Network pharmacology-based exploration of molecular mechanisms underlying therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure with spleen Qi deficiency syndrome.

BACKGROUND: Chronic heart failure is a complex clinical syndrome. The Chinese herbal compound preparation Jianpi Huatan Quyu recipe has been used to treat chronic heart failure; however, the underlying molecular mechanism is still not clear. AIM: To identify the effective active ingredients of Jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart failure. METHODS: The effective active ingredients of eight herbs composing Jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The target genes of chronic heart failure were searched in the Genecards database. The target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drug-disease targets, which were then used to construct a key chemical component-target network using Cytoscape 3.7.2 software. The protein-protein interaction network was constructed using the String database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape database. Finally, our previously published relevant articles were searched to verify the results obtained via network pharmacology. RESULTS: A total of 227 effective active ingredients for Jianpi Huatan Quyu recipe were identified, of which quercetin, kaempferol, 7-methoxy-2-methyl isoflavone, formononetin, and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3, MAPK3, AKT1, JUN, MAPK1, TP53, TNF, HSP90AA1, p65, MAPK8, MAPK14, IL6, EGFR, EDN1, FOS, and other proteins. The pathways identified by KEGG enrichment analysis include pathways in cancer, IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, cAMP signaling pathway, NF-kappaB signaling pathway, AMPK signaling pathway, etc. Previous studies on Jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α, IL-6, MAPK, cAMP, and AMPK pathways to affect the mitochondrial structure of myocardial cells, oxidative stress, and energy metabolism, thus achieving the therapeutic effects on chronic heart failure. CONCLUSION: The Chinese medicine compound preparation Jianpi Huatan Quyu recipe exerts therapeutic effects on chronic heart failure possibly by influencing the mitochondrial structure of cardiomyocytes, oxidative stress, energy metabolism, and other processes. Future studies are warranted to investigate the role of the IL-17 signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and other pathways in mediating the therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure.

Polysulfone Membranes Decorated with Fe-Mn binary oxide nanoparticles and Polydopamine for Enhanced Arsenate/Arsenite Adsorptive Removal.

Arsenic contamination of water is a global environmental concern, and membrane technology combined with nanotechnology contributes to more efficient removal of arsenic. In this study, Fe-Mn oxide (FM), Polydopamine (PDA), and PDA-modified FM (PFM) were incorporated into polysulfone (PSF) to prepare adsorption membranes (PFMP) for arsenic removal. The prepared nanoparticles and membranes were characterized using TEM, SEM, FTIR, TGA, contact angle, and pure water flux. The introduction of particles enhanced the hydrophilicity of the membranes and significantly enhanced the pure water flux of the membranes. Adsorption experiments indicated that the PFMP membrane exhibited the best arsenic removal performance, with maximum adsorption capacities for As(III) and As(V) were 11.57 mg/g and 12.39 mg/g, respectively. The Langmuir model fitted the adsorption isotherms well, and the kinetics followed the pseudo-second-order model. The filtration experiment revealed that the PFMP membrane was capable of reducing As(III) solution (915 L/m2) and As(V) solution (1075 L/m2) from a concentration of 100 µg/L to the safe limit of As (＜10 µg/L). The As-loaded membrane was regenerated using NaOH solution (pH=11), and the filtration experiment was repeated. FTIR and XPS demonstrated that the mechanism of the reaction between the membrane and arsenic was ligand exchange, where the arsenic ions were bonded to the oxygen ions to form Mn-O-As and Fe-O-As.

Modulation of the pharmacokinetics of soluble ACE2 decoy receptors through glycosylation.

The Spike of SARS-CoV-2 recognizes a transmembrane protease, angiotensin-converting enzyme 2 (ACE2), on host cells to initiate infection. Soluble derivatives of ACE2, in which Spike affinity is enhanced and the protein is fused to Fc of an immunoglobulin, are potent decoy receptors that reduce disease in animal models of COVID-19. Mutations were introduced into an ACE2 decoy receptor, including adding custom N-glycosylation sites and a cavity-filling substitution together with Fc modifications, which increased the decoy's catalytic activity and provided small to moderate enhancements of pharmacokinetics following intravenous and subcutaneous administration in humanized FcRn mice. Most prominently, sialylation of native glycans increases exposures by orders of magnitude, and the optimized decoy is therapeutically efficacious in a mouse COVID-19 model. Ultimately, an engineered and highly sialylated decoy receptor produced using methods suitable for manufacture of representative drug substance has high exposure with a 5- to 9-day half-life. Finally, peptide epitopes at mutated sites in the decoys generally have low binding to common HLA class II alleles and the predicted immunogenicity risk is low. Overall, glycosylation is a critical molecular attribute of ACE2 decoy receptors and modifications that combine tighter blocking of Spike with enhanced pharmacokinetics elevate this class of molecules as viable drug candidates.

