Decitabine as epigenetic priming with CLAG induce improved outcome of relapsed or refractory acute myeloid leukemia in children.

BACKGROUND: Decitabine (DAC), a DNA methyltransferase inhibitor, has shown efficacy combined with chemotherapy for relapsed or refractory (R/R) acute myeloid leukemia (AML) in adults, but less is known about its efficacy in children. Accordingly, we conducted a study which involved a priming regimen consisting of DAC with cladribine, cytarabine, and granulocyte-stimulating factor (DAC-CLAG) and compared the efficacy and safety of this regimen with CLAG alone. METHODS: A total of 39 R/R AML children who received the CLAG or DAC-CLAG regimen in Shanghai Children's Hospital were retrospectively enrolled in this non-randomized study. These regimens were studied sequentially over time. Twenty-two patients received CLAG from 2015, while 17 patients were administered epigenetic priming with DAC before CLAG from 2020. Patients were subsequently bridged to stem cell transplantation (SCT) or consolidation chemotherapy. Complete remission (CR) and adverse effects were analyzed by Fisher's exact test, and survival was analyzed by the Kaplan-Meier method. RESULTS: DAC-CLAG conferred a numerically higher CR compared to CLAG (70.59% vs 63.64%; P = 0.740). High CR rates occurred in patients with good cytogenetics (P = 0.029) and prior induction without cladribine (P = 0.099). The 1-year event-free survival (EFS) was 64.71% ± 11.59% and 63.31% ± 10.35% in the DAC-CLAG and CLAG group (P = 0.595), and 1-year overall survival (OS) was 81.45% ± 9.72% and 77.01% ± 9.04%, respectively (P = 0.265). The 1-year OS and EFS after SCT were higher in the DAC-CLAG than in the CLAG cohort (100% vs 92.31% ± 7.39%, P = 0.072; 92.31% ± 7.39% vs 85.71% ± 9.35%, P = 0.158). Univariate analysis revealed that a good prognosis included good cytogenetics (P = 0.002), non-complex karyotype (P = 0.056), CR on reinduction (P < 0.0001), and bridging to SCT (P = 0.0007). Use of a hypomethylating agent (P = 0.049) and bridging to SCT (P = 0.011) were independent prognostic factors. Grade 3/4 hematologic toxicity and infection were the main adverse events. CONCLUSIONS: DAC prior to the CLAG regimen improved remission in pediatric R/R AML, and was feasible and well tolerated. CLAG ± DAC as a salvage therapy prior to SCT induced improved survival.

GASZ is indispensable for gametogenesis in the silkworm, Bombyx mori.

The prominent role of the P-element induced wimpy testis (PIWI)-interacting RNA (piRNA) pathway in animals is to silence transposable elements and maintain genome stability, ensuring proper gametogenesis in gonads. GASZ (Germ cell protein with Ankyrin repeats, Sterile alpha motif, and leucine Zipper) is an evolutionarily conserved protein located on the outer mitochondrial membrane of germ cells and plays vital roles in the piRNA pathway and spermatogenesis in mammals. In the model insect Drosophila melanogaster, GASZ is essential for piRNA biogenesis and oogenesis, whereas its biological functions in non-drosophilid insects are still unknown. Here, we describe a comprehensive investigation of GASZ functions in the silkworm, Bombyx mori, a lepidopteran model insect, by using a binary transgenic CRISPR/Cas9 system. The BmGASZ mutation did not affect growth and development, but led to sterility in both males and females. Eupyrene sperm bundles of mutant males exhibited developmental defects, while the apyrene sperm bundles were normal, which were further confirmed through double copulation experiments with sex-lethal mutants, which males possess functional eupyrene sperm and abnormal apyrene sperm. In female mutant moths, ovarioles were severely degenerated and the eggs in ovarioles were deformed compared with that of wild type (WT). Further RNA-seq and RT-qPCR analysis revealed that amounts of piRNAs and transposon expression were dysregulated in gonads of mutants. In summary, this study has demonstrated vital roles of BmGASZ in gametogenesis through regulating the piRNA pathway in B. mori.

Repurposing the multiple sclerosis drug Siponimod for osteoporosis treatment.

