Enhanced SLC35B2/SAV1 sulfation axis promotes tumor growth by inhibiting Hippo signaling in HCC.

BACKGROUND AND AIMS: Protein tyrosine sulfation (PTS) is a common posttranslational modification that regulates a variety of physiological and pathological processes. However, the role of PTS in cancer remains poorly understood. The goal of this study was to determine whether and how PTS plays a role in HCC progression. APPROACH AND RESULTS: By mass spectrometry and bioinformatics analysis, we identified SAV1 as a novel substrate of PTS in HCC. Oxidative stress upregulates the transcription of SLC35B2, a Golgi-resident transporter of sulfate donor 3'-phosphoadenosine 5'-phosphosulfate, leading to increased sulfation of SAV1. Sulfation of SAV1 disrupts the formation of the SAV1-MST1 complex, resulting in a decrease of MST1 phosphorylation and subsequent inactivation of Hippo signaling. These molecular events ultimately foster the growth of HCC cells both in vivo and in vitro. Moreover, SLC35B2 is a novel transcription target gene of the Hippo pathway, constituting a positive feedback loop that facilitates HCC progression under oxidative stress. CONCLUSIONS: Our findings reveal a regulatory mechanism of the SLC35B2/SAV1 sulfation axis in response to oxidative stress, highlighting its potential as a promising therapeutic target for HCC.

Genome-wide identification and characterization of NAC transcription factor family members in Trifolium pratense and expression analysis under lead stress.

BACKGROUND: The NAC TF family is widely involved in plant responses to various types of stress. Red clover (Trifolium pratense) is a high-quality legume, and the study of NAC genes in red clover has not been comprehensive. The aim of this study was to analyze the NAC gene family of red clover at the whole-genome level and explore its potential role in the Pb stress response. RESULTS: In this study, 72 TpNAC genes were identified from red clover; collinearity analysis showed that there were 5 pairs of large fragment replicators of TpNAC genes, and red clover was found to be closely related to Medicago truncatula. Interestingly, the TpNAC genes have more homologs in Arabidopsis thaliana than in soybean (Glycine max). There are many elements in the TpNAC genes promoters that respond to stress. Gene expression analysis showed that all the TpNAC genes responded to Pb stress. qRT-PCR showed that the expression levels of TpNAC29 and TpNAC42 were significantly decreased after Pb stress. Protein interaction network analysis showed that 21 TpNACs and 23 other genes participated in the interaction. In addition, the TpNAC proteins had three possible 3D structures, and the secondary structure of these proteins were mainly of other types. These results indicated that most TpNAC members were involved in the regulation of Pb stress in red clover. CONCLUSION: These results suggest that most TpNAC members are involved in the regulation of Pb stress in red clover. TpNAC members play an important role in the response of red clover to Pb stress.

Toward the Next Generation Human-Machine Interaction: Headworn Wearable Devices.

Wearable devices are lightweight and portable devices worn directly on the body or integrated into the user's clothing or accessories. They are usually connected to the Internet and combined with various software applications to monitor the user's physical conditions. The latest research shows that wearable head devices, particularly those incorporating microfluidic technology, enable the monitoring of bodily fluids and physiological states. Here, we summarize the main forms, functions, and applications of head wearable devices through innovative researches in recent years. The main functions of wearable head devices are sensor monitoring, diagnosis, and even therapeutic interventions. Through this application, real-time monitoring of human physiological conditions and noninvasive treatment can be realized. Furthermore, microfluidics can realize real-time monitoring of body fluids and skin interstitial fluid, which is highly significant in medical diagnosis and has broad medical application prospects. However, despite the progress made, significant challenges persist in the integration of microfluidics into wearable devices at the current technological level. Herein, we focus on summarizing the cutting-edge applications of microfluidic contact lenses and offer insights into the burgeoning intersection between microfluidics and head-worn wearables, providing a glimpse into their future prospects.

