From Short Circuit to Completed Circuit: Conductive Hydrogel Facilitating Oral Wound Healing.

The primary challenges posed by oral mucosal diseases are their high incidence and the difficulty in managing symptoms. Inspired by the ability of bioelectricity to activate cells, accelerate metabolism, and enhance immunity, a conductive polyacrylamide/sodium alginate crosslinked hydrogel composite containing reduced graphene oxide (PAA-SA@rGO) is developed. This composite possesses antibacterial, anti-inflammatory, and antioxidant properties, serving as a bridge to turn the "short circuit" of the injured site into a "completed circuit," thereby prompting fibroblasts in proximity to the wound site to secrete growth factors and expedite tissue regeneration. Simultaneously, the PAA-SA@rGO hydrogel effectively seals wounds to form a barrier, exhibits antibacterial and anti-inflammatory properties, and prevents foreign bacterial invasion. As the electric field of the wound is rebuilt and repaired by the PAA-SA@rGO hydrogel, a 5 × 5 mm2 wound in the full-thickness buccal mucosa of rats can be expeditiously mended within mere 7 days. The theoretical calculations indicate that the PAA-SA@rGO hydrogel can aggregate and express SOX2, PITX1, and PITX2 at the wound site, which has a promoting effect on rapid wound healing. Importantly, this PAA-SA@rGO hydrogel has a fast curative effect and only needs to be applied for the first three days, which significantly improves patient satisfaction during treatment.

Carbon Quantum Dots for Long-Term Protection against UV Degradation and Acidification in Paper-Based Relics.

Paper-based cultural relics constitute a significant and invaluable part of human civilization and cultural heritage. However, they are highly vulnerable to environmental factors such as ultraviolet (UV) photodegradation and acidification degradation, posing substantial threats to their long-term preservation. Carbon quantum dots (CQDs), known for their outstanding optical properties, high water solubility, and good safety, offer a promising solution for slowing down UV damage and acidification of paper-based relics during storage and transportation. Herein, we propose a feasible strategy for the simple preparation of CQDs with high dispersion stability, excellent UV absorption, room-temperature phosphorescence, and photostability for the safety protection of paper. Accelerated aging experiments were conducted using UV and dry-heat aging methods on both CQD-protected paper and unprotected paper, respectively, to evaluate the effectiveness of CQD protection. The results demonstrate a slowdown in both the oxidation and acid degradation processes of the protected paper under both UV-aging and dry-heat aging conditions. Notably, CQDs with complex luminescence patterns of both fluorescence and room-temperature phosphorescence also endue them as enhanced optical anticounterfeiting materials for multifunctional paper protection. This research provides a new direction for the protection of paper-based relics with emerging carbon nanomaterials.

Regulating Phase Distribution of Dion-Jacobson Perovskite Colloidal Multiple Quantum Wells Toward Highly Stable Deep-Blue Emission.

Metal halide perovskite colloidal quantum wells (CQWs) hold great promise for modern photonics and optoelectronics. However, current studies focus on Ruddlesden-Popper (R-P) phase perovskite CQWs that contain bilayers of monovalent long-chain alkylamomoniums between the separated perovskite octahedra layers. The bilayers are packed back-to-back via weak van der Waals interaction, resulting in inferior charge carrier transport and easier decomposition of perovskite. This report first creates a new type of perovskite colloidal multiple QWs (CMQWs) in the form of Dion-Jacobson (D-J) structure by introducing an asymmetric diammonium cation. Furthermore, the phase distribution is optimized by the synergistic effect of valeric acid and zwitterionic lecithin, finally achieving pure deep-blue emission at 435 nm with narrow full width at half maximum. The diammonium layer in D-J perovskite CMQWs features extremely short width of only ≈0.6 nm, thereby contributing to more effective charge carrier transport and higher stability. Through the continuous photoluminescence (PL) measurement and corresponding theoretical calculation, the higher stability of D-J perovskite CMQWs than that of R-P structural CMQWs is confirmed. This work reveals the inherent superior stability of D-J structural CMQWs, which opens a new direction for fabricating stable perovskite optoelectronics.

Integrated reconstructive spectrometer with programmable photonic circuits.

