A soft microrobot with highly deformable 3D actuators for climbing and transitioning complex surfaces.

The climbing microrobots have attracted growing attention due to their promising applications in exploration and monitoring of complex, unstructured environments. Soft climbing microrobots based on muscle-like actuators could offer excellent flexibility, adaptability, and mechanical robustness. Despite the remarkable progress in this area, the development of soft microrobots capable of climbing on flat/curved surfaces and transitioning between two different surfaces remains elusive, especially in open spaces. In this study, we address these challenges by developing voltage-driven soft small-scale actuators with customized 3D configurations and active stiffness adjusting. Combination of programmed strain distributions in liquid crystal elastomers (LCEs) and buckling-driven 3D assembly, guided by mechanics modeling, allows for voltage-driven, complex 3D-to-3D shape morphing (bending angle > 200°) at millimeter scales (from 1 to 10 mm), which is unachievable previously. These soft actuators enable development of morphable electroadhesive footpads that can conform to different curved surfaces and stiffness-variable smart joints that allow different locomotion gaits in a single microrobot. By integrating such morphable footpads and smart joints with a deformable body, we report a multigait, soft microrobot (length from 6 to 90 mm, and mass from 0.2 to 3 g) capable of climbing on surfaces with diverse shapes (e.g., flat plane, cylinder, wavy surface, wedge-shaped groove, and sphere) and transitioning between two distinct surfaces. We demonstrate that the microrobot could navigate from one surface to another, recording two corresponding ceilings when carrying an integrated microcamera. The developed soft microrobot can also flip over a barrier, survive extreme compression, and climb bamboo and leaf.

The transcription factor PbrMYB24 regulates lignin and cellulose biosynthesis in stone cells of pear fruits.

Lignified stone cell content is a key factor used to evaluate fruit quality, influencing the economic value of pear (Pyrus pyrifolia) fruits. However, our understanding of the regulatory networks of stone cell formation is limited due to the complex secondary metabolic pathway. In this study, we used a combination of co-expression network analysis, gene expression profiles, and transcriptome analysis in different pear cultivars with varied stone cell content to identify a hub MYB gene, PbrMYB24. The relative expression of PbrMYB24 in fruit flesh was significantly correlated with the contents of stone cells, lignin, and cellulose. We then verified the function of PbrMYB24 in regulating lignin and cellulose formation via genetic transformation in homologous and heterologous systems. We constructed a high-efficiency verification system for lignin and cellulose biosynthesis genes in pear callus. PbrMYB24 transcriptionally activated multiple target genes involved in stone cell formation. On the one hand, PbrMYB24 activated the transcription of lignin and cellulose biosynthesis genes by binding to different cis-elements [AC-I (ACCTACC) element, AC-II (ACCAACC) element and MYB-binding sites (MBS)]. On the other hand, PbrMYB24 bound directly to the promoters of PbrMYB169 and NAC STONE CELL PROMOTING FACTOR (PbrNSC), activating the gene expression. Moreover, both PbrMYB169 and PbrNSC activated the promoter of PbrMYB24, enhancing gene expression. This study improves our understanding of lignin and cellulose synthesis regulation in pear fruits through identifying a regulator and establishing a regulatory network. This knowledge will be useful for reducing the stone cell content in pears via molecular breeding.

Advanced Smart Biomaterials for Regenerative Medicine and Drug Delivery Based on Phosphoramidite Chemistry: From Oligonucleotides to Precision Polymers.

Over decades of development, while phosphoramidite chemistry has been known as the leading method in commercial synthesis of oligonucleotides, it has also revolutionized the fabrication of sequence-defined polymers (SDPs), offering novel functional materials in polymer science and clinical medicine. This review has introduced the evolution of phosphoramidite chemistry, emphasizing its development from the synthesis of oligonucleotides to the creation of universal SDPs, which have unlocked the potential for designing programmable smart biomaterials with applications in diverse areas including data storage, regenerative medicine and drug delivery. The key methodologies, functions, biomedical applications, and future challenges in SDPs, have also been summarized in this review, underscoring the significance of breakthroughs in precisely synthesized materials.

