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Abstract Glioma is the most common and aggressive type of primary malignant brain tumor. The N6-methyladenosine (m6A) modification widely exists in eukaryotic cells and plays an important role in the occurrence and development of human tumors. However, the function and mechanism of heterogeneous nuclear ribonucleoprotein C (HNRNPC), an RNA-binding protein and m6A reader in gliomas remains to be comprehensively and extensively explored. Herein, we found that HNRNPC mRNA and protein overexpression were associated with a poor prognosis for patients with gliomas, based on the data from TCGA, the CGGA, and the TMAs. Biologically, HNRNPC knockdown markedly repressed malignant phenotypes of glioma in vitro and in vivo, whereas ectopic HNRNPC expression had the opposite effect. Integrative RNA sequencing and MeRIP sequencing analyses identified interleukin-1 receptor-associated kinase 1 (IRAK1) as a downstream target of HNRNPC. The glioma public datasets and tissue microarrays (TMAs) data indicated that IRAK1 overexpression was associated with poor prognosis, and IRAK1 knockdown significantly repressed malignant biological behavior in vitro. Mechanistically, HNRNPC maintains the mRNA stability of IRAK1 in an m6A-dependent manner, resulting in activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which was necessary for the malignant behavior of glioma. Our findings demonstrate the HNRNPC–IRAK1–MAPK axis as a crucial carcinogenic factor for glioma and the novel underlying mechanism of IRAK1 upregulation, which provides a rationale for therapeutically targeting epitranscriptomic modulators in glioma.

The separation of light hydrocarbon compounds is an important process in the chemical industry. Currently, its separation methods mainly include distillation, membrane separation, and physical adsorption. However, these traditional methods or materials have some drawbacks and disadvantages, such as expensive equipment costs and high energy consumption, poor selectivity, low separation ratios, and separation efficiencies. Therefore, it is important to develop novel separation materials for light hydrocarbon separation. As a new type of organic–inorganic hybrid crystalline material, metal–organic frameworks (MOFs) are promising materials for light hydrocarbon separation due to their designability of structure and easy modulation of function. This review provides an overview of recent advances in the design, synthesis, and application of MOFs for light hydrocarbon separation in recent years, with a focus on the separation of alkane, alkene, and alkyne. We discuss strategies for improving the adsorption selectivity and capacity of MOFs, including pore size limitation, physical adsorption, and chemisorption. In addition, we discuss the advantages/disadvantages, challenges, and prospects of MOFs in the separation of light hydrocarbon.

Background: The latissimus dorsi (LD) flap procedure remains a popular and useful breast reconstruction tool in China and Western countries, and donor site seroma formation is the main complication. This study was conducted in Chinese patients to determine whether stable cases of seromas would resolve without treatment. Methods: A retrospective review of 45 consecutive cases of immediate breast reconstruction with LD flap from April 2012 to February 2017 was conducted. The scope of the seroma was demarcated with a marker pen, and cases that remained stable over time (i.e. the size of the seroma did not increase) were observed without treatment. The measured outcomes included the incidence of seromas, the volume and duration of postoperative wound drainage, and other demographic characteristics. Results: Twenty-four patients (53.3%) developed a seroma at the donor site. Of these, 21 patients (87.5%) did not require treatment, and the seroma resolved over time. The mean duration of a sustained seroma was 6.8 ± 1.4 weeks (range: 4–9 weeks). Conclusions: This study observed the scope and progression of the seromas and found that seromas at the LD donor sites resolved over time without treatment.

Introduction: Plant growth-promoting rhizobacteria (PGPR) and elevated CO2 (eCO2) have demonstrated their individual potential to enhance plant yield and quality through close interaction with rhizosphere microorganisms and plant growth. However, the efficacy of PGPR under eCO2 on rhizosphere microbiome and, ultimately, plant yield and active ingredient accumulation are not yet fully understood. Methods: This study investigated how the medicinal plant Pseudostellaria heterophylla (P. heterophylla) and its rhizosphere microbes respond to PGPR (Bacillus subtilis and Pseudomonas fluorescens) at eCO2 (1,000 ppm). Results and Discussion: It was found that the yield and active ingredient polysaccharides accumulation in the tuber of P. heterophylla were significantly increased by 38 and 253%, respectively. This promotion has been associated with increased root development and changes in the indigenous microbial community. Metagenomics analysis revealed a significant reduction in pathogenic Fusarium abundance in the rhizosphere. Potential biocontrol bacteria Actinobacteria and Proteobacteria were enriched, especially the genera Bradyrhizobium and Rhodanobacter. The reshaping of the rhizosphere microbiome was accompanied by the upregulation of biological pathways related to metabolite biosynthesis in the rhizosphere. These modifications were related to the promotion of the growth and productivity of P. heterophylla. Our findings highlighted the significant role played by PGPR in medicinal plant yield and active ingredient accumulation when exposed to eCO2. [ABSTRACT FROM AUTHOR]

