Relief effect of biochar on continuous cropping of tobacco through the reduction of p-hydroxybenzoic acid in soil.

Biochar application to soil has proven to be an excellent approach for decreasing the concentration of auto-toxic compounds and promoting plant growth in continuous-cropping fields. However, the mechanisms underlying the action pathway among biochars, auto-toxic compounds and tobacco remain unknown. In this study, we conducted an experiment tracking the incidence rate of black rot and auto-toxic compounds for a 3-year continuous-cropping tobacco pot trial in response to biochar treatment intensity compared with that of non-biochar treatment. Biochar inhibited the incidence of black rot. Using ultra-high-performance liquid chromatography-mass spectrometry (UPLC‒MS/MS), we revealed that biochar can effectively decrease the concentration of p-hydroxybenzoic acid (PHA), which is associated with the incidence rate of black rot (R2 = 0.890, p < 0.05). The sorption kinetics and isotherm of PHA sorption on biochar indicate that the coexistence of heterogeneous and monolayer sorption plays an important role in the adsorption process. Using Molecular dynamics (MD), Density functional theory (DFT) and Independent gradient model (IGM) analyses, we provide evidence that van der Waals force (vdW), π-π bonds and H-bonds between biochar and PHAs are the dominant factors that affect adsorption capacity. Moreover, the molecular adsorption rate (Nbiochar: NPHAs = 1:4) was theoretically calculated. In contrast, biochar dramatically increased nutrient retention capacity and improved soil properties, further enhancing tobacco quality, including its agronomic and physiological traits. Therefore, we considered that biochar not only relieved continuous cropping but also improved soil properties suitable for tobacco growth. Together, we demonstrate that the action of biochar in continuously cropped soil improves soil traits and alleviates auto-toxic compound toxicity. These data contribute to the direction of modified biochar application to improve continuous-cropping soil.

Activating transcription factor 6 contributes to cisplatin­induced ototoxicity via regulating the unfolded proteins response.

As a broad-spectrum anticancer drug, cisplatin is widely used in the treatment of tumors in various systems. Unfortunately, several serious side effects of cisplatin limit its clinical application, the most common of which are nephrotoxicity and ototoxicity. Studies have shown that cochlear hair cell degeneration is the main cause of cisplatin-induced hearing loss. However, the mechanism of cisplatin-induced hair cell death remains unclear. The present study aimed to explore the potential role of activating transcription factor 6 (ATF6), an endoplasmic reticulum (ER)-localized protein, on cisplatin-induced ototoxicity in vivo and in vitro. In this study, we observed that cisplatin exposure induced apoptosis of mouse auditory OC-1 cells, accompanied by a significant increase in the expression of ATF6 and C/EBP homologous protein (CHOP). In cell or cochlear culture models, treatment with an ATF6 agonist, an ER homeostasis regulator, significantly ameliorated cisplatin-induced cytotoxicity. Further, our in vivo experiments showed that subcutaneous injection of an ATF6 agonist almost completely prevented outer hair cell loss and significantly alleviated cisplatin-induced auditory brainstem response (ABR) threshold elevation in mice. Collectively, our results revealed the underlying mechanism by which activation of ATF6 significantly improved cisplatin-induced hair cell apoptosis, at least in part by inhibiting apoptosis signal-regulating kinase 1 expression, and demonstrated that pharmacological activation of ATF6-mediated unfolded protein response is a potential treatment for cisplatin-induced ototoxicity.

Harvesting Vibration Energy for Efficient Cocatalyst-Free Sonocatalytic H2 Production over Magnetically Separable Ultra-Low-Cost Fe3O4.

The cavitation effect is an important geochemical phenomenon, which generally exists under strong hydrodynamic conditions. Therefore, developing an economical and effective sonocatalyst becomes a vital method in capitalizing on the cavitation effect for energy generation. In this study, we first report a novel Fe3O4 sonocatalyst that can be easily separated using a magnetic field and does not require any additional cocatalysts for H2 production from H2O. When subjected to ultrasonic vibration, this catalyst achieves an impressive H2 production rate of up to 175 µmol/h/USD (where USD stands for dollars), surpassing most previously reported mechanical catalytic materials. Furthermore, the ease and efficiency of separating this catalyst using an external magnetic field, coupled with its effortless recovery, highlight its significant potential for practical applications. By addressing the key limitations of conventional sonocatalysts, our study not only demonstrates the feasibility of using Fe3O4 as a highly efficient sonocatalyst but also showcases the exciting possibility of using a new class of magnetically separable sonocatalysts to productively transform mechanical energy into chemical energy.

