Nanolignin-Facilitated Robust Hydrogels.

Recently, certain challenges and accompanying drawbacks have emerged in the preparation of high-strength and tough polymer hydrogels. Insights from wood science highlight the role of the intertwined molecular structure of lignin and crystalline cellulose in contributing to wood's strength. Herein, we immersed prestretched poly(vinyl alcohol) (PVA) polymer hydrogels into a solution of nanosized lignosulfonate sodium (LS), a water-soluble anionic polyelectrolyte, to creatively reconstruct this similar structure at the molecular scale in hydrogels. The nanosized LS effectively fixed and bundled the prestretched PVA polymers while inducing the formation of dense crystalline domains within the polymer matrix. Consequently, the interwoven structure of crystalline PVA and LS conferred good strength to the composite hydrogels, exhibiting a tensile strength of up to ∼23 MPa, a fracture strain of ∼350%, Young's modulus of ∼17 MPa, toughness of ∼47 MJ/m3, and fracture energy of ∼42 kJ/m2. This hydrogel far outperformed previous hydrogels composed directly of lignin and PVA (tensile strength <1.5 MPa). Additionally, the composite hydrogels demonstrated excellent antifreezing properties (<-80 °C). Notably, the LS-assisted reconstruction technology offers opportunities for the secondary fixation of PVA hydrogel shapes and high-strength welding of hydrogel components. This work introduces an approach for the high-value utilization of LS, a green byproduct of pulp production. LS's profound biomimetic strategy will be applied in multifunctional hydrogel fields.

Tough Supramolecular Hydrogels Crafted via Lignin-Induced Self-Assembly.

Supramolecular hydrogels are typically assembled through weak non-covalent interactions, posing a significant challenge in achieving ultra strength. Developing a higher strength based on molecular/nanoscale engineering concepts is a potential improvement strategy. Herein, a super-tough supramolecular hydrogel is assembled by gradually diffusing lignosulfonate sodium (LS) into a polyvinyl alcohol (PVA) solution. Both simulations and analytical results indicate that the assembly and subsequent enhancement of the crosslinked network are primarily attributed to LS-induced formation and gradual densification of strong crystalline domains within the hydrogel. The optimized hydrogel exhibits impressive mechanical properties with tensile strength of ≈20 MPa, Young's modulus of ≈14 MPa, and toughness of ≈50 MJ m⁻3, making it the strongest lignin-PVA/polymer hydrogel known so far. Moreover, LS provides the supramolecular hydrogel with excellent low-temperature stability (<-60 °C), antibacterial, and UV-blocking capability (≈100%). Interestingly, the diffusion ability of LS is demonstrated for self-restructuring damaged supramolecular hydrogel, achieving 3D patterning on hydrogel surfaces, and enhancing the local strength of the freeze-thaw PVA hydrogel. The goal is to foster a versatile hydrogel platform by combining eco-friendly LS with biocompatible PVA, paving the way for innovation and interdisciplinarity in biomedicine, engineering materials, and forestry science.

Effects of Misalignment of c-axis on the Properties of Hydrogenation-Disproportionation-Desorption-Recombination Particles.

Hydrogenation-Disproportionation-Desorption-Recombination (HDDR) Nd2Fe14B particles have excellent magnetic properties, but the magnetic properties of powder are not uniform across different particle sizes. The remanence and maximum magnetic energy products of samples with a particle size of 120 µm are 14.0 kGs and 41.35 MGOe, while the products of samples with a particle size of 60 µm are only 13.3 kGs and 36.31 MGOe. The macroscopic morphology of HDDR Nd2Fe14B particles and the gradient distribution of microstructures in different micro-regions were observed. By modifying the macroscopic morphology of the particles, the poorly oriented clusters on the surface of the particles were precisely eliminated, and the remanence and maximum magnetic energy products of the particles increased to 14.5 kGs and 45 MGOe, respectively. Compared with the original particles, the samples after mechanical grinding had better grain arrangement. The effects of the nanocrystalline c-axis and field misalignment angle θ on the magnetic properties of HDDR Nd2Fe14B particles were investigated through micromagnetic simulation. The targeted removal of macroscopic defects on the particle surface contributed to a 3.6% increase in remanence and an 8.8% increase in the maximum magnetic energy product, offering a promising approach to enhance the microstructure of high-performance HDDR Nd2Fe14B particles.

