Increased Epstein‒Barr virus reactivation following prophylaxis for cytomegalovirus infection after haploidentical haematopoietic stem cell transplantation.

Letermovir (LTV) prophylaxis is effective in reducing the incidence of clinically significant cytomegalovirus (CMV) infection (cs CMVi) after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Since our centre began administering LTV prophylaxis in June 2022, we have observed a certain increase in the incidence of Epstein-Barr virus (EBV) reactivation after haploidentical HSCT. We retrospectively analysed 230 consecutive patients who underwent haploidentical HSCT with rabbit anti-thymocyte globulin (ATG) from October 2022 to June 2023. The LTV group included 133 patients who received LTV prophylaxis, and the control group included 97 patients who did not receive LTV prophylaxis. At 1 year after HSCT, EBV reactivation was observed in 36 patients (27%) in the LTV group and 13 patients (13%) in the control group (p = 0.012). All patients with EBV reactivation had EBV-DNAemia, and one patient in each group developed EBV-associated posttransplantation lymphoproliferative disorder (PTLD). The proportion of patients with low EBV-DNA loads (> 5 × 102 to < 1 × 104 copies/mL) was greater in the LTV group than in the control group (23% vs. 10%, p = 0.01). The proportion of patients with CMV reactivation was lower in the LTV group than in the control group (35% vs. 56%, p = 0.002). There was no significant difference between the groups in terms of neutrophil and platelet count recovery, the cumulative incidence of acute/chronic graft-versus-host disease, overall survival, cumulative relapse rate or nonrelapse mortality. Our results show that the increased incidence of EBV reactivation may be associated with LTV prophylaxis for CMV after haploidentical HSCT.

Astragalus polysaccharide (APS) improves the immune function in diet-induced obese (DIO) mice.

Obesity is a major health hazard, suppressing the immune system and complicating inflammatory symptoms treatment. Traditional Chinese medicine emphasizes holistic principles and syndrome-based diagnosis/therapy. Its primary focus is on enhancing overall well-being, rather than solely aiming for weight loss. Astragalus polysaccharide (APS), extracted from Astragalus membranaceus, has demonstrated promising effects in enhancing the health status of obese individuals. Therefore, this study employed DIO mouse model to explore the immunomodulatory effects of APS in obese mice. The findings revealed a dose-dependent effect of APS on obesity prevention in DIO mice. Specifically, a 4% concentration of APS significantly reduced body weight, whereas a 2% concentration tended to increase it. Furthermore, APS effectively modulated blood glucose and lipid profiles, demonstrating varying degrees of improvement in blood glucose and blood lipid-related factors. Notably, APS also facilitated the reactivation of suppressed immune function in obese mice, regulating a range of immunological variables associated with obesity and thereby maintaining homeostasis. In conclusion, the functional benefits of APS were dose-related, with a 4% concentration demonstrating promising results in obesity prevention and immune system modulation. These findings provide a potential reference for treating inflammatory conditions associated with obesity, contributing academic understanding of obesity management and immunomodulation.

A Superior Bifunctional Electrocatalyst in Which Directional Electron Transfer Occurs Between a Co/Ni Alloy and Fe─N─C Support.

Stable, efficient, and economical bifunctional electrocatalysts for oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) are needed for rechargeable Zn-air batteries. In this study, a directional electron transfer pathway is exploited in a spatial heterojunction of CoyNix@Fe─N─C heterogeneous catalyst for effective bifunctional electrolysis (OER/ORR). Thereinto, the Co/Ni alloy is strongly coupled to the Fe─N─C support through Co/Ni─N bonds. DFT calculations and experimental findings confirm that Co/Ni─N bonds play a bridging role in the directional electron transfer from Co/Ni alloy to the Fe─N─C support, increasing the content of pyridinic nitrogen in the ORR-active support. In addition, the discovered directional electron transfer mechanism enhances both the ORR/OER activity and the durability of the catalyst. The Co0.66Ni0.34@Fe─N─C with the optimal Ni/Co ratio exhibits satisfying bifunctional electrocatalytic performance, requiring an ORR half-wave potential of 0.90 V and an OER overpotential of 317 mV at 10 mA cm-2 in alkaline electrolytes. The assembled rechargeable zinc-air batteries (ZABs) incorporating Co0.66Ni0.34@Fe─N─C cathode exhibits a charge-discharge voltage gap comparable to the Pt/C||IrO2 assembly and high robustness for over 60 h at 20 mA cm-2.