Sleep deprivation boosts O2·- levels in the brains of mice as visualized by a Golgi apparatus-targeted ratiometric fluorescence nanosensor.

Sleep deprivation (SD) is highly prevalent in the modern technological world. Emerging evidence shows that sleep deprivation is associated with oxidative stress. At the organelle level, the Golgi apparatus actively participates in the stress response. In this study, to determine whether SD and Golgi apparatus stress are correlated, we rationally designed and fabricated a novel Golgi apparatus-targeted ratiometric nanoprobe called Golgi dots for O2·- detection. This probe exhibits high sensitivity and selectivity in cells and brain slices of sleep-deprived mice. Golgi dots can be readily synthesized by coprecipitation of Golgi-F127, an amphiphilic polymer F127 modified with a Golgi apparatus targeting moiety, caffeic acid (CA), the responsive unit for O2·-, and red emissive carbon nanodots (CDs), which act as the reference signal. The fluorescence emission spectrum of the developed nanoprobe showed an intense peak at 674 nm, accompanied by a shoulder peak at 485 nm. As O2·- was gradually added, the fluorescence at 485 nm continuously increased; in contrast, the emission intensity at 674 nm assigned to the CDs remained constant, resulting in the ratiometric sensing of O2·-. The present ratiometric nanoprobe showed high selectivity for O2·- monitoring due to the specific recognition of O2·- by CA. Moreover, the Golgi dots exhibited good linearity with respect to the O2·- concentration within 5 to 40 µM, and the limit of detection (LOD) was ~ 0.13 µM. Additionally, the Golgi dots showed low cytotoxicity and an ability to target the Golgi apparatus. Inspired by these excellent properties, we then applied the Golgi dots to successfully monitor exogenous and endogenous O2·- levels within the Golgi apparatus. Importantly, with the help of Golgi dots, we determined that SD substantially elevated O2·- levels in the brain.

Nitrogen-doped activated carbon-based steel slag composite material as an accelerant for enhancing the resilience of flexible biogas production process against shock loads: Performance, mechanism and modified ADM1 modeling.

Anaerobic digestion for flexible biogas production can lead to digestion inhibition under high shock loads. While steel slag addition has shown promise in enhancing system buffering, its limitations necessitate innovation. This study synthesized the nitrogen-doped activated carbon composite from steel slag to mitigate intermediate product accumulation during flexible biogas production. Material characterization preceded experiments introducing the composite into anaerobic digestion systems, evaluating its impact on methane production efficiency under hydraulic and concentration sudden shocks. Mechanistic insights were derived from microbial community and metagenomic analyses, facilitating the construction of the modified Anaerobic Digestion Model No. 1 (ADM1) to quantitatively assess the material's effects. Results indicate superior resistance to concentration shocks with substantial increment of methane production rate up to 33.45% compared with control group, which is mediated by direct interspecies electron transfer, though diminishing with increasing shock intensity. This study contributes theoretical foundations for stable flexible biogas production and offers an effective predictive tool for conductor material reinforcement processes.

Auxin inhibits lignin and cellulose biosynthesis in stone cells of pear fruit via the PbrARF13-PbrNSC-PbrMYB132 transcriptional regulatory cascade.

