Development of a clinical nomogram for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer.

BACKGROUND: The efficacy of neoadjuvant chemotherapy (NAC) in advanced gastric cancer (GC) is still a controversial issue. AIM: To find factors associated with chemosensitivity to NAC treatment and to provide the optimal therapeutic strategies for GC patients receiving NAC. METHODS: The clinical information was collected from 230 GC patients who received NAC treatment at the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2016 to December 2020. Least absolute shrinkage and selection operator logistic regression analysis was used to find the possible predictors. A nomogram model was employed to predict the response to NAC. RESULTS: In total 230 patients were finally included in this study, including 154 males (67.0%) and 76 females (33.0%). The mean age was (59.37 ± 10.60) years, ranging from 24 years to 80 years. According to the tumor regression grade standard, there were 95 cases in the obvious response group (grade 0 or grade 1) and 135 cases in the poor response group (grade 2 or grade 3). The obvious response rate was 41.3%. Least absolute shrinkage and selection operator analysis showed that four risk factors significantly related to the efficacy of NAC were tumor location (P < 0.001), histological differentiation (P = 0.001), clinical T stage (P = 0.008), and carbohydrate antigen 724 (P = 0.008). The C-index for the prediction nomogram was 0.806. The calibration curve revealed that the predicted value exhibited good agreement with the actual value. Decision curve analysis showed that the nomogram had a good value in clinical application. CONCLUSION: A nomogram combining tumor location, histological differentiation, clinical T stage, and carbohydrate antigen 724 showed satisfactory predictive power to the response of NAC and can be used by gastrointestinal surgeons to determine the optimal treatment strategies for advanced GC patients.

Characteristics and molecular mechanism of drug-tolerant cells in cancer: a review.

Drug resistance in tumours has seriously hindered the therapeutic effect. Tumour drug resistance is divided into primary resistance and acquired resistance, and the recent study has found that a significant proportion of cancer cells can acquire stable drug resistance from scratch. This group of cells first enters the drug tolerance state (DT state) under drug pressure, and gradually acquires stable drug resistance through adaptive mutations in this state. Although the specific mechanisms underlying the formation of drug tolerant cells (DTCs) remain unclear, various proteins and signalling pathways have been identified as being involved in the formation of DTCs. In the current review, we summarize the characteristics, molecular mechanisms and therapeutic strategies of DTCs in detail.

A review of deubiquitinases and thier roles in tumorigenesis and development.

Ubiquitin is a small protein that can be added onto target protein for inducing target degradation, thereby modulating the activity and stability of protein. Relatively, deubiquitinases (DUBs), a class catalase that can remove ubiquitin from substrate protein, provide a positive regulation of the protein amount at transcription level, post-translational modification, protein interaction, etc. The reversible and dynamic ubiquitination-deubiquitination process plays an essential role in maintaining protein homeostasis, which is critical to almost all the biological processes. Therefore, the metabolic dysregulation of deubiquitinases often lead to serious consequences, including the growth and metastasis of tumors. Accordingly, deubiquitinases can be served as key drug targets for the treatment of tumors. The small molecule inhibitors targeting deubiquitinases has become one of the hot spots of anti-tumor drug research areas. This review concentrated on the function and mechanism of deubiquitinase system in the proliferation, apoptosis, metastasis and autophagy of tumor cells. The research status of small molecule inhibitors of specific deubiquitinases in tumor treatment is introduced, aiming to provide reference for the development of clinical targeted drugs.

Tripartite motif-containing protein 31 confers protection against nonalcoholic steatohepatitis by deactivating mitogen-activated protein kinase kinase kinase 7.