Osteoporosis is the most common bone disorder, in which an imbalance between osteoclastic bone resorption and osteoblastic bone formation disrupts bone homeostasis. Osteoporosis management using anti-osteoclastic agents is a promising strategy; however, this remains an unmet need. Sphingosine-1-phosphate (S1P) and its receptors (S1PRs) are essential for maintaining bone homeostasis. Here, we identified that Siponimod, a Food and Drug Administration-approved S1PR antagonist for the treatment of multiple sclerosis, shows promising therapeutic effects against osteoporosis by inhibiting osteoclast formation and function. We found that Siponimod inhibited osteoclast formation in a dose-dependent manner without causing cytotoxicity. Podosome belt staining and bone resorption assays indicated that Siponimod treatment impaired osteoclast function. Western blot and qPCR assays demonstrated that Siponimod suppressed the expression of osteoclast-specific markers, including C-Fos, Nftac1, and Ctsk. Mechanistically, we validated that Siponimod downregulated receptor activator of nuclear factor kappa B ligand (RANKL)-induced Mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathways during osteoclastogenesis. Moreover, in a preclinical mouse model, Siponimod prevented ovariectomy-induced bone loss by suppressing osteoclast activity in vivo. Collectively, these results suggest that Siponimod could serve as an alternative therapeutic agent for the treatment of osteoporosis.

Earth-abundant Zn-dipyrrin chromophores for efficient CO2 photoreduction.

The development of strong sensitizing and Earth-abundant antenna molecules is highly desirable for CO2 reduction through artificial photosynthesis. Herein, a library of Zn-dipyrrin complexes (Z-1-Z-6) are rationally designed via precisely controlling their molecular configuration to optimize strong sensitizing Earth-abundant photosensitizers. Upon visible-light excitation, their special geometry enables intramolecular charge transfer to induce a charge-transfer state, which was first demonstrated to accept electrons from electron donors. The resulting long-lived reduced photosensitizer was confirmed to trigger consecutive intermolecular electron transfers for boosting CO2-to-CO conversion. Remarkably, the Earth-abundant catalytic system with Z-6 and Fe-catalyst exhibits outstanding performance with a turnover number of >20 000 and 29.7% quantum yield, representing excellent catalytic performance among the molecular catalytic systems and highly superior to that of noble-metal photosensitizer Ir(ppy)2(bpy)+ under similar conditions. Experimental and theoretical investigations comprehensively unveil the structure-activity relationship, opening up a new horizon for the development of Earth-abundant strong sensitizing chromophores for boosting artificial photosynthesis.

Three-dimensional cross-linked network deep eutectic gel polymer electrolyte with the self-healing ability enable by hydrogen bonds and dynamic disulfide bonds.

Solid polymer electrolytes (SPEs) are effective solutions for the development of high-performance and flexible lithium metal batteries (LMBs). However, the key problems of SPEs including low ionic conductivity and inability to repair damage have hindered their industrialization process. In this work, a three-dimensional (3D) cross-linked network gel polymer electrolyte (CNGPE) is designed. The addition of deep eutectic solvent (DES) improves the ionic conductivity of CNGPE. The hydrogen bonds and dynamic disulfide bonds in the 3D cross-linked network endow CNGPE rapid self-healing ability at ambient temperature. In addition, the addition of lithium difluoro(oxalato)borate (LiDFOB) and lithium nitrate (LiNO3) helps to form a stable solid electrolyte interface (SEI). Due to the ingenious design, the Li/CNGPE/Li symmetrical cell exhibits excellent interface stability and no short circuit occurs for more than 800 h. The assembled LiFePO4/CNGPE/Li cell exhibits a discharge specific capacity of 126 mAh g-1 after 960 cycles at 0.5C. This work has shown that the self-healing gel polymer electrolyte containing DES provides an effective and feasible method for the development of high-performance LMBs.

A novel entity of HIPK2::YAP1 pulmonary fibromatosis.

BACKGROUND: Pulmonary fibromatosis (PF) is a specific variant of fibromatosis, which is rarely reported occurring in the lung. PF with HIPK2-YAP1 fusion was a novel entity. CASE PRESENTATION: In this report, a 66-year-old male with PF had been smoking over 40 years. Multiple cords and small nodules in both lungs had been detected in a health examination two years earlier at our hospital. But approximately twofold enlarged in the lingual segment of the upper lobe in the left lung were disclosed in this year. Immunohistochemical analysis demonstrated that the vimentin and ß-Catenin were positive in the largest nodule. After underwent a DNA/RNA panel next-generation sequencing (NGS), missense mutations and HIPK2-YAP1 fusion were found in this sample. Ultimately, the case diagnosis as PF with HIPK2-YAP1 fusion after multidisciplinary treatment. Currently, the patient is doing well and recurrence-free at 14 months post-surgery. CONCLUSIONS: It's difficult for patients with complex morphology to make accurate diagnosis solely based on morphology and immunohistochemistry. But molecular detection is an effective method for further determining pathological subtypes.