Assessing the performance of methods for central statistical monitoring of a binary or continuous outcome in multi-center trials: A simulation study.

BACKGROUND: Quality study monitoring is fundamental to patient safety and data integrity. Regulators and industry consortia have increasingly advocated for risk-based monitoring (RBM) and central statistical monitoring (CSM) for more effective and efficient monitoring. Assessing which statistical methods underpin these approaches can best identify unusual data patterns in multi-center clinical trials that may be driven by potential systematic errors is important. METHODS: We assessed various CSM techniques, including cross-tests, fixed-effects, mixed-effects, and finite mixture models, across scenarios with different sample sizes, contamination rates, and overdispersion via simulation. Our evaluation utilized threshold-independent metrics such as the area under the curve (AUC) and average precision (AP), offering a fuller picture of CSM performance. RESULTS: All CSM methods showed consistent characteristics across center sizes or overdispersion. The adaptive finite mixture model outperformed others in AUC and AP, especially at 30% contamination, upholding high specificity unless converging to a single-component model due to low contamination or deviation. The mixed-effects model performed well at lower contamination rates. However, it became conservative in specificity and exhibited declined performance for binary outcomes under high deviation. Cross-tests and fixed-effects methods underperformed, especially when deviation increased. CONCLUSION: Our evaluation explored the merits and drawbacks of multiple CSM methods, and found that relying on sensitivity and specificity alone is likely insufficient to fully measure predictive performance. The finite mixture method demonstrated more consistent performance across scenarios by mitigating the influence of outliers. In practice, considering the study-specific costs of false positives/negatives with available resources for monitoring is important.

Good Statistical Monitoring: A Flexible Open-Source Tool to Detect Risks in Clinical Trials.

BACKGROUND: Risk-based quality management is a regulatory-recommended approach to manage risk in a clinical trial. A key element of this strategy is to conduct risk-based monitoring to detect potential risks to critical data and processes earlier. However, there are limited publicly available tools to perform the analytics required for this purpose. Good Statistical Monitoring is a new open-source solution developed to help address this need. METHODS: A team of statisticians, data scientists, clinicians, data managers, clinical operations, regulatory, and quality compliance staff collaborated to design Good Statistical Monitoring, an R package, to flexibly and efficiently implement end-to-end analyses of key risks. The package currently supports the mapping of clinical trial data from a variety of formats, evaluation of 12 key risk indicators, interactive visualization of analysis results, and creation of standardized reports. RESULTS: The Good Statistical Monitoring package is freely available on GitHub and empowers clinical study teams to proactively monitor key risks. It employs a modular workflow to perform risk assessments that can be customized by replacing any workflow component with a study-specific alternative. Results can be exported to other clinical systems or can be viewed as an interactive report to facilitate follow-up risk mitigation. Rigorous testing and qualification are performed as part of each release to ensure package quality. CONCLUSIONS: Good Statistical Monitoring is an open-source solution designed to enable clinical study teams to implement statistical monitoring of critical risks, as part of a comprehensive risk-based quality management strategy.

Highly water-resistant paper via infiltration with polymeric microspheres from nanocellulose-stabilized plant oil-derived monomer.

Sustainable strategies to improve the water resistance of cellulose paper are actively sought. In this work, polymeric microspheres (PMs), prepared through emulsion polymerization of cellulose nanofibers stabilized rubber seed oil-derived monomer, were investigated as coatings on corrugated medium paper (CMP). After infiltrating porous paper with PMs, the water-resistant corrugated papers (WRCPn) with enhanced mechanical properties were obtained. When 30 wt% PMs were introduced, WRCP30 turned out to be highly compacted with an increased water contact angle of 106.3° and a low water vapor transmission rate of 81 g/(m2 d) at 23 °C. Meanwhile, the tensile strength of WRCP30 increased to 22.2 MPa, a 4-fold increase from CMP. When tested in a well-hydrated state, 71% of its mechanical strength in the dry state was maintained. Even with a low content of 10 wt% PMs, WRCP10 also exhibited stable tensile strength and water wettability during the cyclic soaking-drying process. Thus, the plant oil based sustainable emulsion polymers provide a convenient route for enhancing the overall performance of cellulose paper.

