An energy and information analysis method of logic gates based on stochastic thermodynamics.

To reduce the energy consumption of logic gates in digital circuits, the size of transistors approaches the mesoscopic scale, e.g. sub-7 nanometers. However, existing energy consumption analysis methods exhibit various deviation for logic gates when the nonequilibrium information processing of mesoscopic scale transistors with ultra-low voltages is analyzed. Based on the stochastic thermodynamics theory, an information energy ratio method is proposed for the energy consumption estimation of XOR gates composed of mesoscopic scale transistors. The proposed method provides a new insight to quantify the transformation between the information capacity and energy consumption for XOR gates and extending to other logic gates. Utilizing the proposed analysis method, the supply voltage of the parity check circuit can be optimized by numerical simulations without expensive and complex practical measurements. The information energy ratio is the first analytical method to quantify the energy and information transformation of logic gates at the mesoscopic scale.

Gender-specific microbial signatures in saliva: Unveiling the association between the oral microbiome and the pathogenesis of glioma.

The intricate interplay between the human oral microbiome and systemic health is increasingly being recognized, particularly in the context of central nervous system pathologies such as glioblastoma. In this study, we aimed to elucidate gender-specific differences in the salivary microbiome of glioma patients by utilizing 16S rRNA sequencing data from publicly available salivary microbiome datasets. We conducted comprehensive bioinformatics analysis, encompassing quality control, noise reduction, species classification, and microbial community composition analysis at various taxonomic levels. Machine learning algorithms were employed to identify microbial signatures associated with glioma. When compared to healthy controls, our analysis revealed distinct differences in the salivary microbiota of glioma patients. Notably, the genera Leptotrichia and Atopobium exhibited significant variations in abundance between genders. Leptotrichia was prevalent in healthy females but exhibited a reduced abundance in female glioma patients. In contrast, Atopobium was more abundant in male glioma patients. These findings suggest that hormonal influences might play a role in shaping the salivary microbiome and its association with glioma. We utilized a combination of LASSO-logistic regression and random forest models for feature selection, and identified key microbial features that differentiated glioma patients from healthy controls. We developed a diagnostic model with high predictive accuracy and area under the curve and principal component analysis metrics confirmed its robustness. The analysis of microbial markers, including Atopobium and Leptotrichia, highlighted the potential of the salivary microbiota as a non-invasive biomarker for the diagnosis and prognosis of glioma. Our findings highlight significant gender-specific disparities in the salivary microbiome of patients with glioma, offering new insights into the pathogenesis of glioma and paving the way for innovative diagnostic and therapeutic strategies. The use of saliva as a diagnostic fluid, given its ease of collection and non-invasive nature, holds immense promise for monitoring systemic health and the trajectory of disease. Future research should focus on investigating the underlying mechanisms by which the salivary microbiome influences the development of glioma and identifying potential microbiome-targeted therapies to enhance the management of glioma.

Drug-drug interactions of simnotrelvir/ritonavir: an open-lable, fixed-sequence, two-period clinical trial.

