Encapsulated papillary carcinoma of breast: Comparative study of multimodal ultrasound manifestations and pathological features.

OBJECTIVE: To investigate the conventional ultrasound (US), contrast-enhanced ultrasound (CEUS) manifestations and the corresponding histopathological characteristics of patients diagnosed with breast encapsulated papillary carcinoma (EPC) and to explore the value of CEUS in diagnosis of EPC. METHODS: The clinical, pathological, US, and CEUS features of 16 patients (17 lesions) with EPC confirmed by postoperative histopathology were retrospectively analyzed. RESULTS: EPC was prevalent in the postmenopausal women. The majority of conventional US images of EPC showed complex cystic and solid masses with circumscribed margins (70.6%), enhanced posterior echo (94.1%), no sonographic calcification (88.2%), rich blood flow in the solid components within lesions (70.6%) on Color Doppler flow imaging, and high resistance index of blood flow (94.1%). Moreover, CEUS showed mainly centripetal hyperenhancement of the solid components within the lesions with irregular outline, and the enhancement area of the whole masses was essentially the same as the B-mode US area. CONCLUSIONS: EPC typically presents as a complex cystic and solid mass. CEUS is helpful to clarify the extent of the solid component and facilitate preoperative core-needle biopsy. A comprehensive evaluation by CEUS is valuable for diagnosing EPC and combining it with clinical features are helpful to further improve the diagnosis of this rare kind of breast cancer.

Integrated identification and detection of hydration state and its evolution using terahertz technology.

The accurate detection of dehydration processes in hydrated drugs can reveal various intermolecular vibration modes mediated by hydrogen bonds between water molecules and other components, which underpin the further development of pharmaceutical science, food safety and biophysics. Herein, terahertz (THz) technology is utilized to investigate the dehydration state of d(+)-Raffinose pentahydrate (Rf·5H2O), in conjunction with imaging-based point by point scanning data acquisition and barcodes methods, to establish an innovative platform integrated identification, trace detection, and application capabilities. Our study demonstrates that the dehydration process of Rf·5H2O can be dynamically monitored through the evolution of its THz absorption peaks, offering more precise results compared to XRD and Raman spectroscopies. Moreover, the absorbance spectra data collected at each individual pixel is utilized to build visualized THz images, achieving an ultralow minimum content required for detection of 0.032 µg/(50 µm)2. Additionally, we introduce a THz spectra-barcode conversion system that not only ensures efficient electronic recordkeeping but also enhances user readability, thereby facilitating the practical applications of THz technology.

[Long-term efficacy of oblique lateral interbody fusion combined with vertebral screw fixation for the treatment of lumbar specific infection].

OBJECTIVE: To explore medium and long term efficacy of oblique lateral interbody fusion (OLIF) in treating lumbar specific infection. METHODS: From October 2017 to January 2021, 24 patients with lumbar specific infection were treated by OLIF combined with vertebral screw internal fixation, including 15 males and 9 females, aged from 27 to 61 years old with an average of (43.0±15.0) years old;the courses of disease ranged from 6 to 24 months with an average of (14.0±7.0) months;7 patients with L2-L3, 12 patients with L3-L4 and 5 patients with L4-L5;19 patients with tuberculosis infection and 5 patients with brucella infection. The amount of intraoperative blood loss, operative time and complications were recorded, and erythrocyte sedimentation rate(ESR), C-reactive protein (CRP), visual analogue scale (VAS), Japanese Orthopaedic Association(JOA) score and American Spinal Injury Association (ASIA) rating were compared before and one month after opertaion. RESULTS: All patients were followed up from 9 to 24 months with an average of (13.0±6.0) months. Operative time was (132.5±21.4) min, and intraoperative blood loss was (227.3±43.1) ml. ESR and CRP were decreased from (82.34±18.62) mmol·h-1 and (53.08±21.84) mg·L-1 before operation to (33.52±17.31) mmol·h-1 and (15.48±8.36) mg·L-1 at one month after operation, respectively (P<0.05). VAS was decreased from (7.52±1.36) before opertaion to (1.74±0.87) at one month after operation (P<0.05). JOA was increased from (17.86±3.95) before operation to (24.72±3.19) at one month after operation (P<0.05). Four patients had neurological symptoms before operation, and were classified to grade D according to ASIA classification, who were recovered to grade E at 1 month after operation. One patient was suffered from psoas major muscle injury after operation, and returned to normal at 3 weeks. One patient was suffered from abdominal distension and difficulty in defecation, and relieved after gastrointestinal decompression and enema. No complications such as abdominal organ injury and poor wound healing occurred in all patients. CONCLUSION: OLIF combined with vertebral screw internal fixation is a new minimally invasive surgical method for the treatment of lumbar specific infection, especially the lesion located on the middle lumbar vertebra. It has advantages of less trauma, short operation time, less blood loss, convenient operation, complete removal of the lesion, safety and effectiveness, and has good medium-and long-term efficacy for lumbar specific infection.