A wideband, high-resolution vector spectrum analyzer for integrated photonics.

The analysis of optical spectra-emission or absorption-has been arguably the most powerful approach for discovering and understanding matter. The invention and development of many kinds of spectrometers have equipped us with versatile yet ultra-sensitive diagnostic tools for trace gas detection, isotope analysis, and resolving hyperfine structures of atoms and molecules. With proliferating data and information, urgent and demanding requirements have been placed today on spectrum analysis with ever-increasing spectral bandwidth and frequency resolution. These requirements are especially stringent for broadband laser sources that carry massive information and for dispersive devices used in information processing systems. In addition, spectrum analyzers are expected to probe the device's phase response where extra information is encoded. Here we demonstrate a novel vector spectrum analyzer (VSA) that is capable of characterizing passive devices and active laser sources in one setup. Such a dual-mode VSA can measure loss, phase response, and dispersion properties of passive devices. It also can coherently map a broadband laser spectrum into the RF domain. The VSA features a bandwidth of 55.1 THz (1260-1640 nm), a frequency resolution of 471 kHz, and a dynamic range of 56 dB. Meanwhile, our fiber-based VSA is compact and robust. It requires neither high-speed modulators and photodetectors nor any active feedback control. Finally, we employ our VSA for applications including characterization of integrated dispersive waveguides, mapping frequency comb spectra, and coherent light detection and ranging (LiDAR). Our VSA presents an innovative approach for device analysis and laser spectroscopy, and can play a critical role in future photonic systems and applications for sensing, communication, imaging, and quantum information processing.

Association of serum five heavy metals level with all-cause and cause-specific mortality: a large population-based cohort study.

The study aimed to explore the association between five heavy metals exposure (Cadmium, Lead, Mercury, Manganese, and Selenium) and mortality [all-cause, cardiovascular disease (CVD), and cancer-related]. We integrated the data into the National Health and Nutrition Examination Survey from 2011 to 2018 years. A total of 16,092 participants were recruited. The link between heavy metals exposure and mortality was analyzed by constructing a restricted cubic spline (RCS) curve, Cox proportional hazard regression model, and subgroup analysis. The RCS curve was used to show a positive linear relationship between Cadmium, Lead, and all-cause mortality. In contrast, there was a negative linear correlation between Mercury and all-cause mortality. Additionally, Manganese and Selenium also had a J-shaped and L-shaped link with all-cause mortality. The positive linear, positive linear, negative liner, J-shaped, and L-shaped relationships were observed for Cadmium, Lead, Mercury, Manganese, and Selenium and CVD mortality, respectively. Cadmium, Lead, Mercury, and Selenium were observed to exhibit positive linear, U-shaped, negative linear, and L-shaped relationships with cancer-related mortality, respectively. There was an increase and then a decrease in the link between Manganese and cancer-related morality. This study revealed the correlation between the content of different elements and different types of mortality in the U.S. general population.

Autonomous Underwater Self-Healable Adhesive Elastomers Enabled by Dynamical Hydrophobic Phase-Separated Microdomains.

High-efficient underwater self-healing materials with reliable mechanical attributes hold great promise for applications in ocean explorations and diverse underwater operations. Nevertheless, achieving these functions in aquatic environments is challenging because the recombination of dynamic interactions will suffer from resistance to interfacial water molecules. Herein, an ultra-robust and all-environment stable self-healable polyurethane-amide supramolecular elastomer is developed through rational engineering of hydrophobic domains and multistrength hydrogen bonding interactions to provide mechanical and healing compatibility as well as efficient suppression of water ingress. The coupling of hydrophobic chains and hierarchical hydrogen bonds within a multiphase matrix self-assemble to generate dynamical hydrophobic hard-phase microdomains, which synergistically realize high stretchability (1601%), extreme toughness (87.1 MJ m-3), and outstanding capability to autonomous self-healing in various harsh aqueous conditions with an efficiency of 58% and healed strength of 12.7 MPa underwater. Furthermore, the self-aggregation of hydrophobic clusters with sufficient dynamic interactions endows the resultant elastomer with effective instantaneous adhesion (6.2 MPa, 941.9 N m-1) in extremely harsh aqueous conditions. It is revealed that the dynamical hydrophobic hard-phase microdomain composed of hydrophobic barriers and cooperative reversible interactions allows for regulating its mechanical enhancement and underwater self-healing efficiency, enabling the elastomers as intelligent sealing devices in marine applications.

