Coupling Effect of Structural Lubrication and Thermal Excitation on Phononic Friction.

This work investigates the coupling effect of structural lubrication and thermal excitation on phononic friction between black phosphorus (BP) layers. As the rotation angle increases from commensurate to incommensurate states, the friction gradually decreases at any temperature. However, the role of temperature in friction depends on commensurability. For a rotation angle less than 10°, increasing temperature leads to a decrease in friction due to thermal excitation. Conversely, when the rotation angle exceeds 10°, elevated temperature results in an increase in friction due to the effect of thermal collision. At a critical rotation angle of 10°, higher temperatures lead to reduced friction through thermal lubrication at low speeds, and at large speeds, the thermal excitation duration becomes so short that the role of thermal lubrication is weakened, and instead thermal collision dominates. Further research reveals that BP's ability to withstand different maximum speeds is also determined by commensurability. Finally, a method to measure the sliding period length of a rotated tip through an unrotated substrate potential energy topography is proposed and simply verified by using the phonon spectrum.

Phonon energy dissipation in friction between black phosphorus layers.

Herein, we employ molecular dynamics simulations to decode the friction properties and phonon energy dissipation between black phosphorus layers. The observations reveal the influence of three factors, temperature, velocity, and normal load, on the friction force of monolayer/bilayer black phosphorus. Specifically, friction is negatively correlated with layer thickness and temperature, and positively correlated with velocity and normal load. The change in friction force is further explained in terms of frictional energy dissipation, and supplemented by the height of potential barriers as well as the number of excited phonons. From the phonon spectrum analysis, the phonon number at the contact interface is found to be higher than that at the non-contact interface. This is due to the larger distance of the contact interface atoms deviate from their equilibrium positions, resulting in higher total energy generated by more intense oscillations, and therefore contributes greater to friction.

Feasibility of Ultrasound-Guided Percutaneous Axillary Artery Cannulation for Veno-Arterial Extracorporeal Membrane Oxygenation and its Effect on the Recovery of Spontaneous Heartbeat in Patients with ECPR.

