The microbiome's influence on obesity: mechanisms and therapeutic potential.

In 2023, the World Obesity Atlas Federation concluded that more than 50% of the world's population would be overweight or obese within the next 12 years. At the heart of this epidemic lies the gut microbiota, a complex ecosystem that profoundly influences obesity-related metabolic health. Its multifaced role encompasses energy harvesting, inflammation, satiety signaling, gut barrier function, gut-brain communication, and adipose tissue homeostasis.

Human transferrin receptor can mediate SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been detected in almost all organs of coronavirus disease-19 patients, although some organs do not express angiotensin-converting enzyme-2 (ACE2), a known receptor of SARS-CoV-2, implying the presence of alternative receptors and/or co-receptors. Here, we show that the ubiquitously distributed human transferrin receptor (TfR), which binds to diferric transferrin to traffic between membrane and endosome for the iron delivery cycle, can ACE2-independently mediate SARS-CoV-2 infection. Human, not mouse TfR, interacts with Spike protein with a high affinity (K ~2.

EPidemiology, clinical characteristics and Outcomes of 4546 adult admissions to high-dependency and intensive care units in Kenya (EPOK): a multicentre registry-based observational study.

Objective: to describe clinical, management and outcome features of critically ill patients admitted to intensive care units (ICUs) and high dependency units (HDUs) in Kenya.

Design: prospective registry-based observational study.

Setting: three HDUs and eight ICUs in Kenya.

Costs of seasonal influenza vaccine delivery in a pediatric demonstration project for children aged 6-23 months - Nakuru and Mombasa Counties, Kenya, 2019-2021.

Background: During November 2019-October 2021, a pediatric influenza vaccination demonstration project was conducted in four sub-counties in Kenya. The demonstration piloted two different delivery strategies: year-round vaccination and a four-month vaccination campaign. Our objective was to compare the costs of both delivery strategies.

Orientational Nanoconjugation with Gold Endows Marked Antimicrobial Potential and Drugability of Ultrashort Dipeptides.

Antibiotic resistance is a global threat. Antimicrobial peptides (AMPs) are highly desirable to treat multidrug-resistant pathogen infection. However, few AMPs are clinically available, due to high cost, instability, and poor selectivity.

Resilience of routine childhood immunization services in two counties in Kenya in the face of the COVID-19 pandemic.

The recently emerged coronavirus disease 2019 (COVID-19) has caused considerable morbidity and mortality worldwide and disrupted health services. We describe the effect of the COVID-19 pandemic on utilization of childhood vaccination services during the pandemic. Using a mixed methods approach combining retrospective data review, a cross-sectional survey, focus group discussions among care givers and key informant interviews among nurses, we collected data between May and September 2021 in Mombasa and Nakuru counties.

Wikstroemia indica (L.) C. A. Mey. Exerts analgesic activity by inhibiting Na1.7 channel.

Ethnopharmacological Relevance: Wikstroemia indica (L.) C. A.

Design methods for antimicrobial peptides with improved performance.

The recalcitrance of pathogens to traditional antibiotics has made treating and eradicating bacterial infections more difficult. In this regard, developing new antimicrobial agents to combat antibiotic-resistant strains has become a top priority. Antimicrobial peptides (AMPs), a ubiquitous class of naturally occurring compounds with broad-spectrum antipathogenic activity, hold significant promise as an effective solution to the current antimicrobial resistance (AMR) crisis.

The role of TRPA1 channels in thermosensation.

Transient receptor potential ankyrin 1 (TRPA1) is a polymodal nonselective cation channel sensitive to different physical and chemical stimuli. TRPA1 is associated with many important physiological functions in different species and thus is involved in different degrees of evolution. TRPA1 acts as a polymodal receptor for the perceiving of irritating chemicals, cold, heat, and mechanical sensations in various animal species.

Lipopolysaccharide-binding protein expression is increased by stress and inhibits monoamine synthesis to promote depressive symptoms.

Monoamine insufficiency is suggested to be associated with depressive features such as sadness, anhedonia, insomnia, and cognitive dysfunction, but the mechanisms that cause it are unclear. We found that the acute-phase protein lipopolysaccharide-binding protein (LBP) inhibits monoamine biosynthesis by acting as an endogenous inhibitor of dopamine-β-hydroxylase (DBH) and aromatic-L-amino-acid-decarboxylase (DDC). LBP expression was increased in individuals with depression and by diverse stress challenges in mice.

Vertebrate OTOP1 is also an alkali-activated channel.

Although alkaline sensation is critical for survival, alkali-activated receptors are yet to be identified in vertebrates. Here, we showed that the OTOP1 channel can be directly activated by extracellular alkali. Notably, OTOP1 biphasically mediated proton influx and efflux with extracellular acid and base stimulation, respectively.

Human antimicrobial peptide LL-37 contributes to Alzheimer's disease progression.

As a prime mover in Alzheimer's disease (AD), microglial activation requires membrane translocation, integration, and activation of the metamorphic protein chloride intracellular channel 1 (CLIC1), which is primarily cytoplasmic under physiological conditions. However, the formation and activation mechanisms of functional CLIC1 are unknown. Here, we found that the human antimicrobial peptide (AMP) LL-37 promoted CLIC1 membrane translocation and integration.

