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Post-extraction alveolar bone atrophy greatly hinders the subsequent orthodontic tooth movement (OTM) or implant placement. In this study, we synthesized biodegradable bifunctional bioactive calcium phosphorus nanoflowers (NFs) loaded with abaloparatide (ABL), namely ABL@NFs, to achieve spatiotemporal management for alveolar bone regeneration. The NFs exhibited a porous hierarchical structure, high drug encapsulation efficacy, and desirable biocompatibility. ABL was initially released to recruit stem cells, followed by sustained release of Ca2+and PO43–for in situinterface mineralization, establishing an osteogenic “biomineralized environment”. ABL@NFs successfully restored morphologically and functionally active alveolar bone without affecting OTM. In conclusion, the ABL@NFs demonstrated promising outcomes for bone regeneration under orthodontic condition, which might provide a desirable reference of man-made “bone powder” in the hard tissue regeneration field.

The comprehension of activity and selectivity origins of the electrooxidation of organics is a crucial knot for the development of a highly efficient energy conversion system that can produce value-added chemicals on both the anode and cathode. Here, we find that the potential-retaining trivalent nickel in NiOOH (Fermi level, −7.4 eV) is capable of selectively oxidizing various primary alcohols to carboxylic acids through a nucleophilic attack and nonredox electron transfer process. This nonredox trivalent nickel is highly efficient in oxidizing primary alcohols (methanol, ethanol, propanol, butanol, and benzyl alcohol) that are equipped with the appropriate highest occupied molecular orbital (HOMO) levels (−7.1 to −6.5 eV vs vacuum level) and the negative dual local softness values (Δsk, −0.50 to −0.19) of nucleophilic atoms in nucleophilic hydroxyl functional groups. However, the carboxylic acid products exhibit a deeper HOMO level (<−7.4 eV) or a positive Δsk, suggesting that they are highly stable and weakly nucleophilic on NiOOH. The combination (HOMO, Δsk) is useful in explaining the activity and selectivity origins of electrochemically oxidizing alcohols to carboxylic acid. Our findings are valuable in creating efficient energy conversions to generate value-added chemicals on dual electrodes.

The heterogeneity of cancer cells disables the single-cell death patterns in subtypes of cells with different genotypes and phenotypes, such as refractory triple-negative breast cancer (TNBC). Therefore, the combination of multiple death modes, such as the proven cooperative apoptosis and ferroptosis, is expected to sensitize in treating TNBC. Herein, carrier-free theranostic ASP nanoparticles (NPs) were designed for wiping out TNBC by synergistic apoptosis and ferroptosis, which was self-assembled by aurantiamide acetate (Aa), scutebarbatine A (SA), and palmitin (P). Structurally, the rigid parent nucleus of SA and hydrophobic chain of P combined with the Aa to form an ordered nanostructure by noncovalent bonding forces. This self-assembly example applies to the design of nanomedicines based on more than two natural products. Notably, enhanced permeability and retention (EPR) effects and mitochondrial–lysosomal targeting empower ASP NPs to pinpoint tumor sites. Especially, Aa and P induced mitochondrial apoptosis of cancer cells, while SA and P inhibited TNBC by ferroptosis and upregulating p53. More interestingly, the combination of Aa, SA, and P enhanced the uptake of ASP NPs by cancer cell membranes. Overall, the three compounds synergize with each other to exert excellent anticancer effects.

The strategy to expand the recognition spectrum of plant nucleotide-binding domain leucine-rich repeat (NLR) proteins by modifying their recognition sequences is generally limited and often unsuccessful. Kourelis et al. introduced a groundbreaking approach for generating a customized immune receptor, called Pikobody. This method involves integrating a nanobody domain of a fluorescent protein (FP) into a plant NLR. Their research demonstrates that the resulting Pikobody successfully initiates an immune response against diverse pathogens when exposed to the corresponding FP.

Phenolamide (PA) metabolites play important roles in the interaction between plants and pathogens. The putrescine hydroxycinnamoyl transferase genes OsPHT3and OsPHT4positively regulate rice cell death and resistance to Magnaporthe oryzae. The bZIP transcription factor APIP5, a negative regulator of cell death and rice immunity, directly binds to the OsPHT4promoter to regulate putrescine-derived PAs. Whether other hydroxycinnamoyl transferase (HT) genes also participate in APIP5-mediated immunity remains unclear. Surprisingly, we find that genes encoding agmatine hydroxycinnamoyl transferases OsAHT1 and OsAHT2, tryptamine hydroxycinnamoyl transferases OsTBT1 and OsTBT2, and tyramine hydroxycinnamoyl transferases OsTHT1 and OsTHT2, responsible for the biosynthesis of polyamine-derived PAs are all up-regulated in APIP5-RNAi transgenic plants compared with segregated wild-type rice. Furthermore, both OsAHT1/2and OsTBT1/2are induced during M. oryzaeinfection, showing expression patterns similar to those previously reported for OsTHT1/2and OsPHT3/4. Transgenic plants overexpressing either OsAHT2-GFPor OsTBT1-GFPshow enhanced resistance against M. oryzaeand accumulated more PA metabolites and lignin compared with wild-type plants. Interestingly, as demonstrated for OsPHT4, APIP5 directly binds to the promoters of OsAHT1/2, OsTBT1/2, and OsTHT1/2, repressing their transcription. Together, these results indicate that the HT genes are common targets of APIP5 and that PAs play critical roles in rice immunity.

