Asymmetric Assembly in Microdroplets: Efficient Construction of MOF Micromotors for Anti-Gravity Diffusion.

Janus-micromotors, as efficient self-propelled materials, have garnered considerable attention for their potential applications in non-agitated liquids. However, the design of micromotors is still challenging and with limited approaches, especially concerning speed and mobility in complex environments. Herein, a two-step spray-drying approach encompassing symmetrical assembly and asymmetrical assembly is introduced to fabricate the metal-organic framework (MOF) Janus-micromotors with hierarchical pores. Using a spray-dryer, a symmetrical assembly is first employed to prepare macro-meso-microporous UiO-66 with intrinsic micropores (<0.5 nm) alongside mesopores (≈24 nm) and macropores (≈400 nm). Subsequent asymmetrical assembly yielded the UiO-66-Janus loaded with the reducible nanoparticles, which underwent oxidation by KMnO4 to form MnO2 micromotors. The micromotors efficiently generated O2 for self-propulsion in H2O2, exhibiting ultrahigh speeds (1135 µm s-1, in a 5% H2O2 solution) and unique anti-gravity diffusion effects. In a specially designed simulated sand-water system, the micromotors traversed from the lower water to the upper water through the sand layer. In particular, the as-prepared micromotors demonstrated optimal efficiency in pollutant removal, with an adsorption kinetic coefficient exceeding five times that of the micromotors only possessing micropores and mesopores. This novel strategy fabricating Janus-micromotors shows great potential for efficient treatment in complex environments.

G6PD maintains the VSMC synthetic phenotype and accelerates vascular neointimal hyperplasia by inhibiting the VDAC1-Bax-mediated mitochondrial apoptosis pathway.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) plays an important role in vascular smooth muscle cell (VSMC) phenotypic switching, which is an early pathogenic event in various vascular remodeling diseases (VRDs). However, the underlying mechanism is not fully understood. METHODS: An IP‒LC‒MS/MS assay was conducted to identify new binding partners of G6PD involved in the regulation of VSMC phenotypic switching under platelet-derived growth factor-BB (PDGF-BB) stimulation. Co-IP, GST pull-down, and immunofluorescence colocalization were employed to clarify the interaction between G6PD and voltage-dependent anion-selective channel protein 1 (VDAC1). The molecular mechanisms involved were elucidated by examining the interaction between VDAC1 and apoptosis-related biomarkers, as well as the oligomerization state of VDAC1. RESULTS: The G6PD level was significantly elevated and positively correlated with the synthetic characteristics of VSMCs induced by PDGF-BB. We identified VDAC1 as a novel G6PD-interacting molecule essential for apoptosis. Specifically, the G6PD-NTD region was found to predominantly contribute to this interaction. G6PD promotes VSMC survival and accelerates vascular neointimal hyperplasia by inhibiting VSMC apoptosis. Mechanistically, G6PD interacts with VDAC1 upon stimulation with PDGF-BB. By competing with Bax for VDAC1 binding, G6PD reduces VDAC1 oligomerization and counteracts VDAC1-Bax-mediated apoptosis, thereby accelerating neointimal hyperplasia. CONCLUSION: Our study showed that the G6PD-VDAC1-Bax axis is a vital switch in VSMC apoptosis and is essential for VSMC phenotypic switching and neointimal hyperplasia, providing mechanistic insight into early VRDs.

Accelerated Wound Healing by Electrospun Multifunctional Fibers with Self-Powered Performance.

Wound healing has been a persistent clinical challenge for a long time. Electrical stimulation is an effective therapy with the potential to accelerate wound healing. In this work, the self-powered electrospun nanofiber membranes (triples) were constructed as multifunctional wound dressings with electrical stimulation and biochemical capabilities. Triple was composed of a hydrolyzable inner layer with antiseptic and hemostatic chitosan, a hydrophilic core layer loaded with conductive AgNWs, and a hydrophobic outer layer fabricated by self-powered PVDF. Triple exhibited presentable wettability and acceptable moisture permeability. Electrical performance tests indicated that triple can transmit electrical signals formed by the piezoelectric effect to the wound. High antibacterial activities were observed for triple against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, with inhibition rates of 96.52, 98.63, and 97.26%, respectively. In vitro cell assays demonstrated that triple cells showed satisfactory proliferation and mobility. A whole blood clotting test showed that triple can enhance hemostasis. The innovative self-powered multifunctional fibers presented in this work offer a promising approach to addressing complications and expediting the promotion of chronic wound healing.

