"No-Touch" Left Approach for Recipient Hepatectomy: A Promising Strategy to Minimize Hepatocellular Carcinoma Recurrence in Liver Transplantation.

Background: Managing hepatocellular carcinoma (HCC) presents significant clinical challenges, often necessitating orthotopic liver transplantation (OLT). To mitigate the risk of iatrogenic metastasis during OLT and reduce posttransplantation recurrence (PTR), we introduced the "no-touch" left (NTL) approach for recipient hepatectomy in OLT. Methods: In this retrospective cohort study, our aim was to compare the safety and PTR rates in patients undergoing OLT via either the NTL technique or the conventional approach for recipient hepatectomy. We included 106 patients who met the Hangzhou criteria and exhibited a high tumor burden in the right lobe, with 50 patients assigned to the NTL group and 56 to the conventional group. The primary endpoint was the 1-y PTR rate, whereas secondary endpoints encompassed the safety of the NTL approach, PTR rates at 2 and 5 y, and overall survival. Results: Baseline demographics and clinical characteristics showed no significant differences between the groups. The NTL approach exhibited major surgical outcomes similar to those of the conventional approach. The cumulative PTR rates at 1, 2, and 5 y were 14.0% in the NTL group, compared with 24.5%, 35.8%, and 35.8% in the conventional group (P = 0.013). Cumulative overall survival rates at 1, 2, and 5 y were 94.0%, 91.9%, and 89.7% in the NTL group and 88.7%, 75.5%, and 72.5% in the conventional group (P = 0.03). Conclusions: This innovative surgical technique enhances safety and significantly reduces the risk of PTR, leading to improved long-term survival. Further prospective studies with larger cohorts and longer follow-up periods are needed to validate our findings and establish the NTL approach as a standard practice in OLT.

Individualized management of immunosuppressants in liver transplant recipients by using a novel immune score system.

BACKGROUND: There is no reliable means to evaluate the immune status of liver transplant recipients. We proposed a novel score model, namely Mingdao immune cell analysis and Mingdao immune score system, to quantify the immunity. METHODS: Data from those who underwent a single liver transplant between January 2017 and June 2020 at Beijing Chaoyang Hospital, were collected. In addition, healthy volunteers were also enrolled. The score model was based on the immune cell populations determined by flow cytometry. RESULTS: There were a total of 376 healthy controls with 376 tests and 148 liver transplant recipients with 284 tests in this study. Evaluated by Mingdao immune cell analysis and Mingdao immune score system, the mean scores of healthy controls were near zero suggesting a balanced immune system. In contrast, the mean scores of liver transplant recipients were negative both before and after surgery indicating a compromised immune system. When liver transplant recipients were given a reduced or routine first dose according to their preoperative score, they had similar recovery of liver function. Moreover, liver transplant recipients with increased scores ≥ 5 were associated with elevated aspartate transaminase and alanine amiotransferase. Finally, on multivariate analysis the score model was the only significant independent risk factor for clinical acute rejection (P = 0.021; Odds ratio, 0.913; 95% confidence interval, 0.845-0.987). CONCLUSION: The novel score model could be used as an indicator to reflect immunity and to regulate immunosuppressants in liver transplant recipients after surgery.

A Pump-Free Strategy for the Controllable Generation of Alginate Microgels as Cellular Microcarriers.

Microgels are advanced scaffolds for tissue engineering due to their proper biodegradability, good biocompatibility, and high specific surface area for effective oxygen and nutrient transfer. However, most of the current monodispersed microgel fabrication systems rely heavily on various precision pumps, which highly increase the cost and complexity of their downstream application. In this work, we developed a simple and facile system for the controllable generation of uniform alginate microgels by integrating a gas-shearing strategy into a glass microfluidic device. Importantly, the cell-laden microgels can be rapidly prepared in a pump-free manner under an all-aqueous environment. The three-dimensional cultured green fluorescent protein-human A549 cells in alginate microgels exhibited enhanced stemness and drug resistance compared to those under two-dimensional conditions. The pancreatic cancer organoids in alginate microgels exhibited some of the key features of pancreatic cancer. The proposed microgels showed decent monodispersity, biocompatibility, and versatility, providing great opportunities in various biomedical applications such as microcarrier fabricating, organoid engineering, and high-throughput drug screening.

Serum phosphorus concentration and its association with the degree and pattern of intracranial arterial calcification.

