Sinomonas terricola sp. nov., a plant-beneficial bacterium isolated from litchi rhizosphere soil in Guangdong, China.

A novel plant-beneficial bacterium strain, designated as JGH33T, which inhibited Peronophythora litchii sporangia germination, was isolated on Reasoner's 2A medium from a litchi rhizosphere soil sample collected in Gaozhou City, Guangdong Province, PR China. Cells of strain JGH33T were Gram-stain-positive, aerobic, non-motile, bent rods. The strain grew optimally at 30-37 °C and pH 6.0-8.0. Sequence similarity analysis based on 16S rRNA genes indicated that strain JGH33T exhibited highest sequence similarity to Sinomonas albida LC13T (99.2 %). The genomic DNA G+C content of the isolate was 69.1 mol%. The genome of JGH33T was 4.7 Mbp in size with the average nucleotide identity value of 83.45 % to the most related reference strains, which is lower than the species delineation threshold of 95 %. The digital DNA-DNA hybridization of the isolate resulted in a relatedness value of 24.9 % with its closest neighbour. The predominant respiratory quinone of JGH33T was MK-9(H2). The major fatty acids were C15 : 0 anteiso (43.4 %), C16 : 0 iso (19.1 %) and C17 : 0 anteiso (19.3 %), and the featured component was C18 : 3 ω6c (1.01 %). The polar lipid composition of strain JGH33T included diphosphatidylglycerol, phosphatidylglycerol, dimannosylglyceride, phosphatidylinositol and glycolipids. On the basis of polyphasic taxonomy analyses data, strain JGH33T represents a novel species of the genus Sinomonas, for which the name Sinomonas terricola sp. nov. is proposed, with JGH33T (=JCM 35868T=GDMCC 1.3730T) as the type strain.

The Macrophage migration inhibitory factor is a vital player in Pan-Cancer by functioning as a M0 Macrophage biomarker.

BACKGROUND: The role of the macrophage migration inhibitory factor (MIF) has recently attracted considerable attention in cancer research; nonetheless, the insights provided by current investigations remain constrained. Our main objective was to investigate its role and the latent mechanisms within the pan-cancer realm. METHODS: We used comprehensive pan-cancer bulk sequencing data and online network tools to investigate the association between MIF expression and patient prognosis, genomic instability, cancer cell stemness, DNA damage repair, and immune infiltration. Furthermore, we validated the relationship between MIF expression and M0 macrophages using single-cell datasets, the SpatialDB database, and fluorescence staining. Additionally, we assessed the therapeutic response using the ROC plotter tool. RESULTS: We observed the upregulation of MIF expression across numerous cancer types. Notably, elevated MIF levels were associated with a decline in genomic stability. We found a significant correlation between increased MIF expression and increased expression of mismatch repair genes, stemness features, and homologous recombination genes across diverse malignancies. Subsequently, through an analysis using ESTIMATE and cytokine results, we revealed the involvement of MIF in immune suppression. Then, we validated MIF as a hallmark of the M0 macrophages involved in tumor immunity. Our study suggests an association with other immune-inhibitory cellular populations and restraint of CD8 + T cells. In addition, we conducted a comparative analysis of MIF expression before and after treatment in three distinct sets of therapy responders and non-responders. Intriguingly, we identified notable disparities in MIF expression patterns in bladder urothelial carcinoma and ovarian cancer following particular therapeutic interventions. CONCLUSION: Comprehensive pan-cancer analysis revealed notable enrichment of MIF within M0 macrophages, exerting a profound influence on tumor-associated immunosuppression and the intricate machinery of DNA repair.

Characterization of NMCR-3, NMCR-4 and NMCR-5, three novel non-mobile colistin resistance determinants: Implications for MCR-3, MCR-7, and MCR-5 progenitors, respectively.

In this study, the progenitors of MCR-3, MCR-7 and MCR-5, namely NMCR-3, NMCR-4 and NMCR-5, were firstly discovered and indicating Aeromonas was a natural reservoir for MCR-3 and MCR-7. Furthermore, different evolutionary models for MCR-3, MCR-7 and MCR-5 were proposed.

Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method.