OBJECTIVES: Simnotrelvir is a small molecule highly specific 3C-like protease inhibitor for anti-SARS-CoV-2 and was approved as a combination drug with ritonavir (simnotrelvir/ritonavir) in China. Simnotrelvir is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), and a weak inhibitor of CYP3A. Ritonavir is a substrate and inhibitor of CYP3A and an inhibitor of P-gp. Hence, the drug-drug interaction (DDI) potential of simnotrelvir/ritonavir should be investigated. METHODS: This DDI study was an open-label, fixed-sequence, two-period Phase I clinical trial in Chinese healthy adult subjects, divided into 3 cohorts, including simnotrelvir/ritonavir co-administrated with a strong CYP3A and P-gp inhibitor (itraconazole) and inducer (rifampicin), and with a specific CYP3A substrate (midazolam). RESULTS: The results demonstrated that compared to administration of simnotrelvir/ritonavir alone, the co-administration with itraconazole increased the geometric least-square mean ratio (GMR) of the expose (AUC0-t) of simnotrelvir by 25% (GMR 125%, 90% confidence interval (CI) 114% - 137%), whereas co-administration with rifampicin significantly decreased the AUC0-t of simnotrelvir by 81.5% (GMR 18.5%, 90% CI 16.4% - 20.9%). Notably, simnotrelvir/ritonavir increased the AUC0-t of midazolam by 16.69-fold (GMR 1769%, 90% CI 1551% - 2018%). The co-administration of simnotrelvir/ritonavir and rifampicin caused the increased amount and severity of treatment-emergent adverse events, especially hepatotoxicity. CONCLUSIONS: The co-administration of simnotrelvir/ritonavir with CYP3A and P-gp inhibitors can be safely used, while the co-administration with CYP3A and P-gp strong inducer should be avoided to minimize the risk of under-exposure. Co-administration of midazolam with simnotrelvir/ritonavir increased systemic exposure of midazolam. GOV IDENTIFIER: NCT05665647.

Added value of artificial intelligence solutions for arterial stenosis detection on head and neck CT angiography: A randomized crossover multi-reader multi-case study.

PURPOSE: The purpose of this study was to investigate the added value of artificial intelligence (AI) solutions for the detection of arterial stenosis (AS) on head and neck CT angiography (CTA). MATERIALS AND METHODS: Patients who underwent head and neck CTA examinations at two hospitals were retrospectively included. CTA examinations were randomized into group 1 (without AI-washout-with AI) and group 2 (with AI-washout-without AI), and six readers (two radiology residents, two non-neuroradiologists, and two neuroradiologists) independently interpreted each CTA examination without and with AI solutions. Additionally, reading time was recorded for each patient. Digital subtraction angiography was used as the standard of reference. The diagnostic performance for AS at lesion and patient levels with four AS thresholds (30 %, 50 %, 70 %, and 100 %) was assessed by calculating sensitivity, false-positive lesions index (FPLI), specificity, and accuracy. RESULTS: A total of 268 patients (169 men, 63.1 %) with a median age of 65 years (first quartile, 57; third quartile, 72; age range: 28-88 years) were included. At the lesion level, AI improved the sensitivity of all readers by 5.2 % for detecting AS ≥ 30 % (P < 0.001). Concurrently, AI reduced the FPLI of all readers and specifically neuroradiologists for detecting non-occlusive AS (all P < 0.05). At the patient level, AI improved the accuracy of all readers by 4.1 % (73.9 % [1189/1608] without AI vs. 78.0 % [1254/1608] with AI) (P < 0.001). Sensitivity for AS ≥ 30 % and the specificity for AS ≥ 70 % increased for all readers with AI assistance (P = 0.01). The median reading time for all readers was reduced from 268 s without AI to 241 s with AI (P< 0.001). CONCLUSION: AI-assisted diagnosis improves the performance of radiologists in detecting head and neck AS, and shortens reading time.

Effects of four kinds of improver on fermentation characteristics of gluten-free rice dough.

Rice is commonly utilized as a wheat bread substitute due to its low allergenicity. However, rice bread faces challenges in processing efficiency and the formation of a cohesive gel network structure, resulting in suboptimal taste Hence, this study compared four improvers-trypsin, whey protein (WPC), hydroxypropyl methyl cellulose (HPMC), and molecularly distilled monoglycerides (GMSs). The impacts of the four improvers on the processing attributes of rice dough were comprehensively assessed across fermentation, moisture content analysis, rheology, heat stability, and pasting characteristics. The findings indicated that the incorporation of trypsin, HPMC, and WPC resulted in 107%, 61%, and 1% increases in gas production of fermented rice dough, respectively, while reducing the regrowth values to 564.00 ± 7.21, 176.67 ± 0.58, and 611.00 ± 3.61 cP. Notably, the air-holding capacity of HPMC-fermented rice dough exhibited a 7% enhancement. All four types of improvers raised the enthalpy of melting (ΔH) and the difference in melting point (ΔT) of fermented rice doughs, with trypsin enhancing ΔH by 44% and ΔT by 40%. GMS, HPMC, and WPC increased the degree of water incorporation in fermented doughs. This study could serve as a benchmark for enhancing the fermentation attributes of rice dough and establish a groundwork for the future advancement of gluten-free dietary options. PRACTICAL APPLICATION: The thorough analysis conducted in this experiment provides a theoretical framework for rice dough preparation during the fermentation process, addressing the dietary needs of individuals with coeliac disease and those following a gluten-free diet. This study also paves the way for the development of improved gluten-free rice products in future research pursuits.