Stone cells are often present in pear fruit, and they can seriously affect the fruit quality when present in large numbers. The plant growth regulator NAA, a synthetic auxin, is known to play an active role in fruit development regulation. However, the genetic mechanisms of NAA regulation of stone cell formation are still unclear. Here, we demonstrated that exogenous application of 200 µM NAA reduced stone cell content and also significantly decreased the expression level of PbrNSC encoding a transcriptional regulator. PbrNSC was shown to bind to an auxin response factor, PbrARF13. Overexpression of PbrARF13 decreased stone cell content in pear fruit and secondary cell wall (SCW) thickness in transgenic Arabidopsis plants. In contrast, knocking down PbrARF13 expression using virus-induced gene silencing had the opposite effect. PbrARF13 was subsequently shown to inhibit PbrNSC expression by directly binding to its promoter, and further to reduce stone cell content. Furthermore, PbrNSC was identified as a positive regulator of PbrMYB132 through analyses of co-expression network of stone cell formation-related genes. PbrMYB132 activated the expression of gene encoding cellulose synthase (PbrCESA4b/7a/8a) and lignin laccase (PbrLAC5) binding to their promotors. As expected, overexpression or knockdown of PbrMYB132 increased or decreased stone cell content in pear fruit and SCW thickness in Arabidopsis transgenic plants. In conclusion, our study shows that the 'PbrARF13-PbrNSC-PbrMYB132' regulatory cascade mediates the biosynthesis of lignin and cellulose in stone cells of pear fruit in response to auxin signals and also provides new insights into plant SCW formation.

Periodontitis is associated with stroke.

BACKGROUND: Periodontitis is considered as a risk factor for cardiovascular diseases and atherosclerosis. However, the relationship between periodontitis and stroke is rarely studied. Therefore, we aimed to explore the relationship between periodontitis and stroke. METHODS: Statistical analysis was performed using the complex sampling design. We analyzed data on 6,460 participants, representing 92,856,028 American citizens aged 30 years or older, who had valid data on periodontitis and stroke from the National Health and Nutrition Examination Survey 2009-2014. We used clinical attachment level and probing pocket depth precisely to determine periodontitis and it is the first time to use such a precise method for exploring the relationship between periodontitis and stroke. RESULTS: 39.9% of participants had periodontitis and 2.1% of participants had a record of stroke diagnosis. Stroke was associated with severity levels of periodontitis (p for trend = 0.018). The odds ratio for stroke was significantly elevated in the severe periodontitis and moderate periodontitis participants compared to participants without periodontitis (OR for severe periodontitis: 2.55, 95% CI 1.25-5.21; OR for moderate periodontitis: 1.71, 95% CI 1.17-2.50). After adjusting for race/ethnicity and sex, the association remained significant (p for trend = 0.009). After further adjusting for BMI, hypercholesterolemia, diabetes, alcohol consumption and physical activity, the association still existed (p for trend = 0.027). The association was significant consistently after further adjusting for age (p for trend = 0.033). CONCLUSIONS: In this nationally representative study, we found an association between periodontitis and stroke. The risk of stroke in participants with severe periodontitis and moderate periodontitis was 2.55 times and 1.71times as high as those without periodontitis. Dental health management may be of benefit to stroke prevention.

Conjugated Polymer Nanoparticles for Tumor Theranostics.

Water-dispersible conjugated polymer nanoparticles (CPNs) have demonstrated great capabilities in biological applications, such as in vitro cell/subcellular imaging and biosensing, or in vivo tissue imaging and disease treatment. In this review, we summarized the recent advances of CPNs used for tumor imaging and treatment during the past five years. CPNs with different structures, which have been applied to in vivo solid tumor imaging (fluorescence, photoacoustic, and dual-modal) and treatment (phototherapy, drug carriers, and synergistic therapy), are discussed in detail. We also demonstrated the potential of CPNs as cancer theranostic nanoplatforms. Finally, we discussed current challenges and outlooks in this field.

Marine biomaterials in biomedical nano/micro-systems.

Marine resources in unique marine environments provide abundant, cost-effective natural biomaterials with distinct structures, compositions, and biological activities compared to terrestrial species. These marine-derived raw materials, including polysaccharides, natural protein components, fatty acids, and marine minerals, etc., have shown great potential in preparing, stabilizing, or modifying multifunctional nano-/micro-systems and are widely applied in drug delivery, theragnostic, tissue engineering, etc. This review provides a comprehensive summary of the most current marine biomaterial-based nano-/micro-systems developed over the past three years, primarily focusing on therapeutic delivery studies and highlighting their potential to cure a variety of diseases. Specifically, we first provided a detailed introduction to the physicochemical characteristics and biological activities of natural marine biocomponents in their raw state. Furthermore, the assembly processes, potential functionalities of each building block, and a thorough evaluation of the pharmacokinetics and pharmacodynamics of advanced marine biomaterial-based systems and their effects on molecular pathophysiological processes were fully elucidated. Finally, a list of unresolved issues and pivotal challenges of marine-derived biomaterials applications, such as standardized distinction of raw materials, long-term biosafety in vivo, the feasibility of scale-up, etc., was presented. This review is expected to serve as a roadmap for fundamental research and facilitate the rational design of marine biomaterials for diverse emerging applications.