Construction and Analysis of Risk Prediction Model of Eosinophilic Chronic Rhinosinusitis With Nasal Polyps: A Cross-Sectional Study in Northwest China.

OBJECTIVE: To provide guidance for clinical endotypes by constructing a risk-predictive model of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). DESIGN: A cross-sectional study. SETTING: Single-centre trial at tertiary medical institutions. PARTICIPANTS: A cross-sectional study included 343 CRSwNP patients divided into ECRSwNP (n = 237) and non-ECRSwNP (n = 106) groups using surgical pathology. MAIN OUTCOME MEASURES: Single-factor and multivariate analysis were used to identify statistically significant variables for constructing a nomogram, including the history of AR, hyposmia score, ethmoid sinus score, BEP and BEC. The model's performance was evaluated based on the receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA). RESULTS: Allergic rhinitis, hyposmia score, ethmoid sinus score, peripheral blood eosinophil percentage (BEP) and eosinophil count (BEC) were retained for the construction nomogram of ECRSwNP. The nomogram exhibited a certain accuracy, with an AUC of 0.897 (95% CI: 0.864-0.930), good agreement in the calibration curve and a 0.891 C-index of internal validation. Moreover, the DCA with a threshold probability between 0.0167 and 1.00 indicated a higher net benefit and greater clinical utility. CONCLUSION: The construction of a predictive risk model of ECRSwNP based on easily accessible factors could assist clinicians in more conveniently defining endotypes to make optimal diagnoses and treatment choices.

Randomized trial of influence of vitamin D on the prevention and improvement of symptomatic COVID-19.

We aimed to investigate the preventive effect of vitamin D2 on COVID-19 and the improvement of symptoms after COVID-19 infection. The study recruited 228 health care workers who tested negative PCR or antigen for COVID-19. Subjects were randomly allocated to vitamin D2 or non-intervention at a ratio 1:1. Subjects recorded PCR or antigen tests and the symptoms of COVID-19 twice a week during the follow-up visit. The concentration of serum 25-hydroxyvitamin D (25(OH)D), C-reaction protein (CRP), complement component C1q and inflammatory cytokines were measured. The rates of COVID-19 infection were 50.5% in the vitamin D2 group and 52.4% in the non-intervention group (P = 0.785). There was no difference in the COVID-19 symptoms between the two groups. The mean 25(OH)D level significantly increased from 14.1 to 31.1 ng/mL after administration (P < 0.001). The difference between the two groups was not significant for the concentrations of CRP, C1q and inflammatory cytokines on the thirtieth day of the trial. According to the second level of vitamin D, there was a 14.3% difference in positive infection rates between the vitamin D adequate (> 30 ng/mL) and deficient groups (< 20 ng/mL). Adequate vitamin D had a tendency to prevent COVID-19.Trial registration: ClinicalTrials.gov NCT05673980, dated: 12/2022.

Cost-effectiveness analysis of rimegepant for on-demand acute treatment of migraine in China.

Purpose: This study assesses the cost-effectiveness of rimegepant for the on-demand acute treatment of migraine in the Chinese population, focusing on headache relief within a 2 h timeframe. Utilizing data from Phase III clinical trials on rimegepant involving Asian populations, this analysis aims to provide essential insights for healthcare decision-making in the context of migraine management in China. Patients and methods: Employing a decision tree model, this research evaluates the cost-effectiveness of rimegepant over a concise 2 h period, exclusively considering its direct market price of 219.00 CNY per dose for on-demand, single-use treatment upon approval in China. This model is based on pain relief outcomes from a clinical trial, categorizing health outcomes by the achievement of pain freedom and alleviation from the most bothersome symptom within two hours post-administration. Results: The study unveils that rimegepant adds 0.0018 quality-adjusted life days (QALD) with an incremental cost-effectiveness ratio (ICER) of 122,166.07 CNY/QALD. Against a daily cost-effectiveness threshold derived from the 2023 per capita GDP of China (734.45 CNY/day), rimegepant falls short of proving its cost-effectiveness. A significant price reduction to approximately 1.32 CNY per dose is required for rimegepant to be considered cost-effective within this framework. Furthermore, a series of sensitivity analyses were conducted to validate the robustness of these results. Conclusion: While rimegepant shows clinical efficacy in providing rapid relief from migraine symptoms, its current pricing exceeds the threshold for cost-effectiveness in the Chinese healthcare setting. This study underscores the need for price adjustments to enhance the accessibility and economic viability of new migraine treatments.

