NIR triggered polydopamine coated cerium dioxide nanozyme for ameliorating acute lung injury via enhanced ROS scavenging.

Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1ß and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.

Measurements of 131I activity in thyroid of workers at the place of radioiodine therapy in 38 hospitals in China.

To investigate the levels of 131I activity in thyroid of workers at the place of radioiodine therapy and their main influential factors in China, 341 workers at 38 hospitals performing radioiodine therapy procedure in five provinces were recruited to be measured in 2021. A hand-held gamma spectrometer with NaI(Tl) probe was plastered to the thyroids and thighs of the subjects during the measurement, and each measurement time was 120 s. The internal exposure dose was calculated, and the committed effective dose was estimated. In 86 (25.22%) of the 341 examined workers, 131I thyroid activity was above minimum detectable activity (MDA, 26.6 Bq). The maximum activity was 4.9 × 103 Bq. The detection results above MDA were at 22 (57.89%) different hospitals. The detectable rate for private hospitals (4.8%) was significantly lower than that for public hospitals (26.6%), P < 0.05. The detectable rate for hospitals in provincial capital cities (15.4%) was significantly lower than in nonprovincial capital cities (41.7%), P < 0.001. The detectable rate for hospitals engaged in 131I therapy for thyroid cancer (31.2%) was significantly higher than only for hyperthyroidism (10.3%), P < 0.001. A total of 32 subjects' committed effective dose might exceed 1 mSv. Results indicated the 131I activity in the thyroid of workers at the place of radioiodine varied considerably in China, and mainly related to ownership, location and therapy program of the hospitals.

A chromosome-level haplotype-resolved genome assembly of oriental tobacco budworm (Helicoverpa assulta).

Oriental tobacco budworm (Helicoverpa assulta) and cotton bollworm (Helicoverpa armigera) are two closely related species within the genus Helicoverpa. They have similar appearances and consistent damage patterns, often leading to confusion. However, the cotton bollworm is a typical polyphagous insect, while the oriental tobacco budworm belongs to the oligophagous insects. In this study, we used Nanopore, PacBio, and Illumina platforms to sequence the genome of H. assulta and used Hifiasm to create a haplotype-resolved draft genome. The Hi-C technique helped anchor 33 primary contigs to 32 chromosomes, including two sex chromosomes, Z and W. The final primary haploid genome assembly was approximately 415.19 Mb in length. BUSCO analysis revealed a high degree of completeness, with 99.0% gene coverage in this genome assembly. The repeat sequences constituted 38.39% of the genome assembly, and we annotated 17093 protein-coding genes. The high-quality genome assembly of the oriental tobacco budworm serves as a valuable genetic resource that enhances our comprehension of how they select hosts in a complex odour environment. It will also aid in developing an effective control policy.

Fine-Tuning Crystal Structures of Lead Bromide Perovskite Nanocrystals through Trace Cadmium(II) Doping for Efficient Color-Saturated Green LEDs.

Decreasing perovskite nanocrystal size increases radiative recombination due to the quantum confinement effect, but also increases the Auger recombination rate which leads to carrier imbalance in the emitting layers of electroluminescent devices. Here, we overcome this trade-off by increasing the exciton effective mass without affecting the size, which is realized through the trace Cd2+ doping of formamidinium lead bromide perovskite nanocrystals. We observe an ~2.7 times increase in the exciton binding energy benefiting from a slight distortion of the [BX6]4- octahedra caused by doping in the case of that the Auger recombination rate is almost unchanged. As a result, bright color-saturated green emitting perovskite nanocrystals with a photoluminescence quantum yield of 96 % are obtained. Cd2+ doping also shifts up the energy levels of the nanocrystals, relative to the Fermi level so that heavily n-doped emitters convert into only slightly n-doped ones; this boosts the charge injection efficiency of the corresponding light-emitting diodes. The light-emitting devices based on those nanocrystals reached a high external quantum efficiency of 29.4 % corresponding to a current efficiency of 123 cd A-1, and showed dramatically improved device lifetime, with a narrow bandwidth of 22 nm and Commission Internationale de I'Eclairage coordinates of (0.20, 0.76) for color-saturated green emission for the electroluminescence peak centered at 534 nm, thus being fully compliant with the latest standard for wide color gamut displays.