TRIM26 deficiency enhancing liver regeneration through macrophage polarization and ß-catenin pathway activation.

Liver regeneration is a complex process involving the crosstalk between parenchymal and non-parenchymal cells, especially macrophages. However, the underlying mechanisms remain incompletely understood. Here, we identify the E3 ubiquitin ligase TRIM26 as a crucial regulator of liver regeneration. Following partial hepatectomy or acute liver injury induced by carbon tetrachloride, Trim26 knockout mice exhibit enhanced hepatocyte proliferation compared to wild-type controls, while adeno-associated virus (AAV)-mediated overexpression of Trim26 reverses the promotional effects. Mechanistically, Trim26 deficiency promotes the recruitment of macrophages to the liver and their polarization towards pro-inflammatory M1 phenotype. These M1 macrophages secrete Wnts, including Wnt2, which subsequently stimulate hepatocyte proliferation through the activation of Wnt/ß-catenin signaling. In hepatocytes, Trim26 knockdown reduces the ubiquitination and degradation of ß-catenin, thereby further enhancing Wnt/ß-catenin signaling. Pharmacological inhibition of Wnt/ß-catenin pathway by ICG-001 or depletion of macrophages by clodronate liposomes diminishes the pro-regenerative effects of Trim26 deficiency. Moreover, bone marrow transplantation experiments provide evidence that Trim26 knockout in myeloid cells alone can also promote liver regeneration, highlighting the critical role of macrophage Trim26 in this process. Taken together, our study uncovers TRIM26 as a negative regulator of liver regeneration by modulating macrophage polarization and Wnt/ß-catenin signaling in hepatocytes, providing a potential therapeutic target for promoting liver regeneration in clinical settings.

Early-Age Cracking of Fly Ash and GGBFS Concrete Due to Shrinkage, Creep, and Thermal Effects: A Review.

Supplementary cementitious materials (SCMs) are eco-friendly cementitious materials that can partially replace ordinary Portland cement (OPC). The occurrence of early-age cracking in OPC-SCM blended cement is a significant factor impacting the mechanical properties and durability of the concrete. This article presents a comprehensive review of the existing research on cracking in OPC-SCM concrete mix at early ages. To assess the effects of SCMs on the early-age cracking of concrete, the properties of blended cement-based concrete, in terms of its viscoelastic behavior, evolution of mechanical performance, and factors that affect the risk of cracking in concrete at early ages, are reviewed. The use of SCMs in OPC-SCM concrete mix can be an effective method for mitigating early-age cracking while improving the properties and durability of concrete structures. Previous research showed that the shrinkage and creep of OPC-SCM concrete mix are lower than those of conventional concrete. Moreover, the lower cement content of OPC-SCM concrete mix resulted in a better resistance to thermal cracking. Proper selection, proportioning, and implementation of SCMs in concrete can help to optimize the performance and reduce the environmental impact of OPC-SCM concrete mix.

Lipid-lowering, antihypertensive, and antithrombotic effects of nattokinase combined with red yeast rice in patients with stable coronary artery disease: a randomized, double-blinded, placebo-controlled trial.

Nattokinase (NK) and red yeast rice (RYR) are both indicated for their potential in cardiovascular disease prevention and management, but their combined effects especially in coronary artery disease (CAD) are scarcely examined. This 90-day randomized, double-blind trial aims to investigate the effect of NK and RYR supplementations on cardiometabolic parameters in patients with stable CAD. 178 CAD patients were randomized to four groups: NK + RYR, NK, RYR, and placebo. No adverse effects due to the interventions were reported. In comparisons across groups, NK + RYR showed the maximum effect in reducing triglyceride (-0.39 mmol), total cholesterol (-0.66 mmol/L), diastolic blood pressure (-7.39 mmHg), and increase in high-density lipoprotein cholesterol (0.195 mmol/L) than other groups (all p for multiple groups comparison<0.01). Both NK + RYR and NK groups had significantly better-improved lactate dehydrogenase than the others (-29.1 U/L and - 26.4 U/L). NK + RYR group also showed more potent reductions in thromboxane B2 and increases in antithrombin III compared to placebo (both p < 0.01). These improved markers suggest that combined NK and RYR may preferably alter antithrombin and COX-1 pathways, potentially reducing thrombosis risks in CAD patients. Overall, the combined NK and RYR supplementation is safe and more effective than separately in improving cardiometabolic markers among CAD patients with multiple heart medications use.