Superelastic and superflexible cellulose aerogels for thermal insulation and oil/water separation.

Aerogels with low thermal conductivity and high adsorption capacity present a promising solution to curb water pollution caused by organic reagents as well as mitigate heat loss. Although aerogels exhibiting good adsorption capacity and thermal insulation have been reported, materials with mechanical integrity, high flexibility and shear resistance still pose a formidable task. Here, we produced bacterial cellulose-based ultralight multifunctional hybrid aerogels by using freeze-drying followed by chemical vapor deposition silylation method. The hybrid aerogels displayed a low density of 10-15 mg/cm3, high porosity exceeding 99.1 %, low thermal conductivity (27.3-29.2 mW/m.K) and superior hydrophobicity (water contact angle>120o). They also exhibited excellent mechanical properties including superelasticity, high flexibility and shear resistance. The hybrid aerogels demonstrated high heat shielding efficiency when used as an insulating material. As a selective oil absorbent, the hybrid aerogels exhibit a maximum adsorption capacity of up to approximately 156 times its own weight and excellent recoverability. Especially, the aerogel's highly accessible porous microstructure results in an impressive flux rate of up to 162 L/h.g when used as a filter in a continuous oil-water separator to isolate n-hexane-water mixtures. This work presents a novel endeavor to create high-performance, sustainable, reusable, and adaptable multifunctional aerogels.

Lower heart rate variability is associated with loss of muscle mass and sarcopenia in community-dwelling older Chinese adults.

BACKGROUND/PURPOSE: Autonomic nervous system (ANS) disorders may occur in skeletal muscle disease, but the link between them has not been fully established. Studying the relationship between them may yield insights into the mechanisms and treatment of disease. This study aimed to explore the association between heart rate variability (HRV), sarcopenia, and subscales of sarcopenia (muscle mass, muscle strength, and physical mobility). METHODS: 2514 community-dwelling older Chinese participants were included in this study. The Asian Working Group for Sarcopenia guidelines were used to define sarcopenia. HRV was measured by 90-s electrocardiogram RR interval data. All HRV parameters were transformed using natural logarithms. Multiple regression analysis and multivariate linear regression was performed using potential correlates. RESULTS: The overall prevalence of sarcopenia was 15.1 % (18.5 % in males and 12.6 % in females). In the logistic regression analysis model, there was a significant association between log-transformed standard deviation of RR interval (lnSDNN) (OR = 0.736, p = 0.019), log-transformed coefficient of variation of RR intervals (lnCVRR) (OR = 0.751, p = 0.020), log-transformed low-frequency power (lnLF) (OR = 0.861, p = 0.008), log-transformed high-frequency power (lnHF) (OR = 0.864, p = 0.003) and sarcopenia in the general population after adjusting for age, sex, body mass index (BMI), daily activity levels, hypertension, heart disease and cardiac drugs. In addition, in multivariate linear regression, lnSDNN (ß = 0.146, p = 0.001), lnCVRR (ß = 0.120, p = 0.010), lnLF (ß = 0.066, p = 0.002) and lnHF (ß = 0.065, p < 0.001) remained significantly positively associated with muscle mass, but there were no significant differences in grip strength and walking speed. CONCLUSIONS: Sarcopenia was independently associated with lower heart rate variability in a community-dwelling elderly Chinese population. In addition, muscle mass was positively associated with heart rate variability in the elderly.

Pure Laparoscopic Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) for a Giant Hepatocellular Carcinoma (> 15 cm) Abutting the Liver Hilum.

