Codelivery of TRAIL and Mitomycin C via Liposomes Shows Improved Antitumor Effect on TRAIL-Resistant Tumors.

Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) constitutes a promising antitumor drug, tumor resistance to TRAIL has become a major obstacle in its clinical application. Mitomycin C (MMC) is an effective TRAIL-resistant tumor sensitizer, which indicates a potential utility of combination therapy. However, the efficacy of this combination therapy is limited owing to its short half-life and the cumulative toxicity of MMC. To address these issues, we successfully developed a multifunctional liposome (MTLPs) with human TRAIL protein on the surface and MMC encapsulated in the internal aqueous phase to codeliver TRAIL and MMC. MTLPs are uniform spherical particles that exhibit efficient cellular uptake by HT-29 TRAIL-resistant tumor cells, thereby inducing a stronger killing effect compared with control groups. In vivo assays revealed that MTLPs efficiently accumulated in tumors and safely achieved 97.8% tumor suppression via the synergistic effect of TRAIL and MMC in an HT-29 tumor xenograft model while ensuring biosafety. These results suggest that the liposomal codelivery of TRAIL and MMC provides a novel approach to overcome TRAIL-resistant tumors.

Anticancer Effect of STING Agonist-Encapsulated Liposomes on Breast Cancer.

Breast cancer is one of the most common cancers worldwide, posing a serious threat to human health. Recently, innate immunity has become a widely discussed topic in antitumor research. The STING pathway is an important component of innate immunity, and several STING agonists have been developed and applied in antitumor research. Dimeric amidobenzimidazole (diABZI) is one STING agonist and is a nucleotide analog with low serological stability and cell membrane permeability. In this study, we prepared diABZI-encapsulated liposomes (dLNPs) using the ammonium sulfate gradient method. The average particle size of the dLNPs was 99.76 ± 0.230 nm, and the encapsulation efficiency was 58.29 ± 0.53%. Additionally, in vivo and in vitro assays showed that the dLNPs had a sustained-release effect and that the circulation time in vivo was longer than 48 h. The expression of IFN-ß and IFN-γ was elevated in mice treated with dLNPs. Moreover, we found that dLNPs can recruit CD8+ T cells to tumor tissue and exert antitumor effects. The dLNPs-treated group showed the most significant efficacy: the average tumor volume was 231.46 mm3, which decreased by 78.16% and 54.47% compared to the PBS group and diABZI group. Meanwhile, the hemolysis rate of the dLNPs was 2%, showing high biocompatibility. In conclusion, dLNPs can effectively suppress tumor growth and possess great potential in breast cancer therapy.

Liposome-Based Co-Immunotherapy with TLR Agonist and CD47-SIRPα Checkpoint Blockade for Efficient Treatment of Colon Cancer.

Antitumor immunity is an essential component of cancer therapy and is primarily mediated by the innate immune response, which plays a critical role in initiating and shaping the adaptive immune response. Emerging evidence has identified innate immune checkpoints and pattern recognition receptors, such as CD47 and Toll-like receptor 7 (TLR7), as promising therapeutic targets for cancer treatment. Based on the fusion protein Fc-CV1, which comprises a high-affinity SIRPα variant (CV1), and the Fc fragment of the human IgG1 antibody, we exploited a preparation which coupled Fc-CV1 to imiquimod (TLR7 agonist)-loaded liposomes (CILPs) to actively target CT26. WT syngeneic colon tumor models. In vitro studies revealed that CILPs exhibited superior sustained release properties and cell uptake efficiency compared to free imiquimod. In vivo assays proved that CILPs exhibited more efficient accumulation in tumors, and a more significant tumor suppression effect than the control groups. This immunotherapy preparation possessed the advantages of low doses and low toxicity. These results demonstrated that a combination of immune checkpoint blockade (ICB) therapy and innate immunity agonists, such as the Fc-CV1 and imiquimod-loaded liposome preparation utilized in this study, could represent a highly effective strategy for tumor therapy.

Deciphering soil resistance and virulence gene risks in conventional and organic farming systems.