Identification of a new gene signature for prognostic evaluation in cervical cancer: based on cuproptosis-associated angiogenesis and multi-omics analysis.

Patients with recurrent or metastatic cervical cancer are in urgent need of novel prognosis assessment or treatment approaches. In this study, a novel prognostic gene signature was discovered by utilizing cuproptosis-related angiogenesis (CuRA) gene scores obtained through weighted gene co-expression network analysis (WGCNA) of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. To enhance its reliability, the gene signature was refined by integrating supplementary clinical variables and subjected to cross-validation. Meanwhile, the activation of the VEGF pathway was inferred from an analysis of cell-to-cell communication, based on the expression of ligands and receptors in cell transcriptomic datasets. High-CuRA patients had less infiltration of CD8 + T cells and reduced expression of most of immune checkpoint genes, which indicated greater difficulty in immunotherapy. Lower IC50 values of imatinib, pazopanib, and sorafenib in the high-CuRA group revealed the potential value of these drugs. Finally, we verified an independent prognostic gene SFT2D1 was highly expressed in cervical cancer and positively correlated with the microvascular density. Knockdown of SFT2D1 significantly inhibited ability of the proliferation, migration, and invasive in cervical cancer cells. CuRA gene signature provided valuable insights into the prediction of prognosis and immune microenvironment of cervical cancer, which could help develop new strategies for individualized precision therapy for cervical cancer patients.

CCT251545 enhances drug delivery and potentiates chemotherapy in multidrug-resistant cancers by Rac1-mediated macropinocytosis.

It was well known that P-glycoprotein (P-gp/ABCB1) is a master regulator of multidrug resistance (MDR) in cancers. However, the clinical benefit from blocking this pathway remains inconclusive, which motivates a paradigm shift towards alternative strategies for enhancing drug influx. Using a patient-derived organoid (PDO)-based drug screening platform, we report that the combined use of chemotherapy and CCT251545 (CCT) displays robust synergistic effect against PDOs and reduces proliferation of MDR cancer cells in vitro, and results in regression of xenograft tumors, reductions in metastatic dissemination and recurrence rate in vivo. The synergistic activity mediated by CCT can be mainly attributed to the intense uptake of chemotherapeutic agents into the cells, accompanied by alterations in cell phenotypes defined as a mesenchymal epithelial transformation (MET). Mechanistically, analysis of the transcriptome coupled with validation in cellular and animal models demonstrate that the chemosensitizing effect of CCT is profoundly affected by Rac1-dependent macropinocytosis. Furthermore, CCT binds to NAMPT directly, resulting in elevated NAD levels within MDR cancer cells. This effect promotes the assembly of adherents junction (AJ) components with cytoskeleton, which is required for continuous induction of macropinocytosis and consequent drug internalization. Overall, our results illustrate the potential use of CCT as a combination partner for the commonly used chemotherapeutic drugs in the management of MDR cancers.

The Impact of high-performance work system perceived by medical staff on job satisfaction: the mediating role of self-efficacy.

As the mainstay of healthcare, the job satisfaction of medical staff deserves attention. This study aimed to explore the correlation between the perception of the high-performance work system (P-HPWS) and job satisfaction of medical staff in public hospitals and to further investigate the mediating effect of self-efficacy. From November 2019 to January 2020, a cross-sectional survey on working doctors and nurses was conducted in five tertiary public hospitals in China. A total of 520 participants were surveyed. The P-HPWS, job satisfaction, and self-efficacy were assessed using the 25-item self-administered scale, six-item job satisfaction questionnaire, and the General Self-Efficacy Scale, respectively. Linear regression and mediation effects models were used to identify the associations between primary variables. The results showed a significant positive correlation between P-HPWS and job satisfaction (P < 0.01), while self-efficacy played a mediating role between P-HPWS and job satisfaction. This finding reveals the benefits of improving employees' P-HPWS and self-efficacy on their job satisfaction, and that hospitals can improve their management systems by implementing and refining HPWS.