CD2AP is a potential prognostic biomarker of renal clear cell carcinoma.

BACKGROUND: CD2-associated protein (CD2AP) is a podocyte-associated gene and its reduced expression is associated with the development of proteinuria and glomerulosclerosis. However, few studies have focused on the correlation between the expression and prognosis of CD2AP in renal clear cell carcinoma (ccRCC). Therefore, we aimed to assess the regulation of CD2AP expression and prognostic value in ccRCC. METHODS: Multiple databases were employed to examine the expression of CD2AP in ccRCC. RT-qPCR, Western Blot and immunohistochemistry were used to validate CD2AP expression in different cell lines and tissue samples. Kaplan-Meier analysis and ROC curve analysis were performed on the predictive prognostic performance of CD2AP. COX regression was used to construct CD2AP-related prognostic models. The TIMER and TISIDB databases were used to analyze the correlation of tumor-infiltrating immune cells with gene expression, mutations, somatic copy number variation, and immune molecules. Mass spectrometry was used to detect methylation status of the promoter CpG site of CD2AP in multiple cells. RESULTS: We found that CD2AP expression was downregulated in ccRCC and its lower expression level was correlation with worse patient prognosis, higher tumor stage and grade and distant metastasis through analysis of databases, ccRCC cell lines and clinical tissue samples. Moreover, database and mass spectrometry techniques identified and validated cg12968598 hypermethylation as one of the key reasons for the downregulation of CD2AP expression. CD2AP expression was also associated with macrophage and neutrophil infiltration. CONCLUSIONS: Taken together, our results suggest that CD2AP can be used as a diagnostic and prognostic biomarker in ccRCC patients and that DNA hypermethylation plays an important role in reducing CD2AP expression.

Comparing the efficacy of a multi-dimensional breast cancer rehabilitation programme versus a home-based exercise programme during adjuvant cancer treatment.

BACKGROUND: Breast cancer is the most common female malignancy worldwide and a major cause of morbidity and mortality. Exercise during adjuvant treatment improves function and relieves symptoms in breast cancer survivors. However, it is unclear if an unsupervised exercise programme may be as effective as a supervised multimodal group. We investigated the feasibility and efficacy of a centre-based multidimensional rehabilitation (MDR) programme for breast cancer survivors undergoing adjuvant treatment and compared it to an unsupervised home-based exercise (HE) programme. METHODS: Participants were self-allocated to either MDR or HE group. MDR participants underwent 24 supervised exercise classes and 10 education classes over 12 weeks. HE participants were instructed on a home exercise regime. Outcome measures, including the 6-min walk test (6MWT) and Frenchay Activities Index (FAI), FACT-Cognitive Function scale, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, were conducted at baseline (W0), post-intervention (W12) and 6-months post-intervention (M6). Variance between time points and the 2 groups were analysed using a linear mixed model (unstructured covariance matrix) and adjusted with Bonferroni. RESULT: Twenty-five participants attended at least half of the MDR interventions, while 21 completed the HE interventions. The former showed significant improvement in 6MWT, from 406.88 m (W0) to 443.34 m (W12) to 452.81 m (M6), while the improvement in the HE group was not significant (407.67 m (W0) to 433.14 m (W12) to 430.96 m (M6)). Both groups showed a significant improvement in FAI, with earlier significant improvement noted at W12 in the MDR group (22.71 (W0) to 27.65 (W12) to 28.81 (M6)) compared to the HE group (23.16 (W0) to 26.47 (W12) to 29.85 (M6)). Dropout rate was 16% in the MDR group and 34% in HE group. Overall satisfaction with the MDR programme was high. CONCLUSION: Both MDR and HE programmes were feasible. MDR was superior in improving endurance and earlier return to instrumental activities for those who completed at least half of the sessions. Future studies could explore use of technology to improve adherence to exercise. TRIAL REGISTRATION: The study was registered with ClinicalTrial.gov on 01/04/2022 with the registration number NCT05306808.

ZIF-8@CsPbBr3 Nanocrystals Formed by Conversion of Pb to CsPbBr3 in Bimetallic MOFs for Enhanced Photocatalytic CO2 Reduction.