BACKGROUND AND AIM: The aim of this study was to determine whether the serum phosphorus concentrations (SPC) are associated with the degree and pattern of intracranial arterial calcification (IAC) in patients with normal renal function or mild-moderate renal impairment. METHODS AND RESULTS: A total of 513 patients were enrolled in this study. The degree of IAC measured by IAC scores was evaluated on non-contrast head computed tomography (CT) images and IAC was classified as intimal or medial calcification. Study participants were classified according to IAC degrees (mild, moderate and severe) and patterns (intimal and medial calcification). A multivariate regression model was used to assess the independent relationship of SPC with IAC scores and patterns. Of 513 study participants (mean [SD] age, 68.3 [10.3] years; 246 females [48%]), the mean SPC was 1.07 ± 0.17 mmol/L and IAC scores was 4.0 (3.0-5.0). Multivariate analysis showed that higher serum phosphorus was a significant risk factor for moderate/severe IAC in both patients with eGFR ≥60 ml/min/1.73 m2 (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.01-1.59; P < 0.05) and eGFR <60 ml/min/1.73 m2 (OR, 1.92; 95% CI, 1.04-3.57; P < 0.05), when those with mild IAC were considered as the reference group. However, higher SPC was associated with an increased odds of medial calcification only in patients with eGFR <60 ml/min/1.73 m2 (OR, 1.67; 95% CI, 1.08 to 2.61). CONCLUSIONS: High levels of serum phosphorus were positively correlated with the degree of IAC, and this significant effect on medial IAC was only present in patients with impaired renal function (eGFR <60 ml/min/1.73 m2).

Impact of the diagnosis of metabolic dysfunction-associated fatty liver disease and non-alcoholic fatty liver disease in patients undergoing liver transplantation for hepatocellular carcinoma.

Purpose: Whether the diagnosis of non-alcoholic fatty liver disease or metabolic dysfunction-associated fatty disease has a different impact on liver transplant recipients with hepatocellular carcinoma is not yet clear. Methods: Data from a two-center retrospective cohort study were collected to compare and investigate the differences between non-alcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease in clinicopathologic parameters and prognosis among liver transplant recipients with hepatocellular carcinoma. Results: A total of 268 liver transplant recipients with hepatocellular carcinoma were included. The prevalence among pre- and post-transplant metabolic dysfunction-associated fatty liver disease was 10.82% and 30.22%, while for non-alcoholic fatty liver disease, it was 7.09% and 26.87%, respectively. The clinicopathological parameters were similar between the two pre-transplant groups. In contrast, the post-transplant group with metabolic dysfunction-associated fatty liver disease exhibited a higher prevalence of diabetes mellitus and a greater body mass index. However, the other parameters were similar between the two post-transplant groups (p > 0.05). Factors such as the largest tumor size > 4 cm, microvascular invasion, lack of tumor capsule, post-transplant metabolic dysfunction-associated fatty liver disease, and decreased post-transplant lymphocyte percentage were related to an increased risk of recurrence. Conclusion: In patients undergone liver transplantation for hepatocellular carcinoma, the diagnosis of metabolic dysfunction-associated fatty disease is more strongly associated with metabolic abnormalities than the diagnosis of non-alcoholic fatty liver disease and is an independent predictor of hepatocellular carcinoma recurrence.

Granzyme B+ B cells detected by single-cell sequencing are associated with prognosis in patients with intrahepatic cholangiocarcinoma following liver transplantation.

B cells possess anti-tumor functions mediated by granzyme B, in addition to their role in antigen presentation and antibody production. However, the variations in granzyme B+ B cells between tumor and non-tumor tissues have been largely unexplored. Therefore, we integrated 25 samples from the Gene Expression Omnibus database and analyzed the tumor immune microenvironment. The findings uncovered significant inter- and intra-tumoral heterogeneity. Notably, single-cell data showed higher proportions of granzyme B+ B cells in tumor samples compared to control samples, and these levels were positively associated with disease-free survival. The elevated levels of granzyme B+ B cells in tumor samples resulted from tumor cell chemotaxis through the MIF- (CD74 + CXCR4) signaling pathway. Furthermore, the anti-tumor function of granzyme B+ B cells in tumor samples was adversely affected, potentially providing an explanation for tumor progression. These findings regarding granzyme B+ B cells were further validated in an independent clinic cohort of 40 liver transplant recipients with intrahepatic cholangiocarcinoma. Our study unveils an interaction between granzyme B+ B cells and intrahepatic cholangiocarcinoma, opening up potential avenues for the development of novel therapeutic strategies against this disease.