Background The effect of a healthy lifestyle on dementia associated with multimorbidity is not well understood. Our objective is to examine whether the adoption of a healthy lifestyle could potentially reduce the elevated risk of dementia in individuals with and without multimorbidity. Methods We utilized data from the UK Biobank cohort. A comprehensive healthy lifestyle score, ranging from 0 to 6, was generated. Cox proportional hazards models were used to examine the associations between multimorbidity, the healthy lifestyle score, and the incidence risk of dementia. Results Over a median follow-up period of 12.5 years, 5 852 all-cause dementia were recorded. Multimorbidity including cardiovascular, metabolic, neuropsychiatric, and inflammation-related diseases was associated with a higher risk of subsequent dementia. Each additional chronic disease was associated with a hazard ratio (HR) of 1.38 (95% CI: 1.33, 1.44). Compared to individuals without multimorbidity and a healthy lifestyle score of 5–6, patients with multimorbidity and a lifestyle score of 0–1 had a significantly higher risk of dementia (HR: 3.13; 95% CI: 2.64, 3.72), but the risk was markedly attenuated among those with multimorbidity and a lifestyle score of 5–6. Among patients with 3 or more diseases, the HR for dementia was 0.53 (95%CI: 0.42, 0.68) when comparing a lifestyle score of 5–6 to 0–1. And we observed more pronounced association between them among people younger than 60 years old. Conclusions Adherence to a combination of healthy lifestyle factors, especially at a young age, was associated with a significantly lower risk of dementia among participants with multimorbidity. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate the clinical efficacy and safety of Buzhong Tiaogan granule (BTG) in treatment of colorectal cancer patients with liver metastasis and provide high-level evidence for clinical practice.Methods and analysisThis is a prospective, randomized, controlled, multi-center controlled trial. A total of 210 patients diagnosed with spleen deficiency and liver depression, as well as colorectal cancer liver metastasis (CRLM) of the stasis and toxin interception type, will be enrolled in the study. The participants will be randomly allocated into two groups: a treatment group that will receive BTG plus conventional first-line anti-tumor therapy and a control group that will receive conventional first-line anti-tumor therapy alone. The primary outcomes are progression-free survival (PFS) and quality of life scores. The secondary outcomes are as follows: (a) overall survival (OS); (b) objective response rate (ORR); (c) liver-specific progression-free survival; (d) disease control rate (DCR); (e) traditional Chinese medicine (TCM) syndrome score; (f) Piper Fatigue Scale, and (g) Karnofsky Performance Status (KPS) score. Safety evaluations will be conducted throughout the study period.DiscussionThe results of this trial will provide scientific and objective data necessary for the evaluation of the efficacy and safety of BTG for colorectal cancer patients with liver metastasis.Clinical trial registrationThe trial was registered at ClinicalTrials.gov (ChiCTR2400084861) on May 27, 2024.

Abstract The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses. In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies. More importantly, mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus (VACV) lethal challenge mouse model, and a unique mRNA antibody cocktail, Mix2a, exhibited superior in vivo protection by targeting both intracellular mature virus (IMV)-form and extracellular enveloped virus (EEV)-form viruses. In summary, our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform, highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as other emerging viruses.