BACKGROUND AIMS: As a global health threat, NASH has been confirmed to be a chronic progressive liver disease that is strongly associated with obesity. However, no approved drugs or efficient therapeutic strategies are valid, mainly because its complicated pathological processes is underestimated. APPROACH RESULTS: We identified the RING-type E3 ubiquitin transferase-tripartite motif-containing protein 31 (TRIM31), a member of the E3 ubiquitin ligases family, as an efficient endogenous inhibitor of transforming growth factor-beta-activated kinase 1 (mitogen-activated protein kinase kinase kinase 7; MAP3K7), and we further confirmed that TRIM31 is an MAP3K7-interacting protein and promotes MAP3K7 degradation by enhancing ubiquitination of K48 linkage in hepatocytes. Hepatocyte-specific Trim31 deletion blocks hepatic metabolism homeostasis, concomitant with glucose metabolic syndrome, lipid accumulation, up-regulated inflammation, and dramatically facilitates NASH progression. Inversely, transgenic overexpression, lentivirus, or adeno-associated virus-mediated Trim31 gene therapy restrain NASH in three dietary mice models. Mechanistically, in response to metabolic insults, TRIM31 interacts with MAP3K7 and conjugates K48-linked ubiquitination chains to promote MAP3K7 degradation, thus blocking MAP3K7 abundance and its downstream signaling cascade activation in hepatocytes. CONCLUSIONS: TRIM31 may serve as a promising therapeutic target for NASH treatment and associated metabolic disorders.

The role of O-GlcNAcylation in innate immunity and inflammation.

O-linked ß-N-acetylglucosaminylation (O-GlcNAcylation) is a highly dynamic and widespread post-translational modification (PTM) that regulates the activity, subcellular localization, and stability of target proteins. O-GlcNAcylation is a reversible PTM controlled by two cycling enzymes: O-linked N-acetylglucosamine transferase and O-GlcNAcase. Emerging evidence indicates that O-GlcNAcylation plays critical roles in innate immunity, inflammatory signaling, and cancer development. O-GlcNAcylation usually occurs on serine/threonine residues, where it interacts with other PTMs, such as phosphorylation. Thus, it likely has a broad regulatory scope. This review discusses the recent research advances regarding the regulatory roles of O-GlcNAcylation in innate immunity and inflammation. A more comprehensive understanding of O-GlcNAcylation could help to optimize therapeutic strategies regarding inflammatory diseases and cancer.

Water reduces iron toxicity.

An 86-year-old man presented to the emergency room with vomiting and melena. The patient was hemodynamically stable and remained alert and orientated. According to his family, ingestion of a pack of disposable hand warmers, which he mistook for black sesame powder, occurred 17 h prior to admission. Before ingestion, he mixed the powder with warm water. Physical examination revealed no thermal injury of the oral mucosa with no abdominal pain or tenderness. An abdominal plain film showed multiple scattered radiopaque material with zonal distribution over the right abdomen. An intravenous 500-mg deferoxamine challenge test showed no vin rosé urine discoloration. Serial serum iron levels remained within the normal range. The patient remained clinically stable with no medical complications. He was discharged 3 days after admission. The hand warmers consisted of iron powder (50% w/w), sodium chloride, activated charcoal, and nontoxic vermiculite: a potential risk for intestinal thermal injury. In this case, the water added beforehand rapidly terminated the iron oxidation reaction. This explained the lack of thermal injury. Ferric oxide is poorly absorbed by the digestive tract and explained the absence of iron intoxication. Therefore, clinicians should clarify the method of ingestion. If a hand warmer has been premixed with water, less mucosa injury can be expected with a lower risk of iron intoxication. This report also provided evidence that abdominal plain films can be used to confirm the ingestion of iron and monitor its elimination.

Association Between Neddylation and Immune Response.

Neddylation is a ubiquitin-like post-translational protein modification. It occurs via the activation of the neural precursor cell expressed, developmentally downregulated protein 8 (NEDD8) by three enzymes: activating enzyme, conjugating enzyme, and ligase. NEDD8 was first isolated from the mouse brain in 1992 and was initially considered important for the development and differentiation of the central nervous system. Previously, the downregulation of neddylation was associated with some human diseases, such as neurodegenerative disorders and cancers. In recent years, neddylation has also been proven to be pivotal in various processes of the human immune system, including the regulation of inflammation, bacterial infection, viral infection, and T cell function. Additionally, NEDD8 was found to act on proteins that can affect viral transcription, leading to impaired infectivity. Here, we focused on the influence of neddylation on the innate and adaptive immune responses.

Choices of Specialties and Training Sites among Taiwanese Physicians Graduating from Polish Medical Schools.