Natural ursolic acid based self-therapeutic polymer as nanocarrier to deliver natural resveratrol for natural therapy of acute kidney injury.

Acute kidney injury (AKI) is a common kidney disease associated with excessive reactive oxygen species (ROS). Unfortunately, due to the low kidney targeting and undesired side effects, the existing antioxidant and anti-inflammatory drugs are unavailable for AKI management in clinic. Therefore, it's essential to develop effective nanodrugs with high renal targeting and biocompatibility for AKI treatment. Herein, we reported a novel nanodrug for AKI treatment, utilizing poly(ursolic acid) (PUA) as a bioactive nanocarrier and resveratrol (RES) as a model drug. The PUA polymer was synthesized form ursolic acid with intrinsic antioxidant and anti-inflammatory activities, and successfully encapsulated RES through a nanoprecipitation method. Subsequently, we systemically investigated the therapeutic potential of RES-loaded PUA nanoparticles (PUA NPs@RES) against AKI. In vitro results demonstrated that PUA NPs@RES effectively scavenged ROS and provided substantial protection against H2O2-induced cellular damage. In vivo studies revealed that PUA NPs significantly improved drug accumulation in the kidneys and exhibited favorable biocompatibility. Furthermore, PUA NPs alone exhibited additional anti-inflammatory and antioxidant effect, synergistically enhancing therapeutic efficacy in AKI mouse models when combined with RES. Overall, our study successfully developed an effective nanodrug using self-therapeutic nanocarriers, presenting a promising option for the treatment of AKI.

First report of Calonectria ilicicola causing fruit rot on postharvest Prunus persica in Zhejiang Province, China.