Exploring the impacts of producer services agglomeration on manufacturing carbon emissions: Empirical evidence from China.

This study employs panel data from 30 provinces and cities in China from 2004 to 2019 to empirically estimate the relationship between producer services agglomeration (PSA) and manufacturing carbon emissions. The findings suggest that such agglomeration is beneficial for lowering carbon emissions in manufacturing, and this conclusion passes multiple robustness tests. Heterogeneity analysis results show that PSA in the east and west regions significantly lowers manufacturing carbon emissions, while its impact in the central region is not significant. High-end PSA is beneficial for cutting carbon emissions in manufacturing, but the inhibitory effect of middle- and low-end PSA is not significant. PSA significantly suppresses carbon emissions from capital- and technology-intensive manufacturing, while it has little impact on carbon emissions from labor-intensive manufacturing. Further analysis reveals that PSA has a dual-threshold impact based on absorptive capacity and a single-threshold effect based on infrastructure level on manufacturing carbon emissions. As the absorption capacity crosses the second threshold or the infrastructure level crosses the first threshold, the inhibition effect of PSA on manufacturing carbon emissions begins to become prominent and shows a trend of enhancement. Our research findings provide theoretical and empirical bases for lowering carbon emissions in the manufacturing sector and fostering its ascent to the highest position of the value chain.

Jiedu Xiaozheng Yin extract targets cancer stem cells by Wnt signaling pathway in colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: The clinical application of the traditional Chinese medicinal formula Jiedu Xiaozheng Yin (JXY) for gastrointestinal tumors, particularly colorectal cancer (CRC), is well-established, yet the precise biological mechanism underlying its efficacy in CRC treatment remains elusive. AIMS OF THE STUDY: This study endeavors to unravel the intricate mechanism through which JXY modulates colorectal cancer stem cells, thus elucidating the pathways by which it exerts its potent anti-tumor effects. MATERIALS AND METHODS: In this study, the regulatory impact of JXY on the signaling pathway and function of CRC cells was analyzed through Network pharmacology. The ethyl acetate extract of JXY was detected the major compounds using HPLC and then treated the HCT-116 cells for RNA-Sequencing (RNA-Seq). Protein expression and stemness of HCT-15 and HCT-116 cells following JXY extract treatment were assessed using Western blot analysis and matrigel spheroid assays. Additionally, the ß-catenin transcriptional activity was evaluated using a TOPflash reporter assay with or without Lithium chloride (LiCl) stimulation. Patient-derived organoids of CRC (CRC PDOs) were cultured using a stemness maintenance medium, and their viability was measured using ATP assays after treatment of JXY extract. Furthermore, the anti-tumor efficacy of JXY extract was assessed using a xenograft mice model derived from HCT-15 cells. RESULTS: Network pharmacology emphasized the influence of JXY on cancer stem cells and the Wnt signaling pathway. HPLC analysis confirmed that the JXY extract contained the three most prevalent pharmaceutical compounds among the four herbs documented in the Chinese Pharmacopoeia (rosmarinic acid, quercetin, and kaempferol). RNA-Seq results further elucidated the effect of JXY extract, particularly targeting cancer stem cells and the Wnt signaling pathway. Furthermore, JXY extract inhibited spheroid formation in CRC cells and downregulated CRC CSC markers (CD133, DCLK1, and C-MYC). Additionally, JXY extract suppressed the ß-catenin expression and transcriptional activity as well as the Wnt pathway target proteins, including C-MYC and Cyclin D1. Consistent with findings from cell lines, JXY extract suppressed the growth of CRC PDOs exhibiting stemness characteristics. And JXY extract demonstrated a significant inhibitory effect on tumor growth, C-MYC, and ß-catenin protein levels in xenograft tumors. CONCLUSIONS: These results highlight the novel function of JXY extract in targeting CRC CSCs by regulating Wnt signaling pathway, underscoring its potential as a therapeutic agent for treating CRC.

A new long-acting analgesic formulation for postoperative pain management.