Impact of metabolic dysfunction-associated fatty liver disease on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease was proposed by international consensus to redefine the metabolic abnormal condition. However, its impact on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma has not been explored. METHODS: A two-center retrospective cohort study on liver transplant recipients with hepatitis B virus-related hepatocellular carcinoma was performed to analyze the impact of metabolic dysfunction-associated fatty liver disease on the clinicopathologic parameters and prognosis. RESULTS: There were 201 liver transplant recipients enrolled from two hospitals in our study. The pre- and post-transplant prevalences of metabolic dysfunction-associated fatty liver disease were 9.95% and 28.86%, respectively. The clinicopathological parameters revealed a similarity between patients with and without pre-transplant metabolic dysfunction-associated fatty liver disease. In contrast, the group with post-transplant metabolic dysfunction-associated fatty liver disease was linked with older age, a higher hepatitis recurrence rate and incidence of cardiovascular disease, usage of calcineurin inhibitors, a greater body mass index and waist circumference, lower albumin and high-density lipoprotein cholesterol levels, and poorer tumor-free survival and overall survival. The multivariate analysis showed the largest tumor size >4 cm (95% confidence intervals: 0.06~0.63, p = 0.006), microvascular invasion (95% confidence intervals: 1.61~14.92, p = 0.005), post-transplant metabolic dysfunction-associated fatty liver disease (95% confidence intervals: 1.40~10.60, p = 0.009), and calcineurin inhibitors-based regimen (95% confidence intervals: 0.33~0.96, p = 0.036) were the independent risk factors for recurrent hepatocellular carcinoma. CONCLUSIONS: Our study suggests that post-transplant metabolic dysfunction-associated fatty liver disease is more closely to metabolic abnormalities and that it can help identify liver transplant recipients at high risk of recurrent hepatocellular carcinoma.

High-performance and functional fully bio-based polylactic acid/polypropylene carbonate blends by in situ multistep reaction-induced interfacial control.

Using a solvent-free radical grafting technique, glycidyl methacrylate (GMA) and maleic anhydride (MAH) were used as functionalized graft monomers, styrene (St) as a copolymer monomer, and grafted onto polylactic acid (PLA). A series of PLA-g-(GMA/MAH-co-St) graft copolymers were prepared by adjusting the GMA/MAH ratio. Subsequently, the prepared graft copolymers were used as a compatibilizer with PLA and polypropylene carbonate (PPC) for melt blending to prepare PLA/PPC/PLA-g-(GMA/MAH-co-St) blends. The effects of changes in the GMA/MAH ratio in the graft copolymer on the thermodynamics, rheology, optics, degradation performance, mechanical properties, and microstructure of the blend were studied. The results found that GMA, MAH, and St were successfully grafted onto PLA, and the PLA-g-(GMA/MAH-co-St) graft copolymer obtained from the reaction had a good toughening effect on the PLA/PPC blend system, which significantly improved the mechanical properties of the PLA/PPC/PLA-g-(GMA/MAH-co-St) blend without reducing its degradation performance, resulting in a biodegradable blend material with excellent comprehensive performance. In the PLA-g-(GMA/MAH-co-St) grafting reaction system, when GMA/MAH = 1.5/1.5 (w/w), the grafting degree of the graft copolymer increased most significantly, from 0.83 phr to 1.51 phr. This composition of graft copolymer can effectively improve the compatibility between PLA and PPC. The resulting PLA/PPC blend can maintain good melt flow properties (MFR of 14.51 g/10 min), high transparency, and low haze (light transmittance of 91.56 %, haze of 20.5 %), while significantly improving its thermal stability (T95%, Tmax, and Et increased by 12.87 °C, 20.33 °C, and 32.00 kJ/mol, respectively). Moreover, when introducing PLA-g-(GMA/MAH-co-St) (GMA/MAH = 1.5/1.5 (wt/wt)) graft copolymer into the system, the toughness of the PLA/PPC/PLA-g-(GMA/MAH-co-St) blend system is optimal, with the notch impact strength and fracture elongation increasing to 184.6 % and 535.4 % of the PLA/PPC blend, respectively, at which point the fracture surface of the impact sample shows a wrinkled fracture feature indicative of toughness.