Effects of bone marrow mesenchymal stem cell-conditioned medium on the proliferation and migration of liposarcoma cells.

INTRODUCTION: Liposarcoma constitutes a prevalent subtype of soft tissue sarcoma, represents approximately 20% of all sarcomas. However, conventional chemotherapeutic agents have shown restricted effectiveness in treating liposarcoma patients. Accumulating evidence indicates that mesenchymal stem cells (MSCs) have the characteristic of migration to tumor site, promote or suppress tumors. How human bone marrow mesenchymal stem cells (BMSCs) contribute to liposarcoma phenotype remains poorly understood. This study aims to investigate the effects of human bone marrow mesenchymal stem cell-conditioned medium (BMSC-CM) on the proliferation and migration of liposarcoma cell lines 93T449 and SW872, as well as explore potential underlying mechanisms of BMSC-CM action on these cells. MATERIALS AND METHODS: We transfected BMSCs with lentiviral constructs to knock down the transcriptional co-activator Yes-associated protein 1 (YAP1), conditioned medium (CM) obtained from BMSCs and shYAP1-BMSC, respectively. Liposarcoma cell lines 93T449 and SW872 were co-cultured with BMSC-CM or shYAP1-BMSC-CM. Cell proliferation ability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was evaluated using flow cytometric assay. A wound healing assay was used to analyze cell migration. The expression levels of YAP1, Bcl-2, and matrix metalloproteinase-2 (MMP-2) were determined by western blot assay. RESULTS: Co-culturing liposarcoma cell lines 93T449 and SW872 with BMSC-CM promoted tumor cell proliferation, while shYAP1-BMSC-CM significantly inhibited cell viability and migration, induced apoptosis, and downregulated Bcl-2 and MMP-2 expression. CONCLUSIONS: These findings provide new insights into the impact of BMSC-CM on liposarcoma and suggest its possible involvement in liposarcoma cell growth.

Olfactory ensheathing cells as candidate cells for chronic pain treatment.

Chronic pain is often accompanied by tissue damage and pain hypersensitivity. It easily relapses and is challenging to cure, which seriously affects the patients' quality of life and is an urgent problem to be solved. Current treatment methods primarily rely on morphine drugs, which do not address the underlying nerve injury and may cause adverse reactions. Therefore, in recent years, scientists have shifted their focus from chronic pain treatment to cell transplantation. This review describes the classification and mechanism of chronic pain through the introduction of the characteristics of olfactory ensheathing cells (OECs), an in-depth discussion of special glial cells through the phagocytosis of nerve debris, receptor-ligand interactions, providing nutrition, and other inhibition of neuroinflammation, and ultimately supporting axon regeneration and mitigation of chronic pain. This review summarizes the potential and limitations of OECs for treating chronic pain by objectively analyzing relevant clinical trials and methods to enhance efficacy and future development prospects.

Defect Engineered Microcrystalline Cellulose for Enhanced Cocatalyst-Free Piezo-Catalytic H2 Production.

Mechanical energy driven piezocatalytic hydrogen (H2 ) production is a promising way to solve the energy crisis . But limited by the slow separation and transfer efficiency of piezoelectric charges generated on the surface of piezocatalysts , the piezocatalytic performance is still not satisfactory. Here, defect engineering is first used to optimize the piezocatalytic performance of microcrystalline cellulose (MCC). The piezocatalytic H2 production rate of MCC with the optimal defect concentration can reach up to 84.47 µmol g-1 h-1 under ultrasonic vibration without any co-catalyst, which is ≈3.74 times higher than that of the pure MCC (22.65 µmol g-1 h-1 ). The enhanced H2 production rate by piezoelectric catalysis is mainly due to the introduction of defect engineering on MCC, which disorders the symmetry of MCC crystal structure, improves the electrical conductivity of the material, and accelerates the separation and transfer efficiency of piezoelectric charges. Moreover, the piezocatalytic H2 production rate of MCC with the optimal defect concentration can still reach up to 93.61 µmol g-1 h-1 in natural seawater, showingits commendable practicability. This study presents a novel view for designing marvelous-performance biomass piezocatalysts through defect engineering, which can efficiently convert mechanical energy into chemical energy .