Objective: The measurement of the right and left axillary arteries and aortic arch and their vessels by multi-row spiral CT angiography provides the basis for clinical catheter selection and depth for axillary artery placement. This study reported the clinical experience of 7 patients who successfully underwent ultrasound-guided percutaneous axillary artery cannulation for veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods: Patients who had CT angiography of the thoracic aorta at our institution between January 2020 and March 2022 were assessed for eligibility and included. The diameters of the cephalic trunk (D1), right common carotid artery (D2), right axillary artery (D3), left common carotid artery (D4), left axillary artery opening (D5), right axillary artery cannulation length (L1), and left axillary artery cannulation length (L2) were measured. The tangential angles α, ß, and γ of the cephalic trunk, left common carotid artery and left subclavian and aorta was measured using an automatic angle-forming tool. The decision to use a 15F cannula for ultrasound-guided percutaneous axillary artery cannulation in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) aims to achieve optimal vascular access. This cannula size strikes a balance, providing sufficient blood flow rates for ECMO support while minimizing the risk of complications associated with larger cannulas. Precise measurements of arterial dimensions, including the cephalic trunk, common carotid arteries, and axillary arteries, play a crucial role in guiding catheter selection and determining the depth of axillary artery placement. These measurements allow for tailored approaches based on individual patient characteristics, enhancing the safety and efficacy of the intervention. Additionally, measuring tangential angles (α, ß, and γ) provides insights into arterial alignment, optimizing the cannula trajectory for efficient blood flow. The use of an automatic angle-forming tool enhances measurement precision, contributing to procedural accuracy, minimizing complications, and ensuring the success of ultrasound-guided percutaneous axillary artery cannulation. In summary, the choice of a 15F cannula and precise measurements are essential components of the methodology, emphasizing safety, efficacy, and personalized approaches in VA-ECMO. From March to June 2022, 7 patients (6 males and 1 female) in our intensive care medicine department underwent successful ultrasound-guided percutaneous axillary artery cannulation for VA-ECMO with 15F cannula, including 3 cases with extracorporeal cardiopulmonary resuscitation (ECPR) and 4 cases with circulatory collapse. Results: 292 patients met the study criteria, 215 males and 77 females, with a mean age of 67.2±14.2 years. The measurements showed that D1 was (13.1±2.0) mm, D2 was (8.8±2.5) mm, D3 was (6.1±1.2) mm, D4 was (8.3±3.5) mm, D5 was (6.1±1.1) mm, L1 was (114.1±17.8) mm, and L2 was (128.4±20.2) mm. The tangential angles α of the cephalic trunk left common carotid artery and left subclavian artery to the aorta were (43.8°±17.1°), ß was (50.7°±14.8°), and γ was (62.4°±19.1°). Males had significantly wider D3 and D5, longer L1 and L2, and smaller gamma angles than females (P < .05). Three ECPR cases showed no recovery of the spontaneous heartbeat with femoral artery cannulation for VA-ECMO but recovered spontaneous heartbeat after axillary artery cannulation for VA-ECMO was adopted. The measurements in this study have important implications for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) procedures. They provide crucial information about arterial dimensions, including the cephalic trunk, common carotid arteries, and axillary arteries. This information guides clinicians in selecting catheters and determining the ideal depth for percutaneous axillary artery cannulation during ECMO interventions. Notable gender differences in arterial dimensions highlight the need for personalized approaches in ECMO procedures. Customizing catheter choices and cannulation depth based on individual patient characteristics, informed by these measurements, improves the safety and effectiveness of the intervention. The measured tangential angles (α, ß, and γ) offer insights into arterial alignment, crucial for optimizing cannula trajectory and ensuring proper alignment for efficient blood flow. The use of an automatic angle-forming tool enhances measurement precision, contributing to procedural accuracy and minimizing the risk of complications during ECMO procedures. In summary, these measurements directly enhance the precision and safety of VA-ECMO procedures, underscoring the importance of personalized approaches based on individual anatomical variations and improving overall intervention success and outcomes. Conclusion: Ultrasound-guided percutaneous axillary artery cannulation for VA-ECMO with a 15F cannula is clinically feasible. Axillary artery cannulation for VA-ECMO contributes to the restoration of spontaneous heartbeat in ECPR patients more than femoral artery cannulation, and the possible mechanism is a better improvement of coronary blood flow. However, the study has limitations, including a modest sample size and a single-center, retrospective design, impacting its generalizability. To validate and extend these findings, further research with larger and diverse cohorts, including prospective investigations, is necessary to ensure their applicability across various clinical settings and patient demographics in VA-ECMO.

Pseudorabies virus manipulates mitochondrial tryptophanyl-tRNA synthetase 2 for viral replication.

The pseudorabies virus (PRV) is identified as a double-helical DNA virus responsible for causing Aujeszky's disease, which results in considerable economic impacts globally. The enzyme tryptophanyl-tRNA synthetase 2 (WARS2), a mitochondrial protein involved in protein synthesis, is recognized for its broad expression and vital role in the translation process. The findings of our study showed an increase in both mRNA and protein levels of WARS2 following PRV infection in both cell cultures and animal models. Suppressing WARS2 expression via RNA interference in PK-15 cells led to a reduction in PRV infection rates, whereas enhancing WARS2 expression resulted in increased infection rates. Furthermore, the activation of WARS2 in response to PRV was found to be reliant on the cGAS/STING/TBK1/IRF3 signaling pathway and the interferon-alpha receptor-1, highlighting its regulation via the type I interferon signaling pathway. Further analysis revealed that reducing WARS2 levels hindered PRV's ability to promote protein and lipid synthesis. Our research provides novel evidence that WARS2 facilitates PRV infection through its management of protein and lipid levels, presenting new avenues for developing preventative and therapeutic measures against PRV infections.

Obesity is associated with acute kidney injury in ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention: A national representative cohort study.