Taiwanese students who graduated from Polish medical schools (P-IMGs) accounted for the second-largest group of international medical graduates in Taiwan. In 2009, domestic medical students in Taiwan staged mass demonstrations against P-IMG's exemption from the qualifying test before the licensing exam. Although medical circles in Taiwan might still hold prejudices against P-IMGs, little is known about their career development. This study will analyze P-IMGs' choices of specialties and training sites from 2000 to 2020 using data from the membership section of the Taiwan Medical Journal, the monthly official publication of the Taiwan Medical Association. Of 372 P-IMGs, 34.2% chose internal medicine and 17.1% surgery. Although academic medical centers offered 76% of all available trainee positions in a year, only 49.3% of P-IMGs received training there. By contrast, 20.9% of P-IMGs were trained at nonmetropolitan hospitals that altogether accounted for only 5.8% of trainee positions. In conclusion, P-IMGs had their residency training at less favorable specialties and sites. Their long-term career development deserves further study.

Function of Protein S-Palmitoylation in Immunity and Immune-Related Diseases.

Protein S-palmitoylation is a covalent and reversible lipid modification that specifically targets cysteine residues within many eukaryotic proteins. In mammalian cells, the ubiquitous palmitoyltransferases (PATs) and serine hydrolases, including acyl protein thioesterases (APTs), catalyze the addition and removal of palmitate, respectively. The attachment of palmitoyl groups alters the membrane affinity of the substrate protein changing its subcellular localization, stability, and protein-protein interactions. Forty years of research has led to the understanding of the role of protein palmitoylation in significantly regulating protein function in a variety of biological processes. Recent global profiling of immune cells has identified a large body of S-palmitoylated immunity-associated proteins. Localization of many immune molecules to the cellular membrane is required for the proper activation of innate and adaptive immune signaling. Emerging evidence has unveiled the crucial roles that palmitoylation plays to immune function, especially in partitioning immune signaling proteins to the membrane as well as to lipid rafts. More importantly, aberrant PAT activity and fluctuations in palmitoylation levels are strongly correlated with human immunologic diseases, such as sensory incompetence or over-response to pathogens. Therefore, targeting palmitoylation is a novel therapeutic approach for treating human immunologic diseases. In this review, we discuss the role that palmitoylation plays in both immunity and immunologic diseases as well as the significant potential of targeting palmitoylation in disease treatment.

The element of family medicine in the mega journal of the family medicine specialty: A bibliometric analysis of the journal, Chinese General Practice.

BACKGROUND: With the evolving specialization of modern medicine, family medicine (FM), also known as general practice, is relatively late in being recognized as a formal specialty in most countries of the world. Because many non-FM specialists were recruited into the new specialty in the early stages of FM specialization, the contents of FM specialty journals might, to an extent, reflect the development of the FM specialization. METHODS: In this study, the voluminous journal, Chinese General Practice, which is regarded as the most representative specialty journal, was chosen and analyzed to illustrate the current situation of FM in China. A total of 878 articles, relating to the journal, Chinese General Practice in 2018, were retrieved from the publisher's web site and the original articles were categorized into FM- and non-FM- related articles by 3 board-certified FM doctors. Furthermore, the first authors, as well as the institutions and regions where the first authors worked, and their related specialties, were also analyzed. RESULTS: Of the 634 original articles, 252 (39.7%) articles were FM related. Only 41 FM-related articles were written by authors working at FM departments: 3 at community health service centers, 29 at hospitals, and 9 at universities. Of the 382 non-FM related articles, 159 articles dealt with the topic of internal medicine, followed by traditional Chinese medicine (36), obstetrics and gynecology (28), neurology (27), pediatrics (27), and surgery (21). CONCLUSION: In conclusion, FM publications in China in the study year, as exemplified by Chinese General Practice, were mostly contributed by non-FM authors dealing with non-FM topics. A transition to more FM-oriented development might be anticipated in the near future.

Alternating stealth polymer coatings between administrations minimizes toxic and antibody immune responses towards nanomedicine treatment regimens.