Pulmonary anthrax is the most fatal clinical form of anthrax and currently available injectable vaccines do not provide adequate protection against it. Hence, next-generation vaccines that effectively induce immunity against pulmonary anthrax are urgently needed. In the present study, we prepared an attenuated and low protease activity Bacillus anthracis strain A16R-5.1 by deleting five of its extracellular protease activity-associated genes and its lef gene through the CRISPR-Cas9 genome editing system. This mutant strain was then used to formulate a lethal toxin (LeTx)-free culture supernatant extract (CSE) anthrax vaccine, of which half was protective antigen (PA). We generated liquid, powder, and powder reconstituted formulations that could be delivered by aerosolized intratracheal inoculation. All of them induced strong humoral, cellular, and mucosal immune responses. The vaccines also produced LeTx neutralizing antibodies and conferred full protection against the lethal aerosol challenges of B. anthracis Pasteur II spores in mice. Compared to the recombinant PA vaccine, the CSE anthrax vaccine with equal PA content provided superior immunoprotection against pulmonary anthrax. The preceding results suggest that the CSE anthrax vaccine developed herein is suitable and scalable for use in inhalational immunization against pulmonary anthrax.

Zika virus (ZIKV) is primarily transmitted through mosquito bites and sexual contact, and vertical transmission of ZIKV has also been observed in humans. In addition, ZIKV infection via unknown transmission routes has been frequently reported in clinical settings. However, whether ZIKV can be transmitted via aerosol routes remains unknown. In this study, we demonstrated that aerosolized ZIKV is fully infectious in vitro and in vivo. Remarkably, intratracheal (i.t.) inoculation with aerosolized ZIKV led to rapid viremia and viral secretion in saliva, as well as robust humoral and innate immune responses in guinea pigs. Transcriptome analysis further revealed that the expression of genes related to viral processes, biological regulation and the immune response was significantly changed. Together, our results confirm that aerosolized ZIKV can result in systemic infection and induce both innate and adaptive immune responses in guinea pigs, highlighting the possibility of ZIKV transmission via aerosols.

Targeted therapy has been standardized in front-line therapies for metastatic colorectal cancer (mCRC), while explicit recommendations for third- or later-line are still lacking. This study evaluated the efficacy and safety of combining targeted therapy with chemotherapy in the third- or later-line treatment for mCRC via meta-analysis, providing evidence-based guidance for clinical or research practice. Comprehensive retrieval of related studies was conducted according to the PRISMA guideline. Studies were stratified with patient characteristics and pharmacological classification of the drugs. For the data available for quantitative analysis, pooled overall response rate, disease control rate, hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and adverse events rate with respective 95% confidence intervals (CIs) were calculated. A total of 22 studies (1,866 patients) were included in this meta-analysis. Data from 17 studies (1,769 patients) involving targets of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) were extracted for meta-analyses. The overall response rates for monotherapy and combined therapy were 4% (95% CI: 3%, 5%) and 20% (95% CI: 11%, 29%). The pooled HRs (combined therapy vs. mono) for OS and PFS were 0.72 (95% CI: 0.53, 0.99) and 0.34 (95% CI: 0.26, 0.45). Another five studies were included in narrative depiction, involving targets of BRAF, HER-2, ROS1, and NTRK. The findings of this meta-analysis indicate that VEGF and EGFR inhibitors manifest promising clinical response rates and prolonged survival in the treatment of mCRC with acceptable adverse events.

Abstract. Gastric cancer (GC) is a common malignancy and is the third leading cause of cancer-related death. At present, there is no simple and effective screening method for early-stage GC, and the treatment results and prognosis are poor. With the continuous improvement of molecular biology techniques, research on circular RNA (circRNA) has gradually expanded over time. Much data supports the role of circRNA in tumorigenesis. Moreover, due to its structural specificity and biological stability, circRNA is anticipated to be a potential biomarker for tumor diagnosis. Studies have confirmed that circRNA can participate in the proliferation, invasion, metastasis, and apoptosis of GC. These findings will lead to novel directions for the diagnosis and treatment of GC. This article reviews the structure and function of circRNA, summarizes the current studies on circRNA, and discusses the potential diagnostic value of circRNA in GC.