Improving the properties of polylactic acid/polypropylene carbonate blends through cardanol-induced compatibility enhancement.

Cardanol (CD) is used as a reactive compatibilizer, and blended with polylactic acid (PLA) and polypropylene carbonate (PPC) resin (70/30(w/w)) to obtain a series of PLA/PPC/CD blends. The systematic study was conducted on the thermal properties, optical properties, rheological properties, mechanical properties, and microscopic morphology of the blend, by varying amounts of CD added to the blends. A detailed explanation and comprehensive analysis of the reaction mechanism between CD and PLA/PPC have been made. The study found that CD acts as a "bridge" between the PLA and PPC, forming the structure of a block copolymer (PLA-b-CD-b-PPC), and the copolymer can greatly improve the compatibility of PLA and PPC. When the amount of CD reaches 8 wt%, only one Tg is observed in the blend, simultaneously, PLA/PPC has already transitioned from a partially compatible system to a completely compatible system. At the same time, the addition of CD does not have any negative impact on the thermal stability of the PLA/PPC blend under processing temperature conditions, and the thermal stability of the PLA/PPC/CD blends can even be improved under extreme conditions. In addition, the addition of CD allows the PLA/PPC/CD blends to maintain a high light transmittance while reducing the opacity of the blend (the light transmittance remains above 92 %, and the opacity is reduced from 37 % to about 24 %), demonstrating excellent optical properties. Moreover, the elongation at break and impact strength of the PLA/PPC/CD blend both show a trend of first increasing and then decreasing with the increase of CD amount. When the CD amount varies within the range of 6- 8 wt%, the blends undergoes a brittle-ductile transition, and its toughness is greatly improved while the rigidity can also meet practical needs. When the amount of CD in the system increases to 12 wt%, the toughness of the blend reaches its peak, and its elongation at break and impact strength reach 513.24 % and 9211.5 J/m2 respectively (increased to 2442.84 % and 270.73 % of the PLA/PPC blend). Concurrently, the fracture surface of the blend exhibits large-scale plastic flow in the direction of the applied force, with marked shear yield phenomena, showing obvious characteristics of tough fracture.

Improvement of properties of polylactic acid/polypropylene carbonate blends using epoxy soybean oil as an efficient compatibilizer.

Epoxidized soybean oil (ESO) was used as a compatibilizer and blended with polylactic acid (PLA) and polypropylene carbonate (PPC) resin to prepare a series of PLA/PPC/ESO blends with varying compositions. The influence of the variation in the amount of ESO added to the blend system on the thermal properties, optical properties, rheological properties, mechanical properties, and microscopic morphology of the blends was studied. The research indicates that ESO can react with PLA and PPC to form a chemical bond interface, which improves the compatibility of PLA and PPC to a certain extent. With the increase in the amount of ESO added to the blend (1- 5 phr), the complete decomposition temperature, storage modulus, loss modulus, complex viscosity, notched impact strength, and elongation at break of the blend all show a trend of continuous increase. At the same time, the melt flow rate, light transmittance, and tensile strength of the blend do not show significant fluctuations. When the amount of ESO in the system is 5 phr, compared with the PLA/PPC blend, the notched impact strength and elongation at break of the PLA/PPC/ESO blend increase from 4270.3 J/m2, 43.89 % to 8560.4 J/m2, 211.28 %, respectively, and its tensile strength and transmittance still remain around 63 MPa, 92 %. This improves the toughness of the blend while maintaining its rigidity, demonstrating excellent mechanical and optical properties. At this time, the microscopic morphology of the fracture surface of the impact sample also shows obvious characteristics of tough fracture. However, when the amount of ESO added to the blend is excessive (6 phr), the compatibility of the blending system decreases, which will degrade the performance of the blending material and ultimately destroy the phase morphology of the blend and reduce its mechanical properties.

Effect of Octene Block Copolymer (OBC) and High-Density Polyethylene (HDPE) on Crystalline Morphology, Structure and Mechanical Properties of Octene Random Copolymer.

