Association of cardiovascular health metrics with all-cause and cardiovascular disease mortality in chronic kidney disease: A cohort study.

BACKGROUND AND AIMS: Since the global burden of chronic kidney disease (CKD) is rising rapidly, the study aimed to assess the association of cardiovascular health (CVH) metrics with all-cause and cardiovascular disease (CVD) mortality among individuals with CKD. METHODS AND RESULTS: The cohort study included 5834 participants with CKD from the National Health and Nutrition Examination Survey 1999-2018. A composite CVH score was calculated based on smoking status, physical activity, body mass index, blood pressure, total cholesterol, diet quality, and glucose control. Primary outcomes were all-cause and CVD mortality as of December 31, 2019. Multivariable-adjusted Cox proportional hazards models were used to estimate the association between CVH metrics and deaths in CKD patients. During a median follow-up of 7.2 years, 2178 all-cause deaths and 779 CVD deaths were documented. Compared to participants with ideal CVH, individuals with intermediate CVH exhibited a 46.0% increase in all-cause mortality (hazard ratio, 1.46; 95% confidence interval: 1.17, 1.83), while those with poor CVH demonstrated a 101.0% increase (2.01; 1.54, 2.62). For CVD mortality, individuals with intermediate CVH experienced a 56.0% increase (1.56; 1.02, 2.39), and those with poor CVH demonstrated a 143.0% increase (2.43; 1.51, 3.91). Linear trends were noted for the associations of CVH with both all-cause mortality (P for trend <0.001) and CVD mortality (P for trend = 0.02). CONCLUSIONS: Lower CVH levels were associated with higher all-cause and CVD mortality in individuals with CKD, which highlights the importance of maintaining good CVH in CKD patients.

Zero-shot learning enables instant denoising and super-resolution in optical fluorescence microscopy.

Computational super-resolution methods, including conventional analytical algorithms and deep learning models, have substantially improved optical microscopy. Among them, supervised deep neural networks have demonstrated outstanding performance, however, demanding abundant high-quality training data, which are laborious and even impractical to acquire due to the high dynamics of living cells. Here, we develop zero-shot deconvolution networks (ZS-DeconvNet) that instantly enhance the resolution of microscope images by more than 1.5-fold over the diffraction limit with 10-fold lower fluorescence than ordinary super-resolution imaging conditions, in an unsupervised manner without the need for either ground truths or additional data acquisition. We demonstrate the versatile applicability of ZS-DeconvNet on multiple imaging modalities, including total internal reflection fluorescence microscopy, three-dimensional wide-field microscopy, confocal microscopy, two-photon microscopy, lattice light-sheet microscopy, and multimodal structured illumination microscopy, which enables multi-color, long-term, super-resolution 2D/3D imaging of subcellular bioprocesses from mitotic single cells to multicellular embryos of mouse and C. elegans.

The species and abundance of gut bacteria both positively impact Phortica okadai behavior.

BACKGROUND: Gut bacteria, which serve as essential modulators, exert a significant impact on insect physiology and behavior and have substantial application potential in pest management. The dynamics of gut bacteria and their impact on Phortica okadai behavior remain unclear. METHODS: In this study, the dynamics of gut bacteria at different developmental stages in P. okadai were analyzed using 16S ribosomal RNA (rRNA) gene sequencing, and the species and abundance of gut bacteria that affect host behavior were examined via behavioral experiments. RESULTS: A total of 19 phyla, 29 classes, 74 orders, 101 species, and 169 genera were identified. The results of the behavioral experiments indicated that the species Lactiplantibacillus argentoratensis, Acetobacter tropicalis, Leuconostoc citreum, and Levilactobacillus brevis effectively influenced the feeding preference of P. okadai, and the single-bacterium-seeded P. okadai exhibited feeding preferences distinct from those of the germ-free (GF) and wild-type P. okadai. CONCLUSIONS: The species and relative abundance of gut bacteria together positively impact P. okadai behavior. Lactiplantibacillus argentoratensis, as the most attractive bacteria to P. okadai, presents opportunities for novel pest control strategies targeting this vector and agricultural pest.

