Ubiquitination, a crucial post-translational modification, plays a role in nearly all physiological processes. Its functional execution depends on a series of catalytic reactions involving numerous proteases. TRIM26, a protein belonging to the TRIM family, exhibits E3 ubiquitin ligase activity because of its RING structural domain, and is present in diverse cell lineages. Over the last few decades, TRIM26 has been documented to engage in numerous physiological and pathological processes as a controller, demonstrating a diverse array of biological roles. Despite the growing research interest in TRIM26, there has been limited attention given to examining the protein\'s structure and function in existing reviews. This review begins with a concise overview of the composition and positioning of TRIM26 and then proceeds to examine its roles in immune response, viral invasion, and inflammatory processes. Simultaneously, we demonstrate the contribution of TRIM26 to the progression of various diseases, encompassing numerous malignancies and neurologic conditions. Finally, we have investigated the potential areas for future research on TRIM26.

BACKGROUND: T-type calcium channels, characterized as low-voltage activated (LVA) calcium channels, play crucial physiological roles across a wide range of tissues, including both the neuronal and nonneuronal systems. Using in situ hybridization and RNA interference (RNAi) techniques in vitro, we previously identified the tissue distribution and physiological function of the T-type calcium channel α1 subunit (DdCα1G) in the plant-parasitic nematode Ditylenchus destructor.
RESULTS: To further characterize the functional role of DdCα1G, we employed a combination of immunohistochemistry and fungus-mediated RNAi and found that DdCα1G was clearly distributed in stylet-related tissue, oesophageal gland-related tissue, secretory-excretory duct-related tissue and male spicule-related tissue. Silencing DdCα1G led to impairments in the locomotion, feeding, reproductive ability and protein secretion of nematodes. To confirm the defects in behavior, we used phalloidin staining to examine muscle changes in DdCα1G-RNAi nematodes. Our observations demonstrated that defective behaviors are associated with related muscular atrophy.
CONCLUSIONS: Our findings provide a deeper understanding of the physiological functions of T-type calcium channels in plant-parasitic nematodes. The T-type calcium channel can be considered a promising target for sustainable nematode management practices.

Effects of different winter paddock management of Thoroughbred weanlings and yearlings in Hokkaido, Japan, which is extremely cold in winter, on physiological function, endocrine function and growth were investigated. They were divided into two groups; those kept outdoors for 22 hr in the paddock (22hr group) and those kept outdoors for 7 hr in daytime with walking exercise for 1 hr using the horse-walker (7hr+W group), and the changes in daily distance travelled, body temperature (BT), heart rate (HR), HR variability (HRV), endocrine function and growth parameters were compared between the two groups from November at the year of birth to January at 1 year of age. The 7hr+W group could travel almost the same distance as the 22hr group by using the horse-walker. The 22hr group had a lower rate of increase in body weight than the 7hr+W group in January. In addition, lower in BT and HR were observed, and HRV analysis showed an increase in high frequency power spectral density, indicating that parasympathetic nervous activity was dominant. And also, changes in circulating cortisol and thyroxine were not observed despite cold environment. On the other hand, the 7hr+W group had higher prolactin and insulin like growth factor than the 22hr group in January, and cortisol and thyroxine were also increased. Physiological and endocrinological findings from the present study indicate that the management of the 7hr+W group is effective in promoting growth and maintaining metabolism during the winter season.