Blending octene random copolymer (ORC) with other polymers is a promising approach to improving ORC mechanical properties, such as tensile strength and elongation. In this study, octene block copolymer (OBC) with lower density than ORC and high-density polyethylene (HDPE) were used to blend with ORC. The effect of both OBC and HDPE on ORC was analyzed using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA) and small-angle X-ray scattering (SAXS). For ORC/OBC blends, a small amount of OBC can improve the crystallization ability of ORC. Meanwhile, for ORC/HDPE blends, the crystallization ability of ORC was significantly suppressed, attributed to good compatibility between ORC and HDPE as indicated by the homogeneous morphology and the disappearance of the α transition peak of ORC in ORC/HDPE blends. Therefore, the tensile strength and elongation of ORC/HDPE blends are significantly higher than those of ORC/OBC blends. For ORC/OBC/HDPE ternary blends, we found that when ORC:OBC:HDPE are at a ratio of 70:15:15, cocrystallization is achieved. Although HDPE improves the compatibility of ORC and OBC, the three-phase structure of the ternary blends can be observed through SAXS when HDPE and OBC exceed 30 wt%. Blending HDPE and OBC (≤30 wt%) could improve the mechanical property of ORC.

The Effect of Functionalized SEBS on the Properties of PP/SEBS Blends.

Styrene (St) was used as comonomer and glycidyl methacrylate (GMA) as grafting monomer to prepare SEBS-g-(GMA-co-St) graft copolymers via melt grafting. Then, the graft copolymers were employed as a compatibilizer for melt blending polypropylene (PP) and hydrogenated styrene-butadiene-styrene (SEBS) triblock copolymers. The effects of the amount of GMA in the graft copolymers on thermal properties, rheology, crystallization, optical and mechanical properties, and microstructure of the blends were investigated. The results show that GMA and St were successfully grafted onto SEBS. The GMA amount in the graft copolymer significantly influenced the comprehensive properties of PP/SEBS/SEBS-g-(GMA-co-St) blends. The epoxy groups of GMA reacted with PP and SEBS, forming interfacial chemical bonds, thereby enhancing the compatibility between PP and SEBS to varying extents. After introducing SEBS-g-(GMA-co-St) into PP/SEBS blends, crystallinity decreased, crystal size increased while transmittance remained above 91% with rising GMA amount in the graft copolymers, indicating excellent optical properties. Notched impact strength and elongation at break of the blends showed a trend of first increasing and then decreasing with increased amounts of GMA in the graft copolymers. When the amount of GMA in the graft copolymers was 3 wt%, the blends exhibited optimal toughness with notched impact strength and elongation at break of 30,165.82 J/m2 and 1445.40%, respectively. This was attributed to the tightest dispersion interface adhesion and maximum matrix plastic deformation, consistent with the mechanical performance results.

Novel mesothelin-targeted chimeric antigen receptor-modified UNKT cells are highly effective in inhibiting tumor progression.

The design of chimeric antigen receptors (CAR) significantly enhances the antitumor efficacy of T cells. Although some CAR-T products have been approved by FDA in treating hematological tumors, adoptive immune therapy still faces many difficulties and challenges in the treatment of solid tumors. In this study, we reported a new strategy to treat solid tumors using a natural killer-like T (NKT) cell line which showed strong cytotoxicity to lyse 15 cancer cell lines, safe to normal cells and had low or no Graft-versus-host activity. We thus named it as universal NKT (UNKT). In both direct and indirect 3D tumor-like organ model, UNKT showed efficient tumor-killing properties, indicating that it could penetrate the microenvironment of solid tumors. In mesothelin (MSLN)-positive tumor cells (SKOV-3 and MCF-7), MSLN targeting CAR modified-UNKT cells had enhanced killing potential against MSLN positive ovarian cancer compared with the wild type UNKT, as well as MSLN-CAR-T cells. Compared with CAR-T, Single-cell microarray 32-plex proteomics revealed CAR-UNKT cells express more effector cytokines, such as perforin and granzyme B, and less interleukin-6 after activation. Moreover, our CAR-UNKT cells featured in more multifunctionality than CAR-T cells. CAR-UNKT cells also demonstrated strong antitumor activity in mouse models of ovarian cancer, with the ability to migrate and infiltrate the tumor without inducing immune memory. The fast-in and -out, enhanced and prolonged tumor killing properties of CAR-UNKT suggested a novel cure option of cellular immunotherapy in the treatment of MSLN-positive solid tumors.