The oxidative desulphurization process based on V-Mn bimetal sites in confined mesopore bears free radical participation and ring-forming reaction mechanisms together, where Mn site acted as free radicals triggering center which was further optimized by surrounded V sites to promote the reaction.

The nitrate-denitrifying anaerobic methane oxidation (nitrate-DAMO) process is a methane anaerobic oxidation coupled denitrification process, in which methane is the only carbon source and nitrate or nitrite is the electron acceptor. Sulfate can coexist with nitrate-DAMO microorganisms in natural water and sewage. In order to find out the effect of sulfate on the nitrate-DAMO process, experiments were conducted from the macro to the micro scale. The results showed that the denitrification rate of the nitrate-DAMO system was increased first and then decreased with the increase of sulfate concentration from 0 to 380 mg SO42−per L. The nitrate-DAMO system was slightly promoted by the sulfate concentration of 40 mg SO42−per L, and the system was inhibited when the sulfate concentration was increased from 80 to 380 mg SO42−per L. There was no sulfate consumed in the nitrate-DAMO system, which showed that no sulfate reduction coupled methane anaerobic oxidation occurred during the tests. The production and consumption of methanol were not significantly affected by 40 mg SO42−per L sulfate, but when the sulfate was increased to 80 mg SO42−per L, the methanol concentration decreased. SEM results showed that the nitrate-DAMO microorganisms produced more extracellular polymeric substances (EPS) to promote the accumulation of individual cells under sulfate stress. Quantitative polymerase chain reaction analysis showed that the ANME-2d gene abundance increased by 100.01% under the influence of 40 mg SO42−per L sulfate compared with the control group and decreased by 50.41% under the influence of 80 mg SO42−per L sulfate. Then, the pmoA gene abundance increased by 14.50% under the influence of 40 mg SO42−per L sulfate compared with the control group and decreased by 21.67% under the influence of 80 mg SO42−per L sulfate.

Photocatalytic CO2conversion into carbonaceous fuels through artificial photosynthesis is beneficial to global warming mitigation and renewable resource generation. However, a high cost is always required by special CO2-capturing devices for efficient artificial photosynthesis. For achieving highly efficient photocatalytic CO2reduction (PCR) directly from natural air, we report rose-like BiOCl that is rich in Bi vacancies (VBi) assembled by nanosheets with almost fully exposed active {001} facets. These rose-like BiOCl with VBiassemblies provide considerable adsorption and catalytic sites, which hoists the CO2capture and reduction capabilities, and thus expedites the PCR to a superior value of 21.99 μmol·g–1·h–1CO generation under a 300 W Xe lamp within 5 h from natural air. The novel design and construction of a photocatalyst in this work could break through the conventional PCR system requiring compression and purification for CO2, dramatically reduce expenses, and open up new possibilities for the practical application of artificial photosynthesis.

Understanding the effects of antibiotics on enhanced biological phosphorus removal (EBPR), which has been widely accepted as the most economical and sustainable process for removing phosphorus from wastewater to control eutrophication problems, is very important. The potential role of ciprofloxacin (CIP) in inhibiting wastewater phosphorus removal during short-term exposure and the associated mechanisms were investigated in this study. The results showed that the inhibitory effect of CIP on phosphorus removal efficiency was dose- and time-dependent. Total extracellular polymeric substances and polysaccharide (PS) production were immediately enhanced as the CIP concentration increased, implying that PS was secreted to resist toxicity. However, these parameters decreased with increasing reaction cycles. Reactive oxygen species (ROS) increased remarkably during the aerobic phase, resulting in a decreased oxygen uptake rate. Moreover, variations in stoichiometric parameters and kinetic rates showed that anaerobic and aerobic metabolism was affected by CIP, with the aerobic metabolism of phosphate-accumulating organisms being more sensitive to CIP than anaerobic metabolism, probably due to the increase in ROS. Furthermore, glycogen production was strongly inhibited by CIP, and the tricarboxylic acid cycle might be involved in anaerobic metabolism. The results of this study offer insights into the short-term effects of CIP on biological phosphorus removal from the view of anaerobic and aerobic metabolism, which enables further study on control strategies for reducing CIP inhibition and maximizing the reliability and efficiency of EBPR.