Sigmar1 is a ubiquitously expressed, multifunctional protein known for its cardioprotective roles in cardiovascular diseases. While accumulating evidence indicate a critical role of Sigmar1 in cardiac biology, its physiological function in the vasculature remains unknown. In this study, we characterized the expression of Sigmar1 in the vascular wall and assessed its physiological function in the vascular system using global Sigmar1 knockout (Sigmar1-/-) mice. We determined the expression of Sigmar1 in the vascular tissue using immunostaining and biochemical experiments in both human and mouse blood vessels. Deletion of Sigmar1 globally in mice (Sigmar1-/-) led to blood vessel wall reorganizations characterized by nuclei disarray of vascular smooth muscle cells, altered organizations of elastic lamina, and higher collagen fibers deposition in and around the arteries compared to wildtype littermate controls (Wt). Vascular function was assessed in mice using non-invasive time-transit method of aortic stiffness measurement and flow-mediated dilation (FMD) of the left femoral artery. Sigmar1-/- mice showed a notable increase in arterial stiffness in the abdominal aorta and failed to increase the vessel diameter in response to reactive-hyperemia compared to Wt. This was consistent with reduced plasma and tissue nitric-oxide bioavailability (NOx) and decreased phosphorylation of endothelial nitric oxide synthase (eNOS) in the aorta of Sigmar1-/- mice. Ultrastructural analysis by transmission electron microscopy (TEM) of aorta sections showed accumulation of elongated shaped mitochondria in both vascular smooth muscle and endothelial cells of Sigmar1-/- mice. In accordance, decreased mitochondrial respirometry parameters were found in ex-vivo aortic rings from Sigmar1 deficient mice compared to Wt controls. These data indicate a potential role of Sigmar1 in maintaining vascular homeostasis.

Ammonia is a major water quality factor influencing the survival and health of shrimp, among which the gill is the main effector organ for ammonia toxicity. In this study, we chose two types of Litopenaeus vannamei that were cultured in 30‱ seawater and domesticated in 3‱ low salinity, respectively, and then separately subjected to ammonia stress for 14 days under seawater and low-salinity conditions, of which the 3‱ low salinity-cultured shrimp were domesticated from the shrimp cultured in 30‱ seawater after 27 days of gradual salinity desalination. In detail, this study included four groups, namely the SC group (ammonia-N 0 mg/L, salinity 30‱), SAN group (ammonia-N 10 mg/L, salinity 30‱), LC group (ammonia-N 0 mg/L, salinity 3‱), and LAN group (ammonia-N 10 mg/L, salinity 3‱). The ammonia stress lasted for 14 days, and then the changes in the morphological structure and physiological function of the gills were explored. The results show that ammonia stress caused the severe contraction of gill filaments and the deformation or even rupture of gill vessels. Biochemical indicators of oxidative stress, including LPO and MDA contents, as well as T-AOC and GST activities, were increased in the SAN and LAN groups, while the activities of CAT and POD and the mRNA expression levels of antioxidant-related genes (nrf2, cat, gpx, hsp70, and trx) were decreased. In addition, the mRNA expression levels of the genes involved in ER stress (ire1 and xbp1), apoptosis (casp-3, casp-9, and jnk), detoxification (gst, ugt, and sult), glucose metabolism (pdh, hk, pk, and ldh), and the tricarboxylic acid cycle (mdh, cs, idh, and odh) were decreased in the SAN and LAN groups; the levels of electron-transport chain-related genes (ndh, cco, and coi), and the bip and sdh genes were decreased in the SAN group but increased in the LAN group; and the level of the ATPase gene was decreased but the cytc gene was increased in the SAN and LAN groups. The mRNA expression levels of osmotic regulation-related genes (nka-β, ca, aqp and clc) were decreased in the SAN group, while the level of the ca gene was increased in the LAN group; the nka-α gene was decreased in both two groups. The results demonstrate that ammonia stress could influence the physiological homeostasis of the shrimp gills, possibly by damaging the tissue morphology, and affecting the redox, ER function, apoptosis, detoxification, energy metabolism, and osmoregulation.

Glucagon-like peptide-1 (GLP-1), secreted by L cells in the small intestine, assumes a central role in managing type 2 diabetes mellitus (T2DM) and obesity. Its influence on insulin secretion and gastric emptying positions it as a therapeutic linchpin. However, the limited applicability of native GLP-1 stems from its short half-life, primarily due to glomerular filtration and the inactivating effect of dipeptidyl peptidase-IV (DPP-IV). To address this, various structural modification strategies have been developed to extend GLP-1\'s half-life. Despite the commendable efficacy displayed by current GLP-1 receptor agonists, inherent limitations persist. A paradigm shift emerges with the advent of unimolecular multi-agonists, such as the recently introduced tirzepatide, wherein GLP-1 is ingeniously combined with other gastrointestinal hormones. This novel approach has captured the spotlight within the diabetes and obesity research community. This review summarizes the physiological functions of GLP-1, systematically explores diverse structural modifications, delves into the realm of unimolecular multi-agonists, and provides a nuanced portrayal of the developmental prospects that lie ahead for GLP-1 analogs.