INTRODUCTION: This video manuscript presents a unique case of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure performed in case of a giant hepatocellular carcinoma (> 15 cm in size) whereby both stages were completed via the pure laparoscopic approach. METHODS: This case was performed in our institution in 2022. All data were obtained from the patient's records in our prospectively maintained database. Institutional Review Board (IRB) was not required for this publication. RESULTS: A 67-year-old Chinese male with a history of chronic hepatitis B infection presented with a giant liver mass. Magnetic resonance imaging (MRI) scan demonstrated a tumour, with features compatible with hepatocellular carcinoma, measuring 15.4 cm in maximal diameter in the right lobe of the cirrhotic liver with no distal metastasis. The indocyanine green (ICG) retention test at 15 min was prolonged at 25.5%, and the CT volumetry showed a borderline future liver remnant (FLR) volume of 692 ml or 22.9% (based on measured volume) and a standardized FLR of 49%. Stage 1 ALPPS was successfully completed via the pure laparoscopic approach. He was well post-operatively, and a repeat CT volumetry at 7 days showed an increase in FLR to 826 ml, and the ICG retention test improved to 18.1%. The patient underwent pure laparoscopic second-stage ALPPS, 8 days later. The patient recovered well with no liver decompensation or local complications. CONCLUSION: The use of MIS for in 2-stage ALPPS procedure for giant HCCs larger than 10 cm is technically feasible and safe when attempted in high-volume centres by experienced surgeons, while benefiting from the advantages of MIS liver resection.

The duration of estrogen treatment before progesterone application does not affect neonatal and perinatal outcomes in frozen embryo transfer cycles.

Objective: To explore whether the duration of estrogen treatment before progesterone application affects neonatal and perinatal outcomes in artificial frozen embryo transfer (FET) cycles. Methods: This was a retrospective cohort study. Patients who underwent FET via artificial cycles and delivered a singleton live birth between January 2015 and August 2019 were included in the analysis. According to the duration of estrogen treatment before progesterone application, we divided the cycles into four groups: ①≤12 days, ②13-15 days, ③16-19 days, and ④≥20 days. The '≤12 days group' was considered the reference group. The main outcome measures were preterm birth (PTB), small-for-gestational age (SGA), low birth weight (LBW), macrosomia, large-for-gestational age (LGA), gestational diabetes mellitus (GDM), gestational hypertension, premature rupture and placenta previa. Results: Overall, 2010 FET cycles with singleton live births were included for analysis. Cycles were allocated to four groups according to the duration of estrogen treatment before progesterone application: ①≤12 days (n=372), ②13-15 days (n=745), ③16-19 days (n=654), ④≥20 days (n=239). The neonatal outcomes, including PTB, SGA, LBW, macrosomia and LGA, were comparable among the groups (P=0.328, P=0.390, P=0.551, P=0.565, P=0.358). The rates of gestational hypertension, premature rupture and placenta previa (P=0.676, P=0.662, P=0.211) were similar among the groups. The rates of GDM among the four groups were 4.0% (15/372), 6.7% (50/745), 6.4% (42/654), and 11.3% (27/239), with statistical significance (P=0.006). After multiple logistic regression analysis, the duration of estrogen treatment did not affect the rate of GDM or other outcomes. Conclusion: The estrogen treatment duration before progesterone application does not affect neonatal and perinatal outcomes in single frozen blastocyst transfer cycles.

Baricitinib in juvenile idiopathic arthritis: an international, phase 3, randomised, double-blind, placebo-controlled, withdrawal, efficacy, and safety trial.