Screening for exclusion of high-risk bleeding features of esophageal varices in cirrhosis through CT and MRI.

BACKGROUND & AIM: Esophageal varices (EV) screening guidelines have evolved with improved risk stratification to avoid unnecessary esophagogastroduodenoscopy (EGD) in individuals with low bleeding risks. However, uncertainties persist in the recommendations for certain patient groups, particularly those with hepatocellular carcinoma (HCC) and/or receiving non-selective beta-blockers (NSBB) without prior endoscopy. This study assessed the efficacy of imaging in ruling out EVs and their high-risk features associated with bleeding in patients with cirrhosis and with HCC. We also evaluated the impact of NSBB on the detection of these characteristics. METHODS: A total of 119 patients undergoing EGD with CT and/or MRI within 90 days of the procedure were included. 87 patients had HCC. A new imaging grading system was developed utilizing the size of EVs and the extent of their protrusion into the esophagus lumen. The negative predictive value (NPV) of EVimaging(-) versus EVimaging (+) (grades 1-3) in ruling out the presence of EV and/or high-risk features by EGD was calculated. The predictive performance of imaging was determined by logistic regression. RESULTS: The NPV of imaging for detecting EV and high-risk features was 81 % and 92 %, respectively. Among HCC patients, the NPV for EV and high-risk features was 80 % and 64 %, respectively. Being on NSBB didn't statistically impact the imaging detection of EV. Imaging was a better predictor of high-risk EGD findings than Child-Turcotte-Pugh scores. CONCLUSIONS: Our results suggest that imaging can effectively rule out the presence of EV and high-risk features during EGD, even in patients with HCC and/or receiving NSBB.

Efficacy of third-generation epidermal growth factor receptor-tyrosine kinase inhibitors in advanced NSCLC with different T790M statuses tested via digital droplet polymerase chain reaction ddPCR and next-generation sequencing.

OBJECTIVES: We hypothesize that digital droplet polymerase chain reaction (ddPCR) would optimize the treatment strategies in epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) relapsed patients. In this study, we compared the efficacy of third-generation TKIs with various T790M statuses via ddPCR and next-generation sequencing (NGS). METHODS: NGS was performed on blood samples of patients progressed from previous EGFR-TKIs for resistance mechanism. T790M-negative patients received further liquid biopsy using ddPCR for T790M detection. RESULTS: A cohort of 40 patients were enrolled, with 30.0% (12/40) T790M-positive via NGS (Group A). In another 28 T790M-negative patients by NGS, 11 (39.3%) were T790M-positive (Group B) and 17 (60.7%) were T790M-negative (Group C) via ddPCR. A relatively longer progression-free survival (PFS) was observed in group A (NR) and group B (10.0 months, 95% CI 7.040-12.889) than in group C (7.0 months, 95% CI 0.000-15.219), with no significant difference across all three groups (p = 0.196), or between group B and C (p = 0.412). EGFR-sensitive mutation correlated with inferior PFS (p = 0.041) and ORR (p = 0.326), and a significantly lower DCR (p = 0.033) in T790M-negative patients via NGS (n = 28). CONCLUSION: This study indicates that ddPCR may contribute as a supplement to NGS in liquid biopsies for T790M detection in EGFR-TKIs relapsed patients and help to optimize the treatment strategies, especially for those without coexistence of EGFR-sensitive mutation. TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT05458726.

Organic Fluorophores with Large Stokes Shift for the Visualization of Rapid Protein and Nucleic Acid Assays.