Targeting Metabolic-Redox Circuits for Cancer Therapy.

Metabolic alterations and elevated levels of reactive oxygen species (ROS) are two characteristics of cancer. The metabolic patterns of cancer cells are elaborately reprogrammed to fulfill the high biomass demands of rapid propagation. ROS, the byproducts of metabolic processes, are accumulated in cancer cells partially due to metabolic abnormalities or oncogenic mutations. To prevent oxidative damage, cancer cells can orchestrate metabolic adaptation to maintain reduction-oxidation (redox) balance by producing reducing equivalents. ROS, acting as second messengers, can in turn manipulate metabolic pathways by directly or indirectly affecting the function of metabolic enzymes. In this review we discuss how cancer cell metabolism and redox signaling are intertwined, with an emphasis on the perspective of targeting metabolic-redox circuits for cancer therapy.

Enhanced Interfacial Charge Transfer/Separation By LSPR-Induced Defective Semiconductor Toward High Co2 RR Performance.

Solar-driven reduction of CO2 emissions into high-value-added carbonaceous compounds has been recognized as a sustainable energy conversion way. The high-efficiency charge separation and effective activation are the critical issues in the process. The local plasma effect of metal and the vacancy of semiconductors in the metal-semiconductor heterostructure can solve this issue extensively. Herein, an oxygen vacancy photocatalyst containing uniform Ag nanoparticles (Ag-20@Nb2 O5- x ) is designed, which exhibits an excellent reduction performance and the CO yield can reach 59.13 µmol g-1 with high selectivity. The carrier migration is accelerated and the activation of CO2 is facilitated by the local surface plasmon effect and oxygen vacancy. Moreover, the photocatalytic CO2 reduction mechanism is revealed based on the density functional theory and in situ technology in detail. This work provides an in-depth understanding of the design of more ingenious metal-semiconductor photocatalysts to achieve more efficient charge transfer.

Brain-Targeted HFn-Cu-REGO Nanoplatform for Site-Specific Delivery and Manipulation of Autophagy and Cuproptosis in Glioblastoma.

Durable glioblastoma multiforme (GBM) management requires long-term chemotherapy after surgery to eliminate remaining cancerous tissues. Among chemotherapeutics, temozolomide is considered as the first-line drug for GBM therapy, but the treatment outcome is not satisfactory. Notably, regorafenib, an oral multi-kinase inhibitor, has been reported to exert a markedly superior effect on GBM suppression compared with temozolomide. However, poor site-specific delivery and bioavailability significantly restrict the efficient permeability of regorafenib to brain lesions and compromise its treatment efficacy. Therefore, human H-ferritin (HFn), regorafenib, and Cu2+ are rationally designed as a brain-targeted nanoplatform (HFn-Cu-REGO NPs), fulfilling the task of site-specific delivery and manipulating autophagy and cuproptosis against GBM. Herein, HFn affords a preferential accumulation capacity to GBM due to transferrin receptor 1 (TfR1)-mediated active targeting and pH-responsive delivery behavior. Moreover, regorafenib can inhibit autophagosome-lysosome fusion, resulting in lethal autophagy arrest in GBM cells. Furthermore, Cu2+ not only facilitates the encapsulation of regorafenib to HFn through coordination interaction but also disturbs copper homeostasis for triggering cuproptosis, resulting in a synergistical effect with regorafenib-mediated lethal autophagy arrest against GBM. Therefore, this work may broaden the clinical application scope of Cu2+ and regorafenib in GBM treatment via modulating autophagy and cuproptosis.

Rapid Detection of Extensive Drug Resistance by Xpert MTB/XDR Optimizes Therapeutic Decision-Making in Rifampin-Resistant Tuberculosis Patients.