SET8 inhibition preserves PTEN to attenuate kidney cell apoptosis in cisplatin nephrotoxicity.

The aberrant expression of SET8, a histone methyltransferase that mediates H4 lysine 20 mono-methylation (H4K20me1), is implicated in the pathogenesis of various tumors, however, its role in acute kidney injury (AKI) is unknown. Here we showed that SET8 and H4K20me1 were upregulated in the murine kidney with AKI induced by cisplatin, along with increased renal tubular cell injury and apoptosis and decreased expression of E-cadherin and Phosphatase and Tensin Homolog (PTEN). Suppression of SET8 by UNC0379 improved renal function, attenuated tubule damage, and restored expression of PTEN, but not E-cadherin. UNC0379 was also effective in lessening cisplatin-induced DNA damage response (DDR) as indicated by reduced expression of γ-H2AX, p53, p21, and alleviating cisplatin-impaired autophagy as shown by retained expression of Atg5, Beclin-1, and CHMP2A and enhanced levels of LC3-II in the kidney. Consistently, inhibition of SET8 with either UNC0379 or siRNA mitigated apoptosis and DDR, and restored autophagy, along with PTEN preservation in cultured renal proximal tubular epithelial cell (TKPTs) exposed to cisplatin. Further studies showed that inhibition of PTEN with Bpv or siRNA potentiated cisplatin-induced apoptosis, DDR, and hindered autophagy, and conversely, alleviated by overexpression of PTEN in TKPTs. Finally, blocking PTEN largely abolished the inhibitory effect of UNC0379 on apoptosis. Taken together, these results suggest that SET8 inhibition protects against cisplatin-induced AKI and renal cell apoptosis through a mechanism associated with the preservation of PTEN, which in turn inhibits DDR and restores autophagy.

Key genomes, transcriptomes, proteins, and metabolic factors involved in the detoxification/tolerance of TNT and its intermediates by bacteria in anaerobic/aerobic environments.

Novel microbial strains capable of efficient degradation of TNT and typical intermediates (2-ADNT and 4-ADNT) in aerobic/anaerobic environment were screened and isolated from ammunition-contaminated sites. The key genomes, transcriptomes, proteins, and metabolic factors for microbial detoxification/tolerance to pollutants in anaerobic and aerobic environments were analyzed for the first time. The bacterial genome, which is rich in metabolism and environmental information-processing functional genes, provides transcriptional and translational-related proteins for detoxifying/tolerating pollutants. At the transcriptional level, bacteria significantly expressed genes related to inositol phosphate metabolism for regulating membrane transport, maintaining the cytoskeleton, and signal transduction. At the protein level, genes involved in antioxidation, fat metabolism, sugar synthesis/degradation, and pyruvate metabolism were significantly expressed. At the metabolic level, riboflavin metabolism, which regulates membrane integrity, protects against oxidative stress, and maintains the sugar-protein-fat balance, showed significant responses. Bacteria simultaneously regulate amino acid metabolism, carbohydrate metabolism, and N/P/S cycles to maintain homeostatic cellular energy supplies. The key pathway for pollutant degradation in bacteria is nitrotoluene degradation. The molecular mechanism of bacterial tolerance to pollutants involves the regulation of oxidative phosphorylation and basic cycle pathways to maintain gene transcription, protein translation, and metabolic cycles.

Prediction of laser printers and cartridges based on three-dimensional profiles via discrimination analysis.