Integrating predictive coding and a user-centric interface for enhanced auditing and quality in cancer registry data.

Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform. The embedded system offers a comprehensive view of patient reports annotated with significant registry concepts to facilitate the manual coding process and elevate overall quality. Extensive evaluations, including comparisons with state-of-the-art methods, were conducted using a lung cancer dataset comprising 1428 patients from the medical center. The experimental results illustrate the effectiveness of the developed system, consistently achieving F1-scores of 0.85 and 1.00 across 30 coding items. Registrar feedback highlights the system's reliability as a tool for assisting and auditing the abstraction. By presenting key registry items along the timeline of a patient's reports with accurate code predictions, the system improves the quality of registrar outcomes and reduces the labor resources and time required for data abstraction. Our study highlights advancements in cancer registry coding practices, demonstrating that the proposed hybrid weighted neural-symbolic cancer registry system is reliable and efficient for assisting cancer registrars in the coding workflow and contributing to clinical outcomes.

Assessment of Masseter Volume and Postoperative Stability After Orthognathic Surgery in Patients With Skeletal Class III Malocclusion With Facial Asymmetry.

OBJECTIVE: This study aimed to evaluate the effect of orthognathic surgery on masseter volume in patients with skeletal Class III malocclusion with facial asymmetry and the effect of masseter volume on stability in orthognathic surgery. METHODS: This research studied 16 patients with Class III malocclusion with facial asymmetry who received combined orthodontic-orthognathic treatment and underwent craniofacial computed tomography (CT) before (T0), 2 weeks after (T1), and 6 months after (T2) surgery. Three-dimensional (3D) CT images were retrospectively analyzed, using 3D volume reconstruction to obtain the masseter volume and examine the impact of the masseter volume on stability in orthognathic surgery. RESULTS: A statistically significant difference (P < 0.05) in the volume of the masseter was found up to 6 months after orthognathic surgery compared with the preoperative period, and the reduction in the masticatory muscle volume on the lengthened side is greater than on the shortened side (P < 0.05). The volume of both masseters differed according to facial asymmetry, and the difference was significantly reduced after orthognathic surgery (P < 0.05). During the period time (T1-T2), cephalometric maxillary marker points were not significantly different (P > 0.05), and mandibular marker points were significantly anteriorly shifted (P < 0.05). There was an association between the masseter volume and anterior shift of point B (R > 0.5, P < 0.05), the upward and anterior shifts of the gonion point differed between the lengthened and shortened sides (P < 0.05). CONCLUSION: The size of the masseter becomes smaller 6 months after orthognathic surgery, and orthognathic surgery improves both bone and soft tissue symmetry. A larger sagittal relapse of mandibular setback occurred in patients with greater masseter volume. Considering these alterations may be helpful in planning orthognathic surgery.

Enhancing the electrochemical properties of TiNb2O7 anodes with SP-CNT binary conductive agents for both liquid and solid state lithium ion batteries.

A high performance oxide composite electrode is obtained with a two-step solid state calcined titanium niobium oxide TiNb2O7 (TNO) anode and super P-carbon nanotube (SP-CNT) binary conductive agents. The solid state synthesized TNO-0.2C (the proportion of CNTs in the binary conductive agent is 20% wt) anode exhibits a high reversible discharge capacity of 278.6 mA h g-1 at 0.5C, a competitive rate capability with reported works that employed wet chemical methods at moderate rates (178.1 mA h g-1 at 10C), and an excellent capacity retention of 92.2% after 200 cycles at 1.5C/1.5C. The enhancement in electrochemical properties of the TNO-0.2C anode is mainly attributed to the combination of the short range and long range conductive agents in the SP-CNT binary conductive system, which guarantees an efficient electronic conductive network. The Li|Li1.3Al0.3Ti1.7(PO4)3 composite polymer electrolyte (LATPCPEs)|TNO-0.2C solid state batteries are also assembled, which deliver a high initial reversible discharge capacity of 241.3 mA h g-1 at 1C and a good capacity retention rate of 93% after 50 cycles. This work provides an efficient way to improve the electrochemical properties of TNO anodes in lithium ion batteries, especially for solid state batteries.

Antimicrobial resistance and population genomics of emerging multidrug-resistant Salmonella 4,[5],12:i:- in Guangdong, China.

