An Inhalable Nanoshield for Effective Prevention of Influenza Virus Infections.

Influenza virus (IV) infection currently poses a serious and continuing threat to the global public health. Developing effective prevention strategies is important to defend against infection and spread of IV. Here, we developed a triple-protective nanoshield against IV infection in the lungs, formed by self-assembling DSPE-PEG amphiphilic polymers encapsulating the flu-preventive antiviral drug Arbidol internally. The preventive effect of the nanoshield against virus infection includes increasing the viscosity in the surrounding environment to physically defend against viral entry, forming a hydrated layer to block the interaction between viruses and cells, and inhibiting virus replication. Our finding suggested that a single inhalation of the nanoshield provides effective protection against IV infection for at least 8 h. Thus, this nanoshield may be a potential pandemic protection agent against IV, especially in viral environments, where no prophylactic or therapeutic measures are available.

Underlying mechanisms of change in the effects of cognitive behavior therapy on posttraumatic stress disorders among Chinese children: Results from a randomized controlled trial.

BACKGROUND: Evidence for the effectiveness of group-based trauma-focused cognitive behavior therapy (TF-CBT) has existed, but little is known about how group-based TF-CBT works in the treatment of children with PTSD. The purpose of the present study is to explore the mediators for the reduction of PTSD severity in group-based TF-CBT. METHOD: We analyzed data from a randomized controlled trial conducted in China. In this trial, 234 children with PTSD were randomly assigned to the TF-CBT group or the treatment as usual (TAU) group. The primary outcome (reduction in severity of PTSD symptoms) and possible mediators (trauma memory quality, emotion regulation strategies, and resilience) were assessed at baseline and posttreatment. The mediation analysis was performed to investigate the indirect effects of possible mediators on treatment outcomes. RESULTS: The mediation model revealed that changes in trauma memory quality, maladaptive emotion regulation strategies, and resilience mediated the relationship between the group (TF-CBT vs. TAU) and PTSD at post-treatment. Adaptive emotion regulation strategies were not a key mechanism underlying PTSD reduction in group-based TF-CBT. CONCLUSION: Group-based TF-CBT might affect PTSD by reducing risk factors, like trauma memory quality and maladaptive emotion strategies. Group-based TF-CBT also might affect PTSD by increasing protective factors, like resilience. Thus, monitoring these mediators throughout treatment might be an important factor in optimizing treatment outcomes.

Etelcalcetide ameliorates bone loss in chronic kidney disease-mineral and bone disorder by activation of IRF7 and necroptosis pathways.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a multifaceted clinical syndrome characterized by mineral imbalances, abnormalities in bone metabolism, chronic inflammation and vascular calcification. Etelcalcetide, a second-generation intravenous calcimimetic agent, has been approved for treating high-turnover renal osteodystrophy, effectively targeting the pathophysiological mechanisms underlying this condition. We investigate the impacts of etelcalcetide on osteoclast (OC) differentiation and functionality in CKD-MBD via three critical mechanisms: inflammation initiated by interferon regulatory factor 7 (IRF7), receptor-interacting protein (RIP)-mediated necroptosis and apoptosis-induced cell death. The low-dose (CKD + L) or high-dose (CKD + H) of etelcalcetide groups significantly improved biochemical markers compared to the CKD control mice. Additionally, etelcalcetide-treated CKD mice significantly improved cortical and trabecular bone parameters. In an in vitro study, etelcalcetide was observed to bolster the IRF7-mediated IFNß response in OC differentiation. Furthermore, it stimulated RIP-mediated necroptosis via RIP and MLKL activation, inhibiting bone resorption. Moreover, the drug increased levels of caspases 3 and 9, inducing cell death in OCs. These findings suggest that etelcalcetide regulates bone metabolism and reduces skeletal issues in CKD-MBD. Etelcalcetide likely enhances bone parameters in CKD-MBD mice by regulating IRF7 pathways and inhibiting OC differentiation. It also improves bone health and promotes RIP-mediated necroptosis and apoptosis pathways within OCs.