The Xpert MTB/XDR assay met the critical need for etiologic diagnosis of tuberculosis and rifampin resistance in previous studies. However, its benefits in tailoring the treatment regimen and improving the outcome for patients with rifampin-resistant tuberculosis (RR-TB) require further investigation. In this study, the Xpert MTB/XDR assay was used to determine the resistance profile of second-line drugs for RR-TB patients in two registered multicenter clinical trials, TB-TRUST (NCT03867136) and TB-TRUST-plus (NCT04717908), with the aim of testing the efficacy of all-oral shorter regimens in RR-TB patients in China. Patients would receive the fluoroquinolone-based all-oral shorter regimen, the injectable-containing regimen, or the bedaquiline-based regimen depending on fluoroquinolone susceptibility by using Xpert MTB/XDR. Among the 497 patients performed with Xpert MTB/XDR, 128 (25.8%) had infections resistant to fluoroquinolones and/or second-line injectable drugs (SLIDs). A total of 371 participants were recruited for the trials, and whole-genome sequencing (WGS) was performed on all corresponding culture-positive baseline strains. Taking the WGS results as the standard, the accuracy of the Xpert MTB/XDR assay in terms of resistance detection was 95.2% to 99.0% for all drugs. A total of 33 cases had inconsistent results, 9 of which were due to resistance heterogeneity. Most of the patients (241/281, 85.8%) had sputum culture conversion at 2 months. In conclusion, the Xpert MTB/XDR assay has the potential to serve as a quick reflex test in patients with RR-TB, as detected via Xpert MTB/RIF, to provide a reliable drug susceptibility profile of the infecting Mycobacterium tuberculosis strain and to initiate optimized treatment promptly.

High Myopia Normative Database of Peripapillary Retinal Nerve Fiber Layer Thickness to Detect Myopic Glaucoma in a Chinese Population.

PURPOSE: To develop and validate the performance of a high myopia (HM)-specific normative database of peripapillary retinal nerve fiber layer (pRNFL) thickness in differentiating HM from highly myopic glaucoma (HMG). DESIGN: Cross-sectional multicenter study. PARTICIPANTS: A total of 1367 Chinese participants (2325 eyes) with nonpathologic HM or HMG were included from 4 centers. After quality control, 1108 eyes from 694 participants with HM were included in the normative database; 459 eyes from 408 participants (323 eyes with HM and 136 eyes with HMG) and 322 eyes from 197 participants (131 eyes with HM and 191 eyes with HMG) were included in the internal and external validation sets, respectively. Only HMG eyes with an intraocular pressure > 21 mmHg were included. METHODS: The pRNFL thickness was measured with swept-source (SS) OCT. Four strategies of pRNFL-specified values were examined, including global and quadrantic pRNFL thickness below the lowest fifth or the lowest first percentile of the normative database. MAIN OUTCOMES MEASURES: The accuracy, sensitivity, and specificity of the HM-specific normative database for detecting HMG. RESULTS: Setting the fifth percentile of the global pRNFL thickness as the threshold, using the HM-specific normative database, we achieved an accuracy of 0.93 (95% confidence interval [CI], 0.90-0.95) and 0.85 (95% CI, 0.81-0.89), and, using the first percentile as the threshold, we acheived an accuracy of 0.85 (95% CI, 0.81-0.88) and 0.70 (95% CI, 0.65-0.75) in detecting HMG in the internal and external validation sets, respectively. The fifth percentile of the global pRNFL thickness achieved high sensitivities of 0.75 (95% CI, 0.67-0.82) and 0.75 (95% CI, 0.68-0.81) and specificities of 1.00 (95% CI, 0.99-1.00) and 1.00 (95% CI, 0.97-1.00) in the internal and external validation datasets, respectively. Compared with the built-in database of the OCT device, the HM-specific normative database showed a higher sensitivity and specificity than the corresponding pRNFL thickness below the fifth or first percentile (P < 0.001 for all). CONCLUSIONS: The HM-specific normative database is more capable of detecting HMG eyes than the SS OCT built-in database, which may be an effective tool for differential diagnosis between HMG and HM. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Establishment and Clinical Application in Stroke of a Serum Copeptin Time-Resolved Fluorescence Immunoassay.