Peach (Prunus persica) is an important economic tree fruit in China, with 15 million tons produced in 2020 (Xu et al. 2022). In September 2021, fruit rot on postharvest P. persica 'Yingqingtao' was observed in an orchard warehouse in Qixing district (120°41'E, 29°15'N), Zhejiang Province. Disease incidence was estimated at 25%, and yield loss was estimated at approximately 20% of the total yield. The naturally infected fruit had water-soaked, light brown lesions that fused, and produced a gray-white, dense mycelium (Fig. 1 A). The mycelia were transferred using a sterilized toothpick to potato dextrose agar (PDA) and cultured for 7 d. Macroconidia were used to produce five single-spore isolates, each from a different fruit. Six-day-old colonies grown on PDA at 26°C had light brown centers with gray-white edges; on the underside the centers were reddish brown and white towards the margin (Fig. 1 D). Isolate TGF2 was selected for further identification. Macroconidia were hyaline, straight, cylindrical, and one-to-three septae, 63.2 to 81.8 × 5.7 to 7.8 µm (mean = 73.9 ± 4.3 × 6.9 ± 0.5, n = 30) (Fig. 1 E). Chlamydospores were produced abundantly on PDA (Fig. 1 F), and measured 11.7 to 19.4 × 8.5 to 16.9 µm (n = 10). Perithecia were reddish orange, globose, and 329.9 to 417.1 µm in diameter on PDA (Fig. 1 G). Asci were hyaline and clavate, 61.2 to 91.8 × 14.4 to 20.7 µm (n = 10); ascospores were hyaline, slightly curved, 1- to 3-septate, mostly 1-septate, and 37.6 to 59.7 × 4.9 to 6.4 µm (mean = 49.9 ± 4.5 × 5.6 ± 0.4, n = 30) (Fig. 1 H-J). Morphological characteristics placed this organism within the Ca. kyotensis species complex (Liu et al. 2020). For molecular identification, the internal transcribed spacer (ITS: OP164807-OP164811), calmodulin (Cal: OP176049-OP176053), histone3 (His3: OP176054-OP176058), and translation elongation factor 1α (Tef1: OP176044-OP176048) genes were sequenced (Liu, et al., 2020). The twenty sequences were deposited in GenBank. A BLAST search of these sequences showed 99% identity with sequences of the ex-holotype Ca. ilicicola CMW 30998 (Liu et al. 2020). Bayes phylogenesis suggested that these strains and Ca. ilicicola CMW 30998 were clustered in the same clade (Bayesian posterior probability = 1) (Fig. 2). Integrating morphology and molecular data, these strains were identified as Ca. ilicicola. For pathogenicity tests, P. persica fruits were surface sterilized in 75% ethanol for 30 s and air-dried for 5 mins to allow the alcohol to volatilize. A conidial suspension (30 mL of 1 × 106 conidia/mL) of TGF2 was sprayed onto ten fruits, and ten fruits sprayed with sterilized water served as controls. The experiment was repeated three times. Fruits were kept on a mist bench at 26°C and 60% relative humidity. After 5 days, inoculated fruits showed necrotic lesions and a dense, gray-white mycelium, however, the control fruits showed no symptoms (Fig. 1 B, C). Ca. ilicicola was reisolated from lesions of inoculated fruits. Ca. ilicicola has been reported from Vaccinium sp., Glycine max, Medicago sativa (Farr and Rossman 2022; Kleczewski et al. 2019; Zhang et al. 2020). To our knowledge, this is the first report of Ca. ilicicola causing fruit rot of P. persica in China. In other research on Ca. ilicicola, we found that continuous light could inhibit its growth, suggesting a method to protect postharvest peaches.

First report of Fusarium solani causing Fusarium wilt of Bletilla striata (hyacinth orchid) in Zhejiang province of China.

Bletilla striata, a member of the family Orchidaceae, is a perennial herbaceous plant used in Chinese medicine. It is a commonly cultivated economic crop in the Yangtze River Basin provinces of China, as its roots are used to treat bleeding and inflammation. In Zhejiang province, Bletilla striata has a planting area of 1400 hectares with a total production of approximately 2.6×106 kg. In October 2021, over 40% of B. striata plants showed severe wilt in a traditional Chinese medicine plantation (ca. 10 ha) in Xianju City, Zhejiang Province, China. In July, leaf curling, crinkling, and leaf-edge browning of the diseased plants were first noticed in the field. Then, necrotic streaks gradually spread to the roots. Stems displayed chlorosis and withering and when they were cut vertically, symptoms such as vascular bundle discoloration, appeared. After October, the individual plants slowly wilted and died, their aboveground parts became filamentous, and the epidermis detached from the corm's fibrous roots. Diseased plants were easily removed as the corm root had fractured. White mycelia were clearly seen in the stem. Three symptomatic leaves and three stems were cut, their surfaces disinfected, and plated on potato dextrose agar (PDA). Six strains were subsequently isolated from all samples. Fungal colonies with white to cream-colored mycelia from all tissues appeared after 3 d of incubation at 26 °C. Pure cultures obtained after monospore isolation were examined for their morphological characteristics. The colonies grew rapidly, were fluffy and appressed, and had cottony white to pale cream coloration. Microconidia were hyaline, oval to reniform, with zero or one-septate (4.0-12.0 × 1.0-5.5 µm), and usually formed on elongated monophialidic conidiogenous cells. Macroconidia were wide, fusiform, or slightly curved with one or three septa (23.0-36.0 × 4.5-7.0 µm). Chlamydospores were spherical and were abundant on carrot agar (CA) medium within 2 wk. Fresh mycelia and conidia that grew at 26 ℃ for 7 d were collected from PDA plates. Next, DNA was extracted using the Ezup Column Fungi Genomic DNA Purification kit (Sangon Biotech, Shanghai, China). We amplified a portion of RNA polymerase II second largest subunit gene (RPB2) using primers 5f2/7cr (O'Donnell et al. 2010), the internal transcribed spacer (ITS) region using primers ITS1F/ITS4 (White et al. 1990), and the partial translation elongation factor-1α gene using primers EF1/ EF2 (O'Donnell et al. 1998) from the genomic DNA and sent the PCR amplicons for sequencing at Tsingke Biotechnology Co., Ltd., Wuhan, China. A BLAST search of the obtained sequences (GenBank accessions OP743920, OP913183, and OP913180) showed 99-100% homology with the respective sequences of the Fusarium solani reference isolate NRRL46702 (O'Donnell et al. 2008). Based on the morphological and molecular characteristics and BLAST search, the fungus was identified as F. solani (Leslie and Summerell 2006). Pathogenicity of the purified F. solani isolate was assessed by inoculateing a F. solani spore suspension of 1×106 conidia/mL (20 mL per seedling) on corm wounds made with a toothpick. Four inoculated and three non-inoculated seedlings (sterilized water as a negative control) were grown in a greenhouse at 26 °C under natural sunlight and covered with plastic bags to maintain humidity for 72 h. After 15 d, leaf browning on leaf edges, new leaf bases, and corm epidermis was observed. Symptoms, similar to those detected in the original sample, developed on the inoculated leaves, whereas the controls remained asymptomatic. Fusarium solani was successfully re-isolated from all four inoculated seedlings, and their identity confirmed by generating partial Tef1 and RPB2 sequences, thereby fulfilling the Koch's postulate. To our knowledge, F. solani has not been previously reported as a pathogen of B. striata.