[Clinical Application of Microwave Ablation in Potentially Resectable Colorectal Cancer With Simultaneously Multiple Liver Metastases].

Objective To analyze the clinical efficacy of microwave ablation in the colorectal cancer with simultaneously multiple liver metastases that was initially evaluated as potentially resectable. Methods The patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases treated in the Department of General Surgery of the First Affiliated Hospital of Hebei North University,the Center of Minimally Invasive Therapy in Oncology of Traditional Chinese and Western Medicine in Dongzhimen Hospital of Beijing University of Chinese Medicine,and the Second Department of General Surgery in the Fourth Hospital of Hebei Medical University from October 1,2018 to October 1,2020 were selected in this study.The general data,pathological features,treatment methods,and clinical efficacy of the patients were collected.According to the treatment methods,the patients were assigned into a surgical resection group(conversion therapy+laparoscopic primary resection+hepatectomy)and a microwave ablation group(conversion therapy+laparoscopic primary resection+microwave ablation).The surgical indicators(operation duration,time to first postoperative anal exhaust,hospital stay,etc.)and postoperative complications(anastomotic stenosis,anastomotic hemorrhage,incision infection,etc.)were compared between the two groups.The survival period was followed up,including the overall survival period and disease-free survival period,and the survival curves were drawn to analyze the clinical efficacy of the two treatment regimens. Results A total of 198 patients with potentially resectable colorectal cancer with simultaneous multiple liver metastases were included in this study.Sixty-six patients were cured by neoadjuvant chemotherapy(FOLFOX or FOLFIRI),including 30 patients in the surgical resection group and 36 patients in the microwave ablation group(with 57 tumors ablated).After the first ablation,54(94.74%)tumors achieved complete ablation,and all of them reached no evidence of disease status after re-ablation.The microwave ablation group had shorter operation duration,less intraoperative blood loss,shorter time to first postoperative anal exhaust,shorter time of taking a liquid diet,shorter hospital stay,and lower hospitalization cost than the surgical resection group(all P<0.001).In addition,the microwave ablation group had lower visual analogue scale score(P<0.001)than the surgical resection group.The incidences of complications such as incision infection(P=0.740),anastomotic fistula(P=1.000),and anastomotic stenosis(P=1.000),the overall survival period(P=0.191),and the disease-free survival period(P=0.934)showed no significant differences between the two groups. Conclusions For patients with colorectal cancer with simultaneous multiple liver metastases initially assessed as potentially resectable,laparoscopic primary resection+surgical resection/microwave ablation after conversion therapy was safe,effective,and had similar survival outcomes.Microwave ablation outperformed surgical resection in postoperative recovery,economy,and tolerability,being worthy of clinical promotion.

Association of prognostic nutritional index with mortalities in American adult cancer survivors: A cohort study based on NHANES, 1999-2018.

The prognostic nutritional index (PNI) has been associated with disease progression and overall survival among cancer patients. Nonetheless, the association between PNI and mortality risk in adult cancer patients within the United States remains unexplored. This study aims to elucidate the connection between PNI and prognostic outcomes in American adult cancer patients. This cohort study derived data from the National Health and Nutrition Examination database, involving 4366 American adults diagnosed with cancer between 1999 and 2018. The nutritional status was assessed using the PNI, with higher PNI scores indicating a more favorable nutritional status. The study employed Kaplan-Meier curves and Cox proportional hazard regression to investigate the impact of PNI on various outcomes, including all-cause mortality (ACM), cardiovascular mortality (CAM), and malignancy tumor mortality (MTM) among adult cancer patients. Furthermore, restricted cubic spline models were used to examine the potential nonlinear relationship between the variables by creating hazard ratio (HR) curves at four specific points. The median follow-up duration was 84 months, during which 1530 (35.04%) cases of ACM occurred, including 331 (13.67%) CAM and 449 (10.45%) MTM. COX regression analysis revealed a significant inverse association between PNI and patient prognosis, with HRs of 0.95 (95% CI: 0.93-0.96, p < .001) for ACM, 0.93 (95% CI: 0.90-0.96, p < .001) for CAM, and 0.94 (95% CI: 0.91-0.97, p < .001) for MTM. Both Kaplan-Meier analyses and restricted cubic spline curves showed significant differences in mortality rates related to PNI (p < .001, nonlinear p < .001). Our study provides compelling evidence of a clear association between PNI and reduced risk of ACM, CAM, and MTM in adult cancer patients in the United States. These findings underscore the significance of incorporating PNI as a possible prognostic indicator for individuals diagnosed with cancer.