Cancer immunotherapy with autologous chimeric antigen receptor (CAR) T cells faces challenges in manufacturing and patient selection that could be avoided by using 'off-the-shelf' products, such as allogeneic CAR natural killer T (AlloCAR-NKT) cells. Previously, we reported a system for differentiating human hematopoietic stem and progenitor cells into AlloCAR-NKT cells, but the use of three-dimensional culture and xenogeneic feeders precluded its clinical application. Here we describe a clinically guided method to differentiate and expand IL-15-enhanced AlloCAR-NKT cells with high yield and purity. We generated AlloCAR-NKT cells targeting seven cancers and, in a multiple myeloma model, demonstrated their antitumor efficacy, expansion and persistence. The cells also selectively depleted immunosuppressive cells in the tumor microenviroment and antagonized tumor immune evasion via triple targeting of CAR, TCR and NK receptors. They exhibited a stable hypoimmunogenic phenotype associated with epigenetic and signaling regulation and did not induce detectable graft versus host disease or cytokine release syndrome. These properties of AlloCAR-NKT cells support their potential for clinical translation.

Discovery of LHQ490 as a highly selective fibroblast growth factor receptor 2 (FGFR2) inhibitor.

Fibroblast growth factor receptor 2 (FGFR2) represents an appealing therapeutic target for multiple cancers, yet no selective FGFR2 inhibitors have been approved for clinical use to date. Here, we report the discovery of a series of new selective, irreversible FGFR2 inhibitors. The representative compound LHQ490 potently inhibited FGFR2 kinase activity with an IC50 of 5.2 nM, and was >61-, >34-, and >293-fold selective against FGFR1, FGFR3, and FGFR4, respectively. LHQ490 also exhibited high selectivity in a panel of 416 kinases. Cell-based studies revealed that LHQ490 efficiently suppressed the proliferation of BaF3-FGFR2 cells with an IC50 value of 1.4 nM, and displayed >70- and >714-fold selectivity against BaF3-FGFR1 and the parental BaF3 cells, respectively. More importantly, LHQ490 potently suppressed the FGFR2 signaling pathways, selectively inhibited FGFR2-driven cancer cell proliferation, and induced apoptosis of FGFR2-driven cancer cells. Taken together, this study provides a potent and highly selective FGFR2 inhibitor for further development of FGFR2-targeted therapeutic agents.

Human molybdenum exposure risk in industrial regions of China: New critical effect indicators and reference dose.

Evidence increasingly suggests molybdenum exposure at environmental levels is still associated with adverse human health, emphasizing the necessity to establish a more protective reference dose (RfD). Herein, we conducted a study measuring 15 urinary metals and 30 clinical health indicators in 2267 participants residing near chemical enterprises across 11 Chinese provinces to investigate their relationships. The kidney and cystatin-C emerged as the most sensitive organ and critical effect indicator of molybdenum exposure, respectively. Odds of cystatin-C-defined chronic kidney disease (CKD) in the highest quantile of molybdenum exposure significantly increased by 133.5% (odds ratio [OR]: 2.34, 95% CI: 1.78, 3.11) and 75.8% (OR: 1.76, 95% CI: 1.24, 2.49) before and after adjusting for urinary 14 metals, respectively. Intriguingly, cystatin-C significantly mediated 15.9-89.5% of molybdenum's impacts on liver and lung function, suggesting nephrotoxicity from molybdenum exposure may trigger hepatotoxicity and pulmonary toxicity. We derived a new RfD for molybdenum exposure (0.87 µg/kg-day) based on cystatin-C-defined estimated glomerular filtration rate by employing Bayesian Benchmark Dose modeling analysis. This RfD is significantly lower than current exposure guidance values (5-30 µg/kg-day). Remarkably, >90% of participants exceeded the new RfD, underscoring the significant health impacts of environmental molybdenum exposure on populations in industrial regions of China.

Antitumor Activity and Mechanistic Insights of a Mitochondria-Targeting Cu(I) Complex.

Using copper-ionophores to translocate extracellular copper into mitochondria is a clinically validated anticancer strategy that has been identified as a new type of regulated cell death termed "cuproptosis." This study reports a mitochondria-targeting Cu(I) complex, Cu(I)Br(PPh3)3 (CBP), consisting of a cuprous ion coordinated by three triphenylphosphine moieties and a Br atom. CBP exhibited antitumor and antimetastatic efficacy in vitro and in vivo by specifically targeting mitochondria instigating mitochondrial dysfunction. The cytotoxicity of CBP could only be reversed by a copper chelator rather than inhibitors of the known cell death, indicating copper-dependent cytotoxicity. Furthermore, CBP induced the oligomerization of lipoylated proteins and the loss of Fe-S cluster proteins, consistent with characteristic features of cuproptosis. Additionally, CBP induced remarkable intracellular generation of reactive oxygen species (ROS) through a Fenton-like reaction, indicating a complex antitumor mechanism. This is a proof-of-concept study exploiting the antitumor activity and mechanism of the Cu(I)-based mitochondria-targeting therapy.