Transcriptional re-programming of liver-resident iNKT cells into T-regulatory type-1-like liver iNKT cells involves extensive gene de-methylation.

Unlike conventional CD4+ T cells, which are phenotypically and functionally plastic, invariant NKT (iNKT) cells generally exist in a terminally differentiated state. Naïve CD4+ T cells can acquire alternative epigenetic states in response to different cues, but it remains unclear whether peripheral iNKT cells are epigenetically stable or malleable. Repetitive encounters of liver-resident iNKT cells (LiNKTs) with alpha-galactosylceramide (αGalCer)/CD1d-coated nanoparticles (NPs) can trigger their differentiation into a LiNKT cell subset expressing a T regulatory type 1 (TR1)-like (LiNKTR1) transcriptional signature. Here we dissect the epigenetic underpinnings of the LiNKT-LiNKTR1 conversion as compared to those underlying the peptide-major histocompatibility complex (pMHC)-NP-induced T-follicular helper (TFH)-to-TR1 transdifferentiation process. We show that gene upregulation during the LINKT-to-LiNKTR1 cell conversion is associated with demethylation of gene bodies, inter-genic regions, promoters and distal gene regulatory elements, in the absence of major changes in chromatin exposure or deposition of expression-promoting histone marks. In contrast, the naïve CD4+ T cell-to-TFH differentiation process involves extensive remodeling of the chromatin and the acquisition of a broad repertoire of epigenetic modifications that are then largely inherited by TFH cell-derived TR1 cell progeny. These observations indicate that LiNKT cells are epigenetically malleable and particularly susceptible to gene de-methylation.

Cost-effectiveness analysis of durvalumab plus tremelimumab as first-line therapy in patients with unresectable hepatocellular carcinoma.

Background: The HIMALAYA trial found that durvalumab plus tremelimumab significantly prolonged progression-free survival and overall survival in patients with unresectable hepatocellular carcinoma (HCC) compared with sorafenib. Objective: This study aimed to investigate the cost-effectiveness of durvalumab plus tremelimumab compared with sorafenib in the first-line HCC setting. Design: A Markov model-based cost-effectiveness analysis. Methods: We created a Markov model to compare healthcare costs and clinical outcomes of HCC patients treated with durvalumab plus tremelimumab in the first-line setting compared with sorafenib. We estimated transition probabilities from randomized trials. Lifetime direct healthcare costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were calculated for first-line durvalumab plus tremelimumab compared with sorafenib from a US payer's perspective. Results: In the base case, first-line durvalumab plus tremelimumab was associated with an improvement of 0.29 QALYs compared with sorafenib. While both treatment strategies were associated with considerable lifetime expenditures, first-line durvalumab plus tremelimumab was less expensive than sorafenib ($188,405 vs $218,584). The incremental net monetary benefit for durvalumab plus tremelimumab versus sorafenib was $72,762 (valuing QALYs at $150,000 each). The results of durvalumab plus tremelimumab were better in terms of costs and health outcomes in patients with HBV-related HCC and high alpha-fetoprotein levels. Conclusion: First-line durvalumab plus tremelimumab was estimated to be dominant for the treatment of unresectable HCC compared with sorafenib from a US payer's perspective.