The serum biomarker copeptin, an innovative and stable substitute biomarker of vasopressin, is associated with stroke. Therefore, establishing a highly sensitive time-resolved fluorescence immunoassay for copeptin (copeptin-TRFIA) is helpful to measure stroke and evaluate its value in clinical applications. Double antibody sandwich was used to establish copeptin-TRFIA. The established method was then assessed. Two coated and Eu3+-labeled copeptin monoclonal specific antibodies targeting different antigen epitopes were employed. The serum fluorescence counts of patients with stroke and healthy volunteers were detected by using the well-established copeptin-TRFIA. Serum copeptin levels were measured and analyzed statistically. The actual measurement linearity range of the proposed method was 0.13-44.66 ng/mL. Copeptin-TRFIA had the inter-assay coefficient of variation (CV) of 6.49%-9.08% and the intra-assay CV of 4.75%-7.77%. Patients with cerebral infarction (CI) and intracerebral hemorrhage (ICH) had significantly higher serum copeptin levels than healthy subjects. Copeptin concentrations in the serum of patients with stroke were significantly correlated with the scores of the National Institute for Healthy Stroke Scale (NIHSS) and modified Rankin Scale (mRS). A highly sensitive copeptin-TRFIA was successfully established. Serum copeptin has a certain value in the clinical diagnosis and prognosis of stroke.

Transition from semiconductor to conductor of a Mg2N electride induced by strain.

Electrides are a class of materials in which electrons are not bound to atoms but are similar to anions in crystals. To date, there are more than 300 electrides that have been discovered by first-principles. Alkaline-earth metal nitrides (AE2N, AE = Be, Mg, Ca, Sr, and Ba) are an important component of electride materials. Ca2N, Sr2N, and Ba2N structures have been identified and synthesized in previous research studies. Furthermore, the structures of Be2N (R3̄m symmetry) and Mg2N (R3m symmetry) were recently identified. For Mg2N, it has zero-dimension (0D) interstitial localized electrons and band structure with semiconductor properties, which is significantly different from the other AE2N structures (two-dimension electrides and metal properties). Consequently, Mg2N was systematically studied in this work. We found that the pristine Mg2N was an indirect band gap semiconductor with a band gap of 0.243 eV. It transitioned to a metal when 2% stretch stress was applied to the c-axis. Moreover, at 5% stretch stress, the structure exhibited 2D interstitial localized electrons with the superconducting transition temperature (Tc) of 0.3 K. These studies thus provide a deeper understanding of the physicochemical properties of Mg2N as an electride.

Non-Pharmacological Interventions in Patients With Heart Failure With Reduced Ejection Fraction: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: To determine the effectiveness of non-pharmacologic interventions and the additional benefits of their combination in patients with heart failure with reduced ejection fraction (HFrEF). DATA SOURCES: We searched PubMed, Embase, and the Cochrane Clinical Trials Register from the date of database inception to April 22, 2023. STUDY SELECTION: Randomized controlled trials involving non-pharmacologic interventions conducted in patients with HFrEF were included. DATA EXTRACTION: Data were extracted by 2 independent reviewers based on a pre-tested data extraction form. The quality of evidence was assessed using the Cochrane Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation method. DATA SYNTHESIS: A total of 82 eligible studies (4574 participants) were included. We performed a random-effects model within a Bayesian framework to calculate weighted mean differences (WMDs) and 95% credibility intervals. High or moderate certainty evidence indicated that high-intensity aerobic interval training (HIAIT) was best on improving 6-minute walk distance (6MWD; 68.55 m [36.41, 100.47]) and left ventricular ejection fraction (6.28% [3.88, 8.77]), while high-intensity aerobic continuous training (HIACT) is best on improving peak oxygen consumption (Peak VO2; 3.48 mL/kg•min [2.84, 4.12]), quality of life (QOL; -17.26 [-29.99, -7.80]), resting heart rate (-8.20 bpm [-13.32, -3.05]), and N-terminal pro-B-type natriuretic peptide (-600.96 pg/mL [-902.93, -404.52]). Moderate certainty evidence supported the effectiveness of inspiratory muscle training to improve peak oxygen consumption and functional electrical stimulation to improve QOL. Moderate-intensity aerobic continuous training (MIACT) plus moderate-intensity resistance training (MIRT) had additional benefits in Peak VO2, 6MWD, and QOL. This review did not provide a comprehensive evaluation of adverse events. CONCLUSIONS: Both HIAIT and HIACT are the most effective single non-pharmacologic interventions for HFrEF. MIACT plus MIRT had additional benefits in improving peak oxygen consumption, 6MWD, and QOL.