The Scheduling Mode of Anesthesia Nurses Affects Postanesthesia Care Unit Efficiency: A Single-Center Retrospective Study From China.

PURPOSE: Anesthesia nurses play an important postsurgical role during the anesthesia recovery period, which is characterized by a high incidence of complications related to anesthesia and surgery. Strengthening staff allocation and skill management in the postanesthesia care unit (PACU) is therefore particularly important in managing length of stay. We aimed to investigate the effect of two schedule modes for anesthesia nurses on PACU efficiency. DESIGN: A retrospective observational cohort study. METHODS: We conducted a retrospective study in a large tertiary academic medical center. In 2018, the PACU operated with traditional scheduling and the nurse-to-patient ratio was 1.2:1. The PACU implemented intensive scheduling and this ratio was adjusted to 1:1 in 2019 by adjusting the anesthesia nurse allocation scheme. We compared the number of admitted patients, length of PACU stay, the incidence of anesthesia-related complications, and nurse satisfaction with the two modes. FINDINGS: The total number of admitted patients was 10,531 in 2018 and 10,914 in 2019. PACU admitted 401 more patients in 2019 than in 2018, even with two fewer nurses per day. Nevertheless, the median length of PACU stay in 2019 was statistically significantly shorter than in 2018 (29 [22-40] vs 28 [21-39], P < .001], while the incidence of anesthesia-related complications including postoperative pain, nausea and vomiting, hypertension, and shivering were comparable in the 2 years (P > .091). The intensive scheduling implemented in 2019 received more satisfaction from nurses than the traditional scheduling applied in 2018 (P < .01). CONCLUSIONS: The scheduling of anesthesia nurses affects PACU efficiency. The intensive scheduling mode implemented in 2019 resulted in a comparable number of admitted patients, a better quality of care, and higher nurse satisfaction than those under the traditional scheduling mode.

A study of the migration behavior of formaldehyde in different concentrations of ethanol in paper food materials.

To ensure the safety of food contact materials, a liquid chromatography method was established to determine the migration of formaldehyde in paper packaging with various food simulants (10%, 25%, 50%, 75%, and 95% ethanol by volume) and to investigate the migration behavior of formaldehyde after various durations and with various materials. The results showed that the method has good linearity with a correlation coefficient of R2 > 0.9990, a detection limit of 0.0011 ~ 0.0027 mg L-1, and a spiked recovery of 89.7 ~ 103.2% in the range of formaldehyde determination; the migration of formaldehyde in all six paper contact materials showed a trend of gradual increase with time until equilibrium was reached. At the same time and temperature, the migration of formaldehyde in paper packaging was the highest in low-concentration ethanol. With the same food simulants and materials, the maximum migration of formaldehyde in printed materials was greater than that in nonprinted materials; with different materials and the same food simulant, the thickness value was higher, with the use of water-based ink as a printing material, and the maximum migration value of formaldehyde by offset printing technology was low.

Protocol to prepare MUC1 glycopeptide vaccines and evaluate immunization effects in mice.

The tumor-associated mucin MUC1 is overexpressed in almost all types of epithelial tumor tissues, making it an attractive target antigen for cancer immunotherapy. Here we present a protocol to prepare MUC1 glycopeptide vaccines and to evaluate immunization effects in mice. We describe steps for synthesizing glycopeptide antigen and conjugating it with carrier protein to make vaccine candidates. We then detail procedures for mice immunization, antibody response evaluation, and cellular immune response. For complete details on the use and execution of this protocol, please refer to Cai et al.1,2.

Cancer Immunotherapy and Medical Imaging Research Trends from 2003 to 2023: A Bibliometric Analysis.