Organic small-molecule fluorophores, characterized by flexible chemical structure and adjustable optical performance, have shown tremendous potential in biosensing. However, classical organic fluorophore motifs feature large overlap between excitation and emission spectra, leading to the requirement of advanced optical set up to filter desired signal, which limits their application in scenarios with simple settings. Here, a series of wavelength-tunable small-molecule fluorescent dyes (PTs) bearing simple organic moieties have been developed, which exhibit Stokes shift up to 262 nm, molar extinction coefficients ranged 30,000-100,000 M-1 cm-1, with quantum yields up to 54.8 %. Furthermore, these dyes were formulated into fluorescent nanoparticles (PT-NPs), and applied in lateral flow assay (LFA). Consequently, limit of detection for SARS-CoV-2 nucleocapsid protein reached 20 fM with naked eye, a 100-fold improvement in sensitivity compared to the pM detection level for colloidal gold-based LFA. Besides, combined with loop-mediated isothermal amplification (LAMP), the LFA system achieved the visualization of single copy level nucleic acid detection for monkeypox (Mpox).

Unveiling the structural mechanisms of nonpeptide ligand recognition and activation in human chemokine receptor CCR8.

The human CC chemokine receptor 8 (CCR8) is an emerging therapeutic target for cancer immunotherapy and autoimmune diseases. Understanding the molecular recognition of CCR8, particularly with nonpeptide ligands, is valuable for drug development. Here, we report three cryo-electron microscopy structures of human CCR8 complexed with Gi trimers in the ligand-free state or activated by nonpeptide agonists LMD-009 and ZK 756326. A conserved Y1.39Y3.32E7.39 motif in the orthosteric binding pocket is shown to play a crucial role in the chemokine and nonpeptide ligand recognition. Structural and functional analyses indicate that the lack of conservation in Y1143.33 and Y1724.64 among the CC chemokine receptors could potentially contribute to the selectivity of the nonpeptide ligand binding to CCR8. These findings present the characterization of the molecular interaction between a nonpeptide agonist and a chemokine receptor, aiding the development of therapeutics targeting related diseases through a structure-based approach.

A natural IgM hitchhiking strategy for delivery of cancer nanovaccines to splenic marginal zone B cells.

B cell-targeted cancer vaccines are receiving increasing attention in immunotherapy due to the combined antibody-secreting and antigen-presenting functions. In this study, we propose a natural IgM-hitchhiking delivery strategy to co-deliver tumor antigens and adjuvants to splenic marginal zone B (MZB) cells. We constructed nanovaccines (FA-sLip/OVA/MPLA) consisting of classical folic acid (FA)-conjugated liposomes co-loaded with ovalbumin (OVA) and toll-like receptor 4 agonists, MPLA. We found that natural IgM absorption could be manipulated at the bio-nano interface on FA-sLip/OVA/MPLA, enabling targeted delivery to splenic MZB cells. Systemic administration of FA-sLip/OVA/MPLA effectively activated splenic MZB cells via IgM-mediated multiplex pathways, eliciting antigen-specific humoral and cytotoxic T lymphocyte responses, and ultimately retarding E.G7-OVA tumor growth. In addition, combining FA-sLip/OVA/MPLA immunization with anti-PD-1 treatments showed improved antitumor efficiency. Overall, this natural IgM-hitchhiking delivery strategy holds great promise for efficient, splenic MZB cell-targeted delivery of cancer vaccines in future applications.

Association of the Kiwi OmniCup system with maternal and neonatal morbidity: A retrospective cohort study.