Optical spectroscopic sensors are a powerful tool to reveal light-matter interactions in many fields. Miniaturizing the currently bulky spectrometers has become imperative for the wide range of applications that demand in situ or even in vitro characterization systems, a field that is growing rapidly. In this paper, we propose a novel integrated reconstructive spectrometer with programmable photonic circuits by simply using a few engineered MZI elements. This design effectively creates an exponentially scalable number of uncorrelated sampling channels over an ultra-broad bandwidth without incurring additional hardware costs, enabling ultra-high resolution down to single-digit picometers. Experimentally, we implement an on-chip spectrometer with a 6-stage cascaded MZI structure and demonstrate <10 pm resolution with >200 nm bandwidth using only 729 sampling channels. This achieves a bandwidth-to-resolution ratio of over 20,000, which is, to our best knowledge, about one order of magnitude greater than any reported miniaturized spectrometers to date.

Mapping the Identity of Transition Metal Doping and Surface Passivation in Indium Phosphide with Theoretical Calculation.

Understanding the electronic structure of doped InP quantum dots (QDs) is essential to optimize the material for specific optoelectronic applications. However, current synthesis approaches are often tedious and unfavorable for rational tunning. Herein, a combination of experimental and computational studies was conducted to address the doping mechanism and surface passivation of InP QDs. The successful dopant introduction requires low Cu doping concentration and heavy Mn doping, while the Ag doping amount is relatively moderate. This may correspond to the theoretical doping formation energy presented as Cu (-2.52 eV) < Ag (-1.76 eV) < Mn (-0.38 eV). As for surface passivation, inorganic ions and shell-like ZnS are unraveled through simulational investigation. Chloride ion promotes oriented growth toward tetrahedron morphology while nitrate-passivated InP QDs exhibit blurry transmission electron microscope (TEM) morphology. Correspondingly, the binding energy of chloride ion with (111) facet is -2.13 eV significantly lower than those of (110) and (100) facets. Further, the additional Zn 3d bands are more involved in the formation of conduction band, which optimized the Mn-doped InP with a 0.32 eV bandgap. These experimental and model results provide more microscopic details of doped InP, which can motivate theoretically exact control of guest ion stoichiometry with optimized characteristics for electrical devices.

Safety, tolerability, pharmacokinetics and efficacy of HB0017, a humanized monoclonal antibody that targets interleukin-17A, in healthy participants and patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Several interleukin (IL)-17 inhibitors have been approved for the treatment of moderate-to-severe plaque psoriasis (PsO). There is still scope for the development of affordable treatments for PsO. OBJECTIVES: To assess, in a phase Ia study, the safety, tolerability and pharmacokinetics (PK) of HB0017, a humanized monoclonal antibody that targets IL-17A, in healthy participants and patients with moderate-to-severe plaque PsO; and, in a phase Ib study, to assess the efficacy of HB0017 in patients with moderate-to-severe plaque PsO. METHODS: The phase Ia study (NCT04505033) was a randomized double-blind placebo-controlled dose-escalation study in healthy participants. Each cohort of 10 volunteers was randomly assigned to receive either a single dose of HB0017 (50 mg, 150 mg, 300 mg or 450 mg) or the matching placebo at a ratio of 4 : 1. The phase Ib study (NCT05442788) was a randomized double-blind placebo-controlled dose-escalation study in enrolled patients with moderate-to-severe plaque PsO. Each cohort of 10 patients was randomly assigned to receive either multiple doses of HB0017 (150 mg, 300 mg or 450 mg) or the matching placebo at a ratio of 4 : 1. RESULTS: HB0017 demonstrated dose-proportional linear PK and was tolerated across the dose range assessed. In the phase Ia and Ib studies, participants in both the HB0017 and placebo groups experienced treatment-emergent adverse events (69% vs. 87%, 96% vs. 100%, respectively). HB0017 demonstrated clinically meaningful effects in patients with moderate-to-severe plaque PsO. PASI 75 [≥ 75% improvement in Psoriasis Area and Severity Index (PASI)], PASI 90 (≥ 90% improvement in PASI) and static Physician Global Assessment (sPGA) 0/1 (i.e. 'clear' or 'almost clear') responses were 100% for the HB0017 300-mg group, with maximal improvements (100% or near 100% reductions from baseline) in PASI score observed at week 12, while the duration of effect was evident up to week 20. There was no clinical response in any participant in the placebo group in the phase Ib study. CONCLUSIONS: Overall, HB0017 showed acceptable safety and tolerability in both healthy participants and patients with moderate-to-severe plaque PsO. An encouraging signal of efficacy with a longer half-life provides HB0017 with the potential to be added to the currently available range of biologics targeting IL-17A.