Purpose: With the rapid development of immunotherapy, cancer treatment has entered a new phase. Medical imaging, as a primary diagnostic method, is closely related to cancer immunotherapy. However, until now, there has been no systematic bibliometric analysis of the state of this field. Therefore, the main purpose of this article is to clarify the past research trajectory, summarize current research hotspots, reveal dynamic scientific developments, and explore future research directions. Patients and Methods: A comprehensive search was conducted on the Web of Science Core Collection (WoSCC) database to identify publications related to immunotherapy specifically for the medical imaging of carcinoma. The search spanned the period from the year 2003 to 2023. Several analytical tools were employed. These included CiteSpace (6.2.4), and the Microsoft Office Excel (2016). Results: By searching the database, a total of 704 English articles published between 2003 and 2023 were obtained. We have observed a rapid increase in the number of publications since 2018. The two most active countries are the United States (n=265) and China (n=170). Pittock, Sean J and Abu-sbeih, Hamzah are very concerned about the relationship between cancer immunotherapy and medical images and have published more academic papers (n = 5; n = 4). Among the top 10 co-cited authors, Topalian Sl (n=43) cited ranked first, followed by Graus F (n=40) cited. According to clustering, timeline, and burst word analysis, the results show that the current research focus is on "MRI", "deep learning", "tumor microenvironment" and so on. Conclusion: Medical imaging and cancer immunotherapy are hot topics. The United States is the country with the most publications and the greatest influence in this field, followed by China. "MRI", "PET/PET-CT", "deep learning", "immune-related adverse events" and "tumor microenvironment" are currently hot research topics and potential targets.

ß-Lapachone, an NQO1 bioactivatable drug, prevents lung tumorigenesis in mice.

Lung cancer is one of the most lethal cancers with high incidence worldwide. The prevention of lung cancer is of great significance to reducing the social harm caused by this disease. An in-depth understanding of the molecular changes underlying precancerous lesions is essential for the targeted chemoprevention against lung cancer. Here, we discovered an increased NQO1 level over time within pulmonary premalignant lesions in both the KrasG12D-driven and nicotine-derived nitrosamine ketone (NNK)-induced mouse models of lung cancer, as well as in KrasG12D-driven and NNK-induced malignant transformed human bronchial epithelial cells (BEAS-2B and 16HBE). This suggests a potential correlation between the NQO1 expression and lung carcinogenesis. Based on this finding, we utilized ß-Lapachone (ß-Lap), an NQO1 bioactivatable drug, to suppress lung tumorigenesis. In this study, the efficacy and safety of low-dose ß-Lap were demonstrated in preventing lung tumorigenesis in vivo. In conclusion, our study suggests that long-term consumption of low-dose ß-Lap could potentially be an effective therapeutic strategy for the prevention of lung premalignant lesions. However, further studies and clinical trials are necessary to validate our findings, determine the safety of long-term ß-Lap usage in humans, and promote the use of ß-Lap in high-risk populations.

Primary Epithelioid Angiosarcoma of the Jejunal Mesentery Causing Abdominal Bleeding: Case Report and Literature Review.

Gastrointestinal angiosarcoma is an extremely rare malignant tumor of the digestive tract, characterized by a very poor prognosis, with few patients surviving more than 1 year after diagnosis. This case report describes a 71-year-old female patient with a 3-year history of intermittent abdominal pain and significant exacerbation of abdominal pain and bloating 2 weeks prior to treatment. After surgical treatment, the pathological and immunohistochemical diagnosis was primary epithelioid angiosarcoma of the jejunal mesentery. The patient refused postoperative adjuvant chemotherapy and died 4 months after diagnosis due to widespread systemic metastasis. In addition, this article reviews 38 previously reported cases of primary gastrointestinal angiosarcoma, aiming to further understand angiosarcoma and thus guide clinical practitioners in providing more comprehensive treatment approaches.

The oncogenic role and regulatory mechanism of ACAA2 in human ovarian cancer.

Acetyl-CoAacyltransferase2 (ACAA2) is a key enzyme in the fatty acid oxidation pathway that catalyzes the final step of mitochondrial ß oxidation, which plays an important role in fatty acid metabolism. The expression of ACAA2 is closely related to the occurrence and malignant progression of tumors. However, the function of ACAA2 in ovarian cancer is unclear. The expression level and prognostic value of ACAA2 were analyzed by databases. Gain and loss of function were carried out to explore the function of ACAA2 in ovarian cancer. RNA-seq and bioinformatics methods were applied to illustrate the regulatory mechanism of ACAA2. ACAA2 overexpression promoted the growth, proliferation, migration, and invasion of ovarian cancer, and ACAA2 knockdown inhibited the malignant progression of ovarian cancer as well as the ability of subcutaneous tumor formation in nude mice. At the same time, we found that OGT can induce glycosylation modification of ACAA2 and regulate the karyoplasmic distribution of ACAA2. OGT plays a vital role in ovarian cancer as a function of oncogenes. In addition, through RNA-seq sequencing, we found that ACAA2 regulates the expression of DIXDC1. ACAA2 regulated the malignant progression of ovarian cancer through the WNT/ß-Catenin signaling pathway probably. ACAA2 is an oncogene in ovarian cancer and has the potential to be a target for ovarian cancer therapy.