The Preparation of Golgi Apparatus-Targeted Polymer Dots Encapsulated with Carbon Nanodots of Bright Near-Infrared Fluorescence for Long-Term Bioimaging.

As a vital organelle in eukaryotic cells, the Golgi apparatus is responsible for processing and transporting proteins in cells. Precisely monitoring the status of the Golgi apparatus with targeted fluorescence imaging technology is of enormous importance but remains a dramatically challenging task. In this study, we demonstrate the construction of the first Golgi apparatus-targeted near-infrared (NIR) fluorescent nanoprobe, termed Golgi-Pdots. As a starting point of our investigation, hydrophobic carbon nanodots (CNDs) with bright NIR fluorescence at 674 nm (fluorescence quantum yield: 12.18%), a narrow emission band of 23 nm, and excellent stability were easily prepared from Magnolia Denudata flowers using an ultrasonic method. Incorporating the CNDs into a polymer matrix modified with Golgi-targeting molecules allowed for the production of the water-soluble Golgi-Pdots, which showed high colloidal stability and similar optical properties compared with pristine CNDs. Further studies revealed that the Golgi-Pdots showed good biocompatibility and Golgi apparatus-targeting capability. Based on these fascinating merits, utilizing Golgi-Pdots for the long-term tracking of the Golgi apparatus inside live cells was immensely successful.

Factors affecting the efficacy of Invisalign in anterior tooth rotation.

INTRODUCTION: The objectives of this study were to evaluate the clinical efficacy of SmartTrack aligner in rotational movement of the anterior tooth by 15°-30°, and to analyze the factors influencing anterior tooth rotational movement. METHODS: A total of 212 teeth, including 4 tooth types (maxillary central incisor, maxillary lateral incisor, mandibular central incisor, and mandibular canine) that require anterior tooth rotational movement by 15°-30° were selected from 123 patients, with a mean age of 25.6 years. Rotational movements were calculated from the superimposition of the initial and predicted models (predicted rotational movement) and from the superimposition of the initial and achieved models (achieved rotational movement) using the best-fit alignment tool in NX Imageware. The difference between the predicted and achieved rotational movements (DPARM) was calculated. Univariate analysis, categorical regression analysis, and subgroup analysis were performed on 7 variables: age, gender, tooth type, predicted rotational movement, attachment type, interproximal reduction (IPR), and the total number of active aligners. RESULTS: The mean DPARM when the anterior tooth was rotated 15°-30° was 4.46° (range, -3.52° to 25.28°). Regression analysis showed that the patient's age, IPR, tooth type, and predicted rotational movement affected DPARM (P <0.01). CONCLUSIONS: Factors influencing the DPARM of the anterior tooth include the patient's age, tooth type, the magnitude of the predicted rotational movement, and whether or not IPR was prescribed.