Printer source prediction is an important task when examining questioned documents. While some research has provided methods to predict the source printer of documents, with the advent of compatible consumables, printer prediction could become more complex and difficult. Predicting the source printer after replacing cartridges and identifying the source of printer cartridges are unresolved issues that are rarely addressed in current research. Herein, we introduce a novel technique to predict the manufacturer, model, and cartridges of laser printers (i.e., compatible, and original cartridges) used to produce a given document. Document samples produced using eight laser printers and 247 cartridges were collected to establish a dataset. Common manufacturers included HP, Canon, Lenovo, and Epson. After obtaining white-light images and three-dimensional profile images of printed characters, a morphological analysis was conducted by questioned document examiners (QDEs) using microscopy. Microscopic image features across a series of images were also extracted and analyzed using algorithms. Then, six high-dimensional reduction algorithms were used to obtain between- and within-printer variations as well as between- and within-cartridge variations. Finally, we conducted principal component analysis (PCA) and discriminant analysis. For 40 % of the samples, mixed discrimination analysis (MDA) and fixed discrimination analysis (FDA) were employed to predict the manufacturer, model and cartridge of laser printers used to produce the questioned printed document; the remaining 60 % samples comprised the training dataset. In the prediction of manufacturer, model and cartridge, our method achieved mean accuracies of 95.5 %, 97.5 %, and 90.2 %, respectively. Hence, this technique could reasonably aid in predicting the manufacturer, model, and cartridge of a laser printer, even if different cartridges are loaded into printers.

Sulfur occupancy-induced construction of ant-nest-like NiMo/CF(N) electrode for highly efficient hydrogen evolution.

The microstructure of the electrocatalyst plays a critical role in the reaction efficiency and stability during electrochemical water splitting. Designing an efficient and stable electrocatalyst, further clarifying the synthesis mechanism, is still an important problem to be solved urgently. Inspired by the copper pyrometallurgy theory, an exceptionally active NiMo/CF(N) electrode, consisting of an ant-nest-like copper foam substrate (defined as CF(N)) and deposited NiMo layer, was fabricated for the alkaline hydrogen evolution reaction (HER). Our findings expounded the structure construction mechanism and highlighted the pivotal role of the spatial occupancy of sulfur atoms in the construction of the ant-nest-like structure. The NiMo/CF(N) composite, characterized by channels with a 2 µm diameter, showcases strong electronic interactions, increased catalytic active sites, enhanced electron/ion transport, and facilitated gas release during HER. Remarkably, NiMo/CF(N) demonstrates ultralow overpotentials of 21 mV to deliver a current density of 10 mA cm-2 in 1 M KOH. This electrode also exhibits outstanding durability, maintaining a current density of 200 mA cm-2 for 110 h, attributed to the chemical and structural integrity of its catalytic surface and the excellent mechanical properties of the electrode. This work advances the fundamental understanding of constructing micro/nano-structured electrocatalysts for highly efficient water splitting.

Patient-reported outcomes in lung cancer surgery: A narrative review.

Lung cancer is a leading cause of cancer-related mortality worldwide, profoundly affecting patients' quality of life. Patient-reported outcomes (PROs) provide essential insights from the patients' perspective, a crucial aspect often overlooked by traditional clinical outcomes. This review synthesizes research on the role of PROs in lung cancer surgery to enhance patient care and outcomes. We conducted a comprehensive literature search across PubMed, Scopus, and Web of Science up to March 2024, using terms such as "lung cancer," "Patient Reported Outcome," "lobectomy," "segmentectomy," and "lung surgery." The criteria included original studies on lung cancer patients who underwent surgical treatment and reported on PROs. After screening and removing duplicates, reviews, non-English articles, and irrelevant studies, 36 research articles were selected, supported by an additional 53 publications, totaling 89 references. The findings highlight the utility of PROs in assessing post-surgical outcomes, informing clinical decisions, and facilitating patient-centered care. However, challenges in standardization, patient burden, and integration into clinical workflows remain, underscoring the need for further research and methodological refinement. PROs are indispensable for understanding the quality-of-life post-surgery and enhancing communication and decision-making in clinical practice. Their integration into routine care is vital for a holistic approach to lung cancer treatment, promising significant improvements in patient outcomes and quality of care.

Lignin nanoparticles formation by multiscale structure control to regulate morphology and their adsorption, nucleation, and growth on chitin nanofibers.