DNA methylation modulates epigenetic regulation in colorectal cancer diagnosis, prognosis and precision medicine.

Colorectal cancer (CRC) is a multifaceted disease influenced by the interplay of genetic and environmental factors. The clinical heterogeneity of CRC cannot be attributed exclusively to genetic diversity and environmental exposures, and epigenetic markers, especially DNA methylation, play a critical role as key molecular markers of cancer. This review compiles a comprehensive body of evidence underscoring the significant involvement of DNA methylation modifications in the pathogenesis of CRC. Moreover, this review explores the potential utility of DNA methylation in cancer diagnosis, prognostics, assessment of disease activity, and prediction of drug responses. Recognizing the impact of DNA methylation will enhance the ability to identify distinct CRC subtypes, paving the way for personalized treatment strategies and advancing precision medicine in the management of CRC.

Symptom clusters and nutritional status in primary liver cancer patients receiving TACE.

INTRODUCTION: symptom clusters (SCs) are highly prevalent among patients diagnosed with primary liver cancer. Malnutrition poses a heightened risk for a more pronounced total symptom cluster score. OBJECTIVE: this study aimed to identify SCs and assess the nutritional status of patients undergoing transcatheter arterial chemoembolization (TACE). Furthermore, it aimed to investigate the association between nutritional status and symptom clusters. METHODS: primary liver cancer patients who were scheduled to receive TACE were recruited. Symptoms data were collected using the MD Anderson Symptom Inventory (MDASI-C) and the Symptom Module specific to Primary Cancer (TSM-PLC). Nutritional assessment relied on the Nutritional Risk Screening-2002 (NRS-2002) and blood biochemistry. The SCs were extracted using exploratory factor analysis, while the relationship between SCs and nutritional status was evaluated using Spearman correlation analysis. RESULTS: the study included 226 patients, four distinct symptom clusters emerged: emotional-psychological symptom cluster, upper gastrointestinal symptom cluster, post-embolization-related symptom cluster, and liver function impairment symptom cluster. 68.14 % of patients were found to be at high risk of malnutrition. Our study revealed significant differences in Scs scores between patients at risk of malnutrition and those without such risk (p < 0.050). Notably, we observed a positive correlation between NRS-2002 scores and the scores of all symptom clusters (r = 0.205 to 0.419, p < 0.001), while a negative correlation was observed between prealbumin levels and the scores of all symptom clusters (r = -0.183 to -0.454, p < 0.001). CONCLUSION: the study highlights the high risk of malnutrition among liver cancer patients receiving TACE and the positive correlation between high malnutrition risk and Scs scores.

Genome-wide identification and analysis of WD40 proteins reveal that NtTTG1 enhances drought tolerance in tobacco (Nicotiana tabacum).

BACKGROUND: WD40 proteins, which are highly prevalent in eukaryotes, play important roles in plant development and stress responses. However, systematic identification and exploration of WD40 proteins in tobacco have not yet been conducted. RESULTS: In this study, a total of 399 WD40 regulatory genes were identified in common tobacco (Nicotiana tabacum). Gene structure and motif analysis revealed structural and functional diversity among different clades of tobacco WD40 regulatory genes. The expansion of tobacco WD40 regulatory genes was mainly driven by segmental duplication and purifying selection. A potential regulatory network of NtWD40s suggested that NtWD40s might be regulated by miRNAs and transcription factors in various biological processes. Expression pattern analysis via transcriptome analysis and qRT-PCR revealed that many NtWD40s exhibited tissue-specific expression patterns and might be involved in various biotic and abiotic stresses. Furthermore, we have validated the critical role of NtTTG1, which was located in the nuclei of trichome cells, in enhancing the drought tolerance of tobacco plants. CONCLUSIONS: Our study provides comprehensive information to better understand the evolution of WD40 regulatory genes and their roles in different stress responses in tobacco.