Organic farming is a sustainable agricultural practice emphasizing natural inputs and ecological balance, and has garnered significant attention for its potential health and environmental benefits. However, a comprehensive evaluation of the emergent contaminants, particularly resistance and virulence genes within organic farming system, remains elusive. Here, a total of 36 soil samples from paired conventional and organic vegetable farms were collected from Jiangsu province, China. A systematic metagenomic approach was employed to investigate the prevalence, dispersal capability, pathogenic potential, and drivers of resistance and virulence genes across both organic and conventional systems. Our findings revealed a higher abundance of antibiotic resistance genes (ARGs), biocide resistance genes (BRGs), and virulence factor genes (VFGs) in organic farming system, with ARGs exhibiting a particularly notable increase of 10.76% compared to the conventional one. Pathogens such as Pseudomonas aeruginosa, Escherichia coli, and Mycobacterium tuberculosis were hosts carrying all four gene categories, highlighting their potential health implications. The neutral community model captured 77.1% and 71.9% of the variance in community dynamics within the conventional and organic farming systems, respectively, indicating that stochastic process was the predominant factor shaping gene communities. The relative smaller m value calculated in organic farming system (0.021 vs 0.023) indicated diminished gene exchange with external sources. Moreover, farming practices were observed to influence the resistance and virulence gene landscape by modifying soil properties, managing heavy metal stress, and steering mobile genetic elements (MGEs) dynamics. The study offers insights that can guide agricultural strategies to address potential health and ecological concerns.

Comparison of composting factors, heavy metal immobilization, and microbial activity after biochar or lime application in straw-manure composting.

Composting is an efficient way of disposing agricultural solid wastes as well as passivating heavy metals (HMs). Herein, equivalent (3%) biochar (BC) or lime (LM) were applied in rice straw and swine manure composting, with no additives applied as control group (CK). The results indicated that both the additives increased NO3--N content, organic matter degradation, humus formation, and HM immobilization in composting, and the overall improvement of lime was more significant. In addition, the additives optimized the bacterial community of compost, especially for thermophilic and mature phase. Lime stimulated the growth of Bacillus, Peptostreptococcus, Clostridium, Turicibacter, Clostridiaceae and Pseudomonas, which functioned well in HM passivation via biosorption, bioleaching, or promoting HM-humus formation by secreting hydrolases. Lime (3%) as additive is recommended in swine manure composting to promote composting maturity and reduce HM risk. The study present theoretical guidance in improving composting products quality for civil and industrial composting.

Effects of thermophiles inoculation on the efficiency and maturity of rice straw composting.

The present study investigated the effects of separately or simultaneously inoculating thermophilic fungus Aspergillus fumigatus Z5 and bacterium Geobacillus stearothermophilus B5 on lignocellulose degradation, enzyme activities and humification during rice straw composting. The results indicated that inoculation of Z5 accelerated the rise of temperature in the mesophilic phase, and the degradation degree of cellulose and hemicellulose was increased by 25.3% and 20.7%, respectively, due to the higher activities of lignocellulolytic enzymes. Inoculation of B5 increased 5-7 °C of the compost temperature in the thermophilic phase, and also prolonged the duration from 33 to 41 days. Inoculated simultaneously, the secreted hydrolases of Z5 generated more nutrition and promoted the growth of B5. B5 maintained and increased the compost temperature, thus presenting a better hydrolysis environment for extracellular hydrolases. Thermophilic inoculation altered the main physicochemical factors and improved efficiency and maturity in rice straw composting.

Long-term fertilization lowers the alkaline phosphatase activity by impacting the phoD-harboring bacterial community in rice-winter wheat rotation system.

PhoD-harboring bacteria and the secreted alkaline phosphatases (ALP) are crucial in the regulation of soil phosphorus (P) cycling. However, the influential factors of these crucial indicators and their internal interactions remain controversial. Here, a long-term field experiment containing different fertilization regimes was conducted (chemical, organic, and no fertilizer applied). The results indicated that the richness and diversity of phoD-harboring bacterial community were significantly decreased after long-term fertilization. The applied fertilizer promoted the growth of competitive species, while phoD-harboring bacteria lost the advantage to outcompete other microorganisms after long-term fertilization. The decreased ALP activity was caused by the declined phoD gene abundance, which is attributed to the comprehensive effects of soil organic C (SOC), total nitrogen (TN), and various forms of P. The random forest models identified SOC, TN, and available P (AP) to be the dominant environmental factors in shaping the phoD-harboring bacterial community. In addition, some other forms of P such as organic P (Po), inorganic P (Pi) or total P (TP) also exerted significant effects. Different fertilization regimes changed the keystone genera that contributed significantly to soil ALP activities, while Pseudolabrys and Pseudomonas were predicted to be the most important genera regardless of different fertilization regimes. This study extends the understanding of the main process and mechanisms of P mobilization in response to different fertilization regimes.

