The Relationship between SNAP25 and Some Common Human Neurological Syndromes.

Over the years, research on the pathogenesis of neurological diseases has progressed slowly worldwide. However, as the incidence rate continues to increase and the disease gradually develops, early diagnosis and treatment have become a top priority. SANP25, a protein present on the presynaptic membrane and involved in neurotransmitter release, is closely related to the loss or abnormal expression of synapses and neurons. SNAP25 deficiency can lead to synaptic disorders and inhibit neurotransmitter release. Therefore, a large amount of literature believes that SNAP25 gene mutation is a risk factor for many neurological diseases. This review used advanced search on PubMed to conduct extensive article searches for relevant literature. The search keywords included SNAP25 and Alzheimer's disease, SNAP25 and Parkinson's disease, and so on. After reading and summarizing the previous papers, the corresponding conclusions were obtained to achieve the purpose of the review. The deficiency or variation of SNAP25 might be related to the onset of schizophrenia, epilepsy, attention deficit/hypoactivity disorder, bipolar disorder effective disorder, and autism. SNAP25 has been found to be used as a neuropathological marker for neurological diseases, which could be the target of diagnosis or treatment of Alzheimer's disease and Parkinson's disease. Cerebrospinal Fluid (CSF) or blood has been found to enable more effective drug development.

Association Between Peritoneal Glucose Absorption, Lipid Metabolism, and Cardiovascular Disease Risk in Nondiabetic Patients on Peritoneal Dialysis.

BACKGROUND: Excessive sugar intake increases the energy metabolic burden and the risk of cardiovascular disease (CVD). Patients on peritoneal dialysis absorb much more glucose than the World Health Organization recommends, but the link to CVD is unclear. OBJECTIVE: To identify the association between peritoneal glucose absorption, lipid metabolism, and CVD. METHODS: We applied generalized additive mixed effects and mixed effects Cox proportional hazard models to evaluate the impact of peritoneal glucose absorption on lipid profiles and CVD risk. We performed subgroup analyses by using protein intake (normalized protein nitrogen appearance [nPNA] and normalized protein catabolic rate [nPCR] were used to assess protein intake) and high-sensitivity C-reactive protein (hs-CRP). RESULTS: After multivariable adjustment, peritoneal glucose absorption per 10 g/d increase was associated with an increase in cholesterol of 0.145 (95% confidence interval [CI]: 0.086-0.204) mmol/L. No link with the total risk of CVD was observed; however, protein intake and hs-CRP levels affected the relationship between glucose absorption and CVD risk. Patients with values for nPNA and nPCR <1.0 g/(kg·d) were associated with a lower risk of CVD (hazard ratio [HR] 95% CI: 0.68 (0.46-0.98)) with glucose absorption per 10 g/d increase. While patients with hs-CRP levels ≥3 mg/d or values for nPNA or nPCR ≥1.0 g/(kg·d) were associated with a higher risk of CVD (HR 95% CI: 1.32 (1.07-1.63); 1.31 (1.02-1.68)) for glucose absorption per 10 g/d increase. CONCLUSIONS: Our study found a positive correlation between peritoneal glucose absorption and lipid profiles. Increased glucose absorption was associated with a lower risk of CVD in lower protein intake patients and a higher risk of CVD in higher hs-CRP or protein intake levels in patients on peritoneal dialysis.

Melatonin improves mouse oocyte quality from 2-ethylhexyl diphenyl phosphate-induced toxicity by enhancing mitochondrial function.