Genetic diversity and population structure of wild and cultivated Crotalaria species based on genotyping-by-sequencing.

Crotalaria is a plant genus that is found all over the world, with over 700 species of herbs and shrubs. The species are potential alternative food and industrial crops due to their adaptability to different environments. Currently, information on the genetic diversity and population structure of these species is scanty.

Hypoxia and low temperature upregulate transferrin to induce hypercoagulability at high altitude.

Studies have shown significantly increased thromboembolic events at high altitude. We recently reported that transferrin could potentiate blood coagulation, but the underlying mechanism for high altitude-related thromboembolism is still poorly understood. Here, we examined the activity and concentration of plasma coagulation factors and transferrin in plasma collected from long-term human residents and short-stay mice exposed to varying altitudes.

Bioactive Peptides and Proteins from Centipede Venoms.

Venoms are a complex cocktail of biologically active molecules, including peptides, proteins, polyamide, and enzymes widely produced by venomous organisms. Through long-term evolution, venomous animals have evolved highly specific and diversified peptides and proteins targeting key physiological elements, including the nervous, blood, and muscular systems. Centipedes are typical venomous arthropods that rely on their toxins primarily for predation and defense.

Venom resistance mechanisms in centipede show tissue specificity.

Venomous animals utilize venom glands to secrete and store powerful toxins for intraspecific and/or interspecific antagonistic interactions, implying that tissue-specific resistance is essential for venom glands to anatomically separate toxins from other tissues. Here, we show the mechanism of tissue-specific resistance in centipedes (Scolopendra subspinipes mutilans), where the splice variant of the receptor repels its own toxin. Unlike the well-known resistance mechanism by mutation in a given exon, we found that the KCNQ1 channel is highly expressed in the venom gland as a unique splice variant in which the pore domain and transmembrane domain six, partially encoded by exon 6 (rather than 7 as found in other tissues), contain eleven mutated residues.

Centipede Venom: A Potential Source of Ion Channel Modulators.

Centipedes are one of the most ancient and successful living venomous animals. They have evolved spooky venoms to deter predators or hunt prey, and are widely distributed throughout the world besides Antarctica. Neurotoxins are the most important virulence factor affecting the function of the nervous system.

Potent Ca3.2 channel inhibitors exert analgesic effects in acute and chronic pain models.

Pain is the most common presenting physical symptom and a primary reason for seeking medical care, which chronically affects people's mental health and social life. Ca3.2 channel plays an essential role in the peripheral processing maintenance of pain states.

Anticarin- shows a promising anti-osteosarcoma effect by specifically inhibiting CCT4 to impair proteostasis.

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome.

Bioactive Peptides and Proteins from Wasp Venoms.

Wasps, members of the order Hymenoptera, use their venom for predation and defense. Accordingly, their venoms contain various constituents acting on the circulatory, immune and nervous systems. Wasp venom possesses many allergens, enzymes, bioactive peptides, amino acids, biogenic amines, and volatile matters.

An inhibitor of leukotriene-A hydrolase from bat salivary glands facilitates virus infection.

SignificanceAn immunosuppressant protein (MTX), which facilitates virus infection by inhibiting leukotriene A hydrolase (LTAH) to produce the lipid chemoattractant leukotriene B (LTB), was identified and characterized from the submandibular salivary glands of the bat . To the best of our knowledge, this is a report of an endogenous LTAH inhibitor in animals. MTX was highly concentrated in the bat salivary glands, suggesting a mechanism for the generation of immunological privilege and immune tolerance and providing evidence of viral shedding through oral secretions.

Shrew's venom quickly causes circulation disorder, analgesia and hypokinesia.

Multiple representatives of eulipotyphlan mammals such as shrews have oral venom systems. Venom facilitates shrews to hunt and/or hoard preys. However, little is known about their venom composition, and especially the mechanism to hoard prey in comatose states for meeting their extremely high metabolic rates.

Peptide OPTX-1 From Tick Inhibits the pS273R Protease of African Swine Fever Virus.

African swine fever virus (ASFV) is a large double-stranded DNA virus and causes high mortality in swine. ASFV can be transmitted by biological vectors, including soft ticks in genus but not hard ticks. However, the underlying mechanisms evolved in the vectorial capacity of soft ticks are not well-understood.

Toward an understanding of tree frog (Hyla japonica) for predator deterrence.

Gene-encoded peptides with distinct potent bioactivities enable several animals to take advantage of fierce interspecific interaction, as seen in the skin secretion of amphibians. Unlike, most amphibian species that frequently switches terrestrial-aquatic habitats and hides easily from terrestrial predators, tree frogs of small body size are considered as the vulnerable prey in the arboreal habitat. Here, we show the structural and functional diversity of peptide families based on the skin transcriptome of Hyla japonica, which has evolved to be wrapped as an efficient chemical toolkit for defensive use in arboreal habitat.