A fully autonomous robotic ultrasound system for thyroid scanning.

The current thyroid ultrasound relies heavily on the experience and skills of the sonographer and the expertise of the radiologist, and the process is physically and cognitively exhausting. In this paper, we report a fully autonomous robotic ultrasound system, which is able to scan thyroid regions without human assistance and identify malignant nod- ules. In this system, human skeleton point recognition, reinforcement learning, and force feedback are used to deal with the difficulties in locating thyroid targets. The orientation of the ultrasound probe is adjusted dynamically via Bayesian optimization. Experimental results on human participants demonstrated that this system can perform high-quality ultrasound scans, close to manual scans obtained by clinicians. Additionally, it has the potential to detect thyroid nodules and provide data on nodule characteristics for American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) calculation.

Thalamic Nucleus Reuniens Glutamatergic Neurons Mediate Colorectal Visceral Pain in Mice via 5-HT2B Receptors.

Irritable bowel syndrome (IBS) is a common functional bowel disorder characterized by abdominal pain and visceral hypersensitivity. Reducing visceral hypersensitivity is the key to effectively relieving abdominal pain in IBS. Increasing evidence has confirmed that the thalamic nucleus reuniens (Re) and 5-hydroxytryptamine (5-HT) neurotransmitter system play an important role in the development of colorectal visceral pain, whereas the exact mechanisms remain largely unclear. In this study, we found that high expression of the 5-HT2B receptors in the Re glutamatergic neurons promoted colorectal visceral pain. Specifically, we found that neonatal maternal deprivation (NMD) mice exhibited visceral hyperalgesia and enhanced spontaneous synaptic transmission in the Re brain region. Colorectal distension (CRD) stimulation induced a large amount of c-Fos expression in the Re brain region of NMD mice, predominantly in glutamatergic neurons. Furthermore, optogenetic manipulation of glutamatergic neuronal activity in the Re altered colorectal visceral pain responses in CON and NMD mice. In addition, we demonstrated that 5-HT2B receptor expression on the Re glutamatergic neurons was upregulated and ultimately promoted colorectal visceral pain in NMD mice. These findings suggest a critical role of the 5HT2B receptors on the Re glutamatergic neurons in the regulation of colorectal visceral pain.

FokI-RYdCas9 Mediates Nearly PAM-Less and High-Precise Gene Editing in Human Cells.

The demand for high-precision CRISPR/Cas9 systems in biomedicine is experiencing a notable upsurge. The editing system fdCas9 employs a dual-sgRNA strategy to enhance editing accuracy. However, the application of fdCas9 is constrained by the stringent requirement for two protospacer adjacent motifs (PAMs) of Cas9. Here, we devised an optimized editor, fRYdCas9, by merging FokI with the nearly PAM-less RYdCas9 variant, and two fRYdCas9 systems formed a dimer in a proper spacer length to accomplish DNA cleavage. In comparison to fdCas9, fRYdCas9 demonstrates a substantial increase in the number of editable genomic sites, approximately 330-fold, while maintaining a comparable level of editing efficiency. Through meticulous experimental validation, we determined that the optimal spacer length between two FokI guided by RYdCas9 is 16 base pairs. Moreover, fRYdCas9 exhibits a near PAM-less feature, along with no on-target motif preference via the library screening. Meanwhile, fRYdCas9 effectively addresses the potential risks of off-targets, as analyzed through whole genome sequencing (WGS). Mouse embryonic editing shows fRYdCas9 has robust editing capabilities. This study introduces a potentially beneficial alternative for accurate gene editing in therapeutic applications and fundamental research.

Divacancy and resonance level enables high thermoelectric performance in n-type SnSe polycrystals.