Salmonella 4,[5],12:i:-, a monophasic variant of Salmonella Typhimurium, has emerged as a global cause of multidrug-resistant salmonellosis and has become endemic in many developing and developed countries, especially in China. Here, we have sequenced 352 clinical isolates in Guangdong, China, during 2009-2019 and performed a large-scale collection of Salmonella 4,[5],12:i:- with whole genome sequencing (WGS) data across the globe, to better understand the population structure, antimicrobial resistance (AMR) genomic characterization, and transmission routes of Salmonella 4,[5],12:i:- across Guangdong. Salmonella 4,[5],12:i:- strains showed broad genetic diversity; Guangdong isolates were found to be widely distributed among the global lineages. Of note, we identified the formation of a novel Guangdong clade (Bayesian analysis of population structure lineage 1 [BAPS1]) genetically diversified from the global isolates and likely emerged around 1990s. BAPS1 exhibits unique genomic features, including large pan-genome, decreased ciprofloxacin susceptibility due to mutation in gyrA and carriage of plasmid-mediated quinolone resistance (PMQR) genes, and the multidrug-resistant IncHI2 plasmid. Furthermore, high genetic similarity was found between strains collected from Guangdong, Europe, and North America, indicating the association with multiple introductions from overseas. These results suggested that global dissemination and local clonal expansion simultaneously occurred in Guangdong, China, and horizontally acquired resistance to first-line and last-line antimicrobials at local level, underlying emergences of extensive drug and pan-drug resistance. Our findings have increased the knowledge of global and local epidemics of Salmonella 4,[5],12:i:- in Guangdong, China, and provided a comprehensive baseline data set essential for future molecular surveillance.IMPORTANCESalmonella 4,[5],12:i:- has been regarded as the predominant pandemic serotype causing diarrheal diseases globally, while multidrug resistance (MDR) constitutes great public health concerns. This study provided a detailed and comprehensive genome-scale analysis of this important Salmonella serovar in the past decade in Guangdong, China. Our results revealed the complexity of two distinct transmission modes, namely global transmission and local expansion, circulating in Guangdong over a decade. Using phylogeography models, the origin of Salmonella 4,[5],12:i:- was predicted from two aspects, year and country, that is, Salmonella 4,[5],12:i:- emerged in 1983, and was introduced from the UK, and subsequently differentiated into the local endemic lineage circa 1991. Additionally, based on the pan-genome analysis, it was found that the gene accumulation rate in local endemic BAPS 1 lineage was higher than in other lineages, and the horizontal transmission of MDR IncHI2 plasmid associated with high resistance played a major role, which showed the potential threat to public health.

Longitudinal Extension of Double π-Helix Enables Near-Infrared Amplified Dissymmetry and Chiroptical Response.

Near-infrared (NIR) circularly polarized light absorbing or emitting holds great promise for highly sensitive and precise bioimaging, biosensing, and photodetectors. Aiming at designing NIR chiral molecular systems with amplified dissymmetry and robust chiroptical response, herein, we present a series of double π-helical dimers with longitudinally extended π-entwined substructures via Ullmann or Yamamoto homocoupling reactions. Circular dichroism (CD) spectra revealed an approximate linear bathochromic shift with the rising number of naphthalene subunits, indicating a red to NIR chiroptical response. Particularly, the terrylene diimide-entwined dimers exhibited the strongest CD intensities, with the maximal |Δε| reaching up to 393 M-1 cm-1 at 666 nm for th-TDI[2]; and a record-high chiroptical response (|ΔΔε|) between the neutral and dianionic species of 520 M-1 cm-1 at 833 nm for th-TDI[2]Cl was achieved upon further reduction to its dianionic state. Time-dependent density functional theory (TDDFT) calculations suggested that the pronounced intensification of the CD spectra originated from a simultaneous enhancement of both electric (µ) and magnetic (m) transition dipole moments, ultimately leading to an overall increase in the rotatory strength (R). Notably, the circularly polarized luminescence (CPL) brightness (BCPL) reached 77 M-1 cm-1 for th-TDI[2]Cl, among the highest values reported for NIR-CPL emitters. Furthermore, all chiral dianions exhibited excellent air stability under ambient conditions with half-life times of up to 10 days in N-methylpyrrolidone (NMP), which is significant for future biological applications and chiroptic switches.

Establishing subdivisions of M1 stage nasopharyngeal carcinoma based on decision tree classification: A multicenter retrospective study.