BACKGROUND: Juvenile idiopathic arthritis can be refractory to some or all treatment regimens, therefore new medications are needed to treat this population. This trial assessed the efficacy and safety of baricitinib, an oral Janus kinase 1/2-selective inhibitor, versus placebo in patients with juvenile idiopathic arthritis. METHODS: This phase 3, randomised, double-blind, placebo-controlled, withdrawal, efficacy, and safety trial was conducted in 75 centres in 20 countries. We enrolled patients (aged 2 to <18 years) with polyarticular juvenile idiopathic arthritis (positive or negative for rheumatoid factor), extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, or juvenile psoriatic arthritis, and an inadequate response (after ≥12 weeks of treatment) or intolerance to one or more conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). The trial consisted of a 2-week safety and pharmacokinetic period, a 12-week open-label lead-in period (10 weeks for the safety and pharmacokinetic subcohort), and an up to 32-week placebo-controlled double-blind withdrawal period. After age-based dosing was established in the safety and pharmacokinetic period, patients received a once-daily 4 mg adult-equivalent dose of baricitinib (tablets or suspension) in the open-label lead-in period. Patients meeting Juvenile Idiopathic Arthritis-American College of Rheumatology (JIA-ACR) 30 criteria (JIA-ACR30 responders) at the end of the open-label lead-in (week 12) were eligible for random assignment (1:1) to receive placebo or continue receiving baricitinib, and remained in the double-blind withdrawal period until disease flare or up to the end of the double-blind withdrawal period (week 44). Patients and any personnel interacting directly with patients or sites were masked to group assignment. The primary endpoint was time to disease flare during the double-blind withdrawal period and was assessed in the intention-to-treat population of all randomly assigned patients. Safety was assessed in all patients who received at least one dose of baricitinib throughout the three trial periods. For adverse events in the double-blind withdrawal period, exposure-adjusted incidence rates were calculated. The trial was registered on ClinicalTrials.gov, NCT03773978, and is completed. FINDINGS: Between Dec 17, 2018 and March 3, 2021, 220 patients were enrolled and received at least one dose of baricitinib (152 [69%] girls and 68 [31%] boys; median age 14·0 years [IQR 12·0-16·0]). 219 patients received baricitinib in the open-label lead-in period, of whom 163 (74%) had at least a JIA-ACR30 response at week 12 and were randomly assigned to placebo (n=81) or baricitinib (n=82) in the double-blind withdrawal period. Time to disease flare was significantly shorter with placebo versus baricitinib (hazard ratio 0·241 [95% CI 0·128-0·453], p<0·0001). Median time to flare was 27·14 weeks (95% CI 15·29-not estimable) in the placebo group, and not evaluable for patients in the baricitinib group (<50% had a flare event). Six (3%) of 220 patients had serious adverse events during the safety and pharmacokinetic period or open-label lead-in period. In the double-blind withdrawal period, serious adverse events were reported in four (5%) of 82 patients (incidence rate [IR] 9·7 [95% CI 2·7-24·9] per 100 patient-years at risk) in the baricitinib group and three (4%) of 81 (IR 10·2 [2·1-29·7]) in the placebo group. Treatment-emergent infections were reported during the safety and pharmacokinetic or open-label lead-in period in 55 (25%) of 220 patients, and during the double-blind withdrawal period in 31 (38%) of 82 (IR 102·1 [95% CI 69·3-144·9]) in the baricitinib group and 15 (19%) of 81 (IR 59·0 [33·0-97·3]) in the placebo group. Pulmonary embolism was reported as a serious adverse event in one patient (1%; IR 2·4 [95% CI 0·1-13·3]) in the baricitinib group in the double-blind withdrawal period, which was judged to be related to study treatment. INTERPRETATION: Baricitinib was efficacious with an acceptable safety profile in the treatment of polyarticular juvenile idiopathic arthritis, extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, and juvenile psoriatic arthritis, after inadequate response or intolerance to standard therapy. FUNDING: Eli Lilly and Company under licence from Incyte.

Efficacy, feasibility and safety of TIPS in the treatment of recurrent portal hypertension with variceal bleeding after open splenectomy and esophagogastric devascularization.