2-Ethylhexyl diphenyl phosphate (EHDPP) is a representative organophosphorus flame retardant (OPFR) that has garnered attention due to its widespread use and potential adverse effects. EHDPP exhibits cytotoxicity, genotoxicity, developmental toxicity, and endocrine disruption. However, the toxicity of EHDPP in mammalian oocytes and the underlying mechanisms remain poorly understood. Melatonin is a natural free radical scavenger that has demonstrated cytoprotective properties. In this study, we investigated the effect of EHDPP on mouse oocytes in vitro culture system and evaluated the rescue effect of melatonin on oocytes exposed to EHDPP. Our results indicated that EHDPP disrupted oocyte maturation, resulting in the majority of oocytes arrested at the metaphase I (MI) stage, accompanied by cytoskeletal damage and elevated levels of reactive oxygen species (ROS). Nevertheless, melatonin supplementation partially rescued EHDPP-induced mouse oocyte maturation impairment. Results of single-cell RNA sequencing (scRNA-seq) analysis elucidated potential mechanisms underlying these protective effects. According to the results of scRNA-seq, we conducted further tests and found that EHDPP primarily disrupts mitochondrial distribution and function, kinetochore-microtubule (K-MT) attachment, DNA damage, apoptosis, and histone modification, which were rescued upon the supplementation of melatonin. This study reveals the mechanisms of EHDPP on female reproduction and indicates the efficacy of melatonin as a therapeutic intervention for EHDPP-induced defects in mouse oocytes.

High-intensity interval training ameliorates postnatal immune activation-induced mood disorders through KDM6B-regulated glial activation.

Postnatal immune activation (PIA) induces persistent glial activation in the brain and causes various neuropathologies in adults. Exercise training improves stress-related mood disorders; however, the role of exercise in psychiatric disorders induced by early-life immune activation and the association between exercise training and glial activation remain unclear. We compared the effects of different exercise intensities on the PIA model, including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Both HIIT and MICT in adolescent mice inhibited neuroinflammation, remodeled synaptic plasticity, and improved PIA-induced mood disorders in adulthood. Importantly, HIIT was superior to MICT in terms of reducing inflammation and increasing body weight. RNA-seq of prefrontal cortex (PFC) tissues revealed a gene expression pattern, confirming that HIIT was more effective than MICT in improving brain glial cell activation through epigenetic modifications of KDM6B. We investigated the role of KDM6B, a specific histone lysine demethylation enzyme - histone 3 lysine 27 demethylase, in inhibiting glial activation against PIA-induced depression and anxiety by regulating the expression of IL-4 and brain-derived neurotrophic factor (BDNF). Overall, our data support the idea that HIIT improves PIA-induced mood disorders by regulating KDM6B-mediated epigenetic mechanisms and indicate that HIIT might be superior to MICT in improving mood disorders with PIA in mice. Our findings provide new insights into the treatment of anxiety and depression disorders.

Nicotinamide mononucleotide maintains cytoskeletal stability and fortifies mitochondrial function to mitigate oocyte damage induced by Triocresyl phosphate.

Triocresyl phosphate (TOCP) was commonly used as flame retardant, plasticizer, lubricant, and jet fuel additive. Studies have shown adverse effects of TOCP on the reproductive system. However, the potential harm brought by TOCP, especially to mammalian female reproductive cells, remains a mystery. In this study, we employed an in vitro model for the first time to investigate the effects of TOCP on the maturation process of mouse oocytes. TOCP exposure hampered the meiotic division process, as evidenced by a reduction in the extrusion of the first polar body from oocytes. Subsequent research revealed the disruption of the oocyte cell cytoskeleton induced by TOCP, resulting in abnormalities in spindle organization, chromosome alignment, and actin filament distribution. This disturbance further extended to the rearrangement of organelles within oocytes, particularly affecting the mitochondria. Importantly, after TOCP treatment, mitochondrial function in oocytes was impaired, leading to oxidative stress, DNA damage, cell apoptosis, and subsequent changes of epigenetic modifications. Supplementation with nicotinamide mononucleotide (NMN) alleviated the harmful effects of TOCP. NMN exerted its mitigating effects through two fundamental mechanisms. On one hand, NMN conferred stability to the cell cytoskeleton, thereby supporting nuclear maturation. On the other hand, NMN enhanced mitochondrial function within oocytes, reducing the excess reactive oxygen species (ROS), restoring meiotic division abnormalities caused by TOCP, preventing oocyte DNA damage, and suppressing epigenetic changes. These findings not only enhance our understanding of the molecular basis of TOCP induced oocyte damage but also offer a promising avenue for the potential application of NMN in optimizing reproductive treatment strategies.