OBJECTIVES: To meet the demand for personalized treatment, effective stratification of patients with metastatic nasopharyngeal carcinoma (mNPC) is essential. Hence, our study aimed to establish an M1 subdivision for prognostic prediction and treatment planning in patients with mNPC. MATERIALS AND METHODS: This study included 1239 patients with mNPC from three medical centers divided into the synchronous mNPC cohort (smNPC, n = 556) to establish an M1 stage subdivision and the metachronous mNPC cohort (mmNPC, n = 683) to validate this subdivision. The primary endpoint was overall survival. Univariate and multivariate Cox analyses identified covariates for the decision-tree model, proposing an M1 subdivision. Model performance was evaluated using time-dependent receiver operating characteristic curves, Harrell's concordance index, calibration plots, and decision curve analyses. RESULTS: The proposed M1 subdivisions were M1a (≤5 metastatic lesions), M1b (>5 metastatic lesions + absent liver metastases), and M1c (>5 metastatic lesions + existing liver metastases) with median OS of 34, 22, and 13 months, respectively (p < 0.001). This M1 subdivision demonstrated superior discrimination (C-index = 0.698; 3-year AUC = 0.707) and clinical utility over those of existing staging systems. Calibration curves exhibited satisfactory agreement between predictions and actual observations. Internal and mmNPC cohort validation confirmed the robustness. Survival benefits from local metastatic treatment were observed in M1a, while immunotherapy improved survival in patients with M1b and M1c disease. CONCLUSION: This novel M1 staging strategy provides a refined approach for prognostic prediction and treatment planning in patients with mNPC, emphasizing the potential benefits of local and immunotherapeutic interventions based on individualized risk stratification.

Corrigendum: Tpr deficiency disrupts erythroid maturation with impaired chromatin condensation in zebrafish embryogenesis.

[This corrects the article DOI: 10.3389/fcell.2021.709923.].

Recent Progress of Low-Dimensional Metal-Organic Frameworks for Aqueous Zinc-Based Batteries.

Aqueous zinc-based batteries (AZBs) are promising energy storage solutions with remarkable safety, abundant Zn reserve, cost-effectiveness, and relatively high energy density. However, AZBs still face challenges such as anode dendrite formation that reduces cycling stability and limited cathode capacity. Recently, low-dimensional metal-organic frameworks (LD MOFs) and their derivatives have emerged as promising candidates for improving the electrochemical performance of AZBs owing to their unique morphologies, high structure tunability, high surface areas, and high porosity. However, clear guidelines for developing LD MOF-based materials for high-performance AZBs are scarce. In this review, the recent progress of LD MOF-based materials for AZBs is critically examined. The typical synthesis methods and structural design strategies for improving the electrochemical performance of LD MOF-based materials for AZBs are first introduced. The recent noteworthy research achievements are systematically discussed and categorized based on their applications in different AZB components, including cathodes, anodes, separators, and electrolytes. Finally, the limitations are addressed and the future perspectives are outlined for LD MOFs and their derivatives in AZB applications. This review provides clear guidance for designing high-performance LD MOF-based materials for advanced AZBs.

Bone morphogenetic protein 4 derived from the cerebrospinal fluid in patients with postherpetic neuralgia induces allodynia via the crosstalk between microglia and astrocyte.

INTRODUCTION: During postherpetic neuralgia (PHN), the cerebral spinal fluid (CSF) possesses the capability to trigger glial activation and inflammation, yet the specific changes in its composition remain unclear. Recent findings from our research indicate elevations of central bone morphogenetic protein 4 (BMP4) during neuropathic pain (NP), serving as an independent modulator of glial cells. Herein, the aim of the present study is to test the CSF-BMP4 expressions and its role in the glial modulation in the process of PHN. METHODS: CSF samples were collected from both PHN patients and non-painful individuals (Control) to assess BMP4 and its antagonist Noggin levels. Besides, intrathecal administration of both CSF types was conducted in normal rats to evaluate the impact on pain behavior, glial activity, and inflammation.; Additionally, both Noggin and STAT3 antagonist-Stattic were employed to treat the PHN-CSF or exogenous BMP4 challenged cultured astrocytes to explore downstream signals. Finally, microglial depletion was performed prior to the PHN-CSF intervention so as to elucidate the microglia-astrocyte crosstalk. RESULTS: BMP4 levels were significantly higher in PHN-CSF compared to Control-CSF (P < 0.001), with a positive correlation with pain duration (P < 0.05, r = 0.502). Comparing with the Control-CSF producing moderate paw withdrawal threshold (PWT) decline and microglial activation, PHN-CSF further exacerbated allodynia and triggered both microglial and astrocytic activation (P < 0.05). Moreover, PHN-CSF rather than Control-CSF evoked microglial proliferation and pro-inflammatory transformation, reinforced iron storage, and activated astrocytes possibly through both SMAD159 and STAT3 signaling, which were all mitigated by the Noggin application (P < 0.05). Next, both Noggin and Stattic effectively attenuated BMP4-induced GFAP and IL-6 upregulation, as well as SMAD159 and STAT3 phosphorylation in the cultured astrocytes (P < 0.05). Finally, microglial depletion diminished PHN-CSF induced astrogliosis, inflammation and endogenous BMP4 expression (P < 0.05). CONCLUSION: Our study highlights the role of CSF-BMP4 elevation in glial activation and allodynia during PHN, suggesting a potential therapeutic avenue for future exploration.