Local anesthetics (LA), as part of multimodal analgesia, have garnered significant interest for their role in delaying the initiation of opioid therapy, reducing postoperative opioid usage, and mitigating both hospitalization duration and related expenses. Despite numerous endeavors to extend the duration of local anesthetic effects, achieving truly satisfactory long-acting analgesia remains elusive. Drawing upon prior investigations, vesicular phospholipid gels (VPGs) emerge as promising candidates for extended-release modalities in small-molecule drug delivery systems. Therefore, we tried to use the amphiphilicity of phospholipids to co-encapsulate levobupivacaine hydrochloride and meloxicam, two drugs with different hydrophilicity, to obtain a long-term synergistic analgesic effect. Initially, the physicochemical attributes of the formulation were characterized, followed by an examination of its in vitro release kinetics, substantiating the viability of extending the release duration of the dual drugs. Sequentially, in vivo investigations encompassing pharmacokinetic profiling and assessment of analgesic efficacy were undertaken, revealing a prolonged release duration of up to 120 h and attainment of optimal postoperative analgesia. Subsequently, inquiries into the mechanism underlying synergistic analgesic effects and safety evaluations pertinent to the delivery strategy were pursued. In summation, we successfully developed a promising formulation to achieve long-acting analgesia.

Explore key genes of Crohn's disease based on glycerophospholipid metabolism: A comprehensive analysis Utilizing Mendelian Randomization, Multi-Omics integration, Machine Learning, and SHAP methodology.

BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic, complex inflammatory condition with increasing incidence and prevalence worldwide. However, the causes of CD remain incompletely understood. We identified CD-related metabolites, inflammatory factors, and key genes by Mendelian randomization (MR), multi-omics integration, machine learning (ML), and SHAP. METHODS: We first performed a mediation MR analysis on 1400 serum metabolites, 91 inflammatory factors, and CD. We found that certain phospholipids are causally related to CD. In the scRNA-seq data, monocytes were categorized into high and low metabolism groups based on their glycerophospholipid metabolism scores. The differentially expressed genes of these two groups of cells were extracted, and transcription factor prediction, cell communication analysis, and GSEA analysis were performed. After further screening of differentially expressed genes (FDR<0.05, log2FC>1), least absolute shrinkage and selection operator (LASSO) regression was performed to obtain hub genes. Models for hub genes were built using the Catboost, XGboost, and NGboost methods. Further, we used the SHAP method to interpret the models and obtain the gene with the highest contribution to each model. Finally, qRT-PCR was used to verify the expression of these genes in the peripheral blood mononuclear cells (PBMC) of CD patients and healthy subjects. RESULT: MR results showed 1-palmitoyl-2-stearoyl-gpc (16:0/18:0) levels, 1-stearoyl-2-arachidonoyl-GPI (18:0/20:4) levels, 1-arachidonoyl-gpc (20:4n6) levels, 1-palmitoyl-2-arachidonoyl-gpc (16:0/20:4n6) levels, and 1-arachidonoyl-GPE (20:4n6) levels were significantly associated with CD risk reduction (FDR<0.05), with CXCL9 acting as a mediation between these phospholipids and CD. The analysis identified 19 hub genes, with Catboost, XGboost, and NGboost achieving AUC of 0.91, 0.88, and 0.85, respectively. The SHAP methodology obtained the three genes with the highest model contribution: G0S2, S100A8, and PLAUR. The qRT-PCR results showed that the expression levels of S100A8 (p = 0.0003), G0S2 (p < 0.0001), and PLAUR (p = 0.0141) in the PBMC of CD patients were higher than healthy subjects. CONCLUSION: MR findings suggest that certain phospholipids may lower CD risk. G0S2, S100A8, and PLAUR may be potential pathogenic genes in CD. These phospholipids and genes could serve as novel diagnostic and therapeutic targets for CD.

Diagnostic efficacy of the contrast-enhanced ultrasound thyroid imaging reporting and data system classification for benign and malignant thyroid nodules.