The lignin nanoparticles (LNPs) synthesis relies on lignin polymers with heterogeneous molecules and properties, which impose significant limitations on the preparation and property regulation. The multiscale structure of lignin from monomers to oligomers, provides a potential pathway for precise regulation of its physical and chemical properties. The study addresses this challenge by employing coniferyl alcohol and sinapyl alcohol as monomers and separately utilizing the Zulaufverfaren (ZL) and Zutropfverfaren (ZT) methods to synthesize different types of lignin dehydrogenation polymers (DHPs) including guaiacyl (G)-ZL-DHP, G-ZT-DHP, syringyl (S)-ZL-DHP, and S-ZT-DHP. The investigation highlights the chemical bonds as essential components of lignin primary structure. Additionally, the secondary structure is influenced by branched and linear molecular structures. G unit provides some branching points, which are utilized and amplified in the ZL process of DHPs synthesis. The branched DHPs aggregate at the edge and form rod-like LNPs. While linear DHPs aggregate around the center, presenting polygonal LNPs. The study identifies that the branched LNPs, characterized by more surface charges and lower steric hindrance, can form a stable complex with chitin nanofibers. Emulsions with varying oil-to-water ratios were subsequently prepared, opening a new window for the application of LNPs in fields such as food and cosmetics.

Variational Discriminative Stacked Auto-Encoder: Feature Representation Using a Prelearned Discriminator, and Its Application to Industrial Process Monitoring.

In deep-learning-based process monitoring, obtaining an effective feature representation is a critical step in constructing a reliable deep-learning monitoring model. Conventional deep-learning methods like stacked auto-encoders (SAEs) capture feature representation by minimizing the data reconstruction errors, which lack the expression of essential information and ultimately lead to degradation of the monitoring performance. To solve this problem, variational discriminative SAE (VDSAE) is proposed in this article. First, a variational generative discriminative structure is designed to obtain a reliable prelearned discriminator. Based on this new variational discriminator, the authenticity of the reconstructed data is evaluated as an important criterion for feature learning. Then, an SAE incorporating the prelearned discriminator is trained by both minimizing the reconstruction error and maximizing the data authenticity. In this way, the prelearned discriminator makes the network effectively capture the essential expression of the reconstructed data. The proposed approach enables SAE to learn a better feature representation owing to the excellent reconstruction performance. Finally, the feature representation and fault detection performance of VDSAE are verified in two cases. The results show that the average fault detection rates (FDRs) of the multiphase flow facility and the waste-water treatment process (WWTP) can be improved to 72% and 97%, respectively, compared with the other fault detection methods.

Luminescence performance and antioxidant properties of selenium carbon dots prepared from selenium-hyperaccumulating plants.

Heteroatom doping has become an important method to enhance the performance of traditional carbon dots in modern times. Selenium (Se) is a nonmetallic trace element with excellent redox properties and is therefore essential for health. Previous studies have mainly used pure chemicals as selenium sources to prepare selenium-doped carbon dots (Se-CDs), but the precursor pure chemicals have the disadvantages of being expensive, difficult to obtain, toxic, and having low fluorescence yields of the synthesised Se-CDs. Fortunately, our team achieved successful synthesis of selenium carbon dots, exhibiting excellent luminescence and biocompatibility through a one-step hydrothermal method using selenium-enriched natural plant Cardamine, as an alternative to selenium chemicals. This approach aims to address the limitations and high costs associated with Se-CDs precursors. Electron spin resonance spectroscopy (ESR) and cellular antioxidant tests have confirmed the protective ability of Se-CDs against oxidative damage induced by excessive reactive oxygen species (ROS). A new concept and method for synthesizing selenium carbon dots on the basis of biomass, a rationale for the antioxidant effects on human health, and a wide range of development and application possibilities were offered in this work.

Enhancing diagnostic precision in EBV-related HLH: a multifaceted approach using 18F-FDG PET/CT and nomogram integration.