Association between Obstructive Sleep Apnea and Intracranial Artery Calcification Stratified by Gender and Body Mass Index: A Hospital-Based Observational Study.

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea (OSA) is an independent risk factor for stroke. Furthermore, intracranial arterial calcification (IAC) has been validated as a marker for subclinical cerebrovascular disease. However, the relationship between OSA with IAC was less studied compared with its established association with coronary artery calcification. In this study, we aimed to investigate the association between the severity of OSA and the degree of IAC in hospitalized patients without preexisting cardiovascular disease. METHODS: This hospital-based observational study was conducted from June 1, 2017, to May 1, 2019. In total, 901 consecutive patients who underwent head computed tomography scans and portable sleep monitoring were included. On the basis of the apnea-hypopnea index (AHI), patients were divided into four OSA severity groups (normal: AHI <5/h; mild: 5≤ AHI <15/h; moderate: 15≤ AHI <30/h; severe: AHI ≥30/h). Associations of OSA with IAC scores were assessed by using multivariate logistic regression analysis. RESULTS: Of the 901 patients, 484 (53.7%) were men; the mean (SD) age was 66.1 (10.0) years. The non-OSA group included 207 (23.0%) patients; mild OSA, 209 (23.2%); moderate OSA, 235 (26.1%); and severe OSA, 169 (18.8%). Mean IAC scores were higher in the severe OSA group compared with non-, mild, and moderate OSA groups (4.79 vs. 2.58; 4.79 vs. 2.94; 4.79 vs. 3.39; p < 0.001). Multivariate analysis adjusted for confounding factors revealed that only severe OSA was associated with a higher IAC score (odds ratio [OR]: 1.65; 95% confidence interval [CI]: 1.43-1.91; p < 0.001). In stratified analyses by BMI, among participants with a BMI <25 kg/m2, the positive association between AHI values and IAC scores was found in the moderate OSA group (OR: 1.23; 95% CI: 1.05, 1.43; p = 0.01) and the severe OSA group (OR: 1.96; 95% CI: 1.55, 2.48; p < 0.001). When stratified by gender, in women, the positive association was found in the moderate OSA group (adjusted OR: 1.21; 95% CI: 1.02-1.51; p = 0.016) and the severe OSA group (adjusted OR: 1.76; 95% CI: 1.36-2.25; p < 0.001). For the men group, a positive association between IAC scores and AHI was only observed in the severe OSA group. DISCUSSION: These findings suggest that OSA, in particular severe OSA (AHI ≥30), is independently associated with higher IAC scores. Women and no-obesity individuals appeared more susceptible to adverse OSA-related subclinical cerebrovascular disease as measured by IAC scores.

Brachial-ankle pulse wave velocity is associated with intracranial artery calcification in acute stroke patients.

BACKGROUND: Intracranial artery calcification (IAC) is closely associated with cerebrovascular disease. Brachial-ankle pulse wave velocity (baPWV) is a noninvasive method for estimating arterial stiffness, which reflects the stiffness of peripheral arteries. This study aimed to examine the association of baPWV with the presence and degree of IAC in patients with acute ischemic stroke. METHODS: A total of 143 ischemic stroke subjects were recruited. A head computed tomography (CT) scan was used to assess the presence and severity of IAC. The oscillometric method was used to simultaneously measure bilateral brachial and posterior tibial arterial pulse waveforms and arterial BP. Multiple logistic regression analysis was used to identify the independent relationship between baPWV and IAC. RESULTS: 143 subjects were included in this study. The demographic and clinical characteristics of the study population were classified according to the baPWV quartile. A higher prevalence of IAC was noted across increasing baPWV quartiles (Q1: 53 %, Q2: 69 %, Q3: 86 %, Q4: 94 %, P < 0.001). IAC scores were also increased with elevated ccPWV values (1.60 ± 1.71; 2.56 ± 1.99; 3.44 ± 1.91; 4.64 ± 1.58. P < 0.001). After an additional adjustment for age and hypertension, the odds ratio (95 % confidence interval) for the IAC scores was 1.61 (1.06-2.45; P = 0.025) in the top quartile of baPWV compared with those in the lowest quartile. CONCLUSIONS: Arterial stiffness as defined by baPWV was positively associated with the degree of IAC in patients with acute ischemic stroke, suggesting the severity of IAC may also be a marker of peripheral or systemic arterial stiffness.