Identification and Evolutionary Analysis of the Auxin Response Factor (ARF) Family Based on Transcriptome Data from Caucasian Clover and Analysis of Expression Responses to Hormones.

Caucasian clover (Trifolium ambiguum M. Bieb.) is an excellent perennial plant in the legume family Fabaceae, with a well-developed rhizome and strong clonal growth. Auxin is one of the most important phytohormones in plants and plays an important role in plant growth and development. Auxin response factor (ARF) can regulate the expression of auxin-responsive genes, thus participating in multiple pathways of auxin transduction signaling in a synergistic manner. No genomic database has been established for Caucasian clover. In this study, 71 TaARF genes were identified through a transcriptomic database of Caucasian clover rhizome development. Phylogenetic analysis grouped the TaARFs into six (1-6) clades. Thirty TaARFs contained a complete ARF structure, including three relatively conserved regions. Physical and chemical property analysis revealed that TaARFs are unstable and hydrophilic proteins. We also analyzed the expression pattern of TaARFs in different tissues (taproot, horizontal rhizome, swelling of taproot, rhizome bud and rhizome bud tip). Quantitative real-time RT-PCR revealed that all TaARFs were responsive to phytohormones (indole-3-acetic acid, gibberellic acid, abscisic acid and methyl jasmonate) in roots, stems and leaves. These results helped elucidate the role of ARFs in responses to different hormone treatments in Caucasian clover.

Hypoxia-induced lncRNA STEAP3-AS1 activates Wnt/ß-catenin signaling to promote colorectal cancer progression by preventing m6A-mediated degradation of STEAP3 mRNA.