The COVID-19 pandemic underscores the need for rapid, safe, and effective vaccines. In contrast to some traditional vaccines, nanoparticle-based subunit vaccines are particularly efficient in trafficking antigens to lymph nodes, where they induce potent immune cell activation. Here, we developed a strategy to decorate the surface of oxidation-sensitive polymersomes with multiple copies of the SARS-CoV-2 spike protein receptor-binding domain (RBD) to mimic the physical form of a virus particle. We evaluated the vaccination efficacy of these surface-decorated polymersomes (RBDsurf) in mice compared to RBD-encapsulated polymersomes (RBDencap) and unformulated RBD (RBDfree), using monophosphoryl-lipid-A-encapsulated polymersomes (MPLA PS) as an adjuvant. While all three groups produced high titers of RBD-specific IgG, only RBDsurfelicited a neutralizing antibody response to SARS-CoV-2 comparable to that of human convalescent plasma. Moreover, RBDsurfwas the only group to significantly increase the proportion of RBD-specific germinal center B cells in the vaccination-site draining lymph nodes. Both RBDsurfand RBDencapdrove similarly robust CD4+and CD8+T cell responses that produced multiple Th1-type cytokines. We conclude that a multivalent surface display of spike RBD on polymersomes promotes a potent neutralizing antibody response to SARS-CoV-2, while both antigen formulations promote robust T cell immunity.

Intelligent systems that offer traceable cancer therapy are highly desirable for precision medicine. Although photodynamic therapy (PDT) has been approved in the clinic for decades, determining where the tumor is, when to irradiate, and how long to expose to light still confuse the clinicians. Patients are always suffering from the phototoxicity of the photosensitizer in nonmalignant tissues. Herein, an activatable theranostic agent, ZnPc@TPCB nanoparticles (NPs), is prepared by doping a photosensitizer, ZnPc, with an aggregation-induced emission probe, TPCB. The assembled or disassembled ZnPc@TPCB NPs in various phases have behaved differently in fluorescence intensity, photoacoustic (PA) signals, and PDT efficiency. The intact nanoparticles are non-emissive in aqueous media while showing strong PA signals and low PDT efficiency, which can eliminate the phototoxicity and self-monitor their distribution and image the tumors’ location. Disassembling of the NPs leads to the release of ZnPc and its red fluorescence turn-on to self-report the photosensitizer’s activation. Upon light irradiation, the reactive oxygen species (ROS) generated by ZnPc can induce cell apoptosis and activate the ROS sensor, TPCB, which will yield intense orange-red fluorescence and instantly predict the therapeutic effect. Moreover, enhanced PDT efficacy is achieved viathe GSH-depleting adjuvant quinone methide produced by the activated TPCB. The well-designed ZnPc@TPCB NPs have shown promising potential for finely controlled PDT with good biosafety and broad application prospects in individual therapy, which may inspire the development of precision medicine.

The pan-cancer detection and precise visualization of tiny tumors in surgery still face great challenges. As tumors grow aggressively, hypoxia is a common feature of solid tumors and has supplied a general way for detecting tumors. Herein, we report a simple aggregation-induced emission nanoprobe-TPE-4NE-O that can specifically switch on their fluorescence in the presence of cytochrome P450 reductase, a reductase which is overexpressed under hypoxia conditions. The probe can selectively light up the hypoxia cells and has shown enhanced deep tumor penetration via charge conversion both in vitroand in vivo. After being modified with FA-DSPE-PEG, higher tumor uptake can be seen and FA-DSPE/TPE-4NE-O showed specific visualization to the hypoxia cancer cells. Excitingly, much brighter fluorescence was accumulated at the tumors in the FA-DSPE/TPE-4NE-O group, even though the tumor was as small as 2.66 mm. The excellent performance of FA-DSPE/TPE-4NE-O in detecting tiny tumors has made it possible for imaging-guided tumor resection. More importantly, the probe exhibited good biocompatibility with negligible organ damage and eliminated a hemolysis risk. The simple but promising probe has supplied a new strategy for pan-cancer detection and tiny tumor visualization, which have shown great potential in clinical translation.

Short half-life is one of the main causes of drug attrition in clinical development, which also leads to the failure of many leading compounds and hits to become drug candidates. Nowadays, nanomaterials have been applied to drug development to address this problem. In fact, the clinical application of nanoparticles (NPs) is severely limited due to their rapid elimination by the reticuloendothelial system (RES) in vivo. In this paper, we aim to summarize representative strategies on prolonging the circulation time for bridging the gap between excellent pharmaceutics and proper half-life and encourage clinical translation.

Microbial fuel cells (MFCs), capable of concurrently treating sulfide and nitrate while generating electricity, were evaluated with various influent sulfide to nitrate molar ratios (S:N ratios). All MFCs displayed a good substrate removal capacity regardless of the S:N ratio (i.e., 5:0, 5:1, 5:2, and 5:3) and produced nitrogen gas, elemental sulfur, and sulfate as major products, while low S:N ratios mediated high sulfate conversion. By setting the S:N ratio to 5:2, the electricity generation was maximized, which was consistent with cyclic voltammetry (CV) curves. Through high-throughput sequencing, the taxonomic distribution of a microbial community in suspended sludge was analyzed; the diversity indices and a principal component analysis (PCA) suggest that the S:N ratios may affect the microbial community in MFCs. However, a Pearson correlation analysis infers that the S:N ratios do not have a significant impact on the richness and diversity of the microbial communities in MFCs involved in the simultaneous treatment of sulfide and nitrate (p> 0.05).