An integration of genome-wide survey, homologous comparison and gene expression analysis provides a basic framework for the ZRT, IRT-like protein (ZIP) in foxtail millet.

Essential mineral elements such as zinc and iron play a crucial role in maintaining crop growth and development, as well as ensuring human health. Foxtail millet is an ancient food crop rich in mineral elements and constitutes an important dietary supplement for nutrient-deficient populations. The ZIP (ZRT, IRT-like protein) transporters are primarily responsible for the absorption, transportation and accumulation of Zn, Fe and other metal ions in plants. Here, we identified 14 ZIP transporters in foxtail millet (SiZIP) and systematically characterized their phylogenetic relationships, expression characteristics, sequence variations, and responses to various abiotic stresses. As a result, SiZIPs display rich spatiotemporal expression characteristics in foxtail millet. Multiple SiZIPs demonstrated significant responses to Fe, Cd, Na, and K metal ions, as well as drought and cold stresses. Based on homologous comparisons, expression characteristics and previous studies, the functions of SiZIPs were predicted as being classified into several categories: absorption/efflux, transport/distribution and accumulation of metal ions. Simultaneously, a schematic diagram of SiZIP was drawn. In general, SiZIPs have diverse functions and extensively involve in the transport of metal ions and osmotic regulation under abiotic stresses. This work provides a fundamental framework for the transport and accumulation of mineral elements and will facilitate the quality improvement of foxtail millet.

Gene co-expression network and differential expression analyses reveal key genes for weaning weight in Simmental-Holstein crossbred cattle.

Weaning weight is a key indicator of the early growth performance of cattle. An understanding of the genetic mechanisms underlying weaning weight will help increase the accuracy of selection of breeding animals. In order to identify candidate genes associated with weaning weight in Simmental-Holstein crossbred cattle, this study generated RNA-Sequencing (RNA-seq) data from 86 crossbred calves (37 males and 49 famales) and measured their weaning weight and body size traits (wither height, body length, chest girth, rump width, and rump length). Differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) were performed. A total of 498 differentially expressed genes (DEGs) were identified between the low weaning weight (LWW) group and the high weaning weight (HWW) group. Weaning weight was transcriptionally correlated (FDR < 0.05) with four of the eleven co-expression gene modules. By intersecting DEGs and hub genes of the four modules, we identified a final set of 37 candidate genes enriched in growth, development, or immune-related processes. In addition, one co-expression module was significantly correlated with all the five body size traits (P < 0.05), from which MX1 was identified as a key candidate gene through protein-protein interaction (PPI) analysis of hub genes. Further evidence from cattle transcriptome-wide association study analysis (TWAS) and human phenome-wide association study (PheWAS) validated significant associations of CACNA1S, SEMA7A, VCAN, CD101, CD19, and CSF2RB with growth and development traits (P < 0.05). Notably, CACNA1S and CD19 were also associated with typical immune traits such as B cell proliferation, differentiation, and activation. In conclusion, this study reveals new candidate genes significantly associated with weaning weight in Simmental-Holstein crossbred cattle, providing a basis for further exploration of the genetic mechanisms behind growth traits of cattle.

Dietary vitamin B3 supplementation induces the antitumor immunity against liver cancer via biased GPR109A signaling in myeloid cell.

The impact of dietary nutrients on tumor immunity remains an area of ongoing investigation, particularly regarding the specific role of vitamins and their mechanism. Here, we demonstrate that vitamin B3 (VB3) induces antitumor immunity against liver cancer through biased GPR109A axis in myeloid cell. Nutritional epidemiology studies suggest that higher VB3 intake reduces liver cancer risk. VB3 supplementation demonstrates antitumor efficacy in multiple mouse models through alleviating the immunosuppressive tumor microenvironment (TME) mediated by tumor-infiltrating myeloid cell, thereby augmenting effectiveness of immunotherapy or targeted therapy in a CD8+ T cell-dependent manner. Mechanically, the TME induces aberrant GPR109A/nuclear factor κB (NF-κB) activation in myeloid cell to shape the immunosuppressive TME. In contrast, VB3 activates ß-Arrestin-mediated GPR109A degradation and NF-κB inhibition to suppress the immunosuppressive polarization of myeloid cell, thereby activating the cytotoxic function of CD8+ T cell. Overall, these results expand the understanding of how vitamins regulate the TME, suggesting that dietary VB3 supplementation is an adjunctive treatment for liver cancer.

