifungals. The aim of this study was to investigate the susceptibility of C. auris to a novel antifungal triazole, PC945, optimized for topical delivery.