Perovskite nanocrystals are embedded into metal-organic frameworks (MOFs) to create composites with high light absorption coefficients, tunable electronic properties, high specific surface area, and metal atom tunability for enhanced photocatalytic carban dioxide (CO2 ) reduction. However, existing perovskite-MOF structures with a large particle size are achieved based on Pb source adsorption into the pores of MOFs, which can significantly break down the porous structure, thereby resulting in a decreased specific surface area and impacting CO2 adsorption. Herein, a novel perovskite-MOF structure based on the synthesis of bimetallic Pb-containing MOFs and post-processing to convert Pb to CsPbBr3 nanocrystals (NCs) is proposed. It is discovered that the additional Pb is not introduced by adsorption, but instead engages in coordination and generates Pb-N. The produced ZIF-8@CsPbBr3 NCs are ≈40 nm and have an ultra-high specific surface area of 1325.08 m2 g-1 , and excellent photovoltaic characteristics, which are beneficial for photocatalytic CO2 reduction. The electronic conversion rate of composites is 450 mol g-1 h-1 , which is more than three times that of pure perovskites. Additionally, the superior reduction capacity is sustained after undergoing four cycles. Density Functional Thoery (DFT) simulations are used to explore the 3D charge density at the ZIF-8@CsPbBr3 NCs interface to better understand the electrical structure.

The controllable and efficient synthesis of two-dimensional metal-organic framework nanosheets for heterogeneous catalysis.

Two-dimensional (2D) MOFs exhibit unique periodicity in surface structures and thus have attracted much interest in the fields of catalysis, energy, and sensors. However, the expanded production scale of 2D MOFs had remained a great challenge in most previous studies. Herein, a controllable and efficient crystallization method for synthesizing 2D MOF nanosheets using high-gravity reactive precipitation is proposed, significantly improving heterogeneous catalysis efficiency. The two-dimensional ZIF-L nanosheets prepared in a rotating packed bed (RPB) reactor show a smaller lateral and lamellar thickness and a higher BET surface area compared to ZIF-L nanosheets prepared in a conventional stirred tank reactor (STR), with a greatly shortened reaction time. Applying the ZIF-L-RPB nanosheets as a catalyst, the catalytic Knoevenagel condensation as a probe reaction displays a high conversion rate of benzaldehyde (99.3%) within 2 h at room temperature, greatly exceeding that displayed by ZIF-L-STR and other reported catalysts. Furthermore, ZIL-L-RPB nanosheets of only 0.2 wt% enhanced the catalytic activity for the glycolysis of poly(ethylene terephthalate) (PET) with a PET conversion and a monomer yield of 90% in a short period of 15 min at 195 °C and almost completely depolymerized PET with a monomer yield of 94% in 30 min, which was far above that achieved by ZIL-L-STR. These results indicate the promising prospects of a high-gravity reactive precipitation strategy with precise size control in an economical way to prepare high-activity 2D MOF nanosheets for a wide range of heterogeneous catalysis.

A Universal Approach for Controllable Synthesis of Homogeneously Alloyed PtM Nanoflowers toward Enhanced Methanol Oxidation.

Platinum (Pt)-based alloys have received considerable attention due to their compositional variability and unique electrochemical properties. However, homogeneous element distribution at the nanoscale, which is beneficial to various electrocatalytic reactions, is still a great challenge. Herein, a universal approach is proposed to synthesize homogeneously alloyed and size-tunable Pt-based nanoflowers utilizing high gravity technology. Owing to the significant intensification of micro-mixing and mass transfer in unique high gravity shearing surroundings, five typical binary/ternary Pt-based nanoflowers are instantaneously achieved at room temperature. As a proof-of-concept, as-synthesized Platinum-Silver nanoflowers (PtAg NFs) demonstrate excellent catalytic performance and anti-CO poisoning ability for anodic methanol oxidation reaction with high mass activity of 1830 mA mgPt -1, 3.5 and 3.2 times higher than those of conventional beaker products and commercial Pt/C, respectively. The experiment in combination with theory calculations suggest that the enhanced performance is due to additional electronic transmission and optimized d-band center of Pt caused by high alloying degree.

Mechanism of salvianolic acid B protecting H9C2 from OGD/R injury based on mitochondrial fission and fusion / 药学学报

This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.

Redox/Near-Infrared Dual-Responsive Hollow Mesoporous Organosilica Nanoparticles for Pesticide Smart Delivery.