Harnessing 4D Printing Bioscaffolds for Advanced Orthopedics.

The development of programmable functional biomaterials makes 4D printing add a new dimension, time (t), based on 3D structures (x, y, z), therefore, 4D printed constructs could transform their morphology or function over time in response to environmental stimuli. Nowadays, highly efficient bone defect repair remains challenging in clinics. Combining programmable biomaterials, living cells, and bioactive factors, 4D bioprinting provides greater potential for constructing dynamic, personalized, and precise bone tissue engineering scaffolds by complex structure formation and functional maturation. Therefore, 4D bioprinting has been regarded as the next generation of bone repair technology. This review focuses on 4D printing and its advantages in orthopedics. The applications of different smart biomaterials and 4D printing strategies are briefly introduced. Furthermore, one summarizes the recent advancements of 4D printing in bone tissue engineering, uncovering the addressed and unaddressed medical requirements. In addition, current challenges and future perspectives are further discussed, which will offer more inspiration about the clinical transformation of this emerging 4D bioprinting technology in bone regeneration.

A self-assembled leucine polymer sensitizes leukemic stem cells to chemotherapy by inhibiting autophagy in acute myeloid leukemia.

Chemotherapy is the primary treatment option for acute myeloid leukemia (AML), but leukemic stem cells (LSC) can survive chemotherapy for disease recurrence and refractory. Here, we found that AML cells obtained from relapsed patients had increased autophagy levels than de novo AML cells. Furthermore, doxorubicin (DOX) treatment stimulated autophagy in LSC by repressing the mTOR pathway, and pharmaceutical inhibition of autophagy rendered chemoresistant LSC sensitive to DOX treatment in MLL-AF9 induced murine AML. Moreover, we developed a self-assembled leucine polymer, which activated mTOR to inhibit autophagy in AML cells by releasing leucine. The leucine polymer loaded DOX (Leu-DOX) induced much less autophagy but more robust apoptosis in AML cells than the DOX treatment. Notably, the leucine polymer and Leu-DOX were specifically taken up by AML cells and LSC but not by normal hematopoietic cells and hematopoietic stem/progenitor cells in the bone marrow. Consequently, Leu-DOX efficiently reduced LSC and prolonged the survival of AML mice, with more limited myeloablation and tissue damage side effects than DOX treatment. Overall, we proposed that the newly developed Leu-DOX is an effective autophagy inhibitor and an ideal drug to efficiently eliminate LSC, thus serving as a revolutionary strategy to enhance the chemotherapy efficacy in AML.

Recent Advances of Poly(ester amide)s-Based Biomaterials.

Biodegradable and biocompatible biomaterials have offered much more opportunities from an engineering standpoint for treating diseases and maintaining health. Poly(ester amide)s (PEAs), as an outstanding family among such biomaterials, have risen overwhelmingly in the past decades. These synthetic polymers have easily and widely available raw materials and a diversity of synthetic approaches, which have attracted considerable attention. More importantly, combining the superiorities of polyamides and polyesters, PEAs have emerged with better functions. They could have improved biodegradability, biocompatibility, and cell-material interactions. The PEAs derived from α-amino acids even allow the introduction of pendant sites for further modification or functionalization. Meanwhile, it is gradually recognized that the chemical structures are closely related to the physiochemical and biological properties of PEAs so that their properties can be precisely controlled. PEAs therefore become significant materials in the biomedical fields. This review will attempt to summarize the recent progress in the development of PEAs with respect to the preparation materials and methods, structure-property relationships along with their latest biomedical accomplishments, especially for drug delivery and tissue engineering.