In efforts to achieve minimal systemic toxicity and high tumor delivery efficiencies in cancer therapy, various nanomedicine formulations having stealth polymer coatings have been developed for minimizing immune cell uptake and off-target macrophage phagocyte system (MPS) organ accumulation. Despite an initial reduction in immune cell uptake, stealth nanoparticles still initiate an antibody immune response. This response acts on subsequent administrations in treatment regimens resulting in accelerated blood clearance of particles into MPS organs, particularly the liver, where they are retained for prolonged periods. Consequently, doses after the first administration in treatment regimens have diminished tumor accumulation and increased MPS toxicity. Here, we present a strategy reducing antibody responses to each dose in a treatment regimen by alternating between polyethylene-glycol and polymethyloxazoline polymers as the nanoparticle coating between administrations. In a weekly dosing regimen, we find that the first dose of particles having either coating display similar favorable pharmacokinetics and biodistributions, thus allowing the polymers to be used interchangeably. However, when maintaining the same coating in subsequent administrations, we find that particles are in circulation at the height of the antibody immune response resulting in 50-60% decreases of circulation half-lives and tumor accumulation along with 50% increases in liver accumulation. By alternating the polymers used in the nanoparticle coating between administrations, we find each dose maintains favorable in vivo behaviors at the height of the antibody immune response to the previous administration. Furthermore, our strategy increases the clearance of particles uptaken by macrophages and hepatocytes, resulting in marked decreases in hepatotoxicity.

The Combination of CA125 and NSE Is Useful for Predicting Liver Metastasis of Lung Cancer.

PURPOSE: Liver metastasis is the final stage of cancer progression and is associated with poor prognosis. Although numerous indicators have been identified as having prognostic value for lung cancer and liver metastasis, liver metastases are still not diagnosed by imaging in many patients. To provide a more accurate method for clinical prediction of liver metastasis, we analyzed multiple factors to identify potential predictive factors for liver metastasis of lung cancer. METHODS: Patients first diagnosed with lung cancer between 2002 and 2016 (n = 1746) were divided into two groups, with and without liver metastasis. Serum concentrations of calcium, carcinoembryonic antigen (CEA), cancer antigen-125 (CA125), cancer antigen-153 (CA153), carbohydrate antigen-199 (CA199), cytokeratin fraction 21-1 (CYFRA21-1), total prostate-specific antigen (TPSA), and neuron-specific enolase (NSE) were analyzed in both patient groups. RESULTS: There was no significant difference in age or sex between the two groups. CA125 and NSE were significantly associated with liver metastasis. Compared with CA125, NSE was more specific, while it was less sensitive (P < 0.001). Further analysis of NSE concentrations was conducted in patients with non-small-cell lung cancer and indicated that NSE concentration differed significantly between those with and without liver metastasis (P = 0.023). We conducted analysis with NSE and CA125 combined, resulting in acceptable sensitivity (51.2%), specificity (72.6%), and area under the curve (0.64) values; sensitivity and area under the curve values were higher than those for individual factors, while specificity was higher than that for CA125. CONCLUSIONS: The combination of CA125 and NSE can assist prediction of liver metastasis of lung cancer, providing improved diagnostic accuracy.

CYFRA21-1/TG ratio as an accurate risk factor to predict eye metastasis in nasopharyngeal carcinoma: A STROBE-compliant article.

Nasopharyngeal carcinoma (NPC) has a distinctive geographical distribution in China, especially southern China. There are several risk factors for NPC, such as Epstein-Barr virus, genetics, and environmental exposures. Although the incidence of eye metastasis (EM) is lower than metastasis in other body parts, it often indicates poor prognosis.We assessed several serum biomarkers for their ability to predict EM in NPC. Patients with NPC were selected (n = 963), and were separated into two groups, EM and no eye metastasis. Ten factors were analyzed in both groups including triglyceride (TG), high-density lipoprotein, low-density lipoprotein, alkaline phosphatase, alpha fetoprotein, carbohydrate antigen-199, cancer antigen-153, apolipoproteins AI, apolipoprotein B, and cytokeratin fragment 19 (CYFRA21-1). Independent t tests, binary logistic regression, and receiver operating characteristic curves were used to assess the data.The EM group had significantly higher CYFRA21-1 and lower TG compared with the no eye metastasis group. Areas under the curve for CYFRA21-1, TG and CYFRA21-1/TG were 0.966, 0.771, and 0.976, respectively. The corresponding cut-off values were 12.12 ng/ml, 0.41 mmol/L, and 13.5. The sensitivity and specificity of CYFRA21-1/TG were 100% and 92.2%, respectively.The increased ratio of CYFRA21-1 to TG can be an accurate method to detect EM in patients with NPC.

The Crosstalk Between Hippo-YAP Pathway and Innate Immunity.