Extremely inefficient utilization of pesticides has prompted a study of low-cost, sustainable, and smart application systems. Herein, as a promising pesticide nanocarrier, hollow mesoporous organosilica nanoparticles (HMONs) were first synthesized by using inexpensive CaCO3 nanoparticles as the hollow templates. A redox/near-infrared light dual-triggered pesticide release system was further achieved via loading avermectin (AVM) into the HMONs and coating a layer of polydopamine (PDA). The as-prepared AVM@HMONs@PDA displays a favorable pesticide load capability (24.8 wt %), outstanding photothermal performance, and high adhesion to leaves. In addition, with glutathione (GSH), the AVM cumulative release from AVM@HMONs@PDA was 3.5 times higher than that without GSH. Under ultraviolet light irradiation, the half-life of AVM@HMONs@PDA was prolonged by 17.0-fold compared to that of the AVM technical. At day 21 after treatment in the insecticidal activity, the median lethal concentrations (LC50) values displayed that the toxicity of AVM@HMONs@PDA for Panonychus citri (McGregor) was enhanced 4.0-fold compared with the commercial emulsifiable concentrate. In the field trial, at day 28 after spraying, AVM@HMONs@PDA was significantly more control effective than AVM-EC in controlling the P. citri (McGregor), even at a 50% reduced dosage. Moreover, HMONs@PDA was safe for crops. This research presents a novel preparation approach for HMONs, and it also offers a promising nanoplatform for the precise release of pesticides.

Innate Root Exudates Contributed to Contrasting Coping Strategies in Response to Ralstonia solanacearum in Resistant and Susceptible Tomato Cultivars.

Tomato cultivars with contrasting resistance to pathogens regulate root exudates differentially in response to Ralstonia solanacearum attacks. However, strategies using innate root exudates against infection remain unknown. This study analyzed the innate root exudates of two tomato cultivars and their functions in regulating R. solanacearum infection. The innate root exudates differed between the two cultivars. Astaxanthin released from resistant plants inhibited colonization by R. solanacearum but promoted motility, while neferine released from susceptible plants suppressed motility and colonization. The secretion of astaxanthin in resistant tomatoes promoted the growth of biocontrol fungi in soil and reduced the abundance of pathogenic fungi. Neferine secreted by the susceptible cultivar inhibited the relative abundance of the bacterial-biocontrol-related Bacillus genus, indirectly reducing the soil's immune capacity. This study revealed contrasting strategies using root exudates in resistant and susceptible tomato cultivars to cope with R. solanacearum infection, providing a basis for breeding disease-resistant cultivars.

Efficient Construction of pH-Stimuli-Responsive Colloidosomes with High Encapsulation Efficiency.

Intelligent responsive colloidosomes have attracted increasing attention for their potential to enhance the efficacy and decrease the side effects of drugs in biomedical applications. However, a low encapsulation efficiency and complicated preparation method greatly limit their development. Herein, we report an efficient approach for the construction of pH-stimuli-responsive colloidosomes with high encapsulation efficiency by a high-gravity technology. The conditions under which latex particles with different methacrylic acid contents can successfully self-assemble into colloidosomes are explored. During the preparation process, emulsions emulsified for only 10 min at 2500 rpm in a unique high-gravity shearing surroundings are clarified owing to the greatly enhanced micromixing, while the emulsions emulsified for 30 min by a traditional high-speed shear machine at 4000 rpm are still yellow-white. More importantly, regular spherical colloidosomes encapsulating an anticancer drug doxorubicin not only achieve a small mean diameter of 2.82 µm but also realize a high encapsulation efficiency of 76.5%. The release performance of doxorubicin has an obvious pH-stimuli-responsive regularity and follows the first-order model of sustained release. The construction of intelligent responsive colloidosomes as drug carriers provides a route for controlled drug release and biomedical applications.

Sarcopenia in liver cirrhosis: perspectives from epigenetics and microbiota.