Melatonin regulates cancer migration and stemness and enhances the anti-tumour effect of cisplatin.

Melatonin, a lipophilic hormone released from the pineal gland, has oncostatic effects on various types of cancers. However, its cancer treatment potential needs to be improved by deciphering its corresponding mechanisms of action and optimising therapeutic strategy. In the present study, melatonin inhibited gastric cancer cell migration and soft agar colony formation. Magnetic-activated cell sorting was applied to isolate CD133+ cancer stem cells. Gene expression analysis showed that melatonin lowered the upregulation of LC3-II expression in CD133+ cells compared to CD133- cells. Several long non-coding RNAs and many components in the canonical Wnt signalling pathway were altered in melatonin-treated cells. In addition, knockdown of long non-coding RNA H19 enhanced the expression of pro-apoptotic genes, Bax and Bak, induced by melatonin treatment. Combinatorial treatment with melatonin and cisplatin was investigated to improve the applicability of melatonin as an anticancer therapy. Combinatorial treatment increased the apoptosis rate and induced G0/G1 cell cycle arrest. Melatonin can regulate migration and stemness in gastric cancer cells by modifying many signalling pathways. Combinatorial treatment with melatonin and cisplatin has the potential to improve the therapeutic efficacy of both.

A Strategy Inspired by the Cicada Shedding Its Skin for Synthesizing the Natural Material NaFe3 S5 ·2H2 O.

Sulfide minerals hold significant importance in both fundamental science and industrial advancement. However, certain natural sulfide minerals, such as NaFe3 S5 ·2H2 O (NFS), pose great challenges for exploitation and synthesis due to their high susceptibility to oxidation. To date, no successful precedent exists for synthesizing NFS. Here, a novel approach to synthesizing low-cost and pollution-free NFS with high stability using the high-pressure hydrothermal method based solely on knowledge of its chemical formula is presented. Moreover, an innovative strategy inspired by the cicada's molting process to develop unstable natural materials is proposed. The mechanical, thermal, optical, electrochemical, and magnetic properties of the NFS are thoroughly investigated. The storage of lithium, sodium, and potassium ions is primarily concentrated in the gap between (0 0 1) crystal planes. Additionally, as a catalyst for hydrogen evolution reaction (HER) at 10 mA cm-2 , micron-sized NFS exhibits an excellent overpotential of 6.5 mV at 90 °C, surpassing those of reported HER catalysts of similar size. This research bridges the gap in the sulfide mineral family, overcomes limitations of the high-pressure hydrothermal method, and paves the way for future synthesis of natural minerals, lunar minerals, and Martian minerals.

Genome-wide characterization, phylogenetic and expression analysis of ABCG gene subfamily in cucumber (Cucumis sativus L.).

The ABCG is the largest subfamily of the ABC family with extensive functions, and only a few members have been identified in detail. However, more and more studies have shown that the members of this family are very important and are involved in many life processes such as plant development and response to various stresses. Cucumber is an important vegetable crops around the world. The cucumber development is essential for its production and quality. Meanwhile, various stresses have caused serious losses of cucumber. However, the ABCG genes were not well characterized and functioned in cucumber. In this study, the cucumber CsABCG gene family were identified and characterized, and their evolutionary relationship and functions were analyzed. The cis-acting elements and expression analysis showed that they played important role in development and responding to various biotic and abiotic stresses in cucumber. Phylogenetic analysis, sequence alignment and MEME (Multiple Em for Motif Elicitation) analysis indicated that the functions of ABCG proteins in different plants are evolutionarily conserved. Collinear analysis revealed that the ABCG gene family was highly conserved during the evolution. In addition, the potential binding sites of the CsABCG genes targeted by miRNA were predicted. These results will lay a foundation for further research on the function of the CsABCG genes in cucumber.

Advanced Composites Inspired by Biological Structures and Functions in Nature: Architecture Design, Strengthening Mechanisms, and Mechanical-Functional Responses.