A non-enzymatic glucose sensor based on a mesoporous carbon sphere immobilized Co-MOF-74 nanocomposite.

Exploration of credible non-enzymatic glucose sensors with high selectivity and sensitivity is of great significance for early clinical monitoring of glucose concentration and preventing the threat of diabetes to human health. Here, mesoporous carbon (MC) sphere immobilized Co-MOF-74 nanorods (NRs), denoted as Co-MOF-74 NRs/MC, were successfully prepared, in which the nanostructural porous carbon sphere was obtained using cobalt glycolate as the built-in template followed by a subsequent carbonization and acid treatment, and the MC spheres were then in situ deposited on the surface of Co-MOF-74 NRs via a solvothermal method. Benefiting from the good conductivity of the grafted porous carbon spheres and the abundant active sites, as well as the permeability of microporous MOF-74 nanocrystals, the Co-MOF-74 NRs/MC modified glassy carbon electrode (GCE) exhibited effective non-enzymatic glucose sensing performance with a fast response time (less than 3 s) and a glucose sensitivity of 98.0 µA cm-2 mM-1. Furthermore, the Co-MOF-74 NRs/MC/GCE showed a favourable anti-interference capability in the presence of various interferents and good long-term reusability. The applicability of Co-MOF-74 NRs/MC/GCE for glucose sensing in real serum samples was also investigated, verifying the applicability of the electrode for targeted glucose monitoring in practical applications.

Critical closing pressure as a new hemodynamic marker of cerebral small vessel diseases burden.

Purpose: To investigate cerebrovascular hemodynamics, including critical closing pressure (CrCP) and pulsatility index (PI), and their independent relationship with cerebral small vessel disease (CSVD) burden in patients with small-vessel occlusion (SVO). Methods: We recruited consecutive patients with SVO of acute cerebral infarction who underwent brain magnetic resonance imaging (MRI), transcranial Doppler (TCD) and CrCP during admission. Cerebrovascular hemodynamics were assessed using TCD. We used the CSVD score to rate the total MRI burden of CSVD. Multiple regression analysis was used to determine parameters related to CSVD burden or CrCP. Results: Ninety-seven of 120 patients (mean age, 64.51 ± 9.99 years; 76% male) completed the full evaluations in this study. We observed that CrCP was an independent determinant of CSVD burden in four models [odds ratio, 1.41; 95% confidence interval (CI), 1.17-1.71; P < 0.001] and correlated with CSVD burden [ß (95% CI): 0.05 (0.04-0.06); P < 0.001]. In ROC analysis, CrCP was considered as a predictor of CSVD burden, and AUC was 86.2% (95% CI, 78.6-93.9%; P < 0.001). Multiple linear regression analysis showed that CrCP was significantly correlated with age [ß (95% CI): 0.27 (0.06 to 0.47); P = 0.012], BMI [ß (95% CI): 0.61 (0.00-1.22)] and systolic BP [ß (95% CI): 0.16 (0.09-0.23); P < 0.001]. Conclusions: CrCP representing cerebrovascular tension is an independent determinant and predictor of CSVD burden. It was significantly correlated with age, BMI and systolic blood pressure. These results provide new insights in the mechanism of CSVD development.

Cerebral Arterial Stiffness as Measured Based on the Pulse Wave Velocity is Associated With Intracranial Artery Calcification in Patients With Acute Stroke.

BACKGROUND AND PURPOSE: By measuring a newly defined parameter, the carotid-cerebral pulse wave velocity (ccPWV), this study aimed to determine the association of intracranial artery calcification (IAC) with arterial stiffness as reflected by the pulse wave velocity between the carotid and middle cerebral arteries using transcranial Doppler sonography in patients with acute stroke. METHODS: We recruited 146 patients with ischemic stroke from our stroke center. Computed tomography of the head was used to assess the presence and severity of IAC. Arterial stiffness was evaluated using ccPWV. Data are presented as quartiles of ccPWV. A multivariable logistic regression model was used to assess the independent relationship between ccPWV and IAC. RESULTS: The IAC prevalence increased with the ccPWV quartile, being 54%, 76%, 83%, and 89% for quartiles 1, 2, 3, and 4, respectively (p<0.001) as did IAC scores, with median [interquartile range] values of 0 [0-2], 3 [2-4], 4 [2-5], and 5 [4-6], respectively (p<0.001). After additionally adjusting for age and hypertension, a significant correlation was only found between quartiles 3 and 4 of ccPWV and IAC scores. The odds ratio (95% confidence interval) for the IAC scores was 1.78 (1.28-2.50) (p=0.001) in quartile 4 of ccPWV and 1.45 (1.07-1.95) (p=0.015) in quartile 3 compared with quartile 1. CONCLUSIONS: We found that in patients with acute ischemic stroke, ccPWV was positively related to the degree of IAC. Future longitudinal cohort studies may help to identify the potential role of IAC in the progression of cerebral arterial stiffness.