BACKGROUND: Acute kidney injury (AKI) is a frequent and potentially life-threatening complication after percutaneous coronary intervention (PCI) in patients with ST-segment-elevation myocardial infarction (STEMI). However, the relationship between obesity and the risk of AKI in this specific patient population has not been previously examined. METHODS: We queried the National Inpatient Sample (2016-2019) using ICD-10 codes to obtain a sample of adults with STEMI undergoing PCI. All patients were further subcategorized into obese and nonobese cohorts. The primary outcome was the incidence of AKI. Multivariate regression analysis was performed to assess the impact of obesity on AKI. The consistency of this correlation between subgroups was investigated using subgroup analysis and interaction testing. RESULTS: A total of 62,599 (weighted national estimate of 529,016) patients were identified, of which 9.80% (n = 6137) had AKI. Obesity comprised 19.78% (n = 1214) of the AKI cohort. Obese patients were on average younger, male, white, and had more comorbidities. Additionally, there was a significant positive association between obesity and AKI incidence (adjusted odds ratio [aOR]: 1.24, 95% confidence interval [CI]: 1.15-1.34), which was more pronounced in female patients (aOR: 1.56, 95% CI: 1.33-1.82, p < 0.001, p-interaction = 0.008). The AKI incidence in these patients increased steadily during the 4-year study period, and it was consistently higher in obese patients than in nonobese patients (p-trend < 0.001 for all). CONCLUSIONS: Obesity was independently associated with a greater risk of AKI among adults with STEMI undergoing PCI, particularly in female patients.

Construction of CDKN2A-related competitive endogenous RNA network and identification of GAS5 as a prognostic indicator for hepatocellular carcinoma.

BACKGROUND: Competitive endogenous RNA (ceRNA) is an innovative way of gene expression modulation, which plays a crucial part in neoplasia. However, the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma (HCC) remain dismal. AIM: To establish a cyclin dependent kinase inhibitor 2A (CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC. METHODS: The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database. Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples. The targeted microRNAs were predicted by lncBasev3.0, and the targeted mRNAs were predicted by miRDB, and Targetscan database. The univariate and multivariate analysis were utilized to identify independent prognostic indicators. RESULTS: CDKN2A was frequently mutated and deleted in HCC. The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways. The CDKN2A-related ceRNA network-growth arrest specific 5 (GAS5)/miR-25-3p/SRY-box transcription factor 11 (SOX11) was successfully established. GAS5 was recognized as an independent prognostic biomarker, whose overexpression was correlated with a poor prognosis in HCC patients. The association between GAS5 expression and methylation, immune infiltration was explored. Besides, traditional Chinese medicine effective components targeting GAS5 were obtained. CONCLUSION: This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression. Moreover, GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.

Age-stratified analysis of HTO and UKA clinical effects in cross-indicated anterior medial osteoarthritis.

PURPOSE: To compare clinical outcomes of high tibial osteotomy (HTO) and unicompartmental knee arthroplasty (UKA) for anterior medial osteoarthritis (AMOA) as well as offer surgical recommendations through age stratification. METHODS: Between May 2019 and May 2021, 68 cross-indicated AMOA patients were analyzed. The patients were divided into HTO and UKA groups and further into two age groups of 55-60 and 60-65 years. Additionally, general data, visual analog scale (VAS) score, and Hospital for Special Surgery knee score (HSS) were analyzed. RESULTS: All the patients were followed up for 18 months. Knee joint HSS significantly improved, and VAS score decreased in both groups (P < 0.05). In the 55-60 age group, HTO showed superior knee HSS at 1 and 3 months (P < 0.05), with no significant difference at 6, 12, and 18 months. HTO had a significantly lower VAS score at one month, and the VAS scores of the two groups decreased gradually with no significant difference. In the 60-65 age group, the UKA group showed superior knee joint HSS at one month, with no significant difference at 3, 6, 12, and 18 months. The UKA group had a significantly lower VAS score at one month, and both groups' VAS scores decreased gradually with no significant difference. CONCLUSION: Both methods yield satisfactory results for AMOA cross-indications, improving knee joint function. The observed recovery trends have implications for personalized surgical recommendations, guiding interventions based on age-specific considerations for optimal outcomes in anterior medial osteoarthritis cases.

Hyperbranched Polylysine Exhibits a Collaborative Enhancement of the Antibiotic Capacity to Kill Gram-Negative Pathogens.