Recognition of pathogen-associated molecular patterns (PAMPs) triggers expression of antiviral interferons and proinflammatory cytokines, which functions as the frontier of host defense against microbial pathogen invasion. Hippo-YAP pathway regulates cell proliferation, survival, differentiation and is involved in diverse life processes, including tissue homeostasis and tumor suppression. Emerging discoveries elucidated that the components of Hippo-YAP pathway, such as MST1/2, NDR1/2, and YAP/TAZ played crucial regulatory roles in innate immunity. Meanwhile the innate immune signaling also exhibited regulatory effect on Hippo-YAP pathway. As for the importance of these two pathways, it would be interesting to figure out the deeper biological implications of their interplays. This review focuses on the regulation between Hippo-YAP pathway and innate immune signaling. We also propose the possible contribution of these interplays to tumor development.

Comparison of two methods of locating proximal femoral nail anti-rotation in the treatment of femoral intertrochanteric fractures.

BACKGROUND: To compare the efficacy of three-point locating versus routine locating techniques for implanting helical blades for proximal femoral nail anti-rotation-II in the treatment of trochanteric fractures. METHODS: From January 2010 to June 2013, 90 patients with intertrochanteric fractures were surgically treated, including 48 males and 42 females with an average age of 70.5 ± 7.2 years. According to the AO classification, there were 45 cases of A2.1, 35 cases of A2.2, and 10 cases of A2.3. Based on locating techniques, the 90 patients were divided into two groups: the three-point group and the routine group, with 45 patients in each group. All operations were performed by the same group of surgeons using proximal femoral nail anti-rotation (PFNA); the helical blade was inserted into the femoral neck with the three-point locating technique or by the usual method according to treatment group. Several figures including total operation time, elapsed time for implanting the helical blade, intraoperative blood loss, X-ray exposure time, and tip-apex distance (TAD) were measured and compared. RESULTS: The three-point group was significantly superior as compared to the routine group in terms of total operation time [(59.34 ± 9.42) min vs (67.61 ± 12.63) min, P < 0.01], elapsed time for implanting the helical blade [(4.58 ± 1.25) min vs (7.82 ± 2.19) min, P < 0.01], intraoperative blood loss [(92.78 ± 34.09) ml vs (154.01 ± 39.10) ml, P < 0.01], X-ray exposure time [(8.84 ± 1.45) vs (14.62 ± 2.91), P < 0.01], and tip-apex distance [(16.78 ± 1.55) mm vs (21.91 ± 3.01) mm, P < 0.01]. Among the 90 patients, 80 were followed up for an average time of 12 months (10-15 months), including 42 patients who were part of three-point group and 38 patients who were part of the routine group. No spiral blade cut was found on the femoral head in any patient in the three-point group, whereas it occurred in 2 patients in the routine group 1 month after surgery. However, there was no significant difference in the Harris score between the two groups 6 months after the operation. CONCLUSION: The three-point locating method is faster and more accurate than the routine locating method.

Lots of little ones: Analysis of charitable donations to a hospice and palliative care unit in Taiwan.

BACKGROUND: Charitable donations play a major role in the provision of hospice and palliative care (HPC) services, most of which are not reimbursed by health insurance programs. A good understanding of the constitution and use of donations is thus conducive to maintaining a high-quality HPC unit. METHODS: The data sources were the publicly available balance sheet, work report, and donor lists of a foundation exclusively supporting one of the best HPC units in Taiwan in the fiscal year of 2017. The analysis included the donation amounts and frequencies by donor type (individual, corporate, and group) and the categories of expenses. RESULTS: The foundation received 3033 donations worth a total of 7.8 million New Taiwan dollars (NTD) (approximately 258 thousand US dollars) in 2017. Two-thirds of the donations were allocated to the provision of direct care services. Of the 3033 donations, only 11 (0.4%) were worth 100 000 NTD or more, while 108 (3.6%) were valued between 10 000 and 99 999 NTD, 1268 (41.8%) were valued between 1000 and 9999 NTD, and 1646 (54.2%) were worth less than 1000 NTD. Of 1051 donors, 974 (92.7%) were individuals, 378 (36.0%) donated more than once, and 106 (10.1%) donated 12 or more times in one year. CONCLUSION: HPC services in Taiwan are sponsored by lots of individuals and small donations. For sustainability of standards-based and quality HPC services, the benevolence of the public should be thus cherished and adequately responded to.