Background: The contrasted-enhanced ultrasound thyroid imaging reporting and data system (CEUS TI-RADS) is the first international risk stratification system for thyroid nodules based on conventional ultrasound (US) and CEUS. This study aimed to evaluate the diagnostic efficacy of CEUS TI-RADS for benign and malignant thyroid nodules and to assess the related interobserver agreement. Methods: The study recruited 433 patients who underwent thyroid US and CEUS between January 2019 and June 2023 at the Affiliated Hospital of Guangdong Medical University. A retrospective analysis of 467 thyroid nodules confirmed by fine-needle aspiration (FNA) and/or surgery was performed. Further, a CEUS TI-RADS classification was assigned to each thyroid nodule based on the CEUS TI-RADS scoring criteria for the US and CEUS features of the nodule. The nodules were grouped based on their sizes as follows: size ≤1 cm, group A; size >1 and ≤4 cm, group B; and size >4 cm, group C. Multivariate logistic regression was used to analyze independent risk factors for malignant thyroid nodules. Pathological assessment was the reference standard for establishing the sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) of CEUS TI-RADS in diagnosing malignant thyroid nodules. The area under the curve (AUC) in the receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic efficacy of the scoring system in predicting malignancy in three groups of nodules. The intragroup correlation coefficient (ICC) was adopted to assess the interobserver agreement of the CEUS TI-RADS score. Results: Out of the 467 thyroid nodules, 262 were malignant and 205 were benign. Logistic regression analysis revealed that the independent risk factors for malignant thyroid nodules included punctate echogenic foci (P<0.001), taller-than-wide shape (P=0.015), extrathyroidal invasion (P=0.020), irregular margins/lobulation (P=0.036), hypoechoicity on US (P=0.038), and hypoenhancement on CEUS (P<0.001). The AUC for the CEUS TI-RADS in diagnosing malignant thyroid nodules was 0.898 for all nodules, 0.795 for group A, 0.949 for group B, and 0.801 for group C, with the optimal cutoff values of the CEUS TI-RADS being 5 points, 6 points, 5 points, and 5 points, respectively. Among these groups of nodules, group B had the highest AUC, with the SEN, SPE, ACC, PPV, and NPV for diagnosing malignant nodules being 95.9%, 88.1%, 92.8%, 92.6%, and 93.2%, respectively. The ICC of the CEUS TI-RADS classification between senior and junior physicians was 0.862 (P<0.001). Conclusions: In summary, CEUS TI-RADS demonstrated significant efficacy in distinguishing thyroid nodules. Nonetheless, there were variations in its capacity to detect malignant nodules across diverse sizes, and it demonstrate optimal performance in 1- to 4-cm nodules. These findings may serve as important insights for clinical diagnoses.

Enhanced cerebral blood flow similarity of the somatomotor network in chronic insomnia: Transcriptomic decoding, gut microbial signatures and phenotypic roles.

Chronic insomnia (CI) is a complex disease involving multiple factors including genetics, gut microbiota, and brain structure and function. However, there lacks a unified framework to elucidate how these factors interact in CI. By combining data of clinical assessment, sleep behavior recording, cognitive test, multimodal MRI (structural, functional, and perfusion), gene, and gut microbiota, this study demonstrated that enhanced cerebral blood flow (CBF) similarities of the somatomotor network (SMN) acted as a key mediator to link multiple factors in CI. Specifically, we first demonstrated that only CBF but not morphological or functional networks exhibited alterations in patients with CI, characterized by increases within the SMN and between the SMN and higher-order associative networks. Moreover, these findings were highly reproducible and the CBF similarity method was test-retest reliable. Further, we showed that transcriptional profiles explained 60.4 % variance of the pattern of the increased CBF similarities with the most correlated genes enriched in regulation of cellular and protein localization and material transport, and gut microbiota explained 69.7 % inter-individual variance in the increased CBF similarities with the most contributions from Negativicutes and Lactobacillales. Finally, we found that the increased CBF similarities were correlated with clinical variables, accounted for sleep behaviors and cognitive deficits, and contributed the most to the patient-control classification (accuracy = 84.4 %). Altogether, our findings have important implications for understanding the neuropathology of CI and may inform ways of developing new therapeutic strategies for the disease.

Morphological Brain Networks of White Matter: Mapping, Evaluation, Characterization, and Application.

Although white matter (WM) accounts for nearly half of adult brain, its wiring diagram is largely unknown. Here, an approach is developed to construct WM networks by estimating interregional morphological similarity based on structural magnetic resonance imaging. It is found that morphological WM networks showed nontrivial topology, presented good-to-excellent test-retest reliability, accounted for phenotypic interindividual differences in cognition, and are under genetic control. Through integration with multimodal and multiscale data, it is further showed that morphological WM networks are able to predict the patterns of hamodynamic coherence, metabolic synchronization, gene co-expression, and chemoarchitectonic covariance, and associated with structural connectivity. Moreover, the prediction followed WM functional connectomic hierarchy for the hamodynamic coherence, is related to genes enriched in the forebrain neuron development and differentiation for the gene co-expression, and is associated with serotonergic system-related receptors and transporters for the chemoarchitectonic covariance. Finally, applying this approach to multiple sclerosis and neuromyelitis optica spectrum disorders, it is found that both diseases exhibited morphological dysconnectivity, which are correlated with clinical variables of patients and are able to diagnose and differentiate the diseases. Altogether, these findings indicate that morphological WM networks provide a reliable and biologically meaningful means to explore WM architecture in health and disease.