Sarcopenia is characterized by the loss of muscle mass and function. It is well known that sarcopenia is often associated with aging, while in recent years, sarcopenia comorbid with chronic diseases such as cirrhosis has attracted widespread attention, whose underlying molecular mechanisms remain unclear. Since cirrhosis and sarcopenia are assumed to be closely interrelated in terms of pathogenesis, this review innovatively discussed the role of epigenetic modifications and microecological dysregulation in sarcopenia in the context of liver cirrhosis. Here we illustrated the relationship between sarcopenia and cirrhosis in the aspect of epigenetics, dysbiosis, and the crosstalk between gene modifications and intestinal microecology. Furthermore, the alterations in cirrhosis patients with sarcopenia, such as inflammatory response and oxidative stress, are found to present synergistic effects in the pathways of epigenetics and dysbiosis leading to sarcopenia. This review proposes that microbiome-based therapies are promising to break the vicious cycle between epigenetic modification and dysbiosis, providing strong support for the use of intestinal microecological interventions to prevent sarcopenia in cirrhotic patients.

Study on signal transmission mechanism of arbuscular mycorrhizal hyphal network against root rot of Salvia miltiorrhiza.

To explore the signal transmission mechanism of the arbuscular mycorrhizal network against root rot of Salvia miltiorrhiza. In this experiment, the arbuscular mycorrhizal hyphal network was established among Salvia miltiorrhiza plants, and a two plant three-compartment culture model was established. The root of the donor Salvia miltiorrhiza was inoculated with the pathogenic fungi Fusarium solani. The changes of hormone signals such as jasmonic acid and salicylic acid and the expression of related defense genes in the recipient Salvia miltiorrhiza plants in different periods were measured, to study the underground disease resistance signal transmission mechanism among medicinal plants. Salvia miltiorrhiza can transmit the signal of resistance to root rot through the jasmonic acid pathway; When plants suffer from disease stress, the content of JA increases significantly, and the increase of JA content will inhibit the content of SA in plants; The gene expression of PR-10 gene in the roots of Salvia miltiorrhiza with arbuscular mycorrhizal network infected by pathogenic fungi was 17.56 times higher than that inoculated only with pathogenic fungi; Changes in hormone content will also cause changes in the expression of related defense genes, such as SnRK2 is inhibited by ABA in the signal transduction pathway, while JA and ABA show antagonistic changes after inoculation of pathogenic fungi in Salvia miltiorrhiza, so JA may positively regulate the expression of SnRK2 gene. Plants can transmit signals through AM hyphal network after being stressed by the pathogen Fusarium solani. In the arbuscular mycorrhizal hyphal network, JA has important significance for the signal transmission of resistance to root rot and disease resistance of Salvia miltiorrhiza, which can make Salvia miltiorrhiza ready for stress resistance and improve the stress resistance of Salvia miltiorrhiza. This experiment is of great significance to further analyze the signal transmission mechanism of the arbuscular mycorrhizal hyphal network.

Degradable PDA@PNIPAM-TA Nanocomposites for Temperature- and NIR light-Controlled Pesticide Release.

Controlled pesticide delivery systems offer many distinctive advantages over conventional pesticide formulations. In this work, degradable poly(N-isopropylacrylamide) (PNIPAM)-tannic acid (TA) microgels and multifunctional PDA@PNIPAM-TA nanocomposites were prepared in a high-gravity rotating packed bed reactor (RPB) for smart pesticide delivery and release. The as-prepared microgels and nanocomposites showed reversible temperature-dependent swelling/deswelling behavior and irreversible pH-induced degradation. A dynamic contact angle test suggested that the introduction of TA and PDA into the PNIPAM matrix could enhance foliar adhesion and deposition efficiency. The nanocomposites were further used for the encapsulation and delivery of imidacloprid (IMI) to protect it from rapid photolysis and improve its pest-control efficiency. Their thermoresponsive behavior as well as pesticide loading capacity could be tuned by tailoring the PNIPAM-TA shell thickness, which could be varied by the NIPAM amount. The release rate of IMI from the core/shell nanocomposites was positively correlated with environmental temperature and near-infrared (NIR) light, which was adaptive to the positive temperature-dependent toxicity correlation of IMI and the increasing trend of pests under high temperature. The cumulative release of IMI was 23.5% at 25 °C, while it was 81.2% at 40 °C after 24 h of incubation, and the release rate was greatly enhanced under NIR irradiation. The results indicated that the facile control of pesticide release could be realized by regulating environmental conditions. This work also provides an idea for using high-gravity technology to conveniently construct a smart, effective, and environmentally friendly pesticide delivery system for sustainable crop protection.

Congenital thrombophilia in East-Asian venous thromboembolism population: a systematic review and meta-analysis.