Self-Polymerized Tough and High-Entanglement Zwitterionic Functional Hydrogels.

Zwitterionic hydrogels exhibit great potential in biomedical applications due to their antifouling properties and biocompatibility. However, the single-network structure of pure zwitterionic hydrogels leads to a low toughness and strength, limiting their application in biomedical fields. In this work, a high entanglement sulfobetaine methacrylate-dopamine hydrogel (SBMA-DA-PE) with low cross-linker content and high monomer concentration is prepared by using a dopamine oxidative radical polymerization method. Compared to a regular zwitterionic hydrogel, the SBMA-DA-PE hydrogel exhibits a 5-fold increase in tensile fracture stress and a 10-fold increase in compressive fracture stress. The SBMA-DA-PE hydrogel possesses excellent mechanical properties (the maximum compressive stress ≥4.85 MPa, the maximum compressive strain ≥90%). Besides, the non-covalent interactions between catechol or ortho-quinones within the SBMA-DA-PE hydrogel, combined with strong intermolecular electrostatic interactions, endow the SBMA-DA-PE hydrogel with great self-healing capabilities and fatigue resistance. The SBMA-DA-PE hydrogel demonstrates low swellability and possesses good antifouling properties. Furthermore, the good printability and conductivity of the tough SBMA-DA-PE hydrogel endows it with new possibilities for developing biological 3D scaffolds and electronic devices. Overall, this work provides new insights into the preparation of zwitterionic hydrogels with high mechanical strength and multi-functionality for biomedical applications.

Flow Cytometry Sorting for Random Access in DNA Data Storage: Encapsulation for Enhanced Stability and Sequence Integrity of DNA.

As digital data undergo explosive growth, deoxyribonucleic acid (DNA) has emerged as a promising storage medium due to its high density, longevity, and ease of replication, offering vast potential in data storage solutions. This study focuses on the protection and retrieval of data during the DNA storage process, developing a technique that employs flow cytometry sorting (FCS) to segregate multicolored fluorescent DNA microparticles encoded with data and facilitating efficient random access. Moreover, the encapsulated fluorescent DNA microparticles, formed through layer-by-layer self-assembly, preserve structural and sequence integrity even under harsh conditions while also supporting a high-density DNA payload. Experimental results have shown that the encoded data can still be successfully recovered from encapsulated DNA microparticles following de-encapsulation. We also successfully demonstrated the automated encapsulation process of fluorescent DNA microparticles using a microfluidic chip. This research provides an innovative approach to the long-term stability and random readability of DNA data storage.

Ag+-Induced Assembly of Pt Clusters for Photocatalytic Hydrogen Production.

Cluster-assembled nanowires provide a unique strategy for the preparation of high-performance nanostructures. However, existing preparations are limited by complex processes and harsh reaction conditions. Here, Ag+ ions were utilized as a novel structure-directing agent to generate the self-assembly of Pt clusters to form ultrafine nanowires with a diameter of less than 5 nm. Electrospray ionization mass spectrometry (ESI-MS) and extended X-ray absorption fine structure (EXAFS) characterizations demonstrated that every Ag+ bridged two [Pt3(CO)3(µ2-CO)3]n2- clusters through coordination and formed a sandwich-like structure of [Pt3(CO)3(µ2-CO)3]nAg[Pt3(CO)3(µ2-CO)3]m3-. As a result, multiple sandwich-like structures of [Pt3(CO)3(µ2-CO)3]nAg[Pt3(CO)3(µ2-CO)3]m3- were established by Ag+ to form Pt nanowire superstructures {[Pt3(CO)6]nAg[Pt3(CO)6]mAg[Pt3(CO)6]x}∞ (abbreviated as Ag-Pt NWS). Our results demonstrate that the Pt nanowire superstructures showed promising cocatalytic performance for photocatalytic H2 production with the involvement of Ag+, which promises a desirable way to develop advanced functional nanomaterials.