Partially brain effects of injection of human umbilical cord mesenchymal stem cells at injury sites in a mouse model of thoracic spinal cord contusion.

Purpose: The pain caused by spinal cord injury (SCI) poses a major burden on patients, and pain management is becoming a focus of treatment. Few reports have described changes in the brain after SCI. Particularly, the exact mechanism through which brain regions affect post-injury pain remains unclear. In this study, we aimed to determine the potential therapeutic mechanisms of pain. A mouse model of spinal cord contusion was established, and molecular expression in the anterior cingulate cortex (ACC) and periaqueductal gray (PAG) in the brain and animal behavior was observed after local injection of human umbilical cord mesenchymal stem cells (HU-MSCs) at the site of SCI. Method: Sixty-three female C57BL/6J mice were divided into four groups: a sham operation group (n = 15); a spinal injury group (SCI, n = 16); an SCI + HU-MSCs group (n = 16) and an SCI + PBS group (n = 16), in which the SCI site was injected with HU-MSCs/phosphate buffer. The BMS score was determined, and the von Frey test and Hargreaves test were used to assess behavior every week after surgery. Mice were sacrificed in the fourth week after operation, and samples were collected. The expression of CGRP, Substance P, C-Fos and KCC2 in the ACC and PAG were observed with immunohistochemistry. Chromic cyanine staining was used to observe transverse sections of the injured spinal cord. Result: In the ACC and PAG after SCI, the expression of CGRP, SP and C-Fos increased, and the expression of KCC2 decreased, whereas after HU-MSC injection, the expression of CGRP, SP and C-Fos decreased, and the expression of KCC2 increased. The SCI + HU-MSC group showed better exercise ability from 2 to 4 weeks after surgery than the SCI/SCI + PBS groups (P < 0.001). Local injection of HU-MSCs significantly improved the mechanical hyperalgesia caused by SCI in the fourth week after surgery (P < 0.0001), and sensation was significantly recovered 2 weeks after surgery (P < 0.0001); no improvement in thermal hypersensitivity was observed (P > 0.05). The HU-MSC group retained more white matter than the SCI/SCI + PBS groups (P < 0.0001). Conclusion: Local transplantation of HU-MSCs at the site of SCI partially relieves the neuropathic pain and promotes recovery of motor function. These findings suggest a feasible direction for the future treatment of SCI.

Heterojunction construction by a coordination bond between metal-organic frameworks and CdIn2S4 for improved photocatalytic performance.

Photocatalytic water splitting using a semiconductor is one of the most effective ways to obtain clean energy. However, a pure semiconductor exhibits a poor photocatalytic performance because of its harsh charge carrier recombination, limited light harvesting ability and deficiency of surface reactive sites. Herein, the hydrothermal method is employed to synthesize a new UiO-66-NH2/CdIn2S4 (NU66/CIS) heterojunction nanocomposite, constructed via a coordination bond between NU66 and CIS. Benefitting from the great specific surface area, the UiO-66-NH2 provides abundant reactive sites on its surface to boost the water reduction. Moreover, the amino groups in the UiO-66-NH2 are supplied as coordination sites to establish strong interactions between NU66 and CIS, thus forming the heterojunction with intimate connections. Therefore, the electrons produced by photoexcitation of CIS can be more effectively promoted to transfer to NU66, and then react with H+ in water to produce H2. Accordingly, the optimized 8% NU66/CIS heterojunction exhibits a considerable photocatalytic efficiency for water splitting, in which the H2 production rate is 7.8 times higher than that of bare CIS, and 3.5 times as high as that of the two materials combined by simple physical mixing. This research offers a creative and innovative idea for the construction of active MOF-based photocatalysts for H2 evolution.