Phase separation, also known as biomolecule condensate, participates in physiological processes such as transcriptional regulation, signal transduction, gene expression, and DNA damage repair by creating a membrane-free compartment. Phase separation is primarily caused by the interaction of multivalent non-covalent bonds between proteins and/or nucleic acids. The strength of molecular multivalent interaction can be modified by component concentration, the potential of hydrogen, posttranslational modification, and other factors. Notably, phase separation occurs frequently in the cytoplasm of mitochondria, the nucleus, and synapses. Phase separation in vivo is dynamic or stable in the normal physiological state, while abnormal phase separation will lead to the formation of biomolecule condensates, speeding up the disease progression. To provide candidate suggestions for the clinical treatment of nervous system diseases, this review, based on existing studies, carefully and systematically represents the physiological roles of phase separation in the central nervous system and its pathological mechanism in neurodegenerative diseases.

Owing to renal reabsorption and the loss of uricase activity, uric acid (UA) is strictly maintained at a higher physiological level in humans than in other mammals, which provides a survival advantage during evolution but increases susceptibility to certain diseases such as gout. Although monosodium urate (MSU) crystal precipitation has been detected in different tissues of patients as a trigger for disease, the pathological role of soluble UA remains controversial due to the lack of causality in the clinical setting. Abnormal elevation or reduction of UA levels has been linked to some of pathological status, also known as U-shaped association, implying that the physiological levels of UA regulated by multiple enzymes and transporters are crucial for the maintenance of health. In addition, the protective potential of UA has also been proposed in aging and some diseases. Therefore, the role of UA as a double-edged sword in humans is determined by its physiological or non-physiological levels. In this review, we summarize biosynthesis, membrane transport, and physiological functions of UA. Then, we discuss the pathological involvement of hyperuricemia and hypouricemia as well as the underlying mechanisms by which UA at abnormal levels regulates the onset and progression of diseases. Finally, pharmacological strategies for urate-lowering therapy (ULT) are introduced, and current challenges in UA study and future perspectives are also described.

Whey, a major by-product of cheese production, is primarily composed of whey protein (WP). To mitigate environmental pollution, it is crucial to identify effective approaches for fully utilizing the functional components of whey or WP to produce high-value-added products. This review aims to illustrate the active substances with immunomodulatory, metabolic syndrome-regulating, antioxidant, antibacterial, and anti-inflammatory activities produced by whey or WP through fermentation processes, and summarizes the application and the effects of whey or WP on nutritional properties and health promotion in fermented foods. All these findings indicate that whey or WP can serve as a preservative, a source of high-protein dietary, and a source of physiologically active substance in the production of fermented foods. Therefore, expanding the use of whey or WP in fermented foods is of great importance for converting whey into value-added products, as well as reducing whey waste and potential contamination.

Nitrite and microplastics (MPs) are environmental pollutants that threaten intestinal integrity and affect immune function of shrimp. In this study, the shrimp Litopenaeus vannamei were exposed to the individual and combined stress of nitrite and microplastics for 14 days, and the changes of intestinal histology and physiological functions were investigated. After single and combined stress, affectations occurred in intestinal tissue; the antioxidant enzyme activities (MDA, H2O2, CAT increased) and gene expression levels (CAT, SOD, GPx, HSP70 up-regulated) changed. The expression levels of detoxification genes (CYP450, UGT down-regulated, GST up-regulated), apoptosis genes (CASP-3 up-regulated) and endoplasmic reticulum stress genes (Bip, GRP94 down-regulated) changed. Furthermore, the stress also increased intestinal microbial diversity, causing bacterial composition variation, especially beneficial bacteria and pathogenic bacteria. These results suggested that nitrite and microplastics stress had adverse effects on the intestinal health of L. vannamei by affecting intestinal tissue morphology, immune response and microbial community.