The natural design and coupling of biological structures are the root of realizing the high strength, toughness, and unique functional properties of biomaterials. Advanced architecture design is applied to many materials, including metal materials, inorganic nonmetallic materials, polymer materials, and so on. To improve the performance of advanced materials, the designed architecture can be enhanced by bionics of biological structure, optimization of structural parameters, and coupling of multiple types of structures. Herein, the progress of structural materials is reviewed, the strengthening mechanisms of different types of structures are highlighted, and the impact of architecture design on the performance of advanced materials is discussed. Architecture design can improve the properties of materials at the micro level, such as mechanical, electrical, and thermal conductivity. The synergistic effect of structure makes traditional materials move toward advanced functional materials, thus enriching the macroproperties of materials. Finally, the challenges and opportunities of structural innovation of advanced materials in improving material properties are discussed.

A quantitative map of nuclear pore assembly reveals two distinct mechanisms.

Understanding how the nuclear pore complex (NPC) is assembled is of fundamental importance to grasp the mechanisms behind its essential function and understand its role during the evolution of eukaryotes1-4. There are at least two NPC assembly pathways-one during the exit from mitosis and one during nuclear growth in interphase-but we currently lack a quantitative map of these events. Here we use fluorescence correlation spectroscopy calibrated live imaging of endogenously fluorescently tagged nucleoporins to map the changes in the composition and stoichiometry of seven major modules of the human NPC during its assembly in single dividing cells. This systematic quantitative map reveals that the two assembly pathways have distinct molecular mechanisms, in which the order of addition of two large structural components, the central ring complex and nuclear filaments are inverted. The dynamic stoichiometry data was integrated to create a spatiotemporal model of the NPC assembly pathway and predict the structures of postmitotic NPC assembly intermediates.

Efficacy, Safety and Pharmacokinetics of IL-17 Monoclonal Antibody Injection (AK111) in Patients with Moderate-to-Severe Plaque Psoriasis: A Randomized, Double-Blinded, Placebo-Controlled Phase Ib Multidose Escalation Clinical Study.

OBJECTIVES: To evaluate the safety, tolerability, immunogenicity, and induced expression of skin biomarkers of AK111 injection after multiple administrations in subjects with moderate-to-severe plaque psoriasis. METHODS: This study is a randomized, double-blinded, placebo-parallel-controlled study using a dose escalation mode of multiple doses. A total of 48 subjects were sequentially randomized to receive each AK111 dose regimen (75 mg, 150 mg, 300 mg, 450 mg) or the corresponding placebo. All subjects were treated with the study drug at weeks 0, 1, 4, and 8 and were unblinded at week 12, with the placebo group ending and the AK111 group being followed up to 20 weeks. RESULTS: At week 12, compared with placebo, the percentage of subjects achieving Psoriasis Area and Severity Index 75 (PASI75) and static Physician Global Assessment (sPGA) 0/1 in the AK111 75 mg-450 mg dose groups was significantly increased, and higher PASI90 was achieved in the 150 mg, 300 mg, and 450 mg dose groups than in the 75 mg group. All efficacy indicators were maintained at week 20. The incidence of treatment-emergent anti-drug antibodies (ADAs) was 0% (0/48). Neutralizing antibodies (NAbs) were not detected in any subject. The proportion of subjects who reported any treatment-emergent adverse event (TEAE) was 75.0% in the AK111 group, similar to the 66.7% in the placebo group. The most commonly reported adverse events were hyperglycemia, elevated blood pressure, and hypokalemia. The AK111 pharmacokinetics showed approximate dose proportionality with regard to the maximum observed concentration (Cmax) and area under the curve from 0 to the time of the last quantifiable concentration (AUC0-t) following subcutaneous injection doses of 150-450 mg. CONCLUSIONS: After moderate-to-severe plaque psoriasis subjects received multiple subcutaneous AK111 injections of 150-450 mg, AK111 exposure increased in a roughly dose-proportional relationship. AK111 was safe and tolerable. In subjects with moderate-to-severe plaque psoriasis, AK111 demonstrated encouraging preliminary efficacy, which was sustained for a relatively long time after the last dose administration. CLINICAL TRIAL REGISTRATION: The clinical trial identification number is NCT05504317.

