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ABSTRACT Burns are one of the most common injuries in both civilian and combat settings and are difficult to treat. This is particularly true when the wounds are infected with antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). A new generation of safe, broadly effective, and easily applied anti-infection agents is needed to successfully prevent and treat infections. Nanoemulsions (NEs) are nanometer-sized particles with a positively charged surfactant at their oil-water interface. In the current study, we further investigated antimicrobial NEs as a treatment to address burn wounds infected by MRSA. Specifically, using a porcine skin model, we infected partial thickness thermal burn wounds with MRSA and then treated it with the nanoemulsion formulation (NB-201) or placebo controls. Bacterial viability after treatment was determined, and inflammation indexes in wounds were scored by histopathology. Topical treatment of infected wounds with NB-201 resulted in reduced colony-forming units (CFUs) compared to placebo treatment. In addition, NB-201 was effective in significantly alleviating inflammation in the treated wounds and promoting wound healing. These results indicate that NB-201 is a promising new agent to treat skin burn wounds infected with MRSA.IMPORTANCEThe findings of this study are focused on therapeutic applications of nanotechnology. In the current study, we demonstrated that a nanoemulsion formulation could effectively kill methicillin-resistant Staphylococcus aureus (MRSA) infection in porcine skin burn wounds. Infection of MRSA in burn wound is a common threat to public health and is usually difficult to treat due to limited therapies available. NB-201 was effective in significantly alleviating inflammation in the treated wounds and promoting wound healing. Therefore, the finding of this study has a great potential to make this formulation a novel antimicrobial agent against MRSA.

Much effort has been devoted to improving treatment efficiency for osteosarcoma (OS). However, most current approaches result in poor therapeutic responses, thus indicating the need for the development of other therapeutic options. This study developed a multifunctional nanoparticle, PDA-MOF-E-M, an aggregation of OS targeting, programmed death targeting, and near-infrared (NIR)-aided targeting. At the same time, a multifunctional nanoparticle that utilises Fe-MOFs to create a cellular iron-rich environment and erastin as a ferroptosis inducer while ensuring targeted delivery to OS cells through cell membrane encapsulation is presented. The combination of PDA-MOF-E-M and PTT increased intracellular ROS and LPO levels and induced ferroptosis-related protein expression. A PDA-based PTT combined with erastin showed significant synergistic therapeutic improvement in the anti-tumour efficiency of the nanoparticle in vitro and vivo. The multifunctional nanoparticle efficiently prevents the osteoclasia progression of OS xenograft bone tumors in vivo. Finally, this study provides guidance and a point of reference for clinical approaches to treating OS.

The integrated stress response, especially stress granules (SGs), contributes to host immunity. Typical G3BP1+ stress granules (tSGs) are usually formed after virus infection to restrain viral replication and stimulate innate immunity. Recently, several SG-like foci or atypical SGs (aSGs) with proviral function have been found during viral infection. We have shown that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein induces atypical N+/G3BP1+ foci (N+foci), leading to the inhibition of host immunity and facilitation of viral infection. However, the precise mechanism has not been well clarified yet. In this study, we showed that the SARS-CoV-2 N (SARS2-N) protein inhibits dsRNA-induced growth arrest and DNA damage-inducible 34 (GADD34) expression. Mechanistically, the SARS2-N protein promotes the interaction between GADD34 mRNA and G3BP1, sequestering GADD34 mRNA into the N+foci. Importantly, we found that GADD34 participates in IRF3 nuclear translocation through its KVRF motif and promotes the transcription of downstream interferon genes. The suppression of GADD34 expression by the SARS2-N protein impairs the nuclear localization of IRF3 and compromises the host’s innate immune response, which facilitates viral replication. Taking these findings together, our study revealed a novel mechanism by which the SARS2-N protein antagonized the GADD34-mediated innate immune pathway via induction of N+foci. We think this is a critical strategy for viral pathogenesis and has potential therapeutic implications.