Structures of Th4+ aqueous solutions: insights from AIMD and metadynamics simulations.

Solution chemistry of actinide ions is critical to understanding the solvation behaviors and hydrolysis process. Using tetravalent thorium ion Th4+ as a representative example, we investigate the local structures and dynamic behaviors of hydrated Th4+ ions by ab initio molecular dynamics (AIMD) simulations using the recently developed norm-conserving pseudopotentials and basis sets optimized for actinides (J.-B. Lu et al., J. Chem. Theory Comput. 2021, 17, 3360-3371). AIMD simulations reveal two distinct solvation shells, with the first shell comprising 9 water molecules at approximately rTh-O = 2.50 Å and exhibiting a tricapped trigonal prism geometry. These conclusions are confirmed through metadynamics simulations and further structural analysis. AIMD simulations also show the slight effect of temperature and counterions on the structure of the solution. The structured solvation shells of the highly charged Th4+ ion with the specific geometry, distinct from the structure of liquid water, lead to corresponding structural changes in the hydrogen bond network in water. Additionally, beyond the solvent-shared ion pair (SIP) state observed in the unbiased AIMD simulations, the metadynamics simulations reconstruct a two-dimensional free energy surface that clearly indicates the potential stability of the contact ion pair (CIP) state in the system with Cl- as a counterion. The findings in this work provide insights into the solution chemistry of actinides and serve as a reference for studying other actinide solution systems.

SCAMP1 silencing inhibits proliferation by attenuating multiple pro-survival signaling pathways in gastric cancer.

Secretory carrier-associated membrane protein 1 (SCAMP1) is the most universally expressed member of the SCAMP family, and its ability to facilitate endocytosis was demonstrated approximately two decades ago. Nevertheless, its roles in cancer biology are largely unknown, although its expression is significantly increased in most cancer types. Herein, we examined the expression of SCAMP1 in gastric cancer (GC) tissues and found that it was aberrantly increased and positively correlated with tumor size and lymph node metastasis. More importantly, increased SCAMP1 expression was associated with poor prognosis in patients with GC. Functional experiments demonstrated that SCAMP1 knockdown markedly suppressed the proliferation of GC cells in vitro and in vivo. RNA sequencing assays demonstrated that SCAMP1 knockdown altered the expression profile of GC cells, and a significant portion of the altered genes were enriched in receptor tyrosine kinases and their related downstream signaling pathways. Immunoblotting confirmed that the Akt/MAPK/Stat signaling pathway was strongly attenuated in GC cells with SCAMP1 depletion. Taken together, these results demonstrated that SCAMP1 drives hyperproliferation in GC cells, thus suggesting that further investigation into the mechanisms and translational value of SCAMP1 in treating patients with GC is warranted.

Functional Study of desKR: a Lineage-Specific Two-Component System Positively Regulating Staphylococcus aureus Biofilm Formation.