Photodynamic therapy (PDT), a clinically approved cancer treatment, has faced many drawbacks that restricted its applications. For example, the hypoxia-induced elevated hypoxia-inducible factor-1α (HIF-1α) may desensitize tumors to PDT, and the high concentration of glutathione (GSH) in cancer cells can also neutralize the generated reactive oxygen species (ROS) during PDT, resulting in insufficient therapy. Moreover, extra probes for imaging-guided visualization therapy are always needed to track drug release or distribution, while it may decrease the drug loading of the drug delivery system (DDS). In the present study, we have designed and prepared a novel multifunctional combined therapy nanoparticle (ZnPc@Cur-S-OA NPs), in which curcumin (Cur) was not only used as a chemotherapy drug to achieve a combination therapy with PDT via downregulating HIF-1α and depleting GSH in B16F10 cells but also designed as a small-molecule ROS-triggered release prodrug to deliver the photosensitizer (PS). The red fluorescence of PS in the nanoparticles (NPs) can be used to track the NPs distribution, while the green fluorescence of Cur showed an “OFF–ON” activation, which enables additional imaging and real-time self-monitoring capabilities. These results proved that the prepared combined therapy NPs were more effective to inhibit the growth of B16F10 mouse melanoma tumor than was monotherapy without eliciting systemic toxicity either in vitroor in vivo, which indicated the combined therapy NPs as an effective way to improve the PDT efficacy via downregulation of HIF-1α and depletion of GSH. Thus, the strategy of using a multifunctional natural product as the stimuli-responsive carrier as well as the synergist with PDT for enhancing antitumor efficacy via multiple pathways may open an alternative avenue to fabricate new self-delivery combination therapy nanodrugs. Besides, the fluorescence emitted from the drug can be used for real-time self-monitoring of drug release and distribution, which has great potential in clinic to adjust the administration dose and irradiation time for different tumor types and stages for individual therapy.

Ternary metal sulfides have excellent light absorption properties, but their high recombination rate of photo generated carriers limits their practical application. To address this problem, this work constructed a novel nanoflower−like AgIn5S8/ZnIn2S4heterojunction and explored its removal performance for Cr(VI) in water. AgIn5S8was prepared by the solvothermal method, whereas ZnIn2S4and AgIn5S8/ZnIn2S4heterojunction was synthesized via the hydrothermal method. The morphological characteristics of AgIn5S8/ZnIn2S4heterojunction showed that the AgIn5S8particles uniformly distributed on the surface of ZnIn2S4with a flower like structure. The obtained 10% AgIn5S8/ZnIn2S4exhibited a higher specific surface area (75.07 m2/g) than AgIn5S8(20.91 m2/g) and ZnIn2S4(58.30 m2/g), with the maximum Cr(VI) removal efficiency of 88.5% at an initial concentration of 20mg/L. The photocatalytic reduction of Cr(VI) by AgIn5S8/ZnIn2S4conformed to the pseudo-first-order kinetic model. The superoxide radicals (·O2−) and photogenerated electrons (e−) were identified as the major active substances for Cr(VI) photoreduction according to the electron paramagnetic resonance (EPR) and free radical trapping experiments. The Mott−Schottky analysis demonstrated that the band structures of AgIn5S8and ZnIn2S4were compatible. Density functional theory (DFT) calculations showed that AgIn5S8/ZnIn2S4heterojunction enhanced the separation efficiency of photogenerated carriers through an internal electric field (IEF). These results demonstrate that type–II AgIn5S8/ZnIn2S4heterojunctions have the potential for effective removal of Cr(VI) in wastewater under visible light irradiation.

Fully effective vaccines for complex infections must elicit a diverse repertoire of antibodies (humoral immunity) and CD8+T-cell responses (cellular immunity). Here, we present a synthetic glyco-adjuvant named p(Man–TLR7), which, when conjugated to antigens, elicits robust humoral and cellular immunity. p(Man–TLR7) is a random copolymer composed of monomers that either target dendritic cells (DCs) via mannose-binding receptors or activate DCs via Toll-like receptor 7 (TLR7). Protein antigens are conjugated to p(Man–TLR7) via a self-immolative linkage that releases chemically unmodified antigen after endocytosis, thus amplifying antigen presentation to T cells. Studies with ovalbumin (OVA)–p(Man–TLR7) conjugates demonstrate that OVA–p(Man–TLR7) generates greater humoral and cellular immunity than OVA conjugated to polymers lacking either mannose targeting or TLR7 ligand. We show significant enhancement of Plasmodium falciparum-derived circumsporozoite protein (CSP)-specific T-cell responses, expansion in the breadth of the αCSP IgG response and increased inhibition of sporozoite invasion into hepatocytes with CSP–p(Man–TLR7) when compared with CSP formulated with MPLA/QS-21-loaded liposomes—the adjuvant used in the most clinically advanced malaria vaccine. We conclude that our antigen–p(Man–TLR7) platform offers a strategy to enhance the immunogenicity of protein subunit vaccines.