OBJECTIVE: To discuss the effect of the Kiwi OmniCup system on reducing adverse maternal and neonatal outcomes and provide a reference for assisted vaginal delivery methods. METHODS: Women who gave birth to singleton term neonates in a cephalic presentation and underwent assisted vaginal delivery from 2017 to 2021 were eligible for inclusion in the study; they were divided into a Kiwi OmniCup system group and a forceps group. Binary logistic regression analysis was used to observe and compare maternal and neonatal outcomes. The primary outcomes were severe maternal and neonatal morbidity. Severe maternal morbidity was defined as the occurrence of at least one of the following outcomes: third- or fourth-degree perineal lacerations, refractory postpartum hemorrhage, thrombotic events, amniotic fluid embolism, admission to the intensive care unit, and maternal death. Severe neonatal morbidity was defined as the occurrence of at least one of the following outcomes: neonatal asphyxia requiring resuscitation or intubation, neonatal head and face injuries, neonatal fracture, and admission to the neonatal intensive care unit for longer than 24 h. RESULTS: The rate of severe neonatal morbidity in the forceps group was significantly higher than that in the Kiwi OmniCup system group, the differences between the two groups were significant (27.2% vs. 42.3%, P < 0.001), and there was no significant difference in the rate of severe maternal morbidity between the two groups (30% vs. 30%, P > 0.05). Binary logistic regression analysis showed that Kiwi OmniCup system-assisted delivery reduced severe neonatal morbidity (adjusted odds ratio 0.49; 95% confidence interval 0.33-0.73) and did not increase severe maternal morbidity compared with forceps-assisted delivery. CONCLUSION: The Kiwi OmniCup system, which can reduce the incidence of severe neonatal morbidity without increasing the incidence of serious adverse maternal outcomes, is worthy of clinical promotion.

Electronic structure optimizing of Ru nanoclusters via Co single atom and N, S co-doped reduced graphene oxide for accelerating water electrolysis.

The development of efficient and stable electrocatalysts for hydrogen evolution reaction (HER) is impending for the advancement of water-splitting. In this study, we developed a novel electrocatalyst consisting of highly dispersed Ru nanoclusters ameliorated by cobalt single atoms and N, S co-doped reduced graphene oxide (CoSARuNC@NSG). Benefitted from the optimized electronic structure of the Ru nanoclusters induced by the adjacent single atomic Co and N, S co-doped RGO support, the electrocatalyst exhibits exceptional HER performance with overpotentials of 15 mV and 74 mV for achieving a current density of 10 mA cm-2 in alkaline and acidic water. The catalyst outperforms most noble metal-based HER electrocatalysts. Furthermore, the electrolyzer assembled with CoSARuNC@NSG and RuO2 demonstrated an overall voltage of 1.56 V at 10 mA cm-2 and an excellent operational stability for over 25 h with almost no attenuation. Theoretical calculations also deduce its high HER activity demonstrated by the smaller reaction energy barrier due to the optimized electronic structure of Ru nanoclusters. This strategy involving the regulation of metal nanoparticles activity through flexible single atom and GO support could provide valuable insights into the design of high-performance and low-cost HER catalysts.

Calculation of carbon emissions in wastewater treatment and its neutralization measures: A review.

As the pursuit of "carbon neutrality" gains momentum, the emphasis on low-carbon solutions, emphasizing energy conservation and resource reuse, has introduced fresh challenges to conventional wastewater treatment approaches. Precisely evaluating carbon emissions in urban water supply and drainage systems, wastewater treatment plants, and establishing carbon-neutral operating models has become a pivotal concern in the future of wastewater treatment. Regrettably, limited research has been devoted to carbon accounting and the development of carbon-neutral strategies for wastewater treatment. In this review, to facilitate comprehensive carbon accounting, we initially recognizes direct and indirect carbon emission sources in the wastewater treatment process. We then provide an overview of several major carbon accounting methods and propose a carbon accounting framework. Furthermore, we advocate for a systemic perspective, highlighting that achieving carbon neutrality in wastewater treatment extends beyond the boundaries of wastewater treatment plants. We assess current technical measures both within and outside the plants that contribute to achieving carbon-neutral operations. Encouraging the application of intelligent algorithms for the multifaceted monitoring and control of wastewater treatment processes is paramount. Supporting resource and energy recycling is also essential, as is recognizing the benefits of synergistic wastewater treatment technologies. We advocate a systematic, multi-level planning approach that takes into account a wide range of factors. Our goal is to offer valuable insights and support for the practical implementation of water environment management within the framework of carbon neutrality, and to advance sustainable socio-economic development and contribute to a more environmentally responsible future.