Recent Advances in Biomaterials-Based Therapies for Alleviation and Regeneration of Traumatic Brain Injury.

Traumatic brain injury (TBI), a major public health problem accompanied with numerous complications, usually leads to serve disability and huge financial burden. The adverse and unfavorable pathological environment triggers a series of secondary injuries, resulting in serious loss of nerve function and huge obstacle of endogenous nerve regeneration. With the advances in adaptive tissue regeneration biomaterials, regulation of detrimental microenvironment to reduce the secondary injury and to promote the neurogenesis becomes possible. The adaptive biomaterials could respond and regulate biochemical, cellular, and physiological events in the secondary injury, including excitotoxicity, oxidative stress, and neuroinflammation, to rebuild circumstances suitable for regeneration. In this review, the development of pathology after TBI is discussed, followed by the introduction of adaptive biomaterials based on various pathological characteristics. The adaptive biomaterials carried with neurotrophic factors and stem cells for TBI treatment are then summarized. Finally, the current drawbacks and future perspective of biomaterials for TBI treatment are suggested.

Fault Early Warning Model for High-Speed Railway Train Based on Feature Contribution and Causal Inference.

The demands for model accuracy and computing efficiency in fault warning scenarios are increasing as high-speed railway train technology continues to advance. The black box model is difficult to interpret, making it impossible for this technology to be widely adopted in the railway industry, which has strict safety regulations. This paper proposes a fault early warning machine learning model based on feature contribution and causal inference. First, the contributions of the features are calculated through the Shapley additive explanations model. Then, causal relationships are discovered through causal inference models. Finally, data from causal and high-contribution time series are applied to the model. Ablation tests are conducted with the Naïve Bayes, Gradient Boosting Decision Tree, eXtreme Gradient Boosting, and other models in order to confirm the efficiency of the method based on early warning data regarding the on-site high-speed train traction equipment circuit board failure. The findings indicate that the strategy improves the evaluation markers, including the early warning accuracy, precision, recall, and F1 score, by an average of more than 10%. There is a 35% improvement in the computing efficiency, and the model can provide feature causal graph verification for expert product decision-making.

Label Noise Learning Method for Metallographic Image Recognition of Heat-Resistant Steel for Use in Pressure Equipment.

In metallographic examination, spherular pearlite gradation, an important step in a metallographic examination, is the main indicator used to assess the reliability of heat-resistant steel. Recognition of pearlite spheroidization via the manual way mainly depends on the subjective perceptions and experience of each inspector. Deep learning-based methods can eliminate the effects of the subjective factors that affect manual recognition. However, images with incorrect labels, known as noisy images, challenge successful application of image recognition of deep learning models to spherular pearlite gradation. A deep-learning-based label noise method for metallographic image recognition is thus proposed to solve this problem. We use a filtering process to pretreat the raw datasets and append a retraining process for deep learning models. The presented method was applied to image recognition for spherular pearlite gradation on a metallographic image dataset which contains 422 images. Meanwhile, three classic deep learning models were also used for image recognition, individually and coupled with the proposed method. Results showed that accuracy of image recognition by a deep learning model solely is lower than the one coupled with our method. Particularly, accuracy of ResNet18 was improved from 72.27% to 77.01%.

Detection and phylogenetic analysis of tick-borne bacterial and protozoan pathogens in a forest province of eastern China.