In recent years, traditional antibiotic efficacy outcomes have rapidly diminished due to the advent of drug resistance, and the dose limitation value has increased due to the severe side effect of globalized healthcare. Therefore, novel strategies are required to resensitize resistant pathogens to antibiotics existing in the field and prevent the emergence of drug resistance. In this study, cationic hyperbranched polylysine (HBPL-6) was synthesized using the one-pot polymerization method. HBPL-6 exhibited excellent non-cytotoxicity and bio-solubility properties. The present study also showed that HBPL-6 altered the outer membrane (OM) integrity of Escherichia coli O157:H7, Salmonella typhimurium, and Pseudomonas aeruginosa PAO1 by improving their permeability levels. When administered at a safe dosage, HBPL-6 enhanced the accumulation of rifampicin (RIF) and erythromycin (ERY) in bacteria to restore the efficacy of the antibiotics used. Moreover, the combination of HBPL-6 with colistin (COL) reduced the antibiotic dosage, which was helpful in preventing further drug-resistance outcomes. Therefore, this research provides a new strategy for reducing the dosage of drugs used to combat Gram-negative (G-) bacteria through their synergistic effects.

Distribution and analysis of subacromial spurs and the relationship with acromial classification and angle in healthy individuals.

BACKGROUND: Subacromial spurs are considered the one of the pathology underlying shoulder impingement syndrome. Furthermore, few studies have focused on the morphology of the subacromial spurs in normal Chinese people. This study aimed to study the spur distribution and to illustrate the morphology of spurs, which may help guide the extent of acromioplasty. METHODS: A total of 93 normal individuals were enrolled, and both shoulders of all enrolled individuals were analyzed. The subjects were divided and classified into three different groups by ages: group I = 18-40 years, group II = 41-60 years, and group III ≥ 61 years. The osteophyte distribution, osteophyte area, subacromial surface area and osteophyte area/subacromial surface area ratio were measured and illustrated using Mimics and 3-matic software. The shape of the acromion was classified according to the Bigliani and Morrison classification system. The acromial angle was also classified. Then, the relationship between osteophytes, acromial classification and acromial angle was analyzed. RESULTS: Type II (curved shape) was the most common type of acromion, and the hooked shape was a rare form. A significant increase in the left subacromial surface area in males was observed in group III compared with group I (P < 0.001) and group II (P = 0.004). The total spur/subacromial area ratio was significantly higher in group II than I. An obvious increase in the right subacromial area was observed in group III compared with group I (P = 0.004). Furthermore, there was a significant increase in the right spur area (P = 0.021) and total spur/subacromial area ratio (P = 0.006) in females in group II compared with group I. Fewer spurs were observed on the left than on the right side (p = 0.0482). One spur was most common among type II acromions (29/36) (80.56%) on the left side and the right side (34/52, 65.38%). CONCLUSIONS: Spurs osteophytes are mainly distributed with an irregular shape and mostly run through the medial and lateral sides of the subacromial surface in normal subjects. The characteristics of subacromial spurs are so diverse that a surgeon must conduct subacromial decompression completely based on the morphology of individual spurs.

Laser-Induced Preparation of Anderson-Type Polyoxometalate-Derived Sulfide/Oxide Electrocatalysts for Electrochemical Water Oxidation.

Developing cost-effective and high-active electrocatalysts is vital to enhance the electrocatalytic performance for oxygen evolution reaction (OER). However, traditional pyrolysis methods require complicated procedures, exact temperatures, and long reaction times, leading to high costs and low yields of electrocatalysts in potential industrial applications. Herein, a rapid and economic laser-induced preparation strategy is proposed to synthesize three bimetallic sulfide/oxide composites (MMoOS, M=Fe, Co, and Ni) on a nickel foam (NF) substrate. A focused CO2 laser with high energy is applied to decompose Anderson-type polyoxometalate (POM)-based precursors, enabling the creation of abundant heteropore and defective structures in the MMoOS composites that have multi-components of MS/Mo4O11/MoS2. Remarkably, owing to the structural interactions between the active species, FeMoOS shows superior electrocatalytic performance for OER in an alkaline medium, exhibiting a low overpotential of 240 mV at 50 mA cm-2, a small Tafel slope of 79 mV dec-1, and good durability for 80 h. Physical characterizations after OER imply that partially dissolved Mo-based species and new-formed NiO/NiOOH can effectively uncover abundant active sites, fasten charge transfer, and modify defective structures. This work provides a rapid laser-induced irradiation method for the synthesis of POM-derived nanocomposites as promoted electrocatalysts.