Poly(disulfide)s: From Synthesis to Drug Delivery.

Bioresponsive polymers have been widely used in drug delivery because of their degradability. For example, poly(disulfide)s with repeating disulfide bonds in the main chain have attracted considerable research attention. The characteristics of the disulfide bonds, including their dynamic and reversible properties and their responsiveness to stimuli such as reductants, light, heat, and mechanical force, make them ideal platforms for on-demand drug delivery. This review introduces the synthesis methods and applications of poly(disulfide)s. Furthermore, the synthesis methods of poly(disulfide)s are classified on the basis of the monomers used: oxidative step-growth polymerization with dithiols, ring-opening polymerization with cyclic disulfides, and polymerization with linear disulfides. In addition, recent advances in poly(disulfide)s for the delivery of small-molecule or biomacromolecular drugs are discussed. Quantum-dot-loaded poly(disulfide) delivery systems for imaging are also included. This review provides an overview of the various design strategies employed in the construction of poly(disulfide) platforms to inspire new applications in the field of drug delivery.

Effect of water chemistry on nitrogen transformation, dissolved organic matter composition and microbial community structure in hyporheic zone sediment columns.

Controlled surface water systems, including those with dams lead to dynamic stage changes that alter the fluctuation directions of flow exchange in the hyporheic zones (HZ). However, the nitrogen transformation, dissolved organic matter (DOM) composition, and microbial community responding to variable scenarios of water source and hyporheic exchange are poorly studied. The present work investigated nitrogen transformation in HZ sediments, focusing on how microbial community structure and biological functions related to nitrogen transformation and sediment-attached DOM compositions. Upwelling of synthesized groundwater, downwelling of synthesized river water and exchangeable elution of both feed water created distinct microbial zonation and N-transformation processes. Mixing of river water and groundwater enhanced microbial diversity, microbial co-occurrence network complexity and N-transformation functions. In terms of the sediment-attached DOM properties after hyporheic exchanges, humic fractions occupied the predominant chromophoric DOM. Correlation analysis implied that there were more DOM properties, e.g., tryptophan-like proteins, humic-like fractions, and the source of humic fractions, involved in affecting the microbial community under downwelling flow. Co-occurrence network analysis verified that fluorescent components, protein-like and lignin-like fractions in sediment-detached DOM were clustered with microbial communities in one module in downwelling column, implying closer interactions among microbial communities and DOM fractions. The strains of Nitrospinae, Dinghuibacter, and Lentimicrobium etc. were key species collaborating to metabolize both nitrogen and DOM in HZ sediments. The work provides insights into how the nitrogen transformation, DOM compositional changes, as well as the linkages between community structure and DOM factions, response to the changes in water chemistry, leading to valuable insights into hyporheic zone functions.

Adsorption of Cu2+ by UV aged polystyrene in aqueous solution.

Microplastics are the critical carriers of heavy metals in the environment. Thus, investigating the adsorption mechanisms between the microplastics and heavy metals is helpful to understand the migration and transformation pattern of the heavy metals in the environment. The adsorption of microplastics towards heavy metals can be largely affected by natural aging (e.g., UV-aging), environmental pH, and salinity. In this study, the adsorption of polystyrene (PS) towards Cu2+ and the effects of UV-aging, environment pH, and salinity on the adsorption were systematically investigated. The results show that the adsorption capacity of PS towards Cu2+ increased with the UV-aging time, as UV-aging increased the microcracks and oxygen-containing functional groups on the surface of the PS. Adsorption kinetics data followed the pseudo-second-order model, indicating that the interaction between PS and Cu2+ is chemical adsorption. Adsorption isotherms data could be well-described by both the Langmuir and Freundlich models, indicating that the adsorption was multilayer adsorption. As the solution pH and salinity can influence the surface charge of the PS, they could also affect the performance of the PS on Cu2+ adsorption. High pH facilitated the adsorption of PS towards Cu2+, while high salinity (above 1‰) inhibited the adsorption.