Structural insights into the substrate uptake and inhibition of the human creatine transporter (hCRT).

Creatine plays a vital role in cellular energy production and adenosine triphosphate (ATP) homeostasis and has also been identified as a neurotransmitter in the mammalian brain. Creatine is transported into cells by the human creatine transporter (hCRT) (SLC6A8), an Na/Cl-dependent symporter encoded on the X chromosome. Mutations in hCRT cause cerebral creatine deficiency syndrome 1, a neurological disorder marked by intellectual disability, speech delay, and seizures.

Natural peptidoglycan nanoparticles enable rapid antigen purification and potent delivery of plant-derived vaccines.

Plant molecular farming is a promising platform for biopharmaceutical production, however, downstream processing remains a challenge due to cost and complexity. In this study, we present natural peptidoglycan nanoparticles (NPNs) derived from Gram-positive lactic acid bacteria as a novel tool for plant-based vaccine purification and delivery. Sequential treatment with trichloroacetic acid and trypsin effectively reduced NPN size, removing residual host subcellular constructs and proteins while preserving protein-binding capacity.

Effects of different lactic acid bacteria fermentation on active substances and functional characteristics of honeysuckle liquid: analysis of metabolites of honeysuckle liquid based on metabolomics.

In order to study the effects of lactic acid bacteria on the active substances and functions of honeysuckle, metabolomics was used to analyze the differential metabolites of honeysuckle fermented by lactic acid bacteria. The results showed that increased the contents of total phenols, flavonoids and chlorogenic acid by 26.48, 22.

Impact of fermentation on the processing and digestion characteristics of honeysuckle polyphenols by .

The technology and digestive characteristics of honeysuckle beverages fermented by were researched, the digestive characteristics were evaluated by simulating the gastrointestinal digestive system . The optimum conditions were as follows: fermentation temperature, 35°C; fermentation time, 19 h; and inoculation amount, 3%. Fermented honeysuckle beverages had greater antioxidant and -glucosidase inhibition capacities than unfermented beverages after digestion.

Structural basis for the reaction cycle and transport mechanism of human Na-sulfate cotransporter NaS1 (SLC13A1).

Sulfate (SO) is a pivotal inorganic anion with essential roles in mammalian physiology. NaS1, a member of solute carrier 13 family and divalent anion/sodium symporter family, functions as a Na-sulfate cotransporter, facilitating sulfate (re)absorption across renal proximal tubule and small intestine epithelia. While previous studies have linked several human disorders to mutations in the gene, its transport mechanism remains unclear.

Molecular architecture of the mammalian 2-oxoglutarate dehydrogenase complex.

The 2-oxoglutarate dehydrogenase complex (OGDHc) orchestrates a critical reaction regulating the TCA cycle. Although the structure of each OGDHc subunit has been solved, the architecture of the intact complex and inter-subunit interactions still remain unknown. Here we report the assembly of native, intact OGDHc from Sus scrofa heart tissue using cryo-electron microscopy (cryo-EM), cryo-electron tomography (cryo-ET), and subtomogram averaging (STA) to discern native structures of the whole complex and each subunit.

Zeaxanthin dipalmitate-enriched wolfberry extract improves vision in a mouse model of photoreceptor degeneration.

Zeaxanthin dipalmitate (ZD) is a chemical extracted from wolfberry that protects degenerated photoreceptors in mouse retina. However, the pure ZD is expensive and hard to produce. In this study, we developed a method to enrich ZD from wolfberry on a production line and examined whether it may also protect the degenerated mouse retina.

Characterization of sensory and motor dysfunction and morphological alterations in late stages of type 2 diabetic mice.

Diabetic neuropathy is the most common complication of diabetes and lacks effective treatments. Although sensory dysfunction during the early stages of diabetes has been extensively studied in various animal models, the functional and morphological alterations in sensory and motor systems during late stages of diabetes remain largely unexplored. In the current work, we examined the influence of diabetes on sensory and motor function as well as morphological changes in late stages of diabetes.

Benefits and risks of PD-1/PD-L1 inhibitors for recurrent small cell lung cancer: A systematic review and meta-analysis.

The development of immune checkpoint inhibitors(ICIs) has revolutionized the progress of solid tumors. Ongoing clinical trials are exploring the use of checkpoint inhibitors in recurrent small-cell lung cancer and achieving specific results. Although studies have been conducted to systematically review this issue, we conducted this single-arm meta-analysis in light of the emergence of several new clinical studies.

Molecular basis for the catalytic mechanism of human neutral sphingomyelinases 1 (hSMPD2).

Enzymatic breakdown of sphingomyelin by sphingomyelinase (SMase) is the main source of the membrane lipids, ceramides, which are involved in many cellular physiological processes. However, the full-length structure of human neutral SMase has not been resolved; therefore, its catalytic mechanism remains unknown. Here, we resolve the structure of human full-length neutral SMase, sphingomyelinase 1 (SMPD2), which reveals that C-terminal transmembrane helices contribute to dimeric architecture of hSMPD2 and that D111 - K116 loop domain is essential for substrate hydrolysis.

Negative Life Events on Depression of Vocational Undergraduates in the Partial Least Squares Structural Equation Modeling Approach Perspective: A Mediated Moderation Model.

Background: Following China's strategy of developing applied and compound social talents, vocational undergraduates are surging rapidly, and it is essential to understand the causes of their depression to effectively prevent and intervene in schools.

Objective: We aimed to investigate the relationship between negative life events (NLEs) and depression among vocational undergraduates in China, along with the mediating role of loneliness and the moderating role of socioeconomic status (SES).