High-efficiency and thermally stable FACsPbI3 perovskite photovoltaics.

α-FA1-xCsxPbI3 is a promising absorber material for efficient and stable perovskite solar cells (PSCs)1,2. However, the most efficient α-FA1-xCsxPbI3 PSCs require the inclusion of methylammonium chloride (MACl) additive3,4, which generates volatile organic residues (i.e., MA) that limit device stability at elevated temperatures5. To date, the highest certified power-conversion efficiency (PCE) of α-FA1-xCsxPbI3 PSCs without MACl was only ~24% (ref.6,7), and has yet to exhibit any stability advantages. Here, we identify interfacial contact loss caused by the Cs+ accumulation for the conventional α-FA1-xCsxPbI3 PSCs, which deteriorates the device performance and stability. Through in-situ GIWAXS analysis and DFT calculations, we demonstrate an intermediate phase-assisted crystallization pathway enabled by acetate surface coordination to fabricate high-quality α-FA1-xCsxPbI3 film, without using MA-additive. We herein report a certified stabilized power output (SPO) efficiency of 25.94% and a reverse-scanning PCE of 26.64% for α-FA1-xCsxPbI3 PSCs, exhibiting negligible contact losses and enhanced operational stability. The devices retain >95% of their initial PCEs after over 2,000 hours operating at maximum power point under 1 sun, 85 °C, and 60% relative humidity (ISOS-L-3).

Physics-Informed Active Learning for Accelerating Quantum Chemical Simulations.

Quantum chemical simulations can be greatly accelerated by constructing machine learning potentials, which is often done using active learning (AL). The usefulness of the constructed potentials is often limited by the high effort required and their insufficient robustness in the simulations. Here, we introduce the end-to-end AL for constructing robust data-efficient potentials with affordable investment of time and resources and minimum human interference. Our AL protocol is based on the physics-informed sampling of training points, automatic selection of initial data, uncertainty quantification, and convergence monitoring. The versatility of this protocol is shown in our implementation of quasi-classical molecular dynamics for simulating vibrational spectra, conformer search of a key biochemical molecule, and time-resolved mechanism of the Diels-Alder reaction. These investigations took us days instead of weeks of pure quantum chemical calculations on a high-performance computing cluster.

Transcriptome analysis of rats with chronic unpredictable mild stress treated with electroacupuncture.

BACKGROUND: Depression remains one of the most prevalent psychiatric disorders, with many patients not responding adequately to available treatments. Electroacupuncture (EA), a nonpharmacologic therapy, holds great promise for alleviating depressive symptoms. In this study, RNA sequencing (RNA-Seq) was used to identify genome-wide alterations in the hippocampus of rats after chronic unpredictable mild stress (CUMS) and EA treatments to further elucidate the mechanism by which EA ameliorates depression to provide a basis for the clinical application of EA in stress-related diseases. METHODS: The sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST) were used to investigate the ability of EA at Baihui (GV20) and Taichong acupoints (LR3) to improve depression-like behavior in rats subjected to CUMS. Subsequently, RNA-Seq analysis revealed transcriptomic profiles of the hippocampus of rats subjected to CUMS in which EA ameliorated depressive behavior. Finally, the expression profiles of major differentially expressed genes were tested by real-time quantitative polymerase chain reaction (qRT-PCR) to determine the accuracy of the RNA-Seq results. RESULTS: Rats subjected to CUMS exhibited depressive-like behaviors, such as decreased sucrose consumption in the SPT (p < .001), decreased time in the central area of the OFT (p < .001), and increased immobility in the FST (p < .01). Importantly, rats subjected to CUMS and treated with EA showed increased sucrose consumption (p < .001), increased time spent in the central area of the OFT (p < .001) and decreased immobility in the FST (p < .01). Sixty-three genes that were differentially expressed following CUMS were altered by EA; most of these were associated with immune pathways. Compared with those in the control group, the expression levels of Colla2 (p < .001), Col3a1 (p < .001), Psmb9 (p < .01), and Tap1 (p < .01) in the hippocampus of rats subjected to CUMS were lower. The changes in the expression of these genes were reversed by EA treatment. CONCLUSION: EA at GV20 and LR3 attenuated CUMS-induced depression-like behaviors by regulating the expression of specific genes such as Colla2, Col3a1, Psmb9, and Tap1.