N-type polycrystalline SnSe is considered as a highly promising candidates for thermoelectric applications due to facile processing, machinability, and scalability. However, existing efforts do not enable a peak ZT value exceeding 2.0 in n-type polycrystalline SnSe. Here, we realized a significant ZT enhancement by leveraging the synergistic effects of divacancy defect and introducing resonance level into the conduction band. The resonance level and increased density of states resulting from tungsten boost the Seebeck coefficient. The combination of the enhanced electrical conductivity (achieved by increasing carrier concentration through WCl6 doping and Se vacancies) and large Seebeck coefficient lead to a high power factor. Microstructural analyses reveal that the co-existence of divacancy defects (Se vacancies and Sn vacancies) and endotaxial W- and Cl-rich nanoprecipitates scatter phonons effectively, resulting in ultralow lattice conductivity. Ultimately, a record-high peak ZT of 2.2 at 773 K is achieved in n-type SnSe0.92 + 0.03WCl6.

Enhancing Thermoelectric Performance of n-Type Bi2Te2.7Se0.3 through Incorporation of Amorphous Si3N4 Nanoparticles.

Bi2Te3-based thermoelectric (TE) materials are the state-of-the-art compounds for commercial applications near room temperature. Nevertheless, the application of the n-type Bi2Te2.7Se0.3 (BTS) is restricted by the comparatively low figure of merit (ZT) and intrinsic embrittlement. Here, we show that through dispersion of amorphous Si3N4 (a-Si3N4) nanoparticles both 14% increase in power factor (at 300 K) and 48% decrease in lattice thermal conductivity are simultaneously realized. The increased power factor comes from enhanced thermopower and reduced electrical resistivity while the reduced lattice thermal conductivity originates mainly from scattering of middle- and low-frequency phonons at the incorporated a-Si3N4 nanoparticles. As a result, a large ZTmax = 1.19 (at 373 K) and an average ZTave ∼ 1.12 (300-473 K) with better mechanical properties are achieved for the BTS/0.25 wt % Si3N4 sample. Present results demonstrate that the incorporation of a-Si3N4 is a promising way to improve TE performance.

Individual and joint associations of per- and polyfluoroalkyl substances (PFAS) with gallstone disease in adults: A cross-sectional study.

Disturbances in the enterohepatic circulation are important biological mechanisms for causing gallstones and also have important effects on the metabolism of Per- and polyfluoroalkyl substances (PFAS). Moreover, PFAS is associated with sex hormone disorder which is another important cause of gallstones. However, it remains unclear whether PFAS is associated with gallstones. In this study, we used logistic regression, restricted cubic spline (RCS), quantile g-computation (qg-comp), Bayesian kernel machine regression (BKMR), and subgroup analysis to assess the individual and joint associations of PFAS with gallstones and effect modifiers. We observed that the individual associations of perfluorodecanoic acid (PFDeA) (OR: 0.600, 95% CI: 0.444 to 0.811), perfluoroundecanoic acid (PFUA) (OR: 0.630, 95% CI: 0.453 to 0.877), n-perfluorooctane sulfonic acid (n-PFOS) (OR: 0.719, 95% CI: 0.571 to 0.906), and perfluoromethylheptane sulfonic acid isomers (Sm-PFOS) (OR: 0.768, 95% CI: 0.602 to 0.981) with gallstones were linearly negative. Qg-comp showed that the PFAS mixture (OR: 0.777, 95% CI: 0.514 to 1.175) was negatively associated with gallstones, but the difference was not statistically significant, and PFDeA had the highest negative association. Moreover, smoking modified the association of perfluorononanoic acid (PFNA) with gallstones. BKMR showed that PFDeA, PFNA, and PFUA had the highest groupPIP (groupPIP = 0.93); PFDeA (condPIP = 0.82), n-perfluorooctanoic acid (n-PFOA) (condPIP = 0.68), and n-PFOS (condPIP = 0.56) also had high condPIPs. Compared with the median level, the joint association of the PFAS mixture with gallstones showed a negative trend; when the PFAS mixture level was at the 70th percentile or higher, they were negatively associated with gallstones. Meanwhile, when other PFAS were fixed at the 25th, 50th, and 75th percentiles, PFDeA had negative associations with gallstones. Our evidence emphasizes that PFAS is negatively associated with gallstones, and more studies are needed in the future to definite the associations of PFAS with gallstones and explore the underlying biological mechanisms.