Segmentation of bone surface from ultrasound using a lightweight network UBS-Net.

Objective. Ultrasound-assisted orthopaedic navigation held promise due to its non-ionizing feature, portability, low cost, and real-time performance. To facilitate the applications, it was critical to have accurate and real-time bone surface segmentation. Nevertheless, the imaging artifacts and low signal-to-noise ratios in the tomographical B-mode ultrasound (B-US) images created substantial challenges in bone surface detection. In this study, we presented an end-to-end lightweight US bone segmentation network (UBS-Net) for bone surface detection.Approach. We presented an end-to-end lightweight UBS-Net for bone surface detection, using the U-Net structure as the base framework and a level set loss function for improved sensitivity to bone surface detectability. A dual attention (DA) mechanism was introduced at the end of the encoder, which considered both position and channel information to obtain the correlation between the position and channel dimensions of the feature map, where axial attention (AA) replaced the traditional self-attention (SA) mechanism in the position attention module for better computational efficiency. The position attention and channel attention (CA) were combined with a two-class fusion module for the DA map. The decoding module finally completed the bone surface detection.Main Results. As a result, a frame rate of 21 frames per second (fps) in detection were achieved. It outperformed the state-of-the-art method with higher segmentation accuracy (Dice similarity coefficient: 88.76% versus 87.22%) when applied the retrospective ultrasound (US) data from 11 volunteers.Significance. The proposed UBS-Net for bone surface detection in ultrasound achieved outstanding accuracy and real-time performance. The new method out-performed the state-of-the-art methods. It had potential in US-guided orthopaedic surgery applications.

Medium-Entropy Monosilicates Deliver High Corrosion Resistance to Calcium-Magnesium Aluminosilicate Molten Salt.

For decreasing the global cost of corrosion, it is essential to understand the intricate mechanisms of corrosion and enhance the corrosion resistance of materials. However, the ambiguity surrounding the dominant mechanism of calcium-magnesium aluminosilicate (CMAS) molten salt corrosion in extreme environments hinders the mix-and-matching of the key rare earth elements for increasing the resistance of monosilicates against corrosion of CMAS. Herein, an approach based on correlated electron microscopy techniques combined with density functional theory calculations is presented to elucidate the complex interplay of competing mechanisms that control the corrosion of CMAS of monosilicates. These findings reveal a competition between thermodynamics and kinetics that relies on the temperatures and corrosion processes. Innovative medium-entropy monosilicates with exceptional corrosion resistance even at 1500 °C are developed. This is achieved by precisely modulating the radii of rare earth ions in monosilicates to strike a delicate balance between the competition in thermodynamics and kinetics. After 50 and 100 h of corrosion, the thinnest reactive layers are measured to be only 28.8 and 35.4 µm, respectively.

Microdrill Versus Diode Laser in Endoscopic Stapedotomy: A Comparative Study.

BACKGROUND: Microdrill and diode laser are two different methods used in endoscopic stapedotomy for otosclerosis. These two methods have not been compared in endoscopic stapedotomy. AIMS/OBJECTIVES: To analyze the differences between microdrill and diode laser in endoscopic stapedotomy for otosclerosis. MATERIALS AND METHODS: This is a randomized clinical trial; patients with otosclerosis were randomly divided into microdrill group (group A: n = 69) and diode laser group (group B: n = 62). Differences between the two groups were then compared. RESULTS: The preoperative air-bone gap (ABG) was 25.40 ± 10.88 dBHL in group A and 24.84 ± 12.23 dBHL in group B, with no significant between-group difference ( p > 0.05). The postoperative ABG in group A was 13.27 ± 9.91 dBHL versus 11.79 ± 10.82 dBHL in group B, and there was no significant difference between the groups ( p > 0.05). The surgical time in group B (64 ± 31.23 minutes) was significantly longer than that in group A (48 ± 25.62 minutes) ( p = 0.02). There were no significant between-group differences in basic patient-related data, preoperative air conduction (AC), preoperative bone conduction (BC), postoperative AC, distribution of postoperative ABG, preoperative ABG at different frequencies, and postoperative ABG at different frequencies. There was also no significant between-group difference in the average bleeding volume or number of patients with postoperative dizziness. CONCLUSION AND SIGNIFICANCE: The postoperative improvement in hearing level in the two group was equivalent, but group A had the advantage of a shorter operation time. LEVEL OF EVIDENCE: 4.