BACKGROUND: The hyperinflammatory condition and lymphoproliferation due to Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) affect the detection of lymphomas by 18F-FDG PET/CT. We aimed to improve the diagnostic capabilities of 18F-FDG PET/CT by combining laboratory parameters. METHODS: This retrospective study involved 46 patients diagnosed with EBV-positive HLH, who underwent 18F-FDG PET/CT before beginning chemotherapy within a 4-year timeframe. These patients were categorized into two groups: EBV-associated HLH (EBV-HLH) (n = 31) and EBV-positive lymphoma-associated HLH (EBV + LA-HLH) (n = 15). We employed multivariable logistic regression and regression tree analysis to develop diagnostic models and assessed their efficacy in diagnosis and prognosis. RESULTS: A nomogram combining the SUVmax ratio, copies of plasma EBV-DNA, and IFN-γ reached 100% sensitivity and 81.8% specificity, with an AUC of 0.926 (95%CI, 0.779-0.988). Importantly, this nomogram also demonstrated predictive power for mortality in EBV-HLH patients, with a hazard ratio of 4.2 (95%CI, 1.1-16.5). The high-risk EBV-HLH patients identified by the nomogram had a similarly unfavorable prognosis as patients with lymphoma. CONCLUSIONS: The study found that while 18F-FDG PET/CT alone has limitations in differentiating between lymphoma and EBV-HLH in patients with active EBV infection, the integration of a nomogram significantly improves the diagnostic accuracy and also exhibits a strong association with prognostic outcomes.

α7-nAChR/P300/NLRP3-regulated pyroptosis mediated poor articular cartilage quality induced by prenatal nicotine exposure in female offspring rats.

Nicotine is developmentally toxic. Prenatal nicotine exposure (PNE) affects the development of multiple fetal organs and causes susceptibility to a variety of diseases in offspring. In this study, we aimed to investigate the effect of PNE on cartilage development and osteoarthritis susceptibility in female offspring rats. Wistar rats were orally gavaged with nicotine on days 9-20 of pregnancy. The articular cartilage was obtained at gestational day (GD) 20 and postnatal week (PW) 24, respectively. Further, the effect of nicotine on chondrogenic differentiation was explored by the chondrogenic differentiation model in human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs). The PNE group showed significantly shallower Safranin O staining and lower Collagen 2a1 content of articular cartilage in female offspring rats. Further, we found that PNE activated pyroptosis in the articular cartilage at GD20 and PW24. In vitro experiments revealed that nicotine inhibited chondrogenic differentiation and activated pyroptosis. After interfering with nod-like receptors3 (NLRP3) expression by SiRNA, it was found that pyroptosis mediated the chondrogenic differentiation inhibition of WJ-MSCs induced by nicotine. In addition, we found that α7-nAChR antagonist α-BTX reversed nicotine-induced NLRP3 and P300 high expression. And, P300 SiRNA reversed the increase of NLRP3 mRNA expression and histone acetylation level in its promoter region induced by nicotine. In conclusion, PNE caused chondrodysplasia and poor articular cartilage quality in female offspring rats. PNE increased the histone acetylation level of NLRP3 promoter region by α7-nAChR/P300, which resulting in the high expression of NLRP3. Further, NLRP3 mediated the inhibition of chondrogenic differentiation by activating pyroptosis.

Higher immune cell radiation dose is correlated with poor tumor control and survival in patients with non-small cell lung cancer receiving postoperative radiotherapy.

INTRODUCTION: The estimated dose of radiation to immune cells (EDRIC) has been shown to correlate with the overall survival (OS) of patients who receive definitive thoracic radiotherapy. However, the planning target volume (PTV) may be a confounding factor. We assessed the prognostic value of EDRIC for non-small cell lung cancer (NSCLC) in patients who underwent postoperative radiotherapy (PORT) with homogeneous PTV. METHODS: Patients with NSCLC who underwent PORT between 2004 and 2019 were included. EDRIC was computed as a function of the number of radiation fractions and mean doses to the lungs, heart, and remaining body. The correlations between EDRIC and OS, disease-free survival (DFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed using univariate and multivariate Cox models. Kaplan-Meier analysis was performed to assess the survival difference between low- and high-EDRIC groups. RESULTS: In total, 345 patients were analyzed. The mean EDRIC was 6.26 Gy. Multivariate analysis showed that higher EDRIC was associated with worse outcomes in terms of OS (hazard ratio [HR] 1.207, P = .007), DFS (HR 1.129, P = .015), LRFS (HR 1.211, P = .002), and DMFS (HR 1.131, P = .057). In the low- and high-EDRIC groups, the 3-year OS was 81.2% and 74.0%, DFS 39.8% and 35.0%, LRFS 70.4% and 60.5%, and DMFS 73.9% and 63.1%, respectively. CONCLUSIONS: EDRIC is an independent prognostic factor for survival in patients with NSCLC undergoing PORT. Higher doses of radiation to the immune system are associated with tumor progression and poor survival. Organs at risk for the immune system should be considered during radiotherapy planning.