Background It has been a consensus that cardiac rehabilitation is an effective comprehensive intervention for patients with coronary heart disease (CHD), but the quality of relevant guidelines is still unclear, and recommendations from the guidelines need to be integrated. Objective To systematically review the guidelines on cardiac rehabilitation in patients with CHD, providing evidence to inform clinical practice. Methods In June 2022, guidelines on cardiac rehabilitation in patients with CHD were searched in electronic databases of the Cochrane Library, Web of Science, PubMed, CNKI, CQVIP and Wanfang Data, relevant guideline repositories and association websites from inception to 30 June 2022. Literature screening and data extraction were performed by two researchers separately according to the inclusion and exclusion criteria. The quality of included guidelines was assessed using the Appraisal of Guidelines for Research & EvaluationⅡ (AGREEⅡ), and recommendations from which were summarized. Results Ten guidelines (eight of them are foreign guidelines) with publication time ranging from 2011 to 2020 were eventually included. The average score of every AGREEⅡ domain was 71% for scope and purpose, 65% for stakeholder involvement, 58% for rigor of development, 80% for clarity of presentation, 64% for applicability, and 45% for editorial independence. Four guidelines were rated as grade A and the remaining six as grade B. Six aspects are involved in recommendations, including basic requirements of cardiac rehabilitation, heath education, risk factors control, psychological support, exercise training, and improvement of cardiac rehabilitation participation. Conclusion The quality of included guidelines is at a moderate to high level. More efforts are needed to improve the domains in stakeholder involvement, rigor of development, applicability, and editorial independence. Recommendations of the 10 guidelines tend to be consistent, but there are still insufficient recommendations on improving cardiac rehabilitation participation. There is a gap in the quality between domestic and foreign guidelines, so it is necessary to develop a high-quality guideline on cardiac rehabilitation for patients with CHD in China.

Gastric cancer (GC) is one of the most common tumors; one of the reasons for its poor prognosis is that GC cells can resist normal cell death process and therefore develop distant metastasis. Cuproptosis is a novel type of cell death and a limited number of studies have been conducted on the relationship between cuproptosis-related genes (CRGs) in GC. The purpose of the present study was to establish a prognostic model of CRGs and provide directions for the diagnosis and treatment of GC. Transcriptome and clinical data of patients with GC were collected from The Cancer Genome Atlas and Gene Expression Omnibus datasets. Single sample gene set enrichment analysis (GSEA) and the randomized forest method were used to establish the prognostic model. Kaplan-Meier survival curve, receiver operating characteristics diagram and a nomogram were used to evaluate the reliability of the model. GSEA and gene set variation analysis (GSVA) were used to examine enrichment pathways between high and low risk groups. Finally, immunohistochemical analysis was used to examine ephrin 4 (EFNA4) expression in GC samples and determine the prognosis of patients with GC based on the expression pattern of EFNA4. A group of 7 predictive models (RTKN2, INO80B, EFNA4, ELF2, MUSTN, KRTAP4, and ARHGEF40) was established which were correlated with CRGs. This model can be used as an independent prognostic factor to predict the prognosis of patients with GC. GSEA and GSVA results indicated that high risk patients with GC were mainly associated with the enrichment of ANGIOGENESIS and TGF_BETA_SIGNALING pathways. Finally, EFNA4 expression in GC was significantly higher than that in normal tissues, and patients with GC and high EFNA4 expression exhibited improved prognosis. In conclusion, the prognosis model based on CRGs could be used as the basis for predicting the potential prognosis of patients with GC and provide new insights for the treatment of GC. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the role of ROS/MAPK signaling pathways and the effects of baicalin in LPS-induced inflammatory responses in mice and porcine intestinal epithelial cells (IPEC-J2). Methods: In vivo, 18 male C57BL/6J mice were randomly divided into three groups (n = 6): control, LPS (3.5 mg/kg LPS administered intraperitoneally [ip] on day 7), and baicalin (200 mg/kg orally for 7 days, with LPS ip on day 7). On day 8, mice were sacrificed, and jejunal tissues were collected for H&E staining. ROS levels in serum and cytokine protein expressions (TNF-α and IL-6) in the jejunum were measured via ELISA, while intestinal MAPK proteins were analyzed using Western blotting. In vitro, the study involved two experimental setups: NAC (a ROS scavenger) and baicalin. For the NAC experiment, IPEC-J2 cells were divided into three groups: control, LPS, and NAC. In the LPS group, cells were treated with LPS (40 μg/mL) for 1 h. In the NAC group, cells were pretreated with NAC prior to LPS exposure. For the baicalin experiment, IPEC-J2 cells were divided into five groups: control, LPS, and baicalin at low (10 μM), medium (20 μM), and high (40 μM) doses. Cells were pretreated with baicalin for 24 h before LPS exposure. ROS/LDH levels and cytokine expressions in the supernatant were determined via ELISA, and MAPK protein expressions were assessed using Western blotting. Results: In vivo, LPS-induced oxidative stress and inflammatory responses in the intestine, reduced the villus height-to-crypt ratio, and significantly increased protein expressions of p-ERK, p-P38, JNK, and p-JNK (p < 0.05). Baicalin treatment significantly inhibited serum ROS levels (p < 0.01), reduced jejunal cytokine expressions (TNF-α and IL-6, p < 0.05), improved intestinal structural damage, and decreased p-ERK, p-P38, and p-JNK protein expressions (p < 0.05). In vitro, NAC significantly reduced ROS levels (p < 0.01), cytokine expressions (TNF-α and IL-6), and MAPK activation (ERK, JNK, P38, and their phosphorylated forms, p < 0.05). Baicalin also significantly decreased ROS (p < 0.05), TNF-α (p < 0.05), IL-6 (p < 0.05), and MAPK protein expressions (ERK, p-ERK, and p-P38, p < 0.05). Molecular docking demonstrated that baicalin effectively bound to ERK and P38 proteins. Conclusions: Baicalin mitigated LPS-induced inflammatory responses via the ROS/p-ERK/p-P38 signaling pathway in vivo and in vitro. [ABSTRACT FROM AUTHOR]