Adjuvant and neo-adjuvant immunotherapy in resectable non-small cell lung cancer (NSCLC): Current status and perspectives.

Surgery followed by adjuvant chemotherapy is the standard of care for selected patients with early-stage or locally advanced non-small cell lung cancer (NSCLC). However, many of these patients still experience postoperative recurrence at 5 years. At present, peri-operative treatment methods are emerging to prevent early relapse, such as targeted therapy and immunotherapy. Investigation on predictive biomarkers of responses to adjuvant and neoadjuvant therapies is also continuously ongoing. Immunotherapy represented by immune checkpoint inhibitors (ICIs), either by monotherapy or in combination with chemotherapy, has shown benefit in promoting pathological responses and prolonging survival for patients with NSCLC without oncogenic mutations. Exploratory studies have also provided evidence regarding the selection of patients who benefit from ICI-based perioperative treatment. This review focuses on the existing data of current clinical trials of adjuvant and neoadjuvant strategies with ICIs in resectable NSCLC, the exploration of predictive biomarkers, and the perspectives and urgent challenges in the future.

Rapid and noninvasive cell assay by microfluidic-integrated intracavity evanescent field absorption in a fiber ring laser.

BACKGROUND: Highly sensitive and rapid detection of cell concentration and interfacial molecular events is of great value for biological, biomedical, and chemical research. Most traditional biosensors require large sample volumes and complicated functional modifications of the surface. It is of great significance to develop label-free biosensor platforms with minimal sample consumption for studying cell concentration changes and interfacial molecular events without labor-intensive procedures. RESULTS: Here, a fiber-optic biosensor based on intracavity evanescent field absorption sensing is designed for sensitive and label-free cell assays for the first time. The interaction between the cells and the evanescent field is enhanced by introducing microfluidic-integrated intracavity absorption in a fiber ring laser. This strategy extends the range of targeted analytes to include quantification of a large number of targets on a surface and improves the detection sensitivity of the fiber-optic biosensor. The level of sensing resolution could be improved from 10-4 RIU to 10-7 RIU using this strategy. The stem cells were studied over a wide concentration range (from 500 to 1.2 × 105 cells/ml) and were measured sequentially. By measuring the output power of the intracavity absorption sensing system, the cell concentration can be directly determined in a label-free manner. The results show that dozens of stem cells can be sensitively detected with a sample consumption of 72 µL. The response was fast (15 s) with a low temperature cross-sensitivity of 0.031 cells·ml-1/°C. SIGNIFICANCE: The proposed method suggests its capacity for true label-free and noninvasive cell assays with a low limit of detection and small sample consumption. This has the potential to be used as a universal tool for quantitative and qualitative characterization of various cells and other biochemical analytes.

Multiplexed discrimination of SARS-CoV-2 variants via plasmonic-enhanced fluorescence in a portable and automated device.

Portable assays for the rapid identification of lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to aid large-scale efforts in monitoring the evolution of the virus. Here we report a multiplexed assay in a microarray format for the detection, via isothermal amplification and plasmonic-gold-enhanced near-infrared fluorescence, of variants of SARS-CoV-2. The assay, which has single-nucleotide specificity for variant discrimination, single-RNA-copy sensitivity and does not require RNA extraction, discriminated 12 lineages of SARS-CoV-2 (in three mutational hotspots of the Spike protein) and detected the virus in nasopharyngeal swabs from 1,034 individuals at 98.8% sensitivity and 100% specificity, with 97.6% concordance with genome sequencing in variant discrimination. We also report a compact, portable and fully automated device integrating the entire swab-to-result workflow and amenable to the point-of-care detection of SARS-CoV-2 variants. Portable, rapid, accurate and multiplexed assays for the detection of SARS-CoV-2 variants and lineages may facilitate variant-surveillance efforts.

Acetylcholine (ACh) enhances Cd tolerance through transporting ACh in vesicles and modifying Cd absorption in duckweed (Lemna turionifera 5511).