Immunosuppression and phenotypic plasticity in an atlas of human hepatocholangiocarcinoma.

Background: Hepatocholangiocarcinoma (H-ChC) has the clinicopathological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) and is a more aggressive subtype of primary hepatic carcinoma than HCC or iCCA. Methods: We sequenced 91,112 single-cell transcriptomes from 16 human samples to elucidate the molecular mechanisms underlying the coexistence of HCC and iCCA components in H-ChC. Results: We observed two molecular subtypes of H-ChC at the whole-transcriptome level (CHP and CIP), where a metabolically active tumour cell subpopulation enriched in CHP was characterized by a cellular pre-differentiation property. To define the heterogeneity of tumours and their associated microenvironments, we observe greater tumour diversity in H-ChC than HCC and iCCA. H-ChC exhibits weaker immune cell infiltration and greater CD8+ exhausted T cell (Tex) dysfunction than HCC and iCCA. Then we defined two broad cell states of 6,852 CD8+ Tex cells: GZMK+ CD8+ Tex cells and terminal CD8+ Tex cells. GZMK+ CD8+ Tex cells exhibited higher infiltration of after treatment in H-ChC, the effector scores and expression of the immune checkpoints of them greatly increased after immunotherapy, which indicated that H-ChC might be more sensitive than HCC or iCCA to immunotherapy. Conclusions: In this paper, H-ChC was explored, hoping to contribute to the study of mixed tumours in other cancers.

Altered dynamic neural activities in individuals with obsessive-compulsive disorder and comorbid depressive symptoms.

Objectives: Depressive symptoms are the most prevalent comorbidity in individuals with obsessive-compulsive disorder (OCD). The objective of this study was to investigate the dynamic characteristics of resting-state neural activities in OCD patients with depressive symptoms. Methods: We recruited 29 OCD patients with depressive symptoms, 21 OCD patients without depressive symptoms, and 27 healthy controls, and collected data via structural and functional magnetic resonance imaging (fMRI). We analyzed the fMRI results using the dynamic amplitude of low-frequency fluctuation (dALFF) and support vector machine (SVM) techniques. Results: Compared with OCD patients without depressive symptoms, OCD patients with depressive symptoms exhibited an increased dALFF in the left precuneus and decreased dALFF in the right medial frontal gyrus. The SVM indicated that the integration of aberrant dALFF values in the left precuneus and right medial frontal gyrus led to an overall accuracy of 80%, a sensitivity of 79%, and a specificity of 100% in detecting depressive symptoms among OCD patients. Conclusion: Therefore, our study reveals that OCD patients with depressive symptoms display neural activities with unique dynamic characteristics in the resting state. Accordingly, abnormal dALFF values in the left precuneus and right medial frontal gyrus could be used to identify depressive symptoms in OCD patients.

A hot-emitter transistor based on stimulated emission of heated carriers.

Hot-carrier transistors are a class of devices that leverage the excess kinetic energy of carriers. Unlike regular transistors, which rely on steady-state carrier transport, hot-carrier transistors modulate carriers to high-energy states, resulting in enhanced device speed and functionality. These characteristics are essential for applications that demand rapid switching and high-frequency operations, such as advanced telecommunications and cutting-edge computing technologies1-5. However, the traditional mechanisms of hot-carrier generation are either carrier injection6-11 or acceleration12,13, which limit device performance in terms of power consumption and negative differential resistance14-17. Mixed-dimensional devices, which combine bulk and low-dimensional materials, can offer different mechanisms for hot-carrier generation by leveraging the diverse potential barriers formed by energy-band combinations18-21. Here we report a hot-emitter transistor based on double mixed-dimensional graphene/germanium Schottky junctions that uses stimulated emission of heated carriers to achieve a subthreshold swing lower than 1 millivolt per decade beyond the Boltzmann limit and a negative differential resistance with a peak-to-valley current ratio greater than 100 at room temperature. Multi-valued logic with a high inverter gain and reconfigurable logic states are further demonstrated. This work reports a multifunctional hot-emitter transistor with significant potential for low-power and negative-differential-resistance applications, marking a promising advancement for the post-Moore era.