Influences of different surface oxygen species on oxidation of toluene and/or benzene and their reaction pathways over Cu-Mn metal oxides.

Catalytic oxidation is considered as the most effective and economical method to remove low concentration volatile organic compounds (VOCs). Activation of oxygen to form active oxygen species on metal oxides catalyst plays a key role in the process. Three copper-manganese oxide catalysts with cubic Cu1.5Mn1.5O4 phases were prepared by microwave heating (CM-MW), sol-gel (CM-SG) and co-precipitation (CM-CP) methods, and applied for the elimination of toluene and benzene as representative aromatic VOCs. These catalysts exhibit different catalytic oxidation performance due to their different physicochemical properties. Various characterizations were used to clarify the role of different oxygen species in the oxidation of VOCs, and the reaction pathway. In situ DRIFTS were carried out to explore the function of surface adsorbed oxygen, oxygen vacancy, and surface lattice oxygen in the catalytic oxidation of VOCs over three catalysts. Various types of intermediate species and detailed reaction pathways are also explored by combining in situ DRIFTS and mass spectrometry. Among these catalysts, CM-MW with nanosheet morphology shows the best catalytic oxidation performance of toluene and/or benzene with/without H2O due to the most abundant active oxygen species, and the highest oxygen vacancy concentration which is beneficial to activate oxygen. Meanwhile, toluene and benzene do not interfere with each other during the mixture oxidation. This study can provide new inspiration for rational design of metal oxide catalysts to remove VOCs.

Remodeling tumor microenvironment with natural products to overcome drug resistance.

With cancer incidence rates continuing to increase and occurrence of resistance in drug treatment, there is a pressing demand to find safer and more effective anticancer strategy for cancer patients. Natural products, have the advantage of low toxicity and multiple action targets, are always used in the treatment of cancer prevention in early stage and cancer supplement in late stage. Tumor microenvironment is necessary for cancer cells to survive and progression, and immune activation is a vital means for the tumor microenvironment to eliminate cancer cells. A number of studies have found that various natural products could target and regulate immune cells such as T cells, macrophages, mast cells as well as inflammatory cytokines in the tumor microenvironment. Natural products tuning the tumor microenvironment via various mechanisms to activate the immune response have immeasurable potential for cancer immunotherapy. In this review, it highlights the research findings related to natural products regulating immune responses against cancer, especially reveals the possibility of utilizing natural products to remodel the tumor microenvironment to overcome drug resistance.

Facile synthesis of red-emissive carbon dots with theoretical understanding for cellular imaging.

Recently, red emissive carbon dots (R-CDs) have drawn widespread attention on account of their desirable fluorescence properties and good biocompatibility. Despite great efforts, facile synthesis of R-CDs for cellular imaging remains challenging and the fluorescence mechanism of R-CDs is still elusive. Herein, p-phenylenediamine-derived R-CDs with excitation-independency were successfully obtained through a facile solvothermal approach together with proportional precipitation. The fluorescent solvatochromism of R-CDs is realized, while high polarity leads to higher degree of dipole interaction between R-CDs and different solvents, favoring for emissive red-shift. Furthermore, density functional theory is adopted to explore the optical and electronic characteristics of some polycyclic aromatic molecules. Among different configurations, pyridine nitrogen and carbonyl bonds could relatively increase the charge density and significantly narrow the band gap, which can provide a crucial theoretical basis for the precise preparation of R-CDs. Moreover, R-CDs possess favorable cellular imaging ability, which indicates their potential for a promising candidate as fluorescence probes in bioimaging.

Genome-Wide Identification and Characterization of the CC-NBS-LRR Gene Family in Cucumber (Cucumis sativus L.).