The prognostic nutritional index as a predictor of efficacy and early recurrence for adjuvant transarterial chemoembolization in hepatocellular carcinoma.

BACKGROUND AND AIMS: Postoperative adjuvant transcatheter arterial chemoembolization (TACE) can prevent recurrence of hepatocellular carcinoma (HCC) in certain patients. This study aimed to identify the potential beneficiaries of adjuvant TACE. METHODS: 477 patients who underwent curative resection for HCC were enrolled in this retrospectively cohort study. The trajectory of the prognostic nutritional index (PNI) during the perioperative period was fitted using a latent-class growth mixed model. The association between adjuvant TACE and recurrence-free survival in each PNI group was assessed using the Kaplan-Meier curve. Furthermore, Cox regression analysis was conducted to identify the risk factors for early recurrence after adjuvant TACE and develop a nomogram model. RESULTS: Patients in the PNI group III had a high risk of recurrence and could benefit from adjuvant TACE (P = 0.009). The prognostic prediction model for adjuvant TACE (PAT) incorporated eight variables (PNI, tumor size, tumor number, microvascular invasion, sex, aspartate aminotransferase, gamma-glutamyl transferase, and degree of differentiation). Patients with PAT score >330 and 235-330 had significantly higher recurrence rates than those with PAT score <235 (P < 0.001). CONCLUSION: PNI may help guide the selection of adjuvant TACE beneficiaries. PAT demonstrated a high accuracy in predicting the prognosis of patients who underwent postoperative TACE.

Engineering allorejection-resistant CAR-NKT cells from hematopoietic stem cells for off-the-shelf cancer immunotherapy.

The clinical potential of current FDA-approved chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy is encumbered by its autologous nature, which presents notable challenges related to manufacturing complexities, heightened costs, and limitations in patient selection. Therefore, there is a growing demand for off-the-shelf universal cell therapies. In this study, we have generated universal CAR-engineered NKT (UCAR-NKT) cells by integrating iNKT TCR engineering and HLA gene editing on hematopoietic stem cells (HSCs), along with an ex vivo, feeder-free HSC differentiation culture. The UCAR-NKT cells are produced with high yield, purity, and robustness, and they display a stable HLA-ablated phenotype that enables resistance to host cell-mediated allorejection. These UCAR-NKT cells exhibit potent antitumor efficacy to blood cancers and solid tumors, both in vitro and in vivo, employing a multifaceted array of tumor-targeting mechanisms. These cells are further capable of altering the tumor microenvironment by selectively depleting immunosuppressive tumor-associated macrophages and myeloid-derived suppressor cells. In addition, UCAR-NKT cells demonstrate a favorable safety profile with low risks of graft-versus-host disease and cytokine release syndrome. Collectively, these preclinical studies underscore the feasibility and significant therapeutic potential of UCAR-NKT cell products and lay a foundation for their translational and clinical development.

STAT5 phosphorylation plus minimal residual disease defines a novel risk classification in adult B-cell acute lymphoblastic leukaemia.

The dysregulation of the Janus family tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) is closely related to acute lymphoblastic leukaemia (ALL), whereas the clinical value of phosphorylated STAT5 (pSTAT5) remains elusive. Herein we performed a prospective study on clinical significance of flow cytometry-based pSTAT5 in adult B-ALL patients. A total of 184 patients were enrolled in the Precision-Classification-Directed-Target-Total-Therapy (PDT)-ALL-2016 cohort between January 2018 and December 2021, and STAT5 phosphorylation was detected by flow cytometry at diagnosis. Based on flow-pSTAT5, the population was classified into pSTAT5low (113/184, 61.1%) and pSTAT5high (71/184, 38.9%). Overall survival (OS) and event-free survival (EFS) were inferior in pSTAT5high patients than in those with pSTAT5low (OS, 44.8% vs. 65.2%, p = 0.004; EFS, 23.5% vs. 52.1%, p < 0.001), which was further confirmed in an external validation cohort. Furthermore, pSTAT5 plus flow-based minimal residual disease (MRD) postinduction defines a novel risk classification as being high risk (HR, pSTAT5high + MRD+), standard risk (SR, pSTAT5low + MRD-) and others as moderate-risk group. Three identified patient subgroups are distinguishable with disparate survival curves (3-year OS rates, 36.5%, 56.7% and 76.3%, p < 0.001), which was confirmed on multivariate analysis (hazard ratio 3.53, p = 0.003). Collectively, our study proposed a novel, simple and flow-based risk classification by integrating pSTAT5 and MRD in favour of risk-guided treatment for B-ALL.