Acetylcholine (ACh), an important neurotransmitter, plays a role in resistance to abiotic stress. However, the role of ACh during cadmium (Cd) resistance in duckweed (Lemna turionifera 5511) remains uncharacterized. In this study, the changes of endogenous ACh in duckweed under Cd stress has been investigated. Also, how exogenous ACh affects duckweed's ability to withstand Cd stress was studied. The ACh sensor transgenic duckweed (ACh 3.0) showed the ACh signal response under Cd stress. And ACh was wrapped and released in vesicles. Cd stress promoted ACh content in duckweed. The gene expression analysis showed an improved fatty acid metabolism and choline transport. Moreover, exogenous ACh addition enhanced Cd tolerance and decreased Cd accumulation in duckweed. ACh supplement reduced the root abscission rate, alleviated leaf etiolation, and improved chlorophyll fluorescence parameters under Cd stress. A modified calcium (Ca2+) flux and improved Cd2+ absorption were present in conjunction with it. Thus, we speculate that ACh could improve Cd resistance by promoting the uptake and accumulation of Cd, as well as the response of the Ca2+ signaling pathway. Also, plant-derived extracellular vesicles (PDEVs) were extracted during Cd stress. Therefore, these results provide new insights into the response of ACh during Cd stress.

Glycyrrhizic Acid-Lipid Framework Nanovehicle Loading Triptolide for Combined Immunochemotherapy.

Despite the acknowledged advantages of combined immunochemotherapy for tumor treatment, the high efficiency of co-delivery of these combined agents into the targeted tumor tissue is still challenging. Herein, based on a "three-birds-with-one-stone" strategy, a facile glycyrrhizic acid (GL)-lipid hybrid nanoplatform loading triptolide (TP/GLLNP) is designed to better address the dilemma. Differing from the traditional liposomes with dual-drug co-delivery NPs, GL with a cholesterol-like structure is primarily employed to construct the lipid membrane skeleton of the GL-based lipid nanoparticle (GLLNP), and then triptolide (TP) is readily loaded in the lipid bilayer of GLLNP. The fabricated GLLNP possessed similar drug loading efficacy, particle size, and storage stability; none of the hemolysis; even higher membrane fluidity; and lower absorbed opsonin proteins compared with the conventional liposomes. Compared to TP-loaded traditional liposomes (TP/Lipo), TP/GLLNP exhibits significantly enhanced cellular uptake, cytotoxicity, and apoptosis of HepG2 cells. In addition, GLLNP could ameliorate tumor immunosuppression by promoting tumor-associated macrophage polarization from M2 to M1 phenotype. Furthermore, enhanced retention and accumulation in the tumor area of GLLNP could be found. As expected, TP/GLLNP displayed synergistic anti-hepatocellular carcinoma efficacy in vivo. In conclusion, this study provides an inspirational strategy to combine the anti-HCC benefits of GL and TP using a novel dual-drug co-delivery nanosystem.

Polyelectrolyte elastomer-based ionotronic sensors with multi-mode sensing capabilities via multi-material 3D printing.

Stretchable ionotronics have drawn increasing attention during the past decade, enabling myriad applications in engineering and biomedicine. However, existing ionotronic sensors suffer from limited sensing capabilities due to simple device structures and poor stability due to the leakage of ingredients. In this study, we rationally design and fabricate a plethora of architected leakage-free ionotronic sensors with multi-mode sensing capabilities, using DLP-based 3D printing and a polyelectrolyte elastomer. We synthesize a photo-polymerizable ionic monomer for the polyelectrolyte elastomer, which is stretchable, transparent, ionically conductive, thermally stable, and leakage-resistant. The printed sensors possess robust interfaces and extraordinary long-term stability. The multi-material 3D printing allows high flexibility in structural design, enabling the sensing of tension, compression, shear, and torsion, with on-demand tailorable sensitivities through elaborate programming of device architectures. Furthermore, we fabricate integrated ionotronic sensors that can perceive different mechanical stimuli simultaneously without mutual signal interferences. We demonstrate a sensing kit consisting of four shear sensors and one compressive sensor, and connect it to a remote-control system that is programmed to wirelessly control the flight of a drone. Multi-material 3D printing of leakage-free polyelectrolyte elastomers paves new avenues for manufacturing stretchable ionotronics by resolving the deficiencies of stability and functionalities simultaneously.