Purpose: Biofilms significantly contribute to the persistence and antibiotic resistance of Staphylococcus aureus infections. However, the regulatory mechanisms governing biofilm formation of S. aureus remain not fully elucidated. This study aimed to investigate the function of the S. aureus lineage-specific two-component system, desKR, in biofilm regulation and pathogenicity. Methods: Bioinformatic analysis was conducted to assess the prevalence of desKR across various S. aureus lineages and to examine its structural features. The impact of desKR on S. aureus pathogenicity was evaluated using in vivo mouse models, including skin abscess, bloodstream infection, and nasal colonization models. Crystal violet staining and confocal laser scanning microscopy were utilized to examine the impact of desKR on S. aureus biofilm formation. Mechanistic insights into desKR-mediated biofilm regulation were investigated by quantifying polysaccharide intercellular adhesin (PIA) production, extracellular DNA (eDNA) release, autolysis assays, and RT-qPCR. Results: The prevalence of desKR varied among different S. aureus lineages, with notably low carriage rates in ST398 and ST59 lineages. Deletion of desKR in NCTC8325 strain resulted in decreased susceptibility to ß-lactam and glycopeptide antibiotics. Although desKR did not significantly affect acute pathogenicity, the ΔdesKR mutant exhibited significantly reduced nasal colonization and biofilm-forming ability. Overexpression of desKR in naturally desKR-lacking strains (ST398 and ST59) enhanced biofilm formation, suggesting a lineage-independent effect. Phenotypic assays further revealed that the ΔdesKR mutant showed reduced PIA production, decreased eDNA release, and lower autolysis rates. RT-qPCR indicated significant downregulation of icaA, icaD, icaB, and icaC genes, along with upregulation of icaR, whereas autolysis-related genes remained unchanged. Conclusion: The desKR two-component system positively regulates S. aureus biofilm formation in a lineage-independent manner, primarily by modulating PIA synthesis via the ica operon. These findings provide new insights into the molecular mechanisms of biofilm formation in S. aureus and highlight desKR as a potential target for therapeutic strategies aimed at combating biofilm-associated infections.

Feasibility and Acceptability of a Trauma-informed Intervention to Leverage Caregivers in Preventing Opioid Use Among Youth Involved in the Legal System.

Youth in the legal system (YILS) report high rates of substance use (SU), complex family/social relationships, and chronic trauma. The current study tested the feasibility of a prevention intervention, Trust-based Relational Intervention® (TBRI®), that leverages family systems by strengthening connection and providing emotional and instrumental guidance and support. TBRI includes the primary TBRI Intervention, comprised of Caregiver Training, Youth Training, and joint youth-caregiver Nurture Groups, and TBRI Family Coaching. With a sample of eight youth-caregiver dyads, the study adopted a mixed-methods design with a multi-informant approach to fulfill two goals: (1) testing TBRI as a prevention intervention for opioid use (OU), other SU, and related issues, and (2) testing the feasibility and acceptability of the TBRI Intervention by virtual delivery. Session attendance and completion rates demonstrated feasibility of recruiting and retaining participants and intervention fidelity. Preliminary results were reported on intervention outcomes, including OU and other SU, illegal activities, and educational attainment. Pre- and post-intervention comparisons showed decreases in youth negative urgency, conduct problems, and hyperactivity. Caregiver and staff participants responded favorably to TBRI and its virtual delivery; youth were more capable of expressing their needs and acknowledged the importance of families in preventing problems after discharge from secure facilities. While acknowledging sufficiency of intervention content, caregivers expressed the desire for more sessions. Results demonstrate the feasibility and acceptability of a trauma-informed, attachment-based prevention intervention for youth and families in contact with the legal system. TBRI is a promising approach for preventing the initiation or escalation of OU among YILS.

Boron-Doped Single-Molecule van der Waals Diode.

Single-molecule diode was the first proposed device in molecular electronics. Despite the great efforts and advances over 50 years, the reported rectification ratios, the most critical parameter of a diode, remain moderate for the single-molecule diode. Herein, we report an approach to achieve a larger rectification ratio by adopting the combined strategies of p-type boron doping, the single-layer graphene nodes, and the van der Waals layer-by-layer architecture. Measured current-voltage curves showed one of the as-fabricated single-molecule diodes hit an unprecedented large rectification ratio of 457 at ±1 V. Break junction operations and spectroscopic measurements revealed the three-atom-thick configuration of the single-molecule diodes. With the experimental and theoretical calculation results, we demonstrated the doped boron atoms induced holes to redistribute the electron density, making the asymmetric coupling at positive and negative biases, and the van der Waals interaction promoted asymmetric coupling and significantly boosted diode performance.

Elucidation of the molecular mechanism of type 2 diabetes mellitus affecting the progression of nonalcoholic steatohepatitis using bioinformatics and network pharmacology: A review.

Increasing evidence suggests that patients with diabetes are at increased risk of developing nonalcoholic steatohepatitis (NASH), but the underlying mechanisms that affect the progression of NASH remain unclear. In this study, we used bioinformatics and network pharmacology methods to explore the differentially expressed genes of NASH and the related genes of type 2 diabetes mellitus, and a total of 46 common targets were obtained. Gene ontology showed that the common targets were mainly involved in biological processes such as glucocorticoid, hormone, and bacterium responses. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis signal pathways were mainly in colorectal cancer, amphetamine addition, the peroxisome proliferator-activated receptor signaling pathway, and the toll-like receptor signaling pathway. The protein-protein interaction network identified 8 hub genes, and the co-expression network was analyzed to obtain 7 related functions and mutual proportions of hub genes. A total of 120 transcription factors were predicted for hub genes. Hub genes were closely related to immune cells, including neutropils and eosinophils. In addition, we identified 15 potential candidate drugs based on hub genes that are promising for the treatment of NASH. Type 2 diabetes mellitus can affect the progression of NASH by changing hormone levels and inflammatory responses through multiple targets and signaling pathways. Eight hub genes are expected to be potential targets for subsequent treatment.

Impact of staged goal-directed fluid therapy on postoperative pulmonary complications in patients undergoing McKeown esophagectomy: a randomized controlled trial.

BACKGROUND: Our aim was to evaluate the influence of staged goal directed therapy (GDT) on postoperative pulmonary complications (PPCs), intraoperative hemodynamics and oxygenation in patients undergoing Mckeown esophagectomy. METHODS: Patients were randomly divided into three groups, staged GDT group (group A, n = 56): stroke volume variation (SVV) was set at 8-10% during the one lung ventilation (OLV) stage and 8-12% during the two lung ventilation (TLV) stage, GDT group (group B, n = 56): received GDT with a target SVV of 8-12% During the entire surgical procedure, and control group (group C, n = 56): conventional fluid therapy was administered by mean arterial pressure (MAP), central venous pressure (CVP), and urine volume. The primary outcome was the incidence of postoperative pulmonary complications within Postoperative days (POD) 7. The secondary outcomes were postoperative lung ultrasound (LUS) B-lines artefacts (BLA) scoring, incidence of other complications, the length of hospital stay, intraoperative hemodynamic and oxygenation indicators included mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), cardiac output (CO), oxygenation index (OI), respiratory indices (RI), alveolar-arterial oxygen difference (Aa-DO2). RESULTS: Patients in group A and group B had a lower incidence of PPCs (7/56 vs. 17/56 and 9/56 vs. 17/56, p < 0.05), and a fewer B-lines score on postoperative ultrasound (4.61 ± 0.51 vs. 6.15 ± 0.74 and 4.75 ± 0.62 vs. 6.15 ± 0.74, p < 0.05) compared to group C. The CI, CO, MAP, and OI were higher in group A compared to group B and group C in the stage of thoracic operation. During the abdominal operation stage, patients in group A and group B had a better hemodynamic and oxygenation indicators than group C. CONCLUSIONS: In comparison to conventional fluid therapy, intraoperative staged GDT can significantly reduce the incidence of postoperative pulmonary complications in patients undergoing McKeown esophagectomy, facilitating patient recovery. Compared to GDT, it can improve intraoperative oxygenation and stabilize intraoperative hemodynamics in patients. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry on 24/11/2021 (ChiCTR2100053598).