The NBS-LRR (NLR) gene family plays a pivotal role in regulating disease defense response in plants. Cucumber is one of the most important vegetable crops in the world, and various plant diseases, including powdery mildew (PM), cause severe losses in both cucumber productivity and quality annually. To characterize and understand the role of the CC-NBS-LRR(CNL) family of genes in disease defense response in cucumber plants, we performed bioinformatical analysis to characterize these genes systematically. We identified 33 members of the CNL gene family in cucumber plants, and they are distributed on each chromosome with chromosome 4 harboring the largest cluster of five different genes. The corresponding CNL family member varies in the number of amino acids and exons, molecular weight, theoretical isoelectric point (pI) and subcellular localization. Cis-acting element analysis of the CNL genes reveals the presence of multiple phytohormone, abiotic and biotic responsive elements in their promoters, suggesting that these genes might be responsive to plant hormones and stress. Phylogenetic and synteny analysis indicated that the CNL proteins are conserved evolutionarily in different plant species, and they can be divided into four subfamilies based on their conserved domains. MEME analysis and multiple sequence alignment showed that conserved motifs exist in the sequence of CNLs. Further DNA sequence analysis suggests that CsCNL genes might be subject to the regulation of different miRNAs upon PM infection. By mining available RNA-seq data followed by real-time quantitative PCR (qRT-PCR) analysis, we characterized expression patterns of the CNL genes, and found that those genes exhibit a temporospatial expression pattern, and their expression is also responsive to PM infection, ethylene, salicylic acid, and methyl jasmonate treatment in cucumber plants. Finally, the CNL genes targeted by miRNAs were predicted in cucumber plants. Our results in this study provided some basic information for further study of the functions of the CNL gene family in cucumber plants.

Endogenous health risks, poverty traps, and the roles of health insurance in poverty alleviation.

BACKGROUND: Family education investment is a key factor in reducing intergenerational transmission of poverty. At the price of higher health risk, the poor may overdraw their bodies to earn more money to invest in education. This study investigates the effect of physical overdraft, health risks and health insurance on poverty and economic growth. METHODS: This paper proposes an economic development model of endogenous health risks and poverty by setting up a physical overdraft decision. Furthermore, we introduce mutual health insurance mechanism to analyze its poverty alleviation effects. RESULTS: First, this study shows that health risks weaken the economy and are among the leading causes of poverty. Second, mutual health insurance can alleviate, but not completely eliminate, the negative impact of health risks on the economy. Third, appropriate health insurance arrangements can lift some or even all poor households out of poverty. CONCLUSION: Health risks have a significant effect on poverty. Furthermore, health insurance mechanisms have the advantages of transferring health risks, reducing poverty and improving health equity.

Synergistic Effect of Halogen Ions and Shelling Temperature on Anion Exchange Induced Interfacial Restructuring for Highly Efficient Blue Emissive InP/ZnS Quantum Dots.

InP quantum dots (QDs) have attracted much attention owing to their nontoxic properties and shown great potential in optoelectronic applications. Due to the surface defects and lattice mismatch, the interfacial structure of InP/ZnS QDs plays a significant role in their performance. Herein, the formation of In-S and Sx -In-P1-x interlayers through anion exchange at the shell-growth stage is revealed. More importantly, it is proposed that the composition of interface is dependent on the synergistic effect of halogen ions and shelling temperature. High shelling temperature contributes to the optical performance improvement resulting from the formation of interlayers, besides the thicker ZnS shell. Moreover, the effect relates to the halogen ions where I- presents more obvious enhancement than Br- and Cl- , owing to their different ability to coordinate with In dangling bonds, which are inclined to form In-S and Sx -In-P1-x bonds. Further, the anion exchange under I- -rich environment causes a blue-shift of emission wavelength with shelling temperature increasing, unobserved in a Cl- - or Br- -rich environment. It contributes to the preparation of highly efficient blue emissive InP/ZnS QDs with emission wavelength of 473 nm, photoluminescence quantum yield of ≈50% and full width at half maximum of 47 nm.

Simple Structural Descriptor Obtained from Symbolic Classification for Predicting the Oxygen Vacancy Defect Formation of Perovskites.

Symbolic classification is an approach of interpretable machine learning for building mathematical formulas that fit certain data sets. In this work, symbolic classification is used to establish the relationship between oxygen vacancy defect formation energy and structural features. We find a structural descriptor na(ra/Ena - rb), where na is the valence of the a-site ion, ra is the radius of the a-site ion, Ena is the electronegativity of the a-site ion, and rb is the radius of the b-site ion. It accelerates the screening of defect-free oxide perovskites in advance of density functional theory (DFT) calculations and experimental characterization. Our results demonstrate the potential of symbolic classification for accelerating the data-driven design and discovery of materials with improved properties.