Effect of serum uric acid and gout on the incidence of colorectal cancer: A meta-analysis.

OBJECTIVE: Pathogenesis of colorectal cancer (CRC) depends on multiple factors. Identifying risk factors for CRC may facilitate the early prevention of the disease. We aimed to assess whether existing evidence suggests that serum uric acid (SUA) levels and gout are associated with CRC incidence. METHODS: The study was registered on PROSPERO (CRD42022371591). Searches of PubMed, Embase, and Cochrane Library were conducted from the establishment to November 11, 2022. Pooled relative risk (RR) with 95 % confidence intervals (CI) was derived to evaluate the effect of SUA or gout on CRC incidence. Non-linear trend analysis was conducted to explore the relationship between SUA level and CRC incidence. RESULTS: Twelve eligible studies with 22 reports were included. A meta-analysis of the included studies showed that when the highest and lowest SUA level categories were compared, an association between SUA level and CRC incidence was revealed (RR, 1.35; 95 % CI: 1.27-1.43; P < 0.001). Non-linear relationship between SUA level and CRC incidence was found. Further meta-analysis indicated that gout was associated with CRC incidence (RR, 1.22; 95 % CI: 1.08-1.36; P = 0.001). CONCLUSIONS: Both SUA level and gout were associated with an increased risk of CRC. Maintaining low SUA levels may be beneficial in reducing the incidence of CRC. Further studies evaluating the precise mechanisms underlying this association are needed to establish whether SUA/gout causes CRC.

Ailanthone synergizes with PARP1 inhibitor in tumour growth inhibition through crosstalk of DNA repair pathways in gastric cancer.

In our previous research, we proved that ailanthone (AIL) inhibits the growth of gastric cancer (GC) cells and causes apoptosis by inhibiting P23. However, we still find some GC organoids are insensitive to AIL. We have done some sequencing analysis and found that the insensitive strains are highly expressed in PARP1. In this study, we investigated whether AIL can enhance the anti-tumour effect of PARPi in GC. CCK8 and spheroid colony formation assay were used to measure anti-tumour effects. SynergyFinder software was used to calculate the synergy score of the drug combination and flow cytometry was used to detect apoptosis. Western blot, IHC, IF tests were used to measure protein expression. Finally, nude mouse xenograft models were used to verify the in vitro mechanisms. High expression of PARP1 was found to be the cause of drug insensitivity. When AIL is paired with a PARP1 inhibitor, olaparib (OLP), drug sensitivity improves. We discovered that this combination functions by blocking off HSP90-BRCA1 interaction and inhibiting the activity of PARP1, thus in turn inhibiting the homologous recombination deficiency and base excision repair pathway to finally achieve synthetic lethality through increased sensitivity. Moreover, P23 can regulate BRCA1 in GC in vitro. This study proves that the inhibitory effect of AIL on BRCA1 allowed even cancer cells with normal BRCA1 function to be sensitive to PARP inhibitors when it is simultaneously administered with OLP. The results greatly expanded the scope of the application of PARPi.

The egg ribonuclease SjCP1412 accelerates liver fibrosis caused by Schistosoma japonicum infection involving damage-associated molecular patterns (DAMPs).

Schistosomiasis, a parasite infectious disease caused by Schistosoma japonicum, often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released in the host liver. This study focuses on the role of the egg antigens CP1412 protein of S. japonicum (SjCP1412) with RNase activity in promoting liver fibrosis. In this study, the recombinant egg ribonuclease SjCP1412, which had RNase activity, was successfully prepared. By analysing the serum of the population, it has been proven that the anti-SjCP1412 IgG in the serum of patients with advanced schistosomiasis was moderately correlated with liver fibrosis, and SjCP1412 may be an important antigen associated with liver fibrosis in schistosomiasis. In vitro, the rSjCP1412 protein induced the human liver cancer cell line Hep G2 and liver sinusoidal endothelial cells apoptosis and necrosis and the release of proinflammatory damage-associated molecular patterns (DAMPs). In mice infected with schistosomes, rSjCP1412 immunization or antibody neutralization of SjCP1412 activity significantly reduced cell apoptosis and necroptosis in liver tissue, thereby reducing inflammation and liver fibrosis. In summary, the SjCP1412 protein plays a crucial role in promoting liver fibrosis during schistosomiasis through mediating the liver cells apoptosis and necroptosis to release DAMPs inducing an inflammatory reaction. Blocking SjCP1412 activity could inhibit its proapoptotic and necrotic effects and alleviate hepatic fibrosis. These findings suggest that SjCP1412 may be served as a promising drug target for managing liver fibrosis in schistosomiasis japonica.