Ticks, as obligate blood-sucking ectoparasites, feed on a broad range of vertebrates and transmit a great diversity of pathogenic microorganisms. Some tick-borne pathogens (TBPs) are endemic in China, whereas epidemiological studies are limited in Jiangxi, a forest province located in eastern China. Here, we have determined the positivity rates of TBPs in humans, rodents, dogs, goats and ticks, and performed the molecular characterization of TBPs in Jiangxi province. We found a high positivity rate of TBPs in the collected samples, demonstrating 23 (12.92%) samples positive for more than one TBPs. Of those, 11 (6.18%) samples were positive for Rickettsia spp., six (3.37%) Ehrlichia spp./Anaplasma spp., one (0.56%) Bartonella spp., two (1.12%) Borrelia spp., and five (2.81%) Babesia spp. The positivity rates of TBPs varied among ticks, animals, and humans as follow: goats (14/37, 37.84%), ticks (8/35, 22.86%), and dogs (1/11, 9.09%). Humans and rodents were negative for TBP presence. Phylogenetic analyses of these TBP sequences revealed the presence of Rickettsia japonica, Ehrlichia minasensis, and an unclassified Babesia spp. in goats, and Anaplasma phagocytophilum, Borrelia valaisiana, and an unclassified Bartonella spp. in ticks. Furthermore, R. japonica infection was exclusively found in goats with the positivity rate of 29.73%. Our study is the first report of R. japonica in goats around the world. These findings suggest high TBP positivity rates among goats, ticks, and dogs, and diverse TBPs in goats and ticks in the studied sites. Therefore, our results underscore the urgent need to assess TBP-tick-vertebrate-environment interactions and the risk of tick borne disease exposure in humans in the future.

Haemaphysalis longicornis calreticulin is not an effective molecular tool for tick bite diagnosis and disruption of tick infestations.

BACKGROUND: Tick calreticulin (CRT) is a calcium-binding protein secreted into the host during blood feeding. It has been used as a biomarker of tick exposure and has potential as an anti-tick vaccine, but there is no information about these uses for Haemaphysalis longicornis CRT (HlCRT). We synthesized recombinant H. longicornis CRT (rHlCRT) and evaluated its potential for tick bite diagnosis and for disrupting tick infestations. METHODS: The responses of mice and rabbits exposed to H. longicornis ticks were measured with ELISA to determine the antibody level against rHlCRT. To evaluate the effects of rHlCRT-induced anti-tick immunity, engorgement weight, tick engorgement index (TEI), feeding duration, ecdysis rate, and egg weight per engorged tick were compared between ticks fed on immunized and normal mice. RESULTS: Mean anti-tick CRT antibody levels in sera collected from mice at 1 and 15 days after primary tick exposure were not significantly different from the mean antibody levels in negative control mice that were not bitten by ticks (all P values > 0.05). No significant anti-HlCRT IgG responses developed in mice after second exposure to tick bites compared with the level of anti-HlCRT antibody response in negative control mice (all P values > 0.25). For rabbits, no significant differences in the antibody levels were observed in animals before challenge infestation and after tick exposures, and in animals after two tick exposures (all P values > 0.10). There were no significant differences in the body weight of ticks fed on immunized and normal mice (all P values > 0.15). No significant differences in TEI were observed between ticks fed on immunized mice and normal control mice (all P values > 0.50). There were no significant differences in feeding duration for female ticks, and feeding duration and ecdysis rate for nymphs in the experimental and control groups (all P values > 0.10 for feeding duration and P value = 0.19 for ecdysis rate). We did not observe a significant difference in egg weight per tick in the rHlCRT-immunized and the control groups (P = 0.88). CONCLUSIONS: HlCRT in H. longicornis tick saliva proteins appears to be nonimmunogenic to mammalian hosts like mice and rabbits. Vaccination with rHlCRT did not generate effective immunity against parthenogenetic and bisexual H. longicornis nymphs or female ticks. These results indicate that HlCRT is not a suitable molecular candidate for H. longicornis tick bite diagnosis and not effective for the disruption of tick infestations.

Severe Rhipicephalus sanguineus tick infestation in a home from rural area of Nanchang in China.

On October 13, 2021, a tick infestation occurred in a home in rural area of Nanchang city, China, and we were asked to inspect the tick infestation. Ticks were collected in the largest number on courtyard door jambs, followed by living room and bedroom door jambs. Ticks were identified morphologically as Rhipicephalus sanguineus adults. The 16S rRNA analysis effectively distinguished the ticks in this study from other Rhipicephalus species, including R. sanguineus south-east, temperate and tropical lineages and identified genetically as R. sanguineus south China lineage. Tick samples were subjected to conventional PCR analysis and detected negative for the presence of tick-borne pathogens. Our findings indicate that there was low transmission risk of tick-borne pathogens to humans in the tick-infested home. Further studies are needed to proactively investigate the tick species in Nanchang, and determine the presence of tick-borne pathogens for assessing their threat to human health in the region.