Total Biosynthesis of Circular Bacteriocins by Merging the Genetic Engineering and Enzymatic Catalysis.

Circular bacteriocins are known for their structural stability and effective antimicrobial properties, positioning them as potential natural food preservatives. However, their widespread application is impeded by restricted availability. This research developed a total biosynthesis platform for circular bacteriocins, with a focus on AS-48 by involving recombinant production of the linear precursor in Escherichia coli, followed by enzymatic cyclization of the precursor into cyclic AS-48 using the ligase butelase-1 in vitro. An important discovery is that, aside from fusion tags, the C-terminal motif LE and LEKKK also could affect the expression yield of the precursor. This biosynthesis platform is both versatile and high-yielding, achieving yields of 10-20 mg/L of AS-48. Importantly, the biosynthetic AS-48 exhibited a secondary structure and antimicrobial activities comparable to those of the native molecules. As such, this work proposes an effective synthetic approach for circular bacteriocins, facilitating their advancement and application in the food industry.

High-Resolution Magnetic Resonance Angiography of Tumor Vasculatures with an Interlocking Contrast Agent.

The comprehensive evaluation of tumor vasculature that is crucial for the development, expansion, and spread of cancer still remains a great challenge, especially the three-dimensional (3D) evaluation of vasculatures. In this study, we proposed a magnetic resonance (MR) angiography strategy with interlocking stratagem of zwitterionic Gd-chelate contrast agents (PAA-Gd) for continuous monitoring of tumor angiogenesis progression in 3D. Owing to the zwitterionic structure and nanoscale molecular diameter, the longitudinal molar relaxivity (r1) of PAA-Gd was 2.5 times higher than that of individual Gd-chelates on a 7.0 T MRI scanner, resulting in the higher-resolution visualization of tumor vasculatures. More importantly, PAA-Gd has the appropriate blood half-life (69.2 min), emphasizing the extended imaging window compared to the individual Gd-chelates. On this basis, by using PAA-Gd as the contrast agent, the high-resolution, 3D depiction of the spatiotemporal distribution of microvasculature in solid tumors formed by different cell lines over various inoculation times has been obtained. This method offers an effective approach for early tumor diagnosis, development assessment, and prognosis evaluation.

Macular Structure Characteristics in Unilateral Idiopathic Full-Thickness Macular Hole and the Healthy Fellow Eyes.

INTRODUCTION: This study aimed to investigate the macular structure and foveal pit characteristics in the unilateral full-thickness macular hole (FTMH) patients and healthy fellow eyes. METHODS: Our retrospective investigation included patients with unilateral FTMH as the study group, and age- and sex-matched individuals without vitreomacular diseases as the control group, all from one medical center. FTMHs were categorized into those with epiretinal proliferation, those without epiretinal proliferation, or those lacking vitreomacular separation. Macular parameters including foveal base width (FBW), central foveolar thickness (CFT), central subfield thickness (CST), central subfield volume, and retinal artery trajectory (RAT) were measured via optical coherence tomography and fundus photography. Comparisons of these parameters were made among lesioned eyes, contralateral healthy eyes and normal controls, as well as among different subgroups. RESULTS: Sixty-eight unilateral FTMH patients (39 women and 29 men) and 68 normal controls were enrolled. The fellow eyes of unilateral FTMH showed larger FBWs (446.8 ± 98.2 µm) than controls (338.4 ± 80.6 µm, p < 0.001). The lesioned and fellow eyes of unilateral FTMH had smaller RAT values (0.19 ± 0.06 and 0.14 ± 0.04) than controls (0.37 ± 0.14, p < 0.001), indicating wider RAT in both groups. No significant macular structure parameter differences were observed among different FTMH subgroups. Females exhibited larger FBW, thinner CFT and CST, and wider RAT than the age-matched males (p < 0.05). CONCLUSIONS: Patients with unilateral FTMH had a wider RAT in both the lesioned and healthy eyes and a wider FBW in their healthy fellow eyes than in controls. Such macular structure characteristics may be prone to macular hole formation.