Carbon nanosol-induced assemblage of a plant-beneficial microbiome consortium.

Carbon nanosol (CNS) is a carbon-based nanomaterial that promotes plant growth; however, its functional mechanisms and effects on the microbiome are not fully understood. Here, we explored the effects of CNS on the relationship between the soil, endophytic microbiomes and plant productivity. CNS treatment increased the fresh biomass of tobacco (Nicotiana tabacum L.) plants by 27.4% ± 9.9%. Amplicon sequencing analysis showed that the CNS treatment significantly affected the composition and diversity of the microbial communities in multiple ecological niches associated with tobacco, especially the bulk soil and stem endophytic microbiome. Furthermore, the application of CNS resulted in enhanced network connectivity and stability of the microbial communities in different niches, particularly in the soil, implying a strengthening of certain microbial interactions. Certain potentially growth-promoting root endophytic bacteria were more abundant under the CNS treatment. In addition, CNS increased the abundance of some endophytic microbial functional genes known to enhance plant growth, such as those associated with nutrient metabolism and the plant hormone biosynthesis pathways. We isolated two bacterial strains (Sphingopyxis sp. and Novosphingobium sp.) that were enriched under CNS treatment, and they were confirmed to promote tobacco plant growth in vitro. These results suggested that CNS might, at least in part, promote plant growth by enriching beneficial bacteria in the microbiome.

Identification of potentially functional circRNAs and prediction of the circRNA-miRNA-hub gene network in mice with primary blast lung injury.

OBJECTIVES: Primary blast lung injury (PBLI) is the main cause of death in blast injury patients, and is often ignored due to the absence of a specific diagnosis. Circular RNAs (circRNAs) are becoming recognized as new regulators of various diseases, but the role of circRNAs in PBLI remain largely unknown. This study aimed to investigate PBLI-related circRNAs and their probable roles as new regulators in PBLI in order to provide new ideas for PBLI diagnosis and treatment. METHODS: The differentially expressed (DE) circRNA and mRNA profiles were screened by transcriptome high-throughput sequencing and validated by quantitative real-time PCR (qRT-PCR). The GO and KEGG pathway enrichment was used to investigate the potential function of DE mRNAs. The interactions between proteins were analyzed using the STRING database and hub genes were identified using the MCODE plugin. Then, Cytoscape software was used to illustrate the circRNA-miRNA-hub gene network. RESULTS: A total of 117 circRNAs and 681 mRNAs were aberrantly expressed in PBLI, including 64 up-regulated and 53 down-regulated circRNAs, and 315 up-regulated and 366 down-regulated mRNAs. GO and KEGG analysis revealed that the DE mRNAs might be involved in the TNF signaling pathway and Fanconi anemia pathway. Hub genes, including Cenpf, Ndc80, Cdk1, Aurkb, Ttk, Aspm, Ccnb1, Kif11, Bub1 and Top2a, were obtained using the MCODE plugin. The network consist of 6 circRNAs (chr18:21008725-21020999 + , chr4:44893533-44895989 + , chr4:56899026-56910247-, chr5:123709382-123719528-, chr9:108528589-108544977 + and chr15:93452117-93465245 +), 7 miRNAs (mmu-miR-3058-5p, mmu-miR-3063-5p, mmu-miR-668-5p, mmu-miR-7038-3p, mmu-miR-761, mmu-miR-7673-5p and mmu-miR-9-5p) and 6 mRNAs (Aspm, Aurkb, Bub1, Cdk1, Cenpf and Top2a). CONCLUSIONS: This study examined a circRNA-miRNA-hub gene regulatory network associated with PBLI and explored the potential functions of circRNAs in the network for the first time. Six circRNAs in the circRNA-miRNA-hub gene regulatory network, including chr18:21008725-21020999 + , chr4:44893533-44895989 + , chr4:56899026-56910247-, chr5:123709382-123719528-, chr9:108528589-108544977 + and chr15:93452117-93465245 + may play an essential role in PBLI.