Porcine induced pluripotent stem cell-derived osteoblast-like cells prevent glucocorticoid-induced bone loss in Lanyu pigs.

The application of appropriate animal models and techniques for the study of osteoporosis is important. Lanyu pigs, a local miniature breed, have been widely used in various biomedical studies in Taiwan. This study aimed to induce bone loss in Lanyu pigs and to examine whether porcine induced pluripotent stem cell (piPSC)-derived osteoblast-like cells could recover bone mass of tibiae via local cell transplantation. piPSCs were directed to differentiate into osteoblast-like cells using osteogenic medium, and differentiated cells expressed osteogenic markers and phenotypes. Twenty mature female Lanyu pigs were divided into four groups, including control (C, 1% calcium diet), treatment 1 (T1, ovariectomy + 1% calcium diet), treatment 2 (T2, ovariectomy + 0.5% calcium diet), and treatment 3 (T3, ovariectomy + 0.5% calcium diet + 1 mg/kg of prednisolone) and were subjected to bone loss induction for twelve months. Micro-CT images revealed that the lowest trabecular bone parameters, such as trabecular bone volume, thickness, separation, number, and total porosity, were detected in the T3 group. The lowest proportions of cortical bone in the proximal metaphysis, proximal diaphysis, and distal diaphysis were also found in the T3 group. These results indicate that ovariectomy, calcium restriction, and prednisolone administration can be applied to induce proper bone loss in Lanyu pigs. After bone loss induction, pigs were subjected to cell transplantation in the left tibiae and were maintained for another six months. Results showed that transplanted piPSC-derived osteoblast-like cells significantly improved trabecular bone structures at transplanted sites and maintained cortical bone structures in the proximal metaphysis. In conclusion, the therapeutic potential of piPSC-derived osteoblast-like cells was confirmed via cell transplantation in the left tibiae of Lanyu pigs. These findings reveal the therapeutic potential of piPSCs for glucocorticoid-induced bone loss in pig models.

An iRGD peptide conjugated heparin nanocarrier for gastric cancer therapy.

The cis-diamminedichloroplatinum(ii) (DDP, cisplatin) is an important antitumor drug for the therapy of gastric cancer in clinics, but it is limited by its nonspecific tissue distribution and severe side effects. Here, an integrin targeted drug delivery system iRGD-heparin nanocarrier (iHP) was successfully synthesized. The iHP has several unique properties. First, this nanocarrier has excellent biodegradation due to its heparin biopolymer frame. Second, it is biocompatible because succinic anhydride-modified heparin has no anticoagulant activity and cell toxicity. We proved that from anticoagulant function evaluation and a cytotoxicity test. Third, iRGD was conjugated to the nanoparticles as an integrin-targeting ligand. Our results showed that iHP has precise targeting to integrin-overexpressed human gastric cancer cells MKN-45P in vitro and tumor tissues in vivo. Hence, we synthesized targeted nanoparticles iHP-DDP (iHDDP) and untargeted nanoparticles HP-DDP (HDDP). In our result, iHDDP showed higher antitumor efficacy than HDDP in vitro and in vivo. And in comparison with free DDP, the iHDDP nanoparticle delivery system showed satisfactory antitumor activity of DDP without weight loss or liver and kidney damage in nude mice bearing MKN-45P tumors.

YAP antagonizes innate antiviral immunity and is targeted for lysosomal degradation through IKKɛ-mediated phosphorylation.

The transcription regulator YAP controls organ size by regulating cell growth, proliferation and apoptosis. However, whether YAP has a role in innate antiviral immunity is largely unknown. Here we found that YAP negatively regulated an antiviral immune response. YAP deficiency resulted in enhanced innate immunity, a diminished viral load, and morbidity in vivo. YAP blocked dimerization of the transcription factor IRF3 and impeded translocation of IRF3 to the nucleus after viral infection. Notably, virus-activated kinase IKKɛ phosphorylated YAP at Ser403 and thereby triggered degradation of YAP in lysosomes and, consequently, relief of YAP-mediated inhibition of the cellular antiviral response. These findings not only establish YAP as a modulator of the activation of IRF3 but also identify a previously unknown regulatory mechanism independent of the kinases Hippo and LATS via which YAP is controlled by the innate immune pathway.