Rational design of a two-dimensional high-temperature ferromagnet from HCP cobalt.

Cobalt has the highest Curie temperature (Tc) among the elemental ferromagnetic metals and has a hexagonal close-packed (HCP) structure at room temperature. In this study, HCP Co was thinned to the thickness of several (n) unit cells along the c-axis and then passivated by halogen atoms, thus being named Co2nX2 (X = F, Cl, Br and I). For Co2X2 and Co3X2, all of them are not only kinetically but also thermodynamically stable from the viewpoint of the phonon spectra and molecular dynamics. Similar to HCP Co, two-dimensional (2D) Co2F2, Co2Cl2 and Co3X2 (X = Cl, Br and I) are still ferromagnetic metals within the Stoner model but Co2X2 (X = Br and I) is a ferromagnetic half-metal with the coexistence of the metallic behavior for one spin and the insulating behavior for the other spin. Taking into account the spin-orbital coupling (SOC), the easy-magnetization axis is within the plane where the magnetization is isotropic, making it look like a 2D XY magnet. Applying a critical biaxial strain could lead to an easy-magnetization axis changing from the in-plane to the out-of-plane direction. Finally, we use classical Monte Carlo simulations to estimate the Curie temperature (Tc) which is as high as 957 and 510 K for Co2F2 and Co2Cl2, respectively, because of the strong direct exchange interaction. Different from being obtained by mechanical or liquid exfoliation from van der Waals layered structures, our study opens up new possibilities to search for novel 2D ferromagnets from the elemental ferromagnets and provides opportunities for realizing realistic ultra-thin spintronic devices.

Revealing Different Pathways for Influenza A Virus To Reach Microtubules after Endocytosis by Quantum Dot-Based Single-Virus Tracking.

Actin- and microtubule (MT)-based transport systems are essential for intracellular transport. During influenza A virus (IAV) infection, MTs provide long tracks for virus trafficking toward the nucleus. However, the role of the actin cytoskeleton in IAV entry and especially the transit process is still ambiguous. Here, by using quantum dot-based single-virus tracking, it was revealed that the actin cytoskeleton was crucial for the virus entry via clathrin-mediated endocytosis (CME). After entry via CME, the virus reached MTs through three different pathways: the virus (1) was driven by myosin VI to move along actin filaments to reach MTs (AF); (2) was propelled by actin tails assembled by an Arp2/3-dependent mechanism to reach MTs (AT); and (3) directly reached MTs without experiencing actin-related movement (NA). Therefore, the NA pathway was the main one and the fastest for the virus to reach MTs. The AT pathway was activated only when plenty of viruses entered the cell. The viruses transported by the AF and AT pathways shared similar moving velocities, durations, and displacements. This study comprehensively visualized the role of the actin cytoskeleton in IAV entry and transport, revealing different pathways for IAV to reach MTs after entry. The results are of great significance for globally understanding IAV infection and the cellular endocytic transport pathway.

MEIKIN expression and its C-terminal phosphorylation by PLK1 is closely related the metaphase-anaphase transition by affecting cyclin B1 and Securin stabilization in meiotic oocyte.