Collagen type VII α1 chain: A promising prognostic and immune infiltration biomarker of pancreatic cancer.

Pancreatic cancer (PC) is a stubborn malignancy with high lethality and a low 5-year overall survival (OS) rate. Collagen type VII α1 chain (COL7A1), a major component of the extracellular matrix, serves important roles in numerous physiological processes and various illnesses. COL7A1 protein acts as an anchoring fibril between the external epithelial cells and the underlying stroma, and mutation of COL7A1 could cause recessive dystrophic epidermolysis bullosa. Raw data for PC were acquired from The Cancer Genome Atlas and the Gene Expression Omnibus database, and raw data for the normal pancreas were obtained from the Genotype-Tissue Expression database. COL7A1 mRNA expression in PC tissues was compared with that in either paired (GSE15471 dataset) or unpaired (all other data) normal pancreas tissues. The association between COL7A1 mRNA expression and clinicopathological factors was assessed using logistic regression analysis. Cox analysis and Kaplan-Meier analysis were used to evaluate the role of COL7A1 mRNA expression in prognosis and nomograms were constructed. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, Gene Set Enrichment Analysis (GSEA) and single-sample GSEA (ssGSEA) were performed to evaluate the relevant functions of COL7A1 and correlation with immune cell infiltration. Furthermore, reverse transcription-quantitative PCR was used to assess the mRNA expression levels of COL7A1 in PC. The present study demonstrated that COL7A1 mRNA expression was higher in PC tissues compared with in normal pancreas tissues. The Kaplan-Meier survival analysis indicated that patients with PC with high COL7A1 mRNA expression had shorter overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) times compared with patients with PC with low COL7A1 mRNA expression. Multivariate analysis demonstrated that COL7A1 mRNA expression was an independent risk factor for OS, DSS and PFI. Nomogram and calibration plots were constructed to predict the prognosis of patients with PC. GSEA demonstrated that high mRNA expression levels of COL7A1 were associated with multiple cancer-related pathways. ssGSEA analysis indicated that COL7A1 expression was positively associated with natural killer CD56bright cells and T helper (Th)2 cells, and negatively associated with Th17 cells and eosinophils. The results of the present study suggested that COL7A1 could be an independent biomarker and an influential moderator of immune infiltration in PC.

Double Stimuli-Responsive Conducting Polypyrrole Nanocapsules for Corrosion-Resistant Epoxy Coatings.

Stimuli-responsive nanocapsules, which can respond to various environmental stimuli and release their encapsulated payload on demand, have attracted wide interest in different fields in recent years. In this work, a novel kind of polypyrrole (PPy) nanocapsules is fabricated and loaded with zinc salt corrosion inhibitors. The synthesized PPy nanocapsules respond to two different external stimuli (pH- and redox-responsive) and can control the release of their encapsulated corrosion inhibitors. The nanocapsules can detect the micro-environmental pH or surface-potential changes associated with the corrosion initiation of the metal substrate. When introduced into a protective epoxy coating, the fabricated PPy nanocapsules inhibit the anodic and cathodic corrosion reactions. The superior corrosion resistance and active corrosion protection effects of the epoxy-PPy-Zn coatings are further demonstrated via electrochemical and long-term immersion tests. The low-frequency impedance, coating resistance, and oxide film resistance increase after about 400 h of exposure in a 3.5 wt % NaCl solution, reflecting the enhanced corrosion protection properties and excellent repairing performance of the coating. Furthermore, the epoxy-PPy-Zn coating can avoid the pitting corrosion of 304 stainless steel. Overall, we have fabricated double stimuli-responsive PPy nanocapsules via a simple and effective strategy and incorporated them into a corrosion-resistant epoxy coating for protecting Fe-based metal substrates.