Design and Evaluation of 3-Phenyloxetane Derivative Agonists of the Glucagon-Like Peptide-1 Receptor.

Various small molecule GLP1R agonists have been developed and tested for treating type 2 diabetes (T2DM) and obesity. However, many of these new compounds have drawbacks, such as potential hERG inhibition, lower activity compared to natural GLP-1, limited oral bioavailability in cynomolgus monkeys, and short duration of action. Recently, a new category of 3-phenyloxetane derivative GLP1R agonists with enhanced hERG inhibition has been discovered. Using an AIDD/CADD method, compound 14 (DD202-114) was identified as a potent and selective GLP1R agonist, which was chosen as a preclinical candidate (PCC). Compound 14 demonstrates full agonistic efficacy in promoting cAMP accumulation and possesses favorable drug-like characteristics compared to the clinical drug candidate Danuglipron. Additionally, in hGLP-1R knock-in mice, compound 14 displayed a sustained pharmacological effect, effectively reducing blood glucose levels and food intake. These findings suggest that compound 14 holds promise as a future treatment option for T2DM and obesity, offering improved properties.

Exploring the effect of active components in oil tree peony seed meal on swine disease resistance and its potential mechanisms based on network pharmacology and molecular docking.

This study aims to explore the feasibility of using network pharmacology and molecular docking technology to predict the effects of active components from oil tree peony seed meal (PSM) on swine diseases. Ten active components of PSM were screened through literature search. The results showed that the average number of cross genes between the potential target genes of PSM active components and each swine disease target gene accounted for 7.64% of the total number of swine disease target genes. The GO enrichment analysis indicates that the assumed target is widely present in swine. The KEGG enrichment analysis results showed that these putative genes were involved in various cancer progression pathways, signaling pathways, and hormone regulatory pathways. A total of 8 core targets were obtained through protein-protein interaction networks analysis. It was found that three pathways are not only associated with kinds of swine disease, but also with multiple core targets of PSM active components. In addition, the molecular docking results indicate that the core ingredients have strong affinity with hub genes. The research suggests that the active components of PSM may intervene in swine diseases through multiple components, targets, and pathways.

Comparative Evaluation Between Cutting of the Intersphincteric Space vs Cutting Seton in High Anal Fistula: A Randomized Controlled Trial.

BACKGROUND: This study compared the efficacy of cutting of the intersphincteric space (COIS) with cutting seton (CS) procedure in treating high anal fistula. METHODS: Patients diagnosed with high anal fistula were allocated into groups, who randomly received COIS and CS procedures. The primary outcome was wound healing time. Secondary outcomes included surgical parameters (operation time, hospital stay, and hospitalization expense), anal sphincter function, wound pain, wound size, clinical efficacy, recurrence after 12 months of follow-up, and complications. RESULTS: A total of 72 patients participated (36 in each group). The wound healing time was notably shorter in the COIS group than the CS group (35.75 ± 11.15 vs. 55.69 ± 13. 42 days; P< 0.001). The COIS group also demonstrated superior basic surgical parameters compared to the CS group (P< 0.001). Postoperatively, the COIS group exhibited significantly higher anal resting pressure and anal maximum contractile pressure than the CS group at 3 months postoperatively (58.39 ± 6.72 vs. 51.25 ± 4.33 mmHg; P< 0.001 and 143.72 ± 8.25 vs. 126.75 ± 11.49 mmHg; P< 0.001). The Wexner incontinence score at 3 months post-operation in the COIS group was significantly lower than in the CS group (0.50;0.00,1.00 vs. 3.00; 3.00,4.00; P< 0.001). The recurrence rate was 2.78% in the COIS group and 8.33% in the CS group without statistically difference (P= 0.607). CONCLUSION: In comparison to the CS procedure, COIS appears to be an effective treatment option for high anal fistulas, offering quicker wound healing time, enhanced sphincter function, less pain, minimal invasiveness, and cost-efficiency, while maintaining a high healing rate and low recurrence rate.