Background: Various inherited traits contribute to the overall risk of venous thromboembolism (VTE). In addition, the epidemiology of thrombophilia in the East-Asian VTE population remains unclear; thus, we aimed to assess the proportion of hereditary thrombophilia via a meta-analysis. Methods: Publications from PubMed, EMBASE, web of science, and Cochrane before December 30, 2022, were searched. Studies from Japan, Korea, China, Hong Kong, Taiwan, Singapore, Thailand, Vietnam, Myanmar, and Cambodia were included. Congenital thrombophilia was described as diseases including protein C (PC) deficiency, protein S (PS) deficiency, antithrombin (AT) deficiency, factor (F)V Leiden (FVL), and prothrombin G20210A mutations. Studies were selected by 2 reviewers for methodological quality analysis. A random-effects model was used for the meta-analysis, assuming that estimated effects in the different studies are not identical. Results: Forty-four studies involving 6453 patients from 7 counties/regions were included in the meta-analysis. The prevalence of PC, PS, and AT deficiencies were 7.1%, 8.3%, and 3.8%, respectively. Among 2924 patients from 22 studies, 5 patients were carriers of FVL mutation. Among 2196 patients from 10 studies, 2 patients were carriers of prothrombin G20210A mutation in a Thailand study. Conclusion: The prevalence of PC, PS, and AT deficiencies was relatively high, while a much lower prevalence of FVL and prothrombin G20210A mutations were identified in East-Asian patients with VTE. Our data stress the relative higher prevalence of PC, PS, and AT deficiencies for thrombophilia in the East-Asian VTE population.

Lytic efficiency of immunosuppressive drug-resistant armoured T cells against circulating HBV-related HCC in whole blood.

Recurrence of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) after liver transplant (LT) is mediated by circulating tumour cells (CTCs) and exacerbated by the immunosuppressants required to prevent graft rejection. To circumvent the effects of immunosuppressants, we developed immunosuppressive drug-resistant armoured HBV-specific T-cell receptor-redirected T cells (IDRA HBV-TCR). However, their ability to eliminate HBV-HCC circulating in the whole blood has never been tested, and whether their lytic efficacy is compatible with the number of adoptively transferred T cells in vivo has never been measured. Hence, we developed a microscopy-based assay to quantify CTCs in whole blood. The assay was then used to quantify the efficacy of IDRA HBV-TCRs to lyse free-floating HBV-HCC cells in the presence of Tacrolimus and Mycophenolate Mofetil (MMF). We demonstrated that a panel of antibodies (AFP, GPC3, Vimentin, pan-Cytokeratin, and CD45) specific for HCC tumour antigens and immune cells can effectively differentiate HCC-CTCs in whole blood. Through dose-titration experiments, we observed that in the presence of immunosuppressive drugs, a minimum of 20 000 IDRA HBV-TCR T cells/ml of whole blood is necessary to lyse ~63.5% of free-floating HBV-HCC cells within 16 hours. In conclusion, IDRA HBV-TCR T cells can lyse free-floating HBV-HCC cells in whole blood in the presence of Tacrolimus and MMF. The quantity of IDRA-HBV TCR T cells required can be achieved by the adoptive transfer of 5 × 106 IDRA-HBV TCR-T cells/kg, supporting the utilisation of IDRA HBV-TCR T cells to eliminate CTCs as prophylaxis against recurrence after LT.

Smartphone ownership, digital literacy, and the mediating role of social connectedness and loneliness in improving the wellbeing of community-dwelling older adults of low socio-economic status in Singapore.