PURPOSE: To investigate the efficacy, feasibility, and safety of transjugular intrahepatic portosystemic shunt (TIPS) as a treatment for patients with recurrent portal hypertension with variceal bleeding (RPHVB) who have previously undergone open splenectomy and esophagogastric devascularization (OSED). METHODS: The data were retrospectively retrieved from 39 cirrhotic RPHVB patients who had undergone OSED from August 2015 to December 2020. All patients were treated with TIPS using the Viabahn stent. RESULTS: Out of the 39 patients included in the study, TIPS was successfully performed in 38 patients with a success rate of 97.44%. One patient had a failed attempt due to cavernous transformation of the portal vein (CTPV). Among the 38 patients who underwent TIPS, 33 patients also underwent varicose vein embolization, while the remaining 5 patients only underwent TIPS procedure. A total of 39 Viabahn stents were implanted, with 5 patients receiving stents expanded to their nominal diameter of 8 mm and the remaining 33 patients having their shunt maintained at a diameter of 6 mm. The postoperative hemostasis rate was 97.37% (37/38). The portal vein pressure (PVP) and portal pressure gradient (PPG) decreased significantly from (31.28 ± 6.24) and (20.61 ± 5.14) mmHg to (19.58 ± 4.69) and (9.24 ± 3.07) mmHg, respectively (P < 0.001). During the follow-up period, the rebleeding rate was 6.09% (2/29), while the incidence of hepatic encephalopathy (HE) and shunt dysfunction was 13.79% (4/29) for each. CONCLUSION: Transjugular intrahepatic portosystemic shunt is an effective, feasible and safe treatment for RPHVB patients who have previously undergone OSED. A satisfactory clinical outcome could be achieved with a 6 mm-diameter shunt in most patients.

Thiol-Aldehyde Polycondensation for Bio-based Adaptable and Degradable Phenolic Polymers.

Designing sustainable materials with tunable mechanical properties, intrinsic degradability, and recyclability from renewable biomass through a mild process has become vital in polymer science. Traditional phenolic resins are generally considered to be not degradable or recyclable. Here we report the design and synthesis of linear and network structured phenolic polymers using facile polycondensation between natural aldehyde-bearing phenolic compounds and polymercaptans. Linear phenolic products are amorphous with Tg between -9 °C and 12 °C. Cross-linked networks from vanillin and its di-aldehyde derivative exhibited excellent mechanical strength between 6-64 MPa. The connecting dithioacetals are associatively adaptable strong bonds and susceptible to degradation in oxidative conditions to regenerate vanillin. These results highlight the potential of biobased sustainable phenolic polymers with recyclability and selective degradation, as a complement to the traditional phenol-formaldehyde resins.

The HIF-1α/miR-26a-5p/PFKFB3/ULK1/2 axis regulates vascular remodeling in hypoxia-induced pulmonary hypertension by modulation of autophagy.

Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease characterized by pulmonary vascular remodeling, which may cause right heart failure and even death. Accumulated evidence confirmed that microRNA-26 family play critical roles in cardiovascular disease; however, their function in PAH remains largely unknown. Here, we investigated the expression of miR-26 family in plasma from PAH patients using quantitative RT-PCR, and identified miR-26a-5p as the most downregulated member, which was also decreased in hypoxia-induced pulmonary arterial smooth muscle cell (PASMC) autophagy models and lung tissues of PAH patients. Furthermore, chromatin immunoprecipitation (ChIP) analysis and luciferase reporter assays revealed that hypoxia-inducible factor 1α (HIF-1α) specifically interacted with the promoter of miR-26a-5p and inhibited its expression in PASMCs. Tandem mRFP-GFP-LC3B fluorescence microscopy demonstrated that miR-26a-5p inhibited hypoxia-induced PAMSC autophagy, characterized by reduced formation of autophagosomes and autolysosomes. In addition, results showed that miR-26a-5p overexpression potently inhibited PASMC proliferation and migration, as determined by cell counting kit-8, EdU staining, wound-healing, and transwell assays. Mechanistically, PFKFB3, ULK1, and ULK2 were direct targets of miR-26a-5p, as determined by dual-luciferase reporter gene assays and western blots. Meanwhile, PFKFB3 could further enhance the phosphorylation level of ULK1 and promote autophagy in PASMCs. Moreover, intratracheal administration of adeno-miR-26a-5p markedly alleviated right ventricular hypertrophy and pulmonary vascular remodeling in hypoxia-induced PAH rat models in vivo. Taken together, the HIF-1α/miR-26a-5p/PFKFB3/ULK1/2 axis plays critical roles in the regulation of hypoxia-induced PASMC autophagy and proliferation. MiR-26a-5p may represent as an attractive biomarker for the diagnosis and treatment of PAH.