Feasibility and Effectiveness of Repeat Laparoscopic Pyeloplasty for Recurrent Ureteropelvic Junction Obstruction in Pediatric Patients.

Objective: To assess the outcomes of redo laparoscopic pyeloplasty (RLP) in pediatric patients with recurrent ureteropelvic junction obstruction (UPJO) in contrast to redo open pyeloplasty (ROP). In addition, evaluate the feasibility and efficacy of RLP as a treatment modality for recurrent UPJO in children. Materials and Methods: The data of 44 patients from March 2012 to March 2022, who underwent redo pyeloplasty, were retrospectively reviewed. In Group RLP, the children underwent RLP, whereas ROP was attempted in Group ROP. Demographics, clinical manifestations, surgical duration, hospitalization duration, complication rates, and treatment success were examined within the respective groups. Moreover, preoperative and postoperative measurements of anterior-posterior diameter of the renal pelvis (APD), preoperative assessment of differential renal function (DRF), and the percentage of improvement in DRF (PI-DRF) were subject to analysis. Results: The study included 28 patients who underwent RLP (Group RLP), and 16 patients who underwent ROP (Group ROP). In all cases, the Anderson-Hynes technique was employed. There was no significant difference between the two groups regarding age, body mass index, gender distribution, affected side, preoperative APD, postoperative APD, and preoperative DRF. In comparison to Group ROP, Group RLP exhibited a shorter hospitalization duration, a longer surgical procedure duration, and a higher percentage improvement in PI-DRF. The median follow-up period for Group RLP was 25 months, whereas it was 25.5 months for Group ROP. Notably, the success rates were similar between the two groups, with a success rate of 89.2% in RLP and 87.5% in ROP (p = 0.634). Conclusion: RLP has a comparable success rate to ROP and is a safe, effective, and feasible procedure for the treatment of failed pyeloplasty in children.

Receptor Tyrosine Kinase EPHA2 Drives Epidermal Differentiation through Regulation of EGFR Signaling.

Intricate signaling systems are required to maintain homeostasis and promote differentiation in the epidermis. Receptor tyrosine kinases are central in orchestrating these systems in epidermal keratinocytes. In particular, EPHA2 and EGFR transduce distinct signals to dictate keratinocyte fate, yet how these cell communication networks are integrated has not been investigated. Our work shows that loss of EPHA2 impairs keratinocyte stratification, differentiation, and barrier function. To determine the mechanism of this dysfunction, we drew from our proteomics data of potential EPHA2 interacting proteins. We identified EGFR as a high-ranking EPHA2 interactor and subsequently validated this interaction. We found that when EPHA2 is reduced, EGFR activation and downstream signaling are intensified and sustained. Evidence indicates that prolonged SRC association contributes to the increase in EGFR signaling. We show that hyperactive EGFR signaling underlies the differentiation defect caused by EPHA2 knockdown because EGFR inhibition restores differentiation in EPHA2-deficient 3-dimensional skin organoids. Our data implicate a mechanism whereby EPHA2 restrains EGFR signaling, allowing for fine tuning in the processes of terminal differentiation and barrier formation. Taken together, we purport that crosstalk between receptor tyrosine kinases EPHA2 and EGFR is critical for epidermal differentiation.

Clinical efficacy of laparoscopic Lich-Gregoir versus transvesicoscopic Cohen reimplantation for ureterobladder junction malformations in children.

OBJECTIVE: To assess the clinical efficacy of laparoscopic Lich-Gregoir (LLG) and transvesicoscopic Cohen reimplantation (TCR) in the treatment of vesicoureteral junction obstruction (VUJO) and vesicoureteral reflux (VUR). METHODS: This study retrospectively analyzed the clinical data of 66 pediatric patients with VUJO and VUR. They were classified into two groups, undergoing either the laparoscopic Lich-Gregoir operation (LLGO) (n = 35) or transvesicoscopic Cohen reimplantation operation (TCRO) (n = 31). The surgeries were performed between April 2018 and September 2022 at the First Affiliated Hospital of Guangxi Medical University, China. General characteristics, preoperative attributes, postoperative complications, renal function recovery, and improvement of hydronephrosis were compared between the two groups. RESULTS: All surgical procedures were successful with no requirement for reoperation. Both groups were comparable with respect to gender, affected side, weight, and postoperative complications. Nonetheless, the LLGO group contained a greater number of children younger than 12 months. The LLGO group demonstrated superiority over the TCRO group regarding the duration of the operation, intraoperative blood loss, and length of postoperative hospital stay. In contrast, postoperative complications, recovery of renal function, and hydronephrosis improvement did not exhibit statistically significant differences between the two groups. CONCLUSION: Both LLGO and TCRO were demonstrated to be precise, safe, and reliable surgical methods for treating pediatric VUJO and VUR. LLGO ureteral reimplantation offers particular advantages in selecting cases and appears more suitable for children younger than 12 months who have a small bladder capacity.