Isolation and Identification of Biocontrol Bacteria against Atractylodes Chinensis Root Rot and Their Effects.

Fusarium root rot (FRR) seriously affects the growth and productivity of A. chinensis. Therefore, protecting A. chinensis from FRR has become an important task, especially for increasing A. chinensis production. The purpose of this study was to screen FRR control strains from the A. chinensis rhizosphere soil. Eighty-four bacterial strains and seven fungal strains were isolated, and five strains were identified with high inhibitory effects against Fusarium oxysporum (FO): Trichoderma harzianum (MH), Bacillus amyloliquefaciens (CJ5, CJ7, and CJ8), and Bacillus subtilis (CJ9). All five strains had high antagonistic effects in vitro. Results showed that MH and CJ5, as biological control agents, had high control potential, with antagonistic rates of 86.01% and 82.78%, respectively. In the pot experiment, the growth levels of roots and stems of A. chinensis seedlings treated with MH+CJ were significantly higher than those of control plants. The total nitrogen, total phosphorus, total potassium, indoleacetic acid, and chlorophyll contents in A. chinensis leaves were also significantly increased. In the biocontrol test, the combined MH + CJ application significantly decreased the malondialdehyde content in A. chinensis roots and significantly increased the polyphenol oxidase, phenylalanine ammonolyase, and peroxidase ability, indicating a high biocontrol effect. In addition, the application of Bacillus spp. and T. harzianum increased the abundance and diversity of the soil fungal population, improved the soil microbial community structure, and significantly increased the abundance of beneficial strains, such as Holtermanniella and Metarhizium. The abundance of Fusarium, Volutella, and other pathogenic strains was significantly reduced, and the biocontrol potential of A. chinensis root rot was increased. Thus, Bacillus spp. and T. harzianum complex bacteria can be considered potential future biocontrol agents for FRR.

M2 Macrophage-Derived Extracellular Vesicles Containing MicroRNA-501-3p Promote Colon Cancer Progression Through the SETD7/DNMT1/SOCS3 Axis.