Risks of mental disorders among inpatients with burn injury: A nationwide cohort study.

OBJECTIVE: This investigation identified the association between burn injuries and the risk of mental disorders in patients with no documented pre-existing psychiatric comorbidities. We also examined the relationship of injury severity and the types of injury with the likelihood of receiving new diagnoses of mental disorders. METHODS: This population-based retrospective cohort study used administrative data extracted from the Taiwanese National Health Insurance Research Database (NHIRD) between 2000 and 2013. In total, 10,045 burn survivors were matched with a reference cohort of 40,180 patients without burn injuries and were followed to determine if any mental disorder was diagnosed. Patients diagnosed with mental disorders in the five years before study initiation were excluded to ensure incident diagnoses throughout the research duration. Generalized estimating equations in Cox proportional hazard regression models were used for data analysis. RESULTS: In general, burn injury survivors have a 1.21-fold risk of being diagnosed with new mental disorders relative to patients without burn injuries. Total body surface area (TBSA) of ≧ 30% (aHR: 1.49, 95% CI: 1.36-1.63) and third- or fourth-degree burns (aHR: 1.49, 95% CI: 1.37-1.63) had a significantly greater risk of being diagnosed with mental disorders in comparison to the reference cohort. Patients TBSA 10-29% (aHR: 0.85, 95% CI: 0.77-0.93) and first- or second-degree burn victims (aHR: 0.89, 95% CI: 0.81-0.97) had relatively lower risk of mental disorders than the reference cohort. CONCLUSION: Burn injuries were associated with an increased risk of mental disorders. Additional research in this field could elucidate this observation, especially if the inherent limitations of the NHIRD can be overcome.

Cyclophosphamide activates ferroptosis-induced dysfunction of Leydig cells via SMAD2 pathway†.

Cyclophosphamide (CP) is a widely used chemotherapeutic drug and immunosuppressant in the clinic, and the hypoandrogenism caused by CP is receiving more attention. Some studies found that ferroptosis is a new mechanism of cell death closely related to chemotherapeutic drugs and plays a key role in regulating reproductive injuries. The purpose of this study is to explore ferroptosis' role in testicular Leydig cell dysfunction and molecular mechanisms relating to it. In this study, the level of ferroptosis in the mouse model of testicular Leydig cell dysfunction induced by CP was significantly increased and further affected testosterone synthesis. The ferroptosis inhibitors ferrostatin-1 (Fer-1) and iron chelator deferoxamine (DFO) can improve injury induced by CP. The results of immunohistochemistry showed that Fer-1 and DFO could improve the structural disorder of seminiferous tubules and the decrease of the number of Leydig cells in testicular tissue induced by CP. Immunofluorescence and western blot confirmed that Fer-1 and DFO could improve the expression of key enzymes in testosterone synthesis. The activation of SMAD family member 2 (Smad2)/cyclin-dependent kinase inhibitor 1A (Cdkn1a) pathway can improve the ferroptosis of Leydig cells induced by CP and protect the function of Leydig cells. By inhibiting the Smad2/Cdkn1a signal pathway, CP can regulate ferroptosis, resulting in testicular Leydig cell dysfunction. In this study, CP-induced hypoandrogenism is explained theoretically and a potential therapeutic strategy is provided.

Comparison of capture-based mtDNA sequencing performance between MGI and illumina sequencing platforms in various sample types.

BACKGROUND: Mitochondrial genome abnormalities can lead to mitochondrial dysfunction, which in turn affects cellular biology and is closely associated with the development of various diseases. The demand for mitochondrial DNA (mtDNA) sequencing has been increasing, and Illumina and MGI are two commonly used sequencing platforms for capture-based mtDNA sequencing. However, there is currently no systematic comparison of mtDNA sequencing performance between these two platforms. To address this gap, we compared the performance of capture-based mtDNA sequencing between Illumina's NovaSeq 6000 and MGI's DNBSEQ-T7 using tissue, peripheral blood mononuclear cell (PBMC), formalin-fixed paraffin-embedded (FFPE) tissue, plasma, and urine samples. RESULTS: Our analysis indicated a high degree of consistency between the two platforms in terms of sequencing quality, GC content, and coverage. In terms of data output, DNBSEQ-T7 showed higher rates of clean data and duplication compared to NovaSeq 6000. Conversely, the amount of mtDNA data obtained by per gigabyte sequencing data was significantly lower in DNBSEQ-T7 compared to NovaSeq 6000. In terms of detection mtDNA copy number, both platforms exhibited good consistency in all sample types. When it comes to detection of mtDNA mutations in tissue, FFPE, and PBMC samples, the two platforms also showed good consistency. However, when detecting mtDNA mutations in plasma and urine samples, significant differenceof themutation number detected was observed between the two platforms. For mtDNA sequencing of plasma and urine samples, a wider range of DNA fragment size distribution was found in NovaSeq 6000 when compared to DNBSEQ-T7. Additionally, two platforms exhibited different characteristics of mtDNA fragment end preference. CONCLUSIONS: In summary, the two platforms generally showed good consistency in capture-based mtDNA sequencing. However, it is necessary to consider the data preferences generated by two sequencing platforms when plasma and urine samples were analyzed.

Generation of a Hydrophobic Protrusion on Nanoparticles to Improve the Membrane-Anchoring Ability and Cellular Internalization.

Controlling the nanoparticle-cell membrane interaction to achieve easy and fast membrane anchoring and cellular internalization is of great importance in a variety of biomedical applications. Here we report a simple and versatile strategy to maneuver the nanoparticle-cell membrane interaction by creating a tunable hydrophobic protrusion on Janus particles through swelling-induced symmetry breaking. When the Janus particle contacts cell membrane, the protrusion will induce membrane wrapping, leading the particles to docking to the membrane, followed by drawing the whole particles into the cell. The efficiencies of both membrane anchoring and cellular internalization can be promoted by optimizing the size of the protrusion. In vitro, the Janus particles can quickly anchor to the cell membrane in 1 h and be internalized within 24 h, regardless of the types of cells involved. In vivo, the Janus particles can effectively anchor to the brain and skin tissues to provide a high retention in these tissues after intracerebroventricular, intrahippocampal, or subcutaneous injection. This strategy involving the creation of a hydrophobic protrusion on Janus particles to tune the cell-membrane interaction holds great potential in nanoparticle-based biomedical applications.

Pedicle screw path planning for multi-level vertebral fixation.

BACKGROUND: For the spinal internal fixation procedures, connecting rods to the pedicle screws are commonly used in all spinal segments from the cervical to sacral spine. So far, we have only seen single vertebral screw trajectory planning methods in literatures. Joint screw placements in multi-level vertebrae with the constraint of an ipsilateral connecting rod are not considered. PURPOSE: In this paper, a screw trajectory planning method that considers screw-rod joint system with both multi-level vertebral constraints and individual vertebral safety tolerance are proposed. METHODS: The proposed method addresses three challenging constraints jointly for multi-level vertebral fixation with pedicle screws. First, a cylindrical screw safe passage model is suggested instead of a unique mathematical optimal trajectory for a single pedicle. Second, the flexible screw cap accessibility model is also included. Third, the connecting rod is modeled to accommodate the spine contour and support the needed gripping capacity. The retrospective clinical data of relative normal shape spines from Beijing Jishuitan hospital were used in the testing. The screw trajectories from the existing methods based on single vertebra and the proposed method based on multi-level vertebrae optimization are calculated and compared. RESULTS: The results showed that the calculated screw placements by the proposed method can achieve 88% success rate without breaking the pedicle cortex and 100% in clinical class A quality (allow less than 2 mm out of the pedicle cortex) compared to 86.1% and 99.1%, respectively, with the existing methods. Expert evaluation showed that the screw path trajectories and the connecting rod calculated by the new method satisfied the clinical implantation requirements. CONCLUSIONS: The new screw planning approach that seeks an overall optimization for multi-level vertebral fixation is feasible and more advantageous for clinical use than the single vertebral approaches.

The arsenic-lowering effect of inulin-type prebiotics in end-stage renal disease: a randomized crossover trial.

Background: Circulatory imbalance of trace elements is frequent in end-stage renal disease (ESRD), leading to a deficiency of essential elements and excess of toxic elements. The present study aimed to investigate whether inulin-type fructans (ITFs) could ameliorate the circulatory imbalance by modulating gut microbiota and regulating the absorption and elimination of trace elements. Methods: Peritoneal dialysis patients were enrolled in a randomized crossover trial, undergoing interventions with ITFs (10 g d-1) and maltodextrin (placebo) over a 9-month period (with a 3-month washout). The primary outcomes included essential elements Mn, Fe, Co, Cu, Zn, Se, Sr, and Mo and potential toxic elements V, Cr, Ni, As, Cd, Ba, Tl, Pb, Th, and U in plasma. Secondary outcomes included the gut microbiome, short chain fatty acids (SCFAs), bile acids (BAs), and daily removal of trace elements through urine, dialysate and feces. Results: Among the 44 participants initially randomized, 29 completed the prebiotic, placebo or both interventions. The daily dietary intake of macronutrients and trace elements remained consistent throughout the study. The administration of 10 g d-1 ITFs significantly reduced plasma arsenic (As) by 1.03 µg L-1 (95%CI: -1.74, -0.33) (FDR-adjusted P = 0.045) down from the baseline of 3.54 µg L-1 (IQRs: 2.61-4.40) and increased the As clearance rate by urine and dialysis (P = 0.033). Positive changes in gut microbiota were also observed, including an increase in the Firmicutes/Bacteroidetes ratio (P = 0.050), a trend towards higher fecal SCFAs (P = 0.082), and elevated excretion of primary BAs (P = 0.035). However, there were no significant changes in plasma concentrations of other trace elements or their daily removal by urine, dialysis and feces. Conclusions: The daily administration of 10 g d-1 ITFs proved to be effective in reducing the circulating retention of As but demonstrated to be ineffective for other trace elements in ESRD. These sentences are ok to include but as "The clinical trial registry number is ChiCTR-INR-17013739 (https://www.chictr.org.cn/showproj.aspx?proj=21228)".

Shear banding in monodisperse polymer melt.

We performed a series of molecular dynamics simulations on monodisperse polymer melts to investigate the formation of shear banding. Under high shear rates, shear banding occurs, which is intimately accompanied by the entanglement heterogeneity. Interestingly, the same linear relationship between the end-to-end distance Ree and entanglement density Z is observed at homogeneous flow before the onset of shear banding and at the shear banding state, where Ree ∼ ln(Wi0.87)-ξ0Z is proposed as the criterion to describe the dynamic force balance of the molecular chain in flow with a high rate. Deviating from this relation leads to a force imbalance and results in the emergence of shear banding. We establish a scaling relation between the disentanglement rate Vd and the Weissenberg number Wi as Vd∼Wi0.87 for stable flow in homogeneous shear and shear banding states. The formation of shear banding prevents chains from further stretching and disentanglement. The transition from homogeneous shear to shear banding partially dissipates the increased free energy from shear and reduces the free energy of the system.

Kaempferol ameliorated alcoholic liver disease through inhibiting hepatic bile acid synthesis by targeting intestinal FXR-FGF15 signaling.

BACKGROUND: Alcoholic liver disease (ALD) is characterized by the disturbance of bile acids homeostasis, which further deteriorates ALD. Bile acid metabolism and its related signal molecules have become new therapeutic targets for alcoholic liver disease. This study aimed to investigate the impact of kaempferol (KAE) on ALD and elucidate its underlying mechanisms. METHODS: C57BL/6 N mice were utilized to establish Binge-on-Chronic alcohol exposure mice model. KAE was administered as an interventional drug to chronic alcohol-fed mice for four weeks to assess its effects on liver damage and bile acid metabolism. And Z-Guggulsterone (Z-Gu), a global FXR inhibitor, was used to investigate the impact of intestinal FXR-FGF15 signal in ALD mice. Additionally, intestinal epithelial cells were exposed to alcohol or specific bile acid to induce the damage of FXR activity in vitro. The dual luciferase activity assay was employed to ascertain the interplay between KAE and FXR activity. RESULTS: The results indicated that KAE treatment exhibited a significant hepatoprotective effect against chronic alcohol-fed mice. Accompanied by the intestinal FXR activation, the administration of KAE suppressed hepatic bile acid synthesis and promoted intestinal bile acid excretion in chronic ALD mice. And the notable alterations in total bile acid levels and composition were observed in mice after chronic alcohol feeding, which were reversed by KAE supplementation. And more, the protective effects of KAE on ALD mice were deprived by the inhibition of intestinal FXR activation. In vitro experiments demonstrated that KAE effectively activated FXR-FGF15 signaling, mitigated the damage to FXR activity in intestinal epithelial cells caused by alcohol or specific bile acids. Additionally, luciferase activity assays revealed that KAE directly promoted FXR expression, thereby enhancing FXR activity. CONCLUSION: KAE treatment inhibited hepatic bile acids synthesis, maintained bile acids homeostasis in ALD mice by directly activating intestinal FXR-FGF15 signaling, which effectively alleviated liver injury induced by chronic alcohol consumption.

Bond Orientation-Determined Enthalpic Stress in Polymer Glasses upon Deformation.

The mechanical properties of polymer glass are determined by both intermolecular local packing structures and aligned intrachain configurations. These configurations involve multiple space scales, and the underlying mechanism is not well understood yet. By applying mechanical stimulation to cold-drawn polymer glasses, the present simulation work shows a one-to-one correspondence between arising retractive stress and the segment orientation parameter on the length scale of the intrachain connecting bond. Such retractive stress is a newly produced enthalpic stress when segment orientation on the length scale of bonds and particle mobility coexist. This reveals a potential mechanism of how the intrachain orientation on the length scale of bonds influences the mechanical behaviors of polymer glasses.

Cyclic Peptides from the Opportunistic Pathogen Basidiobolus meristosporus.

Three new cyclic peptides, meristosporins A, B, and C (1-3), one of which features an unusual amino acid, were isolated from the opportunistic pathogen Basidiobolus meristosporus and identified by 1D, 2D NMR, MS/MS, and Marfey's analysis. The biosynthetic pathway of the hexapeptide meristosporin A (1) was deduced based on nonribosomal peptide synthetase gene clusters analysis. Compounds 1 and 2 showed cytotoxicity to RAW264.7 and 293T cells, respectively. These compounds may be involved in the fungal injury caused to human cells.

Dynamic Metal Nanoclusters: A Review on Accurate Crystal Structures.

Dynamic metal nanoclusters have garnered widespread attention due to their unique properties and potential applications in various fields. Researchers have been dedicated to developing new synthesis methods and strategies to control the morphologies, compositions, and structures of metal nanoclusters. Through optimized synthesis methods, it is possible to prepare clusters with precise sizes and shapes, providing a solid foundation for subsequent research. Accurate determination of their crystal structures is crucial for understanding their behavior and designing custom functional materials. Dynamic metal nanoclusters also demonstrate potential applications in catalysis and optoelectronics. By manipulating the sizes, compositions, and surface structures of the clusters, efficient catalysts and optoelectronic materials can be designed and synthesized for various chemical reactions and energy conversion processes. This review summarizes the research progress in the synthesis methods, crystal structure characterization, and potential applications of dynamic metal nanoclusters. Various nanoclusters composed of different metal elements are introduced, and their potential applications in catalysis, optics, electronics, and energy storage are discussed. Additionally, the important role of dynamic metal nanoclusters in materials science and nanotechnology is explored, along with an overview of the future directions and challenges in this field.