Oocyte meiotic maturation failure and chromosome abnormality is one of the main causes of infertility, abortion, and diseases. The mono-orientation of sister chromatids during the first meiosis is important for ensuring accurate chromosome segregation in oocytes. MEIKIN is a germ cell-specific protein that can regulate the mono-orientation of sister chromatids and the protection of the centromeric cohesin complex during meiosis I. Here we found that MEIKIN is a maternal protein that was highly expressed in mouse oocytes before the metaphase I (MI) stage, but became degraded by the MII stage and dramatically reduced after fertilization. Strikingly, MEIKIN underwent phosphorylation modification after germinal vesicle breakdown (GVBD), indicating its possible function in subsequent cellular event regulation. We further showed that MEIKIN phosphorylation was mediated by PLK1 at its carboxyl terminal region and its C-terminus was its key functional domain. To clarify the biological significance of meikin degradation during later stages of oocyte maturation, exogenous expression of MEIKIN was employed, which showed that suppression of MEIKIN degradation resulted in chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest through a spindle assembly checkpoint (SAC)-independent mechanism. Exogenous expression of MEIKIN also inhibited metaphase II (MII) exit and early embryo development. These results indicate that proper MEIKIN expression level and its C-terminal phosphorylation by PLK1 are critical for regulating the metaphase-anaphase transition in meiotic oocyte. The findings of this study are important for understanding the regulation of chromosome segregation and the prevention meiotic abnormality.

The short- and mid-term efficacy and safety of elagolix in the management of pain associated with endometriosis: A systematic review and meta-analysis.

BACKGROUND: Elagolix, an approved non-peptide GnRH antagonist, shows promise in relieving endometriosis-related pain, but its short- and mid-term efficacy and potential side effects are still under investigation. OBJECTIVE: The aim is to provide data for therapeutic applications by methodically evaluating elagolix's safety and effectiveness in treating endometriosis-related pain. METHODS: Databases such as PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and others were thoroughly searched. The search time was from the establishment date to September 2023. The study included randomized controlled trials (RCTs) that compared the efficacy of elagolix versus placebo in treating endometriosis-associated pain. After data extraction and literature scanning, quality assessment was carried out using Quality evaluation was carried out using the bias risk assessment tool suggested by the Cochrane Reviewers' Handbook 5.1.0 after literature screening and data extraction. Stata 15.0 was used to do the meta-analysis. RESULTS: In total, five RCTs involving 2056 patients were included in the analysis. The meta-analysis demonstrated a significant superiority of elagolix over placebo in the management of endometriosis-related pain, specifically in endometriosis pain [WMD=-0.77, 95% CI (-1.00, -0.53), P<0.001], as well as in non-menstrual pelvic pain, daily assessment of dysmenorrhea (DYS), and dyspareunia (DYSP), all of which are associated with endometriosis. Regarding safety, no discernible variation was observed in the incidence of serious adverse responses between the elagolix and placebo groups [RR=0.90, 95% CI (0.58, 1.40), P=0.643]. Conversely, the elagolix group exhibited a significantly higher incidence rate of general adverse responses [RR = 1.34, 95% CI (1.18, 1.52), P<0.001] compared to the control group. CONCLUSIONS: The efficacy of elagolix in reducing pain in premenopausal women with endometriosis has been demonstrated over the short- to mid-term. However, careful monitoring for potential adverse effects is essential throughout the treatment duration.

Association of redundant foreskin with sexual dysfunction: a cross-sectional study from 5700 participants.

A previous study showed that the length of the foreskin plays a role in the risk of sexually transmitted infections and chronic prostatitis, which can lead to poor quality of sexual life. Here, the association between foreskin length and sexual dysfunction was evaluated. A total of 5700 participants were recruited from the andrology clinic at The First Affiliated Hospital of University of Science and Technology of China (Hefei, China). Clinical characteristics, including foreskin length, were collected, and sexual function was assessed by the International Index of Erectile Function-5 (IIEF-5) and Premature Ejaculation Diagnostic Tool (PEDT) questionnaires. Men with sexual dysfunction were more likely to have redundant foreskin than men without sexual dysfunction. Among the 2721 erectile dysfunction (ED) patients and 1064 premature ejaculation (PE) patients, 301 (11.1%) ED patients and 135 (12.7%) PE patients had redundant foreskin, respectively. Men in the PE group were more likely to have redundant foreskin than men in the non-PE group (P = 0.004). Logistic regression analyses revealed that the presence of redundant foreskin was associated with increased odds of moderate/severe ED (adjusted odds ratio [aOR] = 1.31, adjusted P = 0.04), moderate PE (aOR = 1.38, adjusted P = 0.02), and probable PE (aOR = 1.37, adjusted P = 0.03) after adjusting for confounding variables. Our study revealed a positive correlation between the presence of redundant foreskin and the risk of sexual dysfunction, especially in PE patients. Assessment of the length of the foreskin during routine clinical diagnosis may provide information for patients with sexual dysfunction.