Laparoscopic simultaneous resection of bilateral giant primary mature retroperitoneal teratoma of the adrenal region: A case report.

RATIONALE: Giant mature retroperitoneal teratoma of the adrenal region is quite rare in adults. In most cases, open adrenalectomy is required to ensure complete resection. We describe a case of bilateral giant primary mature cystic teratoma in the region of both adrenal glands in a 22-year-old female patient. PATIENT CONCERNS: A 22-year-old female patient was admitted to our hospital with no complain after detecting to have 2 giant well circumscribed masses in a routine investigation. DIAGNOSES: She was diagnosed with bilateral giant primary mature retroperitoneal teratoma of the adrenal region. INTERVENTIONS: The patient underwent en bloc excision of the mass through laparoscopic simultaneous resection. OUTCOMES: We carefully separated and retained most of the adrenal tissue on both sides during surgery. Pathology reported mature teratomas. Eleven days after operation, the patient made uneventful recovery and left the hospital without any complication. LESSONS: Preoperative imaging and histologic analysis confirmed mature retroperitoneal teratomas. It is feasible to treat such giant benign tumors by laparoscopic simultaneous resection.

Effects of Lubricant and Toughening Agent on the Fluidity and Toughness of Poplar Powder-Reinforced Polylactic Acid 3D Printing Materials.

Three dimensional (3D) printing materials were manufactured with polylactic acid (PLA) and poplar powder using the twin screw extruder and 3D printing consumables extruder. Lubricant (TPW604) and toughening agent polyolefin elastomer (POE) were utilized to improve the fluidity and toughness of the materials. 3D printing materials were tested by infrared spectroscopy, X-ray diffraction, melt flow rate, rheology behavior, impact and scanning electron microscope. The results show that the poplar powder could decrease impact strength of PLA, the same as TPW604. Unlike poplar powder, TPW604 can improve the fluidity of 3D printing materials. And POE can fill the voids formed by poplar powder in PLA, enhance interface compatibility between poplar powder and PLA, and effectively improve the fluidity and impact strength of 3D printing materials.

Structure-based virtual screening of novel inhibitors of the uridyltransferase activity of Xanthomonas oryzae pv. oryzae GlmU.

N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) catalyzes the formation of UDP-GlcNAc, a fundamental precursor in cell wall biosynthesis. GlmU represents an attractive target for new antibacterial agents. In this study, a theoretical three-dimensional (3D) structure of GlmU from Xanthomonas oryzae pv. oryzae (Xo-GlmU) was generated, and the ligand-receptor interaction was investigated by molecular docking. Then a structure-based virtual screening was performed, three hit compounds were identified as specific inhibitors of the uridyltransferase activity of Xo-GlmU, with IC(50) values in the 0.81-23.21 µM range. Subsequently, the mode-of-inhibition and K(i) values of the three inhibitors were confirmed. The minimum inhibitory concentrations (MICs) of the candidate compounds for X. oryzae pv. oryzae (Xoo) were also determined. The research provided novel chemical scaffolds for antimicrobial drug discovery.

Treatment of alveolar cleft with distraction osteogenesis using anchorage with a tooth-microimplant joint in a dog model.

Our aim was to investigate the efficacy of correction of an alveolar cleft with distraction osteogenesis using anchorage with a tooth-microimplant joint in a canine model, which was established in 12 adult mongrel dogs that were subsequently randomised into two groups (n=6 in each). The first group comprised dogs that had osteogenesis using anchorage with a tooth (tooth group), while in the second, anchorage with tooth-microimplant joint (microimplant group) was used. All animals were killed one month after completion of distraction. Samples were collected for gross observation and histological examination. There was a significant difference in the degree of movement of the anchorage teeth in the transport discs between the 2 groups (p<0.01). There was less prominent inclination and shift of the natural teeth in the transport disc and less bony resorption around the root in the microimplant group than in the tooth group. These changes were less remarkable in the microimplant group. Treatment of alveolar cleft by distraction osteogenesis using anchorage with a tooth-microimplant joint is practical, and yields better results.