BACKGROUND: Macrophage-derived extracellular vesicles with microRNAs can cause and develop colon cancer. OBJECTIVE: To investigate M2 macrophage-derived extracellular vesicles and colon cancer. DESIGN: A prospective and experimental study of M2 macrophage-derived extracellular vesicles in colon cancer. SETTING: This study was completed at the Fourth Hospital of Hebei Medical University. PATIENTS: Patients with colon cancer who had undergone surgical resection. MAIN OUTCOME MEASURES: Suppressor of cytokine signaling 3, miR-501-3p, SET domain containing 7, and DNA methyltransferase 1 were measured in colon cancer samples. Multiple experiments determined suppressor of cytokine signaling 3, miR-501-3p, SET domain containing 7, and DNA methyltransferase 1 binding affinity. M2 macrophages were cultivated from M0 macrophages isolated from peripheral blood mononuclear cells of a healthy donor and polarized to produce extracellular vesicles. Gain- or loss-of-function tests using colon cancer cells and M2 macrophage-derived extracellular vesicles revealed cell biological processes. Finally, animal models were created to test how miR-501-3p from M2-extracellular vesicles affects tumor growth via the SET domain containing 7/DNA methyltransferase 1/suppressor of cytokine signaling 3. RESULTS: Colon cancer increased miR-501-3p and DNA methyltransferase 1 and downregulated suppressor of cytokine signaling 3 and SET domain containing 7. miR-151-3p inhibited SET domain containing 7, upregulating DNA methyltransferase 1. Increased promoter methylation by DNA methyltransferase 1 decreased suppressor of cytokine signaling 3 expression. M2-EVs with miR-501-3p regulated the SET domain containing 7/DNA methyltransferase 1/suppressor of cytokine signaling 3 axis to induce apoptosis and colon cancer cell growth, invasion, and migration. M2-EV-delivered miR-501-3p also regulated the SET domain containing 7/DNA methyltransferase 1/suppressor of cytokine signaling 3 axis to promote tumor growth in animals. LIMITATIONS: Further research is needed in clinical application of M2 macrophage-derived extracellular vesicles containing miR-501-3p as a biomarker of colon cancer. CONCLUSIONS: M2 macrophage-derived extracellular vesicles with miR-501-3p regulate the SET domain containing 7/DNA methyltransferase 1/suppressor of cytokine signaling 3 axis to promote colon cancer. LAS VESCULAS EXTRACELULARES DERIVADAS DE MACRFAGOS M QUE CONTIENEN MICROARNP PROMUEVEN LA PROGRESIN DEL CNCER DE COLON A TRAVS DEL EJE SETD/DNMT/SOCS: ANTECEDENTES:Las vesículas extracelulares derivadas de macrófagos con microARN pueden causar y desarrollar cáncer de colon.OBJETIVO:Investigamos las vesículas extracelulares derivadas de macrófagos M2 y el cáncer de colon.DISEÑO:Un estudio prospectivo y experimental de vesículas extracelulares derivadas de macrófagos M2 en el cáncer de colon.ESCENARIO:Este estudio se completó en el Cuarto Hospital de la Universidad Médica de Hebei.PACIENTES:Pacientes con cáncer de colon sometidos a resección quirúrgica.PRINCIPALES MEDIDAS DE RESULTADO:Se midieron el supresor de la señalización de citoquinas 3, miR-501-3p, SETD7 y la ADN metiltransferasa 1 en muestras de cáncer de colon. Múltiples experimentos determinaron la afinidad de unión del supresor de la señalización de citoquinas 3, de miR-501-3p, de SETD7 y de la ADN metiltransferasa 1. Los macrófagos M2 se cultivaron a partir de macrófagos M0 aislados de células mononucleares de sangre periférica de donantes sanos y se polarizaron para producir vesículas extracelulares. Las pruebas de ganancia o pérdida de función utilizando células de cáncer de colon y vesículas extracelulares derivadas de macrófagos M2 revelaron procesos biológicos celulares. Finalmente, se crearon modelos animales para probar cómo miR-501-3p de vesículas extracelulares M2 afecta el crecimiento tumoral a través del SETD7/ADN metiltransferasa 1/supresor de la señalización de citocinas 3.RESULTADOS:El cáncer de colon aumentó el miR-501-3p y la ADN metiltransferasa 1 y reguló negativamente el supresor de la señalización de citoquinas 3 y SETD7. miR-151-3p inhibió SETD7, regulando positivamente la ADN metiltransferasa 1. El aumento de la metilación del promotor por la ADN metiltransferasa 1 produjo disminución de la expresión del supresor de señalización de citocinas 3. Los M2-EV con miR-501-3p regularon el eje SETD7/ADN metiltransferasa 1/supresor de la señalización de citocinas 3 para inducir apoptosis y crecimiento, invasión y migración de células de cáncer de colon. El miR-501-3p administrado por M2-EV también reguló el eje SETD7/ADN metiltransferasa 1/supresor de la señalización de citocinas 3 para promover el crecimiento tumoral en animales.LIMITACIONES:Se necesita más investigación en la aplicación clínica de vesículas extracelulares derivadas de macrófagos M2 que contienen miR-501-3p como biomarcador de cáncer de colon.CONCLUSIONES:Las vesículas extracelulares derivadas de macrófagos M2 con miR-501-3p regulan el eje SETD7/ADN metiltransferasa 1/supresor de la señalización de citocinas 3 para promover el cáncer de colon. (Traducción-Dr. Felipe Bellolio ).

Efficacy of fractional CO2 laser therapy combined with hyaluronic acid dressing for treating facial atrophic acne scars: a systematic review and meta-analysis of randomized controlled trials.