Silicon Nanoparticles Enhance Ginger Rhizomes Tolerance to Postharvest Deterioration and Resistance to Fusarium solani.

Postharvest deterioration of ginger rhizome caused by microorganisms or wound infections causes significant economic losses. Fusarium solani is one of the important causal agents of prevalent ginger disease soft rot across the world. The massive and continuous use of chemical fungicides in postharvest preservation pose risks to human health and produce environmental contamination. Hence, new alternative tools are required to reduce postharvest deterioration and extend the postharvest life of ginger. In this study, the use of silicon nanoparticles (SiNPs) on the storability of ginger rhizomes during postharvest storage and their resistance to Fusarium solani was investigated. The results showed that 50, 100, and 150 mg L-1 of SiNPs increased the firmness of the ginger rhizome during storage but decreased the decay severity, water loss, total color difference, and the reactive oxygen species (ROS; H2O2 and superoxide anion) accumulation. Specifically, 100 mg L-1 (SiNP100) demonstrated the best effect in the extension of postharvest life and improved the quality of the ginger rhizomes. SiNP100 application increased the activities of antioxidant enzymes (SOD and CAT) and the total phenolics and flavonoid contents, thereby reducing the ROS accumulation and malondialdehyde (MDA) content. Meanwhile, SiNP100 treatment negatively impacts the peroxidase (POD) and polyphenol oxidase (PPO) activities, which may have contributed to the lower level of lignin and decreased total color difference. SiNP100 likely decreased water loss and the transfer of water by altering the expression of aquaporin genes. Moreover, SiNP100 modulated the expression of lignin synthesis and phytopathogenic responses genes including MYB and LysM genes. Furthermore, SiNP100 inhibited Fusarium solani by preventing the penetration of hyphae into cells, thus decreasing the severity of postharvest pathogenic decay. In summary, this study revealed the physiology and molecular mechanisms of SiNPs-induced tolerance to postharvest deterioration and resistance to disease, which provides a foundation for using SiNPs resources as a promising alternative tool to maintain ginger quality and control postharvest diseases.

Quantitative Trait Locus Analysis and Identification of Candidate Genes for Micronaire in an Interspecific Backcross Inbred Line Population of Gossypium hirsutum × Gossypium barbadense.

Cotton is the most important fiber crop and provides indispensable natural fibers for the textile industry. Micronaire (MIC) is determined by fiber fineness and maturity and is an important component of fiber quality. Gossypium barbadense L. possesses long, strong and fine fibers, while upland cotton (Gossypium hirsutum L.) is high yielding with high MIC and widely cultivated worldwide. To identify quantitative trait loci (QTLs) and candidate genes for MIC in G. barbadense, a population of 250 backcross inbred lines (BILs), developed from an interspecific cross of upland cotton CRI36 × Egyptian cotton (G. barbadense) Hai7124, was evaluated in 9 replicated field tests. Based on a high-density genetic map with 7709 genotyping-by-sequencing (GBS)-based single-nucleotide polymorphism (SNP) markers, 25 MIC QTLs were identified, including 12 previously described QTLs and 13 new QTLs. Importantly, two stable MIC QTLs (qMIC-D03-2 on D03 and qMIC-D08-1 on D08) were identified. Of a total of 338 genes identified within the two QTL regions, eight candidate genes with differential expression between TM-1 and Hai7124 were identified. Our research provides valuable information for improving MIC in cotton breeding.

Research advances of biomaterials-based microenvironment-regulation therapies for repair and regeneration of spinal cord injury.