In this paper, we evaluated the oxygen reduction reaction (ORR) activities of Pt/C, PtCo/C, and PtCoMn/C catalysts using charge-transfer resistance (Rct) and DRct onset voltage from electrochemical impedance spectroscopy as indicators in proton exchange membrane fuel cells (PEMFC) over a wide voltage range of 0.66 V[?]0.95 V. ORR activity of the PtCoMn/C ternary alloy catalyst is higher than that of Pt/C over a large voltage range. A decal transfer method was used to prepare a membrane electrode assembly (MEA) with PtCoMn/C as a cathode catalyst. The cross-sectional micrograph of MEA-PtCoMn/C was characterized using scanning electron microscopy. A continuous ultrathin cathode catalyst layer that was 3 um thick was successfully prepared. The performance of MEA-PtCoMn/C with an ultralow Pt loading of 0.147 mg/cm2 was evaluated using the single cell test. The highest achieved power density of MEA-PtCoMn/C was 1.42 W/cm2. The corresponding amount of platinum was 0.1035 gPt/kW, which reaches the index of the Department of Energy (DOE).

The poor durability of proton exchange membrane fuel cells still is their greatest barrier preventing commercialization. In this paper, we perform a 1465 h in situ durability test with a single fuel cell operating at a constant-current of 800mA cm[?]2. Polarization curves, cyclic voltammetry, and electrochemical impedance spectroscopy are used for diagnostics and to understand changes in performance during the test. Limiting current method is used to analyze the oxygen transport resistance of the gas diffusion layer (GDL) before and after durability test. The results indicate that the oxygen transport resistance in single cell increases greatly, and GDL is the first component leading to fuel cell failure after1465h test. At 150 kPa and 20% dry oxygen mole fraction, the limiting current decreases to about 700mA cm[?]2 and total oxygen transport resistance increases by 0.1623s cm[?]1, implying more serious flooding occurs in GDL after the 1465 h durability test. The increase of oxygen transport resistances of the substrate and micro porous layer of GDL confirm the loss of water management capability of GDL. SEM images show that these may be caused by oxidation of carbon and loss of polytetrafluoroethylene in GDL.

ABSTRACTThe codon usage pattern can reveal the adaptive changes that allow virus survival and fitness adaptation to their particular host, as well as the external environment. Although still considered a novel influenza virus, there is an increasing number of influenza D viruses (IDVs) reported. Considering the vital role of the hemagglutinin-esterase fusion (HEF) gene in receptor binding, receptor degradation, and membrane fusion, we investigated the codon usage pattern of the IDV HEF gene to better understand its adaptive changes during evolution. Based on the HEF gene, three groups including, D/OK, D/660, and D/Japan were identified. We found a low codon usage bias, which allowed IDV to replicate in the corresponding hosts by reducing competition during evolution, that was mainly driven by natural selection and mutation pressure, with a profound role of natural selection. Furthermore, the interaction between the codon adaption index (CAI) and the relative codon deoptimization index (RCDI) revealed the adaption of IDV to multiple hosts, especially cattle which is currently considered its reservoir. Additionally, similarity index (SiD) analysis revealed that the swine exerted a stronger evolutionary pressure on IDV than cattle, though cattle is considered the primary reservoir. In addition, the conserved PB1 gene showed a similar pattern of codon usage compared to HEF. Therefore, we hypothesized that IDV has a preference to maintain infection in multiple hosts. The study aids the understanding of the evolutionary changes of IDV, which could assist this novel virus prevention and control.

The receptor protein PEX5, an important component of peroxisomes, regulates growth, development, and immunity in yeast and mammals. PEX5 also influences growth and development in plants, but whether it participates in plant immunity has remained unclear. Here, we report that knockdown of OsPEX5enhances resistance to the rice blast fungus Magnaporthe oryzae. We demonstrate that OsPEX5 interacts with the E3 ubiquitin ligase APIP6, a positive regulator of plant immunity. APIP6 ubiquitinates OsPEX5 in vitroand promotes its degradation in vivovia the 26S proteasome pathway. In addition, OsPEX5 interacts with the aldehyde dehydrogenase OsALDH2B1, which functions in growth-defense trade-offs in rice. OsPEX5 stabilizes OsALDH2B1 to enhance its repression of the defense-related gene OsAOS2. Our study thus uncovers a previously unrecognized hierarchical regulatory mechanism in which an E3 ubiquitin ligase targets a peroxisome receptor protein that negatively regulates immunity in rice by stabilizing an aldehyde dehydrogenase that suppresses defense gene expression.

Butyrate is a key bacterial metabolite that plays an important and complex role in modulation of immunity and maintenance of epithelial barriers. Its translation to clinic is limited by poor bioavailability, pungent smell, and the need for high doses, and effective delivery strategies have yet to realize clinical potential. Here, a novel polymeric delivery platform for tunable and sustainable release of butyrate consisting of a methacrylamide backbone with butyryl ester or phenyl ester side chains as well as mannosyl side chains, which is also applicable to other therapeutically relevant metabolites is reported. This platform's utility in the treatment of non‐healing diabetic wounds is explored. This butyrate‐containing material modulated immune cell activation in vitro and induced striking changes in the milieu of soluble cytokine and chemokine signals present within the diabetic wound microenvironment in vivo. This novel therapy shows efficacy in the treatment of non‐healing wounds through the modulation of the soluble signals present within the wound, and importantly accommodates the critical temporal regulation associated with the wound healing process. Currently, the few therapies to address non‐healing wounds demonstrate limited efficacy. This novel platform is positioned to address this large unmet clinical need and improve the closure of otherwise non‐healing wounds. A novel delivery platform for the temporally controlled release of the microbial metabolite butyrate to accelerate the healing of chronic wounds is reported. Butyrate is implicated in the improvement of barrier function and is here employed to address the large clinical problem of non‐healing cutaneous wounds.

The promotion of magnetic field on catalytic performance has attracted extensive attention for a long time, and substantial improvements have been achieved in some catalysis fields. However, because the Zeeman energy is several orders of magnitude weaker, magnetic field seems unable to alter the band structure and has a negligible effect on semiconductor photocatalytic performance, which makes this task a great challenge. On the other hand, the spin-related behavior usually plays an important role in determining catalytic performance. For example, in some molecular catalysis, such as photosystem II, ferromagnetic alignment of the active material results in spin-oriented electrons, which are selected and accumulated at the interface, leading to great promotion of the oxygen evolution reaction activity. Here, we propose a magnetoresistance-related strategy to boost the carrier transfer efficiency and apply it in α-Fe2O3/reduced graphene oxide hybrid nanostructures (α-Fe2O3/rGO) to improve the photocatalytic performance under magnetic field. We show that both the degradation rate constant and photocurrent density of α-Fe2O3/rGO can be dramatically enhanced with the application of magnetic field, indicating the promotion of the photocatalytic performance.

Due to the capacity to quantify the complexity of a fracture network, fractal dimension (D) is widely applied in analyzing fracture network-related issues, such as connectivity and permeability. While the relationship between Dand individual properties of a fracture network has been extensively studied, Dis influenced by a combination of multiple attributes of the fracture network. Therefore, this work utilizes multivariate analysis to establish an equation for predicting D, taking into account various properties of the fracture network, namely fracture length, number, and orientation. Monte Carlo simulation is employed to generate a substantial number of fracture network models. Subsequently, relationships between the fractal dimension (D) and various properties are derived for three types of fracture networks with (1) invariant fracture length and random orientation, (2) exponential fracture length and random orientation, and (3) exponential fracture length and von-Mises orientation. The initial analysis focuses on the simplest relationship, wherein the fundamental formula of fractional expression is determined. Then the second and third relationships are obatiend though replacning by the fixed parameter in the first relationship by the distribution parameters of fracture properties. Correlation analyses between the predicted Dand the actual values reveal a remarkably high correlation (>0.99). To validate the established relationships, a fracture network obtained from geological outcrops is utilized. The results demonstrate the validity of the derived relationships. The utilization of these equations enhances the efficiency, practicality, and convenience of estimating fractal dimensions from fracture properties. As a result, the analysis of fracture network-related issues becomes more feasible and accessible.

ObjectiveTo evaluate the quality of evidence, potential biases, and validity of all available studies on dietary sugar consumption and health outcomes.DesignUmbrella review of existing meta-analyses.Data sourcesPubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and hand searching of reference lists.Inclusion criteriaSystematic reviews and meta-analyses of randomised controlled trials, cohort studies, case-control studies, or cross sectional studies that evaluated the effect of dietary sugar consumption on any health outcomes in humans free from acute or chronic diseases.ResultsThe search identified 73 meta-analyses and 83 health outcomes from 8601 unique articles, including 74 unique outcomes in meta-analyses of observational studies and nine unique outcomes in meta-analyses of randomised controlled trials. Significant harmful associations between dietary sugar consumption and 18 endocrine/metabolic outcomes, 10 cardiovascular outcomes, seven cancer outcomes, and 10 other outcomes (neuropsychiatric, dental, hepatic, osteal, and allergic) were detected. Moderate quality evidence suggested that the highest versus lowest dietary sugar consumption was associated with increased body weight (sugar sweetened beverages) (class IV evidence) and ectopic fatty accumulation (added sugars) (class IV evidence). Low quality evidence indicated that each serving/week increment of sugar sweetened beverage consumption was associated with a 4% higher risk of gout (class III evidence) and each 250 mL/day increment of sugar sweetened beverage consumption was associated with a 17% and 4% higher risk of coronary heart disease (class II evidence) and all cause mortality (class III evidence), respectively. In addition, low quality evidence suggested that every 25 g/day increment of fructose consumption was associated with a 22% higher risk of pancreatic cancer (class III evidence).ConclusionsHigh dietary sugar consumption is generally more harmful than beneficial for health, especially in cardiometabolic disease. Reducing the consumption of free sugars or added sugars to below 25 g/day (approximately 6 teaspoons/day) and limiting the consumption of sugar sweetened beverages to less than one serving/week (approximately 200-355 mL/week) are recommended to reduce the adverse effect of sugars on health.Systematic review registrationPROSPERO CRD42022300982.

Low molecular weight heparin (LMWH) shows great anticoagulant effect for prevention and treatment of deep venous thrombosis. However, its oral administration is seriously hindered by multiple obstacles. In this study, a pH-responsive delivery system was developed to protect LMWH from gastrointestinal tract degradation and facilitate its absorption across gastrointestinal mucosa. The LMWH-loaded nanoparticles (pH-TCS/O-CMCS@LMWH) were prepared by ionic-crosslinking reaction between positive-charged amino groups of thiolated chitosan (TCS) as well as o-carboxymethyl chitosan (O-CMCS) and oppositely charged HP55. As a result, the prepared nanoparticles proved to spherical shape with an average size of 332 nm, high encapsulation efficiency of 96.6% and drug-loading content of 12.04 IU/mg. The proposed pH-TCS/O-CMCS@LMWH also showed good colloidal stability, potential mucoadhesive effect and desirable pH-responsive drug release behavior, which decreased pre-mature LMWH release in acidic environment but increase its targeted release in intestine environment. After oral administration, the pH-TCS/O-CMCS@LMWH shown enhanced bioavailability and significant antithrombotic effect in a rat model of venous thrombosis. In conclusion, pH-TCS/O-CMCS nanoparticles can be successfully hold great promising for oral administration of LMWH and potential treatment for thrombosis.

Background: Ubiquitination is essential for many cellular processes in eukaryotes, including 26S proteasome-dependent protein degradation, cell cycle progression, transcriptional regulation, and signal transduction. Although numerous ubiquitinated proteins have been empirically identified, their cognate ubiquitin E3 ligases remain largely unknown. Results: Here, we generate a complete ubiquitin E3 ligase-encoding open reading frames (UbE3-ORFeome) library containing 98.94% of the 1515 E3 ligase genes in the rice (Oryza sativaL.) genome. In the test screens with four known ubiquitinated proteins, we identify both known and new E3s. The interaction and degradation between several E3s and their substrates are confirmed in vitro and in vivo. In addition, we identify the F-box E3 ligase OsFBK16 as a hub-interacting protein of the phenylalanine ammonia lyase family OsPAL1–OsPAL7. We demonstrate that OsFBK16 promotes the degradation of OsPAL1, OsPAL5, and OsPAL6. Remarkably, we find that overexpression of OsPAL1or OsPAL6as well as loss-of-function of OsFBK16in rice displayed enhanced blast resistance, indicating that OsFBK16 degrades OsPALs to negatively regulate rice immunity. Conclusions: The rice UbE3-ORFeome is the first complete E3 ligase library in plants and represents a powerful proteomic resource for rapid identification of the cognate E3 ligases of ubiquitinated proteins and establishment of functional E3–substrate interactome in plants.

Gambogic acid (GA) has been approved to enter the phase III clinical trial. However, due to its short half-life, low water solubility, poor stability and inflammatory response, GA failed to pass the clinical superiority evaluation. Nano-preparations perform well in prolonging drug half-life, improving drug solubility, and enhancing drug stability etc. Therefore, a self-assembled nanoparticle (GA-HES/NPs) with long circulation and deep tumor penetration ability was designed, in which hydroxyethyl starch (HES) endowed GA-HES/NPs with longer circulation time as well as deep tumor penetration ability, and the simple synthesis method ensured the stability of GA structure. Experimental results showed that GA-HES/NPs owned a certain tumor targeting and deep tumor penetration ability, as well as longer circulation time, which could enhance the therapeutic effect of GA.

Rice blast and bacterial blight, caused by the fungus Magnaporthe oryzaeand the bacterium Xanthomonas oryzaepv. oryzae(Xoo), respectively, are devastating diseases affecting rice. Here, we report that a rice valine-glutamine (VQ) motif-containing protein, OsVQ25, balances broad-spectrum disease resistance and plant growth by interacting with a U-Box E3 ligase, OsPUB73, and a transcription factor, OsWRKY53. We show that OsPUB73 positively regulates rice resistance against M. oryzaeand Xooby interacting with and promoting OsVQ25 degradation via the 26S proteasome pathway. Knockout mutants of OsVQ25exhibit enhanced resistance to both pathogens without a growth penalty. Furthermore, OsVQ25 interacts with and suppresses the transcriptional activity of OsWRKY53, a positive regulator of plant immunity. OsWRKY53 downstream defense-related genes and brassinosteroid signaling genes are upregulated in osvq25mutants. Our findings reveal a ubiquitin E3 ligase-VQ protein-transcription factor module that fine-tunes plant immunity and growth at the transcriptional and posttranslational levels.

Background: Balancing the yield, quality and resistance to disease is a daunting challenge in crop breeding due to the negative relationship among these traits. Large-scale genomic landscape analysis of germplasm resources is considered to be an efficient approach to dissect the genetic basis of the complex traits. Central China is one of the main regions where the japonicarice is produced. However, dozens of high-yield rice varieties in this region still exist with low quality or susceptibility to blast disease, severely limiting their application in rice production. Results: Here, we re-sequence 200 japonicarice varieties grown in central China over the past 30 years and analyze the genetic structure of these cultivars using 2.4 million polymorphic SNP markers. Genome-wide association mapping and selection scans indicate that strong selection for high-yield and taste quality associated with low-amylose content may have led to the loss of resistance to the rice blast fungus Magnaporthe oryzae. By extensive bioinformatic analyses of yield components, resistance to rice blast, and taste quality, we identify several superior alleles for these traits in the population. Based on this information, we successfully introduce excellent taste quality and blast-resistant alleles into the background of two high-yield cultivars and develop two elite lines, XY99 and JXY1, with excellent taste, high yield, and broad-spectrum of blast resistance. Conclusions: This is the first large-scale genomic landscape analysis of japonicarice varieties grown in central China and we demonstrate a balancing of multiple agronomic traits by genomic-based strategy.

With the development of automobile industry technology, the production of waste tires (WTs) has been increasing rapidly, resulting in serious environmental damage and great treatment pressure. In this work, co-combustion of WT and coal under different mixing ratios were investigated to figure out the thermal property and heavy metals (HMs) migration in thermal treatment process. Besides, the chemical composition and leachability of ash samples were investigated. The results revealed that the addition of WT reduced the ignition temperature of the blend. Comprehensive combustion index (CCI) was higher than mono-combustion of coal and theoretical value with adding 20% WT, indicating there existed the synergistic effect between two fuels. Compared with coal ash, WT ash performed lower volatilization ratios of Zn, Cu, Ni and Cr. Furthermore, the volatilization of Cr/Ni decreased with the addition of WT. According to the comparison between theoretical and experimental values of Zn volatilization ratio, the Zn volatilization was promoted. However, there still had large amount of Zn fixed in ash to form minerals in co-combustion. In addition, leachability of both Zn and Cu and mixing ratio presented positive correlation. Leachability of both Cr and Ni in co-combustion ash were higher than that of mono-combustion ash.

Membrane electrode assembly (MEA) is a core component of fuel cells, and its durability constitutes the bottleneck of fuel cells commercialization. In this paper, the effects of relative humidification (RH) on durability of membrane electrode assembly (MEA) are studied by the limiting current method. In-situ durability tests are carried out for 2040 h under constant current density of 800 mA cm?2and relative humidification (RH) of 70%. The results are then compared to those of our previously published 1465h-MEA obtained for 1465 h under 100% humidification. The degradation in the voltage during the process is analyzed, and degradation mechanisms are investigated by electrochemical impedance spectroscopy and limiting current methods to analyze the change in oxygen transport resistance of the gas diffusion layer. The data suggest that the decline in the humidification can greatly improve the durability of MEAs, especially from 0 to 1000 h. The voltage decay rate of 2040h-MEA is half that of 1465h-MEA. The main degradation occurs in the substrate layer after durability tests for 2040 h under 70%RH. By comparison, 1465h-MEA operating at 100% RH shows a serious decay not only in the substrate layer but also in the MPL, as confirmed by the changes in contact angles.

The poor durability of proton exchange membrane fuel cells still is their greatest barrier preventing commercialization. In this paper, we perform a 1465 h in situ durability test with a single fuel cell operating at a constant-current of 800mA cm−2. Polarization curves, cyclic voltammetry, and electrochemical impedance spectroscopy are used for diagnostics and to understand changes in performance during the test. Limiting current method is used to analyze the oxygen transport resistance of the gas diffusion layer (GDL) before and after durability test. The results indicate that the oxygen transport resistance in single cell increases greatly, and GDL is the first component leading to fuel cell failure after1465h test. At 150 kPa and 20% dry oxygen mole fraction, the limiting current decreases to about 700mA cm−2and total oxygen transport resistance increases by 0.1623s cm−1, implying more serious flooding occurs in GDL after the 1465 h durability test. The increase of oxygen transport resistances of the substrate and micro porous layer of GDL confirm the loss of water management capability of GDL. SEM images show that these may be caused by oxidation of carbon and loss of polytetrafluoroethylene in GDL.

In this paper, we evaluated the oxygen reduction reaction (ORR) activities of Pt/C, PtCo/C, and PtCoMn/C catalysts using charge-transfer resistance (Rct) and ΔRctonset voltage from electrochemical impedance spectroscopy as indicators in proton exchange membrane fuel cells (PEMFC) over a wide voltage range of 0.66 V∼0.95 V. ORR activity of the PtCoMn/C ternary alloy catalyst is higher than that of Pt/C over a large voltage range. A decal transfer method was used to prepare a membrane electrode assembly (MEA) with PtCoMn/C as a cathode catalyst. The cross-sectional micrograph of MEA-PtCoMn/C was characterized using scanning electron microscopy. A continuous ultrathin cathode catalyst layer that was 3 μm thick was successfully prepared. The performance of MEA-PtCoMn/C with an ultralow Pt loading of 0.147 mg/cm2was evaluated using the single cell test. The highest achieved power density of MEA-PtCoMn/C was 1.42 W/cm2. The corresponding amount of platinum was 0.1035 gPt/kW, which reaches the index of the Department of Energy (DOE).