Methods: A convenience sample survey was conducted at a vocational education university ( = 1487), and analyzed using partial least squares structural equation modeling.

Research on river water quality evaluation based on the GA-PP and improved fuzzy model.

To ensure the water quality of rivers, it is crucial to scientifically evaluate their water quality status. This study takes a river in Jiangsu, China, as an example to establish six targeted main indicators for river water quality evaluation and uses a projection pursuit model optimized by the genetic algorithm to determine weights. Applying the improved fuzzy evaluation model to the final evaluation of water quality, the results indicate that this article adopts a weight calculation model that reduces dimensionality without losing data features, and the comprehensive evaluation model is also more complete, resulting in more accurate evaluation results.

Structural basis for recruitment of TASL by SLC15A4 in human endolysosomal TLR signaling.

Toll-like receptors (TLRs) are a class of proteins that play critical roles in recognizing pathogens and initiating innate immune responses. TASL, a recently identified innate immune adaptor protein for endolysosomal TLR7/8/9 signaling, is recruited by the lysosomal proton-coupled amino-acid transporter SLC15A4, and then activates IRF5, which in turn triggers the transcription of type I interferons and cytokines. Here, we report three cryo-electron microscopy (cryo-EM) structures of human SLC15A4 in the apo monomeric and dimeric state and as a TASL-bound complex.

A conformation-locking inhibitor of SLC15A4 with TASL proteostatic anti-inflammatory activity.

Dysregulation of pathogen-recognition pathways of the innate immune system is associated with multiple autoimmune disorders. Due to the intricacies of the molecular network involved, the identification of pathway- and disease-specific therapeutics has been challenging. Using a phenotypic assay monitoring the degradation of the immune adapter TASL, we identify feeblin, a chemical entity which inhibits the nucleic acid-sensing TLR7/8 pathway activating IRF5 by disrupting the SLC15A4-TASL adapter module.

Molecular basis of ClC-6 function and its impairment in human disease.

ClC-6 is a late endosomal voltage-gated chloride-proton exchanger that is predominantly expressed in the nervous system. Mutated forms of ClC-6 are associated with severe neurological disease. However, the mechanistic role of ClC-6 in normal and pathological states remains largely unknown.

Comparing Depression Prevalence and Associated Symptoms with Intolerance of Uncertainty among Chinese Urban and Rural Adolescents: A Network Analysis.

The prevalence of depression among adolescents is increasing, which can hinder their healthy development and is intricately linked to the intolerance of uncertainty (IU). IU involves both prospective anxiety and inhibitory anxiety. However, the precise relationship between depressive symptoms and these two components of IU remains unclear, particularly when considering the specific context of rural adolescents in China.

Intolerance of uncertainty fuels preservice teachers' smartphone dependence through rumination and anxiety during the COVID-19 pandemic: A cross-sectional study.

Objectives: We aimed to explore the relationship among intolerance of uncertainty (IU), rumination, anxiety, and smartphone dependence (SPD) in preservice teachers during the COVID-19 pandemic.

Methods: Two cross-sectional studies were conducted with Chinese preservice teachers, using questionnaires on IU, rumination, anxiety, and SPD. Data were analyzed using AMOS 24.

Soil enzyme activities, soil physical properties, photosynthetic physical characteristics and water use of winter wheat after long-term straw mulch and organic fertilizer application.

Introduction: Inappropriate residue and nutrient management leads to soil degradation and the decline of soil quality and water storage capacity.

Methods: An ongoing field experiment has been conducted since 2011 to investigate the effects of straw mulching (SM), and straw mulching combined with organic fertilizer (SM+O), on winter wheat yield, including a control treatment (CK, no straw). We studied the effects of these treatments on soil microbial biomass nitrogen and carbon, soil enzyme activity in 2019, photosynthetic parameters, evapotranspiration (ET), water use efficiency (WUE), and yields over five consecutive years (2015-2019).

Recent progress and challenges in the treatment of spinal cord injury.

Spinal cord injury (SCI) disrupts the structural and functional connectivity between the higher center and the spinal cord, resulting in severe motor, sensory, and autonomic dysfunction with a variety of complications. The pathophysiology of SCI is complicated and multifaceted, and thus individual treatments acting on a specific aspect or process are inadequate to elicit neuronal regeneration and functional recovery after SCI. Combinatory strategies targeting multiple aspects of SCI pathology have achieved greater beneficial effects than individual therapy alone.

Effect of long term application of super absorbent polymer on soil structure, soil enzyme activity, photosynthetic characteristics, water and nitrogen use of winter wheat.

Introduction: Water scarcity and seasonal drought are major constraints on agricultural development globally. Super absorbent polymer (SAP) is a good amendment that can improve soil structure, increase soil water retention, and promote crop growth even with less soil moisture. We hypothesize that long term application of SAP has a better effect on soil organic carbon, soil enzyme activity, photosynthetic characteristics, yield, and water and nitrogen use than short term application.

The influence of gratitude on pre-service teachers' career goal self-efficacy: Chained intermediary analysis of meaning in life and career calling.

Objective: The aim of the study was to explore the relationship among gratitude, meaning in life (MIL), career calling, and career goal self-efficacy (CGSE) of the pre-service teachers in the Free Teacher Education program in China and the internal mechanism of action.

Methods: In this study, gratitude, MIL, career calling, and CGSE questionnaires were used to investigate 801 pre-service teachers. IBM SPSS 25.