BACKGROUND: Hypoxia, a typical hallmark of solid tumors, exhibits an essential role in the progression of colorectal cancer (CRC), in which the dysregulation of long non-coding RNAs (lncRNAs) is frequently observed. However, the underlying mechanisms are not clearly defined. METHODS: The TCGA database was analyzed to identify differential lncRNA expression involved in hypoxia-induced CRC progression. qRT-PCR was conducted to validate the upregulation of lncRNA STEAP3-AS1 in CRC cell lines and tumor-bearing mouse and zebrafish models under hypoxia. ChIP-qRT-PCR was used to detect the transcriptional activation of STEAP3-AS1 mediated by HIF-1α. RNA-seq, fluorescent in situ hybridization, RNA pulldown, RNA immunoprecipitation, co-immunoprecipitation, immunofluorescence and immunoblot experiments were used to ascertain the involved mechanisms. Functional assays were performed in both in vitro and in vivo models to investigate the regulatory role of STEAP3-AS1/STEAP3/Wnt/ß-catenin axis in CRC proliferation and metastasis. RESULTS: Here, we identified a hypoxia-induced antisense lncRNA STEAP3-AS1 that was highly expressed in clinical CRC tissues and positively correlated with poor prognosis of CRC patients. Upregulation of lncRNA STEAP3-AS1, which was induced by HIF-1α-mediated transcriptional activation, facilitated the proliferation and metastasis of CRC cells both in vitro and in vivo. Mechanistically, STEAP3-AS1 interacted competitively with the YTH domain-containing family protein 2 (YTHDF2), a N6-methyladenosine (m6A) reader, leading to the disassociation of YTHDF2 with STEAP3 mRNA. This effect protected STEAP3 mRNA from m6A-mediated degradation, enabling the high expression of STEAP3 protein and subsequent production of cellular ferrous iron (Fe2+). Increased Fe2+ levels elevated Ser 9 phosphorylation of glycogen synthase kinase 3 beta (GSK3ß) and inhibited its kinase activity, thus releasing ß-catenin for nuclear translocation and subsequent activation of Wnt signaling to support CRC progression. CONCLUSIONS: Taken together, our study highlights the mechanisms of lncRNA STEAP3-AS1 in facilitating CRC progression involving the STEAP3-AS1/STEAP3/Wnt/ß-catenin axis, which may provide novel diagnostic biomarkers or therapeutic targets to benefit CRC treatment. Hypoxia-induced HIF-1α transcriptionally upregulates the expression of lncRNA STEAP3-AS1, which interacts competitively with YTHDF2, thus upregulating mRNA stability of STEAP3 and consequent STEAP3 protein expression. The enhanced STEAP3 expression results in production of cellular ferrous iron (Fe2+), which induces the Ser 9 phosphorylation and inactivation of GSK3ß, releasing ß-catenin for nuclear translocation and contributing to subsequent activation of Wnt signaling to promote CRC progression.

Tunable Schottky and ohmic contacts in the Ti2NF2/α-Te van der Waals heterostructure.

Two dimensional α-Te holds great promise in optoelectronic devices because of its high mobility and excellent environmental stability. In this study, the electronic structures and interfacial contact characteristics of the Ti2NF2/α-Te van der Waals heterostructure are investigated by means of first-principles calculations. It is found that p-type Schottky contacts with a Schottky barrier (SB) of 0.21 eV are formed at the Ti2NF2/α-Te interface. By applying external electric fields or controlling the interlayer coupling between the Ti2NF2 and α-Te monolayers, the SB height can be effectively tuned, and all the n-type Schottky, p-type Schottky, n-type ohmic and p-type ohmic contacts can be achieved. Such an extremely high tunability is further found to be closely associated with the charge transfer at the interface, as well as the interface dipole and the potential step. Our results provide an avenue for the design of future α-Te-based electronic devices with high performance.

Surgesture: a novel instrument based on surgical actions for objective skill assessment.

BACKGROUND: Due to varied surgical skills and the lack of an efficient rating system, we developed Surgesture based on elementary functional surgical gestures performed by surgeons, which could serve as objective metrics to evaluate surgical performance in laparoscopic cholecystectomy (LC). METHODS: We defined 14 LC basic Surgestures. Four surgeons annotated Surgestures among LC videos performed by experts and novices. The counts, durations, average action time, and dissection/exposure ratio (D/E ratio) of LC Surgestures were compared. The phase of mobilizing hepatocystic triangle (MHT) was extracted for skill assessment by three professors using a modified Global Operative Assessment of Laparoscopic Skills (mGOALS). RESULTS: The novice operation time was significantly longer than the expert operation time (58.12 ± 19.23 min vs. 26.66 ± 8.00 min, P < 0.001), particularly during MHT phase. Novices had significantly more Surgestures than experts in both hands (P < 0.05). The left hand and inefficient Surgesture of novices were dramatically more than those of experts (P < 0.05). The experts demonstrated a significantly higher D/E ratio of duration than novices (0.79 ± 0.37 vs. 2.84 ± 1.98, P < 0.001). The counts and time pattern map of LC Surgestures during MHT demonstrated that novices tended to complete LC with more types of Surgestures and spent more time exposing the surgical scene. The performance metrics of LC Surgesture had significant but weak associations with each aspect of mGOALS. CONCLUSION: The newly constructed Surgestures could serve as accessible and quantifiable metrics for demonstrating the operative pattern and distinguishing surgeons with various skills. The association between Surgestures and Global Rating Scale laid the foundation for establishing a bridge to automated objective surgical skill evaluation.