Abstract. Background. In the era of precision medicine, chemotherapy is still considered the cornerstone of treatment for lung cancer patients without gene mutations. How to reduce the toxicity and increase the efficiency of chemotherapy is worth exploring. This study aimed to investigate the curative effects and safety of hyperthermia combined with chemotherapy (HCT) for advanced patients with non-small cell lung cancer (NSCLC), especially those with malignant pleural effusion. Methods. We retrospectively evaluated medical records of 93 patients with advanced NSCLC (stage IIIB-IV) from March 2011 to January 2014. The patients were divided into HCT and chemotherapy (CT) groups. The HCT group was treated with gemcitabine and cisplatin (GP) regimen combined with regional radiofrequency deep hyperthermia, while the CT group was treated with GP regimen only. Those with malignant pleural effusion extra underwent thoracentesis and intrapleural injection chemotherapy combined with hyperthermic or not. Clinical treatment results and adverse reactions were compared and analyzed after treatment. SPSS 19.0 software (SPSS Inc., USA) was used for statistical data processing. P values less than 0.05 were accepted to be statistically significant. Results. Among the 93 patients, HCT group included 48 patients (16 patients with malignant pleural effusion), CT group included 45 patients (10 patients with malignant pleural effusion). There was no significant difference between the two groups in patient characteristics. The overall response rate (ORR) of pleural effusions was much better in HCT group than that in CT group (81.2% vs. 40.0%, P = 0.046). The patients in HCT group had lower incidence rate of weakness (12.5% vs. 46.7%, χ2 = 13.16, P

Anti-angiogenesis therapy, by blocking formation of new blood vessels in tumors, is the standard-of-care therapy for various cancer types. The classic concept of anti-angiogenesis is expected to turn a tumor into a âdormantâ disease. However, the combination of anti-angiogenesis agents with conventional therapeutics has generally produced only modest survival benefits for cancer patients in clinical trials. Therefore, the concept and applications of anti-angiogenesis have evolved dramatically along with lessons learned from recent clinical experience. In this article, we will discuss the revised concept of anti-angiogenesis therapy and the applications of anti-angiogenesis drugs, and focus particularly on how to utilize current anti-angiogenesis agents and develop new approaches to provide more benefits to patients with cancer. Keywords: Anti-angiogenesis, Angiogenesis, Vascular endothelial growth factor, Cancer

IntroductionPlant growth-promoting rhizobacteria (PGPR) and elevated CO2 (eCO2) have demonstrated their individual potential to enhance plant yield and quality through close interaction with rhizosphere microorganisms and plant growth. However, the efficacy of PGPR under eCO2 on rhizosphere microbiome and, ultimately, plant yield and active ingredient accumulation are not yet fully understood.MethodsThis study investigated how the medicinal plant Pseudostellaria heterophylla (P. heterophylla) and its rhizosphere microbes respond to PGPR (Bacillus subtilis and Pseudomonas fluorescens) at eCO2 (1,000 ppm).Results and DiscussionIt was found that the yield and active ingredient polysaccharides accumulation in the tuber of P. heterophylla were significantly increased by 38 and 253%, respectively. This promotion has been associated with increased root development and changes in the indigenous microbial community. Metagenomics analysis revealed a significant reduction in pathogenic Fusarium abundance in the rhizosphere. Potential biocontrol bacteria Actinobacteria and Proteobacteria were enriched, especially the genera Bradyrhizobium and Rhodanobacter. The reshaping of the rhizosphere microbiome was accompanied by the upregulation of biological pathways related to metabolite biosynthesis in the rhizosphere. These modifications were related to the promotion of the growth and productivity of P. heterophylla. Our findings highlighted the significant role played by PGPR in medicinal plant yield and active ingredient accumulation when exposed to eCO2.

The application of soil beneficial bacteria (SBB) in agriculture is steadily increasing as it provides a promising way to replace chemical fertilisers and other supplements. Although the role of SBB as a biofertiliser is well understood, little is known about the response of soil physiochemical properties via the change in soil enzymatic activities with SBB growth. In this study, sterilised bulk soil was inoculated with Bacillus subtilis (BS) and Pseudomonas fluorescens (PF), which exhibit excellent characteristics in vitro for potentially improving soil quality. It is found that the contents of bioavailable nitrogen and ammonium in soil inoculated with SBB increased significantly, up to 34% and 57% relative to a control. This resulted from the enhancement of soil urease activity with BS and PF treatments by approximately 90% and 70%, respectively. The increased soil urease activity can be explained by the increased microorganism activity evident from the larger population size of BS (0.78–0.97 CFU mL−1/CFU mL−1) than PF (0.55–0.79 CFU mL−1/CFU mL−1) (p < 0.05). Results of principal component analysis also reinforce the interaction apparent in the significant relationship between soil urease activity and microbial biomass carbon (p < 0.05). Therefore, it can be concluded that the enhancement of soil enzymatic activities induced bulk soil fertility upregulation because of bacterial growth. These results demonstrate the application of SBB to be a promising strategy for bulk soil amendment, particularly nutrient restoration.