Function and mechanism exploring of icariin in schizophrenia through network pharmacology.

This study aims to explore the therapeutic effect and possible mechanisms of icariin in schizophrenia. SD rats were divided into five groups, a control group, a MK801-induced schizophrenia model group, and three icariin treatment groups, with twelve rats in each group. Morris water maze and open field were used to observe the spatial learning and memory ability of rats. Compared with the control group, rats in the MK801-induced model group showed an increase in stereotypic behavior score, distance of spontaneous activities, escape latency, malondialdehyde (MDA) content, and IL-6, IL-1ß, TNF-α expression, but a decrease in platform crossing times and superoxide dismutase (SOD) activity (P < 0.05). Furthermore, all the above changes of the model group were reversed after icariin treatment in a dose-dependent manner (P < 0.05). Network pharmacology found that icariin can exert anti-schizophrenic effects through some signaling pathways, such as relaxin, estrogen, and TNF signaling pathways. MAPK1, MAPK3, FOS, RELA, TNF, and JUN were the key targets of icariin on schizophrenia, and their expression was detected in animal models, which was consistent with the predicted results of network pharmacology. Icariin treatment may improve the spatial learning and memory ability of schizophrenic rats through TNF signaling pathway.

The effects of hyperbaric oxygen therapy on neuroprotection and recovery after brain resuscitation.

OBJECTIVE: Analyze the impact of hyperbaric oxygen therapy on neuroprotection and recovery post severe traumatic brain injury (sTBI) resuscitation. METHODS: Retrospective analysis of clinical data from 83 sTBI patients admitted between January 2022 to January 2024. Patients were divided into control (n = 41) and observation (n = 42) groups based on treatment received. Control received standard therapy, while the observation group received hyperbaric oxygen therapy. Effects on clinical outcomes, neuroinjury markers (S100ß, GFAP, UCH-L1, NSE), neurotrophic factors (NGF, BDNF), neurological function indicators (NIHSS, CSS), and adverse reactions were compared. RESULTS: The observation group showed a higher total effective rate (80.95%) compared to control (60.98%) (p < 0.05). Neuroinjury markers decreased post-treatment in both groups, with the observation group lower (p < 0.05). NGF and BDNF levels increased post-treatment in both groups, with the observation group higher (p < 0.05). NIHSS and CSS scores decreased post-treatment in both groups, with the observation group lower (p < 0.05). No significant difference in adverse reactions between groups (p > 0.05). CONCLUSION: Hyperbaric oxygen therapy effectively treats sTBI by improving brain resuscitation success, reducing neuroinjury factors, enhancing neurotrophic factors, and promoting neurological function recovery, without increasing adverse reaction risk.

Matrine reverses the resistance of Haemophilus parasuis to cefaclor by inhibiting the mutations in penicillin-binding protein genes (ftsI and mrcA).

Introduction: Matrine (MT) is a potential resistance reversal agent. However, it remains unclear whether MT can reverse the resistance of Haemophilus parasuis (H. parasuis) to ß-lactams, and, if so, by what mechanism MT works. Methods: We screened one cefaclor (CEC)-resistant strain (clinical strain C7) from eight clinical (H. parasuis) strains and determined the underlying resistance mechanism. Then, we investigated the reversal effect of MTon the resistance of this strain to CEC. Results and Discussion: The production of ß-lactamase, overexpression of AcrAB-TolC system, and formation of biofilm might not be responsible for the resistance of clinical strain C7 to CEC. Fourteen mutation sites were found in four PBP genes (ftsI, pbp1B, mrcA, and prcS) of clinical strain C7, among which the mutation sites located in ftsI (Y103D and L517R) and mrcA (A639V) genes triggered the resistance to CEC. The minimum inhibitory concentration (MIC) of CEC against clinical strain C7 was reduced by two to eight folds after MT treatment, accompanied by the significant down-regulated expression of mutated ftsI and mrcA genes. Based on such results, we believed that MT could reverse the resistance of H. parasuis to CEC by inhibiting the mutations in ftsI and mrcA genes. Our research would provide useful information for restoring the antimicrobial activity of ß-lactams and improving the therapeutic efficacy of Glässer's disease.