Longitudinal white matter hyperintensity changes and cognitive decline in patients with minor stroke.

BACKGROUND AND OBJECTIVE: As reported, both minor stroke and white matter hyperintensities (WMHs) are associated with an increased risk of cognitive impairment and dementia. The underlying factors for dynamic changes in WMH volume and cognitive performances in patients with minor stroke remain poorly understood. A 2-year longitudinal study was designed to investigate the factors associated with the changes in white matter hyperintensity (WMH) volume on brain MRI and cognitive decline in patients with minor stroke. METHODS: A group of eligible patients with minor ischemic stroke was recruited in a row. At the initial and 2-year follow-up visits, all the participants underwent routine examinations, multimodal MRI, and cognitive assessment. Using a lesion prediction algorithm tool, we were able to automate the measurement of the change in WMH volume. During the 2-year follow-up, cognitive function was evaluated using Telephone Interview for Cognitive Status-Modified (TICS-m). Participants' demographic, clinical, and therapeutic data were collected and statistically analyzed. Regression analyses were used to test the relationships between risk factors and changes in WMH volume and cognitive decline. RESULTS: Finally, we followed up with 225/261 participants for 2 years, with a mean age of 65.67 ± 10.73 years (65.6% men). WMH volume was observed to be increased in 113 patients, decreased in 74 patients, and remained stable in 58 patients. Patients with WMH progression were more often had a history of hypertension (p = 0.006) and a higher CSVD burden both at baseline and follow-up visit (p < 0.05). Longitudinally, the proportion of patients taking antihypertension medications on a regular basis in the regression group was higher than in the stable group (p = 0.01). When compared to the stable group, the presence of lacunes (OR 9.931, 95% CI 1.597-61.77, p = 0.014) was a stronger predictor of progression in WMH volume. 87 subjects (38.6%) displayed incident cognitive impairment. The progression of WMH volume was a significant risk factor for cognitive decline (p < 0.001). CONCLUSIONS: The longitudinal change of WMH is dynamic. The regressive WMH volume was associated with the use of antihypertensive medications on a regular basis. The presence of lacunes at the initial visit of the study was a stronger predictor of WMH progression. The progression of WMH volume could be useful in predicting cognitive decline in patients with minor stroke.

Cecropin-Loaded Zeolitic Imidazolate Framework Nanoparticles with High Biocompatibility and Cervical Cancer Cell Toxicity.

Cecropins (CECs) are insect venom-derived amphiphilic peptides with numerous pharmacological effects, including anti-inflammatory, antibacterial, antiviral, and anti-tumor activities. Cecropins induce tumor cell death by disrupting phospholipid membrane integrity. However, non-specific cytotoxicity and in vivo rapid degradation limit clinical application. Nanotechnologies provide novel strategies for tumor eradication, including nanocarriers that can precisely target drugs to tumor tissue. We report the fabrication of CEC-encapsulated zeolitic imidazolate framework 8 (ZIF-8) nanoparticles (CEC@ZIF-8 NPs) via the preparation of CEC@ZIF-8 NPs in pure water by one-pot stirring. This method yielded morphologically uniform NPs with 20 wt% drug loading capacity and 9% loading efficiency. The NP formulation protected CECs from proteasome degradation, enhanced peptide bioavailability, promoted HeLa tumor cell uptake, and increased antitumor efficacy compared to free CECs. In conclusion, this ZIF-8 encapsulation strategy may enhance the clinical applicability of CECs and other antitumor peptides.