Adaptation process of decellularized vascular grafts as hemodialysis access in vivo.

Arteriovenous grafts (AVGs) have emerged as the preferred option for constructing hemodialysis access in numerous patients. Clinical trials have demonstrated that decellularized vascular graft exhibits superior patency and excellent biocompatibility compared to polymer materials; however, it still faces challenges such as intimal hyperplasia and luminal dilation. The absence of suitable animal models hinders our ability to describe and explain the pathological phenomena above and in vivo adaptation process of decellularized vascular graft at the molecular level. In this study, we first collected clinical samples from patients who underwent the construction of dialysis access using allogeneic decellularized vascular graft, and evaluated their histological features and immune cell infiltration status 5 years post-transplantation. Prior to the surgery, we assessed the patency and intimal hyperplasia of the decellularized vascular graft using non-invasive ultrasound. Subsequently, in order to investigate the in vivo adaptation of decellularized vascular grafts in an animal model, we attempted to construct an AVG model using decellularized vascular grafts in a small animal model. We employed a physical-chemical-biological approach to decellularize the rat carotid artery, and histological evaluation demonstrated the successful removal of cellular and antigenic components while preserving extracellular matrix constituents such as elastic fibers and collagen fibers. Based on these results, we designed and constructed the first allogeneic decellularized rat carotid artery AVG model, which exhibited excellent patency and closely resembled clinical characteristics. Using this animal model, we provided a preliminary description of the histological features and partial immune cell infiltration in decellularized vascular grafts at various time points, including Day 7, Day 21, Day 42, and up to one-year post-implantation. These findings establish a foundation for further investigation into the in vivo adaptation process of decellularized vascular grafts in small animal model.

Molecular Modeling of Shockwave-Mediated Blood-Brain Barrier Opening for Targeted Drug Delivery.

Bubble-enhanced shock waves induce the transient opening of the blood-brain barrier (BBB) providing unique advantages for targeted drug delivery of brain tumor therapy, but little is known about the molecular details of this process. Based on our BBB model including 28 000 lipids and 280 tight junction proteins and coarse-grained dynamics simulations, we provided the molecular-level delivery mechanism of three typical drugs for the first time, including the lipophilic paclitaxel, hydrophilic gemcitabine, and siRNA encapsulated in liposome, across the BBB. The results show that the BBB is more difficult to be perforated by shock-induced jets than the human brain plasma membrane (PM), requiring higher shock wave speeds. For the pores formed, the BBB exhibits a greater ability to self-heal than PM. Hydrophobic paclitaxel can cross the BBB and be successfully absorbed, but the amount is only one-third of that of PM; however, the absorption of hydrophilic gemcitabine was almost negligible. Liposome-loaded siRNAs only stayed in the first layer of the BBB. The mechanism analysis shows that increasing the bubble size can promote drug absorption while reducing the risk of higher shock wave overpressure. An exponential function was proposed to describe the relation between bubble and overpressure, which can be extended to the experimental microbubble scale. The calculated overpressure is consistent with the experimental result. These molecular-scale details on shock-assisted BBB opening for targeted drug delivery would guide and assist experimental attempts to promote the application of this strategy in the clinical treatment of brain tumors.

The TRIF-RIPK1-Caspase-8 signalling in the regulation of TLR4-driven gene expression.

The inflammatory response is tightly regulated to eliminate invading pathogens and avoid excessive production of inflammatory mediators and tissue damage. Caspase-8 is a cysteine protease that is involved in programmed cell death. Here we show the TRIF-RIPK1-Caspase-8 is required for LPS-induced CYLD degradation in macrophages. TRIF functions in the upstream of RIPK1. The homotypic interaction motif of TRIF and the death domain of RIPK1 are essential for Caspase-8 activation. Caspase-8 cleaves CYLD and the D235A mutant is resistant to the protease activity of Caspase-8. TRIF and RIPK1 serve as substrates of Capase-8 in vitro. cFLIP interacts with Caspase-8 to modulate its protease activity on CYLD and cell death. Deficiency in TRIF, Caspase-8 or CYLD can lead to a decrease or increase in the expression of genes encoding inflammatory cytokines. Together, the TRIF-Caspase-8 and CYLD play opposite roles in the regulation of TLR4 signalling.