In order to reduce the exhaust noise, which is the main source of gasoline engine noise, this paper uses on orthogonal test to optimize the parameters of the main structure of split-stream rushing muffler (the perforation rate of the perforated pipe, perforation aperture of the perforated pipe, perforation rate of the perforated plate). It also comprehensively evaluates its acoustic and aerodynamic performances to determine the optimal structural model. The acoustic performance and aerodynamic performance of the split-stream rushing muffler and the original muffler are compared and analyzed in the simulation test. The results show that the average Transmission Loss of the split-stream rushing muffler is greater than that of the original muffler, and its Pressure Loss is also lower than that of the original muffler. Through the insertion loss experiment, it was found that the average insertion loss of the main muffling frequency band is 19.14 dB, which is higher than that of the original muffler, and the peak frequency of the insertion loss of the split-stream rushing muffler corresponds well with the peak frequency of the engine exhaust noise. The Pressure Loss of the split-stream rushing muffler was tested on the experiment bench, and the relative error between the experiment data and the simulation data is within 8%. In summary, the split-stream rushing muffler can effectively reduce the exhaust noise problem of gasoline engines. [ABSTRACT FROM AUTHOR]

Diesel engines employed in non-road machinery are significant contributors to nanoparticulate matters. This paper presents a novel device based on the principle of split-stream rushing to mitigate particulate matter emissions from these engines. By organizing and intensifying the airflow movement of the jet in the rushing region, the probability of collisions between nanoparticles is enhanced. This accelerates the growth and coagulation of nanoparticles, reducing the number density of fine particulate matter. This, in turn, facilitates the capture or sedimentation of particulate matter in the diesel engine exhaust aftertreatment system. The coagulation kernel function tailored for diesel engine exhaust nanoparticles is developed. Then, the particle balance equation is solved to investigate the evolution and coagulation characteristics. Afterwards, three-dimensional numerical simulations are performed to study the flow field characteristics of the split-stream rushing device and the particle evolution within it. The results show that the device achieves a maximum coagulation efficiency of 59.73%, increasing the average particle diameter from 96 nm to 121 nm. The particle number density uniformity index exceeded 0.93 in most flow regions, highlighting the effectiveness of the device in ensuring consistent particle distribution. [ABSTRACT FROM AUTHOR]