Learning metabolic dynamics from irregular observations by Bidirectional Time-Series State Transfer Network.

Modeling microbial metabolic dynamics is important for the rational optimization of both biosynthetic systems and industrial processes to facilitate green and efficient biomanufacturing. Classical approaches utilize explicit equation systems to represent metabolic networks, enabling the quantification of pathway fluxes to identify metabolic bottlenecks. However, these white-box models, despite their diverse applications, have limitations in simulating metabolic dynamics and are intrinsically inaccurate for industrial strains that lack information on network structures and kinetic parameters. On the other hand, black-box models do not rely on prior mechanistic knowledge of strains but are built upon observed time-series trajectories of biosynthetic systems in action. In practice, these observations are typically irregular, with discontinuously observed time points across multiple independent batches, each time point potentially containing missing measurements. Learning from such irregular data remains challenging for existing approaches. To address this issue, we present the Bidirectional Time-Series State Transfer Network (BTSTN) for modeling metabolic dynamics directly from irregular observations. Using evaluation data sets derived from both ideal dynamic systems and a real-world fermentation process, we demonstrate that BTSTN accurately reconstructs dynamic behaviors and predicts future trajectories. This approach exhibits enhanced robustness against missing measurements and noise, as compared to the state-of-the-art methods.IMPORTANCEIndustrial biosynthetic systems often involve strains with unclear genetic backgrounds, posing challenges in modeling their distinct metabolic dynamics. In such scenarios, white-box models, which commonly rely on inferred networks, are thereby of limited applicability and accuracy. In contrast, black-box models, such as statistical models and neural networks, are directly fitted or learned from observed time-series trajectories of biosynthetic systems in action. These methods typically assume regular observations without missing time points or measurements. If the observations are irregular, a pre-processing step becomes necessary to obtain a fully filled data set for subsequent model training, which, at the same time, inevitably introduces errors into the resulting models. BTSTN is a novel approach that natively learns from irregular observations. This distinctive feature makes it a unique addition to the current arsenal of technologies modeling metabolic dynamics.

Pressure-Induced Irreversible Metallization Accompanying Phase Transition of Chalcopyrite Cu(In0.7Ga0.3)Se2.

Chalcopyrite copper-indium-gallium diselenides (CIGS) have emerged as promising materials with remarkable electronic properties and potential applicability to high-efficiency solar cells. The crystal and electronic structures of CIGS can be continuously tuned from their initial states under pressure. Although pressure-induced band gap closure in CIGS has been predicted in extensive theoretical studies, it has not been supported by experimental evidence. Here, we comprehensively investigate the pressure-dependent optical, electronic, and structural properties of Cu(In0.7Ga0.3)Se2 up to 42.6 GPa. Our experimental results reveal an irreversible electronic transition from the semiconducting to the metallic state at 14.3 GPa. Under compression, the Cu(In0.7Ga0.3)Se2 structure evolves from a tetragonal I4̅2d phase to an orthorhombic Pna21 phase, which has not been previously reported in chalcopyrite. More intriguingly, the Pna21 phase is irreversible and possesses smaller Cu-Se and In/Ga-Se bond lengths and a smaller Cu-Se-Cu bond angle than the I4̅2d phase. Density functional theory calculations indicate a lower enthalpy of the Pna21 phase than that of the I4̅2d phase at pressures above 10.6 GPa. Meanwhile, density of states calculations illustrate that metallization arises from the overlap of the Se p and Cu d orbitals as the bond length reduces. This pressure-induced behavior could facilitate the development of novel devices with various phenomena involving strong coupling of the mechanical, electrical, and optical properties of chalcopyrite.

Serum Anion Gap at Admission Predicts All-Cause Mortality in Critically Ill Patients With Cirrhosis: A Retrospective Cohort Study.