Superconducting Two-Dimensional FeSe Grown on the Fe-Enriched Interface.

Two-dimensional (2D) tetragonal FeSe has sparked extensive research interest owing to its tunable superconductivity, providing valuable insights into the design of high-temperature superconductors. Currently, the intricate Fe-Se phase diagram poses a challenge to the controlled synthesis of superconducting 2D FeSe in a pure tetragonal phase. Here, we exploit the ion-exchange property of fluorophlogopite mica to devise a straightforward approach for the phase-controlled synthesis of tetragonal FeSe on an Fe-enriched mica surface within a molten salt environment. This method successfully produces highly crystalline FeSe in a pure tetragonal phase with adjustable thickness. We investigated the surface composition of the postgrowth mica substrate using various microscopic and spectroscopic characterizations to highlight the importance of the Fe-enriched growth interface in the phase-selective synthesis of 2D tetragonal FeSe. The obtained 2D FeSe exhibited 2D superconductivity, comparable to that of FeSe mechanically exfoliated from bulk crystals, confirming the high quality of our samples. Beyond tetragonal FeSe, 2D antiferromagnetic FeTe and superconducting FeSxSeyTe1-x-y have been phase-selectively synthesized via this approach. Our study elucidates the significance of the growth interface on the phase-selective synthesis of 2D materials and presents potential opportunities for the phase-controlled synthesis of 2D multiphase materials via the rational design of the growth interface.

Buffer Chain Model for Understanding Crystallization Competition in Conjugated Polymers.

It remains challenging to comprehensively understand the packing models of conjugated polymers, in which side chains play extremely critical roles. The side chains are typically flexible and non-conductive and are widely used to improve the polymer solubility in organic solutions. Herein, a buffer chain model is proposed to describe link between conjugated backbone and side chains for understanding the relationship of crystallization competition of conductive conjugated backbones and non-conductive side chains. A longer buffer chain is beneficial for alleviating such crystallization competition and further promoting the spontaneous packing of conjugated backbones, resulting in enhanced charge transport properties. Our results provide a novel concept for designing conjugated polymers towards ordered organization and enhanced electronic properties and highlight the importance of balancing the competitive interactions between different parts of conjugated polymers.

Konjac glucomannan films incorporated pectin-stabilized Mandarin oil emulsions: Structure, properties, and application in fruit preservation.

To enhance the water-resistance and antibacterial properties of KGM films, mandarin oil (MO), was directly emulsified by pectin and then dispersed to the KGM matrix. The effect of MO concentration (0, 0.5, 1.0, 1.5, and 2 wt%) on the performance of the film-forming emulsions as well as the emulsion films was investigated. The results revealed that pectin could encapsulate and protect MO, and KGM as film matrix could further contributed to the high stability of the film-forming emulsions. The FT-IR, XRD, and SEM suggested that MO stabilized by pectin was uniformly distributed in the KGM matrix. The compatibility and good interaction between KGM and pectin contributed to highly dense and compact structure. Furthermore, increasing the concentration of MO effectively improved water-resistance, oxygen barrier, and antimicrobial activity of the KGM based films. The 1.5 wt% MO loaded KGM film had the highest tensile strength (72.22 MPa) and water contact angle (θ = 95.73°), reduced the WVP and oxygen permeability by about 25.8 % and 32.8 times, respectively, prolonged the shelf life of strawberries for 8 days. As demonstrated, the 1.5 wt% MO-loaded KGM film has considerable potential for high-performance natural biodegradable active films to ensure food safety and reduce environmental impacts.

Mechanosensitive protein polycystin-1 promotes periosteal stem/progenitor cells osteochondral differentiation in fracture healing.

Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin (Ctsk)-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk+ PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk+ PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion.