Stable triangle: nanomedicine-based synergistic application of phototherapy and immunotherapy for tumor treatment.

In recent decades, cancer has posed a challenging obstacle that humans strive to overcome. While phototherapy and immunotherapy are two emerging therapies compared to traditional methods, they each have their advantages and limitations. These limitations include easy metastasis and recurrence, low response rates, and strong side effects. To address these issues, researchers have increasingly focused on combining these two therapies by utilizing a nano-drug delivery system due to its superior targeting effect and high drug loading rate, yielding remarkable results. The combination therapy demonstrates enhanced response efficiency and effectiveness, leading to a preparation that is highly targeted, responsive, and with low recurrence rates. This paper reviews several main mechanisms of anti-tumor effects observed in combination therapy based on the nano-drug delivery system over the last five years. Furthermore, the challenges and future prospects of this combination therapy are also discussed.

Photothermal nanocomposite reactivate "immune-hot" for triple-negative breast cancer treatment via glutamine metabolism reprograming.

Herein, a photothermal nanocomposite PAI@CB839 nanoparticles (NPs) was constructed to perform a heat-immune therapy for triple-negative breast cancer (TNBC). Firstly, a photothermal agent animated IR780 was modified on a mPEG-NH2 using 4,4'-dicarboxylazobenzene as a linker. The synthesized PAI exhibited superior photothermal efficiency of the IR780 even after assembling in water. As a functional carrier, PAI was used to load and deliver the glutaminase inhibitor CB839 to tumor tissue. In the hypoxic environment of tumor cells, the azo bond would break, triggering the release of cargo. Upon irradiation, the outstanding photothermal properties of IR780 resulted in tumor cell damage. This process could promote immunogenic cell death and program tumor to "immune-hot" condition. Concurrently, CB839 strengthened the antitumor immune response by remodulating the immunosuppressive TME through disturbing Glu abnormal metabolism, which further inhibited TNBC growth and metastasis. In conclusion, PAI@CB839 NPs exhibited great antitumor efficiency, which pave a new way for TNBC therapeutic regimen development.

Enhancing retention and permeation of rapamycin for osteoarthritis therapy using a two-stage drug delivery system.

Osteoarthritis (OA) remains a challenging degenerative joint disease, largely associated with chondrocyte apoptosis during its development. Preserving chondrocytes stands as a promising strategy for OA treatment. Rapamycin (RP) exhibits chondrocyte protection by fostering autophagy. Nevertheless, the swift clearance of intra-articular injections and the dense cartilage extracellular matrix (ECM) hinder RP from effectively reaching chondrocytes. Herein, we developed a "two-stage" drug delivery system (RP@PEG-PA@P-Lipo). This system comprises primary nanoparticles (P-Lipo), liposomes modified with a collagen II targeting peptide (WYRGRLC), and secondary nanoparticles (RP@PEG-PA), PEG-modified PAMAM encapsulating rapamycin (RP). RP@PEG-PA@P-Lipo demonstrates adherence to the cartilage surface with WYRGRLC, substantially prolonging retention within the joint cavity. Subsequently, released RP@PEG-PA can effectively penetrate the cartilage and deliver RP to chondrocytes through small size and charge-driven forces. In vitro and in vivo experiments corroborate its notable therapeutic effects on OA. This study holds promise in offering a novel approach for clinical drug delivery and OA treatment.

Supramolecular nanoparticle loaded with bilirubin enhances cartilage protection and alleviates osteoarthritis via modulating oxidative stress and inflammatory responses.

Osteoarthritis (OA) is a chronic inflammation that gradually leads to cartilage degradation. Prolonged chondrocyte oxidative stress contributes to the development of diseases, including chondrocyte apoptosis, cartilage matrix degradation, and aggravation of articular cartilage damage. Bilirubin (BR) possesses strong antioxidant properties by scavenging reactive oxygen species (ROS) and potent protection effects against inflammation. However, its insolubility and short half-life limit its clinical use. Therefore, we developed a supramolecular system of ε-polylysine (EPL) conjugated by ß-cyclodextrin (ß-CD) on the side chain, and bilirubin was loaded via host-guest interactions, which resulted in the self-assemble of this system into bilirubin-loaded polylysine-ß-cyclodextrin nanoparticle (PB) with improving solubility while reducing toxicity and prolonging medication action time. To explore PB's potential pharmacological mechanisms on OA, we established in vitro and in vivo OA models. PB exerted ROS-scavenging proficiency and anti-apoptotic effects on rat chondrocytes by activating the Nrf2-HO-1/GPX4 signaling pathway. Additionally, PB reprogrammed the cartilage microenvironment by regulating the NF-κB signaling pathway to maintain chondrocyte function. Animal experiments further confirmed that PB had excellent scavenging ability for ROS and inflammatory factors related to charge adsorption with cartilage as well as long retention ability. Together, this work suggests that PB has superior protective abilities with beneficial effects on OA, indicating its great potential for intervention therapy targeting chondrocytes.

The CYP3A inducer dexamethasone affects the pharmacokinetics of sunitinib by accelerating its metabolism in rats.

Sunitinib, a novel anti-tumor small molecule targeting VEGFR, is prescribed for advanced RCC and GISTs. Sunitinib is primarily metabolized by the CYP3A enzyme. It is well-known that dexamethasone serves as a potent inducer of this enzyme system. Nonetheless, the effect of dexamethasone on sunitinib metabolism remains unclear. This study examined the effect of dexamethasone on the pharmacokinetics of sunitinib and its metabolite N-desethyl sunitinib in rats. The plasma levels of both compounds were measured using UHPLC-MS/MS. Pharmacokinetic parameters and metabolite ratio values were calculated. Compare to control group, the low-dose dexamethasone group and high-dose dexamethasone group decreased the AUC(0-t) values of sunitinib by 47 % and 45 %, respectively. Meanwhile, the AUC(0-t) values of N-desethyl sunitinib were increased by 2.2-fold and 2.4-fold in low-dose dexamethasone group and high-dose dexamethasone group, respectively. The CL values for sunitinib were both approximately 45 % higher in the two dexamethasone groups. Remarkably, metabolite ratio values increased over 5-fold in both low-dose dexamethasone group and high-dose dexamethasone group, indicating a significant enhancement of sunitinib metabolism by dexamethasone. Moreover, the total levels of sunitinib and its metabolite are also significantly increased. The impact of interactions on sunitinib metabolism, as observed with CYP3A inducers such as dexamethasone, is a crucial consideration for clinical practice. To optimize the dosage and prevent adverse drug events, therapeutic drug monitoring can be employed to avoid the toxicity from such interactions.

Insufficient endplate-bone graft contact is a risk factor for high-grade cage subsidence occurring after lateral lumbar interbody fusion supplemented with lateral plate: An analysis of 121 cases.

BACKGROUND: Lateral lumbar interbody fusion (LLIF) is a minimally invasive fusion technique that can be performed with lateral plate. Insufficient contact between the endplate and bone graft may result in cage subsidence. This study aimed to investigate the potential risk factor for high-grade cage subsidence (HCS) occurring after LLIF supplemented with lateral plate. METHODS: Between June 2017 and February 2023, 121 patients (48 males, 73 females; mean age 63.0 years; minimum follow-up period 12 months) undergoing LLIF supplemented with lateral plate were retrospectively reviewed. The incidence of HCS was assessed, and patients were categorized into HCS group or non-HCS group based on the occurrence of HCS. A revision surgery of posterior pedicle screw fixation was performed in patients with cage subsidence and complained with intolerable back pain or radicular symptoms. Comparative analyses were performed on demographic characteristics, surgical variables, and parameters related to endplate-bone graft contact between the two groups. Multivariable logistic regression analysis was employed to identify the potential risk factors associated with HCS. The receiver operating characteristic (ROC) analysis was used to calculate the cutoff values for the risk factors. Clinical outcomes were evaluated using Oswestry Disability Index (ODI), and radiographic fusion at the final follow-up was assessed based on the Bridwell grading system. RESULTS: The HCS group comprised 12 patients, while the non-HCS group included 109 patients. The incidence of HCS occurring after LLIF supplemented with lateral plate was 9.9 %. Compared to non-HCS group, patients in HCS group had lower sagittal and coronal endplate-bone graft contact rates and larger cage-endplate angles. Low sagittal (OR, 1.099; 95 % CI, 1.033-1.169; P=0.003) and low coronal (OR, 1.149, 95 % CI, 1.061-1.243, P=0.001) endplate-bone graft contact rates were determined to be correlated with HCS. The cutoff value of the sagittal and coronal endplate-bone graft contact rate was 63.5 % and 60.9 %. Eleven (91.7 %) patients in HCS group underwent revision posterior pedicle screw fixation. Both HCS and non-HCS groups experienced significant improvements in ODI at the final follow-up, while there were no differences between groups. Ninety-five (87.2 %) patients in non-HCS group, and nine (81.8 %) of the 11 patients who underwent revision surgery in HCS group achieved radiographic fusion at the final follow-up. CONCLUSIONS: The incidence of HCS occurring after LLIF supplemented with lateral plate was 9.9%. Insufficient endplate-bone graft contact is an important risk factor of HCS, and sagittal and coronal endplate-bone graft contact rates can be used as effective predictors for HCS.

Giant Second Harmonic Generation in Supertwisted WS2 Spirals Grown in Step-Edge Particle-Induced Non-Euclidean Surfaces.

In moiré crystals resulting from the stacking of twisted two-dimensional (2D) layered materials, a subtle adjustment in the twist angle surprisingly gives rise to a wide range of correlated optical and electrical properties. Herein, we report the synthesis of supertwisted WS2 spirals and the observation of giant second harmonic generation (SHG) in these spirals. Supertwisted WS2 spirals featuring different twist angles are synthesized on a Euclidean or step-edge particle-induced non-Euclidean surface using carefully designed water-assisted chemical vapor deposition. We observed an oscillatory dependence of SHG intensity on layer number, attributed to atomically phase-matched nonlinear dipoles within layers of supertwisted spiral crystals where inversion symmetry is restored. Through an investigation into the twist angle evolution of SHG intensity, we discovered that the stacking model between layers plays a crucial role in determining the nonlinearity, and the SHG signals in supertwisted spirals exhibit enhancements by a factor of 2 to 136 when compared with the SHG of the single-layer structure. These findings provide helpful perspectives on the rational growth of 2D twisted structures and the implementation of twist angle adjustable endowing them great potential for exploring strong coupling correlation physics and applications in the field of twistronics.

Enhancing oocyte in vitro maturation and quality by melatonin/bilirubin cationic nanoparticles: A promising strategy for assisted reproduction techniques.

In assisted reproduction techniques, oocytes encounter elevated levels of reactive oxygen species (ROS) during in vitro maturation (IVM). Oxidative stress adversely affects oocyte quality, hampering their maturation, growth, and subsequent development. Thus, mitigating excessive ROS to safeguard less viable oocytes during IVM stands as a viable strategy. Numerous antioxidants have been explored for oocyte IVM, yielding considerable effects; however, several aspects, including solubility, stability, and safety, demand attention and resolution. In this study, we developed nanoparticles by self-assembling endogenous bilirubin and melatonin hormone coated with bilirubin-conjugated glycol chitosan (MB@GBn) to alleviate oxidative stress and enhance oocyte maturation. The optimized MB@GBn exhibited a uniform spherical shape, measuring 128 nm in particle size, with a PDI value of 0.1807 and a surface potential of +11.35 mV. The positively charged potential facilitated nanoparticle adherence to the oocyte surface through electrostatic interaction, allowing for functional action. In vitro studies demonstrated that MB@GB significantly enhanced the maturation of compromised oocytes. Further investigation revealed MB@GB's effectiveness in scavenging ROS, reducing intracellular calcium levels, and suppressing mitochondrial polarization. This study not only offers a novel perspective on nano drug delivery systems for biomedical applications but also presents an innovative strategy for enhancing oocyte IVM.

Nanomedicine revolutionizes epilepsy treatment: overcoming therapeutic hurdles with nanoscale solutions.

INTRODUCTION: Epilepsy, a prevalent neurodegenerative disorder, profoundly impacts the physical and mental well-being of millions globally. Historically, antiseizure drugs (ASDs) have been the primary treatment modality. However, despite the introduction of novel ASDs in recent decades, a significant proportion of patients still experiences uncontrolled seizures. AREAS COVERED: The rapid advancement of nanomedicine in recent years has enabled precise targeting of the brain, thereby enhancing therapeutic efficacy for brain diseases, including epilepsy. EXPERT OPINION: Nanomedicine holds immense promise in epilepsy treatment, including but not limited to enhancing drug solubility and stability, improving drug across blood-brain barrier, overcoming resistance, and reducing side effects, potentially revolutionizing clinical management. This paper provides a comprehensive overview of current epilepsy treatment modalities and highlights recent advancements in nanomedicine-based drug delivery systems for epilepsy control. We discuss the diverse strategies used in developing novel nanotherapies, their mechanisms of action, and the potential advantages they offer compared to traditional treatment methods.

Opsonization Inveigles Macrophages Engulfing Carrier-Free Bilirubin/JPH203 Nanoparticles to Suppress Inflammation for Osteoarthritis Therapy.

Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage destruction, synovitis, and osteophyte formation. Disease-modifying treatments for OA are currently lacking. Because inflammation mediated by an imbalance of M1/M2 macrophages in the synovial cavities contributes to OA progression, regulating the M1 to M2 polarization of macrophages can be a potential therapeutic strategy. Basing on the inherent immune mechanism and pathological environment of OA, an immunoglobulin G-conjugated bilirubin/JPH203 self-assembled nanoparticle (IgG/BRJ) is developed, and its therapeutic potential for OA is evaluated. After intra-articular administration, IgG conjugation facilitates the recognition and engulfment of nanoparticles by the M1 macrophages. The internalized nanoparticles disassemble in response to the increased oxidative stress, and the released bilirubin (BR) and JPH203 scavenge reactive oxygen species (ROS), inhibit the nuclear factor kappa-B pathway, and suppress the activated mammalian target of rapamycin pathway, result in the repolarization of macrophages and enhance M2/M1 ratios. Suppression of the inflammatory environment by IgG/BRJ promotes cartilage protection and repair in an OA rat model, thereby improving therapeutic outcomes. This strategy of opsonization involving M1 macrophages to engulf carrier-free BR/JPH203 nanoparticles to suppress inflammation for OA therapy holds great potential for OA intervention and treatment.

Multifunctional iron-apigenin nanocomplex conducting photothermal therapy and triggering augmented immune response for triple negative breast cancer.

Triple negative breast cancer (TNBC) presents a formidable challenge due to its low sensitivity to many chemotherapeutic drugs and a relatively low overall survival rate in clinical practice. Photothermal therapy has recently garnered substantial interest in cancer treatment, owing to its swift therapeutic effectiveness and minimal impact on normal cells. Metal-polyphenol nanostructures have recently garnered significant attention as photothermal transduction agents due to their facile preparation and favorable photothermal properties. In this study, we employed a coordinated approach involving Fe3+ and apigenin, a polyphenol compound, to construct the nanostructure (nFeAPG), with the assistance of ß-CD and DSPE-PEG facilitating the formation of the complex nanostructure. In vitro research demonstrated that the formed nFeAPG could induce cell death by elevating intracellular oxidative stress, inhibiting antioxidative system, and promoting apoptosis and ferroptosis, and near infrared spectrum irradiation further strengthen the therapeutic outcome. In 4T1 tumor bearing mice, nFeAPG could effectively accumulate into tumor site and exhibit commendable control over tumor growth. Futher analysis demonstrated that nFeAPG ameliorated the suppressed immune microenvironment by augmenting the response of DC cells and T cells. This study underscores that nFeAPG encompasses a multifaceted capacity to combat TNBC, holding promise as a compelling therapeutic strategy for TNBC treatment.

Bilirubin ameliorates osteoarthritis via activating Nrf2/HO-1 pathway and suppressing NF-κB signalling.

Osteoarthritis (OA) is a chronic degenerative joint disease that affects worldwide. Oxidative stress plays a critical role in the chronic inflammation and OA progression. Scavenging overproduced reactive oxygen species (ROS) could be rational strategy for OA treatment. Bilirubin (BR) is a potent endogenous antioxidant that can scavenge various ROS and also exhibit anti-inflammatory effects. However, whether BR could exert protection on chondrocytes for OA treatment has not yet been elucidated. Here, chondrocytes were exposed to hydrogen peroxide with or without BR treatment. The cell viability was assessed, and the intracellular ROS, inflammation cytokines were monitored to indicate the state of chondrocytes. In addition, BR was also tested on LPS-treated Raw264.7 cells to test the anti-inflammation property. An in vitro bimimic OA microenvironment was constructed by LPS-treated Raw264.7 and chondrocytes, and BR also exert certain protection for chondrocytes by activating Nrf2/HO-1 pathway and suppressing NF-κB signalling. An ACLT-induced OA model was constructed to test the in vivo therapeutic efficacy of BR. Compared to the clinical used HA, BR significantly reduced cartilage degeneration and delayed OA progression. Overall, our data shows that BR has a protective effect on chondrocytes and can delay OA progression caused by oxidative stress.

[Mechanism of n-butanol fraction of Wenxia Formula combining with gefitinib in treating non-small cell lung cancer based on network pharmacology and in vitro experiment].

This study combined network pharmacology, molecular docking, and in vitro experiments to explore the potential mechanism of the active components of the n-butanol fraction of Wenxia Formula(NWXF) combined with gefitinib(GEF) in treating non-small cell lung cancer(NSCLC). Ultra-performance liquid chromatography-quadrupole Orbitrap mass spectrometry(UPLC-Q-Orbitrap MS) was employed to detect the main chemical components of NWXF. The active components of NWXF were retrieved from SwissADME, and the candidate targets of these active components were retrieved from SwissTargetPrediction. Online Mendelian Inheritance in Man(OMIM) and GeneCards were searched for the targets of NSCLC. Cytoscape 3.9.0 and STRING were employed to build the protein-protein interaction(PPI) network with the common targets shared by NWXF and NSCLC. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment were performed in DAVID to predict the potential mechanisms. Finally, molecular docking between the main active ingredients and key targets was conducted in SYBYL-X 2.0. The methyl thiazolyl tetrazolium(MTT) assay was employed to evaluate the inhibitory effects of NWXF and/or GEF on the proliferation of human non-small cell lung cancer cells(A549 and PC-9). Additionally, the impact of NWXF on human embryonic lung fibroblast cells(MRC-5) was assessed. The effectiveness of the drug combination was evaluated based on the Q value. The terminal-deoxynucleoitidyl transferase mediated nick-end labeling(TUNEL) assay was employed to examine the apoptosis of A549 and PC-9 cells treated with NWXF and/or GEF. Quantitative real-time PCR(qRT-PCR) was employed to measure the mRNA levels of epidermal growth factor receptor(EGFR), c-Jun N-terminal kinase(JNK), and Bcl2-associated X protein(Bax) in the A549 and PC-9 cells treated with NWXF and/or GEF. Western blot was employed to determine the protein levels of EGFR, p-EGFR, JNK, p-JNK, and Bax in the A549 and PC-9 cells treated with NWXF and/or GEF. A total of 77 active components, 488 potential targets, and 49 key targets involved in the treatment of NSCLC with NWXF were predicted. The results of GO annotation showed that NWXF may treat NSCLC by regulating the biological processes such as cell proliferation, apoptosis, and protein phosphorylation. KEGG enrichment revealed that the key targets of NWXF in treating NSCLC were enriched in the mitogen-activated protein kinase(MAPK), phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT), hypoxia-inducible factor-1(HIF-1), and microRNA-related signaling pathways. Molecular docking results showed that 91.9% of the docking scores were greater than 5, indicating the strong binding capability between main active components and key targets. The cell experiments demonstrated that NWXF combined with GEF synergistically inhibited the proliferation, promoted the apoptosis, decreased p-EGFR/EGFR and p-JNK/JNK values, down-regulated the mRNA levels of EGFR and JNK, and up-regulated the mRNA and protein levels of Bax in A549 and PC-9 cells. In conclusion, NWXF combined with GEF can regulate the EGFR/JNK pathway to promote the apoptosis of NSCLC cells, thus treating NSCLC.

Preparation and Characterization of Perfluoropolyether-Silane@Ethye Cellulose Polymeric Microcapsules.

A novel polymeric microcapsule was designed and synthesized using perfluoropolyether silane (PFPE-silane) as a superhydrophobic core material and ethyl cellulose (EC) as a shell material. The effects of the stirring rate and the core-to-shell ratio on the synthesized microcapsules were investigated. The physicochemical properties of the polymeric microcapsules were evaluated using scanning electron microscopy, fourier transform infrared spectroscopy, thermogravimetric analysis, laser particle size analysis, and wettability analysis. The results showed that when the stirring rate was 650 rpm and the core-to-shell ratio was 1:1, well-distributed and uniformly dispersed microcapsules could be obtained. The results also indicated that the prepared polymeric microcapsules were spherical particles with micropores on the surface, and they had an average particle size of 165.71 µm. The EC shells could effectively prevent the thermal decomposition of PFPE-silane during cement hydration, and the PFPE-silane also exhibited excellent hydrophobicity. The specially designed structure of this polymeric microcapsule suggests its potential for enhancing the corrosion resistance of reinforced concrete structures.

Scalable Face Image Coding via StyleGAN Prior: Toward Compression for Human-Machine Collaborative Vision.

The accelerated proliferation of visual content and the rapid development of machine vision technologies bring significant challenges in delivering visual data on a gigantic scale, which shall be effectively represented to satisfy both human and machine requirements. In this work, we investigate how hierarchical representations derived from the advanced generative prior facilitate constructing an efficient scalable coding paradigm for human-machine collaborative vision. Our key insight is that by exploiting the StyleGAN prior, we can learn three-layered representations encoding hierarchical semantics, which are elaborately designed into the basic, middle, and enhanced layers, supporting machine intelligence and human visual perception in a progressive fashion. With the aim of achieving efficient compression, we propose the layer-wise scalable entropy transformer to reduce the redundancy between layers. Based on the multi-task scalable rate-distortion objective, the proposed scheme is jointly optimized to achieve optimal machine analysis performance, human perception experience, and compression ratio. We validate the proposed paradigm's feasibility in face image compression. Extensive qualitative and quantitative experimental results demonstrate the superiority of the proposed paradigm over the latest compression standard Versatile Video Coding (VVC) in terms of both machine analysis as well as human perception at extremely low bitrates (< 0.01 bpp), offering new insights for human-machine collaborative compression.

Identification of QTNs, QTN-by-environment interactions for plant height and ear height in maize multi-environment GWAS.

Plant height (PH) and ear height (EH) are important traits associated with biomass, lodging resistance, and grain yield in maize. There were strong effects of genotype x environment interaction (GEI) on plant height and ear height of maize. In this study, 203 maize inbred lines were grown at five locations across China's Spring and Summer corn belts, and plant height (PH) and ear height (EH) phenotype data were collected and grouped using GGE biplot. Five locations fell into two distinct groups (or mega environments) that coincide with two corn ecological zones called Summer Corn Belt and Spring Corn Belt. In total, 73,174 SNPs collected using GBS sequencing platform were used as genotype data and a recently released multi-environment GWAS software package IIIVmrMLM was employed to identify QTNs and QTN x environment (corn belt) interaction (QEIs); 12 and 11 statistically significant QEIs for PH and EH were detected respectively and their phenotypic effects were further partitioned into Add*E and Dom*E components. There were 28 and 25 corn-belt-specific QTNs for PH and EH identified, respectively. The result shows that there are a large number of genetic loci underlying the PH and EH GEIs and IIIVmrMLM is a powerful tool in discovering QTNs that have significant QTN-by-Environment interaction. PH and EH candidate genes were annotated based on transcriptomic analysis and haplotype analysis. EH related-QEI S10_135 (Zm00001d025947, saur76, small auxin up RNA76) and PH related-QEI S4_4 (Zm00001d049692, mads32, encoding MADS-transcription factor 32), and corn-belt specific QTNs including S10_4 (Zm00001d023333, sdg127, set domain gene127) and S7_1 (Zm00001d018614, GLR3.4, and glutamate receptor 3.4 or Zm00001d018616, DDRGK domain-containing protein) were reported, and the relationship among GEIs, QEIs and phenotypic plasticity and their biological and breeding implications were discussed.

Insight of the State for Deliberately Introduced A-Site Defect in Nanofibrous LaFeO3 for Boosting Artificial Photosynthesis of CH3OH.

Perovskite-type LaFeO3 is regarded as a potentially efficient visible-light photocatalyst owing to its narrow bandgap energy and unique photovoltaic properties. However, the insufficient active sites and the unsatisfactory utilization of photogenerated carriers severely restrict the realistic application of pure LaFeO3. Herein, we fabricated a series of LaxFeO3-δ nanofibers (x = 1.0, 0.95, 0.9, 0.85, 0.8) with an A-site defect via sol-gel combined with the electrospinning technique. Wherein, the nonstoichiometric La0.9FeO3-δ possessed the highest CH3OH yield of 5.30 µmol·g-1·h-1 with good chemical stability. A series of advanced characterizations were applied to investigate the physicochemical properties and charge-carrier behaviors of the samples. The results illustrated that the one-dimensional (1D) nanostructures combined with the appropriate concentration of vacancy defects on the surface contributed to the radial migration of photogenerated carriers, inhibited the recombination of carriers, and provided more CO2 adsorption-activation sites. Furthermore, density functional theory (DFT) calculations were employed to reveal the influence mechanism of vacancy defects on LaFeO3. This work provides a strategy to enhance the performance of photocatalytic CO2 reduction by modulating the induced oxygen vacancies caused by the A-site defect in perovskite oxides.

Identification of southern corn rust resistance QTNs in Chinese summer maize germplasm via multi-locus GWAS and post-GWAS analysis.

Southern corn rust (SCR) caused by Puccinia polysora Underw is a major disease leading to severe yield losses in China Summer Corn Belt. Using six multi-locus GWAS methods, we identified a set of SCR resistance QTNs from a diversity panel of 140 inbred lines collected from China Summer Corn Belt. Thirteen QTNs on chromosomes 1, 2, 4, 5, 6, and 8 were grouped into three types of allele effects and their associations with SCR phenotypes were verified by post-GWAS case-control sampling, allele/haplotype effect analysis. Relative resistance (RRR) and relative susceptibility (RRs) catering to its inbred carrier were estimated from single QTN and QTN-QTN combos and epistatitic effects were estimated for QTN-QTN combos. By transcriptomic annotation, a set of candidate genes were predicted to be involved in transcriptional regulation (S5_145, Zm00001d01613, transcription factor GTE4), phosphorylation (S8_123, Zm00001d010672, Pgk2- phosphoglycerate kinase 2), and temperature stress response (S6_164a/S6_164b, Zm00001d038806, hsp101, and S5_211, Zm00001d017978, cellulase25). The breeding implications of the above findings were discussed.

Ultraviolet B radiation-induced JPH203-loaded keratinocyte extracellular vesicles exert etiological interventions for psoriasis therapy.

Psoriasis is a multifactorial immuno-inflammatory skin disease, characterized by keratinocyte hyperproliferation and aberrant immune activation. Although the pathogenesis is complex, the interactions among inflammation, Th17-mediated immune activation, and keratinocyte hyperplasia are considered to play a crucial role in the occurrence and development of psoriasis. Therefore, pharmacological interventions on the "inflammation-Th17-keratinocyte" vicious cycle may be a potential strategy for psoriasis treatment. In this study, JPH203 (a specific inhibitor of LAT1, which engulfs leucine to activate mTOR signaling)-loaded, ultraviolet B (UVB) radiation-induced, keratinocyte-derived extracellular vesicles (J@EV) were prepared for psoriasis therapy. The EVs led to increased interleukin 1 receptor antagonist (IL-1RA) content due to UVB irradiation, therefore not only acting as a carrier for JPH203 but also functioning through inhibiting the IL-1-mediated inflammation cascade. J@EV effectively restrained the proliferation of inflamed keratinocytes via suppressing mTOR-signaling and NF-κB pathway in vitro. In an imiquimod-induced psoriatic model, J@EV significantly ameliorated the related symptoms as well as suppressed the over-activated immune reaction, evidenced by the decreased keratinocyte hyperplasia, Th17 expansion, and IL17 release. This study shows that J@EV exerts therapeutic efficacy for psoriasis by suppressing LAT1-mTOR involved keratinocyte hyperproliferation and Th17 expansion, as well as inhibiting IL-1-NF-κB mediated inflammation, representing a novel and promising strategy for psoriasis therapy.

Pontibacterium sinense sp. nov., a nitrate-reducing and thiosulphate-oxidizing bacterium, isolated from coastal sediment.

A novel bacterial strain, N1Y112T, was isolated from coastal sediment collected in Weihai, PR China. This Gram-stain-negative, facultatively anaerobic, motile rod-shaped bacterium exhibited the ability to oxidize thiosulphate to sulphate and reduce nitrate to ammonia through its Sox system and nitrate reduction pathway, respectively. The strain grew at 20-35 °C (optimum, 28 °C), pH 6.0-10.0 (optimum, pH 7.5) and in the presence of 1.0-5.0 % (w/v) NaCl (optimum, 3.0 %). Major fatty acids present in the strain included summed feature 8 (comprising C18 : 1 ω7c and/or C18 : 1 ω6c), summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c) and C16 : 0. Its polar lipid profile consisted of one phosphatidylethanolamine, two unknown aminolipids, one aminophosphoglycolipid, one diphosphatidylglycerol, one phosphatidylglycerol, two unknown phospholipids and two unknown lipids. Strain N1Y112T contained ubiquinone-7 and ubiquinone-8 as isoprenoid quinones, with a genomic G+C content of 50.6 mol%. Based on phylogenetic analysis, strain N1Y112T clustered with Pontibacterium granulatum JCM 30316T being its closest relative at 97.1 % 16S rRNA gene sequence similarity. The average nucleotide identity and digital DNA-DNA hybridization values were 77.1 and 20.7 %, respectively, which suggest significant differences between genomes of N1Y112T and P. granulatum JCM 30316T. Based on the findings from its phenotypic, genotypic and phylogenetic analyses, N1Y112T is considered to represent a novel species of the genus Pontibacterium, for which the name Pontibacterium sinense sp. nov. is proposed. The type strain is N1Y112T (=KCTC 72927T=MCCC 1H00429T).