INTRODUCTION: The primary objective of this study was to evaluate admission serum anion gap (AG) as a predictor of all-cause mortality in critically ill patients with cirrhosis. METHODS: A total of 3,084 cirrhotic patients were included and randomly divided into training and validation cohorts (n = 2,159 and 925, respectively). Patients were categorized into high and normal AG groups based on their AG values. Cox regression and Kaplan-Meier survival analysis were used to assess the relationships between AG levels and outcomes. RESULTS: Both cohorts showed strong parameter similarity ( P > 0.05). High AG was associated with significantly lower survival probabilities. Cox models confirmed elevated AG as a risk factor, even after adjusting for covariates (hazard ratio: 1.920, 1.793, and 1.764 for 30-day, 60-day, and hospital mortality, respectively). Subgroup analyses, especially regarding chronic kidney disease, revealed complex interactions. Serum AG displayed predictive power comparable with established scoring systems. DISCUSSION: Elevated AG at admission is a valuable predictor of poor outcomes and increased mortality risk in critically ill cirrhotic patients. Serum AG can serve as an easily accessible tool for risk assessment and prognosis evaluation in this population.

Semirecumbent Positioning During Anesthesia Recovery and Postoperative Hypoxemia: A Randomized Clinical Trial.

Importance: The efficacy of a semirecumbent position (SRP) in reducing postoperative hypoxemia during anesthesia emergence is unclear despite its widespread use. Objective: To determine the differences in postoperative hypoxemia between patients in an SRP and a supine position. Design, Setting, and Participants: This randomized clinical trial was performed at a tertiary hospital in China between March 20, 2021, and May 10, 2022. Patients scheduled to undergo laparoscopic upper abdominal surgery under general anesthesia were enrolled. Study recruitment and follow-up are complete. Interventions: Patients were randomized to 1 of the following positions at the end of the operation until leaving the postanesthesia care unit: supine (group S), 15° SRP (group F), or 30° SRP (group T). Main Outcomes and Measures: The primary outcome was the incidence of postoperative hypoxemia in the postanesthesia care unit. Severe hypoxemia was also evaluated. Results: Out of 700 patients (364 men [52.0%]; mean [SD] age, 47.8 [11.3] years), 233 were randomized to group S (126 men [54.1%]; mean [SD] age, 48.2 [10.9] years), 233 to group F (122 men [52.4%]; mean [SD] age, 48.1 [10.9] years), and 234 to group T (118 women [50.4%]; mean [SD] age, 47.2 [12.1] years). Postoperative hypoxemia differed significantly among the 3 groups (group S, 109 of 233 [46.8%]; group F, 105 of 233 [45.1%]; group T, 76 of 234 [32.5%]; P = .002). This difference was statistically significant for groups T vs S (risk ratio [RR], 0.69 [95% CI, 0.55-0.87]; P = .002) and groups T vs F (RR, 0.72 [95% CI, 0.57-0.91]; P = .007), but not for groups F vs S (RR, 0.96 [95% CI, 0.79-1.17]; P = .78). Severe hypoxemia also differed among the 3 groups (group S, 61 of 233 [26.2%]; group F, 53 of 233 [22.7%]; group T, 36 of 234 [15.4%]; P = .01). This difference was statistically significant for groups T vs S (RR, 0.59 [95% CI, 0.41-0.85]; P = .005). Conclusions and Relevance: In this randomized clinical trial of SRP during anesthesia recovery in patients undergoing laparoscopic upper abdominal surgery, postoperative hypoxemia was significantly reduced in group T compared with group F or group S. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100045087.

Development and reproduction of Scirtothrips dorsalis (Thysanoptera: Thripidae) on six host plant species.

Host plants can strongly influence the population performance of insects. Here, we investigated the development, survival, and oviposition of Scirtothrips dorsalis Hood on 6 host plants-Camellia sinensis ( L.) Kuntze (Ericales: Theaceae), Rosa chinensis Jacq. (Rosales: Rosaceae), Capsicum annuum L. (Solanales: Solanaceae), Eustoma grandiflorum (Hook.) G.Don (Gentianales: Gentianaceae), Glycine max (L.) Merr. (Fabales: Fabaceae), and Cucumis sativus L. (Cucurbitales: Cucurbitaceae), and constructed life tables for S. dorsalis on each plant. Significant differences in S. dorsalis development on the host species were observed. The mean developmental period from egg to adult was 11.45 ±â€…0.12 days, 11.24 ±â€…0.13 days, 12.08 ±â€…0.15 days, 12.28 ±â€…0.12 days, 12.67 ±â€…0.10 days, and 13.03 ±â€…0.11 days on C. sinensis, R. chinensis, C. annuum, E. grandiflorum, G. max, and C. sativus, respectively. Significant differences in survival of S. dorsalis were observed, namely, C. sinensis ≈ R. chinensis > E. grandiflorum ≈ C. annuum > G. max > C. sativus. The highest and lowest fecundities of S. dorsalis were recorded on R. chinensis (60.44 ±â€…1.53) and C. sativus (28.64 ±â€…1.02), respectively. Both of the net reproductive rate (R0) and intrinsic rate of increase (rm) of S. dorsalis were the highest on R. chinensis, with the values of 27.63 ±â€…0.58 and 0.142 ±â€…0.002, respectively; while the lowest on C. sativus, with the values of 8.81 ±â€…0.12 and 0.092 ±â€…0.003, respectively. Thus, R. chinensis was found to be the most suitable host, but C. sativus was the least suitable, for population development of S. dorsalis. Our results provide important information for the key control of S. dorsalis among different host plants.