INTRODUCTION: During the COVID-19 pandemic, safe-distancing measures resulted in many community-dwelling older adults being socially isolated and lonely, with its attending negative impact on wellbeing and quality of life. While digital technology may have mitigated this, older adults of low socioeconomic status (SES) are more likely to be digitally excluded and hence susceptible to the adverse effects of social isolation and loneliness. This study aims to understand the factors that affect digital literacy, smartphone ownership, and willingness to participate in a digital literacy program (DLP), and to test the hypothesized relations between digital literacy, social connectedness, loneliness, wellbeing, and quality of life amongst community dwelling older adults of low SES. MATERIALS AND METHODS: A questionnaire assessing digital literacy, social connectedness, wellbeing and quality of life was administered. Socio-demographic variables, pre-existing internet-enabled, and willingness to participate in a home-based DLP was also collected. Logistic regression was used to identify demographic factors associated with digital literacy, smartphone ownership, and willingness to enroll in a DLP. Serial mediation analysis was also performed using a structural equation model framework. RESULTS: A total of 302 participants were recruited. Female gender, older age, lower education levels were associated with lower digital literacy. Those who owned a smartphone tended to be younger and better educated. Older adults who were better educated, of Chinese descent (the ethnic majority in Singapore), and who had lower digital literacy, were most willing to enroll in the digital literacy education program. Social-use digital literacy had a positive indirect effect on well-being ([Formula: see text]) and Quality of life ([Formula: see text]), mediated by social connectedness and loneliness. In contrast, instrumental-use digital literacy had a negative indirect effect on well-being ([Formula: see text]) and Quality of life ([Formula: see text]), mediated by social connectedness and loneliness. DISCUSSION: The results suggest there are demographic barriers to participation in DLPs and highlight the benefit of focusing on enhancing social-use digital literacy. Further study is needed to evaluate how well specific interventions to improve social-use digital literacy help to reduce social isolation and loneliness, and ultimately improve wellbeing and quality of life.

Greatly Intensified Guest Exchange Strategy for Highly-Efficient Activation of Metal-Organic Frameworks.

The preservation and accessibility of pores are prerequisites to the application of metal-organic frameworks (MOFs). Activation is a key step to eliciting rich features of pores, but it needs a repeated solvent-exchange process which is tedious and time/cost-consuming. Herein, a facile strategy for highly-efficient activation of MOFs utilizing rotating packed bed is proposed. With the tremendous enhancement of molecular mixing and mass transfer in high-gravity and strong-shearing surrounding, nine representative MOFs are completely activated within 2 h without structural change. Compared with conventional process, this activation displays surprising efficiency by accelerating the diffusion of solvents and redissolution of residual reactants in the pores. The complete activation time can be significantly shortened by over 90%. As a proof-of-concept, the methane storage of as-activated UiO-66 is five times that of as-synthesized UiO-66. This strategy provides a potential platform with industrial worth for the activation of MOF materials with ultra-high efficiency and versatility.

Effects of long-term exposure to high altitude on brain structure in healthy people: an MRI-based systematic review and meta-analysis.

Purpose: To conduct a systematic review and meta-analysis of observational studies of brain MRI, this paper assesses the effects of long-term exposure to high-altitude on brain structures in healthy people. Methods: Observational studies related to high-altitude, brain and MRI were systematically searched based on data retrieved from PubMed, Embase and Cochrane Library. The timescale for collecting literature was from the establishment of the databases to 2023. NoteExpress 3.2 was used to manage the literature. Two investigators performed literature screening and data extraction based on inclusion criteria, exclusion criteria, and literature quality. The quality of the literature was assessed using the NOS Scale. Finally, meta-analysis of included studies was performed using Reviewer Manager 5.3. Results: Initially, 3,626 articles were retrieved. After screening, 16 articles (n = 756 participants) were included in the systematic review, and meta-analysis was performed on 6 articles (n = 350 participants). The overall quality of the included articles was at medium level, with a mean NOS score of 5.62. The results of meta-analysis showed that the differences between the HA group and LA group were not statistically significant, in total GM volume (MD: -0.60, 95% CI: -16.78 to 15.58, P = 0.94), WM volume (MD: 3.05, 95% CI: -15.72 to 21.81, P = 0.75) and CSF volume (MD: 5.00, 95% CI: -11.10 to 21.09, P = 0.54).The differences between HA and LA in FA values of frontotemporal lobes were not statistically significant: right frontal lobe (MD: -0.02, 95% CI: -0.07 to 0.03, P = 0.38), left frontal lobe (MD: 0.01, 95% CI: -0.02 to 0.04, P = 0.65), right temporal lobe (MD: -0.00, 95% CI: -0.03 to 0.02, P = 0.78) and left temporal lobe (MD: -0.01, 95% CI: -0.04 to 0.02, P = 0.62). However, there were significant differences in GM volume, GM density and FA values in local brain regions between HA group and LA group. Conclusion: Compared with LA area, there were no significant differences in total GM, WM and CSF volumes in healthy people living at high-altitude area for long-term, while there were significant differences in GM volume and FA values in local brain regions. Long-term exposure to high-altitude area caused the adaptive structural changes in local brain regions. Since heterogeneity existed between the studies, further studies are needed to uncover the effects of high-altitude on brain of healthy people. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023403491.