Intermittent protein restriction before but not after the onset of diabetic kidney disease attenuates disease progression in mice.

Background: High dietary protein intake exacerbates proteinuria in individuals with diabetic kidney disease (DKD). However, studies on the impacts of low protein diet (LPD) on DKD have yielded conflicting results. Furthermore, patient compliance to continuous protein restriction is challenging. Objective: The current study aims to investigate the effects of intermittent protein restriction (IPR) on disease progression of DKD. Methods: Diabetic KK-Ay mice were used in this study. For the IPR treatment, three consecutive days of LPD were followed by four consecutive days of normal protein diet (NPD) within each week. For early intervention, mice received IPR before DKD onset. For late intervention, mice received IPR after DKD onset. In both experiments, age-matched mice fed continuous NPD served as the control group. Kidney morphology, structure and function of mice in different groups were examined. Results: Intermittent protein restriction before DKD onset ameliorated pathological changes in kidney, including nephromegaly, glomerular hyperfiltration, tubular injuries and proteinuria, without improving glycemic control. Meanwhile, IPR initiated after DKD onset showed no renoprotective effects despite improved glucose homeostasis. Conclusion: Intermittent protein restriction before rather than after DKD onset protects kidneys, and the impacts of IPR on the kidneys are independent of glycemic control. IPR shows promise as an effective strategy for managing DKD and improving patient compliance.

Prodrug-inspired adenosine triphosphate-activatable celastrol-Fe(III) chelate for cancer therapy.

Celastrol (CEL), an active compound isolated from the root of Tripterygium wilfordii, exhibits broad anticancer activities. However, its poor stability, narrow therapeutic window and numerous adverse effects limit its applications in vivo. In this study, an adenosine triphosphate (ATP) activatable CEL-Fe(III) chelate was designed, synthesized, and then encapsulated with a reactive oxygen species (ROS)-responsive polymer to obtain CEL-Fe nanoparticles (CEL-Fe NPs). In normal tissues, CEL-Fe NPs maintain structural stability and exhibit reduced systemic toxicity, while at the tumor site, an ATP-ROS-rich tumor microenvironment, drug release is triggered by ROS, and antitumor potency is restored by competitive binding of ATP. This intelligent CEL delivery system improves the biosafety and bioavailability of CEL for cancer therapy. Such a CEL-metal chelate strategy not only mitigates the challenges associated with CEL but also opens avenues for the generation of CEL derivatives, thereby expanding the therapeutic potential of CEL in clinical settings.

Probing the structural evolution on the surface of cardiolipin vesicles with an amphiphilic second harmonic generation and fluorescence probe.

Investigating the influence of the ambient chemical environment on molecular behaviors in liposomes is crucial for understanding and manipulating cellular vitality as well as the capabilities of lipid drug carriers in various environments. Here, we designed and synthesized a second harmonic generation (SHG) and fluorescence probe molecule called Pyr-Py+-N+ (PPN), which possesses membrane-targeting capability. We employed PPN to investigate the response of lipid vesicles composed of cardiolipin to the presence of exogenous salt. The kinetic behaviors, including the adsorption and embedding of PPN on the surface of small unilamellar vesicles (SUVs) composed of cardiolipin, were analyzed. The response of the SUVs to the addition of NaCl was also monitored. A rapid decrease in vesicle size can be evidenced through the rapid drop in SHG emission originating from PPN located on the vesicle surface.

Self-templating synthesis strategy of oxygen-doped carbon from unique wasted pulping liquid directly as a cathode material for high-performance zinc ion hybrid capacitors.