Measurement and Data Correction of Channel Sampling Timing Walk-Off of Photonic Analog-to-Digital Converter in Signal Recovery.

A two-channel, time-wavelength interleaved photonic analog-to-digital converter (PADC) system with a sampling rate of 10.4 GSa/s was established, and a concise method for measuring and data correcting the channel sampling timing walk-off of PADCs for signal recovery was proposed. The measurements show that for the two RF signals of f1 = 100 MHz and f2 = 200 MHz, the channel sampling timing walk-off was 12 sampling periods, which results in an ENOB = -0.1051 bits for the 100 MHz directly synthesized signal, while the ENOB improved up to 4.0136 bits using shift synthesis. In addition, the peak limit method (PLM) and normalization processing were introduced to reduce the impacts of signal peak jitter and power inconsistency between two channels, which further improve the ENOB of the 100 MHz signal up to 4.5668 bits. All signals were analyzed and discussed in both time and frequency domains. The 21.1 GHz signal was also collected and converted using the established two-channel PADC system with the data correction method, combining the PLM, normalization, and shift synthesis, showing that the ENOB increased from the initial -0.9181 to 4.1913 bits, which demonstrates that our method can be effectively used for signal recovery in channel-interleaved PADCs.

Prediction models for lymph node metastasis in cervical cancer based on preoperative heart rate variability.

Background: The occurrence of lymph node metastasis (LNM) is one of the critical factors in determining the staging, treatment and prognosis of cervical cancer (CC). Heart rate variability (HRV) is associated with LNM in patients with CC. The purpose of this study was to validate the feasibility of machine learning (ML) models constructed with preoperative HRV as a feature of CC patients in predicting CC LNM. Methods: A total of 292 patients with pathologically confirmed CC admitted to the Department of Gynecological Oncology of the First Affiliated Hospital of Bengbu Medical University from November 2020 to September 2023 were included in the study. The patient' preoperative 5-min electrocardiogram data were collected, and HRV time-domain, frequency-domain and non-linear analyses were subsequently performed, and six ML models were constructed based on 32 parameters. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Results: Among the 6 ML models, the random forest (RF) model showed the best predictive performance, as specified by the following metrics on the test set: AUC (0.852), accuracy (0.744), sensitivity (0.783), and specificity (0.785). Conclusion: The RF model built with preoperative HRV parameters showed superior performance in CC LNM prediction, but multicenter studies with larger datasets are needed to validate our findings, and the physiopathological mechanisms between HRV and CC LNM need to be further explored.

The small molecule raptinal can simultaneously induce apoptosis and inhibit PANX1 activity.

Discovery of new small molecules that can activate distinct programmed cell death pathway is of significant interest as a research tool and for the development of novel therapeutics for pathological conditions such as cancer and infectious diseases. The small molecule raptinal was discovered as a pro-apoptotic compound that can rapidly trigger apoptosis by promoting the release of cytochrome c from the mitochondria and subsequently activating the intrinsic apoptotic pathway. As raptinal is very effective at inducing apoptosis in a variety of different cell types in vitro and in vivo, it has been used in many studies investigating cell death as well as the clearance of dying cells. While examining raptinal as an apoptosis inducer, we unexpectedly identified that in addition to its pro-apoptotic activities, raptinal can also inhibit the activity of caspase-activated Pannexin 1 (PANX1), a ubiquitously expressed transmembrane channel that regulates many cell death-associated processes. By implementing numerous biochemical, cell biological and electrophysiological approaches, we discovered that raptinal can simultaneously induce apoptosis and inhibit PANX1 activity. Surprisingly, raptinal was found to inhibit cleavage-activated PANX1 via a mechanism distinct to other well-described PANX1 inhibitors such as carbenoxolone and trovafloxacin. Furthermore, raptinal also interfered with PANX1-regulated apoptotic processes including the release of the 'find-me' signal ATP, the formation of apoptotic cell-derived extracellular vesicles, as well as NLRP3 inflammasome activation. Taken together, these data identify raptinal as the first compound that can simultaneously induce apoptosis and inhibit PANX1 channels. This has broad implications for the use of raptinal in cell death studies as well as in the development new PANX1 inhibitors.