The present work aimed to systematically identify the efficacy and safety of fractional carbon dioxide (CO2) laser plus hyaluronic acid (HA) dressing in dealing with facial atrophic acne scars. Randomized controlled trials (RCTs) concerning fractional CO2 laser in combination with HA dressing for treating atrophic acne scars were screened in 8 electronic databases (containing PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Internet, Wanfang, Sinomed as well as VIP). Besides, for the purpose of evaluating the risk of bias of the enrolled RCTs, the Cochrane Collaboration tool was adopted. Statistical analysis was completed using Revman5.3 software and Stata 14.0 software. Meanwhile, the quality of evidence was assessed by the GRADE system. Finally, 6 studies involving 623 patients were enrolled. According to the findings in this study, compared with fractional CO2 laser alone, fractional CO2 laser therapy combined with HA dressing reduced the scores of ECCA (échelle d'évaluation clinique des cicatrices d'acné) grading scale (MD=-3.37,95% CI [-5.03, -1.70], P<0.0001), shortened the time of crust formation (MD=-0.42,95% CI [-0.80, -0.04], P=0.03) and the time of crust removal(MD=-1.31,95% CI [-1.67, -0.95], P<0.00001), enhanced patient satisfaction (RR=1.85, 95% CI [1.44, 2.38], P<0.00001). All the reported adverse events including hyperpigmentation, erythema, edema, mild itching, and slight burning pain were controllable. In addition, fractional CO2 laser combined with HA dressing therapy had a lower incidence of hyperpigmentation than fractional CO2 laser alone (RR=0.37, 95% CI [0.23, 0.61], P<0.0001). The level of evidence for outcomes was classified to be low to moderate. According to our findings, fractional CO2 laser combined with HA dressing is efficacious and safe option for facial atrophic acne scars. Nevertheless, more high-quality trials are required for further verification in the future.

The role of vaccination route with an adenovirus-vectored vaccine in protection, viral control, and transmission in the SARS-CoV-2/K18-hACE2 mouse infection model.

Introduction: Vaccination is the most effective mechanism to prevent severe COVID-19. However, breakthrough infections and subsequent transmission of SARS-CoV-2 remain a significant problem. Intranasal vaccination has the potential to be more effective in preventing disease and limiting transmission between individuals as it induces potent responses at mucosal sites. Methods: Utilizing a replication-deficient adenovirus serotype 5-vectored vaccine expressing the SARS-CoV-2 RBD (AdCOVID) in homozygous and heterozygous transgenic K18-hACE2, we investigated the impact of the route of administration on vaccine immunogenicity, SARS-CoV-2 transmission, and survival. Results: Mice vaccinated with AdCOVID via the intramuscular or intranasal route and subsequently challenged with SARS-CoV-2 showed that animals vaccinated intranasally had improved cellular and mucosal antibody responses. Additionally, intranasally vaccinated animals had significantly better viremic control, and protection from lethal infection compared to intramuscularly vaccinated animals. Notably, in a novel transmission model, intranasal vaccination reduced viral transmission to naïve co-housed mice compared to intramuscular vaccination. Discussion: Our data provide convincing evidence for the use of intranasal vaccination in protecting against SARS-CoV-2 infection and transmission.

A Nano-Autophagy Inhibitor Triggering Reciprocal Feedback Control of Cholesterol Depletion for Solid Tumor Therapy.

Solid tumors are characterized by enhanced metabolism of lipid, particularly cholesterol, inspiring the exploration of metabolic therapy through cholesterol oxidase (COD)-mediated cholesterol deprivation. However, the therapeutic efficacy of COD is limited due to the hypoxic tumor microenvironment and the protective autophagy triggered by cholesterol deprivation. Herein, a combination therapy for metabolically treating solid tumors through COD in conjunction with molybdenum oxide nanodots (MONDs), which serve as both potent oxygen generators and autophagy inhibitors, is reported. MONDs convert H2 O2 (arising from COD-mediated cholesterol oxidation) into O2 , which is then recycled by COD to form reciprocal feedback for cholesterol depletion. Concurrently, MONDs can overcome autophagy-induced therapeutic resistance frequently occurring in conventional nutrient deprivation therapy by activating AKT/mTOR pathway phosphorylation. Combination therapy in the xenograft model results in an ≈5-fold increase in therapeutic efficiency as compared with COD treatment alone. This functionally cooperative metabolic coupling strategy holds great promise as a novel polytherapy approach that will benefit patients with solid tumors.