Affinity and storage capacity for zinc ions of the electrode materials are crucial factors on the properties of zinc ion hybrid capacitors (ZHICs). Wasted pulping liquor with abundant carbohydrates, lignin and inorganic matter served as a unique precursor to produce embedded oxygen-doped hierarchical porous carbon directly through a one-step carbonization process in this investigation. In carbonization process, lignin can serve effectively as the carbon framework, carbohydrates not only act as sacrificial templates but also offer a plentiful oxygen source which can increase the affinity for Zn2+, and sodium-containing inorganic substances plays a role as hard templates to optimize the pore structure. The resulting porous carbon under carbonization temperature of 800 °C shows a high specifical area of 2186 m2g-1 with oxygen content of 4.8 %, which can reduce the adsorption energy of Zn2+ from -0.16 eV to -0.32 eV through electrochemical techniques and density functional theory (DFT) calculations, the incorporation of oxygen was demonstrated to enhance the adsorption and desorption kinetics of Zn2+, suggesting a bright future for application in the domain of energy storage. The resulting ZIHC assembly showcases a notable energy density of 84.6 Wh kg-1 at a power density of 359 W kg-1. Remarkably, even after 10,000 charge and discharge cycles, it exhibits exceptional cycle stability with retaining 86.56 % of its capacity. Consequently, this approach provides fresh insights for exploring the facile and commercial fabrication of biomass-derived cathodes for ZIHCs, thereby propelling the progress of eco-friendly energy storage devices.

Digital Light 3D Printing of Double Thermoplastics with Customizable Mechanical Properties and Versatile Reprocessability.

Digital light processing (DLP) is a 3D printing technology offering high resolution and speed. Printable materials are commonly based on multifunctional monomers, resulting in the formation of thermosets that usually cannot be reprocessed or recycled. Some efforts are made in DLP 3D printing of thermoplastic materials. However, these materials exhibit limited and poor mechanical properties. Here, a new strategy is presented for DLP 3D printing of thermoplastics based on a sequential construction of two linear polymers with contrasting (stiff and flexible) mechanical properties. The inks consist of two vinyl monomers, which lead to the stiff linear polymer, and α-lipoic acid, which forms the flexible linear polymer via thermal ring-opening polymerization in a second step. By varying the ratio of stiff and flexible linear polymers, the mechanical properties can be tuned with Young's modulus ranging from 1.1 GPa to 0.7 MPa, while the strain at break increased from 4% to 574%. Furthermore, these printed thermoplastics allow for a variety of reprocessability pathways including self-healing, solvent casting, reprinting, and closed-loop recycling of the flexible polymer, contributing to the development of a sustainable materials economy. Last, the potential of the new material in applications ranging from soft robotics to electronics is demonstrated.

"Top-down" overexpression optimization of butelase-1 in Escherichia coli and its application in anti-tumor peptides.

Butelase-1, the fastest known Asn/Asp-specific peptide ligase capable of catalyzing peptide ligation and cyclization, holds promising application prospects in the fields of food and biology. However, limited research exists on its recombinant expression and potential applications in peptide drugs. In this study, the activity of recombinantly-produced butelase-1 was enhanced by co-expressing it with a molecular chaperone in the SHuffle T7 strain. By introducing single or multiple synonymous rare codons at the beginning of the coding regions of beta-strand or alpha-helix, in combination with ribosomal binding site engineering, the activity of butelase-1 could be further improved. Consequently, the butelase-1 with a specific activity of 386.93 U/mg and a catalytic efficiency of 11,048 M-1 s-1 was successfully prepared in E. coli, resulting in a total activity of 8183.54 U/L and a yield of about 100 mg/L. This optimized butelase-1 was then used to efficiently cyclize the redesigned anti-cancer peptide lunasin, leading to enhanced bioavailability and anti-cancer effects. Overall, this study not only provided valuable biotechnology strategies for improving the recombinant expression of butelase-1 but also demonstrated a successful application for enhancing the biological efficacy of anti-cancer peptides.