Dual-layer detector spectral CT-based machine learning models in the differential diagnosis of solitary pulmonary nodules.

The benign and malignant status of solitary pulmonary nodules (SPNs) is a key determinant of treatment decisions. The main objective of this study was to validate the efficacy of machine learning (ML) models featured with dual-layer detector spectral computed tomography (DLCT) parameters in identifying the benign and malignant status of SPNs. 250 patients with pathologically confirmed SPN were included in this study. 8 quantitative and 16 derived parameters were obtained based on the regions of interest of the lesions on the patients' DLCT chest enhancement images. 6 ML models were constructed from 10 parameters selected after combining the patients' clinical parameters, including gender, age, and smoking history. The logistic regression model showed the best diagnostic performance with an area under the receiver operating characteristic curve (AUC) of 0.812, accuracy of 0.813, sensitivity of 0.750 and specificity of 0.791 on the test set. The results suggest that the ML models based on DLCT parameters are superior to the traditional CT parameter models in identifying the benign and malignant nature of SPNs, and have greater potential for application.

Revealing the Marine Cycles of Volatile Sulfur Compounds and Their Biogeochemical Controls: A Case of the Western North Pacific.

Volatile sulfur compounds, such as dimethyl sulfide (DMS), carbonyl sulfide (OCS), and carbon disulfide (CS2), have significant implications for both atmospheric chemistry and climate change. Despite the crucial role of oceans in regulating their atmospheric budgets, our comprehension of their cycles in seawater remains insufficient. To address this gap, a field investigation was conducted in the western North Pacific to clarify the sources, sinks, and biogeochemical controls of these gases in two different marine environments, including relatively eutrophic Kuroshio-Oyashio extension (KOE) and oligotrophic North Pacific subtropical gyre. Our findings revealed higher concentrations of these gases in both seawater and the atmosphere in the KOE compared to the subtropical gyre. In the KOE, nutrient-rich upwelling stimulated rapid DMS biological production, while reduced seawater temperatures hindered the removal of OCS and CS2, leading to their accumulation. Furthermore, we have quantitatively evaluated the relative contribution of each pathway to the source and sink of DMS, OCS, and CS2 within the mixed layer and identified vertical exchange as a potential sink in most cases, transporting substantial amounts of these gases from the mixed layer to deeper waters. This research advances our understanding of sulfur gas source-sink dynamics in seawater, contributing to the assessment of their marine emissions and atmospheric budgets.

Periodic Lamellae-Based Nanofibers for Precise Immunomodulation to Treat Inflammatory Bone Loss in Periodontitis.

Periodontitis is a common oral disease accompanied by inflammatory bone loss. The pathological characteristics of periodontitis usually accompany an imbalance in the periodontal immune microenvironment, leading to difficulty in bone regeneration. Therefore, effective treatment strategies are needed to modulate the immune environment in order to treat periodontitis. Here, we developed a highly-oriented periodic lamellae poly(ε-caprolactone) electrospun nanofibers (PLN) by surface-directed epitaxial crystallization. Our in vitro results showed that the PLN could precisely modulate macrophage polarization toward the M2 phenotype. Macrophages polarized by PLN significantly enhanced the migration and osteogenic differentiation of BMSCs. Notably, results suggested that the topographical cues presented by PLN can modulate macrophage polarization by activating YAP, which reciprocally inhibits the NF-κB signaling pathway. The in vivo results indicated that PLN can inhibit inflammatory bone loss and facilitate bone regeneration in periodontitis. Our findings suggest that topographical nanofibers with periodic lamellae is a promising strategy for modulating immune environment to treat inflammatory bone loss in periodontitis. This article is protected by copyright. All rights reserved.