Comparative quantitative analysis of optical coherence tomography angiography in varied morphologies of macular neovascularization following intravitreal conbercept and ranibizumab treatments for neovascular age­related macular degeneration.

The present study aimed to examine the optical coherence tomography angiography (OCTA) parameters associated with macular neovascularization (MNV) in patients diagnosed with neovascular age-related macular degeneration (nAMD) and treated with either intravitreal conbercept (IVC) or ranibizumab (IVR). It enrolled 39 nAMD patients presenting with MNV, including 23 in the IVC group and 16 in the IVR group. All participants were treatment-naïve with intravitreal therapy and they underwent treatment following a '3+PRN' regimen. The MNV patterns identified through OCTA were categorized as Medusa, tangled, seafan and other variations. Key outcome measures encompassed best-corrected visual acuity (BCVA), MNV vascular area (MNV-VA), MNV vascular density (MNV-VD) ratio and central macular thickness (CMT). In the present study, 44 eyes were included, with 28 eyes undergoing treatment with IVC and 18 eyes with IVR. On day 90, there was a statistically significant improvement in mean BCVA from baseline among all patients treated with IVC (P=0.002). Notably, improved outcomes were observed in those with the 'tangled' pattern compared with the other three patterns (P=0.007). CMT exhibited a significant decrease from baseline (P=0.007), with consistent improvement observed across all four patterns (P=0.052) on day 90. The mean MNV-VA decreased in all patients, reaching statistical significance for the Medusa pattern (P=0.008), although the improvement in visual acuity was deemed unsatisfactory. Patients with the seafan pattern treated with IVR improved significantly in BCVA (P=0.042). The mean CMT significantly improved from baseline (P=0.001), consistent across the four patterns (P=0.114). Significant improvements were noted in the mean MNV-VA for the seafan pattern and in the mean MNV-VD ratio for the other patterns. The two regimens had no significant differences regarding BCVA, CMT, and MNV parameters. Conbercept emerged as a viable treatment option for patients presenting with tangled MNV patterns. On the other hand, ranibizumab might be considered an effective intervention for individuals with seafan MNV patterns. Notably, the Medusa MNV pattern was associated with a morphologic configuration indicative of a poor prognosis.

Achieving High Isotropic Figure of Merit in Cd and in Codoped Polycrystalline SnSe.

Here, we combined Cd and In codoping with a simple hydrothermal synthesis method to prepare SnSe powders composed of nanorod-like flowers. After spark plasma sintering, its internal grains inherited well the morphological features of the precursor, and the multiscale microstructure included nanorod-shaped grains, high-density dislocations, and stacking faults, as well as abundant nanoprecipitates, resulting in an ultralow thermal conductivity of 0.15 W m-1 K-1 for the synthesized material. At the same time, Cd and In synergistically regulated the electrical conductivity and Seebeck coefficient of SnSe, leading to an enhanced power factor. Among them, Sn0.94Cd0.03In0.03Se achieved a peak ZT of 1.50 parallel to the pressing direction, representing an 87.5% improvement compared with pure SnSe. Notably, the material possesses isotropic ZT values parallel and perpendicular to the pressing direction, overcoming the characteristic anisotropy in thermal performance observed in previous polycrystalline SnSe-based materials. Our results provide a new strategy for optimizing the performance of thermoelectric materials through structural engineering.

Comprehensive analysis of the protein phosphatase 2A regulatory subunit B56ε in pan-cancer and its role and mechanism in hepatocellular carcinoma.