A bioinspired heterostructured nanochannel based on dendrimer-gold network and aluminum oxide arrays for sensitive detection of miRNA.

BACKGROUND: MicroRNAs, as oncogenes or tumor suppressors, enable to up or down-regulate gene expression during tumorigenesis. The detection of miRNAs with high sensitivity is crucial for the early diagnosis of cancer. Inspired by biological ion channels, artificial nanochannels are considered as an excellent biosensing platform with relatively high sensitivity and stability. The current nanochannel biosensors are mainly based on homogeneous membranes, and their monotonous structure and functionality limit its further development. Therefore, it is necessary to develop a heterostructured nanochannel with high ionic current rectification to achieve highly sensitive miRNA detection. RESULTS: In this work, an asymmetric heterostructured nanochannel constructed from dendrimer-gold nanoparticles network and anodic aluminum oxide are designed through an interfacial super-assembly method, which can regulate ion transport and achieve sensitive detection of target miRNA. The symmetry breaking is demonstrated to endow the heterostructured nanochannels with an outstanding ionic current rectification performance. Arising from the change of surface charges in the nanochannels triggered by DNA cascade signal amplification in solution, the proposed heterogeneous nanochannels exhibits excellent DNA-regulated ionic current response. Relying on the nucleic acid's hybridization and configuration transformation, the target miRNA-122 associated with liver cancer can be indirectly quantified with a detection limit of 1 fM and a wide dynamic range from 1 fM to 10 pM. The correlation fitting coefficient R2 of the calibration curve can reach to 0.996. The experimental results show that the method has a good recovery rate (98%-105 %) in synthetic samples. SIGNIFICANCE: This study reveals how the surface charge density of nanochannels regulate the ionic current response in the heterostructured nanochannels. The designed heterogeneous nanochannels not only possess high ionic current rectification property, but also enable to induce superior transport performance by the variation of surface chemistry. The proposed biosensor is promising for applications in early diagnosis of cancers, life science research, and single-entity electrochemical detection.

Inhibition of ACOX1 enhances the therapeutic efficacy of obeticholic acid in treating non-alcoholic fatty liver disease and mitigates its lipotoxicity.

Background and aims: High-dose Obeticholic acid exhibits promise for non-alcoholic fatty liver disease (NAFLD) treatment but can induce lipotoxicity. Our study sought to understand this mechanism and propose a solution. Approach and Results: In a non-alcoholic fatty liver disease (NAFLD) model induced by a high-fat diet in FXR-/- mice, we pinpointed that FXR regulated the expression of ACOX1 through RNA-Seq analysis. In the livers of FXR-/- mice, both ACOX1 mRNA and protein expression notably decreased. In both HL-7702 and HEP-G2 cells, the silencing of FXR through shRNA plasmids decreased ACOX1 expression, while FXR activation with GW4064 increased it. These effects were reversible with the ACOX1-specific inhibitor, 10,12-Tricosadiynoic acid. In the NAFLD model of FXR-/- mice, The activation of ACOX1 is correlated with elevated serum LDL, triglycerides, and aggravated hepatic steatosis. However, the combination of 10,12-Tricosadiynoic acid with low-dose obeticholic acid effectively treated hepatic steatosis, reducing LDL levels in the NAFLD model of wild-type mice. This combination therapy demonstrated efficacy comparable to high-dose obeticholic acid alone. Notably, the combined drug regimen treats hepatic steatosis by inhibiting the IL-1ß and α-SMA pathways in NAFLD. Conclusion: Combining ACOX1-specific inhibitors with low-dose obeticholic acid effectively treats high-fat diet-induced hepatic steatosis and reduces serum LDL. This approach enhances the therapeutic effects of obeticholic acid and mitigates its lipotoxicity by inhibiting the IL-1ß and α-SMA pathways.