Traumatic spinal cord injury (SCI) usually results in restricted behaviour recovery and even life-changing paralysis, accompanied with numerous complications. Pathologically, the initial injuries trigger a series of secondary injuries, leading to an expansion of lesion site, a mass of neuron loss, and eventual failure of endogenous axon regeneration. As the advances rapidly spring up in regenerative medicine and tissue engineering biomaterials, regulation of these secondary injuries becomes possible, shedding a light on normal functional restoration. The successful tissue regeneration lies in proper regulation of the inflammatory microenvironment, including the inflammatory immune cells and inflammatory factors that lead to oxidative stress, inhibitory glial scar and neuroexcitatory toxicity. Specifically, the approaches based on microenvironment-regulating biomaterials have shown great promise in the repair and regeneration of SCI. In this review, the pathological inflammatory microenvironments of SCI are discussed, followed by the introduction of microenvironment-regulating biomaterials in terms of their impressive therapeutic effect in attenuation of secondary inflammation and promotion of axon regrowth. With the emphasis on regulating secondary events, the biomaterials for SCI treatment will become promising for clinical applications.

Optimization of the Administration Strategy for the Armed Oncolytic Adenovirus ZD55-IL-24 in Both Immunocompromised and Immunocompetent Mouse Models.

ZD55-IL-24 is an armed oncolytic adenovirus similar but superior to ONYX-015. Virotherapeutic strategies using ZD55-IL-24 have been demonstrated to be effective against several cancer types. However, it is unclear whether the traditional administration strategy is able to exert the maximal antitumor efficacy of ZD55-IL-24. In this study, we sought to optimize the administration strategy of ZD55-IL-24 in both A375-bearing immunocompromised mouse model and B16-bearing immunocompetent mouse model. Although the underlying antitumor mechanisms are quite different, the obtained results are similar in these two mouse tumor models. We find that the antitumor efficacy of ZD55-IL-24 increases as injection times increase in both of these two models. However, no obvious increase of efficacy is observed as the dose of each injection increases. Our further investigation reveals that the administration strategy of sustained ZD55-IL-24 therapy can achieve a better therapeutic effect than the traditional administration strategy of short-term ZD55-IL-24 therapy. Furthermore, there is no need to inject every day; every 2 or 3 days of injection achieves an equivalent therapeutic efficacy. Finally, we find that the sustained rather than the traditional short-term ZD55-IL-24 therapy can synergize with anti-PD-1 therapy to reject tumors in B16-bearing immunocompetent mouse model. These findings suggest that the past administration strategy of ZD55-IL-24 is in fact suboptimal and the antitumor efficacy can be further enhanced through administration strategy optimization. This study might shed some light on the development of clinically applicable administration regimens for ZD55-IL-24 therapy.

Enhanced anti-melanoma efficacy through a combination of the armed oncolytic adenovirus ZD55-IL-24 and immune checkpoint blockade in B16-bearing immunocompetent mouse model.

Although the recent treatment in melanoma through the use of anti-PD-1 immunotherapy is successful, the efficacy of this approach remains to be improved. Here, we explore the feasibility of combination strategy with the armed oncolytic adenovirus ZD55-IL-24 and PD-1 blockade. We find that combination therapy with localized ZD55-IL-24 and systemic PD-1 blockade leads to synergistic inhibition of both local and distant established tumors in B16-bearing immunocompetent mouse model. Our further mechanism investigation reveals that synergistic therapeutic effect is associated with marked promotion of tumor immune infiltration and recognition in both local and distant tumors as well as spleens. PD-1 blockade has no obvious effect on promotion of tumor immune infiltration and recognition. Localized therapy with ZD55-IL-24, however, can help PD-1 blockade to overcome the limitation of relatively low tumor immune infiltration and recognition. This study provides a rationale for investigation of such combination therapy in the clinic.

Structures and biological evaluation of phenylpropanoid derivatives from Dendrobium Sonia.

Two new phenylpropanoid derivatives (1-2), together with eight known compounds (3-10) were isolated from the stems of Dendrobium sonia. The structures of these compounds were elucidated on the basis of spectroscopic analyses, including HRESIMS, 1 D and 2 D NMR experiments. All of the isolated compounds were tested for their Nitric Oxide (NO) Inhibitory Activities. The results of bioactive screening showed that compounds 2, 8, 9 and 10 exerted inhibitory effects on NO production with IC50 values in the range of 26.3 to 31.6 µM. Compound 8 and 9 exhibited stronger anti-inflammatory activities with IC50 values 26.3 and 27.7 µM, comparable to that of the positive control.