BACKGROUND: B56ε is a regulatory subunit of the serine/threonine protein phosphatase 2A, which is abnormally expressed in tumors and regulates various tumor cell functions. At present, the application of B56ε in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear. AIM: To analyze B56ε in pan-cancer, and explore its role and mechanism in HCC. METHODS: The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Profiling Interactive Analysis, and Tumor Immune Estimation Resource databases were used to analyze B56ε expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56ε expression levels and drug sensitivity, immunotherapy, immune checkpoints, and human leukocyte antigen (HLA)-related genes were further analyzed. Gene Set Enrichment Analysis (GSEA) was performed to reveal the role of B56ε in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56ε interference on the malignant behavior of HCC cells. RESULTS: In most tumors, B56ε expression was upregulated, and high B56ε expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all P < 0.05). B56ε expression levels were correlated with a variety of immune cells, such as T helper 17 cells, B cells, and macrophages. There was a positive correlation between B56ε expression levels with immune checkpoint genes and HLA-related genes (all P < 0.05). The expression of B56ε was negatively correlated with the sensitivity of most chemotherapy drugs, but a small number showed a positive correlation (all P < 0.05). GSEA analysis showed that B56ε expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56ε expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells. CONCLUSION: B56ε is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56ε plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC.

Systemic immune index predicts tumor-infiltrating lymphocyte intensity and immunotherapy response in small cell lung cancer.

Background: Despite recent progresses in immune checkpoint blockade (ICB) in small-cell lung cancer (SCLC), a lack of understanding regarding the systemic tumor immune environment (STIE) and local tumor immune microenvironment (TIME) makes it difficult to accurately predict clinical outcomes and identify potential beneficiaries from ICB therapy. Methods: We enrolled 191 patients with stage I-III SCLC and comprehensively evaluated the prognostic role of STIE by several quantitative measurements, and further integrate it with a local immune score system (LISS) established by eXtreme Gradient Boosting (XGBoost) machine learning algorithm. We also test the value of STIE in beneficiary selection in our independent advanced SCLC cohort receiving programmed cell death 1 ligand 1 (PD-L1) blockade therapy. Results: Among several systemic immune markers, the STIE as assessed by prognostic nutritional index (PNI) was correlated with disease-free survival (DFS) and overall survival (OS), and remained as an independent prognostic factor for SCLC patients [hazard ratio (HR): 0.473, 95% confidence interval (CI): 0.241-0.929, P=0.030]. Higher PNI score was closely associated with inflamed SCLC molecular subtype and local tumor-infiltrating lymphocytes (TILs). We further constructed a LISS which combined top three important local immune biomarkers (CD8+ T-cell count, PD-L1 expression on CD8+ T-cell and CD4+ T-cell count) and integrated it with the PNI score. The final integrated immune risk system was an independent prognostic factor and achieved better predictive performance than Tumor Node Metastasis (TNM) stages and single immune biomarker. Furthermore, PNI-high extensive-stage SCLC patients achieved better clinical response and longer progression-free survival (PFS) (11.8 vs. 5.9 months, P=0.012) from PD-L1 blockade therapy. Conclusions: This study provides a method to investigate the prognostic value of overall immune status by combining the PNI with local immune biomarkers in SCLC. The promising clinical application of PNI in efficacy prediction and beneficiary selection for SCLC immunotherapy is also highlighted.

Study on Interpretation Method of Multistage Fracture Tracer Flowback Curve in Tight Oil Reservoirs.

Multistage fracturing is widely used in the development of tight oil reservoirs, and the fine description of postfracturing fracture networks is a challenge in tight oil reservoir development. Based on the formation mechanism of dual-wing fractures and the principles of tracer flowback, a mathematical model for tracer concentration in dual-wing fractures is established by considering the convective diffusion of the tracer within the fractures. An interpretation method for tracer flowback curves, utilizing a combination of Gaussian fitting and theoretical equation inversion, is developed to provide a detailed description of fracture parameters such as fracture half-length, fracture width, and fracture conductivity in the postfracturing fracture network. This method can be rapidly applied in field practices. Application examples demonstrate that the relative errors between the calculated cumulative oil and water production using this method and the actual data are less than 5%, validating the accuracy and applicability of the established mathematical model for tracer flowback and the interpretation method for tracer concentration curves in addressing practical problems.

Boosting Thermoelectric Performance of PbBi2 Te4 via Reduced Carrier Scattering and Intensified Phonon Scattering.

Materials with low intrinsic lattice thermal conductivity are crucial in the pursuit of high-performance thermoelectric (TE) materials. Here, the TE properties of PbBi2 Te4-x Sex (0 ≤ x ≤ 0.6) samples are systematically investigated for the first time. Doping with Se in PbBi2 Te4 can simultaneously reduce carrier concentration and increase carrier mobility. The Seebeck coefficient is significantly increased by doping with Se, based on the density functional theory calculation, it is shown to be due to the increased bandgap and electronic density of states. In addition, the lattice strain is enhanced due to the difference in the size of Se and Te atoms, and the multidimensional defects formed by Se doping, such as vacancies, dislocations, and grain boundaries, enhance the phonon scattering and reduce the lattice thermal conductivity by about 37%. Finally, by using Se doping to reduce carrier concentration and thermal conductivity, a large ZTmax = 0.56 (at 574K) is achieved for PbBi2 Te3.5 Se0.5 , which is around 64% larger than those of the PbBi2 Te4 pristine sample. This work not only demonstrates that PbBi2 Te4 is a potential medium temperature thermoelectric material, but also provides a reference for enhancing thermoelectric properties through defect and energy band engineering.

Predicting locus-specific DNA methylation levels in cancer and paracancer tissues.

Aim: To predict base-resolution DNA methylation in cancerous and paracancerous tissues. Material & methods: We collected six cancer DNA methylation datasets from The Cancer Genome Atlas and five cancer datasets from Gene Expression Omnibus and established machine learning models using paired cancerous and paracancerous tissues. Tenfold cross-validation and independent validation were performed to demonstrate the effectiveness of the proposed method. Results: The developed cross-tissue prediction models can substantially increase the accuracy at more than 68% of CpG sites and contribute to enhancing the statistical power of differential methylation analyses. An XGBoost model leveraging multiple correlating CpGs may elevate the prediction accuracy. Conclusion: This study provides a powerful tool for DNA methylation analysis and has the potential to gain new insights into cancer research from epigenetics.

Exploration of hypoglycemic peptides from porcine collagen based on network pharmacology and molecular docking.

In recent years, the extraction of hypoglycemic peptides from food proteins has gained increasing attention. Neuropeptides, hormone peptides, antimicrobial peptides, immune peptides, antioxidant peptides, hypoglycemic peptides and antihypertensive peptides have become research hotspots. In this study, bioinformatic methods were used to screen and predict the properties of pig collagen-derived hypoglycemic peptides, and their inhibitory effects on α-glucosidase were determined in vitro. Two peptides (RL and NWYR) were found to exhibit good water solubility, adequate ADMET (absorption, distribution, metabolism, elimination, and toxicity) properties, potentially high biological activity, and non-toxic. After synthesizing these peptides, NWYR showed the best inhibitory effect on α-glucosidase with IC50 = 0.200±0.040 mg/mL, and it can regulate a variety of biological processes, play a variety of molecular functions in different cellular components, and play a hypoglycemic role by participating in diabetic cardiomyopathy and IL-17 signaling pathway. Molecular docking results showed that NWYR had the best binding effect with the core target DPP4 (4n8d), with binding energy of -8.8 kcal/mol. NWYR mainly bonded with the target protein through hydrogen bonding, and bound with various amino acid residues such as Asp-729, Gln-731, Leu-765, etc., thus affecting the role of the target in each pathway. It is the best core target for adjuvant treatment of T2DM. In short, NWYR has the potential to reduce type 2 diabetes, providing a basis for further research or food applications as well as improved utilization of pig by-products. However, in subsequent studies, it is necessary to further verify the hypoglycemic ability of porcine collagen active peptide (NWYR), and explore the hypoglycemic mechanism of NWYR from multiple perspectives such as key target genes, protein expression levels and differences in metabolites in animal models of hyperglycemia, which will provide further theoretical support for its improvement in the treatment of T2DM.